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Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis.

ABSTRACT: Aims:We used contrast-enhanced cardiac magnetic resonance (CMR) to evaluate differences in myocardial fibrosis measured at the year-10 examination between participants with and without cardiovascular (CV) events accrued in a large population based study over the preceding 10-year follow-up period in this retrospective study. Methods and results:The MESA study enrolled 6814 participants free of CV disease at baseline (2000-2002). We included MESA participants who underwent contrast-enhanced CMR at the MESA year-10 exam (N?=?1840). We defined a composite CV endpoint of coronary heart disease, heart failure, atrial fibrillation, stroke, and peripheral artery disease. Using CMR, we characterized myocardial fibrosis with late-gadolinium enhancement for scar and T1 mapping indices of diffuse fibrosis. Demographic and CV-risk adjusted logistic (presence of scar) and linear regression (pre-contrast T1, T1 at 12 and 25?min post-contrast, and extracellular volume fraction or ECV) models were used to assess the relationship between fibrosis and events. The mean values of T1 indices were-pre-contrast T1: 977?±?45?ms; T1 at 12': 456?±?40?ms; T1 at 25': 519?±?41?ms; ECV: 27.1?±?3.2%. One-hundred and forty-six (7.9%) participants had myocardial scar. The presence of scar was strongly associated with prior CV events (adjusted coeff: 1.36, P?

SUBMITTER: Ambale-Venkatesh B

PROVIDER: S-EPMC6343084 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis.

Ambale-Venkatesh Bharath B Liu Chia-Ying CY Liu Yuan-Chang YC Donekal Sirisha S Ohyama Yoshiaki Y Sharma Ravi K RK Wu Colin O CO Post Wendy S WS Hundley Gregory W GW Bluemke David A DA Lima João A C JAC

European heart journal. Cardiovascular Imaging 20190201 2

<h4>Aims</h4>We used contrast-enhanced cardiac magnetic resonance (CMR) to evaluate differences in myocardial fibrosis measured at the year-10 examination between participants with and without cardiovascular (CV) events accrued in a large population based study over the preceding 10-year follow-up period in this retrospective study.<h4>Methods and results</h4>The MESA study enrolled 6814 participants free of CV disease at baseline (2000-2002). We included MESA participants who underwent contrast ...[more]

PMID: 30325426

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Project description:BackgroundRare pathogenic variants in cardiomyopathy (CM) genes can predispose to cardiac remodeling or fibrosis. We studied the carrier status for such variants in adults without clinical cardiovascular disease (CVD) in whom cardiac MRI (CMR)-derived measures of myocardial fibrosis were obtained in the Multi-Ethnic Study of Atherosclerosis (MESA).ObjectivesTo identify CM-associated pathogenic variants and assess their relative prevalence in participants with extensive myocardial fibrosis by CMR.MethodsMESA whole-genome sequencing data was evaluated to capture variants in CM-associated genes (n = 82). Coding variants with a frequency of <0.1% in gnomAD and 1,000 Genomes Project databases and damaging/deleterious effects based on in-silico scoring tools were assessed by ClinVar database and ACMG curation guidelines for evidence of pathogenicity. Cases were participants with high myocardial fibrosis defined as highest quartile of extracellular volume (ECV) or native T1 time in T1-mapping CMR and controls were the remainder of participants.ResultsA total of 1,135 MESA participants had available genetic data and phenotypic measures and were free of clinical CVD at the time of CMR. We identified 6,349 rare variants in CM-associated genes in the overall MESA population, of which six pathogenic/likely pathogenic (P/LP) variants were present in the phenotyped subpopulation. The genes harboring P/LP variants in the case group were MYH7, CRYAB, and SCN5A. The prevalence of P/LP rare variants in cases was higher than controls (5 in 420 [1.1%] vs. 1 in 715 [0.1%], p = 0.03). We identified two MYBPC3 Variants of Unknown Significance (VUS)s with borderline pathogenicity in the case group. The left ventricle (LV) volume, mass, ejection fraction (EF), and longitudinal and circumferential strain in participants with the variants were not different compared to the overall cohort.ConclusionsWe observed a higher prevalence of rare potentially pathogenic CM associated genetic variants in participants with significant myocardial fibrosis quantified in CMR as compared to controls without significant fibrosis. No cardiac structural or functional differences were found between participants with or without P/LP variants.

Dataset Information

Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis.

Publications

Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis.

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