ESC GUIDELINES

European Heart Journal (2022) 43, 3997–4126 https://doi.org/10.1093/eurheartj/ehac262

2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC)

Endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)

Authors/Task Force Members: Katja Zeppenfeld[][†] (Chairperson) (Netherlands), Jacob Tfelt-Hansen † (Chairperson) (Denmark), Marta de Riva (Task Force Coordinator) (Netherlands), Bo Gregers Winkel[**] (Task Force Coordinator) (Denmark), Elijah R. Behr (United Kingdom), Nico A. Blom (Netherlands), Philippe Charron (France), Domenico Corrado (Italy), Nikolaos Dagres (Germany), Christian de Chillou (France), Lars Eckardt (Germany), Tim Friede (Germany), Kristina H. Haugaa (Norway), Mélèze Hocini (France), Pier D. Lambiase (United Kingdom), Eloi Marijon (France), Jose L. Merino (Spain), Petr Peichl (Czech Republic), Silvia G. Priori (Italy), Tobias Reichlin (Switzerland), Jeanette Schulz-Menger (Germany), Christian Sticherling (Switzerland), Stylianos Tzeis (Greece), Axel Verstrael (Belgium), Maurizio Volterrani (Italy), and ESC Scientific Document Group

*Corresponding authors: Katja Zeppenfeld, Department of Cardiology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, Netherlands. Tel +31 715262020, E-mail: K.Zeppenfeld@LUMC.nl

Jacob Tfelt-Hansen, The Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. Tel +45 61360399, E-mail: jacob.tfelt@regionh.dk

†The two chairpersons contributed equally to the document and are joint corresponding authors.

• **The two task force Coordinators contributed equally to the document.

Author/task force Member af liations are listed in Author information.

1Representing the Association for European Paediatric and Congenital Cardiology (AEPC).

ESC Clinical Practice Guidelines (CPG) Committee: listed in the Appendix.

ESC subspecialty communities having participated in the development of this document:

Associations: Association for Acute CardioVascular Care (ACVC), Association of Cardiovascular Nursing & Allied Professions (ACNAP), European Association of Cardiovascular Imaging (EACVI), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA), Heart Failure Association (HFA). Working Groups: Cardiac Cellular Electrophysiology, Myocardial and Pericardial Diseases.

Patient Forum

The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (Journals.Permissions@oup.com).

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Document-Reviewers: Maja Cikes (CPG Review Coordinator) (Croatia), Paulus Kirchhof (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Elena Arbelo (Spain), Fernando Arribas (Spain), Riccardo Asteggiano (Italy), Cristina Basso (Italy), Axel Bauer (Austria), Emanuele Bertaglia (Italy), Tor Biering-Sørensen (Denmark), Carina Blomström-Lundqvist (Sweden), Michael A. Borger (Germany), Jelena Čelutkienė (Lithuania), Bernard Cosyns (Belgium), Volkmar Falk (Germany), Laurent Fauchier (France), Bulent Gorenek (Turkey), Sigrun Halvorsen (Norway), Robert Hatala (Slovakia), Hein Heidbuchel (Belgium), Stefan Kaab (Germany), Aleksandra Konradi (Russian Federation), Konstantinos C. Koskinas (Switzerland), Dipak Kotecha (United Kingdom), Ulf Landmesser (Germany), Basil S. Lewis (Israel), Ales Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Andreas Metzner (Germany), Richard Mindham (United Kingdom), Jens Cosedis Nielsen (Denmark), Tone M. Norekvål (Norway), Monica Patten (Germany), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Carol Ann Remme (Netherlands), Ivo Roca-Luque (Spain), Andrea Sarkozy (Belgium), Daniel Scherr (Austria), Marta Sitges (Spain), Rhian M. Touyz (Canada/United Kingdom), Nicolas Van Mieghem (Netherlands), Vedran Velagic (Croatia), Sami Viskin (Israel), and Paul G. A. Volders (Netherlands)

All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/Guidelines

See the European Heart Journal online for supplementary data that includes background information and detailed discussion of the data that have provided the basis of the guidelines.

Click here to access the corresponding ESC CardioMed chapters.

Keywords Guidelines • Anti-arrhythmic drugs • Cardiac magnetic resonance • Cardiomyopathies • Catheter ablation • Chronic coronary artery disease • Genetic testing • Implantable cardioverter defibrillator • Premature ventricular complex • Primary electrical disease • Recommendations • Risk calculator • Risk stratification • Sudden cardiac death • Sudden death • Ventricular arrhythmia • Ventricular fibrillation • Ventricular tachycardia

Table of contents

Disclaimer: The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

© The European Society of Cardiology 2022. All rights reserved. For permissions please e-mail: Journals.Permissions@oup.com

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List of tables

Table 9 Summary of the recommendations for the treatment of patients with frequent idiopathic premature ventricular complexes/ventricular tachycardia or premature ventricular complex-induced cardiomyopathy 4051 Table 10 Modified long QT syndrome diagnostic score 4076

List of figures

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RCM	Restrictive cardiomyopathy
RCT	Randomized control trial
RV	Right ventricular
RVOT	Right ventricle outfow tract
SADS	Sudden arrhythmic death syndrome
SaECG	Signal-averaged ECG
SCA	Sudden cardiac arrest
SCD SD SGLT2 SHD S-ICD SMVT SPTV SQTS STEMI SVT TAVI TdP TOF VA VF VT WCD WPW	Sudden cardiac death Sudden death Sodium–glucose co-transporter 2 Structural heart disease Subcutaneous implantable cardioverter defbrillator Sustained monomorphic ventricular tachycardia Sustained polymorphic ventricular tachycardia Short QT syndrome ST elevation myocardial infarction Supraventricular tachycardia Transcatheter aortic valve implantation Torsades de pointes Tetralogy of Fallot Ventricular arrhythmia Ventricularfbrillation Ventricular tachycardia Wearable cardioverter defbrillator Wolff–Parkinson–White

1. Preamble

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition.

Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, guidelines are not a substitute for the patient’s relationship with their practitioner. The final decisions concerning an individual patient must be made by the responsible health professional(s), based on what they consider to be the most appropriate in the circumstances. These decisions are made in consultation with the patient and caregiver as appropriate.

Guidelines are intended for use by health professionals. To ensure that all users have access to the most recent recommendations, the ESC makes its guidelines freely available. The ESC warns readers that the technical language may be misinterpreted and declines any responsibility in this respect.

A great number of guidelines have been issued in recent years by the ESC. Because of their impact on clinical practice, quality criteria for the development of guidelines have been established to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC website (https://www.escardio.org/Guidelines). The ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated.

In addition to the publication of Clinical Practice Guidelines, the ESC carries out the EURObservational Research Programme of international registries of cardiovascular diseases and interventions that are essential to assess diagnostic/therapeutic processes, use of resources, and adherence to guidelines. These registries aim at providing a better understanding of medical practice in Europe and around the world, based on high-quality data collected during routine clinical practice.

Furthermore, the ESC develops sets of quality indicators (QIs), which are tools to evaluate the level of implementation of the guidelines and may be used by the ESC, hospitals, healthcare providers, and professionals to measure clinical practice, and in educational

Table 1 Classes of recommendations

Classes of recommendations	Class I Class IIa Class II	Evide beneficial, useful, effective. effcacy of the given treatment or procedure. nce and/or general agreement that a given treatment or procedure is Conficting evidence and/or a divergence of opinion about the usefulness/ Is recommended or is indicated Wording to use Defnition W favour of usefulness/effcacy. eight of evidence/opinion is in Should be considered			eit van Amsterdam user on 03 January 2023
	Class IIb	May be considered Usefulness/efficacy is less well
		established by evidence/opinion.
	Class III	Evidence or general agreement that the Is not recommended
		given tr useful/effective, and in some cases eatment or procedure is not may be harmful.	©ESC 2022	© ESC 2022

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Table 2 Levels of evidence

Level of	Data derived from multiple randomized clinical trials
evidence A	or meta-analyses.
Level of evidence B Level of evidence C	Data derived from a single randomized clinical trial or large non-randomized studies. Consensus of opinion of the experts and/or small studies, retrospective studies, registries.	©ESC 2022

programmes, alongside the key messages from the guidelines, to improve quality of care and clinical outcomes.

The Members of this task force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. The selection procedure aimed to ensure that there is a representative mix of members predominantly from across the whole of the ESC region and from relevant ESC Subspecialty Communities. Consideration was given to diversity and inclusion, notably with respect to gender and country of origin. A critical evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk–benefit ratio. The level of evidence and the strength of the recommendation of particular management options were weighed and scored according to predefined scales, as outlined below. The task force followed the ESC voting procedures. All recommendations subject to a vote achieved at least 75% among voting members.

The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. Their declarations of interest were reviewed according to the ESC declaration of interest rules and can be found on the ESC website (http://www.escardio.org/ Guidelines) and have been compiled in a report and published in a supplementary document simultaneously to the guidelines.

This process ensures transparency and prevents potential biases in the development and review processes. Any changes in declarations of interest that arise during the writing period were notified to the ESC and updated. The task force received its entire financial support from the ESC without any involvement from the healthcare industry.

The ESC CPG Committee supervises and coordinates the preparation of new guidelines. The Committee is also responsible for the approval process of these guidelines. The ESC Guidelines undergo extensive review by the CPG Committee and external experts, including a mix of members from across the whole of the ESC region and from relevant ESC Subspecialty Communities and National Cardiac Societies. After appropriate revisions, the guidelines are signed off by all the experts involved in the task force. The finalized document is signed off by the CPG Committee for publication in the

European Heart Journal. The guidelines were developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their writing.

The task of developing ESC Guidelines also includes the creation of educational tools and implementation programmes for the recommendations, including condensed pocket guideline versions, summary slides, summary cards for non-specialists, and an electronic version for digital applications (smartphones, etc.). These versions are abridged and thus, for more detailed information, the user should always access the full-text version of the guidelines, which is freely available via the ESC website and the European Heart Journal. The National Cardiac Societies of the ESC are encouraged to endorse, adopt, translate, and implement all ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations.

Health professionals are encouraged to take the ESC Guidelines fully into account when exercising their clinical judgement, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies. However, the ESC Guidelines do not override in any way whatsoever the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient‘s health condition and in consultation with that patient or the patient’s caregiver where appropriate and/or necessary. It is also the health professional’s responsibility to verify the rules and regulations applicable in each country to drugs and devices at the time of prescription and, where appropriate, to respect the ethical rules of their profession.

Off-label use of medication may be presented in this guideline if sufficient level of evidence shows that it can be considered medically appropriate to a given condition and if patients could benefit from the recommended therapy. However, the final decisions concerning an individual patient must be made by the responsible health professional giving special consideration to:

• (1) the specific situation of the patient. In this respect, it is specified that, unless otherwise provided for by national regulations, off-

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• label use of medication should be limited to situations where it is in the patient’s interest to do so, with regard to the quality, safety, and efficacy of care, and only after the patient has been informed and has provided consent;

• (2) country-specific health regulations, indications by governmental drug regulatory agencies, and the ethical rules to which health professionals are subject, where applicable.

2. Introduction

This document presents an update of the 2015 ESC Guidelines for the management of patients with ventricular arrhythmias (VA) and the prevention of sudden cardiac death (SCD). New insights into the epidemiology of SCD, new evidence on genetics, imaging, and clinical findings for risk stratification for VA and SCD, and advances in diagnostic evaluation and therapeutic strategies made this revision necessary. The committee was composed of 25 members including 23 expert physicians, one methodologist, and one patient representative. Experts were selected to cover all areas of VA and SCD as well as subspecialties of cardiology with the assistance of related ESC working groups.

All 25 members of the task force committee approved the guideline recommendations after an anonymous voting process. Ninety-nine peer reviewers reviewed the document. A systematic literature survey was conducted, after instructions by the methodologist in the group, that led to the incorporation of 1155 references, of which 485 were selected to support the recommendations and further specified in the table of evidence (Supplementary data).

2.1. What is new

The diagnostic and management parts of the guidelines have been adapted to facilitate their use in everyday clinical decision-making.

The first general part has new sections on diagnostic evaluation, including pharmacologic provocative tests, genetic testing, and a systematic work-up of probands and relatives with primary electrical diseases. Comprehensive flowcharts and recommendations for the diagnostic evaluation at first presentation with a VA of patients without a previously known cardiac disease are provided for five frequently encountered clinical scenarios. Practical recommendations for optimization of implantable cardioverter defibrillator (ICD) programming and algorithms for management of patients experiencing regular wide complex tachycardia and electrical storm are presented (Table 3).

Table 3 New sections and concepts

New sections and concepts	Section	© ESC 2022
Provocative diagnostic tests	5.1.3.5
Genetic testing	5.1.4
Diagnostic evaluation atfrst presentation with VA in patients without known cardiac disease	5.2
Management of patients with electrical storm	6.1.3
Special aspects of device therapy	6.2.3

Table 4 New recommendations in 2022

Recommendations	Class
Public basic life support and access to AEDs
It is recommended that public-access defbrillation be available at sites where cardiac arrest is more likely to occur.a	I
Prompt CPR by bystanders is recommended at OHCA.	I
It is recommended to promote community training in basic life support to increase bystander CPR rate and AED use.	I
Mobile phone-based alerting of basic life support-trained bystander volunteers to assist nearby OHCA victims should be considered.	IIa
Treatment of VA. General aspects
DC cardioversion is recommended as thefrst-line treatment for patients presenting with tolerated SMVT provided that the anaesthetic/sedation risk is low.	I
Optimal medical treatment including ACE-I/ARB/ARNIs, MRAs, beta-blockers, and SGLT2 inhibitors is indicated in all heart failure patients with reduced EF.	I
Implantation of a cardioverter defbrillator is only recommended in patients who have an expectation of good-quality survival.1 year.	I
In patients presenting with a haemodynamically tolerated SMVT and known or suspected SHD, intravenous procainamide should be considered.	IIa
In patients presenting with a haemodynamically tolerated SMVT in the absence of an established diagnosis, intravenous amiodarone may be considered.	IIb
In patients with SMVT or SPVT/VF triggered by a PVC with similar morphology and an indication for ICD, catheter ablation may be considered when an ICD is not available, contraindicated for concurrent medical reasons, or declined by the patient.	IIb
The WCD may be considered in the early phase after MI in selected patients.	IIb
Coronary artery disease
In patients with CAD and recurrent, symptomatic SMVT, or ICD shocks for SMVT despite chronic amiodarone therapy, catheter ablation is recommended in preference to escalating AAD therapy.	I
Cardiac stress imaging during physical exercise is recommended in addition to cardiopulmonary exercise test after surgery in patients with anomalous aortic origin of a coronary artery with a history of aborted CA.	I
In SCA survivors with coronary artery spasm, implantation of an ICD should be considered.	IIa
ICD therapy should be considered in patients with CAD, NYHA class I, and LVEF≤30% despite≥3 months of OMT.	IIa
ICD implantation should be considered in patients with CAD, LVEF≤40% despite≥3 months of OMT and NSVT, if they are inducible for SMVT byPES.	IIa
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In patients with CAD and haemodynamically well-tolerated SMVT and LVEF≥40%, catheter ablation in experienced centres should be considered as an alternative to ICD therapy, provided that established endpoints have been reached.b	IIa
Catheter ablation should be considered in patients with CAD and recurrent, symptomatic SMVT, or ICD shocks for SMVT despite beta-blocker or sotalol treatment.	IIa
Idiopathic PVC/VT and PVC-induced cardiomyopathy
Catheter ablation asfrst-line treatment is recommended for symptomatic idiopathic VT/PVCs from the RVOT or the left fascicles.	I
Beta-blockers or non-dihydropyridine CCBs are indicated in symptomatic patients with idiopathic VT/PVCs from an origin other than the RVOT or the left fascicles.	I
In patients with PVCs/VT and a presentation not typical for an idiopathic origin,c CMR should be considered, despite a normal echocardiogram.	IIa
Beta-blockers, non-dihydropyridine CCBs orfecainide should be considered when catheter ablation is not available, not desired, or is particularly risky in symptomatic patients with idiopathic VT/PVCs from the RVOT or the left fascicles.	IIa
Catheter ablation orfecainide should be considered in symptomatic patients with idiopathic VT/PVCs from an origin other than the RVOT or the left fascicles.	IIa
In patients with an unexplained reduced EF and a PVC burden of at least 10%, PVC-induced cardiomyopathy should be considered.	IIa
In patients with suspected PVC-induced cardiomyopathy, CMR should be considered.	IIa
In non-responders to CRT with frequent, predominately monomorphic PVCs limiting optimal biventricular pacing despite pharmacological therapy, catheter ablation or AADs should be considered.	IIa
Catheter ablation may be considered for idiopathic VT/PVCs in asymptomatic patients with repeatedly more than 20% of PVCs per day at follow-up.	IIb
Amiodarone as afrst-line treatment is not recommended in patients with idiopathic VTs/PVCs.	III
DCM/HNDCM
Genetic testing (including at leastLMNA,PLN,RBM20, and FLNCgenes) is recommended in patients with DCM/HNDCM and AV conduction delay at,50 years, or who have a family history of DCM/HNDCM or SCD in afrst-degree relative (at age,50 years).	I
In afrst-degree relative of a DCM/HNDCM patient, an ECG, and an echocardiogram are recommended if: • the index patient was diagnosed,50 years of age or has clinical features suggestive of an inherited cause, or • there is a family history of DCM/HNDCM, or premature unexpected SD.	I
CMR with LGE should be considered in DCM/HNDCM patients for assessingthe aetiologyand the risk of VA/SCD.	IIa

Continued

Genetic testing (including at least LMNA, PLN, RBM20, and FLNC genes) should be considered for risk stratification in patients with apparently sporadic DCM/HNDCM, who IIa present at young age or with signs suspicious for an inherited aetiology. ICD implantation should be considered in DCM/HNDCM patients with an LVEF,50% and ≥2 risk factors (syncope, LGE IIa on CMR, inducible SMVT at PES, pathogenic mutations in LMNA, PLN, FLNC, and RBM20 genes). ICD implantation should be considered in patients with DCM/ IIa HNDCM and haemodynamically tolerated SMVT. In a first-degree relative of a patient with apparently sporadic DCM/HNDCM, an ECG, and an echocardiogram may be IIb considered. Participation in high-intensity exercise including competitive sports is not recommended for individuals with DCM/ III HNDCM and a LMNA mutation. ARVC In patients with suspected ARVC, CMR is recommended. I In patients with a suspected or definite diagnosis of ARVC, I genetic counselling and testing are recommended. ICD implantation should be considered in symptomatic[d] patients with definite ARVC, moderate right or left ventricular IIa dysfunction, and either NSVT or inducibility of SMVT at PES. In ARVC patients with indication for ICDs, a device with the capability of ATP programming for SMVT up to high rates IIa should be considered. Avoidance of high-intensity[e] exercise may be considered in carriers of ARVC-related pathogenic mutations and no IIb phenotype. Beta-blocker therapy may be considered in all patients with a IIb definite diagnosis of ARVC. In patients with ARVC and symptoms highly suspicious for VA, IIb PES may be considered for risk stratification. HCM CMR with LGE is recommended in HCM patients for I diagnostic work-up. Genetic counselling and testing are recommended in HCM I patients. In a first-degree relative of a patient with HCM, ECG, and I echocardiogram are recommended. ICD implantation should be considered in HCM patients aged 16 years or more with an intermediate 5-year risk of SCD (≥4 to,6%)[f], and with (a) significant LGE at CMR (usually ≥15% of IIa LV mass); or (b) LVEF,50%; or (c) abnormal blood pressure response during exercise test[g]; or (d) LV apical aneurysm; or (e) presence of sarcomeric pathogenic mutation. In children,16 years of age with HCM and an estimated 5-year risk of SD ≥6% (based on HCM Risk-Kids score[h]), ICD IIa implantation should be considered. In patients with HCM presenting with haemodynamically IIa tolerated SMVT, ICD implantation should be considered.

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In patients with HCM and recurrent, symptomatic VA, or recurrent symptomatic ICD therapy, AAD treatment should	IIa		Infammatory diseases In patients with haemodynamically not-tolerated sustained VT
be considered.			or VF during the acute phase of myocarditis, ICD implantation	IIa
Participation in high-intensity exercise may be considered for asymptomatic adult HCM patients without risk markers. ICD implantation may be considered in HCM patients aged 16	IIb		before hospital discharge should be considered. In post-myocarditis patients with recurrent, symptomatic VT, AAD treatment should be considered.	IIa
years or more with a low estimated 5-year risk of SCD (,4%),f and with (a) signifcant LGE at CMR (usually≥15% of LV mass); or (b) LVEF,50%; or (c) LV apical aneurysm.	IIb		Catheter ablation, performed in specialized centres, should be considered in post-myocarditis patients with recurrent, symptomatic SMVT, or ICD shocks for SMVT in whom AADs	IIa
Catheter ablation in specialized centres may be considered in selected patients with HCM and recurrent, symptomatic	IIb		are ineffective, not tolerated, or not desired. In patients with haemodynamically tolerated SMVT occurring
SMVT, or ICD shocks for SMVT, in whom AADs are			in the chronic phase of myocarditis, ICD implantation should	IIa
ineffective, contraindicated, or not tolerated.			be considered.
LVNC and RCM			In patients with cardiac sarcoidosis who have an LVEF.35%
In patients with an LVNC cardiomyopathy phenotype based on			but signifcant LGE at CMR after resolution of acute	IIa
CMR or echocardiography, implantation of an ICD for primary	IIa		infammation, ICD implantation should be considered.
prevention of SCD should be considered to follow DCM/			In patients with cardiac sarcoidosis who have an LVEF 35–50%
HNDCM recommendations.			and minor LGE at CMR, after resolution of acute infammation,	IIa
An ICD should be considered in patients with light-chain			PES for risk stratifcation should be considered.
amyloidosis or transthyretin-associated cardiac amyloidosis	IIa		In patients with cardiac sarcoidosis, LVEF 35–50%, and	IIa
and haemodynamically not-tolerated VT.			inducible SMVT at PES, ICD implantation should be considered.
Neuromuscular diseases			In patients with cardiac sarcoidosis and recurrent, symptomatic	IIa
Invasive electrophysiological evaluation is recommended in			VA, AAD treatment should be considered.
patients with myotonic dystrophy and palpitations or syncope	I		Amiodarone should be considered to reduce arrhythmia
suggestive of VA or surviving a CA.			burden in patients with Chagas’cardiomyopathy who present	IIa
ICD implantation is recommended in patients with myotonic dystrophy and SMVT or aborted CA not caused by BBR-VT.	I		with symptomatic PVCs or VT. In patients with Chagas’cardiomyopathy and recurrent,
Invasive electrophysiological evaluation should be considered			symptomatic SMVT, or ICD shocks for SMVT in whom AADs	IIa
in patients with myotonic dystrophy and a sudden increase in	IIa		are ineffective, contraindicated, or not tolerated, catheter
the PR interval or QRS duration.			ablation in specialized centres should be considered.
Invasive electrophysiological evaluation should be considered			In patients with haemodynamically well-tolerated SMVT
in patients with myotonic dystrophy and a PR interval≥240 ms			occurring in the chronic phase of myocarditis, preserved LV
or QRS duration≥120 ms or who are older than 40 years and	IIa		function and a limited scar amenable to ablation, catheter	IIb
have supraventricular arrhythmias, or who are older than 40			ablation may be considered as an alternative to ICD therapy,
years and have signifcant LGE on CMR In myotonic dystrophy patients without AV conduction delay			after discussion with the patient and provided that established endpoints have been reached.b
and a syncope highly suspicious for VA, ICD implantation	IIa		Catheter ablation, in specialized centres, may be considered in
should be considered. In myotonic dystrophy patients with palpitations highly			cardiac sarcoidosis ICD recipients with recurrent, symptomatic SMVT, or ICD shocks for SMVT, in whom AADs are	IIb
suspicious for VA and induction of a non-BBR-VT, ICD	IIa		ineffective, contraindicated, or not tolerated.
implantation should be considered.			Congenital heart disease
In patients with limb-girdle type 1B or Emery–Dreifuss			In patients with CHD presenting with sustained VAs,
muscular dystrophies and indication for pacing, ICD	IIa		evaluation for residual lesions or new structural abnormalities	I
implantation should be considered.			is recommended.
Implantation of an ICD may be considered in patients with			In selected patients with CHD (including atrial baffe repair for
Duchenne/Becker muscular dystrophy and signifcant LGE at	IIb		transposition of the great arteries, Fontan operation, and
CMR.			Ebstein anomaly) presenting with CA, evaluation and	IIa
Implantation of an ICD over a permanent pacemaker may be			treatment of SVT with rapid ventricular conduction should be
considered in myotonic dystrophy patients with additional risk	IIb		considered.
factorsi for VA and SCD.			In patients with repaired TOF undergoing surgical or
In patients with myotonic dystrophy, serial electrophysiological			transcutaneous pulmonary valve replacement, pre-operative
evaluation of AV conduction and arrhythmia induction is not	III		catheter mapping and transection of VT-related anatomical	IIb
recommended without arrhythmia suspicion or progression of			isthmuses before or during the intervention may be
ECG conduction disorders.			considered.
	Continued			Continued

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In patients with repaired TOF with a preserved biventricular function and symptomatic SMVT, catheter ablation or concomitant surgical ablation performed in specialized centres may be considered as an alternative to ICD therapy.	IIb
Idiopathic VF
It is recommended that idiopathic VF is diagnosed in a SCA survivor, preferably with documentation of VF, after exclusion of an underlying structural, channelopathic, metabolic, or toxicological aetiology.	I
Isoproterenol infusion, verapamil, or quinidine for acute treatment of an electrical storm or recurrent ICD discharges should be considered in idiopathic VF.	IIa
Quinidine should be considered for chronic therapy to suppress an electrical storm or recurrent ICD discharges in idiopathic VF.	IIa
Clinical testing (history, ECG, and high precordial lead ECG, exercise test, echocardiogram) offrst-degree family members of idiopathic VF patients may be considered.	IIb
In idiopathic VF patients, genetic testing of genes related to channelopathy and cardiomyopathy may be considered.	IIb
Long QT syndrome
In patients with clinically diagnosed LQTS, genetic testing, and genetic counselling are recommended.	I
Beta-blockers, ideally non-selective beta-blockers (nadolol or propranolol), are recommended in LQTS patients with documented QT interval prolongation, to reduce risk of arrhythmic events.	I
Mexiletine is indicated in LQT3 patients with a prolonged QT interval.	I
In LQTS, it should be considered to calculate the arrhythmic risk before initiation of therapy based on the genotype and the duration of QTc interval.	IIa
ICD implantation may be considered in asymptomatic LQTS patients with high-risk profle (according to the 1-2-3 LQTS Risk calculator) in addition to genotype-specifc medical therapies (mexiletine in LQT3 patients).	IIb
Routine diagnostic testing with epinephrine challenge is not recommended in LQTS.	III
Andersen–Tawil syndrome
Genetic testing is recommended in patients with suspected Andersen–Tawil syndrome.	I
ICD implantation is recommended in patients with Andersen– Tawil syndrome after aborted CA or not-tolerated sustained VT.	I
Andersen–Tawil syndrome should be considered in patients without SHD who present with at least two of the following: • Prominent U waves with or without prolongation of the QT interval • Bidirectional and/or polymorphic PVCs/VT • Dysmorphic features • Periodic paralysis • KCNJ2pathogenic loss of function mutation.	IIa

Beta-blockers and/orfecainide with or without acetazolamide should be considered in patients with Andersen–Tawil syndrome to treat VA.	IIa
An ILR should be considered in patients with Andersen–Tawil syndrome and unexplained syncope.	IIa
ICD implantation may be considered in patients with Andersen–Tawil syndrome who have a history of unexplained syncope or suffer from tolerated sustained VT.	IIb
Brugada syndrome
Genetic testing forSCN5Agene is recommended for probands with BrS.	I
BrS should be considered in patients with no other heart disease and induced type 1 Brugada pattern who have at least one of the following: • Arrhythmic syncope or nocturnal agonal respiration • A family history of BrS • A family history of SD (,45 years old) with a negative autopsy and circumstance suspicious for BrS.	IIa
Implantation of a loop recorder should be considered in BrS patients with an unexplained syncope.	IIa
BrS may be considered as a diagnosis in patients with no other heart disease who exhibit an induced type 1 Brugada ECG.	IIb
PES may be considered in asymptomatic patients with a spontaneous type I BrS ECG.	IIb
Sodium channel blocker test is not recommended in patients with a prior type I Brugada pattern.	III
Catheter ablation in asymptomatic BrS patients is not recommended.	III
Early repolarization syndrome
It is recommended that the ERP is diagnosed as J-point elevation of≥1 mm in two adjacent inferior and/or lateral ECG leads.	I
It is recommended that the ERS is diagnosed in a patient resuscitated from unexplained VF/PVT in the presence of ERP.	I
ICD implantation is recommended in patients with a diagnosis of ERS who have survived a CA.	I
In a SCD victim with a negative autopsy and medical chart review, and an ante-mortem ECG demonstrating the ERP, the diagnosis of ERS should be considered.	IIa
First-degree relatives of ERS patients should be considered for clinical evaluation for ERP with additional high-risk features.j	IIa
ILR should be considered in individuals with ERP and at least one risk featurek or arrhythmic syncope.	IIa
Isoproterenol infusion should be considered for ERS patients with electrical storm.	IIa
Quinidine in addition to an ICD should be considered for recurrent VF in ERS patients.	IIa
PVC ablation should be considered in ERS patients with recurrent VF episodes triggered by a similar PVC non-responsive to medical treatment.	IIa
Genetic testing in ERS patients may be considered.	IIb
ICD implantation or quinidine may be considered in individuals with ERP and arrhythmic syncope and additional risk features.k	IIb

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ICD implantation or quinidine may be considered in asymptomatic individuals who demonstrate a high-risk ERPj in the presence of a family history of unexplained juvenile SD.	IIb
Clinical evaluation is not recommended routinely in asymptomatic subjects with ERP.	III
ICD implantation is not recommended in asymptomatic patients with an isolated ERP.	III
CPVT
Genetic testing and genetic counselling are indicated in patients with clinical suspicion or clinical diagnosis of CPVT.	I
Beta-blockers, ideally non-selective (nadolol or propranolol) are recommended in all patients with a clinical diagnosis of CPVT.	I
Epinephrine or isoproterenol challenge may be considered for the diagnosis of CPVT when an exercise test is not possible.	IIb
Short QT syndrome
Genetic testing is indicated in patients diagnosed with SQTS.	I
SQTS should be considered in the presence of a QTc ≤320 ms.	IIa
SQTS should be considered in the presence of a QTc≥320 ms and≤360 ms and arrhythmic syncope.	IIa
ILR should be considered in young SQTS patients.	IIa
ICD implantation should be considered in SQTS patients with arrhythmic syncope.	IIa
SQTS may be considered in the presence of a QTc ≥320 ms and ≤360 ms and a family history of SD at age,40 years.	IIb
Quinidine may be considered in (a) SQTS patients who qualify for an ICD but present a contraindication to the ICD or refuse it, and (b) asymptomatic SQTS patients and a family history of SCD.	IIb
Isoproterenol may be considered in SQTS patients with an electrical storm.	IIb
Selected populations
It is recommended that athletes diagnosed with a cardiovascular disease associated with SCD are managed according to current guidelines for sports eligibility.	I
Continuation of beta-blockers should be considered during pregnancy in women with ARVC.	IIa
Oral metoprolol, propranolol, or verapamil should be considered for long-term management of idiopathic sustained VT during pregnancy.	IIa
Catheter ablation using non-fuoroscopic mapping systems should be considered, preferably after thefrst trimester, in women with highly symptomatic recurrent SMVT refractory or who are intolerant to AADs.	IIa

Continued

In selected transplanted patients with cardiac allograft vasculopathy or treated rejection, ICD implantation may be considered.	IIb	© ESC 2022
In elderly patients in whom a beneft from the defbrillator is not expected due to the patient’s age and comorbidities, omission of ICD implantation for primary prevention may be considered.	IIb

AAD, anti-arrhythmic drug; ACE-Is, angiotensin-converting enzyme inhibitors; AED, automated external defibrillator; ARBs, angiotensin receptor blockers; ARNIs, angiotensin receptor neprilysin inhibitors; ARVC, arrhythmogenic right ventricular cardiomyopathy; ATP, anti-tachycardia pacing; AV, atrioventricular; BBR-VT, bundle branch re-entry; BrS, Brugada syndrome; CA, cardiac arrest; CAD, coronary artery disease; CCB, calcium channel blocker; CHD, congenital heart disease; CMR, cardiac magnetic resonance; CPR, cardiopulmonary resuscitation; CPVT, catecholaminergic polymorphic ventricular tachycardia; CRT, cardiac resynchronization therapy; DC, direct current; DCM, dilated cardiomyopathy; ECG, electrocardiogram; EF, ejection fraction; ERP, early repolarization pattern; ERS, early repolarization syndrome; HCM, hypertrophic cardiomyopathy; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; LGE, late gadolinium enhancement; LMNA, lamin A/C; LQTS, long QT syndrome; LV, left ventricular; LVEF, left ventricular ejection fraction; LVNC, left ventricular non-compaction; MI, myocardial infarction; MRAs, mineralocorticoid receptor antagonists; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; OHCA, out-of-hospital cardiac arrest; OMT, optimal medical therapy; PES, programmed electrical stimulation; PVC, premature ventricular complex; RCM, restrictive cardiomyopathy; RVOT, right ventricular outflow tract; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SD, sudden death; SGLT2, sodium–glucose co-transporter 2; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; SPVT, sustained polymorphic ventricular tachycardia; SQTS, short QT syndrome; SVT, supraventricular tachycardia; TOF, tetralogy of Fallot; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia; WCD, wearable cardioverter defibrillator. aShopping malls, stadiums, public transport stations, casinos. bVT non-inducibility and elimination of electrograms consistent with conduction delay. cIncluding but not limited to older age, right bundle branch block (RBBB) morphology, SMVT consistent with re-entry.

dPresyncope or palpitations suggestive of VA.

eThe 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease.

fBased on the HCM Risk SCD: https://doc2do.com/hcm/webHCM.html

gDefined as a failure to increase systolic pressure by at least 20 mmHg from rest to peak exercise, or a fall of.20 mmHg from peak pressure. hBased on the HCM Kid Risk score: https://hcmriskkids.org iFactors favouring ICD implantation: Age,5,6,11 CTG expansion,6–9,13,16 SD or family history of SD, ECG conduction abnormalities, PR prolongation, LBBB, atrial arrhythmias, non-sustained VT, LV dysfunction, structural abnormalities in CMR.

jERP high risk features: J waves. 2 mm, dynamic changes in J point and ST morphology. kHigh-risk ERP: family history of unexplained SD,40 years, family history of ERS.

The second part of the guidelines is structured according to disease-specific management, providing a link to the updated

ESC CardioMed chapter for additional content. Risk stratification, SCD prevention, treatment of VA, and management of family members are addressed in a systematic fashion. Indications for cardiac magnetic resonance (CMR) imaging, genetic testing, and updated indications for catheter ablation of ventricular arrhythmias are presented. Flowcharts summarizing the workflow for diagnostic and treatment are provided for the disease entities. The colour-coding of the flowcharts reflects the class of recommendation according to this guideline and other ESC Guidelines.

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Table 5 Changes in recommendations since 2015

	Class	Class
	2015	2022
Coronary artery disease
In patients with syncope and previous STEMI, PES is indicated when syncope remains unexplained after non-invasive evaluation.	IIa	I
Intravenous amiodarone treatment should be considered for patients with recurrent PVT/VF during the acute phase of ACS.	I	IIa
In patients with CAD eligible for ICD implantation, catheter ablation may be considered just before (or immediately after) ICD implantation to decrease subsequent VT burden and ICD shocks.	IIa	IIb
PVC-induced cardiomyopathy
In patients with a cardiomyopathy suspected to be caused by frequent and predominately monomorphic PVCs, catheter ablation is recommended.	IIa	I
DCM/HNDCM
ICD implantation should be considered in patients with DCM/HNDCM, symptomatic heart failure (NYHA class II–III) and LVEF≤35% after≥3 months of OMT.	I	IIa
Catheter ablation in specialized centres should be considered in patients with DCM/HNDCM and recurrent, symptomatic SMVT, or ICD shocks for SMVT, in whom AADs are ineffective, contraindicated, or not tolerated.	IIb	IIa
ARVC
ICD implantation should be considered in patients with defnite ARVC and an arrhythmic syncope.	IIb	IIa
ICD implantation should be considered in patients with defnite ARVC and severe RV or LV systolic dysfunction.	IIb	IIa
Infammatory diseases
In patients with haemodynamically not-tolerated SMVT occurring in the chronic phase of myocarditis, ICD implantation is recommended.	IIa	I
ICD implantation is recommended in patients with cardiac sarcoidosis who have an LVEF≤35%.	IIb	I
ICD implantation is recommended in patients with cardiac sarcoidosis who (1) have documented sustained VT, or (2) aborted CA.	IIb	I
In patients with cardiac sarcoidosis who have an indication for permanent cardiac pacing related to high-degree AV block, ICD implantation should be considered, regardless of LVEF.	IIb	IIa
In patients with Chagas’cardiomyopathy and symptomatic VT in whom AADs (amiodarone and beta-blockers) are ineffective or not tolerated, ICD implantation maybe considered.	IIa	IIb

Continued

CHD	CHD	IIb IIa I IIa IIa IIa IIa © ESC 2022
In patients after repair of TOF without arrhythmia symptoms, but with a combination of other risk factors,a electrophysiologic evaluation, including PES, may be considered.	IIa	IIb
In patients with CHD and recurrent, symptomatic SMVT, or ICD shocks for SMVT not manageable by medical therapy or ICD reprogramming, catheter ablation performed in specialized centres should be considered.	I	IIa
Primary electrical disease and selected populations
ICD implantation is recommended in patients with LQTS who are symptomaticb while receiving beta-blockers and genotype-specifc therapies.	IIa	I
ICD implantation should be considered in patients with CPVT who experience arrhythmic syncope and/ or documented bidirectional/PVT while on the highest tolerated beta-blocker dose and onfecainide.	I	IIa
Pre-participation cardiovascular evaluation of competitive athletes should be considered.	I	IIa
Catheter ablation of triggering PVCs and/or RVOT epicardial substrate should be considered in BrS patients with recurrent appropriate ICD shocks refractory to drug therapy.	IIb	IIa
LCSD should be considered in patients with diagnosis of CPVT when the combination of beta-blockers and fecainide at therapeutic dosage are either not effective, not tolerated, or contraindicated.	IIb	IIa

AAD, anti-arrhythmic drug; ACS, acute coronary syndrome; ARVC, arrhythmogenic right ventricular cardiomyopathy; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CAD, coronary artery disease; CHD, congenital heart disease; CPVT, catecholaminergic polymorphic ventricular tachycardia; DCM, dilated cardiomyopathy; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; LCSD, left cardiac sympathetic denervation; LQTS, long QT syndrome; LV, left ventricle; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; OMT, optimal medical treatment; PES, programmed electrical stimulation; PVC, premature ventricular complex; PVT, polymorphic ventricular tachycardia; RV, right ventricle; RVOT, right ventricular outflow tract; SMVT, sustained monomorphic ventricular tachycardia; STEMI, ST elevation myocardial infarction; TdP, torsade de pointes; TOF, tetralogy of Fallot; VF, ventricular fibrillation; VT, ventricular tachycardia. aOther risk factors include moderate RV or LV dysfunction, extensive RV scarring on CMR, QRS duration ≥180 ms, and severe QRS fragmentation. bArrhythmic syncope or haemodynamically not-tolerated VA.

Another novel concept of this document is the table of evidence (see Supplementary data). The trials and studies that have been selected to support a recommendation are systematically described in the table of evidence after careful review of the available data and the applied methodology, prioritizing papers published after 2015. Recommendations with level of evidence C that are not accompanied by a reference are supported by this panel of experts. To assist physicians in their daily clinical practice, diagnostic and therapeutic procedures with promising usefulness, typically classified as class IIb, but for which evidence is limited and difficult to collect in the near future, the related recommendations are not only described in the narratives but are listed in the table of recommendation.

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3. De nitions

3.1. Ventricular arrhythmia subtypes

Premature ventricular complex (PVC): Premature occurrence of an abnormal QRS complex (duration typically ≥120 ms, corresponding T-wave typically broad and in the opposite direction of the major QRS deflection, no preceding P-wave).

Unifocal or monomorphic PVCs: PVCs with a single QRS morphology. Multifocal, multiform, or polymorphic PVCs: PVCs with different QRS morphologies.

Short-coupled PVC: A PVC that interrupts the T-wave of the preceding conducted beat.

Ventricular tachycardia (VT): ≥3 consecutive beats with a rate.100 b.p.m. originating from the ventricles, independent from atrial and atrioventricular (AV) nodal conduction.

Non-sustained ventricular tachycardia (NSVT): Run of consecutive ventricular beats persisting for 3 beats to 30 s.

Monomorphic ventricular tachycardia (MVT): Same QRS morphology from beat to beat.

Polymorphic ventricular tachycardia (PVT): Continually changing QRS morphology.

Sustained monomorphic/polymorphic ventricular tachycardia (SMVT/ SPVT): Continuous VT for at least 30 s, or which requires an intervention for termination.

Bidirectional ventricular tachycardia: Beat to beat alternation of the frontal QRS axis (e.g. in catecholaminergic polymorphic ventricular tachycardia [CPVT], Andersen–Tawil, digoxin toxicity, acute myocarditis).

Torsades de pointes ventricular tachycardia (TdP): Subtype of a polymorphic VT in the context of QT prolongation with continually changing QRS complexes that appear to spiral around the baseline of the electrocardiogram (ECG) lead in a sinusoidal pattern.

Ventricular fibrillation (VF): A chaotic rhythm with undulations that are irregular in timing and morphology, without discrete QRS complexes on the surface ECG.

Electrical storm: VA that occurs 3 or more times within 24 h (separated by at least 5 min), each requiring termination by an intervention.

Incessant VT: Continuous sustained VT that recurs promptly despite repeated intervention for termination over several hours.

3.2. Sudden cardiac death

Sudden cardiac arrest (SCA): Sudden cessation of normal cardiac activity with haemodynamic collapse.

Sudden cardiac death (SCD): Sudden natural death presumed to be of cardiac cause that occurs within 1 h of onset of symptoms in witnessed cases, and within 24 h of last being seen alive when it is unwitnessed. SCD in autopsied cases is defined as the natural unexpected death of unknown or cardiac cause.

Sudden unexplained death: Unexplained sudden death occurring in an individual older than 1 year.

Sudden infant death syndrome (SIDS): Unexplained sudden death occurring in an individual younger than 1 year with negative pathological and toxicological assessment and negative forensic examination of the circumstances of death.

Sudden arrhythmic death syndrome (SADS): Unexplained sudden death occurring in an individual older than 1 year with negative pathological and toxicological assessment. Note: Synonymous with ‘ ’ autopsy-negative sudden unexplained death.

3.3. Syncope

Unexplained syncope: Transient loss of consciousness due to cerebral hypoperfusion, characterized by a rapid onset, short duration, and spontaneous complete recovery, but unexplained after conventional workup. Work-up and differential diagnosis are provided in the 2018 ESC Guidelines for the diagnosis and management of syncope.

Arrhythmic syncope: as above, but highly suspicious for intermittent bradycardia, rapid supraventricular tachycardia (SVT), or VA.

3.4. Specialized centres

Multidisciplinary teams: A multidisciplinary team across specialties is characterized by open communication, positive management and leadership, appropriate resources, and a mix of skills. Decision-making should be shared in the team.

Specialized centre for catheter ablation of VA: Patient and procedural complexity vary widely. Some patients require a more experienced operator and a centre with more capabilities, which is more likely in patients with a non-ischaemic aetiology. A specialized centre has at least one operator with appropriate experience in interventions that may be required for a successful procedure (e.g. percutaneous epicardial access). The centre performs catheter ablation of VT in structural heart disease (SHD) on a regular basis. In addition, the centre has the required resources to manage medical conditions, comorbidities, and potential complications in patients undergoing complex VA ablation; this includes interventional cardiology expertise, acute placement of mechanical circulatory assist devices, and cardiothoracic surgical back-up. Considering the variable availability across European countries, it is preferable to treat complex patients in the most experienced centre within reasonable distance.

3.5. Genetics

Pathogenic variant and likely pathogenic variant: The American College of Medical Genetics has provided a framework for the interpretation of disease causation by genetic variants standardized into classes. The genetic variants most likely to cause an associated disease are termed V, ‘pathogenic’, and IV, ‘likely pathogenic’.

Mutation: This term is used in this document to mean a Class IV or V variant.

Variant of uncertain significance: A change in a gene’s deoxyribonucleic acid (DNA) sequence that has an unknown effect on a person’s health.

4. Epidemiology of sudden cardiac death, public awareness, and risk stratification

4.1. Incidence of sudden cardiac death

SCD accounts for approximately 50% of all cardiovascular deaths, with up to 50% being the first manifestation of cardiac disease. Ideally, cases suspicious of SCD should be identified from multiple

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sources and undergo autopsy, which is required to reliably exclude non-cardiac causes of sudden death (SD).

The incidence of SCD increases markedly with age. With a very low incidence during infancy and childhood (1 per 100 000 personyears), the incidence is approximately 50 per 100 000 personyears in middle-aged individuals (in the fifth to sixth decades of life). In the eighth decade of life, it reaches an annual incidence of at least 200 per 100 000 person-years. At any age, males have higher SCD rates compared with females, even after adjustment for risk factors of coronary artery disease (CAD). Ethnic background also seems to have large effects. It is estimated that 10–20% of all deaths in Europe are SCD. Approximately 300 000 people in Europe have out-of-hospital cardiac arrest (OHCA) treated by emergency medical systems every year.

In the Western world, the epidemiology of SCD is closely related to CAD, which is responsible for up to 75–80% of SCD cases. While the prevalence of CAD has not decreased, there has been a significant decline in mortality due to CAD. Reports show that the incidence of SCD is declining, but the risk of SCD as a proportion of the overall cardiovascular deaths may have increased.

Although regular physical activity benefits cardiovascular health, sport, particularly when practiced vigorously, has been shown to be associated with SCD during or shortly after exercise in selected populations. Reports have suggested that the majority of sportsrelated SCD occurs in a recreational rather than competitive setting, especially among middle-aged male participants, suggesting that CAD is the most common underlying cause.

from the general population at risk of SCD as their first cardiac event. Models for novel SCD risk stratification in the general population have recently been proposed. There are no clear data supporting the benefit of mass screening programs in the general population for preventing SCD.

For decades, investigators have envisioned a broad range of ‘indicators’ for SCD, especially occurring in the setting of CAD. Several non-invasive markers of risk have been proposed (including late potentials, heart rate variability, periodic repolarization dynamics, and baroreflex sensitivity). Despite the promising outcomes of initial studies, however, these ‘predictors’ have not yet influenced clinical practice. Left ventricular ejection fraction (LVEF) is only used, often in combination with New York Heart Association (NYHA) class, for primary prevention indication of an ICD in the setting of chronic CAD and dilated cardiomyopathy (DCM). Risk stratification schemes and calculators have been developed for inheritable arrhythmogenic diseases, such as hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and lamin A/C (LMNA) cardiomyopathy.

What is considered low, intermediate, or high risk will depend on the type of event (e.g. fatal or not) and the risk of an event in the background population. For instance, mortality depends on age, sex, and other risk factors including comorbidities. The situation is further complicated when considering a specific type of death, e.g. SCD. Then non-SCD deaths are competing events (or competing risks) to SCD in the sense that their occurrence prevents the observation of SCD, and may make interventions to prevent SCD, such as an ICD, of limited benefit.

4.2. Causes of sudden cardiac death in

different age groups

Cardiac diseases associated with SCD vary depending on the individual’s age. In the young there is a predominance of primary electric diseases and cardiomyopathies, as well as myocarditis, and coronary anomalies. However, half of SCD cases during the fourth decade are related to CAD, especially acute coronary syndrome (ACS).

In older populations, chronic structural diseases predominate (CAD either through acute coronary events or chronic coronary stenoses, valvular heart diseases, and heart failure), while potentially inherited electrical diseases or structural non-ischaemic diseases may cause more than 50% of SCD in individuals under the age of 50 years.

Age distribution at presentation with ventricular arrhythmias and sudden cardiac death, dominant arrhythmia subtypes, triggers, genetic factors, and gender associated with increased risk for ventricular arrhythmias in selected primary electrical and structural heart diseases are presented in Figure 1.

4.3. Population vs. individual risk prediction

In the general population (individuals without known heart disease), - the most effective approach for preventing SCD resides in quantifi cation of the individual risk of developing CAD based on risk score charts. Several studies have provided evidence that there is a genetic predisposition to die suddenly during acute ischaemia. The goal would be to identify the relatively small, high-risk subgroups

4.4. Risk calculators for sudden cardiac death and review of the methodology

A number of risk calculators for SCD have been proposed for adult and paediatric populations. The field of prediction modelling has evolved over the past decades, establishing standards for the development, validation (internal and external), and reporting of prediction models in SCD. In addition to discrimination measures such as the c-index, measures of calibration such as the calibration slope have recently received more attention because it is not only important to distinguish patients with higher risks from those with lower risks but also to obtain a robust quantification of the risk itself from the risk calculators. Typical shortcomings in the development and validation of risk calculators include, but are not limited to, the use of historic samples not representative of contemporary patient cohorts, missing values, composite outcomes with composite events of different clinical importance, lack of external validation, and missing calibration. In this document different cut-off for 5 years risk of SCD/VA is used for indication of ICD. Each cut-off was chosen by the original authors and the task force group considering the competing risk, the outcome measured (SCD vs VA) and the robustness of each risk calculator.

4.5. Awareness and intervention: public basic life support, and access to automated external defibrillators

Survival rate remains strikingly low after OHCA, although major regional disparities have been described. Early implementation of

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----- Start of picture text ----- Genetic risks and triggers Age at Dominant subtype for VA/SCD VA/SCD of VA (%) 10 20 30 40 50 60 70 80 0 50 100 PVT CPVT MVT PVT LQT MVT PVT BrS MVT PVT ACS MVT Sarcoid PVT MVT PVT HCM MVT PVT DCM MVT PVT ARVC MVT PVT rTOF MVT chronic PVT CAD MVT ----- End of picture text -----

Figure 1 Central figure. Genetic risk for VA/SCD, typical triggers for VA/SCD, age at presentation with VA/SCD, sex predominance, and typical VA (PVT/VF vs. MVT) in different diseases associated with VA/SCD. ACS, acute coronary syndrome; ARVC, arrhythmogenic right ventricular cardiomyopathy; BrS, Brugada syndrome; CAD, coronary artery disease; CPVT, catecholaminergic polymorphic ventricular tachycardia; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LQT, long QT syndrome; MVT, monomorphic ventricular tachycardia; PVT, polymorphic ventricular tachycardia; rTOF, repaired tetralogy of Fallot; SCD, sudden cardiac death; VA, ventricular arrhythmia; VF, ventricular fibrillation.

resuscitative interventions, especially prior to emergency medical system arrival, has been identified as key elements to improve survival. Bystander cardiopulmonary resuscitation (CPR) and use of public automated external defibrillators (AEDs) have demonstrated improvement of neurological and functional outcome as well as survival of OHCA patients. Data support the need for

increased availability of public access defibrillators and community training in basic life support, preferably initiated in childhood and repetitive. Finally, dispatch of basic life support-trained volunteers, through specific mobile apps networks, has been shown to increase the rate of bystander-initiated CPR, and as a result, greatly reduces the resuscitation-free interval and improves the outcome of

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OHCA victims. Education of public officials and community members regarding the importance of increasing rates of bystander CPR and promoting the use of early defibrillation by lay and professional rescuers is critical to increasing survival rates.

b-type-natriuretic peptide as a method to select the need for an ICD.

5.1.3. Non-invasive and invasive tests

5.1.3.1. Electrocardiogram and ambulatory electrocardiographic monitoring

Recommendation Table 1 — Recommendations for public basic life support and access to automated external defibrillators

Recommendations	Classa	Levelb	© ESC 2022
It is recommended that public access defbrillation be available at sites where cardiac arrest is more likely to occur.c,90–92	I	B
Prompt CPR by bystanders is recommended at OHCA.93–95	I	B
It is recommended to promote community training in basic life support to increase bystander CPR rate and AED use.93,97,104	I	B
Mobile phone-based alerting of basic life support-trained bystander volunteers to assist nearby OHCA victims should be considered.101–103,105	IIa	B

AED, automated external defibrillator; CPR, cardiopulmonary resuscitation; OHCA, out-of-hospital cardiac arrest. aClass of recommendation. bLevel of evidence. cShopping centres, stadiums, public transport stations, casinos.

5. Evaluation and treatment. General aspects

5.1. Diagnostic tools

5.1.1. History and physical examination

History should focus on ‘red flags’, including features of arrhythmic syncope, e.g. absence of vagal prodrome, and family history of premature or SCD including, e.g. drowning or car accident in long QT syndrome (LQTS), and CPVT. Subtle features to suggest inherited causes include a family history of epilepsy, sudden infant death syndrome, deafness (LQTS), heart failure, or pacemaker implantation at,50 years old. Features of diseases related to pro-arrhythmic conditions include mid-systolic click in mitral valve prolapse (MVP) and outflow tract murmurs with Valsalva in HCM. Specific skin features may be relevant, e.g. Lupus pernio, erythema nodosum in sarcoidosis, angiokeratoma in Fabry’s disease, xanthelasma/xanthoma, and palmoplantar keratosis in ARVC.

5.1.2. Laboratory testing

Natriuretic peptides (b-type-natriuretic peptide, or N-terminal pro-b-type-natriuretic peptide) may have a role in the identification of individuals at increased risk of SCD in the general population or in patients with CAD. There is not sufficient evidence to use

The 12-lead ECG is an important tool for the diagnosis of underlying disease, for risk stratification in selected populations, and for the diagnosis of the VA subtype, if captured. Documentation of arrhythmias related to symptoms is clinically pivotal but may be challenging with sporadic events. The type of ECG-monitoring device and the recording time should therefore match the frequency of clinical events. Monitoring over a period of 24–48 h (typically ‘Holter recording’) is appropriate for daily arrhythmias, while intermittent monitoring over a longer period, with patient-activated ECG recorders (or mobile-health/smartphones), should be preferred for infrequent events. Implantable loop recorders (ILR) can be useful in diagnosing arrhythmias in patients with potentially life-threatening symptoms, such as unexplained syncope.

5.1.3.2. Signal-averaged electrocardiogram

Signal-averaged electrocardiogram (SaECG) can detect very low amplitude signals (‘late potentials’) in the terminal QRS segment using three time-domain measurements: QRS duration, low-amplitude (,40 µV) signal duration and root mean square voltage of terminal 40 ms QRS. Abnormalities in the SaECG can also be assessed by frequency-domain analysis. SaECG can contribute to the diagnosis of ARVC.

5.1.3.3. Exercise testing

Exercise testing is useful for the diagnosis and for evaluating response to therapy in patients with suspected/proven adrenergic-dependent rhythm disturbances, such as exercise-induced idiopathic MVT, PVT, or bidirectional VT in CPVT. The 4-minute recovery QTc after exercise testing can contribute to the diagnosis LQTS.

5.1.3.4. Imaging

Imaging is crucial to assess cardiac function and detect cardiomyopathies ( ESC CardioMed chapter 10). A negative imaging study supports primary electrical disease in a patient with VA. Echocardiography is a readily available and first-line diagnostic and risk stratification tool for valve diseases, CAD and DCM, HCM, ARVC, and left ventricular non-compaction (LVNC). Echocardiographic strainrate imaging allows differentiation between active and passive movement of myocardial segments and early detection of myocardial dysfunction. Wall motion abnormalities can indicate previous infarcts, cardiomyopathies, or inflammatory disease. Global longitudinal strain is a robust measure of left ventricular (LV) function and can detect subtle changes in LV function while LVEF is still preserved. Strain imaging can assess mechanical dispersion reflecting inhomogeneous contraction that could be associated with increased risk of VA.

CMR currently provides the most accurate and reproducible measurement of atrial, biventricular global and regional systolic function, and can detect myocardial oedema, fibrosis, infiltration, and

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perfusion defects ( ESC CardioMed chapter 11.4). CMR is more sensitive than echocardiography to diagnose ARVC, is diagnostic in LVNC, and can detect apical aneurysms in HCM. Fibrosis detection by late gadolinium enhancement (LGE) contributes to VA risk stratification in HCM, DCM, and potentially in mitral valve prolapse arrhythmic syndrome. Novel myocardial mapping techniques can detect diffuse fibrosis and can suggest the aetiology of left ventricular hypertrophy (LVH) for specific therapy guiding, e.g. Fabry disease and amyloidosis. The prognostic value remains to be evaluated.

Cardiac imaging by computed tomography (CT) has the advantage of a high spatial resolution ( ESC CardioMed chapter 12.1). ECG synchronization, additional breath-hold sequences, and betablocker to lower the heart rate improve the quality. Radiation exposure is in the range of an invasive coronary angiogram (CAG). Coronary computed tomography angiography (CTA) is the preferred method to rule out coronary artery stenosis in patients with low probability of CAD. The quality of almost all image modalities is influenced by the presence of frequent PVCs.

5.1.3.5. Provocative diagnostic tests

These are summarized in Table 6. Common tests performed are sodium channel blocker testing for Brugada syndrome (BrS) and adenosine test to exclude latent pre-excitation. Epinephrine challenge may be useful in CPVT when exercise cannot be performed. Epinephrine test is not recommended for LQTS due to the high false positive rate and utility of exercise testing. Coronary vasospasm as a cause of VF in the absence of obstructive coronary diseases/cardiomyopathy can be tested with incremental intracoronary doses of acetylcholine/ergonovine.

5.1.3.6. Electrophysiological study

Electrophysiological studies including measurement of baseline inter– – vals (e.g. atrial His interval [AH] and His ventricular interval [HV]), programmed electrical stimulation (PES), and electroanatomical mapping can be used for diagnostic purposes and to guide therapy. The yield of PES varies with the underlying cardiac condition and its severity, the presence or absence of spontaneous VT, concomitant drug therapy, stimulation protocol, and site(s) of stimulation. Typical protocols include stimulation from 2 right ventricular – (RV) sites with 2 3 basic drive cycle lengths, introduction of 3 extrastimuli, and isoprenaline administration.

In the current era, PES is mainly employed to confirm the diagnosis of VT and induce mappable VAs with non-inducibility being an ablation endpoint. Patients with heart failure and LVEF ≤35% generally will have an indication for an ICD; therefore, VT/VF induction before implantation is not necessary. In patients with SHD and mildly reduced or preserved LVEF who present with unexplained syncope, induction of SMVT with PES can be helpful to identify the underlying cause and to predict subsequent events. PVT/VF induction in SHD is in general considered as a non-specific finding.

In primary electrical diseases, PES is not of prognostic value, although there is some evidence to consider its use in BrS. Invasive electrophysiological evaluation can have important clinical implications in patients with myotonic dystrophy.

With advances in high-density mapping, voltage mapping, conduction/repolarisation metrics, and electrogram fractionation can be employed to identify ablation targets, or to diagnose cardiomyopathic disease. Endocardial mapping may be helpful in the differentiation of ARVC from benign outflow tract VT and for targeting biopsy in suspected myocarditis, ARVC, and sarcoidosis cases.

5.1.4. Genetic testing

Massive parallel or next-generation sequencing has led to increasing availability of genetic testing at reduced cost. Most diagnostic cardiac genetic testing employs large gene panels determined by associations with disease generated by prior research, i.e. candidate genes. Many previous gene associations have, however, been challenged for their diagnostic utility. Therefore, it is not recommended to include questionable genes in routine diagnostic panels. Genome-wide association studies have identified that common genetic variation single nucleotide polymorphisms can cause or modify phenotypes in BrS, LQTS, HCM, and DCM. Polygenic risk scores, measures derived from the cumulative effects of these single nucleotide polymorphisms, may therefore play a role in diagnosis and prognostication in these conditions in the future.

Sequencing produces digital data that require subsequent bioinformatic analysis, permitting accurate ascertainment of most DNA alterations affecting the coding frame of each gene. The most common findings are single nucleotide variants causing simple amino acid substitutions (missense), premature terminations, or splicing abnormalities. Insertions and/or deletions are rarer. The clinical importance of most non-coding variants is still to be determined.

A framework for the interpretation of disease causation by genetic variants has standardized adjudication into five classes: V ‘pathogenic’; IV ‘likely pathogenic’; III ‘variant of uncertain significance’; II ‘likely benign’; and I ‘benign’. A combination of evidence is employed: gene– disease association; presence of a variant in healthy and/or diseased populations; in silico data; in vitro and in vivo functional data; and family segregation data.

A mutation (Class IV or V variant) can be used immediately either for confirmation of diagnosis in probands (the first affected family member), or for initial diagnosis of relatives and may help to guide therapy and/or prognosis. Periodic reassessment of all class IV and III variants is indicated.

Pre-implantation genetic testing is an early form of pre-natal genetic diagnosis. Genetic diagnoses of in vitro fertilized embryos are identified by biopsies, thereby allowing transfer of genetically normal embryos into the uterus. If the technique is available, it is important to provide information to patients with monogenic heart diseases in child-bearing age. The legislation for pre-implantation genetic testing varies in different countries and strategies differ.

Genetic and clinical testing should be undertaken only by multidisciplinary teams including professionals with skills to counsel on the implications and the uncertainty of results and experienced cardiologists able to direct testing to the correct phenotype. A negative result does not exclude a diagnosis and should not be used for this purpose. A framework for genetic and other clinical diagnostic tests for primary electrical diseases based on evidence where available has been provided in Table 7.

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Ref	136,138,139	140	141	142	Continued
Location	Cath lab or outpatient testing location with full resuscitation equipment.	Same as ajmaline.	Same as ajmaline.	Cath lab.
Observation times	30 min if negative test; 4 h if positive test.	4 h if negative test; 24 h if positive test.	30 min.	Normal post-procedure observational time.
Criteria to stop test, counselling and management	VT/VF, Type 1 BrS ECG, PVCs, QRS widening.150%. If VT/VF, administer iv isoprenaline, iv sodium bicarbonate.	Same as ajmaline.	Systolic blood pressure≥ 200 mmHg, non-sustained VT or PVT,.10 PVCs /min, T-wave alternans, or patient intolerance. If symptoms persist after discontinuation, iv metoprolol 2.5–5 mg over 1 min.	Temporary wire for back-up pacing. Risk of cardiogenic shock.
Contraindications	Type I BrS ECG, HF. Precaution if evidence of conduction disease (consider temporary pacing wire).	Same as ajmaline.	QTc prolongation≥480 ms.	Left main stenosis.50%, 3-vessel disease, 2-vessel disease with total occlusion, NYHA III/IV HF, renal failure, severe bronchial asthma.
Positive test	BrS type 1 ECG.	Same as ajmaline.	≥3 beats of PVT or bidirectional VT.	Coronary artery spasm visualized during procedure.
Protocols Dose/infusion rate/duration	1 mg/kg over 5–10 min (maximum dose 100 mg) or 1 mg/kg at 10 mg/min. Record in standard and high precordial leads over 30 min.	2 mg/kg over 10 min (maximum dose 150 mg). Record in standard and high precordial leads over 30 min.	Rest 10 min. Start at 0.025 µg/ kg/ min for 10 min increase sequentially to 0.05, 0.1 and 0.2 µg/ kg/min in 5 min steps.	Intracoronary injection: RCA: 20 and 50 µg. LCA: 20, 50, and 100 µg over 20 s..3-min intervals between injections. Maximal dose of 50 µg in the RCA and 100 µg in the LCA.
Indication	Family history of BrS or SADS. Resuscitated CA without SHD.	Same as ajmaline.	CPVT and resuscitated CA with or without SHD when exercise test not feasible. Family history of SADS.	Suspicion of coronary vasospasm.
Diagnostic test	Ajmaline	Flecainide	Epinephrine	Acetylcholine

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	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Table 7 Genetic tests and suggested work-up of probands and relatives with primary electrical diseases LQTS BrS CPVT Idiopathic VF ERS Genetic test Class Ia Class I Class Ia Class IIb Class IIb Proband Initial clinical test Cornerstone for diagnosis ECG Exercise test ECG and high precordial lead ECG Sodium channel blockers provocative testc Exercise test SeeSection 5.2.3, scenario 3 ECG Other tests/processes Exclude acquired LQTS Exclude phenocopyb Exclude phenocopyb/SHD Holter Echocardiography Follow-up 1–3 years dependent on level of risk Relatives Clinical screening ECG Exercise test (when feasible) From birth ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181 ECG Exercise test From birth ECG and high precordial lead ECGs Exercise test Echocardiogram182 ECG Echocardiogram Follow-up Positive phenotype and/or Class IV/V variant 1–3 years dependent on level of risk 2022 Adenosine Exclude latent pre-excitation. 6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs. Identifcation of accessory pathway. Asthma, sinus node disease, allergy to adenosine. Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline. 5 min. Same as ajmaline. 144 © ESC 2022 AF, atrialfbrillation; AV, atrioventricular; BrS, Brugada syndrome; CA, cardiac arrest; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; HF, heart failure; LCA, left coronary artery; NYHA, New York Heart Association; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RCA, right coronary artery; SADS, sudden arrhythmic death syndrome; SHD, structural heart disease; VF, ventricular fbrillation; VT, ventricular tachycardia.	Negative phenotype and no Class IV/V variant Discharge © ESC BrS, Brugada syndrome; CPVT, catecholaminergic polymorphic ventricular tachycardia; ECG, electrocardiogram; ERS, early repolarization syndrome; LQTS, long QT syndrome; VF, ventricularfbrillation. aIncluding neonatal genetic testing. bA phenocopy has characteristics of a genetic disease but is produced environmentally. cNot in case of a documented type 1 Brugada pattern. Downloaded from https://academic.oup.com/eurheartj/article/43/40/3997/6675633 by Universiteit van Amsterdam user on 03 January 2023
143	144	ERS	Class IIb	ECG	Holter Echocardiography	1–3 years dependent on level of risk	ECG Echocardiogram	1–3 years dependent on level of risk	Discharge
Cath lab.	Same as ajmaline.
		Idiopathic VF	Class IIb	SeeSection 5.2.3, scenario 3			ECG and high precordial lead ECGs Exercise test Echocardiogram182
Same as acetylcholine.	5 min.
		CPVT	Class Ia	Exercise test	Exclude phenocopyb/SHD		ECG Exercise test From birth
Temporary wire should be placed for back-up pacing. Risk of cardiogenic shock.	Side effects: Bronchospasm, bradycardia, asystole, AF, seizure. Antagonist: theophylline.
		BrS	Class I	ECG and high precordial lead ECG Sodium channel blockers provocative testc	Exclude phenocopyb		ECG and high precordial lead ECGs: start at 10 years Sodium channel blockers provocative testc: start.16 years unless clinically indicated180,181
Left main stenosis.50%, 3-vessel disease, 2-vessel disease with total occlusion, NYHA III/V HF, renal failure.	Asthma, sinus node disease, allergy to adenosine.
Same as acetylcholine	Identifcation of accessory pathway.
		LQTS	Class Ia	ECG Exercise test	Exclude acquired LQTS		ECG Exercise test (when feasible) From birth
Intracoronary stepwise injection: RCA (20–60 mg) LCA (20–60 mg) over a period of 2–5 min.	6, 12, 18 mg boluses up to maximum dose 24 mg or until AV block or pre-excitation occurs.
			Genetic test	Cornerstone for diagnosis	Other tests/processes			Positive phenotype and/or Class IV/V variant	Negative phenotype and no Class IV/V variant
Same as acetylcholine.	Exclude latent pre-excitation.
				Initial clinical test		Follow-up	Clinical screening	Follow-up
Ergonovine	Adenosine
				Proband			Relatives

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Recommendation Table 2 — Recommendations for genetic testing

Recommendations	Classa	Levelb	© ESC 2022
Genetic testing is recommended when a condition is diagnosed in a living or deceased individual with a likely genetic basis and a risk of VA and SCD.56,183	I	B
When a putative causative variant isfrst identifed, evaluation for pathogenicity is recommended using an internationally accepted framework.176	I	C
When a Class IV or Class V variant has been identifed in a living or deceased individual with a condition that carries a risk of VA and SCD, genetic testing offrst-degree and symptomatic relatives and obligate carriers is recommended.	I	C
It is recommended that genetic testing and counselling on its potential consequences should be undertaken by an expert multidisciplinary team.179	I	C
It is recommended that Class III (variants of uncertain signifcance) and Class IV variants should be evaluated for segregation in families where possible, and the variant re-evaluated periodically.	I	C
It is not recommended to undertake genetic testing in index patients with insuffcient evidence of a genetic disease.	III	C

SCD, sudden cardiac death; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence.

5.2. Diagnostic evaluation at first presentation with ventricular arrhythmia in patients without known cardiac disease

VA and (aborted) SCD are common first manifestations of a previously not known cardiac condition. A comprehensive diagnostic evaluation is provided for five frequently encountered scenarios.

5.2.1. Scenario 1: Incidental finding of a non-sustained ventricular tachycardia

An algorithm for the evaluation of patients presenting with an incidental finding of NSVT is presented in Figure 2.

Incidental NSVT is a common finding during routine cardiological evaluation (e.g. for non-cardiac diseases, pre-initiation of oncological treatments, pre-participation in sports) and monitoring before induction of anaesthesia/sedation for non-cardiac procedures. Patients with incidentally found NSVT require further evaluation. A recent syncope suspicious for cardiac origin is a high-risk symptom and may prompt admission to hospital. The morphology of NSVT (polymorphic or monomorphic) is important to assess. Typical MVT morphologies (Figure 3) can suggest an idiopathic origin with favourable prognosis. In contrast, short-coupled PVC initiating non-sustained PVT or monomorphic NSVT with short cycle length

(usually,300 ms, average 245 + 28, in one series) may identify patients at higher risk of SCD. Resting 12-lead ECG is a first-line evaluation and may show signs of SHD or primary electrical diseases ( ESC CardioMed chapter 8.6). Echocardiography is the firstline imaging modality that provides important information about cardiac function and potential SHD ( ESC CardioMed 10.3, 10.10, 10.12). Holter monitoring is useful to assess the frequency of NSVT and related PVCs ( ESC CardioMed chapter 8.9). In addition, an at least 3-lead Holter (V1, two inferior leads) may give a first estimate if NSVT/PVC are unifocal or multifocal and of the NSVT site(s) of origin. The latter is important if the NSVT has not been previously documented on a 12-lead ECG.

An exercise test can be helpful to capture the 12-lead ECG of NSVT and to identify exercise-induced arrhythmias. Increasing arrhythmias with exercise, not suggestive of idiopathic origin, should raise suspicion of SHD and may necessitate advice to refrain from physical exercise until diagnosis and initiation of appropriate treatment. Underlying significant CAD should be ruled out according to the patient’s pre-test probability.

CMR should be considered when cardiomyopathies or inflammatory diseases are suspected on initial evaluation ( ESC CardioMed chapter 10.4). In addition, CMR can identify areas of fibrosis as substrates of NSVT.

Recommendation Table 3 — Recommendations for evaluation of patients presenting with newly documented ventricular arrhythmia

Recommendations	Classa	Levelb	© ESC 2022
In patients with newly documented VA (frequent PVCs, NSVT, SMVT), a baseline 12-lead ECG, recording of the VA on 12-lead ECG, whenever possible, and an echocardiogram are recommended asfrst-line evaluation.	I	C
In patients with newly documented VA (frequent PVCs, NSVT, SMVT) and suspicion of SHD other than CAD after initial evaluation, a CMR should be considered.194,195	IIa	B
In patients with an incidentalfnding of a NSVT, a≥24 h Holter ECG should be considered.	IIa	C

CAD, coronary artery disease; CMR, cardiac magnetic resonance; ECG, electrocardiogram; NSVT, non-sustained ventricular tachycardia, PVCs, premature ventricular contractions; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence.

5.2.2. Scenario 2: First presentation of sustained monomorphic ventricular tachycardia

An algorithm for the evaluation of patients presenting with a first SMVT episode is presented in Figure 4.

The majority of patients presenting with SMVT have underlying SHD. SMVT in SHD is mainly due to scar-related re-entry and only occasionally due to re-entry involving a diseased conduction system or due to focal sources.

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----- Start of picture text ----- Patient with incidental finding of NSVT (Cycle lengtheNSVT xercise induced)(Class I)evaluation, morpholog y, (CsymardptPioomsevascumrsoed, coniaclal a - r hitimorositnsk facor)briydititoesrs,, diseas (SCDFamie, prima, calry histodiory electricalmyropaty hy) (N T -)p(ElectLaboratoroBNro P l,ytes,TSH/T4)ry Ambulatory N Arrhythmic syncope or fast monomorphic NSVT Y Consider evaluation or short coupled PVC f ollowed by polymorphic NSVT admission 12-lead ECG Echocardiogram ≥24 h Holter (Class I) (Class I) (Class IIa) idiopathic originSuggestive of a Suggestive of SHDb primaSuggestiry electrical diseaseve/Diagnostic of c NSVT/PVC burden >10% Exclude CADd CMR N Y (Class IIa) Dischargee Idiopathic PVC/VT Go to section Furttohemrosevat lilu ka etily don accoiagnosridsing Prima Go to section ry electrical disease ----- End of picture text -----

Figure 2 Algorithm for the evaluation of patients presenting with an incidental finding of non-sustained ventricular tachycardia. CAD, coronary artery disease; CMR, cardiac magnetic resonance; ECG, electrocardiogram; N, No; NSVT, non-sustained ventricular tachycardia; PVC, premature ventricular complex; SCD, sudden cardiac death; SHD, structural heart disease; Y, Yes.[a] ECG morphology suggestive of RVOT or fascicular origin, negative family history, normal 12-lead ECG, and echocardiogram.[b] e.g. atrioventricular conduction abnormalities, Q waves, broad QRS complex, ST/T waves deviations, abnormally high or low voltages. Ventricular dysfunction/dilatation/hypertrophy/wall thinning, wall motion abnormalities, multitopic PVCs/NSVTs/increasing ventricular arrhythmia (VA) burden with exercise.[c] e.g. Brugada pattern, long/short QT, polymorphic/bidirectional VA with exercise.[d] Diagnostic test to exclude CAD according to patient profile and symptoms.[e] Consider re-evaluation in case of new symptoms or changes in patient clinical condition.

The diagnosis of the underlying aetiology and identification of patients with idiopathic VT is important. Initial evaluation includes a comprehensive clinical and family history, 12-lead ECG, and echocardiography. Recording of the 12-lead VT ECG is indicated as it provides important information on the VT site of origin. Specific VT morphologies (e.g. right ventricular outflow tract [RVOT] or fascicular origin) (Figure 3) in the absence of a family history for cardiomyopathies and without evidence for SHD are suggestive for idiopathic VTs. Atypical ECG morphologies and uncommon clinical presentations should raise suspicions for underlying SHD even if baseline ECG and echocardiogram are normal. In this scenario, additional evaluation with CMR should be considered. Bundle branch reentrant ventricular tachycardia (BBR-VT), resembling bundle branch block configuration on the ECG, is a feature of

conduction impairment, e.g. in DCM, myotonic dystrophy, and post-cardiac valve surgery (Figure 5).

If initial evaluation raises suspicion of underlying CAD, a CAG can exclude significant CAD. If ECG and echocardiography are suggestive for a cardiomyopathy, CMR provides important diagnostic information on scar distribution and tissue characteristics (Section 5.1.3.4). When non-invasive evaluation is inconclusive, electroanatomical mapping and PES may be considered for the differential diagnosis between idiopathic VT and early ARVC. Electroanatomical mappingguided biopsy can be of value to provide a tissue diagnosis for ARVC and inflammatory diseases with a focal distribution (e.g. cardiac sarcoidosis). In cases of suspected inflammatory diseases, positron emission tomography CT (PET-CT), autoimmune serology, and biopsies of affected tissue are part of the diagnostic evaluation.

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----- Start of picture text ----- RVOT VT (LBBB-like, inferior axis, V4 transition) ----- End of picture text -----

----- Start of picture text ----- LV fascicular VT (RBBB- like, superior axis, QRS 130 ms) ----- End of picture text -----

Figure 3 Typical idiopathic ventricular tachycardia morphologies. LBBB, left bundle branch block; LV, left ventricle; RBBB, right bundle branch block; RVOT, right ventricular outflow tract; VT, ventricular tachycardia.

Recommendation Table 4 — Recommendations for evaluation of patients presenting with a first episode of sustained monomorphic ventricular tachycardia

Recommendations	Classa	Levelb C © ESC 2022
In patients presenting with afrst SMVT episode, electrophysiological study, electroanatomical mapping, and mapping-guided biopsies may be considered for aetiological evaluation.197–199,202	IIb

SMVT, sustained monomorphic ventricular tachycardia. aClass of recommendation. bLevel of evidence.

5.2.3. Scenario 3: Sudden cardiac arrest survivor

An algorithm for the evaluation of sudden cardiac arrest survivors is presented in Figure 6.

Urgent CAG is recommended for patients presenting with ST elevation myocardial infarction (STEMI). Despite disparate findings of pooled data analyses, three randomized controlled trials (RCTs) have found no significant benefit for early CAG in cardiac arrest (CA) without ST-elevation. In case of electrical instability after CA, suspicious for ongoing ischaemia, this panel found a CAG indicated. Brain and chest CT scan may acutely identify non-cardiac causes of aborted SD, as well as blood test results for pertinent toxicological analysis. Retention and storage of suitable blood samples will allow subsequent diagnostic evaluation, including DNA analysis.

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----- Start of picture text ----- Patient with first SMVT episode (Cycle lengtheVT 12-lead ECGxercise induced)(Class I), morpholog y, (CsyamrdpPitooervascmemsonasd, coulical a h-mrtiirionsortsk faco)birydititoesrs,, diseas (SCDFamie, prima, calry histodiory electricalmyropaty hy) (N T -)p(ElectLaboratoroBNro P l,ytes,TSH/T4)ry 12-lead ECG Echocardiogram (Class I) (Class I) Suggestive of idiopathic origina Suggestive of CADb Suggestive of SHD other than CADc Go to section Idiopathic PVC/VT CAG No CAD Exclude CAD CADd CMR Go to section C AD (Class IIa) Suggestive of A R VCe Suggestive of other cardiomyopathyf Suggestive of inflammatory diseaseg N Y PE T -CT Cardiac/tissue biopsy Autoimmune serology Mapping-guided biopsy (if regional ventricular involvement) (Class IIb) negative positive EP study and R V electro-anatomical mapping Further evaluation Go to section Go to section (± mapping-guided biopsy) ARVC according to most li k ely Inflammatory (Class IIb) diagnosis ca r diac diseases ----- End of picture text -----

Figure 4 Algorithm for the evaluation of patients presenting with a first sustained monomorphic ventricular tachycardia episode. ARVC, arrhythmogenic RV cardiomyopathy; CAD, coronary artery disease; CAG, coronary angiography; CMR, cardiac magnetic resonance; ECG, electrocardiogram; EP, electrophysiological; LV, left ventricular; N, No; PET-CT, positron emission tomography and computed tomography; PVC, premature ventricular complex; RV, right ventricular; SCD, sudden cardiac death; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; VT, ventricular tachycardia; Y, Yes.[a] ECG morphology suggestive of RV outflow tract or fascicular origin, negative family history, normal 12-lead ECG, and echocardiogram.[b] e.g. Q waves, QRS fragmentation, ST/T abnormalities, wall motion abnormalities in coronary territories.[c] e.g. atrioventricular (AV) conduction abnormalities, Q waves, broad QRS complex, T-wave inversion, abnormally high or low voltages. Ventricular dysfunction/dilatation/hypertrophy/wall thinning/wall motion abnormalities/diffuse hypokinesia.[d] Diagnostic test to exclude CAD according to patient profile and symptoms. eAccording to revised task force criteria.116 fe.g. AV conduction abnormalities, abnormally high or low voltages, broad QRS, ST/T wave deviations, LV dilatation and dysfunction, late gadolinium enhancement with non-ischaemic distribution.[g] e.g. AV conduction abnormalities, broad QRS, ST/T deviations, multifocal PVCs, inflammatory hyperaemia and oedema, fibrosis, LV and RV systolic dysfunction, pericardial effusion.

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----- Start of picture text ----- ECG during sinus rhythm ECG during BBR-VT I I II II III III aVR aVR aVL aVL aVF aVF V1 V1 V2 V2 V3 V3 V4 V4 V5 V5 V6 V6 ----- End of picture text -----

Figure 5 Bundle branch re-entrant ventricular tachycardia. BBR-VT, bundle branch re-entrant ventricular tachycardia; ECG, electrocardiogram.

Any ECG tracing from emergency services, as well as recordings from interrogation of cardiovascular implantable electronic devices (CIEDs) can also contribute to diagnosis. The resting 12-lead ECG (including high precordial lead) is fundamental and should be repeated regularly during recovery. Continuous heart rhythm monitoring is recommended until definite treatment. Echocardiography may allow early diagnosis to identify any structural abnormality. Coronary imaging will be important to exclude CAD, dissection, or anomalies. Coronary optical coherence tomography and/or intravascular ultrasound may be helpful to characterize stenosis/plaque stability and underlying mechanism of stenosis. CMR has repeatedly been shown to provide significant incremental diagnostic value, in particular for concealed cardiomyopathy. Primary electrical diseases may be uncovered by provocative manoeuvres such as sodium channel blocker challenge, lying to standing ECGs, adenosine challenge, epinephrine challenge, ergonovine/ acetylcholine, mental stress, and exercise testing. Electrophysiological study and electroanatomic mapping may be useful to provide patient-specific insights

into the mechanism of CA and to offer therapeutic options in some patients. Genetic testing may identify a molecular cause of SCA by identifying pathogenic mutations in genes associated with specific phenotypes.

Recommendation Table 5 — Recommendations for evaluation of sudden cardiac arrest survivors

Recommendations	Classa	Levelb
Diagnostic evaluation
The investigation of a SCA survivor without obvious extra-cardiac cause is recommended to be overseen by a multidisciplinary team.177,251–256	I	B
In electrically unstable patients after SCA, with suspicion of ongoing myocardial ischaemia, a coronaryangiogram is indicated.	I	C

Continued

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In SCA survivors, brain/chest CT scan should be considered when patient characteristics, ECG, and echocardiography are not consistent with a cardiac cause.212,257	IIa	C	© ESC 2022
In SCA survivors, collection of blood samples at presentation is recommended for potential toxicology and genetic testing.56,214	I	B
Retrieval of recordings from CIEDs and wearable monitors is recommended for all SCA survivors.217,218	I	B
In SCA survivors, repeated 12-lead ECGs during stable rhythm (including high precordial lead ECG), as well as continuous cardiac monitoring, are recommended.220,222	I	B
Echocardiography is recommended for evaluation of cardiac structure and function in all SCA survivors.	I	C
Coronary imaging and CMR with LGE are recommended for evaluation of cardiac structure and function in all SCA survivors without a clear underlying cause.62,222,223,226	I	B
Sodium channel blocker test and exercise testing is recommended in SCA survivors without a clear underlying cause.117,222,258–260	I	B
In SCA survivors, ergonovine, acetylcholine, or hyperventilation testing may be considered for the diagnosis of coronary vasospasm.240,261	IIb	B

CIEDs, cardiac insertable electronic devices; CMR, cardiac magnetic resonance; CT, computed tomography; ECG, electrocardiogram; LGE, late gadolinium enhancement; SCA, sudden cardiac arrest. aClass of recommendation. bLevel of evidence.

5.2.4. Scenario 4: Sudden death victim

An algorithm for the evaluation of SD victims is presented in Figure 7.

Potential genetic cardiac disease can be identified in 25–49% of cases of SCD in the young (,50 years of age). This may also affect relatives of the deceased. To find the cause of death, it is important to collect all available data on prior symptoms, comorbidities, and family history.

The main role of autopsy in SD is to establish the cause of death. An expert cardiac pathologist alters the initial diagnosis in 41% of cases, highlighting the need for expert evaluation. Inherited cardiac diseases identified at autopsy include cardiomyopathies (HCM, DCM, ARVC) and premature CAD. A toxicology screen can reveal drug overdose or polypharmacy in 31–56% of young SD cases. In autopsy-negative cases with negative toxicology, the term sudden arrhythmic death syndrome (SADS) may be applied and primary electrical diseases are potential causes. Retaining tissue for DNA extraction is important for post-mortem genetic analysis, where the yield can be as high as one out of three.

Clinical evaluation of first-degree relatives is important if the cause of death after autopsy is unknown (Section 5.2.5, scenario 5) or

suspected to be inherited, with a reported combined diagnostic yield of genetic and clinical evaluation of 18–53%. Post-mortem genetic testing on the deceased, targeted to the cause of death, identified mutations in around one-third of cases.

Recommendation Table 6 — Recommendations for evaluation of sudden death victims

Recommendations	Classa	Levelb	© ESC 2022
Investigation of unexpected SD, especially in case of suspicion of inherited disease, should be made a public health priority.20,25,56	I	B
In cases of SD, it is recommended to collect a detailed description of circumstances of death, symptoms prior to death, the family history, and to review prior medicalfles.25,56	I	B
A comprehensive autopsy is recommended, ideally, in all cases of unexpected SD, and always in those,50 years of age.183,264,265,267,269,270	I	B
In cases of SCD, it is recommended to retain samples suitable for DNA extraction and consult a cardiac pathologist when an inherited cause is suspected or the cause of death unexplained.264,265	I	B
Toxicology screens are recommended in SD cases with uncertain cause of death.267,268	I	B
For SCD where the cause is known or suspected to be heritable, genetic testing targeted to the cause is recommended.56,266,269	I	B
Following SADS, post-mortem genetic testing targeted to primary electrical disease is recommended when the decedent is young (,50) and/or the circumstances and/or family history support a primary electrical disease.56,183,223	I	B
When an autopsy diagnoses possible heritable cardiac disease, it is recommended to refer frst-degree relatives for cardiac assessment in a specialized clinic.271,272	I	B
In non-autopsied cases of SD where inherited cardiac disease is suspected, it is recommended to referfrst-degree relatives for cardiac assessment in a specialized clinic.223,253,273	I	B
Following SADS, post-mortem genetic testing in the decedent for additional genes may be considered.	IIb	C
Following SADS, hypothesis-free post-mortem genetic testing using exome or genome sequencing is not recommended.274,275	III	B

DNA, deoxyribonucleic acid; SADS, sudden arrhythmic death syndrome; SCD, sudden cardiac death; SD, sudden death. aClass of recommendation. bLevel of evidence.

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5.2.5. Scenario 5: Relatives of sudden arrhythmic death syndrome decedents

An algorithm for the evaluation of relatives of SADS decedents is presented in Figure 8.

Studies evaluating families of SADS decedents have identified underlying genetic heart disease in relatives that is presumed to be the cause of death in the absence of other findings. The overall diagnostic yield ranged from 18 to 53%,

depending on population and clinical investigative protocols. Aetiologies included LQTS, BrS, CPVT, and other disorders, such as cardiomyopathy. All study protocols relied upon a similar initial approach of evaluating the decedent’s pathological reports, medical history, and circumstances of death, and then offering clinical evaluation to relatives with a minimum of personal history, family history, physical examination, ECG and exercise test, and echocardiography.

----- Start of picture text ----- SCA survivor 12-lead ECG (Class I) Urgent CAGa (Class I) Y STEMI N Electrical instability suspicious f or ongoing Y myocardial ischaemia N Evaluation of patient characteristics and circumstances of SCA Acute culprit lesion N (Class I) Y Echocardiogram (Class I) Further evaluation according to STEMI guidelines Suspicious f or extracardiac cause Y Brain and chest CT scan (Class IIa) N Extracardiac cause identified Y Non-cardiac N Collect blood sample f or toxicology and genetic testing (Class I) Review/Repeat ECG (Class I) Preexcited AF Prprimaeexcitation or suggestiry electrical diseaseve of Y or pelectrical diseaserobable primabr, cy N ----- End of picture text -----

Figure 6 Part One. Algorithm for the evaluation of sudden cardiac arrest survivors.

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----- Start of picture text ----- N Y Echocardiogram suggestive of CAD/ cardiomyopathy/valvular heart disease/other SHD N Cardiac CT/CAG (if previously not per f ormed) Further evaluation (Class I) according to most li k ely diagnosis. If SMV T, go to CAD/coronary anomaly Y CAD/Coronary anomaly scenario 2: P atient with f irst N SMVT episoded CMR (Class I) Y LGE on CMR N High lead and repeated 12-lead ECGs (Class I) Primary electrical disease Y Primary electrical disease N Sodium channel bloc k er test (Class I) Exercise test (Class I) Primary electrical disease Y N N Suspicion of vasospasme Y T est f or coronary vasospam (Class IIb) Positive Y V asospasm N Idiopathic VF ----- End of picture text -----

Figure 6 Part Two. Algorithm for the evaluation of sudden cardiac arrest survivors. AF, atrial fibrillation; CAD, coronary artery disease; CAG, coronary angiogram; CMR, cardiac magnetic resonance; CT, computed tomography; ECG, electrocardiogram; LGE, late gadolinium enhancement; N, No; SCA, sudden cardiac arrest; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; STEMI, ST elevation myocardial infarction; VF, ventricular fibrillation; Y, Yes.[a] The 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.[b] Rule out SHD according to patient age and characteristics; QT duration needs to be reassessed several days after arrest. cConsider cardiac CT/CAG depending on patient characteristics and clinical context. dLeft ventricular function on echocardiogram needs to be reassessed several days after arrest to exclude stunning as cause of systolic dysfunction.[e] In case of high clinical suspicion (typical symptoms and transient ST elevation during monitoring), it can be considered to test for coronary vasospasm earlier.

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----- Start of picture text ----- Sudden death victim Collect detailed description about: Circumstances of death Symptoms and prior history of deceased Family history (Class I) Comprehensive autopsya (Class I) S a ve blood f or potential toxicology testing (Class I) Non-cardiac cause of SD SCD of suspected inherited causeb SCD of non-inherited cause S a ve tissue f or potential genetic testing (Class I) Cause diagnosed Negative autopsy T argeted genetic testing T oxicology testing (Class I) (Class I) Re f or ca f er first-degrdiac assessmentree relatives Drug overdose Cause of death not dueto drug overdose (Class I) Sudden arrhythmic death syndrome (SADS) SADS decedent age <50 years or circumstances or family history suggestive of heritable disease Re f er first-degree relatives f or cardiac assessment (Class I) Post-mortem genetic testing with genetic counsellingc (Class I) Go to Scenario 5: Relatives of unexplained SD decedent ----- End of picture text -----

Figure 7 Algorithm for the evaluation of sudden death victims. SADS, sudden arrhythmic death syndrome; SCD, sudden cardiac death; SD, sudden death.[a] Autopsy is recommended, ideally in all cases of unexpected SD and always in those under 50 years. Autopsy should include full macroscopic examination and histopathology of all organs. The heart should ideally be examined by an expert cardiac pathologist. Samples suitable for DNA extraction should be retained when inherited causes or unexplained death are suspected.[b] Based on all circumstances, this includes negative autopsies, autopsies with uncertain findings, non-ischaemic cardiomyopathies, coronary artery disease where familial hypercholesterolaemia is suspected and thoracic aortic dissections.[c] After informed consent of relatives.

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Where they diverged was the frequency of usage of additional tests such as high-lead ECGs, Holter monitoring, signal-averaged ECG, CMR, and provocative testing. Sodium channel blocker drug challenge and high-lead ECGs systematically performed in SADS relatives provided a yield of 28% BrS diagnoses in one study; however, there are concerns about false positives. Furthermore, epinephrine challenge has not been studied systematically in SADS families but, in the opinion of this panel, may be of utility in CPVT-suspected patients who are unable to exercise.

Recent data indicated at least a 13% genetic yield in SADS cases. Routine follow-up of families without a diagnosis yields little in new diagnoses, although children of decedents may be followed for age-penetrant disease until adulthood.

If an autopsy is ambiguous, or if an autopsy was not undertaken in a young SCD case with family or personal history suspicious for inherited heart disease, then the yield of familial evaluation was similar to that in clear SADS cases.

Recommendation Table 7 — Recommendations for evaluation of relatives of sudden arrhythmic death syndrome decedents

Recommendations	Classa	Levelb
Familial evaluation of SADS decedents is recommended: • forfrst-degree relatives • for relatives who must carry a mutation based on analysis of the family history • for relatives with suspicious symptoms • when the decedent’s age is,50 years, or if there is other circumstantial data or family history to suggest heritable disease.223,252,253,277,281	I	B
Familial evaluation of SADS decedents is recommended to include genetic testing when post-mortem genetic testing in a SADS decedent detects a pathogenic mutation.183,253,277,281	I	B
Baseline familial evaluation of SADS decedents is recommended to include taking a medical history and performing physical examination, standard and high precordial lead ECG, echocardiography, and exercise testing.223,252,253,277,281	I	B
In SADS families without a diagnosis after clinical evaluation, follow-up is recommended for children of decedents until they reach adulthood.181,284	I	C
Pharmacological testing with a sodium channel blocker should be considered in relatives of SADS decedents who are 16 years or older when baseline testing and/or probandfndings increase the suspicion of BrS.277,281	IIa	B
		Continued

----- Start of picture text ----- Ambulatory cardiac rhythm monitoring and CMR may be considered in relatives of SADS IIb C decedents. Pharmacological testing including epinephrine challenge (if exercise testing is impractical) and sodium channel blocker challenge may be IIb B considered in first-degree relatives of SADS decedents with normal baseline testing. In SADS families without a diagnosis after clinical evaluation, follow-up is not recommended for asymptomatic adults who can be discharged with III C advice to return if they develop symptoms or if the family history changes. 2022 ESC © ----- End of picture text -----

BrS, Brugada syndrome; CMR, cardiac magnetic resonance; ECG, electrocardiogram; SADS, sudden arrhythmic death syndrome. aClass of recommendation. bLevel of evidence.

6. Therapies for ventricular arrhythmias. General aspects

6.1. Acute management

6.1.1. Treatment of reversible causes

Reversible causes may account for up to 50% of SCA. However, most of the time it is difficult to determine the exact underlying cause of SCA and whether it is reversible. A comprehensive evaluation of patients with SCA is mandatory if the underlying cardiac disease is unknown or disease progression is suspected (Section 5.2.3, scenario 3). Electrolyte imbalances, such as hypokalaemia, may trigger VA, and a rapid rise in extracellular potassium may lead to asystole. Other factors such as bradycardia, ischaemia, coronary spasm, thrombosis, fever, acute starvation, and dieting may contribute to the occurrence of VA. 290–292 Acute correction of these reversible factors is recommended.

Drug-induced arrhythmias should be suspected in patients being treated with agents known to alter the electrical properties of the heart (e.g. inducing QRS and/or QT prolongation) or causing electrolyte abnormalities (e.g. thiazide and loop diuretics). When drug-induced arrhythmias are presumed, any offending drug needs to be withdrawn and substances that are known to prolong QT (e.g. sotalol) should be avoided. Hypomagnesaemia and/or hypokalaemia may be associated with Torsades de pointes (TdP). Intravenous magnesium is an effective therapy for TdP even in the absence of hypomagnesaemia. In refractory cases of recurrent TdP in the setting of acquired long QT, the arrhythmia can be suppressed by increasing the underlying heart rate using isoproterenol (isoprenaline) or transvenous pacing.

Patients who survive SCA in the context of a presumed reversible cause may have a high mortality rate. In a recent large observational study on survivors of SCA attributed to a reversible and correctable cause, subsequent ICD implantation was associated with lower all-cause mortality except for aborted CA occurring in the presence of acute myocardial infarction (MI). Thus, the need for prophylactic ICD implantation should be considered based on the underlying cardiac disease and an individual evaluation of the future risk of life-threatening VA.

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----- Start of picture text ----- Relatives of unexplained sudden death decedent Non-autopsied SADS decedent SADS decedent sudden death decedent Genetic testing negative Pathogenic mutation identified with young age, family history of or not per f ormed SCD or circumstances (age <50 years or circumstances or suggestive of heritable heart disease family history suggestive of heritable disease) Familial evaluation in Familial evaluation in first-degree relatives, first-degree relatives, or relatives with suspicious obligate carriers or relatives symptoms with suspicious symptoms (Class I) according to condition (Class I) Medical history Genetic counselling and Physical examination cascade testing f or relatives Standard and high (Class I) precordial lead ECG Echocardiography Exercise testing (Class I) Diagnosis Y N Ambulatory cardiac rhythm monitoring and CMR (Class IIb) Clinical and/or Diagnosis Y genetic diagnosis N Sodium channel Manage relatives bloc k er testa according to condition (Class IIa) Epinephrine testb (Class IIb) Diagnosis Y N Follow-up f or children of decedent Discharge asymptomatic adultsc (Class I) ----- End of picture text -----

Figure 8 Algorithm for the evaluation of relatives of unexplained sudden death decedents. CMR, cardiac magnetic resonance; ECG, electrocardiogram; N, No; SADS, sudden arrhythmic death syndrome; SCD, sudden cardiac death; Y, Yes.[a] Over 16 years old + any suspicions for Brugada syndrome on tests or decedent circumstances of death.[b] If exercise is not feasible.[c] Re-evaluate if change in family history or new symptoms.

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Recommendation Table 8 — Recommendations for treatment of reversible conditions

----- Start of picture text ----- Recommendations Class [a] Level [b] Withdrawal of offending agents is recommended whenever drug-induced VAs are I B suspected. Investigation for reversible causes (e.g. electrolyte imbalances, ischaemia, hypoxaemia, fever) [c] is I C recommended in patients with VA. Despite a possible correctable cause for the presenting VA, the need for ICD implantation should be considered based on an individual IIa C evaluation of the risk of subsequent VA/ SCD. 2022 ESC © ----- End of picture text -----

ICD, implantable cardioverter defibrillator; SCD, sudden cardiac death; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence. cList not exhaustive.

6.1.2. Acute management of sustained monomorphic ventricular tachycardia

Patients presenting with SMVT should be treated according to symptoms and aetiology (Figure 9). Patients presenting with haemodynamic instability require immediate synchronized cardioversion. If synchronization is not possible, an unsynchronized shock should be used. Cardioversion is not indicated in patients with repetitive NSVTs (Figure 10). Documentation of any haemodynamically tolerated wide QRS tachycardia on 12-lead ECG is important. Administration of adenosine or vagal manoeuvres with continuous recording of 12-lead ECG should be considered if supraventricular tachycardia (SVT) is likely. Intravenous adenosine may also terminate specific VT subtypes. Such a response supports cyclic adenosine monophosphate (cAMP)-mediated triggered activity as an underlying VT mechanism. Pre-excited atrial fibrillation (AF) can be recognized by the ‘FBI’ (fast, broad, irregular) ECG pattern. It may mimic VT, and intravenous administration of drugs that slow AV conduction, such as adenosine, beta-blockers, and amiodarone, should be avoided. Prompt termination of SMVT is recommended even for tolerated SMVT, as rapid haemodynamical deterioration may occur.

----- Start of picture text ----- Acute management of a patient with regular wide QRS complex tachycardia Cardioversion/defibrillation/ALS N Haemodynamically Y History, physical examination, (Class I) tolerated 12-lead ECG Known or suspicion Adenosine or vagal of structural manoeuvres if SVT likely [a] heart disease (Class IIa) N Y IdiopathicVT Known Known Other type fascicularVT outflow tractVT or uncertain Anaesthetic risk Anaesthetic risk for cardioversion [b] for cardioversion [b] N Y N Y Verapamil Beta-blockers Procainamide Procainamide (Class I) (Class I) (Class IIa) (Class IIa) Flecainide Amiodarone Ajmaline (Class IIb) Sotalol Amiodarone [c] (Class IIb) Cardioversion (Class I) ----- End of picture text -----

Figure 9 Algorithm for the acute management of regular wide QRS complex tachycardia. ALS, advanced life support; ECG, electrocardiogram; N, No; SVT, supraventricular tachycardia; VT, ventricular tachycardia; Y, Yes.[a] Besides SVT, adenosine may also terminate idiopathic VT, which then indicates triggered activity as the mechanism underlying the arrhythmia.[b] Benefit of cardioversion should be weighed against risks related to anaesthesia/sedation. cConsidering limited availability of the other anti-arrhythmic drugs.

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Repetitive runs of VT mm:ss 00:00 00:30 01:00 01:30 02:00 02:30 03:00 03:30 04:00 04:30 05:00 05:30 06:00 06:30 07:00 07:30 08:00 08:30 09:00

Figure 10 Repetitive runs of ventricular tachycardia interrupted by occasional sinus beats. VT, ventricular tachycardia.

Termination can be achieved with electrical cardioversion, antiarrhythmic medications, or pacing techniques. All anti-arrhythmic drugs (AADs) may lead to hypotension, but the individual risk of anaesthesia/sedation required for cardioversion also needs to be considered. For pharmacological termination of a haemodynamically tolerated VT of unknown aetiology, intravenous procainamide or amiodarone can be used. In the PROCAMIO trial, procainamide therapy was associated with a higher proportion of tachycardia termination and fewer major cardiac adverse events than amiodarone. Intravenous procainamide should not be used in patients with severe heart failure, acute MI, and end-stage renal disease. Administration of other AADs (ajmaline, sotalol, and flecainide) may be considered in patients without significant heart disease, but the risk of adverse events should be carefully weighed. Availability of AADs has to be taken into account, e.g. procainamide is not available in many European countries. In patients with an ICD, manual

overdrive pacing may terminate those VTs with a cycle length under the programmed ICD detection rate. In case of a known idiopathic VT (Figure 4), treatment with beta-blockers (for RVOT VT) or verapamil (for fascicular VT) is recommended for acute conversion. Although verapamil may terminate other types of idiopathic VT, important adverse effects such as severe hypotension may occur. If the VT aetiology is uncertain, intravenous administration of verapamil is not recommended. A comprehensive evaluation of patients presenting with SMVT is mandatory if the underlying cardiac disease is unknown or disease progression is suspected (Section 5.2.2, scenario 2).

6.1.3. Management of electrical storm and incessant ventricular tachycardia

An electrical storm is common in ICD patients and has been defined as three or more episodes of sustained VA occurring within 24 h,

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requiring either anti-tachycardia pacing (ATP) or cardioversion/ defibrillation, with each event separated by at least 5 min. Patients who experience an electrical storm are prone to psychological disorders, heart failure decompensation, and increased mortality. The severity of an electrical storm can range from recurrent asymptomatic VT episodes terminated by ATP to a lifethreatening electrical instability with VA that recurs frequently after

multiple shocks. Frequent ICD shocks can also be inappropriately delivered (Figure 11).

In cases of inappropriate ICD shocks (e.g. due to SVTs or lead defects) or unnecessary ICD therapy (e.g. for NSVT or for repetitive VTs that terminate and restart spontaneously), disabling of ICD therapies is recommended. If an electrophysiology specialist or programmer is not available, the ICD can be disabled by placing a magnet over the device.

----- Start of picture text ----- Patient with electrical storm or repeated ICD discharges STEP 1 Rhythm assessment/ICD ICD Disable ICD by interrogation Inappropriate therapy due programming magnet placementif programmer of AF/SVTTreatment [a] to AF/SVT/lead oversensing optimization [a] not available (Class I) (Class I) (Class I) Inappropriate or unnecessary Y therapies ICD Disable ICD by N Recurrent non-sustained programming magnet placement if programmer VA episodes optimization [a] not available Electrical (Class I) (Class I) storm STEP 2 Assessment of ALS including external haemodynamic cardioversion/defibrillation status N (Class I) Haemodynamically Y Sedation (for comfort) stable (Class I) STEP 3 Assessment of VA type VA type PolymorphicVA MonomorphicVA ----- End of picture text -----

Figure 11 Part One. Management of patients with electrical storm or repeated implantable cardioverter defibrillator discharges.

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In case of haemodynamic instability at initial evaluation, institution of advanced life support (ALS) is recommended. Reversible conditions contributing to initiation and perpetuation of VA need to be corrected (see Section 6.1.1). Further management depends on the type of VA and the underlying aetiology. A multifaceted approach is often required for management, consisting of ICD reprogramming when appropriate, AAD therapy, sedation, catheter ablation, autonomic modulation, and mechanical circulatory support.

Elevated sympathetic tone needs to be addressed. For patients with recurrent ICD shocks, sedation is indicated to alleviate psychological distress and decrease pro-arrhythmogenic sympathetic tone. Initial treatment with beta-blockers, preferably non-selective betablockers like propranolol, which was superior to metoprolol in one study, combined with amiodarone is most commonly used. In patients with recurrent haemodynamically not-tolerated VTs resistant to amiodarone, landiolol (ultra-short-acting β1-selective blocker) was found to be effective for arrhythmia

suppression in two smaller studies. Administration of other AADs such as procainamide, lidocaine, or quinidine depends on the specific situation, type of VA, and underlying aetiology. When electrical storm remains intractable, with multiple shocks in a few hours, despite available anti-arrhythmic therapies, deep sedation/intubation should be considered, along with mechanical ventilation. If beta-blocker treatment is insufficient or not tolerated to decrease sympathetic tone, selected patients may benefit from autonomic modulation, i.e. percutaneous ganglionic stellate blockade, thoracic epidural anaesthesia, or left cardiac sympathetic denervation.

The most common arrhythmia underlying electrical storm is SMVT associated with SHD that is amenable to catheter ablation. Successful ablation was associated with a significant reduction in VT and electrical storm recurrence and improved long-term survival in retrospective analyses. In patients with incessant slow MVT, catheter ablation is preferred over AAD therapy,

----- Start of picture text ----- Polymorphic VA Underlying aetiology Acute External Polymorphic Acquired Primary ischaemia precipitating VA triggered long QT electrical factors by unifocal disease PVC Brugada, ERS Idiopathic VF Long QT, CPVT Go to Treatment Catheter Remove Isoproterenol Isoproterenol Beta-blocker fl owchart according to ablation precipitating (Class IIa) (Class IIa) (Class I) STEMI underlying (Class IIa) factors (Figure 14) condition(Class I) Quinidine [b] (Class I) Quinidine (Class IIa) Quinidine (Class IIa) (Class I)Pacing [d] (Class IIb) Mg [++] /K [+] i.v. Catheter Verapamil Mg [++] /K [+] i.v. (Class I) ablation (Class IIa) (Class I) Isoproterenol (Class IIa) Catheter AAD (Class I) ablation of according Pacing PVC triggers to underlying (Class I) (Class IIa) disease (Class IIa) Autonomic modulation (Class IIa) Recurrent VA Deep sedation/ intubation (Class IIa) Mechanical circulatory support (Class IIb) ----- End of picture text -----

Figure 11 Part Two.Management of patients with electrical storm or repeated implantable cardioverter defibrillator discharges.

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----- Start of picture text ----- MonomorphicVA VA burden [c] High Low ICD programming optimization [a] ICD programming optimization [a] (Class I) (Class I) Beta-blocker/sedation (Class I) On amiodarone or Amiodarone i.v. amiodarone not desirable N (Class I) AAD according to underlying disease and cardiac function Y Recurrent VA Recurrent VA Catheter ablation Catheter ablation (Class I) (Class I) Deep sedation/intubation (Class IIa) Autonomic modulation (Class IIb) Mechanical circulatory support (Class IIb) Overdrive pacing [e] ----- End of picture text -----

Figure 11 Part Three. Management of patients with electrical storm or repeated implantable cardioverter defibrillator discharges. AAD, antiarrhythmic drug; AF, atrial fibrillation, ALS, Advanced life support; CPVT, catecholaminergic polymorphic ventricular tachycardia; ERS, early repolarization syndrome; ICD, implantable cardioverter defibrillator; N, No; PVC, premature ventricular complex; STEMI, ST-elevation myocardial infarction; SVT, supraventricular tachycardia; VA, ventricular arrhythmia; VF, ventricular fibrillation; Y, Yes.[a] Special aspects of device therapy section.[b] No data on effect of quinidine on PVC-triggered polymorphic VAs in patients with cardiomyopathies.[c] High VA burden refers to a clinical scenario of very frequent VA episodes requiring ICD shocks, when only short periods of stable rhythm can be achieved. Low VA burden refers to a clinical scenario of repeated ATPs/ICD shocks followed by stable rhythm.[d] If bradycardia or post-extrasystolic pauses facilitate initiation of PVT/VF.[e] Overdrive pacing (by pacing with a slightly higher rate than the baseline rhythm) can be useful to temporarily suppress slow recurrent/incessant VT.

which may only further slow VT. Catheter ablation should also be considered in patients with recurrent symptomatic episodes of PVT or VF triggered by a similar PVC. Institution of mechanical circulatory support may be considered for haemodynamic stabilization, when conventional therapy fails, and to provide circulatory support during ablation. In a recent meta-analysis including 2465 patients, a substantially lower mortality was observed with prophylactic mechanical circulatory support treatment among patients suffering from electrical storm or high-risk PAINESD score. In contrast, rescue use of mechanical circulatory support during ablation was associated with a high mortality rate. In patients with electrical storm due to recurrent PVT/VF, the underlying aetiology determines further management (Figure 11).

Recommendation Table 9 — Recommendations for the acute management of sustained ventricular tachycardia and electrical storm

Recommendations	Classa	Levelb
Acute management of sustained VT
DC cardioversion is recommended as the frst-line treatment for patients with haemodynamically not-tolerated SMVT.303,339	I	B
DC cardioversion is recommended as the frst-line treatment for patients presenting with tolerated SMVT provided that the anaesthetic/ sedation risk is low.	I	C

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In patients presenting with a haemodynamically tolerated idiopathic VT, treatment with intravenous beta-blocker (RVOT VT) or verapamil (fascicular VT) is recommended.306,307	I	C
In patients presenting with a regular haemodynamically tolerated wide QRS complex tachycardia suspected for SVT, administration of adenosine or vagal manoeuvres should be considered.300	IIa	C
In patients presenting with a haemodynamically tolerated SMVT and known or suspected SHD, intravenous procainamide should be considered.303	IIa	B
In patients presenting with a haemodynamically tolerated SMVT in the absence of an established diagnosis, intravenous amiodarone may be considered.303	IIb	B
In patients presenting with a haemodynamically tolerated SMVT in the absence of signifcant SHD, fecainide, ajmaline, or sotalol may be considered.304,305	IIb	C
Intravenous verapamil is not recommended in broad QRS complex tachycardia of unknown mechanism.308,309	III	B
Management of electrical storm
Mild to moderate sedation is recommended in patients with electrical storm to alleviate psychological distress and reduce sympathetic tone.	I	C
Antiarrhythmic therapy with beta-blockers (non-selective preferred) in combination with intravenous amiodarone is recommended in patients with SHD and electrical storm unless contraindicated.317,318	I	B
Intravenous magnesium with supplementation of potassium is recommended in patients with TdP.295	I	C
Isoproterenol or transvenous pacing to increase heart rate is recommended in patients with acquired LQT syndrome and recurrent TdP despite correction of precipitating conditions and magnesium.	I	C
Catheter ablation is recommended in patients presenting with incessant VT or electrical storm due to SMVT refractory to AADs.330,331	I	B
Deep sedation/intubation should be considered in patients with an intractable electrical storm refractory to drug treatment.325	IIa	C
Catheter ablation should be considered in patients with recurrent episodes of PVT/VF triggered by a similar PVC, non-responsive to medical treatment or coronary revascularization.221,332,333	IIa	C
Quinidine may be considered in patients with CAD and electrical storm due to recurrent PVT when other AAD therapyfails.323,324	IIb	C

Autonomic modulation may be considered in patients with electrical storm refractory to drug IIb C treatment and in whom catheter ablation is ineffective or not possible. Institution of mechanical circulatory support may be considered in the management of IIb C drug-refractory electrical storm and cardiogenic shock. AAD, anti-arrhythmic drug; CAD, coronary artery disease; DC, direct current; LQT, long QT; PVC, premature ventricular complex; PVT, polymorphic VT; RVOT, right ventricular outflow tract; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; SVT, supraventricular tachycardia; TdP, Torsades de pointes; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

6.2. Long-term management

6.2.1. Pharmacotherapy

Optimal medical treatment of the underlying cardiac disease, including the maximal tolerated doses of heart failure medication, is mandatory.

In patients with heart failure with reduced ejection fraction (HfrEF), the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure recommend angiotensinconverting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitors (ARNIs), mineralo– corticoid receptor antagonists (MRAs), beta-blockers, and sodium glucose co-transporter 2 (SGLT2) inhibitors to reduce mortality due to heart failure and SCD.

Recommendation Table 10 — Recommendations for treatment with heart failure medication

Recommendations	Classa Levelb
Optimal medical treatment including ACE-I/ARB/
ARNIs, MRAs, beta-blockers, and SGLT2 inhibitors is indicated in all heart failure patients with reduced EF.343–347	I A	© ESC 2022
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker;
ARNIs, angiotensin receptor neprilysin inhibitor; EF, ejection fraction; MRA,
mineralocorticoid receptor antagonists; SGLT2, sodium–glucose co-transporter 2.
aClass of recommendation.
bLevel of evidence.

AADs have an important role as adjunctive therapy in the management of VA, especially in symptomatic patients (Table 8). Until now, no AAD except for beta-blockers has demonstrated reduction in allcause mortality. Each drug has a significant potential for causing adverse events, including pro-arrhythmia. For example, numerous AADs, as well as a large number of drugs with other therapeutic indications, can prolong the QT interval (http://www.crediblemeds.org) and provoke TdP, have negative chronotropic effects, may deteriorate heart failure, and cause bradycardia. Several drugs increase the risk of VA in patients with BrS (http://www.brugadadrugs.org).

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Table 8 Anti-arrhythmic drugs (acute and chronic treatment)

Anti-arrhythmic drug	Effects on ECG	Indications (specifc indication)	Oral dose per day (i.v. dose)	Side effects	Contraindications, precautions, other considerations
Amiodarone	Decreases sinus node frequency, prolongs QT intervala	PVC, VT, VF	200–400 mg Loading dose: 600–1200 mg/ 24 h 8–10 days. (Loading dose: 5 mg/kg in 20 min–2 h, 2–3 times in 24 h, then 600–1200 mg/ 24 h 8–10 days)	Cardiac: Bradycardia, TdP (infrequent) Extracardiac: Photosensitivity, corneal deposits, hypothyroidism, hyperthyroidism, pulmonary toxicity, hepatotoxicity, polyneuropathy, skin discoloration	Precautions: Sinus node dysfunction, severe AV conduction disturbances, hyperthyroidism Other considerations: Can be used in patients with heart failure. Increases the risk of myopathy when used with statins
Adenosine	Transitory AV block	Regular wide complex tachycardia of unknown origin (outfow tract VT)	No oral use (6–18 mg bolus)	Chest pain,fushing, bronchoconstriction	Contraindications: Severe asthma, pre-excited AF Other considerations: Antagonist: theophylline
Ajmaline	Prolongs QRS duration and QT intervala	VT (unmasking BrS ECG)	No oral use (1 mg/kg over 5–10 min (maximum dose 100 mg) or 1 mg/kg at 10 mg/min)	Cardiac: VF (rare in suspected BrS), occasional TdP, negative inotrope Extracardiac: Cholestatic jaundice, headache, nausea, thrombocytopenia	Contraindications: BrS ECG type I, QT prolongation
Beta-blocker	Decreases sinus node frequency, prolongs PR interval, shortens QT interval	PVC, VT (LQTS, CPVT)	Various (various)	Cardiac: Bradycardia, AV block, hypotension, negative inotrope Extracardiac: Fatigue, bronchospasm, sexual disturbances, depression, cold extremities	Contraindications: Severe sinus node dysfunction, severe AV conduction disturbances, decompensated heart failure, coronary vasospasm, severe asthma, BrS
Landiolol (Ultra-short acting β1-selective blocker)	See beta-blocker	VT, electrical storm	No oral use 100 µg/kg bolus in 1 min, infusion 10–40 µg/kg/min (max 80 µg/kg/ min; max 24 h total dose 57.6 mg/kg/day)	See beta-blocker	Contraindications: See beta-blocker. Bradycardia, hypotension Other considerations: Limited experience with its use beyond 24 h
Nadolol (Non-selective β1β2 blocker)	See beta-blocker	PVC, VT (LQTS, CPVT)	40–120 mg	See beta-blocker	Contraindications: See beta-blocker Other considerations: Plasma half-life 20–24 h
Propranolol (Non-selectiveβ1β2 blocker)	See beta-blocker	PVC, VT (electrical storm, LQTS, CPVT)	80–320 mg (160 mg/24 h)	See beta-blocker	Contraindications: See beta-blocker
Disopyramide	Increases sinus node frequency and prolongs PR interval, QRS duration, and QT intervala	PVC, VT	250–750 mg	Cardiac: Negative inotrope, AV block, pro-arrhythmia (MVT, occasional TdP)	Contraindications: Severe sinus node dysfunction, severe AV conduction disturbances, severe intraventricular

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				Extracardiac: Anticholinergic effects	conduction disturbances, prior MI, signifcant SHD, hypotension Other considerations: Reduces LV outfow tract obstruction and symptoms in HCM
Flecainide	Prolongs PR interval, QRS duration, and QT intervala	PVC, VT (unmasking BrS ECGb)	200–400 mg (1–2 mg/kg over 10 min)	Cardiac: Pro-arrhythmia (MVT, occasional TdP), negative inotrope, sinus bradycardia, AV block, 1:1 AV conduction during futter Extracardiac: Central nervous system effects (e.g. drowsiness, diplopia, headache)	Contraindications: Prior MI, signifcant SHD, BrS, severe sinus node dysfunction, severe AV or intraventricular conduction disturbances, inherited LQTS (other than LQTS3), severe kidney disease (CrCl,35 mL/min/1.73 m2) Other considerations: Discontinue if QRS widening.25% or bundle branch block
Isoproterenol	Increases sinus node frequency, shortens QT interval	(Electrical storm in BrS, idiopathic VF, and ERS, TdP, beta-blocker overdose; acquired LQTS)	No oral use (0.5–10 µg/min)	Cardiac: Sinus tachycardia, vasodilation Extracardiac: Headache, sweating, tremor	Contraindications: ACS, LQTS Other considerations: Short plasma half time (2 min)
Lidocaine	No signifcant effects	(VT/VF associated with ACS)	No oral use (50–200 mg bolus, then 2–4 mg/min)	Cardiac: Sinoatrial arrest Extracardiac: Central nervous system effects (e.g. drowsiness, dizziness)	Precautions: Reduced dose with reduced liver bloodfow (e.g. shock, β-blockade, severe heart failure) Other considerations: More effective with high potassium level. Few haemodynamic side effects
Mexiletine	No signifcant effects	PVC, VT (LQT3)	600–1200 mg Loading dose: 400 mg initially followed by 600 mg in thefrst 24 h	Cardiac: Sinus bradycardia in sinus node dysfunction, hypotension Extracardiac: Central nervous system effects (e.g. tremor, dysarthria, dizziness), gastrointestinal complaints	Contraindications: Sinus node dysfunction, severe AV conduction disturbances, severe heart failure
Procainamide	Prolongs PR interval, QRS duration, and QT intervala	VT	(100 mg bolus, can be repeated after 5 min if no effect, max 500– 750 mg [max 50 mg/min]. Then, 2–6 mg/min)	Cardiac: Sinus bradycardia, hypotension, TdP Extracardiac: Rash, myalgia, vasculitis, systemic lupus, agranulocytosis	Contraindications: Severe sinus node dysfunction, severe AV conduction disturbances, severe intraventricular conduction disturbances, severe LV dysfunction hypotension, BrS
Propafenone	Prolongs PR interval, QRS duration, and QT intervala	PVC, VT	450–900 mg	Cardiac: Sinus bradycardia, AV block, negative inotrope, pro-arrhythmia (MVT, occasional TdP) Extracardiac: Gastrointestinal disturbances, headache, dry mouth	Contraindications: Prior MI, signifcant SHD, BrS, severe sinus node dysfunction, severe AV or intraventricular conduction disturbances, LQTS, signifcant renal or liver disease Other considerations: Discontinue if QRS widening.25% or bundle branch block

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Quinidine	Increases sinus node frequency and prolongs PR interval, QRS duration, and QT intervala	(VFc, BrS, SQTS)	600–1600 mg Loading dose: Start 200 mg every 3 h until effect, max. 3 g in frst 24 h	Cardiac: Hypotension, TdPd Extracardiac: Gastrointestinal disturbances, auditory and visual disturbances, confusion, leukopenia, haemolytic anaemia, thrombocytopenia, anaphylaxis	Contraindications: Severe sinus node dysfunction, severe AV or intraventricular conduction disturbances, previous MI, signifcant SHD, hypotension, LQTS	© ESC 2022
Ranolazine	Decreases sinus node frequency, prolongs QT intervala	VT (LQTS3)	750–2000 mg	Cardiac: Sinus bradycardia, hypotension Extracardiac: Dizziness, nausea, constipation, gastrointestinal disturbance, headache, rash	Contraindications: Severe sinus node dysfunction, severe heart failure, LQTS (other than LQTS3) Precautions: Concomitant treatments associated with QT interval prolongation
Sotalol	Decreases sinus node frequency, prolongs QT intervala	VT	160–640 mg (0.5–1.5 mg/kg in 10 min. If necessary, can be repeated after 6 h)	See beta-blockers, TdPd (.2% of patients, close monitoring of QT interval and CrCl)	Contraindications: Severe sinus node dysfunction, severe AV conduction disturbances, severe heart failure with reduced LVEF, signifcant LVH, CrCl,30 ml/min, coronary vasospasm, LQTS Precautions: Concomitant treatments associated with QT interval prolongation, hypokalaemia Other considerations: Potassium channel blocker effects require higher dose than beta-blocker effects
Verapamil	Prolongs PR interval	(LV fascicular tachycardia)	120–480 mg (5–10 mg in slow bolus. If necessary, can be repeated in 30 min)	Cardiac: Sinus bradycardia in sinus node dysfunction, AV block, negative inotrope, hypotension Extracardiac: Gastrointestinal disturbances, peripheral oedema,fushing	Contraindications: Heart failure with reduced LVEF, severe sinus node dysfunction, and severe AV conduction disturbances, VT of unknown origin, ACS, WPW syndrome Other considerations: Increase the risk of myopathy when used with statins

ACS, acute coronary syndrome; AF, atrial fibrillation; AV, atrioventricular; BrS, Brugada syndrome; CPVT, catecholaminergic polymorphic ventricular tachycardia; CrCl, creatinine clearance; ECG, electrocardiogram; ERS, early repolarization syndrome; HCM, hypertrophic cardiomyopathy; LQTS, long QT syndrome; LV, left ventricular; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; MI, myocardial infarction; MVT, monomorphic ventricular tachycardia; PVC, premature ventricular complex; SHD, structural heart disease; SQTS, short QT syndrome; TdP, torsades de pointes; VF, ventricular fibrillation; VT, ventricular tachycardia; WPW, Wolff–Parkinson–White. aPrecaution with concomitant conditions or drugs that prolong QT interval. Should be discontinued if QTc.500 ms. See Figure 13 Algorithm for evaluation before initiation and follow-up of patients requiring drugs associated with QT prolongation. bIf ajmaline not available. cSubacute MI, multifocal ectopic Purkinje-related premature contractions, ERS, idiopathic VF. dProarrhythmic side effects require strong indication in patients without ICD.

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----- Start of picture text ----- Patient requiring sodium channel blocking agents Contraindications: Assessment of patient risk profile before initiation Brugada syndrome [a] Prior MI (flecainide) [b] Severe LV dysfunction Severe valvular heart disease Known cardiac disease or Severe bradycardia, BBB, > first degree AV block ECG abnormalities Y or Precaution: Abnormal echocardiogram Any degree of LV dysfunction LV hypertrophy N Any significant valvular heart disease First degree AV block Initiate treatment [c] Prolonged QT interval (disopyramide, quinidine) Initiate treatment on individual decision (risk/benefit) [d] ECG 1–2 weeks after initiation or increase in dosage [e] ΔQRS > 25% [f] or Consider to change to dffierent drug Abnormal exercise test? Y Consider to reduce dose (new BBB, ΔQRS >25% Consider to measure drug serum level or QRS >130 ms) N Continue treatment Inform patient about warning symptoms (syncope) Periodic ECG for QRS width evaluation Control changes in renal and hepatic function Be aware of potential drug interactions ----- End of picture text -----

Figure 12 Algorithm for evaluation before initiation and follow-up of patients requiring sodium channel blocking agents. AV, atrioventricular; BBB, bundle branch block; ECG, electrocardiogram; LV, left ventricular; MI, myocardial infarction; N, No; Y, Yes.[a] http://www.brugadadrugs.org.[b] Flecainide, encainide. cCo-administration of drugs with AV nodal blocking effect in patients with atrial fibrillation or atrial flutter. dIn implantable cardioverter defibrillator carriers, a higher risk of drug-induced pro-arrhythmia might be accepted.[e] According to the 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation. fA ΔQRS.25% is not an absolute cut-off value but dependent on QRS width before drug initiation and individualized patient risk–benefit considerations.

Modification of risk factors, when possible, is important for prevention of pro-arrhythmia. In patients who require a potentially arrhythmiainducing drug, regular ECG and other tests according to the patient’s profile and AAD characteristics are recommended (Figures 12 and 13).

6.2.2. Device therapy

6.2.2.1. Implantable cardioverter defibrillator

ICD is an integral part of treating patients surviving a CA due to a VA or those deemed to be at high risk thereof. Drawbacks are the high up-front device costs, device-associated complications, and the relatively high number-to-treat needed to prevent one SCD in primary prevention.

A patient-level meta-analysis of the three early ICD trials comparing ICD to medical therapy for secondary prevention of SCD demonstrated a 28% mortality reduction (HR 0.72; 95% CI 0.6–0.87; P = 0.0006) almost entirely due to reduction of arrhythmic death (HR 0.5; 95% CI 0.37–0.67; P, 0.0001) in the ICD group.

Therefore, the use of an ICD for secondary prevention of SCD that occurred in the absence of reversible causes is widely accepted.

Several randomized controlled trials have established the role of the ICD for primary prevention of SCD in heart failure patients with an LVEF ≤35%. The reported mortality reduction has recently been supported by two large contemporary prospective registries enrolling more than 5000 patients. In the EU-CERT-ICD trial, primary prevention ICD implantation was associated with a 27% lower mortality with similar results in CAD and DCM. Results of the DANISH trial, however, indicate that the mortality benefit may be less clear in contemporary patients with non-ischaemic heart failure (see Section 7.1.3.1).

In the work-up for ICD therapy, it is of paramount importance to consider the patient’s life expectancy, quality of life, and comorbidities, and to reassess and discuss these issues with the patient at the time of generator change. There is evidence that patients with end-stage renal disease, with diabetes, and elderly patients benefit less or not at all from

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----- Start of picture text ----- Patient requiring a drug associated with QT prolongationa Assessment of patient risk profile be f ore initiation baseline QTc >500 msLong QT syndrome orb Y Contraindicated: Do not initiate treatment N Hypokalaemia/hypomagnesaemia/ Renal failure/liver failure/ L V hypertrophy/ Y Start drug if strong indication with close f ollow-up Heart failure/ Additional QT prolonging drug N Initiate treatment ECG at baseline, after 1 d a y and after1–2 weeks of initiation or increase in dosagec Consider to change to di ff erent drug QTc >500 ms Y If strong indication, consider to reduce dose Consider to assess drug serum level Continue treatment N In f orm patient about warning symptoms (syncope) Control changes in renal and hepatic function Be a ware of potential drug interactions ----- End of picture text -----

Figure 13 Algorithm for evaluation before initiation and follow-up of patients requiring drugs associated with QT prolongation. ECG, electrocardiogram; LV, left ventricular; N, No; Y, Yes.[a] http://www.crediblemeds.org.[b] If strong indication and no alternative treatment, consult a specialist.[c] According to the 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation.

a primary prevention ICD. Women have been underrepresented in all primary prevention trials and data suggest that they may benefit less. In general, the SCD risk needs to be weighed against the individual’s competing risk of a non-arrhythmic death.

In the context of patient-centred medicine, physicians and healthcare professionals should engage ICD candidates and recipients in a joint decision process. Communication of relevant information, ensuring a good understanding of the benefits, risks, and potential consequences of different options, to enable the patient to partake in decision-making is mandatory. This shared decision-making process should discuss the different scenarios including primary prevention ICD implantation, consideration of ICD generator replacement, and end-of-life care. Importantly, the perception of ‘good quality of life’ depends on numerous factors that are weighed differently by people with different cultural, religious, and socioeconomic backgrounds. Although clinical prediction scores, such as the MADIT-ICD benefit score, may provide helpful additional information, clinical decision-making should not only rely on such scores.

Complications of ICD therapy include inappropriate therapies, lead fractures, and device-related infections. A subcutaneous implantable cardioverter defibrillator (S-ICD) has been introduced to address problems related to transvenous leads. S-ICD has no intravascular lead and therefore cannot deliver ATP. In the PRAETORIAN trial, 849 patients with an ICD but no pacing indication were randomized to an S-ICD or a transvenous ICD. Over a mean follow-up of 49 months, non-inferiority was shown for the primary endpoint of device-related complications and inappropriate shocks. The rate of inappropriate shocks was 9.7% in the S-ICD group and 7.3% in the ICD group (HR 1.43; 95% CI 0.89–2.30) and the rate of device related complications was 5.9% in the S-ICD and 9.8% in the ICD group (HR 0.69; 95% CI 0.44–1.09). There was also no difference in the secondary endpoint of death and appropriate shocks, but the trial had not been powered to show noninferiority for this secondary endpoint. Of note, more than 80% of the included patients were in NYHA class I and II and the included patients were younger than in prior ICD trials.

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Recommendation Table 11 — Recommendations for implantable cardioverter defibrillator implantation (general aspects)

Recommendations	Classa	Levelb	© ESC 2022
Implantation of a cardioverter defbrillator is only recommended in patients who have an expectation of good quality survival.1 year.	I	C
It is not recommended to implant an ICD in patients with incessant VAs until the VA is controlled.	III	C

ICD, implantable cardioverter defibrillator; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence.

Recommendation Table 12 — Recommendations for secondary prevention of sudden cardiac death*

Recommendations	Classa	Levelb	© ESC 2022
ICD implantation is recommended in patients with documented VF or haemodynamically not-tolerated VT in the absence of reversible causes.349–352	I	A
In patients with VT/VF, an indication for ICD, and no contraindication for amiodarone, amiodarone may be considered when an ICD is not available, contraindicated for concurrent medical reasons, or declined by the patient.	IIb	C
In patients with SMVT or SPVT/VF triggered by a PVC with similar morphology and an indication for ICD, catheter ablation may be considered when an ICD is not available, contraindicated for concurrent medical reasons, or declined by the patient.	IIb	C

ICD, implantable cardioverter defibrillator; PVC, premature ventricular complex; SMVT, sustained monomorphic VT; SPVT, sustained polymorphic VT; VF, ventricular fibrillation; VT, ventricular tachycardia. *For primary prevention and specific aspects of secondary prevention, go to Section 7. aClass of recommendation. bLevel of evidence.

Recommendation Table 13 — Recommendations for subcutaneous implantable cardioverter defibrillator

Recommendations	Classa	Levelb	© ESC 2022
Subcutaneous defbrillator should be considered as an alternative to transvenous defbrillator in patients with an indication for an ICD when pacing therapy for bradycardia, cardiac resynchronization, or ATP is not needed.366	IIa	B

ATP, anti-tachycardia pacing; ICD, implantable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

6.2.2.2. Adding cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) does reduce mortality in heart failure, and careful evaluation of the potential benefit of CRT in patients with ICD indication before implantation is mandatory. The role of the addition of a defibrillator is less well established. The ongoing randomized controlled RESET-CRT trial aims to determine the impact of CRT-defibrillator on overall mortality and SCD in heart failure patients with a CRT indication.

Recommendation Table 14 — Recommendations for adding cardiac resynchronization therapy to implantable cardioverter defibrillator

Recommendations	Classa	Levelb	© ESC 2022
When an ICD is indicated, it is recommended to evaluate whether the patient could beneft from CRT-defbrillator.367	I	C

CRT, cardiac resynchronization therapy; ICD, implantable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

6.2.2.3. Wearable cardioverter defibrillator

The wearable cardioverter defibrillator (WCD) is an external defibrillator that has been shown to successfully detect and treat VT and VF. It is therefore suitable for patients who are at risk but temporarily not candidates for an ICD owing, for example, to extraction of an infected device and subsequent antibiotic treatment. An unsolved problem is the protection of patients in the early phase (40 days) after an MI. The VEST trial enrolled 2302 patients with acute MI and an LVEF ≤35% and randomized them early in a 2:1 fashion to receive a WCD or not under guideline-directed optimal medical treatment (OMT). After a follow-up of 90 days there was no difference in the primary endpoint of arrhythmic death (1.6 vs. 2.4%; RR 0.67; 95% CI 0.37–1.21; P = 0.18). Concern was raised regarding the – low median wear time of 18 h (IQR 3.8 22.7). The median wear time was higher (23.4 h, IQR 22.2–23.8) in a recent multicentre registry after structured patient education. However, based on the available data, the task force does not recommend routine use of the WCD in the early post-MI phase. Nevertheless, the use of the device may be considered in selected post-MI patients deemed to be at high risk for SCD.

Data on the benefit of the WCD for primary prevention of SCD in other clinical situations (e.g. acute myocarditis, primary prevention indication during pregnancy) are sparse and no recommendations can be currently made.

Recommendation Table 15 — Recommendations for wearable cardioverter defibrillator

Recommendations	Classa	Levelb
The WCD should be considered for adult patients with a secondary prevention ICD indication, who are temporarily not candidates for ICD implantation.	IIa	C

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The WCD may be considered in the early phase after MI in selected patients.371,372 IIb B © ESC 2022	The WCD may be considered in the early phase after MI in selected patients.371,372 IIb B © ESC 2022
The WCD may be considered in the early phase after MI in selected patients.371,372	IIb

ICD, implantable cardioverter defibrillator; WCD, wearable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

6.2.3. Special aspects of device therapy

6.2.3.1. Optimization of device programming

Optimization of ICD programming is essential to minimize the burden of ICD therapy and to improve patient outcome. Detailed recommendations are available in expert consensus papers. Bradycardia mode should be customized to prevent unnecessary RV pacing, thus reducing heart failure hospitalizations and all-cause mortality ( ESC CardioMed chapter 43.21). A tachycardia detection programming strategy incorporating prolonged settings and high rate thresholds (≥188 b.p.m. Advance III trial, ≥200 MADIT-RIT) reduces ICD therapies and all-cause mortality without increasing the risk of syncope. The evidence is stronger for primary prevention compared to secondary prevention indications ( ESC CardioMed chapter 43.21). Consistent use of SVT/VT discriminators even in rates up to 230 b.p.m. is recommended in ICD recipients without complete heart block to reduce inappropriate therapies. Proper atrial sensing is a prerequisite for activation of dual-chamber discriminators ( ESC CardioMed chapter 43.21). In general, a multi-zone detection programming is favoured to enable tailored use of detection and therapy settings at different tachycardia rates. A single-zone programming with a high cut-off rate may be considered in patients with a high likelihood of VF only (e.g. primary electrical diseases). In subcutaneous ICDs, a dual-zone configuration should be adopted. Standardized programming including a lower ‘conditional shock’ zone with activated discrimination algorithms and a higher ‘shock zone’ based on rate criteria only has been shown to reduce inappropriate shock rates without compromising patient safety. Systematic use of ATP before shock delivery, also for very fast ventricular tachyarrhythmias, has been shown to reduce shock therapy without increase in arrhythmic syncope. Burst ATP is preferred over ramp due to increased efficacy in first tachycardia termination. Incorporation of remote monitoring into follow-up practice of ICD recipients should be promoted to optimize surveillance of device integrity, to enable prompt detection and management of actionable events, and to prevent occurrence of inappropriate shocks ( ESC CardioMed chapter 43. 21). The proposed recommendations for optimal device programming are applicable to the majority of ICD recipients. Customization may be needed in individual patients.

Recommendation Table 16 — Recommendations for optimization of device programming

Recommendations	Classa	Levelb
Optimization of ICD programming is indicated to avoid inappropriate and unnecessary therapies and to reduce mortality.373–375	I	A
		Continued

In single- or dual-chamber ICD patients without bradycardia pacing indications, it is recommended to minimize ventricular pacing.378–380	I	A	© ESC 2022
Programming of prolonged detection settings is indicated (duration criteria of at least 6–12 s or 30 intervals).373,382,383	I	A
It is recommended to program the slowest tachycardia therapy zone limit≥188 b.p.m. in primary prevention ICD patients.382,383	I	A
In patients with SHD, programming of at least one ATP therapy is recommended in all tachyarrhythmias zones.375,384,391	I	A
It is recommended to program algorithms for SVT vs. VT discrimination for tachycardias with rates up to 230 b.p.m.383–385	I	B
It is recommended to activate lead failure alerts.397–399	I	B
Remote monitoring is recommended to reduce the incidence of inappropriate shocks.395	I	B
Programming of burst ATP asfrst attempt is recommended over ramp ATP.392	I	B
For S-ICDs, a dual detection zone confguration is recommended with activation of discrimination algorithm in the lower conditional shock zone.388–390	I	B
For routine ICD programming, activation of more than one tachycardia detection zone should be considered.383,386	IIa	B

ATP, anti-tachycardia pacing; ICD, implantable cardioverter defibrillator; SHD, structural heart disease; S-ICD, subcutaneous ICD; SVT, supraventricular tachycardia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

6.2.3.2. Concomitant treatment to avoid inappropriate implantable cardioverter defibrillator therapy

Apart from optimization of device programming, pharmacological and/or invasive management may prevent inappropriate ICD therapy. Beta-blockers (carvedilol superior to metoprolol in MADIT-CRT) should be titrated to the maximal tolerated dose in heart failure patients to reduce the risk of inappropriate therapy. In patients with inappropriate therapies due to recurrent SVT, catheter ablation should be first-line treatment, given its high success and low complication rate. In case of AF-related inappropriate therapies, unresponsive to optimized pharmacological rate control treatment, individualized treatment strategy (rate vs. rhythm) dependent on patient characteristics is suggested. In patients with early AF, adoption of a rhythm control strategy improved patient outcome in the EAST-AFNET 4 trial. In CRT-defibrillator patients, AV node ablation has been associated with reduced inappropriate ICD shocks and lower hospitalization rates compared to drug treatment ( ESC CardioMed chapter 41.14).

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Recommendation Table 17 — Recommendations for concomitant treatment to avoid inappropriate implantable cardioverter defibrillator therapy

Recommendations	Classa	Levelb	© ESC 2022
Catheter ablation is recommended for ICD patients with recurrent SVT resulting in inappropriate ICD therapies.401,402	I	C
Pharmacological treatment or catheter ablation is recommended in patients with AF-related inappropriate ICD therapies despite optimal ICD programming.401,405,407	I	C

AF, atrial fibrillation; ICD, implantable cardioverter defibrillator; SVT, supraventricular tachycardia. aClass of recommendation. bLevel of evidence.

6.2.3.3. Psychosocial impact of implantable cardioverter defibrillator treatment

Almost 20% of ICD recipients suffer from anxiety and depression that are associated with increased mortality. In ICD patients, psychological distress is mainly caused by the concern of potentially receiving ICD shocks rather than by having experienced an ICD shock. Thus, assessment of ICD concerns is recommended in all ICD patients before ICD shocks occur. Systematic screening of ICD patients for psychological distress is feasible with the use of specific questionnaires.

A significant proportion of ICD patients with clinically relevant symptoms of anxiety and depression remains undertreated. Communication with all ICD recipients is needed to clarify misconceptions about the device function, to discuss concerns about sexual functioning, driving restrictions, and to recommend an action plan in case of shock therapy. Referral to mental health professionals may be needed for specific interventions. Cognitive behavioural therapy intervention may also be provided by trained cardiac nurses to alleviate anxiety. Web-based interventions may also prove useful in improving psychosocial well-being in ICD patients with increased psychosocial distress.

Recommendation Table 18 — Recommendations for psychosocial management after implantable cardioverter defibrillator implantation

Recommendations	Classa	Levelb	© ESC 2022
Assessment of psychological status and treatment of distress is recommended in ICD patients.421–423	I	C
Communication between patient and physician/ healthcare professional is recommended to address ICD-related concerns and to discuss quality-of-life issues before ICD implantation and during disease progression.412,424	I	C

ICD, implantable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

6.2.3.4. Patients with left ventricular assist devices

VAs are common among left ventricular assist device (LVAD) carriers. VAs are usually well-tolerated, as LVADs maintain adequate cardiac output and prevent circulatory collapse. However, sustained untreated VAs may lead to circulatory collapse even in the presence of an LVAD, especially early after device implantation and in patients with higher pulmonary vascular resistance. VAs pre- and post-LVAD implantation are associated with an increased risk of cardiovascular and all-cause mortality, while ICD can significantly reduce sustained VA. These data support ICD implantation for secondary prevention in LVAD recipients with symptomatic VA.

Observational studies in patients with previous-generation, pulsatile LVADs reported a longer survival with ICD ( ESC CardioMed chapter 37.32).

Recent registries enrolling continuous-flow LVAD carriers have questioned ICD mortality reduction, but available data are inconsistent. An analysis of the INTERMACS registry, enrolling the largest continuous-flow LVAD cohort, showed that ICD presence was not associated with prolonged survival. The lack of documented survival benefit among continuous-flow LVAD carriers, in conjunction with the likelihood of VA tolerance and the associated risks of ICD placement in these patients (risk of infection, device interaction), favours an individualized approach.

Recommendation Table 19 — Recommendations for implantable cardioverter defibrillator implantation in left ventricular assist device recipients

Recommendations	Classa	Levelb	© ESC 2022
ICD implantation should be considered in LVAD recipients with symptomatic sustained VAs.425,431	IIa	B

ICD, implantable cardioverter defibrillator; LVAD, left ventricular assist devices; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence.

6.2.3.5. Complications of devices

Prevention of ICD complications is important to reduce associated morbidity, mortality, and financial burden. During implantation of devices, antibiotic prophylaxis, peri-procedural patient preparation, and appropriate surgical technique should be implemented to prevent device infections and formation of pocket haematoma. Cephalic or axillary vein access is preferred over the subclavian vein route to reduce the risk of pneumothorax and lead failure. Proper selection of ICD systems is important. Single-chamber ICDs are recommended in primary prevention patients without atrial or AV sequential pacing indications. This reduces peri-procedural complications and generator replacements as compared to dual-chamber ICDs. This approach does not increase the risk of inappropriate shocks if optimal device programming is used. Routine use of single-coil defibrillator leads is favoured due to reduced risk of complications during lead removal without associated differences in shock efficacy. Use of dual-coil leads can be considered in clinical settings where a higher defibrillator threshold is suspected, e.g. HCM, right-sided implantations.

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Recommendation Table 20 — Recommendations for prevention of implantable cardioverter defibrillator complications

Recommendations	Classa	Levelb	© ESC 2022
Single-chamber ICD is recommended over dual-chamber ICD in primary prevention patients without current or expected indication for atrial or AV sequential pacing due to a lower risk of device-related complications.447,448,450	I	A
The use of single-coil leads over dual-coil ICD leads should be considered due to lower complication rate during transvenous lead extraction.451	IIa	C

AV, atrioventricular; ICD, implantable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

6.2.3.6. End-of-life issues

Patients with active ICDs experience a considerable rate of shocks in the last phase of life. In terminally ill patients and at the end of life, healthcare professionals can facilitate a decision by the patient and the patient’s family by explaining in a sensitive and understandable manner the benefits and burdens of continued ICD therapy. Patients should be informed about the options of ICD deactivation. In general, deactivation of anti-bradycardia therapy is discouraged to avoid quality-of-life impairment, and in some countries deactivation in pacemaker-dependent patients may be prohibited by law. Deactivation should be discussed before device implantation and when there is significant deterioration of the patient’s health status. Despite an increasing trend to address and perform device deactivation after careful consideration, current rates are still low and improved patient care is needed.

Recommendation Table 21 — Recommendations for end-of-life issues in implantable cardioverter defibrillator carriers

Recommendations	Classa	Levelb	© ESC 2022
Informed discussion with patient and family about ICD deactivation options and shared decision-making is indicated prior to implantation and in case of signifcant health status deterioration.458	I	C

ICD, implantable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

6.2.4. Interventional therapy

6.2.4.1. Catheter ablation

6.2.4.1.1. Patients with structural heart disease. In patients with SHD, SMVTs are primarily due to a scar-related re-entrant mechanism.

Because of a higher risk of SCD, an ICD implantation is usually recommended in patients with sustained VAs associated with

SHD. However, ICDs do not prevent VA, and many of these patients will experience symptomatic VT/VF recurrences resulting in syncope or ICD shocks and may require additional treatment.

In patients with SHD, the choice of anti-arrhythmic agents is mostly limited to beta-blockers, sotalol, and amiodarone to help control VT/VF recurrences, and this treatment is frequently hampered by side effects.

Owing to advances made over the last three decades, catheter ablation has become increasingly important for the management of scar-related VTs. Since the early 1990s, catheter ablation of BBR-VT has been very successful and is considered as firstline therapy (Figure 5). Subsequently, catheter ablation has been shown to be very effective in controlling incessant VTs or electrical storms and in reducing subsequent VT burden. Many observational studies have shown a positive effect of VT ablation on clinical outcome in terms of VT recurrences. In patients with CAD, three randomized trials have reported that catheter ablation, compared to conventional treatment, decreases the likelihood of subsequent ICD shocks and prevents recurrent VT episodes.

The critical part of re-entrant VT circuits, referred to as the ‘protected VT isthmus’, is the primary target for ablation, but it is very challenging to unmask in haemodynamically not-tolerated VT. Due to the high likelihood of multiple re-entry circuits in a scar and difficulties in identifying critical isthmuses, the ablation strategy has gradually evolved over the years towards more extended ablation of the arrhythmogenic substrate. Special attention should be paid to cases of PVT/VF initiated by similar PVCs, where the triggering PVC (often related to the Purkinje network) should be targeted for ablation.

The electrophysiological characteristics of VT circuits depend on the underlying SHD. Thus, post-infarct VTs are mainly related to an endocardial VT circuit (amenable to endocardial ablation), while the location of re-entrant VT circuits is more variable in patients with cardiomyopathies. Here, intramural and/or epicardial involvement are more common. This significantly contributes to the difference in the clinical outcomes of VT ablation in relation to the underlying heart disease with a better outcome in CAD as compared to non-ischaemic aetiologies.

Effective ablation requires durable ablation lesions to arrhythmogenic tissue. In some cases, such as intramural VTs, difficulties remain in achieving this objective with current catheters, regardless of the approach (endocardial/epicardial). To improve the formation of myocardial lesions, new catheter-based techniques are being evaluated (e.g. bipolar/needle ablation, transcoronary alcohol ablation), as well as radiotherapy ablation or surgical ablation, which are currently bailout treatments.

When planning VT ablation, it is important to collect all available information about the arrhythmogenic substrate, especially to identify scars (using CMR or CT scan), and to help determine the exit site of VAs with the 12-lead ECG documentation of clinical VTs or PVCs that induce PVT/VF.

The mean long-term success rate of VT ablation varies from 30% to 70%, depending on the underlying SHD. Peri-procedural complications, in particular stroke, cardiac tamponade, or death, may occur.

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6.2.4.1.2. Patients without apparent structural heart disease.

‘Idiopathic VTs’ is the term for VTs that are not associated with SHD or a genetic arrhythmic syndrome. Most idiopathic VTs are mediated by triggered activity, but a re-entrant mechanism (involving the LV Purkinje network) explains verapamil-sensitive fascicular VTs. Three important key features distinguish idiopathic VTs from VTs associated with SHD. First, idiopathic VTs mostly originate from a single site and specific region of the heart (namely the right or left ventricular outflow tracts, along the valve annuli, papillary muscle, or the LV Purkinje network). Second, no detectable scar is found in idiopathic VTs. Finally, idiopathic VTs have a benign prognosis so that ICD implantation is generally not recommended.

The earliest site of activation during VT is the ablation target for focal sources, while abnormal Purkinje tissue (with diastolic activity during VT) is the ablation target of left fascicular VTs.

Catheter ablation is curative in most idiopathic VT patients and peri-procedural complications are rare.

6.2.4.2. Autonomic modulation

The role of the autonomic nervous system in promoting arrhythmias has long been recognized, leading to the concept of Coumel’s triangle of arrhythmogenesis.

Sympathetic activation has been demonstrated as playing a key role in inducing VAs in some entities, such as congenital LQTS and CPVT, and left cardiac sympathetic denervation was shown to be associated with a decrease in the frequency of arrhythmogenic syncope in congenital LQTS. The efficacy of cardiac sympathetic blockade by different approaches (thoracic epidural anaesthesia, percutaneous stellate ganglion anaesthesia, or surgical stellate ganglion resection) in reducing the arrhythmia burden in refractory VT/VF has been recognized in several small observational studies. Further studies are needed to assess which patients may benefit from a modulation of the autonomic nervous system to better control VT/VF.

7. Diagnostic evaluation, management, and risk stratification according to clinical presentation and known (likely) disease

7.1. Specific structural heart diseases

7.1.1. Coronary artery disease

7.1.1.1. Acute coronary syndromes and vasospasm

7.1.1.1.1. Acute coronary syndromes. SCD is a major cause of

mortality in ACS, mostly caused by sustained VAs, in particular VF. The majority of studies have reported on patients with STEMI. Of patients with STEMI, 4–12% develop VA within the first 48 h after the onset of symptoms. Pre-reperfusion VAs are more common than reperfusion-induced or postreperfusion arrhythmias in STEMI. Haemodynamic instability, cardiogenic shock, LVEF, 40%, and the sum of ST-segment deviations in all leads are independent predictors of VA both in

STEMI and non-STEMI. In addition, an early repolarization pattern has been associated with increased risk of VAs and SCD in ACS.

Prevention of ventricular arrhythmias in ST elevation myocardial infarction

Urgent reperfusion is the most important therapy, as acute ischaemia triggers arrhythmias. Beta-blocker treatment is also recommended to prevent VA. In a recent randomized trial of patients with STEMI, early intravenous metoprolol before percutaneous coronary intervention reduced the incidence of arrhythmias in the acute phase and was not associated with an increase in adverse events. Prophylactic treatment with AADs has not proven beneficial, and may even be harmful. Correction of electrolyte imbalances is strongly recommended.

Management of sustained ventricular tachycardia and ventricular fibrillation in acute coronary syndrome

Electrical cardioversion or defibrillation is the intervention of choice to acutely terminate VAs in ACS patients (Figure 14). Recurrent sustained VT, especially when polymorphic, or recurrent VF can indicate incomplete reperfusion or recurrence of acute ischaemia. In this case, immediate coronary angiography is indicated. For recurrent PVT degenerating into VF, beta-blockers are recommended. In addition, deep sedation may be helpful to reduce episodes of VT or VF. Intravenous amiodarone should be considered to acutely suppress recurrent haemodynamically relevant VAs, although there is a paucity of controlled studies for amiodarone during STEMI and the evidence in this setting is mainly extrapolated from studies of OHCA. If treatment with beta-blockers and amiodarone is not effective, lidocaine may be considered. The use of other AADs in ACS is not recommended. In haemodynamically unstable patients with refractory VA, mechanical circulatory support may be considered. For VA in the context of relative bradycardia or pause-related, pacing may be effective to prevent re-initiation.

The prognostic significance of early ventricular arrhythmias

Early VAs are defined as VT/VF occurring within 48 h after a STEMI. In the contemporary percutaneous coronary intervention (PCI)-based revascularization era, almost all VA occur within the first 24 h. Early VA have been associated with an up to six-fold increase in in-hospital mortality, whereas long-term prognosis seems not to be significantly affected. In a prospective cohort study, patients with VF during the acute STEMI phase had low and very similar incidence of late SCD as compared with VF-free patients during 5-year observation. Of note, early monomorphic VT was associated with significantly higher incidence of adequate ICD interventions compared with early VF, and was an independent predictor - of death during long-term follow-up. Thus, the prognostic signifi cance of VT and VF occurring in the acute phase of MI may be different. The impact of VA occurring late after reperfusion (.48 h) on late SCD is less clear.

Podolecki et al. recently demonstrated that long-term all-cause mortality after STEMI was predicted by VA occurring late after reperfusion (.48 h after reperfusion), while early reperfusion VAs did not affect 5-year outcome. Further studies are required to clarify

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----- Start of picture text ----- Prevention and treatment of VAs in the acute phase of STEMI Beta-blocker i.v. prior to PCI, if not contraindicated [a,b] (Class IIa) Urgent CAG and revascularization [a] (Class I) VA Further revascularization if appropriate [a] (Class I) Repletion of K [+], Mg [2+ a] (Class I) Beta-blocker i.v. [b] (Class I) Sedation (for comfort) [c] (Class I) Recurrent VA Amiodarone i.v. (Class IIa) Lidocaine i.v. (Class IIb) Deep sedation/intubation [c] (Class IIb) Recurrent VA Catheter ablation [d] (Class IIa) Overdrive pacing [a] (Class IIa) Autonomic modulation [c] (Class IIb) Mechanical circulatory support [c] (Class IIb) ----- End of picture text -----

Figure 14 Algorithm for the prevention and management of ventricular arrhythmias in ST-elevation myocardial infarction. CAG, coronary angiogram; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; VA, ventricular arrhythmias.[a] The 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.[ b] Intravenous beta-blockers must be avoided in patients with hypotension, acute heart failure, AV block or severe bradycardia.[c] Flowchart for the management of electrical storm.[d] If similar PVC triggers recurrent polymorphic VA.

the impact of VA occurring.48 h after STEMI on late SCD in contemporary patients undergoing acute PCI.

7.1.1.1.2. Vasospasm. Coronary artery spasms might have an important role in the pathogenesis of VA. The long-term prognosis

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Recommendation Table 22 — Recommendations for treatment of ventricular arrhythmias in acute coronary syndrome and vasospasm

Recommendations	Classa	Levelb
Treatment of VAs in ACS
Intravenous beta-blocker treatment is indicated for patients with recurrent PVT/VF during STEMI unless contraindicated.551,552	I	B
Intravenous amiodarone treatment should be considered for patients with recurrent PVT/VF during the acute phase of ACS.552,554,555	IIa	C
Intravenous lidocaine may be considered for the treatment of recurrent PVT/VF not responding to beta-blockers or amiodarone, or if amiodarone is contraindicated during the acute phase of ACS.554	IIb	C
Prophylactic treatment with AADs (other than beta-blockers) is not recommended in ACS.322	III	B
Vasospasm
In SCA survivors with coronary artery spasm, implantation of an ICD should be considered.562–564	IIa	C

AAD, anti-arrhythmic drug; ACS, acute coronary syndrome; ICD, implantable cardioverter defibrillator; PVT, polymorphic ventricular tachycardia; SCA, sudden cardiac arrest; STEMI, ST elevation myocardial infarction; VA, ventricular arrhythmia; VF, ventricular fibrillation. aClass of recommendation. bLevel of evidence.

of patients with variant angina who survive a CA is worse than in other patients with variant angina. In a recent multicentre European survey, patients with life-threatening VAs secondary to coronary vasospasm were at high risk for recurrence, especially when insufficient medical therapy was administered. While calcium channel blockers (CCB) are capable of suppressing episodes, betablockers may trigger VAs. As medical intervention and multiple vasodilator drugs may not be sufficiently protective, placement of an ICD should still be considered in SCA survivors with variant angina.

7.1.1.2. Early after myocardial infarction

The first weeks after a STEMI carry the highest risk both for allcause death and for SCD, particularly in patients with reduced LVEF. For this reason, early assessment of LVEF, i.e. before discharge, is recommended. Early routine prophylactic ICD implantation in the first 40 days after MI did not reduce mortality in post-MI patients with reduced LVEF in two randomized trials (DINAMIT and IRIS), and is therefore not recommended. Early assessment by further non-invasive tests, apart from LVEF measurement, has also not proven to be useful for risk stratification with regard to SCD. Limited evidence suggests that invasive risk stratification by PES in the early post-MI phase may be helpful for identification of high-risk patients with reduced LVEF. However, the utility of this approach has not been confirmed so

far in randomized studies. The PROTECT-ICD randomized trial (NCT03588286) is currently examining whether PES may guide the decision on ICD implantation in patients with reduced EF in the early phase after STEMI.

Reverse remodelling following an MI is associated with significantly lower rates of death, SCA, and other adverse clinical outcomes. Therefore, assessment of the indication for prophylactic ICD implantation, usually performed by repeat echocardiography, should take place in the post-remodelling phase of the MI after the first 6 weeks in patients with a pre-discharge LVEF ≤40%. Reassessment of the LVEF before 6 weeks following MI may not discriminate between myocardial stunning and remodelling.

In the early post-MI phase, electrical storm and/or recurrent episodes of PVT or VF are immediately life-threatening conditions. In this setting, it is important to exclude ischaemia as the triggering factor for the arrhythmias. If medical treatment is not sufficient to suppress the arrhythmic episodes, catheter ablation is potentially effective particularly if the episodes are focally triggered by similar PVCs. If PVT recurs despite betablocker and amiodarone treatment, suppression by quinidine therapy has been reported.

Recommendation Table 23 — Recommendations for risk stratification and treatment of ventricular arrhythmias early after myocardial infarction

Recommendations	Classa	Levelb
Risk stratifcation
Early (before discharge) assessment of LVEF is recommended in all patients with acute MI.567,568	I	B
In patients with pre-discharge LVEF≤40%, re-evaluation of LVEF 6–12 weeks after MI is recommended to assess the potential need for primary prevention ICD implantation.568,573,574	I	C
Treatment of VAs
Catheter ablation should be considered in patients with recurrent episodes of PVT/VF triggered by a similar PVC non-responsive to medical treatment or coronary revascularization in the subacute phase of MI.332	IIa	C

ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PVC, premature ventricular complex; PVT, polymorphic ventricular tachycardia; VA, ventricular arrhythmia; VF, ventricular fibrillation. aClass of recommendation. bLevel of evidence.

7.1.1.3. Chronic coronary artery disease

7.1.1.3.1. Primary prevention of sudden cardiac death in patients with reduced ejection fraction. Forty days after STEMI, approximately 5% of patients will have an LVEF ≤35%. These patients are at risk for SCD. Therefore, in patients with LVEF ≤35% and

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heart failure symptoms NYHA class II and III, primary preventive ICD implantation is recommended. ICD implantation should also be considered for asymptomatic patients with an EF ≤30%. In this population, mortality reduction by an ICD has been demonstrated in four RCTs. In patients with CAD, a reduced LVEF (≤40%), and asymptomatic NSVT, inducibility by PES identifies patients who benefit from an ICD, independent from NYHA class.

Since the publication of the aforementioned trials, early revascularization strategies and modern heart failure medication have reduced the overall risk of SCD in heart failure patients. Although total mortality has been reduced, the relative reduction by the ICD is a consistent 27%, which has been corroborated in two recent large prospective registry studies enrolling 2327 European patients between 2014 and 2018 (EU-CERT-ICD) and 2610 Swedish patients enrolled between 2000 and 2016 (SwedeHF registry).

Recommendation Table 24 — Recommendations for risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmias in chronic coronary artery disease

Recommendations	Classa	Levelb
Risk stratifcation and primary prevention of SCD
In patients with syncope and previous STEMI, PES is indicated when syncope remains unexplained after non-invasive evaluation.146,584	I	C
ICD therapy is recommended in patients with CAD, symptomatic heart failure (NYHA class II–III), and LVEF≤35% despite≥3 months of OMT.354,356	I	A
ICD therapy should be considered in patients with CAD, NYHA class I, and LVEF≤30% despite≥3 months of OMT.354	IIa	B
ICD implantation should be considered in patients with CAD, LVEF≤40% despite≥3 months of OMT, and NSVT, if they are inducible for SMVT by PES.355	IIa	B
In patients with CAD, prophylactic treatment with AADs other than beta-blockers is not recommended.556,578,579	III	A
Secondary prevention of SCD and treatment of VAs
ICD implantation is recommended in patients without ongoing ischaemia with documented VF or haemodynamically not-tolerated VT occurring later than 48 h after MI.349–351	I	A
In patients with CAD and recurrent, symptomatic SMVT, or ICD shocks for SMVT despite chronic amiodarone therapy, catheter ablation is recommended in preference to escalating AAD therapy.471	I	B
		Continued

The addition of oral amiodarone or beta-blocker replacement by sotalol should be considered in patients with CAD with recurrent, symptomatic SMVT, or ICD shocks for SMVT while on beta-blocker treatment.318,581	IIa	B	© ESC 2022
In patients with CAD and haemodynamically well-tolerated SMVT and LVEF≥40%, catheter ablationinexperiencedcentresshouldbeconsidered as an alternative to ICD therapy, provided that established endpoints have been reached.c,480,580	IIa	C
ICD implantation should be considered in patients with a haemodynamically tolerated SMVT and an LVEF≥40% if VT ablation fails, is not available, or is not desired.	IIa	C
Catheter ablation should be considered in patients with CAD and recurrent, symptomatic SMVT, or ICD shocks for SMVT despite beta-blockers or sotalol treatment.471	IIa	C
In patients with CAD eligible for ICD implantation, catheter ablation may be considered just before (or immediately after) ICD implantation to decrease subsequent VT burden and ICD shocks.484,485,582,583	IIb	B

AAD, anti-arrhythmic drug; CAD, coronary artery disease; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; OMT, optimal medical therapy; PES, programmed electrical stimulation; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycardia; STEMI, ST elevation myocardial infarction; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cVT non-inducibility and elimination of electrograms consistent with conduction delay.

7.1.1.3.2. Primary prevention of sudden cardiac death in patients with preserved or mildly reduced ejection fraction. There are no data supporting primary prophylactic ICD implantation in post-infarct patients with preserved or mildly reduced LVEF. These patients are heterogeneous with regard to their potential arrhythmic substrate, and efforts are under way to identify those with the highest risk for SCD. PES is recommended in post-infarct patients in whom syncope remains unexplained after non-invasive evaluation to guide patient management (Figure 15).

In the PRESERVE-EF study, 41 of 575 post-infarct patients with an LVEF ≥40% and one non-invasive ECG risk factor more than 40 days post-MI were inducible for VT/VF during PES and received an ICD. During the 32-month follow-up period, no SCD occurred and 9 of 37 ICD patients received an appropriate ICD therapy. However, the role of appropriate ICD treatment as surrogate for SCD in patients with preserved LVEF is unknown, and randomized trials are needed. Prophylactic treatment with AADs other than beta-blockers is not indicated regardless of the LVEF.

7.1.1.3.3. Secondary prevention of sudden cardiac death. The three pivotal secondary prevention ICD trials enrolled 1866 patients between 1990 and 1997. A patient-level

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----- Start of picture text ----- Patient with chronic CAD L VEF evaluation 6–12 weeks after acute MI in patients with L VEF ≤40% at discharge (Class I) L VEF 36–40% L VEF ≤35% NSVT or N NYHA class ≥II Y unexplained syncope ICD Follow-up Y N (Class I) PES N L VEF ≤30% Y (Class I) No SMVT inducible SMVT inducible and unexplained syncope ILR implantationa ICD implantation ICD implantation (Class I) (Class IIa) (Class IIa) ----- End of picture text -----

Figure 15 Algorithm for risk stratification and primary prevention of sudden cardiac death in patients with chronic coronary artery disease and reduced ejection fraction. CAD, coronary artery disease; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; LVEF, left ventricular ejection fraction; MI, myocardial infarction; N, No; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; PES, programmed electrical stimulation; SMVT, sustained monomorphic ventricular tachycardia; Y, Yes.[a] The 2018 ESC Guidelines for the diagnosis and management of syncope.

meta-analysis demonstrated a 28% mortality reduction (HR 0.72; 95% CI 0.60–0.87; P = 0.0006) almost entirely due to reduction of arrhythmic death (HR 0.50; 95% CI 0.37–0.67; P, 0.0001) in the ICD group. This translates to an extension of survival of 4.4 months over a mean follow-up of 6 years by the ICD. Around 80% of the study population suffered from CAD. Patients with well-tolerated SMVT were excluded from secondary prevention trials (Figure 16).

7.1.1.3.4. Management of patients with haemodynamically tolerated ventricular tachycardia and preserved and mildly reduced ejection fraction. With the better understanding of the mechanisms of VT after MI, as well as improved ablation and imaging technologies, catheter ablation has become an option for the treatment of haemodynamically well-tolerated VT in selected post-MI patients with preserved or mildly reduced EF, even without ICD back-up. One small monocentric retrospective trial studied patients with CAD, LVEF.40%, and haemodynamically tolerated VT who underwent catheter ablation as first-line therapy. The investigators could abolish

90% of the clinical and 58% of all inducible VTs. Subsequently, 42% of the patients received an ICD. After a mean follow-up of 3.8 years, 42% of the patients died irrespective of the presence or absence of an ICD (P = 0.47).

A larger multicentre retrospective study looked at 166 patients with an LVEF.30% presenting with well-tolerated SMVT, which were treated by catheter ablation only, and compared the outcome to a control group of 378 patients implanted with an ICD. Of the 166 patients undergoing ablation as first therapy, 55% suffered from CAD. The mean LVEF was 50%, and after a mean follow-up of 32 months, overall mortality did not differ between the groups (12%).

These data suggest that either ICD implantation or ablation in experienced centres should be considered in patients with a preserved or mildly reduced EF presenting with haemodynamically tolerated SMVT. Of note, although ICDs have been commonly implanted in this population, the secondary preventive ICD trials failed to show a survival benefit in patients with an LVEF ≥35%. Although SMVT is rarely caused by ischaemia and revascularization alone

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----- Start of picture text ----- SMVT in a patient with chronic CAD First presentation SMVT in ICD carriersa ≥40% L VEF <40% Electrical storm Symptomatic SMVT Go to flowchart Haemodynamically N electrical storm On amiodarone tolerated (Figure 11) Y Y N Catheter ablation ICD implantation Catheter ablation Catheter ablation (Class IIa) (Class I) (Class I) (Class IIa) ICD implantationb Catheter ablation Sotalolc (Class IIa) (Class IIb) (Class IIa) Amiodaroneb Amiodarone (Class IIa) (Class IIa) ----- End of picture text -----

Figure 16 Algorithm for the management of sustained monomorphic ventricular tachycardia in patients with chronic coronary artery disease. CAD, coronary artery disease; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; N, No; SMVT, sustained monomorphic ventricular tachycardia; Y, Yes.[a] Incessant ventricular tachycardia in monitor zone: consider catheter ablation.[b] If catheter ablation is not available, not successful or not desired by the patient.[c] To reduce ICD shocks.

does not prevent VT recurrence, exclusion or treatment of significant CAD before catheter ablation is reasonable.

However, in patients who present with a first VT episode and in whom an ICD is indicated, catheter ablation performed immediately before or shortly after ICD implantation may be considered to decrease subsequent VT and ICD shocks.

7.1.1.3.5. Management of recurrent ventricular tachycardia in implantable cardioverter defibrillator carriers. Frequent, symptomat-

ic VT in ICD recipients should be treated medically with either amiodarone or sotalol. In patients with CAD in whom SMVT recurs while on amiodarone treatment, catheter ablation is recommended over escalation of AAD therapy. In the VANISH trial, the composite endpoint of death, VT storm, and appropriate ICD therapy was reached significantly less often in the ablation group as compared to the escalated amiodarone-therapy group over a mean follow-up of 28 months (59% vs. 68.5%; HR 0.72; 95% CI 0.53– 0.98; P = 0.04). The ongoing VANISH2 trial (ClinicalTrials.gov Identifier: NCT02830360) addresses the question of whether catheter ablation as first-line treatment is superior to AAD therapy in post-MI patients with SMVT.

Preventive VT ablation after a first documented SMVT, which was followed by ICD implantation, reduced neither mortality nor hospitalizations for arrhythmia or worsening heart failure when compared to a deferred ablation strategy only after the third ICD shock.

7.1.1.4. Coronary anomalies

Anomalous aortic origin of a coronary artery, either the left or the right, arising from the opposite sinus of Valsalva, is associated with an increased risk of SCD, especially in individuals,35 years during or following vigorous exercise. Anomalous aortic origin of the left coronary artery is less common but more malignant than anomalous aortic origin of the right coronary artery. Other risk factors for SCD are interarterial course between the aorta and pulmonary artery, slit-like shaped orifice, high orifice, acuteangle take-off, and intramural course and its length. Indications for surgical intervention, especially in asymptomatic patients, are based on the evaluation of high-risk anatomy by CTA and the assessment of exercise-induced ischaemia using advanced imaging modalities. Cardiac stress imaging is also indicated to evaluate exercise-induced ischaemia after surgical intervention, especially in patients with an aborted CA.

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Recommendation Table 25 — Recommendations for sudden cardiac death prevention in patients with coronary anomalies

Recommendations	Classa	Levelb
Diagnostic evaluation
Cardiac stress imaging during physical exercise is recommended in addition to cardiopulmonary exercise test in patients with anomalous aortic origin of a coronary artery with an interarterial course to confrm/exclude myocardial ischaemia.587	I	C
Cardiac stress imaging during physical exercise is recommended in addition to cardiopulmonary exercise test after surgery in patients with anomalous aortic origin of a coronary artery with a history of aborted CA.	I	C
Treatment
Surgery is recommended in patients with anomalous aortic origin of a coronary artery with CA, syncope suspected to be due to VAs, or angina when other causes have been excluded.585,586,588	I	C
Surgery should be considered in asymptomatic patients with anomalous aortic origin of a coronary artery and evidence of myocardial ischaemia or abnormal aortic origin of the left coronary artery with high-risk anatomy.c,585,586,588	IIa	C

CA, cardiac arrest; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence. cHigh-risk anatomy is defined as interarterial course, slit-like shaped orifice, high orifice, acute-angle take-off, and intramural course and its length.

7.1.2. Idiopathic premature ventricular complexes/ ventricular tachycardia and premature ventricular complex-induced cardiomyopathy

7.1.2.1. Idiopathic premature ventricular complexes/ventricular tachycardia

PVCs/VT in patients without SHD are defined as idiopathic (Figure 17). In patients with presumed idiopathic PVCs/VT based on a negative history and normal physical examination, 12-lead ECG and transthoracic echocardiography are important first diagnostic steps to exclude underlying SHD. Twenty-four-hour ECG Holter monitoring is usually performed to determine the PVC burden. Multiform PVCs at prolonged ECG monitoring and subtle changes on ECG or echocardiography need to be recognized. CMR should be performed whenever ECG and echocardiography are inconclusive to rule out SHD, or the clinical presentation raises suspicion for SHD.

Patients need to be treated when PVCs/VT are symptomatic or associated with deterioration of cardiac function. The clinical course and responses to different treatments have been mostly studied in those originating from the RVOT or the left fascicles.

Several drugs have been used to treat idiopathic PVCs/VT. Recommendations are based on small or non-controlled series. Beta-blockers and CCBs are the most-studied drugs and both have been shown to be effective at arrhythmia suppression. The evidence for flecainide is scarce. In case of a higher burden of PVCs with higher heart rate or during exercise, beta-blockers should be preferred. If there is not such a correlation, the use of flecainide or CCB drugs have been associated with more effective PVC suppression. Beta-blockers should also be selected when a focal triggered activity mechanism is suspected. CCB should be the drug of choice for fascicular PVC/VT. Although data are lacking, betablockers or CCBs are considered first choice for PVCs with an origin outside the RVOT or the left fascicles because flecainide may have proarrhythmic side effects. Amiodarone is associated with severe systemic toxicity and should be used only if ablation or other drugs fail or cannot be used. A summary of the recommendations for the treatment of idiopathic PVCs/VT and PVC-induced or aggravated cardiomyopathy with AADs is provided in Table 9.

A high success rate of catheter ablation of idiopathic PVCs/VT has been reported with rare complications, particularly for the RVOT and fascicular types. In a randomized study including patients with RVOT PVCs, ablation was superior to AAD therapy for arrhythmia suppression with no differences in complications. Ablation is therefore recommended as the first-line therapy for RVOT and fascicular PVCs/VT. The available information for other forms of idiopathic PVCs/VT is limited and mostly restricted to the acute success of ablation, which, in general, is lower and associated with more recurrences than for RVOT and fascicular PVCs/VT. In addition, access to and ablation at specific locations (e.g. sinus of Valsalva, LV summit) may increase the risk for procedural complications. Therefore, when the 12-lead ECG is highly suspicious of a PVC/VT source outside the RVOT or left fascicles, the level of recommendation for ablation is lower.

In general, treatment of children should be similar to that of adults. However, ablation should be deferred in young and small children due to the risk of complications and the relatively larger size of the ablation lesion as compared to the child’s heart. Verapamil is not recommended as the first-line therapy in children,1 year old because it has been associated with hypotension in some case reports. Of note, all reported patients had either heart failure, overdosing of verapamil, or other concurrent AADs at the time verapamil was given.

Patients may present with asymptomatic frequent PVCs/VTs. Only a minority of patients with.1000 PVCs per day will develop ventricular dysfunction after 5 years follow-up. A PVC burden of 10% seems to be the minimal threshold for development of LV dysfunction, with higher risk when the PVC burden is.20%. Regular assessment of LVEF in this setting is therefore indicated. To date, there are no data supporting the benefit of arrhythmia treatment for asymptomatic patients with preserved ventricular function. In addition, PVC burden often decreases spontaneously over time, particularly in children. In selected patients, e.g. patients who do not want to be followed, catheter ablation may be considered. In patients with PVC burden, 10%, reevaluation may be appropriate in case of development of new symptoms or change in patient condition.

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----- Start of picture text ----- Patient with PVCs / Monomorphic VT and non-apparent SHDa ECG, Holter, and echocardiogram Assessment Inconclusive or atypical presentationb CMR (Class IIa) Assessment Structural abnormal heart Structural normal heart Go to flowchart PVC-induced SHD or PVC-induced cardiomyopathy Idiopathic PVC/ VT ca r diomyopathy (Figure 18) Dischargee N Symptomsc N Y >10% PVCs N >20% PVCs R V O T / Fascicular PVC/VTd Y Y Y N Regular Regular Catheter ablation Beta-bloc k e r or CCB f ollow-up L VEF f ollow-up L VEF (Class I) (Class I) (Class I) (Class I) Beta-bloc k ers, Flecainide CCB or (Class IIa) Catheter ablation Flecainide Catheter ablation (Class IIb) (Class IIa) (Class IIa) ----- End of picture text -----

Figure 17 Algorithm for the management of patients with idiopathic premature ventricular complexes/ventricular tachycardia and non-apparent structural heart disease. CCB, calcium channel blocker; CMR, cardiac magnetic resonance; ECG, electrocardiogram; LVEF, left ventricular ejection fraction; N, No; PVC, premature ventricular complex; RVOT, right ventricular outflow tract; SHD, structural heart disease; VT, ventricular tachycardia; Y, Yes.[a] Non-apparent SHD is defined by lack of significant abnormalities in physical examination, basal ECG, and echocardiogram.[b] Atypical presentation: e.g. older age, right bundle branch block morphology, sustained monomorphic VT consistent with re-entry.[c] Symptoms should be relevant and related to PVC/VT.[d] Origin suspected by ECG or confirmed during electrophysiological evaluation.[e] Consider re-evaluation in case of new symptoms or changes in patient clinical condition.

Table 9 Summary of the recommendations for the treatment of patients with frequent idiopathic premature ventricular complexes/ventricular tachycardia or premature ventricular complex-induced cardiomyopathy

	Ablation	Beta-blocker	CCB	Flecainide	Amiodarone	© ESC 2022
RVOT/fascicular PVC/VT: Symptomatic, normal LV function	Class I	Class IIa	Class IIa	Class IIa	Class III
PVC/VT other than RVOT/fascicular: Symptomatic, normal LV function	Class IIa	Class I	Class I	Class IIa	Class III
RVOT/fascicular PVC/VT: LV dysfunction	Class I	Class IIa	Class IIIa	Class IIab	Class IIa
PVC/VT other than RVOT/fascicular: LV dysfunction	Class I	Class IIa	Class IIIa	Class IIab	Class IIa
PVC: Burden.20%, asymptomatic, normal LV function	Class IIb				Class III

CCB, calcium channel blocker; LV, left ventricular; PVC, premature ventricular complex; RVOT, right ventricular outflow tract; VT, ventricular tachycardia. aIntravenous calcium channel blockers. bIn selected patients (only moderate LV dysfunction).

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Recommendation Table 26 — Recommendations for the management of patients with idiopathic premature ventricular complexes/ventricular tachycardia

Recommendations	Classa	Levelb
General recommendations
Regular assessment of ventricular function of patients with PVC burden.10% and normal ventricular function is indicated.602,603	I	C
In patients with PVCs/VT and a presentation not typical for an idiopathic origin,c CMR should be considered, despite a normal echocardiogram.195	IIa	C
Treatment
Catheter ablation asfrst-line treatment is recommended for symptomatic idiopathic VT/ PVCs from the RVOT or the left fascicles.d,535,595,596,604	I	B
Beta-blockers or non-dihydropyridine CCBs are indicated in symptomatic patients with idiopathic VT/PVCs from an origin other than the RVOT or the left fascicles.304,593	I	C
Beta-blockers, non-dihydropyridine CCBs, or fecainide should be considered when catheter ablation is not available, desired, or is particularly risky in symptomatic patients with idiopathic VT/ PVCs from the RVOT or the left fascicles.304,592,593	IIa	B
Catheter ablation orfecainide should be considered in symptomatic patients with idiopathic VT/PVCs from an origin other than the RVOT or the left fascicles.535,604,605	IIa	C
Catheter ablation may be considered for idiopathic VT/PVCs in asymptomatic patients with repeatedly more than 20% of PVCs per day at follow-up.535,600,601	IIb	B
Catheter ablation of idiopathic VT/PVCs is not recommended in children,5 years of age or,10 kg weight except when previous medical therapy fails or when VT is not haemodynamically tolerated.597	III	C
Amiodarone as afrst-line treatment is not recommended in patients with idiopathic VTs/ PVCs.594	III	C
Verapamil is not recommended in children,1 year of age with PVC/VT, particularly if they have signs of heart failure or concurrent use of other AADs.606	III	C

AAD, anti-arrhythmic drug; CCB, calcium channel blocker; CMR, cardiac magnetic resonance; PVC, premature ventricular complex; RVOT, right ventricular outflow tract; SMVT, sustained monomorphic ventricular tachycardia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cIncluding but not limited to older age, right bundle branch block (RBBB) morphology, SMVT consistent with re-entry. dLevel of evidence C for VT/PVCs from left fascicles.

7.1.2.2. Premature ventricular complex-induced/-aggravated cardiomyopathy

The importance of PVC-induced cardiomyopathy as a secondary and reversible cause of LV dysfunction in patients without SHD has been recognized. The patient’s medical and family history, 12-lead ECG, Holter-ECG, and echocardiography form the cornerstones of the evaluation of patients with suspected PVC-induced cardiomyopathy (Figure 18). PVC burden has been shown to be the strongest independent predictor of PVC-induced cardiomyopathy in several studies. Day-by-day fluctuations of PVC burden have been reported in patients undergoing 14-day monitoring, but most data are based on 24-h registrations. A PVC burden of at least 10% appears to be the minimal threshold for development of PVC-induced cardiomyopathy, and the risk increases further with a PVC burden.20%. In patients with a PVC burden,10%, other cardiomyopathy aetiologies should be suspected and further diagnostic work-up undertaken. In such patients, Holter-ECG should be repeated to assess fluctuations in PVC burden. Factors predicting adverse LV remodelling in patients with frequent PVCs include superior PVC axis, epicardial origin, NSVT, shorter coupling interval, and male gender.

Frequent PVCs can also aggravate LV dysfunction in patients with SHD. In such cases, LV dysfunction can either be a direct consequence of PVCs as in PVC-induced cardiomyopathy, or due to the limiting effect of PVCs on optimal biventricular pacing in CRT patients. Parameters such as smaller LV end diastolic diameter and shorter intrinsic QRS duration might help to distinguish PVC-induced cardiomyopathy from PVC-aggravated cardiomyopathy. CMR should be considered for patients suspected to have PVC-induced cardiomyopathy to exclude subtle forms of SHD. In a patient with frequent PVCs, the presence of LGE suggests SHD with frequent PVCs rather than PVC-induced cardiomyopathy, in which LGE is mostly absent. Given that PVCs with a RBBB morphology have been reported to show a stronger association with LGE, those patients should be particularly considered for CMR.

The diagnosis of PVC-induced cardiomyopathy vs. PVC-aggravated cardiomyopathy can be confirmed only after LVEF improvement/normalization (reverse remodelling) following suppression of the PVCs.

Catheter ablation of the PVCs is very efficient, with reported success rates of 75–90%, and is considered first-line treatment for PVC-induced cardiomyopathy. Factors affecting acute ablation success and clinical outcome include the site of origin of PVCs (highest for outflow tract PVCs), the number of PVC morphologies, and the absence of LGE on CMR. In patients with SHD, catheter ablation of frequent monomorphic PVCs has also been shown to improve LVEF in patients with both CAD and cardiomyopathies with and without CRT. Similarly, the use of anti-arrhythmic medications for PVC suppression has been shown to improve LVEF. In one RCT, amiodarone resulted in a better PVC suppression and a higher LVEF improvement compared to placebo. Sodium channel blockers can also effectively suppress PVCs. In one study, flecainide reduced the PVC burden from 36% to 10% and resulted in LVEF increase from 37% to 49%.

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----- Start of picture text ----- Patient with PVC-Burden >10% and mildly reduced or reduced L VEF N Known SHD Y (suspicious) CAD, Further evaluation L V dysfunction valvular heart disease or Y according to explained by underlying inflammatory heart disease most li k ely diagnosis heart disease N N Y CMR (Class IIa) Follow-up N LGE Y Suspected PVC induced SHD aggr a vated by cardiomyopathy frequent PVC’s Catheter ablation Catheter ablation (Class I) (Class IIa) AAD Amiodarone (Class IIa) (Class IIa) ----- End of picture text -----

Figure 18 Algorithm for the management of patients with premature ventricular complex-induced/-aggravated cardiomyopathy. AAD, anti-arrhythmic drug; CAD, coronary artery disease; CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement; LV, left ventricular; LVEF, left ventricular ejection fraction; N, No; PVC, premature ventricular complex; SHD, structural heart disease; Y, Yes.

While flecainide have a more favourable adverse effect profile regarding organ toxicity, increased mortality has previously been shown in patients with MI. For selected patients with suspected PVC-induced cardiomyopathy and PVC-aggravated cardiomyopathy, flecainide can still be considered, particularly if an ICD is in place (Table 9).

A rare monogenetic cause of PVC-induced cardiomyopathy, referred to as multifocal ectopic Purkinje-related premature contractions, has been reported. It is characterized by a DCM phenotype and the presence of numerous PVCs with RBBB and/or left bundle branch block (LBBB) morphologies and an increased risk of SCD. Pathogenic mutations in the SCN5A gene lead to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular Purkinje system. Limited data suggest that patients with multifocal ectopic Purkinje-related premature contractions do not respond to beta-blockers but might benefit from therapy with flecainide, quinidine, or amiodarone.

Recommendation Table 27 — Recommendations for the management of patients with premature ventricular complex-induced or premature ventricular complexaggravated cardiomyopathy

Recommendation	Classa	Levelb
Diagnostic evaluation
In patients with an unexplained reduced EF and a PVC burden of at least 10%, PVC-induced cardiomyopathy should be considered.600,609,610	IIa	C
In patients with suspected PVC-induced cardiomyopathy, CMR should be considered.590,615	IIa	B
Treatment
In patients with a cardiomyopathy suspected to be caused by frequent and predominately monomorphic PVCs, catheter ablation is recommended.535,600,609,612,617,618,620	I	C

Continued

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In patients with a cardiomyopathy suspected to be caused by frequent and predominately monomorphic PVCs, treatment with AADsc should be considered if catheter ablation is not desired, suspected to be high-risk, or unsuccessful.624,626	IIa	C	© ESC 2022
In patients with SHD in whom predominately monomorphic frequent PVCs are suspected to be contributing to the cardiomyopathy, AAD (amiodarone) treatment or catheter ablation should be considered. 617,621,622,624	IIa	B
In non-responders to CRT with frequent, predominately monomorphic PVCs limiting optimal biventricular pacing despite pharmacological therapy, catheter ablation or AADs should be considered.623	IIa	C

AAD, anti-arrhythmic drug; CMR, cardiac magnetic resonance; CRT, cardiac resynchronization therapy; EF, ejection fraction; ICD, implantable cardioverter defibrillator; LV, left ventricular; PVC, premature ventricular complex; SHD, structural heart disease. aClass of recommendation. bLevel of evidence. cFlecainide only in selected patients (ICD recipients, only moderate LV dysfunction).

7.1.3. Cardiomyopathies

7.1.3.1. Dilated cardiomyopathy and hypokinetic non-dilated cardiomyopathy

DCM is characterized by LV dilatation and systolic dysfunction unexplained by CAD or abnormal loading conditions. The true prevalence is difficult to estimate. Older studies reported a prevalence of 1 in 2700 individuals.

Historic data in adults with DCM showed a 1-year mortality of 20–25% and a 50% survival at 5 years. Recent trials of DCM patients with systolic heart failure and OMT report 5-year mortality rates in the range of 21–28%. SCD occurs in up to 12% of patients with DCM and still accounts for 25–35% of all deaths.

In children, the annual incidence of DCM is 0.57 cases per 100 000. The prognosis in children is poor, with a 5-year incidence of heart transplantation or heart failure-related death of 40%. However, in contrast to adults, the incidence of SCD in paediatric DCM patients is much lower, with a 5-year incidence of 2.4–3% as reported in two large paediatric cardiomyopathy registries from the United States and Australia.

Causes of DCM can be genetic or acquired. Genetic predisposition may also interact with extrinsic factors such as in peri-partum, alcoholic, or chemotherapy-related cardiomyopathies. The phenotype, particularly of genetic aetiologies, can change over time and/or may not meet standard disease criteria at the time of disease manifestation. As a consequence, a new category of a hypokinetic non-dilated cardiomyopathy (HNDCM) has been proposed.

7.1.3.1.1. Diagnostic evaluation and risk stratification. An algorithm for risk stratification and primary prevention of SCD in patients with DCM/HNDCM is presented in Figure 19.

Careful diagnostic work-up, including genetic testing and CMR, should be considered to identify the underlying cause for aetiology-oriented risk stratification and treatment.

Pathogenic mutations are identified in 25–55% of DCM patients, most often with autosomal dominant inheritance. Truncated mutations in the titin gene (TTN) are most frequently found, followed by LMNA, sarcomeric, and desmosomal mutations. Mutations in genes such as LMNA, PLN, RBM20, and FLNC are associated with a higher risk of VA and SCD. Carriers of desmosomal and LMNA variants experienced the highest rate of VA/SCD, which was independent of the LVEF in one series.

The yield of genetic testing is particularly high in DCM patients with familial forms of DCM or SCD in a first-degree relative at younger age. An inherited DCM is also more likely in patients who present at young age or with signs suspicious for a specific aetiology (e.g. prolonged AV conduction for LMNA) (Figure 20). First-degree relatives of DCM/HNDCM patients should undergo clinical diagnostic evaluation, especially if an inherited cause is suspected.

Discrimination between high- and low-risk patients for SCD remains challenging. Beyond LVEF and NYHA class, recent data suggest that both genetic and CMR findings can contribute to risk stratification. A meta-analysis of 29 studies combining 2948 patients studied the role of CMR in patients with DCM. LGE was significantly associated with the arrhythmic endpoint, even when including only studies that performed multivariate analysis (HR 6.7; P, 0.001). Interestingly, the association between LGE and the arrhythmic endpoint remained significant among patients with mean LVEF.35%. Similarly, a recent study of 1020 consecutive patients with DCM and CMR observed that LGE and LVEF were both risk markers for all-cause mortality and cardiac death, but only LGE was significantly associated with SCD risk.

SCD risk stratification has been refined in the subgroup of patients with LMNA mutations, which represent 5–10% of all DCM patients. LMNA mutations are associated with early atrial and ventricular arrhythmias, premature conduction disease, a high risk of SCD, and progression to end-stage heart failure. In a multicentre registry of 269 LMNA mutation carriers, NSVT, LVEF,45% at first evaluation, male sex, and non-missense mutations were identified as independent risk factors for VA. VA occurred only in persons with at least two of these risk factors. The risk stratification was subsequently externally validated. Another study, which involved 589 LMNA mutation carriers, identified AV block as an additional predictor. Recently a risk calculator has been developed (https://lmna-riskvta.fr/) to predict the risk of life-threatening VA (C-index of 0.776 [95% CI: 0.711–0.842]). In patients with a 5-year estimated risk ≥10% and a manifest cardiac phenotype (NSVT, LVEF, 50%, or AV conduction delay), a primary prevention ICD implantation should be considered to avoid potential over-implantation in mutation carriers without a cardiac phenotype. In LMNA mutation carriers with a DCM phenotype, high-intensity exercise has been associated with a high risk of SCD and impaired LVEF and is therefore not recommended.

A risk score for VA prediction has been recently proposed for patients with DCM or ARVC related to the p.Arg14del mutation in the PLN gene. Validation studies are needed before it can be recommended for clinical use.

Beyond genetics and CMR, additional SCD predictors have been suggested, often derived from small cohorts with no or few replication studies. An unexplained syncope requires further evaluation and PES may determine the underlying cause. The risk for arrhythmic

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----- Start of picture text ----- Patient with DCM/HNDCM CMR (Class IIa) Go to specific sections Suspicious of cause requiring specific treatment Y for specific aetiology-directed management, especially for inflammatory diseases N Family history of DCM/HNDCM or family history of SCD (<50 y, first-degree relative) or AV block <50 y N Y 5-year risk ofVA ≥10% Genetic testing Pathogenic and LVEF <50% (Class IIa) (Class I) mutation LMNA or NSVT or AV conduction delay N Y ≤35% LVEF 36–50% Annual ICD implantation reevaluation (Class IIa) ICD implantation ≥2 risk factors [a] (Class IIa) N Y N Unexplained syncope ICD implantation (Class IIa) Y Follow-up ILR [b ] (Class I) PES (Class IIa) N SMVT inducible Y ICD implantation (Class IIa) ----- End of picture text -----

Figure 19 Algorithm for risk stratification and primary prevention of sudden cardiac death in patients with dilated cardiomyopathy/hypokinetic nondilated cardiomyopathy. AV, atrioventricular; CMR, cardiac magnetic resonance; DCM, dilated cardiomyopathy; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; LMNA: lamin A/C gene; LVEF, left ventricular ejection fraction; N, No; NSVT, non-sustained ventricular tachycardia; PES, programmed electrical stimulation; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmias; Y, Yes.[a] Risk factors: unexplained syncope, pathogenic variants in PLN, FLNC, or RBM20, LGE on CMR, inducible SMVT at PES.[b] The 2018 ESC Guidelines for the diagnosis and management of syncope.

events in DCM patients with a low LVEF and an unexplained syncope was similar to those with prior CA and high, independent from the outcome of PES. However, data in DCM patients with a mildly reduced EF suggest an incremental value of PES. Among DCM patients with an EF ≥40% and an unexplained syncope, who underwent ICD implantation after a positive PES, 80% had appropriate ICD therapy during follow-up. No SCD or symptomatic VA occurred in non-inducible patients.

7.1.3.1.2. Primary prevention of sudden cardiac death. In patients with DCM/HNDCM, OMT according to current 2021 ESC

Guidelines for the diagnosis and treatment of acute and chronic heart failure is mandatory. Re-evaluation of cardiac function and clinical status after 3 months’ OMT is required before primary prevention ICD implantation. LV function is more likely to improve in DCM caused by myocarditis or TTN mutations.

The efficacy of primary prevention ICDs in DCM patients with HFrEF has been addressed in six RCTs.

Five studies were published between 2002 and 2005 (CAT, AMIOVIRT, DEFINITE, COMPANION, and SCD-HeFT). The first three were smaller studies enrolling only DCM patients, whereas SCD-HeFT and COMPANION were larger and

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----- Start of picture text ----- ECG sinus rhythm – Small amplitude P waves and first degree AV block I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 ECG VT – RBBB-like, inferior axis (LV summit origin) I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 CMR – Mid-wall septal LGE 4-chamber Short axis ----- End of picture text -----

Figure 20 Typical features of dilated cardiomyopathy associated with lamin A/C gene mutation with ventricular arrhythmias. AV, atrioventricular; CMR, cardiac magnetic resonance; ECG, electrocardiogram; LGE, late gadolinium enhancement; LV, left ventricle; RBBB, right bundle branch block; VT, ventricular tachycardia.

included patients with CAD and DCM. The COMPANION study differed from the others as it compared CRT-defibrillator, CRT-pacemaker, and OMT. A meta-analysis of the five trials (1854 patients with DCM) demonstrated a 31% reduction in allcause mortality with ICD relative to medical therapy (RR 0.69 [95% CI 0.55, 0.87], P, 0.002). This effect persisted when COMPANION was excluded.

More recently, the DANISH trial enrolled 1116 symptomatic patients (NYHA class II or III) with non-ischaemic systolic heart failure (LVEF ≤ 35%). Patients were randomized to ICD or no ICD after OMT. No reduction in the primary endpoint of all-cause death for patients

randomized to ICD therapy (HR 0.87; 95% CI 0.68–1.12; P = 0.28) was observed, despite a significant reduction in SCD in the ICD group (HR 0.50; 95% CI 0.31–0.82; P = 0.005). Potential explanations are the low SCD rate in the trial (4.3% in the ICD group and 8.2% in the control group), the excellent medical treatment (.90% of patients on ACE inhibitors and beta-blockers,.50% on MRA), and the high prevalence (58%) of CRT. A meta-analysis of all six primary prevention trials still demonstrated a reduction, although lower, in overall mortality with ICD therapy (RR 0.76; 95% CI 0.65–0.91; P = 0.002). In a sensitivity analysis, the benefit of ICD therapy was maintained after the removal of any single study from the pooled analysis.

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The results of the DANISH trial emphasize the need for further refining the indication for primary prevention ICDs in contemporary DCM patients. Age and comorbidity need to be considered. - In the DANISH trial, ICD implantation was associated with a signifi cantly lower rate of death in younger patients. A further analysis of the DANISH data showed an association between reduced all-cause mortality and ICDs in patients ≤70 years of age (HR, 0.70; 95% CI 0.51–0.96; P = 0.03), but not in patients.70 years of age.

Prospective studies evaluating the benefit of ICDs in DCM/ HNDCM patients with intermediate LV dysfunction, but with risk factors that have been associated with VA and SCD (including LGE on CMR, pathogenic mutations in PLN, FLNC, RBM20, unexplained syncope, and inducibility of SMVT), are lacking. Given the limitation of LVEF as the only risk marker in DCM/HNDCM, this panel of experts shares the opinion that in the presence of a combination of risk markers an ICD should be considered.

7.1.3.1.3. Secondary prevention of sudden cardiac death and management of ventricular arrhythmias. Three randomized trials (AVID, CASH, and CIDS) have compared ICD therapy and medical treatment for secondary prevention in patients after aborted CA or not-tolerated VT. The three trials enrolled a total of 1963 patients, of whom only 292 (14.8%) had non-ischaemic aetiologies. A significant reduction in death from any cause in patients with ICDs was demonstrated, which was almost entirely due to a 50% reduction in arrhythmic death. In the subgroup of patients with cardiomyopathies there was a similar but non-significant trend in the reduction of death. RCTs have excluded patients with haemodynamically tolerated VT. In DCM patients the VT substrate is less well defined, and disease progression needs to be considered. Therefore, despite the lack of data, this panel of experts shares the opinion that an ICD should also be considered in DCM patients with haemodynamically tolerated VT.

Optimization of ICD programming (see Section 6.2.3.1) can reduce ICD shocks delivered in response to VT, but additional therapy to reduce symptomatic VA episodes is often required. In the OPTIC trial, 412 patients with ICD implantation within 21 days of VT/VF were randomized to amiodarone plus beta-blockers, sotalol alone, or beta-blocker alone. ICD shock rates after one year were 10.3%, 24.3%, and 38.5%, respectively. The higher efficacy of amiodarone plus beta-blockers compared to sotalol needs to be weighed against the higher rate of medication-related adverse events on an individual basis. Although only limited data are available, sodium channel blockers may control VT in SHD and may be beneficial in ICD recipients without advanced heart failure. The majority of SMVT is due to scar-related re-entry, which can be targeted by catheter ablation. Acute ablation outcome has been reported to be similar for CAD and DCM. However, VT recurrence rates are usually higher in DCM patients (VT-free survival 40.5% in DCM vs. 57% in CAD at 1 year). After multiple procedures in 36% of the patients, longterm freedom of VT could be achieved in 69% of cases in a retrospective, single-centre cohort of 282 patients treated between 1999 and 2014.

– Epicardial ablation is needed in 27 30% of the procedures. Outcome is particularly poor, and bailout strategies (transcoronary

ethanol ablation, bipolar ablation, surgical ablation) may be required in patients with pathogenic mutations (LMNA gene) and in those with deep intramural, anteroseptal substrate locations. Considering the complexity of the ablation procedure, DCM patients should therefore be treated only in specialized centres.

Recommendation Table 28 — Recommendations for risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmias in dilated cardiomyopathy/hypokinetic non-dilated cardiomyopathy

Recommendation	Classa	Levelb
Diagnostic evaluation and general recommendations
Genetic testing (including at leastLMNA,PLN, RBM20, andFLNCgenes) is recommended in patients with DCM/HNDCM and AV conduction delay at,50 years, or who have a family history of DCM/HNDCM or SCD in afrst-degree relative (at age,50 years).641–645	I	B
CMR with LGE should be considered in DCM/ HNDCM patients for assessing the aetiology and the risk of VA/SCD.129,651,667	IIa	B
Genetic testing (including at leastLMNA,PLN, RBM20, andFLNCgenes) should be considered for risk stratifcation in patients with apparently sporadic DCM/HNDCM, who present at young age, or with signs suspicious for an inherited aetiology.641–645	IIa	C
Participation in high-intensity exercise including competitive sports is not recommended for individuals with DCM/HNDCM and aLMNA mutation.655	III	C
Risk stratifcation and primary prevention of SCD
ICD implantation should be considered in patients with DCM/HNDCM, symptomatic heart failure (NYHA class II–III), and LVEF≤35% after≥3 months of OMT.357,359,635,650	IIa	A
ICD implantation should be considered in DCM/ HNDCM patients with a pathogenic mutation in LMNAgene, if the estimated 5-year risk of life-threatening VA is≥10%c andin the presence of NSVT or LVEF,50% or AV conduction delay.80,652,653	IIa	B
ICD implantation should be considered in DCM/ HNDCM patients with a LVEF,50% and≥2 risk factors (syncope, LGE on CMR, inducible SMVT at PES, pathogenic mutations inLMNA,d PLN,FLNC, andRBM20genes).	IIa	C
In DCM/HNDM patients, electrophysiological evaluation should be considered when syncope remains unexplained after non-invasive evaluation.661,668	IIa	C

Continued

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Secondary prevention of SCD and treatment of VAs ICD implantation is recommended in patients with DCM/HNDCM, who survive SCA due to VT/ VF or experience haemodynamically not-tolerated SMVT.349,351,352 I B Catheter ablation in specialized centres should be considered in patients with DCM/HNDCM and recurrent, symptomatic SMVT or ICD shocks for SMVT, in whom AADs are ineffective, contraindicated, or not tolerated.481,497,664,669 IIa C The addition of oral amiodarone or replacement of beta-blockers by sotalol should be considered in patients with DCM/HNDCM and an ICD who experience recurrent, symptomatic VA despite optimal device programming and beta-blocker treatment.318 IIa B ICD implantation should be considered in patients with DCM/HNDCM and haemodynamically tolerated SMVT. IIa C Management of relatives of a patient or SCD victim with DCM/HNDCM In afrst-degree relative of a DCM/HNDCM patient, an ECG and an echocardiogram are recommended if: •theindexpatientwasdiagnosed,50yearsofageor hasclinicalfeaturessuggestiveofaninheritedcause,or •there is family history of DCM/HNDCM, or premature unexpected SD.646 I C In afrst-degree relative of a patient with apparently sporadic DCM/HNDCM, an ECG and an echocardiogram may be considered.646 IIb C © ESC 2022	Secondary prevention of SCD and treatment of VAs ICD implantation is recommended in patients with DCM/HNDCM, who survive SCA due to VT/ VF or experience haemodynamically not-tolerated SMVT.349,351,352 I B Catheter ablation in specialized centres should be considered in patients with DCM/HNDCM and recurrent, symptomatic SMVT or ICD shocks for SMVT, in whom AADs are ineffective, contraindicated, or not tolerated.481,497,664,669 IIa C The addition of oral amiodarone or replacement of beta-blockers by sotalol should be considered in patients with DCM/HNDCM and an ICD who experience recurrent, symptomatic VA despite optimal device programming and beta-blocker treatment.318 IIa B ICD implantation should be considered in patients with DCM/HNDCM and haemodynamically tolerated SMVT. IIa C Management of relatives of a patient or SCD victim with DCM/HNDCM In afrst-degree relative of a DCM/HNDCM patient, an ECG and an echocardiogram are recommended if: •theindexpatientwasdiagnosed,50yearsofageor hasclinicalfeaturessuggestiveofaninheritedcause,or •there is family history of DCM/HNDCM, or premature unexpected SD.646 I C In afrst-degree relative of a patient with apparently sporadic DCM/HNDCM, an ECG and an echocardiogram may be considered.646 IIb C © ESC 2022	Secondary prevention of SCD and treatment of VAs ICD implantation is recommended in patients with DCM/HNDCM, who survive SCA due to VT/ VF or experience haemodynamically not-tolerated SMVT.349,351,352 I B Catheter ablation in specialized centres should be considered in patients with DCM/HNDCM and recurrent, symptomatic SMVT or ICD shocks for SMVT, in whom AADs are ineffective, contraindicated, or not tolerated.481,497,664,669 IIa C The addition of oral amiodarone or replacement of beta-blockers by sotalol should be considered in patients with DCM/HNDCM and an ICD who experience recurrent, symptomatic VA despite optimal device programming and beta-blocker treatment.318 IIa B ICD implantation should be considered in patients with DCM/HNDCM and haemodynamically tolerated SMVT. IIa C Management of relatives of a patient or SCD victim with DCM/HNDCM In afrst-degree relative of a DCM/HNDCM patient, an ECG and an echocardiogram are recommended if: •theindexpatientwasdiagnosed,50yearsofageor hasclinicalfeaturessuggestiveofaninheritedcause,or •there is family history of DCM/HNDCM, or premature unexpected SD.646 I C In afrst-degree relative of a patient with apparently sporadic DCM/HNDCM, an ECG and an echocardiogram may be considered.646 IIb C © ESC 2022
ICD implantation is recommended in patients with DCM/HNDCM, who survive SCA due to VT/ VF or experience haemodynamically not-tolerated SMVT.349,351,352	I	B
Catheter ablation in specialized centres should be considered in patients with DCM/HNDCM and recurrent, symptomatic SMVT or ICD shocks for SMVT, in whom AADs are ineffective, contraindicated, or not tolerated.481,497,664,669	IIa	C
The addition of oral amiodarone or replacement of beta-blockers by sotalol should be considered in patients with DCM/HNDCM and an ICD who experience recurrent, symptomatic VA despite optimal device programming and beta-blocker treatment.318	IIa	B
ICD implantation should be considered in patients with DCM/HNDCM and haemodynamically tolerated SMVT.	IIa	C
Management of relatives of a patient or SCD victim DCM/HNDCM
In afrst-degree relative of a DCM/HNDCM patient, an ECG and an echocardiogram are recommended if: •theindexpatientwasdiagnosed,50yearsofageor hasclinicalfeaturessuggestiveofaninheritedcause,or •there is family history of DCM/HNDCM, or premature unexpected SD.646	I	C
In afrst-degree relative of a patient with apparently sporadic DCM/HNDCM, an ECG and an echocardiogram may be considered.646	IIb	C

AAD, anti-arrhythmic drug; AV, atrioventricular; CMR, cardiac magnetic resonance; DCM, dilated cardiomyopathy; ECG, electrocardiogram; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; OMT, optimal medical therapy; PES, programmed electrical stimulation; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SD, sudden death; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cBased on the risk calculator https://lmna-risk-vta.fr/ dSee specific recommendations for LMNA.

7.1.3.2. Arrhythmogenic right ventricular cardiomyopathy

ARVC is an inherited disease characterized by fibrofatty myocardial replacement. The prevalence ranges from 1:1000 to 1:5000 individuals, with male predominance among probands. Patients with SCD/VF at first presentation are typically younger (median age 23 [range 13–57]) compared to those who present with a SMVT (median age 36 years [range 14–78]).

ARVC is caused by pathogenic mutations in desmosomal genes and less commonly in non-desmosomal genes. Genetic testing is indicated and identification of a mutation (in up to 73% of probands) is a major criterion for the diagnosis. In 4–16% compound/ digenic mutations are found, which have been associated with an increased risk of VA at younger age. The disease penetrance in first-degree relatives is 28–58%, supporting regular clinical evaluation of relatives.

ARVC is characterized by a predominant RV involvement. The 2010 revised international diagnostic task force criteria are based on a multiparametric strategy (Figure 21). Tissue characterization by CMR was not included. However, RV fatty infiltration and LV LGE are frequently observed (in 29–53% and 35.5–45% of probands, respectively) and may be present before patients meet major task force imaging criteria. Both wall motion alterations and pre-/ post-contrast signal abnormalities have been suggested to enhance the diagnostic accuracy of CMR for ARVC. The identification of biventricular and left-dominant involvement in ARVC patients has recently led to the proposed term ‘arrhythmo’ genic cardiomyopathy.

Restriction from high-intensity exercise is regarded as a preventive tool in clinically affected ARVC patients to reduce the risk of VAs and disease progression. Whether sport restriction is beneficial in all mutation carriers without disease expression has not been evaluated in prospective cohorts, but avoidance of competitive, highintensity exercise seems to be reasonable. SCD and VA occur disproportionately during exercise in affected patients, and high-dose isoproterenol infusion may provoke PVT in.90% of ARVC patients, supporting the role of sympathetic stimulation for arrhythmogeneity. Whether beta-blockers can prevent spontaneous VA is, however, unclear. Limited data suggest a potential beneficial role of atenolol.

7.1.3.2.1. Risk stratification. In ARVC patients not implanted with ICDs, CA occurs in 4.6–6.1%, while 23% of patients experience a non-fatal SMVT during an average follow-up of 8–11 years. Whether a SMVT is acutely life-threatening depends on the VT cycle length, cardiac function, and the circumstances under which VT occurs. Among definite/probable ARVC patients considered at high risk – for VA, 23 48% will experience appropriate ICD intervention during – a mean follow-up of 4.7 years. In 16 19% of cases, ICD intervention is triggered by fast VT ≥250 b.p.m. or VF, which is considered as surrogate for a life-threatening event. In a large cohort of 864 ARVC patients (38.8% with a prior VA), 43% had VT/VF during a median follow-up of 5.75 years, but only 10.8% a potentially lifethreatening event. Thus, in 3 out of 4 ARVC patients, ICD therapy is appropriate but may not be considered acutely life-saving. This is relevant because risk prediction algorithms and models are based on combined arrhythmic endpoints, which are often equated with ICD indications to prevent SCD. This is particularly important for the young ARVC patients with a lifetime risk of ICD-related complications.

Randomized studies of ICD therapy for secondary prevention are lacking, but the high rates of appropriate ICD therapy triggered by fast VT/VF episodes in patients implanted after CA or haemodynamically poorly tolerated VT strongly suggest a survival benefit from ICD. In patients who present with a haemodynamically tolerated VT, the survival benefit from ICD is less clear. Identification of ARVC patients at risk for SCD is difficult, and the evidence supporting risk factors for life-threatening VAs is limited. Arrhythmic syncope was a predictor for subsequent events in most series of patients with definitive ARVC (pooled HR 3.67; CI 2.75– 4.9) and, in these patients, an ICD should be considered. RV and LV dysfunction have been associated with a higher arrhythmic risk. Cut-off values are difficult to determine but, in

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----- Start of picture text ----- ECG sinus rhythm – Negative T wavesV1-V4, terminal QRS duration >55 ms I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 ECG VT – LBBB-like, superior axis (basal RV origin) I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 CMR – Dilated RV with basal aneurysm 4-chamber 3-chamber Short axis ----- End of picture text -----

Figure 21 Typical features of arrhythmogenic right ventricular cardiomyopathy associated with ventricular arrhythmias. CMR, cardiac magnetic resonance; ECG, electrocardiogram; LBBB, left bundle branch block; RV, right ventricle; VT, ventricular tachycardia.

patients with severe RV dysfunction (RV fractional area change ≤17% or RV ejection fraction ≤35%), an ICD should be considered. Likewise, ARVC patients with significant LV involvement (LVEF ≤ 35%) should be treated according to the current DCM recommendation regarding ICD implantation. There are conflicting data on the independent predictive value of NSVT for subsequent sustained arrhythmic events. Likewise, the role of PES in risk stratification, particularly in asymptomatic patients, is not well defined. In one series including mainly symptomatic patients, both NSVT and a positive PES independently predicted arrhythmic events, while others report a low diagnostic accuracy. Risk prediction based on a single parameter does not consider the potential combined effect and interactions between factors. Therefore,

although supporting data are lacking, this panel of experts supports that an ICD should be considered in symptomatic ARVC patients with moderate RV (,40%) and/or LV dysfunction (,45%) and who have either NSVT or have SMVT inducible at PES. An internally validated risk model has recently been developed from 528 patients with definite ARVC and no prior VA, including age, sex, arrhythmic syncope, NSVT, PVC burden, leads with T-wave inversion and RV ejection fraction, to predict any sustained VA (c-index 0.77). In addition, a prediction model for specifically life-threatening VA has been promoted based on 864 ARVC patients, with predictors including male sex, age, 24 h PVC count, and leads with T-wave inversion (c-index 0.74). However, validation studies are needed before these risk models can be recommended for clinical use.

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7.1.3.2.2. Treatment. Up to 97.4% of all VA episodes in ARVC ICD recipients are SMVT. The very high termination rate by ATP (92% of all episodes) independent from VT cycle length strongly supports devices with the capability for ATP. S-ICDs reduce lead-related complications and have been proven to effectively shock terminate VA in small cohorts of ARVC patients during short-term follow-up.

Additional treatment to supress VA is often required. Although not confirmed by clinical data, beta-blockers are recommended as first-line therapy in symptomatic patients.

Data on AADs to prevent VT recurrence are limited to small observational studies and registries. In general, AAD therapy has limited efficacy. Although sotalol was effective to prevent inducibility of VT, it did not supress clinically relevant arrhythmias. Treatment with amiodarone or class 1 drugs was associated with a trend to lower VT recurrence as compared with sotalol. The addition of flecainide to beta-blockers/sotalol was beneficial in a small cohort. Catheter ablation provides an alternative. Endocardial and adjuvant epicardial substrate ablation, if needed, has been associated with promising VT-free survival. Potential procedural risks, drug side effects, and the patient’s preference need to be taken into consideration.

Recommendation Table 29 — Recommendations for diagnostic, risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Recommendations	Classa	Levelb
Diagnostic evaluation and general recommendations
In patients with suspected ARVC, CMR is recommended.676–678	I	B
In patients with a suspected or defnite diagnosis of ARVC, genetic counselling and testing are recommended.672,673	I	B
Avoidance of high-intensity exercise is recommended in patients with a defnite diagnosis of ARVC.683–685	I	B
Avoidance of high-intensityc exercise may be considered in carriers of ARVC-related pathogenic mutations and no phenotype.683,687	IIb	C
Beta-blocker therapy may be considered in all patients with a defnite diagnosis of ARVC.	IIb	C
Risk stratifcation and primary prevention of SCD
ICD implantation should be considered in patients with defnite ARVC and an arrhythmic syncope.696,701,711–713	IIa	B
ICD implantation should be considered in patients with defnite ARVC and severe RV or LV systolic dysfunction.675,691	IIa	C
ICD implantation should be considered in symptomaticd patients with defnite ARVC, moderate right or left ventricular dysfunction, and	IIa	C

Continued

ICD implantation is recommended in ARVC patients with haemodynamically not-tolerated VT or VF.700	I	C
In patients with ARVC and non-sustained or sustained VAs, beta-blocker therapy is recommended.	I	C
In patients with ARVC and recurrent, symptomatic SMVT or ICD shocks for SMVT despite beta-blockers, catheter ablation in specialized centres should be considered.482,709,714	IIa	C
In ARVC patients with indication for ICDs, a device with the capability of ATP programming for SMVT up to high rates should be considered.698	IIa	B
ICD implantation should be considered in ARVC patients with a haemodynamically tolerated SMVT.692	IIa	C
In patients with ARVC and recurrent, symptomatic VT despite beta-blockers, AAD treatment should be considered.709,710	IIa	C
Management of relatives of a patient with ARVC
In afrst-degree relative of a patient with ARVC, ECG and echocardiogram are recommended.675	I	C

AAD, anti-arrhythmic drug; ARVC, arrhythmogenic right ventricular cardiomyopathy; ATP, anti-tachycardia pacing; CMR, cardiac magnetic resonance; ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; LV, left ventricle; NSVT, non-sustained ventricular tachycardia; PES, programmed electrical stimulation; RV, right ventricle; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cThe 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. dPresyncope or palpitations suggestive of VA.

7.1.3.3. Hypertrophic cardiomyopathy

HCM is characterized by increased LV wall thickness not explained by abnormal loading conditions (such as hypertension or valvular disease). Because the natural history and management differs according to the underlying aetiology of LVH, diagnostic work-up is of paramount importance (see Section 7.1.3.5) and includes CMR and genetic testing. HCM is usually caused by a mutation with autosomal dominant inheritance, supporting cardiac screening in first-degree relatives, in parallel with genetic testing in the index patient. A sarcomeric gene mutation is identified in 30–60%, most frequently in patients who are younger at diagnosis or with a family history of HCM.

The estimated prevalence of HCM in adults is 1 in 500. In children, the prevalence is much lower.

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Annual mortality related to HCM is 1–2% in most studies with contemporary management strategies, and may be as low as 0.5%. The annual rate of SCD or appropriate ICD therapy is about 0.8% but is largely dependent on age and risk profile. HCM patients are at risk for heart failure, AF, and stroke. Most HCM-related deaths at age ≤60 years occur suddenly, while older patients die more often of stroke or heart failure. SCD is often related to VA, which can be a consequence of ischaemia, left ventricle outflow tract (LVOT) obstruction, or supraventricular arrhythmias. SCD may also be triggered by exercise, and participation in competitive sport has been discouraged. However, recent data suggest that even vigorous

exercise in HCM patients without risk markers may not be associated with VA.

7.1.3.3.1. Risk stratification and primary prevention of sudden cardiac death. In primary prevention, the challenge remains to identify the relatively small group of patients with the highest risk of SCD. NSVT is identified on continuous (24/48h) ambulatory ECG monitoring in 20–25% of patients. Its prevalence increases with age and correlates with LV wall thickness and LGE on CMR. The prognostic value of NSVT for SCD is more important in young patients (,30 years). The relation between the duration, frequency, or rate of NSVT and HCM prognosis remains unclear.

----- Start of picture text ----- ECG sinus rhythm – Negative T wavesV2-V6 and inferior leads I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 ECG VT – RBBB-like, superior axis (apical LV origin) I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 CMR – Apical aneurysm with LGE 4-chamber 2-chamber ----- End of picture text -----

Figure 22 Typical features of hypertrophic cardiomyopathy associated with sustained monomorphic ventricular tachycardia. CMR, cardiac magnetic resonance; ECG, electrocardiogram; LGE, late gadolinium enhancement; LV, left ventricular; RBBB, right bundle branch block; VT, ventricular tachycardia.

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Documented NSVT during exercise test is very rare, but was associated with a higher risk of SCD. Additional risk factors have been identified and a 5-year SCD risk stratification score based on seven factors (age, LV wall thickness, LA size, LVOT gradient, NSVT, unexplained syncope, and family history of SCD) has been developed (HCM Risk-SCD: https://doc2do.com/hcm/webHCM.html) and externally validated. The calculator is not intended for use in elite athletes, or in individuals with metabolic or infiltrative diseases, or after myectomy or alcohol septal ablation.

Additional factors not captured by the Risk-SCD model should also be considered in patients with intermediate or low calculated risk, including LV systolic dysfunction, apical aneurysm, extensive LGE on CMR, and presence of single or multiple sarcomeric mutations (Figure 22). Extensive LGE on CMR defined as ≥15% of LV mass has been suggested as good predictor of SCD in adults. However, thresholds may be difficult to use because LGE quantification is dependent on CMR acquisition, type, and amount of contrast.

Periodic reassessment is mandatory as part of the longitudinal evaluation of patients. VA induced by PES is considered non-specific, although conflicting results have been reported.

In children few data on primary prevention were available until the recent development of scores and related risk calculators. The HCM Risk-Kids score has been developed and externally validated specifically in children with HCM (1–16 years of age) and includes unexplained syncope, maximal LV wall thickness, large left atrial diameter, low LVOT gradient, and NSVT (https://hcmriskkids. org). In contrast to adults, including age and family history of SCD did not improve the performance of the paediatric model. Patients with prior VF or sustained VT, known inborn errors of metabolism, and syndromic causes of HCM were excluded. The predictive value of LGE in children is less defined, although preliminary data were reported.

7.1.3.3.2. Treatment to prevent ventricular arrhythmia recurrence. Patients surviving a CA due to VT/VF or haemodynamically not-tolerated VT remain at high risk for future life-threatening VA, and will benefit from ICD therapy.

There are no RCTs in HCM or cohort studies supporting a significant role of drugs to prevent SCD. Amiodarone may reduce VA but with conflicting results regarding SCD prevention. Disopyramide and beta-blockers are efficient to control symptoms and LVOT obstruction, but there is no evidence that they reduce the risk of SCD. Similarly, surgical myectomy or alcohol ablation are not recommended with the aim to reduce risk of SCD in patients with LVOT obstruction. Following ICD implantation for primary or secondary prevention, the most common documented VA subtype is SMVT, and ATP is successful in 69–76.5% of all episodes. Although data on drug efficacy are lacking, AADs (beta-blockers, amiodarone, sotalol, sodium channel blockers) should be considered in HCM patients with symptomatic VA. Catheter ablation may also be considered in highly selected HCM patients with SMVT, in whom AADs are ineffective, contraindicated or not tolerated, as outcome after ablation is inferior compared to other non-ischaemic aetiologies.

Recommendation Table 30 — Recommendations for risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmias in hypertropic cardiomyopathy

Recommendation	Classa	Levelb
Diagnostic evaluation and general recommendations
CMR with LGE is recommended in HCM patients for diagnostic work-up.716–718	I	B
Genetic counselling and testing are recommended in HCM patients.721–725	I	B
Participation in high-intensity exercise may be considered for asymptomatic adult HCM patients without risk markers.733	IIb	C
Risk stratifcation and primary prevention of SCD
It is recommended that the 5-year risk of SCD is assessed atfrst evaluation and at 1–3-year intervals, or when there is a change in clinical status.	I	C
ICD implantation should be considered in patients aged 16 years or more with an estimated 5-year risk of SD≥6%.c,85,728,729	IIa	B
ICD implantation should be considered in HCM patients aged 16 years or more with an intermediate 5-year risk of SCD (≥4 to,6%)c and with (a) signifcant LGE at CMR (usually≥15% of LV mass); or (b) LVEF,50%; or (c) abnormal blood pressure response during exercise testd; or (d) LV apical aneurysm; or (e) presence of sarcomeric pathogenic mutation.716,717,722,736–739	IIa	B
In children less than 16 years of age with HCM and an estimated 5-year risk of SD≥6% (based on HCM Risk-Kids scoree), ICD implantation should be considered.84,742	IIa	B
ICD implantation may be considered in HCM patients aged 16 years or more with an estimated 5-year risk of SCD of≥4 to,6%.c,85,728,729	IIb	B
ICD implantation may be considered in HCM patients aged 16 years or more with a low estimated 5-year risk of SCD (,4%)c and with (a) signifcant LGE at CMR (usually≥15% of LV mass); or (b) LVEF,50%; or (c) LV apical aneurysm.716,717,722,736–739	IIb	B
Secondary prevention of SCD and treatment of VAs
ICD implantation is recommended in HCM patients with haemodynamically not-tolerated VT or VF.744–746	I	B
In patients with HCM presenting with haemodynamically tolerated SMVT, ICD implantation should be considered.	IIa	C
In patients with HCM and recurrent, symptomatic VA, or recurrent ICD therapy, AAD treatment should be considered.	IIa	C
		Continued

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Catheter ablation in specialized centres may be considered in selected patients with HCM and recurrent, symptomatic SMVT or ICD shocks for SMVT, in whom AAD are ineffective, contraindicated, or not tolerated.753,754	IIb	C
Management of relatives of a patient with HCM
In afrst-degree relative of a patient with HCM, ECG and echocardiogram are recommended.	I	C

AAD, anti-arrhythmic drug; CMR, cardiac magnetic resonance; ECG, electrocardiogram; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter defibrillator; LGE, late gadolinium enhancement; LV, left ventricle; LVEF, left ventricular ejection fraction; SCD, sudden cardiac death; SD, sudden death; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cBased on the HCM Risk-SCD: https://doc2do.com/hcm/webHCM.html dDefined as a failure to increase systolic pressure by at least 20 mmHg from rest to peak exercise, or a fall of.20 mmHg from peak pressure. eBased on the HCM kid risk score: https://hcmriskkids.org

7.1.3.4. Left ventricular non-compaction

LVNC comprises a heterogeneous group of diseases. The diagnosis is challenging, and various diagnostic criteria have been proposed. The yield of genetic tests in index patients is low.

The morphological phenotype of non-compaction based on imaging parameters may also appear in a healthy population.

A meta-analysis including 2501 LVNC patients revealed a risk of cardiovascular mortality similar to that of DCM patients, with no relation to the extent of trabeculation. CMR-based detection of focal fibrosis using LGE in LVNC with preserved ejection was associated with serious cardiac events (aborted death, ICD therapy, heart transplantation [HTX]/LVAD) in another meta-analysis including 574 patients (OR 6.1; CI 2.1–17.5; P, 0.001). A combination of CMR criteria with systematic genotyping may overcome current uncertainties regarding risk stratification.

Recommendation Table 31 — Recommendations for implantable cardioverter defibrillator implantation in left ventricular non-compaction

Recommendations	Classa	Levelb	© ESC 2022
In patients with a LVNC cardiomyopathy phenotype based on CMR or echocardiography, implantation of an ICD for primary prevention of SCD should be considered to follow DCM/ HNDCM recommendations.	IIa	C

CMR, cardiac magnetic resonance; DCM, dilated cardiomyopathy; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; LVNC, left ventricular non-compaction; SCD, sudden cardiac death. aClass of recommendation. bLevel of evidence.

7.1.3.5. Restrictive cardiomyopathy

The phenotype of restrictive cardiomyopathy (RCM) is rare and can be the consequence of different aetiologies, including infiltrative disorders (e.g. amyloidosis) and storage disease (e.g. Andersen–Fabry disease), the identification of which is crucial for guiding therapy.

Heart failure is one of the leading symptoms in primary and secondary RCM.

In Fabry disease the majority of the reported cardiovascular deaths have been categorized as SCD in a recent systematic review of 13 studies including 4185 patients. Higher age, male gender, LVH, LGE, and NSVT have been identified as potential risk factors associated with SCD events. However, SCD rates were reported in only 11 of the studies, including 623 patients. The retrospective, observational nature of most of these small, single-centre studies and the low absolute number of cardiovascular deaths (36/623) and SCD (30/623) do not currently allow guidance for primary prevention ICD implantation.

Amyloidosis can be caused by different misfolded precursor proteins leading to deposits in tissue and organs. Cardiac amyloidosis is mainly related to light-chain amyloid or transthyretin amyloid. The latter can be subdivided into wild-type, also called senile amyloid, more often complicated by AV conduction delay and atrial arrhythmias, and amyloid due to pathogenic mutations in the TTR gene. Disease manifestation depends on the mutation. Despite advances in the treatment of amyloid light-chain amyloidosis, outcome is still poor in patients with manifest cardiac involvement. Causes of death are progressive heart failure, autonomic dysfunction, and electromechanical dissociation. The benefit of primary prevention ICD implantation in patients with cardiac amyloidosis is uncertain. Currently, an ICD should be considered in patients with haemodynamically not-tolerated VT after careful discussion of the competing risks of non-arrhythmic death and non-cardiac death.

Recommendation Table 32 — Recommendations for implantable cardioverter defibrillator implantation in patients with cardiac amyloidosis

Recommendations	Classa	Levelb	© ESC 2022
An ICD should be considered in patients with light-chain amyloidosis or transthyretin-associated cardiac amyloidosis and haemodynamically not-tolerated VT.	IIa	C

ICD, implantable cardioverter defibrillator; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

7.1.3.6. Neuromuscular disorders

An algorithm for risk stratification, SCD prevention, and treatment of VAs in myotonic dystrophy is presented in Figure 23.

Arrhythmias are common and often the first manifestation of neuromuscular disorders. Myotonic dystrophy is the most common muscular dystrophy in the adult population (prevalence 1 in 8000). Myotonic dystrophy is the consequence of trinucleotide repeat expansion in the end of DMPK gene, which results in mis-splicing of SCN5A and cardiac conduction system delays and arrhythmia. Duchenne dystrophy also has a high incidence (1 in 3500 male births). As most patients die before the age of 20, it is rarely seen in adulthood. Other neuromuscular disorders, such as Becker (1 in 100000 male births) and facioscapulohumeral (1 in 100000) dystrophies, are less common. Most of these disorders are associated with conduction and rhythm

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----- Start of picture text ----- Patient with myotonic dystrophy Syncope or Aborted Asymptomatic palpitationsa cardiac arrest VT Pacema k er/ICDc Spontaneous A V blockb Y implantation Y Spontaneous A V blockb N EP(Class I)evaluation (Class I) N PR ≥240 ms or EP evaluationd QRS >120 ms or (Class IIa) >40 y and atrialarrhythmias or Y Pacema k er/ICDc >40 y and LGE implantation on CMR (Class IIb) N Y Follow-up PR/QRS (Class I) sudden increase N Asymptomatic/palpitations HV ≥70 ms BBR-VT Aboarrest/VT andrted cardiac Syncopea or and negative or subnodal A V block non-BBR VT or and non-BBRpalpitationsVT EP evaluation no VT induction Catheter ablation (Class I) Pacema k er/ICDc Follow-up ICD implantation ICD implantation implantation (Class I) (Class I) (Class IIa) (Class I) ----- End of picture text -----

Figure 23 Algorithm for risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmia in myotonic dystrophy. AV, atrioventricular; BBR-VT, bundle branch re-entrant ventricular tachycardia; CMR, cardiac magnetic resonance; EP, invasive electrophysiological evaluation; HV, His-to-ventricle interval; ICD, implantable cardioverter defibrillation; LGE, late gadolinium enhancement; N, No; VT, ventricular tachycardia, Y, Yes.[a] Syncope or palpitations highly suspicious of arrhythmic origin.[b] Spontaneous AV block: third or advanced second-degree AV block.[c] Factors favouring ICD implantation: age, CTG expansion, sudden death (SD) orfamily history of SD, ECG conduction abnormalities, PRprolongation, left bundle branch block, atrial arrhythmias, non-sustained VT, LV dysfunction, significant LGE in CMR.[d] Further management according to outcome of EP evaluation.

disturbances, some life-threatening, and with mechanisms amenable to specific anti-arrhythmic therapy. Anti-arrhythmic therapy should be considered, as muscular function and life expectancy are often only moderately limited. It is generally recommended to treat patients with neuromuscular diseases who have survived a CA or have VAs or ventricular dysfunction in the same way as patients without extracardiac manifestations. However, the benefit of ICD implantation should be balanced with the overall prognosis in some subtypes, such as Duchenne dystrophy.

Symptoms may be the result of bradycardia or tachyarrhythmias and invasive electrophysiological evaluation is warranted

unless a cause, such as AV block, has been clinically documented. Sudden increase of PR interval and QRS duration have been associated with AV block and SCD in myotonic dystrophy despite the absence of symptoms, and electrophysiological evaluation should be considered. An HV interval ≥70 ms should prompt pacemaker implantation regardless of symptoms. Induction of BBR-VT in a symptomatic patient strongly supports BBR-VT ( ESC CardioMed chapter 42.5) as an underlying cause of symptoms, and ablation of the right bundle branch is recommended. Following bundle branch ablation, the risk of AV block at follow-up is considered particularly high due to

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progressive His–Purkinje disease, and a pacemaker should be implanted. Prolonged PR or QRS intervals, concurrent atrial arrhythmias, and LGE at CMR in patients older than 40 years have all been associated with AV block and SCD at follow-up in myotonic dystrophy. Accordingly, pacemaker implantation may be considered even in the absence of symptoms. Although data are lacking, implantation of an ICD rather than a pacemaker may be preferred in myotonic dystrophy patients, with additional risk factors for VA and SCD (Figure 23). Permanent pacemaker implantation may also be considered in patients with Kearns–Sayre syndrome, Emery–Dreiffus, or limb–girdle muscular dystrophy with any degree of AV block because of the substantial risk of rapid progression to total block. In patients with limb–girdle type 1B or Emery–Dreifuss muscular dystrophies who have an indication for pacing or significant LGE on CMR, ICD implantation should be considered.

Implantation of an ICD rather than a pacemaker may be also considered in patients with Duchenne/Becker, when there is significant LGE on CMR. However, the general prognosis of these diseases should be taken into consideration. In patients who have survived a CA due to a SMVT, implantation of an ICD is recommended when other than BBR-VTs (e.g. scar-related VTs) are inducible or if VT is not inducible. Myotonic dystrophy patients with a syncope likely due to a VA, even if not inducible, and those with palpitations and induction of a non-BBR-VT are considered at risk for arrhythmic SCD, and ICDs should be considered.

Due to the progressive nature, annual follow-up with an ECG is recommended, even in the concealed phase of the disease when patients are asymptomatic and the ECG is normal. Due to slow progression and the fact that significant changes are often reflected on the surface ECG, serial electrophysiological evaluation to assess AV conduction and arrhythmia induction is not recommended in patients without arrhythmia suspicion or progression of ECG conduction disorders.

Recommendation Table 33 — Recommendations for risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmias in neuromuscular diseases

Recommendations	Classa	Levelb
General recommendations
Annual follow-up with at least a 12-lead ECG is recommended in patients with muscular dystrophies, even in the concealed phase of the disease.6,13	I	C
It is recommended that patients with neuromuscular disorders who have VAs or ventricular dysfunction are treated in the same way for arrhythmia as patients without neuromuscular disorders.17,765	I	C
Risk stratifcation, primary and secondary prevention of SCD
Invasive electrophysiological evaluation is recommended in patients with myotonic dystrophy and palpitations or syncope suggestive of VA or survivinga CA.153	I	C

ICD implantation is recommended in patients with myotonic dystrophy and SMVT or aborted CA not caused by BBR-VT.766	I	C
Invasive electrophysiological evaluation should be considered in patients with myotonic dystrophy and a sudden increase in the PR interval or QRS duration.766,767	IIa	B
Invasive electrophysiological evaluation should be considered in patients with myotonic dystrophy and a PR interval≥240 ms or QRS duration ≥120 ms or who are older than 40 years and have supraventricular arrhythmiasc or who are older than 40 years and have signifcant LGE on CMR.c,5,14,16,766	IIa	B
In myotonic dystrophy patients without AV conduction delay and a syncope highly suspicious for VA, ICD implantation should be considered.766	IIa	C
In myotonic dystrophy patients with palpitations highly suspicious for VA and induction of a non-BBR-VT, ICD implantation should be considered.766	IIa	C
In patients with limb–girdle type 1B or Emery– Dreifuss muscular dystrophies and indication for pacing, ICD implantation should be considered.769	IIa	C
Implantation of an ICD may be considered in patients with Duchenne/Becker muscular dystrophy and signifcant LGE at CMR.770,771	IIb	C
Implantation of an ICD over a permanent pacemaker may be considered in myotonic dystrophy patients with additional risk factorsd for VAs and SCD.	IIb	C
In myotonic dystrophy patients, serial electrophysiological evaluation of AV conduction and arrhythmia induction is not recommended without arrhythmia suspicion or progression of ECG conduction disorders.772	III	C
Management of VA
In symptomatic patients with BBR-VT, catheter ablation is recommended.e,153,474,475,477	I	C
In patients with myotonic dystrophy undergoing ablation for BBR-VT, pacemaker/ICD implantation is recommended.153	I	C

AV, atrioventricular; BBR-VT, bundle branch re-entrant ventricular tachycardia; CA, cardiac arrest; CMR, cardiac magnetic resonance; ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; LBBB, left bundle branch block; LGE, late gadolinium enhancement; LV, left ventricular; SCD, sudden cardiac death; SD, sudden death; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cLevel of evidence C. dFactors favouring ICD implantation: Age,5,6,11 CTG expansion,6–9,13,16 SD or family history of SD, ECG conduction abnormalities, PR prolongation, LBBB, atrial arrhythmias, non-sustained VT, LV dysfunction, structural abnormalities in CMR. eIn other cardiac conditions (e.g. aortic valve replacement) with BBR-VT, catheter ablation is also recommended.

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7.1.4. Inflammatory cardiac diseases

Cardiac inflammation has been associated with altered myocardial electrical properties and arrhythmias, and has been reported in various cardiomyopathies such as, obviously, myocarditis, but also inherited cardiomyopathies or after MI.

Inflammatory cardiomyopathies are characterized by myocardial inflammation (i.e. myocarditis) as the primary cause of cardiac damage, whereas secondary myocardial inflammations are caused by an initial myocardial pathology.

Myocarditis, sarcoidosis, and Chagas’ disease are among the major entities within inflammatory cardiomyopathies.

7.1.4.1. Myocarditis

The diagnosis of myocarditis can be challenging. There is no pathognomonic clinical presentation of this disease, with cardiac manifestations ranging from subtle symptoms to severe heart failure, complete AV block, and SCD. In young people, it is estimated that 2–12% of SCD are related to myocarditis.

Myocarditis is diagnosed on endomyocardial biopsy by established histological, immunological, and immunohistochemical criteria, as well as polymerase chain reaction (PCR) to detect viral genomes. This implies that endomyocardial biopsy, although not widely used, is the diagnostic gold standard for myocarditis. In current practice, the diagnosis of myocarditis relies on clinical presentation, elevated troponin level, ECG changes, evidence of LV dysfunction, absence of significant CAD or valvular heart disease, and suggestive findings on CMR or PET-CT.

In the context of suspected or confirmed acute myocarditis, patients with a life-threatening presentation (fulminant myocarditis, sustained VAs, or complete AV block) are to be referred to a specialized centre. A specialized centre must have the capacity to perform cardiac catheterization, endomyocardial biopsies, use mechanical circulatory support devices, and manage complex VAs.

Sustained VAs may occur in acute myocarditis. In a large series of patients, in-hospital VF or CA was reported in 2.5% of cases. In another series of acute myocarditis in children, sustained tachyarrhythmias were reported in 11.5% of patients, with VAs accounting for most cases (79.5%). Tachyarrhythmias were associated with a 2.3-fold increased risk of death. Giant cell myocarditis, although rare, has a higher risk of life-threatening VAs, which are seen in 14% of giant cell myocarditis patients on initial presentation, and then develop as refractory arrhythmias in more than half of the patients during the course of the disease.

The management of acute myocarditis depends on clinical presentation, viral PCR from myocardial biopsies, and histological findings. In patients with suspected myocarditis who present with mild heart failure, it is recommended to avoid exercise and use beta-blockers and ACE inhibitors. Patients with VAs or AV block must be admitted to the hospital and continuously monitored.

Treatment of arrhythmias in patients with inflammatory heart disease does not differ from generally accepted clinical principles. Symptomatic VAs may require AADs such as amiodarone and/or beta-blockers. Of note, in a retrospective observational study, patients with sustained VAs during the acute phase of myocarditis (LVEF 53 + 10%) had a high risk (45% at 3 years) of VT/VF recurrences during follow-up.

Myocarditis may resolve without sequelae, recur, or become chronic. Thus, myocarditis is often considered a precursor of

DCM. Development of DCM has been observed in 21% of patients with acute myocarditis over a mean follow-up period of 3 years. The exact proportion of chronic DCM consecutive to the progression of acute myocarditis remains unknown, but myocarditis has been identified as the cause of DCM in up to 12% of cases in a large retrospective study. In patients with SMVT of unclear aetiology, myocarditis should be suspected especially when CMR reveals subepicardial and/or intramural abnormal fibrotic myocardial tissue. The presence of LGE at CMR has also been associated with the late occurrence of VAs in patients with endomyocardial biopsy-proven viral myocarditis.

The management of documented VAs in chronic myocarditis is similar to that of patients with DCM, including ICD implantation and the use of AADs. Catheter ablation can be effective to treat SMVT, the arrhythmogenic substrate of which is often found on the epicardium of the lateral/basal left ventricle. In one publication, non-inducibility of VT after catheter ablation led to avoidance of ICD implantation in one-third of patients, with subsequently no VT recurrence during follow-up.

Recommendation Table 34 — Recommendations for sudden cardiac death prevention and treatment of ventricular arrhythmias in myocarditis

Recommendations	Classa	Levelb
General recommendations
In confrmed or clinically suspected acute myocarditis, it is recommended that patients who present with life-threatening VAs are referred to a specialized centre.786,804	I	C
Secondary prevention of SCD and treatment of VA
In patients with haemodynamically not-tolerated SMVT occurring in the chronic phase of myocarditis, an ICD implantation is recommended.794,805	I	C
In patients with haemodynamically not-tolerated sustained VT or VF during the acute phase of myocarditis, ICD implantation before hospital discharge should be considered.788,794,806	IIa	C
AADs should be considered (preferably amiodarone and beta-blockers) in patients with symptomatic non-sustained or sustained VAs during the acute phase of myocarditis.	IIa	C
In post-myocarditis patients with recurrent, symptomatic VT, AAD treatment should be considered.	IIa	C
Catheter ablation, performed in specialized centres, should be considered in post-myocarditis patients with recurrent, symptomatic SMVT or ICD shocks for SMVT in whom AADs are ineffective, not tolerated, or not desired.752,801,802	IIa	C
In patients with haemodynamically tolerated SMVT occurring in the chronic phase of myocarditis, ICD implantation should be considered.	IIa	C

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In patients with haemodynamically well-tolerated SMVT occurring in the chronic phase of myocarditis, preserved LV function and a limited scar amenable to ablation, catheter ablation may be considered as an alternative to ICD therapy, after discussion with the patient and provided that established endpoints have been reached.c	IIb	C © ESC 2022

AAD, anti-arrhythmic drug; ICD, implantable cardioverter defibrillator; LV, left ventricular; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cVT non-inducibility and elimination of electrograms consistent with conduction delay.

7.1.4.2. Cardiac sarcoidosis

Sarcoidosis is a multisystem inflammatory disease of unknown cause, with a genetic predisposition, characterized by the accumulation of T lymphocytes, mononuclear phagocytes, and non-caseating granulomas leading to tissue scarring. Although lung involvement is most frequent, any organ can be affected. It is estimated that 5% of patients with sarcoidosis have symptoms indicative of cardiac involvement. However, using advanced cardiac imaging modalities (CMR/PET-CT), subclinical cardiac sarcoidosis is increasingly diagnosed.

The diagnosis of cardiac sarcoidosis is challenging. It can mimic the ARVC phenotype in the event of a predominant RV involvement or the heart is the only organ affected by sarcoidosis (so-called ‘isolated cardiac sarcoidosis’). Cardiac electroanatomical voltage mapping may help in the differential diagnosis between isolated cardiac sarcoidosis and ARVC. The three usual cardiac manifestations of cardiac sarcoidosis are LV dysfunction, AV conduction abnormalities, and VAs. Complete AV block develops primarily during the acute inflammatory phase as opposed to sustained VT, which frequently develops in the advanced stage of the disease (Figure 24).

In addition to isolated cardiac sarcoidosis, three independent factors have been found associated with an adverse outcome and, particularly, the risk of VAs: (i) an LVEF,35%; (ii) documentation of high-degree AV block; and (iii) presence of RV or LV scarring at CMR (Figure 25). However, VAs and SCD may occur in patients with a mildly reduced or normal LVEF. PES, PET-CT, and LGE-CMR help stratify the risk of VAs in such patients. In a series of 120 patients with biopsy-proven extracardiac sarcoidosis and preserved LV/RV systolic function, VT inducibility at PES was low (6%) but associated with the composite endpoint of VAs and SCD, which occurred in 3 patients, all with abnormal PET or CMR (P = 0.009). In a cohort of 66 asymptomatic patients with biopsyproven extracardiac sarcoidosis and abnormal PET-CT or CMR, 8 (11%) were inducible at PES and 6 of 8 had VA or died during followup, compared to 1 of 68 non-inducible patients (P, 0.0001). Of note, inducible patients had a lower LVEF at PES, which further deteriorated at 2-year follow-up.

The benefit of ICDs, both for primary and secondary prevention, has been reported. Data support the use of ICDs for primary prevention of SCD in patients with LVEF ≤35%. In addition,

whatever the LVEF, ICD should also be considered in patients with anindication for permanent cardiacpacingor the presence of significant scaratCMR. Indeed,asshownintworecent meta-analyses, the occurrence of VA is higher in patients with complete AV block (OR = 2.19; P, 0.01), and the presence of scar at CMR is associated with a higher risk of the composite endpoint of ventricular arrhythmic events and mortality (OR = 10.74; P, 0.00001). A widely accepted definition of significant LGE is not available. LGE in ≥9/29 segments (17 LV and 12 RV segments) and LGE affecting ≥22% of the LV mass have been associated with arrhythmic endpoints.

Corticosteroid therapy is a mainstay of cardiac sarcoidosis treatment, but the effect of this treatment on the occurrence of VAs has only been ascertained from observational studies. Obviously, based upon pathophysiology of the disease, inflammation plays a role in the development of ventricular scar in patients with cardiac sarcoidosis. However, so far there is no evidence that VAs are directly triggered by active inflammation itself. Indeed, a scar-related intramural or epicardial substrate (with a predilection in peri-valvular regions) explains most VTs in patients with cardiac sarcoidosis. The VT substrate was more likely located in segments with scar transmurality at CMR and a lower degree of inflammation on PET-scan. Catheter ablation may help to prevent VT, in particular if AAD treatment fails, but VT recurrences are still frequent, in particular if catheter ablation is performed during active inflammation, with AADs continued in many patients.

Recommendation Table 35 — Recommendations for risk stratification, sudden cardiac death prevention, and treatment of ventricular arrhythmias in cardiac sarcoidosis

Recommendations	Classa	Levelb
Risk stratifcation and primary prevention of SCD
ICD implantation is recommended in patients with cardiac sarcoidosis who have a LVEF ≤35%.812,828–830,832	I	B
In patients with cardiac sarcoidosis who have an indication for permanent cardiac pacing related to high-degree AV block, ICD implantation should be considered, regardless of LVEF.816	IIa	C
In patients with cardiac sarcoidosis who have a LVEF.35% but signifcant LGE at CMR after resolution of acute infammation, ICD implantation should be considered.817–819,821,833,834	IIa	B
In patients with cardiac sarcoidosis who have a LVEF 35–50% and minor LGE at CMR, after resolution of acute infammation, PES for risk stratifcation should be considered.	IIa	C
In patients with cardiac sarcoidosis, LVEF 35–50% and inducible SMVT at PES, ICD implantation should be considered.823–825	IIa	C

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----- Start of picture text ----- Secondary prevention of SCD and treatment of VAs ICD implantation is recommended in patients with cardiac sarcoidosis who (1) have I B documented sustained VT, or (2) aborted CA. In patients with cardiac sarcoidosis and recurrent, symptomatic VA, AAD treatment should be IIa C considered. Catheter ablation, in specialized centres, may be considered in cardiac sarcoidosis ICD-recipients with recurrent, symptomatic SMVT or ICD IIb C shocks for SMVT, in whom AADs are ineffective, contraindicated, or not tolerated. 2022 ESC © ----- End of picture text -----

AAD, anti-arrhythmic drug; AV, atrio-ventricular; CA, cardiac arrest; CMR, cardiac magnetic resonance; ICD, implantable cardioverter defibrillator; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; PES, programmed electrical stimulation; SCD, sudden cardiac death; SMVT, sustained monomorphic VT; AV, ventricular arrhythmia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

7.1.4.3. Chagas’ cardiomyopathy

Chagas’ disease, a myocardial disease caused by the parasite Trypanosoma cruzi, is the most common cause of non-ischaemic cardiomyopathy in Latin America. After the incubation period, the vast majority of infected persons have minor or no symptoms, and very few (,1%) develop acute myocarditis. However, people are infected for life, and years to decades after the initial infection 20– 30% of them will develop cardiomyopathy, which can lead to heart failure, heart block and atrial and ventricular arrhythmias. SCD, particularly due to VF, is the most common cause of death in patients with Chagas’ cardiomyopathy. A risk score developed by Rassi et al. as well as the presence of myocardial fibrosis at LGE-CMR are useful in assessing the risk of death in Chagas’ disease patients. However, whether such risk stratification can translate into clinical benefit through ICD treatment needs to be assessed in prospective trials, also considering the high annual mortality in Chagas patients with ICDs.

Although ICD implantation may seem reasonable for the secondary prevention of SCD in patients with Chagas’ cardiomyopathy, there are controversial studies about the benefits and risks

----- Start of picture text ----- Patients with cardiac sarcoidosis Aborted cardiac arrest or Y ICD implantation sustained VT or L VEF ≤35% (Class I) N Indication f or permanent Y cardiac pacing N Significant LGEa Y N L VEF 35-50% N and minor LGE Y PES (Class IIa) Follow-up N SMVT inducible Y ICD implantation(Class IIa) Amiodarone (Class IIa) Symptomatic recurrent V A Catheter ablation (Class IIb) ----- End of picture text -----

Figure 24 Algorithm for sudden cardiac death prevention and treatment of ventricular arrhythmia in patients with cardiac sarcoidosis. ICD, implantable cardioverter defibrillator; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; N, No; PES, programmed electrical stimulation; SMVT, sustained monomorphic ventricular tachycardia; VA, ventricular arrhythmia; VT, ventricular tachycardia; Y, Yes.[a] LGE affecting ≥9/22 segments or ≥22% of the LV mass has been associated with arrhythmic endpoints.

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----- Start of picture text ----- ECG sinus rhythm – Prominent R’wave inV1-V3 [a] I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 ECG VT – LBBB-like, inferior axis (RVOT origin) I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 CMR PET-CT Basal LV and RV free wall LGE Lateral and basal-septal LV increased FDG uptake ----- End of picture text -----

Figure 25 Typical features of cardiac sarcoidosis associated with sustained monomorphic ventricular tachycardia. CMR, cardiac magnetic resonance; ECG, electrocardiogram; LBBB, left bundle branch block; LGE, late gadolinium enhancement; LV, left ventricle; PET-CT, positron emission tomography CT; RV, right ventricle; RVOT, right ventricular outflow tract; VT, ventricular tachycardia.[a] Note the prominent R[′] in V1 to V3, a pattern frequently found in cardiac sarcoidosis with RV involvement.

of ICD implantation in these patients. Indeed, a meta-analysis of observational studies found no benefit of ICD (n = 483) vs. amiodarone (n = 115) for the secondary prevention of SCD in patients with Chagas’ disease as all-cause annual mortality rates were comparable in both groups (9.7% and 9.6%, respectively). Another meta-analysis found a 4.7% annual incidence of inappropriate shocks

and a high 9.0% annual mortality rate in 1041 ICD patients with Chagas’ disease.

Amiodarone and catheter ablation have been successfully used to control recurrent VAs in some patients. As with various forms of myocarditis, the arrhythmogenic substrate is often found at the epicardium in Chagas’ cardiomyopathy.

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Recommendation Table 36 — Recommendations for the treatment of ventricular arrhythmias in Chagas’ cardiomyopathy

Recommendations	Classa	Levelb	© ESC 2022
Amiodarone should be considered to reduce arrhythmia burden in patients with Chagas’ cardiomyopathy who present with symptomatic PVCs or VT.857	IIa	C
In patients with Chagas’cardiomyopathy and recurrent, symptomatic SMVT or ICD shocks for SMVT in whom AADs are ineffective, contraindicated, or not tolerated, catheter ablation in specialized centres should be considered.859,860	IIa	C
In patients with Chagas’cardiomyopathy and symptomatic VT in whom AADs (amiodarone and beta-blockers) are ineffective or not tolerated, ICD implantation may be considered.851,854–856	IIb	C

AAD, anti-arrhythmic drug; ICD, implantable cardioverter defibrillator; PVCs, premature ventricular complexes; SMVT, sustained monomorphic ventricular tachycardia; VT, ventricular tachycardia.

7.1.5. Valvular heart disease

Valvular heart diseases predispose to SCD both in the preoperative period and after valvular surgery. In old cohorts of symptomatic, non-operated patients with severe aortic stenosis or severe mitral regurgitation, the incidence of SCD was 50–60%. In these studies, the rate of SCD secondary to VA was not specified.

Rates of SCD in patients with prosthetic valves range from 15% to 30%, with an estimated annual risk of 0.2–0.9%. In a large series of 1533 patients who underwent aortic or mitral valve replacement, 6% of deaths were caused by arrhythmias. A recent report of 3726 patients undergoing transcatheter aortic valve implantation (TAVI) showed 5.6% SCD during 22 months of followup, emphasizing the remaining SCD risk also after valve replacement.

Small observational studies have shown that patients with residual LV dysfunction after valvular surgery who undergo ICD implantation have appropriate therapy and mortality rates similar to patients with ischaemic or dilated cardiomyopathy. ICD implantation in these patients should therefore follow DCM/HNDCM recommendations.

In patients after TAVI, SCD has been associated with the presence of new-onset conduction disturbances (LBBB, QRS. 160 ms) and reduced LVEF ≤40%. SCD in these patients may be the consequence of advanced AV block, and permanent pacing indication should follow the 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. The role of ICD implantation for prevention of SCD after TAVI is less clear. Two recent retrospective analyses including a total of 203 patients in whom

the LVEF remained ≤35% did not show survival benefit from ICD implantation, probably related to the high competing risk of death from heart failure and relevant comorbidities in this population.

In patients presenting with SMVT after aortic valve replacement, PES is indicated because of the high probability of BBR-VT as the underlying mechanism—an arrhythmia that is potentially curable with catheter ablation.

– SCD has been reported to occur in 0.2 0.4% of patients with MVP per year. However, the total number of patients dying suddenly with this condition is most likely underestimated, considering that it is a common valve variant with an estimated prevalence of 2–3% in the general population.

Using rigorous criteria for morphologic diagnosis (i.e. myxomatous mitral valve) at post-mortem, MVP has been associated with 7% of all cases of juvenile SCD in the Registry of the Veneto region of Italy. Recent pathological and clinical studies on SCD victims with MVP or patients with MVP and major VAs have provided insights into the potential VA substrate. In particular, myocardial fibrosis affecting both the infero-basal LV free wall and the papillary muscles has been recognized in pathological and LGE-CMR studies. The scarring process has been related to mechanical stretch secondary to the excessive mobility of the mitral valve apparatus due to mitral valvular disjunction and posterior systolic curling. This indicates a promising role of CMR for arrhythmic risk stratification beyond traditional electrophysiological markers.

Proposed criteria for an ‘arrhythmic MVP syndrome’ that have been associated with an increased risk for SCD include: young adults (most often women), QTc prolongation and/or negative T-wave in inferior ECG leads, mitral annular disjunction, bi-leaflet involvement on echocardiography, frequent PVCs, or nonsustained PVT on Holter monitoring and/or exercise testing. Reduced LVEF and/or myocardial fibrosis on CMR may add to the risk profile. These data are mainly derived from small retrospective series of SCD survivors and post-mortem studies. Therefore, identification of the small subgroup of patients at risk of SCD remains challenging. Robust data to support recommendations for risk stratification of SCD in patients with MVP are not available.

Recommendation Table 37 — Recommendations for sudden cardiac death prevention and treatment of ventricular arrhythmias in valvular heart disease

Recommendations	Classa	Levelb
PES with standby catheter ablation is recommended in patients with aortic valve disease and SMVT to identify and ablate BBR-VT, especially if it occurs following a valve intervention.871,872,881	I	C
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In patients with valvular heart disease and persistent LV dysfunction after surgical correction, (if possible) it is recommended that I C ICD implantation for primary prevention follows DCM/HNDCM recommendations.

BBR-VT, bundle branch re-entrant ventricular tachycardia; DCM, dilated cardiomyopathy; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; LV, left ventricular; PES, programmed electrical stimulation; SMVT, sustained monomorphic ventricular tachycardia. aClass of recommendation. bLevel of evidence.

7.1.6. Congenital heart disease

Advances in surgical repair and medical treatment have improved the long-term prognosis of children born with congenital heart disease (CHD). More than 90% now survive to adulthood, and consequently the prevalence of adult CHD has steadily increased. With fewer patients dying from peri-operative events and early heart failure, SCD has become a leading cause of death in adults with repaired CHD. The

combination of surgical incisions, myocardial scar and residual or new anatomical abnormalities form the substrate for VAs (Figure 26).

Risk stratification for SCD in CHD patients and no documented sustained VA remains difficult due to a mixed patient population, the absence of RCTs, and relatively small observational studies. In patients with biventricular physiology and a systemic LV, the standard criterion of an LVEF ≤35% is used for patient selection for primary prevention ICD implantation. For patients with unexplained syncope, severe arrhythmia symptoms such as palpitations or presyncope and NSVT, PES should be considered. In asymptomatic patients with tetralogy of Fallot (TOF) but other indicators for a VA substrate, electrophysiological evaluation may refine risk stratification. The surgical era and the techniques used affect the VA substrate and occurrence of VAs and should be considered. The use of a transannular patch repair in TOF patients, for example, was found to be associated with a lower risk for VA. The benefit of primary prevention ICD therapy in patients with single or systemic RVs is less well established and requires consideration of disease- and patientspecific factors.

----- Start of picture text ----- Sustained VA in a patient with CHD Evaluation of residual or new anatomical abnormalities (Class I) Residual or new abnormalities Y requiring intervention Pre-operative catheter mapping and ablation before or during the intervention [a] (Class IIa) N Catheter or surgical intervention for correctable lesions ± ICD Simple or moderate CHD and preserved biventricular function and Y haemodynamically tolerated VT Catheter ablation [a] N (Class I) Recurrent symptomatic SMVT/ICD therapy despite ICD implantation N Successful ablation medical treatment [b] (Class I) Y Catheter ablation Withhold of ICD TOF Others implantation [a] (Class I) (Class IIa) (Class IIb) ----- End of picture text -----

Figure 26 Algorithm for the management of sustained ventricular arrhythmia in patients with congenital heart disease. CHD, congenital heart disease; ICD, implantable cardioverter defibrillator; N, No; TOF, tetralogy of Fallot; VA, ventricular arrhythmia; VT, ventricular tachycardia; Y, Yes.[a] Data derived from patients with TOF and related lesions.[b] In TOF, anti-arrhythmic drug failure is not required.

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In CHD patients with sustained VA or CA survivors, a comprehensive evaluation of inciting factors, including cardiac imaging (particularly CMR) and haemodynamic assessment, is important (Figure 26). If pre-existing or new anatomical abnormalities requiring intervention are detected, the treatment plan should consider pre- or intra-operative mapping and transection of the VT substrate, because accessibility might be impaired post-operatively. Pre-operative evaluation and intervention are especially important in TOF patients undergoing surgical pulmonary re-valving. In selected patients with CHD (including those with atrial baffle repair for transposition of the great arteries, Fontan operation and Ebstein anomaly), evaluation and treatment of SVT (such as intra-atrial re-entrant tachycardias or AV re-entrant tachycardias) with rapid ventricular conduction should also be considered.

In the absence of identifiable reversible factors, ICD implantation for secondary prevention of SCD is recommended. While transvenous ICD systems have been most frequently used and have the advantage of anti-tachycardia and anti-bradycardia pacing, subcutaneous ICDs may be an alternative in selected patients with limited venous access to the ventricle or with intracardiac shunts.

In CHD patients, MVT most often arises from re-entrant tachycardias using anatomical isthmuses bounded by valves, patch material, and surgical incisions. Early mapping and ablation studies, particularly in TOF patients, identified critical anatomical isthmuses of reproducible anatomical location. Following this concept, those anatomical isthmuses can be reconstructed and transected in sinus rhythm during catheter ablation procedures using electroanatomical mapping systems, achieving acute success rates of 80%. The use of conduction block across anatomical isthmuses as a procedural endpoint, in addition to non-inducibility of VT, has further improved long-term ablation outcomes. Accordingly, catheter ablation is recommended in particular in TOF patients with recurrent SMVT. Due to the complexity of CHD patients as well as the VT substrate, those procedures should be performed in centres with expertise in catheter ablation of CHD patients. Catheter ablation may be considered in lieu of ICD implantation in selected TOF patients with SMVT and preserved biventricular function, provided the combined procedural endpoint of non-inducibility and conduction block across the anatomical isthmus can be reached.

Recommendation Table 38 — Recommendations for risk stratification and primary prevention of sudden cardiac death in congenital heart disease

Recommendations	Classa	Levelb
Risk stratifcation and primary prevention of SCD
All CHD patients
In adults with CHD with biventricular physiology and a left systemic ventricle presenting with symptomatic heart failure (NYHA II/III) and EF ≤35% despite≥3 months of OMT, ICD implantation is indicated.885,886	I	C

In patients with CHD with presumed arrhythmic syncope and with either at least moderate ventricular dysfunction or inducible SMVT on PES, ICD implantation should be considered.887,889,902	IIa	C
In patients with advanced single ventricle or systemic RV dysfunction with additional risk factors,c ICD implantation may be considered.890,891	IIb	C
Tetralogy of Fallot
In patients after repair of TOF with arrhythmia symptoms and NSVT, electrophysiologic evaluation including PES should be considered.889,903–905	IIa	C
In patients after repair of TOF with arrhythmia symptoms and a positive PES, or a combination of other risk factorsd and a positive PES, ICD implantation should be considered.	IIa	C
In patients after repair of TOF without arrhythmia symptoms, but with a combination of other risk factors,d electrophysiologic evaluation, including PES, may be considered.	IIb	C
In patients with repaired TOF undergoing surgical or transcutaneous pulmonary valve replacement, pre-operative catheter mapping and transection of VT-related anatomical isthmuses before or during the intervention may be considered.894	IIb	C

AV, atrioventricular; CHD, congenital heart disease; CMR, cardiac magnetic resonance; EF, ejection fraction; ICD, implantable cardioverter defibrillator; LV, left valve; NSVT, non-sustained monomorphic ventricular tachycarda; NYHA, New York Heart Association; OMT, optimal medical treatment; PES, programmed electrical stimulation; RV, right ventricular; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycarda; TOF, tetralogy of Fallot; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cData are sparse and risk factors may be lesion-specific, including non-sustained VT, NYHA II/III, severe AV valve regurgitation, and wide QRS ≥140 ms (transposition of the great arteries). dOther risk factors include moderate RV or LV dysfunction, extensive RV scarring on CMR, QRS duration ≥180 ms and severe QRS fragmentation.

Recommendation Table 39 — Recommendations for secondary prevention of sudden cardiac death and treatment of ventricular arrhythmia in congenital heart disease

Recommendations	Classa	Levelb
Secondary prevention of SCD and treatment of VA
All CHD patients In patients with CHD presenting with sustained VAs, evaluation for residual lesions or new structural abnormalities is recommended.892,893 I		B
In patients with CHD with not tolerated VT/ aborted CA due to VF, ICD implantation is indicated after exclusion of reversible causes.349,350	I	C

Continued

Continued

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In patients with CHD and recurrent, symptomatic SMVT or ICD shocks for SMVT not manageable by medical therapy or ICD reprogramming, catheter ablation performed in specialized centres should be considered.c 899–901	IIa	C
In selected patients with CHD (including atrial baffe repair for transposition of the great arteries, Fontan operation and Ebstein anomaly) presenting with CA, evaluation and treatment of SVT with rapid ventricular conduction should be considered.890,895	IIa	C
Tetralogy of Fallot
In patients with repaired TOF who present with SMVT or recurrent, symptomatic appropriate ICD therapy for SMVT, catheter ablation performed in specialized centres is recommended.899–901	I	C
In patients with repaired TOF with SMVT who are undergoing surgical or transcutaneous pulmonary valve replacement, pre-operative catheter mapping and transection of VT-related anatomical isthmuses before or during the intervention should be considered.888,893,894	IIa	C
In patients with repaired TOF with a preserved biventricular function and symptomatic SMVT, catheter ablation or concomitant surgical ablation performed in specialized centres may be considered as an alternative to ICD therapy.899,901	IIb	C

CA, cardiac arrest; CHD, congenital heart disease; ICD, implantable cardioverter defibrillator; SCD, sudden cardiac death; SMVT, sustained monomorphic ventricular tachycardia; SVT, supraventricular tachycardia; TOF, tetralogy of Fallot; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cSpecific recommendations for TOF (Class I-B).

7.2. Primary electrical disease

7.2.1. Idiopathic ventricular fibrillation

The diagnosis of idiopathic ventricular fibrillation (IVF) is made in SCA survivors, preferably with documented VF, after exclusion of structural, channelopathic, metabolic, or toxicological aetiologies. Diagnostic tests include blood chemistry, ECG (including high lead), cardiac CT/coronary angiography, telemetry/ Holter, exercise stress test, echocardiogram, sodium-channel blocker testing and CMR (see Section 5.2.3, scenario 3). Genetic testing for channelopathy and cardiomyopathy genes may be considered with a mutation yield of 3–17%. Clinical evaluation of first-degree family members may be considered, but the diagnostic yield is low. In particular the significance of detected early repolarization pattern (ERP) in asymptomatic relatives is uncertain.

In IVF patients, ICD implantation reduces the risk of arrhythmic death by up to 68% compared to amiodarone (Figure 27). In observational studies with a mean follow-up of 5–6 – years, 21.0 29.6% of IVF patients experienced an arrhythmic recurrence, corresponding to an annual ICD shock rate of 3.6–5.7%, whereas 4.5–17.5% experienced inappropriate shocks.

Isoproterenol, verapamil, or quinidine have been employed for acute treatment of recurrent ICD discharges or electrical storm. In several small studies, quinidine was highly effective in reducing or even preventing arrhythmia inducibility during programmed stimulation. Moreover, a retrospective study in 46 patients showed a reduction of mean ICD shocks from 7.5 per patient over 2.9 years to 0.9 shocks per patient over 3.7 years, with a decrease in ventricular storms from 36 to 3 after quinidine initiation. In patients with recurrent episodes of VF triggered by a similar PVC unresponsive to medical treatment, catheter ablation has shown success (Figure 28). PVCs most commonly originate from the Purkinje system and can be eliminated with a high acute success rate of 87–100%. Detailed electroanatomic mapping may also reveal localized structural alterations (62.5% in one study).

Recommendation Table 40 — Recommendations for the management of patients with idiopathic ventricular fibrillation

Recommendations	Classa	Levelb
Diagnostic evaluation
It is recommended that idiopathic VF is diagnosed in a SCA survivor, preferably with documentation of VF, after exclusion of an underlying structural, channelopathic, metabolic, or toxicological aetiology.222,911	I	B
Clinical testing (history, ECG and high precordial lead ECG, exercise test, echocardiogram) of frst-degree family members of idiopathic VF patients may be considered.222,278,916	IIb	B
In idiopathic VF patients, genetic testing of genes related to channelopathy and cardiomyopathy may be considered.249,278,914,915	IIb	B
Secondary prevention of SCD and treatment of VA
ICD implantation is recommended in idiopathic VF.352,917–919	I	B
Isoproterenol infusion, verapamil, or quinidine for acute treatment of an electrical storm or recurrent ICD discharges should be considered in idiopathic VF.912,913,918,922–924,926	IIa	C
Quinidine should be considered for chronic therapy to suppress an electrical storm or recurrent ICD discharges in idiopathic VF.923,924	IIa	B
Catheter ablation by experienced electrophysiologists should be considered in idiopathic VF patients with recurrent episodes of VF triggered by a similar PVC non-responsive to medical treatment.927–930	IIa	C

ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; PVC, premature ventricular complex; SCA, sudden cardiac arrest; SCD, sudden cardiac death; VA, ventricular arrhythmia; VF, ventricular fibrillation. aClass of recommendation. bLevel of evidence.

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----- Start of picture text ----- Patient with idiopathic ventricular fibrillation ICD implantation (Class I) Genetic counselling and testing (Class IIb) Recurrent ICD shocks Acute treatment: Isoproterenol V erapamil Quinidine (Class IIa) Chronic treatment: Quinidine (Class IIa) Recurrent ICD shocks Catheter ablation of PVC triggers (Class IIa) ----- End of picture text -----

Figure 27 Algorithm for the management of patients with idiopathic ventricular fibrillation. ICD, implantable cardioverter defibrillator; PVC, premature ventricular complex.

7.2.2. Long QT syndrome (including acquired long QT syndrome)

LQTS is characterized by a prolonged QT interval and VAs mainly triggered by adrenergic activation. The mean age at presentation is 14 years. The annual rate of SCD in asymptomatic patients with untreated LQTS has been estimated to be less than 0.5%, while it increases to around 5% in those with history of syncope.

Rare variants in 17 genes have been associated with LQTS. However, the causality for several of the identified genes has been questioned. The undisputed genes are those causing LQT1, LQT2 and LQTS3: KCNQ1, KCNH2 and SCN5A, respectively, with genespecific triggers being exercise (LQTS1), emotional stress (LQTS2) and sleep (LQTS3). Genetic screening identifies a mutation in 75% of LQTS cases and three main genes account for 90% of positively genotyped cases. The subtypes of LQTS may be grouped as follows:

• (1) Autosomal-dominant LQTS (prevalence: 1 in 2500) without extra-cardiac manifestation.

• (2) Autosomal-dominant LQTS with extra-cardiac manifestation, comprising:

• (a) Andersen–Tawil Syndrome (LQT7), increasingly considered its own entity.

• (b) Timothy Syndrome (LQT8), characterized by prolonged QT, syndactyly, cardiac malformations, autism spectrum disorder and dysmorphism.

• (3) Autosomal-recessive LQTS (Jervell and Lange–Nielsen Syndrome), combining extreme QT prolongation with congenital deafness.

This panel of experts has confirmed the diagnostic criteria proposed in the previous version of the guidelines: a QTc ≥480 ms or a LQTS risk score.3 (Table 10) for clinical diagnosis (Figures 29 and 30). In the presence of arrhythmic syncope or CA, a QTc ≥460 ms is sufficient to consider a diagnosis of LQTS. A challenge for the clinician is establishing the duration of the QT interval in patients with broad QRS complexes (e.g. in the presence of ventricular pacing or ventricular conduction defects). In this setting, a formula has been proposed that adjusts QT by QRS duration. While measuring the QT, the patient moving briskly from recumbent to

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----- Start of picture text ----- ECG sinus rhythm – short-coupled PVCs Telemetry tracings – short-coupled PVC inducing VF ----- End of picture text -----

Figure 28 Idiopathic ventricular fibrillation triggered by short-coupled premature ventricular complexes. ECG, electrocardiogram; PVC, premature ventricular complex; VF, ventricular fibrillation.

orthostatic position may be helpful for the diagnosis of LQTS.

Epinephrine challenge is not recommended as a routine diagnostic tool, as reproducibility is modest. Patients with a clinical diagnosis of LQTS are recommended to undergo genetic counselling and testing in specialized centres to receive genotype-specific management and permit identification of relatives at risk. Relatives with a mutation but without QT prolongation still receive a diagnosis of LQTS, as they are at risk of experiencing VA, although less frequently than phenotype-positive patients.

All LQTS patients receive advice on avoidance of hypokalaemia, QT-prolonging medications and genotype-specific triggers. Beta-blockers are also recommended in all LQTS patients. Non-selective beta-blockers nadolol and propranolol

have greater efficacy in reducing arrhythmic risk. Clinical, electrocardiographic and genetic parameters should be considered for the individual risk estimation. Recently, risk stratification based on QT interval duration and genotype has been integrated in a LQTS calculator (the 1-2-3 LQTS Risk calculator).

The utility of genetic testing is exemplified by the need to avoid genotype-specific risks and by the use of mexiletine as a genotypespecific treatment for LQT3, which reduces the length of QT interval and the number of arrhythmic events. It should be noted that different mutations in SCN5A show different responses to mexiletine. For example, selected mutations identified in patients not responding to mexiletine showed a distinctive electrophysiological profile

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Table 10 Modified long QT syndrome diagnostic score

Findings	Findings	Findings	Points	© ESC 2022
ECG	QTc	≥480 ms	3.5
		=460–479 ms	2
		=450–459 ms (in males)	1
		≥480 ms during 4th minute of recovery from exercise stress test	1
	Torsade de pointes		2
	T wave alternans		1
	Notched T wave in 3 leads		1
	Low heart rate for age		0.5
Clinical history	Syncope	With stress	2
		Without stress	1
Family history	Family member(s) with defnite LQTS		1
	Unexplained SCD at age,30 years in frst-degree family		0.5
Geneticfnding	Pathogenic mutation		3.5

ECG, electrocardiogram; LQTS, long QT syndrome; SCD, sudden cardiac death. Diagnosis of LQTS with a score.3.

when studied in vitro. Additionally, in the case of mutations that cause overlapping syndromes, mexiletine does not induce ST segment elevation, while flecainide has been reported to do so.

Given the uncertain role of beta-blockers in LQT3, there are no indications on whether mexiletine should be administered as a stand-alone therapy or in combination with beta-blockers. Considering that some mutations may not respond to mexiletine, it is advisable to perform oral testing to verify that the QTc shortens 40 ms before prescribing chronic treatment.

Survivors of a CA have a high risk of recurrences, even on betablockers (14% within 5 years on therapy), supporting the use of ICD in CA survivors. Moreover, ICD implantation is indicated when a patient experiences syncope and/or VA despite optimal pharmacological therapy, as syncopal events are associated with increased risk of CA. Women with LQTS, particularly LQT2, have an increased risk of arrhythmia both during pregnancy and especially first year post-partum. Silent carriers of mutations present a low, but not negligible, risk of cardiac events, and the use of beta-blockers should be considered in this group of patients.

Left cardiac sympathetic denervation (LCSD) is recommended for symptomatic patients despite beta-blockers when ICD is contraindicated or declined, or for an ICD carrier who experiences multiple shocks while on beta-blockers. This is supported by the evidence that LCSD, especially when performed with a video-assisted technique, is safe and effective, well-tolerated by patients and does not have a negative impact on cardiovascular performance. However, because complications do occur and half of the patients experience breakthrough events after the procedure, LCSD is not an alternative to ICD for high-risk patients. Prophylactic ICD

----- Start of picture text ----- A LQT1 LQT2 LQT3 B I V1 II V2 III V3 aVR V4 aVL V5 aVF V6 ----- End of picture text -----

Figure 29 Long QT syndrome electrocardiograms and torsade-de-pointes ventricular tachycardia. (A) ECG characteristics in the three major LQTS phenotypes. (B) Example of Torsade-de-pointes in a male patient with a SCN5A (c.1238C.A, p.A413E) mutation. LQT, Long QT.

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----- Start of picture text ----- A Brisk Standing Test Recumbent Standing B T wave alternans I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 ----- End of picture text -----

Figure 30 Brisk standing electrocardiogram changes and T wave alternans in Long QT syndrome patients. (A) ECG changes during brisk standing test in a male LQTS patient with KCNH2 (p.S818L) mutation, increased heart rate is associated with less adaptation of QT interval. (B) T wave alternans in a male patient with CACNA1C (p.G406R) mutation.

therapy in addition to OMT may be considered in asymptomatic LQTS patients identified with high-risk according to the 1-2-3 LQTS Risk calculator. PES is not useful for risk stratification in LQTS.

LQTS patients identifed with high-risk according to the 1-2-3 LQTS Risk calculator.947 PES is not useful for risk stratifcation in LQTS.961 Figure 31illustrates the algorithm for the management of patients with long QT syndrome. Recommendation Table 41—Recommendations for the management of patients with long QT syndrome Recommendations Classa Levelb Diagnosis It is recommended that LQTS is diagnosed with either QTc≥480 ms in repeated 12-lead ECGs with or without symptoms or LQTS diagnostic score.3. I C In patients with clinically diagnosed LQTS, genetic testing and genetic counselling are recommended. I C It is recommended that LQTS is diagnosed in the presence of a pathogenic mutation, irrespective of the QT duration. I C The LQTS diagnosis should be considered in the presence of a QTc≥460 ms and,480 ms in repeated 12-lead ECGs in patients with an arrhythmic syncope in the absence of secondary causes for QTprolongation.952,962,963 IIa C	LQTS patients identifed with high-risk according to the 1-2-3 LQTS Risk calculator.947 PES is not useful for risk stratifcation in LQTS.961 Figure 31illustrates the algorithm for the management of patients with long QT syndrome. Recommendation Table 41—Recommendations for the management of patients with long QT syndrome Recommendations Classa Levelb Diagnosis It is recommended that LQTS is diagnosed with either QTc≥480 ms in repeated 12-lead ECGs with or without symptoms or LQTS diagnostic score.3. I C In patients with clinically diagnosed LQTS, genetic testing and genetic counselling are recommended. I C It is recommended that LQTS is diagnosed in the presence of a pathogenic mutation, irrespective of the QT duration. I C The LQTS diagnosis should be considered in the presence of a QTc≥460 ms and,480 ms in repeated 12-lead ECGs in patients with an arrhythmic syncope in the absence of secondary causes for QTprolongation.952,962,963 IIa C	LQTS patients identifed with high-risk according to the 1-2-3 LQTS Risk calculator.947 PES is not useful for risk stratifcation in LQTS.961 Figure 31illustrates the algorithm for the management of patients with long QT syndrome. Recommendation Table 41—Recommendations for the management of patients with long QT syndrome Recommendations Classa Levelb Diagnosis It is recommended that LQTS is diagnosed with either QTc≥480 ms in repeated 12-lead ECGs with or without symptoms or LQTS diagnostic score.3. I C In patients with clinically diagnosed LQTS, genetic testing and genetic counselling are recommended. I C It is recommended that LQTS is diagnosed in the presence of a pathogenic mutation, irrespective of the QT duration. I C The LQTS diagnosis should be considered in the presence of a QTc≥460 ms and,480 ms in repeated 12-lead ECGs in patients with an arrhythmic syncope in the absence of secondary causes for QTprolongation.952,962,963 IIa C	Routine diagnostic testing with epinephrine challenge is not recommended in LQTS.137	III	C
			General recommendations to prevent SCD
			The following is recommended in LQTS: • Avoid QT-prolonging drugs.c • Avoid and correct electrolyte abnormalities. • Avoid genotype-specifc triggers for arrhythmias.943	I	C
			Beta-blockers, ideally non-selective beta-blockers (nadolol or propranolol), are recommended in LQTS patients with documented QT interval prolongation, to reduce risk of arrhythmic events.940,945,946	I	B
Recommendations	Classa	Levelb
Diagnosis
It is recommended that LQTS is diagnosed with either QTc≥480 ms in repeated 12-lead ECGs with or without symptoms or LQTS diagnostic score.3.	I	C
			Mexiletine is indicated in LQT3 patients with a prolonged QT interval.948	I	C
			Beta-blockers should be considered in patients with a pathogenic mutation and a normal QTc interval.82	IIa	B
In patients with clinically diagnosed LQTS, genetic testing and genetic counselling are recommended.	I	C
It is recommended that LQTS is diagnosed in the presence of a pathogenic mutation, irrespective of the QT duration.	I	C	Risk stratifcation, prevention of SCD and treatment of VA
			ICD implantation in addition to beta-blockers is recommended in LQTS patients with CA.952,953,962,963	I	B
The LQTS diagnosis should be considered in the presence of a QTc≥460 ms and,480 ms in repeated 12-lead ECGs in patients with an arrhythmic syncope in the absence of secondary causes for QTprolongation.952,962,963	IIa	C
			ICD implantation is recommended in patients with LQTS who are symptomaticd while receiving beta-blockers andgenotype-specifc therapies.	I	C

Continued

Continued

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----- Start of picture text ----- LCSD is indicated in patients with symptomatic [d] LQTS when: (a) ICD therapy is contraindicated or declined; (b) patient is on beta-blockers and I C genotype-specific drugs with an ICD and experiences multiple shocks or syncope due to VA. Either ICD implantation or LCSD should be considered in patients with symptomatic [d] LQTS, when beta-blockers and genotype-specific IIa C therapies are not tolerated or contraindicated at the therapeutic dose. In LQTS, it should be considered to calculate the arrhythmic risk before initiation of therapy based on IIa C the genotype and the duration of QTc interval. Continued ----- End of picture text -----

----- Start of picture text ----- ICD implantation may be considered in asymptomatic LQTS patients with high-risk profile (according to the 1-2-3 LQTS Risk IIb B calculator) in addition to genotype-specific medical therapies (mexiletine in LQT3 patients). Invasive electrophysiologic study is not III C recommended in LQTS. 2022 ESC © ----- End of picture text -----

CA, cardiac arrest; ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; LCSD, left cardiac sympathetic denervation; LQTS, long QT syndrome; SCD, sudden cardiac death; VA, ventricular arrhythmia. aClass of recommendation. bLevel of evidence.

chttp://www.crediblemeds.org

dArrhythmic syncope or haemodynamically non-tolerated VA.

----- Start of picture text ----- Patient with long QT syndrome Asymptomatic patient Asymptomatic patient with Aborted cardiac arrest medical tSyncope prior toreatment with or without pathogenicmutation and pathogenic mutation QT prolongation without QT prolongation General recommendationsa (Class I) Beta-bloc k ersb (Class I) Beta-bloc k ersb (Class IIa) SCN5A mutation (LQT3): Mexiletine (Class I) If LQT1, LQT2 or LQT3, assess arrhythmic risk Arrhythmic syncope or Y non-tolerated V A with genotype and QTc (1-2-3-LQTS-Risk under medical thera p y riskcalculator) (Class IIb) N Medical thera p y High risk f eatures, N contraindicated, based on genotype N Follow-up or not tolerated and QTc Follow-up Y Y LCSD ICD implantation (Class IIb) (Class IIa) ICD implantation (Class IIa) ICD contraindicated, ICD implantation LCSD declined or (Class I) recurrent ICD shocks (Class I) ----- End of picture text -----

Figure 31 Algorithm for the management of patients with long QT syndrome. ICD, implantable cardioverter defibrillator; LCSD, left cardiac sympathetic denervation; LQT, long QT; N, No; VA, ventricular arrhythmia; Y, Yes.[a] General recommendations: avoidance of QT-prolonging drugs (http://www. crediblemeds.org), correction of electrolyte abnormalities (hypokalaemia, hypomagnesaemia, and hypocalcaemia), avoidance of genotype-specific triggers for arrhythmias (strenuous swimming in LQT1, exposure to loud noises in LQT2).[b] Preferred beta-blockers: nadolol and propranolol.

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7.2.3. Andersen–Tawil syndrome Type 1

Andersen–Tawil syndrome Type 1, also classified as LQT7, is a rare disease (1:1 000000) characterized by three main symptoms: frequent VA (e.g. bidirectional VT), dysmorphologies and periodic paralysis. The inward rectifier current (IK1) decreased by KCNJ2 loss of function mutation causes an increase in U wave amplitude rather than QT prolongation. Syncope or documented VT is associated with life-threatening VA, and a study found a 5-year probability of 7.9% of life-threatening VA. In patients with sustained haemodynamically not-tolerated VT or CA, an ICD is recommended. Flecainide and/or beta-blockers seem to reduce VA, whereas amiodarone may be proarrhythmic and should only be used with an ICD. In patients with syncope despite medical therapy, an ICD or ILR should be discussed.

Recommendation Table 42 — Recommendations for management of patients with Andersen–Tawil syndrome

Recommendations	Classa	Levelb
Diagnosis
Genetic testing is recommended in patients with	I	C
suspected Andersen–Tawil syndrome.964,967
Andersen–Tawil syndrome should be considered
in patients without SHD who present with at least
two of the following:
• Prominent U waves with or without
prolongation of the QT interval	IIa	C
• Bidirectional and/or polymorphic PVCs/VT
• Dysmorphic features
• Periodic paralysis
• KCNJ2pathogenic loss of function
mutation.964,965,967,968,972
Risk stratifcation, prevention of SCD and treatment of VA
ICD implantation is recommended in patients
with Andersen–Tawil syndrome after aborted CA	I	C
or not-tolerated sustained VT.964,967
Beta-blockers and/orfecainide with or without
acetazolamide should be considered in patients	IIa	C
with Andersen–Tawil syndrome to treat
VA.964,970
An ILR should be considered in patients with
Andersen–Tawil syndrome and unexplained	IIa	C
syncope.
ICD implantation may be considered in patients
with Andersen–Tawil syndrome who have a history of unexplained syncope or suffer from tolerated sustained VT.967	IIb	C	© ESC 2022

CA, cardiac arrest; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; PVCs, premature ventricular complexes; SCD, sudden cardiac death; SHD, structural heart disease; VA, ventricular arrhythmia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

7.2.4. Brugada syndrome

The type 1 Brugada ECG pattern is characterized by J point elevation of.2 mV with coved ST elevation and T wave inversion in at least one right precordial ECG lead, V1 or V2, positioned in the second, third or fourth intercostal spaces (Figure 32). It may occur either spontaneously or be induced by exposure to sodium channelblocking drugs or fever. It is mandatory to exclude other conditions that may explain the type 1 pattern, so-called phenocopies.

BrS is diagnosed in patients without other heart disease and a spontaneous type 1 pattern, regardless of symptoms, due to its rarity in the general population and association with risk. The type 1 pattern may also be induced by administration of a sodium channel-blocking drug as a diagnostic test in patients suspected to have concealed BrS but without a spontaneous type 1 ECG. However, provocation with drug or fever is less specific than previously thought, with 2–4% prevalence in healthy subjects and higher prevalence in patients with AV nodal reentry tachycardia or an accessory pathway in one study. In the opinion of this panel of experts, an induced type 1 ECG pattern therefore requires other clinical features, such as documented PVT/VF, arrhythmic syncope, or relevant family history.

The yield of genetic testing in BrS patients is approximately 20%, with the SCN5A gene the only gene with evidence of association for clinical testing purposes. Phenotype and genotype mismatch is seen in SCN5A families, which is explained by variable effects of mutation severity and a polygenic risk score derived from genome-wide association studies. Recent data also support a potential for prognostication.

Psychotropic drugs, selected AADs, anaesthetic agents, cocaine, excessive alcohol intake and fever are potential triggers to exacerbate the type 1 pattern and trigger VF. The risk of recurrent VF among patients presenting with CA is 48% at 10 years. ICD implantation is therefore indicated in symptomatic BrS patients who are survivors of CA or have documented spontaneous sustained VA (Figure 33). Approximately one-third of BrS patients present with syncope. The risk of arrhythmic events in BrS patients with unexplained syncope is 4 times higher than the risk in asymptomatic patients. Detailed patient history, including absence of prodrome or specific triggers, is essential for distinguishing arrhythmic from non-arrhythmic syncope. Nonetheless, the aetiology of syncope is difficult to determine in up to 30% of BrS patients. In small studies, arrhythmia detected by ILR changed – clinical management in 20 36% of the BrS patients with unexplained syncope.

Asymptomatic patients represent a majority of newly diagnosed BrS patients with an incidence of arrhythmic events of 0.5% per year. Their risk stratification remains challenging. A spontaneous type 1 ECG pattern, as well as other ECG markers such as early repolarization pattern and QRS fragmentation, have been associated with higher risk. Some have been incorporated into risk scores, although their utility in intermediate-risk patients remains low. Electrophysiological studies remain controversial. A multicentre pooled analysis showed that

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----- Start of picture text ----- A Brugada type 1 pattern ECG I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 B Early repolarization pattern ECG II III ----- End of picture text -----

Figure 32 Typical examples of (A) Brugada type 1 electrocardiogram, and (B) early repolarization pattern electrocardiogram. ECG, Electrocardiogram.

induction of sustained VA during electrophysiological studies was associated with a higher future risk of VA. Inducibility, however, was associated with a potentially clinically actionable result only in asymptomatic patients with a spontaneous type 1 Brugada pattern ECG.

In case of recurrent ICD shocks for VF, quinidine or catheter ablation have been successful in reducing shock frequency. Isoproterenol infusion can suppress electrical storm. In several small studies, quinidine was effective in reducing or even preventing arrhythmia inducibility during programmed stimulation. However, adverse effects of quinidine can occur in up to 37% of patients, and quinidine is inaccessible in many countries. Cilostazol (phosphodiesterase-3 inhibitor) can be an alternative to quinidine. Electrophysiological mapping data linked to histopathological studies suggest that an abnormal fibrotic arrhythmogenic substrate in the epicardial RVOT is responsible for the ST-segment elevation in the right precordial leads and VF occurrence in BrS patients. Ablation of these abnormal areas can markedly suppress recurrent VF and normalize the ECG in.75% of patients. In patients with recurrent episodes of VF triggered by a similar PVC non-responsive to medical treatment, catheter ablation may target the PVC, which most commonly originates from the RVOT or Purkinje system. However, data regarding the long-term follow-up after ablation are limited, with neither trial data nor evidence for ablation in asymptomatic patients.

Recommendation Table 43 — Recommendations for management of patients with Brugada syndrome

Recommendations	Classa	Levelb
Diagnosis
It is recommended that BrS is diagnosed in patients with no other heart disease and a spontaneous type 1 Brugada ECG pattern.974–976	I	C
It is recommended that BrS is diagnosed in patients with no other heart disease who have survived a CA due to VF or PVT and exhibit a type 1 Brugada ECG induced by sodium channel blocker challenge or during fever.135,136,975,981,982	I	C
Genetic testing forSCN5Agene is recommended for probands with BrS.164,1016	I	C
BrS should be considered in patients with no other heart disease and induced type 1 Brugada pattern who have at least one of: • Arrhythmic syncope or nocturnal agonal respiration • A family history of BrS • A family history of SD (,45 years old) with a negative autopsy and circumstance suspicious for BrS.	IIa	C
		Continued

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BrS may be considered as a diagnosis in
patients with no other heart disease who	IIb	C
exhibit an induced type 1 Brugada
ECG.136,973,975,978,984,985
Sodium channel blocker test is not
recommended in patients with a prior type I	III	C
Brugada pattern.
General recommendations
The following is recommended in all patients with
BrS:
(a) Avoidance of drugs that may induce
ST-segment elevation in right precordial	I	C
leads (http://www.brugadadrugs.org).
(b) Avoidance of cocaine, cannabis, and excessive
alcohol intake.
(c) Treatment of fever with antipyretic drugs.
Risk stratifcation, prevention of SCD and treatment of VA
ICD implantation is recommended in patients
with BrS who:
(a) Are survivors of an aborted CA and/or	I	C
(b) Have documented spontaneous sustained
VT.980,990–992
ICD implantation should be considered in patients
with type 1 Brugada pattern and an arrhythmic	IIa	C
syncope.990,992,996
Implantation of a loop recorder should be
considered in BrS patients with an unexplained	IIa	C
syncope.997,999
Quinidine should be considered in patients with
BrS who qualify for an ICD but have a	IIa	C
contraindication, decline, or have recurrent ICD
shocks.922,1006,1007
Isoproterenol infusion should be considered in	IIa	C
BrS patients suffering electrical storm.1008
Catheter ablation of triggering PVCs and/or
RVOT epicardial substrate should be considered	IIa	C
in BrS patients with recurrent appropriate ICD
shocks refractory to drug therapy.1010–1015
PES may be considered in asymptomatic patients	IIb	B
with a spontaneous type I BrS ECG.155
ICD implantation may be considered in selected
asymptomatic BrS patients with inducible VF	IIb	C
during PES using up to 2 extra stimuli.155 Catheter ablation in asymptomatic BrS patients is not recommended.	III	C	© ESC 2022

7.2.5. Early repolarization syndromes

Early repolarization syndrome (ERS) is diagnosed in a patient resuscitated from PVT or VF without any heart disease and the early repolarization pattern (ERP); J-point elevation ≥1 mm in ≥2 adjacent inferior and/or lateral ECG leads (Figure 32). However, ERP is most often a benign finding and the prevalence of ERP has been reported as 5.8% in adults and is more common in young males and athletes. Nonetheless, ERP is over-represented in relatives of SADS cases and of CA survivors. The diagnostic yield and utility of genetic testing is low. High-risk ECG features have been proposed to increase likelihood of ERS: prominent J-waves ≥2 mm, dynamic changes in J-point elevation (.0.1 mV) and J-waves associated with a horizontal or descending ST-segment (Figure 34). ERP with a horizontal ST-segment was associated with arrhythmic risk in an elderly and IVF population. Nonetheless, ERS survivors and relatives of SADS cases also exhibit a higher prevalence of the ascending/upsloping ST segment than controls. At least 40% of ERS patients with VF have subsequent episodes, with 27% suffering multiple episodes. Isoproterenol infusion is effective in acute suppression of recurrent ICD discharges and electrical storm. AADs that block the transient outward potassium current can prevent VF. A retrospective multicentre study showed a reduction of recurrent VF after initiation of quinidine. Phosphodiesterase-3 inhibitors such as cilostazol and milrinone also reduced the recurrence of VF. Ablation of a PVC trigger, usually from the Purkinje system, has an acute success rate of 87–100% and may be effective in preventing recurrence in patients with drug-refractory VF. Detailed electroanatomic mapping may reveal localized structural alterations in 39% of ERS patients. Ablation of these areas successfully suppressed electrical storm and may be a therapeutic option in experienced centres. Whether catheter ablation improves long-term outcomes is currently unknown.

Data for risk stratification of patients with suspected ERS without prior CA are unavailable. In individuals with ERP and unexplained syncope, this panel has recommended that follow-up with an ILR should be considered. As the prognosis of asymptomatic subjects with ERP is good, ICD therapy is usually not indicated. If, however, there is a high-risk ERP and a strong family history of unexplained juvenile SD, then ICD implantation or quinidine may be considered.

BrS, Brugada syndrome; CA, cardiac arrest; ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; PES, programmed electrical stimulation; PVCs, premature ventricular complexes; PVT, polymorphic ventricular tachycardia; RVOT, right ventricular outflow tract; SCD, sudden cardiac death; SD, sudden death; VA, ventricular arrhythmia; VF, ventricular fibrillation. aClass of recommendation. bLevel of evidence.

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----- Start of picture text ----- Patient with ECG suspicious of Brugada Syndrome Sustained V A or No documented V A aborted cardiac arrest Spontaneous type 1 BrS ECG No type I BrS ECG Exclude alternative diagnosis consistent with ECGa General recommendationsb Arrhythmic syncope/ (Class I) nocturnal agonical respiration Y N Sodium channel bloc k er test (Class III) Y Family history o f BrS or SADS Y Syncope N Follow-up N Sodium channel Sodium channel bloc k er test bloc k er test Discharge (Class I) (Class I) Positive Results Results Arrh y thmic Y ICD implant a tion Negative Negative Positive syncope (Class IIa) Further Discharge General N evaluation recommen- Recurrent according dationsb Unexplained symptom a tic V A to ESC (Class I) syncope syncope Guidelines Quinidine Follow-up ILR (Class IIa) (Class IIa) Recurrent symptom a tic V A C a thete r abl a tion (Class IIa) ----- End of picture text -----

Figure 33 Part One. Algorithm for the management of patients with Brugada pattern electrocardiogram.

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----- Start of picture text ----- Sustained V A or aborted cardiac arrest Exclude alternative diagn o sis consistent with ECGa Y Spontaneous t ype 1 N BrS ECG General recommendationsb Sodium channel bloc k er test (Class I) (Class I) ICD implantation (Class I) Results Sodium channel bloc k er test (Class III) Positive Negative Recurren t symptom a tic V A General recommendations(Class I) b alterFunr a thtier ve caevaulse ou a tiof n V A/ f orCA ICD implantation (Class I) Recurren t symptom a tic V A Quinidine (Class IIa) Recurren t symptom a tic V A C a theter abl a tion (Class IIa) ----- End of picture text -----

Figure 33 Part Two. Algorithm for the management of patients with Brugada pattern electrocardiogram. BrS, Brugada syndrome; CA, cardiac arrest; ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; N, No; SADS, sudden arrhythmic death syndrome; VA, ventricular arrhythmia; Y, Yes.[a] Echo, CMR, cardiac CT, CAG indicated according to patient clinical presentation and risk factors.[b] General recommendations: avoidance of drugs that may induce ST-segmentation elevation in right precordial leads (http://www.brugadadrugs.org), avoidance of cocaine and excessive alcohol intake, treatment of fever with antipyretic drugs.

Recommendation Table 44 — Recommendations for the management of patients with early repolarization pattern/syndrome

Recommendations	Classa	Levelb
Diagnosis
It is recommended that the ERP is diagnosed as J-point elevation of≥1 mm in two adjacent inferior and/or lateral ECG leads.1017,1018	I	C
It is recommended that the ERS is diagnosed in a patient resuscitated from unexplained VF/PVT in the presence of ERP.1017,1018	I	C
In an SCD victim with a negative autopsy and medical chart review, and an ante-mortem ECG demonstrating the ERP, the diagnosis of ERS should be considered.1017,1018	IIa	C
First-degree relatives of ERS patients should be considered for clinical evaluation for ERP with additional high-risk features.c,1022,1037	IIa	B

Genetic testing in ERS patients may be considered.1023,1025	IIb	C
Clinical evaluation is not recommended routinely in asymptomatic subjects with ERP.1038,1039	III	C
Risk stratifcation, prevention of SCD and treatment of VA
ICD implantation is recommended in patients with a diagnosis of ERS who have survived a CA.1017	I	B
Isoproterenol infusion should be considered for ERS patients with electrical storm.1017,1030–1032	IIa	B
Quinidine in addition to an ICD should be considered for recurrent VF in ERS patients.922,1030,1033	IIa	B
ILR should be considered in individuals with ERP and at least one risk featured or arrhythmic syncope.1020	IIa	C
PVC ablation should be considered in ERS patients with recurrent VF episodes triggered by a similar PVC non-responsive to medical treatment.1010	IIa	C
ICD implantation or quinidine may be considered in individuals with ERP and arrhythmic syncope and additional risk features.d,1030,1033	IIb	C

Continued

Continued

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ICD implantation or quinidine may be considered in asymptomatic individuals who demonstrate a high-risk IIb C ERP[c] in the presence of a family history of unexplained juvenile SD. ICD implantation is not recommended in asymptomatic III C patients with an isolated ERP.

CA, cardiac arrest; ECG, electrocardiogram; ERP, early repolarization pattern; ERS, early repolarization syndrome; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; PVC, premature ventricular complexes; PVT, ventricular tachycardia; SCD, sudden cardiac death; SD, sudden death; VA, ventricular arrhythmia; VF, ventricular fibrillation. aClass of recommendation. bLevel of evidence. cERP high-risk features: J waves.2 mm, dynamic changes in J point and ST morphology. dHigh-risk ERP: family history of unexplained SD,40 years, family history of ERS.

7.2.6. Catecholaminergic polymorphic ventricular tachycardia

CPVT is a heritable disorder characterized by catecholamineinduced bidirectional VT and PVT in the absence of SHD or ischaemia. The disease has an estimated prevalence of 1 in 10000 (Figure 35).

There are two main genetic types: a dominant disorder due to mutations in the gene encoding for the cardiac ryanodine receptor (RYR2) and a recessive disorder caused by mutations in the cardiac calsequestrin gene (CASQ2). Mutations in TRDN and CALM1-3 have been identified in patients with atypical forms of catecholaminergic VAs. At the present time, however, it is unclear whether they are distinct arrhythmic entities. Patients with KCNJ2 mutations causing Andersen–Tawil syndrome type 1 may sometimes exhibit bidirectional and PVT, but are distinguished by their syndromic associations.

----- Start of picture text ----- Patient with early repolarization pattern N Aborted cardiac arrest Y Arrhythmic syncope N Y At least one risk factor: ICD implantation a (Class I) High risk ERP Family history of juvenile unexplained SD Family history of ERS Recurrent Electrical storm Y N ICD shocks ILR ILR (Class IIa) (Class IIa) Isoproterenol Quinidine ICD implantation (Class IIa) (Class IIa) (Class IIb) Quinidine Quinidine (Class IIa) (Class IIb) At least one risk factor: Recurrence High risk ERPa Family history of juvenile unexplained SD Family history of ERS Catheter ablation of PVC triggers N Y (Class IIa) No further High risk ERPa AND investigation Family history of juvenile unexplained SD (Class III) Y N ILR ILR (Class IIa) (Class IIa) ICD implantation (Class IIb) Quinidine (Class IIb) ----- End of picture text -----

Figure 34 Management of patients with early repolarization pattern/syndrome. ERP, early repolarization pattern; ERS, early repolarization syndrome; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder; N, No; PVC, premature ventricular complex; SD, sudden death; Y, Yes.[a] ERP high risk features: J waves.2 mm, dynamic changes in ST morphology.

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----- Start of picture text ----- Patient with CPVT Aborted cardiac arrest Arrhythmic syncope or Asymptomatic, no documented bidirectional or polymorphic VT V A, but pathogenic mutation General recommendationsa (Class I) Beta-bloc k erb (Class I) Beta-bloc k erb (Class IIa) ICD implantation (Class I) Syncope or exertional PVCs or VT Syncope or exertional PVCs or VT Flecainide (Class IIa) Flecainide (Class IIa) Syncope or documented VT Syncope or documented VT LCSD (Class IIa) ICD implantation (Class IIa) LCSD (Class IIa) ----- End of picture text -----

Figure 35 Management of patients with catecholaminergic polymorphic ventricular tachycardia. CPVT, catecholaminergic polymorphic ventricular tachycardia; ICD, implantable cardioverter defibrillator; LCSD, left cardiac sympathetic denervation; PVC, premature ventricular complex; VA, ventricular arrhythmia; VT, ventricular tachycardia.[a] General recommendations: avoidance of competitive sports, avoidance of strenuous exercise, avoidance of stressful environments.[b] Preferred beta-blockers: nadolol, propranolol.

The clinical manifestations of CPVT usually occur in the first decade of life prompted by physical activity or emotional stress. Most CPVT patients have normal ECG and echocardiogram. Nonetheless, some patients present mild ECG abnormalities, such as sinus bradycardia and prominent U waves. Exercise stress test is the most important diagnostic test, because it elicits the distinguishing bidirectional or PVT that establish the diagnosis (Figure 36). A diagnosis can also be made in the presence of a mutation in genes associated with CPVT. Epinephrine or isoproterenol challenge may be considered when exercise stress testing is not feasible.

Diagnosis in childhood, the lack of beta-blocker therapy, and complex arrhythmias during the exercise stress test on a full dose of betablockers are independent predictors for arrhythmic events. Exercise restriction and beta-blockers without intrinsic sympathomimetic activity are the first-line therapy for CPVT patients. Non-selective beta-blockers such as nadolol and propranolol are preferred. This panel has confirmed the indication to treat genetically positive family members with beta-blockers, even in the absence of documented exercise- or stress-induced VAs. Data suggest that flecainide significantly reduces the VA burden in CPVT patients and should be considered in addition to beta-blockers when control of arrhythmias is incomplete. In selected

patients who show intolerance to beta-blocker therapy, pharmacological therapy with flecainide alone is an option.

Maximal protection with beta-blockers, flecainide and ICD is indicated in survivors of a CA. An ICD should also be considered in CPVT patients with breakthrough VA on beta-blockers and flecainide. The ICD should, however, be programmed with long delays and high rates before defibrillation, because initiating bidirectional VT responds less effectively to defibrillation than subsequent PVT/VF, and painful shocks can trigger further and incessant arrhythmias.

LCSD has been proposed as an additional therapy in patients in whom pharmacological treatment is not effective or feasible. Although LCSD reduces the recurrence of major cardiac events in previously symptomatic patients, one-third of patients still suffer recurrences of arrhythmia. Therefore, LCSD has not been considered to be a replacement for ICD therapy but a complementary therapy in symptomatic patients.

A recent systematic review of 53 studies including CPVT patients with an ICD concluded that secondary prevention patients managed with OMT, LCSD and exercise restriction could reduce ICD use. This observation was supported by a subsequent multicentric investigation showing that all the three SCD observed occurred in patients with an ICD. At present it seems premature, on the base of this evidence, to demote ICD implant in survivors of CA with CPVT.

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----- Start of picture text ----- Bidirectional PVCs during exercise II III ----- End of picture text -----

Figure 36 Exercise test of a patient with catecholaminergic polymorphic ventricular tachycardia. PVC, premature ventricular complex.

Recommendation Table 45 — Recommendations for the management of patients with catecholaminergic polymorphic ventricular tachycardia

Recommendations	Classa	Levelb
Diagnosis
It is recommended that CPVT is diagnosed in the presence of a structurally normal heart, normal ECG, and exercise- or emotion-induced bidirectional, or PVT.	I	C
It is recommended that CPVT is diagnosed in patients who are carriers of a mutation in disease-causing genes.	I	C
Genetic testing and genetic counselling are indicated in patients with clinical suspicion or clinical diagnosis of CPVT.	I	C
Epinephrine or isoproterenol challenge may be considered for the diagnosis of CPVT when an exercise test is not possible.	IIb	C
General recommendations
Avoidance of competitive sports, strenuous exercise, and exposure to stressful environments is recommended in all patients with CPVT.	I	C
Therapeutic interventions
Beta-blockers, ideally non-selective (nadolol or propranolol) are recommended in all patients with a clinical diagnosis of CPVT.1045,1048,1059	I	C
ICD implantation combined with beta-blockers andfecainide is recommended in CPVT patients after aborted CA.1045,1047,1060	I	C
		Continued

Therapy with beta-blockers should be considered for genetically positive CPVT patients without phenotype.1047,1050	IIa	C
LCSD should be considered in patients with diagnosis of CPVT when the combination of beta-blockers andfecainide at therapeutic dosage are either not effective, not tolerated, or contraindicated.1056	IIa	C
ICD implantation should be considered in patients with CPVT who experience arrhythmogenic syncope and/or documented bidirectional/PVT while on highest tolerated beta-blocker dose and onfecainide.1047,1050	IIa	C
Flecainide should be considered in patients with CPVT who experience recurrent syncope, polymorphic/bidirectional VT, or persistent exertional PVCs, while on beta-blockers at the highest tolerated dose.1052,1053,1060	IIa	C
PES is not recommended for stratifcation of SCD risk. III

7.2.7. Short QT syndrome

Short QT syndrome (SQTS) is a rare genetic disorder characterised by a short QT interval, premature AF and VF in the context of a structurally normal heart. It has been associated with gain of function mutations in KCNH2, KCNQ1 and loss of

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----- Start of picture text ----- Short QT syndrome ----- End of picture text -----

Figure 37 Short QT syndrome.

function in SLC4A. This panel proposed two QTc cut-off threshold for diagnosis: A QTc ≤320 ms alone, or B a QTc ≤360 ms combined with a family history of SQTS, aborted CA in the absence of heart disease or pathogenic mutation (Figure 37). The disease has high lethality in all age groups, including the first months of life. The probability of a first CA by the age of 40 years is.40%. While an ICD is used for secondary prevention, primary prevention remains contentious and is based upon prior symptoms and QTc interval. Quinidine is currently the best supported AAD, but should be monitored for excessive QT prolongation, while isoprenaline may be considered in electrical storm. Drugs that shorten QT interval should be avoided, e.g. nicorandil. Loop recorder implantation should be considered in children and young asymptomatic SQTS patients.

Recommendation Table 46 — Recommendations for the management of patients with short QT syndrome

Recommendations	Classa	Levelb
Diagnosis
It is recommended that SQTS is diagnosed in the presence of a QTc≤360 ms and one or more of the following: (a) a pathogenic mutation, (b) a family history of SQTS, (c) survival from a VT/VF episode in the absence of heart disease.1061,1068	I	C
Genetic testing is indicated in patients diagnosed with SQTS.1063	I	C

Continued

	SQTS should be considered in the presence of a QTc≤320 ms.1064–1067,1073,1074 IIa C SQTS should be considered in the presence of a QTc≥320 ms and≤360 ms and arrhythmic syncope. IIa C SQTS may be considered in the presence of a QTc≥320 ms and≤360 ms and a family history of SD at age,40 years. IIb C Risk stratifcation, SCD prevention and treatment of VA ICD implantation is recommended in patients with a diagnosis of SQTS who: (a) are survivors of an aborted CA and/or (b) have documented spontaneous sustained VT.1063 I C ILR should be considered in young SQTS patients. IIa C ICD implantation should be considered in SQTS patients with arrhythmic syncope. IIa C Quinidine may be considered in (a) SQTS patients who qualify for an ICD but present a contraindication to the ICD or refuse it, and (b) asymptomatic SQTS patients and a family history of SCD.1069–1071 IIb C Isoproterenol may be considered in SQTS patients with an electrical storm.1075 IIb C PES is not recommended for SCD risk stratifcation in SQTS patients. III C	© ESC 2022

CA, cardiac arrest; ICD, implantable cardioverter defibrillator; ILR, implantable loop recorder, SCD, sudden cardiac death; SD, sudden death; SQTS, short QT syndrome; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

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8. Special aspects in selected populations

8.1. Pregnant patients and peri-partum cardiomyopathy

Pregnancy and the post-partum period contribute a significant risk in women with arrhythmic heart disease and is covered in the 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. New-onset VT may present during pregnancy and risk of recurrent VT is higher in patients with previous VT and SHD. Peri-partum cardiomyopathy (PPCM) should be ruled out in the case of new-onset VT during the last 6 weeks of pregnancy or in the early post-partum period. A genetic contribution may be present in up to 20% of patients with PPCM (in particular titin-truncating variants) and future studies should reveal if genetic testing plays a role in PPCM patients with a positive family history.

8.1.1. Electrocardioversion and implantable

In LQTS (LQT2 in particular), risk of cardiac events increases substantially in the post-partum period (up to one year after delivery). Therefore, it is important to continue beta-blocker therapy throughout pregnancy and post-partum. Continuation of beta-blocker treatment is recommended in LQTS and CPVT and should be considered in ARVC. No additional risk by pregnancy is known in women with BrS ( ESC CardioMed chapter 53.6).

In patients with PPCM, use of bromocriptine as disease-specific therapy in addition to standard heart failure therapy has shown promising results in two clinical trials.

8.1.3. Catheter ablation

In planned pregnancies, symptomatic tachyarrhythmia should be treated by catheter ablation before pregnancy. If catheter ablation is indicated in a pregnant patient, one should avoid the procedure in the first trimester, and electroanatomical mapping-guided procedures should be preferred.

cardioverter defibrillator therapy in pregnancy

Cardioversion seems safe in all phases of pregnancy and case reports show neither compromise in fetal blood flow nor initiation of preterm labour. Foetal heart rate should be routinely controlled after cardioversion. If an ICD is indicated, ICD implantation should be performed beyond 8 weeks of gestation with radiation protection by experienced operator teams. Echocardiographic guidance or a 3D mapping system may be helpful in ICD implantation to avoid radiation. In pregnant patients with existing ICD, routine ICD interrogation is recommended prior to delivery. In patients with PPCM, thresholds for early ICD implantations are higher than in other conditions because of a high rate of spontaneous recovery after delivery. WCD have been suggested to temporarily prevent SCD during the first 3–6 months after diagnosis of PPCM with LVEF ≤35%, while awaiting recovery.

8.1.2. Pharmacological treatment

Pharmacological treatment of arrhythmias and heart failure in pregnant women should follow treatment in non-pregnant patients with avoidance of drugs contraindicated in pregnancy, such as ACE inhibitors, ARB inhibitors/ARNI and renin inhibitors. The first trimester is associated with the greatest teratogenic risk. Start of pharmacological therapy is advised to begin at the latest possible point in the pregnancy and with the lowest effective dose. Drug exposure in the second and third trimestera may confer adverse effects on foetal growth and development as well as increasing the risk of pro-arrhythmia.

It is recommended to check drugs and safety data before initiation of a new drug during pregnancy, according to the 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. From this list, AADs can be summarized as followed:

• Well tolerated: sotalol, oral verapamil

• Use only if potential benefit outweighs potential risk: bisoprolol, carvedilol, digoxin, diltiazem (possible teratogenic effects), disopyramide (uterine contractions), flecainide, lidocaine, metoprolol, nadolol, propranolol, verapamil IV, quinidine

• Inadequate data: Ivabradine, mexiletine, proprafenone, vernakalant

• Contraindicated: amiodarone, atenolol, dronedarone.

Recommendation Table 47 — Recommendations for the prevention of sudden cardiac death and management of ventricular arrhythmia during pregnancy

Recommendations	Classa	Levelb
Acute management of VA
During pregnancy, electrical cardioversion is recommended for sustained VT.1084	I	C
For acute conversion of haemodynamically tolerated SMVT during pregnancy, a beta-blocker, sotalol,fecainide, procainamide, or overdrive ventricular pacing should be considered.	IIa	C
Long-term management of VA
If ICD implantation is indicated during pregnancy, implantation is recommended with optimal radiation protection.1087,1107	I	C
Continuation of beta-blockers is recommended during pregnancy and post-partum in women with LQTS or CPVT.955,1094–1096	I	C
Continuation of beta-blockers should be considered during pregnancy in women with ARVC.1097–1099	IIa	C
Oral metoprolol, propranolol, or verapamil should be considered for long-term management of idiopathic sustained VT during pregnancy.	IIa	C
Catheter ablation using non-fuoroscopic mapping systems should be considered, preferably after the frst trimester, in women with highly symptomatic recurrent SMVT refractory or who are intolerant to AADs.1105	IIa	C

AAD, anti-arrhythmic drug; ARVC, arrhythmogenic right ventricular cardiomyopathy; CPVT, catecholaminergic polymorphic ventricular tachycardia; ICD, implantable cardioverter defibrillator; LQTS, long QT syndrome; SMVT, sustained monomorphic VT; VA, ventricular arrhythmia; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence.

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8.2. Heart transplantation

Patients listed for HTX are exposed to an SCD risk and have a high incidence of VA. Data from large registries suggest a survival benefit from ICDs. The only randomized study including patients listed for HTX was prematurely stopped because of low enrolment. There are no data regarding the role of WCD in patients listed for HTX. The median expected time on the waiting list, 8–16 months, needs to be considered. However, this panel shares the opinion that a WCD may be an alternative for an ICD in selected patients waiting for HTX.

In post-HTX patients, SCD is responsible for around 10% of deaths. Transplant rejection and allograft vasculopathy are associated with SCD; therefore, ICD implantation may be appropriate in selected high-risk patients.

Recommendation Table 48 — Recommendations for the prevention of sudden cardiac death before and after heart transplantation

Recommendations	Classa	Levelb C C C © ESC 2022
Prior to heart transplant
In patients awaiting heart transplantation, ICD implantation for primary prevention should be considered.1108,1111,1112	IIa	C
In patients awaiting heart transplantation, WCD may be considered.1109,1113,1119	IIb	C
Post heart transplant
In selected transplanted patients with cardiac allograft vasculopathy or treated rejection, ICD implantation may be considered.1114,1116	IIb	C

ICD, implantable cardioverter defibrillator; WCD, wearable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

8.3. Sudden cardiac death in athletes

The incidence of SCD in athletes increases with age. In apparently healthy athletes (.35 years), the estimated incidence of SCD ranges from 2 to 6.3 per 100 000 participant-years. In comparison, in young competitive athletes (≤35 years) the incidence of fatal events is significantly lower, 0.4–3 per 100 000 participantyears. Women athletes are at low risk of SCD; on average, 1 in 14 SCD in athletes occurs in women.

Pre-participation cardiovascular evaluation offers the potential to identify athletes at-risk for cardiovascular disease before onset of symptoms. The evaluation protocol needs to be adapted to the age of the athlete to account for age-specific cardiovascular disease. Pre-participation evaluation, including medical history, physical examination, and ECG, appears effective in identifying cardiovascular disease in young athletes (≤35 years of age) by identification of relevant symptoms (e.g. exertional syncope) or ECG abnormalities consistent with inheritable cardiomyopathies or channelopathies. Although echocardiography can increase the sensitivity of screening for SHD,

it is unfeasible as a routine test in mass screening. More cardiovascular diseases are identified by serial (annual) evaluations of adolescent athletes. The prevalence of false-positive results strongly depends on the criteria used to define an ECG ‘ ’ as abnormal. Additional tests, such as echocardiography, 24-hour Holter monitoring, stress testing, and CMR, are requested for athletes who had positive findings at the initial evaluation. Athletes diagnosed with clinically relevant cardiovascular disease are managed according to available ESC Guidelines. In middle-aged/senior athletes, the most common cause of SCD is CAD. Before engaging in a vigorous physical activity, asymptomatic middle-aged/senior athletes should be evaluated using risk score systems such as the ESC SCORE2.

Excellent rates of survival with favourable neurological outcome after CA has been reported in sports centres equipped with AED. This justifies the efforts for implementing emergency programs for SCD prevention, with distribution of AED in sports arenas and training of coaches and staff to perform CPR and defibrillation.

Recommendation Table 49 — Recommendations for risk stratification and prevention of sudden cardiac death in athletes

Recommendations	Classa	Levelb	© ESC 2022
In athletes with positive medical history, abnormal physical examination, or ECG alterations, further investigations including echocardiography and/or CMR to confrm (or exclude) an underlying disease are recommended.1123,1133,1135	I	C
It is recommended that athletes diagnosed with a cardiovascular disease associated with SCD are managed according to current guidelines for sports eligibility.	I	C
It is recommended that staff at sporting facilities are trained in CPR and in the use of AED.93,1137	I	C
Pre-participation cardiovascular evaluation of competitive athletes should be considered.46,1122,1123,1127	IIa	C
It should be considered that cardiovascular evaluation of young (,35 years) competitive athletes includes history, physical examination, and 12-lead ECG.1123,1126,1130,1140	IIa	C
The cardiovascular risk of middle-aged and elderly individuals should be evaluated before engaging in strenuous sports through established scores such as the SCORE2 risk chart.46,1141,1142	IIa	C

AED, automated external defibrillator; CMR, cardiac magnetic resonance; CPR, cardiopulmonary resuscitation; ECG, electrocardiogram; SCD, sudden cardiac death. aClass of recommendation. bLevel of evidence.

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8.4. Wolff–Parkinson–White syndrome

In patients with Wolff–Parkinson–White (WPW) syndrome, the most common arrhythmia is AV re-entry tachycardia (AVRT; – 80%), followed by AF (20 30%). SCD secondary to pre-excited AF resulting in VF is the most feared manifestation of WPW syndrome. The risk of CA/VF in untreated WPW patients has been estimated at 0.9–2.4 per 1000 person-year. The management of WPW patients has recently been reviewed in the 2019 ESC Guidelines for the management of patients with SVT and updated with a particular focus on athletes in 2020. In patients with ventricular pre-excitation and symptomatic AVRT, catheter ablation is recommended (class I). In asymptomatic patients with ventricular pre-excitation, both invasive (class IIa) and non-invasive (class IIb) assessment are options for risk stratification for SCD. While catheter ablation is recommended for asymptomatic accessory pathways with high-risk features (class I), clinical follow-up (class IIa), or catheter ablations (class IIb) are options based on informed patient choice. This decision should take into account the location of the accessory pathway, the local ablation experience and the fact that symptomatic arrhythmias will frequently develop during followup. For the paediatric population, SVT due to WPW can usually be managed pharmacologically, and accessory pathways often lose antegrade conduction in the first years of life. In children with asymptomatic accessory pathways, risk stratification is not recommend before the age of 8 years.

8.5. Prevention of sudden cardiac death in the elderly

Age is a strong risk factor for death. In several studies, advanced age was one of the factors associated with a reduced expected benefit from ICD treatment. In patients with ischaemic cardiomyopathy enrolled in MADIT-II trial, a risk scheme composed of 5 clinical factors including age.70 years was predictive of the absence of long-term benefit conferred by the ICD. In a recent analysis of ICD patients enrolled in four MADIT studies, age,75 years was a predictor of VT/VF whereas age ≥75 years was a predictor of non-arrhythmic mortality. Consistently, in the recent randomized DANISH trial in patients with non-ischaemic heart failure, the association between the ICD and survival decreased linearly with increasing age, while an age cut-off at ≤70 years yielded the highest survival. Contemporary non-randomized data corroborate these findings. In the EU-CERT-ICD prospective cohort study in patients with CAD or cardiomyopathies with indication for primary prevention ICD implantation, no ICD benefit was observed in patients aged ≥75 years. In contrast, there was a significant survival benefit in patients aged,75 years. Further retrospective data are in line with this observation.

Biological age may vary in part according to comorbidities. Indeed, comorbidities significantly influence survival of ICD recipients and a high comorbidity index is associated with less survival gain in primary or secondary prevention ICD patients. Therefore, a simple age cut-off cannot guide the decision on ICD implantation adequately and the ICD indication in elderly patients should be based on a personalized assessment considering the overall condition and comorbidities.

Recommendation Table 50 — Recommendations for implantable cardioverter defibrillator implantation in the elderly

Recommendations	Classa	Levelb	© ESC 2022
In elderly patients in whom a beneft from the defbrillator is not expected due to the patient’s age and comorbidities, omission of ICD implantation for primary prevention may be considered.647,1150,1152	IIb	B

ICD, implantable cardioverter defibrillator. aClass of recommendation. bLevel of evidence.

9. Key messages

9.1. General aspects

• Increased availability of public access defibrillators and community training in basic life support are key elements to improve survival of out-of-hospital cardiac arrest victims.

• Risk calculators for SCD and VA implemented in clinical practice need to meet agreed high standards for the development, external validation, and reporting of prediction models.

• Patients with genetic cardiomyopathies and arrhythmia syndromes require genetic testing as a routine part of their care.

• Genetic testing and counselling require access to an expert multidisciplinary team.

• A systematic workup of cardiac arrest survivors requires a multimodal approach.

• A comprehensive autopsy is recommended in all cases of sudden death under 50 years and is desirable in all sudden death victims.

• Clinical and genetic evaluation of SADS decedents and their families leads to a diagnosis of genetic heart disease in a substantial proportion of families.

• An electrical storm refractory to drug treatment requires the availability of advanced catheter ablation techniques, mechanical circulatory support, and autonomic modulation.

• When considering ICD therapy benefit, competing risk factors for non-arrhythmic death and the patient’s wishes and quality of life need to be taken into account.

9.2. Structural heart disease

• Catheter ablation is recommended in CAD patients with recurrent symptomatic SMVT despite chronic amiodarone therapy.

• Catheter ablation is the first-line treatment for PVC-induced cardiomyopathy.

• In HNDCM/DCM patients, indication for primary prevention ICD implantation should not be restricted to an LVEF ≤35%. Additional risk factors (e.g. CMR and genetics) are important to consider.

• Patients with an LMNA mutation require specific risk stratification for SCD.

• ARVC patients have a high rate of appropriate ICD interventions which may not necessarily be classified as lifesaving.

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• A validated risk calculator (HCM Risk-Kids score) is useful to assess the risk for SCD in HCM patients younger than 16 years.

• Myotonic dystrophy patients with palpitations suspected of arrhythmia, syncope or aborted sudden death need to be evaluated by invasive electrophysiological study.

• In patients with repaired tetralogy of Fallot and monomorphic VT, catheter ablation is the preferred treatment.

10.3. Idiopathic premature ventricular complexes/ventricular tachycardia

• The beneficial role of catheter ablation or anti-arrhythmic drug treatment in patients with asymptomatic, frequent PVCs and preserved cardiac function needs to be determined.

10.4. Coronary artery disease

9.3. Primary electrical disease

• Nadolol or propranolol are the preferred beta-blockers in LQTS and CPVT patients.

• In asymptomatic LQTS patients the arrhythmic risk (1-2-3 Risk calculator) may be useful to calculate.

• A type 1 Brugada ECG pattern provoked by sodium channel blocker test in the absence of other findings does not diagnose the BrS.

• SCD risk stratification in asymptomatic BrS patients with a spontaneous type 1 pattern remains controversial.

• Routine catheter ablation is not recommended in asymptomatic BrS patients.

• The diagnosis of idiopathic VF requires exclusion of an underlying structural, channelopathic, or metabolic aetiology.

• ERP can be a benign finding and is distinct from ERS.

• Left cardiac denervation plays an important role in the management of CPVT and LQTS patients.

10. Gaps in evidence

10.1. General aspects

• Accurate screening tests to detect heart conditions associated with SCD in asymptomatic individuals in the general population are required.

• In patients with SHD, the optimal time interval between repeated non-invasive and invasive prognostic tests, in case of a negative test, is unknown.

• Improved assessment of genetic variants of uncertain significance and likely pathogenic variants is needed.

• The utility of polygenic risk scores in patients at risk of SCD requires investigation.

10.2. Structural heart disease—general

• The long-term safety and efficacy of S-ICDs is unknown.

• The role of primary preventive ICD therapy in patients with SHD and mildly reduced or preserved ejection fraction has not been studied systematically.

• The optimal techniques to undertake VT substrate mapping and ablation in SHD remain to be determined.

• The role of ICD implantation in end-stage heart failure patients supported by current-generation, continuous-flow LVADs is unclear.

• It is unknown which patients with chronic CAD and severely impaired LVEF are at low risk for SCD.

• The role of LGE-CMR for risk stratification for SCD in chronic CAD is unclear.

• RCTs are needed to determine the role of ICDs after successful VT ablation in chronic CAD with mildly reduced or preserved LVEF.

10.5. Cardiomyopathies

• It is unknown if PVC-induced cardiomyopathy is a diagnosis on its own or if an underlying predisposition is needed.

• The predictive value of LGE-CMR findings (e.g. pattern and amount of LGE) for individual risk stratification for SCD in patients with cardiac sarcoidosis, HCM, and DCM/HNDC is unclear.

• Studies are needed to determine the role of PES in patients with cardiac sarcoidosis and DCM/HNDC who have a mildly reduced or preserved cardiac function and LGE on CMR.

• Prospective data on the association between intensity and duration of exercise and manifestation and severity of the phenotype in healthy ARVC mutation carriers are lacking.

• The beneficial role of ICDs after successful ablation in ARVC patients who present with haemodynamically tolerated VT needs to be studied.

• Data on clinical outcome, predictors for arrhythmic events, and indication for treatment, including ICD therapy, in patients with biventricular and left-dominant arrhythmogenic cardiomyopathy are required.

10.6. Valvular heart disease

• There is a lack of knowledge to identify patients with MVP at risk for VA and SCD.

10.7. Congenital heart disease

• There is a lack of knowledge regarding the absolute risk for VA and SCD in CHD that have undergone repair with contemporary surgical approaches.

10.8. Primary electrical disease

• Robust evidence is required to support the prophylactic use of the ICD on top of medical therapy with beta-blockers and genespecific therapy in LQTS patients.

• More data are required to determine the role of LCSD and ICD in high-risk LQTS patients who do not tolerate medical therapy.

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• Improved diagnostic and risk stratification tools for asymptomatic Brugada patients and suspected early repolarization syndrome are needed.

• The role of endo-epicardial mapping to identify localized structural alterations potentially related to IVF and targeted catheter ablation needs to be further studied.

• Long-term data are required on the efficacy of the ICD vs. no ICD in CPVT survivors of cardiac arrest.

• It is poorly understood why women are at low risk of sport-related SCD.

11. ‘What to do’ and ‘what not to do’ messages from the Guidelines

Recommendations	Classa	Levelb
Recommendations for public basic life support and access to automated external defbrillator
It is recommended that public access defbrillation be available at sites where cardiac arrest is more likely to occur.c	I	B
Prompt CPR by bystanders is recommended at OHCA.	I	B
It is recommended to promote community training in basic life support to increase bystander CPR rate and AED use.	I	B
Recommendations for genetic testing
Genetic testing is recommended when a condition is diagnosed in a living or deceased individual with a likely genetic basis and a risk of VA and SCD.	I	B
When a putative causative variant isfrst identifed, evaluation for pathogenicity is recommended using an internationally accepted framework.	I	C
When a Class IV or Class V variant has been identifed in a living or deceased individual with a condition that carries a risk of VA and SCD, genetic testing offrst-degree and symptomatic relatives and obligate carriers is recommended.	I	C
It is recommended that genetic testing and counselling on its potential consequences should be undertaken by an expert multidisciplinary team.	I	C
It is recommended that Class III variants (of uncertain signifcance) and Class IV variants should be evaluated for segregation in families where possible, and the variant re-evaluated periodically.	I	C
It is not recommended to undertake genetic testing in index patients with insuffcient evidence of a genetic disease.	III	C
Recommendations for evaluation of patients presenting with newly documented ventricular arrhythmia
In patients with newly documented VA (frequent PVCs, NSVT, SMVT), a baseline 12-lead ECG, recording of the VA on 12-lead ECG, whenever possible, and an echocardiogram are recommended asfrst-line evaluation.	I	C
Recommendations for evaluation of sudden cardiac arrest survivors
The investigation of a SCA survivor without obvious extra-cardiac cause is recommended to be overseen by a multidisciplinary team.	I	B
In electrically unstable patients after SCA, with suspicion of ongoing myocardial ischaemia, a coronary angiogram is indicated.	I	C
In SCA survivors, collection of blood samples at presentation is recommended for potential toxicology and genetic testing.	I	B
Retrieval of recordings from CIEDs and wearable monitors is recommended for all SCA survivors.	I	B
In SCA survivors, repeated 12-lead ECGs during stable rhythm (including high precordial lead ECG) as well as continuous cardiac monitoring are recommended.	I	B
Echocardiography is recommended for evaluation of cardiac structure and function in all SCA survivors.	I	C
Coronary imaging and CMR with LGE are recommended for evaluation of cardiac structure and function in all SCA survivors without a clear underlying cause.	I	B
Sodium channel blocker test and exercise testing is recommended in SCA survivors without a clear underlying cause.	I	B

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Recommendations for evaluation of sudden death victims	Recommendations for evaluation of sudden death victims
Investigation of unexpected SD, especially in case of suspicion of inherited disease, should be made a public health priority.	I	B
In cases of SD, it is recommended to collect a detailed description of circumstances of death, symptoms prior to death, the family history, and to review prior medicalfles.	I	B
A comprehensive autopsy is recommended, ideally, in all cases of unexpected SD, and always in those under 50 years of age.	I	B
In cases of SCD, it is recommended to retain samples suitable for DNA extraction and consult a cardiac pathologist when an inherited cause is suspected or the cause of death unexplained.	I	B
Toxicology screens are recommended in SD cases with uncertain cause of death.	I	B
For SCD where the cause is known or suspected to be heritable, genetic testing targeted to the cause is recommended.	I	B
Following SADS, post-mortem genetic testing targeted to primary electrical disease is recommended when the decedent is young (,50 years of age) and/or the circumstances and/or family history support a primary electrical disease.	I	B
When an autopsy diagnoses possible heritable cardiac disease, it is recommended to referfrst-degree relatives for cardiac assessment in a specialized clinic.	I	B
In non-autopsied cases of SD where inherited cardiac disease is suspected, it is recommended to referfrst-degree relatives for cardiac assessment in a specialized clinic.	I	B
Recommendations for evaluation of relatives of sudden arrhythmic death syndrome decedents
Following SADS, hypothesis-free post-mortem genetic testing using exome or genome sequencing is not recommended.	III	B
Familial evaluation of SADS decedents is recommended: • forfrst-degree relatives • for relatives who must carry a mutation based on analysis of the family history • for relatives with suspicious symptoms • when the decedent’s age is,50 years or if there are other circumstantial data or family history to suggest heritable disease.	I	B
Familial evaluation of SADS decedents is recommended to include genetic testing when post-mortem genetic testing in a SADS decedent detects a pathogenic mutation.	I	B
Baseline familial evaluation of SADS decedents is recommended to include taking a medical history and performing physical examination, standard- and high-precordial lead ECG, echocardiography, and exercise testing.	I	B
In SADS families without a diagnosis after clinical evaluation, follow-up is recommended for children of decedents until they reach adulthood.	I	C
In SADS families without a diagnosis after clinical evaluation, follow-up is not recommended for asymptomatic adults who can be discharged with advice to return if they develop symptoms or if the family history changes.	III	C
Recommendations for treatment of reversible conditions
Withdrawal of offending agents is recommended whenever drug-induced VA are suspected.	I	B
Investigation for reversible causes (e.g. electrolyte imbalances, ischaemia, hypoxaemia, fever)d is recommended in patients with VA.	I	C
Recommendations for the acute treatment of sustained ventricular tachycardia and electrical storm
DC cardioversion is recommended as thefrst-line treatment for patients with haemodynamically not-tolerated SMVT.	I	B
DC cardioversion is recommended as thefrst-line treatment for patients presenting with tolerated SMVT provided that the anaesthetic/sedation risk is low.	I	C
In patients presenting with a haemodynamically tolerated idiopathic VT, treatment with intravenous beta-blocker (RVOT VT) or verapamil (fascicular VT) is recommended.	I	C
Intravenous verapamil is not recommended in broad QRS complex tachycardia of unknown mechanism.	III	B
Mild to moderate sedation is recommended in patients with electrical storm to alleviate psychological distress and reduce sympathetic tone.	I	C
Antiarrhythmic therapy with beta-blockers (non-selective preferred) in combination with intravenous amiodarone is recommended in patients with SHD and electrical storm unless contraindicated.	I	B

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Intravenous magnesium with supplementation of potassium is recommended in patients with TdP.	I	C
Isoproterenol or transvenous pacing to increase heart rate is recommended in patients with acquired LQT syndrome and recurrent TdP despite correction of precipitating conditions and magnesium.	I	C
Catheter ablation is recommended in patients presenting with incessant VT or electrical storm due to SMVT refractory to AADs.	I	B
Recommendations for treatment with heart failure medication
Optimal medical treatment including ACE-I/ARB/ARNIs, MRAs, beta-blockers, and SGLT2 inhibitors is indicated in all heart failure patients with reduced EF.	I	A
Recommendations for implantable cardioverter defbrillation implantation (general aspects)
Implantation of a cardioverter defbrillator is only recommended in patients who have an expectation of good quality survival.1 year.	I	C
It is not recommended to implant an ICD in patients with incessant VAs until the VA is controlled.	III	C
Recommendations for secondary prevention of sudden cardiac death
ICD implantation is recommended in patients with documented VF or haemodynamically not-tolerated VT in the absence of reversible causes.	I	A
Recommendations for adding cardiac resynchronization therapy to implantable cardioverter defbrillator
When an ICD is indicated, it is recommended to evaluate whether the patient could beneft from CRT-defbrillator.	I	C
Recommendations for optimization of device programming
Optimization of ICD programming is indicated to avoid inappropriate and unnecessary therapies and to reduce mortality.	I	A
In single- or dual-chamber ICD patients without bradycardia pacing indications, it is recommended to minimize ventricular pacing.	I	A
Programming of prolonged detection settings is indicated (duration criteria of at least 6–12 s or 30 intervals).	I	A
It is recommended to program the slowest tachycardia therapy zone limit≥188 b.p.m. in primary prevention ICD patients.	I	A
In patients with SHD, programming of at least one ATP therapy is recommended in all tachyarrhythmias zones.	I	A
It is recommended to program algorithms for SVT vs. VT discrimination for tachycardias with rates up to 230 b.p.m.	I	B
It is recommended to activate lead failure alerts.	I	B
Remote monitoring is recommended to reduce the incidence of inappropriate shocks.	I	B
Programming of burst ATP as afrst attempt is recommended over ramp ATP.	I	B
For S-ICDs, a dual detection zone confguration is recommended with activation of discrimination algorithm in the lower conditional shock zone	I	B
Recommendations for concomitant treatment to avoid inappropriate implantable cardioverter defbrillator therapy
Catheter ablation is recommended for ICD patients with recurrent SVT resulting in inappropriate ICD therapies.	I	C
Pharmacological treatment or catheter ablation is recommended in patients with AF-related inappropriate ICD therapies despite optimal ICD programming.	I	C
Recommendation for psychosocial management after implantable cardioverter defbrillator implantation
Assessment of psychological status and treatment of distress is recommended in ICD patients.	I	C
Communication between patient and physician/healthcare professional is recommended to address ICD-related concerns and to discussquality-of-life issues before ICD implantation and duringdiseaseprogression.	I	C
		Continued

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Recommendations for prevention of implantable cardioverter defbrillator complications	Recommendations for prevention of implantable cardioverter defbrillator complications
Single-chamber ICD is recommended over dual-chamber ICD in primary prevention patients without current or expected indication for atrial or AV sequential pacing due to a lower risk of device-related complications.	I	A
Recommendations for end-of-life issues in implantable cardioverter defbrillator carriers
Informed discussion with patient and family about ICD deactivation options and shared decision-making is indicated prior to implantation and in case of signifcant health status deterioration.	I	C
Recommendations for treatment of ventricular arrhythmia in acute coronary syndrome and vasospasm
Intravenous beta-blocker treatment is indicated for patients with recurrent PVT/VF during STEMI unless contraindicated.	I	B
Prophylactic treatment with AADs (other than beta-blockers) is not recommended in ACS.	III	B
Recommendations for risk stratifcation and treatment of ventricular arrhythmia early after myocardial infarction
Early (before discharge) assessment of LVEF is recommended in all patients with acute MI.	I	B
In patients with pre-discharge LVEF≤40%, re-evaluation of LVEF 6–12 weeks after MI is recommended to assess the potential need for primary prevention ICD implantation.	I	C
Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in chronic coronary artery disease
In patients with syncope and previous STEMI, PES is indicated when syncope remains unexplained after non-invasive evaluation.	I	C
ICD therapy is recommended in patients with CAD, symptomatic heart failure (NYHA class II–III), and LVEF≤35% despite≥3 months of OMT.	I	A
In patients with CAD, prophylactic treatment with AADs other than beta-blockers is not recommended.	III	A
ICD implantation is recommended in patients without ongoing ischaemia with documented VF or haemodynamically not-tolerated VT occurring later than 48 h after MI.	I	A
In patients with CAD and recurrent, symptomatic SMVT or ICD shocks for SMVT despite chronic amiodarone therapy, catheter ablation is recommended in preference to escalating AAD therapy.	I	B
Recommendations for sudden cardiac death prevention in patients with coronary anomalies
Cardiac stress imaging during physical exercise is recommended in addition to cardiopulmonary exercise test in patients with anomalous aortic origin of a coronary artery with an interarterial course to confrm/exclude myocardial ischaemia.	I	C
Cardiac stress imaging during physical exercise is recommended in addition to cardiopulmonary exercise test after surgery in patients with anomalous aortic origin of a coronary artery with a history of aborted CA.	I	C
Surgery is recommended in patients with anomalous aortic origin of a coronary artery with CA, syncope suspected to be due to VAs or angina when other causes have been excluded.	I	C
Recommendations for the management of patients with idiopathic premature ventricular complexes/ventricular tachycardia
Regular assessment of ventricular function of patients with PVC burden.10% and normal ventricular function is indicated.	I	C
Catheter ablation asfrst-line treatment is recommended for symptomatic idiopathic VT/PVCs from the RVOT or the left fascicles.e	I	B
Beta-blockers or non-dihydropyridine CCB are indicated in symptomatic patients with idiopathic VT/PVCs from an origin other than the RVOT or the left fascicles.	I	C
Catheter ablation is not recommended in children,5 years of age or,10 kg weight except when previous medical therapy fails or when VT is not haemodynamically tolerated.	III	C
Amiodarone as afrst-line treatment is not recommended in patients with idiopathic VTs/PVCs.	III	C
Verapamil is not recommended in children,1 year of age with PVC/VT, particularly if they have signs of heart failure or concurrent use of other AADs.	III	C
Recommendations for the management of patients with premature ventricular complex-induced or aggravated cardiomyopathy
In patients with a cardiomyopathy suspected to be caused by frequent and predominately monomorphic PVCs, catheter ablation is recommended.	I	C
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Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in dilated cardiomyopathy/hypokinetic non-dilated cardiomyopathy	Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in dilated cardiomyopathy/hypokinetic non-dilated cardiomyopathy	Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in dilated cardiomyopathy/hypokinetic non-dilated cardiomyopathy
Genetic testing (including at leastLMNA,PLN,RBM20, andFLNCgenes) is recommended in patients with DCM/HNDCM and AV conduction delay at,50 years, or who have a family history of DCM/HNDCM or SCD in afrst-degree relative (at age,50 years).	I	B
Participation in high-intensity exercise including competitive sports is not recommended for individuals with DCM/HNDCM and a LMNAmutation.	III	C
ICD implantation is recommended in patients with DCM/HNDCM, who survive SCA due to VT/VF or experience haemodynamically not-tolerated SMVT.	I	B
In afrst-degree relative of a DCM/HNDCM patient, an ECG, and an echocardiogram are recommended if: • the index patient was diagnosed,50 years of age or has clinical features suggestive of an inherited cause, or • there is family history of DCM/HNDCM, or premature unexpected SD.	I	C
Recommendations for diagnostic, risk stratifcation, sudden cardiac death prevention and treatment of ventricular arrhythmia in arrhythmogenic right ventricular cardiomyopathy
In patients with suspected ARVC, CMR is recommended.	I	B
In patients with a suspected or defnite diagnosis of ARVC, genetic counselling and testing are recommended.	I	B
Avoidance of high-intensity exercise is recommended in patients with a defnite diagnosis of ARVC.	I	B
ICD implantation is recommended in ARVC patients with haemodynamically not-tolerated VT or VF.	I	C
In patients with ARVC and non-sustained or sustained VAs, beta-blocker therapy is recommended.	I	C
In afrst-degree relative of a patient with ARVC, ECG, and echocardiogram are recommended.	I	C
Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in hypertrophic cardiomyopathy
CMR with LGE is recommended in HCM patients for diagnostic work-up.	I	B
Genetic counselling and testing are recommended in HCM patients.	I	B
It is recommended that the 5-year risk of SCD is assessed atfrst evaluation and at 1–3-year intervals or when there is a change in clinical status.	I	C
ICD implantation is recommended in HCM patients with haemodynamically not-tolerated VT or VF.	I	B
In afrst-degree relative of a patient with HCM, ECG, and echocardiogram are recommended.	I	C
Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in neuromuscular diseases
Annual follow-up with at least a 12-lead ECG is recommended in patients with muscular dystrophies, even in the concealed phase of the disease.	I	C
It is recommended that patients with neuromuscular disorders who have VAs or ventricular dysfunction are treated in the same way for arrhythmia as patients without neuromuscular disorders.	I	C
Invasive electrophysiological evaluation is recommended in patients with myotonic dystrophy and palpitations or syncope suggestive of VA, VT, or surviving a CA.	I	C
ICD implantation is recommended in patients with myotonic dystrophy and SMVT or aborted CA not caused by BBR-VT.	I	C
In myotonic dystrophy patients, serial electrophysiological evaluation of AV conduction and arrhythmia induction is not recommended without arrhythmia suspicion or progression of ECG conduction disorders.	III	C
In symptomatic patients with BBR-VT, catheter ablation is recommended.	I	C
In patients with myotonic dystrophy undergoing ablation for BBR-VT, pacemaker/ICD implantation is recommended.	I	C

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Recommendations for sudden cardiac death prevention, and treatment of ventricular arrhythmia in myocarditis	Recommendations for sudden cardiac death prevention, and treatment of ventricular arrhythmia in myocarditis
In confrmed or clinically suspected acute myocarditis, it is recommended that patients who present with life-threatening VA are referred to a specialized centre.	I	C
In patients with haemodynamically not-tolerated SMVT occurring in the chronic phase of myocarditis, an ICD implantation is recommended.	I	C
Recommendations for risk stratifcation, sudden cardiac death prevention, and treatment of ventricular arrhythmia in cardiac sarcoidosis
ICD implantation is recommended in patients with cardiac sarcoidosis who have an LVEF≤35%.	I	B
ICD implantation is recommended in patients with cardiac sarcoidosis who (a) have documented sustained VT, or (2) aborted CA.	I	B
Recommendations for sudden cardiac death prevention, and treatment of ventricular arrhythmia in valvular heart disease
PES with standby catheter ablation is recommended in patients with aortic valve disease and SMVT to identify and ablate BBR-VT, especially if it occurs following a valve intervention.	I	C
In patients with valvular heart disease and persistent LV dysfunction after surgical correction (if possible) it is recommended that ICD implantation for primary prevention follows DCM/HNDCM recommendations.	I	C
Recommendations for sudden cardiac death prevention, and treatment of ventricular arrhythmia in congenital heart disease
In adults with CHD with biventricular physiology and a left systemic ventricle presenting with symptomatic heart failure (NYHA II/III) and EF≤35% despite≥3 months of OMT, ICD implantation is indicated.	I	C
In patients with CHD presenting with sustained VAs, evaluation for residual or new anatomical abnormalities is recommended.	I	B
In patients with CHD with not-tolerated VT/aborted CA due to VF, ICD implantation is indicated after exclusion of reversible causes.	I	C
In patients with repaired TOF who present with SMVT or recurrent, symptomatic appropriate ICD therapy for SMVT, catheter ablation performed in specialized centres is recommended.	I	C
Recommendations for management of patients with idiopathic ventricularfbrillation
It is recommended that idiopathic VF is diagnosed in a SCA survivor, preferably with documentation of VF, after exclusion of an underlying structural, channelopathic, metabolic, or toxicological aetiology.	I	B
ICD implantation is recommended in idiopathic VF.	I	B
Recommendations for management of patients with long QT syndrome
It is recommended that LQTS is diagnosed with either QTc≥480 ms in repeated 12-lead ECGs with or without symptoms or LQTS diagnostic score.3.	I	C
In patients with clinically diagnosed long QT syndrome, genetic testing, and genetic counselling are recommended.	I	C
It is recommended that LQTS is diagnosed in the presence of a pathogenic mutation, irrespective of the QT duration.	I	C
Routine diagnostic testing with epinephrine challenge is not recommended in LQTS.	III	C
The following is recommended in LQTS: • Avoid QT-prolonging drugs.f • Avoid and correct electrolyte abnormalities. • Avoid genotype-specifc triggers for arrhythmias.	I	C
Beta-blockers, ideally non-selective beta-blockers (nadolol or propranolol), are recommended in LQTS patients with documented QT interval prolongation, to reduce risk of arrhythmic events.	I	B
Mexiletine is indicated in LQT3 patients with a prolonged QT interval.	I	C
ICD implantation in addition to beta-blockers is recommended in LQTS patients with CA.	I	B
ICD implantation is recommended in patients with LQTS who are symptomaticg while receiving beta-blockers and genotype-specifc therapies.	I	C

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LCSD is indicated in patients with symptomaticg LQTS when: (a) ICD therapy is contraindicated or declined; (b) patient is on beta-blockers and genotype-specifc therapies with an ICD and experiences multiple shocks or syncope due to VA.	I	C
Invasive electrophysiologic study is not recommended in LQTS.	III	C
Recommendations for management of patients with Andersen–Tawil syndrome
Genetic testing is recommended in patients with suspected Andersen–Tawil syndrome.	I	C
ICD implantation is recommended in patients with Andersen–Tawil syndrome after aborted CA not tolerated sustained VT.	I	C
Recommendations for management of patients with Brugada syndrome
It is recommended that BrS is diagnosed in patients with no other heart disease and a spontaneous type 1 Brugada ECG pattern.	I	C
It is recommended that BrS is diagnosed in patients with no other heart disease who have survived a CA due to VF or PVT and exhibit a type 1 Brugada ECG inducedby sodium channel blocker challenge or during fever.	I	C
Genetic testing forSCN5Agene is recommended for probands with BrS.	I	C
Sodium channel blocker test is not recommended in patients with a prior type I Brugada pattern.	III	C
The following is recommended in all patients with BrS: (a) Avoidance of drugs that may induce ST-segment elevation in right precordial leads (http://www.brugadadrugs.org). (b) Avoidance of cocaine, cannabis, and excessive alcohol intake. (c) Treatment of fever with antipyretic drugs.	I	C
ICD implantation is recommended in patients with BrS who: (a) Are survivors of an aborted CA, and/or (b) Have documented spontaneous sustained VT.	I	C
Catheter ablation in asymptomatic BrS patients is not recommended.	III	C
Recommendations for management of patients with early repolarizaton pattern/syndrome
It is recommended that the ERP is diagnosed as J-point elevation of≥1 mm in two adjacent inferior and/or lateral ECG leads.	I	C
It is recommended that the ERS is diagnosed in a patient resuscitated from unexplained VF/PVT in the presence of ERP.	I	C
Clinical evaluation is not recommended routinely in asymptomatic subjects with ERP.	III	C
ICD implantation is recommended in patients with a diagnosis of ERS who have survived a CA.	I	B
ICD implantation is not recommended in asymptomatic patients with an isolated ERP.	III	C
Recommendations for management of patients with catecholaminergic polymorphic ventricular tachycardia
It is recommended that CPVT is diagnosed in the presence of a structurally normal heart, normal ECG, and exercise- or emotion-induced bidirectional or PVT.	I	C
It is recommended that CPVT is diagnosed in patients who are carriers of a mutation in disease-causing genes.	I	C
Genetic testing and genetic counselling are indicated in patients with clinical suspicion or clinical diagnosis of CPVT.	I	C
Avoidance of competitive sports, strenuous exercise, and exposure to stressful environments is recommended in all patients with CPVT.	I	C
Beta-blockers, ideally non-selective (nadolol or propranolol), are recommended in all patients with a clinical diagnosis of CPVT.	I	C
ICD implantation combined with beta-blockers andfecainide is recommended in CPVT patients after aborted CA.	I	C
PES is not recommended for stratifcation of SCD risk.	III	C

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Recommendations for management of patients with short QT syndrome
It is recommended that SQTS is diagnosed in the presence of a QTc≤360 ms and one or more of the following: (a) a pathogenic		I		C
mutation, (b) a family history of SQTS, (c) survival from a VT/VF episode in the absence of heart disease.
Genetic testing is indicated in patients diagnosed with SQTS.		I		C
ICD implantation is recommended in patients with a diagnosis of SQTS who: (a) are survivors of an aborted CA, and/or (b) have		I		C
documented spontaneous sustained VT.
PES is not recommended for SCD risk stratifcation in SQTS patients. Recommendations for the prevention of sudden cardiac death and management of ventricular arrhythmia during During pregnancy, electrical cardioversion is recommended for sustained VT. If ICD implantation is indicated during pregnancy, implantation is recommended with optimal radiation protection. Continuation of beta-blockers is recommended during pregnancy and post-partum in patients with LQTS or CPVT. Recommendations for risk stratifcation and prevention of sudden cardiac death in athletes In athletes with positive medical history, abnormal physical examination, or ECG alterations, further investigations including echocardiography and/or CMR to confrm (or exclude) an underlying disease are recommended. It is recommended that athletes diagnosed with a cardiovascular disease associated with SCD are managed according to current guidelines for sports eligibility. It is recommended that staff at sporting facilities are trained in CPR and in the use of AED.		III pregnancy I I I I I I		C C C C C C C	© ESC 2022

AAD, anti-arrhythmic drug; ACE-I, angiotensin-converting-enzyme inhibitor; AED, automated external defibrillator; ARB, angiotensin receptor blockers; ARNIs, angiotensin receptor neprilysin inhibitor; ARVC, arrhythmogenic right ventricular cardiomyopathy; ATP, anti-tachycardia pacing; AV, atrioventricular; BBR-VT, bundle branch re-entry; BrS, Brugada syndrome; CA, cardiac arrest; CAD, coronary artery disease; CCB, calcium channel blocker; CHD, congenital heart disease; CIED, cardiac implantable electronic devices; CMR, cardiac magnetic resonance; CPR, cardiopulmonary resuscitation; CPVT, catecholaminergic polymorphic ventricular tachycardia; CRT, cardiac resynchronization therapy; DC, direct current; DCM, dilated cardiomyopathy; ECG, electrocardiogram; EF, ejection fraction; ERP, early repolarization pattern; ERS, early repolarization syndrome; HCM, hypertrophic cardiomyopathy; HNDCM, hypokinetic non-dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; CAD, coronary artery disease; ILR, implantable loop recorder; LCSD, left cardiac sympathetic denervation; LGE, late gadolinium enhancement; LQTS, long QT syndrome; LV, left ventricular; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; OHCA, out-of-hospital cardiac arrest; OMT, optimal medical therapy; PES, programmed electrical stimulation; PVC, premature ventricular complex; PVT, polymorphic ventricular tachycardia; RVOT, right ventricular outflow tract; SADS, sudden arrhythmic death syndrome; SCA, sudden cardiac arrest; SCD, sudden cardiac death; SD, sudden death; SGLT2, sodium–glucose co-transporter 2; SHD, structural heart disease; SMVT, sustained monomorphic ventricular tachycardia; SQT, short QT syndrome; STEMI, ST-elevation myocardial infarction; SVT, supraventricular tachycardia; VA, ventricular arrhythmia; VF, ventricular fibrillation; VT, ventricular tachycardia. aClass of recommendation. bLevel of evidence. cShopping malls, stadiums, public transport stations, casinos. dList not exhaustive. eLOE C for VT/PVCs from left fascicles. fhttp://www.crediblemeds.org gArrhythmic syncope or haemodynamically non-tolerated VA

12. Quality indicators

Quality indicators (QIs) are tools that may be used to evaluate care quality, including structural aspects, process, and outcomes of care. They serve as a mechanism for enhancing adherence to guideline recommendations, through associated quality improvement initiatives and the benchmarking of care providers. As such, the role of QIs in improving care and outcomes is increasingly recognized by healthcare authorities, professional organizations, payers, and the public.

The ESC understands the need for measuring and reporting quality and outcomes of cardiovascular care, and has established methods for the development of the ESC QIs for the quantification of care and outcomes for cardiovascular disease. In parallel with the writing of this Clinical Practice Guideline document, a process has been initiated to develop QIs for patients with, or at risk of, VA or SCD using the ESC methodology and through the collaboration with domain experts and the European Heart Rhythm

Association. These QIs, alongside their specifications and development process, will be published separately.

13. Supplementary data

Supplementary data is available at European Heart Journal online.

14. Data availability statement

No new data were generated or analysed in support of this research.

15. Author information

Author/task force Member Af liations:

Marta de Riva, Cardiology, Leiden University Medical Centre, Leiden, Netherlands; Bo Gregers Winkel, Cardiology,

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Rigshospitalet, Copenhagen, Denmark, European Reference Networks for rare, low prevalence and complex diseases of the heart, ERN-GUARD HEART; Elijah R. Behr, Cardiovascular Clinical Academic Group, Cardiology Section, St George’s, University of London, London, United Kingdom, Department of Cardiology, St George’s University Hospitals NHS Foundation Trust, London, United Kingdom, and Cardiology, Mayo Clinic Healthcare, London, United Kingdom; Nico A. Blom, Paediatric Cardiology, Leiden University Medical Centre, Leiden, Netherlands, and Paediatric Cardiology, Amsterdam University Medical Center, Amsterdam, Netherlands; Philippe Charron, APHP, Centre de Référence des Maladies Cardiaques Héréditaires ou Rares, Hôpital Pitié-Salpêtrière, Paris, France, UMR_S 1166, and ICAN Institute for Cardiometabolism, and Nutrition, Sorbonne Université, Paris, France, and European Reference Networks for rare, low prevalence and complex diseases of the heart, ERN-Guard HEART, Paris, France; Domenico Corrado, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padova, Italy; Nikolaos Dagres, Department of Electrophysiology, Heart Center Leipzig at University of Leipzig, Leipzig, Germany; Christian de Chillou, Department of Cardiology, CHRU-Nancy, Nancy, France, and IADI, INSERM U1254, Université de Lorraine, Nancy, France; Lars Eckardt, Department of Cardiology II—Electrophysiology, University Hospital Münster, Münster, Germany; Tim Friede, Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany, and Partner Site Goettingen, DZHK (German Center for Cardiovascular Research), Goettingen, Germany; Kristina H. Haugaa, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway, and Faculty of Medicine, University of Oslo, Oslo, Norway; Mélèze Hocini, Cardiology Department, Liryc Institute, Pessac, France, Hopital Cardiologique du Haut Lévêque, Pessac, France, and Université de Bordeaux, Bordeaux, France; Pier D. Lambiase, Institute of Cardiovascular Science, University College, London, United Kingdom, Barts Heart Centre, St Bartholomews Hospital, London, United Kingdom, and Heart, Vascular and Thoracic Institute, Cleveland Clinic, London, United Kingdom; Eloi Marijon, Cardiology Department, European Georges Pompidou Hospital, Paris, France; Jose L. Merino, Arrhythmia and Electrophysiology Robotic Unit, La Paz University Hospital, Universidad Autonoma, IdiPaz, Madrid, Spain, Cardiology Department, Hospital Ruber Juan Bravo, Madrid, Spain, and Cardiac Electrophysiology, Hospital Viamed Santa Elena, Madrid, Spain; Petr Peichl, Cardiology Department, IKEM, Prague, Czech Republic; Silvia G. Priori, Molecular Medicine Department, University of Pavia, Pavia, Italy, Molecular Cardiology Department, Istituti Clinici Scientifici Maugeri SpA SB, Pavia, Italy, and Molecular Cardiology Department, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain, European Reference Networks for rare, low prevalence and complex diseases of the heart, ERNGUARD HEART; Tobias Reichlin, Department of Cardiology, Inselspital—University Hospital Bern, University of Bern, Bern, Switzerland; Jeanette Schulz-Menger, Cardiology, ECRC, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany, Cardiology, Helios Clinics Berlin-Buch, Berlin, Germany,

and DZHK Partnersite Berlin, Charité, Berlin, Germany; Christian Sticherling, Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland; Stylianos Tzeis, Cardiology Department, Mitera Hospital, Hygeia Group, Athens, Greece; Axel Verstrael (Belgium), ESC Patient Forum, Sophia Antipolis, France; and Maurizio Volterrani, Department of Cardiology, IRCCS San Raffaele Roma, Rome, Italy, and Professor of Exercise Science and Medicine, San Raffaele Telematic University of Rome, Rome.

16. Appendix

ESC Scientific Document Group

Includes Document Reviewers and ESC National Cardiac Societies.

Document Reviewers: Maja Cikes (CPG Review Coordinator) (Croatia), Paulus Kirchhof (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Elena Arbelo (Spain), Fernando Arribas (Spain), Riccardo Asteggiano (Italy), Cristina Basso (Italy), Axel Bauer (Austria), Emanuele Bertaglia (Italy), Tor Biering-Sørensen (Denmark), Carina Blomström-Lundqvist (Sweden), Michael A. Borger (Germany), Jelena Čelutkienė (Lithuania), Bernard Cosyns (Belgium), Volkmar Falk (Germany), Laurent Fauchier (France), Bulent Gorenek (Turkey), Sigrun Halvorsen (Norway), Robert Hatala (Slovakia), Hein Heidbuchel (Belgium), Stefan Kaab (Germany), Aleksandra Konradi (Russian Federation), Konstantinos C. Koskinas (Switzerland), Dipak Kotecha (United Kingdom), Ulf Landmesser (Germany), Basil S. Lewis (Israel), Ales Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Andreas Metzner (Germany), Richard Mindham (United Kingdom), Jens Cosedis Nielsen (Denmark), Tone M. Norekvål (Norway), Monica Patten (Germany), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Carol Ann Remme (Netherlands), Ivo Roca-Luque (Spain), Andrea Sarkozy (Belgium), Daniel Scherr (Austria), Marta Sitges (Spain), Rhian M. Touyz (Canada/United Kingdom), Nicolas Van Mieghem (Netherlands), Vedran Velagic (Croatia), Sami Viskin (Israel), and Paul G. A. Volders (Netherlands).

ESC National Cardiac Societies actively involved in the review process of the 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death.

Algeria: Algerian Society of Cardiology, Brahim Kichou; Armenia: Armenian Cardiologists Association, Mihran Martirosyan; Austria: Austrian Society of Cardiology, Daniel Scherr; Azerbaijan: Azerbaijan Society of Cardiology, Farid Aliyev; Belgium: Belgian Society of Cardiology, Rik Willems; Bosnia and Herzegovina: Association of Cardiologists of Bosnia and Herzegovina, Nabil Naser; Bulgaria: Bulgarian Society of Cardiology, Tchavdar Shalganov; Croatia: Croatian Cardiac Society, Davor Milicic; Cyprus: Cyprus Society of Cardiology, Theodoros Christophides; Czech Republic: Czech Society of Cardiology, Josef Kautzner; Denmark: Danish Society of Cardiology, Jim Hansen; Egypt: Egyptian Society of Cardiology, Lamyaa Allam; Estonia: Estonian Society of Cardiology, Priit Kampus; Finland: Finnish Cardiac Society, Juhani Junttila; France: French Society of Cardiology, Christophe Leclercq; Georgia: Georgian Society of Cardiology, Kakhaber Etsadashvili; Germany: German Cardiac Society, Daniel Steven; Greece: Hellenic Society of Cardiology, Konstantinos Gatzoulis; Hungary:

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Hungarian Society of Cardiology, László Gellér; Iceland: Icelandic Society of Cardiology, David O. Arnar; Ireland: Irish Cardiac Society, Joseph Galvin, European Reference Networks for rare, low prevalence and complex diseases of the heart, ERN-GUARD HEART; Israel: Israel Heart Society, Moti Haim; Italy: Italian Federation of Cardiology, Carlo Pappone; Kosovo (Republic of): Kosovo Society of Cardiology, Shpend Elezi; Kyrgyzstan: Kyrgyz Society of Cardiology, Alina Kerimkulova; Latvia: Latvian Society of Cardiology, Oskars Kalejs; Lebanon: Lebanese Society of Cardiology, Ali Rabah; Lithuania: Lithuanian Society of Cardiology, Aras Puodziukynas; Luxembourg: Luxembourg Society of Cardiology, Carlo Dimmer; Malta: Maltese Cardiac Society, Mark Adrian Sammut; Moldova (Republic of): Moldavian Society of Cardiology, Lilia David; Montenegro: Montenegro Society of Cardiology, Aneta Boskovic; Morocco: Moroccan Society of Cardiology, Abdelhamid Moustaghfir; Netherlands: Netherlands Society of Cardiology, Alexander H. Maass; North Macedonia: North Macedonian Society of Cardiology, Lidija Poposka; Norway: Norwegian Society of Cardiology, Ole Christian Mjolstad; Poland: Polish Cardiac Society, Przemysław Mitkowski; Portugal: Portuguese Society of Cardiology, Leonor Parreira; Romania: Romanian Society of Cardiology, Dragos Cozma; Russian Federation: Russian Society of Cardiology, Elena Golukhova; San Marino: San Marino Society of Cardiology, Roberto Bini; Serbia: Cardiology Society of Serbia, Sinisa Stojkovic; Slovakia: Slovak Society of Cardiology, Peter Hlivak; Slovenia: Slovenian Society of Cardiology, Andrej Pernat; Spain: Spanish Society of Cardiology, Nicasio Perez Castellano; Sweden: Swedish Society of Cardiology, Pyotr G. Platonov; Switzerland: Swiss Society of Cardiology, Firat Duru; Syrian Arab Republic: Syrian Cardiovascular Association, Ahmad Rasheed Al Saadi; Tunisia: Tunisian Society of Cardiology and Cardio-Vascular Surgery, Sana Ouali; Turkey: Turkish Society of Cardiology, Sabri Demircan; Ukraine: Ukrainian Association of Cardiology, Oleg Sychov; and United Kingdom of Great Britain and Northern Ireland: British Cardiovascular Society, Alistair Slade.

ESC Clinical Practice Guidelines (CPG) Committee: Colin Baigent (Chairperson) (United Kingdom), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Sotiris Antoniou (United Kingdom), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Andreas Baumbach (United Kingdom), Michael A. Borger (Germany), Jelena Čelutkienė (Lithuania), Maja Cikes (Croatia), Jean-Philippe Collet (France), Volkmar Falk (Germany), Laurent Fauchier (France), Chris P. Gale (United Kingdom), Sigrun Halvorsen (Norway), Bernard Iung (France), Tiny Jaarsma (Sweden), Aleksandra Konradi (Russian Federation), Konstantinos C. Koskinas (Switzerland), Dipak Kotecha (United Kingdom), Ulf Landmesser (Germany), Basil S. Lewis (Israel), Ales Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Richard Mindham (United Kingdom), Jens Cosedis Nielsen (Denmark), Steffen E. Petersen (United Kingdom), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Marta Sitges (Spain), and Rhian M. Touyz (Canada/United Kingdom).

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72. Aro AL, Reinier K, Rusinaru C, Uy-Evanado A, Darouian N, Phan D, et al. Electrical risk score beyond the left ventricular ejection fraction: prediction of sudden cardiac death in the Oregon Sudden Unexpected Death Study and the Atherosclerosis Risk in Communities Study. Eur Heart J 2017;38:3017–3025.

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75. Yoshinaga M, Kucho Y, Sarantuya J, Ninomiya Y, Horigome H, Ushinohama H, et al. Genetic characteristics of children and adolescents with long-QT syndrome diagnosed by school-based electrocardiographic screening programs. Circ Arrhythm Electrophysiol 2014;7:107–112.

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78. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778–1785.

79. Barsheshet A, Goldenberg I, O-Uchi J, Moss AJ, Jons C, Shimizu W, et al. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. Circulation 2012;125:1988–1996.

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84. Norrish G, Ding T, Field E, Ziólkowska L, Olivotto I, Limongelli G, et al. Development of a novel risk prediction model for sudden cardiac death in childhood hypertrophic cardiomyopathy (HCM risk-kids). JAMA Cardiol 2019;4: 918–927.

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106. Ranthe MF, Winkel BG, Andersen EW, Risgaard B, Wohlfahrt J, Bundgaard H, et al. Risk of cardiovascular disease in family members of young sudden cardiac death victims. Eur Heart J 2013;34:503–511.

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116. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Eur Heart J 2010;31:806–814.

117. Giudicessi JR, Ackerman MJ. Exercise testing oversights underlie missed and delayed diagnosis of catecholaminergic polymorphic ventricular tachycardia in young sudden cardiac arrest survivors. Heart Rhythm 2019;16:1232–1239.

118. Roston TM, Kallas D, Davies B, Franciosi S, De Souza AM, Laksman ZW, et al. Burst exercise testing can unmask arrhythmias in patients with incompletely penetrant catecholaminergic polymorphic ventricular tachycardia. JACC Clin Electrophysiol 2021;7:437–441.

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119. Sy RW, van der Werf C, Chattha IS, Chockalingam P, Adler A, Healey JS, et al. Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. Circulation 2011;124:2187–2194.

120. Binder T. Transthoracic echocardiography and the standard examination of specific cardiac structures. ESC CardioMed. 3rd ed. Oxford University Press; 2022. p425–431.

121. Haugaa KH, Basso C, Badano LP, Bucciarelli-Ducci C, Cardim N, Gaemperli O, et al. Comprehensive multi-modality imaging approach in arrhythmogenic cardiomyopathy—an expert consensus document of the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2017;18:237–253.

122. Haugaa KH, Grenne BL, Eek CH, Ersboll M, Valeur N, Svendsen JH, et al. Strain echocardiography improves risk prediction of ventricular arrhythmias after myocardial infarction. JACC Cardiovasc Imaging 2013;6:841–850.

123. Haugaa KH, Hasselberg NE, Edvardsen T. Mechanical dispersion by strain echocardiography: a predictor of ventricular arrhythmias in subjects with lamin A/C mutations. JACC Cardiovasc Imaging 2015;8:104–106.

124. Ersboll M, Valeur N, Andersen MJ, Mogensen UM, Vinther M, Svendsen JH, et al. Early echocardiographic deformation analysis for the prediction of sudden cardiac death and life-threatening arrhythmias after myocardial infarction. JACC Cardiovasc Imaging 2013;6:851–860.

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126. Garg R, Friedrich MG. Cardiomyopathies. ESC CardioMed. 3rd ed. Oxford University Press; 2022, p510–515.

127. Borgquist R, Haugaa KH, Gilljam T, Bundgaard H, Hansen J, Eschen O, et al. The diagnostic performance of imaging methods in ARVC using the 2010 task force criteria. Eur Heart J Cardiovasc Imaging 2014;15:1219–1225.

128. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35:2733–2779.

129. Di Marco A, Anguera I, Schmitt M, Klem I, Neilan TG, White JA, et al. Late gadolinium enhancement and the risk for ventricular arrhythmias or sudden death in dilated cardiomyopathy: systematic review and meta-analysis. JACC Heart Fail 2017;5: 28–38.

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132. Achenbach S. Technology of cardiac computed tomography. ESC CardioMed. 3rd ed. Oxford University Press; 2022, p537–541.

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135. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Europace 2013;15: 1389–1406.

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137. Churet M, Luttoo K, Hocini M, Haïssaguerre M, Sacher F, Duchateau J. Diagnostic reproducibility of epinephrine drug challenge interpretation in suspected long QT syndrome. J Cardiovasc Electrophysiol 2019;30:896–901.

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147. Gatzoulis KA, Vouliotis A-I, Tsiachris D, Salourou M, Archontakis S, Dilaveris P, et al. Primary prevention of sudden cardiac death in a nonischemic dilated cardiomyopathy population: reappraisal of the role of programmed ventricular stimulation. Circ Arrhythm Electrophysiol 2013;6:504–512.

148. Brilakis ES, Shen WK, Hammill SC, Hodge DO, Rea RF, Lexvold NY, et al. Role of programmed ventricular stimulation and implantable cardioverter defibrillators in patients with idiopathic dilated cardiomyopathy and syncope. Pacing Clin Electrophysiol 2001;24:1623–1630.

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157. Lazarus A, Varin J, Babuty D, Anselme F, Coste J, Duboc D. Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study. J Am Coll Cardiol 2002;40:1645–1652.

158. Tandri H, Asimaki A, Abraham T, Dalal D, Tops L, Jain R, et al. Prolonged RV endocardial activation duration: a novel marker of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Heart Rhythm 2009;6:769–775.

159. Gomes J, Finlay M, Ahmed AK, Ciaccio EJ, Asimaki A, Saffitz JE, et al. Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study. Eur Heart J 2012;33:1942–1953.

160. Orini M, Graham AJ, Srinivasan NT, Campos FO, Hanson BM, Chow A, et al. Evaluation of the reentry vulnerability index to predict ventricular tachycardia circuits using high-density contact mapping. Heart Rhythm 2020;17:576–583.

161. Jackson N, Gizurarson S, Viswanathan K, King B, Massé S, Kusha M, et al. Decrement evoked potential mapping: basis of a mechanistic strategy for ventricular tachycardia ablation. Circ Arrhythm Electrophysiol 2015;8:1433–1442.

162. Avella A, d’Amati G, Pappalardo A, Re F, Silenzi PF, Laurenzi F, et al. Diagnostic value of endomyocardial biopsy guided by electroanatomic voltage mapping in arrhythmogenic right ventricular cardiomyopathy/dysplasia. J Cardiovasc Electrophysiol 2008;19:1127–1134.

163. Wilde AAM, Behr ER. Genetic testing for inherited cardiac disease. Nat Rev Cardiol 2013;10:571–583.

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165. Ingles J, Goldstein J, Thaxton C, Caleshu C, Corty EW, Crowley SB, et al. Evaluating the clinical validity of hypertrophic cardiomyopathy genes. Circ Genom Precis Med 2019;12:e002460.

166. Adler A, Novelli V, Amin AS, Abiusi E, Care M, Nannenberg EA, et al. An international, multicentered, evidence-based reappraisal of genes reported to cause congenital long QT syndrome. Circulation 2020;141:418–428.

167. Risgaard B, Jabbari R, Refsgaard L, Holst AG, Haunsø S, Sadjadieh A, et al. High prevalence of genetic variants previously associated with Brugada syndrome in new exome data. Clin Genet 2013;84:489–495.

168. James CA, Jongbloed JDH, Hershberger RE, Morales A, Judge DP, Syrris P, et al. An international evidence based reappraisal of genes associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) using the ClinGen framework. Circ Genom Precis Med 2021;14:e003273.

169. Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, et al. Transethnic genome-wide association study provides insights in the genetic architecture and heritability of long QT syndrome. Circulation 2020;142:324–338.

170. Wijeyeratne YD, Tanck MW, Mizusawa Y, Batchvarov V, Barc J, Crotti L, et al. SCN5A mutation type and a genetic risk score associate variably with Brugada syndrome phenotype in SCN5A families. Circ Genom Precis Med 2020;13:e002911.

171. Harper AR, Goel A, Grace C, Thomson KL, Petersen SE, Xu X, et al. Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. Nat Genet 2021;53:135–142.

172. Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, et al. Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect. Nat Genet 2021;53:128–134.

173. Tadros R, Tan HL, ESCAPE-NET Investigators, El Mathari S, Kors JA, Postema PG, et al. Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores. Eur Heart J 2019;40:3097–3107.

174. Ware JS, Roberts AM, Cook SA. Next generation sequencing for clinical diagnostics and personalised medicine: implications for the next generation cardiologist. Heart 2012;98:276–281.

175. Ashar FN, Mitchell RN, Albert CM, Newton-Cheh C, Brody JA, Müller-Nurasyid M, et al. A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. Eur Heart J 2018;39:3961–3969.

176. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–424.

177. Ingles J, Lind JM, Phongsavan P, Semsarian C. Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy. Genet Med 2008;10:117–120.

178. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Europace 2011;13:1077–1109.

179. Conte G, Wilde A, Behr ER, Scherr D, Lenarczyk R, Gandjbachkh E, et al. Importance of dedicated units for the management of patients with inherited arrhythmia syndromes. Circ Genom Precis Med 2021;14:e003313.

180. Minier M, Probst V, Berthome P, Tixier R, Briand J, Geoffroy O, et al. Age at diagnosis of Brugada syndrome: influence on clinical characteristics and risk of arrhythmia. Heart Rhythm 2020;17:743–749.

181. Wong LCH, Roses-Noguer F, Till JA, Behr ER. Cardiac evaluation of pediatric relatives in sudden arrhythmic death syndrome: a 2-center experience. Circ Arrhythm Electrophysiol 2014;7:800–806.

182. Mellor GJ, Blom LJ, Groeneveld SA, Winkel BG, Ensam B, Bargehr J, et al. Familial evaluation in idiopathic ventricular fibrillation: diagnostic yield and significance of J Wave Syndromes. Circ Arrhythm Electrophysiol 2021;14:e009089.

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397. Ploux S, Swerdlow CD, Strik M, Welte N, Klotz N, Ritter P, et al. Towards eradication of inappropriate therapies for ICD lead failure by combining comprehensive remote monitoring and lead noise alerts. J Cardiovasc Electrophysiol 2018;29: 1125–1134.

398. Ellenbogen KA, Gunderson BD, Stromberg KD, Swerdlow CD. Performance of Lead Integrity Alert to assist in the clinical diagnosis of implantable cardioverter defibrillator lead failures: analysis of different implantable cardioverter defibrillator leads. Circ Arrhythm Electrophysiol 2013;6:1169–1177.

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426. Galand V, Flécher E, Auffret V, Boulé S, Vincentelli A, Dambrin C, et al. Predictors and clinical impact of late ventricular arrhythmias in patients with continuous-flow left ventricular assist devices. JACC Clin Electrophysiol 2018;4:1166–1175.

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428. Clerkin KJ, Topkara VK, Demmer RT, Dizon JM, Yuzefpolskaya M, Fried JA, et al. Implantable cardioverter-defibrillators in patients with a continuous-flow left ventricular assist device: an analysis of the INTERMACS registry. JACC Heart Fail 2017; 5:916–926.

429. Oz MC, Rose EA, Slater J, Kuiper JJ, Catanese KA, Levin HR. Malignant ventricular arrhythmias are well tolerated in patients receiving long-term left ventricular assist devices. J Am Coll Cardiol 1994;24:1688–1691.

430. Potapov EV, Antonides C, Crespo-Leiro MG, Combes A, Färber G, Hannan MM, et al. 2019 EACTS Expert Consensus on long-term mechanical circulatory support. Eur J Cardiothorac Surg 56:230–270.

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431. Makki N, Mesubi O, Steyers C, Olshansky B, Abraham WT. Meta-analysis of the relation of ventricular arrhythmias to all-cause mortality after implantation of a left ventricular assist device. Am J Cardiol 2015;116:1385–1390.

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434. Brenyo A, Rao M, Koneru S, Hallinan W, Shah S, Massey HT, et al. Risk of mortality for ventricular arrhythmia in ambulatory LVAD patients. J Cardiovasc Electrophysiol 2012;23:515–520.

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436. Refaat MM, Tanaka T, Kormos RL, McNamara D, Teuteberg J, Winowich S, et al. Survival benefit of implantable cardioverter-defibrillators in left ventricular assist device-supported heart failure patients. J Card Fail 2012;18:140–145.

437. Cantillon DJ, Tarakji KG, Kumbhani DJ, Smedira NG, Starling RC, Wilkoff BL. Improved survival among ventricular assist device recipients with a concomitant implantable cardioverter-defibrillator. Heart Rhythm 2010;7:466–471.

438. Joyce E, Starling RC. HFrEF other treatment: ventricular assist devices. ESC CardioMed. 3rd ed. Oxford University Press; 2022, p1884–1889.

439. Younes A, Al-Kindi SG, Alajaji W, Mackall JA, Oliveira GH. Presence of implantable cardioverter-defibrillators and wait-list mortality of patients supported with left ventricular assist devices as bridge to heart transplantation. Int J Cardiol 2017; 231:211–215.

440. Agrawal S, Garg L, Nanda S, Sharma A, Bhatia N, Manda Y, et al. The role of implantable cardioverter-defibrillators in patients with continuous flow left ventricular assist devices – a meta-analysis. Int J Cardiol 2016;222:379–384.

441. Blomström-Lundqvist C, Traykov V, Erba PA, Burri H, Nielsen JC, Bongiorni MG, et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Europace 2020;22:515–549.

442. Burri H, Starck C, Auricchio A, Biffi M, Burri M, D’Avila A, et al. EHRA expert consensus statement and practical guide on optimal implantation technique for conventional pacemakers and implantable cardioverter-defibrillators: endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin-American Heart Rhythm Society (LAHRS). Europace 2021;23:983–1008.

443. Tarakji KG, Mittal S, Kennergren C, Corey R, Poole JE, Schloss E, et al. Antibacterial envelope to prevent cardiac implantable device infection. N Engl J Med 2019;380: 1895–1905.

444. Atti V, Turagam MK, Garg J, Koerber S, Angirekula A, Gopinathannair R, et al. Subclavian and axillary vein access versus cephalic vein cutdown for cardiac implantable electronic device implantation: a meta-analysis. JACC Clin Electrophysiol 2020;6: 661–671.

445. Benz AP, Vamos M, Erath JW, Hohnloser SH. Cephalic vs. subclavian lead implantation in cardiac implantable electronic devices: a systematic review and meta-analysis. Europace 2019;21:121–129.

446. Chan N-Y, Kwong N-P, Cheong A-P. Venous access and long-term pacemaker lead failure: comparing contrast-guided axillary vein puncture with subclavian puncture and cephalic cutdown. Europace 2017;19:1193–1197.

447. Defaye P, Boveda S, Klug D, Beganton F, Piot O, Narayanan K, et al. Dual- vs. singlechamber defibrillators for primary prevention of sudden cardiac death: long-term follow-up of the Défibrillateur Automatique Implantable-Prévention Primaire registry. Europace 2017;19:1478–1484.

448. Dewland TA, Pellegrini CN, Wang Y, Marcus GM, Keung E, Varosy PD. Dual-chamber implantable cardioverter-defibrillator selection is associated with increased complication rates and mortality among patients enrolled in the NCDR implantable cardioverter-defibrillator registry. J Am Coll Cardiol 2011;58:1007–1013.

449. Friedman PA, Bradley D, Koestler C, Slusser J, Hodge D, Bailey K, et al. A prospective randomized trial of single- or dual-chamber implantable cardioverterdefibrillators to minimize inappropriate shock risk in primary sudden cardiac death prevention. Europace 2014;16:1460–1468.

450. Chen B-W, Liu Q, Wang X, Dang A-M. Are dual-chamber implantable cardioverter-defibrillators really better than single-chamber ones? A systematic review and meta-analysis. J Interv Card Electrophysiol 2014;39:273–280.

451. Epstein LM, Love CJ, Wilkoff BL, Chung MK, Hackler JW, Bongiorni MG, et al. Superior vena cava defibrillator coils make transvenous lead extraction more challenging and riskier. J Am Coll Cardiol 2013;61:987–989.

452. Larsen JM, Hjortshøj SP, Nielsen JC, Johansen JB, Petersen HH, Haarbo J, et al. Single-coil and dual-coil defibrillator leads and association with clinical outcomes in a complete Danish nationwide ICD cohort. Heart Rhythm 2016;13:706–712.

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455. Stoevelaar R, Brinkman-Stoppelenburg A, Bhagwandien RE, van Bruchem-Visser RL, Theuns DA, van der Heide A, et al. The incidence and impact of implantable cardioverter defibrillator shocks in the last phase of life: an integrated review. Eur J Cardiovasc Nurs 2018;17:477–485.

456. Kapa S, Mueller PS, Hayes DL, Asirvatham SJ. Perspectives on withdrawing pacemaker and implantable cardioverter-defibrillator therapies at end of life: results of a survey of medical and legal professionals and patients. Mayo Clin Proc 2010; 85:981–990.

457. Padeletti L, Arnar DO, Boncinelli L, Brachman J, Camm JA, Daubert JC, et al. EHRA Expert Consensus Statement on the management of cardiovascular implantable electronic devices in patients nearing end of life or requesting withdrawal of therapy. Europace 2010;12:1480–1489.

458. Stoevelaar R, Brinkman-Stoppelenburg A, van Driel AG, Theuns DA, Bhagwandien RE, van Bruchem-Visser RL, et al. Trends in time in the management of the implantable cardioverter defibrillator in the last phase of life: a retrospective study of medical records. Eur J Cardiovasc Nurs 2019;18:449–457.

459. Kirkpatrick JN, Gottlieb M, Sehgal P, Patel R, Verdino RJ. Deactivation of implantable cardioverter defibrillators in terminal illness and end of life care. Am J Cardiol 2012;109:91–94.

460. Stevenson WG, Khan H, Sager P, Saxon LA, Middlekauff HR, Natterson PD, et al. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation 1993;88:1647–1670.

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463. Hsia HH, Callans DJ, Marchlinski FE. Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia. Circulation 2003;108:704–710.

464. Soejima K, Stevenson WG, Sapp JL, Selwyn AP, Couper G, Epstein LM. Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy. J Am Coll Cardiol 2004;43:1834–1842.

465. Miljoen H, State S, Dechillou C, Magninpoull I, Dotto P, Andronache M, et al. Electroanatomic mapping characteristics of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Europace 2005; 7:516–524.

466. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The task force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015;36: 2793–2867.

467. Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS Guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary. J Am Coll Cardiol 2018;72:1677–1749.

468. Towbin JA, McKenna WJ, Abrams DJ, Ackerman MJ, Calkins H, Darrieux FCC, et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: executive summary. Heart Rhythm 2019;16:e373–e407.

469. Moss AJ, Greenberg H, Case RB, Zareba W, Hall WJ, Brown MW, et al. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation 2004;110:3760–3765.

470. Poole JE, Johnson GW, Hellkamp AS, Anderson J, Callans DJ, Raitt MH, et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008;359:1009–1017.

471. Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin J-F, et al. Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med 2016; 375:111–121.

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472. Piccini JP, Berger JS, O’Connor CM. Amiodarone for the prevention of sudden cardiac death: a meta-analysis of randomized controlled trials. Eur Heart J 2009;30: 1245–1253.

473. Palaniswamy C, Kolte D, Harikrishnan P, Khera S, Aronow WS, Mujib M, et al. Catheter ablation of postinfarction ventricular tachycardia: ten-year trends in utilization, in-hospital complications, and in-hospital mortality in the United States. Heart Rhythm 2014;11:2056–2063.

474. Caceres J, Jazayeri M, McKinnie J, Avitall B, Denker ST, Tchou P, et al. Sustained bundle branch reentry as a mechanism of clinical tachycardia. Circulation 1989;79: 256–270.

475. Blanck Z, Dhala A, Deshpande S, Sra J, Jazayeri M, Akhtar M. Bundle branch reentrant ventricular tachycardia: cumulative experience in 48 patients. J Cardiovasc Electrophysiol 1993;4:253–262.

476. Chen H, Shi L, Yang B, Ju W, Zhang F, Yang G, et al. Electrophysiological characteristics of bundle branch reentry ventricular tachycardia in patients without structural heart disease. Circ Arrhythm Electrophysiol 2018;11:e006049.

477. Pathak RK, Fahed J, Santangeli P, Hyman MC, Liang JJ, Kubala M, et al. Long-term outcome of catheter ablation for treatment of bundle branch re-entrant tachycardia. JACC Clin Electrophysiol 2018;4:331–338.

478. Stevenson WG, Wilber DJ, Natale A, Jackman WM, Marchlinski FE, Talbert T, et al. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation 2008;118:2773–2782.

479. Della Bella P, Baratto F, Tsiachris D, Trevisi N, Vergara P, Bisceglia C, et al. Management of ventricular tachycardia in the setting of a dedicated unit for the treatment of complex ventricular arrhythmias: long-term outcome after ablation. Circulation 2013;127:1359–1368.

480. Maury P, Baratto F, Zeppenfeld K, Klein G, Delacretaz E, Sacher F, et al. Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%. Eur Heart J 2014;35:1479–1485.

481. Tung R, Vaseghi M, Frankel DS, Vergara P, Di Biase L, Nagashima K, et al. Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: an International VT Ablation Center Collaborative Group study. Heart Rhythm 2015;12:1997–2007.

482. Santangeli P, Zado ES, Supple GE, Haqqani HM, Garcia FC, Tschabrunn CM, et al. Long-term outcome with catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2015;8:1413–1421.

483. Marchlinski FE, Haffajee CI, Beshai JF, Dickfeld T-ML, Gonzalez MD, Hsia HH, et al. Long-term success of irrigated radiofrequency catheter ablation of sustained ventricular tachycardia. J Am Coll Cardiol 2016;67:674–683.

484. Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, et al. Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med 2007;357:2657–2665.

485. Kuck K-H, Schaumann A, Eckardt L, Willems S, Ventura R, Delacrétaz E, et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. Lancet 2010;375:31–40.

486. Anter E, Kleber AG, Rottmann M, Leshem E, Barkagan M, Tschabrunn CM, et al. Infarct-related ventricular tachycardia. JACC Clin Electrophysiol 2018;4:1033–1048.

487. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation 2000;101:1288–1296.

488. de Chillou C, Groben L, Magnin-Poull I, Andronache M, Abbas MM, Zhang N, et al. Localizing the critical isthmus of postinfarct ventricular tachycardia: the value of pace-mapping during sinus rhythm. Heart Rhythm 2014;11:175–181.

489. Jaïs P, Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, et al. Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia. Circulation 2012;125:2184–2196.

490. Berruezo A, Fernandez-Armenta J. Lines, circles, channels, and clouds: looking for the best design for substrate-guided ablation of ventricular tachycardia. Europace 2014;16:943–945.

491. Di Biase L, Burkhardt JD, Lakkireddy D, Carbucicchio C, Mohanty S, Mohanty P, et al. Ablation of stable VTs versus substrate ablation in ischemic cardiomyopathy. J Am Coll Cardiol 2015;66:2872–2882.

492. Berruezo A, Fernández-Armenta J, Andreu D, Penela D, Herczku C, Evertz R, et al. Scar dechanneling: new method for scar-related left ventricular tachycardia substrate ablation. Circ Arrhythm Electrophysiol 2015;8:326–336.

493. Haïssaguerre M, Shoda M, Jaïs P, Nogami A, Shah DC, Kautzner J, et al. Mapping and ablation of idiopathic ventricular fibrillation. Circulation 2002;106:962–967.

494. Shirai Y, Liang JJ, Santangeli P, Arkles JS, Schaller RD, Supple GE, et al. Comparison of the ventricular tachycardia circuit between patients with ischemic and nonischemic cardiomyopathies: detailed characterization by entrainment. Circ Arrhythm Electrophysiol 2019;12:e007249.

495. Bhaskaran A, Tung R, Stevenson WG, Kumar S. Catheter ablation of VT in nonischaemic cardiomyopathies: endocardial, epicardial and intramural approaches. Heart Lung Circ 2019;28:84–101.

496. Tung R, Raiman M, Liao H, Zhan X, Chung FP, Nagel R, et al. Simultaneous endocardial and epicardial delineation of 3D reentrant ventricular tachycardia. J Am Coll Cardiol 2020;75:884–897.

497. Dinov B, Fiedler L, Schönbauer R, Bollmann A, Rolf S, Piorkowski C, et al. Outcomes in catheter ablation of ventricular tachycardia in dilated nonischemic cardiomyopathy compared with ischemic cardiomyopathy: results from the Prospective Heart Centre of Leipzig VT (HELP-VT) Study. Circulation 2014;129: 728–736.

498. Proietti R, Essebag V, Beardsall J, Hache P, Pantano A, Wulffhart Z, et al. Substrate-guided ablation of haemodynamically tolerated and untolerated ventricular tachycardia in patients with structural heart disease: effect of cardiomyopathy type and acute success on long-term outcome. Europace 2015;17:461–467.

499. Ebert M, Richter S, Dinov B, Zeppenfeld K, Hindricks G. Evaluation and management of ventricular tachycardia in patients with dilated cardiomyopathy. Heart Rhythm 2019;16:624–631.

500. Proietti R, Lichelli L, Lellouche N, Dhanjal T. The challenge of optimising ablation lesions in catheter ablation of ventricular tachycardia. J Arrhythmia 2021;37: 140–147.

501. Tokuda M, Sobieszczyk P, Eisenhauer AC, Kojodjojo P, Inada K, Koplan BA, et al. Transcoronary ethanol ablation for recurrent ventricular tachycardia after failed catheter ablation: an update. Circ Arrhythm Electrophysiol 2011;4:889–896.

502. Kreidieh B, Rodríguez-Mañero M, Schurmann P, Ibarra-Cortez SH, Dave AS, Valderrábano M. Retrograde coronary venous ethanol infusion for ablation of refractory ventricular tachycardia. Circ Arrhythm Electrophysiol 2016;9:e004352.

503. Nguyen DT, Tzou WS, Sandhu A, Gianni C, Anter E, Tung R, et al. Prospective multicenter experience with cooled radiofrequency ablation using high impedance irrigant to target deep myocardial substrate refractory to standard ablation. JACC Clin Electrophysiol 2018;4:1176–1185.

504. Stevenson WG, Tedrow UB, Reddy V, AbdelWahab A, Dukkipati S, John RM, et al. Infusion needle radiofrequency ablation for treatment of refractory ventricular arrhythmias. J Am Coll Cardiol 2019;73:1413–1425.

505. Igarashi M, Nogami A, Fukamizu S, Sekiguchi Y, Nitta J, Sakamoto N, et al. Acute and long-term results of bipolar radiofrequency catheter ablation of refractory ventricular arrhythmias of deep intramural origin. Heart Rhythm 2020;17:1500–1507.

506. Della Bella P, Peretto G, Paglino G, Bisceglia C, Radinovic A, Sala S, et al. Bipolar radiofrequency ablation for ventricular tachycardias originating from the interventricular septum: safety and efficacy in a pilot cohort study. Heart Rhythm 2020;17: 2111–2118.

507. Cuculich PS, Schill MR, Kashani R, Mutic S, Lang A, Cooper D, et al. Noninvasive cardiac radiation for ablation of ventricular tachycardia. N Engl J Med 2017;377: 2325–2336.

508. Robinson CG, Samson PP, Moore KMS, Hugo GD, Knutson N, Mutic S, et al. Phase I/II trial of electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia. Circulation 2019;139:313–321.

509. Anter E, Hutchinson MD, Deo R, Haqqani HM, Callans DJ, Gerstenfeld EP, et al. Surgical ablation of refractory ventricular tachycardia in patients with nonischemic cardiomyopathy. Circ Arrhythm Electrophysiol 2011;4:494–500.

510. Fernández-Armenta J, Berruezo A, Andreu D, Camara O, Silva E, Serra L, et al. Three-dimensional architecture of scar and conducting channels based on high resolution ce-CMR: insights for ventricular tachycardia ablation. Circ Arrhythm Electrophysiol 2013;6:528–537.

511. Mahida S, Sacher F, Dubois R, Sermesant M, Bogun F, Haïssaguerre M, et al. Cardiac imaging in patients with ventricular tachycardia. Circulation 2017;136:2491–2507.

512. Andreu D, Penela D, Acosta J, Fernández-Armenta J, Perea RJ, Soto-Iglesias D, et al. Cardiac magnetic resonance–aided scar dechanneling: influence on acute and longterm outcomes. Heart Rhythm 2017;14:1121–1128.

513. Kuo L, Liang JJ, Nazarian S, Marchlinski FE. Multimodality imaging to guide ventricular tachycardia ablation in patients with non-ischaemic cardiomyopathy. Arrhythm Electrophysiol Rev 2020;8:255–264.

514. Roca-Luque I, Van Breukelen A, Alarcon F, Garre P, Tolosana JM, Borras R, et al. Ventricular scar channel entrances identified by new wideband cardiac magnetic resonance sequence to guide ventricular tachycardia ablation in patients with cardiac defibrillators. Europace 2020;22:598–606.

515. Betensky BP, Marchlinski FE. Outcomes of catheter ablation of ventricular tachycardia in the setting of structural heart disease. Curr Cardiol Rep 2016;18:68.

516. Dukkipati SR, Koruth JS, Choudry S, Miller MA, Whang W, Reddy VY. Catheter ablation of ventricular tachycardia in structural heart disease. J Am Coll Cardiol 2017; 70:2924–2941.

517. Zeppenfeld K. Ventricular tachycardia ablation in nonischemic cardiomyopathy. JACC Clin Electrophysiol 2018;4:1123–1140.

518. Guandalini GS, Liang JJ, Marchlinski FE. Ventricular tachycardia ablation. JACC Clin Electrophysiol 2019;5:1363–1383.

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519. Peichl P, Wichterle D, Pavlu L, Cihak R, Aldhoon B, Kautzner J. Complications of catheter ablation of ventricular tachycardia: a single-center experience. Circ Arrhythm Electrophysiol 2014;7:684–690.

520. Katz DF, Turakhia MP, Sauer WH, Tzou WS, Heath RR, Zipse MM, et al. Safety of ventricular tachycardia ablation in clinical practice: findings from 9699 hospital discharge records. Circ Arrhythm Electrophysiol 2015;8:362–370.

521. Cheung JW, Yeo I, Ip JE, Thomas G, Liu CF, Markowitz SM, et al. Outcomes, costs, and 30-day readmissions after catheter ablation of myocardial infarct–associated ventricular tachycardia in the real world: nationwide readmissions database 2010 to 2015. Circ Arrhythm Electrophysiol 2018;11:e006754.

522. Hendriks AA, Akca F, Dabiri Abkenari L, Khan M, Bhagwandien R, Yap S-C, et al. Safety and clinical outcome of catheter ablation of ventricular arrhythmias using contact force sensing: consecutive case series. J Cardiovasc Electrophysiol 2015;26: 1224–1229.

523. Nogami A. Purkinje-related arrhythmias part I: monomorphic ventricular tachycardias. Pacing Clin Electrophysiol 2011;34:624–650.

524. Lerman BB. Mechanism, diagnosis, and treatment of outflow tract tachycardia. Nat Rev Cardiol 2015;12:597–608.

525. Kobayashi Y. Idiopathic ventricular premature contraction and ventricular tachycardia: distribution of the origin, diagnostic algorithm, and catheter ablation. J Nippon Med Sch 2018;85:87–94.

526. Tada H, Ito S, Naito S, Kurosaki K, Kubota S, Sugiyasu A, et al. Idiopathic ventricular arrhythmia arising from the mitral annulus: a distinct subgroup of idiopathic ventricular arrhythmias. J Am Coll Cardiol 2005;45:877–886.

527. Wasmer K, Köbe J, Dechering DG, Bittner A, Pott C, Mönnig G, et al. Ventricular arrhythmias from the mitral annulus: patient characteristics, electrophysiological findings, ablation, and prognosis. Heart Rhythm 2013;10:783–788.

528. Tada H, Tadokoro K, Ito S, Naito S, Hashimoto T, Kaseno K, et al. Idiopathic ventricular arrhythmias originating from the tricuspid annulus: prevalence, electrocardiographic characteristics, and results of radiofrequency catheter ablation. Heart Rhythm 2007;4:7–16.

529. Yamada T, Doppalapudi H, McElderry HT, Okada T, Murakami Y, Inden Y, et al. Electrocardiographic and electrophysiological characteristics in idiopathic ventricular arrhythmias originating from the papillary muscles in the left ventricle: relevance for catheter ablation. Circ Arrhythm Electrophysiol 2010;3:324–331.

530. Macias C, Nakamura K, Tung R, Boyle NG, Kalyanam S, Bradfield JS. Importance of delayed enhanced cardiac MRI in idiopathic RVOT-VT: differentiating mimics including early stage ARVC and cardiac sarcoidosis. J Atr Fibrillation 2014;7:1097.

531. Heeger C-H, Hayashi K, Kuck K-H, Ouyang F. Catheter ablation of idiopathic ventricular arrhythmias arising from the cardiac outflow tracts—recent insights and techniques for the successful treatment of common and challenging cases. Circ J 2016;80:1073–1086.

532. Pathak RK, Ariyarathna N, Garcia FC, Sanders P, Marchlinski FE. Catheter ablation of idiopathic ventricular arrhythmias. Heart Lung Circ 2019;28:102–109.

533. Yamada T, McElderry HT, Doppalapudi H, Murakami Y, Yoshida Y, Yoshida N, et al. Idiopathic ventricular arrhythmias originating from the aortic root prevalence, electrocardiographic and electrophysiologic characteristics, and results of radiofrequency catheter ablation. J Am Coll Cardiol 2008;52:139–147.

534. Van Herendael H, Garcia F, Lin D, Riley M, Bala R, Cooper J, et al. Idiopathic right ventricular arrhythmias not arising from the outflow tract: prevalence, electrocardiographic characteristics, and outcome of catheter ablation. Heart Rhythm 2011;8: 511–518.

535. Latchamsetty R, Yokokawa M, Morady F, Kim HM, Mathew S, Tilz R, et al. Multicenter outcomes for catheter ablation of idiopathic premature ventricular complexes. JACC Clin Electrophysiol 2015;1:116–123.

536. Liu Y, Fang Z, Yang B, Kojodjojo P, Chen H, Ju W, et al. Catheter ablation of fascicular ventricular tachycardia: long-term clinical outcomes and mechanisms of recurrence. Circ Arrhythm Electrophysiol 2015;8:1443–1451.

537. Hayashi T, Liang JJ, Shirai Y, Kuo L, Muser D, Kubala M, et al. Trends in successful ablation sites and outcomes of ablation for idiopathic outflow tract ventricular arrhythmias. JACC Clin Electrophysiol 2020;6:221–230.

538. Farré J, Wellens HJ. Philippe Coumel: a founding father of modern arrhythmology. Europace 2004;6:464–465.

539. Neira V, Enriquez A, Simpson C, Baranchuk A. Update on long QT syndrome. J Cardiovasc Electrophysiol 2019;30:3068–3078.

540. Winbo A, Paterson DJ. The brain-heart connection in sympathetically triggered inherited arrhythmia syndromes. Heart Lung Circ 2020;29:529–537.

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544. Demirel F, Rasoul S, Elvan A, Ottervanger JP, Dambrink J-HE, Gosselink ATM, et al. Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in patients with ST-elevation myocardial infarction admitted for primary percutaneous coronary intervention: Impact of ventricular fibrillation in STEMI patients. Eur Heart J Acute Cardiovasc Care 2015;4:16–23.

545. Mehta RH, Starr AZ, Lopes RD, Hochman JS, Widimsky P, Pieper KS, et al. Incidence of and outcomes associated with ventricular tachycardia or fibrillation in patients undergoing primary percutaneous coronary intervention. JAMA 2009; 301:1779–1789.

546. Demidova MM, Carlson J, Erlinge D, Platonov PG. Predictors of ventricular fibrillation at reperfusion in patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention. Am J Cardiol 2015;115:417–422.

547. Cheng Y-J, Li Z-Y, Yao F-J, Xu X-J, Ji C-C, Chen X-M, et al. Early repolarization is associated with a significantly increased risk of ventricular arrhythmias and sudden cardiac death in patients with structural heart diseases. Heart Rhythm 2017;14: 1157–1164.

548. Dumas F, Bougouin W, Geri G, Lamhaut L, Rosencher J, Pène F, et al. Emergency percutaneous coronary intervention in post-cardiac arrest patients without ST-segment elevation pattern: insights from the PROCAT II registry. JACC Cardiovasc Interv 2016;9:1011–1018.

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550. Roolvink V, Ibáñez B, Ottervanger JP, Pizarro G, van Royen N, Mateos A, et al. Early intravenous beta-blockers in patients with ST-segment elevation myocardial infarction before primary percutaneous coronary intervention. J Am Coll Cardiol 2016;67: 2705–2715.

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555. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med 2002;346:884–890.

556. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991;324:781–788.

557. Baudry G, Sonneville R, Waintraub X, Lebreton G, Deguillard C, Mertens E, et al. Extracorporeal membrane oxygenation to support life-threatening drug-refractory electrical storm. Crit Care Med 2020;48:e856–e863.

558. Demidova MM, Smith JG, Höijer C-J, Holmqvist F, Erlinge D, Platonov PG. Prognostic impact of early ventricular fibrillation in patients with ST-elevation myocardial infarction treated with primary PCI. Eur Heart J Acute Cardiovasc Care 2012; 1:302–311.

559. Podolecki T, Lenarczyk R, Kowalczyk J, Jedrzejczyk-Patej E, Chodor P, Mazurek M, et al. Prognostic significance of complex ventricular arrhythmias complicating ST-segment elevation myocardial infarction. Am J Cardiol 2018;121:805–809.

560. Bougouin W, Marijon E, Puymirat E, Defaye P, Celermajer DS, Le Heuzey J-Y, et al. Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry. Eur Heart J 2014;35:116–122.

561. Liang JJ, Hodge DO, Mehta RA, Russo AM, Prasad A, Cha Y-M. Outcomes in patients with sustained ventricular tachyarrhythmias occurring within 48 h of acute myocardial infarction: when is ICD appropriate? Europace 2014;16:1759–1766.

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563. Sueda S, Kohno H. Optimal medications and appropriate implantable cardioverterdefibrillator shocks in aborted sudden cardiac death due to coronary spasm. Intern Med 2018;57:1361–1369.

564. Rodríguez-Mañero M, Oloriz T, le Polain de Waroux J-B, Burri H, Kreidieh B, de Asmundis C, et al. Long-term prognosis of patients with life-threatening ventricular arrhythmias induced by coronary artery spasm. Europace 2018;20:851–858.

565. Solomon SD, Zelenkofske S, McMurray JJV, Finn PV, Velazquez E, Ertl G, et al. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005;352:2581–2588.

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566. Busk M, Maeng M, Kristensen SD, Thuesen L, Krusell LR, Mortensen LS, et al. Timing, causes, and predictors of death after three years’ follow-up in the Danish Multicenter Randomized Study of Fibrinolysis versus Primary Angioplasty in Acute Myocardial Infarction (DANAMI-2) trial. Am J Cardiol 2009;104:210–215.

567. St John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moyé LA, Dagenais GR, et al. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation 1994;89:68–75.

568. Søholm H, Lønborg J, Andersen MJ, Vejlstrup N, Engstrøm T, Møller JE, et al. Repeated echocardiography after first ever ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention–is it necessary? Eur Heart J Acute Cardiovasc Care 2015;4:528–536.

569. Steinbeck G, Andresen D, Seidl K, Brachmann J, Hoffmann E, Wojciechowski D, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009;361:1427–1436.

570. Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481–2488.

571. Exner DV, Kavanagh KM, Slawnych MP, Mitchell LB, Ramadan D, Aggarwal SG, et al. Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 2007;50:2275–2284.

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573. Daubert MA, White JA, Al-Khalidi HR, Velazquez EJ, Rao SV, Crowley AL, et al. Cardiac remodeling after large ST-elevation myocardial infarction in the current therapeutic era. Am Heart J 2020;223:87–97.

574. Chew DS, Heikki H, Schmidt G, Kavanagh KM, Dommasch M, Bloch Thomsen PE, et al. Change in left ventricular ejection fraction following first myocardial infarction and outcome. JACC Clin Electrophysiol 2018;4:672–682.

575. Bänsch D, Oyang F, Antz M, Arentz T, Weber R, Val-Mejias JE, et al. Successful catheter ablation of electrical storm after myocardial infarction. Circulation 2003;108: 3011–3016.

576. Altmann DR, Mutschelknauss M, Ehl N, Koller M, Schaer B, Jörg L, et al. Prevalence of severely impaired left ventricular ejection fraction after reperfused ST-elevation myocardial infarction. Swiss Med Wkly 2013;143:w13869.

577. Shen L, Jhund PS, Petrie MC, Claggett BL, Barlera S, Cleland JGF, et al. Declining risk of sudden death in heart failure. N Engl J Med 2017;377:41–51.

578. Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997;349:675–682.

579. Julian DG, Camm AJ, Frangin G, Janse MJ, Munoz A, Schwartz PJ, et al. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 1997;349:667–674.

580. Clemens M, Peichl P, Wichterle D, Pavlů L, Čihák R, Aldhoon B, et al. Catheter ablation of ventricular tachycardia as the first-line therapy in patients with coronary artery disease and preserved left ventricular systolic function: long-term results: VT ablation in patients with preserved LV function. J Cardiovasc Electrophysiol 2015;26:1105–1110.

581. Pacifico A, Hohnloser SH, Williams JH, Tao B, Saksena S, Henry PD, et al. Prevention of implantable-defibrillator shocks by treatment with sotalol. D, L-Sotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 1999; 340:1855–1862.

582. Willems S, Tilz RR, Steven D, Kääb S, Wegscheider K, Gellér L, et al. Preventive or deferred ablation of ventricular tachycardia in patients with ischemic cardiomyopathy and implantable defibrillator (BERLIN VT): a multicenter randomized trial. Circulation 2020;141:1057–1067.

583. Kuck K-H, Tilz RR, Deneke T, Hoffmann BA, Ventura R, Hansen PS, et al. Impact of substrate modification by catheter ablation on implantable cardioverter–defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (substrate modification study). Circ Arrhythm Electrophysiol 2017;10:e004422.

584. Olshansky B, Hahn EA, Hartz VL, Prater SP, Mason JW. Clinical significance of syncope in the electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial. The ESVEM Investigators. Am Heart J 1999;137:878–886.

585. Molossi S, Agrawal H, Mery CM, Krishnamurthy R, Masand P, Sexson Tejtel SK, et al. Outcomes in anomalous aortic origin of a coronary artery following a prospective standardized approach. Circ Cardiovasc Interv 2020;13:e008445.

586. Krasuski RA, Magyar D, Hart S, Kalahasti V, Lorber R, Hobbs R, et al. Long-term outcome and impact of surgery on adults with coronary arteries originating from the opposite coronary cusp. Circulation 2011;123:154–162.

587. Jegatheeswaran A, Devlin PJ, McCrindle BW, Williams WG, Jacobs ML, Blackstone EH, et al. Features associated with myocardial ischemia in anomalous aortic origin of a coronary artery: a congenital heart surgeons’ society study. J Thorac Cardiovasc Surg 2019;158:822–834.

588. Jegatheeswaran A, Devlin PJ, Williams WG, Brothers JA, Jacobs ML, DeCampli WM, et al. Outcomes after anomalous aortic origin of a coronary artery repair: a congenital heart surgeons’ society study. J Thorac Cardiovasc Surg 2020;160: 757–771.

589. Hoffmayer KS, Bhave PD, Marcus GM, James CA, Tichnell C, Chopra N, et al. An electrocardiographic scoring system for distinguishing right ventricular outflow tract arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia. Heart Rhythm 2013;10:477–482.

590. Yokokawa M, Siontis KC, Kim HM, Stojanovska J, Latchamsetty R, Crawford T, et al. Value of cardiac magnetic resonance imaging and programmed ventricular stimulation in patients with frequent premature ventricular complexes undergoing radiofrequency ablation. Heart Rhythm 2017;14:1695–1701.

591. Muser D, Santangeli P, Castro SA, Casado Arroyo R, Maeda S, Benhayon DA, et al. Risk stratification of patients with apparently idiopathic premature ventricular contractions: a multicenter international CMR registry. JACC Clin Electrophysiol 2020;6: 722–735.

592. Kjekshus J, Bathen J, Orning OM, Storstein L. A double-blind, crossover comparison of flecainide acetate and disopyramide phosphate in the treatment of ventricular premature complexes. Am J Cardiol 1984;53:72B–78B.

593. Hamon D, Swid MA, Rajendran PS, Liu A, Boyle NG, Shivkumar K, et al. Premature ventricular contraction diurnal profiles predict distinct clinical characteristics and beta-blocker responses. J Cardiovasc Electrophysiol 2019;30:836–843.

594. Primeau R, Agha A, Giorgi C, Shenasa M, Nadeau R. Long term efficacy and toxicity of amiodarone in the treatment of refractory cardiac arrhythmias. Can J Cardiol 1989;5:98–104.

595. Ling Z, Liu Z, Su L, Zipunnikov V, Wu J, Du H, et al. Radiofrequency ablation versus antiarrhythmic medication for treatment of ventricular premature beats from the right ventricular outflow tract: prospective randomized study. Circ Arrhythm Electrophysiol 2014;7:237–243.

596. Baksiene D, Sileikiene R, Sileikis V, Kazakevicius T, Zabiela V, Zebiene M, et al. Idiopathic ventricular tachycardia in children: curative therapy with radiofrequency ablation. Medicina (Kaunas) 2007;43:803–807.

597. Blaufox AD, Felix GL, Saul JP, Pediatric Catheter Ablation Registry. Radiofrequency catheter ablation in infants,/=18 months old: when is it done and how do they fare?: Short-term data from the pediatric ablation registry. Circulation 2001;104: 2803–2808.

598. Lapage MJ, Bradley DJ, Dick M. Verapamil in infants: an exaggerated fear? Pediatr Cardiol 2013;34:1532–1534.

599. Lee AKY, Andrade J, Hawkins NM, Alexander G, Bennett MT, Chakrabarti S, et al. Outcomes of untreated frequent premature ventricular complexes with normal left ventricular function. Heart 2019;105:1408–1413.

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601. van Huls van Taxis CFB, Piers SRD, de Riva Silva M, Dekkers OM, Pijnappels DA, Schalij MJ, et al. Fatigue as presenting symptom and a high burden of premature ventricular contractions are independently associated with increased ventricular wall stress in patients with normal left ventricular function. Circ Arrhythm Electrophysiol 2015;8:1452–1459.

602. Sharma N, Cortez D, Imundo JR. High burden of premature ventricular contractions in structurally normal hearts: to worry or not in pediatric patients? Ann Noninvasive Electrocardiol 2019;24:e12663.

603. Niwano S, Wakisaka Y, Niwano H, Fukaya H, Kurokawa S, Kiryu M, et al. Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function. Heart 2009;95:1230–1237.

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605. Komatsu Y, Nogami A, Kurosaki K, Morishima I, Masuda K, Ozawa T, et al. Fascicular ventricular tachycardia originating from papillary muscles: Purkinje network involvement in the reentrant circuit. Circ Arrhythm Electrophysiol 2017;10: e004549.

606. Kirk CR, Gibbs JL, Thomas R, Radley-Smith R, Qureshi SA. Cardiovascular collapse after verapamil in supraventricular tachycardia. Arch Dis Child 1987;62:1265–1266.

607. Duffee DF, Shen WK, Smith HC. Suppression of frequent premature ventricular contractions and improvement of left ventricular function in patients with presumed idiopathic dilated cardiomyopathy. Mayo Clin Proc 1998;73:430–433.

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608. Chugh SS, Shen WK, Luria DM, Smith HC. First evidence of premature ventricular complex-induced cardiomyopathy: a potentially reversible cause of heart failure. J Cardiovasc Electrophysiol 2000;11:328–329.

609. Penela D, Van Huls Van Taxis C, Van Huls Vans Taxis C, Aguinaga L, Fernández-Armenta J, Mont L, et al. Neurohormonal, structural, and functional recovery pattern after premature ventricular complex ablation is independent of structural heart disease status in patients with depressed left ventricular ejection fraction: a prospective multicenter study. J Am Coll Cardiol 2013;62:1195–1202.

610. Penela D, Acosta J, Aguinaga L, Tercedor L, Ordoñez A, Fernández-Armenta J, et al. Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: safety of withholding the implant. Heart Rhythm 2015;12:2434–2442.

611. Voskoboinik A, Hadjis A, Alhede C, Im SI, Park H, Moss J, et al. Predictors of adverse outcome in patients with frequent premature ventricular complexes: the ABC-VT risk score. Heart Rhythm 2020;17:1066–1074.

612. Lee A, Denman R, Haqqani HM. Ventricular ectopy in the context of left ventricular systolic dysfunction: risk factors and outcomes following catheter ablation. Heart Lung Circ 2019;28:379–388.

613. Sadron Blaye-Felice M, Hamon D, Sacher F, Pascale P, Rollin A, Duparc A, et al. Premature ventricular contraction-induced cardiomyopathy: related clinical and electrophysiologic parameters. Heart Rhythm 2016;13:103–110.

614. Penela D, Fernández-Armenta J, Aguinaga L, Tercedor L, Ordoñez A, Bisbal F, et al. Clinical recognition of pure premature ventricular complex-induced cardiomyopathy at presentation. Heart Rhythm 2017;14:1864–1870.

615. Aquaro GD, Pingitore A, Strata E, Di Bella G, Molinaro S, Lombardi M. Cardiac magnetic resonance predicts outcome in patients with premature ventricular complexes of left bundle branch block morphology. J Am Coll Cardiol 2010;56: 1235–1243.

616. Oebel S, Dinov B, Arya A, Hilbert S, Sommer P, Bollmann A, et al. ECG morphology of premature ventricular contractions predicts the presence of myocardial fibrotic substrate on cardiac magnetic resonance imaging in patients undergoing ablation. J Cardiovasc Electrophysiol 2017;28:1316–1323.

617. Mountantonakis SE, Frankel DS, Gerstenfeld EP, Dixit S, Lin D, Hutchinson MD, et al. Reversal of outflow tract ventricular premature depolarization–induced cardiomyopathy with ablation: effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome. Heart Rhythm 2011;8:1608–1614.

618. Zang M, Zhang T, Mao J, Zhou S, He B. Beneficial effects of catheter ablation of frequent premature ventricular complexes on left ventricular function. Heart 2014; 100:787–793.

619. Wijnmaalen AP, Delgado V, Schalij MJ, van Huls van Taxis CFB, Holman ER, Bax JJ, et al. Beneficial effects of catheter ablation on left ventricular and right ventricular function in patients with frequent premature ventricular contractions and preserved ejection fraction. Heart 2010;96:1275–1280.

620. Bogun F, Crawford T, Reich S, Koelling TM, Armstrong W, Good E, et al. Radiofrequency ablation of frequent, idiopathic premature ventricular complexes: comparison with a control group without intervention. Heart Rhythm 2007;4: 863–867.

621. Sarrazin J-F, Labounty T, Kuhne M, Crawford T, Armstrong WF, Desjardins B, et al. Impact of radiofrequency ablation of frequent post-infarction premature ventricular complexes on left ventricular ejection fraction. Heart Rhythm 2009;6: 1543–1549.

622. El Kadri M, Yokokawa M, Labounty T, Mueller G, Crawford T, Good E, et al. Effect of ablation of frequent premature ventricular complexes on left ventricular function in patients with nonischemic cardiomyopathy. Heart Rhythm 2015;12: 706–713.

623. Lakkireddy D, Di Biase L, Ryschon K, Biria M, Swarup V, Reddy YM, et al. Radiofrequency ablation of premature ventricular ectopy improves the efficacy of cardiac resynchronization therapy in nonresponders. J Am Coll Cardiol 2012; 60:1531–1539.

624. Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival trial of antiarrhythmic therapy in congestive heart failure. N Engl J Med 1995;333:77–82.

625. Zhong L, Lee Y-H, Huang X-M, Asirvatham SJ, Shen W-K, Friedman PA, et al. Relative efficacy of catheter ablation vs antiarrhythmic drugs in treating premature ventricular contractions: a single-center retrospective study. Heart Rhythm 2014; 11:187–193.

626. Hyman MC, Mustin D, Supple G, Schaller RD, Santangeli P, Arkles J, et al. Class IC antiarrhythmic drugs for suspected premature ventricular contraction-induced cardiomyopathy. Heart Rhythm 2018;15:159–163.

627. Laurent G, Saal S, Amarouch MY, Béziau DM, Marsman RFJ, Faivre L, et al. Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy. J Am Coll Cardiol 2012;60:144–156.

628. Calloe K, Broendberg AK, Christensen AH, Pedersen LN, Olesen MS, de Los Angeles Tejada M, et al. Multifocal atrial and ventricular premature contractions

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629. Mann SA, Castro ML, Ohanian M, Guo G, Zodgekar P, Sheu A, et al. R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy. J Am Coll Cardiol 2012;60:1566–1573.

630. Beckermann TM, McLeod K, Murday V, Potet F, George AL. Novel SCN5A mutation in amiodarone-responsive multifocal ventricular ectopy-associated cardiomyopathy. Heart Rhythm 2014;11:1446–1453.

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632. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008;29:270–276.

633. Codd MB, Sugrue DD, Gersh BJ, Melton LJ. Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975–1984. Circulation 1989;80:564–572.

634. Weintraub RG, Semsarian C, Macdonald P. Dilated cardiomyopathy. Lancet 2017; 390:400–414.

635. Beggs SAS, Jhund PS, Jackson CE, McMurray JJV, Gardner RS. Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis. Heart 2018;104:144–150.

636. Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 2006;296: 1867–1876.

637. Pahl E, Sleeper LA, Canter CE, Hsu DT, Lu M, Webber SA, et al. Incidence of and risk factors for sudden cardiac death in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry. J Am Coll Cardiol 2012;59: 607–615.

638. Bharucha T, Lee KJ, Daubeney PEF, Nugent AW, Turner C, Sholler GF, et al. Sudden death in childhood cardiomyopathy: results from a long-term national population-based study. J Am Coll Cardiol 2015;65:2302–2310.

639. Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J 2016;37: 1850–1858.

640. Asselbergs FW, Sammani A, Elliott P, Gimeno JR, Tavazzi L, Tendera M, et al. Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry. ESC Heart Fail 2021;8:95–105.

641. Ader F, De Groote P, Réant P, Rooryck-Thambo C, Dupin-Deguine D, Rambaud C, et al. FLNC pathogenic variants in patients with cardiomyopathies: prevalence and genotype-phenotype correlations. Clin Genet 2019;96:317–329.

642. Kayvanpour E, Sedaghat-Hamedani F, Amr A, Lai A, Haas J, Holzer DB, et al. Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals. Clin Res Cardiol 2017;106:127–139.

643. Ortiz-Genga MF, Cuenca S, Dal Ferro M, Zorio E, Salgado-Aranda R, Climent V, et al. Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies. J Am Coll Cardiol 2016;68:2440–2451.

644. van den Hoogenhof MMG, Beqqali A, Amin AS, van der Made I, Aufiero S, Khan MAF, et al. RBM20 mutations induce an arrhythmogenic dilated cardiomyopathy related to disturbed calcium handling. Circulation 2018;138:1330–1342.

645. Gigli M, Merlo M, Graw SL, Barbati G, Rowland TJ, Slavov DB, et al. Genetic risk of arrhythmic phenotypes in patients with dilated cardiomyopathy. J Am Coll Cardiol 2019;74:1480–1490.

646. Heliö T, Elliott P, Koskenvuo JW, Gimeno JR, Tavazzi L, Tendera M, et al. ESC EORP cardiomyopathy registry: real-life practice of genetic counselling and testing in adult cardiomyopathy patients. ESC Heart Fail 2020;7:3013–3021.

647. Elming MB, Nielsen JC, Haarbo J, Videbæk L, Korup E, Signorovitch J, et al. Age and outcomes of primary prevention implantable cardioverter-defibrillators in patients with nonischemic systolic heart failure. Circulation 2017;136:1772–1780.

648. Kristensen SL, Levy WC, Shadman R, Nielsen JC, Haarbo J, Videbæk L, et al. Risk models for prediction of implantable cardioverter-defibrillator benefit. JACC Heart Fail 2019;7:717–724.

649. Wolff G, Lin Y, Karathanos A, Brockmeyer M, Wolters S, Nowak B, et al. Implantable cardioverter/defibrillators for primary prevention in dilated cardiomyopathy post-DANISH: an updated meta-analysis and systematic review of randomized controlled trials. Clin Res Cardiol 2017;106:501–513.

650. Kadish A, Dyer A, Daubert JP, Quigg R, Estes NAM, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151–2158.

651. Klem I, Klein M, Khan M, Yang EY, Nabi F, Ivanov A, et al. Relationship of LVEF and myocardial scar to long-term mortality risk and mode of death in patients with nonischemic cardiomyopathy. Circulation 2021;143:1343–1358.

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652. van Rijsingen IAW, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, van der Kooi AJ, et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study. J Am Coll Cardiol 2012;59:493–500.

653. Thuillot M, Maupain C, Gandjbakhch E, Waintraub X, Hidden-Lucet F, Isnard R, et al. External validation of risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers. Eur J Heart Fail 2019;21:253–254.

654. Pasotti M, Klersy C, Pilotto A, Marziliano N, Rapezzi C, Serio A, et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol 2008;52:1250–1260.

655. Skjølsvik ET, Hasselberg NE, Dejgaard LA, Lie ØH, Andersen K, Holm T, et al. Exercise is associated with impaired left ventricular systolic function in patients with lamin A/C genotype. J Am Heart Assoc 2020;9:e012937.

656. Verstraelen TE, van Lint FHM, Bosman LP, de Brouwer R, Proost VM, Abeln BGS, et al. Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction. Eur Heart J 2021;42: 2842–2850.

657. Knight BP, Goyal R, Pelosi F, Flemming M, Horwood L, Morady F, et al. Outcome of patients with nonischemic dilated cardiomyopathy and unexplained syncope treated with an implantable defibrillator. J Am Coll Cardiol 1999;33:1964–1970.

658. Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. JAMA 2004;292:2874–2879.

659. Merlo M, Gentile P, Artico J, Cannatà A, Paldino A, De Angelis G, et al. Arrhythmic risk stratification in patients with dilated cardiomyopathy and intermediate left ventricular dysfunction. J Cardiovasc Med (Hagerstown) 2019;20:343–350.

660. Zecchin M, Di Lenarda A, Gregori D, Merlo M, Pivetta A, Vitrella G, et al. Are nonsustained ventricular tachycardias predictive of major arrhythmias in patients with dilated cardiomyopathy on optimal medical treatment? Pacing Clin Electro 2008;31: 290–299.

661. Link MS, Costeas XF, Griffith JL, Colburn CD, Estes NA, Wang PJ. High incidence of appropriate implantable cardioverter-defibrillator therapy in patients with syncope of unknown etiology and inducible ventricular arrhythmias. J Am Coll Cardiol 1997; 29:370–375.

662. Di Marco A, Brown PF, Bradley J, Nucifora G, Claver E, de Frutos F, et al. Improved risk stratification for ventricular arrhythmias and sudden death in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2021;77:2890–2905.

663. Kumar S, Romero J, Mehta NK, Fujii A, Kapur S, Baldinger SH, et al. Long-term outcomes after catheter ablation of ventricular tachycardia in patients with and without structural heart disease. Heart Rhythm 2016;13:1957–1963.

664. Muser D, Santangeli P, Castro SA, Pathak RK, Liang JJ, Hayashi T, et al. Long-term outcome after catheter ablation of ventricular tachycardia in patients with nonischemic dilated cardiomyopathy. Circ Arrhythm Electrophysiol 2016;9:e004328.

665. Kumar S, Androulakis AFA, Sellal J-M, Maury P, Gandjbakhch E, Waintraub X, et al. Multicenter experience with catheter ablation for ventricular tachycardia in lamin A/C cardiomyopathy. Circ Arrhythm Electrophysiol 2016;9:e004357.

666. Oloriz T, Silberbauer J, Maccabelli G, Mizuno H, Baratto F, Kirubakaran S, et al. Catheter ablation of ventricular arrhythmia in nonischemic cardiomyopathy: anteroseptal versus inferolateral scar sub-types. Circ Arrhythm Electrophysiol 2014;7: 414–423.

667. Francone M. Role of cardiac magnetic resonance in the evaluation of dilated cardiomyopathy: diagnostic contribution and prognostic significance. ISRN Radiol 2014; 2014:365404.

668. Goldberger JJ, Subačius H, Patel T, Cunnane R, Kadish AH. Sudden cardiac death risk stratification in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2014;63:1879–1889.

669. Ebert M, Wijnmaalen AP, de Riva M, Trines SA, Androulakis AFA, Glashan CA, et al. Prevalence and prognostic impact of pathogenic variants in patients with dilated cardiomyopathy referred for ventricular tachycardia ablation. JACC Clin Electrophysiol 2020;6:1103–1114.

670. Corrado D, Link MS, Calkins H. Arrhythmogenic right ventricular cardiomyopathy. N Engl J Med 2017;376:1489–1490.

671. Quarta G, Muir A, Pantazis A, Syrris P, Gehmlich K, Garcia-Pavia P, et al. Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria. Circulation 2011;123:2701–2709.

672. Bhonsale A, Groeneweg JA, James CA, Dooijes D, Tichnell C, Jongbloed JDH, et al. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/ cardiomyopathy-associated mutation carriers. Eur Heart J 2015;36:847–855.

673. Rigato I, Bauce B, Rampazzo A, Zorzi A, Pilichou K, Mazzotti E, et al. Compound and digenic heterozygosity predicts lifetime arrhythmic outcome and sudden cardiac death in desmosomal gene-related arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet 2013;6:533–542.

674. te Riele ASJM, James CA, Groeneweg JA, Sawant AC, Kammers K, Murray B, et al. Approach to family screening in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Eur Heart J 2016;37:755–763.

675. Chivulescu M, Lie ØH, Popescu BA, Skulstad H, Edvardsen T, Jurcut RO, et al. High penetrance and similar disease progression in probands and in family members with arrhythmogenic cardiomyopathy. Eur Heart J 2020;41:1401–1410.

676. Rastegar N, Te Riele ASJM, James CA, Bhonsale A, Murray B, Tichnell C, et al. Fibrofatty changes: incidence at cardiac MR imaging in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Radiology 2016;280:405–412.

677. Aquaro GD, Barison A, Todiere G, Grigoratos C, Ait Ali L, Di Bella G, et al. Usefulness of combined functional assessment by cardiac magnetic resonance and tissue characterization versus task force criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 2016;118:1730–1736.

678. te Riele ASJM, Bhonsale A, James CA, Rastegar N, Murray B, Burt JR, et al. Incremental value of cardiac magnetic resonance imaging in arrhythmic risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol 2013;62:1761–1769.

679. Corrado D, van Tintelen PJ, McKenna WJ, Hauer RNW, Anastastakis A, Asimaki A, et al. Arrhythmogenic right ventricular cardiomyopathy: evaluation of the current diagnostic criteria and differential diagnosis. Eur Heart J 2020;41:1414–1429.

680. Sen-Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna WJ. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation 2007;115:1710–1720.

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683. Saberniak J, Hasselberg NE, Borgquist R, Platonov PG, Sarvari SI, Smith H, et al. Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members. Eur J Heart Fail 2014;16:1337–1344.

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686. Ruwald A-C, Marcus F, Estes NAM, Link M, McNitt S, Polonsky B, et al. Association of competitive and recreational sport participation with cardiac events in patients with arrhythmogenic right ventricular cardiomyopathy: results from the North American multidisciplinary study of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2015;36:1735–1743.

687. Sawant AC, te Riele ASJM, Tichnell C, Murray B, Bhonsale A, Tandri H, et al. Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers. Heart Rhythm 2016;13:199–207.

688. Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right ventricular cardiomyopathy and sudden death in young people. N Engl J Med 1988;318:129–133.

689. Finocchiaro G, Papadakis M, Robertus J-L, Dhutia H, Steriotis AK, Tome M, et al. Etiology of sudden death in sports: insights from a United Kingdom Regional Registry. J Am Coll Cardiol 2016;67:2108–2115.

690. Marcus GM, Glidden DV, Polonsky B, Zareba W, Smith LM, Cannom DS, et al. Efficacy of antiarrhythmic drugs in arrhythmogenic right ventricular cardiomyopathy: a report from the North American ARVC Registry. J Am Coll Cardiol 2009; 54:609–615.

691. Hulot J-S, Jouven X, Empana J-P, Frank R, Fontaine G. Natural history and risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation 2004;110:1879–1884.

692. Wang W, Cadrin-Tourigny J, Bhonsale A, Tichnell C, Murray B, Monfredi O, et al. Arrhythmic outcome of arrhythmogenic right ventricular cardiomyopathy patients without implantable defibrillators. J Cardiovasc Electrophysiol 2018;29:1396–1402.

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694. Brun F, Groeneweg JA, Gear K, Sinagra G, van der Heijden J, Mestroni L, et al. Risk stratification in arrhythmic right ventricular cardiomyopathy without implantable cardioverter-defibrillators. JACC Clin Electrophysiol 2016;2:558–564.

695. Bhonsale A, James CA, Tichnell C, Murray B, Gagarin D, Philips B, et al. Incidence and predictors of implantable cardioverter-defibrillator therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing implantable cardioverter-defibrillator implantation for primary prevention. J Am Coll Cardiol 2011;58:1485–1496.

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697. Platonov PG, Haugaa KH, Bundgaard H, Svensson A, Gilljam T, Hansen J, et al. Primary prevention of sudden cardiac death with implantable cardioverterdefibrillator therapy in patients with arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 2019;123:1156–1162.

698. Link MS, Laidlaw D, Polonsky B, Zareba W, McNitt S, Gear K, et al. Ventricular arrhythmias in the North American multidisciplinary study of ARVC: predictors, characteristics, and treatment. J Am Coll Cardiol 2014;64:119–125.

699. Schinkel AFL. Implantable cardioverter defibrillators in arrhythmogenic right ventricular dysplasia/cardiomyopathy: patient outcomes, incidence of appropriate and inappropriate interventions, and complications. Circ Arrhythm Electrophysiol 2013;6:562–568.

700. Corrado D, Leoni L, Link MS, Della Bella P, Gaita F, Curnis A, et al. Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation 2003; 108:3084–3091.

701. Mazzanti A, Ng K, Faragli A, Maragna R, Chiodaroli E, Orphanou N, et al. Arrhythmogenic right ventricular cardiomyopathy: clinical course and predictors of arrhythmic risk. J Am Coll Cardiol 2016;68:2540–2550.

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704. Saguner AM, Vecchiati A, Baldinger SH, Rüeger S, Medeiros-Domingo A, Mueller-Burri AS, et al. Different prognostic value of functional right ventricular parameters in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circ Cardiovasc Imaging 2014;7:230–239.

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706. Orgeron GM, Te Riele A, Tichnell C, Wang W, Murray B, Bhonsale A, et al. Performance of the 2015 international task force consensus statement risk stratification algorithm for implantable cardioverter-defibrillator placement in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Arrhythm Electrophysiol 2018;11:e005593.

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710. Ermakov S, Gerstenfeld EP, Svetlichnaya Y, Scheinman MM. Use of flecainide in combination antiarrhythmic therapy in patients with arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm 2017;14:564–569.

711. Canpolat U, Kabakçi G, Aytemir K, Dural M, Şahiner L, Yorgun H, et al. Fragmented QRS complex predicts the arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia: frQRS and outcomes in ARVC/D. J Cardiovasc Electrophysiol 2013;24:1260–1266.

712. Martin A, Crawford J, Skinner JR, Smith W. High arrhythmic burden but low mortality during long-term follow-up in arrhythmogenic right ventricular cardiomyopathy. Heart Lung Circ 2016;25:275–281.

713. Santangeli P, Dello Russo A, Pieroni M, Casella M, Di Biase L, Burkhardt JD, et al. Fragmented and delayed electrograms within fibrofatty scar predict arrhythmic events in arrhythmogenic right ventricular cardiomyopathy: Results from a prospective risk stratification study. Heart Rhythm 2012;9:1200–1206.

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715. Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology/ American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2020;142:e533–e557.

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727. Maron BJ, Rowin EJ, Casey SA, Link MS, Lesser JR, Chan RHM, et al. Hypertrophic cardiomyopathy in adulthood associated with low cardiovascular mortality with contemporary management strategies. J Am Coll Cardiol 2015;65:1915–1928.

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730. Lorenzini M, Anastasiou Z, O’Mahony C, Guttman OP, Gimeno JR, Monserrat L, et al. Mortality among referral patients with hypertrophic cardiomyopathy vs the general European population. JAMA Cardiol 2020;5:73–80.

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737. Rowin EJ, Maron BJ, Haas TS, Garberich RF, Wang W, Link MS, et al. Hypertrophic cardiomyopathy with left ventricular apical aneurysm: implications for risk stratification and management. J Am Coll Cardiol 2017;69:761–773.

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750. Dallaglio PD, di Marco A, Moreno Weidmann Z, Perez L, Alzueta J, García-Alberola A, et al. Antitachycardia pacing for shock prevention in patients with hypertrophic cardiomyopathy and ventricular tachycardia. Heart Rhythm 2020;17:1084–1091.

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753. Igarashi M, Nogami A, Kurosaki K, Hanaki Y, Komatsu Y, Fukamizu S, et al. Radiofrequency catheter ablation of ventricular tachycardia in patients with hypertrophic cardiomyopathy and apical aneurysm. JACC Clin Electrophysiol 2018;4: 339–350.

754. Dukkipati SR, d’Avila A, Soejima K, Bala R, Inada K, Singh S, et al. Long-term outcomes of combined epicardial and endocardial ablation of monomorphic ventricular tachycardia related to hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol 2011;4:185–194.

755. Ross SB, Singer ES, Driscoll E, Nowak N, Yeates L, Puranik R, et al. Genetic architecture of left ventricular noncompaction in adults. Hum Genome Var 2020;7:33.

756. Weir-McCall JR, Yeap PM, Papagiorcopulo C, Fitzgerald K, Gandy SJ, Lambert M, et al. Left ventricular noncompaction: anatomical phenotype or distinct cardiomyopathy? J Am Coll Cardiol 2016;68:2157–2165.

757. Aung N, Doimo S, Ricci F, Sanghvi MM, Pedrosa C, Woodbridge SP, et al. Prognostic significance of left ventricular noncompaction: systematic review and meta-analysis of observational studies. Circ Cardiovasc Imaging 2020;13:e009712.

758. Grigoratos C, Barison A, Ivanov A, Andreini D, Amzulescu M-S, Mazurkiewicz L, et al. Meta-analysis of the prognostic role of late gadolinium enhancement and global systolic impairment in left ventricular noncompaction. JACC Cardiovasc Imaging 2019;12:2141–2151.

759. Richard P, Ader F, Roux M, Donal E, Eicher J-C, Aoutil N, et al. Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity. Clin Genet 2019;95:356–367.

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762. Sperry BW, Ikram A, Hachamovitch R, Valent J, Vranian MN, Phelan D, et al. Efficacy of chemotherapy for light-chain amyloidosis in patients presenting with symptomatic heart failure. J Am Coll Cardiol 2016;67:2941–2948.

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765. Punnoose AR, Kaltman JR, Pastor W, McCarter R, He J, Spurney CF. Cardiac disease burden and risk of mortality in hospitalized muscular dystrophy patients. Pediatr Cardiol 2016;37:1290–1296.

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770. Menon SC, Etheridge SP, Liesemer KN, Williams RV, Bardsley T, Heywood MC, et al. Predictive value of myocardial delayed enhancement in Duchenne muscular dystrophy. Pediatr Cardiol 2014;35:1279–1285.

771. Florian A, Ludwig A, Engelen M, Waltenberger J, Rösch S, Sechtem U, et al. Left ventricular systolic function and the pattern of late-gadolinium-enhancement independently and additively predict adverse cardiac events in muscular dystrophy patients. J Cardiovasc Magn Reson 2014;16:81.

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773. Trachtenberg BH, Hare JM. Inflammatory cardiomyopathic syndromes. Circ Res 2017;121:803–818.

774. Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, et al. Macrophages facilitate electrical conduction in the heart. Cell 2017;169:510–522.

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776. Adamo L, Rocha-Resende C, Prabhu SD, Mann DL. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol 2020;17:269–285.

777. Sagar S, Liu PP, Cooper LT. Myocarditis. Lancet 2012;379:738–747.

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780. Lynge TH, Nielsen TS, Gregers Winkel B, Tfelt-Hansen J, Banner J. Sudden cardiac death caused by myocarditis in persons aged 1–49 years: a nationwide study of 14 294 deaths in Denmark. Forensic Sci Res 2019;4:247–256.

781. Maron BJ, Udelson JE, Bonow RO, Nishimura RA, Ackerman MJ, Estes NAM, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis. J Am Coll Cardiol 2015;66:2362–2371.

782. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, et al. Update on myocarditis. J Am Coll Cardiol 2012;59:779–792.

783. Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34: 2636–2648.

784. Singh V, Mendirichaga R, Savani GT, Rodriguez A, Blumer V, Elmariah S, et al. Comparison of utilization trends, indications, and complications of endomyocardial biopsy in native versus donor hearts (from the Nationwide Inpatient Sample 2002 to 2014). Am J Cardiol 2018;121:356–363.

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787. Anderson BR, Silver ES, Richmond ME, Liberman L. Usefulness of arrhythmias as predictors of death and resource utilization in children with myocarditis. Am J Cardiol 2014;114:1400–1405.

788. Kandolin R, Lehtonen J, Salmenkivi K, Räisänen-Sokolowski A, Lommi J, Kupari M. Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression. Circ Heart Fail 2013;6:15–22.

789. Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis—natural history and treatment. N Engl J Med 1997;336:1860–1866.

790. McMurray JJV, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33: 1787–1847.

791. Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis 2010;52:274–288.

792. JCS Joint Working Group. Guidelines for diagnosis and treatment of myocarditis (JCS 2009): digest version. Circ J 2011;75:734–743.

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794. Rosier L, Zouaghi A, Barré V, Martins R, Probst V, Marijon E, et al. High risk of sustained ventricular arrhythmia recurrence after acute myocarditis. J Clin Med 2020;9: E848.

795. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807–1816.

796. D’Ambrosio A, Patti G, Manzoli A, Sinagra G, Di Lenarda A, Silvestri F, et al. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart 2001;85:499–504.

797. Kasper EK, Agema WRP, Hutchins GM, Deckers JW, Hare JM, Baughman KL. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol 1994;23:586–590.

798. Grün S, Schumm J, Greulich S, Wagner A, Schneider S, Bruder O, et al. Long-term follow-up of biopsy-proven viral myocarditis. J Am Coll Cardiol 2012;59:1604–1615.

799. Bennett MK, Gilotra NA, Harrington C, Rao S, Dunn JM, Freitag TB, et al. Evaluation of the role of endomyocardial biopsy in 851 patients with unexplained heart failure from 2000–2009. Circ Heart Fail 2013;6:676–684.

800. Schumm J, Greulich S, Wagner A, Grün S, Ong P, Bentz K, et al. Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis. J Cardiovasc Magn Reson 2014;16:14.

801. Russo AD, Casella M, Pieroni M, Pelargonio G, Bartoletti S, Santangeli P, et al. Drug-refractory ventricular tachycardias after myocarditis: endocardial and epicardial radiofrequency catheter ablation. Circ Arrhythm Electrophysiol 2012;5:492–498.

802. Maccabelli G, Tsiachris D, Silberbauer J, Esposito A, Bisceglia C, Baratto F, et al. Imaging and epicardial substrate ablation of ventricular tachycardia in patients late after myocarditis. Europace 2014;16:1363–1372.

803. Berte B, Sacher F, Cochet H, Mahida S, Yamashita S, Lim H, et al. Postmyocarditis ventricular tachycardia in patients with epicardial-only scar: a specific entity requiring a specific approach: epicardial-only VT ablation. J Cardiovasc Electrophysiol 2015; 26:42–50.

804. Maleszewski JJ, Orellana VM, Hodge DO, Kuhl U, Schultheiss H-P, Cooper LT. Long-term risk of recurrence, morbidity and mortality in giant cell myocarditis. Am J Cardiol 2015;115:1733–1738.

805. El-Assaad I, Al-Kindi SG, Oliveira GH, Boyle GJ, Aziz PF. Implantable cardioverterdefibrillator and wait-list outcomes in pediatric patients awaiting heart transplantation. Heart Rhythm 2015;12:2443–2448.

806. Ekström K, Lehtonen J, Kandolin R, Räisänen-Sokolowski A, Salmenkivi K, Kupari M. Long-term outcome and its predictors in giant cell myocarditis: giant cell myocarditis. Eur J Heart Fail 2016;18:1452–1458.

807. Rybicki BA, Iannuzzi MC, Frederick MM, Thompson BW, Rossman MD, Bresnitz EA, et al. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med 2001;164:2085–2091.

808. Muchtar E, Blauwet LA, Gertz MA. Restrictive cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res 2017;121:819–837.

809. Birnie DH, Sauer WH, Bogun F, Cooper JM, Culver DA, Duvernoy CS, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014;11:1304–1323.

810. Birnie DH, Kandolin R, Nery PB, Kupari M. Cardiac manifestations of sarcoidosis: diagnosis and management. Eur Heart J 2016;38:2663–2670.

811. Trivieri MG, Spagnolo P, Birnie D, Liu P, Drake W, Kovacic JC, et al. Challenges in cardiac and pulmonary sarcoidosis: JACC state-of-the-art review. J Am Coll Cardiol 2020;76:1878–1901.

812. Kandolin R, Lehtonen J, Airaksinen J, Vihinen T, Miettinen H, Ylitalo K, et al. Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study. Circulation 2015;131:624–632.

813. Hoogendoorn JC, Sramko M, Venlet J, Siontis KC, Kumar S, Singh R, et al. Electroanatomical voltage mapping to distinguish right-sided cardiac sarcoidosis from arrhythmogenic right ventricular cardiomyopathy. JACC Clin Electrophysiol 2020;6:696–707.

814. Banba K, Kusano KF, Nakamura K, Morita H, Ogawa A, Ohtsuka F, et al. Relationship between arrhythmogenesis and disease activity in cardiac sarcoidosis. Heart Rhythm 2007;4:1292–1299.

815. Takaya Y, Kusano KF, Nakamura K, Ito H. Outcomes in patients with high-degree atrioventricular block as the initial manifestation of cardiac sarcoidosis. Am J Cardiol 2015;115:505–509.

816. Nordenswan H-K, Lehtonen J, Ekström K, Kandolin R, Simonen P, Mäyränpää M, et al. Outcome of cardiac sarcoidosis presenting with high-grade atrioventricular block. Circ Arrhythm Electrophysiol 2018;11.

817. Greulich S, Deluigi CC, Gloekler S, Wahl A, Zürn C, Kramer U, et al. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 2013;6:501–511.

818. Nadel J, Lancefield T, Voskoboinik A, Taylor AJ. Late gadolinium enhancement identified with cardiac magnetic resonance imaging in sarcoidosis patients is associated with long-term ventricular arrhythmia and sudden cardiac death. Eur Heart J Cardiovasc Imaging 2015;16:631–641.

819. Murtagh G, Laffin LJ, Beshai JF, Maffessanti F, Bonham CA, Patel AV, et al. Prognosis of myocardial damage in sarcoidosis patients with preserved left ventricular ejection fraction: risk stratification using cardiovascular magnetic resonance. Circ Cardiovasc Imaging 2016;9:e003738.

820. Ekström K, Lehtonen J, Hänninen H, Kandolin R, Kivistö S, Kupari M. Magnetic resonance imaging as a predictor of survival free of life-threatening arrhythmias and transplantation in cardiac sarcoidosis. J Am Heart Assoc 2016;5:e003040.

821. Coleman GC, Shaw PW, Balfour PC, Gonzalez JA, Kramer CM, Patel AR, et al. Prognostic value of myocardial scarring on CMR in patients with cardiac sarcoidosis. JACC Cardiovasc Imaging 2017;10:411–420.

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823. Mehta D, Mori N, Goldbarg SH, Lubitz S, Wisnivesky JP, Teirstein A. Primary prevention of sudden cardiac death in silent cardiac sarcoidosis: role of programmed ventricular stimulation. Circ Arrhythm Electrophysiol 2011;4:43–48.

824. Okada DR, Smith J, Derakhshan A, Gowani Z, Zimmerman SL, Misra S, et al. Electrophysiology study for risk stratification in patients with cardiac sarcoidosis and abnormal cardiac imaging. Int J Cardiol Heart Vasc 2019;23:100342.

825. Zipse MM, Tzou WS, Schuller JL, Aleong RG, Varosy PD, Tompkins C, et al. Electrophysiologic testing for diagnostic evaluation and risk stratification in patients with suspected cardiac sarcoidosis with preserved left and right ventricular systolic function. J Cardiovasc Electrophysiol 2019;30:1939–1948.

826. Blankstein R, Osborne M, Naya M, Waller A, Kim CK, Murthy VL, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 2014;63:329–336.

827. Crawford T, Mueller G, Sarsam S, Prasitdumrong H, Chaiyen N, Gu X, et al. Magnetic resonance imaging for identifying patients with cardiac sarcoidosis and preserved or mildly reduced left ventricular function at risk of ventricular arrhythmias. Circ Arrhythm Electrophysiol 2014;7:1109–1115.

828. Schuller JL, Zipse M, Crawford T, Bogun F, Beshai J, Patel AR, et al. Implantable cardioverter defibrillator therapy in patients with cardiac sarcoidosis. J Cardiovasc Electrophysiol 2012;23:925–929.

829. Betensky BP, Tschabrunn CM, Zado ES, Goldberg LR, Marchlinski FE, Garcia FC, et al. Long-term follow-up of patients with cardiac sarcoidosis and implantable cardioverter-defibrillators. Heart Rhythm 2012;9:884–891.

830. Kron J, Sauer W, Schuller J, Bogun F, Crawford T, Sarsam S, et al. Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis. EP Europace 2013;15:347–354.

831. Mohsen A, Jimenez A, Hood RE, Dickfeld T, Saliaris A, Shorofsky S, et al. Cardiac sarcoidosis: electrophysiological outcomes on long-term follow-up and the role of the implantable cardioverter-defibrillator. J Cardiovasc Electrophysiol 2014;25: 171–176.

832. Azoulay L-D, Waintraub X, Haroche J, Amoura Z, Cohen Aubart F. Factors associated with implantable cardioverter defibrillators appropriate therapy in cardiac sarcoidosis: a meta-analysis: implantable cardioverter defibrillators in cardiac sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2020;37:17–23.

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833. Smedema J-P, van Geuns R-J, Ector J, Heidbuchel H, Ainslie G, Crijns HJGM. Right ventricular involvement and the extent of left ventricular enhancement with magnetic resonance predict adverse outcome in pulmonary sarcoidosis. ESC Heart Fail 2018;5:157–171.

834. Velangi PS, Chen K-HA, Kazmirczak F, Okasha O, von Wald L, Roukoz H, et al. Right ventricular abnormalities on cardiovascular magnetic resonance imaging in patients with sarcoidosis. JACC Cardiovasc Imaging 2020;13:1395–1405.

835. Ise T, Hasegawa T, Morita Y, Yamada N, Funada A, Takahama H, et al. Extensive late gadolinium enhancement on cardiovascular magnetic resonance predicts adverse outcomes and lack of improvement in LV function after steroid therapy in cardiac sarcoidosis. Heart 2014;100:1165–1172.

836. Yodogawa K, Seino Y, Ohara T, Takayama H, Katoh T, Mizuno K. Effect of corticosteroid therapy on ventricular arrhythmias in patients with cardiac sarcoidosis: effect of corticosteroid therapy. Ann Noninvasive Electrocardiol 2011;16:140–147.

837. Naruse Y, Sekiguchi Y, Nogami A, Okada H, Yamauchi Y, Machino T, et al. Systematic treatment approach to ventricular tachycardia in cardiac sarcoidosis. Circ Arrhythm Electrophysiol 2014;7:407–413.

838. Segawa M, Fukuda K, Nakano M, Kondo M, Satake H, Hirano M, et al. Time course and factors correlating with ventricular tachyarrhythmias after introduction of steroid therapy in cardiac sarcoidosis. Circ Arrhythm Electrophysiol 2016;9:e003353.

839. Kumar S, Barbhaiya C, Nagashima K, Choi E-K, Epstein LM, John RM, et al. Ventricular tachycardia in cardiac sarcoidosis: characterization of ventricular substrate and outcomes of catheter ablation. Circ Arrhythm Electrophysiol 2015;8: 87–93.

840. Muser D, Santangeli P, Liang JJ, Castro SA, Magnani S, Hayashi T, et al. Characterization of the electroanatomic substrate in cardiac sarcoidosis. JACC Clin Electrophysiol 2018;4:291–303.

841. Jefic D, Joel B, Good E, Morady F, Rosman H, Knight B, et al. Role of radiofrequency catheter ablation of ventricular tachycardia in cardiac sarcoidosis: report from a multicenter registry. Heart Rhythm 2009;6:189–195.

842. Papageorgiou N, Providência R, Bronis K, Dechering DG, Srinivasan N, Eckardt L, et al. Catheter ablation for ventricular tachycardia in patients with cardiac sarcoidosis: a systematic review. EP Europace 2018;20:682–691.

843. Siontis KC, Santangeli P, Muser D, Marchlinski FE, Zeppenfeld K, Hoogendoorn JC, et al. Outcomes associated with catheter ablation of ventricular tachycardia in patients with cardiac sarcoidosis. JAMA Cardiol 2022;7:175.

844. Hoogendoorn JC, Venlet J, Out YNJ, Man S, Kumar S, Sramko M, et al. The precordial R’ wave: a novel discriminator between cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy in patients presenting with ventricular tachycardia. Heart Rhythm 2021;18:1539–1547.

845. Bern C. Chagas’ disease. N Engl J Med 2015;373:456–466.

846. Bocchi EA, Bestetti RB, Scanavacca MI, Cunha Neto E, Issa VS. Chronic chagas heart disease management. J Am Coll Cardiol 2017;70:1510–1524.

847. Nunes MCP, Dones W, Morillo CA, Encina JJ, Ribeiro AL. Chagas disease. J Am Coll Cardiol 2013;62:767–776.

848. Nunes MCP, Beaton A, Acquatella H, Bern C, Bolger AF, Echeverría LE, et al. Chagas cardiomyopathy: an update of current clinical knowledge and management: a scientific statement from the American heart association. Circulation 2018;138: e169–e209.

849. Rassi A, Rassi A, Little WC, Xavier SS, Rassi SG, Rassi AG, et al. Development and validation of a risk score for predicting death in Chagas’ heart disease. N Engl J Med 2006;355:799–808.

850. Senra T, Ianni BM, Costa ACP, Mady C, Martinelli-Filho M, Kalil-Filho R, et al. Long-term prognostic value of myocardial fibrosis in patients with chagas cardiomyopathy. J Am Coll Cardiol 2018;72:2577–2587.

851. Rassi FM, Minohara L, Rassi A, Correia LCL, Marin-Neto JA, Rassi A, et al. Systematic review and meta-analysis of clinical outcome after implantable cardioverter-defibrillator therapy in patients with chagas heart disease. JACC Clin Electrophysiol 2019;5:1213–1223.

852. Cardinalli-Neto A, Bestetti RB, Cordeiro JA, Rodrigues VC. Predictors of all-cause mortality for patients with chronic Chagas’ heart disease receiving implantable cardioverter defibrillator therapy. J Cardiovasc Electrophysiol 2007;18:1236–1240.

853. Muratore CA, Batista Sa LA, Chiale PA, Eloy R, Tentori MC, Escudero J, et al. Implantable cardioverter defibrillators and chagas’ disease: results of the ICD registry Latin America. Europace 2008;11:164–168.

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855. Gali WL, Sarabanda AV, Baggio JM, Ferreira LG, Gomes GG, Marin-Neto JA, et al. Implantable cardioverter-defibrillators for treatment of sustained ventricular arrhythmias in patients with chagas’ heart disease: comparison with a control group treated with amiodarone alone. Europace 2014;16:674–680.

856. Carmo AAL, de Sousa MR, Agudelo JF, Boersma E, Rocha MOC, Ribeiro ALP, et al. Implantable cardioverter-defibrillator in chagas heart disease: a systematic review and meta-analysis of observational studies. Int J Cardiol 2018;267:88–93.

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858. Sosa E, Scanavacca M, D’Avila A, Piccioni J, Sanchez O, Velarde JL, et al. Endocardial and epicardial ablation guided by nonsurgical transthoracic epicardial mapping to treat recurrent ventricular tachycardia. J Cardiovasc Electrophysiol 1998;9:229–239.

859. Soto-Becerra R, Bazan V, Bautista W, Malavassi F, Altamar J, Ramirez JD, et al. Ventricular tachycardia in the setting of chagasic cardiomyopathy: use of voltage mapping to characterize endoepicardial nonischemic scar distribution. Circ Arrhythm Electrophysiol 2017;10:e004950.

860. Pisani CF, Romero J, Lara S, Hardy C, Chokr M, Sacilotto L, et al. Efficacy and safety of combined endocardial/epicardial catheter ablation for ventricular tachycardia in chagas disease: a randomized controlled study. Heart Rhythm 2020;17:1510–1518.

861. Chizner MA, Pearle DL, deLeon AC. The natural history of aortic stenosis in adults. Am Heart J 1980;99:419–424.

862. Delahaye JP, Gare JP, Viguier E, Delahaye F, De Gevigney G, Milon H. Natural history of severe mitral regurgitation. Eur Heart J 1991;12:5–9.

863. Groves P. Valve disease: surgery of valve disease: late results and late complications. Heart 2001;86:715–721.

864. Blackstone EH, Kirklin JW. Death and other time-related events after valve replacement. Circulation 1985;72:753–767.

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866. Yang F, Shah B, Iwai S, Markowitz SM, Lerman BB, Stein KM. ICD implantation and arrhythmia-free survival in patients with depressed LV function following surgery for valvular heart disease. Pacing Clin Electrophysiol 2008;31:1419–1424.

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868. Rodríguez-Mañero M, Barrio-López MT, Assi EA, Expósito-García V, Bertomeu-González V, Sánchez-Gómez JM, et al. Primary prevention of sudden death in patients with valvular cardiomyopathy. Rev Esp Cardiol (Engl Ed) 2016; 69:272–278.

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871. Eckart RE, Hruczkowski TW, Tedrow UB, Koplan BA, Epstein LM, Stevenson WG. Sustained ventricular tachycardia associated with corrective valve surgery. Circulation 2007;116:2005–2011.

872. Liang JJ, Castro SA, Muser D, Briceno DF, Shirai Y, Enriquez A, et al. Electrophysiologic substrate, safety, procedural approaches, and outcomes of catheter ablation for ventricular tachycardia in patients after aortic valve replacement. JACC Clin Electrophysiol 2019;5:28–38.

873. Delling FN, Vasan RS. Epidemiology and pathophysiology of mitral valve prolapse: new insights into disease progression, genetics, and molecular basis. Circulation 2014;129:2158–2170.

874. Nalliah CJ, Mahajan R, Elliott AD, Haqqani H, Lau DH, Vohra JK, et al. Mitral valve prolapse and sudden cardiac death: a systematic review and meta-analysis. Heart 2019;105:144–151.

875. Nishimura RA, McGoon MD, Shub C, Miller FA, Ilstrup DM, Tajik AJ. Echocardiographically documented mitral-valve prolapse. Long-term follow-up of 237 patients. N Engl J Med 1985;313:1305–1309.

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877. Sriram CS, Syed FF, Ferguson ME, Johnson JN, Enriquez-Sarano M, Cetta F, et al. Malignant bileaflet mitral valve prolapse syndrome in patients with otherwise idiopathic out-of-hospital cardiac arrest. J Am Coll Cardiol 2013;62:222–230.

878. Kitkungvan D, Nabi F, Kim RJ, Bonow RO, Khan MA, Xu J, et al. Myocardial fibrosis in patients with primary mitral regurgitation with and without prolapse. J Am Coll Cardiol 2018;72:823–834.

879. Nordhues BD, Siontis KC, Scott CG, Nkomo VT, Ackerman MJ, Asirvatham SJ, et al. Bileaflet mitral valve prolapse and risk of ventricular dysrhythmias and death. J Cardiovasc Electrophysiol 2016;27:463–468.

880. Essayagh B, Sabbag A, Antoine C, Benfari G, Yang L-T, Maalouf J, et al. Presentation and outcome of arrhythmic mitral valve prolapse. J Am Coll Cardiol 2020;76: 637–649.

881. Narasimhan C, Jazayeri MR, Sra J, Dhala A, Deshpande S, Biehl M, et al. Ventricular tachycardia in valvular heart disease: facilitation of sustained bundle-branch reentry by valve surgery. Circulation 1997;96:4307–4313.

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882. Moons P, Bovijn L, Budts W, Belmans A, Gewillig M. Temporal trends in survival to adulthood among patients born with congenital heart disease from 1970 to 1992 in Belgium. Circulation 2010;122:2264–2272.

883. Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache M. Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010. Circulation 2014;130:749–756.

884. Koyak Z, Harris L, de Groot JR, Silversides CK, Oechslin EN, Bouma BJ, et al. Sudden cardiac death in adult congenital heart disease. Circulation 2012;126: 1944–1954.

885. Gallego P, Gonzalez AE, Sanchez-Recalde A, Peinado R, Polo L, Gomez-Rubin C, et al. Incidence and predictors of sudden cardiac arrest in adults with congenital heart defects repaired before adult life. Am J Cardiol 2012;110:109–117.

886. Ghai A, Silversides C, Harris L, Webb GD, Siu SC, Therrien J. Left ventricular dysfunction is a risk factor for sudden cardiac death in adults late after repair of tetralogy of Fallot. J Am Coll Cardiol 2002;40:1675–1680.

887. Khairy P, Landzberg MJ, Gatzoulis MA, Lucron H, Lambert J, Marçon F, et al. Value of programmed ventricular stimulation after tetralogy of fallot repair: a multicenter study. Circulation 2004;109:1994–2000.

888. Kapel GFL, Sacher F, Dekkers OM, Watanabe M, Blom NA, Thambo J-B, et al. Arrhythmogenic anatomical isthmuses identified by electroanatomical mapping are the substrate for ventricular tachycardia in repaired tetralogy of Fallot. Eur Heart J 2017;38:268–276.

889. Atallah J, Gonzalez Corcia MC, Walsh EP. Participating members of the pediatric and congenital electrophysiology society. Ventricular arrhythmia and lifethreatening events in patients with repaired tetralogy of Fallot. Am J Cardiol 2020; 132:126–132.

890. Kammeraad JAE, van Deurzen CHM, Sreeram N, Bink-Boelkens MTE, Ottenkamp J, Helbing WA, et al. Predictors of sudden cardiac death after Mustard or Senning repair for transposition of the great arteries. J Am Coll Cardiol 2004;44:1095–1102.

891. Schwerzmann M, Salehian O, Harris L, Siu SC, Williams WG, Webb GD, et al. Ventricular arrhythmias and sudden death in adults after a Mustard operation for transposition of the great arteries. Eur Heart J 2009;30:1873–1879.

892. Miyazaki A, Sakaguchi H, Ohuchi H, Matsuoka M, Komori A, Yamamoto T, et al. Efficacy of hemodynamic-based management of tachyarrhythmia after repair of tetralogy of Fallot. Circ J 2012;76:2855–2862.

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894. Sabate Rotes A, Connolly HM, Warnes CA, Ammash NM, Phillips SD, Dearani JA, et al. Ventricular arrhythmia risk stratification in patients with tetralogy of Fallot at the time of pulmonary valve replacement. Circ Arrhythm Electrophysiol 2015;8: 110–116.

895. Khairy P, Harris L, Landzberg MJ, Fernandes SM, Barlow A, Mercier L-A, et al. Sudden death and defibrillators in transposition of the great arteries with intra-atrial baffles: a multicenter study. Circ Arrhythm Electrophysiol 2008;1:250–257.

896. Roca-Luque I, Rivas Gándara N, Dos Subirà L, Francisco Pascual J, Pérez-Rodon J, Pijuan Domenech A, et al. Intra-atrial re-entrant tachycardia in patients with congenital heart disease: factors associated with disease severity. Europace 2018;20: 1343–1351.

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900. Laredo M, Frank R, Waintraub X, Gandjbakhch E, Iserin L, Hascoët S, et al. Ten-year outcomes of monomorphic ventricular tachycardia catheter ablation in repaired tetralogy of Fallot. Arch Cardiovasc Dis 2017;110:292–302.

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903. Koyak Z, de Groot JR, Bouma BJ, Van Gelder IC, Budts W, Zwinderman AH, et al. Symptomatic but not asymptomatic non-sustained ventricular tachycardia is associated with appropriate implantable cardioverter therapy in tetralogy of Fallot. Int J Cardiol 2013;167:1532–1535.

904. Khairy P, Harris L, Landzberg MJ, Viswanathan S, Barlow A, Gatzoulis MA, et al. Implantable cardioverter-defibrillators in tetralogy of Fallot. Circulation 2008;117: 363–370.

905. Koyak Z, de Groot JR, Van Gelder IC, Bouma BJ, van Dessel PFHM, Budts W, et al. Implantable cardioverter defibrillator therapy in adults with congenital heart disease: who is at risk of shocks? Circ Arrhythm Electrophysiol 2012;5:101–110.

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907. Babu-Narayan SV, Kilner PJ, Li W, Moon JC, Goktekin O, Davlouros PA, et al. Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome. Circulation 2006;113:405–413.

908. Gatzoulis MA, Balaji S, Webber SA, Siu SC, Hokanson JS, Poile C, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet 2000;356:975–981.

909. Bokma JP, Winter MM, Vehmeijer JT, Vliegen HW, van Dijk AP, van Melle JP, et al. QRS fragmentation is superior to QRS duration in predicting mortality in adults with tetralogy of Fallot. Heart 2017;103:666–671.

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915. Visser M, Dooijes D, van der Smagt JJ, van der Heijden JF, Doevendans PA, Loh P, et al. Next-generation sequencing of a large gene panel in patients initially diagnosed with idiopathic ventricular fibrillation. Heart Rhythm 2017;14:1035–1040.

916. Honarbakhsh S, Srinivasan N, Kirkby C, Firman E, Tobin L, Finlay M, et al. Medium-term outcomes of idiopathic ventricular fibrillation survivors and family screening: a multicentre experience. Europace 2017;19:1874–1880.

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918. Conte G, Caputo ML, Regoli F, Marcon S, Klersy C, Adjibodou B, et al. True idiopathic ventricular fibrillation in out-of-hospital cardiac arrest survivors in the Swiss Canton Ticino: prevalence, clinical features, and long-term follow-up. Europace 2017;19:259–266.

919. Stampe NK, Jespersen CB, Glinge C, Bundgaard H, Tfelt-Hansen J, Winkel BG. Clinical characteristics and risk factors of arrhythmia during follow-up of patients with idiopathic ventricular fibrillation. J Cardiovasc Electrophysiol 2020;31: 2677–2686.

920. Conte G, Belhassen B, Lambiase P, Ciconte G, de Asmundis C, Arbelo E, et al. Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry. Europace 2019;21:1670–1677.

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922. Malhi N, Cheung CC, Deif B, Roberts JD, Gula LJ, Green MS, et al. Challenge and impact of quinidine access in sudden death syndromes: a national experience. JACC Clin Electrophysiol 2019;5:376–382.

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924. Belhassen B, Shapira I, Shoshani D, Paredes A, Miller H, Laniado S. Idiopathic ventricular fibrillation: inducibility and beneficial effects of class I antiarrhythmic agents. Circulation 1987;75:809–816.

925. Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990;120: 661–671.

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926. Belhassen B, Viskin S, Fish R, Glick A, Setbon I, Eldar M. Effects of electrophysiologic-guided therapy with Class IA antiarrhythmic drugs on the longterm outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome. J Cardiovasc Electrophysiol 1999;10:1301–1312.

927. Sadek MM, Benhayon D, Sureddi R, Chik W, Santangeli P, Supple GE, et al. Idiopathic ventricular arrhythmias originating from the moderator band: electrocardiographic characteristics and treatment by catheter ablation. Heart Rhythm 2015;12:67–75.

928. Van Herendael H, Zado ES, Haqqani H, Tschabrunn CM, Callans DJ, Frankel DS, et al. Catheter ablation of ventricular fibrillation: importance of left ventricular out-

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929. Santoro F, Di Biase L, Hranitzky P, Sanchez JE, Santangeli P, Perini AP, et al. Ventricular fibrillation triggered by PVCs from papillary muscles: clinical features and ablation. J Cardiovasc Electrophysiol 2014;25:1158–1164.

930. Nakamura T, Schaeffer B, Tanigawa S, Muthalaly RG, John RM, Michaud GF, et al. Catheter ablation of polymorphic ventricular tachycardia/fibrillation in patients with and without structural heart disease. Heart Rhythm 2019;16:1021–1027.

931. Moss AJ, Schwartz PJ, Crampton RS, Tzivoni D, Locati EH, MacCluer J, et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation 1991;84:1136–1144.

932. Schwartz PJ, Ackerman MJ, Antzelevitch C, Bezzina CR, Borggrefe M, Cuneo BF, et al. Inherited cardiac arrhythmias. Nat Rev Dis Primers 2020;6:58.

933. Andersen ED, Krasilnikoff PA, Overvad H. Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome? Acta Paediatr Scand 1971;60:559–564.

934. Tawil R, Ptacek LJ, Pavlakis SG, DeVivo DC, Penn AS, Ozdemir C, et al. Andersen’s syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Ann Neurol 1994;35:326–330.

935. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A 2005;102:8089–8096; discussion 8086–8088.

936. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with

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937. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993;88:782–784.

938. Rautaharju PM, Zhang Z-M, Prineas R, Heiss G. Assessment of prolonged QT and JT intervals in ventricular conduction defects. Am J Cardiol 2004;93:1017–1021.

939. Viskin S, Postema PG, Bhuiyan ZA, Rosso R, Kalman JM, Vohra JK, et al. The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol 2010;55:1955–1961.

940. Mazzanti A, Maragna R, Vacanti G, Monteforte N, Bloise R, Marino M, et al. Interplay between genetic substrate, QTc duration, and arrhythmia risk in patients with long QT syndrome. J Am Coll Cardiol 2018;71:1663–1671.

941. Behr ER, Roden D. Drug-induced arrhythmia: pharmacogenomic prescribing? Eur Heart J 2013;34:89–95.

942. Weeke PE, Kellemann JS, Jespersen CB, Theilade J, Kanters JK, Hansen MS, et al. Long-term proarrhythmic pharmacotherapy among patients with congenital long QT syndrome and risk of arrhythmia and mortality. Eur Heart J 2019;40: 3110–3117.

943. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001;103:89–95.

944. Chockalingam P, Crotti L, Girardengo G, Johnson JN, Harris KM, van der Heijden JF, et al. Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol 2012;60:2092–2099.

945. Ahn J, Kim HJ, Choi J-I, Lee KN, Shim J, Ahn HS, et al. Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: a meta-analysis. PLoS One 2017;12:e0185680.

946. Priori SG, Napolitano C, Schwartz PJ, Grillo M, Bloise R, Ronchetti E, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 2004;292:1341–1344.

947. Mazzanti A, Trancuccio A, Kukavica D, Pagan E, Wang M, Mohsin M, et al. Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk). Europace 2021;24:697–698.

948. Mazzanti A, Maragna R, Faragli A, Monteforte N, Bloise R, Memmi M, et al. Gene-specific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol 2016;67:1053–1058.

949. Ruan Y, Liu N, Bloise R, Napolitano C, Priori SG. Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation 2007;116:1137–1144.

950. Zhu W, Mazzanti A, Voelker TL, Hou P, Moreno JD, Angsutararux P, et al. Predicting patient response to the antiarrhythmic mexiletine based on genetic variation. Circ Res 2019;124:539–552.

951. Priori SG, Napolitano C, Schwartz PJ, Bloise R, Crotti L, Ronchetti E. The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation 2000;102:945–947.

952. Moss AJ, Zareba W, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000;101:616–623.

953. Jons C, Moss AJ, Goldenberg I, Liu J, McNitt S, Zareba W, et al. Risk of fatal arrhythmic events in long QT syndrome patients after syncope. J Am Coll Cardiol 2010;55: 783–788.

954. Liu JF, Jons C, Moss AJ, McNitt S, Peterson DR, Qi M, et al. Risk factors for recurrent syncope and subsequent fatal or near-fatal events in children and adolescents with long QT syndrome. J Am Coll Cardiol 2011;57:941–950.

955. Seth R, Moss AJ, McNitt S, Zareba W, Andrews ML, Qi M, et al. Long QT syndrome and pregnancy. J Am Coll Cardiol 2007;49:1092–1098.

956. Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S, et al. Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. J Am Coll Cardiol 2011;57:51–59.

957. Jang SY, Cho Y, Kim NK, Kim C-Y, Sohn J, Roh J-H, et al. Video-assisted thoracoscopic left cardiac sympathetic denervation in patients with hereditary ventricular arrhythmias. Pacing Clin Electrophysiol 2017;40:232–241.

958. Waddell-Smith KE, Ertresvaag KN, Li J, Chaudhuri K, Crawford JR, Hamill JK, et al. Physical and psychological consequences of left cardiac sympathetic denervation in long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol 2015;8:1151–1158.

959. Anderson HN, Bos JM, Rohatgi RK, Ackerman MJ. The effect of left cardiac sympathetic denervation on exercise in patients with long QT syndrome. JACC Clin Electrophysiol 2019;5:1084–1090.

960. Bos JM, Bos KM, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation in long QT syndrome: analysis of therapeutic nonresponders. Circ Arrhythm Electrophysiol 2013;6:705–711.

961. Bhandari AK, Shapiro WA, Morady F, Shen EN, Mason J, Scheinman MM. Electrophysiologic testing in patients with the long QT syndrome. Circulation 1985;71:63–71.

962. Zareba W, Moss AJ, Daubert JP, Hall WJ, Robinson JL, Andrews M. Implantable cardioverter defibrillator in high-risk long QT syndrome patients. J Cardiovasc Electrophysiol 2003;14:337–341.

963. Schwartz PJ, Spazzolini C, Priori SG, Crotti L, Vicentini A, Landolina M, et al. Who are the long-QT syndrome patients who receive an implantable cardioverterdefibrillator and what happens to them?: Data from the European long-QT syndrome implantable cardioverter-defibrillator (LQTS ICD) registry. Circulation 2010;122:1272–1282.

964. Delannoy E, Sacher F, Maury P, Mabo P, Mansourati J, Magnin I, et al. Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation. Europace 2013;15:1805–1811.

965. Inoue YY, Aiba T, Kawata H, Sakaguchi T, Mitsuma W, Morita H, et al. Different responses to exercise between Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia. Europace 2018;20:1675–1682.

966. Krych M, Biernacka EK, Ponińska J, Kukla P, Filipecki A, Gajda R, et al. Andersen-Tawil syndrome: clinical presentation and predictors of symptomatic arrhythmias—possible role of polymorphisms K897T in KCNH2 and H558R in SCN5A gene. J Cardiol 2017;70:504–510.

967. Mazzanti A, Guz D, Trancuccio A, Pagan E, Kukavica D, Chargeishvili T, et al. Natural history and risk stratification in Andersen-Tawil syndrome type 1. J Am Coll Cardiol 2020;75:1772–1784.

968. Zhang L, Benson DW, Tristani-Firouzi M, Ptacek LJ, Tawil R, Schwartz PJ, et al. Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation 2005;111:2720–2726.

969. Horigome H, Ishikawa Y, Kokubun N, Yoshinaga M, Sumitomo N, Lin L, et al. Multivariate analysis of TU wave complex on electrocardiogram in Andersen-Tawil syndrome with KCNJ2 mutations. Ann Noninvasive Electrocardiol 2020;25:e12721.

970. Miyamoto K, Aiba T, Kimura H, Hayashi H, Ohno S, Yasuoka C, et al. Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations. Heart Rhythm 2015;12:596–603.

971. Radwański PB, Greer-Short A, Poelzing S. Inhibition of Na+ channels ameliorates arrhythmias in a drug-induced model of Andersen-Tawil syndrome. Heart Rhythm 2013;10:255–263.

972. Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, et al. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002;110:381–388.

973. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005;111:659–670.

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974. Savastano S, Rordorf R, Vicentini A, Petracci B, Taravelli E, Castelletti S, et al. A comprehensive electrocardiographic, molecular, and echocardiographic study of Brugada syndrome: validation of the 2013 diagnostic criteria. Heart Rhythm 2014; 11:1176–1183.

975. Richter S, Sarkozy A, Paparella G, Henkens S, Boussy T, Chierchia G-B, et al. Number of electrocardiogram leads displaying the diagnostic coved-type pattern in Brugada syndrome: a diagnostic consensus criterion to be revised. Eur Heart J 2010;31:1357–1364.

976. Veltmann C, Papavassiliu T, Konrad T, Doesch C, Kuschyk J, Streitner F, et al. Insights into the location of type I ECG in patients with Brugada syndrome: correlation of ECG and cardiovascular magnetic resonance imaging. Heart Rhythm 2012; 9:414–421.

977. Adler A, Rosso R, Chorin E, Havakuk O, Antzelevitch C, Viskin S. Risk stratification in Brugada syndrome: clinical characteristics, electrocardiographic parameters, and auxiliary testing. Heart Rhythm 2016;13:299–310.

978. Hasdemir C, Payzin S, Kocabas U, Sahin H, Yildirim N, Alp A, et al. High prevalence of concealed Brugada syndrome in patients with atrioventricular nodal reentrant tachycardia. Heart Rhythm 2015;12:1584–1594.

979. Behr ER, Ben-Haim Y, Ackerman MJ, Krahn AD, Wilde AAM. Brugada syndrome and reduced right ventricular outflow tract conduction reserve: a final common pathway? Eur Heart J 2021;42:1073–1081.

980. Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, et al. Long-term prognosis of patients diagnosed with Brugada syndrome: results from the FINGER Brugada syndrome registry. Circulation 2010;121:635–643.

981. Amin AS, Meregalli PG, Bardai A, Wilde AAM, Tan HL. Fever increases the risk for cardiac arrest in the Brugada syndrome. Ann Intern Med 2008;149:216–218.

982. Adler A, Topaz G, Heller K, Zeltser D, Ohayon T, Rozovski U, et al. Fever-induced Brugada pattern: how common is it and what does it mean? Heart Rhythm 2013;10: 1375–1382.

983. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002;105:1342–1347.

984. Rizzo A, Borio G, Sieira J, Van Dooren S, Overeinder I, Bala G, et al. Ajmaline testing and the Brugada syndrome. Am J Cardiol 2020;135:91–98.

985. Poli S, Toniolo M, Maiani M, Zanuttini D, Rebellato L, Vendramin I, et al. Management of untreatable ventricular arrhythmias during pharmacologic challenges with sodium channel blockers for suspected Brugada syndrome. Europace 2018;20:234–242.

986. Hasdemir C, Juang JJ-M, Kose S, Kocabas U, Orman MN, Payzin S, et al. Coexistence of atrioventricular accessory pathways and drug-induced type 1 Brugada pattern. Pacing Clin Electrophysiol 2018;41:1078–1092.

987. Probst V, Wilde AAM, Barc J, Sacher F, Babuty D, Mabo P, et al. SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet 2009;2:552–557.

988. Meregalli PG, Tan HL, Probst V, Koopmann TT, Tanck MW, Bhuiyan ZA, et al. Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies. Heart Rhythm 2009;6:341–348.

989. Ishikawa T, Kimoto H, Mishima H, Yamagata K, Ogata S, Aizawa Y, et al. Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome. Eur Heart J 2021;42:2854–2863.

990. Gehi AK, Duong TD, Metz LD, Gomes JA, Mehta D. Risk stratification of individuals with the Brugada electrocardiogram: a meta-analysis. J Cardiovasc Electrophysiol 2006;17:577–583.

991. McNamara DA, Goldberger JJ, Berendsen MA, Huffman MD. Implantable defibrillators versus medical therapy for cardiac channelopathies. Cochrane Database Syst Rev 2015;2015:CD011168.

992. Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol 2012;59:37–45.

993. Dereci A, Yap S-C, Schinkel AFL. Meta-analysis of clinical outcome after implantable cardioverter-defibrillator implantation in patients with Brugada syndrome. JACC Clin Electrophysiol 2019;5:141–148.

994. Conte G, Sieira J, Ciconte G, de Asmundis C, Chierchia G-B, Baltogiannis G, et al. Implantable cardioverter-defibrillator therapy in Brugada syndrome: a 20-year single-center experience. J Am Coll Cardiol 2015;65:879–888.

995. Mascia G, Della Bona R, Ameri P, Canepa M, Porto I, Brignole M. Brugada syndrome and syncope: a systematic review. J Cardiovasc Electrophysiol 2020;31:3334–3338.

996. Subramanian M, Prabhu MA, Harikrishnan MS, Shekhar SS, Pai PG, Natarajan K. The utility of exercise testing in risk stratification of asymptomatic patients with type 1 Brugada pattern. J Cardiovasc Electrophysiol 2017;28:677–683.

997. Kubala M, Aïssou L, Traullé S, Gugenheim A-L, Hermida J-S. Use of implantable loop recorders in patients with Brugada syndrome and suspected risk of ventricular arrhythmia. Europace 2012;14:898–902.

998. Sakhi R, Assaf A, Theuns DAMJ, Verhagen JMA, Szili-Torok T, Roos-Hesselink JW, et al. Outcome of insertable cardiac monitors in symptomatic patients with

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999. Scrocco C, Ben-Haim Y, Devine B, Tome-Esteban M, Papadakis M, Sharma S, et al. Role of subcutaneous implantable loop recorder for the diagnosis of arrhythmias in Brugada syndrome: a United Kingdom single-center experience. Heart Rhythm 2022;19:70–78.

1000. Sieira J, Brugada P. Brugada syndrome: defining the risk in asymptomatic patients. Arrhythm Electrophysiol Rev 2016;5:164–169.

1001. Nishizaki M, Sakurada H, Yamawake N, Ueda-Tatsumoto A, Hiraoka M. Low risk for arrhythmic events in asymptomatic patients with drug-induced type 1 ECG. Do patients with drug-induced Brugada type ECG have poor prognosis? (Con). Circ J 2010;74:2464–2473.

1002. Conte G, de Asmundis C, Sieira J, Ciconte G, Di Giovanni G, Chierchia G-B, et al. Prevalence and clinical impact of early repolarization pattern and QRS-fragmentation in high-risk patients with Brugada syndrome. Circ J 2016;80: 2109–2116.

1003. Kataoka N, Mizumaki K, Nakatani Y, Sakamoto T, Yamaguchi Y, Tsujino Y, et al. Paced QRS fragmentation is associated with spontaneous ventricular fibrillation in patients with Brugada syndrome. Heart Rhythm 2016;13:1497–1503.

1004. Probst V, Goronflot T, Anys S, Tixier R, Briand J, Berthome P, et al. Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome. Eur Heart J 2021;42:1687–1695.

1005. Honarbakhsh S, Providencia R, Garcia-Hernandez J, Martin CA, Hunter RJ, Lim WY, et al. A primary prevention clinical risk score model for patients with Brugada syndrome (BRUGADA-RISK). JACC Clin Electrophysiol 2021;7:210–222.

1006. Andorin A, Gourraud J-B, Mansourati J, Fouchard S, le Marec H, Maury P, et al. The QUIDAM study: hydroquinidine therapy for the management of Brugada syndrome patients at high arrhythmic risk. Heart Rhythm 2017;14:1147–1154.

1007. Belhassen B, Rahkovich M, Michowitz Y, Glick A, Viskin S. Management of Brugada syndrome: thirty-three-year experience using electrophysiologically guided therapy with class 1A antiarrhythmic drugs. Circ Arrhythm Electrophysiol 2015;8: 1393–1402.

1008. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, et al. Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation. Heart Rhythm 2007;4:695–700.

1009. Nademanee K, Raju H, de Noronha SV, Papadakis M, Robinson L, Rothery S, et al. Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome. J Am Coll Cardiol 2015;66:1976–1986.

1010. Nademanee K, Haissaguerre M, Hocini M, Nogami A, Cheniti G, Duchateau J, et al. Mapping and ablation of ventricular fibrillation associated with early repolarization syndrome. Circulation 2019;140:1477–1490.

1011. Nademanee K, Veerakul G, Chandanamattha P, Chaothawee L, Ariyachaipanich A, Jirasirirojanakorn K, et al. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation 2011;123:1270–1279.

1012. Zhang P, Tung R, Zhang Z, Sheng X, Liu Q, Jiang R, et al. Characterization of the epicardial substrate for catheter ablation of Brugada syndrome. Heart Rhythm 2016;13:2151–2158.

1013. Haïssaguerre M, Extramiana F, Hocini M, Cauchemez B, Jaïs P, Cabrera JA, et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation 2003;108:925–928.

1014. Brugada J, Pappone C, Berruezo A, Vicedomini G, Manguso F, Ciconte G, et al. Brugada syndrome phenotype elimination by epicardial substrate ablation. Circ Arrhythm Electrophysiol 2015;8:1373–1381.

1015. Pappone C, Brugada J, Vicedomini G, Ciconte G, Manguso F, Saviano M, et al. Electrical substrate elimination in 135 consecutive patients with Brugada syndrome. Circ Arrhythm Electrophysiol 2017;10:e005053.

1016. Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, et al. Genotype-phenotype correlation of SCN5A mutation for the clinical and electrocardiographic characteristics of probands with Brugada syndrome: a Japanese multicenter registry. Circulation 2017;135:2255–2270.

1017. Haïssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358: 2016–2023.

1018. Rosso R, Kogan E, Belhassen B, Rozovski U, Scheinman MM, Zeltser D, et al. J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol 2008;52: 1231–1238.

1019. Macfarlane PW, Antzelevitch C, Haissaguerre M, Huikuri HV, Potse M, Rosso R, et al. The early repolarization pattern: a consensus paper. J Am Coll Cardiol 2015; 66:470–477.

1020. Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA, et al. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009;361:2529–2537.

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1021. Sinner MF, Reinhard W, Müller M, Beckmann B-M, Martens E, Perz S, et al. Association of early repolarization pattern on ECG with risk of cardiac and allcause mortality: a population-based prospective cohort study (MONICA/ KORA). PLoS Med 2010;7:e1000314.

1022. Nunn LM, Bhar-Amato J, Lowe MD, Macfarlane PW, Rogers P, McKenna WJ, et al. Prevalence of J-point elevation in sudden arrhythmic death syndrome families. J Am Coll Cardiol 2011;58:286–290.

1023. Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, et al. Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization. Circ Arrhythm Electrophysiol 2011;4:874–881.

1024. Chauveau S, Janin A, Till M, Morel E, Chevalier P, Millat G. Early repolarization syndrome caused by de novo duplication of KCND3 detected by next-generation sequencing. HeartRhythm Case Rep 2017;3:574–578.

1025. Takayama K, Ohno S, Ding W-G, Ashihara T, Fukumoto D, Wada Y, et al. A de novo gain-of-function KCND3 mutation in early repolarization syndrome. Heart Rhythm 2019;16:1698–1706.

1026. Rosso R, Glikson E, Belhassen B, Katz A, Halkin A, Steinvil A, et al. Distinguishing ‘benign’ from ‘malignant early repolarization’: the value of the ST-segment morphology. Heart Rhythm 2012;9:225–229.

1027. Tikkanen JT, Junttila MJ, Anttonen O, Aro AL, Luttinen S, Kerola T, et al. Early repolarization: electrocardiographic phenotypes associated with favorable longterm outcome. Circulation 2011;123:2666–2673.

1028. Nademanee K, Veerakul G, Mower M, Likittanasombat K, Krittayapong R, Bhuripanyo K, et al. Defibrillator versus beta-blockers for unexplained Death in Thailand (DEBUT): a randomized clinical trial. Circulation 2003;107:2221–2226.

1029. Brugada J, Brugada R, Brugada P. Pharmacological and device approach to therapy of inherited cardiac diseases associated with cardiac arrhythmias and sudden death. J Electrocardiol 2000;33:41–47.

1030. Haïssaguerre M, Sacher F, Nogami A, Komiya N, Bernard A, Probst V, et al. Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization role of drug therapy. J Am Coll Cardiol 2009;53:612–619.

1031. Aizawa Y, Chinushi M, Hasegawa K, Naiki N, Horie M, Kaneko Y, et al. Electrical storm in idiopathic ventricular fibrillation is associated with early repolarization. J Am Coll Cardiol 2013;62:1015–1019.

1032. Patocskai B, Barajas-Martinez H, Hu D, Gurabi Z, Koncz I, Antzelevitch C. Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome. Heart Rhythm 2016;13:1326–1334.

1033. Nam G-B, Kim Y-H, Antzelevitch C. Augmentation of J waves and electrical storms in patients with early repolarization. N Engl J Med 2008;358:2078–2079.

1034. Rodríguez-Capitán J, Fernández-Meseguer A, García-Pinilla JM, Calvo-Bonacho E, Jiménez-Navarro M, García-Margallo T, et al. Frequency of different electrocardiographic abnormalities in a large cohort of Spanish workers. Europace 2017; 19:1855–1863.

1035. Sun G-Z, Ye N, Chen Y-T, Zhou Y, Li Z, Sun Y-X. Early repolarization pattern in the general population: prevalence and associated factors. Int J Cardiol 2017;230: 614–618.

1036. Wu S-H, Lin X-X, Cheng Y-J, Qiang C-C, Zhang J. Early repolarization pattern and risk for arrhythmia death: a meta-analysis. J Am Coll Cardiol 2013;61:645–650.

1037. Malhi N, So PP, Cheung CC, Laksman ZWM, Healey JS, Chauhan VS, et al. Early repolarization pattern inheritance in the cardiac arrest survivors with preserved ejection fraction registry (CASPER). JACC Clin Electrophysiol 2018;4:1473–1479.

1038. Sinner MF, Porthan K, Noseworthy PA, Havulinna AS, Tikkanen JT, Müller-Nurasyid M, et al. A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern. Heart Rhythm 2012;9: 1627–1634.

1039. Adhikarla C, Boga M, Wood AD, Froelicher VF. Natural history of the electrocardiographic pattern of early repolarization in ambulatory patients. Am J Cardiol 2011;108:1831–1835.

1040. Mahida S, Derval N, Sacher F, Leenhardt A, Deisenhofer I, Babuty D, et al. Role of electrophysiological studies in predicting risk of ventricular arrhythmia in early repolarization syndrome. J Am Coll Cardiol 2015;65:151–159.

1041. Aizawa Y, Sato A, Watanabe H, Chinushi M, Furushima H, Horie M, et al. Dynamicity of the J-wave in idiopathic ventricular fibrillation with a special reference to pause-dependent augmentation of the J-wave. J Am Coll Cardiol 2012;59: 1948–1953.

1042. Priori SG, Mazzanti A, Santiago DJ, Kukavica D, Trancuccio A, Kovacic JC. Precision medicine in catecholaminergic polymorphic ventricular tachycardia: JACC focus seminar 5/5. J Am Coll Cardiol 2021;77:2592–2612.

1043. Bezzina CR, Lahrouchi N, Priori SG. Genetics of sudden cardiac death. Circ Res 2015;116:1919–1936.

1044. Kimura H, Zhou J, Kawamura M, Itoh H, Mizusawa Y, Ding W-G, et al. Phenotype variability in patients carrying KCNJ2 mutations. Circ Cardiovasc Genet 2012;5: 344–353.

1045. Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, Gasparini M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002;106:69–74.

1046. Krahn AD, Gollob M, Yee R, Gula LJ, Skanes AC, Walker BD, et al. Diagnosis of unexplained cardiac arrest: role of adrenaline and procainamide infusion. Circulation 2005;112:2228–2234.

1047. Hayashi M, Denjoy I, Extramiana F, Maltret A, Buisson NR, Lupoglazoff J-M, et al. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 2009;119:2426–2434.

1048. Leren IS, Saberniak J, Majid E, Haland TF, Edvardsen T, Haugaa KH. Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2016;13:433–440.

1049. Peltenburg PJ, Kallas D, Bos JM, Lieve KVV, Franciosi S, Roston TM, et al. An international multicenter cohort study on β-blockers for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia. Circulation 2022;145:333–344.

1050. van der Werf C, Nederend I, Hofman N, van Geloven N, Ebink C, Frohn-Mulder IME, et al. Familial evaluation in catecholaminergic polymorphic ventricular tachycardia: disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives. Circ Arrhythm Electrophysiol 2012;5:748–756.

1051. Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, et al. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med 2009;15:380–383.

1052. Wang G, Zhao N, Zhong S, Wang Y, Li J. Safety and efficacy of flecainide for patients with catecholaminergic polymorphic ventricular tachycardia: a systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e16961.

1053. van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, et al. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol 2011;57:2244–2254.

1054. Padfield GJ, AlAhmari L, Lieve KVV, AlAhmari T, Roston TM, Wilde AA, et al. Flecainide monotherapy is an option for selected patients with catecholaminergic polymorphic ventricular tachycardia intolerant of β-blockade. Heart Rhythm 2016; 13:609–613.

1055. Roses-Noguer F, Jarman JWE, Clague JR, Till J. Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2014;11: 58–66.

1056. De Ferrari GM, Dusi V, Spazzolini C, Bos JM, Abrams DJ, Berul CI, et al. Clinical management of catecholaminergic polymorphic ventricular tachycardia: the role of left cardiac sympathetic denervation. Circulation 2015;131:2185–2193.

1057. Roston TM, Jones K, Hawkins NM, Bos JM, Schwartz PJ, Perry F, et al. Implantable cardioverter-defibrillator use in catecholaminergic polymorphic ventricular tachycardia: a systematic review. Heart Rhythm 2018;15:1791–1799.

1058. van der Werf C, Lieve KV, Bos JM, Lane CM, Denjoy I, Roses-Noguer F, et al. Implantable cardioverter-defibrillators in previously undiagnosed patients with catecholaminergic polymorphic ventricular tachycardia resuscitated from sudden cardiac arrest. Eur Heart J 2019;40:2953–2961.

1059. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 1995;91:1512–1519.

1060. Kannankeril PJ, Moore JP, Cerrone M, Priori SG, Kertesz NJ, Ro PS, et al. Efficacy of flecainide in the treatment of catecholaminergic polymorphic ventricular tachycardia: a randomized clinical trial. JAMA Cardiol 2017;2:759–766.

1061. Gollob MH, Redpath CJ, Roberts JD. The short QT syndrome: proposed diagnostic criteria. J Am Coll Cardiol 2011;57:802–812.

1062. Thorsen K, Dam VS, Kjaer-Sorensen K, Pedersen LN, Skeberdis VA, Jurevičius J, et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nat Commun 2017;8:1696.

1063. Mazzanti A, Kanthan A, Monteforte N, Memmi M, Bloise R, Novelli V, et al. Novel insight into the natural history of short QT syndrome. J Am Coll Cardiol 2014;63: 1300–1308.

1064. Dhutia H, Malhotra A, Parpia S, Gabus V, Finocchiaro G, Mellor G, et al. The prevalence and significance of a short QT interval in 18 825 low-risk individuals including athletes. Br J Sports Med 2016;50:124–129.

1065. Gallagher MM, Magliano G, Yap YG, Padula M, Morgia V, Postorino C, et al. Distribution and prognostic significance of QT intervals in the lowest half centile in 12,012 apparently healthy persons. Am J Cardiol 2006;98:933–935.

1066. Anttonen O, Junttila MJ, Rissanen H, Reunanen A, Viitasalo M, Huikuri HV. Prevalence and prognostic significance of short QT interval in a middle-aged Finnish population. Circulation 2007;116:714–720.

1067. Kobza R, Roos M, Niggli B, Abächerli R, Lupi GA, Frey F, et al. Prevalence of long and short QT in a young population of 41,767 predominantly male Swiss conscripts. Heart Rhythm 2009;6:652–657.

1068. Giustetto C, Schimpf R, Mazzanti A, Scrocco C, Maury P, Anttonen O, et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol 2011;58:587–595.

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1069. El-Battrawy I, Besler J, Liebe V, Schimpf R, Tülümen E, Rudic B, et al. Long-term follow-up of patients with short QT syndrome: clinical profile and outcome. J Am Heart Assoc 2018;7:e010073.

1070. Mazzanti A, Maragna R, Vacanti G, Kostopoulou A, Marino M, Monteforte N, et al. Hydroquinidine prevents life-threatening arrhythmic events in patients with short QT syndrome. J Am Coll Cardiol 2017;70:3010–3015.

1071. El-Battrawy I, Besler J, Li X, Lan H, Zhao Z, Liebe V, et al. Impact of antiarrhythmic drugs on the outcome of short QT syndrome. Front Pharmacol 2019;10:771.

1072. Malik M. Drug-induced QT/QTc interval shortening: lessons from drug-induced QT/QTc prolongation. Drug Saf 2016;39:647–659.

1073. Giustetto C, Scrocco C, Schimpf R, Maury P, Mazzanti A, Levetto M, et al. Usefulness of exercise test in the diagnosis of short QT syndrome. Europace 2015;17:628–634.

1074. Mason JW, Ramseth DJ, Chanter DO, Moon TE, Goodman DB, Mendzelevski B. Electrocardiographic reference ranges derived from 79,743 ambulatory subjects. J Electrocardiol 2007;40:228–234.

1075. Bun S-S, Maury P, Giustetto C, Deharo J-C. Electrical storm in short-QT syndrome successfully treated with Isoproterenol. J Cardiovasc Electrophysiol 2012; 23:1028–1030.

1076. Siu SC, Sermer M, Colman JM, Alvarez AN, Mercier LA, Morton BC, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515–521.

1077. Drenthen W, Pieper PG, Roos-Hesselink JW, van Lottum WA, Voors AA, Mulder BJM, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007;49:2303–2311.

1078. Roos-Hesselink JW, Ruys TPE, Stein JI, Thilén U, Webb GD, Niwa K, et al. Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology. Eur Heart J 2013;34: 657–665.

1079. Linde C, Bongiorni MG, Birgersdotter-Green U, Curtis AB, Deisenhofer I, Furokawa T, et al. Sex differences in cardiac arrhythmia: a consensus document of the European Heart Rhythm Association, endorsed by the Heart Rhythm Society and Asia Pacific Heart Rhythm Society. Europace 2018;20:1565–1565ao.

1080. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018;39:3165–3241.

1081. Silversides CK, Harris L, Haberer K, Sermer M, Colman JM, Siu SC. Recurrence rates of arrhythmias during pregnancy in women with previous tachyarrhythmia and impact on fetal and neonatal outcomes. Am J Cardiol 2006;97:1206–1212.

1082. Sliwa K, Mebazaa A, Hilfiker-Kleiner D, Petrie MC, Maggioni AP, Laroche C, et al. Clinical characteristics of patients from the worldwide registry on peripartum cardiomyopathy (PPCM): EURObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on PPCM. Eur J Heart Fail 2017;19:1131–1141.

1083. Ware JS, Li J, Mazaika E, Yasso CM, DeSouza T, Cappola TP, et al. Shared genetic predisposition in peripartum and dilated cardiomyopathies. N Engl J Med 2016; 374:233–241.

1084. Wang Y-C, Chen C-H, Su H-Y, Yu M-H. The impact of maternal cardioversion on fetal haemodynamics. Eur J Obstet Gynecol Reprod Biol 2006;126:268–269.

1085. Barnes EJ, Eben F, Patterson D. Direct current cardioversion during pregnancy should be performed with facilities available for fetal monitoring and emergency caesarean section. BJOG 2002;109:1406–1407.

1086. Miyoshi T, Kamiya CA, Katsuragi S, Ueda H, Kobayashi Y, Horiuchi C, et al. Safety and efficacy of implantable cardioverter-defibrillator during pregnancy and after delivery. Circ J 2013;77:1166–1170.

1087. Abello M, Peinado R, Merino JL, Gnoatto M, Mateos M, Silvestre J, et al. Cardioverter defibrillator implantation in a pregnant woman guided with transesophageal echocardiography. Pacing Clin Electrophysiol 2003;26:1913–1914.

1088. Hartz J, Clark BC, Ito S, Sherwin ED, Berul CI. Transvenous nonfluoroscopic pacemaker implantation during pregnancy guided by 3-dimensional electroanatomic mapping. HeartRhythm Case Rep 2017;3:490–492.

1089. Bauersachs J, König T, van der Meer P, Petrie MC, Hilfiker-Kleiner D, Mbakwem A, et al. Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail 2019; 21:827–843.

1090. Duncker D, König T, Hohmann S, Bauersachs J, Veltmann C. Avoiding untimely implantable cardioverter/defibrillator implantation by intensified heart failure therapy optimization supported by the wearable cardioverter/defibrillator-the PROLONG study. J Am Heart Assoc 2017;6:e004512.

1091. Duncker D, Westenfeld R, Konrad T, Pfeffer T, Correia de Freitas CA, Pfister R, et al. Risk for life-threatening arrhythmia in newly diagnosed peripartum cardiomyopathy with low ejection fraction: a German multi-centre analysis. Clin Res Cardiol 2017;106:582–589.

1092. Jeejeebhoy FM, Zelop CM, Lipman S, Carvalho B, Joglar J, Mhyre JM, et al. Cardiac arrest in pregnancy: a scientific statement from the American heart association. Circulation 2015;132:1747–1773.

1093. European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the task force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011;32:3147–3197.

1094. Rashba EJ, Zareba W, Moss AJ, Hall WJ, Robinson J, Locati EH, et al. Influence of pregnancy on the risk for cardiac events in patients with hereditary long QT syndrome. LQTS investigators. Circulation 1998;97:451–456.

1095. Ishibashi K, Aiba T, Kamiya C, Miyazaki A, Sakaguchi H, Wada M, et al. Arrhythmia risk and β-blocker therapy in pregnant women with long QT syndrome. Heart 2017;103:1374–1379.

1096. Cheung CC, Lieve KV, Roston TM, van der Ree MH, Deyell MW, Andrade JG, et al. Pregnancy in catecholaminergic polymorphic ventricular tachycardia. JACC Clin Electrophysiol 2019;5:387–394.

1097. Wu L, Liang E, Fan S, Zheng L, Hu F, Liu S, et al. Effect of pregnancy in arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 2020;125:613–617.

1098. Bauce B, Daliento L, Frigo G, Russo G, Nava A. Pregnancy in women with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Eur J Obstet Gynecol Reprod Biol 2006;127:186–189.

1099. Gandjbakhch E, Varlet E, Duthoit G, Fressart V, Charron P, Himbert C, et al. Pregnancy and newborn outcomes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Int J Cardiol 2018;258:172–178.

1100. Rodríguez-Mañero M, Casado-Arroyo R, Sarkozy A, Leysen E, Sieira JA, Namdar M, et al. The clinical significance of pregnancy in Brugada syndrome. Rev Esp Cardiol (Engl Ed) 2014;67:176–180.

1101. Benito B, Berruezo A. Brugada syndrome and pregnancy: delving into the role of sex hormones in ion channelopathies. Rev Esp Cardiol (Engl Ed) 2014;67:165–167.

1102. Ostrowska B, Kommata B, Malmborg H, Lundqvist CB. Arrhythmias in pregnancy. ESC CardioMed. 3rd ed. Oxford University Press; 2022, p2868–2870.

1103. Sliwa K, Blauwet L, Tibazarwa K, Libhaber E, Smedema J-P, Becker A, et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. Circulation 2010;121:1465–1473.

1104. Hilfiker-Kleiner D, Haghikia A, Berliner D, Vogel-Claussen J, Schwab J, Franke A, et al. Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study. Eur Heart J 2017;38:2671–2679.

1105. Driver K, Chisholm CA, Darby AE, Malhotra R, Dimarco JP, Ferguson JD. Catheter ablation of arrhythmia during pregnancy. J Cardiovasc Electrophysiol 2015;26:698–702.

1106. Wang Z, Chen YW, Jiang YH, Sun LP, Chen XJ, Tao HL, et al. Electrophysiological characteristics and therapeutic efficacy of radiofrequency ablation of focal atrial tachycardia originating from the right atrial appendage during pregnancy. Zhonghua Xin Xue Guan Bing Za Zhi 2020;48:859–865.

1107. Tuzcu V, Kilinc OU. Implantable cardioverter defibrillator implantation without using fluoroscopy in a pregnant patient. Pacing Clin Electrophysiol 2012;35: e265–266.

1108. Fröhlich GM, Holzmeister J, Hübler M, Hübler S, Wolfrum M, Enseleit F, et al. Prophylactic implantable cardioverter defibrillator treatment in patients with endstage heart failure awaiting heart transplantation. Heart 2013;99:1158–1165.

1109. Sandner SE, Wieselthaler G, Zuckermann A, Taghavi S, Schmidinger H, Pacher R, et al. Survival benefit of the implantable cardioverter-defibrillator in patients on the waiting list for cardiac transplantation. Circulation 2001;104:I171–176.

1110. Algalarrondo V, Perault R, Bories M-C, Narayanan K, Garcia R, Combes N, et al. Prophylactic implantable cardioverter defibrillators for primary prevention: From implantation to heart transplantation. Arch Cardiovasc Dis 2018;111:758–765.

1111. Cantero-Pérez EM, Sobrino-Márquez JM, Grande-Trillo A, Lage-Gallé E, Rangel-Sousa D, Esteve-Ruiz IM, et al. Implantable cardioverter defibrillator for primary prevention in patients with severe ventricular dysfunction awaiting heart transplantation. Transplant Proc 2013;45:3659–3661.

1112. Pezawas T, Grimm M, Ristl R, Kivaranovic D, Moser FT, Laufer G, et al. Primary preventive cardioverter-defibrillator implantation (Pro-ICD) in patients awaiting heart transplantation. A prospective, randomized, controlled 12-year follow-up study. Transpl Int 2015;28:34–41.

1113. Kao AC, Krause SW, Handa R, Karia D, Reyes G, Bianco NR, et al. Wearable defibrillator use in heart failure (WIF): results of a prospective registry. BMC Cardiovasc Disord 2012;12:123.

1114. Alba AC, Foroutan F, Hing NKVNF, Fan C-PS, Manlhiot C, Ross HJ. Incidence and predictors of sudden cardiac death after heart transplantation: a systematic review and meta-analysis. Clin Transplant 2018;32:e13206.

1115. Vakil K, Taimeh Z, Sharma A, Abidi KS, Colvin M, Luepker R, et al. Incidence, predictors, and temporal trends of sudden cardiac death after heart transplantation. Heart Rhythm 2014;11:1684–1690.

1116. Alba AC, Fan C-PS, Manlhiot C, Dipchand AI, Stehlik J, Ross HJ. The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT thoracic transplant registry. Clin Transplant 2019;33:e13490.

1117. Eskander MA, Adler E, Hoffmayer KS. Arrhythmias and sudden cardiac death in post-cardiac transplant patients. Curr Opin Cardiol 2020;35:308–311.

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1119. Klein HU, Meltendorf U. Bridging a temporary high risk of sudden arrhythmic death. Experience with the wearable cardioverter defibrillator. PACE 2010;33: 353–367.

1120. Corrado D, Zorzi A. Sudden death in athletes. Int J Cardiol 2017;237:67–70.

1121. Rajan D, Garcia R, Svane J, Tfelt-Hansen J. Risk of sports-related sudden cardiac death in women. Eur Heart J 2021;43:1198–1206.

1122. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998;339:364–369.

1123. Malhotra A, Dhutia H, Finocchiaro G, Gati S, Beasley I, Clift P, et al. Outcomes of cardiac screening in adolescent soccer players. N Engl J Med 2018;379:524–534.

1124. Corrado D, Pelliccia A, Bjørnstad HH, Vanhees L, Biffi A, Borjesson M, et al. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005;26:516–524.

1125. Corrado D, Schmied C, Basso C, Borjesson M, Schiavon M, Pelliccia A, et al. Risk of sports: do we need a pre-participation screening for competitive and leisure athletes? Eur Heart J 2011;32:934–944.

1126. Baggish AL, Hutter AM, Wang F, Yared K, Weiner RB, Kupperman E, et al. Cardiovascular screening in college athletes with and without electrocardiography: a cross-sectional study. Ann Intern Med 2010;152:269–275.

1127. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006;296:1593–1601.

1128. Sharma S, Estes NAM, Vetter VL, Corrado D. Clinical decisions. Cardiac screening before participation in sports. N Engl J Med 2013;369:2049–2053.

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