Background: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with bradyarrhythmias. We sought to examine the nature of conduction system abnormalities and the indications and determinants of anti-bradycardia pacing in patients with AFD.
Methods and results: We studied 204 patients with AFD (49% male, mean age 42 years) in an observational, longitudinal, retrospective cohort study. At baseline, 5 (2.5%) patients had pacemakers for the treatment of bradycardias [4/5 (80%) for atrioventricular disease; 1/5 (20%) for sinus node disease]. PR interval <120 ms was observed in 15 (7%); PR interval >200 ms in 6 (3%); QRS interval >120 ms 18 (9%); left QRS axis deviation in 16 (8%); and right-axis deviation in 2 (1%). Age was an independent determinant of prolonged PR interval, QRS duration and left QRS axis deviation. During follow-up (189 patients; 899 patient-years), 12 (6%) had a device implanted to treat spontaneously occurring bradyarrhythmias [5/12 (42%) for atrioventricular disease; 7/12 (58%) sinus node disease] with 8% 5-year cumulative incidence. Two independent predictors of future anti-bradycardia pacing were identified in a multivariable Cox model: QRS duration [hazard ratio (HR) 1.05, 95% confidence intervals (CI) 1.02-1.09, P= 0.001; receiver operating characteristic (ROC) curve c-statistic 0.726] and PR interval duration (HR 1.03, 95% CI 1.004-1.060, P = 0.023; ROC curve c-statistic 0.548). QRS duration ≥110 ms at baseline had a sensitivity of 64%, specificity of 84%, 49% positive predictive value, and 91% negative predictive value for identifying patients likely to require anti-bradycardia pacing.
Conclusion: In patients with AFD increasing age is associated with PR and QRS interval prolongation and left QRS axis deviation. Pacing for atrioventricular and sinus node disease is common and patients with QRS≥110 ms should be closely monitored for bradyarrhythmias.