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Gender‐specific differences in major cardiac events and mortality in lamin A/C mutation carriers
Author(s) -
Rijsingen Ingrid A.W.,
Nannenberg Eline A.,
Arbustini Eloisa,
Elliott Perry M.,
Mogensen Jens,
Hermansvan Ast Johanna F.,
Kooi Anneke J.,
Tintelen J. Peter,
Berg Maarten P.,
Grasso Maurizia,
Serio Alessandra,
Jenkins Sharon,
Rowland Camilla,
Richard Pascale,
Wilde Arthur A.M.,
Perrot Andreas,
Pankuweit Sabine,
Zwinderman Aeilko H.,
Charron Philippe,
Christiaans Imke,
Pinto Yigal M.
Publication year - 2013
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfs191
Subject(s) - lmna , medicine , penetrance , cardiology , heart failure , dilated cardiomyopathy , sudden cardiac death , hazard ratio , cardiomyopathy , ejection fraction , cohort , lamin , confidence interval , genetics , phenotype , nucleus , psychiatry , biology , gene
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.