Coronary Flow Reserve Predicts Cardiopulmonary Fitness in Patients with Coronary Artery Disease Independently of Systolic and Diastolic Function

AIMS: Despite revascularization and optimal medical treatment, patients with coronary artery disease (CAD) have reduced exercise capacity. In the absence of coronary artery stenosis, coronary flow reserve (CFR) is a measure of coronary microvascular function, and a marker of future poor outcome in CAD patients. The aim of this study was to examine the relationship among CFR, systolic and diastolic function, peripheral vascular function, and cardiopulmonary fitness in CAD patients. METHODS AND RESULTS: Forty patients with median left ventricular ejection fraction (LVEF) 49 (interquartile 46-55) with documented CAD without significant left anterior descending artery (LAD) stenosis underwent cardiorespiratory exercise test with measurement of VO2 peak, digital measurement of endothelial function and arterial stiffness, and an echocardiography with measurement of LVEF using the biplane Simpson model, mitral early (E) and late (A) inflow velocities, and tissue Doppler diastolic (e') and systolic (s') velocities. Peak coronary flow velocity (CFV) was measured in the LAD using pulse-wave Doppler. CFR was calculated as the ratio between peak CFV at rest and during vasodilator stress. Median CFR was 2.22 (1.90-2.62) and VO2 peak was 21.8 (17.6-25.5). VO2 peak correlated significantly with CFR (r = 0.57, P < 0.001), E/e' (r = -0.35, P = 0.04), and s' (r = 0.41, P = 0.01) and with LVEF (r = 0.35, P = 0.03). CFR remained independently associated with VO2 peak after adjustment for systolic and diastolic function. CONCLUSIONS: Coronary flow reserve measured noninvasively predicts cardiopulmonary fitness independently of resting systolic and diastolic function in CAD patients, indicating that cardiac output during maximal exercise is dependent on the ability of the coronary circulation to adapt to the higher metabolic demands of the myocardium.