IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition.

Expansion of CD4+CD28null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4+CD28null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4+CD28null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4+CD28null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4+CD28null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4+CD28null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4+CD28null T-lymphocytes.

Incidence and Prognosis of Colorectal Cancer After Heart Transplantation: Data From the Spanish Post-Heart Transplant Tumor Registry.

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

Utility of the IMPACT score for predicting heart transplant mortality. Analysis on a contemporary cohort of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. METHODS: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). RESULTS: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. CONCLUSIONS: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

Malignancy following heart transplantation: differences in incidence and prognosis between sexes - a multicenter cohort study.

Male patients are at increased risk for developing malignancy postheart transplantation (HT); however, real incidence and prognosis in both genders remain unknown. The aim of this study was to assess differences in incidence and mortality related to malignancy between genders in a large cohort of HT patients. Incidence and mortality rates were calculated for all tumors, skin cancers (SCs), lymphoma, and nonskin solid cancers (NSSCs) as well as survival since first diagnosis of neoplasia. 5865 patients (81.6% male) were included. Total incidence rates for all tumors, SCs, and NSSCs were lower in females [all tumors: 25.7 vs. 44.8 per 1000 person-years; rate ratio (RR) 0.68, (0.60-0.78), P < 0.001]. Mortality rates were also lower in females for all tumors [94.0 (77.3-114.3) vs. 129.6 (120.9-138.9) per 1000 person-years; RR 0.76, (0.62-0.94), P = 0.01] and for NSSCs [125.0 (95.2-164.0) vs 234.7 (214.0-257.5) per 1000 person-years; RR 0.60 (0.44-0.80), P = 0.001], albeit not for SCs or lymphoma. Female sex was associated with a better survival after diagnosis of malignancy [log-rank p test = 0.0037; HR 0.74 (0.60-0.91), P = 0.004]. In conclusion, incidence of malignancies post-HT is higher in males than in females, especially for SCs and NSSCs. Prognosis after cancer diagnosis is also worse in males.

Gender differences in heart transplantation: Twenty-five year trends in the nationwide Spanish heart transplant registry.

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993-2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25-year study period. HT rate was higher in men, although this decreased over the 25-year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre-HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality-related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001).

Impact of mechanical circulatory support on survival in pediatric heart transplantation.

Evidence on the impact of MCS on pediatric heart transplant survival is still scarce related to congenital heart disease patients including univentricular physiology as well as the risk factors for complications. We performed a retrospective review of all urgent pediatric (aged ≤16 years) HT from 2004 to 2014 in the Spanish Pediatric Heart Transplant Registry Group. Patients were stratified into two groups: urgent 0 (MCS at HT) and urgent 1 (non-MCS at HT). The primary outcome measure was post-transplant survival; secondary outcome measures were complications and absence of infections and rejection during the first post-transplant year. One hundred twenty-one pediatric patients underwent urgent HT, 58 (47.9%) urgent 0 and 63 (52%) urgent 1. There were 30 (24.8%) deaths: 12 in the urgent 0 group and 18 in the urgent 1 group, P = n.s. Regarding the type of MCS, patients on ECMO had the highest rate of complications (80%) and mortality (40%). Patients in the urgent 1 group showed a higher risk of hospital re-admission for infection during the first year after transplantation (OR 2.31 [1.1-4.82]), P = .025. We did not identify a risk factor for mortality. MCS does not impact negatively on survival after HT. However, there is a significant increase in 30-day and 1-year mortality and complications in ECMO patients compared with VAD patients. Infants, congenital heart disease, and PediMACS were not found to be risk factors for mortality.

Use of Idarucizumab to reverse the anticoagulant effect of dabigatran in cardiac transplant surgery. A multicentric experience in Spain.

BACKGROUND: Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non-valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab. AIM: To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT. METHODS: Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery. RESULTS: Fifty-three patients were included (81.1% male). 7.5% required re-operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30-day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post-HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post-HT death was associated with bleeding. CONCLUSIONS: These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.

More intensive CMV-infection in chronic heart failure patients contributes to higher T-lymphocyte differentiation degree.

Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC). High differentiation of CD8+ T-lymphocytes was found in CMV-seropositive patients; however, the differentiation of CD4+ T-lymphocytes was increased in CMV-seropositive but also in CHF patients. Anti-CMV antibody titers showed positive correlation with more differentiated CD4+ and CD8+ subsets and inverse correlation with CD4/CD8 ratio. Immunosenescence found in CHF patients is mainly due to the dynamics of CMV-infection, since the differentiation of T-lymphocyte subsets is related not only to CMV-infection, but also to anti-CMV antibody titers.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.

Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis.

INTRODUCTION AND OBJECTIVES: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. METHODS: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). RESULTS: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). CONCLUSIONS: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality.

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.

Review of the allocation criteria for heart transplant in Spain in 2023. SEC-Heart Failure Association/ONT/SECCE consensus document.

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation.

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.

Opportunistic Genetic Screening for Familial Hypercholesterolemia in Heart Transplant Patients.

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T>C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C>T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A>G and c.5600G>A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered.

Optical coherence tomography assessment of pulmonary vascular remodeling in advanced heart failure. The OCTOPUS-CHF study.

INTRODUCTION AND OBJECTIVES: Pulmonary vascular remodeling is common among patients with advanced heart failure. Right heart catheterization is the gold standard to assess pulmonary hypertension, but is limited by indirect measurement assumptions, a steady-flow view, load-dependency, and interpretation variability. We aimed to assess pulmonary vascular remodeling with intravascular optical coherence tomography (OCT) and to study its correlation with hemodynamic data. METHODS: This observational, prospective, multicenter study recruited 100 patients with advanced heart failure referred for heart transplant evaluation. All patients underwent right heart catheterization together with OCT evaluation of a subsegmentary pulmonary artery. RESULTS: OCT could be performed and properly analyzed in 90 patients. Median age was 57.50 [interquartile range, 48.75-63.25] years and 71 (78.88%) were men. The most frequent underlying heart condition was nonischemic dilated cardiomyopathy (33 patients [36.66%]). Vascular wall thickness significantly correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient (R coefficient=0.42, 0.27 and 0.32 respectively). Noninvasive estimation of pulmonary artery systolic pressure, acceleration time, and right ventricle-pulmonary artery coupling also correlated with wall thickness (R coefficient of 0.42, 0.27 and 0.49, respectively). Patients with a wall thickness over 0.25mm had significantly higher mean pulmonary pressures (37.00 vs 25.00mmHg; P=.004) and pulmonary vascular resistance (3.44 vs 2.08 WU; P=.017). CONCLUSIONS: Direct morphological assessment of pulmonary vascular remodeling with OCT is feasible and is significantly associated with classic hemodynamic parameters. This weak association suggests that structural remodeling does not fully explain pulmonary hypertension.

Mechanical circulatory support in severe primary graft dysfunction: Peripheral cannulation but not earlier implantation improves survival in heart transplantation.

BACKGROUND: Primary graft dysfunction (PGD) still affects 2% to 28% of heart transplants (HT). Severe PGD requires mechanical circulatory support (MCS) and is the main cause of death early after HT. Earlier initiation has been suggested to improve prognosis but the best cannulation strategy is unknown. METHODS: Analysis of all HT in Spain between 2010 and 2020. Early (<3 hours after HT) vs late initiation (≥3 hours after HT) of MCS was compared. Special focus was placed on peripheral vs central cannulation strategy. RESULTS: A total of 2376 HT were analyzed. 242 (10.2%) suffered severe PGD, 171 (70.7%) received early MCS and 71 (29.3%) late MCS. Baseline characteristics were similar. Patients with late MCS had higher inotropic scores and worse renal function at the moment of cannulation. Early MCS had longer cardiopulmonary bypass times and late MCS was associated with more peripheral vascular damage. No significant differences in survival were observed between early and late implant at 3 months (43.82% vs 48.26%; log-rank p = 0.59) or at 1 year (39.29% vs 45.24%, log-rank p = 0.49). Multivariate analysis did not show significant differences favoring early implant. Survival was higher in peripheral compared to central cannulation at 3 months (52.74% vs 32.42%, log-rank p = 0.001) and 1 year (48.56% vs 28.19%, log-rank p = 0.0007). In the multivariate analysis, peripheral cannulation remained a protective factor. CONCLUSIONS: Earlier MCS initiation for PGD was not superior, compared to a more conservative approach with deferred initiation. Peripheral compared to central cannulation showed superior 3-month and 1-year survival rates.

Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry.

INTRODUCTION AND OBJECTIVES: This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. METHODS: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. RESULTS: During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). CONCLUSIONS: Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

Association between a common KCNJ11 polymorphism (rs5219) and new-onset posttransplant diabetes in patients treated with Tacrolimus.

KCNJ11 polymorphisms have been linked to the risk of developing type 2 diabetes. Our aim was to define the contribution of KCNJ11 to new-onset diabetes after transplantation (NODAT) among patients treated with Tacrolimus (Tac). A total of 115 NODAT and 205 non-NODAT were genotyped for rs5219 (p.E23K). AA+AG genotypes were significantly associated with NODAT-risk (p=0.004; OR=2.10). The reported effect of this KCNJ11 polymorphism on insulin release by beta cells could explain this association.

Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes.

INTRODUCTION AND OBJECTIVES: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. METHODS: We retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. RESULTS: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. CONCLUSIONS: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients.