Sudden cardiac death and major arrhythmic events in patients with Fabry disease: Risk stratification in the French Heart Fabry cohort multicenter study.

BACKGROUND

Fabry disease (FD) is a rare X-linked genetic disorder owing to α-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

This study aimed to evaluate the incidence of arrhythmic events and identify potential predictive factors in patients with FD.

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 (MAEs) were defined as sudden cardiac death, sustained ventricular arrhythmia, high-degree atrioventricular block, or appropriate implantable cardioverter-defibrillator 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 2 significant predictors of MAE: nonsustained ventricular tachycardia (hazard ratio 9.37; 95% confidence interval [CI] 1.57-56.06; P = .014) and age >55 years (hazard ratio 16.99; 95% CI 1.98-156; P = .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 (95% CI 0.60-1), indicating stable discriminative performance with minimal overfitting. The 5-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.