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In this investigation, we hypothesize that quality of oral anticoagulation (OA) and long-term outcome after mechanical heart valve (MHV) replacement with self-management (Self-M) of OA is superior to conventional anticoagulation treatment (Conv-T), even in outside trial conditions. One hundred sixty patients (78.8% aortic valve replacements) were trained in international normalized ratio Self-M and 260 patients (86.2% aortic valve replacements) preferred Conv-T. Mean follow-up was 8.6 ± 2.1 years, representing 3612 patient-years. During follow-up, 37.2% bleedings and 10.6% thromboembolic events were recorded in the Self-M group versus 39.6% bleedings (P = 0.213) and 15.4% thromboembolic events (P = 0.064) in the Conv-T group. Serious adverse events were significantly lower in the Self-M group [grade III bleeding events causing disability or death: 0 versus 4.6% (P = 0.03); grade III thromboembolic events: 0.6 versus 5.0% (P = 0.011)]. Patients with Self-M were significantly more satisfied with their OA management and their quality of life (P

Background Calcineurin-inhibitor-(CNI)-induced renal failure is one major cause of morbidity in cardiac transplantation (HTx). In this prospective, randomized, multicenter trial, the impact of immunosuppressive conversion toward CNI-free (mycophenolate mofetil [MMF] and sirolimus) or a CNI-reduced immunosuppressive regimen on renal function, efficacy, and safety was evaluated. Methods Since 2004, 63 HTx-patients (0.5-18.4 years after HTx) with CNI-based immunosuppression and reduced creatinine clearance less than 60 mL/min (39+/-15 mL/min) were included in this trial. Patients in the CNI-free-Group (group 1) were converted to sirolimus that was started with 2 mg/day until target trough levels (8-14 ng/mL) were achieved. Subsequently, CNIs were withdrawn. In CNI-reduction-Group (group 2), CNI target trough levels were reduced by 40%. In both groups MMF was continued and trough level adjusted (1.5-4 microg/mL). Results Patients demographics and survival (mean follow-up time: 16.7+/-9 months) was equal (100%). Renal function improved significantly after complete CNI withdrawal while remaining unchanged with CNI-reduction (Creatinine clearance after 12 months: 53+/-24 mg/dL [group 1] vs. 38+/-20 mg/dL [group 2], P=0.01). End-stage renal failure (hemodialysis) was avoided by CNI-withdrawal and occurred only after CNI reduction (n=6; P=0.01). Acute rejection episodes were more common in group 2 (4 vs. 2). Graft function remained stable (echocardiography) within both groups. Adverse events were more common in group 1 (65%) than in group 2 (n=40%) and were responsible for discontinuation in 4 and 0 cases, respectively. Conclusions Conversion toward a CNI-free immunosuppression (Mycophenolate, sirolimus) is superior to CNI-reduced immunosuppression in improving renal failure in late HTx-recipients. However, this benefit is relativized by the increased incidence and severity of sirolimus/MMF-associated side effects.

Current techniques to resolve heart valve defects involve the use of prosthetic and bioprosthetic materials. These materials lack the potential to grow and are not ideal, especially not for pediatric patients. Novel techniques like tissue engineering involve the use of biodegradable polymers coated with autologous myofibroblast and endothelial cells. We inspected morphological and marker gene expression differences between cells harvested from the saphenous vein, or from veins and arteries of the umbilical cord, and the cells they are designed to replace: the interstitial and endothelial cells of the pulmonary heart valve. We assessed the extent to which the endothelial cells from the inspected sources in vitro resemble endothelial cells of human pulmonary heart valves, and we found that myofibroblast cells, respective of their source, in vitro differ from the interstitial cells from human pulmonary heart valves regarding collagen and smooth muscle alpha-actin. Therefore we conclude that the cells isolated from the saphenous veins, or from veins and arteries of the umbilical cord might be feasible cell sources for tissue engineering of heart valve for the pulmonary position.

Background: Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)-based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. Methods: Since 1999, 12 HTx recipients (10 men; 58 ± 3.6 yr of age; 8.7 ± 4.2 yr after HTx) with CNI-based immunosuppression and a calculated creatinine clearance (CreaCl)

Background Stenoses of venous grafts represent a major limitation in coronary artery bypass surgery. The use of viral vectors to facilitate over-expression of factors within the graft to promote long-term patency is a promising new therapeutic concept. One of the viral vector systems is the adeno-associated virus (AAV); a non-pathogenic single stranded DNA virus, which elicits only low immunological responses. Methods and Results Recombinant AAV vector coding for β-galactosidase was produced and transferred ex vivo using intraluminal application to previously harvested rabbit internal jugular vein grafts (n=8). The 30 min after application, an end-to-end anastomosis of each graft as a bypass to the carotid artery was performed in a previously established rabbit bypass model. X-Gal-staining of the grafts was performed after killing the animals to quantify gene expression. AAV transduction was successful in 100% of the grafts. After 30 days, β-galactosidase gene expression could be assessed in the medial layer of the graft. Furthermore, no signs of inflammation could be detected. Conclusions These findings suggest that recombinant AAV vectors are an alternative to the widely used adenoviral based vectors. These data support the further use of AAV vectors to overcome intimal hyperplasia after vein graft coronary artery bypass surgery. (Circ J 2008; 72: 1700 - 1704)

Donor organ shortage in pediatric heart transplantation (HTx) is causing mortality rates of 30-50% on the waiting list. Due to immaturity of the immune system of newborns and infants, ABO-incompatible HTx may be an option to increase donor availability. We present our experience with ABO-incompatible HTx.Three infants were transplanted ABO-incompatible since 12/2004: (1) hypoplastic left heart complex, (2) restrictive hypertrophic cardiomyopathy, (3) dilative cardiomyopathy. Age at HTx was 7, 5, and 3.5 months. All recipients had blood type O, donors were A, A, and B. Informed consent was given by parents, the ethics committee, and Eurotransplant.Preoperative isohemagglutinin titers were low (Patient 1: 1:4 for anti-A1, A2, B, Patient 2: 1:4, 1:1, 1:4 for anti-A1, A2, B, respectively, and Patient 3: 0 for all, but quick spin 1+ for all). Intraoperatively, plasma was separated from red blood cells and discarded up to six times until antibodies were eliminated. Immunosuppressive induction with ATG was started for 5 days. Basic immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Extubation was performed on days 15, 2, and 1, respectively. After a follow-up of 17, 16, and 12 months all patients are well, ventricular function is excellent without any acute rejection periods; Patient 1 is still on dialysis. Isohemagglutinin titers against donor blood type have disappeared in follow-up.ABO-incompatible cardiac transplantation shows good short-term results in young infants and seems to be a safe procedure to lower the mortality on the waiting list.

HLA matching has improved outcome in kidney transplantation but is not considered in current allocation policies in heart transplantation. The aim of this single-center study was to assess the impact of HLA matching on long- term outcome after heart transplantation.The records of 240 consecutive heart transplant recipients (time period 1995 to 2002; mean age 51.8 +/- 11.7 years; mean follow-up 5.9 +/- 1.8 years) were analyzed retrospectively. According to the renal allocation policy, HLA mismatches (MM) on the major antigen loci HLA-A, HLA-B and HLA-DR were calculated, demonstrating 0 to 6 MM. Patients with primary graft failure were excluded from statistical analysis.Survival analysis revealed a statistically significant impact of HLA-DR MM on survival. Five-year survival was 90% in patients without HLA-DR MM (n = 10), 79% in patients with 1 HLA-DR MM (n = 113), and 68.1% in patients with 2 HLA-DR MM (n = 117) (1 MM vs 2 MM: p0.05). Freedom from cardiac allograft vasculopathy after 5 years was 89% in HLA-DR-identical recipients (n = 10), 61% in patients with 1 HLA-DR MM (n = 102), 54% in patients with 2 HLA-DR MM (n = 104). Conventional matching with 6 mismatches over the three major HLA antigen loci revealed a trend toward a higher relative risk for adverse outcome in patients with increased MM.HLA-DR matching had a significant impact on survival after heart transplantation (HTx) at our center. In the effort to achieve the best comparative use of scarce donor organs the inclusion of HLA-DR matching into allocation policies might improve long-term outcome after HTx.

Background The impact of long-term mycophenolate mofetil (MMF) treatment on the development of cardiac allograft vasculopathy (CAV) after heart transplantation is an area of much recent interest. This study analyzed the effects of various immunosuppressive combinations, including cyclosporine (CsA), azathioprine (Aza), tacrolimus (Tac) and MMF, on the time of onset, extent and progression of CAV. Methods Two hundred seventy-three consecutive heart transplant recipients (mean age: 51.2 ± 12.2 years; mean follow-up: 6.8 ± 1.9 years) were examined by coronary angiography on a yearly basis between 1995 and 2003. The extent of CAV was evaluated using a scoring system based on the severity of vessel stenosis. The onset of CAV was analyzed using Kaplan–Meier estimates and the log rank test for four treatment combinations, CsA/Aza ( n = 47, 17.2%), CsA/MMF ( n = 26, 9.5%), Tac/Aza ( n = 62, 22.7%) and Tac/MMF ( n = 138, 50.5%), and for the primary and the secondary immunosuppressants alone. Results The rate of freedom from CAV at 5 years was 47% with CsA/Aza, 66% with CsA/MMF, 60% with Tac/Aza and 70% with Tac/MMF. After 5 years, the Tac/MMF group showed a significantly lower incidence of CAV than the CsA/Aza group (log rank 7.58, p = 0.0059). CsA ( n = 73) was compared with Tac ( n = 200) and MMF ( n = 164) with Aza ( n = 109): the rate of freedom from CAV was 51.2% in CsA patients vs 66.1% in Tac patients (log rank 5.7, p = 0.017), and 54.6% in Aza patients vs 67% in MMF patients (log rank 4.36, p = 0.037). Multivariate Cox regression analysis revealed that MMF decreased the incidence of CAV significantly ( p = 0.041). In this patient cohort, Tac or CsA medication was not an independent risk factor for incidence of CAV nor for decreased survival. Conclusions The choice of immunosuppression has an impact on the incidence of CAV. In terms of prevention of CAV, MMF is superior to Aza in either combination. A trend toward improved survival in MMF patients was noted. The lower number of rejection episodes in the MMF groups may have contributed to these results.

Background In end-stage cardiomyopathy where concomitant chronic renal failure is a contraindication for cardiac transplantation (HTx), simultaneous heart and kidney transplantation (HKTx) may be the only feasible therapeutic option. Due to the increased donor shortage, the clinical outcome of combined HKTx patients on tacrolimus-based immunosuppression was assessed and compared with a group of HTx patients. Methods Three hundred forty-nine HTxs, including 13 (4%) combined HKTxs, were performed since 1995. Two hundred twenty-one HTx and all HKTx recipients received tacrolimus-based immunosuppression. Acute rejection episodes (AREs), infections, renal function and clinical outcome were evaluated. Pre-operative renal diagnoses for HKTx patients included cystic nephropathy ( n = 4), glomerulonephritis ( n = 4), cytostatica-induced nephropathy ( n = 1), chronic rejection after renal transplant ( n = 1), reflux nephropathy ( n = 2) and chronic calcineurin-inhibitor –induced nephropathy after HTx ( n = 1). Twelve patients (92%) were on hemodialysis pre-operatively, 1 underwent implantation of a left ventricular assist device (LVAD) before HKTx. Results After 4.7 ± 2 years, 92% of HKTx compared with 85% of HTx patients had survived ( p = 0.42). Acute cardiac rejection episodes were more frequent in HTx than in HKTx patients (0.04 ± 0.09 vs 0.02 ± 0.04 ARE/100 patient-days; p = 0.07). Incidence of infection was comparable (0.3 ± 0.2 vs 0.5 ± 0.4 infection/100 patient-days). Freedom from transplant vasculopathy was 100% in the HKTx group compared with 71% in the HTx group after 4 years ( p = 0.04). Conclusions Tacrolimus-based immunosuppression yields promising long-term results in HKTx and HTx. The incidence of transplant vasculopathy seems to be lower after HKTx than after HTx. If these results are secondary to a protective effect of tacrolimus-induced tolerance or of tolerance-associated co-transplantation they will need to be investigated in prospective multicenter trials.

Advanced recipient age is considered a relative contraindication for heart transplantation because it might be associated with increased morbidity and mortality. We analyzed 349 consecutive heart transplantations performed at our institution from 1995 to 2002 (n = 349, mean follow-up 3.5 +/- 2.5 years). The survival rate was lower in older recipients. Less chronic rejection but increased risk for infectious complications, renal failure and neoplasms indicate the need for decreased immunosuppression and effective infection prophylaxis in older recipients.

INTRODUCTION The purpose of this study was to evaluate the effect of different adaptation phases on the shear-stress resistance of endothelial cells seeded artificially onto vascular prostheses and biological heart valves. MATERIAL AND METHODS Human endothelial cells (EC), fibroblasts (FB), and smooth muscle cells (SMC) were isolated from vena saphena magna pieces and expanded in culture. Group A: 15 polyurethane vascular grafts (20 mm diameter) were seeded with FB and SMC (53 +/- 1.2 million cells), followed by EC seeding (39 +/- 0.9 million cells). Group B: eight stentless porcine valves (Freestyle, Medtronic, USA) were seeded with FB (68 +/- 1.5 million cells) and EC (42 +/- 1.1 million cells). Shear-stress testing was done under pulsatile flow (pulse rate: 80 pulses/min.). Adaptation phase: flow was set to 0.9 +/- 0.3 l/min (systolic pressure: 40 - 50 mm Hg). High flow was 3.2 +/- 0.6 l/min. (systolic pressure: 140 - 160 mm Hg) and lasted over four hours in all groups. The vascular grafts were divided into three groups (n = 5 each): group 1 (high flow immediately), group 2 (adaptation phase of 15 minutes), and group 3 (adaptation phase of 30 minutes). The valves either were given high flow immediately (n = 4) or had an adaptation phase of 30 minutes (n = 4). Specimens were obtained after cell seeding, before, and after perfusion. RESULTS A confluent EC layer was achieved on all grafts. After perfusion without adaptation, large defects within the cell layer were found. No FB and SMC were seen at the bottom of these defects. In group B, the defects were largest on the ventricular surface of the leaflets. After an adaptation phase of 15 minutes in group A, only a few defects within the EC layer were detected with a still confluent FB and SMC. After a 30-minute adaptation phase defects within the EC layer were very rare and no interruption of the underlying FB and SMC layer was seen. Immunohistochemical staining for factor VIII and CD31 proved the EC to be viable and staining for collagen IV and laminin revealed the formation of a basement membrane. After perfusion, the specimen also stained positive for eNOS. CONCLUSION An adaptation phase of 30 minutes proved to be sufficient to allow artificially seeded endothelial cells to adapt to shear stress. The formation of a basement membrane was of great importance for the maintenance of a confluent EC layer.

Objective: Current prosthetic heart valves necessitate permanent anticoagulation or have limited durability and impaired hemodynamic performance compared to natural valves. Recently a polymeric valve prostheses with special design for mitral position demonstrated excellent in vitro and in vivo results with improved durability and no need for permanent anticoagulation. In this study, a respective flexible polymeric aortic valve is presented and in vitro and in vivo results are reported. Methods: The aortic prosthesis (ADIAM® lifescience AG, Erkelenz, Germany) is entirely made of polycarbonaturethane. The tri-leaflet flexible prosthesis mimicks the natural aortic valve and has a diminished pressure loss and reduced stress and strain peaks at the commissures. The valve underwent long-term in vitro testing and in vivo-testing in a growing calve animal model (20 weeks, 7 aortic valves) and was compared to two different commercial bioprostheses. Results: The polymeric aortic heart valve substitute demonstrated excellent in vitro and in vivo hemodynamics. Five/seven animals with aortic PCU-prostheses had an excellent clinical long-term course. The explanted valves showed a variable degree of calcification. Two of the seven animals died at 27 and 77 days due to pannus overgrowth causing severe LVOTO without degeneration of the valve itself. Both animals with commercial bioprostheses had to be sacrificed because of congestive heart failure related to structural degeneration of the bioprosthesis after 10 and 30 days of implantation. There was no increased thrombogenity of the PCU valves compared to bioprostheses. Conclusion: The new flexible polymeric aortic valve prosthesis is superior to current bioprostheses in animal testing.

Objective: Calcineurin inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this prospective study was to evaluate the safety and efficacy of a completely CNI-free immunosuppressive regimen [mycophenolate mofetil (MMF) and sirolimus (Sir)] in HTx-recipients with late post-transplant renal impairment. Methods: Since 2001, 30 HTx-patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine > 1.9 mg/dl were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Conversion was started with 6 mg Sir or 500 mg MMF according to the pre-existing regimen and was continued with the dose adjusted to achieve target trough levels between 8 and 14 ng/ml (Sir) or 1.5 and 4 μg/ml (mycophenolate). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up included endomyocardial biopsies, echocardiography and laboratory studies. Additionally, every HTx-patient treated at our centre between 1996 and 2001 due to chronic renal failure without immunosuppressive conversion and fulfilling the inclusion criteria were retrospectively analysed and acted as control group. Results: Patient demographics and 1-year survival [93 (conversion) vs 90% (control)] were compared. No acute rejection episode was detected in either group. Renal function improved significantly in the conversion group (creatinine: 3.18 ± 0.71 vs 2.22 ± 0.79 mg/dl, P = 0.001; cystatin pre- vs post-conversion: 2.95 ± 1.06 vs 2.02 ± 1.1 mg/l, P = 0.01). In three patients haemodialysis therapy was stopped completely after conversion. In the control group renal impairment was deteriorating, creatinine increased from 2.44 ± 0.8 to 3.28 ± 1 mg/dl (P = 0.01). In 10 out of 33 patients chronic haemodialysis had to be initiated within 1 year. Although side effects of CNI-free immunosuppression were common (76%), no patient had to be excluded due to adverse effects. Conclusions: Conversion from CNI-based immunosuppression to MMF and Sir in HTx-patients with chronic renal failure was safe, preserved graft function and improved renal function.

Repair of complete atrio-ventricular septal defect (AVSD) remains a challenging procedure due to the complex three-dimensional malformation of the septa and the AV-valves and variable anatomy. Different techniques for correction have been applied with comparable results. In this article, the pathological anatomy of complete AVSD and surgical repair with the two-patch technique are described in detail. Special regard is given to correction avoiding damage to the conduction system and to complete closure of the mitral valve cleft. Finally, our own results are reported.

INTRODUCTION: Skeletal myoblasts have been shown to survive transfer into myocardial scar tissue. The purpose of this study was to investigate differentiation after intramyocardial transplantation. Additionally, we evaluated an intravital fluorescence dye. MATERIALS AND METHODS: Skeletal myoblasts were harvested from 8 male inbred Lewis rats and expanded in culture. For each transplantation planned, 10(6) cells were trypsinized and incubated for three minutes with 2 ml of buffered PKH-26 solution (Sigma, St. Louis). This dye was integrated into the cell membrane. After washing three times, the cells were plated again for two more days. The cells were then transplanted into the hearts of 60 female Lewis-rats, mean weight 380 g (260 - 450 g). At implantation, 10(6) cells suspended in 100 microliters were injected into the apex region of the left ventricle. 12 animals served as the control group with only cell medium injected. Animals were sacrificed after 1, 2, 6, 8, 12, and 16 weeks (n = 10 each). The hearts were explanted and serial frozen sections of the hearts were prepared for detecting labeled cells. Sections with labeled cells were stained immunohistochemically for Myo D1 (myogenic origin), n-cam (early myotubes), desmin (muscular filament), myosin light chain (muscular contractile protein), and connexin 43 (tight junction). RESULTS: Cell labeling was successful in all cases. After two days, the myoblasts had recovered from the staining procedure. The fluorescing dye, however, was only rarely transmitted by cell division. Marked cells were found in the intercellular spaces between the cardiac myofibers in at least 8 animals from each group. No fibrotic reaction or inflammation was seen surrounding the transplanted cells. Up to 6 weeks after implantation, the cells stained positive for n-cam and Myo D1, and particularly for desmin. More n-cam positive cells were found than labeled cells, indicating cell division after the cell transfer. Two animals suffered sudden death after a follow-up time of 8 and 10 weeks, which was possibly due to cardiac arrhythmia. After 8 weeks, the cells formed conglomerates and stained positive for desmin, myosin light chain, and connexin 43. The cells were not structurally integrated into the recipient myocardial tissue, however. CONCLUSIONS: Myoblasts divided further after transplantation into rat myocardium. Positive staining for desmin demonstrated the development of myofibers. Starting at 8 weeks after transplantation, the cells started differentiation without reaching structural integration during follow-up. Labeling the cells with PKH-26 proved to be a reliable method to detect the cells.

OBJECTIVE Allocation criteria changed in 2000 as a result of Germany's new transplantation law. Before, thoracic organs were primarily allocated electively within the donor region (according to urgency and waiting time). Afterwards, all patients in Germany eligible for heart transplants were registered in a national waiting list. With the exception of high-urgency patients that are approved by an audit committee, waiting time has become the major criteria for allocation. In this study, we investigated the impact of the new allocation system on economic aspects as on clinical results. METHODS One year in the new allocation system (NA) was compared to the previous year in the old allocation system (OA) regarding explantation/transportation distance, costs, ischemia time and clinical outcome. All explantations performed by our institution within Germany were evaluated. RESULTS The number of transplantations and the spectrum was similar between the two time periods (NA vs. OA: 61 vs. 57 overall). Eighty-two percent of these explanted organs were transplanted within the donor region in the OA time period, but only 37 % in the NA period. This resulted in higher transportation distances (NA: 441 +/- 177 km vs. OA: 179 +/- 118 km), higher transportation cost (NA: EUR 4,472 +/- 2,858 per explantation vs. OA: EUR 1,858 +/- 2,293 explantation, p = 0.001), and therefore longer ischemia times in the NA period (NA: 264 +/- 56 min: OA: 208 + 61 min, p = 0.001). Perioperative results and survival after a mean clinical follow-up of 21 +/- 8 (OA) and 11 +/- 5 (NA) months were comparable (86 % vs. 87 % (p = 0.93). CONCLUSION Transportation distance, costs for explantation and ischemia time increased significantly with the NA period. While the clinical short-term outcome proved to be comparable, we cannot yet judge the long-term impact of the prolonged ischemia time on the development of chronic rejection.

Background . Patients with absent pulmonary valve syndrome (APVS) with respiratory distress (RD) have previously had a high mortality. In 1990 we adopted a strategy of primary repair including total replacement of the aneurysmal central pulmonary arteries (PAs) for patients with RD. Methods . Retrospective review was made of 54 consecutive patients with APVS between 1960 and 1998. Median age and weight were 4 months and 4.8 kg. RD was present in 23 patients (10 neonates, 16 required ventilation). Fifteen patients had repair with homograft replacement of the PAs and VSD closure (group 1). Twenty-seven patients had transannular patch with VSD closure with PA-plasty (group 2, n=21) or without PA plasty (group 3, n=6). Twelve had miscellaneous procedures (group 4); in 6 the VSD was left open. Results . Operative, 1-, 5-, and 10-year survivals were 83%, 80%, 78%, and 78%, respectively. Risk factors for operative mortality in multivariate analysis were RD ( p = 0.04), neonates ( p = 0.02), weight less than 3 kg ( p = 0.02), open VSD ( p = 0.02) and surgery before 1990 ( p = 0.04). Since 1990 operative mortality has decreased to 11% ( p = 0.04). RD was the only time-related predictor of survival in multivariate analysis ( p = 0.004). In patients with RD, survival with homograft was 73% versus 41% with other techniques ( p = 0.2). Mean follow-up was 72 ± 50 months. There were no significant differences in freedom from reintervention rates among the surgical groups ( p = 0.08). Conclusions . Aggressive homograft replacement of the central pulmonary arteries has been associated with improved survival in patients with APVS especially in neonates with severe RD.

BACKGROUND To evaluate the impact of intramural coronary arteries for the peri-, postoperative and long-term course after arterial switch operation (ASO). METHODS ASO was performed in 351 patients between 1981 and 2000 with dextrotransposition of the great arteries (d-TGA). Five patients (1.4 %) had an intramural coronary artery. Coronary transfer was performed with a collar under dissection of the commissure without longitudinal splitting of the intramural section. RESULTS None of these patients died; the intraoperative course was uneventful, and no myocardial ischemic changes were observed. In three patients, follow-up cardiac catheterization after 5, 16 and 53 months revealed an occlusion of the intramural coronary ostium. Exercise electrocardiography and myocardial scintiscan showed myocardial ischemia. Two of these patients underwent a successful internal mammary artery bypass. CONCLUSIONS The intramural course of coronary arteries in patients with d-TGA is rare and does not cause increased mortality or myocardial infarction rates. However, the risk of coronary occlusion over time seems to be high. Therefore, patients with this condition require selective coronary angiography and frequent exercise investigations. Revascularization with an internal mammary artery bypass may be indicated.

UNLABELLED Postoperative measurement of cardiac troponin I, creatine kinase and procalcitonin reflects myocardial damage and systemic inflammatory response after cardiac surgery with cardiopulmonary bypass in children. Pulse-contour cardiac output technique is a less invasive tool for determining postoperative cardiac function. OBJECTIVE The aim of our study was to investigate myocardial lesions and systemic inflammatory response after cardiac surgery with cardiopulmonary bypass in children suffering from congenital heart defects. METHODS The elevation of cardiac troponin I (cTnI), creatine kinase (CK) and procalcitonin (PCT) was evaluated in relationship to duration of aortic cross-clamping, incisional trauma and cardiac bypass temperature in 37 paediatric patients. To assess postoperative cardiac function, the cardiac index was measured in 7 children using the PiCCO (pulse contour cardiac output) technique. RESULTS CTnI and PCT both peaked on the day of surgery and slowly decreased postoperatively in case of an uncomplicated course. The median values of both parameters differed significantly from the day of surgery until the fourth postoperative day in children with an aortic cross-clamping time (CCT) longer than 80 minutes or after ventriculotomy in comparison to patients with shorter clamping times or atriotomy only. CK values showed similar results, but were less significant than cTnI. A relationship between cTnI, CK or PCT and the body temperature during cardiopulmonary bypass was not found. The cardiac indices (CI) measured by the PiCCO technique in the first 48 hours after surgery showed normal values. CONCLUSION In summary, perioperative measurement of cTnI, CK and PCT reflects myocardial damage and systemic inflammatory response and allows an improved peri- and postoperative management. PiCCO technique is an excellent, less invasive tool to determine postoperative cardiac function.

Background . Failure of the systemic right ventricle after atrial switch operation can be treated by conversion into an arterial switch operation. Methods . Four patients, age 38 to 59 months, presented with right ventricular failure after Senning operation and ventricular septal defect closure. One patient had elevated left ventricular pressure; in the other three patients the left ventricle was retrained to a left ventricular/right ventricular pressure ratio of 0.8 or greater by pulmonary artery banding in 12 to 24 months. Results . Postoperative course after arterial switch operation was prolonged, but clinical condition was good at discharge. Fractional shortening ranged from 20% to 28%. Trace-to-moderate aortic regurgitation was present; only 1 patient had preserved sinus rhythm. After a mean follow-up of 43.5 months 1 patient had died due to left ventricular dysfunction. The survivors are in New York Heart Association functional class I to II. Fractional shortening has improved (29% to 37%); aortic regurgitation has not increased. No patient has undisturbed sinus rhythm. Conclusions . Conversion of an atrial into an arterial switch is an alternative to cardiac transplantation in childhood. However, the procedure is demanding. Long-term morbidity is caused by rhythm disturbances. Aortic valve performance and left ventricular function require close observation.

Background . Tissue engineering is a new approach, whereby techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional tissue in vitro and in vivo. Our laboratory has focused on the tissue engineering of heart valves, and we have fabricated a trileaflet heart valve scaffold from a biodegradable polymer, a polyhydroxyalkanoate. In this experiment we evaluated the suitability of this scaffold material as well as in vitro conditioning to create viable tissue for tissue engineering of a trileaflet heart valve. Methods . We constructed a biodegradable and biocompatible trileaflet heart valve scaffold from a porous polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted of a cylindrical stent (1 × 15 × 20 mm inner diameter) and leaflets (0.3 mm thick), which were attached to the stent by thermal processing techniques. The porous heart valve scaffold (pore size 100 to 240 μm) was seeded with vascular cells grown and expanded from an ovine carotid artery and placed into a pulsatile flow bioreactor for 1, 4, and 8 days. Analysis of the engineered tissue included biochemical examination, enviromental scanning electron microscopy, and histology. Results . It was possible to create a trileaflet heart valve scaffold from polyhydroxyalkanoate, which opened and closed synchronously in a pulsatile flow bioreactor. The cells grew into the pores and formed a confluent layer after incubation and pulsatile flow exposure. The cells were mostly viable and formed connective tissue between the inside and the outside of the porous heart valve scaffold. Additionally, we demonstrated cell proliferation (DNA assay) and the capacity to generate collagen as measured by hydroxyproline assay and movat-stained glycosaminoglycans under in vitro pulsatile flow conditions. Conclusions . Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart valve scaffold. The cells appear to be viable and extracellular matrix formation was induced after pulsatile flow exposure.

Objective: We compared the Norwood stage I operation for hypoplastic left heart syndrome and other complex malformations with ductus-dependent systemic circulation. Methods: A retrospective study of 194 patients who underwent a Norwood stage I palliation between 1990 and 1998 was conducted. Malformations in 131 patients were classified as hypoplastic left heart syndrome, defined as aortic and mitral atresia or severe stenosis, normal segmental anatomy, intact ventricular septum, and hypoplasia of the left ventricle. Sixtythree patients had other lesions: hypoplastic left ventricle with ventricular septal defect (n = 18), unbalanced complete atrioventricular canal (n = 9), complex double-outlet right ventricle (n = 14), double-inlet left ventricle (n = 11), tricuspid atresia with transposition of the great arteries (n = 6), and others (n = 5), including heterotaxia. Results: Operative (>30 days) and 1-year survivals were lower for patients with hypoplastic left heart syndrome than for those with other lesions (63.4% vs 81%, P = .008, and 51.2% vs 71.4%, P = .02, respectively). The presence of a nonhypoplastic left ventricle (n = 27) was associated with higher operative and 1-year survivals (96.3% vs 64.7%, P = .002; 88.9% vs 52.7%, P < .001). A restrictive atrial septal defect and prematurity tended to increase mortality across both groups. Cox proportional hazards regression indicated that a single right ventricle was the most important independent predictor of death (P < .001). Operative mortality for all patients undergoing the stage I procedure decreased from 38.5% (1990-1994) to 21.4% after 1994 (P = .02). Conclusions: The survival of patients with malformations other than hypoplastic left heart syndrome after the Norwood procedure is greater than for those with hypoplastic left heart syndrome. Staged palliation is valid surgical therapy in these patients, with good results in intermediate follow-up. (J Thorac Cardiovasc Surg 2000; 119:358-67)

Surgical management of common atrioventricular (AV) canal has evolved significantly since original descriptions of repairs in 1955. Currently, complete repair is performed in infancy in most forms of complete AV canal with low mortality and morbidity. Various modifications to the original surgical techniques have been proposed and are utilized to close the inter-atrial and inter-ventricular communications, and achieve a competent AV valve. The two most commonly used techniques (single and double patch) are described in detail along with our approach to the management of the AV valves. Associated defects such as coarctation of the aorta, tetralogy of Fallot, transposition of the great arteries, and unusual left AV valve anatomy are discussed. Management of unbalanced forms of AV canal and criteria for deciding adequacy of cavity size for two-ventricle repair remains an area of some controversy and is still evolving. Our experience with common AV canal from 1990 to the end of 1998 covers 365 patients who underwent two-ventricle repair at a median age of 4.6 months. Early mortality for complete AV canal patients was 1.5%, and 10% of these had at least moderate left AV valve regurgitation post-operatively. Eighteen patients have required re-operation for severe mitral valve regurgitation at a mean of 20 months after the original repair and three others for sub-aortic obstruction. Our current management of children with complete common AV canal is to perform corrective surgery electively early in infancy, within the first 4–6 months of life. Symptomatic infants with signs of congestive heart failure should undergo repair as soon as symptoms are apparent.

We report a rare case of a successful cardiac transplantation in a patient suffering from cardiomyopathy and complex mitochondrial disease. The patient presented with severe heart failure and malignant ventricular arrhythmias requiring implantation of a defibrillator and advanced medical treatment. The patient was listed for urgent heart transplantation and received a donor heart after 36 days. One yr post-operatively, the patient has completely recovered.

We present a case of partial Cantrell's syndrome with ventricular septal defect, left ventricular diverticulum, dextrorotation of the heart, an anterior diaphragmatic defect, and a midline supraumbilical abdominal wall defect with omphalocele. At the age of 20 months, the patient underwent a successful cardiac surgical procedure. To detect risk factors and to define therapeutic strategies, we analyzed the spectrum and the frequency of malformations described in 153 patients with Cantrell's syndrome. Despite modern surgical standards, Cantrell's syndrome represents a challenge to the surgeon because of the wide spectrum of anomalies, the severity of the abdominal and cardiac malformations, and the high mortality.

Background Tissue engineering of autologous heart valves with the potential to grow and to remodel represents a promising concept. Here we describe the use of cryopreserved umbilical cord blood-derived CD133 + cells as a single cell source for the tissue engineering of heart valves. Methods After expansion and differentiation of CD133 + cells, phenotypes were analyzed by immunohistochemistry and cryopreserved. Heart valve scaffolds fabricated from a biodegradable polymer (n = 8) were seeded with blood-derived myofibroblasts and subsequently coated with blood-derived endothelial cells. Afterward, the heart valve constructs were grown in a pulse duplicator system. Analysis of all heart valves, including histology, immunohistochemistry, electron microscopy, fluorescence imaging, and biochemical and biomechanical examination, was performed. Results The tissue-engineered heart valves showed endothelialized layered tissue formation including connective tissue between the inside and the outside of the scaffold. The notion of an intact endothelial phenotype was substantiated by fluorescence imaging studies of cellular nitric oxide production and Ca 2+ signaling. Electron microscopy showed that the cells had grown into the pores and formed a confluent tissue layer. Biochemical examination showed extracellular matrix formation (77% ± 9% collagen of human pulmonary leaflet tissue [HPLT], 85% ± 61% glycosaminoglycans of HPLT and 67% ± 17% elastin of HPLT). Conclusions Importantly, this study demonstrates in vitro generation of viable human heart valves based on CD133 + cells derived from umbilical cord blood. These findings constitute a significant step forward in the development of new clinical strategies for the treatment of congenital defects.

Orthotopic heart transplantation is definitive therapy for infants with failing staged palliation after univentricular repair. Although the surgical management of these patients may be quite straightforward, the actual cardiac and vascular anatomy is sometimes unpredictable. To overcome this problem, we developed a new technique to fabricate a custom made replica from 128-slice computed tomographic (CT) and magnetic resonance imaging (MRI) angiography to create a realistic model of the anatomic situation for preoperative assessment and intraoperative orientation in 2 patients with failed staged palliation. In such situations, solid replicas may be helpful in choosing surgical treatment strategies before heart transplantation, for intraoperative orientation, and in demonstrating the planned procedure to patients and parents with lifelike models.

Introduction Although amphotericin was the gold standard in the treatment of invasive aspergillosis in transplant recipients, nephrotoxicity and lack of efficacy often limits its use. Itraconazole is better tolerated but less efficacious and influences immunosuppressant trough levels significantly. We report our first clinical experience with the use of caspofungin as first-line therapy in heart and lung transplant recipients with invasive aspergillosis. Methods Caspofungin was administered at 50 to 70 mg/day in heart and lung transplant recipients with renal impairment while invasive aspergillosis was diagnosed and classified. Aspergillus serology, serologic inflammatory markers, and X-rays were taken to monitor infectious activity. Creatinine and immunosuppressant trough levels were monitored closely. Results Invasive aspergillosis was diagnosed by chest X-ray, serology, and positive sputum in 1 heart-lung, 7 heart, and 4 single-lung transplant recipients, and caspofungin was administered for a mean time of 21 ± 9 days. Basic immunosuppressants were tacrolimus in 9 patients or cyclosporine in 3. Complete remission was achieved in 10 patients (83%). Adverse effects of caspofungin were fever in 6, diarrhea in 3, and neutropenia in 1. Renal function remained stable (3.2 ± 1 mg/dl before vs 2.3 ± 0.9 mg/dl after, p = 0.07). Trough levels of all immunosuppressants did not change significantly during caspofungin treatment (10.9 ± 4.1 ng/ml before vs 9.9 ± 4.0 ng/ml after [ p = 0.31] for tacrolimus; 214 ± 98 ng/ml before vs 229 ± 88 ng/ml after [ p = 0.41] for cyclosporin A), while the administered dosage remained stable. Conclusion In heart and lung transplant recipients with invasive aspergillosis, caspofungin seemed to be an effective anti-fungal agent with a promising safety profile. Further prospective randomized trials are needed to investigate an advantageous role of caspofungin in the treatment of invasive aspergillosis.

We report on 2 children, aged 3 and 4 years, with single ventricle physiology who underwent Fontan operation in the presence of a single right lung successfully with good midterm outcome. Therefore, the absence of one lung is not a contraindication for a Fontan palliation in selected patients with optimal hemodynamics.

Left abnormal subclavian artery and right aortic arch is described as a rare cause of dyspnoea and dysphagia in paediatric patients. The optimal surgical management of such cases is not clearly established. We propose a single-stage repair by transection of the patent ductus arteriosus or ligamentum arteriosum and an additional transection of the left abnormal subclavian artery with reimplantation into the common carotid artery.

Background The aim of this study was to evaluate early and late outcomes after mechanical systemic heart valve replacement in pediatric patients. Methods Between October 1981 and December 2003, 32 children (mean age 7.2 +/- 5.4 years; 4 months - 15.9 years) underwent mechanical mitral (MVR, n = 17), aortic (AVR, n = 13) or double valve replacement (DVR, n = 2) with St. Jude Medical valves. Twenty-two patients (69 %) had undergone previous cardiac surgery. Anticoagulation self-management was used since 1995. Results The operative mortality was 3.1 %. Perioperative complications were complete heart block (n = 5), ventricular fibrillation (n = 1) and myocardial infarction (n = 1) and were exclusively related to patients with MVR. Mean calculated valve size ratio (geometric prosthesis orifice area/normal valve size area) was 1.72 (1.07 - 2.85) for AVR and 1.4 (0.88 - 3.12) for MVR. Mean follow-up was 9.1 +/- 6.6 years (range 0.4 - 23.2 years, cumulative 283 patient-years). There were two late deaths in patients with MVR. Actuarial survival after 10 years was 93.8 %. Late complications were endocarditis (n = 2), minor hemorrhagic event (n = 1), and stroke (n = 1). Anticoagulation self-management is well accepted by all patients/parents. Overall 10-year freedom from any anticoagulation-related adverse event with phenprocoumon was 89.1 % (1.2 %/patient year). Nine patients required reoperations: redo-MVR (outgrowth of prostheses (n = 3), pannus overgrowth (n = 2), closure of paravalvular leak after AVR (n = 2), partial aortic valve thrombosis (n = 1) and redo-DVR (n = 1 for endocarditis). Freedom from reoperation after 10 years was 80.9 %. Conclusions Mechanical valve prostheses are a valuable option for left-sided heart valve replacement in pediatric patients. Perioperative morbidity was exclusively related to patients with MVR. Oversizing was often possible to avoid early reoperation for outgrowth. The operative mortality and long-term morbidity are acceptable. Anticoagulation self-management is safe and well accepted.

We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only 8 3–4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials. Copyright © 2008 S. Karger AG, Basel Received: June 2, 2008 Accepted after revision: August 21, 2008 Published online: November 6, 2008 P.K. Schaefermeier Department of Cardiac Surgery, Laboratory for Tissue Engineering University Hospital of the Ludwig-Maximilians-University DE–81377 Munich (Germany) Tel. +49 89 7095 4791, Fax +49 89 7095 3465, E-Mail pschaefe@med.lmu.de © 2008 S. Karger AG, Basel 0014–312X/09/0421–0049$26.00/0 Accessible online at: www.karger.com/esr Schaefermeier /Szymanski /Weiss /Fu / Lueth /Schmitz /Meiser /Reichart /Sodian Eur Surg Res 2009;42:49–53 50 scaffolds resembling the anatomy of a native human heart valve [5] . Currently we describe a fabrication technique to generate a 3-dimensional heart valve scaffold, which was designed in the shape of the natural aortic valve, to provide temporary mechanical support for the construction of a viable and surgically feasible human heart valve. Material and Methods Prototyping Process An aortic homograft was used as a prototype to fabricate an individual heart valve scaffold with the correct anatomy of the human aortic valve. The homograft had not been accepted for heart surgery because of a positive microbiological test and was prepared for computed tomography (CT) scanning under the guideline of the laboratory for homografts at the German Heart Institute Berlin. We had previously introduced the idea of 3-dimensional reconstruction of heart valves. However, the prepared valve was scanned by CT at 2 mm slice distance and 0.1 ! 0.1 mm pixel size within all slices. The image data derived from CT were processed with our in-house software (Amira-Anaplast) which performs the image segmentation (border extraction with an appropriate density threshold). For specifying the region of valve location, the segmented images were further processed by a region-growing technique ( fig. 1 a, b). The 2-dimensional segmented images were interpolated from adjacent sections above and below to establish a visualized 3-dimensional aortic valve and root model. The 3-dimensional model was converted into a stereolithographic (STL) model and fed to the FDM 3000 stereolithography machine (Stratasys, Eden Prairie, Minn., USA) for construction of a resinic STL heart valve model. In addition, a negative cast of the ventricular side of the aortic homograft was created to construct a subsequent heart valve scaffold. Scaffold Material A polymeric material was used for the fabrication of a heart valve scaffold. Poly-4-hydroxybutyrate (P4HB; MW 700,000 by gel permeation chromatography, porosity 80%, pore size 80–240 m, thickness 300 m) is a biopolyester produced by a proprietary fermentation process (Tepha, Cambridge, Mass., USA). P4HB is a semicrystalline, thermoplastic elastomer with a melting point of approximately 60 ° C and a glass transition temperature of –51 ° C. Heart Valve Scaffold Fabrication The STL silicone model was then used to fabricate a polymeric heart valve. This consisted of 3 steps, as shown in figure 2 . Firstly, a rectangular piece of the polymer is wrapped around the negative cast of the silicone STL model (ventricular side of the STL silicone model) and trimmed off the potential sinus of Valsalva to shape a stent-like scaffold [4] . In the following step, another piece of polymer is wrapped around the stent-like polymeric scaffold and is fixed by a thermal processing technique. The upper edges of the polymer are trimmed according to the shape of the 3 leaflets, gently pressed onto the negative cast and manually molded. The third step is to use a polymer patch to form the sinus of Valsalva and the vascular wall of a valved conduit. The whole heart valve scaffold is then placed at 4–8 ° C for 24–48 h for cooling to develop the stable and exact shape of the aortic heart valve and root. Thus, in the whole process we accurately imitate the structure of the native aortic heart valve and use the thermoplastic technique to fabricate the trileaflet heart valve scaffold using a biodegradable porous polymer. Bioreactor Testing The P4HB heart valve scaffold for tissue engineering was tested in a bioreactor pulsed by a simple respirator (dual-phase control ventilator; Harvard Apparatus, Holliston, Mass., USA), with inspiration/expiration set to 30/70 and frequency to 50 strokes/ min. The testing device was completely transparent to facilitate observation of the function of the heart valve scaffold. The setup was connected to 2 sensor elements of a digital pressure monitoring device (Hellige Cardioserv, Freiburg, Germany), as described previously [5] .

Heart transplantation represents a valuable therapeutic option for patients with congenital heart disease and end-stage heart failure. We report the case of a 15-year-old patient with situs inversus and additional complex congenital malformations of the heart who underwent several previous palliative operations. Orthotopic cardiac transplantation with several technical modifications was performed successfully. At 18 months post-operatively the patient is free from rejection and doing well in New York Heart Association (NYHA) Class I status.

Purpose Currently we are exploring the impact of using rapid prototyping techniques for surgical planning and intraoperative orientation during the correction of complex congenital malformation. Description We studied a patient with a left abnormal subclavian artery and right descending aorta as a rare cause of dyspnea and dysphagia. The patient was examined by magnetic resonance imaging angiography. The image data were visualized and reconstructed. Afterward a replica of the malformation was fabricated using a rapid prototyping machine. In addition, a stereolithographic model of an intracardiac lesion (ventricular septal defect) was fabricated with data obtained from a computed tomographic scan. Evaluation Using data derived from a magnetic resonance imaging angiography or computed tomographic scan linked to proprietary software, we were able to create three-dimensional reconstructions of complex vascular pathology and intracardiac lesions. In addition, we fabricated replicas of congenital malformations using a rapid prototyping machine. The models could be sterilized and taken to the operating room for orientation during the corrective surgical procedure. Conclusions Stereolithographic replicas are helpful for choosing treatment strategies, surgical planning of corrections, and intraoperative orientation, and as demonstrations on life-like models for the patient.

Tacrolimus is a macrolide immunosuppressant frequently used after solid-organ transplantation. Moderate and severe neurologic side effects have been reported in patients receiving tacrolimus. Cerebral neurotoxicity is a rare but fatal calcineurin inhibitor-related complication, especially in kidney and liver transplant recipients. Often a reduction or a change in immunosuppressive regimen is the only means of clinical management. Herein we report a case of a 31-year-old man who developed cerebellar atrophia while under immunosuppressive therapy 9 years after heart transplantation. His neurologic constitution ameliorated after an immunosuppressant switch from tacrolimus to sirolimus.

Truncus arteriosus communis is a congenital heart malformation, which is usually repaired in the neonatal period or early infancy. Although results of repair are good, there is long-term morbidity caused by reoperations mainly owing to right ventricle to pulmonary artery conduit exchange or stenosis at the pulmonary artery bifurcation as recently reported for Contegra conduits. We present a new technique for complete autologous reconstruction of the aorta and the pulmonary bifurcation in truncus arteriosus type I and II.

Mechanical circulatory support is successfully applied to patients with low cardiac output. The MEDOS-System provides pulsatile ventricular assistance for patients of all age groups, including neonates. We report our experience with seven consecutive pediatric patients with the MEDOS-VAD. The indication was bridge to transplantation in all patients. Mean age was 7.3 +/- 6.5 years (range 0.75-16.9 years) and mean weight was 26.3 +/- 21.7 kg (range 5.9-60 kg). Perioperative survival was 100%; complications occurred in six patients (86%; two cerebral embolism/bleeding, two rethoracotomy, two exchange of pump chamber due to thrombus formation after 4 and 9 days). Mean duration of support was 20.4 +/- 10.8 days (range 6-38 days). Bilirubin decreased from 3.5 +/- 2.6 mg/d to 2.1 +/- 1.2 mg/d. Hospital mortality was three of seven patients who did not receive an organ offer in time. All patients who underwent subsequent heart transplantation (four of seven patients; 57%) were discharged from the hospital. Mechanical circulatory support with the MEDOS-System can be performed successfully in pediatric patients of any age. Secondary organ functions improve under this pulsatile circulatory assistance. Hemorrhage and thromboembolic events are the most frequent complications.

Mechanical circulatory support is successfully applied to patients with low cardiac output. The MEDOS/HIA-System provides pulsatile ventricular assistance for pediatric and adult patients. Our experience with 13 consecutive patients with the MEDOS is reported. Perioperative survival was 84.6%, complications occurred in 61% (31% thrombembolism, 23% rethoracotomy, 7% infections). Mean duration of support was 17.6 +/- 14.6 days (1-45 days). Bilirubin decreased from 3.9 +/- 2.3 to 2.7 +/- 1.6 mg/dL; creatinine from 1.6 +/- 1 to 1.4 +/- 0.8 mg/dL; lactate from 5.8 +/- 4.2 to 1.7 +/- 1.5 (P = 0.027; Wilcoxon). All patients who underwent subsequent heart transplantation (6 of 13; 46%) were discharged from hospital. For 38.5% of the patients no organ offer was received. Mechanical circulatory support with the MEDOS/HIA-System can be performed successfully for bridging to transplantation. Secondary organ functions improve under this pulsatile circulatory assistance. Hemorrhage and thromboembolic events are the most frequent complications.

Purpose The purpose of our study was to evalute the stability of an artificially seeded endothelial cell layer on porcine aortic prostheses under in vivo conditions in the arterial system. Description Ten female sheep were divided into two groups. Animals of the study group (n = 7) had dissection of their right external jugular vein for cell harvesting. Myofibroblasts and endothelial cells were labelled with PKH-26, seeded onto pretreated (10% citric acid) porcine glutaraldehyde-fixed aortic valves (Freestyle, Medtronic Inc, Duesseldorf, Germany), and the valves were implanted into the descending aorta. Controls (n = 3) received pretreated but unseeded valves. A shunt between the aortic arch and the left atrial appendage ensured systolic or diastolic leaflet motions, or both, that were documented by sonography. After 3 months the valves were explanted. Specimens for scanning electron microscopy and immunohistochemical staining were taken prior to implantation and after explantation. Evaluation A neointimal proliferation was detected in the control group. No endothelial cells were found on the leaflets and the sinuses, but erythrocytes and thrombocytes were seen entrapped within the collagen fibers. Thrombus formation was documented macroscopically and histologically on the leaflets and the sinuses. In the study group a confluent endothelial cell layer was documented on the walls and leaflets. Neither neointimal proliferation nor any clots were seen. Some cells were still labelled positively indicating their origin from the initial cell seeding. No dilatation of any prosthesis was observed, but all valves showed slight thickening of the leaflets. Conclusions The artificially seeded endothelial cell layers remained stable under in vivo conditions in the arterial system. Biocompatibility of the prostheses seemed to be improved by reduction of thrombogenicity.

The increasing numbers of patients with high risk for sternal instability and wound-healing complications after cardiac surgery requires improved concepts in bleeding control without the use of bone wax. We present an alternative technique to control bleeding from the sternal bone marrow with patches of oxidized regenerated cellulose (Nu-Knit; Ethicon, Johnson & Johnson, Somerville, NJ). Technique A 73-year-old woman with unstable angina was referred to our department for urgent surgical revascularization and mitral valve repair. In addition, the patient had insulin-dependent diabetes, chronic obstructive lung disease, and obesity (body mass index, 32.4). Median sternotomy revealed a fragile sternum and severe osteoporosis with excessive bleeding from the bone marrow. Electrocautery to the periostium was used sparingly to control bleeding, and patches of 3 9‐inch Surgicel Nu-Knit hemostat (one 6 9‐inch Surgicel Nu-Knit hemostat cut in half) were placed on each side of the sternum (Figure 1). Additionally, towels were wrapped around the absorbable hemostatic patches for their optimal fixation and for atraumatic management of the tissue before the retractor was inserted. After 2 to 3 minutes, a good hemostatic effect with the Surgicel Nu-Knit hemostat (Figure 2) was achieved. Full heparinization (active clotting time 400 seconds) was initiated for the extracorporeal circulation. Routine coronary arterial bypass grafting (3 grafts) and mitral valve repair were performed. After surgical intervention and decannulation, protamine was administered to antagonize heparin completely. The hemostatic patches were removed from the sternum, and no additional hemostatic agent was administered. Finally, the sternum was closed in a standard fashion with wires. The wound was closed in layers, with intracutaneous sutures used for skin closure. The intraoperative and postoperative course of the patient was uneventful. No enhanced bleeding, infection, or sternal wound-healing complication occurred postoperatively. To date, we have performed this hemostatic procedure in 53 patients at high risk for unstable sternum and infection. We had good or at least satisfactory intraoperative blood control in all cases. We observed no in-hospital mortality. No patient required a reoperation because of bleeding or unstable sternum. None of the patients had a deep sternal wound infection. Discussion

Background The development of hypertensive pulmonary vascular disease (HPVD) is considered a risk factor in the long-term course of patients with secundum atrial septal defects (ASD). The aim of this study was to assess the prevalence and histologic degree of HPVD and pulmonary hypertension in relation to preoperative clinical and hemodynamic data, intraoperative findings, and operative outcome in adults. Methods Lung biopsies of 75 patients, mean age 44 ± 14 years (18–71 years), with secundum ASD or sinus venosus defect including ten patients with partial anomalous pulmonary venous return were analyzed in accordance with preoperative and intraoperative findings as well as operative outcome. Lung biopsy was performed at the time of defect closure and was classified according to Heath and Edwards. Results Structural changes of the pulmonary vasculature were found in 59% of patients; grade 3 and higher changes were present in 19%. There were no statistically significant relations between histologic findings and preoperative clinical and hemodynamic data, intraoperative findings, and operative outcome. The prevalence of moderate (32–50 mm Hg) and severe (> 50 mm Hg) systolic pulmonary hypertension was 27% and 17%, respectively. Increased systolic pulmonary arterial pressure was associated with increased pulmonary vascular resistance ( p p = 0.001). Patients with a lower functional capacity had a higher prevalence of pulmonary hypertension ( p = 0.011). Conclusions The prevalence of HPVD and pulmonary hypertension in adult patients with secundum ASD or sinus venosus defect is considerable. Preoperative hemodynamic data do not predict the degree of HPVD in lung biopsy. Closure is generally advised to prevent increasing pulmonary arterial pressure and decreasing functional capacity over time.

Objective: Current prosthetic heart valves necessitate permanent anticoagulation or have limited durability and impaired hemodynamic performance compared with natural valves. We report in vivo and in vitro results with new polymeric valve prostheses that have a special design for the mitral and aortic positions. The aims are improved durability and elimination of the need for permanent anticoagulation. Methods: The mitral and aortic prostheses (Adiam Life Science, Erkelenz, Germany) are made entirely of polycarbonate urethane (PCU). The bileaflet asymmetric mitral valve mimics natural, nonaxial inflow, which creates a left ventricular vortex, saving energy for systolic ejection of blood. The trileaflet aortic prosthesis has diminished pressure loss and reduced stress and strain peaks at the commissures. The valves were subjected to long-term in vitro testing and in vivo testing in a growing calf model (20 weeks; 7 mitral and 7 aortic valves) with comparison with 2 commercial bioprostheses (7 mitral, 2 aortic). Two-dimensional echocardiography was performed after implantation and prior to sacrifice with autopsy and valve examination. Results: In vitro durability of the PCU valves was proved up to 20 years. In vivo durability and hemodynamics were superior to those of all bioprostheses. Survival of PCU valves versus bioprostheses was 7 versus 2 mitral valves and 5 versus 0 aortic valves, respectively. Two animals with PCU aortic valves died of pannus overgrowth that caused severe left ventricular outflow tract obstruction without changes in the valves. Degeneration and calcification were mild (mitral) and moderate (aortic) in PCU valves but were severe in biological valves. There was no increased thrombogenicity of the PCU valves compared with bioprostheses. Conclusion: The new flexible polymeric aortic and mitral valve prostheses were superior to current bioprostheses in animal testing.