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The prognostic value of coronary flow reserve in patients with non-obstructive coronary artery disease and microvascular dysfunction: a systematic review and meta-analysis with focus on imaging modality and sex difference

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Abstract

To clarify prognosis of patients with non-obstructive coronary artery disease (NOCAD) and coronary microvascular disease (CMD) assessed as low coronary flow reserve (CFR) according to imaging modalities and sex difference. Comprehensive systematic literature review and meta-analyses were conducted. Risk of death and major adverse cardiac events (MACE) were pooled and compared in patients with abnormally low versus normal CFR using cut-off limits 2.0–2.5. Random effects model used for estimation of odds ratios (OR) and hazard ratios (HR) with 95% confidence interval (CI). Nineteen eligible observational studies provided data for death and MACE, publication bias was insignificant, p = 0.62. Risk of death and MACE were significantly higher in patients with low (n = 4.612, 29%) than normal CFR (n = 11.367, 71%): using transthoracal echocardiography (TTE) (OR 4.25 (95% CI 2.94, 6.15) p < 0.001) and (OR 6.98 (95% CI 2.56, 19.01) p < 0.001), positron emission tomography (PET) (OR 2.51 (CI 95%: 1.40, 4..49) p = 0.002) and (OR 2.87 (95% CI 2.16, 3.81) p < 0.001), and invasive intracoronary assessment (OR 2.23 (95% CI 1.15, 4.34) p < 0.018), and (OR 4.61 (95% CI 2.51, 8.48) p < 0.001), respectively. Pooled adjusted HR for death and MACE were (HR 2.45(95% CI 1.37, 3.53) p < 0.001) and (HR 2.08 (95% CI 1.54, 2.63) p < 0.001) respectively. Studies comparing men and women with abnormally low CFR demonstrated similar worse prognosis in both sexes. Low CFR is associated with poorer prognosis in patients with NOCAD regardless of sex. TTE may overestimate risk of death and MACE, while PET seems to be more appropriate. Future studies are needed to consolidate the current evidence.

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Funding

This study was not funded by any organization or medical industry. The authors declare that they have no financial interests that are directly or indirectly related to this paper submitted for publication.

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  1. Department of Medicine, Section of Cardiology, Glostrup University Hospital of Copenhagen, Valdemar Hansens vej 1, 2600, Glostrup, Denmark

    Signe Miang Jensen & Jawdat Abdulla

  2. Department of Cardiology, Bispebjerg Frederiksberg Hospital, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark

    Eva Irene Bossano Prescott

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All authors contributed to the study conception and design. Material preparation, searching, data collection and analysis were performed by JA and SMJ. Prof. EP contributed with critical review of the whole work and the manuscript. The first draft of the manuscript was written by JA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jawdat Abdulla.

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10554_2023_2948_MOESM1_ESM.jpg

Supplementary file1 (PDF 33 KB)—Funnel plot of publications bias for fifteen studies estimating major adverse cardiac events (MACE). Egger’s test showed insignificant bias, p=0.62. S.e of log= standard error of log, logor= log of odds ratio.

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Jensen, S.M., Prescott, E.I.B. & Abdulla, J. The prognostic value of coronary flow reserve in patients with non-obstructive coronary artery disease and microvascular dysfunction: a systematic review and meta-analysis with focus on imaging modality and sex difference. Int J Cardiovasc Imaging 39, 2545–2556 (2023). https://doi.org/10.1007/s10554-023-02948-1

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