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.

Oral Anticoagulants after Heart Transplantation-Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants.

AIMS: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. METHODS: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. RESULTS: A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan-Meier estimator. CONCLUSIONS: DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients.

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.

Lungs From Donors ≥70 Years of Age for Transplantation-Do Long-Term Outcomes Justify Their Use?

Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors <70 years of age and patients transplanted with lungs from donors ≥70 years of age. Among the 1,168 lung-transplanted patients, 62 patients received lungs from donors ≥70 years of age. The recipient age of those receiving older organs was significantly higher, and they were more likely to suffer from obstructive lung disease. Older donors were exposed to significantly shorter periods of mechanical ventilation prior to donation, had higher Horowitz indices, and were less likely to have smoked. The postoperative time on mechanical ventilation, time on ICU, and total hospital stay were comparable. The overall survival as well as CLAD-free survival showed no differences between both groups in the follow-up period. Utilization of lungs from donors ≥70 years of age leads to excellent mid- and long-term results that are similar to organs from younger donors when the organs from older donors are carefully preselected.

Lung transplantation despite preformed donor-specific antihuman leukocyte antigen antibodies: a 9-year single-center experience.

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P = .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P = .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients.

Immediate major dynamic changes in the T- and NK-cell subset composition after cardiac transplantation.

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4+ or CD8+ T cells and CD56dim CD16+ NK cells immediately after HTx linked to a decrease in naïve CD8+ and CM CD4+ T as well as CD56bright CD16- NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69+ CD25- and diminished CD69- CD25- CD4+ or CD8+ T-cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo-specific immune responses.

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.

Influence of Tricuspid Regurgitation After Heart Transplantation: A Single-center Experience.

Tricuspid valve regurgitation (TVR) is often observed after orthotopic heart transplantation. However, there is a scarcity of data regarding long-term outcomes of patients with TVR. Methods: Between January 2008 and December 2015, 169 patients underwent orthotopic heart transplantation at our center and were included in this study. TVR trends and associated clinical parameters were retrospectively analyzed. TVR was assessed after 30 d, 1 y, 3 y, and 5 y, and groups were defined according to changes in TVR grade: constant (group 1; n = 100), improvement (group 2; n = 26), and deterioration (group 3; n = 43). Survival, outcome with regard to operative technique, and long-term kidney and liver function during follow-up were assessed. Results: Mean follow-up time was 7.67 ± 4.17 y (median 8.62, Q1 5.06, Q3 11.16). Overall mortality was 42.0%, with differences between the groups (P < 0.01). Cox regression analysis revealed improvement of TVR as a significant predictor for survival (hazard ratio 0.23; 95% confidence interval, 0.08-0.63, P < 0.01). After 1 y 2.7%, after 3 y 3.7%, and after 5 y 3.9% of the patients showed persistent severe TVR. Creatinine levels after 30 d and 1, 3, and 5 y showed significant differences between the groups (P = 0.02, P < 0.01, P < 0.01, and P = 0.01), deterioration of TVR being associated with higher creatinine levels during follow-up. Conclusions: Deterioration of TVR is associated with higher mortality and renal dysfunction. Improvement of TVR may function as a positive predictor for long-term survival after heart transplantation. Improvement of TVR should be a therapeutic goal offering a prognostic value for long-term survival.

Frequency, Risk Factors, and Clinical Outcomes of Late-Onset Atrial Flutter in Patients after Heart Transplantation.

Aims: Atrial flutter (AFL) is a common late-onset complication after heart transplantation (HTX) and is associated with worse clinical outcomes. Methods: This study investigated the frequency, risk factors, and outcomes of late-onset post-transplant AFL. We analyzed 639 adult patients undergoing HTX at the Heidelberg Heart Center between 1989 and 2019. Patients were stratified by diagnosis and type of late-onset post-transplant AFL (>90 days after HTX). Results: A total of 55 patients (8.6%) were diagnosed with late-onset post-transplant AFL, 30 had typical AFL (54.5%) and 25 had atypical AFL (45.5%). Patients with AFL were younger at HTX (p = 0.028), received more biatrial anastomosis (p = 0.001), and presented with moderate or severe tricuspid regurgitation (56.4%). Typical AFL was associated with graft rejection (p = 0.016), whereas atypical AFL was associated with coronary artery disease (p = 0.028) and stent implantation (p = 0.042). Patients with atypical AFL showed a higher all-cause 1-year mortality (p = 0.010) along with a higher rate of graft failure after diagnosis of AFL (p = 0.023). Recurrence of AFL was high (83.6%). Patients with catheter ablation after AFL recurrence had a higher 1-year freedom from AFL (p = 0.003). Conclusions: Patients with late-onset post-transplant AFL were younger at HTX, received more biatrial anastomosis, and showed a higher rate of moderate or severe tricuspid regurgitation. Typical AFL was associated with graft rejection, whereas atypical AFL was associated with myocardial ischemia, graft failure, and mortality. Catheter ablation represents a viable option to avoid further episodes of late-onset AFL after HTX.

Wound Infections in Adult Patients after Berlin Heart® EXCOR Biventricular Assist Device Implantation.

The Berlin Heart® EXCOR is a paracorporeal, pulsatile ventricular assist device used in patients of all age groups. However, adolescent and adult patients on EXCOR support are scarcely explored. Herein, we present a detailed description of infectious complications in this patient cohort. From 2006 to 2020, 58 patients received a biventricular assist device (BiVAD) at our institution and were included in this study. Postoperative infections were assessed after BiVAD implantation and subsequent heart transplantation (HTx). A Berlin Heart® EXCOR BiVAD was implanted as a bridge to transplantation in 58 patients (12-64 years). Most patients were INTERMACS I, and their median age was 49 years. Wound infections (WI) specific to the ventricular assist device (VAD) occurred in 31 (53.4%) patients with a mean time of 113 ± 155 days after BiVAD implantation. HTx was performed in 30 (51.7%) patients and thereof 10 (33.3%) patients developed at least one WI post-HTx. The mean time of WI after HTx was 17 ± 14 days. In four cases, WIs were caused by the same pathogen as before HTx. According to our institutional BiVAD wound classification, the mean wound score was 3. The VAD-specific wound infections were manageable and did not increase mortality nor precluded HTx in Berlin Heart® EXCOR patients. No specific risk factors for VAD-specific wound infections could be identified.

Long-Term Patency of Venous Conduits Targeting the Right Coronary Artery System-Single Is Superior to Sequential bypass Grafting.

Objective: Little is known about the fate of bypass grafts to the right coronary system. To investigate the long-term patency of venous bypass grafts directed to the right coronary artery (RCA) based on postoperative angiograms and to identify predictors of graft occlusion. Methods: In this single-center study, all patients who underwent coronary angiography from 2005 to 2021 after previously undergoing isolated coronary artery bypass grafting (CABG) were included. The primary endpoint was graft occlusion over a median follow-up of 9.1 years. Results: Among a total of 1106 patients (17.0% women, 64 (57−71) years median age), 289 (26.1%) received a sequential vein graft and 798 (72.2%) a single graft. Multivariate regression revealed age (HR 1.019, CI 95% 1.007−1.032), the urgency of CABG (HR 1.355, CI 95% 1.108−1.656), and severely impaired left ventricular function (HR 1.883, CI 95% 1.290−2.748), but not gender and chronic total occlusion (CTO) as predictive factors for graft occlusion. Single conduits were found to be a predictor of graft patency (HR 0.575 CI 95% 0.449−0.737). The angiographic outcome showed an overall 10-year freedom from graft occlusion of 73.4% ± 1.6%. The 5-year (10-year) freedom from graft occlusion was 76.9% ± 2.8% (57.8% ± 4.0%) for sequential grafts and 90.4% ± 1.1% (77.8% ± 1.7%) for single grafts (log-rank p < 0.001). Conclusions: In symptomatic patients with renewed angiography, venous bypass grafting of the RCA showed acceptable long-term patency rates. Single bypass grafting of the RCA was superior to sequential grafting, which needs to be further investigated.

Pre-transplant Type 2 Diabetes Mellitus Is Associated With Higher Graft Failure and Increased 5-Year Mortality After Heart Transplantation.

Aims: Cardiac transplant recipients often suffer from type 2 diabetes mellitus (T2DM) but its influence on graft failure and post-transplant mortality remains unknown. The aim of this study was to investigate the long-term effects of pre-transplant T2DM in patients after heart transplantation (HTX). Methods: This study included a total of 376 adult patients who received HTX at Heidelberg Heart Center between 01/01/2000 and 01/10/2016. HTX recipients were stratified by diagnosis of T2DM at the time of HTX. Patients with T2DM were further subdivided by hemoglobin A1c (HbA1c ≥ 7.0%). Analysis included donor and recipient data, immunosuppressive drugs, concomitant medications, post-transplant mortality, and causes of death. Five-year post-transplant mortality was further assessed by multivariate analysis (Cox regression) and Kaplan-Meier estimator. Results: About one-third of all HTX recipients had T2DM (121 of 376 [32.2%]). Patients with T2DM showed an increased 5-year post-transplant mortality (41.3% versus 29.8%; P = 0.027) and had a higher percentage of death due to graft failure (14.9% versus 7.8%; P = 0.035). Multivariate analysis showed T2DM (HR: 1.563; 95% CI: 1.053-2.319; P = 0.027) as an independent risk factor for 5-year mortality after HTX. Kaplan-Meier analysis showed a significantly better 5-year post-transplant survival of patients with T2DM and a HbA1c < 7.0% than patients with T2DM and a HbA1c ≥ 7.0% (68.7% versus 46.3%; P = 0.008) emphasizing the clinical relevance of a well-controlled T2DM in HTX recipients. Conclusion: Pre-transplant T2DM is associated with higher graft failure and increased 5-year mortality after HTX.

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.

Identification of distinct secretory patterns and their regulatory networks of ischemia versus reperfusion phases in clinical heart transplantation.

BACKGROUND: Ischemia/reperfusion injury (IRI) is associated with inflammatory responses contributing to the development of primary graft dysfunction (PGD) and rejection. Here, we investigated the pathophysiology of IRI and the early phase after heart transplantation (HTx) regarding its cytokine/chemokine and endothelial networks. METHODS: Using multiplex technology, we assessed protein concentrations in plasma samples of HTx recipients (n = 11) pre-, postoperatively, 24 h and 3 weeks after HTx. The same proteins were quantified in organ storage solutions at the end of heart storage (n = 10). Unsupervised cluster, principal component analysis (PCA), K-nearest neighbor (KNN) network classifier analysis, ANOVA and Spearman correlation analyses were performed to identify specific patterns for IRI and individual kinetics of important soluble factors in HTx. RESULTS: Unique patterns of soluble factors were identified in plasma of HTx patients. KNN analysis defined IL-10, IL-6, sIL-6Rα, IL-1RA, IL-16, sVEGFR-1, IGFBP-1, HGF and sHer-2 as strongest signals directly post-Tx declining 24 hrs after HTx. By contrast, MIF, osteopontin (OPN), sVCAM-1 and sICAM-1, IGFBP-1, SCGF-ß, HGF were highly enriched in organ storage solutions, reflecting distinct ischemic (storage solution) vs. reperfusion (plasma) signatures. CONCLUSIONS: We identified specific inflammatory signatures for ischemic vs. reperfusion phases of HTx, associated with pro- as well as anti-inflammatory and endothelial biomarker candidates for IRI. These signatures might help to identify potential danger factors and their networks at both the ex situ (ischemic) as well as the reperfusion phase in the recipient after implantation.