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This report comprises the contents of the presentations and following discussions of a workshop of the German Heart Transplant Centers in Martinsried, Germany on cardiac xenotransplantation. The production and current availability of genetically modified donor pigs, preservation techniques during organ harvesting, and immunosuppressive regimens in the recipient are described. Selection criteria for suitable patients and possible solutions to the problem of overgrowth of the xenotransplant are discussed. Obviously microbiological safety for the recipient and close contacts is essential, and ethical considerations to gain public acceptance for clinical applications are addressed. The first clinical trial will be regulated and supervised by the Paul-Ehrlich-Institute as the National Competent Authority for Germany, and the German Heart Transplant Centers agreed to cooperatively select the first patients for cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of cardiovascular morbidity and mortality in premenopausal women is comparatively low, but increases sharply after menopause. The principal aim of this study was to determine whether women with ascending aortic disease (AAD) have a different reproductive history from that of an age-matched control group. Methods: In this retrospective study, women who had undergone ascending aortic aneurysm (AscAA) repair between 2000 and 2010 were asked to complete a questionnaire concerning risk factors and reproductive history. Data from 142 women with AAD were evaluated, and a subgroup (n = 64) with AscAA ‡5 cm was analyzed and compared to an age-matched random control group without known aortic diseases. Results: Almost all women were menopausal at the time of the questionnaire (98.4% vs. 90.6%, AscAA ‡5 cm subcohort vs. control, p = 0.12) and all subjects presented with a comparable age of menarche (13.7 - 2.6 years vs. 14.2 - 1.8 years, AscAA ‡5 cm subcohort vs. control, log-rank 0.04, p = 0.84). However, mean menopausal age was significantly lower in the case subcohort than in controls (48.1 - 4.8 years vs. 50.6 - 5.8 years, AscAA ‡5 cm subcohort vs. control, log-rank 8.35, p = 0.004), and reproductive life span was correspondingly shorter (34.2 - 5.2 years vs. 36.2 - 5.7 years, p = 0.04). Furthermore, hypertension was more prevalent in women with AscAA ‡5 cm compared to controls (89.1% vs. 61.9%, AscAA ‡5 cm subcohort vs. control, p < 0.001). Conclusion: Women who experience menopause at an earlier age than the regional mean could profit from screening for cardiovascular disease in general and particularly for AAD. Screening would enable early aneurysm detection and could, therefore, reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

The article presents the program and abstracts featured at the 9th Minisymposium on Xenotransplantation of the German working Group on Xenotransplantation held at Robert Kock Institute in Berlin, Germany on June 8-9, 2006. They include generation and characteristics of multi-transgenic pigs, immunologic aspects, virological aspects, islet cell and hepatocyte xenotransplantation and stem cell research.

OBJECTIVE Since 1992, homografts have been implanted in our institution. After initial sub-coronary implantation of the homograft, our preferred technique for aortic-valve replacement with homografts became root replacement, which poses a surgical challenge whenever redo procedures are necessary. The aim of the present study was to evaluate the outcome after homograft redo surgery, based on prospective data from the biggest patient cohort in Germany for this procedure. METHODS Between May 1992 and August 2009, 363 adult patients underwent aortic-valve replacement with homografts in our cardiac surgery department. Homograft replacement was indicated in 90 of these 363 patients due to degenerative or infective conditions, and these were analysed. RESULTS In these 73 male and 17 female patients (mean age at redo operation 62.0 years), homograft explantation was necessary due to infection (n = 14) or degeneration (stenosis n = 19, regurgitation > IIo n = 57). Mean time between homograft implantation and redo operation was 8.4 ± 3.6 years (range 0.0-15.5 years). Redo valve replacement through the aorta/homograft was done in 86 cases (valve into homograft wall = 80, total replacement of the homograft = 6) and trans-apical homograft replacement with an Edwards Sapien® Trans-catheter valve in four. Thirteen additional procedures were performed: bypass surgery (n = 1), mitral-valve repair (n = 6), replacement of the ascending aorta (n = 5) and tricuspid-valve repair (n = 1). Thirty-day mortality was 8.9% (n = 8, all of these patients presented with a homograft infection; five patients had a homograft reinfection). Survival rates after 1 and 5 years were 86.0% and 77.4%, respectively. CONCLUSIONS The risk for a redo procedure after aortic-valve replacement with a homograft seems to be acceptable when compared with other prostheses. Mortality was, however, elevated in patients with a homograft infection. Trans-apical procedures are safe and feasible and might be our preferred technique for the future. Valve infections still remain a contraindication for trans- apical procedures. [ABSTRACT FROM AUTHOR]

Human organ transplantation is the therapy of choice for end-stage organ failure. However, the demand for organs far exceeds the donation rate, and many patients die while waiting for a donor. Clinical xenotransplantation using discordant species, particularly pigs, offers a possible solution to this critical shortfall. Xenotransplantation can also increase the availability of cells, such as neurons, and tissues such as cornea, insulin producing pancreatic islets and heart valves. However, the immunological barriers and biochemical disparities between pigs and primates (human) lead to rejection reactions despite the use of common immunosuppressive drugs. These result in graft vessel destruction, haemorrhage, oedema, thrombus formation, and transplant loss. Our consortium is pursuing a broad range of strategies to overcome these obstacles. These include genetic modification of the donor animals to knock out genes responsible for xenoreactive surface epitopes and to express multiple xenoprotective molecules such as the human complement regulators CD46, 55, 59, thrombomodulin and others. We are using (new) drugs including complement inhibitors (e.g. to inhibit C3 binding), anti-CD20, 40, 40L, and also employing physical protection methods such as macro-encapsulation of pancreatic islets. Regarding safety, a major objective is to assure that possible infections are not transmitted to recipients. While the aims are ambitious, recent successes in preclinical studies suggest that xenotransplantation is soon to become a clinical reality.

Objective: Currently, in Middle Europe, closed and open mitral valve commissurotomy (MVC) is rarely done and has been replaced by catheter-based balloon procedures. Especially under these circumstances, data on the long-term outcomes after surgical interventions are important., Methods: From 1955 to 1989, 268 patients (75 male and 193 female patients) with mostly rheumatic or infectious mitral stenoses underwent closed (n = 151) or open (n = 117) surgical procedures. The mean age at surgery was 41.2 ± 11.1 years; 19 patients (7.1%) died within the first 30 days after surgery., Results: The 50-year follow-up was complete for 215 patients (80.2%). The survival rate at 10, 20, and 30 years after surgery was 80.2%, 58.6%, and 41.8%, respectively. The differences after closed and open MVC were nonsignificant. At the latest follow-up, 32 patients were alive and had a mean New York Heart Association functional classification of 2.7. The 10-, 20-, and 30-year freedom from reoperation rate was 93.2%, 82.9%, and 76.0% for the closed intervention group and 88.5%, 80.3%, and 78.7% for the open intervention groups. Again, the differences were nonsignificant. The main cause for reoperation was recurrent fibrosis of the mitral valve. Most patients (n = 51) received mechanical valves, 5 a bioprothesis, and 8 repeat MVC. Four patients required a third intervention., Conclusions: In Middle Europe, closed and open MVCs are now rarely performed, but the ultra-long-term results are excellent and serve as a standard for the now-established balloon valvuloplasty. MVCs remain an option for pregnant women. In third world clinical conditions, closed MVC remains a less expensive alternative., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: For short-term ventricular and pulmonary support the extracorporeal membrane oxygenation (ECMO) system using the Bio-Medicus centrifugal pump (Medtronic®, Minneapolis, MN, USA) was applied in 108 patients with cardiac low-output., Methods: From December 1996 to July 2006 the ECMO was implanted in 108 patients (73 adult, mean age: 49.3±18.0 yrs and 35 children, mean age: 1.3 ± 2.7 yrs) with mostly postcardiotomy cardiac low output. The surgical procedures included congenital heart surgery (n=35), heart transplantation (HTx) (n=21), coronary artery bypass operation (CABG) and/or valvular operation (n=33), other operations (n=6) and 13 patients with ECMO support for bridge to recovery., Results: The mean supporting time was 5.1±5.6 days. Overall, 30-day-survival was 40.2%. Best survival rates were seen after congenital heart surgery (24/35, 65.7%) and after HTx (9/21, 42.9%); the worst rates were in the group of CABG and/or valvular operations (5/33, 15.2%), only ECMO support (3/13, 23.1%) and other operations (1/6, 16.7%). Fifty-four patients died while supported by ECMO, 15 were weaned from ECMO but died in hospital, 39 patients were weaned and survived. Causes of death were multi-organ failure (40.6%), bleeding (23.2%), persistent cardiac low output (21.7%), thrombembolic events (8.7%), and graft failure (5.8%). Markers for adverse outcome were identified as older age, high body weight, increased AST/GOT levels, and lower thrombocyte count in adults; and as higher levels of serum creatinine in pediatric patients., Conclusions: ECMO support showed best results in pediatric patients after congenital heart surgery and in patients after HTx in contrast to multimorbid, older patients with often irreversible myocardial damage.

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.

Background and Purpose: Prospective randomized trials have demonstrated that early and continuous use of statins in heart transplant recipients significantly decreases cholesterol and also significantly lowers mortality and the development of transplant vasculopathy. This evaluation presents the authors' 11-year experience using simvastatin in heart transplant patients., Patients and Methods: In 1991, a prospective randomized study was initiated comparing the efficacy of simvastatin, beginning on postoperative day 4 (n = 35), with that of a dietary therapy alone (n = 37) in heart transplant patients receiving standard triple immunosuppression. After 4 years most of the patients in both groups received statins due to a significantly improved survival and a lower incidence of transplant vasculopathy., Results: After 11 years Kaplan-Meier survival rates were 77% in the simvastatin group versus 56.8% in the control group (p < 0.05). The incidence of graft coronary vasculopathy confirmed by angiography was 34.6% in the simvastatin group versus 73.9% in the control group (p < 0.01). There was no difference in organ function between the two groups., Conclusion: Statin therapy initiated in heart transplant patients early in the postoperative period plays an important role for better survival and lower incidence of transplant vasculopathy. The 11-year results of this study implicate that each heart transplant patient should receive early treatment with a statin as a matter of routine.