Characterization and Natural History of Patients with LMNA -Related Dilated Cardiomyopathy in the Phase 3 REALM-DCM Trial
- Trial terminated due to futility without safety concern
Authors' conclusion
Findings confirm the significant morbidity and mortality associated with LMNA-related DCM despite the standard of care management. Typical measures of HF, including 6MWT distance, KCCQ-OS score and NT-proBNP concentration, were variable but correlated with NYHA class.
Study context
- Population
- Patients with stable LMNA-related dilated cardiomyopathy (DCM), ICD or CRT-D, and New York Heart Association (NYHA) Class II/III heart failure (HF) symptoms
- Participants
- 77 patients
- Comparison
- NYHA Class II vs NYHA Class III
Methodological detailsphase 3, pooled data, descriptive, Enrolment 2018–2022
- Phase 3
- Pooled data
- Descriptive
- Enrolment 2018–2022
Primary result
As reported in the abstract
Baseline phenotype · baseline
LVEF
| Outcome | NYHA Class II | NYHA Class III |
|---|---|---|
| 6MWT distance | 413 m | 326 m |
| KCCQ-OS score | 70 | 43 |
| NT-proBNP | 799 pg/mL | 1216 pg/mL |
- Median age, years (range 23-72)
- 53
- Male
- 57%
- Pathogenic or likely pathogenic LMNA variant
- 88%
- Variant of uncertain significance with concordant phenotype
- 12%
- Missense variant (confirmed sequencing)
- 55%
- AF
- 60%
- NYHA Class II at baseline
- 79%
- NYHA Class III at baseline
- 21%
- Median left ventricular ejection fraction (LVEF) (range 23-62)
- 42%
- Median 6MWT distance (range 173-481)
- 403 m
- Median Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score (range 18-97)
- 67
- Median NT-proBNP (range 57-5248)
- 866 pg/mL
Further findings
| Outcome | NYHA Class II | NYHA Class III |
|---|---|---|
| Clinical events during follow-up · median follow-up 73 weeks (range: 0.4-218) | ||
| Worsening HF or all-cause death | 6 | 4 |
| All-cause mortality | 3 | 3 |
- Clinical events during follow-up — VT
- 25%
- Clinical events during follow-up — VF
- 8%
- Clinical events during follow-up — Composite of worsening HF (adjudicated HF hospitalization or urgent care visit) or all-cause death
- 10 (13%)
- Clinical events during follow-up — All-cause mortality
- 6 (8%)
Change from baseline in 6MWT, KCCQ-OS and NT-proBNP · during follow-up
- Variable change from baseline in 6MWT, KCCQ-OS and NT-proBNP
Original publication
Characterization and Natural History of Patients with LMNA -Related Dilated Cardiomyopathy in the Phase 3 REALM-DCM Trial. ESC Heart Fail. Published 15 August 2024. doi:10.
Summarised from the published abstract; every number is checked against it