Heart failure & cardiomyopathiesResearch article
Clinical characteristics and prognostic impact of multiple pathogenic variants across the genetic spectrum of arrhythmogenic and dilated cardiomyopathies
- retrospectively analyzed
Authors' conclusion
Multiple P/LP variants confer an increased risk of arrhythmic events and heart failure across the ACM/DCM spectrum.
Study context
- Population
- Genotype-positive patients with ≥1 P/LP variant in a definitive or strong evidence arrhythmogenic right ventricular cardiomyopathy (ARVC)- or arrhythmogenic left ventricular cardiomyopathy (ALVC)/DCM-causative gene27 (3%) harbored >1 P/LP variants
- Participants
- 1,054 patients
- Comparison
- single vs multiple P/LP variants
- >1 P/LP variants in ≥1 ALVC/DCM genen = 21
- >1 P/LP variants in >1 ARVC genen = 6
- Outcome
- MAE (sustained ventricular tachycardia, ventricular fibrillation, aborted cardiac arrest, appropriate implantable cardioverter-defibrillator therapy, and sudden cardiac death) and ESHF (transplant or heart failure death)
Main finding
As reported in the abstract
single-variant
20%
Major arrhythmic events (MAE) · end-stage heart failure (ESHF) 9%
>1 P/LP variants in ≥1 ALVC/DCM gene
48%
MAE · ESHF 29%
>1 P/LP variants in >1 ARVC gene
50%
MAE · ESHF 17%
Each group vs single-variantHazard ratio (CI)P value
>1 P/LP variants in ≥1 ALVC/DCM geneMAE, adjusted
2.46(1.28–4.72)
P = 0.01>1 P/LP variants in ≥1 ALVC/DCM geneESHF, adjusted
3.15(1.35–7.37)
P = 0.01>1 P/LP variants in >1 ARVC geneMAE, adjusted
2.67(1.28–8.72)
P = 0.03Original publication
Clinical characteristics and prognostic impact of multiple pathogenic variants across the genetic spectrum of arrhythmogenic and dilated cardiomyopathies. Heart Rhythm. Published 11 August 2026. doi:10.1016/j.hrthm.2026.07.051
Summarised from the published abstract; every number is checked against it