Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study.
Adult
Aged
Biomarkers
/ blood
Cardiomyopathies
/ diagnostic imaging
Disease Progression
Early Diagnosis
Fabry Disease
/ complications
Female
Fibrosis
Gadolinium
/ chemistry
Heart
/ diagnostic imaging
Humans
Hypertrophy, Left Ventricular
/ etiology
Magnetic Resonance Imaging
Male
Middle Aged
Myocardium
/ pathology
Ventricular Dysfunction, Left
/ etiology
Biomarker
Cardiac magnetic resonance imaging
Fabry disease late gadolinium enhancement Myocardial fibrosis Proteomics
Journal
Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
15
06
2018
revised:
09
11
2018
accepted:
09
11
2018
pubmed:
31
12
2018
medline:
9
8
2019
entrez:
31
12
2018
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 30594474
pii: S1096-7192(18)30360-3
doi: 10.1016/j.ymgme.2018.11.005
pii:
doi:
Substances chimiques
Biomarkers
0
Gadolinium
AU0V1LM3JT
Banques de données
ClinicalTrials.gov
['NCT01210196']
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Pagination
169-182Informations de copyright
Copyright © 2019 Shire International GmbH, The Authors. Published by Elsevier Inc. All rights reserved.