Arrhythmias & electrophysiologyCohort study
Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy
- Retrospective cohort study
- multicentre
- international registry and tertiary cardiomyopathy centres
Authors' conclusion
In this retrospective cohort study, truncating LMNA variants were associated with worse arrhythmic outcomes independent of variant position, whereas missense variants affecting the tail domain and located in exons 7 through 12 had better arrhythmic and heart failure outcomes.
Study context
- Population
- Patients with likely pathogenic/pathogenic LMNA variants and no prior malignant ventricular arrhythmia
- Participants
- 718 patients
- Exposure
- Truncating vs missense LMNA variants, and by variant location
- Outcome
- Time to VA (SCD, appropriate ICD therapy or other hemodynamically unstable VA)
- Follow-up
- Median 4.2 years
Main finding
Malignant VA
Hazard ratio
1.72
95% CI 1.19–2.48
P = 0.004
Truncating vs Missense
HR 1.72 (95% CI 1.19–2.48); P = 0.004
As reported in the abstract
- Patients with malignant ventricular arrhythmia (VA)
- 223
Observational data: associations, not effects.
Secondary outcomes
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| Advanced HF (nonsudden cardiac death, LV assist device or cardiac transplant) | 0.94 (0.64–1.40) | P = 0.77 | |
| Malignant VA, missense variants by location (subgroup) — Missense, tail domain vs Missense · multivariable analysis | 0.35 (0.16–0.78) | P = 0.02 | |
| Malignant VA, missense variants by location (subgroup) — Missense, exons 7 through 12 vs Missense · multivariable analysis | 0.39 (0.17–0.89) | P = 0.035 | |
| 0.10.31310Hazard ratio (log scale) |
- Advanced HF (nonsudden cardiac death, LV assist device or cardiac transplant) — Patients with advanced HF
- 109
Primary and secondary outcomes, truncating variants by gene location or transcript position (subgroup)
- No significant differences
Original publication
Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy. JAMA Cardiol. Published 1 September 2025. doi:10.1001/jamacardio.2025.2069
Summarised from the published abstract; every number is checked against it