Relation of Burden of Myocardial Fibrosis to Malignant Ventricular Arrhythmias and Outcomes in Fabry Disease

• Published in: The American journal of cardiology Vol. 114; no. 6; pp. 895 - 900
• Main Authors: Krämer, Johannes, MD, Niemann, Markus, MD, Störk, Stefan, MD, PhD, Frantz, Stefan, MD, Beer, Meinrad, MD, Ertl, Georg, MD, Wanner, Christoph, MD, Weidemann, Frank, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2014; Elsevier Limited
• Subjects: Adult; Biomarkers - blood; Blood pressure; Cardiomyopathies - diagnosis; Cardiomyopathies - epidemiology; Cardiomyopathies - etiology; Cardiovascular; Collagen; Collagen - blood; Disease Progression; Electrocardiography, Ambulatory; Enzymes; Fabry Disease - blood; Fabry Disease - complications; Fabry Disease - diagnosis; Female; Fibrosis - diagnosis; Fibrosis - epidemiology; Fibrosis - etiology; Follow-Up Studies; Germany - epidemiology; Heart attacks; Humans; Magnetic Resonance Imaging, Cine; Male; Medical prognosis; Myocardium - pathology; Prospective Studies; Studies; Survival Rate - trends; Tachycardia, Ventricular - diagnosis; Tachycardia, Ventricular - epidemiology; Tachycardia, Ventricular - etiology; Time Factors; Germany
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2014.06.019

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.