Aspergillus Endocarditis in Native Valves in Non-Traditional Hosts: A Systematic Review of a Case in a Patient with CREST Syndrome and Advanced Liver Cirrhosis

<b>Background</b>: <i>Aspergillus</i> endocarditis is a rare but life-threatening form of infective endocarditis that typically occurs in patients with a history of cardiac surgery, prosthetic valve implantation, or profound immunosuppression. Native valve involvement in non-traditional hosts remains exceptionally rare and is diagnostically challenging. <b>Case presentation</b>: We describe a 56-year-old woman with CREST syndrome and advanced liver disease awaiting transplantation who developed native aortic valve endocarditis. Blood cultures and serum biomarkers (galactomannan and β-d-glucan) were also negative. Transthoracic echocardiography revealed vegetation on the aortic valve. Valve replacement was performed, and <i>Aspergillus fumigatus</i> was isolated from two valve cultures. Liposomal amphotericin B was initiated; however, the patient died of multiorgan failure two weeks later. <b>Systematic review</b>: To contextualise this case, we conducted a systematic review of the literature following the PRISMA guidelines. We included microbiologically confirmed cases of native valve <i>Aspergillus</i> endocarditis based on valve or embolic tissue analysis. Forty-three studies met the inclusion criteria, comprising 45 patients in total. Data were independently extracted by two reviewers and narratively synthesised due to clinical heterogeneity. <b>Conclusions</b>: This case illustrates the diagnostic and therapeutic challenges of native-valve <i>Aspergillus</i> endocarditis in patients without classical risk factors for the disease. Early imaging and a high index of suspicion are crucial for diagnosis. Combined surgical and antifungal therapy remains the cornerstone of management, although the mortality rate remains high.