Microvascular resistance reserve and cardiovascular outcomes: the FLOW-CMD registry

BACKGROUND AND AIMS: Microvascular resistance reserve (MRR) is a novel index for assessing coronary microvascular function that is independent of epicardial coronary artery stenosis and subtended myocardial mass. However, limited data are available regarding the clinical relevance of coronary microvascular dysfunction, defined by MRR in patients undergoing clinically indicated invasive coronary angiography. This study sought to evaluate the incidence and prognostic impact of coronary microvascular dysfunction defined by MRR in routine practice. METHODS: In the prospective, multicentre FLOW-CMD Registry, 1003 consecutive patients with suspected ischaemic heart disease who underwent clinically indicated invasive coronary angiography with comprehensive coronary physiologic assessment were prospectively enrolled. Coronary microvascular dysfunction was defined as MRR ≤2.5 in any evaluated vessel. The primary endpoint was a composite of all-cause death, myocardial infarction, clinically-driven repeat revascularisation, or hospitalisation for heart failure. RESULTS: Coronary microvascular dysfunction was identified in 334 of 1003 patients (33.3%). MRR as a continuous variable was associated with the risk of the primary endpoint (hazard ratio [HR] per 1-unit decrease, 1.16; 95% confidence interval [CI] 1.03-1.32; P=0.026). At a median follow-up of 1.9 years, the primary endpoint occurred in 47 of 334 patients (18.2%) with coronary microvascular dysfunction and 49 of 669 patients (8.6%) with preserved microvascular function (HR 1.94; 95% CI 1.30-2.90; P=0.001). On multivariable analysis, coronary microvascular dysfunction defined by MRR ≤2.5 was independently associated with the primary endpoint (adjusted HR 1.78; 95% CI 1.06-2.99; P=0.030). CONCLUSIONS: In patients with suspected ischaemic heart disease undergoing invasive coronary angiography, coronary microvascular dysfunction defined by MRR ≤2.5 was observed among one-third of patients, and was associated with an increased risk of a composite of all-cause death, myocardial infarction, clinically-driven repeat revascularisation, or hospitalisation for heart failure (Multicenter FLOW-CMD Registry ClinicalTrials.gov number, NCT05369182).