Aortic Valve Homograft Research Articles

Construction of Tissue-Engineered Homograft Bioprosthetic Heart Valves In Vitro

Human mesenchymal stem cells (MSCs) differentiate into multiple cell-lineages and may serve as an alternative source of seed cells for tissue engineering. We investigated whether MSCs could be induced to differentiate into endothelial cells (ECs) and function as seed cells for the in vitro construction of tissue-engineered heart valves (TEHVs). Aortic or pulmonary valve homografts were decellularized with 0.1% sodium dodecylsulphate and used as scaffolds for TEHVs. The MSCs were isolated from human bone marrow by Percoll gradient centrifugation (1.073 g/ml), differentiated into ECs with vascular endothelial growth factor (10 ng/ml), and seeded onto a decellularized scaffold (high-density seeding, >10(5) cells/cm2) and grown in static culture for 14 days. Over 90% of the differentiated cells from MSCs stained positively for von Willebrand factor and Tie-2-related antigen. Additionally, Weibel-Palade corpuscle was observed in the cytoplasm of these cells. Levels of reendothelialization in static culture on days 7, 14, and 20, were 73%, 85%, and 95%, respectively. These results show that MSCs from human bone marrow can differentiate, in vitro, into ECs that can then be used to construct TEHVs. Reendothelialization in static culture can be used to provide the basic material for pulsatile-flow cultivation.

Norman E. Shumway, M.D., Ph.D. (1923 – 2006) Surgical Innovator

Norman E. Shumway, M.D., Ph.D. (1923 – 2006) Surgical Innovator

Invited commentary

In this article [1] the authors compared the outcomes of two techniques of implantation of aortic valve homograft for aortic valve replacement (AVR) (ie, aortic root replacement [RR] with aortic root preservation [RP]. They included the techniques of subcoronary implantation (with or without preservation of the noncoronary aortic sinus of the homograft) and aortic root inclusion under the same group. I do not know enough biostatistics to judge Grunkemeier’s methodology for a meta-analysis on 11 nonrandomized clinical reports of such complex, varied, and heterogeneous patient population as AVR with aortic valve homograft.

Heart valve donation in two small infants

The shortage of small donor heart valves forces surgeons to use mechanical heart valves as the second-best option for valve replacement in infants. This shortage of small donor heart valves originates primarily in the unawareness of physicians of the possibility of heart valve donation in infants [2]. In view of the current shortage of small donor heart valves we report here on two cases of heart valve donation in small infants in an attempt to increase physicians’ awareness of the problem. Case 1 was a 6-month-old male infant who developed a septic shock during screening for orthotopic liver transplantation for end-stage liver failure due to biliary atresia. He was admitted to the pediatric intensive care unit, where he eventually died of ongoing sepsis. In light of their son’s possible liver transplantation the parents had studied the matter of donation extensively and requested that his heart valves be harvested for donation. They were aware that bacterial cultures would have to be performed and that the valves would have to be discarded if a micro-organism was cultured. Cultures remained negative, and 8-weeks later the pulmonary valve was successfully implanted in a 5-weekold male infant. Case 2 was a 5-week-old male infant with a history of severe neonatal epilepsy who was admitted to the pediatric intensive care unit because of respiratory failure. Severe brain damage without the possibility of meaningful recovery was diagnosed on the basis of the clinical picture and electroencephalograms (EEG’s). Intensive care was withdrawn, and the infant died. Having become aware of the possibility of tissue donation in infants by the parents of the infant described in case 1, we asked the parents to consider heart valve donation. They agreed under the condition that the heart would be returned in time for the funeral. After consultation with the Bio Implant ServicesFoundation (BIS-Foundation), which is the intermediary in the donation and allocation of human tissues for The Netherlands, Belgium, Germany, Slovenia and Austria, we were able to provide this guarantee. Ten weeks later the aortic valve was successfully implanted in a 10-day-old female infant. Most people who die are able to donate tissue, and in this respect tissue donation differs substantially from organ donation. Organ donation remains primarily restricted to the Intensive Care Unit (ICU), despite the recent development of non-heart-beating organ donation. For this reason, the pool of potential tissue donors is much larger than the pool of potential organ donors. However, despite this large pool, shortage of donor tissues exists [1, 2]. Tissue donation involves the cornea, skin, bone and heart valves. In children, tissue donation is limited to the cornea (in children over 2 years of age) and heart valves. Because of size and maturation issues, the donation of skin, cartilage and bone is only possible in individuals over 16 years of age. In infants the main indications for valve replacement are critical aortic valve stenosis and right outflow tract abnormalities (i.e. pulmonary atresia, truncus arteriosus and severe tetralogy of Fallot). In critical aortic stenosis, the Ross procedure is the operative technique of choice: the patient’s own pulmonary valve serves as an autograft for the stenotic aortic valve, and an appropriately sized pulmonary or aortic valve allograft is used to replace the pulmonary valve [5]. Autografts are preferred because they J. K. Kieboom (*) Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands e-mail: j.k.w.kieboom@bkk.umcg.nl Tel.: +31-50-3614294 Fax: +31-50-3614235

Percutaneous occlusion of a pseudoaneurysm evolving after homograft aortic valve and root replacement with the Amplatzer muscular ventricular septal defect occluder

of an early aggressive treatment was life saving. Compared with the scheduled device implantation in patients deteriorating on the waiting list, management of emergencies requiring circulatory support is still a challenging situation. We have developed in our unit a mobile kit of emergency circulatory support to deal with this problem. This ECLS has become a useful adjunct to our cardiac assist device program, allowing patient transfer and secondary implantation of a more long-term sophisticated device. As expected in this catecholamine-induced cardiomyopathy, the patient recovered after surgical resection of the tumor, but recovery is not so fast as to allow the use of an ECLS device alone, and implantation of a long-term device was mandatory.

Are allografts the biologic valve of choice for aortic valve replacement in nonelderly patients? Comparison of explantation for structural valve deterioration of allograft and pericardial prostheses

To compare explantation for structural valve deterioration in nonelderly patients after aortic valve replacement with stented bovine pericardial and cryopreserved allograft valves. From 1981 to 1985, 478 patients received pericardial prostheses during premarket approval; from 1987 to 2000, 744 patients received cryopreserved allografts. Mean age of patients receiving allografts was 49 +/- 12 years, and that of those receiving pericardial prostheses was 65 +/- 11 years; pericardial valves were used in 138 patients younger than age 60. Mean follow-up was 15 +/- 5.1 years for pericardial valves (4674 patient-years of follow-up) and 5.6 +/- 3.1 years for allografts (3892 patient years of follow-up). Multivariable hazard function methodology, age-group stratification, and propensity matching were used to compare age-specific explantation for structural valve deterioration. Ninety-five pericardial valves and 46 allografts were explanted, and structural valve deterioration was the mechanism of failure in 74% and 59%, respectively. The risk of structural valve deterioration increased with younger age at implantation for both allografts (P = .07) and pericardial valves (P < .0001), with a similar magnitude of effect in patients age 50 years or younger (P = .5), 50 to 60 years (P = .7), and greater than 60 years (P = .9) and in propensity-matched pairs (P = .2). Thus, pericardial valves were as durable as allografts at all adult ages. Structural valve deterioration is the most frequent cause of valve-related reoperation after both pericardial and allograft aortic valve replacement and is similarly age dependent, suggesting that pericardial valves may be appropriate for nonelderly as well as older persons.

The decrease of degeneration rate by means of a permanent antithrombotic theraphy 16 and more years after the biological aortic valve replacement

Aims: In view of the main deficiency of biological valve prostheses – their frequent degeneration, we analysed the impact of a permanent post-operative antithrombotic therapy (PPATT) after the aortic valve replacement with biological prostheses (BAVP) on their degeneration rate among 142 patients who had been operated on with aortic valve replacement with biological prostheses (141 Carpentier-Edwards porcine prostheses and 1 allograft aortic valve) between July 1976 and December 1980 in our clinic.

The Ross Operation — An Evolutionary Tale

The Ross operation has many unique and intricate features, which need to be defi ned and understood if the operation is to achieve its potential. Although the operation was described nearly 35 years ago, it has continued to evolve through gradual understanding of the complex but elegant anatomic and physiological processes involved in execution of the operation as well as adaptation of the pulmonary valve to its new environment, coupled with the application of sophisticated methods of analysing the results of the operation. All of this has resulted in the accumulation of a large amount of knowledge, which strongly suggests that this operation could have an important, unique and wider role to play in the fi eld of valve surgery provided that certain details are adhered to. Some of this knowledge is reviewed in this editorial. Detailed studies of the form and function of the normal aortic valve have shown that this valve performs extremely sophisticated functions which depend largely on the biological properties of the valve at cellular and molecular level 1-4 and are critically dependent on continued viability of the valve. The Ross operation is the only form of valve replacement which guarantees viability of the valve substitute both in the short and long term. We theorise that this should translate into clinical benefi t both in terms of survival and quality of life. Recent studies using microsimulation to compare the pattern of survival of the Ross operation to the general population, have shown similar pattern of survival in the two groups which is signifi cantly better than that observed after aortic valve replacement using other types of substitutes. 5 Excellent postoperative survival after the Ross operation have been described by several authors 6,7 including the article published in the “journal”. 8 Although it could be argued that these fi ndings are due to patient selection, many of the reported series have included a signifi cant number of high-risk patients such as those with active infective endocarditis or redo operations. Furthermore a prospective randomised trial to compare the Ross operation to homograft has shown enhanced survival after the Ross operation 9 confi rming the notion that continued viability of the valve can translate into major clinical benefi t. Further larger prospective randomised trials, possibly multi centre are needed to confi rm or refute these potentially important preliminary observations. Other aspects of the Ross operation which has evolved concern major technical modifi cations and refi nements of the technique of explantation and insertion of the pulmonary autograft to minimise coronary and myocardial injury during explantation and attempt to eliminate the incidence of late dilatation of the autograft while avoiding the use of any foreign prosthetic material such as Tefl on or Dacron strips which could defeat the purpose of the operation. The original Ross operation involved insertion of the autologous pulmonary valve in the subcoronary position using two suture lines. This technique has the theoretical advantage of retaining normal aortic wall around the autograft which is thought to prevent progressive dilatation of the autograft root. This technique however has the potential of distorting the autograft. Although valves inserted by this technique can last for periods of up to 35 years, 10 we have observed calcifi cation in one of the cusps of the autograft which had to be due to abnormal movements of the cusps secondary to distortion. The technique of full aortic (or pulmonary) root replacement was originally introduced to maintain the exact relationship of the semilunar valve mechanism 11 and have been shown to be an independent predictor of better survival and less degeneration following aortic homograft valve replacement. 12 If that technique is used however, we believe that it is essential to use multiple interrupted sutures for the lower suture line with scalloping of the autograft to allow the hinge mechanism to be supported by the native aortic annulus. Another evolutionary point in the Ross operation is the inherent capacity to adapt to the new environment by altering its structure and physical properties. 13 This however, does not occur immediately after the operation and therefore the newly implanted autograft root should not be subjected to pressure higher than 110/80 which could predispose to progressive root dilatation and/or chronic dissection of the arterial wall of the pulmonary autograft root.

The fate of aortic valve homografts. An experimental study.

Abstract Segments of homograft aortic valve cusp and aortic sinus wall have been inserted as patches in the abdominal aortic wall of sheep. The donor valves were prepared in one of three ways: (1) fresh valves, (2) freeze-dried valves sterilized with antibiotics and ethylene oxide, and (3) valves which had been cooled at a controlled rate to – 70°C. in a medium containing the cryoprotective agent, dimethyl sulphoxide. Histological examination of the implanted tissue obtained at intervals up to 2 years failed to show survival of any donor cells, whichever method of preparation had been used. The elastic tissue in the freeze-dried series had become calcified by 2 years, and although valves prepared in this way appeared to elicit no immunological response, both the fresh and frozen tissue were infiltrated by lymphocytes and plasma cells by 2 weeks. This round-cell infiltration reached a peak at 4 weeks and then subsided again. The response to fresh valves was more marked and more prolonged than that to frozen valves.

Long-term preservation of fresh viable aortic valve homografts by freezing.

Abstract A method of long-term storage of fresh homograft heart valves in liquid nitrogen (−195 °C) is described. The object is to preserve them in a viable state with unchanged structure. Five groups of valves were studied. Viability before and after freezing was assessed quantitatively by the use of autoradiography. Mitotic activity of the fibroblasts declined at a very slow rate in groups 1, 2, 3 and 4, in which the valves were stored at +4 °C in a nutrient/antibiotic solution for periods between 24 hours and up to 6 weeks before freezing. The percentage of metabolically active fibroblasts declined more rapidly in valves from group 5, in which the valves had been stored for 8 weeks at +4 °C before freezing.

Associated Coronary Anomalies in 135 Iranian Patients with Tetralogy of Fallot

Coronary artery anomalies are common among patients with tetralogy of Fallot. One hundred and thirty-five patients (80 males and 55 females) with tetralogy of Fallot who underwent repair between 1995 and 2002 were studied to determine the incidence of coronary anomalies in Iranian patients. Eight (5.9%) patients (4 males and 4 females) had a surgically relevant coronary artery anomaly: single coronary ostium in 5, origin of the left anterior descending artery from the right coronary artery in 2, and origin of the right coronary artery from the left coronary artery in 1. The surgical technique in 3 of these patients was repair of the ventricular septal defect with a transverse incision on the right ventricle, without damage to the coronary arteries. In another patient, an allograft aortic valve cylinder was inserted. In the other 4 patients with a single coronary ostium, placement of a limited transannular patch was adequate. Consideration of these anomalies during primary repair could decrease the risk of operation in such patients. However, it seems that the presence of anomalous coronary arteries does not affect incremental risk after surgical repair.

Long-Term Results of Apical Aortic Conduits in Children With Complex Left Ventricular Outflow Tract Obstruction

Apical aortic conduits were used in children with complex left ventricular outflow tract obstruction at our institution before we adopted the Ross and Ross-Konno procedures. The early results with apical aortic conduits were quite good when we used a porcine xenograft conduit and were less satisfactory when we converted to an aortic homograft valve as the conduit valve. This report summarizes our clinical experience with apical aortic conduits in children with an emphasis on hemodynamic results, reoperation, and long-term follow-up. Records of 28 patients (age range, 2 weeks to 19 years) who underwent insertion of apical aortic conduit between September 1979 and June 1993 were reviewed. All patients had complex multilevel left ventricular outflow tract obstruction. All were symptomatic, and 22 (79%) had had one or two previous aortic valvotomies or left ventricular outflow tract operations, or both. Hospital mortality was 11% (3 of 28). Twenty-five children survived the perioperative period and improved, and 21 have had one or more cardiac catheterization from 6 to 18 months (mean, 1.2 years) after the initial operation. Reduction or resolution of resting mean left ventricular-to-aortic peak gradient in the early postoperative period from 81.8 +/- 24.0 to 15.4 +/- 8.9 mm Hg was demonstrated (p < 0.001). Overall 25-year survival was 57%. Fourteen surviving patients (56%) have undergone subsequent procedures (n = 18) from 5 months to 16 years postoperatively (mean, 6.9 years) because they developed a recurrent left ventricular-to-aortic gradient of 58 +/- 28 mm Hg (p < 0.002). One patient underwent heart transplantation. All other late survivors have normal left ventricular function as determined by serial echocardiography. Apical aortic conduit is effective in relieving complex left ventricular outflow tract obstruction and improving left ventricular performance with acceptable short-term and midterm results, but late complications caused primarily by conduit tissue valve dysfunction are frequent in children. Since the early 1990s, the apical aortic conduit procedure has been largely replaced with the Ross or Ross-Konno procedure in our pediatric practice.

Aortic root replacement with a novel decellularized cryopreserved aortic homograft: Postoperative immunoreactivity and early results

Novel antigen-reduction SynerGraft technology (CryoLife Inc, Kennesaw, Ga) reduces the cellular components of a cadaver homograft with an enzymatic and washing process, leaving the extracellular matrix intact. We report the immunoreactivity (positive panel reactive antibody assay) and early operative results of the CryoLife SynerGraft aortic valve conduit homograft. Twenty-two patients (age 53 +/- 14 years, range 31-80 years) from April 2002 to July 2003 underwent aortic root replacement with a CryoLife SynerGraft aortic valve conduit homograft (CryoLife Inc, Kennesaw, Ga) for congenital or acquired aortic valve disease, aortic aneurysm with aortic valve disease, or native or prosthetic aortic valve endocarditis. Baseline percentage positive panel reactive antibody results were negative (<10%) for all and were assessed at 1 month, 3 months, and 1-year. Homograft function was evaluated by echocardiography. Early mortality was 0%. Two late deaths at 1 postoperative year were unrelated to homograft function. At 1 postoperative month, panel reactive antibody results were negative in 20 patients (91%). At 3 months, 19 of 22 patients (86%) had negative results, including 1 with previous positive results. At 1 year, 19 of 20 patients (95%) had negative results, including 2 of the 3 with previous positive results. The mean aortic valve gradients were 12 +/- 8 mm Hg (n = 21) at discharge and 11 +/- 7 mm Hg (n = 18) at 1 year. At a mean follow-up of 30.3 +/- 5.2 months, the mean gradient was 8.8 +/- 6.3 mm Hg. The SynerGraft decellularization technology successfully removed antigens from an aortic valve homograft conduit. Aortic root reconstruction with the CryoLife SynerGraft aortic valve homograft resulted in low transvalvular gradients, similar to those seen with standard cryopreserved homografts. These early results suggest an advancement in homograft technology. The low panel reactive antibody response may enhance durability by eliminating immune complex-mediated reaction against the homograft. The lack of allosensitization in patients who may require organ transplantation in the future is an added benefit.

Decellularization reduces the immune response to aortic valve allografts in the rat

Cryopreserved valve allografts used in congenital cardiac surgery are associated with a significant cellular and humoral immune response. This might be reduced by removal of antigenic cellular elements (decellularization). The aim of this study was to determine the immunologic effect of decellularization in a rat allograft valve model. Brown Norway and Lewis rat aortic valves were decellularized with a series of hypotonic and hypertonic buffers, protease inhibitors, gentle detergents (Triton X-100), and phosphate-buffered saline. Valves were implanted into Lewis rats in syngeneic and allogeneic combinations. Cellular (CD3 and CD8) infiltrates were assessed with morphometric analysis, and the humoral response was assessed with flow cytometry. Morphometric analysis identified a significant reduction in CD3 + cell infiltrates (cells per square millimeter of leaflet tissue) in decellularized allografts compared with that seen in nondecellularized allografts at 1 (79 +/- 29 vs 3310 +/- 223, P < .001), 2 (26 +/- 11 vs 109 +/- 20, P = .004), and 4 weeks (283 +/- 122 vs 984 +/- 145, P < .001). Anti-CD8 staining confirmed the majority of infiltrates were cytotoxic T cells. Flow cytometric mean channel fluorescence intensity identified a negative shift (abrogated antibody formation) for decellularized allografts compared with nondecellularized allografts at 2 (19 +/- 1 vs 27 +/- 3, P = .033), 4 (35 +/- 2 vs 133 +/- 29, P = .001), and 16 weeks (28 +/- 2 vs 166 +/- 54, P = .017). Decellularization significantly reduces the cellular and humoral immune response to allograft tissue. This could prolong the durability of valve allografts and might prevent immunologic sensitization of allograft recipients.

Three-dimensional in vivo characterization of calcification in native valves and in Freestyle versus homograft aortic valves

This article describes a novel interactive method for quantitative evaluation of calcium deposits in the aortic valve by means of electron beam tomography data fusion technique. The technique relied on the use of hierarchic 3-dimensional free-form volume registration with fast global optimization between normally acquired and contrast-enhanced electron beam tomographic volume. A total of 66 contrast-enhanced electron beam tomographic scans of the aortic root were performed in 27 patients, 10 with native aortic valve disease (group A) and 17 from a prospective randomized trial of aortic root replacement (group B, 9 Freestyle grafts [Medtronic, Inc, Minneapolis, Minn] and 8 homografts). To validate the in vivo electron beam tomographic measurements, 5 patients from group A underwent electron beam tomographic scans before the operation and then had their own valves, explanted at the time of surgery, analyzed for calcium quantification by ex vivo electron beam tomography. In group A, the mean (+/- SE) calcification score was 6560 +/- 2388, which correlated with peak gradients measured at echocardiography ( r = 0.93, P = .02). In group B, the mean (+/- SE) calcification score was 168 +/- 27, showing a tendency toward a lower calcification for Freestyle valves than for homografts at 2 years after implantation ( P = .052). A mean variability of 6% was found between in vivo electron beam tomographic scores of calcification and those measured on valve specimens after explantation. We describe a novel method to characterize the degree and location of calcification in both native valves and postoperative valve implants. The technique may be useful in the management of patients with aortic valve disease and has potential as a screening tool for high-risk patients to diagnose early valve calcification and possibly institute corrective measures.

Lessons from the first patient to undergo full aortic root replacement using a homograft: A 29-year follow-up

Homograft aortic valve replacement (AVR) has been shown to have many advantages over other forms of AVR. The technique of full aortic root replacement, introduced by us in 1975, has the potential to reproduce, at least in part, the normal native aortic valve behavior. There is, however, a debate about the early and long-term results of this operation, particularly in relation to overall valve performance, aortic root dilatation and calcification, left ventricular function, fate of coronary anastomoses, sensitization against allograft, and any other complications. Although we report about a single patient, this study represents the longest follow-up for this operation, which is of historical value and could provide some valuable insights.

Tissue Engineering of Heart Valves

In 1956, Gordon Murray first reported the human clinical surgical use of fresh aortic valve homografts (cadaveric) transplanted into the descending thoracic aorta for clinical amelioration of the consequences of native aortic valve insufficiency.1 His initial operation preceded by 5 years the availability of mechanical aortic valve prostheses. Although the operation was only partly successful hemodynamically, these “homograft valves” had remarkable durability and performance. Some patients had no calcification or transvalvular gradients for up to 20 years, whereas others ultimately failed as a consequence of progressive fibrosis and calcification.2,3⇓ In 1962, the initial use of aortic valve homografts in the orthotopic position were reported independently by Sir Donald Ross of England and Sir Brian Barrett-Boyes of New Zealand.4–6⇓⇓ As manufactured prosthetic valves gradually evolved in design and range of choices, homograft use began to decline because of issues of acquisitional logistics, banking, transport, sizing, infectious disease transmission, and others. With the development of organized organ and tissue donation for transplantation in the 1980s and 1990s, cardiovascular allograft tissues became increasingly available primarily as cryopreserved valves with variably retained native cell viability. Importantly, the terrific surgical and specific performance advantages of allograft semilunar cardiac valves have been recognized by reconstructive surgeons worldwide.7 These valve “transplants” have by and large crossed histocompatibility and ABO constraints, however. Although they perform well in the short- to mid-term, they have been associated with ultimate fibrosis and failure in a significant proportion of cases, especially in patients for whom the desirability of a living transplant would be the greatest: neonates, infants, and young children (ie, for whom retained growth and repair functions would be ideal). Thus, there have been many attempts to modify homograft valve transplants at either the donor or recipient level to achieve relative or actual immune …

Six-year monitoring of the donor-specific immune response to cryopreserved aortic allograft valves: Implications with valve dysfunction

Background The immune rejection has been anticipated as one of the major causes of allograft aortic valve (AAV) degeneration. The purpose of this study was to prospectively serially measure the magnitude and evolution of the recipient anti-HLA class I antibody response up to 6 years from AAV implant and to correlate serologic data with valve performance by means of a concurrent echocardiographic survey. Methods Cryopreserved AAVs were obtained from multiorgan HLA-typed donors. Nineteen patients younger than 50 years (mean age, 43.3 ± 8 years) were prospectively studied. After successful surgery, all AAV recipient underwent at 3 and 6 months and each year postoperatively (mean follow-up, 71.9 months) concomitant serum sample collection and two-dimensional transthoracic echocardiography. The presence of anti-HLA antibodies was tested against a panel of lymphocytes obtained from 30 blood donors. Results Progressive structural valve deterioration was seen in 6 patients (31.5%) of whom 4 (21%) were reoperated. All pretransplant recipients sera were panel-reactive antibody negative. Seventeen patients (89.4%) demonstrated significant panel-reactive antibody levels, which peaked at 6 months postoperatively, declined from 6 to 24 months, and slowly decreased afterward. In 14 of 19 cases (73.6%) donor-specific HLA antibodies were identified. A strong immunization (6-year persistence of panel-reactive antibody > 70% and peak panel-reactive antibody > 80%) was detected in 31.5% and 36.8% of recipients, respectively. Strong immunization was found to be significantly associated with progressive structural deterioration. Conclusions The immune reaction after cryopreserved AAV implantation is a peculiar long-lasting response occurring in the majority of recipients younger than 50 years of age. An association between a sustained and pronounced immunization and an aggressive AAV degeneration was observed.

Invited commentary

Invited commentary

Untreated tetralogy of Fallot in an adult patient complicated by acute aortic valve endocarditis

Acute endocarditis complicated by aortic valve regurgitation is an uncommon finding in adults with surgical untreated tetralogy of Fallot (TOF). The hemodynamic consequences for both, the right and left ventricles, are significant. However, the right ventricle may be in a disastrous situation, since a compromised right ventricle from longstanding pressure overload may not tolerate acute volume overload. Here we report a 28-year-old African adult patient with TOF and acute severe aortic valve regurgitation due to bacterial endocarditis with preoperative low cardiac output syndrome. After aortotomy a large abscess cavity underneath the left and non-coronary sinus and a TOF typical perimembranous ventricular septal defect (VSD) were visible. Autologous glutaraldehyde-treated pericardium was used to reconstruct the aortic-mitral curtain. For repair of the TOF a vertical incision in the right ventricular outflow tract was performed and the infundibular septum was resected. The perimembranous VSD was closed with glutaraldehyde-fixed autologous pericardium, whereas the cranial part of the patch formed the aortic annulus. An aortic homograft was implanted as a full aortic root. The patient recovered early and uneventful. Adult TOF may be complicated by acute aortic valve endocarditis with emergent surgical intervention. Homograft aortic valve replacement is feasible in this setting.