Susan Sanner
Cardiac Diagnostic Testing
Noninvasive Assessment of Coronary Artery Disease
Since the advent of coronary artery disease (CAD) as a diagnosis, numerous ways for the proper assessment of this illness noninvasively have flourished. Although each test has its advantages, each also has limitations (Table 116-1). The optimum assessment of CAD is a thorough history and physical examination that includes prior medical history of myocardial infarction or CAD and the patient’s present complaint (e.g., angina, radiating pain, tingling, or numbness) in conjunction with ascertaining the family history of CAD. In addition, immediate electrocardiographic (ECG) and laboratory biomarker testing should be considered to ensure a proper diagnosis and an adequate interventional plan.1 (Cardiac catheterization is indicated if ECG findings and biomarkers indicate an acute myocardial infarction.) This chapter addresses the evaluation of suspected CAD in the absence of acute infarction.
TABLE 116-1
Exercise Testing Comparisons
| Test | Benefits and Indications | Limitations |
| Treadmill exercise | Assesses ischemia, functional capacity, prognosis Equipment widely available Accuracy established in different populations | Lower sensitivity than other tests listed Poor specificity with women, resting ECG ST-T abnormalities, LVH does not indicate site or extent of infarct |
| Exercise myocardial perfusion imaging | Reproducible results Improved sensitivity and specificity higher diagnostic accuracy | Increases costs over treadmill testing Requires longer than treadmill exercise alone Modest radiation exposure Artifacts from soft tissue (breast) or in obese patients attenuate signal, decrease specificity |
| Cardiac magnetic resonance imaging (MRI) | High resolution of cardiac structure, function, and morphology No radiation exposure Stress perfusion MRI an option Can be used with most cardiac stents | Use in claustrophobic patients can be difficult because of patient ability to stay in MRI machine contraindicated in patients with implantable ferromagnetic objects (debrillators) |
| Exercise radionuclide angiography | Well validated to identify patients with severe disease Risk stratification after MI Good images with obese patients or those with COPD Accurate information about ejection fractions | Limited availability and high expense Uses bicycle, not treadmill exercise Inaccurate when heart rate is irregular Reduced specificity with women, abnormal resting left ventricular function |
| Exercise echocardiography | Shorter test time, lower cost than nuclear imaging Assesses multiple parameters: global and regional ventricular function, chamber size, wall thickness, valve function Used with resting ECG abnormalities, LBBB Detects reversible ischemia (wall motion abnormalities develop with stress) | Images limited with obesity or obstructive lung disease Does not detect non–blood flow limiting blockages Reduced accuracy with resting wall motion abnormalities (prior MI, paced rhythm, certain types of cardiac surgeries) |
| Pharmacologic stress with dipyridamole or adenosine | Accurate assessments in patients unable to complete exercise protocol Useful assessment in patients with claudication or musculoskeletal limitations Side effects rapidly reversible by ending infusion or administering aminophylline | Cannot assess functional capacity Contraindicated with hypotension, sick sinus syndrome, high-grade heart block, hyperreactive airways, caffeine or theophylline dependence, oral dipyridamole therapy Chest pain during test not indicative of CAD |
| Dobutamine echocardiography | Improves CAD assessments in patients unable to exercise Side effects rapidly reversible by terminating infusion or administering a beta blocker) Perfusion defects represent true myocardial ischemia | Cannot assess functional capacity Contraindicated with recent MI (<1 week), unstable angina, high-grade heart block, BBB, severe aortic stenosis, hypertrophic obstructive cardiomyopathy, supraventricular dysrhythmias, ventricular tachycardia (history or current), uncontrolled hypertension, large aneurysm, severe pulmonary hypertension, beta blocker dependence |
Once all the results of the initial laboratory and ECG testing are reviewed, a pretest probability of disease can be generated and additional tests can be ordered.2 The probability of CAD can be calculated by considering the chosen noninvasive test’s sensitivity and specificity.2 Selection of the proper cardiac test (see Table 116-1) for an individual depends on the person’s risk stratification, age, and tolerable level of activity. The most common and least invasive test for diagnosis of CAD is the stress test, also called the exercise tolerance test (ETT) or treadmill exercise.
Pathophysiology of Coronary Artery Disease
CAD exists when coronary arteries are narrowed by atherosclerotic plaque formation, plaque rupture, or spasm. This narrowing impedes coronary blood flow, resulting in hypoperfusion of the myocardium. The hypoperfusion produces first diastolic, and then systolic dysfunction, with characteristic signs and symptoms, including chest pain. Typical ECG changes of ischemia result, although the ST-segment and T-wave changes that are central to demonstration of ischemia occur relatively late in the ischemic cascade.
Role of Inflammation and Atherogenesis
Inflammation has been implicated as one of the major processes that mediate the acceleration and progression of CAD and its complications. Inflammatory pathways have been very closely linked with the early development of atherosclerotic disease with plaque formation in coronary arteries, producing CAD. Inflammation and plaque composition both have an impact on the occurrence of acute plaque rupture, a cause of acute myocardial infarction.
Relation to Cardiac Stress Testing
Unlike most other circulatory beds in the body, the coronary circulation allows maximum oxygen extraction from the blood when the body is at rest. In a stress test or ETT, patients are asked to perform incremental exercises that result in positive chronotropic (rate) and inotropic (strength of contraction) stimulation of the cardiovascular system, which in turn increases myocardial oxygen demand. Increases in oxygen demand obligate an increase in myocardial blood flow. The healthy coronary circulation can increase flow approximately five times above the baseline level. The fundamental pathophysiologic change in CAD is a limitation of the ability of the coronary arterial circulation to vasodilate appropriately. As a result, the ability to increase coronary blood flow in the face of increased myocardial oxygen demand is limited, leading to an imbalance between oxygen supply and demand and resulting in myocardial ischemia.
Overview of Cardiac Diagnostic Testing
Noninvasive Tests and Biomarkers for Coronary Artery Disease
There is accumulating evidence that supports the use of noninvasive markers for the diagnosis of subclinical CAD. C-reactive protein, interleukin-6, and monocyte-macrophage colony-stimulating factor are markers that have shown promising results with their predictive value for future adverse cardiovascular events. A growing number of research studies have consistently suggested that either injury or insult to the vascular endothelium is a precursor for the process of atherogenesis to begin.3 These investigations have led to tests such as carotid intima-media thickness, augmentation index, flow-mediated dilation of the brachial artery, and pulse wave velocity; however, which of these noninvasive markers have a role in risk stratification for primary and secondary CAD prevention is under investigation.
Recent American College of Cardiology (ACC) guidelines give some guidance about noninvasive testing and markers for asymptomatic CAD based on an individual patient’s risk for CAD. ACC guidelines have as a Class 1 recommendation (suggested) based on Level B evidence (limited populations studied) that health care providers ascertain risk for cardiovascular disease in asymptomatic individuals by use of a global assessment such as the Framingham score.4 The ACC guidelines use the level of risk determined by these scores to evaluate the evidence and to classify recommendations for the use of various testing modalities in the investigation and determination of subclinical cardiovascular disease. For example, the ACC guidelines suggest that C-reactive protein can be used in asymptomatic men older than 50 years and women older than 60 years with low-density lipoprotein cholesterol below 160 mg/dL to determine if statin therapy is indicated and in asymptomatic intermediate-risk men older than 50 years and women older than 60 years to assess risk of cardiovascular disease.4 Ankle-brachial index assessment is acceptable for intermediate-risk individuals to determine their risk for subclinical cardiovascular disease.4
Recent evidence suggests that the Coronary Artery Calcium Score (CACS) may be beneficial for identifying CAD and is most likely to be useful in approaches for improving risk assessment in individuals who are at intermediate risk, although its role is not completely clear. The CACS is directly related to the plaque burden where zero constitutes a normal CACS; less than 10 is a low score and greater than 400 is a high score.5,6 Even with a designated score, evidence does not support targeted treatment of patients with high-risk CACS to improve outcomes.7 According to the American College of Cardiology Foundation (AACF)/American Heart Association (AHA) 2013 guidelines for assessment of cardiovascular risk, CACS may also be beneficial in asymptomatic adults with cardiovascular disease. Its primary advantage is that no patient preparation is required. However, owing to the issue of cost for a CACS determination, the exposure to radiation, and the unclear role of calcium scoring in low- to intermediate-risk patients with acute coronary syndrome, the ACC/AHA guidelines recommend CACS for individuals for whom, after having undergone a quantitative risk assessment, the treatment decision is unclear. CACS, in this case, may be able to help inform treatment.8
Overall, adequate risk assessment is the most challenging for individuals who are considered at low or intermediate risk for a cardiac event. Therefore the usefulness of inflammatory markers to predict a future cardiac event remains unclear and warrants further research.9,10
Exercise Tolerance Test
The standard first-line approach to initial testing for CAD is the ETT, during which the patient (attached to a 12-lead electrocardiogram) is continuously monitored during graded exercise. Multiple protocols are available for the ETT. The bicycle and treadmill are the two most often used. The primary goal of the ETT is to increase workload incrementally to induce ischemia or until a predetermined workload is reached. Multiple studies are available that have validated the efficacy and safety of ETT in patients with low risk of chest pain. Studies have also reported on the safety and efficacy of immediate exercise testing in low-risk patients who have normal ECG findings and biomarker levels and are not serially evaluated before stress testing.11 The ETT also provides data on the patient’s functional capacity, which has been shown to be a significant predictor of future cardiac events.11 In an ETT, patients are asked to perform incremental exercises based on standardized protocols. These result in positive chronotropic (rate) and inotropic (strength of contraction) response of the cardiovascular system, increasing myocardial oxygen demand. The normal hemodynamic response to these stimuli is an increase in absolute coronary blood flow. However, this ability is reduced in the presence of CAD, which leads to an imbalance between oxygen supply and demand, resulting in myocardial ischemia and ischemic changes in the electrocardiogram.
The ECG response of normal hearts is maintenance of an “isoelectric” ST segment during exercise and recovery. By standard criteria, a positive test result for CAD is defined by the development of horizontal or downsloping ST-segment depression of 1 mm measured 80 msec after the J point of the QRS complex (the junction between the QRS complex and the ST segment). ECG changes such as upsloping ST segment (elevation) or isolated T-wave downsloping (depression) have not demonstrated significant predictive value.
Because the interpretation of the test is based primarily on the development of characteristic ischemic ST-segment and T-wave changes, it is not surprising that resting ECG abnormalities can lead to a reduction in test sensitivity and specificity. The specificity of the routine ETT is reduced if the patient has had a prior myocardial infarction or if the patient has a resting bundle branch block conduction abnormality, paced rhythm, preexcitation syndromes, or inability to exercise because this produces persistent ST-segment and T-wave abnormalities.12
A number of other factors can interfere with the sensitivity of the exercise test in detecting CAD. Because an increase in coronary blood flow is related to an increasing heart rate and systolic blood pressure, clearly the sensitivity of the test is effort dependent. The standard is the peak heart rate achieved during exercise. Specifically, a test result is considered negative for CAD only if the patient exercises to at least 85% of the age-predicted maximum heart rate without evidence of inducible ischemia (maximum heart rate = [220 − age]). If the patient fails to achieve this “target” heart rate, the test should be considered nondiagnostic or insufficient to exclude ischemia. On the other hand, if there is evidence of ischemia (typical angina, ischemic ST changes) before the patient’s target heart rate is reached, the test is considered strongly predictive of significant CAD. A second important predictor of more advanced CAD is exercise-induced hypotension (i.e., a fall in systolic blood pressure of at least 20 mm Hg at any point during exercise). It is helpful to correlate the ischemic leads on exercise electrocardiography to the underlying coronary anatomy to roughly identify the culprit artery or arteries.
Medications such as beta blockers, digoxin, certain calcium channel blockers, and other antihypertensives can attenuate the heart rate, making the rest of the exercise test less diagnostic.13 The decision to discontinue beta blockers 1 or 2 days before testing is influenced by the purpose of the exercise test. For ETTs ordered to detect angina, it is recommended that the cardiologist be consulted about withholding the medication before the test is performed. ETTs performed to assess effectiveness of pharmacologic therapy require normal daily medication regimens. Imaging studies such as nuclear cardiac scanning may be useful in patients who undergo a stress test during beta blocker therapy.2
Another potential contributor to the ETT’s lack of sensitivity is derived from the limitations of the surface electrocardiogram related to the spatial distribution of the electrical abnormalities that occur in ischemia. This concept may be better understood if the electrocardiogram is considered an imaging tool that examines the electric forces of cardiac depolarization and repolarization. To detect ischemia, the repolarization phase of the cardiac cycle—the ST segment and T wave—is examined for abnormalities. ST-segment and T-wave changes in the surface electrocardiogram are related to both the extent and the severity of myocardial ischemia. As might be expected, the ETT is more sensitive for the detection of severe disease. Ischemia that is confined to the posterior or lateral segments of the left ventricle can be more difficult to detect.
When considering ETT, health care providers should be aware of its relative contraindications. For these patients, consultation with a cardiologist is recommended. Some pertinent contraindications to ETT include acute myocardial infarction, supraventricular ectopy, sustained ventricular arrhythmias, high-grade heart block, Wellens syndrome (highly correlated with CAD), hemodynamically significant aortic stenosis, severe hypertension, acute venous thromboembolic disease (deep venous thrombosis, pulmonary embolism), pericarditis, myocarditis, endocarditis, symptomatic congestive heart failure, and serious coexisting illness (such as diabetic ketoacidosis, pneumonia, or renal disease).13
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