Perivalvular Complication in Infective Endocarditis: An Integrated Imaging Approach in the Diagnostic Workup

Abstract

Infective endocarditis (IE) is a rare disease, but its impact is significant as it affects 3–10/100,000 per year in the population. According to the current guidelines ESC 2023, the evidence of lesions characteristic of IE is a major diagnostic criterion. Echocardiography is the first-line imaging technique to diagnose IE and to assess the structural and functional damage of cardiac structures. Transesophageal echocardiography (TEE) is recommended in patients with an inconclusive or negative TTE, in patients with high suspicion of IE, as well as in patients with a positive TTE, to document local complications. Other imaging modalities, such as cardiac computed tomography and nuclear imaging, are needed to confirm or exclude the diagnosis of IE, to characterize the extent of the cardiac lesions, and to diagnose cardiac complications. The aim of this article was to review the potential role of cardiac imaging, especially of TEE and cardiac CT in evaluating IE perivalvular complications.

INTRODUCTION

Infective endocarditis (IE) is a rare disease, but its impact is significant. It affects 3–10/100,000 per year in the population and epidemiological studies suggest that the incidence is rising. The development of IE usually requires several conditions, including the presence of predisposing risk factors, pathogens entering the bloodstream, and the competence of the host’s immune response. The portals of entry of bacteria/fungi can include (i) infections of the skin, oral cavity, gastrointestinal, or genitourinary system; (ii) direct inoculation in people who inject drugs, or by any unsafe or unprotected vascular puncture; and (iii) healthcare exposure (including invasive diagnostic or therapeutic procedures, such as transcatheter or surgical techniques. Concurrently, staphylococci, oral streptococci, and enterococci are the most frequent causative organisms. The individuals at high risk of IE in whom antibiotic prophylaxis is recommended include the following: (i) Patients with previous IE, (ii) Patients with surgically implanted prosthetic valves, with transcatheter implanted prosthetic valves, and with any material used for cardiac valve repair, (iii) Patients with congenital heart disease (CHD), and (iv) Patients with ventricular assist devices as destination therapy.[1] Antibiotic prophylaxis is not routinely recommended in in patients with simple CHD and in the presence of catheter in which may be considered on individual basis. The high inhospital mortality of patients with IE (about 20%) is mainly due to its complications. These complications are essentially of cardiac, neurological, and infectious origin. Rapid diagnosis and early antibiotic treatment are of paramount importance and allow drastic reduction of the frequency and severity of such complications. The most prevalent perivalvular complications are paravalvular abscess formation, pseudoaneurysm, fistula, and dehiscence of mechanical prosthesis. According to the current guidelines ESC 2023, the evidence of lesions characteristic of IE is a major diagnostic criterion. Echocardiography is the first-line imaging technique to diagnose IE and to assess the structural and functional damage of cardiac structures. Other imaging modalities, such as cardiac computed tomography (CT) and nuclear imaging, are needed to confirm or exclude the diagnosis of IE, to characterize the extent of the cardiac lesions, and to diagnose cardiac complications. The aim of this article was to review the potential role of cardiac imaging in evaluating IE perivalvular complications.[2,3,4]

TRANSTHORACIC ECHOCARDIOGRAPHY AND TRANSESOPHAGEAL ECHOCARDIOGRAPHY

Transthoracic echocardiography (TTE) and Trans-oesophageal echocardiogram (TOE) are the first and key imaging techniques used to diagnose IE. Although three-dimensional (3D) TOE has also been shown to be useful for the diagnosis of IE and its complications, when evaluating IE on native or prosthetic valves, TTE had low sensitivity but good specificity as compared with TOE. TOE is helpful in a wide range of clinical scenarios due to the limitations of TTE to diagnose perivalvular complications and prosthetic valve endocarditis (PVE). TOE is strongly recommended in patients with an inconclusive TTE, in patients with a negative TTE and high suspicion of IE, as well as in patients with a positive TTE, to document local complications.[5,6] The main perivalvular complications include abscess, pseudoaneurysm, new dehiscence of the prosthetic valve, and intracardiac fistula. On ultrasound examination, the abscess appears as a nonhomogeneous perivalvular thickening with high echogenicity or echo-poor appearance. More often occurs in the valve annulus adjacent to the infected leaflet tissue, in the proximal septum, and with aortic valve endocarditis. An aortic abscess appears as increased thickness of the posterior aortic root [Figure 1], while a mitral annular abscess appears as increased thickening and echogenicity in the posterior aspect of the mitral annulus. Tricuspid valve endocarditis may also be associated with a ring abscess, again manifested as increased thickening and echogenicity in the annulus region.[7,8] The diagnosis of paravalvular abscess by TTE imaging has a lower sensitivity and specificity compared with TOE imaging because of poor ultrasound tissue penetration. TOE 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 [Figure 2]. In this setting, 3D-TOE can help in the evaluation of this perivalvular complication, as through multiple reconstructions allows a better definition of the anatomical relationships with the adjacent structures [Figure 3]. In cases where a paravalvular abscess is suspected with equivocal findings on TOE, cardiac CT is strongly recommended to diagnose paravalvular or periprosthetic complications and it has a Class I level of evidence B in the 2023 ESC guidelines on IE. In possible PVE, in which the examination can be compromised by shadowing and reverberations from the valve prosthesis and the echocardiography is not conclusive, [18F] fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) (A) is strongly recommended to detect valvular lesions and confirm the diagnosis of IE. This examination of nuclear imaging has a Ib class indication according to the ESC 2023 guidelines [Figure 4].[9,10] 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 [Figures 5 and 6].[11] Commonly between aortic root or coronary sinus and cardiac chambers, it can be seen. Echographically, pseudoaneurysm is characterized by a pulsatile perivalvular echo-free space at color Doppler imaging communicating with the cardiovascular lumen [Figures 7 and 8]. In this setting, 3D-TEE can also help in the evaluation of pseudoaneurysm as through multiple reconstructions allow a better definition of the anatomical relationships with the adjacent structures [Figure 9].[12,13] Furthermore, in this case, if the echocardiography is not conclusive, a cardiac CT scan is strongly recommended always with a Ib class indication according to the ESC 2023 guidelines. Finally, in the setting of the prosthetic valve, a fearful perivalvular complication is the dehiscence of the prosthetic valve. TEE is a recommended diagnostic tool in PVE because shadowing and reverberations from the valve prosthesis compromise the examination. In this setting, 3D-TEE is becoming an increasingly echocardiographic modality since it allows to manipulate and crop of images in postprocessing;[14,15,16] it enables an analysis of deep and sheltered anatomical structures by providing additional valuable information in PVE assessment. 3D-TEE en face view is particularly useful in diagnosing mitral valve prosthesis endocarditis as it allows surgical vision of the valve in the assessment of paravalvular leak regurgitation and provides improved localization and analysis of the PVL size and shape [Figure 10].[17,18,19]

Figure 1.

Transesophageal echocardiography imaging. Echodense posterior aortic abscess

Figure 2.

Transesophageal echocardiography imaging. Posterior transcatheter aortic valve abscess

Figure 3.

Real-time three-dimensional transesophageal echocardiography imaging of cleansed aortic abscess

Figure 4.

18F-fluorodeoxyglucose positron emission tomography/computed tomography. Intense 18F-fludeoxyglucose uptake near the aortic prosthesis

Figure 5.

Transthoracic echocardiography imaging of a fistula

Figure 6.

Transesophageal echocardiography imaging. Fistula between aorta and right ventricle

Figure 7.

(a-c) Transthoracic echocardiography imaging. Anterolateral aortic pseudoaneurysm. Pulsatile perivalvular echo-free space with color Doppler flow inside

Figure 8.

Transesophageal echocardiography imaging. Pseudoaneurysm at the mitral-aortic junction

Figure 9.

Three-dimensional transesophageal echocardiography. Volumetric reconstruction of a giant aortic pseudoaneurysm

Figure 10.

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

CARDIAC COMPUTED TOMOGRAPHY

Cardiac CT has a complementary role to echocardiography in the work-up of IE and does not replace echocardiography; in fact, cardiac CT has been incorporated as major diagnostic criterion to detect cardiac lesions in the 2023 ESC guidelines. According to these, cardiac CTA is recommended in patients with possible native valve endocarditis (NVE) and PVE to detect valvular lesions and confirm the diagnosis of IE and to diagnose paravalvular or periprosthetic complications if echocardiography is inconclusive.[18] CT is also recommended in symptomatic patients with NVE and PVE to detect peripheral lesions or add minor diagnostic criteria. Perivalvular extension of IE includes abscess, pseudoaneurysm, and fistula and affects 29% of native valve IE and 55% of PVE. One should also consider cardiac CT as the preferred technique (class IB recommendation) for the evaluation of coronary arteries in patients with aortic valve IE and aortic root pathology in whom surgery is being contemplated [Figure 11]. Not only does CT reduce the risk of catheter-induced aortic injury and systemic embolization of aortic valve vegetations but these findings also assist with surgical planning.[20,21] In IE, an abscess is a perivalvular cavity with necrosis and purulent material, which, as previously described and at cardiac CT, are characterized by a low-attenuation central necrotic component with a peripheral enhancing rim; instead early abscess formation can appear as soft-tissue thickening [Figures 12-14]. A pseudoaneurysm appears as a pulsatile perivalvular space with evidence of flow and direct communication with the cardiovascular lumen at color Doppler imaging. At CT, a pseudoaneurysm appears as a perivalvular contrast material-filled cavity, usually with a visible direct connection with the aortic root or cardiac chambers [Figure 15]. The sensitivity of TEE for the detection of an abscess ranges from 80% to 90% while CT had a sensitivity of 91% for the detection of abscess or pseudoaneurysm. It is reasonable to consider CT for the evaluation of perivalvular extension given that electrocardiogram (ECG)-gated CT angiography has a diagnostic value similar to that of TEE for the overall evaluation of IE and an accuracy that is equal or superior to that of TEE.[22,23] Fluorine 18 FDG PET/CT may also play a role in the assessment of PVE because abnormal FDG uptake around the prosthetic valve [Figure 16] has been found to increase the sensitivity of the modified Duke criteria at admission from 70% to 97%. A fistula is a communication between two neighboring cavities through an abnormal perforating tract and on color Doppler imaging, it appears as a tract communicating between two neighboring cavities. At CT, a fistula appears as a contrast agent-filled tract interconnecting two neighboring cavities. TEE is more effective than CT in accurately depicting intracardiac fistula. Therefore, the detection of perivalvular abscess formation and aorto-cardiac fistulas may aid in directing the timing and feasibility of surgical intervention. As previously mentioned, another perivalvular complication in the context of PVE is prosthesis dehiscence. Destruction of the valve ring leads to valve dehiscence and perivalvular leak. Dehiscence appears with paravalvular regurgitant flow at color Doppler imaging with or without rocking motion of the prosthesis. At CT, it appears as a malalignment with a tissue defect between the annulus and prosthesis [Figure 17]. Is reported in many studies a higher sensitivity for TEE than for CT in depicting paravalvular leakage, although the difference was not statistically significant, while another study showed that, compared with TEE, the preoperative single phase has similar specificity and lower sensitivity for detecting dehiscence.[24,25]

Figure 11.

Cardiac TC. Evaluation of coronary arteries disease

Figure 12.

Two-dimensional multiplanar reconstruction: Paravalvular abscess extended from 9 to 6 in clockwise with an extensive vegetation in the anterior portion (white arrow)

Figure 14.

Two-dimensional multiplanar reconstructions in late acquisition phase from a dual source-dual energy computed tomography acquisition: para-aortic abscess (white arrow) characterized by thick peripheral wal

Figure 15.

(a) Pseudoaneurysm three-dimensional volume rendering reconstruction, (b) two-dimensional (2D) multiplanar reconstruction: pseudoaneurysm extended from 6 to 11 in clockwise, (c) 2D multiplanar reconstruction: pseudoaneurysm in the subvalvular plane in direct connection to left ventricle outflow tract, fullfilled by contrast and no evidence of fistulization to the right ventricle

Figure 16.

Positron emission tomography/computed tomography image. Intense 18F-Fludeoxyglucose uptake around the aortic prosthesis

Figure 17.

Two-dimensional multiplanar reconstruction: pseudoaneurysm is associated to mechanic valve detachment, in the site of right coronary ostium

Figure 13.

Two-dimensional multiplanar reconstructions in arterial acquisition phase: extensive inflammatory fluid collection in the atrial-aortic space suggestive of para-aortic abscess (white arrow)

DISCUSSION

Current guidelines recommend that IE care should be coordinated within regions by a dedicated team that resides at a specialist center.[6] This “Infective Endocarditis” team should be comprised infectious disease specialists, cardiologists with a specialist interest in heart valve disease/cardiac imaging, cardiac surgeons, and cardiac device specialists. Transthoracic echocardiography (TTE) and Trans-oesophageal echocardiogram (TOE) are the first and key imaging techniques used to diagnose IE. When evaluating IE on native or prosthetic valves, TTE had low sensitivity but good specificity as compared with TOE. TOE is helpful in a wide range of clinical scenarios, due to the limitations of TTE to diagnose perivalvular complications, small vegetations, PVE, and vegetations associated with cardiac implantable electronic devices (CIED). TOE is strongly recommended in patients with an inconclusive TTE, in patients with a negative TTE and a high suspicion of IE, as well as in patients with a positive TTE to document local complications. Echocardiographic imaging should be performed as soon as the IE diagnosis is suspected. The degree of valvular damage, the rate of peripheral embolic events, and the need for valve surgery increase with increasing time to initial echocardiographic assessment. Echocardiography should be repeated 5–7 days after an initial normal or inconclusive echocardiography, if the suspicion of IE remains high, and in patients with diagnosed IE at high risk of complications. Cardiac CT is more accurate than TOE for diagnosing perivalvular and periprosthetic complications of IE (abscesses, pseudoaneurysms, fistulae, and prosthetic dehiscence) and is recommended in both NVE and PVE if TOE is not conclusive or not feasible. In addition, cardiac CT can significantly influence subsequent surgical decision-making. One should also consider cardiac CT as the preferred technique (class IB recommendation) for the evaluation of coronary arteries in patients with aortic valve IE and aortic root pathology in whom surgery is being contemplated. Not only does CT reduce the risk of catheter-induced aortic injury and systemic embolization of aortic valve vegetations, but these findings also assist with surgical planning. Knowledge of coronary anatomy, the presence of co-existent atherosclerotic coronary disease and proximity of coronary arteries to mycotic aneurysms and abscesses is critical to the surgical technique. The added information derived from CT pertaining to the morphology, size, and calcification of the aortic valve, aortic root, and ascending aorta is also important. The presence of a “porcelain aorta” may preclude surgery for aortic valve IE altogether. Similarly, heavy mitral annular calcification may exclude a surgical option for mitral valve IE due to a prohibitive operative risk. Despite the advantages that cardiac CT offers in patients with suspected or confirmed IE, there are qualifications, challenges, and limitations to its routine application which must be considered. Careful imaging needs to be performed to ensure optimal image quality. This includes ECG gating of images and ensuring appropriate scan protocols are selected with the appropriate exposure settings and contrast regimes.

CONCLUSIONS

Current guidelines recommend that IE care should be coordinated within regions by a dedicated team in highly specialized hospitals. This “Infective Endocarditis” team should be comprised infectious disease specialists, cardiologists with a specialist interest in heart valve disease/cardiac imaging, cardiac surgeons, and cardiac device specialists. The current guidelines emphasize the role of multimodality imaging in the diagnosis of IE. The major diagnostic criterion is the determination of a typical cardiac lesion with various imaging methods. Transthoracic echocardiography and transesophageal echocardiography remain the first and key imaging techniques used to diagnose IE. When TOE is not readily available or is contraindicated/inconclusive, the use of a cardio CT scan is essential to detect perivalvular and periprosthetic complications. Hence, we propose the role for cardiac CT in routine clinical use for suspected IE and we support the use of CT in all cases of suspected or confirmed NVE/PVE to detect paravalvular and systemic complications and in patients being planned for surgical intervention [Figure 18].

Figure 18.

Flow chart in infective endocarditis diagnosis. NVE: Native valve endocarditis, PVE: Prosthetic valve endocarditis, CT: Computed tomography, FDG-PET/CT: Fludeoxyglucose-positron emission tomography/computed tomography, MRI: Magnetic resonance imaging

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.