Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.
L, C., XR, Y., Y, J., SQ, C., ZX, W., JW, W., MT, C., YY, L., G, L., & MN, L. (2026). Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.. Apoptosis : an international journal on programmed cell death. https://doi.org/10.1007/s10495-026-02376-1
L C, XR Y, Y J, SQ C, ZX W, JW W, et al. Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.. Apoptosis : an international journal on programmed cell death. 2026; doi: 10.1007/s10495-026-02376-1
L C, XR Y, Y J, et al. Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.[J]. Apoptosis : an international journal on programmed cell death. 2026. DOI: 10.1007/s10495-026-02376-1.
@article{l2026,
author = {Chen L and Yang XR and Jiang Y and Cheng SQ and Wan ZX and Wu JW and Chen MT and Li YY and Luo G and Liu MN},
title = {Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.},
journal = {Apoptosis : an international journal on programmed cell death},
year = {2026},
doi = {10.1007/s10495-026-02376-1},
note = {PMID: 42213282},
}
TY - JOUR AU - Chen L AU - Yang XR AU - Jiang Y AU - Cheng SQ AU - Wan ZX AU - Wu JW AU - Chen MT AU - Li YY AU - Luo G AU - Liu MN TI - Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications. T2 - Apoptosis : an international journal on programmed cell death PY - 2026 DO - 10.1007/s10495-026-02376-1 AN - PMID:42213282 ER -
Heart failure (HF) is a heterogeneous clinical syndrome characterized by phenotype-specific metabolic remodeling (e.g., ischemic vs. nonischemic, HF with HFrEF vs. HFpEF), with impaired metabolic flexibility serving as a central pathophysiological link. The physiological basis of normal cardiac metabolic flexibility is outlined, and the temporal trajectories and molecular mechanisms of metabolic remodeling across compensated, early decompensated, and end-stage HF are delineated. Key mechanisms, including dysregulated mitochondrial quality control, imbalanced substrate utilization, and transcriptional dysregulation are examined. Furthermore, multidimensional metabolic therapeutic strategies are summarized, and the translational potential of novel biomarkers (e.g., ketone bodies, acylcarnitines) is discussed. It is indicated the efficacy of metabolic therapies depends critically on HF phenotype, disease stage, and global metabolic network integrity. Future research is prioritized metabolomics-based precise phenotyping, dynamic monitoring of remodeling trajectories, and the development of systematic regulatory strategies featuring multi-target combinations and cardiac-specific delivery, so as to advance the clinical translation of metabolic therapies for HF.