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CMR scans may reveal lamin heart disease prognostic biomarkers, enabling clinicians to better predict which patients are most at risk, according to research.

Lamin gene (LMNA) variant carriers with preserved left ventricular systolic function have a cardiovascular magnetic resonance (CMR) phenotype of longer T₂, higher serum troponin, higher extracellular volume, and impaired strain, according to study results published online in JACC: Cardiovascular Imaging.

Biomarker Potential

In patients with lamin heart disease, male sex, nonmissense variants, first- or higher-degree atrioventricular block, nonsustained ventricular tachycardia, and echocardiographic left ventricular ejection fraction (LVEF) are known independent risk factors for a five-year risk for life-threatening ventricular tachyarrhythmia. However, traditional risk tools rely largely on clinical and electrocardiogram (ECG) data and offer limited predictive accuracy, especially in women.

“Advanced lamin heart disease is characterized by myocardial fibrosis and diastolic dysfunction, but it is currently unclear whether altered myocardial dynamics and abnormal tissue characteristics may be present earlier in the course of the disease and before left ventricular (LV) systolic dysfunction,” wrote Gabriella Captur, MD, University College London, and coauthors. “Such CMR biomarkers may have the potential to predict the development of penetrant disease, disease trajectories in overt disease, and ultimately prognosis.”

Study Design & Cohort

The researchers combined multiparametric CMR imaging with CMR-based 4-dimensional morphofunctional shape analysis “to unravel the myocardial tissue characteristics and dynamics” of patients with lamin heart disease, specifically those with LVEF 55% or greater and those with LVEF less than 55%. Additionally, they investigated the prognostic potential of CMR biomarkers in relation to major adverse cardiovascular events (MACE) in lamin heart disease.

The prospective multicenter study included 29 LMNA carriers with LVEF 55% or greater (Lamin+EF), 38 LMNA carriers with LVEF less than 50% (Lamin–EF), 73 patients with dilated cardiomyopathy with wild-type LMNA (DCMwt), and 47 healthy volunteers (HV).

Follow‑up for MACE (cardiovascular death, life‑threatening VTA, heart transplantation, or pacemaker‑requiring AV block) was four years.

Key Imaging & Biomarker Findings

In comparison to the HV group, the Lamin+EF group had longer phantom-normalized T₂ by 10, 3% higher extracellular volume, and worse myocardial dynamics, according to the study findings. However, compared with the DCMwt group, the Lamin+EF group exhibited better myocardial dynamics, higher phantom-normalized T₂ (20 vs 12), higher serum troponin (27 ng/L versus vs 5 ng/L), and higher C-reactive protein (8 mg/L vs 3 mg/L).

The researchers reported that myocardial dynamics were similar in the Lamin–EF group, but the Lamin–EF group had higher serum troponin (13 ng/L versus 5 ng/L), higher N-terminal pro–B-type natriuretic peptide (668 pg/mL versus 228 pg/mL), longer phantom-normalized T₂ by 16, and 5% higher extracellular volume than the DCMwt group.

Follow‑up analysis showed that, over four years, MACE occurred in 21% of patients with lamin versus 6% of patients with DCMwt. For patients with lamin, each 1% increase in global LGE raised the hazard for MACE by 15%, and each 1 % decrease in Procrustes trajectory size (reflecting blunted myocardial dynamics) increased risk modestly.

“We also found that patients with truncating LMNA variants displayed worse myocardial dynamics than missense and splice-site variants, which may explain their higher risk of developing MACE,” the authors noted.

Added Clinical Utility

“Our study is the first in humans to provide robust evidence that myocardial injury and edema are central features of lamin heart disease, corroborating myocardial T2 mapping and circulating serum biomarkers, in contrast to DCMwt,” the researchers wrote, concluding, “CMR-derived focal fibrosis and strain biomarkers are prognostic, and future studies should explore their added clinical utility beyond the currently available risk prediction tools.”