Incidence Of Primary Graft Dysfunction Research Articles

Xenotransplantation of Mitochondria: A Novel Strategy to Alleviate Ischemia-Reperfusion Injury during Ex Vivo Lung Perfusion

Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce the incidence of PGD is mitochondrial transplantation. In this study, we explored the delivery of isolated mitochondria in 4 hour ex vivo lung perfusion (EVLP) before transplantation as a means to mitigate IRI. To provide a fresh and viable source of mitochondria, as well as to streamline the workflow without the need for donor muscle biopsies, we investigated the impact of autologous, allogeneic and xenogeneic mitochondrial transplantation. In the xenogeneic settings, isolated mitochondria from mouse liver were utilized while autologous and allogeneic sources came from pig skeletal muscle biopsies. Treatment with mitochondrial transplantation increased the P/F ratio and reduced pulmonary peak pressure of the lungs during EVLP, compared to lungs without any mitochondrial transplantation, indicating IRI mitigation. Extensive investigations using advanced light and scanning electron microscopy did not reveal evidence of acute rejection in any of the groups, indicating safe xenotransplantation of mitochondria. Future work is needed to further explore this novel therapy for combating IRI in lung transplantation, where xenotransplantation of mitochondria may serve as a fresh, viable source to reduce IRI.

Outcomes of controlled DCDD lung transplantation after thoraco-abdominal vs abdominal normothermic regional perfusion: The Spanish experience

ObjectiveThoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs. MethodsThis is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in two groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart versus abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, ICU and hospital length of stay, early survival rates, and mid-term outcomes. Results283 cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs. 7.6%; p=0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3%% vs. 41.5%; p=0.005). We found no significant differences between the groups regarding other post-transplant outcome variables. ConclusionsTA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.

Contrasting predictors of severe primary graft dysfunction following transplant for chronic and acute respiratory failure.

Lung transplantation represents a pivotal intervention for individuals grappling with end-stage lung diseases, and the role of lung transplantation in acute respiratory distress syndrome (ARDS) patients has garnered increased attention especially after the coronavirus disease 2019 (COVID-19) pandemic. Multiple studies have demonstrated a high incidence of primary graft dysfunction (PGD) in patients with ARDS compared to contemporaneous controls undergoing transplantation for chronic end-stage lung diseases although underlying mechanisms or risk factors remain unknown. This retrospective study investigates the contrasting risk factors for PGD grade 3 in patients with ARDS and chronic respiratory failure undergoing lung transplantation. The study included 293 patients who underwent lung transplantation from January 2018 through June 2023. We performed a multivariate logistic regression analysis using variables from the univariate logistic regression analyses to predict PGD grade 3. Our findings reveal distinct predictors for PGD grade 3 in the two cohorts. ARDS patients had higher incidence of PGD grade 3 than non-ARDS patients (30.2% vs. 9.6%, P<0.001). Multivariate logistic regression analysis showed ischemic time [odds ratio (OR) =0.60; 95% confidence interval (CI): 0.40-0.90; P=0.01] as predictor of PGD grade 3 for non-ARDS patients, and age (OR =0.72; 95% CI: 0.52-0.99; P=0.048), pre-operative albumin (OR <0.01; 95% CI: <0.01-0.74; P=0.042) for ARDS patients. Interestingly, there was no notable difference in post-transplant survival between the two groups. This study highlights differing risk profiles for severe PGD in ARDS and non-ARDS lung transplant recipients, underscoring the need for tailored approaches in managing these patients. It paves the way for further research to refine strategies aimed at reducing PGD incidence and enhancing transplant outcomes in these distinct populations.

Amniotic fluid-derived mesenchymal stem cells reduce inflammation and improve lung function following transplantation in a porcine model

BackgroundLung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes. MethodsIn a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion before transplantation. Treatment consisted of three doses of 2x106 cells/kg: one during ex vivo lung perfusion and two after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD). ResultsRepeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO2/FiO2 ratios and reduced incidence of PGD. ConclusionsRepeated injection of lung-specific cell treatment during EVLP and post-transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of post-operative outcomes.

Donor plasma VEGF-A as a biomarker for myocardial injury and primary graft dysfunction after heart transplantation

BackgroundVascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. MethodsWe examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into three equal-sized groups (low VEGF <500 ng/L, n=28; moderate VEGF 500-3000 ng/L, n=28; and high VEGF >3000 ng/L, n=27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for five years. ResultsBaseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. ConclusionsOur findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria.

Systemic Inflammation Differences in Brain-vs. Circulatory-Dead Donors: Impact on Lung Transplant Recipients.

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.

Does lung procurement and exposure to Perfadex impact heart transplantation outcomes.

Some studies have shown increased incidence of Primary Graft Dysfunction (PGD) after heart and lung procurement for heart transplant recipients. There have been limited investigations of the impact of lung procurement on heart procurement and the potential effects of the exposure to the type of lung preservation solution, the volume of the lung preservation solution and adequacy of decompression of the heart during heart and lung procurement and the impact on heart transplant outcomes. Adult heart transplant recipients in the UNOS database recorded from January 1, 2000 to June 30, 2022 formed the study cohort. Any heart that was procured with a lung team that utilized Perfadex preservation solution (XVIVO, Gothenburg, Sweden) was classified as exposed to Perfadex and otherwise classified as not exposed to Perfadex. Lung procurements performed with a preservation solution other than Perfadex or unknown were excluded (n=2486). Simple comparisons were made with t-tests or chi-squared tests. Logistic regression models were used to predict 30 day and 1 year survival. Accelerated failure time models were employed to analyze time to death and time to rejection. The cohort consisted of 34192 heart transplants, of which 21928 donors were not exposed to Perfadex (64.1%). There were statistically, but not clinically, significant differences in donor characteristics for these groups including in donor age (33.34±11.01 not exposed vs. 30.70±10.69 exposed; p<.001), diabetic donor (4% not exposed vs. 3% exposed; p=.004), and ischemic time (3.28±1.09h not exposed vs. 3.24±1.05h exposed; p=.002). In adjusted models, for all included donors, Perfadex exposure was associated with increased short term mortality, but no long term difference (1 year mortality OR 1.10, p=.014). Perfadex exposure was associated with increased short-term mortality for heart transplant recipients. Mechanistic investigation is warranted.

Single center study investigating the clinical association of donor-derived cell-free DNA with acute outcomes in lung transplantation.

Circulating donor-derived cell-free DNA (dd-cfDNA) levels have been proposed as a potential tool for the diagnosis of graft injury. In this study, we prospectively investigated dd-cfDNA plasma levels and their association with severe primary graft dysfunction (PGD) and graft rejection after lung transplant. A total of 40 subjects undergoing de-novo lung transplants at our institution were recruited in this study. Blood samples were collected at various time points before and after lung transplant for 1 year. Dd-cfDNA in samples was determined using AlloSure assay (CareDx Inc.). The correlation of the value of %dd-cfDNA was investigated with the incidence of PGD, acute cellular rejection (ACR), and donor-specific antibody. We observed a rapid increase of %dd-cfDNA in the blood of recipients after lung transplantation compared to baseline. The levels of dd-cfDNA decreased during the first two weeks. The peak was observed within 72 h after transplantation. The peak values of %dd-cfDNA varied among subjects and did not correlate with severe PGD incidence. We observed an association between levels of %dd-cfDNA from blood collected at the time of transbronchial biopsy and the histological diagnosis of ACR at 3 weeks. Our data show that circulating dd-cfDNA levels are associated with ACR early after transplantation but not with severe PGD. Plasma levels of dd-cfDNA may be a less invasive tool to estimate graft rejection after lung transplantation however larger studies are still necessary to better identify thresholds.

Prognosis of Lung Transplantation in Patients with Acute Exacerbations of Interstitial Lung Disease: A Meta-Analysis Based on Cohort Studies.

This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD). We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library, with the primary outcomes being overall survival (OS), acute cellular rejection (ACR), primary graft dysfunction (PGD), and length of stay (LOS). Five cohort studies were included in this meta-analysis, with 183 patients enrolled in the AE-ILD group and 337 patients in the stable-ILD group. The results showed that in regard to perioperative outcomes, the AE-ILD group did not differ from the stable-ILD group in the incidence of ACR (relative risks [RR] = 0.34, p = 0.44) and the incidence of PGD Ⅲ (RR = 0.53, p = 0.43), but had a longer LOS (mean difference = 9.15, p = 0.02). Regarding prognosis, the two also did not differ in 90-day OS (RR = 0.97, p = 0.59), 1-year OS (RR = 1.05, p = 0.66), and 3-year OS (RR = 0.91, p = 0.76). Our study concluded that the efficacy of lung transplantation in patients with AE-ILD is not inferior to that of patients with stable ILD. Lung transplantation is one of the potential treatments for patients with AE-ILD.

Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb): Protocol for a Multicenter Clinical Randomized Controlled Trial.

Lung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main factor in late mortality after LTx. PGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2). Increasing the PaO2/FiO2 ratio is thus critical and has an impact on survival. There is a general lack of effective treatments for PGD. When a transplanted lung is not accepted by the immune system in the recipient, a systemic inflammatory response starts where cytokines play a critical role in initiating, amplifying, and maintaining the inflammation leading to PGD. Cytokine filtration can remove these cytokines from the circulation, thus reducing inflammation. In a proof-of-concept preclinical porcine model of LTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study, we successfully treated patients undergoing LTx with cytokine filtration (ClinicalTrials.gov; NCT05242289). The purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving LTx outcome, based on its effects on oxygenation ratio, plasma levels of inflammatory markers, PGD incidence and severity, lung function, kidney function, survival, and quality of life compared with standard treatment with no cytokine filtration. This study is a Swedish national interventional randomized controlled trial involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with LTx. Specifically, this study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a LTx procedure, can lead to improved patient outcomes. This study seeks to assess various aspects of patient recovery and overall health to ascertain the potential positive impact of this intervention on the posttransplantation course. The process of patient recruitment for this study is scheduled to commence subsequent to a site initiation visit, which was slated to take place on August 28, 2023. The primary outcome measure that will be assessed in this research endeavor is the oxygenation ratio, a metric denoted as the highest PaO2/FiO2 ratio achieved by patients within a 72-hour timeframe following their LTx procedure. We propose that cytokine filtration could enhance the overall outcomes of LTx. Our hypothesis suggests potential improvements in LTx outcome and patient care. ClinicalTrials.gov NCT05526950; https://www.clinicaltrials.gov/study/NCT05526950. PRR1-10.2196/52553.

Simultaneous Lung-abdominal Organ Procurement From Donation After Circulatory Death Donors Reduces Donor Hepatectomy Time.

Prolonged organ procurement time impairs the outcome of donation after circulatory death (DCD) and liver transplantation (LiT). Our transplant team developed a simultaneous, rather than sequential, lung-abdominal organ explantation strategy for DCD donation to prioritize liver procurement. We evaluated whether this change in strategy effectively reduced donor hepatectomy time (dHT), without affecting donor pneumonectomy time (dPT), and influenced LiT and lung transplantation outcome. All lung-abdominal and abdominal-only transplant procedures between 2010 and 2020 were analyzed in this retrospective cohort study. Relationships were assessed between the year of transplant and dHT and dPT (univariate linear regression), 1-y patient and graft survival, primary graft dysfunction, and nonanastomotic biliary strictures (univariate logistic regression). Fifty-two lung-abdominal and 110 abdominal-only DCD procedures were analyzed. A significant decrease in dHT was noted in lung-abdominal (slope -1.14 [-2.14; -0.15], P = 0.026) but not in abdominal-only procedures; dPT did not increase. There were no significant associations between the year of transplant and nonanastomotic biliary strictures frequency, primary graft dysfunction incidence, 1-y patient, and graft survival. Simultaneous organ procurement in multiorgan lung-abdominal DCD procedures is feasible, and effectively shortened dHT without affecting lung transplantation outcome. No impact on LiT outcome was observed; however, larger multicenter studies are needed.

The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation

Background: Primary Graft Dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplant (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were to 1) assess the incidence of severe PGD in an international cohort, 2) evaluate the performance of the most validated PGD risk tool, the RADIAL score, in a contemporary cohort, and 3) redefine clinical risk factors for severe PGD in the current era of HT. Methods: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada, and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis and its calibration was assessed by plotting the percentage of PGD predicted versus observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. Results: A total of 2,746 patients have been enrolled in the registry to date, including 2,015 (73.4%) from North America, and 731 (26.6%) from Europe. 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (p-value for trend by difference sign test = 0.004). The Kaplan Meier estimate for 1-year survival was 75.7% [95%CI 69.4-80.9%] in patients with severe PGD as compared to 94.4% [95% CI 93.5-95.2%] in those without severe PGD (log-rank p-value <0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD with an AUC of 0.53 (95%CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31 – 4.43), durable LVAD support (OR 1.77, 95% CI 1.13 – 2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02 – 1.41) were associated with an increased risk of severe PGD. Conclusions: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

Acute complication posttransplant: primary allograft dysfunction.

Heart transplant is the gold standard treatment for patients with end-stage heart failure, improving both quality of life and survival. Despite advances in donor and recipient management, primary graft dysfunction (PGD) remains the most common cause of morbidity and mortality in the early posttransplant period. This review summarizes recent discoveries in the underlying pathophysiology, risk prediction and management of PGD. The incidence of PGD appears to be rising and it is not clear whether this is due to better recognition or secular changes in transplant practice. The utilization of donation after circulatory death organs for transplant is a further consideration for the development of PGD. Organ transport systems and preservation techniques may help to prevent PGD. As some of the risk factors for developing PGD remain modifiable, we summarize the current evidence for prevention and management of PGD. A better understanding will allow us to appropriately manage donors and recipients to reduce the complex interactions that lead to PGD. The development of an international consortium provides the opportunity for deep phenotyping and development of contemporary risk prediction models for PGD, which may reduce the incidence and consequent early mortality associated with heart transplantation.

Preemptive immune globulin therapy in sensitized lung transplant recipients

BackgroundSensitized lung transplant recipients are at increased risk of developing donor-specific antibodies, which have been associated with acute and chronic rejection. Perioperative intravenous immune globulin has been used in sensitized individuals to down-regulate antibody production. MethodsWe compared patients with a pre-transplant calculated panel reactive antibody ≥25% who did not receive preemptive immune globulin therapy to a historical control that received preemptive immune globulin therapy. Our cohort included 59 patients, 17 patients did not receive immune globulin therapy and 42 patients received therapy. ResultsDonor specific antibody development was numerically higher in the non-immune globulin group compared to the immune globulin group (58.8% vs 33.3%, respectively, odds ratio 2.80, 95% confidence interval [0.77, 10.79], p = 0.13). Median time to antibody development was 9 days (Q1, Q3: 7, 19) and 28 days (Q1, Q3: 7, 58) in the non-immune globulin and immune globulin groups, respectively. There was no significant difference between groups in the incidence of primary graft dysfunction at 72 h post-transplant or acute cellular rejection, antibody-mediated rejection, and chronic lung allograft dysfunction at 12 months. ConclusionThese findings are hypothesis generating and emphasize the need for larger, randomized studies to determine association of immune globulin therapy with clinical outcomes.

The Role of Recipient Thyroid Hormone Supplementation in Primary Graft Dysfunction After Heart Transplantation: A Propensity-Adjusted Analysis

To investigate whether recipient administration of thyroid hormone (liothyronine [T3]) is associated with reduced rates of primary graft dysfunction (PGD) after orthotopic heart transplantation. Retrospective cohort study. Single-center, university hospital. Adult patients undergoing orthotopic heart transplantation. A total of 609 adult heart transplant recipients were divided into 2 cohorts: patients who did not receive T3 (no T3 group, from 2009 to 2014), and patients who received T3 (T3 group, from 2015 to 2019). Propensity-adjusted logistic regression was performed to assess the association between T3 supplementation and PGD. After applying exclusion criteria and propensity-score analysis, the final cohort included 461 patients. The incidence of PGD was not significantly different between the groups (33.9% no T3 group v 40.8% T3 group; p=0.32). Mortality at 30 days (3% no T3 group v 2% T3 group; p=0.53) and 1 year (10% no T3 group v 12% T3 group; p=0.26) were also not significantly different. When assessing the severity of PGD, there were no differences in the groups' rates of moderate PGD (not requiring mechanical circulatory support other than an intra-aortic balloon pump) or severe PGD (requiring mechanical circulatory support other than an intra-aortic balloon pump). However, segmented time regression analysis revealed that patients in the T3 group were less likely to develop severe PGD. These findings indicated that recipient single-dose thyroid hormone administration may not protect against the development of PGD, but may attenuate the severity of PGD.

Substance Use-Associated Mortality among Heart Donors after the COVID-19 National Emergency Increased but Did Not Affect Peri-Transplant Outcomes

The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

Three year post heart transplant outcomes of desensitized durable mechanical circulatory support patients

The risks and benefits of desensitization therapy (DST) in highly sensitized mechanical circulatory support (MCS) patients are not well known. We investigated 3 year post-transplant outcomes of desensitized durable MCS patients. Among 689 consecutively enrolled heart transplantation recipients between 2010 and 2016, we categorized them into Group A (desensitized MCS patients, n=21), Group B (desensitized non-MCS patients, n=28) and Group C (all nondesensitized patients, n=640). Post-transplant outcomes included the incidence of primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, antibody mediated rejection (AMR) and infectious complications. The types of DST in Groups A and B were similar and included combinations of rituximab/intravenous immunoglobulin and plasmapheresis/bortezomib. Group A, compared with Group B, showed significantly higher pre-DST panel reactive antibody (PRA) (92.2±9.8 vs. 83.3±15.6, P=0.007) and higher PRA reduction after DST (-22.2±26.9 vs. -6.3±7.5, P=0.015). Groups A and C showed comparable primary graft dysfunction, 3-year survival, freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, any treated rejection, acute cellular rejection, and AMR. Although statistically not significant, Group A showed numerically higher 3-year freedom from AMR than Group B. Infectious complications were similar in both Groups A and B. DST for MCS patients showed significant PRA reduction, resulting in an expansion of the donor pool. The post-transplant outcome of desensitized MCS patients showed comparable clinical outcomes to non-desensitized control patients in the same study period, revealing the safety and efficacy of DST.

(143) Impact of the 2018 Adult Heart Allocation Policy Change on the Incidence of Primary Graft Dysfunction after Heart Transplantation

(143) Impact of the 2018 Adult Heart Allocation Policy Change on the Incidence of Primary Graft Dysfunction after Heart Transplantation

Impact of pre-lung transplant statin use on the development of primary graft dysfunction.

Primary graft dysfunction (PGD) is a common occurrence following lung transplantation and contributes to short- and long-term morbidity and mortality. Current management strategies are limited, and robust data to support their use is lacking. Preventative strategies attenuating the recipient's inflammatory state suggest statin therapy may decrease the incidence and severity of PGD. This study aims to evaluate the impact of pre-transplant statin use on the incidence and severity of PGD following lung transplantation. A retrospective cohort study was performed evaluating all patients undergoing bilateral lung transplantation from September 2012 to December 2019. The primary outcome was the incidence of PGD by grade, defined as the highest grade of PGD experienced in the first 72h. Secondary outcomes included length of intensive care unit and hospital stays and mortality. Of the 357 patients included in the study, 107 received statin therapy prior to transplant (statin group) and 250 did not (no statin group). PGD occurred in 257 (72%) patients; in the entire cohort, 99 (28%) patients experienced PGD grade 1, 59 (17%) grade 2, and 99 (28%) grade 3. A significantly lower incidence of PGD was observed in the statin group (64.5% vs 75.2%, p= 0.039); however, the association did not remain significant on multinominal analysis for an overall incidence of any PGD (p= 0.275) or incidence of severe PGD (p= 0.240). Statin intensity was not associated with the development of PGD. Pre-transplant statin therapy did not appear to impact the development of PGD following lung transplantation. Future prospective studies should further evaluate the impact of statin intensity and duration on the incidence and severity of PGD.

Effect of Preoperative Right Ventricular Dysfunction on Heart Transplantation Outcomes

We investigated if the occurrence of preoperative right ventricular dysfunction is capable of influencing heart transplant results in terms of in-hospital mortality, incidence of primary graft dysfunction, and follow-up mortality. We retrospectively analyzed 517 patients who underwent heart transplant between January 2000 and December 2020. We defined right ventricular dysfunction (RVD), as central venous pressure (CVP) > 15 mm Hg and CVP/pulmonary capillary wedge pressure ratio > 0.63. We identified 2 subgroups in our population: 33 patients with preoperative RVD and 484 patients without RVD. In-hospital mortality was 7.9%. Severe early graft failure occurred in 6.6% of patients, with 26 patients (5.1%) needing intra-aortic balloon pump and 17 patients (3.3%) needing extracorporeal membrane oxygenation support. Clinical variables that significantly influenced in-hospital mortality were age, peripheral artery disease, and bilirubin > 1.5 mg/dL, while hemodynamic variables influencing in-hospital mortality were CVP (odds ratio [OR], 1.09 [confidence interval {CI}, 1.03-1.15], P=.004], pulmonary artery systolic pressure (OR, 1.02 [CI, 1.00-1.04], P=.05), CVP/pulmonary capillary wedge pressure ratio (OR, 2.78 [CI, 1.14-6.80], P=.025), pulmonary vascular resistance (OR, 1.15 [CI, 1.01-1.32], P=.042), transpulmonary gradient (TPG) (OR, 1.11 [CI, 1.03-1.18], P=.003) , diastolic transpulmonary gradient (OR, 1.10 [CI, 1.02-1.20], P=.015], together with right ventricular dysfunction (OR, 3.56 [CI, 1.44-8.80], P=.011). On the other hand, clinical variables influencing the incidence of early graft failure were body mass index (calculated as weight in kilograms divided by height in meters squared) > 30, peripheral artery disease, bilirubin > 1.5 mg/dL, Model for End-Stage Liver Disease score excluding international normalized ratio before transplant, and preoperative extracorporeal membrane oxygenation support, while hemodynamic variables were pulmonary arterial systolic pressure (OR, 1.03 [CI, 1.00-1.05], P=.016), TPG (OR, 1.08 [1.01-1.17], P=.03), and right ventricular dysfunction (OR, 3.00 [CI, 1.07-8.40] P=.046). On the multivariable analysis, RVD and TPG were independent predictors of in-hospital mortality, while only TPG was a predictor of early graft failure. Follow-up mortality was 38.7% and was influenced by recipient age, recipient body mass index, and preoperative diabetes. Moreover, 1-, 5-, and 10-year survival of patients with preoperative RVD was significantly worse than patients without RVD (log-rank=0.001). In our population, RVD influenced both in-hospital and long-term results after heart transplant. For these reasons, it appears crucially important to optimize preoperative right ventricular function to improve these patients' outcomes.