Arrhythmias & electrophysiology
Predicted Risk of Ventricular Arrhythmias in a Genome-First Population With Genetic Risk for Arrhythmogenic Right Ventricular Cardiomyopathy
Authors' conclusion
The predicted 5-year risk of VA in individuals ascertained via population genomic screening for desmosome variants is low (3.9%; 1.6% for fast VA) but may vary by affected gene and ARVC task force criteria burden.
Study context
- Population
- Individuals harboring a pathogenic/likely pathogenic variant in a desmosome gene (PKP2, DSP, DSG2, or DSC2) with cardiac imaging in follow-up and no prior sustained ventricular arrhythmiaof 254 individuals with a clinically confirmed pathogenic/likely pathogenic desmosome variant
- Participants
- 113 individuals
- Exposure
- ARVC risk calculator predicted risk compared with outcomes in the first 5 years after genetic result return
- possible diagnosisn = 82
- borderline diagnosisn = 22
- definite diagnosisn = 9
Methodological detailsGeisinger MyCode Genomic Screening and Counseling program
- Geisinger MyCode Genomic Screening and Counseling program
Main finding
As reported in the abstract
Predicted 5-year VA risk · 5 years
Median 5-year predicted ventricular arrhythmia (VA) risk
3.9%
2.3%–6.6%
Calculator derivation cohort
20.6%
Observational data: associations, not effects.
Further findings
| Outcome | Values |
|---|---|
| Predicted VA risk by nongenetic ARVC task force criteria | any nongenetic ARVC task force criteria 6.3% (range as printed 2.5–13.2%) · without 3.7% (range as printed 2.2–5.6%) |
| Predicted VA risk by gene | DSP 6.1% (range as printed 3.9–7.8%) · PKP2 3.4% (range as printed 2.2–5.3%) |
- Predicted VA risk by nongenetic ARVC task force criteria: P =0.01
- Predicted VA risk by gene: P =0.01
Predicted risk of fast VA
- Risk of fast VA
- 1.6% (1.0%-2.9%)
Observed sustained VA events · median 3.0 years of follow-up (≤5 years only)
- No sustained VA events were observed
Cohort characteristics
- Median age
- 56 [interquartile range, 42-66]
- Female
- 71%
Original publication
Predicted Risk of Ventricular Arrhythmias in a Genome-First Population With Genetic Risk for Arrhythmogenic Right Ventricular Cardiomyopathy. Circ Arrhythm Electrophysiol. Published 24 February 2025. doi:10.
Summarised from the published abstract; every number is checked against it