Heart failure & cardiomyopathiesCohort study
Disease Penetrance in Genotype-Positive But Clinically Unaffected Relatives From Families With Dilated Cardiomyopathy
- Retrospective cohort study
- consecutive relatives
- retrospectively recruited
Authors' conclusion
Rates of disease penetrance are high in genotype-positive relatives and particularly high in men and LMNA variant carriers. Baseline LVEF is strongly associated with disease penetrance.
Study context
- Population
- Genotype-positive, clinically unaffected relatives from families with dilated cardiomyopathy (DCM) and a likely pathogenic or pathogenic variant in DCM-related genes74 families
- Participants
- 130 participants
- Outcome
- Composite of:
- HF
- Malignant ventricular arrhythmia
Main finding
As reported in the abstract
Four relatives had the primary composite endpoint
3.1%
Observational data: associations, not effects.
Further findings
Phenotype development by sex · log-rank
P = 0.007
Incidence rate of phenotype development · 80 months of follow-up
- Incidence rate of phenotype development (Q1-Q3: 9.0-14.3 per 100 person-years)
- 11.6 per 100 person-years
Disease penetrance by genotype
- LMNA variant carriers had the highest incidence rate of disease penetrance (Q1-Q3: 9.8-25.7 per 100 person-years)
- 17.7 per 100 person-years
Baseline LVEF and disease penetrance
- Baseline LVEF strongly associated with disease penetrance
Appropriate ICD shock
- 3 relatives with an implantable cardiac defibrillator received an appropriate shock
- 9.4%
Original publication
Disease Penetrance in Genotype-Positive But Clinically Unaffected Relatives From Families With Dilated Cardiomyopathy. JACC Heart Fail. Published 22 August 2025. doi:10.1016/j.jchf.2025.102588
Summarised from the published abstract; every number is checked against it