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International audience; BACKGROUND: The first wave of the Covid-19 pandemic resulted in a drastic reduction in kidney transplantation and a profound change in transplant care in France. It is critical for kidney transplant centers to understand the behaviors, concerns and wishes of transplant recipients and waiting list candidates. METHODS: French kidney patients were contacted to answer an online electronic survey at the end of the lockdown. RESULTS: At the end of the first wave of the pandemic in France (11 May 2020), 2112 kidney transplant recipients and 487 candidates answered the survey. More candidates than recipients left their home during the lockdown, mainly for health care (80.1% vs. 69.4%; P\textless0.001). More candidates than recipients reported being exposed to Covid-19 patients (2.7% vs. 1.2%; P=0.006). Many recipients and even more candidates felt inadequately informed by their transplant center during the pandemic (19.6% vs. 54%; P\textless0.001). Among candidates, 71.1% preferred to undergo transplant as soon as possible, 19.5% preferred to wait until Covid-19 had left their community, and 9.4% were not sure what to do. CONCLUSIONS: During the Covid-19 pandemic in France, the majority of candidates wished to receive a transplant as soon as possible without waiting until Covid-19 had left their community. Communication between kidney transplant centers and patients must be improved to better understand and serve patients' needs.

Purpose Data on outcomes in lung transplant recipients with SARS-CoV-2 infection remains limited. Given the potential higher COVID-19 severity in lung recipients, the Agence de la biomedecine has limited the transplant program to patients with high-urgency status during the first epidemic wave. The program has been fully restored where possible during the second epidemic wave. This study aimed to assess the impact of COVID-19 on lung recipient mortality in France. Methods All lung recipients with COVID-19 reported in the French national registry CRISTAL between February 1st and September 30th 2020 were included in the study. Patient characteristics were extracted from CRISTAL. Cumulative number of cases by month since February (Figure 1) and case fatality rate (CFR) were calculated. Mortality rates from February to September in the whole 2019 and 2020 recipient cohorts were compared. Survival curves were estimated using Kaplan-Meier method and compared using the log-rank test. Results Of the 46 patients (median age (IQR) 51 years (39-60), 54% female, median time from transplantation 3.5 years (0.8-7.1)) 88% required hospitalization including 21% in ICU. Eight patients died (CFR: 17.4%). No difference in 3-month survival was observed between 2020 and 2019 recipient cohorts (98.6% 95%CI [98.0%-99.0%] vs 98.4% [97.8%-98.8%], respectively) (Figure 2). Conclusion COVID-19 was associated with lower fatality rate in lung recipients than in other organ transplant recipients and did not result in an excess mortality. These findings suggest that continuing lung transplant activity during the COVID-19 pandemic was a reasonable option.

Purpose The COVID-19 pandemic has deeply affected organ transplant activity across the world. While the Agence de la biomedecine in agreement with the French lung transplant community has limited the transplant program to patients with high-urgency status during the first epidemic wave, the program has been fully restored where possible during the second epidemic wave. This study aimed to examine the impact of COVID-19 on new listings, waitlist outcomes and transplant activity in France. Methods All patients newly registered on the national waiting list for lung transplantation between January and September 2018-2020 were included in the study (n=878). The numbers of new listings and transplants per million population (pmp) in 2018-2019 period and in 2020 COVID era were compared. Cumulative incidence of transplantation and waitlist mortality estimated with the competing risk analysis with transplantation and death or delisting for medical condition as the competing events were compared between the study periods. Results In 2020 compared with the 2018-2019 period, the total number of patients newly registered on the waiting list declined 34%, from 4.9 to 3.2 pmp and the number of transplants performed decreased 31%, from 3.9 to 2.6 pmp. While 3-month cumulative incidence of transplantation (Figure 1) decreased from 54% [51-58] to 46% [39-53], no difference in cumulative incidence of death or delisting for medical condition (3% [2-4] versus 4% [2-8]) (Figure 2) was observed between the periods. Conclusion In 2020 COVID era, the waitlist and transplant access significantly declined in France without change in waitlist mortality.

OBJECTIVES: The objectives of this study were to: (1) explore the proportion of HTx centers that have a multidisciplinary team and (2) assess the relationship between multidisciplinarity and the level of chronic illness management (CIM). BACKGROUND: The International Society for Heart and Lung Transplantation (ISHLT) recommends a multidisciplinary approach in heart transplant (HTx) follow-up care but little is known regarding the proportion of HTx centers that meet this recommendation and the impact on patient care. HTx centers with a multidisciplinary team may offer higher levels of CIM, a care model that has the potential to improve outcomes after HTx. METHODS: We conducted a secondary analysis of the BRIGHT study, a cross-sectional study in 11 countries. Multidisciplinarity in the 36 HTx centers was assessed through HTx director reports and was defined as having a team that was composed of physician(s), nurse(s), and another healthcare professional (either a social worker, psychiatrist, psychologist, pharmacist, dietician, physical therapist, or occupational therapist). CIM was assessed with the Patient Assessment of Chronic Illness Care (PACIC). Multiple linear regression assessed the relationship between multidisciplinarity and the level of CIM. RESULTS: Twenty-nine (80.6%) of the HTx centers had a multidisciplinary team. Furthermore, multidisciplinarity was significantly associated with higher levels of CIM (β = 5.2, P = 0.042). CONCLUSION: Majority of the HTx centers follows the ISHLT recommendation for a multidisciplinary approach. Multidisciplinarity was associated with CIM and point toward a structural factor that needs to be in place for moving toward CIM. ispartof: Heart & Lung vol:46 issue:5 pages:351-356 ispartof: location:United States status: published

We read with interest the paper by Psotka et al. ([1][1]) showing that the mean 1-year rates of heart failure clinical trial publication or reporting are low (

PURPOSE: To assess and compare the prevalence of medication nonadherence (MNA) (implementation and persistence) to immunosuppressants and co-medications in heart transplant recipients. METHODS: MNA prevalence was assessed using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (self-report) and compared using logistic regression in a 4-continent sample of 1397 heart transplant recipients from 36 heart transplant centers in 11 countries. FINDINGS: MNA was significantly (α = 0.05) higher to co-medications than to immunosuppressants (taking nonadherence: 23.9% vs 17.3%; odds ratio [OR] = 1.5; 95% CI, 1.30-1.73; drug holiday: 5.7% vs 1.9%; OR = 3.17; 95% CI, 2.13-4.73; dose alteration: 3.8% vs 1.6%; OR = 2.46; 95% CI, 1.49-4.06; and discontinuation: 2.6% vs 0.5%; OR = 5.15; 95% CI, 2.36-11.20). IMPLICATIONS: The observed MNA necessitates adherence-enhancing interventions encompassing the entire post-heart transplant medication regimen. ClinicalTrials.gov identifier: NCT01608477. ispartof: CLINICAL THERAPEUTICS vol:41 issue:1 pages:130-136 ispartof: location:United States status: published

Background The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. Methods This retrospective study registered all cases of post-transplant melanoma in kidney, heart, lung and liver transplant recipients followed in our specialized post-transplant Dermatology clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 were computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age- and sex- standardized incidence ratio (SIR) was calculated using a renal transplantation registry. Results In our overall OTR cohort, between 1991 and 2000 five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9fold increase in prevalence after 2000. Remarkably, the prevalence of non-melanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow-up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Conclusion Our data suggest that, contrasting with non-melanoma skin cancer, the risk of post-transplant melanoma has considerably increased over the last decade. This article is protected by copyright. All rights reserved.

Aims Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients. Methods We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events. Results Eight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [−1.17, 12.03] P = 0.32 I2 = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min−1, P = 0.0003] and at 12 months 4.63 [−4.55, 13.82] P = 0.32 I2 = 75%. Conclusions This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.

Objectives We sought to evaluate the frequency of cardiovascular risk factors in a cohort of patients 10 years after a liver transplant, and to assess their 10-year risk of fatal cardiovascular disease using Systematic COronary Risk Evaluation (SCORE) charts. Materials and methods Between January 1990 and June 1996, one hundred eighty-nine adults underwent a first liver transplant in our center. Fifty-nine patients (31%) died before reaching their tenth year, and 115 patients were available with complete clinical data at 10 years. Results The main indications for liver transplant were alcoholic (38%) and viral cirrhosis (40%). The median age of patients was 56 (range, 29-73 y), 80% were men, 23% were obese, 16% were active smokers, 18% were diabetic, 40% had hypercholesterolemia, and 77% had hypertension. Before the tenth year after transplant, 6 deaths were because of cardiovascular diseases, which represents the third cause of late death (> 1 year after liver transplant). After liver transplant, 5% of the surviving patients underwent ischemic cardiovascular events during the first decade. At a 10-year assessment, the median estimated 10-year risk of fatal cardiovascular disease was 1% (range, 0%-9%) and 10% of the patients had a high risk (ie, SCORE ≥ 5%). Conclusions Our results suggest that the frequency of cardiovascular events is relatively low after a liver transplant, even if most of the patients had 1 or more cardiovascular risk factors. Nevertheless, clinicians should perform a similar evaluation 15 or 20 years after the liver transplant because cardiovascular risk exponentially increases with age.

Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.

Background Outcomes in recipients who have undergone combined heart and kidney transplantation have mainly been addressed in small, single-center studies. We studied long-term results of combined heart and kidney transplantation in a large multicenter cohort. Methods Between 1984 and 2007, 67 consecutive patients (61 men and 6 women) from 3 French centers underwent combined heart and kidney transplantation. At transplantation, 38 (57%) were receiving dialysis. All patients received immediate triple immunosuppression therapy (anti-calcineurin, steroids, azathioprine, or mycophenolate). Results Overall actuarial survival rates were 62.0%, 60.3%, 53.3%, and 46.5% at 1, 3, 5, and 10 years, respectively. These rates were similar to those observed in 2981 isolated heart recipients at the 3 participating centers during the same period (respectively, 71.0%, 65.2%, 60.1%, and 47.2%, p = 0.6). Survival tended to improve during the last decade (1996 to 2007) and reached 71.1%, 67.5%, and 60% at 1, 3, and 5 years. Cardiac allograft rejection requiring treatment occurred in 12 (17.9%). Coronary artery vasculopathy developed in 3 (9.3%). Kidney allograft rejection occurred in 9 (13.4%). Kidney graft survival was 95.9% at 1, 3, 5, and 10 years. Conclusions Long-term survival rates in a large cohort of combined heart and kidney recipients are similar to those of isolated heart recipients in France. The rates of acute heart and kidney rejection and angiographic coronary artery vasculopathy were low in this patient population.

Introduction Les inhibiteurs de la proteine mTOR, dotes de proprietes antitumorales, sont de plus en plus utilises chez les patients greffes ayant des cancers cutanes. La majorite des donnees concerne le sirolimus en greffe renale ; en revanche, peu de donnees existent sur l’everolimus (EV). Une etude observationnelle a montre une tendance a la reduction de la carcinogenese cutanee chez les greffes cardiaques (GC) sous EV. Le but de ce travail a ete d’evaluer de facon prospective l’effet antitumoral et la tolerance de l’EV chez des GC ayant des carcinomes cutanes. Materiel et methodes Etude randomisee, ouverte, comparative et multicentrique analysant l’effet sur la survenue de cancers cutanes a 2 ans de deux strategies immunosuppressives : diminution des anticalcineurines (ACN) vs. remplacement des ACN par l’EV ; chez des GC sous ACN ayant eu au moins un carcinome epidermoide (CE) ou au moins deux tumeurs de type carcinome basocellulaire (CBC) ou maladie de Bowen (MB) ; ou au moins 50 lesions verruco-keratosiques. Le critere d’evaluation principal etait la survenue de nouvelles tumeurs cutanees par patient. Les criteres secondaires etaient la proportion des patients presentant de nouvelles lesions, le nombre de lesions et leur delai d’apparition, la survenue d’autres cancers (cutanes ou non), l’evolution de la fonction renale et la tolerance de l’EV. Resultats Trente-neuf GC ont ete randomises (28 EV) de 2008 a 2012. Leurs caracteristiques a l’inclusion etaient similaires dans les 2 groupes (âge moyen 65 ans, duree d’immunosuppression 11 ans). Dix-huit patients ont eu un sevrage complet d’ACN. A 2 ans, le critere d’evaluation principal etait disponible pour 21 EV et 10 ACN. L’ensemble des patients a eu 9 CE, 14 CBC, 3 MB et 13 keratoses actiniques. En intention de traiter, l’analyse de survie sans recidive a montre une tendance en faveur de l’EV ( p = 0,073 ; HR = 0,28). En population per-protocole, neuf patients du groupe EV (42,8 %) ont developpe 26 tumeurs, contre 7 patients du groupe ACN (70 %) (13 tumeurs) dans les 2 ans apres randomisation ( p = 0,252). Le delai moyen d’apparition de la premiere tumeur n’etait pas different entre les deux groupes. La fonction renale et les effets indesirables etaient comparables dans les 2 groupes. Discussion Malgre son effectif relativement faible, lie a une insuffisance d’inclusion (22 % de l’objectif), cette etude suggere que l’introduction de l’EV chez les GC ameliore la survie sans recidive de cancer cutane, sans surcroit d’evenement indesirable sur le greffon. Les effectifs n’ont en revanche pas permis de comparer dans le groupe EV les patients ayant eu un sevrage partiel ou complet d’ACN. Conclusion L’EV apparait comme une drogue interessante pour la prevention des cancers cutanes chez les GC. Des etudes sur de plus grandes series de GC sont necessaires pour confirmer cette donnee.

Therapeutic drug monitoring of ciclosporin has been recognized as an essential tool in the management of allograft transplant recipients, as it could help improve their outcome. However, there is still no consensus about the optimal method for monitoring ciclosporin after thoracic transplantation. Better knowledge of the pharmacokinetics of ciclosporin in thoracic transplant patients and design of tools dedicated to ciclosporin monitoring could help its practice and its outcome in this population of patients. The aims of this study were to (i) investigate the population pharmacokinetics of ciclosporin in thoracic (heart or lung) transplant patients and study the influence of a range of potential covariates, including demographic, clinical and genetic factors, on pharmacokinetic parameters; and (ii) develop a Bayesian estimator able to predict the individual pharmacokinetic parameters and exposures indices in this population of patients. The analysis was performed with 187 full pharmacokinetic profiles obtained in 57 lung and 19 heart transplant patients within the first year post-transplantation. A population pharmacokinetic model was developed by non-linear mixed-effects modelling using NONMEM® (version 7.1) from an index dataset (118 profiles). On the basis of this population model and a limited number of blood samples, a Bayesian estimator able to determine ciclosporin area under the blood concentration–time curve (AUC) during a dosage interval was built and evaluated in the validation dataset (69 profiles). Ciclosporin pharmacokinetics were described using a two-compartment model with time-lagged first order absorption and first-order elimination. The final population model included sex as a covariate: ciclosporin apparent oral clearance was on average 37 % faster in male than in female patients (34.8 vs. 25.4 L/h, p

Background Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes. Methods In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 Results At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis. Conclusions In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation. Trial registration ClinicalTrials.gov NCT00159159

Coronary balloon angioplasty with stent implantation has emerged as a possible alternative to bypass grafting or repeat transplantation in left main coronary stenosis in heart transplant patients. We report 2 new cases of stent implantation for unprotected and isolated left main stenosis in heart transplant patients. Despite an initially successful procedure, restenosis prompted the performance of bypass surgery in both patients. The relative advantages and disadvantages of available techniques of revascularization are discussed in the context of the literature.

Cyclosporine (CsA) related encephalopathy has not been well documented after heart transplantation. We report 2 cases of posterior reversible encephalopathy syndrome (PRES). The first case was a 68-year-old woman who underwent heart transplantation and received immunosuppression with mycophenolate mofetil, prednisone, and CsA. On day 14, she developed arterial hypertension, headache, visual disturbances, and generalized seizures. Fluid-attenuated inversion recovery magnetic resonance imaging (MRI) of the brain showed diffuse and bilateral high signals in the frontal posterior and the occipital areas. The second case was a 19-year-old man with a heart transplant receiving immunosuppression with prednisone and CsA. On day 44, he developed acute headache and generalized seizures. T2-weighted MRI of the brain showed diffuse high signals in the cerebellum, right lenticular and occipital areas. In both cases blood CsA concentration was therapeutic. Both cases recovered but in the first case neurologic findings were reversed only after CsA withdrawal.

Previous studies have shown the capacity of low-pressure (LP) reperfusion to protect the ischemic heart. The present study sought to determine the optimal time for the application of LP reperfusion. Isolated rat hearts (n = 30) were exposed to 40 minutes of global warm ischemia followed by 70 minutes of reperfusion. Reperfusion was performed under LP (LP = 70 cm H(2)O) for 0 (control group), 5 (group LP-5), 10 (group LP-10), 30 (group LP-30), or 60 (group LP-60) minutes. Following the LP period the hearts were reperfused with normal pressure (100 cm H(2)O) until the end of reperfusion. Cardiac function was assessed during reperfusion using the Langendorff model. Myocardial necrosis was assessed by measuring LDH leakage in the coronary effluents. Functional recovery was reduced among the control and LP-5 groups with rate-pressure products (RPP) averaging 3788 +/- 499 and 5333 +/- 892 mm Hg/min, respectively. RPP was significantly improved in other groups with RPP averaging 7363 +/- 1159, 7441 +/- 863, and 7269 +/- 692 mm Hg/min in LP-10, LP-30, and LP-60 (P < .01). Similarly, necrosis measured by LDH leakage was significantly reduced in LP-10, LP-30, and LP-60 hearts (P < .01). This study demonstrated that LP reperfusion improves postischemic contractile dysfunction and attenuates necrosis when applied for at least 10 minutes.

Trichilemmal carcinoma is a rare cutaneous adnexal malignant tumor deriving from the outer root sheath of hair follicles. It is only rarely reported in recipients of solid (renal) organ transplants. We describe the first case of trichilemmal carcinoma presenting with a misleading clinical aspect in a heart transplant recipient. We then briefly outline the salient clinicopathologic features of this malignancy.

Genes involved in acute rejection (AR) after organ transplantation remain to be further elucidated. In a previous work we have demonstrated the under-expression of VE-Cadherin by endothelial cells (EC) in AR following murine and human heart transplantation. Serial sections from 15 human kidney Banff-graded transplant biopsies were examined for the presence of VE-Cadherin and CD34 staining by immunohistochemistry (no AR (n=5), AR grade IA (n=5), or AR grade IIA (n=5)). Quantification of peritubular EC staining were evaluated and results were expressed by the percentage of stained cells per surface analysed. There was no difference in CD34 staining between the 3 groups. VE-Cadherin expression was significantly reduced in AR Grade IIA when compared to no AR (P=.01) and to AR grade IA (P=.02). This study demonstrates a reduced VE-Cadherin expression by EC in AR after renal transplantation. The down-regulation of VE-Cadherin may strongly participate in human AR.

s S61 Methods: 117 patients undergoing HTx at IKEM were prospectively enrolled. AKI was defined as an increase of serum creatinine level by ≥ 50% or worsening of renal function requiring renal replacement therapy (RRT) during 1st week postHTx. Serum Cystatin-C and urinary Neutrophil gelatinase-associated lipocalin (NGAL), alpha-1-microglobulin (A1M) or albumin were serially sampled. Results: 30 patients (25.6% of total) fulfilled the criteria of AKI. Preoperative renal function, demographics and comorbidities were similar between AKI and non-AKI groups. Cystatin-C displayed earliest and the most robust separation between AKI and non-AKI group, with significant difference present already 3 hours after surgery (figure left, arrow) and persisting on day 7 and 10. The increase in Cystatin-C preceded the serum creatinine elevation by 4 days. In univariate analysis, Cystatin-C> 1.6 mg/L at 3-hours after HTx predicted AKI with OR 5.1 (95%CI: 2.2-13) and in multivariate analysis (adjustment to presence of sepsis, bleeding or need of RVAD) with OR 4.4 (95% CI:1.7-12). Urinary NGAL raised significantly only on day 3 in AKI group (p= 0.003). Differences in ACR and A1M values between groups did not reach significance. Interestingly, elevated Cystatin-C (≥ 2.5mg/L at day 7) predicted also long-term mortality after HTx (figure right). Conclusion: Cystatin-C was the most useful for evaluation and prediction of AKI. Measurement of serum Cystatin-C in patients early after HTx (3h after surgery) may help to promptly identify the patients with high risk for renal complications. Elevated cystatin-C also predicts long-term outcome. (Grant NT/11269 5 and NT/ 11262-6 and Institutional support 00023001) ascending aortic diameter was also a predictor and may reflect the risks associated with an undersized allograft. The final predictor was total ischemic time emphasizing the need for improvements in allograft preservation and storage.

The aim of the study was to analyze the etiology, the factors for progression of chronic renal failure to end-stage-renal disease (ESRD), and the influence of ESRD on the survival rate among a cohort of 59 heart transplant patients (HTP) referred for the management of chronic renal failure (CRF). At the time of the first nephrology consultation (6 +/- 4.25 years after cardiac transplantation) the mean creatininemia was 261.5 +/- 99 micromol/L and mean creatinine clearance (Cockcroft formula) was 32 +/- 15 mL/min. The cause of CRF were calcineurin inhibitor toxicity in 38.9% of patients, vascular events in 15.2%, hemolytic uremic syndrome in 5%, membranous glomerulopathy in 3.3%, diabetes in two patients, focal/segmental glomerulosclerosis in 3.3%, renal hypoplasia in 1.7%, and unknown in 27%. Evolution to ESRD occurred in 38.9% of patients: 17 patients started hemodialysis, three peritoneal dialysis, and two received a preemptive kidney transplantation. Creatininemia (micromol/L) at the time of nephrology referral was 229.2 +/- 72.6 versus 315.8 +/- 113.4 (P < .001) and creatinine clearance (mL/min) was 34.9 +/- 15.1 versus 27.3 +/- 13.7 (P = .049) for patients with CRF versus ESRD, respectively. Both proteinuria (g/24 hours) of 1 +/- 2.2 versus 2.3 +/- 1.8 (P = .02) and tobacco use in 35.1% versus 54.4% (P = .045) were significantly associated with progression of CRF, while age at the time of heart transplantation, cause of cardiac failure and renal failure, high blood pressure, type 2 diabetes, dyslipidemia, alcoholism, cirrhosis, and cerebral vascular accident were not. Death occurred in 18 HTP: 50% of patients with ESRD and 18.5% of patients with CRF-a 2.6 relative risk of of death in HTP patients with ESRD compared with HTP with CRF only (P < .01).

Background— Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. Methods and Results— Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1β (MIP-1β), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. Conclusions— We have demonstrated that the upregulation of MIP-1β and downregulation of VE-cadherin may strongly participate in human acute heart rejection.

Background Strain rate imaging (SRI), a recently developed Doppler-derived process, allows quantification of myocardial systolic function. We investigate whether SRI quantifies the contractile reserve during dobutamine stress tests in heart transplant patients (HT), when compared with normal individuals. Methods An incremental dobutamine test (5 to 40 μg/kg per minute) was performed in 10 HT and 15 control subjects, all of whom displayed normal coronary angiography. Gray-scale and color myocardial Doppler data were acquired in standard B-mode views at baseline, low-dose, peak, and recovery. Longitudinal SR was processed from the myocardial velocities for each segment. The changes in maximal systolic SR were used to quantify myocardial contractile reserve. Results Dobutamine infusion failed to induce clinical symptoms or electrocardiographic (ECG) changes in either group. Visually determined wall motion score was considered normal in all segments for each stage of the dobutamine stress. Heart rate was augmented similarly in both groups during dobutamine infusion. In controls, systolic SR increased gradually with incremental dobutamine dose and returned to baseline values upon recovery. Conversely, in HT patients, the increase in systolic SR was blunted at peak dobutamine, at which point it was significantly different vs controls. Conclusions Quantitative assessment of myocardial function using SRI during dobutamine stress revealed an impaired contractile reserve in HT patients with normal coronary angiography. These subtle changes in regional myocardial function could not be identified using visual wall motion scoring. Additional studies are necessary to evaluate whether SR imaging detection of contractile reserve impairment will improve clinical efficiency or event prediction in this population.

● Special Urgency 1 (SU1) status was granted for 48 hours, renewable once, to critically ill patients requiring continuous infusion of intravenous inotropic drugs, with or without extracorporeal membrane oxygenator or intra-aortic balloon pump support, in whom a ventricular assist device or total artificial heart were indicated and not in place and whose recovery from transplantation was likely. ● SU2 status was granted to patients requiring long-term mechanical circulatory support with device-related thromboembolism for a period of 8 days that might be renewed several times.

Introduction La prise en charge des patients presentant un syndrome cardio-renal de type 2 necessite une collaboration cardio-nephrologique et une caracterisation des patients et de leur pronostic. Patients et methodes Afin de mieux connaitre et orienter ces patients, une filiere de prise en charge des insuffisances cardiaques refractaires avec insuffisance renale a ete mise en place entre les services de cardiologie du CHU de Lyon et le service de nephrologie de l’Hopital Edouard Herriot a Lyon. Resultats Cinquante-trois patients ont ete etudies depuis janvier 2012. Le nombre moyen d’hospitalisations pour decompensations cardiaques l’annee precedente etait de 3,1. Le pourcentage de femmes etait de 30,1 %, l’âge moyen de 68 ans. La repartition des cardiopathies etait : 42 % ischemiques, 27 % dilatees, 11 % rythmiques, 8 % hypertrophiques, 8 % congenitales, 4 % restrictives. 32 % presentaient une FEVG > 50 %. Le DFG mesure (clairance de l’inuline) etait a 23 ± 14 mL/min/1,73 m2. L’albuminemie moyenne etait a 36,9 g/L, la prealbumine a 0,22 g/L. L’impedancemetrie estimait la surcharge hydrosodee moyenne a +0,25 L. Selon leur profil, les patients ont ete orientes vers la dialyse peritoneale (36 %), l’ultrafiltration par aquapherese (6 %), l’hemodialyse (24 %) et/ou une prise en charge medicale non invasive exclusive (33 %). Le projet therapeutique etait variable : optimisation en vue d’une transplantation cardiaque, amelioration du pronostic, diminution des rehospitalisations et/ou soulagement palliatif des symptomes congestifs. Parmi les patients dont le suivi date de plus de 6 mois (n = 41), la survie a 6 mois est de 61 %. Aucun deces n’a ete impute a la mise en place d’une technique d’ultrafiltration. Discussion et conclusion Les patients presentant un syndrome cardiorenal de type 2, avec une insuffisance cardiaque etiquetee refractaire, presentent des profils divers et necessitent l’elaboration d’un projet individualise et reevalue regulierement. Leur benefice a recourir aux differentes modalites d’ultrafiltration doit etre evalue, au mieux dans le cadre d’un essai controle randomise. Une evaluation a un stade plus precoce d’insuffisance cardiaque semble necessaire.

MethodsRetrospective single-centre analysis of long-term posttransplant outcome, with chart collection of clinical and paraclinical data [this study assessed the long-term outcome of heart (HTx) and heart-lung transplantation (HLTx) in patients with congenital heart disease (CHD) and children with non-congenital cardiac or pulmonary disease.]ResultsFrom 1984 to 2013, 111 first-HTx, 5 HLTx and 6 re-HTx were performed (62 males), in patients aged 11.7±8.2y: 96 (79%) aged5th year in non-compliant teenagers. Overall, 33 patients died (27%), 3.5±4.6y post-Tx (1day to 16.4y, med 1.5months), due to early multivisceral failure in 6 (18%), pulmonary hypertension in 3 (9%), acute rejection in 7 (21%), graft coronary disease in 6 (18%), sepsis in 5 (15%) and miscellaneous in 6. Graft coronary disease occurred in 15 (12.4%): 4 had re-HTx, 6 died and 5 are alive. Five lymphoma occurred, 4months to 14y after HTx, cured in 4 (1 died). Patients survival was 85% at 1y, 81% at 5y, 70% at 10y and 61% at 20y post-transplant. Graft survival rates were respectively 82%, 68% and 52% at 5y, 10y and 20y post-transplant. Survival did not differ with pretransplant disease, age, gender, pretransplant mechanical support. Mortality was higher in patients with coronary disease (40%) than those free from (25%).ConclusionLong-term prognosis after HTx and HLTx is favourable. Graft coronary disease is the main cause of failure, less frequent than in the adult non-CHD heart-transplanted population.

From 1978 to 2000, 692 patients underwent a heart transplantation (HT). 137 survived beyond the 10th year. We evaluated morbidity, mortality and immunosuppressive therapy. Population : 103 men and 34 women : Group (G) I : 10-30 y.o.(n515) G II : 30 250 y.o. (n556) GIII : 50 70 y.o. (n566). For those who had survived already 10 years, actuarial survival was 80% at 15 years following HT and 62.5% at 20 years . Mortality slope of 3%/ year was similar to the 0-to-10 year survival curve. 5 women gave birth to 7 children and 4 men had 5 kids, all healthy. Discussion : probability of surviving 20 years following HT is above 60% in this group of 10 year surviving patients. 50 % of the patients transplanted before being 50 y.o. worked after HT and 45% acknowledged no complication. Conclusion : Immunosuppression in HT patients having survived 10 years after their HT is associated with a high rate of complications relative to the low incidence of clinically relevant chronic rejection. Mortality causes (n527)

This patient was 42 years old when he had a mandible fracture treated with an intermaxillary blockage. The patient presented with endocarditis caused by Kingella denitrificans. There was a large disinsertion of both prostheses, a paravalvular abscess, and a fistula between the aorta and the right atrium. A double valvular replacement redux associated with a closure of the communication was performed. One month later, the abscess had increased, and the 2 prostheses were disinserted again (Fig 1). The hemodynamic results were unstable, and the patient was operated on for the fourth time. This reintervention (Fig 2) was done through a superior transseptal approach. 2 The 2 prostheses and all the fibrous mitro-aortic tissue, including both trigones, were removed. This huge resection, enlarged to the roof of the left atrium and to the first 3 cm of the aortic root, allowed a complete resection of the paravalvular abscess. It left a large opening on the right and left atria, the left ventricle, and the aortic root. The 2 coronary ostia were preserved in the button, and their first 2 cm were mobilized. A cryopreserved monobloc aorto-mitral homograft was prepared with a Carpentier Physio The treatment of complex valvular endocarditis remains a surgical challenge (ie, when facing a redo operation, 1 double valvular disease, or large abscess caused by aggressive bacteria). In such a situation, we propose a technique that allows a large resection of all the septic tissue and a repair by means of a cryopreserved monobloc aorto-mitral homograft. Clinical summary. A 16-year-old boy was operated on for resection of a subvalvular aortic stenosis. Two months later, postoperative endocarditis caused by Staphylococus aureus necessitated a reoperation. A mechanical bivalvular replacement was performed, and the follow-up was uneventful.

Recent work has demonstrated the benefit of low pressure (LP) reperfusion to protect the heart undergoing an ischemic insult. The goal of the present study was to determine the optimal pressure for the application of LP reperfusion. Isolated rats hearts (n = 30) were exposed to 40 minutes of global warm ischemia followed by 70 minutes of reperfusion with a pressure fixed at 100 cm H(2)O (normal pressure [NP] = control group), 85 cm (group LP [low pressure]-85), 70 cm (group LP-70), or 55 cm (group LP-55). Cardiac function was assessed during reperfusion using the Langendorff model. Myocardial necrosis was assessed by measuring lactate dehydrogenase (LDH) and creatine kinase (CK) leakage in the coronary effluents. Functional recovery was progressively and significantly improved with decreased perfusion pressure. Rate-pressure product (RPP) averaged 3765 +/- 408, 6824 +/- 439, and 12,036 +/- 664 mm Hg/min, respectively, among the control, LP-85, and LP-70 groups (P < .001, LP-70 vs other groups). However, RPP collapsed in the LP-55 group. Similarly, necrosis as measured by LDH and CK leakage progressively reduced between LP-100 and LP-70 hearts (P < .01), with a drastic increase in enzyme in the LP-55 group. In conclusion, this study demonstrated that 70 cm H(2)O is an optimal LP to improve postischemic contractile dysfunction and attenuate necrosis during reperfusion.

The cardioprotective effect of ischemic preconditioning has been hypothesized to occur through one or more signalling mechanisms which activate protein kinase C. Stimulation of alpha 1-adrenergic receptors by catecholamines released during the preconditioning episodes of ischemia is one of these putative signalling mechanisms.To determine whether stimulation of alpha 1-adrenergic receptors before an ischemic challenge can mimic preconditioning, anesthetized dogs were treated with 4 intracoronary infusions of methoxamine HCl (10 micrograms/kg/min; n = 8), each 5 min in duration and followed by 5 min of washout. Control dogs (n = 10) were given similar infusions of 0.9% NaCl. A third group of dogs was preconditioned with 4 cycles of 5 min ischemia, each followed by 5 min of reperfusion (n = 8). All dogs then underwent 60 min of ischemia (circumflex coronary occlusion) followed by 3 h of reperfusion. Infarct size (expressed as % of area-at-risk) was measured with TTC macrochemistery and analyzed (using analysis of covariance [ANCOVA]) with respect to coronary collateral blood flow (measured using radioactive microspheres).Methoxamine markedly increased systemic arterial and left atrial pressures prior to but not during the ischemic challenge. Baseline predictors of infarct size were not different among the groups. Mean infarct size (adjusted from ANCOVA) did not differ between control and methoxamine-treated groups, 28.3 +/- 2.8% vs. 29.7 +/- 3.2%, respectively (P = NS), but was only 12.7 +/- 3.2% in the preconditioned group (P0.01 vs. control and methoxamine).A series of methoxamine infusions before an ischemic challenge did not affect infarct size. Thus, stimulation of alpha 1-adrenergic receptors alone is insufficient to mimic the cardioprotective effect of ischemic preconditioning in this canine model.