Cardiovascular prognostic determinants in anderson-fabry disease: insights from a multicenter cohort study

Abstract Background Despite growing recognition of Anderson-Fabry disease (AFD) as a multisystemic lysosomal disorder, comprehensive data on the pathophysiological determinants influencing cardiovascular outcomes remains poorly characterized. Furthermore, there persists a notable evidence gap regarding the distinctive patterns of cardiac involvement and their prognostic implications across the spectrum of renal impairment severity in Chinese AFD patients. Purpose This multicenter study aimed to evaluate cardiac involvement, prognostic determinants, and the predictive utility of the Cardiac Row Score (CRS), which is a pivotal component of the FAbry STabilization indEX (FASTEX) model, in 105 Chinese AFD patients. Methods Patients with FD from 3 Chinese tertiary hospitals were enrolled in this prospective, multicentre cohort. Patients were comprehensively evaluated by the row score of the cardiac scoring system, which compromised three core parameters: echocardiographic measurements, electrocardiographic findings, and New York Heart Association (NYHA) functional classification, providing an objective snapshot of a patient's current cardiac involvement severity. The staging of renal impairment severity was established according to albuminuria and estimated glomerular filtration rate (eGFR) (calculated using the CKD-EPI equation). Eligible patients who had an eGFR between 60-90 mL/min/1.73m² along with albuminuria 150 mg/day, or preserved renal function with eGFR ≥90 mL/min/1.73m² regardless of albumin levels were recognized as Stage1; Patients with moderately impaired renal function with eGFR ≥60 mL/min/1.73m² combined with significant albuminuria (500 mg/day), or mild-moderate functional decline (eGFR 25-90 mL/min/1.73m²) accompanied by moderate albumin excretion (150-500 mg/day) were categorized into Stage 2; The remaining patients were defined as stage 3. The primary outcome was a composite endpoint comprising cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Results A total of 105 patients were included. Over a median 41-month follow-up, 19% (n=20) reached the composite endpoint, predominantly heart failure hospitalizations (90%). Multivariate Cox regression confirmed CRS as an independent prognostic marker (adjusted HR=1.305 per 1-point increase, P=0.001), with high-risk patients (CRS5) exhibiting 2.4-fold increased risk. Notably, renal impairment severity stratified outcomes demonstrated progressive increases in composite endpoint incidence with advancing renal impairment stages (Stage 1: 9.8%5/51 vs Stage 2: 28.9%13/45 vs Stage 3: 22.2%2/9), though Stage 3 outcomes were comparable due to limited sample size (n=9). Conclusions This study advances the understanding of cardiac involvement in Chinese AFD patients, demonstrating the prognostic significance of CRS and the complex interplay between renal and cardiovascular disease.CENTRAL ILLUSTRATION