Ann Thorac Surg 2002;74:S1312-S1317
© 2002 The Society of Thoracic Surgeons
Supplement: Cardiothoracic Techniques and Technologies
The On-X prosthetic heart valve at five years1
Reinhard Moidl, MDa*,
Paul Simon, MDa,
Ernst Wolner, MDa and Members of the On-X Prosthesis Heart Valve Trial
a Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria
* Address reprint requests to Dr Moidl, Department of Cardiothoracic Surgery, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
e-mail: reinhard.moidl{at}akh-wien.ac.at
Presented at the Eighth Annual Cardiothoracic Techniques and Technologies Meeting 2002, Miami Beach, FL, Jan 23–26, 2002.
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Abstract
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BACKGROUND: Multicenter clinical trials were conducted in Europe and North America to evaluate the performance of the On-X bileaflet heart valve prosthesis (Medical Carbon Research Institute, Austin, TX).
METHODS: A total of 532 patients underwent implantation, 303 for aortic valve replacement (AVR) and 229 for mitral valve replacement (MVR), at 20 centers from September 1996 to July 2001. The study followed the guidelines of the AATS/STS. Mean follow-up was 23 months (total 1024 patient-years; maximum 5 years). Poolability analysis was performed to show the equivalence of the populations.
RESULTS: Patients and results were found to be similar and poolable. Freedom from adverse events at 2 years in the study were as follows: thromboembolism, 96.0% for AVR patients and 96.3% for MVR; thrombosis, 100% for AVR and 100% for MVR; bleeding events, 96.6% for AVR and 95.7% for MVR; and overall mortality, 95.2% for AVR and 92.4% for MVR. Median lactate dehydrogenate levels were in the normal range for AVR and MVR patients at all intervals. At 1 year, AVR echocardiographic results for the 19 to 25 valves, respectively, ranged from 1.5 to 2.8 cm2 for effective orifice area and 9.2 to 4.7 mm Hg for mean gradient, and MVR effective orifice area by pressure half-time was 2.8 cm2 and mean gradient was 4.2 mm Hg.
CONCLUSIONS: The two trials have given similarly excellent results for the On-X valve.
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Introduction
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First implanted in September 1996, the On-X Prosthetic Heart Valve (Fig 1)
was designed to optimize bileaflet pyrolytic carbon valve performance. Design features of the valve were intended to address existing deficiencies of mechanical valves, including inadequate hemodynamics in small aortic sizes, occasional incidents of unexplained hemolytic anemia, tissue interference or excessive pannus overgrowth, and (most importantly) thrombotic complications. These design features are pure pyrolytic carbon, inlet flare, natural length-to-diameter ratio, fully opening leaflets, stasis-free hinges, reduced closing contact velocity, full annulus support, and guarding of leaflet motion. The inlet flare, natural length, fully opening leaflets, and maximized use of the annulus while maintaining support all provide for improved hemodynamics. Annulus support and leaflet guarding address tissue interference and pannus overgrowth. The reduced turbulence from improved hemodynamics, pure pyrolytic carbon, reduced closing contact velocity, and smooth backflow patterns through the stasis-free hinges act to reduce hemolysis. All of these features combine to address the reduction of thrombotic complications, with the end goal of a mechanical valve that can tolerate reduced or alternative anticoagulant therapy in low-risk patients. The first 5 years of experience with the valve presented here confirm the success of the design concept.
The multicenter clinical study of the On-X valve was established for the purpose of examining the safety and effectiveness of the valve for eventual market approvals. The study provided data that met all international criteria for determining safety and effectiveness. Clinical outcomes of isolated aortic and mitral valve replacement with the On-X valve were evaluated in terms of mortality, valve-related adverse events, echocardiographic hemodynamics, blood damage, quality of life, and New York Heart Association (NYHA) classification. Early postoperative improvements in echocardiographic hemodynamics were reported earlier by Chambers and colleagues [1] and by Fraund and associates [2].
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Patients and methods
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Patient population and surgery
From September 1996 to July 2001, a total of 532 patients had isolated valve replacement at 11 European and nine North American centers under a standardized protocol. Isolated aortic valve replacement (AVR) occurred in 303 (57%) patients, and isolated mitral valve replacement (MVR) in 229 (43%). In the AVR group, 68.6% of patients were male, whereas in the MVR group, 38% were male. The mean age at implant was 59.6 ± 9.1 years in AVR patients (range 20 to 85 years) and 59.2 ± 10.6 years in MVR (range 21 to 78 years).
Preoperatively, 41.2% of the AVR patients were in NYHA class III, whereas 58.5% of the MVR patients were in class III, indicating that the mitral population was more severely ill to start. In addition, 3.6% of AVR patients had previous cardiac surgery, whereas 28.0% of MVR patients had previous cardiac surgery.
The most common disease etiology was calcific degeneration in AVR patients (48%) and rheumatic heart disease in MVR (37.6%). Other common etiologies were degenerative (24.4% in AVR patients and 27.1% MVR) and endocarditis (2.6% AVR patients and 7.0% in MVR). The valve lesion leading to replacement was 49.3% stenosis, 18.3% regurgitation, and 32.3% mixed in AVR patients, as compared with 12.8% stenosis, 48.9% regurgitation, and 38.3% mixed in MVR. Typical of these populations, 87.0% of AVR patients were in sinus rhythm at surgery, whereas 47.4% of MVR patients were in atrial fibrillation.
Concomitant cardiac surgery was performed in 30.7% of AVR patients and 43.2% of MVR patients. This surgery was predominantly coronary bypass grafting (22.1% of AVR patients and 19.2% of MVR). Implant size distribution was determined for each position. Both distributions were normally distributed over the available sizes, taking into account the combination of sizes allowed by the valve design. Demographic characteristics of the study patients are summarized in Table 1.
Follow-up and data analysis
Follow-up in the study was obtained entirely in clinic or office visits; no telephone or letter follow-up was allowed. Scheduled follow-up occurred at 3 to 6 months postoperatively and at annual postoperative intervals to at least 5 years. At the last report, 15 (2.8%) patients were lost to follow-up and all other patients were being followed actively as of June 1, 2000. In accordance with the protocol, patients were maintained on anticoagulant therapy with target therapeutic international normalized ratio (INR) ranges of 2.5 to 3.5 for AVR patients and 3.0 to 4.5 for MVR unless a contraindication to such therapy arose.
Follow-up was generally available over the first 2 years postoperatively in most patients, with the longest follow-up of 5 years. A total of 426 patients have been followed at 3 to 6 months (312 patients at 1 year, 158 at 2 years, and 124 at 3 years). Total follow-up in the study was 606.0 patient-years for AVR patients and 417.9 patient-years for MVR. The average follow-up for all patients was 23 months. Adverse events were identified and classified in accordance with the AATS/STS [3] guidelines for cardiac valve operations.
Early event rates (
30 days postoperatively) or hospital event rates (before discharge if >30 days) were calculated as simple percentages of patients. Linearized rates are calculated for late events as percent per patient-year of follow-up (or number per 100 years of follow-up). Actuarial analyses took into account both early and late events and were calculated based on the methods of Kaplan and Meier [4].
Echocardiographic data were gathered at discharge and at 1 year, and all data were evaluated by a single cardiologist for consistency. Pressure gradients were calculated using the full Bernoulli equation for AVR patients and the simplified Bernoulli equation for MVR patients. Effective orifice area (EOA) was calculated using the continuity equation in both positions, and the pressure half-time method was also used for MVR patients. EOA was also indexed to body surface area.
Postoperative blood samples for hemolysis were taken at 3 to 6 months and annually, and were compared to preoperative measurements. All samples were shipped to, and analyzed by, a central laboratory.
Quality of life results were determined by analyzing data gathered on the SF-36 Health Survey according to the methods prescribed by the Medical Outcomes Trust, developer of the survey. The NYHA functional classification was evaluated at each follow-up in accordance with the definitions of that society.
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Results
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Mortality
Hospital mortality in the study was 2.44% (13/532) for the whole study, at 1.32% for AVR patients and 3.93% for MVR. One AVR patient died of multiple organ failure 6 weeks postoperatively without discharge from the hospital; thus, the 30-day mortality was 2.26% (0.99% for AVR and 3.93% for MVR). The 12 remaining deaths included 3 MVR patients from sepsis, 5 patients (2 AVR and 3 MVR) from arrhythmias determined by autopsy to be not related to the valve, 1 AVR patient from thromboembolism 10 days postoperatively, 1 MVR patient from ventricular rupture, 1 MVR patient from a perioperative bleed, and 1 MVR patient from cancer. Based on autopsy findings and guidance criteria, only the thromboembolism event classified was believed to be valve related, giving a valve-related early mortality of 0.33% AVR. There were 17 late deaths in the study (8 AVR patients, 1.32%/patient-years; and 9 MVR patients, 2.15%/patient-years). Five sudden deaths (3 AVR patients and 2 MVR) occurred in the study; these are the only deaths that were possibly valve related, although this could not be determined, as autopsy was not performed. Other causes of late deaths include cancer, myocardial infarction, pneumonia, suicide, and congestive heart failure. The actuarial freedom from death at 2 years (Fig 2)
in the study was 95.2% ± 1.4% in AVR patients and 92.4% ± 2.0% in MVR, and the freedom from valve-related or sudden death was 97.4% ± 1.4% in AVR patients and 99.5% ± 0.5% in MVR.
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Fig 2. Event-free curve for overall mortality.Solid linesindicate aortic valve replacement (AVR) patients;broken lines indicate mitral valve replacement (MVR) patients.
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Valve-Related adverse events
Early valve-related adverse events are listed in Table 2
and late valve-related events are given in Table 3.
Early thromboembolic events occurred in 4 AVR patients (1.32%) and 2 MVR patients (0.87%). Late thromboembolic events occurred 15 times, in 8 AVR patients (1.32%/patient-years) and in 7 MVR (1.68%/patient-years). Two events occurred in 1 MVR patient, resulting in a permanent neurologic deficit; all other patients recovered fully from single events. Overall freedom from thromboembolism at 2 years (Fig 3)
was 96.0% ± 1.3% AVR and 96.3% ± 1.4% MVR. There were no thrombosed valves reported in these patients. Early bleeding events occurred three times (0.99%) in AVR patients and 4 times (1.75%) in MVR. Late bleeding events occurred 10 times (1.65%/patient-years) in AVR patients and six times (1.44%/patient-years) in MVR. Late major bleeding events occurred seven times (1.16%/patient-years) in AVR and two times (0.48%/patient-years) in MVR. At 2 years, the actuarial freedom from bleeding was 96.6% ± 1.2% in AVR patients and 95.7% ± 1.5% in MVR (Fig 4).
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Fig 3. Event-free curve for thromboembolism.Solid lines indicate aortic valve replacement (AVR) patients;broken lines indicate mitral valve replacement (MVR) patients.
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Fig 4. Event-free curve for bleeding events.Solid linesindicate aortic valve replacement (AVR) patients;broken lines indicate mitral valve replacement (MVR) patients.
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Prosthetic endocarditis occurred in 5 patients, all late but within the first year postoperatively: 2 AVR patients (0.33%/patient-years) and 3 MVR (0.72%/patient-years). The actuarial freedom from endocarditis at 2 years was 99.2% ± 0.6% AVR and 99.0% ± 0.7% MVR (Fig 5).
All of these patients underwent reoperation for valve replacement and recovered.
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Fig 5. Event-free curve for prosthetic endocarditits. Solid linesindicate aortic valve replacement (AVR) patients; broken lines indicate mitral valve replacement (MVR) patients.
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There were no cases of structural valve failure. Nonstructural valve failure in the form of paravalvular leaks occurred in 13 patients (7 early and 6 late). Two early events were tissue tears in 1 AVR patient (0.33%) and 1 MVR (0.44%), and the remaining early events were minor leaks found on echocardiographic examination and not treated (4 AVR and 1 MVR). In the cases of tissue tears, the patients underwent reoperation, the valves were replaced, and the patients recovered. Three AVR patients (0.50%/patient-years) and 3 MVR patients (0.72%/patient-years) had paravalvular leaks late postoperatively. In 5 cases (3 AVR and 2 MVR), the leaks found on echocardiography were minor in nature, requiring no surgical effort to repair or replace the valves, and the patients’ conditions were being maintained medically. The remaining MVR case was found 4 months postoperatively; this patient underwent reoperation with valve replacement 10 months later and recovered. One MVR patient was reported to have leaflet motion interference, was treated medically, did not undergo reoperation, and recovered. The cause of this event could not be confirmed. The actuarial freedom from paravalvular leak at 2 years was 97.8 ± 0.9 for AVR and 97.2 ± 1.2 for MVR (Fig 6).
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Fig 6. Event-free curve for paravalvular leak.Solid lines indicate aortic valve replacement (AVR) patients;broken lines indicate mitral valve replacement (MVR) patients.
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Total actuarial freedom from valve-related morbidity and mortality (Fig 7)
at 2 years was 88.4% ± 2.1% for AVR and 88.0% ± 2.5% for MVR.
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Fig 7. Event-free curve for total valve-related morbidity and mortality.Solid lines indicate aortic valve replacement (AVR) patients;broken lines indicate mitral valve replacement (MVR) patients.
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Medical outcome
Outcome of valve replacement was determined by examining the preoperative and postoperative NYHA classification of each patient. At 1 year postoperatively, 90.7% of AVR patients and 95.8% of MVR patients were in NYHA class I or II. At the 1-year interval, 73.3% of AVR patients and 88.1% of MVR patients improved one or more classes, 19.1% of AVR patients and 9.3% of MVR patients stayed the same, and 2.3% AVR and 2.5% MVR deteriorated due to adverse events. Quality of life improved statistically in all measures, as shown in Figure 8.
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Fig 8. Quality of life scores based on Short Form–36 (SF-36).Open bars indicate preoperative quality of life score; filled bars indicate quality of life score at 1 year. All changes are statistically significant at p< 0.05.
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As is typical with mechanical heart valves, serum haptoglobin was reduced and serum lactate dehydrogenase was increased postoperatively. The measures of red cells, hematocrit and hemoglobin were all in the midnormal range, and no evidence of hemolytic anemia was found. Results were consistent across all postoperative examinations to 2 years. Importantly, the median serum lactate dehydrogenase level (Table 4),
although increased from preoperative values, was within the normal range for all valve types at each interval, which is atypical for mechanical valves.
Echocardiographic hemodynamics
Echocardiographic hemodynamic data were collected on as many patients as possible, resulting overall in data on 81% of the eligible population at discharge and 94% of the eligible population at 1 year or more of follow-up.
In the aortic position, the mean gradient at discharge ranged from 14 to 7.5 mm Hg and the peak gradient from 27 to 13 mm Hg for valves 19 mm through 27/29 mm, respectively. At the 1-year examination, the corresponding range of mean gradients was 8.5 to 4.8 mm Hg, and of peak gradients was 15.9 to 9.1 mm Hg. The EOA and indexed EOA by size for each examination are shown in Figure 9.
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Fig 9. Effective orifice area (EOA) and indexed effective orifice area (EOAI) for aortic valve. Open bars indicate results at discharge;filled bars indicate results at 1 year.
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For the mitral valve, gradients did not vary statistically by size at either examination, and ranged between 3 and 5 mm Hg for the mean. This result is expected, as all of the mitral valves are based on the same size of housing. Mitral valve EOA and indexed EOA by size and examination, using continuity equation and pressure half-time methods, are shown in Figure 10.
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Fig 10. Effective orifice area (EOA) and indexed effective orifice area (EOAI), by continuity and pressure half-time, for mitral valve.Open bars indicate results at discharge;filled bars indicate results at 1 year.
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Comment
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As with all mechanical valves, a major concern is the long-term need for anticoagulation and the thrombogenic potential associated with these valves. Clinical studies of such valves rightly focus on thromboembolism, thrombosis, and bleeding rates, individually or as a collective index. In this study, patients were maintained on permanent anticoagulant therapy. The sum of the embolic and bleeding events in this study produced a freedom from these events at 2 years of 92.6% ± 1.2% AVR and 92.0% ± 1.4% MVR. Comparable results were reported by Horstkotte and Körfer [5] for both Björk-Shiley and St. Jude Medical valves.
For prosthetic endocarditis in particular, Pomar and Miró [6] noted that the percentage of patients developing this complication in the first 9 months after surgery can be as high as 3%, and that the rate of endocarditis events dropped afterward. Wilson and colleagues [7], in a review of the literature, reported total endocarditis rates between 1% and 3.9%. In this study, the linearized rate for endocarditis was 0.5%/patient-years for AVR and 0.9%/patient-years MVR, consistent with the literature. Gersh and associates [8] noted a time-related decrease in rates for thromboembolic complications after the first year in their center. This time related behavior has occurred in this study as well.
In a review of the literature, Grunkemeier and coworkers [9] report paravalvular leak in mechanical valves ranging from 0% to 2.8%/patient-years in long-term studies. In this study, two early leaks resulted from the friable condition of the patient’s annulus. Two leaks (one early and one late) were minor and did not require intervention. Only one late leak required reoperation. In this experience, the linearized rates for paravalvular leak were 0.50%/patient-years AVR and 0.72%/patient-years MVR, which are within the expected range.
In this experience, the overall survival at 2 years was 95.1% ± 1.5% for AVR and 92.4% ± 2.0% for MVR, and the total freedom from valve-related morbidity and mor-tality was 88.4% ± 2.1% for AVR and 88.0% ± 2.5% for MVR. These rates were similar to the early experience with heart valves reported in many articles, including those by Fiore and colleagues [10] and Burkhardt and associates [11]. In fact, the higher early mortality rate in MVR patients was consistent with the report of Fiore and colleagues, and reflected current practice using mitral repair for the less severe cases of mitral valve disease and replacement for more complicated cases.
The hemodynamic results compare favorably to those reported by Wang and colleagues [12] in a review of the literature. Typically, aortic bileaflet mechanical valves at 19 mm have EOAs of 0.9 to 1.0 cm2, in comparison to this result of 1.56 cm2 at 1 year. In this review, An area of 1.5 cm2 is not consistently reached until valves are size 25 mm.
The On-X valve performs satisfactorily in the first 5-year period in isolated valve replacement. Longer-term follow-up of this patient group is needed to establish the expected rates for late valve-related events as well as the long-term clinical efficacy of the valve. In part because of the improved hemodynamics, the valve is expected to have low thromboembolism rates that appear to justify further study at reduced anticoagulant levels, especially in AVR patients in sinus rhythm.
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Acknowledgments
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The multicenter investigators in the On-X Prosthesis Heart Valve Trial are as follows: Europe: A. Laczkovics, Bochum, Germany; G. Laufer, Vienna, Austria; J. Pomar, Barcelona, Spain; D. Birnbaum, Regensburg, Germany; F. Hehrlein, Giessen, Germany; A. Haverich, Hannover, Germany; F. Mohr, Leipzig, Germany; H. Greve, Krefeld, Germany; H. Oelert, Mainz, Germany; D. Regensburger, Kiel, Germany; and G. Palatianos, Athens, Greece. North America: T. Ivey, Cincinnati, OH; G. Lemole, Newark, DE; S. Szentpetery, Norfolk, VA; J. Metras, Quebec City, PQ; R. Masters, Ottawa, ON; M. Slaughter, Oak Lawn, IL; E. Dilling, Austin, TX; S. Marra, Camden, NJ; and M. Mack, Dallas, TX.
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Footnotes
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1 The members of On-X Prosthesis Heart Valve Trial are listed in the Acknowledgments. 
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References
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- Chambers J., Ely J.L., et al. Early postoperative echocardiographic hemodynamic performance of the On-X Prosthetic Heart Valve: a multicenter study. J Heart Valve Dis 1998;7:569-573.[Medline]
- Fraund S., Pethig K., Wahlers T., et al. On-X bileaflet valve in the aortic position—early experience shows an improved hemodynamic profile. Thorac Cardiovasc Surg 1998;46:293-297.[Medline]
- Edmunds L.H., Clark R.E., Cohn L.H., et al. Guidelines for reporting morbidity, and mortality after cardiac valvular operations. Ann Thorac Surg 1996;62:932-935.[Abstract/Free Full Text]
- Kaplan E.L., Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481.
- Horstkotte D., Körfer R. The influence of prosthetic valve replacement on the natural history of severe acquired heart valve lesions valves. In: DeBakey M.E., ed. Advances in cardiac valves. New York: Yorke Medical Books, 1983:47-86.
- Pomar J.L., Miró J.M. Prosthetic valve endocarditis. In: Piwnica A., Westaby S., eds. Surgery for acquired aortic valve disease. Oxford: ISIS Medical Media, 1997:311-317.
- Wilson W.R., Danielson G.K., Giuliani E.R., Geraci J.E. Prosthetic valve endocarditis. Mayo Clin Proc 1982;57:155-161.[Medline]
- Gersh B.J., Fisher L.D., Schaff H.V., et al. Issues concerning the clinical evaluation of new heart valves. J Thorac Cardiovasc Surg 1986;91:460-466.[Medline]
- Grunkemeier G.L., Starr A., Rahimtoola S.H. Prosthetic heart valve performance: long-term follow-up. Curr Probl Cardiol 1992;17:331-406.
- Fiore A.C., Barner H.B., Swartz M.T., et al. Mitral valve replacement. Randomized trial of the St. Jude and Medtronic Hall Prostheses. Ann Thorac Surg 1998;66:707-713.[Abstract/Free Full Text]
- Burkhardt D., Hoffmann A., Vogt S., et al. Clinical evaluation of the St: a two-year follow-up of 150 patients. J Thorac Cardiovasc Surg 1984;88:432-438.[Abstract]
- Wang Z., Grainger N., Chambers J. Doppler echocardiography in normally functioning replacement heart valves: a literature review. J Heart Valve Dis 1995;4:591-614.[Medline]
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Abstract
Introduction
