Risk Of Primary Graft Dysfunction Research Articles

Early Outcomes in Patients With LVAD Undergoing Heart Transplant via Use of the SherpaPak Cardiac Transport System.

Heart transplant (HT) in recipients with left ventricular assist devices (LVADs) is associated with poor early post-HT outcomes, including primary graft dysfunction (PGD). As complicated heart explants in recipients with LVADs may produce longer ischemic times, innovations in donor heart preservation may yield improved post-HT outcomes. The SherpaPak Cardiac Transport System is an organ preservation technology that maintains donor heart temperatures between 4 °C and 8 °C, which may minimize ischemic and cold-induced graft injuries. This analysis sought to identify whether the use of SherpaPak versus traditional cold storage was associated with differential outcomes among patients with durable LVAD undergoing HT. Global Utilization and Registry Database for Improved Heart Preservation-Heart (NCT04141605) is a multicenter registry assessing post-HT outcomes comparing 2 methods of donor heart preservation: SherpaPak versus traditional cold storage. A retrospective review of all patients with durable LVAD who underwent HT was performed. Outcomes assessed included rates of PGD, post-HT mechanical circulatory support use, and 30-day and 1-year survival. SherpaPak (n=149) and traditional cold storage (n=178) patients had similar baseline characteristics. SherpaPak use was associated with reduced PGD (adjusted odds ratio, 0.56 [95% CI, 0.32-0.99]; P=0.045) and severe PGD (adjusted odds ratio, 0.31 [95% CI, 0.13-0.75]; P=0.009), despite an increased total ischemic time in the SherpaPak group. Propensity matched analysis also noted a trend toward reduced intensive care unit (SherpaPak 7.5±6.4 days versus traditional cold storage 11.3±18.8 days; P=0.09) and hospital (SherpaPak 20.5±11.9 days versus traditional cold storage 28.7±37.0 days; P=0.06) lengths of stay. The 30-day and 1-year survival was similar between groups. SherpaPak use was associated with improved early post-HT outcomes among patients with LVAD undergoing HT. This innovation in preservation technology may be an option for HT candidates at increased risk for PGD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04141605.

(63) - Decreased Risk of Primary Graft Dysfunction with the SherpaPak Cardiac Transport System in Pediatric Heart Transplant Recipients

(63) - Decreased Risk of Primary Graft Dysfunction with the SherpaPak Cardiac Transport System in Pediatric Heart Transplant Recipients

Impact of Blood Products Transfusion on Patients in the Immediate Post-Lung Transplant Period: A Cohort Study.

BACKGROUND Anemia is common in post-transplant patients. Blood product transfusion is associated with mortality and rejection in solid organ transplants. In lung transplant recipients, transfusion predisposes to primary graft dysfunction (PGD). The adverse effects and associated mortality of perioperative transfusions in lung transplant recipients have not been evaluated. This study examined the effects of perioperative blood transfusions in lung transplant recipients. MATERIAL AND METHODS We conducted a retrospective study of the effects of blood product transfusions in patients who received single- or double-lung transplantation at Houston Methodist Hospital between August 2017 and September 2019. Univariable and multiple logistic regression modeling were used to determine the characteristics associated with single events as well as a composite outcome within 30 days (including mortality, acute myocardial infarction, acute stroke, lower respiratory tract infection, urinary tract infection, surgical site infections, or PGD). RESULTS A total of 232 patients received lung transplants between December 2015 and September 2019 at our center. Univariable analysis revealed an increased risk of PGD (P<0.001), more mechanical ventilation days (P<0.001), more ICU days post-transplant (P<0.001), and greater need for ECMO support (P=0.001) in patients who received blood product transfusions. In univariate analysis, the composite outcome was also more common (P=0.01) in patients who received any transfusion perioperatively. A total of 7 patients died within 30 days from transplant, and they were all in the transfused group. CONCLUSIONS Among lung transplant recipients, PGD, ICU days, need for mechanical ventilation and ECMO support, and total composite events were significantly greater in patients who received blood transfusion perioperatively.

Impact of controlled hypothermic preservation on outcomes following heart transplantation

BackgroundSevere primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant. but the impact of donor organ preservation conditions on severity of PGD and survival have not been well characterized. MethodsData from US adult heart-transplant recipients in the GUARDIAN-Heart registry (NCT04141605) were analyzed to quantify PGD severity (stratified by ISHLT definition), mortality, and associated risk factors. The independent contributions of organ-preservation method (traditional ice storage versus controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. ResultsAmong 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% (37/559) versus 10.4% (47/452), p=0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% (17/281) versus 12.1% (34/281) respectively; p=0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p<0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. ConclusionsSevere PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries

IntroductionIschaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart...

The role of lung-restricted autoantibodies in the development of primary and chronic graft dysfunction

Lung transplantation is a life-saving treatment for both chronic end-stage lung diseases and acute respiratory distress syndrome, including those caused by infectious agents like COVID-19. Despite its increasing utilization, outcomes post-lung transplantation are worse than other solid organ transplants. Primary graft dysfunction (PGD)—a condition affecting more than half of the recipients post-transplantation—is the chief risk factor for post-operative mortality, transplant-associated multi-organ dysfunction, and long-term graft loss due to chronic rejection. While donor-specific antibodies targeting allogenic human leukocyte antigens have been linked to transplant rejection, the role of recipient's pre-existing immunoglobulin G autoantibodies against lung-restricted self-antigens (LRA), like collagen type V and k-alpha1 tubulin, is less understood in the context of lung transplantation. Recent studies have found an increased risk of PGD development in lung transplant recipients with LRA. This review will synthesize past and ongoing research—utilizing both mouse models and human subjects—aimed at unraveling the mechanisms by which LRA heightens the risk of PGD. Furthermore, it will explore prospective approaches designed to mitigate the impact of LRA on lung transplant patients.

Hypothermic oxygenated perfusion (HOPE) safely and effectively extends acceptable donor heart preservation times: Results of the Australian and New Zealand trial

BackgroundCold static storage (CSS) preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts. MethodsWe conducted a non-randomised, single arm, multi-center investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6-8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation Registry. ResultsWe performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. 30-day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients. ConclusionsHOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations.

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.

HLA sensitization is associated with an increased risk of primary graft dysfunction after heart transplantation

Consecutive adult HT recipients (n=596) from 1/2015to12/2019 at 2 US centers were included. Severity of PGD was based on the 2014 International Society for Heart and Lung Transplantationconsensus statement. For each recipient, unacceptable HLA antigens were obtained and locus-specific cPRA (cPRA-LS) and pre-HT donor-specific antibodies (DSA) were assessed. Univariable logistic modeling showed that peak cPRA-LS for all loci and HLA-A was associated with increased severity of PGD as an ordinal variable (all loci: OR 1.78, 95% CI: 1.01-1.14, p=0.025, HLA-A: OR 1.14, 95% CI: 1.03-1.26, p=0.011). Multivariable analysis showed peak cPRA-LS for HLA-A, recipient beta-blocker use, total ischemic time, donor age, prior cardiac surgery, and United Network for Organ Sharing status 1 or 2 were associated with increased severity of PGD. The presence of DSA to HLA-B was associated with trend toward increased risk of mild-to-moderate PGD (OR 2.56, 95% CI: 0.99-6.63, p=0.053), but DSA to other HLA loci was not associated with PGD. Sensitization for all HLA loci, and specifically HLA-A, is associated with an increased severity of PGD. These factors should be included in pre-HT risk stratificationto minimize the risk of PGD.

Monitoring regulatory T cells as a prognostic marker in lung transplantation.

Lung transplantation is the major surgical procedure, which restores normal lung functioning and provides years of life for patients suffering from major lung diseases. Lung transplant recipients are at high risk of primary graft dysfunction, and chronic lung allograft dysfunction (CLAD) in the form of bronchiolitis obliterative syndrome (BOS). Regulatory T cell (Treg) suppresses effector cells and clinical studies have demonstrated that Treg levels are altered in transplanted lung during BOS progression as compared to normal lung. Here, we discuss levels of Tregs/FOXP3 gene expression as a crucial prognostic biomarker of lung functions during CLAD progression in clinical lung transplant recipients. The review will also discuss Treg mediated immune tolerance, tissue repair, and therapeutic strategies for achieving in-vivo Treg expansion, which will be a potential therapeutic option to reduce inflammation-mediated graft injuries, taper the toxic side effects of ongoing immunosuppressants, and improve lung transplant survival rates.

Donor heart ischemic time can be extended beyond 9 hours using hypothermic machine perfusion in sheep

The global shortage of donor hearts available for transplantation is a major problem for the treatment of end-stage heart failure. The ischemic time for donor hearts using traditional preservation by standard static cold storage (SCS) is limited to approximately 4 hours, beyond which the risk for primary graft dysfunction (PGD) significantly increases. Hypothermic machine perfusion (HMP) of donor hearts has been proposed to safely extend ischemic time without increasing the risk of PGD. Using our sheep model of 24 hours brain death (BD) followed by orthotopic heart transplantation (HTx), we examined post-transplant outcomes in recipients following donor heart preservation by HMP for 8 hours, compared to donor heart preservation for 2 hours by either SCS or HMP. Following HTx, all HMP recipients (both 2 hours and 8 hours groups) survived to the end of the study (6 hours after transplantation and successful weaning from cardiopulmonary bypass), required less vasoactive support for hemodynamic stability, and exhibited superior metabolic, fluid status and inflammatory profiles compared to SCS recipients. Contractile function and cardiac damage (troponin I release and histological assessment) was comparable between groups. Overall, compared to current clinical SCS, recipient outcomes following transplantation are not adversely impacted by extending HMP to 8 hours. These results have important implications for clinical transplantation where longer ischemic times may be required (e.g., complex surgical cases, transport across long distances). Additionally, HMP may allow safe preservation of "marginal" donor hearts that are more susceptible to myocardial injury and facilitate increased utilization of these hearts for transplantation.

(403) Pre-Transplantation Recipient Blood Transfusions Increase the Risk of Primary Graft Dysfunction Following Lung Transplantation

(403) Pre-Transplantation Recipient Blood Transfusions Increase the Risk of Primary Graft Dysfunction Following Lung Transplantation

The impact of pre-existing hematologic disorders on morbidity and mortality following heart transplantation: Focus on early graft dysfunction.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure, providing excellent long-term outcomes. However, postoperative outcomes are limited by bleeding, infections, and primary graft dysfunction (PGD) that contribute to early mortality after HT. HT candidates with pre-existing hematologic disorders, bleeding, and clotting, may represent a higher risk population. We assessed the short- and long-term outcomes of patients with pre-existing hematologic disorders undergoing HT. Medical records of all adult patients who received HT from January 2010 to December 2019 at our institution were retrospectively reviewed. Hematologic disorders were identified via chart review and adjudicated by a board-certified hematologist. Inverse probability weighting and multivariable models were used to adjust for potential pretransplant confounders. Four hundred and ninety HT recipients were included, of whom 29 (5.9%) had a hematologic disorder. Hematologic disorders were associated with severe PGD requiring mechanical circulatory support (aOR 3.15 [1.01-9.86]; p=.049), postoperative infections (aOR 2.93 [1.38-6.23]; p=.01), and 3-year acute cellular rejection (ACR) (≥1R/1B) (aSHR 2.06 [1.09-3.87]; p=.03). There was no difference in in-hospital mortality (aOR 1.23 [.20-7.58], p=.82) or 3-year mortality (aHR 1.58 [.49-5.12], p=.44). Patients with hematologic disorders undergoing HT are at increased risk of severe PGD, postoperative infections, and ACR, while in-hospital and 3-year mortality remain unaffected.

Potential Role of Computed Tomography Volumetry in Size Matching in Lung Transplantation

Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction. Donors from the local organ procurement organization and recipients from our hospital from 2012 to 2018 were included if their CT exams were available. The CT lung volumes and plethysmography total lung capacity were measured and compared with predicted total lung capacity using Bland Altman methods. We used logistic regression to predict the need for surgical graft reduction and ordinal logistic regression to stratify the risk for primary graft dysfunction. A total of 315 transplant candidates with 575 CT scans and 379 donors with 379 CT scans were included. The CT lung volumes closely approximated plethysmography lung volumes and differed from the predicted total lung capacity in transplant candidates. In donors, CT lung volumes systematically underestimated predicted total lung capacity. Ninety-four donors and recipients were matched and transplanted locally. Larger donor and smaller recipient lung volumes estimated by CT predicted a need for surgical graft reduction and were associated with higher primary graft dysfunction grade. The CT lung volumes predicted the need for surgical graft reduction and primary graft dysfunction grade. Adding CT-derived lung volumes to the donor-recipient matching process may improve recipients' outcomes.

Donor hyperoxia is a novel risk factor for severe cardiac primary graft dysfunction

Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT. A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n=1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation. Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort. Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.

Postreperfusion Pulmonary Artery Pressure Indicates Primary Graft Dysfunction After Lung Transplant

BackgroundPrimary graft dysfunction is a risk factor of early mortality after lung transplant. Models identifying patients at high risk for primary graft dysfunction are limited. We hypothesize high postreperfusion systolic pulmonary artery pressure is a clinical marker for primary graft dysfunction. MethodsThis is a retrospective review of 158 consecutive lung transplants performed at a single academic center from January 2020 through July 2022. Only bilateral lung transplants were included and patients with pretransplant extracorporeal life support were excluded. ResultsPrimary graft dysfunction occurred in 42.3% (n = 30). Patients with primary graft dysfunction had higher postreperfusion systolic pulmonary artery pressure (41 ± 9.1 mm Hg) than those without (31.5 ± 8.8 mm Hg) (P < .001). Logistic regression showed postreperfusion systolic pulmonary artery pressure is a predictor for primary graft dysfunction (odds ratio 1.14, 95% CI 1.06-1.24, P < .001). Postreperfusion systolic pulmonary artery pressure of 37 mm Hg was optimal for predicting primary graft dysfunction by Youden index. The receiver operating characteristic curve of postreperfusion systolic pulmonary artery pressure at 37 mm Hg (sensitivity 0.77, specificity 0.78, area under the curve 0.81), was superior to the prereperfusion pressure curve at 36 mm Hg (sensitivity 0.77, specificity 0.39, area under the curve 0.57) (P < .01). ConclusionsElevated postreperfusion systolic pulmonary artery pressure after lung transplant is predictive of primary graft dysfunction. Postreperfusion systolic pulmonary artery pressure is more indicative of primary graft dysfunction than prereperfusion systolic pulmonary artery pressure. Using postreperfusion systolic pulmonary artery pressure as a positive signal of primary graft dysfunction allows earlier intervention, which could improve outcomes.

Donor substance use and lung transplantation: A single center experience

BackgroundLung transplantation (LT) demand outpaces supply. Consequently, extended criteria for donor selection are used, resulting in LT from donors with a history of substance use (SU). The aim of this study is to assess the association between donor SU and short-term LT outcomes. MethodsWe obtained recipient and donor data for LTs performed between January 2014 to January 2019 from electronic health records and the United Network for Organ Sharing (UNOS) database. We defined SU as cigarette/e-cigarette smoking, illicit SU (cannabis, cocaine, opioids, amphetamines), or heavy alcohol use (2+ alcoholic drinks per day). Our primary outcome was late high-grade primary graft dysfunction (PGD), which we defined as grade 2-3 PGD between 48-72 hours post-LT. Secondary outcomes included mechanical ventilation (MV) hours, intensive care unit (ICU) length of stay (LOS), hospital LOS, number of bronchoscopies, cumulative acute rejection (CAR) score in the first year after LT, and overall survival (OS). ResultsA total of 352 LTs were included in this study. On multivariable regression, we found that any donor cigarette smoking was associated with increased odds of late high grade PGD (p=0.021), while any donor cannabis use was associated with reduced odds of late high grade PGD (p=0.002). There was no association between any donor SU and secondary outcomes. ConclusionsDonor cigarette use was associated with higher risk for PGD. Our findings may suggest a history of donor cannabis use and other illicit SU are not associated with PGD or worse OS.

Hypothermic Ex Vivo Perfusion of Donor Hearts can Safely Preserve Post‐transplant Cardiac Function in Sheep for 8 Hours

IntroductionHeart transplantation (HTx) is the primary therapy for end‐stage heart failure. For HTx, donor hearts are typically preserved on ice in a cooler (devoid of oxygen), termed cold static storage (CSS). CSS beyond 4 hrs increases the risk of primary graft dysfunction (PGD), the leading cause of early death post‐HTx. Hypothermic ex vivo perfusion (HEVP) of donor hearts allows oxygen delivery during preservation, and we hypothesise, may safely extend donor heart preservation time without increasing PGD risk. We sought to compare post‐HTx recipient survival, cardiac contractility, mitochondrial function, and injury following donor heart preservation by CSS (2 hrs) or HEVP (2 and 8 hrs).MethodsBrain death was induced in donor sheep for 24 hrs, hearts were then preserved by a) CSS for 2 hrs (n=8), b) HEVP for 2 hrs (n=6), or c) HEVP for 8 hrs (n=7). Orthotopic HTx was performed in matched recipients, with progressive hemodynamic management and monitoring for 6 hrs post‐HTx. Recipient cardiac function was assessed by echocardiography, and troponin I levels were measured in plasma. Mitochondrial function, in vitro contractile responses to noradrenaline (trabeculae), and histopathological changes were determined in cardiac tissue collected at end‐study.ResultsAll HEVP recipients survived to 6 hrs post‐HTx, compared to 6/8 CSS recipients. HEVP (2 and 8 hrs) recipients required less vasoactive support for adequate hemodynamic function, and exhibited reduced blood lactate levels compared to CSS. Post‐HTx cardiac function and troponin I levels were comparable between groups over time, however improved contractile responses to noradrenaline were observed in isolated trabeculae from 2 and 8 hr HEVP hearts. Cardiac mitochondrial function was similar between all groups, except for the 2 hrs HEVP left ventricle, where greater improvements in mitochondrial membrane potential generation were observed. Regardless of preservation technique, histological scores revealed widespread cardiac injury (e.g. myocytolysis and neutrophil infiltration).ConclusionDonor heart preservation by HEVP shows promising post‐HTx outcomes in comparison to CSS in a sheep HTx model. HEVP can be safely extended up to 8 hrs, without compromising post‐HTx recipient survival, cardiac contractile or mitochondrial function. HEVP may assist in overcoming limitations in preservation time associated with HTx, without increasing PGD risk. The Australian Non‐Ischemic Heart Preservation (NIHP) trial is currently assessing extended HEVP in clinical HTx (ACTRN12620000595910p).

Spontaneous Donor Hypothermia is Independently Associated with Increased Risk of Primary Graft Dysfunction After Heart Transplant

<h3>Purpose</h3> Multiple donor and recipient characteristics contribute to the pathogenesis of primary graft dysfunction (PGD) after heart transplantation (HT). The purpose of this study was to determine the association between spontaneous donor hypothermia and PGD. <h3>Methods</h3> Consecutive adult HT recipients (n=1106) from 3/2012 to 12/2019 at two high-volume centers were included. Severe PGD was defined using the ISHLT consensus statement. Donor physiologic parameters were collected from the United Network for Organ Sharing Donor Management Goals registry. Univariable and multivariable logistic modeling were performed. <h3>Results</h3> Donors were predominantly male (66.6%), with a mean donor age of 34.9±13.0 years. Severe PGD occurred in 66 (6.0%) patients. Patients with severe PGD were more likely to receive organs from older donors (38.0±13.0 vs. 34.7±12.7 years, p=0.04) and lower donor to recipient heart mass ratio (1.00±0.15 vs. 1.05±0.20, p=0.048). Single variable modeling showed predicted heart mass ratio, donor age, and spontaneous donor hypothermia defined as less than 36 degrees Celsius at time of procurement to be significant predictors of severe PGD. Multivariable modeling showed that spontaneous donor hypothermia (OR 2.21, 95% CI: [1.21-4.03], p=0.01) was significantly associated with severe PGD after adjusting for donor age and predicted heart mass ratio. There was no increased incidence of severe PGD with spontaneous donor hypothermia either at time of referral (OR: 1.35, 95% CI: [0.78-2.35], p=0.28) or 12 to 18 hours later (OR: 1.16, 95% CI: [0.51-2.66], p=0.71). Spontaneous donor hyperthermia defined as greater than 37.5 degrees Celsius at time of procurement was not associated with severe PGD (OR: 1.69, 95% CI: [0.64-4.45], p=0.29). <h3>Conclusion</h3> Spontaneous donor hypothermia at time of organ procurement is associated with an increased risk of severe PGD.

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.