The study describes clinical impact of genotype findings on prognosis in patients with non-ischemic dilated cardiomyopathy (DCM).

The cohort study comprised of 1,005 genotyped DCM probands. Retrospective collection of baseline and longitudinal clinical data from the study. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events (MACE). Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodelling (LVRR).

The primary endpoint occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.17-1.94; p = 0.001), after a median follow-up of 4.04 years (interquartile range, 1.70-7.50 years). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR, 1.67; 95% CI, 1.16-2.41; p = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR, 1.50; 95% CI, 1.09-2.07; p = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (p = 0.047). Genotype-positive patients with baseline LV ejection fraction (LVEF) ≤35% had a higher incidence of MACE (HR, 1.62; 95% CI, 1.22-2.14; p = 0.001), ESHF (HR, 1.68; 95% CI, 1.13-2.48; p = 0.010), and MVA (HR, 1.58; 95% CI, 1.09-2.28; p = 0.015) than did genotype-negative patients with LVEF >35%. By contrast, outcomes in genotype-positive and genotype-negative patients with LVEF ≤35% were not statistically different. LVRR and clinical outcomes varied depending on the underlying affected gene.

The study concluded that worse prognosis is observed in DCM patients with pathogenic or likely pathogenic variants than genotype-negative individuals. Clinical course varied depending on the underlying affected gene. The study findings suggest that genetic studies will allow to better identify patients with DCM with a worse prognosis. 



Disease Condition ,Pathophysiology ,Myocardial Disease and Cardiomyopathies,Genetics and Molecular biology,Dilated Cardiomyopathy,Genetic Variation