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Ann Thorac Surg 2001;71:S273-S277
© 2001 The Society of Thoracic Surgeons

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Bioprosthetic valves and conduits: new developments

Mosaic valve international clinical trial: early performance results

^a University of British Columbia, Vancouver, Canada
^b Albertinen Krankenhaus, Hamburg, Germany
^c Regina General Hospital, Regina, Canada
^d Quebec Cardiology Institute, Quebec, Canada

Address reprints requests to Dr Fradet, 603-575 West 8th Ave, Vancouver, BC, Canada, V5Z 1C6
e-mail: gfradet{at}interchange.ubc.ca

Presented at the VIII International Symposium on Cardiac Bioprostheses, Cancun, Mexico, Nov 3–5, 2000.

	Abstract

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 
Background. A new third generation porcine bioprosthesis was developed in an attempt to improve on hemodynamic performance and durability of current prostheses.

Methods. One thousand, two hundred, sixty patients underwent aortic valve replacement and 366 patients underwent mitral valve replacement between February 1994 and September 2000. The cumulative follow-up was 3,696.3 patient-years for aortic valve replacement and 880.1 patient-years for mitral valve replacement. Follow-up was complete for 95.5% of aortic valve replacement patients and 97.5% of mitral valve replacement patients.

Results. For aortic valve replacement, freedom from valve-related adverse events at 1 year was 96.5% ± 0.5% for antithromboembolic-related hemorrhage and 100% for structural valve deterioration. Freedom from valve-related adverse events at 5 years was 93.8% ± 2.6% for antithromboembolic-related hemorrhage and 99.3% ± 0.9% for structural valve deterioration. For mitral valve replacement, freedom from valve-related adverse events at 1 year was 96.0% ± 1.1% for antithromboembolic-related hemorrhage and 100% for structural valve deterioration. Freedom from valve-related adverse events at 4 years was 92.1% ± 3.7% for antithromboembolic-related hemorrhage and 100% for structural valve deterioration.

Conclusions. These results support the claim that the Mosaic bioprosthetic valve is efficacious and safe, but continued follow-up is mandatory to determine mid- and long-term performance.

	Introduction

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 
The Medtronic Mosaic valve is a third generation stented porcine bioprosthesis built upon the historical durability of the Hancock II valve [1] in an attempt to improve hemodynamic performance and durability. Tissue fixation is with glutaraldehyde and is physiologic, (ie, root-pressure fixation with zero pressure fixation across the leaflets). The tissue is mounted on a flexible polymer stent and treated with alpha amino oleic acid to prevent or delay tissue calcification (antimineralization treatment). The aortic valve has a supraannular configuration and the mitral valve has a generous sewing ring. The mitral valve also comes mounted on a holder allowing retraction of the stents while allowing full visualization of the ring at implant, thus minimizing the possibility of stent-suture entrapment at implantation.

We present the early performance results of a prospective, nonrandomized, multicenter clinical trial. The primary objectives of this study were to evaluate the efficacy, safety, and clinical performance of the Mosaic valve. Seventeen centers participated (see Appendix) and followed a common study protocol. This article provides an assessment of the data available from February 1994 to September 2000.

	Patients and methods

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 
Patients diagnosed with valvular heart disease and requiring isolated replacement of either the aortic or mitral valve were eligible to enter the study. Concomitant procedures (other than valve replacement) were permitted. Patients with active endocarditis at the time of implant were also permitted to enter the study. Patients requiring a concomitant valve replacement or who had a preexisting prosthetic valve in another position were excluded.

A total of 1,626 patients underwent aortic valve replacement (AVR) or mitral valve replacement (MVR). One thousand, two hundred, sixty patients had AVR (801 male, 459 female) with a mean age at implant of 70 years (range, 21 to 89 years) and 366 patients had MVR (172 male, 194 female) with a mean age at implant of 68 years (range, 17 to 84 years). The majority of patients (72.9% of AVR patients and 79.2% of MVR patients) were in New York Heart Association functional class III or IV preoperatively. A total of 13.0% of AVR patients and 23.8% of MVR patients had undergone previous cardiovascular procedures. Concomitant coronary artery bypass procedure was performed in 43.7% of AVR patients and in 42.3% of MVR patients.

Follow-up clinical data and hemodynamic data obtained by echocardiography were required at the early evaluation (before discharge or within 30 days of implant), late evaluation (3 to 6 months postoperative), at 1 year, and annually thereafter. All echocardiographic examinations followed a standard protocol across the investigational sites. Effective orifice area was calculated using the continuity equation. Follow-up was complete for 95.5% of AVR patients and for 97.5% of MVR patients. Cumulative follow-up after AVR was 3696.3 patient-years, with a mean follow-up of 2.9 years per patient (maximum 6.2 years). Cumulative follow-up after MVR was 880.1 patient-years with a mean follow-up of 2.4 years per patient (maximum 6.1 years).

Mortality and valve-related morbidity were classified and reported according to the guidelines of the Society of Thoracic Surgeons and of the American Association of Thoracic Surgery [2]. Early mortality was defined as deaths that occurred within 30 days of implant if the patient was discharged from the hospital, or at any time after implant if the patient was not discharged from the hospital. Early morbid events were those that occurred within the first 30 days of implant. Early event rates were calculated as the number of patients having the event divided by the total number of patients, expressed as a percentage. Late mortality was defined as all deaths that occurred after 30 days postoperative, if the patients were discharged from the hospital. Late morbid events were those events that occurred after 30 postoperative days. Linearized rates (percentage per patient-years) were used to summarize late events and were calculated by dividing the number of late events by the sum of the late patient-years of experience, expressed as a percentage.

Statistical analysis was performed using SAS statistical software. Descriptive statistics were used to summarize the patient population data, operative data, follow-up clinical data, and hemodynamic data. Survival analyses using the Kaplan-Meier method were used to estimate survival and the freedom from valve-related adverse events. Peto’s formula was used for the calculation of the standard errors of these estimates. Events that occurred in the early and late postoperative periods were included in these analyses.

	Results

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 
Aortic valve replacement
The early mortality rate after AVR was 3.3%. Of the 41 early deaths, three were valve-related, 25 were cardiac, 12 were noncardiac, and one was unexplained. The late mortality linearized rate was 3.4% per patient-year. Of the 121 late deaths, 20 were valve-related, 25 were cardiac, 59 were noncardiac, and 17 were unexplained. The causes of valve-related death are summarized in Table 1. One patient died of multiorgan failure 2 days after reoperation for a thrombosed Mosaic aortic valve and replacement of the native mitral valve. One patient died of electromechanical dissociation 4 days after reoperation for structural valve deterioration. Survival at 5 years was 79.5% ± 3.9%. Freedom from valve-related death at 5 years was 97.0% ± 1.8%.

Valve-related adverse event data for AVRs are summarized in Table 2. There were 21 early primary thromboembolic events and two secondary events. At 5 years postoperatively, freedom was 93.4% ± 2.6% from primary thromboembolism, 99.5% ± 0.7% from primary valve thrombosis, 97.4% ± 1.7% from endocarditis, 96.0% ± 2.1% from major antithromboembolic-related hemorrhage, and 99.8% ± 0.5% from major primary paravalvular leak. There were no cases of primary hemolysis reported.

At 1 year postoperatively, 98.4% of AVR patients were in New York Heart Association functional class I or II. In addition, at 1 year, 75.2% of the valves had no regurgitation, 16.0% of the valves had trivial regurgitation, 7.4% of the valves had mild regurgitation, and 1.4% of the valves had moderate or greater regurgitation. Mean gradient and effective orifice area data at 1 year are presented in Table 3.

The antithromboembolic therapy protocol varied among centers. At the time of the early evaluation, 259 patients (73.0%) were on warfarin with or without another agent, an additional 61 patients (17.2%) were on antiplatelet agents, 13 patients (3.7%) were on heparin, and 22 patients (6.2%) were not on any antithromboembolic therapy. At 4 years, out of 85 patients, 37.6% were on warfarin, an additional 43.5% were on antiplatelet agents, and 18.8% were not on any therapy.

Valve-related adverse event data for MVRs are summarized in Table 4. There were 13 early primary thromboembolic events and no secondary events. At 4 years postoperatively, freedom was 92.0% ± 3.8% from primary thromboembolism, 99.2% ± 1.2% from primary valve thrombosis, 96.8% ± 2.4% from endocarditis, 94.3% ± 3.2% from major antithromboembolic-related hemorrhage, and 98.9% ± 1.4% from major primary paravalvular leak. There were no cases of structural valve deterioration, nonstructural valve dysfunction, or primary hemolysis reported. There were no early valve-related reoperations. Freedom from valve-related reoperations at 4 years was 96.7% ± 2.4%. A list of reasons for reoperation is presented in Table 1.

	Comment

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 
From past experience, bioprostheses have been shown to have lower incidence of valve-related adverse events than mechanical prostheses, but at the cost of an increased rate of structural valve deterioration (late valve degeneration) [3], and thus limited longevity. Examination of explanted degenerated porcine bioprostheses has shown the typical mode of failure of these valves to be calcification deposits on the leaflets and tearing near the commissures. Important innovations were incorporated into the design of the Mosaic third generation bioprosthesis, with the hope of improved hemodynamic performance and longevity. These include the zero pressure glutaraldehyde fixation process of the leaflets [4], resulting in a valve with more flexible leaflets through preserved morphology and collagen crimping, and the use of a new biocompatible antimineralization treatment, alpha amino oleic acid, derived from oleic acid, which is a naturally occurring lipid [5]. Like the aortic stentless Medtronic Freestyle, the aortic root is also dilated to a pressure of 40 mm Hg to maximize valve orifice area and decrease the potential for leaflet crowding and suboptimal leaflet motion [6].

One of the primary objectives of this study was to evaluate the safety of the Mosaic bioprosthesis. Postoperative mortality and valve-related morbidity were evaluated to address this objective. The patient population studied was a large, prospective, multicenter, international clinical trial that included 1,626 patients from 17 centers. There was an excellent freedom from thromboembolic events, antithromboembolic-related hemorrhage, and valve thrombosis. The analysis of the data from this study demonstrates the adequate clinical safety performance of this new porcine bioprosthesis up to 5 postoperative years for AVRs and up to 4 postoperative years for MVRs.

The clinical and hemodynamic performance of the Mosaic valve reported in this study is comparable to the early performance of the Hancock II bioprosthetic valve [7], which has now been shown to have very satisfactory clinical results at 12 and 15 years [8, 9]. The Holy Grail of cardiac valvular replacement remains a prosthesis, which would be a nonobstructive, nonthrombogenic tissue valve lasting the patient’s lifetime [10]. It is hoped that this new Mosaic prosthesis will be another step forward toward this ultimate goal. However, continued clinical follow-up is mandatory to characterize the mid- and long-term performance of this new third generation tissue valve, and to demonstrate if the valve will provide increased durability as a result of its design, physiologic fixation process, and anticalcification treatment.

	Footnotes

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 
^* Doctor Paul C. Cartier passed away on January 2, 2001.

	Appendix

 
Mosiac clinical study centers

Institution Investigators Australia Monash Medical Centre, Clayton Jacob Goldstein, MD Prince of Wales Hospital, Randwick Hugh D. Wolfenden, MD Canada Vancouver Hospital and Health Science Centre, St. Paul’s Hospital, Vancouver W. R. Eric Jamieson, MD Regina General Hospital, Regina Edward F. G. Busse, MD Queen Elizabeth II Health Sciences Centre, Halifax John A. Sullivan, MD Hospital Laval, Sainte-Foy Jacques Metras, MD The Toronto Hospital, Toronto Charles M. Peniston, MD Royal University Hospital, Saskatoon Dorothy J. Thomson, MD Foothills Hospital, Calgary Andrew Maitland, MD Atlantic Health Sciences Corporation, St. John Hospital James C. W. Parrot, MD Hamilton Civic Hospitals, Hamilton General Division Irene J. Cybulsky, MD France CHR Cote de Nacre, Caen Dominque Maiza, MD Germany Albertinen Krankenhaus, Hamburg Neils Bleese, MD Stadtliches Krankenhaus Munchen-Bogenhausen Bernhard M. Kemkes, MD New Zealand Green Lane Hospital, Auckland Peter J. Raudkivi, MD Spain Clinico Universitario Valencia, Valencia Eduardo Otero-Coto, MD United Kingdom Glenfield General Hospital, Leicester Andrew W. Sosnowski, MD

	References

Top Footnotes Abstract Introduction Patients and methods Results Comment References

 

1. David T.E., Armstrong S., Sun Z., Kuo J. The Hancock II bioprosthesis at twelve years. Ann Thorac Surg 1998;66:S95-S98.
2. Edmunds L.H., Jr, Clark R.E., Cohn L.H., Grunkemeier G.L., Miller D.C., Weisel R.D. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg 1996;62:932-935.[Abstract/Free Full Text]
3. Fradet G., Jamieson W.R.E., Miyagishima R.T., et al. Performance by age groups in biological and mechanical cardiac valve replacement. Asian Cardiovascular Thoracic Annals 1997;5:130-136.
4. Broom N., Thomsom E.J. Influence of fixation conditions on the performance of glutaraldehyde-treated porcine aortic valves. Thorax 1979;34:166-176.[Abstract/Free Full Text]
5. Gott J.P., Pan-Chih, Dorsey L.M.A., et al. Calcification of porcine valves: a successful new method of antimineralization. Ann Thorac Surg 1992;53:207-216.
6. Lockie K.J., Fisher J., Juster N.P., et al. Biomechanics of glutaraldehyde-treated porcine aortic roots and valves. J Thorac Cardiovasc Surg 1994;108:1037-1042.[Abstract/Free Full Text]
7. David T.E., Armstong S., Sun Z. Clinical and hemodynamic assessment of the Hancock II bioprosthesis. Ann Thorac Surg 1992;54:661-667.[Abstract/Free Full Text]
8. David T.E., Ivanov J., Armstrong S., Feindel C.M., Cohen G. Late results of heart valve replacement with the Hancock II bioprosthesis. J Thorac Cardiovasc Surg 2001;121:268-277.
9. David T.E., Armstong S., Sun Z. The Hancock II bioprosthesis at 12 years. Ann Thorac Surg 1998;66:S95-S98.
10. Schoen F.J., Levy R.J. Tissue heart valves: current challenges and future research perspectives. J Biomed Mater Res 1999;47:439-465.[Medline]

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