Gender‐specific differences in major cardiac events and mortality in lamin A/C mutation carriers. (April 2013)

• Record Type: Journal Article
• Authors: van, Ingrid A.W.; Nannenberg, Eline A.; Arbustini, Eloisa; Elliott, Perry M.; Mogensen, Jens; Hermans‐van Ast, Johanna F.; van der, Anneke J.; van, J. Peter; van den, 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.
• Is Part Of: European journal of heart failure. Volume 15:Number 4(2013)
• Page Start: 376
• Page End: 384
• Publication Date: 2013-04
• Subjects: Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1093/eurjhf/hfs191
• Languages: English
• ISSNs: 1388-9842

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ejhfhfs191-sec-0001" sec-type="section"> <title>Aims</title> <p>Mutations in the lamin A/C gene (<italic>LMNA</italic>) cause a variety of clinical phenotypes, including dilated cardiomyopathy. <italic>LMNA</italic> 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.</p> </sec> <sec id="ejhfhfs191-sec-0002" sec-type="section"> <title>Methods and results</title> <p>In a multicentre cohort of 269 <italic>LMNA</italic> 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 (<italic>P</italic> < 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 (<italic>P</italic> < 0.001 and <italic>P</italic> = 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).</p> </sec> <sec id="ejhfhfs191-sec-0003" sec-type="section"> <title>Conclusions</title> <p>This large cohort of <italic>LMNA</italic> 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.</p> </sec> </abstract>