HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John M. Stulak Joseph A. Dearani Harold M. Burkhart Rakesh M. Suri Hartzell V. Schaff Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stulak, J. M. Articles by Schaff, H. V. Search for Related Content PubMed PubMed Citation Articles by Stulak, J. M. Articles by Schaff, H. V. Related Collections Valve disease

---

Original Articles: Pediatric Cardiac

The Increasing Use of Mechanical Pulmonary Valve Replacement Over a 40-Year Period

Division of Cardiovascular Surgery, Mayo Clinic and Foundation, Rochester, Minnesota

Accepted for publication July 9, 2010.

^_* Address correspondence to Dr Dearani, Division of Cardiovascular Surgery, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905 (Email: jdearani{at}mayo.edu).

Presented at the Forty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 25–27, 2010.

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Background: Because reoperation is often necessary for bioprostheses, mechanical pulmonary valve replacement (mPVR) may be appropriate for many patients. Mechanical prostheses are durable, but there has been concern concerning valve thrombosis and bleeding complications from warfarin.

Methods: Between October 1965 and August 2008, 54 patients (33 male, median age 30 years, range 5 to 66) underwent mechanical PVR at our institution (40 patients since 2004). Forty-nine of these 54 patients underwent a total of 110 prior operations (median 2, maximum 5), including 89 prior operations on the right ventricular outflow tract (median 1, maximum 4). Diagnoses included congenital (n = 47) and carcinoid (n = 7) heart disease. Bleeding complications were compared with a 1:2 matched patient cohort (age, gender, and diagnosis) receiving bioprosthetic PVR.

Results: The most common concomitant procedures were tricuspid valve replacement in 15 patients, aortic root replacement in 14, and aortic valve replacement in 13. At last follow-up in 45 of 51 early survivors (median 2.2 years, maximum 20 years), there was no perivalvular leak, vegetations, pannus formation, or valve thrombosis. Further, no patient required reoperation on mPVR. Major late bleeding complications occurred in 3 of 54 patients in the mPVR group and 4 of 108 in the tissue PVR group.

Conclusions: Thromboembolic complications are rare with therapeutic international normalized ratios and mechanical PVR provides excellent durability and freedom from reoperation. Tissue PVR does not eliminate bleeding complications. Mechanical PVR should be considered in select patients with multiple prior operations, or when there is another need for warfarin anticoagulation.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Although most of the valve operations performed annually address lesions of the aortic or mitral valves, pulmonary valve replacement (PVR) may be required for pulmonary valve disease. The vast majority of patients, especially children, who require PVR, obtain a tissue valve because of the relative good durability and the lack of a need for anticoagulation. Because the need for repeat operation is inevitable, and the population of adults with congenital heart disease continues to grow, there are increasing situations in which a mechanical pulmonary prosthesis may be appropriate. Most patients being considered for mechanical PVR have a congenital diagnosis and in these complex patients, quality of life and need for further operation are major issues.

Mechanical valves, in general, are durable but require anticoagulation, which carries its own inherent set of risks. There are conflicting reports regarding the late outcome of mechanical prostheses used for PVR. The small body of literature that exists would seem to indicate that, in the pulmonary position, bileaflet valves are at higher risk for complications than monodisc valves, with the quoted failure rate for the St. Jude valve in the pulmonary position approaching 35% [1]. However, the majority of these patients were not anticoagulated with warfarin but simply maintained on aspirin [2–7]. Therefore, our objective was to examine the late results of patients followed at our institution who underwent PVR with a mechanical prosthesis and to compare outcome, need for reoperation, and bleeding complications with a case-matched control cohort who received a bioprosthetic PVR.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
We retrospectively examined our experience between October 1965 and August 2008. During this time there were 2,321 total PVRs at our institution, either a PVR alone or right ventricular to pulmonary artery conduit. We report the clinical characteristics and late follow-up of 54 patients (33 males) who underwent PVR with a mechanical prosthesis; 40 performed since 2004. The median age at operation was 30 years (range 5 to 66 years).

Preoperative cardiac diagnoses are shown in Table 1 and most commonly included bicuspid aortic valve status post Ross procedure in 12 patients (22%), tetralogy of Fallot in 10 (19%), truncus arteriosus in 8 (15%), and carcinoid in 7 (13%). Prior to mechanical PVR, 49 patients previously underwent 110 operations (median 2, maximum 5) (Table 2). This included 47 patients having undergone 89 prior operations on the right ventricular outflow tract (median 1, maximum 4). Six patients had prior implantation of a permanent pacemaker after previous cardiac operations.

Indications for pulmonary valve replacement were stenosis in 19 patients (35%), regurgitation in 17 (31%), and mixed stenosis-regurgitation in 13 (24%). Five patients did not have indications for pulmonary valve replacement per se, but the decision to replace the normally functioning pulmonary bioprosthesis was made after another valve replacement with a mechanical prosthesis in 3 patients, and at the time of primary repair of truncus arteriosus in 2 patients. Concomitant pathology that was present is shown in Table 2, and most commonly included greater than moderate aortic valve regurgitation in 21 patients (39%), greater than moderate tricuspid valve regurgitation in 18 (33%), aortic root aneurysm in 8 (15%), and ascending aortic aneurysm in 6 (11%).

Patients in this cohort were then case-matched 1:2 with patients who received a bioprosthetic PVR during the same time period. Matching criteria were age, gender, and diagnosis (carcinoid or congenital). Median age of the control population was 31 years (p = 0.91), there were 66 males (61%), and 94 (87%) patients had a congenital diagnosis and 14 (13%) had a carcinoid diagnosis.

Statistical Analysis
Demographic and other patient-related data were obtained from Mayo Clinic medical records. Follow-up information was obtained from clinic visits and written correspondence from local physicians. Continuous data were expressed as either mean ± standard deviation or median with a range; categoric data were summarized with frequencies or counts. Early mortality was defined as death occurring within 30 days of operation or any time during the index hospitalization. The Mayo Foundation Institutional Review Board approved this study and all patients or their families gave written informed consent.

	Results

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
All patients underwent implantation of a mechanical valve in the pulmonary position; the valve was part of a RV-PA (right ventricle to pulmonary artery) conduit in 8 patients. Our techniques for isolated mechanical PVR and RV-PA conduit replacement have been described elsewhere [8], and are identical for bioprosthetic valve replacement. In the early years of this study, a tilting-disc valve was implanted in 2 patients and a caged ball prosthesis in 2 patients. A bileaflet mechanical valve is the most common mechanical prosthesis implanted in the current era and has been used in all consecutive patients since 1987. The median size of mechanical prosthesis implanted was 25 mm (range, 21 to 33 mm); the median size of bioprosthetic PVR used in the control group was 27 mm (range 21 to 33 mm). Concomitant procedures performed at the time of mechanical PVR are shown in Table 3 and most commonly include tricuspid valve replacement in 15 patients (28%), aortic root replacement in 14 (26%), and aortic valve replacement in 13 (24%).

Median follow-up in 49 early survivors was 2.2 years, with a range of 3 months to 20 years. The international normalized ratio (INR) was maintained between 2 and 3 in patients with an isolated mechanical pulmonary valve, or in combination with a left-sided mechanical valve, and between 3 and 4 concomitant mechanical tricuspid valve replacement at the time of PVR. All patients were maintained on warfarin; aspirin was administered in conjunction with warfarin in 19 patients.

Actuarial survival for all patients undergoing mechanical PVR was 81% at 5 years; if analyzed according to diagnosis, actuarial 5-year survival was 57% for patients with carcinoid heart disease and 87% for patients with a congenital diagnosis (p = 0.072) (Fig 1). Actuarial 5-year survival for patients receiving mechanical PVR was similar when compared with a 2:1 age-, gender-, and diagnosis-matched cohort of patients undergoing bioprosthetic PVR (81% vs 75%, p = 0.1) (Fig 2). Similarly, in the subset of patients with a congenital diagnosis, survival was not statistically different between patients who underwent mechanical or bioprosthetic PVR (87% vs 86%, p = 0.18) (Fig 3).

View larger version (23K): [in this window] [in a new window]   Fig 1. Overall actuarial survival for patients who have undergone mechanical pulmonary valve replacement is shown (dashed line). Survival curves for patients with carcinoid heart disease (square dots) and congenital heart disease (solid line) are also shown. There was no significant difference in survival according to diagnosis (p = 0.072).

View larger version (23K): [in this window] [in a new window]   Fig 2. Overall actuarial survival curves are shown for patients who have undergone mechanical pulmonary valve replacement (solid line) and bioprosthetic pulmonary valve replacement (square dots). The groups were matched for age, gender, and diagnosis. There was no statistically significant difference between groups (p = 0.1).

View larger version (21K): [in this window] [in a new window]   Fig 3. Overall actuarial survival curves are shown for patients with a congenital diagnosis who have undergone mechanical pulmonary valve replacement (solid line) and bioprosthetic pulmonary valve replacement (square dots). The groups were matched for age and gender. There was no statistically significant difference between groups (p = 0.18).

View larger version (24K): [in this window] [in a new window]   Fig 4. Overall actuarial freedom from reoperation curves are shown for patients who have undergone mechanical pulmonary valve replacement (solid line) and bioprosthetic pulmonary valve replacement (square dots). The groups were matched for age, gender, and diagnosis. There was a statistically significant difference between groups (p = 0.018).

	Comment

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
When patients are adequately anticoagulated with warfarin, we observed no valve thromboses with a mechanical valve in the pulmonary position. Further, with maximum follow-up extending to 20 years, there have been no reoperations on patients in this cohort for pannus formation, paravalvular leak, endocarditis, valve thrombosis, or prosthesis dysfunction.

There has been considerable experience with the use of mechanical prostheses to address left-sided valvular pathology, particularly in the aortic position. These prostheses exhibit excellent durability and offer a long functional life free from complications. However, the issue of performance of a mechanical prosthesis in the pulmonary position is a matter of debate and there are no precise criteria for the selection of patients in whom this prosthesis would be well suited.

Valve replacement in children with congential heart disease represents a challenging situation that demands special considerations due to the complex characteristics of this patient population. Prostheses should be durable and should offer potential for avoiding patient-valve mismatch due to outgrowth. The issue of anticoagulation in this patient population also weighs into the decision of which prosthesis to use, as this has been claimed to carry a risk in these young, active patients.

In general, most authors recommend the use of bioprosthetic valves for pulmonary valve replacement in young patients who undergo surgery for congenital heart lesions [2]. The range of reported thrombotic complications for a mechanical pulmonary valve in the literature is from 25% to 80% [2–7, 9]. According to the small body of literature that exists on the topic, complications occur predominantly in patients with bileaflet valves while no complications have been reported for tilting disc valves in the pulmonary position; the complication rate of a bileaflet valve in the pulmonary position has been reported to be approximately 35% [1]. Careful analysis of this literature, however, demonstrates that the majority of thromboses were observed in patients who were not anticoagulated with warfarin but simply maintained on aspirin (Table 4). Taken together, if patients were not maintained on warfarin, the frequency of thrombosis for a bileaflet valve in the pulmonary position was 41% (15 of 37 valves failed). Including the present study, when patients were adequately anticoagulated with warfarin, the valve thrombosis rate of mechanical valves in the pulmonary position was 3.5% (Table 5) [9–12]. In addition, one of the three documented failures of the bileaflet valves in the anticoagulated patients occurred when the INR was found to be in the subtherapeutic range [10]. Although there was initial hope that no anticoagulation would be required with this valve, this is not the case. There is a documented increased rate of embolic and thrombotic valve complications with inadequate or no anticoagulation [13, 14].

As the number of adults with repaired congenital heart disease increases, the need for one or more reoperations is inevitable. As adults with congenital heart disease come to require numerous subsequent reoperations, the operative risk of mortality increases from 2.0% at the first repeat sternotomy compared with 4.7% at a fourth time resternotomy [17]. Furthermore, Morashita and colleagues [18] demonstrated a fourth time sternotomy to be a predictor of resternotomy-related injury (OR = 4.31). In these patients who present for operation after having had multiple prior sternotomies, a mechanical valve may represent a more durable solution and may help avoid future reoperations. This likely represents the largest population of patients in whom a mechanical valve should be considered. Another important patient population is those with carcinoid heart disease. In general, we recommend the use of a tissue valve in these patients because of the likelihood they will need to undergo interventions for their carcinoid disease (ie, liver resection, embolization, etc). Avoiding warfarin anticoagulation in this situation simplifies future potential procedural management. However, if the patient has a smaller burden of hepatic disease and their symptoms are controlled with octreotide, we would consider a mechanical valve, because this patient has a longer expected survival. In every case that a mechanical valve is considered, the ultimate treatment decision is individualized after weighing the risks of reoperation if a tissue valve is chosen with potential bleeding risks from anticoagulation if a mechanical valve is chosen.

There are several advances that may decrease the future risk of anticoagulant-related bleeding. The first is realization that the current practice of aggressive anticoagulation in these patients is based on older data of these prostheses in the pulmonary position, and perhaps these patients do not require such high levels of anticoagulation. Our practice is to target these patients' INR at 3. In patients who received a concomitant mechanical tricuspid valve prosthesis the target INR is 3.5. There are data demonstrating the safety of lower intensity of anticoagulation for bileaflet mechanical aortic prostheses [19]. These results may be able to be extrapolated to bileaflet mechanical valves in the pulmonary position. The second is the availability of new antiplatelet agents and direct thrombin inhibitors which have a consistent pharmacology, wider therapeutic window, and fixed dose. The side-effect profile of these medications is much less than that of warfarin [20]. The third is patient INR self-testing. Horstkotte and Piper [21] have demonstrated a significant decrease in bleeding complications from 10.9% with usual care to 4.5% with self-testing. This decrease in bleeding risk was not accompanied by an increase in the rate of thromboembolism (usual care 3.6% vs self-testing 0.9%). These results are directly related to patients spending significantly more time in the therapeutic range, with less fluctuations in INR values (usual care 50% vs self-testing 89%) [22].

In summary, our series demonstrates a low risk of mechanical pulmonary valve thrombosis and prosthetic valve failure when patients are adequately anticoagulated [23]. Because the majority of patients in this series had operation after 2004, the median follow-up was 2.2 years; however, the data suggest that a mechanical prosthesis in the pulmonary position provides excellent durability and hemodynamics, similar to its performance in the aortic position. The performance of these prostheses in the pulmonary position may help patients with numerous prior operations avoid future reoperations, each of which may decrease quality of life and add significant risk as the number of repeat operations increases. Despite these findings, the message of this paper is not that these prostheses should be used liberally, but rather, it is reasonable to consider in highly selected circumstances. The decision to insert a mechanical prosthesis in order to obtain longer durability when compared with a tissue valve must also be considered in the context of evolving techniques of percutaneous pulmonary valve replacement, which may also spare or prolong the time period to the next reoperation. As such, we consider a mechanical prosthesis for pulmonary valve replacement in highly selected adult patients who have had multiple prior operations, those who require anticoagulation for other reasons, or patients who have demonstrated accelerated deterioration of a previously placed tissue prosthesis. Finally, improved anticoagulation monitoring and future alternative anticoagulation options will further reduce the risks of bleeding and thromboembolism, making mechanical PVR a potentially more attractive option for some patients.

	Discussion

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
DR JOSEPH FORBESS (Dallas, TX): The first question I would ask is when you say that you have 14 patients that had aortic root replacements, was that a valve-sparing root replacement or a composite where you replaced the aortic valve as well?

DR STULAK: Patients in this series that underwent aortic root replacement received an aortic valve replacement as part of a composite graft.

DR FORBESS: So then 27 patients actually got?

DR STULAK: Correct.

DR MARSHALL JACOBS (Cleveland, OH): Dr Stulak, I want to compliment you on a nice analysis and a very elegant presentation.

My question goes to your thoughts about anticoagulation and prosthetic pulmonary valves. I'm guessing that the anticoagulant regimen prescribed for these patients was most often determined by some factor other than the presence of the pulmonary valve prosthesis. As you said, the mechanical prostheses were used either in the setting of another mechanical valve or another indication for anticoagulation. So, the freedom from thrombotic events is very satisfying, and somewhat reassuring, but not terribly surprising since these were aggressively or therapeutically anticoagulated patients. What are the factors that you think influence ultimate anticoagulation goals for a pulmonary prosthesis in isolation? What are your thoughts about lower levels of INR [international normalized ratio] in patients who are being treated primarily for the pulmonary prosthesis and not for other indications?

DR STULAK: Thank you, Dr Jacobs. I am honored to receive a question from you.

In terms of anticoagulation, because not many mechanical valves are implanted in the pulmonary position, there is not an abundance of solid data to guide us. Our algorithm is as follows: for an isolated mechanical pulmonary prostheses, the goal INR is between 2.5 and 3.5; if a concomitant mechanical tricuspid prosthesis is implanted, the goal INR is between 3.5 and 4.5. However, exactly as you indicated, maybe the goal INR is so high because of historical concern of thrombosis. Perhaps the goal INR does not need to be that high. Further, if the goal INR were lowered, perhaps it would decrease the bleeding risk and thus make this a more attractive option for patients.

DR HITENDU H. DAVE (Zurich, Switzerland): It was a nice presentation, and I think we do sometimes face this issue when a patient comes after multiple prior sternotomies. But I'm really perplexed at a couple of things. One of them is you said that you would prophylactically remove a functioning valve when the patient has any other valve. I don't think that the risk is the same when you have two prostheses as compared to one. And I feel a little uneasy about this recommendation.

And the second issue was about your idea that bioprostheses have bleeding complications and they end up with anticoagulation. We, for one, have not really seen such difficult problems with [a] pulmonary bioprosthesis. Since at a follow-up of 2 to 3 years you've got one bleeding or embolism complication in this patient population who are probably in their 30s or 40s, one may expect to have much more during their remaining life span. Can you explain that?

DR STULAK: Just to be clear, we are not recommending the exchange of a normally functioning bioprosthesis with a mechanical one. That was done in 3 of these patients because the patients, respectively, had 3 and 4 prior sternotomies. So if a mechanical aortic valve is going to be inserted, and the goal is to avoid future resternotomies, then maybe consideration can be given to replacing a normally functioning bioprosthesis in the pulmonary position. This was done at the discretion of the operating surgeon at the time in a minority of patients in this series; however, it may be a scenario that is faced in a patient, and it may be a consideration.

In terms of bleeding complications, when patients receive tissue valves, a percentage of patients, albeit small, will end up on warfarin anticoagulation for other reasons; for example, if they have a pulmonary embolus or have atrial fibrillation. The point is that bleeding complications can occur even when a bioprosthesis is utilized; even patients that take aspirin can have GI [gastrointestinal] bleeds, so any anticoagulation is not benign. Patients in the matched cohort with bioprostheses in this series did have a trend toward lower bleeding complications, but they still had some bleeding events.

DR N. ROY (Vancouver, British Columbia): I have two questions for you. Would you be able to comment on the postoperative gradients that you observed, and is there a minimum size of prosthesis that you would or would not consider for those reasons?

And the second question. In a clinical situation where the right ventricular function is marginal, and Ebstein's anomaly is an example, would that make you decide against such a prosthesis?

DR STULAK: The size of prosthesis is based on the size of the aortic annulus and then upsized by one. Usually in the adult this ends up being a 25 or 27 mm mechanical valve. If a patient has altered ventricular function, we would actually upsize it even more. Usually the gradients are in the 4 to 5 mm Hg range after a mechanical prosthesis is implanted in the pulmonary position. We routinely perform direct needle measurements after valve insertion and discontinuation from cardiopulmonary bypass.

	References

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 

1. Rosti L, Murzi B, Colli AM, et al. Mechanical valves in the pulmonary position: A reappraisal J Thorac Cardiovasc Surg 1998;115:1074-1079.[Abstract/Free Full Text]
2. Ilbawi MN, Lockhart CG, Idriss FS, et al. Experience with St. Jude Medical valve prosthesis in children: a word of caution regarding right-sided placement. J Thorac Cardiovasc Surg 1987;93:73-79.[Abstract]
3. Ilbawi MN, Lockhart CG, Idriss FS, et al. Valve replacement in children: guidelines for selection of prosthesis and timing of surgical intervention Ann Thorac Surg 1987;44:398-403.[Abstract/Free Full Text]
4. Kiyota Y, Shiroyama T, Akamatsu T, Yokota DY, Ban T. In vitro closing behavior of the St. Jude Medical heart valve in the pulmonary position: valve incompetence originating from the prosthesis itself. J Thorac Cardiovasc Surg 1992;104:779-785.[Abstract]
5. Burger W, Kneissl GD, Hartmann A, et al. Successful thrombolysis after prosthetic pulmonary valve obstruction under aspirin monotherapy Ann Thorac Surg 1997;64:255-258.[Abstract/Free Full Text]
6. Nurozler F, Bradley S. St. Jude Medical valve in pulmonary position: Anticoagulation and thrombosis. Asian Cardiovasc Thorac Ann 2002;10:181-183.[Abstract/Free Full Text]
7. Pass HI, Sade RM, Crawford FA, Hohn AR. Cardiac valve prostheses in children without anticoagulation J Thorac Cardiovasc Surg 1984;87:832-835.[Abstract]
8. Stulak JM, Dearani JA. Technique of mechanical pulmonary valve replacement Operative Techniques in Thoracic and Cardiovascular Surgery 2006;11:200-206.
9. Miyamura H, Kanazawa H, Hayashi J, Eguchi S. Thrombosed St. Jude valve prosthesis on the right side of the heart in patients with tetralogy of Fallot. J Thorac Cardiovasc Surg 1987;94:148-150.[Abstract]
10. Kawachi Y, Masuda M, Tominaga R, Tokunaga K. Comparative study between St. Jude Medical and bioprosthetic valves in the right side of the heart. Jpn Circ J 1991;55:553-562.[Medline]
11. Konstantinov IE, Peterffy A. Tricuspid and pulmonary valve replacement in carcinoid heart disease: two case reports and a review of the literature J Heart Valve Dis 1997;6:193-197.[Medline]
12. Haas F, Schreiber C, Horer J, Kostolny M, Holper K, Lange R. Is there a role for mechanical valved conduits in the pulmonary position? Ann Thorac Surg 2005;79:1662-1667discussion 1667–8.[Abstract/Free Full Text]
13. Baudet EM, Oca CC, Roques XF, et al. A 5- year experience with St. Jude Medical cardiac valve prosthesis: Early and late results of 737 valve replacements in 671 patients J Thorac Cardiovasc Surg 1985;90:137-144.[Abstract]
14. Czer LS, Matloff J, Chaux A, DeRobertis M, Yoganathan A, Gray RJ. A 6-year experience with the St. Jude Medical valve: Hemodynamic performance, surgical results, biocompatibility, and follow-up. J Am Coll Cardiol 1985;6:904-912.[Medline]
15. Bando K, Danielson GK, Schaff HV, Mair DD, Julsrud PR, Puga FJ. Outcome of pulmonary and aortic homografts for right ventricular outflow tract reconstruction J Thorac Cardiovasc Surg 1995;109:509-518.[Abstract/Free Full Text]
16. Cleveland DC, Williams WG, Razzouk AJ, et al. Failure of cryopreserved valved conduits in the pulmonary circulation Circulation 1992;86(5 suppl):II150-II153.[Medline]
17. Brown ML, Dearani JA, Burkhart HM. The adult with congenital heart disease: medical and surgical considerations for management Curr Opin Pediatr 2009;21:561-564.[Medline]
18. Morishita K, Kawaharada N, Fukada J, et al. Three or more median sternotomies for patients with valve disease: role of computed tomography Ann Thorac Surg 2003;75:1476-1480.[Abstract/Free Full Text]
19. García-Rinaldi R, Carro-Pagán C, Schaff HV, et al. Initial experience with dual antiplatelet thromboprophylaxis using clopidogrel and aspirin in patients with mechanical aortic prostheses J Heart Valve Dis 2009;18:617-625.[Medline]
20. Squizzato A, Dentali F, Steidl L, Ageno W. New direct thrombin inhibitors Intern Emerg Med 2009;4:479-484.[Medline]
21. Horstkotte D, Piper C. Improvement of oral anticoagulation therapy by INR self-management J Heart Valve Dis 2004;13:335-338.[Medline]
22. Lafata JE, Martin SA, Kaatz S, Ward RE. The cost-effectiveness of different management strategies for patients on chronic warfarin therapy J Gen Intern Med 2000;15:31-37.[Medline]
23. Bonow RO, Carabello B, de Leon Jr AC, et al. Guidelines for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation 1998;98:1949-1984.[Free Full Text]

This article has been cited by other articles:

				H. J. Shin, Y.-H. Kim, J.-K. Ko, I.-S. Park, and D. M. Seo Outcomes of Mechanical Valves in the Pulmonic Position in Patients With Congenital Heart Disease Over a 20-Year Period Ann. Thorac. Surg., April 1, 2013; 95(4): 1367 - 1371. [Abstract] [Full Text] [PDF]

				C. Lee, C.-H. Lee, J. G. Kwak, J. Y. Song, W.-S. Shim, E. Y. Choi, S. Y. Lee, and Y. M. Kim Bicuspid pulmonary valve implantation using polytetrafluoroethylene membrane: early results and assessment of the valve function by magnetic resonance imaging Eur J Cardiothorac Surg, March 1, 2013; 43(3): 468 - 472. [Abstract] [Full Text] [PDF]

				T. Miyazaki, M. Yamagishi, Y. Maeda, Y. Yamamoto, S. Taniguchi, Y. Sasaki, and H. Yaku Expanded polytetrafluoroethylene conduits and patches with bulging sinuses and fan-shaped valves in right ventricular outflow tract reconstruction: Multicenter study in Japan J. Thorac. Cardiovasc. Surg., November 1, 2011; 142(5): 1122 - 1129. [Abstract] [Full Text] [PDF]

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 Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John M. Stulak Joseph A. Dearani Harold M. Burkhart Rakesh M. Suri Hartzell V. Schaff Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stulak, J. M. Articles by Schaff, H. V. Search for Related Content PubMed PubMed Citation Articles by Stulak, J. M. Articles by Schaff, H. V. Related Collections Valve disease