Clinician Scientist-Programm 2022

Thema: "Outcome analysis and metabolomics biomarker study in patients with acute myocarditis (METACARDITIS)"

Zusammenfassung:
Myocarditis is an underdiagnosed disease with an incidence of about 1:10,000 and around 3,500 cases requiring hospitalization per year in Germany. The health care cost in Germany is more than three billion euro per year. It is estimated that 10-15% of patients with prior myocarditis develop cardiomyopathy and heart failure. Infection and inflammation renders the heart vulnerable to structural and functional abnormalities that lead to cardiomyopathies and heart failure. Thus, early and specific diagnosis of myocarditis is important in preventing irreversible cardiac damage and failure. Myocarditis is an inflammation of the heart muscle due to the infiltration of the heart with inflammatory cells leading to structural and functional damage with irreversible loss of cardiomyocytes. It could result from non-infectious causes such as autoimmune, pharmacotherapy-associated, giant cell myocarditis, eosinophilic myocarditis and sarcoidosis. Infectious causes include infection with cardiotropic pathogens (viruses, bacteria, parasites or fungi) or systemic infection in bacteremia or sepsis. The prognosis of myocarditis depends on pathology and extent of cardiac damage. Diagnostic approaches include clinical assessments and noninvasive cardiac imaging such as MRI and echocardiography. The gold standard using pathologic techniques is invasive myocardial biopsy through puncture of the femoral or jugular vein with risk of perforation, bleeding, infection and death. Although Immunohistochemistry of biopsy specimens is the most reliable technique for detection of immune cells and myocarditis, cardiac biopsy is highly invasive and limited to specific areas of the heart. Thus, non-invasive techniques for detection of inflammation and myocarditis are warranted and potentially superior to this gold standard. Local infection is associated with shedding or secretion of e.g. viral particles into the circulation; thus, it is possible to detect pathogen-specific signatures in blood of patients using state-of-the-art deep sequencing which might detect metagenomics markers. With development of non-invasive diagnostics for the characterization of myocarditis and definition of sensitive markers, chip-based tests could be developed for a time- and resource-sparing approach to diagnosing myocarditis with high sensitivity and specificity. There exists already preliminary data on proteomic analysis of myocardium and in circulation in patients with myocarditis. And it has been shown that inflammatory and lipidomic markers are most affected in myocarditis. This project is a subproject of a larger study (Metasequencing and non-genomic biomarkers for diagnosis of infectious myocarditis: METAsequencing for diagnosis of myoCARDITIS - METACARDITIS). We aim to address the potential for an early non-invasive diagnosis of specific forms of myocarditis based on circulating metabolomic and proteomic markers using metabolomic techniques of blood-derived samples and to test the potential of blood-based testing for replacing the invasive technique of myocardial biopsies. We would use serum samples and endomyocardial biopsies from a large cohort of patients with myocarditis for the analysis.