Cardiac Defect of Hypertrophic Cardiomyopathy Aggravated By Life Stresses

Sakthivel Sadayappan, PhD, MBA Associate Professor Department of Cell and Molecular Physiology Loyola University Chicago Health Sciences Division Maywood, IL  60153-5500, USA.MedicalResearch.com Interview with:
Sakthivel Sadayappan, PhD, MBA
Associate Professor Department of Cell and Molecular Physiology
Loyola University Chicago Health Sciences Division
Maywood, IL  60153-5500, USA.

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Sadayappan: Hypertrophic cardiomyopathy (HCM) is the most common form of genetic heart defect, affecting 1 in 500 people in the general population. HCM results in excessive thickening of heart muscle without an obvious cause, such as hypertension or exercise stress. Often, HCM results in sudden cardiac arrest as a result of cardiac arrhythmia. Electrocardiogram, echocardiogram and cardiac magnetic resonance imaging are commonly used to diagnose HCM. However, genetic defects in more than 10 genes could also cause HCM, and standard screening for these genes is readily available. Notwithstanding our ability to diagnose the disease, a major challenge arises from its heterogeneity. That is, individuals with the same genetic defect often present with different symptoms, ranging from no symptoms at all to severe heart enlargement. Therefore, treatment options vary from person to person, and, at present, no permanent cure is available for HCM. Beta-blockers, calcium antagonists and anti-arrhythmic drugs are currently being used to manage the disease. However, scientists must discover the reasons that explain why some people experience more severe symptoms than others.

In today’s modern world, people are afflicted with stresses including, for example, diabetes, hypertension, hyperlipidemia (high cholesterol), and alcoholism. Therefore, we have hypothesized that additional cardiac stresses can aggravate the onset of Hypertrophic cardiomyopathy. To prove our hypothesis, we used a mouse model having a genetic defect known to affect cardiac muscle contractility. We subjected these mice to severe cardiac stress over a period of 12 weeks. Compared with normal mice, we found that the mutant mice showed significant cardiac abnormalities, including those associated with HCM. Thus, this demonstrated, for the first time, that additional cardiac stress applied in the presence of known genetic defects exacerbates the onset of HCM.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Sadayappan: From a clinical standpoint, patients with Hypertrophic cardiomyopathy need to be evaluated for risk factors, such as diabetes, hypertension, obesity, hyperlipidemia, alcoholism, and others, and managed accordingly. Knowing family history is also critical to the management of HCM, as is educating the general public.

From the patient’s point of view, changing lifestyle is essential. Proper diet and exercise should be formulated and followed systematically. Other family members should be screened for the presence of genetic defects and should have regular physical checkups, starting early in life. Several programs are in place to identify risk for sudden cardiac death and to increase awareness of this issue among high school students (American Heart Association).

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Sadayappan: Future research studies should determine the exact pathways and molecular mechanism that will explain the cause of . This naturally leads us in the direction of genetic engineering, and one avenue of investigation involves, for example, the generation of induced pluripotent adult stem cell (iPSC)-derived cells, in this case, cardiomyocytes, for therapeutic applications or use in diagnostic screening.

Citation: Barefield D, Kumar M, Gorham J, Seidman JG, Seidman CE, de Tombe PP, Sadayappan S. Haploinsufficiency of MYBPC3 exacerbates the development of hypertrophic cardiomyopathy in heterozygous mice. J Mol Cell Cardiol. 2014 Nov 25;79C:234-243. doi: 10.1016/j.yjmcc.2014.11.018. [Epub ahead of print]

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Last Updated on January 7, 2015 by Marie Benz MD FAAD