Genetics and Prognosis in Patients With Dilated Cardiomyopathy

Quick Takes

  • Patients with pathogenic or likely pathogenic variants had a worse clinical outcome than their genotype-negative peers.
  • Genetic testing identifies patients at higher risk of malignant ventricular arrhythmias and end-stage heart failure when LVEF is ≤35%, and that clinical course varies depending on the affected gene.
  • The next step would be to determine the value of these findings at the point-of-care setting.

Study Questions:

What is the clinical impact of genotype findings on prognosis in patients with nonischemic dilated cardiomyopathy (DCM)?


The study cohort was comprised of 1,005 genotyped DCM probands. Baseline and longitudinal clinical data were retrospectively collected from this cohort. 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 remodeling (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 authors of this study concluded that DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course varied depending on the underlying affected gene.


This is an important study because its findings suggest that genetic studies will allow us to better identify patients with DCM with a worse prognosis. These findings now need to be evaluated for their efficacy as a point-of-care tool.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Arrhythmias, Cardiac, Cardiomyopathies, Cardiomyopathy, Dilated, Genotype, Geriatrics, Heart Failure, Point-of-Care Systems, Secondary Prevention, Stroke Volume, Ventricular Remodeling

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