Oyere Onuma

Date of Award

4-9-2008

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Forrester Lee

Abstract

The aim of this project is to develop a noninvasive serum test that predicts histologic forms of myocarditis (inflammatory) and dilated (non-inflammatory) cardiomyopathy using proteomic techniques to analyze serum proteins. Idiopathic dilated cardiomyopathy (DCM) and myocarditis (myocardial inflammation) represent a spectrum of heart muscle disease of various etiologies that usually present with progressive heart failure. Together, they constitute the leading cause of heart transplantation in the United States. Currently, the gold standard of diagnosis of myocarditis is by endomyocardial biopsy (EMB) and histopathological classification according to the Dallas Criteria ; however this diagnostic technique is severely limited by its invasiveness, a lack of sensitivity and an attendant sampling error, yielding diagnostic information in only 10-20% of the cases . As such, the development of a non-invasive highly specific test for myocarditis is of great value and importance particularly in the diagnosis of giant cell myocarditis, a rare but very fulminant form of autoimmune myocarditis where timely institution of appropriate immunosuppressive therapy significantly increases transplant-free survival. We proposed, using an observational case-control study, to undertake a proteomic analysis to compare serum proteomic profiles - determined by mass spectroscopy and isotope tagging- with histologic findings on endomyocardial biopsy. Our hypothesis is that different forms of myocarditis and dilated cardiomyopathy have distinct serum protein profiles and that these unique profiles which correlate with specific histologic types, will allow for noninvasive diagnosis of major forms of myocarditis and DCM.

Comments

This is an Open Access Thesis.

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