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Performance of the Hancock Porcine Bioprosthesis Following Aortic Valve Replacement: Considerations Based on a 15-Year Experience
Performance of the Hancock Porcine Bioprosthesis Following Aortic Valve Replacement: Considerations Based on a 15-Year Experience L
Aldo D. Milano, M.D., Uberto Bortolotti, M.D., Alessandro Mazzucco, M.D., Francisco Guerra, M.D., Giovanni Stellin, M.D., Enrico Talenti, M.D., Gaetano Thiene, M.D., and Vincenzo Gallucci, M.D. ABSTRACT All patients undergoing isolated aortic valve replacement with a standard Hancock porcine bioprosthesis (PB), from 1970 to 1983, were reviewed. There were 196 patients, 162 male and 34 female patients, with a mean age of 48 k 12 years. Operative survivors were followed up from 3 to 15.6 years (mean follow-up, 6.6 f 1.5 years), with a cumulative follow-up of 1,140 patient-years, being 100% complete. Actuarial survival was 51 f 15% at 14 years. Eight patients sustained systemic embolic episodes (0.7 f O.Z%/patient-year);actuarial freedom from emboli is 89.4 f 4.3% at 14 years. Reoperation was performed in 53 patients: in 6 because of endocarditis (0.5 f O.Z%/patientyear), in 7 because of perivalvular leak (0.6 f O.Z%/patientyear), and in 40 because of PB primary tissue failure (3.5k O.S%/patient-year). Actuarial freedom from PB-related deaths, PB failure, and overall PB-related complications at 14 years was 66.3 f 19, 34.3 f 11, and 30 f lo%, respectively. This long-term experience shows that the performance of the Hancock PB appears satisfactory up to 8 years, while it progressively deteriorates beyond 10 years because of the impact of primary tissue failure on valve durability, justifying the restriction of its use in the aortic position in selected patients. Although considerable experience has been accumulated on the implantation of the Hancock porcine bioprosthesis (PB), most of the information available is limited to the first 10 postoperative years [1-4]. The Hancock PB has been used clinically at our institution since the early 1970s [3]; therefore, in the present study we reviewed our 15-year experience with all patients who underwent isolated aortic valve replacement (AVR) to provide data for a more extended follow-up of this device.
Patients and Methods From March, 1970, to December, 1983, a total of 196 patients underwent AVR with the standard, glutaraldeFrom the Departments of Cardiovascular Surgery, Radiology, and Pathology, University of Padova Medical School, Padova, Italy. Accepted for publication Feb 9, 1988. Address reprint requests to Dr. Bortolotti, Istituto di Chirurgia Cardiovascolare, Universiti di Padova, Via Giustiniani, 2, 35128 Padova, Italy.
hyde-processed, flexible-stented Hancock PB (Hancock/ Extracorporeal Laboratories, Anaheim, CA). There were 162 male and 34 female patients, ranging in age from 17 to 70 years (mean age, 48 ? 12 years). Preoperatively, 29 patients were in New York Heart Association (NYHA) Functional Class XI, 149 were in Class 111, and 18 were in Class IV. The following list summarizes the indications for AVR: Rheumatic endocarditis Idiopathic calcific degeneration Myxomatous degeneration Infective endocarditis Congenital malformation Failing prosthesis
34.1% 33.1% 18.3% 7.6% 5.6% 1.3%
Figure 1 shows the distribution of PBs implanted according to size; in most of the patients the diameter of the valves ranged from 23 to 29 mm. Associated surgical procedures were performed in 29 patients (15%),including coronary artery bypass grafts in 10, resection of ascending aorta aneurysm in 11, mitral valvuloplasty in 7, and closure of a ventricular septa1 defect in 1.
n= 196 85
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S I Z E S Fig 1. Distribution of the aortic porcine bioprostheses (PB) implanted according to size.
216 Ann Thorac Surg 46216-222, Aug 1988. Copyright 0 1988 by The Society of Thoracic Surgeons
217 mano et ak Long-Term Follow-up of Porcine Valve Recipients
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Fig 2. Actuarial survival curve following aortic valve replwement with a Hancock bioprosthesis. Numbers on the horizontal axis indicate the number of patients at risk. Operative deaths are not included.
Summary of Postoperative Complications No. of
Event ~
~
%/Patient-
Patients
Year
44
3.8 +- 0.6
8 5 2 40 7 7
0.7 2 0.2 0.4 2 0.2 0.1 2 0.1 3.5 2 0.5 0.6 2 0.2 0.6 2 0.2
~~~
Late mortality Thromboemboli Overall Fatal
Anticoagulation-related hemorrhage Primary tissue failure Endocarditis Perivalvular leak
Surgical Technique and Follow-up All patients were operated on using standard cardiopulmonary bypass, moderate systemic hypothermia, topical cooling with or without coronary perfusion, and after 1977 with cold potassium cardioplegia. PBs were implanted with multiple interrupted sutures reinforced with Teflon subannular pledgets when indicated 13, 41. Orally administered anticoagulation was started usually on the second postoperative day; almost all patients were maintained on coumarin derivatives for only 3 months, unless otherwise decided by the referring cardiologist [3]. Follow-up was performed through direct patient evaluation or through questionnaires during a 6-month intervaliending in December, 1986. Cumulative duration of follow-up is 1,140 patient-years, ranging from 3 to 15.6 years (mean follow-up, 6.6 f 1.5 years) and is 100% complete. Explanted PBs underwent detailed morphological studies as described elsewhere [5].
Bioprosthesis-Related Complications Definitions of major and minor thromboembolic episodes, perivalvular leak, endocarditis, and PI3 primary tissue failure (PTF) in porcine valve recipients have been previously reported [3, 41. Anticoagulant-related hemorrhages were considered as any episode requiring treatment or hospitalization. According to the Stanford criteria [6], PB failure is considered as any of the afqrementioned complications causing death or requiring reoperation. Deaths caused by any of these complications or occurring at reoperation are considered PBrelated. Statistical Analysis Continuous variables are presented as means SD, and categorical variables are expressed as percentages with their 70% confidence limits (CL). Rates of patient survival, event freedom, and incidence of PB-related complications are expressed both by actuarial analysis [7] and by linearized rates as percentage per patient-year [8]. The actuarial curves do not include operative mortality, and values are presented as means SEM. Patients were included in the study until their PB was replaced, they died, or were lost to follow-up. Patients were removed from the study while still alive when their original PB was successfully explanted or when an additional valve replacement was performed.
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Results Patient Survival There were 23 operative deaths, with an overall mortality of 11.7% (9.3-14.6%, 70% CL). The cause of death was cardiac failure in 19 patients, postoperative hemorrhage in 2, cerebral damage in 1, and sepsis in 1. Of the 173 patients discharged from the hospital, 44 died during the follow-up period with a linearized rate of 3.8 O.b%/patient-year. The cause of late death was chronic cardiac failure in 12 patients, cerebral embolism in 5, malignancy in 3, prosthetic endocarditis without reoperation in 1, and chronic renal failure in 1. Nine patients died of low output syndrome at reoperation. Finally, the
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218 The Annals of Thoracic Surgery Vol 46 No 2 August 1988
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Fig 3. Actuarial freedom from thromboembolic events after aortic valve replacement.
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Fig 4. Actuarial freedom from primary tissue failure (PTF) after aortic valve replacement.
the fourth postoperative year. The linearized rate of thromboembolic episodes was 0.7 k 0.2%/patient-year, and the actuarial probability of being free from emboli at 14 years was 89.3 4.3% (Fig 3). Anticoagulant-related hemorrhages occurred in 2 patients (0.1 O.l%/patient-year), both of whom were receiving anticoagulant treatment because of chronic atrial fibrillation. Endocarditis occurred in 7 patients (0.6 t 0.2%/patient-year); reoperation was performed in 6 (0.5 -+ 0.2%/patient-year) of them from 1 to 64 months (mean time, 21.4 9.7 months) after AVR, with 4 deaths (66.6%; 37.8-88.5%, 70% CL). Reoperation for perivalvular leak was performed in 7 patients (0.6 t 0.2%/patient-year) from 1 to 93 months (mean, 19 12 months) after AVR, with no deaths.
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cause of death could not be determined in 13 patients. Actuarial survival at 14 years was 51 15% (Fig 2). Among the 88 long-term survivors, 52 are currently in NYHA Functional Class I and 36 are in NYHA Functional Class 11; 77 patients are in sinus rhythm, 9 are in atrial fibrillation, and 2 have an endocavitary pacemaker. Eleven patients (12.5%) are receiving orally administered anticoagulants, 3 (3.5%) are receiving only antiplatelet drugs, and 74 (84%)are not anticoagulated.
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PB-Related Complications The Table summarizes the PB-related complications. Thromboembolic events occurred in 8 patients during the follow-up period. Four of them were in atrial fibrillation, and 2 were on a long-term regimen of anticoagulants. Five patients sustained a fatal cerebral embolism. The majority of thromboembolic episodes occurred after
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*
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Incidence of Prima y Tissue Failure Primary tissue failure (PTF) led to reoperation in 40 patients after a mean interval of 6.8 2.3 years (range, 3.2-13.2 years), with a linearized rate of 3.5 0.5%/ patient-year. Overall mortality at reoperation for PTF was 12.5%(7.0-20.0%, 70% CL). Elective reoperation was per-
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219 Milano et al: Long-Term Follow-up of Porcine Valve Recipients
A
B formed in 38 patients, with 3 deaths (7.8%; 3.4-15.8, 70% CL), while 2 patients underwent emergency reoperation, and both died (100%; 39-loo%, 70% CL). Actuarial freedom from MT at 14 years was 40.8 12.7% (Fig 4). PTF was caused mainly by cusp calcification, leading usually to valve regurgitation due to commissural rupture or cusp perforation and tears (Figs 5 , 6). Occasionally, PTF was worsened by fibrous tissue overgrowth and inward bending of the stent posts [9] or by a dissecting intracuspal hematoma [lo].
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C
Fig 5. Gross view of an aortic Hancock porcine bioprosthesis explanted after 78 months because of marked incompetence. Coarse intrinsic calcification is present, with cusp tears and frayings, mainly located at the commissures. (A) Left ventricular view. ( B ) Aortic view. (0Roentgenographic analysis confirms the presence of gross calcium deposits.
PB-related Morbidity and Mortality There were 15 PB-related deaths; death was due to endocarditis in 5 patients, to embolic events in 5 , and to low cardiac output at reoperation in 5 . The linearized rate of PB-related deaths was 1.3 k 0.4%/patient-year, and actuarial freedom from PB-related deaths was 88.5 f 3% at 10 years and 66.3 k 19% at 14 years (Fig 7). PB failure developed in 56 patients and was caused by PTF in 40 (71.4%), endocarditis in 7 (12.5%), thromboemboli in 5 (8.9%), and perivalvular leak in 4 (7.2%).The overall linearized rate of PB failure was 4.9 & O.b%/patient-year, and the actuarial freedom was 45.7 f 6.3% at 10 years and 34.3 11%at 14 years (see Fig 7). PB-related complications occurred in 64 patients (5.6 & 0.2%/patientyear): PTF in 40 patients’ events in anticoagulant-related hemorrhages in 2, endocarditis in 7, and perivalvular leak in 7. At 10 and 14 years, respectively, 40 k 6% and 30 k 10% of patients were free from overall PB-related complications (see Fig 7).
*
’’
Comment The Hancock porcine valve has been the PB of choice in our center since 1970 [3,4, 111. We have used this device
220 The Annals of Thoracic Surgery Vol 46 No 2 August 1988
A
C Fig 6 . Gross view of an aortic porcine bioprosthesis explanted after 80 months because of pure, severe regurgitation. The noncorona y cusp shows a large basal tear with loss of substance due to calcific deposits. Tears are also present at the commissure between the right and left coronay cusps, resulting in cusp prolapse. (A) Left ventricular view. (B)Aortic view. (C) The presence of difuse calcification is evident roentgenographically.
B
mainly in the mitral position, and the long-term results after mitral valve replacement have been gratifying in terms of overall valve performance [4]. We have used the Hancock PB in the aortic position in a more limited number of patients, particularly because of its unfavorable hemodynamics in the small sizes, in which important transprosthetic gradients have been occasionally observed [12]. In fact, most of the PBs used in our series had a diameter of 25 or 27 mm, while in patients with a small aortic annulus, we have always preferred to use a mechanical prosthesis with or without an annulus enlarging procedure. Many reports on the clinical durability of the Hancock PB have underlined the advantages, such as low thromboge,nicity, and the drawbacks, such as the limited durability, of this device, but these results are mostly limited to the first postoperative decade [l, 2, 131; therefore, we believe that data on a more extended follow-up may contribute to a better overall assessment of the performance of the standard Hancock PB. In reviewing our experience, we have focused on our entire population of patients who underwent AVR with this PB. In this subset, the actuarial patient survival rate at 10 years approximates 70%, a figure that compares favorably with rates reported by others using mechanical prostheses [6, 141. Previous reports have confirmed the superiority of PBs over mechanical valves with regard to the incidence of thromboembolic or anticoagulant-related complications [6, 14, 151. In our experience, almost 90% of patients are free from emboli at 14 years after AVR. This
221 Milano et al: Long-Term Follow-up of Porcine Valve Recipients
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Fig 7. Actuarial curve showing freedom from bioprosthesis (PB)-related deaths, PB failure, and overall PB-related complications.
confirms previous observations on the low thrombogenicity of the Hancock PB in the aortic position [3, 11, 131, particularly considering that 84% of our patients were not receiving long-term anticoagulation. Therefore, we think it is justified to avoid any long-term anticoagulant treatment for AVR with a Hancock PB. Further reduction of embolic episodes in this patient subset could be obtained by the administration of antiplatelet drugs, as recently reported [16]. Although this treatment was seldom used in the present series, the use of antiplatelet agents might be indicated in patients with chronic atrial fibrillation after AVR. In our experience the majority of thromboembolic events occurred after the fourth postoperative year. Although there was no clear relationship between emboli and PTF, at least part of these late events might be related to embolization of calcific cusp fragments, as previously reported for mitral Hancock PBs [17]. Endocarditis is an uncommon complication of AVR with a PB, but it remains a serious problem since it is associated with a high mortality (66.6% in this series). As previously described, infection of Hancock PBs is usually from a vegetative process that directly involves the cusp tissue, leading to leaflet perforation and incompetence. The frequency of septic embolization and consequent spreading of the infection most likely account for the high operative mortality in these patients [MI. Durability remains the major problem of tissue valves and represents a serious concern for the surgeon. PTF is the leading cause of PB dysfunction, and its morphological substrates have been extensively investigated [5,19]. This process is mainly precipitated by progressive accumulation of calcium deposits within the leaflets, which in aortic PBs causes cusp tears or perforation and com-
missural detachment. Therefore, unlike mitral PBs in which tissue calcification usually results in cusp stiffening and valve stenosis, in our experience incompetence is the predominant mode of failure of aortic PBs [19]. A total of 40 patients have undergone reoperation because of PTF after AVR. Our results indicate that durability of this device is quite acceptable up to 8 years but becomes questionable beyond this time, when the actuarial curve of freedom from PTF drops progressively and reaches figures as low as 40% at 14 years, even though the number of patients at risk at the end of our follow-up period is probably too small for definite conclusions. We have not been able to demonstrate that valve position plays a major role in influencing the structural failure of PBs, since in our experience the probability of being free from PTF is similar for patients with AVR or mitral valve replacement [ll]. Unlike dysfunction of mechanical prostheses, failure of PBs occurs progressively and allows in most cases elective reoperation, which can be performed with acceptable risk [19]. Nevertheless, the mortality observed in this series indicates that reoperation must not be regarded as a trivial problem, particularly as in a few instances sudden onset of failure may require emergency reoperation, which cames a considerably higher risk [20]. In analyzing the long-term results of Hancock PB recipients, we have followed the criteria suggested by the Stanford group [6, 131, believing that the incidence of PB failure and PB-related mortality and morbidity are useful parameters to evaluate the overall performance of this device. In this respect, as the follow-up of PB recipients progresses, it appears evident that the impact of valve failure, mainly due to PTF, on PB performance becomes more important. In fact, while 88% of patients were free from PB-related deaths at 10 years and 66% were free at 14 years, only 45 and 34%, respectively, were free from PB failure at the same intervals. Based on these results, the overall performance of the
222 The Annals of Thoracic Surgery Vol 46 No 2 August 1988
standard Hancock PB after AVR deteriorates considerably after the tenth postoperative year and becomes unsatisfactory when the follow-up approximates 15 years. Therefore, it appears justified to limit the use of this PB to patients above 60 years of age and to peculiar indications such as the occasional female patient who plans a pregnancy [21] or patients who, for social or psychological reasons, appear unlikely to follow an anticoagulation regimen. However, because freedom from PB-related deaths remains high even after the first decade, we are encouraged to offer this PB for AVR also to patients who are willing to accept repeat operations and thus enjoy a life without anticoagulation. The authors express their gratitude to Gian Carlo Pengo and Agostino Leorin for their technical assistance. Supported in part by Grant 86 0140457 from the National Council of Research, Rome, Italy, Target Project Biomedical Technology.
References 1. Cohn LH, Mudge GH, Pratter F, Collins JJ Jr: Five- to eight-year follow-up of patients undergoing porcine heart valve replacement. N Engl J Med 304:258, 1981 2. 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 32127, 1981 3. Gallucci V, Valfre C, Mazzucco A, et al: Heart valve replacement with the Hancock bioprosthesis: a 5-11 year follow-up. In Cohn LH, Gallucci V (eds): Cardiac Bioprostheses. New York, Yorke, 1982, pp 9-24 4. Gallucci V, Bortolotti U, Milano A, et al: Isolated mitral valve replacement with the Hancock bioprosthesis: a 13year appraisal. Ann Thorac Surg 38571, 1984 5. Milano A, Bortolotti U, Talenti E, et al: Calcific degeneration as the main cause of porcine bioprosthetic valve failure. Am J Cardiol 53:1066, 1984 6. Miller DC, Oyer PE, Mitchell RS, et a1 Performance characteristics of the Starr-Edwards model 1260 aortic valve prosthesis beyond ten years. J Thorac Cardiovasc Surg 88: 193, 1984 7. Grunkemeier GL, Starr A: Actuarial analysis of surgical results: rationale and method. Ann Thorac Surg 24404, 1977
8. Grunkemeier GL, Thomas DR, Starr A: Statistical considerations in the analysis and reporting of time-related events. Am J Cardiol39:257, 1977 9. Bortolotti U, Milano A, Valfr6 C, Thiene G: Multifactorial stenosis of a porcine aortic valve. Am Heart J 106:166, 1983 10. Thiene G, Bortolotti U, Talenti E, et al: Dissecting cuspal hematomas: a rare form of porcine bioprosthetic valve dysfunction. Arch Pathol Lab Med 111:964, 1987 11. Gallucci V, Bortolotti U, Milano A, et al: The Hancock porcine valve 15 years later: an analysis of 575 patients. In Bodnar E, Yacoub M (eds): Biologic and Bioprosthetic Valves. New York, Yorke, 1986, pp 91-97 12. Jones EL, Craver JM, Morris DC, et al: Hemodynamic and clinical evaluation of the Hancock xenograft bioprosthesis for aortic valve replacement (with emphasis on management of the small aortic root). J Thorac Cardiovasc Surg 75:300, 1978 13. Oyer PE, Miller DC, Stinson EB, et al: Clinical durability of the Hancock porcine bioprosthetic valve. J Thorac Cardiovasc Surg 805324, 1980 14. Cohn LH, Allred EN, Di Sesa VJ, et al: 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, 1984 15. Perier P, Besson JP, Swanson JS, et al: Comparative evaluation of aortic valve replacement with Starr, Bjork and porcine valve prostheses. Circulation 72:Suppl 2140, 1985 16. David TE, Ho WIC, Christakis G T Thromboembolism in patients with an aortic porcine bioprosthesis. Ann Thorac Surg 40:229, 1985 17. Bortolotti U, Milano A, Thiene G, et al: Evidence of impending embolization of a calcific cusp fragment from a mitral porcine xenograft. Thorac Cardiovasc Surg 30:405, 1982 18. Bortolotti U, Thiene G, Milano A, et al: Pathological study of infective endocarditis on Hancock porcine bioprosthesis. J Thorac Cardiovasc Surg 81:934, 1981 19. Bortolotti U, Milano A, Mazzucco A, et al: Results of reoperation for primary tissue failure of porcine bioprostheses. J Thorac Cardiovasc Surg 90:564, 1985 20, Bortolotti U, Guerra F, Magni A, et al: Emergency reoperation for primary tissue failure of porcine bioprostheses. Am J Cardiol 60:920, 1987 21. Bortolotti U, Milano A, Mazzucco A, et al: Pregnancy in patients with a porcine valve bioprosthesis. Am J Cardiol 501051, 1982
Aldo D. Milano, M.D., Uberto Bortolotti, M.D., Alessandro Mazzucco, M.D., Francisco Guerra, M.D., Giovanni Stellin, M.D., Enrico Talenti, M.D., Gaetano Thiene, M.D., and Vincenzo Gallucci, M.D. ABSTRACT All patients undergoing isolated aortic valve replacement with a standard Hancock porcine bioprosthesis (PB), from 1970 to 1983, were reviewed. There were 196 patients, 162 male and 34 female patients, with a mean age of 48 k 12 years. Operative survivors were followed up from 3 to 15.6 years (mean follow-up, 6.6 f 1.5 years), with a cumulative follow-up of 1,140 patient-years, being 100% complete. Actuarial survival was 51 f 15% at 14 years. Eight patients sustained systemic embolic episodes (0.7 f O.Z%/patient-year);actuarial freedom from emboli is 89.4 f 4.3% at 14 years. Reoperation was performed in 53 patients: in 6 because of endocarditis (0.5 f O.Z%/patientyear), in 7 because of perivalvular leak (0.6 f O.Z%/patientyear), and in 40 because of PB primary tissue failure (3.5k O.S%/patient-year). Actuarial freedom from PB-related deaths, PB failure, and overall PB-related complications at 14 years was 66.3 f 19, 34.3 f 11, and 30 f lo%, respectively. This long-term experience shows that the performance of the Hancock PB appears satisfactory up to 8 years, while it progressively deteriorates beyond 10 years because of the impact of primary tissue failure on valve durability, justifying the restriction of its use in the aortic position in selected patients. Although considerable experience has been accumulated on the implantation of the Hancock porcine bioprosthesis (PB), most of the information available is limited to the first 10 postoperative years [1-4]. The Hancock PB has been used clinically at our institution since the early 1970s [3]; therefore, in the present study we reviewed our 15-year experience with all patients who underwent isolated aortic valve replacement (AVR) to provide data for a more extended follow-up of this device.
Patients and Methods From March, 1970, to December, 1983, a total of 196 patients underwent AVR with the standard, glutaraldeFrom the Departments of Cardiovascular Surgery, Radiology, and Pathology, University of Padova Medical School, Padova, Italy. Accepted for publication Feb 9, 1988. Address reprint requests to Dr. Bortolotti, Istituto di Chirurgia Cardiovascolare, Universiti di Padova, Via Giustiniani, 2, 35128 Padova, Italy.
hyde-processed, flexible-stented Hancock PB (Hancock/ Extracorporeal Laboratories, Anaheim, CA). There were 162 male and 34 female patients, ranging in age from 17 to 70 years (mean age, 48 ? 12 years). Preoperatively, 29 patients were in New York Heart Association (NYHA) Functional Class XI, 149 were in Class 111, and 18 were in Class IV. The following list summarizes the indications for AVR: Rheumatic endocarditis Idiopathic calcific degeneration Myxomatous degeneration Infective endocarditis Congenital malformation Failing prosthesis
34.1% 33.1% 18.3% 7.6% 5.6% 1.3%
Figure 1 shows the distribution of PBs implanted according to size; in most of the patients the diameter of the valves ranged from 23 to 29 mm. Associated surgical procedures were performed in 29 patients (15%),including coronary artery bypass grafts in 10, resection of ascending aorta aneurysm in 11, mitral valvuloplasty in 7, and closure of a ventricular septa1 defect in 1.
n= 196 85
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S I Z E S Fig 1. Distribution of the aortic porcine bioprostheses (PB) implanted according to size.
216 Ann Thorac Surg 46216-222, Aug 1988. Copyright 0 1988 by The Society of Thoracic Surgeons
217 mano et ak Long-Term Follow-up of Porcine Valve Recipients
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Fig 2. Actuarial survival curve following aortic valve replwement with a Hancock bioprosthesis. Numbers on the horizontal axis indicate the number of patients at risk. Operative deaths are not included.
Summary of Postoperative Complications No. of
Event ~
~
%/Patient-
Patients
Year
44
3.8 +- 0.6
8 5 2 40 7 7
0.7 2 0.2 0.4 2 0.2 0.1 2 0.1 3.5 2 0.5 0.6 2 0.2 0.6 2 0.2
~~~
Late mortality Thromboemboli Overall Fatal
Anticoagulation-related hemorrhage Primary tissue failure Endocarditis Perivalvular leak
Surgical Technique and Follow-up All patients were operated on using standard cardiopulmonary bypass, moderate systemic hypothermia, topical cooling with or without coronary perfusion, and after 1977 with cold potassium cardioplegia. PBs were implanted with multiple interrupted sutures reinforced with Teflon subannular pledgets when indicated 13, 41. Orally administered anticoagulation was started usually on the second postoperative day; almost all patients were maintained on coumarin derivatives for only 3 months, unless otherwise decided by the referring cardiologist [3]. Follow-up was performed through direct patient evaluation or through questionnaires during a 6-month intervaliending in December, 1986. Cumulative duration of follow-up is 1,140 patient-years, ranging from 3 to 15.6 years (mean follow-up, 6.6 f 1.5 years) and is 100% complete. Explanted PBs underwent detailed morphological studies as described elsewhere [5].
Bioprosthesis-Related Complications Definitions of major and minor thromboembolic episodes, perivalvular leak, endocarditis, and PI3 primary tissue failure (PTF) in porcine valve recipients have been previously reported [3, 41. Anticoagulant-related hemorrhages were considered as any episode requiring treatment or hospitalization. According to the Stanford criteria [6], PB failure is considered as any of the afqrementioned complications causing death or requiring reoperation. Deaths caused by any of these complications or occurring at reoperation are considered PBrelated. Statistical Analysis Continuous variables are presented as means SD, and categorical variables are expressed as percentages with their 70% confidence limits (CL). Rates of patient survival, event freedom, and incidence of PB-related complications are expressed both by actuarial analysis [7] and by linearized rates as percentage per patient-year [8]. The actuarial curves do not include operative mortality, and values are presented as means SEM. Patients were included in the study until their PB was replaced, they died, or were lost to follow-up. Patients were removed from the study while still alive when their original PB was successfully explanted or when an additional valve replacement was performed.
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Results Patient Survival There were 23 operative deaths, with an overall mortality of 11.7% (9.3-14.6%, 70% CL). The cause of death was cardiac failure in 19 patients, postoperative hemorrhage in 2, cerebral damage in 1, and sepsis in 1. Of the 173 patients discharged from the hospital, 44 died during the follow-up period with a linearized rate of 3.8 O.b%/patient-year. The cause of late death was chronic cardiac failure in 12 patients, cerebral embolism in 5, malignancy in 3, prosthetic endocarditis without reoperation in 1, and chronic renal failure in 1. Nine patients died of low output syndrome at reoperation. Finally, the
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218 The Annals of Thoracic Surgery Vol 46 No 2 August 1988
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Fig 3. Actuarial freedom from thromboembolic events after aortic valve replacement.
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Fig 4. Actuarial freedom from primary tissue failure (PTF) after aortic valve replacement.
the fourth postoperative year. The linearized rate of thromboembolic episodes was 0.7 k 0.2%/patient-year, and the actuarial probability of being free from emboli at 14 years was 89.3 4.3% (Fig 3). Anticoagulant-related hemorrhages occurred in 2 patients (0.1 O.l%/patient-year), both of whom were receiving anticoagulant treatment because of chronic atrial fibrillation. Endocarditis occurred in 7 patients (0.6 t 0.2%/patient-year); reoperation was performed in 6 (0.5 -+ 0.2%/patient-year) of them from 1 to 64 months (mean time, 21.4 9.7 months) after AVR, with 4 deaths (66.6%; 37.8-88.5%, 70% CL). Reoperation for perivalvular leak was performed in 7 patients (0.6 t 0.2%/patient-year) from 1 to 93 months (mean, 19 12 months) after AVR, with no deaths.
*
cause of death could not be determined in 13 patients. Actuarial survival at 14 years was 51 15% (Fig 2). Among the 88 long-term survivors, 52 are currently in NYHA Functional Class I and 36 are in NYHA Functional Class 11; 77 patients are in sinus rhythm, 9 are in atrial fibrillation, and 2 have an endocavitary pacemaker. Eleven patients (12.5%) are receiving orally administered anticoagulants, 3 (3.5%) are receiving only antiplatelet drugs, and 74 (84%)are not anticoagulated.
*
PB-Related Complications The Table summarizes the PB-related complications. Thromboembolic events occurred in 8 patients during the follow-up period. Four of them were in atrial fibrillation, and 2 were on a long-term regimen of anticoagulants. Five patients sustained a fatal cerebral embolism. The majority of thromboembolic episodes occurred after
*
*
*
Incidence of Prima y Tissue Failure Primary tissue failure (PTF) led to reoperation in 40 patients after a mean interval of 6.8 2.3 years (range, 3.2-13.2 years), with a linearized rate of 3.5 0.5%/ patient-year. Overall mortality at reoperation for PTF was 12.5%(7.0-20.0%, 70% CL). Elective reoperation was per-
*
*
219 Milano et al: Long-Term Follow-up of Porcine Valve Recipients
A
B formed in 38 patients, with 3 deaths (7.8%; 3.4-15.8, 70% CL), while 2 patients underwent emergency reoperation, and both died (100%; 39-loo%, 70% CL). Actuarial freedom from MT at 14 years was 40.8 12.7% (Fig 4). PTF was caused mainly by cusp calcification, leading usually to valve regurgitation due to commissural rupture or cusp perforation and tears (Figs 5 , 6). Occasionally, PTF was worsened by fibrous tissue overgrowth and inward bending of the stent posts [9] or by a dissecting intracuspal hematoma [lo].
*
C
Fig 5. Gross view of an aortic Hancock porcine bioprosthesis explanted after 78 months because of marked incompetence. Coarse intrinsic calcification is present, with cusp tears and frayings, mainly located at the commissures. (A) Left ventricular view. ( B ) Aortic view. (0Roentgenographic analysis confirms the presence of gross calcium deposits.
PB-related Morbidity and Mortality There were 15 PB-related deaths; death was due to endocarditis in 5 patients, to embolic events in 5 , and to low cardiac output at reoperation in 5 . The linearized rate of PB-related deaths was 1.3 k 0.4%/patient-year, and actuarial freedom from PB-related deaths was 88.5 f 3% at 10 years and 66.3 k 19% at 14 years (Fig 7). PB failure developed in 56 patients and was caused by PTF in 40 (71.4%), endocarditis in 7 (12.5%), thromboemboli in 5 (8.9%), and perivalvular leak in 4 (7.2%).The overall linearized rate of PB failure was 4.9 & O.b%/patient-year, and the actuarial freedom was 45.7 f 6.3% at 10 years and 34.3 11%at 14 years (see Fig 7). PB-related complications occurred in 64 patients (5.6 & 0.2%/patientyear): PTF in 40 patients’ events in anticoagulant-related hemorrhages in 2, endocarditis in 7, and perivalvular leak in 7. At 10 and 14 years, respectively, 40 k 6% and 30 k 10% of patients were free from overall PB-related complications (see Fig 7).
*
’’
Comment The Hancock porcine valve has been the PB of choice in our center since 1970 [3,4, 111. We have used this device
220 The Annals of Thoracic Surgery Vol 46 No 2 August 1988
A
C Fig 6 . Gross view of an aortic porcine bioprosthesis explanted after 80 months because of pure, severe regurgitation. The noncorona y cusp shows a large basal tear with loss of substance due to calcific deposits. Tears are also present at the commissure between the right and left coronay cusps, resulting in cusp prolapse. (A) Left ventricular view. (B)Aortic view. (C) The presence of difuse calcification is evident roentgenographically.
B
mainly in the mitral position, and the long-term results after mitral valve replacement have been gratifying in terms of overall valve performance [4]. We have used the Hancock PB in the aortic position in a more limited number of patients, particularly because of its unfavorable hemodynamics in the small sizes, in which important transprosthetic gradients have been occasionally observed [12]. In fact, most of the PBs used in our series had a diameter of 25 or 27 mm, while in patients with a small aortic annulus, we have always preferred to use a mechanical prosthesis with or without an annulus enlarging procedure. Many reports on the clinical durability of the Hancock PB have underlined the advantages, such as low thromboge,nicity, and the drawbacks, such as the limited durability, of this device, but these results are mostly limited to the first postoperative decade [l, 2, 131; therefore, we believe that data on a more extended follow-up may contribute to a better overall assessment of the performance of the standard Hancock PB. In reviewing our experience, we have focused on our entire population of patients who underwent AVR with this PB. In this subset, the actuarial patient survival rate at 10 years approximates 70%, a figure that compares favorably with rates reported by others using mechanical prostheses [6, 141. Previous reports have confirmed the superiority of PBs over mechanical valves with regard to the incidence of thromboembolic or anticoagulant-related complications [6, 14, 151. In our experience, almost 90% of patients are free from emboli at 14 years after AVR. This
221 Milano et al: Long-Term Follow-up of Porcine Valve Recipients
100
80 66.3t19
60
40
2o
1
34.3?11
30t10 169
160
155
146
133
117
97
8
5
4
Z
156
147
135
119
101
4Y 52
15
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30
A I70
31
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8
5
4
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171
159
154
Id5
133
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6
5
4
2
1
2
3
4
5
6
7
8
9
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1011 1 2 1 3 1 4 1 5
POSTOP
Fig 7. Actuarial curve showing freedom from bioprosthesis (PB)-related deaths, PB failure, and overall PB-related complications.
confirms previous observations on the low thrombogenicity of the Hancock PB in the aortic position [3, 11, 131, particularly considering that 84% of our patients were not receiving long-term anticoagulation. Therefore, we think it is justified to avoid any long-term anticoagulant treatment for AVR with a Hancock PB. Further reduction of embolic episodes in this patient subset could be obtained by the administration of antiplatelet drugs, as recently reported [16]. Although this treatment was seldom used in the present series, the use of antiplatelet agents might be indicated in patients with chronic atrial fibrillation after AVR. In our experience the majority of thromboembolic events occurred after the fourth postoperative year. Although there was no clear relationship between emboli and PTF, at least part of these late events might be related to embolization of calcific cusp fragments, as previously reported for mitral Hancock PBs [17]. Endocarditis is an uncommon complication of AVR with a PB, but it remains a serious problem since it is associated with a high mortality (66.6% in this series). As previously described, infection of Hancock PBs is usually from a vegetative process that directly involves the cusp tissue, leading to leaflet perforation and incompetence. The frequency of septic embolization and consequent spreading of the infection most likely account for the high operative mortality in these patients [MI. Durability remains the major problem of tissue valves and represents a serious concern for the surgeon. PTF is the leading cause of PB dysfunction, and its morphological substrates have been extensively investigated [5,19]. This process is mainly precipitated by progressive accumulation of calcium deposits within the leaflets, which in aortic PBs causes cusp tears or perforation and com-
missural detachment. Therefore, unlike mitral PBs in which tissue calcification usually results in cusp stiffening and valve stenosis, in our experience incompetence is the predominant mode of failure of aortic PBs [19]. A total of 40 patients have undergone reoperation because of PTF after AVR. Our results indicate that durability of this device is quite acceptable up to 8 years but becomes questionable beyond this time, when the actuarial curve of freedom from PTF drops progressively and reaches figures as low as 40% at 14 years, even though the number of patients at risk at the end of our follow-up period is probably too small for definite conclusions. We have not been able to demonstrate that valve position plays a major role in influencing the structural failure of PBs, since in our experience the probability of being free from PTF is similar for patients with AVR or mitral valve replacement [ll]. Unlike dysfunction of mechanical prostheses, failure of PBs occurs progressively and allows in most cases elective reoperation, which can be performed with acceptable risk [19]. Nevertheless, the mortality observed in this series indicates that reoperation must not be regarded as a trivial problem, particularly as in a few instances sudden onset of failure may require emergency reoperation, which cames a considerably higher risk [20]. In analyzing the long-term results of Hancock PB recipients, we have followed the criteria suggested by the Stanford group [6, 131, believing that the incidence of PB failure and PB-related mortality and morbidity are useful parameters to evaluate the overall performance of this device. In this respect, as the follow-up of PB recipients progresses, it appears evident that the impact of valve failure, mainly due to PTF, on PB performance becomes more important. In fact, while 88% of patients were free from PB-related deaths at 10 years and 66% were free at 14 years, only 45 and 34%, respectively, were free from PB failure at the same intervals. Based on these results, the overall performance of the
222 The Annals of Thoracic Surgery Vol 46 No 2 August 1988
standard Hancock PB after AVR deteriorates considerably after the tenth postoperative year and becomes unsatisfactory when the follow-up approximates 15 years. Therefore, it appears justified to limit the use of this PB to patients above 60 years of age and to peculiar indications such as the occasional female patient who plans a pregnancy [21] or patients who, for social or psychological reasons, appear unlikely to follow an anticoagulation regimen. However, because freedom from PB-related deaths remains high even after the first decade, we are encouraged to offer this PB for AVR also to patients who are willing to accept repeat operations and thus enjoy a life without anticoagulation. The authors express their gratitude to Gian Carlo Pengo and Agostino Leorin for their technical assistance. Supported in part by Grant 86 0140457 from the National Council of Research, Rome, Italy, Target Project Biomedical Technology.
References 1. Cohn LH, Mudge GH, Pratter F, Collins JJ Jr: Five- to eight-year follow-up of patients undergoing porcine heart valve replacement. N Engl J Med 304:258, 1981 2. 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 32127, 1981 3. Gallucci V, Valfre C, Mazzucco A, et al: Heart valve replacement with the Hancock bioprosthesis: a 5-11 year follow-up. In Cohn LH, Gallucci V (eds): Cardiac Bioprostheses. New York, Yorke, 1982, pp 9-24 4. Gallucci V, Bortolotti U, Milano A, et al: Isolated mitral valve replacement with the Hancock bioprosthesis: a 13year appraisal. Ann Thorac Surg 38571, 1984 5. Milano A, Bortolotti U, Talenti E, et al: Calcific degeneration as the main cause of porcine bioprosthetic valve failure. Am J Cardiol 53:1066, 1984 6. Miller DC, Oyer PE, Mitchell RS, et a1 Performance characteristics of the Starr-Edwards model 1260 aortic valve prosthesis beyond ten years. J Thorac Cardiovasc Surg 88: 193, 1984 7. Grunkemeier GL, Starr A: Actuarial analysis of surgical results: rationale and method. Ann Thorac Surg 24404, 1977
8. Grunkemeier GL, Thomas DR, Starr A: Statistical considerations in the analysis and reporting of time-related events. Am J Cardiol39:257, 1977 9. Bortolotti U, Milano A, Valfr6 C, Thiene G: Multifactorial stenosis of a porcine aortic valve. Am Heart J 106:166, 1983 10. Thiene G, Bortolotti U, Talenti E, et al: Dissecting cuspal hematomas: a rare form of porcine bioprosthetic valve dysfunction. Arch Pathol Lab Med 111:964, 1987 11. Gallucci V, Bortolotti U, Milano A, et al: The Hancock porcine valve 15 years later: an analysis of 575 patients. In Bodnar E, Yacoub M (eds): Biologic and Bioprosthetic Valves. New York, Yorke, 1986, pp 91-97 12. Jones EL, Craver JM, Morris DC, et al: Hemodynamic and clinical evaluation of the Hancock xenograft bioprosthesis for aortic valve replacement (with emphasis on management of the small aortic root). J Thorac Cardiovasc Surg 75:300, 1978 13. Oyer PE, Miller DC, Stinson EB, et al: Clinical durability of the Hancock porcine bioprosthetic valve. J Thorac Cardiovasc Surg 805324, 1980 14. Cohn LH, Allred EN, Di Sesa VJ, et al: 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, 1984 15. Perier P, Besson JP, Swanson JS, et al: Comparative evaluation of aortic valve replacement with Starr, Bjork and porcine valve prostheses. Circulation 72:Suppl 2140, 1985 16. David TE, Ho WIC, Christakis G T Thromboembolism in patients with an aortic porcine bioprosthesis. Ann Thorac Surg 40:229, 1985 17. Bortolotti U, Milano A, Thiene G, et al: Evidence of impending embolization of a calcific cusp fragment from a mitral porcine xenograft. Thorac Cardiovasc Surg 30:405, 1982 18. Bortolotti U, Thiene G, Milano A, et al: Pathological study of infective endocarditis on Hancock porcine bioprosthesis. J Thorac Cardiovasc Surg 81:934, 1981 19. Bortolotti U, Milano A, Mazzucco A, et al: Results of reoperation for primary tissue failure of porcine bioprostheses. J Thorac Cardiovasc Surg 90:564, 1985 20, Bortolotti U, Guerra F, Magni A, et al: Emergency reoperation for primary tissue failure of porcine bioprostheses. Am J Cardiol 60:920, 1987 21. Bortolotti U, Milano A, Mazzucco A, et al: Pregnancy in patients with a porcine valve bioprosthesis. Am J Cardiol 501051, 1982