Meta-analysis of 20 years of research on mortality and sudden cardiac death in Fabry disease: more fear than fatalities?

Introduction Fabry disease (FD) is a rare X-linked storage disorder marked by delayed diagnosis and a relevant number of undetected cases. Multi-organ involvement also includes cardiomyopathy, with dedicated treatment for FD leading to improved patient outcomes. However, despite these improvements, mortality rates related to sudden cardiac death (SCD) remain poorly quantified in this population. Purpose The present meta-analysis aimed to quantify SCD and mortality in FD patients. Methods A systematic literature search was performed including studies from PubMed and Cochrane from January 01, 2005, to February 24, 2025. The following search items were used: "sudden cardiac death", "death", "ventricular arrhythmia", "Anderson Fabry disease", and "Fabry disease". Statistical analysis comprised Hartung-Knapp adjustment for random effects model, logit transformation and Clopper-Pearson confidence interval. Results A total of 400 studies were identified (n=371 Pubmed, n=29 Cochrane). After excluding case reports, reviews, meta-analyses, and studies that did not report follow-up periods or any SCD cases, we included 11 studies in the current meta-analysis. The studies comprised four retrospective and seven prospective observational studies with a total of 651 patients and 68 death including 38 SCD (Figures 1 and 2). The overall annual mortality rate was 2.0%, with 1.3% attributed to SCD during a mean follow-up duration of 6.9±2.7 years. Conclusion Overall, in our current meta-analysis of studies from the last 20 years, Fabry disease demonstrated relatively low mortality rates, particularly for SCD, which may be related to improvements in specialized care.Figure 1 Figure 2