Banking of cryopreserved arterial allografts in Europe: 20 years of operation in the European Homograft Bank (EHB) in Brussels.

Vascular allografts have been used for many years in patients with infection complications and when the patient lacks own autologous venous material. Cryopreservation has permitted the long term storage of these allografts, offering the optimal solution for particular clinical situations. For more than 20 years the European Homograft Bank has prepared, stored in the liquid nitrogen vapour below -130 °C and distributed various types of the quality controlled arterial allografts throughout the European centers and elsewhere. The tissues are prepared according to the existing European, Belgian, Swiss and other EU countries' regulations and standards. This paper gives an overview of this activity since 1991. During this period 1,428 batches of arteries were received from recovery centres within European Union and Switzerland and 3,941 arterial segments were evaluated. 1,250 (32 %) were discarded for morphological findings (58 %), bacteriology (31 %) and other reasons, while 2,685 or 68 % (ascending and descending aorta, arch, aortic bifurcation, iliac and femoral arteries and the non-valved pulmonary bifurcations) were cryopreserved and stored. 2,506 arteries were implanted in 1,600 patients in vascular and cardiac centers in European Union and elsewhere. The most important indications were infections (65 %), critical limb ischemia (15 %) and congenital cardiac malformations (15 %). Some allografts were used for the repair of arterial injury (2 %) or prosthetic graft thrombosis (1.5 %). 10 aortic allografts (0.4 %) were used for tracheal replacement in case of cancer. In 52 cases EHB did not fulfill the surgeon's requests due to shortage of arterial allografts. Collaboration with vascular surgeons in the tissue recovery might improve the number, diversity and quality of vascular allografts. A multicentric study is necessary to evaluate the long-term outcome of these allografts.

European homograft bank: twenty years of cardiovascular tissue banking and collaboration with transplant coordination in Europe.

Established in 1989 in Brussels as an international nonprofit association, the European Homograft Bank (EHB) has been collaborating closely with the transplant coordination of the different centers in Belgium and other European countries. Donor selection is made after discussion of exclusion criteria with the transplant coordinator of the procurement center. EHB collaborates with 15 Belgian, 11 German, 10 French, 10 Swiss, 3 Italian, 3 Dutch, and some other procurement and/or implantation centers. Donor ages range from newborn to 65 years. Tissue preparation, morphologic evaluation, and functional testing are performed under Class A laminar flow. After decontamination in a cocktail of 3 antibiotics (lincomycin, vancomycin, and polymixin B) during 20-48 hours, the tissues cryopreserved with liquid nitrogen to -100 degrees C are stored in vapors of liquid nitrogen below -150 degrees C for a maximum of 5 years. Systematic virologic examination of donor blood is performed for HIV, HTLV, hepatitis B/C, and syphilis, as well as for enteroviruses, Q fever, malaria, and West Nile virus by indication. Bacteriologic examination for anaerobic and aerobic contamination is performed at the different steps of processing. Histologic examination for malignant disease and infection is performed systematically. Indications for implantation are discussed with the requesting surgeon. Transport to the implantation center is carried out safely in a dry shipper at -150 degrees C or in dry ice at -76 degrees C. The EHB received 4,511 hearts and 1,169 batches of arteries from January 1989 to December 2008. The 5,133 heart valves (1,974 aortic, 3,106 pulmonary, and 53 mitral) and 2,066 arterial segments have been prepared and stored; 4,600 cryopreserved valvular (2,717 pulmonary, 1,835 aortic, and 48 mitral) and 1,937 arterial allografts have been distributed for implantation in various European Cardiovascular Centers. EHB is not always able to meet the increased demand for heart valves and arterial allografts. Collaboration between the EHB and the Transplant Coordination is satisfactory. Donor selection criteria are discussed with the transplant coordinator; whereas, implantation indication, with the implanting surgeon. Because the EHB is not always able to meet demands for the cryopreserved valves and arterial segments, there is a need to increase number of procurements. Cardiovascular surgeons need to play more active roles in the resolution of this problem.

Use of cryopreserved arterial homografts for management of infected prosthetic grafts: a multicentric study.

The objective of this study was to evaluate the effectiveness of cryopreserved arterial homografts for management of prosthetic graft infection. Between October 1992 and July 1998, 90 patients (84 men) with a mean age of 64 years from six different hospitals were treated for prosthesis infection by in situ replacement using a cryopreserved arterial homograft (CAH). In 43 patients (47%), the primary procedure had been performed at a nonparticipating center. Prosthetic graft infection occurred early (i.e., within 1 month after the primary procedure) in 15 cases and late in 75 cases. In the late group, the mean interval between the primary procedure and CAH replacement was 34 months (range, 3 to 330 months). In 41 patients, infection was located in the aortic region, including 17 presenting with enteroprosthetic fistula (EPF). In 49 patients, infection was confined to the femoral, popliteal, or subclavian region. Bacteriologic cultures were positive for one or more germs in 75 patients and negative in 15. The surgical procedure consisted of complete or partial removal of the infected prosthetic graft, debridement, and in situ reconstruction using one or more CAH. Our results showed that management of prosthetic graft infection, a grave complication, using a CAH is a promising technique, especially for patients in stable condition prior to reconstruction.

Are pulmonary homografts which were subjected to pulmonary hypertension more appropriate for aortic valve replacement than normal pulmonary homografts? A long-term multicentric echography study.

OBJECTIVE: To compare long-term results of the European Homograft Bank (LHB) cryopreserved pulmonary homograft in left ventricular outflow tract (LVOT) subjected to pulmonary hypertension with those subjected to normal pulmonary pressure. The mid-term study of this material published in 1997 showed different results. METHODS: Statistical analysis is calculated by the Kaplan-Meier survival curves, while differences in prevalence by the Log-Rank test. RESULTS: Follow-up (FU) was available in 69 cases (76.7%): 46 in group 1 and 23 in group 2. Five patients have been excluded from the study because of early homograft explantation (technical problems or early valve incompetence). Fourteen out of 43 cases of group 1 (32. 6%) and seven out of 21 cases of group 2 (33.3%) have been explanted after 2.5-88 months and 7-88 months, respectively. Significant echography changes have been found in 19 of 43 (44.18%) of group 1 and 11 of 21 cases (52.38%) of group 2 during the follow-up. Histology showed essentially wear and tear induced lesions. Mean FU was 36.9 (range, 6-88) and 41.3 months (range, 4-88) for group 1 and 2, respectively. No significant difference in the long-term outcome have been found between the two groups (P=0.38). CONCLUSION: Contrary to our previous echocardiography study of mid-term implants the long-term follow up of the PHGs implanted in the LVOT did not show better function of the pulmonary homografts subjected to pulmonary hypertension than those with normal pulmonary pressure. The high failure rate of the PHGs should discourage their use for LVOT reconstruction. Further echocardiography studies of remaining PHGs implanted in the LVOT, and gross and microscopic explant studies are required to judge on the definitive outcome of these grafts.

Multiple aneurysmal dysplasia of pulmonary valvular sinuses with congenital focal aplasia of the annulus.

We report the case of a 22-year-old woman in whom a focal aplasia of the pulmonary valve annulus associated with a multiple aneurysmal compensatory dysplasia was found. This patient had been followed since the age of seven years for a congenital asymmetric hypertrophic cardiomyopathy. Cardiac Doppler analysis showed significant pulmonary valvular insufficiency. The patient underwent heart transplant surgery because of total and refractory cardiac insufficiency. Pathological examination of the explanted heart (at the European Homograft Bank) enabled us to describe this valvular malformation. To date, this anomaly has not been described in the literature. Whether it is a malformation discovered fortuitously, or whether it is responsible in part for some of the signs associated with congenital hypertrophic cardiomyopathy is unclear. However, its role might be disclosed by a rigorous investigation of the patient's family.

Experience with cryopreserved arterial allografts in the treatment of prosthetic graft infections.

The authors present a retrospective study on 30 patients with prosthetic graft infection. Included are 25 patients with aortic graft infection, three with infection of a femorodistal bypass and two with infected axillofemoral grafts. There were 23 isolated primary prosthetic graft infections and seven aorto-enteric fistulas. Treatment consisted of graft excision and replacement with cryopreserved arterial homografts, harvested from brain-death multi-organ donors. The in situ technique was used in 27 cases. Eight patients died postoperatively and two deaths were from allograft related complications. The operative mortality rate was 11% for isolated aortic graft sepsis and the early limb salvage rate was 100%. Persistent or recurrent infection was noted in two cases. The mean follow-up of the series was 24.5 months and occlusive complications occurred in five patients (23%), which resulted in two major amputations. Serial CT scans showed abnormalities in six of the 22 survivors, all of them related to the aortic segment of the allograft. It is concluded that in situ reconstruction with cryopreserved arterial allografts represents an acceptable alternative, especially in the treatment of isolated aortic graft sepsis. Continued follow-up towards late deterioration and/or occlusive complications remains mandatory.

Aortic root replacement with a pulmonary autograft in young adults: medium-term results in 70 patients.

BACKGROUND: Pulmonary autograft aortic valve replacement has been introduced in our institution in selected adult patients in light of the known disadvantages and limitations of conventional prosthetic valves. METHODS: We prospectively evaluated the use of the pulmonary autograft in a series of 70 young adults (31.2+/-8.7 years, range 16 to 49 years) operated on from March 1992 to April 1997 with aortic root replacement only. RESULTS: There were no in-hospital deaths and two noncardiac-related late deaths during follow-up of up to 62 months (mean 33 months). Thromboembolic complications were not observed. One patient required reoperation for infective endocarditis 4.3 years after surgery. Discharge echo-Doppler studies showed normal autograft and allograft valve function. Serial echo-Doppler studies showed no significant progression of aortic insufficiency and no dilatation of the autograft. A severe stenosis of the pulmonary allograft developed in 1 patient. CONCLUSION: Aortic root replacement with a pulmonary autograft, although more complex than conventional prosthetic valve replacement, is a safe, effective, and reproducible procedure in properly selected adult patients. Long-term results remain to be evaluated.

Are pulmonary homografts subjected to pulmonary hypertension more appropriate for aortic valve replacement than normal pulmonary homografts? Results of echocardiography in a multicentric study.

OBJECTIVE: To compare the function in aortic position of cryopreserved pulmonary homografts subjected to pulmonary hypertension with that of normal cryopreserved pulmonary homografts. METHODS: Pulmonary valves (52) were implanted in aortic position in different cardiothoracic centres. The valves were classified as follows: Group I-pulmonary hypertension (procured from recipients of heart/heart-lung transplantation, 31 valves), Group II-normal pulmonary pressure (procured from cadavers and multiorgan donors, 21 valves). Regular echocardiographic follow-up was obtained by the implanting centers. Significant echo changes were defined as insufficiency > 2+ and/or stenosis producing a delta P > 30 mm Hg. RESULTS: Pulmonary homografts showed the following significant echo changes: in the Pulmonary Hypertension Group, 7, 27 and 33% at 12, 24 and 36 months, respectively; in the normal PA Group 10, 37.5 and 80% at 12, 24 and 36 months, respectively. In both groups the most common echocardiographic alteration was homograft insufficiency rather than stenosis. Thus, pulmonary homografts subjected to long-term pulmonary hypertension have significantly less echo changes than normal pulmonary homografts, especially after 12 months (chi 2: P < 0.036). CONCLUSIONS: These findings suggest that pulmonary valves subjected to pulmonary hypertension might be more appropriate than normal pulmonary homograft for aortic valve replacement, constituting a possible alternative in case of lack of aortic valve homografts. However, the failure of two out of five valves in the longer term must dictate caution while waiting further long-term results.

Eradication of aortic infections with the use of cryopreserved arterial homografts.

BACKGROUND: The surgical treatment of vascular infection is associated with a substantial early and late mortality. Cryopreserved homografts were evaluated for in situ reconstruction in aortic infections. METHODS: Between January 1991 and July 1995, homografts were used in 19 patients (mean age, 61 +/- 13 years; range, 40-85 years) with mycotic aneurysms (9/19; 47%) or infected grafts (10/19; 53%) in the thoracic (7/19; 37%) or abdominal (12/19; 63%) aorta. Sepsis was present preoperatively in 14 of 19 (74%) patients, and 18 of 19 (95%) had received antibiotic treatment for 6.4 +/- 6 months (range, 1-36 months). Up to ten previous vascular procedures had been done in 11 of 19 patients (58%). RESULTS: There was one (5.2%) early and two (11%) late deaths, with one (5.5%) of the late deaths being homograft related. The mean hospital stay was 27 +/- 26 days (range, 7-84 days). Antibiotics were given postoperatively for 30 +/- 12 days (range, 4-84 days). During the follow-up period of 18.6 +/- 13 months (range, 7-60 months), there were no instances of reinfection, suture line rupture, homograft stenosis, or anastomotic aneurysms. CONCLUSIONS: Cryopreserved arterial homografts allow safe in situ reconstruction, decrease early and midterm mortality, and reduce antibiotic requirements. Early and midterm reoperations are unnecessary.

Banking cryopreserved heart valves in Europe: assessment of a 5-year operation in an international tissue bank in Brussels.

OBJECTIVE: The heart valve bank of the European Homograft Bank has been set up in 1988 to meet the growing demand of cardiac surgeons for various sized and quality controlled cryopreserved homografts. METHODS: Heart valve donors less than 60 years of age were classified in 3 categories: multiorgan donors with non transplantable hearts, recipients of cardiac transplantation and non beating heart cadavers with a warm ischemic time of less than 6 hours. Past history and biology were checked for transmissible diseases. Preparation, progressive freezing and storage in liquid nitrogen vapors, and quality control were according to the standards of the Belgian Ministry of Health. RESULTS: From end January 1989 to end May 1994, 989 homograft valves were cryopreserved (514 pulmonary, 475 aortic and 3 mitral) whereas 962 valves were discarded. The first cause of rejection being a major macroscopic lesion (41.48%). 138 hearts accepted at inspection were contaminated and 43 cases remained so after antibiotics. 38 cases were positive for hepatitis B or C. Complication at distribution and thawing included 10 instances of bag rupture and 15 of transversal fracture through the wall of the conduit. 477 aortic, 474 pulmonary valves as well as one mitral were implanted between May 1989 and May 1994, either for left or right ventricular outflow tract reconstruction. In the left ventricular outflow tract series 111 aortic and 23 pulmonary homograft valves were used in cases of native endocarditis, prosthetic endocarditis or recurrent endocarditis after homograft implantation. 9.6% of the requests could no be satisfied. Regular follow up information was available from 382 implants-40.1% only. CONCLUSIONS: The assessment of 5 years operation of the heart valve bank indicates: 1) the efficiency of selecting, cryopreserving and allocating quality controlled homograft valves from a large pool of donor hearts provided by a network of hospitals; 2) the difficulty of obtaining regular follow up information on the implants.

Recurrent aortic infection: treatment by arterial homograft replacement.

Deep infection remains the most problematic complication following prosthetic aortoiliofemoral reconstruction. Prosthetic excision and extra-anatomic revascularization is associated with significant morbidity and mortality. The possibilities of autogenous reconstruction are frequently limited. The authors present a patient with recurrent aortic infection who was successfully treated by prosthetic excision and revascularization in situ with a cryopreserved arterial homograft.

In situ hybridization: a new technique to determine the origin of fibroblasts in cryopreserved aortic homograft valve explants.

Tissue degeneration reduces the durability of cryopreserved homografts. Earlier studies indicated that the presence of fibroblasts in homograft leaflets may contribute to increased valve longevity. These fibroblasts may be of recipient origin or represent surviving donor cells. We developed a method, based on in situ hybridization, to determine the origin of fibroblasts in homograft explants. In young pigs we performed aortic valve replacement with a cryopreserved porcine aortic homograft. A male homograft was implanted in a female pig, whereas two male recipients received a female homograft. After 3 to 4 months the homografts were explanted. Frozen sections were made and alternately examined with hematoxylin-eosin staining and in situ hybridization. With a biotinylated porcine Y chromosome-specific deoxyribonucleic acid probe, male fibroblasts could be clearly distinguished from female fibroblasts. In all leaflets we observed both donor and recipient fibroblasts. The distribution of these populations was marked in schematic drawings. Recipient fibroblasts mostly spread onto the leaflet surface but also penetrated the leaflet tissue. Remaining donor fibroblasts did not show morphologic signs of decreased viability on hematoxylin-eosin staining. In situ hybridization may become a useful technique in homograft research. In this porcine model, the fibroblasts in the aortic homograft explants were of both donor and recipient origin.

Right ventricular outflow reconstruction with homografts.

Ninety children and young adults underwent right ventricular outflow tract (RVOT) reconstruction with aortic or pulmonary homografts from May, 1989 to May, 1994. The patients were divided into three groups according to preoperative diagnosis: RVOT obstructions with ventriculo-arterial (VA) concordance (61), RVOT obstructions with VA discordance (18) and truncus arteriosus (11). Of the reconstructions, 52% were reoperations. A pulmonary homograft was used by preference (85% in the concordant group and 33% in the discordant group). One patient died after homograft correction (hospital mortality 1.1%). The mean follow-up was 32 +/- 22 months. One patient died after 10 months due to congestive heart failure and obstructive pulmonary hypertension. All other patients were in NYHA classes I-II. Three patients (two discordant and one truncus correction) underwent reoperation because of aortic homograft dysfunction and calcification. The incidence of significant (> or = 40 mmHg) gradient across the reconstruction found at the last echocardiographic control was 4% in the concordant, 28% in the discordant, and 18% in the truncus, group. Echocardiographic evidence of moderate (grade 2-3/4) pulmonary regurgitation (PR) was noticed in 24 and 13% of the concordant and discordant groups, respectively. From this medium-term experience it is concluded that (1) the medium-term performance of cryopreserved homografts is excellent, even in young patients, (2) corrections in patients with VA discordance need close follow-up, (3) the use of pulmonary homografts, especially in VA concordant lesions, should be encouraged, (4) longer-term follow-up is necessary to confirm the superiority of the cryopreserved homograft when compared to the porcine xenograft in the RVOT.

Cryopreserved arterial homografts for in situ reconstruction of mycotic aneurysms and prosthetic graft infection.

The management of mycotic aneurysms and prosthetic graft infection of major thoracic and abdominal vessels and infected extra-anatomic bypass remains a problem in vascular surgery. Cryopreserved arterial homografts, being resistant to infection, offer hope for in situ vascular reconstruction in the presence of an infection. We analyzed clinical, microbiological, preoperative and postoperative magnetic resonance imaging (MRI), computed tomography (CT), echocardiography and/or angiography data in 12 patients with mycotic aneurysm or prosthetic graft infection, in whom cryopreserved arterial homografts were used to replace infected segments of major thoracic and abdominal vessels. The hospital mortality was 8.3%. The average postoperative hospital stay was 18 +/- 14.5 days (6 to 45); antibiotic treatment was continued for 31 +/- 12 days (4 to 42). During the mean follow-up time of 18.6 +/- 12.8 months (2 to 48) two patients died, but only one (9%) was homograft-related. Recurrence of infection, suture line problems or homograft stenosis or aneurysm were not observed. Therefore, in situ replacement with cryopreserved arterial homografts is an effective treatment for mycotic aneurysms and graft infection of thoracic aorta, abdominal aortic/iliac vessels and infected extra-anatomic bypass. This operative technique has a low early and late mortality, obviates the need for complex extra-anatomic reconstruction, allows safe in situ repair, reduces postoperative antibiotic requirements, shortens the hospital stay and renders early or medium-term reoperations unnecessary.

The value of the stentless biovalve prosthesis. An experimental study.

Clinical use of the stentless bioprosthesis has not yet been accepted world-wide. Experimental studies are scarce. In a study in growing pigs, 23 aortic valve replacements were performed (7 stented bioprostheses (STB), 10 stentless bioprostheses (SLB) and 6 cryopreserved homografts (CAH)). Valves were studied macroscopically and microscopically after explantation. Five animals died between 1.5 and 4 months after implantation. Two STBs showed extreme calcific degeneration. A third STB animal died suddenly: this STB showed only minimal leaflet calcification. One SLB was stenosed with a large fibrin deposit in one cusp, a second SLB showed slight cusp calcification and three were paracommissural tears in one cusp. In all other animals the valves were explanted after 5 to 6.5 months. All STBs showed severe calcific degeneration. Five SLBs showed mild calcific degeneration, while three others were unaltered after 6 months. All CAHs were free of calcific degeneration, three were perfect, two had a tear in a commisure and another was prolapsed with a fibrin degeneration. The speed and extent of valve degeneration were less than in the STB group. The stentless design is an important contribution which may result in a higher durability of bioprosthetic valves.

Left atrial myxoma associated with systemic AA amyloidosis.

A 76-year-old woman presenting with generalized amyloidosis of the AA-type protein was found to have a left atrial myxoma. Retrospective estimation of the concentration of SAA protein, a serum precursor of AA amyloid, before and after surgical removal of the myxoma, showed that the SAA protein had disappeared after the operation. A common manifestation of myxoma is the development of a severe inflammatory syndrome that sometimes simulates rheumatic fever or bacterial endocarditis. However, to our knowledge, it has never been described in association with amyloidosis. We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis.

Amyloid proteins and amyloidoses: complexity updated.

Amyloid is a beta-pleated fibrillar protein principally constituted of light chains of immunoglobulins (kappa or lambda) in primary or myeloma-associated amyloidosis, of AA proteins in secondary amyloidosis and familial. Mediterranean fever, and of variants of prealbumin - now called transthyretin - in senile amyloidosis and in familial polyneuropathies. Other identified amyloidogenic proteins involve APUD protein derivatives (calcitonin), beta 2 microglobulin in chronic hemodialysis-related amyloidosis and beta protein in Alzheimer disease. After a short review of experimental findings and theories concerning the pathogenesis of amyloid deposition, the clinical aspects of amyloidosis are discussed stressing their great diversity. The diagnostic approach is also examined, with particular emphasis on rectal and kidney biopsy and subcutaneous adipose tissue aspirates. Finally, some comments on the treatment of amyloidosis (role of colchicine and DMSO) are made.

The Ionescu-Shiley pericardial valve: results in 473 patients.

From January 1, 1980, through December 31, 1985, 473 patients underwent valve replacement with an Ionescu-Shiley valve. Overall hospital mortality was 7.8%. Major associated procedures and preoperative New York Heart Association (NYHA) Classes IV and V influenced hospital mortality significantly. The mean follow-up was 2.6 +/- 1.3 years. Late mortality was 5.9%. Overall actuarial survival was 81% at 5 years. A chief cause of reoperation was cusp rupture of a mitral prosthesis in 5 patients (all after aortic and mitral valve replacement). The overall actuarial reoperation-free incidence was 93% at 5 years. Thromboembolic (TB) phenomena occurred at a linear incidence of 1.4 +/- 0.3% per patient-year or an actuarial thromboembolism-free incidence of 92% at 5 years. Univariate and multivariate analyses showed that postoperative NYHA Class, rhythm at follow-up, and anticoagulant therapy significantly influenced the incidence of TE phenomena.

Q fever endocarditis: relapse five years after successful valve replacement for a first unrecognized episode.

A 59-yr-old man presented with mitral endocarditis and negative blood cultures. Antibodies to phase 2 and phase 1 antigens of Coxiella burneti were detected and a diagnosis of Q fever endocarditis was made. Five years earlier, this patient had been successfully treated by aortic valve replacement for a first episode of endocarditis with negative blood cultures. Giemsa and Machiavello stains of the native aortic valve were made retrospectively and showed coccobacilli highly suggestive of Coxiella organisms. It is concluded that the first episode was Q fever endocarditis and that the failure to recognize this aetiology at that time, and the absence of adequate medical therapy, is the cause of the present episode.