Genotype-Driven Prognostication in Dilated Cardiomyopathy

BACKGROUND AND OBJECTIVES: Dilated cardiomyopathy (DCM) has a variable prognosis and generally poor outcomes. Genetic testing could identify high-risk patients. This study aimed to evaluate the prognostic impact of genetic testing in patients with DCM. METHODS: This retrospective study included consecutive patients with DCM who underwent targeted panel sequencing or whole genome sequencing at Samsung Medical Center from 2018 to 2023. Patients were divided into genotype-positive and genotype-negative groups based on the presence of pathogenic or likely pathogenic variants. The primary outcome was a composite of cardiac death, heart transplantation, and left ventricular assist device implantation at 5 years. The primary outcome was compared according to the results of genetic testing. RESULTS: In total, 239 patients were analyzed and followed for a median of 2.6 years. Among the patients, 79 (33.1%) were genotype-positive, and 160 (66.9%) were genotype-negative. The genotype-positive group had a significantly higher risk of the primary outcome than the genotype-negative group (hazard ratio, 1.80; confidence interval, 1.10-2.95; p=0.020). Further dividing genotype-negative patients based on the presence of a variant of uncertain significance (VUS) revealed a stepwise increase in the incidence of the primary outcome among the 3 groups (no variant 22.3%, VUS 43.9%, genotype-positive 42.9%; overall log-rank p=0.032). Also, the incidence of the primary outcome differed significantly in genotype-positive patients according to the affected functional gene group (overall log-rank p=0.003). CONCLUSIONS: Patients with DCM exhibited varying prognoses according to genotype. Further research is needed to refine risk stratification and the clinical application of genetic testing in DCM.