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Multi-valvular endocarditis
ORIGINAL ARTICLE
Multi-valvular endocarditis N. Kim1, J. M. Lazar2, B. A. Cunha1, W. Liao2 and V. Minnaganti1 1
Infectious Disease Division and the 2Division of Cardiology, Winthrop-University Hospital, Mineola, New York
Objective Seventy-seven cases of native valve infective endocarditis as determined by the Duke criteria, were
reviewed to determine the incidence and clinical features of multi-valvular endocarditis. Methods Fourteen of 77 patients (18%) had multi-valvular endocarditis most commonly involving the mitral
and aortic valves. Staphylococcus aureus (43%) and viridans streptococci (36%) were the most common organisms causing multi-valvular endocarditis. Results Definite or probable vegetations were found in 50% of the patients by two-dimensional transthoracic
echocardiograph and/or transesophageal echocardiograph, and possible vegetations were detected in 21%. The overall mortality in our series was 21%; 29% underwent valve replacement and 50% were treated medically. The major complications of multi-valvular endocarditis were congestive heart failure (64%), acute renal failure (50%), embolic events (21%), and splenic abscess/infarcts (21%). Conclusions Our data suggests complications of multi-valvular endocarditis, compared with uni-valvular
endocarditis are similar except for heart failure. Heart failure is statistically more common in multi-valvular endocarditis (P ¾ 0.002). Keywords multi-valvular infective endocarditis Accepted 25 November 1999
Clin Microbiol Infect 2000; 6: 207–212
INTRODUCTION Infective endocarditis (IE) involving multiple cardiac valves is uncommon. The majority of echocardiographically demonstrated endocarditis occurs on a single valve; the involvement of two valves occurs much less frequently, and triple- or quadruple-valve involvement is extremely rare [1–6]. Demonstration of multi-valvular involvement in patients with suspected IE is important. Mortality rate is more likely to be higher in patients with infection of two or more valves than a single valve and these patients might require early operation for management of complications [7]. We reviewed the medical records of 77 patients with documented IE to study the incidence, presentation, outcome, and complications of multi-valvular endocarditis. METHODS The medical records of all adult patients with documented native valve IE were reviewed. Endocarditis was defined using Corresponding author and reprint requests: B. A. Cunha, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA Tel: +1 516 663 2505 Fax: +1 516 663 2753
the Duke criteria [8]. The patients were admitted to WinthropUniversity Hospital, a 600-bed, tertiary care, teaching hospital in Mineola, New York, between August 1990 and November 1994. Of 77 patients who met the Duke criteria for IE, 14 patients had multi-valvular endocarditis on the basis that septicemia was present in a febrile patient, with or without a new or changing heart murmur, who had more than one cardiac valve involvement demonstrated by two-dimensional (2-D) transthoracic echocardiograph (TTE), or transesophageal echocardiograph (TEE) images of vegetations, or by new regurgitation detected by Doppler echocardiography. Of 14 cases of multi-valvular endocarditis reviewed, information pertaining to demographic characteristics, predisposing factors, microorganisms involved, sites of infection, clinical and laboratory features, outcome, and complications were analyzed. Twentyfive patients with uni-valvular endocarditis were selected from the remaining 63 patients as age-matched controls.
RESULTS Results are summarized in Tables 1 and 2. Of 77 IE patients reviewed, 14 patients (18%) had multiple-valve involvement. These 14 patients were divided into two groups. Group I
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Figure 1 Transesophageal echocardiographic (TEE) images showing large echodensities on the mitral valve and the aortic valve.
included seven patients with underlying heart disease (e.g. mitral valve prolapse, rheumatic heart disease, congenital/acquired valvular diseases, a history of IE, etc.). Group II included seven patients with or without other known predisposing factors (e.g. alcohol abuse, steroid use, diabetes mellitus, etc.). All 14 cases of multi-valvular endocarditis involved two valves and there was no triple- or quadruple-valve endocarditis in our series. The patients’ age range was 31–96 years (mean 65 years). The male : female ratio was 4.3, equally divided in each group. In group I, the mean age was 62 years, whereas in group II the mean age was 68 years. Predisposing factors, which were found in various combinations in 11 of these 14 patients (79%), were mitral valve prolapse (two patients; 14%), rheumatic heart disease (one patient; 7%), congenital valvular disease–mitral stenosis (one patient; 7%), acquired valvular disease– aortic insufficiency (one patient; 7%), a history of IE (two patients; 14%), recent permanent pacemaker placement (one patient; 7%), recent dental procedure (two patients; 14%), recent abdominal surgery (one patient; 7%), intravenous drug abuse (one patient; 7%), alcohol abuse (one patient; 7%), steroid use (one patient; 7%), and diabetes mellitus (two patients; 14%). The etiologic micro-organisms found in these 14 patients were Staphylococcus aureus in six patients (43%)—three patients in each group; viridans streptococci (e.g. Streptococcus mutans, Streptococcus sanguis, and Streptococcus mitis) in five patients (36%)— three patients in group I and two patients in group II; and enterococci in two patients (14%)—one patient in each group. One patient in group II had two micro-organisms, Staphylococcus aureus and Klebsiella pneumoniae. This patient was treated with an anti-staphylococcal cephalosporin and an aminoglycoside, but unfortunately died. The valves most frequently involved were mitral and aortic valves (12 of 14 patients; 86%)—six patients in each group.
Mitral and tricuspid valves were involved in one patient in group I, and the aortic and tricuspid valves were involved in one patient in group II. We had no methicillin-resistant strains among patients infected with S. aureus in our series. All patients underwent 2-D TTE and Doppler echocardiography and some patients underwent TEE when necessary (Figure 1). We had no methicillin-resistant strains among patients infected with S. aureus. Definite or probable vegetations were found in seven of the patients (50%)—five patients in group I and two patients in group II, and possible vegetations were found in a further three of the 14 patients (21%)—one patient in group I and two patients in group II. All patients demonstrated on the Doppler echocardiogram mild to moderate regurgitation of affected valves. Clinically, a new or changing murmur was detected in seven of the 14 patients (50%)— two patients in group I and five patients in group II. Osler’s nodes, Janeway lesions, splinter haemorrhages, or petechiae were not, or rarely (in one to two patients), detected in the majority of our patients. Thirteen of 14 patients (93%) presented with fever (temperature ×100.6 °F, 38 °C) and chills. Among them, three patients (23%), all in group I, had temperatures ×102 °F (38.8 °C). Microscopic haematuria was a common finding (10 of 14 patients; 71%)—five patients in each group. Erythrocyte sedimentation rate (ESR) was elevated in all patients (100%) with a range of 26–108 mm/h. Two of 14 patients (14%), both in group II, had ESR × 100 mm/h. The overall mortality in our series was 21% (three of 14 patients)—one patient in group I and two patients in group II. Four of 14 patients (29%) underwent surgical intervention (multiple valve replacement or pacemaker replacement)—three patients in group I and one patient in group II. Seven of 14 patients (50%) were discharged after prolonged antibiotic therapy—three patients in group I and four patients in group II. The major complications among these 14 patients, in various combinations, were congestive heart failure (nine patients; 64%), acute renal failure (seven patients; 50%), embolic events (i.e. pulmonary emboli (PE), cerebral vascular accidents, disseminated intravascular coagulation, etc.) (three patients; 21%), splenic abscess or infarct (three patients; 21%), persistent bacteremia (two patients; 14%), meningitis (one patient; 7%), and liver necrosis (one patient; 7%). (Tables 1, 2) The characteristics of the uni-valvular control group are shown in Table 3. With the exception of congestive heart failure, the complications of multi-valvular and uni-valvular endocarditis were similar and not statistically different. Complications included acute renal failure, cerebral vascular accident, and congestive heart failure, and were not statistically different in patients with multi- or uni-valvular endocarditis. Congestive heart failure was a more frequent complication in the multi-valvular group, which was statistically different (P ¾ 0.002). The valve replacement surgery and mortality were not significantly different in both groups. (Table 4).
© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212
Aortic insufficiency RHD IVDU, h/o endocarditis Congenital MS h/o endocarditis MVP MVP, dental work 2 days PTA p.p.m. 2 months PTA
None
Steroid use None Recent tooth extraction None Recent abdominal surgery None
77 M 61 M 31 F 37 M
63 M
69 F 96 F 36 M 80 M 75 F 55 M
© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212 S. aureus (MSSA) S. aureus (MSSA) S. sanguis S. mitis Enterococci S. aureus (MSSA) K. pneumoniae
S. aureus (MSSA)
Enterococci
S. mutans S. viridans
S. aureus (MSSA) S. aureus (MSSA) S. aureus (MSSA) S. mutans
Micro-organism
MV,AV MV,AV MV,AV MV,AV MV,AV AV,TV
MV,AV
MV,AV
MV,AV MV,AV
MV,AV MV,AV MV,AV MV,AV
Valve
No No Yes No Probable Possible
Possible
Yes
Possible Yes
No Yes Yes Yes
Veg by echo
Yes Yes Yes No No Yes
Yes
Yes
No Yes
No No No No
New murmur
Yes No Yes No Yes Yes
Yes
Yes
Yes Yes
Yes Yes Yes Yes
Fever
15.1 7.4 12.2 11.5 11.9 13.1
10.5
14.9
8.2 8.7
13.3 8.8 6.9 10
WBC
79 29 64 26 108 108
46
90
37 83
53 53 79 99
ESR
Discharge Discharge MVR, AVR/discharge Discharge Discharge Death
p.p.m. replacement/ discharge Death
Discharge Discharge
Death MVR,AVR/discharge Discharge MVR,AVR/discharge
Outcome
CVA,meningitis, CHF, ARF, bacteremia, splenic infarct CHF CHF, ARF None None CHF CHF,ARF, liver necrosis, splenic infarct, DIC
CHF, ARF
None ARF
CHF, ARF, bacteremia, splenic infarct CHF PE, pancytopenia CHF
Complications
ARF, acute renal failure; AVR, aortic valve replacement; CHF, congestive heart failure; CVA, cerebral vascular accident; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; ESR, erythrocyte sedimentation rate; IVDU, intravenous drug user; MSSA, methicillin-sensitive Staphylococcus aureus; MS, mitral stenosis; MVP, mitral valve prolapse; MVR, mitral valve replacement; PTA, prior to admission; PE, pulmonary embolism; p.p.m, permanent pacemaker; RHD, rheumatic heart disease; WBC, white blood cell count; MV, mitral valve; TV, tricuspid valve; AV, aortic valve.
69 F
79 M 78 F
Predisposing factors
Age/Sex
Table 1 Multi-valvular endocarditis
Kim et al Multi-valvular endocarditis
209
Aortic Regurgitation Heart murmur None None RHD, dental work, 2 weeks PTA MVR Rheumatic fever, dental work 1 month PTA None None None MVP, mitral regurgitation MVP None None
None None, dental work 6 months PTA None Dental work 8 weeks PTA MVR
Past h/o endocarditis IVDA, endocarditis None MVP, endocarditis Dental work 1 month PTA AVR
42 M 36 M 62 F 49 F 80 F 64 F 67 M 74 M 81 F 71 F 81 F 38 M 58 F 83 F
42 M 51 M 38 M 25 M 68 F
36 F 44 M 36 M 61 F 44 M 68 M
S. viridans S. viridans S. sanguis S. sanguis S. viridans S. epidermidis (MSSE)
S. viridans S. viridans S. aureus (MSSA) S. sanguis S. viridans
S. mitis S. morbilorum S. defectivus S. sanguis S. viridans S. intermedius S. salivarius S. viridans S. viridans S. viridans S. constellatus S. viridans S. sanguis S. aureus (MSSA)
Micro-organism
VSD AV AV MV AV MV
MV MV TV AV MV
AV MV MV MV NA MV MV MV NA MV MV MV AV MV
Valve
NA Possible Yes Possible Possible No
No Yes Yes Yes Yes
Yes Yes Yes Yes No No Yes No Not done No No Possible Yes Yes
Veg by echo
No No No No Yes No
No No No Yes No
No No Yes No No No Yes No No No No No Yes Yes
New murmur
No Yes Yes Yes Yes Yes
Yes Yes No No Yes
Yes Yes Yes Yes Yes No Yes Yes Yes No No Yes No Yes
Fever
6.8 11.8 13.2 15.4 11.6 7.2
17.7 11.4 6.8 10.9 11.6
10.3 9.7 12.4 10.5 17.9 7.7 14 13.5 17.5 9.4 8.6 11.5 9.1 11.2
WBC
24 37 63 71 NA 14
NA 81 131 75 107
50 65 106 121 71 79 84 36 113 62 49 83 116 108
ESR
Discharge Discharge AVR/discharge Discharge Discharge Discharge
Discharge Discharge Discharge Discharge Discharge
Discharge Discharge Discharge Discharge Discharge Discharge MVR/discharge Discharge Death Discharge Discharge Discharge AVR/discharge MVR/death
Outcome
None ARF, renal abscess None None None None CHF None CVA, MI, CHF, ARF None None None CHF CHF, ARF, pulmonary oedema None CVA None None Osteomyelitis, T10–11, ARF None None NA None None None
Complications
ARF, acute renal failure; AVR, aortic valve replacement; CHF, congestive heart failure; CVA, cerebral vascular accident; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; ESR, erythrocyte sedimentation rate; MSSA, methicillin-sensitive Staphylococcus aureus; MS, mitral stenosis; MVP, mitral valve prolapse; MVR, mitral valve replacement; PTA. prior to admission; PE, pulmonary embolism; p.p.m., permanent pacemaker; RHD, rheumatic heart disease; WBC, white blood cell count; MV, mitral valve; TV, tricuspid valve; AV, aortic valve.
Predisposing factors
Age/Sex
Table 2 Valvular endocarditis (comparative group)
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© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212
Kim et al Multi-valvular endocarditis
Table 3 Multi-valvular endocarditis in the WinthropUniversity Hospital case series: controls/complications Number of patients = 14 Mean age (range) = 65 (31–96) years Male : female ratio = 8 : 6 Predisposing factors = 11/14 patients (79%) Mitral valve prolapse = 2/14 patients (14%) Rheumatic heart disease = 1/14 patients (7%) Congenital valvular disease (mitral stenosis) = 1/14 patients (7%) Acquired valvular disease (aortic insufficiency) = 1/14 patients (7%) History of infective endocarditis = 2/14 patients (14%) Recent permanent pacemaker placement = 1/14 patients (7%) Recent dental procedure = 2/14 patients (14%) Recent abdominal surgery = 1/14 patients (7%) Intravenous drug abuse = 1/14 patients (7%) Etiologic micro-organisms Staphylococcus aureus (MSSA) = 6/14 patients (43%) Viridans streptococci (Streptococcus mutans, S. sanguis, and S. mitis) = 5/14 patients (36%) Enterococci = 2/14 patients (14%) Staphylococcus aureus and Klebsiella pneumoniae (7%) Sites of infection Mitral valve and aortic valve = 12/14 patients (86%) Mitral valve and tricuspid valve = 1/14 patients (7%) Aortic valve and tricuspid valve = 1/14 patients (7%) Echocardiogram Definite/probable vegetation = 7/14 patients (50%) Possible vegetation = 3/14 patients (21%) No vegetation = 4/14 patients (29%) Clinical and laboratory features New or changing murmur = 7/14 patients (50%) Osler’s nodes = 0/14 patients (0%) Janeway lesions = 1/14 patients (7%) Splinter hemorrhages = 0/14 patients (0%) Petechiae = 2/14 patients (14%) Fever (T × 100.6 °F) = 13/14 patients (93%) (T × 102 °F) = 3/13 patients (23%) Chills = 13/14 patients (93%) Microscopic hematuria = 10/14 patients (71%) Elevated ESR (×20 mm/h) = 14/14 patients (100%) ESR range = 26–108 mm/h (ESR × 100 mm/h = 2/14 patients (14%)) Outcome and complications Death = 3/14 patients (21%) Surgical intervention (multi-valve replacement) = 4/14 patients (29%) Congestive heart failure = 9/14 patients (64%) Acute renal failure = 7/14 patients (50%) Embolic events = 3/14 patients (21%) Splenic abscess/infarct = 3/14 patients (21%) Persistent bacteremia = 2/14 patients (14%) Meningitis = 1/14 patients (7%) Liver necrosis = 1/14 patients (7%) ESR, erythrocyte sedimentation rate.
211
Post-mortem results were not obtained on any patient. Pathology following valve replacement was available in three patients with multi-valvular endocarditis and four patients in the uni-valvular group. Pathology reports were similar in both groups and were reported as having acute organizing inflammation, fibrin and calcium deposition associated with vascular and fibroblastic proliferation on the removed valve leaflets. All removed valve cells were negative for bacterial growth. DISCUSSION The occurrence of multi-valvular endocarditis is uncommon. The majority of IE cases involves a single valve, and demonstration of two-, triple-, or even quadruple-valve involvement by echocardiography is less frequent [1–6]. We reviewed the medical records of patients who were admitted to our hospital over a 4-year period with documented IE to determine the incidence and presentation of multi-valvular endocarditis using the Duke criteria [8]. We report here that among 77 patients with documented IE reviewed, there were 14 patients (18%) who had multi-valvular endocarditis, and 63 with uni-valvular endocarditis. Twenty-five age matched patients with uni-valvular endocarditis were selected as age-matched controls. Fourteen patients had two-valve involvement demonstrated by echocardiography and there were no triple- or quadruple-valve IE cases in our series. The most common etiologic micro-organism in our series was S. aureus (43%), which was responsible for multi-valvular endocarditis in three patients in each group. Staphylococci, which account for at least 30% of episodes of native valve IE, are reported to be the most important cause in IE associated with intravenous drug use (one case in our series) and in nosocomial IE [9]. Staphyloccocus aureus is able to infect previously normal heart valves (four patients in our series) and usually causes an acute illness [9]. All of our strains of S. aureus were methicillin sensitive. The second most common micro-organisms in our patients with multi-valvular endocarditis were viridans streptococci (36%), which included S. mitis, S. sanguis, and S. mutans. Since the 1960s, the percentage of cases caused by viridans streptococci has decreased to about 35% [10]. Two patients (14%) in our series had enterococci as the etiologic agent. Enterococci normally inhabit the gastrointestinal and genitourinary tracts and are the cause in 5–10% of patients with IE [11]. One patient (7%) in our series had polymicrobial IE. This patient had no known predisposing factors, but presented with aortic- and tricuspid-valve infection by S. aureus and K. pneumoniae. Antibiotic therapy consisted of an anti-staphylococcal cephalosporin plus an aminoglycoside until the patient expired from internal haemorrhage from disseminated intravascular coagulation. Although there are reports that suggest that patients with either infection of the aortic valve or infection of two or more
© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212
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Table 4 Complications of uni-valvular and multi-valvular endocarditis
Complications
Uni-valvular endocarditis (n = 25)
Multi-valvular endocarditis (n = 14)
Statistical significance
Congestive heart failure Acute renal failure Cerebrovascular accident Valve replacement surgery Death
4 (16%) 4 (16%) 2 (8%) 4 (16%) 2 (18%)
9 (64%) 6 (43%) 1 (7%) 3 (21%) 3 (21%)
statistically significant (P ³ 0.002)a not significant not significant not significant not significant
Four patients in the uni-valvular and six patients in the multi-valvular endocarditis group had more than one complication. a Chi square method.
valves are more likely to die or require early operation for management of complications [7], the mortality rate in our series was 21% (three patients), which is comparable with our single-valve IE cases (18%). (Table 4). Fifty percent of the patients (seven patients) were discharged after successful medical management alone and 29% (four patients), underwent valve replacement. The most common complications in our series were congestive heart failure (64%) and acute renal failure (50%). Occurrence of embolic events (i.e. pulmonary embolism, cerebral vascular accident, disseminated intravascular coagulation, etc.) and splenic abscess/infarct were each 21%. Among the complications, only congestive heart failure was statistically more common in the multi-valvular versus the uni-valvular group. In conclusion, the incidence of multi-valvular endocarditis occurred in 18% of our series of IE, with involvement of mitral and aortic valves being most common. Only congestive heart failure was found to be statistically more common in multivalvular than uni-valvular endocarditis. REFERENCES 1. Rippe JM, Curley F, Paraskos JA, Schoen FJ, Cohn LH, Alpert JS. Triple-valve endocarditis with unusual echocardiographic findings.
Am Heart J 1984; 107: 598–605. 2. Deonarine B, Lazar J, Gill MV, Cunha BA. Quadri-valvular endocarditis caused by Streptococcus mutans. Clin Microbiol Infect 1997; 3: 139–41. 3. Henderson RA, Palmer TJ. Echocardiographic diagnosis of infective endocarditis of all four cardiac valves. Int J Cardiol 1991; 33: 173–5. 4. Hobbs RD, Downing SE, Andriole VT. Four-valve polymicrobial endocarditis caused by Pseudomonas aeruginosa and Serratia marcescens. Am J Med 1982; 72: 164–8. 5. Farrer W. Four-valve endocarditis caused by Corynebacterium CDC Group I1. South Med J 1987; 80: 923–5. 6. Kong R, Mebazaa A, Heitz B et al. Case of triple endocarditis caused by Rothia dentocariosa and results of a survey in France. J Clin Micro 1998; 36: 309–10. 7. Chambers HF, Korzeniowski OM, Sande MA. Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine 1983; 62: 170–7. 8. Durack DT, Lukes AS, Bright DR et al. New criteria for the diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994; 96: 200–9. 9. Lazar JM, Smith RH. Echocardiographic detection of vegetations in infective endocarditis. Infect Dis Pract 1996; 20: 38–9. 10. Saccente M, Cobbs CG. Clinical approach to infective endocarditis. Cardiol Clin 1996; 14: 351–62. 11. Weinstein L, Brusch JL. Infective endocarditis. New York: Oxford University Press, 1996.
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Multi-valvular endocarditis N. Kim1, J. M. Lazar2, B. A. Cunha1, W. Liao2 and V. Minnaganti1 1
Infectious Disease Division and the 2Division of Cardiology, Winthrop-University Hospital, Mineola, New York
Objective Seventy-seven cases of native valve infective endocarditis as determined by the Duke criteria, were
reviewed to determine the incidence and clinical features of multi-valvular endocarditis. Methods Fourteen of 77 patients (18%) had multi-valvular endocarditis most commonly involving the mitral
and aortic valves. Staphylococcus aureus (43%) and viridans streptococci (36%) were the most common organisms causing multi-valvular endocarditis. Results Definite or probable vegetations were found in 50% of the patients by two-dimensional transthoracic
echocardiograph and/or transesophageal echocardiograph, and possible vegetations were detected in 21%. The overall mortality in our series was 21%; 29% underwent valve replacement and 50% were treated medically. The major complications of multi-valvular endocarditis were congestive heart failure (64%), acute renal failure (50%), embolic events (21%), and splenic abscess/infarcts (21%). Conclusions Our data suggests complications of multi-valvular endocarditis, compared with uni-valvular
endocarditis are similar except for heart failure. Heart failure is statistically more common in multi-valvular endocarditis (P ¾ 0.002). Keywords multi-valvular infective endocarditis Accepted 25 November 1999
Clin Microbiol Infect 2000; 6: 207–212
INTRODUCTION Infective endocarditis (IE) involving multiple cardiac valves is uncommon. The majority of echocardiographically demonstrated endocarditis occurs on a single valve; the involvement of two valves occurs much less frequently, and triple- or quadruple-valve involvement is extremely rare [1–6]. Demonstration of multi-valvular involvement in patients with suspected IE is important. Mortality rate is more likely to be higher in patients with infection of two or more valves than a single valve and these patients might require early operation for management of complications [7]. We reviewed the medical records of 77 patients with documented IE to study the incidence, presentation, outcome, and complications of multi-valvular endocarditis. METHODS The medical records of all adult patients with documented native valve IE were reviewed. Endocarditis was defined using Corresponding author and reprint requests: B. A. Cunha, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA Tel: +1 516 663 2505 Fax: +1 516 663 2753
the Duke criteria [8]. The patients were admitted to WinthropUniversity Hospital, a 600-bed, tertiary care, teaching hospital in Mineola, New York, between August 1990 and November 1994. Of 77 patients who met the Duke criteria for IE, 14 patients had multi-valvular endocarditis on the basis that septicemia was present in a febrile patient, with or without a new or changing heart murmur, who had more than one cardiac valve involvement demonstrated by two-dimensional (2-D) transthoracic echocardiograph (TTE), or transesophageal echocardiograph (TEE) images of vegetations, or by new regurgitation detected by Doppler echocardiography. Of 14 cases of multi-valvular endocarditis reviewed, information pertaining to demographic characteristics, predisposing factors, microorganisms involved, sites of infection, clinical and laboratory features, outcome, and complications were analyzed. Twentyfive patients with uni-valvular endocarditis were selected from the remaining 63 patients as age-matched controls.
RESULTS Results are summarized in Tables 1 and 2. Of 77 IE patients reviewed, 14 patients (18%) had multiple-valve involvement. These 14 patients were divided into two groups. Group I
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Figure 1 Transesophageal echocardiographic (TEE) images showing large echodensities on the mitral valve and the aortic valve.
included seven patients with underlying heart disease (e.g. mitral valve prolapse, rheumatic heart disease, congenital/acquired valvular diseases, a history of IE, etc.). Group II included seven patients with or without other known predisposing factors (e.g. alcohol abuse, steroid use, diabetes mellitus, etc.). All 14 cases of multi-valvular endocarditis involved two valves and there was no triple- or quadruple-valve endocarditis in our series. The patients’ age range was 31–96 years (mean 65 years). The male : female ratio was 4.3, equally divided in each group. In group I, the mean age was 62 years, whereas in group II the mean age was 68 years. Predisposing factors, which were found in various combinations in 11 of these 14 patients (79%), were mitral valve prolapse (two patients; 14%), rheumatic heart disease (one patient; 7%), congenital valvular disease–mitral stenosis (one patient; 7%), acquired valvular disease– aortic insufficiency (one patient; 7%), a history of IE (two patients; 14%), recent permanent pacemaker placement (one patient; 7%), recent dental procedure (two patients; 14%), recent abdominal surgery (one patient; 7%), intravenous drug abuse (one patient; 7%), alcohol abuse (one patient; 7%), steroid use (one patient; 7%), and diabetes mellitus (two patients; 14%). The etiologic micro-organisms found in these 14 patients were Staphylococcus aureus in six patients (43%)—three patients in each group; viridans streptococci (e.g. Streptococcus mutans, Streptococcus sanguis, and Streptococcus mitis) in five patients (36%)— three patients in group I and two patients in group II; and enterococci in two patients (14%)—one patient in each group. One patient in group II had two micro-organisms, Staphylococcus aureus and Klebsiella pneumoniae. This patient was treated with an anti-staphylococcal cephalosporin and an aminoglycoside, but unfortunately died. The valves most frequently involved were mitral and aortic valves (12 of 14 patients; 86%)—six patients in each group.
Mitral and tricuspid valves were involved in one patient in group I, and the aortic and tricuspid valves were involved in one patient in group II. We had no methicillin-resistant strains among patients infected with S. aureus in our series. All patients underwent 2-D TTE and Doppler echocardiography and some patients underwent TEE when necessary (Figure 1). We had no methicillin-resistant strains among patients infected with S. aureus. Definite or probable vegetations were found in seven of the patients (50%)—five patients in group I and two patients in group II, and possible vegetations were found in a further three of the 14 patients (21%)—one patient in group I and two patients in group II. All patients demonstrated on the Doppler echocardiogram mild to moderate regurgitation of affected valves. Clinically, a new or changing murmur was detected in seven of the 14 patients (50%)— two patients in group I and five patients in group II. Osler’s nodes, Janeway lesions, splinter haemorrhages, or petechiae were not, or rarely (in one to two patients), detected in the majority of our patients. Thirteen of 14 patients (93%) presented with fever (temperature ×100.6 °F, 38 °C) and chills. Among them, three patients (23%), all in group I, had temperatures ×102 °F (38.8 °C). Microscopic haematuria was a common finding (10 of 14 patients; 71%)—five patients in each group. Erythrocyte sedimentation rate (ESR) was elevated in all patients (100%) with a range of 26–108 mm/h. Two of 14 patients (14%), both in group II, had ESR × 100 mm/h. The overall mortality in our series was 21% (three of 14 patients)—one patient in group I and two patients in group II. Four of 14 patients (29%) underwent surgical intervention (multiple valve replacement or pacemaker replacement)—three patients in group I and one patient in group II. Seven of 14 patients (50%) were discharged after prolonged antibiotic therapy—three patients in group I and four patients in group II. The major complications among these 14 patients, in various combinations, were congestive heart failure (nine patients; 64%), acute renal failure (seven patients; 50%), embolic events (i.e. pulmonary emboli (PE), cerebral vascular accidents, disseminated intravascular coagulation, etc.) (three patients; 21%), splenic abscess or infarct (three patients; 21%), persistent bacteremia (two patients; 14%), meningitis (one patient; 7%), and liver necrosis (one patient; 7%). (Tables 1, 2) The characteristics of the uni-valvular control group are shown in Table 3. With the exception of congestive heart failure, the complications of multi-valvular and uni-valvular endocarditis were similar and not statistically different. Complications included acute renal failure, cerebral vascular accident, and congestive heart failure, and were not statistically different in patients with multi- or uni-valvular endocarditis. Congestive heart failure was a more frequent complication in the multi-valvular group, which was statistically different (P ¾ 0.002). The valve replacement surgery and mortality were not significantly different in both groups. (Table 4).
© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212
Aortic insufficiency RHD IVDU, h/o endocarditis Congenital MS h/o endocarditis MVP MVP, dental work 2 days PTA p.p.m. 2 months PTA
None
Steroid use None Recent tooth extraction None Recent abdominal surgery None
77 M 61 M 31 F 37 M
63 M
69 F 96 F 36 M 80 M 75 F 55 M
© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212 S. aureus (MSSA) S. aureus (MSSA) S. sanguis S. mitis Enterococci S. aureus (MSSA) K. pneumoniae
S. aureus (MSSA)
Enterococci
S. mutans S. viridans
S. aureus (MSSA) S. aureus (MSSA) S. aureus (MSSA) S. mutans
Micro-organism
MV,AV MV,AV MV,AV MV,AV MV,AV AV,TV
MV,AV
MV,AV
MV,AV MV,AV
MV,AV MV,AV MV,AV MV,AV
Valve
No No Yes No Probable Possible
Possible
Yes
Possible Yes
No Yes Yes Yes
Veg by echo
Yes Yes Yes No No Yes
Yes
Yes
No Yes
No No No No
New murmur
Yes No Yes No Yes Yes
Yes
Yes
Yes Yes
Yes Yes Yes Yes
Fever
15.1 7.4 12.2 11.5 11.9 13.1
10.5
14.9
8.2 8.7
13.3 8.8 6.9 10
WBC
79 29 64 26 108 108
46
90
37 83
53 53 79 99
ESR
Discharge Discharge MVR, AVR/discharge Discharge Discharge Death
p.p.m. replacement/ discharge Death
Discharge Discharge
Death MVR,AVR/discharge Discharge MVR,AVR/discharge
Outcome
CVA,meningitis, CHF, ARF, bacteremia, splenic infarct CHF CHF, ARF None None CHF CHF,ARF, liver necrosis, splenic infarct, DIC
CHF, ARF
None ARF
CHF, ARF, bacteremia, splenic infarct CHF PE, pancytopenia CHF
Complications
ARF, acute renal failure; AVR, aortic valve replacement; CHF, congestive heart failure; CVA, cerebral vascular accident; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; ESR, erythrocyte sedimentation rate; IVDU, intravenous drug user; MSSA, methicillin-sensitive Staphylococcus aureus; MS, mitral stenosis; MVP, mitral valve prolapse; MVR, mitral valve replacement; PTA, prior to admission; PE, pulmonary embolism; p.p.m, permanent pacemaker; RHD, rheumatic heart disease; WBC, white blood cell count; MV, mitral valve; TV, tricuspid valve; AV, aortic valve.
69 F
79 M 78 F
Predisposing factors
Age/Sex
Table 1 Multi-valvular endocarditis
Kim et al Multi-valvular endocarditis
209
Aortic Regurgitation Heart murmur None None RHD, dental work, 2 weeks PTA MVR Rheumatic fever, dental work 1 month PTA None None None MVP, mitral regurgitation MVP None None
None None, dental work 6 months PTA None Dental work 8 weeks PTA MVR
Past h/o endocarditis IVDA, endocarditis None MVP, endocarditis Dental work 1 month PTA AVR
42 M 36 M 62 F 49 F 80 F 64 F 67 M 74 M 81 F 71 F 81 F 38 M 58 F 83 F
42 M 51 M 38 M 25 M 68 F
36 F 44 M 36 M 61 F 44 M 68 M
S. viridans S. viridans S. sanguis S. sanguis S. viridans S. epidermidis (MSSE)
S. viridans S. viridans S. aureus (MSSA) S. sanguis S. viridans
S. mitis S. morbilorum S. defectivus S. sanguis S. viridans S. intermedius S. salivarius S. viridans S. viridans S. viridans S. constellatus S. viridans S. sanguis S. aureus (MSSA)
Micro-organism
VSD AV AV MV AV MV
MV MV TV AV MV
AV MV MV MV NA MV MV MV NA MV MV MV AV MV
Valve
NA Possible Yes Possible Possible No
No Yes Yes Yes Yes
Yes Yes Yes Yes No No Yes No Not done No No Possible Yes Yes
Veg by echo
No No No No Yes No
No No No Yes No
No No Yes No No No Yes No No No No No Yes Yes
New murmur
No Yes Yes Yes Yes Yes
Yes Yes No No Yes
Yes Yes Yes Yes Yes No Yes Yes Yes No No Yes No Yes
Fever
6.8 11.8 13.2 15.4 11.6 7.2
17.7 11.4 6.8 10.9 11.6
10.3 9.7 12.4 10.5 17.9 7.7 14 13.5 17.5 9.4 8.6 11.5 9.1 11.2
WBC
24 37 63 71 NA 14
NA 81 131 75 107
50 65 106 121 71 79 84 36 113 62 49 83 116 108
ESR
Discharge Discharge AVR/discharge Discharge Discharge Discharge
Discharge Discharge Discharge Discharge Discharge
Discharge Discharge Discharge Discharge Discharge Discharge MVR/discharge Discharge Death Discharge Discharge Discharge AVR/discharge MVR/death
Outcome
None ARF, renal abscess None None None None CHF None CVA, MI, CHF, ARF None None None CHF CHF, ARF, pulmonary oedema None CVA None None Osteomyelitis, T10–11, ARF None None NA None None None
Complications
ARF, acute renal failure; AVR, aortic valve replacement; CHF, congestive heart failure; CVA, cerebral vascular accident; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; ESR, erythrocyte sedimentation rate; MSSA, methicillin-sensitive Staphylococcus aureus; MS, mitral stenosis; MVP, mitral valve prolapse; MVR, mitral valve replacement; PTA. prior to admission; PE, pulmonary embolism; p.p.m., permanent pacemaker; RHD, rheumatic heart disease; WBC, white blood cell count; MV, mitral valve; TV, tricuspid valve; AV, aortic valve.
Predisposing factors
Age/Sex
Table 2 Valvular endocarditis (comparative group)
210 Clinical Microbiology and Infection, Volume 6 Number 4, April 2000
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Kim et al Multi-valvular endocarditis
Table 3 Multi-valvular endocarditis in the WinthropUniversity Hospital case series: controls/complications Number of patients = 14 Mean age (range) = 65 (31–96) years Male : female ratio = 8 : 6 Predisposing factors = 11/14 patients (79%) Mitral valve prolapse = 2/14 patients (14%) Rheumatic heart disease = 1/14 patients (7%) Congenital valvular disease (mitral stenosis) = 1/14 patients (7%) Acquired valvular disease (aortic insufficiency) = 1/14 patients (7%) History of infective endocarditis = 2/14 patients (14%) Recent permanent pacemaker placement = 1/14 patients (7%) Recent dental procedure = 2/14 patients (14%) Recent abdominal surgery = 1/14 patients (7%) Intravenous drug abuse = 1/14 patients (7%) Etiologic micro-organisms Staphylococcus aureus (MSSA) = 6/14 patients (43%) Viridans streptococci (Streptococcus mutans, S. sanguis, and S. mitis) = 5/14 patients (36%) Enterococci = 2/14 patients (14%) Staphylococcus aureus and Klebsiella pneumoniae (7%) Sites of infection Mitral valve and aortic valve = 12/14 patients (86%) Mitral valve and tricuspid valve = 1/14 patients (7%) Aortic valve and tricuspid valve = 1/14 patients (7%) Echocardiogram Definite/probable vegetation = 7/14 patients (50%) Possible vegetation = 3/14 patients (21%) No vegetation = 4/14 patients (29%) Clinical and laboratory features New or changing murmur = 7/14 patients (50%) Osler’s nodes = 0/14 patients (0%) Janeway lesions = 1/14 patients (7%) Splinter hemorrhages = 0/14 patients (0%) Petechiae = 2/14 patients (14%) Fever (T × 100.6 °F) = 13/14 patients (93%) (T × 102 °F) = 3/13 patients (23%) Chills = 13/14 patients (93%) Microscopic hematuria = 10/14 patients (71%) Elevated ESR (×20 mm/h) = 14/14 patients (100%) ESR range = 26–108 mm/h (ESR × 100 mm/h = 2/14 patients (14%)) Outcome and complications Death = 3/14 patients (21%) Surgical intervention (multi-valve replacement) = 4/14 patients (29%) Congestive heart failure = 9/14 patients (64%) Acute renal failure = 7/14 patients (50%) Embolic events = 3/14 patients (21%) Splenic abscess/infarct = 3/14 patients (21%) Persistent bacteremia = 2/14 patients (14%) Meningitis = 1/14 patients (7%) Liver necrosis = 1/14 patients (7%) ESR, erythrocyte sedimentation rate.
211
Post-mortem results were not obtained on any patient. Pathology following valve replacement was available in three patients with multi-valvular endocarditis and four patients in the uni-valvular group. Pathology reports were similar in both groups and were reported as having acute organizing inflammation, fibrin and calcium deposition associated with vascular and fibroblastic proliferation on the removed valve leaflets. All removed valve cells were negative for bacterial growth. DISCUSSION The occurrence of multi-valvular endocarditis is uncommon. The majority of IE cases involves a single valve, and demonstration of two-, triple-, or even quadruple-valve involvement by echocardiography is less frequent [1–6]. We reviewed the medical records of patients who were admitted to our hospital over a 4-year period with documented IE to determine the incidence and presentation of multi-valvular endocarditis using the Duke criteria [8]. We report here that among 77 patients with documented IE reviewed, there were 14 patients (18%) who had multi-valvular endocarditis, and 63 with uni-valvular endocarditis. Twenty-five age matched patients with uni-valvular endocarditis were selected as age-matched controls. Fourteen patients had two-valve involvement demonstrated by echocardiography and there were no triple- or quadruple-valve IE cases in our series. The most common etiologic micro-organism in our series was S. aureus (43%), which was responsible for multi-valvular endocarditis in three patients in each group. Staphylococci, which account for at least 30% of episodes of native valve IE, are reported to be the most important cause in IE associated with intravenous drug use (one case in our series) and in nosocomial IE [9]. Staphyloccocus aureus is able to infect previously normal heart valves (four patients in our series) and usually causes an acute illness [9]. All of our strains of S. aureus were methicillin sensitive. The second most common micro-organisms in our patients with multi-valvular endocarditis were viridans streptococci (36%), which included S. mitis, S. sanguis, and S. mutans. Since the 1960s, the percentage of cases caused by viridans streptococci has decreased to about 35% [10]. Two patients (14%) in our series had enterococci as the etiologic agent. Enterococci normally inhabit the gastrointestinal and genitourinary tracts and are the cause in 5–10% of patients with IE [11]. One patient (7%) in our series had polymicrobial IE. This patient had no known predisposing factors, but presented with aortic- and tricuspid-valve infection by S. aureus and K. pneumoniae. Antibiotic therapy consisted of an anti-staphylococcal cephalosporin plus an aminoglycoside until the patient expired from internal haemorrhage from disseminated intravascular coagulation. Although there are reports that suggest that patients with either infection of the aortic valve or infection of two or more
© 2000 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 6, 207–212
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Clinical Microbiology and Infection, Volume 6 Number 4, April 2000
Table 4 Complications of uni-valvular and multi-valvular endocarditis
Complications
Uni-valvular endocarditis (n = 25)
Multi-valvular endocarditis (n = 14)
Statistical significance
Congestive heart failure Acute renal failure Cerebrovascular accident Valve replacement surgery Death
4 (16%) 4 (16%) 2 (8%) 4 (16%) 2 (18%)
9 (64%) 6 (43%) 1 (7%) 3 (21%) 3 (21%)
statistically significant (P ³ 0.002)a not significant not significant not significant not significant
Four patients in the uni-valvular and six patients in the multi-valvular endocarditis group had more than one complication. a Chi square method.
valves are more likely to die or require early operation for management of complications [7], the mortality rate in our series was 21% (three patients), which is comparable with our single-valve IE cases (18%). (Table 4). Fifty percent of the patients (seven patients) were discharged after successful medical management alone and 29% (four patients), underwent valve replacement. The most common complications in our series were congestive heart failure (64%) and acute renal failure (50%). Occurrence of embolic events (i.e. pulmonary embolism, cerebral vascular accident, disseminated intravascular coagulation, etc.) and splenic abscess/infarct were each 21%. Among the complications, only congestive heart failure was statistically more common in the multi-valvular versus the uni-valvular group. In conclusion, the incidence of multi-valvular endocarditis occurred in 18% of our series of IE, with involvement of mitral and aortic valves being most common. Only congestive heart failure was found to be statistically more common in multivalvular than uni-valvular endocarditis. REFERENCES 1. Rippe JM, Curley F, Paraskos JA, Schoen FJ, Cohn LH, Alpert JS. Triple-valve endocarditis with unusual echocardiographic findings.
Am Heart J 1984; 107: 598–605. 2. Deonarine B, Lazar J, Gill MV, Cunha BA. Quadri-valvular endocarditis caused by Streptococcus mutans. Clin Microbiol Infect 1997; 3: 139–41. 3. Henderson RA, Palmer TJ. Echocardiographic diagnosis of infective endocarditis of all four cardiac valves. Int J Cardiol 1991; 33: 173–5. 4. Hobbs RD, Downing SE, Andriole VT. Four-valve polymicrobial endocarditis caused by Pseudomonas aeruginosa and Serratia marcescens. Am J Med 1982; 72: 164–8. 5. Farrer W. Four-valve endocarditis caused by Corynebacterium CDC Group I1. South Med J 1987; 80: 923–5. 6. Kong R, Mebazaa A, Heitz B et al. Case of triple endocarditis caused by Rothia dentocariosa and results of a survey in France. J Clin Micro 1998; 36: 309–10. 7. Chambers HF, Korzeniowski OM, Sande MA. Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine 1983; 62: 170–7. 8. Durack DT, Lukes AS, Bright DR et al. New criteria for the diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994; 96: 200–9. 9. Lazar JM, Smith RH. Echocardiographic detection of vegetations in infective endocarditis. Infect Dis Pract 1996; 20: 38–9. 10. Saccente M, Cobbs CG. Clinical approach to infective endocarditis. Cardiol Clin 1996; 14: 351–62. 11. Weinstein L, Brusch JL. Infective endocarditis. New York: Oxford University Press, 1996.
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