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Ann Thorac Surg 2007;83:564-570
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Mitral Valve Repair and Replacement in Endocarditis: A Systematic Review of Literature

Harm H.H. Feringa, MDa,*, Leslee J. Shaw, PhDb, Don Poldermans, MD, PhDc, Sanne Hoeks, MSc, Ernst E. van der Wall, MD, PhDd, Robert A.E. Dion, MD, PhDa, Jeroen J. Bax, MD, PhDd

a Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, the Netherlands
d Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
b American Cardiovascular Research Institute, Atlanta, Georgia
c Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands

Accepted for publication September 1, 2006.

* Address correspondence to Dr Feringa, Department of Cardiothoracic Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. (Email: h.feringa{at}erasmusmc.nl).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
BACKGROUND: Several observational studies have suggested a superior survival after mitral valve repair compared with replacement in patients undergoing surgery for infective endocarditis. The objective of this study was to systematically review the rate of morbidity and mortality associated with mitral valve repair or replacement in infective endocarditis.

METHODS: A Medline search was conducted for literature and a systematic review of 24 studies, reporting prognosis of patients who underwent surgery for mitral valve endocarditis, was performed. Information on the patients, type of surgery, and follow-up was abstracted using standardized protocols.

RESULTS: A total of 470 patients (39%) underwent mitral valve repair and 724 patients (61%) underwent valve replacement. Lower in-hospital mortality (2.3% versus 14.4%, relative risk: 0.16, 95% confidence interval: 0.09 to 0.30, p < 0.0001) and long-term mortality (7.8% versus 40.5%, relative risk: 0.19, 95% confidence interval: 0.13 to 0.29, p < 0.0001) were observed among patients undergoing mitral valve repair compared with replacement. In addition, the rates of early reoperation (2.2% versus 12.7%, p < 0.0001), early cerebrovascular events (4.7% versus 11.5%, p = 0.045), late reoperation (4.7% versus 8.7%, p = 0.039), late recurrent endocarditis (1.8% versus 7.3%, p = 0.0013), and late cerebrovascular events (1.6% versus 24.4%, p < 0.0001) were significantly lower after mitral valve repair. Meta-regression analysis demonstrated that mitral valve repair over replacement was associated with a better early and late prognosis after surgery. Male sex and acute surgery were (nonsignificantly) predictive of worse early outcome.

CONCLUSIONS: A systematic review of literature showed that mitral valve repair is associated with good clinical in-hospital and long-term results among patients undergoing surgery for infective endocarditis.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
The estimated incidence of infective endocarditis in the general population has ranged from 16 to 62 cases per million person-years [1–3]. Despite advances in diagnostic techniques and therapeutic strategies, infective endocarditis remains associated with substantial morbidity and mortality, with overall mortality rates for native and prosthetic valve endocarditis as high as 20% to 25% [4].

Treatment for infective endocarditis consists of antibiotic therapy or surgery, or both. Indications for surgical intervention in patients with infective endocarditis include congestive heart failure, new valvular regurgitation, persistent fever or bacteremia despite maximal antibiotic therapy, systemic embolization, and large vegetations on echocardiography with risk of embolization [5–9]. For patients with mitral valve endocarditis, valvular replacement was proposed in the mid 1960s, whereas more recently mitral valve repair has been popularized [10, 11]. For the treatment of degenerative mitral valve regurgitation, mitral valve repair is preferred over mitral valve replacement [12–14]. In the setting of infective endocarditis, however, mitral valve repair may not be feasible because of valvular destruction. In addition, concerns have been raised about the durability of complex mitral valve repair, particularly when performed on infected tissue during acute endocarditis.

Although several studies have suggested a better survival after mitral valve repair compared with mitral valve replacement in patients undergoing surgery for infective endocarditis, these observations are based on data derived from studies with a small sample size. In addition, the presumed benefits of mitral valve repair remain unproven, owing to the lack of randomized controlled trials. A comprehensive overview of morbidity and mortality rates in patients undergoing surgery for mitral valve endocarditis may be helpful and important to physicians and surgeons in their decision making. The current study attempts to systematically summarize outcomes of all available studies on mitral valve repair or replacement for infective endocarditis.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Data Collection
A Medline search was conducted for literature (from January 1980 to May 2005) reporting prognosis of patients who underwent surgery for mitral valve endocarditis. The following key words were used: "infective endocarditis," "mitral valve surgery," "mitral valve reconstruction," "mitral valve repair," and "mitral valve replacement," with all possible combinations allowed. A manual search was also performed in 10 cardiology and cardiothoracic surgery journals (American Heart Journal, American Journal of Cardiology, Annals of Thoracic Surgery, British Heart Journal/Heart, Circulation, European Heart Journal, European Journal of Cardio-Thoracic Surgery, Journal of Heart Valve Disease, Journal of the American College of Cardiology, and Journal of Thoracic and Cardiovascular Surgery). The reference lists of the published original articles obtained through these searches were manually screened for articles that may have been missed. The investigators independently reviewed the list with all the potentially relevant manuscripts. Reviews and abstracts were excluded, and only articles in English language were considered.

Inclusion and Exclusion Criteria
Studies that met the following criteria were included: (1) studies evaluating mitral valve replacement or mitral valve repair in patients who presented with acute or healed infective endocarditis; and (2) the number of patients who underwent mitral valve surgery was available. Studies were excluded when (1) they were anecdotal reports of 4 or fewer cases; (2) in-hospital or long-term follow-up data after mitral valve repair or replacement were not provided; and (3) the publication date was before January 1995. The reason for this last exclusion criterium is that more recently interest in valve repair has increased, and surgical techniques have developed extensively; to reflect current practice, the analysis was restricted to the last decade.

If more than one study was published from a center concerning the same study population, only the study with the largest number of patients was included in the analysis.

Abstraction of Data
The following information was derived from each article: year of publication, characteristics of the study population (age, sex, previous mitral valve surgery), characteristics of infective endocarditis (native or prosthetic valve endocarditis, causative micro-organism, echocardiographic data), surgical data (mitral valve repair or replacement, indication for surgery, acuity of surgery, concomitant aortic or tricuspid valve surgery, perioperative findings), and follow-up data. Acute surgery was defined as surgery before completion of the antibiotic course or surgery within 6 weeks after the diagnosis of endocarditis. The duration of follow-up was noted. Early and late follow-up data included the primary endpoint of death and the secondary endpoint of morbidity. Morbidity results were divided into the following categories: repeat surgery for mitral valve failure, recurrent left-sided endocarditis, cerebrovascular events, and thromboembolic events. Events during early follow-up were defined as occurring during the postoperative in-hospital stay or after hospital discharge but within 30 days after surgery.

Statistical Analysis
All univariate analyses were calculated using Comprehensive Meta-Analysis (available at: www.Meta-Analysis.com; accessed on September 21, 2005). Using the pooled frequency of baseline categorical variables, rates for mitral valve repair versus replacement studies were compared using {chi}2 statistics. For this comparison, when frequency from any of the 2 x 2 tables was zero, a 0.5 was added for the calculation of probability values. For comparisons of continuous variables, mean differences were compared by including the total number of cases, the average value for that patient subset and including the standard difference between groups. From this summary data, a probability value was calculated for differences in mean age, time interval for acute evaluation, and months of follow-up for mitral valve repair and replacement studies (Tables 1 and 2). Go


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  		Table 1. Clinical Characteristics of the Published Studies
 

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  		Table 2. Outcome After Mitral Valve Repair Versus Mitral Valve Replacement
 
The frequency of early and late mortality was collected from each of the published reports. Pooled and summary univariate comparisons of 2 x 2 outcomes were compared with calculate a relative risk ratio. For early and late mortality, a summary relative risk ratio for mitral valve repair and replacement was calculated using a random effects model so as to incorporate a wider berth of uncertainty around the mortality estimate. As follow-up differed between the two procedures, we entered data approximating 3-year mortality rates for all studies. A random effects model is generally employed for observational data, as is evaluated herein. For each of the morbid complications, pooled frequency data for each report was entered into the comprehensive meta-analysis program for calculation of statistical differences between mitral valve repair and replacement.

To adjust for the influence of patient demographics and prognostic indicators that covaried with the dependent variable, a meta-regression was devised using linear regression techniques. The covariates used in the model included sex, mean age of patients, duration of follow-up, type of mitral valve surgical procedure, different indications for surgery, and perioperative findings. From this meta-regression model, the ß coefficient and standard errors were calculated. Only variables with a p value of 0.20 or less were retained for the final meta-regression model of early and late mortality. For all analysis, p values were two-sided, with p values of less than 0.05 considered to indicate statistical significance. Importantly, owing to variability in the year of publication and the potential for concomitant improvements in medicine, we included the year of publication in an early and late mortality model along with the variables listed in Table 3. For early and late mortality, the year of publication did not alter the results presented (p = 0.98 and p = 0.35, respectively).


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  		Table 3. Metaregression Model to Predict Early and Late Mortality
 

   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Characteristics of the Published Studies
By using the different search strategies, 124 full-text articles were retrieved for detailed information. A total of 81 reports were excluded for the following reasons: absence of follow-up data for mitral valve repair or replacement (66 reports), case reports (5 reports), and studies in which results from the same study population were already published in another article (10 reports). For a contemporary comparison between studies, an additional 19 reports were excluded because of publication before January 1995. Accordingly, 24 studies were included for the final analysis (Table 1) [15–39]. These studies included 2,299 patients (mean age, 49 ± 6 years; 74% men) with infective endocarditis, of whom 1,194 (52%) underwent mitral valve surgery. A total of 470 patients (39%) underwent mitral valve repair whereas 724 patients (61%) underwent mitral valve replacement. The mean duration of follow-up was 47 ± 34 months for patients undergoing mitral valve repair and 54 ± 46 months for patients undergoing mitral valve replacement. Of the 24 studies, 7 studies reported follow-up results on patients undergoing mitral valve repair [15–21], 17 on patients undergoing mitral valve replacement [22–33], and 6 on both mitral valve repair and mitral valve replacement [34–39]. The clinical characteristics of the reports on mitral valve repair and mitral valve replacement are presented in Table 1. Acute surgery was more commonly observed in reports that included patients undergoing mitral valve replacement, compared with reports including patients undergoing mitral valve repair. Heart failure, uncontrolled sepsis, and abscess were more common indications for mitral valve replacement, compared with mitral valve repair. The isolation of streptococci was comparable between both groups, whereas staphylococci were more often isolated in mitral valve replacement.

Follow-Up Results
A total of 276 patients (23%) died after mitral valve surgery (Table 2). Early mortality occurred in 115 patients (10%) and late mortality in 161 (13%). Of the 470 patients who underwent mitral valve repair, 33 patients (7.0%) died, as compared with 241 patients (33.3%) who underwent mitral valve replacement (absolute mortality difference; 26.3%, p < 0.0001). Using a random effects model, the pooled estimates of early and late death after mitral valve repair were 2.3% (range, 0% to 9%) and 7.8% (range, 0% to 14%), respectively. The pooled estimates of the incidence of early and late death after mitral valve replacement were 14.4% (range, 0% to 63%) and 40.5% (range, 0% to 84%), respectively. Mitral valve repair was associated with a lower incidence of in-hospital mortality (relative risk: 0.16, 95% confidence interval: 0.09 to 0.30, p < 0.0001) and long-term mortality (relative risk: 0.19, 95% confidence interval: 0.13 to 0.29, p < 0.0001) as compared with patients undergoing mitral valve replacement (Fig 1). In addition, the relative risk for the combined endpoint of in-hospital and long-term mortality was 0.20 (95% confidence interval: 0.14 to 0.28, p < 0.0001) in favor of mitral valve repair (Fig 1).


Figure 1
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  		Fig 1. Summary relative risk (RR) ratio of mitral valve repair versus mitral valve replacement to predict mortality. (CI = confidence interval.)

 
Morbidity results after mitral valve repair and mitral valve replacement are summarized in Table 2. The rates of early reoperation (2.2% versus 12.7%, p < 0.0001), early cerebrovascular events (4.7% versus 11.5%, p = 0.045), late reoperation (4.7% versus 8.7%, p = 0.039), late recurrent endocarditis (1.8% versus 7.3%, p = 0.0013), and late cerebrovascular accident (1.6% versus 24.4%, p < 0.0001) were significantly lower after mitral valve repair, compared with mitral valve replacement.

Meta-Regression Analysis for Early and Late Mortality
All 24 studies were available for meta-regression analysis (Table 3). Results from the meta-regression revealed that early mortality was (nonsignificantly) positively associated with studies including a higher proportion of male patients (p = 0.088). By comparison, mitral valve repair was associated with a lower mortality (p < 0.0001). Moreover, for patients who were operated on during the acute phase of the disease, early mortality was also (nonsignificantly) elevated (p = 0.18). Of the variables assessed for the estimation of late mortality, the use of mitral valve repair was associated with a significantly lower rate of death (p < 0.0001). Additionally, patients of older age had a (nonsignificantly) lower long-term mortality rate (p = 0.068). Other study level variables, such as the indication for surgery, the causative microorganism, and perioperative findings, were not significantly associated with an adverse in-hospital or late outcome (p > 0.20).


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
The results from this systematic review of 24 studies with 1,194 patients undergoing mitral valve surgery for infective endocarditis indicated that in-hospital and long-term mortality were significantly lower after mitral valve repair, compared with valve replacement. In addition, patients who underwent mitral valve repair needed significantly less repeat mitral valve surgery during the early postoperative period and during long-term follow-up; also, patients with valve repair experienced significantly less recurrent endocarditis and cerebrovascular events during long-term follow-up as compared with patients who underwent mitral valve replacement. Meta-regression analysis confirmed that mitral valve repair over replacement was associated with a better outcome both early and late after surgery. Neither the indication for surgical intervention nor the type of causative microorganism was associated with early or long-term outcome.

Mitral Valve Repair and Replacement as Surgical Options
Mitral valve replacement has been the standard surgical therapy for patients with mitral valve endocarditis. More recently, attempts have been undertaken to repair the mitral valve in infective endocarditis, aiming at an improved postoperative and long-term outcome. Mitral valve repair may avoid the insertion of prosthetic material in infected tissue. In addition, early mitral valve repair may prevent worsening of heart failure and progression of valve destruction by the infectious process. During the early stages of the disease, however, the patient’s condition is frequently critical, and reconstructive surgery in inflammatory tissue may be difficult. In published studies, the feasibility of repairing infected mitral valves for acute endocarditis has been demonstrated to vary from 33% to 78% [15, 34–37]. The use of different selection criteria for surgical intervention, different study populations, and different levels of experience in mitral valve repair may explain these wide ranges in feasibility. The durability of mitral valve repair in infective endocarditis has also been questioned. The current results demonstrated low rates of early and late repeat mitral valve surgery (2.2% and 4.7%, respectively) after mitral valve repair, suggesting a favorable long-term durability. In particular, early and late repeat mitral valve surgery was more frequently observed after valve replacement (12.7% and 8.7%, respectively). This observation is likely related to prosthetic-valve–related complications such as paravalvular leaks, valve vegetations, or valve dysfunction, which remain important causes for repeat surgery after mitral valve replacement.

Devastating complications after mitral valve surgery for infective endocarditis include cerebrovascular accidents and recurrent endocarditis. Intracranial hemorrhage frequently occurs owing to anticoagulant therapy. Intracranial embolism may occur because of the thrombogenic nature of mechanical valve prostheses, despite the use of anticoagulation therapy [40]. Recurrent infective endocarditis is frequently associated with the presence of a prosthetic mechanical or biological valve. Use of anticoagulation therapy and prosthetic valves seem plausible explanations for the higher rate of late cerebrovascular events and late recurrent endocarditis after mitral valve replacement compared with mitral valve repair as observed in the current systematic review.

Advantages and Limitations of a Pooled Analysis
A pooled analysis, when well designed and appropriately performed, is a powerful tool to combine in a single conclusion the results of different studies conducted on the same topic. Random effect models were used to control for within-study and between-study variability (random effects modeling). In addition, meta-regression analysis was used to adjust for the influence of patient demographics and prognostic indicators that covaried with the dependent variable. Despite the advantages of a pooled analysis, such as increased statistical power of a comparison and improved estimation of the effect of a treatment, several limitations of the current analysis should be addressed. Publication bias may have influenced our results, as observational studies with a poor outcome may not have been published in full-length papers. Second and most important, surgical techniques and approaches have improved over time, and that may have influenced the current results. To avoid too much influence of developments over time, the analysis was limited to the last decade. Third, the data were collected from observational studies, and these studies did not control for confounding factors in treatment selection; that may have also influenced the results of this pooled data analysis. Finally, the validity of comparing mitral valve repair with mitral valve replacement may be questioned. Mitral valve replacement is often reserved for the sickest patients in whom mitral valve repair cannot be performed. Therefore, it would not be surprising that postoperative results would be worse for these patients. It was indeed observed that mitral valve replacement was more frequently performed in the acute setting, in patients with heart failure, uncontrolled sepsis, and abscesses, or with endocarditis due to Staphylococcus infection.

Implications of the Current Findings
Decision-making about the preferred surgical procedure for mitral valve endocarditis remains controversial. Prospective, randomized controlled trials of mitral valve repair versus replacement have not been conducted yet and may be unethical to perform. Current recommendations about the preferred surgical treatment are based on uncontrolled observational studies including small numbers of patients. In this systematic review, the outcome after mitral valve repair and replacement was evaluated in a large cohort of patients with infective endocarditis. In meta-regression analysis, mitral valve repair remained positively associated with a lower rate of early and late mortality, even after adjustment for possible confounding variables such as indication of surgery, causative micro-organism, and perioperative findings. Other important correlates of early mortality included male sex and acute surgery. Indication for surgery, causative micro-organism, and perioperative findings did not remain significantly associated with adverse outcome, indicating the importance of the surgical procedure itself as determining factor of outcome. We acknowledge that large differences between literature reports in terms of era, patient characteristics, disease severity, and the experience of the surgical team with repair techniques may have influenced the results and limited our study. Accordingly, a recommendation of valve repair rather than valve replacement is inappropriate, and the choice of therapy will depend on the individual circumstances. However, the current pooled analysis clearly demonstrates the feasibility and good outcome of mitral valve repair for endocarditis.

In conclusion, this systematic review of literature showed that mitral valve repair is associated with good early and long-term results among patients undergoing surgery for infective endocarditis. In-hospital and long-term mortality rates were higher after mitral valve replacement. Mitral valve repair should be considered in patients with endocarditis referred for surgery.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

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W. G. Daniel and F. A. Flachskampf
CHAPTER 22 Infective Endocarditis
ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter.
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 Eur. J. Cardiothorac. Surg.Home page
R. Lorusso, S. Gelsomino, G. De Cicco, C. Beghi, C. Russo, M. De Bonis, A. Colli, and A. Sala
Mitral valve surgery in emergency for severe acute regurgitation: analysis of postoperative results from a multicentre study
Eur. J. Cardiothorac. Surg., April 1, 2008; 33(4): 573 - 582.
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 J Am Coll CardiolHome page
S. H. Rahimtoola
The Year in Valvular Heart Disease.
J. Am. Coll. Cardiol., February 19, 2008; 51(7): 760 - 770.
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 Ann. Thorac. Surg.Home page
K. J. Zehr
Invited commentary
Ann. Thorac. Surg., February 1, 2007; 83(2): 570 - 571.
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