Characteristics and outcomes of young atrial fibrillation patients with a normal heart: insights from a prospective cohort and database analysis

Atrial fibrillation (AF) is uncommon in young individuals without heart disease, and its clinical profile, associated risk factors, and prognosis in this group remain poorly defined compared to older patients.

This study aims to elucidate the demographic, familial, and phenotypic features of young AF patients and to evaluate their clinical management and long-term outcomes.

Since 2016, we have prospectively enrolled both prevalent and incident cases from two academic centres, comprising patients experiencing their first AF episode before the age of 40 in the absence of heart disease. This cohort was comprehensively evaluated for demographic, familial, phenotypic, and genotypic characteristics, as well as management strategies. Additionally, a separate cohort derived from the TriNetX Research Collaborative Network database was analysed to assess prognosis.

In the prospective cohort, 122 patients (mean age 31.2 ± 6.19 years) were included, with a predominance of males (84.4%). Notably, 89.3% had at least one modifiable risk factor: high-intensity exercise (27.0%), smoking (22.1%), excessive alcohol consumption (22.1%), or obesity (12.3%). Familial AF was identified in 15.6% of cases, and inherited cardiovascular conditions were observed in 23.8%. Among patients with familial AF who underwent genetic testing for arrhythmia and cardiomyopathy panels, all were found to carry genetic variants. At a median follow-up of 52.0 [20.8; 104.0] months post-diagnosis, rhythm control was successful in 62.5% of patients overall, with one-year success rates of 85.7% following one catheter ablation and 93.3% after two procedures. In the TriNetX database analysis, 26,805 patients with AF diagnosed before age 40 without structural heart disease were compared with 260,718 older AF patients, revealing a significantly higher lifelong risk of sudden cardiac death and ventricular arrhythmia in younger individuals (Hazard Ratio: 1.406 [1.294–1.529], p < 0.0001).

Young patients with AF and no heart disease are predominantly male and often have modifiable risk factors. A significant subset has an underlying potential genetic predisposition. While rhythm control strategies—particularly catheter ablation—demonstrate high success rates, the higher risk of lifelong ventricular arrhythmia and sudden cardiac death highlights the importance of long-term follow-up.

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