Long-term follow-up of viable frozen aortic homografts. A viable homograft valve bank.

There is currently a renewed interest in the use of both fresh and commercially available frozen homograft valves for children and young adults. This has prompted us to review a series of 32 patients who received frozen homograft valves for aortic replacement between 1973 and 1975. The cryogenic technique evolved to include the use of selected antibiotics and equilibrated dimethyl sulfoxide solution to freeze homografts at a rate of 1 degrees C per minute to liquid nitrogen temperatures of -196 degrees C. Histologic sections of experimental frozen valves explanted 6 months postoperatively revealed the presence of viable donor cells, and tissue culture demonstrated the reproductive capacity of cusp fibroblasts. Of the 32 frozen viable homografts implanted in this series, 23 were inserted as free-sewn aortic replacements and nine were premounted on stents before implantation in the aortic position. There were two operative deaths, and three valves failed as a result of the technical problems of mounting in one patient and surgical insertion of a free graft in two patients. Of the 22 patients who remained at long-term risk, 13% with free-sewn grafts and 57% with premounted valves underwent reoperation for valve failure. After 10 years of follow-up, 15 (68%) of these patients, 12 (80%) with free-sewn and three (43%) with premounted valves, are alive with their original valve in place. Actuarial analysis shows that 58% of the 32 valves implanted are functional at the beginning of the eleventh year. There have been six late deaths resulting in an overall actuarial patient survival rate of 79% at 10 years and 69% after 13 years. These clinical results are believed to add support to our current application of the frozen homograft in selected patients.

Twelve-year experience with glutaraldehyde-preserved porcine xenografts.

Three hundred fifty-two patients underwent aortic (AVR) or mitral (MVR) valve replacement with a glutaraldehyde-preserved porcine xenograft from 1970 to 1980. Analysis of this series revealed the following information: hospital mortality, 11.6% (41/352); late mortality, 5.5% per patient-year (60/1,090.7); actuarial 5 year survival rate, 70%; incidence of thromboembolism and hemorrhage, 1.4% per patient-year (15/1,090.7); incidence of spontaneous degeneration, 1.1% per patient-year (12/1,090.7); and transvalvular gradient. AVR 16 mm Hg and MVR 4.6 mm Hg. These results compare favorably with results from other porcine xenograft series and with those reported for prosthetic valves. There is no apparent difference in the type of xenograft used with the exception that spontaneous degeneration occurred less frequently in mitral valves that had not undergone pressure fixation than in those that had. The use of flexible stents improved the ease of valve implantation but did not affect leaflet durability as anticipated. Calcification occurred randomly with no relationship to time of implantation. Reoperation was for spontaneous valve deterioration by calcification or collagen degeneration in 11 cases, paravalvular leak in 13 cases, and implantation of an undersized valve in four cases; there was one reoperation for infection. Results support the continued use of porcine xenografts and suggest that improved manufacturing techniques will reduce the incidence of spontaneous, sterile deterioration, which is the only serious drawback to routine use of the porcine xenograft.

Porcine valves.

To date, the glutaraldehyde porcine aortic valve xenograft has proved a good choice for valve replacement in both the aortic and mitral positions. Late thromboembolisms in the absence of long-term anticoagulation is virtually nonexistent in aortic valve replacement and very low in mitral valve replacement patients without a predisposing history. The hemodynamic performance of the porcine xenograft is adequate and comparable to that of mechanical prostheses. The potential for improved hydrodynamic function, particularly of very small sized valves, is great and already being realized. In spite of over 8 yr of xenograft experience, long-term durability remains the primary concern. Histologic study suggests that these valves undergo progressive postimplantation morphological alteration. However, to date, the incidence of tissue failure is very low. Although detailed reports of long-term valve series are surprisingly few, at present, there is no valve replacement device with a 10-yr experience proven structural integrity and a negligible incidence of valve-related morbidity. It will be 3-4 yr before a significant number of porcine xenograft patients either reach this point or experience valve failure. While this review of the valve literature does not permit a statistical comparison of valve types, we feel that it does allow us to attempt a general projection. On the basis of combined survival and valve-related complication rates, at 4 yr, the porcine xenograft appears to be a better choice than the mechanical prosthesis. Excessive tissue failure during the next 3-4 yr might reverse this opinion. However, even if an increase in valve failure does occur, the advantage of noncatastrophic disfunction and decreased valve-related complications may balance the risk of reoperative morbidity and mortality and continue to favor the porcine exnograft. Thus we could speculate that: (1) The tissue valve would be the valve of choice if (A) durability of 10 yr or more is proven, and valve complications with the xenograft remain as presently reported; (B) the incidence of valve complications with the mechanical prostheses at 10-yr follow-up continues to increase. (2) Mechanical prostheses would be the valves of choice if (A) xenograft valve failure is greater than 20% at 10 yr of follow-up; (B) the incidence of valve complications with the mechanical prostheses remains unchanged. (3) The choice of xenograft versus mechanical prosthesis will remain an open issue if valve failure and related complications with both types of device remain below 20% at 10-yr follow-up...

The Angell-Shiley porcine xenograft.

A 4-year clinical experience with fresh allograft tissue valves prompted a trial of 0.5% buffered glutaraldehyde as a valve fixative and sterilant. Tanned allograft and porcine xenograft valves were inserted into experimental animals, and, beginning in 1970, similar valves were implanted in a series of patients now totaling 312. The clinical results are excellent. The 5-year valve-related mortality is 6% for patients who had mitral valve replacement and 16% for those with aortic valve replacement. To date, the incidence of thromboembolism is 1.3% per patient-year, and valve-related morbidity and mortality for the combined groups is 27.4%. Valve stent design has evolved from symmetrically configured metal to anatomically molded plastic. The maintenance of natural valve configuration has optimized leaflet coaptation and support, decreased tissue stress, and eliminated valve-stent dehiscence and tissue rupture seen in valves deformed to fit symmetrical stents. Stent design, controlled glutaraldehyde solutions, and fixation techniques have improved leaflet flexibility and reduced valve orifice to annulus diameter ratios, thus producing transvalvular gradients comparable to both mechanical and modified orifice tissue valves. To date, tissue failure, observed in only 1.0% (3 of 287) of patients, is the result of calcification (2 patients) and cusp rupture due to incomplete fixation (1 patient).

Section of tissue or prosthetic valve. A five-year prospective, randomized comparison.

After considerable experience, controversy persists between the selection of a tissue or prosthetic valve. In order to provide a nonbiased comparison, we designed a prospective, randomized study in September of 1970. Ninety-nine consecutive patients with isolated primary single valve replacement were randomized to tissue or prosthetic valves. The Tissue Bank supplied homografts which were either mounted for mitral replacement or used as free grafts for patients with small aortic roots. Starr-Edwards clot-covered prostheses were used for comparison. There was an even distribution of patients by age, sex, valve lesion, and New York Heart Classification attesting to the accuracy of the random selection. Anticoagulants were used in 33 patients who had operative or embolic evidence of atrial cloth or else history of thromboembolism. Thirty-five patients have undergone postoperative catheterization. Causes of death and valve failure are presented on an actuarial basis. Death in the Starr-Edwards patient group was sudden or due to fabric wear with subsequent thromboembolism, hemorrhage, or infection. We conclude that the tissue valve is a better choice for valve replacement. While there is no significant functional or hemodynamic apparent difference between the tissue and prosthetic valve, there is improvement in patient morbidity and mortality rate with the use of homografts, particularly in the aortic position. The primary cause of complications in the homograft is tissue deterioration, and this problem has been markedly reduced with advent of glutaraldehyde fixation. No such advance in solving the problem of host incompatability with the prosthesis has been forthcoming.