Arrhythmia and Clinical Outcomes in Fabry Cardiomyopathy and Nephropathy

Both cardiomyopathy and nephropathy represent hallmark manifestations of Fabry disease (FD), evidence remains limited regarding cardiovascular risk stratification based on organ-specific involvement patterns. In this retrospective cohort study of FD patients from the First Affiliated Hospital of Zhejiang University, we evaluated associations between cardiac/renal involvement and major cardiovascular events, including: 1) cardiovascular mortality, 2) new-onset severe heart failure (NYHA class III/IV), 3) incident atrial fibrillation, and 4) significant arrhythmia requiring device implantation. Patients were stratified into four phenotypic groups: non-affected (24.1%, n = 20), cardiac-only (24.1%, n = 20), renal-only (18.1%, n = 15), and co-affected (33.7%, n = 28). During a median follow-up of 39 months, 36.1% (n = 30) reached the primary endpoint. The cohort demonstrated substantial arrhythmia burden with significant intergroup differences (p < 0.05). Univariate Cox analysis revealed both left ventricular maximum wall thickness (LVMWT; HR: 1.176, 95% CI: 1.050–1.336, p = 0.010) and estimated glomerular filtration rate (eGFR; HR: 0.978, 95% CI: 0.962–0.992, p < 0.001) as continuous variables were significantly associated with outcomes. However, multivariate analysis confirmed only LVMWT as an independent predictor (p = 0.030), while eGFR lost significance (p = 0.480). These findings demonstrate that organ involvement patterns critically influence cardiovascular prognosis in FD, providing a framework for refined risk stratification.