SEROLOGICAL AND MOLECULAR EVIDENCE OF ENTEROVIRUS INFECTION IN PATIENTS WITH END-STAGE DILATED CARDIOMYOPATHY

Objective - To study the relative diagnostic value of enterovirus-spec ific molecular biological and serological assays in patients with end- stage dilated cardiomyopathy, and to investigate the possible role of other cardiotropic viruses in dilated cardiomyopathy. Design - Analysi s of recipient myocardial tissue and serum from patients with dilated cardiomyopathy and controls undergoing cardiac transplantation for end -stage cardiac disease. Setting - University virology department and t ransplantation unit. Methods - Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis of myocardial RNA and DNA; e nterovirus-specific in situ hybridisation; enterovirus-specific immuno globulin M detection. Results - Enterovirus RNA was detected in myocar dial tissue from only a small proportion of (five of 75) hearts. Howev er, although enterovirus-specific immunoglobulin M responses were dete cted in 22 (28%) of 39 controls patients, a significantly higher preva lence was observed among patients with dilated cardiomyopathy (22 (56% ) of 39 patients; P < 0.005). All enteroviruses detected in myocardium showed greatest nucleotide sequence homology with coxsackievirus type B3. Detection of enterovirus RNA in myocardium by the polymerase chai n reaction and by in situ hybridisation gave comparable results. Other potentially cardiotropic virus genomes, including human cytomegalovir us, influenzaviruses, and coronaviruses were not detected in myocardiu m. Conclusion - This study found that enterovirus-specific immunoglobu lin M responses provided the strongest evidence of enterovirus involve ment in patients with end-stage dilated cardiomyopathy. However, the h igh background prevalence of these responses limits their diagnostic v alue. The finding that enteroviruses detected in myocardium were coxsa ckievirus type B3 accords with recent findings in patients with acute myocarditis, and indicates that this serotype is the major cardiotropi c human enterovirus.