Cardiac magnetic resonance markers of pre-clinical hypertrophic and dilated cardiomyopathy in genetic variant carriers.

IF 7 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

BMC Medicine Pub Date : 2025-07-15 DOI:10.1186/s12916-025-04226-4

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

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引用次数: 0

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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基因变异携带者临床前肥厚和扩张型心肌病的心脏磁共振标志物。

背景：肥厚型心肌病（HCM）和扩张型心肌病（DCM）患者表现为心脏结构和功能异常。我们的目的是在携带心肌病相关变异（G +）的健康参与者中确定临床前心肌病的成像生物标志物。方法：我们在心脏磁共振成像（CMR）和全外显子组测序时纳入了40,169名无心脏病的英国生物银行参与者。我们通过将22项CMR测量与房颤（AF）或心力衰竭（HF）事件联系起来，验证了它们的有效性。随后，我们利用以心脏危险因素为条件的广义线性模型，评估了这些CMR测量与HCM G+、DCM G+或特定基因的关联。结果：13例CMR测量与AF事件相关，15例与HF事件相关。包括左心室射血分数（EF）；风险比[HR] 0.61, 95%可信区间[95% ci] 0.54；0.69)，指标最大左房容积(LAVi max；Hr 1.47, 95%ci 1.29；5项测量与HCM G +相关，其中右心室（RV）收缩末期容积(RV- esv；优势比[OR] 0.62, 95%CI 0.53；0.74), rv-ef (or 1.36, 95%ci 1.19；1.55)，右心房（RA） EF (OR 1.22, 95%CI 1.08；1.39)。与突发疾病和HCM G +重叠的关联具有相反的影响方向，如RV-ESV与HF (HR 1.22, 95%CI 1.07；1.40)。两项CMR测量与DCM G +相关：LV-ESVi (OR 1.35, 95%CI 1.15；1.58)和LV-EF (OR 0.75, 95%CI 0.64；0.88)。我们观察到与个体心肌病基因的显著关联，发现二尖瓣环平面收缩偏移与TTN和TNNT2相关，LA泵容积和RA-EF与MYH7相关。结论：我们确定了健康人右心CMR测量与HCM G +相关，表明早期心功能代偿。LV测量与DCM G +相关，其中CMR关联因个体DCM基因而异，提示不同的早期病理生理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Medicine 医学-医学：内科

CiteScore

13.10

自引率

1.10%

发文量

435

审稿时长

4-8 weeks

期刊介绍： BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.