Multimodality Imaging Diagnosis in Infective Endocarditis: Comparison
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Please note this is a comparison between Version 2 by Rita Xu and Version 1 by Cristiana Bustea.

Imaging is an important tool in the diagnosis and management of infective endocarditis (IE). Echocardiography is an essential examination, especially in native valve endocarditis (NVE), but its diagnostic accuracy is reduced in prosthetic valve endocarditis (PVE). The diagnostic ability is superior for transoesophageal echocardiography (TEE), but a negative test cannot exclude PVE. Both transthoracic echocardiography (TTE) and TEE can provide normal or inconclusive findings in up to 30% of cases, especially in patients with prosthetic devices.

  • infective endocarditis
  • prosthetic valve endocarditis
  • native valve endocarditis
  • cardiac implantable electronic device infection

1. Introduction

Cardiovascular disorders exert a major impact on public health and the worldwide economy owing to their considerable expenses. Published scientific investigations have definitively demonstrated a causal association between cardiovascular risk factors and both particular clinical and preclinical conditions, including heart failure, stroke, arterial stiffness, infective endocarditis, etc. [1].
Infective endocarditis (IE) is an infection of the endocardium that may affect native heart valves, implanted prosthetic valves or various cardiac devices [2]. The incidence of IE is approximately 15 cases/100,000 population with a progressive increase registered over the last years. Despite all the advances in the diagnosis and management of the disease, mortality remains high, with up to 14–22% in-hospital mortality and up to 40% 1-year mortality [3,4][3][4]. There has been an increase in the incidence of prosthetic valve endocarditis (PVE) over the last few years, accounting for 20–30% of all cases of IE [5,6,7][5][6][7]. Also, IE induces increased myocardial production of hydrogen peroxide H2O2 and the formation of thiobarbituric acid reactive substances [8], providing evidence for the presence of oxidative stress in the heart [9].
The risk of developing IE remains high among patients with a previous history of IE, patients with surgically or transcatheter implanted prosthetic valves or with prosthetic material used for valve repairs, patients with untreated or incomplete repair of cyanotic congenital heart disease, those with surgically implanted prosthetic material (valved conduits) and patients with left ventricular assist devices [6].
Early and accurate diagnosis is critical in IE and will have an important impact on the outcome. A delayed or missed diagnosis can have catastrophic consequences: heart failure, abscess formation, atrioventricular conduction abnormalities, prosthetic valve dysfunction and embolic events. The modified Duke criteria are in use and can classify patients into one of three categories: definite, possible or rejected. Imaging plays an important role in patients with IE, and elements described with different imagistic techniques are part of the diagnostic criteria [10,11,12][10][11][12]. Current data support the role of the multidisciplinary approach in IE by a specialised endocarditis team that should include cardiologists, cardiac surgeons, infectious disease specialists, microbiologists and imaging specialists for improved management and outcome in IE [6,13][6][13]. Cardiovascular imaging has become very complex with an increasing role in the diagnosis of IE. Cardiologists trained in multimodality imaging, but also radiology and nuclear medicine specialists, are currently key members in the Endocarditis Team [6].
Echocardiography remains the first-line test, but it can be normal or inconclusive in up to one-third of cases, especially in PVE or cardiac implantable electronic device infective endocarditis (CIED-IE). Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are essential techniques and can depict major imagistic criteria for diagnosis such as vegetations, abscesses, pseudoaneurysms, intracardiac fistulas, valvular perforations or aneurysms and new dehiscence of a prosthetic valve [12,14][12][14].
The modified Duke criteria have a sensitivity and specificity of approximately 80% for native-valve IE (NVE) and significantly less for prosthetic material IE. New imaging techniques are required to improve diagnosis and consequently treatment and outcome [7,15,16,17,18,19,20][7][15][16][17][18][19][20]. Imaging tools like cardiac computed tomography angiography (CTA), 18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET-CT) and radiolabelled white-blood-cell single-photon emission tomography combined with computed tomography (WBC SPECT/CT) can reveal major criteria for diagnosis [21].
These new tests will give complementary information to echocardiography and can improve diagnostic accuracy but are also able to evaluate the severity and the extent of the infection and perform a preoperative evaluation. In the absence of a definite diagnosis after TTE and TEE, multidetector CTA and nuclear imaging techniques such as 18 F FDG PET/CT or WBC SPECT/CT can reduce the rate of misdiagnosed IE. These new imagistic tools are particularly required in the setting of PVE, the paravalvular extension of infection and cardiac implantable electronic device infective endocarditis (CIED-IE). ECG gated CTA can visualise in 3D or 4D heart valves and perivalvular tissue and can accurately identify the perivalvular extension of infection, respectively, abscesses and pseudoaneurysms [22]. The evaluation of the aortic valve and root and detection of coronary artery embolic complications can be achieved with cardiac CTA, providing important information for surgical planning. In cases with prosthetic valves with or without aortic duct prosthesis, adding CTA is advised [23].
In patients with prosthetic valves, pacemakers, internal cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs), 18 F-FDG-PET/CT has demonstrated an additional diagnostic value for cardiac infection detection but also for the detection of extracardiac infectious foci in NVE and PVE [16,24][16][24]. WBC SPECT/CT is an investigation with increased specificity but with low sensitivity and many disadvantages correlated with patient preparation and comfort. The investigation is a potential approach in patients with suspected PVE with inconclusive echocardiography. In these patients, 18 F-FDG-PET/CT is recommended as first-line investigation due to its high sensitivity in detecting active infection. In situations with inconclusive results for 18 F-FDG-PET/CT, WBC SPECT/CT is recommended due to its high specificity. In CIED-IE, 18 F-FDG-PET/CT and WBC SPECT/CT can add to the diagnosis. Pocket infections can be detected with high sensitivity by FDG-PET/CT, but for lead infections, the sensitivity is reduced [25]. Multimodality imaging has an increasing role in the diagnosis of IE. A correct imaging evaluation is dependent on the informed use of the imaging tools.

2. Nuclear Imaging Techniques

2.1. 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

An important supplementary tool to be used in difficult cases of suspected IE is 18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). This method provides functional information revealing the extent of IE before structural damage appears [83,84][26][27]. In recent ESC guidelines, there is a class I B recommendation in the diagnosis of PVE and may be considered (IIb B) in CIED-related IE [6]. Limited data are available regarding FDG-PET/CT in IE. Most studies were performed on small cohorts of patients that included together NVE, PVE and CIED-IE [85,86,87][28][29][30]. The value of FDG-PET for the detection of infections was also highlighted in a few studies addressed to a specific group of patients with PVE [10,24,88][10][24][31]. The method is superior in identifying infection in different areas within the heart, especially in difficult cases like prosthetic valves where TEE can be challenging. It can diminish the number of missed abscesses at initial echocardiographic evaluation [89][32]. Different studies have revealed that in PVE, 18 F FDG PET/CT has a sensitivity between 73 and 100% and a specificity between 71 and 100%, with a positive predictive value of 67–100% and a negative predictive value of 50–100% [10,24,25,42,82,90][10][24][25][33][34][35]. Combined with the modified Duke criteria, it leads to an increased sensitivity from 52–70% to 91–97% with the maintenance of specificity [10,24][10][24]. The sensitivity of the technique improved over time due to important technical progress and the development of acquisition protocols. A contemporary meta-analysis of 26 studies on 1358 patients showed that in recent studies, the sensitivity increased for all types of IE. The research included PVE and CIED-IE and revealed a sensitivity of 72–86% and a specificity of 83–84% with FDG-PET [91][36]. Another recent meta-analysis of 13 studies that included 537 patients found that FDG PET/CT is a useful additive diagnostic test in PVE challenging cases. The sensitivity for PVE was reported at 80.5% and the specificity at 73.1% when compared to the modified Duke criteria [92][37]. A systematic review and meta-analysis with the objective to assess the value of FDG-PET/CT and radiolabelled WBC scintigraphy, for the diagnosis of CIED infection, revealed for FDG-PET/CT a pooled sensitivity of 87% (95% CI, 82–91%) and a pooled specificity of 94% (95% CI, 88–98%). Both nuclear methods yield high sensitivity, specificity and accuracy for the diagnosis of CIED infection. The scientific evidence is stronger for 18 F-FDG PET-CT and more limited for WBC scintigraphy [93][38]. In a prospective study by combining CTA with FDG PET CT, the diagnostic accuracy was improved, reaching a sensitivity of 92% and a specificity of 91%, with a positive predictive value of 93% and a negative predictive value of 88% in PVE and CIED-IE [24]. A standardised semiquantitative measure of FDG uptake increased sensitivity to 100% without reducing specificity [88][31]. FDG PET/CT reclassified 76% of patients with possible NVE and PVE/ascending aortic prosthesis infection according to modified Duke criteria into definite IE in a recent study. Extracardiac infectious foci were revealed in the same study in 28% of patients [87][30]. FDG PET/CT was also studied for its prognostic significance in a prospective study that included 179 patients with suspected IE. A significant correlation was found in patients with PVE between a positive FDG PET CT and adverse events such as unplanned heart surgery and death. Furthermore, in patients with NVE and PVE, a more intense FDG uptake is correlated with an increased incidence of embolic events [94][39]. PET/CTA findings are a major criterion in the diagnosis of IE in ESC guidelines [6]. Images registered after recent surgery need to be interpreted by taking into account the postoperative early structural and metabolic changes due to postoperative inflammation and avoiding their labelling as a positive pathological result. Previous guidelines recommend postponing PET/CTA to 3 months after surgery [10] although this 3-month period of safety is not based on much scientific evidence, and several studies have questioned it [4]. European Association of Nuclear Medicine guidelines recommend a period of only 1-month minimum interval after surgery. It seems that postoperative inflammation can be differentiated from active infection. Prostheses often present with a characteristic pattern of homogenous and diffuse mild FDG uptake in the postoperative period. This finding combined with the absence of anatomic lesions constitutes the normality pattern [88,95][31][40]. The technique and the materials used during surgery have a role in influencing the accuracy of FDG-PET/CT examination [96,97][41][42]. A surgical adhesive known as Bio Glue (Cryolife Inc., Kennesaw, GA, USA), used especially in patients with aortic root grafts with a prosthetic valve [88][31], and the Medtronic Mosaic bioprosthetic mitral valve were reported to be correlated with false-positive results [98][43]. PET/CTA can depict metabolic and anatomic findings. Anatomical lesions such as vegetations, fistulas, pseudoaneurysms, and abscesses determined by IE can be depicted by CTA. A visual analysis regarding the location and distribution of the FDG uptake, as well as a quantitative evaluation of the intensity of uptake, can be performed. An absent or a homogenous diffuse uptake of FDG is considered normal. PVE can be excluded if there is no FDG uptake. An increased ratio between FDG uptake at the level and around the prosthesis and the background standardised FDG uptake of >4.4 is suggestive of PVE [25]. In general, a focal or diffuse and heterogeneous uptake is a sign of infection and should be considered a major criterion for PVE [6]. A new index was proposed by Roque et al., the valve uptake index (VUI), that can improve the correct interpretation of patterns of distribution and will increase diagnostic ability in PVE. These characteristics are stable for a minimum of 1 year post-surgery, and there is no objective reason to postpone PET/CTA examination [99][44]. A negative PET/CTA can rule out infection, and this is an important advantage in PVE suspicion [97][42]. FDG PET/CT should be performed as early as possible in the diagnosis of IE because, after the initiation of antibiotics, the low inflammatory activity can create confounding results [88,100][31][45]. Whether prior antibiotic treatment affects the diagnostic accuracy of nuclear imaging methods remains an area of debate. In a recent retrospective study on 153 patients who underwent 171 FDG PET/CT studies, including 119 studies performed while patients were receiving antibiotic therapy, no significant impact on the diagnostic performance of FDG PET/CT studies was found [101,102][46][47]. Another study on 80 patients did not reveal any influence of prolonged antibiotic therapy before the procedure on the imaging results [85][28]. On the other hand, a few other studies have shown a possible decrease in the sensitivity of FDG PET/CT when investigating suspected CIED infection in patients already treated with antibiotics [103,104][48][49]. Prior antibiotic therapy had no significant influence on the diagnostic accuracy of labelled WBC SPECT-CT in 319 studies performed on 271 patients with suspected bacterial infections, in whom the sensitivity was 88.7% in 169 patients on antibiotic therapy and 92.1% in those who were not receiving antibiotics [105][50]. Other studies observed false-negative results in patients with suspected IE [106,107][51][52] and in patients with suspected CIED infection [108,109][53][54] who received prior treatment. FDG PET/CT has increased sensitivity but lower specificity because FDG uptake may be more intense due to inflammation of non-infectious aetiology [4,25][4][25]. In situations with false-positive results, WBC SPECT-CT or other imaging tests are preferred [4,6,106][4][6][51]. False-positive results may be recorded in recent thrombi [110][55] and inadequate patient preparation. False-negative results are produced in the case of small-size vegetations, prior antibiotic treatment and elevated blood glucose levels. FDG uptake has a characteristic pattern and distribution type that should be used as diagnostic criteria. Diagnostic accuracy is also affected by the time of scanning [4]. In a patient with suspected PVE, especially if the echocardiographic evaluation is inconsistent, the diagnostic approach will include local evaluation of the heart infection, and this will be a major diagnosis criterion but also include extracardiac assessment to evaluate the distant lesions which will constitute minor criteria. PET/CTA permits the evaluation of the distant lesions and the source of IE or can establish an alternative diagnosis if PVE is excluded [32,88][31][56]. The evaluation of distant emboli and foci of infection, with the exception of brain involvement where there is an increased physiologic FDG uptake, is another advantage of 18 F FDG PET/CT [6,10,16,19,20][6][10][16][19][20]. Cardiac physiologic uptake may be suppressed with a diet that includes high fat and low carbohydrate intake and/or a prolonged fast before the examination [111][57]. A retrospective study that focused on extracardiac findings found that 23.6% of patients had extracardiac lesions, and in many of them, this led to treatment modifications [19]. The detection rate of extracardiac infectious lesions in a meta-analysis of 13 studies was 17% and varied with the type of IE, the etiologic agent and the timing of the procedure [92][37]. The value of FDG-PET in the diagnosis of NVE is reduced, but it can detect the source of infection and the extracardiac complications of NVE [112,113][58][59]. In NVE, the role of FDG PET/CT was mostly evaluated in retrospective studies [87,114][30][60] and revealed a reduced sensitivity for diagnosis of 14% with a correct diet and even less (6%) without the diet [20,90][20][35]. FDG-PET/CT was studied in 64 patients with NVE and in 109 patients with PVE. FDG-PET/CT performed much better in PVE than in NVE, regarding the sensitivity of diagnosis (83% vs. 16%) and as a predictor of a worse outcome [94][39]. At present, in NVE, 18 F-FDG PET/CT has a limited role in cardiac infection evaluation because the sensitivity of the method is poor but can be used for the detection of a distant septic embolism, which represents a minor criterion for diagnosis [87][30]. 18 F-FDG PET/CT can be considered as an imaging method in patients with CIED-related infections [115][61]. PET/CT positive results correlated well with the clinical, microbiological and echocardiography findings of device-related infection. The reported accuracy of FDG PET/CT is variable regarding device-related infections with values of 80–89% sensitivity, 86–100% specificity, 94–100% positive predictive value and 85–88% negative predictive value [4,116,117][4][62][63]. A lower accuracy of diagnosis in CIED-IE was reported in a prospective study with a sensitivity of 31% and 63% specificity [104][49]. Lead infection was detected with a sensitivity of 24–100%, specificity of 79–100%, positive predictive value of 66–100% and 73–100% negative predictive value in different studies. Pocket infection was diagnosed with a sensitivity of 87–91%, specificity of 93–100%, 97% positive predictive value and 81% negative predictive value [104,116,118][49][62][64]. An increased specificity was also revealed in a recent study on 63 patients with suspected CIED infection. For lead infection, the sensitivity was only 38.5% but with an increased specificity of 98% [119][65]. In a meta-analysis conducted on 14 studies that included almost 500 patients, the pooled sensitivity was 83% and specificity 89%. There was a better diagnostic performance for pocket infection than for lead infection [120][66]. Another meta-analysis of 11 studies showed a sensitivity of 87% and a pooled specificity of 94% of FDG PET CT for CIED infection [93][38]. Moreover, the sensitivity and specificity were very good in pocket infection (93–96% and 97–98%, respectively), better compared to the diagnostic accuracy for lead infection and endocarditis [93,121][38][67]. The accuracy of FDG PET/CT in the diagnosis of CIED infection will be further evaluated in ENDOTEP, a large French multicentre study [122][68]. If there is clinical suspicion of device-related infection, an intense and heterogeneous 18 FDG uptake along the leads is a sign of active infection, and a focal hotspot is the best criterion for lead infection [4]. The diagnostic performance is influenced by the protocol used for scanning and patient preparation and the time interval after the implantation of the device. In the first 2 months after implantation, a mild uptake can be observed, but no uptake is registered after 6 months. Scanning 3 h after 18 FDG injection leads to an increased accuracy of diagnosis compared to the 1-hour protocol, especially for lead-related infections (sensitivity 91% and specificity 100% for the device; 61% sensitivity and 79% specificity for the leads; and 94% sensitivity and 100% specificity for the pocket) [116][62]. The infection of the pocket and the extracardiac portion of the lead is detected with almost 100% accuracy in various studies (sensitivity, specificity and accuracy for the diagnoses of pocket infection were 93%, 98% and 98%, respectively) [38,93,121][38][67][69]. 18 F FDG PET/CT has additive diagnostic value to Duke criteria, especially in CIED, being able to visualise the entire device. 18 F-FDG PET-CT has the advantage of detecting multiple sites of infection (pocket/generator, leads) and septic emboli in the same examination, with all the therapeutical consequences [104,122,123][49][68][70]. PET reclassifies 90% of Duke-possible patients with suspected device infections [124][71]. CIED IE diagnosis with FDG PET/CT with cautious interpretation of data in the first 6–8 weeks after implantation has good accuracy. WBC SPECT/CT is also useful in CIED IE but is less available. However, diagnosis is commonly confirmed by revealing vegetations on the tricuspid or less frequently on the pulmonary valve with TTE combined with TEE. Intracardiac echocardiography can add to diagnosis. Perivalvular extension is rarely observed in right-heart IE. Pulmonary CT is useful for evaluating septic embolisms, pulmonary infarcts or abscess occurrence [6,80,95][6][40][72]. The disadvantages of 18 F-FDG PET-CT are the limited value in the first 2 months after implantation as FDG uptake can be present in the absence of any infection, the high cost, limited availability, radiation, complex patient preparation and the need for trained personnel. There is an increasing number of procedures like TAVI or left ventricular assist devices (LVADs), and IE related to these devices represents a new challenge [125][73]. Modified Duke criteria and echocardiography in particular have a decreased sensitivity in TAVI IE. The acoustic shadow produced by the valve stent decreases the sensitivity of echocardiographic examination [126,127,128][74][75][76]. FDG PET/CT improves the accuracy of diagnosis in these situations. In TAVI patients with suspected IE, vegetations may be found in the stent frame or outside the valve, mainly on the mitral valve, or no vegetations are found. Multiple imaging with FDG PET/CT(A) and intracardiac echocardiography can add to the accuracy of diagnosis in patients with negative TEE [129,130][77][78]. In a small study on 16 patients with suspected TAVI IE, only half of the 10 cases with definite IE were detected with echocardiography while FDG PET CT was positive in 9 of 10 cases [129][77]. Cardiac CTA or FDG PET/CT had an important role in patients with suspected TAVI IE in a retrospective multicentre study. The diagnosis was modified in one-third of patients after adding the two diagnostic tools to the modified Duke criteria [130][78]. If TAVI itself can cause an inflammatory reaction after the implantation procedure and can cause increased FDG uptake was a question to be answered in a small study that compared FDG uptake within 1 month after TAVI in a control group (31 patients) versus 14 patients with suspected TAVI IE. In the control group, seven patients (22%) had FDG uptake. In all seven patients with definite IE and in one case with rejected IE, FDG uptake was registered. A focal pattern of the uptake with less than 25% of the valve circumference affected signified true infection. A diffuse uptake that affected more than 50% of the circumference was observed in the control group and in the rejected case [84][27]. Further studies should investigate how long an increased uptake persists after TAVI and the prognostic value of FDG PET CT in this situation. Infection of LVADs is a severe complication associated with a bad prognosis [131][79]. The site of infection is more commonly at the driveline entry point through the abdominal wall but can progress to deep tissue. Infection of the central components (pump or canula) is difficult to diagnose and is correlated with a worse outcome. Echocardiography has little role due to artefacts, and the role of CCT is limited as well. 18 FDG PET/CT and radiolabelled WBC SPECT/CT are more reliable. The diagnostic performance is higher for FDG PET/CT compared to radiolabelled WBC SPECT/CT (92% vs. 75%) and could be the first-line nuclear medicine procedure [132][80]. In 28 patients with LVADs, FDG PET/CT was indicated for suspected infection. The magnitude of infection detected by PET CT correlated with prognosis [130][78]. Another study on 57 patients found similar results with increased mortality when FDG PET/CT revealed extensive involvement of the entire LVAD and the thoracic lymph nodes [133][81]. If these findings are validated in larger studies, FDG PET CT could be included in the criteria for heart transplantation, with those with widespread infection being prioritised. FDG PET and leukocyte scintigraphy are more sensitive in detecting IE than echocardiography for CIED (pacemakers, ICDs, resynchronisation therapy devices, LVAD). The method can help in the diagnosis of IE but also provide information about the cardiac lesions, increase the sensitivity in detecting abscesses and help in the decision of surgical treatment [134][82]. Moreover, 18 F FDG-PET/CT has good spatial resolution, can identify extracardiac complications and has feasible logistic and increased comfort for patients compared to leucocyte scintigraphy which requires laborious preparation and multiple visits of patients and can miss small infectious foci [4]. 18 F FDG-PET/CT has high sensitivity in PVE and good accuracy in detecting perivalvular/periprosthetic complications [6]. Multidetector cardiac CTA and 18 F FDG-PET/CT reveal complementary data in patients with IE. While multidetector cardiac CTA reveals mainly anatomical information and can detect with high sensitivity and specificity perivalvular complications and less well vegetations, 18 F-FDG-PET/CT provides functional data and can detect extracardiac involvement. By combining these two imaging tools, an increased diagnostic accuracy is achieved [24]. Added to the standard diagnostic work-up, it can change the management strategy in 25% of cases. When a hybrid PET/CT system is available, 18 F FDG PET CT should be performed together with multidetector cardiac CTA [60][83].

2.2. Radiolabelled Leucocyte SPECT/CT Scintigraphy

Promising results were observed in several research studies regarding the utility of radiolabelled WBC SPECT/CT scintigraphy in cases with high clinical suspicion of PVE without confirmation in microbiological or echocardiographic evaluations. Current ESC guidelines made a class IIa C recommendation in patients with high suspicion of PVE when echocardiography is negative or non-diagnostic and when PET/CTA is not available [6]. While the uptake of 18 Fluorine FDG in PET/CT is related to the rate of intracellular glucose metabolism which is increased in activated inflammatory cells, the increased accumulation of neutrophils at the site of infection is the basis for the diagnostic use of scintigraphy with labelled leukocytes in IE [111,135][57][84]. Rouzet et al. compared the two nuclear medicine investigations 18 F FDG PET/CT and WBC SPECT/CT in patients with suspected PVE [25]. The study confirmed the high specificity of labelled WBC SPECT/CT. Moreover, the role of SPECT/CT was especially underlined in the first 2 months after surgery when 18 F FDG PET/CT may produce false-positive results. SPECT/CT permits evaluation of infection as localisation and extension even in the early postoperative period. Furthermore, whole-body imaging allows the diagnosis of distant embolic and metastatic infectious lesions. SPECT/CT studies have high specificity in the diagnosis of PVE, NVE and CIED-IE. Inflammation–infection characterisation with autologous radiolabelled WBC is a highly specialised method that requires highly qualified personnel and multiple and long scintigraphy acquisitions. The sensitivity is limited, affecting its negative predictive value [80][72]. A stepwise approach is recommended, with FDG-PET/CT used first because it has a high sensitivity, and if the result is not certain, then WBC-SPECT/CT should be added. Both techniques proved similar accuracy in CIED-IE [93,106,108,136,137][38][51][53][85][86]. Using an imaging technique with high specificity as leucocyte scintigraphy in a group of patients selected with a high-sensitivity imaging tool is appropriate. The advantages of both nuclear methods are the ability to evaluate extracardiac areas in a single imaging procedure and reveal extracardiac infection sites as primary infective processes or as a consequence of a septic embolism with the exception of the brain where uptake is intense due to its increased metabolism [4,11,16,138][4][11][16][87] and to detect the portal of entry [24]. The detection of metastatic infection changes treatment in 35% of patients [20].

3. Cardiac Magnetic Resonance Imaging

The role of cardiac magnetic resonance imaging (CMR) in the diagnosis of IE requires further clarification. Theoretically, CMR offers a superior 3D assessment of cardiac structures and morphology compared to echocardiography or CTA. Anatomical and functional data on valvular regurgitation, as well as myocardial involvement with oedema or inflammation of associated myopericarditis, can be revealed with CMR [4,139][4][88]. CMR can depict myocardial involvement in IE and can identify vegetations and also the paravalvular extension of infection with delayed contrast enhancement [139,140,141][88][89][90]. A limited number of research studies that studied the role of CMR in IE are available, mostly case series on a reduced number of patients. Dursun et al. aimed to study the utility of CMR for the diagnosis of IE and found that CMR can detect vegetations in patients with suspected IE and can provide valuable diagnostic and prognostic information. Perivalvular involvement was revealed with delayed contrast enhancement, but only 68% of vegetations were depicted [139][88]. Zatorska et al. studied 20 patients and observed that due to a lower spatial resolution of CMR, vegetation visualisation was limited, but they observed important advantages in detecting the perivalvular extension of infection and in evaluating valvular regurgitation and myocardial inflammation [142][91]. On the other hand, CMR has a superior ability of tissue characterisation of cardiac masses and can help in differential diagnosis. A recent study that aimed to evaluate the accuracy of CMR to identify vegetations and complications of IE versus echocardiography revealed that all vegetations observed with echocardiography were also visualised with CMR. By tissue characterisation, in some cases, alternative diagnoses were confirmed (e.g., fibroelastoma, non-bacterial thrombotic endocarditis) [143][92]. In a recent retrospective study, CMR revealed inconclusive results compared to TEE in diagnosing valvular vegetations and in the clinical management of IE, suggesting that CMR cannot be validated as a confident diagnostic tool [144][93]. Further prospective studies that will address the value of CMR versus TEE for the diagnosis and management of IE are required. Future developments in the field of this rapidly evolving diagnostic method may improve the current disadvantages of CMR concerning temporal and spatial resolution. CMR is difficult to use in PVE due to artefacts produced particularly by mechanical prostheses. The information is comparable to CTA, and it can detect paravalvular abscesses, pseudoaneurysms and prosthetic valve dehiscence, but spatial resolution and morphological definition are reduced compared to CTA. It can be recommended when CTA is contraindicated or for hemodynamic evaluation. CMR has a limited role in CIED because most devices are incompatible with MRI and diagnostic utility is diminished due to magnetic susceptibility artefacts. The 2017 ACC/AHA discourage its use for diagnosing IE, being not recommended due to a lack of superiority compared with echocardiography or CTA [134][82]. Current ESC guidelines recommend MRI for the diagnosis of neurological lesions and as a diagnostic modality of choice for spondylodiscitis and vertebral osteomyelitis [6]. Cerebral MRI is the most sensitive method to detect cerebral emboli. It may provide additional diagnostic findings and may change the timing of surgery [145][94]. AHA guidelines recommend cerebral MRI in patients with neurological symptoms and suspected IE but also in asymptomatic patients with IE prior to valve surgery to evaluate the presence of mycotic aneurysms. In patients with a high suspicion of IE, cerebral MRI can increase the accuracy of Duke criteria by adding a minor criterion [134][82].

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