Ann Thorac Surg 2006;82:2123-2132
© 2006 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
What Prosthesis Should Be Used at Valve Re-Replacement After Structural Valve Deterioration of a Bioprosthesis?
Lawrence Lau, MBBS Honsa,
W.R. Eric Jamieson, MDb,*,
Clifford Hughes, FRACSa,
Eva Germann, MSb,
Florence Chanb
a University of Sydney, Sydney, Australia
b University of British Columbia, Vancouver, Canada
Accepted for publication July 13, 2006.
* Address correspondence to Dr Jamieson, 486 Burrard Building, St. Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6 (Email: wrej{at}interchange.ubc.ca).
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Abstract
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BACKGROUND: The fate of bioprostheses (BP) and mechanical prostheses (MP) after valve re-replacement for bioprostheses is not well-documented. This research compares the late fate of these two valve types after valve re-replacement for structural valve deterioration (SVD) of a bioprosthesis.
METHODS: Between 1975 and 2000, 298 patients had successful aortic valve re-replacements (AVRR) (BP n = 149, average age = 67.1 ± 12.3 years; MP 149, 58.9 ± 10.9) and 442 patients had successful mitral valve re-replacements (MVRR) (BP 155, 65.8 ± 14.1; MP 287, 60.8 ± 11.7) after SVD of a previous BP. Follow-up was five years in all groups.
RESULTS: (1) Aortic position (AVRR): Survival favored MP over BP overall, at 10 years (70.3 ± 5.4% vs 56.7 ± 5.7%, p = 0.0220). This survival advantage was seen to be significant only in patients less than 60 years of age (at 10 years, 85.3 ± 4.9% vs 59.2 ± 9.8%, p = 0.038). No significant difference in survival between the two valve types was observed in patient age groups greater than 60 years of age. Freedoms from valve-specific complications, including reoperation for SVD-thrombosis, major thromboembolism and hemorrhage, and valve-related mortality were not significantly different between the two groups overall. (2) Mitral position (MVRR): Survival favored MP over BP overall (58.6 ± 4.2% vs 42.1 ± 5.2%, p = 0.0011), and in patients greater than 70 years of age (32.8 ± 8.9% vs 16.7 ± 7.1%, p = 0.008). Freedoms from valve-specific complications and valve-related mortality favored MP over BP.
CONCLUSIONS: There was no clinical performance difference between mechanical and bioprosthetic valves in patients greater than 60 years of age upon AVRR. Mechanical valves generally outperformed bioprosthetic valves in all age groups in MVRR.
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Introduction
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Reoperation for structural valve deterioration of bioprostheses is an increasingly frequent indication for surgery due to increasing valve replacement operations and increasing long-term survival of patients. It is therefore important to have valid clinical protocols for valve reoperation.
There is extensive literature comparing the performances of mechanical and bioprosthetic valves [1–6]. Mechanical valves are thrombogenic so that patients require indefinite anticoagulation thereby predisposing to hemorrhagic complications [1–6]. Bioprostheses, on the other hand, have limited durability and the risks of reoperation are considerable [1–9]. At valve replacement surgery, the risks of bioprosthetic valves are weighed against those of mechanical valves.
Upon reoperation, other considerations arise, such as whether a structurally failed bioprosthetic valve is a contraindication for another, and whether a second bioprosthesis will outlast the life expectancy of an elderly patient. The risks and early consequences of reoperation after valve deterioration of bioprosthetic valves were reported previously in two studies that assessed reoperation in the aortic and mitral positions [8, 9]. Late performances of mechanical and bioprosthetic valves after reoperation have yet to be adequately addressed in current literature.
The purpose of this report is to determine the long-term fate of bioprosthetic and mechanical valves in different age groups after reoperation for structural failure of a previously inserted bioprosthetic valve. This will provide information to assist the surgeon to choose the best prosthesis in this particular situation.
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Patients and Methods
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This is a retrospective study of prospectively collected data from the University of British Columbia Cardiac Valve Database. The database has received annual renewal from the University of British Columbia Research Ethics Board, which has a formal consenting process of patients. It includes all patients who had a single valve re-replacement (second operation) for structural valve deterioration (SVD) of a bioprosthetic valve at the University of British Columbia between 1975 and 2000. There were 481 mitral re-replacements. In the corresponding aortic population, 322 re-replacements were performed. Patients having multiple replacements, patients undergoing their second (or further) valve re-replacement (third or more operation), and patients who did not survive re-replacement surgery were excluded from this study.
The end points compared were survival and major valve-related complications, including structural valve deterioration, thromboembolism, and hemorrhage, further reoperation, and valve-related mortality. The "Guidelines for Reporting Morbidity and Mortality After Cardiac Valvular Operations" [10] was used to define the complications.
Actuarial analyses of survival were performed by the Kaplan-Meier method and are presented with standard error of the estimate. Actuarial curves were compared using the log-rank statistical test where p values less than 0.05 are considered significant. For the other end points, both actual as well as actuarial analyses were used. It should be noted that it is not appropriate to statistically compare actual curves.
Follow-up was for an average of 5.2 ± 4.6 (bioprostheses) and 5.9 ± 3.6 (mechanical prostheses) years after aortic reoperation and 4.8 ± 5.0 (bioprostheses) and 5.8 ± 3.8 (mechanical prostheses) years after mitral reoperation. Follow-up was 98.5% complete.
Cardiac rhythm was documented before the re-replacement for SVD and(or) after the re-replacement for SVD, whether the patient received a mechanical prosthesis or bioprosthesis. The antithrombotic medication, whether anticoagulation or antiplatelet therapy, was documented after the reoperation for SVD. All mechanical prostheses patients were expected to be on anticoagulation management. Prior to 1989, the aortic bioprosthesis replacement patients were generally managed with anticoagulation up to 3 months if they were in sinus rhythm and continually if they were in atrial fibrillation or had other risk factors for thromboembolism. After 1989, our practice gradually changed with the use of only antiplatelet therapy for aortic bioprostheses if the cardiac rhythm was that of sinus. The combination of anticoagulant and antiplatelet therapy was not generally used. The international normalized ratio (INR) target range in current years was aortic 2.2 to 3.2, while for mitral the range was 2.5 to 3.5. Prior to the current era, when the INR methodology was introduced into North America, the target range was 2.5 to 4.5 generally without different targets for aortic and mitral mechanical prostheses.
In the aortic position, there were 322 re-replacements of whom, 298 patients survived (7.4% operative mortality). In the mitral position, there were 481 re-replacements with an operative mortality of 8.1% so that 442 patients in this group were studied. Operative mortality is defined as death occurring within 30 days of operation [10].
Of the 298 aortic re-replacement survivors, half received a bioprosthetic valve and their average age was 67.1 ± 12.3 years. The other half, with mechanical valves, had an average age of 58.9 ± 10.9 years. The 155 mitral valve re-replacement survivors who received bioprosthetic valves had an average age of 65.8 ± 14.1 years. The remaining 287 mitral re-replacement survivors with mechanical valves had an average age of 60.8 ± 11.7 years. As patient ages were significantly different between mechanical and bioprosthetic valves in both positions (p values < 0.001), the patient groups were separated into four age groups (Table 1).
In the aortic group, there was no statistical significance in gender with 74% and 76% males in the bioprosthetic and mechanical cohorts, respectively. There was no significant gender difference in the mitral group either, as 33% and 29% of the bioprosthetic and mechanical patients were men.
The number and types of different valves utilized in this study are shown in Appendix 1. Of the valves used, 92% of mechanical valves and 83% of the bioprostheses were contemporary prostheses.
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Results
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After Aortic Valve Re-Replacement
Survival
The late survivals after aortic valve reoperation were compared by actuarial analysis. Overall, mechanical prostheses were associated with a significantly greater survival (p = 0.0220) (Fig 1). This was most striking in patients less than 60 years of age, with mechanical valves conferring a survival of 85.3 ± 4.9% versus 59.2 ± 9.8% with bioprosthetic valves (p = 0.038). The other age groups did not show any significant difference between the two valve types. In patients greater than 70 years, the survival at 10 years in patients with bioprostheses was 53.1 ± 9.0% compared with 27.2 ± 14.3% with mechanical prostheses (p value not significant) (Fig 2). Comparisons of survival at 10 years in the different age groups are shown in Appendix 2.
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Fig 1. Survival after aortic valve re-replacement patients overall. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Fig 2. Survival after aortic valve re-replacement patients greater than 70 years of age. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Valve-related mortality
In the entire aortic cohort, actual freedom from death attributable directly to the inserted valve was not significantly different (actuarial p = 0.7006) at 10 years between mechanical and bioprosthetic valves (95.0 ± 2.2% vs 96.6 ± 2.0%) (Appendix 2). For patients greater than 70 years, those with bioprosthetic valves had an actual freedom from valve-related mortality of 98.0 ± 1.9% compared with those with mechanical valves who had a freedom of 85.7 ± 9.4% (actuarial p = 0.099, not significant).
Subsequent reoperation
Not surprisingly, there was greater freedom from further valve-related reoperation among patients with mechanical valves than those with bioprosthetic valves overall (actual freedom at 10 years, 96.9 ± 1.5% vs 85.0 ± 4.0%, actuarial p value = 0.0032). As expected, there was no significant difference in the freedoms from further aortic valve reoperations in patients greater than 70 years as these patients seldom undergo reoperative procedures (Appendix 2).
Valve-related complications
Freedom from valve-related complications, including structural deterioration, all events of thromboembolism and bleeding, nonstructural dysfunction, prosthetic valve endocarditis, and thrombosis were analyzed. Overall and in all age groups, there was no significant difference in freedom from such complications between the two valve types (Appendix 2). In patients greater than 70 years of age, those with bioprosthetic valves had an actual freedom of 83.2 ± 5.1% versus 65.7 ± 12.5% in patients with mechanical valves (actuarial p value not significant).
Major valve-specific complications
Structural valve deterioration and the subsequent risks of reoperation are the major complications associated with bioprosthetic valves while thrombosis, thromboembolism, and hemorrhagic events are the major complications after implantation with mechanical valves. It was therefore decided to assess the performance of mechanical and bioprosthetic valves by comparing their freedoms from major valve-specific complications including structural deterioration and thrombosis leading to further reoperation and major events of thromboembolism and hemorrhage.
There was no incidence of either thrombosis with bioprosthetic valves or structural deterioration with mechanical valves in this study. Overall (Fig 3), and in patients less than 60 years of age, the freedoms from major valve-specific complications were not different (Appendix 2). In patients between 60 and 65 years of age, actual analysis showed mechanical valves to have a freedom from these major complications of 84.4 ± 7.3% compared with bioprostheses with a freedom of 57.5 ± 21.0% (actuarial p value not significant). For patients between 65 and 69 years of age, the freedoms exhibited by mechanical and bioprosthetic valves were 84.7 ± 8.4% and 60.8 ± 13.4%, respectively (actuarial p value not significant). In patients greater than the age of 70 years, the actual freedom from major valve-specific complications for mechanical valves at 10 years was 79.0 ± 10.8% while for bioprosthetic valves, it was 90.8 ± 3.9% (actuarial p value not significant) (Fig 4).
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Fig 3. Freedom (actual) from major valve-specific complications after aortic valve re-replacement in patients overall. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Fig 4. Freedom (actual) from major valve-specific complications after aortic valve re-replacement in patients greater than 70 years of age. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Major thromboembolism and hemorrhage
Major thromboembolic and hemorrhagic events include the following: any thrombus interfering with the function of the valve, any cerebrovascular event lasting greater than 24 hours, peripheral embolic events, and any major internal or external bleeding that causes death, hospitalization, permanent injury, or requires transfusion. There was no significant difference between bioprosthetic and mechanical valves overall (Appendix 2). There was also no significant difference between the two valve types in all age groups except for patients less than 60 years, where those with bioprosthetic valves enjoyed a 100% actual freedom from major thromboembolic and hemorrhagic complications compared with 80.8 ± 5.3% of those who had mechanical valves (actuarial p value = 0.015).
After Mitral Valve Re-replacement
Survival
In the whole mitral cohort, survival of patients implanted with a mechanical valve upon mitral valve re-replacement was significantly greater (actuarial p value = 0.0011) than those implanted with bioprosthetic valves (Fig 5). The 10-year survival of patients with mechanical valves was 58.6 ± 4.2% and of patients with bioprosthetic valves, 42.1 ± 5.2% (Appendix 3). Mechanical valves were observed to convey significantly better survival in the mitral position than bioprosthetic valves in the greater than 70 years age group (Fig 6). For patients less than 70 years of age, the survival trend was not statistically different between biological and mechanical valves (Appendix 3).
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Fig 5. Survival after mitral valve re-replacement patients overall. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Fig 6. Survival after mitral valve re-replacement patients greater than 70 years of age. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Valve-related mortality
Overall actual freedom from valve-related mortality for bioprosthetic valves was 86.3 ± 3.8% compared with 92.9 ± 2.1% for mechanical valves at 10 years (actuarial p value = 0.0956, not significant). The freedoms when separated into different age groups were not significant (Appendix 3).
Subsequent reoperation
Freedom from subsequent mitral valve reoperation was significantly greater for patients with mechanical prostheses when compared with patients with bioprostheses (Appendix 3) but no significant difference was observed between the two valve types in patients greater than 70 years.
Valve-related complications overall
Freedom from all valve-related complications was significantly greater in the patient population with mechanical valves (actuarial p value = 0.0001). The advantage of mechanical valves with respect to freedom from all valve complications in the age groups was observed to be significant only in patients less than 60 years (Appendix 3). Mechanical prostheses had a slight advantage over bioprostheses in patients greater than 70 years of age although this did not reach statistical significance (actual 67.2 ± 7.3% vs 56.6 ± 8.0%, actuarial p value = 0.0508).
Major valve-specific complications
In patient groups less than 70 years, freedoms from major valve-specific complications were significantly greater in those with mechanical valves (p values < 0.005) (Appendix 3; Fig 7). Mechanical valves also outperformed bioprosthetic valves in patients greater than 70 years but this did not reach statistical significance (p value = 0.0562) (Fig 8).
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Fig 7. Freedom (actual) from major valve-specific complications after mitral valve re-replacement in patients overall. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Fig 8. Freedom (actual) from major valve-specific complications after mitral valve re-replacement in patients greater than 70 years of age. (— = bioprostheses [BP]; – – – = mechanical prostheses [MP].)
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Major thromboembolism and hemorrhage
Overall freedom from major thromboembolism and hemorrhage was not different between bioprosthetic and mechanical valves. In the youngest group of patients, those less than 60 years of age, bioprosthetic valves performed significantly better with an actual freedom of 94.1 ± 4.0% compared with the mechanical valve freedom of 86.4 ± 3.7% (actuarial p value = 0.0458). There was no significant difference between the two valve types in the other age groups (Appendix 3).
Antithrombotic management
Atrial fibrillation was identified in 28.2% (42) for AVRR bioprostheses (BP), 56.8% (88) for MVRR BP, 31.5% (47) for AVRR mechanical prostheses (MP) and 67.6% (194) for MVRR MP. The follow-up evaluations revealed that of the AVRR BP, 25.5% (38) were on anticoagulation therapy (AC) and 50.3% (75) were on antiplatelet therapy (AP); of the AVRR MP, 90.6% (135) AC and 0% AP. Of the MVRR BP, 50.3% (78) AC and 20.0% (31) AP and of the MVRR MP, 84.7% (243) AC and 2.4% (7) AP. The incomplete documentation is due to unrecorded data or lack of antithrombotic medications.
Summary of Comparative Performance
Table 2
provides a comparative summary of aortic valve re-replacement (AVRR) and mechanical valve re-replacement (MVRR) for survival and major valve-specific complications for each population overall and by age groups within that population. This table affords a summary of the results of the study, specifically for survival and freedom from major valve-specific complications within AVRR and MVRR for each overall population and subsets thereof.
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Comment
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Currently, fate after valve re-replacement has not been well-documented. Therefore, decisions as to which valve type to implant at this second operation is dictated by influence from studies following primary valve replacements. This study looks specifically at late results after valve re-replacements.
Bioprostheses have been shown to be decent valvular substitutes that allow patients to maintain a good quality of life, as they do not generally require continuous anticoagulation medication, unlike mechanical prostheses. However, bioprostheses come with the threat of SVD and the imminent risk of reoperation whereas mechanical prostheses are much more durable and rarely fail structurally. Thus, the question is do the dangers of continuous anticoagulation outweigh those of structural valve deterioration?
At the time of a second replacement, other questions need to be answered. Does older age affect the risk of SVD? Are bioprosthetic and mechanical valve performances after valve re-replacement the same as their performances after the initial replacement? Is a previous structurally failed bioprosthetic valve a contraindication for another one? Will a second bioprosthetic valve outlast the life expectancy of an elderly patient?
In a previous study by Jamieson and colleagues [11], increased patient age was found to be a major predictor of, and inversely related to, SVD. This is most likely due to decreased hemodynamic stress on the valve with increasing age. This inverse relationship between age and structural deterioration of bioprosthetic valves is also reflected in our series. We noted an increase in the freedom from further reoperations with increasing age at re-replacement in both aortic and mitral positions. Holper and colleagues [3] advise that the durability of mechanical valves, compared with bioprosthetic valves, is not necessarily an advantage in patients 65 years and older. They recorded no difference in freedom from reoperation between patients in this age group with mechanical and bioprostheses perhaps because of the limited number of patients exposed to the onset of bioprosthetic structural failure. Similarly, in our study, while mechanical valves had significantly greater freedom than bioprosthetic valves from further reoperation in patients between 65 and 70 years in the aortic position, there was no difference in patients greater than 70 years of age in both aortic and mitral positions.
Bioprosthetic valves in the aortic position have significantly greater durability than in the mitral position [11] most likely due to less hemodynamic stress in the aortic position. The difference in freedoms from failure between aortic and mitral prosthetic valves is important to consider by patients upon valve selection.
The 10-year survivals in all patients with bioprosthetic valves at valve re-replacement in our study were similar to the 10-year survivals of patients implanted with bioprosthetic valves at initial valve replacement in a study by Fradet and colleagues [5]. These authors looked at the Carpentier-Edwards standard porcine bioprosthesis (57.8% 10-year survival) and the Carpentier-Edwards supra-annular porcine bioprosthesis (53.8% 10-year survival). Our 10-year bioprosthetic patient survivals after re-replacement were also similar to the 10-year bioprosthetic patient survival observed by Hammermeister and colleagues [1] after initial valve replacement.
Interestingly, patients with mechanical valves implanted after the deterioration of a bioprosthetic valve in our study had a better 10-year survival compared with patients who had a mechanical valve implanted to replace a failed natural valve, as observed in a number of other studies [1, 5, 12]. Ikonomidis and colleagues [13] reported a 57% 10-year survival for patients who received a St. Jude Medical mechanical prosthesis upon aortic valve replacement. This survival was less than the 70.3% 10-year survival observed by patients who received mechanical valves upon aortic valve re-replacement in this study. The reason for this is unclear and may be due to differing patient selection criteria. Further investigations comparing the survivals of patients with different mechanical valves after valve replacement and re-replacement are needed.
The major issue in choosing a valve type is the complications of one valve versus another. With mechanical and bioprosthetic valves, SVD and thrombosis needing re-operation are particularly significant. Also important are major events of thromboembolism and hemorrhage. Therefore, the two valve types were compared with respect to these major valve-specific complications. Other major complications, such as prosthetic valve endocarditis, do not differentiate the two valve types [1, 3, 5]. Mechanical prosthetics implanted at aortic re-replacement were shown to have an insignificantly different freedom from major valve-specific complications than bioprostheses in all age groups. Although statistical significance was not attained, there were strong indications that mechanical valves may be advantageous in patients less than 70 years undergoing aortic valve re-replacement. Similarly, bioprosthetic valves may be shown to be the valve-of-choice in those greater than 70 in a future study with a larger population. After mitral valve re-replacement, almost all analyses significantly favored mechanical valves. A comparative summary of mechanical and bioprosthetic valve performances in patients of different age groups is provided for quick reference to the findings of this study.
Patients less than 60 years receiving a bioprosthetic valve upon mitral valve re-replacement have a high risk of SVD and subsequent reoperation but there was no difference in survival from patients who had mechanical valves. Therefore, if these patients are willing to accept the risk of a third valve operation at 10 years, choosing a bioprosthetic valve may be an option considering the significantly greater freedom from major thromboembolic and hemorrhagic events compared to that of mechanical valves. The risk associated with the inevitable re-reoperation would need to be weighed against the benefits of no anticoagulation. This approach is similar to the conclusion drawn by Spampinato and colleagues [14], where the 20-year cumulative survival of two bioprostheses, even taking into consideration the second operation’s operative mortality, was favorable to the 20-year survival of a single mechanical valve.
The limitations of this study are related to the retrospective nature of the study, even though the database at the University of British Columbia is maintained prospectively. The decision to implant a bioprosthesis or mechanical prosthesis at re-replacement for SVD of a bioprosthesis is determined by the cardiac surgeon, the cardiologist, and the patient with full consideration of valve-related complications and anticipated life expectancy of each patient. The use of antithrombotic therapy is not based on specific protocols and decisions are individualized for each patient.
A further, potential limitation of this study that may have future implications with regard to valve durability is the conception that the current generation porcine and pericardial bioprostheses will likely have extended durability. In this manuscript, 83% of the bioprostheses and 92% of mechanical prostheses implanted at re-replacement were contemporary prostheses. The current, contemporary valves in the United States are inclusive of the Carpentier-Edwards PERIMOUNT (Edwards Lifesciences, Irvine, CA) Hancock II (Medtronic Inc, Minneapolis, MN), Medtronic Mosaic (Medtronic), and the Carpentier-Edwards SAV (Edwards Lifesciences). The following prostheses have been in Canada, many since the early 1980s: CE SAV (Edwards Lifesciences) 1982, Hancock II (Medtronic) 1983, CE-PERIMOUNT 1983 (Edwards Lifesciences), and Medtronic Mosaic (Medtronic) 1994. It is for this reason that we expect the results documented in this manuscript will not change significantly with the current opinion of valve durability with the contemporary valves used in the United States. A number of these valves do now have new sewing cuff configurations to serve as diameter-enhanced aortic bioprostheses and there are two new anticalcification technologies available. The concept that pericardium performs superiorly to porcine with regard to durability is, in our opinion, a fallacy. The recent publication by Jamieson and colleagues [15] shows, essentially, the same durability at 15 years between the CE-SAV aortic and the CE-PERIMOUNT aortic. The nondifferentiation with regard to clinical performance and durability between the CE-SAV aortic and the CE-PERIMOUNT aortic was further amplified in additional recent publications [16, 17]. The CE-SAV is the longest standing contemporary porcine aortic valve on the world market [18]. There is no indication that future results will be different. The contemporary mitral bioprostheses in the United States are the CE-PERIMOUNT, Medtronic Mosaic, and the newly introduced St. Jude Medical BioCor (Epic). In 2005, bioprostheses were implanted in approximately 55% of the Western European market and approximately 80% of the North American market. The authors serve a note of caution that the experience of contemporary valves in the United States is already known with regard to durability from Canadian and Western European countries.
In conclusion, a second bioprosthetic valve was not found to be significantly favorable for aortic or mitral valve re-replacement after SVD of a previous bioprosthetic valve in any age group. However, there was some indication that bioprosthetic valves may be more beneficial than mechanical valves in patients greater than 70 years of age undergoing aortic valve re-replacement. No significant difference was found between mechanical and bioprosthetic valves for patients between 60 and 70 years, while patients less than 60 years with mechanical valves inserted upon aortic valve reoperation enjoyed a significant survival advantage over those with bioprosthetic valves. In the mitral population, mechanical valves were shown to convey a significantly greater freedom from major complications compared with bioprosthetic valves in all age groups.
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Appendix 1
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Appendix 2
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Appendix 3
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References
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- Edmunds Jr LH, Clark RE, Cohn LH, Grunkemeier GL, Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations Ann Thorac Surg 1996;62:932-935.[Abstract/Free Full Text]
- Jamieson WRE, Tyers GF, Janusz MT, et al. Age as a determinant for selection of porcine bioprostheses for cardiac valve replacement: experience with Carpentier-Edwards standard bioprosthesis Can J Cardiol 1991;7:181-188.[Medline]
- Orszulak TA, Schaff HV, Puga FJ, et al. Event status of the Starr-Edwards aortic valve to 20 years: a benchmark for comparison Ann Thorac Surg 1997;63:620-626.[Abstract/Free Full Text]
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Abstract
Introduction
