Cerebral Thrombus Analysis in Infective Endocarditis: Unveiling Composition for Diagnostic Insight

ABSTRACT Background and Aims Infective endocarditis (IE) is a life-threatening condition known to cause stroke. Swift diagnosis and antibiotic treatment are crucial for preventing cerebral and systemic embolism, therefore reducing mortality and morbidity. However, diagnosing IE can be challenging. In this study, we aimed to assess whether analyzing cerebral thrombi retrieved by endovascular thrombectomy from stroke patients with IE could aid in the diagnosis and shed light on the composition signature of endocarditic thrombi. Methods We compared cerebral thrombi from three groups of ischemic stroke patients: those with definite infective endocarditis (IE) (n=10), those with cardioembolic stroke and concomitant infections other than IE (n=10 CE-I + ), and those with cardioembolic stroke without infections (n=30 CE-I - ). Our multiparameter analysis encompassed histological examinations, molecular biology and microbiological tests to detect microorganisms within the thrombi and to comprehensively assess their structural composition and immune signatures. Results We directly detected invading pathogens through histology or PCR in all cerebral thrombi from IE patients, while none of the control thrombi exhibited such pathogens. Thrombi from IE patients displayed a distinct composition, characterized by a significant lower content of red blood cells, reduced CD14+ monocytes, increased von Willebrand Factor density, and a cell-dominant pattern of Neutrophil Extracellular Traps (NETs) deposition. Conclusions Comprehensive analysis of cerebral thrombi from stroke patients with suspected IE sustains early, definitive endocarditis diagnosis by detecting pathogens and immunothrombotic changes.