Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling

Heart failure (HF) is a complex clinical syndrome of progressive cardiac dysfunction, posing a major global burden on public health. The coupling between cardiomyocyte electrophysiology and energy metabolism is critical for sustaining cardiac electromechanical function. This review aims to elucidate the role of disrupted metabolic-electrophysiological coupling in disease progression and summarize emerging therapeutic targets.

Currently, drugs that correct electrical or metabolic issues are proving effective in patients, while theoretical research and preliminary experiments have corroborated electro-metabolic coupling and its regulatory crosstalk among metabolic signaling, electrical activity, and energy utilization. These foundational studies have established a viable basis for multi-target interventions in HF. Restoring the disrupted integration between metabolism and electrophysiology emerges as a promising strategic direction in HF therapy. Interventions targeting this integration, such as metabolic modulators and mitochondrially targeted agents, may suppress arrhythmias, reverse adverse remodeling, and improve contractile function. This integrated approach may ultimately lead to more effective treatments that improve clinical outcomes for HF patients.