Varying Phenotypes and Outcomes in LMNA Cardiomyopathy

Abstract

<h3>Purpose</h3> The LMNA cardiomyopathies are caused by mutations in the Lamin A/C gene that can cause varying phenotypes. The purpose of this study was to characterize differences in outcomes between dilated and non-dilated patients with LMNA cardiomyopathy. <h3>Methods</h3> We performed a retrospective analysis of patients who received a genetic cardiomyopathy panel from 2017-2021 and were found to have a LMNA mutation. Dilated phenotype was defined as left ventricular end diastolic diameter >5.8cm in males and >5.2cm in females. Kaplan Meier analysis using birth as the reference point was used to compare age of advanced therapies between the groups. <h3>Results</h3> A total of 20 patients were found to have LMNA mutations, 6 dilated, 14 nondilated. Age of diagnosis was younger in the dilated phenotype. There were no other differences in demographics or comorbid conditions between the groups. LVEF was lower in the dilated group. While was no difference in AICD placement between groups, incidence of advanced therapies, defined as either LVAD or heart transplant, was higher in the dilated group (Table 1). Patients with the dilated phenotype required advanced therapies at an earlier age. (Figure 1). There was 1 death at the age of 67 in the non-dilated group. There was no difference in mutation significance between groups, with 25% of all LMNA mutations in this group being a variant of unknown significance. All except 1 of the mutations were substitutions. <h3>Conclusion</h3> Although incidence of comorbid conditions and arrhythmias are similar between groups, the dilated phenotype has a more severe disease course, presenting and requiring advanced therapies at a younger age compared to the non-dilated phenotype.