Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers
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 participants carrying cardiomyopathy-associated variants (G...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12916-025-04226-4 |
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| author | Philip M. Croon Marion van Vugt Cornelis P. Allaart Bram Ruijsink Perry M. Elliott Folkert W. Asselbergs Rohan Khera Connie R. Bezzina Michiel Winter A. Floriaan Schmidt |
| author_facet | Philip M. Croon Marion van Vugt Cornelis P. Allaart Bram Ruijsink Perry M. Elliott Folkert W. Asselbergs Rohan Khera Connie R. Bezzina Michiel Winter A. Floriaan Schmidt |
| author_sort | Philip M. Croon |
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| description | 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 participants carrying cardiomyopathy-associated variants (G +). Methods We included 40,169 UK Biobank participants free of cardiac disease at the time of cardiac magnetic resonance imaging (CMR) and with whole exome sequencing. We validated 22 CMR measurements by associating them with incident atrial fibrillation (AF) or heart failure (HF). We subsequently assessed associations of these CMR measurements with HCM G+, DCM G + , or specific genes, utilising generalised linear models conditional on cardiac risk factors. Results Thirteen CMR measurements were associated with incident AF and 15 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 (LAVi max; HR 1.47, 95%CI 1.29; 1.67) for AF. Five measurements associated with HCM G + , amongst which right ventricular (RV) end-systolic volume (RV-ESV; odds ratio [OR] 0.62, 95%CI 0.53; 0.74), RV-EF (OR 1.36, 95%CI 1.19; 1.55), and right atrial (RA) EF (OR 1.22, 95%CI 1.08; 1.39). Associations overlapping with incident disease and HCM G + had opposite effect directions, such as RV-ESV with HF (HR 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). We observed significant associations with individual cardiomyopathy genes, finding that mitral annular plane systolic excursion associated with TTN and TNNT2, and LA pump volume and RA-EF associated with MYH7. Conclusions We identified right-heart CMR measurements associated with HCM G + in healthy individuals, indicating early compensation of cardiac function. LV measurements associated with DCM G + , where CMR associations varied across individual DCM genes, suggesting distinct early pathophysiology. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-2b59e21e51a8413f82b2d1ce37aa39b72025-08-20T03:46:07ZengBMCBMC Medicine1741-70152025-07-0123111310.1186/s12916-025-04226-4Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriersPhilip M. Croon0Marion van Vugt1Cornelis P. Allaart2Bram Ruijsink3Perry M. Elliott4Folkert W. Asselbergs5Rohan Khera6Connie R. Bezzina7Michiel Winter8A. Floriaan Schmidt9Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centre, University of AmsterdamDepartment of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centre, University of AmsterdamDepartment of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centre, University of AmsterdamDivision Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht UniversityBarts Heart Centre, St. Bartholomew’s HospitalDepartment of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centre, University of AmsterdamSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of MedicineAmsterdam Cardiovascular Sciences, Heart Failure and ArrhythmiasDepartment of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centre, University of AmsterdamDepartment of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centre, University of AmsterdamAbstract 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 participants carrying cardiomyopathy-associated variants (G +). Methods We included 40,169 UK Biobank participants free of cardiac disease at the time of cardiac magnetic resonance imaging (CMR) and with whole exome sequencing. We validated 22 CMR measurements by associating them with incident atrial fibrillation (AF) or heart failure (HF). We subsequently assessed associations of these CMR measurements with HCM G+, DCM G + , or specific genes, utilising generalised linear models conditional on cardiac risk factors. Results Thirteen CMR measurements were associated with incident AF and 15 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 (LAVi max; HR 1.47, 95%CI 1.29; 1.67) for AF. Five measurements associated with HCM G + , amongst which right ventricular (RV) end-systolic volume (RV-ESV; odds ratio [OR] 0.62, 95%CI 0.53; 0.74), RV-EF (OR 1.36, 95%CI 1.19; 1.55), and right atrial (RA) EF (OR 1.22, 95%CI 1.08; 1.39). Associations overlapping with incident disease and HCM G + had opposite effect directions, such as RV-ESV with HF (HR 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). We observed significant associations with individual cardiomyopathy genes, finding that mitral annular plane systolic excursion associated with TTN and TNNT2, and LA pump volume and RA-EF associated with MYH7. Conclusions We identified right-heart CMR measurements associated with HCM G + in healthy individuals, indicating early compensation of cardiac function. LV measurements associated with DCM G + , where CMR associations varied across individual DCM genes, suggesting distinct early pathophysiology.https://doi.org/10.1186/s12916-025-04226-4Dilated cardiomyopathyCardiac magnetic resonanceHypertrophic cardiomyopathyWhole exome sequencingGenetics |
| spellingShingle | Philip M. Croon Marion van Vugt Cornelis P. Allaart Bram Ruijsink Perry M. Elliott Folkert W. Asselbergs Rohan Khera Connie R. Bezzina Michiel Winter A. Floriaan Schmidt Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers BMC Medicine Dilated cardiomyopathy Cardiac magnetic resonance Hypertrophic cardiomyopathy Whole exome sequencing Genetics |
| title | Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers |
| title_full | Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers |
| title_fullStr | Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers |
| title_full_unstemmed | Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers |
| title_short | Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers |
| title_sort | cardiac magnetic resonance markers of pre clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers |
| topic | Dilated cardiomyopathy Cardiac magnetic resonance Hypertrophic cardiomyopathy Whole exome sequencing Genetics |
| url | https://doi.org/10.1186/s12916-025-04226-4 |
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