Effects of Trimetazidine on Right Ventricular Function and Ventricular Remodeling in Patients with Pulmonary Artery Hypertension: A Randomised Controlled Trial.

BACKGROUND: Pulmonary artery hypertension (PAH) is a chronic and progressive disease. Although current therapy has improved the disease prognosis, PAH has a poor survival rate. The key feature leading to disease progression and death is right ventricular (RV) failure. METHODS AND RESULTS: We assessed the role of trimetazidine, a fatty acid beta-oxidation (FAO) inhibitor, in right ventricular function, remodeling, and functional class in PAH patients, with a placebo-controlled double-blind, case-crossover trial. Twenty-seven PAH subjects were enrolled, randomized, and assigned to trimetazidine or placebo for three months and then reallocated to the other study arm. The primary endpoint was RV morphology and function change after three months of treatment. Secondary endpoints were the change in exercise capacity assessed by a 6 min walk test after three months of treatment and the change in pro-BNP and Galectin-3 plasma levels after three months. Trimetazidine use was safe and well-tolerated. After three months of treatment, patients in the trimetazidine group showed a small but significant reduction of RV diastolic area, and a substantial increase in the 6 min walk distance (418 vs. 438 mt, p = 0.023), without significant changes in biomarkers. CONCLUSIONS: A short course of trimetazidine is safe and well-tolerated on PAH patients, and it is associated with significant increases in the 6MWT and minor but significant improvement in RV remodeling. The therapeutic potential of this drug should be evaluated in larger clinical trials.

Effects of DPP4 Inhibitor in Platelet Reactivity and Other Cardiac Risk Markers in Patients with Type 2 Diabetes and Acute Myocardial Infarction.

BACKGROUND: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers. METHODS: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint). RESULTS: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity (p = 0.51) between the DPP-4i (8.00 {-65.00; 63.00}) and placebo (-14.00 {-77.00; 52.00}) groups, as well in mean BNP levels (p = 0.14) between DPP-4i (-36.00 {-110.00; 15.00}) and placebo (-13.00 {-50.00; 27.00}). There was no difference between groups in cardiac adverse events. CONCLUSIONS: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.

Increased N-terminal Pro-B-Type Natriuretic Peptide during Extracorporeal Life Support Is Associated with Poor Outcome in Neonates with Congenital Diaphragmatic Hernia.

OBJECTIVES: To evaluate the prognostic information derived from the daily measurements of N-terminal pro-B-type natriuretic peptide (proBNP) in neonates with congenital diaphragmatic hernia undergoing extracorporeal life support (ECLS). STUDY DESIGN: Plasma proBNP was prospectively measured daily during the first week of ECLS using an electrochemiluminescence immunoassay. Patients (n = 63) were allocated according to outcome: survivors (group 1, n = 35); nonsurvivors with successful weaning (defined as survival for >12 hours after ECLS discontinuation) (group 2, n = 16); nonsurvivors with unsuccessful weaning (group 3, n = 12). ProBNP kinetics were compared using Kruskal-Wallis testing and correlated with pulmonary hypertension and cardiac dysfunction on echocardiography using the Spearman correlation coefficient. RESULTS: Infants in group 3 presented significantly higher proBNP values from day 3 to day 6 compared with group 1 and 2. Overall mortality among patients with the highest proBNP values on day 1 was 30.6% compared with 63% in those patients with at least 1 higher value on day 2 to day 7. In patients with a late increase (day 4 to day 7) in proBNP the mortality was 70%, compared with 32.6% in those with proBNP below the value on day 1. Weaning failure was 35% in patients with a late increase and 11.6% in those without a late increase. ProBNP correlated significantly with pulmonary hypertension and cardiac dysfunction before and during ECLS. CONCLUSIONS: Absolute proBNP values are associated with weaning failure but not overall mortality in neonates with congenital diaphragmatic hernia undergoing ECLS. Echocardiographic findings correlate well with proBNP values.

Prenatal Particulate Matter (PM) Exposure and Natriuretic Peptides in Newborns from Mexico City.

(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.

Predictive capacity of the brain natriuretic peptide in the screening of heart failure in a high altitude population.

BACKGROUND: Heart failure (HF) is growing in importance as a significant cause of disease and mortality. When It is suspected, it can be ruled out if BNP values are below 100 pg/mL. Diagnostic certainty can be obtained if echocardiogram shows reduced ejection fraction, diastolic dysfunction or right-sided heart disease. Physiological changes at high altitude are known to affect BNP values. This study pretends to evaluate BNP values when used for HF diagnosis in Huancayo, Perú, a high altitude population located at 3,250 m above sea level. METHODS: This is a cross-sectional, diagnostic test type study. A total of 83 medical charts of patients with suspected HF, admitted to the Emergency Room and Internal Medicine Service of Ramiro Prialé Prialé National Hospital, were reviewed. Data processing was performed with SPSS program for Windows version 21.0. Pearson's Chi Square test was used for categorical variables analysis and ANOVA for continuos variables. P values under 0.05 were considered significant. RESULTS AND CONCLUSIONS: Medium age was 74 years. Patient's characteristics that were associated with confirmed HF and high BNP levels were the following: presence of fatigue, night cough, elevated heart rate, shortness of breath, history of lung fibrosis and decreased oxygen arterial saturation (p < 0.05) Pulmonary hypertension, mitral and tricuspid regurgitation, and cor pulmonale were also associated with higher BNP levels. Most subjects had BNP values >100 pg/mL, with low specificity for HF diagnosis (11.5 %). Individuals without heart failure had mean BNP values above 300 pg/mL; while individuals with cor pulmonale had a mean of 975 pg/mL. BNP values were high in patients with or without HF. A cut-off point of ≥130pg/mL is proposed to increase specificity. The predictive capacity of BNP for HF identification at this high altitude population is low because of a high number of false positive results.

Biomarkers assessment in patients with Chagas disease and systemic arterial hypertension.

Chagas disease (ChD) and systemic arterial hypertension (SAH) are two severe comorbidities that lead to mortality and a reduction in people's quality of life, with an impact on public health. The aim of this study was to quantify the biomarkers of cardiac injury in patients with ChD and SAH. Eighty patients were divided into four groups: 20 hypertensive patients, 20 ChD-hypertensive patients, 20 ChD patients, and 20 normotensive volunteers; all of them came from outpatient's public health services. Among the evaluated markers for cardiac lesions (creatine kinase, creatine kinase-MB isoform, myoglobin, high-sensitive cardiac troponin T[hs-cTnT], B-type natriuretic peptide [BNP], and C-reactive protein), hs-cTnT and BNP were the most appropriate. Importantly, our results showed that the cut off point for hs-cTnT could be < 0.007 ng/mL, which could lead to the early detection of myocardial lesions. The BNP and hs-cTnT levels were high only in the ChD and ChD-hypertensive patient groups, suggesting that Chagas' disease may play an important role in the increase of these biomarkers. ChD patients, hypertensive or not, with cardiac or cardiodigestive involvement presented significantly higher values of hs-cTnT (p < 0.001) and BNP (p = 0.001) than ChD patients with indeterminate and digestive forms, which strengthens the validation of these markers for the follow-up of clinical cardiac form of ChD. This study suggests that the BNP and hs-cTnT can be used as possible indirect biomarkers of cardiac damage. In addition, the reference values of these biomarkers in Chagas and hypertensive cardiomyopathies should be better understood with further studies.

B-type natriuretic peptide testing in the emergency setting for managing acute dyspnea. / Péptido natriurético tipo B para manejo de disnea aguda en urgencias.

INTRODUCTION: The performance of B-type natriuretic peptide to accurately diagnose dyspnea of cardiac origin has been widely proved. However, its impact in clinical practice is less clear. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews including five studies overall, of which all were randomized trials. We concluded the use of B-type natriuretic peptide for the management of acute dyspnea in the emergency setting probably leads to a small reduction in the need for hospitalization. Additionally, it may slightly reduce mortality and intensive care unit admission, but the certainty of the evidence is low.

INTRODUCCIÓN: La exactitud diagnóstica del péptido natriurético cerebral (brain natriuretic peptide - BNP) para diferenciar el origen cardiogénico en pacientes con disnea aguda ha sido probada. Sin embargo, existe poca claridad en relación al impacto que tiene su incorporación en la práctica clínica. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron cinco estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que la incorporación de BNP en el manejo de pacientes con disnea aguda probablemente disminuye levemente la necesidad de hospitalización. Además, podría disminuir levemente la mortalidad y hospitalizaciones en unidad de cuidados intensivos.

Correlation between NT-proBNP levels and the maximun vasoactive-inotropic score in the first 24 hours post-intervention of cardiac surgery.

Introduction: The clinical utility of brain natriuretic peptide (NT-proBNP) as a prognostic marker in pediatric patients with heart failure is controversial. The maximum vasoactive inotropic score at 24 h after cardiac surgery in pediatric patients is an important predictor of morbidity and postoperative mortality. Objective: To determine if there is a correlation between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours after cardiac surgery in pediatric patients seen in the Intensive Care Unit. Material and methods: An analytical cross-sectional study. A Spearman correlation analysis (rs) was performed between the serum level of NT-proBNP and the maximum inotropic score both taken at 24 hours postoperatively. A value of p < 0.05 was considered statistically significant. Results: 40 patients were included, 52.5% to the male sex, 72.5% were older than 1 year of age at the time of surgery. A low correlation (rs = 0.26) was found between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours, this correlation was not statistically significant (p = 0.09). Conclusions: To our understanding, the present study is the first to investigate whether there is a correlation between these markers, so our results could set an important precedent that marks the beginning of multiple investigations in our critically ill patients in order to establish new diagnostic, prognostic and therapeutic approaches.

Introducción: La utilidad clínica del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes pediátricos con falla cardíaca es controversial. El puntaje inotrópico vasoactivo 24 horas después de la operación cardíaca en pacientes pediátricos es un importante predictor de morbilidad y mortalidad posoperatoria. Objetivo: Determinar si existe correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo a las 24 horas posteriores a la intervención cardíaca en pacientes pediátricos atendidos en una unidad de terapia intensiva. Material y métodos: Estudio transversal analítico. Se realizó un análisis de correlación de Spearman (rs) entre la cifra sérica de NT-proBNP y el puntaje inotrópico máximo tomados ambos a las 24 horas del postoperatorio. Se consideró estadísticamente significativo un valor de p < 0.05. Resultados: Se incluyó a 40 pacientes, 52.5% del sexo masculino, 72.5% era mayor de un año de edad al momento de la operación. Se encontró una baja correlación (rs = 0.26) entre las concentraciones séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo a las 24 horas; dicha correlación no fue estadísticamente significativa (p = 0.09). Conclusiones: Este estudio es el primero en investigar la correlación entre estos marcadores y los resultados podrían sentar un antecedente que marque el inicio de múltiples investigaciones, con la finalidad de establecer nuevas herramientas diagnósticas, pronósticas y terapéuticas.

Correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo en las primeras 24 horas después de una intervención de cirugía cardíaca / Correlation between NT-proBNP levels and the maximun vasoactive-inotropic score in the first 24 hours post-intervention of cardiac surgery

Resumen Introducción: La utilidad clínica del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes pediátricos con falla cardíaca es controversial. El puntaje inotrópico vasoactivo 24 horas después de la operación cardíaca en pacientes pediátricos es un importante predictor de morbilidad y mortalidad posoperatoria. Objetivo: Determinar si existe correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo a las 24 horas posteriores a la intervención cardíaca en pacientes pediátricos atendidos en una unidad de terapia intensiva. Material y métodos: Estudio transversal analítico. Se realizó un análisis de correlación de Spearman (rs) entre la cifra sérica de NT-proBNP y el puntaje inotrópico máximo tomados ambos a las 24 horas del postoperatorio. Se consideró estadísticamente significativo un valor de p menor que 0.05. Resultados: Se incluyó a 40 pacientes, 52.5% del sexo masculino, 72.5% era mayor de un año de edad al momento de la operación. Se encontró una baja correlación (rs = 0.26) entre las concentraciones séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo a las 24 horas; dicha correlación no fue estadísticamente significativa (p = 0.09). Conclusiones: Este estudio es el primero en investigar la correlación entre estos marcadores y los resultados podrían sentar un antecedente que marque el inicio de múltiples investigaciones, con la finalidad de establecer nuevas herramientas diagnósticas, pronósticas y terapéuticas.

Abstract Introduction: The clinical utility of brain natriuretic peptide (NT-proBNP) as a prognostic marker in pediatric patients with heart failure is controversial. The maximum vasoactive inotropic score at 24 h after cardiac surgery in pediatric patients is an important predictor of morbidity and postoperative mortality. Objective: To determine if there is a correlation between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours after cardiac surgery in pediatric patients seen in the Intensive Care Unit. Material and methods: An analytical cross-sectional study. A Spearman correlation analysis (rs) was performed between the serum level of NT-proBNP and the maximum inotropic score both taken at 24 hours postoperatively. A value of p less 0.05 was considered statistically significant. Results: 40 patients were included, 52.5% to the male sex, 72.5% were older than 1 year of age at the time of surgery. A low correlation (rs = 0.26) was found between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours, this correlation was not statistically significant (p = 0.09). Conclusions: To our understanding, the present study is the first to investigate whether there is a correlation between these markers, so our results could set an important precedent that marks the beginning of multiple investigations in our critically ill patients in order to establish new diagnostic, prognostic and therapeutic approaches.

Falla cardíaca en pacientes pediátricos. Fisiopatología y tratamiento. Parte II / Heart failure in paediatric patients: pathophysiology and treatment. Part II

Resumen La falla cardiaca en una patología poco reconocida en la edad pediátrica y tiene una alta tasa de mortalidad al no ser diagnosticada en forma temprana. Se hace una revisión del diagnóstico, la estratificación y el manejo actual de la falla cardiaca en niños y se mencionan las nuevas terapias actualmente en investigación.

Abstract Heart failure is a little known condition at paediatric age, and has a high mortality rate on not being diagnosed early. A review is presented on its diagnosis, stratification, and current management of heart failure in children, as well the new therapies currently under investigation.

Índice de asincronía/péptido natriurético cerebral como predictor de éxito en extubación en pacientes con trauma de tórax / Index asynchrony/brain natriuretic peptide as a predictor of successful extubation in patients with chest trauma / Índice assincronia/peptido natriurético cerebral como preditor de sucesso na extubação de pacientes com traumatismo de toráx

Resumen: Antecedentes: El trauma de tórax (TT) requiere estrategias de ventilación mecánica (VM) específicas y el retiro es complejo; la asincronía ventilatoria (AV) aumenta la morbimortalidad, situación no descrita en la población mexicana. Objetivo: Correlacionar el índice de asincronía (IA)/péptido natriurético cerebral (BNP) (IA/BNP), con el resultado de la extubación en pacientes con TT. Material y métodos: Se realizó un estudio longitudinal en unidades de cuidados intensivos (UCI) con 30 participantes con variables de estudio demográficas, tipo de TT, IA, BNP pre- (BNP1) y postdecanulación (BNP2), IA/BNP, escalas predictoras de extubación. Desenlace: éxito o fracaso en la extubación (reintubación en las primeras 48 horas). Resultados: Los participantes representaron 96.7% masculino, 3.3% femenino; edad: 34.4 ± 11.2 años; éxito en el retiro de la VM: 70%; tipo de TT: neumotórax/hemotórax 40%, hemotórax aislado 16.7%, neumotórax 10%, tórax inestable/contusión pulmonar 10%, otras variedades de lesión 23.3%. BNP1: 44.2 ± 23.2 pg/dL, BNP2: 67 ± 49 pg/dL, IA: 13 ± 2%, IA/BNP: 0.28 ± 0.15, índice de ventilación rápida y superficial (IVRS): 83.2 ± 13.1, MIP: -24.2 ± 3.07, P 0.1-3.9 ± 0.7. La correlación de Pearson para IA y BNP1 fue r = 0.71, el índice de determinación: r2 = 0.50, con significancia p < 0.001, a un intervalo de confianza (IC) 95%; para IA y BNP2: r = 0.83, r2 = 0.68, p < 0.001, IC 95%. La correlación de Spearman para IA/BNP y fallo: r = 0.62, el índice de determinación: r2 = 0.39, con significancia p < 0.001, a un intervalo de confianza (IC) 95%; para IVRS y fallo: r = 0.31, r2 = 0.09, p < 0.094, IC 95%. IA/BNP < 0.14 se correlacionó con fallo en la extubación. Conclusiones: Se demostró que el IA/BNP < 0.14 es un marcador confiable como predictor del fallo en el retiro de la VM en las primeras 48 horas, comparado con el tradicional IVRS, el cual no demostró significancia estadística.

Abstract: Background: Chest trauma (CT) requires specific mechanical ventilation (MV) strategies; weaning is a complex situation. Ventilatory asynchrony (VA) implies an increased morbimortality, not described in the Mexican population. Aim: To correlate the index of asynchrony (IA)/brain natriuretic peptide (BNP), (IABNP), with the result of extubation in patients with chest trauma. Material and methods: A longitudinal study was done in intensive care units (ICU), 30 patients were included; the following variables were evaluated: demographics, type of trauma, IA, BNP before (BNP1) and after (BNP2) extubation, as well as IA/BNP as a scale to predict extubation. Endpoint: success or failure of the extubation (reintubation in next 48 hours). Results: The study population was 96.7% masculine, 3.3% female; age: 34.4 ± 11.2 years. Successful withdrawal of MV was 70%. Type of trauma was pneumo/hemothorax 40%, hemothorax 16.7%, pneumothorax 10%, flail chest/pulmonary contusion 10%, other types 23.3%. BPN1: 44.2 ± 23.2 pg/dL, BNP2: 67 ± 49 pg/dL, IA: 13 ± 2%, IA/BNP: 0.28 ± 0.15, rapid surface respiration index (IVRS): 83.2 ± 13.1, maximum inspiration pressure (MIP): -24.2 ± 3.07, P 0.1-3.9 ± 0.7. Pearson correlation for IA and BNP1 was r = 0.71, the determination index: r2= 0.50, with significance p < 0.001, confidence interval (CI) 95%; for AI and BNP2: r = 0.83, r2 = 0.68, p < 0.001, CI 95%. Spearman correlation for IA/BNP and failure: r = 0.62, and determination index: r2 = 0.39, with significance p < 0.001, CI 95%; for RSSR and failure: r = 0.31, r2 = 0.09, with p < 0.094, CI 95%. IA/BNP < 0.14 was related with failure at extubation. Conclusions: IA/BNP < 0.14 was a predictive marker for failure of weaning MV in the first 48 hours compared with the traditional RSRR, which was not statistically significant.

Resumo: Introdução: O trauma torácico (TT) requer estratégias específicas de ventilação mecânica (VM) e a retirada é complexa; a assincronia ventilatória (AV) aumenta a morbimortalidade; situação não descrita na população mexicana. Objetivo: Correlacionar o índice de assincronia (IA)/peptídeo natriurético cerebral (BNP) (IA/BNP) com o resultado da extubação em pacientes com TT. Material e métodos: Realizou-se um estudo longitudinal em Unidades de Terapia Intensiva (UTI) com 30 participantes com variáveis de estudo: demográficos, tipo de TT, IA, BNP pré (BNP1) e pós-decanulação (BNP2), IA/BNP, escalas preditivas de extubação. Desenlace: sucesso ou falha na extubação (reintubação nas primeiras 48 horas). Resultados: Os participantes representados: 96.7% homens, 3.3% mulheres, idade 34.4 ± 11.2 anos, sucesso da retirada da VM 70%; Tipo TT: pneumotórax/hemotórax 40%, hemotórax isolado 16.7%, pneumotórax 10%, tórax instável/contusão pulmonar 10%, outras variedades de lesão 23.3%. BNP1 44.2 ± 23.2 pg/dL, BNP2 67 ± 49 pg/dL, IA13 ± 2%, IA/BNP 0.28 ± 0.15, índice de ventilação rápida e superficial (IVRS) 83.2 ± 13.1, MIP -24.2 ± 3.07, P 0.1-3.9 ± 0.7. A correlação de Pearson para IA e BNP1 foi: r = 0.71, o índice de determinação r2 = 0.50 com significância p < 0.001, intervalo de confiança (IC) 95%, para IA e BNP2: r = 0.83, r2 = 0.68, p < 0.001, IC 95%. A correlação de Spearman para IABNP e falha r = 0.62, índice de determinação r2 = 0.39, com significância p < 0.001, intervalo de confiança (IC) 95%, para IVRS e falha r = 0.31, r2 = 0.09, p < 0.094, IC 95%. IA/BNP < 0.14 correlacionou-se com falha na extubação. Conclusões: Demonstrouse que o índice AI/BNP < 0.14 é um marcador confiável como preditor de falha na remoção de VM nas primeiras 48 horas em comparação com a tradicional IVRS, que não apresentou significância estatística.

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. OBJECTIVES: To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. METHODS: Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10-9M, 10-7M and 10-5M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. RESULTS: Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10-5M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). CONCLUSIONS: Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF.

INTERACTING DISCIPLINES: Cardiac natriuretic peptides and obesity: perspectives from an endocrinologist and a cardiologist.

Since their discovery in 1981, the cardiac natriuretic peptides (cNP) atrial natriuretic peptide (also referred to as atrial natriuretic factor) and brain natriuretic peptide have been well characterised in terms of their renal and cardiovascular actions. In addition, it has been shown that cNP plasma levels are strong predictors of cardiovascular events and mortality in populations with no apparent heart disease as well as in patients with established cardiac pathology. cNP secretion from the heart is increased by humoral and mechanical stimuli. The clinical significance of cNP plasma levels has been shown to differ in obese and non-obese subjects. Recent lines of evidence suggest important metabolic effects of the cNP system, which has been shown to activate lipolysis, enhance lipid oxidation and mitochondrial respiration. Clinically, these properties lead to browning of white adipose tissue and to increased muscular oxidative capacity. In human association studies in patients without heart disease higher cNP concentrations were observed in lean, insulin-sensitive subjects. Highly elevated cNP levels are generally observed in patients with systolic heart failure or high blood pressure, while obese and type-2 diabetics display reduced cNP levels. Together, these observations suggest that the cNP system plays a role in the pathophysiology of metabolic vascular disease. Understanding this role should help define novel principles in the treatment of cardiometabolic disease.

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

AIM: To assess residual diuresis and diverse variables according to body mass index (BMI). METHODS: Cross-sectional study (n = 57), with 3 groups. Group A: BMI < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro-BNP, Troponin T, leptin and insulin levels are expressed as median and ranges (r). RESULTS: Albumin (g/dL): GA vs GC, 3.70 (r2.20-4.90) vs 3.85 (r3.40-4.90), P = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840). Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, 3.81 (r0.78-69.60) vs GC, 32.80 (r0.78-124.50), P < 0.001. Insulin (µU/mL): GA vs GB, 7 (r2-44) vs 11.50 (r4-38), P = 0.02; GA vs GC, 7 (r2-44) vs 19.5 (r5-155), P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations: GC, Insulin-UF: ρ = 0.53; P = 0.03; TroponinT-diuresis: ρ = -0.48, P < 0.05; Pro-BNP-diuresis: ρ = -0.39, P < 0.01; Troponin T-ProBNP: ρ = 0.77, P < 0.0001; albumin-Troponin T: ρ = -0.66, P < 0.0001; albumin-ProBNP: ρ = -0.44, P < 0.05. CONCLUSION: High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.

The effect of preoperative nutritional status on postoperative outcomes in children undergoing surgery for congenital heart defects in San Francisco (UCSF) and Guatemala City (UNICAR).

OBJECTIVE: The objective of this study was to determine the association between preoperative nutritional status and postoperative outcomes in children undergoing surgery for congenital heart defects (CHD). METHODS: Seventy-one patients with CHD were enrolled in a prospective, 2-center cohort study. We adjusted for baseline risk differences using a standardized risk adjustment score for surgery for CHD. We assigned a World Health Organization z score for each subject's preoperative triceps skin-fold measurement, an assessment of total body fat mass. We obtained preoperative plasma concentrations of markers of nutritional status (prealbumin, albumin) and myocardial stress (B-type natriuretic peptide [BNP]). Associations between indices of preoperative nutritional status and clinical outcomes were sought. RESULTS: Subjects had a median (interquartile range [IQR]) age of 10.2 (33) months. In the University of California at San Francisco (UCSF) cohort, duration of mechanical ventilation (median, 19 hours; IQR, 29 hours), length of intensive care unit stay (median, 5 days; IQR 5 days), duration of any continuous inotropic infusion (median, 66 hours; IQR 72 hours), and preoperative BNP levels (median, 30 pg/mL; IQR, 75 pg/mL) were associated with a lower preoperative triceps skin-fold z score (P < .05). Longer duration of any continuous inotropic infusion and higher preoperative BNP levels were also associated with lower preoperative prealbumin (12.1 ± 0.5 mg/dL) and albumin (3.2 ± 0.1; P < .05) levels. CONCLUSIONS: Lower total body fat mass and acute and chronic malnourishment are associated with worse clinical outcomes in children undergoing surgery for CHD at UCSF, a resource-abundant institution. There is an inverse correlation between total body fat mass and BNP levels. Duration of inotropic support and BNP increase concomitantly as measures of nutritional status decrease, supporting the hypothesis that malnourishment is associated with decreased myocardial function.

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis.

OBJECTIVES: The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND: Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS: We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS: Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS: Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

[The endocrine heart and inflammation]. / El corazón endocrino y el proceso inflamatorio.

The endocrine heart produces the polypeptide hormones Atrial Natriuretic Factor (ANF or ANP) and Brain Natriuretic Peptide (BNP). Through the peripheral actions of these hormones the heart contributes to the regulation of the cardiac preload and afterload. More recently, new functions for these hormones have been described including the modulation of the immune response. Plasma levels of BNP but not those of ANF, increase following an acute rejection episode of a cardiac allotransplant but return to levels pre-rejection with successful treatment. This observation constitutes the first observation leading to characterizing the interactions of BNP with the immune response. Several other pathologies with an inflammatory component are now known to be associated with an increase in the production of BNP. Such an increase is due to an increase in the transcriptional activity of the BNP gene induced by cytokines and related substances. In vitro investigations have shown that an increase in BNP directly modulates immunological activity. Inflammation and hemodynamic changes co-exist in several cardiovascular diseases and therefore it may be beneficial to measure circulating levels of both ANF and BNP as biomarkers of changes in intravascular volume and of changes in intravascular volume plus inflammation, respectively. Changes in plasma ANF, that are relatively larger than those of BNP, might be an indication of hemodynamic deterioration while important changes in circulating BNP could indicate a worsening of the inflammatory process.

Long-term outcomes of pediatric sinus bradycardia.

OBJECTIVES: To delineate the long-term outcomes and mechanisms of pediatric sinus bradycardia. STUDY DESIGN: Participants with sinus bradycardia who were identified from a survey of 432,166 elementary and high school students, were enrolled 10 years after the survey. The clinical course, heart rate variability, and hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) gene were assessed. RESULTS: A total of 104 (male:female was 60:44; prevalence, 0.025%) participants were observed to have sinus bradycardia at age 15.5 ± 0.2 years with a mean heart rate of 48.4 ± 0.4 beats per minute; 86 study participants (83%) responded to clinical assessment and 37 (36%) underwent laboratory assessment. Athletes composed 37.8% of the study participants. During the extended 10-year follow-up, 15 (17%) of the participants had self-limited syncopal episodes, but none had experienced life-threatening events. According to Holter recordings, none of the participants had heart rate <30 beats per minute or a pause longer than 3 seconds. Compared with 67 age- and sex-matched controls, the variables of heart rate based on the spectral and time domain analysis of the participants with sinus bradycardia were all significantly higher, indicating higher parasympathetic activity. The results of mutation analysis were negative in the HCN4 gene in all of our participants. CONCLUSIONS: The long-term outcomes of the children and adolescents with sinus bradycardia identified using school electrocardiographic survey are favorable. Parasympathetic hyperactivity, instead of HCN4 gene mutation, is responsible for the occurrence of sinus bradycardia.

Descenso de los niveles de propéptido natriurético de tipo B-N terminal luego de la reversión de pacientes con fibrilación auricular y función ventricular conservada / NT-Pro-BNP levels performance before and after reversion to sinus rhythm in patients with preserved ventricular function

El objetivo fue comparar los niveles de Pro Péptido Natriurético tipo B-N terminal (Pro-BNP-NT) basales y post reversión en pacientes con fibrilación auricular solitaria (FAS) de comienzo reciente y con función ventricular izquierda conservada. Se determinaron niveles del Pro BNP NT antes y después de su reversión en treinta pacientes con FAS de comienzo reciente y fracción de eyección de ventrículo izquierdo ≥ 50%. Basalmente, los niveles de Pro BNP NT fueron significativamente más elevados respecto a un grupo control sano: 529 pg/ml (157-1763) versus 31.5 pg/ml (24-76), p < 0.0001. Las concentraciones de Pro BNP NT descendieron significativamente luego de la cardioversión de 529 (157-1763) a 318 (98-870) pg/ml, p < 0.001. Los descensos se objetivaron tanto luego de la cardioversión eléctrica como de la obtenida por vía farmacológica, 345 (153-1151) pg/ml a 169 (86-407) pg/ml, p: 0.02 y de 1624 (541-4010) pg/ml a 856 (532-1160) pg/ml, p < 0.001, respectivamente. Este fenómeno se observó fundamentalmente en aquellos con una FAS con duración mayor a 8 horas: 1289 (338-2103) a 410 (169-905) pg/ml, p < 0.001. No se observó correlación entre los cambios de la frecuencia cardíaca y del Pro BNP NT pre y post cardioversión a ritmo sinusal. Se observaron descensos significativos de Pro BNP NT basalmente y post reversión (tanto farmacológica como eléctrica) en pacientes con FA de reciente aparición y función ventricular conservada. Estos descensos fueron más ostensibles a partir de las 8 horas de duración de la arritmia.

Our objective was to evaluate changes of N-terminal pro-BNP (NT-Pro-BNP) levels at baseline and after restoration to sinus rhythm in hemodynamic stable patients with lone atrial fibrillation (LAF) with preserved left ventricular function. NT-Pro-BNP levels were obtained before and after cardioversion in thirty hemodynamic stable patients with LAF and preserved left ventricular function. At baseline levels of NT-Pro BNP levels were significatively higher than a normal control group. NTPro-BNP levels decreased significantly following cardioversion from 529 (157-1763) to 318 (98-870) pg/ml, p < 0.0001. Decreasing of N-terminal pro-BNP concentrations was observed after any mode of cardioversion: electrical or pharmacologic, 345 (153-1151) pg/ml to 169 (86-407) pg/ml, p: 0.02 and from 1624 (541-4010) pg/ml to 856 (532-1160) pg/ml, p < 0.001, respectively. N-terminal pro-BNP decreasing was observed mainly in patients with length of LAF longer than 8 hours: 1289 (338-2103) to 410 (169-905) pg/ml, p < 0.001 but no difference was detected when such length was less than 8 hours: 274 (137-2300) to 286 (82-1440), p = NS. Our study showed that baseline levels of NT-pro-BNP decreased shortly after reversion of patients with LAF to sinus rhythm. This performance occurs predominantly in patients with LAF length of at least eight hours.