Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF

Yun, Hyeong Rok; Singh, Manish Kumar; Han, Sunhee; Ranbhise, Jyotsna S.; Ha, Joohun; Kim, Sung Soo; Kang, Insug

doi:10.3390/ijms27020879

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Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF

by

Hyeong Rok Yun

^1,2,

Manish Kumar Singh

^1,2

,

Sunhee Han

^2,3,

Jyotsna S. Ranbhise

^2,3

,

Joohun Ha

^1,2,3,

Sung Soo Kim

^1,2,3,*

and

Insug Kang

^1,2,3,*

¹

Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

²

Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea

³

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(2), 879; https://doi.org/10.3390/ijms27020879

Submission received: 6 December 2025 / Revised: 7 January 2026 / Accepted: 14 January 2026 / Published: 15 January 2026

(This article belongs to the Special Issue Lipid Metabolism and Biomarkers in Neural and Cardiometabolic Health)

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Abstract

Cardiac metabolic flexibility is a key determinant of myocardial energetic resilience. In heart failure with reduced ejection fraction (HFrEF), intrinsic mitochondrial dysfunction and lipotoxicity compromise oxidative capacity. In contrast, heart failure with preserved ejection fraction (HFpEF) is orchestrated primarily by systemic comorbidities and coronary microvascular dysfunction, which decouple glycolysis from glucose oxidation. This review integrates these distinct pathophysiologies into a comprehensive biomarker framework. Beyond core hemodynamic markers, we detail indices of metabolic flux (ketones, acylcarnitines, branched-chain amino acids), endothelial injury, and fibrosis. We further prose a shift from static, isolated measurements to dynamic functional profiling using standardized challenges (e.g., mixed-meal or exercise tests) to quantify metabolic suppression and recovery kinetics. This structured hierarchy enables phenotype-tailored risk stratification and guides mechanism-based precision therapies in the era of personalized medicine.

Keywords: metabolic flexibility; heart failure; precision medicine; dynamic profiling

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MDPI and ACS Style

Yun, H.R.; Singh, M.K.; Han, S.; Ranbhise, J.S.; Ha, J.; Kim, S.S.; Kang, I. Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF. Int. J. Mol. Sci. 2026, 27, 879. https://doi.org/10.3390/ijms27020879

AMA Style

Yun HR, Singh MK, Han S, Ranbhise JS, Ha J, Kim SS, Kang I. Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF. International Journal of Molecular Sciences. 2026; 27(2):879. https://doi.org/10.3390/ijms27020879

Chicago/Turabian Style

Yun, Hyeong Rok, Manish Kumar Singh, Sunhee Han, Jyotsna S. Ranbhise, Joohun Ha, Sung Soo Kim, and Insug Kang. 2026. "Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF" International Journal of Molecular Sciences 27, no. 2: 879. https://doi.org/10.3390/ijms27020879

APA Style

Yun, H. R., Singh, M. K., Han, S., Ranbhise, J. S., Ha, J., Kim, S. S., & Kang, I. (2026). Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF. International Journal of Molecular Sciences, 27(2), 879. https://doi.org/10.3390/ijms27020879

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Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF

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