P6328
Outcomes of dilated cardiomyopathy in Lamin A/C mutation carriers

Background: Mutations in Lamin A/C gene (LMNA) usually cause cardiac phenotypes, including dilated cardiomyopathy (DCM), cardiac conduction disturbance, atrial fibrillation, and malignant ventricular tachyarrhythmias (mVTAs). Type of LMNA related DCM have been reported to be associated with susceptibility to mVTAs.

Objectives: The purpose of this study was to assess of the adverse arrhythmic and non-arrhythmic outcomes of DCM in LMNA mutation carriers.

Methods: The study included 147 DCM patients (98 / 66,6% male, NYHA 2,47±0,45, LVEF 33,4±9.12%, follow-up was at least a median 39 months). The mean age of patients when they underwent genetic testing (cardiopanel Illumina Inc, US) was 40,3±18,6 years.

Results: Pathogenic mutations were detected in 56 (38,1%) patients (pts). Seventeen pts (11,5%) had LMNA mutations (missense, splicing) and 39 pts had gene mutation causing a disease that was identified in other genes (TTN, MYH7, ACTC1, MYH6, SCN5A, DES, SCN1B ACTN2, CRYAB, BAG3, LDB3, MYBPC3, ILK, NEXN, MYPN). We compared clinical data from DCM pts such as LMNA mutation carriers (n=17) to other gene mutations carriers (n=39), and subjects who had negative genetic test (idiopathic DCM; n=91). LMNA carriers presented with DCM at earlier age than gene-mutation negative subjects (probands 33,9 vs 46,7 years, p=0.003), more often developed LVEF <35% (HR 1.43, p=0.01), and had earlier age of death (probands 39,7 vs. 59,3 years, p<0.01). LMNA positive probands had the worst composite outcomes (mVTA, heart transplantation or LVAD, HF death, SCD) of DCM (HR 1.59, p<0.01) than idiopathic DCM pts and other gene-positive subjects (HR 0.58, p=0.07). It was found that LMNA mutations determine the risk of early onset of cardiac conduction abnormalities, estimated using ROC analysis (AUC 0,786, p<0.01). Kaplan-Meier analysis with survival curve showed a worse prognosis for DCM-causing mutations gene carriers (LMNA et gene al., n=56) in comparison to non-carriers (n=91) with idiopathic DCM (p=0.027, log-rank test = -2.16).

Conclusions: LMNA-related DCM is associated with a high incidence of phenotypic progression and adverse arrhythmic and non-arrhythmic events. LMNA positive pts had an earlier occurrence of cardiac conduction disturbance. The poor prognosis of LMNA-related DCM, suggest that genetic analysis might be useful for diagnosis and risk stratification.