Cardiac microcurrent therapy in heart failure: Mechanistic rationale, early clinical evidence, and future directions

Abstract
Despite major advances in guideline-directed medical therapy (GDMT), many patients with heart failure with reduced ejection fraction (HFrEF) remain symptomatic, with persistent limitations in functional capacity and health status, underscoring the need for adjunctive therapeutic strategies. Direct cardiac microcurrent (C-MIC) therapy is a non-excitatory bioelectrical intervention device to modulate myocardial remodeling rather than rhythm or acute contractility. C-MIC therapy influence myocardial biology, including pathways related to fibrosis, inflammation, and cellular homeostasis by delivering continuous, subthreshold direct current. Preclinical studies across cardiomyocytes, animal models, and cardiac fibroblasts suggest that microcurrent exposure may attenuate profibrotic signaling, regulate extracellular matrix turnover, and improve calcium handling, providing a mechanistic rationale for reverse remodeling. Early clinical experience, including first-in-human studies and a randomized trial in carefully selected patients with non-ischemic HFrEF, demonstrates feasibility and a consistent signal of improvement in left ventricular function, functional capacity, and patient-reported outcomes. However, the current evidence base remains limited by small sample size, open-label designs, and the absence of sham-controlled evaluation. All available clinical data are derived from surgically implanted systems, and the effectiveness of less invasive configurations remains uncertain. Accordingly, C-MIC should be considered an investigational therapy. Future development will require rigorous mechanistic validation, optimization of device programming and delivery parameters, and confirmation of efficacy in adequately powered, sham-controlled trials to define its role in contemporary HF management.

Conclusion
C-MIC therapy represents a novel bioelectrical approach to HF treatment that is mechanistically distinct from conventiona rhythm- or contractility-based device therapies. Preclinical studies support a biologically plausible role in modulating fibrosis, inflammation and myocardial remodeling. Early clinical studies suggest feasibility and a consistent signal of improvement in left ventricular function, symptoms, and functional capacity in carefully selected patients with non-ischemic HFrEF. However, current evidence remains limited by small sample sizes, open-label study designs, and the absence of sham-controlled evaluation. The future role of C-MIC therapy will depend on rigorous mechanistic validation, confirmation of efficacy in adequately powered controlled clinical trials and identification of the patient phenotypes most likely to derive meaningful clinical benefit.