Title: Infectious agents in the myocardium of patients with dilated cardiomyopathy: idiopathic, chagasic, ischemic and other etiologies
Abstract: Purpose: Clinical and experimental studies suggest an association between infectious agents and idiopathic dilated cardiomyopathy (DCM), but other data question this relation. The aim of this study was to investigate the presence of infectious agents in endomyocardial biopsy (EMB) specimens of patients with idiopathic DCM and other specific etiologies, compared to a control group of heart donors. Methods and results: Between 2008 and 2011 were studied EMB specimens from hospitalized patients with idiopathic DCM in evaluation for heart transplantation, donors and explanted hearts from different etiologies. 2 groups were defined: donors (29 cases) and DCM (55 cases, including 32 with idiopathic DCM, 9 chagasic, 6 ischemic and 8 other etiologies). Were studied by immunohistochemistry: enterovirus, adenovirus, herpes simplex, Epstein-Barr virus (EBV), parvovirus B19 (PB19), HHV6, hepatitis B and C, mycoplasma, chlamydia and borrelia. Results were presented as median, interquartile range p25, p75 (percentage of positive area), and comparison between donors and DCM were made by Mann Whitney U test. There were an increased expression of enterovirus antigens in donors compared to DCM [2 (0.56 to 5.7) x 0.61 (0.28 - 2.45), p = 0.0075] and increased expression of hepatitis C antigens [1.31 (0.5 to 3.6) x 0.6 (0.37 - 1.41), p = 0.02] in DCM compared to donors. By molecular biology, were investigated: adenovirus, EBV, cytomegalovirus (CMV), HHV6, PB19, mycoplasma, chlamydia and borrelia. The results were presented by percentage of genome positivity, and comparison between groups were made by qui-square and Fisher's exact tests. There was a high genome positivity of microorganisms, including co-infections, with higher positivity in donors comparing to DCM for adenovirus (83.3% vs. 58.7%, p = 0.035) and HHV6 (86.4% vs. 49%, p = 0.0015). To our knowledge, this study is pioneer demonstrating the presence of virus genome in cardiac tissue of chagasic DCM (adenovirus 55%, EBV 40%, CMV 20%, HHV6 75%, PB19 57%). Conclusion: The presence of infectious agents in the myocardium of patients with idiopathic DCM is frequent, and similarly in donors and DCM from other etiologies, including ischemic and chagasic. Based on our results the causal relationship between the presence of infectious agents in cardiac tissue and the development of DCM is controversial. Additional studies are needed to determine the real role of infectious agents in the pathogenesis of DCM.