Frank Weidemann1, Meinrad Beer2, Martina Kralewski3, Justyna Siwy4, Christoph Kampmann5. 1. Medizinische Klinik und Poliklinik I, University Hospital Würzburg, Würzburg, Germany; Klinikum Vest, Recklinghausen, Germany. Electronic address: frank.weidemann@klikum-vest.de. 2. Institut für Röntgendiagnostik, University Hospital Würzburg, Würzburg, Germany; Klinik für Diagnostische und Interventionelle Radiologie, University Hospital Ulm, Ulm, Germany. Electronic address: Meinrad.Beer@uniklinik-ulm.de. 3. Shire Deutschland GmbH, Berlin, Germany. Electronic address: MKralewski@shire.com. 4. Mosaiques Diagnostics GmbH, Hannover, Germany. Electronic address: siwy@mosaiques.de. 5. Zentrum für Kinder- und Jugendmedizin der Universitätsmedizin Mainz, Mainz, Germany. Electronic address: Kampmann@mail.uni-mainz.de.
Abstract
BACKGROUND: Initiation of enzyme replacement therapy (ERT) early in the Fabry disease course may facilitate better outcomes than in patients with advanced disease. Early diagnosis is often hindered by the heterogeneous nature of signs and symptoms, and by the presentation of atypical phenotypes. METHODS: The Sophisticated Assessment of Disease Burden in Patients with Fabry Disease study (SOPHIA; ClinicalTrials.gov, NCT01210196) evaluated clinical and diagnostic assessments for early detection of Fabry-related organ pathology in ERT-naïve patients with mild FD symptoms. Assessments included cardiac magnetic resonance imaging with late gadolinium enhancement (LGE-CMR), echocardiography, 24-h Holter electrocardiography, and biomarkers of FD and fibrosis. RESULTS: 35 patients with mean (SD) baseline age of 45.0 (10.2) years were included and assessed at baseline, 12 months, and (optionally) at 24 months. At baseline, LGE-CMR and elevated procollagen III N-terminal propeptide, sphingosine-1-phosphate, and globotriaosylsphingosine were the most prevalent indicators of early Fabry-related pathology. LGE was already present in 58.8% of patients with normal left ventricular mass index. 15.2% of patients showed grade 1 diastolic dysfunction. QRS duration increased from baseline to last observation, particularly in patients with severe baseline fibrosis. Fibrosis progressed from baseline to last observation, especially in patients with baseline LGE ≥ 2.50 mL (3.65 [1.14] mL vs 6.74 [1.10] mL). Statistically significant correlations were found between LGE volume and high-sensitivity troponin T, and between LGE volume and fragments of urinary collagen alpha-1 (I), (III), and (VII), and collagen alpha-3 (V). CONCLUSIONS: Fibrosis may become apparent before left ventricular hypertrophy occurs. LGE-CMR imaging is superior to conventional echocardiography for detecting early cardiomyopathy in FD and, in conjunction with biomarker tests, may help detect early organ involvement in mild FD.
BACKGROUND: Initiation of enzyme replacement therapy (ERT) early in the Fabry disease course may facilitate better outcomes than in patients with advanced disease. Early diagnosis is often hindered by the heterogeneous nature of signs and symptoms, and by the presentation of atypical phenotypes. METHODS: The Sophisticated Assessment of Disease Burden in Patients with Fabry Disease study (SOPHIA; ClinicalTrials.gov, NCT01210196) evaluated clinical and diagnostic assessments for early detection of Fabry-related organ pathology in ERT-naïve patients with mild FD symptoms. Assessments included cardiac magnetic resonance imaging with late gadolinium enhancement (LGE-CMR), echocardiography, 24-h Holter electrocardiography, and biomarkers of FD and fibrosis. RESULTS: 35 patients with mean (SD) baseline age of 45.0 (10.2) years were included and assessed at baseline, 12 months, and (optionally) at 24 months. At baseline, LGE-CMR and elevated procollagen III N-terminal propeptide, sphingosine-1-phosphate, and globotriaosylsphingosine were the most prevalent indicators of early Fabry-related pathology. LGE was already present in 58.8% of patients with normal left ventricular mass index. 15.2% of patients showed grade 1 diastolic dysfunction. QRS duration increased from baseline to last observation, particularly in patients with severe baseline fibrosis. Fibrosis progressed from baseline to last observation, especially in patients with baseline LGE ≥ 2.50 mL (3.65 [1.14] mL vs 6.74 [1.10] mL). Statistically significant correlations were found between LGE volume and high-sensitivity troponin T, and between LGE volume and fragments of urinary collagen alpha-1 (I), (III), and (VII), and collagen alpha-3 (V). CONCLUSIONS:Fibrosis may become apparent before left ventricular hypertrophy occurs. LGE-CMR imaging is superior to conventional echocardiography for detecting early cardiomyopathy in FD and, in conjunction with biomarker tests, may help detect early organ involvement in mild FD.
Authors: Derralynn A Hughes; Patricio Aguiar; Patrick B Deegan; Fatih Ezgu; Andrea Frustaci; Olivier Lidove; Aleš Linhart; Jean-Claude Lubanda; James C Moon; Kathleen Nicholls; Dau-Ming Niu; Albina Nowak; Uma Ramaswami; Ricardo Reisin; Paula Rozenfeld; Raphael Schiffmann; Einar Svarstad; Mark Thomas; Roser Torra; Bojan Vujkovac; David G Warnock; Michael L West; Jack Johnson; Mark J Rolfe; Sandro Feriozzi Journal: BMJ Open Date: 2020-10-10 Impact factor: 2.692
Authors: Roberta Esposito; Ciro Santoro; Giulia Elena Mandoli; Vittoria Cuomo; Regina Sorrentino; Lucia La Mura; Maria Concetta Pastore; Francesco Bandera; Flavio D'Ascenzi; Alessandro Malagoli; Giovanni Benfari; Antonello D'Andrea; Matteo Cameli Journal: J Clin Med Date: 2021-05-06 Impact factor: 4.241