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Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number of intravascular and intracardiac procedures associated with device implantation, the number of patients at risk is growing too. If bacteremia develops, infected vegetation on the native/prosthetic valve or any intracardiac/intravascular device may occur as the final result of invading microorganisms/host immune system interaction. In the case of IE suspicion, all efforts must be focused on the diagnosis as IE can spread to almost any organ in the body. Unfortunately, the diagnosis of IE might be difficult and require a combination of clinical examination, microbiological assessment and echocardiographic evaluation. There is a need of novel microbiological and imaging techniques, especially in cases of blood culture-negative.
IE of the left-sided native valve should be suspected in patients with relevant cardiac risk factors (e.g., pre-existing valvular or congenital heart disease), prior IE and other predisposing conditions, including intravenous drug use, immunosuppression, recent dental or surgical procedure, an indwelling cardiac device or intravenous catheter. Positive blood cultures, clinical features and echocardiographic findings remain the cornerstones for left-sided native valve IE’s diagnosis. At least three sets of blood cultures should be obtained at 30 min intervals from separate venipuncture sites before starting antibiotic therapy [31][32]. Each set consists of one aerobic and one anaerobic bottle, each of which contains a volume of blood of 10 mL. Samples from peripheral veins using a meticulous sterile technique are preferred over central venous catheter due to the risk of contamination. As bacteremia is usually continuous in patients affected by IE, blood cultures can be collected at any time and not necessarily when fever or chills occur. Blood culture results should be interpreted according to the modified Duke’s criteria. Most clinically significant bacteremias are usually detected within 48 h; the pathogen members of the HACEK group can be identified after 5 days of incubation with modern detection systems [33]. Occasionally, false-positive blood cultures can occur, due to the presence of contaminants. Contamination likelihood is reduced when the microorganism is found in multiple blood cultures obtained from different venipuncture sites [34].
Echocardiography, either TTE or TOE, is the mainstay of cardiac imaging for IE diagnosis, and it must be performed as soon as IE is suspected [35]. It is considered positive for IE in the presence of vegetations and/or structural complications, including abscesses, leaflet perforation, aortic pseudoaneurysm and intracardiac fistula. Echocardiography is also useful to evaluate any associated mitral or aortic valve dysfunction and the underlying left ventricular function. Generally, TTE is the first diagnostic tool in patients with suspected IE, with a high specificity (close to 100%) and modest sensitivity (about 75%) [35]. In particular, false-negatives may be found if vegetations are small or have embolized. Therefore, the absence of vegetations on TTE does not exclude IE diagnosis, although the finding of a valve with normal morphology and function greatly reduces its probability [36]. TOE sensitivity is higher than TTE in detecting both vegetations and cardiac complications; thus, in most cases, TOE follows TTE in the diagnostic workup of IE [37][38]. TOE becomes necessary when TTE is negative (or the transthoracic window is poor) but the clinical suspicion of IE is high, a valve vegetation is found with concern of intracardiac complications (e.g., new conduction delay due to paravalvular abscess), and vegetation is associated with significant valvular regurgitation to be quantified before surgery. Conventional TOE may be completed by 3D analysis, which provides a more precise estimate of the vegetation’s size with a better prediction of the embolic risk [39].