Date

9-2020

Department

School of Health Sciences

Degree

Doctor of Philosophy

Chair

David DeWitt

Keywords

Cardiovascular Disease, Heart Disease, Cadaver

Disciplines

Anatomy | Biology

Abstract

For nearly a century, heart disease has been the leading source of death and disease in the United States, causing the deaths of hundreds of thousands of individuals every year and burdening millions more with diminished health and severe disability. However, despite the significant known prevalence of heart disease, studies suggest that many more individuals—and particularly those within the female and elderly populations—may possess undiagnosed heart disease which remains undetected even after death due to the lack of autopsy examination. In the absence of autopsy, many cases of heart disease may never be identified, resulting in a skewed understanding of disease burden which may hinder improvements in diagnosis and treatment of heart disease. This may also impair accurate detection of high-risk individuals who are unknowingly susceptible to infectious diseases such as influenza, pneumonia, or—a more current concern—the recently discovered novel coronavirus-19. In addition, heart disease often carries strong genetic components, making it vital that undiagnosed heart disease be identified so that family members can likewise be made aware of their risk.

In order to identify the prevalence of undocumented heart disease in the absence of autopsy examination, 50 cadaveric donor hearts were examined, and findings were compared with documented prevalence according to donor medical records. Results revealed that whereas only 30% possessed documented forms of heart disease, features consistent with mild to severe forms of heart disease were observed in 98% of donors. Since most of these donors were elderly, this suggests that the vast majority of the elderly population likely possesses mild to severe forms of heart disease. Undocumented heart disease was particularly prevalent in the female population, with 50% of female donors displaying undocumented features of heart disease in the absence of any documented form of CVD (heart disease or otherwise), although undocumented heart disease in the absence of documented CVD was also observed in 36% of male donors.

Since cadaveric tissue has not previously been utilized for gene expression studies, an RNA extraction protocol was modified for embalmed tissue in order to identify genetic risk factors potentially associated with these undocumented cases of heart disease. This protocol yielded amplifiable RNA of sufficient yield and purity for microarray analysis. While the extent of RNA degradation varied between samples, microarray analysis revealed over 6,000 unique mRNA transcripts consistently detected in all cadaveric samples, including a wide variety of transcripts known to be associated with heart disease.

This study is the first to identify the significant prevalence of undocumented heart disease in cadaveric donors and suggests that many forms of heart disease remain undiagnosed in the absence of autopsy, particularly in the elderly and female populations. This study is also the first to utilize embalmed cadaveric tissue for the purpose of gene expression studies. This technique will potentially provide unprecedented opportunities for genomic studies related to disease etiology within cadaver donors and allow for the identification of genetic risk factors which may have been passed on to family members. Collectively, these findings can be utilized to gain a more accurate understanding of heart disease burden within the population, potentially facilitating the identification of high-risk individuals and reducing the fatal effects of heart disease in those unaware of their risk.

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