ArticlemedRxiv : the preprint server for health sciences2024
Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers.
Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) exhibit structural and functional cardiac abnormalities. We aimed to identify imaging biomarkers for pre-clinical cardiomyopathy in healthy individuals carrying cardiomyopathy-associated variants (G+). Methods: We included 40,169 UK biobank participants without cardiac disease who had cardiac magnetic resonance imaging (CMR) measurements and whole exome sequencing. We first validated 22 CMR measurements by associating them with incident atrial fibrillation (AF) or heart failure (HF). We subsequently assessed associations of these measurements with HCM or DCM G+, or specific genes, utilising generalised linear models conditional on cardiac risk factors. Results: Thirteen CMR measurements were associated with incident AF and fifteen with HF. These included left-ventricular (LV) ejection fraction (EF) (hazard ratio [HR] 0.61, 95% confidence interval [95%CI] 0.54; 0.69) for HF and indexed maximum left atrial volume (LA-Vi max; HR1.47, 95%CI 1.29; 1.67) for AF. Five measurements associated with HCM G+, amongst which right ventricular (RV) end-systolic volume (RV-ESV; OR 0.62, 95%CI 0.53; 0.74), RV-EF (OR 1.36, 95%CI 1.19; 1.55), and right atrial EF (OR 1.22, 95%CI 1.08; 1.39). All associations overlapping with incident disease and HCM had opposite effect directions, such as RV-ESV with HF (OR 1.22, 95%CI 1.07; 1.40). Two CMR measurements associated with DCM G+: LV-ESVi (OR 1.35, 95%CI 1.15; 1.58) and LV-EF (OR 0.75, 95%CI 0.64; 0.88). Due to heterogeneity, we explored associations with individual cardiomyopathy genes, finding MAPSE associated with Conclusion: We identified right heart CMR measurements associated with HCM G+ in healthy individuals, indicating early compensation of cardiac function. LV measurements were associated with DCM G+, where the CMR associations varied across individual DCM genes, suggesting distinct early pathophysiology.
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