Microcurrent Therapy in Cardiac Repair: Bridging Mechanistic Biology and Clinical Evidence

Abstract
Cardiovascular disease remains a major cause of morbidity and mortality, with heart failure representing the common and often irreversible end stage, for which current therapies are largely palliative rather than restorative. Cardiac microcurrent therapy delivers a low-intensity, nondepolarizing direct current across the myocardium and has been proposed to modulate fibrosis, inflammation, and remodeling in heart failure with reduced ejection fraction. In Cardiac Microcurrent I (New York Heart Association III nonischemic heart failure with reduced ejection fraction), left ventricular ejection fraction increased by 12.6% at 6 months, 6-minute walk distance improved by 191 m, and 8 of 10 patients improved to New York Heart Association I within 2 weeks. In the randomized Cardiac Microcurrent II trial, patients showed further improvements, including a 5.1% increase in left ventricular ejection fraction, a reduction in New York Heart Association class (up to 69%), and a 38 m increase in 6-minute walk distance. However, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels did not show a consistent corresponding reduction. In vitro, microcurrent altered the myofibroblast phenotype and reduced the expression of transforming growth factor-β1, collagen, α-smooth muscle actin, and fibronectin. Transcriptomics revealed downregulation of inflammatory and immune pathways, while cardiomyocytes from spontaneously hypertensive rats exhibited enhanced survival and stress resistance. This review combines early clinical observations and preclinical findings to examine potential mechanisms of action and bioelectrical effects of cardiac microcurrent therapy. Given the limited clinical evidence and largely in vitro nature of the data, the current mechanistic findings should be considered preliminary. We highlight key knowledge gaps and propose future studies to define molecular mechanisms, discover biomarkers, analyze key signaling pathways, and evaluate clinical outcomes in adequately powered, sham-controlled trials, which could further validate this therapeutic approach.

Conclusions
Microcurrent therapy is a promising approach to cardiac repair through modulation of endogenous bioelectric signals. Preclinical studies suggest potential effects on fibrosis, inflammation, and cardiomyocyte survival in vitro, supporting a multifactorial mechanism of action. However, the underlying signaling pathways remain incompletely understood, and their relevance to human tissue has yet to be established. Continued investigation in physiologically relevant preclinical models, together with rigorous controlled clinical studies, will be essential to further define the mechanisms of action, validate the biological effects observed to date, and determine the therapeutic potential of microcurrent therapy in heart failure and other cardiovascular diseases.