Myocarditis is the most common cause of heart failure in children. We investigated viral etiology of myocarditis/dilated cardiomyopathy (DCM) in children and correlated molecular findings with pathologic and clinical data. Polymerase chain reaction (PCR) or reverse transcription (RT)-PCR were used to analyze 59 endomyocardial biopsies from 48 consecutive young (<18 yrs) patients (pts) with clinical and histologic diagnosis of myocarditis and DCM, employing primers designed to amplify specific sequences of various DNA and RNA viruses. Nucleic acids were successfully extracted in 41 pts and viral genomes were found in 20 (49%): 12 out of 26 pts (46%) with myocarditis, 6 out of 13 (46%) pts with DCM, and both patients with endocardial fibroelastosis. Enteroviruses were more common in DCM (72%), whereas adenoviruses and enteroviruses shared the same rate (36%) in myocarditis. The mumps virus genome was detected in the two pts with endocardial fibroelastosis. More diffuse inflammatory infiltrates and myocyte damage as well as more impaired left ventricular end diastolic volume and shortening fraction were noted in viral positive cases. PCR positive pts had a worse outcome, resulting in transplantation or death. Three out of 8 pts with viral myocarditis who underwent cardiac transplantation had recurrent PCR-proven graft viral infection. Viral myocarditis/DCM appeared to be a more severe disease than nonviral forms. Enteroviruses were more common in DCM, whereas adenoviruses were as frequent as enteroviruses in myocarditis. Persistence of viral infection was associated with disease deterioration. Viral myocarditis relapsed after transplantation.
Proinflammatory cytokines, including tumor necrosis factor (TNF)a, have been recognized as important physiopathogenetic factors in the initiation and continuation of inflammatory cardiomyopathies. Experimental and preliminary human studies have demonstrated that TNFa plays a crucial role in enteroviral-induced myocarditis. In this study, we investigated the expression of TNFa and both its receptors (TNFRI and TNFRII) in both viral and nonviral myocarditis. Myocardial expression of TNFa was then correlated with different clinical and pathologic findings. TNFa expression was investigated in endomyocardial biopsies obtained from 38 patients with myocarditis and from eight control subjects by using reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry. Viral etiology was diagnosed by PCR in 20 cases: enterovirus in seven, Epstein-Barr virus in four, hepatitis C virus in three, adenovirus in two, influenza virus in two, cytomegalovirus in one, and double infection adenovirus and enterovirus in one. Immunohistochemistry was also used to analyze both TNFa receptors (RI and RII). A semiquantitative analysis was employed (score 0-3) for necrosis, inflammation, fibrosis and immunohistochemical findings. TNFa mRNA and TNFa protein were significantly more present in viral myocarditis than in nonviral myocarditis (16/20 vs 3/18, P ¼ 0.001). Remarkable immunostaining was observed for both receptors, particularly TNFRI. Histological analysis revealed that myocardial necrosis (mean score 1.89 vs 1.15, P ¼ 0.01) and cellular infiltration (mean score 2.26 vs 1.78, P ¼ 0.05) were more prominent in TNFa-positive cases. Among TNFa-positive cases, the greater TNFa mRNAs, the more impaired was cardiac function. Our findings suggest that the expression of TNFa may play an important role in the pathogenesis of viral myocarditis of any etiology and may influence the severity of cardiac dysfunction. Cytokine effects are more strictly linked to overexpression of TNFRI.
Objective: To compare active (AM) with borderline (BM) myocarditis to verify whether the pathological distinction between the two forms may help to identify patients with different clinical and haemodynamic characteristics and to aid prognosis. Materials: Myocarditis was diagnosed in 56 patients on endomyocardial biopsy (EMB) within one year from clinical onset of the disease between 1991 and 1998. Fourteen patients were excluded because of a lack of adequate and complete information. EMBs and clinical records of the 42 remaining patients were reviewed. Immunohistochemistry on bioptic samples was regularly performed. Polymerase chain reaction (PCR) for a panel of viruses was performed in 23 patients (55%). Clinicopathological correlations were calculated.
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