Long-Term Results Of Homograft Valves In Extracardiac Valved Conduits In Relation To The Method Of Preparation
R de Almeida, R Wyse, M Elliott, M de Leval, J Stark
aneurysm, aorta, bypass surgery, cardiac, cardio-pulmonary, cardiopulmonary bypass, cardiothoracic, carotid, chest, heart, heart-lung machine, medicine, surgery, thoracic, valve, vascular, vessel
R de Almeida, R Wyse, M Elliott, M de Leval, J Stark. Long-Term Results Of Homograft Valves In Extracardiac Valved Conduits In Relation To The Method Of Preparation. The Internet Journal of Thoracic and Cardiovascular Surgery. 1999 Volume 3 Number 1.
Homografts have been used since 1966, for definitive repair of complex congenital cardiac disease 1,2. Since then many authors have reported good results in their studies of long-term results 3, 4, 5, 6, 7, 8, 9. Other reports have suggested that calcification and shrinkage of the grafts, is due to different methods of collection, sterilisation and storage and that the methods influence the long-term durability of the homograft valves in extracardiac conduits 10,11. Matsuki et al 12 suggest also that there is a difference in homografts’ long-term performance, in the aortic position, when they are used before three weeks of storage. At The Hospital for Sick Children, Great Ormond Street, London we started to use “fresh” antibiotic-preserved aortic homografts, as extracardiac conduits, in 1971. Since then, until 1986, we have implanted 176 homografts for a variety of definitive repairs. From this groups we were able to collect data on the method of preparation of 122 homografts.
PATIENTS AND METHODS
Between July 1971 and December 1986, 335 children received an extracardiac conduit (we have excluded from this group the left ventricle-aortic conduits), at he Hospital for Sick Children, London. From this group 176 were homografts and, in a retrospective study, we were able to gather data on the preparation method of 122 homografts. >From this group, 114 were “fresh” antibiotic-preserved aortic homografts, the remainder were frozen. From the group of “fresh” antibiotic-preserved aortic homografts we excluded the early deaths (those until 30 days after the primary surgery) and were left with 96 homograft valves.
Our study will try to relate these 96 homograft valves with the long-term results of the patients. The method used, for preservation, was that of Mr. D.N. Ross and the homograft department at the National Heart Hospital 13, 14, 15.
Valves obtained from routine autopsy material were dissected under socially clean but not sterile conditions as soon as possible. We have excluded the valves from any donor with severe hepatitis or suspected liver disease, AIDS, tuberculosis, venereal disease, primary carcinoma of the heart and all conditions of uncertain aetiology where altered immune competence or viral involvement is suspected or implicated. A blood sample was taken to test the present of HAA antigen, HTLV III, virus and blood grouping. Hartmann’s solution at 4º C was used to keep the aortic homograft moist and to wash it. The heart was discarded expect for the intact aortic valve ring, together with as great an aortic length as possible, 3-4 mm of ventricular muscle, the anterior mitral leaflet and, if possible, 3-4 mm of the coronary arteries.
Six samples were cut from the top of the aorta for bacteriologic screening. The valve ring orifices are measured with obturators, which are graduated at 1mm intervals. The prepared homograft was put into a sterile container and the samples into other containers. The valve is totally submerged in the nutrient antibiotic solution. It was kept in this mixture for 24 hours at room temperature (around 20º C) and then transferred to a refrigerator at 4º C for a mean period of 21 days.
The nutrient/antibiotic mixture comprises:
antibiotic mixture (modified by Yacoub 13).
nutrient medium (Al-Janabi 14).
The antibiotic mixture in 91% of cases was:
Cephaloridine 400 mg
Carbenicillin 10 g
Polimixyn B sulphate 10 vials x 500.000 iu
Neomycin sulphate 2 vials x 500.000 iu
In 6.5 % the cephaloridine was substituted by cefuroxine (also 400 mg) and in 2.5% the dosage of cephaloridine used was 10g. The antibiotics were all dissolved in approximately 100 mls of sterile distilled water and added to the nutrient medium.
The nutrient medium was always:
Medium 199 (x10) 88 ml
New born calf heat inactivated 70 ml
7.5% sodium bicarbonate 50 ml
(this was altered to adjust the prime pH to 7.4)
Sterile distilled water was added to the mixture antibiotic/nutrient to bring the final volume to one litre (to sterilise each valve adequately we needed 250 mls). The fungicide (1 vial of 500.000 iu of Nystatin) is suspended in 200 mls of the mixture immediately prior to use.
The type of operation performed, using the 122 homograft valves is summarised in Table 1.
CTGA - corrected transposition of the great arteries.
* Includes Tetralogy of Fallot and absent pulmonary valve syndrome.
The data analysed was storage method, time between donor’s death and dissection of the homograft, time between the homografts’ dissection and use, donors cause of death, age and sex, age at operation as well as the date of the operation. All these were analysed in relation with the long-term survival of the patient or the obstruction of the graft.
The data obtained from these retrospective analysis was coded and stored on a purpose designed data for subsequent analysis using the Scientific Analaysie Systems and the Statistical Package for Social Science, on the university of London’s mainframe computer.
The homograft donors aged between 1 and 62 years (mean 26,7 years), 88% being below 40 years of age, of these 66,9% came from male donors. The cause of death, of the donors, was accident in 62%, suicide in 19,5% and pathologic in 18,5%.
The interval between death and dissection, of the homografts varied from 0 to 4 days (mean 1.63 days). The interval between dissection and usage of the conduit varied between 10 and 68 days (mean 26,9 days), 65,9% of them were stored for more than 21 days . The mean conduit diameter, at valve level, was 20.3mm (8-30 mm).
The risk factors, meeting e significance level of P<01., for conduit obstruction, were time between dissection and usage of the grafts and date of operation (Table 2). The factors found not to be predictive of obstruction included age at operation, donor age and time between the donor’s death and dissection.
This retrospective study was conducted at The Hospital for Sick Children, London due to our disappointment in the replacement rate of homografts and also the small difference in late survival of patients with homografts and xenografts extracardiac conduits 8.
Although knowing that the best method for collection of homograft valves is under sterile conditions, there are some problems in doing it, making it almost impossible, and with an unreliable degree of sterility. In this case the homograft valves were collected under socially clean but not sterile conditions. The ideal time to so is during the first 24 hours of the donors’ death, but some of our valves were collected days after the event.
The ideal method of sterilisation, and storage, should not, in anyway, alter the structure of the valve and preserve the homograft in a viable state 16. It has been long know that the method of sterilising the homografts has a deleterious effect on the tensile strength of the valve, namely the ethyline oxide 17,18, propriolactone 19 and buffered formalin 20. Apart from these, other agents,, such as gluteraldehyde, will also guarantee the sterility of the valve to the cost of rendering the valve and with a variable effect to the collagen. The most widespread method used nowadays is the antibiotic sterilisation introduced by Barratt-Boyes 21.
Our method is the National Heart Hospital’s, one that has been used by other authors with very good results 22,23.
Freezing and hypothermia seem to be the more logical ways to store the homografts. These methods will permit storage for extended periods of time. The question is for how long can a homograft valve be stored without loosing its reliability? Our experience with frozen homografts is rather small, eight in a group of 122. Nevertheless, it is relevant to point out that Lord Brock 24 had already, in 1968, reported that calcification, that is considered a form of degeneration, was commoner in grafts that had been freeze-dried. According to Angel et al the human valve tissue can be kept viable for 3-4 weeks 25. But why is viability important? The impression is that the viability of homograft valves is important for the long-term freedom from valve complications.
In our study we analysed some points that we considered important for thelong-term survival, free from obstruction,, of the homograft valves. In a previous report from this institution 8, the 10 year survival of patients with homografts and heterografts, was 52 ± 14.8 and 53 ± 16.5% respectively and for freedom from death or conduit obstruction 25 ± 11.3 and 14 ± 9.6. Both the parameters were not statistically significant. Despite the fact that there was statistical significance when the homograft group was studied isolated from the cases in which a Dacron extension was used 26 was decided to analyse the possible importance of the homograft preparation. To the best of our knowledge there is no published data analysing this aspect.
None of the risk factors analysed “per se” had statistical significance but, when we joined them into a group, some of these factors came out with a high significance. As some of the factors can not be changed, like age at and date of operation we were left with all the other factors as variables. Donor age is a factor that can be altered if we decide to disregard all the homograft valves from donors older than 40 years of age.
Different from Radley-Smith 27, who found that the increased time between death and dissection was a factor that adversely affected survival, we found no significance, but it is difficult to compare both groups due to the fact that this report analyses only homograft valves in the subcoronary position. We were left only with the length of storage, which was highly significant, especially considering that in our group we had 65,9% with a 3 week or more length of storage.
Other studies are needed in this subject, homograft valves in right ventricular outflow tract and in subcoronary positions to see if there is any relation to the position or only to the homograft itself and its preparation method.
We conclude that homograft valves have an excellent result, used as extracardiac conduits, when used in the first three weeks of storage.