From moderate to strenuous training: unravelling mechanistic contributors and biomarkers for atrial fibrillation in exercise

The impact of the transition from moderate to strenuous exercise on atrial fibrillation (AF) risk and its underlying mechanisms remain poorly understood. We aimed to analyse biatrial remodelling after moderate and strenuous exercise, compare it with pathological atrial damage, and non-invasively identify strenuous exercise insults.

Young male Wistar rats were trained at a moderate (MOD) or high-intensity (INT) load; sedentary rats served as controls. After 16 weeks, electrophysiological and echocardiographic studies were obtained, and atrial samples were used for fibrosis quantification. Plasmatic biomarkers (at rest and after exercise) and atrial gene expression (mRNA array) were assessed. Results were compared with a transverse aortic constriction (TAC) model.

AF inducibility progressively increased with exercise load. Both trained groups presented bradycardia, an enhanced parasympathetic tone and biatrial dilatation. INT rats exhibited prolonged P-waves and greater fibrosis in the left (LA) and right atria (RA). The proarrhythmogenic remodelling substantially differed in both atria. Compared with MOD, inflammatory pathways were enriched in the RA of INT, similar to the TAC model. Only minor changes were observed after exercise in the LA. Plasma biomarkers showed unremarkable changes between groups at rest, but intensive exercise led to a transient increase in proinflammatory markers.

Exercise-induced-AF pathology is load-dependent: parasympathetic tone augmentation and atrial dilatation drive AF risk in moderately trained rats, whereas a further increase is associated with atrial fibrosis. Transient inflammation, identifiable through plasma biomarkers, could underpin AF susceptibility and fibrosis in the RA of INT rats, and serve as biomarkers.