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Prosthetic valve endocarditis
Surgery for Acquired Heart Disease
Prosthetic valve endocarditis Experience with porcine bioprostheses Prosthetic valve endocarditis remains an infrequent but serious complication of cardiac valvular replacement. Prosthetic valve endocarditis was diagnosed in 56 (1.8 %) of 3200 patients in whom one or more porcine bioprostheses were implanted between 1975 and 1988. Of the 56 patients with prosthetic valveendocarditis, there were 40 men and 16 women, with a mean age at initial implantation of 57 years (27 to 81 years). Of the 56 patients, 6 were initiaUy treated for native valve endocarditis. There were 8 cases of early prosthetic valve endocarditis (defined as occurring less than 60 days after initial surgical intervention) and 48 cases of late prosthetic valve endocarditis (occurring after 60 days). The overaU mortality rate of the 56 patients was 32 % (18 patients). Of the 8 patients with early prosthetic valve endocarditis, 6 (75 %) died. Of the 48 patients with late prosthetic valve endocarditis, 12 (25 %) died. The predominant organisms were Staphylococcus epidermidis (12 cases), Streptococcus viridans (8 cases) and Staphylococcus aureus (7 cases). The presence of hemodynamic compromise, including congestive heart failure, septic embolism, persistent sepsis, and echocardiographic evidence of vegetations, dictated the mode and timing of the addition of surgical intervention to medical therapy. The survival rate for medically and surgicaUy treated patients with late prosthetic valve endocarditis was 91 % (20 patients); none of the patients with early prosthetic valve endocarditis survived (aU had severe hemodynamic compromise). We analyzed 18 factors for the prediction of early and late death. The predictors of death by univariate analysis for both early and late prosthetic valve endocarditis were age, diagnosis time, renal status, sepsis, management mode, fever, dental procedures, and dental prophylaxis. The predictors by multivariate analysis were age, diagnosis time, renal status, and management mode for early prosthetic valve endocarditis, and only diagnosis time for late prosthetic valve endocarditis. Annular abscess formation occurred in 27 % of the patients. There were no complex aortic or mitral reconstructions. There was one reoperation for recurrent and residual endocarditis. There was one late death as a result of recurrent prosthetic valve endocarditis. We advocate early diagnosis and aggressive combined medical and surgical treatment before the development of hemodynamic compromise and other characteristic signs when the culprit organisms are Staphylococcus aureus, gram-negative organisms, and Candida albicans. (J THORAe CARDIOVASC SURG 1993;105: 428-34)
S. S. Sett, MD,a M. P. J. Hudon, MSc,a W. R. E. Jamieson, MD,a and A. W. Chow, MD,b Vancouver, British Columbia, Canada
From the Department of Surgery, Division of Cardiovascular and Thoracic Surgery; and the Department of Medicine, Division of Infectious Diseases," University of British Columbia, Vancouver General Hospital, Vancouver, Canada.
Address for reprints: W. R. E. Jamieson, MD, Division of Cardiovascular and Thoracic Surgery, Department of Surgery, University of British Columbia, 3100-910 West 10th Ave., Vancouver, B.c. Canada V5Z 4E3.
Read at the Sixteenth Annual Meeting of The Western Thoracic Surgical Association, Coronado, Calif., June 20-23, 1990.
0022-5223/93 $1.00 +.10
428
Copyright
Cc)
1993 by Mosby-Year Book, Inc. 12/6/41884
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 3
Prosthetic valve endocarditis (PVE) remains a feared complication ofvalve replacement, even in the modern era of antimicrobial therapy. The overall occurrence of PVE is in the range of 2% to 4%.1 From 1975 to 1988, we studied clinical courses and outcomes for patients who had PVE. 2-8 Both the Hancock standard (Medtronic Cardiopulmonary Division, Minneapolis, Minn.) and the Carpentier-Edwards standard porcine bioprostheses (Baxter Healthcare Corp., Edwards Div., Irvine, Calif.) were introduced at our center in 1975,2-7 and the Carpentier-Edwards supraannular prosthesis was introduced in 1982.8 The purpose of this retrospective review was to identify those factors that influence survival in a population with PVE restricted to porcine bioprostheses. Patients and methods The patient population was determined by a retrospective review of patients who had endocarditis related to porcine bioprostheses between 1975 and 1988. A total of 3200 patients underwent implantation of porcine bioprostheses during this period.These patients had the Hancock standard, the Carpentier-Edwards standard, or the Carpentier-Edwards supraannular prosthesisimplanted in aortic, mitral, or multiple positions. Patients who had undergone concomitant procedures, such as coronary artery bypass, were included. There were no dramatic changes in operative technique throughout the period of review. The majority of valves were implanted by means of interrupted sutures with strips of Teflon fluorcarbon resins or pledgets; some were implanted by means of continuous monofilament sutures. All patients received prophylactic antibiotic coverage in the perioperative period. Current practices include the use of a cephalosporinor vancomycin hydrochlorideand an aminoglycosidein the perioperative period,extended t048 hours postoperativelyor until all central lines are removed. Follow-up of survivorswas obtained through the valve registry at the University of British Columbia. Definitions. The diagnosis of PYE was based on the following":(I) two blood cultures positivefor the same organism in a patient with a compatible clinical syndrome that consisted of fever, new cardiac murmurs, splenomegaly, petechiae, Roth's spots, Osler's nodes, or Janeway's lesions and (2) histopathologicevidenceof endocarditis in a surgical or autopsy specimen. Endocarditis that was diagnosed within 60 days of operation wasclassified as early postoperativeendocarditis, whereas those cases that occurred after 60 days were classified as late.l? Data analysis. We analyzed 18 variables as predictors of early and late mortality: (I) age, (2) sex, (3) history of drug abuse, (4) type of valve implanted (Carpentier-Edwards standard, Carpentier-Edwards supra-annular, or Hancock standard), (5) valve position (aortic, mitral, tricuspid, or combination thereof), (6) time to diagnosis, defined as the time from onset of symptoms to the first hospital admission because of PYE, (7) renal status with renal insufficiency indicated by a sustained increase in serum creatinine, (8) presence of ongoing sepsis, definedas persistent elevationof white blood count com-
Sett et al.
429
Table I. Distribution of PVE patient population (n = 56) by valve position and deaths
Totals
Valve position
Early PVE
Late PVE
AVR MYR MR 8
4 (3) 3 (2) I (I) 8 (6)
23 (7) 17 (4) 8 (I) 48 (12)
PVE, Prosthetic valve endocarditis; AVR, aortic valve replacement; MVR, mitral valve replacement; MR, multiple valve replacement; ( ), denotes deaths.
bined with compatible clinical picture, (9) type of organism, (10) presenceof conduction abnormality, (I I) New York Heart Association classification, (12) history of embolic event, (13) mode of management (either medical or combined medical and surgical therapy), (14) specificantibiotic used, (15) presence of fever, (16) dental procedure before episode of PYE, (17) no history of dental prophylaxis, (18) history of native valve endocarditis (NYE). Statistical methods. Univariate analysis was performed with Student's t test and the X2 test to assess all relationships of the independent variables to the outcome, the dependent variable. Multivariate analysis was performed with a stepwise or Cox logistic regression analysis with the outcome as the dependent variable. Both groups, early and late PYE death, were evaluated. Results PVE was diagnosed in 56 (1.8%) of 3200 patients who had one or more porcine bioprostheses implanted between 1975 and 1988, In 42 patients PVE was diagnosed on the basis of two or more positive blood cultures and a clinical syndrome that was compatible with endocarditis, whereas 30 patients had histopathologic evidence of PVE at the time of surgical intervention or autopsy. The distribution of the 56 patients by valve position and classification of PVE is shown in Table I. The mean age at initial surgical intervention was 57 years, with a range of 27 to 81 years. Six patients (10.6%) had undergone valve replacement previously for NVE. There were 8 cases of early PVE that occurred at a mean of 26.1 ± 21.9 days after surgical intervention and 48 cases of late PVE that occurred at a mean of 38.4 ± 32.5 months, The predominant number of cases of PVE occurred in the aortic position (27 of 56 patients). Twenty patients had endocarditis involving a mitral prosthesis, and nine had endocarditis involving multiple valve replacements (Table I). The overall mortality rate for the 56 patients with PVE was 32% (18/56). The mortality rate was 75% (6/8) in the early PVE group and 25% (12/48) in the late PVE group. The most common organisms were Staphylococcus
The Journal of Thoracic and Cardiovascular Surgery March 1993
4 3 0 Sett et al.
Table II. Distribution ofpathologic organism by time of onset of PVE and deaths Organism Staphyloccus aureus Staphylococcus epidermidis Streptococcus viridans Hemolytic Streptococcus Enterococcus Diphtheroids Pseudomonas aeruginosa Serratia marcescens Candida albicans Klebsiella pneumonia Actinomycetes actinomycetocomittans Culture negative Multiple Total
0, Denotes
Fig. 1. Mode of treatment (medical and surgical).
epidermidis, then Streptococcus viridans and Staphylococcus aureus (Table II). Eleven patients had cultures that tested negative for endocarditis. Two patients with early PYE caused by Staphylococcus epidermidis were treated medically and survived (Table II). There were seven patients with Staphylococcus aureus PYE. Four of these survived and three died. Three of four survivors underwent combined medical/surgical therapy. The three patients who did not survive had undergone medical treatment alone. Gram-negative organisms predominated in the early PYE group (Table II). All of these patients died. There were four patients with PYE that was caused by Candida albicans; two survived and two died. One patient who had candidal septicemia after double valve replacement of the aortic and mitral valves underwent combined medical treatment and double valve rereplacement and survived. The other survivor with late candidal PYE had both valves replaced as well. One patient with candidal PYE involving a mitral prosthesis died while receiving medical treatment, and the final patient, who had undergone replacement of aortic and mitral valves, died of candidal septicemia with multiorgan failure after combined medical/surgical therapy.
Early PVE I
(I)
2 (-)
Late PVE 6 (2) 10 (4) 8 (2) 1(-)
(I) (I) (I) (I) (I)
2 (-) 1(-) 1(-)
3
(I)
4
(I)
II (2) 1(-) 48 (12)
deaths.
Causes of death in patients who experienced early PYE were septicemia, congestive heart failure, and thrombotic occlusion of a mitral prosthesis (in one patient). The causes of death in patients with late PYE were congestive heart failure, hepatic and renal failure, septicemia, ruptured mycotic aneurysm, and adult respiratory distress syndrome. These occurred singly or in combination. Ofsix patients with previous NYE, early PYE occurred in one and late PYE occurred in five. The patient who had early PYE died of Pseudomonas septicemia; the original NYE organism was Staphylococcus aureus. One patient in the late PYE group had Candida albicans septicemia after double valve replacement for NYE, which was caused by Staphylococcus epidermidis. The case was mentioned in the preceding paragraph. The patient in the late PYE group who died had a history of chronic intravenous drug abuse and had undergone mitral and tricuspid valve replacement. In only one patient in the late PYE group was Streptococcus viridans the original organism in NYE. The others were dissimilar or had negative cultures. Figs. 1 and 2 illustrate the outcomes after both medical treatment alone and combined medical and surgical treatment in early and late PYE, respectively. After medical treatment, two patients survived early PYE. However, 91 % of the patients with late PYE survived after combined medical and surgical therapy whereas 62% of those who had medical therapy alone survived (p < 0.01). Fig. 3 denotes the numbers of patients who were found to have annular abscesses, dehiscence, vegetations, and
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 3
Sett et al.
43 I
Perforation
Vegetations
Dehiscence
AnnularAbscess
w
~
~
~
~
00
M
00
00
100
26 Reoperated Cases
Fig. 3. Findings at reoperation.
Only time to diagnosis was found to be a predictor of late mortality after multivariate analysis. Follow-up was completed in all patients, and there was one subsequent death that was related to recurrent PVE. This patient had an upper gastrointestinal tract hemorrhage and Staphylococcus epidermidis septicemia and died after cardiac arrest. Autopsy confirmed a chronic annular abscess around the aortic prosthesis. Fig. 2. Mode of treatment (medical).
perforations. Only 27% (7/26) of the patients who had undergone a second operation had annular abscesses. Of the seven patients in whom annular abscesses formed, five had undergone previous aortic valve replacement and two had undergone multiple valve replacement. Dehiscence was the dominant finding in 42% (11/26) of patients with reoperation. The other findings were vegetations in 35% (9/26) and leaflet perforations in 31% (8/26). There were no complex aortic root or mitral procedures in this series. Eighteen variables listed in Table III were used for univariate and multivariate analyses in the determination of predictors of death in both early and late PVE. In both the early and late groups, univariate analysis revealed that renal status (renal insufficiency that was indicated by a sustained rise in serum creatinine level), presence of ongoing sepsis, mode of treatment, presence of fever, previousdental procedure, lack of dental prophylaxis, time to diagnosis (defined as the time from the onset of symptoms to the first hospital admission), and age of patient if over 65 were predictors of death (p < 0.05). However, multivariate analysis revealed that renal status (p < 0.05), mode of treatment (p < 0.05), time to diagnosis (p < 0.04), and age (p < 0.05) were predictors of early death. Renal status was the strongest predictive factor.
Discussion Mortality rates that are associated with PVE have been improving since it was realized that the indications for surgical intervention should be liberalized and should not be reserved for only those patients who have severe congestive heart failure, valvular dysfunction, or multiple septic emboli or who have undergone a prolonged course of antibiotic therapy. 11-20 Even with early surgical intervention, mortality rates remain high and range from 23% to 69% in those patients with PVE, both mechanical and heterograft.': 11-13, 15. 18,20 Specifically, early PVE can be considered more precarious, with mortality rates that range from 43% to 100%.1.11-13,17,18 Mortality rates are lower in late PVE and range from 21% to 67%.1, II, 12, 16, 18 Infections in tissue valves tend to occur in the fibrin layer that covers the cusps rather than in the valve ring; infection that occurs in the latter area may subsequently form an annular abscess, although these still may occur in other areas.i" Vegetations may also form on the leaflet surface and lead to destruction or stenosis.!" The occurrence of valve ring abscess in a study that included primarily mechanical valves/" ranged from 50% to 75%; because of this complication, medical therapy alone was not successful. Extensive abscess formation may also necessitate the use of major reconstructive procedures for repair of the aortic rootl': 21, 22 or reconstruction of the mitral valve anulus.l'
The Journal of Thoracic and Cardiovascular Surgery March 1993
4 3 2 Sett et al.
Table III. Analysis offactors associated with mortality by time ofonset of PVE Analysis: Early PVE (late PVE) Variable Age Sex Drug abuse Valve type Valve position Diagnosis time Renal status Sepsis Organism Conduction abnormality NYHA class Embolism ~anagementmode
Antibiotic Fever Dental procedures Dental prophylaxis Native valve endocarditis Current status
Univariate*
p Value
x (X)
p < 0.05 (p < 0.05)
X
p<0.05
X (X) X (X) X (X)
p < 0.05 (p < 0.05) P < 0.05 (p < 0.05) P < 0.05 (p < 0.05)
X (X) X
p
X (X)
p
X
p<0.05
X (X) X (X) X (X)
p < 0.05 (p < 0.05) P < 0.05 (p < 0.05) P < 0.05 (p < 0.05)
< 0.05 (p < 0.05)
p Value
Multivariatet
< 0.04 (p < Om)
p<0.007
PVE, Prosthetic valve endocarditis; NYHA, New York Heart Association. 'Student's t test and x2 test
tStepwise or Cox logistic regression analysis
No complex reconstructions were performed in this series. None of the patients who underwent a second operation had postoperative valvular dehiscence. The absence of complex reconstructive procedures may be related to the exclusion of mechanical prostheses and the annular abscess formations that almost inevitably accompany them. There was only one instance of a conduction abnormality in this series; surprisingly enough, this was successfully treated with antibiotics and a permanent pacemaker. Conduction system abnormalities are usually associated with annular abscess formation and thus require operative intervention. Emboli were infrequently seen. Conduction abnormalities and emboli were less prevalent than indicated in recent reports.': 16 Renal dysfunction was found to be the strongest predictor of death as a result of early PYE, as seen with multivariate analysis. Baumgartner and colleagues I have also found renal dysfunction to be the most powerful predictor, and this may reflect the occurrence of ongoing congestive heart failure with low-output state and poor renal perfusion. Time to diagnosis was a significant predictor of death in both early and late PYE groups, and this partially reflects the difficulty of establishing definitive suspicion of PYE.
The definitive diagnosis can be made after the specific organism is cultured from blood; the bacteremia is continuous and should show positive results on multiple samplings in more than 99% of the cases, unless there is the presence of a fungal or rickettsial infection or the patient has had previous antibiotic therapy.-" In the present study, 11 cases of culture-negative PYE can be attributed to antibiotic therapy for suspected infection before transfer. The diagnosis of early PYE may be difficult to make; it demands a high index of suspicion and prompt initiation of bactericidal antibiotic therapy. If fever, an elevated white blood cell count, and other signs of sepsis or extracardiac infection subside and there is no persistent bacteremia, then therapy should be continued for 10 to 14 days. However, if systemic signs of toxicity persist and are accompanied by a new or changing murmur, persistent bacteremia, or both, early PYE should be suspected, echocardiography should be performed, and emergency reoperation should be considered. In this present study two survivors of early PYE underwent medical therapy alone, whereas six patients in the same group who were in the process of combined medical/surgical therapy died. Of note, in the two survivors Staphylococcus epidermidis was the culprit orga-
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 3
nism, and both patients were treated successfully with antibiotics. Although our experience is small, it is postulated that early PVE in which Staphylococcus epidermidis is the offending organism can be successfully managed with intensive medical therapy. There was a 66% mortality rate in patients with late PVE who underwent medical treatment only, compared with a 9% mortality rate in those patients who underwent combined medical/surgical therapy. Ivert and colleagues'> found that 70% of their patients died after medical treatment, but their group consisted of patients with both mechanical and tissue valves. Horstkotte and colleagues'" found that six of seven patients died after conservative therapy. It appears that prompt surgical intervention should be instituted in late PVE after the initiation of antibiotic therapy, before the development of congestive heart failure or persistent sepsis (fever, persistently elevated white blood count, shift to the left, continuous bacteremia). Results from this study suggest that all cases of PVE that are caused by Staphylococcus aureus should be treated medically and with early surgical intervention. In this series only one patient who was treated with antibiotics survived a Staphylococcus aureus PVE, which occurred in a mitral prosthesis; all others died. Furthermore, all patients with early PVE that was caused by gram-negative organisms died. Although these patients underwent combined medical/surgical therapy, the surgical intervention occurred at a time when there was marked hemodynamic compromise. It must be speculated that if surgical treatment had been instituted earlier, the outcome would have been different. Two patients survived candidal PVE after surgical treatment. Fungal PVE mandates reoperation. The only survivors of early PVE had Staphylococcus epidermidis and were treated medically. Staphylococcus epidermidis may be a unique organism, less virulent, and susceptible to eradication with medical therapy. There were three cases of recurrent endocarditis in this series (8%). One patient was undergoing medical treatment at the time of the study. One patient underwent repeat double valve replacement for Candida albicans endocarditis and was doing well at the time of this study. The additional patient was admitted with an upper gastrointestinal tract hemorrhage and Staphylococcus epidermidis septicemia. He had a cardiac arrest and died in the intensive care unit. Autopsy revealed a chronic annular abscess around the aortic prosthesis. Two series': 15 have recurrent PVE rates of 15% and 9.4%, respectively.
Sett et al.
433
The results of the present study indicate that NVE is not an incremental risk factor for the development of PVE. These findings are dissimilar to those of Ivert and colleagues.P REFERENCES I. Baumgartner WA, Miller DC, Reitz BA, et al. Surgical treatment of prosthetic valve endocarditis. Ann Thorac Surg 1983;35:87-104. 2. Jamieson WRE, Munro AI, Miyagishima RT, Allen P. Clinical evaluation of porcine heterograft cardiac valvesin 200 patients. Can J Surg 1978;21:133-5. 3. Janusz MT, Jamieson WRE, Allen P, et al. Experience with the Carpentier-Edwards porcine valve prosthesis in 700 patients. Ann Thorac Surg 1982;34:625-33. 4. Janusz MT, Jamieson WRE, Allen P, et al. Long-term follow-up of patients with porcine cardiac valve prosthesis. Can J Surg 1983;26:160-2. 5. Jamieson WRE, Pelletier LC, Janusz MT, Chaitman BP, Tyers GFO, Miyagishima RT. Evaluation of the Carpentier-Edwards porcine bioprosthesis implanted over the years. J THORAC CARDIOVASC SURG 1984;88:324-33. 6. Jamieson WRE, Tyers GFO, Gerein AN, Miyagishima RT, Munro AI, Burr LH. Carpentier-Edwards standard porcine bioprosthesis: assessment of valve-related complications. Thai J Cardiovasc Thorac Surg 1987;8: 17380.
7. Jamieson WRE. The Carpentier-Edwards standard porcine bioprosthesis: long-term results of clinical performance. L'information Cardiologique 1988;12:177-86. 8. Jamieson WRE, Tyers GFO, Munro AI, et al. CarpentierEdwards supra-annular porcine bioprosthesis: a new generation tissue valve with excellent intermediate clinical performance. J THORAC CARDIOVASC SURG 1988;96: 652-66.
9. Calderwood SB, Swinski LA, Karchmer AW, Waternaux CM, BuckleyMJ. Prosthetic valveendocarditis:analysis of factors affecting outcome of therapy. J THORAC CARDIOVASC SURG 1986;92:776-83. 10. Jones EL, Schwarzmann SW, Check WA, Hatcher CR Jr. Complications from cardiac prostheses. In: Sabiston DC, Spencer FC, eds. Surgery of the Chest ed. 4. Philadelphia: WB Saunders, 1983:1253-65. II. Masur H, Johnson WD. Prosthetic valve endocarditis. J THORAC CARDIOVASC SURG 1980;80:31-7. 12. Rossiter SJ, Stinson EB, Oyer PE, et al. Prosthetic valve endocarditis: comparison of heterograft tissue valves and mechanical valves. J THORAC CARDIOVASC SURG 1978; 76:795-803. 13. Rocchiccioli C, Chastre J, Lecompte Y, Gandjbakhah I, Gibert C. Prosthetic valveendocarditis:the case for prompt
surgical management. J THORAC CARDIOVASC SURG 1986;92:784-9. 14. Nunez de la Llana R, GilAguado M, IglesiasA, Larrea JL,
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15.
16.
17.
18.
Celemin D. Bioprosthetic valve endocarditis: indicators for surgical intervention. Ann Thorac Surg 1983;35:262-79. Ivert T, Dismukes WE, Cobbs C, Blackstone EH, Kirklin JW, Bergdahl LA. Prosthetic valve endocarditis. Circulation 1984;69:223-32. Ismail MB, Hannachi N, Fekria A, Zouhair K, Rouge JF. Prosthetic valve endocarditis: a survey. Br Heart J 1987; 58:72-7. Horstkotte D, Evagelopoulos N, Bircks W, Loogen F, Schulte HD. Reoperation for malfunction of heart valve prosthesis, especially with endocarditis. Thorac Cardiovasc Surg 1987;35:16-9. Leport C, Yilde JL, Bricaire F, et al. Fifty cases of late prosthetic valve endocarditis: improvement in prognosis over a 15-year period. Br Heart J 1987;58:66-71.
The Journal of Thoracic and Cardiovascular Surgery March 1993
19. Horstkotte D, Bircks W, Loogen F. Infective endocarditis of native and prosthetic valves-the case for prompt surgical intervention? A retrospective analysis of factors affecting survival. Z Kardiol I986;75(suppl 2):168-82. 20. Cowgill LD, Addonizio YP, Hopeman AR, Harken AH. Prosthetic valve endocarditis. Curr Probl Cardiol 1986; 11:450-7. 21. Frantz PT, Murray GF, Wilcox BR. Surgical management of left ventricular-aortic discontinuity complicating bacterial endocarditis. Ann Thorac Surg 1980;29:1-7. 22. Lau JKH, Robles A, Cherian A, Ross DN. Surgical treatment of prosthetic endocarditis: aortic root replacement using a homograft. J THORAC CARDIOVASC SURG 1984; 87:712-6.
Boundvolumes available to subscribers Bound volumes of THE JOURNAL OFTHORACIC AND CARDIOVASCULAR SURGERY are available to subscribers (only) for the 1993 issues from the Publisher, at a cost of $75.00 for domestic, $98.25 for Canadian, and $93.00 for international subscribers for Vol. 105 (JanuaryJune) and Vol. 106 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue of the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Subscription Services, 11830 Westline Industrial Drive, St. Louis, Missouri 63146-3318, USA; phone (800) 325-4177, ext. 4351, or (314) 453-4351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular JOURNAL subscription.
Prosthetic valve endocarditis Experience with porcine bioprostheses Prosthetic valve endocarditis remains an infrequent but serious complication of cardiac valvular replacement. Prosthetic valve endocarditis was diagnosed in 56 (1.8 %) of 3200 patients in whom one or more porcine bioprostheses were implanted between 1975 and 1988. Of the 56 patients with prosthetic valveendocarditis, there were 40 men and 16 women, with a mean age at initial implantation of 57 years (27 to 81 years). Of the 56 patients, 6 were initiaUy treated for native valve endocarditis. There were 8 cases of early prosthetic valve endocarditis (defined as occurring less than 60 days after initial surgical intervention) and 48 cases of late prosthetic valve endocarditis (occurring after 60 days). The overaU mortality rate of the 56 patients was 32 % (18 patients). Of the 8 patients with early prosthetic valve endocarditis, 6 (75 %) died. Of the 48 patients with late prosthetic valve endocarditis, 12 (25 %) died. The predominant organisms were Staphylococcus epidermidis (12 cases), Streptococcus viridans (8 cases) and Staphylococcus aureus (7 cases). The presence of hemodynamic compromise, including congestive heart failure, septic embolism, persistent sepsis, and echocardiographic evidence of vegetations, dictated the mode and timing of the addition of surgical intervention to medical therapy. The survival rate for medically and surgicaUy treated patients with late prosthetic valve endocarditis was 91 % (20 patients); none of the patients with early prosthetic valve endocarditis survived (aU had severe hemodynamic compromise). We analyzed 18 factors for the prediction of early and late death. The predictors of death by univariate analysis for both early and late prosthetic valve endocarditis were age, diagnosis time, renal status, sepsis, management mode, fever, dental procedures, and dental prophylaxis. The predictors by multivariate analysis were age, diagnosis time, renal status, and management mode for early prosthetic valve endocarditis, and only diagnosis time for late prosthetic valve endocarditis. Annular abscess formation occurred in 27 % of the patients. There were no complex aortic or mitral reconstructions. There was one reoperation for recurrent and residual endocarditis. There was one late death as a result of recurrent prosthetic valve endocarditis. We advocate early diagnosis and aggressive combined medical and surgical treatment before the development of hemodynamic compromise and other characteristic signs when the culprit organisms are Staphylococcus aureus, gram-negative organisms, and Candida albicans. (J THORAe CARDIOVASC SURG 1993;105: 428-34)
S. S. Sett, MD,a M. P. J. Hudon, MSc,a W. R. E. Jamieson, MD,a and A. W. Chow, MD,b Vancouver, British Columbia, Canada
From the Department of Surgery, Division of Cardiovascular and Thoracic Surgery; and the Department of Medicine, Division of Infectious Diseases," University of British Columbia, Vancouver General Hospital, Vancouver, Canada.
Address for reprints: W. R. E. Jamieson, MD, Division of Cardiovascular and Thoracic Surgery, Department of Surgery, University of British Columbia, 3100-910 West 10th Ave., Vancouver, B.c. Canada V5Z 4E3.
Read at the Sixteenth Annual Meeting of The Western Thoracic Surgical Association, Coronado, Calif., June 20-23, 1990.
0022-5223/93 $1.00 +.10
428
Copyright
Cc)
1993 by Mosby-Year Book, Inc. 12/6/41884
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 3
Prosthetic valve endocarditis (PVE) remains a feared complication ofvalve replacement, even in the modern era of antimicrobial therapy. The overall occurrence of PVE is in the range of 2% to 4%.1 From 1975 to 1988, we studied clinical courses and outcomes for patients who had PVE. 2-8 Both the Hancock standard (Medtronic Cardiopulmonary Division, Minneapolis, Minn.) and the Carpentier-Edwards standard porcine bioprostheses (Baxter Healthcare Corp., Edwards Div., Irvine, Calif.) were introduced at our center in 1975,2-7 and the Carpentier-Edwards supraannular prosthesis was introduced in 1982.8 The purpose of this retrospective review was to identify those factors that influence survival in a population with PVE restricted to porcine bioprostheses. Patients and methods The patient population was determined by a retrospective review of patients who had endocarditis related to porcine bioprostheses between 1975 and 1988. A total of 3200 patients underwent implantation of porcine bioprostheses during this period.These patients had the Hancock standard, the Carpentier-Edwards standard, or the Carpentier-Edwards supraannular prosthesisimplanted in aortic, mitral, or multiple positions. Patients who had undergone concomitant procedures, such as coronary artery bypass, were included. There were no dramatic changes in operative technique throughout the period of review. The majority of valves were implanted by means of interrupted sutures with strips of Teflon fluorcarbon resins or pledgets; some were implanted by means of continuous monofilament sutures. All patients received prophylactic antibiotic coverage in the perioperative period. Current practices include the use of a cephalosporinor vancomycin hydrochlorideand an aminoglycosidein the perioperative period,extended t048 hours postoperativelyor until all central lines are removed. Follow-up of survivorswas obtained through the valve registry at the University of British Columbia. Definitions. The diagnosis of PYE was based on the following":(I) two blood cultures positivefor the same organism in a patient with a compatible clinical syndrome that consisted of fever, new cardiac murmurs, splenomegaly, petechiae, Roth's spots, Osler's nodes, or Janeway's lesions and (2) histopathologicevidenceof endocarditis in a surgical or autopsy specimen. Endocarditis that was diagnosed within 60 days of operation wasclassified as early postoperativeendocarditis, whereas those cases that occurred after 60 days were classified as late.l? Data analysis. We analyzed 18 variables as predictors of early and late mortality: (I) age, (2) sex, (3) history of drug abuse, (4) type of valve implanted (Carpentier-Edwards standard, Carpentier-Edwards supra-annular, or Hancock standard), (5) valve position (aortic, mitral, tricuspid, or combination thereof), (6) time to diagnosis, defined as the time from onset of symptoms to the first hospital admission because of PYE, (7) renal status with renal insufficiency indicated by a sustained increase in serum creatinine, (8) presence of ongoing sepsis, definedas persistent elevationof white blood count com-
Sett et al.
429
Table I. Distribution of PVE patient population (n = 56) by valve position and deaths
Totals
Valve position
Early PVE
Late PVE
AVR MYR MR 8
4 (3) 3 (2) I (I) 8 (6)
23 (7) 17 (4) 8 (I) 48 (12)
PVE, Prosthetic valve endocarditis; AVR, aortic valve replacement; MVR, mitral valve replacement; MR, multiple valve replacement; ( ), denotes deaths.
bined with compatible clinical picture, (9) type of organism, (10) presenceof conduction abnormality, (I I) New York Heart Association classification, (12) history of embolic event, (13) mode of management (either medical or combined medical and surgical therapy), (14) specificantibiotic used, (15) presence of fever, (16) dental procedure before episode of PYE, (17) no history of dental prophylaxis, (18) history of native valve endocarditis (NYE). Statistical methods. Univariate analysis was performed with Student's t test and the X2 test to assess all relationships of the independent variables to the outcome, the dependent variable. Multivariate analysis was performed with a stepwise or Cox logistic regression analysis with the outcome as the dependent variable. Both groups, early and late PYE death, were evaluated. Results PVE was diagnosed in 56 (1.8%) of 3200 patients who had one or more porcine bioprostheses implanted between 1975 and 1988, In 42 patients PVE was diagnosed on the basis of two or more positive blood cultures and a clinical syndrome that was compatible with endocarditis, whereas 30 patients had histopathologic evidence of PVE at the time of surgical intervention or autopsy. The distribution of the 56 patients by valve position and classification of PVE is shown in Table I. The mean age at initial surgical intervention was 57 years, with a range of 27 to 81 years. Six patients (10.6%) had undergone valve replacement previously for NVE. There were 8 cases of early PVE that occurred at a mean of 26.1 ± 21.9 days after surgical intervention and 48 cases of late PVE that occurred at a mean of 38.4 ± 32.5 months, The predominant number of cases of PVE occurred in the aortic position (27 of 56 patients). Twenty patients had endocarditis involving a mitral prosthesis, and nine had endocarditis involving multiple valve replacements (Table I). The overall mortality rate for the 56 patients with PVE was 32% (18/56). The mortality rate was 75% (6/8) in the early PVE group and 25% (12/48) in the late PVE group. The most common organisms were Staphylococcus
The Journal of Thoracic and Cardiovascular Surgery March 1993
4 3 0 Sett et al.
Table II. Distribution ofpathologic organism by time of onset of PVE and deaths Organism Staphyloccus aureus Staphylococcus epidermidis Streptococcus viridans Hemolytic Streptococcus Enterococcus Diphtheroids Pseudomonas aeruginosa Serratia marcescens Candida albicans Klebsiella pneumonia Actinomycetes actinomycetocomittans Culture negative Multiple Total
0, Denotes
Fig. 1. Mode of treatment (medical and surgical).
epidermidis, then Streptococcus viridans and Staphylococcus aureus (Table II). Eleven patients had cultures that tested negative for endocarditis. Two patients with early PYE caused by Staphylococcus epidermidis were treated medically and survived (Table II). There were seven patients with Staphylococcus aureus PYE. Four of these survived and three died. Three of four survivors underwent combined medical/surgical therapy. The three patients who did not survive had undergone medical treatment alone. Gram-negative organisms predominated in the early PYE group (Table II). All of these patients died. There were four patients with PYE that was caused by Candida albicans; two survived and two died. One patient who had candidal septicemia after double valve replacement of the aortic and mitral valves underwent combined medical treatment and double valve rereplacement and survived. The other survivor with late candidal PYE had both valves replaced as well. One patient with candidal PYE involving a mitral prosthesis died while receiving medical treatment, and the final patient, who had undergone replacement of aortic and mitral valves, died of candidal septicemia with multiorgan failure after combined medical/surgical therapy.
Early PVE I
(I)
2 (-)
Late PVE 6 (2) 10 (4) 8 (2) 1(-)
(I) (I) (I) (I) (I)
2 (-) 1(-) 1(-)
3
(I)
4
(I)
II (2) 1(-) 48 (12)
deaths.
Causes of death in patients who experienced early PYE were septicemia, congestive heart failure, and thrombotic occlusion of a mitral prosthesis (in one patient). The causes of death in patients with late PYE were congestive heart failure, hepatic and renal failure, septicemia, ruptured mycotic aneurysm, and adult respiratory distress syndrome. These occurred singly or in combination. Ofsix patients with previous NYE, early PYE occurred in one and late PYE occurred in five. The patient who had early PYE died of Pseudomonas septicemia; the original NYE organism was Staphylococcus aureus. One patient in the late PYE group had Candida albicans septicemia after double valve replacement for NYE, which was caused by Staphylococcus epidermidis. The case was mentioned in the preceding paragraph. The patient in the late PYE group who died had a history of chronic intravenous drug abuse and had undergone mitral and tricuspid valve replacement. In only one patient in the late PYE group was Streptococcus viridans the original organism in NYE. The others were dissimilar or had negative cultures. Figs. 1 and 2 illustrate the outcomes after both medical treatment alone and combined medical and surgical treatment in early and late PYE, respectively. After medical treatment, two patients survived early PYE. However, 91 % of the patients with late PYE survived after combined medical and surgical therapy whereas 62% of those who had medical therapy alone survived (p < 0.01). Fig. 3 denotes the numbers of patients who were found to have annular abscesses, dehiscence, vegetations, and
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Sett et al.
43 I
Perforation
Vegetations
Dehiscence
AnnularAbscess
w
~
~
~
~
00
M
00
00
100
26 Reoperated Cases
Fig. 3. Findings at reoperation.
Only time to diagnosis was found to be a predictor of late mortality after multivariate analysis. Follow-up was completed in all patients, and there was one subsequent death that was related to recurrent PVE. This patient had an upper gastrointestinal tract hemorrhage and Staphylococcus epidermidis septicemia and died after cardiac arrest. Autopsy confirmed a chronic annular abscess around the aortic prosthesis. Fig. 2. Mode of treatment (medical).
perforations. Only 27% (7/26) of the patients who had undergone a second operation had annular abscesses. Of the seven patients in whom annular abscesses formed, five had undergone previous aortic valve replacement and two had undergone multiple valve replacement. Dehiscence was the dominant finding in 42% (11/26) of patients with reoperation. The other findings were vegetations in 35% (9/26) and leaflet perforations in 31% (8/26). There were no complex aortic root or mitral procedures in this series. Eighteen variables listed in Table III were used for univariate and multivariate analyses in the determination of predictors of death in both early and late PVE. In both the early and late groups, univariate analysis revealed that renal status (renal insufficiency that was indicated by a sustained rise in serum creatinine level), presence of ongoing sepsis, mode of treatment, presence of fever, previousdental procedure, lack of dental prophylaxis, time to diagnosis (defined as the time from the onset of symptoms to the first hospital admission), and age of patient if over 65 were predictors of death (p < 0.05). However, multivariate analysis revealed that renal status (p < 0.05), mode of treatment (p < 0.05), time to diagnosis (p < 0.04), and age (p < 0.05) were predictors of early death. Renal status was the strongest predictive factor.
Discussion Mortality rates that are associated with PVE have been improving since it was realized that the indications for surgical intervention should be liberalized and should not be reserved for only those patients who have severe congestive heart failure, valvular dysfunction, or multiple septic emboli or who have undergone a prolonged course of antibiotic therapy. 11-20 Even with early surgical intervention, mortality rates remain high and range from 23% to 69% in those patients with PVE, both mechanical and heterograft.': 11-13, 15. 18,20 Specifically, early PVE can be considered more precarious, with mortality rates that range from 43% to 100%.1.11-13,17,18 Mortality rates are lower in late PVE and range from 21% to 67%.1, II, 12, 16, 18 Infections in tissue valves tend to occur in the fibrin layer that covers the cusps rather than in the valve ring; infection that occurs in the latter area may subsequently form an annular abscess, although these still may occur in other areas.i" Vegetations may also form on the leaflet surface and lead to destruction or stenosis.!" The occurrence of valve ring abscess in a study that included primarily mechanical valves/" ranged from 50% to 75%; because of this complication, medical therapy alone was not successful. Extensive abscess formation may also necessitate the use of major reconstructive procedures for repair of the aortic rootl': 21, 22 or reconstruction of the mitral valve anulus.l'
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4 3 2 Sett et al.
Table III. Analysis offactors associated with mortality by time ofonset of PVE Analysis: Early PVE (late PVE) Variable Age Sex Drug abuse Valve type Valve position Diagnosis time Renal status Sepsis Organism Conduction abnormality NYHA class Embolism ~anagementmode
Antibiotic Fever Dental procedures Dental prophylaxis Native valve endocarditis Current status
Univariate*
p Value
x (X)
p < 0.05 (p < 0.05)
X
p<0.05
X (X) X (X) X (X)
p < 0.05 (p < 0.05) P < 0.05 (p < 0.05) P < 0.05 (p < 0.05)
X (X) X
p
X (X)
p
X
p<0.05
X (X) X (X) X (X)
p < 0.05 (p < 0.05) P < 0.05 (p < 0.05) P < 0.05 (p < 0.05)
< 0.05 (p < 0.05)
p Value
Multivariatet
< 0.04 (p < Om)
p<0.007
PVE, Prosthetic valve endocarditis; NYHA, New York Heart Association. 'Student's t test and x2 test
tStepwise or Cox logistic regression analysis
No complex reconstructions were performed in this series. None of the patients who underwent a second operation had postoperative valvular dehiscence. The absence of complex reconstructive procedures may be related to the exclusion of mechanical prostheses and the annular abscess formations that almost inevitably accompany them. There was only one instance of a conduction abnormality in this series; surprisingly enough, this was successfully treated with antibiotics and a permanent pacemaker. Conduction system abnormalities are usually associated with annular abscess formation and thus require operative intervention. Emboli were infrequently seen. Conduction abnormalities and emboli were less prevalent than indicated in recent reports.': 16 Renal dysfunction was found to be the strongest predictor of death as a result of early PYE, as seen with multivariate analysis. Baumgartner and colleagues I have also found renal dysfunction to be the most powerful predictor, and this may reflect the occurrence of ongoing congestive heart failure with low-output state and poor renal perfusion. Time to diagnosis was a significant predictor of death in both early and late PYE groups, and this partially reflects the difficulty of establishing definitive suspicion of PYE.
The definitive diagnosis can be made after the specific organism is cultured from blood; the bacteremia is continuous and should show positive results on multiple samplings in more than 99% of the cases, unless there is the presence of a fungal or rickettsial infection or the patient has had previous antibiotic therapy.-" In the present study, 11 cases of culture-negative PYE can be attributed to antibiotic therapy for suspected infection before transfer. The diagnosis of early PYE may be difficult to make; it demands a high index of suspicion and prompt initiation of bactericidal antibiotic therapy. If fever, an elevated white blood cell count, and other signs of sepsis or extracardiac infection subside and there is no persistent bacteremia, then therapy should be continued for 10 to 14 days. However, if systemic signs of toxicity persist and are accompanied by a new or changing murmur, persistent bacteremia, or both, early PYE should be suspected, echocardiography should be performed, and emergency reoperation should be considered. In this present study two survivors of early PYE underwent medical therapy alone, whereas six patients in the same group who were in the process of combined medical/surgical therapy died. Of note, in the two survivors Staphylococcus epidermidis was the culprit orga-
The Journal of Thoracic and Cardiovascular Surgery Volume 105, Number 3
nism, and both patients were treated successfully with antibiotics. Although our experience is small, it is postulated that early PVE in which Staphylococcus epidermidis is the offending organism can be successfully managed with intensive medical therapy. There was a 66% mortality rate in patients with late PVE who underwent medical treatment only, compared with a 9% mortality rate in those patients who underwent combined medical/surgical therapy. Ivert and colleagues'> found that 70% of their patients died after medical treatment, but their group consisted of patients with both mechanical and tissue valves. Horstkotte and colleagues'" found that six of seven patients died after conservative therapy. It appears that prompt surgical intervention should be instituted in late PVE after the initiation of antibiotic therapy, before the development of congestive heart failure or persistent sepsis (fever, persistently elevated white blood count, shift to the left, continuous bacteremia). Results from this study suggest that all cases of PVE that are caused by Staphylococcus aureus should be treated medically and with early surgical intervention. In this series only one patient who was treated with antibiotics survived a Staphylococcus aureus PVE, which occurred in a mitral prosthesis; all others died. Furthermore, all patients with early PVE that was caused by gram-negative organisms died. Although these patients underwent combined medical/surgical therapy, the surgical intervention occurred at a time when there was marked hemodynamic compromise. It must be speculated that if surgical treatment had been instituted earlier, the outcome would have been different. Two patients survived candidal PVE after surgical treatment. Fungal PVE mandates reoperation. The only survivors of early PVE had Staphylococcus epidermidis and were treated medically. Staphylococcus epidermidis may be a unique organism, less virulent, and susceptible to eradication with medical therapy. There were three cases of recurrent endocarditis in this series (8%). One patient was undergoing medical treatment at the time of the study. One patient underwent repeat double valve replacement for Candida albicans endocarditis and was doing well at the time of this study. The additional patient was admitted with an upper gastrointestinal tract hemorrhage and Staphylococcus epidermidis septicemia. He had a cardiac arrest and died in the intensive care unit. Autopsy revealed a chronic annular abscess around the aortic prosthesis. Two series': 15 have recurrent PVE rates of 15% and 9.4%, respectively.
Sett et al.
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The results of the present study indicate that NVE is not an incremental risk factor for the development of PVE. These findings are dissimilar to those of Ivert and colleagues.P REFERENCES I. Baumgartner WA, Miller DC, Reitz BA, et al. Surgical treatment of prosthetic valve endocarditis. Ann Thorac Surg 1983;35:87-104. 2. Jamieson WRE, Munro AI, Miyagishima RT, Allen P. Clinical evaluation of porcine heterograft cardiac valvesin 200 patients. Can J Surg 1978;21:133-5. 3. Janusz MT, Jamieson WRE, Allen P, et al. Experience with the Carpentier-Edwards porcine valve prosthesis in 700 patients. Ann Thorac Surg 1982;34:625-33. 4. Janusz MT, Jamieson WRE, Allen P, et al. Long-term follow-up of patients with porcine cardiac valve prosthesis. Can J Surg 1983;26:160-2. 5. Jamieson WRE, Pelletier LC, Janusz MT, Chaitman BP, Tyers GFO, Miyagishima RT. Evaluation of the Carpentier-Edwards porcine bioprosthesis implanted over the years. J THORAC CARDIOVASC SURG 1984;88:324-33. 6. Jamieson WRE, Tyers GFO, Gerein AN, Miyagishima RT, Munro AI, Burr LH. Carpentier-Edwards standard porcine bioprosthesis: assessment of valve-related complications. Thai J Cardiovasc Thorac Surg 1987;8: 17380.
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19. Horstkotte D, Bircks W, Loogen F. Infective endocarditis of native and prosthetic valves-the case for prompt surgical intervention? A retrospective analysis of factors affecting survival. Z Kardiol I986;75(suppl 2):168-82. 20. Cowgill LD, Addonizio YP, Hopeman AR, Harken AH. Prosthetic valve endocarditis. Curr Probl Cardiol 1986; 11:450-7. 21. Frantz PT, Murray GF, Wilcox BR. Surgical management of left ventricular-aortic discontinuity complicating bacterial endocarditis. Ann Thorac Surg 1980;29:1-7. 22. Lau JKH, Robles A, Cherian A, Ross DN. Surgical treatment of prosthetic endocarditis: aortic root replacement using a homograft. J THORAC CARDIOVASC SURG 1984; 87:712-6.
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