Unexpected Infective Endocarditis: Towards a New Alert for Clinicians.

Despite the clear indications and worldwide application of specific guidelines, the recognition of Infective Endocarditis (IE) may be challenging in day-to-day clinical practice. Significant changes in the epidemiological and clinical profile of IE have been observed, including variations in the populations at risk and an increased incidence in subjects without at-risk cardiac disease. Emergent at-risk populations for IE particularly include immunocompromised patients with a comorbidity burden (e.g., cancer, diabetes, dialysis), requiring long-term central venous catheters or recurrent healthcare interventions. In addition, healthy subjects, such as skin-contact athletes or those with piercing implants, may be exposed to the transmission of highly virulent bacteria (through the skin or mucous), determining endothelial lesions and subsequent IE, despite the absence of pre-existing at-risk cardiac disease. Emergent at-risk populations and clinical presentation changes may subvert the conventional paradigm of IE toward an unexpected clinical scenario. Owing to its unusual clinical context, IE might be overlooked, resulting in a challenging diagnosis and delayed treatment. This review, supported by a series of clinical cases, analyzed the subtle and deceptive phenotypes subtending the complex syndrome of unexpected IE. The awareness of an unexpected clinical course should alert clinicians to also consider IE diagnosis in patients with atypical features, enhancing vigilance for preventive measures in an emergent at-risk population untargeted by conventional workflows.