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BackgroundAlcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol.ObjectivesThis study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity.MethodsThe authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM.ResultsVariants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10-5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: -2.3% to -15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients.ConclusionsTTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.

Original publication

DOI

10.1016/j.jacc.2018.03.462

Type

Journal article

Journal

Journal of the American College of Cardiology

Publication Date

05/2018

Volume

71

Pages

2293 - 2302

Addresses

National Heart and Lung Institute, Imperial College London, London, United Kingdom; Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust London, London, United Kingdom; MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom.

Keywords

Humans, Cardiomyopathy, Alcoholic, Genetic Predisposition to Disease, Cohort Studies, Prospective Studies, Adult, Aged, Middle Aged, Female, Male, Self Report, Cardiotoxicity