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. 2025 Jan 21;12(1):e003055.
doi: 10.1136/openhrt-2024-003055.

Prognostic role of con-/discordant coronary flow reserve and microvascular resistance in coronary microvascular disease: a systematic review and network meta-analysis

Jin Al-Gully #  1   2 , Federico Oliveri #  1 , Jessica Parisa Forouzanfar  1   2 , Jose Manuel Montero-Cabezas  1 , Johan Wouter Jukema  1   3 , Melina Cynthia den Haan  1   2 , Ibtihal Al Amri  1   2 , Brian Oscar Bingen  4   2
Affiliations

Prognostic role of con-/discordant coronary flow reserve and microvascular resistance in coronary microvascular disease: a systematic review and network meta-analysis

Jin Al-Gully et al. Open Heart. .

Abstract

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.

Keywords: Angina Pectoris; Chest Pain; Coronary Angiography; Meta-Analysis; Microvascular Angina.

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Conflict of interest statement

Competing interests: The Department of Cardiology of the Leiden University Medical Center received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. JMM-C received a research grant from Shockwave Medical and Speaker fees from Penumbra, Abiomed and Boston Scientific.

Figures

Figure 1
Figure 1. Forest plot of major adverse events (MACE) rate in coronary microvascular disease (CMD) subgroups compared with group A. CFR, coronary flow reserve; MR, microvascular resistance.
Figure 2
Figure 2. Forest plot of cardiovascular (CV) death rate in coronary microvascular disease (CMD) subgroups compared with group A. CFR, coronary flow reserve; MR, microvascular resistance.
Figure 3
Figure 3. Forest plot of all-cause mortality in coronary microvascular disease (CMD) subgroups compared with group A. CFR, coronary flow reserve; MR, microvascular resistance.
Figure 4
Figure 4. Summary of coronary microvascular disease (CMD) subgroup characteristics based on con-/discordance of coronary flow reserve (CFR) and microvascular resistance (MR). BMI, body mass index; CBF, coronary blood flow; MACE, major adverse cardiovascular events.
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