Related Experiment Video
Updated: May 16, 2025
Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
The Cardiovascular Magnetic Resonance Phenotype of Lamin Heart Disease
Constantin-Cristian Topriceanu1, Mashael Al-Farih1, George Joy1
1MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom; Cardiac MRI Unit, Barts Heart Centre, London, United Kingdom.
Insights
Cardiovascular magnetic resonance (CMR) reveals distinct phenotypes in Lamin A/C (LMNA) heart disease, identifying longer T2, higher extracellular volume, and impaired strain as key indicators. These CMR biomarkers are prognostic for major adverse cardiovascular events (MACE) in LMNA carriers.
Area of Science:
- Cardiology
- Cardiovascular Imaging
- Genetics
Background:
- Lamin A/C (LMNA) gene mutations cause a lethal form of dilated cardiomyopathy (DCM).
- Early identification of prognostic biomarkers in LMNA carriers is crucial for timely intervention.
Purpose of the Study:
- To characterize the cardiovascular magnetic resonance (CMR) phenotype in LMNA carriers.
- To identify subclinical and prognostically significant biomarkers using CMR.
Main Methods:
- Prospective multicenter study comparing LMNA carriers (preserved and reduced ejection fraction), DCM with wild-type LMNA (DCMwt), and healthy volunteers.
- Utilized phantom-calibrated CMR (cines, late gadolinium enhancement, multiparametric mapping) and serum biomarkers.
- Assessed major adverse cardiovascular events (MACE) over 4 years using Cox regression.
Main Results:
- LMNA carriers with preserved ejection fraction showed longer T2, higher extracellular volume (ECV), and impaired myocardial dynamics compared to healthy volunteers.
- LMNA carriers exhibited higher serum troponin and C-reactive protein levels than DCMwt.
- Increased global late gadolinium enhancement and decreased Procrustes trajectory size predicted MACE in LMNA participants.
Conclusions:
- The CMR phenotype in LMNA carriers with preserved systolic function includes longer T2, higher ECV, and impaired strain.
- CMR-derived focal fibrosis and strain are prognostic biomarkers for LMNA cardiomyopathy.
- Further research is needed to integrate these CMR biomarkers into clinical risk prediction tools.
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).
