ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).
ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).
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DOI：
10.1007/s12471-013-0478-8
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发表时间：
2013-12
影响因子：
2
通讯作者：
van der Velden, J.
中科院分区：
文献类型：
--
作者：
Guclu, A.;Germans, T.;Witjas-Paalberends, E. R.;Stienen, G. J. M.;Brouwer, W. P.;Harms, H. J.;Marcus, J. T.;Vonk, A. B. A.;Stooker, W.;Yilmaz, A.;Klein, P.;ten Berg, J. M.;Kluin, J.;Asselbergs, F. W.;Lammertsma, A. A.;Knaapen, P.;van Rossum, A. C.;van der Velden, J.
肥厚性心肌病（HCM）是一种常染色体显性心脏病，主要由编码肉瘤蛋白的基因突变引起。HCM的特征是在没有其他心脏或全身疾病的情况下，左心室（LV）不对称肥大。目前缺乏特异性治疗来预防或逆转突变携带者和HCM患者的心功能障碍和肥厚。先前的研究表明，肌瘤突变增加了心脏收缩的能量消耗，导致心肌功能障碍和肥大。通过使用翻译方法，我们的目的是确定心肌能量代谢紊乱在多大程度上是HCM疾病进展的基础。肥厚性梗阻性心肌病（HOCM）患者和主动脉瓣狭窄（AVS）患者将在肌切除术或主动脉瓣置换术+间隔活检术前和术后4个月分别进行正电子发射断层扫描（PET）和心血管磁共振成像（CMR）并进行组织标记。肌瘤切除组织或间隔活检将用于确定肌节在体外收缩的效率，并将结果与体内心脏表现进行比较。健康受试者和非肥厚型HCM突变携带者作为对照组。我们的研究将揭示在HCM的疾病进展过程中，心脏能量的扰动是否会恶化，以及这些变化是否归因于心脏重塑或肌节突变本身的存在。对HOCM和AVS患者肥大心肌的体外研究将确定肌瘤突变是否会增加人心肌肌瘤的ATP消耗。我们对HOCM和AVS患者的随访影像学研究将揭示心脏手术是否能恢复受损的心脏能量。
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.
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影响因子：
37.8
作者：
Cerqueira, MD;Weissman, NJ;Verani, MS
通讯作者：
Verani, MS
影响因子：
15.9
作者：
Javadpour, MM;Tardiff, JC;Ingwall, JS
通讯作者：
Ingwall, JS
影响因子：
5.5
作者：
Montgomery, DE;Tardiff, JC;Chandra, M
通讯作者：
Chandra, M
影响因子：
15.9
作者：
Spindler, M;Saupe, KW;Ingwall, JS
通讯作者：
Ingwall, JS
影响因子：
168.9
作者：
Marian, AJ
通讯作者：
Marian, AJ