Hypoalbuminemia in acute heart failure patients: causes and its impact on hospital and long-term mortality.

BACKGROUND: The causes of hypoalbuminemia in patients with acute heart failure (HF) remain poorly defined, and the association between hypoalbuminemia and hospital and long-term mortality has been only partially evaluated. This study sought to analyze the causes of hypoalbuminemia in acute HF patients and determine its impact on hospital and long-term mortality. METHODS AND RESULTS: A total of 362 consecutive acute HF patients were assessed. The patients were divided into 2 groups according to the presence or absence of hypoalbuminemia (albumin ≤3.4 g/dL), and the independent association of each variable with hypoalbuminemia and hospital mortality was assessed with the use of multiple logistic regression. The association between hypoalbuminemia and long-term mortality was assessed with the use of Cox multivariate analysis. In total, 108 patients (29.8%) were classified as having hypoalbuminemia. Older age, higher C-reactive protein levels, and lower levels of total protein, prealbumin, transferrin, and lymphocytes were independently associated with hypoalbuminemia. Hospital mortality was 8% and was independently associated with hypoalbuminemia. A total of 333 patients were discharged. Hypoalbuminemia was an independent predictor of mortality. CONCLUSIONS: Hypoalbuminemia in acute HF patients was associated with higher hospital mortality and served as an independent predictor of long-term mortality. Malnutrition and inflammation were factors causing hypoalbuminemia in this clinical setting.

[Effect of omega-3 fatty acids on hypoalbuminemia in acute heart failure patients with increased inflammatory activity]. / Efecto de los ácidos grasos omega-3 sobre la hipoalbuminemia en pacientes con insuficiencia cardiaca aguda y actividad inflamatoria elevada.

INTRODUCTION: Introduction: inflammatory activity (IA) is a cause of hypoalbuminemia in patients with acute heart failure (AHF). Objectives: the main objective of this study was to evaluate whether an AI modulator treatment contributes to correcting albuminemia in this context. Methods: in this clinical trial 43 patients with AHF, hypoalbuminemia (serum albumin  3.4 g/dl), and elevated IA [C-reactive protein (CRP)  25 mg/l] were randomly assigned to receive omega-3 fatty acids (4 g daily) or placebo for 4 weeks. Albuminemia and CRP were reassessed at weeks 1 and 4. An analysis of variance for repeated measures was performed. Results: mean age was 75.6 ± 8.8 years, 72.1 % were male, and the most frequent etiology was ischemic (46.5 %). The two groups were homogeneous in their baseline characteristics. A significant increase in albumin concentration was found at week 4 from baseline (p for the effect of time < 0.001), with no differences between groups at week 1 or week 4. CRP decreased significantly in week 1 (p for the effect of time < 0.001), with no differences between groups in either week 1 or week 4. Conclusion: in patients with AHF, hypoalbuminemia, and elevated AI albuminemia normalizes in week 4, while CRP already drops significantly during the first week. In this context both effects are independent of the addition of high doses of omega-3 fatty acids.

INTRODUCCIÓN: Introducción: la actividad inflamatoria (AI) es causa de hipoalbuminemia en los pacientes con insuficiencia cardiaca aguda (ICA). Objetivos: el objetivo principal de este estudio fue evaluar si un tratamiento modulador de la AI contribuye a corregir la albuminemia en este contexto. Métodos: en este ensayo clínico, 43 pacientes con ICA, hipoalbuminemia (albúmina sérica ≤ 3,4 g/dl) y AI elevada [proteína C-reactiva (PCR)  25 mg/l] fueron asignados aleatoriamente a recibir ácidos grasos omega-3 (4 g diarios) o placebo durante 4 semanas. La albuminemia y la PCR se reevaluaron en las semanas 1 y 4. Se realizó un análisis de la varianza para medidas repetidas. Resultados: la edad media era de 75,6 ± 8,8 años, el 72,1 % eran varones y la etiología más frecuente era la isquémica (46,5 %). Los dos grupos fueron homogéneos en sus características basales. Se encontró un incremento significativo de la concentración de albúmina en la semana 4 con respecto a la basal (p del efecto tiempo < 0,001), sin que se hallaran diferencias entre los grupos ni en la semana 1 ni en la 4. La PCR descendió significativamente ya en la semana 1 (p del efecto tiempo < 0,001), sin que se encontraran diferencias entre los grupos ni en la semana 1 ni en la 4. Conclusión: en los pacientes con ICA, hipoalbuminemia y AI elevada, la albuminemia se normaliza en la semana 4 mientras que la PCR desciende significativamente en la primera semana. En este contexto, ambos efectos son independientes de la adición de altas dosis de ácidos grasos omega-3.

Nutritional intervention in acute heart failure patients with undernutrition and normalbuminemia: A subgroup analysis of PICNIC study.

BACKGROUND & AIMS: Hypoalbuminemia is common in acute heart failure (HF) patients and has been associated with increased hospital mortality and long-term mortality. Undernutrition is a factor causing hypoalbuminemia. The PICNIC study results show that a nutritional intervention in undernourished acute HF patients reduces the risks of all-cause death and of readmission for HF. We aimed to investigate whether the efficacy of a nutritional intervention is consistent among the subgroups of patients with and without hypoalbuminemia. METHODS: In PICNIC study, a total of 120 malnourished hospitalized patients due to acute HF were randomized to conventional HF treatment or conventional HF treatment combined with an individualized nutritional intervention. The primary endpoint was a composite of all-cause death or readmission for worsening of HF, with a maximum follow-up of 12 months. In this post-hoc sub-analysis we assessed the interaction of the effects of a nutritional intervention among patients with and without hypoalbuminemia. Analysis was by intention to treat. RESULTS: 59 (49,2%) patients demonstrated hypoalbuminemia and 61 (50,8%) had normalbuminemia. At 12 months, the number of events for the primary endpoint in the intervention group compared with the control group was consistent among patients with hypoalbuminemia (28.6% intervention vs 61.3% control, HR 0,35, 95% CI 0,15-0,81) and those without (25.8% intervention vs 60% control, HR 0,35, 95% CI 0,15-0,79; interaction p = 0,86). CONCLUSION: There was no evidence that the relative efficacy of a nutritional intervention in undernourished acute HF patients was different between patients with normalbuminemia and those with hypoalbuminemia.

Has the clinical profile of patients with nonvalvular atrial fibrillation treated with rivaroxaban changed in the last 5 years of use?

AIM: To analyze the evolution of clinical profile of patients with nonvalvular atrial fibrillation treated with rivaroxaban. METHODS: Retrospective study in which patients treated with rivaroxaban were divided into two groups according to the data in which the initial prescription was performed (November 2012-December 2013 and January 2014-January 2017). RESULTS: 211 patients (mean age 76.7 ± 9.2 years; CHA2DS2-VASc 3.8 ± 1.5; HAS-BLED 2.0 ± 0.8.) were included. Age and bleeding risk were higher in those subjects in which the prescription started earlier. Rates of stroke/TIA, major bleeding and intracranial hemorrhage were 2.3/4.2/0.6 events/100 patient-years, respectively. CONCLUSION: Although, the initial prescription of rivaroxaban was mainly performed in very elderly patients and/or with a higher bleeding risk, this has been extended to the overall nonvalvular atrial fibrillation population.

[Impact of malnutrition on long-term mortality in outpatients with chronic heart failure]. / Influencia de la desnutrición sobre la mortalidad a largo plazo en pacientes ambulatorios con insuficiencia cardiaca crónica.

BACKGROUND: Undernutrition is common among acute heart failure patients and its prognosis impact has been established. The prognosis role of undernutrition among chronic heart failure patients is not known. Objetive:The aim of this study were to evaluate the influence of nutritional status on long-term mortality in patients with chronic hear failure. METHODS: 304 consecutively patients attended in our Heart failure Unit from November 2011 to November 2016 were prospectively analysed. A global nutritional assessment was performed and the states of undernutrition and at risk of malnutrition were assessment by the Mini Nutritional Assessment test. Their possible independent association with mortality was analyzed by Cox multivariate analysis. RESULTS: The mean age was 74.6 ± 10.1 years, 41.1% were female and the most frequent aetiology was ischemic heart disease (39.1%). 11.5% of the patients were classified as undernourished and 38.2% were classified as at risk of malnutrition. The remaining 50.3% were classified by the MNA as adequate nutritional status. After 28 months (median of follow-up), mortality was 68.9%, 33.3% and 15.2%, respectively (Log-rank, p < 0.001). When Cox multivariate analysis was performed, the state of undernutrition was an independent predictor of mortality (Hazard ratio 2.73; 95% confidence interval, 1.55-4.81; p < 0.001). CONCLUSIONS: The prevalence of undernutrition and risk of malnutrition reaches high levels in chronic heart failure patients. Moreover, the state of undernutrition by Mini Nutritional Assessment score is an independent predictor of mortality in these patients.

[Total cholesterol levels predict in-hospital mortality in patients with acute heart failure aged 70 years or older]. / El colesterol total predice la mortalidad intrahospitalaria en pacientes de 70 años o mayores hospitalizados por insuficiencia cardiaca aguda.

INTRODUCTION AND PURPOSE: Lower total cholesterol (TC) levels have been associated with increased mortality In both acute and chronic heart failure (HF) patients. The present study sought to evaluate the impact of TC levels on in-hospital mortality in patients with acute HF aged 70 years or older. METHODS: Patients were divided into 3 groups based on TC (mg/dL) quartiles (Q) as follow: Q1 (CT≤125), Q2-Q3 (CT 126-174), Q4 (CT≥175). Multivariate logistic regression analysis was performed to assess the association of each variable with hypocholesterolaemia and in-hospital mortality. RESULTS: The analysis included 301 patients with acute HF. The mean age was 79.3±5.5 years, and 51.2% of patients had HF with depressed systolic function, and the most frequent aetiology was ischaemic heart disease (40.9%). Higher C-reactive protein levels, lower levels of serum albumin and haemoglobin, and lower left ventricle ejection fraction were independently associated with hypocholesterolaemia. There 26 deaths (8.6% of the series) during hospitalization. In-hospital mortality decreased in a stepwise fashion with increasing quartile of TC: Q1 14.3%, Q2-Q3 8.7% and Q4 2.7% (P=.04), and was independently associated with higher serum creatinine levels and lower serum albumin and TC levels. CONCLUSIONS: Lower TC levels independently predict increased in-hospital mortality risk in older patients with acute HF. A higher inflammatory activity, associated with a lower total cholesterol in this clinical setting may explain the inverse relationship between cholesterol and mortality.

[Assessment of body composition and prognosis in chronic heart failure. Beyond the "obesity paradox"]. / Valoración de la composición corporal y su influencia pronóstica en insuficiencia cardiaca crónica. Más allá de la «paradoja de la obesidad¼.

OBJECTIVE: It is unknown the influence of body composition in the inverse relationship of mortality with overweight and obesity in heart failure patients. METHODS: 234 patients with chronic heart failure were evaluated. Body mass index, tricipital skinfold thickness, brachial muscle circumference and body fat percentage determined by bioelectrical impedance analysis were measured. The influence of previous anthropometric variables on total mortality was analyzed. RESULTS: Mean follow-up was 21±10.7 months. We observed an inverse relationship of total mortality with body mass index (hazard ratio=0.91, 95% confidence interval, 0.87-0.96; P<.001), with body fat estimated by the tricipital skinfold thickness (hazard ratio=0.95, 95% confidence interval, 0.92-0.99; P=.013) and the fat percentage obtained by bioelectrical impedance analysis (hazard ratio=0.96; 95% confidence interval, 0.93-0.99; P=.007) and with muscle mass estimated by the brachial muscle circumference (hazard ratio=0.87; 95% confidence interval,0.81-0.94; P=.001). Only brachial muscle circumference maintained its prognostic significance in multivariate analysis that included different anthropometric measurements (hazard ratio=0.88, 95% confidence interval 0.77-0.99; P=.035). Finally we found a positive linear correlation between the values of body mass index with tricipital skinfold thickness, fat percentage and brachial muscle circumference. CONCLUSIONS: The muscle mass of patients with heart failure, estimated by the brachial muscle circumference, is associated inversely with overall mortality. The correlation between values of brachial muscle circumference with the body mass index would explain the "obesity paradox" observed.

Nutritional Intervention in Malnourished Hospitalized Patients with Heart Failure.

BACKGROUND AND AIMS: Hospitalized patients with heart failure who are malnourished present a worse prognosis than those with an adequate nutritional status. We undertook this study to assess whether a nutritional intervention in malnourished hospitalized patients with heart failure benefits morbidity and mortality. METHODS: A multicenter, randomized, controlled clinical trial was conducted. A total of 120 malnourished hospitalized patients due to acute heart failure were randomised to conventional heart failure treatment or conventional heart failure treatment combined with an individualized nutritional intervention. The primary endpoint of this study was a composite of all-cause death or readmission for worsening of HF, with a maximum follow-up of 12 months. Analysis was by intention to treat. RESULTS: Recruitment was stopped early according to the study protocol after completing the follow-up of the first 120 patients enrolled (59 in the intervention group and 61 in the control group). Both groups were homogeneous in baseline characteristics. At 12 months, the primary outcome occurred in 27.1% of patients in the intervention group and in 60.7% of patients in the control group (hazard ratio 0.45; 95% confidence interval [CI], 0.19-0.62, p = 0.0004). In total, 20.3% of patients died in the intervention group and 47.5% in the control group (hazard ratio 0.37, 95% CI, 0.19-0.72, p = 0.003). Readmission due to heart failure was also lower in the intervention group (10.2 vs. 36.1%, p = 0.001). CONCLUSION: Nutritional intervention in malnourished hospitalized patients with heart failure reduces the risk of death from any cause and the risk of readmission for worsening of heart failure (ClinicalTrial.govNCT01472237).

Rationale and design of PICNIC study: nutritional intervention program in hospitalized patients with heart failure who are malnourished.

INTRODUCTION AND OBJECTIVES: Hospitalized patients with heart failure who are malnourished present a worse prognosis than those with an adequate nutritional status. It is unknown whether a nutritional intervention can modify the prognosis of these patients. The aim of this study is to assess the efficacy of a nutritional intervention on morbidity and mortality in hospitalized patients with heart failure who are malnourished. METHODS: PICNIC is a multicentre, randomized, controlled trial in which hospitalized patients with heart failure and malnutrition, as defined by the Mini Nutritional Assessment, are randomly assigned to conventional management of heart failure or conventional management of heart failure and an individualized nutritional intervention consisting of 3 points: optimization of diet, specific recommendations, and prescription, if deemed necessary, of nutritional supplements. A sample size of 182 patients for a maximum follow-up of 12 months has been estimated. The primary endpoint is time to death from any cause or rehospitalization because of heart failure. Analysis is by intention to treat. CONCLUSIONS: PICNIC study will determine the prognostic impact of a nutritional intervention in hospitalized patients with heart failure who are malnourished.

Valoración de la composición corporal y su influencia pronóstica en insuficiencia cardiaca crónica. Más allá de la «paradoja de la obesidad¼ / Assessment of body composition and prognosis in chronic heart failure. Beyond the "obesity paradox"

Resumen Objetivo Se desconoce la influencia pronóstica que la composición corporal guarda en la relación inversa de la mortalidad con el sobrepeso y la obesidad en pacientes con insuficiencia cardiaca. Método Se evaluó a 234 pacientes ambulatorios con insuficiencia cardiaca. Se determinaron el índice de masa corporal, el pliegue tricipital, el perímetro muscular braquial y el porcentaje de grasa corporal evaluado mediante impedanciometría bioeléctrica. Se analizó la influencia sobre la mortalidad total de las variables antropométricas citadas. Resultados El seguimiento medio fue 21 ± 10.7 meses. Se observó una relación inversa de la mortalidad total con el índice de masa corporal (hazard ratio = 0.91; intervalo confianza del 95%, 0.87-0.96; p < 0.001), con la masa grasa estimada por el pliegue tricipital (hazard ratio = 0.95; intervalo confianza del 95%, 0.92-0.99; p = 0.013) y por el porcentaje graso obtenido mediante impedanciometría (hazard ratio = 0.96; intervalo confianza del 95%,0.93-0.99; p = 0.007) y con la masa muscular estimada mediante el perímetro muscular braquial (hazard ratio = 0.87; intervalo confianza del 95%, 0.81-0.94; p = 0.001). Solo el perímetro muscular braquial mantuvo su influencia pronóstica en el análisis multivariante que incluyó a las diferentes medidas antropométricas (hazard ratio = 0.88; intervalo confianza del 95%, 0.77-0.99; p = 0.035). Finalmente, se observó una correlación lineal positiva entre los valores del índice de masa corporal con los del pliegue tricipital, porcentaje graso y perímetro muscular braquial. Conclusiones La masa muscular del paciente con insuficiencia cardiaca, estimada mediante el perímetro muscular braquial, se asocia de manera inversa con la mortalidad global. La correlación de sus valores con los del índice de masa corporal explicaría la «paradoja de la obesidad¼ observada.

Abstract Objective It is unknown the influence of body composition in the inverse relationship of mortality with overweight and obesity in heart failure patients. Methods 234 patients with chronic heart failure were evaluated. Body mass index, tricipital skinfold thickness, brachial muscle circumference and body fat percentage determined by bioelectrical impedance analysis were measured. The influence of previous anthropometric variables on total mortality was analyzed. Results Mean follow-up was 21 ± 10.7 months. We observed an inverse relationship of total mortality with body mass index (hazard ratio = 0.91, 95% confidence interval, 0.87-0.96; P<.001), with body fat estimated by the tricipital skinfold thickness (hazard ratio = 0.95, 95% confidence interval, 0.92-0.99; P=.013) and the fat percentage obtained by bioelectrical impedance analysis (hazard ratio = 0.96; 95% confidence interval, 0.93-0.99; P=.007) and with muscle mass estimated by the brachial muscle circumference (hazard ratio = 0.87; 95% confidence interval,0.81-0.94; P=.001). Only brachial muscle circumference maintained its prognostic significance in multivariate analysis that included different anthropometric measurements (hazard ratio = 0.88, 95% confidence interval 0.77-0.99; P=.035). Finally we found a positive linear correlation between the values of body mass index with tricipital skinfold thickness, fat percentage and brachial muscle circumference. Conclusions The muscle mass of patients with heart failure, estimated by the brachial muscle circumference, is associated inversely with overall mortality. The correlation between values of brachial muscle circumference with the body mass index would explain the “obesity paradox” observed.