Brain Natriuretic Peptide Concentrations Research Articles

Fluorescent aptasensor based on competitive recognition strategies and point-of-care testing system for brain natriuretic peptide detection

Brain natriuretic peptide (BNP) is the preferred biomarker for clinical analysis, widely used in early screening and prognostic monitoring of cardiovascular and neurological diseases. Due to the low concentration and short half-life of BNP in the blood, its sensitive detection remains a challenge that must be overcome. With the rapid development of molecular diagnosis and point-of-care testing (POCT), developing a BNP biosensor with high sensitivity, good stability, accuracy, speed, and low-cost is of great significance for clinical applications and emergency diagnosis. However, BNP in human blood exists in various forms, and traditional fluorescence sensors may lead to overestimation of the concentration. In this work, we constructed an “on” fluorescent aptasensor based on competitive recognition strategy for quantitative detection of BNP, and built a fluorescence sensing detection system based on smartphone to achieve rapid on-site detection. We designed a specific aptamer labeled with carboxyfluorescein (FAM) with a simple structure and high biological affinity for selective capture of BNP, and utilized the large specific surface area and excellent fluorescence quenching effect of carboxylated graphene oxide (GO-COOH) as a carrier and quencher for the aptasensor. By optimizing experimental parameters such as aptamer and GO-COOH concentrations, as well as quenching/recovery time, linear sensitive detection of BNP was achieved in the concentration range of 0.01 ng/mL–10 ng/mL, with a detection limit as low as 10 pg/mL, good specificity, and excellent application potential in artificial serum spiking experiments. Additionally, a stable and sensitive fluorescence signal collection system has been developed to meet the needs of portable detection, breaking through the usage environment of traditional fluorescence detection equipment and filling the gap of portable fluorescence biosensing. In summary, we have creatively proposed a fluorescent aptasensor that enables rapid and sensitive detection of BNP and the development of low-cost fluorescent biosensors. The combination with POCT has shown broad application prospects and also provides some ideas for the fluorescence detection of other protein biomarkers.

A novel electrochemical immunosensor based on AuNPs/PNR/CS@MWCNTs-COOH for rapid detecting warning markers-BNP of heart failure caused by myocardial infarction

Heart failure (HF) is an insidious and dangerous disease that significantly impairs a patient’s quality of life and safety. It is not easy to detect in mild cases, and once it progresses to severe stages, deterioration can be rapid and challenging to reverse. Currently, early warning and prognostic risk assessment technologies are lacking, and there is an urgent need for precise early warning, risk assessment and diagnosis and treatment of HF at the cellular or molecular level. In this study, an electrochemical immunosensor based on AuNPs/PNR/CS@MWCNTs-COOH was prepared to detect brain natriuretic peptide (BNP), a biomarker for early warning of HF caused by myocardial infarction. Among them, the CS@MWCNTs-COOH nanocomposites and the polymerized neutral red (PNR) films on the electrode surface effectively enhanced the conductivity of the modified electrodes and significantly increased the specific surface area through the formation of three-dimensional nanostructures. AuNPs loaded on PNR/CS@MWCNTs-COOH provided a stable gold-ammonia bond for the specific antibody loading of BNP, facilitating the development of an electrochemical immunosensor with high selectivity for BNP detection. Furthermore, this work used cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) to improve aspects that influence the immunosensor’s analytical performance. Under ideal conditions, the immunosensor was tested for immunological qualities using differential pulse voltammetry (DPV), resulting in sensitive measurement of BNP concentration in undiluted serum samples.The peak current Ip of the response signal is linearly proportional to the LgCBNP in the range of 1.95 × 10−3 ng mL−1 to 8.0 ng mL−1, with a detection limit of 0.80 × 10−3 ng mL−1 (S/N=3). It can achieve highly sensitive identification and detection of trace BNP in complex biological samples and provide a convenient and efficient method for HF-related marker detection. Furthermore, it also can serve as a scientific basis and a new method for the development of early warning technology for HF and related pathological mechanism research.

Diagnostic utility of velocity ratio for paradoxical low-flow/low-gradient aortic stenosis.

Calcification score by cardiac computed tomography (CT) is required for diagnosis of paradoxical low-flow/low-gradient (PLFLG) aortic stenosis (AS). According to the guideline, velocity ratio (VR) < 0.25 by echocardiography is defined as severe AS, but utility of VR in patients with PLFLG AS remains unknown. This retrospective study was therefore conducted to investigate the utility of VR for a diagnosis of severe AS based on CT in patients with PLFLG AS. We studied 58 patients with PLFLG AS. Severity of AS was defined as calcium score derived from cardiac CT. Of the 58 patients, 28 (48.3%) were diagnosed with severe AS based on CT, while 23 of them (82.1%) had VR < 0.25. It was noteworthy that receiver operating characteristic curve analysis showed that the optimal VR cutoff value for a diagnosis of severe AS was 0.25, with an area under the curve of 0.870 (P < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of VR < 0.25 for a diagnosis of severe AS were 82.1%, 86.7%, 85.2% and 83.9%, respectively. Furthermore, patients who match the value of VR and severity of AS based on CT had higher prevalence of atrial fibrillation, higher serum brain natriuretic peptide concentration, larger left ventricular end-diastolic volume, and left ventricular stroke volume index. The measurement of VR is simple, and VR < 0.25 can be used for diagnosis of patients with PLFLG AS as severe. Our findings may thus have clinical implications for routine clinical practice.

High plasma BNP concentration associates with clinical outcome after mechanical thrombectomy: Post hoc analysis of SKIP

ObjectivesHeart failure may result in reduced brain perfusion, limiting the blood flow needed to achieve clinical recovery. We investigated whether plasma levels of brain natriuretic peptide (BNP), a biological marker of heart failure, were related to clinical outcomes after mechanical thrombectomy (MT). Materials and MethodsData were analyzed from stroke patients with internal carotid or middle cerebral artery occlusion enrolled in the SKIP trial for whom plasma level of BNP was evaluated on admission. Favorable outcome was defined as a modified Rankin scale score of 0–2 at 3 months. ResultsAmong 169 patients (median age, 74 years; 62% men, median National Institutes of Health Stroke Scale score, 18), 104 (62%) achieved favorable outcomes. Median plasma BNP level was lower in the favorable outcome group (124.1 pg/mL; interquartile range [IQR], 62.1–215.5 pg/mL) than in the unfavorable outcome group (198.0 pg/mL; IQR, 74.8–334.0 pg/mL; p=0.005). In multivariate regression analysis, the adjusted odds ratio for BNP for favorable outcomes was 0.971 (95% confidence interval, 0.993–0.999; p=0.048). At 3 months after onset, the favorable outcome rate was lower in the ≥186 pg/mL group (45%) than in the <186 pg/mL group (72%; p=0.001). This significant difference remained regardless of the presence of atrial fibrillation (AF), with rates of 47% and 76%, respectively, in AF patients (p=0.003) and 33% and 68%, respectively, in patients without AF (p=0.046). ConclusionHigh plasma BNP concentration appears associated with unfavorable outcomes after MT.

КАРДИОМЕТАБОЛИЧЕСКИЙ ПРОФИЛЬ С УЧЕТОМ СТАДИРОВАНИЯ ПО CMDS У ЛИЦ МОЛОДОГО ВОЗРАСТА

Abstract. Introduction. The burden of cardiovascular disease, diabetes mellitus, and the associated mortality remains high. One classification system that predicts the development of cardiovascular events and type 2 diabetes mellitus is Cardiometabolic Disease Staging (CMDS). The study of new cardiometabolic profile parameters is relevant in the context of their association with residual cardiovascular risk. The aim of the study was to evaluate the cardiometabolic profile, including extended parameters, in young adults, while taking into account the CMDS. Materials and Methods. 185 male and female subjects aged 35.0 [30.0–39.0] years were examined. The participants were divided into groups according to the CMDS classification: Stage 0, metabolically healthy; Stage 1 (low risk), one or two risk factors (RFs) other than prediabetes; Stage 2 (intermediate risk), presence of ≥3 risk factors or prediabetes; Stage 3 (high risk), presence of ≥3 risk factors and prediabetes. The study examined visceral adiposity index, visceral fat level, insulin resistance, leptinemia, hyperuricemia, glomerular filtration rate, C–reactive protein, and N–terminal brain natriuretic peptide concentrations. The data were processed in SPSS Statistics 26. Results and Discussion. The cardiometabolic profile demonstrated unfavorable alterations with the progression of CMDS stages. Across the spectrum from CMDS 0 to CMDS 3, we observed a significant rise in the prevalence of abdominal obesity (0% to 100%, p&lt;0,001), body mass index ≥25 kg/m2 (16.2% to 100%, p&lt;0.001), and excess visceral fat level (0% to 23.8%, p&lt;0.001). Simultaneously, the prevalence of hypercholesterolemia demonstrated a significant rise (24.3% to 52.4%, p=0.025), as did elevated low–density lipoprotein cholesterol (32.4% to 76.1%, p=0.014), insulin resistance (2.7% to 66.7%, p&lt;0.001), leptinemia (45.9% to 90.5%, p=0.009), C–reactive protein (2.7% to 57.1%, p&lt;0.001) and hyperuricemia (16.2% to 61.9%, p&lt;0.001). The median values of these parameters also increased. Conclusions. Our data confirm the simultaneous increase in both the quantity and intensity of risk factors, manifestations of adiposopathy associated with increasing residual cardiovascular risk. Our results substantiate the feasibility of using the CMDS classification at the stage of primary prevention of cardiometabolic diseases to identify groups with the most significant metabolism disorders of lipid, carbohydrate and purine metabolism in young adults.

Comparing Left Bundle Branch Area vs Right-Ventricular Septal Pacing in High-Degree Conduction Disease After Transcatheter Aortic Valve Replacement: Randomized Trial Study Protocol

Left bundle branch area pacing (LBBAP) is a novel method of conduction-system pacing in the muscular interventricular septum. Although LBBAP has been shown to produce physiologic electrical and mechanical intraventricular synchrony, superiority of LBBAP, compared to right ventricular septal pacing (RVSP) at preserving normal left-ventricular (LV) systolic function after transcatheter aortic valve replacement (TAVR) has not been demonstrated. Left Bundle BRAVE is an investigator-initiated, multicentre, prospective, double-blinded, randomized, crossover study investigating the superiority of LBBAP, compared to RVSP, with respect to preservation of systolic function in patients with high-degree conduction disease after TAVR. Adults with severe aortic stenosis and normal systolic function who sustain high-grade atrioventricular block within 4 weeks of TAVR are eligible. All subjects receive a biventricular pacemaker generator with RVSP, and LBBAP leads. Participants are randomly assigned to 9 months of each pacing mode, in series. The primary endpoint is change in global longitudinal strain, tested in series with change in LV ejection fraction, comparing RVSP to LBBAP. Secondary endpoints include the following: echocardiographic markers of interventricular synchrony and right ventricular performance; heart failure functional status and symptom classification; 6-minute walk test results; pacemaker and lead performance; and brain natriuretic peptide concentration. The Left Bundle BRAVE study is designed to identify an upstream and clinically relevant marker of superiority in LBBAP, compared to RVSP, at preventing deterioration of LV function in patients with a high ventricular pacing burden after TAVR. ClinicalTrials.gov identifierNCT05541679

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.

The Influence of Increased Concentrations of Brain Natriuretic Peptide on the Level of Hemodynamic Reactions in Individuals Living and Working in the European North and the Arctic of the Russian Federation

The Influence of Increased Concentrations of Brain Natriuretic Peptide on the Level of Hemodynamic Reactions in Individuals Living and Working in the European North and the Arctic of the Russian Federation

Risk assessment according to the presence of left heart disease phenotype in pulmonary arterial hypertension patients: a multicenter cohort study

Abstract Introduction Subclinical left heart disease (LHD) may impact the management of pulmonary arterial hypertension (PAH) [1]. Purpose To evaluate the influence of a LHD phenotype on PAH risk stratification. Methods We retrospectively reviewed the data of consecutive PAH patients followed at 7 tertiary centers from 2001 to 2021, and selected those with all parameters available to determine risk of death by means of the COMPERA and COMPERA 2.0 scores, both at baseline and at the first disease reassessment including right heart catheterization. These subjects were classified as no-LHD or LHD according to the AMBITION trial criteria, i.e. absence or presence, respectively, of ≥ 3 among body mass index ≥ 30 kg/m2, systemic hypertension, diabetes mellitus, and coronary artery disease; and/or pulmonary vascular resistance between 3 and 3.75 WU or between 3.75 and 6.25 WU together with pulmonary artery wedge pressure (PAWP) between 13 and 15 mmHg [2,3]. The characteristics between the 2 groups were compared by chi-square test, T-test, or Mann-Whitney test, and Kaplan-Meier curves for overall survival by log-rank test. Results Of 286 patients included in the analysis, 57 (20%) had a LHD phenotype. The first complete reassessment was performed 7 ± 5 months after baseline. Compared with no-LHD, subjects with LHD were older, had more often cardiovascular comorbidities, and had higher E/e’ ratio, left atrial area and PAWP, but had lower brain natriuretic peptide concentrations and better right ventricular function and pulmonary hemodynamics (Figure 1). They were also less commonly treated with phosphodiesterase inhibitors or riociguat (54% vs 70%, P=0.03) and dual oral therapy (26% vs 43%, P=0.03), while they used more beta-blockers (47% vs 16%, P&amp;lt;0.001) and ACE inhibitors or angiotensin receptor blockers (40% vs 21%, P=0.004). At baseline, the proportion of patients with low vs high risk was greater in LHD than in no-LHD with COMPERA, but not with COMPERA 2.0. Moreover, risk profile significantly improved during follow-up only in no-LHD with COMPERA, but in both groups with COMPERA 2.0 (Figure 1). While all-cause mortality was significantly different across baseline COMPERA and COMPERA 2.0 risk strata in no-LHD, either approach for risk stratification failed to discriminate LHD subgroups with different prognosis (Figure 2). However, both COMPERA and COMPERA 2.0 risk categories differentiated mortality in LHD at the first disease reassessment (log-rank P &amp;lt;0.001, not shown). Conclusions This study suggests that the performance of risk stratification scores COMPERA and COMPERA 2.0 in PAH subjects with a LHD phenotype is limited, although the former may retain value during follow-up. Alternative tools may be needed for prognostication in this patient subset.

Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy.

Our objective was to evaluate the long-term prognostic value of high-sensitivity cardiac troponin-I (hs-cTn-I) in idiopathic dilated cardiomyopathy (DCM). First, patients were divided into an end-event group (n = 55) and a non-end-event group (n = 67). Then, patients were included in the subgroup analysis to compare the diagnostic value of brain natriuretic peptide (BNP) and hs-cTn-I in different populations. hs-cTn-I and BNP concentrations were higher in the end-event group. The Cox regression analysis indicated that high hs-cTn-I was a risk factor for poor long-term prognosis. Receiver operating characteristic analysis showed that the area under the curve (AUC) for hs-cTn-I to predict end events was 0.751, and the AUC for BNP was 0.742. The correlation analysis suggested that hs-cTn-I was related to the percentage change in left ventricular internal diameter at end-diastolic and left ventricular ejection fraction. Subgroup analysis showed that compared with BNP, hs-cTn-I was more suitable for predicting end events in patients with preserved renal function (AUC: 0.853 vs 0.712, P = 0.04). In conclusion, hs-cTn-I is a potential biomarker for evaluating long-term prognosis in idiopathic DCM, and its predictive value is higher than that of BNP in patients with preserved renal function.

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.

ET-1 receptor type B (ETBR) overexpression associated with ICAM-1 downregulation leads to inflammatory attenuation in experimental autoimmune myocarditis.

An experimental autoimmune myocarditis rat model was established by subcutaneous injection of porcine myocardial myosin (PCM). The effect of ET-1 receptor type B (ETBR) overexpression on autoimmune myocarditis was observed via tail vein injection of ETBR overexpression lentivirus in rats. We further investigated the mechanisms involved in the regulation of autoimmune myocarditis by ETBR overexpression. Six rats were randomly selected from 24 male Lewis rats as the NC group, and the remaining 18 rats were injected with PCM on Day 0 and Day 7, to establish the experimental autoimmune myocarditis (EAM) rat model. The 18 rats initially immunized were randomly divided into three groups: the EAM group, ETBR-oe group, and GFP group. On Day 21 after the initial immunization of rats, cardiac echocardiography and serum brain natriuretic peptide (BNP) analysis were performed to evaluate cardiac function, myocardial tissue HE staining was performed to assess myocardial tissue inflammatory infiltration and the myocarditis score, and mRNA expression of IFN-γ, IL-12, and IL-17 was detected by qRT-PCR. Subsequently, immunohistochemical analysis was performed to detect the localization and expression of the ETBR and ICAM-1 proteins, and the expression of ETBR and ICAM-1 was verified by qRT-PCR and western blotting methods. On Day 21 after initial immunization, left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), and serum BNP concentrations increased in the hearts of rats in the EAM group compared with the NC group (P < 0.01), and ejection fraction (EF) and fractional shortening (FS) decreased compared with those of the normal control (NC) group (P < 0.01). LVEDd, LVEDs, and serum BNP concentrations decreased in the ETBR-oe group compared with the EAM group, while EF and FS increased significantly (P < 0.01). HE staining showed that a large number of inflammatory cell infiltrates, mainly lymphocytes, were observed in the EAM group, and the myocarditis score was significantly higher than that of the NC group (P < 0.01). Compared with that of the EAM group, myocardial tissue inflammatory cell infiltration was significantly reduced in the ETBR-oe group, and the myocarditis scores were significantly lower (P < 0.01). The mRNAs of the inflammatory factors IFN-γ, IL-12 and IL-17 in myocardial tissue of rats in the EAM group exhibited elevated levels compared with those of the NC group (P < 0.01) while the mRNAs of IFN-γ, IL-12 and IL-17 were significantly decreased in the ETBR-oe group compared with the EAM group (P < 0.01). Immunohistochemistry showed that the staining depth of ETBR protein in myocardial tissue was greater in the EAM group than in the NC group, and significantly greater in the ETBR-oe group than in the EAM group, while the staining depth of ICAM-1 was significantly greater in the EAM group than in the NC group, and significantly lower in the ETBR-oe group than in the EAM group. The ICAM-1 expression level was significantly higher in the EAM group than in the NC group (P < 0.01), and was significantly lower in the ETBR-oe groupthan in the EAM group (P < 0.01).

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.

The Predictive Value of Serum NT-proBNP on One-Year All-Cause Mortality in Geriatrics Hip Fracture: A Cohort Study.

Objective This study evaluated the association between N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and one-year mortality in geriatric patients with intertrochanteric and femoral neck fractures receiving the operative treatment. Methods Consecutive age ≥65 years patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. The multivariate logistic regression models were used to identify the association between preoperative NT-proBNP concentrations and mortality. All analyses were performed using EmpowerStats and the R software. Result One thousand two hundred nineteen patients were included in the study. The average age was 79.73±6.65 years (range 66-99 years). The mean NT-proBNP concentration was 616.09±1086.85 ng/L (median 313.40 ng/L, range 16.09-20123.00 ng/L). The follow-up was 35.39±15.09 months (median 35.78 months, range 0.10-80.14 months). One hundred and eleven (9.1%) patients died within one year. After adjusting for confounding factors, multivariate logistic regression models showed a curved association between preoperative NT-proBNP concentration and one-year mortality. When the NT-proBNP concentration was below 1099 ng/L, the mortality increased by 10% (OR=1.10, 95%CI: 1.03-1.17, P=0.0025) when NT-proBNP increased by 100 ng/L. When the NT-proBNP concentration was above 1099 ng/L, the mortality did not increase anymore when NT-proBNP increased (OR=1.00, 95%CI: 0.99-1.02, P=0. 7786). Thus, NT-proBNP was a valuable indicator to predict high one-year mortality in practice. Conclusion The NT-proBNP concentrations were nonlinearly associated with mortality in elderly hip fractures with a saturation effect, and NT-proBNP was a risk indicator of all-cause mortality. A well-designed controlled trial to show the role of mortality by decreasing the concentration of NT-proBNP is needed in the future.

СРАВНЕНИЕ ИНФОРМАТИВНОСТИ ОПРЕДЕЛЕНИЯ NT-PROBNP ПОЛУКОЛИЧЕСТВЕННЫМ И КОЛИЧЕСТВЕННЫМ МЕТОДАМИ ДЛЯ РАННЕЙ ДИАГНОСТИКИ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Вackground. Heart failure (HF) is one of the main causes of morbidity and mortality worldwide. Since it is important to diagnose CH early and quickly, at the outpatient appointment, there is a need to create and introduce into practice a portable highly sensitive method for the determination of BNP, NT-proBNP. Purpose of the study. To determine the possibility of using reagents for semi-quantitative determination of N-terminal brain natriuretic peptide antigen for early detection of heart failure. Methods of statistical analysis. Microsoft Office Excel 2019 program was used. Patient Characterization and Research Methods. An open cross-sectional non-randomized cohort study included 50 patients (mean age 63.5 years) who applied on an outpatient basis for consultation to a cardiologist. In addition to standard clinical, biochemical and instrumental examinations, the concentration of N-terminal brain natriuretic peptide (NT-proBNP) was determined by quantitative and semi-quantitative immunochromatographic method (LLC NPO "BioTest", Novosibirsk). The diagnosis of chronic heart failure (CHF) was established in accordance with national and European recommendations. Methods of statistical analysis. Microsoft Office Excel 2019 program was used. Results and conclusion. In the course of the study, it was found that semi-quantitative method is highly sensitive for detection of small NT-proBNP elevations, which is important for early diagnosis of heart failure, including subclinical forms. Semi-quantitative method also allows to distinguish a group of patients with high NT-proBNP values. The relationship of NT-proBNP level with the course and prognosis of CHF requires further study.

Investigation of the efficacy of the change ratio of brain natriuretic peptide for predicting the cardiac effects of chemoradiotherapy on esophageal cancer.

The aim of this study was to investigate the effectiveness of brain natriuretic peptide (BNP) as a predictor of radiological effects on the heart. A total of 41 patients with esophageal cancer who underwent chemoradiotherapy (CRT) were retrospectively investigated. The BNP levels were measured on the first day of CRT (pre-CRT) and the last day of CRT (post-CRT), and the median concentration of BNP and dosimetric parameters of the heart were calculated. The change ratio of BNP was calculated as follows: [(BNP post-CRT) - (BNP pre-CRT)]/(BNP pre-CRT). The comparison of BNP pre-CRT with post-CRT was performed using a Wilcoxon signed-rank test. The relationship between dosimetric parameters and change ratio was analyzed using Spearman's correlation coefficient. The median levels of BNP of pre-CRT and post-CRT were 10 and 22 pg/ml, respectively, and the difference was statistically significant (P<0.0001). Significant correlations (all P<0.05) were observed between the change ratio and mean dose, V5, V10, V20, and V30. Of the cohort, 14 patients developed acute-to-subacute cardiac events, such as pericardial effusion, cardiomegaly, acute exacerbation of chronic heart failure, and a decreased ejection fraction. The change ratios of BNP, V5, V10, V20, and V30 were significantly higher in patients who experienced cardiac events compared with those who did not. The results of this study showed that BNP measurement, particularly the change ratio of BNP pre- and post-CRT, may be a useful cardiac event predictor in addition to dosimetric parameters.

Impact of donor-specific anti-HLA antibody on cardiac hemodynamics and graft function 3 years after pediatric heart transplantation: First results from the CTOTC-09 multi-institutional study

The aim of this study (CTOTC-09) was to assess the impact of “preformed” (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation.

Resveratrol is an organic compound widely studied for its therapeutic uses. We investigated whether resveratrol exerts cardioprotective effects by inhibiting ferroptosis via the Sirt1/p53 pathway. A heart failure model was established by aortic coarctation in Sirt1 knockout mice. The superoxide dismutase (SOD), glutathione (GSH) levels and mitochondrial morphology in murine heart tissues were assessed at different time points to determine the role of ferroptosis in heart failure progression. The cardiac function of mice with heart failure was evaluated by determining the brain natriuretic peptide (BNP) and sST2 concentration and conducting echocardiography. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were transfected with the p53 K382R mutant and Sirt1 interference lentiviral vectors. Immunoprecipitation (IP) experiments were performed to investigate whether Sirt1 influences ferroptosis via p53 K382 acetylation and SLC7A11 expression modulation. Resveratrol improved cardiac function in mice and decelerated ferroptosis and fibrosis progression in heart failure. However, the ability of resveratrol to prevent ferroptosis and treat heart failure was lost after silencing Sirt1. Sirt1 reduced ferroptosis by diminishing the levels of p53 K382 acetylation, reducing the degradation of SLC7A11, and increasing the levels of GSH and glutathione peroxidase 4 (GPX4) in cells. In conclusion, by activating the Sirt1/p53 pathway in heart failure, resveratrol decreased the depletion of SLC7A11, inhibited ferroptosis, and improved cardiac function.

Abnormal plasma ceramides refine high-risk patients with worsening heart failure.

Worsening heart failure (WHF) is a heterogeneous clinical syndrome with poor prognosis. More effective risk stratification tools are required to identify high-risk patients. Evidence suggest that aberrant ceramide accumulation can be affected by heart failure risk factors and as a driver of tissue damage. We hypothesized that specific ceramide lengths and ratios serve as biomarkers for risk stratification in WHF patients by reflecting pathological changes of distinct organ dysfunctions. We measured seven plasma ceramides using liquid chromatography-mass spectrometry (LC-MS) in 1,558 patients, including 1,262 participants in retrospective discovery set and 296 WHF patients in prospective validation set in BIOMS-HF study (Registry Study of Biomarkers in Heart Failure). Univariable and multivariable logistic regression models were constructed to identify associations of ceramides with organ dysfunctions. We constructed three ceramide-based scores linked independently to heart, liver, and kidney dysfunction, with ceramides and ratios included in each score specifying systemic inflammation, chronic metabolic disorder, and water-sodium retention. The combined ceramide heart failure score (CHFS) was independently associated with adverse outcomes [Hazard Ratio, 2.80 (95% CI: 1.78-4.40; P < 0.001); 2.68 995% CI: 1.12-6.46; P = 0.028)] and improved the predictive value of Acute Decompensated Heart Failure National Registry score and BNP [net reclassification index, 0.34 (95% confidence interval, CI: 0.19-0.50); 0.42 (95% CI: 0.13-0.70)] in the discovery and validation set, respectively. Lower BNP levels, but higher CHFS had the highest hazard of future adverse events in WHF patients. Abnormal plasma ceramides, associated with heart and peripheral organ dysfunctions, provide incremental prognostic information over the ADHERE score and brain natriuretic peptide concentration for risk stratification in WHF patients. This may facilitate the reclassification of high-risk patients in need of aggressive therapeutic interventions.

Assessing the significance of some biomarkers in perioperative period after thoracic aortic reconstruction

Aim. This study aims to assess the association between levels of biomarkers and postoperative complications in patients after thoracic and thoracoabdominal aortic reconstruction.Material and methods. This study included 132 patients. The most of them underwent ascending aortic and aortic arch reconstruction (65 and 57, respectively).The concentrations of proadrenomedullin, presepsin, procalcitonin, troponin I and N-terminal brain natriuretic peptide were measured before induction anesthesia, at the end of the surgical operation and in 6 hours after surgery.Results. 69 patients had postoperative complications. Among them, inflammatory (27,3%) and cardiovascular complications (12,1%) prevailed. At the end of the surgical operation, the levels of the biomarkers in patients without postoperative complications and with postoperative complications were for presepsin 326 [206; 451] и 620 [332; 829] p&lt;0,00001, tropononin I 0,77 [0,46; 1,39] and 1,49 [0,59; 3,39], p=0,01, proadrenomedullin 0,894 [0,683; 1,221] and 1,201 [0,944; 1,762], p=0,0002, procalcitonin 0,206 [0,147; 0,452] and 0,563 [0,307; 2,107], p=0,0002, respectively. According to log-linear regression model, the level of prepepsin at the end of the surgical operation &gt;459,5 (odds ratio (OR) 6,84, 95% confidence interval (CI): 3,14-14,87) or proadrenomedullin &gt;0,788 (OR 5,47, 95% CI: 1,52-19,68) are associated with the increased risk of postoperative complications. The level of presepsin &gt;519,5 pg/ml at the end of the surgical operation (OR 4,55, 95% CI: 1,97-10,47) is associated with the increased risk of inflammatory complications. Regarding the prognosis of the risk of prolonged cardiotonic drug infusions, threshold values for troponin were &gt;1,04 at the end of the surgical operation (sensitivity 75%, specificity 71,3%, AUC 0,785), &gt;1,57 in 6 hours after surgery (sensitivity 81,3%, specificity 71,6%, AUC 0,794).Conclusion. High levels of presepsin at the end of the surgical operation may be useful to predict the postoperative complications in patients who underwent the aortic surgery however, the low levels of presepsin do not exclude the development of postoperative complications. The increased level of troponin I at the end of the surgical operation and in 6 hours after surgery can be a predictor of the need for cardiotonic support in the postoperative period.