Bernhard Schlechta

Stem cells and cardiac regeneration

Despite many advances in cardiovascular medicine, heart failure (HF) remains the leading cause of death in developed countries affecting at least 10 million people in Western Europe alone. The poor long‐term prognosis of HF patients, and immense public health implications has fuelled interest in finding new therapeutic modalities. Recent observations of the beneficial effect of stem cells on the damaged heart in animal experiments have generated tremendous excitement and stimulated clinical studies suggesting that this approach is feasible, safe, and potentially effective in humans. Cell‐based myocardial regeneration is currently explored for a wide range of cardiac disease states, including acute and chronic ischemic myocardial damage, cardiomyopathy and as biological heart pacemakers. The aim of the present manuscript is to review the work that has been done to establish the role of stem cells in cardiac repair, give an update on the clinical trials performed so far, as well as to discuss critically the controversies, challenges and future surrounding this novel therapeutic concept.

Long-term results of CMV hyperimmune globulin prophylaxis in 377 heart transplant recipients

BACKGROUND Cytomegalovirus (CMV) has emerged as the most important pathogen to affect the post-operative course after heart transplantation. We performed a retrospective analysis to evaluate the efficiency of CMV hyperimmune globulin (CMVIG) prophylaxis in preventing CMV disease in aggressively immunosuppressed patients after heart transplantation. METHODS We studied 377 heart transplant recipients who received quadruple-immunosuppressive therapy and CMVIG as sole CMV prophylaxis. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D+/R+, D+/R-, D-/R+, D-/R-) and was monitored for CMV immediate early antigen in peripheral blood cells, in urine sediments, and in throat washings; for the presence of serum CMV immunoglobulin M and CMV immunoglobulin G; and for clinical evidence of CMV-related symptoms. In addition, we compared the incidence of cardiac allograft vasculopathy and infection among the groups. RESULTS During the first 5 years after transplantation, CMV disease developed in 79 patients (20.96%). Comparison among the groups showed significantly increased risk for CMV disease in allograft recipients of organs from seropositive donors (D+, 27.31%; D-, 11.33%; p = 0.0003). We observed 6 CMV-associated deaths, all in CMV-antibody-negative recipients. Additionally CMV-positive recipients had a greater incidence of cardiac allograft vasculopathy (p = 0.048), and a greater overall infection rate (p = 0.0034). CONCLUSIONS Cytomegalovirus hyperimmune globulin administration prevents CMV disease and infection in aggressively immunosuppressed heart transplant recipients. Because fatal CMV disease in CMV-negative recipients of organs from seropositive donors could not be prevented with CMVIG alone, we recommend the additional use of prophylactic ganciclovir in this CMV-mismatched population.

Effect of obesity on outcome after cardiac transplantation

OBESITY is a well-described and significant risk factor for postoperative medical complications in surgery. High incidences of wound infection and dehiscence, thrombophlebitis, and pulmonary insufficiency have been reported. Obese surgical patients have abnormalities in cardiac, pulmonary, endocrine, and gastrointestinal function, as well as abnormalities in pharmacokinetics and pharmacodynamics. Obesity is also associated with the development of some of the most prevalent diseases of modern society: Cardiovascular as well as cerebrovascular disease, diabetes, and hypertension. More postoperative complications and the same comorbidities might also be expected in obese transplant recipients, which could lead to increased postoperative morbidity and mortality. In fact, reports on solid organ transplantation, including kidney, liver, and pancreas indicated in agreement a poorer outcome in obese organ recipients in terms of graft and patient survival. There is little information, however, on the impact of obesity on outcome after cardiac transplantation. Organ donor shortages mandate careful assessment of preoperative risk for heart transplantation to enable appropriate patient selection for this procedure. Therefore the purpose of the present study was to determine the impact of preoperative overweight and obesity as defined by body mass index (BMI 5 kg/m) on outcome after heart transplantation with regard to patient survival, surgical complications, incidence of infection, acute rejection and development of transplant coronary artery disease.

Anemia and erythropoietin levels in lung transplant recipients

An evaluation of 26 surviving outpatient lung transplant recipients at one center showed that 65% (17/26) had significant anemia (hemoglobin <11 g/L for women, <14 g/dl for men) at a median follow-up of 13.5 months after transplantation (range, 1–41 months). There were 14 men and 12 women with a mean age of 45.1 years (range, 23.1–66.7 years). Fifteen had a double allograft and 11 had a single allograft. Anemia was normochromic and normocytic/macrocytic with a tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency (transferrin saturation <20%) was found in 35% (6/17) of anemic patients, and two of them also had ferritin levels <15

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

mUg/L. In addition, vitamin B12 was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels were significantly decreased in anemic lung transplant recipients as compared with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1–41 mU/ml, vs. 53 mU/ml, 15–88 mU/ml; P<0.05). In nonanemic lung transplant recipients, erythropoietin levels were decreased too, as compared with normal controls (median, 2 mU/ml, range 1–21 mU/ml, vs. 5 mU/ml, 3–32 mil/ ml; P<0.05). Investigation of peripheral stem cells in 9 patients showed normal stimulation of erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128–1898 cells/ml) independent of erythropoietin concentrations. Analysis of putative prognostic factors, such as age, surgical procedure (double vs. single lung allograft), indication for transplantation, time after transplantation, infection status, presence of bronchiolitis obliterans, immunosuppression (

Surgical treatment of acute type a dissection: is rupture a risk factor?

pM azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial partial pressure of oxygen, did not demonstrate any difference in erythropoietin concentrations. Only the sex variable revealed a trend to higher levels in women than in men (median, 4 mU/ml, range 1–41 mU/ml, vs. 1 mU/ml, 1–16 mU/ml; P>0.05). The causes for low erythropoietin levels are not quite understood yet; however, they offer a rationale for the treatment of chronic anemia with recombinant human erythropoietin.

COMBINED HEART AND KIDNEY TRANSPLANTATION USING A SINGLE DONOR

BACKGROUND Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single centers experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

Outcome of pediatric heart transplantation: an analysis of 27 cases

BACKGROUND The purpose of this study was to evaluate the significance of aortic rupture on clinical outcome in patients after aortic repair for acute type A dissection. METHODS One hundred and twenty patients underwent aortic operations with resection of the intimal tear and open distal anastomosis. Median age was 60 years (range 16 to 87); 78 were male. Thirty-six patients had only ascending aortic replacement, 82 had hemiarch repair, and 2 had the entire arch replaced. Retrograde cerebral perfusion was utilized in 66 patients (53%). Rupture defined as free blood in the pericardial space was present in 60 patients (50%). Univariate and multivariate analyses were performed to assess the risk factors for mortality and neurologic dysfunction. RESULTS Overall hospital mortality rate was 24.2% +/- 4.0% (+/- 70% confidence level) but did not differ between patients with aortic rupture or without (p = 0.83). The incidence of permanent neurologic dysfunction was 9.4% overall, 10.5% with rupture and 8.3% without rupture (p = 0.75). Multivariate analysis revealed absence of retrograde cerebral perfusion and any postoperative complication as statistically significant indicators for in-hospital mortality (p < 0.05). Overall 1- and 5-year survival was 85.3% and 33.7%; among discharged patients, survival in the nonruptured group was 89% and 37%, versus 81% and 31% in the ruptured group (p = 0.01). CONCLUSIONS Aortic rupture at the time of surgery does not increase the risk of hospital mortality or permanent neurologic complications in patients with acute type A dissections. However, aortic rupture at the time of surgery does influence long-term survival.

Sequentielle, bilaterale. Lungentransplantation in Wien

Background. Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center’s experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. Methods. From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. Results. One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44628 months. Conclusion. HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure.

PEDIATRIC heart transplantation is now widely considered standard medical therapy for children with endstage heart disease. Transplantation has been used in the management of children with both acquired and congenital heart disease and performed successfully as early as the neonatal period. The purpose of this work is to describe the experience gained at the University of Vienna since the inception of a Pediatric Heart Transplant Program approximately 15 years ago.