title: 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: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Johannes
authors: J
authors: Krämer
authors: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Markus
authors: M
authors: Niemann
authors: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Stefan
authors: S
authors: Störk
authors: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Stefan
authors: S
authors: Frantz
authors: Institute of Radiology, University of Ulm, Ulm, Germany.
authors: Meinrad
authors: M
authors: Beer
authors: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Georg
authors: G
authors: Ertl
authors: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Christoph
authors: C
authors: Wanner
authors: Department of Internal Medicine I, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. Electronic address: weidemann_f@ukw.de.
authors: Frank
authors: F
authors: Weidemann
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D003094:Collagen / Q000097:blood; D018450:Disease Progression; D015716:Electrocardiography, Ambulatory; D000795:Fabry Disease / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D005260:Female; D005355:Fibrosis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009206:Myocardium / Q000473:pathology*; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003094:Collagen