Heart failure & cardiomyopathiesCohort study
Arrhythmic Risk in Carriers of Predicted Deleterious Rare Variants in Dilated and Arrhythmogenic Cardiomyopathy Genes
- cohort study using United Kingdom Biobank whole-exome sequencing data
- cause-specific Cox models accounting for competing risks
Authors' conclusion
PDrV carriers have a higher risk of severe cardiac events, even without a clinical overt disease phenotype at baseline evaluation. Moreover, PDrV in arrhythmic genes significantly influence SCD/MVA risk, regardless of phenotypic diagnosis of DCM.
Study context
- Population
- General population participants of the United Kingdom Biobank
- Participants
- 469,671 participants
- Exposure
- Predicted deleterious variants (PDrV) carriers vs noncarriers
- PDrV carriersn = 12,973
- Outcome
- Two primary outcomes: SCD/MVA and HF/HT
- Follow-up
- Median 14 years (IQR: 2)
Main finding
As reported in the abstract
PDrV carriers vs noncarriersHazard ratio (95% CI)
SCD/MVA
1.28(1.11–1.48)
HF/HT; not confirmed in subgroup without other heart diseases
1.32(1.08–1.62)
- SCD/MVA events
- 5786
- HF/HT events
- 4611
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| SCD/MVA in participants free from DCM or other heart diseases at recruitment (subgroup) · SCD/MVA risk solely associated with ACM genes | 1.34 (1.07–1.69) | |
| 0.512Hazard ratio (log scale) |
Baseline characteristics
- Females
- 54.2%
- Median age at baseline (IQR)
- 53.5 (IQR: 10.3)
- PDrV found
- 12,973 (2.8%)
Penetrance for DCM in carriers
- DCM penetrance
- 1.0%
Original publication
Arrhythmic Risk in Carriers of Predicted Deleterious Rare Variants in Dilated and Arrhythmogenic Cardiomyopathy Genes. JACC Adv. Published 28 July 2026. doi:10.1016/j.jacadv.2026.103066
Summarised from the published abstract; every number is checked against it