Prognostic effect of invasively diagnosed coronary microvascular dysfunction: a systematic review and meta-analysis

The association of epicardial obstructive coronary artery disease with major adverse cardiovascular events (MACE) is established; however, accumulating evidence emphasizes the significant role of coronary microvascular dysfunction (CMD). The aim of this meta-analysis is to summarize the available evidence on the prognostic effect of CMD in cardiovascular outcomes and mortality.

Systematic literature search in MEDLINE/PubMed and Scopus was conducted to identify studies comparing the prognosis of CMD vs non-CMD using coronary flow reserve (CFR) and/or index of microcirculatory resistance (IMR) invasive indices. A meta-analysis to calculate pooled risk ratios (RR) was performed along with sensitivity and meta-regression analyses.

Thirty-one studies were included (n = 13,016, weighted mean age 58 years, males 57%, left ventricular ejection fraction 58%, CFR 2.6, IMR 24.4, CMD 33%). Meta-analysis of 24 studies (n = 8294) indicated a pooled RR for MACE of 2.55 (2.11, 3.10) for CMD vs non-CMD comparison. Consistent findings were observed for all-cause [1.88 (1.52, 2.33)] and cardiovascular mortality [2.76 (2.02, 3.76)], myocardial infarction [2.18 (1.56, 3.05)], revascularization [1.67 (1.06, 2.64)], heart failure hospitalization [3.46 (1.90, 6.30)], and stroke risk [1.85 (1.26, 2.71)]. The CFR and IMR-based analyses provided similar findings. Worse outcomes were observed in acute coronary syndrome patients and in those with the structural CMD endotype (abnormal CFR/abnormal IMR).

Invasively diagnosed CMD is associated with a 2.5-fold increase in MACE and a 3-fold increase in cardiovascular mortality. This finding highlights the importance of a more comprehensive assessment of coronary vasculature, including both the macro- and the microcirculation.