Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates.

Importance: The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability. Objective: To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data. Design, Setting, and Participants: A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022. Main Outcomes and Measures: A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC. Results: A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%. Conclusions and Relevance: In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.

Removing administrative boundaries using a gravity model for a national liver allocation system.

Geographic disparities emerged as an increasing issue in organ allocation policies. Because of the sequential and discrete geographical models used for allocation scores, artificial regional boundaries may impede the access of candidates with the greatest medical urgency to vital organs. This article describes a continuous geographical allocation model that provides accurate organ access by introducing a multiplicative interaction between the patient's condition and the distance to the graft by using a gravity model. Patients with the most urgent need will thus have access to organs from farther away, while those in less urgent need may only have access to organs geographically closer. Compared to the previous French liver allocation scheme, the gravity model precluded transplantations for candidates with a Model for End-Stage Liver Disease (MELD) ≤ 14 for decompensated cirrhosis from 10.3% to 0.6%. Death and delisting while on the waiting list at 1 year also decreased from 30.1% to 22.4% for MELD ≥ 35. Waiting list (cumulative hazard ratio (CHR)  0.84 after adjustment) and posttransplant survival improved significantly (hazard ratio = 0.83 after adjustment). This new liver allocation system provides more equitable access to liver transplants and an efficient and safe alternative to administrative boundaries for geographical models in organ allocation.

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.

Liver Transplantation From Controlled Donors After Circulatory Death Using Normothermic Regional Perfusion: An Initial French Experience.

A national program of controlled donation after circulatory death (cDCD) began in France in 2014 involving the use of a standardized national protocol that involves the systematic use of normothermic regional perfusion (NRP). In this article, we describe in detail the French cDCD program. Between January 1, 2015, and December 31, 2018, 225 livers were offered for donation, resulting in 123 cDCD liver transplantations (LTs). The overall 90-day graft survival rate was 93.1% (95% confidence interval [CI], 85.9%-96.6%). A total of 21 of 123 LTs (17%) did not adhere strictly to the national protocol. The 1-year graft survival was significantly lower in the group deviating from the national protocol compared with those patients following the national protocol: 68.4% (95% CI, 42.8%-84.4%) versus 94.8% (95% CI, 86.5%-98.0%; P < 0.01). There were 14 patients who died, including 2 after primary 2 after primary non function, and 10 related to liver cancer recurrence. Only 1 case of ischemic cholangiopathy was observed at month 18 in this series, and the patient underwent a successful retransplant. During the first 4 years, excellent LT results were observed where the national protocol was followed. Systematic use of NRP limits liver damage induced by warm ischemia and provides excellent cDCD organs for transplant.

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 the new MELD-based allocation system on waiting list and post-transplant survival - a cohort analysis using the French national CRISTAL database.

Concerns related to equity and efficacy of our previous center-based allocation system have led us to introduce a patient-based allocation system called the "Liver Score" that incorporates the MELD score. The main objective of this study was to compare waitlist and post-transplant survivals before and after implementation of the "Liver Score" using the French transplant registry (period before: 2004-2006 and period after: 2007-2012). Patients transplanted during the second period were sicker and had a higher MELD. One-year waitlist survival (74% versus 76%; p=0.8) and one-year post-transplant survival (86.3% vs 85.7%; p=0.5) were similar between the 2 periods. Cirrhotic recipients with MELD>35 had lower one-year post-transplant survival compared to those with MELD<35 (74.8% vs 86.3%; p<0.01), mainly explained by their higher intubation and renal failure rates. The MELD showed a poor discriminative capacity. In cirrhotic recipients with MELD>35, patients presenting 2 or 3 risk factors (dialysis, intubation or infection) had a lower 1-year survival compared to those with none of these risk factors (61.2% vs 92%; p<0.01). The implementation of the MELD-based allocation system has led to transplant sicker patients with no impact on waitlist and post-transplant survivals. Nevertheless, selection of patients with MELD>35 should be completed to allow safe transplantation. This article is protected by copyright. All rights reserved.

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.

Cesarean section for HIV-infected women in the combination antiretroviral therapies era, 2000-2010.

OBJECTIVE: Elective cesarean section (CS) is a proven method to prevent mother-to-child transmission (MTCT), but is no longer recommended for women with antiretroviral therapy resulting in a low viral load (VL): <400 copies/mL in French and <1000 copies/mL in US guidelines. We sought to describe mode of delivery practices in human immunodeficiency virus (HIV)-infected women and their association with MTCT and postpartum complications. STUDY DESIGN: All deliveries from HIV-1-infected women in the French Perinatal Cohort (Agence Nationale de Recherches sur le Sida/Enquête Périnatale Française) 2000 through 2010 (N = 8977) were analyzed, with additional details for 2005 through 2010 (n = 4717). RESULTS: Vaginal deliveries increased from 25% in 2000 to 53% in 2010. Over 2005 through 2010, 4300 women had VL before delivery <400 copies/mL; among them only 49.3% delivered vaginally, 22.0% had nonelective CS, and 28.7% had elective CS. Elective CS were performed for scarred uterus in 45.4%, other obstetrical indications in 37.1%, and solely because of HIV in 15.7%. Of the 417 women with VL ≥400 copies/mL, 48.9% had elective CS as recommended, 25.9% had nonelective CS, and 25.2% had vaginal delivery. The MTCT rate did not differ according to the mode of delivery in term deliveries (≥37 gestational weeks) in 2000 through 2010: 0.3% after both vaginal delivery and elective CS with VL <50 copies/mL, 4.0% vs 5.3%, respectively, with VL ≥10,000 copies/mL. In case of preterm delivery, MTCT rates tended to be higher with vaginal delivery. Postpartum complications were more frequent following CS than vaginal deliveries (6.5% vs 2.9, P < .01). CONCLUSION: Our findings suggest that HIV-infected women on antiretroviral therapy with low VL can safely opt for vaginal delivery in the absence of obstetrical risk factors.

Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France.

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.

Impact of direct antiviral agents for hepatitis C virus -induced liver diseases on registration, waiting list and liver transplant activity in France.

Direct-acting antivirals (DAA) has dramatically improved the prognosis of liver transplantation (LT) candidates for HCV end-stage liver disease (ESLD). We aimed to evaluate the impact of DAA on waiting list (WL) registration and LT activity in France. We evaluated all patients registered to the French WL for HCV ESLD between 2000 and 2018. Timespan was divided into two periods according to DAA availability: 2010-2013 versus 2014-2018. Changes in the indications of LT, outcome on WL were evaluated. Then, we evaluated the activity of LT and outcome for HCV recipients in France. Among 3,173 HCV candidates, registration on WL decreased by 33% between 2013 and 2018. The 1-year waitlist survival increased from 76.9% (95%CI: 74.2%-79.4%) in 2010-2013 to 79.8% (95%CI: 77.2%-82.1%) in 2014-2018 (p < 0.01). Regarding LT activity, the part of HCV ESLD decreased from 26% in 2010 to 16% in 2018. The 1-year graft survival rate in HCV recipients increased from 76.9% (95%CI: 73.7%-79.7%) in 2010-2012 to 84.9% (95%CI: 82.9%-86.7%) in 2013-2018 (p < 0.01). The availability of DAA to treat HCV infection is associated with a significant decrease of registration for LT, death and drop out for worsening condition on the LT. In addition, it has decreased the number of HCV+ LT and improved the 1-year graft survival in France.

Performance of HIV-1 DNA or HIV-1 RNA tests for early diagnosis of perinatal HIV-1 infection during anti-retroviral prophylaxis.

OBJECTIVE: To compare performance of testing for human immunodeficiency virus (HIV)-1 DNA and HIV-1 RNA for diagnosis of HIV-1 infection in infants receiving preventive antiretroviral therapy. STUDY DESIGN: This substudy of the French multicenter prospective cohort of neonates born to HIV-infected mothers, included 1567 infants tested for HIV with polymerase chain reaction (PCR) in a single laboratory, receiving post-natal prophylaxis, not breastfed, and having simultaneous HIV-1 DNA and RNA results before 45 days. The performance of PCR was assessed in reference to the 6-month HIV-1 RNA result. RESULTS: Specificity of both HIV-1 RNA and HIV-1 DNA PCR was 100% at all ages (except 99.8% for DNA at birth); sensitivity was 58% (RNA) and 55% (DNA) at birth, and 89% at 1 month, 100% at 3 months for both, and 100% at 6 months (DNA). Concordance between HIV-1 DNA and RNA results was 0.78 and 0.81 (Kappa) at birth and 1 month and 100% at 3 and 6 months. Type of maternal and neonatal prophylaxis had no effect on sensitivity, but influenced viral load. CONCLUSION: The performances of testing for HIV-1 DNA and RNA were similar with 100% sensitivity at 3 months. At 1 month during prophylaxis, 11% of infected children had negative PCR results.

Liver transplantation for critically ill cirrhotic patients: Results from the French transplant registry.

This study describes the population of cirrhotic patients who were transplanted from the ICU in France, identifying pre-transplant risk factors of post-transplant mortality and describing geographic variations in ICU transplant activity. Cirrhotic patients transplanted between 2008 and 2018 were included through the national transplant registry. The demographic, clinical and biological characteristics of the patients transplanted from the ICU were compared to cirrhotic patients who were transplanted from home or from the hospital. Risk factors of post-transplant one-year mortality were identified in uni- and multivariable analysis within the population transplanted from the ICU. Funnel plots were used to illustrate center-specific differences in ICU transplant activity. 1,047 cirrhotic patients were transplanted from the ICU during the study period. While the national rate of transplants performed from the ICU was 14.3% the absolute number and the rate of cirrhotic patients transplanted from the ICU varied significantly from one center to another, ranging from 6.6% to 22.8% (p < 0.05). Three recipient-associated independent risk factors one-year post-LT mortality were identified in the population transplanted from the ICU: age > 50 years (HR 1.65, 95%CI 1.16-2.36), p = 0.005), diabetes (HR 1.46, 95%CI 1.07-1.98, p = 0.02) and intubation (HR2.12, 95%CI 1.62-2.78), p < 0.001). Donor age was also independently associated with mortality (HR 1.01, 95%CI 1.01-1.02, p < 0.001). Funnel plots showed significant differences in the proportion of patients transplanted from the ICU and the distribution of risk factors across French transplant centers, especially the inclination to transplant intubated patients. This study underlines the increased post-transplant mortality among cirrhotic patients transplanted from the ICU. It identifies four clinically pertinent independent risk factors associated with post-transplant mortality in this specific sub-group of transplant candidates. Finally, it illustrates how diverse the landscape of liver transplantation for critically ill cirrhotic patients is across a single country, despite a unified allocation algorithm.

Favorable Outcomes of Liver Transplantation from Controlled Circulatory Death Donors Using Normothermic Regional Perfusion Compared to Brain Death Donors.

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.

Amniocentesis and mother-to-child human immunodeficiency virus transmission in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales French Perinatal Cohort.

OBJECTIVE: The objective of the study was to investigate whether performing an amniocentesis increased mother-to-child transmission of human immunodeficiency virus (HIV)-1 (MTCT). STUDY DESIGN: We studied HIV -1 infected mothers and their children enrolled in the multicenter French Perinatal HIV Cohort from 1985 to 2006. RESULTS: One hundred sixty-six amniocenteses were performed among 9302 singleton pregnancies, the proportion increasing from 1.0% before 2001 to 4.7% in 2005-2006. Use of highly active antiretroviral therapy (HAART) was more frequent in the amniocentesis group (58.4% vs 33.2%). MTCT tended to be higher in the amniocentesis group, among mothers who received no antiretroviral agents (25.0%; 3/12 vs 16.2%; 343/2113; P = .41) as well as among mothers receiving zidovudine monotherapy or a double-nucleoside reverse transcriptase inhibitor combination (6.1%; 3/49 vs 3.3%; 117/3556; P = .22), but the difference was not significant. Among 81 mothers receiving HAART, there was no case of MTCT. CONCLUSION: Our results suggest that amniocentesis is not a major risk factor for mother-to-child transmission in mothers treated with effective antiretroviral therapy.

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.

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.

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.