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To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes.Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years.Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population.Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.

Resumen Introduccion y objetivos Analizar la supervivencia de los pacientes con insuficiencia cardiaca (IC) tratados en una unidad especializada. Metodos Estudio prospectivo de una cohorte de pacientes con IC tratados en una unidad especializada entre 2011 y 2017. Se comparo la mortalidad observada a 1 y 3 anos con la mortalidad pronosticada por la puntuacion de riesgo del Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC). Resultados Se estudio a 1.280 pacientes, con una mediana de la puntuacion MAGGIC de 19 [intervalo intercuartilico, 13-24]. Las tasas de prescripcion de bloqueadores beta, inhibidores de la enzima de conversion de la angiotensina, antagonistas del receptor de la angiotensina II, antagonistas del receptor de mineralcorticoides y sacubitrilo-valsartan fueron del 93, el 67, el 22, el 73 y el 16% respectivamente. La puntuacion MAGGIC mostro una discriminacion adecuada de la mortalidad a 1 ano (estadistico c = 0,71) y a 3 anos (estadistico c = 0,76). La mortalidad observada fue significativamente menor que la pronosticada, tanto a 1 ano (el 6,2 frente al 10,9%; cociente observada/pronosticada = 0,57; p 40% (el 19,6 frente al 20,7%; cociente observada/pronosticada = 0,95; p = 0,640). Conclusiones Los pacientes con IC tratados en una unidad especializada presentaron una mortalidad inferior a la pronosticada por la puntuacion MAGGIC.

Resumen Introduccion y objetivos Analizar el impacto pronostico de la infeccion por citomegalovirus (CMV) durante el primer ano tras el trasplante cardiaco (TC) y describir factores de riesgo. Metodos Se realizo un estudio retrospectivo unicentrico que incluyo 222 receptores de TC. La identificacion de factores de riesgo de infeccion por CMV se llevo a cabo mediante la regresion multivariable de Cox. A traves de los metodos de Kaplan-Meier y Cox se analizo la influencia de la infeccion por CMV durante el primer ano sobre la supervivencia e incidencia de eventos clinicos adversos en el seguimiento a largo plazo. Resultados En el analisis multivariante, el estado serologico donante/receptor frente a CMV (hazard ratio [HR] 1,92, intervalo de confianza 95% [IC 95%] 1,2-3,09; p = 0,007), la edad del receptor (HR 1,02, IC 95%: 1,00-1,1; p = 0,02), la diabetes (HR 1,86, IC 95%: 1,4-3,05; p = 0,01), el soporte circulatorio mecanico (HR 1,59, IC 95%: 1,06-2,38; p = 0,03) y el uso de tacrolimus (HR 1,64, IC 95%: 1,13-2,36; p = 0,009) resultaron predictores independientes de infeccion por CMV postrasplante. No se detecto una influencia significativa de la infeccion por CMV durante el primer ano postrasplante sobre la mortalidad, la incidencia de insuficiencia cardiaca, enfermedad vascular del injerto o rechazo agudo. Conclusiones La infeccion por CMV durante el primer ano postrasplante no se asocio a un peor pronostico a largo plazo.

Observational study [Abstract] Aims: To assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF). Methods: Observational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory. Results: We studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4-2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1-4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1-1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8-3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26). Conclusion: Patients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population.

Resumen Introduccion y objetivos Los valores plasmaticos de galectina-3 (Gal-3) estan elevados y se correlacionan con la mortalidad total y cardiovascular en pacientes con insuficiencia cardiaca, pero su correlacion con el pronostico tras el trasplante cardiaco (TxC) es desconocida. El objetivo fue describir la tendencia evolutiva y el valor pronostico de este biomarcador tras el TxC. Metodos Mediante enzimoinmunoensayo, se midieron las concentraciones plasmaticas de Gal-3 en muestras de suero de 122 receptores de TxC, antes y 1, 3, 6 y 12 meses despues de este. Mediante regresion de Cox se analizo el valor pronostico del valor plasmatico de Gal-3 a los 12 meses del TxC. El objetivo primario del estudio fue la variable combinada muerte o disfuncion del injerto. Resultados Las concentraciones de Gal-3 disminuyeron progresivamente durante el primer ano tras el TxC (medianas: pretrasplante, 19,1 ng/ml; 1 ano postrasplante, 14,6 ng/ml; p Conclusiones Las concentraciones plasmaticas de Gal-3 disminuyeron progresivamente durante el primer ano tras el TxC. Un valor plasmatico elevado de Gal-3 1 ano tras el TxC se correlaciono con un pronostico adverso.

[Abstract] Introduction and objectives: Circulating galectin-3 (Gal-3) is elevated and significantly correlates with all-cause and cardiovascular mortality in patients with heart failure. However, the relationship between serum Gal-3 and heart transplant (HT) outcomes is unclear. The aim of this study was to describe the longitudinal trend and prognostic value of Gal-3 levels after HT. Methods: Banked serum samples were available from 122 HT recipients, collected before transplant and at 1, 3, 6, and 12 months posttransplant. Gal-3 levels in these serum samples were measured by enzyme immune assay. Multivariable Cox regression was performed to determine the prognostic value of 12-month posttransplant Gal-3 serum levels. The primary endpoint was the composite variable all-cause death or graft failure over long-term posttransplant follow-up. Results: Circulating Gal-3 concentration steadily decreased during the first year after HT (median values: pretransplant, 19.1 ng/mL; 1-year posttransplant, 14.6 ng/mL; P

[Abstract] Aims Maximum oxygen uptake (VO₂max) is an essential parameter to assess functional capacity of patients with heart failure (HF). We aimed to identify clinical factors that determine its value, as they have not been well characterized yet. Methods We conducted a retrospective, observational, single‐centre study of 362 consecutive patients with HF who underwent cardiopulmonary exercise testing (CPET) as part of standard clinical assessment since 2009–2019. CPET was performed on treadmill, according to Bruce's protocol (n = 360) or Naughton's protocol (n = 2). We performed multivariable linear regression analyses in order to identify independent clinical predictors associated with peak VO₂max. Results Mean age of study patients was 57.3 ± 10.9 years, mean left ventricular ejection fraction was 32.8 ± 14.2%, and mean VO₂max was 19.8 ± 5.2 mL/kg/min. Eighty‐nine (24.6%) patients were women, and 114 (31.5%) had ischaemic heart disease. Multivariable linear regression analysis identified six independent clinical predictors of VO₂max, including NYHA class (B coefficient = −2.585; P < 0.001), age (B coefficient per 1 year = −0.104; P < 0.001), tricuspid annulus plane systolic excursion (B coefficient per 1 mm = +0.209; P < 0.001), body mass index (B coefficient per 1 kg/m² = −0.172; P = 0.002), haemoglobin (B coefficient per 1 g/dL = +0.418; P = 0.007) and NT‐proBNP (B coefficient per 1000 pg/mL = −0.142; P = 0.019). Conclusions The severity of HF (NYHA class, NT‐proBNP) as well as age, body composition and haemoglobin levels influence significantly exercise capacity. In patients with HF, the right ventricular systolic function is of greater importance for the physical capacity than the left ventricular systolic function. This work was supported by FEDER Funds, Instituto de Salud Carlos III, Madrid

[Abstract] Introduction and objectives. To assess the risk factors of CMV infection after heart transplant (HT) and its influence on long-term prognosis. Methods. We conducted a retrospective single-centre study of 222 H T recipients. Risk factors for CMV infection were identified by means of multivariable Cox´s regression. Kaplan-Meier analysis and Cox´s regression were used to assess the long-term prognostic impact of CMV infection during the first post-transplant year. Results. Donor-recipient CMV serologic matching (hazard ratio [HR] 1.92, 95% confidence interval [95% CI] 1.2–3.09, p = .007), recipient age (HR 1.02, 95% CI 1.00–1.1, p = .02), diabetes mellitus (HR 1.86, 95% CI 1.4–3.05, p = .01), pre- transplant circulatory support (HR 1.59, 95% CI 1.06–2.38, p = .03) and the use of tacrolimus (HR 1.64, 95% CI 1.13–2.36, p = .009) were independently associated with increased risk of CMV infection. CMV infection during the first year post-HT was not associated with worse transplant outcomes in terms of mortality, incidence of heart failure, cardiac allograft vasculopathy or acute rejection. Conclusions. CMV infection was not associated with impaired long-term prognosis after HT. [Resumen] Introducción y objetivos. Analizar el impacto pronóstico de la infección por Citomegalovirus (CMV) durante el primer año tras el trasplante cardiaco (TC) y describir factores de riesgo. Métodos. Se realizó un estudio retrospectivo unicéntrico incluyendo 222 receptores de TC. La identificación de factores de riesgo de infección por CMV se llevó a cabo mediante regresión multivariable de Cox. Mediante los métodos de Kaplan-Meier y Cox se analizó la influencia de la infección por CMV durante el primer año sobre la supervivencia e incidencia de eventos clínicos adversos en el seguimiento a largo plazo. Resultados. En el análisis multivariante, el estado serológico donante/receptor frente a CMV (hazard ratio [HR] 1,92, intervalo de confianza 95% [IC 95%] 1,2–3,09; p = 0007, la edad del receptor HR 1,02, IC 95% 1,00–1,1; p = 0,02), la diabetes (HR 1,86, IC 95% 1,4-3,05; p = 0,01), el soporte circulatorio mecánico (HR 1,59, IC 95% 1,06-2,38; p = 0,03) y el uso de tacrolimus (HR 1,64, IC 95% 1,13-2,36; p = 0009, resultaron predictores independientes de infección por CMV post-trasplante. No se detectó una influencia significativa de la infección por CMV durante el primer año post-trasplante sobre la mortalidad, la incidencia de insuficiencia cardiaca, enfermedad vascular del injerto o rechazo agudo. Conclusiones. La infección por CMV durante el primer año post-trasplante no se asoció a un peor pronóstico a largo plazo.

Background Acute Cellular Rejection (ACR) remains a major complication in heart transplantation (HT). Since 1970, endomyocardial biopsy (EMB) has been the gold standard for ACR early detection. However, this invasive procedure has several limitations such as risk of complications, interobserver variability, false negative results and high cost. Therefore, a new non-invasive ACR biomarker is needed. Potential candidates could be microRNAs (miRs), small regulatory RNAs whose serum expression profiling could be modified in ACR patients. The aim of this study is the identification of differentially serum miRs expression patterns in ACR after HT. Methods Among HT performed in our Hospital (2013–2018), we selected patients with following criteria: i) “0R → 2R → 0R” EMB pattern for ACR (0R=no ACR, 2R=moderate ACR); ii) no antibody mediated rejection; iii) serum collected the same day as the EMBs. The 3 serum samples per patient matched in time with EMB were called “0Rs1 → 2Rs2 → 0Rs3”. In each of these serum samples, 179 miRs expression profile according manufacturer's instructions were analysed. Global Mean (GM) method was used to normalize our results expressed as miRs relative expression [2(–ΔCq)]. Expression pattern was defined as a 2 steps process: a significative rise (0Rs1 → 2Rs2) followed by a significative fall (2Rs2 → 0Rs3), or vice versa, in miR expression. Analysis of differences between 3 groups were calculated using one-way ANOVA with matched data and post-hoc Tukey test. ROC curve was generated for selected miRNA. A two-sided p Results 21 patients and their serum “0Rs1 → 2Rs2 → 0Rs3” samples were included in the study. Among 179 miRs analysed, 5 miRs showed significative difference between 0Rs1 and 2Rs2, 3 miRs were over-expressed (miR-181a-5p, miR-339-3p, let-7f-5p) and 2 under-expressed (miR-505-3p, miR-2110). Only miR-181a-5p met significative difference between 2Rs2 and 0Rs3 showing a statistical significative rise/fall pattern. Serum miR-181a-5p ROC analysis demonstrated significant discrimination between biopsy proven ACR from no-ACR biopsy, AUC=0.692 (p=0.0335). Differentially expressed miRs Mean relative expression 2(–ΔCq) (95% CI) Adjusted p-value (ANOVA) AUC (95% CI) 0Rs1 2Rs2 0Rs3 0Rs1 vs 2Rs2 2Rs2 vs 0Rs3 0Rs1 vs 0Rs3 miR-181–5p 0.80 (0.60–1.02) 1.11 (0.90–1.31) 0.86 (0.71–1.01) 0.0194 0.0225 NS 0.692 (0.529–0,855) Relative Expression 2(–ΔCq) and AUC expressed as mean (95% Confident Interval). NS: not significative. Conclusion Our findings suggest miR-181a-5p as a novel serological biomarker for detecting ACR after HT. After this preliminary discovery phase, miR-181a-5p is currently in a new validation phase to demonstrate its diagnostic performance. Acknowledgement/Funding This work was supported by a grant from isciii (PI15/02224) and it is part of the of the “CIBERCV”. Co-financed with FEDER Funds

Meta-análisis [Abstract] Introduction and objectives: To analyze survival in heart failure (HF) patients treated at a specialized unit. Methods: Prospective cohort-based study of HF patients treated at a specialized unit from 2011 to 2017. Observed 1- and 3-year mortality rates were compared with those predicted by the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. Results: We studied 1280 patients, whose median MAGGIC risk score was 19 [interquartile range, 13-24]. Prescription rates of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, and sacubitril-valsartan were 93%, 67%, 22%, 73%, and 16%, respectively. The MAGGIC risk score showed good discrimination for mortality at 1 year (c-statistic=0.71) and 3 years (c-statistic=0.76). Observed mortality was significantly lower than predicted mortality, both at 1 year (6.2% vs 10.9%; observed/predicted ratio=0.57; P 70 years (29.9% vs 34.7%; observed/predicted ratio=0.86; P=.126) and in patients with ejection fraction> 40% (19.6% vs 20.7%; observed/predicted ratio=0.95; P=.640). Conclusions: Mortality in HF patients treated at a specialized clinic was significantly lower than that predicted by the MAGGIC risk score. [Resumen] Introducción y objetivos. Analizar la supervivencia de los pacientes con insuficiencia cardiaca (IC) tratados en una unidad especializada. Métodos. Estudio prospectivo de una cohorte de pacientes con IC tratados en una unidad especializada entre 2011 y 2017. Se comparó la mortalidad observada a 1 y 3 años con la mortalidad pronosticada por la puntuación de riesgo del Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC). Resultados. Se estudió a 1.280 pacientes, con una mediana de la puntuación MAGGIC de 19 [intervalo intercuartílico, 13-24]. Las tasas de prescripción de bloqueadores beta, inhibidores de la enzima de conversión de la angiotensina, antagonistas del receptor de la angiotensina II, antagonistas del receptor de mineralcorticoides y sacubitrilo-valsartán fueron del 93, el 67, el 22, el 73 y el 16% respectivamente. La puntuación MAGGIC mostró una discriminación adecuada de la mortalidad a 1 año (estadístico c = 0,71) y a 3 años (estadístico c = 0,76). La mortalidad observada fue significativamente menor que la pronosticada, tanto a 1 año (el 6,2 frente al 10,9%; cociente observada/pronosticada = 0,57; p < 0,001) como a 3 años (el 16,7 frente al 27,7%; cociente observada/pronosticada = 0,60; p < 0,001). Esta discrepancia se observó en diversos subgrupos, excepto en los pacientes mayores de 70 años (el 29,9 frente al 34,7%; cociente observada/pronosticada = 0,86; p = 0,126) y en pacientes con fracción de eyección > 40% (el 19,6 frente al 20,7%; cociente observada/pronosticada = 0,95; p = 0,640). Conclusiones. Los pacientes con IC tratados en una unidad especializada presentaron una mortalidad inferior a la pronosticada por la puntuación MAGGIC.

To assess the risk factors of cytomegalovirus (CMV) infection after heart transplant (HT) and its influence on long-term prognosis.We conducted a retrospective single-centre study of 222 HT recipients. Risk factors for CMV infection were identified by means of multivariable Cox́s regression. Kaplan-Meier analysis and Cox́s regression were used to assess the long-term prognostic impact of CMV infection during the first post-transplant year.Donor-recipient CMV serologic matching (hazard ratio [HR] 1.92, 95% confidence interval [95% CI] 1.2-3.09, p=.007), recipient age (HR 1.02, 95% CI: 1.00-1.1, p=.02), diabetes mellitus (HR 1.86, 95% CI: 1.4-3.05, p=.01), pre-transplant circulatory support (HR 1.59, 95% CI: 1.06-2.38, p=.03) and the use of tacrolimus (HR 1.64, 95% CI: 1.13-2.36, p=.009) were independently associated with increased risk of CMV infection. CMV infection during the first year post-HT was not associated with worse transplant outcomes in terms of mortality, incidence of heart failure, cardiac allograft vasculopathy or acute rejection.CMV infection was not associated with impaired long-term prognosis after HT.

Purpose End-stage heart failure (HF) is often associated with malnutrition and sarcopenia, both of them are related to adverse HF outcomes. Skeletal muscle mass and attenuation are predictors of mortality after continuous flow left ventricular devices (LVAD) implantation. Our purpose was to assess the prognostic impact of skeletal muscle mass on patients undergoing heart transplantation (HT). Methods Retrospective study of a single-center HT population, between 2009 and 2019. Patients > 18 years-old with a computed chest scan in the previous 6 months before HT were included. Multiorgan transplants were excluded. Unilateral pectoralis muscle mass indexed (PMMi) to body surface area and attenuation (by mean Hounsfield units [PHUm]) were measured in each patient. HT patients were classifiedin tertiles according to PMMi and PHUm and characteristics of patients were compared by Chi-square, t-student and Kruskall-Wallis. Multivariate Cox regression analyses were performed to assess the impact of preoperative PMMi and PHUm on survival after HT. Results 132 patients were included, mean age 58.9, 16.7% female, median follow-up 3.67 years (interquartile range 1.7-5.9 years). 41.7% of patients underwent urgent HT (1.5% INTERMACS 1 situation, 15.2% INTERMACS 2 and 28% INTERMACS 3). Both PMMi and PHUm were lower in females and for lowest weight recipients. Urgent HT frequency was similar between tertiles of PMMi, but recipients in the higher tertile of PHUm were more frequently transplanted in an urgent status (38.2% vs 21.8% in the lowest tertile, p= 0.029). 26 patients (19.7%) died during follow-up, 12 (9.1% of total cohort) during HT admission. In the Cox regression analyses, neither PMMi (HR 1.034, 95% CI 0.891-1.2, p= 0.659) nor PHUm (HR 1.02, 95% CI 0.992-1.050, p=0.160) were associated with an increased mortality. Only the needed of mechanical circulatory support and hemofiltration after HT were associated with a higher risk of death. Conclusion Among this single-center HT recipients population, neither lower PMMi nor lower PHUm were associated with worse outcomes after HT.

Purpose Heart Transplant (HT) patients need complex drug treatment for life: many drugs and several daily doses (usually 5 times a day). This complexity may make it difficult to adhere to the treatment, which is key to therapeutic success. In order to facilitate medication preparation, a Weekly Multi-Dose Pillbox (WMDP-5), 5 doses/day, was designed in our HT program. The aim is to assess the improvement in adherence and satisfaction with the use of the WMDP-5 within a multifactorial intervention. Methods Prospective single-center study started in April 2019. All HT patients were invited to participate. The multilevel intervention included the provision of the WMDP-5 as well as a training session with a specific video and information leaflets. The study was approved by regional ethics committee. To evaluate adherence, the Spanish version of BAASIS (Basel Assessment of Adherence with Immunosuppressive Medication Scale) Patient Questionnaire Interview and the Simplified Medication Adherence Questionnaire (SMAQ) were used at delivery and at the follow-up visit. A Likert Scale (1-5) evaluate satisfaction at the follow-up visit (the next one to the center ≥ 1 months after using the WMDP). Patients with the follow-up visit until October 2019 were analyzed. Results A total of 214 HT patients (mean age 61,8±12,89 years, 79,4% males, with mean time after HT of 9,86±6,9 years) were included in the analysis. The highest level of education was primary school in 45,3%, 67,3% were married and 85% lived with someone. According to the SMAQ, there were 156/214 (72.89%) adherents at baseline and 193/214 (90,2%) at follow-up visit (p=0.006). Of 58 non-adherent patients at the baseline visit, 47 (81%) were adherent (improved) at the follow-up visit; while of 156 adherents at the basal visit, only 10 (6,4%) became non-adherents (worsened). The BAASIS questionnaire documented an overall improvement. Thus, the fist BAASIS question (if any pill was forgotten) at the baseline visit was 8%, while at the follow-up visit was 1,7%. Finally, according to the Likert Scale, 71,5% of the patients responded that the WMDP-5 helped them to take the treatment well. Conclusion The use of a WMDP-5 in the context of a multilevel intervention improves therapeutic adherence in HT patients. It should be noted that this improvement occurs in a cohort of HT patients with already high adherence.

Resumen Introduccion y objetivos Analizar el valor pronostico de la escala INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) en pacientes tratados con trasplante cardiaco urgente. Metodos Analisis retrospectivo de 111 pacientes tratados con trasplante cardiaco urgente en nuestro centro entre abril de 1991 y octubre de 2009. Se asigno retrospectivamente a los pacientes a tres niveles de la escala INTERMACS en funcion de su situacion clinica previa al trasplante cardiaco. Resultados Los pacientes del grupo INTERMACS 1 (n = 31) presentaban mayor frecuencia de cardiopatia isquemica (p = 0,03) y shock tras cardiotomia (p = 0,02) que los pacientes del grupo INTERMACS 2 (n = 55) y los pacientes del grupo INTERMACS 3–4 (n = 25), asi como mayores dosis de catecolaminas (p = 0,001), mayor empleo de ventilacion mecanica (p Conclusiones Nuestros resultados indican que la escala INTERMACS resulta util para estratificar el pronostico postoperatorio tras el trasplante cardiaco urgente.

[Abstract] We conducted an observational study of 30 heart transplant recipients with serum low-density lipoprotein cholesterol (LDL-c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long-term rosuvastatin therapy beyond this 12-week period were reviewed in February 2015. Over the 12-week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL-c and the ratio TC/high-density lipoprotein cholesterol (HDL-c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were –48.7 mg/dl, –46.6 mg/dl, and –0.9, respectively. Seventeen (57%) achieved a serum LDL-c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL-c, hepatic enzymes, bilirubin, or CPK. Twenty-seven (90%) patients continued on long-term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.

[Abstract] Background. A high frequency of venous thromboembolism (VTE) has been observed after lung, kidney, and liver transplantation. However, data about the incidence of this complication among heart transplant (HT) recipients are lacking. Methods. We analyzed the incidence, recurrence, and predisposing factors of VTE in a single-center cohort of 635 patients who underwent HT from April 1991 to April 2013. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE episodes. Results. During a median post-transplant follow-up of 8.4 years, 62 VTE episodes occurred in 54 patients (8.5%). Incidence rates of VTE, DVT, and PE were, respectively, 12.7 (95% confidence interval [CI], 9.7–16.3), 8.4 (95% CI, 6.0–11.4), and 7.0 (95% CI 4.8–9.7) episodes per 1,000 patient-years. Incidence rates of VTE during the first post-transplant year and beyond were, respectively, 45.1 (95% CI, 28.9–67.1) and 8.7 (95% CI 6.2–11.2) episodes per 1,000 patient-years. The incidence rate of VTE recurrence after a first VTE episode was 30.5 (95% CI, 13.2–60.2) episodes per 1,000 patient-years. By means of multivariable Cox regression, chronic renal dysfunction, older age, obesity, and the use of mammalian target of rapamycin inhibitors were identified as independent risk factors for VTE among HT recipients. Conclusions. VTE is a frequent complication after HT, mainly during the first post-operative year. In view of a high recurrence rate, long-term anti-coagulation should be considered in HT recipients who experience a first VTE episode.

[Abstract] Introduction and objectives. Our aim was to assess the prognostic value of the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) scale in patients undergoing urgent heart transplantation (HT). Methods. Retrospective analysis of 111 patients treated with urgent HT at our institution from April, 1991 to October, 2009. Patients were retrospectively assigned to three levels of the INTERMACS scale according to their clinical status before HT. Results. Patients at the INTERMACS 1 level (n = 31) more frequently had ischemic heart disease (p = 0.03) and post-cardiothomy shock (p = 0.02) than patients at the INTERMACS 2 (n = 55) and INTERMACS 3-4 (n = 25) levels. Patients at the INTERMACS 1 level showed higher preoperative catecolamin doses (p = 0.001), a higher frequency of use of mechanical ventilation (p < 0.001), intraaortic balloon (p = 0.002) and ventricular assist devices (p = 0.002), and a higher frequency of preoperative infection (p = 0.015). The INTERMACS 1 group also presented higher central venous pressure (p = 0.02), AST (p = 0.002), ALT (p = 0.006) and serum creatinine (p < 0.001), and lower hemoglobin (p = 0.008) and creatinine clearance (p = 0.001). After HT, patients at the INTERMACS 1 level had a higher incidence of primary graft failure (p = 0.03) and postoperative need for renal replacement therapy (p = 0.004), and their long-term survival was lower than patients at the INTERMACS 2 (log rank 5.1, p = 0.023; HR 3.1, IC 95% 1.1-8.8) and INTERMACS 3-4 level (log rank 6.1, p = 0.013; HR 6.8, IC 95% 1.2-39.1). Conclusions. Our results suggest that the INTERMACS scale may be a useful tool to stratify postoperative prognosis after urgent HT. [Resumen] Introducción y objetivos. Analizar el valor pronóstico de la escala INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) en pacientes tratados con trasplante cardiaco urgente. Métodos. Análisis retrospectivo de 111 pacientes tratados con trasplante cardiaco urgente en nuestro centro entre abril de 1991 y octubre de 2009. Se asignó retrospectivamente a los pacientes a tres niveles de la escala INTERMACS en función de su situación clínica previa al trasplante cardiaco. Resultados. Los pacientes del grupo INTERMACS 1 (n = 31) presentaban mayor frecuencia de cardiopatía isquémica (p = 0,03) y shock tras cardiotomía (p = 0,02) que los pacientes del grupo INTERMACS 2 (n = 55) y los pacientes del grupo INTERMACS 3-4 (n = 25), así como mayores dosis de catecolaminas (p = 0,001), mayor empleo de ventilación mecánica (p < 0,001), balón de contrapulsación (p = 0,002) y dispositivos de asistencia ventricular (p = 0,002) y mayores tasas de infección preoperatoria (p = 0,015). El grupo INTERMACS 1 también mostraba mayores cifras de presión venosa central (p = 0,02), GOT (p = 0,002), GPT (p = 0,006) y creatinina (p < 0,001) y menores cifras de hemoglobina (p = 0,008) y aclaramiento de creatinina (p = 0,001). Tras el trasplante cardiaco, los pacientes del grupo INTERMACS 1 presentaron mayores incidencias de fracaso primario del injerto (p = 0,03) y necesidad de terapia de sustitución renal (p = 0,004), y su supervivencia a largo plazo fue menor que la de los pacientes de los grupos INTERMACS 2 (log rank = 5,1; p = 0,023; razón de riesgos [HR] = 3,1; intervalo de confianza [IC] del 95%, 1,4-6,8) e INTERMACS 3-4 (log rank = 6,1; p = 0,013; HR = 4; IC del 95%, 1,3-12,3). Conclusiones. Nuestros resultados indican que la escala INTERMACS resulta útil para estratificar el pronóstico postoperatorio tras el trasplante cardiaco urgente.

Purpose Proliferation signal inhibitors(PSI) used after heart transplantation(HT) are useful in long-term complications. Proteinuria associated with use of PSI and possible deterioration of renal function may be related to use of calcineurin inhibitors (CNI). Purpose To determine the incidence of proteinuria after 1year of initiation everolimus (EVE) and analyze its relationship with CNI withdrawal and type of CNI. Methods and Materials Retrospective study of 54HT patients receiving EVE in late phase. 4patients were excluded due to basal pathological proteinuria and 7patients for CNI reintroduction. Immunosuppression was Cyclosporine (CyA) vs Tacrolimus (FK), MMF vs Azathioprine and prednisone. Proterinuria was determined using urine dipstick method and value Results 43HT patients analyzed(91% men, mean age 61±11 years), mean time between HT-EVE starting 5,5±4,8 years, CNI was discontinued in 10patients. Mean time of CNI withdrawal 24.7±17,4 days. Mean initial proteinuria(pre-EVE): 13’1 mg/dl(1,5-29,8). Incidence of proteinuria after EVE starting in patients with CNI/non-CNI at 3, 6 and 12 months was: 6(18%)/2(20%); 7(21%)/2(22%); 10(31%)/5(56%),p=NS; and with a median of 15,5(4-93)/25’5 (4-61); 15(7-53)/14(4-98); 19(7,7-93)/27(5-132), p=NS. Regarding to the CNI type (n=33; CyA12 and FK21), the incidence of proteinuria at 3,6 and 12 months in patients with CyA/FK was: 3(25%)/3(14%); 3(25%)/4(19%); 4(33%)/6(30%); and with a median of 19(8-33)/15(4-93); 14(9-52)/18(7-48); 22(8-92)/16(8-64), p=NS. Conclusions Incidence of proteinuria after 1year of EVE initiation in long-term HT is 34,8%. Combination of CNI with EVE does not increase significantly the development of proteinuria, although an increasing trend in the CNI withdrawal is observed. Comparison between CyA/FK also showed no significant differences. Further studies are needed to corroborate this hypothesis.

Purpose Proliferation signal inhibitors(PSI) used after heart transplantation(HT) may reduce post-HT complications. The proteinuria associated with using PSI leads to deterioration of renal function(RF). Purpose To determine the incidence of proteinuria after beginning of Everolimus(EVE) and his influence on RF. Methods and Materials Retrospective study of 54HT patients receiving EVE in late phase. 4patients were excluded due to basal pathological proteinuria. Immunosuppression was Cyclosporine (CyA) vs Tacrolimus (FK), MMF vs Azathioprine and prednisone. Proterinuria was determined using urine dipstick method and value Results 50HT patients were analyzed (92% men, mean age:61±11 years), mean time between HT-EVE initiation 6±5 years. The mean proteinurina and creatinine(pre-EVE) was 12’5 mg/dl(12- 7’6) and 1’56 mg/dl (0’8-3’30). 86% had statins and 48% ACEi or ARBs. After EVE starting the incidence of proteinuria at 1, 3, 6 and 12 months was: 5(10%), 9(18%), 10(20%), 14(28%) respectively, with a median of 11(1’5-29), 17’3(4-93), 14(3’9-98) and 18(5-132). Median of RF evolution analyzed according to proteinuria (absence/presence) at pre was 53’7/53’8 (21-103/29-160); and for months 1,3,6,12 was: 54’6/54’7 (25-105/28-154); 50’4/66’3 (20-107/25-154); 57/53 ( 23-109/25/100); 47’7/54’4 ( 28-94/29-118) respectively,p=NS. No significant differences were found in the development of proteinuria and taking ACEi or ARBs. Conclusions The incidence of proteinuria to the year of the EVE initiation in long-term HT patients is 28%. EVE utilization in patients without proteinuria before beginning appears safe and is not associated with a significant increase in proteinuria or renal impairment. However, the number is small so that further studies with larger series are needed to confirm this hypothesis.