Exercise Stress Testing (Exercise ECG)
ecgwaves.com · The ECG Book
Chapter 1: Introduction to exercise stress testing (treadmill test, exercise ECG)
Exercise stress testing has been used routinely for over 60 years to evaluate cardiopulmonary function and to diagnose cardiovascular disease. The value of exercise stress testing is evident from the fact that exercise capacity (cardiopulmonary capacity) is one of the strongest predictors of cardiovascular and overall mortality. Thus, the clinical utility of exercise stress testing is immense and the procedure may be used in numerous situations, ranging from health screening to assessment of symptoms after coronary artery bypass surgery. Traditionally, the most common indication for exercise stress testing has been the diagnostic evaluation of coronary artery disease. However, current guidelines (ESC, AHA, ACC) discourage the use of exercise stress testing for the evaluation of coronary artery disease, which is due to the low sensitivity of the method (details below). Sensitivity and specificity are considerably higher for CT angiography, SPECT, echocardiography, and coronary angiography, which are therefore the recommended modalities for the evaluation of coronary artery disease (refer to Evaluation of coronary artery disease and angina pectoris). Yet, exercise stress testing provides a fundamental parameter that cannot be obtained by other imaging methods, namely exercise capacity (and VO2max, see below). In addition to exercise capacity, stress testing also provides information on electrocardiographic (ECG) reaction, the occurrence of arrhythmias, symptoms, physiological reactions (blood pressure, heart rate) during and after exercise, etc.
Exercise stress testing may also be referred to as exercise ECG or exercise tolerance test. Because the vast majority of all exercise stress tests in the United States are performed using a treadmill, the term treadmill test has almost become synonymous with the exercise stress test. However, the term treadmill test should only be used when referring to exercise stress tests carried out on a treadmill. In many parts of the world, the bicycle is preferred over the treadmill, as will be discussed later.
Role of the electrocardiogram (ECG) in exercise stress testing
It is a common misunderstanding that the ECG is the main parameter of the stress test. The ECG reaction is indeed important but several other parameters are equally important. In fact, a large body of evidence demonstrates that the strongest predictor of cardiovascular and overall mortality is maximal (peak) oxygen uptake, which is a measure of cardiovascular fitness and exercise capacity. In clinical practice, however, it is difficult to achieve peak oxygen uptake because it requires maximal exertion, which patients rarely achieve. Patients are usually limited by leg fatigue, discomfort, cardiovascular disease, lack of motivation, etc. Moreover, measuring peak oxygen uptake is technically arduous and therefore peak work intensity is used as a proxy for peak oxygen uptake. This is discussed in detail below.
The purpose of the exercise stress test is to induce cardiovascular stress in order to provoke symptoms, ECG changes, blood pressure response, and heart rate response, as well as assess limiting determinants of exercise capacity. These parameters offer diagnostic and prognostic information which can only be obtained during physical exercise.
Independent of other traditional risk factors, exercise capacity is one of the single best predictors of risk for future adverse events in virtually all patient populations, including apparently healthy individuals.
Exercise stress testing in the age of non-invasive cardiovascular imaging
Advances in computerized tomography (CT), cardiac magnetic resonance imaging (cMRI), and echocardiography have enabled detailed functional and anatomical imaging of cardiac anatomy, assessment of coronary artery stenosis, and myocardial ischemia. These methods offer greater sensitivity and specificity as compared with exercise stress testing. Hence, the exercise stress test is no longer the preferred modality for the evaluation of suspected coronary artery disease. However, exercise stress testing is cheap, widely available, and not dependent on the examiner, it does not confer harmful radiation and provides numerous other parameters that can improve cardiovascular assessment and prognostication. Stress testing also allows for the assessment of the effect of interventions and medications. Furthermore, the exercise stress test provides information on the limiting determinants of exercise capacity (discussed below). The exercise stress test remains one of the most important diagnostic instruments in medicine.
Table 1. Sensitivity and specificity of various modalities to assess coronary artery disease.
| Modality | Sensitivity (%) | Specificity (%) |
|---|---|---|
| Exercise stress testing (exercise ECG) | 40-50% | 85-90% |
| Stress echocardiography | 80-85% | 80-88% |
| Stress SPECT | 73-92% | 63-87% |
| Stress echocardiography with dobutamine | 79-83% | 82-86% |
| Stress MRI with dobutamine | 72-79% | 81-91% |
| Stress echocardiography with vasodilator | 90-91% | 75-84% |
| Stress SPECT with vasodilator | 67-94% | 61-85% |
| CTA coronary artery | 95-99% | 64-83% |
| Stress PET with vasodilator | 91-97% | 74-91% |
Purpose of exercise stress testing
Although exercise stress testing is almost synonymous with the assessment of coronary artery disease, the procedure can be used for several other purposes, as follows:
Assessment of cardiovascular risk.
Detection of coronary artery disease (ischemic heart disease). Individuals with chest pain (or other symptoms suggestive of myocardial ischemia) can be evaluated using exercise stress testing, although sensitivity is considerably higher with other modalities (Table 1).
Evaluation of coronary artery disease. Individuals with known ischemic heart disease frequently perform stress tests as part of risk stratification, assessment of functional capacity, limiting determinants, symptoms, and ECG changes. Repeated stress tests are valuable to follow the course of the disease and allow for tailoring patient management.
Assessment of therapeutic response. Exercise testing can be used to evaluate the effect of medications or interventions such as PCI (percutaneous coronary intervention), CABG (coronary artery bypass grafting), CRT (Cardiac Resynchronization Therapy), etc. The purpose of the exercise test is to evaluate whether such interventions have reduced the intensity or frequency of symptoms or other abnormal signs (e.g. arrhythmias).
Assessment of perioperative risk for noncardiac surgery: Exercise testing is used routinely to assess perioperative risk indirectly by measuring the cardiovascular response, symptoms, and ECG reaction during exercise.
Exercise prescription: For some patients, it may be necessary to evaluate functional capacity and exercise response before prescribing exercise. The purpose of the exercise test is to detect significant symptoms and abnormal cardiovascular responses at various levels of intensity. This allows for setting an appropriate level of exercise intensity.
Determine degree of disability: Exercise stress testing may be used to determine the degree of disability in patients with cardiovascular disease.
Nevertheless, the vast majority of patients referred to exercise stress testing are patients with suspected ischemic heart disease.
Cardiopulmonary exercise stress test (ergospirometry)
Cardiopulmonary exercise testing (CPET, ergospirometry) provides an assessment of the integrative exercise responses involving the pulmonary, musculoskeletal, and cardiovascular systems. This allows for a more comprehensive assessment of these three organ systems. CPET is non-invasive but technically more arduous than traditional exercise stress testing. The use of CPET has increased steadily in the past few decades. The pulmonary measure of main interest is the gas exchange, which is analyzed continuously during the exercise. By analyzing oxygen levels, carbon dioxide levels, respiratory volumes, respiratory frequency, and oxygen uptake, it is possible to estimate cardiac output and peak oxygen uptake, which is the best measure of exercise capacity. Ergospirometry is frequently used for prognostication of heart failure and pulmonary disease.
Safety of exercise stress testing
Exercise testing is a safe procedure. Over six decades of experience and research testify that the risk of complications is very low. It is estimated that approximately 1 death and 2 acute myocardial infarctions are caused per 10,000 tests performed. These estimates vary slightly in different studies, depending on the characteristics of the patient population.
Although exercise testing should not be directly compared with long-distance running, due to differences in the type of workload and the health condition of the participants, it could be interesting to compare the mortality in these two situations. Approximately 1 in 184,000 participants in long-distance races experience a sudden cardiac arrest (JH Kim et al). It follows that the risk is roughly 18 times higher during exercise stress testing. This figure should be viewed in light of the differences in age, risk factors, coexisting conditions, etc, between those performing exercise tests and those performing a marathon.
Indeed, the risk associated with performing an exercise test is very small. The risk that exists is presumably explained by the hazard of provoking myocardial ischemia. Briefly, myocardial ischemia may induce ventricular tachycardia which may degenerate into ventricular fibrillation and cardiac arrest. The risk of ventricular tachycardia depends on the extent of the ischemia (transmural ischemia brings about a great risk of ventricular tachycardia, as compared with subendocardial ischemia which is less hazardous).
Despite the safety of stress testing, patients must be selected with care in order to minimize risk and maximize the usefulness of the procedure.
Selection of patients
The exercise stress test was previously the first choice in patients with suspected ischemic heart disease if the probability of disease was intermediate. The usefulness of the test depends on the patient’s probability of actually having ischemic heart disease. One should therefore begin by assessing the patient’s probability of having ischemic heart disease. This approach is referred to as a Bayesian approach, named after the statistician Thomas Bayes. The Bayesian approach states that the probability that the test will reveal disease depends on the patient’s risk of actually having the disease. This is also referred to as pre-test probability. The pre-test probability depends on risk factors such as age, sex, symptoms, cholesterol levels, smoking status, diabetes status, dietary habits, and so on. Assessing all these variables can be quite cumbersome, which is why the European Society for Cardiology (ESC) suggests are more pragmatic assessment including only age, sex, and symptoms. These three variables are sufficient to estimate a pre-test probability. This will be discussed in detail below.
Thus, pre-test probability is fundamental to assess before referring patients to exercise ECG. It is also important that the patient is capable of performing the test. All patients are not capable of walking on a treadmill, or bicycling, while other patients are not capable of following instructions or communicating verbally. Patients with rheumatic conditions, amputations, severe claudication, etc, may also have difficulties performing the test. These factors must also be taken into consideration.
It is also important to assess whether there are changes in the resting ECG which may impair the evaluation of the ECG reaction during the test.
Changes on the resting ECG which impair the evaluation of the ECG reaction during exercise
The presence of significant ST-T changes on the resting ECG may impair the evaluation of the ECG reaction during exercise. With respect to the ECG, the purpose of the exercise test is to provoke ischemic ECG changes (ST segment depressions). However, there are several conditions that cause ST-T changes (including ST depressions) on the resting ECG and the presence of such will generally make ECG interpretation during exercise more difficult. For example, some conditions may cause ST-T changes which both simulate and mask ischemic ECG changes. The most obvious example is left bundle branch block (LBBB), which causes marked secondary ST-T changes (including ST elevation, ST depression and T-wave inversion) and also masks ischemic ST-T changes. Hence, patients with left bundle branch block on resting ECG should generally not be referred for exercise ECG.
Patients using digoxin (digitalis) may also display significant ST-T changes, particularly ST depressions, on the resting ECG. Such ST depressions are usually generalized, meaning that they are evident in most ECG leads. Digoxin should be withheld 24 hours before exercise testing.
Patients with pre-excitation (Wolff-Parkinson-White syndrome) with delta waves on the resting ECG may not be suitable for exercise ECG. Delta waves are usually associated with secondary ST-T changes which may also impair the ECG interpretation of ischemia.
Patients with pacemakers always display secondary ST-T changes which also renders ischemia detection very difficult. Patients with pacemakers are not suitable for exercise ECG.
Patients with left ventricular hypertrophy (LVH) may display secondary ST-T changes with ST elevations (V1, V2) and ST depressions (V5, V6, aVL, I). The ST depressions may exceed 1 mm on the resting ECG, which renders the exercise test less useful for detecting ischemia. If, however, the ST depressions are less than 1 mm, the exercise test may be useful.
There are also patients with ST segment depressions on the resting ECG without any obvious explanation. As a general rule, if the ST depressions are <1 mm, then the exercise test may be useful.
If any of the above suggests that exercise testing may not serve the patient well, it is recommended that other modalities be selected instead.
Note that right bundle branch block (RBBB) does not interfere with the detection of ischemia; i.e. it is fully possible to detect ischemia in the presence of a right bundle branch block. Readers familiar with the appearance of RBBB may know that it is associated with ST depressions (in the J-60 point) in leads V1–V3, but this is rarely a problem since, in the case of myocardial ischemia, ST depressions are rarely confined to V1–V3 because depressions are virtually always seen in V4–V6 as well.
Pre-test probability: selecting appropriate patients
Although exercise stress testing is no longer recommended for the evaluation of coronary artery disease, the rationale for pre-test probability is still relevant to discuss.
As mentioned above, pre-test probability is the likelihood that the patient has coronary artery disease based on symptoms, age and sex. These three variables are strong predictors of coronary artery disease and they are also readily available. The pre-test probability is related to Bayes’ theorem (Thomas Bayes, 1701–1761). This theorem states that the probability of an event is related to circumstances that are associated with the event. In this scenario, the probability of coronary artery disease will be related to age, sex and symptoms. Pre-test probability is easy to assess and it must always be assessed. The purpose of the pre-test probability is as follows:
Identify patients with a very low probability of disease: these patients most likely do not have the disease and therefore the test is not particularly useful. Furthermore, if they had the disease, it is likely that the disease is very mild and the test will therefore not be able to detect it.
Identify patients with a very high probability of disease: these patients most likely have the disease and therefore the test will be unnecessary.
Calculation of pre-test probability (PTP)
The likelihood of coronary artery disease is a function of disease prevalence and patient characteristics.
If the patient represents a population with a high prevalence of coronary heart disease and exhibits all symptoms of the disease, then PTP is very high. In that scenario, the usefulness of diagnostic tests decreases because they will almost certainly only confirm an already probable diagnosis. The opposite is also true; if the disease is rare and the patient presents no symptoms consistent with the disease, then an examination is unlikely to reveal anything useful. In general, diagnostic tests are most useful when used in patients with an intermediary likelihood of disease.
If the probability of coronary heart disease is low and the examination is negative, then coronary heart disease can be excluded.
If the probability of coronary heart disease is high and the examination is positive, then coronary heart disease can be confirmed.
The pre-test probability of coronary heart disease is estimated based on sex, age, and symptoms (Figure 1).
Figure 1. Pre-test probability of coronary artery disease (angina pectoris) as a function of age, sex, and symptoms.
If PTP is <5% then coronary artery disease is unlikely. This should imply that other diagnoses are more likely, and additional investigations for coronary artery disease should only be done in special circumstances. The usefulness of non-invasive tests is greatest if PTP is >15%. If PTP is 5 to 15%, the following parameters should be taken into account for assessing the clinical likelihood of coronary heart disease:
Risk factors
Medical history and status
ECG findings
Echocardiographic findings.
The clinical probability of coronary artery disease increases with the number of factors that are consistent with coronary artery disease. Thus, the clinical probability of coronary heart disease is the sum of PTP and the above parameters (risk factors, history, status, resting ECG, echocardiography).
Coronary calcium score can be considered when assessing clinical probability. Note, however, that some atherosclerotic plaques have a low calcium concentration, despite high-grade stenosis, which is why calcium score can not be used to exclude coronary heart disease.
Sensitivity and specificity of exercise stress test
Sensitivity and specificity are often used to describe the accuracy of a given diagnostic method. These measures may be defined as follows:
| Sensitivity | The proportion of those with the disease who are detected. |
|---|---|
| Specificity | The proportion of those who are healthy who are correctly classified as such. |
The sensitivity and specificity of exercise stress testing depend on several variables, such as the prevalence of the disease in the population, the criteria used, and so on. The sum of all evidence indicates that sensitivity is around 60–75% and specificity is 60–85% for exercise stress testing. However, sensitivity is lower in people with one-vessel disease (<50% sensitivity) and higher in those with three-vessel or left main stem disease (>85%).
References
Jonathan H Kim, Rajeev Malhotra, George Chiampas, Pierre d’Hemecourt, Chris Troyanos, John Cianca, Rex N Smith, Thomas J Wang, William O Roberts, Paul D Thompson, Aaron L Baggish. Cardiac arrest during long-distance running races. Race Associated Cardiac Arrest Event Registry (RACER) Study Group. N Engl J Med . 2012 Jan 12;366(2):130-40.
Chapter 2: Indications, Contraindications, and Preparations for Exercise Stress Testing
In this article, we will discuss indications, contraindications, and subject preparations. We will also discuss the relevance of withholding specific cardioactive medications during exercise testing (exercise ECG).
Indications for exercise stress test
Indications have been discussed in Introduction to Exercise ECG. The most common indications are as follows:
Assessment of cardiovascular risk in screening.
Detection of coronary artery disease (ischemic heart disease).
Evaluation of coronary artery disease.
Assessment of therapeutic response. Exercise testing can be used to evaluate the effect of medications or interventions such as PCI, CABG, CRT, etc.
Assessment of perioperative risk for noncardiac surgery.
Exercise prescription.
Determine the degree of disability.
Contraindications for exercise stress test
Although exercise stress testing is a safe procedure, the risk of complications calls for careful consideration of contraindications. Contraindications may be absolute or relative. Briefly, exercise stress testing must not be performed in the presence of absolute contraindications. Relative contraindications call for an individualized assessment of the risks; if the benefit outweighs the risk, then relative contraindications may be disregarded.
Absolute contraindications for exercise ECG
Aortic dissection – due to risk of progression and rupture.
Acute myocardial infarction (AMI) within 48 hours – due to the risk of aggravating the infarction, as well as inducing ventricular arrhythmias.
Unstable angina pectoris in the acute phase (before stabilization of symptoms) – due to the risk of developing acute myocardial infarction and inducing ventricular arrhythmias.
Presence of potentially serious arrhythmias – due to the risk of circulatory collapse.
Decompensated heart failure – due to the risk of circulatory collapse and arrhythmias
Pulmonary embolism in acute phase – due to risk of aggravation of the condition.
Pulmonary infarction in acute phase – due to risk of aggravating the condition.
Perimyocarditis (myocarditis) in acute phase – due to risk of arrhythmias
Severe aortic stenosis – due to risk of syncope, ischemia, and arrhythmias
Endocarditis – due to risk of embolization
Deep venous thrombosis – due to risk of embolization
Relative contraindications for exercise ECG
Severe hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg).
Left main coronary artery stenosis
Severe electrolyte imbalance
Severe hyperthyroidism
Moderate to severe aortic stenosis
Insufficiently controlled arrhythmias which may cause hemodynamic compromise
Obstructive hypertrophic cardiomyopathy
Second-degree AV block or third-degree AV block (not caused by medications)
Stroke within 1 month
Preparations for exercise stress testing
The laboratory and personnel
Exercise stress testing may be conducted by physicians, nurses, biomedical analysts, or other professionals. A physician is always formally responsible for conducting the test. All personnel must be appropriately trained and the laboratory must be equipped with defibrillators and other emergency instruments. Personnel conducting the test must be formally trained to assess cardiovascular response, symptoms, and ECG changes. Although the risk of cardiac arrest is very small, personnel must be well-trained in resuscitation.
Subject preparations
The procedure must be explained carefully to the patient, who must also be informed that his/her performance will affect the validity of the test. Hence, the patient must understand how the test is conducted in order to maximize its usefulness. The patient must be able to communicate, and an interpreter may be necessary if there is a significant lingual barrier.
Two hours of fasting before the test is recommended. Shoes and clothing should be suitable for exercise. Motivation is of utmost importance because the patient must perform a maximal workload. The meaningfulness of the test depends on the achievement of a high workload, preferably the patient’s peak exercise capacity.
The most recently recorded 12-lead (resting) ECG should be at hand before the start of exercise. Another resting 12-lead ECG is recorded just before the start of exercise. These two recordings are compared in order to determine whether the patient has developed arrhythmias or morphological changes (particularly myocardial infarction, which is typically assessed using criteria for pathological Q-waves).
The 12-lead resting ECG recorded before exercise is recorded using Mason-Likar’s limb lead placement (Figure 1, below), which implies that the limb leads are placed on the torso, instead of distally on the limbs (ECG limb lead placement has been discussed). Removal of chest hair will improve the quality of the recording.
Figure 1. Lead placement for exercise ECG. Note that the placement of precordial (chest) leads is not changed. The limb leads are relocated to the torso. This reduces artifacts (muscle artifacts) during exercise stress testing.
Physical examination and anamnesis must be obtained before the start of exercise. Cardiopulmonary auscultation is mandatory. Symptoms, medications, medical history, allergies and contraindications must be scrutinized carefully. Blood pressure is measured at rest before the start of exercise.
Cardioactive medications
Beta-blockers, calcium channel blockers, nitrates
In some circumstances, it is necessary to withhold cardioactive medications during the exercise test. Beta-blockers have a negative inotropic effect (i.e. reduces contractility) and a negative chronotropic effect (i.e. reduces heart rate). These two effects will reduce myocardial oxygen consumption and thereby alleviate myocardial ischemia, which will reduce both ischemic symptoms and ECG changes. Hence, beta-blockers have anti-ischemic effects which may mask myocardial ischemia and thus cause a false-negative test result. Beta blockers should therefore be withheld 24 hours before the test. The same is true for calcium channel blockers and nitrates, due to their anti-ischemic effect. Withholding these drugs for one day does not confer any significant risk to the patient.
Note that beta-blockers should not be withheld in patients conducting the test in order to assess functional capacity and cardiovascular response. The purpose of the test in that scenario is to assess capacity during optimal circumstances.
Digitalis (digoxin)
Digitalis (digoxin) may cause generalized ST segment depressions in all individuals. Such ST depressions may be accentuated during exercise. Digitalis should be withheld 24 hours before exercise testing. Cardiac imaging can be recommended to improve the specificity in patients taking digitalis. Note that exercise-induced ST depressions may persist for two weeks in some patients after discontinuation of digitalis.
Chapter 3: Exercise stress test (exercise ECG): protocols, evaluation & termination
Exercise stress test (exercise ECG) protocols & equipment: cycle ergometer (bicycle) vs. treadmill
The choice of exercise equipment and protocol depends mainly on local traditions. The treadmill and cycle ergometer (bicycle) are the most frequently used test methods. Cycle ergometer is preferred in Europe, while treadmill testing is predominant in the United States. Treadmill and cycle ergometer both have their advantages and disadvantages, which will be discussed below. The basic principles of exercise test protocols will also be discussed in this article.
Metabolic equivalent (MET): measuring oxygen consumption
Estimation of oxygen consumption is central to the assessment of exercise capacity. Metabolic equivalents (METs) can be used to estimate the energy cost of physical activity. One metabolic equivalent (1 MET) is defined as the amount of oxygen consumed while sitting at rest and is equal to 3.5 ml O2 per kg weight × min. Metabolic equivalents are used because the concept offers an easy way of expressing the energy cost of any exercise. The energy cost is expressed as multiples of the resting metabolic rate. For example, 5 METs imply that the energy cost of activity is equal to five times the energy consumption at rest (sitting). METs may be used to describe the functional capacity during exercise stress testing. Results of treadmill tests are typically described in METs, whereas energy expenditure during bicycle ergometry is typically expressed in kilopond meters per minute. Note that kilopond meters per minute can be converted to Watts (1 kilopond meter per minute = 0.1634 Watts).
Protocols for clinical exercise testing generally include an initial warm-up period (at a low workload), followed by a successive (graded) increase in workload. The increase in workload occurs with predefined time intervals. A recovery period, during which the patient is still carefully observed, follows after the exercise effort is terminated.
Reliability as a function of workload
In order for the exercise test to be reliable, the patient must perform maximally, without risking serious complications. The instructor may facilitate this by supporting and motivating the patient during the entire procedure. If the achieved workload is not sufficient, the reliability and thus usefulness of the test will be inadequate. The whole purpose of the exercise ECG is to provoke physiological reactions that are not noticeable at rest. Hence, the examination may only be considered conclusive if the achieved workload is sufficient to provoke symptoms/signs that are not noticeable during rest. As a rule of thumb, the patient must achieve 85% of the (age-adjusted) expected maximum heart rate, which can be estimated using the following formula:
Expected maximum heart rate according to age and sex.
Accordingly, a 65-year-old male is estimated to have a maximum heart rate of 208-65×0.7, which equals approximately 163 beats per minute; and 85% of 163 is roughly 140. That male should therefore achieve a heart rate of 140 beats per minute for the exercise test to be reliable.
It should be noted that 85% is an arbitrary number and the exercise test must never be terminated once the patient has reached 85% of the expected maximum heart rate. The reasons for this follows:
There is substantial individual variation in maximum heart rate. The standard deviation for maximum heart rate is around 10 beats per minute, which means that if the expected maximum heart rate is 160 min according to the equations above, it may actually be anywhere between 140 and 180 beats per minute.
Patients with significant heart disease (known or unknown) may not achieve the expected maximum heart rate and it may be hazardous to push them towards it.
It is therefore recommended that the 85% cut-off be used only as a guiding principle rather than an absolute rule.
Evaluation of the exercise stress test: Parameters to assess
Evaluation of the exercise stress test is based on several parameters which must be assessed continuously during the procedure. These parameters are listed in the table below and discussed in detail in subsequent chapters.
| PARAMETER | COMMENT |
|---|---|
| General appearance | The presence of chest discomfort (pain) must be assessed repeatedly during the test. The severity of chest pain is graded from 0 (no pain) to 10 (maximal pain). |
| Chest discomfort (pain) | Maximal workload achieved and duration of the test |
| Dyspnoea/dyspnea and exercise effort | Leg fatigue is graded from 0 (none) to 10 (maximal. |
| Leg fatigue | Leg fatigue graded from 0 (none) to 10 (maximal. |
| Maximal workload acheived and duration of the test | Workload is expressed in METs, Watts, kpm, depending on protocol and test method. |
| Heart rate | Maximal heart rate is noted during the entire procedure (including the recovery period). Heart rate acceleration is also noted. |
| EKG/ECG reaction | Systolic blood pressure is measured every other minute. It is also measured at the termination of exercise and then every other minute during the recovery period. Automatic blood pressure monitor should not be used; measurements should be manual. |
| Blood pressure reaction | Systolic blood pressure is measured every other minute. It is also measured at the termination of exercise and then every other minute during the recovery period. An automatic blood pressure monitor should not be used; measurements should be manual. |
| Cause of termination | If the exercise test is terminated prematurely, the cause must be noted. |
Evaluation of ECG / EKG reaction
A 12-lead ECG is recorded at rest before the exercise test begins. That initial ECG is used as a baseline ECG and all subsequent ECGs (recorded during exercise) will be compared to it. In order to reduce artifacts from muscles and movements the ECG machine presents a signal-averaged ECG, which means that several consecutive ECG curves (waveforms) are averaged, which yields a clearer ECG curve. These signal-averaged ECG curves are continuously updated so that the clinician can monitor ECG changes in real-time. Note that the ECG machines detect ventricular extrasystoles (premature ventricular beats) and exclude them from the signal-averaged ECG. A separate rhythm strip is always available so that the clinician can monitor the frequency of ventricular extrasystoles.
ECG changes and their implications will be discussed in detail in subsequent articles.
The recovery period after termination of exercise
The recovery period starts immediately once the patient stops cycling/running. The patient is placed in the supine position which increases the venous return to the heart. The increased venous return will subsequently increase cardiac preload (a greater blood volume is returned to the left ventricle). Increased preload causes increased workload on the myocardium of the left ventricle and that may provoke myocardial ischemia due to increased oxygen consumption in the myocardium. Some patients only display ischemic ECG changes during the recovery period. Note that ECG recording continues during the entire recovery period, which is usually 6 to 8 minutes. The exercise test is terminated once all parameters (listed above) have returned to baseline values.
Termination of exercise
The exercise test is terminated when (1) symptoms are limiting the patient from continuing; (2) when formal termination criteria are fulfilled (defined below) or (3) when the test is completed.
Termination criteria
A plethora of studies conducted in the past few decades show that exercise stress testing is a safe procedure. The risk of complications is low, despite the fact that many participants have significant heart disease, including ischemic heart disease. However, one must always conduct tests with caution and terminate the test if the risk of complications is elevated. Hence, there are absolute and relative criteria for terminating a stress test.
Absolute termination criteria
The exercise test should be terminated in each of the following scenarios:
≥10 mmHg drop in systolic blood pressure in the presence of other signs suggestive of myocardial ischemia.
Systolic blood pressure >280 mmHg. This limit is lower if the patient has an increased risk of bleeding (e.g. patients on anticoagulants).
Pronounced angina pectoris (grade 5 or higher according to the visual analogous scale).
Dizziness, pre-syncope, or more severe neurological signs.
Cyanosis, paleness.
Patient’s desire to terminate.
Technical problems make ECG recording or blood pressure recording unreliable.
Ventricular tachycardia (VT) with duration >30 seconds.
Supraventricular tachyarrhythmia (tachycardia) with negative hemodynamic effects.
ST segment elevation 1 mm or higher in leads without (pre-existing) significant Q-waves.
ST segment depression >2 mm in two or more contiguous leads.
Relative termination criteria
In each of the scenarios listed below, one should consider terminating the test:
≥10 mmHg drop in systolic blood pressure (without other signs of myocardial ischemia).
115 mmHg diastolic blood pressure.
Marked change in the electrical axis (ECG).
AV (atrioventricular) block II, AV block III.
Multifocal premature ventricular beats (extrasystoles).
Frequent coupled premature ventricular beats.
Bradyarrhythmia (bradycardia).
Exhaustion.
Leg cramp
Chapter 4: Exercise stress testing in special patient populations
Clinicians should be familiar with the special challenges posed by some patient populations. The sensitivity, specificity, risks, and results of the exercise test may be affected by patient characteristics. For example, exercising patients with ongoing myocardial ischemia may provoke life-threatening ventricular arrhythmias.
Patients with previous acute coronary syndromes (ACS)
Exercise stress testing is routinely performed after acute myocardial infarction in order to assess the presence of myocardial ischemia, evaluate angina pectoris, evaluate exercise performance, evaluate the effect of interventions and medications, and prognosticate survival. However, exercise stress testing must not be performed within 4 to 6 days after acute myocardial infarction. Moreover, early exercise tests should not be maximal, which means that the clinician must set a lower goal regarding workload (e.g. reaching 70% of maximal pulse instead of 85%). Many patients appreciate the exercise test because it offers them an opportunity to evaluate their performance and symptoms under the supervision of their clinician. Indeed, kinesiophobia (fear of exercising) is common after myocardial infarction and it is associated with poorer survival.
Patients with unstable angina pectoris with low risk (according to TIMI score or similar) may undergo stress testing when their clinical condition is stabilized. This usually takes 2 to 3 days and the patient must not have experienced chest pain during the last 12 hours before exercise. Patients with unstable angina pectoris with high risk should not undergo exercise stress tests; these patients should be referred to angiography instead.
Exercise stress testing in women
Exercise ECG has lower sensitivity and specificity in women. This may be due to the following:
Atherosclerosis is generally less severe in women.
Women tend to have more difficulties reaching their maximal heart rate.
Exercise stress testing in the elderly
The Elderly also have difficulties reaching 85% of their maximal heart rate which hampers the utility of the stress test. However, the elderly also tend to have more atherosclerosis (both in frequency and severity) which may compensate for the inability to reach their maximal heart rate. Ultimately, the specificity of exercise stress testing is lower in the elderly, as compared to younger individuals. Sensitivity, on the other hand, appears to be similar.
Exercise stress testing and revascularization (PCI, CABG)
Stress testing is commonly performed at various stages before and after revascularization procedures (PCI or coronary artery bypass grafting [CABG]). Stress testing is used to establish the diagnosis of ischemic heart disease as well as estimating the extent of ischemia. After revascularization procedures, stress testing is utilized to assess whether there is any residual ischemia or angina pectoris. Patients may undergo repeated stress tests to assess symptoms and signs of ischemia.
(none)
Chapter 5: Exercise physiology: from normal response to myocardial ischemia & chest pain
Understanding the basic principles of exercise physiology is essential to conduct and evaluate the exercise stress test. Exercise induces physiological changes such as increased ventilation, coronary vasodilation, increase in blood pressure, etc. The purpose of such changes is simply to enable the cardiopulmonary system to increase its delivery of oxygen to skeletal muscle and myocardium. The oxygen consumption – and thus oxygen demand – increases in parallel with the intensity of the exercise. The physiological changes (adaptations) become more pronounced as the intensity of exercise increases. The autonomic nervous system is the first system to react to exercise. It does so by withdrawing parasympathetic activity and increasing sympathetic activity. This has multiple effects which are discussed in detail below. This article will deal with the physiology of exercise and emphasis will be placed on myocardial oxygen consumption and the development of myocardial ischemia during exercise. ECG changes are mentioned briefly (an in-depth discussion on ECG changes is provided in the next article).
Physiological effects of exercise
The main physiological effects of exercise are summarized below.
Parasympathetic fibers innervate both the sinoatrial (SA) node and atrioventricular (AV) node. Parasympathetic stimulation reduces the automaticity in the sinoatrial node, which lowers the heart rate. The parasympathetic activity also diminishes impulse transmission in the AV node. Thus, withdrawal of parasympathetic activity results in increased heart rate and increased impulse transmission across the AV node.
Sympathetic fibers innervate the entire heart, particularly the ventricular myocardium. Sympathetic stimulation has a positive inotropic effect (i.e increases contractile force in the myocardium), positive chronotropic effect (i.e increases the heart rate by increasing the automaticity in the sinoatrial node), and positive bathmotropic effect (i.e increased impulse transmission through the myocardium). Thus, increased sympathetic activity results in increased heart rate and stronger contractions.
Physical exercise increases the venous return to the heart, which results in increased cardiac preload. The mechanisms are as follows:
Sympathetic activity causes constriction of the veins, which increases the venous return to the heart.
Contracting muscles function as a pump that propels blood back to the heart.
The respiratory depth (volume) increases and this reduces the intrathoracic pressure by increasing the intrathoracic volume. Reduced intrathoracic pressure will passively suck blood back to the heart.
The increase in preload will lead to increased ventricular pressure and volume, which will, in turn, increase the stroke volume. This is explained by the Frank-Starling mechanism, which implies that the ventricular myocardium responds to increased ventricular pressure/volume by increasing its contractility. The Frank-Starling mechanism is amplified by the positive inotropic effects of the sympathetic stimulation. Increased stroke volume and increased heart rate lead to increased cardiac output.
Systolic blood pressure increases when cardiac output increases. Diastolic blood pressure is not affected by changes in cardiac output. Hence, diastolic blood pressure is not affected by exercise (occasionally it may even drop up to 10 mmHg). Mean arterial pressure (MAP) increases due to the fact that systolic blood pressure increases during exercise.
The increase in cardiac output during moderate exercise is the result of increased stroke volume and increased heart rate. However, when roughly half of the maximal cardiac output is achieved, the stroke volume cannot increase further, which means that a further increase in cardiac output depends on an increase in heart rate. As illustrated in Figure 1, cardiac output can increase 6 times during maximal exercise intensity.
Figure 1. The relationship between heart rate, stroke volume and cardiac output during exercise.
Withdrawal of parasympathetic activity and increased parasympathetic activity cause vasoconstriction in the renal arteries, abdominal arteries and skin. Thereby, the blood volume is redirected to muscles, heart and brain, where arteries are instead dilated to allow for increased blood flow. Vasodilation in muscles, heart and brain is caused by catecholamines, nitric oxide (NO) and accumulation of metabolic waste products. Vasoconstriction in the kidneys, skin and abdomen is roughly equal to vasodilatation in the brain, heart and muscles. Ultimately, the peripheral vascular resistance is barely affected by exercise.
Heart rate during exercise stress testing
Heart rate must increase once exercise starts. Heart rate should then increase almost linearly with workload. Well-trained individuals, as well as persons using beta-blockers, exhibit a slower increase in heart rate. Maximal heart rate is lower in the elderly due to diminished sensitivity to catecholamines. Heart rate drops rapidly during the first minute of recovery (due to the return of vagal activity) and thereafter the heart rate drops slowly until it is normalized (return to baseline).
Blood pressure response during exercise stress testing
Systolic blood pressure should increase steadily during exercise. Virtually all patients display systolic blood pressure above 150 mmHg. Diastolic blood pressure is either unchanged or may drop slightly (up to 10 mmHg). Men and elderly individuals display a more pronounced increase in systolic blood pressure. Once the exercise stops, blood pressure drops steadily until it is normalized, which usually takes 5 minutes. Note that systolic blood pressure may actually drop below baseline levels after exercise and it may take up to 6 hours before it returns to baseline values.
Myocardial metabolism and ischemia (ischemia)
Understanding the principles of myocardial metabolism is crucial in order to understand how various situations may provoke myocardial ischemia and infarction. Myocardial ischemia occurs when myocardial oxygen demand exceeds the oxygen supply. In other words, ischemia is the result of an imbalance between oxygen demand and oxygen supply. This imbalance may be due to acute artery occlusion (i.e acute coronary syndrome), chronic but stable coronary artery stenosis (i.e. atherosclerosis) or other non-coronary causes such as anemia. The main determinants of myocardial oxygen consumption are the following:
Blood pressure
Heart rate
Contractile force (contractility)
Ventricular wall tension
Oxygen demand is positively correlated with each of these. In other words, if blood pressure, heart rate, contractility or wall tension increases, then myocardial oxygen demand will also increase. The term ventricular wall tension simply refers to the workload on the ventricular wall; it is determined by the pressure in the ventricle, myocardial thickness and diameter of the ventricle.
It is obvious that measuring contractility and wall tension is too laborious for routine clinical practice. Blood pressure and heart rate are much easier to assess and the product of these two parameters (heart rate × blood pressure) actually provides a reasonable estimate of the myocardial oxygen demand. The product is often referred to as the rate-pressure product (or double product, or cardiovascular product):
Rate Pressure Product = Heart Rate (bpm) × Systolic Blood Pressure (mmHg)
Thus, the rate pressure product is an estimate of the stress put on the myocardium. It is based on the number of contractions per minute (heart rate) and the pressure that the ventricle is pumping against (systolic blood pressure). The rate pressure product offers a simple way to estimate oxygen demand and thus energy consumption of the heart. The aim during exercise stress testing is to achieve a rate pressure product of at least 25000, which indicates that the workload has been sufficient.
| Hemodynamic response (workload) | Rate pressure product |
|---|---|
| High | >30000 |
| High intermediate | 25000 – 30000 |
| Intermediate | 20000 – 25000 |
| Low intermediate | 15000 – 20000 |
| Low | 10000 – 15000 |
Under normal circumstances, the coronary blood flow adapts to myocardial oxygen demand. Coronary blood flow increases during exercise in order to meet the increased oxygen demands in the myocardium. Myocardial ischemia occurs if there are atherosclerotic plaques that cause stenosis of the artery. Atherosclerotic plaques vary in size; they may range from negligible to completely obliterating. A small stenosis rarely causes symptoms at rest, but it may cause symptoms during exercise because oxygen demand increases during exercise (the stenosis prevents the needed increase in oxygen delivery). The rate pressure product may be used to estimate the severity of a stenosis; symptoms of ischemia (angina pectoris) at low rate pressure products indicate that the stenosis is severe. Moreover, in a stable stenosis, ischemic symptoms typically arise at the same rate-pressure product. The rate pressure product is, however, only an approximation of myocardial workload and some studies actually show that the patient’s subjective rating of her performance is at least as good an estimate of myocardial workload.
Myocardial ischemia: lack of blood flow vs. supply/demand imbalance
Ever since Eugene Braunwald and colleagues elucidated the determinants of myocardial oxygen demand, researchers have debated the true nature of myocardial ischemia. There are two competing theories (the first one has already been presented above) which are briefly explained:
Most researchers have agreed on the supply and demand theory, which states that ischemia arises whenever demand exceeds supply. In other words, ischemia is the result of an imbalance between supply and demand.
The competing theory states that the myocardium can never experience imbalance because it adapts its oxygen consumption (metabolism) to the oxygen supply. In other words, the myocardium will reduce its oxygen consumption – and thereby contractility – if sufficient oxygen is not available. Accordingly, myocardial cell metabolism follows the oxygen supply. Metabolism is downregulated gradually as the oxygen supply diminishes; the more pronounced the lack of oxygen, the greater the reduction in metabolism (and thus contractility). This theory is supported by both research and clinical observations. For example, animal studies and clinical studies show that whenever coronary blood flow is cut off, the affected myocardium immediately stops contracting and becomes “stunned”. As blood flow returns, the myocardium gradually resumes its contractions. According to this theory, myocardial ischemia can only be the result of an absolute lack of oxygen.
Interested readers are referred to:• G Heusch, Myocardial Ischemia. Circ Res, 2016• E Braunwald, Limitation of Infarct Size and the Open Artery Theory. Circulation, 2016.
Nevertheless, it is clear that the degree of stenosis correlates well with the level of ischemia. A stenosis causing <50% luminal obstruction may not cause any symptoms at all. A stenosis causing 50–70% luminal obstruction typically causes symptoms (angina pectoris) during exercise. A stenosis causing 90% luminal obstruction generally causes symptoms at rest. Note that these principles are modified by several factors, of which the most important are:
Collateral circulation: Collateral arteries may be very effective. In fact, a complete occlusion of the left anterior descending artery (LAD) may not cause any symptoms if there are collateral vessels supplying the LAD.
Location of the stenosis: A proximal occlusion/stenosis will affect a larger portion of the myocardium, as compared to a more distal occlusion/stenosis.
Coronary autoregulation: Atherosclerotic coronary arteries tend to compensate for the stenosis by relaxing smooth muscle around the atherosclerotic plaque. This results in local vasodilation at the site of the plaque. Hence, in the early stages of atherosclerosis, the lumen (diameter) may not be affected by the plaque (which is why coronary angiography may also be false negative). However, as the atherosclerotic process continues and the plaque grows, it will gradually cause a narrowing of the lumen despite any autoregulatory mechanisms.
The length of the stenosis: A long stenosis will have a greater impact than a short stenosis.
The ischemic cascade: from ischemia to ECG changes and chest pain
Patients with acute coronary syndromes who are monitored with continuous ST segment monitoring only report symptoms in approximately 40% of the ischemic episodes detected with continuous ST segment monitoring. It follows that 60% of ischemic episodes are asymptomatic, which in turn implies that ischemic heart disease cannot be ruled out by the absence of symptoms. On the other hand, patients with symptomatic ischemic heart disease (i.e. angina pectoris) will almost invariably display ischemic ECG changes during episodes with chest pain. In summary:
60% of all ischemic episodes are asymptomatic.
Patients with chest pain due to myocardial ischemia will virtually always display ischemic ECG changes.
The ischemic cascade – which is the sequence of events that take place during an episode of ischemia – explains these matters. Figure 2 (below) illustrates the ischemic cascade. Study this figure carefully, as it clarifies why the absence of ischemic ECG changes during chest pain virtually rules out myocardial ischemia as the cause.
Figure 2. The ischemic cascade illustrates the course from ischemia to ECG changes and clinical symptoms. As illustrated, clinical symptoms (e.g. chest pain) are the last events during an ischemic episode. It follows that myocardial ischemia may be present even in the absence of clinical symptoms. Moreover, the ECG detects more ischemic episodes than the patient reports.
The ischemic cascade is the sequence of events that occur between the beginning of cellular ischemia and clinical symptoms. During exercise in patients with significant coronary artery stenosis, the myocardium receives less oxygen than is needed to meet the metabolic demands. The lack of oxygen results in diminished ATP (adenosine triphosphate) production and increased production of lactic acid. Diminished production of ATP leads to downregulation of cellular metabolism and contractility. The cell may actually stop contracting completely if the ischemia is severe. The term stunned myocardium refers to myocardium standing still due to severe ischemia. Downregulation of metabolism and contractility is necessary for the cell to survive ischemia (the consequence of ischemia would be more severe if the cellular processes had continued unaltered during ischemia). The diminished availability of ATP affects the cell membrane proteins (particularly ion channels). This ultimately results in altered cell membrane function and changes in the electrical potentials across the cell membrane, which in turn causes ST segment depressions. Clinical symptoms (notably chest pain) arise if the ischemia is allowed to continue. This sequence of events is outlined in Figure 2 above. Note the following:
There is a limit for how long the cell can survive ischemia, even if it downregulates metabolism. In general, the myocardium survives severe ischemia for 20 minutes before the ischemic cells die.
The ischemia only causes ECG changes if it affects enough myocardium. ECG changes occur before clinical symptoms. In other words, clinical symptoms (e.g. chest pain) are the last events during an ischemic episode. It follows that myocardial ischemia may be present even in the absence of clinical symptoms. The ECG detects more ischemic episodes than the patient experiences.
Chapter 6: Evaluation of exercise stress test: ECG, symptoms, blood pressure, heart rate, performance
The ECG reaction has always been a central component of the exercise stress test. Indeed, clinicians often use the term exercise ECG instead of the correct term exercise stress test. However, the ECG is only one of the parameters that must be evaluated and the final result of the test depends on an integrated assessment of six components:
Symptoms
Exercise performance (functional capacity, exercise capacity)
Heart rate: maximal heart rate, heart rate response
Blood pressure reaction
ECG reaction: ST changes, T-wave changes, arrhythmias, conduction defects
Cause of termination
This article will discuss each of these six parameters in detail.
Symptom during exercise stress testing
Perceived exertion
The patient’s perceived exertion is a way of estimating the intensity of the physical activity. It is based on the subjective physical sensations experienced during exercise, including increased heart rate, increased respiratory rate and depth, increased sweating, and muscle fatigue. Although this is a subjective measure, it provides a fairly good estimate of the actual workload. The perceived exertion may be graded from 0 (none) to 10 (maximal exertion) or according to the Borg scale. The Borg scale is well validated at ranges from 6 (none) to 20 (maximal exertion). Notably, a high perceived exertion at a low workload is a strong predictor of adverse outcomes.
Table 1. Borg Rating of Perceived Exertion Scale
| RATING | LEVEL OF EXERTION | COMMENT |
|---|---|---|
| 6 | No exertion at all | |
| 7 | ||
| 7.5 | Extremely light exertion | |
| 8 | ||
| 9 | Very light exertion | For a healthy person, 9 is equivalent to walking slowly at his or her own pace for some minutes. |
| 10 | ||
| 11 | Light exertion | |
| 12 | ||
| 13 | Somewhat hard exertion | “Somewhat hard” exercise, but it still feels OK to continue. |
| 14 | ||
| 15 | Hard (heavy) exertion | |
| 16 | ||
| 17 | Very hard exertion | A healthy person can still go on, but he or she really has to push him- or herself. It feels very heavy, and the person is very tired. |
| 18 | ||
| 19 | Extremely hard exertion | For most people this is the most strenuous exercise they have ever experienced. |
| 20 | For most people, this is the most strenuous exercise they have ever experienced. |
There is a strong correlation between a person’s perceived exertion rating times 10 and the actual heart rate during exercise; so a person’s exertion rating provides an estimate of the actual heart rate. For example, if the perceived exertion is 12, then 12 x 10 = 120; so the heart rate should be about 120 beats per minute.
Chest pain (chest discomfort)
Chest pain during exercise is one of the strongest predictors of coronary artery disease. The severity of the pain may be graded from 0 (none) to 10 (maximal pain). It is important to clarify whether the pain provoked by exercise is similar to the pain that leads to the stress test (if that was the reason for conducting the test). Chest pain rated as 6 or above (according to the 10-point scale) should prompt termination of the stress test (refer to Termination criteria during stress testing).
Dyspnea (dyspnoea)
Exercise does lead to tachypnea (increased respiratory rate), which should, however, be distinguished from dyspnea which is shortness of breath. Dyspnea may be due to poor exercise capacity (with normal ventilatory capacity and cardiac output), diminished ventilatory capacity, diminished cardiac output or an angina equivalent. Note that women, diabetics and older individuals with coronary artery disease may only present with dyspnea (which is then considered an angina equivalent). Notably, terminating the test due to dyspnea is associated with a worse prognosis than termination due to chest pain.
Leg fatigue
Leg fatigue is particularly pronounced on bicycle, and less pronounced on the treadmill. Leg fatigue is, as compared with chest pain and dyspnea, a poor predictor of cardiovascular and all-cause mortality. However, leg fatigue must be registered.
- Exercise performance (functional capacity, exercise capacity)
Exercise performance is probably the single best predictor of risk for future adverse events in healthy individuals, those at increased risk for cardiovascular disease, and actually all patient populations. This is true independent of other traditional risk factors. The correlation between exercise capacity and survival is almost linear, meaning that survival increases along with increased exercise capacity.
Performance is estimated using the maximal heart rate, rate pressure product, duration of the test, and the patient’s perceived exertion rating. The combined results of these parameters indicate the patient’s exercise capacity. For example, if the patient reaches the age-expected maximal heart rate, a high rate-pressure product, and endures the entire test without rating it as extremely hard, he or she has an excellent exercise performance. The inability to reach 85% of the age-expected maximal heart rate is associated with an increased risk of cardiovascular and overall mortality. Coronary artery disease, sinus node dysfunction (chronotropic incompetence), heart failure, left ventricular dysfunction, poor physical fitness, pulmonary disease etc are common causes. Note that some patients may perform well below their actual capacity without any medical explanation; it is important to motivate the patient before and throughout the test so that he or she performs maximally.
- Heart rate response during exercise stress testing
Please refer to the previous paragraph.
- Blood pressure response during exercise stress testing
Systolic blood pressure must exceed 140 mmHg during the test. Systolic blood pressure >200 mmHg may indicate an abnormal blood pressure reaction, which is typically seen in patients with hypertension as well as normotensive patients who will eventually develop hypertension.
A fall in blood pressure during the test indicates coronary artery disease or cardiomyopathy. The blood pressure may drop gradually as the workload is increased, or it may drop after an initial (normal) increase in blood pressure. Both scenarios are pathological. The test should be terminated if blood pressure drops 10 mmHg or more and there are other signs of ischemia. Termination of the test should always be considered when blood pressure drops 10 mmHg or more.
- ECG reaction
ST segment depressions during exercise stress test
The myocardial ischemia that can be provoked by exercise is located in the subendocardium of the left ventricle. As discussed previously (refer to ST segment depression in ischemia), subendocardial ischemia redirects the ST vector such that it becomes directed from the epicardium to the endocardium, which means that the ST vector will be directed towards the back (Figure 1). Hence, the ST vector is directed away from all chest leads (V1, V2, V3, V4, V5, V6). Chest leads that detect this ST vector will display ST segment depressions (because the ST vector heads away from these leads). However, leads with ST segment depressions do not necessarily reflect the ischemic area; e.g. ST segment depressions in leads V3 and V4 do not necessarily imply that the ischemia is located anteriorly.
The T-wave vector may similarly be directed towards the back which yields a negative T-wave (T-wave inversion). However, the primary ECG manifestation of myocardial ischemia (during exercise) is the ST segment depression and not the T-wave inversion. Myocardial ischemia does not manifest only with T-wave inversions during exercise; if there are T-wave inversions during ischemia, there will always be ST segment depressions as well. The ST segment, on the other hand, can be depressed (during ischemia) without simultaneous T-wave inversion. In summary:
ST segment depression is the hallmark of myocardial ischemia (during exercise) on the ECG.
ST segment depression may be isolated or accompanied by T-wave inversions (negative T-waves).
T-wave inversion (negative T-waves) never appears without simultaneous ST depression in patients with myocardial ischemia.
Figure 1 illustrates how subendocardial ischemia generates ST vectors that lead to ST depression and inverted T-waves.
Figure 1. Exercise causes subendocardial ischemia and thus ST segment depression on the ECG.
Measuring ST depression: J point, J 60 point & J 80 point
ST segment depression is measured anywhere between the J-60 point and J-80 point. The J-60 point and J-80 point are located 60 ms and 80 ms, respectively, after the J point (Figure 2). As usual, the PR segment is the reference (baseline) level. The magnitude of the ST depression is simply the difference (in millimeters) between the PR segment and the J-60/J-80 point.
Study Figure 2 (below) carefully, as it illustrates the J point, J 60 point, J 80 point, and the baseline to which these points are compared.
Figure 2. Measurement of ST segment depression during exercise stress testing.
Types of ST segment depressions
ST segment depressions may be characterized as (1) J point depressions, (2) upsloping ST depressions, (3) horizontal ST depressions, or (4) downsloping ST depressions. These types are illustrated in Figures 3 and 4. Myocardial ischemia causes ST segment depressions with horizontal or downsloping ST segments, which is illustrated in Figure 3. The depression should be 1 mm or more in the J-60 point or J-80 point (or anywhere between). 1 mm ST depression provides a sensitivity of 70% and specificity of 80% for coronary artery disease. The deeper the ST depression, the greater sensitivity and specificity.
Myocardial ischemia is diagnosed if there is ≥1 mm horizontal or downsloping ST depression in J-60/J-80 point (or between J-60 and J-80).
The typical ischemic ST depression is illustrated in Figure 3, below.
Figure 3. ST segment depressions that are typical of ongoing myocardial ischemia.
Non-ischemic ST segment depressions
Approximately 20% of healthy individuals exhibit upsloping ST depression during exercise stress testing. Upsloping ST depressions are thus very common during exercise and they are not typical of myocardial ischemia. If only the J point is depressed (Figure 4, left panel), then it is referred to as J point depression. J point depression is normal during exercise and it is not a diagnostic problem because there is no actual ST depression. In summary, J point depression is not caused by ischemia.
The right panel of Figure 4 shows an upsloping ST depression with a depressed J-60 point and J-80 point. Such ST depressions are also common during exercise and situations with tachycardia. These ST depressions do, however, cause differential diagnostic problems, because in a minority of cases they are caused by ischemia. The following characteristics suggest that upsloping ST depressions may be of ischemic origin:
If the ST depression is very pronounced (≥1.5 mm)
The smaller the inclination of the slope, the more likely is ischemia.
The steeper the slope the less likely is ischemia.
The more horizontal the slope the more likely is ischemia.
If the ST depression appears at low workload then ischemia should be considered.
Nevertheless, in the majority of cases, the upsloping ST depressions are not caused by ischemia. Non-ischemic ST depressions are illustrated in Figure 4, below.
Figure 4. ST segment depressions not typical of myocardial ischemia.
ECG leads to detect ischemia
ECG leads V4, V5 and V6 are the best leads to detect ischemia during exercise. These leads have the highest sensitivity for myocardial ischemia, which means that the probability of detecting ischemia is highest in these leads. The limb leads are less sensitive in terms of detecting ischemia. However, ST segment depressions in lead -aVR suggest severe myocardial ischemia (multivessel disease or left main disease).
If ST segment depressions occur early in the test, or if ST depressions are pronounced, or if ST depressions occur in many ECG leads, then there is probably extensive myocardial ischemia. The probability of multivessel disease increases with the number of leads showing ST segment depressions. Moreover, ST depressions with long duration during the recovery period also suggest more severe coronary artery disease.
Note that some patients only display ST depression during the recovery period. This is explained by the fact that myocardial workload increases once the patient is placed in the supine position (the preload of the heart increases because of increased venous return in a supine position).
Figure 5 (below) illustrates the ECG reaction of a male with coronary artery disease.
Figure 5. Exercise ECG in patient with coronary artery disease shows significant ST depressions in J-60 point, J-80 point. These depressions become more pronounced as workload increases. This test was performed on bicycle.
To distinguish normal (physiological) ST depressions from ischemic ST depressions, the following rules are suggested:
Normal (physiological) upsloping ST depressions only occur at high heart rates. Upsloping ST depressions due to ischemia occur already at low heart rates.
Normal (physiological) upsloping ST depressions are rapidly normalized during the recovery period. Upsloping ST depressions due to ischemia are slow to normalize during the recovery period.
Normal (physiological) upsloping ST depressions have a steeper slope than ischemic ST depressions.
Normal (physiological) upsloping ST depressions rarely exceed 1.5 mm.
Patients with ST depressions on resting ECG
In patients with ST segment depressions on resting ECG (e.g. due to left ventricular hypertrophy), the ST depression is measured from the initial level (at rest) of the J-60/J-80 point (and not from the level of the PR segment). Moreover, if there are ST depressions at rest, additional ST depression induced by exercise will not be as specific to ischemia as is otherwise the case (unless the depressions are very pronounced).
Atrial repolarization may mimic ST depression
Atrial repolarization occurs simultaneously with ventricular depolarization (QRS complex), which generates stronger electrical potentials and therefore conceals atrial repolarization. Occasionally during exercise, atrial repolarization may become visible and create a negative wave just after the QRS complex. This may imitate an ST segment depression, particularly in the inferior leads.
Complete results from an exercise test: clinical case
A 58-year-old male was admitted to the emergency room due to chest discomfort. He had experienced chest discomfort almost daily during the past few months. His resting 12-lead ECG was normal, as were laboratory tests, including troponin T. The exercise stress test revealed myocardial ischemia (results below). The patient underwent coronary artery bypass grafting (CABG) due to left main disease. Below are all the test results.
- Overview of test results
Figure 6. Overview of test results. 58-year-old male with left main disease.
- ECG reaction in the limb leads
Figure 7. ECG reaction in limb leads during exercise.
Figure 8. ECG reaction in limb leads during recovery.
- ECG reaction in chest (precordial) leads
Figure 9. ECG reaction in chest leads during exercise.
Figure 10. ECG reaction in chest leads during recovery.
Evaluating ST depression in relation to heart rate: frequency adjusted ST depressions
Some experts emphasize that heart rate must be taken into consideration when judging ST segment depressions. Taking heart rate into account may actually facilitate differentiating normal (physiological) ST segment depressions from ischemic ST segment depressions. The rationale for this is as follows:
Healthy individuals often achieve high heart rates which may induce normal (physiological) ST depressions (typically with an upsloping ST segment) that are not caused by ischemia. Approximately 20% of healthy subjects display ST depression during exercise testing.
Patients with coronary artery disease frequently fail to achieve sufficient workload (heart rate) to provoke myocardial ischemia. The ST depressions may not reach the criteria of 1 mm because of insufficient workload.
Thus, adjusting the magnitude of the ST depression to the heart rate may be a reasonable approach. ST depressions occurring at high heart rates are given less significance, while ST depressions occurring at low heart rates are given more significance. The adjustment can be made by either the ST/HR index or ST-HR slope.
The ST/HR index
The magnitude of the ST depression (in mV, where 0.1 mV = 1 mm) is divided by the heart rate increase during the test. An example follows:
Maximal ST depression during the test is 2 mm, which equals 0.2 mV.
The heart rate increased from 70/min (at rest) to 170/min (at maximal workload), which equals an increase of 100/min.
HR index = 0.2 / 100 = 0.002 mV/beat/minute
An HR index above 0.0016 mV/beat/minute suggests myocardial ischemia.
ST-HR slope
This parameter is calculated automatically in most ECG machines. It is the slope of the linear association between the heart rate and the amplitude of the ST depression. An ST-HR slope greater than 2.4 mV/beat/minute is significant.
ST segment elevation during exercise stress testing
ST segment elevation during exercise stress testing is measured in the J-60 point (whereas ST elevation is measured in the J-point on the resting ECG). In patients with ST elevations on the resting ECG (e.g. male pattern, early repolarization, left ventricular hypertrophy, etc), any additional ST elevation induced by exercise is measured from the initial level of the J-60 point (and not the level of the PR segment).
The implication of ST elevations during exercise depends on whether they occur in leads with or without pathological Q-waves.
ST elevation in leads without pathological Q-waves
ST elevations in leads without pathological Q-waves are rare during exercise stress testing. Such ST elevations indicate transmural ischemia, i.e. ischemia that affects the entire thickness (from endocardium to epicardium) of a myocardial region. This type of ischemia requires a (more or less) complete obstruction of blood flow, which may be explained by the following:
Acute coronary syndrome (rupture of an atherosclerotic plaque) emerges during the test. The thrombosis caused by plaque rupture may occlude the artery completely.
Presence of a severe and proximal stenosis (>90% luminal obstruction).
Coronary artery vasospasm.
Importantly, the stress test must be terminated if ST segment elevations occur in leads without pathological Q-waves.
ST elevations in leads with pathological Q-waves (previous myocardial infarction)
ST elevations may occur in leads with pathological (infarction) Q-waves. Such ST elevations may be caused by the following conditions:
Residual ischemia in the infarct area
Left ventricular aneurysm
Wall motion abnormalities
Reciprocal ST depression may be evident in each of these cases. If transmural ischemia cannot be ruled out, then the test must be terminated.
Psuedonormalization of ST-T changes
ST depressions and T-wave inversions that are present during rest but disappear during exercise indicate an abnormal reaction. If the patient has a high pre-test probability, this should lead to suspicion of myocardial ischemia.
Other morphological ECG changes
The PR interval and QRS duration are shortened during exercise (normal reaction).
Septal q-waves in leads I, aVL, V5, V6 may be accentuated during exercise (normal reaction).
The R-wave amplitude may decrease during exercise (normal reaction).
T-wave amplitude may decrease or increase (during heavy workload) during exercise, both of which are normal reactions.
QT duration is shortened by exercise (normal reaction).
If U-waves are evident on resting ECG and become inverted during exercise, it suggests myocardial ischemia.
Arrhythmias occurring during exercise stress testing
Supraventricular and ventricular arrhythmias may occur during exercise. This is more common in persons taking digoxin (digitalis) and those with coffee or alcohol in their blood. The subendocardial ischemia induced by exercise rarely induces any serious arrhythmias. In fact, exercise may actually suppress arrhythmias that are present at rest. For example, ectopic atrial arrhythmias may be suppressed when the sinoatrial node accelerates its discharge frequency; ventricular extrasystoles (premature beats) may also be suppressed during exercise. This has no prognostic implication.
Sinus arrhythmia and sinus bradycardia may occur during or after exercise. Atrial fibrillation and atrial flutter occur in 0.1% of all tests.
The only exercise-induced arrhythmia that is related to coronary artery disease is ventricular tachycardia (VT). Ventricular extrasystoles are common during exercise and they have no prognostic implication (ventricular extrasystoles are harmless unless there is electrical instability in the ventricles).
Conduction defects (disturbances) during exercise stress testing
Bundle branch block and fascicular block may occur during exercise. Left bundle branch block (LBBB) indicates underlying heart disease, particularly ischemic heart disease. Right bundle branch block (RBBB) may also occur, even in healthy individuals and it is not considered a sign of heart disease.
Atrioventricular (AV) block is uncommon during exercise, with the exception of first-degree AV block which is frequently seen during the recovery period (return of Vagal activity). Any degree of AV block during exercise and high-degree AV block (second-degree AV block or third-degree AV block) in the recovery period suggest ischemic heart disease.
The recovery period
Occasionally, ST segment depressions are only seen during the recovery period (the preload of the heart increases in the supine position). The duration of the recovery period is 6 to 8 minutes, during which the patient must be monitored. The test is completed when all parameters have returned to their baseline values.