Plasma Brain Natriuretic Peptide Concentration Research Articles

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85

ObjectiveTo investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85.MethodsOne hundred patients (four cases excluded) aged 70–85 years, with body mass index 18–24 kg·m−2 and American Society of Anesthesiologists physical status II–III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg−1·h−1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid–binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted.ResultsCompared with group C, MAP was significantly higher at T1–T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia.ConclusionsLow-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury.Trial registrationThis study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

Dapagliflozin treatment and cardiovascular outcome in RBP4/TTRVal30Met (transthyretin cardiac amyloidosis) mice.

Whether sodium-glucose co-transporter 2 inhibitors are effective for heart failure caused by ATTR-CA (transthyretin cardiac amyloidosis) remains uncertain. The aim of this study is to investigate the cardiovascular prognosis in ATTR-CA mice model with dapagliflozin treatment. Humanized RBP4/TTRVal50Met and RBP4/TTR mice models were constructed with clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) techniques and multiple generations breeding. A total of 6 RBP4/TTR mice received placebo treatment, when 12 RBP4/TTRVal50Met received dapagliflozin (1mg/kg/day, 6 mice) and placebo (6 mice) treatment. Fasting glucose, intraperitoneal glucose tolerance test, and plasma brain natriuretic peptide (BNP) concentration were measured at Day 0, Week 2, and Week 4. BNP, transforming growth factor-beta (TGF-β), collagen type I alpha 1 (COL1A1) protein levels, and Cola1, TGFβ1, TNFα, IL-1β, BNP relative quantities in cardiac, along with cardiac pathology examination including right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter were measured at Week 4 after treatment procedure. All 18 mice completed the experiment. The baseline characteristics were balanced among three treatment groups. In placebo-treated mice, the cardiac BNP relative quantity was significantly higher in RBP4/TTRVal50Met mice than RBP4/TTR mice (RBP4[KI/KI], TTR [KI/KI]: 0.72±0.46, RBP4[KI/KI], TTRVal50Met [KI/KI]: 1.44±0.60, P=0.043), indicating more significant heart failure progression in ATTR-CA mice than normal mice. In ATTR-CA mice, the cardiovascular prognosis measurements including heart failure (plasma BNP concentration and relative quantities of BNP), cardiac inflammation (relative quantities of Cola1, TGFβ1, TNFα, and IL-1β), and pathological changes (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were statistically comparable between those under dapagliflozin and placebo treatment. Dapagliflozin did not improve cardiovascular prognosis including the progression of heart failure, cardiac inflammation, and pathological changes in ATTR-CA mice compared with placebo. The results of this study were not in support of dapagliflozin's therapeutic effects for ATTR-CA. More pre-clinical and clinical researches to validate these findings and demonstrate the underlying mechanisms are still required.

The impact of COVID-19 on BNP, NT-proBNP and ANP in heart failure.

Extensive research has been conducted on biomarkers associated with coronavirus disease 2019 (COVID-19) in both healthy individuals and those with various conditions, particularly heart diseases. However, there is a limited investigation into the relationship between widely used cardiac biomarkers known as natriuretic peptides, including Brain natriuretic peptide (BNP), N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and Atrial natriuretic peptide (ANP), and COVID-19 infection specifically in patients with heart failure. These natriuretic peptides assess the hemodynamic stress on the heart wall and have the potential to serve as biomarkers for evaluating the severity of COVID-19 infection in heart failure patients. Therefore, this study aimed to assess the plasma concentration of BNP, NT-proBNP, and ANP in a medium-sized cross-sectional case-control study involving 360 heart failure patients, both infected and uninfected with COVID-19. The heart failure patients were categorized into subgroups based on their Ejection Fraction (EF) percentage, namely heart failure with reduced EF (HFrEF), heart failure with mid-range EF (HFmrEF), and heart failure with preserved EF (HFpEF). Our findings demonstrate a significant increase in plasma levels of BNP and NT-proBNP in all heart failure patients, as well as in each subgroup (HFrEF, HFmrEF, and HFpEF) when infected with COVID-19, compared to uninfected heart failure patients. These established cardiac biomarkers have the potential to be utilized as future indicators for assessing the severity of COVID-19 infection in heart failure patients, thereby enhancing heart failure management and reducing irreversible cardiac damage.

PO-638-04 LOW ATRIAL NATRIURETIC PEPTIDE TO BRAIN NATRIURETIC PEPTIDE RATIO WAS ASSOCIATED WITH LEFT ATRIAL REMODELING AND HOSPITALIZATION DUE TO HEART FAILURE IN PATIENTS WITH ATRIAL FIBRILLATION ABLATION

Deficiency of atrial natriuretic peptide (ANP) is thought to contribute to hemodynamic deterioration in case with advanced atrial remodeling due to atrial fibrillation (AF). However, little is known about the association between plasma ANP level and severity of left atrial remodeling or prognosis of heart failure in patients with AF. The purpose of this study was to investigate the association between ANP and left atrial remodeling or prognosis of heart failure in patients with AF ablation. Three hundred and seventy-three consecutive patients who underwent initial ablation for persistent AF (age, 67 ± 10 years; and females, 97 [26%]) were retrospectively enrolled. Plasma ANP and brain natriuretic peptide (BNP) concentration were measured before the procedure and ANP/BNP ratio was calculated. Left atrial appendage emptying velocity (LAAEV), left atrial low voltage areas (LVAs), and left atrial volume index (LAVI) were used as clinical factors of left atrial remodeling. Median plasma ANP level was 116 (71-178) pg/ml, and median ANP/BNP ratio was 0.65 (0.46-1.00). Plasma ANP levels did not correlated with LAAEV or LVAs. There was significant correlations between ANP/BNP ratio and LAAEV, LVAs, or LAVI. During the 24 months follow-up, freedom from hospitalization due to heart failure was significantly lower in patients with a ANP/BNP ratio ≤ 0.65 than in those with a ANP/BNP ratio > 0.65 (94.3% versus 99.5%, P<0.01). The secretion of ANP relative to BNP decrease along with progression of left atrial remodeling in patients with AF ablation. Additionally, hospitalization due to heart failure frequently occurred in patients with low secretion of ANP relative to BNP.

ASA Status, NPPA/NPPB Haplotype and Coronary Artery Disease Have an Impact on BNP/NT-proBNP Plasma Levels.

Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels.

Association between elevated brain natriuretic peptide levels and weaning failure: A systematic review and meta-analysis.

Cardiovascular dysfunction has been reported as an important mechanism of weaning failure, and recent data suggest that elevated brain natriuretic peptide (BNP) levels is associated with an increased risk of weaning failure. Therefore, we performed this meta-analysis to evaluate the correlation between elevated BNP levels and weaning failure in critically ill patients subject to mechanical ventilation. A systematic search in Cochrane Library, Embase, PubMed and Web of Science was performed up to September 25, 2019. Standard mean differences (SMD) and corresponding 95% confidence intervals (CIs) of the BNP levels were calculated for each study. Nine studies with a total number of 589 were included in the final meta-analysis. The results showed that elevated BNP levels were significantly associated with the risk of weaning failure (SMD: 0.76, 95% CI: 0.47 to 1.05, P<.00001). The finding was consistent with the BNP measured before (SMD: 0.68, 95% CI: 0.26 to 1.11, P=.002) or at the end of spontaneous breathing trial (SBT) (SMD: 0.85, 95% CI: 0.52 to 1.18, P<.00001). This meta-analysis showed that increased plasma BNP concentration was associated with weaning failure in ICU patients.

Effect of Acupoint Meridian Therapeutic Exercise on Cardiac Function in Patients with Chronic Heart Failure

Objective: To investigate the effect of acupoint meridian therapeutic exercise on cardiopulmonary function in patients with chronic heart failure (CHF).&lt;br/&gt; Methods: One hundred patients diagnosed with CHF at the Department of Cardiology from June 2019 to October 2019 were enrolled. One hundred patients were randomly divided into an experimental group (n = 50) and a control group (n = 50) according to the treatment they received. The experimental group received conventional treatment combined with acupoint meridian therapeutic exercise for three months. The patients in the two groups were compared in terms of their results on the six-minute walk test and their cardiac function grade, plasma brain natriuretic peptide (BNP) concentration, left ventricular ejection fraction (LVEF), and quality of life.&lt;br/&gt; Results: A statistically significant increase in six-minute walking distance was observed in the experimental group compared with the control group. Cardiac function and plasma BNP concentration decreased and LVEF and quality of life increased.&lt;br/&gt; Conclusion: Acupoint meridian therapeutic exercise improves exercise tolerance, cardiopulmonary function, and quality of life in patients with CHF.

BNP and NT-proBNP Concentrations in Paired cerebrospinal Fluid and Plasma Samples of Patients with Traumatic Brain Injury

The aim of this study was to investigate the secretion patterns of brain natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) after traumatic brain injury (TBI) and to analyze the source of them in cerebrospinal fluid (CSF). We synchronously measured BNP and NT-proBNP concentrations in paired CSF and plasma samples from 22 moderate to severe TBI patients and 40 healthy control patients. The CSF and/or plasma ratio of albumin (QAlbumin) was calculated daily. The BNP and NT-proBNP levels of CSF and plasma were compared between TBI patients and control patients. CSF BNP and NT-proBNP levels peaked on day 3 after injury, as did the plasma BNP and NT-proBNP levels. The CSF BNP and NT-proBNP levels in TBI patients were elevated from day 1, which was significantly higher than control group (P < 0.05 and P < 0.01, respectively). However, in plasma, only NT-proBNP levels were significantly higher than in the control group from day 2 (P < 0.05). In addition, QBNP, defined as CSF BNP concentration and/or plasma BNP concentration, was significantly higher in TBI patients than in the control group (P < 0.01). However, QAlbumin remained within ranges of a mild to moderate dysfunction of blood-brain-barrier in TBI patients. CSF BNP concentrations are elevated and peak on day 3 after moderate to severe TBI. CSF BNP may originate from the brain and may be a potential biomarker of TBI.

Experimental model of congestive heart failure induced by transverse aortic constriction in BALB/c mice

IntroductionMurine transverse aortic constriction (TAC) is a frequently used model of pressure overload-induced left ventricular (LV) remodeling. However, there is considerable variability in disease progression to overt heart failure (HF) development in the most commonly used strain of mice (i.e., C57BL/6J). Studies have shown that C57BL/6J mice are more resistant than BALB/c mice to congestive HF development following myocardial infarction or angiotensin II-induced hypertension. Therefore, we tested the hypothesis that BALB/c mice may be a better research model to study TAC-induced progressive HF. MethodsFollowing sham or TAC surgery in both C57BL/6J (n = 29) and BALB/c (n = 32) mice, we evaluated cardiac dimensions and function by echocardiography at 2, 4, 8, and 12 weeks and monitored survival throughout the study. In a separate cohort of BALB/c mice, we repeated the study in the presence of the angiotensin converting enzyme inhibitor enalapril or a vehicle initiated 2 weeks post-TAC and administered for 6 weeks. At the end of the studies, we assessed the heart weight, lung weight, and plasma brain natriuretic peptide (BNP) concentration. ResultsFollowing comparable TAC, both C57BL/6J and BALB/c mice showed significant LV remodeling compared with the sham control mice. BALB/c mice progressively developed systolic dysfunction, LV dilation, lung congestion, and significant mortality, whereas C57BL/6J mice did not. In the separate cohort of BALB/c TAC mice, enalapril significantly reduced the heart weight, lung weight, and plasma BNP concentration and improved survival compared with the vehicle control. DiscussionBALB/c mice uniformly developed congestive HF post-TAC. Enalapril was effective in improving survival and reducing lung congestion in this model. The data suggest that BALB/c mice may be a better research tool than C57BL/6J mice to study TAC-induced disease progression to HF and to evaluate novel therapies for the treatment of chronic HF with reduced ejection fraction.

The diagnostic value of brain natriuretic peptide in men with comorbid essential arterial hypertension and type 2 diabetes mellitus

The aim of the work is to investigate the diagnostic informativeness of brain natriuretic peptide (BNP) in men with left ventricular (LV) diastolic dysfunction (DD) and initial stages of chronic heart failure (CHF) in comorbid stage 2 essential hypertension (EH 2) and type 2 diabetes mellitus (T2DM).Materials and methods. We examined 211 men. 79 people without signs of cardiovascular disease were assigned to a control group. 62 patients with EH 2 and CHF no higher than NYHA functional class (FC) I were included in the 1st, and 70 men with EH 2 combined with T2DM and CHF FC I–II formed the 2nd main study group. The plasma concentration of BNP was measured by ELISA. The examination included the determination of HbA1c, blood lipid profile, echocardiography. The mathematical processing was performed using the standard statistical package Statistica 6.1.Results. Plasma levels of BNP in comorbid EH 2 and T2DM were significantly higher (102.18 ± 4.18 pg/ml) than those in patients with EH without T2DM (77.40 ± 2.85 pg/ml) and in subjects without cardiovascular diseases (21.74 ± 0.59 pg/ml) (P &lt; 0.00001). According to the regression analysis, the level of BNP was associated with changes in parameters of intracardiac hemodynamics in patients with EH2. In patients with comorbid EH 2 and T2DM, the level of BNP was also associated with indicators of systemic hemodynamics and body weight. BNP as a marker of CHF at the recommended borderline level (35 pg/ml) in patients with EH 2 and T2DM was characterized by a sensitivity of 98.57 % and specificity of 55.32 %. The BNP borderline levels with higher specificity were determined for early diagnosis of CHF in EH 2 with T2DM and obesity comorbidities.Conclusions. BNP, as an early marker of LV DD and the initial stages of CHF at the recommended borderline level in men with comorbid EH 2 and T2DM does not have sufficiently high specificity. In these pathological conditions, the determined borderline levels of BNP can be used as indicative surrogate markers for early diagnosis of CHF during screening with the view to identify persons for further echocardiographic additional examination and in cases where echocardiography is not possible.

The role of the brain natriuretic peptide gene polymorphism in the diagnostic use of the biomarker in myocardial dysfunction in men, residents of Podillya with comorbid essential hypertension and type 2 diabetes mellitus

There is a growing interest in the early detection of signs of myocardial dysfunction, especially in comorbid patients for timely prevention of progression of disease, reducing the risk of complications, improving their quality of life. The aim of the work was to optimize the diagnosis of myocardial dysfunction in men, residents of Podillya, taking into account the plasma concentration of brain natriuretic peptide (BNP) and polymorphism of the corresponding gene under conditions of comorbidity of essential hypertension (EH) with left ventricular hypertrophy (LVH) and type 2 diabetes mellitus (T2D). We examined 211 men: 79 persons without the signs of cardiovascular diseases, 62 patients with EH 2 and chronic heart failure (CHF) 0-I functional classes (FC) according to NYHA Classification and 70 – with EH 2 combined with T2D and CHF FC I-II. The examination included the determination of plasma concentration of BNP, the brain natriuretic peptide gene polymorphism (polymorphic locus T-381C), indices of doppler-echocardiography. The mathematical processing was performed using the standard statistical package Statistica 10. During the study, we calculated the primary statistical indicators, identified differences between groups on statistical grounds, made correlation and discriminant analysis. Diastolic dysfunction (DD) of the left ventricle (LV) was diagnosed in 45.16% of patients in the group with EH 2, and 90% in the group of comorbid patients. It was determined that men, residents of Podillya, with presence and absence of T2D, have dominating T381C genotype of the BNP gene (p&gt;0.05). Lower plasma concentration of BNP that is peculiar for homozygous T381T genotype, in comparison with carriers of allele C of BNP gene and the average values of this biomarker in patients with DD may affect its informativeness in the diagnosis of myocardial dysfunction and requires a lower level of diagnosis. Appropriate borderline levels of BNP were determined for early diagnosis of DD in carriers of polymorphic variants of the BNP gene in men, residents of Podillya, with comorbid course of EH 2 and T2D. It is recommended to determine the genotype of the corresponding gene (polymorphic locus T-381C) and plasma level of BNP and focus on the calculated borderline levels of BNP to optimize the diagnosis of myocardial dysfunction in comorbid patients with EH 2 and T2D. For carriers of the T381T genotype it is ≥55.57 pg/ml, for carriers of the C allele (heterozygous T381C and homozygous C381C) of the BNP gene it is ≥69.13 pg/ml.

Systemic-to-Pulmonary Collateral Flow Correlates with Clinical Condition Late After the Fontan Procedure.

In the Fontan circulation, there is a substantial degree of systemic-to-pulmonary collateral flow (SPCF), which can be measured by cardiac magnetic resonance (CMR). However, the correlation between the degree of SPCF and long-term outcomes is not fully understood. We retrospectively studied 321 patients who underwent the Fontan procedure and CMR at a single center. Using CMR, we calculated SPCF as pulmonary blood flow - systemic blood flow. %SPCF was defined as SPCF ÷ pulmonary blood flow. The mean age of patients at CMR was 14.3 ± 7.5years. The average %SPCF was 13.0% ± 11.0%. With a multivariate analysis, %SPCF was significantly correlated with time (i.e., the longer the time period since the Fontan procedure, the lower the %SPCF) (p = 0.006), previous total anomalous pulmonary vein drainage (p = 0.007), a low pulmonary artery index (Nakata index) before the Fontan procedure (p = 0.04), and older age at the time of the Fontan procedure (p = 0.002). Regarding the findings after the Fontan procedure, %SPCF was significantly correlated with ventricular end-diastolic volume (p < 0.001), ventricular end-systolic volume (p < 0.001), central venous pressure (p < 0.001), plasma brain natriuretic peptide concentration (p < 0.001), hemoptysis (p = 0.009), and poor New York Heart Association functional class (p = 0.007). SPCF was correlated with clinical condition after the Fontan procedure. The importance of sufficient growth of the pulmonary vascular bed should be emphasized because the development of SPCF is believed to result from the poor condition of the pulmonary circulation.

A Randomized, Controlled Pharmacokinetic and Pharmacodynamics Trial of Ambrisentan After Fontan Surgery.

To determine the pharmacokinetics, pharmacodynamics, and safety of the hepatically metabolized endothelin receptor antagonist, ambrisentan in children after Fontan surgery. Prospective, randomized, double-blind, placebo-controlled pharmacokinetic/pharmacodynamics and safety trial. Single-center, postoperative cardiac ICU. Children undergoing elective Fontan surgery. Subjects randomized on postoperative day number 1 to short-term (3 d) treatment with oral ambrisentan (2.5 mg in suspension, daily) versus placebo (4:1 randomization). Plasma drug concentrations were measured at 0.5, 1, 2, 4, and 18-36 hours after the first dose. We developed a population pharmacokinetic model in NONMEM 7.2 (Icon Solutions, Ellicott City, MD) and applied the model to dose-exposure simulations. Pharmacodynamics endpoints were assessed at baseline and 3 hours after study drug administration, using postoperative hemodynamic monitoring lines. The analysis included 16 patients, 13 on ambrisentan (77 plasma samples); median age 36 months (range, 26-72 mo), weight 13.3 kg (11.1-17.6 kg), and nine males. There were no differences in baseline characteristics between ambrisentan and controls. A one-compartment model with first-order absorption and lag-time characterized the data well. Allometrically scaled weight was the only covariate retained in the final model. Typical values for clearance and volume of distribution were lower than previously reported in adults, 1 L/hr/70 kg and 13.7 L/70 kg, respectively. Simulated exposures with doses of 0.1-0.2 mg/kg approximated therapeutic exposures in adults with pulmonary arterial hypertension receiving 5 mg or 10 mg doses. Ambrisentan lowered plasma brain natriuretic peptide concentrations (452 ± 479 to 413 ± 462; p = 0.046), Fontan pressures (16.8 ± 2.9 to 15.6 ± 2.9; p = 0.01), and indexed pulmonary vascular resistance (2.3 ± 0.9 to 1.8 ± 0.6; p = 0.01) with no drug-related adverse events. Ambrisentan clearance is reduced following Fontan surgery, perhaps reflecting abnormal hepatic metabolism in this population. The observed safety profile appears favorable and hemodynamic effects of ambrisentan may be beneficial for Fontan patients.

The value of B-type natriuretic peptide plasma concentrations in very old people with chronic peripheral oedema

Chronic peripheral oedema is frequent in old patients, and very often results from multiple causes. To investigate whether determination of B-type natriuretic peptide plasma concentration helps with the diagnosis of chronic peripheral oedema aetiologies. This was a cross-sectional observational study conducted in geriatric hospital wards (intermediate and long-term care) on consecutive in-hospital patients aged>75 years with chronic peripheral oedema and no dyspnoea. From medical history, physical examination, routine biological tests and chest radiography, two investigators determined the aetiologies of oedema, with special attention paid to recognizing chronic heart failure. This reference diagnosis was compared with the clinical diagnosis mentioned in the medical chart. Brain natriuretic peptide plasma concentrations were measured soon after the investigators' visit. Among the 141 patients (113 women and 28 men) aged 86±6 years, a single aetiology was identified in 53 (38%), and multiple aetiologies in 84 (60%). The main aetiologies were venous insufficiency (69%), chronic heart failure (43%), hypoproteinaemia (38%) and drug-induced oedema (26%). Chronic heart failure was frequently misdiagnosed by attending clinicians (missed in 18 cases and wrongly diagnosed in 14 cases). Brain natriuretic peptide concentration was significantly higher in patients with chronic heart failure than in those without: median (interquartile range) 490 (324-954) versus 137 (79-203) pg/mL, respectively (P<0.0001). The receiver operating characteristic curve showed that a concentration of 274pg/mL was appropriate for diagnosing chronic heart failure, with a specificity of 0.89 and a sensitivity of 0.82. Brain natriuretic peptide concentrations above this cut-off were significantly and independently associated with the diagnosis of chronic heart failure. Chronic heart failure is frequently misdiagnosed in old patients with chronic peripheral oedema, and B-type natriuretic peptide plasma concentration helped to improve the diagnosis of this condition and identify chronic heart failure.

Association of Plasma Renalase and Left Ventricle Mass Index in Heart Failure Patients Stratified to the Category of the Ejection Fraction: A Pilot Study.

Heart failure represents a growing health problem, with increasing morbidity and mortality globally. According to the mechanisms involved in the pathogenesis of heart failure, many biomarkers have been proposed for the timely diagnosis and prognostication of patients with heart failure, but other than natriuretic peptides, none of them has gained enough clinical significance. Renalase, a new protein derived from kidneys was demonstrated to metabolize catecholamines and to have a cardioprotective role. The aim of the study was to determine whether renalase and brain natriuretic peptide (BNP) concentration could be used to differentiate heart failure patients stratified to the category of the ejection fraction and whether plasma renalase could be used as a biomarker for left ventricle hypertrophy in all subgroups of heart failure patients. We included patients diagnosed with heart failure and stratified them to the three subgroups according to the ejection fraction. Regarding echocardiographic parameters, HFmrEF had an intermediate profile in between HFrEF and HFpEF, with statistical significance in most evaluated parameters. BNP concentration was significantly different in all three subgroups (p < 0.001), and renalase was statistically higher in HFrEF (p = 0.007) compared to the HFmrEF and HFpEF, where its results were similar, without statistical significance. Renalase plasma concentration was demonstrated to be highly and positively associated with left ventricle mass index in HFrEF (p = 0.029), as well as increased plasma concentration of BNP (p = 0.006). In the HFmrEF group of patients, body mass index was positively associated with LVMI (p = 0.05), while in the patients with HFpEF, diabetes mellitus was demonstrated to have a positive association with LVMI (p = 0.043). These findings suggest that renalase concentration may be measured in order to differentiate patients with reduced ejection fraction. Plasma renalase concentrations positively correlated with left ventricle hypertrophy in patients with reduced ejection fraction, being strongly associated with increased left ventricular mass index.

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.

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.

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.

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.