N-terminal Pro-brain Natriuretic Peptide Concentrations Research Articles

Efficacy and limitation of nonparoxysmal atrial fibrillation ablation in patients with heart failure with preserved ejection fraction.

Catheter ablation for atrial fibrillation (AF) reduces heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). However, the long-term outcomes and subclinical HF after nonparoxysmal AF ablation in HFpEF patients have not been fully evaluated. One-hundred-ninety nonparoxysmal AF patients with left ventricular ejection fraction ≥50% who underwent first-time AF ablation were studied. HFpEF was diagnosed from a history of congestive HF and/or combined criteria of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and transthoracic echocardiogram parameters, including average septal-lateral E/e' and tricuspid regurgitation peak velocity. Ninety-five patients with HFpEF (HFpEF group) were compared with 95 patients without HF (CNT group). Low voltage area (LVA) was defined as an area with a bipolar electrogram of <0.5 mV covering >5% of the total left atrial surface. The primary endpoint was a composite of death from any cause or hospitalization for worsening HF. The secondary endpoint was subclinical HFpEF defined from NT-proBNP concentration and average septal-lateral E/e' or tricuspid regurgitation peak velocity at 6-12 months after the procedure irrespective of the rhythm. Kaplan-Meier curves showed that the primary composite endpoint did not differ between the two groups (mean follow-up period 707 ± 75 days, log-rank p = 0.5330). However, significantly more patients in the HFpEF group reached the secondary endpoint (42 [44%] vs. 13 [14%], p < 0.0001). Multivariate analysis revealed that a high preablation NT-proBNP (odds ratio [OR] 1.001, 95% confidence interval [CI] 1.001-1.002, p = 0.0040) and the existence of LVA (OR 5.983, 95% CI 1.463-31.768, p = 0.0194) independently predicted the secondary endpoint in HFpEF patients. After nonparoxysmal AF ablation, mortality of HFpEF patients was not inferior compared to patients without coexisting HF. However, subclinical HF occasionally persisted especially in HFpEF patients with a high preprocedure NT-proBNP concentration and LVA.

Assessment of Specific Biomarkers' Profile and Structural, Functional Parameters of the Left Ventricle in Patients With Lymphomas Undergoing Antitumor Therapy.

To evaluate the dynamics of specific biomarkers for cardiotoxicity, endothelial dysfunction, fibrosis, systemic inflammation, and morpho-functional alterations in the left ventricular (LV) myocardium in patients with newly diagnosed lymphomas during 6 courses of polychemotherapy (PCT). The study included 30 patients with newly diagnosed lymphomas. All patients were evaluated for laboratory markers of cardiotoxicity at baseline and after 6 courses of chemotherapy (6 months), including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), endothelin-1 (ET-1), circulating cardiac biomarker ST-2, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and LV structural and functional echocardiographic (EchoCG) parameters. The changes in NT-proBNP and hsTnI concentrations during 6 courses of PCT were not statistically significant. Comparison of the baseline values with those after 6 courses of PCT showed increases in the median concentrations of ET-1 (3.38 and 5.5 pg/ml, respectively; p=0.438) and ST-2 (12.21 and 26.75 ng/ml, respectively; p=0.687). Markers of systemic inflammation were significantly decreased after 6 courses of PCT: the median CRP decreased from 15.2 to 0.72 mg/ml (p=0.006), and the median IL-6 decreased from 12.2 to 5.1 pg/ml (p=0.034). EchoCG data revealed a statistically significant impairment of the LV diastolic function parameters (E/A; E/e' lateral; E/e' average; left atrial volume index; isovolumic relaxation time). A moderate direct correlation was found between the ET-1 concentration and the isovolumic relaxation time at baseline and after 6 courses of PCT, respectively (r1 = 0.387, p=0.047 and r2 = 0.391, p=0.035). No changes in the LV systolic function were observed. The study showed that patients with lymphoproliferative diseases had no signs of cardiotoxicity during PCT according to the accepted criteria. This study described and highlighted for the first time the interrelation of endothelial dysfunction, profibrotic status, and LV diastolic dysfunction as manifestations of cardiovascular toxicity in patients with lymphoproliferative diseases. It is advisable to supplement the integrated strategies for the prevention and monitoring of PCT cardiovascular toxicity with a thorough evaluation of instrumental parameters of diastolic dysfunction for timely initiation/correction of cardioprotective therapy.

Plasma N-terminal pro-brain natriuretic peptide concentrations may help to identify patients with very low-risk acute pulmonary embolism: A preliminary study.

Patients with an acute pulmonary embolism (APE) are a heterogeneous group, and some of them may benefit from early discharge and an ambulatory care referral. We aimed to evaluate the use of N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma level assessment in patients with low-risk APE based on clinical findings (0 points on the simplified Pulmonary Embolism Severity Index (sPESI)). Preliminary analysis of an ongoing prospective study including 1,151 normotensive patients with at least a segmental APE. In the final analysis, 348 patients with a 0-point sPESI were included. Blood samples were collected within the first 24 h of admission. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis in patients with clinical deterioration. Clinical endpoints occurred in 3 patients who had higher plasma NT-proBNP levels than study participants with a favorable clinical course (164 [64-650] pg/mL compared to 2,930 [2,285.5-13,965] pg/mL; p = 0.01). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) for NT-proBNP for the prediction of the CEs was 0.918 (95% confidence interval [95% CI]: 0.831-1.00; p = 0.013). We defined the cutoff value of NT-proBNP at ≥1,641 pg/mL. Among subjects with 0 points on the sPESI, those with concentrations of NT-proBNP exceeding 1,641 pg/mL might require closer attention; remaining patients could be considered candidates for outpatient treatment. However, these findings warrant further investigation in a large, prospective group of patients.

Analysis of ultrasound coronary parameters and blood red cell distribution width and N-terminal pro-brain natriuretic peptide concentrations following coronary lesions in children with Kawasaki disease.

Aims/Background Kawasaki disease is an acute inflammatory condition primarily affecting the young children. It can lead to coronary artery abnormalities, which can worsen the prognosis. Early diagnosis of coronary disease is crucial for the effective treatment and the prognosis evaluation. To explore the clinical significance of ultrasound examination characteristics, peripheral blood red cell distribution width, and changes in N-terminal pro-brain natriuretic peptide levels for the early detect coronary artery abnormality in children with Kawasaki disease. Methods The case-control study was conducted. 85 Kawasaki disease patients diagnosed in our hospital from January 2020 to December 2023 were selected as the Kawasaki disease group. 100 healthy children who received physical examination in the Department of Child Healthcare during the same period were selected as control group. The cardiac ultrasound indicators, erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, N-terminal pro-brain natriuretic peptide of two groups were compared. The Kawasaki disease group was further divided into the coronary artery lesion group and the non-coronary artery lesion group based on whether coronary artery lesions occurred in the Kawasaki disease patients. The differences of above indicators were compared. Results The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of the Kawasaki disease group were all higher than those of the control group (p < 0.05). There was no significant difference in left ventricular ejection fraction between Kawasaki disease group and control group (p > 0.05). The erythrocyte sedimentation rate, C-reactive protein, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease group were all higher than those of control group (p < 0.05). The left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions (p < 0.05). The left ventricular ejection fraction of Kawasaki disease patients with coronary artery lesions was lower than that of Kawasaki disease patients without coronary artery lesions (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with coronary artery lesions were all higher than those of Kawasaki disease patients without coronary artery lesions, and the differences were statistically significant (p < 0.05). After treatment, the left main coronary artery, left anterior descending branch, and right coronary artery Z-scores of Kawasaki disease patients with coronary artery lesions significantly decreased (p < 0.05), and the left ventricular ejection fraction significantly increased (p < 0.05). The erythrocyte sedimentation rate, C-reactive protein, white blood cell, neutrophil percentage, platelet count, D-dimer, red cell distribution width, and N-terminal pro-brain natriuretic peptide of Kawasaki disease patients with or without coronary artery lesions significantly decreased after treatment compared with before treatment in the same group (p < 0.05). Conclusion Kawasaki disease patients with coronary artery lesions exhibit significantly increased coronary artery vessel diameter, as well as elevated red cell distribution width and N-terminal pro-brain natriuretic peptide concentration. The combined use of ultrasound combined with red cell distribution width and N-terminal pro-brain natriuretic peptide examination can assist in determining whether Kawasaki disease patients have coronary artery lesions and assessing the clinical treatment effect.

Assessment and Comparison of N-Terminal-Probrain Natriuretic Peptide (NT-proBNP) in Saliva and Serum of Healthy Subjects, Periodontitis Patients, and Periodontitis Patients With Myocardial Infarction.

Introduction Periodontitis is a multifactorial oral disease causing destruction of the periodontium. Systemic diseases can exacerbate periodontal inflammation through immune dysregulation. N-terminal-probrain natriuretic peptide (NT-proBNP) a prohormone, released by myocardial cells is a known biomarker for cardiovascular disease (CVD). Existing literature discloses a bidirectional relationship between periodontitis and CVD. NT-proBNP release can be regulated by mediators of the systemic inflammation. Cardiocyte NT-proBNP release might get stimulated through proinflammatory cytokines. NT-proBNP levels can also be influenced by systemic inflammation in the absence of cardiac dysfunction. Accordingly, we postulated that the inflammation of periodontium could aid in increased levels of NT-proBNP in serum and saliva in participants without cardiovascular disorders. Saliva is said to be the mirror of the body. Assessing NT-pro BNP in saliva allows for a non-invasive method. The present research evaluated the salivary and serum concentrations of NT-proBNP in a healthy group, patients suffering from periodontal disease and periodontal disease along with myocardial infarction (MI). Material and method A total of 90 patients, 30 in each group i.e., healthy group, periodontitis patients and patients suffering from periodontitis with myocardial infarction, were enrolled. The periodontitis patients were selected according to the Classification of Periodontal and Peri-implant Diseases and Conditions 2017. Patients clinically diagnosed with MI by the physician were selected following World Health Organization criteria for detection of MI. Case history was recorded and periodontal parameter analysis like plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL) were measured. Salivary and serum samples were collected from the participants after obtaining informed consent. The samples were subjected to human NT-proBNP sandwich type enzyme-linked immunosorbent assay (ELISA) for quantitative evaluation. The obtained data was analysed and compared using ANOVA, Tukey's post hoc test and Pearson's correlation. The p-value<0.05 was considered statistically significant. Result PI and GI were highest in subjects with periodontitis only (p<0.05). Patients suffering from periodontitis with MI exhibited significantly higher PPD and CAL values (p<0.05). Salivary and serum concentrations of NT-proBNP were significantly higher with p-value=0.000 in subjects suffering from periodontitis with MI. The salivary NT-proBNP levels were significantly higher than serum NT-proBNP levels in periodontitis and periodontitis with MI patients. The levels of NT-proBNP in periodontitis along with MI patients were 1.570 pg/mL in serum and 1.694 pg/mL in saliva. Conclusion Salivary NT-proBNP levels were highest in subjects affected from periodontitis along with MI. Elevated salivary NT-proBNP levels can be due to systemic inflammation and cardiovascular stress linking periodontitis to MI. The positive correlation between periodontal parameters and NT-proBNP levels validates the biomarker's role in reflecting the extent of periodontal destruction and its association with cardiovascular stress. Salivary NT-proBNP can be used as a non-invasive diagnostic marker for diagnosing periodontitis and MI. Future research could explore targeted therapies for the shared inflammatory pathways between periodontitis and MI.

Relationship between N-terminal pro-brain natriuretic peptide concentration and heart-type fatty acid-binding protein in postmortem urine

The clinical use of N-terminal pro-brain natriuretic peptide (NT-proBNP) and blood concentrations of heart-type fatty acid-binding protein (HFABP) is well-established in diagnosing heart conditions. However, their applicability in forensics is controversial due to postmortem changes. NT-proBNP and HFABP are excreted in the urine due to their small molecular weights and may be found in postmortem urine samples; however, their correlation has not been evaluated. In this study, we compared the concentrations of urinary NT-proBNP and HFABP in 386 forensic autopsy cases. The urinary NT-proBNP levels were significantly higher in acute myocardial infarction (AMI), congestive heart failure (CHF), sepsis, and hyperthermia cases, with the highest levels in CHF cases. Similarly, HFABP concentration was significantly higher in CHF, sepsis, and hyperthermia cases, with the highest level observed in hyperthermia cases. However, the difference in urinary HFABP levels between the AMI and control cases was not significant. Our analysis revealed a correlation between postmortem urine NT-proBNP and HFABP levels, and the NT-proBNP/HFABP ratio was high in patients with CHF and sepsis cases and low in those with hyperthermia. The difference between the ratios was possibly due to the combined release of ventricular myocardial cells in response to ventricular wall stress and myocardial injury for NT-proBNP, as well as myocardial and skeletal muscle injuries for HFABP. This study, for the first time, demonstrates the utility of postmortem measurements of urinary NT-proBNP and HFABP levels, offering valuable insights for improving the accuracy of postmortem diagnosis in forensic medicine.

Serum biomarkers in patients with psoriasis and coronary artery disease and their impact on hospitalization: data form a prospective, 4-year, single-center, uncontrolled study

Aim. To study serum biomarker profile in patients with coronary artery disease (CAD) and psoriasis and the impact on the incidence of hospitalization for cardiovascular reasons and psoriasis.Material and methods. The study included 90 patients divided into following 3 groups: with psoriasis (n=30), coronary artery disease (CAD) (n=30) and CAD+psoriasis (n=30) in whom serum biomarkers were determined at the beginning of the study (growth stimulation expressed gene 2, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-17 and tumor necrosis factor alpha) and hospitalization rates were monitored over 4 years.Results. There was a significant difference in the concentrations of all biomarkers between the groups (p&lt;0,05), with the maximum values being in the CAD+psoriasis group, except for NT-proBNP. In regression analysis, risk factors for cardiovascular hospitalizations were psoriasis (p=0,049) and increased NT-proBNP concentrations (p&lt;0,001).Conclusion. Comorbidity leads to an increase in the serum concentration of biomarkers, while the risk factors for cardiovascular hospitalization were psoriasis and serum NT-proBNP level.

Abstract 64: Biomarkers of Atrial Cardiopathy and Outcomes After Cryptogenic Stroke: The ARCADIA Trial

Background: Atrial cardiopathy is associated with incident ischemic stroke in the absence of clinical atrial fibrillation in prospective cohorts. Whether biomarkers of atrial cardiopathy predict recurrent stroke is less clear. Methods: In the ARCADIA trial, a multicenter randomized trial of apixaban versus aspirin in patients with cryptogenic stroke and evidence of atrial cardiopathy, we explored whether the biomarkers P-wave terminal force in ECG lead V 1 (PTFV1), N-terminal pro-Brain natriuretic peptide (NT-proBNP), or left atrial diameter index (LADI) predicted primary and secondary trial outcomes: (1) recurrent stroke of any type; (2) recurrent ischemic stroke or systemic embolism; and (3) recurrent stroke of any type or death. We analyzed the full cohort using Cox proportional hazard models , sequentially adjusting for treatment effect, demographic factors, and clinical risk factors. NT-proBNP concentrations were log-transformed. Results: With 1,015 of the target 1,100 participants enrolled (mean age 68 years, 54.3% female, 21.1% Black, and 8.1% Hispanic) and mean follow-up of 1.8 years, the trial was stopped for futility. Recurrent stroke occurred in 80 patients (annualized rate, 4.4%) and death in 54 patients. NT-proBNP significantly predicted recurrent stroke; recurrent ischemic stroke or systemic embolism; and recurrent stroke or death after adjusting for other risk factors, while PTFV1 and LADI did not (Table). NT-proBNP predicted recurrent stroke and death most strongly and with little change after adjusting for other risk factors. Treatment effect was not significant in any of the models. Conclusions: In this population of patients with cryptogenic stroke and evidence of atrial cardiopathy, NT-proBNP is a predictor of recurrent stroke and, with greater magnitude, of a composite of stroke or death. The role of NT-proBNP measurement in management after stroke deserves further study.

Improved heart function and cardiac remodelling following sacubitril/valsartan in acute coronary syndrome with HF.

This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6months after treatment when a clinical follow-up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non-ST-elevation myocardial infarction (NSTEMI) group, and ST-elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT-proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT-proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P<0.05), NT-proBNP, LVMI, and LVESVI decreased significantly in both groups after 6months (P<0.05), and LVEDVI decreased significantly in the S/V group (P=0.001). In the S/V group, ΔLVEF (t=-2.745, P=0.006), ΔNT-proBNP (P=0.009), ΔLVEDVI (t=4.203, P=0.001), and ΔLVESVI (t=3.907, P=0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT-proBNP (r=-0.244, P=0.004), ΔLVMI (r=-0.190, P=0.028), ΔLVEDVI (r=-0.173, P=0.045), and ΔLVESVI (r=-0.261, P=0.002). In Cox regression model analysis,ΔLVEF {hazard ratio [HR]=0.87 [95% confidence interval (CI) 0.80-0.95], P=0.003}, ΔLVEDVI [HR=1.04 (95% CI 1.01-1.06), P=0.013], and ΔLVESVI [HR=1.04 (95% CI 1.01-1.08), P=0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t=6.290, P=0.001), ΔLVEDVI (t=2.581, P=0.011), and ΔNT-proBNP (P=0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t=-3.365, P=0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t=-3.928, P=0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan-Meier curve (P=0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P=0.004). The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT-proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first-line heart failure treatment after PCI.

Clinical Significance of Apela in Acute Cardiorenal Insuffiency of Chronic Heart Failure

Introduction: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear. Methods: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hMC), and human renal tubular epithelial cells (HK-2) were observed. Results: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = −0.374) and 6-min walk distance (r = −0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the upregulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hMC, and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hMC but inhibited the upregulated expression of α-SMA and vimentin in HK-2 cells by AngII. Conclusion: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS.

Prognostic Role of Myocardial Flow Reserve in Heart Failure With Preserved Ejection Fraction.

Aim To study the role of myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with heart failure with preserved ejection fraction (HFpEF) in stratifying the risk of HFpEF progression during 12 months of follow-up.Material and methods The study included 58 patients with non-obstructive coronary artery disease and HFpEF. Concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using an enzyme-linked immunosorbent assay. MFR and MBF were determined by dynamic single-photon emission computed tomography of the myocardium.Results At 12 months, the patients were divided into two groups: group 1 (n=11) included patients with an unfavorable course of HFpEF, group 2 (n=47) included patients with a favorable course. A multivariate analysis showed that NT-proBNP concentrations (odds ratio (OR), 3.23; 95% confidence interval (CI), 1.76-6.78; p=0.008) and MFR (OR, 8.09; 95% CI, 5.12-19.98; p&lt;0.001) were independent predictors of adverse outcomes. According to ROC analysis, values of MFR ≤1.62 (area under the curve (AUC)=0.827; p&lt;0.001) and NT-proBNP ≥760.5 pg/ml (AUC=0.708; p=0.040) can be considered as markers for HFpEF progression. Furthermore, the combined measurement of NT-proBNP concentration and MFR had a higher prognostic significance (AUC, 0.954; p&lt;0.001).Conclusion Values of NT-proBNP and MFR can be used as noninvasive markers for an unfavorable course of HFpEF, and their combined measurement increases the prognostic significance.

The Clinical Evolution of Diffuse Myocardial Fibrosis in Patients With Arterial Hypertension and Heart Failure With Mildly Reduced Ejection Fraction Treated by Olmesartan or Sacubitril / Valsartan.

Aim A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan in patients with arterial hypertension (AH) and dyslipidemia in the dynamics of the following indicators of chronic heart failure (CHF): N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), LV global longitudinal strain (LV GLS) in diffuse myocardial fibrosis (MF) previously diagnosed by magnetic resonance imaging (MRI).Material and methods Olmesartan medoxomil (n=56) and sacubitril/valsartan (n=63) were used for 12 months in patients with hypertension, dyslipidemia and NYHA functional class II-III CHF with mid-range LVEF (CHFmrEF). MF was diagnosed by the following MRI criteria: late gadolinium enhancement and an increased proportion of extracellular matrix (33% or more). The frequency of persisting late gadolinium enhancement and the increased proportion of extracellular matrix (33% or more) was evaluated at 12 months; changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), NT-proBNP, and LV GLS were evaluated after 3, 6, and 12 months of follow-up.Results Baseline parameters did not differ between groups. The late gadolinium enhancement and increased proportion of extracellular matrix were present at baseline in all patients of both groups (100%; p=1.0). Already at 3 months, statistically significant decreases in SBP and DBP were observed in both groups. In addition, the LV GLS monitoring showed LV GLS significantly increased in both groups after 3 months and continued changing after 6 and 12 months. The NT-proBNP concentration significantly decreased in both groups already after 3 months and continued to decrease after 6 and 12 months. At 6 and 12 months, sacubitril/valsartan was superior to olmesartan in reducing SBP and NT-proBNP and in restoring LV GLS. At 12 months, the incidence of persisting, abnormal late gadolinium enhancement and increased proportion of extracellular matrix was significantly less in the ARNI group.Conclusion Olmesartan was demonstrated effective in the multi-modality therapy of CHFmrEF and MF in patients with AH and dyslipidemia. ARNI was superior to olmesartan in this regard, but further research of this issue is required.

The Interplay between Adipose Tissue Properties and Levels of NT-proBNP in People with HIV.

We aimed to assess the association between low N-terminal pro-brain natriuretic peptide (NT-proBNP) and body mass index (BMI), adipose tissue distribution, adiponectin, and HIV-specific risk factors among people with HIV (PWH). We included 811 PWH with measurement of height, weight and waist circumference, blood samples analyzed for NT-proBNP, and visceral-(VAT) and subcutaneous (SAT) adipose tissue areas measured from CT-scans. Low concentrations of NT-proBNP were defined as concentrations below the limit of quantification (5.9 pmol/L). Associations were explored with multivariable logistic regression analyses adjusted for relevant confounders. We identified 471 (58%) individuals with low concentrations of NT-proBNP. Increasing BMI was associated with higher odds of low NT-proBNP (adjusted OR (aOR) 1.06 (95% CI: 1.01-1.11) per 1 kg/m2). Central obesity and large areas of VAT were associated with higher odds of low NT-proBNP (aOR 1.66 (1.16-2.36) and aOR 1.69 (1.09-2.62), respectively). Higher adiponectin was associated with lower odds of low NT-proBNP (aOR 0.86 (0.79-0.95) per 10% increase). No associations were found between low NT-proBNP and HIV-specific risk factors. In PWH, low NT-proBNP is associated with an adverse adipose tissue profile with high BMI, central obesity, accumulation of VAT, and low adiponectin.

Variations in NT-proBNP Levels in Pregnant Patients with and without SARS-CoV-2 Infection: Consequences for the Newborns.

NT-proBNP (N-terminal pro-brain natriuretic peptide) has a high negative predictive value for ruling out heart failure, a disorder linked with volume overload of the ventricles, and is used for diagnosis, prognosis, and risk stratification. Pregnancy causes in healthy women changes in physical and hemodynamic parameters and appears to be a risk factor for severe COVID-19 illness. The purpose of this study is to highlight the significance of monitoring NT-proBNP levels during pregnancy, particularly in patients who were infected with COVID-19 during pregnancy or were infected with the virus while giving birth. The findings of this comparative research indicate the importance of NT-proBNP in terms of foetal prognosis and birthweight. We collected blood samples to measure NT-proBNP concentrations from a cohort of 186 pregnant patients divided into two groups based on the presence of SARS-CoV-2 viral infection. Elevated NT-proBNP had an unfavourable implication on the newborn birth weight and Apgar score and expressed its influence on lower values. We consider that NT-proBNP testing in pregnant patients, especially those with COVID-19 infection, can be relevant and be used as a predictive marker to be taken into consideration when it comes to management, outcome, and treatment regarding pregnant patients and their newborns.

Assessment of N-terminal pro-brain natriuretic peptide in patients with arrhythmia due to undifferentiated connective tissue disease

Aim. To study the relationship between the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and myocardial abnormalities in patients with cardiac arrhythmias due to undifferentiated connective tissue disease (UCTD).Material and methods. This cross-sectional comparative study included young and middle-aged patients with arrhythmias due to UCTD: group 1 (18-44 years old, n=127), group 3 (45-59 years old, n=10). The control groups (n=30, group 2; n=8, group 4) included volunteers with single phenotypic signs of UCTD, comparable in age and sex. A standard clinical examination, 72-hour electrocardiographic monitoring, Speckletracking echocardiography, and NT-proBNP level assessment were performed.Results. In patients of groups 1 and 3, a significant increase in the concentration of NT-proBNP was noted compared to the control groups. At the same time, the average NT-proBNP level in the study groups did not exceed the reference values. Significant correlations were revealed between NT-proBNP and heart rate (r1=0,462, p=0,010; r3=0,397, p=0,034), UCTD diagnostic cut-off level (r1=0,496, p=0,001; r3=0,401, p=0,043), the presence of mitral valve prolapse (r1=0,469, p=0,002) and mitral regurgitation (r1=0,53, p=0,008), premature ventricular contractions (PVCs) of class III (r1=0,582, p=0,045), IVa (r1= 0,39, p=0,042) and V (r1=0,397, p=0,037); cardiac index (r1=-0,329, p=0,037) and ejection fraction (r1=-0,407, p=0,044). However, no significant correlation was found between the left ventricular global longitudinal strain and NT-proBNP level.Conclusion. The study demonstrated the association of NT-proBNP level with UCTD diagnostic cut-off level, mitral valve prolapse, mitral regurgitation, and PVCs, which makes possible the use of this biomarker as an additional diagnostic criterion for myocardial changes in against the background of UCTD.

The association between plasma N-terminal pro-brain natriuretic peptide concentration and metabolic disturbances in women with depressive symptoms

BackgroundThe relationship between brain natriuretic peptides and depression was studied in patients with cardiovascular diseases (CVD), but the data in people without CVD are limited. Metabolic disturbances can be associated with natriuretic peptides’ levels. The study aimed to assess serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in women with depressive symptoms and its relationship with metabolic disturbances. MethodsThe analysis included 347 women (20–60 years old) from Bialystok PLUS cohort study: 98 with depressive symptoms and 249 controls. Clinical examination, oral glucose tolerance test (OGTT) and assessment of lipid, sex hormone binding globulin (SHBG) and NT-proBNP concentrations in the blood were performed. The participants completed Beck Depression Inventory questionnaire. ResultsMetabolic syndrome was more frequent in the group of women with depressive symptoms compared to women without depressive symptoms. Women with depressive symptoms had lower NT-proBNP level than the control group - 45.88 (27.80–67.04) vs 56.49 (32.42–94.25) pg/mL, p = 0.027. Multiple linear regression analysis of all women showed that NT-proBNP level was reversely associated with the presence of depressive symptoms, waist circumference and heart rate and positively connected with age. In the group of women with depressive symptoms, we observed negative correlations between NT-proBNP level and insulin concentration at 60 min of OGTT, diastolic blood pressure and a positive correlation with SHBG. ConclusionsNT-proBNP level is decreased in women with depressive symptoms, which might be connected with metabolic disturbances in this group.

Simultaneous detection method for two cardiac disease protein biomarkers on a single chip modified with mixed aptamers using surface plasmon resonance

A simultaneous detection method for two cardiac disease protein biomarkers present in serum samples on a single planar gold chip using surface plasmon resonance (SPR) is described. The detection of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tumor necrosis factor α (TNF-α), which are known as acute myocardial infarction (AMI) biomarkers, with predetermined clinically relevant concentrations was performed using mixed aptamers specific to each protein tethered on a single gold surface. After the binding of NT-proBNP and/or TNF-α to the mixed aptamers, an antibody specific to each target protein was injected to form a surface sandwich complex to improve selectivity. In order to adjust the dynamic ranges in the known clinically relevant concentration significantly different for NT-proBNP (0.13–0.24 nM) and TNF-α (0.5–3 pM), the surface density ratios of the corresponding pair of aptamer and antibody were first systematically determined, which were the 1:1 mixed aptamer chip with 40 nM anti-NT-proBNP and 100 nM anti-TNF-α. This allowed to establish the distinct dynamic ranges of 0.05–0.5 nM for NT-proBNP and 0.1–5 pM for TNF-α in a buffer, along with detection and quantification limits of 0.03 and 0.19 nM for NT-proBNP and 0.06 and 0.21 pM for TNF-α, respectively. The changes in refractive unit (RU) values observed when exposing both proteins at different concentrations alongside the corresponding fixed concentration of antibodies onto the 1:1 mixed aptamer chip were then correlated to the sum of RU values measured when using the injection of individual protein for evaluating each protein concentration. With a complete characterization of the simultaneous quantification of two protein concentrations in the buffer, the mixed aptamer chip was finally employed for direct measurements of NT-proBNP and TNF-α concentrations in undiluted serum samples from healthy controls and AMI patients. The results of simultaneous SPR measurements for the two proteins in the serum samples were further compared to the individual protein concentration results using an enzyme-linked immunosorbent assay.

Clinical characteristics and prognosis of patients with heart failure and high concentrations of interleukin-17D

AimsHeart failure (HF) is associated with cytokine activation and inflammation. Experimental evidence suggests that plasma interleukin-17 (IL-17) is associated with myocardial fibrosis and cardiac dysfunction in HF. IL-17D, a subtype of IL-17 originates from particular tissues such as the heart. However, there is very limited data on the IL-17 cytokine family in patients with HF. Therefore, we investigated the association between circulating IL-17D levels, clinical characteristics and outcome in a large cohort of patients with heart failure. Methods and resultsPlasma IL-17D was measured in 2032 patients with HF from 11 European countries using a proximity extension assay. The primary outcome was a composite of HF hospitalization or all-cause mortality. Patients with higher plasma IL-17D concentrations were more likely to have atrial fibrillation (AF), renal dysfunction and heart failure with preserved ejection fraction (HFpEF) and had higher plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations (all p < 0.001). IL-17D was not associated with interleukin-6 (IL-6) or C-reactive protein (CRP) concentrations. After adjustment for confounders in a multivariable Cox regression analysis, patients in the highest quartile of plasma IL-17D had a significantly increased risk of the composite outcome of HF hospitalization or all-cause mortality compared to patients in the lowest quartile [Hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05–1.57]. ConclusionIn patients with HF, elevated plasma IL-17D concentrations are associated with higher plasma NT-proBNP concentrations and a higher prevalence of AF and renal dysfunction. High IL-17D concentrations are independently associated with worse outcome.

Importance of blood biomarker determination in the selection of patients with heart failure for cardioverterdefibrillator implantation

Aim. To conduct a comparative analysis of blood biomarker concentrations, to study their prognostic role in the occurrence of sustained ventricular tachyarrhythmia (VT) or VT episodes requiring electrotherapy in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤35% without prior syncope or sustained ventricular arrhythmias.Material and methods. This single-center prospective clinical study included 319 patients (men, 83%) aged 57 (51-63) years with LVEF of 29 (24-33)% receiving optimal therapy for HF, hospitalized for cardioverterdefibrillator implantation for the purpose of primary prevention of sudden cardiac death. Before the procedure, the concentration of blood biomarkers (blood electrolytes, C-reactive protein, creatinine, Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), galectin-3) was determined. Based on blood creatinine concentration, glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Patients underwent a two-year prospective follow-up to record the end point of newly occurring clinically significant VT episodes detected by an implantable cardioverter-defibrillator.Results. The studied arrhythmic endpoint occurred in 84 (26,3%) patients. The multivariate analysis revealed three blood biomarkers, the concentration of which was associated with the first manifestation of VT. With sST-2 &gt;35 ng/ml, this risk increased by ~3 times (odds ratio (OR)=2,86; 95% confidence interval (CI): 1,23-6,64 (p=0,013)). Galectin-3 level &gt;12 ng/ml had a comparable prognostic value (OR=2,64; 95% CI: 1,06-6,53 (p=0,032)). In case of an increase in NT-proBNP &gt;2000 pg/ml, the risk of the same outcome was 2,2 times lower (OR=0,46; 95% CI: 0,22-0,95 (p=0,034)).Conclusion. Pre-implantation laboratory screening of NT-proBNP, sST-2 and galectin-3 concentrations can help in personalized assessment of arrhythmic risk in patients with HF and LVEF ≤35% referred for interventional primary prevention of sudden cardiac death.

Oligosaccharides and diet-related dilated cardiomyopathy in beagles.

In 2018 the US Food and Drug Administration reported a potential link between grain-free, legume-containing dog foods and the development of canine dilated cardiomyopathy in atypical breeds. One hypothesis was that high oligosaccharide content in legumes reduced bioavailability of taurine, an amino acid with some previous links to canine dilated cardiomyopathy. To address this hypothesis, in the present study, 8 Beagle dogs consumed four diets: a husbandry commercial dental diet, and three test diets formulated with either 30% rice (control), 30% pea (grain-free) or 30% rice with the addition of 1% raffinose (the predominant oligosaccharide found in peas). The study was conducted in a randomized, crossover design with 5 week feeding periods. Measurement of basic health parameters (weight, body condition score, complete blood cell count, chemistry panel), plasma amino acids, cardiac biomarkers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac-specific troponin I), fecal bile acids and echocardiographic exams were completed pre-study after feeding the husbandry diet as well as after each test feeding period. Echocardiography showed 9-11% reduction in ejection fraction and 17- 20% greater left ventricular end systolic volume with the husbandry diet compared to both grain-containing test diets. Concentrations of plasma NT-proBNP were 1.3-2 times greater after the husbandry diet compared to the grain-based diet, with the oligosaccharide and pea-based diets showing intermediate levels. Plasma taurine levels were unchanged across diets, while plasma methionine levels were highest and cysteine/cystine levels were lowest after dogs ate the husbandry diet. Results indicate that raffinose in the diet is sufficient, but not required to see an increase NT-proBNP, but did not induce any changes in cardiac function after 5 weeks of feeding. Whether this could progress to reduction in cardiac function with longer term feeding is uncertain. A reduced cardiac function along with the greatest increase in NT-proBNP was observed after feeding the husbandry diet that contained the highest amount of insoluble fiber but did not contain legumes or oligosaccharide. Further research into the impact of insoluble fiber in the dental diet is needed to support these novel observations.