JMIR Publications

ABSTRACT

Background:

Cardiovascular disease remains the leading cause of death in the United Arab Emirates (UAE), accounting for over two-thirds of all deaths. One of the common cardiovascular diseases is Hypertrophic Cardiomyopathy (HCM), in which the heart muscle becomes abnormally thick and is unable to pump blood adequately. Recent studies conducted in the heart’s cells of the mice have shown that this condition involves a chemical modification called “hydroxymethylation” of the DNA of the heart cells.

Objective:

In-line, objectives of the current proposed research are: To profile the distribution of 5-hydroxymethylation (5-hmC) in the cardiomyocyte genome of cadaveric cardiac tissue and cardiac biopsy specimens To compare the hydroxymethylome of cadaveric cardiomyocytes with that of cardiac biopsy specimens from HCM (hypertrophic cardiomyopathy) patients and/or cardiac transplant patients (controls) undergoing cardiac catheterization To histologically appraise sarcomere distribution and mitochondrial morphology of cardiomyocytes in the presence of HCM To correlate the mitochondrial genome (mtDNA) with the HCM phenotype To integrate anatomy with biochemistry and genetics and into the instructional design of hypertrophic cardiomyopathy in the core medical curriculum at Mohammed Bin Rashid University (MBRU)

Methods:

Normal and hypertrophic heart specimens will be obtained from 8 whole-body cadavers (n = 8: controls = 2, HCM = 6). Myocardial biopsy specimens will be obtained from Cardiothoracic & Transplant units at Cleveland Clinic in Abu Dhabi, UAE. As this is a proof-of-concept study, we plan to recruit five patients with HCM, where HCM has been diagnosed according to the guidelines of the 2014 ESC Guidelines. Patients with valvular heart disease, history of myocarditis, regular alcohol consumption or cardio-toxic chemotherapy will be excluded. The control biopsy specimens will be obtained from patients who had received heart transplantation. Three investigational approaches will then be employed, viz. i) Gross anatomical evaluation, ii) Histological analysis, and iii) Profiling and analysis of Hydroxymethylome; these investigations will be pursued with minor modification, if required, to standard protocol and in accordance with institutional policy. The objective associated with health professions education will be addressed through a strategy based on the knowledge translation model of Graham (Refer to the text for details).

Results:

The study is yet to commence. Although the funding for this study has been approved by the funding organisation following extensive review.

Conclusions:

The spectrum of cardiovascular diseases has recently received significant focus from the public health sector in the UAE. While HCM is a common familial heart disease, it is now considered to be one of four cardiovascular diseases attributing to the sudden increase in the mortality rate of young Emiratis in the UAE. By incorporating artificial intelligence to identify the epigenetic risk factors associated with HCM; this 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. In summary, the present proposal aims to augment knowledge with regards to epigenetic regulation of HCM, concomitantly strengthening medical education, by integrating genomics education in Anatomy, to stimulate scientific enquiry among medical students thereby providing KT, such that medical students can present new biomedical findings correlating them with known clinical information about the patients’ diseases and traits. While this study will include a small cohort of specimens due to tissue accessibility, it will provide cue to the question “Is there a correlation between epigenetic modification of the genome and HCM phenotype; as well as alluding to the fact if mitochondrial-DNA alterations have detrimental consequences with regards to cardiomyocyte structure-function”. If the investigational approaches employed in this study hint towards a positive correlation, future study of the Hydroxymethylome in a larger cohort of HCM patients will be warranted. Secondly, as cadaver and patient records will provide information regarding other comorbidities (Diabetes, Metabolic syndrome, Dyslipidemia), the underlying effect of these conditions on the severity of HCM may be elucidated, which like above will require confirmation in a larger cohort of patients with HCM. This study will also pave the way to design the strategy of integrating genomics education in anatomy teaching as well as knowledge translation through different frameworks at different levels and competence of medical training. The success of this integration that may be evaluated via different models of feedback (such as that of Pendleton) and structured questionnaires. Clinical Trial: This study is not a clinical trial and therefore doesn't have a trial registration identifier.