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Background: Infective endocarditis (IE) is an uncommon but potentially fatal disease, with an incidence of 13.8 per 100 000 and persistent high mortality (15-30%). In 10-20% of cases, cultures remain negative and additional serological testing for infectious and non-bacterial endocarditis is required. Case summary: We report a case of a 25-year-old North African man with a history of lupus nephritis presenting with progressive dyspnoea, retrosternal pain, and fever. Transthoracic echocardiography showed extensive calcifications on the aortic valve with severe aortic regurgitation. Prior echocardiograms had already documented a large aortic valve calcification, which was not considered suspicious for IE on previous FDG-positron emission tomography scan. However, a transoesophageal echocardiogram at admission revealed a functional bicuspid aortic valve with a large vegetation and severe left ventricular dysfunction. The patient rapidly deteriorated into beginning cardiogenic shock, necessitating emergency mechanical aortic valve replacement. Blood cultures remained negative, but serology testing revealed elevated Discussion: This case illustrates the diagnostic challenges of BCNIE. Serologic and molecular testing should be pursued when cultures remain negative. Multi-disciplinary management, early surgical intervention, appropriate antibiotic treatment, and optimized heart failure therapy in IE presenting with acute heart failure can improve patient outcomes.