Prognostic implications of microvascular resistance reserve in symptomatic patients with intermediate coronary stenosis

Abstract Background Microvascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). Objective To evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. Methods The current study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiologic assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR)≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR≤3.0. Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. Results Among the total patients, 172 patients (31.4%) had FFR≤0.80 and 200 patients (36.6%) had CMD defined by MRR≤3.0. MRR showed no significant correlation with FFR (R=-0.031, P=0.469), however, it was significantly correlated with index of microcirculatory resistance (R=-0.353, P<0.001), NT-proBNP (R=-0.296, P<0.001), left ventricular filling pressure (E/e’) (R=-0.224, P<0.001), and diastolic dysfunction grade (P<0.001). During median follow-up of 3.3 years (interquartile range from 2.0 to 4.5 years), MRR was significantly associated with MACE risk (HR 1.23 per-1 decrease, 95% CI 1.12-1.36, P<0.001). CMD defined by MRR≤3.0 was associated with an increased MACE risk in both FFR>0.80 (41.0% vs. 26.0%; HRadj 1.59, 95% CI 1.07-2.35, P=0.021) and FFR≤0.80 (34.7% vs. 14.8%; HRadj 2.32, 95% CI 1.12-4.82, P=0.024) groups. Conclusion Decreased MRR was associated with the presence of cardiac diastolic dysfunction as well as with increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk of a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis.