Myocardial Metabolism and Postoperative Risk Stratification in Cardiac Surgery: A Narrative Review and Conceptual Framework

Postoperative complications following cardiac surgery remain a significant source of morbidity and mortality despite substantial advances in operative technique and perioperative care, underscoring the need for more precise and individualized risk stratification strategies. Existing prediction models rely primarily on demographic variables, comorbid conditions, and structural measures of cardiac function. However, they do not account for myocardial energetic resilience or the heart's capacity to tolerate ischemia-reperfusion injury and hemodynamic stress. Myocardial metabolism, encompassing substrate utilization, mitochondrial oxidative phosphorylation, bioenergetic reserve, redox homeostasis, calcium handling, and inflammatory signaling, represents a biologically plausible and mechanistically relevant contributor to perioperative risk, though the strength and consistency of this relationship across study types remain heterogeneous. Impairments in metabolic flexibility, reduced mitochondrial respiratory capacity, inefficient adenosine triphosphate (ATP) generation, and heightened oxidative stress have been associated with, though not consistently shown to predict directly, adverse postoperative outcomes, including low cardiac output syndrome, arrhythmias, prolonged inotropic support, and significant morbidity or mortality, even among patients with similar structural and demographic risk profiles. Emerging approaches to metabolic phenotyping, including noninvasive metabolic imaging, circulating metabolite and redox biomarker panels, and ex vivo mitochondrial functional assays, offer complementary pathways for quantifying myocardial energetic state; however, much of this evidence remains early-stage, indirect, or translational in nature, derived largely from preclinical models, small cohorts, or non-cardiac surgical populations, with limited standardization and prospective clinical validation to date. Collectively, the available mechanistic and early clinical evidence support further investigation into myocardial metabolic profiling as a potential adjunct to established clinical risk scores, rather than immediate clinical integration, with the longer-term potential to refine perioperative risk assessment, identify metabolically vulnerable patients with greater precision, and advance a physiology-driven, personalized framework for cardiac surgical care.