Prognostic significance of the invasive assessment of coronary microvascular dysfunction: a systematic review and meta-analysis

Abstract Background Although obstructive epicardial coronary artery disease has been considered a prerequisite for myocardial ischemia, recent advancements in the understanding and diagnosis of coronary microvascular dysfunction (CMD) indicate that microvascular disease also affects myocardial perfusion and can provoke ischemia, even in the absence of significant epicardial stenoses. Considering the effect of CMD in the myocardium, its presence could result in an elevated risk for mortality as well as major adverse cardiovascular events (MACE). Purpose Thus, we performed a systematic review and meta-analysis aiming to evaluate the prognostic value of invasive markers of CMD in mortality and MACE. Methods We performed a systematic search in 3 different databases (MEDLINE/PubMed, Web of Science and Scopus). After selecting all appropriate studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a random effect meta-analysis was performed. Results A total of 40 studies and 16,832 patients (mean age: 55.5 ± 10.6 years; 65% male) were included, with a mean follow-up of 37 months. Among included patients, 34.9% had abnormal values of CFR (2.5)and/or IMR (25), indicating CMD, while 65.1% had normal CFR/IMR. The presence of CMD, in comparison to normal individuals, was associated with a significantly increased risk for all-cause Risk Ratio (RR): 2.03; 95% Confidence Interval (CI): 1.62-2.54 and cardiovascular morality (RR: 2.61; 95%CI: 2.06-3.31). Moreover, patients with a CMD diagnosis had significantly increased major adverse cardiovascular event rates (RR: 2.65; 95%CI: 2.31-3.04). In specific, the diagnosis of CMD significantly increased the rates of myocardial infarction (RR: 2.17; 95%CI: 1.56-3.02), hospitalization for heart failure (RR: 2.68; 95%CI: 1.73-4.16) and future revascularization (RR: 1.97; 95%CI: 1.64-2.36), while no difference was noted in respect to stroke events (RR: 1.58; 95%CI: 0.89-2.80). Conclusion This systematic review and meta-analysis shows that the presence of CMD, as diagnosed with invasive coronary physiology markers, is significantly associated with increased all-cause and cardiovascular mortality, as well as major adverse cardiovascular events. Therefore, proper evaluation of the coronary microcirculation is essential, in order to identify patients at risk and timely provide therapeutic interventions.