The study aimed to analyze outcomes of surgery for blood culture-negative infective endocarditis (BCNIE) and to evaluate the role of molecular biological imaging. Patients undergoing surgery for native or prosthetic valve endocarditis from 2013 to 2022 were analyzed regarding blood culture-positive infective endocarditis (BCPIE) and BCNIE. For laboratory diagnostics in BCNIE, excised valves or prostheses underwent conventional microbiological culture and fluorescence in situ hybridization combined with 16S rRNA-gene polymerase chain reaction and sequencing (FISHseq). Of 521 patients overall, we identified 473 patients (342 males, mean age 63 ± 14.4 years) with preoperative blood cultures: 396 with BCPIE (83.7%) and 77 with BCNIE (16.3%).Preoperative characteristics and operative procedures were comparable between groups and the calculated perioperative risk (EuroSCORE II) was identical (BCNIE: 12.2 ± 8.8%, BCPIE: 12.9 ± 11.9%, p = 0.788). At surgery, signs of infective endocarditis were present in 71%, missing in 18%, and inconclusive in 10% of patients with BCNIE. While valve cultures alone identified pathogens in 32% of BCNIE patients, the combination with FISHseq confirmed the infective etiology in 98% and identified causative pathogens in 52%. Overall, early mortality was similar in BCNIE (16.9%) and BCPIE (18.2%, p = 0.620), but increased in 37 BCNIE patients without pathogen identification compared to 40 patients with pathogen identification (27.0% versus 7.5%, p = 0.032). Integrating FISHseq as molecular biological imaging technique into valve analysis algorithms in patients undergoing surgery for BCNIE increases diagnostic gain and potentially improves outcome.
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