Pericardial Closure With Expanded Polytetrafluoroethylene Patch in Left Ventricular Assist Device Surgery.

To reduce adhesions after left ventricular assist device (LVAD) implantation, pericardial closure using an expanded polytetrafluoroethylene (ePTFE) patch has been suggested. However, as foreign material, ePTFE patches could increase the risk of infectious complications. In this single-center retrospective study, we investigated outcomes of pericardial closure using an ePTFE patch in LVAD implantation. We included all patients who underwent LVAD implantation at our center between 2011 and 2020 (n = 166). Primary endpoint was development of mediastinitis at any point of time between LVAD implantation and heart transplantation (HTx) or death. Secondary endpoint was overall survival. Preoperative and postoperative clinical data were collected to ensure comparability between the groups. We included 166 patients with LVAD. A total of 116 patients (70%) underwent pericardial closure using an ePTFE patch. There were significant differences between the groups in treatment setting, previous cardiac surgery, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level, development of driveline infection, and HTx. Patients with an ePTFE patch developed mediastinitis more frequently (16%) than patients without ePTFE patch (4%) ( p = 0.039). A significant difference in overall survival between the groups could not be confirmed ( p = 0.29). The use of PTFE patches for pericardial closure in LVAD implantation was associated with a higher incidence of mediastinitis, but not with a difference in overall survival.

Temporary circulatory support with surgically implanted microaxial pumps in postcardiotomy cardiogenic shock following coronary artery bypass surgery.

Objectives: Patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) surgery may develop postcardiotomy cardiogenic shock. In these cases, implantation of an Impella 5.0 or 5.5 microaxial pump offers full hemodynamic support while simultaneously unloading of the left ventricle. Methods: Preoperative, perioperative, and postoperative data of all patients receiving postoperative support with an Impella 5.0 or 5.5 after CABG surgery between September 2017 and October 2022 were retrospectively collected. Cohort built-up was performed according to the timing of Impella implantation, either simultaneous during CABG surgery or delayed. Results: A total of n = 42 patients received postoperative Impella support, of whom 27 patients underwent simultaneous Impella implantation during CABG surgery and 15 patients underwent delayed Impella therapy. Preoperative left ventricular ejection fraction was similarly low in both groups (26.7 ± 0.7% vs 24.8 ± 11.3%; P = .32). In the delayed cohort, Impella implantation was performed after a median of 1 (1; 2) days after CABG surgery. Survival after 30 days (75.6% vs 47.6%, P = .04) and 1 year (69.4% vs 29.8%, P = .03) was better in the cohort receiving simultaneous Impella implantation. Conclusions: The combined advantages of hemodynamic support and LV unloading with microaxial pumps may lead to a favorable survival in patients with left ventricular failure following CABG surgery. Early implantation during the initial surgery shows a trend toward a more favorable survival as compared with patients receiving delayed support.

Short-term mechanical support with the Impella 5.x for mitral valve surgery in advanced heart failure-protected cardiac surgery.

Introduction: Surgical treatment of patients with mitral valve regurgitation and advanced heart failure remains challenging. In order to avoid peri-operative low cardiac output, Impella 5.0 or 5.5 (5.x), implanted electively in a one-stage procedure, may serve as a peri-operative short-term mechanical circulatory support system (st-MCS) in patients undergoing mitral valve surgery. Methods: Between July 2017 and April 2022, 11 consecutive patients underwent high-risk mitral valve surgery for mitral regurgitation supported with an Impella 5.x system (Abiomed, Inc. Danvers, MA). All patients were discussed in the heart team and were either not eligible for transcatheter edge-to-edge repair (TEER) or surgery was considered favorable. In all cases, the indication for Impella 5.x implantation was made during the preoperative planning phase. Results: The mean age at the time of surgery was 61.6 ± 7.7 years. All patients presented with mitral regurgitation due to either ischemic (n = 5) or dilatative (n = 6) cardiomyopathy with a mean ejection fraction of 21 ± 4% (EuroScore II 6.1 ± 2.5). Uneventful mitral valve repair (n = 8) or replacement (n = 3) was performed via median sternotomy (n = 8) or right lateral mini thoracotomy (n = 3). In six patients, concomitant procedures, either tricuspid valve repair, aortic valve replacement or CABG were necessary. The mean duration on Impella support was 8 ± 5 days. All, but one patient, were successfully weaned from st-MCS, with no Impella-related complications. 30-day survival was 90.9%. Conclusion: Protected cardiac surgery with st-MCS using the Impella 5.x is safe and feasible when applied in high-risk mitral valve surgery without st-MCS-related complications, resulting in excellent outcomes. This strategy might offer an alternative and comprehensive approach for the treatment of patients with mitral regurgitation in advanced heart failure, deemed ineligible for TEER or with need of concomitant surgery.

Impact of total ischaemic time and disease severity class on graft function after bilateral lung transplantation.

OBJECTIVES: Total ischaemic time (IT) is considered a limiting factor in lung transplantation. In this retrospective study, we investigate effects of IT and disease burden on outcomes after bilateral lung transplantation. METHODS: A total of 1298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (follow-up 100%, median 54 months) were included. Pre-transplant diseases' severity (recipient body mass index, recipient age, previous lung transplantation, Tacrolimus immunosuppression, preoperative recipient extracorporeal membrane oxygenation support, lung volume reduction) for graft failure was individually calculated and-as IT-categorized. Vice versa adjusted Cox models were calculated. Considering competing risks, we assessed cumulative incidences of airway obstructive complications and chronic lung allograft dysfunction with death as competing risk factors for primary graft dysfunction were assessed by binary logistic regression. RESULTS: Higher disease burden significantly accelerated chronic lung allograft dysfunction and death occurrence (P < 0.001); IT did not. IT-adjusted disease burden strata showed 50% graft survival differences at 11 years after transplantation (range 24-74%), disease burden-adjusted IT strata 18% for all and 6% (54-60%) among those above 7 h. All significant primary graft dysfunction risk factors were diagnoses related, IT was not significantly important and odds ratios did not increase with IT. CONCLUSIONS: The eventual graft survival disadvantage that results from an IT between 7 and at least 11 h is negligible in contrast to frequent recipients' disease-based risk levels.

Does donor-recipient age mismatch have an influence on outcome after lung transplantation? A single-centre experience.

OBJECTIVES: Lack of organ donors demands transplantation of older lung allografts for recipients between 0 and 50 years. So far, it has not yet been investigated whether donor-recipient age mismatch affects long-term outcome. METHODS: Records of patients aged between 0 and 50 years were retrospectively reviewed. Donor-recipient age mismatch was calculated subtracting recipient age from donor age. Multivariable Cox regression analyses was performed to assess donor-recipient age mismatch regarding the end points' overall patient mortality, mortality conditioned to hospital discharge, biopsy-confirmed rejection and chronic lung allograft dysfunction. Furthermore, we performed competing risk analysis to analyse if age mismatch affects biopsy-confirmed rejection and CLAD while death being a competing risk. RESULTS: Between January 2010 and September 2021, out of 1363 patients who underwent lung transplantation at our institution, 409 patients fulfilled the eligibility criteria and were included. Age mismatch ranged between 0 and 56 years. Multivariable analysis revealed that donor-recipient age mismatch does not affect overall patient mortality (P = 0.19), biopsy-confirmed rejection (P = 0.68) and chronic lung allograft dysfunction (P = 0.42). There was no difference seen in CLAD (P = 0.166) and biopsy-confirmed rejection (P = 0.944) with the competing risk death (P = 0.765 and P = 0.851; respectively). CONCLUSIONS: Age mismatch between recipients and donors of lung allografts does not affect long-term outcomes after lung transplantation.

Lung transplant and severe coronary artery disease: results from a single-centre experience.

OBJECTIVES: The management of severe coronary artery disease at the time of a lung transplant remains a challenge. We analysed the short- and long-term outcomes of lung transplant recipients with severe coronary artery disease. METHODS: Records of adult patients who received transplants at our institution between April 2010 and February 2021 were reviewed retrospectively. Severe coronary artery disease was defined as coronary stenosis ≥70% (main stem ≥50%) seen on the coronary angiographic scans performed before or at the time of listing. Patient characteristics, perioperative and long-term outcomes were compared between patients with and without severe coronary artery disease. RESULTS: Among 896 patients who received lung transplants who had undergone coronary angiography before the transplant, 77 (8.5%) had severe coronary artery disease; the remaining 819 (91.5%) did not. Patients with severe coronary artery disease were older (p < 0.0001), more often male (p < 0.0001) and received transplants more often for pulmonary fibrosis (p = 0.0007). The median (interquartile range) follow-up was 46 (20-76) months. At the Cox multivariable analysis, severe coronary artery disease was not associated with death. Patients with pretransplant percutaneous transluminal coronary angioplasty and patients with coronary artery bypass graft surgery concomitant to a transplant had survival equivalent to that of patients without severe coronary artery disease (p = 0.513; p = 0.556). CONCLUSIONS: Severe coronary artery disease was not associated with decreased survival after a lung transplant. Concomitant coronary artery bypass graft surgery and pretransplant percutaneous transluminal coronary angioplasty can be used for revascularization.

Long-term paracorporeal pulsatile mechanical circulatory support in adolescent and adult patients.

OBJECTIVES: Our goal was to analyse adverse events in adolescent and adult patients with the Berlin Heart EXCOR and to assess the outcome of a subsequent heart transplant (HTX). METHODS: From 2006 to 2020, a total of 58 patients (12-64 years old) received a biventricular assist device (BIVAD) at our institution and were included in this study. RESULTS: The causes of biventricular heart failure were nonischaemic cardiomyopathy (62.1%), ischaemic cardiomyopathy (22.4%) and myocarditis (15.5%). The median INTERMACS score was I (I-III). The median age was 49 years (interquartile range, 34-55 years), and 82.8% were male. Causes of death were multiorgan failure (25.0%), septic shock (17.9%), cerebral haemorrhage (14.3%), bleeding (14.3%) and embolic events (14.3%). Major bleeding was more frequent in the patients who died while on BIVADs (60.7 vs 6.7%, P < 0.001). Wound infections were more prevalent in HTX recipients (n = 21, 70.0%). After BIVAD thrombosis, 104 chamber exchanges were performed in 28 patients (48.3%). HTXs were performed in 52.6% of the patients after a BIVAD support time of 316 ± 240 days. The mean time to follow-up of 30 HTX recipients was 1722 ± 1368 days. One-, 6- and 12-month survival after an HTX were 96.7%, 90.0% and 76.7%, respectively. Long-term survival after 5 and 10 years was 69.7%. CONCLUSIONS: Pump thrombosis, infections and bleeding after receiving a BIVAD did not preclude a successful HTX. Although only 50% of patients with BIVADs were successfully given a transplant, long-term survival after an HTX in patients with BIVAD was noninferior compared to that of other recipients.

Lung Retransplantation.

Lung retransplantation remains the standard treatment of irreversible lung allograft failure. The most common indications for lung retransplantation are acute graft failure, chronic lung allograft dysfunction, and postoperative airway complications. Careful patient selection with regards to indications, anatomy, extrapulmonary organ dysfunction (specifically renal dysfunction), and immunologic consideration are of utmost importance. The conduct of the lung retransplantation operation is arduous with special considerations given to operative approach, type of surgery (single vs bilateral), use of extracorporeal circulatory support, and hematological management. Outcomes have improved significantly for most patients, nearing short and midterm outcomes of primary lung recipients in select cases.

Heart transplantation across preformed donor-specific antibody barriers using a perioperative desensitization protocol.

Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen. A retrospective analysis was performed comparing heart transplant recipients with preformed donor-specific HLA-antibodies to recipients without donor-specific antibodies. Recipients with a positive virtual crossmatch received a perioperative desensitization protocol including tocilizumab intraoperatively, plasma exchange and rituximab followed by a six-month course of IgGAM. Among the 117 heart-transplanted patients, 19 (16%) patients underwent perioperative desensitization, and the remaining 98 (84%) patients did not. Cold ischemic time, posttransplant extracorporeal life support for primary graft dysfunction, and intensive care unit stay time did not differ between groups. At 1-year follow-up, freedom from pulsed steroid therapy for presumed rejection and biopsy-confirmed acute cellular or humoral rejection did not differ between groups. One-year survival amounted to 94.7% in the treated patients and 81.4% in the control group. Therefore, heart transplantation in sensitized recipients undergoing a perioperative desensitization appears safe with comparable postoperative outcomes as patients with a negative crossmatch.

Donor NK and T Cells in the Periphery of Lung Transplant Recipients Contain High Frequencies of Killer Cell Immunoglobulin-Like Receptor-Positive Subsets.

Introduction: For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs. recipient NK cells. Methods: Peripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry. Results: Within the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p<0.01) 3wk post DLTx compared to recipient NK cells. This effect was also observed in donor KIR+ T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (p<0.05) and KIR3DL/S1 (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected compared to recipient cells via CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells. Conclusion: Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx.

Risk Factors, Treatment and Prognosis of Patients with Lung Cancer after Heart Transplantation.

Long-term survival after heart transplantation (HTX) is impacted by adverse effects of immunosuppressive pharmacotherapy, and post-transplant lung cancer is a common occurrence. This study aimed to examine the risk factors, treatment, and prognosis of patients with post-transplant lung cancer. We included 625 adult patients who received HTX at Heidelberg Heart Center between 1989 and 2018. Patients were stratified by diagnosis and staging of lung cancer after HTX. Analysis comprised donor and recipient characteristics, medications including immunosuppressive drugs, and survival after diagnosis of lung cancer. A total of 41 patients (6.6%) were diagnosed with lung cancer after HTX, 13 patients received curative care and 28 patients had palliative care. Mean time from HTX until diagnosis of lung cancer was 8.6 ± 4.0 years and 1.8 ± 2.7 years from diagnosis of lung cancer until last follow-up. Twenty-four patients (58.5%) were switched to an mTOR-inhibitor after diagnosis of lung cancer. Multivariate analysis showed recipient age (HR: 1.05; CI: 1.01-1.10; p = 0.02), COPD (HR: 3.72; CI: 1.88-7.37; p < 0.01), and history of smoking (HR: 20.39; CI: 2.73-152.13; p < 0.01) as risk factors for post-transplant lung cancer. Patients in stages I and II had a significantly better 1-year (100.0% versus 3.6%), 2-year (69.2% versus 0.0%), and 5-year survival (53.8% versus 0.0%) than patients in stages III and IV (p < 0.01). Given the poor prognosis of late-stage post-transplant lung cancer, routine reassessment of current smoking status, providing smoking cessation support, and intensified lung cancer screening in high-risk HTX recipients are advisable.

Lung transplantation for pediatric pulmonary arterial hypertension-quo vadis?

In children with pulmonary arterial hypertension, lung transplantation illustrates a feasible treatment option once pharmacological therapy is exhausted. Timing of listing for lung transplantation in children remains difficult since hemodynamic deterioration often occurs abruptly and the time on the waiting list is usually hard to predict. Clear contraindications for lung transplantation are recent history of malignancies as well as irreversible end-organ failure. Generally, patients with pulmonary arterial hypertension in the absence of structural cardiac defects can safely undergo bilateral lung transplantation, combined heart-lung transplantation remains a procedure with a higher perioperative risk and should only be performed in selected cases with irreversible structural defects. Donor selection in recent years shows donors with extended criteria as well as lobar transplantation with good outcome, having the positive effect of broadening of the donor pool. Bridging to lung transplantation with veno-arterial ECMO treatment is feasible and has a good outcome in experienced transplant centers. Surgical considerations should include the risk of hemodynamic decompensation upon anesthesia induction and the need for extracorporeal support pre-, intra- and postoperative. Lung transplantation should be performed on veno-arterial ECMO support with either peripheral (>20 kg) or central cannulation (<20 kg). The surgical transplantation procedure includes the bronchial anastomosis as well as anastomoses of the pulmonary artery and the left atrium. Postoperative prolonged veno-arterial ECMO treatment for the immediate postoperative period allows for left ventricular remodeling given the new hemodynamic circumstances with lower pulmonary vascular resistance. Standard triple immunosuppression in most lung transplant programs currently includes steroids, mycophenolate mofetil and tacrolimus. Survival after pediatric lung transplantation for IPAH is comparable to pediatric lung transplants for other underlying diseases with a 1-year survival of approx. 80% and a 5-year survival of 64-65%. Therefore, evolving techniques in the field of lung transplantation led to overall improved survival prospects in children with end-stage pulmonary vascular disease.

A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

BACKGROUND: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts. METHODS: Five cynomolgus macaques underwent left orthotopic lung transplantation. Initial immunosuppression included equine ATG and anti-IL6RmAb induction, followed by triple-drug immunosuppression for 4 mo. Post-transplant, a nonmyeloablative conditioning regimen was applied, including total body and thymic irradiation. Rabbit ATG, belatacept, anti-IL6RmAb, and donor bone marrow transplantation (DBMT) were given, in addition to a 28-d course of cyclosporine. All immunosuppressant drugs were stopped on day 29 after DBMT. RESULTS: One monkey rejected its lung before DBMT due to AMR, after developing donor-specific antibodies. Two monkeys developed fatal post-transplant lymphoproliferative disorder, and both monkeys had signs of cellular rejection in their allografts upon autopsy. The remaining 2 monkeys showed severe cellular rejection on days 42 and 70 post-DBMT. Cytokine analysis suggested higher levels of pro-inflammatory markers in the lung transplant cohort, as compared to kidney recipients. CONCLUSION: Although the clinically applicable protocol showed success in kidney transplantation, the study did not show long-term survival in a lung transplant model, highlighting the organ-specific differences in tolerance induction.

Coronary artery bypass grafts to chronic occluded right coronary arteries.

Background: The benefit of revascularizing chronically occluded coronary arteries remains debatable, and available long-term outcome reports are sparse. Current guidelines recommend revascularization of chronically occluded arteries only in patients with myocardial ischemia and/or symptoms associated with angina. We investigated outcome of patients with total chronic occlusion of the right coronary artery (RCA) receiving coronary artery bypass grafting (CABG) surgery with and without revascularization of the RCA. Methods: We retrospectively analyzed all patients with chronically occluded RCAs receiving CABG with (group 1 = RCA-CABG; n = 487) and without (group 2 = No-RCA-CABG; n = 100) revascularization of the RCA. In total, 587 patients with complete follow-up of a minimum of 6 years were included (92%). Results: In total, 82% in group 1 versus 86% in group 2 were male (P = .38). European System for Cardiac Operative Risk Evaluation II was comparable between both groups (4.35 ± 7.09% vs 4.80 ± 5.77%, P = .56) with no major differences regarding preoperative characteristics between groups. Patients in group 1 received 3.24 ± 0.79 distal anastomoses, whereas group 2 received 2.45 ± 0.83 distal anastomoses (P < .001). Although in-hospital mortality was comparable (2.9% in group 1 vs 5.0% in group 2, P = .27), long-term survival was significantly better in group 1 (P = .002). No difference in the incidence of further major adverse cardiac and cerebrovascular events was found. Conclusions: Patients with a chronically occluded RCA undergoing CABG who did not receive an RCA graft showed a significantly reduced long-term survival. Given the herein presented data, revascularization of chronically occluded right arteries during CABG should be recommended whenever technically feasible.

Intraoperative Extracorporeal Circulatory Support in Lung Transplantation for Pulmonary Fibrosis.

BACKGROUND: Venous-arterial extracorporeal membrane oxygenation (ECMO) is an established technique for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Patients with pulmonary fibrosis have a higher risk to require it. The aim of this study was to identify risk factors for the need of intraoperative ECMO use. METHODS: Records of patients undergoing lung transplantation for pulmonary fibrosis at our institution between January 2010 and May 2018 were retrospectively reviewed. Univariate logistic regression analysis was used for statistical identification of risk factors. RESULTS: There were 105 patients (34%) who required intraoperative ECMO support (ECMO+ group), and 203 (66%) did not (ECMO- group). Preoperative proof of pulmonary hypertension was identified as a risk factor for intraoperative ECMO support (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2-6.5; P < .01). Revealed mean pulmonary arterial pressure values exceeding 50 mm Hg and pulmonary vascular resistance values exceeding 9.4 Wood units were identified as risk factors for the need of intraoperative ECMO use with a prediction probability of 70%. Increased recipient body surface area (OR, 0.2; 95% CI, 0.1-0.5; P < .01) emerged as a protective factor against intraoperative ECMO (Hosmer-Lemeshow statistic, P = .71) as well as higher cardiac output (OR, 0.7; 95% CI, 0.6-0.9; P < .01). The postoperative course was more complicated in the ECMO+ group, whereas survival at 5 years did not differ among groups (70% vs 69%, P = .79). CONCLUSIONS: Pulmonary hypertension with elevated pulmonary vascular resistance values predicts the need of intraoperative ECMO in patients receiving lung transplantation for pulmonary fibrosis. Although the postoperative course was more complicated in the ECMO+ group, long-term survival did not differ significantly.

Delayed non-myeloablative irradiation to induce long-term allograft acceptance in a large animal lung transplantation model.

We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative irradiation (7Gy thymus and 1.5Gy whole body IRR) before LTx and a perioperative donor specific splenocyte infusion (SpTx). Group 2 received perioperative SpTx but delayed IRR three days after LTx. Group 3 was exposed to delayed IRR without SpTx. Whereas 4 out of 7 animals from the non-delayed group never rejected their grafts and were electively sacrificed on postoperative day (POD) +500, all animals from group 2 rejected their grafts before POD 108. In group 3, 3 out of 8 animals developed long-term allograft acceptance. In all groups, donor leukocyte chimerism peaked up to 20% in peripheral blood one hour after reperfusion of the lung. Group 1 maintained prolonged chimerism beyond POD 7, whereas chimerism levels in groups 2 and 3 decreased continuously thereafter. Delayed irradiation has the potential to improve long-term graft survival, yet not as efficient as a perioperative conditioning protocol.

Long-term outcomes after intraoperative extracorporeal membrane oxygenation during lung transplantation.

INTRODUCTION: Over the past decade, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass (CPB) for cardiopulmonary support during lung transplantation at our institution. In this study, we present our experience using intraoperative ECMO in isolated lung transplantation and evaluate its impact on long-term graft function and survival. METHODS: All patients undergoing isolated lung transplantation with or without ECMO support between January 2010 and June 2019 were evaluated. Patients transplanted using CPB were excluded. Peri-operative and follow-up results from our database and patient charts were analyzed. Follow-up continued until September 1, 2019 (median, 3.34 years). RESULTS: In total, 311 of 1,161 lung transplant recipients (27%) received intraoperative ECMO, with 24 (2%) patients further requiring CPB. None of the remaining 826 (71%) patients required intraoperative cardiopulmonary support. ECMO patients exhibited higher pre-transplant surgical risk profiles and endured more complicated early post-operative courses than those without ECMO (in-hospital mortality, 10.9% vs 2.3%; p < 0.001). Inevitably, this resulted in poorer overall graft survival among ECMO recipients (p = 0.0025). However, correcting for patients surviving to hospital discharge, no difference in survival between groups was observed (5-year survival, 71% vs 72%; p = 0.56). Similarly, freedom from chronic lung allograft dysfunction, biopsy-confirmed cellular rejection, or need for pulsed-steroid therapy did not differ between the groups (p = 0.99, p = 0.78, and p = 0.93, respectively). CONCLUSIONS: Compared with patients not requiring cardiopulmonary support, ECMO recipients endured a more complicated peri-operative and early post-operative course. However, among those surviving to hospital discharge, no differences in long-term complications or outcomes were observed.

Long-Term Results of Bilateral Lung Transplantation in Patients With End-Stage Pulmonary Lymphangioleiomyomatosis.

INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare disease in women, leading to progressive deterioration of lung function and respiratory failure. We describe the outcome of patients with end-stage LAM who underwent lung transplantation at our center. MATERIALS AND METHODS: The records of patients with LAM transplanted at our institution between February 1997 and May 2015 were reviewed retrospectively. Morbidity and mortality were analyzed, and actuarial survival was calculated using Kaplan-Meier methods. The cumulative survival of transplant patients with LAM at our center was compared with survival after transplantation due to different diseases at our center and the results of the International Society for Heart and Lung Transplantation. Quality of life was assessed by a patient self-report at the end of the first postoperative year. RESULTS: During the study period, 25 patients underwent lung transplantation for LAM. All patients were women with a mean age of 50 (9) years. Thirteen patients (52%) had undergone previous thoracotomy. All patients (100%) received bilateral lung transplantation. One (4%) case of in-hospital mortality occurred and 9 (36%) late deaths. Two (8%) cases of late death were due to chronic lung allograft dysfunction. The 1-, 3-, and 5-year survival rates were 92%, 84%, and 76%, respectively. Quality-of-life ratings were above the normal in all eight 36-Item Short Form Health Survey subscales 1 year after transplantation. CONCLUSIONS: Lung transplantation offers a valuable therapy for patients with end-stage pulmonary LAM.

Transplant arteriosclerosis in humanized mice reflects chronic lung allograft dysfunction and is controlled by regulatory T cells.

OBJECTIVE: Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation limiting long-term survival. We studied correlations between CLAD after clinical lung transplantation and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. The pericardiophrenic artery was procured from surplus tissue of donor lungs (n = 22) transplanted in our clinical program and was implanted into the abdominal aorta of immune-deficient mice. METHODS: Allogeneic human peripheral blood mononuclear cells (PBMCs) had been procured 1 day after lung transplantation from the respective recipients with or without enriching for CD4+CD25high T cells were used. TA was assessed in mice 28 days later by histology. The respective clinical lung recipients were later divided into 2 groups. Eight patients (36.3%) had developed CLAD 23 ± 5 months after lung transplantation, whereas the remaining 14 (63.6%) did not develop CLAD within 25 ± 5 months. RESULTS: In the PBMC CLAD+ group of mouse experiments, TA was significantly more severe than in the PBMC CLAD- group (39.9% ± 13% vs 14.9% ± 4% intimal thickening; P = .0081). Then, intimal thickening was significantly inhibited in the PBMC+ regulatory T cells CLAD+ group compared with the PBMC CLAD+ group (0.4% ± 4% vs 39.9% ± 13%; P = .003). In the experiments using PBMCs from lung recipients without CLAD, enriching regulatory T cells also suppressed the development of TA (0.9% ± 3% PBMC CLAD- vs 14.9% ± 4% PBMC+ regulatory T cells CLAD-; P = .001). CONCLUSIONS: Lung transplant recipients who later develop CLAD have peripheral leukocytes already at the time of transplant that transfer proinflammatory properties leading to TA in a humanized mouse model. TA remains sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention of CLAD after lung transplantation.

Extended criteria donor lungs do not impact recipient outcomes in pediatric transplantation.

BACKGROUND: Pediatric lung transplantation remains the only curative treatment option for some end-stage lung diseases in childhood. Recipient numbers outnumber potential donor organs, and therefore a broader group of donor organs must be considered for pediatric lung transplantation. Herein we describe the outcome of utilizing extended criteria donor organs in pediatric lung transplantation. METHODS: A retrospective analysis was performed on all pediatric lung transplantations performed at the Hannover Medical School between April 2010 and December 2016. Donors were assigned to a group fulfilling standard donor criteria (International Society for Heart and Lung Transplantation [ISHLT] 2003) or not. Recipients' early- and mid-term morbidity and mortality were recorded. RESULTS: A total of 57 pediatric lung transplantations were performed: 27 donors fulfilled standard donor criteria (standard criteria donor [SCD] group) and 30 donors were extended criteria donors not fulfilling standard donor criteria (extended criteria donor [ECD] group). Pre-operative recipient characteristics, including age (median [IQR]: 14 [10‒15] vs 13 [10.8‒15] years, p = 0.71), underlying disease, admission to intensive care unit (37.0% vs 50%, p = 0.42), mechanical ventilation (14.8% vs 10.0%, p = 0.70), and extracorporeal membrane oxygenation (ECMO) support (11.1% vs 23.3%, p = 0.30) of both groups were similar. In the ECD group, more atypical volume reductions of the allograft were performed (0% vs 16.7%, p = 0.05), yet incidence of post-operative ECMO support was similar for the 2 groups. ECD recipients spent significantly less time on mechanical ventilation (median [IQR]: 2 [1‒2] vs 1 [1‒2] days, p = 0.04)] after surgery, but total intensive care unit stay and total hospital stay were similar between groups. Pulmonaryfunction testing results at discharge from initial hospital stay, after 1 year, and at last assessment were also similar. Freedom from chronic lung allograft dysfunction at 1 and 5years after transplantation showed no significant differences between groups. Survival rates up to 5years (67.9% vs 90.5%, p = 0.35) after transplantation were comparable between groups, yet, counterintuitively, long-term survival in the ECD group showed superior trends compared with the SCD group. CONCLUSIONS: ECD lungs can be used safely for pediatric lung transplantation without compromising short- and mid-term results.