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Ann Thorac Surg 1997;63:1718-1724
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Is There an Advantage to Repairing Infected Mitral Valves?

Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, Ohio

Accepted for publication December 24, 1996.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Background. The therapy for native mitral valve endocarditis is in evolution. Antibiotics have significantly improved survival rates, but patients with complications of endocarditis may require surgical treatment.

Methods. Between January 1985 and December 1995, 146 patients underwent surgical therapy (repair or replacement) for native mitral valve endocarditis. All patients had documented bacterial endocarditis. Univariate and multivariate analyses were performed to determine predictors of hospital death, long-term event-free survival, and probability of repair. Patients were evaluated in three groups: all patients, patients with acute endocarditis, and patients with chronic endocarditis.

Results. There were ten hospital deaths (6.8%). Patients undergoing repair had a lower hospital mortality rate (p = 0.008) then those having replacement. Event-free survival was improved after mitral valve repair in the overall group (p = 0.02) and in the group with healed (chronic) endocarditis (p = 0.05). Although the acute endocarditis group demonstrated an improved event-free survival rate after mitral valve repair versus replacement (74% versus 20% at 6 years), this did not reach statistical significance.

Conclusions. We conclude that mitral valve repair is preferable to mitral valve replacement when possible, in patients with complications of endocarditis, as repair results in a lower hospital mortality and an improved long-term survival.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Native mitral valve endocarditis remains a great challenge to cardiac surgeons. Prior to the antibiotic era, mitral valve endocarditis was a uniformly fatal disease. Antimicrobial therapy resulted in survival rates of 75% [1]. Patients with more virulent forms of infection, however, may not respond to drug treatment and may have development of complications requiring operative intervention because of congestive heart failure, uncontrolled sepsis, or vegetation embolization.

Prosthetic valve replacement has traditionally been the standard therapy for patients unresponsive to antibiotic therapies [2, 3], but valve replacement is associated with several long-term problems [3, 4]. The life expectancy of bioprosthetic valves is limited, especially in the mitral position [4, 5]. Lifelong anticoagulation is required if a mechanical prosthesis is used and is associated with bleeding and thromboembolic complications. Young women who wish to get pregnant cannot take oral anticoagulants because of their teratogenic effects. Moreover, valve replacement in the presence of acute endocarditis carries a high perioperative mortality rate and a substantial risk of prosthetic valve endocarditis [4, 5].

Our initial experience with mitral valve repair in patients with endocarditis has been reported [6]. We report here our experience with 146 patients undergoing mitral valve repair or replacement for endocarditis. It was undertaken to determine any advantages to repairing infected mitral valves and to determine which patients with mitral valve endocarditis could undergo repair.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Between January 1985 and December 1995, 146 patients underwent surgical therapy for complications of native mitral valve endocarditis. Mean age was 51.9 ± 16.4 years (range, 5 to 82 years). There were 100 male patients (68%). All patients had culture-documented bacterial endocarditis of the mitral valve. Acute infection was considered present if the patient had positive blood cultures, operative findings of acute inflammation, or positive cultures or Gram's stain of excised tissue. Endocarditis was considered healed and inactive if operation occurred more than 6 weeks after the initial diagnosis, a course of antibiotics was completed, blood cultures were negative at the time of operation, and cultures and Gram's stains of intraoperatively excised tissue were negative.

Early in our series, an attempt was made to have patients complete at least a 2-week course of antibiotics prior to surgical intervention. However, as our experience and confidence in mitral valve repair techniques increased, patients demonstrating clear indications for surgical intervention (hemodynamic deterioration, persistent sepsis, or mobile vegetations identified by echocardiography) were operated on with less than 1 week of antibiotic treatment. Our current preference is to intervene earlier in patients requiring operation to prevent valve leaflet destruction, which may preclude valve repair, to prevent systemic embolization from large vegetations, and to preserve ventricular function.

Presenting symptoms included shortness of breath in 71 patients, fever in 42, embolic events in 22, and syncopal episodes in 11.

One hundred two patients (70%) underwent mitral valve repair; 44 were treated with mitral valve replacement. Fifty-eight patients had evidence of acute endocarditis (39.7%), and 88 had healed (chronic) endocarditis. The presumed origin of the mitral valve endocarditis was found in only 46% of patients. Dental manipulation (35 patients) and distant superficial wounds (20 patients) were the most frequent predisposing factors. Other origins of infection included drug addiction, 5 patients; gynecologic, 3; arteriovenous fistula (dialysis), 3; and central line, 1 patient; the source was not determined in 79 (54%). The microorganisms responsible for infection were isolated from blood in 99 patients (68%) before operation (Table 1). Streptococcus and Staphylococcus species predominated. There were no cases of fungal endocarditis.

Indications for operation included hemodynamic deterioration (congestive heart failure and hypotension) in 103 patients (70.5%). Thirty-eight patients (26%) had evidence of mobile vegetations on echocardiography, and 5 patients had uncontrolled sepsis.

	Operative Findings

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
The mitral valve findings at the time of operation are shown in Table 3. Chordal rupture, leaflet perforation, and vegetations were the most frequent findings. Fourteen (16%) of the 88 patients with chronic (healed) endocarditis had calcified vegetations. Four patients had previously repaired abnormal mitral valves with evidence of infection and dehiscence of the annuloplasty ring in each. Two underwent re-repair and 2, mitral valve replacement. Associated procedures were required in 74 patients: aortic valve replacement in 33; coronary artery bypass grafting in 22; aortic valve repair in 6; tricuspid valve repair in 10; resection of an atrial myxoma in 2; septal myotomy and myectomy in 1; and atrial septal defect repair in 1.

	Operative Technique

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

All patients operated on for acute endocarditis received 6 weeks of parenteral antibiotic therapy postoperatively. Patients undergoing mechanical valve replacement were placed on a lifelong regimen of warfarin therapy, as were patients in chronic atrial fibrillation. Patients receiving bioprosthetic valves had 6 weeks of anticoagulation therapy.

	Follow-up

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Follow-up was performed between July and August 1995 by questionnaire or direct calls to the patients or their referring physicians. Follow-up was 99% complete at a mean of 3.7 ± 2.2 years. Five hundred two patient-years of follow-up were available for analysis.

	Statistical Analysis

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Univariate analysis of preoperative patient history and physical characteristics, echocardiographic, bacteriologic, and operative findings, and type of repair was performed for the overall group, the acute endocarditis group, and the chronic endocarditis group to assess differences between the repair and replacement groups. Student's t test was used to compare continuous variables and Fisher's exact test, to compare categoric variables. Univariate analysis was used to determine possible predictors of hospital death and event-free survival using a p value of less than 0.1 as a cutoff for significance. Significant factors were then placed into a multivariate logistic regression analysis to determine predictors of hospital death and event-free survival. A p value of less than 0.05 was considered significant.

	Results

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
All Patients
Patients undergoing mitral valve replacement had diabetes (p = 0.005), hypertension (p = 0.02), previous open heart operation (p = 0.02), and mitral stenosis (p = 0.009) more frequently than did patients undergoing mitral valve repair. Patients undergoing mitral valve replacement had more mobile vegetations on preoperative echocardiography (p = 0.04), congestive heart failure (p = 0.005), and white blood cell counts greater than 20,000/µL when seen (p = 0.005) and were operated on for acute endocarditis (p = 0.000001) more frequently than patients undergoing repair. At operation, patients who required mitral valve replacement were found to have more vegetations (p = 0.002) and were more likely to require concomitant aortic valve replacement (p = 0.01) or coronary artery bypass grafting (p = 0.02) than patients having repair.

Patients requiring mitral valve replacement were older (p = 0.05), had lower starting hematocrits (p = 0.0002) and higher serum creatinine levels (p = 0.005), received intravenous antibiotics longer (p = 0.0002), had longer bypass runs (p = 0.004) and longer cross-clamp times (p = 0.02), and required more packed red blood cells (p = 0.0004), more platelets (p = 0.02), and more fresh frozen plasma transfusions (p = 0.01) than patients undergoing valve repair.

There were ten hospital deaths (eight in the acute endocarditis group and two in the chronic endocarditis group), for an overall mortality rate of 6.8%. Four patients each died of prosthetic valve failure and cardiac failure, and 1 patient each died of a cerebrovascular accident and respiratory failure. Patients undergoing repair (acute and chronic endocarditis groups) had a lower overall hospital mortality rate (p = 0.008) (Table 5). Multivariate logistic regression analysis failed to identify any predictors of hospital death.

	Acute Endocarditis Group

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Patients with acute endocarditis were analyzed separately, as they represented a higher-risk subset of patients. Patients requiring mitral valve replacement received more packed red blood cells (p = 0.01), fresh frozen plasma (p = 0.002), and platelet transfusions (p = 0.07) than patients able to have repair. There was no difference in age, preoperative hematocrit, creatinine level, bypass time, cross-clamp time, days on a regimen of antibiotics prior to operation, days in the intensive care unit postoperatively, associated mitral stenosis, left ventricular function, preoperative shock, mobile vegetations on echocardiography, congestive heart failure, number of patients with a white blood cell count greater than 20,000/µL at presentation, or need of concomitant procedures between the valve replacement and valve repair subgroups. However, there was a trend toward a higher mortality rate (p = 0.06) in the mitral valve replacement subgroup.

	Chronic Endocarditis Group

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
The patients with healed (chronic) endocarditis were also evaluated separately. There was no difference in any presenting symptoms, preoperative characteristics, echocardiographic findings, or operative details between the repair and replacement subgroups. More patients undergoing valve replacement had preservation of one or both mitral valve leaflets than in the acute endocarditis group (54% versus 42%). This did not reach significance (p = 0.5). There was no difference in hospital mortality between the repair and replacement subgroups.

	Complications

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Postoperative complications were common. Atrioventricular block developed in 14 patients. Respiratory failure necessitating readmission to the intensive care unit or prolonged ventilation beyond 72 hours occurred in 9 patients and postoperative embolic events in 8. Postoperative intraaortic balloon pump placement was necessary in 7 patients. Arrhythmias necessitating intravenous antiarrhythmic agents developed in 6 patients, and sternal wound infection or gastrointestinal bleeding occurred in 3 patients each. Groin infections developed in 2 patients. There was no difference in the incidence of complications within the repair and replacement subgroups between the acute or chronic endocarditis groups. Likewise, there was no difference between all patients undergoing repair or replacement.

Two patients required reoperation while in the hospital postoperatively. Both eventually had valve replacement. One was a 64-year old woman who underwent mitral valve repair and coronary artery bypass grafting for ischemic mitral insufficiency. The mitral valve repair failed because of endocarditis, thus necessitating re-repair 10 weeks later. Infection occurred again, and valve replacement was performed. The patient was subsequently discharged from the hospital. The second patient underwent aortic and mitral valve replacement for bivalvular endocarditis. Nine weeks later, valve re-replacements were required for prosthetic valve endocarditis. At postmortem examination, the fibrous skeleton of the heart was infected, and there was evidence of persistent prosthetic valve endocarditis in both valves.

	Event-Free Survival

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Event-free survival, including late deaths, thromboembolic events, need of reoperation (as a result of recurrent infection, valve repair failure, or prosthetic valve degeneration), and cerebrovascular accidents at 6 years are demonstrated in Figures 1 through 3. Significantly improved event-free survival was found after mitral valve repair in the overall group (p = 0.02) (see Fig 1) and in the chronic (healed) endocarditis group (p = 0.05) (see Fig 3). Reoperation-free survival (96% versus 68%) and reinfection-free survival (95% versus 73%) for all patients were better in the repair group than in the replacement group. Patients having mitral valve repair rather than replacement for acute endocarditis also demonstrated improved event-free survival (74% versus 20% at 6 years), but this failed to reach significance (p = 0.3) (see Fig 2). Multivariate logistic regression analyses revealed predictors of improved event-free survival to be white blood cell count less than 20,000/µL at presentation and no previous open heart operation.

View larger version (18K): [in this window] [in a new window]   Fig 1. . Event-free survival for all patients undergoing mitral valve repair or replacement.

View larger version (16K): [in this window] [in a new window]   Fig 2. . Event-free survival for patients with active (acute) endocarditis undergoing mitral valve repair or replacement.

View larger version (17K): [in this window] [in a new window]   Fig 3. . Event-free survival for patients with healed (chronic) endocarditis undergoing mitral valve repair or replacement.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

Our study also clearly demonstrated that not all patients with complications of endocarditis are candidates for mitral valve repair and, therefore, any comparison between patients having mitral valve repair and patients having mitral valve replacement can be misleading. This is also probably true of all retrospective studies attempting to compare patients undergoing mitral valve repair with those having mitral valve replacement. Some patients undergoing mitral valve replacement had more severely damaged valves as a result of endocarditis, and inadequate leaflet tissue remained for reconstruction. Moreover, several patients requiring mitral valve replacement also underwent associated concomitant procedures (such as aortic valve replacements or coronary artery bypass grafting). This fact accounts for the prolonged cross-clamp and bypass times in these patients and most likely influenced the surgeon's decision not to attempt valve repair. Our study also revealed that patients with vegetations on the anterior or posterior leaflet and those with previous mitral valve repair procedures were more likely to require valve replacement. The appropriateness of comparing repair and replacement patients notwithstanding, patients who could undergo mitral valve repair had a lower hospital mortality rate and better midterm durability than patients who did not have repair. Therefore, when feasible, mitral valve repair should be performed for patients with acute or chronic endocarditis.

The better hospital mortality and event-free survival rates of the repair group are the result of several advantages besides being less ill that patients undergoing mitral valve repair have over those needing mitral valve replacement. Mitral valve repair has been shown to preserve left ventricular function and to avoid the inherent morbidity associated with prosthetic valves [8, 9]. It is now established that ventricular function is better preserved after mitral valve repair than after valve replacement when the chordae are excised, which is more likely to occur in patients with endocarditis (24/34 patients or 71% in our series) [8, 9].

Hospital mortality after mitral valve repair has been demonstrated to be lower than after replacement as a result of the improved ventricular function associated with preserving the subvalvular apparatus [9–12]. Moreover, anticoagulation is not required after mitral valve repair, and therefore, hemorrhagic complications are less common than after valve replacement [8, 9]. Patients undergoing mechanical valve replacement have a linearized rate of events (structural valvular deterioration, thromboembolism, and hemorrhage) of 5% per year [13]. Bioprosthetic valves have similar event rates [14]. Although thrombosis is unlikely to occur in bioprosthetic valves and patients are less likely to experience bleeding complications because anticoagulation is unnecessary, bioprosthetic valves develop structural deterioration at a much greater rate than mechanical valves. Furthermore, by preserving mitral valve leaflets using repair techniques, reinfection is less frequent than when a valve prosthesis is used [8, 9].

Whether intervening earlier in the course of infection before valve destruction occurred might have allowed more patients to undergo repair is unknown. During the period of our study, we adopted a more aggressive approach to patients with native mitral valve endocarditis in an effort to try to repair more mitral valves. In support of this approach, it is known that endocarditis begins on the valve leaflets where it remains for some time [15, 16]. We concur with the philosophy of Dreyfus and colleagues [17] that earlier intervention may help to ensure valve repairability. They thought earlier surgical intervention could prevent progression of the infection process while the patient completed a course of antibiotics. This also increased the likelihood of preserving the subvalvular apparatus and, thus, left ventricular function. Although only 45% of patients in our acute endocarditis group were able to undergo mitral valve repair, Dreyfus and associates [17], using a more aggressive approach to mitral valve repair, reported repair rates of 80% in patients with acute endocarditis.

Our surgical results are similar to those in previously published reports of patients with endocarditis undergoing repair or replacement. With mitral valve repair, Dreyfus and co-workers [17] also demonstrated an excellent hospital mortality rate in patients who had acute endocarditis. Likewise, the hospital mortality rate for mitral valve replacement in our study (overall, 15.9%) is similar to the 10% to 30% rate reported for mitral valve replacement in the setting of acute endocarditis by others [5, 18, 20]. Our study is noteworthy in that we report direct comparison between patients undergoing mitral valve repair and those having replacement for endocarditis, and intermediate results after valve repair for endocarditis are given.

Adequate treatment of the infection process is the major concern when operating for valvular endocarditis [19, 21]. In our study, patients able to undergo mitral valve repair demonstrated superior infection-free survival than those requiring valve replacement (95% versus 73% at 6 years). Published rates of prosthetic valve endocarditis after operation for valvular endocarditis range from 8% to 20% at long-term follow-up [9, 18, 20]. Preserving the native valve tissue during repair and avoiding prosthetic material in an infected area most certainly account for these results. Moreover, mitral valve repair in the presence of active or healed infection demonstrated similar durability and low need of reoperation compared with replacement.

We conclude that it is preferable to repair the mitral valve in patients with complications of endocarditis, as repair results in lower hospital mortality and improved long-term survival. Early intervention may also prevent leaflet destruction, thus ensuring repairability, prevent vegetation embolization, and preserve left ventricular function. Mitral valve repair is durable and resistant to reinfection in the setting of either acute or healed endocarditis. However, it is important to realize that not all patients are candidates for mitral valve repair because of the variable extent of mitral valve tissue destruction caused by endocarditis.

	Acknowledgments

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
We thank Sharon Grechny for typing the manuscript, Christopher Barr and Caroline Apperson-Hansen for statistical analysis, and Karen Mrazeck for data collection.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 
Address reprint requests to Dr Muehrcke, Smithwick Cardiovascular Group, Dillon Professional Building, 1820 Barrs St, Suite 715, Jacksonville, FL 32204.

	References

Top Footnotes Abstract Introduction Patients and Methods Operative Findings Operative Technique Follow-up Statistical Analysis Results Acute Endocarditis Group Chronic Endocarditis Group Complications Event-Free Survival Comment Acknowledgments References

 

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