Transesophageal Echocardiography (TEE) in the Evaluation of Infective Endocarditis

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TRANSESOPHAGEAL ECHOCARDIOGRAPHY

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TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) IN THE EVALUATION OF INFECTIVE ENDOCARDITIS Elizabeth W. Ryan, MB, BS, and Ann F. Bolger, MD

Endocarditis is a potentially life-threatening disease. Although it is rare, endocarditis is a common concern in the differential diagnosis of many day-to-day clinical situations, because its many manifestations can mimic other systemic infections and inflammatory states. The annual incidence of endocarditis is increasing, with 20,000 to 30,000 new cases per year, particularly among newborn and elderly patients. The implications for these patients are serious and lifelong, despite advances in antimicrobial therapy and diagnostic and surgical techniques. A time- and cost-efficient strategy for the detection of endocarditis is critical for avoiding long-term sequelae and for prompt management of major systemic complications, including mycotic aneurysms, splenic abscess, and focal ischemia secondary to embolism. Echocardiography is the primary technique for the detection of vegetations and cardiac complications that result from endocardial infection. As imaging has improved, the role of echocardiography in the diagnosis and management of patients with endocarditis has become defined clearly. Formal diagnostic criteria for endocarditis13 recently have been developed to underscore the importance of

echocardiographic findings in establishing or ruling out the presence of endocarditis.

PATHOGENESIS

Abnormalities of endocardial surfaces and flow or host immunity generally are required for the initiation of endocarditis. Infections usually are established in a region exposed to turbulent flow. In these areas, flow velocities are low and disorganized, which leads to endothelial activation and increased propensity to platelet adherence. In native valves, this generally occurs at the edge of a regurgitant orifice where eddy currents alongside the high-velocity jet occur. Alternatively, but less often, vegetations may form at the site of contact between a high-velocity flow and the cardiac wall. In prosthetic valves, vegetations usually arise from the prosthetic ring and along the edge of the origin of a regurgitant or high-velocity flow. Abnormalities that arise from sites other than these, such as the surface of valve leaflets unrelated to a regurgitant or high-velocity flow, are less likely to reflect true infectious vegetation. Once initiated, infection progresses to the

From the Division of Cardiology, Department of Medicine (EWR, AFB), I'arnassus Campus (EWR), University of California, San Francisco; and Echocardiography, Division of Cardiology, San Francisco General Hospital (AFB), San Francisco, California

CARDIOLOGY CLINICS

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formation of vegetation, abscess, valvular destruction, or other mechanical complications. These changes result in new or changing murmurs, valvular insufficiency, ventricular failure, or systemic embolic events. These findings evident on clinical examination should prompt investigation for endocarditis as the source of fever and systemic illness. Underlying Cardiac Conditions

A wide range of congenital or acquired valvular abnormalities increases the risk for infection. These conditions have in common abnormalities of blood flow that create turbulence or endothelial activation or present artificial material surfaces to the blood stream. Endothelialization of prosthetic patch materials, for example, decreases the susceptibility for endocarditis over the first few months after cardiac surgery. Similarly, pacemakers, coronary stents, and implantable defibrillators become endothelialized and do not warrant antibiotic prophylaxis after the initial perioperative period. Abnormal but low-velocity flows, such as with a secundum atrial septal defect, do not seem to be associated with an increased risk for infection because of the absence of significant turbulence. Patients with abnormal aortic and mitral valves (i.e., left-sided valvular defects) seem more susceptible than patients with pulmonary valvular abnormalities, and this likely is related to the higher stenotic or regurgitant velocities of the left heart. Among intravenous drug users, tricuspid valve infection (Fig. 1) is most frequent and probably relates to the greater exposure to high levels of bacterial organisms from direct venous injection. The relative risk for developing endocarditis associated with different underlying cardiac conditions has been outlined by American Heart Association guideline^.^ The highest risk patients include those with prosthetic heart valves or surgically created systemic-pulmonary shunts. Also in this category are patients who have had previous endocarditis at any site; whatever factors put them at risk for their initial infection may still be present, and valvular abnormalities from their first infection may contribute to their ongoing risk for reinfection. This group’s high risk is not only for development of infection but also for serious complications.

A moderate risk category for the development of infective endocarditis includes a much greater proportion of patients. Among these predisposing conditions are congenital valvular stenoses or insufficiency, uncorrected ventricular septal defects, patent ductus arteriosus, coarctation of the aorta, and complex congenital heart defects, including atrioventricular canal defects, single ventricle, transposition of the great arteries, and tetralogy of Fallot. Acquired rheumatic or senescent/ degenerative valvular disease also falls into this moderate risk category, as does hypertrophic cardiomyopathy with outflow tract obstruction and mitral valve prolapse (MVP) with mitral regurgitation. MVP is a relatively common condition, and only the subset of patients with valvular insufficiency seems to be at increased risk. Significant leaflet thickening in MVP seems to correlate with an increased risk for endocarditis and may be a marker of intermittent mitral insufficiency. There has been significant controversy regarding the absolute risk presented by MVP; although this risk may be small, it remains the commonest underlying cardiac condition in adult patients who contract endo~arditis.~ Organisms Adhesion to the endothelium is required for establishment of infection, and the propensity for adhesion is species specific. Typical endocardia1 pathogens are viridans streptococci, Streptococcus bovis, and the HACEK group of fastidious gram-negative organisms (Haemophilus sp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella sp., and Kingella kingae). Staphylococcus aureus or enterococci are more predictive of endocarditis when community acquired or unassociated with an alternative primary focus of infection. s. aureus is particularly virulent, often producing fulminant infection with a complicated clinical course and high mortality. S. epidermidis and other coagulase negative staphylococci are leading causes of prosthetic endocarditis. Care has to be taken in interpretation of blood cultures, as these skin organisms are also common contaminants. Other organisms less frequently responsible for endocarditis include Lactobacillus, Brucella, Listeria, and gonococci. Fungal infection, particularly with Crypotococcus and Candida, is more frequent in patients with impaired immunity.

TEE IN THE EVALUATION OF INFECTIVE ENDOCARDITIS

Figure 1. Tricuspid valve (N) vegetation (arrow) is demonstrated clearly by the transthoracic approach (A). Right-sided cavity dilatation secondaty to severe tricuspid regurgitation also is noted. 13, Transesophageal echocardiography. RV = right ventricle; RA = right atrium; LV = left ventricle; LA = left atrium.

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DIAGNOSIS OF ENDOCARDITIS Duke Criteria

Box 1. Duke Criteria for Diagnosis of Infective Endocarditis

Once endocardial infection is established, Definite Infective Endocarditis systemic bacteremia is continuous. As a rePathological criteria sult, most patients with active endocarditis 1. Microorganisms have the infecting pathogen isolated by blood Demonstrated by culture or histology in a cultures. Unfortunately, in some patients culvegetation or tures are not drawn correctly before antibiotic In a vegetation that has embolized or therapy, and the bacteriologic information In an intracardiac abscess or may be lost. In addition, approximately 5% 2. Pathological lesions Vegetation or intracardiac abscess presto 10% of cases of infective endocarditis are ent confirmed by histology showing ac”culture negative” because of difficulty in cultive endocarditis turing the responsible organism. In all cases, but particularly in those in whom bacterioClinical criteria (using specific definitions logic criteria are unlikely to be met in a timely listed in Table 1) fashion, the echocardiographic detection of 1. 2 major criteria or vegetation or complications of endocarditis is 2. 1 major criterion and 3 minor criteria or of prime importance. 3. 5 minor criteria The Duke criteria (Box l), published in Possible Infective Endocarditis 1994,13 create a diagnostic scheme for the evaluation of the patient suspected of infecFindings consistent with infective endocarditive endocarditis. In these criteria, echocartis that fall short of “definite” but not “rejected.” Proposed clinical criteria (using spediographic findings consistent with vegetacific definitions listed in Table 1) tion or new endocardial infection are major diagnostic criteria (Table 1).The findings of 1. 1 major criterion and 1 minor or intracardiac masses, abscesses (Fig. 2; see 2. 3 minor criteria also Color Plate 2, Fig. 9) with or without Rejected fistulae, new insufficiency, or new peripros1. Firm alternative diagnosis for manifestathetic regurgitation (Fig. 3; see also Color tions of endocarditis or Plate 2, Fig. 10) are considered indicative of 2. Resolution of manifestations of endocardiendocarditis. tis, with antibiotic therapy for 4 days or Although vegetations (Figs. 4-5) are the less or classic pathological finding of endocarditis, 3. No pathological evidence of infective enthey are not uniformly large or easily detectdocarditis at surgery or autopsy after antiable. The earliest vegetations may be mural biotic therapy for 4 days or less as opposed to protuberant and so small as to fall below the threshold for detection by Reprinted from American Journal of Medicine, ultrasound methods. Because the clinical goal Vol 96, Durack DT, Lukes AS, Bright DK: New criteria for diagnosis of infective endocarditis: Utiliis to maximize the early detection of endocarzation of specific echocardiographic findings, pp ditis, the ability to detect even subtle, early 200-209, Copyright 1994, with permission from forms of endocardial infection becomes imExcerpta Medica Inc. portant. Other echocardiographic findings that might be consistent with endocarditis but fall short of the specific evidence listed previously up to 24% of patients with infective endocarare considered minor criteria. Suggested ditis may be misclassified as ”p~ssible.”’~ This modificationsz1to the Duke criteria for 2000, is especially so in culture negative cases. Also, however, recommend deleting this criterion in the absence of supportive echocardiogiven the wide-spread use of transesophageal graphic findings, the diagnosis of endocardiechocardiography (TEE). tis may be difficult to support. False-negative Although the Duke criteria have been valiechocardiographic studies may constitute a dated” and shown to be superior to the clinical disaster for these patients, confusing previously adopted von Reyn criteria for the clinical diagnosis of infective endo~arditis,~~and delaying appropriate treatment.

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Table 1. DEFINITIONS OF TERMINOLOGY USED IN THE DUKE CRITERIA Major Criteria

Minor Criteria

Positive blood cultures Typical microorganisms for endocarditis from two separate blood cultures Persistently positive blood cultures Blood cultures drawn >12 hr apart or All 3 or a majority of 4 or more blood cultures with the first and last at least 1 hr apart Evidence of endocardia1 involvement Positive echocardiogram Oscillating intracardiac mass, on valve or supporting structures, in the path of regurgitant jets, or on implanted material, in the, absence of an alternative explanation or Abscess or New partial dehiscence of prosthetic valve or New valvular regurgitation (increase or change in preexisting murmur not sufficient)

Fever 238.0"C (100.4"F) Predisposition Predisposing heart condition or intravenous drug use Vascular phenomenon Major arterial emboli Septic pulmonary infarcts Mycotic aneurysms Intracranial hemorrhage Conjunctival hemorrhages Janeway's lesions Immunologic phenomena Glomerulonephritis Osler's nodes Roths spots Rheumatoid factor Microbiological evidence Positive blood culture but not meeting major criterion or serological evidence of active infection with organisms consistent with endocarditis Echocardiogram Consistent with infective endocarditis but not meeting major criterion

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Reprinted from American Journal of Medicine, Vol 96, Durack DT, Lukes AS, Bright D K New criteria for diagnosis of infective endocarditis:Utilization of specific echocardiographicfindings, pp 20&209, Copyright 1994, with permission from Excerpta Medica Inc.

Figure 2. A, Perivalvular extension of infection is noted with an abscess cavity (arrow) adjacent to the aortic valve. B, Pseudoaneurysm formation (arrow) is demonstrated by color Doppler imaging showing flow into the abscess cavity. LA = left atrium; RA = right atrium. (See also Color Plate 2, Fig. 9.)

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Figure 3. Prosthetic valvular infection indicated here by partial annular dehiscence (arrow) of this bioprosthetic mitral prosthesis (A), and perivalvular leak noted by color Doppler (B). LA = left atrium; LV = left ventricle. (See also Color Plate 2, Fig. 10.)

Figure 4. A and B, Transesophageal images demonstrate a large mass with soft tissue density (arrow) adherent to the mitral valve. Independent and chaotic motion is usually observed. The vegetation is large enough to produce obstruction to flow with elevation of the mitral inflow gradient. Ao = ascending aortic root; LA = left atrium; LV = left ventricle; RV = right ventricle.

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Figure 5. Transesophageal image demonstrates a small vegetation (arrow) in the left ventricular outflow tract (LVOT) and para-aortic thickening indicative of abscess formation. LA = left atrium.

Transthoracic Echocardiography Transthoracic echocardiography is noninvasive and rapidly achieved. Specificity approximates 98%.18,35 Under optimal imaging conditions, vegetations as small as 2 mm may be detected on native valves.33Infections involving the tricuspid valve are often detected with transthoracic methods (see Fig. lA), as the physical proximity of the valve to the chest wall improves visualization. Transthoracic imaging may be inadequate in up to 20% of adult patients, however, because obesity, pulmonary disease, and chest wall deformity interfere with image quality. For the left-sided valves and prosthetic material, transthoracic imaging has fallen short with respect to sensitivity; overall detection rates for endocarditis are reported below 60%0?4,34* 35 The reduced sensitivity with transthoracic echocardiography may be particularly important in elderly patients.41Imaging windows may be poorer, and there often is difficulty differentiating vegetations from degenerative valvular changes that occur commonly in this age group. The impact of changing technology, such as harmonic imaging with its improved endocardial definition,20on transthoracic detection rates of lesions is yet to be studied. Image enhancement modalities may improve the sensitivity of transthoracic imaging but may also reduce its specificity. There are clearly situations when transtho-

racic echocardiography is an appropriate initial approach in evaluating the patient for endocarditis (Fig. 6).5 Specifically, patients in whom the clinical suspicion for endocarditis is lowz2and who are at low risk for serious complications of an infection if it is present may be appropriate candidates for transthoracic scanning. In this setting, a negative transthoracic study of good quality may prompt a clinical search for other, noncardiac sources of fever. Subsequent TEE can be performed if the clinical picture changes, if there is no improvement on therapy, or if complications are suspected.35In patients at high risk for infective endocarditis or its complications (for example, patients with prosthetic valves, community-acquired Staphylococcal bacteremia, or new atrioventricular block), transthoracic echocardiography is not adequate. Even if transthoracic views demonstrate diagnostic vegetations, transthoracic views are inadequate to exclude the complications of periannular abscess, infection of prosthetic valves, leaflet perforation, and fistulae, which may dictate important management decisions.1,12,34 Transesophageal Echocardiography Transesophageal echocardiography offers the greatest sensitivity for detection of vegetations. The sensitivity of transesophageal imaging approximates 100% on native valves

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Figure 6. An approach to the diagnostic use of echocardiography (echo). IE = infectious endocarditis; TTE = transthoracic echocardiogram; TEE = transesophageal echocardiogram; Rx = antibiotic treatment for endocarditis. *High risk echocardiographic features include large or mobile vegetations, valvular insufficiency, suggestion of perivalvular extension, or secondary ventricular dysfunction. tFor example, a patient with fever and a previously known heart murmur and no other stigmata of IE. *High initial patient risks include prosthetic heart valves, many congenital heart diseases, previous endocarditis, new murmur, heart failure, or other stigmata of endocarditis. (from Bayer AS, Bolger AF, Taubert KA, et al: Diagnosis and management of infective endocarditis and its complications. Circulation 98:2936-2948, 1998; with permission.)

and only slightly less for prosthetic valves, with 86% to 94% sensitivity and 88% to 100% specificity." 11, 12, l9 Compared with transthoracic imaging, the transesophageal approach identifies perivalvular extension of infection (Fig. 7; see Figs. 2 and 5), often occurring around the aortic root and basal septum, with substantially higher sensitivity (76%-100%) and specificity (94%).",19, 29 TEE is safe in experienced handsloand does not routinely require periprocedural antibiotic pro phyla xi^,^ although this may be considered for patients with high-risk cardiac conditions (such as prosthetic valves) or poor dental hygiene. The clinical reliability of the technique for the diagnosis of the infection and its complications makes transesophageal imaging the initial method of choice for many patients suspected of having endocarditis. It is indi-

cated for difficult to image patients, for possible prosthetic valve infection, in patients with intermediate or high clinical suspicion of infective endocarditis, or in patients with a high risk for complications. In patients with S. aureus bacteremia, TEE has been advocated to be essential as part of early evaluation to establish a diagnosis of infective endocarditis and for the detection of complications in these high-risk patients.15 Any suspicion of endocarditis in a patient with prosthetic valves should prompt immediate transesophageal imaging. Similarly suspicion of infection in a patients with indwelling pacemakers or rightheart catheters is an indication for TEE. The improved accuracy of TEE is the result of several factors. First, the removal of interposed chest wall structures improves penetrance of ultrasound from the esophageal

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Figure 7. Paravalvular extension of infection has developed in relation to this aortic bioprosthetic valve (abscess formation) with a vegetation noted in the left ventricular outflow tract (LVOT) (arrow). Ao = ascending aorta.

window. Second, the smaller distances between probe and cardiac structures allow the use of higher ultrasonic frequencies that result in improved spatial resolution. This improvement in resolution not only improves the recognition of pathognomonic features of vegetations, such as independent motion from the valves to which they are attached and color Doppler regurgitant jets, but also improves recognition of several common artifacts and coexisting cardiac structures that may be mistaken for infection. Imaging in two or more planes improves the accuracy of transesophageal The use of multiplane probes facilitates the visualization of structures from multiple angles. Prosthetic materials create imaging barriers because of their reflectance of ultrasound. The transesophageal windows offer a different vantage point from which to inspect the implanted materials. Prosthetic valvular insufficiency may be defined more clearly with transesophageal imaging when interference with Doppler signals is reduced.25 Transesophageal windows are greatly advantageous in the setting of prosthetic mitral valves, because the valvular structures and regurgitant flows are visualized much better from the atrial aspect. In contrast, aortic valve prostheses may create shadows that obscure insufficiency or leaflet morphology from some transesophageal views. Multiple planes

and windows often need to be attempted to fully describe these prostheses, and additional transthoracic views may further assist in defining aortic insufficiency. Concurrent transthoracic images often are helpful when vegetations or other complications are detected on transesophageal studies; they create a baseline for vegetation and chamber sizes that may be helpful for subsequent follow-up of the patient. Imaging Artifacts, False Positives and Negatives

A negative transesophageal study alone does not have the diagnostic accuracy to rule out infective end~carditis.~~ When TEE and transthoracic echocardiographic studies are negative, the negative predictive value is 95%.2* False-negative echocardiographic studies may result by previous embolization of infected material because patients who present with clinical embolism may not demonstrate persistent vegetation. Patients with early infection may have vegetations that are so small as to fall below the detectable limits of resolution. Inadequate views and acoustic shadowing may interfere with detection of small vegetations and abscesses. Therefore, if the clinical suspicion of endocarditis persists, a repeat transesophageal study after 7 to 10

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days to re-evaluate for vegetation or abscess should be considered. Changing Technology

The quality of echocardiographic techniques is improving constantly. Although improvements in resolution may improve the sensitivity of transthoracic and transesophageal imaging, they also are improving visualization of subtle findings that may be confused with vegetation. Most important of these are valve strands, often referred to as Lambl’s excrescences (Fig. 8). Some pathologic series have demonstrated these strands, which consist of elastic and collagenous fibers with endothelial surfaces in more than 50% of native valves. They also have been detected on prosthetic valves, often in the absence of any suggestion of infection. Higher or harmonic frequency and better temporal resolution make them increasingly common findings. Because of their independent motion, they may be mistaken for filamentous vegetations. When they are long or very prominent, it may not be possible to differentiate them from vegetations. Senescent or dystrophic changes on valves are an additional source of potential confusion. Calcification is often nodular and highly

reflective and may either be confused with vegetation or hide an associated vegetation that is less bright. Healed vegetations often appear dense and highly reflective. Myxomatous degeneration, particularly of the mitral valve, may create redundant mitral chordae with exaggerated motion and thickening that can be mistaken for infectious change. The small prosthetic regurgitant jets (”seating puffs”) seen in normally functioning prosthetic valves should not be confused with abnormal paravalvular leaks. In patients with systemic lupus erythematosus or the antiphospholipid syndrome, noninfective vegetations (Libman-Sacks endocarditis) may be noted. In contrast to infective vegetations, these masses are often sessile, heterogeneous in appearance, and without independent motion. Coexistent leaflet thickening also may be noted. Thrombotic vegetations of marantic endocarditis may be identical in appearance to infective vegetations. The presence of spontaneous echocardiographic contrast may support the diagnosis of thrombosis. In these circumstances the strategy for separating true from false findings depends on several factors. Table 2 summarizes key characteristics in the echocardiographic differential of infective endocarditis. Previous echocardiographic examinations always should be

Figure 8. False-positive echo findings: Lambl’s excrescences may be confused with vegetations. These tiny, filamentous, independently mobile densities (arrow) are characteristically noted on the ventricular side of the mitral valve (A) and the aortic (vessel) side of the aortic valve (6). RA = right atrium; RV = right ventricle; LA = left atrium; LV = left ventricle; Ao = ascending aorta.

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Table 2. DIFFERENTIAL DIAGNOSIS OF ECHOCARDIOGRAPHIC FINDINGS Diagnosis

Infective vegetation

Healed or chronic vegetation Noninfective vegetation (Libman-Sacks)

Marantic (thrombotic) endocarditis

Lambl’s excrescence (valve strands)

Chordal structures Degenerative valvular changes Prosthetic valvular regurgitation

Findings

Independently mobile (chaotic motion) Homogeneous appearance Located near a high velocity jet or area of turbulence Usually results in valvular regurgitation Brightly reflective and dense in appearance Sessile verrucous masses Heterogeneous appearance Not independently mobile Often accompanied by leaflet thickening Independently mobile Homogeneous Difficult to distinguish from infective lesions Spontaneous contrast may be present Generally small (<1-2 mm) filamentous structures Independently mobile Often located on the ventricular side of the mitral valve and the aortic side of the aortic valve May be difficult to distinguish from vegetation May be brightly reflective or hypermobile Often associated with valvular regurgitation Often brightly reflective or calcific with thickened leaflets May be associated with valvular stenosis or reduced mobility of leaflets Small intraprosthesis jets (“seating puffs”) are seen in normally functioninR prosthetic valves

reviewed, if available, to determine the chronicity of the abnormalities. Old, healed vegetations may not be differentiated clearly from new active lesions. Underlying flow disturbances that would have created the substrate for endocarditis should be sought and recognized. Prosthetic valves are one of the highest risk conditions for endocarditis, and any abnormality consistent with vegetation should be taken seriously.

that increases mortality and the risk for heart failure and is associated with an increased need for cardiac surgery.8,26~29 Abscesses may make medical therapy less effective and may undermine valves, leading to destruction of native leaflets or dehiscence of prosthetic structures. If abscesses extend through the myocardium, they may cause fistulous tracts and intracardiac shunts that may contribute to hemodynamic instability and heart failure. Abscesses in the mitral annular and subaortic region may extend to involve the region of DETECTION AND MANAGEMENT OF the atrioventricular node, resulting in heart COMPLICATIONS block and arrhythmia. The clinical triad of new regurgitant murmur, pericarditis, and The prognosis of the individual with endohigh-grade atrioventricular block indicates an carditis is influenced greatly by the developincreased likelihood of perivalvular abscess. ment of complications of the infection. The Abscess, pseudoaneurysm, and fistulous size, location, and number of vegetations seen tracts are best detected with TEE,’ which has on TEE may improve prediction of complicahigher sensitivity and specificity than transtions. An increase in vegetation size by serial thoracic imaging for these findings. Abscesses echocardiography over the course of therapy may occur in native valve endocarditis, paralso may identify a subset of patients with a ticularly of the aortic valve (see Fig. 2), but higher rate of complications, independent of are detected most often in patients with prosthe presence of persistent bacteremia or overt clinical stigmata of infective end~carditis.~] thetic valve endocarditis, in whom infections tend to involve the periannular structures. The most important complications of endoBecause of their deep location and proximity carditis are periannular extension of infection, to prosthetic material, abscesses are rarely deembolization, and heart failure. tectable by transthoracic views. Careful transesophageal imaging of the periaortic zone Perivalvular Extension of Infection and region of the posterior mitral annulus is critical to detection of these penetrating Abscess formation is an important strucinfections. Doppler imaging and spectral tural complication of infective endocarditis

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coronary embolization or underlying coronary artery disease that may impair the hemodynamic tolerance of sepsis. Contributing mechanical complications must be identified, because these will not improve with medical therapy alone (such as fistulous tracts, abscess, flail or perforated leaflets, obstructing vegetations, and prosthetic dehiscence). Progressive chamber dilatation and rising pulmonary artery pressure may herald decompensation. Cardiac filling pressures also can be evaluated, using mitral inflow pattern, venous Doppler patterns, inferior vena cava diameter, and other parameters, and may guide medical therapy; however, CHF in patients Congestive Heart Failure with infective endocarditis treated with medical therapy alone portends a grave prognosis. Of all the complications of infective endoIn those patients referred for surgery, CHF is carditis, congestive heart failure (CHF) is the strongest indicator of an adverse pr0gnosis.2~ the most powerful predictor of poor outcome.37Box 2 outlines echocardiographic feaCHF may develop acutely or insidiously despite appropriate antibiotic therapy. Patients with normal ventricular contractile function or only mild CHF at initial diagnosis of infective endocarditis may progress to severe CHF. Box 2. Echocardiographic In two thirds of such patients, progression Features Suggesting occurs during the first month of therapyz3 Potential Need for Surgical Congestive heart failure may result from Intervention prosthetic valve dehiscence, native valvular destruction or perforation, mitral chordal Vegetation Persistent vegetation after systemic emborupture, or valvular obstruction from bulky lization vegetations. Abrupt onset of intracardiac Anterior mitral leaflet vegetation, particushunting by way of fistulous tracts also may larly with size >10 mm* cause acute worsening of CHF. Heart failure One or more embolic events during first is the main indication for surgical interven2 wk of antimicrobial therapy* tion in infective endocarditis and may be a Two or more embolic events during or clinical emergency. Acute severe aortic or miafter antimicrobial therapy* tral insufficiency is poorly tolerated and may Increase in vegetation size after 4 wk of cause sudden death or pulmonary edema. antimicrobial therapyt Careful monitoring of the patient during Valvular dysfunction medical therapy is essential to planning surAcute aortic or mitral insufficiency with gery before these extreme conditions exist. signs of ventricular failuret Important warning signs include tachycardia, Heart failure unresponsive to medical therpoor oxygenation, arrhythmia, or new heart aPYt block. An abrupt change (including a sudden Valve perforation or rupturet diminution) of cardiac murmurs is an omiPerivalvular extension nous sign suggesting progressive valvular deValvular dehiscence, rupture, or fistulat struction. New heart blockt Echocardiography allows delineation of the Large abscess or extension of abscess decauses and severity of CHF and aids managespite appropriate antimicrobial therapyt ment strategies. Transthoracic and transesophageal imaging may demonstrate the 'Surgery may be required because of risk for ernbolization. physiologic consequences of acute valvular $Surgery may be required because of heart failinsufficiency that lead to pulmonary congesure or failure of medical therapy. tion or inadequate cardiac output. Ventricular From Bayer AS, Bolger AF, Taubert KA, et al: size, wall motion, and contractile function can Diagnosisand management of infective endocardibe evaluated, and valvular insufficiency setis and its complications. Circulation 98:29362948, 1998; with permission. verity can be graded. Segmental wall motion abnormalities of the left ventricle may reflect

Doppler velocities are pivotal in identifying valvular insufficiency and fistulous tracts. Pulsatile flow in these abscesses (see Fig. 2) indicates communication with one or more cardiac chambers and pseudoaneurysm (mycotic aneurysm) formation.' Abscesses often progress to fistulae and intracardiac shunts. Inlet and outlet sites of these fistulae may be multiple and should be sought carefully because they may determine the immediate hemodynamic impact of the abscesses and the surgical approach to closing them.

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tures suggesting potential need for surgical intervention. Embolization One of the most difficult aspects of managing patients with endocarditis is estimating the risk for systemic embolization. Embolization occurs frequently in infective endocarditis and often occludes flow to vital territories in the central nervous system (CNS), spleen, kidneys, bowel, and extremities. The mortality of CNS emboli, more than 90% of which lodge in the distribution of the middle cerebral artery, is high.28The embolic potential of any given vegetation is impossible to predict accurately, but the specific organism, site, size, and motion may influence its beha~i0r.l~ Infection on the left-sided valves is most relevant to systemic embolization. S. aureus, Candida, and HACEK infections have the highest incidence of embolization, and this may be independent of vegetation size. Large vegetations resulting from streptococcal infection are uncommon, but one study36indicated that when they achieve this size, they have a high potential for embolization. There are other indications that vegetation size may impact embolic risk. Vegetations on the mitral valve with a diameter of more than 1 cm by transesophageal imaging have been shown to have a higher incidence of embolization than smaller vegetation^.^^ In addition, increasing vegetation size during the course of antibiotic therapy doubled the embolic risk compared with patients with static or decreasing size.30Location also may impact on embolization, with mitral valve involvement posing a higher risk than an aortic site. The best therapy to minimize embolic risk seems to be early and effective antibiotic therDuring the first 2 weeks of successful antibiotic therapy, the rate of embolic events falls from 13 to less than 1.2 embolic events per 1000 patient-days. Surgery to remove vegetations and hopefully decrease the risk of embolization is of greatest benefit during the early weeks of treatment. Pericarditis Although not a finding specific to infective endocarditis, pericardial effusion may occur as part of the clinical spectrum. Hematogenous seeding, rupture of myocardial abscess,

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or perforation of perivalvular abscess or pseudoaneurysm may result in purulent pericardial effusion in acute infections.40Reactive serous effusion occasionally may develop with subacute infective endocarditis. INTRAOPERATIVE ASSESSMENT Transesophageal imaging generally is performed during valve surgery in the setting of endocarditis. Careful definition of abscess cavities and fistulous tracts allows complete dkbridement and repair. Extensive destruction of the periannular tissues may indicate more complex surgical approaches or direct the choice of prosthetic materials. Human aortic allografts, which may be implanted with variable amounts of the contiguous aortic tissue, can be used to replace the damaged aortic valve and reconstruct the aorta.16,32 Post-cardiopulmonary bypass images help to confirm the adequacy of the repair and competence of the prosthetic replacement. FOLLOW-UP OF PATIENTS WITH PREVIOUS INFECTIVE ENDOCARDITIS Most patients have persistent vegetations demonstrable by echocardiography after completion of treatment for endocarditis. In the absence of symptoms of ongoing infection or evidence of severe valvular insufficiency, the presence of these presumably healed vegetations (Fig. 9) does not predict late complic a t i o n ~ Echocardiography .~~ is not indicated to confirm resolution of infection. For those patients whose course was complicated by ventricular enlargement or dysfunction, significant valvular insufficiency, or who underwent valve surgery, however, posttreatment echocardiography may provide an important baseline for long-term follow-up. SUMMARY Echocardiography is an essential tool for the modern diagnosis and management of infective endocarditis and its complications. The negative predictive value of surface imaging is inadequate to rule out endocarditis in most instances; diagnostic sensitivity is improved by way of the transesophageal approach. The clinical scenario and pretest prob-

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Figure 9. Healed vegetations become smaller and echo bright, suggesting calcification, as noted in this transesophageal image of treated mitral valve endocarditis. LA = left atrium; LV = left ventricle; MV = mitral valve.

ability of disease should guide the use of transesophageal versus transthoracic imaging. Those at high risk for endocarditis or its complications in particular should undergo early TEE. Serial studies may be required to guide management. In the setting of an initially negative echocardiographic study, a repeat examination is indicated if the clinical suspicion of endocarditis persists or if the clinical picture changes. Combined transthoracic echocardiography and TEE may supply complementary information useful in management and follow-up. As most published research predates recent advances in imaging, the impact of changing technology, such as harmonic and three-dimensional imaging, in the management of endocarditis is yet to be determined.

References Afridi I, Apostolidou MA, Saad RM, et al: Pseudoaneurysms of the mitral-aortic intervalvular fibrosa: Dynamic characterization using transesophageal echocardiographic and Doppler techniques. J Am Coll Cardiol25:137-145, 1995 Ali AS, Trivedi V, Lesch M: Culture-negative endocarditis: A historical review and 1990s update. Prog Cardiovasc Dis 27149-160, 1994

3. Bayer AS: Infective endocarditis. Clin Infect Dis 17313-320, 1993 4. Bayer AS, Ward JI, Ginzton LE, et al: Evaluation of new clinical criteria for the diagnosis of infective endocarditis. Am J Med 96211-219, 1994 5. Bayer AS, Bolger AF, Taubert KA, et al: Diagnosis and management of infective endocarditis and its complications. Circulation 98:293&2948, 1998 6. Birmingham GD, Rahko PS, Ballantyne R Improved detection of endocarditis with transesophageal echocardiography. Am Heart J 123:774-781, 1992 7. Cecchi E, Parrini I, Chinaglia A, et al: New diagnostic criteria for infective endocarditis: A study of sensitivity and specificity. Eur Heart J 18:1149-1156, 1997 8. Croft CH, Woodward W, Elliott A, et al: Analysis of surgical versus medical therapy in active complicated native valve infective endocarditis. Am J Cardiol 51:1650-1655, 1983 9. Dajani AS, Taubert KA, Wilson W, et al: Prevention of bacterial endocarditis: Recommendations by the American Heart Association. JAMA 2771794-1801, 1997 10. Daniel WG, Erbel R, Kasper W, et al: Safety of transesophageal echocardiography: A multicenter survey of 10,419 examinations. Circulation 83:817-821, 1991 11. Daniel WG, Mugge A, Martin RP, et al: Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med 324795-800, 1991 12. Daniel WG, Mugge A, Grote J, et al: Comparison of transthoracic and transesophageal echocardiography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions. Am J Cardiol 71:210-215, 1993 13. Durack DT, Lukes AS, Bright DK New criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings. Am J Med 96:200209, 1994 14. Erbel R, Rohmann S, Drexler M, et al: Improved diagnostic value of echocardiography in patients with infective endocarditis by transesophageal approach: A prospective study. Eur Heart J 943-53, 1988 15 Fowler VG Jr, Li J, Corey R, et al: Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: Experience in 103 patients. J Am Coll Cardiol 30:1072-1078, 1997 16 Glazier JJ,Verwilghen J, Donaldson RM, et al: Treatment of complicated prosthetic aortic valve endocarditis with annular abscess formation by homograft aortic root replacement. J Am Coll Cardiol 1711771182, 1991 17. Habib G, Derumeaux G, Avierinos JF, et al: Value and limitations of the Duke criteria for the diagnosis of infective endocarditis. J Am Coll Cardiol 33:202% 2029, 1999 18. Irani WN, Graybum PA, Afridi I: A negative transthoracic echocardiogram obviates the need for transesophageal echocardiography in patients with suspected native valve active infective endocarditis. Am J Cardiol 78:lOl-103, 1996 19. Karalis DG, Bansal RC, Hauck AJ, et al. Transesophageal echocardiographic recognition of subaortic complications in aortic valve endocarditis: Clinical and surgical implications. Circulation 86:353-362, 1993 20. Kombluth M, Liang DH, Paloma A, et al: Native tissue harmonic imaging improves endocardia1 border definition and visualization of cardiac structures. J Am SOCEchocardiogr 11:693-701, 1998

TEE IN THE EVALUATION OF INFECTIVE ENDOCARDITIS 21. Li JS, Sexton DJ, Mick N, et al: Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 30:633-638, 2000 22. Lindner JR, Case A, Dent JM, et al: Diagnostic value of echocardiography in suspected endocarditis. An evaluation based on pretest probability of disease. Circulation 93:730-736, 1996 23. Mills J, Utley J, Abbott J: Heart failure in infective endocarditis: Predisposing factors, course and treatment. Chest 66:151-157, 1974 24. Mugge A, Daniel WG, Gunter F, et al: Echocardiography in infective endocarditis: Reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol 14631-638, 1989 25. Nellessen U, Schnittger I, Appleton CP, et al: Transesophageal two-dimensional echocardiography and color Doppler flow velocity mapping in the evaluation of cardiac valve prostheses. Circulation 78:848855, 1988 26. Omari B, Shapiro S, Ginzton L, et al: Predictive risk factors for periannular extension of native valve endocarditis: Clinical and echocardiographic analyses. Chest 96:1273-1279, 1989 27. Pelletier LL, Petersdorf RG: Infective endocarditis: A review of 125 cases from the University of Washington Hospitals, 196S1972. Medicine 6:287-313, 1977 28. Pruitt AA, Rubin RH, Karchmer AW, et al: Neurologic complications of bacterial endocarditis. Medicine 57329-343, 1978 29. Rohmann S, Seifert T, Erbel R, et al: Identification of abscess formation in native-valve infective endocarditis using transesophageal echocardiography: Implications for surgical treatment. Thorac Cardiovasc Surg 39:273-280, 1991 30. Rohmann S, Erbel R, Darius H, et al: Prediction of rapid versus prolonged healing of infective endocar-

31.

32. 33. 34. 35.

36. 37. 38. 39. 40.

41.

787

ditis by monitoring vegetation size. J Am SOCEchocardiogr 4465474, 1991 Rohmann S, Erbel R, Gorge G, et al: Clinical relevance of vegetation localization by transoesophageal echocardiography in infective endocarditis. Eur Heart J 13:44&452, 1992 Ross D: Allograft root replacement for prosthetic endocarditis. J Cardiac Surg 5:68-72, 1990 Roy P, Tajik AJ, Guilliani ER, et al: Spectrum of echocardiographic findings in bacterial endocarditis. Circulation 533474432, 1976 Shapiro SM, Young E, De Guzman S, et al: Transesophageal echocardiography in diagnosis of infective endocarditis. Chest 105:377-382, 1994 Shively BK, Gurule FT, Roldan CA, et al: Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis. J Am Coll Cardiol 18:391-397, 1991 Steckelberg JM, Murphy JG, Ballard D, et al: Emboli in infective endocarditis: The prognostic value of echocardiography. Ann Intern Med 114635440,1991 Stinson EB: Surgical management of infective endocarditis. Prog Cardiovasc Dis 22:145-168, 1979 von Reyn CF, Levy BS, Arbeit RD, et al: Infective endocarditis: An analysis based on strict case definitions. Ann Intern Med 94:505-517, 1981 Vuille C, Nidorf M, Weyman AE, et al: Natural history of vegetations during successful medical treatment of endocarditis. Am Heart J 128:1200-1209,1994 Weinstein L: Infective endocarditis. In Braunwald E (ed): Heart Disease: A Textbook of Cardiovascular Medicine, ed 3. Philadelphia, WB Saunders, 1988, pp 1093-1134 Werner GS, Schulz R, Fuchs JB, et al: Infective endocarditis in the elderly in the era of transesophageal echocardiography: Clinical features and prognosis compared with younger patients. Am J Med 100:9097, 1996

Address reprint requests to AM F. Bolger, MD Division of Cardiology 5G1 San Francisco General Hospital 1001 Potrero Avenue San Francisco, CA 94110 e-mail: [email protected]