Infective Endocarditis: A Challenging Disease

Update on Diagnostic Techniques

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Infective Endocarditis: A Challenging Disease Charles Z. Naggar, M.D.,* and Pierre Forgacs, M.D.t

Infective endocarditis is best characterized as a disease in evolution. Its varying modes of presentation and its wide range of serious complications continue to challenge the physician with difficult diagnostic and therapeutic problems. With each passing decade, the list of patients at risk for the development of infective endocarditis, which formerly contained largely patients with rheumatic heart disease, is modified and expanded. Currently, patients with prosthetic cardiac valves, users of illicit parenteral drugs, and patients with mitral valve prolapse rather than patients with rheumatic heart disease account for the majority of cases of infective endocarditis. The classic presentation of infective endocarditis is encountered less frequently. Increasingly, the complications of infective endocarditis rather than the infection itself pose the major therapeutic challenge. The availability of antimicrobial agents and the widespread use of echocardiography to visualize bacterial vegetations l5 . 33 in vivo along with improved surgical skills have favorably altered the natural history of infective endocarditis. The current literature contains numerous excellent and exhaustive treatises on the subject. 7. 8, 11, 13, 22, 2.3, 31,32, 34, 35. 37-41 This article details our recent experience with the clinical manifestations of infective endocarditis, highlighting the changing nature of this disease, emphasizing the role of echocardiography, and presenting recent therapeutic modalities.

Pathogenesis Defined as an intravascular infection, endocarditis results from colonization of the endothelium, cardiac as well as extracardiac, by microorgaWith the technical assistance of Maria Palma Seljan, M.D., and Debra A. Dumont, B.S., R.D.M.S. *Director, Noninvasive Laboratory, Section of Cardiology, Lahey Clinic Medical Center, Burlington, Massachusetts tHead, Section of Infectious Diseases, Lahey Clinic Medical Center, Burlington, Massachusetts

Medical Clinics of North America-Vo!' 70, No. 6, November 1986

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nisms. Usually, infective endocarditis refers to microbial, bacterial, or fungal infection within the heart. Some bacteria, such as Staphylococcus aureus, pneumococcus, beta-hemolytic streptococcus, and gonococcus, usually seed on normal cardiac valves from a primary source of infection elsewhere in the body. On the other hand, Staphylococcus epidermidis, diphtheroids, Streptococcus viridans, enterococcus, and gram-negative organisms cause infective endocarditis on previously damaged native valves, certain congenital cardiac deformities, prosthetic cardiac valves, or arteriovenous fistulas. Three hemodynamic factors predispose patients to the growth of infective vegetations: a high-velocity jet stream, flow from a high- to a lowpressure chamber, and a comparatively narrow orifice separating the two chambers that creates a pressure gradient. 25 These hemodynamic derangements are present in patients with aortic and mitral regurgitation, small interventricular septal defect, patent ductus arteriosus, and subaortic and valvular aortic stenosis, all of which are characteristic lesions predisposing patients to the development of infective endocarditis. Recently, Doppler echocardiography demonstrated inherent mild degrees of tricuspid and pulmonic insufficiencies in normal native valves, thus further explaining the right-sided predilection of infective endocarditis in drug abusers. The lesions of infective endocarditis tend to form just beyond the narrowed orifice through which the high-velocity jet stream passes-that is, on the ventricular surfaces of the semilunar valves, on the atrial surfaces of the atrioventricular valves, and on the walls of the pulmonary artery at the orifice of the patent ductus arteriosus. Satellite lesions of infective endocarditis can also grow where the jet stream strikes the endocardium-that is, the atrial wall opposite the mitral orifice in mitral regurgitation, the papillary muscle of the left ventricle in aortic regurgitation, and the surface of the pulmonary artery opposite the patent ductus arteriosus. The presumption is that the force of the jet stream against these sites injures the endothelium and creates foci uet lesions) that are susceptible to the growth of secondary infective vegetations. Because echocardiography can now visualize these vegetations in vivo, such anatomic localization of infective vegetations should be borne in mind. Bacteremia may follow surgical procedures (urethral instrumentation, curettage, incision of abscesses, gastrointestinal tract operation, or septorhinoplasty) or the use of contaminated hypodermic needles for parenteral applications, ear piercing, or acupuncture. lO Bacteremia is the principal insult that initiates the process of endocarditis, although in many patients with infective endocarditis no apparent portal of entry for bacteremia is identified.

Clinical Presentation The following five case histories highlight the myriad of presenting symptoms, the spectrum of clinical manifestations, and the complications encountered in patients with infective endocarditis. Case 1. Infective Endocarditis Masquerading as Recurrent Systemic Emboli. A 34-year-old man was known to have had a heart murmur since the age of 12. No past history of rheumatic fever was reported, however.

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Four years before, palpitations prompted cardiac evaluation, which documented mitral valve prolapse. No treatment was recommended. The past medical history was positive for migraine headaches. Ten weeks before admission, after dental extraction, the patient became febrile. Therapy with orally administered antibiotics was prescribed for 3 days. Six weeks before hospitalization, the patient complained of transient weakness in the left upper extremity and left facial numbness, which was attributed to the migraine headaches. Four weeks later, the patient complained of visual spots, and changes of retinal infarction were seen in the left fundus. One week before hospitalization, transient blanching of the left arm and left hand developed in association with paresthesias. No specific therapy was advised. Because of a loud systolic murmur, the patient was referred for cardiac evaluation. On physical examination, the patient had an oral temperature of 39.2°C (102.6°F), multiple conjunctival petechiae, and subungual splinter hemorrhages bilaterally, with mild clubbing of the fingers but no cyanosis. The patient had splenomegaly by palpation. A pansystolic murmur (grade IIIIVI) was heard over the precordium. The hemoglobin level was 12.7 g/dl, and the erythrocyte sedimentation rate was 58 mm/h by the Westergren method. Urinalysis showed microscopic hematuria. Blood cultures grew S. viridans. Echocardiography demonstrated three vegetations-the first on the atrial side of the anterior mitral leaflet, the second on the atrial side of the posterior mitral leaflet, and the third on the ventricular side of the right coronary cusp of the aortic valve (Fig. 1). Left ventricular and atrial dilation were consistent with hemodynamically severe mitral regurgitation. Electrocardiography indicated left ventricular hypertrophy (Fig. 2). A 4week course of antimicrobial therapy achieved bacteriologic cure. The ensuing hospital course was uneventful, and the patient was free of congestive heart failure and recurrent emboli. Serial echocardiography showed no change in the size of the vegetations.

Figure 1. Still frame of the parasternal echocardiographic view of the patient discussed in case 1 (left) and a schematic replica of the echocardiogram (right). This echocardiographic view is parallel to the long axis of the left ventricle and was recorded in late diastole. Stippled areas, vegetations on the anterior right c'oronary cusp of the aortic valve, the anterior mitral leaflet, and the posterior mitral leaflet. A = anterior. AML = anterior mitral leaflet. Ao = aortic root. I = inferior. IVS = interventricular septum. LA = left atrium. LV = left ventricle. N<;;C = noncoronary cusp of the aortic valve. P = posterior. PML = posterior mitral leaflet. RCC = right coronary cusp of the aortic valve. RV = right ventricle. S = superior. Veg. = vegetation.

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Figure 2. Resting electrocardiogram of patient discussed in case 1. Note the tall precordial voltage indicating left ventricular hypertrophy consistent with severe mitral regurgitation and the short PR interval with delta wave, indicating the presence of a WoHf-Parkinson-White syndrome.

Comment. The naggingly chronic course of infective endocarditis masquerading as recurrent systemic emboli is highlighted in this patient. We follow the guidelines for prophylactic antibiotic therapy recommended by the Committee on Rheumatic Fever and Infective Endocarditis of the Council on Cardiovascular Disease in the Young. 28 However, antibiotic therapy for infective endocarditis is usually 4 to 6 weeks. Case 2. Infective Endocarditis Presenting as Chronic Anemia and Recurrent Pulmonary Infiltrates. A previously healthy 29-year-old man with no history of rheumatic fever or drug abuse complained of fever and chills in February 1983, which were diagnosed as a viral illness. In March 1983, recurrent fever was treated with orally administered erythromycin for suspected acute bronchitis. In April 1983, chest radiography showed an infiltrate in the left lower lobe of the lung, prompting a second course of oral antibiotic therapy. At that time, a mild anemia was treated with an iron supplement. In May 1983, recurrent fever and cough were associated with a persistent consolidation in the left lower lobe of the lung as seen by chest radiography. The hemoglobin level was 10.8 gldl, erythrocyte sedimentation rate was 90 mm/h by the Westergren method, and bone marrow aspiration indicated anemia of chronic disease. In June 1983, recurrent fever and persistent anemia necessitated hospitalization. On physical examination a grade 1IIYI systolic murmur was heard over the right lower sternal border, which increased in intensity during inspiration. No subungual hemorrhages or conjunctival petechiae were evident. The white blood cell count was 14,300/mm 3 with a shift to the left, and the hematocrit value was 33%. Blood cultures grew Neisseria mucosa sensitive to penicillin at a minimal bactericidal concentration of 0.5 flglml. Echocardiographic findings showed a trilobed vegetation attached to the atrial side of the septal leaflet of the tricuspid valve (Fig. 3). Neither intrinsic valvular

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cm

Figure 3. An apical four-chamber echocardiographic view recorded in late diastole in the patient discussed in case 2. Note the lobulated vegetation attached to the atrial side of the septal leaflet of the tricuspid valve (stippled area). I = inferior. L = left. LA = left atrium. LV = left ventricle. R = right. RA = right atrium. RV = right ventricle. S = superior.

heart disease nor enlargement of the cardiac chamber was noted. Serial chest radiographs demonstrated recurrent infiltrates in the lower lobe of the lung (Fig. 4). Cultures of sputum grew normal flora. After 4 weeks of intravenously administered penicillin therapy, the patient improved and was discharged. In July 1983, the patient was readmitted with a relapse of endocarditis caused by N. mucosa. On dental examination, a periapical abscess was found. Intravenously administered penicillin and intramuscularly injected streptomycin achieved bacteriologic cure. The second hospitalization was marred by recurrent infiltrates in the chest associated with cough and pleuritic chest pain representing septic pulmonary emboli. Serial echocardiography demonstrated increase in size of the bacterial vegetation. The patient took Coumadin from September 1983 to June 1984 until echocardiography revealed no change in size of the vegetation. The patient has

Figure 4. Serial chest radiographs of the patient presented in case 2 taken 10 days apart. While the infiltrate in the left lower lobe of the lung has cleared, a new infiltrate in the right lower lobe has appeared.

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remained asymptomatic without cardiac medications after 2V2 years of follow-up observation. Comment. At least 80% of patients with infective endocarditis have mild anemia-that is, a hematocrit value between 33% and 38% and a hemoglobin level between 10.5 and 12.9 g/dl. The anemia is rarely severe or hemolytic unless the prosthetic valve malfunctions with or without paravalvular leaks. Because it is mild and nonspecific, the anemia is often ignored, is labeled as anemia of chronic disease, or at times is treated unsuccessfully with iron and vitamin supplements. The anemia, which is normochromic and normocytic, results from bone marrow suppression, specifically ineffective erythropoiesis. This case illustrates that right-sided endocarditis and unusual organisms can occur in patients not addicted to drugs. A dental examination is advised in patients with endocarditis caused by S. viridans, as well as in endocarditis resulting from other oral flora organisms. Case 3. Late Embolic Complication From a Sterile Vegetation. A previously healthy 58-year-old woman (gravida 8, para 4, abortions 4) complained of recurrent fever over a 3-month period. A 2-week course of orally administered cephalexin (Keflex) was prescribed for a presumed urinary tract infection. However, recurrent fever, anorexia, and generalized fatigue prompted hospitalization. On admission, the patient's temperature was 38.4°C (101. 2°F); she was normotensive and in sinus tachycardia interrupted by frequent ventricular premature beats. A harsh IIINI pansystolic murmur heard over the entire precordium was increased with the Valsalva maneuver. No peripheral signs of endocarditis were seen. The hemoglobin level was 13.2 g/dl, white blood cell count was 12,600/mm3 with a shift to the left, and erythrocyte sedimentation rate was 50 mm/h by the Westergren method. Multiple cultures of blood grew Streptococcus intermedius. Echocardiography showed mitral valve prolapse with vegetation attached to the atrial side of the posterior mitral leaflet (Fig. 5). Bacteriologic cure was achieved after 2 weeks of penicillin and streptomycin therapy. Six weeks after the completion of antibiotic therapy, the patient was asymptomatic, although echocardiography revealed an enlarging vegetation. Antiplatelet agents were prescribed. Ten weeks after completion of antibiotic therapy, the patient was readmitted to the hospital because of a painful lesion on the left foot. A skin biopsy documented superficial infarction and necrosis. Results of multiple blood cultures were negative. No atheromatous aortoiliac disease was demonstrated angiographically. However, a small embolus to the left peroneal artery was seen (Fig. 6). The patient recovered uneventfully and took Coumadin for 1 year. At follow-up examination 2 years after discovery of the systemic embolus, echocardiographic findings revealed no change in the size of the vegetation. The patient has remained asymptomatic without cardiac medication. Comment. Systemic embolization, a common early presentation of infective endocarditis,12 is relatively uncommon several months after therapy. Large exuberant vegetations commonly noted in patients with mitral valve prolapse and infective endocarditis 19 confer a higher risk of the development of embolization. We currently rely on serial echocardiographic

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Figure 5. Parasternal echocardiographic view recorded in systole in the patient discussed in case 3. Note the mitral valve vegetation (stippled area) protruding into the left atrial cavity. In a real-time motion study, this mobile vegetation was seen attached to the atrial side of the posterior mitral leaflet. A = anterior. AML = anterior mitral leaflet. Ao = aortic root. I = inferior. LA = left atrium. LV = left ventricle. P = posterior. RV = right ventricle. S = superior. (From Naggar, C. Z.: Two-Dimensional Echocardiography. [slide presentation] Garden Grove, California, Medcom, Inc., 1982; with permission.)

Figure 6. Femoral arteriogram showing the abrupt cutoff (arrow) of the left peroneal artery from a sterile embolus. The embolus was responsible for a localized skin infarct on the sole of the left foot.

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studies to identify patients with enlarging vegetations to guide our clinical management of such patients. Case 4. Recurrent Strokes Complicating Vegetative Endocarditis. A 57-year-old man with a past medical history of an idiopathic seizure disorder complained of fever, weakness, and backache for 2 months. The backache, thought to be musculoskeletal in origin, did not respond to analgesic agents and conservative management. The patient was admitted to another hospital with a fever of 38. goC (102°F); a pansystolic murmur (grade IIIVI) was heard over the apex; the erythrocyte sedimentation rate was 150 mm/h by the Westergren method; and a rheumatoid factor titer of 1:5280 was recorded. Several blood cultures grew S. viridans. Echocardiographic findings were reportedly normal. Radiography of the lumbosacral spine showed no evidence of osteomyelitis. Therapy with intravenously administered penicillin precipitated a rash and interstitial nephritis. The level of blood urea nitrogen rose to 130 mg/dl, and the serum level of creatinine rose to 5.5 mg/dl. The hospital course was complicated by an episode of erosive gastritis with massive upper gastrointestinal tract bleeding. The patient was transferred to the Lahey Clinic for hemodialysis. Five weeks after institution of antibiotic therapy, a left hemiparesis developed suddenly. Echocardiographic findings demonstrated a large vegetation attached to the atrial side of the posterior mitral leaflet (Fig. 7) and mitral valve prolapse. A visual field defect consistent with a right occipital embolic stroke developed suddenly 4 days after the first embolic stroke. Computed tomography of the brain documented two defects consistent with two embolic strokes (Fig. 8). Repeat echo cardiography still demonstrated the large vegetation attached to the posterior mitral leaflet and normal left ventricular size and function. Results of blood cultures were negative. Because of recurrent embolic strokes, the patient underwent replacement of the mitral valve. Intraoperatively, most of the posterior mitral leaflet appeared destroyed by

Vegetation

Figure 7. An apical echocardiographic view recorded in systole shOWing an exuberant, bulky mitral valve vegetation (srippled area). In a real-time motion study, the vegetation was seen attached to and moving with the posterior mitral leaflet. A = anterior. I = inferior. LA = left atrium. LV = left ventricle. P = posterior. RV = right ventricle. S = superior. (From Naggar, C. Z.: Two-Dimensional Echocardiography. [slide presentation] Garden Grove, California, Medcom, Inc., 1982; with permission.)

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Figure 8. Computed tomographic scan of the brain showing the right occipital infarct (black arrows) and the right basal ganglia infarct (white arrows) in the patient presented in case 4.

the vegetative process. The vegetation was friable and was not well organized. Comment. The hemodynamic status of the patient traditionally dictates the necessity for early replacement of the valve. Progressive or severe congestive heart failure in aortic or mitral valve endocarditis is the classic indication for surgical intervention. The high mortality rate when these patients are treated medically justifies the risk for development of prosthetic valve endocarditis and dehiscence with early replacement of the valve. 2 • 36 In addition, in any patient who has more than one major embolus, especially if a large mobile vegetation is demonstrated on echocardiography, serious consideration should be given to valve replacement. This case history depicts just such a therapeutic problem. Case 5. Large Vegetation Mechanically Obstructing Mitral Blood Flow. A 39-year-old woman required replacement of the mitral valve for severe mitral stenosis. A porcine heterograft was used. Two months after this procedure, the patient underwent successful cardioversion. The patient remained in normal sinus rhythm, free of symptoms, for 18 months after surgery. Recurrent fever and fatigue necessitated hospitalization when numerous blood cultures grew S. epidermidis. Echocardiographic findings showed a large vegetation attached to the porcine cusps of the prosthetic mitral valve obstructing inflow to the mitral valve (Fig. 9). Although the patient's fever abated with appropriate antibiotic therapy, diffuse purpuric lesions associated with hemolytic anemia, thrombocytopenia, and a con-

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LA

Porcine prosthetic valve

Figure 9. Parasternal echocardiographic view parallel to the long axis of the left ventricle, recorded in systole in the patient discussed in case 5. The porcine mitral prosthesis was visualized. Note the large vegetation (stippled area) attached to the porcine cusps. A = anterior. Ao = aortic root. I = inferior. LA = left atrium. LV = left ventricle. P = posterior. RA = right atrium. S = superior.

sumption coagulopathy developed. Pulmonary edema (Fig. 10) ensued, and a low cardiac output syndrome evolved rapidly. Emergency replacement of the valve was unsuccessful. Comment. Prosthetic valve endocarditis is frequently caused by organisms other than S. viridans. Infections of a prosthetic valve are frequently associated with hemodynamically severe valvular dysfunction and myocardial abscesses. Valvular obstruction is a rare complication of prosthetic

Figure 10. Chest radiograph showing bilateral pleural effusion and severe pulmonary vascular congestion in the patient discussed in case 5. The opaque sternal wires and the mitral valve prosthesis are well visualized.

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valve endocarditis. These large exuberant vegetations are occasionally found in patients with mitral valve prolapse or in patients with porcine heterografts. In this patient, the large vegetation caused both mechanical impedance to blood How from the left atrium to the left ventricle and serious hemolytic and bleeding diathesis.

Clinical Experience With Infective Endocarditis We have reviewed our experience from 1967 through 1983 with 58 consecutive patients grouped into patients treated before and after the widespread use of echocardiography. Such a grouping proved useful in demonstrating the evolutionary trends of infective endocarditis in two successive periods (Table 1). Although patients with rheumatic heart disease constitute the largest group (7 of 23, or 30%) of patients with infective endocarditis from 1967 through 1974, patients with mitral valve prolapse accounted for the majority (19 of 35, or 54%) of patients with infective endocarditis seen from 1975 through 1983. The current literature 4 supports our observation that mitral valve prolapse has replaced rheumatic heart disease as the most common disease predisposing patients to the development of infective endocarditis. Infective endocarditis remains predominantly a disease of men. 6 We observed a 2.8:1 and a 3.4:1 male-to-female ratio in the two successive periods and a lower mean age (48 years) in the more recent group compared with 52 years in the earlier group. Such a difference is partly explained by the fact that 23% of patients in the recent group, all of whom had mitral valve prolapse, contracted infective endocarditis before the age of 40. S. viridans remains the most common offending organism in both groups of patients. The increased incidence of staphylococcal endocarditis in the more recent group is related to the increasing number of patients

Table I. Differences Among Patients With Infective Endocarditis in Two Successive Periods GROUP!

No. of patients Mean age (years) Male:female ratio Underlying heart disease Rheumatic Congenital Mitral valve prolapse Prosthetic valve Other None Bacteriologic organism Staphylococci Streptococcus viridans Streptococcus--other Gram-negative Culture-negative

GROUP II

(1967-1974)

(1975-1983)

23 52 17:6

35 48 27:8

7 1 3 0 1 11

1 3 19 4 2 6

4 9 5 2 3

9 17 5 2 2

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Table 2. Microbiology of Infective Endocarditis* KO. Of PATlEKTS

ORGAKISM

Streptococcus S. viridans Other Staphylococcus S. aureus S. epidennidis Gram-negative and gram-positive bacilli Diphtheroids Pseudomonas aeruginosa Enteric gram-negative bacilli Fungi Other organisms Negative blood cultures Total

WITH K ATlYE

KO. OF I'ATIEKTS

VALVE

WITH PROSTHETIC

ADDICTS WITH

EKDOCARIJITIS 17

EKDOCARDITIS l4

ENDOCARDITIS"

NO. OF :'-iARCOTIC

149 79

64 52

28 45

72 16 35

65 130

208 9

NS NS NS

0 29 13

30 0 69 43 9 0

2 16 12 16 27

393

462

380

17

*Adapted from Naggar, C. Z., and Forgacs, P.: Infective endocarditis: A disease in evolution. In Messerli, F. H. (ed.): Current Clinical Practice. Philadelphia, W. B. Saunders Co., ill press. NS = not specified.

with prosthetic valve endocarditis. Table 2 contrasts the frequency distribution of various causative organisms in three large series of patients with native valve 37 and prosthetic valve endocarditis 14 and with endocarditis in drug addicts. 24

Mitral Valve Prolapse and Infective Endocarditis The subgroup of patients with mitral valve prolapse and infective endocarditis deserves emphasis. Reports have established a 5. 3-fold9 to 8.6fold 3 increased risk l6 . 17 for infective endocarditis in patients with mitral valve prolapse. Moreover, men with mitral valve prolapse and systolic murmur are at considerably higher risk for development of infective endocarditis than women (7.7 versus 3.0 increased risk relative to the normal population).9 Of our 19 patients with mitral valve prolapse and infective endocarditis, 15 were men. Infective endocarditis is a more frequent complication in male patients with mitral valve prolapse, while in a free-living population 27 the incidence of mitral valve prolapse is three times more common in women than in men. Endocarditis developed before the age of 40 years in 42% of our patients with mitral valve prolapse (8 of 19 patients), although continued susceptibility to infective endocarditis in elderly patients with mitral valve prolapse is well documented. 30 A high incidence of vegetations (68%) was demonstrated echocardiographically in patients with mitral valve prolapse and infective endocarditis. Furthermore, multiple vegetations in the same patient are common. The clinical danger of these vegetations resides in their potential to embolize. Patients with mitral valve prolapse and infective endocarditis with demonstrable vegetation seen on echocardiography have

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higher incidences of systemic emboli, clinical congestive heart failure, and mitral valve operation. 19 Even though infective endocarditis in patients with mitral valve prolapse is usually responsive to antimicrobial therapY,20 serious complications, such as major systemic emboli, ruptured chordae tendineae, and severe mitral regurgitation, are common.

Impact of Echocardiography on Clinical Management and Follow-Up Study of Patients With Infective Endocarditis Two-dimensional echocardiography provides the most complete anatomic study of the beating heart. 18 It visualizes cardiac valves with a high degree of resolution. When performed by experienced personnel, echocardiography is a sensitive technique that is capable of demonstrating intracardiac masses, such as vegetation, tumors, or clots. Noninvasive visualization of bacterial and fungal vegetations in vivo represents a definite diagnostic advantage. 5. 21. 26 In our series of 35 consecutive patients with infective endocarditis treated from 1975 through 1983, routine diagnostic echocardiography demonstrated 24 vegetations on native valves of 19 patients. Figure 11 shows the distribution of these vegetations. A large exuberant vegetation seen in the patient with a porcine mitral valve prosthesis caused severe obstruction of the inflow to the mitral valve and low cardiac output. In two other patients with Bjork-Shiley aortic cardiac valve prostheses (Shiley, Inc., Irvine, California), echo cardiography was equivocal for the presence of vegetations. This occurrence highlights the lack of sensitivity of echo cardiography in visualizing bacterial vegetations in the presence of highly reflective prosthetic valves. Within the first 12 weeks of antibiotic therapy, 12 of 25 vegetations increased in size, three became more mobile, and five of 18 extended to the chordae tendineae. However, in the late follow-up period, an average of 160 weeks after antibiotic therapy, 18 of23 vegetations remained unchanged in size, one increased, and one decreased. Echocardiographic findings contributed to decisions for early surgical intervention in two patients and demonstrated enlarging vegetations in two other patients with recurrent systemic emboli. We recommend that echocardiography be repeated every 8 to 10 days during antibiotic therapy in patients with initially demonstrable vegetations. In recent years, echocardiography has played an important role in the diagnosis of infective endocarditis (cases 1 and 2) and in clinical management (cases 3 and 4). In addition to its ability to image bacterial vegetations on the valvular surface accurately, I. 29 echocardiography defines the size, mobility, and natural history of these vegetations; the degree of valvular destruction; the hemodynamic derangement caused by infective endocarditis; and left ventricular function.

Conclusions Infective endocarditis is a disease in evolution, often presenting the physician with diagnostic and therapeutic challenges. In the last decades we have witnessed a change from rheumatic disease to mitral valve prolapse

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NCC In=2) RCC In=4) \ \ \

A.

I

CT In=4) I

I

I AML In=9) PML In =81

TSL .....

In=1)

- CT In=41 -AML In=91 - PML!n=81

B.

TSL-

In=11 RCC-In=4) NCCIn=2)

Figure 11. Schematic diagram of three echocardiographic planes demonstrating the distribution of 24 vegetations in our series of 19 patients with native valve infective endocarditis. (A) Longitudinal parasternal view. (8) Four-chamber apical view. (C) Short axis view at the level of the great vessels. A = anterior. AML = anterior mitral leaflet. Ao = aortic root. CT = chordae tendineae. I = inferior. L = left. LA = left atrium. LV = left ventricle. NCC = noncoronary cusp of the aortic valve. P = posterior. PA = pulmonary artery. PML = posterior mitral leaflet. R = right. RA = right atrium. RCC = right coronary cusp of the aortic valve. RV = right ventricle. RVOT = right ventricular outflow tract. S = superior. TSL = tricuspid septal leaflet.

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as the major heart disease predisposing patients to the development of endocarditis. With successful antimicrobial therapy, the complications rather than the infection pose the major therapeutic problems. In addition to progressive heart failure, myocardial abscesses, and relapsing prosthetic valve endocarditis, major systemic emboli in the presence of large protuberant vegetations constitute indications for replacement of the valve. We have used anticoagulant agents cautiously and successfully to prevent recurrent emboli in patients with infective endocarditis. We believe that echocardiography contributes greatly to the diagnosis and management of infective endocarditis.

REFERENCES 1. Bleese, N., Riidlger, W., Ayisi, K., et al.: The reliability of echocardiography in the preoperative diagnostics of bacterial endocarditis. Thorac. Cardiovasc. Surg., 30:354-357, 1982. 2. Borst, H. G., Hetzer, R., and Deyerling, W.: Surgery for active infective endocarditis. Thorac. Cardiovasc. Surg., 30:345-349, 1982. 3. Clemens, J. D., Horwitz, R. 1., Jaffe, C. C., et al.: A controlled evaluation of the risk of bacterial endocarditis in persons with mitral-valve prolapse. N. Eng\. J. Med., 307:776-781, 1982. 4. Corrigall, D., Bolen, J., Hancock, E. W., et al.: Mitral valve prolapse and infective endocarditis. Am. J. Med., 63:215-222, 1977. 5. Dillon, T., Meyer, R. A., Korfhagen, J. c., et al.: Management of infective endocarditis using echocardiography. J. Pediatr., 96:552-558, 1980. 6. Durack, D. T., and Beeson, P. B.: Pathogenesis of infective endocarditis. In Rahimtoola, S. H. (ed.): Infective Endocarditis. New York, Grune & Stratton, 1978, pp. 1-47. 7. Geraci, J. E., and Wilson, W. R.: Endocarditis due to gram-negative bacteria: Report of 56 cases. Mayo Clin. Proc., 57:145-148, 1982. 8. Hermans, P. E.: The clinical manifestations of infective endocarditis. Mayo Cli». Proc., 57:15-21, 1982. 9. Hickey, A. J., MacMahon, S. W., and Wilcken, D. E. L.: When is antibiotic prophylaxis necessary in mitral valve prolapse? (abstract) Circulation, 70:11-102, 1984. 10. Jefferys, D. B., Smith, S., Brennand-Roper, D. A., et al.: Acupuncture needles as a cause of bacterial endocarditis. Br. Med. J., 287:326-327, 1983. 11. Johnson, C. M., and Rhodes, K. H.: Pediatric endocarditis. Mayo Clin. Proc., 57:86-94, 1982. 12. Jones, H. R., Jr., Siekert, R. G., and Geraci, J. E.: Neurologic manifestations of bacterial endocarditis. Ann. Intern. Med., 71 :21-28, 1969. 13. Keys, T. F.: Antimicrobial prophylaxis for patients with congenital or valvular heart disease. Mayo Clin. Proc., 57: 171-175, 1982. 14. Mayer, K. H., and Schoenbaum, S. C.: Evaluation and management of prosthetic valve endocarditis. Prog. Cardiovasc. Dis., 25:43-54, 1982. 15. Melvin, E. T., Berger, M., Lutzker, L. G., et al.: Noninvasive methods for detection of valve vegetations in infective endocarditis. Am. J. Cardio\., 47:271-278, 1981. 16. Mills, P., Rose, J., Hollingsworth, J., et al.: Long-term prognosis of mitral valve prolapse. N. Eng\. J. Med., 297:13-18, 1977. 17. Naggar, C. Z.: The mitral valve prolapse syndrome: Spectrum and therapy. Med. Clin. North Am., 63:337-353, 1979. 18. Naggar, C. Z.: Two-dimensional echocardiography: Viewing the heart in motion. Postgrad. Med., 75:68-82, 1984. 19. Naggar, C. Z., Pippin, J., and Forgacs, P.: Infective endocarditis: A changing disease. (abstract) Chest, 86:316, 1984. 20. Nolan, C. M., Kane, J. J., and Grunow, W. A.: Infective endocarditis and mitral prolapse: A comparison with other types of endocarditis. Arch. Intern. Med., 141:447-450, 1981. 21. Popp, R. L.: Echocardiography and infectious endocarditis. In Remington, J. S., and Swartz, M. V. (eds.): Current Clinical Topics in Infectious Disease. Volume 4. New York, McGraw-Hill Book Co., 1983, pp. 98-110.

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