CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, ß=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

Proliferation signal inhibitors and post-transplant malignancies in heart transplantation: practical clinical management questions.

Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.

[Indication, management and problems of cardiac transplantation]. / Herztransplantation--Indikation, Vorgehen, Chancen und Probleme.

Cardiac transplantation (HTx) remains one of the most important options for the management of end stage heart failure which is treated with optimal medical therapy. Evolving surgical techniques (implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT)) and mechanical device-therapie (ventricular assist devices (VAD)) and medical therapies have yielded incremental improvements in outcomes. These alternatives to HTx, however, usually only postpone the occurrence of the final end stage situation. This explains why HTx remains the last option for a substantial number of especially younger severe heart failure patients with upcoming renal failure. It is very recommendable to refer such kind of patients to university-based and specialized advanced heart failure and cardiac transplant centers, in time. This allows the introduction of optimal medical therapy, the careful medical and psychological evaluation and preparation of the considered HTx, as well as the full information procedure which has to be delivered to HTx candidates. HTx candidates should be aware about outcome numbers, medication toxicities, complications of immunosuppression, as well as the ever-present threat of cardiac allograft vasculopathy, infections and neoplasias after HTx.

Effects of rapamycin on growth factor-stimulated vascular smooth muscle cell DNA synthesis. Inhibition of basic fibroblast growth factor and platelet-derived growth factor action and antagonism of rapamycin by FK506.

Rapamycin (RPM) is a potent and effective immunosuppressant which we have shown previously to inhibit intimal thickening in rat allograft and balloon-injured arteries. In this report, we have examined the effects of RPM on growth factor-induced vascular smooth muscle cell (VSMC) DNA synthesis. RPM potently inhibited platelet-derived growth factor (PDGF) (IC50 = 5 x 10(-9) M) and basic fibroblast growth factor (bFGF) (IC50 = 8 x 10(-10) M)-induced VSMC DNA synthesis. In contrast, only the highest concentrations of FK506 and CsA significantly altered PDGF- or bFGF-induced VSMC DNA synthesis. Addition of RPM (10(-9) M) at as late as 46 hr after growth factor addition still effectively suppressed bFGF- or PDGF-induced DNA synthesis by 76% and 54%, respectively. The extent of the antagonism of RPM's inhibition of bFGF-induced VSMC DNA synthesis by FK506 was inversely proportional to RPM concentration and directly proportional to FK506 concentration.

Successful management of a B-type cardiac allograft into an O-type man with 3(1/2)-year clinical follow-up.

BACKGROUND: In May 1997, a 19-year-old male patient of histo-blood group type O suffering from congenital end-stage heart failure accidentally received a cardiac allograft of type B and is still alive in fair condition. METHODS: In addition to conventional immunosuppressive therapy, plasma exchange (PEX), extracorporeal immunoabsorption (EIA), intravenous immunoglobulins (IVIG), and C1 inhibitor were used. RESULTS: Such treatment successfully reduced both IgM and IgG anti-B levels and complement hyperactivity and allowed to reach the state of accommodation without obvious signs of rejection. The patient has been surviving for 42 months; retransplantation with an O-type heart remained unnecessary. CONCLUSION: Humoral rejection has been avoided in this patient, with PEX, EIA, IVIG, and C1 inhibitor substantially contributing to this success. With future availability of such combined therapies, preferably before transplantation, vascular rejection events caused by preformed antibodies and complement (ABO mismatch or anti-HLA) could be prevented or treated.

Brief treatment with rapamycin in vivo increases responsiveness to alloantigens measured by the mixed lymphocyte response.

Rapamycin (RPM) is a macrolide fermentation product that prolongs rodent allograft survival more potently and effectively than cyclosporin A (CsA) and FK506. Experiments in vitro have shown that RPM inhibits lymphoproliferation by mechanisms of action that are different from other immunosuppressants. Much less is known, however, about the effects of RPM on immune cells in vivo compared to other immunosuppressive drugs. Others have shown that in vivo treatment with CsA suppresses the responsiveness of cells in the mixed lymphocyte response (MLR). Therefore, to investigate the effects of RPM in vivo, rats were treated with RPM and their lymphoid cells used as responder cells in the MLR. We confirmed that the proliferation of cells in the MLR was decreased after treatment with CsA in vivo. In contrast, treatment with RPM in vivo greatly increased the proliferative response to alloantigen in the MLR. These findings show that the effects of RPM and CsA on immune cells in vivo differ. Perhaps the cells proliferating in the MLR after in vivo RPM treatment play a role in the regulation of the immune system that enables this immunosuppressant to prolong allograft survival so effectively in rodents.

Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT(1) antagonists.

BACKGROUND: Erythropoietin (Epo), a growth factor produced by the kidney, is important in heart failure patients to promote oxygen delivery to tissues. Seventy-two chronic heart failure (CHF) patients at our outpatient clinic were subjected to morning serum Epo-level measurements and classified according to NYHA criteria. RESULTS: Forty-eight patients of classes III and IV had a significantly elevated serum Epo-level of 42.9+/-40.3 mIU/ml (mean+/-1 S.D.) when compared to the mean level of 24 patients of classes I and II who had a normal range mean value of 13.4+/-6.2 mIU/ml (P<0.05). Patients on angiotensin-converting enzyme (ACE) inhibitors showed a trend towards lower serum Epo-levels compared to patients treated with angiotensin-II type-1 receptor antagonists (AT(1) antagonists) (levels: 33.3+/-35.6 mIU/ml and 43.6+/-38.1 mIU/ml). This trend did not, however, reach statistical significance (P=0.36). CONCLUSION: We suggest that a desirable Epo increase in class III and IV CHF patients could be achieved by either recombinant human Epo administration or, possibly, by appropriate selection of the concomitant medical therapy. A large prospective study shall investigate the possible advantage of AT(1) antagonists over ACE-inhibitors with regard to Epo effect.

Implantable left ventricular assist systems (LVAS): recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure.

Implantable left ventricular assist systems (LVAS) consist of implantable pumps with small control consoles and power sources that can be worn externally. These systems provide far greater patient mobility and independence than external pumps with bulky control consoles. Patients with implantable LVAS can be discharged from hospital and are able to return to work and resume active sports. Most patients have received these systems as a bridge to heart transplantation. Clinical status and quality of life improve dramatically after device implantation and survival on support (60-70% after approx. 100 days of support) is acceptable compared with transplant candidates on medical therapy. Patient selection and adverse events, primarily bleeding, thromboembolism and infection, are important issues with LVAS. In the future, long-term support and bridging to myocardial recovery may become important indications for LVAS.

Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor.

BACKGROUND: Vascular smooth muscle cell hyperplasia with resulting luminal narrowing is the main histologic feature of accelerated arteriosclerosis seen after organ transplantation (transplant arteriosclerosis) and after balloon angioplasty (restenosis). It limits long-term allograft survival, as well as the success rate of angioplasty. At present, effective prophylactic and therapeutic strategies for these complications are still missing. Studies of in vivo models of accelerated arteriosclerosis induced by allogeneic or mechanical injury to the vasculature indicate that certain immunosuppressive drugs have inhibitory properties on smooth muscle cell hyperplasia. METHODS: This study summarizes the inhibitory effects of different immunosuppressive drugs in vitro on the growth factor-induced proliferation of vascular smooth muscle cells and endothelial cells isolated from human and rat thoracic aortas. RESULTS: The immunosuppressants rapamycin and mycophenolic acid were potent in inhibiting smooth muscle and endothelial cell proliferation. Cyclosporine demonstrated some inhibition of smooth muscle and endothelial cell proliferation, but the inhibitory concentration50 (IC50) values were just below toxicity levels. FK506 revealed a moderate inhibitory activity but, interestingly, only for human cells. High concentrations of leflunomide inhibited in our experiments only rat smooth muscle and endothelial cell proliferation. Methylprednisolone showed a gradual inhibition over a broad concentration interval of rat and human smooth muscle cells and of rat but not of human endothelial cells. CONCLUSIONS: These data indicate that all of the established and new immunosuppressants tested have antiproliferative properties on vascular cells. Rapamycin was by far the most potent one. Therefore immunosuppressants, especiallyrapamycin and mycophenolic acid, may be used for prevention of accelerated arteriosclerosis.

Anti-Galalpha1-3Gal IgM/IgG antibody levels in infants: do they have a clinical relevance in pediatric xenotransplantation?

BACKGROUND: Anti-Galalpha1-3Gal antibodies (anti-Gal) compose a major obstacle to xenotransplantation. As it is known, there is an immunological window during which infants are thought to have no xenoreactive antibodies. Therefore, we were interested in investigating the occurrence of these antibodies in newborns and infants up to 2 years of age. METHODS: IgM/IgG isotypes of anti-Gal from 74 serum samples of 16 mothers, with the respective cord bloods, and 42 infants of 4 age groups (Group I: day 1-6 months, II: 7-12 months, III: 13-18 months, and IV: 19-24 months) were determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA). A synthetic Galalpha1-3Gal disaccharide-polyacrylamide glycoconjugate was used for coating and monoclonal antibodies were used for the detection of heavy chain isotypes. Antibody concentrations were referred to an internal standard and expressed as arbitrary ELISA units (U). Hemagglutination titers against rabbit erythrocytes (E(R)) were determined in addition. RESULTS: Maternal serum samples showed a wide interindividual variability (IgM: 87 +/- 33 U (mean +/- SD), IgG 59 +/- 39 U) whereas in cord blood no detectable IgM was seen in presence of IgG (52 +/- 34 U). From Group I to IV there was a gradual increase of anti-Gal IgM towards an average of 70% of the adult levels whereas IgG fell to an average of approximately 20% of cord blood levels. Hemagglutination titers followed an increasing tendency with cord blood starting from 1:16 and reaching 1:256 in Group IV. CONCLUSION: The humoral immune response to the Galalpha1-3Gal epitope (alpha-Gal) in infancy follows the generally known development of specific antibodies in humans.

New concepts in organ preservation.

Organ preservation between donor and recipient is an important link in a chain that ultimately should lead to long term survival of the recipient thanks to a well-preserved, functionally intact organ. The period of organ ischaemia outside the body is subject to a number of biochemical stress factors which become known in more detail as knowledge on biochemical and immunological mechanisms improves. Efficacy of preservation fluids hence reduction of ischaemia injury may become enhanced by such additives as ion channel blockers, enzyme inhibitors, haeme oxygenase modulators, endothelin-l-inhibitors, quenchers of free radicals and anti-apoptotic agents. Many of these compounds, albeit of great theoretical interest, have not (yet?) made their way into clinical practice. This contribution is a survey of some promising agents, concentration and physicochemical interactions of which are analysed in some detail.

Perioperative risk and long-term results of heart transplantation after previous cardiac operations.

BACKGROUND: In recent years, there has been an increasing proportion of candidates for heart transplantation who have sustained one or several previous cardiac operations. This study analyzes the perioperative management and the long-term survival of patients undergoing orthotopic heart transplantation as a redo operation and compares the results with those obtained in patients undergoing transplantation as the first cardiac operation. METHODS: From October 1985 to October 1994, 204 heart transplantations were performed in 202 patients. Thirty-eight transplantations were performed in patients who had undergone prior cardiac operations because of coronary artery disease (n = 21) and valvular disease (n = 8) as well as one or several palliative or corrective procedures because of complex congenital heart disease (n = 9). These 38 patients were compared in a case-control fashion with 76 patients who underwent orthotopic cardiac transplantation as a primary cardiac procedure during the same period and using similar techniques. The majority of preoperative variables (hemodynamics, inotropic support, liver and renal function, coagulation, and priority to transplantation) were comparable in the two groups of patients. Mean age was significantly younger in the group of patients with a previous operation (42.2 +/- 9.5 versus 50.1 +/- 7.3 years; p < 0.001). RESULTS: Except the problem of more fastidious hemostasis, which is nowadays under better control since aprotinin has been routinely administered, the results show no significant difference in term of perioperative risk (hospital mortality: 5.2% in study group versus 7.8% in the control group) and long-term outcome. The 1-year survival rate was 92.7% +/- 3.6% in the study group versus 90.8% +/- 3.6% in the control group, and the 5-year survival rate was 79.4% +/- 4.5% versus 74.8% +/- 7.5%, respectively. CONCLUSIONS: These results are very acceptable and confirm the fact that carefully selected candidates for transplantation are not exposed to a particularly high perioperative risk when a prior cardiac operation has been performed. The incidences of early and late rejection episodes as well as the numbers of postoperative infections are similar in the two groups. Although multiple prior procedures do constitute significant risk factors for perioperative morbidity and mortality in isolated lung and heart-lung transplantation, this is not the case in heart transplantation.

Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to determine the risk of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses who underwent non-cardiac surgery under different regimens of perioperative anticoagulation. Data were analyzed on the basis of surgery type and underlying disease. METHODS: A series of 235 patients (mean age 63 +/- 4.5 years) with one or two mechanical heart valves underwent subsequent non-cardiac surgery comprising abdominal, vascular and thoracic, orthopedic, urologic, neurosurgery, ENT, plastic and reconstructive, and gynecologic operations. Mean interval between heart valve replacement and non-cardiac surgery was 3.9 +/- 3.3 years. Perioperative oral anticoagulation was managed by discontinuation of oral anticoagulation and intravenous heparin administration; or by discontinuation and early postoperative re-institution of oral anticoagulation without intravenous heparin; or by no withdrawal of oral anticoagulation. Patients with bioprostheses were excluded. RESULTS: Overall hospital mortality during non-cardiac surgery was 2.9%. Thromboembolic events included cerebral embolism with transient deficit (n = 3), residual defect (n = 1) and irreversible defect (n = 1), as well as peripheral embolism (n = 11). Hemorrhagic complications included wound hematoma (n = 10) and increased postoperative bleeding (n = 8) with re-exploration in five patients. Thromboembolic complications occurred most often in patients with prosthetic mitral valve and atrial fibrillation; the lowest risk was in patients with sinus rhythm after aortic valve replacement. Most complications occurred after discharge and in patients with surgery for malignancy, within 10 days of instituting oral anticoagulation, and despite a therapeutic INR value. CONCLUSIONS: Minor surgical procedures can be performed safely without discontinuing anticoagulation. When major non-cardiac surgery is planned, discontinuing oral anticoagulation and starting perioperative intravenous heparin minimizes bleeding and thromboembolic risks. Thromboembolic complications may occur within one month of surgery, despite adequate oral anticoagulation, though permanent morbidity is low.

Successful heart transplantation in a patient with Ivemark syndrome combined with situs inversus, single atrium and ventricle after total cavo-pulmonary connection.

Heart transplantation represents a valuable therapeutical option for patients with congenital heart disease and end-stage heart failure. We report the case of a young adult patient with a situs inversus and additional complex congenital malformations of the heart who underwent several prior palliative interventions, a biventricular repair being impossible. Orthotopic cardiac transplantation with several technical modifications was performed successfully at the age of 19 years.

Early and late outcome of operated and non-operated acute dissection of the descending aorta.

OBJECTIVE: At present debate continues concerning the optimal mode of treatment for type B dissections. Controversies are mainly due to discordant results regarding survival following medical or surgical treatment. We assessed early and long-term outcome of acute dissection of the descending aorta treated by emergency aortic replacement, medical treatment or delayed surgery. METHODS: Between 1980 and 1995, 225 patients were hospitalized in the medical or surgical department of our institution with the diagnosis of acute type B aortic dissection. A total of 38 patients (16.8%) underwent replacement of the descending aorta within the first week after hospital admission. Primary indications for immediate surgery were: rupturing aneurysm (n = 15), diameter of the descending aorta (n = 13), malperfusion of the thoracoabdominal aorta (n = 8) and pseudocoarctation syndrome with uncontrollable hypertension (n = 2). All other patients (n = 187) underwent primary conservative treatment on the intensive care unit, including appropriate anti-hypertensive medication. In 12 of them, surgery was denied because of age or significant concomitant diseases. RESULTS: Hospital mortality after urgent or emergency surgery was 21% (8/38 patients) for the overall time period. There has been a significant decrease in hospital mortality during the last 5 year-period (12% versus 30% between 1980 and 1994). Causes of death were: cardiac failure in 3, bleeding complications in 2, postoperative mesenteric ischemia in 2 and septicemia in one patient. From the 30 operative survivors, 9 (30%) patients required further surgery on the native aorta after a mean follow-up of 48 +/- 13 months. Hospital mortality during conservative treatment was 17.6% (33/187 patients). Main causes of death were rupture in 14, thoraco-abdominal malperfusion in 13 and cardiac failure in 3 patients, whereas in 3 patients, the cause of death could not be evaluated. In this group, 9 patients had to be shifted to early surgery during the initial hospitalization because of impending rupture (n = 4), rapidly increasing diameter (n = 2) and suspicion of intestinal ischemia (n = 3). After hospital discharge, surgery for chronic dissection was performed in 47 patients, mainly because of expanding descending aortic aneurysm. Hospital mortality was 8% (4/47 patients). Actuarial survival rates after surgery during the first admission were 85 +/- 6% at 5 years and 61 +/- 8% at 10 years, versus 76 +/- 5 and 50 +/- 7% respectively, following conservative treatment (P < 0.001). CONCLUSION: Nowadays, acute type B dissection can be treated surgically with a reasonable perioperative risk. Despite aggressive anti-hypertensive treatment, hospital mortality of primary conservative treatment is still high and a substantial percentage of patients requires surgery during initial hospitalization. Main causes of death in both groups are rupture and abdominal malperfusion: therefore, closed clinical and radiologic assessment of the whole thoraco-abdominal aorta is of utmost importance. Long-term results are satisfying; unlimited radiographic follow-up allows for detection of potential severe complications and for proper planning of elective reoperations when indicated.

Solid organ transplantation across the ABO histo-blood group barrier: a case report.

The ABO blood group system until recently constituted an insuperable barrier for solid organ transplantation, but cases of heart transplantation in infants and kidney transplantation in adults have been reported, wherein ABO-incompatible grafts have been successful. In 1990, the molecular genetic basis of three major alleles at the ABO locus was elucidated; A and B glycosyltransferases are specified by a variety of functional alleles at this locus. The antibody response to ABH antigens, namely, naturally occurring anti-A/B IgM and IgG isotype agglutinins, are controlled preoperatively by recipient conditioning using plasma exchange, immunoadsorption, and immunosuppressive regimens. We report an O-type patient who accidentally received a B-type cardiac allograft in 1997 who survived for 5 years, dying for an unrelated reason. Over a period of 45 months semiquantitatively we monitored the expression of ABO-type antigens in graft heart vessels using monoclonal antibodies on sections of formalin-fixed, paraffin-embedded biopsies. We observed a progressive change in the antigenic profile of graft endothelial cells from B- to O-type, which was first detected at 1 year posttransplant and most prominent 3 years later, the end of the observation period. No temporal relationship was observed between the transition from B to O expression, the anti-B antibody levels or the immunosuppressive regimen.

Attitudes to xenotransplantation: scientific enthusiasm, assumptions and evidence.

The use of xenografts could relieve the chronically inadequate supply of human organs for transplantation, but doubts have been expressed about the general acceptability of transplanting animal organs into human. Some researchers and clinicians have chosen to ignore negative attitudes towards clinical xenotransplantation, assuming that people will automatically embrace this new technology when it becomes available. A review of eight studies of attitudes to xenotransplantation did not reveal overwhelming support for it. Particularly negative views were expressed by acute care nurses. Primates have been the donors of choice in clinical xenotransplantation to date, but their continued use is a highly contentious option; the preferred animal donor is now clearly the pig. Animal farming for xenotransplantation is generally regarded as acceptable since animals provide food for man and are an accepted source of items for human use such as heart valves and insulin. Open debate about xenotransplantation must now take place, and present attitudes may change as a result of this. However, it remains to be seen whether xenografts will be widely accepted and used, and the extent to which the chronic shortage of organs for transplantation will thereby be alleviated.

Potential for cadaveric organ retrieval in New South Wales.

OBJECTIVES: To measure the potential for cadaver organ retrieval in New South Wales and to determine the reasons for potential donors failing to become actual donors. DESIGN: Prospective audit of all patients dying in five hospitals in New South Wales between 1 December 1989 and 30 November 1990; quality assurance of the data by independent medical specialist and if disagreement by study committee. PATIENTS: 2879 patients (100% of all deaths) yielding 364 patients with coma and 181 potential donors. OUTCOME MEASURES: Realistic medically suitable potential donor rate, missed potential donor rate, rate of potential donors with permission refused, donor rate, reasons for realistic medically suitable potential donors failing to become actual donors. RESULTS: 2879 deaths yielded 73 medically suitable potential donors, resulting in 19 actual donors, 30 missed potential donors, 19 potential donors with permission refused, and five in whom adequate resuscitation failed. The most common reason for a potential donor failing to become an actual donor was a decision by the senior medical practitioner to withdraw or not to institute ventilatory or haemodynamic support (26/73). The second major obstacle was refusal of permission by the next of kin (17/73). Assuming that the potential donor rate was that implied by the observed donor rate (13/million population/year) the projected missed potential donor rate was 9/million population/year (95% confidence interval 4 to 15) and the projected rate of potential donors with permission refused was 13/million population/year (95% confidence interval 5 to 22). Assuming that the rate of potential donors in the study hospitals was the same as in the other New South Wales hospitals, the projected donor rate for New South Wales was 18/million population/year (10 to 26); the projected missed potential donor rate was 15/million population/year (7 to 23); and the projected rate of potential donors with permission refused was 18/million population/year (10 to 27). CONCLUSIONS: The donor rate could be increased 70%-80% by overcoming the reluctance of medical practitioners to resuscitate missed potential donors and increased further by gaining permission for organ retrieval from the next of kin.

[When should the family physician contact the cardiological transplantation team?]. / Wann muss der Hausarzt mit dem kardiologischen Transplantationsteam Kontakt aufnehmen?

End stage heart failure has a poor prognosis and may be treated by cardiac transplantation, which offers these seriously sick patients a good chance of survival with an usually outstanding quality of life as compared to the preoperative state. The indication for heart transplant depends on hemodynamic and symptomatic evaluation as well as functional values. Spiro-ergometric assessment of peak oxygen consumption is used by an increasing number of cardiac transplant centres in order to achieve helpful data considering the ideal timing of transplantation. Correct assessment of the measured peak oxygen uptake is only suitable after the onset of tailored treatment of chronic heart failure; moreover, thinking about timing of heart transplantation, it is requested to be well informed on the spontaneous course of the underlying disease. Availability of appropriate organs depends on logistic factors, especially ABO blood group matching. In summary, these data may provide enough information whether and when patients should be scheduled for cardiac transplant. Ambulatory chronic heart failure clinics which are part of cardiac transplant programs are specialized institutions for the investigation of the underlying cardiac disease and for the institution of an appropriate therapy as well as for continuous observation of these patients. These chronic heart failure clinics are working very closely together with general practitioners and specialists involved in the treatment of these patients.

[Toxoplasmosis in the heart transplant patient]. / Die Toxoplasmose beim herztransplantierten Patienten.

Toxoplasmosis is a well-known problem under immunosuppressive conditions in cardiac transplant patients. In our series 12% of the patients (8 of 65) had clinical and/or serological signs of active toxoplasmosis. Due to its serious prognosis once the clinical process has started we favor a generous diagnostic interpretation of the serological results and a broad indication to drug therapy.