Heart failure & cardiomyopathiesCohort study
Genotype-Specific Outcomes of Desmosomal Cardiomyopathies
- Cohort study
- consecutive patients
- multivariable analysis
Authors' conclusion
Among carriers of DGVs, genotype was associated with arrhythmic and HF outcomes, with type and location of the variant further modulating the natural history.
Study context
- Population
- Carriers of pathogenic and rare VUS desmosomal gene variants (DGVs) referred for desmosomal gene screening214 families
- Participants
- 533 carriers
- Exposure
- Desmosomal genotypes vs nonmissense PKP2 variants
- Double DGVsn = 30
- Outcome
- Life-threatening arrhythmic event (SCD, aborted cardiac arrest or hemodynamically unstable VT); end-stage HF (fatal HF episode or cardiac transplantation)
Main finding
As reported in the abstract
Life-threatening arrhythmic event
Each group vs nonmissense PKP2Hazard ratio (95% CI)P value
Nonmissense DSP
2.3(1.3–4.1)
P = 0.008Hotspot missense DSP
2.7(1.2–6.2)
P = 0.010Hotspot missense PKP2
3.6(2.0–6.5)
P < 0.001Double DGVs
3.4(1.7–6.9)
P < 0.001Male sex
1.7(1.1–2.8)
P = 0.021- Overall life-threatening arrhythmic event
- 83 of 533 (16%)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| End-stage HF — Nonmissense DSP vs Nonmissense PKP2 | 5.0 (1.5–18.2) | P = 0.009 | |
| End-stage HF — Double DGVs vs Nonmissense PKP2 | 4.7 (1.0–19.3) | P = 0.044 | |
| 0.050.21520Hazard ratio (log scale) |
- End-stage heart failure (HF) — Overall end-stage HF
- 14 of 533 (3%)
Original publication
Genotype-Specific Outcomes of Desmosomal Cardiomyopathies. Circulation. Published 23 May 2025. doi:10.1161/circulationaha.124.073475
Summarised from the published abstract; every number is checked against it