Arrhythmias & electrophysiologyMeta-analysis
Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation
- Genetic association study (pooled analysis of randomised trials)
- 5 multinational TIMI trials
- exome sequencing
- replication cohort (EAST-AFNET-4)
- centrally adjudicated outcomes
Authors' conclusion
In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF hospitalizations and cardiovascular death, but not stroke.
Study context
- Population
- Patients with a history of atrial fibrillation (AF) in ENGAGE AF, FOURIER, SAVOR, PEGASUS and DECLARE421 (2.4%) carriers
- Participants
- 17,190 patients
- Comparison
- CMP-PLP carriers vs non-carriers
- CMP-PLP carriersn = 421
- Outcome
- Centrally adjudicated clinical outcomes:
- HF
- CV death
- Ischemic stroke
Pooled result
As reported in the abstract
CMP-PLP carriers vs Non-carriersHazard ratio (95% CI)P value
incident HF hospitalizations; most notably hypertrophic cardiomyopathy and arrhythmogenic RV cardiomyopathy variants
1.75(1.34–2.29)
P < 0.0001CV death (nominal); driven mainly by dilated cardiomyopathy-associated variants
1.46(1.06–2.02)
P = 0.02- history of HF; most notably dilated cardiomyopathy-associated variants
- OR 1.66; P < 0.0001
- CMP-PLP variants not associated with prevalent ischemic stroke
- OR: 0.99; P = 0.96
- CMP-PLP variants not associated with incident ischemic stroke (anticoagulation use high)
- HR: 0.95; P = 0.84
Further pooled results
Replication in EAST-AFNET-4 (n = 1,479)
- CMP-PLP variants also associated with prevalent HF and incident HF hospitalizations
Original publication
Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation. J Am Coll Cardiol. Published 9 September 2025. doi:10.1016/j.jacc.2025.06.052
Summarised from the published abstract; every number is checked against it