Coronary Microvascular Dysfunction in Patients with Cardiomyopathies

Abstract

A nginal symptoms and electrocardiographic changes suggestive of myocardial ischemia, despite angiographically normal coronary arteries, are common in patients with cardiomyopathies and those with left ventricular hypertrophy secondary to pressure overload. Studies using positronemission tomography (PET) to measure regional myocardial blood flow have demonstrated that maximum myocardial blood flow and coronary flow reserve are severely blunted in patients with hypertrophic as well as dilated cardiomyopathy. 1,2 In the absence of epicardial stenoses, blunted maximum myocardial blood flow and coronary flow reserve are suggestive of coronary microvascular dysfunction. 3,4 Furthermore, it has been demonstrated that in both hypertrophic and dilated cardiomyopathy, the severity of coronary microvascular dysfunction, assessed by measuring myocardial blood flow with PET, is an independent predictor of prognosis. 2,5 In patients with cardiomyopathies, coronary microvascular dysfunction can be sustained by a number of different pathogenetic mechanisms. These include structural and functional abnormalities of the intramural arterioles as well as extravascular mechanisms (eg, increased extramural compression). 4 Article see p 161Anderson-Fabry disease (AFD) is an X-linked deficiency of lysosomal ␣-galactosidase A. 6 This deficiency results in multiorgan damage from glycosphingolipid deposition, leading to renal, cardiac, and cerebrovascular disease and premature death. Patients with AFD complain of angina despite angiographically normal coronary arteries. Recent studies have also shown that there is progressive deterioration in left ventricular systolic function and myocardial scarring in patients with AFD cardiomyopathy. A number of mechanisms may contribute to microvascular dysfunction in these patients. AFD cardiomyopathy is characterized by globotriaosyl-ceramide (Gb 3 ) and related glycosphingolipid deposition in myocytes, conduction tissue, vascular endothelium, and valvular tissue. This is accompanied by secondary changes, such as myocyte hypertrophy and fibrosis, often mimicking hypertrophic cardiomyopathy. 7 In the vasculature, Gb 3 accumulates in endothelial and smooth muscle cells, possibly causing structural abnormalities that may be responsible for vascular dysfunction. In addition, it has been demonstrated that patients with AFD have increased intimamedia thickness in the carotid and brachial arteries and abdominal aorta. These structural changes are accompanied by evidence of abnormal flow-mediated vasodilatation in the brachial artery compared with healthy controls. 8 In a recent study, Elliott et al 9 used PET to measure regional myocardial blood flow at baseline and during adenosine hyperemia in patients with AFD with angiographically normal coronary arteries. The results of this study showed that both resting (0.99Ϯ0.17 versus 1.17Ϯ0.25 mL/g per minute; PϽ0.05) and hyperemic (1.37Ϯ0.32 versus 3.44Ϯ0.78 mL/g per minute; PϽ0.0001) myocardial blood flow were severely blunted in patients with AFD compared wit...

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