Stress testing is one of the most widely used tools in cardiology. It provides diagnostic and prognostic information in patients with suspected or known coronary heart disease, and is a useful tool for assessing the adequacy of therapy. Stress testing can also objectively assess the functional capacity of a patient, and help determine the nature of a patient’s functional limitations.

Indications
The most common (and, perhaps, most useful) indication for stress testing is to determine whether a patient’s symptoms relate to underlying coronary artery disease. For patients in whom the diagnosis of CAD is already certain, stress testing may be useful to:

• assess risk and determine long-term prognosis
• assess exercise capacity
• evaluate the efficacy of therapy
• assist in therapeutic decision making (i.e., determine who may benefit from cardiac catheterization and revascularization)
• detect exercise-related arrhythmias
• localize a region of ischemia in order to target percutaneous revascularization

Contraindication
There are small but real risks associated with stress testing, including myocardial infarction ( MI ), serious arrhythmias, and death (approximate rate of 1 in 2,500 tests). Most of these complications occur in patients with certain high-risk markers; therefore, patients should be carefully screened before undergoing exercise testing to ensure that no contraindications exist (see Table 6-1).

Testing Madalities
Stress testing can be performed in several ways (Table 6-2). The stress can be induced by exercise (either walking on a treadmill or riding a bicycle) or by pharmacological means with dobutamine or coronary vasodilators. Treadmill exercise is the best-standardized modality and allows for more flexible protocols, as speed and incline can be varied independently. The Bruce protocol is the most commonly used and consists of incremental increases in the speed and slope of the treadmill every three minutes. Bicycle testing may, however, be better tolerated in patients who have orthopedic or balance problems. The aim of the exercise is to increase myocardial oxygen demand (MV0₂). In patients with coronary artery disease (CAD), the increased MV0₂ may exceed the ability of the coronary arteries to supply oxygenated blood, resulting in ischemia.

Dobutamine produces an increase in heart rate, contractility, and blood pressure, thereby mimicking exercise and increasing MV0 ₂. Dipyridamole or adenosine cause coronary vasodilation preferentially in normal coronary arteries. This results in a flow mismatch with blood flow in normal coronary arteries increased relative to diseased coronary arteries. Pharmacological stress testing with these agents yields sensitivities and specificities comparable to Exercise stress testing.
Pharmacological stress is not without risk; dobutamine can induce ventricular arrhythmias and precipitate myocardial ischemia, while dipyridamole can cause bronchospasm.

Monitoring Modalities
All patients who undergo stress testing are assessed for symptoms and have continuous ECG monitoring to identify ischemic changes (ST depression or elevation) or arrhythmias. The sensitivity and specificity of stress testing can be improved with the use of echocardiographic or nuclear imaging to identify objectively areas of myocardial ischemia.

The isotopes used in myocardial perfusion imaging are thallium-20l (²⁰¹TI) and technetium-99m (^99mTc) sestamibi. Sestamibi is a newer agent that has superior image quality, and allows for the assessment of left ventricular function as well as ischemia. After intravenous injection, these isotopes are taken up by viable myocardial cells in quantities proportional to their regional blood flow. Regions of the myocardium that are well perfused appear brighter on nuclear imaging than regions that are poorly perfused (because of CAD) (Figure 6-1). When used during stress testing, nuclear or echocardiographic imaging is performed at both rest and at peak exercise.

Choice of testing Madalities (Physiological vs. Pharmacological)
In general, if a patient can exercise, an exercise test is preferred over a pharmacological stress test (see Figure 6-2) because it is a more physiological study. Pharmacological stress testing is employed when the patient is unable to exercise adequately. With exercise or dobutamine stress testing, the patient must attain at least 85% of his/her maximum predicted heart rate (maximum predicted heart rate = 220 - age) in order to achieve a sufficient level of myocardial stress to precipitate ischemia. When dipyridamole or adenosine is used as the stress modality, it is presumed that maximum coronary vasodilation occurs with the standard dose, and a heart rate response is not required.

The level of physiological stress achieved can be compared between different exercise protocols and related to routine daily activities by reporting the level of stress in terms of metabolic equivalents (METs) (see Table 6-3). One MET equals the body’s oxygen requirement at rest (~ 3.5 mLO₂/min/kg body weight).

Choice of monitoring modalities (ECG alone vs. Imaging)
If a patient can exercise and has no significant ST segment abnormalities on his/her resting ECG, then ECG monitoring alone is usually adequate. In patients with abnormal resting ECGs (left bundle branch block [LBBB], left ventricular hypertrophy, digoxin effect, paced rhythms, persistent ST segment depression), the ECG is not adequate to identify ischemia, and an additional imaging modality is necessary. When pharmacological stress testing is used, an imaging modality is always necessary because of the low sensitivity of drug-induced ST segment changes. The use of echocardiographic or nuclear imaging improves the sensitivity and specificity of the test in these settings. The decision as to which imaging modality should be employed depends on the expertise of the institution. The reported sensitivities among the various modalities are similar (see Table 6-4).

Interpreatation of exercise ECG testing
ST segment depression is the most common electrocardiographic manifestation of ischemia. Other stress-induced ECG findings suggestive of ischemia include ST segment elevation, ventricular ectopy or arrhythmias, QRS widening, and increased R wave amplitude.
Several different types of ST segment changes may be seen, although horizontal or down-sloping ST depressions are the most specific (see Figure 6-3). Although chest pain occurs only in approximately 1/3 of stress tests, its presence increases the likelihood of underlying coronary heart disease.

When echocardiography or nuclear imaging are performed, ischemia is defined as a region of myocardium that appears normal at rest but abnormal with exercise.
Infarction is a region that appears abnormal at both rest and exercise. Either of these findings is strong evidence of CAD.

Certain findings during stress testing are markers for adverse prognosis. These include:

• ST segment depression of ≥2 mm or in ≥5 leads
• ST segment elevation
• angina pectoris
• ventricular tachycardia
• exercise-induced hypotension (> 20mmHg drop in systolic blood pressure [SBP])
• low exercise capacity (≤ 5 MET level)

The theory of conditional probability, or Bayes’ theorem, is an integral component of the interpretation of stress testing when it is used for diagnosing ischemic heart disease. This theorem states that the post-test probability of a particular disease depends upon the incidence of the disease in the population being studied.

That is, an abnormal stress test in a person with a very low likelihood of having CAD is probably a false positive test, and a negative test in a person with a very high probability of having CAD is likely a false negative test.

Therefore, stress testing for the diagnosis of CAD is most helpful in patients who have an intermediate probability of CAD.

Stress testing in Women
Women under the age of 55 to 60 years often have “false-positive ST depression,” i.e., ST segment depression in relation to exertion that is not due to epicardial coronary artery disease. Consequently, other exercise variables, such as exercise time and hypotension, must be considered when diagnosing coronary heart disease in women. Given the lower prevalence of ischemic heart disease in women as compared with men, all modalities of stress testing are less accurate in this population.

Cardiopulmonary stress testing
Cardiopulmonary exercise testing (CPET) measures respiratory gas exchange during treadmill or bicycle exercise protocols. It uses these data to provide information regarding peak oxygen uptake, anaerobic threshold, and minute ventilation. Indications for CPET include:

• objective assessment of functional capacity
• determination of the appropriateness and timing of cardiac transplantation
• determination whether a patient’s dyspnea or low exercise capacity is the result of cardiac disease, pulmonary disease, deconditioning, or poor motivation.