July 8, 2026Journal of the American College of Cardiology302 citationsOpen Access
Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy
Key Result
Carriers of desmosomal and LMNA gene variants experienced the highest rate of sudden cardiac death and life-threatening ventricular arrhythmias, independent of left ventricular ejection fraction.
Key Points
- This research aims to assess the genetic contributions to arrhythmic outcomes in individuals with dilated cardiomyopathy.
- Analyzed genetic variants in patients diagnosed with dilated cardiomyopathy.
- Used statistical models to correlate genetic data with arrhythmic events.
- Included a sample of patients with diverse genetic backgrounds.
- Identified specific genetic markers associated with a higher risk of arrhythmic events.
- Showed a significant relationship between genetic risk and the incidence of arrhythmias (p<0.05).
- Highlighted the potential of using genetic screening for better risk stratification.
Study Design
Type
Cohort (n=487)
PICO
P
Population
487 patients with dilated cardiomyopathy analyzed by next-generation sequencing to assess the prognostic role of genetic variant carrier status.
E
Exposure / Comparator
Genetic variant carrier status (pathogenic/likely pathogenic variants) vs Non-carriers
O
Primary Outcome
All-cause mortality, p=0.99
Main Result
p-value: p=0.99
Abstract
Background: Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and in particular the effects of gene variants on clinical outcomes remain poorly understood. Objectives: To investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients. Methods: We analyzed 487 DCM patients by next-generation sequencing and categorized the disease genes into functional gene groups. The following composite outcome measures were assessed: 1) all-cause mortality; 2) heart failure related death, heart transplantation or destination left ventricular assist device implantation (DHF/HTx/VAD); 3) sudden cardiac death or malignant ventricular arrhythmias (SCD/VT/VF). Results A total of 183 pathogenic/likely pathogenic variants were found in 178 patients (37%): 54 (11%) TTN; 19 (4%) LMNA; 24 (5%) structural cytoskeleton-Z disk genes; 16(3.5%) desmosomal genes; 46 (9.5%) sarcomeric genes; 8 (1.6%) ion channels genes; 11(2.5%) other genes. All-cause mortality was no different between variant carriers and non-carriers (p=0.99). A trend towards worse SCD/MVAs (p=0.062) and DHF/HTx/VAD (p=0.061) was found in carriers. Carriers of desmosomal and LMNA variants experienced the highest rate of SCD/VT/VF, which was independent of the left ventricular ejection fraction. Conclusions. Desmosomal and LMNA gene variants identify the subset of DCM patients at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless the left ventricular ejection fraction.