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Eur J Cardiothorac Surg 2007;31:851-859. doi:10.1016/j.ejcts.2007.02.009
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Allografts for aortic valve or root replacement: insights from an 18-year single-center prospective follow-up study

Johanna J.M. Takkenberg*, Loes M.A. Klieverik, Jos A. Bekkers, Arie Pieter Kappetein, Jolien W. Roos, Marinus J.C. Eijkemans, Ad J.J.C. Bogers

Departments of Cardio-Thoracic Surgery, Cardiology, and Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands

Received 9 September 2006; received in revised form 5 January 2007; accepted 8 February 2007.

* Corresponding author. Address: Department of Cardio-Thoracic Surgery, Bd563, ErasmusMC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. Tel.: +31 10 4635413; fax: +31 10 4633993. (Email: j.j.m.takkenberg{at}erasmusmc.nl).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
Objective: Whether allografts are the biological valve of choice for AVR in non-elderly patients remains a topic of debate. In this light we analyzed our ongoing prospective allograft AVR cohort and compared allograft durability with other biological aortic valve substitutes. Methods: Between April 1987 and October 2005, 336 patients underwent 346 allograft AVRs (95 subcoronary, 251 root replacement). Patient and perioperative characteristics, cumulative survival, freedom from reoperation, and valve-related events were analyzed. Using microsimulation, for adult patients, age-matched actual freedom from allograft reoperation was compared to porcine and pericardial bioprostheses. Results: Mean age was 45 years (range 1 month to 83 years); 72% were males. Etiology was mainly endocarditis 32% (active 22%), congenital 31%, degenerative 9%, and aneurysm/dissection 12%. Twenty-seven percent underwent prior cardiac surgery. Hospital mortality was 5.5% (N = 19). During follow-up (mean 7.4 years, maximum 18.5 years, 98% complete), 54 patients died; there were 57 valve-related reoperations (3 early technical, 11 non-structural, 39 structural valve deterioration (SVD), 4 endocarditis), 5 cerebrovascular accidents, 1 fatal bleeding, 8 endocarditis. Twelve-year cumulative survival was 71% (SE 3), freedom from reoperation for SVD 77% (SE 4); younger patient age was associated with increased SVD rates. Actual risk of allograft reoperation was comparable to porcine and pericardial bioprostheses in a simulated age-matched population. Conclusions: The use of allografts for AVR is associated with low occurrence rates of most valve-related events, but over time the risk of SVD increases, comparable to stented xenografts. It remains in our institute the preferred valve substitute only for patients with active aortic root endocarditis and for patients in whom anticoagulation should be avoided.

Key Words: Aortic valve replacement • Allografts • Prognosis • Reoperation


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 
There is not yet a perfect aortic valve prosthesis. In particular, in non-elderly patients who have an active lifestyle and a relatively long life expectancy, it can be hard to select the preferred aortic valve substitute. Choosing the optimal prosthesis requires careful weighing of the pros and cons of mechanical and biological valve substitutes for each individual patient, taking into account multiple interrelated factors like the expected lifespan of the patient, the willingness to take warfarin (and accept the associated risks) versus risking a possible reoperation for structural valve failure, major contraindications against warfarin therapy, and patient preference [1].

In our own institution we started using allografts for aortic valve replacement in the late 80s, assuming that their durability would be better compared to xenografts, their hemodynamic profile superior to mechanical prostheses and xenografts, and because they offer (in particular young adult) patients the option to live life to the full without the limitations and threats of anticoagulation that would be required after implantation of a mechanical prosthesis. We systematically and carefully follow patients over time and are now able to make statements about valve performance and patient outcome well into the second decade after operation.

The aim of this study is to assess whether allografts are indeed the biological valve substitute of choice in non-elderly patients. This is done by describing the clinical results of aortic valve and root replacement with allografts in our center's prospective cohort study, and comparing the performance of allografts with stented porcine and pericardial bioprostheses in a simulated age-matched population.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 Appendix A
 References
 
Between April 1987 and October 2005, 336 consecutive patients underwent 346 allograft aortic valve replacement or aortic root replacement procedures at Erasmus University Medical Center. All patients who receive an allograft in our center are enrolled in our ongoing prospective follow-up study [2–4]. Institutional Review Board approval was obtained for this prospective follow-up study; the Institutional Review Board waived informed consent. Preoperative patient characteristics are displayed in Table 1 .


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  		Table 1 Preoperative patient characteristics
 
2.1 Operation
Surgical procedures were performed on cardiopulmonary bypass with moderate hypothermia. Crystalloid cardioplegia and topical cooling were used for myocardial protection. Deep hypothermia and circulatory arrest were used in 35 patients with ascending aorta or arch pathology. Early in our experience the subcoronary technique was used, while since 1998 the root replacement technique has become the technique of choice (Fig. 1 ). Subcoronary allograft implantation was done in 95 patients [5], initially with scalloping of the sinus of Valsalva (N = 32), while later on the non-coronary sinus was preserved (N = 63). Root replacement was performed as a freestanding root with reimplantation of the coronary arteries in 251 patients. Characteristics of implanted allografts are displayed in Table 2 .


Figure 1
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  		Fig. 1. Number of allografts implanted with the subcoronary implantation technique and the root replacement technique by year of operation.

 

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  		Table 2 Allograft characteristics
 
2.2 Follow-up
All patients who receive an allograft at ErasmusMC are followed prospectively by annual telephone interviews and through visits to their cardiologist. Echocardiographic follow-up at ErasmusMC is obtained 6 months postoperative, 1 year postoperative, and thereafter, biennially by means of serial standardized echocardiography [3]. Valve-related complications were defined according to the 1996 guidelines for reporting morbidity and mortality after cardiac valvular operations [6].

The study database was frozen for analysis on December 1, 2005. Follow-up was 98% complete: eight patients were lost to follow-up due to emigration. The mean follow-up duration was 7.4 years (range 0–18.5 years), with a total follow-up of 2545 patient years.

2.3 Statistical methods
Continuous data are presented as means (standard deviation, range), and comparison was done using the unpaired t-test unless the data were not normally distributed (Kolmogorov–Smirnov test); in these instances we used the Mann–Whitney U-test for comparison. Categorical data are presented as proportions, and comparison was done using the Chi-square test or the Fisher exact test, where appropriate. All tests were two-sided, with an {alpha}-level of 0.05. Univariate logistic regression analysis was used to study potential determinants of hospital mortality. Cumulative survival and freedom from reoperation or reintervention were analyzed using the Kaplan–Meier method. The survival of a patient started at the time of aortic valve operation and ended at the time of death (event) or at the last follow-up (censoring). The analysis of allograft survival started at the time of implantation and ended with reoperation (event) or last follow-up or patient death (censoring). The Tyrone–Ware test was used to compare Kaplan–Meier curves between surgical techniques (correcting for the differences in follow-up time between the groups). The Cox proportional hazards model was used for univariate and multivariate analysis of time-related events. Backward-stepwise or forward-stepwise selection of potential predictors was employed, with criteria for entering variables: p < 0.05. Variables that were tested as potential risk factors for hospital and late mortality were: patient age (continuous variable expressed in years), gender, preoperative ventilation support, preoperative abnormal cardiac rhythm (any rhythm other that sinus rhythm), preoperative renal function (creatinin, continuous variable expressed in µmol/l), severe renal disease requiring either dialysis or transplantation, prior cardiac surgery, Marfan disease, ischemic heart disease, heart valve disease etiology, preoperative hypertension, systolic left ventricular function (good vs impaired/moderate/bad), prior cerebrovascular accident (CVA), preoperative NYHA class, emergency of the procedure, operative technique, cardiopulmonary bypass time (continuous variable expressed in minutes), and time period of operation (before 1998 vs after 1998). Factors that were tested as potential risk factors for reoperation for structural valve deterioration (SVD) were: patient age (continuous variable expressed in years), gender, severe renal disease requiring either dialysis or transplantation, prior cardiac surgery, heart valve disease etiology, preoperative hypertension, operative technique, surgical experience (considering the first 10 cases of an individual surgeon as inexperienced), allograft characteristics (including aortic vs pulmonary allograft, size allograft (continuous variable expressed in millimeters), type donor, donor age, donor gender, preservation method, quality code), donor–recipient sex mismatch, and time period of operation (before 1998 vs after 1998). For all analyses mentioned above SPSS 12.0 for Windows statistical software (SPSS, Chicago, Ill.) was used. Using Egret, the incidence of structural valve deterioration requiring reoperation was described by a Weibull curve, which is a generalization of the exponential distribution that accommodates a changing risk over time [7–9]. An age parameter that was based on the observed relationship between patient age and structural valve deterioration was added to the Weibull model, allowing for patient age-specific calculations for structural valve deterioration [10,11]. The age-specific Weibull model was entered into a previously developed microsimulation model [12,13] to allow comparison of age-specific patient lifetime risk of reoperation for allografts, and stented porcine and pericardial bioprostheses [14]. The details of the parameters that were used for the microsimulation calculations of the Carpentier–Edwards (CE) pericardial and CE-Supra-annular valve (SAV) bioprostheses were previously published [14]. For each patient age group and valve type, 10,000 patient lives were simulated; background mortality of the general US population was used.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 Appendix A
 References
 
3.1 Early morbidity and mortality
Perioperative data are displayed for all patients and by implantation technique in Table 3 . Coronary artery bypass grafting for complications related to reimplantation of the coronary arteries was necessary in six root replacement patients, of which two subsequently died. In one patient the left coronary artery button was too small, causing coronary ostium stenosis. Another patient had annular calcifications extending up to the right coronary ostium that was very thin-layered and ruptured after reimplantation. A third patient had an active endocarditis of an aortic bioprosthesis with abscesses, and the oedematous right coronary artery button ruptured after reimplantation. Another two patients experienced right ventricular dysfunction due to kinking of the reimplanted right coronary artery. In one patient the coronary artery buttons were very big, probably causing malperfusion of both the right and left coronary artery.


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  		Table 3 Perioperative data
 
During the procedure 5 patients died, and 14 more patients died during the same hospitalization or within 30 days postoperative (hospital mortality 5.5%). The five operative deaths were caused by persistent massive bleeding in three patients (one with an active endocarditis with abscesses, one with an acute dissection, and one patient who underwent a reoperation for paravalvular leakage of a Bjork–Shiley mechanical valve), left ventricular failure in one patient who presented with acute endocarditis with fistula to the left atrium, and finally one patient with prosthetic aortic valve endocarditis with extensive tissue destruction of the left ventricular outflow tract and proximal ascending aorta with abscesses died during a salvage procedure. Causes of death of the 14 patients who died during the same hospitalization or within 30 days postoperative were registered as cardiac and not valve-related in 10 patients, major intracerebral bleeding in 2 patients, a myocardial infarction caused by a kink in the reimplanted right coronary artery in 1 patient, and an acute endocarditis as a result of a stroke caused by septic emboli in 1 patient. Potential risk factors for increased hospital mortality were older patient age (OR 1.07, 95% CI 1.03–1.11; p < 0.001 (continuous variable expressed in years)); severe renal disease (requiring either dialysis or transplantation (OR 11.2, 95% CI 3.4–37.2; p < 0.001)); longer cardiopulmonary bypass time (OR 1.008, 95% CI 1.004–1.013; p < 0.001 (continuous variable expressed in minutes)); emergent procedure (within 24 h (OR 4.3, 95% CI 1.5–12.0; p = 0.006)); abnormal preoperative cardiac rhythm (OR 2.0, 95% CI 1.2–3.1; p = 0.005); preoperative ventilation support (OR 4.9, 95% CI 1.5–16.2; p = 0.01); NYHA class >II (OR 4.4, 95% CI 1.4–13.5; p = 0.01); active endocarditis (OR 2.8, 95% CI 1.1–7.2; p = 0.04); and preoperative hypertension (OR 2.9, 95% CI 1.1–8.0; p = 0.04).

3.2 Late survival
During follow-up another 54 patients died (2.1%/patient year). Of these patients, 36 died of non-valve-related causes. In two patients the cause of death could not be retrieved. Causes of valve-related death (N = 16) were as follows: nine patients died sudden, unexpected, and unexplained deaths; three patients died due to endocarditis; two patients who had structural allograft valve failure died of heart failure; one patient died after a CVA; and one patient died due to a major bleeding. Overall cumulative survival including early survival was 92.7% at 1 year (95% CI 90–96%), 86% at 5 years (95% CI 82–90%), and 71% at 12 years postoperative (95% CI 65–77%). In Fig. 2 cumulative survival for patients operated with the subcoronary implantation technique and the root replacement technique is displayed separately (Tyrone–Ware test, p = 0.03). Independent predictors of late mortality were older patient age (HR 1.04, 95% CI 1.02–1.06; p < 0.001 (continuous variable expressed in years)); preoperative ventilation support (HR 2.5, 95% CI 0.96–6.36; p = 0.06); preoperative abnormal cardiac rhythm (HR 1.9, 95% CI 1.4–2.8; p < 0.001); and the use of the root replacement technique (HR 2.2, 95% CI 1.2–2.4; p = 0.02).


Figure 2
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  		Fig. 2. Cumulative survival after subcoronary implantation vs root replacement.

 
3.3 Reoperation
Reoperation for allograft-related causes was necessary in 57 patients (2.2%/patient year). Reason for reoperation was structural valve deterioration in 39 patients. Non-structural or technical valve failure required reoperation in 14 patients, and persistent endocarditis in 4 patients. The allograft was replaced by a mechanical valve in 39 patients, an allograft in 10 patients, an autograft in 4 patients, and a stented bioprosthesis in 3 patients. One patient did not require replacement of the allograft: a vegetation was removed from the proximal anastomosis of the allograft 3 weeks after the initial operation for active endocarditis. Reoperative mortality was 1.7% (N = 1). Freedom from reoperation for allograft-related causes was 97% at 1 year (95% CI 95–99%), 92% at 5 years (95% CI 88–95%), and 72% at 12 years (95% CI 64–79%), and worse in the subcoronary compared to root replacement technique group (Tyrone–Ware test, p = 0.02).

3.4 Structural valve deterioration
In 39 patients structural valve deterioration caused by degeneration of the allograft was the reason for replacement of the allograft (1.5%/patient year). This occurred in 21 patients in the SC group (1.9%/patient year) and in 18 patients in the aortic root replacement (ARR) group (1.3%/patient year). Freedom from reoperation for structural valve deterioration (N = 39) was 97% at 5 years (95% CI 95–99) and 77% at 12 years (95% CI 69–85%). This did not differ between the subcoronary compared to the root replacement technique group (Tyrone–Ware test, p = ns). Using univariate Cox regression modeling the following factors were found to be potential predictors of the occurrence of reoperation for SVD: patients who received a same-sex donor valve, valves from male donors, the implantation of larger donor valves, and younger patient age (continuous variable expressed in years). Combining these four factors in a multivariate model proved quite tedious since most of them (with the exception of patient age) are strongly correlated. Therefore, we changed our model building strategy from backward- to forward-stepwise selection and started by entering the only variable that was not strongly correlated, namely patient age. Addition of same-sex donor valve to this model revealed that when corrected for patient age, same-sex donor valve was no longer a significant predictor of SVD occurrence (HR 1.9, p = 0.13) and we took it out. Next, addition of donor sex to the model showed that when corrected for patient age, male donor sex remained a significant predictor of SVD occurrence (HR 3.2, p = 0.03), and we left it in the model. In the last step we added allograft diameter (continuous variable expressed in millimeters) to the model and found that, when corrected for patient age and donor sex, a larger allograft diameter was associated with increased SVD rates (HR 1.16, p = 0.05) and male donor sex was no longer a significant predictor (HR 2.4, p = 0.13). Therefore, in our final model independent predictors of structural valve deterioration requiring reoperation were younger patient age at the time of operation (HR 0.96, 95% CI 0.94–0.98 (age continuous variable expressed in years)) and larger allograft diameter (HR 1.2, 95% CI 1.06–1.40 (diameter continuous variable expressed in millimeters)). In Fig. 3 the observed freedom from reoperation from structural valve deterioration and the Weibull function representing the effect of patient age on freedom from structural valve deterioration are displayed. For example, for a 45-year-old patient, median time to reoperation for structural allograft valve deterioration was 16.5 years. The value of the age-dependent scale ({sigma}) parameter of the Weibull model, fitted to represent allograft SVD, was: {sigma} = e 2.0755 + 0.0197 x age. The shape parameter (ß) was estimated at 2.3856. The results of the Weibull model remained virtually unchanged when patients younger than 16 years or older than 65 years at the time of operation were excluded from the model.


Figure 3
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  		Fig. 3. Observed freedom from reoperation for structural valve deterioration (SVD). Superimposed on this curve is the age-dependent Weibull estimate of age-specific freedom from reoperation for structural valve deterioration for patients aged 25–65 years at the time of operation.

 
3.5 Comparison with other biological valve types
Fig. 4 shows patient age-specific (45–65 years) Weibull estimates of reoperation for structural valve deterioration for allografts, Carpentier–Edwards pericardial bioprostheses, and Carpentier–Edwards-SAV porcine bioprostheses. Fig. 5 shows the microsimulation estimates of the ‘actual’ lifetime risk of structural valve deterioration for male patients aged 35–65 years receiving either an allograft, a stented pericardial valve, or a stented porcine bioprosthesis.


Figure 4
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  		Fig. 4. (a–d) Weibull estimate of age-specific freedom from reoperation for structural valve deterioration of allografts vs CE pericardial vs CE-SAV stented bioprostheses for patients aged 35 (Fig. 4a), 45 (Fig. 4b), 55 (Fig. 4c), and 65 years (Fig. 4d) at the time of operation.

 

Figure 5
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  		Fig. 5. Age-specific microsimulation-based estimates of actual patient lifetime risk of structural valve deterioration requiring reoperation for allografts vs CE pericardial vs CE-SAV stented bioprostheses.

 
3.6 Other valve-related complications
During follow-up there were – besides the fatal CVA that was described above – two non-fatal CVAs, one reversible ischemic neurologic deficit (RIND), and nine transient ischemic attacks (TIAs). The linearized annual occurrence rate (LOR) for thrombo-embolic events was 0.5%/patient year. Besides the four lethal bleeding complications described above, there was another major non-fatal bleeding during follow-up. The LOR for major bleeding was 0.2%/patient year. Besides the four endocarditis complications that required reoperation and the four lethal endocarditis complications, there was one non-fatal endocarditis that was treated with antibiotics. The LOR for endocarditis was 0.35%/patient year. No valve thrombosis or peripheral embolism was observed.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
Appendix A
 References
 
Prosthetic valve selection in non-elderly patients who require aortic valve replacement is currently a hot topic of discussion [15,16]. The new 2006 ACC/AHA guidelines for the management of patients with valvular heart disease only provide general recommendations for prosthetic valve selection in non-elderly patients, stating that ‘a mechanical prosthesis is reasonable for aortic valve replacement (AVR) in patients under 65 years who do not have a contraindication to anticoagulation. A bioprosthesis is reasonable in patients under 65 years of age who elect to receive this valve for lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood that a second AVR may be necessary in the future’ [1]. It is difficult to make an educated choice between these two completely different kinds of complications, and patient preference obviously plays an important role in the process. When a decision is made in favor of a biological valve substitute, the next question pops up: Which one? We hypothesized in the late 80s that allografts would have a superior durability and hemodynamic profile compared to stented bioprostheses in non-elderly patients, but the results presented in this paper show that this hypothesis has to be rejected. What insights can be obtained from our 18-year single-center prospective follow-up cohort of allograft patients? Looking back, the high expectations we had 18 years ago can only be met in part. The results show that although the use of allografts for AVR is associated with low occurrence rates of most valve-related events (in particular endocarditis), over time the risk of reoperation for structural valve deterioration increases, and is comparable to stented xenografts.

4.1 Patient survival
Patient survival in our allograft cohort was comparable to other series that report survival after allograft aortic valve and root replacement [15,17–20]. The impaired survival of patients undergoing allograft root replacement versus the subcoronary implantation technique can be explained by the differences in patient profile (less isolated valve disease, more active endocarditis, and complex root pathology) between the subcoronary implantation technique and the root replacement technique. Survival relative to the general age-matched Dutch population is markedly decreased, for example, a 45-year-old male in the general Dutch population has a 12-year survival of 94%, while after allograft aortic valve or root replacement, this is only 71%. This decreased relative survival has become a well-known phenomenon for patients after aortic valve replacement [21], with the exception of patients who undergo a Ross procedure [22,23]. Whether there is patient selection or a true survival advantage in Ross patients will remain a matter of debate until a randomized trial has been conducted.

4.2 Allograft durability
This study shows that allograft durability is age-dependent in non-elderly patients and comparable to two commonly used stented bioprostheses in age-matched individuals who undergo aortic valve replacement. Freedom from any valve-related reoperation was better using the root replacement technique compared to the subcoronary implantation technique. This is in accordance with the observations in a recent systematic review of the effect of allograft implantation technique on reoperation rate [24]. However, when only reoperation for degenerative structural valve deterioration is studied, reoperation rates are comparable between the two insertion techniques. Younger patient age is associated with increased reoperation rates for structural valve deterioration in this cohort, an observation that is confirmed by several other reports [16,18,19]. The effect of patient age on valve durability is also comparable to CE pericardial and CE-SAV stented bioprostheses, suggesting a common pathway of degeneration. This is in accordance with a recently published study from Cleveland, Ohio, that demonstrated comparable failure rates for allografts and stented bovine pericardial prostheses for patients at all adult ages [16]. Our study adds to this the observation that stented porcine bioprostheses also have a comparable age-related valve failure occurrence. Therefore, we can conclude that durability does not play an important factor in choosing either of these three valve types.

4.3 Patient risk of reoperation
Using microsimulation we demonstrated that the actual patient lifetime risk of structural valve deterioration requiring reoperation is comparable for all three valve types. This risk ranges from approximately 15% for a 65-year-old patient to almost 70% in a 35-year-old patient. These evidence-based estimates of actual patient risk of structural valve failure requiring a reoperation may provide a useful tool for patient counseling, quantifying the risks associated with each therapeutic option. The demonstration simulation model (freeware) can be downloaded from our website (www.cardiothoracicresearch.nl) or requested by e-mail.

Reoperative mortality in our series was remarkably low, less than 2%. Although an allograft reoperation can be quite complicated, our results illustrate that it can be accomplished with a low reoperative mortality risk. Key is to closely monitor the patient over time, particularly in the second decade after operation when the risk of structural failure increases. This allows for careful planning of the reoperation, and avoids emergency reoperative procedures in decompensated patients.

4.4 Other valve-related complications
Although durability of allografts is comparable to the most commonly used stented bioprostheses, the occurrence of other valve-related complications is quite low. In particular, the annual occurrence rate of endocarditis is very low in our cohort, given that 22% of patients who received an allograft had an active endocarditis preoperatively. Also, thrombo-embolic and bleeding event rates are low in comparison to stented bioprostheses. However, this observed difference can at least in part be explained by the patient age difference between the allograft and stented bioprosthesis studies.

4.5 Changes in policy over time
Fig. 1 shows that early on in our experience we mainly used the subcoronary implantation technique while by the mid-90s the root replacement technique became the gold standard in our clinic for implanting an allograft in aortic position. As we reported previously, the subcoronary technique has a learning curve and its use resulted in our clinic in several early technical failures [4]. With the shift in surgical technique and due to the emerging disappointing durability outcomes, a change in patient profile took place: while early on in our series allograft aortic valve or root replacement was done in a broad range of patients that required aortic valve replacement, nowadays the main indication for the use of allografts is active endocarditis. Given its excellent resistance to infection, the allograft is a good solution for patients with active endocarditis, in particular, when the aortic root is involved. Allograft root replacement can also be considered for patients with a (relative) contraindication for anticoagulation and patients with aortic root pathology.

4.6 Limitations
Our study reports results from a single institution with a large proportion of patients with endocarditis and root pathology, and may thus not be applicable to all patients who require aortic valve replacement. We were unable to study allograft mismatch as a potential risk factor for the occurrence of structural valve deterioration since we do not systematically measure the recipient annulus at the time of operation. However, in the early postoperative phase only one patient had a gradient of more than 15 mmHg and, therefore, allograft mismatch appears uncommon in our series. Also, the microsimulation estimates that were used to calculate lifetime risks of structural valve deterioration requiring reoperation were largely based on pooled estimates of valve-related complications from published reports. This may have resulted in overestimates or underestimates of complications and, therefore, may have influenced the calculated lifetime risks. Furthermore, we assumed in the microsimulation analyses that all patients with structural valve deterioration were reoperated, while in real life this may not be the case.

4.7 Conclusions and recommendations
The use of allografts for AVR is associated with low occurrence rates of most valve-related events, but over time the risk of SVD increases, comparable to stented xenografts. Lifetime risk of reoperation is considerable, especially in younger patients. Careful follow-up of patients and early recognition of symptoms and signs of structural valve failure are the key to a successful reoperation. The allograft remains in our institute the preferred valve substitute only for patients with active aortic root endocarditis and for patients in whom anticoagulation should be avoided.


   Appendix A
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
References
 
Conference discussion

Dr P. Kolh (Liege, Belgium): I think you are to be congratulated for a very precise and a very careful analysis. I would like to ask you two questions. The first one is I am not quite sure how you chose to define the other cohort, the cohort that you used for comparison and that included patients with a Carpentier–Edwards valve. Are those patients who were operated at the precise same time in your institution or not? I think it should be precised.

And the second question, if I remember correctly, we saw that the survival for patients with subcoronary replacement was better, although they had more long-term deterioration. Can you explain this a little bit?

Dr Takkenberg: To answer your first question, the Carpentier–Edwards pericardial valves were obtained from the premarket approval trial that was conducted in the 80s. So what we did is we obtained the primary data of that trial and superimposed the data on our data, and for the CE-SAV valve we used 1847 patients from Dr Jamieson's experience in Canada.

To answer your question with regard to survival, it is better in subcoronary patients, and on the other end, the freedom from reoperation is worse in subcoronary patients. I find it hard to compare the subcoronary group in our cohort with the root replacement group in our cohort. They are really different patient populations. If you look at the subcoronary patients, most of them had had isolated valve disease while what we see in our root replacement group, a large proportion has active endocarditis, has aneurysm and dissection, and that mainly explains why the survival is so different in the two groups.

Mr J. Pepper (London, United Kingdom): Do you have any information about the character of the donor that produced the homograft, in particular, the ischemic time and the relationship between the age of the donor and the age of the recipient?

Dr Takkenberg: We have detailed information on the donors, which I did not present right now because of time. When it comes to the age of the donor, in our previous report in the European Journal of Cardiothoracic Surgery, we saw that an older donor age was a risk factor for structural valve deterioration. However, we re-did this analysis, and in the multivariate model it is no longer a risk factor.

Mr Pepper: And the ischemic time before the cryopreservation, which is difficult to control?

Dr Takkenberg: It does not affect structural failure in our series.


   Footnotes
 
\#9734; Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Appendix A
 References
 

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