Inflammatory Heart Diseases

 

Myocarditis and inflammatory dilated cardiomyopathy

Inflammation of the myocardium, myocarditis, could be caused by many different agents, bacterial, rickettsial, mycotic, protozoan, and viral. Clinical presentation of the disease is highly variable, ranging from nonspecific flu-like symptoms, arrhythmias, palpitations, dizziness, and syncope, to left ventricular failure. Echocardiography, scintigraphy, contrast-enhanced MRI, serum creatinine kinase and troponin T and I levels are helpful in making the diagnosis of myocarditis. For a definitive diagnosis, biopsy of the myocardium is required. The diagnosis of myocarditis is based on the presence of mononuclear infiltration and cardiomyocyte necrosis using Dallas criteria. The American Heart Association, the American College of Cardiology, and the European Society of Cardiology summarized clinical scenarios when an endomyocardial biopsy should be performed, and emphasized the usefulness of biopsy in establishing the diagnosis of myocarditis in certain clinical settings. Based on the character of the heart infiltrate, different types of myocarditis are recognized such as lymphocytic, borderline, granulomatous, giant cell, and eosinophilic 6% .It is recognized now that around 9-16% of patients with myocarditis progress to dilated cardiomyopathy (DCM). DCM is characterized by chronic left and right ventricular dilatation with normal or reduced left ventricular wall thickness and impaired contraction. DCM is the major cause of heart failure in individuals below the age of 40 and a major indication for cardiac transplantation. The 5-year survival rate of patients with DCM is less than 50%. Cardiac transplant-free survival in a pediatric population with DCM is less than 60%. Currently, no drugs are available to delay or arrest progression to DCM, or improve the long term survival of these patients.

 


 

Myocarditis and dilated cardiomyopathy animal models

The most persuasive evidence that some forms of myocarditis are driven by autoimmune processes comes from animal models. Widely used are Coxsackie virus B3 induced mice models. The first model is notable by acute viral myocarditis and sudden death in the majority of animals within a week of infection. The second model is based on using the heart-passaged CVB3 virus with mild viral myocarditis in all mice strains and with susceptible mice strains progressing to chronic myocarditis. The chronic autoimmune phase of CVB3-myocarditis can be replicated in a model of experimental autoimmune myocarditis (EAM) by immunizing susceptible mice strains with cardiac myosin or myocarditogenic peptide derived from the alpha cardiac myosin heavy chain emulsified in complete Freund’s adjuvant (CFA). Myosin-induced EAM and DCMI are independent of viral infection and are induced by immunization with cardiac myosin and CFA or by immunization with an H2d-restricted peptide derived from the cardiac myosin heavy chain alpha sequence (MyHCa614–629). The most prevalent leukocytic population in the hearts of WT mice during chronic phase of CVB3-myocarditis and EAM are monocytes/macrophages, mirroring giant cell myocarditis.