The Cardiovascular Magnetic Resonance Phenotype of Lamin Heart Disease
- PMID: 40372342
- DOI: 10.1016/j.jcmg.2025.01.004
The Cardiovascular Magnetic Resonance Phenotype of Lamin Heart Disease
Abstract
Background: Lamin (LMNA) heart disease is a lethal form of dilated cardiomyopathy (DCM).
Objectives: The authors explored its cardiovascular magnetic resonance (CMR) phenotype to discover prognostically useful and subclinical biomarkers.
Methods: This prospective multicenter study recruited 4 groups: LMNA carriers with left ventricular ejection fraction ≥55% (Lamin+EF), LMNA carriers with left ventricular ejection fraction <50% (Lamin-EF), individuals with DCM with wild-type LMNA (DCMwt), and healthy volunteers. Phantom-calibrated CMR comprising cines, late gadolinium enhancement, and multiparametric mapping was undertaken. Left ventricular shapes were reconstructed using generalized Procrustes analysis. Serum biomarkers were collected at the time of CMR. Using a major adverse cardiovascular events (MACE) outcome of cardiovascular death, life-threatening ventricular tachyarrhythmia, heart transplantation, or atrioventricular block requiring pacing, we explored the prognostic value of CMR metrics using Cox regression.
Results: A total of 187 individuals were recruited (50% male): 29 with Lamin+EF (38 ± 14 years), 38 with Lamin-EF (45 ± 17 years), 73 with DCMwt (45 ± 15 years), and 47 healthy volunteers (44 ± 20 years). Compared to HVs, Lamin+EF had longer phantom-normalized T2 by 10 (95% CI: 2-20), higher ECV by 3% (95% CI: 1%-6%), and worse myocardial dynamics. Compared with DCMwt participants, Lamin+EF participants had better myocardial dynamics, higher phantom-normalized T2 (20 vs 12; P = 0.010), higher serum troponin (27 ng/L vs 5 ng/L; P < 0.001), and higher C-reactive protein (8 mg/L vs 3 mg/L; P = 0.021). Lamin-EF participants had similar myocardial dynamics but higher serum troponin (13 ng/L vs 5 ng/L; P < 0.001), higher N-terminal pro-B-type natriuretic peptide (668 pg/mL vs 228 pg/mL; P = 0.025), longer phantom-normalized T2 by 16 (95% CI: 1-31), and higher extracellular volume by 5% (95% CI: 1%-9%) than DCMwt participants. Over 4 years, 21% of lamin and 6% of DCMwt participants experienced MACE (P < 0.001). In lamin participants, each 1% increase in global late gadolinium enhancement and each 1% decrease in Procrustes trajectory sizes associated with HRs for MACE of 1.15 (95% CI: 1.02-1.30) and 1.01 (95% CI: 1.01-1.02), respectively (both P ≤ 0.025).
Conclusions: The CMR phenotype of LMNA carriers with preserved left ventricular systolic function consists of longer T2, higher serum troponin levels, higher extracellular volume, and impaired strain. CMR-derived focal fibrosis and strain biomarkers are prognostic, and future studies should explore their added clinical utility beyond the currently available MACE risk prediction tools. (The Deep Phenotype of Lamin A/C Cardiomyopathy; NCT03860454).
Keywords: generalized Procustes analysis; lamin heart disease; lamin variant carrier.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Funding Support and Author Disclosures This work was funded by grants to Dr Captur from the National Institute for Health and Care Research (NIHR) Rare Diseases Translational Research Collaboration, Barts Charity HeartOME1000 Grant (MGU0427/G-001411), and the 2017 Society for Cardiovascular Magnetic Resonance Seed Grant Award. Dr Captur was also supported by the British Heart Foundation (MyoFit46 Special Programme Grant SP/20/2/34841), the British Heart Foundation Accelerator Award (AA/18/6/34223), the NIHR Invention for Innovation FAST grant scheme (iFAST NIHR205960), and the NIHR University College London Hospitals Biomedical Research Centre (BRC). Dr Moon was directly and indirectly supported by the UCL Hospitals NIHR BRC at Barts Hospital. Dr Al-Farih was supported by the Saudi Arabian Cultural Bureau in London. Dr Hughes was supported by the British Heart Foundation, the Economic and Social Research Council, the Horizon 2020 Framework Programme of the European Union, the National Institute on Aging, the NIHR University College London Hospitals BRC, and the UK Medical Research Council, and works in a unit that receives support from the UK Medical Research Council. This work was also supported by the NIHR Barts BRC (NIHR203330), a delivery partnership of the Barts Health NHS Trust, Queen Mary University of London, St George’s University Hospitals NHS Foundation Trust, and St George’s, University of London. None of the funders were involved in the study design, data collection, analysis, or interpretation, or in the decision to submit for publication. Dr Moon is the chief executive officer of MyCardium AI; and has served on the advisory board for Genzyme and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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