Un novedoso agente en el tratamiento de la insuficiencia cardiaca con función sistólica deprimida / A novel agent in the treatment of heart failure with depressed systolic function

Resumen Introducción: Se revisará la evolución del tratamiento farmacológico de la insuficiencia cardiaca (IC) en los últimos 25 an˜os, desde el concepto de tratamiento con vasodilatadores, pasando por el bloqueo o inhibición del sistema renina-angiotensina-aldosterona y la inhibición betaadrenérgica y su importante contribución en la disminución de la morbimortalidad por IC, el papel de los péptidos natriuréticos y, finalmente, se conocerá uno de los estudios más importantes en el área cardiológica y específicamente en el manejo de la IC, en el cual se demuestra un enfoque modulador de los sistemas neuro humorales que se activan en estos pacientes. Objetivos: La IC constituye la etapa final de la mayoría de las enfermedades cardiovasculares, con una alta tasa de hospitalización y de morbimortalidad cardiovascular, siendo, por lo tanto, de interés constante la necesidad de encontrar un agente terapéutico innovador que disminuya significativamente estas complicaciones y también que mejore la calidad de vida de los que la presentan. Metodología: Se realizará una descripción del PARADIGM-HF Clinical Trial, que utilizó un compuesto sacubitrilo/valsartán para el manejo de la IC con un mecanismo modulador diferente del concepto de bloqueador de sistemas deletéreos que se activan cuando un paciente presenta síntomas y signos de IC. Conclusiones: La muerte por causas cardiovasculares u hospitalización por IC (el punto final primario) se produjo en 914 pacientes (21.8%) en el grupo sacubitrilo/valsartán y 1,117 pacientes (26.5%) en el grupo de enalapril (razón de riesgo en el grupo sacubitrilo/valsartán, 0.80; intervalo de confianza (IC) del 95%: 0.73 a 0.87; p < 0.001 (exacta p = 4.0 × 10 - 7)). De los pacientes que recibieron sacubitrilo/valsartán, 537 (12.8%) fueron hospitalizados por IC, en comparación con los 658 pacientes (15.6%) que recibieron enalapril (razón de riesgo, 0.79; IC del 95%, 0.71 a 0.89; p < 0.001). Un total de 711 pacientes (17.0%) en el grupo sacubitrilo/valsartán y 835 pacientes (19.8%) en el grupo de enalapril murió (razón de riesgo de muerte por cualquier causa, 0.84; IC del 95%, 0.76 a la 0.93; p < 0.001).

Abstract Introduction: A review is presented on the evolution of the pharmacological treatment of heart failure (HF) in the last 25 years, from the concept of treatment with vasodilators to the blocking or inhibition of the renin angiotensin aldosterone system. Beta-adrenergic inhibition and its important contribution in the reduction of morbidity and mortality due to HF will be discussed along with the role of the natriuretic peptides. One of the most important studies in the cardiology area, and specifically in the management of HF, is presented, in which an approach is demonstrated of the modulator of the neurohumoral systems that are activated in these patients. Objectives: HF is the final stage of most cardiovascular diseases, and has a high rate of hospital admission, as well as cardiovascular morbidity and mortality. Therefore, there is constant interest in the need to find an innovative therapeutic agent that significantly reduces these complications and that improves the quality of life of those who suffer from it. Methods: A description will be presented of the PARADIGM-HF Clinical Trial using a sacubitril/valsartán compound for the management of HF with a modulating mechanism different from the concept of a deleterious system blocker that is activated when a patient has symptoms and signs of heart failure. Conclusions: Death due to cardiovascular causes, or hospital admission due to heart failure (the primary endpoint) occurred in 914 patients (21.8%) in the Sacubitril / valsartán group, and 1117 patients (26.5%) in the enalapril group (risk ratio in the sacubitril / valsartán group, 0.80, with a 95% confidence interval [CI]: 0.73 to 0.87, P<0.001 ;exact P= 4.0 × 10 --7;). Of the patients receiving sacubitril / valsartán, 537 (12.8%) were hospitalised due to heart failure, compared with 658 patients (15.6%) receiving enalapril (hazard ratio 0.79, 95% CI: 0.71 to 0.89, P<.001). A total of 711 patients (17.0%) in the sacubitril / valsartán group, and 835 patients (19.8%) in the enalapril group, died (all-cause death rate, 0.84, 95% CI: 0.76 to 0.93, P<.001)

Value of hypoxia-inducible factor 1α in diagnosis and prognosis of acute decompensated chronic heart failure / 上海交通大学学报（医学版）

Objective·To investigate the value of hypoxia-inducible factor 1α (HIF-1α) in diagnosis and prognosis of acute decompensated chronic heart failure (CHF).Methods·32 patients with acute decompensated CHF (Group A),33 patients with stable CHF (Group B) and 30 controls (Group C) were included.HIF-1α,B-type natriuretic peptide (BNP) and other biochemical indicators in blood were detected.Length of stay and readmission frequency within 3 months of Group A were recorded.Correlations between HIF-1α and other indicators were analyzed.ROC curves of HIF-1α and BNP were developed to compare their diagnostic values.Results·The HIF-1α and BNP levels of Group A were both significantly higher than those of Group B and Group C (P＜0.05).HIF-1α was positively correlated with serum creatinine,hemoglobin,BNP,length of stay and readmission frequency within 3 months (P＜0.05).Areas under curves of HIF-1α and BNP showed no statistically difference (P＞0.05).Conclusion·HIF-1 α has a certain value in diagnosis and prognosis of acute decompensated CHF.

Value of hypoxia-inducible factor 1α in diagnosis and prognosis of acute decompensated chronic heart failure / 上海交通大学学报（医学版）

Objective: To investigate the value of hypoxia-inducible factor 1α (HIF-1α) in diagnosis and prognosis of acute decompensated chronic heart failure (CHF). Methods: 32 patients with acute decompensated CHF (Group A), 33 patients with stable CHF (Group B) and 30 controls (Group C) were included. HIF-1α, B-type natriuretic peptide (BNP) and other biochemical indicators in blood were detected. Length of stay and readmission frequency within 3 months of Group A were recorded. Correlations between HIF-1α and other indicators were analyzed. ROC curves of HIF-1α and BNP were developed to compare their diagnostic values. Results: The HIF-1α and BNP levels of Group A were both significantly higher than those of Group B and Group C (P0.05). Conclusion: HIF-1α has a certain value in diagnosis and prognosis of acute decompensated CHF.

The value of left ventricular Tei Index in evaluating the cardiac function and prognosis of patients with sepsis-induced cardiomyopathy / 中华急诊医学杂志

Objective To determine whether left ventricular Tei Index evaluate the cardiac function and prognosis of patients with sepsis-induced cardiomyopathy (SIC).Methods A total of 86 patients with septic shock combined with SIC in the emergency department of Beijing Chaoyang Hospital affiliated to Capital Medical University from July 2014 to June 2016 were recruited and divided into non-survival group (n=35) and survival group (n=51) according to 28-day follow-up.Left ventricular Tei Index, BNP, cTNI and left ventricular ejection fraction within the first 24 h after admisson were detected and compared between the two groups.The correlations of left ventricular Tei Index to BNP, cTNI and ejection fraction were analyzed.The receiver operating characteristic curves (ROC) were constructed to analysize the value of Tei Index in evaluating the cardiac function and prognosis.Results The patientsin the non-survival group had a higher Tei Index compared with that in the survival group [(0.75±0.13) vs.(0.51±0.09), P<0.05].The Tei Index of SIC patients was significantly positively correlated with BNP and cTNI (both P<0.05), and significantly negatively correlated with ejection fraction (P<0.05).The AUC of Tei Index for predicting 28-day mortality in SIC patients was high comapred with that of BNP, cTNI and ejection fraction.Conclusion The left ventricular Tei Index has a reliable value in evaluating the cardiac function and prognosis of patients with SIC.

The influence on B-type natriuretic peptide, cardiac troponin Ⅰ and D-dimer after intervention in CX3CL1 of acute pulmonary embolism by curcumin / 中国中西医结合急救杂志

Objective To observe the effects of curcumin on B-type natriuretic peptide (BNP),cardiac troponin Ⅰ (cTnI) and D-dimer in rats with acute pulmonary embolism (APE).Methods The irregular cbemotactic factor (CX3CL1)-shRNA and overexpression vector were designed and synthesized,and adenovirus packages were respectively carried out.Sixty Spargue-Dawley (SD) rats were divided into normal control group,sham-operation group,model group,curcumin group,curcumin+CX3CL1-shRNA group and curcumin+CX3CL1 overexpression vector group by random number table (each group 10 rats).The APE rat models were duplicated by autologous blood embolus method.in the pharmacological intervention groups,1 day and again 40 minutes before operation,a dose of curcumin 100 mg/kg was administered by gavage respectively;in virus intervention groups,3 days before modeling,intravenous injection of 109 pfu into a tail vein was performed once;in sham-operation group and model group,an equivalent dose of normal saline 2 mL daily was administered by gavage;the normal group did not accept any intervention.Six hours after modeling,the change of lung tissue were observed under confocal laser scanning microscope,the lung tissue was taken for hematoxylin-eosin (HE) staining,histopathological changes of lung tissue were observed,and the levels of serum BNP,cTnI,D-dimer were detected by enzyme-linked immunosorbent assay (ELISA).Results Virus infected lung tissue was green,nucler was blue.The HE staining in lung tissue showed:histopathological changes in the model group were more obvious than those in normal group and sham-operation group,after curcumin intervention,some emboli in pulmonary arteries in all treatment groups were partially dissolved,and the inflammation was alleviated.The results of ELISA shows:the contents of cTnI,BNP,D-dimer were significantly higher in model group than those in shamoperation group [cTnI (ng/L):224.97 ± 37.96 vs.149.13 ± 36.65,BNP (ng/L):53.66 ± 21.72 vs.24.62 ± 10.44,D-dimer (ng/L):78.68 ± 13.10 vs.42.00 ± 9.30,all P ＜ 0.05];the contents of cTnI,BNP,D-dimer were significantly lower in curcumin group,curcumin+shRNA group and curcumin+CX3CL1 overexpression vector group than those in model group (cTnI was 162.98 ± 28.65,143.32 ± 34.55,159.50 ± 37.80 vs.204.97 ± 37.96,all P ＜ 0.05,BNP was 27.45 ± 11.00,26.95 ± 6.66,33.05 ± 7.05 vs.53.66 ± 21.72,all P ＜ 0.05,D-dimer was 54.34 ± 4.57,53.38 ± 11.01,56.33 ± 6.80 vs.78.68 ± 13.10,all P ＜ 0.05);there were no statistical significant differences in comparisons among all intervention groups (all P ＞ 0.05).Conclusion Curcumin is able to improve serum BNP,cTnI,D-dimer in APE rats,but its relation with CX3CL1 is not obvious.

The effects of serum C-reactive protein, B-natriuretic peptide and cholinesterase on prognosis in elderly patients with pulmonary infection / 中国中西医结合急救杂志

Objective To investigate the effects of levels of serum C-reactive protein (CRP), B-natriuretic peptide (BNP) and cholinesterase (ChE) on prognosis of elderly patients with pulmonary infection.Methods Sixty cases aged ≥ 65 years old with lung infection admitted to Departments of Infectious Diseases and Respiration of Hebei Provincial People's Hospital from March 2012 to March 2014 were enrolled. According to the diagnostic criteria of pulmonary infection and the severity score (PSI) of pneumonia, the patients were classified into three groups with different grades of infectious severity (PSI Ⅰ-Ⅲ, PSI Ⅳ, PSI Ⅴ groups), 20 cases in each group; in the same period, 20 elderly healthy people having accepted the physical examination in this hospital were designed as the healthy control group. Furthermore, according to the difference in prognosis, the patients were divided into a survival group (52 cases) and a death group (8 cases). The PSI scores, the levels of white blood cell count (WBC), D-Dimer, CRP, BNP and ChE, mortalities, times of stay in hospital were compared between the PSI Ⅰ-Ⅲ, PSI Ⅳ, PSI Ⅴ groups and the healthy control group as well as between the survival and death groups.Results The periods of stay in hospital of patients with PSI Ⅳ and Ⅴ were much longer than that patients with PSI Ⅰ-Ⅲ (days: 14.7±2.1, 18.3±2.6 vs. 9.2±1.7, both P 0.05). Compared with the survival group, the PSI score, the levels of WBC, D-dimer, CRP and BNP after treatment in death group were markedly higher [PSI score: 141.5±23.3 vs. 97.6±18.2; WBC (×109/L): 15.9±1.9 vs. 12.1±1.8; D-Dimer (μg/L): 1 373.9±179.4 vs. 627.4±69.6; CRP (mg/L): 69.8±9.8 vs. 42.6±7.3; BNP (ng/L): 2 745.6±374.9 vs. 1 022.2±171.3; allP < 0.05], the level of ChE was significantly lower (U/L: 2 569±309 vs. 5 692±777,P < 0.05).Conclusion The serum levels of CRP, BNP and ChE in aged patients with pulmonary infection are helpful to the early diagnosis of disease severity, so as they have guiding significance in predicting prognosis.

Curative effect of levosimendan on treatment of patients with refractory heart failure / 中国基层医药

Objective To evaluate clinical curative effect of levosimendan therapy on patients with refractory heart failure.Methods A total of 84 patients with refractory heart failure were randomly and equally divided into le-vosimendan group and routine treatment group.Both groups received routine antiheart failure medication,levosimendan group received levosimendan therapy while routine treatment received milrinone injection therapy additionally.Changes of left ventricular ejection fraction(LVEF)and plasma level of N terminal pro type B natriuretic peptide(NT -proB-NP)were compared between two groups before and after treatment.Results Compared with routine treatment group, there were significant increase in total effective rate of LVEF[(0.36 ±0.18)% vs.(0.42 ±0.36)%],and in NT -proBNP[(975.14 ±247.01)ng/mL vs.(832.14 ±224.78)ng/mL].The effect before and after treatment of levosi-mendan group were more obviously (NT -proBNP:t =2.3 -230.2,P <0.02;LVEF:t =2.29 -215.2,P <0.01). Conclusion Levosimendan can significantly improve heart function,decrease NT -proBNP level in patients with re-fractory heart failure.

The Association Between Left Ventricular Hypertrophy and Biomarkers in Patients on Continuous Ambulatory Peritoneal Dialysis

BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) is a major cardiovascular complication and an important predictor of mortality in patients with end stage renal disease. Some studies have shown that the serum aldosterone levels are correlated with LVH in non-diabetic patients undergoing hemodialysis. The objective of this study was to elucidate the relationships between serum biomarkers, including aldosterone, and echocardiographic findings, such as LVH, in patients on peritoneal dialysis. SUBJECTS AND METHODS: Thirty patients on continuous ambulatory peritoneal dialysis (CAPD) for >12 months at Soonchunhyang University Cheonan Hospital were included. Transthoracic echocardiography was performed and the left ventricular mass index (LVMI) was calculated using the Devereux formula. Serum biomarkers {N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T, C-reactive protein, renin, and aldosterone} were measured. RESULTS: Sixteen of 30 patients had LVH on the basis of the LVMI. The mean serum aldosterone level was 62.53+/-60.73 pg/mL (range, 5.03-250.68 pg/mL). LVH, on the basis of the LVMI, was not correlated with the serum aldosterone level. The serum aldosterone levels were not associated with echocardiographic findings, even with co-existing diabetes mellitus. The LVMI had a negative correlation with the hemoglobin (r=-0.405, p=0.029) and hematocrit (r=-0.374, p=0.042), and a positive correlation with NT-proBNP (r=0.560, p=0.002). The other biomarkers (renin, aldosterone, troponin T, and C-reactive protein) were not correlated with the LVMI. The LVMI was correlated with the left atrium volume index (r=0.675, p<0.001). CONCLUSION: NT-proBNP is a good marker to predict LVH in patients undergoing CAPD. The serum aldosterone level is not correlated with LVMI, even with co-existing diabetes mellitus.