Fever of unknown origin (FUO) is a diagnosis that describes a prolonged febrile illness without an established cause, despite investigations. From the first definition of the medical condition (given by Petersdorf and Beeson in 1961) the diagnostic criteria have changed over time, intending to improve the management and outcome of these patients. The main causes of FUO fall into 4 categories: infectious, non-infectious (inflammatory), neoplastic and diverse causes. The etiology of FUO has changed over time, due to ever-changing disease patterns and the development of diagnostic techniques. A significant percentage of patients with FUO remain without an etiologic diagnosis, despite advanced diagnostic tests. Gathering potentially diagnostic clues through history, physical examination and nonspecific key paraclinical abnormalities is the basis for the diagnosis of FUO.
Two major trials, EMPA-REG OUTCOME trial (with Empagliflozin) and CANVAS trial (with Canagliflozin) have demonstrated the beneficial effects of SGLT2 inhibitors in patients with type 2 diabetes at risk for heart failure. SGLT2 inhibitors possess a unique pharmacological profile and have shown a significant reduction of hospitalization for heart failure in diabetic patients, immediately after treatment commencement. It seems that their effects are beneficial both in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. SGLT2 inhibitors reduce cardiovascular endpoints in patients with diabetes and high cardiovascular risk, most likely through a reduction of heart failure-related events. Empagliflozin treatment exerts beneficial effects on vascular function and central haemodynamics. Various mechanisms seem to contribute to the beneficial effects of SGLT2 inhibitors in heart failure. Taking into consideration their cardiovascular benefits and the number of ongoing trials with these drugs, there is a possibility to expand their indication to nondiabetic patients with heart failure. This review focuses on the newest insights into the beneficial effects of SGLT2 inhibitors on the cardiovascular system.
