Although, the mechanical and bioprosthetic valves, of good parameters, availability and easy of implantation, are universally applied as substitutes for failed aortic valve, the usefulness of aortic valve allografts (AVA); natural, viable, unstented human valves, is still considered. The essential technology for their preparation is cryopreservation, which allows for long-term storage. Hemodynamic functions of AVA are like of native valve, they do not produce hemolysis nor thromboembolism. Being markedly resistant for infection, AVA are recommended as the optimal grafts for severe endocarditis. Indeed, there exist some disadvantages, such as low availability, need for a specialized laboratories; implantation may be a challenge. Therefore, AVA are not recommended for routine use. Their important limitation is durability, affected with degenerative processes, characteristic of biological implants. Nevertheless, AVA presented satisfactory clinical results after 10, 20, and more years. This chapter have been discussed in detail the principal issues, connected with AVA, including preparation technologies, indications for use, surgical techniques, and first of all, clinical results.
- aortic valve allografts (AVA)
- preparation technologies
- surgical techniques
- mechanisms of degeneration
- clinical results
1.1 General remarks
Aortic valve diseases are currently the most common heart valvular pathology and indication for even 300 thousand surgeries annually [1, 2, 3]. In our Institution, it connects 75% of valve operations. The introduction of extracorporeal circulation in 1953 by Gibbon  allowed for intensification of research on heart valve substitutes, focused on availability, facility of implantation, durability (freedom from structural degeneration), mechanical parameters (transvalvular gradient, turbulency), event-free survival (thromboembolism, hemolysis), immunogenity, resistance for infection, need for anticoagulation, quality of life, costs [1, 5].
Transplantation is defined as the transposition of vascularised organs, while implantation as the use of tissues or cells. Basics for transplantation, and transfusion of blood or bone marrow, is immunocompatibility, especially of ABO blood groups, which for implantation is not required [6, 7, 8, 9]. Autotransplantation of autograft is carried out within the same individual; while allotransplantation of allograft/homograft, between donor and accipient of the same species; syngenic transplantation of isograft concerns genetically identic individuals; for transgenic procedures are used organs from genetically modified animals; xenotransplantation of xenograft is the use of biomaterials procured from individuals of other species. Mechanical devices, synthetic and metallic materials, etc., are a special group. Transplants may be biovital (organs, auto- allografts) or biostatic (xenografts).
Principles of procurement and transplantation of organs, tissues and cells define legal acts: national, international (directives of EU), and additional regulations. Special preceptions and high-quality requirements connect laboratories and tissue banks [2, 5, 10, 11]. Clinical guidelines, actualized after the current state of knowledge, prepare adequate medical associations and institutions [1, 12].
2. History and remarks
The Odyssey of research and contribution to obtain optimal native aortic valve substitute started in the early 1950s. The experiments of Lam , were followed with the first human implantation of AVA in 1956 by Murray, however into descending aorta . Duran and others worked-out a method of preparation and insertion of stentless aortic valve allografts (AVA) in subcoronary position [15, 16]. In 1962, Ross  and Barratt-Boyes  independently performed such operations in patients. In Poland AVA was implanted as the first attempt in 1974 by Yacoub , and this procedure developed Dziatkowiak, since 1977. Ross in 1969 introduced pulmonary autografts for the replacement of the aortic valve, with good results in non-elderly patients [20, 21, 22]. Pulmonary allografts were implanted in the aortic position, but unsatisfying [15, 23]. For several decades AVA were the most preferable substitutes for aortic valve [9, 10].
Xenografts were introduced in 1965 by Binet . They are constructed using the animal native aortic valve, or tailored, now with pericardium; and mounted as stented or stentless. The use of advanced technologies for tissue preparation and conservation, decellularisation, anticalcification, resulted with better clinical course and prolonged durability, however degeneration is highlighted [2, 3, 15, 25, 26, 27, 28, 29, 30]. A fancy construction of open-work thermoplastic stent allows for crimp after cooling, and insertion as sutureless, or with catheter techniques: transarterially or transapically (TAVR). These methods are profitable for older and high-risk patients [1, 2, 31, 32, 33]. The first mechanical valve inserted in 1952 Hufnagel into descending aorta , but orthotopically in 1960, Harken , and Starr . The initial high-gradient, lateral flow, heterogenic and thrombogenic constructions were replaced with central flow tilting-disc, and at least with durable, bileaflet valves of near 90° opening angle, low gradient, reduced turbulences, low noisy, and of very good course. The structures being in touch with blood are performed with biologically neutral pyrolytic carbon, however life-long anticoagulation with vitamin K antagonists still remains obligatory [5, 37]. In addition, artificial valves and most xenografts, present discrete motion of whole their body during the cardiac cycle, it may facilitate the formation of perivalvular clefts in endocarditis. On the contrary, only leaflets of AVA are moving, while the remaining parts are firmly connected with the patient’s tissues and pushed to the aorta by the lateral blood pressure.
3. Preparation of allografts
The grafts: aortic and pulmonary valves, and pericardium, are obtained during forensic autopsies, or transplantation procedures (from multiorgan donors, if the heart is not suitable, and from accipients’ hearts). Accepted are donors aged <50 years, after sudden death (stroke, accident, suicide, crime). Excluded are unknown cadavers, persons affected with neoplasia, diabetes, chronic, systemic, degenerative diseases, treated with transfusions or transplantations, infected, intoxicated, irradiated and of high risk (drug additives, tattooed, homosexuals, prostitutes). The prolonged warm ischemia markedly increases tissue injury , therefore we accept delay no longer than 10 hours, also the transport time in cool saline should be limited.
3.2 Laboratory and bank
For grafts’ preparation serve zones of high standards of aseptics and sterility, having boxes-laminars with the flow of filtered air. Staff should be dressed in sterile whole body coverals, gloves, masks and face shields. A separate cryogenic hall, is equipped with refrigerators, freezers and tanks with installations for liquid nitrogen, where the grafts are stored (Figure 1).
All specimens are strictly controlled, especially the valve competency, and measured. The prepared aortic graft contains an aortic valve, ascending aorta, anterior mitral leaflet and some left ventricular muscle. Donor’s samples are taken for histologic, bacteriologic, mycologic, tuberculotic and virologic control. The microbiologic tests are repeated on the next steps of preparation. Serologic examinations include estimation of blood groups, as well as luetic, HIV, hepatitis, cytomegalia tests. Grafts presented any kind of pathology or positive serologic tests are rejected.
All specimens, obtained during transplantation procedures are steril, while the cadaveric, although taken aseptically, may be infected. Therefore, all grafts underwent decontamination in antibiotic cocktails with the addition of Parker’s solution and calf serum, at +4°C. Such technology, implemented in the 1950s for arterial grafts, and since 1968 by Barratt-Boyes, Yacoub, and others for AVA, occurred optimal [11, 27, 38, 39, 43, 44, 45]. As a rule, must be simultaneously used both wide spectrum antibacterial and antimycotic antibiotics, for decrease the bioburden [38, 39]. Their composition will be changed from time to time, according to the actual most widespread bacterial species.
Initially, AVA were stored as „fresh” in a buffered nutrient medium with antibiotics, at +4°C for about one month; they should be used within this time. Cryopreserved AVA, dived in RPMI 1640 medium with the addition of 10% dimethylsulfoxide (DMSO) as a cryoprotectant, are closed in sterile plastic bags, fractionally freezed to −80°C, and then preserved in vapors of liquid nitrogen even for years, at the temperature under −170°C.
Initially used for cornea preservation, was applied for AVA in the early 1970s by Angell and others [34, 44, 46]. There are emphasized: long-term valve banking with full-size range availability, great potential of patient/donor matching, possibility of use of all prepared tissues, improved sterility, rare iatrogenic infections . The slow cooling of 1°C/min. is strongly recommended, because rapid processing is harmful for viable cells . Freezing is supported with cryoprotectants, such as ethylenglycol, glycerol, polyvinylpyrolidine, and mostly DMSO. Their role consists in the reduction of cooling injury, such as ice formation, membrane fusions, damage of endothelial cytosolic and mitochondrial functions [39, 46]. Endothelium, playing role in the control of hemostasis, coagulation, immunologic and inflammatory responses, vascular tone, may influence the graft function [40, 47]. Meanwhile, own study on AVA (fresh, 1–14 days after procurement, and deep-frozen, stored for 1–15 years), showed massive endothelial decellularisation, which may occur early posthumously . It was mentioned in other papers, however some presented over 70% cell activity [40, 47, 48, 49]. Deendothelialisation corresponds with results of ELISA immunoenzymatic tests, presenting favorable low proteins concentration; no cell activity nor inflammation . The wasted cells are further replaced with neoendothelium. Cellular biology of frozen AVA was described at large [39, 46, 48, 49]. The viability of AVA is recognized as a factor, highly influencing the long-term durability, and evidenced as superior over non-viable tissues [44, 47]. Its estimation consists of the detection of living fibroblasts, culture of them and assessment of glucose utilization [44, 47, 48]. Cryopreservation maintains AVA viability, comparable to fresh grafts [38, 39, 44, 46], and is considered as superior over chemical methods, irradiation and decellularisation [39, 44]. Recryopreservation of AVA is not recommended .
Decellularisation is used between technologies for xenografts’ making. The idea is to remove cells, with detergents or enzymes, to eliminate immunologic reactions. Since 2001, Elkins used this method for AVA . The experimental and clinical experience seems to be promising [28, 29, 40, 51]. Reduction of implant cellularity may enable recellularisation of the matrix with its own cells [28, 39].
3.8 Structural aspects of the stored AVA
Grafts prepared in our laboratory were macroscopically and physically normal. Digital and scanning microscopy showed in general normal leaflets and collagen. However, appeared small (<40 μm) local alterations, as grains, solitary or in chains; gaps among collagen layers, separations and cracks, considered as results of the freezing process [39, 40, 42]. The X-ray spectroscopy did not detect mineralization, except solitary focus. These data support the adequacy of donors’ selection and graft preparation . It has been suggested, that fresh wet storage of AVA may accelerate calcification . Decellularized heart valves, frozen without protection, presented porosity of histoarchitecture, altering biomechanics; sucrose reduced or diminished its formation .
Cryopreserved AVA are rewarming with saline baths of growing temperature; moreover, by stepwise dilution is rinsed the cryopreservant, to stop its potential toxicity. The whole procedure needs at least 30 minutes. In this time may be completed the removal of the native valve and additional procedures. Rapid thawing is preferred, as it restricts ice recrystallization. At the first step AVA is rewarmed to −100°C, and next to +40°C. A slower heating rate would tend to minimize osmotic imbalances, providing for the rehydrating solvent to enter the cells. The rewarming rate, may influence the formation of fissures and cracks . The basal lamina, exposed because of deendothelialisation, suffers destruction: greater occurred during processing in the water bath at 37°C, than in room temperature of 23°C . The last procedure may not be accepted during surgery, because needs about 3 hours.
4. Immunologic issues
Still remain different opinions about the influence of immunologic reactions on AVA deterioration and durability [6, 39, 54, 55, 56]. Even after implantation of the mechanical valve, the myocardial antibodies are released to circulation during surgical manoeuvers. The reaction on residual AVA myocardium leads to local fibrosis. In contrary to endothelial cells, fibroblasts induced only limited proliferation of blood mononuclear and CD4 + T cells . Clarke and others considered that immunologic responses, stimulated by HLA antibodies, cause AVA failure, particularly in young persons [39, 56, 58]. Meanwhile, they have been demonstrated in general locally, as playing not important role in graft degeneration [6, 21, 39, 54]. Cryopreservation, decellularisation, and antibiotic treatment, allow for a significant reduction in immunogenity [28, 30, 39, 54, 56]. The endothelial loss eliminates an abundant source of antigens, while neoendothelium, as own patient’s tissue, is neutral. Usually, AVA are implanted without ABO-HLA matching [8, 30, 39]. Kadner emphasized that it is not necessary, since the absence of valvular endothelial antigens, and suggested, that incompatibility is not responsible for AVA degeneration . This opinion supported Yacoub and Bodnar [6, 54, 59]. On the contrary, Yankah and others, considered blood groups discrepancy as an important risk factor of graft deterioration, and suggested match tests for prevention [49, 55, 58, 60]. In our Institution, AVA are selected by their size (it allows to augment the amount of AVA for implantation); ABO compatibility is present in 30%.
5. Indications for AVA implantation
AVA are used for the treatment of aortic valve and root pathology, as endocarditis, acquired and congenital malformations, aortic aneurysms (also dissected), and for women in childbearing age, patients of contraindications for anticoagulation, or on special request. Limitations, result from availability, need for specialized laboratory, difficult implantation and some medical causes [7, 10, 21, 61, 62, 63]. AVA are rarely applied; in USA their implantation rate dropped to 0.2%, only . The European guidelines do not mention the terms allograft or homograft, while only bioprosthetic valve . Nevertheless, the recommendations for xenografts’ use could be recognized as referred also for AVA. The guidelines of American societies devote attention on AVA, focused on endocarditis, annular destruction, elevated risk of reinfection, reoperative aortic root surgery in patients for whom other techniques will be unfavorable. They do not recommend AVA for routine use, and suggest rather xenografts . AVA durability depends to the patients’ age at implantation, thus may be recommend for patients >60 years, and should not be denied in octogenarians [64, 65, 66], but, in contrary, AVA should not be used in persons with intensive turnover or dysregulations of mineral metabolism, as youngsters or chronically hemodialysed [3, 67]. Endocarditis is a tremendous, often life-treating disease, associated with severe tissue damage. Introduced in 1965 by Wallace ; its surgical treatment is performed often in emergency mode. Radical removal of the native or prosthetic valve and necrotic tissues, supported with intensive antibiotic therapy and local disinfection, is inarguable [62, 69, 70, 71], but it does not exist consensus for the choice of valve substitute. Mostly are used, widely accessible and easy to implant, mechanical or bioprosthetic valves [69, 72, 73], while a large literature expresses excellent opinions on AVA, presented better resistance for infection and transparency for antibiotics [6, 62, 69, 70, 71, 74, 75, 76]. Eventual AVA infection, often curable, develops gradually. AVA may be the only solution, for recurrent prosthetic infections with the perivalvular leak, annular damage, abscess, and/or intracardiac fistula.
6. Techniques for AVA implantation
They have been described and commented in many publications [5, 6, 7, 16, 17, 18, 19, 63, 77, 78, 79, 80, 81, 82]. For access is used median longitudinal sternotomy and anterior aortotomy, leading towards the noncoronary sinus. Extracorporeal circulation, moderate hypothermia and cardioplegia are applied. AVA is a free-hand, flexible graft, which imposes particular conditions towards the surgeon. The main methods for AVA implantation are presented as follows, and in Figures 2 and 3: A. In the Barratt-Boyes technique , all sinuses of Valsalva are excised. The graft is rotated 120° counterclockwise, so that the AVA right sinus lies below the patient’s left coronary sinus, to bring the weaker muscular portion of AVA adjacent to the fibrous trigone and anterior mitral leaflet, while there is not evident its necessity . The annular suture line may be performed with single or continuous sutures. The upper continuous suture mounts the AVA aortic tissue to the patient’s aorta. B. The Ross method  differs from trimming only the coronary sinuses. This may increase the stability of implanted AVA and maintain symmetry more easily, allows for some aortic corrections, reinforcement of aortic suture line, and extent the aortic incision nearly to the annulus. AVA is placed without rotation, and usually with interrupted sutures. Since 2007, I only used the running suture. C. Inclusive short cylinder embraces implantation of the intact aortic bulb with replacement of coronary ostia. It makes easier preservation of geometry and sinotubular junction; is advantageous for endocarditis. We suggest the graft fixation with some mattress sutures, knotted outside the aorta . D. Aortic root technique includes total replacement of the aortic valve and ascending aorta with anastomoses of coronary ostia after the “button” method. We introduced the use of nonexpandable plastic tapes, inserted into the proximal suture line; it allows diminish the enlarged annulus, avoid bleeding and prevent lateannular ectasia in Marfan’s syndrome [19, 63]. E. AVA premounted on a stent did not provide satisfactory results . During operations for degenerated AVA, are used different methods and prostheses. It has been proposed valve-in-valve surgery with excision of AVA leaflets only. As compared with total graft excision, this technique is easier and allows for shortening the duration of extracorporeal bypass and aorta cross-clamping even twice; as well as reducing morbidity and mortality . TAVR is in parallel recommended in selected cases [83, 84].
Some general principles should be respected: a. gentle manipulate, avoid contact of instruments with the leaflets; b. radically remove pathologic tissues, materials, calcifications, debris; c. adequately size; it is recommended AVA diameter 2–3 mm less than the native ostium to prevent graft’s deformation or distension; d. trim the graft appropriately to the choosen implantation method, remove the exceeding tissues, paying attention to the thin spots. An approximately 3 mm wide tissue cuff surrounding the aortic annulus as well as 4–5 mm tissue margin of the aorta for subcoronary techniques should be left for sewing; e. preserve ostium/graft geometry. If AVA is used in patients with the native bicuspid aortic valves, new anatomy should be carefully created, paying attention to coronary ostia. Such surgery is often renounced, but in our Institution connects 25–30% of patients; f. place the commissures optimally to retain semilunar function and valve competency; symmetry and equidistant; g. avoid deformations and torsion; h. preserve sino-tubular junction; i. there may be used single or continuous sutures for mounting the AVA, usually 4/0 (if necessary 3/0 or 2/0); and 5/0 for coronary anastomoses; upper suture line is carried out with continuous suture; j. insert the needle oblique into the grafts’ subvalvular tissue to encompress more material; k. avoid taking the leaflets into the suture line; l. place the sutures more superficially near the membranaceous septum, to escape injury of the conductive tissue; m. if occur a great distance between the graft and coronary ostia during root replacement, an additional vascular prosthesis should be implanted to anastomose them; n. directly control the graft and its competence during surgery, and with transesophageal echocardiography after setting the heart in motion.
7. Postoperative management
Early postoperative therapy is based on general principles of hospital management, including postoperative intensive care. It is similar to the treatment of patients after other aortic valve surgeries, and is focused on parameters connected with cardiac and AVA functions, as well as management of accompanying diseases. We focus on rehabilitation, initiated in the clinic and continued in resort hospital, and for out-patients. It should be introduced secondary prevention with reduction of factors, potentially under the influence of the AVA durability, as hypertension, diabetes, endocarditis, recurrent common infections, etc. Patients should be systematically controlled clinically, and with transthoracic echocardiography (if necessary, also transesophageal). Classical anticoagulation is not required. [6, 7, 8, 9, 21].
8.1 Degeneration and mineralization
The fate of bioprosthetic valves is defined by their degeneration. Its development is usually time-extended, attends to the graft (material, methods of preparation, viability, correctness of implantation, tissue fatigue), patient (age, actual and at operation, history of rheumatic disease, infections, presence of immunologic complexes, genetics, diabetes, arterial hypertension, atherosclerosis, metabolic and hormonal function, renal insufficiency, aortic root distension, diseases of connective tissue, the influence of drugs and their effectiveness), environmental factors, etc. [3, 6, 46, 47, 55, 67, 78, 85, 86]. An advanced phase of biologic valves degeneration is mineralization, interrelated with calcium phosphates It starts in the cytosol and extracellular matrix, where occur centers of mineralization, as “hole zones” in the structure of collagen, areas of damage of collagen and elastin fibers, apoptotic cells, fibrinogen debris; where may be bound ions and substances. Cell membranes and organelles are rich sources of calcium and phosphates. Iron from damaged erythrocytes induces oxidative stress. For mineralization are responsible alterations in collagen synthesis, serum proteolytic enzymes, kinases, calcium binding proteins, increased mineral turnover, hyperparathyreoidismus, etc. Fibroblasts may change their phenotype to osteoblasts. Penetration of immunoactive cells, focal hemorrhages, associated with loss of endothelial integrity worse the anatomy and function of leaflets. Secret mineralization may be identified in explanted tissue samples using diffractometry, spectrophotometry, electron microprobe. Echocardiography detects the advanced lesions.
The visible mineralization contains calcium phosphates and calcium-cholesterol concretions, as grains, multiform accumulations, frequently massive, highly affecting the valve function [3, 42, 51, 52, 67, 85, 86, 87, 88]. In contrary to the native valves, mineralization of AVA embraces mostly areas of sutures, aortic wall, while the distal rims of leaflets may remain free from visible lesions ; Figure 2. The use of running sutures on the annular level, allows for a significant reduction of local calcification.
8.2 Clinical results
8.2.1 Functional status
For an accurate valuation of clinical results have been proposed the following criteria: absence of symptoms and signs of cardiac failure or need for antifailure treatment, no aortic diastolic murmur, normal blood pressure, reduction of cardiothoracic ratio, a decrease of electrocardiographic signs of left ventricular hypertrophy . The literature defines the age of AVA recipients at 7–84, in average 50 years [65, 76, 77, 81, 82, 83, 84], and prevalence of male patients at >70% [68, 69, 82, 83, 89, 90, 91]. In general, postoperatively is observed significant clinical improvement, manifested with the change of NYHA class from III/IV to I/II in 90–98% of cases [7, 41, 77, 79, 81, 92, 93]. Early echocardiographic examinations presented 0/I aortic incompetency in 90–97% of patients, and also low gradient, comparable to physiological [7, 77, 91, 92, 93, 94]. Trivial AVA incompetency seems to be more common after subcoronary than cylinder technique. The parameters of left ventricular anatomy and performance occur significantly improved, but not markedly different from observed after implantation of other prostheses . Generally, is declared improvement of quality of life [93, 95].
Professional or educational activity increased to 67%, as compared with 38% after mechanical valve implantation . Sexual activity improved in 8.6% only, unchanged was in one half of polled, or decreased in the remaining, mostly according to fear. Anxiety reactions complained about 30% of examined patients, and were related with the probability of AVA degeneration or reoperation inspite of over 95% acceptance of this graft. Therefore, patients with the mechanical valve, referred fear towards possibility of thromboembolism or bleeding. Fear was noted also when occurred arrhythmia  Inspite of no anticoagulation, thromboembolism was not observed or extremely rare, because of antithrombotic AVA surface [9, 76, 91, 92, 95, 96]. The development of severe AVA degeneration, parallelly deteriorates the clinical and echocardiographic parameters.
8.2.2 In-hospital mortality
Early mortality after elective fresh [9, 10, 44, 81, 90] and cryopreserved AVA implantation [7, 41, 44, 61, 65, 67, 68, 77, 79, 95] was similar, and varied between 1.5-9.5%, mostly about 5%. After aortic root replacement was referred to 3–11.6%, mostly 7%, for elective surgery, but was elevated up to 24%, while urgent mode for aortic dissection or prosthesis replacement [10, 75, 78, 82, 91, 92]. Redo surgery was connected with mortality of about 7–9% [84, 94, 97, 98]. Risk of AVA implantation for endocarditis of aortic valve and ascending aorta varied between 5 and 24%, in the majority about 8–10%, but reached 24% after replacement of infected prosthesis [10, 68, 69, 70, 72, 75, 83, 94, 98, 99, 100, 101]. Mortality after elective AVA or xenograft implantation was reported as similar: 5.0% and 4.9% , but varied between 8 and 29% after xenograft and 3–23 after mechanical prosthesis implantation for treatment of endocarditis . After TAVR repair of AVA, was 9% . AVA application is reckoned as connected with greater mortality than the use of other prostheses . The main predictors of early mortality are: emergency, older age (general risk factor), prolonged extracorporeal circulation, low left ventricular function, infection, cerebrovascular diseases, hypertension, pre-operative pacing, terminal renal insufficiency, valve size [61, 69, 70, 76, 93, 96, 98].
8.2.3 Late mortality
Freedom from late mortality after fresh and cryopreserved AVA implantation was comparable after 1, 5, 10, 15, 20 and 25 years, being 81–94%; 65–93.3%; 63–93%, 61–97.7%; 41–69% and 52%, respectively [7, 9, 10, 41, 44, 59, 62, 65, 70, 71, 81, 83, 94, 99]. It was markedly better after implantation of free-hand AVA than of mounted on a stent, 80% versus 69% after 10 years, . The 3 years survival was referred as better after AVA than prosthetic valve implantation, 94% versus 63–82% , while in other papers, 44% after 10 years, independently to the valve type . The probability of mortality has been estimated at 1,68 after AVA versus 5.7 patient/year after xenograft implantation . In patients operated for endocarditis, the 1-, 5, 10- and 15-year survival was of 67–92%; 48–85%; 44–77%; and 53.8%; and did not depend to the type of valve [69, 70, 72, 75, 76, 100]. Meantime, the 20-year survival after surgery for endocarditis on native valve occurred much better than on prosthesis, 44% versus 16% only . In patients with noncomplicated ascending aorta aneurysm, the 5-, 10-, 15-, and 20-year survival was announced of 82.5%; 78.3-87.3%; 70.8%; and 63.6-68.3%; while in De Bakey type II dissection 90%, 75% and 50%, as well as in type I 75%, 75% and 35%, after 5, 10, and 15 years [91, 92, 94]. The survival dependent on the patients’ age at the operation was estimated at 24, 22, and 14 years for the groups aged 20–39; 40–59; and 60–81 years, respectively . According to the operative technique, the average survival was 21, 18, and 16 years after subcoronary, cylinder, or root AVA implantation . As the predictors for late mortality are listed: age > 65 years, creatine level > 150 mmol/l, NYHA class III/IV, left ventricular ejection fraction <40%, coronary disease, severe aortic insufficiency DeBakey type I aorta dissection, and endocarditis [61, 76, 81, 91, 95].
Similarly, to the other biologic valves, 10–15 years after AVA implantation may occur important morphologic changes, worsening the clinical and echocardiographic parameters [10, 61]. The predominant causes of AVA failure are structural valve degeneration in about 80%, and endocarditis in 15% [10, 61, 62, 90]. The AVA incompetency occurs most frequently, in over 60%, but calcified stenosis in about 17% [25, 89]. Freedom from redo surgery at 1, 5, 10, 15, 20 and 25 years has been estimated at 100%; 81–100%; 72–97%; 47–89.4; 15.5–77%; and 35–49.5%, respectively [1, 7, 9, 10, 39, 44, 60, 62, 89, 92, 99]. If compare cryopreserved AVA with fresh AVA and xenografts, the 10 years results were estimated as similar or better (80–92% versus 80–83%) [39, 44, 91]. Late reendocarditis is relatively rare: 0–7% after 5 years. Freedom from it, after 10, 15, 20 and 25 years was 82–97%; 91.9; 77–91.5%; and 70–94%, respectively [5, 7, 11, 44, 60, 61, 62, 69, 71, 72, 76, 99, 100]. Estimated risk of this pathology was 0.15%/patient/year . The durability of AVA depends also to the patients’ age at the operation; it was two times shorter in the aged 25, as compared with 65 years old: 12 versus 23 years. [39, 43]. Freedom from AVA failure after 10 and 20 years in age groups of: <2o; 20–40; 40–60; and 60–80 years, was of 47 and 20; 85 and 69%; 94 and 82%, respectively. These data confirm the general observation that young patients are not good recipients of AVA [61, 64, 99]. Durability according to Ross, cylinder and full root techniques after 10, 20 and 25 years did not differ markedly and amounted: 85, 85 and 80%, versus 60, 55 and 55%, and 55, 45 and 55% . There have been reported patients with AVA functioning 30 years [44, 99], while in our Institution achieved 34 years.
8.2.5 Own selected cohort
A group of 70 patients, in whom in the years 2007–2012 I implanted cryopreserved AVA after modified indications and technique, was analyzed after 1–14, in average 11 years. Extraordinary was 57% participation of women, and more advanced age, in average 73 years (35–89), while 7 patients were > 80 years. Aggressive endocarditis developed in 7 patients, with 3 aorto-right ventricular fistulas.
In NYHA class III were 49, and in IV 21 patients; 7 underwent surgery in accelerated mode. Bicuspid native aortic valve presented 19 patients (27%), but also 37 needed additional procedures: mitral valve decalcification (18), mitral plasty (2), CABG (7), occlusion of intracardiac fistula (3), pacemaker implantation (3), plasty of aortic annulus (2), exstirpation of left atrial myxoma (1), and carotic endarterectomy (1). All patients had advanced left ventricular hypertrophy. They were affected with additional diseases, as arterial hypertension in 70%, coronary disease, diabetes, arrhythmias, asthma, etc. In 69 patients I implanted AVA subcoronary, after own modification of the Ross method. I incised the aorta near to the annulus to facilitating implantation; instead of multiple stitches I used one continuous Prolene 4/0 suture on annular level, thus only 3 running sutures, knoted outside of the aorta, were enough for completion of surgery. The diameter of AVA varied between 19 and 27, in average 22.5 mm. In a patient with Marfan’s syndrome, I replaced AVA full root after 27 years, using frozen graft, with very good result after 14 years. Early mortality of 12.8%, affected patients aged 48–81, on average 73 years, and was caused by sepsis (1), circulatory insufficiency (4), non-aortic bleeding (3), multiorgan failure (1).
In all patients AVA function, estimated echocardiographically was normal, and none death was valve related. All survivors presented permanent or temporary clinical improvement and quality of life. Echo controls showed the good function of grafts: none or trivial AVA incompetency, but II/III° in several cases. Evident graft calcification was unique, massive occurred in 2 of 4 patients who were reoperated after in average 8 years, with on death. One patient aged 37, passed redo surgery for subcoronary AVA after 7, and re redo after 8 years (xenograft); both AVA showed massive calcification, rapidly accelerated during the final year. Late mortality, concerned 22 patients, aged 48–94, in average 77.5 years, after 1–13, in average 6,5 years, was caused with circulatory insufficiency (5), coronary disease (4), neoplasia (4), age and related troubles (9). Summarizing, frozen AVA presented satisfactory results even in older patients with concommittant morbidity, and in extreme tissue damage due to endocarditis; as well as the low rate of redo surgery. The modification of implantation technique allowed for the reduction of mineralization, therefore markedly improved AVA durability, as compared with other patients’ series.
9. Closing remarks
The actual state of research for ideal valve substitutes shows, that there do not exist such valves. The contemporary mechanical prostheses present excellent durability, but still need life-long anticoagulation, while the xenografts offer wide possibilities of use, but limited durability. Both are widely available, universally applied and easy for surgical implantation. Therefore, AVA occurred as grafts being more approximate to the ideal. They are natural, viable, unstented human valves, prepared without the use of strong chemicals. Deep freezing is the optimal technology for preservation. The hemodynamic functions are like native valve. AVA produce no hemolysis nor thromboembolism, and anticoagulation is not necessary; therefore, may be used in patients with contraindications for such therapy. Thanks to marked resistance for infection, are recommended as the best substitutes for endocarditis with severe tissue damage. The clinical results are satisfactory; quality of life is declared as firmly improved, parallelly to high graft acceptance. Indeed, there exist important disadvantages and limits, and AVA are rarely implanted. The availability is markedly limited, both from forensic autopsies and transplant procedures. The durability of AVA is comparable with xenografts, and may be fully accepted, especially for older persons. On contrary, the results in young patients or chronically hemodialyzed, suggest poor indications in these groups. For the application of AVA is necessary to full access to well-equipped laboratory and tissue bank. The initial expenses for their organization are subsequently followed with these of staff and utilization, therefore the costs of AVA preparation may be even two times greater than the price of xenograft or mechanical valve. AVA being not recommended for routine use, should be reserved for experienced centers and surgeons. Implantation and replacement of AVA may occur as a challenge. For AVA application is therefore necessary to meet following requirements: will, may and can. They are connected also with the surgeon’s abilities, including patience, precision, as well as geometric imagination. The mechanical valves and xenografts are still developed and improved. On the contrary, the technologies for AVA preparation appear to attain the limits of their development. Thus, in correlation to the above, the future of AVA employment may be called in question, inspite of their excellence.
Svensson LG et al. Aortic valve and ascending aorta guidelines for management and quality measurement. The Annals of Thoracic Surgery. 2013; 95:S1-S66. DOI: 10.1016/j.athoracsur.2013.01.053
Bidar E, Folliguet T, Kluin J, Muneretto C, Paroleri A, Basili F, et al. Postimplant biological aortic prosthesis degeneration: Challenges in transcatheter valve implants. European Journal of Cardio-Thoracic Surgery. 2019; 55:191-200. DOI: 10.1093/ejcts/ezy391
Kostyunin AE, Yuzhalin AE, Rezvova MA, Ovcharenko EA, Glushkova TV, Kutikhin AG. Degeneration of bioprosthetic heart valves: Update 2020. Contemporary review. Journal of the American Heart Association. 2020; 9:e018506. DOI: 10.1161/JAHA.120.012506
Gibbon JH Jr. Application a mechanical heart and lung apparatus to cardiac surgery. In: Recent Advances in Cardiovasc Physiology and Surgery Minneapolis. University of Minnesota; 1953. pp. 107-113
Walter D, de Buy TMMH, Meyer R, Hetzer R. The future of heart valve banking and of homografts perspective from Deutsches Herzzentrum Berlin. HSR Proceedings in Intensive Care & Cardiovascular Anesthesia. 2012; 4:97-108
Hopkins RA. Historical development of the use of homograft valves in cardiac reconstructions with allograft valves. In: Hopkins RA, editor. Cardiac Reconstructions with Allograft Valve. Springer Verlag New York Inc; 1989. pp. 3-13. DOI: 10.1007/978-1-4612-3568-21
Doty JR, Salazar JD, Liddicoat JR, Flores JH, Doty DB. Aortic valve replacement with cryopreserved aortic allograft: Ten year experience. The Journal of Thoracic and Cardiovascular Surger. 1998; 115:371-380
Kadner A, Chen RH, Mitchell RN, Adams DH. Homograft crossmatching. Is unnecessary due to the absence of blood group antigens. The Annals of Thoracic Surgery. 2001; 71:S349-S352
Yacoub M, Knight E, Towers M. Aortic valve replacement using fresh unstented homografts. Thoraxchirurgie. 1973; 21:451-457
Stoliński J, Marek G, Marcinkowska Z, Jaskier M, Barecka D, Bartuś K, et al. Allogenic heart valve bank in the Department of Cardiovascular Surgery and Transplantology of Jagiellonian University in Cracow −23 years experience in the treating of aortic valves or aortic root diseases. Cell and Tissue Banking. 2006; 7:175-182. DOI: 10.1007/s10561-004-7989-x
Jashari R, Van Hoeck B, Nykam R, Giffin Y, Fan Y. Banking of cryopreserved arterial allograft in Europe: 20 years of operation in the European homograft Bank (EHB) in Brussels. Cell and Tissue Banking. 2013; 14:589-599
Vahanian A, et al. 2021 ESC/EACTS guidelines for the management of valvular heart diseases: developed by the Task Force for the management of valvular hert disease of the European Society of Cardiology (ESC) and European Association for Cardio Thoracic Surgery (EACTS). 2022; 43:561-632. DOI: 10.1093/eutheartj/ehab395
Lam CR, Aram HH, Munnell ER. An experimental study of aortic valve homograft. Surgery, Gynecology & Obstetrics. 1952; 94:129-138
Murray G. Homologous aortic-valve-segment transplants as surgical treatment for aortic and mitral insufficiency. Angiology. 1956; 7:466-471. DOI: 10.1177/000 3319 75600 700.509
Murtra M. The adventure of cardiac surgery. European Journal of Cardio-Thoracic Surgery. 2002; 21:167-180
Duran CG, Gunning AJ. Method of placing a total homologous aortic valve in the subcoronary position. Lancet. 1962; 2:488. DOI: 10.1016/Soi40-6776(62)90346-x
Ross DN. Homograft replacement of the aortic valve. Lancet. 1962; 2:487. DOI: 10.1016/S0140-6736(62)90345-8
Barratt-Boyes BG. Homograft aortic replacement in aortic incompetence and stenosis. Thorax. 1964; 19:131-150. DOI: 10.1136/thx.19.2.131
Dziatkowiak AJ, Pfitzner R, Andres J, Podolec P, Marek Z, Żarska M. Modified techniques for subcoronary insertion of allografts. In: Yankah et al, editors. Cardiac Valve Allografts 1962-1987. Steinkopff Verlag Darmstadt; 1988:141-147
Ross DN. Replacement of aortic and mitral valves with pulmonary autograft. Lancet. 1967; 2:956-958
O’Brien MF, McGiffin DC. Aortic and pulmonary allografts in contemporary cardiac surgery. Advances in Cardiac Surgery. 1990; 1:1-24
McClure GR, Belley-Cote EP, Um K, Gupta S, Bouhout I, Lortie H, et al. The Ross procedure versus prosthetic and homograft aortic valve replacement: A systematic review and meta-analysis. European Journal of Cardio-Thoracic Surgery. 2019; 55:247-255. DOI: 10.1093/ejcts/ezy247
Gerosa G, Ross DN, Brucke PE, Dziatkowak A, Mohammad S, Norman D, et al. Aortic valve replacements with pulmonary homografts. Early experience. The Journal of Thoracic and Cardiovascular Surgery. 1994; 107:424-437
Binet JP, Duran CG, Carpentier A, Langlois J. Heterogenous aortic valve transplantation. Lancet. 1965; 2:1279
Westaby S, Huysmans HA, David TB. Stentless aortic bioprostheses: Compelling data from the second international symposium study. The Annals of Thoracic Surgery. 1998; 65:235-240
Carpentier A, Lemaigre G, Robert L, Carpentier S, Dubost C. Biological factors affecting long-term results of valvular heterografts. The Journal of Thoracic and Cardiovascular Surger. 1969; 58:467-483
Johnston DR, Soltesz EG, Vakil N, Rajesharn J, Roselli EE, Sabik JFIII, et al. Long-term durability of bioprosthetic aortic valves: Implications from 12569 implants. The Annals of Thoracic Surgery. 2015; 99:1239-1247. DOI: 10.1016/j.athoracsur.2014.10.070
Elkins RC, Dawson PE, Goldstein S, Walsh SP, Black KS. Decellularized human valve allografts. The Annals of Thoracic Surgery. 2001; 71:S428-S423
Sarikouch S, Horke A, Tudorache I, Beerbaum P, Werthoff-Blech M, Boethig D, et al. Decellularized fresh homografts for pulmonary valve replacement: A decade of clinical experience. Journal of Cardio-Thoracic Surgery. 2016; 50:281-290. DOI: 10.1093/ejcts/ezw/050
Meyer SR, Nagendran J, Desai LS, Rayat GR, Churchill TA, Anderson CR, et al. Decellularization reduces immune response to aortic valve allograft in rat. The Journal of Thoracic and Cardiovascular Surger. 2005; 130:469-476
Sadowski J, Kapelak B, Pfitzner R, Bartuś K. Sutureless aortic valve bioprothesis 3F/ATS enable −4,5 years of a single Centre experience. Kardiologia Polska. 2009; 67:956-963
Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: First human case description. Circulation. 2002; 106:3006-3008
Lichtenstein SV, Cheung A, Ye J, et al. Transapical transcatheter aortic valve implantation in humans: Initial clinical experience. Circulation. 2006; 114:591-596
Hufnagel CA, Harvey WP. The surgical correction of aortic regurgitation. Bull Georgetown University Medical Center. 1953; 6:60
Harken DE, Soroff HS, Taylor WJ, Lefemine AA, Gupta SK, Lunzer S. Partial and complete prostheses in aortic insufficiency. The Journal of Thoracic and Cardiovascular Surgery. 1960; 40:744-762
Starr A, Edwards ML. Mitral replacement: A critical experience with a ball valve prosthesis. The Annals of Thoracic Surgery. 1061; 154:726-740
Björk VO. Fifty years of cardiac and pulmonary surgery 1942-1993. Scandinavian Journal of Thoracic and Cardiovascular Surgery. 1994;(suppl. 42):1-96
Germain M, Strong DM, Dowling G, Mohr J, Duong A, Garibaldi A, et al. Disinfection of human cardiac valve allografts in tissue banking. Systematic review. Cell and Tissue Banking. 2016; 17:593-601. DOI: 10.1007/S10561-016-9570-9
Wolfinbarger L Jr, Brockbank KGM, Hopkins RA. Application of cryopreservation to heart valves. In: Hopkins RA, editor. Cardiac Reconstructions with Allograft Valves. Springer; 2005. DOI: 10.1007/0-387-26515-5_16
Lisy M, Kalender G, Schenke-Leyland K, Brockbank KGM, Biermann A, Stock UA. Allograft heart valve: Current aspects and future application. Biopreservation and Biobanking. 2017; 15:148-157. DOI: 10.1089/bio.2016.0072
Angell WW, Angell JD, Oury JH, Lamberti JJ, Grehl TM. Long term follow-up of viable frozen aortic homografts, a viable homograft valve bank. The Journal of Thoracic and Cardiovascular Surger. 1987; 93:815-822
Pfitzner R, Barecka D, Pawlikowski M, Kopytek M, Rudnicka-Sosin L, Majewska E, et al. Influence of cryopreservation on structural, chemical and immunoenzymatic properties of aortic valve allografts. Transplantation Proceedings. 2018; 50:2195-2198. DOI: 10.1016/j.transproceed.2018.04.027
Barratt-Boyes BG, Roche AHG, Whitlock RNL. Six years of the results of freehand aortic valve replavement using an antibiotic sterilised homograft valve. Circulation. 1977; 55:353
O’Brien MF, Stafford G, Gardner M, Pohlner P, McGiffin D, Johnston N, et al. The viable cryopreserved allograft aortic valve. Journal of Cardiac Surgery. 1987; 2(suppl. 1):153-167
Yacoub M, Kittle CE. Sterilization of valve homografts by antibiotic solution. Circulation. 1970; 40:II-29
der Kamp V, Visser WJ, van Dongen JM, Nante J, Galjaard H. Preservation of aortic heart valves with maintenance of cell viability. The Journal of Surgical Research. 1981; 30:47-56
Kitagawa T, Matsuda Y, Tominaga T, Kano M. Cellular biology of cryopreserved allograft valves. Journal of Medical Investigations. 2001; 48:123-132
Novotny R, Slizova B, Hlubocky J, Krs O, Spatenka J, Burkert J, et al. Cryopreserved human aortic root allografts arterial wall: Structural changes occuring during thawing. PLODOne. 2018. DOI: 10.1371/journal.pone.0175007
Yankah AC, Wottge HV, Muller-Hermelink HK, Feller AC, Lange P, Wessel U, et al. Transplantation of aortic and pulmonary allografts. Enhanced viability of endothelial cells by cryopreservation, importance of histocompatibility. Journal of Cardiac Surgery. 1987; 2(suppl):209-220
Okkado A, Hashida M, Furukawa H, Lu H, Hanayama N, Hoshi H, et al. Should be aortic valve homograft be recryopreserved? The Annals of Thoracic Surgery. 1998; 65:1083-1086
Iop L, Paolin A, Aguiari P, Trojan D, Cogliati E, Gerosa N. Decellularized cryopreserved allografts as off-the shelf allogenic alternative for heart valve replacement: In vitro assessment before clinical translation. Journal of Cardiovascular Translational Research. 2017. DOI: 10.1007/S 12265-017-9738-0
Podolec P, Drwiła R, Goncerz G, Rokita E, Sadowski J, Tracz W, et al. Fresh-wet storage accelerates aortic homograft calcification. Cell and Tissue Banking. 2007. DOI: 10.1007/S 10561-007-9017-9
Vasquez-Rivera A, Oldenhof H, Dipresa D, Goecke T, Kouvaka A, Will F, et al. Use of sucrose to diminish pore formation in freeze-dried heart valves. Scientific Reports. 2018. DOI: 10.1038/s41598-018-31388-4
Bodnar E, Matsuki O, Parker R, Ross DN. Viable and nonviable aortic homografts in the subcoronty position: A comparative study. The Annals of Thoracic Surgery. 1989; 47:799-808
Fischlein T, Schulz A, Haushofer M, Free R, Utilize A, Detter C, et al. Immunologic reaction and viability of cryopreserved homografts. The Annals of Thoracic Surgery. 1995; 60:S122-S126
Pompilio G, Polvani GL, Piccolo G, Guarino A, Veglia F, Sala A, et al. Six-year monitoring 0f donor-specific immune response to cryopreserved allograft valves; suplications with valve dysfunction. The Annals of Thoracic Surgery. 2004; 78:557-563
Johnson DL, Rose ML, Yacoub MH. Immunogenicity of human heart valve endothelial cells and fibroblasts. Transplantation Proceedings. 1997; 29:984-985
Clarke D, Campbell D, Hayward A, et al. Degeneration of aortic valve allografts in young recipients. The Journal of Thoracic and Cardiovascular Surgery. 1993; 105:934-942
Yacoub MH. Applications and limitations of histocompatibility in clinical cardiac surggery. In: Yankah AC et al., editors. Cardiac Valve Allografts 1962-1983. New York Springer Verlag; 1985. pp. 89-94
Feingold B, Wearden PD, Morell VO, Galvis D, Galambos O. Expression of a and B blood group antigens on cryopreserved homografts. The Annals of Thoracic Surgery. 2009; 87:211-214
Fukushima S, Tesar PJ, Paerse B, Jalali H, Sparks L, Freser JF, et al. Long-term clinical outcomes after aortic valve replacement using cryopreserved aortic allografts. The Journal of Thoracic and Cardiovascular Surger. 2014; 148:65-72. DOI: 10.1016/jtsvs.2013.07.038
Solari S, Mastrobuoni S, De Kerchove L, Navarra E, Astarci P, Noirhomme P, et al. Over 20 years experience with homograft in aortic valve replacements during acute infective endocarditis. European Journal of Cardio-Thoracic Surgery. 2016; 50:1158-1162. DOI: 10.1093/ejcts/ezw179
Dziatkowiak AJ, Pfitzner R, Sadowski J, Tracz WD, Koziorowska B, Marek Z, et al. Aortic root replacement using antibiotic sterilized “fresh” unstented homografts: Modification of annulus reinforcement. In: Bodnar E et al., editors. Biologic & Bioprosthetic Valves. Vol. 3. New York: Yorke Med. Books; 1986. pp. 14-21
O’Brien MF, Harrocks S, Stafford EG. The homograft aortic valve. The Journal of Heart Valve Disease. 2001; 10:334-345
Takkenberg JJ, Klieverik LM, Bekkers JA, Eikemans MJC, Bogers AJJC, Kappetein AP, et al. Allografts for aortic valve or root replacement: Insights from an 18 year single Centre prospective follow-up study. European Journal of Cardio-Thoracic Surgery. 2007; 31:851-859
Langenay T, Flecher E, Fouquet O, Ruggiers VG, De La Tour B, Felix C, et al. Aortic valve replacement in the elderly. The real life. The Annals of Thoracic Surgery. 2012; 93:70-84
Raggi P, Boulay A, Charan-Taber S, Aurin N, Dillon M, Burke SK, et al. Cardiac calcification in adult hemodialysy patients link between end-stage renal diseases and cardiovascular disease? Journal of the American College of Cardiology. 2002; 39:695-701
Wallace AG, Young WG, Osterhout S. Treatment of acute bacterial endocarditis by valve excision and replacement. Circulation. 1965; 31:450-453
Perotta E, Zubrytska Y. Valve selection in aortic valve endocarditis. Polish Journal of Cardio-Thoracic Surgery. 2016; 13:203-209
Sabik JF, Lytle BW, Blackstone EM, Marullo AGM, Petterson GB, Cosgrove DM. Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis. The Annals of Thoracic Surgery. 2002; 74:650-659
Lopes S, Calvinho P, de Oliveira F, Antunes M. Allograft aortic root replacement in complex prosthetic endocarditis. European Journal of Cardio-thoracic Surgery. 2007; 32:126-132. DOI: 10.1016/j.ejcts.2007.01.076
Moon MR, Miller DC, Moore KA, Oyer PE, Mitchell RS, Robbins RC, et al. Treatment of endocarditis with valve replacement: The question of tissue versus mechanical prosthesis. The Annals of Thoracic Surgery. 2001; 76:1164-1171
Avierinos JF, Thuny F, Chalvignac V, Giorgi R, Tafanelli L, Casalta JP, et al. Surgical treatment of active aortic endocarditis: Homografts are not cornerstone of outcome. The Annals of Thoracic Surgery. 2007; 84:1935-1942. DOI: 10.106/j.athoracsur.2007.06.050
Musci M, Weng Y, Hubler M, Amiri A, Pasic M, Kosky S, et al. Homograft root replacement in native or prosthetic active infective endocarditis: Twenty-year-single-center experience. The Journal of Thoracic and Cardiovascular Surger. 2010; 139:665-673. DOI: 10.1016/j.jtcvs.2009.07.026
Flameng W, Daenen W, Jashari R, Herijgers P, Meuris B. Durability od homografts used to treat complex aortic valve endocarditis. The Annals of Thoracic Surgery. 2015; 99:1234-1238. DOI: 10.1016/jathoracsur.2014.11.012
Grinda J-M, Meinardi J-L, D’Attelis N, Bricourt M-O, Barrebi A, Fabiani J-N, et al. Cryopreserved aortic viable homograft for active aortic endocarditis. The Annals of Thoracic Surgery. 2005; 79:767-771. DOI: 10.1016/j.athoracsur.2004.08.013
Dearani JA, Orszulak TA, Daly RC, Philips MR, Miller FA, Danielson GK, et al. Comparison of techniques for implantation of aortic valve allografts. The Annals of Thoracic Surgery. 1996; 62:1067-1075
McGiffin DC, Kirklin JK. Homograft aortic valve replacement: The subcoronary and cylindrical techniques. Operative Techniques in Cardiac and Thoracic Surgery. 1997; 42:255-265
Northrup WFIII, Koshettry VR. Implantation techniques of aortic homograft root: Emphasis on matching the host root. The Annals of Thoracic Surgery. 1998; 66:280-284
Khalpey Z, Borstlap W, Myers PO, Schmitto JD, Mc Gurk S, Maloney A, et al. The valve-in-valve operation for aortic homograft dysfunction: A better option. The Annals of Thoracic Surgery. 2012; 94:731-736. DOI: 10.1016/j.athoracsur.2012.04.019
Somerville J, Ross DD. Homograft replacement of aortic toot with reimplantation of coronary arteries. Results after one to five years. British Heart Journal. 1982; 47:473-482
Kowert A, Vogt F, Berias-Fernandez A, Reichart B, Kilian E. Outcome after homograft redo operation in aortic position. European Journal of Cardio-thoracic Surgery. 2012; 41:404-408. DOI: 10.1016/j.ejcts.2019.04.043
Sedeek AF, Greason KL, Nkomo VT, Eleid MF, Maltais S, Williamson EE, et al. Repeat valve replacements for failing aortic root homografts. The Journal of Thoracic and Cardiovascular Surger. 2019; 158:378-385. DOI: 10.1016/j.jtcvs.2018.11.102
Liao KK, Li X, John R, Amatya DM, Jouce LD, Park SJ, et al. Mechanical stress: An independent determinant of early bioprosthetic calcification in humans. The Annals of Thoracic Surgery. 2008; 86:491-495. DOI: 10.1016/j.athoracsur.2008.03.061
Natorska J. Diabetes mellitus as a risk factor for aortic stenosis: From new mechanisms to clinical applications. Kardiologia Polska. 2021; 79:1080-1067
Pawlikowski M. Biomineralization of heart valves. Journal of Clinical Review and Case Reports. 2019; 4:1-6
Lis GJ, Rokita E, Podolec P, Pfitzner R, Dziatkowiak A, Cichocki T. Mineralization and organic phase modifications as contributory factors od accelerated degeneration in homograft aortic valves. The Journal of Heart Valve Disease. 2003; 1:741-751
Huitema LFA, Vaandrager AB. What triggers cell-mediated mineralization. Frontiers in Bioscience. 2007; 12:2631-2645
Arabkhani B, Bekkers JA, Andrianopoulou E-R, Roas-Hesselink JW, Takkenberg JJM, Bogers AJJC. Allografts in aortic position: Highlights from a 27 year single-center prospective study. The Journal of Thoracic and Cardiovascular Surger. 2016; 152:1572-1579. DOI: 10.1016/j.jtcvs.2016.08.053
Sadowski J, Kapelak B, Bartuś K, Podolec P, Rudziński P, Myrdko T, et al. Reoperation after fresh homograft replacement: 23 years experience with 655 patients. European Journal of Cardio-thoracic Surgery. 2003; 23:996-1001. DOI: 10.1016/S 1010-7940(83)00109-x
Podolec P, Tracz W, Kostkiewicz M, Sadowski J, Hlawaty M, Olszowska M, et al. Clinical and echocardiographocal study on the aortic homografts implantations in patients with Marfan syndrome. International Journal of Cardiology. 1997; 60:41-47
Kirklin JK, Smith D, Novick W, Naftel DC, Helmcke FR, Bourga R. Long-term function of cryopreserved aortic homografts. A ten-year study. The Journal of Thoracic and Cardiovascular Surger. 1993; 105:154-166
Podolec P, Pfitzner R, Sadowski J, Kostkiewicz M, Tracz W, Dziatkowiak A. Long-term results of aortic root replacement with aortic allograft in patients with dissection of the ascending aortic wall. Bologna: International Proceedings of XIII World Congress Cardiol. Rio de Janeiro 1998. Monduzzi Ed; Bologna: Free papers; 1998:1119-1125
Maselli D, Pizio R, Bruno LP, Di Bella I, De Gaspari C. Left ventricular mass reduction after aortic valve replacement: Homografts, stentless and stented valves. The Annals of Thoracic Surgery. 1999; 67:966-971
Podolec P, Pfitzner R, Wierzbicki K, Kostkiewicz M, Tracz W, Dziatkowiak A. The quality of life after aortic valve replacement with homografta or prosthetic valve. The Journal of Heart Valve Disease. 1998; 7:270-276
Dossche KM, Brutel de la Riviere A, Morshuis WJ, Schepens M, Defauw JJAM, Ernst SM. Cryopreserved aortic allografts for aortic root reconstruction: A single Institution’s experience. The Annals of Thoracic Surgery. 1999; 67:1617-1622
Nappi F, Nenna A, Petitti T, Spadaccio C, Gambardella I, Chello LM, et al. Long-term outcome of cryopreserved allograft for aortic valve replacement. The Journal of Thoracic and Cardiovascular Surger. 2018; 156:1357-1363. DOI: 10.1016/jtcvs.2018.04.040
Huygens SA, Mokhles MM, Hanif M, Bekkers JA, Bogers AJJC, Rutter-van Molken MPMH, et al. Contemporary outcomes afret surgical aortic valve replacements with bioprostheses and allografts: A systematic review and metaanalysis. European Journal of Cardio-Thoracic Surgery. 2016; 50:605-616. DOI: 10.10193/ejcts/ezw101
Hickey E, Langley SM, Allemby-Smith O, Livesay SA, Monro JL. Subcoronary allograft aortic valve replacement: Parametric risk-hazard outcome analysis to a minimum 20 year. The Annals of Thoracic Surgery. 2007; 84:1567-1570. DOI: 10.1016/j.athoracsur.2007.02.100
Yankah AC, Pasic M, Klose H, Siniawski H, Weng Y, Hetzer R. Homograft reconstruction of the aortic root for endocarditis with periannular abscess: A 17 year study. European Journal of Cardio-Thoracic Surgery. 2005; 28:68-74
Khaladj N, Pichlmaier U, Stachmann A, Peterss S, Reichelt A, Hagl C, et al. Cryopreserved human allografts (homografts) for the management of graft infections in the ascending aortic position extending to the aortic arch. European Journal of Cardio-Thoracic Surgery. 2013; 43:1170-1175. DOI: 10.1093/ejcts/ezs 572