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Background: Regulatory T cell (Treg) therapy is a promising approach to amelioration of allograft rejection and promotion of organ transplant tolerance. However, the fate of infused Treg, and how this relates to their therapeutic efficacy using different immunosuppressive regimens is poorly understood. Our aim was to analyze the tissue distribution, persistence, replicative activity and phenotypic stability of autologous, donor antigen alloreactive Treg (darTreg) in anti-thymocyte globulin (ATG)-lymphodepleted, heart-allografted cynomolgus monkeys., Methods: darTreg were expanded ex vivo from flow-sorted, circulating Treg using activated donor B cells and infused posttransplant into recipients of major histocompatibility complex-mismatched heart allografts. Fluorochrome-labeled darTreg were identified and characterized in peripheral blood, lymphoid, and nonlymphoid tissues and the graft by flow cytometric analysis., Results: darTreg selectively suppressed autologous T cell responses to donor antigens in vitro. However, following their adoptive transfer after transplantation, graft survival was not prolonged. Early (within 2 wk posttransplant; under ATG, tacrolimus, and anti-IL-6R) or delayed (6-8 wk posttransplant; under rapamycin) darTreg infusion resulted in a rapid decline in transferred darTreg in peripheral blood. Following their early or delayed infusion, labeled cells were evident in lymphoid and nonlymphoid organs and the graft at low percentages (<4% CD4+ T cells). Notably, infused darTreg showed reduced expression of immunoregulatory molecules (Foxp3 and CTLA4), Helios, the proliferative marker Ki67 and antiapoptotic Bcl2, compared with preinfusion darTreg and endogenous CD4+CD25hi Treg., Conclusions: Lack of therapeutic efficacy of infused darTreg in lymphodepleted heart graft recipients appears to reflect loss of a regulatory signature and proliferative and survival capacity shortly after infusion., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Congestive heart failure patients have hepatic congestion and abnormal coagulation profiles, increasing perioperative bleeding at time of ventricular assist device implantation. This study examined the impact of the preoperative administration of vitamin K on perioperative blood transfusion requirements., Methods: Retrospectively, 190 patients met inclusion criteria. Patients received no vitamin K (n = 62) or two 10-mg doses of intravenous vitamin K (n = 128) in the 24 hours before assist device implantation. Primary end points included transfusion requirements and reexploration rates for bleeding. Secondary outcomes were pump thrombosis and in-hospital mortality., Results: Baseline characteristics were similar between the 2 groups, with slight differences (not statistically significant) noted in the Interagency Registry for Mechanically Assisted Circulatory Support profile and total bilirubin levels. The only significant difference noted was the year of implantation (P < .001). Blood product usage was significantly lower in the vitamin K group compared to the no vitamin K group (P < .001). Higher rates of reexploration for bleeding (29.7% vs 13.6%, P = .023) and death at hospital discharge (16.2% vs 2.8%, P = .004) were noted for the no vitamin K group compared with the vitamin K group. After adjusting for age, sex, race, body mass index, Interagency Registry for Mechanically Assisted Circulatory Support profile, total bilirubin, surgeon, and year of operation, reexploration rates and death did not achieve statistical significance. No statistically significant difference was observed in stroke and pump thrombosis rates between the 2 groups., Conclusions: Preoperative vitamin K administration may help reduce blood product use without any increased risk for strokes or pump thrombosis., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Right heart failure (RHF) following left ventricular assist device (LVAD) implantation increases morbidity and mortality for those who develop this complication. The purpose of this study was to assess the differences in incidence of RHF and outcomes between 2 types of continuous-flow LVADs at a single center. Methods: From January 2012 through June 2016, 184 patients were implanted with a continuous-flow LVAD (161 patients with the HeartMate II and 23 patients with the HeartWare device) either as a bridge to transplant or as destination therapy. Preoperative demographics, medical history, laboratory values, hemodynamics, and device type were analyzed to determine the variables associated with RHF and mortality. Results: Preoperative variables between the 2 groups were homogeneous. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (92%) and New York Heart Association class IV (81%). More patients in the HeartMate II group had the indication of destination therapy (54% vs 30%), while more patients in the HeartWare group were implanted as bridge to transplant (70% vs 46%). RHF occurred in 57% of HeartWare patients compared to 16% of patients who received the HeartMate II ( P =0.0001). After propensity score analysis, patients receiving the HeartWare device had increased odds for RHF ( P =0.0013) and renal failure requiring dialysis ( P =0.0135). The HeartMate II patient survival rate exceeded the HeartWare patient survival rate at 1 year (82.1% vs 67.2%) and at 2 years (74.6% vs 61.7%), but this difference did not achieve statistical significance (log-rank P =0.087). Conclusion: These results indicate that device type may affect RHF incidence and mortality. Studies at other centers are needed to replicate these findings.

The impact of cardiac resynchronization therapy (CRT) on clinical outcome in patients with a continuous-flow left ventricular assist device (LVAD) is currently not well understood. We conducted a systematic literature review and meta-analysis with an intention to summarize all published clinical evidence. We searched MEDLINE and EMBASE databases through March 2018 for studies that compared the outcomes in patients with LVAD and CRT. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effects model, inverse variance method. The between-study heterogeneity was assessed using the Q statistic and I 2 . A total of seven studies that included 1157 (575 CRT; 582 non-CRT) patients were identified. Our meta-analysis did not demonstrate a significant difference in the risk of mortality (pooled OR = 1.21, 95% CI 0.90-1.63, P = 0.21), ventricular arrhythmia incidence (pooled OR = 1.36, 95% CI 0.99-1.86, P = 0.06), hospitalization (pooled OR = 1.36, 95% CI 0.59-3.14, P = 0.48), or implantable cardioverter defibrillator therapies (pooled OR = 1.08, 95% CI 0.51-2.30, P = 0.84) among the CRT group compared with the non-CRT group. There was high heterogeneity with an I 2 of 75% for ICD therapies. Among LVAD patients, CRT combined did not significantly affect mortality, re-hospitalization, ventricular arrhythmia incidence, and ICD therapies.

Background: The general goals of endovascular management in chronic distal thoracic aortic dissection are optimizing the true lumen, maintaining branch patency, and promoting false lumen (FL) thrombosis. Distal seal can be challenging in chronic distal thoracic aortic dissection due to the well-established secondary fenestrations and fibrotic septum. We describe our approach of distal landing zone optimization (DLZO) to enable full-diameter contact of the distal endoprosthesis., Materials and Methods: Our experience includes 19 procedures in 16 patients (12 male, age 68 ± 8 years) between May 2014 and November 2017. A history of previous ascending repair for type A dissection was present in 8 patients. Treatment indication was enlarging aneurysm in all subjects, and 4 patients had associated chronic visceral or distal ischemia. Point septal fenestrations were expanded by serial balloon dilation and/or wire-pull approaches. Balloon molding was used to ensure complete endograft apposition and FL collapse., Results: One death occurred due to aortic perforation during wire-pull fenestration in a patient with heavily calcified and angulated aorta. The remaining procedures were accomplished safely and successfully. Balloon fenestration was used in 16 procedures, alone or in combination with a limited wire pull component. Adjunct procedures for distal seal included surgeon-modified fenestrated stent graft (3), iliac branch device (3), parallel superior mesenteric artery stent-graft (1), renal artery or superior mesenteric artery stent-graft (4), iliac stent (3), and plug obliteration of FL (5). Reintervention was required in 3 patients due to delayed loss of seal after the initial procedure (3, 8, and 12 months). Two were managed by repeat DLZO and distal extension. The third had distal extension via a surgeon-modified fenestrated stent-graft component. Follow-up imaging was available in 14 patients (16.0 ± 12.5 months, range: 1-33), with stable or regressed sac diameter with complete or near-complete thrombosis of the FL in all patients., Conclusions: DLZO enabled creation of a distal seal zone in all patients. Residual retrograde filling of the FL is a marker of procedure failure, especially when seal segment length or feasible endoprosthesis oversizing are marginal. Insufficient landing segment can be circumvented with the use of a fenestrated or branched device to accomplish seal in the visceral aorta or iliac bifurcation. Adjunct FL ablation is also a valuable technique to promote FL thrombosis., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We report the first case of a ruptured intracranial aneurysm-related Staphylococcus epidermidis bacteremia in a patient supported by a continuous flow left ventricular assist device (LVAD). Mycotic aneurysms (MAs) are aneurysmal degeneration of the arterial wall as a result of infection. Current recommendations for management of intracranial mycotic aneurysms are based on a few retrospective case studies. There are only a few cases of intracranial MA reported in patients with LVAD infections caused by Pseudomonas aeruginosa and Klebsiella rhinos. Here, we describe the first case of a ruptured intracranial aneurysm caused by a less virulent organism (Staphylococcus epidermidis) and conclude that screening for asymptomatic MA should be strongly considered in patients with persistent LVAD- and implantable cardiac defibrillator pacemaker-associated infections., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine if indication for support affects the outcomes after temporary right ventricular mechanical circulatory support after postcardiotomy cardiogenic shock, cardiac transplant, or left ventricular assist device placement., Methods: A retrospective review was performed on 80 patients receiving a right ventricular assist device. Data were collected from a prospectively maintained database. Kaplan-Meier survival analysis was performed to compare survival between groups. Multivariate regression analysis was performed to identify risk factors for failure to wean from support., Results: The indication for support was postcardiotomy cardiogenic shock in 13 patients (16%), cardiac transplant in 25 patients (31%), and left ventricular assist device in 42 patients (53%). Median support time was 6 days. Device was successfully weaned in 6 postcardiotomy cardiogenic shock cases (46%), 21 cardiac transplant cases (84%), and 35 left ventricular assist device cases (83%). Survival was worse for patients with postcardiotomy cardiogenic shock compared with patients with a left ventricular assist device. Survival up to 3 months was better for patients who received immediate (n = 43) versus delayed (n = 37) support (79% vs 46%, P = .003). Weaning and survival remained static across implant era. Risk factor analysis identified postcardiotomy cardiogenic shock indication (odds ratio, 0.161; P = .007; confidence interval, 0.043-0.600) as an independent negative predictor of weaning from mechanical support., Conclusions: Temporary right ventricular mechanical support remains an effective treatment strategy after left ventricular assist device placement with immediate support resulting in superior short-term survival. Caution should be applied in postcardiotomy cardiogenic shock when weaning and survival are poor. Overall survival outcomes have remained relatively static over time., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Pump thrombosis (PT) is a dreaded complication after left ventricular assist device (LVAD) implantation. Problems with inflow cannula (IC) position may precipitate thrombus development. We sought to determine if IC position contributes to the development of PT., Methods: We conducted a retrospective review of 76 HeartMate II LVAD implants. The angle of the IC (AIC) to the horizontal plane was measured on chest x-rays. Patients who developed PT (PT group) were compared to the remaining patients (control group)., Results: The mean age at implantation was 56 ± 14 years, and 82% of the patients were male. Ten patients (13%) developed PT. Six (60%) required device exchange, and 4 (40%) were managed with anticoagulation and/or thrombolysis. The median AIC for all patients at implantation was 59° (range, 38°-98°; 25th-75th interquartile range, 50°-75°). In the PT group, the median AIC was larger at the time of PT diagnosis compared to implantation (70° vs 60°, P = 0.005). In the control group, the median AIC was also larger at follow-up compared to implantation (61° vs 58°, P < 0.001) although to a lesser degree than in the PT group. No difference was seen in the median AIC between the PT group and the control group at implantation (60° vs 58°, respectively; P = 0.668) or at follow-up (70° vs 61°, respectively; P = 0.309). However, the median AIC at follow-up in the PT group was significantly larger than the median AIC at implantation in the control group (70° vs 58°, respectively; P = 0.014)., Conclusion: The HeartMate II LVAD IC position contributes to the development of PT. Regular monitoring of cannula position may help identify patients at risk for this problem.

Objective: To identify preoperative predictors of extracorporeal support in patients with pulmonary hypertension (PH) undergoing bilateral sequential lung transplantation (LTx), and to examine outcomes associated with the use of extracorporeal support., Design: Retrospective, observational study., Setting: Single organ transplantation and tertiary care university medical center., Participants: Adults with PH (preoperative mean pulmonary artery pressure (mPAP)≥25 mmHg) who underwent primary bilateral sequential LTx during 2007 to 2013., Measurements and Main Results: Of 262 patients with PH undergoing LTx, extracorporeal support was initiated intraoperatively in 149 (57%). Preoperative severe right ventricle (RV) dysfunction and moderate or severe tricuspid regurgitation (TR) were associated with extracorporeal support. In the remaining 208 patients without those factors, increasing preoperative oxygen requirement (odds ratio [OR] 1.30 per 1 L/min, 95% confidence intervals [CI] 1.11-1.52, p = 0.001), presence of RV dilation (OR 2.77, 95% CI 1.28-6.02, p = 0.010), and mPAP (OR 1.33 per 5-mmHg increase in mPAP, 95% CI 1.04-1.70, p = 0.021) were associated independently with extracorporeal support in the multivariable model. Analysis of 49 propensity-matched pairs showed longer intensive care unit (5 v 14 days, p = 0.006) and hospital stays (27 v 39 days, p = 0.016) and increased need for tracheostomy (16% v 41%, p = 0.017) in patients exposed to extracorporeal support but no differences in 30-day mortality, stroke, myocardial infarction, or dialysis., Conclusions: Severity of RV dysfunction, TR, RV dilatation, increasing oxygen requirement, and increasing mPAP showed significant associations with the need for extracorporeal support during LTX in patients with PH. Extracorporeal support was associated with increased length of stay and tracheostomy but not with mortality or other complications. © 2016 Elsevier Inc. All rights reserved., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Adult lung transplant recipients with small chests have traditionally received lungs from pediatric donors, placing an additional strain on the already restricted pediatric donor pool. Performing lobar lung transplantation (LLT) can circumvent issues with donor-recipient size mismatch; however, LLT imparts additional risks. Here, we review our experience using LLT and standard lung transplantation using a pediatric donor (PDLT) for adults with small chests., Methods: We retrospectively reviewed consecutive patients with end-stage lung disease and a height of 65 inches or less who underwent LLT (n = 15) or PDLT (n = 15) between 2006 and 2012 at our institution, a high-volume lung transplant center., Results: Lobar lung transplantation recipients were older (54 ± 10 vs 48 ± 8 years) and had higher pulmonary pressure (57 ± 11 vs 52 ± 27 mmHg) and higher lung allocation scores (70 ± 9 vs 51 ± 8) than PDLT recipients (all P < 0.05). Mean waiting time was 62 days for PDLT and 9 days for LLT. Postoperatively, the incidence of severe primary graft dysfunction and the incidence of acute renal insufficiency were higher, and the mean intensive care unit stay was longer in the LLT group, but the incidence of bronchial anastomotic complications was higher in the PDLT group because of significant size discrepancy in the main bronchus (P < 0.05). Interestingly, long-term functional outcomes and survival rates were similar between the groups., Conclusions: Both LLT and PDLT are viable surgical options for adult patients with small chests. Because of the potential impact on posttransplant outcomes, the technical complexity of transplantation, decisions regarding the best surgical approach should be made by experienced surgeons.

Background: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach., Methods: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography., Results: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care., Conclusion: Minimally invasive LVAD therapy using the Impella 5.0 via the RSA cutdown is an attractive option in acute on chronic decompensated heart failure. Improvement in end organ function allows for transition to recovery or to advanced surgical therapies such as permanent LVAD and heart transplantation. Significant advantages to this approach include improved left ventricular unloading, lower anticoagulation need, and the potential for ambulation and physical therapy.

The ability of regulatory T cells (Treg) to prolong allograft survival and promote transplant tolerance in lymphodepleted rodents is well established. Few studies, however, have addressed the therapeutic potential of adoptively transferred, CD4(+) CD25(+) CD127(-) Foxp3(+) (Treg) in clinically relevant large animal models. We infused ex vivo-expanded, functionally stable, nonselected Treg (up to a maximum cumulative dose of 1.87 billion cells) into antithymocyte globulin-lymphodepleted, MHC-mismatched cynomolgus monkey heart graft recipients before homeostatic recovery of effector T cells. The monkeys also received tacrolimus, anti-interleukin-6 receptor monoclonal antibodies and tapered rapamycin maintenance therapy. Treg administration in single or multiple doses during the early postsurgical period (up to 1 month posttransplantation), when host T cells were profoundly depleted, resulted in inferior graft function compared with controls. This was accompanied by increased incidences of effector memory T cells, enhanced interferon-γ production by host CD8(+) T cells, elevated levels of proinflammatory cytokines, and antidonor alloantibodies. The findings caution against infusion of Treg during the early posttransplantation period after lymphodepletion. Despite marked but transient increases in Treg relative to endogenous effector T cells and use of reputed "Treg-friendly" agents, the host environment/immune effector mechanisms instigated under these conditions can perturb rather than favor the potential therapeutic efficacy of adoptively transferred Treg., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

If pig hearts could be transplanted successfully into patients with end-stage cardiac failure, the critical shortage of hearts from deceased human donors would be overcome. The several attempts at cardiac xenotransplantation carried out in the 20th century, usually with hearts from nonhuman primates (NHPs), are reviewed, as are the surgical techniques used in experimental heart transplantation in animals. For a number of reasons, the pig has been selected as the potential source of organs for clinical transplantation. The major pathobiological barriers that the pig presents, and progress in overcoming these barriers either by genetic engineering of the pig or by the administration of novel immunosuppressive agents, are described. Currently, non-life-supporting pig heterotopic heart transplantation in NHPs has extended to more than 2 years in 1 case, with life-supporting orthotopic heart transplantation of almost 2 months. Future approaches to resolve the remaining problems and the selection of patients for the initial clinical trials are briefly discussed., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Increasing use of left ventricular assist devices (LVADs) has been accompanied by rising incidence of gastrointestinal bleeding (GIB). Objectives of this study were to determine the yearly incidence of GIB in LVAD recipients, compare outcomes of continuous-flow (CF) and pulsatile-flow LVAD eras, and investigate for risk factors. The Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database from 2005 to 2010 was analyzed. Primary outcome of interest was incidence of GIB in LVAD recipients. Multivariate logistic regression model was used to examine independent associations of GIB with risk factors and outcomes. An estimated 8,879 LVAD index admissions and 8,722 readmissions in LVAD recipients over 6 years were analyzed. The yearly incidence of GIB after LVAD implantation increased from 5% in 2005 to 10% in 2010. On multivariate regression analysis, the odds of GIB was 3.24 times greater (95% confidence interval 1.53 to 6.89) in the era of CF LVADs than in the era of pulsatile-flow LVADs. Compared to their younger counterparts, in LVAD recipients aged >65 years, the adjusted odds of GIB was 20.5 times greater (95% confidence interval 2.24 to 188). GIB did not significantly increase the inhospital mortality but increased the inpatient length of stay. In conclusion, the incidence of GIB in LVAD recipients has increased since the use of CF LVADs has increased, leading to greater inpatient lengths of stay and hospital charges. Older recipients of CF LVADs appear to be at a greater risk of GIB., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: In pig-to-baboon heart/artery patch transplantation models, adequate costimulation blockade prevents a T-cell response. After heart transplantation, coagulation dysfunction (thrombocytopenia, reduced fibrinogen, increased D-dimer) and inflammation (increased C-reactive protein [CRP]) develop. We evaluated whether coagulation dysfunction and/or inflammation can be detected following pig artery patch transplantation., Methods: Baboons received heart (n = 8) or artery patch (n = 16) transplants from genetically engineered pigs and a costimulation blockade-based regimen. Heart grafts functioned for 15-130 days. Artery recipients were euthanized after 28-84 days. Platelet counts, fibrinogen, D-dimer, and CRP were measured., Results: Thrombocytopenia and reduced fibrinogen developed only in recipients of hearts not expressing a coagulation-regulatory protein (n = 4), but not in other heart or patch recipients. However, in heart recipients (n = 8), there were sustained increases in D-dimer (<0.5 to 1.9 ug/ml [P < 0.01]) and CRP (0.26-2.2 mg/dl [P < 0.01]). In recipients of artery patches, there were also sustained increases in D-dimer (<0.5 to 1.4 ug/ml [P < 0.01]) and CRP (0.26 to 1.5 mg/dl [P < 0.001]). An IL-6R antagonist suppressed the increase in CRP, but not D-dimer., Conclusion: The pig artery patch model has proved valuable for determining immunosuppressive regimens that prevent sensitization to pig antigens. This model also provides information on the sustained systemic inflammation in xenograft recipients (SIXR). An IL-6R antagonist may help suppress this response., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mechanical ventilation (MV) is an important aspect in the intraoperative and early postoperative management of lung transplant (LTx)-recipients. There are no randomized-controlled trials of LTx-recipient MV strategies; however there are LTx center experiences and international survey studies reported. The main early complication of LTx is primary graft dysfunction (PGD), which is similar to the adult respiratory distress syndrome (ARDS). We aim to summarize information pertinent to LTx-MV, as well as PGD, ARDS, and intraoperative MV and to synthesize these available data into recommendations. Based on the available evidence, we recommend lung-protective MV with low-tidal-volumes (≤6 mL/kg predicted body weight [PBW]) and positive end-expiratory pressure for the LTx-recipient. In our opinion, the MV strategy should be based on donor characteristics (donor PBW as a parameter of actual allograft size), rather than based on recipient characteristics; however this donor-characteristics-based protective MV is based on indirect evidence and requires validation in prospective clinical studies.

The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: Preoperative liver dysfunction may influence haemostasis following ventricular assist device (VAD) implantation. The Model for End-stage Liver Disease (MELD) score was assessed as a predictor of bleeding and levels of haemostatic markers in patients with currently utilized VADs., Methods: Sixty-three patients (31 HeartMate II, 15 HeartWare, 17 Thoratec paracorporeal ventricular assist device) implanted 2001-11 were analysed for preoperative liver dysfunction (MELD) and blood product administration. Of these patients, 21 had additional blood drawn to measure haemostatic marker levels. Cohorts were defined based on high (≥18.0, n = 7) and low (<18.0, n = 14) preoperative MELD scores., Results: MELD score was positively correlated with postoperative administration of red blood cell (RBC), platelet, plasma and total blood product units (TBPU) , as well as chest tube drainage and cardiopulmonary bypass time. Age and MELD were preoperative predictors of TBPU by multivariate analysis. The high-MELD cohort had higher administration of TBPU, RBC and platelet units and chest tube drainage postimplant. Similarly, patients who experienced at least one bleeding adverse event were more likely to have had a high preoperative MELD. The high-MELD group exhibited different temporal trends in F1 + 2 levels and platelet counts to postoperative day (POD) 55. D-dimer levels in high-MELD patients became elevated versus those for low-MELD patients on POD 55., Conclusions: Preoperative MELD score predicts postoperative bleeding in contemporary VADs. Preoperative liver dysfunction may also alter postoperative subclinical haemostasis through different temporal trends of thrombin generation and platelet counts, as well as protracted fibrinolysis., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy., Methods: As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept + anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered., Results: When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response., Conclusion: Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: With an increasing number of potential recipients and a comparatively static number of donors, lung transplantation (LT) in the elderly has come under significant scrutiny. Previous studies have been limited by single-center experiences with small population sizes and often mixed results. Using a national registry, we sought to evaluate the following: (1) differences in survival outcomes in septuagenarians compared with sexagenarians; and (2) the effect of temporal trends on the development of other comorbidities in this population., Methods: We analyzed the Scientific Registry of Transplant Recipients (SRTR) data files from the United Network for Organ Sharing (UNOS) database to identify recipients who underwent LT between the years 2000 and 2013. The study period was divided into two equal eras. Using Kaplan-Meier analysis, we compared the 30-day, 3-month, 1-year, 3-year and 5-year patient survival between septuagenarians and sexagenarians in both eras. Separate multivariate analyses were performed to estimate the risk of renal failure, risk of rejection and length of hospital stay (LOS) post-LT in each of these time periods., Results: A total of 6,596 patients were identified comprising 1,726 (26.2%) during 2000 to 2005 and 4,870 (73.8%) during 2006 to 2012. In the "early era," 32 (1.9%) septuagenarians and 1,694 (98.1%) sexagenarians underwent LT, whereas 543 (11.1%) septuagenarians and 4,327 (88.9%) sexagenarians underwent transplantation in the "latter era." A comparison of patient survival between the two groups in the early era revealed no difference at 30 days (95.7% vs 93.8%, p = 0.65). However, 3-month (91.2% vs 75%, p = 0.04) and 1-year patient survival (79.5% vs 62.5%, p = 0.048) were both lower in the septuagenarian group. In the later era, however, there were no differences in 30-day (96.2% vs 96.8, p = 0.5), 3-month (92.7% vs 91.9%, p = 0.56) or 1-year (81.7% vs 78.6%, p = 0.12) patient survival between the two age groups. Survival rates at 3 years (63.7% vs 49.3%, p < 0.001) and 5 years (47.5% vs 28.2%, p < 0.001) were each significantly lower in the septuagenarian group., Conclusion: Overall, LT outcomes for the elderly have improved significantly over time and early outcomes in the modern era rival those found in younger recipients., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Improvements in technology have led to a resurgence in the use of extracorporeal membrane oxygenation as a bridge to lung transplantation. By using a national registry, we sought to evaluate how short-term survival has evolved using this strategy., Methods: With the use of the United Network for Organ Sharing database, we analyzed data from 12,458 adults who underwent lung transplantation between 2000 and 2011. Patients were categorized into 2 cohorts: 119 patients who were bridged to transplantation using extracorporeal membrane oxygenation and 12,339 patients who were not. The study period was divided into four 3-year intervals: 2000 to 2002, 2003 to 2005, 2006 to 2008, and 2009 to 2011. With Kaplan-Meier analysis, 1-year survival was compared for the 2 cohorts of patients in each of the time periods. A propensity score-adjusted Cox regression model was used to estimate the risk of 1-year mortality., Results: Of the total number of recipients, 4 (3.4%) were bridged between 2000 and 2002, 17 (14.3%) were bridged between 2003 and 2005, 31 (26.1%) were bridged between 2006 and 2008, and 67 were bridged (56.3%) between 2009 and 2011. Recipients bridged using extracorporeal membrane oxygenation were more likely to be younger and diabetic and to have higher serum creatinine and bilirubin levels. The 1-year survival for those bridged with extracorporeal membrane oxygenation was significantly lower in subsequent periods: 25.0% versus 81.0% (2000-2002), 47.1% versus 84.2% (2006-2008), and 74.4% versus 85.7% (2009-2011). However, this survival progressively increased with each period, as did the number of patients bridged using extracorporeal membrane oxygenation., Conclusions: Short-term survival with the use of extracorporeal membrane oxygenation as a bridge to lung transplantation has significantly improved over the past few years., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The intraoperative use of cardiopulmonary bypass (CPB) in lung transplantation has been associated with increased rates of pulmonary dysfunction and bleeding complications. More recently, extracorporeal membrane oxygenation (ECMO) has emerged as a valid alternative method of support and has been our preferred method of support since March 2012. We compared early and midterm outcomes of these 2 support methods., Methods: Between July 2007 and April 2013, 271 consecutive patients underwent lung transplant using CPB (n = 222) or ECMO (n = 49). We retrospectively reviewed the outcomes of these patients requiring CPB or ECMO during lung transplant., Results: The CPB and ECMO groups had comparable demographic and operative characteristics; however, the ECMO group had higher mean lung allocation scores (73 vs 52, p < 0.001). In the CPB group, more patients required reintubation (35.6% vs 20.4%, p = 0.04) or temporary tracheostomy (44.6% vs 28.6%, p = 0.05). Patients in the CPB group had a higher rate of renal failure requiring dialysis than the ECMO group (22.1% vs 8.2 %, p = 0.028). There were no differences in severe PGD requiring postoperative circulatory support (p = 0.83) or the need for perioperative red blood cell transfusions (p = 0.64) between the groups. No differences in 30-day (5% CPB vs 4.1% ECMO) or 6-month mortality (14.4% CPB vs 14.3% ECMO) were noted., Conclusions: The use of ECMO in lung transplant is safe and in our experience was associated with decreased rates of pulmonary and renal complications, as compared with CPB. Extracorporeal membrane oxygenation has become our preferred method of intraoperative support during lung transplantation., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: A shortage of donors has compelled the use of extended-criteria donor organs in lung transplantation. The purpose of this study was to evaluate the impact of using older donors on outcomes after lung transplantation using current protocols., Methods: From January 2003 to August 2009, 593 lung transplants were performed at our institution. We compared 87 patients (14.7%) who received lungs from donors aged 55 years or older with 506 patients who received lungs from donors less than 55 years old. We also examined risk factors for mortality in recipients of lungs from older donors., Results: The incidence of major complications including severe primary graft dysfunction and early mortality rates were similar between the groups. However, posttransplant peak FEV1 was lower in the patients who received lungs from older donors (71.7% vs. 80.7%, P<0.05). In multivariate analysis, recipient pulmonary hypertension (transpulmonary pressure gradient >20 mm Hg) and prolonged intraoperative cardiopulmonary bypass were significant risk factors for mortality in the recipients of lungs from older donors., Conclusions: This large, single-center experience demonstrated that transplanting lungs from donors older than 55 years did not yield worse short- or long-term outcomes as compared with transplanting lungs from younger donors. However, transplanting lungs from older donors into recipients with pulmonary hypertension or recipients who required prolonged cardiopulmonary bypass increased the risk for mortality. Although lungs from older donors should not be excluded because of donor age alone, surgeons should carefully consider their patient selection criteria and surgical plans when transplanting lungs from older donors.

Background: Delayed chest closure (DCC) after lung transplantation is a viable option to be taken in the cases of prolonged cardiopulmonary bypass time, prolonged ischemic time, coagulopathic problems or oversized donor lung grafts. Decision-making for DCC in the operating room remains challenging to surgeons, because the impact of DCC on outcomes after lung transplantation has not yet been fully elucidated., Methods: We performed a retrospective review of 90 lung transplantations with DCC and 783 cases with primary chest closure to clarify the reasons for DCC, complications of DCC, and the risk factors for adverse outcomes., Results: The 30- and 90-day mortality in the DCC group was 7.8% and 9.9%, respectively. Early post-operative bleeding and severe primary graft dysfunction (PGD) were higher in the DCC group (p<0.05). In multivariate analysis, prolonged cardiopulmonary bypass use (>4 hours), post-operative extracorporeal oxygen requirement and use of a DCC technique with open skin and retracted ribs were significantly associated with mortality (p<0.05), whereas prolonged duration of DCC was not. In a matched cohort study to compare the results of a DCC technique with skin closure to similarly matched controls with primary closure, DCC contributed to significantly decreased incidence of severe PGD (9.6% vs. 26%, p<0.05), leading to an improved post-transplant survival and functional status as compared with primary closure., Conclusions: Our technical approaches to prevent possible problems in DCC cases are described. DCC can be safely performed with acceptable procedure-related risks. DCC should not be considered a sub-optimal option after lung transplantation., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Individual ventricular assist device (VAD) design may affect leukocytes and impact immunity. Few studies have presented leukocyte and infection profiles in VAD patients over the course of the implant period. CD11b (MAC-1) expression on granulocytes is an indicator of activation during inflammation, mediating extravasation and the release of reactive oxygen species in tissue. No reported studies have presented MAC-1 expression on circulating granulocytes in VAD patients. Fifty-six patients implanted at a single center with a HeartMate II (HMII; n = 32), HeartWare (HW; n = 12), or Thoratec pneumatic VAD (PVAD; n = 12) between 1999 and 2011 were followed for 120 days of support. The leukocyte profiles and infectious events of all patients were evaluated; additionally, a subset had MAC-1 expression on circulating granulocytes was measured (HMII n = 9; HW n = 7; PVAD n = 4). All groups exhibited a significant peak in leukocyte numbers at postoperative day (POD) 14 while simultaneously experiencing a significant decrease in hematocrit. HMII patients exhibited a 3.2-fold increase in granulocyte MAC-1 expression at POD 14, and the temporal trend over the implant period differed from that experienced by HW patients. Further, HW patients experienced significantly fewer infection events. Alterations in leukocyte profiles and granulocyte activation experienced by VAD patients appear to be device-specific. Elevations in leukocyte activation may be related to an increased risk for infection, although the specific relationship between these phenomena in this patient group is not known., (Copyright © 2013 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

A simple technique for reconstructing a short recipient left atrial cuff during lung transplantation is described. After opening the confluence of the pulmonary veins, the cut ends of the pulmonary veins are sutured together, posteriorly and anteriorly. This effectively lengthens the cuff allowing safe left atrial anastomosis. This technique has been applied in 3 patients with no technique-related complications., (© The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP., Methods: The donor heart-lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4 °C. And then, the heart-lung blocks were flushed retrogradely and warmed up to 37 °C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2, 8% CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37 °C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR)., Results: R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation., Conclusions: Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.

Background: Continuous flow (CF) left ventricular assist devices (LVAD) are afterload sensitive and therefore pump performance is affected by hypertension. In addition, poorly controlled hypertension may increase the risk of aortic insufficiency (AI) and stroke. Blood pressure regimens after CF LVAD have not been studied and their impact on rates of AI and stroke are unknown., Methods: Patients who had CF LVAD at a single center and were supported greater than 30 days were included. Blood pressure was monitored at home by Doppler. Outpatient management of blood pressure was conducted according to a predefined institutional protocol (target mean arterial pressure ≤ 80 mm Hg)., Results: A total of 96 patients were included. At the end of follow-up, 25 patients were not on an antihypertensive drug, of these 9 died. Of the 74% receiving antihypertensives, 54% required 1 medication, 34% were on 2, 10% were on 3, and 3% were on 4 or more. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (85% of patients on an antihypertensive) and beta blockers (30%) were the most commonly prescribed medications. There was a significantly higher neurologic event rate in those on no antihypertensives compared with those on antihypertensives (p = 0.009). Only 3% of patients with no or mild AI at baseline progressed to develop moderate or greater AI after a mean of 201 days of follow-up., Conclusions: Blood pressure control can be achieved in patients with CF LVADs, with the majority of patients requiring only 1 or 2 antihypertensives., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for ≥6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log10 copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity.

Objectives: Cardiovascular complications are a major cause of morbidity and mortality among renal transplant recipients. This study assessed perioperative risk factors for mortality and long-term outcomes in renal transplant recipients who underwent cardiac surgery., Methods: From 1999 to 2010, 92 renal transplant recipients with a functioning allograft underwent cardiac surgery at our institution. Cardiac procedures included coronary artery bypass grafting (43 patients, 46%), isolated valve surgery (17 patients, 18%), combined coronary artery bypass grafting and valve surgery (18 patients, 19%), and aortic procedures (7 patients, 7%)., Results: Transient renal failure requiring dialysis occurred in 20 of 92 patients (21%), with 3 not recovering renal function and returning to a permanent dialysis regimen while in the hospital. After cardiac surgery 30-day, 1-year, 5-year, and 8-year survival rates were 89%, 72%, 47%, and 30%, respectively. Freedom from dialysis was 90% after 1 year, 66% after 5 years, and 49% after 8 years. Risk factors for 30-day mortality were age > 65 years, left ventricle ejection fraction < 35%, and a combined cardiac procedure. Pulmonary hypertension and diabetes were risk factors for death from a cardiac cause after discharge. Diabetes, dyslipidemia, preoperative use of an intra-aortic balloon pump, postoperative creatinine > 2 mg/dL, and transient renal failure requiring dialysis were associated with a permanent dialysis requirement after cardiac surgery., Conclusions: Cardiac surgery in patients receiving renal transplant who have functioning allograft has acceptable outcomes. If combined procedures are required, patients should be carefully considered. Transient postoperative renal impairment, even if resolved at discharge, increases the risk for allograft failure during long-term follow-up., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Airway fire is a well-documented event during airway surgery with devastating outcomes. Individuals involved in the care of these patients should be aware of this possible complication and precautions needed to prevent this complication.

Repopulation of memory T cells (Tmem) in allograft recipients after lymphodepletion is a major barrier to transplant tolerance induction. Ineffective depletion of naïve T cells (Tn) and Tmem may predispose to repopulation of Tmem after transplantation. Cynomolgus macaque monkeys given heart allografts were lymphodepleted using Alemtuzumab (Campath-1H; anti-CD52). Peripheral blood (PB) and lymph nodes (LN) were analyzed for CD95(-) (Tn) and CD95(+) cells (Tmem), one day, one month and up to three months after Alemtuzumab infusion. CD52 expression, susceptibility to Alemtuzumab cytotoxicity and pro-apoptotic caspase-3 were evaluated in Tn and Tmem. In vivo, Alemtuzumab induction profoundly depleted lymphocytes in PB (99% reduction) but exerted a lesser effect in LN (70% reduction), with similar depletion of Tn and Tmem subsets. After transplantation, Tmem comprised the majority of lymphocytes in PB and LN. In vitro, LN T cells were more resistant to Alemtuzumab-mediated cytotoxicity than PB lymphocytes. CD4(+) Tn and Tmem were equally susceptible to Alemtuzumab-mediated cytotoxicity, whereas CD8(+) Tn were more resistant than CD8(+) Tmem. However, no significant differences in CD52 expression between lymphocyte subsets in PB and LN were observed. Caspase-3 expression was higher in PB than LN T cells. CD4(+) and CD8(+) Tn expressed lower levels of Caspase-3 than Tmem, in both PB and LN. Thus, after Alemtuzumab infusion, residual Tn in secondary lymphoid tissue may predispose to rapid recovery of Tmem in allograft recipients., (© 2013.)

Objectives: A sternal-sparing approach for bilateral lung transplantation was recently applied to reoperative lung transplant cases and is compared with the traditional clamshell approach., Methods: A retrospective analysis of 15 consecutive reoperative bilateral lung transplants performed from January 2008 to April 2011 was conducted. Outcomes were compared between the first 11 patients who underwent the traditional clamshell and the most recent 4 patients who underwent the sternal-sparing approach., Results: The indication for retransplantation was obliterative bronchiolitis in all patients. Both groups were similar with regard to age, allograft ischaemic time and operative time. Cardiopulmonary bypass was more frequent in the sternal-sparing group although required for a shorter period of time. The need for postoperative extracorporeal membrane oxygenation for primary graft dysfunction was similar in both groups. The length of ICU care and total hospitalization length of stay were similar for the sternal-sparing group compared with the traditional clamshell approach. Operative mortality and overall survival also did not differ., Conclusions: Reoperative bilateral lung transplantation with a sternal-sparing approach is feasible and may yield outcomes similar to those in the traditional clamshell approach. Further analysis with larger numbers of patients is warranted to delineate the benefits of this approach for patients requiring reoperative lung transplantation.

Background: Lung volume reduction surgery (LVRS) as a bridge to lung transplantation was first advocated in 1995 and published studies have supported the concept but with limited data. The risk-benefit tradeoffs of the combined procedure have not been thoroughly examined, although substantial information regarding LVRS has emerged., Methods: Of 177 patients who underwent lung transplantation for end-stage emphysema between 2002 and 2009 at our center, 25 had prior LVRS (22 bilateral and 3 unilateral). Lung transplantation was performed 22.9±15.9 months after LVRS. We compared in-hospital morbidity, functional capacity, and long-term outcomes of patients who underwent LVRS before lung transplantation with a matched cohort of patients without prior LVRS to assess the influence of LVRS on posttransplantation morbidity and mortality., Results: The incidence of postoperative bleeding requiring reexploration and the incidence of renal dysfunction requiring dialysis were higher in patients with LVRS before lung transplantation. Posttransplantation peak forced expiratory volume in 1 s was worse in patients with LVRS before lung transplantation (56.7% vs. 78.8%; P<0.05). Five-year survival was not significantly different (59.7% in patients with LVRS before lung transplantation vs. 66.2% in patients with lung transplantation alone). In multivariate analysis, age more than 65 years, prolonged cardiopulmonary bypass time, and severe pulmonary hypertension were significant predictors for mortality (P<0.05)., Conclusions: Although LVRS remains a viable option as a bridge to lung transplantation in appropriately selected patients, LVRS before lung transplantation can impart substantial morbidity and compromised functional capacity after lung transplantation. LVRS should not be easily considered as a bridge to transplantation for all lung transplant candidates.