A. Laboratory Findings

Serum lipid levels should be determined in all patients with suspected angina. Anemia and diabetes may also be investigated if clinically appropriate.

B. Electrocardiography

The resting ECG is normal in about a quarter of patients with angina. In the remainder, abnormalities include old myocardial infarction, nonspecific ST-T changes, atrioventricular or intraventricular conduction defects, and changes of left ventricular hypertrophy. During anginal episodes, the characteristic electrocardiographic change is horizontal or downsloping ST segment depression that reverses after the ischemia disappears. T wave flattening or inversion may also occur. Less frequently, ST segment elevation is observed; this finding suggests severe (transmural) ischemia and often occurs with coronary spasm.

C. Exercise Electrocardiography

Exercise testing is the most useful noninvasive procedure for evaluating the patient with angina. Ischemia that is not present at rest is detected by precipitation of typical chest pain or ST segment depression (or, rarely, elevation). Exercise testing is often combined with scintigraphic studies or echocardiography (see below), but in patients without baseline ST segment abnormalities or in whom anatomic localization is not necessary, the exercise ECG should be the initial procedure because of considerations of cost and convenience.

Exercise testing can be done on a motorized treadmill or with a bicycle ergometer. A variety of exercise protocols are utilized, the most common being the Bruce protocol, which increases the treadmill speed and elevation every 3 minutes until limited by symptoms. At least two electrocardiographic leads should be monitored continuously.

1. Precautions and risks  - The usually quoted risk of exercise testing is one infarction or death per 1000 tests, but individuals who continue to have pain at rest or minimal activity are at higher risk and should not be tested. Many of the traditional exclusions, such as recent myocardial infarction or congestive heart failure, are no longer employed if the patient is stable and ambulatory, but aortic stenosis remains a contraindication. While most tests are carried to a symptom-limited end point (except submaximal testing early postinfarction), the test should be terminated when hypotension, significant ventricular or supraventricular arrhythmias, more than mild to moderate angina, or more than 3- to 4-mm ST segment depression occurs.

2. Indications  - Exercise testing is employed (1) to confirm the diagnosis of angina; (2) to determine the severity of limitation of activity due to angina; (3) to assess prognosis in patients with known coronary disease, including those recovering from myocardial infarction, by detecting groups at high or low risk; (4) to evaluate responses to therapy; and (5) less successfully, to screen asymptomatic populations for silent coronary disease. The latter application is controversial. Because false-positive tests often exceed true positives, leading to much patient anxiety and self-imposed or mandated disability, exercise testing of asymptomatic individuals should be done only for those at high risk (usually a strong family history of premature coronary disease or hyperlipidemia), those whose occupations place them or others at special risk (eg, airline pilots), and older individuals commencing strenuous activity.

3. Interpretation  - The usual electrocardiographic criterion for a positive test is 1 mm (0.1 mV) horizontal or downsloping ST segment depression (beyond baseline) measured 80 ms after the J point. By this criterion, 60-80% of patients with anatomically significant coronary disease will have a positive test, but 10-30% of those without significant disease will also be positive. False-positives are uncommon when a 2-mm depression is present. Additional information is inferred from the time of onset and duration of the electrocardiographic changes, their magnitude and configuration, blood pressure and heart rate changes, the duration of exercise, and the presence of associated symptoms. In general, patients exhibiting more severe ST segment depression (> 2 mm) at low workloads (< 6 minutes on the Bruce protocol) or heart rates (< 70% of age-predicted maximum) - especially when the duration of exercise and rise in blood pressure are limited or when hypotension occurs during the test - have more severe disease and a poorer prognosis. Depending on symptom status, age, and other factors, such patients should be referred for coronary arteriography and possible revascularization. On the other hand, less impressive positive tests in asymptomatic patients are often “false-positives.” Therefore, exercise testing results that do not conform to the clinical picture should be confirmed by stress scintigraphy or echocardiography.

D. Scintigraphic Assessment of Ischemia

Two nuclear medicine studies provide additional information about the presence, location, and extent of coronary artery disease.

1. Myocardial perfusion scintigraphy  - This test provides images in which radionuclide uptake is proportionate to blood flow at the time of injection. Thallium-201, technetium-99m sestamibi, and tetrafosmin are most frequently used. Areas of diminished uptake reflect relative hypoperfusion (compared to other myocardial regions). If the radiotracer is injected during exercise or dipyridamole- or adenosine-induced coronary vasodilation, scintigraphic defects indicate a zone of hypoperfusion that may represent either ischemia or scar. If the myocardium is viable, as relative blood flow equalizes over time or during a scintigram performed under resting conditions, these defects tend to “fill in” or reverse, indicating reversible ischemia. Defects observed when the radiotracer is injected at rest or still present 3-4 hours after an injection during exercise or pharmacologic vasodilation (intravenous adenosine or dipyridamole) usually indicate myocardial infarction (old or recent) but may be present with severe ischemia. Occasionally, other conditions, including infiltrative diseases (sarcoidosis, amyloidosis), left bundle branch block, and dilated cardiomyopathy, may produce resting or persistent perfusion defects.

In experienced laboratories, stress perfusion scintigraphy is positive in 75-90% of patients with anatomically significant coronary disease and in 20-30% of those without it. False-positive tests may occur as a result of diaphragmatic attenuation or, in women, attenuation through breast tissue. Tomographic imaging (SPECT) can reduce the severity of artifacts. Gated imaging allows for analysis of ventricular size, ejection fraction, and regional wall motion.

Myocardial scintigraphy is indicated (1) when the resting ECG makes an exercise ECG difficult to interpret (LBBB, baseline ST-T changes, low voltage, etc), (2) for confirmation of the results of the exercise ECG when they are contrary to the clinical impression (eg, a positive test in an asymptomatic patient), (3) to localize the region of ischemia, (4) to distinguish ischemic from infarcted myocardium, (5) to assess the completeness of vascularization following bypass surgery or coronary angioplasty, or (6) as a prognostic indicator in patients with known coronary disease.

2. Radionuclide angiography  - This procedure images the left ventricle and measures its ejection fraction and wall motion. In coronary disease, resting abnormalities usually represent infarction, and those that occur only with exercise usually indicate stress-induced ischemia. Normal subjects usually exhibit an increase in ejection fraction with exercise or no change; patients with coronary disease may exhibit a decrease. Exercise radionuclide angiography has approximately the same sensitivity as thallium-201 scintigraphy, but it is less specific in older individuals and those with other forms of heart disease. The indications are similar to those for thallium-201 scintigraphy.

3. Positron emission tomography (PET)  - PET utilizes positron emitting agents to demonstrate either perfusion or metabolism of myocardium. PET can accurately distinguish transiently dysfunctional (“stunned”) myocardium from scar by showing persistent glycolytic metabolism with the tracer fluorodeoxyglucose (FDG) in regions with reduced blood flow. A nearby cyclotron is required to produce this tracer, but the newer SPECT camera can provide acceptable images without the more expensive PET technology.

E. Echocardiography

Echocardiography can image the left ventricle and reveal segmental wall motion abnormalities, which may indicate ischemia or prior infarction. It is a convenient technique for assessing left ventricular function, which is an important indicator of prognosis and determinant of therapy. Echocardiograms performed during supine exercise or immediately following upright exercise may demonstrate exercise-induced segmental wall motion abnormalities as an indicator of ischemia. This technique requires considerable expertise; however, in experienced laboratories, the test accuracy is comparable to that obtained with scintigraphy - though a higher proportion of tests are technically inadequate. Pharmacologic stress with high-dose (20-40 ug/kg/min) dobutamine can be used as an alternative to exercise. Echo contrast agents allow for perfusion imaging and may improve the diagnostic accuracy of this form of testing.

F. Newer Imaging Modalities

Many new imaging techniques have been developed, but their application in cardiovascular disease remains to be determined. Computed tomography (CT scan) can image the heart and, with contrast medium, the vascular system, but the relatively slow speed of most instruments limits its utility. The main application of CT is the evaluation of pericardial disease. Ultrafast or electron beam CT (EBCT) involves a specially designed instrument with high temporal resolution. Its availability is limited, but it provides excellent assessments of cardiac structure and function. EBCT is increasingly being used to detect and quantify coronary artery calcification, but proper application of this highly sensitive test is uncertain. False-negative studies may occur in patients under 50 years of age, and positive studies in older patients do not necessarily provide a quantitative assessment of the severity of coronary arteriosclerosis. Thus, although this test can stratify patients into lower and higher risk groups, the appropriate management of individual patients with asymptomatic coronary artery calcification - beyond aggressive risk factors modification - is unclear.

Cardiac magnetic resonance imaging (MRI) is an evolving modality that provides high-resolution images of the heart and great vessels without radiation exposure or use of iodinated contrast media. It provides excellent anatomic definition, permitting assessment of pericardial disease, neoplastic disease of the heart, myocardial thickness, chamber size, and many congenital heart defects. It is the best noninvasive test for nonemergently evaluating dissection of the aorta. Rapid acquisition sequences can produce excellent cine-mode images demonstrating left ventricular function and wall motion, and it is thus a useful alternative when the echocardiogram is suboptimal. Recent advances have been made in imaging the proximal coronary arteries and assessing myocardial perfusion with paramagnetic contrast agents, but these applications remain investigational.

G. Ambulatory Electrocardiographic Monitoring

With current ambulatory electrocardiographic recorders and with trained technicians, episodes of ischemic ST segment depression can be monitored. In patients with coronary artery disease, these episodes usually signify ischemia, even when asymptomatic (“silent”). In many, silent episodes are more frequent than symptomatic ones. In most cases, they occur in patients with other evidence of ischemia, and they respond to the same treatments, so that the role of ambulatory monitoring is unclear, as is the benefit of abolishing all such episodes in patients who are otherwise being managed properly.

H. Coronary Angiography

Selective coronary arteriography is the definitive diagnostic procedure for coronary artery disease. It can be performed with low mortality (about 0.1%) and morbidity (1-5%), but the cost is high, and with currently available noninvasive techniques it is usually not indicated solely for diagnosis.

Coronary arteriography should be performed in the following groups:

(1) Patients being considered for coronary artery revascularization because of limiting stable angina who have failed to improve on an adequate medical regimen.

(2) Patients in whom coronary revascularization is being considered because the clinical presentation (unstable angina, postinfarction angina, etc) or noninvasive testing suggests high-risk disease (see Indications for Revascularization).

(3) Patients with aortic valve disease who also have angina pectoris, in order to determine whether the angina is due to accompanying coronary disease. Coronary angiography is also performed in asymptomatic older patients undergoing valve surgery so that concomitant bypass may be done if the anatomy is propitious.

(4) Patients who have had coronary revascularization with subsequent recurrence of symptoms, to determine whether bypass grafts or native vessels are occluded.

(5) Patients with cardiac failure in whom a surgically correctable lesion, such as left ventricular aneurysm, mitral regurgitation, or reversible ischemic dysfunction, is suspected.

(6) Patients surviving sudden death or with symptomatic or life-threatening arrhythmias in whom coronary artery disease may be a correctable cause.

(7) Patients with chest pain of uncertain cause or cardiomyopathy of unknown cause.

Coronary arteriography visualizes the location and severity of stenoses. Narrowing greater than 50% of the luminal diameter is considered clinically significant, although most lesions producing ischemia are associated with narrowing in excess of 70%. This information has important prognostic value, since mortality rates are progressively higher in patients with one-, two-, and three-vessel disease and those with left main coronary artery obstruction (ranging from 1% per year to 25% per year). In those with strongly positive exercise ECGs or scintigraphic studies, three-vessel or left main disease may be present in 75-95% depending upon the criteria employed. Coronary arteriography also shows whether the obstructions are amenable to bypass surgery or percutaneous transluminal coronary angioplasty (PTCA).

Coronary angiography may underestimate the degree of atherosclerosis because it images only the lumen of the vessel. If there is concentric plaque with arterial enlargement (remodeling), then the lumen may appear relatively normal. Intravascular ultrasound (IVUS) utilizes a small ultrasound transducer that can be positioned within the artery and image beneath the endothelial surface. This technique is useful when the angiogram is equivocal as well as for assessing the results of angioplasty or stenting.

I. Left Ventricular Angiography

Left ventricular angiography is usually performed at the same time as coronary arteriography. Global and regional left ventricular function are visualized, as well as mitral regurgitation if present. Left ventricular function is the major determinant of prognosis in stable coronary disease and of the risk of bypass surgery.

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