J. Y. Jung, M.D., A. G. Fabaz, D.O., P. Michael McFadden, M.D., Betty Lewis, R.N., and George Daughters, M.S.

Transcription

1 Five-Year Experience with the Ionescu-Shiley Bovine Pericardial Valve in the Aortic Position Lorenzo Gonzalez-Lavin, M.D., Seong Chi, M.D., T. Calvin Blair, M.D., J. Y. Jung, M.D., A. G. Fabaz, D.O., P. Michael McFadden, M.D., Betty Lewis, R.N., and George Daughters, M.S. ABSTRACT Between February, 977, and April, 982, 68 patients underwent aortic valve replacement (AVR) with an Ionescu-Shiley bovine pericardial valve. Concomitant procedures were performed in 7 patients. There were 2 hospital deaths (7.%). Among patients having AVR only, there were 5 deaths (5.2%). Assessment included valve durability, incidence of thromboembolism, clinical improvement, and patient survival. There was 00% follow-up. Actuarial freedom from intrinsic valve failure at 5 years was 96.3 & 3.6%. Intrinsic valve failure occurred only once, 0.3 episodes per 00 patient-years. Four patients had thromboembolic complications. As for clinical status, 99.3% of surviving patients are in New York Heart Association Functional Class I or, including 79 patients with valve sizes 7,9, or 2 mm (56%). Among 3 late deaths, 9 were related to the cardiovascular system. Overall patient survival is 84.9? 4.7%. Among the 92 patients with isolated AVR, % are alive at the 5-year follow-up. If the incidence of valve failure is not altered in years to come, the durability of the Ionescu-Shiley bovine pericardial valve will surpass that of previous bioprostheses. The better hydraulic characteristics of the Ionescu-Shiley bovine pericardial valve coupled with clinical reports of excellent hemodynamics and low thrombogenicity* motivated us to initiate the routine use of this valve in February, 977, shortly after it became commercially available. In order to correctly evaluate the clinical *Ionescu M: Personal communication, 976. From the Departments of Cardiovascular Surgery, The Ingham Medical Center, Lansing, MI, and the Palo Alto Medical Clinic, Health Care Division of the Palo Alto Medical Foundation, Palo Alto, CA. Presented at the Nineteenth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 7-9, 983. Address reprint requests to Dr. Gonzalez-Lavin, Palo Alto Medical Clinic, 300 Homer Ave, Palo Alto, CA performance of this bioprosthesis in the aortic position, we analyzed our 5-year experience. That analysis, which represents one of the longest follow-ups in the United States, is the focus of this report. Material and Methods Between February, 977, and April, 982, 68 patients underwent aortic valve replacement (AVR) with the Ionescu-Shiley bovine pericardial valve at the Ingham Medim Center, Lansing, MI, and the Palo Alto Medical Clinic, Palo Alto, CA. One hundred six patients were male and 62 were female, a.7: ratio. The mean age was 62.5 years, ranging from I7 to 85 years. Classified according to the criteria set forth by the New York Heart Association (NYHA), 3 patients (.8%) were in Functional Class I; 44 (26.2%) were in Class ; 98 (58.3%) were in Class ; and 23 (3.7%) were in Class IV. Therefore, 72% of the patients had been or were in congestive heart failure at the time of operation. Ten patients (6%) had hald previous cardiac procedures. In 4 patients, PLVR was under- taken in the presence of acute infective endocarditis (2.4% ). Eighty-seven patients (5.8%) were operated on an elective basis and 5 patients (8.9%), either in low cardiac output or in frank pulmonary edema, on an emergency basis. In 66 patients (39.3%), the indications for valve replacement were considered urgent because of rapid and progressive clinical deterior(ation. One hundred six patients (63.%) had predominant aortic stenosis, 30 (7.8%) had #aortic regurgitation, and in the other 32 (9%) there was mixed aortic valve disease. Concomitant procedures were performed in 7 patients (4:2.3%)(Table ). Cardiopulmonary bypass was employed with a bubble oxygenator using hemodilution, moderate flows, and moderate systemic hypothermia at 28 C. Crystalloid potassium cardioplegia 270

2 27 Gonzalez-Lavin et al: AVR with Ionescu-Shiley Bovine Pericardial Valve Table. Concomitant Procedures in 7 Patients Procedure MYOCARDIAL Coronary artery bypass 42 + Coronary endarterectomy Left ventricular aneurysmectomy Left ventricular aneurysmectomy VALVULAR No. of Patients" Total 45 (26.8%) Mitral valve replacementb Myomectomy + Resection of ascending aortic aneurysm + Coronary artery bypass Replacement mitral valve prosthesisb + closure of subannular aneurysm Mitral valve annuloplasty + coronary artery bypass Mitral commissurotomy Tricuspid annuloplasty Total MISCELLANEOUS (.9%) Myotomy 3 Resection of ascending aortic 3 aneurysm Total 6 (3.6%) "Numbers in parentheses represent percentages of all 68 patients. btypes of mitral valve prosthesis inserted included 8 Hancock, 4 Carpentier, and 4 Ionescu-Shiley bovine pericardial valves. at 4"C, as well as topical hypothermia, was used for myocardial protection. The standard technique for insertion of the aortic valve consisted of multiple interrupted mattress stitches of 3-0 Dacron reinforced with Teflon pledgets. Valve sizes used ranged from 7 to 3 mm: 7 mm, 8 patients; 9 mm, 28 patients; 2 mm, 54 patients; 23 mm, 44 patients; 25 mm, 23 patients; 27 mm, 8 patients; and 29 to 3 mm, 3 patients. Patients undergoing isolated AVR were not placed on anticoagulants. Patients undergoing multivalve replacement were put on a regimen of dicumarol after operation only if they were in chronic atrial fibrillation or had left atrial or ventricular clots. They usually remained on longterm therapy. Results Hospital Mortality Twelve patients died in the hospital (7.% hospital mortality). None of these deaths was valve related. Seven occurred in patients undergoing concomitant procedures for coronary artery disease. Among the 97 patients undergoing isolated AVR, 5 died (5.2% hospital mortality) (Table 2). Follow-up and Actuarial Analysis The fate of all 56 patients discharged from the hospital was ascertained, a 00% follow-up. A computerized questionnaire was completed following examination of the patient by the cardiologist or cardiac surgeon and also after telephone interview with the referring physician, or the patient, or both. The cumulative duration of follow-up is 304 patient-years or 3,648 patientmonths, with a minimum of 4 months and a maximum of 5Y4 years. The mean follow-up is 2 months. Forty-five patients (28.8%) have been followed at least 3 years. Actuarial curves were constructed according to the method of Kaplan and Meier [l] to compensate for censored observations. Censoring of data was by date of analysis. There have been no patients lost to the study whose status might change mortality figures as well as other variables studied in this group of patients. Statistical comparison of actuarial data was made using the method proposed by Gehan [2] when complete data were available (i.e., the results of the present study), and an estimate was made of the normalized Gehan score when comparing our data with other (published) data. Late Mortality Among the 56 patients discharged from the hospital, 3 died during the follow-up period (8.3% late mortality). Nine died of causes related to the cardiovascular system: 7 died of infective endocarditis (5 with and 2 without valve involvement), died of myocardial infarction, and died of left ventricular failure. Among the remaining 4 patients, each died of oat cell carcinoma of the lung, cirrhosis of the liver, agranulocytosis, and hepatitis. None of the deaths were valve related in the absence of infective endocarditis. Late mortality for those patients

3 272 The Annals of Thoracic Surgery Vol 36 No 3 September 983 Table 2. Hospital Mortality Valve Replacement Isolated Aortic with Concomitant Valve Replacement Procedures All 68 Cause of Death (N = 97) (N = 7) Patients Myocardial infarction 3 4 Low cardiac output Arrhythmia Renal failure 0 Rupture of right ventricle 0 Septic shock 0 Total 5 (5.2%) 7 (9.9%) 2 (7.%) discharged from the hospital following isolated AVR was 5.4% (5 patients), whereas it was 2.5% (8 patients) for those who had undergone concomitant procedures. L! =- 3 - P Valve Durability " 80-5 Bioprosthetic failure resulting from structural deterioration without preceding infection that required reoperation or resulted in death was l! ~0 ;, ( 0.3 episodes per 00 patient years ) *3.6% failure due to infection was not considered intrinsic failure, as the mechanism of infective endocarditis is more closely related to the host, or environment, than to the valve substitute per se [3,4]. Intrinsic valve failure occurred only once and was due to calcification (0.3 episodes per 00 patient-years). The patient involved was a 47- year-old man who was operated on initially for aortic regurgitation secondary to healed endocarditis. At the time of hospital admission, he had normal serum calcium values and no evidence of chronic renal failure. The valve failed 38 months after operation. Disruption, tear, or perforation of the leaflets has not been encountered. The actuarial freedom from valve failure at 5 years was 96.3? 3.6% (Fig ). Infective Endocarditis Infective endocarditis occurred in 0 patients (3.3 episodes per 00 patient-years). Among these 0 patients, 3 are alive and well, 2 with normal function of the bioprosthesis and after replacement of the infected bioprosthesis. The other 7 died of the infection; 5 had infective involvement of the prosthesis (3 following replacement of the original bioprosthesis). Years After Operation Fig. lntrinsic valve failure occurred only once (0.3 episodes per 00 patient-years) and 7uas due? to calcification. The actuarial curve depicts freedom from intrinsic valve failure at 5 years to be 96.3? 3.6%. Disruption, tear, or perforation of the leaflets has not been errcountered. Thromboembolism Thromboembolism-defined as all new focal neurological deficits, either transient or permanent, as well as all clinically detectable noncerebral arterial emboli-occurred in 4 patients (.3 episodes per 00 patient-years). One episode occurred early; this patient had experienced several episodes of atrial fibrillation alternating with sinus rhythm and a saddle embolus on the fifth postoperative day. In addition, the cannulation site of his friable ascending aorta had been repaired with several Teflon feltreinforced sutures. Three patients had late emboli ( episode per 00 patient-years). Two of these patients with concurrent mitral valve disease had an embolic episode at 20 and 36 months in spite of anticoagulant therapy with dicumarol. One of these patients had undergone concomitant mitral valve replacement with a porcine valve and Dacron

4 273 Gonzalez-Lavin et al: AVR with Ionescu-Shiley Bovine Pericardial Valve * O i ) (one episode per 00 patient years) Years After Operation 5 Fig 2. Actuarial event-free curve for thromboembolism. Three patients had a late thromboembolic episode ( episode per 00 patient-years). On the actuarial curve, 95.6? 2.6% of the patients are free from thromboembolism at 5 years. graft replacement of an ascending aortic aneurysm; the other had unrelieved mitral stenosis proven by postoperative cardiac catheterization. The third patient had a retinal embolus at 24 months. None of the thromboembolic episodes was fatal. A neurological deficit persisted only in the patients with concurrent mitral valve disease. The actuarial curve (Fig 2) shows that 95.6% t 2.6% of the patients are free from thromboembolism. Pa tien t S u rviva I Of the 56 patients discharged from the hospital, 84.9 t 4.7% are alive and retain their original Ionescu-Shiley bovine pericardial valve up Fig 3. Actuarial survival of all 56 patients discharged from the hospital and retaining the original bioprosthesis compared with the curve for the 92 patients undergoing isolated aortic valve replacement (AVR). to 5 rears after eration. When cc sidering the 92 patients who underwent isolated AVR, 87.8 k 5.9% are alive and well and have retained the original valve up to 5 years (Fig 3). Clinical Performance All surviving patients have shown a marked clinical improvement. One hundred forty or 99.3% are in NYHA Functional Class I or ; 68.8% (97 patients) had been or were in congestive heart failure at the time of operation (Fig 4). Of the 79 survivors who received either a 7, 9, or 2 mm valve, all are in Class I or ; 75.9% had been or were in congestive heart failure at the time of operation (Fig 5). In no instance was aortic root tailoring or the Konno procedure performed or a left ventricular apicoaortic conduit placed. Comment Biological tissue valves have been in clinical use since 962. Following the clinical acceptance of the aortic valve homograft [5-9, the field expanded to autologous tissue valves [lo, and later to xenograft valves [2, 4. ISOLATED AVR _ P I Year8 Alter Operation 9*4.7% A U PATIENTS

5 274 The Annals of Thoracic Surgery Vol 36 No 3 September 983 OPERATION li" i* T 99. T I I AFTER OPERATION 3".. Fig 4. Preoperative and postoperative New York Heart Association Functional Classification of the 4 patients now alive with the Ionescu-Shiley bovine pericardial valve in the aortic position shows a striking improvement (p < 0.00). OPERATION T T I I I " I I AFTER OPERATION m'r. J Fig 5. Preoperative and postoperative New York Heart Association Functional Classification of the 79 survivors who received either a 7, 9, or 2 mm valve. At the time of operation, 75.9% had been or were in congestive heart failure. All are now in Class I or II (p < 0.00). Because of its availability and relatively low thrombogenicity, the porcine xenograft valve established itself as a prototype for tissue valves [5-8. Within the last few years, however, there has been some concern about use of this valve [7, 9-2]; its long-term durability has come into question with reports that there is a tenfold increase in primary tissue failure between the fifth and sixth year of the follow-up [7]. In addition, it is known that porcine valves implanted in growing individuals have a high rate of calcification 22 and that small-sized valves have important residual gradients [23-25 in spite of modifications [26]. A different approach to the development of biological tissue valves has been pursued by the Leeds group since 97 [27]. Glutaraldehydestabilized bovine pericardium has been utilized to construct a trileaflet valve. The hydraulic characteristics of this man-made valve with a central nonimpeded blood flow and larger orifice than other bioprostheses give superior hemodynamics, with appreciable lesser residual gradients as shown in vitro [28-30 and in clinical assessments [3-34. The symmetrical opening and closing of three identical leaflets markedly reduces blood turbulence. This, in turn, decreases the likelihood of thrombus formation. Attracted by these characteristics, we began to use the Ionescu-Shiley bovine pericardial valve routinely for AVR in 95'7 and 5 years later, we evaluated its performance. Four variables were analyzed: valve durability, incidence of thromboembolism, clinical improvement, and overall patient survival.. Valve durability at 5 years is excellent, with only one incident of calcification. No tears or perforations of the leaflets have been encountered. Durability in our :series is 96.3 & 3.6%, which is similar to thlat reported by Ionescu and associates [35] as depicted in actuarial form (Fig 6). 2. Thromboembolism has been low without routine anticoagulant therapy. Through the fifth year of this study, 95.6 k 2.6% of all survivors are free from throniboembolism. 3. The clinical performance of this valve has been excellent, corroborating the in vitro studies as well as the hemodynamic

6 275 Gonzalez-Lavin et al: AVR with Ionescu-Shiley Bovine Pericardial Valve I (0.3 episodes per 00 patient years i Years After Operation 7 9 Fig 6. Actuarial curves of valve durability comparing the present series with one reported by lonescu and colleagues 35. assessments by Ionescu and Tandon [33] and Becker [3], Ott [34], Garcia-Bengochea [32], and their associates. All but 2 of our patients have improved markedly (see Fig 4). We have been particularly interested in the status of patients with a small annulus. Ninety patients (53.6%) received a valve size between 7 and 2 mm in diameter. All 79 survivors have shown marked improvement in exercise tolerance (see Fig 5). Aortic root tailoring, Konno procedures, or the use of a left ventricular apicoaortic conduit has not been necessary. 4. Although valve durability is an important determinant, patient survival depends on several factors. They include not only those as- sociated with the valve per se, but also those concerning the type of population in a given study, such as age, concurrent important diseases, concomitant procedures, and degree of myocardial reserve (Table 3). Patients in NYHA Class I or IV before operation had a shorter survivorship (p < 0.02). Of all 56 patients leaving the hospital, 84.9 & 4.7% are alive and retain their original Ionescu-Shiley bovine pericardial valve up to 5 years postoperatively. Of the 92 patients who underwent isolated AVR, 87.8 k 5.9% are alive and well up to 5 years after operation. Figure 6 reveals a similarity of results between two series using Ionescu-Shiley bovine pericardial valves [35]. Thus, this survival (whether in isolated replacement or grouped with concomitant procedures) is comparable to available statistics using other types of valve substitutes [9, 20, 36-39]. Table 3. Survival According to Preoperative New York Heart Association Functional Classification Overall Preop. NYHA Survivorship Functional No. of Hospital Late (% of Patients Class Patients Mortality Mortality Operated On) I II I N Total 68 2 (7.%) 3 (7.7% or 8.3% of 56 patients 85.a released from hospital) "Includes 2 patients who required reoperation and survived. NYHA = New York Heart Association.

7 276 The Annals of Thoracic Surgery Vol 36 No 3 September 983 Our experience with the Ionescu-Shiley bovine pericardial valve outlines its durability and function as well as the thromboembolic rate during a 5-year period. The characteristic that remains to be defined is its eventual longer-term durability. In the field of biological tissue valves, long-term durability has been directly related to the structural changes of the given tissue after the process of sterilization or stabilization [40, 4. Unlike previous biological tissues used in valve substitutes, bovine pericardium consists of three layers-the serosa, fibrosa, and epipericardium [42]-with two important features: waviness of the collagen fibrils within each bundle and multidirectional orientation of the bundles. The spongiosa layer found in the porcine valve tissue structure [43] is not present. This layer develops free spaces after processing that are believed to be where deposition of plasma protein, blood elements, and calcium phosphate are most likely to occur [43], and the absence of the layer is a theoretical advantage of bovine pericardium [42]. The collagen structure of bovine pericardium is not modified by the methods of stabilization and sterilization; the waviness is preserved. This waviness is believed to be important in equalizing the distribution of the mechanical forces that are applied to collagen during the opening and closing of the valve leaflets [MI. In addition, the multidirectional arrangement of the collagen fibers in treated bovine pericardium may be important in the preservation of the structural integrity of a given biological tissue and may contribute to the long-term durability of tissue valves [42]. These structural characteristics suggest, at least on a theoretical basis, that glutaraldehyde-stabilized bovine pericardium should be expected to have a long-term functional capability. The 0-year report by Ionescu and colleagues [45] seems to corroborate such structural advantages. From the practical point of view, we believe that we are now at the crossroads in follow-up of the bovine pericardial valve. In a comparison between the first 5 years with that valve and the porcine xenograft valve, both actuarial curves of valve durability are similar. However, after the fifth and sixth year, the porcine valves have shown an increasing incidence of intinsic tissue failure [7, 20, 2. The following few years should demonstrate the difference in durability of these two valves, if such a difference exists. Continuing careful analysis of our group of patients will allow us to quantitate the true longterm durability of the Ionescu-Shiley bovine pericardial valve. We conclude from the present experience that the Ionescu-Shiley bovine pericardial valve in the aortic position has excellent durability and function for 5 years, with a low incidence of thromboembolism without routine use of anticoagulants. The valve function assessed by clinical performance of our patients, has been outstanding, particularly in those patients with a small aortic annulus. Use of this valve in the latter group is highly recommended. If the present incidence of intrinsic tissue failure is not altered in the years to come, the durability of this valve will be well established, corroborating the reports and prediction of Ionescu and associates [45] and surpassing the durability and long-term function of previous bioprostheses. The authors thank Win Vetter for secretarial assistance in the preparation of this manuscript. References. Kaplan EL, Meier P: Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457, Gehan EA: A generalized Wilcoxon test for comparing arbitrarily singly-censored samples. Biometrika 52:203, Borkon AM, McIntosh CL, Von Rueden TJ, Morrow AG: Mitral valve replacement with the Hancock bioprosthesis: five- to ten-year follow-up. Ann Thorac Surg 32:27, Tandon AP, Whitaker W, Ionescu M: Multiple valve replacement with pericardial xenograft: clinical haemodynamic study. Br Heart J 44:534, Barratt-Boyes BG: Homograft aortic valve replacement in aortic incompetence and stenosis. Thorax 9:3, Gonzalez-Lavin L, Ross DN: Homograft aortic valve replacement: report of a five-year experience at the National Heart Hospital, London. J Thorac Cardiovasc Surg 60:, Hoeksema TD, Titus JL, Giuliani ER, Kirklin JW: Early results of use of homografts for replacement of the aortic valve in man. Circulation 35:Suppl :9, Malm JR, Bowman FO Jr, Harris PD, Kowalik

8 277 Gonzalez-Lavin et al: AVR with Ionescu-Shiley Bovine Pericardial Valve ATW: An evaluation of aortic valve homografts sterilized by electron beam energy. J Thorac Cardiovasc Surg 54:47, Ross DN: Homograft replacement of the aortic valve. Lancet 2:487, Gonzalez-Lavin L, Geens M, Somerville J, Ross DN: Autologous pulmonary valve replacement of the diseased aortic valve. Circulation 42:78, 970. Ross DN: Replacement of the aortic and mitral valves with a pulmonary autograft. Lancet 2:956, Binet JP, Durgn CG, Carpentier A, Langlois J: Heterologous aortic valve transplantation. Lancet 2:275, Carpentier A, Lemaigre G, Robert L, et al: Biological factors affecting long-term results of valvular heterografts. J Thorac Cardiovasc Surg 58:467, Zuhdi N, Hawley W, Voehle V, et al: Porcine aortic valves as replacements for human heart valves. Ann Thorac Surg 7:479, Cohn LH, Koster JK, Mee RBB, Collins JJ Jr: Long-term followup of the Hancock bioprosthetic heart valve: a 6-year review. Circulation 6O:Suppl :87, Davila JC, Magilligan DJ Jr, Lewis JW Jr: Is the Hancock porcine valve the best cardiac valve substitute today? Ann Thorac Surg 26:303, Oyer PE, Miller DC, Stinson EB, et al: Clinical durability of the Hancock porcine bioprosthetic valve. J Thorac Cardiovasc Surg 80824, Reis RL, Hancock WD, Yarbrough JW, et al: The flexible stent: a new concept in the fabrication of tissue heart valve prostheses. J Thorac Cardiovasc Surg 62:683, Angell WW, Angell JD, Kosek JC: Twelve-year experience with glutaraldehyde-preserved porcine xenograft. J Thorac Cardiovasc Surg 83:493, Craver JM, Jones EL, McKeown P, et al: Porcine cardiac xenograft valves: analysis of survival, valve failure, and explantation. Ann Thorac Surg 34:6, Magilligan DJ Jr, Lewis JW Jr, Jara FM, et a Spontaneous degeneration of porcine bioprosthetic valves. Ann Thorac Surg 30259, Geha AS, Laks H, Stansel HC Jr, et al: Late failure of porcine valve heterografts in children. J Thorac Cardiovasc Surg 78:35, Craver JM, King SB, Douglas JS, et al: Late hemodynamic evaluation of Hancock modifiedorifice aortic bioprosthesis. Circulation 6O:Suppl :93, Lurie AJ, Miller RR, Maxwell KS, et al: Hemodynamic assessment of the glutaraldehydepreserved porcine heterograft in the aortic and mitral positions. Circulation 56:Suppl2:04, Ubago JL, Figueroa A, Colman T, et al: Hemodynamic factors that affect calculated orifice areas in the mitral Hancock xenograft valve. Circulation 6:388, Rossiter SJ, Miller DC, Stinson EB, et al: Hemodynamic and clinical comparison of the Hancock modified orifice and standard orifice bioprostheses in the aortic position. J Thorac Cardiovasc Surg 8054, Ionescu MI, Tandon AP, Mary DAS, Adid A: Heart valve replacement with the Ionescu-Shiley pericardial xenograft. J Thorac Cardiovasc Surg 73:3, Gabbay S, McQueen DM, Yellin EL, et al: In vitro hydrodynamic comparison of mitral valve bioprostheses at high flow rates. J Thorac Cardiovasc Surg 76:77, Rainer WG, Christopher RA, Sadler TR Jr, Hilgenberg AD: Dynamic behavior of prosthetic aortic tissue valves as viewed by high-speed cinematography. Ann Thorac Surg 28:274, Wright JTM: Hydrodynamic evaluation of tissue valves. In Ionescu MI (ed): Tissue Heart Valves. London, Butterworth, 979, pp Becker RM, Strom J, Frishman W, et al: Hemodynamic performance of the Ionescu-Shiley valve prosthesis. J Thorac Cardiovasc Surg 80:63, Garcia-Bengochea JB, Siebert MF, Carreno CI, et al: Clinical experience with the Ionescu-Shiley xenograft valve: four to five yew followup. Tex Heart Inst J 9:285, Ionescu MI, Tandon AP: The Ionescu-Shiley pericardial xenograft heart valve. In Ionescu MI (ed): Tissue Heart Valves. London, Butterworth, 979, pp Ott DA, Coelho AT, Cooley DA, Rue GJ Jr: Ionescu-Shiley pericardial xenograft valve: hemodynamic evaluation and early clinical follow-up of 326 patients. Cardiovasc Dis (Bull Tex Heart Inst) 737, Ionescu MI, Silverton NP, Tandon AP: Clinical durability of the pericardial xenograft valve, eleven years experience. In Cooley DA (ed): Proceedings of the Cardiac Prostheses Symposium, Pebble Beach, CA, Aug 30-3, 98. (in press, 983) 36. Cheung D, Flemma RJ, Mullen DC, et al: Tenyear follow-up in aortic valve replacement using the Bjork-Shiley prosthesis. Ann Thorac Surg 32:38, Karp RB, Cyrus RJ, Blackstone EH, et al: The Bjork-Shiley valve: intermediate-term follow-up. J Thorac Cardiovasc Surg 8:602, Teply JF, Grunkemeier GL, Sutherland H DA, et al: The ultimate prognosis after valve replacement: an assessment at twenty years. Ann Thorac Surg 32:, Williams JB, Karp RB, Kirklin JW, et al: Considerations in selection and management of patients undergoing valve replacement with glutaralde-

9 278 The Annals of Thoracic Surgery Vol 36 No 3 September 983 hyde-fixed porcine bioprostheses. Ann Thorac Surg 30:247, Gonzalez-Lavin L, Al-Janabi N, Ross DN: Longterm results after aortic valve replacement with preserved aortic homografts. Ann Thorac Surg 3:594, Gonzalez-Lavin L, O Connell TX: Mitral valve replacement with viable aortic homograft valves. Ann Thorac Surg 5:592, Ishihara T, Ferrans VJ, Jones M, et al: Structure of bovine parietal pericardium and of unimplanted Ionescu-Shiley pericardial valvular bioprostheses. J Thorac Cardiovasc Surg 8:747, Ferrans VJ, Boyce SW, Billingham ME, et al: Calcific deposits in porcine bioprostheses: structure and pathogenesis. Am J Cardiol46:72, Broom ND, Thomson FJ: Influence of fixation conditions on the performance of glutaraldehyde-treated porcine aortic valves: towards a more scientific basis. Thorax 34:66, Ionescu MI, Smith DR, Hasan SS, et al: Clinical durability of the pericardial xenograft valve: ten years experience with mitral valve replacement. Ann Thorac Surg 34:265, 982 Discussion DR. CONRAD PELLETIER (Montreal, PQ, Canada): I congratulate the authors on their fine data and timely report of their experience with pericardial xenografts. At the Montreal Heart Institute, we have accumulated a large experience with the Carpentier- Edwards porcine valve, which we have implanted in 780 patients since 976. Among the 20 patients operated on more than 5 years ago, the actuarial survival is 72% at 6 years. All survivors have been followed and 98% of them are in New York Heart Association Class I or. The rate of primary tissue failure of the valve is 0.6 per 00 patient-years, with a probability of freedom from such failure of 96% after 6 years. The incidence of endocarditis has been very low-0.4 per 00 patient-years. Reoperation for valve dehiscence was required in 3 patients. There was an overall incidence of thromboembolic complications of.5 per 00 patient-years. These results are very similar to those reported by Dr. Gonzalez-Lavin and his colleagues with the Ionescu-Shiley pericardial valve, although follow-up in the latter study has averaged less than 2 years. I note a higher incidence of endocarditis in the authors series, and I would like Dr. Gonzalez-Lavin to comment on this. I also wish to ask him about the incidence of reoperation and perivalvular leaks in the series, since these also must be considered valverelated complications. Finally, there is a striking difference between our study and that of Dr. Gonzalez-Lavin s group in regard to the valve size used most often in the aortic position. In our experience with the Carpentier- Edwards valve, a stent size smaller than 23 mm has been implanted only rarely, accounting for 6% of valves in the aortic position; on the other hand, smallsized valves were used in 54% of the Ionescu-Shiley implants. We do not use aortic enlargement techniques. Such a difference may have solme relevance in comparing the hemodynamic performance of these two bioprostheses, since the disparity could be due to the sizing of the valve stent or to the shape of the sewing ring. I ask Dr. Gonzalez-Lalvin s views on this. DR. DENTON COOLEY (Houston, TX): Our experience with the Ionescu-Shiley valve dates back about four and one-half years. During this time we have operated on 2,462 patients and replaced the aortic valve in,293 of them. In the same period, we also have done 936 mitral valve replacements and more than 200 combined aortic and rriitral valve replacements. Before April, 982, we implanted 597 Ionescu- Shiley valves; therefore, the follow-up period was a minimum of almost one year. During that same period, other types of valves, mostly mlechanical, were used in 22 instances. Among the synthetic valves used were the Bjork-Shiley, Cooley-Cutter, and St. Jude prostheses. We have elected to use Ionescu- Shiley valves in older patients because of the shorter life expectancy and concern about the ultimate durability of the valve. The operative mortality in patients undergoing aortic valve replacement was 2.5%. F or those having concomitant procedures, however, the mortality increased, so the overall mortality was 6.5%. Most of the deaths were patients who had cclncomitant coronary bypass procedures. In the total series, there were only 6 instances of thromboembolism, for an incidence of.4%. In patients having aortic valve replacement only, there were 8 late emboli. Most of our patients are not given anticoagulants unless there are mitigating reasons such as chronic atrial fibrillation or other problems that necessitate continued anticoagulation. Valve failure occurred in 5 of our p,atients. The predominant cause of aortic graft failure was calcification, which was seen in 5 patients; most were adolescents, but was a 46-year-old man. In a single valve, a split in a leaflet developed. We conclude that the Ionescu-Shiley bioprosthesis is a hemodynamically sound and rleliable valve for clinical use. DR. MARIAN I. IONESCU (Leeds, England): I wish to compliment the authors on an excellent surgical series and on their careful analysis and clear presentation of the results with pericardial xenograft valves in the aortic position. The marked clinical improvement reported by Dr. Gonzalez-Lavin and his colleagues in all patients, including those with small valve sizes (7, 9 and 2 mm), is evidently substantiated by the superior hemodynamic performance of this valve. In our own series of more than 900 pericar-

10 279 Gonzalez-Lavin et al: AVR with Ionescu-Shiley Bovine Pericardial Valve dial xenografts implanted since 97, 36 patients with aortic valve replacement underwent hemodynamic studies a mean of 4.2 months postoperatively. The peak-systolic gradient for the entire group was 6.4 mm Hg at rest and 9.6 mm Hg with exercise. For valves of 9 and 2 mm, the gradients were 8.3 and 7.9 mm Hg at rest and 3.3 and 2.3 mm Hg with exercise, respectively. The calculated valve areas for these two sizes were. and.4 cm2 at rest and.3 and.8 cm2 with exercise. The pericardial valve durability reported by Dr. Gonzalez-Lavin and his associates is very similar to our own data. The actuarial freedom from valve dysfunction for our entire series of aortic valve replacements was 96.? 2.0% at 5 years and 88.2? 6.9% at 2 years of follow-up. Separate analysis of the durability of the hospital-made valves (used between 97 and 976) and that of the Shiley-made valves (used since 976) has shown actuarial figures at 6 years of follow-up to be 93% for the former and 00% for the latter group. The results presented by Dr. Gonzalez-Lavin and his co-workers, along with similar data reported by other groups, support the view that the Shiley pericardial xenograft offers excellent durability at up to 6 years of follow-up. In addition, our experience with the hospital-made pericardial xenograft indicates that its durability will be sustained in at least 88% of patients at 2 years of follow-up. These data represent a major improvement in the continuous evolution of tissue heart valves. DR. D. s. SAKSENA (Bombay, India): Rheumatic heart disease continues to be a major problem in my part of the world, and my colleagues and I see a large number of very young patients who require valve replacement operations. The youngest patient we have operated on was 6 years old. We have been using the Ionescu-Shiley valve since 976 and have accumulated a large experience with this bioprosthesis. We agree with the conclusion of Dr. Gonzalez-Lavin and his colleagues that the Ionescu-Shiley valve performs satisfactorily in the aortic position. We do have certain reservations about it in the mitral position. One of the problems that has bothered us is prosthetic endocarditis, which has been seen in 8% of our patient population. In addition, we have had problems with calcification, thromboembolism, cusp rupture, and left ventricular outflow obstruction. We have used tailoring procedures of the aortic root in about 0% of our patients, primarily because the aorta is very small in most of them. I am concerned that Dr. Gonzalez-Lavin has used 7 mm valves, and I wish to ask him what the gradient is across such small valves. DR. w. GERALD RAINER (Denver, CO): I have enjoyed this paper and confirm most of the authors observations. Our series of pericardial valves in the aortic position numbers 28 at present. One hundred five of these are Ionescu-Shiley valves and 23 are Carpentier-Edwards valves; however, they are all pericardial leaflet valves. We have five years of follow-up in the Ionescu-Shiley group and one and one-half years of follow-up in the Carpentier-Edwards group. The results of our series are in greater agreement with those of Dr. Gonzalez-Lavin s group than with those of the Montreal investigators in that 50% of our valve implants in both the Ionescu-Shiley and the Carpentier-Edwards patients are in the 7, 9, and 2 mm sizes. In addition, our series is similar to that of Dr. Gonzalez-Lavin and his colleagues in that we have not utilized any root-enlarging procedures. The few problems that have been observed occurred in the Ionescu-Shiley group because we have had the longest experience with this particular valve. We have seen one embolus; that was in a patient in whom the valve was inserted in the presence of an acute bacterial endocarditis. We have seen two leaflet tears, one at 3 years, 3 months, and one at 4 years. Both of these were treated by rereplacement. We have seen two cases of infection: an enterobacterial infection occurring 4 years postoperatively and an a- hemolytic streptococcal infection occurring year postoperatively. Both were treated with antibiotics and cured with no aortic insufficiency, which I think attests to the ability of this particular tissue to resist infection from bacteremia. In examining the leaflet tears that we have seen, the disruption appears to start at the suture holes used in the original Ionescu-Shiley valve with a fixation suture inside the strut. Because of this, we now use a modified valve produced by Edwards Laboratories. I believe that Shiley Laboratories is producing a new version of their valve, currently under clinical investigation, with the same modification. In both valves, the leaflets are attached around the outside of the post and not on the inside, thus avoiding this potential fixation point for the beginning of a leaflet tear. DR. GONZALEZ-LAVIN: I thank the discussants for their kind comments. We probably do have the largest reported series of patients with 7 mm bioprostheses. I agree with Dr. Rainer that the patients in our series were probably not as robust as those in the Montreal series. For instance, the mean age of the patients was 75 years; the oldest patient in this group was 88. In response to Dr. Saksena s question, we have not yet done any postoperative hemodynamic studies. Clinically, however, the patients are doing very well. One plays golf twice a week, and several are very active in their social circles. In response to Dr. Pelletier s questions regarding the incidence of infective endocarditis, we initially were concerned that our patients were having more infections. However, after carefully analyzing this incidence, we found that it was related to the patient

11 280 The Annals of Thoracic Surgery Vol 36 No 3 September 983 population. At Ingham Medical Center, which is a referral center for the rural areas of Michigan, there is a large number of patients with acute infective endocarditis; we were not able to cure the infection after valve replacement because of the severity of the illness. The lack of antibiotic prophylaxis during dental manipulations after valve replacement also contributed to this incidence. Dr. Cooley, your experience with the Ionescu- Shiley valve is most impressive and further corroborates that results such as those reported by the Leeds group can be reproduced by other investigators in other large series of patients. I believe Dr. Rainer also has concurred with our conclusions. Last but not least, Mr. Ionescu, we are indebted to you for your pioneering work that has culminated with the development and construction of this reliable bioprosthesis. Thank you very much. Notice from the American Board of Thoracic Surgery The American Board of Thoracic Surgery will begin its recertification process in 984. Diplomates interested in participating in this examination should maintain a documented list of the cardiothoracic operations they performed during the year prior to application for recertification. They should also keep a record of their attendance at thoracic surgical meetings and other continuing medical education activities for the two years prior to application for recertification. In place of a cognitive examination, candidates for recertification will be required to complete both the general thoracic and cardiac portions of the SESATS (Self-Eiducation/Self- Assessment in Thoracic Surgery) I Syllabus. Diplomates whose 0-year certificates will expire in 986 may begin the recertification process in 984. Their new certificate will be dated 0 years from the time of expiration of the original certificate. Recertification is also open to any Diplomate with an unlimited ceriificate. The deadline for submission of applications is July,984. A recertification brochure outlining the rules and requirements for recertification in thoracic surgery is available on request from the American Board of Thoracic Surgery, 4640 E Seven Mile Rd, Detroit, MI