Incidence Of Primary Graft Dysfunction Research Articles

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

<h3>Purpose</h3> Primary Graft Dysfunction (PGD) is a leading cause of short-term mortality after heart transplantation (HT). Available registries lack data to identify PGD based on post-HT hemodynamics and mechanical circulatory support (MCS). Herein, we describe the development of a multicenter International Consortium on PGD: a registry designed to quantify the incidence, risk factors, and impact of PGD, in order to develop contemporary risk prediction models. <h3>Methods</h3> We are currently collecting data from 10 participating sites in Europe and North America which will include clinical data from an estimated 3,826 HT recipients (Table 1). We defined PGD using the ISHLT 2014 consensus criteria. Our complete consortium will include data on baseline donors and recipients demographics, pre and post-HT hemodynamics, and the type and duration of MCS after HT. We will use regression models and supervised machine learning (ML) algorithms to develop risk prediction models that reflect the contemporary landscape of HT. <h3>Endpoints</h3> To date, we have collected preliminary data on 2,178 single-organ HT recipients between 2010 - 2020 (57% of the anticipated final sample size). Our consortium cohort consists of patients with age of 54 ± 12 years, of whom 24.7% (n=537) are female. Pre-transplant MCS included IABP in 3.6% (n=80), ECMO in 1.4% (n=30), and durable LVAD in 8.3% (n=181). Donor age was 37 ± 13 years and ischemic time was 3.4 ± 1.0 hours. A total of 167 (7.7%) recipients met criteria for severe PGD and 76 (6.5%) for moderate PGD. One-year survival was 67% (95% CI 59 - 74%) and 93% (95% CI 92 - 94%) in patients with and without severe PGD, respectively. We aim to develop contemporary tools for risk stratification of HT recipients for incident PGD. Our multicenter, international consortium allows for comprehensive phenotyping of HT recipients based upon a standardized definition of PGD to accurately understand PGD incidence, risk factors, and outcomes in the era of MCS. <h3>Interim Results</h3> To date, we have collected 106 variables on 2,476 single-organ HT recipients from 2010 to 2020 (Figure 1A). Mean age of cohort is 53.9 ± 12.3 years; 25% female, 330 recipients from Canada, 518 from Europe, and 1628 from the US. Pre-transplant MCS included IABP in 8.4% (n=207), ECMO in 1.3% (n=33), and durable LVAD in 32.1% (n=795) (Figure 1B). Average donor age was 36.4 ± 13.0 years with mean ischemic time 3.4 ± 1.1 hours. A total of 214 (8.6%) of recipients met criteria for severe PGD, requiring VA-ECMO (n=186), RVAD (n=28), or both (n=3). Among 1811 patients with adequate follow up data, 1-year survival was 78% (95% CI 72% – 83%) in patients with severe PGD, and 95% (95% CI 94% – 96%) in those without severe PGD (Figure 1C). The previously-published RADIAL PGD risk score performed poorly in our cohort, with an AUC of 0.50 for severe PGD(Figure 1D).

Primary heart dysfunction is greater with combined heart and lung compared with isolated heart procurement

ObjectiveCombined heart and lungs (CHL) procurement differs from isolated heart (IH) procurement in several aspects, including lung recruitment, cannulation, and preservation requirements. We aimed to investigate whether CHL versus IH procurement contributes to the development of primary graft dysfunction (PGD) after heart transplantation (HT). MethodsBetween 1999 and 2019, we assessed 175 patients undergoing HT at a single center. Patients were divided into IH (n = 61) or CHL (n = 114) procurement groups. End points included PGD (defined according to the International Society for Heart and Lung Transplantation consensus statement) and long-term survival. ResultsThe incidence of PGD was significantly greater in CHL recipients compared with IH recipients (53.5% vs 16.4%, P < .001). Multivariable analysis showed that CHL procurement was independently associated with a significant 4.6-fold increased risk for PGD (95% confidence interval, 2.1-11, P < .001). Univariable and multivariable analyses showed that the overall survival was not significantly affected by the procurement group (log-rank P = .150, hazard ratio, 1.13; 95% confidence interval, 0.68-1.88, P = .646). The simultaneous procurement of abdominal organs was not associated with an increased risk of PGD in HT recipients. These results remained consistent in a propensity-matched analysis. ConclusionsCombined procurement of heart and lungs is independently associated with an increased risk of PGD. Further prospective studies are needed to validate this hypothesis-generating study.

Effect on the donor lungs of using abdominal normothermic regional perfusion in controlled donation after circulatory death.

Controlled donation after circulatory death (cDCD) donors are becoming a common source of organs for transplantation globally. However, the graft survival rate of cDCD abdominal organs is inferior to that of organs from brain-dead donors. The rapid retrieval (RR) technique is used by most donor organ procurement teams. The abdominal normothermic regional perfusion (A-NRP) technique has been implemented to minimize warm ischaemic damage to the abdominal organs. However, there is limited information on the effect of A-NRP on the quality of the donor lungs. This study aimed to compare lung transplantation outcomes using lungs procured from cDCD donors using the A-NRP and abdominal RR techniques. A single-centre retrospective analysis of consecutive transplant recipients of cDCD lungs from June 2013 to December 2019 was performed. The recipients were divided into 2 cohorts according to the abdominal procurement technique used. The recipient and donor characteristics (age, sex, cause of brain injury, warm ischaemic time, diagnosis, lung allocation score and other factors), incidence of primary graft dysfunction and early survival were monitored. Twenty-eight consecutive lung transplantation recipients were identified (median age 59 years; 61% male); 14 recipients received lungs using the A-NRP and 14 using abdominal RR for abdominal organ retrieval. There were no significant differences in the baseline characteristics, primary graft dysfunction (P = 0.70), hospital mortality (P = 1.0) and 1-year survival rate (P = 1.0) between the 2 groups. No difference was observed in lung transplantation outcomes irrespective of the abdominal organ procurement technique used (A-NRP or abdominal RR).

HIGHER DONOR PAO2/FIO2 RATIO APPEARS TO BE ASSOCIATED WITH INCREASED INCIDENCE OF PRIMARY GRAFT DYSFUNCTION IN LUNG TRANSPLANT RECIPIENTS

SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Severe primary graft dysfunction (PGD) is the most common cause of early mortality in lung transplantation and is a significant risk factor for the development of chronic lung allograft dysfunction. Although numerous risk factors for PGD have been identified, little data exists on the impact of donor mechanical ventilation parameters on the incidence of PGD. Given the detrimental effects of hyperoxia on the pulmonary alveolar epithelium and capillary endothelium, we hypothesized that donor hyperoxia may increase the risk of PGD. METHODS: We reviewed 175 lung transplants performed at our institution from 2012 to 2019. The last reported arterial blood gas and ventilator parameters in the UNOS database were collected. Recipient PGD grade was calculated at 48-72 hours post-transplant. Other transplant variables were collected: intraoperative cardiopulmonary bypass use, donor smoking history, as well as recipient diagnosis and BMI. RESULTS: Mean donor P/F ratio was lower for recipients with PGD grades 0-2 (438±69) vs. PGD grade 3 (469±64.8);p=0.006. There was a significant difference in the mean donor P/F ratio between the extremes, PGD grade 0 (430±65.5) and the PGD grade 3 (469±64.8);p=0.005. Notably, the incidence of PGD grade 3 increased with an increase in the donor P/F ratio, with the highest incidence of PGD grade 3 observed when the P/F ratio was >500 (Fig. 1). Mean donor tidal volume (ml/kg of ideal body weight) was similar among all groups: 8.7, 8.8, 8.9, and 8.4 for PGD 0, 1, 2, or 3, respectively. CONCLUSIONS: Recipients with PGD grade 3 had significantly higher donor P/F ratios than those with PGD grade 0-2. Donor P/F ratio >500 was associated with an increased incidence of PGD grade 3. CLINICAL IMPLICATIONS: This preliminary data suggests that donor hyperoxia may lead to an increased risk for severe PGD. More research is needed to further delineate the effects of donor mechanical ventilation strategies and transplant recipient outcomes. DISCLOSURES: No relevant relationships by Kareem Ahmad, source=Web Response No relevant relationships by Shambhu Aryal, source=Web Response Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 Added 06/12/2020 by Anne Brown, source=Web Response, value=Honoraria Advisory Committee Member relationship with Vertex Please note: $1001 - $5000 Added 06/12/2020 by Anne Brown, source=Web Response, value=Honoraria Advisory Committee Member relationship with Promedior Please note: $5001 - $20000 Added 06/12/2020 by Anne Brown, source=Web Response, value=Consulting fee No relevant relationships by Vikramjit Khangoora, source=Web Response Advisory Committee Member relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 04/16/2020 by Christopher King, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Actelion Please note: $5001 - $20000 Added 04/16/2020 by Christopher King, source=Web Response, value=Honoraria Advisory Committee Member relationship with Actelion Please note: $1001 - $5000 Added 04/27/2020 by Christopher King, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Boehringer Ingelheim pharmaceuticals Please note: $1001 - $5000 Added 04/27/2020 by Christopher King, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Actelion Please note: $1001 - $5000 Added 04/27/2020 by Christopher King, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 04/27/2020 by Christopher King, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 - $5000 Added 04/27/2020 by Christopher King, source=Web Response, value=Honoraria Advisory Committee Member relationship with United therapeutics Please note: $1001 - $5000 Added 04/27/2020 by Christopher King, source=Web Response, value=Consulting fee Consultant relationship with Veracyte Please note: $1001 - $5000 Added 04/03/2020 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with United Therapeutics Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Roche-Genentech Please note: $5001 - $20000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boerhinger-Ingelheim Please note: $20001 - $100000 Added 05/27/2020 by Steven Nathan, source=Web Response, value=Honoraria Scientific Medical Advisor relationship with Johnson & Johnson Please note: $1001 - $5000 Added 04/22/2020 by Oksana Shlobin, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Bayer Please note: $1001 - $5000 Added 04/22/2020 by Oksana Shlobin, source=Web Response, value=Grant/Research Support Scientific Medical Advisor relationship with United Therapeutics Please note: $1001 - $5000 Added 04/22/2020 by Oksana Shlobin, source=Web Response, value=Consulting fee

ASSOCIATION OF DONOR ALLOCATION SEQUENCE WITH OUTCOMES AFTER LUNG TRANSPLANTATION

SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: There is limited data regarding the association of donor allocation sequence number with early complications such as primary graft dysfunction (PGD) and survival after lung transplantation (LT). METHODS: We included 152 consecutive patients who underwent LT over a two-year period (11/2014-12/2016; mean age 56.8±13.2 years; M:F 93:59). The data regarding the allocation characteristics as well as graft survival were obtained directly from the United Network for Organ Sharing (UNOS) database. This data was merged with the institutional recipient database. Recipient data included baseline characteristics, peri-operative and post-operative course, complications and hospital outcomes. Primary graft dysfunction was analyzed as the primary outcome variable whereas the hospital length of stay and survival at one, and three-year post transplant were secondary outcome variables. RESULTS: The most common diagnostic group was restrictive lung diseases (n=81, 52.2%) with a mean lung allocation score (LAS) of 44.8±15 and majority underwent bilateral LT (n=98). The median allocation sequence was 4.5 for the study group (IQR 2-13). The study group was divided into patients who were transplanted at sequence #1 (n=29) vs those transplanted with organs accepted at lower allocation sequence. Patients with higher mean LAS (56.4±19.5 vs 42.1±12.4, p<0.001), restrictive disorders as the transplant indication (72% vs 48.7%, p=0.03), hospitalized at the time of LT (28% vs 9%, p=0.06) and bridged to LT using ECMO (21% vs 3%, p=0.001) were significantly more likely to be transplanted at sequence #1. Despite being sicker, recipients of allocation sequence #1 had significantly lower incidence of PGD 2 or 3 at 0 hours (24%, vs 61%, p<0.001; mean PF ratio: 357±81 vs 273±107, p<0.001) and 72 hours (14% vs 28%, p=0.15 mean PF ratio: 303±147 vs 198±167, p=0.002). Although, the recipients of allocation at sequence #1 experienced equivalent hospital survival, their survival trended lower at one-year and three-year follow up (p=NS). CONCLUSIONS: While patients transplanted at allocation sequence #1 tend to be sicker, they have better oxygenation during the first 72 hours after LT and lower risk of PGD. Nonetheless, a higher donor allocation sequence is not associated with superior one-year or three-year survival. CLINICAL IMPLICATIONS: By virtue of being prioritized for LT, sicker recipients may be transplanted with better quality donor lungs. While this allocation strategy may be successful in reducing early complications, it fails to improve post-LT survival. DISCLOSURES: My spouse/partner as a Employee relationship with Abbott Labs Please note: $20001 - $100000 Added 06/05/2020 by Amit Banga, source=Web Response, value=Salary No relevant relationships by SRINIVAS Bollineni, source=Web Response No relevant relationships by John Joerns, source=Web Response No relevant relationships by Vaidehi Kaza, source=Web Response No relevant relationships by Adrian Lawrence, source=Admin input No relevant relationships by Manish Mohanka, source=Web Response No relevant relationships by John Murala, source=Web Response No relevant relationships by Matthias Peltz, source=Web Response No relevant relationships by Lauren Shaffer, source=Web Response No relevant relationships by Fernando Torres, source=Web Response No relevant relationships by Michael Wait, source=Web Response

A Novel Risk Scoring System for Predicting Primary Graft Dysfunction after Orthotopic Heart Transplantation

Introduction Despite advances in graft survival following orthotopic heart transplantation (OHT), primary graft dysfunction (PGD) remains a major problem. PGD - defined as ventricular dysfunction occurring within 24 hours after OHT not associated with a discernible cause - is the leading cause of death in the first 30 days post OHT. The etiology of PGD is multifactorial including donor age, recipient inotropic support and amiodarone use. Hypothesis We would be able to identify novel donor and recipient factors associated with increased incidence of PGD. Methods We analyzed patients undergoing OHT from January 2014 to December 2019. Patients without 1-year follow up data were excluded. PGD was diagnosed based on the 2013 ISHLT consensus definition. Donor and recipient characteristics were analyzed using chi-square or Fisher exact test as appropriate, 2-tailed, with p Results 122/143 OHT recipients had 1 year followup. PGD occurred in 36 (29.5%) patients. Patient proportions with donor-recipient height mismatch>20% (0 vs 0), weight mismatch>20% (34% vs 42%, p=0.32), and sex mismatch (13.8% vs 10.5%, p=0.76) were similar for PGD and non-PGD groups. Independent predictors of PGD were donor pH 50% (OR 13.85, 95%CI 3.3-58, p=0.01). Based on beta coefficients in the regression model, we allotted 1 point to milrinone use, 2 to amiodarone use, and 3 points each to donor pH 50%. The derived risk score demonstrated a powerful association with PGD occurrence (per point increase OR 2.0; p Conclusion We identified novel factors associated with the development of PGD, including recipient milrinone use and elevated class 2 PRA, while confirming prior well-validated risk factors such as amiodarone use and donor acidemia. A PGD risk score incorporating these factors powerfully predicts PGD occurrence, and may assist in future donor utilization and identification of recipients at risk for PGD.

A single-center long-term experience with marginal donor utilization for heart transplantation.

To evaluate the early and late outcome of heart transplantation (HT) using marginal (MDs) and optimal donors (ODs). Clinical records of recipients transplanted between July 2004 and December 2014 were retrospectively reviewed. MDs were defined as follows: age >55years, high-dose inotropic support, left ventricular ejection fraction <45%, left ventricular hypertrophy, donor to recipient predicted heart mass ratio <0.86, ischemic time >4hours. A total of 412 (55%) recipients received an organ from a MD; recipients who received an organ from an OD had less primary graft dysfunction (PGD) (25% vs 38%; P<.001), less acute renal failure (23% vs 34%; P<.001), and higher survival rates (90.2% vs 81.8% at 30days, 79.5% vs 71.1% at 1year, 51.8% vs 45.4% at 12years; P=.01) than recipients who received an organ from a MD. There was no statistically significant difference in 30-day conditional survival between the two groups (survival rates 57.4% vs 55.5% at 12years; P=.43). PGD, perioperative hemodialysis, and sepsis were independent risk factors of mortality at multivariate analysis. Utilization of MDs for HT is associated with a higher incidence of PGD and acute renal failure, and a reduction of 30-day survival.

Strategic application of modular risk components to safely increase lung transplantation volume.

Considerable growth of individual lung transplant programs remains challenging. We hypothesized that the systematic implementation of modular risk components to a lung transplantation program would allow for expeditious growth without increasing mortality. All consecutive patients placed on the lung transplantation waitlist were reviewed. Patients were stratified by an 18-month period surrounding the systematic implementation of the modular risk components Era 1 (1/2014-6/2015) and Era 2 (7/2015-12/2016). Modular risk components were separately evaluated for donors, recipients, and perioperative features. One hundred and thirty-two waitlist patients (Era 1: 48 and Era 2: 84) and 100 transplants (Era 1: 32 and Era 2: 68) were identified. There was a trend toward decreased waitlist mortality (P = .07). In Era 2, the use of ex vivo lung perfusion (P = .05) and donor-recipient over-sizing (P = .005) significantly increased. Moreover, transplantation with a lung allocation score greater than 70 (P = .05), extracorporeal support (P = .06), and desensitization (P = .008) were more common. Transplant rate significantly improved from Era 1 to Era 2 (325 vs 535 transplants per 100 patient years, P = .02). While primary graft dysfunction (PGD) grade 3 at 72 hours (P = .05) was significantly higher in Era 2, 1-year freedom from rejection was similar (86% vs 90%, P = .69) and survival (81% vs 95%, P = .02) was significantly greater in Era 2. The systematic implementation of a modular risk components to a lung transplantation program can result in a significant increase in center volume. However, measures to mitigate an expected increase in the incidence of PGD must be undertaken to maintain excellent short and midterm outcomes.

A Direct Comparison Between Institut Georges Lopez 1 and Histidine-Tryptophan-Ketoglutarate Preservation Solutions in Liver Transplantation

BackgroundThe Institut Georges Lopez 1 (IGL-1) solution was developed to improve the outcomes of solid organ transplantation. Nevertheless, follow-up of liver transplants using IGL-1-preserved organs is still scarce. AimTo compare morbidity, postoperative complications, and early survival between liver grafts perfused with IGL-1 and those perfused with histidine-tryptophan-ketoglutarate (HTK) solutions. MethodsProspective liver grafts perfused with IGL-1 (n = 65) were paired with a historical control group of recipients whose grafts were preserved with HTK solution (n = 130). The primary endpoint was the sum of the incidence of primary graft dysfunction (PGD) and primary graft nonfunction (PGNF). Secondary endpoints included resource utilization, complications, and survival analysis. ResultsIn the HTK group, 52 patients (40%) exhibited either PGD or PGNF, compared to 20 patients (31%) in the IGL-1 group (P = .208). Patients from the HTK group had higher mean values for cryoprecipitate transfusion (P = .0064), first day serum lactate (P = .0099), higher incidence of vascular complications (11% vs 2% in the IGL-1 group; P = .0226), but a lower incidence of infection (7% vs 28% in the IGL-1 group; P < .0001). The IGL-1 group presented a lower mean aspartate aminotransferase and alanine aminotransferase (ALT) on the first and second postoperative day and a lower ALT on the seventh day. Recipients of grafts perfused with IGL-1 had a better early survival than those whose grafts were perfused with HTK. ConclusionsBoth solutions are safe and present good results. Grafts perfused with IGL-1 showed decreased enzymatic peaks and better short-term survival rates than the HTK group. The use of the IGL-1 solution might be preferable.

Right Heart Failure While on Left Ventricular Assist Device Support Is Associated with Primary Graft Dysfunction.

Primary graft dysfunction (PGD) is a potentially devastating complication of heart transplantation. Understanding the risk factors for PGD in the modern era of heart transplantation is of vital importance. This study investigated the relationship between post-left ventricular assist device (LVAD) right heart failure (RHF) and transplant outcomes. Patients with durable, continuous-flow LVADs who were transplanted between 2010 and 2016 at Barnes-Jewish Hospital were included in the study. Data collection was performed through retrospective chart review. The primary outcome was the incidence of PGD stratified by pretransplant incidence of RHF while on LVAD support. Among the 141 patients included in the study, 41 developed RHF. In the RHF cohort, 18 patients developed PGD as compared to 14 patients in the group without RHF (44% vs. 14%; p < 0.001). Mortality was significantly higher in the RHF group at 30 days (20% vs. 1%; p < 0.001) and 1 year (22% vs. 6%; p = 0.013). In a multivariable logistic regression model adjusted for confounding variables, RHF was associated with a nearly fourfold increased risk of PGD (odds ratio, 3.91; p = 0.003). The results of this study show that patients supported with LVADs who develop early severe RHF or late RHF are at increased risk of PGD and death following cardiac transplantation.

Effect of Cold Ischemic Time on the Incidence of High-Grade Primary Graft Dysfunction (PGD): A Multicenter Analysis

Prior studies have explored the effects of cold ischemic time on survival but its effect on PGD is unclear. The current study analyzed an international multicenter ECLS in lung transplantation registry to clarify the effects of cold ischemic time on PGD. The ECLS in lung transplantation registry includes data on bilateral lung transplants from 8 high volume (>40 transplants/yr) transplant centers (2 from Europe, 6 from United States). This registry excludes single lung transplants and multi-organ transplants and the current analysis excluded Ex Vivo Lung Perfusion (EVLP) cases. We defined primary graft dysfunction according to the 2016 ISHLT consensus document and considered PGD3 at time 48 or 72 hours as high-grade primary graft dysfunction (PGD). We defined cold ischemic time as the interval between donor cross clamp (cardiac arrest for donation after circulatory death cases) and the longest reperfusion time in the recipient. We explored the effect of the cold ischemic time on PGD and death within 90 days using univariate and multivariate logistic regression analysis. We identified 511 entries with complete ischemic times between January 2016 and August of 2019. The overall incidence of PGD was 30.7%. The mean cold ischemic time in the group that developed PGD was 406 minutes and 428 minutes in the group that did not develop PGD. Univariate regression analysis showed no effect of ischemic time on the incidence of PGD (P=0.12). ROC analysis yielded an area under the curve for cold ischemic time and PGD of 0.55 further suggesting that cold ischemic time was poorly predictive of PGD. Our adjusted analysis showed no effect of total ischemic time on PGD (P=0.75). Finally, both univariate and multivariate analysis failed to show significance for the effect of total ischemic time on death within 90 days (P=0.33 and P=0.54, respectively). In a large multicenter registry, we could not identify an effect of duration of cold ischemic time on incidence of PGD or 90-day mortality. Practitioners should avoid using cold ischemic times in isolation to accept or decline a potential organ, although its effects on early reperfusion and long-term graft function require further study as does the extent of tolerable cold ischemia.

Effect of Time of Intraoperative Circulatory Support on Incidence of High-Grade Primary Graft Dysfunction (PGD): Multicenter Analysis on Use of Extracorporeal Life Support (ECLS) during Lung Transplantation

Prior single center experiences suggest that use of ECLS during lung transplantation (LT) increases the risk of PGD. Here we analyze the effects of intraoperative ECLS time on PGD after LT in a multicenter ECLS registry. The ECLS in LT registry includes data on bilateral LTs from 8 centers (2 from Europe, 6 from United States). The registry excludes single lung transplants and multi-organ transplants and defines primary graft dysfunction according to the ISHLT 2016 consensus statement. Herein, we refer to PGD as a single case developing PGD3 at time 48 and/or 72 hours. We explored the risk of intraoperative ECLS time on the incidence of PGD and death within 90 days using adjusted and unadjusted logistic regression and receiver operating curve (ROC) analysis. We identified 297 ECLS patients with intraoperative support times available between January 2016 and August of 2019. Breakdown of cases were as follows: 44% CPB, 66% ECMO (16% VV, 64%VA/VVA, 20% modified bypass-VA). Out of these, 35.6% developed PGD and 6% died within 90 days. Median time of ECLS support was 206 minutes (62-686 minutes). The median time of support was 200 minutes in patients without PGD and 206 minutes in cases with PGD. The median time of support was 202 minutes in patients who survived 90 days compared to 271 minutes in patients who did not survive 90 days. Our unadjusted and adjusted logistic regression analysis showed that time of ECLS was not associated with PGD irrespective of the mode of ECLS (CPB v ECMO). In addition, ROC analysis showed an area under the curve for ECLS time of 0.51 suggesting poor predictability for PGD. Our unadjusted analysis showed that increased time on ECLS was significantly associated with death within 90 days (P=0.014) although this was of borderline significance after adjusting for risk factors (P=0.067). Furthermore, this effect was of borderline significance for CPB (P=0.07) and not significant for ECMO (P=0.17). In an international multicenter registry on use of ECLS in LT, the time on ECLS did not alter the risk of PGD with either CPB or ECMO, although it was associated with perioperative death. Surgeons should limit the time spent on ECLS when feasible and consider ECMO for longer procedures.

Impact of Histidine-Tryptophan-Ketoglutarate Preservation Solution in Heart Transplantation with Extended Distance

In countries with such continental dimensions, and low rates of organs donations and recovery, strategies to shorten the waiting time in heart transplantation (HT) list are still required. A prolonged ischemic time (pISQT, >240 min) has been reported to be a significant factor leading to primary graft dysfunction (PGD). Thus, optimal heart preservation is mandatory for transplant procedures with pISQT. Use of Histidine-Tryptophan-Ketoglutarate (HTK) solution has been suggested to improve extended organ preservations up to 180 min. This study investigated the impact of the donor distance (DD) from transplantation center and pISQT on PGD after HT using preservation with HTK solution. Between January 2017 and December 2018, all 92 consecutive patients underwent HT at our institution after preservation with HTK solution were retrospectively evaluated divided into 2 groups according to the DD: (G1) 46 patients underwent HT with a DD <100km, and (G2) 46 patients after HT with a DD >100km. No significant differences were observed with regard to gender, age, diagnosis, donor inotropic support, and donor-recipient weight ratio among patients in G2 when compared with G1. The PGD was characterized using the ISHLT defined criteria. Descriptive analyses of the results are presented as mean values and standard deviations. The analytical studies were performed with the Fisher exact test. Kaplan-Meier and log-rank tests were performed to investigate survivals. All analyses were performed using R and p<0.05 was considered to be significant. The incidence of PGD was similar in both groups (p=0.81). After risk adjustment, longer DD were associated with a significantly lower risk of mortality at both 60 days (p=0.05, Figure 1). This study illustrates that HTK solution may help to expand donor acceptance criteria to include more distant donor heart locations and accepting longer allograft ischemic times without increase in PGD and mortality after transplantation.

Does the Pretransplant Use of Statins in Recipients Have a Role in the Incidence of Primary Graft Dysfunction after Lung Transplantation? R-ESTAcitos: Multicenter Clinical Study

Primary graft dysfunction (PGD) is the main cause of mortality during the first month and the second one within the first year after lung transplant (LT) Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have shown to have immunomodulatory and antiinflamatory effects unrelated to their cholesterol-lowering function. We hypothesized that recipient's preoperative statin therapy is associated with decreased incidence of PGD after LT. Multicenter retrospective analysis of all consecutive adult LTs performed in 5 university transplant centers between 2015 and 2017. Combined multiple organ transplantation and lung retransplant recipients were excluded from the analysis. Comparison between groups according to recipient previous use of statins(E+/E-)) was performed. Factors associated with the development of PGD and its severity were analyzed using Chisquare and U-Mann Whitney Test. Logistic regression model was built including those variables with p≤0.1 in the univariate analysis. Significance level p<0.05. A total of 474 adult LT recipients were reviewed, 110 of them (E+=23%) were on statins treatment (SG). LT recipients in the statin group were older (60±7 vs 53±12; p<0.05) and had higher Body Mass Index (BMI) (26.3±3.8 vs 24.8±4.2;p<0.05) than those in not taking statins. The rest of recipient and donor characteristics were similar between groups. A total of 161 patients developed PGD (34%), without significative differences between groups (32.2% vs 39%). However PGD in E+ group was significantly less severe as stated by the percentage of patients with grade 3 PGD at 72h (55.9% vs 37.2%,p<0.036). After propensity score adjustments, only the need for hemoderivates transfusion during the implant (OR 4.50 IC 1.51 - 13.38 p<0.007) remained significant. Recipient statin use was not identified as a protective factor (OR 0.38 CI 0.12 - 1.206, p=0.10). Statin use may contribute to lessen the severity of PGD. Prospective and multicentric studies with larger samples are needed to confirm such results.

Spontaneous Restoration of Sinus Rhythm during Heart Transplantation is Associated with a Reduced Incidence of Primary Graft Dysfunction and Early Mortality

Insults to the donor heart during heart transplantation (HT) include ischemia and reperfusion injury after release of the aortic cross-clamp in the recipient. Restoration of heart beat after aortic unclamping can be by spontaneous resumption of sinus rhythm, pacing for atrioventricular (AV) block, or direct-current (DC) cardioversion for ventricular fibrillation. We investigated the association between mode of heart beat restoration and primary graft dysfunction (PGD). HT recipients between 1997-2017 were grouped by mode of heart beat restoration after aortic unclamping into: spontaneous (S; 126 pts), pacing (P; 17 pts) or DC (58 pts) groups. Endpoints were 30-day mortality and PGD (defined by the ISHLT consensus statement). Baseline characteristics differing among the groups included proportion of women, pre-HT amiodarone and gender mismatch (Table). PGD was significantly higher for the P-group (71%) >DC-group (59%) >S-group (21%, p<0.001). Multivariable analysis consistently showed that restoration of sinus by DC, and pacing for AV block, were independently associated with significant ∼5-fold and ∼10-fold increased risk for PGD, respectively (Figure) compared to spontaneous sinus restoration. Consistently, 30-day mortality was significantly lower for S- (6%) than for DC- (17%) patients and highest for the P group (22%, p<0.001). Spontaneous restoration of sinus after aortic unclamping at HT is associated with a reduced risk for PGD and early mortality, whereas pacing for AV block and DC are associated with an increased risk.

Use of Cardiac Grafts from Suicidal Hanging Donors: Single-Center Experience

Donors of death due to anoxic brain injury such as suicidal hanging are at risk for a severe catecholamine surge leading to an acute myocardial stress that can cause global tissue hypoxia as well as pulmonary edema and barotrauma, all of which may potentially adversely impact myocardial tissue. Concerns have been raised about potential higher rates of Primary Graft Dysfunction (PGD) in heart transplant recipients of such donors due to this acute myocardial stressor. We wanted to assess if this mechanism of donor death does carry an increased risk of PGD or other adverse outcomes in our single center experience. Between January 2014 and July 2019, 331 heart transplantations were performed at our center. Seventeen patients received a heart from donors after suicidal hanging, confirmed by review of the United Network for Organ Sharing UNet DonorNet database. Three out of 17 recipients (18%) from suicidal hanging donors experienced primary graft dysfunction (PGD) peri-operatively requiring extracorporeal membrane oxygenation (ECMO). In comparison, 29 out of 314 recipients (9%) from all other donors during this time period experienced PGD requiring peri-operative ECMO (p = 0.25). The 30-day and 1-year survival among recipients of grafts from suicidal hanging donors were 16/17 (94%) and 16/17 (94%), respectively. The one death during this period was due to complications from PGD (multi-system organ failure, ischemic limb with ECMO). Overall, in a large-volume, single-center experience, while there was a trend toward a higher incidence of PGD requiring ECMO, transplantation of a heart from a suicidal hanging donor was not associated with a higher 30-day and 1-year mortality. Thus, these results suggest that hearts from suicidal hanging donors may be appropriately considered for transplantations, with heightened awareness of a possible increased risk of PGD requiring ECMO.

Preoperative Statin Therapy and Heart Transplantation Outcomes

Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality after heart transplantation (HT). Statins are known to have immunomodulatory and antiinflammatory effects, and perioperative statin therapy has been associated with reduced cardiovascular complications and improved outcomes after cardiac and noncardiac surgery. Thus, we investigated the influence on PGD of statin therapy administered to recipients before HT. A retrospective cohort study was conducted on 275 HT recipients assessed from 1997 to 2017; 167 (61%) had received statins during the month prior to and at time of transplantation, whereas 108 (39%) had not. Endpoints included PGD (defined according to the International Society of Heart and Lung Transplantation consensus statement), in-hospital mortality, and 1-year and 5-year survival. PGD incidence was significantly lower for statin-treated patients (21 vs 60%, P < .001). Multivariable analysis demonstrated that pre-HT statin therapy was independently associated with a significant 65% reduced risk for PGD and a 73% reduced risk for in-hospital mortality. One- and five-year mortality, adjusted for age, sex, and amiodarone therapy, were significantly lower for recipients treated with statins (hazard ratio 0.33 and 0.39, 95% confidence interval 0.17-0.63 and 0.22-0.68, respectively; P= .001). Pre-HT statin therapy was independently associated with a reduced risk for PGD and mortality. Our results also suggested that statins have a beneficial prognostic impact on heart failure patients awaiting HT.

Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction.

Recent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD. This was a single-center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3). 53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P<.001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26-10.88; P=.018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR=0.416, 95% CI=0.08-2.15; P=.296). We found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.

Comparison of outcomes in lung and heart transplant recipients from the same multiorgan donor.

Primary graft dysfunction (PGD) and acute cellular rejection (ACR) are important causes of early morbidity and mortality following lung and heart transplantation. While many studies have elucidated donor-related risk factors of PGD and ACR, these complications often occur even with "ideal" donors. Therefore, we investigated potential associations of PGD and ACR between bilateral lung and heart transplant recipients from the same multiorgan donor, respectively. Between 2011 and 2017, 100 donors contributed 100 bilateral lung transplants and 100 heart transplants performed. Logistic regression analysis for PGD and Cox proportional hazards regression analysis for ACR were used to estimate the relationship of heart and lung transplants. The incidence of PGD was 33% among lung and 17% among heart transplant recipients. Similarly, the incidence of ACR grade≥A2 for lung recipients was 38% (30/80), and the incidence of ACR grade≥2R for heart recipients was 19% (15/80). There was no association between the development of PGD and ACR in lung and heart transplant recipients from the same donor, respectively. These findings suggest that inherent donor factors are not critical to the development of PGD and ACR after lung and heart transplantation.

The Conversional Efficacy of Ex Vivo Lung Perfusion and Clinical Outcomes in Patients Undergoing Transplantation of Donor Lungs by Ex Vivo Lung Perfusion: A Meta-Analysis.

BackgroundEx vivo lung perfusion (EVLP) is a relatively new technique that can be used to assess and repair the donor lungs, increasing the utilization of high-risk lungs. However, its effect on outcomes of lung transplantation patients is uncertainty. This meta-analysis is conducted to assess the impact of EVLP on donor lungs and outcomes of recipients compared with the standard lung transplantation.Material/MethodsWe systematically searched for studies comparatively analyzing the efficacy of EVLP and standard cold storage in lung transplantation. The hazard ratio (HR), relative risk (RR), and weighted mean difference (WMD) were used as the effect size (ES) to evaluate the survival outcomes, categorical variables, and continuous variables respectively.ResultsA total of 20 published articles (including 2574 donors and 2567 recipients) were eligible. The chest x-ray manifestations and PaO2/FiO2 100% were more deficient in the EVLP group than the standard group. EVLP improved the function of high-risk donor lungs with the conversion rate ranging from 34% to 100%. The EVLP group had a lower incidence of primary graft dysfunction 3, but longer intensive care unit stay. Other clinical outcomes between the 2 groups were similar.ConclusionsThe pooled results indicated that EVLP could be used to assess and improve high-risk donor lungs and had non-inferior postoperative outcomes compared with the standard cold storage. EVLP not only increased the utilization of marginal donors, but also could extend preservation time and reduce the total ischemia time of donors.