| Title: |
Characterization and natural history of patients with LMNA-related dilated cardiomyopathy in the phase 3 REALM-DCM trial |
| Authors: |
Garcia-Pavia, P; Lakdawala, NK; Sinagra, G; Ripoll-Vera, T; Afshar, K; Priori, SG; Ware, JS; Owens, A; Li, H; Angeli, FS; Elliott, P; MacRae, CA; Judge, DP |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
Imperial College London: Spiral |
| Subject Geographic: |
England |
| Description: |
AIMS: LMNA-related dilated cardiomyopathy (DCM) is a rare disease with an incompletely defined phenotype. The phase 3 REALM-DCM trial evaluated a potential disease-modifying therapy for LMNA-related DCM but was terminated due to futility without safety concern. This study utilized pooled data from REALM-DCM to descriptively characterize the phenotype and progression of LMNA-related DCM in a contemporary cohort of patients using common heart failure (HF) measures. METHODS: REALM-DCM enrolled patients with stable LMNA-related DCM, an implanted cardioverter defibrillator or cardiac resynchronization therapy defibrillator, and New York Heart Association (NYHA) Class II/III HF symptoms. RESULTS: Between 2018 and 2022, 77 patients took part in REALM-DCM. The median patient age was 53 years (range: 23-72), and 57% were male. Overall, 88% of patients had a pathogenic or likely pathogenic LMNA variant, and 12% had a variant of uncertain significance with a concordant phenotype. Among patients with confirmed sequencing, 55% had a missense variant. Atrial fibrillation was present in 60% of patients; 79% of all patients had NYHA Class II and 21% had NYHA Class III HF symptoms at baseline. Median (range) left ventricular ejection fraction (LVEF), 6 min walk test (6MWT) distance, Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration at baseline were 42% (23-62), 403 m (173-481), 67 (18-97) and 866 pg/mL (57-5248), respectively. LVEF, 6MWT distance and KCCQ-OS score were numerically lower in patients who had NYHA Class III versus II symptoms at baseline (LVEF: 38% vs. 43%; 6MWT distance: 326 vs. 413 m; and KCCQ-OS score: 43 vs. 70), whereas NT-proBNP concentration was higher (1216 vs. 799 pg/mL). Median follow-up was 73 weeks (range: 0.4-218; 73 in NYHA Class II and 75 in NYHA Class III). Patients displayed variable change from baseline in 6MWT, KCCQ-OS and NT-proBNP values during follow-up. Overall, 25% of patients experienced ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
ESC Heart Failure; http://hdl.handle.net/10044/1/114629 |
| DOI: |
10.1002/ehf2.14955 |
| Availability: |
http://hdl.handle.net/10044/1/114629; https://doi.org/10.1002/ehf2.14955 |
| Rights: |
© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.7B9D50B8 |
| Database: |
BASE |