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Background: The ideal timing of a durable assist device implantation in patients with end-stage heart failure presenting with INTERMACS profile I is still controversial. The data on extracorporeal life support (ECLS) bridge to durable left ventricular assist device (LVAD) in these patients is limited. Materials and methods: We retrospectively analyzed the outcomes of 35 patients in acute cardiogenic shock (CS) who, between December 2013 and September 2020, were bridged with ECLS to durable LVAD. The mean age was 52.3 ± 12.0 years. The primary endpoints of this study were in-hospital, 30-day, 6-month, and 1-year mortality. The secondary endpoint was the development of any postoperative adverse events and other characteristics during the follow-up period. We also assessed the impact of the rescue ECLS on the recovery of the end-organ function. Results: In-hospital, 30-day, 6-month, and 1-year survival was 65.6%, 75.9%, 69.2%, and 62.7% respectively. The median time on ECLS was 7 days (IQR 5.0–13.0). We observed a high incidence of a severe right heart failure (22.9%), acute kidney injury on dialysis (68.6%), and respiratory failure (77.1%). Bridge with ECLS provided a significant recovery of liver and kidney function prior to durable LVAD implantation. Conclusion: The concept of bridging patients presenting in end-stage heart failure and cardiogenic shock with ECLS prior to durable LVAD implantation is a feasible method to ensure acceptable survival rates and significant recovery of the end-organ function.

BACKGROUND: The use of left ventricular assist devices (LVAD) in patients with advance heart failure is still associated with an important risk of immune dysregulation and infections. The aim of this study was to determine whether extracorporeal blood purification using the CytoSorb device benefits patients after LVAD implantation in terms of complications and overall survival.MATERIALS AND METHODS: Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation, of whom 72 underwent CytoSorb therapy and 135 did not. Overall survival, major adverse events, and laboratory parameters were compared between 112 propensity score-matched patients (CytoSorb: 72 patients; non-CytoSorb: 40 patients).RESULTS: WBC (p = .033), CRP (p = .001), and IL-6 (p < .001), significantly increased with LVAD implantation, while CytoSorb did not influence this response. In-hospital mortality and overall survival during follow-up were similar with CytoSorb. However, patients treated with CytoSorb were more likely to develop respiratory failure (54.2% vs. 30.0%, p = .024), need mechanical ventilation for longer than 6 days post-implant (50.0% vs. 27.5%, p = .035), and require tracheostomy during hospitalization (31.9% vs. 12.5%, p = .040). No other significant differences were observed with regard to major adverse events during follow-up.CONCLUSIONS: Overall, our results showed that CytoSorb might not convey a significant morbidity or mortality benefit for patients undergoing LVAD implantation.

Background: There is an ongoing debate about the influence of the female gender on postoperative outcomes after durable left ventricular assist device (LVAD) implantation. Despite the differences in pathophysiology of heart failure in females, therapy concepts are the same as in the male population. The aim of this study was to investigate the role of the female gender in surgical heart failure therapy. Materials and methods: Between August 2010 and January 2020, 207 patients were treated with durable LVAD at out institution. We matched 111 patients in two groups to compare the outcomes in male and female patients and to stratify the risk factors of mortality. Results: The groups were matched 2:1 and were comparable after matching. We found no difference in in-hospital and follow-up mortality between male and female patients. Postoperative adverse events and complications were found to be unvaried across male and female patients. Female patients had higher rates of postoperative LVAD-thrombosis compared to their male counterparts (13.5% vs 0, p = 0.001) and the rates of renal replacement therapy lasting over 90 days were also higher in the female group (33.8% vs 56.8%, p = 0.021). Furthermore, the female gender was not an independent predictor neither of in-hospital nor follow-up mortality. Conclusions: Durable continuous flow left ventricular assist devices as a bridge to transplantation or recovery in female patients are associated with a higher risk of acute kidney injury requiring RRT and are at a higher risk of LVAD-thrombosis. Nevertheless, survival rates between genders are similar.

Purpose Ex vivo lung perfusion is an innovative technique to evaluate marginal lung organs especially after DCD. Normothermic continuous perfusion should reduce ischemic damage and improve the outcome of lung transplantation. However, the optimal protocol for EVLP has not been defined so far. The aim of our study was to compare cytokine/chemokine concentrations in perfusion solutions using different kinetics and solution compounds of EVLP in a porcine cardiac arrest model and to correlate the inflammatory parameters to oxygenation capacity values (∆pO2). Methods Following cardiac arrest and 1h of warm ischemia, lungs were harvested and flushed. Groups were processed as immediate (I-EVLP) 1h cold static preservation (CSP) and delayed (D-EVLP; 9h CSP). D-EVLP lungs were perfused with different solutions: Steen vs. modified Custodiol-N containing dextran (CD) or dextran/albumin (CDA). Cytokine/chemokine levels were analyzed at baseline (0h), after 1h, 4h using multiplex protein arrays. Results Concentrations of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α and IL-1β increased significantly (p Conclusion In a non-heart beating porcine cardiac arrest model with relevant IRI, lungs were perfused with normothermic EVLP. Longer CSP prior to EVLP did not result in enhanced cytokine secretion, but the first hours of reperfusion seem crucial for tissue damage. CD-solution dampens the cytokine/chemokine secretion probably by iron chelators and, possibly, protecting effects of dextran. Addition of albumin had no further effect on inflammation. Cytokine/chemokine concentrations correlated negatively with the oxygenation capacity, an important parameter for organ acceptance. These finding may help to optimize the ex vivo preservation procedure and possibly, more organs could reach the clinically relevant threshold for transplantation, thus, the pool of marginal donor lungs could be enlarged.

The use of left ventricular assist devices (LVADs) for advanced heart failure is becoming increasingly common. However, optimal timing and patient selection remain controversial. The aim of this study was to investigate outcomes of LVAD implantation for advanced heart failure in critically ill patients (INTERMACS 1 and 2). Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation. Overall survival, major adverse events, and laboratory parameters were compared between patients in INTERMACS 1-2 (n = 107) and INTERMACS 3-5 (n = 100). Preoperative white blood cells, C-reactive protein, procalcitonin, bilirubin, alanine transaminase, and lactate dehydrogenase were all significantly higher in INTERMACS 1-2 when compared to INTERMACS 3-5 (P < .05). During hospitalization following LVAD implantation, patients in INTERMACS 1-2 were more likely to develop major infections (41.1% vs. 23.0%, P = .005), respiratory failure (57.9% vs. 25.0%, P < .001), mild (20.6% vs. 8.0%, P = .010), and moderate (31.8% vs. 7.0%, P < .001) right heart failure, and acute renal dysfunction (56.1% vs. 6.0%, P < .001). During a median follow-up of 2.00 years (interquartile range (IQR) 0.24-3.39 years), they had a higher incidence of thoracic (15.9% vs. 4.0%, P = .005) and gastrointestinal bleeding (21.5% vs. 11.0%, P = .042), as well as right heart failure (18.7% vs. 1%, P < .001). Risk of death was significantly higher in the INTERMACS 1-2 group (hazards ratio (HR) 1.64, 95% CI 1.12-2.40, P = .011). LVAD implantation in critically ill patients is associated with increased morbidity and mortality. Our results suggest that decision for LVAD should be not be delayed until INTERMACS 1 and 2 levels whenever possible.

Background and Objectives: The understanding of high body mass index (BMI) and outcomes after Left Ventricular Assist Device (LVAD) implantation continues to evolve and the relationship has not been established yet. In this study, we investigated the effects of obesity (BMI &gt, 30 kg/m2) on post&ndash, LVAD implantation outcomes. HeartWare LVAD and Heart Mate III LVAD were implanted. The primary outcome that was measured was mortality (in-hospital and on follow-up). The secondary outcomes that were measured were major adverse events. Materials and Methods: At our institution, the West German Heart and Vascular Center (Essen, Germany), from August 2010 to January 2020, a total of 210 patients received a long-term LVAD. Patients were stratified according to BMI &ge, 30 kg/m2 representing the obesity threshold. The first group (n = 162) had an average BMI of 24.2 kg/m2 (&plusmn, 2.9), and the second group (n = 48) had an average BMI of 33.9 kg/m2 (&plusmn, 3.2). Baseline demographics were analysed alongside comorbidities per group. Results: Overall mortality was not significantly different between the obese group (51.1% n = 24) and the nonobese group (55.2%, n = 85) (p = 0.619). The difference between the mean duration of survival of patients who expired after hospital discharge was insignificant (2.1 years &plusmn, 1.6, group 1, 2.6 years &plusmn, 1.5, group 2, p = 0.29). In-hospital mortality was unvaried between the two groups: group 1: n = 34 (44% out of overall group 1 deaths), group 2: n = 11 (45.8% out of overall group 2 deaths) (p &gt, 0.05). Postoperative complications were unvaried between the obese and the non-obese group (all with p &gt, 0.05). However, a significant difference was found with regards to follow-up neurological complications (18.5% vs. 37.8%, p = 0.01) and LVAD thrombosis (14.7% vs. 33.3%, p = 0.01), as both were higher in the obese population. Conclusion: Obesity does not form a barrier for LVAD implantation in terms of mortality (in-hospital and on follow up). However, a significantly higher incidence of follow-up LVAD thrombosis and neurological complications has been found in the obese group of patients.

Background: The low acceptance rates in lung transplantation underline the importance to use every potential transplantable organ. With the use of normothermic ex vivo lung perfusion (EVLP) there is a potential to use more donor lungs for transplantation. Aim of this study was to evaluate if EVLP has an effect on cytomegalovirus (CMV) infection after lung transplantation. Methods: Between May 2016 and October 2018, 57 lung transplants were performed. Out of these 21 extended criteria lungs were evaluated by EVLP and 16 transplanted. In a retrospective study, results of EVLP treated lungs were compared with lungs after cold storage preservation (CSP). Donor/recipient CMV IgG status and seroconversion rate was examined. Results: Donors were CMV IgG+ in EVLP 69% and CSP 61% (n.s.). Best pO2 on procurement at FiO2 1.0 was in EVLP 278±76 versus CSP 413±96 mmHg (P≤0.05). Recipients were CMV IgG+ in EVLP 38% and CSP 63% (P

Background Resternotomy in cardiac surgery is considered a risk factor for postoperative complications. Previous studies have demonstrated an ambiguous relationship between resternotomy and clinical outcomes. Registry data from a mixed population of durable circulatory support devices suggest that history of cardiac surgery is a risk factor for mortality. Our study investigates the prognostic significance of resternotomy in a homogenous cohort of left ventricular assist device (LVAD) recipients. Methods The study included adult patients receiving a continuous-flow LVAD at our institution during the period 2010–2016. Postoperative adverse events and length of stay were analyzed. Survival was assessed at 6 months and by the end of the study. Multivariate risk factor analysis was conducted for independent predictors of death. Results One hundred twelve patients, who received an intrapericardial LVAD (HVAD, HeartWare), were included in our analysis. Twenty-four patients (21.4%) had a history of previous sternotomy. These patients were older and non-eligible for bridging, and had more frequently coronary heart disease. Univariate analysis demonstrated no differences in the observed complications postoperatively. Survival was similar among groups. Destination therapy was the only predictor of mortality in our analysis (p = 0.02). Conclusions Resternotomy was not associated with worse outcomes after LVAD implantation in our cohort.

In Deutschland werden nur 40–50 % der Lungen von Multiorganspendern transplantiert. Daher ist es von besonderer Bedeutung, moglichst jedes potenziell transplantable Spenderorgan zu verwenden. Mit dem Verfahren der normothermen Ex-vivo-Lungenperfusion (EVLP) besteht die Moglichkeit, Spenderlungen genauer zu evaluieren, die zuvor als nichttransplantabel eingestuft wurden. Das Verfahren der normothermen, azellularen EVLP wird detailliert beschrieben. Dabei wird ausfuhrlich auf die praktische Handhabung eingegangen. Seit Januar 2016 wurden im Westdeutschen Lungenzentrum 56 Lungentransplantationen durchgefuhrt. Elf initial nicht den Standardkriterien entsprechende Spenderlungen wurden mithilfe der EVLP evaluiert und 9 davon transplantiert. Entsprechend dem Toronto-Protokoll wurden die Lungen fur 4 h konditioniert; vor der Lungentransplantation (LuTx) sollte die Differenz des Sauerstoffpartialdruckes (Δ pO2/FIO2-Wert) zwischen arterieller und venoser Perfusionslosung >350 mmHg betragen. In einer retrospektiven Analyse wurden Spender- und Empfangerdaten, Organperfusionsdaten und der postoperative Verlauf untersucht. Das mittlere Spenderalter (Jahre) war fur LuTx 54 ± 14 und 51 ± 8 fur non-LuTx (nichtsignifikant, n. s.). Vor Entnahme betrug der Sauerstoffpartialdruck (pO2) bei einer inspiratorischen Sauerstofffraktion (FIO2) von 1,0: LuTx 324 ± 72 mmHg vs. non-LuTx 382 ± 88 mmHg (n. s.). Die Beatmung der Spender dauerte: LuTx 104 ± 44 h, non-LuTx 245 ± 180 h (n. s.). Der ∆ pO2/FIO2-Wert nach 4 h wurde fur LuTx mit 389 ± 49 mmHg und fur non-LuTx mit 254 ± 0 mmHg bestimmt (n. s.). Die „Out-of-body“-Zeit nach Implantation der zweiten Lunge betrug 724 ± 133 min. Die postoperative Beatmungsdauer umfasste 232 ± 305 h und der Intensivstationsaufenthalt 274 ± 293 h. Die Dreisigtagesterblichkeit wurde mit 9 % berechnet. Die normotherme EVLP kann als sicheres Verfahren zur Evaluation initial nichttransplantabler Spenderlungen verwendet werden. Diese Erfahrungen eines Einzelzentrums zeigen, dass eine Verwendung von 81 % der zunachst als nichttransplantabel eingestuften Spenderlungen moglich ist. Die perioperativen Ergebnisse sind mit denen der Standardtransplantation vergleichbar.

Purpose After successful lung transplantation, patients can potentially reach same strength and endurance as healthy individuals. Although high-altitude trekking has been reported after LuTX, data on the patient's physiological adaptation during prolonged exercise in a reduced oxygen environment remains scarce. Methods In September 2019, 14 lung transplanted patients and their accompanying doctors, climbed Mount Jebel Toubkal (4167 m; 13 671 ft), the highest peak in North Africa, High Atlas, Morocco. Participants had regular cardiopulmonary exams (lung function, polysomnography, echocardiography) as well as blood sampling (capillary blood gasses, lactate, creatinine) throughout the expedition up to 3145 m (10 318 ft). Results Patients (♀: n=3 | ♂: n=11) had a median age of 42.1 years (24.8-65.2). Their underlying diagnoses were CF (n=10), Emphysema (n=2), IPF (n=1) and PH (n=1). Median time from LuTX to this expedition was 4.1 Years (1.7-17.6). Controls (♂: n=4) were 31.3 (29.3-46.7) years old. Over 7 days, participants hiked a distance of 81km (50.3 mi) with a cumulative elevation gain of 5496 m (18,031 ft.) vertical distance. Eleven Patients (78.6%) reached the summit whereas three patients had to abort because of altitude sickness (n=1 on day 1 at 2431m) or physical exhaustion (n=2 on day 3 at 3124m and day 6 at 3800m). Blood gas analysis and vital signs did not differ significantly between the patients and four healthy controls (pO2: 59.1 ±8.9 vs. 61.8 ±14.4 mmHg | pCO2: 29.8 ±1.5 vs. 29.8 ±0.5 mmHg | lactate 0.82 vs 0.83 mmol/l). Creatinine was significantly higher in transplanted patients (1.87 vs. 0.97 mg/dl; p=0.025). Conclusion Although technically challenging, medical monitoring of lung transplanted patients is feasible during high altitude hiking. In carefully selected athletic LuTX patients, gas exchange and metabolism didn't differ compared to healthy adults.

Left ventricular assist devices (LVAD) became a routine instrument in the treatment of severe heart failure with constantly increasing number of patients treated with LVAD (1). Continuous technical development and large empirical knowledge in this field has led to a very high reliability and excellent long-term results (MOMENTUM III). Recently published results for the first time reported even better 2-year survival in LVAD compared to heart transplantation (HTx) (2). However, there is an inevitable risk of device failure alongside which may result in the need for device exchange. Mainly three causes are associated with the need for exchange, specifically (in the order of frequency) (I) device thrombosis, (II) infection and (III) device malfunction.

Acute kidney injury (AKI) is frequent in patients scheduled for implantation of a left ventricular assist device (LVAD) and associated with increased mortality. Although several risk models for the prediction of postoperative renal replacement therapy (RRT) have been developed for cardiothoracic patients, none of these scoring systems have been validated in LVAD patients. A retrospective, single center analysis of all patients undergoing LVAD implantation between September 2013 and July 2016 was performed. Primary outcome was AKI requiring RRT within 14 days after surgery. The predictive capacity of the Cleveland Clinic Score (CCS), the Society of Thoracic Surgeons Score (STS), and the Simplified Renal Index Score (SRI) were evaluated. 76 patients underwent LVAD implantation, 19 patients were excluded due to preoperative RRT. RRT was associated with a prolonged ventilation time, length of stay on the ICU and 180 day mortality (14(60.9%) vs 6(17.6%), P < .01). Whereas the Thakar Score (7.43 ± 1.75 vs 6.44 ± 1.44, P = .02) and the Mehta Score (28.12 ± 15.08 vs 21.53 ± 5.43, P = .02) were significantly higher in patients with RRT than in those without RRT, the SRI did not differ between these groups (3.96 ± 1.15 vs 3.44 ± 1.05, P = .08). Using ROC analyses, CCS, STS, and SRI showed moderate predictive capacity for RRT with an AUC of 0.661 ± 0.073 (P = .040), 0.637 ± 0.079 (P = .792), and 0.618 ± 0.075 (P = .764), respectively, with comparable accuracy in the Delong test. Using univariate logistic regression analysis, only the De Ritis Ratio (OR 2.67, P = .034) and MELD (OR 1.11, P = .028) were identified as predictors of postoperative RRT. Risk scores which are predictive in general cardiac surgery cannot predict RRT in patients after LVAD implantation. Therefore, it seems to be necessary to develop a specific risk score for this patient population.

Background: The prognostic utility of B-type natriuretic peptide (BNP) in heart failure is well recognized. Previous studies demonstrated that BNP levels decrease after left ventricular assist device (LVAD) implantation. We sought to investigate the predictive value of baseline and changes in BNP levels in LVAD recipients. Methods: BNP was measured in baseline and follow-up plasma samples from consecutive patients receiving a continuous-flow LVAD from 2010 through 2016. Absolute values and changes from baseline were related to clinical outcomes. Results: Median BNP at baseline was 885 [interquartile range (IQR): 450-1,624] pg/mL, decreasing to 289 (IQR: 154-534) pg/mL at 90 days after LVAD implantation. Cox regression analysis revealed that higher baseline and follow-up BNP levels were not associated with increased risk of death at 180 days (P=0.12 and P=0.32, respectively). In the univariate analysis 90-day BNP, but not baseline BNP, was significantly associated with the combined death/hospitalization outcome 180 days after LVAD implantation [hazard ratio (HR) 1.03, 95% CI: 1.01-1.06; P=0.006]. This significance was not preserved after adjusting for multiple covariates (HR 1.01, 95% CI: 0.98-1.04; P=0.62). At 90 days, there was no BNP lowering in 20.6% of subjects. This was not associated with higher risk for death or the composite of death/hospitalization (P=0.11 and P=0.06 respectively). Conclusions: BNP absolute levels and changes from baseline are not independently associated with clinical outcomes after LVAD-implantation. These findings suggest an impaired prognostic performance of BNP after LVAD implantation. CA Papathanasiou

Objectives: Increasing incidence of end-stage heart failure has moved the therapy with left ventricular assist devices to the forefront of surgical treatment. Moreover, continuous sophistication in this technology has resulted in increasing proportion of patients on prolonged support. Early and late complications after left ventricular assist device as a bridge to transplantation and present factors associated with long-term support and long-term outcomes of patients supported for at least 1 year were compared. Methods: A total of 163 consecutive patients who underwent left ventricular assist device implantation as bridge to transplantation were included. A total of 79 patients were supported for at least 1 year (long-term support), whereas 84 patients were supported for less than 1 year (short-term group). Results: Factors associated with a successful long-term support were male gender (p Conclusion: Prolonged left ventricular assist device support as bridge to transplantation is associated with lower mortality and lower incidence of device failure requiring device exchange. However, long-term support reduces the chance of device explantation for myocardial recovery and increases the incidence of higher-grade aortic regurgitation in the follow-up.

Purpose Ex vivo lung perfusion (EVLP) offers a unique potential in evaluation, optimization and transplantation of lungs that would otherwise potentially be rejected. Between 2016 and 2020 208 lung transplants (LuTx) were performed and 22 donor lungs were evaluated by EVLP of which 16 were transplanted. Aim of the study was to compare mid-term results in LuTx recipients with or without the use of EVLP. Methods In a retrospective single-center analysis data from a prospectively collected database were analysed. The EVLP group (n=16) consisted of donor lungs classified as marginal and were evaluated by EVLP and afterwards transplanted. The non EVLP group (n=16) consisted of conventional LuTx recipients matched for age and pulmonary disease. Both groups were compared for the endpoints survival, primary graft dysfunction, rejection episodes and chronic allograft dysfunction. Results Recipient age was 55 ± 6 years in EVLP group and 57 ± 5 years non EVLP group (n.s.). Female gender was present in 36% EVLP patients and 50% non EVLP (n.s.). The rate PGD grade 1 at 72 h post-LTx was 14% in both groups (each2/16). In non EVLP group 1recipient was PGD 2 (7%). PGD3 was present only in the EVLP group 14% (2/16) vs. 0% in control. At last visit, post-LuTx, forced expiratory volume in 1 s (FEV1%) as percentage of predicted best was similar in the EVLP and non-EVLP group (77% vs. 78%). Chronic lung allograft dysfunction was diagnosed in one non EVLP patient and one EVLP patient during follow up post-LuTx. In the EVLP group 2 patients had rejection episodes subjected to treatment and 6 patients in the non EVLP group (n.s.). Survival at 1 year was 81% for the EVLP group and 94% in non EVLP group (n.s.). Conclusion Recipients transplanted with extended criteria donor lungs, thoroughly evaluated by EVLP show similar mid term outcomes as conventionally transplanted lungs from standard donors. EVLP shall increase the number of acceptable donor lungs. Future clinical trials will bring further evidence; clear guidelines regarding application of machine perfusion have to be developed.

Purpose Heart Transplantation (HTX) is an established therapy for endstage Heart Failure with excellent long term results. However, shortage of donor organs leads to increased use of extended criteria organs and rising numbers of high risk recipients on the high-urgency list and on mechanical circulatory support (MCS). Donor organ machine perfusion (MP) allows continuous warm perfusion of the beating heart, thus reducing time of ischemia as well as allowing for standardized evaluation. AIM: analyze outcome of HTX using donor heart MP. Methods In a retrospective single-center study, data from a prospectively collected database were analyzed. From July 2018 to September 2020, eleven hearts were retrieved and perfused using the Organ Care System (OCS), 9 hearts were transplanted. Criteria to use the OCS were 1) estimated ischemic time > 4 hours for any reason, 2) inotropes > 0.25 µg/kg/min, 3) LV-EF Results All patients survived the procedure and the 30-day interval [time since HTX 8-799 d]. No MP related complications were noted. One patient died after 233 days due to sepsis. 4 patients were on temporary ECLS support in the early postoperative period (6-12d) due to initial right ventricular dysfunction. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsies showed no rejection or mild rejection 1R in two cases (21d and 3 months surveillance biopsy). Two donor hearts were rejected after OCS perfusion 1) because of previously unknown coronary artery disease (angiography on OCS) and 2) due to underestimated aortic valve insufficiency and severe septum hypertrophy. Conclusion Ex vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options may increase the number of acceptable donor hearts and improve results. Future clinical trials will bring further evidence, clear guidelines regarding application of MP have to be developed.

Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

Limited data are available about lung transplantation (LTx) from donors suffering cardiac arrest (CA) prior to actual donation.A retrospective analysis of LTx performed between January 2007 and September 2012 was done with the focus on CA in donors. The recipients were grouped depending on the history of donor CA and CA duration (downtime) as: No cardiac arrest ("NoCA"), CA downtime less than 20 min ("CA20"), and CA downtime equal to or more than 20 min ("CA20"). Early and mid-term outcomes after LTx were compared among the three groups.A total of 237 LTx were performed during the study period. One hundred eighty-eight patients received organs from "NoCA" donors, 25 from "CA20" donors, and 24 patients from "CA20" donors. There was a trend toward better overall cumulative survival in both CA groups (log rank p = 0.076) whereas the survival in the "CA20" group was significantly better than in the "NoCA" group in the subgroup analysis (log rank p = 0.045). Freedom from bronchiolitis obliterans syndrome (BOS) also increased with increase in CA duration, although it did not reach statistical significance.Transplantation of lungs from donors with a history of CA is safe and feasible. Longer duration of cardiac arrest may improve the outcomes after the LTx in terms of survival and freedom from BOS.

Purpose Ex Vivo Lung Perfusion (EVLP) is a promising tool for evaluation and reconditioning in marginal donor lungs. However, the optimal protocol is discussed controversially. It is our hypothesis that different EVLP protocols and different perfusion solutions result in different cytokine patterns during EVLP. Methods Following cardiac arrest and 30 min of no-touch warm ischemia, pig lungs were harvested, flushed and stored in cold preservation solutions. Different groups were processed as immediate long EVLP (I-EVLP, 12 h), delayed short EVLP (4 h) after 9 hours of cold storage (D-EVLP). Lungs were perfused with different acellular solutions: Steen solution or modified HTK solution containing either dextran(CD) or dextran and albumin (CDA). Pulmonary gas exchange, biochemical and structural parameters were recorded hourly. Cytokine / chemokine levels were analyzed in perfusates at baseline and after 1 and 4 h of EVLP. Results ∆ pO2 (pulmonary venous - pulmonary arterialpO2) was higher in D-EVLP group, especially at h 1: I-EVLP: 259 ± 132, D-EVLP: 291 ± 96 and h 2: I-EVLP: 228 ± 125, D-EVLP: 252 ± 116 (n.s.). Compared to D-EVLP, lungs that underwent EVLP with CD and CDA showed significantly higher oxygen capacity (∆ pO2 CD: 402.79 +30.33 mmHg, CDA: 414.86 + 9.77 mmHg). Within 4 h ELVP, concentrations of IFN-γ, TNF-a, IL-1α/β, IL-10, CXCL8 (IL-8) and IL-18 increased significantly (all p Conclusion In a non-heart beating porcine lung donor model with relevant ischemic tissue damage, lungs were perfused with normothermic EVLP. Even after 9 hours cold static preservation (CSP) and 4 hours EVLP lung, function is comparable to direct EVLP. The modified HTK solution with dextran and dextran/ albumin had significantly better oxygenation. Cytokines and chemokines including the cell death marker IL-18 increase during 4 h of EVLP but a delay before EVLP may not dramatically worsen the inflammatory response.

Objective: To enlarge the donor pool for lung transplantation, an increasing number of extended criteria donor lungs are used. However, in more than 50% of multi-organ donors the lungs are not used. Ex vivo lung perfusion offers a unique possibility to evaluate and eventually recondition the injured donor lungs. The aim of our study was to assess the enlargement of the donor pool and the outcome with extended criteria donor lungs after ex vivo lung perfusion. Patients and Methods: Data were prospectively collected in our lung transplant database. We compared the results of lung transplants after ex vivo lung perfusion with those after conventional cold static preservation. In total, 11 extended criteria donor lungs processed with ex vivo lung perfusion and 41 cold static preservation lungs transplanted consecutively between May 2016 and May 2017 were evaluated. Normothermic ex vivo lung perfusion was performed according to the Toronto protocol for 4 h. Cold static preservation lungs were stored in low-potassium dextran solution. Results: Ex vivo lung perfusion lungs before procurement had significantly lower PaO2/FiO2 (P/F) ratios and more X-ray abnormalities. There were no statistically significant differences for pre-donation ventilation time, smoking history, or sex. After reconditioning with ex vivo lung perfusion, 9 out of 11 processed lungs were considered suitable and successfully transplanted. The mean postoperative ventilation time and in-hospital stay were not significantly different in ex vivo lung perfusion and cold static preservation recipients. Conclusion: Ex vivo lung perfusion can safely be used in the evaluation of lungs initially considered not suitable for transplantation. The primary outcome was not negatively affected and normothermic ex vivo lung perfusion is a useful tool to increase the usage of potentially transplantable lungs.

Objectives Lung transplantation (LTx) remains the definitive treatment for end-stage lung failure, whereas chronic obstructive pulmonary disease (COPD) represents one of the main diagnoses leading to the indication for a transplant. We sought to assess long-term outcomes after LTx in patients diagnosed with COPD and analyze factors influencing outcome in this frequent patient cohort. Methods Between January 2007 and November 2013, a total of 88 LTx were performed in patients with COPD in our institution. Patients with emphysema associated with alpha1-antitrypsin deficiency were excluded from this observation. The study design was a retrospective review of the prospectively collected data. A large number of pre-, intra-, and postoperative variables were analyzed including long-term survival and freedom from bronchiolitis obliterans syndrome (BOS). Furthermore, impact of different variables on survival was analyzed. Results Preoperative donor data indicated a large proportion of marginal donors. While the overall cumulative survival after six yr was 57.4%, the results in terms of BOS-free survival in long-term follow-up were 39.7% after six yr. Patients with COPD were also associated with a low incidence (2.3%) of the need for postoperative extracorporeal life support (ECLS). Conclusions Long-term results after LTx in patients with COPD are acceptable with excellent survival, freedom from BOS, and low use of ECLS postoperatively despite permanently increasing proportion of marginal organs used.

Objectives Post-cardiotomy cardiogenic shock (PCCS) results in substantial morbidity and mortality, whereas refractory cases require mechanical circulatory support (MCS). The aim of the study was to compare extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs) utilized in the management of PCCS. Methods In total, 56 consecutive patients who developed PCCS from 2005 to 2014 required MCS as a bridge to decision-24 were supported with a VAD and 32 with an ECMO. Groups were compared with respect to pre- and intraoperative characteristics and early and long-term outcomes to evaluate the impact of the type of MCS on complications and survival. Data are mean ± standard deviation and median with quartiles. Results EuroSCORE II was significantly higher in the VAD group than in the ECMO group (28 ± 20 vs 13 ± 16, P = 0.020) corresponding to significantly higher New York Heart Association (P = 0.031) class and Canadian Cardiovascular Society class (P = 0.040) in the cohort. The median duration of support was 10 (4-23) and 7 (4-10) days in the VAD and ECMO groups, respectively. There were no significant differences in ITU (P = 0.262), hospital stay (P = 0.193) and incidences of most postoperative complications. A significantly higher proportion of patients was successfully weaned/upgraded in the VAD group [13 (54%) vs 4 (13%), P = 0.048] with a trend towards higher discharge rate [9 (38%) vs 5 (16%), P = 0.061]. Overall cumulative survival in early follow-up [Breslow (Generalized Wilcoxon) P = 0.017] and long-term follow-up [Log-rank (Mantel-Cox) p = 0.015] was significantly better in the VAD group. Conclusions VAD and ECMO represent essential tools to support patients with PCCS. Our preliminary results might indicate some benefits of using VAD in this group of patients; however, this evidence should be further assessed in larger multicentre trials.

OBJECTIVES The presence of bacterial colonization that causes chronic pulmonary infections in cystic fibrosis (CF) patients remains a key issue before lung transplantation. We sought to assess the impact of intraoperative taurolidine lavage on bacterial colonization and long-term outcomes following lung transplantation in CF patients. METHODS Between 2007 and 2013, 114 CF patients underwent lung transplantation at our institute, and taurolidine 2% bronchial lavage was applied in a substantial proportion of patients (n = 42). A detailed analysis of donor and recipient bacterial colonization status in treatment and control groups and their impact on outcome was performed. RESULTS The proportion of recipients colonized with Pseudomonas aeruginosa was lower in the taurolidine group at 3 months (P

Objectives Preoperative liver dysfunction is a well-known risk factor for adverse events after major surgery. However, there is only little data regarding the precise role of the Model of End-Stage Liver Disease (MELD) score and the De Ritis ratio (DRR, alanine transaminase/aspartate aminotransferase) as a predictor for outcome after left ventricular assist device (LVAD) implantation. Methods A retrospective analysis of all patients undergoing LVAD implantation at our institution between January 2012 and August 2014 was performed. The primary outcome was survival at 180 days after surgery. Results During the observation period, 63 patients underwent LVAD implantation (mean age 59.9 ± 8.3 years, 50% male). Mean preoperative ejection fraction was 16.3 ± 7.7, 13 patients required preoperative renal replacement therapy and 9 patients were on extracorporeal life support. Mean Interagency Registry for Mechanically Assisted Circulatory Support level was 2.8 ± 1.3, mean preoperative MELD was 12.7 ± 7.2, mean preoperative DRR was 2.01 ± 4.4. Aspartate aminotransferase (102 ± 220.8 vs 57.8 ± 123.4 U/l, P = 0.041), MELD score (16.1 ± 8.8 vs 11.4 ± 6.1, P = 0.017) and DRR (4.2 ± 7.8 vs 1.1 ± 1.1, P = 0.001) were significantly higher in non-survivors than in survivors after 180 days. Using logistic regression analyses, a DRR >1.37 was an independent predictor for 30-day mortality [odds ratio (OR) 4.5] and 180-day mortality (OR 4.1). In addition, the DRR was associated with postoperative acute kidney injury with need for renal replacement therapy (OR 4.2) and prolonged postoperative ventilation time >72 h (OR 3.8). Using receiver operator characteristics analyses, DRR showed a sensitivity of 0.80 and a specificity of 0.81 (area under the curve 0.834, cut-off 1.37) for 180-day mortality. Conclusions The DRR is predictive of early and mid-term mortality as well as relevant morbidities in patients undergoing LVAD implantation. Therefore, the DRR should be considered within the preoperative risk stratification and patient selection for LVAD implantation.

Purpose Although lung transplantation and lung volume reduction (both surgically and endoscopically: LVRS/ELVR) are well established therapies for end-stage emphysema patients, data on LVR prior to LuTX remains scarce. Thus, we aim to analyze the impact of pre-transplant LVR on post-LuTX outcomes. Methods From 1/2015 to 5/2018, 55 patients underwent bilateral LuTX for COPD and α1-AT deficiency at our center. Of those, 7 patients (12.7%) had surgical LVR prior to LuTX and 14 (25.5%) had endoscopic LVR. Those patients were compared to the other 34 patients without previous intervention. Data is presented as LVRS (n=7) vs. ELVR (n=14) vs. controls (n=34). Results Despite a significantly different distribution in sex (female: 21.4% vs. 57.1% vs. 64.7%; p=0.023), no other differences were observed in all other recipient characteristics (age: 58 vs 56 vs. 56 years | BMI: 23.2 vs. 20.9 vs. 22.15 | TLCr: 9.6 vs. 7.9 vs. 7.8L | PAP: 33 vs. 30 vs. 30mmHg | waiting time: 271 (15-2350) vs. 747 (48-2161) vs. 1098 (6-3962) days). The lung allocation score (LAS) at time of LuTX did not show any clinically relevant differences between the three groups (32.5 vs. 32.2 vs. 32.9; p=0.028). 4 patients underwent bilateral LVRS, 3 unilateral LVRS. ELVR was performed with valves in 9 cases and with coils in 6 cases, evenly distributed in all lobes. Median duration from LVR to listing for LuTX was 303 (LVRS) and 508 (ELVR) days. Median duration from LVR to LuTX was 961 (397-3194) and 823 (8-2704) days respectively. After LuTX no significant differences were observed in ICU stay (7 vs. 10 vs. 11 days), hospitalization (48 vs. 41 vs. 51 days) and lung function (3-months post-LuTX FEV1: 80% vs. 78% vs. 79% | 3-months RV: 118% vs. 120% vs. 125%). No significant differences were observed in survival (1 and 3year survival: 100% vs. 100% vs. 85.3; p=0.07). Conclusion In our recent cohort of patients, LVRS and ELVR prior to lung transplantation did not impact short- and medium-term post-LuTX outcomes. Although the benefit and the precise indications of the different LVR methods remain to be elucidated in prospective trials, LVRS and ELVR can be safely considered for patients prior to lung transplantation.

Purpose Low cardiac output syndrome is associated with significant mortality. In patients with refractory low cardiac output left ventricular assist devices (VAD) are used to re-establish cardiac output and to prevent death. However, long-term LVAD implantation in these is complicated by a high rate of right heart failure and mortality. Therefore, our strategy is to implant a short-term VAD (left or biventricular) as a bridge to decission. Methods We retrospectively analysed data from 66 patients who received a short-term LVAD support prior to implantation of a long-term LVAD or HTx between 2003 and 2014. We performed short-term LVAD (CentriMag; Thoratec) implantation via median sternotomy with percutaneous cannulas. Patients were included regardless of perioperative status and severity of heart failure. Patients suffering postcardiotomy cardiogenic shock, receiving isolated RVAD as well as posttransplant patients were excluded from this study. Results Mean duration of support in the survivor group was 35 ± 25 days versus 25 ± 25 days in the nonsurvivor group (n.s.), range from 1 to 109 days. The overall survival on support was 40 (60%) patients. In the survivor group 12 patients could be successfully weaned from the system, 12 patients received a heart transplant and in 16 a long-term VAD was implanted. In the nonsurvivor group the rate of pre-operative extracorporeal life support, the rate of postoperative renal failure and multiorgan failure was significantly higher. Conclusions Thanks to its capacity for full ventricular support, short-term univentricular or biventricular LevotronixCentriMag VAD currently represents an ideal solution for bridge-to-decision.

OBJECTIVES Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. METHODS Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. RESULTS There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. CONCLUSIONS Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further larger prospective trials are warranted to confirm our preliminary results and to elaborate long-term outcomes.

Objectives We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. Background Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. Methods A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. Results Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p Conclusions Treatment of brain-dead donors with dopamine of 4 μg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115)

The aim of this study was to investigate the prognostic value of circulating troponin I (TNI)-autoantibodies in plasma of patients with chronic heart failure. Sera of 390 heart failure patients were tested for the presence of anti-TNI antibodies by enzyme-linked immunosorbent assay (ELISA), including 249 (63.8% of total) patients with dilated cardiomyopathy (DCM) and 141 (36.2% of total) patients with ischemic cardiomyopathy (ICM). A total of 72 patients (18.5% of total) were female and 318 (81.5% of total) were male. Mean patient age was 54.6 ± 11.3 years and mean follow-up time was 3.8 ± 3.2 years. TNI-autoantibodies (titer of ≥1:40) were detected in 73 out of 390 patients (18.7% of total). In TNI-autoantibody positive patients mean left ventricular ejection fraction (LVEF) was 27.6 ± 5.8%, compared to 25.8 ± 5.9% in TNI-autoantibody negative patients, P = 0.03. The combined end-point of death (n = 118, 30.3% of total) or heart transplantation (HTX) (n = 44, 11.3% of total) was reached in 162 patients (41.5% of total). Kaplan-Meier analysis demonstrated superior survival (combined end-point of death or HTX) in patients with DCM versus ICM (P = 0.0198) and TNI-autoantibody positive patients versus TNI-autoantibody negative patients (P = 0.0348). Further subgroup analysis revealed a favorable outcome in TNI-positive patients with heart failure if the patients suffered from DCM (P = 0.0334), whereas TNI-autoantibody status in patients with ICM was not associated with survival (P = 0.8486). In subsequent multivariate Weibull-analysis, a positive TNI serostatus was associated with a significantly lower all-cause mortality in DCM patients (P = 0.0492). The presence of TNI-autoantibodies in plasma is associated with an improved survival in patients with chronic DCM, but not ICM. This might possibly indicate a prophylactic effect of TNI-autoantibodies in this subgroup of patients, encouraging further studies into possible protective effects of antibodies against certain cardiac target structures.

Exhaust gas turbochargers are a major part of current strategies for reducing CO2 emissions — especially in the gasoline engine. To optimally support downsizing and downspeeding, turbochargers must react as fast as possible, and the exhaust gas volumetric flow to the turbine must be exactly adjustable with a wastegate. Electric motor actuation is advantageous here. However, it places specific requirements on the wastegate which Continental has taken into account in its new generation of turbochargers.

The prevalence, pathophysiology, and clinical indicators of valvular amyloid deposition have not been clarified yet.One hundred fifty surgically resected heart valve specimens [67.4+/-1.0 years; aortic stenosis (AS), n=100; aortic regurgitation, n=19; mitral stenosis, n=7; mitral regurgitation, n=24] were qualitatively, semiquantitatively, and immunohistochemically analyzed and correlated with clinical data.Amyloid was found in 83/150 specimens with highest prevalence in AS (74/100), intermediate prevalence in mitral stenosis (2/7) and regurgitation (7/24), and lowest prevalence in aortic regurgitation (2/19). Severe and polymorphic amyloid deposits were almost exclusively found in AS (35/100). Filamentous cloudy amyloid patterns occurred with the same frequency in AS (29/100). A combination of both was found only in AS (n=7/100). By immunohistochemistry, none of the most common amyloid proteins was identified except for a weak staining by the apolipoprotein AI antibody, but more intense adjacent to amyloid deposits. Amyloid correlated with valvular thickening (P.05), hyperlipidemia (P=.07), coronary artery disease (P=.084), and obesity (P=.082).Localized valvular amyloid is predominantly found in stenotic aortic valves. It appears to depend on atheroinflammatory conditions and high shear-stress hemodynamics. Further studies are needed to identify the underlying protein.

During cold storage of donor hearts, reactive oxygen species produced by intracellular redox-active chelatable iron potentially alter myocardial function. To reduce this cold-induced injury we investigated the efficacy of two new modifications of the well established histidine-tryptophan-ketogluterate (HTK) solution (Custodiol) with the addition of N-alpha-acetyl-l-histidine and iron-chelators in a heterotopic rat heart transplantation model. The donor hearts were cardioplegically arrested with 20 ml cardioplegia and stored for 1 h. Then the hearts were anastomosed to the abdominal aorta and vena cava of the recipient (n=30). After 1 h reperfusion, myocardial function and energy charge potential were measured in three groups: HTK-1: addition of l-arginine and N-alpha-acetyl-l-histidine; HTK-2: addition of iron-chelators deferoxamine and LK-614; traditional HTK - control. After 1 h reperfusion, left ventricular systolic pressure (106+/-33 vs. 60+/-39, vs. 67+/-8 mmHg, P

BACKGROUND Hyperlipidemia is an important complication after organ transplantation and may contribute to the development of posttransplant-accelerated coronary artery disease. Immunosuppressive therapy, especially mammalian target of rapamycin inhibitors, induces a considerable increase in cholesterol and triglyceride plasma levels. Omega-3 fatty acids (FAs) exert cardioprotective effects supporting a therapeutic role in cardiovascular conditions. METHODS An observational study of omega-3 FAs 4 g/day was performed in 15 heart transplant recipients with hypertriglyceridemia. Six patients received rapamycin, and nine received everolimus. Apart from one patient the immunosuppressive therapy was combined with mycophenolate mofetil, only one patient received steroids; two patients presented with diabetes. RESULTS Mean triglyceride levels before heart transplantation (HTx) were 137+/-54 mg/dL. After HTx, before sirolimus or everolimus treatment triglyceride level had increased to 188+/-67 mg/dL (P

We investigated tolerability and efficacy of ezetimibe treatment (10 mg/d) in 25 heart allograft recipients already on stable statin therapy. Total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), triglycerides (TG), immunosuppressant drug levels, laboratory and clinical parameters were assessed before, four months and one yr after initiation of ezetimibe treatment. Mean equivalent statin dose was 53.5 +/- 12.3 mg of pravastatin, remaining unchanged throughout the study period. Ezetimibe was generally well tolerated, only two patients (8%) discontinued ezetimibe due to stomach pain or headache. Mean TC decreased from 231.8 +/- 6.4 mg/dL before therapy to 202.2 +/- 8.8 mg/dL after four months and 192.9 +/- 7.0 mg/dL after one yr (p < 0.001). Mean LDL-C decreased from 143.1 +/- 5.4 mg/dL to 121.4 +/- 7.9 mg/dL (month 4; p < 0.05) and 107.1 +/- 5.6 mg/dL (one yr; p < 0.001). TG decreased from 182 +/- 14.3 mg/dL to 173.3 +/- 17.5 mg/dL after one yr (p < 0.05), whereas HDL-C was unchanged. Initial LDL-C and cardiac diagnosis before transplantation were identified as predictors of absolute LDL-C reduction. Immunosuppressant drug doses and blood concentrations were unchanged as well as other laboratory and clinical parameters. Ezetimibe appears safe and effective for further reduction of TC and LDL-C in heart allograft recipients already on stable statin therapy. Extent of pre-treatment LDL-C and cardiac disorder prior to transplantation appear to correlate with the efficacy of ezetimibe therapy.

Background To improve the rate of successful heart transplantations, organ preservation should be optimized in cardiac transplantation surgery. Iron-dependent oxidative damage and iron-independent, chloride-dependent injury of the endothelium have been described after cold ischemic storage and reperfusion, leading to an enhanced rate of complications and unfavorable outcomes. This screening study tested the effects of iron chelator supplementation in different histidine–tryptophan–ketoglutarate (HTK) organ preservation solutions on endothelial function in a long-term storage model of the isolated rat aorta. Methods Isolated rat aortic rings underwent a 24-hour cold ischemic preservation in different HTK solutions supplemented with iron chelators of low (deferoxamine) and high (LK-614) membrane permeability. In vascular reactivity measurements we investigated the phenyleprine-induced contraction and both endothelium-dependent and -independent vasorelaxation by using cumulative concentrations of acetylcholine and sodium nitroprusside with and without an additional external oxidant injury during re-oxygenation. Results Traditional HTK solution, Custodiol, failed to prevent endothelial dysfunction in our experiments. Use of chloride-poor HTK solutions containing N-α-acetyl- l -histidine with and without supplementation with LK-614, but not with deferoxamine, resulted in significant improvement of impaired endothelial function; moreover, complete protection of the endothelium was feasible after 24-hour cold storage. Endothelium-independent functions of vascular smooth muscle were not affected in any of the groups. Conclusions Our results demonstrate the important pathophysiologic role of iron-dependent oxidative injury in the development of endothelial dysfunction after cold storage, which can be prevented by cell-permeable iron chelators.

Objective: Ischemia and reperfusion during heart transplantation cause damage to cardiomyocytes and endothelial cells and may initiate later acute rejection. Free oxygen radicals generated by iNOS are widely accepted to be responsible for ischemic injury. Increased iNOS expression on cardiac tissue may represent a more intensive tissue injury during ischemia and reperfusion in heart transplantation. The aim of this study was, therefore, to test the hypothesis that increased iNOS expression in early postoperative endomyocardial biopsies correlates with rejection or infection episodes in the later postoperative course. Patients and methods: Right ventricular endomyocardial biopsies were obtained from heart transplantation recipients at transplantation and during the first 2 weeks postoperatively. The recipients were divided into three groups dependingonthepostoperative courseduringthefirstyearaftertransplantation:patientsingroup1hadan uncomplicatedpostoperativecourse, patients in group 2 developed significant signs of postoperative infection, while patients in group 3 presented with acute rejection (grade 2R ISHLT). The expression was analyzed in a semi-quantitative score. Results: iNOS expression was found in cardiomyocytes, endothelial cells, infiltrating cells, and vascular smooth muscle cells. At the time of heart transplantation, the expression was significantly increased in the rejection group compared to the other groups. This increase was even more pronounced in week 2. Conclusions:The present study shows that an increased iNOS expression at the time of heart transplantation could precede an acute rejection in the later postoperative course. Thus, measurements of iNOS expression may be of predictive value for an increased rejection risk and therefore offer the possibility of earlier therapeutic intervention. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Objective Zonal organ allocation system comprises organ procurement by teams within a specific geographical area of each retrieval team. Therefore, in a substantial number of cases organs are retrieved by 'foreign' teams and are sent for transplantation to the implanting centre. The aim of this study was to assess the impact of zonal organ allocation system on early- and long-term outcomes after lung transplantation (LTx). Methods Included were 331 consecutive patients who underwent LTx performed at Harefield Hospital between January 2007 and January 2015. Recipients were divided into two groups depending on the organ retrieval team: 204 (61.6%) patients were transplanted using lungs procured by our institutional team (institutional group), whereas 127 (38.4%) organs were retrieved by other teams (external group) from experienced transplant centres in the UK. To exclude selection bias and other confounders, a 1:1 propensity score-based matching procedure was performed resulting in a total number of 238 donors and recipients who were well matched for baseline characteristics. The primary end-points were overall survival after LTx and freedom from bronchiolitis obliterans syndrome (BOS). Secondary end-points were perioperative clinical characteristics as well as adverse events that occurred over the follow-up. Result After propensity score matching all donor characteristics and all baseline recipient characteristics were statistically similar between the two groups. In terms of early postoperative results, both groups were statistically comparable. However, there was a trend towards higher incidence of primary graft dysfunction in the external group (P = 0.054). Regarding long-term results with up to 7 years of follow-up, the overall survival also appeared to be poorer in the external group; however, this difference did not reach statistical significance. The freedom from BOS over the long-term follow was significantly poorer in the external group (P = 0.040). Conclusion Despite excellent early outcomes the zonal allocation system might be associated with significantly poorer long-term outcomes in terms of freedom from BOS after bilateral LTx. Further research is needed to find the underlying factors leading to these results.

OBJECTIVES The true impact of postoperative blood pressure (BP) control on development of aortic regurgitation (AR) following continuous-flow left ventricular assist device (CF-LVAD) implantation remains uncertain. This study examines the influence of BP in patients with de novo AR following CF-LVAD implantation. METHODS All patients with no or

Anemia after heart transplantation is common; however, there are scant data on etiology and treatment. This study evaluates type of anemia and the effects of erythropoietin therapy.In 37 anemic heart transplant recipients (31 male/59.1+/-10.3 years/hemoglobin12.0 g/dl), complete anemia work-up was performed including erythropoietin determination. For three months, 12 anemic patients with renal failure (9 male/64.1+/-13.6 years) were treated with 1-3x4000 IU of epoietin beta/week; treatment endpoints were hemoglobin levels and quality of life as determined by questionnaire.In 31 patients no other cause of anemia than renal insufficiency (mean creatinine 1.9+/-0.9 mg/dl, mean calculated GFR 50.8+/-21.5 ml/min, no hemodialysis) was found; in 93.5% of these patients with renal insufficiency, measured erythropoietin levels were markedly lower than predicted [Beguin Y, Clemons GK, Pootrakul P, Fillet G. Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin. Blood 1993; 81(4):1067-1076.]. There was an inverse correlation of hemoglobin levels with serum creatinine/creatinine clearance and a strong trend for inverse correlation of erythropoietin levels. All 12 patients treated with erythropoietin showed a significant increase in hemoglobin levels after three months returning to pre-treatment values within 3 months of cessation of therapy (before study 10.8+/-1.1 g/dl, end of study 14.1+/-1.7 g/dl, three months after end of study 11.6+/-2.1 g/dl; p0.005). Quality of life was significantly improved in eight patients (75%).Anemia after heart transplantation is associated with moderate renal failure and low erythropoietin levels in most patients. Erythropoietin therapy resulted in increased hemoglobin levels in all and improved quality of life in 75% of patients. Erythropoietin may be a superior marker of functional renal impairment after heart transplantation; its therapeutic substitution allows effective anemia management and improves quality of life.

Mycophenolate mofetil (NIMF) pharmacokinetics vary widely, and enterohepatic recirculation of the drug and its metabolites may be altered by concurrently administered immunosuppressants, including the widely used agent cyclosporin A (CsA). A reliable method of achieving effective and well-tolerated levels of NIMF-based immunosuppression would be of eminent interest.This study compared the use of measured mycophenolic acid (MPA) trough levels (C0) and abbreviated AUC estimation by limited-sampling strategies for monitoring MPA exposure in stable heart transplant recipients (1 year after transplantation) receiving a CsA-containing or CsA-free immunosuppressive regimen.The treatment groups were receiving chronic maintenance immunosuppressive regimens consisting of either CsA/MMF or rapamycin (RAPA)/MMF. An additional subgroup of patients was switched from the CsA-containing regimen to the RAPA-containing regimen. Fasting venous blood samples were obtained before dosing and at 40, 75, 120, and 240 minutes after administration of the morning dose of MME The validated Emit assay was used to measure MPA plasma concentrations. Dose adjustment of AUCs was performed by dividing the AUC by the morning NIMF dose in grams. Cmax after administration of the morning dose was determined from available MPA data points using curve-fitting analysis. The increase to Cmax (Cmax-C0) was calculated, and dose adjustment was performed as before. Abbreviated 12-hour MPA AUCs were estimated using a limited-sampling strategy (before dosing and 30 and 120 minutes after dosing) based on high-performance liquid chromatography data. Adverse events were monitored during routine follow-up visits.The study included 47 patients receiving CsA/MMF, 15 receiving RAPA/MMF, and 9 who were switched from CsA/MMF to RAPA/MME The population included 55 men and 7 women, with a mean age of 58.94 years and a mean weight of 81.85 kg. The only significant differences in baseline clinical characteristics between groups were the mean number of years since heart transplantation (3.62 CsA/MMF vs 8.53 RAPA/MMF; P0.01) and the proportions of patients still receiving corticosteroids (44.7% vs 13.3%, respectively; P0.01). Reported adverse events were generally mild, including leukopenia (8.1%), diarrhea (6.5%), and abdominal pain (4.8%), and did not require drug discontinuation. In patients receiving CsA/MMF, MPA AUCs ranged from 19.67 to 81.80 mg/h.L (mean [SD], 41.92 [14.14] mg/h.L). MPA Co levels were poorly correlated with total AUC (r2=0.36). MPA Co levels of 0.5 and 1.6 mg/L were correlated with AUCs of30 and40 mg/h.L, respectively. In patients receiving RAPA/MMF, MPA AUCs ranged from 34.40 to 87.60 mg/h.L (mean, 51.07 [15.80] mg/h.L). The correlation between Co and total AUC was better than in the CsA/MMF group (r2=0.61). MPA C0 levels of 1.0 and 2.3 mg/L were correlated with AUCs of 30 and 40 mg/h.L, respectively. Statistically significant differences between RAPA/MMF and CsA/MMF were noted in the mean MMF dosage (1.90 [0.71] vs 2.87 [0.78] g/d, respectively; P0.001), the mean dose-adjusted MPA AUC (60.95 [27.42] vs 31.92 [16.12] mg/h.L.g MMF; P0.001), and mean dose-adjusted MPA C0 levels (5.10 [3.41] vs 1.41 [0.95] mg/L.g; P0.001). The dose-adjusted increase to Cmax after morning dosing was comparable between groups, and there was no difference in the frequency distribution of Cmax. In the group switched from the CsA-containing regimen to the RAPA-containing regimen, the changes in MMF dose, dose-adjusted AUC, and MPA C0 levels were similar to those in the CsA/MMF and RAPA/MMF groups.In this comparison of measured MPA C0 levels and 12-hour MPA AUCs estimated by a limited-sampling strategy in stable heart transplant patients receiving chronic maintenance immunosuppressive therapy with CsA/MMF or RAPA/MMF, abbreviated AUC estimation predicted drug exposure more accurately than did measured C0 levels. Thus, MPA AUCs obtained by limited sampling may be useful in guiding clinical management and dosing. However, further study is required, including validation of these findings in clinical outcome studies.

Together with Renault Siemens VDO developed the first direct injection system (DI) in 1999 for a gasoline engine manufactured in Europe: the 2.0 l naturally aspirated engine of the Megane and Laguna. In 2001 the first European series production vehicles with lean-burn engines were to follow (Citroen C5 und Peugeot 406). Two years later the Mercedes-Benz C-Class was introduced with the first DI system for a turbocharged 1.8 l gasoline engine with stratified combustion. In the meantime Siemens VDO has continued to drive the development of piezo and solenoid actuated DI injectors for gasoline engines. This feature gives a summary of DI advantages and describes a new generation of solenoid injectors for homogeneous DI, capable of multistream spray.