Heart failure & cardiomyopathies
Clinical characteristics and prognostic impact of multiple pathogenic variants across the genetic spectrum of arrhythmogenic and dilated cardiomyopathies
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
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)
Single-variant
- Major arrhythmic events (MAE)
- 20%
- End-stage heart failure (ESHF)
- 9%
>1 P/LP variants in ≥1 ALVC/DCM gene
- MAE
- 48%
- ESHF
- 29%
>1 P/LP variants in >1 ARVC gene
- MAE
- 50%
- ESHF
- 17%
Major arrhythmic events (MAE)
Single-variant20%
>1 P/LP variants in ≥1 ALVC/DCM gene48%
>1 P/LP variants in >1 ARVC gene50%
End-stage heart failure (ESHF)
Single-variant9%
>1 P/LP variants in ≥1 ALVC/DCM gene29%
>1 P/LP variants in >1 ARVC gene17%
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.
Summarised from the published abstract; every number is checked against it