Heart Rhythm. 2026 May 15:S1547-5271(26)02388-X. doi: 10.1016/j.hrthm.2026.05.021. Online ahead of print.
ABSTRACT
BACKGROUND: Fabry disease (FD) is a rare X-linked genetic disorder due to alpha-galactosidase deficiency. Cardiovascular complications, including ventricular arrhythmias and conduction abnormalities, constitute the major causes of mortality. However, risk stratification for arrhythmic events in FD remains unclear.
OBJECTIVE: To evaluate the incidence of arrhythmic events and identify potential predictive factors in FD patients.
METHODS: Cardiovascular complications were studied during the entire life of patients and during follow-up after FD diagnosis in a retrospective, multicenter study: the French Heart Fabry cohort. Major arrhythmic events (MAE) were defined as sudden cardiac death, sustained ventricular arrhythmia, high-degree AV block or appropriate ICD therapy.
RESULTS: Of 160 adult patients with FD included in the study (mean age 41.0 years, 47% male), 69 (43%) over their lifespan exhibited arrhythmic and/or conduction disturbances, predominantly supraventricular arrhythmias. Over 5 years of follow-up after diagnosis in 145 patients, MAE occurred in 9 (6.25%). After multivariate analysis, we identified two significant predictors of MAE: non-sustained ventricular tachycardia (HR = 9.37 [1.57-56.06], p = 0.014) and age beyond 55 years (HR = 16.99 [1.98-156], p =0.012). The C-index of the model for predicting MAE was 0.82 (95% CI, 0.61-0.96). After bootstrap internal validation, the optimism-corrected C-index was 0.81 [0,60-1], indicating stable discriminative performance with minimal overfitting. The five-year cumulative incidence of MAE was 1.8% (95% CI, 0.2-6.5), 7.9% (95 CI, 1.7-21.4), and 44.4% (95% CI, 13.7-78.8) among patients with 0, 1 and 2 risk factors, respectively.
CONCLUSION: The incidence of arrhythmic events is high in this FD cohort. A risk prediction for MAE was developed, which may improve preventive therapeutic decisions.
PMID:42142859 | DOI:10.1016/j.hrthm.2026.05.021