Tropheryma whipplei: A Cause of Rapidly Fatal Prosthetic Valve Endocarditis Despite a Classically Indolent Disease Course.

BACKGROUND: Tropheryma whipplei (T. whipplei) is a rare cause of culture-negative infective endocarditis and may present without classic gastrointestinal manifestations, leading to delayed diagnosis and severe valvular destruction. CASE SUMMARY: A 76-year-old man with a prior bioprosthetic aortic valve replacement presented with at least 2 weeks of fatigue, generalized weakness, intermittent chills, and worsening dyspnea, along with approximately 8 kg of unintentional weight loss since the preceding summer; he remained afebrile. Blood cultures remained persistently negative. Transesophageal echocardiography revealed a > 3-cm vegetation, prosthetic valve dehiscence, severe paravalvular regurgitation, and periannular abscess. Despite empiric broad-spectrum antibiotics and urgent surgical evaluation, the patient deteriorated and suffered cardiac arrest. Whole-blood polymerase chain reaction testing collected during hospitalization returned positive for T. whipplei after the patient's death, establishing the diagnosis. DISCUSSION: Whipple endocarditis typically presents as culture-negative disease and often lacks systemic features, delaying recognition. This case highlights the diagnostic challenge posed by T. whipplei in prosthetic valve endocarditis and the value of molecular testing when conventional cultures remain negative. TAKE‐HOME MESSAGE: Early PCR testing should be considered in culture-negative prosthetic endocarditis, as it may establish a diagnosis when conventional cultures and valve tissue are unavailable.