Incidence Of Primary Graft Dysfunction Research Articles

Abstract 11945: Improved Outcomes in Severe Primary Graft Dysfunction Following Heart Transplantation With Donation After Circulatory Death Compared to Donation After Brain Death

Introduction: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplant, is more common following heart donation after circulatory death (DCD) than following donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity, and outcomes of patients experiencing PGD after DCD compared to DBD heart transplant. Methods: We reviewed the medical records of all adult heart transplant recipients at our institution between March 2016 and December 2021. Patients undergoing multi-organ transplant were excluded. PGD was diagnosed within 24 hours after transplant according to modified ISHLT criteria and was classified by severity and ventricles involved. Results: A total of 459 qualifying patients underwent heart transplant during the study period, of whom 65 (14%) were DCD recipients and 394 (86%) were DBD recipients. The incidence of PGD in DCD and DBD recipients was 34% and 23%, respectively (p = 0.070). DCD recipients were more likely to experience severe, biventricular PGD than DBD recipients (19% vs. 7.3%, p = 0.004). Among patients with severe PGD, DCD recipients experienced shorter duration of mechanical circulatory support (ECMO, VAD, or balloon pump; mean 6.0 ± 2.5 vs. 12.1 ± 11.3 days, p = 0.039; Figure), shorter post-transplant hospital length of stay (32.4 ± 41.1 vs. 61.9 ± 47.7 days, p = 0.004), and a trend toward improved 60-day survival (100% vs. 80%, p = 0.170) and one-year survival (92% [95% CI: 76%-100%] vs. 69% [53%-84%]). Conclusions: DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, short- and medium-term outcomes among patients with severe PGD were improved in DCD compared to DBD recipients. These data suggest different mechanisms of graft dysfunction and recovery following DCD compared to DBD and support the expansion of the heart donor pool with DCD in most potential recipients.

IL-1β-dependent extravasation of preexisting lung-restricted autoantibodies during lung transplantation activates complement and mediates primary graft dysfunction.

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1β–mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.

Aquaporin-1 inhibition exacerbates ischemia-reperfusion-induced lung injury in mouse

BackgroundIschemia-reperfusion injury (IRI), which involves severe inflammation and edema, is an inevitable feature of the lung transplantation process and leads to primary graft dysfunction (PGD). The activation of aquaporin 1 (AQP1) modulates fluid transport in the alveolar space. The current study investigated the role of AQP1 in ischemia-reperfusion (IR)-induced lung injury. MethodsA mouse model of lung IR was established by clamping the left lung hilar for 1 h and released for reperfusion for 24 h. The AQP1 inhibitor acetazolamide (AZA) was administered 3 days before lung ischemia with a dose of 100 mg/kg per day via gavage. Lung injury was evaluated using the ratio of wet-to-dry weight, peripheral bronchial epithelial thickness, degree of angioedema, acute lung injury score, neutrophil infiltration, and cytokine concentrations in bronchoalveolar lavage fluid. ResultsCompared with sham treatment, ischemia with no reperfusion (IR 0h) and ischemia with reperfusion for 24 h (IR 24 h) significantly upregulated AQP1 expression, increased the wet/dry weight ratio, angioedema, neutrophil infiltration and cytokine production (interleukin -6 and tumor necrosis factor -α) and thickened the peripheral bronchial epithelium. AZA exacerbated inflammation and pulmonary edema. ConclusionAQP1 may exert a protective effect against IR-induced lung injury, which could be attributed to alleviating pulmonary edema and inflammation. AQP1 upregulation might be a potential application to alleviate lung IRI and decrease the incidence of PGD.

315.5: Mesenchymal Stromal Cell Therapy as Promising Option To Increase Organ Availability and Reduce Graft Failure

Introduction: Lung transplantation (LTx) is an established therapeutic option for end-stage pulmonary disease. However, waiting lists are long and the treatments remains hampered by donor lung scarcity accompanied with high early and late mortality rates. Novel treatment options to regenerate marginal donor lungs turned down for transplant are needed to combat both waiting list mortality and post-operative complications such as primary graft dysfunction (PGD). Although donor numbers increase, donor organ utility is low due to acute lung injury (ALI) which can be induced by gastric aspiration. Mesenchymal stromal cells (MSCs) have caught attention for organ regeneration as they display an array of potentially beneficial effects: they are known to be immunomodulatory, antifibrotic and microbiocidal. MSCs have demonstrated tissue regenerative capacities as documented in preclinical studies, e.g., improved function of diseased lungs. Aim: The aim of the current study is to evaluate the effect of MSCs administered to aspiration damaged lungs during ex vivo lung perfusion (EVLP) and to recipients post transplantation with a focus on their capacity to improve damaged lungs and to decrease the incidence of PGD at 72h post transplantation. Materials and Methods: Lung injury was induced in 12 donor pigs using gastric content with a pH of 2. The donor-recipient pairs were randomized to receive MSCs or placebo treatment during the beginning of EVLP and post LTx. Lungs were treated with EVLP for 4 hours followed by a left lung transplantation. The recipient was kept under anesthesia and closely monitored for three days post LTx. In the final phase of the experimental setup an isolated assessment of the transplanted lung was achieved following a right pneumonectomy. Treatment effects were assessed by clinically relevant parameters, including PaO2/FiO2 ratio, pulmonary vascular resistance (PVR), and lactate, further by histopathological changes, immune cell counts in peripheral blood and cytokine and chemokine levels in plasma and bronchoalveolar lavage fluid during the course of the experiment. Results: The lung functionality as evaluated by the PaO2/FiO2 ratios showed significantly increased lung function in treated recipients compared to both the non-treated recipients and to all lungs at the time of confirmed ALI. A tendency of higher PVR was seen among the non-treated recipients however, not significantly. Lactate was unchanged in both groups. Lung injury scores were also reduced in the treated group as compared to the non-treated group and to the lungs after lung injury was induced. On the third day of follow-up of the recipients, all recipients in the treatment group had PGD grade 0, while the non-treated group consisted of one recipient with grade 0, three with grade 2 and two with grade 3. Conclusion: MSC treatment emerges as a promising therapeutic option for restoring injured donor lungs for reacceptance into the donor pool and decreasing the incidence of PGD.

Lung Transplantation for COVID-19-related Lung Disease: Clinical Experience and Call for a Global Registry.

Lung Transplantation for COVID-19-related Lung Disease: Clinical Experience and Call for a Global Registry.

Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation

Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.

Longitudinal assessment of renal function after lung transplantation for cystic fibrosis: transition from post-operative acute kidney injury to acute kidney disease and chronic kidney failure

IntroductionThe clinical trajectory of post-operative acute kidney injury (AKI) following lung transplantation for cystic fibrosis is unknown.MethodsIncidence and risk factors for post-operative AKI, acute kidney disease (AKD) and chronic kidney disease (CKD) were retrospectively analyzed in cystic fibrosis patients undergoing lung transplantation. Logistic regressions, Chi-square, Cuzick rank tests, and Cox-proportional hazard models were used.ResultsEighty-three patients were included. Creatinine peaked 3[2–4] days after transplantation, with 15(18%), 15(18%), and 20(24%) patients having post-operative AKI stages 1, 2, and 3, while 15(18%), 19(23%) and 10(12%) developed AKD stage 1, stage 2 and 3, respectively. Higher AKI stage was associated with worsening AKD (p = 0.009) and CKD (p = 0.015) stages. Of the 50 patients with AKI, 32(66%) transitioned to AKD stage > 0, and then 27 (56%) to CKD stage > 1. Female sex, extracorporeal membrane oxygenation support as a bridge to lung transplant and at the end of the surgery, the use of intraoperative blood components, and cold-ischemia time were associated with increased risk of post-operative AKI and AKD. Higher AKI stage prolonged invasive mechanical ventilation (p = 0.0001), ICU stay (p = 0.0001), and hospital stay (p = 0.0001), and increased the incidence of primary graft dysfunction (p = 0.035). Both AKI and AKD stages > 2 worsened long-term survival with risk ratios of 3.71 (1.34–10.2), p = 0.0131 and 2.65(1.02–6.87), p = 0.0443, respectively.DiscussionAKI is frequent in cystic fibrosis patients undergoing lung transplantation, it often evolves to AKD and to chronic kidney disease, thereby worsening short- and long-term outcomes.Graphical abstract

Extracorporeal membrane oxygenation support for lung transplantation: Initial experience in a single center in China and a literature review.

BackgroundExtracorporeal membrane oxygenation (ECMO) is a versatile tool associated with favorable outcomes in the field of lung transplantation (LTx). Here, the clinical outcomes and complications of patients who underwent LTx with ECMO support, mainly prophylactically both intraoperatively and post-operatively, in a single center in China are reviewed.MethodsThe study cohort included all consecutive patients who underwent LTx between January 2020 and January 2022. Demographics and LTx data were retrospectively reviewed. Perioperative results, including complications and survival outcomes, were assessed.ResultsOf 86 patients included in the study, 32 received ECMO support, including 21 who received prophylactic intraoperative use of ECMO with or without prolonged post-operative use (pro-ECMO group), while the remaining 54 (62.8%) received no external support (non-ECMO group). There were no significant differences in the incidence of grade 3 primary graft dysfunction (PGD), short-term survival, or perioperative outcomes and complications between the non-ECMO and pro-ECMO groups. However, the estimated 1- and 2-year survival were superior in the pro-ECMO group, although this difference was not statistically significant (64.1% vs. 82.4%, log-rank P = 0.152; 46.5% vs. 72.1%, log-rank P = 0.182, respectively). After regrouping based on the reason for ECMO support, 30-day survival was satisfactory, while 90-day survival was poor in patients who received ECMO as a bridge to transplantation. However, prophylactic intraoperative use of ECMO and post-operative ECMO prolongation demonstrated promising survival and acceptable complication rates. In particular, patients who initially received venovenous (VV) ECMO intraoperatively with the same configuration post-operatively achieved excellent outcomes. The use of ECMO to salvage a graft affected by severe PGD also achieved acceptable survival in the rescue group.ConclusionsProphylactic intraoperative ECMO support and post-operative ECMO prolongation demonstrated promising survival outcomes and acceptable complications in LTx patients. Particularly, VV ECMO provided safe and effective support intraoperatively and prophylactic prolongation reduced the incidence of PGD in selected patients. However, since this study was conducted in a relatively low-volume transplant center, further studies are needed to validate the results.

Is the Organ Care System (OCS) Still the First Choice With Emerging New Strategies for Donation After Circulatory Death (DCD) in Heart Transplant?

The scarcity of donor hearts continues to be a challenge in transplants for advanced heart failure patients. With an increasing number of patients on the waiting list for a heart transplant, the discrepancy in the number between donors and recipients is gradually increasing and poses a new challenge that plagues the healthcare systems when it comes to the heart. Several technologies have been developed to expand the donor pool in recent years. One such method is the organ care system (OCS). The standard method of organ preservation is the static cold storage (SCS) method which allows up to four hours of safe preservation of the heart. However, beyond four hours of cold ischemia, the incidence of primary graft dysfunction increases significantly. OCS keeps the heart perfused close to the physiological state beyond the four hours with superior results, which allows us to travel further and longer distances, leading to expansion in the donor pool. In this review, we discuss the OCS system, its advantages, and shortcomings.

Pretransplant physical frailty, postoperative delirium, and short-term outcomes among older lung transplant recipients.

Delirium is a common, complex medical challenge that faces surgical patients in the postoperative period. Patients undergoing lung transplantation are at especially high risk given their predisposition to physical frailty and prolonged hospitalization. We sought to investigate the relationship between physical frailty, delirium, and short-term lung transplantation outcomes. A retrospective study of adult patients who underwent lung transplantation was conducted. Pretransplant frailty markers, including the six-minute walk distance (6MWD) and short physical performance battery (SPPB), and postoperative outcomes, including the incidence of primary graft dysfunction (PGD) and the number of hospital free days alive in the 90-day interval following lung transplantation, were evaluated for association with delirium. A total of 100 patients were included, 38% of whom experienced delirium. Greater pretransplant SPPB scores (indicating lower physical frailty) associated with a lower incidence of postoperative delirium. Postoperative delirium also associated with the number of hospital free days alive, independent of PGD. Pretransplant frailty is associated with greater incidence of postoperative delirium, which associated with fewer days alive outside of the hospital. Targeting frailty and postoperative delirium may be modifiable risk factors to improve short-term clinical outcomes.

Sensitization is Independently Associated with Increased Risk of Primary Graft Dysfunction After Heart Transplantation

<h3>Purpose</h3> Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). We sought to determine the association between pre-transplant calculated panel reactive antibody (cPRA) value and the incidence of PGD while controlling for other known risk factors. <h3>Methods</h3> Consecutive adult HT recipients (n=672) from 1/2015 to 12/2019 at two high-volume centers were included. Definition and severity PGD were based on the 2014 ISHLT consensus statement. Peak cPRA values were collected for each patient prior to HT and high cPRA was defined as >50%. The primary outcome was the incidence of all PGD. Multi-variable logistic regression model was used to identify risk factors for PGD. <h3>Results</h3> The cohort was predominantly male (72.3%), with a mean age of 54.3±12.1 years and 23.1% had a durable left ventricular assist device as a bridge to HT. There were 150 (22.3%) cases of all PGD. Severe PGD occurred in 44 (6.6%) and mild-moderate PGD occurred in 106 (15.8%) patients. A total of 105 (15.6%) patients had high cPRA prior to HT. Univariable model identified PGD risk factors including ischemic time greater than 4 hours, pre-HT angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with and without neprilysin inhibitor use, donor and recipient age, and predicted heart mass ratio <0.86. Multivariable modeling showed that high cPRA was associated with increased incidence of all PGD (OR 1.72, 95% CI 1.07-2.76, p=0.025) when adjusted for co-variates (Table 1). Patients with no cPRA (0%) had significantly lower incidence of severe PGD compared to those with any detectable cPRA (>0%) (4.78 vs. 10.2%, p=0.018). <h3>Conclusion</h3> Patients with high pre-HT cPRA is associated with increased incidence of PGD, after adjustment for donor and recipient characteristics.

Outcomes of Mechanical Circulatory Support for Severe Primary Graft Dysfunction After DBD versus DCD Heart Transplantation

<h3>Purpose</h3> Severe primary graft dysfunction (PGD) is defined by need for mechanical circulatory support (MCS) after heart transplantation. Severe PGD is associated with increased short-term mortality but reported outcomes vary widely. The mechanism of PGD may differ for hearts donated after brainstem-determined death (DBD) and circulatory-determined death (DCD). The purpose of this study was to determine whether there are differences in PGD outcomes between DBD and DCD heart transplants. <h3>Methods</h3> We undertook a retrospective, observational study of all heart transplants performed at our institution since the onset of the DCD heart transplant programme (May 2015 to June 2021). Baseline donor and recipient characteristics were recorded. Outcome measures included duration of MCS, length of intensive care (ICU) stay, total length of hospital stay (LOS) and 90-day mortality. <h3>Results</h3> 280 heart transplants were performed during the study period, including 192 DBD and 88 DCD heart transplants. The overall incidence of severe PGD was 11.8% (n=33). These patients were initially supported with VA ECMO (n=28, 84.9%) or CentriMag RVAD (n=5, 15.1%), of which 6 patients (18.2%) were later converted from ECMO to CentriMag RVAD/BiVAD. The incidence of PGD was similar for DBD (n=21, 10.9%) and DCD (n=12, 13.6%) heart transplants (p=0.541). There were no significant differences in baseline characteristics between DBD and DCD groups. There were no significant differences in outcomes between DBD and DCD groups, including median duration (in days) of MCS (5 vs 6, p=0.679), ICU stay (22 vs 20.5, p=0.881) or total LOS (46 vs 48.5, p=0.454). 90-day mortality was 57.1% in the DBD group and 33.3% in the DCD group (p=0.188). <h3>Conclusion</h3> In one of the world's largest cohorts of DCD heart transplantation, we have not seen a significant difference in PGD incidence or outcomes between DBD and DCD heart transplant patients. The potential lower 90-day mortality in the DCD group may suggest that the natural history of PGD after DCD heart transplantation is more favourable compared with PGD seen after DBD heart transplantation.

Validation of a Simple to Use PGD Prediction Algorithm

<h3>Purpose</h3> Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. We previously developed an easy to use PGD predictive model utilizing the Lung Transplant Outcomes Group (LTOG) cohort. We therefore sought to demonstrate the net benefit of the model at an external site as a measure of model generalizability. <h3>Methods</h3> We tested external validation in a well-phenotyped lung transplant cohort from Washington University in St. Louis (WashU) for a PGD predictive model based on lung allocation score, body mass index, pulmonary arterial pressure, recipient total lung capacity, donor and recipient age and gender, donor mode of death, and donor distance to transplant center. We primarily employed decision curve analysis (DCA) to quantify the net benefit of the predictive model and also assessed model discrimination using the c-statistic and calibration using the Hosmer-Lemeshow (H-L) test. <h3>Results</h3> The incidence of PGD at WashU was lower than in the LTOG cohort (7% vs 25%); the validation model accounts for the differences in PGD incidence. The model demonstrated good discrimination (c-statistic=0.67) and calibration (H-L p=0.2, where non-significant p-value is good calibration). DCA describes whether the model performs better than alternatives of classifying everyone (or no one) as high PGD risk as well as the net benefit of the model across a range of decision thresholds. The DCA (Figure 1) shows that the predictive model demonstrates significant net benefit in the PGD incidence range 2-15%, incorporating the PGD incidence seen in the WashU cohort. <h3>Conclusion</h3> Our simple to implement PGD predictive model demonstrates excellent net benefit, even at centers with differing PGD incidence than the discovery cohort centers. This model can be used to identify recipients at high and low risk for PGD across a range of transplant centers, allowing treatment teams to be prepared for post-transplant complications and identify patients for potential enrollment in targeted intervention studies based on patient risk.

Keep Your Cool! One Year Outcomes with Use of a Hypothermic Preservation System Compared to Standard Storage with Ice During Heart Procurement

<h3>Purpose</h3> Traditionally, after procurement, donor hearts are cooled with ice during transport to the transplant center. However, this can lead to uneven cooling and can result in tissue injury, which may affect subsequent allograft function. The utilization of a hypothermic preservation system (SherpaPak, Paragonix) results in controlled and uniform cooling. This approach may enable longer-distance procurements and may result in better allograft function after transplant. <h3>Methods</h3> A single center study of heart transplantation using donor hearts transported on ice from 1/1/19-07/16/20 compared to a hypothermic preservation system (Sherpa) from 7/17/20-6/13/21. Patients were assessed for primary graft dysfunction (PGD), defined as requiring any mechanical circulatory support, length of stay (LOS) after transplant, graft function and one year survival. <h3>Results</h3> There were a total of 115 patients, 56 (49%) transported with Ice and 59 (51%) with Sherpa. There were no differences in recipient's baseline demographics: mean age (54 years), male (79%), and nonischemic (61%), but a higher use of LVAD in the Ice v Sherpa (18% v. 5%, p=0.03). Donor characteristics were similar: age (35 years), male (68%), white (59%), and cause of death (anoxia 38%, head trauma 41%, stroke 17%). The median post-transplant LOS was 20 days and not different between groups. Despite a longer ischemic time for the Sherpa v Ice transport (255 v. 230 minutes, p=0.021), there were no differences in incidence of PGD (17% v. 14%, p=0.69); median ejection fraction at 6 months (61%) and 12 months (61%); and 1 year patient survival (91% v. 95%, p=0.45), Figure 1a/b. <h3>Conclusion</h3> The use of a hypothermic preservation system results in similar one year patient survival and graft function, incidence of PGD, and hospital LOS, despite longer ischemic times. Use of this system safely enables more distant donor heart procurement.

Early Single Center Experience of Heart Transplantation from Donation After Circulatory Death Donors in the United States

<h3>Purpose</h3> Heart transplantation (HT) from donation after circulatory death (DCD) donors has been proposed as a means of addressing the scarcity of available donor grafts. International experience has suggested that DCD HT is safe, with outcomes comparable to donation after brain death (DBD) HT. Herein we describe our center's early experience using 2 DCD heart procurement strategies: 1) A direct procurement and perfusion (DPP) protocol, and 2) A thoracoabdominal normothermic regional perfusion (TA-NRP) protocol. <h3>Methods</h3> In September 2020, we launched a DCD HT program as part of a randomized trial using DPP and the OCS Transmedics platform. We subsequently launched a TA-NRP program. The TA-NRP protocol uses mobile cardiopulmonary bypass (CPB) to assess hearts in situ following declaration of death. Functional warm ischemic time (FWIT) was defined as the time from onset of mean pressure <50mm Hg or oxygen saturation <70%, to cold flush (DPP) or initiation of CPB (TA-NRP). FWIT was ≤30 minutes for DPP, while there was no pre-defined limit for TA-NRP. Data was prospectively collected. Donor and recipient characteristics were analyzed. We report 30-day survival as the primary endpoint. Secondary endpoints include incidence of primary graft dysfunction requiring mechanical support, immediate cardiac performance, ventilator days, need for renal replacement therapy, and intensive care and hospital length of stay. <h3>Results</h3> From September 2020 to October 2021, our center attended 50 candidate DCD donors, and performed 33 DCD HTs (66.0%), comprised of 13 DPP and 20 TA-NRP protocol donors. Among candidate DPP donors, 13 of 23 (56.5%) hearts were transplanted, whereas among candidate TA-NRP donors, 20 of 27 (74.1%) were transplanted. Year-to-date, DCD as a proportion of all HTs at our center has been 43.1%. Comparing similar time periods before and after implementing our DCD heart transplant program revealed a 20.3% increase in transplant activity. Donor and recipient characteristics are described in tabular format. 30-day survival is 100% among all DCD heart recipients. The incidence of primary graft dysfunction and other secondary endpoints are comparable with standard DBD HT. <h3>Conclusion</h3> DCD HT using both the DPP and TA-NRP procurement protocols is feasible and safe. Outcomes in our early single center experience are comparable with standard DBD HT.

Primary Graft Dysfunction (PGD) After Lung Transplantation in the UK: Incidence, Risk Factors and Patient Outcome

<h3>Purpose</h3> Primary graft dysfunction (PGD) is an important cause of morbidity and mortality after lung transplantation. Data for the diagnosis and grading of PGD are not routinely collected in the UK Transplant Registry (UKTR). We aimed to study the incidence and significance of PGD after lung transplantation in the United Kingdom (UK). <h3>Methods</h3> Data prospectively collected in the UKTR for all first-time adult lung transplants between 1 January 2010 and 31 December 2019 were reviewed, with analysis of retrospective data collected for the diagnosis and grading of PGD. Unadjusted 90-day, 1-year and 5-year survival by PGD grade was assessed using Kaplan Meier survival analysis and log-rank tests. Univariable analysis of recipients with or without PGD grade 3 at 72 hours post-transplantation, was performed. <h3>Results</h3> A total of 1720 recipients were identified, with PGD grading available for 1637. The incidence of PGD grade 3 at 72 hours post-transplantation was 14% (233 recipients). There was a significant difference in survival at 90-days, 1-year and 5-years for recipients with Grade 3 PGD at 72 hours post-transplant (p=<0.0001). Recipients with grade 3 PGD at 72 hours has a significantly higher proportion of Donors after Circulatory Death (DCD) (p=0.03), older donors (median age 46 [IQR32-54] years versus 47 [IQR37-56] p=0.01), donors with a positive smoking history (555 (40%) versus 126 (54%) p=0.0001) and higher urgency recipients (22 (9%) urgent and super urgent recipients versus 79 (6%) P=0.003). <h3>Conclusion</h3> This is the first national study of PGD after lung transplantation in the UK, with our results indicating a comparable incidence of PGD grade 3 with the published literature and a significant difference in short and long-term for those recipients with grade 3 PGD at 72 hours post-transplant. Further analysis is required to identify risk factors predictive of grade 3 PGD in our population.

Primary Graft Dysfunction After Heart Transplantation: Incidence and Current Risk Factors

<h3>Purpose</h3> Primary graft dysfunction (PGD) is a leading cause of perioperative mortality in heart transplant (HT). Yet the impact of the current increased use of high-risk recipients and donors for HT on the incidence of PGD is unknown. <h3>Methods</h3> This is a retrospective single-center study of adult patients who underwent isolated heart or heart-kidney transplant from January 2018 to March 2020 to evaluate the incidence and patient characteristics associated with PGD, as defined by the International Society for Heart and Lung Transplantation consensus guidelines. Baseline characteristics and postoperative outcomes were compared between patients with no/mild PGD versus moderate/severe PGD. Multivariate logistic regression was used to determine independent predictors of PGD. <h3>Results</h3> One-hundred seventeen patients were evaluated: 105 (89.7%) had no/mild PGD and 12 (10.3%) had moderate/severe PGD. Patients with moderate/severe PGD were less likely to be bridged to transplant with temporary mechanical circulatory support (MCS) (8.3% versus 55.2%, p=0.002) and were more likely to receive undersized hearts (donor/recipient weight ratio 0.93±0.14 versus 1.12±0.26, p=0.008). Moderate/severe PGD patients had a higher postoperative median vasoactive inotropic score (24.97 versus 6.50, p<0.001) and only one moderate/severe PGD patient required postoperative extracorporeal membrane oxygenation (ECMO). By multivariate analysis, undersized donor (odds ratio [OR] 1.055; 95% confidence interval [CI] 1.003-1.127, p<0.001) was an independent predictor of PGD and pre-transplant temporary MCS was a negative predictor of PGD (OR 0.075; 95% CI 0.003-0.580, p=0.033). <h3>Conclusion</h3> In this experience with HT in high acuity recipients, the incidence of moderate/severe PGD is low and need for post-transplant ECMO is rare. Interestingly, these data suggest that use of pre-transplant temporary MCS may be protective against moderate/severe PGD, and further investigation of this approach is indicated.

The Complete Score for Comprehensive Evaluation of Donor Lungs in Ex-Vivo Lung Perfusion: An Approach for Optimizing the Outcomes of Transplantation

<h3>Purpose</h3> The imperfection of the currently utilized tools for assessing graft function in acellular ex-vivo lung perfusion (EVLP) has led our team to develop a comprehensive evaluation scoring system. This study aimed to validate this scoring system in our clinical EVLP program. <h3>Methods</h3> One hundred twelve EVLP cases were performed in our program since 2018. Data from the first 73 cases (derivation cohort) were retrospectively analyzed to identify the included evaluation parameters and to inform the cutoff values in the scoring system using Youden index. The scoring system was then prospectively applied in the remaining 39 cases (validation cohort). The comprehensive lung evaluation EVLP (COMPLETE) score included ultrasound evaluation, lung weight measurement, compliance, airway pressure, deflation, oxygenation, lactate level, bronchoscopy, and x-ray. <h3>Results</h3> Out of 112 EVLP cases, 75 (67%) were transplanted with 98.7% 30-day survival. The incidence of primary graft dysfunction (PGD) grades 0, 1, 2, and 3 at 72 hours post-transplant were 21, 63, 8, and 8 %, respectively. The COMPLETE score cutoff value for transplant suitability identified by the derivation cohort was 12 (AUC 1, 100% sensitivity & specificity) which was then applied in the validation cohort. Only two recipients in the validation cohort had PGD3 (which appeared to be related to intraoperative factors, not donor factors). The COMPLETE score had a significant correlation with IL-1β perfusate levels (r = 0.44, <i>p</i> < .001). Nine cases did not meet the standard criteria (FDA approved) for transplant suitability on EVLP but were transplanted based on their COMPLETE scores with 100% 30-day survival. Of those, 1 had PGD0, 7 had PGD1, and 1 had PGD3. On the other hand, 10 cases met the standard criteria for transplant suitability but were deemed non-suitable based on their COMPLETE scores and the post-EVLP pathological examination showed significant edema in 4 cases, acute lung injury in 4 cases, and pulmonary embolism in 2 cases. <h3>Conclusion</h3> Our novel COMPLETE scoring system provides a protocolized comprehensive evaluation of donor lungs on EVLP. It can be used to optimize the outcomes of lung transplantation by increasing utilization rates after EVLP and by identifying donor factors that might lead to unfavorable outcomes following transplantation.

Mechanical Circulatory Support During Lung Transplantation: Choices, Outcomes and Impact of Duration

<h3>Purpose</h3> Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) has recently replaced cardiopulmonary bypass (CPB) as the method of choice for mechanical circulatory support during lung transplantation (LTx). The aim of this study was to compare the outcomes of using ECMO versus CPB and examine the impact of its duration in a contemporary LTx cohort. <h3>Methods</h3> Between January 2017, and January 2020, 379 LTx were performed at our center. CPB was utilized in 111 and VA ECMO in 33 cases (unmatched cohort). After exclusion of patients who underwent concomitant cardiac procedures or retransplantation (all were in CPB group), the 33 VA ECMO patients were matched to CPB patients with a 1:2 ratio based on primary diagnosis, LTx type (bilateral or single), age, lung allocation score, body mass index, donor type (brain death or cardiac death), and duration of mechanical circulatory support. <h3>Results</h3> In the unmatched cohort, CPB group had a significantly higher incidence of re-exploration for bleeding and hospital mortality compared to ECMO group (15.3% vs 3.0%, <b>p = .047</b>; 10.8% vs 0%, <b>p = .038</b>, respectively). There were no statistically significant differences between CPB and ECMO groups in ICU stay, hospital stay, incidence of primary graft dysfunction (PGD) at 72 hours, postoperative tracheostomy, post-transplant ECMO use, re-admission, or 1-year survival. In the matched cohort, the differences between CPB and ECMO groups in both incidence of re-exploration for bleeding or hospital mortality were found to be statistically insignificant (13.6% vs 3.0%, <i>p</i> = .092; 7.6% vs 0%, <i>p</i> = .125, respectively). The differences between both groups in the other outcome endpoints remained insignificant. In the CPB group, patients with higher grades of PGD at 72 hours had significantly longer duration of CPB (PGD 0, 1, 2, 3 median 217, 209, 250, 289 minutes, <b>p = .014</b>, respectively). In the ECMO group, there were no differences in duration of ECMO between patients with different PGD grades. <h3>Conclusion</h3> Despite having a significantly higher incidence of re-exploration for bleeding and hospital mortality in CPB group in the unmatched cohort, there were no statistically significant differences between the two groups in the studied outcomes in the matched cohort, although there were strong trends. Notably, longer CPB time was associated with higher PGD grades whereas time on ECMO was not associated with PGD grades.

Normothermic Ex Vivo Lung Perfusion (Novel) as an Assessment of Extended Criteria Donor Lungs: A Prospective Multi-Center Clinical Trial

<h3>Purpose</h3> <i>Ex vivo</i> lung perfusion (EVLP) allows re-evaluation of extended criteria/marginal donor lungs. This can increase the number of lung transplants. However, the long-term outcomes of transplanting EVLP-screened lungs in a multicenter setting are unknown. We proposed to evaluate the short- and long-term outcomes of EVLP performed at multiple centers. <h3>Methods</h3> This is a prospective, nonrandomized clinical trial. Seventeen lung transplant centers in the United States. Adult patients with end-stage pulmonary disease requiring lung transplant from May 2011 to December 2017 were eligible. Lung allografts initially deemed extended criteria/marginal (n=216) were placed on EVLP and re-evaluated prior to transplant. Patients received either standard donors (n=116) or lungs screened with EVLP (n=110). <h3>Results</h3> Half of the lung grafts (110/216, 50.9%) placed on EVLP were transplanted. The incidence of primary graft dysfunction 24 hours post-transplant was higher in the EVLP group (25.5% vs 10.3%, <i>p</i>=0.003), but was not significantly different 48 hours (EVLP: 15.5%, control: 9.5%, <i>p</i>=0.49) and 72 hours (13.6% vs 6.9%, p=0.34) post-transplant. Survival was not significantly different between the 2 groups 1 year (n=226, EVLP: 86%, control: 94%, <i>p</i>=0.06), 3 years (n=226, EVLP: 68%, control: 76%, <i>p</i>=0.16, Figure), or 5 years (n=159, EVLP: 59%, control: 65%, <i>p</i>=0.68) post-transplant. There were also no differences in pulmonary function, the incidence of chronic lung allograft dysfunction or quality of life measures post-transplant. <h3>Conclusion</h3> In this multicenter study, recipients of lungs that were re-evaluated on EVLP and deemed suitable for transplant had similar outcomes as a recipients of a standard lung transplants. EVLP offers the opportunity to screen donated lungs initially considered high risk and can safely increase the availability of transplantable lungs without compromising outcomes.