Naidoo Nerissa, Bajwa Gurjyot, Duvuru Ruthwik, Banerjee Yajnavalka
Department of Basic Medical Sciences, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates.
JMIR Res Protoc. 2020 Mar 5;9(3):e17241. doi: 10.2196/17241.
Cardiovascular disease (CVD) remains the leading cause of death in the United Arab Emirates (UAE). One of the common CVDs is hypertrophic cardiomyopathy (HCM). Recent studies conducted in heart cells of mice have shown that this condition involves a chemical modification called hydroxymethylation of the DNA of heart cells.
Objectives of the proposed research are to profile the distribution of 5-hydroxymethylation in the cardiomyocyte (CMC) genome of cadaveric cardiac tissue and cardiac biopsy specimens; to compare the hydroxymethylome of cadaveric CMCs with that of cardiac biopsy specimens from HCM patients and/or cardiac transplant patients (control) undergoing cardiac catheterization; to histologically appraise sarcomere distribution and mitochondrial morphology of CMCs in the presence of HCM; to correlate the mitochondrial genome with the HCM phenotype; and to integrate anatomy with biochemistry and genetics into the instructional design of HCM in the core medical curriculum at Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU).
Normal and hypertrophic heart specimens will be obtained from 8 whole-body cadavers (2/8, 25% control and 6/8, 75% HCM). Myocardial biopsy specimens will be obtained from cardiothoracic and transplant units at the Cleveland Clinic in Abu Dhabi, UAE. As this is a proof-of-concept study, we plan to recruit 5 patients with HCM, where HCM has been diagnosed according to the guidelines of the 2014 European Society of Cardiology Guidelines. Patients with valvular heart disease, history of myocarditis, regular alcohol consumption, or cardiotoxic chemotherapy will be excluded. The control biopsy specimens will be obtained from patients who had received heart transplants. Three investigational approaches will then be employed: (1) gross anatomical evaluation, (2) histological analysis, and (3) profiling and analysis of the hydroxymethylome. These investigations will be pursued with minor modifications, if required, to the standard protocols and in accordance with institutional policy. The objective associated with the education of health professionals will be addressed through a strategy based on Graham's knowledge translation model.
This study is at the protocol-development stage. The validated questionnaires have been identified in relation to the objectives. The MBRU and the Cleveland Clinic Abu Dhabi Institutional Review Board (IRB) are reviewing this study. Further clarification and information can be obtained from the MBRU IRB. There is funding in place for this study (MBRU-CM-RG2019-08). Currently, we are in the process of standardizing the protocols with respect to the various molecular techniques to be employed during the course of the study. The total duration of the proposed research is 24 months, with a provision for 6 months of a no-cost extension.
The spectrum of CVDs has recently received significant focus from the public health sector in the UAE. HCM is a common familial heart disease, contributing to the sudden increase in the mortality rate of young Emiratis in the UAE. Incorporating artificial intelligence into the identification of epigenetic risk factors associated with HCM will promote accurate diagnosis and lead to the development of improved management plans, hence, positive patient outcomes. Furthermore, integration of these findings into the instructional design of undergraduate, postgraduate, and continuous professional development medical curricula will further contribute to the body of knowledge regarding HCM.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/17241.
心血管疾病（CVD）仍是阿拉伯联合酋长国（UAE）的主要死因。常见的心血管疾病之一是肥厚型心肌病（HCM）。最近在小鼠心脏细胞中进行的研究表明，这种病症涉及一种称为心脏细胞DNA羟甲基化的化学修饰。
拟开展研究的目的包括描绘尸体心脏组织和心脏活检标本的心肌细胞（CMC）基因组中5-羟甲基化的分布；比较尸体CMC的羟甲基化组与接受心导管检查的HCM患者和/或心脏移植患者（对照）的心脏活检标本的羟甲基化组；在存在HCM的情况下，对CMC的肌节分布和线粒体形态进行组织学评估；将线粒体基因组与HCM表型相关联；并将解剖学与生物化学和遗传学整合到穆罕默德·本·拉希德医学与健康科学大学（MBRU）核心医学课程中HCM的教学设计中。
将从8具全身尸体获取正常和肥厚心脏标本（2/8，25%为对照，6/8，75%为HCM）。心肌活检标本将从阿联酋阿布扎比克利夫兰诊所的心胸外科和移植科室获取。由于这是一项概念验证研究，我们计划招募5例HCM患者，其中HCM已根据2014年欧洲心脏病学会指南的标准进行诊断。患有瓣膜性心脏病、心肌炎病史、经常饮酒或接受心脏毒性化疗的患者将被排除。对照活检标本将从接受心脏移植的患者中获取。然后将采用三种研究方法：（1）大体解剖评估，（2）组织学分析，以及（3）羟甲基化组的描绘和分析。如有需要，将对标准方案进行微小修改，并按照机构政策进行这些研究。与卫生专业人员教育相关的目标将通过基于格雷厄姆知识转化模型的策略来实现。
本研究处于方案制定阶段。已经确定了与目标相关的经过验证的问卷。MBRU和阿布扎比克利夫兰诊所机构审查委员会（IRB）正在审查本研究。可从MBRU IRB获得进一步的澄清和信息。本研究有资金支持（MBRU-CM-RG2019-）。目前，我们正在对研究过程中要采用的各种分子技术的方案进行标准化。拟开展研究的总时长为24个月，另有6个月的无成本延期规定。
心血管疾病谱最近受到阿联酋公共卫生部门的高度关注。HCM是一种常见的家族性心脏病，导致阿联酋年轻阿联酋人死亡率突然上升。将人工智能纳入与HCM相关的表观遗传风险因素的识别将促进准确诊断，并有助于制定改进的管理计划，从而为患者带来积极的治疗结果。此外，将这些研究结果整合到本科、研究生和持续专业发展医学课程的教学设计中，将进一步丰富有关HCM的知识体系。
国际注册报告识别码（IRRID）：PRR1-10.2196/17241。
