Pharmacological Insights and Clinical Challenges of Wenxin Keli in Arrhythmia Treatment.

Cardiac arrhythmias remain a leading cause of cardiovascular morbidity and mortality worldwide. Although conventional antiarrhythmic drugs are effective, their use is constrained by proarrhythmic risks and extracardiac toxicity. Wenxin Keli (WXKL), a traditional Chinese medicine (TCM) formula, has demonstrated antiarrhythmic properties in preclinical and clinical studies with a reportedly favorable safety profile. This article provides a critical synthesis of WXKL's pharmacological mechanisms, including ion channel modulation (INa, ICaL, Ito), calcium handling, and calcium/calmodulin-dependent protein kinase II signaling, with explicit appraisal of translational limitations. Clinical trial evidence and meta-analyses for atrial fibrillation (AF), premature ventricular contractions, and other indications were systematically evaluated, with detailed discussion of effect sizes, heterogeneity, and methodological quality. Key challenges unique to WXKL as a TCM-derived product-formulation variability, quality control limitations, and regulatory approval pathways-are analyzed in depth. A prioritized research agenda is proposed to address evidence gaps. *These authors contributed equally to this work and share first authorship.