Circulatory efficiency in patients with severe aortic valve stenosis before and after aortic valve replacement.

BACKGROUND: Circulatory efficiency reflects the ratio between total left ventricular work and the work required for maintaining cardiovascular circulation. The effect of severe aortic valve stenosis (AS) and aortic valve replacement (AVR) on left ventricular/circulatory mechanical power and efficiency is not yet fully understood. We aimed to quantify left ventricular (LV) efficiency in patients with severe AS before and after surgical AVR. METHODS: Circulatory efficiency was computed from cardiovascular magnetic resonance (CMR) imaging derived volumetric data, echocardiographic and clinical data in patients with severe AS (n = 41) before and 4 months after AVR and in age and sex-matched healthy subjects (n = 10). RESULTS: In patients with AS circulatory efficiency was significantly decreased compared to healthy subjects (9 ± 3% vs 12 ± 2%; p = 0.004). There were significant negative correlations between circulatory efficiency and LV myocardial mass (r = - 0.591, p < 0.001), myocardial fibrosis volume (r = - 0.427, p = 0.015), end systolic volume (r = - 0.609, p < 0.001) and NT-proBNP (r = - 0.444, p = 0.009) and significant positive correlation between circulatory efficiency and LV ejection fraction (r = 0.704, p < 0.001). After AVR, circulatory efficiency increased significantly in the total cohort (9 ± 3 vs 13 ± 5%; p < 0.001). However, in 10/41 (24%) patients, circulatory efficiency remained below 10% after AVR and, thus, did not restore to normal values. These patients also showed less reduction in myocardial fibrosis volume compared to patients with restored circulatory efficiency after AVR. CONCLUSION: In our cohort, circulatory efficiency is reduced in patients with severe AS. In 76% of cases, AVR leads to normalization of circulatory efficiency. However, in 24% of patients, circulatory efficiency remained below normal values even after successful AVR. In these patients also less regression of myocardial fibrosis volume was seen. Trial Registration clinicaltrials.gov NCT03172338, June 1, 2017, retrospectively registered.

Mechanical unloading by miniature axial flow pumps in late cardiac allograft failure due to acute rejection.

Allograft failure secondary to rejection commonly requires a multimodal treatment, ultimately including mechanical circulatory support. A few case reports have demonstrated the use of Impella-devices due to its assumed favorable safety profile in this fragile cohort. However, this treatment option does not play a role in choice of anti-rejective therapy in clinical routine up to date. We summarize our institutional experiences and literature mini-review on Impella-based treatment strategies in allograft rejection after heart transplantation. In all seven cases, three from our institution and four reported in the literature, Impella-based therapies led to hemodynamic stabilization in allograft failure secondary to rejection. Adverse events included hemolysis, non-fatal bleeding and in one patient a relevant aortic valve insufficiency occurred. All patients showed an improvement of allograft function. Two patients died in context of severe immunosuppression or late secondary organ failure. Based on the limited available data, we propose that Impella-mediated mechanical unloading represents a valuable option for hemodynamic stabilization in severe allograft failure due to rejection, enabling an initiation of causal therapy and thereby potentially representing an opportunity to prevent mortality. Furthermore, we hypothesize it might add to the traditional therapeutic approaches by facilitating recovery by decompressing the myocardium in allograft rejection.

[Ventricular long-term support with implantable continuous flow pumps: on the way to a gold standard in the therapy of terminal heart failure]. / Ventrikuläre Langzeitunterstützung mit implantierbaren kontinuierlichen Flusspumpen : Auf dem Weg zum Goldstandard in der Therapie der terminalen Herzinsuffizienz.

Mechanical circulatory support nowadays represents an important option in the treatment of patients with advanced heart insufficiency. Once developed as a bridging to heart transplantation, it is now a valuable option for permanent support in patients for whom a heart transplantation is not possible due to contraindications or a lack of available organs. Furthermore, it can be used as a bridging to myocardial recovery and explantation. The number of implantations of left ventricular assist devices (LVAD) has clearly increased in recent years and approximately one half of these implantations is already carried out in centers not specialized in transplantations. This development necessitates that every practicing physician is aware of the basic principles of mechanical circulatory support and with the possible complications. This article gives a summary of the current state of the technology and treatment of patients with long-term VADs.

Tuberculous meningitis in a lung transplanted patient.

A 57-year-old female lung transplant recipient developed tuberculosis after quadruple maintenance immunosuppression for acute cellular rejection with respiratory compromise. Deteriorating neurological status led to cerebral imaging and lumbar puncture, which showed Mycobacterium tuberculosis. Tuberculous meningitis with elevated intracranial pressure was treated for 2 weeks on a neurosurgical ward, and intensive care therapy was necessary for another 2 weeks. Complete neurological recovery was achieved after 3 months.

Adoptive T-cell therapy of a lung transplanted patient with severe CMV disease and resistance to antiviral therapy.

Infections with cytomegalovirus (CMV) can induce severe complications after transplantation, particularly in patients resistant to virostatic therapy. Adoptive transfer of CMV-specific T-cell lines has demonstrated promising results in patients after hematopoietic stem cell transplantation. However, the generation of specific T-cell lines ex vivo and their function in vivo is complicated in solid organ transplant (SOT) recipients. Here, we present the successful adoptive transfer of autologous CMV-specific T cells to a lung transplant recipient with ganciclovir-resistant CMV-pneumonia requiring mechanical ventilation. Infused T cells rapidly expanded in vivo and efficiently inhibited viral replication as confirmed by extensive longitudinal immunological monitoring. After full recovery, the patient was released from the clinic. After 4 weeks, the infection reappeared and persisted at a low level even after a second T-cell infusion. Our experimental data indicate that this could be the consequence of the late differentiated phenotype of the infused T cells and therefore their insufficient longevity in vivo. In summary, our report signifies the high therapeutic potential of adoptive immunotherapy in the treatment of SOT recipients when all other measures show no effect. Further studies have to elucidate the most potent strategies to generate antigen-specific T cells with high functional capacity and robust long-term persistence.

Renal and cardiac endothelial heterogeneity impact acute vascular rejection in pig-to-baboon xenotransplantation.

Xenograft outcomes are dictated by xenoantigen expression, for example, Gal alpha1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons postcardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants.

Troponin T levels in baboons with pig heterotopic heart transplants.

Troponin T levels have been monitored in baboons (n = 8) undergoing pig heterotopic heart transplantation, and correlated with a decrease in graft contractions and graft survival. Pig heart graft survival was from 12 to 139 days (mean 45, median 33), and graft failure was associated with predominant thrombotic microangiopathy and ischemia, with focal hemorrhage, and edema. An increase in troponin T levels 5 to 6 days before graft failure correlated closely with diminished graft contractions. An increase in troponin T was a reliable indicator that graft dysfunction was occurring.

Cellular allograft rejection affecting the donor aorta after combined heart-lung transplantation.

BACKGROUND: Infectious pseudoaneurysms of the ascending aorta are a recognized major complication after heart-lung transplantation. METHOD: This report describes an unusual and previously unreported complication, that of cellular allograft rejection, which caused a pseudoaneurysm of the donor's ascending aorta in a patient who underwent combined heart-lung transplantation. Repair was performed by primary suture after mobilization of the aortic segments. RESULT: On histological examination the resected aneurysm showed evidence of proliferative vasculitis with perivascular infiltration of the vasa vasorum by mononuclear cells. The mononuclear cells were identified as CD4+ and CD8+ by immunohistological staining. CONCLUSIONS: This report shows that cellular allograft rejection may affect the donor aorta after heart-lung transplantation and may result in pseudoaneurysm formation, even under triple-drug immunosuppression after ABO-compatible allograft transplantation.

Spleen transplantation in miniature swine: surgical technique and results in major histocompatibility complex-matched donor and recipient pairs.

BACKGROUND: Spleen transplantation (Tx) between some strains of rodents can lead to donor-specific tolerance either spontaneously or after a short course of immunosuppression. This study developed a surgical technique for spleen Tx in miniature swine to investigate its immunologic impact in a large animal model. METHODS: The preferred surgical technique of spleen Tx (n=8) involved excision of the donor spleen with its vascular pedicle to the aorta and portal vein. Carrel patches of donor aorta and portal vein were anastomosed to the abdominal aorta and inferior vena cava, respectively, of the (splenectomized) recipient. The results in four major histocompatibility complex-matched pairs that were mismatched for the porcine allelic antigen are reported. Two recipients were untreated, one received a 12-day course of cyclosporine A (CsA) alone, and one received thymic irradiation (700 cGy) and CsA. Hematopoietic cell chimerism was followed by fluorescence-activated cell sorter, and graft survival was assessed by histology. RESULTS: Spleen Tx was technically successful. In two untreated pigs, chimerism was detected in the blood (maximum 5% for 17 and 25 days) and lymph nodes (maximum 6% for 28 and 56 days), but both grafts showed histologic rejection by day 28. In two treated pigs, chimerism was present in the blood for 47 and 57 days, and rejection was prevented, with follow-up for 57 and 217 days, respectively. CONCLUSION: Spleen Tx in major histocompatibility complex-matched pairs treated with CsA+/-thymic irradiation results in prolonged chimerism and is associated with the development of in vivo unresponsiveness to the transplanted spleen.

Depletion of anti-gal antibodies in baboons by intravenous therapy with bovine serum albumin conjugated to gal oligosaccharides.

BACKGROUND: Anti-Galalpha 1-3Gal (Gal) antibodies (Ab) play a key role in the rejection of pig cells or organs transplanted into primates. A course of extracorporeal immunoadsorption (EIA) of anti-Gal Ab using an immunoaffinity column of a Gal type 6 oligosaccharide depletes Ab successfully, but Ab returns during the next few days. Although therapy with an anti-CD154 monoclonal antibody (mAb) prevents an induced Ab response to Gal or non-Gal epitopes, T cell-independent natural anti-Gal IgM and IgG return to baseline (pretransplant) levels. We have investigated the capacity of continuous i.v. infusion of bovine serum albumin conjugated to Gal type 6 oligosaccharide (BSA-Gal) to deplete or maintain depletion of circulating anti-Gal Ab. METHODS: Porcine peripheral blood mobilized progenitor cells (PBPC) obtained by leukapheresis from MHC-inbred miniature swine (n=6) were transplanted into baboons. Group 1 baboons (n=4) underwent whole body (300 cGy) and thymic (700 cGy) irradiation, T cell depletion with antithymocyte globulin, complement depletion with cobra venom factor, short courses of anti-CD154 mAb therapy (20 mg/kg i.v. on alternate days), cyclosporine (CyA) (in two baboons only), mycophenolate mofetil, and porcine hematopoietic growth factors. Anti-Gal Ab depletion by EIA was carried out before transplantation of high doses (2-4x 1010 cells/kg) of PBPC. Group 2 baboons (n=3) received the group 1 regimen (including CyA) plus a continuous i.v. infusion of BSA-Gal. To prevent sensitization to BSA, anti-CD154 mAb therapy was continued until BSA-Gal administration was discontinued. RESULTS: In group 1, Gal-reactive Ab returned to pre-PBPC transplant levels within 15-21 days, but no induced Ab to Gal or non-Gal determinants developed while anti-CD154 mAb therapy was being administered. In group 2, anti-Gal Ab was either not measurable or minimally measurable while BSA-Gal was being administered. After discontinuation of BSA-Gal, Ab did not return to pre-PBPC transplant level for more than 40-60 days, and no sensitization developed even when all therapy was discontinued. In one baboon, however, Ab to Gal type 2, but not type 6, returned during BSA-Gal therapy. CONCLUSIONS: Prevention of the induced humoral response to Gal and non-Gal epitopes by anti-CD154 mAb therapy has been reported previously by our group, but our studies are the first to demonstrate a therapy that resulted in an absence of natural anti-Gal Ab for a prolonged period. The combination of BSA-Gal and T cell costimulatory blockade may facilitate survival of pig cells and organs transplanted into primates. The return in one baboon of Ab reactive with the Gal type 2 oligosaccharide, but not type 6, indicates some polymorphism of anti-Gal Ab and suggests that, to be effective in all cases, the infusion of a combination of type 6 and type 2 BSA-Gal may be required.

Mycotic aortic aneurysms after orthotopic heart transplantation: a three-case report and review of the literature.

Mycotic aortic aneurysm is a rare yet life-threatening complication after orthotopic heart transplantation. This article reviews three cases of mycotic aortic aneurysm in heart transplant recipients developing in the first year after heart transplantation. Excision of the aneurysm and in situ reconstruction of the ascending aorta were performed with a patch of glutaraldehyde-fixed pericardium or cryopreserved aortic allograft material as a patch or conduit replacement. These cases show that early diagnosis by computed tomographic scanning, surgical treatment, high-dose parenteral antibiotics, and close follow-up are essential for successful treatment.

Plasmapheresis and cyclophosphamide in the treatment of humoral rejection after heart transplantation.

BACKGROUND: Clinical reports on humoral rejection after heart transplantation showed that these episodes were often more severe than those mediated through T lymphocytes and that the patient's prognosis was significantly worsened. METHODS: To evaluate the impact of plasmapheresis on the course of humoral rejection with hemodynamic compromise (HRHC) episodes, we retrospectively investigated the records of 1,108 heart transplant patients. All patients received triple-drug immunosuppression (cyclosporine a, azathioprine, prednisone) and cytolytic antibodies for induction. Between April 1986 and December 1990, HRHC episodes were treated with cortisone boli and cytolytic antibodies for at least 3 days (Group A). Between January 1991 and April 1999, HRHC episodes were treated with cortisone boli, cytolytic antibodies, and plasmapheresis for at least 3 days (Group B). All patients who survived their first HRHC episode received cyclophosphamide instead of azathioprine as maintenance immunosuppression. RESULTS: Altogether we observed 29 HRHC episodes. In 11 cases, no therapy could be administered or the therapy regimen did not correspond to either Protocol A or B. In the remaining 18 HRHC episodes, 7 episodes in 7 patients were treated without plasmapheresis (Group A), but only 2 patients survived, whereas in 11 HRHC episodes in 6 patients, therapy included plasmapheresis (Group B) and all patients survived (p = 0.002). Four of 6 patients who received cyclophosphamide after their first HRHC episode experienced at least 1 further HRHC episode. CONCLUSIONS: Plasmapheresis seems to improve outcomes in HRHC. However, cyclophosphamide as a maintenance immunosuppressive drug failed to prevent further humoral rejection episodes.

Electric myocardial impedance registration in humoral rejection after heart transplantation.

BACKGROUND: Because of the absent lymphocyte infiltrate, humoral-mediated rejection after heart transplantation is not diagnosed by the usual staining technique (hematoxylin-eosin method) of the endomyocardial biopsy specimen. However, humoral rejection is characterized by a distinct myocardial edema caused by capillary leakage. Because tissue edema increases the electric myocardial impedance of the corresponding tissue compartment the electric myocardial impedance method should be able to detect these episodes more reliably than biopsy. METHODS: To evaluate this hypothesis eight DLA-matched beagle dogs were subjected to heterotopic neck heart transplantation after multiple sensitization by skin grafts of the heart donor. For electric myocardial impedance registrations rectangular impulses (wide 1 msec) were applied over two intramyocardial electrodes and the impulse response was registered. Day-to-day comparisons were made and an increase of electric myocardial impedance of 10% or more was used as an indicator of rejection. To assess the influence of edema caused by electrode implantation, cortisone administration, narcosis, ischemia, or reperfusion on the electric myocardial impedance, identical electrodes were implanted in the native hearts of five additional dogs via lateral thoracotomy. These animals each received 100 mg methylprednisolone between postoperative days 20 and 22 and underwent heterotopic neck heart transplantation on postoperative day 28 without previous sensitization (protocol 2). Electric myocardial impedance electrodes were also implanted in these allografts (protocol 3). After transplantation myocardial biopsies were done every 2 days and the samples graded according to the International Society for Heart and Lung Transplantation classification in all dogs. RESULTS: Despite triple-drug immunosuppression (cyclosporine A, prednisolone, azathioprine) humoral rejection developed in all sensitized dogs as established by immunofluorescent staining of myocardial biopsy samples and functional deterioration. All episodes were diagnosed by electric myocardial impedance (sensitivity 100%), whereas only in one case the biopsy specimen was positive (International Society for Heart and Lung Transplantation grade > 1) (sensitivity 12.5%). All eight episodes could be treated successfully, that is, myocardial performance and electric myocardial impedance showed an immediate and full recovery. During the first 12 days none of the nonsensitized dogs exhibited rejection. Protocol 2 indicated that narcosis and the administration of cortisone did not per se have an influence on electric myocardial impedance and the influence of electrode implantation was negligible. Contrarily, edema caused by ischemia and reperfusion during transplantation (protocols 1 and 3) led to a significant increase in electric myocardial impedance. However, after 2 days this edema had faded away such that it no longer disturbed rejection diagnosis. CONCLUSION: We conclude that the registration of the electric myocardial impedance diagnoses humoral rejection episodes after heart transplantation not only reliably but also early, that is, before the onset of irreversible graft damage.

Xenotransplantation--how far have we come?

The immunologic barriers to xenotransplantation are summarized and approaches to overcome them briefly reviewed. Intensive investigation is being directed to the problem of acute humoral xenograft rejection, which is the major current barrier. Although the induced antibody response appears to be prevented by combination therapy with an anti-CD154 monoclonal antibody and mycophenolate mofetil, deposition of natural anti-Gal antibody on the graft endothelial cells appears to be sufficient to lead to rejection or a state of consumptive coagulopathy. Approaches towards the induction of tolerance are described. The potential microbiologic risks and physiologic incompatibilities of pig-to-human organ transplantation are also briefly discussed.

Pseudoaneurysm of the outflow graft in a patient with Novacor N100 LVAD system.

Six months after implantation of a wearable Novacor N100 left ventricular assist device, a 47-year-old patient developed a swelling that overlay the body of sternum. Computed tomographic scan of the chest revealed a pseudoaneurysm of the Novacor outflow graft. The patient was taken back to surgery and the diagnosis was confirmed at operation. Repair was performed by direct sutures via right anterolateral thoracotomy, under deep hypothermia and low flow technique. The postoperative course was uneventful.

Using aortic allograft material to treat mycotic aneurysms of the thoracic aorta.

BACKGROUND: Although mycotic aneurysms are rare in this age of antibiotics, they nevertheless represent life-threatening lesions of the aortic wall because of their high incidence of rupture and significantly high rate of recurrence. METHODS: Between March 1988 and August 1994, cryopreserved allograft material was used to treat 8 patients (mean age, 62.5 years; range, 47 to 80 years) with mycotic aneurysms of the thoracic aorta at our institution. Two patients had emergency operations; the other operations in 6 patients were elective. The aneurysms were located at the previous cannulation site of the aorta (n = 1) or at the donor/recipient aortic anastomosis (n = 1) in the patients who had heart transplantation, in the ascending aorta in 3 patients with aortic valve endocarditis, in the aortic arch in 2, and in the descending aorta in 1. The operative technique consisted of excision of the mycotic aneurysm followed by allograft patch reconstruction in 5 patients, an allograft composite graft replacement of the ascending aorta in 2 patients with endocarditis, and combined aortic allograft root replacement and allograft patch reconstruction of the ascending aorta in 1 patient. RESULTS: The underlying infections of the aorta were treated successfully in 6 patients. One heart transplant recipient had reoperation because of recurrent mycotic aneurysm after allograft patch reconstruction at the donor/recipient anastomosis. There was one early death involving a patient with Salmonella sp sepsis. CONCLUSIONS: The use of aortic allograft material for repairing mycotic aortic aneurysms is a promising and effective operative concept for managing thoracic aortic infections.

Therapeutic interventions in xenotransplantation.

Xenotransplantation, involving the transplantation of pig organs into humans, would resolve the current shortage of organs. It involves, however, a new therapeutic approach to organ transplantation. The presence of natural antibody in primates directed against Galalpha1,3Gal epitopes on pig vascular endothelium leads to early antibody-mediated rejection. An elicited antibody response against the same target epitopes as well as against nonGal antigens intensifies the immune destruction of the organ. Even the minimal deposition of antibody appears to lead to the development of a consumptive coagulopathy that can be fatal. Approaches being investigated to overcome these barriers include depletion and inhibition of natural antibody and complement, and suppression of the elicited T cell-dependent antibody and cellular responses. In addition, however, physiologic incompatibilities between human and pig, particularly those relating to coagulation, may enhance or complicate the immune process, and may require additional therapeutic measures. Current approaches aimed at achieving successful xenotransplantation also include investigation of agents that prevent potential xenozoonotic infection of the recipient. At present, therefore, the therapeutic interventions required to attempt to overcome the barriers to xenotransplantation are multiple. Work indicating progress in the breeding of pigs that do not express the critical Galalpha1,3Gal epitopes, however, is encouraging. The introduction of these pigs may greatly reduce the therapy required, and may ultimately allow the development of methods to induce tolerance to the transplanted pig organ.

Intramyocardial electrogram recordings for diagnosis and therapy monitoring of cardiac allograft rejection.

The registration of intramyocardial ECG amplitudes (IMEG) is a non-invasive diagnostic method of monitoring cardiac allograft rejection. In order to detect possible sources of error IMEG signals were recorded in heterotopic neck hearts in ten beagle dogs. Immunosuppression was based on cyclosporin A. The rejection process was followed by IMEG registrations as well as by serial myocardial biopsies. Intramyocardial electrogram recordings were made via three unipolar and three bipolar leads obtained from screw-in electrodes in both ventricles and the apex of the allograft. A 10% voltage drop was used as an indicator of rejection. In four dogs, the first rejection episode was treated with methyl-prednisolone and the therapy's success was monitored by IMEG and repeat biopsy. At autopsy the histology of each electrode circumference was correlated with the corresponding IMEG. The average sensitivity of a single lead was not acceptable (unipolar: 28%, bipolar: 47%). When the voltages of different leads were summed up the sensitivity rose to 43% (3 x unipolar), 85% (3 x bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 h. We conclude that in moderate allograft rejection (grade 2/3a ISHT classification), the rejection-related changes of intramyocardial ECG voltage amplitude (IMEG) seem to follow a "focal pattern" similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance adequate diagnostic reliability.

Intramyocardial electrogram recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.

OBJECTIVE: The purpose of this study was to prove the reliability of intramyocardial electrogram (IMEG) recordings for diagnosis and treatment monitoring of (1) cellular and (2) humoral mediated allograft rejection after heart transplantation. MATERIAL AND METHODS: Fifteen beagle dogs underwent heterotopic neck-heart transplantation. Eight of them were previously sensitized through several skin transplantations. IMEG recordings were performed daily. Donor-specific antibodies (IgG, IgM) were determinated in serum daily. Transmyocardial biopsies were performed every two days. RESULTS: In the sensitized group (group I) accelerated rejection occurred under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone on the fifth postoperative day (range: 4th-5th). All episodes were detected through IMEG diagnosis. In each case rejection could be treated successfully. In the cellular mediated group (group II), the average sensitivity for rejection diagnosis of a single lead was 24% for the unipolar and 42% for the bipolar leads. When the voltages of different leads were summed up the sensitivity rose to 36% (3 unipolar), 81% (3 bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 hours. CONCLUSION: The IMEG detects cellular and humoral mediated rejection early and with high reliability. The rejection-related changes of grade 2/3a rejection in IMEG seem to follow a Ofocal patternO similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance diagnostic reliability.

Gender-specific predictors of early mortality after coronary artery bypass graft surgery.

BACKGROUND: Female gender is a risk factor for early mortality after coronary artery bypass graft surgery (CABG). Yet, the causes for this excess mortality in women have not been fully explained. OBJECTIVES: To analyse gender differences in early mortality (30 days post surgery) after CABG and to identify variables explaining the association between female gender and excess mortality, taking into account preoperative clinical and psychosocial, surgical and postoperative risk factors. METHODS: A total of 1,559 consecutive patients admitted to the German Heart Institute Berlin (2005-2008) for CABG were included in this prospective study. A comprehensive set of prespecified preoperative, surgical and postoperative risk factors were examined for their ability to explain the gender difference in early mortality. RESULTS: Early mortality after CABG was higher in women than in men (6.9 vs. 2.4 %, HR 2.91, 95 % CI 1.70-4.96, P < 0.001). Women were older than men (+4.7 years, P < 0.001), had lower self-assessed preoperative physical functioning (-16 points on a scale from 0 to 100, P < 0.001), and had higher rates of postoperative low cardiac output syndromes (6.6 vs. 3.3 %, P = 0.01), respiratory insufficiency (9.4 vs. 5.3 %, P = 0.006) and resuscitation (5.2 vs. 1.8 %, P = 0.001). The combination of these factors explained 71 % of the gender difference in early mortality; age and physical functioning alone accounted for 61 %. Adjusting for these variables, HR for female gender was 1.36 (95 % CI 0.77-2.41, P = 0.29). CONCLUSIONS: Age, physical function and postoperative complications are key mediators of the overmortality of women after aortocoronary bypass surgery. Self-assessed physical functioning should be more seriously considered in preoperative risk assessment particularly in women.