Role of genetics in the prognostic stratification of patients with Dilated Cardiomyopathy

Abstract

Dilated cardiomyopathy (DCM) is a disease with an increasingly recognized role of genetic background. However, the role of genetic variants on the prognosis of patients with DCM is still poorly understood. This retrospective study investigated the prognostic role of genetic variants in a cohort of independent DCM patients, excluding patients with a pathogenic variant on the LMNA gene. 162 DCM index case patients were analyzed by next-generation sequencing using a panel of (at least) 51 genes involved in the disease. The following composite outcome measures were assessed severe ventricular arrhythmia (sustained tachycardia or fibrillation) or sudden death, and advanced heart failure defined by a heart failure death, heart transplantation or destination therapy left ventricular assist device implantation. We identified pathogenic variants in 50% patients in 22 genes; the most frequently involved genes were Titin (21% of variants), DSP (10%) and RMB20 (10%). Patients mutation carrier, as compared to non-carrier, had more frequently advanced heart failure (28% versus 9%, P < 0.01) without difference to severe ventricular arrhythmia (16% versus 13%, P = 0.5). In mutation carrier, Non-Motor Sarcomerics Genes had more advanced heart failure compared to Motor Sarcomeris genes and non-carrier ( P < 0.01). DCM patients who are mutation carrier are associated with more hemodynamic events than non-carrier. Genetic background may therefore be useful for prognostic stratification and management of DCM patients.