Silent ischemia represents an underappreciated manifestation of coronary artery disease (CAD), occurring in up to 20% to 40% of patients with stable and unstable coronary syndromes. It is estimated that 195,000 silent first myocardial infarctions (MIs) occur each year, which assumes that 21% of MIs are silent. By definition, patients are asymptomatic, lacking typical or atypical anginal symptoms. Silent ischemia may be documented by a variety of diagnostic modalities, including resting electrocardiogram (ECG), ambulatory ECG (AECG), nuclear scintigraphy, and echocardiography.

Patients may be loosely categorized into three groups, collectively representing a continuum of silent ischemia.

A. Type I have asymptomatic ischemia with no known CAD history with asymptomatic MI patterns. Clinicians may discover evidence of subclinical MI from a resting ECG or a preoperative stress test. In the Framingham study, 12.5% of patients with MI had an unrecognized “silent” infarction. Patients may also present with arrhythmias or sudden death from subsequent scar. These patients are considered to have an ineffective “anginal warning system.”

In addition, a subset of this group includes patients with asymptomatic ischemia without a history of infarction. Silent ischemia is often discovered by stress tests after referral for aggressive primary screening. This type of screening may occur in patients with diabetes, strong family histories, or a high-risk electron beam computed tomography (EBCT) result. Given the increasingly technological nature of medical culture, the prevalence of these patients is likely to rise. AECG is rarely used as a primary screening modality. The American College of Cardiology and American Heart Association (ACC/AHA) guidelines consider the use of AECG for ischemia monitoring in asymptomatic individuals as a class III recommendation.

B. Type II have symptomatic MIs but subsequent asymptomatic ischemic syndromes. Ischemia is often missed because of a lack of symptoms. Patients in this category are most often encountered after a positive stress test or the rarely ordered AECG. Type II patients may have an abnormal pain threshold.

C. Type III encompass the largest patient population with silent ischemia. These patients with known CAD have both symptomatic and asymptomatic ischemia. Between 20% and 40% of patients with chronic anginal symptoms have silent ischemia. About 75% of ischemic episodes are silent and only 25% are symptomatic.

Most patients with silent ischemia are either never identified or identified retrospectively. In the Asymptomatic Cardiac Ischemic Pilot (ACIP) study, patients with frequent silent ischemic events were found to be at increased risk for advanced
coronary disease, including high-risk coronary anatomy such as three-vessel disease. Currently, testing to detect ischemia in asymptomatic patients is controversial. The ACC/AHA guidelines consider the use of exercise ECG testing (without imaging) in asymptomatic patients with possible myocardial ischemia on AECG or severe coronary calcification on EBCT as a class IIb recommendation. The use of exercise plus imaging stress testing (echo and nuclear) in asymptomatic patients with a low-risk Duke treadmill score on exercise ECG testing is a class III recommendation. In patients with an intermediate- or high-risk Duke treadmill score, it is a class IIb recommendation. In asymptomatic patients with prior revascularization with high-risk features, periodic stress testing is a class IIb recommendation.

A. The exact explanation for a lack of symptoms in the face of unequivocal ischemia remains unknown. It likely represents abnormal modulation of cardiac pain perception at different levels in the afferent pathway of the heart.

B. The association between diabetes and silent ischemia and painless infarction has been attributed to autonomic neuropathy. A higher threshold for pain has been related to increased baseline plasma β-endorphin levels and increased age. A potential connection exists between baroreceptor function and pain perception. This may explain the relationships among increased systolic blood pressure, reduced sensitivity to ischemic pain, and the demonstration of anginal relief with carotid sinus stimulation. Results of one study suggested that the gating of afferent signals at the thalamic level is a potential mechanism for silent ischemia. Patients with symptoms had activation of basal frontal, anterior, and ventral cingulate cortices and the left temporal pole. Cortical activation was limited to the right frontal region in patients with silent ischemia. It also has been proposed that, among type III patients, asymptomatic ischemia may represent shorter and less severe episodes compared with symptomatic episodes.

A. Medications effective in preventing symptomatic ischemia (i.e., nitrates, calcium antagonists, and β-blockers) and in decreasing myocardial O₂ demand are also effective in reducing or eliminating episodes of silent ischemia. In one randomized study, metoprolol was found to be better than diltiazem in reducing the mean number and duration of ischemic episodes. However, the combination of calcium antagonists and β-blockers was more effective than either agent alone. Lipid-lowering therapy has also shown a reduction of ischemia on AECG. The ACC/AHA guidelines currently regard the use of ASA (aspirin), β-blockers, angiotensin-converting enzyme inhibitors, and statins as class I recommendations in asymptomatic patients with evidence of previous MI and class IIa recommendations in patients without history of previous MI. It has also been postulated that ranolazine may also reduce ischemia before symptoms become present.

B. The goal of therapy remains controversial. It is not clear whether therapy should be guided by ischemia or angina. The ACIP study revealed no difference in benefit from either of these approaches. However, 2-year follow-up data from this study demonstrated improved prognosis with initial revascularization compared with angina- or ischemia-guided medical therapy. The Swiss Interventional Study on Silent Ischemia type I (SWISSI I) randomized 54 type I subset patients to treatment with antianginal medications and aspirin versus risk factor modification only. Their findings showed that treatment with the combination of antianginal drug therapy and aspirin appeared to significantly reduce cardiac events, including cardiac death, nonfatal MI, or acute coronary syndrome. In addition, these patients had consistently lower rates of exercise-induced ischemia during follow-up. The SWISSI II study randomized 201 patients with type II silent ischemia to percutaneous coronary intervention (PCI) versus ongoing anti-ischemic medical therapy. The results showed a significant decrease in rates of cardiac death, nonfatal MI, and subsequent
need for revascularization in patients in the PCI group over a 10-year follow-up period. Similarly, in patients with type I silent ischemia, with an ineffective “anginal warning system,” it has been suggested that it may be reasonable to treat silent ischemia in a manner equivalent to that for symptomatic ischemia in the general population in terms of revascularization and medical therapy.