Key result
Concordantly abnormal CFR and microvascular resistance are linked to ~2.3-fold higher all-cause mortality.
Why the study?
Coronary microvascular disease definitions permit discordant CFR and MR values, but the prognostic value and pathophysiological backgrounds of CFR and MR con- and discordance remain to be characterised.
Does abnormal coronary flow reserve and/or abnormal microvascular resistance predict all-cause mortality and MACE in patients without significant epicardial coronary artery disease?
Meta-Analysis (n=2,310)
Yes
Does abnormal coronary flow reserve and/or abnormal microvascular resistance predict all-cause mortality and MACE in patients without significant epicardial coronary artery disease?
Odds Ratio: 2.27 (95% CI 1.12–4.58)
Concordantly abnormal CFR and MR identifies a high-risk subset of coronary microvascular disease, suggesting that the current uniform definition of CMD should be refined for better prognostic stratification.
BACKGROUND: Coronary microvascular disease (CMD) is defined as impaired coronary flow reserve (CFR) and/or increased microvascular resistance (MR) without significant epicardial coronary stenosis. This definition allows for discordant CFR and MR values within patients with CMD. The aim of this meta-analysis is to characterise the prognostic value and pathophysiological backgrounds of CFR and MR con-/discordance. METHODS: A systematic search (PROSPERO CRD42024573004) identified studies determining CFR and MR in patients without significant epicardial coronary artery disease. Patients were divided into four groups: (1) normal CFR and MR, (2) abnormal CFR and MR, (3) abnormal CFR with normal MR and (4) normal CFR with abnormal MR and analysed for all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: We identified four studies representing 2310 total participants. Group B had the highest MACE (OR: 3.23; 95% CI 1.95 to 5.36) and mortality rate (OR: 2.27; 95% CI 1.12 to 4.58) compared with group A. Group C, associated with female sex, showed significantly higher MACE (OR: 2.07; 95% CI 1.25 to 3.45) but not mortality (OR: 1.89; 95% CI 0.92 to 3.88) compared with group A. In group D, associated with high body mass index, MACE and mortality rates did not differ significantly from group A (OR: 1.19; 95% CI 0.67 to 2.11 and OR: 0.55; 95% CI 0.16 to 1.90, respectively). CONCLUSIONS: Abnormal CFR and MR are associated with a high risk of MACE and death. Abnormal CFR and normal MR are associated with an increased MACE-but not death. MACE and mortality risk in discordantly normal CFR and abnormal MR are low. Our findings show the need for tailoring CFR and MR diagnostic thresholds to patient characteristics and raise questions about the presence of CMD in patients with abnormal MR with normal CFR.
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Al-Gully et al. (2025) conducted a meta-analysis in Coronary microvascular disease (CMD) (n=2,310). Concordantly abnormal coronary flow reserve (CFR) and microvascular resistance (MR) vs. Concordantly normal CFR and MR was evaluated on All-cause mortality (OR 2.27, 95% CI 1.12-4.58). Concordantly abnormal coronary flow reserve and microvascular resistance were associated with a significantly higher risk of all-cause mortality (OR 2.27, 95% CI 1.12-4.58) compared to normal values.
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