Metabolic Modulation in Dilated Cardiomyopathy: From Pathophysiology to Therapy.

This review aims to synthesize current evidence on the role of cardiac energy metabolism in the pathogenesis of dilated cardiomyopathy (DCM), with a focus on myocardial blood flow, substrate utilization, genetic and metabolic pathways, and potential energy-targeted therapeutic strategies. DCM involves structural and functional impairments of the myocardium, often linked to genetic mutations (e.g., in titin (TTN) and lamin) or acquired factors, including infection, alcohol, drugs, and endocrine disorders. Moreover, the disruption of cardiac energy homeostasis is central to the pathogenesis of DCM, characterized by compromised energy supply, altered substrate metabolism, and reduced adenosine triphosphate (ATP) production, all of which collectively contribute to contractile dysfunction and disease progression. Emerging evidence indicates that impaired myocardial energetics, including reduced coronary blood flow, shifts in fuel utilization, and dysregulation of energy metabolic pathways, are hallmark features of DCM. Nonetheless, energy deficiency is increasingly being recognized as a key driver of DCM development and heart failure. Cardiac energy metabolic disruption is intimately involved in the pathophysiology of DCM and represents a promising target for novel therapeutic interventions. Current management strategies often overlook metabolic aspects; therefore, this review highlights the need to integrate energy-based approaches into the treatment paradigm for DCM.