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Myocardial Storage, Inflammation, and Cardiac Phenotype in Fabry Disease After One Year of Enzyme Replacement Therapy

Nordin, S; Kozor, R; Vijapurapu, R; Augusto, JB; Knott, KD; Captur, G; Treibel, TA; ... Moon, JC; + view all (2019) Myocardial Storage, Inflammation, and Cardiac Phenotype in Fabry Disease After One Year of Enzyme Replacement Therapy. Circulation: Cardiovascular Imaging , 12 (12) , Article e009430. 10.1161/CIRCIMAGING.119.009430. Green open access

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Abstract

BACKGROUND: Cardiac response to enzyme replacement therapy (ERT) in Fabry disease is typically assessed by measuring left ventricular mass index using echocardiography or cardiovascular magnetic resonance, but neither quantifies myocardial biology. Low native T1 in Fabry disease represents sphingolipid accumulation; late gadolinium enhancement with high T2 and troponin elevation reflects inflammation. We evaluated the effect of ERT on myocardial storage, inflammation, and hypertrophy. METHODS: Twenty patients starting ERT (60% left ventricular hypertrophy–positive) were compared with 18 patients with early disease and 18 with advanced disease over 1 year at 3 centers. Cardiovascular magnetic resonance (left ventricular mass index, T1, T2, global longitudinal strain, and late gadolinium enhancement) and biomarkers (high-sensitive troponin-T and NT-proBNP [N-terminal Pro-B-type natriuretic peptide]) at baseline (pre-ERT) and 12 months were performed. Early disease controls were stable, treatment-naïve patients (mainly left ventricular hypertrophy–negative); advanced disease controls were stable, established ERT patients (mainly left ventricular hypertrophy–positive). RESULTS: Over 1 year, early disease controls increased maximum wall thickness and left ventricular mass index (9.8±2.7 versus 10.2±2.6 mm; P=0.010; 65±15 versus 67±16 g/m2; P=0.005) and native T1 fell (981±58 versus 959±61 ms; P=0.002). Advanced disease controls increased T2 in the late gadolinium enhancement area (57±6 versus 60±7 ms; P=0.023) with worsening global longitudinal strain (−13.2±3.4 versus −12.1±4.8; P=0.039). Newly treated patients had a small reduction in maximum wall thickness (14.8±5.9 versus 14.4±5.7 mm; P=0.028), stable left ventricular mass index (93±42 versus 92±40 g/m2; P=0.186) and a reduction in T1 lowering (917±49 versus 931±54 ms; P=0.017). CONCLUSIONS: Fabry myocardial phenotype development is different at different disease stages. After 1 year of ERT initiation, left ventricular hypertrophy–positive patients have a detectable, small reduction in left ventricular mass and storage.

Type: Article
Title: Myocardial Storage, Inflammation, and Cardiac Phenotype in Fabry Disease After One Year of Enzyme Replacement Therapy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCIMAGING.119.009430
Publisher version: https://doi.org/10.1161/CIRCIMAGING.119.009430
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution Non-CommercialNoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. https://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Fabry disease, inflammation, myocardium, sphingolipid, troponin
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10088190
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