Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry.

AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.

Evaluación del nivel de acceso a nuevas tecnologías y conocimiento del riesgo cardiovascular en pacientes cardiópatas hospitalizados / Evaluation of the level of access to new technologies and knowledge of cardiovascular risk in hospitalized patients with cardiac conditions

Objetivo: determinar el nivel de acceso a internet de los pacientes cardiópatas hospitalizados en el Área de Ferrol, Galicia (España) e indicar el grado de autoconocimiento del riesgo cardiovascular (RCV) en función del riesgo cardiovascular real calculado. Objetivos secundarios: evaluar los factores asociados a un mayor uso de recursos web y analizar los factores asociados a un mejor conocimiento del RCV.Métodos: estudio descriptivo transversal con pacientes ingresados en la unidad de cardiología en un mes (n= 106). Se recogieron variables sociodemográficas, de frecuencia de acceso a internet y de factores de RCV. Se calculó el RCV real y se comparó con el autopercibido. Se realizó un análisis descriptivo y se empleó el test Chi Cuadrado o test exacto de Fisher para analizar la asociación entre diferentes variables con el nivel de acceso a internet.Resultados: de los 89 pacientes incluidos, la edad media era de 64,6 (DE:12,3) años, el 76,4% era hombre, con formación básica (58,4%) y casado (75,3%). El 40,6% manifestó no acceder nunca a internet, el 18% hacerlo de forma ocasional, el 11,2% de forma frecuente y el 30,3% hacerlo diariamente. El uso de recursos web fue significativamente mayor en pacientes con mayor formación y más jóvenes. Únicamente el 19,1% estimó de forma correcta su RCV y no se halló ningún factor asociado a un mejor conocimiento del RCV.Conclusión: la Educación para la Salud es necesaria y debe mejorarse; sin embargo, el uso de recursos web no puede considerarse la única herramienta en esta área sanitaria en la actualidad.(AU)

Objective: to determine the level of access to internet among patients with cardiac conditions hospitalized at the Ferrol Area, Galicia (Spain), and to state their level of self-knowledge of cardiovascular risk (CVR) based on their estimated real cardiovascular risk. Secondary endpoints: To assess those factors related to a higher use of web resources, and to analyze those factors associated with a better knowledge of their CVR.Methods: a cross-sectional descriptive study with patients admitted to the Cardiology Unit in one month (n= 106). Sociodemographic variables were collected, as well as frequency of internet access and CVR factors. The real CVR was calculated, and compared with their self-perceived risk. Descriptive analysis was conducted, and the Chi Square test or Fisher’s Exact Test was used to analyze the association between different variables and their level of access to internet.Results: the age of the 89 patients included was 64.6 (SD:12.3) years, 76.4% were male, with basic education (58.4%) and married (75.3%). Out of these, 40.6% stated that they never accessed internet, 18% did it occasionally, 11.2% frequently, and 30.3% did it every day. The use of web resources was significantly higher in younger patients and those with higher education. Only 19.1% calculated their CVR correctly, and no factor was found to determine a higher knowledge of CVR.Conclusion: health Education is necessary and must be improved; however, the use of web resources cannot be considered currently the only tool in this health area.(AU)

Economic evaluation of complete revascularization versus stress echocardiography-guided revascularization in the STEACS with multivessel disease.

INTRODUCTION AND OBJECTIVES: Economic studies may help decision making in the management of multivessel disease in the setting of myocardial infarction. We sought to perform an economic evaluation of CROSS-AMI (Complete Revascularization or Stress Echocardiography in Patients With Multivessel Disease and ST-Segment Elevation Acute Myocardial Infarction) randomized clinical trial. METHODS: We performed a cost minimization analysis for the strategies (complete angiographic revascularization [ComR] and selective stress echocardiography-guided revascularization [SelR]) compared in the CROSS-AMI clinical trial (N=306), attributable the initial hospitalization and readmissions during the first year of follow-up, using current rates for health services provided by our health system. RESULTS: The index hospitalization costs were higher in the ComR group than in SelR arm (19 657.9±6236.8 € vs 14 038.7±4958.5 €; P <.001). There were no differences in the costs of the first year of follow-up rehospitalizations between both groups for (ComR 2423.5±4568.0 vs SelR 2653.9±5709.1; P=.697). Total cost was 22 081.3±7505.6 for the ComR arm and 16 692.6±7669.9 for the SelR group (P <.001). CONCLUSIONS: In the CROSS-AMI trial, the initial extra economic costs of the ComR versus SelR were not offset by significant savings during follow-up. SelR seems to be more efficient than ComR in patients with ST-segment elevation acute coronary syndrome and multivessel disease treated by emergent angioplasty. Study registred at ClinicalTrial.gov (Identifier: NCT01179126).

Comparación de mortalidad pronosticada y mortalidad observada en pacientes con insuficiencia cardiaca tratados en una unidad clínica especializada / Comparison of predicted and observed mortality in patients with heart failure treated at a specialized unit

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

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<.001) and at 3 years (16.7% vs 27.7%; observed/predicted ratio=0.60; P<.001). This discrepancy was found in several subgroups, except in patients aged> 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

Comparison of predicted and observed mortality in patients with heart failure treated at a specialized unit.

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<.001) and at 3 years (16.7% vs 27.7%; observed/predicted ratio=0.60; P<.001). This discrepancy was found in several subgroups, except in patients aged> 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.

Pulmonary Arteriovenous Malformation and Embolic Myocardial Infarction in a Patient With Hereditary Hemorrhagic Telangiectasia.

This report describes a case of embolic myocardial infarction secondary to a pulmonary arteriovenous malformation. Pulmonary arteriovenous malformations are rare and mostly congenital and are inherited as an autosomal dominant disorder known as hereditary hemorrhagic telangiectasia. Myocardial infarction is an uncommon complication in patients with untreated pulmonary arteriovenous malformations. (Level of Difficulty: Advanced.).

Valor pronóstico del índice de riesgo nutricional en receptores de trasplante cardiaco / Prognostic value of the nutritional risk index in heart transplant recipients

Introducción y objetivos: Analizar el impacto del estado nutricional preoperatorio, evaluado mediante el índice de riesgo nutricional (IRN), en el pronóstico tras el trasplante cardiaco (TxC). Métodos: Se realizó un estudio retrospectivo de 574 pacientes que recibieron un TxC entre 1991 y 2014 en un centro. El IRN preoperatorio se calculó como 1,519 × albúmina (g/l) + 41,7 × (peso real [kg] / peso ideal [kg]). La asociación entre IRN preoperatorio y eventos clínicos posoperatorios se analizó mediante modelos multivariables de regresión logística y regresión de Cox. Resultados: El IRN preoperatorio medio de la población del estudio era de 100,9 ± 9,9. Según este parámetro, las prevalencias de riesgo nutricional grave (IRN < 83,5), moderado (83,5 ≤ IRN < 97,5) y leve (97,5 ≤ IRN < 100) antes del TxC eran el 5, el 22 y el 10% respectivamente. Las tasas de mortalidad a 1 año tras el TxC en estas 4 categorías fueron del 18,2, el 25,3, el 7,9 y el 10,2% (p < 0,001) respectivamente. El IRN preoperatorio resultó predictor independiente de menor riesgo de infección posoperatoria (odds ratio ajustada [ORa] = 0,97; intervalo de confianza del 95% [IC95%], 0,95-1,00; p = 0,027) y ventilación mecánica prolongada posoperatoria (ORa = 0,96; IC95%, 0,94-0,98; p = 0,001). Los pacientes con riesgo nutricional moderado a grave mostraron mayor mortalidad a 1 año tras el TxC (hazard ratio ajustada = 1,55; IC95%, 1,22-1,97; p < 0,001). Conclusiones: Los pacientes desnutridos tienen mayor riesgo de complicaciones posoperatorias y muerte tras el TxC. La determinación del IRN podría facilitar la identificación de candidatos a TxC que se beneficien de intervenciones nutricionales en espera del órgano (AU)

Introduction and objectives: To study the prognostic impact of preoperative nutritional status, as assessed through the nutritional risk index (NRI), on postoperative outcomes after heart transplantation (HT). Methods: We conducted a retrospective, single-center study of 574 patients who underwent HT from 1991 to 2014. Preoperative NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (body weight [kg] / ideal body weight [kg]). The association between preoperative NRI and postoperative outcomes was analyzed by means of multivariable logistic regression and multivariable Cox regression. Results: Mean NRI before HT was 100.9 ± 9.9. According to this parameter, the prevalence of severe nutritional risk (NRI < 83.5), moderate nutritional risk (83.5 ≤ NRI < 97.5), and mild nutritional risk (97.5 ≤ NRI < 100) was 5%, 22%, and 10%, respectively. One year post-transplant mortality rates in these 4 categories were 18.2%, 25.3%, 7.9% and 10.2% (P < .001), respectively. The NRI was independently associated with a lower risk of postoperative infection (adjusted OR, 0.97; 95%CI, 0.95-1.00; P = .027) and prolonged postoperative ventilator support (adjusted OR, 0.96; 95%CI, 0.94-0.98; P = .001). Patients at moderate or severe nutritional risk had significantly higher 1-year post-HT mortality (adjusted HR, 1.55; 95%CI, 1.22-1.97; P < .001). Conclusions: Malnourished patients have a higher risk of postoperative complications and mortality after HT. Preoperative NRI determination may help to identify HT candidates who might benefit from nutritional intervention (AU)

Prognostic Value of the Nutritional Risk Index in Heart Transplant Recipients.

INTRODUCTION AND OBJECTIVES: To study the prognostic impact of preoperative nutritional status, as assessed through the nutritional risk index (NRI), on postoperative outcomes after heart transplantation (HT). METHODS: We conducted a retrospective, single-center study of 574 patients who underwent HT from 1991 to 2014. Preoperative NRI was calculated as 1.519 × serum albumin (g/L) + 41.7 × (body weight [kg] / ideal body weight [kg]). The association between preoperative NRI and postoperative outcomes was analyzed by means of multivariable logistic regression and multivariable Cox regression. RESULTS: Mean NRI before HT was 100.9 ± 9.9. According to this parameter, the prevalence of severe nutritional risk (NRI < 83.5), moderate nutritional risk (83.5 ≤ NRI < 97.5), and mild nutritional risk (97.5 ≤ NRI < 100) was 5%, 22%, and 10%, respectively. One year post-transplant mortality rates in these 4 categories were 18.2%, 25.3%, 7.9% and 10.2% (P < .001), respectively. The NRI was independently associated with a lower risk of postoperative infection (adjusted OR, 0.97; 95%CI, 0.95-1.00; P = .027) and prolonged postoperative ventilator support (adjusted OR, 0.96; 95%CI, 0.94-0.98; P = .001). Patients at moderate or severe nutritional risk had significantly higher 1-year post-HT mortality (adjusted HR, 1.55; 95%CI, 1.22-1.97; P < .001). CONCLUSIONS: Malnourished patients have a higher risk of postoperative complications and mortality after HT. Preoperative NRI determination may help to identify HT candidates who might benefit from nutritional intervention.

Estado serológico frente a Toxoplasma gondii en receptores de trasplante cardiaco: ¿un factor pronóstico independiente? / Toxoplasma gondii serostatus in heart transplant recipients: is it an independent prognostic factor?

Introducción y objetivos: Analizar la influencia pronóstica del estado serológico frente a Toxoplasma gondii en receptores de trasplante cardiaco (TC). Métodos: Se realizó un estudio retrospectivo unicéntrico con 657 receptores de TC entre 1991 y 2015. Mediante dos modelos multivariantes de Cox se comparó la supervivencia y la incidencia de episodios clínicos adversos de los receptores seropositivos (n = 481) y los receptores seronegativos (n = 176) frente a T. gondii. El modelo 1 incluyó edad y sexo, y el modelo 2 incluyó otros factores de confusión potenciales. Resultados: Con una mediana de seguimiento de 2.903 días (rango intercuartílico: 898-4.757), fallecieron 250 pacientes seropositivos (52%) y 72 receptores seronegativos (41%) frente a T. gondii. Los pacientes seropositivos presentaron mayor mortalidad no ajustada tras el TC (hazard ratio[HR] = 1,31; intervalo de confianza del 95% [IC95%], 1,00-1,70). Tras el ajuste multivariante, este efecto perdió su significación estadística (modelo 1: HR = 1,09; IC95%, 0,83-1,43; modelo 2: HR = 1,12; IC95%, 0,85-1,47). La seropositividad frente a T. gondii del receptor se asoció de modo independiente con mayor riesgo de rechazo agudo (modelo 1: HR = 1,36; IC95%, 1,06-1,74; modelo 2: HR = 1,29; IC95%, 1,01-1,66). Los modelos multivariantes no pusieron de manifiesto una influencia significativa del estado serológico frente a T. gondii del receptor sobre la incidencia de infección, neoplasias, enfermedad vascular del injerto o el desenlace combinado muerte cardiaca o retrasplante. Tampoco se observó una influencia pronóstica significativa de la concordancia donante-receptor respecto al estado serológico frente a T. gondii. Conclusiones: El presente estudio no ha puesto de manifiesto un efecto pronóstico independiente del estado serológico frente a T. gondii en los receptores de TC (AU)

Introduction and objectives: To assess the potential association between recipient Toxoplasma gondii serostatus and outcomes after heart transplant (HT). Methods: We conducted a retrospective single-center study of 657 HT recipients from 1991 to 2015. Survival and the incidence of adverse clinical events of T. gondii-seropositive (n = 481) vs T. gondii-seronegative (n = 176) recipients were compared by means of 2 different multivariable Cox regression models. Model 1 included solely age and sex, and model 2 included other potential confounders. Results: Over a median follow-up of 2903 days (interquartile range: 898-4757), 250 seropositive recipients (52%) and 72 seronegative recipients (41%) died. Univariable analysis showed increased posttransplant mortality among T. gondii-seropositive recipients (hazard ratio [HR] = 1.31; 95% confidence interval [95%CI], 1,00-1.70). After multivariable adjustment, the statistical significance of this association was lost (model 1: HR = 1.09; 95%CI, 0.83-1.43; model 2:HR = 1.12; 95%CI, 0.85-1.47). Recipient T. gondii seropositivity was independently associated with an increased risk of acute rejection (model 1: HR = 1.36; 95%CI, 1.06-1.74; model 2: HR = 1.29; 95%CI, 1.01-1.66). Multivariable models showed no statistically significant impact of recipient T. gondii serostatus on the incidence of infection, malignancy, coronary allograft vasculopathy, or the composite outcome of cardiac death or retransplant. No significant association was found between donor-recipient T. gondii serostatus matching and posttransplant outcome. Conclusions: In this study, recipient T. gondii serostatus was not an independent predictor of long-term post-HT outcome (AU)

Toxoplasma Gondii Serostatus in Heart Transplant Recipients: Is It an Independent Prognostic Factor?

INTRODUCTION AND OBJECTIVES: To assess the potential association between recipient Toxoplasma gondii serostatus and outcomes after heart transplant (HT). METHODS: We conducted a retrospective single-center study of 657 HT recipients from 1991 to 2015. Survival and the incidence of adverse clinical events of T. gondii-seropositive (n = 481) vs T. gondii-seronegative (n = 176) recipients were compared by means of 2 different multivariable Cox regression models. Model 1 included solely age and sex, and model 2 included other potential confounders. RESULTS: Over a median follow-up of 2903 days (interquartile range: 898-4757), 250 seropositive recipients (52%) and 72 seronegative recipients (41%) died. Univariable analysis showed increased posttransplant mortality among T. gondii-seropositive recipients (hazard ratio [HR] = 1.31; 95% confidence interval [95%CI], 1,00-1.70). After multivariable adjustment, the statistical significance of this association was lost (model 1: HR = 1.09; 95%CI, 0.83-1.43; model 2:HR = 1.12; 95%CI, 0.85-1.47). Recipient T. gondii seropositivity was independently associated with an increased risk of acute rejection (model 1: HR = 1.36; 95%CI, 1.06-1.74; model 2: HR = 1.29; 95%CI, 1.01-1.66). Multivariable models showed no statistically significant impact of recipient T. gondii serostatus on the incidence of infection, malignancy, coronary allograft vasculopathy, or the composite outcome of cardiac death or retransplant. No significant association was found between donor-recipient T. gondii serostatus matching and posttransplant outcome. CONCLUSIONS: In this study, recipient T. gondii serostatus was not an independent predictor of long-term post-HT outcome.

Analysis of variants in the HCN4 gene and in three single nucleotide polymorphisms of the CYP3A4 gene for association with ivabradine reduction in heart rate: A preliminary report.

BACKGROUND: Ivabradine, a selective bradycardic drug, inhibits the If. In patients with heart failure (HF), ivabradine reduces the risk of rehospitalization and mortality. The average heart rate (HR) reduction is 8-10 beats, although clinical trials reveal interindividual variability. The aim of the study is to identify variants associated with HR reduction produced by ivabradine in genes involved in the drug metabolism (CYP3A4) or related to the drug target (HCN4). METHODS: In an exploratory cohort (n = 11), patients started on ivabradine were genotyped and the HR reduction was studied. RESULTS: The mean HR reduction after the treatment was 18.10 ± 12.26 bpm. The HR reduction was ≥ 15 bpm in 3 patients and > 5 and < 15 bpm in 7 patients. Four synonymous variants, L12L, L520L, P852P, and P1200P, were detected in the HCN4 gene (frequency = 0.045, 0.045, and 0.681, respectively). Moreover, the CYP3A4*1F and CYP3A4*1B were found in one patient each and CYP3A4*1G was presented in 3 patients. CONCLUSIONS: This is the first study using an exploratory pharmacogenetic approach that attempts to explain interindividual variability in ivabradine HR reduction. However, more research must be undertaken in order to determine the role of variants in HCN4 and CYP3A4 genes in response to ivabradine.

Significado pronóstico y evolución a largo plazo de la frecuencia cardiaca en los pacientes con trasplante cardiaco / Prognostic significance of heart rate and its long-term trend in cardiac transplant patients

Introducción y objetivos. Estudiar la evolución y el significado pronóstico de la frecuencia cardiaca tras el trasplante cardiaco. Métodos. Estudio observacional de 170 pacientes que recibieron un trasplante cardiaco bicavo entre 1995 y 2005; todos estaban en ritmo sinusal. La frecuencia cardiaca en reposo se determinó a partir de electrocardiogramas al final del primer año tras el trasplante y anualmente hasta el décimo año. Mediante análisis de Cox, se evaluó la incidencia de eventos adversos en un seguimiento medio de 8,9 ± 3,1 años. El evento principal del estudio fue la variable combinada muerte o disfunción del injerto. Resultados. La frecuencia cardiaca en reposo, medida al final del primer año tras el trasplante, fue un predictor independiente del evento combinado principal (hazard ratio = 1,054; intervalo de confianza del 95%, 1,028-1,080; p < 0,001). Se observó una asociación estadísticamente significativa con la mortalidad total (hazard ratio = 1,058; intervalo de confianza del 95%, 1,030-1,087; p < 0,001) y con la mortalidad por causas cardiacas (hazard ratio = 1,069; intervalo de confianza del 95%, 1,026-1,113; p = 0,001), pero no con la disfunción del injerto (hazard ratio = 1,028; intervalo de confianza del 95%, 0,989-1,069; p = 0,161). Para los pacientes con frecuencia cardiaca ≥ 105 y < 90 lpm frente a aquellos con 90-104 lpm, las hazard ratio del evento principal fueron, respectivamente, 2,233 (intervalo de confianza del 95%, 1,250-3,989, p = 0,007) y 0,380 (intervalo de confianza del 95%, 0,161-0,895; p = 0,027). Este parámetro presentó una tendencia decreciente en los primeros 10 años del trasplante (p = 0,001). Los pacientes con incremento neto de frecuencia cardiaca en el seguimiento mostraron mayor incidencia de eventos adversos. Conclusiones. La frecuencia cardiaca elevada es un marcador pronóstico adverso tras el trasplante cardiaco (AU)

Introduction and objectives. The aim of the present study was to examine the prognostic significance of heart rate and its trend in heart transplantation. Methods. This observational study enrolled 170 patients who received a bicaval heart transplant between 1995 and 2005; all were in sinus rhythm. The resting heart rate was determined via electrocardiography at the end of the first posttransplant year and annually until the tenth year. Cox analysis was used to evaluate the incidence of adverse events with a mean (standard deviation) follow-up of 8.9 (3.1) years. The primary study end point was the composite outcome of death or graft dysfunction. Results. The resting heart rate at the end of the first posttransplant year was an independent predictor of the primary composite end point (hazard ratio = 1.054; 95% confidence interval, 1.028-1.080; P < .001) and was significantly associated with total mortality (hazard ratio = 1.058; 95% confidence interval, 1.030-1.087; P < .001) and mortality from cardiac causes (hazard ratio = 1.069; 95% confidence interval, 1.026-1.113; P = .001), but not with graft dysfunction (hazard ratio = 1.028; 95% confidence interval, 0.989-1.069; P = .161). For patients with a heart rate ≥ 105 or < 90 bpm vs those with 90-104 bpm, the hazard ratios of the primary end point were 2.233 (95% confidence interval, 1.250-3.989; P = .007) and 0.380 (95% confidence interval, 0.161-0.895; P = .027), respectively. Heart rate tended to decrease in the first 10 years after transplantation (P = .001). Patients with a net increase in heart rate during follow-up showed a higher incidence of adverse events. Conclusions. An elevated heart rate is an adverse prognostic marker after heart transplantation (AU)

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.

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.

Prognostic Significance of Heart Rate and its Long-term Trend in Cardiac Transplant Patients.

INTRODUCTION AND OBJECTIVES: The aim of the present study was to examine the prognostic significance of heart rate and its trend in heart transplantation. METHODS: This observational study enrolled 170 patients who received a bicaval heart transplant between 1995 and 2005; all were in sinus rhythm. The resting heart rate was determined via electrocardiography at the end of the first posttransplant year and annually until the tenth year. Cox analysis was used to evaluate the incidence of adverse events with a mean (standard deviation) follow-up of 8.9 (3.1) years. The primary study end point was the composite outcome of death or graft dysfunction. RESULTS: The resting heart rate at the end of the first posttransplant year was an independent predictor of the primary composite end point (hazard ratio=1.054; 95% confidence interval, 1.028-1.080; P<.001) and was significantly associated with total mortality (hazard ratio=1.058; 95% confidence interval, 1.030-1.087; P<.001) and mortality from cardiac causes (hazard ratio=1.069; 95% confidence interval, 1.026-1.113; P=.001), but not with graft dysfunction (hazard ratio=1.028; 95% confidence interval, 0.989-1.069; P=.161). For patients with a heart rate ≥ 105 or<90 bpm vs those with 90-104 bpm, the hazard ratios of the primary end point were 2.233 (95% confidence interval, 1.250-3.989; P=.007) and 0.380 (95% confidence interval, 0.161-0.895; P=.027), respectively. Heart rate tended to decrease in the first 10 years after transplantation (P=.001). Patients with a net increase in heart rate during follow-up showed a higher incidence of adverse events. CONCLUSIONS: An elevated heart rate is an adverse prognostic marker after heart transplantation.

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

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.

Prevention and treatment of coronary artery vasculopathy.

PURPOSE OF REVIEW: Cardiac allograft vasculopathy (CAV) is still one of the major causes of death following heart transplantation. Here, we review the recent advances in its prevention and treatment. RECENT FINDINGS: Preventive measures comprise control of classical risk factors, prophylaxis against cytomegalovirus, avoidance of graft endothelial damage during heart transplantation, and prevention of acute rejection. These measures can be effective if begun early. The treatment options for established CAV are limited, percutaneous revascularization and coronary artery bypass graft only being viable for a minority of patients because of the diffuse nature of CAV. Retransplantation is the only definitive therapy for CAV and may be considered for suitable patients with advanced CAV and allograft dysfunction. One of the most promising developments in the recent years is the use of mTOR inhibitors, which can now be regarded as effective in preventing CAV in de novo patients; their role in the treatment of established CAV is still uncertain despite some encouraging recent findings. SUMMARY: The implementation of measures and lifestyles that help prevent CAV should be a priority of postheart transplantation management. Research should urgently evaluate mTOR inhibitors for the treatment of established CAV.