Multislice Computed Tomography in Infective Endocarditis

Transcription

1 Journal of the American College of Cardiology Vol. 53, No. 5, by the American College of Cardiology Foundation ISSN /09/$36.00 Published by Elsevier Inc. doi: /j.jacc Multislice Computed Tomography in Infective Endocarditis Comparison With Transesophageal Echocardiography and Intraoperative Findings Gudrun M. Feuchtner, MD, PD,* Paul Stolzmann, MD, Wolfgang Dichtl, MD, PHD, PD, Thomas Schertler, MD, Johannes Bonatti, MD, FECTS, Hans Scheffel, MD, Silvana Mueller, MD, André Plass, MD, Ludwig Mueller, MD, Thomas Bartel, MD, PD, Florian Wolf, MD, Hatem Alkadhi, MD, PD Innsbruck and Vienna, Austria; and Zurich, Switzerland Objectives Background Methods Results Conclusions The aim of this study was to assess the value of multislice computed tomography (CT) for the assessment of valvular abnormalities in patients with infective endocarditis (IE) in comparison with transesophageal echocardiography (TEE) and intraoperative findings. Multislice CT has recently shown promising data regarding valvular imaging in a 4-dimensional fashion. Thirty-seven consecutive patients with clinically suspected IE were examined with TEE and 64-slice CT or dualsource CT. Twenty-nine patients had definite IE and underwent surgery. The diagnostic performance of CT for the detection of evident valvular abnormalities for IE compared with TEE was: sensitivity 97%, specificity 88%, positive predictive value (PPV) 97%, and negative predictive value (NPV) 88% on a per-patient basis (n 37; excellent intermodality agreement 0.84). CT correctly identified 26 of 27 (96%) patients with valvular vegetations and 9 of 9 (100%) patients with abscesses/pseudoaneurysms compared with the intraoperative specimen. On a per-valve based analysis, diagnostic accuracy for the detection of vegetations and abscesses/pseudoaneurysms compared with surgery was: sensitivity 96%, specificity 97%, PPV 96%, NPV 97%, and sensitivity 100%, specificity 100%, PPV 100%, NPV 100%, respectively, without significant differences as compared with TEE. Vegetation size measurements by CT correlated (r 0.95; p 0.001) with TEE (mean mm). The mobility of vegetations was accurately diagnosed in 21 of 22 (96%) patients with CT, but all of 4 leaflet perforations ( 2 mm) were missed. CT provided more accurate anatomic information regarding perivalvular extent of abscess/pseudoaneurysms than TEE. Multislice CT shows good results in detecting valvular abnormalities in IE and could be applied in pre-operative planning and exclusion of coronary artery disease before surgery. (J Am Coll Cardiol 2009;53:436 44) 2009 by the American College of Cardiology Foundation Infective endocarditis (IE) represents a severe disease with a high mortality rate of up to 40% (1). Despite continuous advances in medical health care, the prevalence of IE has not declined over the past 30 years. In contrast, a recent rise in the prevalence of IE has been reported and explained by increasing predisposing factors such as degenerative valvular From the Departments of *Radiology II, Cardiology, and Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria; Institute of Diagnostic Radiology and Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland; and the Department of Radiology, Vienna Medical University, Vienna, Austria. This research was supported by the National Center of Competence in Research, Computer Aided and Image Guided Medical Interventions of the Swiss National Science Foundation. Manuscript received October 1, 2007; revised manuscript received December 19, 2007, accepted January 6, disease, implanted pacemakers and defibrillators, and prosthetic valves, all of which are enhanced by a general increase in the elderly population. In clinical practice, the diagnosis of IE is often difficult, and both overdiagnosis and underdiagnosis are observed (2). The diagnosis of IE is established using the modified Duke criteria based on clinical and imaging findings (3). Echocardiography represents the central tenant in evaluating patients who have a clinical presentation that raises the concern for IE. With echocardiography, there are several findings that provide evidence of IE, including vegetations, evidence of periannular tissue destruction, abscesses, aneurysms, fistulas, leaflet perforations, or valvular dehiscence. Transthoracic echocardiography (TTE) has shown limited

2 JACC Vol. 53, No. 5, 2009 February 3, 2009: Feuchtner et al. Multislice CT in Infective Endocarditis 437 sensitivity for the diagnosis of IE ranging between 18% and 63% (4) with a detection rate of 25% for small vegetations 5 mm(5). Therefore, transesophageal echocardiography (TEE) is usually also performed. Based on its higher specificity and sensitivity ranging between 48% to 100% (4), TEE is considered the reference imaging method. Nevertheless, both TTE and TEE are limited by their dependence on the individual patient s morphology, instrumental settings, transducer position, operator, and artifacts from heavy valve calcifications and metallic prosthetic valves through acoustic shadowing. Therefore, if an initial echocardiography is negative, repeated TEE examinations are recommended in cases of clinical suspicion (6,7). Recent advances in the temporal and spatial resolution of multislice computed tomography (CT) scanners allow highresolution cardiac imaging. Currently, the major application of multislice CT is the evaluation of coronary artery disease to exclude coronary stenosis 50% (8,9). In addition, CT has recently shown promising results in valvular imaging (10 13) by providing morphologic information and functional 4-dimensional cine-imaging. Thus, cardiac multislice CT could qualify as an alternative imaging modality for visualizing valvular abnormalities in IE, and therefore, the purpose of this study was to compare CT with TEE and intraoperative findings. Methods Study population. Between August 2006 and September 2007, 37 consecutive patients with suspected IE were examined. The diagnosis of IE was based on the modified Duke criteria (2,3). According to Haldar and O Gara (2), definitive IE (n 29) was defined as the presence of either 2 major criteria or 1 major and 3 minor criteria. Possible IE (n 8) was defined as the presence of either 1 major (positive hemoculture with specific bacteria) and 1 minor (n 4) or 3 minor criteria (n 4) out of the following: positive hemoculture with nonspecific microorganism, fever 38 C, predisposing cardiac conditions (e.g., prosthesis, valvular disease) or intravenous drug abuse, immunologic phenomena, or vascular phenomena. CT was performed on the same day as (n 27) or 1 day after (n 10) echocardiography. Twenty-eight patients underwent surgery within 5 days after CT, 1 patient was operated on 6 weeks later because of comorbidities. All cardiac CT examinations were clinically indicated. Reasons for referrals to CT were exclusion of coronary artery disease (n 31) and/or uncertain echocardiography findings regarding anatomic extent of extravalvular involvement (n 12) and the assessment of coronary bypass patency (n 1). Patient exclusion criteria were renal dysfunction (serum creatinine 1.5 mg/dl), hyperthyroidism, iodine allergy, New York Heart Association functional class III to IV heart failure, and pregnancy. Within the time period of data acquisition, 8 patients were excluded because of nephropathy (n 4), iodine allergy (n 2), New York Heart Association functional class IV heart failure (n 1), and emergency surgery before the CT scan (n 1). The institutional review board approved the study, and written informed consent was obtained. Multislice CT. CT SCAN PROTO- COL. Twenty patients underwent imaging with a 64-slice CT scanner (Sensation 64, Siemens, Munich, Germany) using the following parameters: detector collimation mm, slice acquisition mm by means of z-flying focal spot, pitch 0.2, gantry rotation time 330 ms, tube voltage 120 kv, and Abbreviations and Acronyms CI confidence intervals CT computed tomography IE infective endocarditis NPV negative predictive value PPV positive predictive value RCA right coronary artery TEE transesophageal echocardiography TTE transthoracic echocardiography tube-current-time product 600 to 800 mas. Seventeen patients underwent imaging with a dual-source CT scanner (Somatom Definition, Siemens): detector collimation mm, slice acquisition mm, pitch 0.2 to 0.53 (depending on heart rate), gantry rotation time 330 ms, tube voltage 120 kv, and tubecurrent-time product 350 mas/rotation. With 64-slice CT, a beta-blocker was administered intravenously (5 to 10 mg metoprolol) before the examination in patients with heart rates 75 beats/min; no heart rate control was performed in the patients undergoing dual-source CT. The scan direction was cranio-caudal during midinspiration. The scan ranged from pulmonary artery bifurcation level to the heart base. The echocardiogram signal was recorded simultaneously, and echocardiogram-gated dose modulation was used. A bolus of 80 to 100 ml of iodinated contrast agent (Iodixanol, Visipaque 320, GE Healthcare, Buckinghamshire, United Kingdom) followed by a 40-ml saline flush was intravenously injected into an antecubital vein at a flow rate of 5 ml/s. The scan delay was calculated using the bolus-tracking technique (ascending aorta, threshold 100 HU). A dedicated contrast agent injection protocol for both left and right ventricular enhancement was applied in patients with pacemakers (14). CT IMAGE RECONSTRUCTION. Two transverse image sets (A and B) were reconstructed (slice thickness 0.75 mm, increment 0.4 mm, medium-smooth convolution kernel, retrospective electrocardiogram gating during mid-systole to late systole [10% to 40%] and mid-diastole to late diastole [60% to 80%]). Another dataset (C) containing transverse images was reconstructed in 10% steps from 0% to 90% of the cardiac cycle (slice thickness 1.0 mm, increment 0.7 mm). CT IMAGE POST-PROCESSING AND ANALYSIS. The postprocessing was performed on a separate workstation (Leonardo, Siemens).

3 438 Feuchtner et al. JACC Vol. 53, No. 5, 2009 Multislice CT in Infective Endocarditis February 3, 2009: The valves were evaluated according to the following echocardiographic criteria (4): 1. Vegetations, defined as irregularly shaped, oscillating masses, adherent to and distinct from the endocardium; their sizes were measured on multiplanar reformations using an electronic caliper. 2. Abscesses, defined as irregularly shaped, inhomogeneous paravalvular masses within periannular region, myocardium, or pericardium; a pseudoaneurysm was defined as a space filled with contrast medium with a communication with the cardiac chambers or the aortic root. 3. Fistula, defined as a continuation between the chambers of the left and right heart. 4. Leaflet perforation, defined as a discontinuation. 5. Valvular dehiscence, defined as a rocking motion of a prosthetic valve with an excursion 15 in any 1 plane. Image sets A and B were analyzed on multiplanar reformations and by volume rendering technique. Image set C was used for 4-cine dynamic imaging. The CT data analysis was performed by 2 experienced, independent readers blinded to the echocardiography. For intraobserver agreement of CT findings, 2 readers reanalyzed the blinded data after 2 months, and consensus readout was appended in the case of disagreement. Coronary arteries were evaluated with regard to significant coronary stenosis 50%. The valves were assessed regarding aortic stenosis (10) or regurgitation (11), and mitral stenosis (12) or regurgitation (13). Echocardiography. The TEE examinations were performed by 2 experienced reviewers according to a standardized database/reporting system. A multiplane 5-MHz TEE probe (Sonos 5500, Philips Company, Andover, Massachusetts) was used in 20 patients, a multiplane 2- to 7-MHz TEE transducer (Acuson Sequoia 512, Acuson-Siemens Medical Systems, Munich, Germany) in 17 patients. Doppler B- and M-mode capabilities were applied. Echocardiographers were blinded to the results from CT but fully aware of the clinical history. Cardiac surgery. Twenty-nine patients underwent cardiac surgery. The indication of surgery was based on the American Heart Association guidelines (15). The surgeons evaluated valve abnormalities by direct visualization, digital inspection, and instrumental exploration. Surgical criteria for IE were vegetations, leaflet perforations, and/or abscesses, which were subsequently confirmed by histopathology. Perivalvular involvement was evaluated regarding annulus destruction and/or myocardial and pericardial involvement. Surgery consisted of valve replacement or repair in patients with infection limited to the valvular leaflets or of radical resection of infected paravalvular tissues and reconstruction with patches and valve replacement in patients with abscesses. Statistical analysis. The first part of the statistics assessed the value of CT for the diagnosis of IE in comparison with TEE. All patients with definite and possible IE (2,15) were included. Surgery as validation of the imaging findings was not available because patients with possible IE but negative imaging findings were not operated on. The second part included assessment of the diagnostic performance of CT and TEE in comparison with the gold standard, surgery. The diagnostic accuracy of CT was calculated, and differences among CT, TEE, and intraoperative findings were tested for significance by using the McNemar test. Intraobserver agreement for CT readout and intermodality agreement were tested with Cohen s kappa statistics (16). Pearson correlation coefficients were used to compare CT measurements of vegetations with TEE. A value of p 0.05 was considered significant for all tests. The statistical analysis was performed using SSPS version 12.0 (SSPS Inc., Chicago, Illinois). Results Multislice CT was successfully performed in all 37 patients. Patient demographics and clinical data are listed in Table 1. Infective endocarditis involved the mitral and/or aortic valve in 28 of 29 (97%) patients with definite IE. In 1 (3%) patient, IE involved the tricuspid valve and the right ventricular pacemaker lead. Thus, a total of 57 valves (28 mitral, 28 aortic, and 1 tricuspid) were included in the comparative analysis between CT and TEE, taking intraoperative findings as gold standard. Fifty-one of 57 (89%) Study Population (n 45) Table 1 Study Population (n 45) No. of Patients Excluded patients 8/45 (18%) Renal dysfunction 4/45 (9%) Emergency surgery 1/45 (2%) Heart failure (NYHA functional class IV) 1/45 (2%) Hypersensitivity to iodinated contrast media 2/45 (4%) Included patients 37/45 (82%) Possible IE 8/37 (22%) 1 minor, 1 major (positive hemoculture) 4/8 (50%) 3 minor criteria 4/8 (50%) Definite IE 29/37 (78%) Mean age, yrs (range) (20 84) Sex Female 11/37 (30%) Male 26/37 (70%) Mean heart rate during CT, beats/min (range) 68 7 (53 90) Mean heart rate during TEE, beats/min (range) 71 8 (58 86) Heart rhythm during CT scan Sinus rhythm 36/37 (97%) Atrial fibrillation 1/37* (3%) Pre-excitations 7/37 (19%) Use of beta-blockers before CT scan 8/37 (22%) *Regular conduction, therefore sufficient image quality was achieved. Echocardiogram editing was applied to avoid misregistration artifacts. CT computed tomography; IE infective endocarditis; NYHA New York Heart Association; TEE transesophageal echocardiography.

4 JACC Vol. 53, No. 5, 2009 February 3, 2009: Feuchtner et al. Multislice CT in Infective Endocarditis 439 valves were native, and 6 of 57 (11%) were prosthetics (3 of 6 mechanical and 3 of 6 bioprosthetic). The results of intraoperative findings compared with CT are shown in Table 2. Intraobserver and interobserver readout of CT findings. The interobserver agreement for diagnosis of IE (vegetation and/or abscess) per patient was 0.94, and the intraobserver agreement was 1. For the detection of vegetations, abscesses, fistulae, and mobility of vegetations, the intraobserver agreement was 1 and the interobserver agreements were 0.96, 1, 1, and 0.94, respectively. Because of the low interobserver variability, the consensus reading was taken for all subsequent analyses. CT versus TEE in patients with possible and definite IE. In 37 patients with possible or definite IE, CT identified 28 of 29 (97%) patients who had valve abnormalities that were identified by TEE (agreement: 0.84). CT correctly classified 70 of 73 (96%) valves to have abnormalities indicating IE or not (intermodality agreement: 0.92). The diagnostic accuracy of CT compared with TEE on the per-patient and per-valve based analysis is shown in Table 3. CT versus TEE for size and mobility of vegetations and dehiscence. Mean size of vegetations at CT ( mm, range 2 to 22 mm) significantly correlated (r 0.95, p 0.001) with TEE ( mm, range 1 to 22 mm). The mobility of valvular vegetations was diagnosed by CT in 22 of 23 (96%) patients by applying 4-dimensional cine imaging (intermodality agreement: 0.96). CT correctly diagnosed 1 dehiscent mechanic aortic valve prosthesis. CT and TEE versus surgery for vegetations. In 29 patients, CT correctly identified 26 of 27 (96%) patients who had intraoperatively proven vegetations (agreement: 0.78). CT correctly classified 55 of 57 (96%) valves to be either affected by vegetations or not, as confirmed during surgery (agreement: 0.93). On a per-valve based analysis, the diagnostic accuracy of CT compared with surgery was: sensitivity 96%, specificity 97%, PPV 96%, NPV 97% (Table 3). CT depicted 41 of 46 (89%) vegetations when compared with intraoperative findings, but 5 vegetations were missed. Intraoperative Findings in 29 Patients With Definite Infective Endocarditis Table 2 Intraoperative Findings in 29 Patients With Definite Infective Endocarditis Patient # Valve No. of Vegetations Abscess/Pseudoaneurysm Other Findings 1 Bio AV 0 An, Myo 2 MV 2 3 MV 1 1* 4 Mech AV 0 An, Myo 5 MV 2 1* 6 MV-R 1 1* 7 Mech AV 2 An, AR 8 AV 3 Cusp perforation* 9 AV 1 An, Myo Fistula from LV to RV 10 MV 2 11 AV 1* An, Myo 12 MV 1 13 AV 1 14 MV 1 An, Myo, P, CS Leaflet perforation* 15 MV LA 5 Leaflet perforation* 16 AV 1 17 AV MV MV PM-RV TV PM-RV 1 1* 0 21 AV 1 0 An, AR 22 Bio AV 1 An, AR 23 Bio MV Mech AV 1 An, Myo 25 AV 2 26 MV 1 Leaflet perforation* 27 MV 1 28 MV 2 29 AV 2 *Missed by computed tomography. Missed by transesophageal echocardiography. Calcification mistaken by transesophageal echocardiography as noncalcified vegetation. False-positive rating of a vegetation by computed tomography. An annulus; AR aortic root pseudoaneurysm; AV aortic valve; Bio biologic tissue valve; CS coronary sinus; LA left atrium; LV left ventricle; Mech mechanic; MV mitral valve; MV-R reconstructed mitral valve; Myo myocardium; P pericardium; PM pacemaker leads; RV right ventricle; TV tricuspid valve.

5 440 Feuchtner et al. JACC Vol. 53, No. 5, 2009 Multislice CT in Infective Endocarditis February 3, 2009: Diagnostic Performance of CT Table 3 Diagnostic Performance of CT Percent 95% CI For the Detection of Vegetations, Paravalvular Abscesses, and Pseudoaneurysms (37 Patients, 73 Valves) in Patients With Possible and Definite IE: Comparison With TEE Per-patient based analysis Sensitivity (28/29) 97 82% 100% Specificity (7/8) 88 47% 100% Positive predictive value (28/29) 97 82% 100% Negative predictive value (7/8) 88 47% 100% Diagnostic accuracy (35/37) 95 82% 100% Per-valve based analysis Sensitivity (28/29) 97 82% 100% Specificity (42/44) 95 85% 99% Positive predictive value (28/30) 93 78% 99% Negative predictive value (41/42) 98 88% 100% Diagnostic accuracy (70/73) 96 88% 99% For the Detection of Vegetations in Patients With Definite IE (29 Patients, 57 Valves): Comparison With Intraoperative Findings Per-valve based analysis Sensitivity (26/27) 96 81% 100% Specificity (29/30) 97 83% 100% Positive predictive value (26/27) 96 81% 100% Negative predictive value (29/30) 97 83% 100% Diagnostic accuracy (55/57) 96 88% 100% CI confidence interval; CT computed tomography; IE infective endocarditis; TEE transesophageal echocardiography. One of these 5 vegetations (3 mm) was missed by CT because of artifacts. CT missed 3 small mitral valve vegetations ( 4 mm). One vegetation of the tricuspid valve was missed by CT because of low right ventricular contrast enhancement and metallic artifacts of a right ventricular pacemaker lead. One mobile aortic valve vegetation suspected by TEE was a mobile calcification by CT confirmed during surgery. Two vegetations on a mechanical prosthesis were correctly diagnosed with CT but were not depicted by TEE because of metal artifacts. One degenerative mitral valve leaflet thickening in a patient with aortic valve endocarditis was falsely classified as additional vegetation by CT. One aortic valve prolapse of a right coronary cusp was mistaken as a vegetation. TEE correctly identified 26 of 27 (96%) patients with intraoperatively proven vegetations. The diagnostic accuracy of TEE for diagnosis of vegetations on a per-patient ( 0.78) and per-valve ( 0.97) based analysis compared with surgery was: sensitivity 96%, specificity 100%, PPV 100%, NPV 67%, and 96%, 100%, 100%, 97%, respectively. Slight differences in accuracy for the detection of vegetations were found between CT and TEE on a per-valve based analysis without a statistically significant difference (p NS), and accuracy of vegetation detection on a per-patient basis was similar. Figure 1 Mobile Mitral Valve Vegetation With Paravalvular Abscess/Pseudoaneurysm Multislice computed tomography (A: left sagittal oblique; B: axial oblique; C: short-axis view) improved evaluation by showing myocardial breakthrough into pericardium (P), coronary sinus (CS) obstruction. The black arrow (A) is pointing at mobile vegetation (Online Video 1). The white (B) and black arrows (C) delineate the outer border of pericardial inflammatory abscess/effusion. Transesophageal echocardiography (D) detected the abscess/pseudoaneurysm, but the extent of perivalvular involvement was unclear. A abscess; LA left atrium; LV left ventricle; RV right ventricle.

6 JACC Vol. 53, No. 5, 2009 February 3, 2009: Feuchtner et al. Multislice CT in Infective Endocarditis 441 CT and TEE versus surgery for abscess and pseudoaneurysm in patients with definite IE. Nine of 9 (100%) paravalvular abscesses and/or pseudoaneurysms were correctly identified by CT compared with surgery (7 of 9 combined abscesses/pseudoaneurysms, 1 isolated aortic root abscess, and 1 aortic root pseudoaneurysm). On a per-valve based analysis, the diagnostic performance of CT for the detection of abscesses/pseudoaneurysms combined was: sensitivity 100%, specificity 100%, PPV 100%, and NPV 100%. TEE correctly revealed 8 of 9 (89%) paravalvular abscesses and pseudoaneurysms, whereas 1 pseudoaneurysm was missed with TEE. The diagnostic accuracy of TEE for the detection of paravalvular abscesses and pseudoaneurysms in comparison with the intraoperative findings on a per-valve based analysis was: sensitivity 89% (95% confidence interval [CI]: 52% to 100%), specificity 100% (95% CI: 93% to 100%), PPV 100% (95% CI: 63% to 100%), and NPV 98% (95% CI: 89% to 100%). Slight differences in accuracy of CT and TEE for abscess and pseudoaneurysm detection were found on a per-valve based analysis without statistical significance (p NS). CT was superior to TEE for showing the perivalvular involvement of abscesses and pseudoaneurysms in 3 patients. CT more often correctly showed the myocardial (n 6byCT vs. n 3 by TEE), pericardial (n 1byCTvs.n 0by TEE), and coronary sinus involvement (n 1byCTvs.n 0 by TEE) compared with echocardiography. CT correctly identified annulus involvement in 6 of 9 (67%) patients and correctly ruled out annulus involvement in 1 patient in whom extravalvular involvement was inconclusive at TEE. In 3 patients, pseudoaneurysms were located close to the right coronary artery (RCA). In 1 patient, the RCA could not be cannulated with invasive angiography, and exclusion of coronary artery disease was based on CT alone. In the other 2 patients, 3-dimensional visualization of the extent of pseudoaneurysms was useful for pre-operative planning of RCA bypass grafting. CT and TEE versus surgery for fistula and cusp perforation. One of 26 (4%) patients had a fistula from the left ventricular outflow tract through the membranous ventricular septum to the right ventricle correctly diagnosed with both CT and TEE. None of the 4 (0%) intraoperatively confirmed mitral valve leaflet perforations ( 2 mm) could be visualized with CT but were detected by TEE. CT and echocardiography images of patients with vegetations, abscesses, and pseudoaneurysms are demonstrated in Figures 1 to 3 and Online Videos 1 and 2. Table 4 shows the prevalence of coronary artery disease and valvular disease, including quantitative measurements by CT. Discussion Pre-operative assessment of coronary artery disease with conventional coronary angiography has been recommended in the guidelines of the American College of Cardiology/ Figure 2 Bioprosthetic Valve Infective Endocarditis with Giant Pseudoaneurysm Multislice computed tomography (CT) (A to D) was superior to transesophageal echocardiography (TEE) (E) for showing the full extent and anatomic relationships of the aortic root pseudoaneurysm (A), such as its posterior extent (A, C, D) with impression of the left atrium (LA) and left pulmonary vein (D) and its close contact with the right coronary artery (RCA) (B) and left coronary artery (LCA) (D). Thickened leaflets were visualized with CT (D) and TEE (E) (white arrow). Prolapse of the anterior cusp (C, sagittal oblique view) during diastole caused severe regurgitation (black arrow) (Online Video 2). Calcifications of the stentless tissue valve indicated chronic inflammatory process (D). American Heart Association for selected patients scheduled for cardiac valve surgery (15). Recently introduced multislice CT allows noninvasive coronary artery imaging and has been shown to reliably exclude significant coronary artery

7 442 Feuchtner et al. JACC Vol. 53, No. 5, 2009 Multislice CT in Infective Endocarditis February 3, 2009: Figure 3 Mitral Valve and Left Atrial Vegetations Multislice CT image shows 3 mitral valve vegetations (A, black arrows; short-axis view) confirmed by TEE (B, white arrows). Left atrial vegetation (C by CT [left black arrow], and D by TEE [white arrow]). Right black arrow in C points to the thickened posterior mitral valve leaflet. stenosis (8,9). The major advantage of multislice CT over conventional coronary angiography in patients with acute IE is its noninvasiveness and thus avoidance of the high embolization risk of valvular vegetations during catheter manipulation. Once spread into the systemic arterial circulation, those vegetations can cause severe complications such as cerebral or peripheral embolization (17). In this study, multislice CT showed an excellent diagnostic performance in assessing morphologic abnormalities commonly seen in patients with IE. Accuracy of vegetation, abscess, and pseudoaneurysm detection with CT was similar to that of the clinical reference standard imaging modality, TEE. Size measurements of vegetations with CT showed a good concordance with TEE, and 4-dimensional cinemode allowed assessment of the mobility of vegetations, both of which represent risk factors for systemic arterial emboli (17 19). CT missed some small vegetations ( 4 mm), which may be attributed to the limited temporal resolution of multislice CT. Moreover, false positive findings occurred with CT (e.g., by misclassifying a degenerative lesion). However, CT correctly detected vegetations attached to a mechanic prosthetic valve that were missed by TEE. A similar experience has been recently reported (20) for a pannus causing mechanic prosthetic valve dysfunction. Moreover, multislice CT was helpful in distinguishing between calcified degenerative lesions and vegetations. All 4 mitral valve leaflet perforations ( 2 mm) were missed with CT, most probably related to lack of flow information that facilitates visualization of perforations with TEE. CT correctly detected paravalvular abscesses and pseudoaneurysms in all patients, whereas TEE missed 1. Perivalvular abscesses develop in up to 30% of patients with IE (21), and visualization with TTE is often difficult, leading to delayed diagnosis (22). The early detection of perivalvular abscesses is crucial because the mortality of patients increases up to 2-fold (22). Sensitivity for the detection of abscesses associated with IE has been reported to be only 28% for TTE and 87% for TEE (22). In our study, multislice CT provided better anatomic information than TEE with regards to the perivalvular extent such as myocardial, pericardial, and coronary sinus involvement, which was helpful for planning surgery (e.g., to avoid unsuccessful attempts of retrograde cannulation of the coronary sinus). Additionally, 3-dimensional visualization of periannular tissue destruction and the extent and ana-

8 JACC Vol. 53, No. 5, 2009 February 3, 2009: Feuchtner et al. Multislice CT in Infective Endocarditis 443 Prevalence of CAD in All Patients and Valvular Stenosis/Insufficiency in Patients Who Underwent Surgery Table 4 Prevalence of CAD in All Patients and Valvular Stenosis/Insufficiency in Patients Who Underwent Surgery (n 36)* No CAD <50% Stenosis >50% Stenosis Per-patient based analysis No. of patients 15/36 (42%) 17/36 (47%) 4/36 (11%) Single vessel (n) 12 3 Double vessel (n) 2 0 Triple vessel (n) 3 1 Per-artery based analysis LM 2 0 LAD 11 4 CX 7 1 RCA 5 2 (n 29) Severity by TEE Prevalence Regurgitant or Stenotic Orifice Area by CT Aortic regurgitation 10/29 (34%) Severe cm 2 Moderate cm 2 Mild 4 Mean 0.08 cm 2 in 2 patients; not detectable in 2 patients Aortic stenosis 2/29 (7%) Severe cm 2 Mitral regurgitation 9/29 (31%) Severe cm 2 Moderate cm 2 Mild 4 Not detected by CT in all 4 patients Mitral stenosis 1/29 (3%) Severe 1 *36 of 37 patients had previously unknown coronary artery disease (CAD). One patient had a single aortocoronary vein graft to CX, and evaluation of graft patency was clinically indicated. These patients underwent simultaneous coronary bypass grafting based on CT findings without invasive angiography. The grafting of the RCA in 1 patient with 3-vessel disease was unsuccessful because of paravalvular abscess/pseudoaneurysm, but the other 2 grafts were connected successfully. 2 patients had mild aortic regurgitation, and CT did not show a regurgitation orifice area (1 patient had severe calcifications [9512 Agatston score], and 1 patient had a bicuspid aortic valve). Mitral stenosis appeared after mitral valve annuloplasty; therefore, accurate quantification of the orifice area was not possible because of metal artifacts. CX circumflex artery; LAD left anterior descending artery; LM left main; RCA right coronary artery; other abbreviations as in Table 1. tomic relationships of a perivalvular pseudoaneurysm was helpful for pre-surgical planning (e.g., to anticipate the anastomotic site of a bypass graft, avoid injury of the circumflex artery in cases of paravalvular mitral valve abscess during abscess debridement, and predict the risk of a ventriculoatrial disconnection [ hole-in-one ]). Study limitations. The use of iodinated contrast media is contraindicated in patients with pre-existing renal dysfunction. Another limitation of multislice CT is the radiation exposure ranging from 9 to 11 msv for 64-slice CT (23) and 7 to 9 msv(24) for dual-source CT when echocardiogram pulsing for radiation dose reduction is used. However, cardiac CT allows comprehensive noninvasive assessment of coronary artery disease, and invasive coronary angiography can be avoided. Given the high mortality and morbidity of patients with acute IE, radiation exposure may be less concerning. Absolute arrhythmia such as atrial fibrillation represents a limitation of echocardiogram-gated multislice CT, leading to misalignment artifacts. However, high-temporal resolution dual-source CT may be considered in patients with normofrequent atrial fibrillation. Cardiac CT usually is aimed at visualizing the coronary arteries, including the left atrium, left ventricle, and mitral and aortic valves. Hence, valvular abnormalities associated with IE involving the pulmonary and tricuspid valves require an adaptation of the contrast media protocol (14) to achieve both left and right ventricular enhancement. Furthermore, the statistical power of the per-patient based analysis to exclude IE is limited because of low patient number. However, the per-valve based analysis included a high number of negative valves. Further prospective studies on consecutive patients with possible IE would be desirable to determine the accuracy of CT to rule out IE in patients with clinical suspicion but negative TEE. Conclusions Results from this preliminary study show a good diagnostic value of multislice CT for the detection of valvular abnormalities associated with IE. Vegetations, abscesses, and pseudoaneurysms were detected with a similar accuracy with CT compared with TEE. CT could be used as an alternative imaging tool in patients with clinical suspicion of IE after an initial negative or inconclusive TEE. In detail, these could be patients in whom a chest CT scan is clinically indicated because of fever of unknown origin in the presence of other pre-disposing factors for IE (3 minor criteria) or a positive hemoculture (1 major). CT might be also helpful if metallic artifacts hamper the visualization of prosthetic valves by TEE.

9 444 Feuchtner et al. JACC Vol. 53, No. 5, 2009 Multislice CT in Infective Endocarditis February 3, 2009: CT can be applied in clinical practice for the preoperative ruling out of coronary artery disease instead of invasive angiography, if indicated (e.g., because of coexistent aortic stenosis or clinically suspected coronary artery disease). Moreover, comprehensive evaluation of anatomic relationships of perivalvular abscess/pseudoaneurysms may be beneficial for pre-surgical planning. Reprint requests and correspondence: Dr. Gudrun M. Feuchtner, Innsbruck Medical University, Department of Radiology II, Anichstrasse 35, A-6020 Innsbruck, Austria. gudrun. REFERENCES 1. Bashore TM, Cabell C, Fowler V Jr., et al. Update on infective endocarditis. Curr Probl Cardiol 2006;31: Haldar S, O Gara T. Infective endocarditis: diagnosis and management. Nat Clin Pract Cardiovasc Med 2006;3: Durack DT, Lukes AS, Bright DK, et al. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994;96: Sachev M, Peterson G, Jollis G. Imaging techniques for diagnosis of infective endocarditis. Cardiol Clin 2003;21: 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 1988;9: Sochowski RA, Chan KL. Implication of negative results on a monoplane transesophageal echocardiographic study in patients with suspected infective endocarditis. J Am Coll Cardiol 1993;21: Vieira MLC, Grinberg M, Pomerantzeff PMA, Andrade JA, Mansur AJ. Repeated echocardiography examination of patients with suspected infective endocarditis. Heart 2004;90: Meijboom WB, Mollet NR, Van Mieghem CA, et al. Pre-operative computed tomography coronary angiography to detect significant coronary artery disease in patients referred for cardiac valve surgery. J Am Coll Cardiol 2006;48: Janne d Othée B, Siebert U, Cury R, Jadvar H, Dunn EJ, Hoffmann U. A systematic review on diagnostic accuracy of CT-based detection of significant coronary artery disease. Eur J Radiol 2008;65: Feuchtner GM, Dichtl W, Friedrich GJ, et al. Multislice computed tomography for detection of patients with aortic valve stenosis and quantification of severity. J Am Coll Cardiol 2006;47: Feuchtner GM, Dichtl W, Schachner T, et al. Diagnostic performance of MDCT for detecting aortic valve regurgitation. Am J Roentgenol 2006;186: Messika-Zeitoun D, Serfaty JM, Laissy JP, et al. Assessment of the mitral valve area in patients with mitral stenosis by multislice computed tomography. J Am Coll Cardiol 2006;48: Alkadhi H, Wildermuth S, Bettex DA, et al. Mitral regurgitation: quantification with 16-detector row CT-initial experience. Radiology 2006;238: Vrachliotis TG, Bis KG, Haidary A, et al. Atypical chest pain: coronary, aortic, and pulmonary vasculature enhancement at biphasic single-injection 64-section CT angiography. Radiology 2007;243: Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease). J Am Coll Cardiol 2006;48:e Cohen J. A coefficient for agreement of nominal scales. Educ Psychol Measure 1960;20: Vilacosta I, Graupner C, San Román JA, et al. Risk of embolization after institution of antibiotic therapy for infective endocarditis. J Am Coll Cardiol 2002;39: Di Salvo G, Habib G, Pergola V, et al. Echocardiography predicts embolic events in infective endocarditis. J Am Coll Cardiol 2001;37: Deprele C, Berthelot P, Lemetayer F, et al. Risk factors for systemic emboli in infective endocarditis. Clin Microbiol Infect 2004;10: Leborgne L, Renard C, Tribouilloy C. Usefulness of ECG-gated multi-detector computed tomography for the diagnosis of mechanical prosthetic valve dysfunction. Eur Heart J 2006;27: Rohmann S, Erbel R, Mohr-Kahaly S, Meyer J. Use of transoesophageal echocardiography in the diagnosis of abscess in infective endocarditis. Eur Heart J 1995;16 Suppl B: Daniel WG, Mugge A, Martin RP, et al. Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med 1991;324: Hausleiter J, Meyer T, Hadamitzky M, et al. Radiation dose estimates from cardiac multislice computed tomography in daily practice: impact of different scanning protocols on effective dose estimates. Circulation 2006;113: Stolzmann P, Scheffel H, Schertler T, et al. Radiation dose estimates in dual-source computed tomography coronary angiography. Eur Radiol 2008;18: Key Words: 64-slice computed tomography y CT y MSCT y valvular disease y infective endocarditis y cardiac surgery. APPENDIX For accompanying videos and legends, please see the online version of this article.