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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)?
Methods:
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).
Results:
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.
Conclusions:
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.
Perspective:
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, 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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