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J Thorac Cardiovasc Surg 2009;137:326-333
© 2009 The American Association for Thoracic Surgery

Acquired Cardiovascular Disease

Predictors of recurrence and reoperation for prosthetic valve endocarditis after valve replacement surgery for native valve endocarditis

University of British Columbia, Vancouver, Canada

Received for publication September 25, 2007; revisions received June 18, 2008; accepted for publication August 7, 2008.

^_* Address for reprints: W. R. Eric Jamieson, MD, 486 Burrard Bldg, St Paul's Hospital, 1081 Burrard St, Vancouver, Canada V6Z 1Y6. (Email: eric.jamieson{at}ubc.ca).

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
Objective: Surgical treatment of native valve endocarditis remains challenging, especially in cases with paravalvular destruction. Basic principles include complete debridement and reconstruction. This study is designed to evaluate the outcomes of surgical reconstruction of complex annular endocarditis using standard techniques and materials, including autologous and bovine pericardium.

Methods: From 1975 to 2000, 358 cases (357 patients, mean age 49 ± 16 years, range 18–88 years) of native valve endocarditis were surgically managed. Bioprosthetic valves were implanted in 189 cases, and mechanical prostheses were implanted in 169 cases. A total of 78 cases of paravalvular destruction were identified: 62 annular abscesses, 8 fistulas, and 8 combined abscesses/fistulas. These were managed with 46 pericardial patches and 32 isolated suture reconstructions after radical debridement and prosthetic valve replacement.

Results: The overall early mortality was 8.4% (n = 30). The mortality with paravalvular destruction was 17.9%, and the mortality with simple leaflet infection was 5.7% (P = .001). The unadjusted survival at 20 years was 26.4% ± 4.9% for bioprosthetic valves and 56.5% ± 8.1% for mechanical prostheses (P = .007). The freedom from recurrent prosthetic valve endocarditis was 78.9% ± 4.4% at 15 years. The freedom from reoperation for recurrent prosthetic valve endocarditis was 85.8% ± 4.2% at 15 years. The freedom from reoperation after reconstruction for paravalvular destruction was 88.2% ± 6.9% at 15 years. The freedom from mortality for recurrent prosthetic valve endocarditis was 92.7% ± 3.4% at 15 years. The independent predictors of reoperation were age (hazard ratio 0.930, P = .005) and intravenous drug use/human immunodeficiency virus plus surgical technique (hazard ratio 12.8, P = .003 for patch reconstruction plus valve and hazard ratio 3.6, P = .038 for valve replacement only). Prosthesis type was not predictive when separated from intravenous drug use/human immunodeficiency virus (hazard ratio 3.268, P = .088).

Conclusion: Paravalvular destruction is associated with a higher operative mortality. Native valve endocarditis can be managed with reasonable long-term survival and low rates of reinfection with radical debridement and pericardial reconstruction with bioprostheses and mechanical prostheses. The type of prosthesis implanted does not influence long-term outcome. Patients with a history of intravenous drug use and human immunodeficiency virus are at increased risk for recurrent infection and reoperation.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
Infectious endocarditis that does not resolve with appropriate antibiotic therapy is a complicated problem associated with substantial morbidity and mortality. Approximately one third of patients with endocarditis will require operative intervention.^1-3 At least 10% of cases of endocarditis develop paravalvular extension associated with the infection, which adds significant morbidity and complexity to the surgery.^4,5

The diagnosis of endocarditis requires a multifaceted approach, including clinical, laboratory, and echocardiographic data. The diagnosis of paravalvular extension is imprecise. The presence of a new atrioventricular conduction block suggests extension, as may persistent bacteremia, recurrent emboli, or a new pathologic murmur. The advent of echocardiography has improved the quality of preoperative evaluation, with the transesophageal approach being significantly more specific and sensitive than the transthoracic imaging for defining extension and abscess.^6,7 Color flow Doppler techniques may demonstrate flow patterns consistent with fistula formation, which is specific for extension.

Operative principles of endocarditis include complete debridement of the infected tissues and drainage of abscess cavities followed by restoration of anatomic relationships, including ventriculo-aortic or atrioventricular continuity. In the majority of cases the infection involves only the valve leaflets; however, in cases with paravalvular destruction, complex repair may be required to close acquired defects and reverse hemodynamic abnormalities.

Multiple surgical options have been advanced for complex reconstruction, and previously the literature has favored homograft reconstruction because of lower recurrent infection rates and the relative ease of complex repair.^8-10 Unfortunately, these grafts are not readily available, especially in urgent and emergency settings.

The objective of this study is to examine the short- and long-term outcomes of surgical reconstruction of complex endocarditis using standard materials, including autologous and bovine pericardium and mechanical and bioprosthetic (BP) valves.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
A retrospective analysis of the prospectively maintained University of British Columbia Cardiac Valve Database from 1975 to 2000 was conducted to identify native valve endocarditis (NVE) cases. Follow-up was conducted periodically through the years with telephone interviews, review of consultative and echocardiographic documentation, and questionnaires to primary care physicians. The University of British Columbia Cardiac Valve Database receives annual renewal from the University of British Columbia Clinical Research Ethics Board, which includes an informed consenting process. A total of 358 cases of endocarditis managed surgically were identified in 357 patients. All operative notes were obtained and re-reviewed to provide details of operative techniques. There were 257 men (72.0%) and 100 women (28.0%). The average age was 48.8 ± 15.9 years (range 18–88 years). The average age was 51.6 ± 17.3 years for those with BP valves and 45.6 ± 13.5 years for those with mechanical prostheses (MPs) (P = .0003, BP > MP). For the major portion of time interval from 1975 to 2000, valve repairs were not included in the University of British Columbia Cardiac Valve Database; consequently, native valve repairs were not included in the study.

Before the mid-1980s, endocarditis was diagnosed by classic clinical criteria, including the combination of positive blood cultures, new or changed murmur, fever, and the presence of progressive heart failure because echocardiography was not available at our institutions before that time.¹¹ More recently, echocardiographic findings have been incorporated as a standard mode for diagnosis. The definitive diagnosis was confirmed by surgical identification of a vegetation or pathologic or bacteriologic diagnosis of the vegetation. Abscess and fistula formation were diagnosed from the surgical description in the operative note. An abscess was defined as a region of necrosis with purulent material creating a cavity within the annulus or surrounding paravalvular tissue in the setting of valvular infection. A fistula was defined as an abnormal communication between 2 cardiac chambers.

If surgical reconstruction after extensive debridement was required, it was defined as complex, requiring either primary suture repair or patch reconstruction using bovine or autologous pericardium. The type of valve used was determined from the database. Follow-up was 96% complete. The average follow-up length was 5.5 ± 5.5 years. The follow-up was 6.1 ± 6.1 years for BP and 4.9 ± 4.5 years for MP (P = .031 BP > MP). Reinfection was defined as endocarditis of the prosthetic valve. Given the large study time period and number of institutions with purged medical records, the documentation of culture results was incomplete.

The details of the patient population are presented in Tables 1 and 2 . The distribution of BP (189) and MP (169) replacements by valve position are as follows: 181 aortic valve replacements (AVRs) (BP 96, MP 85), 107 mitral valve replacements (MVRs) (BP 58, MP 49), 8 tricuspid valve replacement (BP 7, MP 1), and 62 MR (BP 28, MP 34). One patient had 1 MP-AVR and 1 MP-MVR at separate operations. The population included 78 cases (21%) of paravalvular destruction. These included 70 cases of annular abscess or abscess ± fistula and 8 cases of chamber fistula. Table 2 identifies the relationship of abscesses/fistulas by valve position and type of prosthesis used in the reconstruction procedure.

Statistical Analysis
Values are expressed as the mean ± standard deviation unless otherwise indicated. The Kaplan–Meier method was used to determine long-term survival and freedom from reoperation. Quantitative data were compared with an independent samples t test. Comparisons of categoric variables were performed with Fisher's exact test (2 sided), Pearson's chi-square test, or Yates corrected chi-square test as appropriate. An independent statistician performed the analysis.

The risk analysis, univariate and multivariate, was performed to identify the independent predictors of recurrent infection and reoperation for recurrent infection. The risk variables considered were age, gender, valve position, valve type, annular destructive disease, history or presence of IVDU or HIV, and surgical reconstructive technique. Variables with a univariate P value of less than .25 were evaluated in the multivariate modeling.

	Results

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
The overall operative mortality rate for NVE was 8.4% (n = 30). In the cohort with paravalvular destruction (n = 78), the operative mortality was 17.9% (14 AVR, 5; MVR, 4; MR, 5) compared with 5.7% (n = 16) in patients with simple leaflet infection (P = .001). Ninety-eight patients died during follow-up. The overall 10-year survival was 58.2% ± 3.4%. Survival at 15 years was 36.6% ± 4.4% for all patients, and this decreased to 32.6% ± 4.8% by 20 years. The overall predictors of survival were age (hazard ratio [HR] 1.030, P < .001), IVDU/HIV (HR 3.22, P = .00003), and patch + valve reconstruction (HR 2.90, P = .0001).

PVE subsequently developed in 30 patients, with 18 (5.0%) managed with reoperation (Table 3). Of these 30 cases, 7 (23.3%) occurred in patients who had an abscess or fistula at the time of the initial operation (Table 3). Operative mortality for reoperation was 16.6% (3 cases).

Of the 18 reoperative cases, abscess or fistula was present at the initial operation in 3 cases. Of the 12 non-reoperative cases, 8 died and 4 were alive at latest follow-up. Of the 8 deaths (AVR 6, MR 2), 3 AVR had abscess or fistula at the initial operation. Of the 4 alive, non-reoperative cases (AVR 1, MVR 2, MR 1), 1 MR had abscess at the initial operation.

Overall freedom from recurrent infection was 85.8% ± 3.0% at 10 years and 78.9% ± 4.4% at 15 years and 66.9 ± 8.7% at 20 years (Figure 1, A [30/358]). The freedom from recurrent PVE favored MP over BP (P = .027) (Figure 1, B). The freedom from recurrent PVE was not differentiated by the presence or absence of annular destruction (abscess ± fistula) (P = .132) (Figure 1, C). The freedom from reoperation for patients with recurrent PVE was 91.7% ± 2.5% at 10 years, 85.8 ± 4.2% at 15 years, and 72.8% ± 9.3% at 20 years (Figure 2 ). The 10-year freedom from reoperation for annular destruction (abscess ± fistula) was 88.2% ± 6.9% and for pericardial patch reconstruction was 71.5% ± 14.6%. There was 1 reoperation for isolated suture repair of fistula at 209.5 months. The overall freedom from mortality from recurrent PVE (9/30 events) was 95.7% ± 1.5% at 10 years and 92.7% ± 3.4% at 15 and 20 years (Figure 3 ). Of the 3 mortalities from recurrent operative PVE, 1 died 60 days or less after reoperation and 2 died more than 60 days after reoperation.

View larger version (10K): [in this window] [in a new window]   Figure 1. A, Freedom from recurrent PVE (overall). B, Freedom from recurrent PVE (prosthesis type). C, Freedom from recurrent PVE (paravalvular destruction). BP, Bioprosthetic; MP, mechanical prosthesis.

View larger version (8K): [in this window] [in a new window]   Figure 2. Freedom from reoperation for recurrent PVE (overall).

View larger version (7K): [in this window] [in a new window]   Figure 3. Freedom from mortality for recurrent PVE.

Forty-three patients (16.7%) in the overall cohort demonstrated IVDU (40) or were HIV positive (3), and 10 of 43 patients (23.3%) were involved in 55.6% (10/18) of the reinfections requiring reoperation. There were 46 repairs requiring a pericardial patch overall. All 4 patch repairs that ultimately required reoperation were in the IVDU/HIV cohort.

The patient characteristics are presented in Table 1. The univariate predictors for recurrent infection and reoperation for recurrent infection are detailed in Tables 4 and 5 . The univariate predictors for reoperation for recurrent infection are age (HR 0.93, P = .001, protective), valve type BP > MP (HR 4.77, P = .015), IVDU/HIV (HR 11.63, P = .000001), IVDU/HIV plus patch plus valve (HR 35.29, P = .00001), IVDU/HIV plus valve only (HR 7.56, P = .001), and BP plus IVDU/HIV (HR 9.38, P = .0001).

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
The incidence of infective endocarditis is between 1.7 and 6.2 cases per 100,000 person years and is at least 10 times higher in patients with IVDU.¹² The first line of therapy is prolonged intravenous antibiotic therapy with a bactericidal agent or agents. Often surgical referral occurs only after failure of the initial antibiotic therapy. The progressive infection leads to significant valvular and paravalvular destruction causing severe regurgitation and acute heart failure. It is estimated that between 10% and 37% of patients have some paravalvular complication at the time of surgery.^4,13 Twenty-two percent of our cohort had paravalvular involvement.

The surgical treatment of endocarditis is associated with substantial morbidity and mortality. The spread of infection from the valve leaflets to the surrounding tissue causes paravalvular destruction, abscess formation, and fistulization. These complications create a complex surgical problem. The required debridement and subsequent restoration of anatomic continuity can be surgically challenging. In the literature, paravalvular infection is associated with a significantly increased mortality and more frequent recurrent rates.^5,13,14 However, without surgery these patients have a poor outcome, with mortality demonstrated at 100% in 1 study.¹⁵ Our study did not demonstrate any increase in recurrence rates in patients with documented paravalvular destruction versus those with only leaflet involvement at 15 years. However, not unlike other studies, there was a significant difference demonstrated in the operative mortality in patients with paravalvular destruction.

The principles of surgical treatment advocated by our group for the treatment of active endocarditis with paravalvular destruction are based on the premise of complete debridement of the infected tissues and drainage of abscess cavities followed by restoration of anatomic relationships, including ventriculo-aortic or atrioventricular continuity. The extensive defects that result from the complete resection of all infected tissue require complex reconstruction in some cases. Ultimately, we believe that the most important surgical principles are based on radical debridement to eradicate the infection and provide acceptable long-term results. This aggressive approach may be responsible for the improved long-term outcomes seen in our study.

The use of homografts has been advocated as the treatment of choice for multiple reasons.^8,16,17,18 They have flexibility and can be implanted to exclude abscess cavities. Furthermore, the allograft often has a portion of the mitral apparatus attached and provides a larger tissue area. There is an intrinsic resistance to infection reported that is associated with a low rate of recurrent infection. Anticoagulation is not needed as an adjunct after homograft implantation, and therefore the related complications are avoided.

There are, however, several important issues related to homograft use that make other surgical options attractive. Homografts have a rate of structural valve deterioration similar to that of BP valves.¹⁹ They have limited availability in many regions, including Canada. Reoperation on an in situ homograft can be challenging.²⁰

A recent study using homografts by Sabik and colleagues⁸ from the Cleveland Clinic demonstrated similar outcomes despite significant differences in technique, when compared with our results. The 10-year survival in their study was 56% compared with our overall 10-year survival of 58%, and there were no differences in the 10-year freedom from reoperation (96% vs 92%).

A significant proportion (16.7%) of our patient population demonstrated IVDU or were HIV positive. These patients were involved in 55.6% of the reoperations for reinfection and all of the failed patch repairs that were initially performed to repair abscesses or fistulas. This patient cohort challenges available health care principles because of underlying socioeconomic and mental health issues. They often seek medical attention late in the course of the disease process. This may contribute to this cohort having more extensive infections at initial presentation. Their immunocompromised state likely contributes to this. Compliance with long-term antibiotic therapy is poor, and they often continue to use intravenous drugs. Some 73% of this cohort had a BP valve implanted, despite being in general a younger patient group because of concerns related to these factors.

Studies examining which valve is better for implantation in light of endocarditis demonstrate equipoise. Moon and colleagues²¹ found no difference in reinfection rates between BP and mechanical valves. Haydock and colleagues²² compared homografts with standard valves and found no advantage in either group. Lytle and colleagues²⁴ at the Cleveland Clinic also found no difference in rates of reoperation or survival among BP, mechanical, or homograft implantations. A study from the Texas Heart Institute demonstrated an increase in reoperation rates for recurrent endocarditis in patients with BP implantation.²³

Our study demonstrated a significant increase in the rate of reoperation for reinfection by univariate analysis in patients with a BP valve implanted. However, this difference is negated using multivariate logistic regression. This is most likely because of the common practice of implanting BP valves in patients with a known history of IVDU and HIV. This is not an unexpected finding given the known increase risk that this patient population has for endocarditis.¹² Our study did not demonstrate a difference in reinfection rates between mechanical and BP valves in the general population using multivariate analysis.

All of the reoperations for reinfection with the patch closure technique for abscesses and fistulas occurred in patients with IVDU. This suggests that the failures related to this technique are significantly influenced by patient factors. Initial failure to seek attention and more extensive infection processes are common in this group of patients. However, these factors may also be surrogate markers for long-term unreliability with respect to the requirement of prolonged antibiotic therapy and risks of reinfection secondary to ongoing intravenous use.

	Limitations

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
There are limitations to this study. This evaluation is a retrospective review extending over 25 years, and bioprostheses and MPs were used in a region where homografts were not readily accessible. The indications for surgical interventions were based on classic criteria, but acute and chronic phases were incompletely documented. Given the large study time period and number of institutions with purged medical records, the documentation of culture results was incomplete. The exclusion of valve reconstruction/repair is a major limitation of the study. The University of British Columbia Cardiac Valve Database did not completely record valve reconstructions/repair procedures until 2000 when this study was completed. Regardless, given the historical nature of the study, mitral valve repair was not used widely for the majority of the time frame for this study.

	Conclusions

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 
Surgery for infective endocarditis is associated with high morbidity and mortality. Patients are referred often only after they have developed significant and severe regurgitation secondary to valvular and paravalvular destruction. This is associated with a higher operative mortality rate. However, despite the increased complexity of repair required for patients with paravalvular involvement, reasonable long-term survival and low rates of reinfection can be obtained using standard repair techniques if the principle of radical debridement is followed. We demonstrated that standard techniques are as reliable as reported results for homograft repairs. Patients with a history of IVDU and HIV are at increased risk for reinfection and reoperation.

	Acknowledgments

 
The authors extend appreciation to Kevin Shillitto and Florence Chan for work in the preparation of the article.

	Footnotes

 
Presented to the Third Biennial Meeting of the Society for Heart Valve Disease June 17–20, 2005.

	References

Top Abstract Introduction Patients and Methods Results Discussion Limitations Conclusions References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Lynn M. Fedoruk Shahzad S. Karim Samuel V. Lichtenstein Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fedoruk, L. M. Articles by Lichtenstein, S. V. Search for Related Content PubMed Articles by Fedoruk, L. M. Articles by Lichtenstein, S. V. Related Collections Valve disease