Basic Science Aspects of the Pathogenesis of Infective Endocarditis

As a serious and frequently lethal condition whose incidence is rising, infective endocarditis remains a challenging condition, and its underlying mechanisms deserve continued investigation. The diverse organisms that cause infective endocarditis, as well as the many predisposing cardiac conditions and varying scenarios that present in the clinic, may suggest that specific pathogen attributes and/or interactions with the immune system would lead to idiosyncratic disease mechanisms and pathways. However, the formation of vegetations, a major manifestation of infective endocarditis, appears to utilize a shared mechanism that is relevant to understanding the resulting cardiac tissue damage and distant embolism. An initial insult to the endocardial surface of the heart, particularly of the valves, together with exposure to an invasive pathogen or under the right conditions, an opportunistic commensal, leads to a coordinated response from endothelial cells, the innate immune system, and prothrombotic pathways. These responses undoubtedly contain the infection, but they also sustain it and render it indolent. The resulting vegetation is now known, from recent proteomic, imaging, and biochemical studies, to have the hallmarks of an infected, consolidated thrombus. Extensive proteolytic activity in vegetations may promote their growth and contribute to local tissue destruction, as well as to vegetation fragility and embolism.