Exercise Electrocardiographic Testing: Indications, Limitations and Interpretation

Definition and clinical role

Exercise electrocardiographic testing is a standardized assessment in which a patient performs progressively increasing external work, usually on a treadmill, while symptoms, a 12-lead ECG, heart rate and blood pressure are monitored. The test is generally symptom-limited and is stopped when limiting symptoms, significant electrocardiographic changes, arrhythmias or an abnormal haemodynamic response occurs, or when a predefined target heart rate is reached.

Its principal outputs are:

• Functional capacity and exercise tolerance

• Reproduction and characterization of symptoms

• Heart-rate and blood-pressure responses to exercise

• Detection of exercise-induced arrhythmias

• Identification of exercise-related ST-segment changes

• Prognostic and risk-stratification information

• Assessment of response to selected medical, revascularization, rehabilitation, ablative or surgical interventions

The test does not define the structure or composition of coronary atherosclerotic plaque, identify plaques at high risk of rupture, or determine whether ischaemia would occur at workloads greater than those achieved during testing.

Exercise ECG has become less prominent as a primary diagnostic test for obstructive coronary artery disease (CAD), because coronary computed tomography angiography (CCTA) and functional imaging have higher diagnostic performance. Its most consistent contemporary role is therefore the assessment of functional capacity, symptoms, haemodynamic responses, arrhythmias and prognosis, with diagnostic interpretation reserved for appropriately selected patients.

Pathophysiological basis

Exercise progressively increases myocardial oxygen demand through increases in heart rate, myocardial contractility and blood pressure. When coronary blood flow cannot increase adequately because of flow-limiting disease, myocardial ischaemia may develop. The electrical manifestation may be horizontal or downsloping ST-segment depression, reflecting an abnormal repolarization response to exercise-induced myocardial oxygen supply–demand imbalance.

The exercise response is not confined to the ECG. Ischaemia may also produce angina, impaired exercise capacity, an abnormal blood-pressure response or ventricular arrhythmias. A fall in systolic blood pressure, particularly when accompanied by evidence of ischaemia, may indicate exercise-induced global left-ventricular dysfunction.

Exercise testing also provides physiological information independent of ischaemia. Maximal exercise capacity, expressed by exercise duration, workload or metabolic equivalents, is among the strongest predictors of mortality in patients with cardiovascular disease after accounting for age. Chronotropic response, blood-pressure behaviour and the development of arrhythmias provide additional information concerning cardiovascular reserve and electrical stability.

Clinical indications

Suspected chronic coronary syndrome

Exercise ECG may be used in selected patients with suspected chronic coronary syndrome when the result is expected to influence diagnostic strategy or management. Appropriate objectives include:

• Measuring exercise tolerance

• Determining whether symptoms are reproduced by exertion

• Assessing the relationship between symptoms and ECG changes

• Detecting exercise-induced arrhythmias

• Evaluating the blood-pressure response

• Refining risk stratification and prognosis

For patients with low or moderate pre-test likelihood of obstructive CAD, CCTA or functional imaging should generally be preferred when available. Exercise ECG is not recommended as a rule-out test in this group if those modalities are accessible. It may nevertheless remain useful when imaging is unavailable, or in individuals with a low pre-test likelihood in whom a negative test may reduce the estimated likelihood sufficiently to defer further investigation.

In patients with established CAD, exercise ECG may complement clinical evaluation by documenting changes in symptoms, exercise tolerance, ST-segment response, arrhythmias, blood pressure and event risk.

Acute chest pain

Exercise ECG has historically been used for additional risk assessment after an initial evaluation of acute chest pain. Early testing may be safe in clinically low-risk patients without ongoing chest pain or other high-risk findings, provided serial ECGs and cardiac troponin assessment do not indicate myocardial ischaemia. However, when both troponin and clinical risk stratification indicate a low probability of acute coronary syndrome, available evidence does not establish that routine stress testing or cardiac imaging improves outcomes.

Exercise ECG remains an alternative for patients without known CAD who remain eligible for further assessment because of intermediate acute coronary syndrome risk. In patients with known coronary atherosclerosis, exercise testing should be performed with cardiac imaging.

Risk stratification and prognosis

Exercise ECG can be used to refine prognosis, particularly when the exercise capacity and clinical response are clearly characterized. Findings associated with higher risk include:

• Low exercise capacity

• Marked ischaemia at a low workload

• A high-risk Duke Treadmill Score

• Extensive or substantial ST-segment depression

• An abnormal heart-rate response

• Failure of blood pressure to rise appropriately

• A fall in systolic blood pressure

• Exercise-induced ventricular arrhythmias

• Angina at a low workload

• ST-segment depression persisting for more than 5 minutes after exercise

Conversely, individuals who achieve more than 10 metabolic equivalents, have a negative exercise ECG and a low-risk Duke Treadmill Score generally have a favourable prognosis and limited need for downstream testing or revascularization.

Arrhythmia evaluation

Exercise testing is indicated or reasonable in selected patients with suspected or known exercise-related rhythm disorders. It may be used to:

• Provoke and diagnose exercise-induced ventricular arrhythmias

• Assess the response to medical or ablation therapy

• Investigate suspected chronotropic incompetence

• Evaluate exercise-related symptoms suggestive of bradycardia or conduction disease

• Clarify the level of 2:1 atrioventricular block

• Determine whether symptoms in patients with first- or second-degree Mobitz type I atrioventricular block may improve with permanent pacing

• Establish and monitor the diagnosis of suspected long-QT syndrome

In patients with known or suspected exercise-induced ventricular arrhythmias, exercise testing is not a low-risk procedure. The physician should often remain in the room, and intravenous access may be appropriate.

Valvular disease

Exercise testing is particularly useful when symptoms and resting findings are discordant. Exercise may be combined with echocardiography to evaluate structural and physiological responses.

Examples include:

• Mitral stenosis with discordant symptoms and resting echocardiographic findings

• Severe aortic stenosis without reported symptoms

• Symptoms that appear disproportionate to the resting severity of aortic stenosis

• Chronic severe mitral or aortic regurgitation with equivocal symptoms

• Assessment of exercise capacity in patients with valvular disease seeking competitive athletic participation

In aortic stenosis, the purpose is principally to uncover symptoms, quantify functional limitation and evaluate the blood-pressure response rather than to interpret isolated ST-segment changes.

Athletes and exercise participation

Routine exercise testing for ischaemia is not recommended in asymptomatic adults or older athletes because of low positive predictive value and the frequency of false-positive results. Assessment should instead focus on symptoms, cardiovascular risk and the possibility of unrecognized structural or electrical disease.

Exercise testing may be reserved for symptomatic athletes or those considered at high CAD risk. It may also help evaluate exercise-induced arrhythmias, blood-pressure responses, symptoms, physical performance and the relationship between symptoms and training. Sport-specific protocols can improve the likelihood of reproducing the relevant physiological demands.

Exercise testing is not required before initiating moderate exercise, including in individuals at high cardiovascular risk. It may be considered in asymptomatic high-risk individuals planning to undertake vigorous exercise.

Patient selection and contraindications

Requirements for a useful diagnostic test

Interpretation of exercise ECG requires:

• An ECG that permits assessment of exercise-induced ST-segment changes.

• The ability to perform an adequate workload.

• A clinical question for which exercise information will affect management.

The test has no diagnostic value for obstructive CAD when baseline abnormalities prevent reliable ST-segment interpretation. Important examples include:

• Left bundle branch block

• Ventricular paced rhythm

• Wolff–Parkinson–White syndrome or other pre-excitation

• Resting ST-segment depression ≥0.1 mV

• Treatment with digitalis

Diagnostic accuracy is also affected by ventricular hypertrophy, resting ST–T abnormalities, intraventricular conduction disturbances, cardioactive or antiarrhythmic drugs and abnormal serum potassium levels.

Contraindications and situations requiring caution

The source material identifies the following as contraindications to exercise stress testing:

• Angina at rest within the preceding 48 hours

• Unstable rhythm

• Severe aortic stenosis

• Acute myocarditis

• Uncontrolled heart failure

• Severe pulmonary hypertension

• Active infective endocarditis

Exercise testing should not be performed in patients with symptomatic severe aortic stenosis. It should also be avoided in asymptomatic patients with a peak aortic velocity exceeding 5.0 m/s, because the severity of stenosis itself represents a reasonable indication for aortic valve replacement.

In patients with exercise-induced ventricular arrhythmias, the test should be approached as a potentially high-risk procedure, with appropriate supervision and, in many cases, intravenous access.

Clinical assessment and physical examination

A focused pre-test assessment should include:

• Pulse rate and regularity

• Resting blood pressure in the sitting and standing positions

• Lung auscultation, particularly in patients with dyspnoea, heart failure or pulmonary disease

• Cardiac auscultation, especially when heart failure or valvular disease is suspected

• Assessment of orthopaedic, neurological or other conditions that may limit exercise

The clinical history should establish the nature and reproducibility of symptoms, exertional capacity, prior CAD, arrhythmia history, medication use and potential non-cardiac limitations. The ability to achieve an adequate workload is essential because a test terminated prematurely by musculoskeletal limitation or deconditioning may be diagnostically nondiagnostic.

Test preparation and technical performance

ECG acquisition

A standard 12-lead ECG should be obtained before torso electrode placement. Torso placement of the limb electrodes can alter inferior lead complexes and may either mimic or conceal previous Q waves. A standing ECG should provide the reference for identifying exercise-induced changes.

During exercise, torso electrodes are positioned beneath the lateral clavicles for the arm leads and on the lower or upper rib cage for the leg leads. The original ECG recordings should be examined in addition to any magnified or signal-averaged display, because averaging can be distorted by respiratory variation, motion artefact, ventricular ectopy or transient conduction abnormalities.

Exercise protocol

The workload is increased in standardized increments, most commonly using a Bruce or modified Bruce treadmill protocol. Less intense protocols may be appropriate for older, sedentary or untrained individuals. In aortic stenosis, a Naughton or other low-level protocol with 1-metabolic-equivalent increments may be used.

The test is usually symptom-limited. It may be terminated because of:

• Limiting chest discomfort

• Severe dyspnoea

• Dizziness

• Severe fatigue

• Significant ST-segment depression

• A fall in systolic blood pressure

• Ventricular tachyarrhythmia

• Excessive hypertension

• Achievement of approximately 85% of the maximal predicted heart rate

In aortic stenosis, exercise should be stopped for limiting dyspnoea or fatigue at a low workload, angina, dizziness, a decrease in systolic blood pressure or complex ventricular ectopy. Minute-by-minute assessment of symptoms, blood pressure and rhythm is particularly important.

A medical professional should be present throughout the test, and resuscitation equipment should be available.

Medication considerations

Antianginal therapy can reduce the sensitivity of exercise testing when the objective is to diagnose ischaemia. If clinically feasible:

• Long-acting beta-blockers should be withheld for 2–3 days before testing.

• Long-acting nitrates, calcium antagonists and short-acting beta-blockers are generally withheld on the preceding day.

Medication discontinuation is not necessary when the purpose of testing is risk stratification in a patient with known CAD.

ECG interpretation

ST-segment depression

The conventional criterion for an abnormal ischaemic response is horizontal or downsloping ST-segment depression of at least 0.1 mV, or 1 mm, measured in three consecutive beats. The ST segment is measured 60–80 ms after the J point, using the PQ point as the isoelectric reference. At heart rates above 130 beats/min, the 60-ms post-J-point measurement is used.

The response should generally be present in at least three consecutive beats in two contiguous leads. Lateral precordial leads, particularly V5, are most useful for defining an ischaemic response. Inferior leads may assist in judging the extent of abnormalities when lateral leads are also affected, although isolated inferior ST depression is frequently falsely abnormal because of atrial repolarization.

ST-segment depression during recovery is clinically relevant and may have the same significance as changes occurring at peak exercise. Changes resolving within the first minute of recovery are associated with a favourable prognosis and a lower yield from subsequent diagnostic testing than abnormalities persisting beyond one minute.

ST-segment depression does not localize ischaemia to a specific coronary artery or vascular territory. Changes should be measured from the isoelectric line in patients with early repolarization rather than from the baseline ST elevation.

Non-diagnostic and non-specific findings

The following findings should be recorded but are not, in isolation, diagnostic of ischaemia:

• T-wave abnormalities

• Exercise-induced conduction disturbances

• Ventricular arrhythmias

• Junctional or upsloping ST-segment changes

A test that fails to achieve approximately 85% of the maximal predicted heart rate is generally considered nondiagnostic when performed for ischaemia assessment.

Clinical and haemodynamic context

ECG interpretation should be integrated with:

• Exercise duration

• Workload or metabolic equivalents

• Time to symptom onset

• Time to ST-segment depression

• Heart-rate–blood-pressure product

• Depth of ST depression

• Duration of post-exercise ST changes

• Blood-pressure response

• Presence and severity of symptoms

• Exercise-induced arrhythmias

A positive exercise ECG has different implications according to pre-test probability. False-positive results are particularly common in populations with a low likelihood of disease, including asymptomatic young men and premenopausal women without risk factors. Bayesian interpretation is therefore essential.

Diagnostic performance and limitations

Exercise ECG has relatively modest diagnostic accuracy for obstructive CAD, with reported sensitivity of 58% and specificity of 62% in the guideline material. Other source material describes overall sensitivity as approximately 75%, emphasizing that a negative test does not exclude CAD.

The test has several important limitations:

• It requires an interpretable resting ECG.

• It requires the patient to achieve an adequate workload.

• It cannot identify coronary plaque morphology or plaque vulnerability.

• It does not assess ischaemia beyond the workload actually achieved.

• It may be falsely positive in patients with low disease probability.

• It may be falsely negative in disease confined to the circumflex territory, which is relatively poorly represented on the surface ECG.

• Antianginal medication may reduce sensitivity.

• The positive predictive value depends strongly on disease prevalence and pre-test probability.

• Exercise imaging has greater diagnostic accuracy in both men and women.

Because of these limitations, exercise ECG should not be used as the preferred first-line diagnostic test for patients at intermediate or high risk with stable chest pain when CCTA or stress imaging is available.

Imaging alternatives and adjuncts

When the resting ECG is uninterpretable or when greater diagnostic accuracy is required, stress imaging should be used. Available modalities described in the source material include:

• Stress echocardiography

• Stress myocardial perfusion imaging with single-photon emission computed tomography

• Positron emission tomography perfusion imaging

• Stress cardiac magnetic resonance

• CCTA for anatomical assessment

Stress echocardiography can demonstrate new regional wall-motion abnormalities during exercise or dobutamine stress. Perfusion imaging identifies reversible defects by comparing stress and rest images. Cardiac magnetic resonance can assess ventricular structure and function, perfusion and areas of infarction.

Patients unable to exercise because of peripheral vascular or musculoskeletal disease, exertional dyspnoea or deconditioning may undergo pharmacological stress testing. Adenosine can increase flow preferentially in non-diseased coronary segments, whereas dobutamine increases myocardial oxygen demand. These pharmacological stressors may be paired with perfusion imaging, echocardiography or cardiac magnetic resonance.

High-risk stress-test results, regardless of symptom severity, should prompt either CCTA or invasive coronary angiography. Patients with a clearly negative exercise test generally have an excellent prognosis, and additional testing is not usually indicated in the absence of other high-risk features or refractory symptoms.

Exercise testing in specific electrophysiological disorders

Catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia typically occurs during intense emotional or physical stress. Resting ECG and standard cardiac testing are usually normal, while maximal exercise testing commonly provokes the arrhythmia. It often begins at heart rates above 120–130 beats/min with polymorphic premature ventricular complexes, progresses to non-sustained ventricular tachycardia and may evolve into bidirectional or polymorphic ventricular tachycardia.

The test is used to establish the diagnosis and assess response to beta-blockade.

Long-QT syndrome

Exercise testing is useful when long-QT syndrome is suspected and the resting corrected QT interval is borderline. Failure of a prolonged QT interval to shorten appropriately, or further prolongation during exercise, is characteristic of LQT1. LQT2 generally shows normal shortening, whereas LQT3 demonstrates more pronounced shortening. Beta-blockade can normalize these exercise-related responses.

Exercise testing may therefore assist diagnosis, risk stratification, treatment monitoring and the direction of genetic testing.

Exercise-induced ventricular arrhythmias

Exercise testing can provoke suspected exercise-induced ventricular arrhythmias and evaluate treatment response. In athletes, the endpoint is the presence or absence of significant ventricular arrhythmia during a level of exercise appropriate to the individual and the sport, rather than achievement of a particular maximal heart rate.

Serious ventricular arrhythmias during exercise commonly present as monomorphic ventricular tachycardia with a left bundle branch block pattern. Exercise may also identify patients with arrhythmogenic right-ventricular cardiomyopathy who are more likely to develop right-ventricular dysfunction or clinical heart failure requiring transplantation.

Bradycardia, conduction disease and chronotropic incompetence

Exercise ECG is reasonable in suspected chronotropic incompetence because it can establish the diagnosis and provide prognostic information. It is also useful in patients whose exertional symptoms suggest bradycardia or conduction disease, including unexplained 2:1 atrioventricular block.

In patients with exertional chest pain or dyspnoea and resting first-degree or Mobitz type I second-degree atrioventricular block, exercise testing may help determine whether permanent pacing should be considered.

Exercise testing in valvular disease

In aortic stenosis, the exercise test should be restricted to patients without reported symptoms or with symptoms that are at most equivocal, and who have no extracardiac limitation to exercise or contraindication to valve replacement.

The abnormal responses of greatest importance include:

• Development of angina

• Dizziness

• Limiting dyspnoea or fatigue at a low workload

• Failure of exercise capacity to meet age- and sex-related expectations

• A fall in systolic blood pressure

• Complex ventricular ectopy

A fall in systolic blood pressure of more than 10 mmHg from baseline to peak or low exercise tolerance is considered abnormal. Isolated ST-segment depression, particularly more than 2 mm, is common in severe aortic stenosis with left-ventricular hypertrophy and is non-specific.

In chronic severe mitral or aortic regurgitation, the principal role of exercise testing is to clarify functional capacity when symptoms are uncertain. Exercise testing combined with echocardiography is often preferred when structural and physiological responses need to be assessed together.

Acute and long-term management implications

Exercise ECG is a diagnostic and prognostic procedure rather than a treatment. Its findings may nevertheless alter management in several ways.

After a negative or low-risk test

Patients with clearly negative results and no other high-risk features generally have an excellent prognosis. Further testing is usually unnecessary unless symptoms are refractory, the test was technically inadequate or other clinical features remain concerning.

Individuals who achieve more than 10 metabolic equivalents with a negative ECG and low-risk Duke Treadmill Score usually require little downstream testing or revascularization.

After a high-risk test

Marked ischaemia at a low workload, a high-risk Duke Treadmill Score, severe exercise limitation, abnormal blood-pressure response, prolonged recovery ST depression or exercise-induced ventricular arrhythmias should lead to further anatomical or functional evaluation. CCTA or invasive coronary angiography is recommended for patients with high-risk stress-test results.

Treatment assessment

Serial exercise testing can assess the response to:

• Antianginal medication

• Coronary revascularization

• Cardiac rehabilitation

• Catheter ablation

• Surgical treatment

Useful serial measures include the workload or heart rate at onset of angina or ST depression and the rate–pressure product at the onset of ischaemia. These parameters are selected partly because of their reproducibility. Peak oxygen consumption is more reproducible, but cardiopulmonary exercise testing is not performed routinely in all settings.

In exercise-induced ventricular arrhythmias, treatment response is assessed by determining whether significant arrhythmias persist during an appropriate level of exertion.

Prognosis and follow-up

Prognostic variables

The most consistent prognostic marker is maximal exercise capacity, whether expressed as exercise duration, achieved workload or metabolic equivalents. Its prognostic importance persists regardless of whether the test ends because of dyspnoea, fatigue or angina.

Additional adverse prognostic features include:

• Exercise-induced ST-segment depression, particularly when extensive or marked

• Angina or severe ST depression at a low workload

• Abnormal heart-rate response

• Failure of systolic blood pressure to increase

• A fall in systolic blood pressure

• Ventricular tachyarrhythmia

• Prolonged persistence of ST-segment depression during recovery

• A high-risk Duke Treadmill Score

A negative exercise test does not exclude all CAD, but it makes left-main or three-vessel disease extremely unlikely in the source material. Persistent symptoms or other high-risk features should therefore override reassurance from an otherwise negative test.

Follow-up testing

Repeat exercise testing may be used when it will affect management, including:

• Reassessment after therapeutic intervention

• Monitoring of exercise-induced arrhythmias

• Evaluation of progression or change in symptoms

• Assessment of exercise capacity in valvular disease

• Follow-up of athletes with exercise-related symptoms or arrhythmias

• Serial assessment in selected congenital heart disease populations

In adults with congenital heart disease, cardiopulmonary exercise testing provides broader information than exercise ECG alone, including peak oxygen consumption, ventilatory efficiency, chronotropic and blood-pressure responses, exercise-induced arrhythmias and oxygen desaturation. These variables correlate with morbidity and mortality, and serial testing should form part of long-term follow-up protocols when appropriate.

Guideline recommendations

Summary

Exercise ECG remains a valuable physiological and prognostic test when used selectively. Its strengths are the direct assessment of exercise capacity, symptoms, haemodynamic responses and exercise-induced arrhythmias. Its principal limitation is the relatively low diagnostic accuracy for obstructive CAD, particularly compared with CCTA and functional imaging.

A high-quality test requires an interpretable resting ECG, adequate exercise capacity, careful supervision and integrated interpretation of symptoms, workload, ECG findings, blood pressure, heart rate and recovery responses. Exercise ECG should principally support risk stratification and management decisions, while anatomical or stress-imaging techniques should generally be preferred when definitive diagnosis of CAD is required.