Pathophysiology and Aetiological Diagnosis of Inflammatory Myocardial Diseases with a Special Focus on Parvovirus B19

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Abstract
Inflammatory processes induced by viral or bacterial infections are believed to be one of the major pathogenetic mechanisms in myocardial diseases. Although the reason for progression to myocardial failure is not fully understood, postulated mechanisms include persistent viral infection alone or in combination with autoimmune processes. A variety of cardiotropic viruses have been identified to elicit myocarditis, with enteroviruses and adenoviruses as the most frequent causative agents in children and adolescents. However, parvovirus B19 (PVB19) has recently emerged as another potential pathogen in adult patients associated with inflammatory heart disease. Many dimensions of inflammatory heart disease coexist while different phases of the disease progress simultaneously: phase 1 is dominated by viral infection, phase 2 by the onset of (probably) multiple autoimmune reactions, and phase 3 by the progression to cardiac dilatation without the role of an infectious agent and cardiac inflammation. Taking these mechanisms into account, screening for viral and bacterial genome by polymerase chain reaction (PCR) and detection of inflammatory infiltrates by immunohistochemistry are considered crucial for establishing an aetiological diagnosis, thereby allowing initiation of specific therapeutic strategies. In a large cohort of 3345 consecutive patients with left ventricular dysfunction evaluated over a period of 10 years, prevalence of PVB19, coxsackievirus (CVB), human cytomegalovirus (HCMV), influenza A virus and adenovirus (ADV) genome was assessed by PCR. Inflammatory infiltrates within the myocardium were detected by immunohistochemistry according to the WHF criteria and by histopathology according to the Dallas criteria of myocarditis. For control, endomyocardial samples of patients with arterial hypertension were studied. Parvovirus B19 was the most often detected virus in all patient subgroups, with positivity ranging from 17% to 33%. Except for PVB19, CVB RNA (3%), ADV (2%) and CMV (3.9%) were the most frequently detected viral genomes. Interestingly, detection of PVB19 genome was significantly correlated with inflammatory heart disease and reduced ejection fraction. Importantly, an aetiological diagnosis requires the immunohistochemical and molecular biological investigation of endomyocardial biopsies. Such an approach may change the management of these diseases in the future. One of the aims of the study was to reveal the underlying dominant pathophysiological mechanisms in a for deciding on the most approriate therapy.