Review
Reviewing myocardial silent ischemia: Specific patient subgroups

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Abstract

Silent myocardial ischemia (SMI) is a relatively common, yet poorly understood, clinical entity. The most accurate means of detecting SMI and the precise treatment endpoints remain unclear. However, the presence of SMI correlates with the likelihood of future adverse cardiac events. Evidence suggests that patients at high risk of severe cardiac ischemia, even with the absence of symptoms, derive the greatest benefit from an aggressive diagnostic and therapeutic approach. This paper is giving a detailed review of SMI in regards to specific patient subgroups, i.e. populations with diabetes mellitus, hypertension, elderly patients, post-revascularization patients, women, the suggested screening procedures for each subgroup, as well as the emersion of new markers for the selection of high-risk patients for screening.

Introduction

From the 1980s, Cohn classified silent myocardial ischemia (SMI) into 3 groups. Type I patients are those who are totally asymptomatic and have no previous history of angina pectoris or myocardial infarction. Type II patients are survivors of acute myocardial infarction, who have evidence of inducible, but asymptomatic, ischemia, usually on exercise testing. Type III patients are those with angina, who also have episodic silent ischemia. The last two groups consist of patients with known coronary artery disease (CAD) [1].

However, the number of studies performed during the past two decades, concerning SMI, its prevalence, prognosis, risk factors and routine screening in large populations, has established the need to investigate SMI in specific patient subgroups, and more precisely diabetic, hypertensive and elderly patients, since SMI increases the risk of future adverse cardiac events and therefore the quality of life, making its early detection even more important.

A review of the literature shows prevalence rates of SMI ranging from 9 to 57% [2], [3]. This broad range is probably due to differences in the population studied (e.g. age of patients, duration of underlying disease, inclusion or exclusion of patients with high-risk factors or symptoms of CAD, and definition of SMI). The great variety of the screening techniques used (e.g. resting electrocardiography, exercise testing, stress ultrasound, scintigraphy, or coronary angiography), as well as the number of positive screening tests required to access SMI, are equally responsible for the wide range of prevalence rates of SMI.

Special reference should be made in the role of sex in CAD. Men have a higher incidence of SMI compared to pre-menopausal women, but this, changes quickly in post-menopausal women. This is mainly due to the risk factors typically associated with CAD. Lipids in women are only weakly associated with CAD [4], while the prevalence of hypertension greatly increases with age, so nearly 80% of women older than the age of 75 are hypertensive [5].

Although the prognostic implication of abnormal electrocardiographic (ECG) monitoring in asymptomatic patients has been evaluated [6], the lack of consistent data to support this technique as an independent predictor of future cardiac events makes the functional or pharmacological stress test the preferred method for the detection of silent ischemia [7]. If the decision is made to perform a stress test in an asymptomatic patient to assess the degree of detectable myocardial ischemia, then an exercise test is preferable to a pharmacological test, as it depicts the heart's actual workload and simulates better everyday cardiac strain. Additional prognostic information includes total exercise time, blood pressure, heart rate response during exercise and ST-segment abnormalities [8].

Concerning patients with known CAD, ambulatory ECG monitoring provides a unique insight into the presence and severity of myocardial ischemia. Ambulatory ECG is generally performed in two clinical settings to assess ischemic risk: as outpatient evaluation of stable CAD patients and as inpatient evaluation of patients with an acute coronary syndrome who need more prolonged recordings [9]. Meanwhile, a strong consideration should be given to the addition of echocardiographic or nuclear imaging studies on patients with baseline ECG abnormalities (Pre-excitation syndrome — Wolf Parkinson White, > 1 mm of resting ST depression, complete left bundle branch block), patients taking digoxin, women, and those who have undergone prior coronary revascularization procedures. In patients who are unable to exercise, non-invasive techniques include nuclear imaging or echocardiography with pharmacologic provocation. More precisely, pharmacological stress echo typically relies on an incremental infusion protocol of dobutamine in doses of 10, 20, 30, and 40 μg/kg/min, augmented by atropine to obtain an adequate heart rate. An alternative to dobutamine is dypiridamole infusion, which relies on provoking ischemia, by differential vasodilation in normal and stenotic arteries [10].

Section snippets

SMI and diabetes mellitus

CAD, the major cause of morbidity and mortality in diabetes mellitus, is the leading chronic macrovascular complication of diabetes mellitus due to atherosclerosis. Not only is the risk of CAD increased in diabetic patients compared to the normal population, but also the prognosis of CAD is far more severe in diabetics than in non-diabetics, while the course of myocardial infarction is more severe with a higher rate of mortality in diabetic patients [11].

SMI and silent coronary stenoses are two

Clinical implications and future directions

Clearly, it is neither advisable nor feasible to screen every middle-aged individual for myocardial ischemia. Rather, it is prudent to only recommend the treadmill test for high-risk healthy individuals, so as to avoid unnecessary testing in low-risk subjects, but also to reduce the risk of false-positive findings. The next question is obviously what to do for those with evidence of SMI during exercise testing. It is generally recommended that the presence of SMI, detected by ECG changes during

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