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Exercise is preferred to drugs for increasing cardiac demand because it more closely replicates ischemia-inducing stressors. Usually, a patient walks on a conventional treadmill, following the Bruce protocol or a similar exercise schedule, until the target heart rate is reached or symptoms occur. The Bruce protocol (most commonly used) increases treadmill speed and slope incrementally at roughly 3-minute intervals.

Pharmacologic stress testing is usually used when patients cannot walk on a treadmill long enough to reach their target heart rate because of deconditioning, musculoskeletal disorders, obesity, peripheral arterial disease, or other disorders. Drugs used include IV dipyridamole, adenosine, regadenoson, and dobutamine.

Dipyridamole augments endogenous adenosine, causing coronary artery vasodilation. It increases myocardial blood flow in normal coronary arteries but not in arteries distal to a stenosis, creating a “steal” phenomenon from stenosed arteries and an imbalance in perfusion. Dipyridamole-induced ischemia or other adverse effects (eg, nausea, vomiting, headache, bronchospasm) occur in about 10% of patients, but these effects can be reversed by IV aminophylline. Severe reactions occur in < 1% of patients. Contraindications include asthma, acute phase myocardial infarction (MI), unstable angina pectoris, critical aortic stenosis, and systemic hypotension (systolic BP < 90 mm Hg).

Adenosine has the same effect as dipyridamole but must be given in a continuous IV infusion because it is rapidly degraded in the plasma. Adverse effects include transient flushing, chest pain, and tachycardia, which can be reversed by terminating the infusion.

Regadenoson is a more selective adenosine agonist than either dipyridamole or adenosine and is non-inferior for the diagnosis of ischemia with fewer adverse effects and greater ease of administration.

Dobutamine is an inotrope, chronotrope, and vasodilator used mainly when dipyridamole and adenosine are contraindicated (eg, in patients with asthma or 2nd-degree atrioventricular block) and when echocardiography is used to image the heart. Dobutamine must be used with caution in patients who have severe hypertension or arrhythmia, left ventricular outflow tract obstruction, multiple previous MIs, or acute MI.

ECG is always used with stress testing to diagnose coronary artery disease and help determine prognosis. Stress ECG alone (ie, without radionuclide imaging or echocardiography) is most useful in patients with

• Intermediate likelihood of CAD based on age and sex

• Normal ECG at rest

Diagnosis involves assessment of ST-segment response (a measure of global subendocardial ischemia), BP response, and the patient’s symptoms.

Average sensitivity is 67%; average specificity is 72%. Sensitivity and specificity are lower in women partly because incidence of CAD is lower in young and middle-aged women. Prognosis worsens with depth of ST depression.

Radionuclide myocardial perfusion imaging is more sensitive (85 to 90%) and specific (70 to 80%) than ECG stress testing. Combining findings from both tests increases sensitivity for coronary artery disease.

Myocardial perfusion imaging is particularly useful for patients with

• Baseline ECG abnormalities that may interfere with interpretation of ECG changes during a stress test (eg, bundle branch block, fixed-rate pacemakers, digitalis effects).

• High probability of false-positive results on exercise ECGs (eg, premenopausal women, patients with mitral valve prolapse)

This imaging test can help determine the functional significance of coronary artery stenosis, identified by coronary angiography, when surgeons are choosing lesions to bypass or dilate via percutaneous transluminal coronary angioplasty.

Echocardiography is useful when information about more than just perfusion is needed. Echocardiography detects wall motion abnormalities that are a sign of regional ischemia and, using Doppler techniques, helps evaluate valvular disorders that may contribute to or result from ischemia or valvular disorders unrelated to ischemia but which deserve concomitant evaluation.

The echocardiogram is typically obtained immediately before and after an exercise treadmill test or during dobutamine infusion.

Echocardiography is relatively portable, does not use ionizing radiation, has a rapid acquisition time, and is inexpensive, but it is difficult to carry out in patients with obesity and in patients with COPD and lung hyperinflation. Done by experts, stress echocardiography has a predictive value similar to that of stress myocardial radionuclide perfusion testing.

Stress hemodynamic echocardiography is considered for selected individuals for diagnosis of heart failure with preserved ejection fraction.

Radionuclide ventriculography is occasionally used with exercise stress testing instead of echocardiography to assess exercise ejection fraction (EF), the best prognostic indicator in patients with coronary artery disease.

Normally, EF is ≥ 5 percentage points higher during exercise than at rest. Ventricular dysfunction (eg, due to valvular heart disorders, cardiomyopathy, or CAD) can decrease exercise EF below baseline or prevent it from increasing.

In patients with CAD, the 8-year survival rate is 80% with an exercise EF of 40 to 49%, 75% with an exercise EF of 30 to 39%, and 40% with an exercise EF of < 30%.