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

Eur J Heart Fail. 2013 Apr;15(4):376-84. doi: 10.1093/eurjhf/hfs191. Epub 2012 Nov 25.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / mortality
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / mortality*
  • Cohort Studies
  • Female
  • Heart Failure / genetics
  • Heart Failure / mortality
  • Heterozygote*
  • Humans
  • Lamin Type A / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Prevalence
  • Retrospective Studies
  • Sex Factors


  • LMNA protein, human
  • Lamin Type A