PO21 Impact of genetics on patients with non-ischemic dilated myocardiopathy included on elective cardiac transplant list

Abstract Introduction Dilated myocardiopathy (DCM) is one of the main indications for heart transplantation in Spain, particularly in young patients (1). Several studies have demonstrated that the genetic substrate influences the clinical course of non-ischemic dilated cardiomyopathy (DCM). However, its role in the prognosis of patients on elective list for heart transplantation (HT) has not been assessed. The aim of this study is to analyse the role of genetics in patients with DCM included in HT list on clinical events. Methods This is a single-center retrospective study of all patients older than 18 years, with a diagnose of DCM who were included in an elective list for HT between 2010 and 2024 and had undergone panel-based genetic testing (GT) that includes at least 30 genes. The data set included demographics, family history, signs, symptoms, and treatment at inclusion. Complementary tests including ECG, Holter ECG, echocardiography, as well as cardiac magnetic resonance. Genetic testing was performed at an accredited genetic laboratory. Genetic variant interpretation was centrally curated following American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Genetic testing was considered positive if a pathogenic or likely pathogenic variant was identified. Follow-up started at the time of inclusion in heart transplantation waiting list and finished at the time of heart transplantation or exclusion. Follow-up was censored at the time of exclusion from waiting list due to clinical improvement, medical complication that rules out heart transplant or death. A composite primary endpoint was defined as death, exclusion due to medical complication or upgrading to urgent or emergent waiting list. A composite secondary endpoint included death, exclusion due to medical complication, upgrading to urgent or emergent waiting list, heart failure decompensation requiring intravenous diuretic or malignant ventricular arrhythmia (MVA) defined as a sudden cardiac death (SCD), sustained ventricular tachycardia (VT) or appropriate ICD therapy. Results A total of 36 patients were included (age 50.5 ± 11.8 years, 72.2% male); 14 patients (38%) were gene-positive (Table 1). The more frequent genes were LMNA (35.7%) and TTN (21.4%). The gene-positive group had a higher prevalence of family history of sudden cardiac death (50% vs. 4.6%; P = 0.003). The overall median follow-up was 4.0 months (IQR: 1.1–8.8). During follow-up, 4 patients (11.1%) reached the primary endpoint 2 gene-positive (14.3%) and 2 gene-negative (9.1%), all due to upgrade to urgent or emergent listing. No statistically significant differences were observed between groups (Hazard ratio HR gene-positive: 1.91; 95% CI: 0.24–15.0; p = 0.54). Seventeen patients (47.2%) experienced the secondary endpoint 8 gene-positive (57.1%) and 9 gene-negative (40.9%), with no statistically significant differences (HR gene-positive: 1.87; 95% CI: 0.69–5.12; p= 0.22). Conclusions No significant differences were observed in the clinical course of patients with NIDCM electively listed for HT according to genetic status. These findings suggest that genetics may not play a major role once advanced stages of the disease have been reached