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Gender-specific differences in major cardiac events and mortality in lamin A/C mutation carriers

Item Type:Article
Title:Gender-specific differences in major cardiac events and mortality in lamin A/C mutation carriers
Creators Name:van Rijsingen, I.A.W. and Nannenberg, E.A. and Arbustini, E. and Elliott, P.M. and Mogensen, J. and Hermans-van Ast, J.F. and van der Kooi, A.J. and van Tintelen, J.P. and van den Berg, M.P. and Grasso, M. and Serio, A. and Jenkins, S. and Rowland, C. and Richard, P. and Wilde, A.A.M. and Perrot, A. and Pankuweit, S. and Zwinderman, A.H. and Charron, P. and Christiaans, I. and Pinto, Y.M.
Abstract:AIMS: Mutations in the lamin A/C gene (LMNA) cause a variety of clinical phenotypes, including dilated cardiomyopathy. LMNA is one of the most prevalent mutated genes in dilated cardiomyopathy, and is associated with a high risk of arrhythmias, sudden cardiac death, and heart failure. There are few data on the impact of age and gender on cardiac disease penetrance and mortality. METHODS AND RESULTS: In a multicentre cohort of 269 LMNA mutation carriers, we evaluated gender-specific penetrance of cardiac involvement and major cardiac events. All-cause mortality of mutation carriers [standardized mortality ratio (SMR)] was determined. Cardiac disease penetrance was age dependent and almost complete at the age of 70 years. The presence of an LVEF </=45% was significantly higher in men (P < 0.001). However, there was no difference between genders in the prevalence of atrioventricular block, atrial tachyarrhythmias, and non-sustained ventricular tachycardia. Malignant ventricular arrhythmias (26% vs. 8%) and end-stage heart failure (28% vs. 14%) were more common in men than in women (P < 0.001 and P = 0.006, respectively). All-cause mortality of mutation carriers was significantly increased [SMR 4.0, 95% confidence interval (CI) 2.8-5.2] between the ages of 15 and 75 years. Mortality in men was higher than in women (hazard ratio 2.2, 95% CI 1.2-4.3). CONCLUSIONS: This large cohort of LMNA mutation carriers demonstrates a high cardiac disease penetrance and a high mortality in mutation carriers. Male mutation carriers have a worse prognosis due to a higher prevalence of malignant ventricular arrhythmias and end-stage heart failure.
Keywords:Lamin A/C, Gender, Mortality, Cardiomyopathy, Penetrance
Source:European Journal of Heart Failure
Page Range:376-384
Date:April 2013
Official Publication:https://doi.org/10.1093/eurjhf/hfs191
PubMed:View item in PubMed

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