Efecto del ejercicio físico sobre el péptido natriurético cerebral en pacientes con insuficiencia cardíaca: una revisión sistemática / Effect of physical exercise on brain natriuretic peptide in patients with heart failure: a systematic review

Resumen El entrenamiento aeróbico (EA) está demostrando ser un tratamiento no farmacológico que genera una mejora en el péptido natriurético cerebral (BNP), lo que disminuye el riesgo de mortalidad del paciente con insuficiencia cardíaca (IC). Sin embargo, no se ha observado el efecto de la alta intensidad, el entrenamiento intervalico o la combinación con contra resistencia (concurrente). En general, el ejercicio físico produce disminuciones en los biomarcadores cardíacos (BNP y NT- proBNP), sugiriendo una mejora general en el perfil neuro-hormonal de los pacientes con IC. Propósito: Revisar la evidencia científica sobre la efectividad de distintas modalidades de ejercicio físico en la disminución del BNP y del NT-proBNP en pacientes con IC. Metodología Esta revisión sistemática se desarrolló con base en los criterios PICOS, se realizó una búsqueda de los artículos científicos mediante bases de datos electrónicas, tales como: "PubMed", "Academic Search Ultimate", "SportDiscus" y "ScienceDirect". Se acceso a estas bases de datos por medio de la plataforma "EBSCO host". Los términos de búsqueda (frase booleana) o palabras clave fueron los siguientes: (''heart failure'') AND ("cardiac rehabilitation" OR "exercise" OR ''trai- ning'') AND ("brain natriuretic peptide" OR "atrial natriuretic peptide") NOT ("animals" OR "rat"). Las búsquedas se realizaron entre enero y marzo de 2020. Resultados: Se revisaron un total de 1623 estudios, donde al final se incluyeron 22 artículos cualitativos para realizar esta revisión sistemática de literatura. Se analizaron un total de 1601 pacientes con IC y se observa una disminución del BNP con el EA entre un 6.7% y un 50.5%. Con respecto al EC, se observa que no hay efectos significativos en la disminución del BNP, ya que se reporta una disminución de tan solo 1% y un incremento de un 67.4%. En relación con el NT-proBNP, se encontraron disminuciones significativas entre un 13.6% y un 71.7% con el EA y entre un 2.5% y un 36.7% con el EC, pero también se encontraron aumentos en esta variable. Conclusiones: Tanto el EA como el EC genera efectos positivos sobre BNP y NT-proBNP en pacientes con IC, en comparación con aquellos que no realizan ningún tipo de ejercicio físico.

Abstract Aerobic training (AE) is proving to be a non-pharmacological treatment that generates an improvement in the cerebral natriuretic peptide (BNP), which reduces the risk of mortality of the patient with heart failure (HF). However, the effect of high intensity, interval training, or combination with resistance training (complex o concurrent) has not been observed. In general, physical exercise produces decreases in cardiac biomarkers (BNP and NT-proBNP), suggesting a general improvement in the neuro-hormonal profile of patients with HF. Objective: To review the scientific evidence on the effectiveness of different physical exercise modalities in decreasing BNP and NT-proBNP in patients with HF. Methodology: This systematic review was developed based on the PICOS criteria, a search for scientific articles was carried out using electronic databases, such as: "PubMed", "Academic Search Ultimate", "SportDiscus" and "ScienceDirect". These databases are accessed through the "EBSCO host" platform. The search terms (Boolean phrase) or keywords were as follows: (''heart failure'') AND ("cardiac rehabilitation" OR "exercise" OR ''training'') AND ("brain natriuretic peptide" OR "atrial natriuretic peptide") NOT ("animals" OR "rat"). The searches were carried out between january and march 2020. Resulted: A total of 1623 studies were reviewed, where in the end 21 qualitative articles were included to carry out this systematic literature review. A total of 1601 patients with HF were analyzed and was observed a decrease in BNP with AD between 6.7% and 50.5%. Regarding the EC, it is observed that there are no significant effects in the decrease of the BNP, since a decrease of only 1% and an increase of 67.4% are reported. In relation to the NT-proBNP, significant decreases were found between 13.6% and 71.7% with the EA and between 2.5% and 36.7% with the EC, but increases were also found in this variable. Conclusions: Both EA and EC generate positive effects on BNP and NT-proBNP in patients with HF, compared to patients who did not do any type of physical exercise.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

Examen clínico y maniobra de valsalva en la insuficiencia cardíaca / Clinical examination and the Valsalva maneuver in heart failure

La evaluación de la congestión en pacientes con insuficiencia cardíaca y fracción de eyección reducida (ICFEr) resulta relevante y estrechamente vinculada al curso clínico. El agregado del comportamiento de la presión arterial durante la maniobra de Valsalva en la cabecera del paciente (VAL) podría mejorar la evaluación clínica de congestión cuando la comparamos con los niveles de NT-proBNP y la estimación de la presión media en la aurícula izquierda por Doppler cardíaco, como subrogantes de congestión. Se realizó un examen clínico con el VAL, un examen de laboratorio y un Doppler cardíaco en 69 pacientes ambulatorios con insuficiencia cardíaca y fracción de eyección ≤ 40% en ritmo sinusal. El score de Framingham ≥ 2 (SFr ≥ 2) se empleó para evaluar congestión clínica. VAL fue clasificado como normal o anormal, el NT-proBNP como bajo (< 1000 pg/ml) o alto (≥ 1000 pg/ml) y la relación entre la velocidad del llenado ventricular rápido y la velocidad del Doppler tisular (E/e') como baja < 15 o alta ≥ 15. Se halló que 13/27 pacientes con SFr ≥ 2 tenían NT-proBNP alto (sensibilidad 62%, especificidad 70% y razón de verosimilitud positiva [LR+] de 2.08, p = 0.01). El agregado del VAL al SFr ≥ 2 mejoró la exactitud diagnóstica (sensibilidad 100%, especificidad 64% y LR+ 2.8 p = 0.0004). Comparado con la E/e', SFr ≥ 2 con VAL anormal mostró sensibilidad 86%, especificidad 56% y LR + 1.86 (p = 0.03). En conclusión, el agregado del comportamiento de la presión durante la maniobra de Valsalva podría mejorar la evaluación clínica de la congestión en la insuficiencia cardíaca.

Congestion in heart failure patients with reduced ejection fraction (HFrEF) is relevant and closely linked to the clinical course. Bedside blood pressure measurement during the Valsalva maneuver (Val) added to clinical examination may improve the assessment of congestion when compared to NT-proBNP levels and left atrial pressure (LAP) estimation by Doppler echocardiography, as surrogate markers of congestion in HFrEF. A clinical examination, LAP and blood tests were performed in 69 HFrEF ambulatory patients with left ventricular ejection fraction ≤ 40% and sinus rhythm. Framingham Heart Failure Score (HFS) was used to evaluate clinical congestion; Val was classified as normal or abnormal, NT-proBNP was classified as low (< 1000 pg/ml) or high (≥ 1000 pg/ml) and the ratio between Doppler early mitral inflow and tissue diastolic velocity was used to estimate LAP and was classified as low (E/e'< 15) or high (E/e' ≥ 15). A total of 69 patients with HFrEF were included; 27 had a HFS ≥ 2 and 13 of them had high NT-proBNP. HFS ≥ 2 had a 62% sensitivity, 70% specificity and a positive likelihood ratio of 2.08 (p=0.01) to detect congestion. When Val was added to clinical examination, the presence of a HFS ≥ 2 and abnormal Val showed a 100% sensitivity, 64% specificity and a positive likelihood ratio of 2.8 (p = 0.0004). Compared with LAP, the presence of HFS ≥ 2 and abnormal Val had 86% sensitivity, 54% specificity and a positive likelihood ratio of 1.86 (p = 0.03). In conclusion, an integrated clinical examination with the addition Valsalva maneuver may improve the assessment of congestion in patients with HFrEF.

Remodelación de cavidades izquierdas en el posoperatorio de retorno venoso pulmonar anómalo total: utilidad del NTProBNP / Left chambers remodeling after repair of TAPVR connection: usefulness of NTProBNP

Resumen: El retorno venoso pulmonar anómalo total se caracteriza por la falla de conexión entre la aurícula primitiva y el retorno venoso pulmonar, este último se conecta al retorno venoso sistémico a través de la persistencia de conexiones embrionarias. En esta patología, el ventrículo izquierdo suele tener un tamaño en el límite inferior de la normalidad, con una aurícula izquierda pequeña y atrófica. En el período posoperatorio las cavidades izquierdas deben manejar todo el retorno venoso pulmonar, lo que podría determinar sobrecarga de estas cavidades. Presentamos dos casos de posoperatorio de retorno venoso pulmonar anómalo total, evaluando la relación entre el tamaño auricular izquierdo y los niveles de péptido natriurético. Se plantea como hipótesis una disfunción en el llenado de cavidades izquierdas como sustrato causal de este fenómeno, teniendo como consecuencia modificaciones adaptativas anatómicas y funcionales. La determinación de los niveles de péptido natriurético podría ser útil en la monitorización de este proceso adaptativo.

Summary: Total anomalous pulmonary venous return is a congenital heart disease characterized by failure of connection between the primitive left atrium and the pulmonary venous return, the latter drains to the systemic venous return trough persistent embryologic connections. In this pathology there is a normal size, but rather small, left ventricle with a small and undeveloped left atrium. In the postoperative period, the left chambers must handle all the pulmonary venous return, which could mean an increased wall stress. The study presents two cases of Total Anomalous Pulmonary Venous Return, and the behavior of left atrial size and natriuretic peptide level after surgery. We set a hypothesis by which a dysfunction in the filling of the left chambers could explain this phenomenon and how this triggers compensatory modifications. Analyzing the level of natriuretic peptide might help monitor this process.

Relationship between Myocardial Extracellular Space Expansion Estimated with Post-Contrast T1 Mapping MRI and Left Ventricular Remodeling and Neurohormonal Activation in Patients with Dilated Cardiomyopathy

OBJECTIVE: Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: Fifty-nine patients with DCM (mean age, 55 +/- 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. RESULTS: The mean LV ejection fraction was 24 +/- 9% and the post-T1 value was 254.5 +/- 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (beta = -0.351, p = 0.016) and the LV mass/volume ratio (beta = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (beta = -0.339, p = 0.017). CONCLUSION: Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.

Current Status of Therapeutic Strategies for Patent Ductus Arteriosus in Very-Low-Birth-Weight Infants in Korea

This study aimed to investigate current therapeutic strategies for patent ductus arteriosus (PDA) in very-low-birth-weight (VLBW) infants in Korea. A total of 2,254 VLBW infants among 2,386 from Korean Neonatal Network cohort born from January 2013 to June 2014 were included. No PDA was seen for 1,206 infants (53.5%) and the infants diagnosed or treated for PDA were 1,048 infants (46.5%). The proportion of infants with PDA was decreased according to the increase in gestational age (GA) and birthweight. Infants with PDA were divided into groups according to the therapeutic strategies of PDA: prophylactic treatment (PT, n = 69, 3.1%), pre-symptomatic treatment (PST, n = 212, 9.4%), symptomatic treatment (ST, n = 596, 26.4%), and conservative treatment (CT, n = 171, 7.6%). ST was the most preferred treatment modality for preterm PDA and the proportion of the patients was decreased in the order of PST, CT, and PT. Although ST was still the most favored treatment in GA or = 32 weeks group [CT vs. PST, OR 5.3, 95% CI 1.56-18.18; CT vs. ST, OR 2.9, 95% CI 1.03-8.13]. A total of 877 infants (38.9%) received pharmacological or surgical treatment about PDA, and 35.5% (801 infants) received pharmacological treatment, mostly with ibuprofen. Seventy-six infants (3.4%) received primary ligation and 8.9% (201 infants) received secondary ligation. Diverse treatment strategies are currently used for preterm PDA in Korea. Further analyses of neonatal outcomes according to the treatment strategies are necessary to obtain a standardized treatment guideline for preterm PDA.

The five-point Likert scale for dyspnea can properly assess the degree of pulmonary congestion and predict adverse events in heart failure outpatients

OBJECTIVES: Proper assessment of dyspnea is important in patients with heart failure. Our aim was to evaluate the use of the 5-point Likert scale for dyspnea to assess the degree of pulmonary congestion and to determine the prognostic value of this scale for predicting adverse events in heart failure outpatients. METHODS: We undertook a prospective study of outpatients with moderate to severe heart failure. The 5-point Likert scale was applied during regular outpatient visits, along with clinical assessments. Lung ultrasound with ≥15 B-lines and an amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) level >1000 pg/mL were used as a reference for pulmonary congestion. The patients were then assessed every 30 days during follow-up to identify adverse clinical outcomes. RESULTS: We included 58 patients (65.5% male, age 43.5±11 years) with a mean left ventricular ejection fraction of 27±6%. In total, 29.3% of these patients had heart failure with ischemic etiology. Additionally, pulmonary congestion, as diagnosed by lung ultrasound, was present in 58% of patients. A higher degree of dyspnea (3 or 4 points on the 5-point Likert scale) was significantly correlated with a higher number of B-lines (p = 0.016). Patients stratified into Likert = 3-4 were at increased risk of admission compared with those in class 1-2 after adjusting for age, left ventricular ejection fraction, New York Heart Association functional class and levels of NT-proBNP >1000 pg/mL (HR = 4.9, 95% CI 1.33-18.64, p = 0.017). CONCLUSION: In our series, higher baseline scores on the 5-point Likert scale were related to pulmonary congestion and were independently associated with adverse events during follow-up. This simple clinical tool can help to identify patients who are more likely to decompensate and whose treatment should be intensified. .

Perioperative cardiovascular evaluation: heads or tails?

When dealing with surgical patients, a perioperative evaluation is essential to anticipate complications and institute measures to reduce the risks. Several algorithms and exams have been used to identify postoperative cardiovascular events, which account for more than 50% of perioperative mortality. However, they are far from ideal. Some of these algorithms and exams were proposed before important advances in cardiology, at a time when pharmacological risk reduction strategies for surgical patients were not available. New biomarkers and exams, such as C-reactive protein, brain natriuretic peptide, and multislice computed tomography have been used in cardiology and have provided important prognostic information. The ankle-brachial index is another significant marker of atherosclerosis. However, specific information regarding the perioperative context of all these methods is still needed. The objective of this article is to evaluate cardiovascular risk prediction models after noncardiac surgery.

Clinical correlation of multiple biomarkers for risk assessment in patients with acute coronary syndrome.

OBJECTIVE: Biochemical markers are useful for the prediction of future cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (ACS). The independent as well as the combined prognostic value of elevated troponin-T, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) on the Thrombolysis In Myocardial Infarction (TIMI) risk score and on the short-term prognosis were evaluated in a cohort of ACS patients. METHODS AND RESULTS: In an unselected, heterogeneous group of 80 patients with ACS (i.e., unstable angina [USA] or non-ST-elevation myocardial infarction [NSTEMI]), the levels of troponin-T, hs-CRP, and NT-pro-BNP were analyzed. The correlation between elevation of different biomarkers with TIMI risk score and their impact on 30-day major adverse cardiac events was sought. The levels of hs-CRP were significantly higher in patients who had angina as their predominant complaint (3.67 mg/dl vs. 1.67 mg/dl: p < 0.01), while levels of NT-pro-BNP was higher in those patients who had any element of heart failure at presentation (2616.39 pg/ml vs. 1068.3 pg/ml; p < 0.01). Troponin-T was highest in patients who had an element of both heart failure and angina at presentation (p < 0.01). The TIMI risk score expectedly had a positive and strong correlation with elevated troponin-T, but had no correlation with elevation of hs-CRP and NT-pro-BNP in isolation. However, when any two biomarkers were elevated, the patients were in the intermediate risk group as per TIMI risk score irrespective of troponin-T-elevation. When all the three biomarkers were elevated, the risk equaled the high-risk category of TIMI risk score. Elevated hs-CRP (3.40 mg/dl vs. 1.38 mg/dl; p < 0.001) and troponin-T (2.37 ng/ml vs. 1.23 ng/ml; p < 0.001) at baseline correlated independently with the occurrence of re-ischemia, while elevated NT-pro-BNP alone correlated significantly with the development of heart failure within 30 days of follow-up (4247.76 pg/ml vs. 1210.86 pg/ml; p < 0.01). The highest risk of death from any cardiovascular cause within 30 days of follow-up was significantly higher when all the three biomarkers were elevated. CONCLUSION: The use of NT-pro-BNP, hs-CRP, and troponin-T in combination appears to add critical prognostic insight to the assessment of patients with ACS.

Impacto da disfunção renal no desempenho do peptídio natriurético cerebral para o diagnóstico de insuficiência cardíaca / The impact of renal dysfunction on the accuracy of serum brain natriuretic peptide levels for the diagnosis of heart failure

Fundamentos: O Peptídeo Natriurético Cerebral (BNP) tem sido utilizado no diagnóstico diferencial de dispnéia na sala de emergência (DSE). Contudo, a sua performance diagnóstica é influenciada por vários fatores, entre eles a disfunção renal(DR). Objetivo: Determinar a influência da disfunção renal na exatidão do BNP para diagnosticar Insuficiência Cardíaca (IC) em pacientes com dispnéia na sala de emergência. Métodos: Análise de 207 atendimentos de DSE, no período de janeiro/2003 a dezembro/2004, quando foram dosados BNP e Creatinina (Cr) séricos, e realizado ecocardiograma transtorácico (ECO). Os pacientes foram estratificados em 2 grupos (G1 e G2) de acordo com o valor de Cr: G1, com Cr menor ou igual a 1,2mg por cento, e G2 com Cr maior que 1,2mg por cento e maior ou igual a 2,0mg por cento. A performance no diagnóstico de IC medida pela área sobre a curva ROC (ACROC) foi comparada entre os dois grupos...

Importância dos níveis do fator natriurético tipo B e de marcadores inflamatórios em pacientes com cardiomiopatia isquêmica submetidos à revascularização miocárdica cirúrgica: correlação com a evolução e prognóstico imediato / The importance of B-type natriuretic peptide and inflammatory markers levels in patients with ischemic cardiomiopathy undergoing cardiac surgery: correlation with immediate outcome

Foram avaliados níveis de fator natriurético tipo B (BNP) e marcadores inflamatórios em 62 pacientes com e sem cardiomiopatia isquêmica submetidos à revascularização miocárdica com circulação extracorpórea. No pré-operatório, verificou-se diferença entre o grupo com e sem disfunção para níveis de BNP e molécula de adesão intercelular 1 (ICAM-1). Na amostra geral, BNP pré-operatório apresentou correlação com tempo de terapia intensiva (UTI), ventilação mecânica e uso de dobutamina. BNP pré-operatório foi preditor de internação em UTI > 5 dias e uso de dobutamina / Preoperative levels were different between the group with cardiac dysfunction and the group without for BNP (207,5  201,5 pg/ml vs.30,2  67,1 pg/ml; p<0,001) and sICAM (146,6  62,1 ng/ml vs. 119,2  48,8 ng/ml; p<0,04). In the whole sample, preoperative BNP levels correlate with longer intensive care unit stay (p=0,029), longer ventilator use (p=0,018) and duration of dobutamine use (p=<0,001). Receiver operating characteristic curve demonstrated BNP levels as predictor of intensive care unit stay > 5 days and dobutamine use, with areas under the curve of 0,832 e 0,842, respectively. Preoperative levels of sICAM were associated with inhospital mortality (p=0,042). In the postoperative period, was found association between PCR (p=0,013), IL-6 (p=0,006) e P-selectin (p=0,001) with ventilation duration and P-selectin (p=0,009) intensive care unit stay...

Avaliação de pacientes assintomáticos com formas cardíacas iniciais da doença de Chagas, através da análise de eletrocardiograma dinâmico, ecocardiograma e peptídeo natriurético tipo B / Evaluation of asymptomatic patients with initial cardiac forms of Chagas' disease, through the analysis of dynaminc electrocardiogram and type B natriuretic peptides

Para avaliar as características clínicas e evolutivas em pacientes com formas cardíacas iniciais assintomáticas da doença de Chagas, realizou-se estudo prospectivo em 108 pacientes com idade entre 18 e 50 anos, atendidos entre abril e novembro de 2002 no ambulatório de doença de Chagas da Universidade Estadual de Londrina. Os pacientes foram submetidos a 1)avaliação clínica, 2)eletrocardiograma (ECG), 3)radiografia de tórax e cálculo do índice cardio-torácico (ICT), 4)eletrocardiografia dinâmica de 24 horas, 5)ecocardiografia bidimensional com Doppler tecidual e 6)dosagem plasmática do peptídeo natriurético tipo B (BNP). Os pacientes foram divididos em 3 grupos: 50 no GI – ECG e ICT normais, 31 no GIIA – ECG com alterações características de doença de Chagas e 25 no GIIB – ECG com alterações não características de doença de Chagas. /To evaluate clinical and evolutive features in patients with initial asymptomatic cardiac Chagas’ disease, a prospective study was carried out with 108 patients, age 18 and 50, at the Londrina State University Chagas’ disease outpatient clinic, from April to November 2002. Patients were submitted to: 1) clinical evaluation, 2) electrocardiography (EKG), 3) chest radiography and cardiothoracic index (CTI), 4)24-hour dynamic electrocardiography, 5) bi-dimensional echocardiography with tissued Doppler imaging and 6) type-B natriuretic peptide (BNP) plasmatic dosage. Patients were divided into 3 groups: GI - normal EKG and CTI (50 patients), GIIA - EKG with typical Chagas’ disease alterations (31 patients) and GIIB - EKG with alterations not characteristic of Chagas´ disease (25 patients)...