Infective Endocarditis: Echocardiographic Imaging and New Imaging Modalities

Abstract

Infective endocarditis (IE) is a rare disease with a significant impact and an increasing mortality despite earlier diagnosis and surgical intervention. It is related to several and the main etiological agents are the Gram-positive cocci. The new guidelines propose new diagnostic criteria that consider the potentiality on integrated multimodality imaging. Echocardiography (TTE) plays a key role for the diagnosis of IE and must be performed as soon as IE is suspected. It allows to identify vegetation, abscess, new dehiscence of prosthetic valve and assesses the number, size, shape, location, echogenicity and mobility of vegetations so it also useful for prediction embolic risk. Transesophageal echocardiography (TEE) is indicated when TTE is positive or non diagnostic, in case of suspected complications and when intracardiac device leads are present. We underline the increasing role of three-dimensional (3D) echocardiography in overcoming the limit of 2DTEE in selecting the maximum true diameter of irregular masses (ie, vegetation). We also underline the diagnostic value of multislice computed tomograpfy (MSCT), cerebral magnetic resonance (RMI) and nuclear imaging and also emphasize the emerging role of particular types of endocarditis specially Lead Endocarditis. The aim of this review is to provide an overview of the imaging techniques useful for the diagnosis and identification of any complications. In our opinion, the management of IE is complex, based on an “Endocarditis team “ composed by several specialist and an integrated multimodality imaging is essential for the diagnostic approach.

INTRODUCTION

Infective endocarditis (IE) is a rare disease, but its impact is significantly affecting 3–10/100,000 per year in the population. Despite trends toward earlier diagnosis and surgical intervention, the 1-year mortality from IE has not improved in over two decades. The principal risk factors are prosthetic valve replacement, hemodialysis, venous catheters, immunosuppression, intravenous (IV) drug use, and cardiac implantable electronic device (CIED).[1] The Gram-positive cocci of the Staphylococcus, Streptococcus, and Enterococcus species account for 80%–90% of IE. The new guidelines propose new diagnostic criteria that consider the potentiality on integrated multimodality imaging so according to this new definitions include: (1) the identification of paravalvular lesions by cardiac computed tomography (CT) as a major criterion; (2) in the setting of the suspected endocarditis on a prosthetic valve, abnormal activity around the site of implantation detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT (only if the prosthesis was implanted for >3 months) or radiolabeled leukocyte single-photon emission CT (SPECT)/CT as a major criterion; and (3) the identification of recent embolic events or infectious aneurysms by imaging only (silent events) as a minor criterion.[2] The aim of this review is to provide an overview of the imaging techniques useful for the diagnosis and identification of any complications.

ECHOCARDIOGRAPHY

Echocardiography is the technique of choice for the diagnosis of IE and must be performed as soon as IE is suspected. Transthoracic echocardiography (TTE) is the recommended initial modality of choice for the diagnosis. Transesophageal echocardiography (TEE) is indicated when TTE is positive or nondiagnostic in case of suspected complications and when intracardiac device leads are present. When an initial TEE is negative, but there is a high suspicion of IE, a repeat TEE is recommended.[3] For suspected native valve endocarditis, TEE has a sensitivity of 90%–100% and a specificity of 90% for the detection of vegetations; it is superior to TTE for the detection of complications and should also be considered in Staphylococcus aureus bacteremia.[1] The major echographic criteria for IE are vegetation, abscess, and new dehiscence of prosthetic valve. Echocardiography assesses the number, size, shape, location, echogenicity, and mobility of vegetations, so it is also useful for prediction embolic risk. Hence, we can consider that TTE may be of interest in this setting: (1) native left-sided valve IE with excellent echogenicity; (2) tricuspid valve IE; and (3) detection of anterior aortic abscess, especially in prosthetic valve IE. In all other cases, TEE is the gold standard, especially for the detection of vegetation and the measurement of its length, which have a major impact on the risk of embolism and the indication of early surgery, in case of prosthetic heart valve and intracardiac device.[4,5] The specificity of echocardiography depends on distinguishing a valvular vegetation from other intracardiac masses and from ultrasound artifacts. Echocardiographic findings that may be mistaken for a vegetation include:

• Papillary fibroelastoma

• Myxomatous mitral valve disease

• Nonbacterial thrombotic endocarditis

• Thrombus

• Normal valve variants such as a Lambl excrescence.

In the differential diagnosis with myxomatous mitral valve disease generally, comparison with previous studies may help to differentiate an acute process from chronic underlying valve disease. The echocardiographic differential diagnosis between thrombus and vegetation is not always possible. Thrombus is often associated with the presence of an enlarged chamber, atrial fibrillation, a stenotic mitral valve, low cardiac output state, ventricular regional asynergies, and spontaneous contrast echoes, all of which favor blood stasis and thrombus formation.

THREE-DIMENSIONAL ECHOCARDIOGRAPHY

The role of three-dimensional (3D) echocardiography is increasing. Real-time 3D-TEE (RT3D-TEE) allows the analysis of 3D volumes of cardiac structures in any possible plane. TEE could underestimate vegetation compared to RT3D-TEE.[6] The principle limitation of the 2D-TEE is in selecting the maximum true diameter of irregular masses (i.e. vegetation). This deficiency is solved by RT3D-TEE, which allows to obtain infinite planes and a volumetric reconstruction of masses. Since major diameter is currently the cutoff point to indicate surgery in patients without other surgical indications, as well as guiding the response to established medical treatment, differences between the two techniques may have therapeutic consequences. For this reason, 3D-TEE allows a better evaluation of vegetation size, morphology, and a better prediction of its embolic risk. 3D-TEE is also useful in the assessment of perivalvular extension of the infection, prosthetic valve dehiscence, and valve perforation although 3D-TEE should still be regarded as a supplement to standard echocardiography in most cases.[7,8]

NEW IMAGING TECHNIQUES

Multislice computed tomography

Multislice CT (MSCT) can be used to detect abscesses/pseudoaneurysms with a diagnostic accuracy similar to TEE and is possibly superior in the evaluation of the consequences of perivalvular extension, including the anatomy of pseudoaneurysms, abscesses, and fistulae.[6] In aortic IE, CT allows an accurate analysis of the size, anatomy, and calcification of the aortic valve, root, and ascending aorta, which may be used to inform surgical planning. In pulmonary/right-sided endocarditis, CT may reveal concomitant pulmonary disease, including abscesses and infarcts. MSCT angiography allows complete visualization of the intracranial vascular tree. Other vascular imaging (i.e., angiography) are useful in case of suspected subarachnoid and/or intraparenchymal hemorrhage and to identify mycotic aneurysm if not detected on CT. Contrast-enhanced MSCT has a high sensitivity and specificity for the diagnosis of splenic and other abscesses.[2,3,9]

Magnetic resonance imaging

Cerebral magnetic resonance imaging (MRI) allows a better lesion characterization in patients with IE and neurological symptoms, whereas its impact on IE diagnosis is marked in patients with nondefinite IE and without neurological symptoms.[2,3,9] Cerebral MRI is, in the majority of cases, abnormal in IE patients with neurological symptoms. It has a higher sensitivity than CT in the diagnosis of the culprit lesion, in particular with regard to stroke, transient ischemic attack, and encephalopathy. MRI may also detect additional cerebral lesions that are not related to clinical symptoms.

Nuclear imaging

Nuclear molecular techniques have an increasing role for patients with suspected IE and diagnostic difficulties. SPECT/CT imaging relies on the use of autologous radiolabeled leukocytes that accumulate in a time-dependent fashion in late images versus earlier images, whereas PET/CT is generally performed using a single acquisition time point after administration of 18F-FDG, which is actively incorporated in vivo by activated leukocytes, monocyte, macrophages, and CD4+ T-lymphocytes accumulating at the sites of infection. Limitations to the use of 18F-FDG PET/CT are represented by localization of septic emboli in the brain, due to the high physiological uptake of this tracer in the brain cortex, and to the fact that at this site, metastatic infections are generally, 5 mm, the spatial resolution threshold of current PET/CT scanners.[10] A number of pathological conditions can mimic the pattern of focally increased 18F-FDG uptake that is typically observed in IE, such as active thrombi, soft atherosclerotic plaques, vasculitis, primary cardiac tumors, cardiac metastasis, postsurgical inflammation, and foreign body reactions. FDG positron emission tomography/CT could be a promising role in patients with CIED infection. However, a recent study indicated that FDG PET/CT is highly accurate for the diagnosis of skin and pocket CIED infection but low for IE.[11]

ENDOCARDITIC FINDINGS

Valvular vegetations

Valvular vegetation appears as an abnormal, echogenic mass, attached to the valve leaflet with an independent motion.[5] Aortic valve vegetations generally appear as an echogenic mass attached to the ventricular side of the leaflet with independent motion and prolapsed into the outflow tract in diastole [Figure 1]. Mitral valve vegetations are typically attached to the atrial side of the leaflets with a rapid independent motion and prolapsed into the left atrium in systole [Figures 2 and 3]. Tricuspid valve endocarditis is more likely to be associated with a higher incidence of IV drug abuse, the presence of larger vegetations, and a higher incidence of pulmonary thromboembolism.[4] Tricuspid valve vegetations often appear as a large mobile mass attached to the atrial side of the leaflet with prolapse into the right atrium in systole [Figure 4].[12,13]

Figure 1.

Transesophageal echocardiography long-axis view. Mobile echogenic aortic valve vegetation attached to the ventricular side of the posterior cusp (length 9 mm, thickness 3 mm)

Figure 2.

Transthoracic echocardiography imaging. Mobile echogenic mitral valve vegetation, with an oval shape, attached to the posterior leaflet (length 12 mm, thickness 10 mm)

Figure 3.

Transesophageal echocardiography intercommissural view. Mobile echogenic mitral valve vegetation, with an oval shape, attached to the posterior leaflet (length 8 mm, thickness 6 mm)

Figure 4.

(a) Transesophageal echocardiography imaging of a small little mobile echogenic tricuspid valve vegetation attached to the septal cusp (length 7 mm, thickness 2 mm). (b) Transesophageal echocardiography imaging of a tricuspid valve endocarditis with severe regurgitation

ABSCESS AND PERIVALVULAR INVOLVEMENT

The second major echocardiographic criterion for endocarditis is the presence of a perivalvular abscess that, on ultrasound examination, may be either echolucent or echodense.[5,6,7,8,9,10,11,12] More often abscesses occur in the valve annulus adjacent to the infected leaflet tissue and with aortic valve endocarditis. Echocardiographic findings include increased echogenicity, an echolucent area in the base of the septum, or increased thickness of the posterior aortic root [Figure 5]. A mitral annular abscess appears as increased thickening and echogenicity in the posterior aspect of the mitral annulus. Tricuspid valve endocarditis may be associated with a ring abscess, again manifested as increased thickening and echogenicity in the annulus region. The diagnosis of paravalvular abscess by TTE imaging has a lower sensitivity and specificity compared with TEE imaging because of poor ultrasound tissue penetration. TEE imaging is especially important in patients with prosthetic valve endocarditis because paravalvular abscesses are common and shadowing and reverberations from the valve prosthesis compromise the examination.[2,3,4,5] In cases where a paravalvular abscess is suspected with equivocal findings on TEE, cardiac CT may serve as a useful tool in diagnosis.[6]

Figure 5.

Transesophageal echocardiography imaging. Echodense posterior aortic abscess (length 33 mm, thickness 15 mm)

In the assessment of abscess, CT demonstrates a higher sensitivity and specificity in patients with mechanical aortic valves, whereas TEE has a higher sensitivity and specificity in patients with bioprosthetic aortic valves. These might be attributable to the less obtrusive pattern of CT artifacts compared to sonographic artifacts associated with mechanical valves. Other perivalvular complications include fistulization and pseudoaneurysm. Fistula is defined by a communication between two neighboring cavities and echographically by a color Doppler communication between two adjacent cavities. Pseudoaneurysm is characterized by a perivalvular cavity communicating with the cardiovascular lumen. Echographically, it appears as a pulsatile perivalvular echo-free space with color Doppler flow inside [Figure 6]. In this setting, 3D-TEE permits a better evaluation of perivalvular complication as through multiple reconstructions allows a better definition of the anatomical relationships with the adjacent structures [Figure 7].

Figure 6.

(a and b) Transthoracic echocardiography imaging. Anterolateral aortic pseudoaneurysm. Pulsatile perivalvular echo free-space with color Doppler flow inside with a diameter of 40 mm × 18 mm

Figure 7.

Transesophageal echocardiography imaging. Huge pseudoaneurysm adjacent to the atrial wall, communicating with ventricle and with ring perforation

Perforation is a serious manifestation of destructive IE and commonly manifests as acute valve regurgitation. It can be suspected in the presence of an eccentric regurgitant jet in a noncommissural location traversing through a breach in leaflet continuity or the presence of unexplained multiple color jets [Figure 8]. In this setting, 3D-TEE is useful for the visualization of en-face anatomic views of the valve leaflets, permitting precise characterization of the shape, size, and location of valve perforations [Figure 9].[4,5,6]

Figure 8.

Transesophageal echocardiography imaging. Perforation of the anterior cusp of tricuspid valve

Figure 9.

Real-time three-dimensional transesophageal echocardiography. Very mobile posterior (P2 scallop) leaflet vegetation with an oval shape, length 18 mm, thickness 8 mm, associated with anterior leaflet perforation

PARTICULAR TYPES OF INFECTIVE ENDOCARDITIS

Prosthetic valve endocarditis

Evaluation of prosthetic valves for suspected endocarditis can be more difficult because infection often involves the area around the ring of the prosthetic valve and for reverberations and shadowing by the prosthesis. For example, in the evaluation of mitral prostheses with TTE, the LA side of the valve is “masked” by the prosthesis, so annulus paravalvular infection not always can be detected. For these reasons, TEE imaging should be strongly considered when prosthetic valve endocarditis is suspected [Figures 10 and 11].[3,5,12] In fact, this technique has a high sensitivity and specificity for the detection of prosthetic valve endocarditis, paravalvular abscess, and prosthetic mitral regurgitation. TEE is also superior for the localization of paravalvular leaks, the assessment of prosthetic leaflet mobility/malfunction, and prosthesis dehiscence [Figure 12]. Endocarditis rarely can result in prosthetic valve stenosis due to impingement of the infected mass on leaflet opening or to an infected pannus on the upstream side of the valve. In the setting of prosthetic heart valve endocarditis, the use of 3D-TEE, however, seems to provide incremental anatomic information allowing better visualization of cardiac anatomy, diagnosis of previously missed vegetations, and further assessment of periannular extensions.[14,15] 3D-TEE is superior to 2D-TEE, especially in the assessment of paravalvular leak regurgitation (PVL) that it provides improved localization and analysis of the PVL size and shape [Figures 13 and 14].[16,17]

Figure 10.

Transesophageal echocardiography imaging of a little echogenic vegetation (length 5 mm, thickness 3 mm) attached to the posterior cusp of a bioprosthetic aortic valve associated with posterior abscess

Figure 11.

Transesophageal echocardiography imaging view of two small, filamentous, mobile, echogenic vegetations (length 8 mm, thickness 3 mm) attached to the ventricular side of an aortic valve tube (Bentall surgery)

Figure 12.

Transesophageal echocardiography imaging. Posteromedial dehiscence of mechanical mitral prosthesis

Figure 13.

Three-dimensional transesophageal echocardiography of a small mitral paravalvular posteromedial leak as seen from surgical view

Figure 14.

Three-dimensional transesophageal echocardiography. Large detachment of prosthesis with an anterolateral location and rocking prosthesis

Cardiac MDCT and molecular imaging with 18F-FDG PET can also be complementary to TTE and TEE when prosthetic valve endocarditis is suspected [Figure 15a-e].

Figure 15.

Panels (a-e): 18F-fluorodeoxyglucose positron emission tomography/computed tomography for detection of complications of infective endocarditis. Transesophageal echocardiography imaging of mobile vegetation with leaflet prolapse and severe regurgitation (a and b). On 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging, there was an 18F-fluorodeoxyglucose signal from the mitral bioprosthesis (c and d, white arrow) and evidence of a splenic abscess (c and e, red arrow)[9]

Lead endocarditis

The presence of a pacing or ICD lead has been known to be associated with IE in <1% of implanted cases.[18] Is fundamental in patients with device cardiac infection longterm risk of infection can be reduced by antibiotic prophylaxis and by all strategies reducing pocket hematomas.

Recently, the WRAP-IT study showed that an adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections while in a recent work published by Bongiorni and Zucchelli is recommended a strategy taking into account the recent availability of leadless pacemakers which potentially are less susceptible to infection, and subcutaneous cardiac devices, in which occurrence of systemic infection is unlikely.[19]

In the evaluation of leads, TEE is mandatory for the diagnosis of IE considering the poor sensitivity and specificity of TTE.

Accurate diagnosis of lead infection is important because therapy typically requires removal of the pacer leads and pacemaker in addition to prolonged antibiotics. Small fibrinous strands are common on pacer leads, and small thrombi also may be seen. There are no definitive findings that distinguish an infected from noninfected pacer lead mass, so infection can be considered when blood cultures are positive. Echocardiographically pacer lead vegetations are similar to valvular vegetations, so they appear as mobile mass attached to the pacer lead with independent motion [Figures 16 and 17]. However, TEE cannot distinguish thrombus versus vegetation, and failure to visualize a lead mass does not exclude CIED infection. The use of 3D-TTE provides additional information on visualization and passage of leads through the tricuspid valve. The ability of 3D-TEE to obtain panoramic views of longer segments of pacing leads significantly facilitates the visualization of lead vegetations. Complete removal of the device is strongly recommended, even in instances where signs of infection are limited to the generator pocket site.[20] In addition, metabolic imaging with 18-FDG PET and leukocyte scintigraphy has proven to be a useful tool in those patients considered to have an intermediate probability of IE and in those patients with suspected cardiac device IE. However, in a pilot study, PET/CT had a high sensitivity of 87% and a specificity of 100% for device pocket infection but a low sensitivity of 31% and a specificity of 62% for endocarditis.[11,12,13,14,15,16,17,18,19,20]

Figure 16.

Transesophageal echocardiography imaging. Echogenic, very mobile, vegetation with a round shape attached to the catheter in the right atrium and with a diameter of 10 mm × 11 mm

Figure 17.

Transesophageal echocardiography imaging of multiple vegetations, very mobile, with an oval shape attached to the catheter

CONCLUSIONS

Echocardiography should be performed in the clinical situations in which IE is suspected, as soon as possible in order to confirm or rule out the diagnosis.

TTE remains the initial procedure of choice in patients with a low pretest likelihood of disease because of the lower cost and risk although TEE echocardiography is more sensitive for the detection of valvular vegetations. TEE is an appropriate initial test in patients at high risk of endocarditis and in situations where TTE imaging is likely to be nondiagnostic. High-risk patients include those with prosthetic valves, congenital heart disease, previous endocarditis, new heart failure, new atrioventricular block, and community-acquired staphylococcal bacteremia. Moreover, TEE often is reasonable, particularly when the aortic valve is involved to identify paravalvular abscess and is also appropriate in patients with persistent fever, recurrent bacteremia, or new atrioventricular block – all signs of paravalvular abscess formation. The expanding role of echocardiography in the management of IE has been discussed in detail in this review. Echocardiography remains a simple but invaluable diagnostic test not only for its ability to delineate cardiac valve morphology and surrounding cardiac anatomy and function but also for its crucial role in the management of IE. The use of 3D-TEE has continued to play an emerging and complementary role and in the coming years may potentially become part of standard practice. Whereas 2D-TEE effectively reveals signs of endocarditis on native and prosthetic valves, the advent of 3D-TEE enables superior preoperative anatomic delineation and evaluation for complications of IE, with consequent improvement in surgical planning. TC and nuclear imaging play also a role in the diagnosis of IE. In our opinion, the management of IE is complex, based on an “endocarditis team” composed by several specialists, and an integrated multimodality imaging is essential for the diagnostic approach.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.