P3516Sex differences in cardiac function and muscular dystrophy in lamin A/C genotype positive family members

Abstract

Abstract Background Lamin A/C dilated cardiomyopathy is a highly penetrant inheritable cardiomyopathy with some patients developing muscluar dystrophy. Studies have indicated higher morbidity and mortality in men compared to women with lamin A/C. Purpose To explore sex differences in cardiac function, arrhythmias and muscular dystrophy in lamin A/C genotype positive family members of lamin A/C probands. Methods We included consecutive lamin A/C genotype positive family members recruited for cardiological evalutation based on the identification of lamin A/C genotype by cascade genetic screening. Cardiac function was assessed by echocardiography. Impaired cardiac function was defined according to guidelines as left ventricular ejection fraction (LVEF) <52% in men, <54% in women. Presence of AV-block, atrial fibrillation and ventricular arrhythmias were evaluated by12-lead ECG, Holter monitoring, and interrogation of cardiac implantable electronic devices. Presence of muscular dystrophy was assessed retrospectively from medical records, and defined as present or not based on description of typical symptoms and/or findings on neurological exam. Results We included 55 lamin A/C genotype positive family members (age 35±15 years, 49% female). Men were younger at time of evaluation (31±15 years vs. 40±14 years, p=0.047). Despite lower age, men had significantly lower LVEF (48±12% vs. 55±9%, p=0.016) (Figure left panel), and showed worse survival free from impaired cardiac function compared to women (log rank p=0.019) (Figure, mid panel). Male sex was a marker for impaired cardiac function when adjusted for age (adjusted OR 5.3 [95% CI; 1.5–18.8]). Women had higher prevalence of muscular dystrophy compared to men (35% vs. 0%, p=0.004) (Figure right panel). We observed no sex related differences for AV-block, atrial fibrillation, nor ventricular arrhythmias. Conclusions Male lamin A/C genotype family members had earlier penetrance and more frequently impaired cardiac function compared to women. AV-block and arrhythmic disease did not differ. Muscular dystrophy was more frequent in women. These findings indicate sex differences in the phenotypical expression of lamin A/C disease.