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.