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1.
Thorax ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768985

ABSTRACT

INTRODUCTION: Lung graft allocation can be based on a score (Lung Allocation Score) as in the USA or sequential proposals combined with a discrete priority model as in France. We aimed to analyse the impact of allocation policy on the outcome of urgent lung transplantation (LT). METHODS: US United Network for Organ Sharing (UNOS) and French Cristal databases were retrospectively reviewed to analyse LT performed between 2007 and 2017. We analysed the mortality risk of urgent LT by fitting Cox models and adjusted Restricted Mean Survival Time. We then compared the outcome after urgent LT in the UNOS and Cristal groups using a propensity score matching. RESULTS: After exclusion of patients with chronic obstructive pulmonary disease/emphysema and redo LT, 3775 and 12 561 patients underwent urgent LT and non-urgent LT in the USA while 600 and 2071 patients underwent urgent LT and non-urgent LT in France. In univariate analysis, urgent LT was associated with an HR for death of 1.24 (95% CI 1.05 to 1.48) in the Cristal group and 1.12 (95% CI 1.05 to 1.19) in the UNOS group. In multivariate analysis, the effect of urgent LT was attenuated and no longer statistically significant in the Cristal database (HR 1.1 (95% CI 0.91 to 1.33)) while it remained constant and statistically significant in the UNOS database (HR 1.12 (95% CI 1.05 to 1.2)). Survival comparison of urgent LT patients between the two countries was significantly different in favour of the UNOS group (1-year survival rates 84.1% (80.9%-87.3%) vs 75.4% (71.8%-79.1%) and 3-year survival rates 66.3% (61.9%-71.1%) vs 62.7% (58.5%-67.1%), respectively). CONCLUSION: Urgent LT is associated with adverse outcome in the USA and in France with a better prognosis in the US score-based system taking post-transplant survival into account. This difference between two healthcare systems is multifactorial.

2.
JAMA ; 331(6): 500-509, 2024 02 13.
Article in English | MEDLINE | ID: mdl-38349372

ABSTRACT

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.


Subject(s)
Heart Failure , Heart Transplantation , Tissue and Organ Procurement , Adult , Female , Humans , Male , Middle Aged , Bilirubin , Clinical Laboratory Services , Heart , Risk Factors , Risk Assessment , Heart Failure/mortality , Heart Failure/surgery , United States , Health Care Rationing/methods , Predictive Value of Tests , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/organization & administration
3.
Circ Heart Fail ; 17(2): e010837, 2024 02.
Article in English | MEDLINE | ID: mdl-38299331

ABSTRACT

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.


Subject(s)
Cardiomyopathies , Cardiomyopathy, Hypertrophic , Cardiomyopathy, Restrictive , Clinical Deterioration , Heart Defects, Congenital , Heart Failure , Heart Transplantation , Adult , Humans , Heart Failure/diagnosis , Heart Failure/surgery , Heart Failure/complications , Cardiomyopathies/complications , Heart Transplantation/adverse effects , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Restrictive/complications , Waiting Lists , Retrospective Studies
4.
J Infect Dis ; 229(4): 1041-1049, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-37956413

ABSTRACT

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics. METHODS: From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host. RESULTS: Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts. CONCLUSIONS: This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Case-Control Studies , Retrospective Studies , SARS-CoV-2/genetics , Immunocompromised Host , Mutation
5.
PLoS One ; 18(10): e0291860, 2023.
Article in English | MEDLINE | ID: mdl-37797039

ABSTRACT

OBJECTIVES: This study described the demographic characteristics, clinical presentation, treatment, and outcomes of solid organ transplant recipients who were admitted to our center for infection. It also determined factors associated with a poor outcome, and compares early and late period infections. METHODS: In this retrospective observational study, conducted at a tertiary care center in France between October 2017 and March 2019, infectious outcomes of patients with solid organ transplant where studied. RESULTS: A total of 104 patients were included with 158 hospitalizations for infection. Among these 104 patients, 71 (68%) were men. The median age was 59 years old. The most common symptoms on admission were fever (66%) and chills (31%). Lower respiratory tract infections were the most common diagnosis (71/158 hospitalizations). Urinary tract infections were frequently seen in kidney transplant recipients (25/60 hospitalizations). One or more infectious agents were isolated for 113 hospitalizations (72%): 70 bacteria, 36 viruses and 10 fungi, with predominance of gram-negative bacilli (53 cases) of which 13 were multidrug-resistant. The most frequently used antibiotics were third generation cephalosporins (40 cases), followed by piperacillin-tazobactam (26 cases). We note that 25 infections (16%) occurred during the first 6 months (early post-transplant period). Patients admitted during the early post-transplant period were more often on immunosuppressive treatment with prednisone (25/25 VS 106/133) (p = 0.01), mycophenolic acid (22/25 VS 86/133) (p = 0.03), presented for an urinary tract infection (10/25 VS 25/133) (p = 0.04) or a bacterial infection (17/25 VS 53/133) (p = 0.01). Patients with later infection had more comorbidities (57/83 VS 9/21) (p = 0.03), cancer (19/83 VS 0/21) (p = 0.04) or were on treatment with everolimus (46/133 VS 0/25) (p = 0.001). During 31 hospitalizations (20%), patients presented with a serious infection requiring intensive care (n = 26; 16%) or leading to death (n = 7; 4%). Bacteremia, pulmonary and cardiac complications were the main risk factors associated with poor outcome. CONCLUSION: Infections pose a significant challenge in the care of solid organ transplant patients, particularly those with comorbidities and intensive immunosuppression. This underscores the crucial importance of continuous surveillance and epidemiologic monitoring within this patient population.


Subject(s)
Bacterial Infections , Organ Transplantation , Urinary Tract Infections , Male , Humans , Adult , Middle Aged , Female , Paris , Retrospective Studies , Organ Transplantation/adverse effects , Bacterial Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/drug therapy
6.
Front Endocrinol (Lausanne) ; 14: 1252966, 2023.
Article in English | MEDLINE | ID: mdl-37766687

ABSTRACT

Introduction: Significant bone loss occurs after heart transplantation, predominantly in the first year, with increased risk of incident fractures. The goal of this study was to evaluate the prevalence of fragility fractures in a population of heart transplantation patients and to identify the independent risk factors for fractures. Methods: This was a prospective monocentric study that included patients with heart transplantation occurring < 10 years who were undergoing heart transplantation monitoring. All patients underwent bone mineral density evaluation by dual-energy X-ray absorptiometry and radiographies to establish the presence of vertebral fractures. Results: We included 79 patients (61 men); the mean age was 56.8 ± 10.8 years. The mean time between transplantation and inclusion was 32.3 ± 35.0 months. Incident fractures were diagnosed in 21 (27%) patients after heart transplantation. Vertebral fractures were the most frequent (30 vertebral fractures for 15 patients). Osteoporosis was confirmed in 22 (28%) patients. Mean bone mineral density at the femoral neck and total hip was lower with than without fracture (femoral neck: 0.777 ± 0.125 vs 0.892 ± 0.174 g/cm2, p<0.01; total hip: 0.892 ± 0.165 vs 0.748 ± 0.07 g/cm2, p<0.001), with a significant result on multivariate analysis. The mean time from transplantation to the first fracture was 8.0 ± 7.6 months. Discussion: Our study confirmed a high vertebral fracture risk in heart transplant patients, especially during the first year after transplantation.


Subject(s)
Fractures, Bone , Heart Transplantation , Osteoporosis , Spinal Fractures , Male , Humans , Middle Aged , Aged , Prospective Studies , Osteoporosis/epidemiology , Osteoporosis/etiology , Bone Density , Spinal Fractures/epidemiology , Spinal Fractures/etiology , Heart Transplantation/adverse effects
7.
ESC Heart Fail ; 10(5): 2843-2852, 2023 10.
Article in English | MEDLINE | ID: mdl-37408178

ABSTRACT

AIMS: The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). METHODS AND RESULTS: All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). CONCLUSIONS: A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.


Subject(s)
Diuretics , Heart Transplantation , Male , Humans , Middle Aged , Female , Sodium Potassium Chloride Symporter Inhibitors , Prognosis , Furosemide
8.
J Heart Lung Transplant ; 42(5): 558-561, 2023 05.
Article in English | MEDLINE | ID: mdl-36822931

ABSTRACT

SARS-CoV-2 Omicron variant was first detected in France mid-November 2021 in wastewater treatment plants while cases started to increase at the beginning of December. The maximum incidence occurred in mid-January 2022. The Omicron wave spread rapidly throughout France in general population with lower case-fatality rate compared with previous waves. Little is known about infection with Omicron variant in heart transplant (HT) recipients. In this study, we examined incidence and mortality rate of COVID-19 in the general population and among 1,263 HT recipients during the period from June, 2021 to February, 2022, described characteristics of HT recipients infected with SARS-CoV-2 during Omicron (December 1st, 2021-February 7, 2022) and Delta (June 1st- November 30, 2021) periods, and compared hospital course of HT recipients with Omicron and Delta variant infection. Our findings contrast with the reported lower severity for Omicron variant infection compared with Delta variant infection in immunocompetent individuals.


Subject(s)
COVID-19 , Heart Transplantation , Humans , SARS-CoV-2 , France/epidemiology
9.
ESC Heart Fail ; 9(5): 3287-3297, 2022 10.
Article in English | MEDLINE | ID: mdl-35801277

ABSTRACT

AIMS: The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non-inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist. METHODS AND RESULTS: All non-inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The 'warm-dry', 'cold-dry', 'warm-wet', and 'cold-wet' profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the 'warm-dry' category as reference, a significant increase in the risk of primary outcome was observed only in the 'wet' categories, irrespectively of 'warm/cold' status: hazard ratios, 1.50; 1.06-2.13; P = 0.024 in 'warm-wet' and 1.77; 1. 25-2.49; P = 0.001 in 'cold-wet'. CONCLUSIONS: Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. 'Wet' patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.


Subject(s)
Heart Failure , Heart Transplantation , Humans , Risk Factors , Heart Failure/surgery , Prognosis , Waiting Lists
10.
Clin Transplant ; 36(8): e14708, 2022 08.
Article in English | MEDLINE | ID: mdl-35644026

ABSTRACT

BACKGROUND: Heart transplantation (HTX) is a well-established treatment for suitable patients with end-stage heart failure, intended to prolong their survival and improve their health-related quality of life (HR-QoL). No international consensus exists, however, about the preferred patient-reported outcomes (PROs) and their measures (PROMs) for heart transplant recipients. The purpose of this study, the first step in a mixed-method investigation, was to review the PROMs developed and used in this population to identify the instruments for measuring HR-QoL and adherence to immunosuppressive medications most appropriate for heart transplant patients. METHODS: This systematic search of the literature in the PubMed database focused on the assessment of PROMs for patients after HTX. We analyzed 66 studies with cross-sectional, 28 with longitudinal, and 2 with mixed-methods designs, as well as 6 literature reviews. RESULTS: These 102 articles used 115 different PROMs, which we categorized as generic HR-QoL instruments (n = 19), domain-specific instruments (n = 71), heart disease-specific instruments (n = 9), and heart transplant-specific instruments (n = 16). They cover different dimensions of HR-QoL and of immunosuppressive-drug experience, with diverse numbers of items, types of scales, and psychometric properties. CONCLUSIONS: Despite the abundance of instruments, PROMs for HTX can be improved to meet other patient expectations (i.e., by including important issues such as coping strategies, employment, social support, sexual relationships, spirituality, and beliefs), while paying attention to ease of use, reliability, validity, and the contribution of new technologies. A qualitative approach will complete our project of developing a patient-centered instrument for HTX patients.


Subject(s)
Heart Transplantation , Quality of Life , Cross-Sectional Studies , Humans , Patient Reported Outcome Measures , Patient-Centered Care , Registries , Reproducibility of Results , Surveys and Questionnaires
11.
Transpl Int ; 35: 10049, 2022.
Article in English | MEDLINE | ID: mdl-35686227

ABSTRACT

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.


Subject(s)
Lung Transplantation , Tissue and Organ Procurement , France , Humans , Tissue Donors , Waiting Lists
12.
Am J Transplant ; 22(5): 1409-1417, 2022 05.
Article in English | MEDLINE | ID: mdl-35000283

ABSTRACT

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.


Subject(s)
Lung Transplantation , Tissue Donors , Brain , Brain Death , Humans , Lung , Lung Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Retrospective Studies
15.
Eur Heart J ; 42(20): 2000-2011, 2021 05 21.
Article in English | MEDLINE | ID: mdl-33677556

ABSTRACT

AIMS: Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. METHODS AND RESULTS: We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10-11 and 7.7 × 10-4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10-8 and 1.4 × 10-3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. CONCLUSION: This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.


Subject(s)
Cardiomyopathy, Dilated , Heart Failure, Systolic , Adaptor Proteins, Signal Transducing/genetics , Animals , Apoptosis Regulatory Proteins , Cardiomyopathy, Dilated/genetics , Chromosomes , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Heart Failure, Systolic/genetics , Humans , Polymorphism, Single Nucleotide/genetics
16.
Transpl Int ; 34(4): 721-731, 2021 04.
Article in English | MEDLINE | ID: mdl-33539616

ABSTRACT

Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19-80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43-9.06, I2  = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39-10.31, I2  = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients.


Subject(s)
COVID-19/diagnosis , Heart Transplantation , Postoperative Complications/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/etiology , COVID-19/mortality , COVID-19/therapy , COVID-19 Testing , Female , Follow-Up Studies , France , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/mortality , Postoperative Complications/therapy , Prognosis , Prospective Studies , Respiration, Artificial/statistics & numerical data , Risk Factors , Severity of Illness Index , Young Adult
17.
Transplantation ; 105(1): 67-78, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32355121

ABSTRACT

Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series. The use of ICI became unavoidable for treating advanced cancers including in organ transplant patients, but their management in this setting remains highly challenging, as to date no strategy to adapt the immunosuppression and to prevent graft rejection has been defined. In this article, we report a monocentric series of 5 solid organ transplant recipients treated with ICI and provide a comprehensive review of current knowledge of ICI management in the setting of solid organ transplantation. Strategies warranted to increase knowledge through collecting more exhaustive data are also discussed.


Subject(s)
Graft Rejection/prevention & control , Immune Checkpoint Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Neoplasms/drug therapy , Organ Transplantation , Aged , Female , Graft Rejection/immunology , Graft Rejection/mortality , Graft Survival/drug effects , Humans , Immune Checkpoint Inhibitors/adverse effects , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Neoplasms/immunology , Neoplasms/mortality , Organ Transplantation/adverse effects , Organ Transplantation/mortality , Risk Assessment , Risk Factors , Treatment Outcome , Tumor Microenvironment
18.
Am J Respir Crit Care Med ; 202(2): 250-258, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32302488

ABSTRACT

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.


Subject(s)
Lung Transplantation/mortality , Lung Transplantation/methods , Respiration, Artificial/methods , Tissue and Organ Procurement/methods , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Survival Analysis
19.
Int J Cardiol ; 307: 94-100, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32122700

ABSTRACT

BACKGROUND: Cardiac sarcoidosis (CS) is a challenging diagnosis. Patients may progress to end-stage congestive heart failure and require cardiac transplantation without ever having been diagnosed. Characteristics and outcomes of patients with granulomas in the explanted hearts are unknown. METHODS: All French heart transplantation centers were contacted to participate in the study. Each center searched through local databases for the cases of non-caseating granuloma in the explanted hearts between 2000 and 2017. Data before and after transplantation were recorded from medical charts. Survival of CS and all- cause heart transplantation patients were compared. RESULTS: Fifteen patients (10 men, 5 women) received a diagnosis of CS based on pathologic data of the explanted heart and were recruited for the study. All patients were diagnosed as non-ischemic dilated or hypertrophic cardiomyopathy and presented congestive heart failure. Eight patients (53%) had ventricular rhythm disturbances, and 3 (20%) a complete heart block. Ten out of 13 patients (77%) had extracardiac radiological signs compatible with sarcoidosis on chest computed tomography (CT) scans. One patient died 3 months after transplantation from infectious complications. The 14 remaining patients were still alive at the end of the study (median follow-up of 28.8 months). One patient had a second heart transplantation 5 years later because of chronic allograft vasculopathy. One patient presented a relapse of CS confirmed by myocardial biopsies 9 years after transplantation, requiring an escalation of immunosuppressive therapy. CONCLUSION: CS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques.


Subject(s)
Cardiomyopathies , Heart Failure , Heart Transplantation , Sarcoidosis , Cardiomyopathies/complications , Cardiomyopathies/diagnosis , Cardiomyopathies/surgery , Female , Granuloma/complications , Granuloma/diagnosis , Granuloma/surgery , Heart Failure/diagnosis , Heart Failure/etiology , Heart Failure/surgery , Heart Transplantation/adverse effects , Humans , Male , Sarcoidosis/diagnosis , Sarcoidosis/epidemiology , Sarcoidosis/surgery
20.
Am J Transplant ; 20(5): 1236-1243, 2020 05.
Article in English | MEDLINE | ID: mdl-32037718

ABSTRACT

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.


Subject(s)
Heart Transplantation , Tissue and Organ Procurement , France , Humans , Resource Allocation , Tissue Donors , Waiting Lists
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