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Echocardiography in Infective Endocarditis
Introduction
Infective endocarditis (IE) is a serious infection of the heart that, despite advances in diagnosis and treatment, is associated with in-hospital and 1-year mortalities of approximately 20% and 40%, respectively. IE is also associated with major morbidity with embolic events (stroke in 17% of patients, non-neurologic embolus in 23%), heart failure (32%), abscess (14%), and the need for surgery (48%) being relatively common events. With an overall incidence of 3–10 per 100,000 patient years, in the United States alone there are over 50,000 cases per year, the majority of which affect the left side of the heart. Risk factors for endocarditis include the presence of a valve prosthesis or other implanted device, intravenous drug abuse, diabetes, and immunosuppression.
Echocardiography is integral to the diagnosis and management of this condition because it can identify vegetations and complications associated with spreading infection, assess the severity of concomitant valve dysfunction, and document the impact of the disease on ventricular function and cardiovascular hemodynamics including pulmonary artery pressure. This chapter focuses on the role of echocardiography in IE with an emphasis on native and prosthetic valves. It discusses the imaging features of vegetations and complications of endocarditis including embolus, abscess, perforation, and other forms of valvular disruption, and in the case of prosthetic valves, variable degrees of dehiscence. It also covers the prognostic role of echocardiography, particularly in the prediction of embolic risk, and emphasize the important role that echocardiography plays during follow-up of treatment, and for intraprocedural guidance during surgical intervention. Where specific recommendations for the use of echocardiography are provided, they are consistent with the current American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Management of Patients with Valvular Heart Disease, (with the 2017 update including no changes related to echocardiography) European Society of Cardiology (ESC) Guidelines for the Management of Infective Endocarditis, ESC Recommendations for the Practice of Echocardiography in Infective Endocarditis, the AHA Scientific Statement on Infective Endocarditis, and ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography.
Although a full discussion of the etiology, pathophysiology, natural history, and optimal approaches to management such as surgical decision making is beyond the scope of this chapter, the reader is referred to the ACC/AHA and ESC Guidelines and AHA Scientific Statement for this information. It is worth noting that echocardiography has served as a research tool in many of the studies that form the basis for these documents. Additionally, the echocardiographic assessment of the hemodynamic severity of valve lesions caused by IE and associated changes in cardiac function are critical to clinical decision making in IE, and the reader is referred to Chapter 8, Chapter 9, Chapter 10, Chapter 28, Chapter 29, Chapter 30, Chapter 31 for a more detailed discussion of the tools that are used to make these assessments.
Diagnosis
Indications for Transthoracic Echocardiography and Transesophageal Echocardiography
Echocardiography is essential for the diagnosis of IE ( Table 40.1 ). Endocarditis may be suspected in a wide variety of situations, most commonly with otherwise unexplained fever lasting at least 48 hours, bacteremia, a new regurgitant heart murmur, new conduction disturbance, and/or embolic events. Although 90% of cases of IE are associated with bacteremia, 10% have culture-negative endocarditis, which may reflect the presence of difficult-to-culture organisms such as the HACEK ( Haemophilus , Aggregatibacter , Cardiobacterium hominis, Eikenella corrodens , and Kingella ) species or the institution of antibiotic therapy before blood cultures are drawn. Although the clinical presentation is most typically subacute, valvular disruption and associated sudden severe valvular regurgitation may be associated with acute heart failure or shock.
TABLE 40.1
Role of Echocardiography in Infective Endocarditis
Data from Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2014;63(22):2438-2488; Habib G, Badano L, Tribouilloy C, et al. Recommendations for the practice of echocardiography in infective endocarditis. Eur J Echocardiogr . 2010;11(2):202-219; and Douglas PS, Garcia MJ, Haines DE, et al. 2011 appropriate use criteria for echocardiography. J Am Coll Cardiol . 2011;57(9):1126-1166.
| 2014 ACC/AHA Guidelines | 2015 ESC Guidelines | 2011 ASE Appropriate Use Criteria | ||||||
|---|---|---|---|---|---|---|---|---|
| Should Be Performed (Class I) | Reasonable to Perform (Class IIa) | May Be Considered (Class IIb) | Recommended/Indicated (Class I) | Should Be Considered (Class IIa) | May Be Considered (Class IIb) | Appropriate | Rarely Appropriate | |
| TTE |
|
|
|
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| TEE |
|
|
|
|
|
|
|
|
| TTE and/or TEE |
|
|
|
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| Intraoperative TEE |
|
|
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| Intracardiac echo |
|
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ACC , American College of Cardiology; AHA , American Heart Association; ESC , European Society of Cardiology; HF , heart failure; IE , infective endocarditis; LOE , level of evidence; TEE , transesophageal echocardiogram; TTE , transthoracic echocardiogram.
The diagnosis of endocarditis is typically based on the Modified Duke criteria ( Tables 40.2 and 40.3 ). In these criteria, echocardiographic evidence of endocarditis, as defined by the presence of vegetation, abscess, or new dehiscence of a prosthetic valve, is one of the major criteria; new valvular regurgitation, which can also be identified by echocardiography, is a second major criterion.
TABLE 40.2
Modified Duke Criteria for Diagnosis of Infective Endocarditis
Adapted from Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis . 2000;30(4):633-638.
| Definite IE | Possible IE | Rejected IE |
|---|---|---|
| Presence of ANY of the following: Pathologic criteria
Clinical criteria b
|
|
IE , Infective endocarditis.
a Modification from the original Duke criteria.
b See Table 40.3 for definitions of major and minor criteria.
TABLE 40.3
Definition of Terms Used in the Modified Duke Criteria for Diagnosis of Infective Endocarditis
Adapted from Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis . 2000;30(4):633-638.
| Major Criteria | Minor Criteria |
|---|---|
Blood culture positive for IE
|
Predisposition, predisposing heart condition, or injection drug use |
| Evidence of endocardial involvement | Fever, temperature >38°C (100.4°F) |
Echocardiogram positive for IE, defined as follows:
Note: TEE is recommended in patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE (paravalvular abscess); TTE is first test in other patients. a |
Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions |
| New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient) | Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor |
| Microbiological evidence: positive blood cultures that do not meet major criteria; or serologic evidence of active infection with organism consistent with IE | |
| Echocardiographic minor criteria eliminated a |
HACEK , Haemophilus , Aggregatibacter , Cardiobacterium hominis, Eikenella corrodens , and Kingella ; IE , infective endocarditis; TEE , transesophageal echocardiogram; TTE , transthoracic echocardiogram.
New valvular regurgitation may be on the basis of cusp/leaflet perforation, chordal rupture, or altered cusp/leaflet coaptation caused by bulky vegetations. Valve stenosis is a less common complication but may occur with prosthetic valve IE in which a bulky vegetation obstructs the orifice or a strategically placed smaller vegetation impedes mechanical disk motion. Note that it may be difficult to distinguish superimposed vegetation when there is a flail segment due to chordal rupture. Although transthoracic echocardiography (TTE) is typically the initial study (Class I in ACC/AHA and ESC Guidelines; see Table 40.1 ), there should be a low threshold for transesophageal echocardiography (TEE). Indeed, as listed in Table 40.1 , there are number of scenarios for which TEE has Class I, IIA, and IIB indications for diagnosis. The IIB indication (TEE may be considered) for nosocomial Staphylococcus aureus bacteremia with a portal of entry from a known extracardiac source exists because IE has been reported to occur in approximately 30% of patients with S. aureus bacteremia particularly in patients with osteomyelitis, prolonged bacteremia, or hemodialysis catheters. The European recommendations (see Table 40.1 ) offer expanded recommendations for TEE including its use in patients with a high clinical suspicion of infectious endocarditis but a normal TTE and suggest that TEE should be considered in the majority of adult patients with suspected IE even when the TTE is positive. TEE should not be performed in patients with a negative TTE of excellent quality when there is a low clinical suspicion of IE.
TTE has a reported sensitivity of 62%–82% and a specificity of 91%–100% for native valve endocarditis and is most likely to detect vegetations larger than 3 mm in size. For prosthetic valve endocarditis, the sensitivity is only 36%–69%. TEE with spatial resolution of 1–2 mm has a reported sensitivity of 87%–100% and specificity of 91%–100% for native valve endocarditis. Notably, although the sensitivity of TEE for prosthetic valve endocarditis is significantly higher than that of TTE, it is still somewhat lower than that for native valve endocarditis, but can increase with follow-up studies when the initial study is negative but the clinical suspicion of IE is high. TEE has a specificity of over 90% for prosthetic valve endocarditis.
As discussed later, there are a number of reasons for which echocardiography, even TEE, may be negative in cases of IE. Therefore, if the clinical suspicion of endocarditis remains high, it is reasonable to repeat echocardiography, typically after 7–10 days. A similar approach is reasonable in cases of suspected abscess, but a shorter interval between initial and subsequent echoes is probably warranted because there can be dramatic changes in the appearance of an abscess over the course of even several hours. Additional indications for repeat echocardiographic evaluation include a clinical change in a patient with established endocarditis and surveillance without clinical change in patients at high risk for complications based on the extent of infection or organism ( Staphylococcus , Enterococcus or fungus [AHA/ACC Class I]). Conversely, there is no indication for TEE or follow-up TTE when the initial transthoracic echo is of high quality and there is a low clinical suspicion of endocarditis.
Vegetations
Vegetations are identified by the presence of echogenic masses of variable size that typically have oscillating motion independent of the surface to which they are attached ( Fig. 40.1 and 
, ). Their echotexture is typically similar to that of the myocardium although they can become more echodense during the course of treatment ( Fig. 40.2 and 
). They have irregular shapes and may prolapse from one chamber to the other during the cardiac cycle. By far the most common location for vegetations is on the cardiac valves, either native or prosthetic, but they may also be encountered on indwelling foreign bodies such as pacer/automated implantable cardioverter defibrillator (AICD) leads and central lines. Rarely, vegetations are encountered on the endocardial surface of the ventricles or aorta at sites impacted by jet lesions (for example, on the right ventricular side of a restrictive ventricular septal defect [VSD]).
Vegetations are typically seen on the low-pressure aspect of valves or shunts ( Fig. 40.3 ) and usually at the site of endothelial damage, which may be the result of preexisting structural disease. With endothelial damage, blood-borne organisms can adhere to associated platelet and fibrin aggregates. Thus, vegetations are more common on the ventricular surface of the aortic valve, particularly in the presence of aortic regurgitation, and on the atrial surface of the mitral and tricuspid valves, particularly in the presence of mitral or tricuspid regurgitation. Pulmonic valve endocarditis is a very rare entity but in the absence of data, it would be predicted that pulmonic endocarditis would have a predilection for the right ventricular aspect of the valve. The presence of a mass that might be confused with vegetation on the high-pressure aspect of the valve favors an etiology other than vegetation. However, these rules are by no means definitive, and it should be noted that the ventricular surface of the anterior mitral leaflet may be infected when in the path of an aortic regurgitant jet and chordal involvement of both the mitral and tricuspid valves may also occur.
Although the echotexture of vegetations is frequently homogeneous, inhomogeneity with areas of echolucency may also occur, particularly if vegetations are very large ( Fig. 40.4 ). When IE is suspected, nonstandard views are essential, and when involvement of the mitral and tricuspid valves is suspected, it is imperative to get multiple views so that each of the scallops and leaflets is visualized (see Chapter 28, Chapter 30 for a description of the views needed to image all six mitral scallops and three tricuspid leaflets). With prosthetic valves, particularly mechanical prostheses, vegetations may be smaller and more difficult to detect because of shadowing from prosthetic elements. Additionally, mechanical prosthetic valves are more likely to have early perivalvular spread with abscess, pseudoaneurysms, and dehiscence, than bioprostheses in which infection is more likely to involve the cusps.
Echocardiography should address the number, size, shape, location, mobility, and echogenicity of vegetations, because many of these features have prognostic value as discussed later. Although not widely used, a scoring system has been proposed with mobility broken down by grade, with grade 1 being fixed, grade 2 a fixed base but a free edge, grade 3 pedunculated, and grade 4 prolapsing. Increased echogenicity suggests a degree of organization or chronicity (see Fig. 40.2 and ).
Reasons for which echocardiography, even TEE, may be unable to detect vegetations, include situations in which vegetations are very small, atypically located, sessile, or obscured by calcification. Thus, repeat echocardiography is warranted in cases where the clinical suspicion is high.
Although the diagnosis of vegetation may be strongly suspected based on its echocardiographic appearance, it is important that the echocardiographic findings be interpreted in clinical context. The differential diagnosis for vegetation includes thrombus, neoplasm such as fibroelastoma (see Fig. 37.4 in Chapter 37 ), mobile calcific elements, aortic valve Lambl excrescences, Libman-Sacks (noninfective) endocarditis, or benign degenerative strands. Less commonly, prosthetic valve suture may be confused with vegetation, as can the variable valve thickening of myxomatous mitral disease or the normal right atrial variants of the eustachian valve or Chiari network. As a rule of thumb, masses with an echotexture similar to that of calcium or the pericardium are unlikely to be vegetations, as are linear strand-like masses that have a narrow attachment to the valve.
It is impossible to identify the infecting organism based on the echocardiographic appearance of vegetations, although fungal vegetations do tend to be large.
Complications of Endocarditis
Complications of endocarditis include those due to the local extension of the infective process and distal complications related to embolus or secondary seeding of distal sites by endocarditis-associated bacteremia.
Abscess, Pseudoaneurysm, and Fistula
Perivalvular abscesses occur due to contiguous spread of infection and are most commonly encountered in the setting of aortic valve or prosthetic valve endocarditis. Involvement of the conduction system may cause atrioventricular conduction disturbances, which may be clinical clues to aortic root or, less commonly, mitral or tricuspid abscess formation.
The echocardiographic appearance of an abscess is one of initial thickening, which typically acquires variable degrees of echolucency with progression ( Fig. 40.5 , , ). Septation and loculation are common. Transthoracic echo has a reported sensitivity of approximately 50% for the detection of abscesses with a sensitivity of up to 90%. For TEE, the sensitivity is 60%–90% with specificity of approximately 90%. For both TTE and TEE, nonstandard views are important and TTE and TEE should be viewed as complementary techniques. For example, TTE may be superior to TEE in identifying anterior aortic root abscesses in the setting of aortic prostheses due to acoustic shadowing by the prosthesis in standard midesophageal TEE views. It is imperative that abscess formation detected or suspected on TTE be followed by TEE for better delineation. The most common location for an abscess is in the vicinity of aortic-mitral intervalvular fibrosa at the junction of the aortic annulus and anterior mitral leaflet. However, abscesses can extend circumferentially and involve any location in the aortic annulus. Mitral annular abscesses are less common in the absence of a prosthetic valve, although mitral annular calcification may be secondarily infected.
It should be noted that the appearance of the aortic root following aortic root repair or homograft/allograft aortic valve replacement may mimic the thickening associated with an abscess, particularly if surgical glue has been used. This underscores the importance of intraoperative postprocedural TEE and subsequent baseline TTE for any valve surgery or root reconstructive procedure.
When the abscess ruptures into the adjacent blood pool, there may be to and fro or unidirectional flow with pseudoaneurysm formation ( Figs. 40.6 and 40.7 , , ). The diagnosis is established with color flow Doppler. In the case of aortic root abscesses, secondary rupture into the left ventricle may also occur with resultant severe regurgitation. If the abscess is extensive it may extend toward the right atrium, right ventricle, or left atrial appendage ( Fig. 40.8 , 
). It may also be associated with infection of adjacent structures, particularly the septal leaflet of the tricuspid valve, which is closely positioned relative to the aortic root. It is essential to use nonstandard images and extend the examination to adjacent structures if one is to capture the full extent of the infectious process.
An abscess may also progress to fistula formation ( Fig. 40.9 , , ) with the abscess creating a communication between the aorta and the atrium or ventricle, or between the cardiac chambers. Fistulae may be in direct communication or have a more serpiginous course, and depending on the size and location of the communication, be associated with catastrophic hemodynamic compromise. Color flow mapping may provide the first echocardiographic clue that a fistula exists and help map out its course.
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