Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short-term and long-term efficacy and safety results

[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

Incidencia, factores de riesgo e impacto pronóstico de la infección por citomegalovirus tras el trasplante cardiaco

[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

Comparación de mortalidad pronosticada y mortalidad observada en pacientes con insuficiencia cardiaca tratados en una unidad clínica especializada

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 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

Determinants of Maximal Oxygen Uptake in Patients With Heart Failure

[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

Venous thromboembolism in heart transplant recipients: Incidence, recurrence and predisposing factors

[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

Usefulness of the INTERMACS scale for predicting outcomes after urgent heart transplantation

[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

Galectina-3 circulante tras el trasplante cardiaco: dinámica a largo plazo y valor pronóstico

[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<.001). Circulating Gal-3 levels 1-year posttransplant were associated with an increased risk of all-cause death or graft failure (adjusted HR per 1 ng/mL, 1.04; 95%CI, 1.01-1.08; P=.008). The predictive accuracy of this biomarker was moderate: area under the ROC curve, 0.72 (95%CI, 0.60-0.82; P<.001). Conclusions: Circulating Gal-3 steadily decreased during the first year after HT. However, 1-year posttransplant Gal-3 serum levels that remained elevated were associated with increased long-term risk of death and graft failure.[Resumen] Introducción y objetivos. Los valores plasmáticos de galectina-3 (Gal-3) están elevados y se correlacionan con la mortalidad total y cardiovascular en pacientes con insuficiencia cardiaca, pero su correlación con el pronóstico tras el trasplante cardiaco (TxC) es desconocida. El objetivo fue describir la tendencia evolutiva y el valor pronóstico de este biomarcador tras el TxC. Métodos. Mediante enzimoinmunoensayo, se midieron las concentraciones plasmáticas de Gal-3 en muestras de suero de 122 receptores de TxC, antes y 1, 3, 6 y 12 meses después de este. Mediante regresión de Cox se analizó el valor pronóstico del valor plasmático de Gal-3 a los 12 meses del TxC. El objetivo primario del estudio fue la variable combinada muerte o disfunción del injerto. Resultados. Las concentraciones de Gal-3 disminuyeron progresivamente durante el primer año tras el TxC (medianas: pretrasplante, 19,1 ng/ml; 1 año postrasplante, 14,6 ng/ml; p < 0,001). Los valores de Gal-3 1 año tras el TxC se asociaron con mayor riesgo de muerte o disfunción del injerto (HR por 1 ng/ml: 1.04; IC95%: 1,01-1,08; p = 0,008). La capacidad predictiva del biomarcardor fue moderada: área bajo la curva ROC, 0,72 (IC95%: 0,60-0,82; p < 0,001). Conclusiones. Las concentraciones plasmáticas de Gal-3 disminuyeron progresivamente durante el primer año tras el TxC. Un valor plasmático elevado de Gal-3 1 año tras el TxC se correlacionó con un pronóstico adverso.Instituto de Salud Carlos III; PI12/0267

Determinants and prognostic value of peak oxygen uptake in the current era of heart failure disease modifying therapy

Abstrac

Caso clínico. Gestión ineficaz de la propia salud: Dificultades en el aprendizaje en paciente con trasplante cardiaco

Heart transplantation is the therapeutic choice for heart failure in terminal stage. We report the case of a 69-year-old male with dilated cardiomyopathy, one of the main indications for heart transplantation. He undergoes transplantation with the need for circulatory support measures, in an emergency context 1. Once the multidisciplinary team verified that the patient possesses the necessary skills and knowledge, he is discharged 11 days after transplantation. To emphasize the importance that correctly adhering to therapeutic indications and maintaining compliance with them have on transplantation success (patient/graft). In accordance with the Virginia Henderson›s needs model and the NANDA-NIC-NOC taxonomy, collaboration issues and the main nursing diagnoses are described. The goal is to favor learning and skill development by patient and family in the management of heart transplantation in their daily life.El trasplante cardiaco es la alternativa terapéutica para la insuficiencia cardiaca en fase terminal. Se presenta el caso clínico de un varón de 69 años con miocardiopatía dilatada, una de las principales indicaciones de trasplante cardiaco. Es trasplantado precisando medidas de soporte circulatorio, en contexto de urgencia 1. Una vez que el equipo multidisciplinar se aseguró de que el paciente posee las capacidades y conocimientos necesarios es dado de alta 11 días después del trasplante. Destacar la importancia que tiene para el éxito del trasplante (paciente/injerto) seguir correctamente las indicaciones terapéuticas y mantener su cumplimiento. Siguiendo el modelo de necesidades de Virginia Henderson y taxonomía NANDA-NIC-NOC se describen los problemas de colaboración y los principales diagnósticos de enfermería. El objetivo es favorecer el aprendizaje y desarrollo de habilidades por parte de paciente y familia en el manejo del trasplante cardiaco en su vida diaria