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Subclinical hepatic fibrosis is associated with coronary microvascular dysfunction by myocardial perfusion reserve index: a retrospective cohort study

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Abstract

The heart–liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3 years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] − 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart–liver disease.

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Data availability

The datasets used during this study are available from the corresponding author on reasonable request.

Consent for publication

Not applicable.

Abbreviations

APRI:

AST to platelet ratio

CMR:

Cardiac magnetic resonance imaging

ECV:

Extracellular volume

Fib-4:

Fibrosis-4 score

HFpEF:

Heart failure with preserved ejection fraction

LVEF:

Left ventricular ejection fraction

LVMI:

Left ventricular mass index

MPRI:

Myocardial perfusion reserve index

NAFLD-FS:

Non-alcoholic fatty liver disease fibrosis score

RWT:

Relative wall thickness

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Funding

This work was supported in part by the Doris Duke Charitable Foundation Grant 2020059 (ACK), the Barbra Streisand Women’s Cardiovascular Research and Education Program (CNB), the Linda Joy Pollin Women’s Heart Health Program (NCB), the Erika Glazer Women’s Heart Health Project (CNB), the Walter R. Ferguson Charitable Fund (CNB), and the Adelson Family Foundation (CNB).

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Authors and Affiliations

  1. Division of Digestive and Liver Diseases, and Department of Imaging, Barbra Streisand Women’s Heart Center, Biomedical Imaging Research Institute, Smidt Heart Institute Department of Cardiology, Cedars Sinai Medical Center, 127 S San Vicente Blvd #A3600, Los Angeles, CA, 90048, USA

    Alan C. Kwan, Janet Wei, Eric Luong, Gerran Salto, Trevor-Trung Nguyen, Patrick G. Botting, Yunxian Liu, David Ouyang, Joseph E. Ebinger, Debiao Li, Mazen Noureddin, Louise Thomson, Daniel S. Berman, C. Noel Bairey Merz & Susan Cheng

  2. Department of Medicine, Keck School of Medicine of USC, Los Angeles, USA

    Brian P. Lee

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  1. Alan C. Kwan
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Contributions

ACK: Conception, design, analysis, interpretation, drafting, review; JW: Conception, interpretation, review; BPL: Conception, design, interpretation, review; EL: Conception, acquisition, analysis, interpretation, review; GS: Conception, acquisition, analysis, review; TTN: Conception, acquisition, analysis, review; PGB: Design, analysis, interpretation, review; YL: Design, analysis, review; DO: Conception, design, interpretation, review; JEE: Conception, design, interpretation, review; DL: Conception, design, interpretation, review; MN: Conception, interpretation, review; LT: Conception, interpretation, review; DSB: Conception, acquisition, interpretation, review; CNB: Conception, acquisition, interpretation, review; SC: Conception, design, acquisition, analysis, interpretation, review. All authors have approved the final version and agree to accountability for author’s contributions.

Corresponding author

Correspondence to Alan C. Kwan.

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Conflict of interest

Dr, Merz serves on the Board of Directors for iRhythm and has received fees paid through Cedars-Sinai Medical Center from Abbott Diagnostics and Sanofi. Dr. Wei has served on an advisory board for Abbott Vascular. The other authors report no relevant conflicts.

Ethical approval

Study was approved by Cedars Sinai IRB.

Informed consent

Informed consent waived due to retrospective study.

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Kwan, A.C., Wei, J., Lee, B.P. et al. Subclinical hepatic fibrosis is associated with coronary microvascular dysfunction by myocardial perfusion reserve index: a retrospective cohort study. Int J Cardiovasc Imaging 38, 1579–1586 (2022). https://doi.org/10.1007/s10554-022-02546-7

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  • DOI: https://doi.org/10.1007/s10554-022-02546-7

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