Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease.

Abstract

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.

• Authors: Johannes Krämer, Markus Niemann, Stefan Störk, Stefan Frantz, Meinrad Beer, Georg Ertl, Christoph Wanner, Frank Weidemann
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 114 Issue 6 Pg. 895-900 (Sep 15 2014) ISSN: 1879-1913 [Electronic] United States
• PMID: 25073565 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Collagen

Topics

• Adult
• Biomarkers (blood)
• Cardiomyopathies (diagnosis, epidemiology, etiology)
• Collagen (blood)
• Disease Progression
• Electrocardiography, Ambulatory
• Fabry Disease (blood, complications, diagnosis)
• Female
• Fibrosis (diagnosis, epidemiology, etiology)
• Follow-Up Studies
• Germany (epidemiology)
• Humans
• Magnetic Resonance Imaging, Cine
• Male
• Myocardium (pathology)
• Prospective Studies
• Survival Rate (trends)
• Tachycardia, Ventricular (diagnosis, epidemiology, etiology)
• Time Factors