Waitlist Outcomes in Candidates With Rare Causes of Heart Failure After Implementation of the 2018 French Heart Allocation Scheme.

BACKGROUND: In 2018, an algorithm-based allocation system for heart transplantation (HT) was implemented in France. Its effect on access to HT of patients with rare causes of heart failure (HF) has not been assessed. METHODS: In this national study, including adults listed for HT between 2018 and 2020, we analyzed waitlist and posttransplant outcomes of candidates with rare causes of HF (restrictive cardiomyopathy [RCM], hypertrophic cardiomyopathy, and congenital heart disease). The primary end point was death on the waitlist or delisting for clinical deterioration. Secondary end points included access to HT and posttransplant mortality. The cumulative incidence of waitlist mortality estimated with competing risk analysis and incidence of transplantation were compared between diagnosis groups. The association of HF cause with outcomes was determined by Fine-Gray or Cox models. RESULTS: Overall, 1604 candidates were listed for HT. At 1 year postlisting, 175 patients met the primary end point and 1040 underwent HT. Candidates listed for rare causes of HF significantly differed in baseline characteristics and had more frequent score exceptions compared with other cardiomyopathies (31.3%, 32.0%, 36.4%, and 16.7% for patients with hypertrophic cardiomyopathy, RCM, congenital heart disease, and other cardiomyopathies). The cumulative incidence of death on the waitlist and probability of HT were similar between diagnosis groups (P=0.17 and 0.40, respectively). The adjusted risk of death or delisting for clinical deterioration did not significantly differ between candidates with rare and common causes of HF (subdistribution hazard ratio (HR): hypertrophic cardiomyopathy, 0.51 [95% CI, 0.19-1.38]; P=0.18; RCM, 1.04 [95% CI, 0.42-2.58]; P=0.94; congenital heart disease, 1.82 [95% CI, 0.78-4.26]; P=0.17). Similarly, the access to HT did not significantly differ between causes of HF (hypertrophic cardiomyopathy: HR, 1.18 [95% CI, 0.92-1.51]; P=0.19; RCM: HR, 1.19 [95% CI, 0.90-1.58]; P=0.23; congenital heart disease: HR, 0.76 [95% CI, 0.53-1.09]; P=0.14). RCM was an independent risk factor for 1-year posttransplant mortality (HR, 2.12 [95% CI, 1.06-4.24]; P=0.03). CONCLUSIONS: Our study shows equitable waitlist outcomes among HT candidates whatever the indication for transplantation with the new French allocation scheme.

France's New Lung Transplant Allocation System: Combining Equity With Proximity by Optimizing Geographic Boundaries Through the Supply/Demand Ratio.

A new lung allocation system was introduced in France in September 2020. It aimed to reduce geographic disparities in lung allocation while maintaining proximity. In the previous two-tiered priority-based system, grafts not allocated through national high-urgency status were offered to transplant centres according to geographic criteria. Between 2013 and 2018, significant geographic disparities in transplant allocation were observed across transplant centres with a mean number of grafts offered per candidate ranging from 1.4 to 5.2. The new system redistricted the local allocation units according to supply/demand ratio, removed regional sharing and increased national sharing. The supply/demand ratio was defined as the ratio of lungs recovered within the local allocation unit to transplants performed in the centre. A driving time between the procurement and transplant centres of less than 2 h was retained for proximity. Using a brute-force algorithm, we designed new local allocation units that gave a supply/demand ratio of 0.5 for all the transplant centres. Under the new system, standard-deviation of graft offers per candidate decreased from 0.9 to 0.5 (p = 0.08) whereas the mean distance from procurement to transplant centre did not change. These preliminary results show that a supply/demand ratio-based allocation system can achieve equity while maintaining proximity.

Impact of ex vivo lung perfusion on brain-dead donor lung utilization: The French experience.

Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50 years, smoking history, PaO2 /FiO2 ratio ≤300 mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO2 /FiO2 ratio ≤300 mmHg, and abnormal chest imaging.

Access of non-residents to transplantation of deceased donor organs: practices and strategies in the European setting.

The access of non-resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non-residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non-residents. Two countries never allow non-residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non-resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life-threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non-residents to DDWL should be clearly defined at national level.

Effect of Lung-Protective Ventilation in Organ Donors on Lung Procurement and Recipient Survival.

Rationale: Previous studies have shown that a lung-protective strategy, which aims at minimizing ventilator-induced lung injury (with low Vt/high positive end-expiratory pressure as the main pillars), in selected potential organ donors after brain death increased lung eligibility and procurement.Objectives: This prospective nationwide cohort study aimed to evaluate the impact of lung-protective ventilation (PV) in nonselected donors on lung procurement and recipient survival after lung transplantation.Methods: We included all reported donors aged 18-70 years after brain death without a lung recovery contraindication and with at least one organ recovered between January 2016 and December 2017. PV was defined as Vt ≤8 ml/kg predicted body weight and positive end-expiratory pressure ≥8 cm H2O. The association between PV at the time of lung proposal (T1) and lung procurement was determined by multivariable logistic regression stratified by propensity score quintile to account for PV and non-PV group differences in baseline characteristics. We studied 1-year survival of recipients from donors with or without PV at T1.Measurements and Main Results: Of 1,626 included lung donors, 1,109 (68%) had at least one lung proposed; 678 (61%) of these had at least one lung recovered. At T1, only 25.6% of donors with at least one lung proposed for lung transplantation were ventilated with a protective strategy. For donors with a lung proposal, the probability of lung procurement was increased with PV at T1 (odds ratio, 1.43; 95% confidence interval [CI], 1.03-1.98; P = 0.03). One-year survival did not differ between recipients of lungs from donors with and without PV (82.7%, 95% CI 76.0-87.8% vs. 82.3%, 95% CI 78.5-85.4%; P = 0.94).Conclusions: The use of lung PV in nonselected donors may increase lung procurement. One-year survival did not differ between recipients of lungs from donors with PV or from those without PV.

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.

Continuous Monitoring of Transplant Center Performance: Different Options for Different Goals.

BACKGROUND: In France, the need for continuous monitoring of transplant center performance has recently become apparent. Cumulative sum (CUSUM) monitoring of transplantation is already been used to monitor transplant outcomes in the United Kingdom and in the United States. Because CUSUM monitoring can be applied by different methods, the objective was to assess and compare the performance of different CUSUM methods for detecting higher than expected (ie, excessive) graft failure rates. METHODS: Data come from the French transplant registry. Lung and kidney transplants in 2011-2013 constituted the control cohort, and those in 2014-2016 the observed cohort. The performance of CUSUM monitoring, according to center type and predefined control limits, was measured by simulation. The outcome monitored was 3-month graft failure. RESULTS: In a low-volume center with a low failure rate, 3 different types of control limits produced successful detection rates of excessive graft failures of 15%, 62%, and 73% and false alarm rates of 5%, 40%, and 52%, with 3, 1, and 1 excess failures necessary before a signal occurred. In a high-volume center with a high failure rate, successful detection rates were 83%, 93%, and 100% and false alarm rates were 5%, 16%, and 69%, with 6, 13, and 17 excess failures necessary before a signal occurred. CONCLUSIONS: CUSUM performances vary greatly depending on the type of control limit used. A new control limit set to maximize specificity and sensitivity of detection is an appropriate alternative to those commonly used. Continued attention is necessary for centers with characteristics making it difficult to obtain adequate sensitivity or sufficiently prompt response.

Performing diagnostic coronary angiography to evaluate high-risk cardiac donors: A French nationwide cohort study.

BACKGROUND: Allograft shortage might be overcome by the use of hearts from expanded-criteria donors (ECD) but their estimated high-risk of coronary artery disease (CAD) results in a limited utilization of these hearts for transplantation. We aimed to determine if performing coronary angiography (CA) in ECD enhances cardiac procurement and to develop a predictive model estimating their probability of absence of CAD. METHODS: We retrospectively used the French National Transplant Registry CRISTAL and considered all donors aged 45 to 70 with ≥ 1 organ harvested between March 2012 and June 2014 to derive a high-risk donor population. Of 515 donors with ≥ 1 CAD risk factor and no obvious contraindication for cardiac procurement, 230 underwent CA. Coefficients estimated by multivariate logistic regression models were used to evaluate the impact of CA on procurement and build the predictive model. RESULTS: Among CA donors, 133 had CAD, 53 (23%) with at least one stenosis ≥ 50%. Predictors of cardiac graft offer were female gender, age below 60, no cardiac arrest, no intravenous adrenaline/dobutamine requirement and no treated hypercholesterolemia. CA increased the probability of procurement by 9% (p = 0.028). Female gender, non-vascular cause of death, absence of diabetes and BMI ≥ 25 kg/m2 (p < 0.05) were associated with a normal CA and used for the prediction model. The area under the ROC curve of the model was 0.70. Specificity for the highest quartile was 82%. CONCLUSION: Performing CA in ECD enhances cardiac procurement. When CA is not feasible, we defined a clinical score allowing accurate estimation of normal CA probability.

Optimization of heart allocation: The transplant risk score.

The new French heart allocation system is designed to minimize waitlist mortality and extend the donor pool without a detrimental effect on posttransplant survival. This study was designed to construct a 1-year posttransplant graft-loss risk score incorporating recipient and donor characteristics. The study included all adult first single-organ recipients transplanted between 2010 and 2014 (N = 1776). This population was randomly divided in a 2:1 ratio into derivation and validation cohorts. The association of variables with 1-year graft loss was determined with a mixed Cox model with center as random effect. The predictors were used to generate a transplant-risk score (TRS). Donor-recipient matching was assessed using 2 separate recipient- and donor-risk scores. Factors associated with 1-year graft loss were recipient age >50 years, valvular cardiomyopathy and congenital heart disease, previous cardiac surgery, diabetes, mechanical ventilation, glomerular filtration rate and bilirubin, donor age >55 years, and donor sex: female. The C-index of the final model was 0.70. Correlation between observed and predicted graft loss rate was excellent for the overall cohort (r = 0.90). Hearts from high-risk donors transplanted to low-risk recipients had similar survival as those from low-risk donors. The TRS provides an accurate prediction of 1-year graft-loss risk and allows optimal donor-recipient matching.

Impact of donor coronary angiography on kidney transplantation outcomes.

Coronary angiography (CA) is the gold standard evaluation of coronary artery disease in potential multi-organ donors. This use of iodinated contrast media could lead to contrast-induced acute kidney injury and consequently to delayed graft function (DGF). All patients in France who received a kidney from a 45-70-year-old donor without medical contraindication for cardiac donation and with at least one cardiovascular risk factor were included. Recipients of preemptive kidney transplant or multi-organ transplant, or who died within the first 8 days post-transplantation were excluded. Data were obtained from CRISTAL database. From March 2012 to June 2014, 892 kidneys from 483 donors were transplanted. DGF was reported in 38.9% of the 375 kidney recipients grafted with a kidney from the 217 donors who had CA and in 45.5% of the 440 kidney recipients who received a kidney from the 257 donors without CA. Multivariate analysis showed that CA or repeated injection of iodinated contrast media did not influence the risk of DGF. CA did not increase the risk of primary non-function, the duration of DGF or post-transplantation hospital stay and did not affect the graft function at 1 year. Evaluation of potential multi-organ donors with CA does not affect kidney graft outcomes.

Hospitalisation and life support in the year before and during heart transplantation: a French national study.

Objective: The objective of this study was to define the characteristics of hospital care use during the year prior to heart transplantation. Methods: A retrospective cohort of heart transplant recipients registered on the national hospital discharge database between 2010 and 2015 was analysed. Results: In this cohort of 2379 heart transplant recipients (mean age: 48 years, 74% men), 91% had been admitted at least once, for at least 1 day, to a short-stay hospital during the year before transplantation (mean: 4.3 days), and 84% had at least one cardiovascular diagnosis (heart failure and cardiogenic shock: 60%). At least one intensive care stay was reported for 61% of patients, a rehabilitation stay was reported for 30%, mechanical circulatory support was reported for 12%, and ventilatory support was reported for 15%. The median interval between admission and transplantation was 5 days (interquartile QI-Q3, 0-16). The hospital mortality was higher for patients not hospitalised before transplantation (18% vs 15%). Their transplantation hospitalisation diagnosis, compared with patients hospitalised before transplantation, was more frequently cardiomyopathy (31% vs 27%) or heart failure (28% vs 18%), and less frequently myocardial infarction (1% vs 12%). Conclusion: This study demonstrates a high hospitalisation rate before heart transplantation and identifies three groups of patients: 1-patients with a high hospitalisation rate and terminal heart failure requiring circulatory support who experienced at least one intensive care unit stay; 2-patients with a history of hospitalisation, mainly for heart disease, without circulatory support requirement; and 3-patients with no pretransplantation overnight stay. These findings provide useful information to evaluate the medical benefits and needs for transplantation, and identify areas for improvement in heart transplantation listing criteria.

Between-center disparities in access to heart transplantation in France: contribution of candidate and center factors - A comprehensive cohort study.

Transplantation represents the last option for patients with advanced heart failure. We assessed between-center disparities in access to heart transplantation in France 1 year after registration and evaluated the contribution of factors to these disparities. Adults (n = 2347) registered on the French national waiting list between January 1, 2010, and December 31, 2014, in the 23 transplant centers were included. Associations between candidate and transplant center characteristics and access to transplantation were assessed by proportional hazards frailty models. Candidate blood groups O and A, sensitization, and body mass index ≥30 kg/m2 were independently associated with lower access to transplantation, while female gender, severity of heart failure, and high serum bilirubin levels were independently associated with greater access to transplantation. Center factors significantly associated with access to transplantation were heart donation rate in the donation service area, proportion of high-urgency candidates among listed patients, and donor heart offer decline rate. Between-center variability in access to transplantation increased by 5% after adjustment for candidate factors and decreased by 57% after adjustment for center factors. After adjustment for candidate and center factors, five centers were still outside of normal variability. These findings will be taken into account in the future French heart allocation system.

Access to Heart Transplantation: A Proper Analysis of the Competing Risks of Death and Transplantation Is Required to Optimize Graft Allocation.

BACKGROUND: Heart allocation systems are usually urgency-based, offering grafts to candidates at high risk of waitlist mortality. In the context of a revision of the heart allocation rules, we determined observed predictors of 1-year waitlist mortality in France, considering the competing risk of transplantation, to determine which candidate subgroups are favored or disadvantaged by the current allocation system. METHODS: Patients registered on the French heart waitlist between 2010 and 2013 were included. Cox cause-specific hazards and Fine and Gray subdistribution hazards were used to determine candidate characteristics associated with waitlist mortality and access to transplantation. RESULTS: Of the 2053 candidates, 7 variables were associated with 1-year waitlist mortality by the Fine and Gray method including 4 candidate characteristics related to heart failure severity (hospitalization at listing, serum natriuretic peptide level, systolic pulmonary artery pressure, and glomerular filtration rate) and 3 characteristics not associated with heart failure severity but with lower access to transplantation (blood type, age, and body mass index). Observed waitlist mortality for candidates on mechanical circulatory support was like that of others. CONCLUSIONS: The heart allocation system strongly modifies the risk of pretransplant mortality related to heart failure severity. An in-depth competing risk analysis is therefore a more appropriate method to evaluate graft allocation systems. This knowledge should help to prioritize candidates in the context of a limited donor pool.

Prediction of Waitlist Mortality in Adult Heart Transplant Candidates: The Candidate Risk Score.

BACKGROUND: The cardiac allocation system in France is currently based on urgency and geography. Medical urgency is defined by therapies without considering objective patient mortality risk factors. This study aimed to develop a waitlist mortality risk score from commonly available candidate variables. METHODS: The study included all patients, aged 16 years or older, registered on the national registry CRISTAL for first single-organ heart transplantation between January 2010 and December 2014. This population was randomly divided in a 2:1 ratio into derivation and validation cohorts. The association of variables at listing with 1-year waitlist death or delisting for worsening medical condition was assessed within the derivation cohort. The predictors were used to generate a candidate risk score (CRS). Validation of the CRS was performed in the validation cohort. Concordance probability estimation (CPE) was used to evaluate the discriminative capacity of the models. RESULTS: During the study period, 2333 patients were newly listed. The derivation (n =1 555) and the validation cohorts (n = 778) were similar. Short-term mechanical circulatory support, natriuretic peptide decile, glomerular filtration rate, and total bilirubin level were included in a simplified model and incorporated into the score. The Concordance probability estimation of the CRS was 0.73 in the derivation cohort and 0.71 in the validation cohort. The correlation between observed and expected 1-year waitlist mortality in the validation cohort was 0.87. CONCLUSIONS: The candidate risk score provides an accurate objective prediction of waitlist mortality. It is currently being used to develop a modified cardiac allocation system in France.

Heart transplantation in selected patients aged 60 years and older: a two-decade retrospective and multicentre analysis.

OBJECTIVES: This study analysed survival and long-term outcomes of heart transplantation in patients aged 60 years and older. We also analysed the impact of a national graft allocation priority [Super Emergency (SE)] and compared survival with younger patients in our centres and in France. METHODS: We performed a multicentre (University Hospitals in Nantes, Rennes and Tours), 2-decade retrospective study between 1 January 1994 and 31 December 2013. Elderly recipients were placed on the same list as younger patients; the use of marginal donors remained occasional. RESULTS: A total of 212 patients aged between 60 and 68 years were included. The 1-, 5-, and 10-year survival rates were 83.2%, 77.4% and 63.8%, respectively, which were significantly worse than those of recipients aged <60 years (1-, 5-, and 10-year survival rates of 87.3%, 80.4% and 68.0%, respectively). The postoperative course was acceptable. The main cause of death was malignancy (29.8% in our cohort). Survival was similar between the first and second decades and among the SE group. Our population exhibited better survival than patients <60 years transplanted in France during the same period with 1-, 5-, and 10-year survival rates of 76.8%, 68.0% and 56.3%, respectively. Predictors of survival in the multivariate analysis included ischaemic cardiomyopathy [hazard ratio (HR) 4.1] and postoperative complications, such as dialysis (HR 9.5) and mechanical circulatory support (HR 4.2). CONCLUSIONS: We report positive postoperative course and long-term outcomes after heart transplantation in older recipients using conventional donors. Our satisfactory outcomes may be explained by the stringent selection of recipients combined with regular follow-up.

Impact of Heart Transplantation on Survival in Patients on Venoarterial Extracorporeal Membrane Oxygenation at Listing in France.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a short-term circulatory support in patients with refractory cardiogenic shock providing a bridge to long-term mechanical circulatory support or transplantation. In France, a higher priority status is granted to transplant candidates on VA-ECMO than to those on long-term mechanical circulatory support. This study aimed to evaluate the impact of transplantation as primary therapy on survival in patients on VA-ECMO at listing. METHODS: This was a retrospective analysis of data from the French national registry CRISTAL including all patients (n = 866) newly registered on the waiting list for heart transplantation between January 2010 and December 2011. We compared outcomes of 80 patients on VA-ECMO at listing to outcomes of the comparison group. In the VA-ECMO group, a Cox proportional hazard model with transplantation as a time dependent variable was used to evaluate the effect of transplantation on survival. RESULTS: Patients on VA-ECMO were more often on ventilator and dialysis and had a higher bilirubin level than other candidates. One-year overall survival rate was lower in candidates from the study group (52.2%) compared with comparison group (75.5%), (P < 0.01). One-year posttransplant survival was 70% in the VA-ECMO group and 81% in comparison group (P = 0.06). In the VA-ECMO group, transplantation was associated with a lower risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.2-0.9). CONCLUSIONS: Transplantation provides a survival benefit in listed patients on VA-ECMO even if posttransplant survival remains inferior than for patients without VA-ECMO. Transplantation may be considered to be an acceptable primary therapy in selected patients on VA-ECMO.

[Heart transplantation in France: Current status]. / La greffe cardiaque en France : bilan actuel.

The ratio of candidates per transplant is 2.1. Forty-eight percent of candidates have been transplanted within 12months of listing. Twenty-five French centers performed 397 heart transplants in 2012 (6.1 pmp). Forty-eight percent of patients receiving a transplant have an urgency status. One-year survival is 76%. The annual attrition rate is 2-3% in patients surviving the first year. Risk factors for 1-year mortality are donor specific, center specific and recipient specific. Patient-based graft allocation policy requires a reliable measure of mortality risk in candidates as well as of transplant benefit.