Plasma Brain Natriuretic Peptide Levels Research Articles

Detection of Pediatric Pulmonary Arterial Hypertension by School Electrocardiography Mass Screening.

Rationale: To detect pulmonary arterial hypertension (PAH) at any early stage is a promising approach to optimize the outcome. Objectives: To investigate the impact of school ECG-based screening on detecting idiopathic or heritable (I/H)-PAH in the general pediatric population. Methods: This was a nationwide survey of patients with I/H-PAH newly diagnosed at 3 months to 18 years of age in Japan during 2005-2012. Measurements and Main Results: Eighty-seven eligible patients (age range, 1-16 yr) were recruited. Among 68 (78%) patients diagnosed at greater than or equal to 6 years of age (the age of the first ECG-based screening), 28 (41%) were detected by the ECG-based screening (screening group) and 40 (59%) were recognized by their symptoms (n = 37) or coincidental occasions (n = 3; nonscreening group). In the screening group, the proportion of patients in World Health Organization functional class I/II at diagnosis was higher (96% vs. 60%; P < 0.001), plasma brain natriuretic peptide level was lower (149 ± 290 vs. 398 ± 559 pg/ml; P = 0.045), and 6-minute-walk distance was longer (420 ± 109 vs. 327 ± 104 m; P < 0.001) than the nonscreening group, despite similar values in mean pulmonary artery pressure (58 ± 17 vs. 61 ± 17 mm Hg; P = 0.42) and pulmonary vascular resistance index (18 ± 8 vs. 21 ± 11 Wood units ⋅ m2; P = 0.24) between groups. The proportion of patients on intravenous epoprostenol at the final visit was lower in the screening group than the nonscreening group (14% vs. 50; P = 0.004). Conclusions: These findings suggest that the ECG-based screening detects a unique subpopulation of pediatric patients with I/H-PAH that is associated with already established pulmonary hypertension but without obvious right heart failure and warrants investigating the prognostic significance of this system.

Increased Plasma Soluble Fractalkine in Patients with Chronic Heart Failure and Its Clinical Significance

Fractalkine has been reported to play an important role in the pathophysiology of various cardiovascular disorders. This research aims to study the change of soluble fractalkine (sFKN) in plasma level of patients with chronic heart failure (CHF) and evaluate its prognostic value.A total of 96 patients with CHF and 45 healthy subjects were included in this study. The plasma levels of sFKN, brain natriuretic peptide (BNP), and Interleukin-18 (IL-18) were determined by ELISA kits when they were first admitted to the hospital. Left ventricular ejection fraction (LVEF) was measured by echocardiogram. Rehospitalization status within 1 year after the first hospitalization was also recorded.The plasma levels of sFKN, BNP, and IL-18 in patients with CHF were significantly higher than in the control group (P < 0.05). The concentrations of sFKN and BNP were increased with the severity of heart failure classified by NYHA classification (P < 0.05). There were no statistical differences among all CHF subgroups classified by etiology (P > 0.05). Plasma sFKN level in CHF group was positively correlated with BNP (r = 0.441, P < 0.001) and IL-18 (r = 0.592, P < 0.001). Receiver operating characteristic curve analysis showed that area under the curve values of FKN, BNP, and IL-18 were 0.885 (95%CI: 0.810 to 0.960, P < 0.001), 0.889 (95%CI: 0.842 to 0.956, P < 0.001), and 0.878 (95%CI: 0.801-0.954, P < 0.001), respectively. The concentrations of sFKN and BNP were increased in patients readmitted more than once within 1 year (P < 0.05).

Heart Failure With Midrange Ejection Fraction in Patients Admitted for Acute Decompensation: A Report from the Japanese Multicenter Registry

Patients having heart failure with midrange ejection fraction (HFmrEF: 40% ≤ EF < 50%) are increasingly being considered a new subset of the population with heart failure. Despite recent advances in heart-failure treatment strategies, the prognosis of these patients has not improved substantially over time. In addition, the significance of this new phenotype in hospitalized patients with acute decompensated heart failure (ADHF), another population whose prognosis has not improved, also remains poorly understood. This study aimed to describe the clinical characteristics, prognosis and treatment responses of patients with HFmrEF hospitalized for ADHF. On the basis of consecutive inpatient data from a multicenter ADHF registry, 651 of 3572 patients (17.1%) were classified as having HFmrEF. Prognostic factors predicting composite outcomes, defined as all-cause death and heart failure readmission, as well as all-cause death alone, were analyzed. In the median follow-up duration of 724 days, both composite endpoints and all-cause death alone were comparable in those with heart failure with preserved ejection fraction, HFmrEF and heart failure with reduced ejection fraction. Age, anemia, hyponatremia, elevated blood urea nitrogen, chronic kidney disease, and elevated plasma brain natriuretic peptide levels were significant predictors of composite outcomes in HFmrEF. Roughly one-sixth of the patients with ADHF had HFmrEF. The long-term prognosis of patients with HFmrEF was not significantly different from that of patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction in the population with ADHF. Risk factors for adverse outcomes in HFmrEF were also similar to those for heart failure with preserved ejection fraction and HFmrEF in the hospitalized population with ADHF.

Cardioprotective effect of the secretome of Sca-1+ and Sca-1− cells in heart failure: not equal, but equally important?

Both progenitor and differentiated cells were previously shown to secrete cardioprotective substances, but so far there has been no direct comparison of the paracrine effects of the two cell types on heart failure. The study sought to compare the paracrine effect of selected progenitors and the corresponding non-progenitor mononuclear cardiac cells on the cardiac function of transgenic heart failure mice. In addition, we aimed to further enhance the paracrine effect of the cells via pretreatment with the heart failure mediator aldosterone. Transgenic heart failure mice were injected with the supernatant of murine cardiac stem cell antigen-1 positive (Sca-1+) and negative (Sca-1-) cells with or without aldosterone pretreatment. Cardiac function was determined using small animal magnetic resonance imaging. In addition, heart failure markers were determined using enzyme-linked immunosorbent assay, RT-PCR, and bead-based multiplexing assay. While only the secretome of aldosterone pretreated Sca-1+ cells led to a significant improvement in cardiac function, N-terminal pro brain natriuretic peptide plasma levels were significantly lower and galectin-1 levels significantly higher in mice that were treated with either kind of secretome compared with untreated controls. In this first direct comparison of the paracrine effects of progenitor cells and a heterogeneous population of mononuclear cardiac cells the supernatants of both cell types showed cardioprotective properties which might be of great relevance for endogenous repair. During heart failure raised aldosterone levels might further increase the paracrine effect of progenitor cells.

May 2019 at a glance: epidemiology, drug effects on biomarkers, adverse events with LVAD.

May 2019 at a glance: epidemiology, drug effects on biomarkers, adverse events with LVAD.

Correlations of Changes in Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) with Levels of C-Reactive Protein (CRP) and TNF-α in Pediatric Patients with Sepsis.

BackgroundThis study investigated the changes in plasma brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels in pediatric patients with sepsis, and explored their relationships with serum inflammatory factors in pediatric patients.Material/MethodsA total of 120 pediatric patients with sepsis admitted to and treated at our hospital from 2013 to 2017 were divided into 4 groups: a systemic inflammatory response syndrome (SIRS) group (n=28), a sepsis group (n=35), a severe sepsis group (n=27), and a septic shock group (n=30). Plasma BNP, cTnI, and creatine kinase-MB (CK-MB) levels in pediatric patients in the 4 groups were measured, and the correlations of BNP and cTnI with plasma inflammatory factors C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were investigated.ResultsThe plasma BNP and cTnI levels in pediatric patients with sepsis were significantly higher than those in the SIRS group (p<0.05). After hospitalization and treatment, levels of BNP and cTnI in pediatric patients were decreased. The concentrations of BNP and cTnI were correlated with CRP level (r=0.88 and 0.88, respectively). The associations (r value) of BNP and cTnI with TNF-α levels were 0.35 and 0.48, respectively.ConclusionsThe levels of plasma BNP and cTnI are associated with the severity of sepsis in pediatric patients, and were positively correlated with CRP and TNF-α levels, which provides a novel strategy for the early diagnosis and evaluation of sepsis in pediatric patients.

Brain natriuretic peptide in pregnant women with heart disease

Plasma brain natriuretic peptide levels were prospectively studied in pregnant women with heart disease. Fifty pregnant women with heart disease and 25 controls were evaluated at 24 weeks or under, 30-32 weeks, 34 weeks or more of gestation, and 6 weeks postpartum. Adverse maternal cardiac events were hospitalization for worsening heart failure, stroke, and death. Thirty-eight (76%) women had rheumatic heart disease. Plasma brain natriuretic peptide levels were (in cases and controls) 118.3 ± 46.5 pg/ml and 66.3 ± 15.9 pg/ml (at 24 weeks or under), 124.8 ± 30.4 pg/ml and 68.4 ± 16.5 pg/ml (30-32 weeks), 135.8 ± 34.9 pg/ml and 68.6 ± 15.6 pg/ml (34 weeks or more), and 110.1 ± 21.9 pg/ml and 65.0 ± 16.1 pg/ml (6 weeks postpartum) (p = .0001). Eighteen women had adverse events. Of these, only 1 had a level less than 100 pg/ml, 12 were between 100 and 200 pg/ml, and 5 more than 200 pg/ml. Plasma brain natriuretic peptide levels were higher in women with heart disease at all periods of gestation as well as six weeks postpartum. No woman with a plasma brain natriuretic peptide levels of 98 pg/ml or less had an adverse event.

Empagliflozin Ameliorating Effect of on Plasma Triglyceride: An Association with Endothelial Function Recovery in Diabetic Patients with Coronary Artery Disease

Introduction: The mechanisms behind the cardiovascular benefits of Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have not been fully clarified. We aimed to identify potential mechanisms underlying the favorable effects of SGLT2 inhibitors on cardiovascular events. Methods: The 50 diabetic patients with established Coronary Artery Disease (CAD) included in this study analysis were administered 10 mg/day of empagliflozin. Cookie meal testing (carbohydrates: 75 g, fat: 28.5 g), endothelial function testing using Flow-Mediated Dilatation (FMD), and body composition evaluation were performed before and after 6 months treatments. Evaluation of changes in % FMD between treatment periods, and its association with metabolic biomarkers were evaluated. Results: After the 6 month treatment, body weight and body fat percentage decreased significantly, while body muscle percentage increased significantly. HbA1C level and fasting and postprandial plasma glucose levels were significantly decreased by treatment. Postprandial insulin secretion was also significantly suppressed and insulin resistance index was significantly decreased. Furthermore, fasting and postprandial triglyceride levels decreased significantly while total ketone body increased significantly after the 6 months treatment. While plasma brain natriuretic peptide level was not changed, C-reactive protein was decreased, and FMD was significantly improved after the 6 months treatment. Multiple regression analysis showed the strongest predictive factor of FMD improvement to be change in fasting and postprandial plasma triglyceride levels. Conclusion: SGLT2 inhibitors improved multiple metabolic parameters. Of these, reduction in plasma triglyceride was strongly associated with endothelial function recovery in diabetic patients with CAD, and this reduction may be related to the cardiovascular benefit of SGLT2 inhibitors.

BRAIN NATRIURETIC PEPTIDE (BNP) AS A BIOMARKER OF CARDIAC TOXICITY IN CASES OF ACUTE CARBON MONOXIDE POISONING

Background: Acute carbon monoxide (CO) poisoning is a common toxicity emergency that leads in many occasions to morbidity and mortality. Acute myocardial injury is commonly observed among acute carbon monoxide poisoned patients and cardiac toxicity is found to be the cause of mortality in the majority of cases. Some studies recorded normal values of cardiac troponins in cases of acute CO poisoning with cardiac affection. Hence it is important to search for novel and sensitive biomarkers to diagnose cardiac ischemia in these cases. Brain natriuretic peptide (BNP) is a cardiac hormone which is produced mainly in the ventricular myocardium in response to myocardial hypoxia. Aim: The present study aims to investigate the value of BNP measurement in detection of cardiac toxicity in acute carbon monoxide poisoning. Methods: The present study was conducted on 42 patients with acute CO poisoning admitted to the Poison Control Centre of Ain Shams University hospitals (PCC-ASUH). Routine laboratory tests and ECG were done on admission in addition to determination of the level of BNP and determination of troponin I. Results: Analysis of the results showed that there is an increase in the levels of BNP in patients suffering from acute CO poisoning with high levels seen in those with ischemic changes recorded by ECG. Conclusions: The present study concluded that plasma BNP levels could be used as a specific reliable biomarker of cardiac toxicity in patients with acute CO poisoning.

Oltipraz attenuates the progression of heart failure in rats through inhibiting oxidative stress and inflammatory response.

To evaluate the effect of oltipraz (OPZ) on isoproterenol-induced heart failure (HF) and heart function. We also explore the underlying molecular mechanism of OPZ. The rats were randomly divided into four groups, including normal control group, isoproterenol (ISO) group, ISO +100 mg/kg OPZ group, and OPZ group. Hemodynamic parameters, such as left-ventricular systolic pressure, were statistically analyzed. Besides, plasma levels of brain natriuretic peptide (BNP), pro-inflammatory cytokines and antioxidant markers were assessed by using enzyme-linked immunosorbent assay (ELISA). Moreover, histopathological examination was applied to assess the degree of cardiac interstitial fibrosis. OPZ could statistically improve the hemodynamic parameters of the heart function, and could also obviously attenuate cardiac interstitial fibrosis in ISO-induced HF rats when compared with the ISO group. Besides, plasma level of BNP in ISO +100 mg/kg OPZ group dramatically decreased in comparison with that of ISO group. Moreover, compared with ISO group, OPZ treatment significantly reduced the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, OPZ treatment remarkably increased the levels of antioxidant markers such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) in ISO-induced HF rats. OPZ administration may provide experimental evidence for the possible effect of OPZ on isoproterenol-induced heart failure in rats. Moreover, OPZ administration may have potential utility for the treatment of heart failure.

Chronic vagal nerve stimulation exerts additional beneficial effects on the beta-blocker-treated failing heart.

Vagal nerve stimulation (VNS) induces bradycardia in chronic heart failure (CHF). We hypothesized that beta-blocker would cover the beneficial effects of VNS on CHF if the anti-beta-adrenergic effect was the main VNS effect. This study investigated the effects of VNS on cardiac remodeling in rats with CHF treated with metoprolol. Two weeks after myocardial infarction, surviving rats were randomly assigned to groups of sham stimulation (SS), sham stimulation with metoprolol (SSM), or VNS with metoprolol (VSM). Compared to the SS group, heart rate was significantly reduced in the SSM and VSM groups. Hemodynamic assessments showed that VSM rats maintained better cardiac pump function and presented higher cardiac index and lower heart weight than SSM rats. VSM was also associated with lower plasma brain natriuretic peptide and norepinephrine levels than SSM. VSM but not SSM improved the 50-day survival rate compared with the SS group. The results suggest that VNS may exert its beneficial effects on the failing heart independently of its anti-beta-adrenergic mechanism.

Association of brain natriuretic peptide and adrenomedullin plasma levels with left ventricular filling pressures in end-stage renal disease patients on hemodialysis.

Adrenomedullin (ADM) and brain natriuretic peptide (BNP) are known to be associated with elevated left ventricular filling pressures. However, little is known about this association in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF). Our objective was to evaluate the potential association between E/e' ratio and plasma levels of BNP and ADM in end-stage renal disease (ESRD) patients with preserved LVEF undergoing chronic hemodialysis. The study group enrolled 62 ESRD patients treated with hemodialysis three times weekly. BNP and ADM plasma concentration measurements and echocardiographic examination were performed 30 minutes after hemodialysis. E/e' ratio, evaluated by Tissue Doppler imaging and measured at the basal septum, was used as a surrogate marker for assessing left ventricular filling pressures. The mean age of patients was 62 ± 25 years. The mean BNP and ADM values after hemodialysis were 0.40 ± 6.73 ng/ml and 0.06 ± 2.12 ng/ml, respectively. Elderly patients with hypertrophied left ventricles and larger left atria displayed higher E/e' values. BNP (r = 0.324. p = 0.018) and ADM (r = 0.319, p = 0.042) plasma levels were positively and significantly associated with E/e΄. Multivariate regression analysis including BNP, ADM, age, hemodialysis duration, left ventricular end-systolic volume index, LVEF, left ventricular mass index and left atrium volume index, revealed that ADM (p-value 0.025) but not BNP levels, were independently associated with the E/e' ratio. ADM, but not BNP, was independently associated with septal E/e' in HD patients with preserved LVEF. ADM plasma levels can be used as a surrogate index to assess left ventricular filling pressures in HD patients.

Effect of human umbilical cord mesenchymal stem cells by intramuscular injection on cardiac function and microvascular regeneration in rats with dilated cardiomyopathy

Objective To evaluate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) treatment through intramuscular administration on the heart function and angiogenesis of the myocardium in dilated car-diomyopathy (DCM) rats induced by Adriamycin(ADR). Methods One hundred male SD rats were randomly divided into the normal group and the DCM group.Rats in the DCM group were treated with ADR by intraperitoneal injection of 2.0 mg/kg dose per week for 8 weeks in order to induce DCM.Sixty modeled surviving rats with DCM were randomly divided equally into 3 groups, and they were treated with hUCMSCs or DMEM by intramuscular injection.Rats in the DMEM group (20 cases) received intramuscular infusion 2 mL DMEM alone; rats in the low-dose group (20 cases) underwent intramuscular infusion of 1×106 hUCMSCs/2 mL in DMEM; rats in the high dose group (20 cases) underwent intramuscular infusion of 10×106 hUCMSCs/2 mL in DMEM.Echocardiography and plasma brain natriuretic peptide(BNP) were used to assess cardiac function in modeled rats.The morphological changes in myocardial cells were observed by using HE and Masson staining after ADR injection stopped for one week.Four weeks after administration of hUCMSCs, echocardiography was performed to evaluate the cardiac function, and plasma BNP level was detected by enzyme immunoassay kit.Western blot was used to analyze the expression of vascular endothelial growth factor(VEGF) in myocardium of rats in each group.Myocardial microvessel density was detected by using anti-CD34 monoclonal antibody and transmission electron microscopy (TEM) were performed to observe the ultrastructure of microvessel. Results Left ventricular ejection (LVEF) and left ventricular fractional shortening (LVFS) in the DCM groups[( 66.17±3.54)%, (31.33±3.20)%] were significantly decreased compared to those in the normal group[(77.25±3.40)%, (41.00±2.94)%], and the differences were statistically significant(t=10.620, 10.328, all P<0.05); the morphological changes in myocardial cells was observed by using HE and Masson staining.Pit-induced typical histological lesion of myocardial tissue was observed in the DCM group, such as congestion, edema, a disorganization of myocytes and focal necrosis and myocardial tissue with wispy, broad collagen fibers predominating in the matrix.Four weeks after administration of hUCMSCs, LVEF in the low dose group or the high dose group were significantly higher compared with those in the DMEM group[(72.27±2.44)% or (70.92±2.68)% vs.(62.89±2.54) %], and the differences were statistically significant( t=2.145, 2.131, all P<0.05); and LVFS were significantly higher compared with that in the DMEM group [(34.96±2.08)% or (33.49±2.19)% vs.(30.98±2.22)%], and the differences were statistically significant (t=2.491, 4.086, all P<0.05). The plasma level of BNP was significantly declined in the hUCMSCs treated rats as compared to those before treatment[ low dose group (352.68±41.25) ng/L vs. (202.68±20.38) ng/L, t=2.052, P<0.05; high dose group (355.79±48.32) ng/L vs. (193.62±15.41) ng/L, t=2.074, P<0.05]. Quantitative analysis demonstrated that microvessel density was significantly hi-gher in low-dose and high-dose hUCMSCs treated DCM rats than that in the DMEM treated DCM rats [(84.00±19.18)/mm2 or (86.67±20.88) /mm2vs.(27.14±13.97) /mm2, t=2.109, 2.101, all P<0.05]; Western blot test showed that there had high expression of VEGF in myocardium and TEM in the high dose group, and vessel injury in DMEM treated rats were more serious than that of hUCMSCs treated rats. Conclusion It suggests that hUCMSCs intramuscular injection may improve heart function and angiogenesis of myocardium in DCM rats induced by adriamycin. Key words: Dilated cardiomyopathy; Cardiac function; Angiogenesis; Stem cell therapy; Intramuscular injection; Rat

Plasma brain natriuretic peptide is a biomarker for screening ischemic cerebral small vessel disease in patients with hypertension.

Plasma brain natriuretic peptide (BNP), a diagnostic marker of cardiovascular diseases, has been previously linked to cerebrovascular diseases. Our goal was to determine whether plasma BNP level is helpful for identifying high-risk individuals who are likely to present with the 3 main subtypes of cerebral small vessel diseases (CSVDs), namely, white matter lesions, lacunar infarcts, and cerebral microbleeds, on magnetic resonance imaging (MRI) in patients with hypertension.Three hundred forty-six consecutive hypertensive patients presenting at our cardiology or neurology clinic were investigated. Plasma BNP level was measured by chemiluminescent microparticle immunoassay. The presence of CSVD was assessed by 1.5-T brain MRI. Multivariate linear regression was used to determine whether individual or combined MRI-defined CSVD subtypes were associated with BNP level, after adjustment for several covariates.The mean age of patients was 69.1 ± 9.8 years, and 44.2% were female. The highest quartile BNP group was positively associated with advanced age, female sex, clinically manifesting cardiac diseases, and ischemic CSVD (white matter lesions and lacunar infarcts) and no association with cerebral microbleeds. According to multivariate linear regression, white matter lesions [β = 0.722; 95% confidence interval (95% CI), 0.624–0.819] and lacunar infarcts (β = 0.635; 95% CI, 0.508–0.762) were independently associated with BNP level, even after controlling for vascular risk factors and clinically manifesting cardiac diseases. Combined white matter lesions and lacunar infarcts were more strongly associated with BNP level than each subtype alone. With the cutoff value of 106.4 pg/mL, BNP level had a sensitivity, a specificity, and an area under the curve of 95.2%, 64.9%, and 0.799, respectively, for white matter lesions, whereas the values were 143.0 pg/mL, 81.6%, 73.5%, and 0.848, respectively, for lacunar infarcts.Plasma BNP level, which is independently correlated with individual or combined white matter lesions and lacunar infarcts, is a useful molecular marker for identifying ischemic CSVD in patients with hypertension.

Positive pediatric exercise capacity trajectory predicts better adult Fontan physiology rationale for early establishment of exercise habits

ObjectiveExercise training is recommended for its possible favorable effects on Fontan pathophysiology. This study aimed to elucidate the impact of pediatric exercise capacity trajectory, which may mimic the effect of exercise training, on late adult Fontan pathophysiology. MethodsSince 1990, 97 Fontan patients had consecutively undergone two serial cardiopulmonary exercise tests (CPX1 and CPX2) during childhood (ages 8 ± 2 and 14 ± 2 years) and one during adulthood (CPX3; age 23 ± 5 years). The changes in peak oxygen uptake (PVO2: % of normal value) from CPX1 to CPX2 (1-dPVO2) and from CPX2 to CPX3 (2-dPVO2) were calculated, and then the patients were divided into four subgroups according the 1-dPVO2 and 2-dPVO2. ResultsIn their adulthood, when compared with groups with negative 1-dPVO2, the central venous pressure, plasma brain natriuretic peptide level, and renal resistive index were lower, whereas liver synthetic function, body fat-free percentage, and PVO2 were higher in those with positive 1-dPVO2 (p < 0.05–0.0001). However, these favorable associations of 2-d-PVO2 with adult Fontan pathophysiology were not observed, except for the PVO2. After CPX3, 13 unexpected events occurred, and the risk was 76% lower in the groups having positive 1-dPVO2 than in those with negative 1-dPVO2 (hazard ratio, 0.24; 95% confidence interval, 0.09–0.62; p = 0.0035). ConclusionsA positive exercise capacity trajectory during childhood predicts better adult Fontan pathophysiology, including better prognosis. Thus, prescription of exercise could be a promising strategy in the management of pediatric Fontan patients.

The effects of xanthine oxidase inhibitor in patients with chronic heart failure complicated with hyperuricemia: a prospective randomized controlled clinical trial of topiroxostat vs allopurinol\u2014study protocol

BackgroundHyperuricemia has a close relationship with cardiovascular diseases including heart failure. However, it is controversial whether xanthine oxidase inhibition has benefits for patients with chronic heart failure. We designed the Effect of Xanthine Oxidase Inhibitor in Chronic Heart Failure Patients Complicated with Hyperuricemia study (Excited-UA study) to compare the beneficial effects between a novel xanthine oxidoreductase inhibitor, topiroxostat, and a conventional agent, allopurinol, in patients with chronic heart failure and hyperuricemia. We focus on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiography-based cardiac function, vascular endothelial function, renal function, inflammation, and oxidative stress.MethodsThe excited-UA is a prospective, randomized, open-label, blinded-endpoint clinical trial designed to prove our hypothesis that topiroxostat is more effective than allopurinol in patients with chronic heart failure and hyperuricemia. A total of 140 patients with chronic heart failure and hyperuricemia (plasma brain natriuretic peptide level ≥ 40 pg/mL and serum uric acid level ≥ 7.0 mg/dL) are randomly assigned (ratio 1:1) into either the topiroxostat group (40–160 mg/day) or allopurinol group (100–300 mg/day), to achieve the target uric acid level of 6.0 mg/dL. According to the protocol, all patients are followed up annually for 24 weeks. The primary endpoint is percent change in serum NT-proBNP level at 24 weeks from baseline.ConclusionsThe Excited-UA study would provide novel evidence for the clinical relevancy of xanthine oxidoreductase inhibitor treatment in patients with chronic heart failure and hyperuricemia.

Ubiquinone Plasma Levels are Correlated with Brain Natriuretic Peptide Plasma Levels in Patients with Chronic Heart Failure: The Potential of Coenzyme Q10 Combined Therapy

Abstract Despite the association of a worse HF-related clinical status with lower CoQ10 levels, the prognostic use of CoQ10 is controversial. The aim of this study is to optimize pharmacotherapy for patients with ischaemic CHF, based on the clinical and functional parameters of the heart and brain natriuretic peptide (BNP) plasma levels, which are correlated with the CoQ10 plasma levels, and to assess patient prognosis after receiving CoQ10 therapy. This prospective clinical study included 75 patients aged 56 to 63 years old with coronary heart disease (CHD) classified as class I–III according to the NYHA classification. After assessment of the clinical-instrumental characteristics of the CVD course (complaints, medical history, physical examination, a 6-minute walk test, echocardiography, and test for reactive hyperaemia), we determined the BNP level and CoQ10 plasma levels. At the same time, we assessed the efficacy of CoQ10 treatment (at a dose of 60 mg/per day) and tolerability in CVD-combined therapy during a follow-up of 12 weeks. CoQ10 supplementation in HF patients induced improvements in their functional cardiac parameters, such as the ejection fraction. Our results suggest that supplemental CoQ10 may be a useful option for effective management of heart failure and warrant future adequately powered randomized controlled trials of CoQ10 supplementation in patients with HF.

Effect of renal sympathetic denervation on ventricular and neural remodeling.

BackgroundThis study assessed the therapeutic effects of renal sympathetic denervation (RDN) on post-myocardial infarction (MI) ventricular remodeling and sympathetic neural remodeling in dogs. The possible mechanisms and optimal time for treatment are discussed.MethodsWe randomly assigned 30 dogs to five groups: RDN 1 week before MI (RDN1w + MI; n = 6), RDN 1 week after MI (MI1w + RDN; n = 6), RDN 2 weeks after MI (MI2w + RDN; n = 6), control (N; n = 6), and MI (n = 6). A canine model of myocardial infarction was established by interventional occlusion with a gelatin sponge via the femoral artery. Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) levels were measured and echocardiography was performed to assess cardiac function and heart size. All dogs were killed at the end of the experiment and samples of cardiac and renal arteries were obtained. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 in cardiac and of tyrosine hydroxylase (TH) in renal arteries was assessed by immunohistochemistry. Sympathetic innervations in the infarction border zone were investigated via Western blotting and real-time PCR.ResultsLeft ventricular function in the MI group decreased significantly, while plasma BNP and ET-1 levels as well as MMP-2 and MMP-9 expression increased. Compared with the MI group, the RD groups showed significantly reduced MMP‑2, MMP‑9, TH, and growth-associated protein (GAP) 43 expression in the RDN1w + MI, MI1w + RDN, and MI2w + RDN groups was significantly improved. Additionally, the expression of TH in renal arteries decreased after RDN.ConclusionRDN has preventive and therapeutic effects on post-MI ventricular remodeling and sympathetic neural remodeling. The mechanism of RDN is likely mediated through restraint of renal sympathetic nerve activity.

Prevalence and clinical characteristics of obstructive- and central-dominant sleep apnea in candidates of catheter ablation for atrial fibrillation in Japan

IntroductionWe aimed to study the prevalence and types of sleep apnea (SA) as well as their clinical characteristics in atrial fibrillation (AF) ablation candidates in Japan. MethodsBefore catheter ablation, 197 consecutive AF patients (age: 60 ± 9 years, body mass index; 25.0 ± 3.0) were evaluated with portable polygraphy. We compared the clinical characteristics, according to the severity of SA as well as its types, as defined by the presence of obstruction and the mixed vs. central apnea indices. ResultsThe mean apnea–hypopnea index (AHI) was 17.7 ± 11.9, with 135 AF patients having an AHI ≥10 (68.5%). Patients with an AHI ≥10 had a significantly higher body mass index, plasma brain natriuretic peptide (BNP) level, prevalence of hypertension, and larger left atrial size. Among patients with an AHI ≥10, the incidence of obstructive-dominant SA was 60.9% and that of central-dominant SA was 7.6%. The prevalence of hypertension was significantly higher in obstructive-dominant SA patients (obstructive vs. central: 48.3% vs. 20.0%, P = 0.038). The obstructive apnea index correlated with plasma BNP level and age, but the central and mixed apnea indices did not. ConclusionsThe prevalence of SA was common in AF ablation candidates, even without an obesity epidemic, and the SA type was predominantly obstructive. Portable polygraphy was useful for detecting undiagnosed SA patients in AF ablation candidates.

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early‐ and late‐onset pre‐eclampsia

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P< 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P< 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.