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Objectives: Calcineurin inhibitor-induced nephrotoxicity reduces long-term patient survival after heart transplant. Proliferation signal inhibitors, in combination with or replacing calcineurin inhibitors, may preserve or improve renal function. We evaluated the effect of calcineurin inhibitor-reduction and withdrawal in everolimus-based immunosuppression on renal function after a heart transplant., Materials and Methods: Twenty-four patients with creatinine clearance < 1 mL/s (60 mL/min) were switched from tacrolimus and mycophenolate mofetil to low-dose tacrolimus/everolimus if their heart transplant was ≤ 1 year ago (group 1, n=13) and to everolimus/mycophenolate mofetil if their heart transplant was > 1 year ago (group 2, n=11). Serum creatinine levels and calculated creatinine clearance were analyzed up to 12 months after conversion., Results: The switch in immunosuppression was associated with a significant decrease/increase of serum creatinine/creatinine clearance in both groups between baseline and month 12 (group 1, creatinine, 221.0 ± 70.7 to 159.1 ± 44.2 μmol/L (2.5 ± 0.8 to 1.8 ± 0.5 mg/dL); creatinine clearance, 0.75 ± 0.45 to 1.01 ± 0.50 mL/s (45.1 ± 26.7 to 60.5 ± 29.7 mL/min) (P < .01 each); group 2, creatinine, 247.5 ± 79.6 to 159.1 ± 44.2 μmol/L (2.8 ± 0.9 to 1.8 ± 0.5 mg/dL), creatinine clearance, 0.57 ± 0.23 to 0.93 ± 0.33 mL/s (34.1 ± 13.8 to 55.7 ± 19.6 mL/min) [P < .05 each]) with no significant group difference in the creatinine and the creatinine clearance levels after switching. No acute rejections or deaths occurred during the 12-month follow-up. Four patients (36.4%) from group 2 and 1 patient (7.7%) from group 1 discontinued everolimus because of adverse events., Conclusions: Everolimus allows calcineurin inhibitor-reduction and withdrawal after a heart transplant, resulting in improved renal function. However, adverse effects are common and lead to a high reconversion rate.

Background: Current guidelines advocate administration of inotropic agents to stabilize potential deceased heart-beating donors. A consensus on the specific agent or combination therapy is lacking. We thus initiated a retrospective analysis of patients being transplanted at our center in a matched-pair study design focusing on survival after donor pre-treatment either with norepinephrine or dopamine., Material and Methods: 936 patients (759 male; 177 female; mean age: 47.5 ± 15.4 years) were transplanted at our center between 8/1981 and 12/2010. An overall of 22 patient pairs (all male; mean age 55.4 ± 7.5 years; range 23-67 years) were matched according to our strict criteria. During follow-up (5037 ± 1791 days) 11 deaths occurred. Overall survival in both groups was not different (p=0.1438)., Results: In a sub-population analysis of all patient-pairs that completed 5-year follow-up (n=19), Kaplan-Meier analysis revealed significant superior survival of recipients that received hearts pre-treated with norepinephrine vs. dopamine pre-treatment (p=0.0368)., Conclusions: Neither norepinephrine nor dopamine pre-treatment of potential heart donors showed superior overall survival. In a sub-population of long-term survivors norepinephrine pre-treatment was associated with better survival in a rather small cohort of heart transplant recipients. These findings underscore the urgent need of further prospective multicenter randomized trials to recommend a preferable adrenergic therapy.

Background: Despite improvements in immunosuppressive therapy, the most advantageous combination for cardiac transplant recipients has not been established. This randomized controlled trial was performed to evaluate the efficacy and safety of 3 immunosuppressive protocols., Methods: Between 2003 and 2005, 78 de novo cardiac transplant recipients were randomized 2:2:1 to receive steroids and tacrolimus plus mycophenolate mofetil (TAC/MMF; n = 34), TAC and sirolimus (TAC/SRL; n = 29), or SRL and MMF (SRL/MMF) plus anti-thymocyte globulin (ATG; n = 15). Steroids were withdrawn after 6 months., Results: The 5-year survival was 85.3% for TAC/MMF, 93.1% for TAC/SRL, and 86.7% for SRL/MMF (p = 0.31 for TAC/MMF vs TAC/SIR; p = 0.47 for TAC/MMF vs SIR/MMF and p = 0.86 for TAC/SIR vs SIR/MMF). Despite the use of ATG, patients in the SRL/MMF group revealed numerically fewer freedom from acute rejection episodes: TAC/MMF, 82.4%; TAC/SRL, 85.2%; SRL/MMF, 73.3% (p = 0.33). Mean creatinine at 5 years revealed preservation of renal function in the SRL/MMF vs the TAC/MMF group (p = 0.045): TAC/MMF, 1.70±0.91 mg/dl; TAC/SRL, 1.44±0.65 mg/dl; and SRL/MMF, 1.25±0.46 mg/dl. Freedom from cardiac allograft vasculopathy was improved in the SRL/MMF group (93.3%) compared with TAC/MMF (73.5%) and TAC/SRL (80.8%) groups, reaching no statistical significance. Freedom from cytomegalovirus infection was TAC/MMF, 72.2%; TAC/SRL, 89.7%; and SRL/MMF, 86.7%. There was a trend toward improved freedom from cytomegalovirus infection with TAC/SRL vs TAC/MMF (p = 0.076). More frequent discontinuations of study medication occurred in SRL-based immunosuppression protocols (TAC/SRL vs TAC/MMF, p = 0.034; SRL/MMF vs TAC/MMF, p = 0.003)., Conclusions: The 3 strategies yield no survival advantage at 5 years, with higher numeric rates of rejection and adverse effects in the calcineurin inhibitor-free arm. A trend was observed in favor of freedom from cardiac allograft vasculopathy and preservation of renal function in the calcineurin inhibitor-free arm. However, the clinical relevance on outcomes is unclear because only few patients were receiving the assigned treatment protocols., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely published. Therefore, we collected long-term follow-up data of an intervention cohort 10 years after randomization., Methods: Ten-year follow-up data of 60 patients included in a prospective, randomized trial between 1998 and 2000 were analyzed as intention-to-treat (TAC-MMF n=30; CsA-MMF n=30). Baseline characteristics were well balanced. Cardiac allograft vasculopathy (CAV) was graduated in accordance with the new ISHLT classification., Results: Survival at 1, 5, and 10 years was 96.7%, 80.0%, and 66.7% for TAC-MMF and 90.0%, 83.3%, and 80.0% for CsA-MMF (P=ns). Freedom from acute rejection (AR) was significantly higher in TAC-MMF versus CsA-MMF (65.5% vs. 21.7%, log-rank 8.3, P=0.004). Freedom from ISHLT≥CAV1 after 5 and 10 years was in TAC-MMF 64.0% and 45.8%, and in CsA-MMF 36.0% (log-rank 3.0, P=0.085) and 8.0% (log-rank 9.0, P=0.003). No difference in long-term results for freedom from coronary angioplasty or stenting, renal dysfunction, diabetes mellitus, CMV infection, or malignancy was detected., Conclusion: Cross-over effects because of treatment switch may result in impairment of significance between the groups. The long-term analysis resulted in a significant difference in manifestation of CAV between the groups after 10 years. Less rejection in the TAC-group might have contributed to the lower incidence of CAV. Superior freedom from AR and CAV in the TAC-MMF group did not result in better long-term survival.

This paper presents a rare case of facial soft tissue infection caused by the bacterial strain of Rothia mucilaginosa. Odontogenic background of infection and initial clinical presentation suggested the presence of typical bacterial flora and uncomplicated course of treatment. However, despite surgical intervention and broad-spectrum antibiotic therapy, the expected improvement of a clinical status was not achieved. Only detailed bacteriological examination allowed to establish a bacterial pathogen and start a targeted antibiotic therapy. The unusual clinical course was monitored by imaging CT examination and further surgical interventions. A significant improvement was obtained in the third week of hospitalization and further antibiotic therapy was continued by means of outpatient treatment. Rothia mucilaginosa infection together with dental intervention is a rare case, since most of the reports in the literature concern the patients with decreased immunity. In such patients, the most common areas of infection were: the peritoneum, lung tissue and meningeal spaces of the brain and the presence of a foreign body.

Background: Gender differences between donor and recipient might have an impact on the outcome after heart transplantation (HT). Data of more than 67,000 patients registered at the International Society of Heart Lung Transplantation (ISHLT) were reviewed focusing on the influence of gender differences on short- and long-term outcome after HT., Methods: We performed a retrospective analysis of 67,855 cardiac allograft recipients. They received orthotopic HT between January 1, 1980 and June 30, 2009. In contrast to other studies the data for gender differences (donor gender and recipient gender) were calculated with respect to actuarial and conditional survival (without 30-day mortality)., Results: One-year survival was highest in male recipients of male donor hearts (mR/mD: 83.74%). The lowest 1-year outcome showed male recipients of female donor organs (mR/fD: 78.95%). Best 5-year survival rates were shown by male recipients with male donor organs (70.75%, p < 0.0001). These differences disappeared in survival conditional to 1 year, indicating that gender predominantly influences short-term outcome., Conclusions: The combination male recipient/female donor carries a higher risk for early mortality, whereas female recipients/male donor reveals favorable short-term results. Gender-matched HT would be ideal, but not suitable in practice because of the shortage of organs., (Georg Thieme Verlag KG Stuttgart · New York.)

Dentigerous cysts are characterized by slow and non-symptomatic growth. Usually they are recognized accidentally during the radiological examination of patients with an occlusion defect or dental age different than growing age. In the case described, the patient presented for dental treatment with the complaint of an occlusion defect and the appearance of a right deciduous maxillary lateral incisor (52). Radiological examination showed the presence of a horizontally positioned maxilla right lateral incisor (12) and dentigerous cyst of tooth 13 (right canine) in the maxilla sinus. After surgical consultation the cyst enucleation and extraction of the unerupted maxillary right canine were performed. Four months later the orthodontic treatment began.

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

Background: Lung transplantation for end-stage pulmonary disease is an established procedure and the number of transplantations is increasing worldwide even in developing countries. Usually donor lungs are transported in an inflated state and the bronchi are closed with a stapler device., Case Report: We present a technique that avoids costly stapler devices and is even less time consuming than reloading the staplers. After both lungs are inflated the separation of the two main bronchi is facilitated by using sterile umbilical cord clamps for the bronchus closure. We did not experience any air leaks and since the bronchi are resected prior to implantation there is always enough space to place the clamps., Conclusions: The umbilical cord clamp technique reduces the explantation costs for lung retrievals significantly. The technique is less time consuming and offers equal safety compared to stapler devices.

Present study evaluates clinical feasibility of cardiac dual-source computed tomography angiography (DSCTA) to detect significant coronary stenosis because of chronic allograft vasculopathy (CAV) after heart transplantation (HTX). An overall of 51 consecutive heart transplant recipients (43 men, 8 women, mean age: 52.3 ± 13.6 years) underwent DSCTA 1 ± 2 days before annual routine invasive coronary angiography (ICA). Three patients were excluded from further analysis. Total 714/717 (99.6%) segments in remaining 48 patients were depicted in diagnostic image quality by DSCTA with three vessel segments in two patients being additionally excluded because of motion artefacts. On a segment-based analysis, sensitivity, specificity, and diagnostic accuracy (DA) for detection of significant stenosis were calculated as 100%, 98.9% and 98.9% respectively. On a patient-based evaluation, sensitivity, specificity and DA were 100%, 86.0% and 93.0% respectively for remaining 46 patients. Negative predictive value (NPV) was 100%. DSCTA enables diagnosis and especially the exclusion of significant coronary artery stenosis in patients after HTX with a high NPV. The low rate of excluded vessel segments compared with former studies indicates improvement in image acquisition and robustness of latest scanner technology and thus may make subsequent annual invasive coronary angiography unnecessary., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

An interventional lung assist membrane ventilator (iLA) for arteriovenous extracorporeal CO2 removal was connected to a small-diameter femoral artery by use of a chimney graft in an underweight patient with acute respiratory failure and a previous history of heart-lung transplantation. This concept offers additional therapeutic options in underweight patients requiring extracorporeal CO2 removal with arterial vessels that are too small for percutaneous arterial cannulation with standard-sized percutaneous insertable iLA cannulae., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Gender differences between donors and recipients might have an effect on outcome after heart transplantation. Literature and registries reveal controversial results. We reviewed 1000 heart transplantations at our center focusing on the influence of gender differences on short- and long-term outcome after heart transplantation., Materials and Methods: We performed a retrospective analysis of 1000 (960 primary and 40 redo-heart transplantations) between August 1981 and July 2008. In contrast to other studies, the data for gender differences (donor gender and recipient gender) were evaluated for recipient survival and survival conditional to early mortality., Results: Female donors are significantly older than male donors (females, 36.5 ± 14.5 years; males, 31.2 ± 13.8 years). One-year survival was significantly inferior in male recipients receiving female donor hearts (mR/fD: 73.7%) compared to females receiving male donor organs (fR/mD: 90.9%) (P = .045). Univariate analysis revealed that, for recipients who survived > 1 year, survival at 10 years was significantly greater for female donors and female recipients (90%) than it was for male donors and male recipients (72%; P = .034). Multivariate analysis showed that the gender combination with female donors and female recipients was an independent indicator for greater long-term survival (P = .04)., Conclusions: The gender combination of female donors and male recipients had a greater risk for early mortality after heart transplantation, and the combination of male donors and female recipients resulted in favorable short-term outcomes. In long-term follow-up, recipients of hearts from female donors had better survival, especially female recipients.

Heart failure, life-threatening arrhythmias, and sudden cardiac death are common complications in patients with advanced chronic cardiac allograft rejection--the major limiting factor of long-term survival after heart transplant. In patients with sustained cardiorespiratory arrest refractory to cardiopulmonary resuscitation extracorporeal membrane oxygenation therapy is a therapeutic option. We report the case of a 6-year-old girl with severe chronic allograft vasculopathy who was successfully bridged to cardiac retransplant through extracorporeal membrane oxygenation therapy after prolonged cardiopulmonary resuscitation. Our case demonstrates extracorporeal membrane oxygenation as a rescuing therapeutic option in high-risk, bridge-to-transplant patients, with cardiac arrest. Even after prolonged cardiopulmonary resuscitation, there were no neurologic events, and our patient recovered without any neurologic damage.

The Berlin Heart EXCOR ventricular assist device provides pulsatile ventricular assistance. It can be used for univentricular or biventricular support. However, pre-, intra-, and postoperative complications (e.g., bleeding, anastomotic insufficiency) are frequent. We present herein a detailed description of our modified implantation technique in order to facilitate further clinical use of the system., (© 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Medical and psychosocial factors are related to 1-year outcomes in the Waiting for a New Heart Study. With increased use of mechanical circulatory support devices (MCSD) over the course of the study, we can now evaluate these variables as predictors of MCSD in an extended follow-up., Methods: Analyses focused on 313 MCSD-free patients (82% men; aged 53 ± 11 years) newly listed for heart transplantation (HTx). Variables assessed at time of listing included psychosocial risk (depression, social isolation), quality of life, waiting list stress, and medical risk (Heart Failure Survival Score, pulmonary capillary wedge pressure). Cumulative incidence functions and cause-specific Cox models examined the association of medical and psychosocial risk (low: non-depressed and socially integrated; medium: depressed or socially isolated; high: depressed and socially isolated) with time until MCSD, considering covariates and competing outcomes (death, high-urgency transplantation [HU-HTx], elective HTx, and delisting due to clinical improvement or deterioration)., Results: Psychosocial risk groups were comparable regarding demographics, medical parameters, and quality of life, but differed in waiting list-related stressors. During follow-up (median, 326; range, 5-1,849 days), 26 patients received MCSD, 53 died, 144 underwent HTx (103 in HU status), and 53 were delisted (15 deteriorated, 31 improved). Non-depressed and socially integrated patients did not require MCSD. Controlling for medical risk, psychosocial risk significantly contributed to MCSD, HU-HTx, and improvement; medical risk and female gender predicted death (p < 0.05)., Conclusions: Psychosocial risk at time of listing affects the prognosis of HTx candidates beyond medical risk. Psychosocial interventions may help to stabilize patients' health., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21., Methods and Results: The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (P < 0.01)]. In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (P < 0.05) and protein expression by 24% in HMECs by oxLDL (P < 0.05)., Conclusions: The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques.

Background: Left atrial cardiac myxomas are among the most common cardiac masses. However, occurrence of left atrial myxomas in post-transplant patients is very rare and often misdiagnosed as left atrial thrombus formation., Case Report: We report the case of a 67-year old female, who was referred due to suspected left atrial thrombus but was found to have a pediculated mass at the suture line of the left atrium on cardiac MRI. After resection, the diagnosis myxoma was confirmed histologically and the donor origin of the myxoma was proven by tissue typing., Conclusions: Despite a rare entity, atrial myxomas may occur in post cardiac transplant patients and may therefore support the role of advanced imaging techniques in patients with suspected left atrial masses.

Purpose of Review: The impact of donor and recipient sex on outcome after heart transplantation (HTx) is discussed controversially. Therefore, the recent findings in this field were reviewed., Recent Findings: The combination male recipient/female donor increases the risk for early mortality, whereas other sex constellations yield similar outcomes after HTx. In the long-term follow-up, survival of female recipients is superior, especially in the combination female recipient/female donor. Female recipients of male donor hearts are more susceptible to cellular rejection episodes. Their superior long-term outcome, however, is not affected by that., Summary: Sex matching in HTx, although desirable, is not always possible without prolonging waiting times for the desired donor heart. The combination female donor-male recipient should be evaluated with caution.

Purpose: Despite improvements in immunosuppressive therapy, chronic rejection, renal toxicity and malignancy are the major obstacles for long-term success after heart transplantation. We performed the worldwide first pilot-trial to evaluate the efficacy and safety of a de-novo calcineurin-inhibitor (CNI)-free immunosuppressive protocol. Between May 2003 and April 2005, 15 de-novo cardiac transplant recipients were assigned to receive sirolimus, mycophenolate mofetil and steroids. Antilymphocyte induction was given for 5 days; steroids were withdrawn after 6 months. A total of six of 15 patients received cytomegalovirus (CMV)-prophylaxis for high-risk CMV constellation (R-/D+)., Results: Survival at 1 and 5 years was 87.5%. Freedom from biopsy-proven rejection was 71.3% at 1 year and 59.4% at 5 years. Freedom from angiographically detectable vasculopathy was 100% after 5 years and only one CMV infection occurred. Mean serum creatinine was 1.43 ± 0.31 mg/dl prior to heart transplantation (HTx), 1.29 ± 0.56 mg/dl at 1 year and 1.23 ± 0.53 mg/dl at 5 years. Cholesterol was 203 ± 32 mg/dl at 1 year and 199 ± 40 mg/dl at 5 years despite statins, and hypertriglyceridaemia (223 ± 97 mg/dl) persisted after 5 years. No new-onset diabetes occurred. Surgical interventions for pericardial effusions were necessary in five patients. Nine patients discontinued sirolimus treatment temporarily because of side-effects (four acute rejections, three delayed wound healing and two gastrointestinal toxicity), all nine patients were reintroduced to sirolimus after the side-effects resolved., Summary: CNI-free immunosuppression is possible and long-term results are favourable for survival, malignancy, renal function, CMV infections and vasculopathy. On the other hand, de-novo CNI-free immunosuppression after HTx is less efficacious in preventing acute rejection and has an inferior side-effect profile.

Background: The angiographic incidence of coronary dilatation (CD) in the nontransplant population is approximately 0.2% to 5%. The endothelial-dependent and -independent causes for CD are postulated. So far, the incidence and prognosis of CD after heart transplantation is unknown., Methods: We retrospectively analyzed the annual coronary angiographies of 688 heart transplant recipients regarding the incidence of CD (defined as ≥1.5-fold localized increased vessel diameter or diffuse dilatation involving more than 50% of the coronary artery). A subgroup analysis of coronary epicardial (quantitative angiography) and microvascular (doppler flow measurement) vasomotor function in response to acetylcholine (endothelial dependent) and adenosine (endothelial independent) as well as intravascular ultrasound was performed in 177 patients., Results: CD was detectable in 26 patients (3.8%) and was associated with stenosing coronary artery disease in 27% of the patients. Segments with CD tended to have less intimal hyperplasia compared with nondilated segments. A diffuse dilatation (type I-II) was present in 63% of the recipients. The right coronary artery was always involved. The patients with CD (5 of 177) showed a 31% reduced flow velocity in the dilated coronaries compared with the nondilated coronary arteries (P=0.03). Microvascular endothelial-independent function was impaired in CD by -29% (coronary flow reserve mean 1.9 vs. 2.7; P=0.04), whereas endothelial-dependent response was unchanged. Epicardial endothelial-dependent and -independent responses were not different between the groups. Incidence of CD was not associated with limited survival., Conclusion: The incidence of CD in the nontransplant population is similar to that in the transplanted population. However, the latter shows a more diffuse extent. Heart transplantation patients with CD had microvascular endothelial-independent functional limitations and flow deceleration, whereas survival was not affected.

Background: Cardiac allograft vasculopathy (CAV) still limits survival after heart transplantation. Currently available noninvasive tests are of inferior value to detect CAV, and thus invasive coronary angiography (ICA) is frequently performed. Cardiac dual-source computed tomography calcium scoring (DSCTCS) offers the possibility to detect coronary calcifications, which might serve as a noninvasive marker of CAV. This study sought to evaluate its clinical feasibility., Methods: One hundred sixty-one patients (130 men; 31 women; mean age: 50.5±12.1 years) underwent DSCTCS 1±2 days before annual routine ICA. Mean posttransplant time was 73.7±49.6 months. The results of DSCTCS were compared with ICA., Results: In 100 patients (85 men; 15 women; mean age: 51.5±12.3 years), coronary calcifications were detected, and in 61 patients (45 men; 16 women; mean age: 49.0±11.7 years), coronary calcifications were excluded. ICA excluded CAV in 82 patients (63 men; 19 women; mean age: 48.6±11.9 years). In 79 patients (67 men; 12 women; mean age: 52.5±12.2 years), CAV was detected of whom 11 patients needed stent implantation. No statistically significant difference of DSCTCS in patients without (17.2±29.5; range: 0-190) and with CAV (33.4±66.8; range: 0-385) was observed (P=0.133). Moreover, 4 of 11 (36.4%) severely diseased patients had a calcium score of zero. Sensitivity, specificity, negative predictive value, and positive predictive value for CAV detection (calcium score threshold >0) was calculated as 72.2%, 47.6%, 47.7%, and 57.0%, respectively. Diagnostic accuracy was 59.6%., Conclusion: DSCTCS is not a valuable noninvasive modality for CAV detection and thus not recommended in clinical practice. Moreover, we hypothesize that it represents preexisting or de novo traditional coronary atherosclerosis than CAV.

Objectives: Studies carried out to date suggest that the interrupted suture technique using U-Clips for anastomoses in coronary surgery may be superior to the standard running polypropylene suture. The purpose of this study was to compare safety and effectiveness of a central T-graft anastomosis constructed with the left internal thoracic artery (LITA) in situ (to the left anterior descending (LAD)) in which the free right internal thoracic artery (to the circumflex branch of the right coronary artery (RCX)) was implanted (RITA-to-LITA) using either self-closing nitinol U-Clips or simple continuous suture. We hypothesized that internal thoracic arteries could adapt their diameter to the blood flow., Methods: Thirty patients underwent total arterial revascularization using a T-graft constructed with free LITA in situ to LAD in which the free RITA to the circumflex artery was implanted (central T-graft anastomosis). In all cases, free RITA was used as a sequential graft with two peripheral anastomoses. Patients were randomly assigned to two groups: in group A (n=15), central T-graft anastomosis was performed using a standard 8/0 polypropylene running suture. In group B (n=15), central T-graft anastomosis was performed using U-Clips. Intra-operative transit time flow measurements were recorded. Patency control was performed in 30 patients 2 weeks and 6 months postoperatively, using 64-slice computed tomography (CT) angiography. The diameter of the LITA was measured proximal and distal and the diameter of the RITA distal to the central T-graft anastomosis., Results: Perioperative results were similar in the two groups (P=ns). Intra-operative transit time flow measurement showed patent grafts in all patients. There were no hospital deaths. Two weeks postoperatively, all grafts were patent. At 6-month follow-up, one RITA and one LITA (both in group B) were closed distal to the central T-graft anastomosis. There was no death and no re-intervention during follow-up. Statistical analysis showed no significant changes in graft diameters after 2 weeks and 6 months in both groups., Conclusions: The U-Clip anastomosis technique is in our experience safe but not superior to the standard running suture using polypropylene material. Remodeling of the ITA grafts close to the central T-graft anastomosis was neither observed for the standard running suture nor for the U-Clip anastomoses., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Invasive pulmonary aspergillosis is a severe complication after solid organ transplant, with a high mortality rate. We present a 45-year-old male heart transplant recipient who developed fever, progressive worsening of dyspnea, and productive cough without response to antibiotics. Diagnosis of invasive pulmonary aspergillosis was made based on clinical, laboratory, and radiographic findings. The patient was treated successfully with combined antifungal therapy (voriconazole and micafungin). This case report highlights the importance of a high degree of clinical suspicion to allow curative treatment of invasive aspergillosis and the efficiency of new antifungal drugs.

Objective: The use of homografts for aortic valve replacement (AVR) is an alternative to mechanical or biological valve prostheses, especially in younger patients. This retrospective comparative study evaluated our single-center long-term results, with a focus on the different origins of the homografts., Methods: Since 1992, 366 adult patients have undergone AVR with homografts at our center. We compared 320 homografts of aortic origin and 46 homografts of pulmonary origin. The grafts were implanted via either a subcoronary technique or the root replacement technique. We performed a multivariate analysis to identify independent factors that influence survival. Freedom from reintervention and survival rates were calculated as cumulative events according to the Kaplan-Meier method, and differences were tested with the log-rank test., Results: Overall mortality within 1 year was 6.5% (21/320) in the aortic graft group and 17.4% (8/46) in the pulmonary graft group. In the pulmonary graft group, 4 patients died from valve-related complications, 1 patient died after additional heterotopic heart transplantation, and 1 patient who entered with a primary higher risk died from a prosthesis infection. Two patients died from non-valve-related causes. During the long-term follow-up, the 15-year survival rate was 79.9% for patients in the aortic graft group and 68.7% for patients in the pulmonary graft group (P = .049). The rate of freedom from reoperation was 77.7% in the aortic graft group and 57.4% in the pulmonary graft group (P < .001). The reasons for homograft explantation were graft infections (aortic graft group, 5.0%; pulmonary graft group, 6.5%) and degeneration (aortic graft group, 7.5%; pulmonary graft group, 32.6%)., Conclusion: Our study demonstrated superior rates of survival and freedom from reintervention after AVR with aortic homografts. Implantation with a pulmonary graft was associated with a higher risk of redo surgery, owing to earlier degenerative alterations.

Background: In this prospective study we investigated the impact of the proton pump inhibitor (PPI) pantoprazole on the bioavailability of mycophenolic acid (MPA) after oral administration of enteric-coated mycophenolate sodium (EC-MPS; Myfortic) in heart or lung transplant recipients. Previously we demonstrated that pantoprazole reduces the MPA exposure of mycophenolate mofetil (MMF; CellCept) by 34% in area under the concentration-time curve (AUC). Because gastrointestinal side-effects are common after organ transplantation, we investigated the effect of PPI on MPA levels in patients receiving EC-MPS., Methods: MPA plasma concentrations and inosine monophosphate dehydrogenase (IMPDH) activity at baseline, 30 minutes and 1, 2, 3 and 4 hours were obtained from 21 patients. These patients were treated with pantoprazole 40 mg once daily and EC-MPS twice daily at a mean dose of 960 mg. Measurements were repeated after pantoprazole withdrawal., Results: MPA concentrations and IMPDH activities did not reveal any significant difference during PPI treatment and after withdrawal. MPA AUC, MPA C(max) (maximal MPA concentration), the time until C(max) was reached (T(max)) and IMPDH activity AUC all showed no significant difference., Conclusion: We did not find an influence of pantoprazole on EC-MPS pharmacokinetics such as we did for MMF in our previous investigation. A further prospective, large, cross-over study is planned to support these preliminary results. Given that MPA exposure by AUC correlates with the incidence of acute rejection episodes and transplant vasculopathy, the present findings may have clinical implications., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Aims: We sought to determine whether circulating vascular progenitor cells, such as endothelial progenitor cells (EPCs) or smooth muscle progenitor cells (SPCs), were associated with the severity of cardiac allograft vasculopathy (CAV)., Methods and Results: CD34(+)CD140b(+) SPCs and CD34(+)KDR(+) EPCs were measured in the peripheral circulation of 187 adult heart transplant recipients by flow cytometry. Cardiac allograft vasculopathy was quantified by angiography using a CAV-specific scoring system. Cardiac allograft vasculopathy was present in 84 patients (44.7%) and was classified as mild in 59 and severe in 25 cases. Circulating SPCs were more frequently detectable in CAV patients than in patients without CAV. The number of CD34(+)CD140b(+) cells showed a stepwise increase in patients with moderate and severe CAV. Smooth muscle progenitor cell counts were higher in patients with coronary stent implant compared with unstented patients with CAV. In contrast, peripheral CD34(+)KDR(+) EPC counts were not changed in CAV patients. Plasma CXCL12 levels correlated with the degree of CAV and SPC counts. None of the different immunosuppressive drug regimes was related to the SPC count or the CXCL12 levels. A multivariate regression analysis revealed that the SPC count was independently associated with the presence of CAV., Conclusion: Circulating SPCs, but not EPCs, and plasma CXCL12 concentrations are elevated in CAV patients, indicating that they play prominent roles in transplant arteriosclerosis.

Background: Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate. However, heart tissue contains high concentrations of tissue factor, presumably enabling bleeding to be stopped immediately in this vital organ. The distribution of pro- and anti-coagulatively active factors in human heart tissue has now been determined in relation to the types of microvessels., Methods and Results: Samples of healthy explanted hearts and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin was found throughout the interstitial space. Tissue factor was packed tightly around arterioles and capillaries, whereas the tissue surrounding venules and small veins was practically free of this starter of coagulation. Thrombomodulin was present at the luminal surface of all vessel segments and especially at venular endothelial cell junctions. Its product, the anticoagulant protein C, appeared only at discrete extravascular sites, mainly next to capillaries. These distribution patterns were basically identical in the healthy and diseased hearts, suggesting a general principle., Conclusions: Venular extravasation of plasma proteins probably would not bring prothrombin into intimate contact with tissue factor, avoiding interstitial coagulation in the absence of injury. Generation of activated protein C via thrombomodulin is favored in the vicinity of venular gaps, should thrombin occur inside coronary vessels. This regionalization of distribution supports the proposed physiological heterogeneity of the vascular barrier and complies with the passage of plasma proteins into the lymphatic system of the heart., (Copyright © 2010 S. Karger AG, Basel.)

We evaluated two composite risk scores, (Heart Failure Survival Score, HFSS; German Transplant Society Score, GTSS), and depression as predictors of mortality and competing waiting-list outcomes [high-urgency transplantation (HU-HTx), elective transplantation, delisting because of clinical improvement] in 318 heart transplant (HTx) candidates (18% women; aged 53 ± 11 years) from 17 hospitals and newly registered with Eurotransplant. Demographic variables and depression (Hospital Anxiety and Depression Scale, HADS) were assessed using questionnaires. Variables to compute HFSS and GTSS, age, medications, and outcomes were provided by Eurotransplant. At 12 months, 33 patients died, 83 received urgent HTx, 30 elective HTx, and 17 were delisted because of improvement. Applying cause-specific Cox regressions, only the HFSS was significantly associated with 1-year mortality [HR = 0.64 (95% CI = 0.43-0.95), P = 0.029]. The GTSS was the strongest predictor of HU-HTx [HR= 1.02 (95% CI = 1.01-1.02), P < 0.001]. Low depression scores contributed significantly to clinical improvement, even after adjusting for age and risk scores [HADS: HR = 0.12 (95% CI = 0.02-0.89), P = 0.039]. These findings confirm the usefulness of composite risk scores for the prediction of mortality and HU-HTx, validating both scores for their intended use. The finding that depression was an independent predictor of the waiting-list outcome clinical improvement suggests that considering patients' psychological attributes in addition to their medical characteristics is advisable., (© 2010 The Authors. Journal compilation © 2010 European Society for Organ Transplantation.)

Allosensitization represents a major obstacle to successful re-transplantation since circulating antibodies can elicit antibody-mediated rejection episodes with subsequent graft failure. Since sensitization is primarily considered a contraindication to transplantation the duration for patients waiting for a suitable donor organ to become available is considerably prolonged. Herein, we report on the successful application of a Luminex-based virtual crossmatch approach to facilitate combined third-time cardiac and de novo renal transplantation in a sensitized patient with sustained antibody-mediated cardiac allograft rejection., (© 2009 John Wiley & Sons A/S.)

Animal studies suggest that the endocannabinoid system (ECS) plays a role in the regulation of myocardial contractility and in the pathogenesis of heart failure. The current study aimed to proof the existence of endocannabinoid receptors on human ventricular myocardium and to determine whether human chronic heart failure (CHF) is associated with changes in endocannabinoid receptor expression and distribution. Expression of cannabinoid receptor 1 (CB1) and cannabinoid receptor (CB2) on human heart was assessed by means of real-time PCR and immunohistochemistry. On healthy human left ventricular myocardium, mRNA transcripts of CB1 and CB2 receptors were expressed in an almost equal proportion. In patients with CHF, mRNA expression of CB1 receptors was shown to be downregulated 0.7-fold (0.7.+/-0.15, n=12, p<0.01), whereas expression of CB2 receptors was upregulated more than 11-fold (11.6+/-4.5; n=12; p<0.005). Corresponding results were obtained by immunohistochemistry. Blood levels of endocannabinoids were significantly elevated (anandamide 3.5-fold (p<0.001); 2-AG 7-fold (p=0.02)) in patients with CHF, as compared to healthy volunteers. Both CB1 and CB2 receptors are present on healthy human left ventricular myocardium in a balanced distribution. Patients suffering from CHF exhibit a shift of the CB1-CB2 receptor ratio towards expression of CB2 receptors combined with significantly elevated peripheral blood levels of endocannabinoids indicating an activation of the ECS. These results might open up new perspectives regarding the role of endocannabinoid signalling in CHF and its potential as a target for pharmacological modulation., ((c) 2009 Elsevier Ltd. All rights reserved.)

Introduction: Mycotic infection of paranasal sinus could be the etiological factor of chronic sinusitis. The increase in number of fungal sinusitis cases have been reported recently among nonimmunocompromised patient after endodontic treatment of maxillary teeth. Nonspecific clinical signs and incorrect radiologic pictures interpretation as well as loss of therapeutic standards seems to be the cause of false negative diagnosis and difficulties in treatment of fungal sinusitis., Aim of the Study: Clinical and radiological picture of maxillary sinus aspergillosis was described in this paper., Material and Methods: In the period of 2006-2009 in the Department of Maxillo-Facial Surgery 19 patient with fungal maxillary sinusitis was treated. The endodontic treatment of maxillary teeth of the related side was performed previously in 80% examined cases. In 2 cases there were immunocompromised patients with immunosuppressive treatment. In 16 cases patients were referred to our Department due to metallic foreign body of the maxillary sinus. Routine diagnostic radiological imaging was performed in each case: paranasal sinus view--Water's view and panoramic radiograph (orthopantomograph). In 4 cases imaging was extended with computer tomography (CT) visualization. The surgical treatment was performed in each case. The final diagnosis was puted on histopathological examination and fungal culture., Results: In 16 cases of analysed group histopathological examination and fungal culture revealed aspergilosis. In 2 cases fungal culture was negative, but histopathology slices confirm presence of hyphae of Aspergillus. In 1 case the root canal sealer was found in the maxillary sinus. In none case invasive form of aspergillosis was confirmed. In all cases Water's view of paranasal sinuses and ortopantomograph showed partially or totally clouded sinus with well-defined, single or multifocal radiopaque object similar to metallic foreign body. Characteristic finding in CT imaging was well-defined radiodence concretions that have been attributed to calcium deposits in inflammatory changed mucosa, that might suggest "foreign body" picture. In 1 to 3 years follow-up control there was a recurrence of symptoms in one case., Conclusions: Foreign body of maxillary sinus have to be differentiated with aspergilosis. Metallic "foreign body" view in maxillary sinus seems to be characteristic sign of aspergillosis. The most often form of maxillary sinus aspergilosis is aspergilloma.

Aortic recoarctation may be difficult to manage, especially in patients with the need for additional surgical interventions. We describe the case of a 45-year-old man with grown-up congenital heart disease, presenting with recoarctation after initial anatomic repair with a prosthetic graft at the age of 16 years. Further examination revealed heart failure and left ventricular dilation because of severe aortic regurgitation, owing to a bicuspid aortic valve. Through a median sternotomy and CPB, an aortic valve replacement and extra-anatomic ascending-to-descending aortic-bypass-grafting was performed with a posterior pericardial approach. Off-pump coronary artery bypass techniques were applied to reach the descending aorta., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cardiac allograft vasculopathy is a severe complication after heart transplant, and is the major cause of death in patients surviving 1 year after transplant. We present a 59-year-old patient undergoing off-pump, coronary artery bypass surgery, 8 years after heart transplant. Owing to toxic liver disease, the lipid lowering therapy with statins had to be stopped 6 years after transplant, and coronary artery disease developed rapidly within 2 years. Off-pump, coronary bypass surgery was performed using a new, multisuction cardiac positioner; a disposable stabilizer; and a proximal seal system to avoid clamping of the aorta. The patient received 3 bypass grafts: the left internal thoracic artery; to the left anterior descending coronary artery; 1 saphenous vein graft to the marginal branch of the circumflex artery; and 1 saphenous vein graft to the right coronary artery. His postoperative course was uneventful.

The objective of this study was to evaluate long-term outcomes of cardiac transplantation (HTx) in different eras of innovation at a single center during a period of 27 years. We performed a retrospective analysis of 960 cardiac allograft recipients (40 re-HTx) between 1981 and 2008. The results of six different eras based on milestones in HTx were analysed: Era 1: the early years (n = 222,1981-1992); era 2: introduction of inhalative nitric oxide, prostanoids, University of Wisconsin solution (UW) replacing Bretschneider's solution (HTK,n = 118, 1992-1994); era 3: statins (n = 102, 1994-1995); era 4: tacrolimus(n = 115, 1995-1996); era 5: mycophenolate mofetil (MMF, n = 143, 1997-2000) and era 6: sirolimus (n = 300, 2000-2008). Outcome variables weresurvival, freedom from cardiac allograft vasculopathy (CAV) and from acute rejection episodes (AREs). Differences in survival was found comparing era 1 and era 2 with era 4 and era 6 (P < 0.001). Organ preservation through UW demonstrated a significantly better survival as compared with HTK(P < 0.001). Less AREs occurred in patients receiving tacrolimus-sirolimus ortacrolimus-MMF (P < 0.001). Patients receiving tacrolimus-MMF showed less CAV than when treated with cyclosporine-MMF (P < 0.005). There were more ventricular assist device implantations and more re-HTx in era 6 (P < 0.0001)than when compared with other eras. Although the causes for improvement in survival over time are multifactorial, we believe that changes in immunosuppressive therapy have had a major impact on survival.

Objective: Heart-lung transplantation for patients with pulmonary atresia and ventricular septal defect is challenging. The aim of the study was to present a single-center experience with heart-lung transplantation in this difficult group of patients., Methods: A retrospective review identified 9 patients aged 4.1 to 45.6 years (median, 25.4 years) with pulmonary atresia and ventricular septal defect who underwent heart-lung transplantation. Four (44.4%) patients had previous heart operations: 3 of them had palliative procedures (systemic-to-pulmonary shunts), and 1 had multistage correction. A standard transplantation method was used, with the exception of 1 patient with heterotaxy syndrome who underwent a modified operation. Major aortopulmonary collateral arteries were controlled by using various techniques., Results: Follow-up ranged between 2 days and 12.6 years (median, 1.2 years). The hospital mortality rate was 22.2% (n = 2). In the late postoperative period, 3 patients died. The survival curve was similar to that of patients with other diagnoses undergoing heart-lung transplantation. The median length of intensive care unit stay was 58 days (range, 22-82 days), and the median length of hospital stay was 83 days (range, 35-136 days). The most common early complication was bleeding requiring re-exploration. In all cases the bleeding was proved to be from collateral vessels., Conclusions: Heart-lung transplantation in patients with pulmonary atresia and ventricular septal defect requires carefully planned and meticulously performed surgical intervention. This management should be taken into consideration as a future option if the specific anatomy is uncorrectable in early childhood, and the palliative procedures should be avoided.

This prospective study investigates the impact of proton pump inhibitors (PPI) on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline (C(0 h)), 30 min (C(0.5 h)), 1(C(1 h)) and 2 h (C(2 h)) were obtained by high-performance liquid chromatography (HPLC) in 22 patients treated with pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after pantoprazole withdrawal. A four-point limited-sampling strategy was applied to calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with PPI were 2.6 +/- 1.6 mg/L versus 3.4 +/- 2.7 mg/L without PPI (p = ns). Postdose MPA concentrations were lower with PPI at C(0.5 h) (8.3 +/- 5.7 mg/L vs. 18.3 +/- 11.3 mg/L, p = 0.001) and C(1 h) (10.0 +/- 5.6 mg/L vs. 15.8 +/- 8.4 mg/L, p = 0.004), without significant differences at C(2 h) (8.3 +/- 6.5 mg/L vs. 7.6 +/- 3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 +/- 26.6 mg x h/L vs. 68.7 +/- 30.3 mg x h/L; p = 0.003). The maximum concentration of MPA (MPA-C(max)) was lower (12.2 +/- 7.5 mg/L vs. 20.6 +/- 9.3 mg/L; p = 0.001) and the time to reach MPA-C(max) (t(max)) was longer with PPI (60.0 +/- 27.8 min vs. 46.4 +/- 22.2 min; p = 0.05). This is the first study to document an important drug interaction between a widely used immunosuppressive agent and a class of drugs frequently used in transplant patients. This interaction results in a decreased MMF drug exposure which may lead to patients having a higher risk for acute rejection and transplant vasculopathy.

Background: Proton pump inhibitors (PPIs) are often prescribed for gastrointestinal discomfort after heart transplantation (HTx). This study investigates the impact of PPI use on mycophenolate acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus (Tac)., Methods: MPA post-dose plasma concentrations at 0 to 2 hours were obtained by high-performance liquid chromatography (HPLC) in 21 patients on pantoprazole 40 mg/day (PPI group) and 12 patients not on pantoprazole (control group). In a subgroup, MPA plasma concentrations at 0 to 12 hours were measured to evaluate full MPA area-under-the-curve (AUC) measurements., Results: In the PPI group, the mean daily MMF dose was 1,912 +/- 1,023 mg with mean pre-dose serum concentrations (C(0)) of 1.9 +/- 1.4 mg/liter, without a significant difference from controls. Mean post-dose MPA concentrations at 30 minutes (C(0.5h)) were significantly higher in the control group (control, 17.9 +/- 11.5 mg/liter; PPI, 6.7 +/- 4.6 mg/liter; p < 0.001). One- and 2-hour (C(1h, 2h)) MPA concentrations were persistently higher in the control group (1 hour: control, 13.8 +/- 9.1 mg/liter; PPI, 7.7 +/- 4.1 mg/liter; 2 hours: control, 7.6 +/- 4.2; PPI, 5.0 +/- 2.8 mg/liter; p < 0.05). In the subgroup with full AUC measurements, the control group had higher MPA levels 12 hours after dosing (C(12h): control, 3.3 +/- 2.4 mg/liter; PPI, 1.6 +/- 1.3 mg/liter; p < 0.05) and a significantly higher dose-adjusted AUC C(0-3h) (control, 59.5 +/- 20.7 mg/liter; PPI, 41.7 +/- 23.4 mg/liter; p < 0.05). In the subgroup, the maximum plasma concentration of mycophenolic acid (MPA C(max)) in the PPI group was significantly lower (10.1 +/- 4.7 mg/liter) than in the control group (45.5 +/- 53.5 mg/liter, p < 0.0001), whereas t(max) revealed no differences (control: 1.1 +/- 0.77 hours; PPI: 1.1 +/- 0.97 hours). Furthermore, a clear trend for more acute rejection episodes (AREs) and more transplant vasculopathy (TVP) was found in the PPI group., Conclusions: Patients with PPI co-medication show significantly lower MPA plasma concentrations, possibly due to decreased absorption. Therapeutic drug monitoring allows identification of patients with decreased MMF drug exposure who might be at risk for acute rejection.

Primary graft dysfunction after heart transplantation is a severe complication generally related to prolonged ischemia time, size mismatch, or poor quality of the organ. Current therapeutic options include pharmacologic inotropic support with catecholamines or phosphodiesterase inhibitors, and mechanical circulatory support. We report 12 patients who received levosimendan, a new Ca(2+) sensitizer, as adjunctive inotropic support. The patients showed a rapid reduction of the doses of inotropic drugs, and no patient needed mechanical support. Levosimendan may be a useful, adjunctive inotropic drug in the treatment of patients with primary graft dysfunction after heart transplantation.

Background: Major causes of death after heart transplantation are right ventricular pump failure and, chronically, cardiac allograft vasculopathy. Traditional preservation techniques focus on immediate cardioplegia, without particularly considering vascular demands. Recently, the endothelial surface layer, composed of the endothelial glycocalyx and plasma proteins, was discovered to play a major role in vascular barrier function, edema formation, and leukocyte-to-endothelial interaction. The impact of augmenting a traditional preservation solution with plasma colloid albumin was therefore investigated., Methods: Guinea pig hearts underwent cold ischemic storage for 4 hr using Bretschneider's solution (histidine-tryptophan-ketoglutarate [HTK]) without and with augmentation with 1 g% human albumin. After reperfusion, intracoronary adhesion of polymorphonuclear granulocytes, edema formation, left and right heart performance of pressure-to-volume work, and glycocalyx shedding were assessed., Results: Intracoronary retention of leukocytes was doubled in the traditional group (36.4+/-6.6%), whereas it remained at basal values after albumin preservation (23.5+/-2.4%; P<0.05). Addition of albumin to HTK significantly decreased edema formation (wet to dry weight ratio 6.9+/-0.1 vs. 7.2+/-0.2; P<0.05). Although left heart performance was comparable, right heart cardiac output was doubled in hearts having received HTK containing albumin versus HTK alone (94+/-14 vs. 50+/-11 mL/min/g; P<0.05). Glycocalyx shedding was significantly reduced when the hearts were stored under albumin protection., Conclusions: Augmenting HTK with human albumin improves endothelial integrity and heart performance after 4 hr cold ischemia, because of a marked protection of the endothelial glycocalyx. For the prevention of acute and chronic graft failure, the glycocalyx might represent a new target.

Background: The implantation of ventricular assist devices is a well-established procedure for the treatment of imminent heart failure. The exact positioning of the left ventricular apical inflow cannula is crucial, because inflow restrictions might occur when the cannula is placed too close to the interventricular septum or a papillary muscle. We report a novel technique using the Tentacles 3-point fixation device for the exposure of the left ventricular apex during ventricular fibrillation under cardiopulmonary bypass., Methods: We used the Tentacles, a device originally designed for positioning the heart during off-pump coronary artery bypass grafting, for implantation of a biventricular Berlin Heart Excor in a 64-year-old man. The procedure was successful and echocardiographic examinations documented the exact placement of the left ventricular cannula., Results and Conclusion: Our new technique ensures a very precise insertion of apical cannulae, because the left ventricular shape and filling are not impaired.

Background: The clinical relevance of the post-transplant presence of anti-major histocompatibility complex class I chain-related A (MICA) antibodies as a marker for chronic graft failure in heart transplantation was examined using post-transplant sera from 159 heart transplant recipients. Mean follow-up after transplantation was 7 +/- 4.9 years., Methods: The sera were screened by Luminex (Luminex Corp, Austin, TX) for MICA antibodies. Samples that tested positive were confirmed using a Luminex MICA single-antigen bead assay. The antigen specificity of the detected antibodies was identified. Outcome parameters were survival, cardiac allograft vasculopathy (CAV), and cellular rejection., Results: We retrospectively selected 159 patients: 107 with 0 or 1 rejection and 52 with 2 or more acute rejection episodes, of whom 36 (22.6%) had a positive screen for anti-MICA antibodies. In 19 of 36 samples, specific anti-MICA antibodies were confirmed by single antigen assay. The presence of post-transplant specified anti-MICA antibodies in patients' sera was associated with acute rejection (63.2% vs 28.6%, p < 0.01) and CAV (78.9% vs 32.8%, p < 0.01). Multivariate analysis identified anti-MICA positivity as an independent risk factor for the development of CAV., Conclusions: The results indicate that anti-MICA antibodies may be related to adverse outcome after heart transplantation. Post-transplantation monitoring of anti-MICA antibodies could identify patients with an increased risk for acute rejection and vasculopathy.

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.

Mutations in nicotinic receptor subunits have been identified in some families with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Normal intelligence has currently been considered the rule, although anecdotal cases with intellectual disability have been reported. We aimed to evaluate the frequency and degree of neuropsychological disorders in ADNFLE associated with nicotinic receptor mutations by testing 11 subjects from four families with a comprehensive neuropsychological assessment. General intellectual function was below the normal range in 45% of the subjects. All were abnormal in one or more executive task. Memory was either more affected than executive functions or equally affected in two thirds of subjects, suggesting a frontotemporal pattern of cognitive impairment. Cognitive dysfunction appears to be an integral part of the broad phenotype of ADNFLE with nicotinic receptor mutations, a fact that has been underestimated until now. The cognitive disorder affects executive functions as well as memory in most subjects.

Homocysteine (Hcy) is a thyol amino acid resulting from demethylation of methionine. It is metabolized through two pathways: remethylation and trassulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia (hHcy) is a risk factor for cerebrovascular disease, dementia, inborn defects, impaired cognitive function. Several drugs may change metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. HHcy has been documented in epileptic patients after chronic treatment with antiepileptic drugs (carbamazepine, valproate). HHcy may lead to increase of the level of asymmetric dimethylarginine (ADMA). ADMA has been identified as a potential risk factor for cardiovascular disease and endothelial dysfunction. ADMA is a product of methylation of L-arginine and endogenous nitric oxide (NO) synthase inhibitor, and regulator of NO production. NO plays a role in the convulsant effect. Supplementation of B vitamins, folate and L-arginine is a strategy to reduce Hcy levels in patients with epilepsy treatment antiepileptic drugs.