Arrhythmic phenotypes in patients with left ventricular non-compaction cardiomyopathy

Abstract

Abstract Background Identification of pts with left ventricular non-compaction cardiomyopathy (NCCM) at high risk of life-threatening arrhythmic events is focused on clinical and instrumental criteria. The genetic component is not taken into account when deciding on a strategy for preventive measures. Purpose To analyze life-threatening arrhythmic events in pts with the arrhythmic variant of NCCM and to identify genetic factors that may increase the risk of life-threatening arrhythmic events. Methods The study included 159 pts, among whom 58 had malignant ventricular arrhythmias (mean age 43.54±11.95 years, 34/24/58.6% male). The NCCM criteria were confirmed using Echocardiography and CMR. Mutation search was carried out by the next generation sequencing (NGS) in 21 pts with nonsustained ventricular tachycardia (NVT). Results During the follow-up period (median follow-up of 36 months), life-threatening arrhythmic events (documented sustained VT, SCD with successful resuscitation and CD implantation, SCD) were registered in 29 pts (50%), and 10 pts had CD implanted. As a result of sequencing, 23.8% (5 out of 21) of pts with NVT revealed rare genetic variants with uncertain clinical significance (VUS) in 3 genes encoding ion channel proteins: KCNQ1, KCNH2 (9.5%), RYR2 (9.5%). In 9 (42.9%) pts, 10 identified mutations were localized in the genes responsible for the synthesis of sarcomeric proteins: MYBPC3 (23.8%), MYH7 (23.8%). 12 genetic variants were found in overlapping phenotypes between NCCM, ARVC and DCM: PKP2, DSP, PLN, TRPM4 (14.3%), RBM20, LDB3 (9.5%), DPP6, DTNA, NEXN in 11 (52.4%) pts. In this group of pts, the most common (81.8% of cases) were life-threatening arrhythmic events that required surgical intervention: 6 pts were implanted with CD for primary prevention of SCD, two pts - CRT-D, two pts with systolic dysfunction were performed with OHT and one patient was implanted with the Accucinch transcatheter direct mitral valve annuloplasty system. In pts with mutations in sarcomeric protein genes, CD was implanted in 4.7% of cases, and in 14.3% of pts with mutations in ion channel genes (p<0.01). Conclusion The presence of mutations in genes that control the functioning of ion channels in complex overlapping genotypes is an additional risk factor for ventricular arrhythmias in patients with NCCM. Determining the genetic component opens up new opportunities for personalizing the risk stratification of pts with NCCM. Funding Acknowledgement Type of funding source: None