Research progress on metabolic abnormalities in myocardial hypertrophy

Myocardial hypertrophy is initially an adaptive response to mechanical, neurohumoral, or metabolic stress, but persistent hypertrophy increases the risk of heart failure, arrhythmia, and death. Metabolic remodeling is now recognized as an early driver rather than a passive consequence of increased workload. This review aims to summarize recent advances in metabolic abnormalities in myocardial hypertrophy, focusing on pathophysiological mechanisms, biomarker implications, therapeutic opportunities, and future directions. Current evidence establishes that hypertrophic myocardium exhibits substrate inflexibility, impaired fatty acid oxidation, increased glycolysis with anaplerotic rerouting, mitochondrial calcium and quality-control defects, NAD⁺-sirtuin disruption, redox stress and ferroptosis, branched-chain amino acid accumulation, and ketone body adaptation. These abnormalities interact with canonical growth pathways including AMPK, mTOR, PKA, YAP, STAT3, ERR, SIRT3/SIRT5/SIRT6, and inflammatory programs. In biomarker research, metabolomics has moved from single metabolites toward integrated panels combining circulating acylcarnitines, amino acids, ketones, redox markers, and imaging-derived hypertrophy; however, interpretation remains strongly context-dependent on etiology, disease stage, sex, renal function, diabetes, and therapy. Therapeutically, phenotype-specific strategies-such as NAD⁺ repletion, SIRT activation, BCAA catabolism modulation, and ferroptosis inhibition-are emerging but require biomarker-guided trials. Despite these advances, critical challenges remain: distinguishing adaptive compensation from maladaptive remodeling, validating tissue-to-plasma concordance, establishing longitudinal human cohorts with serial metabolomics, and developing harmonized multi-omics pipelines. By addressing these core issues, this review provides a comprehensive, clinically oriented perspective on the current state and future trajectory of metabolic research in myocardial hypertrophy, emphasizing the need for biomarker-enriched interventions before irreversible remodeling occurs.