Severe Primary Graft Dysfunction Research Articles

Increased Donor Organ Size and Age is Associated with Reduced Survival in Female Lung Transplant Recipients

BackgroundOrgan selection in lung transplantation (LTx) is still controversial. We here analyze the impact of mismatches in size, age, and gender on early and long-term outcome after LTx. MethodsRetrospective analysis of donor and recipient characteristics of patients who underwent double lung transplantation (DLTx) between 03/2003 and 12/2021. Statistical analysis was performed using SPSS and GraphPad software. Results203 patients were included (94 female and 109 male). In the whole cohort, oversizing donor organs 10%-20% compared to the recipients’ predicted total lung capacity (pTLC) led to a decreased incidence of severe primary graft dysfunction (PGD2/3) (15% vs. 41%, p=0.03), and further oversizing >20% was associated with reduced long-term survival (HR 2.33, p=0.011). Analysing donor and recipient age, we found that increased donor age correlated with reduced long-term survival (p=0.013). In this cohort, female recipients received older organs (median 57 vs. 46 years, p=0.0003) and had a higher incidence of >20% oversizing (13% vs. 4%, p=0.019) of donor lungs which resulted in a significantly reduced long-term survival (p=0.02) compared to male recipients. Median LAS scores were similar in both groups. ConclusionMismatch of donor age and size can be important for organ function and survival in lung transplant recipients. Particularly female recipients seem to have a higher risk for unfavourable long-term outcome when transplanting organs of increased size and age. Multicentre studies are warranted to further address this question.

The Impact of Ipsilateral Implantable Cardioverter Defibrillator in Axillary Intra-Aortic Balloon Pump Support as Bridge to Heart Transplantation.

The axillary artery (AX) access for intra-aortic balloon pump (IABP) as a bridge to heart transplant (HT) allows mobility while awaiting a suitable donor. As end-stage heart failure patients often have an implantable cardioverter defibrillator (ICD) on the left side, the left AX approach may be avoided due to the perception of difficult access and proximity of two devices. We aimed to evaluate the outcomes of patients bridged to HT with a left-sided AX IABP with or without ipsilateral ICDs. We retrospectively reviewed HT candidates at our institution supported by left-sided axillary IABP from November 2019 to February 2024, dividing them into two groups based on the presence (Group ICD, n = 48) or absence (Group No-ICD, N = 19) of an ipsilateral left-sided ICD. The exposure time was defined as the time from skin incision to the beginning of anastomoses of a Dacron graft. Technical success was achieved in 100% of the cohort, with median exposure times for AX access similar between groups (ICD, 12 [7.8, 18.2] vs. No ICD, 11 [7, 19] min; p = 0.75). The rate of procedural adverse events, such as significant access site bleeding and ipsilateral limb ischemia, did not significantly differ between both groups. Device malfunction rates were comparable (ICD, 29.2%vs. No ICD, 15.8%; p = 0.35). Posttransplant, in-hospital mortality, severe primary graft dysfunction, and stroke rates were comparable in both groups. The presence of an ipsilateral left-sided ICD does not adversely impact the procedural efficacy, complication rates, or posttransplant outcomes of left-sided AX IABP insertion in HT candidates.

Impact of Pre-Transplant Left Ventricular Diastolic Pressure on Primary Graft Dysfunction after Lung Transplantation: A Narrative Review.

Lung transplantation (LT) constitutes the last therapeutic option for selected patients with end-stage respiratory disease. Primary graft dysfunction (PGD) is a form of severe lung injury, occurring in the first 72 h following LT and constitutes the most common cause of early death after LT. The presence of pulmonary hypertension (PH) has been reported to favor PGD development, with a negative impact on patients' outcomes while complicating medical management. Although several studies have suggested a potential association between pre-LT left ventricular diastolic dysfunction (LVDD) and PGD occurrence, the underlying mechanisms of such an association remain elusive. Importantly, the heterogeneity of the study protocols and the various inclusion criteria used to define the diastolic dysfunction in those patients prevents solid conclusions from being drawn. In this review, we aim at summarizing PGD mechanisms, risk factors, and diagnostic criteria, with a further focus on the interplay between LVDD and PGD development. Finally, we explore the predictive value of several diastolic dysfunction diagnostic parameters to predict PGD occurrence and severity.

Early serum biomarkers to characterise different phenotypes of primary graft dysfunction after lung transplantation: a systematic scoping review.

Lung transplantation (LUTX) is often complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping. Following JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following International Society for Heart and Lung Transplantation (ISHLT) guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases. Among the 1050 papers screened, 25 prospective observational studies were included, with only nine conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44-119)). Most (n=21) compared PGD grade 3 to less severe PGD, but only four adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and two papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, three endothelial activation, three epithelial injury, three cellular damage and two coagulation dysregulation markers. Only five biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent area under the receiver operating characteristic curve analysis, yielding a median value of 0.58 (0.51-0.78) in 406 patients (276 double LUTX). Several biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms and advanced statistical approaches are essential.

Impact of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplant Outcomes.

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are acute, significant respiratory deteriorations in patients with IPF and can lead to increased morbidity and mortality. It remains unclear how AE-IPF impacts lung transplant (LTX) outcomes. All adult patients who were listed for LTX between July 2005 and October 2020 at the Loyola University Medical Center with a diagnosis of IPF were included. Pretransplant characteristics and posttransplant outcomes were gathered via retrospective chart review. The primary outcome was short- and long-term survival for patients transplanted during stable IPF versus those with AE-IPF. One hundred fifty-nine patients were included in this study, 17.6% of whom were transplanted during AE-IPF. AE-IPF patients were more likely to have higher oxygen needs pretransplant, have higher lung allocation score, and were more likely to be intubated or be on extracorporeal membrane oxygenation as compared with stable IPF patients. Survival by AE status at transplant did not differ at 90 d or 1 y posttransplantation. There were also no significant differences in rates of severe primary graft dysfunction or acute rejection within 1 y. Patients with AE-IPF were more likely to have higher oxygenation requirements and higher lung allocation score at the time of LTX than those with stable IPF. Despite this, there were no differences in survival at 90 d, 1 y, or 3 y, or differences in incidence of severe primary graft dysfunction or acute cellular rejection. Transplantation of patients with AE-IPF has clinical outcomes comparable with transplantation of patients with stable IPF. This contrasts with previous studies examining LTX in patients with AE-IPF.

Body mass index and mortality following primary graft dysfunction: A Lung Transplant Outcomes Group study

Higher body mass index (BMI) increases risk of developing primary graft dysfunction (PGD) after lung transplantation; whether BMI is associated with decreased survival after PGD is unknown. We utilized the Lung Transplant Outcomes Group (LTOG) cohort of 1,538 subjects from 2011-2018. We evaluated the association between pre-operative BMI and graft survival among subjects with severe PGD using Cox proportional hazards models with linear splines. Models were stratified by center and adjusted for sex, age, lung allocation score, and diagnosis. PGD developed in 383 subjects. Among subjects with PGD, low BMI was associated with increased mortality while high BMI was not associated with differential mortality, compared to normal BMI. Results were similar for 90-day and 1-year survival. While high BMI increases risk of developing PGD, it does not appear to be associated with survival after PGD. Future work should focus on PGD prevention rather than PGD management in patients with obesity.

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.

(285) - Sex Based Differences in Severe Primary Graft Dysfunction: An Analysis from the International Consortium on PGD

(285) - Sex Based Differences in Severe Primary Graft Dysfunction: An Analysis from the International Consortium on PGD

(772) - Incidence of Moderate and Severe Primary Graft Dysfunction in DBD vs. DCD Heart Transplantation in Patients with Pre-Existing Durable LVAD Support

(772) - Incidence of Moderate and Severe Primary Graft Dysfunction in DBD vs. DCD Heart Transplantation in Patients with Pre-Existing Durable LVAD Support

(326) - Impact of the 2018 UNOS Allocation Change on Severe Primary Graft Dysfunction: A Report from the International Consortium on PGD

(326) - Impact of the 2018 UNOS Allocation Change on Severe Primary Graft Dysfunction: A Report from the International Consortium on PGD

(917) - The Presence of Cold Agglutinins in Recipients is a Risk Factor for Severe Primary Graft Dysfunction After Lung Transplantation

(917) - The Presence of Cold Agglutinins in Recipients is a Risk Factor for Severe Primary Graft Dysfunction After Lung Transplantation

(270) - Defining the Transcripts Associated with a History of Severe Primary Graft Dysfunction in Lung Transplant Transbronchial Biopsies

(270) - Defining the Transcripts Associated with a History of Severe Primary Graft Dysfunction in Lung Transplant Transbronchial Biopsies

(770) - Comparative Regional Analysis of Severe Primary Graft Dysfunction: Insights from Tthe International Consortium on PGD

(770) - Comparative Regional Analysis of Severe Primary Graft Dysfunction: Insights from Tthe International Consortium on PGD

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.

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial

ObjectiveDonation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. MethodsThis was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. ResultsThe DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. ConclusionsAlthough DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Preoperative Amiodarone and Primary Graft Dysfunction in Heart Transplantation.

Preoperative amiodarone effects on postorthotopic heart transplant (OHT) outcomes remain controversial. The purpose of this study was to determine the effect of cumulative pre-OHT amiodarone exposure on severe primary graft dysfunction (PGD). We retrospectively reviewed adult OHT recipients between August 2012 and June 2018. Primary outcome was severe PGD in patients receiving amiodarone at 3, 6, and 12 months prior to OHT compared with those not receiving amiodarone. Secondary outcomes included intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, early graft failure (EGF), mortality at 3, 6, and 12 months post-OHT, and 30-day incidence of postoperative tachyarrhythmias, bradycardia, permanent pacemaker implantation, and rejection. Incidence of severe PGD was 12.5% in those who received amiodarone compared to 6.8% in those who did not (14 vs 6, P = 0.18). Cumulative preoperative amiodarone significantly increased the odds of severe PGD at 3 months (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.001-1.06; P = 0.044) and 6 months (OR: 1.02, 95% CI: 1.003-1.044; P = 0.024) in a multivariate logistic regression. Patients on amiodarone had significantly higher rates of postoperative bradycardia (13.4% vs 4.5%, P = 0.03). A trend toward increased PGD was present in patients receiving preoperative amiodarone. This finding combined with the regression showing significantly increased odds of PGD with increasing 3 and 6 month cumulative amiodarone dose is clinically concerning. Escalation of care with pacemaker implantation was required more frequently in patients on pre-OHT amiodarone.

Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation.

Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml. Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction.

Outcomes in Heart Transplant Recipients by Bridge to Transplant Strategy When Using the SherpaPak Cardiac Transport System.

The last several years have seen a rise in use of mechanical circulatory support (MCS) to bridge heart transplant recipients. A controlled hypothermic organ preservation system, the SherpaPak Cardiac Transport System (SCTS), was introduced in 2018 and has grown in utilization with reports of improved posttransplant outcomes. The Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN)-Heart registry is an international, multicenter registry assessing outcomes after transplant using the SCTS. This analysis examines outcomes in recipients bridged with various MCS devices in the GUARDIAN-Heart Registry. A total of 422 recipients with donor hearts transported using SCTS were included and identified. Durable ventricular assist devices (VADs) were used exclusively in 179 recipients, temporary VADs or intra-aortic balloon pump (IABP) in 197, and extracorporeal membrane oxygenation (ECMO) in 14 recipients. Average ischemic times were over 3.5 hours in all cohorts. Severe primary graft dysfunction (PGD) posttransplant increased across groups (4.5% VAD, 5.1% temporary support, 21.4% ECMO), whereas intensive care unit (ICU) length of stay (18.2 days) and total hospital stay (39.4 days) was longer in the ECMO cohort than the VAD and IABP groups. A comparison of outcomes of MCS bridging in SCTS versus traditional ice revealed significantly lower rates of both moderate/severe right ventricular (RV) dysfunction and severe PGD in the SCTS cohort; however, upon propensity matching only the reductions in moderate/severe RV dysfunction were statistically significant. Use of SCTS in transplant recipients with various bridging strategies results in excellent outcomes.

Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial

BackgroundExtended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. ObjectivesThis study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. MethodsIn this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft–related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. ResultsA total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft–related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. ConclusionsUse of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754)

Development of an experimental technique for orthotopic left lung transplantation in a rabbit model

Objective: to develop, master and evaluate the efficiency of an isolated lung transplantation (LT) technique on a rabbit animal model using Perfadex Plus® solution for cold static storage. Materials and methods. Scottish Giant rabbits (n = 20) were used in this study and divided into two groups: donors and recipients. Donor lungs were preserved with Perfadex Plus® solution and stored for 6 hours at 4 °C. Recipient animals underwent unilateral orthotopic left LT. The postoperative follow-up period was 24 hours. Laboratory and instrumental control with assessment of blood gas composition, lactate level, ventilation parameters, and central hemodynamic parameters, was performed during the follow-up. Chest X-ray in direct projection was performed twice, and at the end of follow-up, material was taken for histologic examination. Results. We obtained a high oxygenation index in the post-transplant period (&gt;350 at p &lt; 0.023), as well as physiological indicators of lactate (3 ± 0.3 mmol/L at p &lt; 0.002) and peak inspiratory pressure (15 ± 1 cmH2O, p &lt; 0.001). Radiological examination showed no radiological signs of severe primary graft dysfunction in all cases (mean RALE score 1), which was confirmed by histological studies. Conclusion. Left LT in rabbits is possible, the LT technique on a biological rabbit model using Perfadex Plus® solution is valid and efficient with the achievement of satisfactory gas exchange, ventilation and metabolism parameters.