Baseline myocardial fibrosis in Fabry disease was associated with malignant ventricular arrhythmias (occurring in 27.1% of patients with fibrosis vs 0% without), and its annual increase independently predicted MVAs.
Cohort (n=73)
Does the burden and progression of myocardial fibrosis predict malignant ventricular arrhythmias in patients with Fabry disease?
In patients with Fabry disease, myocardial fibrosis is progressive and not apparently modified by enzyme replacement therapy, with its annual increase serving as an independent predictor of malignant ventricular arrhythmias.
Absolute Event Rate: 27.1% vs 0%
The aim of this study was to investigate the impact of myocardial fibrosis in Fabry disease. Seventy-three patients with genetically confirmed Fabry disease were followed for 4.8 ± 2.4 years. In accordance with current guidelines, 57 patients received enzyme replacement therapy (ERT) after study inclusion, whereas 16 did not. At baseline and latest possible follow-up, myocardial fibrosis was assessed noninvasively by cardiac magnetic resonance, and biomarkers of collagen metabolism were determined. Holter electrocardiography and clinical follow-up at yearly intervals were used to monitor malignant ventricular arrhythmias (MVAs; nonsustained and sustained ventricular tachycardia and sudden cardiac death). In total, 48 patients (66%) showed fibrosis assessed by late enhancement (LE) at baseline, and 4 patients developed new LE during follow-up, 2 of them despite ERT. The 2 patients receiving ERT (1.4 ± 1.9% vs 2.5 ± 2.6%, p <0.001) and the patients not receiving ERT (0.5 ± 0.8% vs 0.7 ± 1.0%, p = 0.035) showed a progression of LE during follow-up. None of the patients displayed reductions of LE during follow-up. Collagen biomarkers were elevated in patients with and without LE but did not correlate with LE amount. Thirteen LE-positive patients at the baseline examination had documented MVAs (including 5 sudden cardiac deaths), whereas none of the patients without LE had MVAs. The yearly increase in fibrosis was 0.9 ± 0.6% in patients with MVAs and 0.2 ± 0.3% in patients without MVAs (p <0.001). Logistic multivariate regression analysis revealed that the annual increase in fibrosis during follow-up was the only independent predictor of MVAs. In conclusion, myocardial fibrosis in Fabry disease is progressive, apparently not modified by ERT, and a crucial outcome determinant.
Krämer et al. (2014) conducted a cohort in Fabry disease (n=73). Myocardial fibrosis vs. No myocardial fibrosis was evaluated on Malignant ventricular arrhythmias (MVAs). Baseline myocardial fibrosis in Fabry disease was associated with malignant ventricular arrhythmias (occurring in 27.1% of patients with fibrosis vs 0% without), and its annual increase independently predicted MVAs.