Ann Thorac Surg 2001;71:S269-S272
© 2001 The Society of Thoracic Surgeons
Bioprosthetic valves and conduits: new developments
Medtronic mosaic porcine bioprosthesis: midterm investigational trial results
Dorothy J. Thomson, MDa,
W.R. Eric Jamieson, MDb,
Jean G. Dumesnil, MDc,
John J. Burgess, MDd,
Charles M. Peniston, MDe,
Jacques Métras, MDc,
John A. Sullivan, MDf,
James C.W. Parrott, MDg,
Andrew Maitland, MDh,
Irene J. Cybulsky, MDi
a Department of Cardiovascular Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
b University of British Columbia, Vancouver, British Columbia, Canada
c Canadian Clinical Investigators of St.-Foy, Quebec, Canada
d Canadian Clinical Investigators of Regina, Saskatchewan, Canada
e Canadian Clinical Investigators of Toronto, Ontario, Canada
f Canadian Clinical Investigators of Halifax, Nova Scotia, Canada
g Canadian Clinical Investigators of St. John, New Brunswick, Canada
h Canadian Clinical Investigators of Calgary, Alberta, Canada
i Canadian Clinical Investigators of Hamilton, Ontario, Canada
Address reprint requests to Dr Thomson, Division of Cardiovascular Surgery, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, S7N 0W8, Canada
e-mail: djthomson{at}home.com
Presented at the VIII International Symposium on Cardiac Bioprostheses, Cancun, Mexico, Nov 3–5, 2000.
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Abstract
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Background. The midterm clinical and hemodynamic performance of the Medtronic Mosaic porcine bioprosthesis was evaluated in a regulatory trial.
Methods. In nine Canadian centers, 802 bioprostheses (560 aortic and 242 mitral) were implanted between September 1994 and April 1999 in patients with a mean age of 70 years.
Results. Survival for aortic valve replacement at 4 years was 84.4% ± 3.1%. Freedom from valve-related or unexplained death was 95.6% ± 1.9%; structural valve deterioration, 100.0%; reoperation, 96.2% ± 1.7%; major thromboembolism, 96.1% ± 1.8%; and major antithrombotic-related hemorrhage, 96.4% ±1.7%. Echocardiographic derived mean systolic gradient was 13.4 mm Hg at 4 years with an indexed effective orifice area of 0.7 to 0.8 cm2/m2. A significant decrease in left ventricular mass was shown over time in all valve sizes. Survival for mitral valve replacement at 4 years was 79.2% ± 6.8%. Freedom from valve-related or unexplained death was 96.5% ± 3.4%; structural valve deterioration, 100%; reoperation, 97.0% ± 3.2%; major thromboembolism, 95.7% ± 3.8%; and major antithrombotic-related hemorrhage, 95.0% ± 4.2%. Echocardiographically measured averaged mean diastolic gradient was 4.5 mm Hg.
Conclusions. The Medtronic Mosaic bioprosthesis is safe and effective in both the aortic and mitral positions. The valve has low gradients in both positions and excellent left ventricular mass regression in the patients with aortic valve replacement.
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Introduction
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The Medtronic Mosaic valve was designed to incorporate new technology aimed at improving bioprosthetic valve longevity and hemodynamic function. These developments included zero-pressure tissue fixation, alpha amino oleic acid as an antimineralization process, and a low-profile, semiflexible stent [1]. The investigational study of the Medtronic Mosaic porcine bioprosthesis began in Canada in September 1994 and accrual of patients at nine centers continued until March 1998 for aortic valve implants and until April 1999 for mitral valve implants [2]. This prospective, nonrandomized multicenter clinical trial was designed to document morbidity and mortality during follow-up and to assess hemodynamic performance of the valve as measured by echocardiography.
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Patients and methods
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From September 1994 to April 1999, 802 prostheses, 560 (70%) aortic and 242 (30%) mitral, were implanted in 802 patients. There were 513 (64%) men and 289 (36%) women undergoing valve replacement. The mean patient age for aortic valve replacement (AVR) was 70 years (range 21 to 88 years) and for mitral valve replacement (MVR) was 68 years (range 19 to 84 years). Concomitant procedures were performed in 57.7% of AVR; of these 274 (48.9%) were coronary artery bypass grafts (CABG). Concomitant procedures were performed in 61.6% of MVR; of these, 122 (50.4%) were CABG.
The age distribution for AVR patients was: 40 years and less, n = 7 (1.3%); 41 to 50 years, n = 12 (2.1%); 51 to 60 years, n = 31 (5.5%); 61 to 70 years, n = 177 (31.6%); 71 to 80 years, n = 294 (52.5%); and more than 80 years, n = 39 (7%). Preoperatively, 74.6% of patients were New York Heart Association (NYHA) functional class III–IV and 90.2% were in sinus rhythm. Valve size distribution was: 21 mm, 82 patients (14.6%); 23 mm, 220 patients (39.6%); 25 mm, 165 patients (29.5%); 27 mm, 85 patients (15.2%); and 29 mm, 8 patients (1.4%). Cumulative follow-up after AVR was 1,588.8 patient-years; the mean follow-up was 2.9 years (range 0 to 5.3 years). Eight patients (1.4%) were lost to follow-up.
The age distribution for MVR patients was: 40 years and less, n = 6 (2.5%); 41 to 50 years, n = 7 (2.9%); 51 to 60 years, n = 23 (9.5%); 61 to 70 years, n = 76 (31.4%); 71 to 80 years, n = 122 (50.4%); and more than 80 years, n = 8 (3.3%). Preoperatively, 80% of the patients were in NYHA class III–IV and 70.2% were in sinus rhythm. Valve size distribution was 25 mm, 39 patients (16.1%); 27 mm, 85 patients (35.1%); 29 mm, 87 patients (36.0%); 31 mm, 26 patients (10.7%); and 33 mm, 5 patients (2.1%). Cumulative follow-up after MVR was 554.1 patient-years; the mean follow-up was 2.3 years (range 0 to 5.2 years). Four (1.7%) patients were lost to follow-up. Results were presented using STS/AATS guidelines for reporting mortality and valve-related morbidity. Survival and freedom from adverse events at 4 years were reported.
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Results
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Aortic valve replacement
At 1 year, 489 of 494 (99%) AVR patients were in NYHA class I–II; at 4 years, 180 of 188 (95.7%) AVR patients were in NYHA class I–II. Most patients, 73% (range 72.4% to 74.0%), received aspirin and 12% (range 10.9% to 13.7%) received warfarin 1 to 4 years after valve replacement. The early mortality after AVR was 4.5% (25 of 560). Of these early deaths, 16 (64%) patients had undergone concomitant CABG. There were 51 late deaths (3.3%/patient-year) of which 29 (1.9%/patient-year) were noncardiac.
Survival at 4 years was 84.4% ± 3.1%. Freedom from valve-related or unexplained death was 95.6% ± 1.9%. Valve-related complications are detailed in Table 1. Freedom from valve-related complications are illustrated in Figure 1. The 1 patient with a thrombosed valve had a documented coagulation tendency. The time to death for patients with an indexed effective orifice area (EOA) of less than 0.8 cm2/m2 at the early follow-up evaluation was no different (p = 0.7) from the time to death for patients with an indexed EOA of 0.8 cm2/m2 or more. However, the time to death for these patients was significantly different for small versus large valve sizes (p = 0.02). Patients implanted with a 27- or 29-mm valve were more likely to die than patients with a 21-, 23-, or 25-mm valve (risk ratio = 2.0).
Echocardiographic evaluations of AVR prostheses at yearly intervals are illustrated in Figure 2. The average mean gradient was 13.4 mm Hg at 4 years (21 mm, 16.9 mm Hg; 23 mm, 14.5 mm Hg; 25 mm, 11.2 mm Hg; 27 mm, 10.3 mm Hg; 29 mm, 12.0 mm Hg). The average mean EOA was 1.4 cm2 at 4 years and the average indexed EOA was 0.7 cm2/m2 (range 0.7 cm2 for 21 to 23 mm, to 0.8 cm2 for 25 to 29 mm) (Fig 3). There was no difference in survival by valve size or indexed EOA. Figure 4 shows indexed left ventricular (LV) mass regression over time and by valve size. There was a significant decrease in LV mass over time (p < 0.0001). Left ventricular mass was significantly higher for men than for women (p = 0.02). There was also a significant difference in LV mass among valve sizes (p = 0.03); larger valve sizes had larger LV mass. The average LV mass returned to normal at 6 months and remained stable at 2 years. Aortic regurgitation was none, trivial, or mild in 99% (179 of 180) of the patients.
Mitral valve replacement
At 1 year, 197 of 208 (94.7%) MVR patients were in NYHA class I–II; at 4 years, 47 of 50 (94%) MVR patients were in NYHA class I–II. Half of the patients (49.0% to 51.9%) received aspirin and 25% to 38.5% received warfarin 1 to 4 years after valve replacement. Early mortality was 5.4% (13 of 242 patients). Ten (77%) of these patients had undergone concomitant CABG. There were 22 late deaths (4.1%/patient-year).
Survival at 4 years was 79.2% ± 6.8%. Freedom from valve-related or unexplained death was 96.5% ± 3.4%. Freedom from adverse events is shown in Figure 5. Valve-related complications are detailed in Table 1. The patient (71 years at implant) with the thrombosed valve was receiving aspirin at the time of thrombosis. Early postoperatively the patient had atrial fibrillation requiring cardioversion and acquired Staphylococcus epidermidis sepsis. At the 2-year echocardiogram, the mean diastolic gradient was 12 mm Hg and the EOA was 0.49 cm2. At reoperation, more than 3 years after the initial surgical procedure, pannus was found mildly impairing cusp movement at the junction with the leaflets. There was no evidence of calcification or infection.
Echocardiographic evaluation of the MVR prosthesis at yearly intervals was similar, with an average mean diastolic gradient of 4.5 mm Hg (Fig 6) (range 5.3 mm Hg for 25 mm, to 2.8 mm Hg for 31 mm). Average EOA was 1.7 cm2 at 1 and 4 years and across all valve sizes.
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Comment
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The quest for the perfect valve prosthesis continues; issues include valve durability, freedom from adverse events, and good hemodynamic performance. The Mosaic valve is a third-generation bioprosthesis that incorporates aspects of the best current technology based on knowledge and experience gained from past valve generations [2]. Alpha amino oleic acid treatment of the bioprosthesis, aortic predilation, and zero-pressure fixation to preserve collagen crimp and flexibility of the leaflets [1] address durability as much as presently possible for a glutaraldehyde-fixed, stented prosthesis. The efficacy to date is excellent with 100% freedom from structural failure. However, continued observation is indicated in patient groups stratified by age, as most bioprostheses function well for up to 10 years after implant [3, 4].
The Mosaic bioprosthesis also compares well with other second- and third-generation prostheses. No valve-specific problems have yet been identified. Like other stented biological and mechanical valves, the Mosaic is inserted with a single suture line, preferably with a noneverting technique to maximize EOA. It may be implanted in compromised patients who may require concomitant CABG procedures. In the present study 61.5% of patients had concomitant procedures. Patients with a significantly hypertrophied left ventricle and poor coronary artery perfusion remain a challenge for good intraoperative myocardial protection. Many studies continue to document the adverse effect of additional coronary disease and age of early and late outcome [5, 6].
Excellent hemodynamic function of the Mosaic valve has been demonstrated at rest with low mean systolic gradients in the aortic position and diastolic gradients in the mitral position. In the aortic position, LV mass regression has been considered by comparing valve sizes versus LV mass regression over time. In all size groups the average LV mass returned to normal by 6 months and remained so at 2 years. Left ventricular mass regression occurred across all valve sizes, including the 21- to 23-mm sizes, despite identification of mild patient–prosthesis mismatch [7, 8]. Left ventricular mass regression occurred within 6 to 12 months of AVR in most patients with stented and stentless bioprostheses, reflecting resolution of LV hypertrophy associated with the original valve pathology [8–11]. Ideally, valve replacement achieved normal hemodynamics with minimal gradient, smooth nonturbulent flow, and return to normal LV function at rest and exercise. Jin and colleagues [10] studied LV mass regression comparing stented and stentless valves and noted more complete regression in the stentless group. However, systolic hypertension, particularly seen in elderly patients with wide pulse pressures, has also been recognized to affect LV mass regression [5, 9, 10]. This process has also been examined using the concept of patient–prosthesis mismatch first described by Rahimtoola [7] then defined further by Pibarot and coworkers [8]. Mild patient–prosthesis mismatch (indexed EOA 0.6 to 0.8 cm2) was seen in some of our patients with the smaller size valves. Despite mild mismatch there was good LV mass regression, including in patients with smaller size valves. The implications of mild mismatch are still unclear. In this study, no difference in survival was identified in patients with mild mismatch. A nonrandomized case-match study [5] suggested a possible survival advantage for younger patients (aged less than 65 years) with stentless valves. However, there was no advantage in older patients and there were more noncardiac deaths in the stented valve group. Izzat and coworkers [12] looked at two stented valves (St. Jude Medical Bioimplant and Medtronic Intact) and two mechanical valves (St. Jude Medical and CarboMedics) in small sizes. They did not identify a survival disadvantage with patient–prosthesis mismatch. Patients with mismatch should be followed prospectively to further clarify this complex issue.
The Medtronic Mosaic valve continues to provide excellent clinical and hemodynamic performance. Gradients as measured by echocardiography are acceptable up to 4 and 5 years. Although there may be mild patient–prosthesis mismatch in small size aortic valves, no effect on survival was shown and LV mass regression was excellent. Increasing age and concomitant CABG continue to have negative impact on survival in both AVR and MVR.
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Acknowledgments
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We acknowledge the expert assistance of Carolyn Hnatiuk, Verl Sabourin and Florence Chan in preparing the manuscript and figures.
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References
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Abstract
Introduction
