Early experience with the Impella pump: Single-center registry.

BACKGROUND: With the rapid development of mechanical circulatory support technologies, patients presenting with cardiogenic shock have gained access to various treatment opportunities which were not until recently available. The Impella® pump (Abiomed, Danvers, USA) is a minimally invasive device which provides excellent left ventricular unloading and full circulatory support. The aim of the study was to review our center's experience with Impella® and to analyze the major adverse events associated with the device. METHODS: From January 2020 to January 2022, a total of 32 patients underwent Impella® implantation at our center for various indications. RESULTS: The mean age at surgery was 60.3 ± 12.4 years and 9.4% were female. All patients presented with acute cardiogenic shock in INTERMACS Class I (53.1%) and INTERMACS Class II (46.9%). Twenty-six patients (81.25%) out of the whole cohort have been mobilized on Impella® support. Seventeen patients (53.1%) have been weaned from the Impella® support and 10 patients (31.3%) have been bridged to durable LVAD. The median time on Impella® was 7 days (IQR 5.0-11.0). 30-day mortality was 37.5%, with 56.25% survival until hospital discharge. Only one patient developed vascular complications consisting of arm hypoperfusion. There were no cases of stroke on Impella® support. CONCLUSION: The Impella® axial-flow pump seems an appropriate therapeutic option for patients with acute cardiogenic shock requiring partial or full hemodynamic support. It also provides sufficient left ventricular unloading to allow full mobilization and neurological assessment of the patients. Furthermore, Impella® offers a high rate of myocardial recovery.

Impact of severe mitral regurgitation on postoperative outcome after durable left-ventricular assist device implantation.

BACKGROUND: Mitral valve regurgitation (MR) is a common finding in patients with end-stage heart failure. The aim of the study was to analyze the impact of preoperative moderate-to-severe MR on postoperative outcomes and survival after durable left-ventricular assist device (LVAD) implantation. METHODS: From August 2010 to May 2021, 246 patients underwent a durable LVAD implantation. We stratified the patients into two groups: Group A (n = 109) presented with MR 0-I°, and Group B presented with MR II-III° (n = 137). MR II-III° was defined according to the current recommendations (i.e., vena contracta ≥ 7 mm, regurgitation volume ≥ 30 ml or effective regurgitation orifice area ≥ 20 mm2 ). RESULTS: Significantly more patients in Group B suffered from pulmonary hypertension and presented with chronic obstructive lung disease. We observed significantly higher rates of tricuspid regurgitation (TR) II-III° in Group B (76.1%) versus Group A (14.8%) (p < 0.001) and TR III° in Group B (30.4%) versus Group A (3.7%) (p < 0.001). There was no difference in the incidence of right heart failure between the groups. Within our cohort, the in-hospital, 1-year, 3-year, and 5-year mortality was 22.4%, 32.1%, 50.7%, and 64.4%, respectively. Group B showed significantly worse overall survival (p = 0.05). Patients with preoperative TR II-III° had a significantly worse survival than those with TR 0-I° (p = 0.048). In patients presenting with MR II-III°, we discovered that TR III° seems to predict both in-hospital and mid-term mortality. CONCLUSION: MR II-III° negatively affects the outcomes in patients requiring LVAD implantation. Persisting MR II-III° is an independent predictor of mortality. Patients with concomitant preoperative TR II-III° are at increased risk of developing postoperative major adverse events. Addressing the MR might be considered for these patients.

Initial experience with CytoSorb therapy in patients receiving left ventricular assist devices.

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.

Outcomes of left ventricular assist device implantation for advanced heart failure in critically ill patients (INTERMACS 1 and 2): A retrospective study.

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.

Prediction of acute kidney injury after left ventricular assist device implantation: Evaluation of clinical risk scores.

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.

The Impact of Obesity on Left Ventricular Assist Device Outcomes.

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 > 30 kg/m2) on post-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 ≥ 30 kg/m2 representing the obesity threshold. The first group (n = 162) had an average BMI of 24.2 kg/m2 (±2.9), and the second group (n = 48) had an average BMI of 33.9 kg/m2 (±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 ± 1.6, group 1; 2.6 years ± 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 > 0.05). Postoperative complications were unvaried between the obese and the non-obese group (all with p > 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.

Effect of donor cardiac arrest and arrest duration on outcomes of lung transplantation.

BACKGROUND: Limited data are available about lung transplantation (LTx) from donors suffering cardiac arrest (CA) prior to actual donation. METHODS: 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 ("CA < 20"), and CA downtime equal to or more than 20 min ("CA > 20"). Early and mid-term outcomes after LTx were compared among the three groups. RESULTS: A total of 237 LTx were performed during the study period. One hundred eighty-eight patients received organs from "NoCA" donors, 25 from "CA < 20" donors, and 24 patients from "CA > 20" donors. There was a trend toward better overall cumulative survival in both CA groups (log rank p = 0.076) whereas the survival in the "CA > 20" 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. CONCLUSIONS: 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.

Lung transplantation in chronic obstructive pulmonary disease: long-term survival, freedom from bronchiolitis obliterans syndrome, and factors influencing outcome.

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.

Treatment of Staphylococcus aureus infection with sphingosine in ex vivo perfused and ventilated lungs.

BACKGROUND: Ex vivo lung perfusion (EVLP) has expanded the donor pool for lung transplantation. Pulmonary Staphylococcus aureus infection, especially that caused by multidrug-resistant strains, is a severe threat to posttransplantation outcomes. Sphingosine is a lipid compound that exhibits broad-spectrum antibacterial activity. Therefore, we aimed to evaluate the effects of S aureus infection on EVLP and whether sphingosine administration during EVLP prevents infection with S aureus. METHODS: Eighteen pigs were randomly assigned to 3 groups: uninfected, infected with S aureus with NaCl treatment, or infected with sphingosine treatment. Bacterial numbers were determined before and after treatment. Sphingosine concentrations in the lung tissues were determined using biochemical assays. Lung histology, lung physiological parameters, perfusate content, lung weight, and cell death were measured to analyze the effects of infection and sphingosine administration on EVLP. RESULTS: Sphingosine administration significantly reduced the bacterial load. The concentration of sphingosine in the bronchial epithelium was elevated after sphingosine administration. S aureus infection increased pulmonary artery pressure and pulmonary vascular resistance. Lung edema, histology scores, lactate and lactate dehydrogenase levels in the perfusate, ΔPO2 in the perfusate, static lung compliance, and lung peak airway pressure did not differ among the groups. CONCLUSIONS: Infection of S aureus did not affect the lung function during EVLP but induced higher pulmonary artery pressure and pulmonary vascular resistance. Administration of sphingosine effectively eliminated S aureus without side effects in isolated, perfused, and ventilated pig lungs.

Incidence of malignancies after lung transplantation and their effect on the outcome. 26 years' experience.

Background: Malignancy is a significant, life-limiting complication after lung transplantation (LuTx) and the second common long-term cause of death. We aimed to investigate its incidence and effect on the outcome. Methods: This is a retrospective observational study. Between 1996 and 2022, n = 627 lung transplantations (LuTx) were performed in our department. We used our institutional database to identify recipients with malignancies after LuTx and examined the malignancies' incidence and mortality. Results: N = 59 malignancies occurred in n = 55 (8.8%) LuTx recipients. The post-LTx malignancies incidence was 9.4% (59/627). We report the following rates based on their location: n = 17/55 (28,8% of all recipients diagnosed with malignancies) skin, n = 10/55 (16,95%) gastrointestinal, n = 9/55 (15,3%) respiratory, n = 5/55 (8,48%) lymphatic, n = 13/55 (23,6%) other, n = 5 (8,48%) multiple synchronous.During this study period, a total of n = 328 deaths after LuTx was determined. N = 29 (8,84% of all deaths) were malignancy induced, corresponding to a total malignancy-induced mortality of 4.6% (n = 29/627). The majority of deaths were attributed to GI adenocarcinoma and PTLD. Malignancies' origin, primary COPD diagnosis, type, and specific age group were significantly survival-related (p-values <0.05). The most affected organ was skin and showed the best prognosis. PTLD had the fastest and pancreatic the latest onset. Conclusions: This is the first report of its kind in a large cohort of german LuTx recipients. The prevalence ranking of the three commonest malignancy were skin > colorectal > PTLD. Post-LTx malignancy was the second commonest cause of death. Further studies are needed, while post-LuTx malignomas remain a serious impairment of long-term LuTx survival.

Vascular complications after peripheral veno-arterial extracorporeal life support cannulation in cardiogenic shock.

Background: Extra Corporeal Life Support (ECLS) is an evolving therapy in therapy-resistant cardiogenic shock (CS). Vascular cannulation in emergency situations can be accomplished through puncture of the femoral vessels by specialised teams. Since lower limb ischemia constitutes one of the major complications following cannulation, a distal perfusion cannula (DPC) has emerged as standard of care. We here aimed to analyse the impact of the DPC on limb perfusion and 6-month survival rate. Methods: In a retrospective study from January 2012 to December 2018, 98 patients with cardiogenic shock and peripheral (v-a) ECLS implantation with documented limb perfusion status were identified and analysed. Demographic data, laboratory parameters, cause of CS, comorbidities, limb perfusion complications and complication management were analysed. Results: 53 patients (54%) received ECLS therapy in referral centers by our mobile ECLS team, while in 45 patients (46%) the cannulation occured in our center. 71 patients (72%) received a DPC (group A) at the time of ECLS implantation, whereas 27 (28%) (group B) did not or received later (14 patients owing to limb ischemia). 44 patients (45%) developed limb ischemia as a complication of ECLS therapy (31% in group A and 81% in group B- p < 0.001). The 6-month survival rate was 28% in our study cohort (30% in group A and 22% in group B- p = 0.469). Conclusion: Lower limb ischemia remains a serious complication after peripheral ECLS cannulation in CS, especially when a DPC is absent. Standardised DPC implementation may reduce the rate of severe limb complications in peripheral ECLS.

Introduction of machine perfusion of donor hearts in a single center in Germany.

Introduction: Organ shortage, subsequent use of extended donor criteria organs and high-risk recipients needing redo-surgery are increasing the complexity of heart transplantation. Donor organ machine perfusion (MP) is an emerging technology allowing reduction of ischemia time as well as standardized evaluation of the organ. The aim of this study was to review the introduction of MP and analyze the results of heart transplantation after MP in our center. Methods: In a retrospective single-center study, data from a prospectively collected database were analysed. From July 2018 to August 2021, fourteen hearts were retrieved and perfused using the Organ Care System (OCS), 12 hearts were transplanted. Criteria to use the OCS were based on donor/recipient characteristics. Primary objective was 30-day survival, secondary objectives were major cardiac adverse events, graft function, rejection episodes as well as overall survival in the follow-up and assessment of MP technical reliability. Results: All patients survived the procedure and the postoperative 30-day interval. No MP related complications were noted. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsy showed excellent results with no or mild rejection. Two donor hearts were rejected after OCS perfusion and evaluation. 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 increased the number of acceptable donor hearts. Additional clinical trials are necessary to develop guidelines regarding the application of MP.

Composition of ex vivo perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation.

Background: Ex vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities. Methods: Following cardiac arrest, the lungs were harvested and were categorized into two groups: immediate (I-EVLP) and delayed EVLP (D-EVLP), after 1 and 9 h of CSP, respectively. The D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing only dextran (CD) or dextran and albumin (CDA). The cytokine/chemokine levels were analyzed at baseline (0 h) and after 1 and 4 h of EVLP using Luminex-based multiplex assays. Results: Within 4 h of EVLP, the concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α, and IL-1ß increased significantly (P < 0.05) in all experimental groups. The CD solution contained lower concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-2, IL-12, IL-10, IL-4, IL-1RA, and IL-18 (P < 0.05) compared with those of the Steen solution. The concentration levels of all experimental groups have correlated negatively with the oxygenation capacity values (P < 0.05). Protein concentration levels did not reach statistical significance for I-EVLP vs. D-EVLP and CD vs. CDA solutions. Conclusion: In a porcine cardiac arrest model, a longer period of CSP prior to EVLP did not result in an enhanced protein secretion into perfusates. The CD solution reduced the cytokine/chemokine secretion most probably by iron chelators and/or by the protecting effects of dextran. Supplementing with albumin did not further reduce the cytokine/chemokine secretion into perfusates. These findings may help in optimizing the preservation procedure of the lungs, thereby increasing the donor pool of organs.

Immunosuppression with tacrolimus early after orthotopic heart transplantation: a comparison of prograf and advagraf.

BACKGROUND: We compared trough levels and clinical outcomes in patients who received Prograf or Advagraf (tacrolimus) de novo following heart transplantation surgery. METHODS: Eighty-two patients were included in this follow-up study. Biopsy results were controlled for the first 3 months after orthotopic heart transplantation. Trough levels were monitored for 4 weeks: daily during the first 7 days and once every week thereafter. The lengths of stay in the hospital and in intensive care were compared. The end point of the study was the 1-year mortality rate. RESULTS: We found significant differences between the groups for both biopsy results and trough levels. Trough levels differed for the first 5 days and then converged on the sixth day. The levels remained comparable throughout the monitoring period. The 1-year mortality rates for Prograf and Advagraf were 20% and 15%, respectively. CONCLUSIONS: Trough levels were comparable after an adjustment period. There were no differences between the 2 groups in their 1-year mortality rates. These results suggest that Advagraf is a safe alternative to Prograf for patients who have undergone heart transplantation.

Lung Transplantation for Adult Respiratory Distress Syndrome after SARS-CoV-2 Infection.

Background The majority of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection present mild symptoms. However, some patients develop severe acute respiratory distress syndrome (ARDS) and subsequent irreversible lung damage despite extracorporeal membrane oxygenation, leaving lung transplantation the ultimate therapeutically option. Case Description Here, we report a case of lung transplantation in a 31-year-old male recipient suffering from post-coronavirus disease 2019 respiratory failure with irreversible ARDS after prolonged extracorporeal membrane oxygenation therapy. Conclusion Patient selection criteria are elucidated. One relevant mechanism for susceptibility to SARS-CoV-2 in the respiratory system, the acid sphingomyelinase/ceramide system might be altered during infection with SARS-CoV-2.

Custodiol-MP for ex vivo lung perfusion - A comparison in a porcine model of donation after circulatory determination of death.

INTRODUCTION: Ex vivo lung perfusion (EVLP) is an established technique to evaluate and eventually recondition lungs prior to transplantation. Custodiol-MP (C-MP) solution is a new solution, designed for clinical machine perfusion, that has been used for kidneys. The aim of this study was to compare the effects of EVLP with Custodiol-MP on lung functional outcomes to the gold standard of EVLP with Steen Solution™. MATERIAL AND METHODS: In a porcine EVLP model of DCDD (Donation after Circulatory Determination of Death), lungs were perfused with Steen Solution™ (SS, n = 7) or Custodiol-MP solution supplemented with 55 g/l albumin (C-MP, n = 8). Lungs were stored cold for 4 h in low potassium dextran solution and subsequently perfused ex vivo for 4 h. During EVLP pulmonary gas exchange, activities of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) as well as levels of lactate in the perfusate were recorded hourly. RESULTS: Oxygenation capacity differed significantly between groups (averaged over 4 h: SS 274 ± 178 mmHg; C-MP 284 ± 151 mmHg p = 0.025). Lactate dehydrogenase activities and lactate concentrations were significantly lower in Custodiol-MP perfused lungs.In a porcine model of DCDD with 4 h of EVLP the use of modified Custodiol-MP as perfusion solution was feasible. The use of C-MP showed at least comparable lung functional outcomes to the use of Steen SolutionTM. Furthermore C-MP perfusion resulted in significantly lower lactate dehydrogenase activity and lactate levels in the perfusate and higher oxygenation capacity.

Antimicrobial effects of inhaled sphingosine against Pseudomonas aeruginosa in isolated ventilated and perfused pig lungs.

BACKGROUND: Ex-vivo lung perfusion (EVLP) is a save way to verify performance of donor lungs prior to implantation. A major problem of lung transplantation is a donor-to-recipient-transmission of bacterial cultures. Thus, a broadspectrum anti-infective treatment with sphingosine in EVLP might be a novel way to prevent such infections. Sphingosine inhalation might provide a reliable anti-infective treatment option in EVLP. Here, antimicrobial potency of inhalative sphingosine in an infection EVLP model was tested. METHODS: A 3-hour EVLP run using pig lungs was performed. Bacterial infection was initiated 1-hour before sphingosine inhalation. Biopsies were obtained 60 and 120 min after infection with Pseudomonas aeruginosa. Aliquots of broncho-alveolar lavage (BAL) before and after inhalation of sphingosine were plated and counted, tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Immunostainings were performed. RESULTS: Sphingosine inhalation in the setting of EVLP rapidly resulted in a 6-fold decrease of P. aeruginosa CFU in the lung (p = 0.016). We did not observe any negative side effects of sphingosine. CONCLUSION: Inhalation of sphingosine induced a significant decrease of Pseudomonas aeruginosa at the epithelial layer of tracheal and bronchial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated pig lungs.

Rescue extracorporeal life support as a bridge to durable left ventricular assist device.

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.

Impact of troponin I-autoantibodies in chronic dilated and ischemic cardiomyopathy.

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.

Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs.

Ex-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46-89%) which leads to a donor-to-recipient transmission and after a higher risk of lung infection with reduced posttransplant outcome. We have previously shown that sphingosine very efficiently kills a variety of pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and epidermidis, Escherichia coli or Haemophilus influenzae. Thus, sphingosine could be a new treatment option with broadspectrum antiinfective potential, which may improve outcome after lung transplantation when administered prior to lung re-implantation. Here, we tested whether sphingosine has any adverse effects in the respiratory tract when applied into isolated ventilated and perfused lungs. A 4-h EVLP run using minipig lungs was performed. Functional parameters as well as perfusate measurements where obtained. Biopsies were obtained 30 min and 150 min after inhalation of sphingosine. Tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Hemalaun, TUNEL as well as stainings with Cy3-coupled anti-sphingosine or anti-ceramide antibodies were implemented. We demonstrate that tube-inhalation of sphingosine into ex-vivo perfused and ventilated minipig lungs results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea without morphological side effects up to very high doses of sphingosine. Sphingosine also did not affect functional lung performance. In summary, the inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated minipig lungs.