Disparities in donor heart acceptance between the USA and Europe: clinical implications.

BACKGROUND AND AIMS: Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes. METHODS: Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality. RESULTS: Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually. CONCLUSIONS: Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.

The adapted Heart Donor Score.

The Heart Donor Score (HDS) predicts donor organ discard for medical reasons and survival after heart transplantation (HTX) in the Eurotransplant allocation system. Our aim was to adapt the HDS for application in the United Network for Organ Sharing (UNOS) registry. To adjust for differences between the Eurotransplant and UNOS registries, the "adapted HDS" was created (aHDS) by exclusion of the covariates "valve function," "left-ventricular hypertrophy," and exclusion of "drug abuse" from the variable "compromised history." Two datasets were analyzed to evaluate associations of the aHDS with donor organ discard (n = 70 948) and survival (n = 19 279). The aHDS was significantly associated with donor organ discard [odds ratio 2.72, 95% confidence interval (CI) 2.68-2.76, P < 0.001; c-statistic: 0.937). The score performed comparably in donors <60 and ≥60 years of age. The aHDS was a significant predictor of survival as evaluated by univariate Cox proportional hazards analysis (hazard ratio 1.04, 95% CI 1.01-1.07, P = 0.023), although the association lost significance in a multivariable model. The aHDS predicts donor organ discard. Negative effects of most aHDS components on survival are likely eliminated by highly accurate donor selection processes.

New French heart allocation system: Comparison with Eurotransplant and US allocation systems.

Graft allocation rules for heart transplantation are necessary because of the shortage of heart donors, resulting in high waitlist mortality. The Agence de la biomédecine is the agency in charge of the organ allocation system in France. Assessment of the 2004 urgency-based allocation system identified challenging limitations. A new system based on a score ranking all candidates was implemented in January 2018. In the revised system, medical urgency is defined according to candidate characteristics rather than the treatment modalities, and an interplay between urgency, donor-recipient matching, and geographic sharing was introduced. In this article, we describe in detail the new allocation system and compare these allocation rules to Eurotransplant and US allocation policies.

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant - a historical prospective study.

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2 /FiO2  ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.

Review of interactions between high-risk pediatric heart transplant recipients and marginal donors including utilization of risk score models.

BACKGROUND: Donor organ acceptance practices vary among pediatric heart transplant professionals. We sought to understand what is known about the interactions between the "high-risk" recipient and the "marginal donor," and how donor risk scores can impact this discussion. METHODS: A systematic review of published literature on pediatric HTx was undertaken with the assistance of a medical librarian. Two authors independently assessed search results, and papers were reviewed for inclusion. RESULTS: We found that there are a large number of individual factors, and clusters of factors, that have been used to label individual recipients "high-risk" and individual donors "marginal." The terms "high-risk recipient" and "marginal donor" have been used broadly in the literature making it virtually impossible to make comparisons between publications. In general, the data support that patients who could be easily agreed to be "sicker recipients" are at more risk compared to those who are clearly "healthier," albeit still "sick enough" to need transplantation. Given this variability in the literature, we were unable to define how being a "high-risk" recipient interplays with accepting a "marginal donor." Existing risk scores are described, but none were felt to adequately predict outcomes from factors available at the time of offer acceptance. CONCLUSIONS: We could not determine what makes a donor "marginal," a recipient "high-risk," or how these factors interplay within the specific recipient-donor pair to determine outcomes. Until there are better risk scores predicting outcomes at the time of organ acceptance, programs should continue to evaluate each organ and recipient individually.

Lung transplantation after allogeneic stem cell transplantation: a pan-European experience.

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT.SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed.Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001).Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.

Lung allocation score: the Eurotransplant model versus the revised US model - a cross-sectional study.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Heart re-transplantation in Eurotransplant.

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.

A retrospective database analysis to evaluate the potential of ex vivo lung perfusion to recruit declined lung donors.

Ex vivo lung perfusion (EVLP) is currently used for both standard and extended-criteria donor (ECD) lungs. To enlarge the donor pool, we might have to extend the threshold for ECD donation. The purpose of this study was to estimate how many additional ECD lungs could be recruited by EVLP. We reviewed all multi-organ donors (MODs) from our collaborative donor hospitals (January 2010-June 2015). All unused lung donors were categorized using registered donor data and evaluated by two independent investigators to identify which lungs could be transplanted after EVLP. 584 MODs were registered at our transplant center. 268 (45.9%) were declined as lung donor at the moment of registration, and 316 (54.1%) were considered as a donor for lung transplantation. In the latter, lungs from 220 (37.7%) donors were transplanted and 96 donors (16.4%) were not. We identified 78 of 364 declined donors (21.4%) whose lungs could potentially become transplantable after EVLP. With this retrospective database analysis of unused lung donors, we identified a large potential for EVLP to further increase the donor pool in transplant centers where the majority of donor lungs are already extended.

Bridging the gap in heart transplantation.

PURPOSE OF REVIEW: Countries in Europe and in the USA are proclaiming their need for an objective allocation system that can cope with distribution of a scarce resource in a changing environment of an older donor and recipient population and of an increased number of patients on mechanical circulatory support, whose prospects are increasing. RECENT FINDINGS: The current heart allocation systems in Eurotransplant, France and the USA are all urgency tier systems, where within the same tier a first-come, first-served principle is applied. Both Eurotransplant and France are developing new heart allocation schemes that hinge on a benefit principle, thereby combining the prospects of patients after transplantation with their expected clinical course while on the waiting list. In the USA, a different approach has been chosen for their new allocation scheme, as the medical urgency of the patient is the driving force behind the proposal. SUMMARY: Policies to ensure a fair, efficient, and medically optimal matching of donor organs and recipients are continually evaluated and refined. The ethical cornerstone of each organ allocation policy in the described countries is the effort of balancing justice and utility.

Childhood fever in well-child clinics: a focus group study among doctors and nurses.

BACKGROUND: Fever is common in children aged 0-4 years old and often leads to parental worries and in turn, high use of healthcare services. Educating parents may have beneficial effects on their sense of coping and fever management. Most parents receive information when their child is ill but it might be more desirable to educate parents in the setting of well-child clinics prior to their child becoming ill, in order to prepare parents for future illness management. This study aims to explore experiences of well-child clinic professionals when dealing with childhood fever and current practices of fever information provision to identify starting points for future interventions. METHODS: We held four focus group discussions based on naturalistic enquiry among 22 well-child clinic professionals. Data was analysed using the constant comparative technique. RESULTS: Well-child clinic professionals regularly received questions from parents about childhood fever and felt that parental worries were the major driving factor behind these contacts. These worries were assumed to be driven by: (1) lack of knowledge (2) experiences with fever (3) educational level and size social network (4) inconsistencies in paracetamol administration advice among healthcare professionals. Well-child clinic professionals perceive current information provision as limited and stated a need for improvement. For example, information should be consistent, easy to find and understand. CONCLUSIONS: Fever-related questions are common in well-child care and professionals perceive that most of the workload is driven by parental worries. The focus group discussions revealed a desire to optimise the current limited information provision for childhood fever. Future interventions aimed at improving information provision for fever in well-child clinics should consider parental level of knowledge, experience, educational level and social network and inconsistencies among healthcare providers. Future fever information provision should focus on improving fever management and practical skills.

Smoking Status at Time of Listing for a Heart Transplant Predicts Mortality on the Waiting List: A Multicenter Prospective Observational Study.

OBJECTIVE: We examined the association of smoking status at time of listing with waitlist mortality among heart transplant (HTx) candidates. PARTICIPANTS AND DESIGN: Data were analyzed from 316 participants (aged 53 ± 11; 18% female) of the Waiting for a New Heart Study, a prospective observational study of patients newly listed for HTx at 17 hospitals. RESULTS: During the study period (April 2005 to March 2010), 14% of those who never smoked died, 18% among former smokers died, and almost half (42%) died among those who reported smoking at time of wait listing. Multivariate Cox regression models controlling for age, sex, and disease severity revealed smoking at time of listing was associated with significantly higher risk of mortality compared to never smoking (hazard ratio [HR] = 3.43; P = .03). The relationship between smoking and mortality risk appeared to follow a dose-dependent pattern: adjusted HRs were 1.80 for those who quit ≤1 year ago, 1.25 for those who quit >1 to 10 years ago, and 0.90 for those quit >10 years ago, compared to never smokers. Smoking at time of listing may increase risk of mortality during the waiting period, indicating the need for improved strategies to achieve smoking cessation as early as possible in the course of HTx.

Pediatric heart allocation and transplantation in Eurotransplant.

Pediatric heart allocation in Eurotransplant (ET) has evolved over the past decades to better serve patients and improve utilization. Pediatric heart transplants (HT) account for 6% of the annual transplant volume in ET. Death rates on the pediatric heart transplant waiting list have decreased over the years, from 25% in 1997 to 18% in 2011. Within the first year after listing, 32% of all infants (<12 months), 20% of all children aged 1-10 years, and 15% of all children aged 11-15 years died without having received a heart transplant. Survival after transplantation improved over the years, and in almost a decade, the 1-year survival went from 83% to 89%, and the 3-year rates increased from 81% to 85%. Improved medical management of heart failure patients and the availability of mechanical support for children have significantly improved the prospects for children on the heart transplant waiting list.

Dietary habits are related to outcomes in patients with advanced heart failure awaiting heart transplantation.

BACKGROUND: Empirical evidence supporting the benefits of dietary recommendations for patients with advanced heart failure is scarce. We prospectively evaluated the relation of dietary habits to pre-transplant clinical outcomes in the multisite observational Waiting for a New Heart Study. METHODS AND RESULTS: A total of 318 heart transplant candidates (82% male, age 53 ± 11 years) completed a Food Frequency Questionnaire (foods high in salt, saturated fats, poly-/monounsaturated fats [PUFA+MUFA], fruit/vegetables/legumes, and fluid intake) at time of waitlisting. Cox proportional hazard models controlling for heart failure severity (eg, Heart Failure Survival Score, creatinine) estimated cause-specific hazard ratios (HRs) associated with each dietary habit individually, and with all dietary habits entered simultaneously. During follow-up (median 338 days, range 13-1,394), 54 patients died, 151 received transplants (110 in high-urgency status, 41 electively), and 45 became delisted (15 deteriorated, 30 improved). Two robust findings emerged: Frequent intake of salty foods, which correlated positively with saturated fat and fluid intake, was associated with transplantation in high-urgency status (HR 2.90, 95% confidence interval [CI] 1.55-5.42); and frequent intake of foods rich in PUFA+MUFA reduced the risk for death/deterioration (HR 0.49, 95% CI 0.26-0.92). CONCLUSIONS: These results support the importance of dietary habits for the prognosis of patients listed for heart transplantation, independently from heart failure severity.

Triazole-based inhibitors of geranylgeranyltransferase II.

A small set of triazole bisphosphonates has been prepared and tested for the ability to inhibit geranylgeranyltransferase II (GGTase II). The compounds were prepared through use of click chemistry to assemble a central triazole that links a polar head group to a hydrophobic tail. The resulting compounds were tested for their ability to inhibit GGTase II in an in vitro enzyme assay and also were tested for cytotoxic activity in an MTT assay with the human myeloma RPMI-8226 cell line. The most potent enzyme inhibitor was the triazole with a geranylgeranyl tail, which suggests that inhibitors that can access the enzyme region that holds the isoprenoid tail will display greater activity.

The making of a pan-European organ transplant registry.

A European patient registry to track the outcomes of organ transplant recipients does not exist. As knowledge gleaned from large registries has already led to the creation of standards of care that gained widespread support from patients and healthcare providers, the European Union initiated a project that would enable the creation of a European Registry linking currently existing national databases. This report contains a description of all functional, technical, and legal prerequisites, which upon fulfillment should allow for the seamless sharing of national longitudinal data across temporal, geographical, and subspecialty boundaries. To create a platform that can effortlessly link multiple databases and maintain the integrity of the existing national databases crucial elements were described during the project. These elements are: (i) use of a common dictionary, (ii) use of a common database and refined data uploading technology, (iii) use of standard methodology to allow uniform protocol driven and meaningful long-term follow-up analyses, (iv) use of a quality assurance mechanism to guarantee completeness and accuracy of the data collected, and (v) establishment of a solid legal framework that allows for safe data exchange.

Outcomes in patients with cardiac amyloidosis undergoing heart transplantation: the eurotransplant experience.

BACKGROUND: When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival. METHODS: Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable. RESULTS: Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model. CONCLUSIONS: HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.

Machine perfusion or cold storage in deceased-donor kidney transplantation.

BACKGROUND: Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. METHODS: In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. RESULTS: Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. CONCLUSIONS: Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

Time trend in access to the waiting list and renal transplantation: a comparison of four European countries.

BACKGROUND: To examine the time trend and international differences in access to the waiting list and renal transplantation of patients with end-stage kidney disease. METHODS: We included all patients (n = 30 961) from Austria, Norway, the Netherlands and Scotland who started renal replacement therapy (RRT) between 1995 and 2003 with their kidney transplant waiting list data (until 31 December 2005) and follow-up data on RRT and mortality (until 31 December 2007). The outcome measure was access to the waiting list within 2 years and to a first renal transplant within 4 years from the start of RRT, expressed as incidence per million age-related population (p.m.a.r.p.) per year. To estimate trends over time, mean percentage annual change (MPAC) and 95% confidence interval (CI) were calculated. RESULTS: In each country, the number of patients starting RRT > 65 years increased significantly over time, whereas the number of renal transplants did not increase to the same extent. Only in Norway were almost all patients on the waiting list transplanted within 4 years of RRT start if they were < 65 years. In patients who started RRT > 65 years, the access to renal transplantation was high in Norway (49 p.m.a.r.p.) and low in Austria ( < 26 p.m.a.r.p.), the Netherlands and Scotland (both < 10 p.m.a.r.p.) but increased significantly in Austria (MPAC = 9.8%; 95% CI = 3.9-16.9) and the Netherlands (MPAC = 9.0%; 95% CI = 3.2-15.0). CONCLUSION: Only in Norway, virtually all patients on the waiting list < 65 years received a transplant within 4 years after the start of RRT and, remarkably, also most of those > 65 years of age.