Ann Thorac Surg 2001;71:1471-1476
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Midterm evaluation of the Tissuemed (Aspire) porcine bioprosthesis: 493 patients, 506 bioprostheses
Ira R.A. Goldsmith, MDa,
Tomasz J. Spyt, FRCS C-Thb,
Maria Boehm, RGNb,
Simon Kendall, FRCS C-Thc,
Michael D. Rosin, FRCSa
a Cardiothoracic Surgical Unit of Walsgrave Hospital, Coventry, United Kingdom
b Cardiothoracic Surgical Unit of Glenfield General Hospital, Leicester, United Kingdom
c Cardiothoracic Surgical Unit of South Cleveland Hospital, Middlesbrough, Cleveland, United Kingdom
Accepted for publication December 13, 2000.
Address reprint requests to Dr Goldsmith, Department of Cardiothoracic Surgery, Walsgrave Hospital, Clifford Bridge Rd, Coventry, CV2 2DX United Kingdom
e-mail: ira{at}iragoldsmith.freeserve.co.uk
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Abstract
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Background. Valve durability has been a major concern with bioprostheses, and the Tissuemed (Aspire) porcine bioprosthesis was designed to provide a solution to structural valve failure. Because bioprostheses tend to fail by 8 years, the aim of our study was to determine its midterm durability and performance.
Methods. We reviewed 506 prostheses that were implanted in 493 patients (287 men; mean age 73 ± 6 years) between 1991 and 1999. Preoperatively 316 (68%) patients were in New York Heart Association class III or IV. There were 417 (85%) aortic, 61 (12%) mitral, 13 (2.6%) aortic and mitral, and two (0.4%) tricuspid procedures. Concomitant procedures were performed in 163 (33%) patients. Follow-up was complete in 488 (98.9%) patients with a total cumulative follow-up of 1,402 patient-years.
Results. The 30-day mortality in this elderly population was 10% (95% confidence interval, 8 to 13), with no early valve-related deaths. Patients’ survival at 8 years was 46% ± 7%. This was influenced by the following factors: (1) the patient’s age, being worse for those 70 years or older (p = 0.005); (2) those in New York Heart Association functional class III and IV (p = 0.004); (3) those in atrial fibrillation before the operation (p = 0.006); (4) those with poor left ventricular function (p = 0.009); and (5) those who had a previous cardiac operation (p = 0.003). Valve-related complications (expressed as percent per patient-year) were thromboembolism at 0.9%/patient-year; major hemorrhage at 1.4%/patient-year; bacterial endocarditis at 0.4%/patient-year; nonstructural dysfunction at 0.2%/patient-year, and reoperation at 0.2%/patient-year. At 8 years, freedom from thromboembolism was 93% ± 7%, major hemorrhage, 90% ± 4%, nonstructural dysfunction, 99% ± 1%, structural valve failure, 100%, and reoperation, 99% ± 1%. At follow-up, 98% of survivors were in New York Heart Association class I or II.
Conclusions. Our study suggests that at 8 years, the Tissuemed (Aspire) porcine bioprosthesis is durable and has satisfactory performance with low complication rates.
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Introduction
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The Tissuemed bioprosthesis (renamed the Aspire porcine bioprosthesis) is a third-generation, low-pressure, fixed porcine bioprosthesis presented in two models, the aortic and mitral, for the respective positions of implantation [1]. The bioprosthesis was designed to provide a solution to premature commissural tears and calcification associated with standard porcine bioprostheses and was first used for implantation in the United Kingdom in 1990. Although standard porcine bioprostheses were first introduced for implantation three decades ago and have been extensively studied for functional performance and valve-related complications [2–4], unpredictable valve failure remains a major concern. The second-generation porcine bioprostheses, introduced later, have provided patients with a good quality of life with low valve-related complications; concern nevertheless continues over long-term valve durability [2, 4–6]. A close look at the standard porcine bioprostheses shows that in systole the cusps buckle at the commissures and hence the cusps are subjected to opening bending stresses at the commissures [5]. Repetitive, cyclical opening bending stresses damages the collagen framework and predisposes the leaflets to premature commissural tears and calcification resulting in valve failure [7, 8]. Oversizing of the valve cusps may be one reason for the observed buckling and consequent bending stresses. This can be avoided by freshly mounting and dilating the harvested porcine valve. Correct functional sizing is thus obtained, and commissural alignment is performed by individually aligning the leaflets. By adopting this technique in the construction of the Tissuemed (Aspire) porcine bioprosthesis, the opening bending stresses at the commissures is avoided. Hence, the bioprosthesis may provide a solution to premature commissural tears and calcification. Early clinical evaluation has shown satisfactory clinical performance up to 5 years [1]. However, biologic valves on average tend to fail by 8 years [2–11]. Hence, a longer-term evaluation of the Tissuemed (Aspire) porcine bioprosthesis is warranted and forms the objective of the present study.
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Patients and methods
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The tertiary referral cardiothoracic units in the United Kingdom that agreed to participate in the present study and that implant the Tissuemed (Aspire) porcine bioprostheses were Walsgrave Hospital, Coventry (303 patients), The Glenfield Hospital, Leicester (142 patients), and South Cleveland Hospital, Middlesbrough (48 patients). For patients admitted to these cardiothoracic surgical units, information for the study was obtained from patient notes to a set protocol and proforma and entered into a computerized database. There are seven cardiac surgeons, all of whom undertake valve operations, and the operative techniques were at the discretion of the individual surgeon. After the operation, antithrombotic therapy was initiated in all patients as soon as oral intake was possible. After aortic valve replacement (AVR), low-dose aspirin (75 mg daily) was commenced in all patients who were in sinus rhythm, and the rest of the patients received warfarin therapy. The efficacy of warfarin therapy was monitored by routine measurement of the international normalized ratio.
Follow-up of the patients was conducted by clinical review, postal questionnaire, or direct telephonic contact with the patients and their general practitioner to a set protocol and proforma. The valve-related events were ascertained, and causes of death were determined from the official death register and general practitioner contact and where possible by review of postmortem reports. Performance of the prosthesis was studied according to the guidelines for reporting morbidity and mortality after cardiac valvular operations [12]. The valve-related complications were defined as thromboembolism, hemorrhage, structural valve deterioration, nonstructural dysfunction, and prosthetic valve endocarditis (PVE). Mortality was defined as death within 30 days of operation or in the same hospital admission as operation, regardless of cause.
Data are expressed as mean (± standard deviation) and median (inter quartile range) as appropriate. The valve-related complications were evaluated in the time-related manner with Kaplan-Meier survival curves and given as percent freedom (standard error). Linearized rates, expressed as percent per patient-year were calculated by dividing the number of events by the total follow-up time in years and multiplied by 100. Events were also assessed by the site of implantation, by patient age groups stratified to those younger than 70 years and 70 years or older, and by sex. Survival was also assessed by the aortic valve lesion, namely, pure aortic stenosis, aortic regurgitation, and mixed aortic lesion (and not mitral valve lesion as numbers were small). A probability of less than 0.05 was considered statistically significant.
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Results
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Patient demographics
A total of 506 Tissuemed (Aspire) porcine bioprostheses were implanted in 493 patients, in 493 operative procedures performed between January 1991 and January 1999. Aortic valve replacement was performed in 417 patients (84.6%), mitral valve replacement (MVR) in 61 patients (12.4%), both aortic and mitral, that is, double valve replacement (DVR) in 13 patients (2.6%), and tricuspid valve replacement in 2 (0.4%) patients. There were 287 men (58%) and 206 women (42%). The mean patient age for the whole cohort was 73 ± 6 years and ranged from 42 to 93 years: the mean age of patients undergoing AVR was 73 ± 7 years; MVR, 71 ± 5 years; and DVR, 73 ± 6 years. Preoperatively, 68% of patients were in New York Heart Association (NYHA) class III or IV (Fig 1). The different aortic valve lesions at the time of operation were aortic stenosis in 269 patients, aortic regurgitation in 49 patients, and both aortic stenosis and regurgitation in 83 patients. Seven percent of patients (n = 33) had undergone a previous cardiac operation. Concomitant surgical procedures, primarily coronary artery bypass grafts, were performed in 33% (n = 163) of patients. Hypothermic crystalloid cardioplegia was used in 94% (n = 458) of the operations for myocardial protection, and blood cardioplegia was used in the remainder.
Follow-up
By the date of census, 488 (98.9%) of the patients had been through follow-up. The total cumulative follow-up was 1,402 patient-years (for AVR, 1,204; MVR, 136; and DVR, 48 patient-years). The mean follow-up period was 46.1 months (range, 1 to 95.6 months).
Mortality
The 30-day early mortality in this elderly cohort of patients, which included 13 operative deaths, was 10% (95% confidence intervals [CI], 8 to 13; Table 1). The 30-day mortality for AVR patients was 8.6% (95% CI, 6 to 12), MVR was 20.6% (95% CI, 11 to 32), and DVR was 15.4% (95% CI, 1 to 4), with no early valve-related deaths. The overall mortality and long-term patient survival (Figs 2, 3; Table 2) was influenced by (1) the patient’s age, being worse in those patients 70 years or older (p = 0.005); (2) those in NYHA functional class III and IV (p < 0.0001); (3) those with atrial fibrillation at the time of operation (p = 0.006); (4) those with poor left ventricular function (p = 0.009); and (5) those who had a previous cardiac operation (p = 0.003). After AVR there was no significant difference in the size of implant and patient’s survival at 8 years (Fig 4). The overall patient survival at 8 years was 45.6% ± 6.8%. The late mortality expressed as a linearized occurrence rate was 3.6% per patient-year.
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Fig 3. Valve position and patients’ survival at 8 years. (AVR = aortic valve replacement; DVR = double valve replacement; MVR = mitral valve replacement.)
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Valve-related mortality
There were 15 late valve-related deaths, of which 4 patients had experienced a thromboembolic event alone. In addition, 2 patients had a thromboembolic event and PVE. Four patients had bleeding events, and 2 patients had both thromboembolic and bleeding events. One patient had both bleeding and PVE, and 2 patients had PVE alone. Two patients died after nonstructural valve dysfunction. The valve-related mortality rate was 1.1% per patient-year (Table 3), and overall freedom from valve-related mortality at 8 years was 92% ± 2.1% (Table 4).
Survival according to valve lesion
Outcome for aortic valve lesions is detailed in Figure 5. Although the overall survival of patients who underwent operation for aortic valve disease was 50% ± 7.5%, the survival was significantly higher for those with pure aortic stenosis as compared with those with pure aortic regurgitation and mixed aortic valve disease (Fig 5, p < 0.002).
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Fig 5. Aortic valve diagnosis and patients’ survival at 8 years. (AR = aortic regurgitation; AS = aortic stenosis.)
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Morbidity
Improvement in patient symptoms
There was a significant impact in the NYHA functional class after the operation (Fig 1). At follow-up, 98% of survivors were in NYHA functional class I or II.
Valve-related complications
The valve-related complications were thromboembolism, anticoagulant-related hemorrhage, bacterial endocarditis, and nonstructural valve dysfunction. The linearized occurrence rate for all valve-related complications was 4.9% per patient-year.
Thromboembolism
There were 28 thromboembolic events, despite the patients being on antithrombotic therapy; of these, 15 (54%) were transient episodes (Table 3). In the total cohort the linearized occurrence rate for all thromboembolic events was 1.9% per patient-year. The rate for major, minor, and fatal thromboembolic events (excluding transient episodes per patient-year) was 0.7% per patient-year for AVR and 2.9% per patient-year for MVR (Table 3), and was significantly higher after MVR (
2 = 5.9; p = 0.01). The overall freedom from all thromboembolic episodes (including transient ones) at 8 years was 83.8% ± 4%; although this was lower for AVR as compared with MVR (81.9% ± 4.8% versus 93.2% ± 4.7%), the difference was not statistically significant (p = 0.7).
There were no episodes of obstructive or nonobstructive valve thrombosis leading to valve failure or fatality noted.
Bleeding events
Forty-two patients reported bleeding events after valve replacement surgery, and 19 required hospital admission (Table 3), of which one was fatal because of an intracranial hemorrhage. All MVR and DVR patients who had bleeding events had been discharged home on warfarin therapy after operation, and 60% (n = 15) of AVR patients who reported a bleeding event after operation had been on warfarin thromboprophylaxis. Major and minor bleeding rates by valve position are given in Table 3, and freedom from such events at 8 years is detailed in Table 4.
At 8 years, freedom from bleeding events was significantly higher for patients on aspirin therapy compared with those on warfarin therapy (86% ± 3% versus 69% ± 9%; p = 0.002). However, at 8 years there was no significant difference in the freedom from thromboembolic events between patients discharged home on either aspirin or warfarin therapy.
Prosthetic valve endocarditis
There were five episodes of PVE, three of which occurred in those patients in whom the prosthesis was inserted for infective endocarditis in the first instance (Table 3). The overall freedom from PVE at 8 years was 98.2% ± 0.9% and freedom from PVE after AVR, MVR, and DVR are given in Table 4.
Nonstructural dysfunction
There were three episodes of nonstructural valve dysfunction, two of which manifested as paravalvular leaks. One episode occurred at the mitral site after MVR, and the second, at the aortic site after DVR. The third episode occurred at the tricuspid site and essentially manifested as tricuspid stenosis caused by impairment of mobility of the valve leaflets because of the retained subvalvular apparatus of the native tricuspid valve. The overall freedom from nonstructural dysfunction at 8 years was 99.1% ± 0.5%, and those after AVR, MVR, and DVR at 8 years are given in Table 4. The nonstructural dysfunction rate was 0.2% per patient-year (Table 3).
Structural valve deterioration
There were no episodes of structural valve deterioration. Hence, freedom from structural valve failure at 8 years was 100%.
Reoperation
There were 3 patients who underwent reoperation, which in 2 patients was performed at the aortic and in 1, at the tricuspid position. Reoperations were undertaken for paravalvular leak (one), prosthetic valve endocarditis (one), and tricuspid stenosis (one). Overall freedom from reoperation at 8 years was 99% ± 0.6%, and those after AVR, MVR, and DVR at 8 years are given in Table 4. The reoperation rate for the whole cohort was 0.2% per patient-year (Table 3).
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Comment
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The present study represents the largest reported multicenter study assessment of the Tissuemed (Aspire) porcine bioprosthesis [1]. The study permits us to draw some perceptions regarding the midterm clinical performance of the Tissuemed (Aspire) porcine bioprosthesis.
In the present study the overall risks of thromboembolic complications with the Tissuemed (Aspire) porcine bioprosthesis were very similar to other series of biologic prostheses [2–6, 9, 10]. However, unlike the other series, long-term freedom from thromboembolic episodes was lower after AVR when compared with MVR. The reason for this was not entirely clear. Most episodes involved the cerebral or carotid arterial system, suggesting that factors other than valve type play a significant role in the risk of thromboembolism. For example, the presence of arterial disease in the aorta or carotid arteries may have been a possible source of emboli, especially as 14 of the 23 episodes noted after AVR were transient ischemic attacks involving the carotid artery territory. Another potential source of microemboli may be from microthrombus deposited on atheromatous plaques in the ascending aorta, which are disturbed by blood flow above the aortic prosthesis [13, 14]. Although isolated incidences of prosthetic valve thrombosis have been reported [15], valve thrombosis was not observed in our study.
The principal advantage of biologic valves is freedom from anticoagulant-related hemorrhage because low-dose aspirin in those patients with aortic biologic implants in sinus rhythm provides adequate thromboprophylaxis [1, 16]. In the present study, most bleeding events occurred in those patients who were on warfarin therapy. Indeed, freedom from bleeding events at 8 years was significantly higher in those patients discharged on aspirin therapy compared with those on warfarin therapy (p = 0.002). Significantly, freedom from thromboembolic events was no different in those patients on aspirin or warfarin thromboprophylaxis.
The main disadvantage of biologic valves has been the incidence of unpredictable structural valve degeneration. Structural deterioration after replacement with biologic valves is a function of time [3, 4, 10, 11], the prosthesis itself [2, 4–8, 15], and the patient’s clinical characteristics [9, 10, 17–20]. Age has been demonstrated to be the predominant risk factor for structural failure of porcine bioprostheses, and biologic valves on average tend to fail at 8 years, particularly in younger patients. In the present study, the average age of patients was older than 70 years, and freedom from structural valve deterioration at 8 years in this population was 100%. Hence, our results are consistent with other studies that have shown a low failure rate of biologic valves in the elderly. Moreover, the Tissuemed (Aspire) porcine bioprosthesis was specifically designed to provide a solution for premature commissural tears and calcification associated with standard porcine bioprostheses [1, 5, 7]. The 100% freedom from valve deterioration at 8 years observed in the present study suggests that correct functional sizing (thereby avoiding opening bending stresses at the commissures) and low-pressure fixation may reduce the incidence of structural valve deterioration. Nevertheless, longer-term evaluation is essential to determine the long-term durability of the Tissuemed (Aspire) porcine bioprosthesis.
In our series, 3 patients required reoperation for valve-related complications, giving a rate of 0.2% per patient-year. One was for tricuspid stenosis, the second for bioprosthetic valve endocarditis at the aortic site, and the third for paraprosthetic leak. All three reoperations were required within 2 years of implantation, after which the freedom from reoperation at 8 years was 99% and compares favorably with other porcine series [21].
The early mortality varies with the reported age groups and valve positions [8]. Age, clinical NYHA functional class, poor left ventricular function, previous cardiac operation, and presence of atrial fibrillation influenced the mortality in our series of elderly patients, especially after MVR. Indeed, MVR was undertaken in a small and highly selected group of very sick patients in whom the valve was deemed nonrepairable. Significantly, there were no early valve-related deaths, although there were 15 late valve-related deaths. After AVR, the size of aortic implant did not influence the overall patients’ survival. The 8-year survival is nevertheless comparable to other series [4, 6, 9, 18, 20]. We have also noticed symptomatic improvement, as 98% of surviving patients were in NYHA functional class I or II at follow-up, which is in keeping with the significant morbidity associated with hemodynamically significant valve disease.
In conclusion, valve-related complications associated with the Tissuemed (Aspire) porcine bioprostheses have remained low, with freedom from reoperation at 8 years being 99%, freedom from nonstructural dysfunction being 99%, and freedom from structural deterioration being 100%. Furthermore, after valve replacement, significant clinical improvement in patient symptoms was observed, and freedom from reoperation in most patients has been a major advantage. Because valve durability of porcine bioprostheses is a major concern, long-term clinical assessment of the bioprosthesis is essential to complete the evaluation of the valve. Nevertheless, present indications are that the Tissuemed (Aspire) porcine bioprosthesis is a safe and reliable heart valve, providing good clinical improvement in patient symptoms after replacement.
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Abstract
Introduction
