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Use of Echocardiography in Patients With Known or Suspected Infective Endocarditis
Cardiology Grand Rounds From The University of Texas Medical Branch
aortic valve leaflets (Figure 2). Five days later, the patient underwent aortic valve replacement utilizing a 23 mm St. Jude's aortic valve prosthesis. His postoperative course was unremarkable and he was discharged home to finish a 6-week course of antibiotic therapy.
Discussion
Editor
Marschall S. Runge, MD, PHD Coeditors
George A. Stouffer, MD Richard G. Sheahan, MD
Use of Echocardiography in Patients With Known or Suspected Infective Endocarditis Authors
Stamatios Lerakis, MD* Jonathan R. Lindner, MDt George A. Stouffer, MD*
Case Report A previously healthy 29-year-old man complained of generalized fatigue, malaise, and anorexia for approximately 1 month and left calf pain for 5 days. He had lost 20 pounds and reported markedly decreased exercise tolerance. The pain in his left leg had worsened progressively and occurred with exertion and at rest. He denied local trauma, fever, chills, or shortness of breath. He smoked tobacco on a regular basis but denied the use of alcohol or intravenous drugs. On physical examination, he was an ill-appearing young man. Blood pressure was 140/40, pulse 119 beats per minute, and temperature 38.5° C. Pertinent findings included a 2/6 holodiastolic murmur heard best along the left sternal border, a left ventricular lift, digital clubbing, and decreased left dorsalis pedis and posterior tibial pulses. His hematocrit was 19.3%, white blood cell count 14,800/mm3, and erythrocyte sedimentation rate 86 seconds. Electrocardiogram demonstrated sinus tachycardia with normal QRS complex duration. The patient was admitted to the hospital with suspected endocarditis, and intravenous gentamicin and penicillin were administered. Left lower extremity vascular studies were consistent with embolic occlusion and he was given intravenous heparin. Four sets of blood cultures were obtained; 72 hours later, gram-positive cocci in clusters (eventually identified as S viridans) were present in one culture. A transesophageal echocardiogram (TEE) was performed to decide optimal timing for valve replacement surgery. This test showed preserved left ventricular function, moderate to severe aortic insufficiency (Figure 1), and vegetations on all three
From the *Division of Cardiology, Department ofMedicine, University of Texas Medical Branch, Galveston, Texas, and the tCardiovascular Division, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia. Correspondence: George A. Stouffer, MD, Route 1064, Medical Research Building, 301 University Boulevard, University of Texas Medical Branch, Galveston, TX 77555-1064. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Microbial infection of the endocardium results in the clinical condition known as infective endocarditis (IE). This disease occurs in 2 to 4 people per 100,000 population and the incidence increases with age. Factors that predispose individuals to developing endocarditis include age, intravenous drug use, presence of prosthetic heart valve, and cardiac structural abnormalities. In industrialized countries, 65% to 75% of cases of native valve endocarditis occur in patients with abnormal valves from previous IE, myxomatous degeneration, congenital abnormalities (particularly bicuspid aortic valve), mitral valve prolapse (especially with mitral regurgitation and valve thickening), or rheumatic disease. Other structural abnormalities that can predispose an individual to IE include patent ductus arteriosus, ventricular septal defect, or hypertrophic cardiomyopathy. Predisposing factors are not identified in 25% to 45% of patients with IE. A provocative event (eg, dental procedure or intravenous drug use) causing bacteremia can be identified in approximately one half of the cases. 1 The microbiology ofIE changes with age, underlying health, use of intravenous drugs, and presence of a prosthetic valve. In patients with native valve infection who are not intravenous drug users, streptococci remain the most common infecting microorganisms, and among the streptococci, those of the viridans group are the most prevalent. Over time, there has been a reduction in the percentage of cases caused by viridans streptococci and an increase in cases caused by staphylococci and enterococci. This is thought to be due to the decrease in the prevalence of rheumatic heart disease over the past several decades. Currently, viridans streptococci, staphylococci, enterococci, and aerobic gram-negative bacilli account for more than 95% of episodes of native valve endocarditis. In intravenous drug users, S aureus is the most common organism, accounting for approximately 60% of cases (and approximately 80% of cases of tricuspid or pulmonic endocarditis). Prosthetic valve endocarditis (PVE) has a different microbiology spectrum depending on whether it occurs "early" (within 1 year) or "late": coagulase-negative staphylococcus is the most common organism isolated in early PVE, but streptococcus is the most common organism isolated in late PVE. 1 The diagnosis of endocarditis remains a major clinical challenge. Many of the symptoms associated with IE, such as fever, chills, sweats, anorexia, malaise, and dyspnea, occur in a variety of disease states. Furthermore, patients may present with symptoms caused by embolic phenomenon, as in the patient described here. The "classic" physical examination findings associated with IE, such as Janeway
209
Cardiology Grand Rounds From The University of Texas Medical Branch
Figure 1. Color flow Doppler image from transesophageal echocardiogram (long axis view) demonstrating turbulent, regurgitant flow from aorta to left ventricle.
lesions, Roth spots, Osler nodes or splinter hemorrhages, are generally seen in less than 15% of patients. The best evidence for the diagnosis of IE remains isolation of an infectious organism from the blood stream of an individual with a new or changing cardiac murmur, with the only gold standard being pathologic confirmation at surgery or autopsy. The use of echocardiography has had a major impact on the diagnosis and treatment of endocarditis. When combined with clinical findings, echocardiography can provide very important information supporting or refuting the diagnosis of IE. Findings on echocardiography that are indicative of endocardial infection include:
1. an oscillating intracardiac mass (ie, vegetation on a valve, supporting structure, or implante, material, or in the path of a regurgitant jet; 2. an abscess; 3. new partial dehiscence of prosthetic valve; or 4. new or worsening valvular regurgitation. In addition to its value in diagnosis, echocardio~ raphy provides valuable information regarding con plications associated with endocarditis, prognosi~ and response to treatment. Detection of IE by Echocardiography. Vegetation were first identified on M-mode echocardiography a shaggy echoes with nonuniform thickening assoc ated with valves that exhibited normal motion. 2 Th development of two-dimensional echocardiograph permitted assessment of the size, motion, and loc~ tion of vegetative lesions in addition to increasin the accuracy of detection. 3 ,4 Sensitivity of detectin evidence of IE has been further enhanced with th addition of TEE , which allows more thorough inspe~ tion of cardiac structures and is less subject to in aging artifacts. In patients with endocarditis cOl firmed by surgery or at autopsy, sensitivity of TE is approximately 90%, while the sensitivity oftran! thoracic echocardiography (TTE) is approximate] 50%.5 TEE can detect vegetation as small as 2 ml in size, while TTE cannot detect vegetations small( than 5 mm. Assessment of prosthetic valves by echocardiogrl phy is more difficult than assessment of nath valves due to the potential artifacts caused by tr highly reflective nature of prosthetic valve materia On average, the sensitivity of TTE for detecting vegetation on a prosthetic rather than a native vah is reduced by about half. 6 - s For example, Daniell al 9 in a series of 126 consecutive patients with 14
Figure 2. Two-dimensional images from transesophageal echocardiogram demonstrating vegetations on the aortic valve in short (A) and long axis (B) views. LA = left atrium; LV = left ventricle; veg = vegetation.
210
aJ
September 1998 Volume 316 Numbe
Lerakis, Lindner, and Stouffer
prosthetic valves (113 bioprostheses and 35 mechanical) compared TTE and TEE for detecting valve endocarditis. Detection of vegetations was significantly enhanced by the use of TEE compared to TTE (82 vs. 36%, P < .001). Similarly, Daniel and Mugge 10 in their series found that TTE detected 58% of vegetations, but TEE was able to detect 90%. Apart from detecting valvular vegetations, echocardiography is also useful for identifying the presence of intramyocardial abscesses, which are diagnosed at surgery or by autopsy in up to 30% of cases of IE. The presence of an abscess is usually associated with a more severe course of the disease. TEE has been shown to be much more sensitive in the detection of abscesses than TTE, largely due to higher transducer frequencies and less interference from chest wall structures and lung. Daniel et al l l prospectively studied 118 patients and found that TEE had a sensitivity for detecting surgically or autopsy-confirmed abscesses of 87% compared to 28% with TTE. Specificity was equal with the two modalities. Involvement of subaortic structures such as the mitral-aortic intervalvular fibrosa (MAIVF) and the basal portion ofthe arterior mitral leaflet (AML) can occur in patients with aortic valve endocarditis. The secondary involvement of these structures occurs as a result of direct extension of the infection from the aortic valves or as a result of an aortic regurgitant jet striking the ventricular surfaces of the MAIVF or anterior mitral leaflet (AML). Karalis et aF 2 examined the usefulness of echocardiography in the detection of subaortic complications in 55 consecutive patients with aortic valve endocarditis. As determined by TEE, 24 patients had involvement of subaortic structures. TEE findings were confirmed at surgery in 20 of these patients, and at autopsy in2 patients. TTE was much less sensitive, identifying subaortic pathology in only 5 patients and an eccentric mitral regurgitation jet (suspicious for, but not diagnostic of, subaortic pathology) in an additional 8 patients. Factors That Influence Studies Evaluating the Performance of Echocardiography in Suspected IE. A sig-
nificant obstacle in determining the performance of echocardiography in IE is the lack of a gold standard for diagnosis. Few studies evaluating the role of echocardiography include only patients in which IE was confirmed by pathologic identification of infected endocardium. There is a higher incidence of echocardiographically evident vegetations in patients with more severe disease, and thus the "performance" of echo cardiography will be influenced by the criteria used to enroll patients. In select cohorts of patients identified by strict clinical criteria such as new fever, new murmur, and bacteremia, the sensitivity of even M-mode echocardiography has been reported as high as 75% to 78%.4 If "less stringent" THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
clinical criteria are used, the performance of echo cardiography will be lower than when strict clinical or autopsy criteria are employed. 6,7,13 Advantages of using less stringent clinical variables to identify patients for study are a larger population and a more realistic representation of common clinical practice. The disadvantage is the possible inclusion of patients without endocardial infection. The reported performance of echocardiography in IE may also be influenced by varying definitions of positive test results. A vegetation can be defined, for instance, as a mass with different acoustic characteristics and motion independent of other cardiac structures, or merely as diffuse valve thickening. If a positive echo cardiographic study is defined by very specific criteria, the diagnostic certainty will be increased at the expense of sensitivity. Conversely, a low threshold for defining a test as positive would yield less diagnostic certainty with higher sensitivity. Clinical Utility of the Test. In taking care of an individual patient, clinical findings and echocardiographic data provide complementary information to enable proper diagnosis. In order to determine the clinical usefulness of echocardiography, it is thus necessary to assess its additive diagnostic value. According to Bayesian theory, diagnostic echocardiography should be most valuable when other available information suggests a median probability of disease. To study this, Lindner et al 14 prospectively evaluated 105 consecutive patients with suspected endocarditis by both TTE and TEE. Patients were classified as having a low, medium, or high clinical probability of IE based on well-defined criteria that did not incorporate echocardiographic findings. Echocardiograms were evaluated by readers who were blinded to the clinical information and who categorized the studies as indicating high, intermediate, or low probability of endocarditis based on well-defined criteria. Of the 67 patients with low clinical probability of endocarditis, TTE and TEE classified the majority (82% and 85%, respectively) as having a low likelihood of the disease. Of the 14 patients with intermediate clinical probability, additional positive or negative information was provided in all patients by TEE and in most patients by TTE. Interestingly, many of the 24 patients with high clinical probability were placed in the low likelihood category by echocardiography (15 by TTE and 12 by TEE). This finding might by explained by the difficulty in discriminating between medium and high clinical probability when nonspecific physical examination findings were included. Echocardiography may also be useful in determining prognosis. Multiple studies have demonstrated that the presence of vegetations as determined by echocardiography is a predictor of higher rates of complications,5,15,16 although there is still contro-
211
Cardiology Grand Rounds From The University of Texas Medical Branch
versy about whether vegetation size is predictive of embolic events and other complications. 6 ,17 More studies are needed to determine in which patients the information obtained from echocardiography improves outcome and decreases complications.
5.
6.
Summary
Ultrasonographic examination enables the detection of vegetations, valvular regurgitation, intramyocardial abscesses, and sub aortic complications in patients with suspected endocarditis, but the role echocardiography should play in the diagnosis and management of patients with suspected IE is still somewhat unclear. Echocardiography is useful when the clinical suspicion of IE is intermediate or high but of little value in individuals in whom the suspicion is low. In patients with known endocarditis, echocardiography may provide information important to optimal management. TEE is generally superior to TTE, especially in patients with prosthetic valves, in the detection of abscess formation, and in those patients in whom TTE is either inadequate or indicates an intermediate probability of endocarditis. Despite recent advances in our understanding of the role echocardiography should play in patients with known or suspected IE, there remain many unanswered questions and it should be emphasized that echocardiographic data must be interpreted in conjunction with clinical information.
7.
8.
9.
10. 11.
12.
13.
References 1. Karchmer AW. Infective Endocarditis. In: Braunwald E, ed. Heart Disease. 5th ed. Philadelphia: WB Saunders; 1997: 1077-1104. 2. Dillon JC, Feigenbaum H, Konecke LL, Davis RH, Chang S. Echocardiographic manifestations ofvalvularvegetations. Am Heart J. 1973;86:698-704. 3. Lutas EM, Roberts RB, Devereux RB, Prieto LM. Relation between the presence of echocardiographic vegetations and the complication rate in infective endocarditis. Am Heart J.1986;112:107-13. 4. Wann LS, Hallam CC, Dillon JC, Weyman AE, Feigenbaum H. Comparison ofM-mode and cross-sectional echocar-
212
14. 15. 16. 17.
diography in infective endocarditis. Circulation. 1979; 60:728-33. Pedersen WR, Walker M, Olson JD, Gobel F, Lange HW, Daniel JA, et al. Value of transesophageal echocardiographyas an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. Chest. 1991; 100:351-6. Mugge A, Daniel WG, Frank G, Lichtlen PRo Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am ColI Cardiol. 1989; 14:631-8. Shively BK, Gurule FT, Roldan CA, Leggett JH, Schiller NB. Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis. J Am ColI Cardiol. 1991; 18:391-7. Lowry RW, Zoghbi WA, Baker WB, Wray RA, Quinones MA. Clinical impact of transesophageal echocardiography in the diagnosis and management of infective endocarditis. Am J Cardiol. 1994;73:1089-91. Daniel WG, Mugge A, Grote J, Hausmann D, Nikutta P, Laas 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. 1993; 71:210-5. Daniel WG, Mugge A. Transesophageal echocardiography. N Engl J Med. 1995;332:1268-79. Daniel WG, Mugge A, Martin RP, Lindert 0, Hausmann D, Nonnast-Daniel B, et al. Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med. 1991;324:795-800. Karalis DG, Bansal RC, Hauck AJ, Ross JJ Jr, Applegate PM, Jutzy KR, et aI. Transesophageal echocardiographic recognition of subaortic complications in aortic valve endocarditis. Circulation. 1992;86:353-62. Sanfilippo AJ, Picard MH, Newell JB, Rosas E, Davidoff R, Thomas JD, Weyman AE. Echocardiographic assessment of patients with infectious endocarditis: prediction of risk for complications. J Am ColI Cardiol. 1991; 18:1191-9. Lindner JR, Case RA, Dent JM, Abbott RD, Scheid WM, Kaul S. Diagnostic value of echocardiography in suspected endocarditis. Circulation. 1996;93:730-6. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med. 1994; 96:200-9. Wann LS, Dillon JC, Weyman AE, Feigenbaum H. Echocardiography in bacterial endocarditis. N Engl J Med. 1976;295:135-9. Robbins MJ, Frater RW, Soeiro R, Frishman WH, Strom JA. Influence of vegetation size on clinical outcome of rightsided infective endocarditis. Am J Med. 1986;80:165-71.
September 1998 Volume 316 Number 3
aortic valve leaflets (Figure 2). Five days later, the patient underwent aortic valve replacement utilizing a 23 mm St. Jude's aortic valve prosthesis. His postoperative course was unremarkable and he was discharged home to finish a 6-week course of antibiotic therapy.
Discussion
Editor
Marschall S. Runge, MD, PHD Coeditors
George A. Stouffer, MD Richard G. Sheahan, MD
Use of Echocardiography in Patients With Known or Suspected Infective Endocarditis Authors
Stamatios Lerakis, MD* Jonathan R. Lindner, MDt George A. Stouffer, MD*
Case Report A previously healthy 29-year-old man complained of generalized fatigue, malaise, and anorexia for approximately 1 month and left calf pain for 5 days. He had lost 20 pounds and reported markedly decreased exercise tolerance. The pain in his left leg had worsened progressively and occurred with exertion and at rest. He denied local trauma, fever, chills, or shortness of breath. He smoked tobacco on a regular basis but denied the use of alcohol or intravenous drugs. On physical examination, he was an ill-appearing young man. Blood pressure was 140/40, pulse 119 beats per minute, and temperature 38.5° C. Pertinent findings included a 2/6 holodiastolic murmur heard best along the left sternal border, a left ventricular lift, digital clubbing, and decreased left dorsalis pedis and posterior tibial pulses. His hematocrit was 19.3%, white blood cell count 14,800/mm3, and erythrocyte sedimentation rate 86 seconds. Electrocardiogram demonstrated sinus tachycardia with normal QRS complex duration. The patient was admitted to the hospital with suspected endocarditis, and intravenous gentamicin and penicillin were administered. Left lower extremity vascular studies were consistent with embolic occlusion and he was given intravenous heparin. Four sets of blood cultures were obtained; 72 hours later, gram-positive cocci in clusters (eventually identified as S viridans) were present in one culture. A transesophageal echocardiogram (TEE) was performed to decide optimal timing for valve replacement surgery. This test showed preserved left ventricular function, moderate to severe aortic insufficiency (Figure 1), and vegetations on all three
From the *Division of Cardiology, Department ofMedicine, University of Texas Medical Branch, Galveston, Texas, and the tCardiovascular Division, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia. Correspondence: George A. Stouffer, MD, Route 1064, Medical Research Building, 301 University Boulevard, University of Texas Medical Branch, Galveston, TX 77555-1064. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Microbial infection of the endocardium results in the clinical condition known as infective endocarditis (IE). This disease occurs in 2 to 4 people per 100,000 population and the incidence increases with age. Factors that predispose individuals to developing endocarditis include age, intravenous drug use, presence of prosthetic heart valve, and cardiac structural abnormalities. In industrialized countries, 65% to 75% of cases of native valve endocarditis occur in patients with abnormal valves from previous IE, myxomatous degeneration, congenital abnormalities (particularly bicuspid aortic valve), mitral valve prolapse (especially with mitral regurgitation and valve thickening), or rheumatic disease. Other structural abnormalities that can predispose an individual to IE include patent ductus arteriosus, ventricular septal defect, or hypertrophic cardiomyopathy. Predisposing factors are not identified in 25% to 45% of patients with IE. A provocative event (eg, dental procedure or intravenous drug use) causing bacteremia can be identified in approximately one half of the cases. 1 The microbiology ofIE changes with age, underlying health, use of intravenous drugs, and presence of a prosthetic valve. In patients with native valve infection who are not intravenous drug users, streptococci remain the most common infecting microorganisms, and among the streptococci, those of the viridans group are the most prevalent. Over time, there has been a reduction in the percentage of cases caused by viridans streptococci and an increase in cases caused by staphylococci and enterococci. This is thought to be due to the decrease in the prevalence of rheumatic heart disease over the past several decades. Currently, viridans streptococci, staphylococci, enterococci, and aerobic gram-negative bacilli account for more than 95% of episodes of native valve endocarditis. In intravenous drug users, S aureus is the most common organism, accounting for approximately 60% of cases (and approximately 80% of cases of tricuspid or pulmonic endocarditis). Prosthetic valve endocarditis (PVE) has a different microbiology spectrum depending on whether it occurs "early" (within 1 year) or "late": coagulase-negative staphylococcus is the most common organism isolated in early PVE, but streptococcus is the most common organism isolated in late PVE. 1 The diagnosis of endocarditis remains a major clinical challenge. Many of the symptoms associated with IE, such as fever, chills, sweats, anorexia, malaise, and dyspnea, occur in a variety of disease states. Furthermore, patients may present with symptoms caused by embolic phenomenon, as in the patient described here. The "classic" physical examination findings associated with IE, such as Janeway
209
Cardiology Grand Rounds From The University of Texas Medical Branch
Figure 1. Color flow Doppler image from transesophageal echocardiogram (long axis view) demonstrating turbulent, regurgitant flow from aorta to left ventricle.
lesions, Roth spots, Osler nodes or splinter hemorrhages, are generally seen in less than 15% of patients. The best evidence for the diagnosis of IE remains isolation of an infectious organism from the blood stream of an individual with a new or changing cardiac murmur, with the only gold standard being pathologic confirmation at surgery or autopsy. The use of echocardiography has had a major impact on the diagnosis and treatment of endocarditis. When combined with clinical findings, echocardiography can provide very important information supporting or refuting the diagnosis of IE. Findings on echocardiography that are indicative of endocardial infection include:
1. an oscillating intracardiac mass (ie, vegetation on a valve, supporting structure, or implante, material, or in the path of a regurgitant jet; 2. an abscess; 3. new partial dehiscence of prosthetic valve; or 4. new or worsening valvular regurgitation. In addition to its value in diagnosis, echocardio~ raphy provides valuable information regarding con plications associated with endocarditis, prognosi~ and response to treatment. Detection of IE by Echocardiography. Vegetation were first identified on M-mode echocardiography a shaggy echoes with nonuniform thickening assoc ated with valves that exhibited normal motion. 2 Th development of two-dimensional echocardiograph permitted assessment of the size, motion, and loc~ tion of vegetative lesions in addition to increasin the accuracy of detection. 3 ,4 Sensitivity of detectin evidence of IE has been further enhanced with th addition of TEE , which allows more thorough inspe~ tion of cardiac structures and is less subject to in aging artifacts. In patients with endocarditis cOl firmed by surgery or at autopsy, sensitivity of TE is approximately 90%, while the sensitivity oftran! thoracic echocardiography (TTE) is approximate] 50%.5 TEE can detect vegetation as small as 2 ml in size, while TTE cannot detect vegetations small( than 5 mm. Assessment of prosthetic valves by echocardiogrl phy is more difficult than assessment of nath valves due to the potential artifacts caused by tr highly reflective nature of prosthetic valve materia On average, the sensitivity of TTE for detecting vegetation on a prosthetic rather than a native vah is reduced by about half. 6 - s For example, Daniell al 9 in a series of 126 consecutive patients with 14
Figure 2. Two-dimensional images from transesophageal echocardiogram demonstrating vegetations on the aortic valve in short (A) and long axis (B) views. LA = left atrium; LV = left ventricle; veg = vegetation.
210
aJ
September 1998 Volume 316 Numbe
Lerakis, Lindner, and Stouffer
prosthetic valves (113 bioprostheses and 35 mechanical) compared TTE and TEE for detecting valve endocarditis. Detection of vegetations was significantly enhanced by the use of TEE compared to TTE (82 vs. 36%, P < .001). Similarly, Daniel and Mugge 10 in their series found that TTE detected 58% of vegetations, but TEE was able to detect 90%. Apart from detecting valvular vegetations, echocardiography is also useful for identifying the presence of intramyocardial abscesses, which are diagnosed at surgery or by autopsy in up to 30% of cases of IE. The presence of an abscess is usually associated with a more severe course of the disease. TEE has been shown to be much more sensitive in the detection of abscesses than TTE, largely due to higher transducer frequencies and less interference from chest wall structures and lung. Daniel et al l l prospectively studied 118 patients and found that TEE had a sensitivity for detecting surgically or autopsy-confirmed abscesses of 87% compared to 28% with TTE. Specificity was equal with the two modalities. Involvement of subaortic structures such as the mitral-aortic intervalvular fibrosa (MAIVF) and the basal portion ofthe arterior mitral leaflet (AML) can occur in patients with aortic valve endocarditis. The secondary involvement of these structures occurs as a result of direct extension of the infection from the aortic valves or as a result of an aortic regurgitant jet striking the ventricular surfaces of the MAIVF or anterior mitral leaflet (AML). Karalis et aF 2 examined the usefulness of echocardiography in the detection of subaortic complications in 55 consecutive patients with aortic valve endocarditis. As determined by TEE, 24 patients had involvement of subaortic structures. TEE findings were confirmed at surgery in 20 of these patients, and at autopsy in2 patients. TTE was much less sensitive, identifying subaortic pathology in only 5 patients and an eccentric mitral regurgitation jet (suspicious for, but not diagnostic of, subaortic pathology) in an additional 8 patients. Factors That Influence Studies Evaluating the Performance of Echocardiography in Suspected IE. A sig-
nificant obstacle in determining the performance of echocardiography in IE is the lack of a gold standard for diagnosis. Few studies evaluating the role of echocardiography include only patients in which IE was confirmed by pathologic identification of infected endocardium. There is a higher incidence of echocardiographically evident vegetations in patients with more severe disease, and thus the "performance" of echo cardiography will be influenced by the criteria used to enroll patients. In select cohorts of patients identified by strict clinical criteria such as new fever, new murmur, and bacteremia, the sensitivity of even M-mode echocardiography has been reported as high as 75% to 78%.4 If "less stringent" THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
clinical criteria are used, the performance of echo cardiography will be lower than when strict clinical or autopsy criteria are employed. 6,7,13 Advantages of using less stringent clinical variables to identify patients for study are a larger population and a more realistic representation of common clinical practice. The disadvantage is the possible inclusion of patients without endocardial infection. The reported performance of echocardiography in IE may also be influenced by varying definitions of positive test results. A vegetation can be defined, for instance, as a mass with different acoustic characteristics and motion independent of other cardiac structures, or merely as diffuse valve thickening. If a positive echo cardiographic study is defined by very specific criteria, the diagnostic certainty will be increased at the expense of sensitivity. Conversely, a low threshold for defining a test as positive would yield less diagnostic certainty with higher sensitivity. Clinical Utility of the Test. In taking care of an individual patient, clinical findings and echocardiographic data provide complementary information to enable proper diagnosis. In order to determine the clinical usefulness of echocardiography, it is thus necessary to assess its additive diagnostic value. According to Bayesian theory, diagnostic echocardiography should be most valuable when other available information suggests a median probability of disease. To study this, Lindner et al 14 prospectively evaluated 105 consecutive patients with suspected endocarditis by both TTE and TEE. Patients were classified as having a low, medium, or high clinical probability of IE based on well-defined criteria that did not incorporate echocardiographic findings. Echocardiograms were evaluated by readers who were blinded to the clinical information and who categorized the studies as indicating high, intermediate, or low probability of endocarditis based on well-defined criteria. Of the 67 patients with low clinical probability of endocarditis, TTE and TEE classified the majority (82% and 85%, respectively) as having a low likelihood of the disease. Of the 14 patients with intermediate clinical probability, additional positive or negative information was provided in all patients by TEE and in most patients by TTE. Interestingly, many of the 24 patients with high clinical probability were placed in the low likelihood category by echocardiography (15 by TTE and 12 by TEE). This finding might by explained by the difficulty in discriminating between medium and high clinical probability when nonspecific physical examination findings were included. Echocardiography may also be useful in determining prognosis. Multiple studies have demonstrated that the presence of vegetations as determined by echocardiography is a predictor of higher rates of complications,5,15,16 although there is still contro-
211
Cardiology Grand Rounds From The University of Texas Medical Branch
versy about whether vegetation size is predictive of embolic events and other complications. 6 ,17 More studies are needed to determine in which patients the information obtained from echocardiography improves outcome and decreases complications.
5.
6.
Summary
Ultrasonographic examination enables the detection of vegetations, valvular regurgitation, intramyocardial abscesses, and sub aortic complications in patients with suspected endocarditis, but the role echocardiography should play in the diagnosis and management of patients with suspected IE is still somewhat unclear. Echocardiography is useful when the clinical suspicion of IE is intermediate or high but of little value in individuals in whom the suspicion is low. In patients with known endocarditis, echocardiography may provide information important to optimal management. TEE is generally superior to TTE, especially in patients with prosthetic valves, in the detection of abscess formation, and in those patients in whom TTE is either inadequate or indicates an intermediate probability of endocarditis. Despite recent advances in our understanding of the role echocardiography should play in patients with known or suspected IE, there remain many unanswered questions and it should be emphasized that echocardiographic data must be interpreted in conjunction with clinical information.
7.
8.
9.
10. 11.
12.
13.
References 1. Karchmer AW. Infective Endocarditis. In: Braunwald E, ed. Heart Disease. 5th ed. Philadelphia: WB Saunders; 1997: 1077-1104. 2. Dillon JC, Feigenbaum H, Konecke LL, Davis RH, Chang S. Echocardiographic manifestations ofvalvularvegetations. Am Heart J. 1973;86:698-704. 3. Lutas EM, Roberts RB, Devereux RB, Prieto LM. Relation between the presence of echocardiographic vegetations and the complication rate in infective endocarditis. Am Heart J.1986;112:107-13. 4. Wann LS, Hallam CC, Dillon JC, Weyman AE, Feigenbaum H. Comparison ofM-mode and cross-sectional echocar-
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14. 15. 16. 17.
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September 1998 Volume 316 Number 3