Heart failure & cardiomyopathiesSecondary analysis
Clinical Characteristics of Heart Failure with Reduced Ejection Fraction Patients with Rare Pathogenic Variants in Dilated Cardiomyopathy-Associated Genes: A Subgroup Analysis of the PARADIGM-HF Trial
- Secondary analysis of the PARADIGM-HF randomised trial
- post hoc analysis
Authors' conclusion
Deleterious pLoF variants in genes with definitive/strong association with DCM were identified in ∼5% of HFrEF patients from a PARADIGM-HF trial subset, who were younger, had lower ejection fraction and were less likely to have had an ischaemic aetiology.
Study context
- Population
- Heart failure and reduced ejection fraction (HFrEF) participants of the Phase 3 PARADIGM-HF trial with whole-exome sequence datawhole-exome sequence data
- Participants
- 1,412 participants
- Comparison
- Predicted loss-of-function (pLoF) variant carriers vs non-carriers in dilated cardiomyopathy (DCM)-associated genes
- Tier-1 carriersn = 68
- Primary endpoint
- Prevalence of pLoF variants in DCM-associated genes, by gene tier
Primary result
As reported in the abstract
≥1 pLoF variant in 8 tier-1 genes (68 of 1412); Titin most commonly affected
4.8%
≥1 pLoF variant in all 44 genes
7.5%
Further findings
Baseline characteristics, tier-1 carriers vs non-carriers · younger · adjusted P values
difference 4 · padj = 4 × 10-3
BMI Tier-1 carriers 27.8 kg/m² · Non-carriers 29.4 kg/m² · padj = 3.2 × 10-3
EF
padj = 5.8 × 10-3
Ischaemic aetiology
padj = 4 × 10-4
Prevalence in idiopathic aetiology (subgroup)
- Tier-1 variants only (23/229)
- 10.0%
- Tier-1, −2 or −3 variants (29/229)
- 12.6%
Original publication
Summarised from the published abstract; every number is checked against it