Plasma BNP Research Articles

Effect of seven steps rehabilitation exercise on the exercise tolerance and life quality of chronic heart failure patients

Objective To explore the effect of seven steps rehabilitation exercise on the exercise tolerance and life quality of chronic heart failure patients.Methods Totals of 60 chronic heart failure patients randomly divided into experimental group (n =30) and control group (n =30).On the basic of conventional drug therapy and nursing,the experimental group carried out seven steps rehabilitative exercise,while control group received routine nursing.And the two groups of patients' left ventricular ejection fraction (LVEF),plasma BNP,blood lactate and 6 min walking distance and life quality (MHL score) were separately checked at the beginning and at the time after 16 weeks of exercise.Results These two groups of patients' LVEF,plasma BNP levels,blood lactate,6 min walking distance and their quality of life showed no significant difference at the beginning (P ＞0.05).Compared with the control group,after 16 weeks' movements,the experimental group' s LVEF increased obviously (44.52 ± 4.5)％,plasma BNP level decreased (402.6 ± 112.4) ng/L,blood lactate decreased (4.97 ± 0.50)mmol/L,6 min walking distance increased (482.52 ± 50.34)m and life quality increased (39.3 ± 10.8),the differences were statistically significant (t =2.21,3.32,2.41,5.05,7.52,respectively ;P ＜ 0.05).Before and after the intervention,patients' LVEF,plasma BNP levels,blood lactate,6 min walking distance and their quality of life in control group showed no significant difference at the beginning (P ＞ 0.05).Conclusions Seven steps rehabilitative exercise can significantly increase chronic heart failure patients' exercise tolerance,and improve their life quality. Key words: Chronic heartfailure; Seven steps movement; Exercise tolerance ; Quality of life

Abstract 3: Vascular Smooth Muscle ADAM17 is Critical for End-organ Damage but not Hypertension Induced by Angiotensin II Infusion in Mice

A metalloprotease, ADAM17, mediates EGF receptor (EGFR) activation in vascular smooth muscle cells (VSMC) by angiotensin II (Ang II) leading to hypertrophy. dnADAM17 prevents vascular neointimal hyperplasia. To test if vascular ADAM17 silencing has any therapeutic potential against hypertension, we evaluated Ang II-induced end-organ damage as well as hypertension in ADAM17 flox/flox mice bred with sm22α Cre mice (Cre+/-). Upon Ang II infusion (1 μg/kg/min) for 2 weeks, control Cre-/- mice showed phenotypes of cardiac hypertrophy; HW/BW ratio (mg/g: 12.1±1.6 vs 6.2±0.4 p<0.05 n=8), cardiac echo (LVPWd mm: 0.96±0.05 vs 0.75±0.04, p<0.05) and plasma BNP (pg/mL: 1.94±0.36 vs 0.07±0.2, p<0.05) compared with saline infusion. Histological assessments demonstrated medial hypertrophy and perivascular fibrosis of coronary arteries with Ang II infusion. In contrast, these phenotypic changes were attenuated in VSMC ADAM17 silenced Cre+/- hearts with Ang II infusion; HW/BW ratio (7.0±0.8 vs 6.6±0.7 n=5), cardiac echo (LVPWd: 0.71±0.09 vs 0.65±0.09) and BNP (0.52±0.19 vs 0.03±0.003, p<0.05) compared with saline infusion. Control Cre-/- with Ang II infusion also demonstrated renal dysfunction assessed by BUN (mg/dL: 40.1±2.9 vs 23.0±2.8 p<0.05 n=6) compared with saline infusion, which was partially prevented in Cre+/- mice (30.4±2.5 vs 21.3±4.0 p<0.05). Renal fibrosis observed in Cre-/- with Ang II infusion was also attenuated in Cre+/- with Ang II infusion. However, Ang II induced hypertension in both Cre-/- and +/- mice assessed by radiotelemetry (MAP mmHg: 160±6 vs 155±7). Ang II infusion in Cre-/- enhanced ADAM17 and phospho-Tyr1068 EGFR staining in vasculatures of heart and kidney, whereas Ang II infused Cre+/- had diminished phospho-Tyr1068 EGFR staining and no ADAM17 staining in the vasculatures. qPCR analyses of cardiac ADAM17 mRNA in hearts further support these findings. In addition, IHC analyses revealed less oxidative stress and less ER stress in heart and kidney of Ang II-infused Cre-/- compared with Ang II-infused Cre+/-. These data suggest that vascular ADAM17/EGFR axis is critical for end organ damage via induction of ER/oxidative stress independent from blood pressure regulation.

Chronic uninephrectomy in a large animal is characterized by preservation of cardiovascular homeostasis but with cardiorenal activation of the cGMP system together with atrial fibrosis

Purpose: While renal donation is safe and widely employed for the treatment of endstage chronic kidney disease, recent experimental and human studies suggest complex cardiovascular adaptation that may impact long-term cardiovascular homeostasis. Indeed, in a large animal model of acute uninephrectomy (UNX) we observed reduced CO and increased SVR. Here we define chronic cardiovascular, renal and humoral adaptation in a large animal model 12 weeks after UNX with the goal of understanding integrative adaptations so as to advance possible cardiorenal protective strategies in the setting of mild renal insufficiency and UNX commonly associated with renal donation. Methods: Dogs were assigned to UNX (n=6) or sham operation (n=6). Echocardiography was performed at baseline and after 12 weeks. At 12 weeks cardiovascular, renal and humoral functions were assessed invasively. Fibrosis was assessed by Picrosirius red staining, and microarray analyses were performed on tissue from the left atrium (LA) and left ventricle (LV). Data are presented as mean±SD, * indicates p<0.05. Results: UNX dogs had compensatory increased left kidney (LK) weight at 12 weeks (80±10 vs. 59±5g, *) as well as increased LK GFR (59±11 vs. 41±6 mL/min, *). The groups were equal regarding MAP, PAP, PCWP, CO and SVR, and diastolic and systolic functions were unaltered in both groups 12 weeks after surgery. Plasma ANP, BNP and aldosterone were not different after 12 weeks, however plasma cGMP was higher in the UNX dogs (6.2±1.2 vs. 4.6±1.0 pmol/mL, *). LK urinary cGMP excretion was increased in the UNX dogs (1132±325 vs. 667±121 pmol/min, *) and there was a trend for increased renal generation of cGMP (UNX 777±345 vs. sham 475±112 pmol/min, p=0.07). Left atrial fibrosis was higher in the UNX group (13.7±5.1 vs. 7.7±2.3%, *). The UNX group had > 2 fold significant changes in the expression of 10 genes in the LA and 7 genes in the LV, associated with cardiac remodeling. Conclusion: UNX in a large animal is characterized by compensatory renal hypertrophy and preserved cardiovascular homeostasis after 12 weeks. Importantly however, the cardiorenal protective cGMP system is activated which may reflect triggering of endogenous vasodilating pathways mediating the preserved cardiovascular and renal function. Furthermore, our model is characterized by subclinical atrial fibrosis and altered remodeling-related gene expressions in the LA and LV. These studies provide insights into the complex responses to UNX and possible cGMP therapeutic strategies for cardioprotection in the setting of reduced renal mass.

Inter-atrial dyssynchrony contributes to heart failure symptoms in patients with preserved ejection fraction: a potential novel therapeutic target

Introduction: The pathophysiology of heart failure with preserved ejection fraction (HFPEF) remains poorly understood and the potential contribution of atrial function to the development of symptoms has been scarcely investigated. The aim of our study was to assess the role of inter-atrial dyssynchrony (IAD), a potentially treatable condition, as a mechanism involved in the development of heart failure symptoms. Methods: 56 subjects investigated for new onset of heart failure symptoms were included: 29 with HFPEF criteria and 27 subjects matched by age, gender, risk factors and without heart failure criteria according to the ESC guidelines. In all subjects a transthoracic echocardiography was performed and plasma BNP levels were measured. The time from p wave onset on the ECG to peak negative strain (atrial contraction) was determined using speckle tracking from apical 4 chamber views; the time difference between both atria (ms) was used as an index of IAD. T-student, Pearson correlation and ROC curves were used. Results: Mean age was 73±8 years (71% female),78% with hypertension. HFPEF patients showed an increased IAD as compared to subjects without HFPEF (76±32 vs 28±7 ms, p 60 ms showed increased BNP values as compared with IAD < 60 ms (145±130 vs 48±38 pg/mL, p<0.01). A significant correlation between BNP levels and IAD was found (figure). ![Figure][1] Conclusion: HFPEF patients showed an increased IAD; the extent of IAD is related to BNP levels and the diastolic pattern. IAD could be an important mechanism involved in the development of symptomatic HFPEF and a potential target for device therapy. [1]: pending:yes

Prognostic significance of tricuspid valve regurgitation in patients with autely decompensated heart failure

Background: Tricuspid regurgitation (TR) caused by right ventricular pressure and/or volume overload frequently remains in patients with acutely decompensated heart failure (ADHF) after successful treatment. However, it is unclear whether TR provides a prognostic significance in those patients. Methods and results: Of 757 consecutive patients admitted with ADHF, 558 patients, who had available echocardiograhic data at discharge, were studied. Patients were followed up to a mean period of 861 days. The influence of TR on cardiovascular events was analyzed. TR severity was graded to 1, none-mild; 2, moderate; 3, severe; visually based on 2D color-flow imaging. TR flow velocity was measured using continuous-wave Doppler in acquirable cases. During the follow-up period, 138 patients (24.7%) underwent adverse cardiovascular event including death or hospital readmission for heart failure. Echocardiographic assessment of patients at discharge revealed higher TR severity (1.7±0.8 vs. 1.4±0.6, p<0.001) and greater flow velocity (2.8±0.6 vs. 2.6±0.5 m/s, p=0.003) in the event group. Multivariate Cox proportional hazards regression analysis showed TR severity is an independent predictor of cardiovascular event (p=0.04) among variables including serum Na concentration, plasma BNP level, age, and prior heart failure. Kaplan-Meier survival curves demonstrated that TR flow velocity ≥3m/s (p=0.02) and higher TR severity (p=0.004) are associated with poor clinical outcome in ADHF patients (Figure). ![Figure][1] Figure 1 Conclusion: Severity of right ventricular pressure and volume overload are the predictors of adverse cardiovascular outcome in patients discharged after ADHF. [1]: pending:yes

Left ventricular outflow tract velocity time integral correlates with low cardiac output syndrome in patients with acute decompensated heart failure

Purpose: Left ventricular outflow tract velocity time integral (LVOT VTI) is a simple method by Doppler echocardiography to calculate left ventricular stroke volume. In ESC guidelines, LVOT VTI<15cm is defined as an abnormality suggesting reduced left ventricular stroke volume, however it is unknown whether it correlates with low cardiac output syndrome (LOS) or not. The aim of this study is to elucidate the usefulness of LVOT VTI when diagnosing LOS and to decide the optimal cut-off value for inotrope administration in acute decompensated heart failure (ADHF). Methods: A total of 212 patients admitted for ADHF were divided into two groups according to LVOT VTI. Clinical characteristics were compared between High-VTI (VTI≥15cm, n=99) and Low-VTI (VTI<15cm, n=113). Results: Low-VTI showed younger age (p=0.0001), lower systolic blood pressure (p=0.005), faster HR (p=0.0004), higher plasma BNP levels (p=0.0134), lower %FS (16.1 vs. 23.6%, p<0.0001), compared with High-VTI. Low-VTI showed higher prevalence of inotrope administration (37.2 vs. 14.1%, p=0.0002) and LOS signs, such as pulsus alternans (17.7 vs. 8.1%, p=0.0006), cool extremities (26.6 vs. 9.1%, p=0.0012) and proportional pulse pressure<25% (17.7 vs. 8.1%, p=0.0436). There was no difference in in-hospital and 3-year mortality between two groups. In ROC curve analysis, the optimal cut-off value of LVOT VTI for prediction of LOS signs and inotrope administration were 13.9cm (sensitivity 0.68; specificity 0.69; AUC 0.72) and 12.3cm (sensitivity 0.68; specificity 0.81; AUC 0.76), respectively. ![Figure][1] Conclusions: Low-VTI was associated with the presence of LOS signs and requirement of inotrope administration in patients with ADHF, suggesting importance of LVOT VTI measurements to assess LOS in ADHF. [1]: pending:yes

Acute heart failure volume control trial: the comparison of tolvaptan and carperitide

Background: Acute decompensated heart failure (ADHF) is a common and highly morbid cardiovascular disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of prognosis of ADHF patients. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide. Methods and results: One hundred and nine hospitalized ADHF patients were enrolled and randomly assigned tolvaptan or carperitide treatment groups. We compared the efficacy and safety of these two drugs. Subjective symptoms and plasma BNP level were similarly improved by treatment in both groups. Blood pressure was significantly lower in the carperitide group than in the tolvaptan group after treatment (P<0.05). Urine volume was significantly higher in the tolvaptan group (P<0.01), but volume of water intake was also higher in the tolvaptan group (P<0.01). Adverse cardiac events such as worsening heart failure and hypotension requiring drug discontinuation were more frequent in the carperitide group (P=0.027). The average drug cost of tolvaptan was significantly lower than that of carperitide (P<0.001). ![Figure][1] Conclusions: The present study reveals that tolvaptan is a novel promising agent for ADHF in terms of efficacy, safety, and economy compared to carperitide. [1]: pending:yes

GW24-e3975 Plasma brain natriuretic peptide lever between dynamic blood pressure and left ventricular hypertrophy in elderly hyperension

ObjectivesTo study the relationship between parameters of 24 hour dynamic blood pressure (BP) and plasma brain natriuretic peptide and left ventricular hypertrophy in elderly Hyperension patients.MethodsAmbulatory BP monitoring (ABPM) for...

What have genome-wide association studies taught us about cGMP and blood pressure regulation?

Background Hypertension (HTN) is a major worldwide cause of stroke, heart failure, myocardial infarction, and chronic kidney disease. Mechanisms of blood pressure regulation have previously been elucidated from the study of animal models, Mendelian hyper- and hypo-tension in humans, and drug treatment trials. More recently, genome-wide association studies (GWASs) have offered unbiased approaches to identify novel mechanisms contributing to blood pressure control. We and others have reported candidate gene and GWASs that have identified common genetic variants of modest effect on blood pressure that fall in pathways involving natriuretic peptide and nitric oxide signalling [1-3]. Results Common variant rs5068 in the 3’ UTR of NPPA ,w hich encodes the atrial natriuretic peptide (ANP), is associated with higher plasma ANP and lower blood pressure and odds of hypertension [2]. We have now completed a genotype-directed physiologic study of 8 heterozygotes and 23 major homozygotes demonstrating that the variant alters the “set point” of ANP (p=0.02) but does not alter the ANP response to high vs low sodium diet (p<0.0001) or to intravenous saline infusion (p<0.0001, in press); additional evidence for the mechanism by which this variant acts will be presented in a separate abstract. Downstream of the natriuretic peptide system, a common noncoding variant at a locus including NPR3, encoding the natriuretic peptide clearance receptor, has been associated with blood pressure although it is not associated with plasma ANP or BNP [3]. A common variant at the locus including ENOS, encoding endothelial nitric oxide synthase, is associated with blood pressure and hypertension [4,5]. Lastly, an intronic variant in GUCY1A3, encoding the alpha subunit of soluble guanylate cyclase, is associated with blood pressure and myocardial infarction risk. Conclusion The natriuretic peptide and nitric oxide systems are important contributors to blood pressure regulation in humans and represent strong targets for pharmacologic intervention to reduce the burden of disease from hypertension.

The effects of super-flux (high performance) dialyzer on the plasma glycosylated pro-B-type natriuretic peptide (proBNP) and glycosylated N-terminal proBNP in end-stage renal disease patients on dialysis

Background: Plasma BNP levels are predictive of prognosis in hemodialysis patients. However, recent studies showed that the current BNP immunoassay cross-reacts with glycosylated proBNP, and the NT-proBNP assay underestimates glycosylated NT-proBNP. In addition, the recently developed high performance dialyzer removes medium-sized molecular solutes such as b2-microgloburin. We therefore investigated the effects of high performance dialysis on measured levels of glycosylated proBNP, glycosylated NT-proBNP and other BNP-related peptides in end-stage renal disease (ESRD) patients on hemodialysis. Method: The relationships between clinical parameters and BNP-related molecule were also investigated. We used our newly developed immunoassay to measure plasma total BNP and proBNP in 105 normal subjects and 36 ESRD patients before and after hemodialysis. Plasma NT-proBNP was measured using Elecsys II after treatment with or without deglycosylating enzymes. We also measured plasma ANP and cGMP using radioimmunoassays. Results: All the measured BNP-related peptides were significantly higher in ESRD patients than healthy subjects. Total BNP (238.9%), proBNP (229.7%), glycoNT-proBNP (245.5%), nonglycoNT-proBNP (253.4%), ANP (250.4%) and cGMP (272.1%) were all significantly reduced after hemodialysis, and the magnitude of the reduction appeared molecular weightdependent. Both the proBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios were increased after hemodialysis. The former correlated positively with hemodialysis vintage and negatively with systolic blood pressure, while the latter correlated positively with parathyroid hormone levels. Conclusion: These results suggest that hemodialysis using super-flux dialyzer removes BNP-related peptides in a nearly molecular weight-dependent manner. The ProBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios appear to be influenced by hemodialysis-related parameters in ESRD patients on hemodialysis.

Adaptive servo‐ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure

This study investigated whether abnormal cardiac sympathetic nerve activity (SNA) is associated with the severity of central sleep apnoea (CSA) and whether adaptive servo-ventilation (ASV) therapy can improve cardiac SNA in heart failure (HF) patients with predominant CSA. Overnight polysomnography was conducted to diagnose CSA. Cardiac SNA was analysed by [123I]metaiodobenzylguanidine scintigraphy in 26 consecutive HF patients with predominant CSA. Of the 26 patients, 10 agreed to ASV therapy. Cardiac SNA was analysed 6 months after initiating ASV based on a non-randomized protocol. The apnoea-hypopnoea index and central apnoea index were significantly correlated with the washout rate (WR) and a delayed heart to mediastinal (H/M) ratio, suggesting that SNA is associated with abnormal breathing patterns. The WR, H/M ratio, plasma BNP level, and LVEF were significantly improved (WR, 40.0 ± 11.6% vs. 34.6 ± 11.4%, P = 0.046; H/M ratio, 1.5 ± 0.1 vs.1.8 ± 0.3, P = 0.013; ln BNP, 5.4 ± 1.0 vs. 4.6 ± 1.2, P = 0.007; and LVEF, 43.8 ± 10.4% vs. 47.0 ± 10.6%, P < 0.001) in the ASV group patients, but not in the non-ASV group patients. Multiple linear regression analyses showed that a decreased WR was strongly associated with an increased LVEF (coefficient = -0.454, P = 0.013). Abnormal cardiac SNA could be significantly correlated with the severity of CSA in HF patients. ASV therapy might improve cardiac function in these patients by partially mediating cardiac SNA regulation.

臨床 本態性高血圧症における血漿ANP,BNP濃度測定の意義

臨床 本態性高血圧症における血漿ANP,BNP濃度測定の意義

Rapid progression to pulmonary arterial hypertension crisis associated with mixed connective tissue disease in an 11-year-old girl

Mixed connective tissue disease (MCTD) is rare in pediatric rheumatic diseases. Pulmonary arterial hypertension (PAH) associated with MCTD usually progresses gradually and is difficult to note at the asymptomatic phase. We report a 11-year-old girl with MCTD complicated with rapidly progressive PAH. Although PAH was not detected by echocardiogram or chest CT scan at the initial examination, it became clear in 1 year and suddenly came to cardiac arrest during an invasive procedure. She was successfully treated with extracorporeal assist and both vasodilative and immunosuppressive medication. A combination of echocardiogram and plasma BNP levels could be a useful marker for the follow-up of such cases. PAH could develop early in the course of pediatric MCTD and needs attention to unexpected acute exacerbation, especially under emotional stress.

The therapeutic effect of enteral nutrition support on chronic cardiac failure of rats

Objective To study the therapeutic effect and mechanism of enteral nutrition support for treatment of chronic cardiac failure of rats.Methods Ligature of abdominal aorta was used to prepare SD rat model of chronic cardiac failure.The rat models of cardiac failure were randomly (random number) divided into three groups:conventional therapy group,conventional therapy plus enteral nutrition support group and non-therapy group.The rats in conventional therapy group were administrated with routinely used drugs for chronic cardiac failure.The rats in conventional therapy plus enteral nutrition support group were treated with conventionally used medicine plus enteral nutrition liquid.The rats in non-therapy group were given the same amounts of dummy medicine and normal saline.Ultrasonic cardiography,ELISA for detection of atrial natriuretic peptide (BNP) and examination of pathological change in myocardium tissues after HE staining were carried out for comparison of cardiac function of rats with chronic heart failure between pre-and post-treatment.Results The commonly used drug enabled the heart of rats with chronic heart failure to elevate the LVFS (left ventricular fraction shortening) and LVEF (left ventricular ejection fraction) levels (q=3.59,P＜0.05; q=4.01,P＜0.05),to decrease the BNP in blood plasma (u=2.285,P＜0.05) and to lessen the injury of myocardial tissue (u =2.332,P ＜ 0.05).However,compare to the chronic cardiac failure rats administrated with commonly used drug,the chronic cardiac failure rats treated by combination of the commonly used drug and enteral nutrition liquid presented significantly higher LVFS and LVEF levels (q =4.34,P ＜ 0.05 ; q =3.98,P ＜ 0.05),lower plasma BNP level (u =2.548,P ＜0.02) and milder injury of myocardial tissue (u=2.631,P＜0.02).Conclusions The commonly used drug plus enteral nutrition support promotes in higher efficiency the heart function of chronic cardiac failure rats,suggesting that this nutrition support can be used as an adjuvant therapy for patients with chronic cardiac failure in clinic. Key words: Chronic cardiac failure; Enteral nutritional supportive therapy; Rats; Brain natriuretic peptide ; Ventricular function; Ultrasonic cardiogram; HE staining; Curative effect

Treatment of Diabetes in People with Heart Failure

Treatment of Diabetes in People with Heart Failure

A simple score for predicting paroxysmal atrial fibrillation in acute ischemic stroke

Background and purposeOur aim in this study was to investigate factors associated with paroxysmal atrial fibrillation (PAF) in acute stroke patients and to develop a risk score to predict the presence of PAF. MethodsWe retrospectively enrolled patients with acute ischemic stroke within 24h of onset between June 2006 and April 2008. Patients with sustained AF were excluded. Patients were divided into two groups according to the presence of PAF: the PAF group or the non-PAF group. The clinical factors associated with PAF were investigated. Furthermore, we devised a new risk score to predict the presence of PAF. ResultsThere were 215 patients enrolled. The PAF group had 32 (14.9%) patients. Multivariate logistic regression analysis demonstrated that NIHSS score≥8 (OR, 4.2; 1.38–12.88), left atrial size≥3.8cm (OR, 4.8; 1.65–13.66), mitral valvular disease (OR, 7.5; 2.17–25.90), and plasma BNP level≥144pg/ml (OR, 12.8; 4.12–40.00) were independent factors associated with PAF. We developed a risk score from these variables (total score 0 to 5): NIHSS score≥8 (1 point); left atrial size≥3.8cm (1 point); mitral valvular disease (1 point); and BNP level≥144pg/ml (2 points). The frequency of PAF was 0% with a score of 0, 4% with a score of 1, 14% with a score of 2, 26% with a score of 3, 50% with a score of 4 and 100% with a score of 5 ConclusionOur simple score can predict the presence of PAF during hospitalization in acute ischemic stroke.

Effect of omega-3 on brain natriuretic peptide and echocardiographic findings in heart failure: Double-blind placebo-controlled randomized trial

BackgroundPossible beneficial effects of dietary omega-3 supplementation on patients with congestive heart failure (CHF) were investigated. Methods and results100 patients with CHF who had a tri-chamber pacemaker and automated defibrillator were initially recruited, and 70 agreed to participate.38 patients received 2 g/day of omega-3 and 32 received placebo capsules. BNP level, 6-min walk test and echocardiographic parameters were recorded at baseline and after 6 months of treatment.BNP levels decreased significantly after 6 months in the omega-3 group, from 1766.2 ± 1978.1 pg/mL to 1159.4 ± 1430.9 pg/dL (P < 0.005). Tei index and late diastolic velocity index were significantly improved in treated group. Mortality and hospitalization rates did not differ. ConclusionThe beneficial effects of omega-3 supplementation in patients with CHF were not as clear as hypothesized; however, omega-3 fatty acids can result in small changes in plasma BNP levels and modest improvements in echocardiographically assessed diastolic function (Clinical trial.gov registration: NCT01227837).

The Beneficial Impact of Fasudil and Sildenafil on Monocrotaline-Induced Pulmonary Hypertension in Rats: A Hemodynamic and Biochemical Study

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.

Abstract TP302: Brain Natriuretic Peptide Upon Admission Should Predict Patients Mortality Within 1 Year After Onset Of Intracerebral Hemorrhage

Background and Purpose: A recent study demonstrated that the plasma level of BNP is an independent predictor of long-term mortality after ischemic stroke. Furthermore, BNP also increases in patients with acute intracerebral hemorrhage (ICH). However, the relationship between BNP and long-term mortality after ICH is not clear. We investigated the relationship between BNP and mortality within 1 year after onset of ICH. Methods: We prospectively enrolled ICH patients who were admitted within 24 hours of onset from April 2007 to December 2010 and measured plasma BNP upon admission. Follow up was performed at 12 month from enrollment and patients were divided into two groups: the survival group and the death group. The factors associated with mortality were determined by multiple logistic regression analysis. Results: A total of 304 patients ( median age, 72 years , 112 female) were enrolled in the present study. The locations of the hematoma were: the putamen in 102 (34%)patients, the thalamus in 93 (30%), the lobar in 40 (13%), the brainstem in 28 (9%), the cerebellum in 20 (7%), and other location in 21 (7%). 86 patients (28%) died during 12 month from enrollment. The mean±SD admission BNP level for all patients was 123.1±320.8 pg/ml. The median of age, NIHSS score on admission, frequency of preadmission warfarin use, preadmission antiplatelet use, a past history of diabetes mellitus, atrial fibrillation, ICH, coronary artery disease, hemoglobin, glucose level, ICH volume and BNP level were significantly higher in the death group than in the survival group. In multivariate logistic regression analysis, age &gt;71years (odds ratio [OR], 2.3; 95%CI, 1.080-5.054, P =0.03112), NIHSS score on admission &gt;16 (OR, 2.9; 95%CI, 1.407-6.053, P =0.00400), past history of diabetes mellitus (OR, 2.5; 95%CI, 1.139-5.567, P =0.02246), glucose level &gt;145 mg/dl (OR, 2.0; 95%CI, 1.005-4.136, P =0.04831), ICH volume &gt;10 cc (OR, 4.1; 95%CI, 1.963-8.503, P =0.00017), and a plasma BNP level &gt;50 pg/ml (OR, 2.9; 95%CI, 1.457-5.931, P =0.00260) were found to be independently associated with mortality within 1 year after onset. Conclusions: BNP level (&gt;50 pg/ml) upon admission should predict patients mortality within 1 year after onset of ICH.

Minimal dose for effective clinical outcome and predictive factors for responsiveness to carvedilol: Japanese chronic heart failure (J-CHF) study

BackgroundIn chronic heart failure (CHF), it remains unclear whether the minimal dose of beta-blockade is related to survival benefits and which parameter predicts morbidity and mortality. We sought to determine the minimal dose related to survival benefits by comparing the efficacy and safety of three doses of carvedilol and the best predictive parameter for effective outcomes in Japanese patients with CHF. MethodsIn this prospective, randomized, stratified trial, 364 patients with mild to moderate CHF were assigned to a daily carvedilol dose of 2.5, 5, or 20mg, plus optimal standard therapy. FindingsDuring the mean 3-year follow-up, resting heart rate (HR) and BNP were significantly reduced with dose–response relations in the early period but without dose–response relations in the late period. The LVEF and the LVDd were increased and decreased, respectively, without a dose–response relation. No significant difference was seen in the composite primary endpoint of all-cause mortality and hospitalization for cardiovascular diseases and heart failure. Multivariate analysis indicated early decreases in HR and BNP predicted long-term outcomes. However, adverse events increased dose-dependently. Among 237 polymorphisms in 87 heart failure-related genes, the osteopontin G-156 del genotype was associated with an event-free survival rate (Wilcoxon test, P=0.030). ConclusionsA low carvedilol dose is effective if the HR and/or plasma BNP has been reduced. Carvedilol therapy should be guided by reductions in HR and/or BNP, especially by initial HR reduction, but not only by its dose. OPN might be a surrogate genetic marker for long-term event-free survival.