Laboratory Studies
Investigative studies
Urinary proton nuclear magnetic resonance (1H NMR) spectroscopy–based metabolomic profiling appears to have the potential for identifying diagnostic biomarkers in the investigation of unstable angin pectoris metabolic signatures. [16]
Investigators have demonstrated enhanced expression of toll-like receptors 2 and 4 (TLR-2 and TLR-4) on platelets in patients with acute coronary syndrome, which has potential clinical implications for prophylactic and therapeutic targets. [17]
Chest Radiography
Chest radiograph findings are usually normal in patients with angina pectoris. However, they may show cardiomegaly in patients with previous MI, ischemic cardiomyopathy, pericardial effusion, or acute pulmonary edema. Calcification of coronary arteries frequently correlates with major coronary artery disease. [18]
Exercise Stress Testing
Graded exercise stress testing is the most widely used test for the evaluation of patients presenting with chest pain. In patients with established stable angina pectoris, it also can provide prognostic information about the extent of disease.
Exercise stress testing can be performed alone and in conjunction with echocardiography or myocardial perfusion scintigraphy tests. Stress echocardiography has an overall sensitivity of 78% and specificity of 86%; myocardial perfusion scintigraphy has an overall sensitivity of 83% and specificity of 77%. Exercise stress testing alone generally has somewhat lower sensitivity and specificity, but it is cheaper and therefore is a reasonable choice in those with a low probability of disease. [19]
These test results must be interpreted in the context of the likelihood of the presence of coronary artery disease determined from the patient's history and physical examination findings. In a population with low prevalence, the predictive abilities of these tests are low; however, in patients with a high likelihood of coronary artery disease, the predictive value is much higher.
The frequency of infarction or death is 1 case per 10,000 stress tests. Absolute contraindications include symptomatic cardiac arrhythmias, severe aortic stenosis, acute MI within the previous 2 days, acute myocarditis, or pericarditis. Discontinue the exercise stress test in the presence of chest pain, a drop in systolic blood pressure of more than 10 mm Hg, severe shortness of breath, fatigue, dizziness or near syncope, ST depression of more than 2 mm, ST elevation of at least 1 mm without diagnostic Q waves, or development of ventricular tachyarrhythmia.
Stress Echocardiography
Stress echocardiography can be used to evaluate segmental wall motion during exercise. It detects changes in regional wall motion that occur during myocardial ischemia. Normal myocardium becomes hyperdynamic during exercise; ischemic segments become hypokinetic or akinetic.
Stress echocardiography has the advantage of simultaneous evaluation of LV function, cardiac dimensions, and valvular disease. It is especially useful in patients with baseline ECG abnormalities and those with systolic murmurs suggestive of aortic stenosis or hypertrophic cardiomyopathy.
It is also helpful for localizing ischemia and evaluating its severity.
Signs of severe coronary artery disease during exercise stress echocardiography include LV dilation, a decrease in global systolic function, and new or worsening mitral regurgitation. However, with dobutamine stress echocardiography, even in patients with severe coronary artery disease, the LV cavity may not dilate and global systolic function may improve. A major problem with stress echocardiography is the technical difficulty with obtaining adequate images in some patients.
Nuclear Imaging
Myocardial perfusion scintigraphy
Thallium Tl 201 and technetium Tc 99m sestamibi are the most frequently used myocardial perfusion scintigraphy tests. These tests are especially useful in patients with baseline ECG abnormalities, to localize the region of ischemia, and as prognostic indicators. The presence of increased lung uptake upon thallium imaging is associated with a poor prognosis. Increased lung uptake, together with poststress dilation of the LV and multiple perfusion defects, is suggestive of either left main coronary artery disease or severe 3-vessel disease. The number of affected myocardial segments is predictive of long-term survival. Smaller perfusion defects are usually associated with peripheral coronary artery lesions, which are associated with a better prognosis. The absence of perfusion defects even in the presence of symptoms indicates an excellent prognosis.
Computed Tomography Scanning
In relatively recent years, coronary artery calcium (CAC) scoring by fast computed tomography (CT) has become more popular in clinical practice for risk assessment of patients with chest pain. Currently, electron-beam computed tomography (EBCT) and multi-detector computed tomography (MDCT) are the primary fast CT methods for CAC measurement. However, some controversy exists about the usefulness of this test. [20]
In asymptomatic patients, analysis of the data from CAC scoring in patients with an intermediate Framingham risk score reveals that for a score of 400 or more, the patient’s 10-year CAD risk would achieve a risk equivalent status similar to that noted with diabetes or peripheral arterial disease. [21] Thus, finding a high CAC score in asymptomatic patients with an intermediate Framingham risk score (10-20% risk of CAD in 10 y) could be useful by resulting in a more aggressive management approach. However, unselected screening is of limited clinical value in asymptomatic patients who have a low Framingham risk score. On the other hand, assessment of CAC in asymptomatic patients with a high Framingham risk score (>20% risk of CAD in 10 y) has limited value since, based on current guidelines, these patients should be treated aggressively irrespective of their CAC scoring.
In symptomatic patients, exclusion of measurable CAC may be an effective tool before undertaking invasive diagnostic procedures or hospital admission. Patients with CAC scores of less than 100 have a low probability (< 2%) of abnormal perfusion on nuclear stress tests, and a low probability (< 3%) of obstructive CAD (>50% stenosis) on cardiac catheterization. Studies of large numbers of symptomatic patients demonstrated that the absence of CAC has a high negative predictive value of 96-100%. Thus, an individual with no coronary calcium (score _ 0) can be told with a high level of confidence that he or she has no obstructive angiographic coronary disease.
In patients with documented CAD, clinical monitoring of CAC progression through serial fast CT scanning to assess progression or regression of CAD is not recommended at this time.
Because most of current data regarding CAC are collected from patient population of mostly white men, the guidelines suggest caution in applying these findings to women and ethnic minorities.
CT Angiography
In a 2008 study of 79 patients with stable angina pectoris, all patients underwent both dual-source computed tomography coronary angiography (CTCA) with quantitative CT coronary angiography (QCT) and coronary angiography with intracoronary fractional flow reserve (FFR) measurement of discrete coronary stenoses. [22] A total of 89 stenoses were evaluated which demonstrated that correlation between QCT and QCA with FFR measurement was weak (R values of -0.32 and -0.30, respectively). Although correlation between QCT and QCA was statistically significant, this correlation was only moderate (R = 0.53; p < 0.0001). This study demonstrated that anatomical assessment of the hemodynamic significance of coronary stenoses determined by visual CTCA, CCA, or QCT or QCA does not correlate well with the functional assessment of FFR.
Bamberg et al found that, in patients with acute chest pain and an inconclusive initial evaluation (nondiagnostic electrocardiographic findings, negative cardiac biomarkers), age and gender can serve as simple criteria to select patients who would derive the greatest diagnostic benefit from coronary computed tomographic angiography (CTA). In an observational cohort study in 368 low-risk patients, positive findings on 64-slice coronary CTA led to restratification to high risk, and negative findings led to restratification to very low risk, in men younger than 55 years and women younger than 65 years. In contrast, in women older than 65 years and men older than 55 years, a negative result on CTA did not result in restratification to a low-risk category. [23]
Electrocardiography
ECG is useful for evaluating persons with angina pectoris; however, findings are variable among patients.
Approximately 50% of patients with angina pectoris have normal findings after a resting ECG. However, abnormalities such as evidence for prior MI, intraventricular conduction delay, various degrees of atrioventricular block, arrhythmias, or ST-T–wave changes may be seen.
During an attack of angina pectoris, 50% of patients with normal findings after resting ECG show abnormalities. A 1-mm or greater depression of the ST segment below the baseline, measured 80 milliseconds from the J point, is the most characteristic change. Reversible ST-segment elevation occurs with Prinzmetal angina. Some patients with coronary artery disease may show pseudonormalization of the resting ECG ST-T–wave abnormalities during episodes of chest pain.
Exercise with ECG monitoring
Exercise with ECG monitoring alone is the initial procedure of choice in patients without baseline ST-segment abnormalities or in whom anatomic localization of ischemia is not a consideration. Note the following:
-
Horizontal or down-sloping ST-segment depression of at least 1 mm, measured 80 milliseconds from the J point, is considered the characteristic ischemic response.
-
ST-segment depression of more than 2 mm at a low workload or that persists for more than 5 minutes after termination of exercise and a failure of blood pressure to rise or an actual drop in blood pressure are signs of severe ischemic heart disease and a poor prognosis.
-
Withhold beta-blockers for approximately 48 hours before the stress test, whenever possible. Patients on digoxin and those with LV hypertrophy with repolarization abnormalities more often show positive results. Exercise stress tests have lower sensitivity and specificity in women and in patients with left bundle-branch block.
-
Pharmacologic agents (eg, dobutamine, dipyridamole, adenosine) can be used in patients who are unable to exercise.
Ambulatory ECG monitoring
Ambulatory ECG monitoring can be used for diagnostic purposes in patients with chest pain suggestive of Prinzmetal angina but is primarily used to evaluate the frequency of silent ischemia. Silent ischemia has been shown to be an independent predictor of mortality in patients with angina pectoris.
Procedures
Coronary angiography
Selective coronary angiography is the definitive diagnostic test for evaluating the anatomic extent and severity of coronary artery disease.
Consider coronary angiography in symptomatic patients with inconclusive noninvasive study results, in survivors of sudden cardiac death, in those who are considered to have a poor prognosis based on the results of noninvasive studies, in those with occupational requirements for a definite diagnosis (eg, pilots), or in patients with coronary artery disease who are severely symptomatic despite maximal medical therapy.
In patients in whom Prinzmetal angina is suggested, provocative testing with ergonovine maleate during coronary angiography may be useful.
Intra-aortic balloon counterpulsation
Intra-aortic balloon counterpulsation can be used in patients who continue to have unstable angina pectoris despite maximal medical treatment. This procedure should be followed promptly by coronary angiography with possible coronary revascularization. [3]
Enhanced external counterpulsation
In patients whose angina is refractory to medical therapy who are not suitable candidates for either percutaneous or surgical revascularization, enhanced external counterpulsation (EECP) is a safe and noninvasive alternative therapy. [4, 24] It increases coronary perfusion and reduces myocardial oxygen demand by diastolic augmentation of the central aortic pressure. Several studies have shown that patients treated with enhanced external counterpulsation have a significantly reduced number of anginal episodes, improved exercise tolerance, and decreased daily use of nitroglycerin tablets. Its therapeutic effects on quality of life are noted to remain at 1-year follow-up. [25, 26]
EECP also improves systolic blood pressure in patients with refractory angina. In a recent study of 108 consecutive patients undergoing EECP, on average, EECP decreased systolic blood pressure during treatment and follow-up; but in patients with low baseline systolic blood pressure (< 110 mm Hg), EECP significantly increased systolic blood pressure. [4]
Staging
The Canadian Cardiovascular Society grading scale is used for classification of angina severity, as follows:
-
Class I - Angina only during strenuous or prolonged physical activity
-
Class II - Slight limitation, with angina only during vigorous physical activity
-
Class III - Symptoms with everyday living activities, ie, moderate limitation
-
Class IV - Inability to perform any activity without angina or angina at rest, ie, severe limitation
The New York Heart Association classification is also used to quantify the functional limitation imposed by patients' symptoms, as follows:
-
Class I - No limitation of physical activity (Ordinary physical activity does not cause symptoms.)
-
Class II - Slight limitation of physical activity (Ordinary physical activity does cause symptoms.)
-
Class III - Moderate limitation of activity (Patient is comfortable at rest, but less than ordinary activities cause symptoms.)
-
Class IV - Unable to perform any physical activity without discomfort, therefore severe limitation (Patient may be symptomatic even at rest.)
Unstable angina is defined as new-onset angina (ie, within 2 mo of initial presentation) of at least class III severity, significant recent increase in frequency and severity of angina, or angina at rest.
