Infective Endocarditis in King Faisal Specialist Hospital: A Review of 35 Consecutive Adult Patients

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1 Infective Endocarditis in King Faisal Specialist Hospital: A Review of 35 Consecutive Adult Patients Murtada A. Halim, MRCP* M. Oussama Jeroudi, MD Edward N. Mercer, MD, FRCP(C), FACC M. Eid Fawzy, MRCP, FACC Galal Ziady, MD, FCCP, FACC * Consultant Cardiologist, Armed Forces Hospital, Riyadh; Resident; Staff Cardiologist; Staff Cardiologist; Staff Cardiologist, Department of Medicine, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia Date of Acceptance: 12 February 1986 ABSTRACT Thirty-five adult patients with an established diagnosis of infective endocarditis were treated at the King Faisal Specialist Hospital between 1976 and There were 26 males and 9 females with a mean age of 32 years. Endocarditis was found on a native valve in 14 patients, on a prosthetic valve in 14, on a congenital lesion in 6, and 1 patient had dilated cardiomyopathy. Positive blood cultures were obtained in 25 patients (71%). The commonest infective organism of native valves was Streptococcus viridans and of prosthetic valves was Staphylococcus epidermidis. Brucella accounted for 3 cases. Echocardiogram was available in 27 patients and vegetation could be demonstrated in 14 (52%). Pericardial effusion was seen in 6 patients and was associated with a high complication rate. Twelve patients needed early surgery with 3 deaths (25%) resulting. The indications for early surgery in the active stage were hemodynamic deterioration in 7, persistent infection in 4 and fear of embolism in one. Five patients had elective surgery with no mortality. All Brucella endocarditis patients needed early surgery. In the whole group there were seven early deaths, and two late deaths in a mean follow-up period of 35 months. M A. Halim, M. O Jeroudi, E N. Mercer, M. E Fawzy, G Ziady, Infective Endocarditis in King Faisal Specialist Hospital: A Review of 35 Consecutive Adult Patients. 1986; 6(3): MeSH KEYWORDS: Endocarditis Saudi Arabia Introduction THE CLINICAL PRESENTATION, pathological findings and response to medical and surgical treatment of infective endocarditis from various cardiac centers has been reported. In this study we report our experience with infective endocarditis from a tertiary care center in Saudi Arabia, reflecting on the local characteristics of the disease and results of treatment. Patients and Methods All patients with an established diagnosis of infective endocarditis admitted to the hospital between August 1976 and March 1985 were included. Doubtful cases were excluded. The criteria for establishing the diagnosis were: strong clinical evidence of the disease in patients with established cardiac lesions, supported by microbiological cultures of blood or surgical specimens or surgical findings. Patients' data were analyzed for symptoms at presentation, site of endocarditis, previous cardiac surgery, blood cultures, and possible other tests for causative organisms. Echocardiography was used in detecting vegetations and identifying complications. The indications for and results of surgery were also analyzed. Results There were 26 males and 9 females with a mean age of 32 years (range 15 76). All patients except one presented with fever and fatigue. Twenty-eight patients (80%) had shortness of breath and 6 patients (17%) had embolic episodes. The sites of the embolic episodes were cerebrovascular (2 patients), retinal artery, femoral artery, brachial artery and coronary artery. At the time of admission, 7 patients were in Class I (New York Heart Association Classification), 9 in Class II, 13 in Class III and 6 in Class IV.

2 Site of Infection Endocarditis was on a native valve in 14 patients, on a valve prosthesis in 14, on a congenital lesion in 6 and 1 patient had dilated cardiomyopathy (Table 1). The affected congenital lesions are shown in Table 2. Five of the involved native valves were mitral, and 9 were aortic. Of the 14 patients with previous valve replacement, 7 had endocarditis on a replaced mitral valve, 6 on a replaced aortic valve, and 1 patient, who had mitral and aortic valve replacement, died before the site of endocarditis could be established. Table 1. Pre-existing cardiac disease and site of endocarditis Site of endocarditis Number of patients Normal or no documented previous 3(all aortic valve) heart disease Rheumatic heart disease Total 11 mitral valve 5 aortic valve 6 Prosthetic valve (bioprosthesis 7, mechanical 7) Total 14 mitral (bioprosthesis 5, mechanical 2) 7 aortic (bioprosthesis 1, mechanical 5) 6 undetermined 1 (had MVR and AVR) 1 Congenital heart disease 6 Cardiomyopathy 1 Table 2. Congenital lesions affected and their causative organism in six patients Tetralogy of Fallot Truncus arteriosus Patent ductus arteriosus Coarctation of aorta Subaortic membrane Pulmonary stenosis S. viridans S. viridans S. aureus S. aureus S. aureus N. gonorrhea Microbiology Positive blood cultures were obtained in 25 patients (71%). In 10 patients the blood cultures were negative; of these, 8 had received antibiotic therapy before referral. One of the 8 had a very high titer for Brucella, and at the time of surgery, Brucella was cultured from the excised aortic cusp. The causative organisms are shown in Table 3 as determined from cultures of blood or surgical specimens. Streptococcus viridans was the commonest causative organism in native valve endocarditis. Staphylococcus epidermidis was the commonest infective organism in prosthetic valve endocarditis. In fact, all 6 cases of Staphylococcus epidermidis occurred on prosthethic valves. Brucella affected 3 patients (8.5%) and the aortic valve was the site of infection in all three. Table 3. Causative organism twenty-six patients with positive culture Causative organism Number of patients S. viridans 8 S. epidermidis 6* S. aureus 5 Brucella 3 E. coli 1 N. gonorrhea 1 Actinobacillus 1 Eubacterium 1

3 * All on prosthetic valve Echocardiography Echocardiographic study was available for 27 of the affected patients. Vegetations were demonstrated in 14(52%) of these. Eight had vegetation on the aortic valve, 5 on the mitral valve and 1 on the pulmonary valve. Pericardial effusion was seen in 6 patients and was associated with a high complication rate. One died early and 4 needed emergency surgery. Additional echocardiographic findings in these patients included mycotic aneurysms of the ascending aorta in 2 patients, a false aneurysm of the ascending aorta in 1, and an aortic root abscess in a fourth. These findings were confirmed at surgery. All 3 patients with aortic valve Brucella endocarditis showed bulky vegetations. In one, the aortic cusp was nearly detached with the vegetation prolapsing into the left ventricular outflow tract. Vegetations were seen by echocardiography in 3 culture-negative patients and this helped to confirm the diagnosis. Medical Treatment All patients received antibiotics intravenously as soon as the diagnosis was strongly suspected clinically, and a minimum of three sets of blood cultures were taken. The antibiotics used were chosen according to the sensitivity of the organisms. Before the blood cultures were available, and in culture-negative patients, a combination of aminoglycoside (gentamicin or amikacin) and crystalline penicillin (20 million units/day) was prescribed. Antibiotic therapy was continued for at least six weeks. The first of 3 patients with Brucella was treated with intravenous septra; (trimethoprim sulfa methoxazole); and lately we used a combination of septra and rifampicin. Treatment was continued for a minimum of six months in all 3 patients. Surgical Treatment In the study group, surgery was needed in 17 patients (48%). It was performed in the active stage of the disease before completion of the course of antibiotics in 12 patients and after completion of antibiotic therapy in the other 5. The indications for early surgery in the 12 patients with active infection were hemodynamic deterioration in 7, persistent infection in 4, and fear of embolization in 1 patient because echocardiography showed a large vegetation prolapsing into the left ventricular outflow tract. There were three early deaths (25%) in this group. The distribution of the patients who needed early surgery is shown in Table 4. In the 5 patients who had elective surgery, the indication was hemodynamic sequelae of the endocarditis. There was no mortality. The outcome of 14 patients with prosthetic valve endocarditis deserves special mention. Two died early while on medical treatment prior to surgery, four needed early surgery in the active stage, and there was 1 death. Of the remaining 8 who were treated medically, 3 are alive and well, 3 needed later elective surgery, one died later, and one is lost to follow-up. Thus, of the 14 patients with prosthetic valve endocarditis 7(50%) required reoperation. Table 4. Site of endocarditis and causative organism in twelve patients with early surgery Site of endocarditis Prosthetic valves: Native valves: Subaortic membrane Patent ductus Organism 4 2 mitral (Staph. epidermidis, culture negative) 2 aortic (Strep. viridans, Staph epidermidis) 6 all aortic (3 Brucella, 1 Staph. aureus, 1 Strep. viridans, 1 culture negative) 1 (Staph. aureus) 1 (Staph. aureus) Mortality and Follow-up There were 7 early deaths (20%), 3 following emergency surgery and 4 while on medical treatment. The remaining 28 patients were discharged from the hospital and were followed for a mean duration of 35 months. There

4 were 2 late deaths, and 5 needed replacement of the affected valve. Four patients were lost to follow-up. Discussion In spite of advances in medical and surgical management, infective endocarditis still has a high mortality and morbidity. In the Middle East, where there is a high prevalence of rheumatic heart disease, we see a mixture of native valve endocarditis and prosthetic valve endocarditis. Our patients are young: their mean age was 32 years, which is similar to the average age found by Ross, et al, 1 in Riyadh Military Hospital, and in the West from This reflects the prevalence of rheumatic heart disease in the Kingdom. None of the cases was secondary to drug addiction. Microbiology Streptococcus viridans remains the most common organism affecting native valves (38%). In prosthetic valve endocarditis Staphylococcus epidermidis was the most common organism, as in other reports. 3,4 Seventy-one percent of the blood cultures were positive. Of the 10 patients who were culture negative, 8 were on antibiotics empirically before referral. Thus, it is clear that every attempt must be made to obtain a blood culture before the start of treatment. Although we obtained only a minimum of three blood cultures in this retrospective analysis, we agree with the recommendation that at least six separate sets of blood cultures should be obtained within a period of 48 hours. 5 A two-day delay before treatment will not cause serious mortality or morbidity in patients with subacute endocarditis. If death occurs during such a delay, it is usually due to complications of the disease which could not be prevented by antibiotic therapy. 6 However, in acute bacterial endocarditis, therapy should be started immediately. Brucella endocarditis accounted for 8.5% (3 cases), which is a high incidence. 7 In these 3 cases (all males) the aortic valve was involved, all were associated with large vegetation on echocardiography and complications which required early surgery. Two patients needed surgery for hemodynamic deterioration and in a third patient there was a bulky vegetation prolapsing to the left ventricular outflow tract necessitating operation because of fear of fatal embolism. In Brucella endocarditis, blood cultures may be negative initially due to the slow growth of the organism but the Brucella titer is usually high. We consider that in patients with culture negative endocarditis, a high Brucella titer and the presence of bulky vegetation on echocardiography may be helpful in diagnosing the causative organism. Echocardiography In the past decade, the development of echocardiography has had significant impact on the diagnosis and management of endocarditis. Dillon 8 first reported on the value of M-mode and concluded that vegetations larger than 2mm could be identified. Two-dimensional echocardiography was found to be superior to M-mode and is particularly useful in patients with prosthetic valve endocarditis. 9,10 The diagnostic value of echocardiography depends primarily on the demonstration of vegetations. The diagnostic accuracy varied in the reported series from 13% to 78%. 11,12 Our diagnostic accuracy was 52%. These variations in diagnostic accuracy must be considered in the light of many variables: the frequency with which microscopic vegetations occur in cases of endocarditis; 13 that it is unlikely that vegetation smaller than 2 mm will be identified; pre-existing thickening and calcification of valves make interpretation difficult, and that it is also difficult to differentiate healed from active endocarditis. 10,14 Finally, the timing of the echocardiography study in relation to onset of illness has diagnostic significance. Beside the diagnostic value, echocardiography may be helpful in detecting complications. Four of the patients with aortic valve endocarditis showed abscess or mycotic aneurysms on echocardiography. Brandenburg 5 reported a similar incidence of myocardial abscess detected by echocardiography. Though documentation of abscess alone is not a clear indication for surgery, more often than not it will be necessary. All four patients in our series with abscess or mycotic aneurysm needed early surgery. Pericardial effusion was another echocardiography finding and was associated with complications such as aortic root abscess, mycotic aneurysm, or false aneurysm. It was detected in 6 patients, of whom 4 needed emergency surgery because of persistent infection and another who died soon after admission. Echocardiography was also useful in assessing the acute and chronic hemodynamic sequelae of valvular incompetence produced by the endocarditis. In acute aortic regurgitation, early closure of the mitral valve is considered an indication for surgery as it reflects a marked elevation of left ventricular end-diastolic pressure. 15,16 In patients cured of infection and who had aortic regurgitation as a sequela, echocardiography was used for timing of elective aortic valve replacement by serial followup of their left ventricular dimensions and function.

5 Surgery Though the first reported case of surgical cure of endocarditis was in with ligation of an infected patent ductus, it was not until 1965 that the first valve replacement was described. 18 Subsequently surgery was more frequently performed in the active stage with improved survival. 19,20,21 It has been found that in spite of the potent antibiotics, a group of patients remained who required early surgical intervention because medical therapy was ineffective. The indications for early surgery in our patients were: hemodynamic deterioration in 7; persistent infection in 4, and fear of embolism in 1 patient with aortic valve Brucella endocarditis. These are the accepted criteria for early surgery; 22,23 though surgery for an embolic episode or fear of embolism is still controversial. 13,23 Our mortality from early surgery was 25%, similar to the experience of others. 19,23 Recently, in prosthetic valve endocarditis there has been a tendency toward early surgery because medical treatment is associated with a high mortality (60 70%). 5,25,26 The number of patients with prosthetic valve endocarditis in this study is too small to make any comparison. Late surgery was performed in 5 patients with no mortality. Thus, although elective surgery following a full course of antibiotics is associated with less mortality, surgery should not be delayed in the group who need it early for hemodynamic deterioration or persistent infection, as medical treatment alone is associated with high mortality. REFERENCES 1. Ross J, Al-Faghi M, Al-Zaibag MA, et al. The medical and surgical management of infective endocarditis. Saudi Med J 1982; 3(4): Hamburger M. Acute and subacute bacterial endocarditis. Arch Int Med 1963; 112: Masur H, Johnson WD Jr. Prosthetic valve endocarditis. J Thorac Cardiovasc Surg 1980; 80(1): Invert TS, Dismukes WE, Cobbs CG, et al. Prosthetic valve endocarditis. Circulation 1984; 69(2): Brandenburg RO, Giuliani ER, Wilson WR, Geraci JE. Infective endocarditis a 25 year overview of diagnosis and therapy. J Am Coll Cardiol 1983; 1(1): Weinstein L. Infective endocarditis. In: Braunwald E, ed. Heart Disease. 2nd ed. Philadelphia: WB Saunders, 1984: Cohen PS, Maguire JH, Weinstein L. Infective endocarditis caused by gram-negative bacteria: a review of the literature Prog Cardiovasc Dis 1980; 22(4) Dillon JC, Feigenbaum H, Koneck LL, et al. Echocardiographic manifestations of valvular vegetations. Am Heart J 1973; 86: Martin RP, Meltzer RS, Chia BL, et al. Clinical utility of two dimensional echocardiography in infective endocarditis. Am J Cardiol 1980; 46(3): Mintz GS, Kotler MN, Segal BL, et al. Comparison of two dimensional and M-mode echocardiography in the evaluation of patients with infective endocarditis. Am J Cardiol 1979; 43(4): Come PC, Isaacs RE, Riley MF. Diagnostic accuracy of M-mode echocardiography in active infective endocarditis and prognostic implications of ultrasound detectable vegetations. Am Heart J 1982; 103(5): Stewart JA, Silimperi D, Harris P, et al. Echocardiographic documentation of vegetative lesions in infective endocarditis: clinical implications. Circulation 1980; 61(2): Buchbinder NA, Roberts WC. Left-sided valvular active infective endocarditis: a study of forty-five necrospy patients. Am J Med 1972; 53: Stafford A, Wann SL, Dillon JC, et al. Serial echocardiographic appearance of healing bacterial vegetation. Am J Cardiol 1979; 44(4): Pridie RB, Benham R, Oakley CM. Echocardiography of the mitral valve and aortic valve disease. Br Heart J 1971; 33: Botvinick EH, Schiller NB, Wickramasekaran R, et al. Echocardiographic demonstration of early mitral valve closure in severe aortic insufficiency: its clinical implications. Circulation 1975; 51(5): Touroff ASW, Vessell H. Subacute Streptococcus viridans endarteritis complicating patent ductus arteriosus. JAMA 1940; 115: Wallace AG, Young WG Jr, Osterhout S. Treatment of acute bacterial endocarditis by valve excision and replacement. Circulation 1965; 31:

6 19. Perry LS, Tresch DD, Brooks HL, et al. Operative approach to endocarditis. Am Heart J 1984; 108(3 Pt 1): Richardson JV, Karp RB, Kirklin JM, Dismukes WE. Treatment of infective endocarditis: a 10-year comparative analysis. Circulation 1978; 58(4): Wilson WR, Danielson GD, Giuliani ER, et al. Valve replacement in patients with active infective endocarditis. Circulation 1978; 58(4): McAnulty JH, Rahimtoola SM. Surgery for infective endocarditis. JAMA 1979; 242(1): Stinson SB. Surgical treatment of infective endocarditis. Prog Cardiovasc Dis 1979; 22: Davis RS, Stom JA, Frishman W, et al. The demonstration of vegetations by echocardiography in bacterial endocarditis. An indication for early surgical intervention. Am J Med 1980; 69(1): Sandza JG Jr, Clark RE, Ferguson TB, et al. Replacement of prosthetic heart valves. J Thorac Cardiovasc Surg 1977; 74(6): Saffle JR, Gardner P, Schoenbaum SC, et al. Prosthetic valve endocarditis. The case for prompt valve replacement. J Thorac Cardiovasc Surg 1977; 73(3)