Brain Natriuretic Peptide Concentrations Research Articles

1407Drug effect of luseogliflozin and voglibose on heart failure with preserved ejection fraction in diabetic patients: a multicenter randomized-controlled trial

Abstract Background Recent randomized, placebo-controlled trial in patients with type 2 diabetes demonstrated that the sodium-glucose cotransporter 2 inhibitors reduced mortality, cardiovascular events and hospitalization for heart failure. However, those trials were not specialized design to investigate the effect of sodium-glucose cotransporter 2 inhibitors in patients with heart failure, in particular with heart failure with preserved ejection fraction. Purpose The aim of this study was to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) in type 2 diabetes patients with heart failure with preserved ejection fraction. Methods This study was a prospective, multicenter, open-label, randomized-controlled trial, comparing luseogliflozin 2.5 mg once daily or voglibose 0.2 mg three times daily in patients with type 2 diabetes suffering from heart failure with preserved ejection fraction (left ventricular ejection fraction >45% and BNP ≥35 pg/ml2) in a 1:1 randomization fashion. Randomization was undertaken using a computer-generated random sequence web response system. The primary outcome was the difference from baseline in BNP after 12 weeks of treatment between two drugs. The key secondary outcomes were the change from baseline in left ventricular ejection fraction and E/e' in echocardiographic parameters, body weight, glycohemoglobin level after 12 weeks of treatment. The safety outcomes included the incidence of major adverse cardiovascular events, hypoglycemic adverse events, and urinary tract infection. Results Between December 2015 and September 2018, 173 patients from 16 hospitals and clinics have been included in this study. Of those, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in the BNP concentration after 12 weeks from baseline between the two groups; the ratio of the average values at week 12 to the baseline value was 0.91 in the luseoglifllzin group as compared with 0.98 in the voglibose group (percent change, −9.0% vs. −1.9%, ratio of change with luseogliflozin vs. voglibose, 0.93; 95% confidence interval, 0.78 to 1.10; p=0.26). The key secondary outcomes including left ventricular ejection fraction, E/e', body weight, glycohemoglobin level and the safety outcomes did not differ significantly between the two groups. Conclusions In type 2 diabetes patients with heart failure with preserved ejection fraction, the administration of luseogliflozin did not lead to a significant reduction in the BNP concentration than that of voglibose. Left ventricular ejection fraction, E/e', body weight and glycohemoglobin level after 12 weeks of treatment, comparing with at baseline did not differ significantly between the two groups. (UMIN Clinical Trial Registry number, UMINehz748.005618395) Acknowledgement/Funding Novartis

P1642High-sensitivity cardiac troponin I and NT-proBNP and their relationship to heart failure in the European BiomarCaRE population

Abstract Aims Heart failure (HF) is an increasingly important contributor to the overall burden of cardiovascular disease in the population. We aimed to determine the distribution of the cardiac biomarkers high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations across the European population to characterize the association with incident HF. Methods and results Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 48,455 individuals from four prospective population-based cohort studies (DanMONICA, FINRISK, Moli-Sani, Northern Sweden MONICA study) across Europe with a maximum follow-up of 27 years. The median age of the participants was 50.7 years (25th percentile: 40.0 years, 75th percentile: 61.7 years) and 49.1% (25,146) were men. Considered endpoints were incident HF and all-cause mortality. The median follow-up time for occurrence of HF was 6.61 (6.55; 6.66) years. We found that cardiovascular risk factors (CVRFs), especially diabetes with HR of 2.11 (95% CI 1.8, 2.5) and smoking status with HR of 1.79 (95% CI 1.59, 2.1) (Figure 1) were associated with incident HF. Furthermore, beyond the CVRFs, elevated hs-cTnI and NT-proBNP concentrations contributed to risk of HF in the general population with HR of 1.49 (95% CI 1.21, 1.9) and HR of 2.37 (95% CI 1.97, 3.0) respectively. As a cut-off value to select individuals, who would benefit most from preventive strategies, a hs-cTnI concentration of 2.8 ng/L was calculated using the optimal cut-off methodology by Contal and O'Quigley in CSDA 1999. Hazard ratio for incident HF Conclusion In our large population-based cohort, hs-cTnI and NT-proBNP were independently associated with incident HF. Use of biomarkers for HF screening thus may help to select those individuals in the general population who would benefit most from preventive strategies. Based on the cut-off value future studies are needed to evaluate therapeutic options.

BNP as a marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.

Anthracycline chemotherapy serves an important role in treating patients with breast cancer but is associated with cardiotoxicity. Although brain natriuretic peptide (BNP) is not the ideal marker for detecting the presence of diseases of the heart, several studies have demonstrated the predictive utility of BNP in the diagnosis of anthracycline-induced cardiotoxicity (AIC). The aim of the present study was to evaluate the role of BNP as a marker for the early prediction of AIC in patients with breast cancer. In the present study, a total of 149 patients with breast cancer who received anthracycline therapy were evaluated. The levels of BNP and echocardiography were detected during the anthracycline-based chemotherapy and patients were followed up after chemotherapy to determine the cardiotoxicity-free survival times. In the patients who received chemotherapy, an increase in the levels of BNP was observed. The concentration of BNP was significantly higher in the cardiotoxicity group during anthracycline chemotherapy (P=0.022) compared with the non-cardiotoxicity group and it was an independent predictor of cardiotoxicity (P=0.028). The optimal diagnostic threshold of BNP after the last anthracycline chemotherapy treatment was 107.9 pg/ml, the diagnostic sensitivity was 0.538, the specificity was 0.794, the Youden index was 0.332, the positive predictive value was 0.583 and the negative predictive value was 0.762. Based on the BNP threshold, a log-rank test was performed and it was determined that the cardiotoxicity-free survival rate of the group with higher levels of BNP was always lower compared with the group with lower levels of BNP. BNP elevation was associated with cardiotoxicity during the anthracycline chemotherapy. Detecting BNP after the final treatment of anthracycline chemotherapy may contribute to the early detection of cardiotoxicity.

Brain natriuretic peptide in the diagnosis of structural and functional changes of the myocardium in men with uncomplicated and asymptomatic hypertension with polymorphic variants of aldosteronesynthase gene

According to previous studies, aldosterone is responsible for myocardial remodeling and, ultimately, myocardial dysfunction. Aldosterone synthase gene (CYP11B2) as the main controller of aldosterone may be involved in the variability of renin-angiotensin-aldosterone system (RAAS) activity. Brain natriuretic peptide (BNP) is a marker for the diagnosis of chronic heart failure and it’s a contraregulatory peptide of RAAS. The aim of our study was to investigate the levels of BNP plasma concentrations in men with uncomplicated hypertension, carriers of polymorphic variants of the CYP11B2 gene. The study involved 150 men: 50 men of control group and 100 men of main group patients with hypertension of I-II stages. Each participant underwent office blood pressure measurement, echocardiography, determination of plasma levels of BNP in serum by immunoassay (ELISA) and determination of C-344T polymorphism of CYP11B2 gene in venous blood samples by PCR. Mathematical processing of obtained data was performed using standard statistical package STATISTICA 10.0. In accordance with the normal distribution, obtained results were presented as mean and standard deviation. In case of discrepancy of normal distribution a median of 25-75% of quartiles, including half of all parameter values, was given. For comparing groups by investigated parameters, the Student's t test was used for normal distribution, and in the absence of normal distribution, its non-parametric analogs were used: the Mann-Whitney or ANOVA test. It was found that male carriers of CC polymorphism of CYP11B2 gene had higher plasma concentrations of BNP and in the group of patients with essential hypertension and left ventricle hypertrophy (LVH) the representatives of this polymorphic variant of CYP11B2 gene had more severe diastolic disorders and signs of myocardial remodeling. The TT carrier of the CYP11B2 gene polymorphism was associated with excess body mass and lower BNP levels.

Cardiomegaly of the larger twin in monochorionic twin pregnancies warrants neonatal intensive care even without twin-to-twin transfusion syndrome

ObjectivesSome monochorionic twin pregnancies need intensive cardiac management even in the absence of twin-to-twin transfusion syndrome after birth. The purpose of this study was to investigate risk factors related to persistent hypotension requiring cardiotonic agent use among monochorionic twin pregnancies without twin-to-twin transfusion syndrome. Study designThis was a retrospective study of 316 monochorionic twin pregnancies without twin-to-twin transfusion syndrome (632 babies). All cases were treated in the neonatal intensive care unit. Hypotension was defined as mean arterial blood pressure below the norm for gestational age. Decreased left ventricular ejection fraction was defined as a value <60%. Dopamine, dobutamine and phosphodiesterase III inhibitor were used as cardiotonic agents for hypotension persisting even after adequate infusion. ResultsAmong the 632 cases, 33 (5.2%) needed cardiotonic agents for persistent hypotension. The frequency of persistent hypotension with decreased left ventricular ejection fraction was significantly higher among larger twins (4.4%) than among smaller twins (0.6%, p = 0.0038). In larger twins, multivariate analysis showed that Z-score for cardiothoracic area ratio (odds ratio, 2.31; p < 0.001), tricuspid regurgitation (odds ratio, 6.34; p = 0.015) and gestational age at delivery (odds ratio, 0.66; p < 0.001) correlated with persistent hypotension. In smaller twins, univariate analysis showed gestational age at delivery, birth weight, Z-score for birth weight and Z-score for cardiothoracic area ratio of the larger twin were related to persistent hypotension. Concentration of brain natriuretic peptide in the umbilical vein in larger and smaller twins were significantly correlated (coefficient of correlation = 0.792, p < 0.001). ConclusionsIn monochorionic twin pregnancies, attention needs to be given to cardiac size along with amniotic fluid and fetal growth. Both larger and smaller twins carry risks of persistent hypotension after birth. Close observation is needed, especially in cases where the larger twin displays cardiomegaly despite absence of twin-to-twin transfusion syndrome.

Prognostic significance of serum cholinesterase in patients with acute decompensated heart failure: a prospective comparative study with other nutritional indices

Nutritional status is associated with poor outcomes in patients with heart failure. Serum cholinesterase (CHE) concentration, a marker of malnutrition, was reported to be a prognostic factor in patients with chronic heart failure. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are established objective nutritional indices. The aim of this study was to clarify the prognostic significance of CHE concentration and to compare it with other well-established objective nutritional indices in patients with acute decompensated heart failure (ADHF). We prospectively enrolled 371 consecutive patients admitted for ADHF with survival discharge. Laboratory data including CHE and the objective nutritional indices were obtained at discharge. The primary endpoint of this study was all-cause mortality. During a mean ± SD follow-up period of 2.5±1.4 y, 112 patients died. CHE concentration was significantly associated with all-cause mortality independently of GNRI, CONUT score, or PNI, after adjustment for major confounders including other nutritional indices, such as age, sex, systolic blood pressure, BMI, left ventricular ejection fraction, history of hypertension, diabetes mellitus, dyslipidemia, prior heart failure hospitalization, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, β-blocker use, statin use, hemoglobin, sodium, blood urea nitrogen, albumin, C-reactive protein, and brain natriuretic peptide concentrations via multivariable Cox analysis. Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with CHE stratum [lowest tertile: 53%, adjusted HR: 6.92; 95% CI: 3.87, 12.36, compared with middle tertile: 28%, adjusted HR: 2.72; 95% CI: 1.45, 5.11, compared with highest tertile: 11%, adjusted HR: 1.0 (reference), P<0.0001]. CHE showed the best area under the curve value (0.745) for the prediction of all-cause mortality compared with the other objective nutritional indices. Net reclassification improvement afforded by adding CHE to the fully adjusted multivariable model was statistically significant for all-cause mortality (0.330; 95% CI: 0.112, 0.549, P=0.0030). CHE is a simple, strong prognostic marker for the prediction of all-cause mortality in patients with ADHF.

The acute effects of anaerobic exercise in the morning and evening on brain natriuretic peptide (BNP) in women with the Metabolic Syndrome

Background: Brain natriuretic peptide (BNP) in terms of pathological is an important indicator for evaluation and detection left ventricular systolic dysfunction. It seems that physical activity and circadian rhythms are effective on BNP concentration. The aim of this study was to investigate the acute effects of anaerobic exercise in the morning and evening on brain natriuretic peptide in women with Syndrome Metabolic. Methods: 17 women 30-40 years of age with Metabolic Syndrome were selected voluntarily and purposefully participated in the study. Then in two separate sessions (within 6 days) anaerobic exercise perfoemed in the morning and evening. Blood samples were collected before and immediately after exercise in the morning and evening. Results: The BNP concentrations significantly increased after exercise in the morning and evening (P˂0.000). There was significant difference between morning and evening in BNP concentration after exercise (P˂0.002). Conclusion: Considering the significant difference in the mean BNP concentration in the morning and evening, due to the lower average of BNP concentration in the evening it seems activity in the evening have less stress on the myocardial wall.

N-terminal pro brain natriuretic peptide eliminates the prognostic effect of atrial fibrillation in patients with chronic heart failure.

AimsCo‐morbid atrial fibrillation (AF) increases both mortality and N‐terminal pro brain natriuretic peptide (NT‐proBNP) concentrations in patients with chronic heart failure (CHF). It is unclear whether AF worsens prognosis independently from NT‐proBNP concentrations. If AF was an independent risk factor, NT‐proBNP levels for outcome prediction would need to be adjusted in patients with AF. We aimed to analyse the influence of AF on the prognostic value of NT‐proBNP in patients with CHF.Methods and resultsA total of 2541 consecutive CHF patients with sinus rhythm (SR) or AF were identified in the outpatients' CHF registry of the University of Heidelberg, Germany. Of these, 250 patients with SR were individually matched to 250 patients with AF with respect to NT‐proBNP, New York Heart Association functional class, sex, age, and aetiology of CHF. In the general sample, both AF and NT‐proBNP were associated with all‐cause mortality [hazard ratio (HR) = 1.96, 95% confidence interval (CI) 1.61–2.39, P < 0.001; and HR = 1.03 per 1000 ng/L increase, 95% CI 1.02 to 1.04, P < 0.001, respectively]. After matching, NT‐proBNP retained its prognostic power (HR = 1.13 per 1000 ng/L increase, 95% CI 1.10 to 1.16, P < 0.001), but AF did not (HR = 0.91, 95% CI 0.66 to 1.25, P = 0.56). Despite similar prognosis, matched patients with SR were in more advanced CHF than were AF patients as indicated by a lower left ventricular ejection fraction (30 ± 13% vs. 34 ± 14%, P < 0.001).ConclusionsThe prognostic value of NT‐proBNP in CHF is not influenced by concomitant AF. AF, in return, might be a surrogate of a worse cardiac condition rather than an independent risk factor.

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).

AIN-93 Diet as an Alternative Model to Lieber-DeCarli Diet for Alcoholic Cardiomyopathy.

The Lieber-DeCarli alcoholic liquid diet is a classical method for establishing animal models of alcoholic cardiomyopathy (ACM). No study has reported whether the AIN-93 diet, which is widely used as a standard diet for both long-term and short-term studies with laboratory animals, could be used to construct the ACM animal model. The present study intended to investigate whether the AIN-93 diet could be used to establish a mouse ACM model. Twenty-four C57BL/6 male mice were randomly divided into 4 equally sized groups. In ethanol (EtOH)-fed groups, mice were fed a 4%-EtOH (w/v, 28% of total calories) alcoholic liquid diet of Lieber-DeCarli or the AIN-93 diet for chronic alcohol exposure for 180days. In control-fed groups, mice were fed with non-EtOH liquid diets with the same calories as EtOH-fed groups. Morphological observations of the hearts and molecular investigation of the brain natriuretic peptide (BNP) were carried out by echocardiography, hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay. Echocardiography showed that mice fed with either the 4%-EtOH Lieber-DeCarli diet or the 4%-EtOH AIN-93 diet had dilated ventricles and poor cardiac function. IHC staining of BNP, qPCR of BNP mRNA, and plasma concentration of BNP showed an up-regulated expression in mice fed with both the 4%-EtOH Lieber-DeCarli and 4%-EtOH AIN-93 diets. Less fatty liver was also observed in mice fed the AIN-93 alcoholic diet than those fed the Lieber-DeCarli alcoholic diet. The AIN-93 alcoholic liquid diet can be used to establish ACM animal models, as with the conventional Lieber-DeCarli alcoholic liquid diet.

Markers of maternal cardiac dysfunction in pre-eclampsia and superimposed pre-eclampsia

AuthorsFrances Conti-Ramsden MBBS Academic Clinical Fellow1, Carolyn Gill PhD BRC Research Assistant1, Paul T Seed MSc CStat Senior Lecturer in Medical Statistics1, Kate Bramham PhD Clinical Senior Lecturer in Nephrology2, Lucy C Chappell PhD NIHR Research Professor in Obstetrics1, Fergus P McCarthy PhD Clinical Senior Lecturer in Obstetrics and Gynaecology1,3. ObjectivesTo determine whether glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations are elevated in pre-eclampsia and superimposed pre-eclampsia (SPE), demonstrating cardiac ischaemia and strain. Study designA nested case-control study was performed using samples and clinical data available from a prospective pregnancy cohort. Four groups were selected: healthy pregnant controls (n = 21), pre-eclampsia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20) or with superimposed pre-eclampsia (SPE) (n = 19). Plasma samples were taken at time of disease or the third trimester in controls. Main outcome measuresPlasma concentrations of GPBB and BNP. ResultsThere was no significant difference in GPBB plasma concentrations between controls and pre-eclampsia (geometric mean (GM) [95% CI]: 4.74 [2.54–8.84]ng/mL vs 5.01 [2.58–9.74]ng/mL, p = 0.90)), or between CHT and/or CKD and SPE (GM [95% CI]: 9.49 [4.93–18.25]ng/mL vs 10.24 [5.27–19.92]ng/mL, p = 0.87). BNP plasma concentrations were significantly raised in women with pre-eclampsia compared to controls (GM [95% CI]: 31.83 [20.18–50.22]pg/mL vs 11.33 [7.34–17.51]pg/mL, p = 0.001). Women with CKD, but not CHT, who developed SPE had elevated BNP concentrations. There were no significant differences in BNP concentration between women with comorbidity (CHT and/or CKD) and controls. ConclusionsGPBB has a limited role as a biomarker in hypertensive disorders of pregnancy. BNP concentrations were elevated in pre-eclampsia compared to controls. This suggests cardiac strain at the time of pre-eclampsia. Further studies are needed to examine whether BNP can identify women at increased risk of cardiovascular disease.

Myocardial Contractile Function in Patients with Liver Cirrhosis and Syndrome of Bacterial Overgrowth Syndrome

to study myocardial contractile function in patients with liver cirrhosis and ascites in the presence of bacterial overgrowthsyndrome (BOS) and pathological bacterial translocation. We included in this study 59 patientswith Child-Pugh class B and C liver cirrhosis (LC) of various etiology and ascites. Control group comprised 12 patients withischemic heart disease complicated by chronic heart failure (CHF). Examination included history taking and laboratory andinstrumental investigation. LC was diagnosed basing on clinical symptoms and instrumental studies. Child-Pugh and MELDscores were used for assessment of LC severity and prognosis. International ascites club grading system was used for evaluationof severity of ascites. Hydrogen breath test was applied for diagnosing BOS. Syndrome of pathological bacterial translocationwas established based on blood levels of lipopolysaccharide-binding protein and detection of bacterial DNA in ascitic fluid.Structural-functional parameters of the myocardium and hemodynamics were assessed by echocardiography. Brain natriureticpeptide (BNP) concentration was measured in blood serum and ascitic fluid. In 13 of 59 patients with LC the hydrogenbreath test was negative, in 33 positive and in 13 patients the positive hydrogen test was combined with the presence of BOSand pathological bacterial translocation. Blood serum and ascitic fluid BNP concentrations in LC patients were low and withinnormal limits (62.5±4.1 and 53.3±4.9 rg / ml, respectively), what contrasted with high BNP concentrations in patients withCHF (1820±95.5 and 497.1±39.6 rg / ml, respectively). Total protein level in ascitic fluid also was significantly lower in patientswith LC than in patients with CHF (1.77±0.1 and 4.43±0.35 mg / dL, respectively). The serum-ascitic albumin gradient(SAAG) in both groups of patients exceeded 1.1 (1.58±0.13 in patients with CHF and 1.88±0.19 in patients with LC).Conclusions. In patients with liver cirrhosis the presence of BOS and bacterial translocation did not produce a distinct negativeimpact on contractile function.

MON-619 The Direct Stimulatory Effect of Thyroid Hormone Against Plasma Brain Natriuretic Peptide in Health Check-Up Participants: Cross-Sectional and Longitudinal Studies

Background: Circulating levels of thyroid hormone (TH) and TSH may not always reflect TH activity in specific peripheral tissues. Although the heart is one of the major target organs for TH, the tissue-specific circulating markers of TH activity have not been characterized. Therefore, we investigated the independent effects of TH status on plasma brain natriuretic peptide (BNP) concentrations in a large number of health check-up participants. Methods: We retrospectively analyzed data from participants who visited our hospital for health check-ups between July 2008 and March 2017. Among 20,403 participants, 12,409 revisited periodically. Participants were included in the cross-sectional study population if measurements of their concurrent TSH, free T4, body mass index, systolic blood pressure, hemoglobin, and estimated glomerular filtration rate were available at the initial visit. Longitudinal analysis was performed if the concurrent results for the participants were consecutively available. Exclusion criteria were abnormal electrocardiogram and/or a history of cardiac disease. Results: In the cross-sectional study (n = 2,807), multivariate analyses demonstrated a significant elevation in BNP (logarithmically converted) in overt thyrotoxicosis (OT; n = 21) compared with euthyroidism (n = 2,629), but not in subclinical thyrotoxicosis (SCT; n = 53), subclinical hypothyroidism (SCH; n = 97), or overt hypothyroidism (OH; n = 7). However, the standardized partial regression coefficient for thyroid function category against BNP was the lowest (β = 0.048, p = 0.006) among several other independent variables. After participants with OT or OH were excluded because of the small group size, the longitudinal study (n = 990) demonstrated no significant differences in the annualized rate of change in BNP among SCT (n = 4), SCH (n = 963), and euthyroidism (n = 23). Conclusions: The direct stimulatory effects of TH on BNP were only confirmed for OT. Our study suggests that plasma BNP concentrations are not sufficiently sensitive to evaluate TH activity in the heart. Physicians should consider multiple independent contributing factors other than thyroid dysfunction when interpreting BNP data in patients with thyroid disorders.

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 reflects individual variation in hydration status in hemodialysis patients.

Introduction: Fluid management in hemodialysis patients is a controversial topic. Brain natriuretic peptide (BNP) is secreted from the heart in response to volume overload, and may be a marker of overhydration in hemodialysis patients. Our aim was to investigate the correlation between BNP and overhydration in a cohort of hemodialysis patients, and to find out whether BNP and overhydration correlate in repeated measurements within individuals with elevated BNP. Methods: The study was prospective, observational, and had a cross‐sectional part and a longitudinal follow‐up. The distribution of BNP was investigated in a cohort of 64 hemodialysis patients. Blood samples and bioimpedance spectroscopy measurements were performed before midweek dialysis. Subsequently, 11 study participants with elevated BNP concentrations (>500 pg/mL) were assessed in another nine dialysis sessions each. These individuals also had their cardiac function and heart rate variability (HRV) examined. Findings: BNP was above 500 pg/mL in 38% of the participants, and correlated positively with overhydration (rs = 0.381), inflammation and malnutrition, but not with systolic blood pressure. In comparison to participants with BNP below 500 pg/mL, participants with elevated BNP were older, had lower muscle strength, lower bodyweight and lower levels of hemoglobin and albumin. Echocardiography revealed cardiac anomalies in all 11 participants in the longitudinal follow‐up, and HRV, as measured by SDNN, was pathologically low. In repeated measurements, the between‐individuals variation of BNP in relation to overhydration was greater (SD = 0.581) than the within‐person variation (SD = 0.285). Discussion: BNP correlates positively to overhydration, malnutrition, and inflammation. In a subgroup of patients with elevated BNP, who are mainly elderly and frail, BNP reflects individual variation in hydration status, and hence seems to be a modifiable marker of overhydration. These data suggest that BNP is best applied for measuring changes in hydration status within an individual over time.

The Relationship of Appetite-Regulating Hormones in the Development of Cardiac Cachexia.

The physiological control of appetite regulation involves circulating hormones with orexigenic (ghrelin) and anorexigenic (cholecystokinin) properties that induce alterations in energy intake via perceptions of hunger and satiety. We sought to investigate the relationship between appetite-regulating hormones and the cachexia associated with chronic heart failure.We randomized male Sprague-Dawley rats into myocardial infarction (MI) or sham operation (SO) groups. The levels of brain natriuretic peptide (BNP), cholecystokinin (CCK) and ghrelin in the plasma of all rats were detected by enzyme-linked immunosorbent assay (ELISA); the expression of BNP, CCK, and ghrelin in the myocardial tissue of all rats were detected by western blotting, immunohistochemistry, real-time polymerase chain reaction (PCR); myocardial morphology was assessed by microscopy.Plasma BNP and CCK levels in the cardiac cachexia (CC) groups and the heart failure non-cachexia (HF-nc) groups were significantly higher than those in the control groups (P < 0.01), and the expression of BNP and CCK in the myocardial tissue of rats: in CC groups and HF-nc groups were increased compared with the corresponding control groups (P < 0.01). In contrast, Plasma and cardiac expression of ghrelin decreased compared with the sham group (P < 0.01). Furthermore, plasma CCK levels were positively correlated with BNP concentrations (P < 0.001) and significantly negatively correlated with the ejection fraction (P < 0.001) in model animals; plasma ghrelin levels were negatively associated with BNP levels (P = 0.0023) and positively associated with ejection fraction (P = 0.0042).The appetite-regulating hormones (ghrelin and CCK) may present as a potential significant biomarker for cachexia associated with chronic heart failure.

Association between left ventricular ejection fraction and Kawasaki disease shock syndrome.

This study was performed to explore the clinical features of Kawasaki disease shock syndrome and analyse the association between the left ventricular ejection fraction and Kawasaki disease shock syndrome. We retrospectively reviewed the medical records of all consecutive inpatients with Kawasaki disease at Wenzhou Medical University Second Affiliated Hospital and Yuying Children's Hospital in Wenzhou, China from January 2009 to December 2016. We compared the clinical characteristics, laboratory data, and left ventricular ejection fraction between patients with and without Kawasaki disease shock syndrome and analysed the effect of the left ventricular ejection fraction on Kawasaki disease shock syndrome under different clinical conditions of Kawasaki disease. In total, 1147 patients were diagnosed with Kawasaki disease. Of these 1147 patients, 17 were diagnosed with Kawasaki disease shock syndrome; 68 patients admitted to the hospital at the same time, ±2 weeks, with Kawasaki disease but without Kawasaki disease shock syndrome served as the control group. Compared with the control group, the Kawasaki disease shock syndrome group had a significantly higher incidence of coronary artery lesions, cardiac troponin I concentration, N-terminal prohormone of brain natriuretic peptide concentration, neutrophil count and ratio, alanine aminotransferase concentration, aspartate aminotransferase concentration, and C-reactive protein concentration and a significantly lower platelet count, serum albumin concentration, and left ventricular ejection fraction. A low left ventricular ejection fraction was associated with Kawasaki disease shock syndrome under different conditions of Kawasaki disease. Among patients with Kawasaki disease, cardiac injury is more likely in those with Kawasaki disease shock syndrome than without, and a low left ventricular ejection fraction may be associated with the development of Kawasaki disease shock syndrome.

Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial

ObjectiveTo test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. MethodsThis was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90 pg/mL and a Borg dyspnea score ≤ 2. The sample size of N = 76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha = 5%. ResultsWe randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P = 0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P = 0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 h (P = 0.010, Cochrane's Q test). ConclusionsIn patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography. Clinical trial registrationNCT01939301.

Renal denervation in patients with symptomatic chronic heart failure despite resynchronization therapy - a pilot study.

IntroductionRenal denervation (RD) has been shown to decrease sympathetic function in patients with hypertension. Its efficacy in symptomatic chronic heart failure (CHF) patients not responding to cardiac resynchronization therapy (CRT) has not been evaluated.AimTo assess whether a less invasive treatment method – renal denervation – is safe in symptomatic heart failure patients despite optimal medical treatment and resynchronization therapy and whether it is associated with an improvement in clinical status, exercise capacity and hemodynamic parameters.Material and methodsThe study was an open-label, randomized, controlled clinical trial. Patients were divided into an intervention (RD) and a control group. Clinical data collection, blood pressure (BP) measurements, echocardiography, 6-minute walk test (6MWT) and laboratory tests were performed before, 6 and 12 months after RD. The patients were followed-up to 24 months.ResultsWe included 20 patients aged 52.0 to 86.0 years (median age: 71.5 years), 15 males and 5 females with median left ventricular ejection fraction (LVEF) of 32.5%, body mass index 31.3 kg/m2. Renal denervation was safe, no significant adverse effects were registered. There were no significant differences in LVEF, BP, 6MWT and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration 6 and 12 months after RD or control.ConclusionsOur results indicate that RD in CHF patients not responding to CRT is safe and does not worsen exercise capacity and hemodynamic parameters.

Possible involvement of thiamine insufficiency in heart failure in the institutionalized elderly.

Heart failure is a major manifestation of thiamine deficiency; beriberi. Even thiamine insufficiency, milder than deficiency, may be associated with increased heart failure risk. In this cross-sectional study, the relationship between thiamine insufficiency and heart failure was investigated in the Japanese institutionalized elderly from April to November 2017. Fifty-five subjects in four care facilities were evaluated for their whole blood thiamine and plasma brain natriuretic peptide concentrations. Mean whole blood thiamine concentration was 88.7 ± 22.3 nmol/L in men and 92.0 ± 16.5 nmol/L in women, and significantly and negatively correlated with plasma brain natriuretic peptide concentrations (r = −0.378, p = 0.007). In the multiple regression analysis adjusted by age, sex, body mass index, and eGFR, whole blood thiamine concentration was a significant negative contributor (standardized coefficient β = −0.488, p = 0.001) to plasma brain natriuretic peptide. In the logistic regression analysis adjusted by the same variables, whole blood thiamine concentration significantly contributed to plasma brain natriuretic peptide concentration higher than over 40 pg/ml (OR: 0.898, 95%CI: 0.838–0.962). Whole blood thiamine concentration in subjects with diuretics was significantly lower than those without it (p = 0.023). Thiamine insufficiency was related to increased plasma brain natriuretic peptide concentration and may increase the risk of heart failure.