Mechanisms of Coronary Microcirculatory Dysfunction in Patients With Aortic Stenosis and Angiographically Normal Coronary Arteries

Abstract

Background-Development of left ventricular hypertrophy in aortic stenosis (AS) is accompanied by coronary microcirculatory dysfunction, demonstrated by an impaired coronary vasodilator reserve (CVR). However, evidence for regional abnormalities in myocardial blood flow (MBF) and the potential mechanisms is limited. The aims of this study were to quantitatively demonstrate differences in subendocardial and subepicardial microcirculation and to investigate the relative contribution of myocyte hypertrophy, hemodynamic load, severity of AS, and coronary perfusion to impairment in microcirculatory function. Methods and Results-Twenty patients with isolated moderate to severe AS were studied using echocardiography to assess severity of AS, cardiovascular magnetic resonance to measure left ventricular mass (LVM), and PET to quantify resting and hyperemic (dipyridamole 0.56 mg/kg) MBF and CVR in both the subendocardium and subepicardium. In the patients with most severe AS (nϭ15), the subendocardial to subepicardial MBF ratio decreased from 1.14Ϯ0.17 at rest to 0.92Ϯ0.17 during hyperemia (PϽ0.005), and subendocardial CVR (1.43Ϯ0.33) was lower than subepicardial CVR (1.78Ϯ0.35; Pϭ0.01). Resting total LV blood flow was linearly related to LVM, whereas CVR was not. Increase of total LV blood flow during hyperemia (mean value, 89.6Ϯ59.6%; range, 17% to 233%) was linearly related to aortic valve area. The decrease in CVR was related to severity of AS, increase in hemodynamic load, and reduction in diastolic perfusion time, particularly in the subendocardium. Conclusions-CVR was more severely impaired in the subendocardium in patients with LVH attributable to severe AS.Severity of impairment was related to aortic valve area, hemodynamic load imposed, and diastolic perfusion rather than to LVM. (Circulation. 2002;105:470-476.)

Functional Changes in Coronary Microcirculation After Valve Replacement in Patients With Aortic Stenosis

“…2 Contiguous 10-mm SA slices were acquired during a single breath-hold using a segmented gradient-echo Turbo-FLASH sequence, and LVM was calculated. 13 LVM was divided by body surface area to give LVM index (LVMI).…”

“…15 The sinograms obtained were corrected, reconstructed, and rebinned into 2D sinograms, and factor images were generated as described previously. 2 The factor images were resliced into short-axis images in an orientation perpendicular to the long axis of the left ventricle. Regions of interest were defined on these images corresponding to septal, anterior, lateral, and posterior walls of the left ventricle in the apical, mid, and basal planes.…”

“…4 We have demonstrated that functional vascular compressive forces produced by an increase in LV filling pressure (extravascular resistance) and reduction in hyperemic diastolic perfusion limit MBF in those patients with AS. 2 It is hypothesized that increased extravascular resistance leads to deformation of vessels in the myocardial microvasculature by the mechanical motion of the beating heart and reduction in diastolic perfusion is responsible for myocardial ischemia in the absence of epicardial coronary artery stenosis, particularly in the subendocardium. Normal CVR can be restored in renovascular hypertensive rats by reversal of LVH.…”

“…evelopment of left ventricular hypertrophy (LVH) in patients with aortic valve stenosis (AS) is associated with abnormalities in microcirculatory function, as demonstrated by a reduced coronary vasodilator reserve (CVR), 1,2 and this may explain anginal symptoms despite angiographically normal coronary arteries. 3 Perimyocytic fibrosis 4 and reduction in the number of resistance vessels per unit weight 5 may contribute to the reduction in CVR in LVH secondary to hypertension and hypertrophic cardiomyopathy.…”

“…3 Perimyocytic fibrosis 4 and reduction in the number of resistance vessels per unit weight 5 may contribute to the reduction in CVR in LVH secondary to hypertension and hypertrophic cardiomyopathy. However, recent work suggests that increased systolic impedance to coronary flow as a result of perivascular compression 6 and, most importantly, a reduction in diastolic perfusion 2 are the primary contributors to impairment of coronary microcirculatory function in AS, predominantly because of curtailment in maximal myocardial blood flow (MBF).…”