Carpentier-Edwards supra-annular porcine bioprosthesis

J THoRAc CARDIOV ASC SURG 91 :555-565, 1986

Carpentier-Edwards supra-annular porcine bioprosthesis Clinical experience and implantation characteristics The investigational Carpentier-Edwards supra-annular valve was implanted in 592 patients from November, 1981, to February, 1984 (aortic valve replacement in 286, mitral valve replacement in 259, and multiple valve replacement in 47, for a total of 638 prostheses). A previous cardiac operation had been performed in 77 patients (13%). Concomitant procedures were performed in 202 patients (34.1 %), includingcoronary artery bypass in 163 patients. The patient evaluation was 98.6% complete. The early mortality was 7.4% (44 patients) and the late mortality was 6.2% per patient-year (41 patients). The valve-related causes of late mortality were thromboembolism (five), anticoagulant-related hemorrhage (one), and prosthetic valve endocarditis (one). The overall patient survival, including operative death, was 85 % at 2 years. The linearized occurrence rate for valve-related complications was 5.6 % per patient-year (37 events)-thromboembolism 2.7% per patient-year (18), anticoagulant-related hemorrhage 1.2% (eight), prosthetic valve endocarditis 0.8% (five), and periprosthetic leak 0.9% per patient-year (six). There were no cases of primary tissue failure or structural failure. At 2 years, the freedom from valve-related complications was 86.9%, from valve-related mortality, 98.7%, and from valve-related mortality and reoperation, 97.7 %. This valve is fixed in glutaraldehyde at low pressure and is designed to improve durability. It has provided a low incidence of valve-related complications without structural failure. The structural design of the prosthesis does not always conform to the anatomy of bicuspid aortic valves.

W. R. Eric Jamieson, M.D., Alfred N. Gerein, M.D., G. Frank O. Tyers, M.D., Michael T. Janusz, M.D., A. Ian Munro, M.D., Aarne J. Jyrala, M.D., Robert T. Miyagishima, M.D., and Peter Allen, M.D.,

Vancouver, British Columbia, Canada

Glutaraldehyde-preserved biological prostheses have been widely accepted as cardiac valve substitutes. The introduction of glutaraldehyde for the fixation of biological tissue was reported in 1969 by Carpentier and colleagues.I The first-generation biological prostheses were introduced between 1970 and 1975. The Hancock porcine bioprosthesis was available in the early 1970s and the Ionescu-Shiley pericardial valve and the Carpentier-Edwards porcine valve in 1975. Biological prostheses have been shown to provide a low incidence of From the University of British Columbia, Vancouver, British Columbia, Canada. Read at the Eleventh Annual Meeting of The Western Thoracic Surgical Association, Incline Village, Ncv., June 16-20, 1985. Address for reprints: Dr. W. R. Eric Jamieson, Division of Cardiovascular and Thoracic Surgery, Department of Surgery, U.B.C., 910 West 10th Ave., Vancouver. s.c.. Canada V5Z 4E3.

valve-related complications, especially thromboembolism,2 but the durability and hemodynamic performance of certain biological valves have caused surgeons and cardiologists considerable concern. Degeneration of both porcine and pericardial valves has been shown to be time related." The failure mode is that of calcification, tears, and perforations. The incidence of degeneration because of calcification in children and adolescents is 40% to 50% at 4 years, whereas degeneration in the adult population is approximately 20% at 10 years." 14 The hemodynamic performance of the porcine bioprostheses has been inferior to that of the pericardial prostheses, especially in the smaller sizes.":" The deficiencies of biological valves stimulated extensive investigation to provide improvements. In 1982 Carpentier and colleagues" introduced the CarpentierEdwards supra-annular porcine bioprosthesis in an attempt to improve transvalvular gradients and reduce ol2

555

556

The Journal of Thoracic and Cardiovascular Surgery

Jamieson et al.

Table I. Number of patients and valves

Table

Operation

Total patients

Total valves

AVR MVR MR

286 259 47

286 260 92

Total

592

638

Table II. Operative and early* deaths Operation

No. of operations

AVR MVR MR

286 260 47

15 26 3

Totals

593

44

I

Low output syndrome/congestive heart failure Myocardial infarction/arrhythmia Technical error Noncardiac .cause Sepsis Cerebrovascular accident Infective endocarditis

19

Total

44*

12 5 5 I I I

*AVR, 15; MVR, 26; MR, 3.

Deaths

No.

m. Causes of early postoperative deaths

%

5.2 10.0 6.4 7.4

*Less than 30 days.

fatigue lesions and calcifications. The teaching hospitals of the University of British Columbia commenced investigation of this prosthesis in 1981 and 1982 following the regulations of the Food and Drug Administration of the United States. This paper documents our initial and continued experience with this second-generation bioprosthesis. The prosthesis was designed for implantation in the supra-annular position rather than within the anulus to provide an orifice diameter of the same dimensions as the patient's anulus diameter. The valve was designed to optimize the flexibility of the Elgiloy wire stent and the porcine tissue was fixed in glutaraldehyde at low pressure (4 mm Hg). The mitral prosthesis was designed with a reduction of the stent height to reduce protrusion into the ventricular cavity. The manufacturer reported improved in vitro durability and hemodynamics.

Metbods The methods for assessing cardiac valvular prostheses used at the University of British Columbia have been previously reported and were designed for comprehensive comparison of all valve-related complications. 10 The valve-related complications are thromboembolism, anticoagulant-related hemorrhage, prosthetic valve endocarditis, periprosthetic leak, and prosthesis failure. Reoperations or deaths resulting from any of these complications are considered to be valve-related reoperations or deaths. Reoperation for repair or replacement of another native valve or other cardiac abnormalities unrelated to the prosthesis (e.g., coronary artery disease) is not included. The assessment allows for separation of valve survival from patient survival. The multiple deere-

Table IV. Causes of late postoperative deaths Congestive heart failure Acute myocardial infarction/arrhythmia Cardiac tcmponade/ anticoagulant-related hemorrhage Thromboembolism/cerebrovascular accident Prosthetic valve endocarditis Aortic aneurysm Other

9 9 5

2 I II

Total

41*

4

*;\VR, 15; MVR, 19; MR, 7.

ment analysis technique for assessing valve survival of various types of prostheses over time was detailed in 1982 by Bodnar, Wain, and Haberman.'? The definitions of the valve-related complications are as follows: Thromboembolism is defined as all new focal neurologic deficits, either transient or permanent, or peripheral emboli diagnosed at embolectomy. Cerebrovascular accidents occurring intraoperatively are not considered to be valve-related thromboembolism. Anticoagulant-related hemorrhage includes internal or external bleeding that necessitates hospital care, including transfusion, or extensive outpatient care. Prosthetic valve endocarditis is defined as any documented infection of the prosthesis. Operative management of prosthetic valve endocarditis is determined by the presence of progressive and severe congestive heart failure, systemic emboli, or persistent sepsis. Periprosthetic leak includes all episodes of periprosthetic leak documented by cardiac catheterization, reoperation, or autopsy. This category excludes those patients having a periprosthetic leak caused by infective endocarditis, in which case the complication is listed as prosthetic valve endocarditis. Prosthesis failure is defined as any structural failure of the prosthesis causing stenosis or insufficiency, including leaflet disruption, calcification, stent failure,

Volume 91

Carpentier-Edwards supra-annular porcine valve

Number 4 April, 1986

557

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0

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Fig. 1. Patient survival.

or thrombosis, disclosed by cardiac catheterization, reoperation, or autopsy. This category excludes valve failures resulting from infective endocarditis or periprosthetic leak, which are listed separately. The valve-related complications are expressed as linearized occurrence rates or freedom from valverelated complications expressed actuarially. The definitions of the freedom from valve-related complications are as follows: Freedom from all valve-related complications is the actuarial proportion of patients who remain free from any valve-related complications, including those causing death or reoperation. Freedom from mortality due to valve-related complications denotes the actuarial proportion of patients who are alive or have died of a non-valve-related cause. Freedom from valve-related mortality or reoperation denotes the actuarial proportion of patients who remain free from valve-related death or from reoperation for a valve-related cause.

Patients The teaching hospitals of the University of British Columbia have used primarily porcine bioprostheses for valvular substitutes since 1975. To date approximately 2,400 patients have received porcine bioprostheses. The use of the Hancock porcine valve and the CarpentierEdwards standard porcine prosthesis was commenced in 1975 and terminated in late 1981 in favor of the Carpentier-Edwards supra-annular porcine bioprosthesis fixed in glutaraldehyde at low pressure. This prosthesis is continually being used at our hospitals. Between November, 1981, and February, 1984, a total of 638 Carpentier-Edwards supra-annular porcine

bioprostheses were implanted in 592 patients-aortic valve replacement (AVR) 286, mitral valve replacement (MVR) 259, and multiple valve replacement (MR) 47 (Table I). Previous cardiac operations had been performed in 77 patients (13%). Concomitant procedures were performed in 202 patients (34.1%), including coronary artery bypass in 163. The cumulative follow-up for all patients was 662 patient-years (AVR 331 patient-years, MVR 283 patient-years, and MR 48 patient-years). The patient evaluation was 98.6% complete.

Results The early mortality was 7.4% (44 patients) (Table II). The mortality for AVR was 5.2% (15 patients), MVR 10.0% (26 patients), and MR 6.4% (three patients). The causes of the early mortality are shown in Table III. Cardiac-related causes contributed to 70% (31 patients) of the deaths. There were 41 late deaths in the series at the time of evaluation in September, 1984. The late mortality, expressed as a linearized occurrence rate, was 6.2% per patient year, overall. The causes of late deaths are shown in Table IV. The valve-related causes of late mortality were thromboembolism (five), anticoagulant-related hemorrhage (one), and prosthetic valve endocarditis (one). There were no deaths related to periprosthetic leak, prosthesis failure, or reoperation. The overall patient survival rate including operative deaths, expressed by the life-table method, was 85.0% ± 2.3% at 2 years (Fig. 1). The survival rate for AVR patients was 88.6% ± 3.2% at 2 years; for MVR patients, 82.3% ± 3.3%; and for MR patients, 78.3% ± 10.4%.

558

The Journal of Thoracic and Cardiovascular Surgery

Jamieson et al.

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(;AIl valves

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Table V. Valve-related complications (linearized morbidity and mortality rates and events)* Type of valve replacement Morbidity-mortality Thromboembolism Overall incidence Deaths Anticoagulant-related hemorrhage Overall incidence Deaths Prosthetic valve endocarditis Overall incidence Deaths Periprosthetic leak Overall incidence Deaths Reoperation Overall incidence Deaths

I

MR

Overall

9 (3.2) 3 (1.1)

3 (6.2)

\8 (2.7) 5 (0.8)

7 (2.1) I (0.4)

1 (2.1)

8 (1.2) \ (0.2)

I (0.3)

2 (0.7)

2 (4.1) 1 (2.1)

5 (0.8) 1 (0.2)

2 (0.6)

4 (1.4)

6 (0.9)

3 (1.1)

3 (0.5)

AVR 6 (1.8) 2 (0.6)

MVR

I

Legend: There were no instances of primary tissue failure.

"Figures in parentheses indicate percent per patient-year or episodes per 100 patient-years.

The linearized occurrence rate for valve-related complications was 5.6% per patient-year (37 events) and the fatality rate was 1.1% per patient-year (seven events). The freedom from valve-related complications was 86.9% ± 5.4% at 2 years (Fig. 2). The linearized occurrence rates and number of events for all valve-related complications are shown in Table V. The overall rates were as follows: for thromboembolism, 2.7% per patient-year (18 cases), for anticoagulantrelated hemorrhage, 1.2% per patient-year (eight cases), for prosthetic valve endocarditis, 0.8% per patient-year (five cases), and for periprosthetic leak, 0.9% per patient-year (six cases). There were no cases of prosthesis failure (primary tissue failure or structural failure). Reoperation for valve-related complications was necessary in three patients who had had MVR. Reoperation

was performed in two patients for periprosthetic leak and one patient for prosthetic valve endocarditis. At reoperation the periprosthetic leaks were repaired and the prosthesis involvedwith endocarditis was successfully replaced. The freedom from valve-related complications, reoperation, and death is shown in Figs. 2 to 5. The freedom from all valve-related complications was 86.9% ± 5.4% at 2 years (AYR, 93.3% ± 6.0%; MYR, 86.7% ± 6.4%). The freedom from valve-related mortality was 98.7% ± 1.0% (AYR, 99.6% ± 0.8%; (MYR, 98.2% ± 1.8%; MR, 97.1% ± 3.9%). The freedom from valve-related mortality and reoperation was 97.7% ± 1.2% (AYR, 99.5% ± 0.8%; MYR, 96.4% ± 2.6%; MR, 97.1% ± 3.9%). The preoperative and postoperative New York Heart

Volume 91 Number 4

Carpentier-Edwards supra-annular porcine valve 5 5 9

April, 1986

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15

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Fig. 4. Freedom from valve-related death and reoperation.

Association (NYHA) functional classification is shown in Fig. 6. Preoperatively, 92.6% were in either NYHA Class III or IV, whereas postoperatively 95.7% were in NYHA Class I or II. Major and minor thromboembolic events are delineated in Table VI. The freedom from major thromboembolic events was 1.7% per patient-year (11 events) and for minor events, 1.1% per patient year (seven events). The freedom from thromboembolism, the most significant valve-related complication, was 91.3% ± 4.8% at 24 months (Fig. 5).

Implantation characteristics The implantation characteristics of the prosthesis are satisfactory. The investigators have had no concern with the mitral prosthesis. The structural design.of the aortic prosthesis and the annular anatomy must be given full consideration by the implanting surgeon. The highly scalloped sewing ring may not conform appropriately in some cases of bicuspid anuli, especially in the true bicuspid anulus without a rudimentary commissure.

This concern became evident when hemodynamically insignificant regurgitant murmurs that could not be attributed to a periprosthetic leak were noted in at least seven patients. It is believed that the shape of the flexible stent was altered slightly and that this contributed to incomplete coapatation of the leaflets and slight regurgitation. These patients are under surveillance and hemodynamic left ventricular compromise has not been noted. Discussion The glutaraldehyde-preserved biological prostheses, both porcine and pericardial, have received wide acceptance as cardiac valve substitutes. These tissue prostheses have provided a very satisfactory quality of life for patients requiring valvular replacement. 3,5,8. I 1,17 The bioprostheses have afforded a low incidence of valverelated complications, especially thromboembolism. In our experience the incidence of thromboembolism has been consistently less than 2% per patient-year." II, 12 There have been two major concerns with biological

The Journal of

560 Jamieson et al.

Thoracic and Cardiovascular Surgery

92 272

234

{SF o 1

263 226 566

261 218 552

202 173 430

166 143 356

131 115 277

96 85 208

71 56 152

23 18 45

3

6

9

12

15

18

21

27

I

I

I

I

I

I

I

I

30

Months

Fig. 5. Freedom from thromboembolism.

valves, namely, hemodynamics, especially in small porcine bioprostheses, and long-term durability of both the porcine and pericardial prostheses. The smaller porcine prostheses have obstructive properties, especially in the aortic position.4. 15, 16. 20 The concern over durability of biological valves stems from long-term development of leaflet failure and calcification.v': 21,22 The concern over inferior hemodynamics and durability of standard bioprostheses has led manufacturers to modify design and tissue preservation techniques. The Carpentier-Edwards supra-annular valve and the Hancock II prosthesis have been developed in an attempt to meet these concerns. 18.23 The importance of the flexible stent was first documented by Reis and associates" and the importance of low-pressure fixation with glutaraldehyde by Broom." Broom demonstrated that compressive flexure induced structural damage because the valve opened with a localized hinge mechanism and not with a smooth rolling action. Carpentier and colleagues," in 1982, introduced the supra-annular valve in an attempt to reduce transvalvular gradients and fatigue lesions. This prosthesis is designed for implantation in the supra-annular position and uses the spaces of the coronary sinuses to provide a prosthesis orifice diameter similar to the patient's valve anulus. The valve tissue is fixed with glutaraldehyde at 4 mm Hg to maintain the normal configuration of the collagen and elastic fibers to avoid fatigue-induced injury. The inanufacturer of the Hancock II porcine bioprosthesis has incorporated changes in the prosthesis to accomplish these aims." This prosthesis has a larger effective orifice area and a Delrin support rather than the polypropylene support used previously. The Delrin support is designed to reduce fatigue stress and prevent creep properties, which were observed with the first-generation Hancock prosthesis. Our experience has been with the CarpentierEdwards supra-annular porcine bioprosthesis, an experi-

ence showing an overall low incidence of valve-related complications including the lack of primary tissue failure in the early follow-up period. These new-generation prostheses have preliminary calcification mitigation treatment. 26 The pathogenesis of primary tissue degeneration has received extensive consideration. Spray and Roberts" maintained that glutaraldehyde-treated tissue is not biologically inert. The changes found in glutaraldehyde-fixed tissue are somewhat similar to those observed in formalin-fixed heterograft tissue. The pathologic changes that occur after implantation have been described by Ferraris," Ishihara," and their associates. The proteoglycan components of the spongiosa are lost and the delamination and separation leaves empty spaces in the spongiosa that are filled by blood elements that initiate calcification. There is also progressive disruption of collagen, erosion of the vascular endothelial surfaces, aggregation of platelets, and accumulation of lipids. The calcification initiated in the spongiosa, designated as internal calcification, may lead to perforations and tears. These perforations and tears have been classified by Ishihara and colleagues.22, 29 The collagen breakdown (caused by reversal of glutaraldehyde cross-linking and hydrolysis of collagen), mechanical stress forces, and internal and later external calcium formation lead to degeneration. The calcium occurring at the commissures initiates the leaflet

tears.v" Calcification of biological valves in children has been a major problem."> The calcium mitigation action of surfactant is not fully known, but Carpentier and associates" believe that the hydrophilic part of surfactant inhibits lipid and phospholipid penetration of tissues, which is a preliminary process in calcification. Carpentier and co-workers" have further extended calcium mitigation evaluation beyond that incorported in the supra-annular prosthesis. These investigators are

Volume 91 Number 4 April, 1986

Carpentier-Edwards supra-annular porcine valve

Table VI. Thromboembolism (major and minor events)*

Events Opera/ion

Total

Major

AVR MVR MR

286 260

3 (0.9) 6 (2.1)

47

Total

592

2 (4.1) 11 (1.6)

I

56 1

%

100

80 Minor

Deaths

3 (0.9) 3 (1.1) 1 (2.1) 7(1.1)

2 (0.6)

60

3 (1.1)

40

5 (0.8)

'Figures in parentheses indicate percent per patient-year or episodes per 100 patient-years.

evaluating the rate ofcalcification reduction by decreasing tissue phosphate content by blocking calcium binding sites with magnesium chloride, HEPES buffer, and various surfactants. The Carpentier-Edwards supra-annular valve has shown a low rate of valve-related complications, as have the first-generation porcine bioprostheses." tl,36,37 There were no cases of primary tissue failure during the evaluation period or since, in our ongoing experience. The high rate of thromboembolism, 2.7% per patientyear, compared to our overall porcine valve experience of less that 1.5% per patient-year, probably reflects the early stage of evaluation. The linearized rate of thromboembolism tends to fall with time. 8. 12 Use of anticoagulation for the same previously documented indications has caused an anticoagulant-related hemorrhage rate of 1.2% per patient-year. The occurrence of prosthetic valve endocarditis remains at less that 1% per patientyear. The clinical experience with biological prostheses is approaching 15 years. Gallucci and colleagues" have the longest documented experience with the Hancock prosthesis. In 1984 they reported that the freedom from primary tissue failure at 13 years was 58%. At the 11 year evaluation period these investigators reported freedom from primary tissue failure of 74% in the mitral position and 66% in the aortic position.' The mode of failure was stenosis caused by calcific deposition and cusp stiffening and incompetence caused by commissural detachment at the site of calcium infiltration. Magilligan and co-workers" also have shown that degeneration is time related-80% at 9 years and 69% at 10 years. The degeneration of tissue valves has been even more progressivein children.v" Carpentier and others" have reported calcification leading to reoperation or death in approximately 50% of children by 5 years. The degenerative process is greater on the left side of the heart, probably because of an accelerated rate of mechanical damage from higher pressures in systole." The pericardial valve has fared less well than the porcine

20

o

L..-

- - '_ _

IIPre-Op"'

IV

II III Post-Op

IV

Fig. 6. Preoperative and postoperative New York Heart Association classifications.

bioprostheses.":" The Ionescu-Shiley pericardial valve is the only long-term pericardial substitute." The primary failure mode of the first-generation pericardial valve, that is, tears along the free edge of the leaflets near the stent posts, seems to be a structural problem with altered mechanical stress.39, 40 Gabbay and colleagues'? have reported that degenerative findings are similar in vivo and in vitro. These authors believe that failure in the mitral position may occur suddenly. The new-generation biological valves have been found to have superior hemodynamic characteristics." The hemodynamics of the first-generation biological valve are well documented by Chairman," Lee," and Rothkopf," The Carpentier-Edwards valve was slightly superior to the Hancock valve but similar to the Hancock modified-orifice prosthesis. The Ionescu-Shiley pericardial valve has better hemodynamic properties than porcine prostheses. Cosgrove and associates," in a well-documented intraoperative study, found that the Carpentier-Edwards supra-annular valve is superior to the standard porcine valve but the Carpentier-Edwards pericardial valve is superior to both. Walker and colleaguesv" have assessed transvalvular energy loss with both previous and new-generation biological valves. The differences do not appear to be clinically significant. The first report on calcium mitigation studies was presented by Arbustini and colleagues" in 1984. The surfactant-treated porcine and pericardial prostheses were evaluated in a sheep model of tricuspid valve replacement. The chemical process decreased calcification in the porcine valve but not in the pericardial valve. In the rat model, with the valves implanted subcutaneously, these processeswere effective for both porcine and pericardial tissue, but in the bloodstream the treated porcine tissue was superior.

5 6 2 Jamieson et af.

In evaluating the continued use of bioprostheses, several factors must be considered, particularly the overall freedom from valve-related complications and the potential for catastrophic sudden failure. Review of several comparison series of mechanical and biological prostheses affords us some information on which to base this decision.3, 46. 47 The freedom from all valve-related complications favors biological valves, at least until altered durability becomes manifest. The majority of authors report that sudden catastrophic failure is not observed with biological prostheses.6, 47, 48 This lack of catastrophic failure affords the opportunity for an elective safe reoperation. Gallo and colleagues" reported that the time from initial diagnosis of degeneration to reoperation was 5 months for the aortic prosthesis and 11 months for the mitral prosthesis. Pomar and associates/ agreed that mechanical failure is sudden and dramatic, but approximately 40% of bioprosthetic failures necessitate urgent reoperation. Conclusion This prospective study of the Carpentier-Edwards supra-annular valve was undertaken to assess the influence of improved fixation and preservation techniques on long-term durability. Our general satisfaction with the prosthesis has prompted its continued use. The problem of placing the scalloped sewing ring with the flexible support structure in an anatomic location, such as the true bicuspid aortic anulus, appears to be real and the implanting surgeon must take this into consideration. The prosthesis has afforded our patients a low rate of valve-related complications and a negligible risk of mortality related to valve-related complications. The influence of low-pressure fixation with glutaraldehyde and the commencement of calcification mitigation techniques will require continued long-term assessment of this series and others. There have been no structural or primary tissue failures at this stage of evaluation. We anticipate that the Carpentier-Edwards supra-annular valve will afford our patients an excellent quality of life with extended prosthesis durability. Appreciation is extended to our research assistants, Ms. Joan MacNab and Ms. Florence Chan, for their work. We appreciate the support of our surgical colleagues at the Vancouver General Hospital and St. Paul's Hospital at the University of British Columbia. We thank Ms. Gayle Whtoff and Ms. Vicki Chor for preparing the manuscript. REFERENCES Carpentier A, Lemaigre G, Robert L, Carpentier S, Dubost C: Biological factors affecting long-term results of valvular heterografts. J THORAC CARDIOVASC SURG 58:467-481, 1969

The Journal of Thoracic and Cardiovascular Surgery

2 Pomar JL, Bosch X, Chaitman BR, Pelletier C, Grondin CM: Late tears in leaflets of porcine bioprostheses in adults. Ann Thorac Surg 37:78-83, 1984 3 Cohn LH, Allred EN, DiSesa VJ, Sawtelle K, Shemin RJ, Collins JJ Jr: Early and late risk of aortic valve replacement. A 12 year concomitant comparison of the porcine bioprosthetic and tilting disc prosthetic aortic valves. J THORAC CARDIOVASC SURG 88:695-705, 1984 4 Pelletier C, Chaitman BR, Baillot R, Val PG, Bonan R, Dyrda I: Clinical and hemodynamic results with Carpentier-Edwards porcine bioprosthesis. Ann Thorac Surg 34:612-624, 1982 5 Gallucci V, Bortolotti U, Milano A, Valfre C, Mazzucco A, Theine G: Isolated mitral valve replacement with the Hancock bioprosthesis. A 13-year appraisal, Ann Thorac Surg 38:571-578, 1984 6 Gallucci V, Valfre C, Mazzucco A, Bortolotti U, Milano A, Chioin R, Dalla Volta S, Cevese PG: Heart valve replacement with the Hancock bioprosthesis. A 5-11 year follow-up, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 9-24 7 Hetzer R, Topalidis T, Borst HG: Thromboembolism and anticoagulation after isolated mitral valve replacement with porcine heterografts, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books,pp 172-183 8 Jamieson WRE, Janusz MT, Miyagishima RT, Munro AI, Tutassura H, Gerein AN, Burr LH, Allen P: Embolic complications of porcine heterograft cardiac valves. J THORAC CARDIOVASC SURG 81:626-631, 1981 9 Jamieson WRE, Janusz MT, Tyers GFO, Allen P, Munro AI, Burr LH, Gerein HN, Ling H, Miyagishima RT, Tutassura H: Early durability of the Carpentier-Edwards porcine bioprosthesis, Concepts and Controversies in Cardiovascular Surgery, MJ Kaplitt, 18 Borman, eds. Chap 12, New York, 1983, Appleton-Century-Crofts, pp. 111133 10 Jamieson WRE, Pelletier LC, Janusz MT, Chaitman BR, Tyers GFO, Miyagishima RT: Five-year evaluation of the Carpentier-Edwards porcine bioprosthesis. J THORAC CARDIOVASC SURG 88:234-333, 1984 II Janusz MT, Jamieson WRE, Allen P, Munro AI, Miyagishima RT, Tutassura H, Burr LH, Gerein AN, Tyers G FO: Experience of the Carpentier-Edwards porcine valve prosthesis in 700 patients. Ann Thorac Surg 34:625-633, 1982 12 Jamieson WRE: Tissue valves for cardiac valve replacement. Can J Surg 28:499-505, 1985 13 Carpentier A, Nashref A, Carpentier S, Goussef N, Reiland J, Levy RJ, Fishbein MC, El Asmar B, Benomar M, EI Sayed S, Donzeau-Gouge PG: Prevention of tissue valve calcification by chemical techniques, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 320-327

Volume 91 Number 4 April, 1986

14 Magilligan DJ Jr, Lewis JW Jr, Tilley B: The porcine bioprosthetic valve. Twelve years later. J THORAC CARDIO. VASC SURG 89:499-507, 1985 15 Chaitman BR, Bonan R, Lepage G, Tubau JF, David PR, Dyrda I Grondin CM: Hemodynamic evaluation of the Carpentier-Edwards porcine xenograft. Circulation 60:1170-1182, 1979 16 RothkopfM, Davidson T, Lipscomb K, Narahara K, Hillis LD, Willerson JT, Estrera A, Platt M, Mills L: Hemodynamic evaluation of the Carpentier-Edwards bioprosthesis in the aortic position. Am J CardioI44:209-214, 1979 17 lonescu MI, Smith DR, Hasan SS, Chidambaram M, Tandon AP: Clinical durability of the pericardiaI xenograft valve. Ten years' experience with mitral replacement. Ann Thorac Surg 34:265-277, 1982 18 Carpentier A, Dubost C, Lane E, Nasef A, Carpentier S, Reiland J, Deloche A, Fabiani J-N, Chauvaud S, Perier P, Maxwell S: Continuing improvements in valvular prostheses. J THORAC CARDIOVASC SURG 83:27-42,1982 19 Bodnar E, Wain WH, Haberman S: Assessment and comparison of the performance of cardiac valves. Ann Thorac Surg 34: 146-156, 1982 20 Lee G, Grehl TM, Joye JA, Kaku RF, Harter W, DeMaria AN, Mason DT: Hemodynamic assessment of the new aortic Carpentier-Edwards bioprosthesis. Cathet Cardiovasc Diagn 4:373-381, 1978 21 Bolooki H, Mallon S, Kaiser GA, Thurer RJ, Kieval J: Failure of Hancock xenograft valve. Importance of valve position (4- to 9-year follow-up). Ann Thorac Surg 36:246-252, 1983 22 Ishihara T, Ferrans VJ, Boyce SW, Jones M, Roberts We: Structure and classification of cuspal tears and perforations in porcine bioprosthetic cardiac valves implanted in patients, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 362-377 23 Wright JTM, Eberhardt CE, Gibbs ML, Saul T, Gilpin CB: Hancock II-an improved bioprosthesis, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 425-444 24 Reis RL, Hancock WD, Yarbrough JW, Glancy D, Morrow AG: The flexible stent. A new concept in the fabrication of tissue heart valve prostheses. J THORAC CARDIOVASC SURG 62:683-689, 1971 25 Broom ND: Fatigue-induced damage in glutaraldehydepreserved heart valve tissue. J THORAC CARDIOVASC SURG 76:202-211,1978 26 Carpentier A, Nashef A, Carpentier S, Ahmed A, Goussef N: Techniques for prevention of calcification of valvular bioprostheses. Circulation 70:Suppl I: 165-168, 1984 27 Spray TL, Roberts WC: Structural changes in porcine xenografts used as substitute cardiac valves. Gross and histologic observations in 51 glutaraldehyde-preserved Hancock valves in 41 patients. Am J CardioI40:319-330, 1977

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28 Ferrans VJ, Spray TL, Billingham ME, Roberts We: Structural changes in glutaraldehyde-treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron microscopic observations in 12 patients. Am J Cardiol 41:1591-1183, 1978 29 Ishihara T, Ferrans VJ, Boyce SW, Jones M, Roberts We: Structure and classificatiorl of cuspal tears and perforations in porcine bioprosthetic cardiac valves implanted in patients. Am J Cardiol 48:665-678, 1981 30 Milano A, Bortolotti U, Talenti E, Valfre C, Arbustini E, Valente, M, Mazzucco A, Gallucci V, Thiene G: Calcific degeneration as the main cause of porcine bioprosthetic valve failure. Am J Cardiol 53: I066-1070, 1984 31 Oyer PE, Miller DC, Stinson EB, Reitz BA, MorenoCabral RJ, Shumway NE: Clinical durability of the Hancock porcine bioprosthetic valve. J THORAC CARDlO· VASC SURG 80:824-833, 1980 32 Geha AS, Hammond GL, Laks H, Stansel HC, Glenn WWL: Factors affecting performance and thromboembolism after porcine xenograft cardiac valve replacement. J THORAC CARDIOVASC SURG 83:377-384, 1982 33 Oyer PE, Stinson EB, Miller DC, Jamieson SW, Reitz BA, Baumgartner W, Shumway NE: Clinical analysis of the Hancock porcine bioprosthesis, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 539-551 34 Odell JA: Calcification of porcine bioprostheses in children, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 231-237 35 Villani M, Bianchi T, Vanini V, Tiraboschi R, Crupi GC, Pezzica E, Parenzan L: Bioprosthetic valve replacement in children, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 248-255 36 Magilligan DJ Jr, Lewis JW Jr, Jara FM, Lee MW, Alam M, Riddle JM, Stein PD: Spontaneous degeneration of porcine bioprosthetic valves. Ann Thorac Surg 30:259266, 1980 37 Magilligan DJ Jr, Lewis JW Jr, Stein PD, Lakier J, Smith DR: Decreasing incidence of porcine bioprosthetic degeneration, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 559-567 38 Brais MP, Bedard JP, Goldstein W, Koshal A, Keon WJ: lonescu-Shiley pericardial xenografts. Follow-up up to 6 years. Ann Thorac Surg 39: I05-111, 1985 39 Gabbay S, Bortolotti U, Wasserman F, Factor S, Strom J, Frater RWM: Fatigue-induced failure of the lonsecuShiley pericardiaI xenograft in the mitral position. J THORAC CARDIOVASC SURG 87:836-844, 1984 40 Gabbay S, Bortolotti U, Wasserman F, Tindel N, Factor SM, Frater RWM: Long-term follow-up of the IonescuShiley mitral pericardiaI xenograft. J THORAC CARDlO· VAse SURG 88:758-763, 1984

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41 Ionescu MI, Tandon AP, Saunders NR, Chidambaram M, Smith DR: Clinical durability of the pericardia I xenograft valve: II years' experience, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 42-60 42 Cosgrove OM, Lytle BW, Gill CC, Golding LAR, Stewart RW, Loop FD, Williams GW: In vivo hemodynamic comparison of porcine and pericardia I valves. J THORAC CARDIOVASC SURG 89:358-368, 1985 43 Walker OK, Scotten LN, Modi VJ, Brownlee RT: In vitro assessment of mitral valve prostheses. J THORAC CARDIOVASC SURG 79:680-688, 1980 44 Walker OK, Brownlee RT: New-generation tissue valves. Their in vitro function in the mitral position. J THORAC CARDIOVASC SURG 88:573-582, 1984 45 Arbustini E, Jones M, Moses RD, Eidbo EE, Carroll RJ, Ferrans VJ: Modification by the Hancock T6 process of calcification of bioprosthetic cardiac valves implanted in sheep. Am J Cardiel 53: 1388-1396, 1984 46 Fuster V, Pumphrey CW, McGoon MD, Chesebro JH, Pluth JR, McGoon DC: Systemic thromboembolism in mitral and aortic Starr-Edwards prostheses: 1O-19-year follow-up. Circulation 66:Suppl I: 157-161, 1982 47 Gallo I, Ruiz B, Nistal F, Duran CM: Degeneration in porcine bioprosthetic cardiac valves. Incidence of primary tissue failure among 938 bioprostheses at risk. Am J Cardiol 53: 1061-1065, 1984 48 Klovekorn WP, Struck E, Holper K, Meisner H, Sebening F: Causes of valve failure and indications for reoperation after bioprosthetic cardiac valve replacement, Cardiac Bioprostheses. Proceedings of the Second International Symposium, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, pp 530-538

Discussion DR. EDW ARD A. SMELOFF Sacramento. Calif

We all continue to follow the performance of the various generations of tissue valves with a great deal of interest and concern. Central flow and low profile are frequently used buzz words in discussing valve preferences. Despite these subtle variations, the major considerations concerning prosthetic valve selection revolve about durability and valve-related complications. As yet no mechanical device, whether it contain a tissue valve or be a totally mechanical prosthesis, is free of thromboembolic complications necessitating varying uses of anticoagulation in varying centers. That the incidence of these complications is low should not deter us from searching for a better prosthesis. However, it also should not keep us from offering to our patients a prosthesis with proven and predictable long-term results. Although the mortality from repeat valve replacement is low in competent surgical centers, the anxiety and morbidity surrounding projected repeated replacements every 6 to 10

The Journal of Thoracic and Cardiovascular Surgery

years cannot be treated casually, especially when alternatives exist. Dr. Jamieson's group is reporting the early results in a large number of patients with the most recent modification of the Carpentier-Edwards porcine prosthesis-the supra-annular model. This work is.a continuation of the authors' extensive evaluation of the standard Carpentier-Edwards prosthesis, begun in 1976 and published in this JOURNAL in 1984. A comparison of these studies is pertinent. The performance of this new valve after a short interval seems at least as good as that of the previous model. It is hoped that the new design and different methods of fixing the valve will provide the desired decrease in incidence of tissue failure. Comparing the results of the Hancock and Carpentier valves, as Joyce and Nelson have done, increases optimism that tissue failure rate will decrease. These authors found a 5.9% explantation rate for the Hancock valve, compared to none for the Carpentier-Edwards standard valve. Similarly, it seems that thromboembolic rates were also diminished. One large note of caution, however, must be observed in evaluating these nonconcurrent studies done in separate institutions, because even sequential studies in the same institution are subject to the variabilities related to time frame and patient mix. Besides comparing large variable clinical series with their inherent biases, we should also carefully review well-done in vitro flow and stress analyses, such as those presented by Walker and Brownlee and others, and we should consider the long-term durability in the selection of our prosthesis of choice. I have several questions for the authors. Have you compared in vivovalve function in your two groups by catheterization or Doppler echo studies showing gradients and the incidence of regurgitation? Have you examined the explanted valves by electron microscopy for structural changes? What role, if any, did patient selection play in the valve type implanted, and who participated in the selection besides the surgeon? Did the cardiologist participate and, importantly, did the patient participate? Last, do you identify any predictable significant advantage of this supra-annular porcine prosthesis over the previous model? DR. JAMIESON (Closing) Dr. Smeloff, I thank you for your comments on this paper and your overall review of tissue prostheses. We have not compared the in vivo function of the standard valve and the supra-annular valve, although we have recatheterized a number of patients with the supra-annular prosthesis. In comparing our data to Dr. Chaitman's data from the Montreal Heart Institute, we found that the supra-annular valve performed better than the standard valve. A year ago at this meeting, Dr. Cosgrove presented data on intraoperative gradients that also showed that the supra-annular valve performed better than the standard valve. He now has shown that the Edwards pericardial valve performs better than both

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those valves. Thus, this valve appears to have superior hemodynamic properties. We have actually explanted only one valve (for endocarditis) and thus we have not had any opportunity to evaluate explanted valves. The other two patients we operated on had a periprosthetic leak and both of those leaks were repaired. With regard to patient selection, we obviously must be biased in our center. There are 11 operating surgeons at two hospitals. We do explain the potential opportunities to the patient and the disadvantages for both mechanical and tissue valves. For whatever reason, the majority of patients say, "I want a tissue valve. I do not want to be on long-term anticoagulants. I am not necessarily afraid of a reoperation in the future." Interestingly enough, we recently had a patient who wanted a tissue valve before she came into hospital. She was put in the same room as a patient who was having a reoperation, and she changed her mind 2 hours before the operation and requested a mechanical valve. We believethe advantages of a supra-annular valve include superior hemodynamics. Also, the valve is fixed under low pressure, and we do not think biological valves fixed under

Carpentier-Edwards supra-annular porcine valve 5 6 5

high pressure should be implanted. I think this is the main reason for our group selecting the supra-annular valve. We are confident that the lower pressure-fixed prosthesis, shown to be superior by Broom and Barratt-Boyes, is the advantageous tissue valve to implant. Although we used tissue valves in approximately 98% of our valve implantations until a year or so ago, as we began explanting more and more of our standard valves, we changed our practices somewhat. We now implant mechanical valves in approximately 20% of our patients, primarily in younger patients and those having reoperations. Some of the data in our institution on primary tissue failure in various age groups are as follows: In patients less than 18 years, our reoperation rate for primary tissue failure is 7.7% per patient-year, in those between 19 and 35, it is 2.3% per patient-year, and in those over 35, it is very low, 0.3% per patient-year. These figures are influencing our patient selection at present. We are avoiding implantation in younger patients unless they are in the late teens and early twenties. When they are female and wish to bear children in the near future, we are continuing to implant biological prostheses.