Real-World Genetic Characteristics of Candidates for Implantable Cardioverter-Defibrillators with Dilated Cardiomyopathy

BackgroundThe real-world prevalence of sudden cardiac death (SCD)-related gene mutations and their relationship with implantable cardioverter-defibrillator (ICD) implantation in dilated cardiomyopathy (DCM) has not been clearly investigated. MethodsThis study included patients with sporadic DCM with persistent left ventricular ejection fraction (LVEF) [&le;] 35% even after 3 months of guideline-directed medical treatment or those with an ICD for secondary prevention and LVEF < 50%. Genetic tests targeting 444 pan-cardiomyopathy genes (including 36 core DCM genes) were performed, along with the collection of clinical and electrophysiological information. ResultsA total of 105 patients were enrolled (median age, 65.0 [57.5-75.0] years), and 33 (31%) were women. The average LVEF was 27.4 {+/-} 5.9%, and 46 patients (44%) had ICD or cardiac resynchronization therapy with ICD (34 for primary prevention and 12 for secondary prevention purpose) at the time of enrollment. Fourteen patients (13%) had pathogenic (P) or likely pathogenic (LP) variants (comprising 6 TTN, 4 DSP, 2 TNNT2, 1 RBM20, 1 DSG and 1 MYBPC3, one patients had both DSP and RBM20), and 59 patients (56%) had P/LP/variant of uncertain significance (VUS) in the 36 core DCM genes. Twenty-eight patients (27%) harbored SCD-related gene variants (14 DSP, 11FLNC, 9 RBM20 and 2 TMEM43). The prevalence of SCD gene variants tended to be higher in the secondary prevention and non-ICD groups (33.3% for secondary purposes, 11.8% for primary purposes, and 33.8% for non-ICD; p = 0.058). ConclusionsIn patients with advanced heart failure and DCM, P/LP-validated DCM variants were not common in sporadic cases. However, when extended to VUS, approximately half of the patients had core DCM-related variants. The prevalence of SCD variants was not lower in the non-ICD group, thus suggesting a potential risk of fatal arrhythmia. (Trial registration: CRIS KCT0004913)