Genotype-Driven Prognostication in Dilated Cardiomyopathy

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.

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.

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).

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.