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Ann Thorac Surg 2000;69:1448-1454
© 2000 The Society of Thoracic Surgeons
a Department of Cardiac Surgery, The General Hospital, Southampton, United Kingdom
Address reprint requests to Dr Monro, Department of Cardiac Surgery, The General Hospital, Tremona Rd, Southampton SO16 6YD, UK
e-mail: monro1711{at}aol.com
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Abstract |
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 Top Abstract IntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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Patients and Methods. One hundred eighteen consecutive patients with positive blood culture up to 3 weeks before operation (or positive valve culture) and macroscopic evidence of lesions typical for endocarditis, undergoing operation between January 1973 and December 1996 in Southampton, were evaluated. The aortic valve was infected in 53 (48.9%), the mitral in 46 (39%), both aortic and mitral in 12 (10.1%), the tricuspid in 4 (3.9%), and the pulmonary valve in 3 (2.5%). Native valve endocarditis was present in 83 (70.3%) and prosthetic valve endocarditis in 35 (29.7%). Streptococci and staphylococci were the most common pathogens. Mean follow-up was 5.6 years (range, 0 to 25 years).
Results. Operative mortality was 7.6% (9 patients). Endocarditis recurred in 8 (6.7%). A reoperation was required in 12 (10.2%). There was 24 late deaths, 17 of them cardiac. Actuarial freedom from recurrent endocarditis, reoperation, late cardiac death, and long-term survival at 10 years were 85.9%, 87.2%, 85.2%, and 73.1%, respectively. On multiple regression analysis the following were independent adverse predictors: pulmonary edema (p = 0.007) and impaired left ventricular function (p = 0.02) for operative mortality; prosthetic valve endocarditis (p = 0.01) for recurrent infection; myocardial invasion by the infection (p = 0.01) and reoperation (p = 0.04) for late cardiac death; and coagulase-negative staphylococcus (p = 0.02), annular abscess (p = 0.02), and longer intensive care unit stay (p = 0.02) for long-term survival.
Conclusions. Operation for active culture-positive endocarditis carries an acceptable mortality. Freedom from recurrent infection, reoperation, and long-term survival are satisfactory. In our data, patients’ hemodynamic status at operation was the major determinant of operative mortality. Prosthetic valve endocarditis, coagulase-negative staphylococcus, and annular or myocardial infectious invasion were the critical adverse determinants of late outcome.
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Introduction |
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TopAbstractIntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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Definitions
Culture-positive infective active endocarditis was defined as the presence of a positive blood culture up to 3 weeks before operation (or positive culture of the excised vale) accompanied by macroscopic evidence of lesions typical for endocarditis at operation [2]. Operative mortality includes any death occurring within 30 days after the operation or within the same hospital admission. Late cardiac death was defined as a terminal event attributed to cardiac causes taking place after patient discharge from the hospital (more than 30 days after the operation). For reasons of clarity the presentation and statistical analysis of the data were based on the patients’ first episode of endocarditis with episodes of recurrent infections or reoperations being described in the relevant paragraphs.
Follow-up
Follow-up information was available for all hospital survivors within 12 months of the closing date of this study. Mean follow-up was 5.8 years (range, 0 to 25 years) with a total of 682.2 patient-years.
Statistics
Univariate analysis
Fifty-four variables were tested with end points being operative mortality, recurrence of infection, reoperation, late cardiac death, and long-term survival (Appendix 1). Categorical variables were compared with 
2 or Fisher’s exact test. Continuous variables were screened with logistic regression and means compared with Student’s t test. Freedom from recurrent infection, reoperation, late cardiac death, and survival, inclusive of operative mortality, were calculated using the Kaplan-Meier product limit method and compared with log rank test.
Multivariate analysis
The variables which attained a p value less than 0.1 on univariate analysis were entered into multiple stepwise logistic regression and Cox proportional hazards logistic regression models. The level of statistical significance in both univariate and multivariate analysis was set at a p value of less than 0.05. All analyses were performed using the statistical package SPSS PC (version 8.0, SPSS Inc, Chicago, IL).
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Results |
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TopAbstractIntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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The aortic valve was infected in 53 (48.9%), the mitral in 46 (39%), both aortic and mitral in 12 (10.1%), the tricuspid in 4 (3.9%), and the pulmonary valve in 3 (2.5%) patients. Native valve endocarditis (NVE) was present in 83 (70.3%) and prosthetic valve endocarditis (PVE) in 35 (29.7%). The aortic valve was more frequently affected among the patients having NVE, as opposed to the mitral in those with PVE (Table 1).
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One hundred seven patients (91.1%) were in New York Heart Association functional class III or IV. Intractable pulmonary edema was present in 19 (16.1%). Renal impairment (creatinine > 130 mg/dL) was present in 65 (55.1%). Fifty-nine (50.0%) had impaired left ventricular function on echocardiography. Thirty-one (26.2%) were in atrial fibrillation, 9 (7.6%) in first- and second-degree heart block, and 3 (2.5%) in complete heart block requiring pacing, with the remaining 75 (63.5%) patients being in sinus rhythm.
Operations, operative findings, and postoperative antibiotic treatment
Before 1978 we used continuous coronary perfusion for aortic and intermittent cross-clamp for mitral valve replacement; subsequently and up to 1995, myocardial protection was achieved with cold crystalloid cardioplegia (St. Thomas’s solution). Since then cold blood cardioplegia has been used. Operative principles were the debridement of all infected tissues and abscess cavities, meticulous washing of all affected areas with povidone iodine solution (Betadine), and reconstruction of resulting defects with glutaraldehyde-treated autologous or bovine pericardium. A homograft, if available, was the preferred substitute for invasive infection in the aortic position.
A total of 90 mechanical valves, 18 bioprostheses, and 13 aortic homografts were implanted; the valve, after excision of the vegetations, was repaired in 9 patients (mitral in 4, tricuspid in 4, and pulmonary valve in 1). Operative procedures and types of valves used are shown in Table 3.
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Although there was not a uniform protocol regarding the postoperative administration of antibiotic treatment during the 24 years of the study period, patients with positive Gram stain or culture of the excised valve, annular abscess, or more extensive infection were likely to receive at least a 6-week course of intravenous antibiotics after their operation. Mean duration of the antibiotic treatment postoperatively was 34.8 days (SD, 14.4; range, 0 to 121 days). Sixty-three (53.3%) received antibiotics for at least 4 and 22 (18.6%) for more than 6 weeks after their operations.
Operative mortality and morbidity
There were nine operative deaths (7.6%) in 6 patients with PVE (16.6%) (five mitral PVE and one aortic PVE) and 3 with NVE (3.6%). Causes of death were sepsis and multiple organ failure in 5, low cardiac output syndrome in 3, and inability to wean from cardiopulmonary bypass in 1 patient. Intractable preoperative pulmonary edema (p = 0.002), older age (p = 0.03), PVE (p = 0.01), mitral PVE (p = 0.01), and impaired left ventricular function (p = 0.04) were significant univariate factors; on multiple logistic regression intractable preoperative pulmonary edema (p = 0.01) and impaired left ventricular function (p = 0.02) were independent predictors of operative mortality.
Sixty-two patients (52.5%) experienced complications after their operation. In 55 (45.7%), these were major, including low cardiac output syndrome in 9, pneumonia in 9, generalized sepsis in 7, acute renal failure in 13, cerebrovascular events in 6, complete heart block necessitating insertion of a permanent pacemaker in 11, bleeding requiring reopening in 6, gastrointestinal bleeding in 2, deep venous thrombosis in 2, and early PVE in 2 patients. Paravalvular leak occurred in 2 patients and was successfully treated with a reoperation within the same hospital admission.
The mean stay in the intensive care unit was 4.1 days (SD, 7.1; range, 1 to 64 days). The mean hospital stay was 32.1 days (SD, 20.6; range, 0 to 115 days).
Late events
One or more late valve-related or thromboembolic events occurred in 18 patients (15.2%): recurrence of infection in 6, severe paravalvular leak necessitating surgical reintervention in 7, mild leak in 4, peripheral thromboembolic episodes in 4, cerebral in 3, and anticoagulation-related bleeding in 5 patients.
Recurrence and reoperation
Endocarditis recurred in 8 patients (6.4%), 2 within 60 days and in 6 more than 60 days postoperatively. Recurrence was higher in PVE (6 patients, 17.1%; 5 mitral and 1 aortic PVE) than in NVE (2 patients, 2.4%; 1 aortic and 1 mitral NVE). Reinfection was recorded only among patients receiving a mechanical prosthesis (n = 81, 9.8% for the mechanical valve group). In comparison, however, against the groups of patients receiving bioprostheses (n = 16) or homografts (n = 12) or having a repair (n = 9), the differences were not significant (p = 0.2). Both patients with early PVE underwent a reoperation with one operative death. Three patients with late PVE underwent operation with one death; 1 patient with coagulase-negative staphylococcal infection and multiple annular, septal, and myocardial abscesses at the initial operation was in very poor condition, was treated conservatively by the physicians, and died. The remaining 2 patients died because of acute or chronic cardiac failure precipitated by gross valvular dysfunction, and a diagnosis of recurrent endocarditis in each case was made only at postmortem examination. Freedom from recurrent infection at 5, 10, and 20 years was 94.6%, 85.9%, and 85.9%, respectively (Fig 1). Prosthetic valve endocarditis (p = 0.008) and mitral PVE (p = 0.003) were significant univariate variables; PVE remained a significant factor for recurrent endocarditis on multiple logistic regression (p = 0.01).
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Late cardiac death
There were 24 late deaths, 17 of them were related to cardiac causes. These included cardiac failure because of severe valve dysfunction in 5, late recurrence in 5, cardiac failure in combination with stroke in 3 and renal failure in 1, structural valve failure in 2, and aortic rupture in 1 patient. Freedom from late cardiac death at 10, 15, and 20 years was 85.2%, 81.7%, and 41.5%, respectively (Fig 2). Significant univariate factors were myocardial involvement by the infection (p = 0.003), annular abscess (p = 0.01), and lack of sinus rhythm (p = 0.03). On Cox multiple regression, extension of the infection into the myocardial tissues (p = 0.002) (Fig 3) and reoperation (p = 0.04) (Fig 4) were significant adverse predictors of freedom from late cardiac death.
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Comment |
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TopAbstractIntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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The assessment of operative risk and late outcome, the identification of factors by which they are influenced, and the comparison of differing treatment strategies applied in these patients are all important. The wide variability in defining what constitutes active endocarditis is, however, one of the reasons that may prevent accurate interpretation and meaningful comparison of published institutional experiences. In this study we have adopted the definition of active endocarditis proposed by the Mayo Clinic in their report in 1995 [2] and have, thus, included only those patients having positive blood culture up to 3 weeks before operation (or positive culture of the affected valve) along with macroscopic evidence of lesions typical for endocarditis at operation.
Microbiology
The microbiologic findings were in accordance with previous reports showing a preponderance of streptococcal and staphylococcal species (Table 2), but their impact on the outcome was different. Staphylococcus aureus, a notoriously virulent and invasive microorganism, has been in previous studies shown to increase the operative risk [1, 8]. Infection by S aureus in this series did not affect any aspect of early or late outcome; in fact, coagulase-negative staphylococcus emerged as the pathogen to be adversely associated with the probability of a long-term survival (Fig 6). This finding stresses the point that coagulase-negative staphylococci can be at least as detrimental as their coagulase-positive counterparts.
Operative morbidity and mortality
The operative morbidity was high, although not dissimilar to the experience reported from elsewhere, and reflects clearly on the patients’ preoperative condition. A high morbidity would, nevertheless, seem to be an acceptable price to pay if one is to attempt to eliminate a persistent infective focus or reverse a downhill clinical course.
The operative mortality was low at 7.6%. This is somewhat higher than the 4% reported by Middlemost and associates [6], nearly identical to 7.4% recently reported by d’Udekem and coworkers [4], and compares favorably with mortality figures of 11.4% to 30% reported by other centers [2, 5, 9–11]. The 3.6% mortality rate for NVE is similar to the 3.8% reported by Dodge and colleagues [12] and the 4% reported by d’Udekem and associates [4] and compares well with operative mortality rates of 6% to 22% reported from elsewhere [1, 2, 7, 8] for patients with active NVE. The 16.6% operative mortality for PVE, in keeping with the bulk of the published evidence, was significantly higher than that for NVE (p = 0.02). Although the Toronto Hospital and Cleveland Clinic have reported an early mortality of 13% [4, 13], in the Mayo Clinic and Harvard Medical School series this was 33% and 22%, respectively [2, 5]. It has been demonstrated that S aureus and annular abscess may significantly increase the risk of early mortality [1, 2, 8]. In our data, however, neither the type of microorganism nor the extent of the infectious invasion were significant variables. Besides PVE, mitral PVE, and older age, all significant univariate factors, the patients’ poor hemodynamic status, expressed as the presence of intractable pulmonary edema or impaired left ventricular function, was the major adverse determinant of operative mortality.
Recurrence and reoperation
The overall 6.5% incidence of recurrence in this series conforms with a relatively low 6% to 7% reported from elsewhere [1, 4, 5, 8]. The 85.9% freedom from recurrent infection at 20 years (Fig 1) seems to be satisfactory, considering the length of the follow-up and the fact that all patients were operated on during the active culture-positive phase of endocarditis. Whereas annular abscess [1, 5], positive culture of the excised valve [1], nonstreptococcal infection [5], and invasive infection beyond the valve leaflets [10] have been significantly associated with recurrent infection in previous reports, PVE was the only variable independently associated with an increased risk of recurrence in our study.
Whether use of mechanical or bioprosthetic valves in active endocarditis provides any advantage is unclear, and the published evidence is conflicting. Cortina and associates [14] reported a higher incidence of recurrence in patients receiving mechanical valves, Sweeny and coworkers [9] and Arvay and Lengyel [15] found bioprosthetic valves were more likely to be reinfected, and others found no aspect of early or late outcome was influenced by the type of the prosthesis implanted [2, 4, 5, 16].
Use of homografts for aortic valve or root replacement has been shown to provide good results in terms of operative mortality and freedom from recurrent infection [17, 18], and Haydock and colleagues [10] found they were associated with a lower incidence of early recurrence in comparison with mechanical valves and bioprostheses. The feasibility of reparative operations for infected mitral or tricuspid valves in the active or healed phase with low mortality and recurrence rates has been well reported [19–21]. Although we did not observe recurrences among patients undergoing either valve replacement with bioprostheses and homografts or valve repair, the numbers were small (Table 3) and the differences not significant. We nevertheless favor the use of homografts in the aortic position for aortic valve or root replacement, although, because of their limited availability, they are mostly reserved for patients with the most invasive forms of endocarditis, and we consider, whenever feasible, to repair the mitral or tricuspid valves as the advantages appear to be obvious.
It may well be that the type of prosthesis used is not as important because early and late good results can be achieved by adequate debridement of the infected tissues, reconstruction of the resulting defects, use of standard mechanical or tissue valves, and administration of appropriate postoperative antibiotics [4, 11]. Current expectations for improved reinfection and reoperation rates with use of silver-impregnated mechanical valves warrant confirmation by relevant mid- and long-term data.
Inevitably reinfection or other mainly valve-related events will lead to a need for reintervention in some patients. The 10.2% reoperation rate in this series and the 87.2% freedom from reoperation at 10 years (Fig 1) are within the reported ranges of 8.2% to 19.8% and 64.0% to 92.0%, respectively [1, 2, 4, 5, 8, 13]. It has, nonetheless, had a serious impact on the outcome being a determinant of late cardiac death (Fig 4).
Late cardiac death and long-term survival
The survival after surgical treatment for active endocarditis is known to be good, with reported 10-year rates ranging from 52.0% to 71.3% [1, 2, 4, 8, 10]. The survival differences in these reports are likely to reflect differences in the clinical and pathologic makeup of the patients involved, and comparisons should, therefore, be undertaken cautiously. The 73.1% actuarial 10-year survival for all patients in our series (Fig 2) (61.1% for PVE, 79.2% for NVE, Fig 5) is rewarding considering the early mortality rate in patients with complicated active endocarditis undergoing solely medical treatment is as high as 50% to 90% [22]. The benefits derived by timely surgical treatment become even more apparent when one observes that for the hospital survivors 10- and 15-year freedom from late cardiac death of 85.2% and 81.2%, respectively (Fig 2), can be expected.
Predictors of long-term survival in previous studies included cardiac failure, renal impairment, PVE [2], New York Heart Association class IV, renal failure [4], cardiogenic shock, mitral valve endocarditis [8], and advanced age [8, 13]. We found that coagulase-negative staphylococcus (Fig 6), annual abscess (Fig 7), myocardial involvement by the infection (Fig 3), and reoperation (Fig 4) were independent negative predictors of the overall long-term survival and freedom from late cardiac death. It is of note, however, that neither the type of pathogen involved nor extension of the infection beyond the valve leaflet (annulus or myocardium) affected the operative mortality. This would show that although surgical techniques and appropriate perioperative multidisciplinary management can avert an unfavorable early outcome, there remains a continuous risk for the sickest of these patients.
Conclusion
This study demonstrates that surgical treatment of patients having culture-positive active infective valve endocarditis, complicated frequently by severe comorbid conditions, can be accomplished with acceptable operative mortality despite high early morbidity. Long-term freedom from recurrent infection, reoperation, and survival would appear to be satisfactory. In our analysis, patients’ hemodynamic status, expressed as intractable preoperative pulmonary edema and poor left ventricular function, was the major determinant of an adverse in-hospital outcome. Prosthetic valve endocarditis, annular or myocardial infectious invasion, and coagulase-negative staphylococcus were identified as the critical determinants of the late outcome.
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Appendix 1. Variables tested on univariate analysis |
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TopAbstractIntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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TopAbstractIntroductionPatients and methodsResultsCommentAppendix 1. Variables tested...References |
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