Arrhythmias & electrophysiology
Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation: Results in 18,000 Clinical Trial Participants
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
Methodological detailspooled analysis of randomised trials, 5 multinational TIMI trials, exome sequencing, replication cohort (EAST-AFNET-4), centrally adjudicated outcomes
- Pooled analysis of randomised trials
- 5 multinational TIMI trials
- Exome sequencing
- Replication cohort (EAST-AFNET-4)
- Centrally adjudicated outcomes
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: Results in 18,000 Clinical Trial Participants. J Am Coll Cardiol. Published 9 September 2025. doi:10.
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