Challenges and Opportunities in Pediatric Heart Failure and Transplantation

115 Myocarditis has been defined by the World Health Organization/International Society and Federation of Cardiology as an inflammatory disease of the heart muscle diagnosed by established histological, immunologic, and immunohistological criteria. Insights into its clinical manifestation and treatment in both adults and children have been the subject of a number of recent reviews. It is caused primarily by numerous infectious agents, but it may also accompany autoimmune disease, hypersensitivity reactions, and toxins (Table 1). In North America and developed countries, it primarily has a viral origin. In Central and South America, Trypanosoma cruzi (Chagas disease) is a common cause. Diphtheria often causes myocarditis in countries without widespread immunization. Although enteroviruses have classically been identified as the prime viral agent, new techniques to extract viral genome from myocardium with polymerase chain reaction techniques have in both children and adults revealed previously unrecognized viruses such as adenovirus, parvovirus B19, human herpesvirus 6, hepatitis C, Epstein-Barr virus, and cytomegalovirus. Interestingly, the pattern of identified viral pathogens in myocarditis has evolved over the last 20 years from enteroviruses and adenoviruses to primarily parvovirus and herpesvirus 6. Endomyocardial fibroelastosis, a once frequent cause of infantile dilated cardiomyopathy that is now rarely seen, was linked to the mumps virus via viral polymerase chain reaction analysis of archived pathological sample, suggesting that its reduced prevalence might be attributed to immunization. In a somewhat confusing fashion, the American Heart Association’s contemporary definitions of cardiomyopathies classify myocarditis as an inflammatory cardiomyopathy but also lists the same infectious causes of dilated cardiomyopathy as those found with myocarditis. This conundrum typifies myocarditis. Its myriad presentations range from minimal symptoms to severe heart failure and sudden death. It is commonly associated with typical abnormalities observed in ECGs, cardiac imaging, and cardiac biomarkers, but it may exist in the absence of those abnormalities. It is a disease defined by observable myocardial pathology but may be present despite normal-appearing cardiac biopsies. Immunosuppression and immunomodulation have been used to treat myocarditis in children for >20 years, but their use remains controversial. These variations and controversies make the diagnosis and treatment of myocarditis in children a fascinating challenge and are the subject of this report.