Cardiac Remodeling Trajectory and Renal Stage–Specific Risk Stratification in East Asian Fabry Disease Patients

BACKGROUND: Static anatomical assessments may not fully capture the dynamic progression and varied clinical outcomes in Fabry cardiomyopathy. OBJECTIVES: The authors aimed to evaluate the prognostic value of objective cardiac remodeling trajectories and renal stage-specific structural thresholds. METHODS: In this cohort of 105 patients with Fabry disease, longitudinal remodeling velocity was quantified using the linear mixed model-derived anatomical cardiac raw score (aCRS) slope. The primary outcome was a composite endpoint of heart failure hospitalization or cardiovascular death. Prognostic associations were assessed using Firth's penalized Cox regression to account for low event counts. RESULTS: Over a median follow-up of 41 months (IQR: 25-58 months), the composite endpoint incidence was 19.0% (95% CI: 12.0%-27.9%). Firth's Cox regression revealed that a higher baseline aCRS (HR: 1.462; 95% CI: 1.213-1.813; P < 0.001) and a steeper aCRS slope (HR: 1.020; 95% CI: 1.001-1.037; P = 0.044) independently predicted adverse outcomes. Enzyme replacement therapy was significantly protective (HR: 0.342; 95% CI: 0.131-0.881; P = 0.027). Furthermore, baseline risk stratification demonstrated a cardiorenal threshold shift, requiring a higher structural cutoff (aCRS ≥3) in moderate-to-severe renal impairment compared to preserved renal function. CONCLUSIONS: Objective cardiac remodeling velocity is a significant predictor of adverse clinical outcomes in Fabry disease. Integrating dynamic structural trajectories with renal stage-specific adaptations provides a reliable framework for personalized risk stratification.