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.

Results of heart retransplantation: subanalysis of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: Heart retransplantation (ReHT) is controversial in the current era. The aim of this study was to describe and analyze the results of ReHT in Spain. METHODS: We performed a retrospective cohort analysis from the Spanish Heart Transplant Registry from 1984 to 2018. Data were collected on donors, recipients, surgical procedure characteristics, immunosuppression, and survival. The main outcome was posttransplant all-cause mortality or need for ReHT. We studied differences in survival according to indication for ReHT, the time interval between transplants and era of ReHT. RESULTS: A total of 7592 heart transplants (HT) and 173 (2.3%) ReHT were studied (median age, 52.0 and 55.0 years, respectively). Cardiac allograft vasculopathy was the most frequent indication for ReHT (42.2%) and 59 patients (80.8%) received ReHT >5 years after the initial transplant. Acute rejection and primary graft failure decreased as indications over the study period. Renal dysfunction, hypertension, need for mechanical ventilation or intra-aortic balloon pump and longer cold ischemia time were more frequent in ReHT. Median follow-up for ReHT was 5.8 years. ReHT had worse survival than HT (weighted HR, 1.43; 95%CI, 1.17-1.44; P<.001). The indication of acute rejection (HR, 2.49; 95%CI, 1.45-4.27; P<.001) was related to the worst outcome. ReHT beyond 5 years after initial HT portended similar results as primary HT (weighted HR, 1.14; 95%CI, 0.86-1.50; P<.001). CONCLUSIONS: ReHT was associated with higher mortality than HT, especially when indicated for acute rejection. ReHT beyond 5 years had a similar prognosis to primary HT.

Impact of donor-recipient age on cardiac transplant survival. Subanalysis of the Spanish Heart Transplant Registry.

INTRODUCTION AND OBJECTIVES: The age of heart transplant recipients and donors is progressively increasing. It is likely that not all donor-recipient age combinations have the same impact on mortality. The objective of this work was to compare survival in transplant recipients according to donor-recipient age combinations. METHODS: We performed a retrospective analysis of transplants performed between 1 January 1993 and 31 December 2017 in the Spanish Heart Transplant Registry. Pediatric transplants, retransplants and combined transplants were excluded (6505 transplants included). Four groups were considered: a) donor <50 years for recipient <65 years; b) donor <50 years for recipient ≥ 65 years; c) donor ≥ 50 years for recipient ≥ 65 years, and d) donor ≥ 50 years for recipient <65 years. RESULTS: The most frequent group was young donor for young recipient (73%). There were differences in the median survival between the groups (P <.001): a) younger-younger: 12.1 years, 95%CI, 11.5-12.6; b) younger-older: 9.1 years, 95%CI, 8.0-10.5; c) older-older: 7.5 years, 95%CI, 2.8-11.0; d) older-younger: 10.5 years, 95%CI, 9.6-12.1. On multivariate analysis, independent predictors of mortality were the age of the donor and the recipient (0.008 and 0.001, respectively). The worst combinations were older-older vs younger-younger (HR, 1.57; 95%CI, 1.22-2.01; P <.001) and younger-older vs younger-younger (HR, 1.33; 95%CI, 1.12-1.58; P=.001). CONCLUSIONS: Age (of the donor and recipient) is a relevant prognostic factor in heart transplant. The donor-recipient age combination has prognostic implications that should be identified when accepting an organ for transplant.

Spanish Heart Transplant Registry. 31th Official Report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. METHODS: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. RESULTS: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P=.34). Survival in both these periods was better than that from 2010 to 2012 (P=.002 and P=.01, respectively). CONCLUSIONS: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Spanish Heart Transplant Registry. 30th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure (1984-2018).

INTRODUCTION AND OBJECTIVES: The present report updates the clinical characteristics and outcomes of heart transplant in Spain to 2018. METHODS: Prospective registry of all the heart transplants performed between 1984 and 2018 in Spain. Specifically, temporal trends in clinical characteristics and outcomes are described for the period from 2009 to 2017. RESULTS: In 2018, 321 transplants were performed (8494 since 1984; 2719 between 2009 and 2018). Compared with the previous year, the number of transplants performed in 2018 rose by 52% in recipients younger than 16 years and by 42% in those older than 60 years. In the last decade, significant temporal trends were observed in recipient characteristics (better pretransplant renal function, higher rates of diabetes, more urgent transplants, and greater use of pretrasplant circulatory support, particularly ventricular assist devices), donor characteristics (higher donor age, more female donors, and higher frequencies of cerebrovascular cause of death and predonation cardiac arrest and lower ischemia time). Survival significantly improved in the last decade, mainly due to lower mortality due to primary graft failure. CONCLUSIONS: The number of heart transplants is increasing in Spain, with a progressive improvement in survival.

Spanish Heart Transplant Registry. 29th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure.

INTRODUCTION AND OBJECTIVES: The present report updates the characteristics and results of heart transplantation in Spain, mainly focused in the 2008-2017 period. METHODS: We describe the recipient and donor characteristics, surgical procedures, and outcomes of heart transplants performed in 2017. The 2017 data were compared with those obtained from 2008 to 2016. RESULTS: A total of 304 cardiac transplants were performed in 2017. Between 1984 and 2017, 8173 procedures were performed, 2689 of them after 2008. Significant temporal trends were observed in recipient characteristics (lower pulmonary vascular resistance, lower use of mechanical ventilation, and a higher percentage of diabetic patients and those with previous cardiac surgery), donor characteristics (older donor age and a higher percentage of female donors and those with a prior cardiac arrest) and procedures (lower ischemia time). In 2017, 27% of patients were transplanted after undergoing mechanical ventricular assistance (P <.001 for trend). In the last decade, there was a trend to better survival. CONCLUSIONS: Around 300 transplants per year were performed in Spain in the last decade. There was a significant increase in the use of pretransplant mechanical circulatory support and a trend to improved survival.

[Effects of three different disease management programs on outcomes in patients hospitalized with heart failure: a randomized trial]. / Efectos sobre la mortalidad y reingresos hospitalarios de tres tipos distintos de programas de intervención en pacientes hospitalizados por insuficiencia cardiaca: ensayo clínico aleatorizado.

BACKGROUND AND OBJECTIVE: Despite the recognized benefit of intervention programs in patients with heart failure (HF), it is unknown whether different types of programs have similar efficacy. The aim of our study was to compare the effectiveness of three different types of intervention. PATIENTS AND METHODS: 208 patients discharged with the diagnosis of HF were randomized. Fifty-two were assigned to each one of different groups of intervention (home visits, telephone follow-up, HF unit) and 52 patients to usual care (control group). RESULTS: Median follow-up was 10.8±3.2 months. During the study, the primary end point (HF hospitalization or death) was reached in: 20 patients (38.5%) in control group, 19 (36.5%) in telephone follow-up (HR 1.11; IC95% [0.59-2.01], p=0.79), 24 (46.2%) in home visits (HR 1.27; IC95% [0.69-2.32], p=0.78) and 23 patients (44.2%) in HF unit (HR 1.33; IC95% [0.73-0.42], p=0.79). There was a trend to higher hospitalizations (shorter) with lower mortality in intervention groups (mortality: 23.1% intervention groups vs 33.3% in control group, HR 0.61 IC al 95% [0.35-1.01], p=0.08). CONCLUSIONS: In our study, the application of three different intervention programs in patients with HF has a little non-significant prognosis benefit, with a slight increase in the number of shorts hospitalizations in HF unit.

Withdrawal of proliferation signal inhibitors due to adverse events in the maintenance phase of heart transplantation.

BACKGROUND: The increasing use of proliferation signal inhibitors (PSIs) has raised the issue of their risk profile. We sought to determine the causes, incidence, risk factors, and consequences of withdrawal due to adverse events of PSIs in maintenance heart transplantation. METHODS: This was a retrospective study from 9 centers of the Spanish Registry for Heart Transplantation. Demographic, clinical, analytic, and evolution data were obtained for patients in whom a PSI (sirolimus or everolimus) was used between October 2001 and March 2009. RESULTS: In the first year, 16% of 548 patients could not tolerate PSIs. This incidence rate stabilized to 3% to 4% per year thereafter. The most frequent causes for discontinuation were edema (4.7%), gastrointestinal toxicity (3.8%), pneumonitis (3.3%), and hematologic toxicity (2.0%). In multivariate analysis, withdrawal of PSI was related to the absence of statin therapy (p = 0.006), concomitant treatment with anti-metabolites (p = 0.006), a poor baseline renal function (p = 0.026), and multiple indications for PSI use (p = 0.04). Drug discontinuation was associated with a decline in renal function (p = 0.045) but not with an excess in mortality (p = 0.42). CONCLUSIONS: In this large cohort of maintenance heart transplant recipients taking a PSI, 16% withdrew treatment in the first year, and 25% had stopped PSI due to severe adverse events by the fourth year. This high rate of toxicity-related PSI withdrawal could limit the clinical utility of this otherwise novel class of immunosuppressive agents.

Perceived influence of oral health upon quality of life in heart transplant patients.

OBJECTIVE: A study was made of heart transplant patient perception of the influence of oral health upon quality of life, based on the Oral Health Impact Profile (OHIP-49) questionnaire validated for Spanish speaking subjects. DESIGN: A cross-sectional evaluation was made of the heart transplant patients followed-up on in the Heart Transplantation Unit of Reina Sofía University Hospital (Spain), using the OHIP-49 questionnaire. The included patients were all over age 18 and signed the corresponding informed consent to participation in the study. The data were entered in a database and analyzed using the SPSS statistical package. RESULTS: A total of 150 heart transplant patients (118 males and 32 females, with a mean age of 54.94 years; range 19-79) were studied. The subjects showed a poor perceived influence of oral health upon quality of life, with a mean score of 24.43 out of a possible total of 196 points. Women showed significantly improved perception of the influence of oral health upon quality of life versus men. CONCLUSIONS: The subjects in our study showed a poor perceived influence of oral health upon quality of life.

Anticoagulación en pacientes menores de 75 años con fibrilación auricular / Anticoagulation in patients aged less than 75 years with atrial fibrillation

Para estudiar la efectividad y seguridad de la anticoagulación en la fibrilación auricular no valvular crónica en pacientes menores de 75 años de la práctica clínica diaria incluimos en un estudio prospectivo 345 pacientes consecutivos atendidos entre el 1 de febrero de 2000 y el 1 de febrero de 2002 en dos consultas de cardiología. Se les indicó tratamiento anticoagulante de acuerdo con las recomendaciones de las sociedades científicas y fueron seguidos para evaluar eventos mayores (muerte, ictus, accidente isquémico transitorio, embolismos periféricos o hemorragia grave) por grupo de tratamiento. Los pacientes con terapia anticoagulante (n = 262,76%) presentaron una mayor frecuencia de hipertensión y embolismo previo y un mayor número de factores de riesgo cardioembólicos (p < 0.001); el 92% de los pacientes tratados sin anticoagulantes recibieron antiagregantes. Tras 23 ± 13 meses de seguimiento, la tasa (por 100 pacientes-año) de eventos embólicos (0.82 versus3.42, p = 0.022) fue menor en los pacientes que recibieron anticoagulantes, sin diferencias significativas en las tasas de sangrado grave (0.61 frente a 1.37, p = 0.39), ni en la mortalidad total (1.23 frente a 1.37, p = 0.96). La anticoagulación oral en la fibrilación auricular no valvular de aucerdo con las recomendaciones de las sociedades científicas es efectiva y segura en pacientes menores de 75 años en la práctica clínica diaria.

Our objective was to study the effectiveness and safety of oral anticoagulation for permanent non-valvular atrial fibrillation in patients younger than 75 years seen in dailyclinical practice. In a prospective study, we included 345 consecutive patients seen since February, 1st 2000 toFebruary 1st 2002 in two outpatient cardiology clinics. Anticoagulant treatment was indicated following scientific societies recommendations; and patients were divided intreatment groups and followed for major events (death,stroke, transient ischemic attack, peripheral embolism orsevere haemorrhage). Anticoagulated patients (n = 262,76%) presented hypertension and previous embolism more frequently; as well as a greater number of cardioembolicrisk factors (p < 0.001). Ninety-two percent ofnon-anticoagulated patients received platelet aggregation inhibitors. After 23 ± 13 months of follow-up, the rateof embolic events (per 100 patients-year) was lower inanticoagulated patients (0.82 versus 3.42, p = 0.022). Rates of severe bleeding (0.61 versus 1.37, p = 0.39) andall-cause mortality (1.23 versus 1.37, p = 0.96) showed no significant differences. Oral anticoagulation in nonvalvularatrial fibrillation following the recommendationsof scientific societies is effective and safe in patients younger than 75 years in daily clinical practice.