Bacterial Infiltration of Structural Heart Valve Disease

 

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Introduction: The pathology of structural heart valve disease (sVHD) ranges from rheumatologic basic diseases to chronic degenerative rebuilding processes after acute bacterial infections. Basically, the detection of pathogens based on microbiological standard methods. In the last 2 decades molecular biology methods have been investigated, which allow to detect the microbial spectrum in heart valve tissues independently of microbiological cultivation. In particular, total gene analysis is a sensitive and highly specific analytical method which discloses a deeper insight in the pathogenicity of the diseases. In the present study it was examined whether a pathogen spectrum similar to that of acute infectious endocarditis aIE can be detected in the heart valve tissue of patients with sVHD.

Method: From a prospective cohort (March 2016 to April 2017) of 203 patients with sVHD and 46 patients with aIE, 6 patients with sVHD and/or aIE were selected randomly. The underlying heart valve disease was examined by clinically, histopathologically and microbiologically examination. In addition to immunohistological structural analysis, the bacterial metagenome of the heart valve tissue was determined by using of HiSeq technology platform. The virulence potential of the bacteria was determined by assigning specific genome sequences to virulence factors.

Results: The histopathology of heart valve tissue is the key to discriminate between acute and chronic disease and consequently is important for the therapy options. In the aIE cohort, Microbiology and immunostainings yielded bacteria such as Staphylococcus, Enterococcus and Streptococcus. Interestingly, also the microbiological examinations of the heart valves of 2 sVHD patients revealed Clostridium difficile and Enterococcus faecalis. Subsequent total genome analysis of heart valve tissue reveals up to 8 different bacterial species in 3 patients with sVHD and no germ detection in 3 patients with sVHD. In comparison, up to 15 different bacteria per patient could be detected in all heart valves of the aIE cohort.

Conclusion: The metagenome analysis is a valid technology platform to generate new insights into the pathophysiology of sVHD in contrast to aIE. Histopathological examinations of all heart valve tissues are indispensable for discrimination between acute and chronic infections. Our results suggest that sVHD may be triggered by chronic inflammation or influenced by secondary bacterial infiltration.