The cardiovascular magnetic resonance phenotype of Lamin heart disease
Topriceanu, Constantin-Cristian Al-Farih, Mashael Joy, George Chan, Fiona Webber, Matt Ilie-Ablachim, Denis C Shiwani, Hunain Tamang, Mansoon Banks, Catherine Pettit, Stephen
Topriceanu, Constantin-Cristian
Al-Farih, Mashael
Joy, George
Chan, Fiona
Webber, Matt
Ilie-Ablachim, Denis C
Shiwani, Hunain
Tamang, Mansoon
Banks, Catherine
Pettit, Stephen
Affiliation
University College London; Barts Health NHS Trust; University Politechnica of Bucharest; Royal Papworth Hospital NHS Foundation Trust; Queen Mary University London; Alan Turing Institute; Deutsches Herzzentrum der Charité; Charité-Universitätsmedizin Berlin; Cleveland Clinic; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; Sapienza University of Rome; National Institute of Health Bethesda; Fondazione Toscana Gabriele Monasterio; Royal Free London NHS Foundation Trust
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Publication date
2025-05-14
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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).
Citation
Topriceanu CC, Al-Farih M, Joy G, Chan F, Webber M, Ilie-Ablachim DC, Shiwani H, Tamang M, Banks C, Pettit S, Petersen SE, O'Brien B, Hughes AD, Pierce I, Moody WE, Steeds RP, Puddu PE, Kellman P, Savvatis K, Mohiddin S, Moon JC, Barison A, Piras P, Captur G. The Cardiovascular Magnetic Resonance Phenotype of Lamin Heart Disease. JACC Cardiovasc Imaging. 2025 Jun;18(6):644-660. doi: 10.1016/j.jcmg.2025.01.004. Epub 2025 May 14.
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Article