Summary
Infective endocarditis is a serious disease that needs rapid diagnosis and accurate risk stratification to offer the best therapeutic strategy. Echocardiography plays a key role in the management of the disease but may be limited in some clinical situations. Moreover, this method is insensitive for very early detection of the infection and assessment of therapeutic response because it does not provide imaging at the molecular and cellular levels. Recently, several novel morphological, molecular and hybrid imaging modalities have been investigated in infective endocarditis and offer new perspectives for better management of the disease.
Résumé
L’endocardite infectieuse est une maladie grave qui nécessite un diagnostic rapide et une stratification du risque précise afin définir la meilleure stratégie thérapeutique. L’échocardiographie joue un rôle clé dans la prise en charge de la maladie mais peut présenter des limites dans certaines situations cliniques. De plus, cette méthode est peu sensible pour la détection très précoce de l’infection ainsi que pour l’évaluation de la réponse thérapeutique car elle ne propose pas une imagerie au niveau cellulaire et moléculaire. Récemment, plusieurs nouvelles modalités d’imagerie morphologique, moléculaire et hybride ont été étudiées dans le domaine de l’endocardite infectieuse et offrent de nouvelles perspectives pour une meilleure prise en charge de la maladie.
Infective endocarditis: from pathophysiology to imaging
Infective endocarditis (IE) is a serious disease associated with poor prognosis despite improvements in medical and surgical therapies . IE results in a complex pathogenesis that involves many host-pathogen interactions . Indeed, previous endocardial lesions can lead to the exposure of the underlying extracellular matrix proteins, local inflammation and then thrombus formation, which is termed ‘non-bacterial vegetation’. In the case of bacteraemia, valves with pre-existing sterile vegetations or tissues with minimal lesions can be colonized because of strong interactions between the bacteria, platelets and endothelial cells via several bacterial surface proteins or plasma-bridging molecules. This process leads to the recruitment of circulating inflammatory cells and the release of cytokines and procoagulant factors, which contribute to the enlargement of vegetations and the protection of bacterial pathogens from host defences. Ultimately, valvular and perivalvular tissues are destroyed, thus increasing the risk of valve dysfunction, abscess formation and embolization . Moreover, in addition to embolic events, other extracardiac life-threatening complications may occur, such as infectious aneurysms and intracranial and visceral haemorrhages.
Therefore, early and reliable diagnostic and risk stratification strategies are critical to reduce delays to the start of appropriate antimicrobial therapy and to identify patients who require urgent valve surgery. As described in recent international recommendations, echocardiography is a simple accurate method for detecting endocardial damage in IE and helping in risk stratification . However, echocardiography studies may be limited in some clinical situations and this technique is insensitive for very early detection of infection because it does not provide an imaging assessment of IE at the molecular and cellular levels. Recently, other morphological and molecular imaging strategies have emerged for the detection of endocardial involvement and extracardiac complications.
The aims of this review are to provide an update on the value of echocardiography in the management of IE, to discuss the potential role of other imaging techniques and, finally, to consider the challenges and perspectives in the imaging investigations.
Morphological imaging of endocardial damage and its consequences
Echocardiography: the main imaging modality
Echocardiography plays a key role not only in the diagnosis of IE but also in the prognostic assessment and follow-up under therapy and during surgery. Recently, recommendations for the practice of echocardiography in IE have been published, to provide an update on the value and limitations of this technique in IE and to define the optimal use of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TEE) .
Echocardiography for the diagnosis of infective endocarditis
Although IE may present with several very different initial symptoms, its diagnosis usually relies on the association of clinical, microbiological and morphological criteria, which are included in the modified Duke classification . By detecting several forms of endocardial damage, echocardiography remains an accurate method for providing the major diagnostic criteria of IE. Knowledge of the anatomical features of IE is fundamental in order to better understand, analyse and describe the echocardiographic findings ( Table 1 ). TTE is the initial technique of choice for investigation. A normal scan in low-risk patients provides rapid non-invasive confirmation that the diagnosis is unlikely. Moreover, TTE is better than TEE for the detection of anterior cardiac abscesses and for haemodynamic assessment of valvular dysfunction. Because of its higher sensitivity and specificity, TEE is recommended in cases of: negative TTE associated with high clinical suspicion; poor TTE quality; presence of prosthetic valves or intracardiac device; and positive TTE ( Fig. 1 ). In preliminary studies, three-dimensional TEE provided incremental value over two-dimensional TEE in its ability to accurately identify and localize vegetations and to identify complications such as abscesses, perforations and ruptured chordae ( Fig. 2 ). Thus, echocardiography must be done rapidly and repeated once a week as soon as it is negative but the condition is suspected.
| Surgery/necropsy | Echocardiography | |
|---|---|---|
| Vegetation | Infected mass attached to an endocardial structure or on implanted intracardiac material | Oscillating or non-oscillating intracardiac mass on valve or other endocardial structures, or on implanted intracardiac material |
| Abscess | Perivalvular cavity with necrosis and purulent material not communicating with the cardiovascular lumen | Thickened, non-homogeneous perivalvular area with echodense or echolucent appearance |
| Pseudoaneurysm | Perivalvular cavity communicating with the cardiovascular lumen | Pulsatile perivalvular echo-free space, with colour Doppler flow detected |
| Perforation | Interruption of endocardial tissue continuity | Interruption of endocardial tissue continuity traversed by colour Doppler flow |
| Fistula | Communication between two neighbouring cavities through a perforation | Colour Doppler communication between two neighbouring cavities through a perforation |
| Valve aneurysm | Saccular outpouching of valvular tissue | Saccular bulging of valvular tissue |
| Dehiscence of a prosthetic valve | Dehiscence of the prosthesis | Paravalvular regurgitation identified by TTE/TEE, with or without rocking motion of the prosthesis |
Echocardiography for risk stratification and follow-up of infective endocarditis
In addition to its role in diagnosing IE, echocardiography also has major prognostic value in IE in predicting death and complications . Heart failure, perivalvular extension and embolic events represent the three most frequent and severe complications of IE. Echocardiography plays a key role in the management of these complications by helping a decision to be made regarding valve surgery and its optimal timing.
Heart failure represents the main indication for valve surgery in IE and the operation is usually indicated in an emerging (within 24 hours) or urgent (within a few days) setting . TEE allows identification of the mechanisms responsible for these complications, such as acute valve regurgitation, valve obstruction or intracardiac fistula. Moreover, TTE may provide criteria of poor haemodynamic tolerance, such as torrential regurgitation, elevated left and right filling pressures, pulmonary arterial pressures and ventricular dysfunction. Even in the absence of clinical congestive signs, the presence of these echocardiographic signs suggests the need for valve surgery because the evolution to heart failure usually is inevitable .
Perivalvular extensions are present in around 20% of cases and indicate valve surgery because they expose the patient to risks of: heart failure by the occurrence of fistula or prosthetic valve dehiscence; complete atrioventricular block by interruption of the cardiac conduction system; and persistence of the infection . TEE is the technique of choice for the diagnosis of perivalvular extension and its resulting complications but TTE seems better in case of anterior abscess of the aortic annulus .
Embolic events are frequent and life-threatening complications of IE, which are symptomatic in around 20–25% of cases and silent (only detected by cerebral imaging) in almost 50% of cases . These events are factors for poor prognosis, especially in case of involvement of the cerebral circulation bed . Echocardiography, especially TEE, is useful for the evaluation of embolic risk at admission, by providing the maximal length, mobility and location of vegetations. Indeed, large and highly mobile vegetations are associated with a higher risk of embolism , especially in the mitral position . This evaluation must be performed very early in the course of IE because the risk of embolic events remains high during the first week after diagnosis and initiation of antibiotics . Therefore, valve surgery should be performed in an urgent setting when a large vegetation (> 10 mm) is present following one or more embolic episodes. In addition, when associated with other known predictors of a complicated course (heart failure, persistent infection under therapy, abscess and prosthetic endocarditis), the presence of a large vegetation (> 10 mm) indicates an earlier surgical decision. Finally, the decision to operate in the case of an isolated very large vegetation (> 15 mm) is more difficult and must be specific for the individual patient. Surgery may be preferred when a valve repair seems possible, particularly in mitral valve IE . Nevertheless, the prediction of embolism remains challenging and should take into account other criteria, such as the type of microorganisms ( Staphylococcus aureus ) and conditions associated with a prothrombogenic state (atrial fibrillation, diabetes, etc.). Recently, a randomized trial demonstrated that early surgery in patients with large vegetations and significant valve dysfunction significantly reduced the composite endpoint of death from any cause and embolic events by effectively decreasing the risk of systemic embolism compared with conventional therapy . Although this result is of crucial importance, it was limited by the fact that it was obtained in a population with a very low operative risk. Thus, we now have strong evidence that early surgery reduces embolic risk but we need better risk stratification in order to evaluate accurately the benefit-risk ratio of this procedure. Indeed, for a high embolic risk associated with a low or intermediate predicted operative mortality (computed by scoring systems), the benefit of early surgery would be greater.
Intraoperative TEE is mandatory in patients operated on for IE; it provides the surgeon with a final anatomical evaluation of valvular and perivalvular damage, and is particularly useful for assessing the immediate result of conservative surgery, as well as in cases of complex perivalvular repair . Finally, echocardiography must be used for follow-up of patients with IE under antibiotic therapy and after surgery, along with clinical follow-up. The number, type and timing of repeat examinations depend on clinical presentation, type of microorganism and initial echocardiographic findings. After hospital discharge, the main complications include recurrence of infection, heart failure, need for valve surgery and death. Thus, clinical and echocardiographic periodic close follow-up (at 1, 3, 6 and 12 months) is mandatory during the first year after the end of antibiotic treatment .
Limitations of echocardiography in infective endocarditis
A negative echocardiogram may be observed in about 15% of cases of IE. The imaging diagnosis may be particularly challenging in some cases, such as with intracardiac devices, valvular prostheses, the presence of pre-existing severe lesions (mitral valve prolapse, degenerative lesions), very small vegetations and abscesses or no vegetation. In addition, the diagnosis may be difficult at the early stage of the disease. Conversely, false diagnosis of IE may occur in other situations: for example, it may be difficult to differentiate between vegetations and thrombi, cusp prolapse, cardiac tumours, myxomatous changes, Lambl’s excrescences or strands. Thus, in some situations, the echocardiogram remains negative or doubtful, even if it is performed by expert hands and after a repeat examination . Innovations in the specialty of diagnostic strategy have emerged to resolve these issues through new imaging modalities. Multislice computed tomography (CT) and magnetic resonance imaging (MRI) might help to better identify both anatomical intracardiac damages and extracardiac complications. Positron emission tomography (PET) and other molecular imaging methods might provide imaging of the inflammation and infection at molecular level and will be fused with ‘anatomical’ imaging.
Multislice computed tomography
Recent advances in the temporal and spatial resolution of multislice CT scanners allow high-resolution cardiac imaging. Currently, the major application of multislice CT is in the evaluation of coronary artery disease but it has been used also for heart valve disease, such as aortic stenosis and, more recently, in IE .
In a small study of 37 consecutive patients with clinically suspected IE, Feuchtner et al. found good results in detecting IE valvular and perivalvular damage using electrocardiogram (ECG)-gated 64-slice CT or dual-source CT. The diagnostic performance of CT for the detection of evident abnormalities for IE compared with TEE was: sensitivity 97%, specificity 88%, positive predictive value (PPV) 97% and negative predictive value (NPV) 88% on a per-patient basis. In a per valve-based analysis, the diagnostic accuracy for the detection of vegetations and abscesses/pseudoaneurysms compared with surgery was: sensitivity 96%, specificity 97%, PPV 96%, NPV 97% and sensitivity 100%, specificity 100%, PPV 100%, NPV 100%, respectively, without significant differences compared with TEE. Although the small leaflet perforations were missed, CT provided more accurate anatomical information regarding the perivalvular extent of abscesses/pseudoaneurysms than TEE . Gahide et al. found similar results in patients with aortic valve IE .
As prosthetic valve IE represents one of the most difficult situations for echocardiographic studies, Fagman et al. recently investigated the role of ECG-gated 64-slice CT in the diagnosis of aortic prosthetic valve IE. In 27 patients, the authors showed that the strength of agreement between ECG-gated CT and TEE was good for abscess and dehiscence, and moderate for vegetation. In comparison with intraoperative findings, CT detected three additional pseudoaneurysms that were unnoticed by TEE. In two of these cases, the pseudoaneurysm was located close to the right coronary cusp, a location that is difficult to investigate by TEE .
Thus, this imaging modality offers the possibility to rapidly image the heart and other organs and thus to identify both cardiac lesions and extracardiac complications, such as embolic events, infectious aneurysms, haemorrhages and septic metastases, which can modify the therapeutic strategy ( Fig. 3 ). Moreover, it provides an anatomical assessment of the coronary bed, which is important in the preoperative evaluation . CT seems to be especially useful in case of a negative or inconclusive echocardiographic study. However, contrast products should be used with caution in patients with renal failure or haemodynamic instability because of the risk of worsening renal impairment in combination with antibiotic nephrotoxicity. In some cases, the indications for a CT scan might be limited to the brain and its arteries. Specific recommendations are needed to clearly define the appropriate situations where this modality should be used.
