Abstract

Background: Coronary vasomotor dysfunction identifies patients at risk for cardiac death. We sought to determine the association between global coronary flow reserve (CFR, an integrated measure of coronary vasomotor function) and adverse cardiovascular events, in patients referred for coronary angiography with or without subsequent revascularization. Methods and Results: Consecutive patients (n=329) without prior coronary artery bypass surgery (CABG), heart failure, or left ventricular (LV) systolic dysfunction referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography (PET) were followed (median 3.1 years) for cardiovascular death and heart failure admission. Extent and severity of coronary angiographic stenosis was estimated using the CAD prognostic index (CADPI) and CFR measured noninvasively by PET. A subset of patients (n=193) underwent early revascularization, defined as CABG and/or percutaneous coronary intervention (PCI) within 90 days after PET. After adjusting for clinical risk score, LV ejection fraction, LV ischemia, CADPI, and time-dependent early revascularization with CABG and/or PCI, CFR remained independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95% CI 1.20-3.40, p=0.008). In adjusted analysis, there was a significant interaction (p=0.04) between CFR and early revascularization by CABG, such that patients with impaired CFR who underwent CABG (n=39), but not PCI (n=154), experienced event rates comparable to those with preserved CFR, independently of revascularization. Conclusions: CFR associated with adverse cardiovascular outcomes independently of angiographic severity, and modified the effect of early revascularization. Diffuse atherosclerosis and microvascular dysfunction may contribute to the pathophysiology of cardiovascular death and heart failure, and impact upon the outcomes of revascularization.

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