The Dual Nature of Sinoatrial Node Remodelling in Athletes: A Systematic Review of Electrophysiological Adaptations and the Pathological Tipping Point

运动员窦房结重构的双重特性:电生理适应和病理临界点的系统性综述

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Abstract

The "athlete's heart" phenotype, featuring resting bradycardia, has traditionally been viewed as a benign adaptation. However, emerging evidence associates prolonged, high-intensity endurance training with an increased risk of clinical sinoatrial node dysfunction. This systematic review synthesizes evidence on exercise-induced intrinsic Sinoatrial Node (SAN) electrophysiological remodelling and evaluates its dual nature along the adaptation-pathology continuum. Following PRISMA guidelines, a systematic search of PubMed, Web of Science, and Google Scholar (2000-2025) identified 17 eligible studies. Analysis revealed that in humans, rodents, and rabbits, exercise induces intrinsic SAN electrophysiological remodelling-a "membrane clock" reset characterized by coordinated downregulation of pacemaker currents, notably Hyperpolarization-activated cyclic nucleotide-gated cation channel (I(f)), via the Nkx2.5-miR-423-5p transcription factor pathway. Evidence for "calcium clock" involvement remains inconsistent. In contrast, large animal models (e.g., dogs, horses) show only parasympathetic-mediated bradycardia without intrinsic remodelling. Training loads may induce structural changes (e.g., fibrosis), providing an anatomical substrate for pathology. Moderating factors such as training type and ageing contribute to a phenotype of "acquired SAN reserve reduction. Exercise-induced intrinsic SAN remodelling is a physiological adaptation mechanism that, under certain conditions, can cross a threshold to become a pathological cause of clinical dysfunction. Recognizing this continuum is essential for risk stratification and future therapeutic innovation.

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