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ABSTRACT: Background
Alcoholic 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.Objectives
This 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.Methods
The 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.Results
Variants 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.Conclusions
TTNtv 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.
SUBMITTER: Ware JS
PROVIDER: S-EPMC5957753 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Ware James S JS Amor-Salamanca Almudena A Tayal Upasana U Govind Risha R Serrano Isabel I Salazar-Mendiguchía Joel J García-Pinilla Jose Manuel JM Pascual-Figal Domingo A DA Nuñez Julio J Guzzo-Merello Gonzalo G Gonzalez-Vioque Emiliano E Bardaji Alfredo A Manito Nicolas N López-Garrido Miguel A MA Padron-Barthe Laura L Edwards Elizabeth E Whiffin Nicola N Walsh Roddy R Buchan Rachel J RJ Midwinter William W Wilk Alicja A Prasad Sanjay S Pantazis Antonis A Baski John J O'Regan Declan P DP Alonso-Pulpon Luis L Cook Stuart A SA Lara-Pezzi Enrique E Barton Paul J PJ Garcia-Pavia Pablo P
Journal of the American College of Cardiology 20180501 20
<h4>Background</h4>Alcoholic 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.<h4>Objectives</h4>This 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.<h4>Methods</h4>The authors chara ...[more]