Detection of silent myocardial ischemia: Is it clinically relevant?

Abstract

Silent myocardial ischemia is defined as objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. The first description of silent ischemia date to the 1970s, but despite intensive investigation, its pathophysiology, detection, prevalence, and clinical significance are still debated. The need and the benefit of treating silent ischemia, particularly in patients without history of coronary artery disease (CAD) and who are asymptomatic, remain questionable. Asymptomatic (silent) myocardial ischemia may be identified during routine daily activities or during stress testing in patients without or with known CAD. One of the earliest investigations addressing the prevalence and significance of silent myocardial ischemia in asymptomatic subjects is the United States Air Force study, conducted in 1,390 men, 111 of whom had positive exercise tests. Thirty-four of these 111 (about 2.5% of the total) had coronary artery lesions of at least 50% stenosis. Thaulow et al studied 2014 Norwegian male office workers between 40 and 59 years of age (mean age 50 year). Coronary angiography in men with positive exercise tests demonstrated that 69 had stenoses of 50% or greater in one coronary artery; 50 of these (2.7% of the total) patients were completely asymptomatic, a percentage similar to that found in the United States Air Force study. He et al reported in nearly 4,000 subjects studied, that the severity of coronary artery calcification by electron-beam computed tomography (CT) can predict silent myocardial ischemia on stress single-photon emission computed tomography (MPS). Silent myocardial ischemia was present in 2.6% of patients with coronary calcium score between 11 and 100, 11.3% of patients with scores between 101 and 399, and 46% of patients with scores above 400. In this issue of the Journal, Malhotra et al evaluated the relationship between silent myocardial ischemia and CAD risk factors in a retrospective analysis of 1,354 asymptomatic patients without known CAD referred for stress MPS. The most common reasons for referral of these patients without chest pain or dyspnea were CAD risk factors, atrial fibrillation, and pre-operative evaluation. As expected, the prevalence of silent myocardial ischemia in these asymptomatic subjects was very low (7.2%). The authors identified a positive relationship between the number of CAD risk factors and the prevalence of silent myocardial ischemia. However in older patients ([74 years), who had a significantly greater prevalence of silent ischemia, the presence and number of risk factors were not predictive. The positive predictive value of an abnormal MPS for predicting angiographic CAD was only 53% and, among all asymptomatic patients referred for stress MPS, significant anatomical CAD was found in only 31 of 1,354 (2%) patients. Malhotra et al concluded that their findings support current guidelines, which generally advocate against routine testing in asymptomatic patients. Unfortunately, they did not provide outcome information for these patients, in particular for the 60 patients (4.4% of overall study population) defined to have ‘‘prognostically significant ischemia’’ (i.e., [10% of left ventricular myocardium). Previous studies have found that silent myocardial ischemia detected in healthy individuals without known CAD has been shown to predict adverse events. The Lipid Research Clinic’s Coronary Primary Prevention Trial (LRCPPT) and the Multiple Risk Factor Intervention Trial (MRFIT) showed that the presence of asymptomatic myocardial ischemia detected during baseline treadmill exercise testing in subjects without known CAD predicted a more than fivefold increased risk of coronary events and cardiac death during the 7to 10-year follow-up period. Other studies evaluated From the Department of Translational Medical Sciences, University Federico II, Institute of Diagnostic and Nuclear Development, SDN Foundation; and Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy. Reprint requests: Alberto Cuocolo, MD, Department of Advanced Biomedical Sciences, University Federico II, Via Pansini 5, 80131 Naples, Italy; cuocolo@unina.it. J Nucl Cardiol 2013;20:707–10. 1071-3581/$34.00 Copyright 2013 American Society of Nuclear Cardiology. doi:10.1007/s12350-013-9725-z