Changes In B-type Natriuretic Peptide Research Articles

Abstract 4137311: Inhibition of IL-33 by tozorakimab in patients with diabetic kidney disease: Cardiovascular insights from FRONTIER-1

Introduction: Interleukin-33 (IL-33) is a potent mediator of injury-induced local inflammation. Soluble ST2 (sST2), a decoy receptor of IL-33, is a prognostic serum biomarker for heart failure (HF). Here, we evaluated the impact of tozorakimab, an IL-33-neutralizing monoclonal antibody, on sST2-related secondary cardiac endpoints. Methods: FRONTIER-1 was a 24-week phase 2B study (NCT04170543) in patients with diabetic kidney disease (DKD). Key cardiac exclusion criteria were: 1) NYHA Class 3/4; 2) Left ventricular ejection fraction (LVEF) < 40%; 3) B-type natriuretic peptide (BNP) > 200 pg/mL. Local echocardiography (LVEF) was performed at Screening and Week 24. For exploratory analysis, echocardiography recordings were evaluated by a core laboratory. Throughout the study, BNP and sST2 were assessed and adverse events (AE) recorded. Safety and tolerability were evaluated for all dosed participants (Safety Analysis Population, SAP). Results: 573 participants were included in the SAP (139 = placebo / 434 = tozorakimab). Baseline characteristics were balanced across treatment groups. Tozorakimab was generally well tolerated and the incidences of AE, serious AE (SAEs), discontinuations, and death were similar to placebo. In the placebo group, cardiac disorder AE were reported in 6.5%, and SAE in 2.2%. Decline in LVEF of > 10% was seen in 5 participants (4.3%). None developed BNP > 200 pg/mL or clinical signs of HF. 1 participant (0.7%) presented with clinical symptoms of HF (SAE) without significant changes in LVEF or BNP. On tozorakimab, cardiac disorder AE/SAE were less frequent (3.7%/1.8%). Decline in LVEF of > 10% was observed in 31 participants (8.3%), with 3 showing BNP elevation to 200–308 pg/mL. Two of these participants (0.5%) developed clinical signs of HF with LVEF 55%/30% and BNP < 200 pg/mL. No further AE related to HF were reported for tozorakimab. Central analysis of LVEF revealed a substantial variability of site-based measurements indicating LVEF reductions > 10 % in 2 (3.7%) participants on placebo and 6 (2.9%) on tozorakimab. Furthermore, central exploratory analysis demonstrated a slight increase in LVEF from baseline (1.62%, 95% CI: 0.22, 3.03) and a reduction in average E/e' (-0.47, 95% CI: -0.93, -0.01) for tozorakimab, but not placebo. Trends in BNP and sST2 over time were comparable. Conclusion: This study suggests a favorable cardiac safety profile for tozorakimab in patients with DKD. IL-33 inhibition did not elevate serum sST2 significantly.

Association Between Serial B-Type Natriuretic Peptide Levels, Vasoactive Drug Weaning, and Adverse Cardiovascular Outcomes in Pediatric Heart Failure.

Children hospitalized with acute decompensated heart failure (ADHF) frequently require intravenous vasoactive (IVV) support drugs and are at risk for adverse cardiovascular (ACV) outcomes. We wished to assess whether serial changes in B-type natriuretic peptide (BNP) levels are associated with successful weaning off IVV support and/or prespecified ACV outcomes in children hospitalized with ADHF. Children hospitalized with ADHF from 2005 to 2021 at our institution were assessed for serial changes in BNP, weaning off of IVV support, and ACV outcomes. Changes in BNP level were evaluated using linear mixed-effects modeling. Bonferroni correction was used to adjust for multiple hypothesis testing. In 131 hospitalizations of children with ADHF, the median age was 4.8 years, with 74% receiving IVV support. ACV outcomes occurred in 62 children. IVV support was associated with lower admission left ventricular ejection fraction (26.7% versus 32%, P=0.002), more severe left ventricular dilation (left ventricular internal diastolic dimension Z score 5.9 versus 3.1, P=0.021) moderate or more mitral regurgitation (41.3% versus 20.6%, P=0.038), and qualitative right ventricular systolic dysfunction (in 45.4% versus 11.8%, P<0.001). Decline in BNP levels was more rapid in patients who were successfully weaned from IVV support (-0.20 versus -0.03 2log pg/mL per day, P<0.001) and in the non-ACV group (-0.17 versus -0.03 2log pg/mL per day, P<0.001). Right ventricular systolic dysfunction was an independent risk factor for ACV (odds ratio, 2.49; P=0.045). The declining rate of serial BNP levels was associated with weaning from IVV support and no ACV outcomes in children hospitalized with ADHF. Right ventricular systolic dysfunction was associated with ACV outcomes.

B-type natriuretic peptide levels predict long-term mortality in a large cohort of adults with congenital heart disease.

Many adult patients with congenital heart disease (ACHD) are still afflicted by premature death. Previous reports suggested natriuretic peptides may identify ACHD patients with adverse outcome. The study investigated prognostic power of B-type natriuretic peptide (BNP) across the spectrum of ACHD in a large contemporary cohort. The cohort included 3392 consecutive ACHD patients under long-term follow-up at a tertiary ACHD centre between 2006 and 2019. The primary study endpoint was all-cause mortality. A total of 11 974 BNP measurements were analysed. The median BNP at baseline was 47 (24-107) ng/L. During a median follow-up of 8.6 years (29 115 patient-years), 615 (18.1%) patients died. On univariable and multivariable analysis, baseline BNP [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.15-1.18 and HR 1.13, 95% CI 1.08-1.18, respectively] and temporal changes in BNP levels (HR 1.22, 95% CI 1.19-1.26 and HR 1.19, 95% CI 1.12-1.26, respectively) were predictive of mortality (P < .001 for both) independently of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. Patients within the highest quartile of baseline BNP (>107 ng/L) and those within the highest quartile of temporal BNP change (>35 ng/L) had significantly increased risk of death (HR 5.8, 95% CI 4.91-6.79, P < .001, and HR 3.6, 95% CI 2.93-4.40, P < .001, respectively). Baseline BNP and temporal BNP changes are both significantly associated with all-cause mortality in ACHD independent of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. B-type natriuretic peptide levels represent an easy to obtain and inexpensive marker conveying prognostic information and should be used for the routine surveillance of patients with ACHD.

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R=-0.30, P<0.001) and fewer daily steps (R=-0.19, P=0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6months were positively related (R=0.25, P=0.004). This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

Propensity-score matched comparison of renal and neurohormonal effects of catheter ablation for frequent premature ventricular contractions in patients with and without systolic dysfunction.

Catheter ablation (CA) for premature ventricular contractions (PVCs) restores cardiac and renal functions in patients with reduced left ventricular ejection fraction (LVEF); however, its effects on preserved EF remain unelucidated. The study cohort comprised 246 patients with a PVC burden of >10% on Holter electrocardiography. Using propensity matching, we compared the changes in B-type natriuretic peptide (BNP) levels and estimated glomerular filtration rate (eGFR) in patients who underwent CA or did not. Postoperative BNP levels were decreased significantly in the CA group, regardless of the degree of LVEF, whereas there was no change in those of the non-CA group. Among patients who underwent CA, BNP levels decreased from 44.1 to 33.0 pg/mL in those with LVEF ≥50% (p = .002) and from 141.0 to 87.9 pg/mL in those with LVEF <50% (p < .001). Regarding eGFR, postoperative eGFR was significantly improved in the CA group of patients with LVEF ≥50% (from 71.4 to 74.7 mL/min/1.73 m2, p = .006), whereas it decreased in the non-CA group. A similar trend was observed in the group with a reduced LVEF. Adjusted for propensity score matching, there was a significant decrease in the BNP level and recovery of eGFR after CA in patients with LVEF >50%. This study showed that CA for frequent PVCs decreases BNP levels and increases eGFR even in patients with preserved LVEF.

BS O07 Short-Term and Long-Term Changes in Natriuretic Peptide Levels After Bariatric Surgery: A Meta-Analysis

Abstract Background Bariatric surgery (BS) has demonstrated cardiovascular benefits in patients and was previously proven to be associated with an increased natriuretic peptide level without cardiac dysfunction. However, new studies have emerged, which require us to re-examine the relationship and extent of the correlation between BS, weight loss, and cardiac natriuretic peptide levels. Methods A PRISMA-compliant systematic search was conducted across Medline, Cochrane, and Embase, until 15th February 2023. Primary outcomes include short- and long-term changes in B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) post-BS. Secondary outcomes included changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), atrial natriuretic peptide (ANP), N-Terminal atrial natriuretic peptide (NT-ANP), ejection fraction (EF) and left ventricular mass (LVM). Outcomes were pooled using the DerSimonian and Laird random effects model. Results Twenty-two studies with 1219 patients (33.2% Male, 45.5% gastric bypass surgery). Mean difference of short- and long-term NT-proBNP levels after BS were 52.88 pg/mL (95% CI, 21.30-84.46) and 50.42 pg/mL (95% CI, 28.18-72.67) respectively with a similar rise observed in BNP levels. Short-term NT-ANP levels significantly increased, but not in long-term ANP and short-term NT-ANP levels. There were no significant post-BS changes in EF but SBP, DBP and LVM significantly reduced. Subgroup analysis in NT-proBNP levels demonstrated a significant rise among patients with &amp;gt;30% BMI loss and a significant reduction in patients with &amp;lt;30% BMI loss. Conclusions BS is associated with increased natriuretic peptide levels in the absence of deteriorating cardiac function. Further studies should investigate its correlation with clinical symptoms, cardiac structural changes and the longitudinal risk of heart failure, enabling informed decision-making and tailored management strategies to optimize patient care and improve postoperative cardiac outcomes in the context of BS.

Effectiveness and safety of transcatheter aortic valve replacement in elderly people with severe aortic stenosis with different types of heart failure

BackgroundImpaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure.MethodsThis was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR.ResultsA total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p < 0.05), and with a higher BNP (p < 0.05). The left ventricular end-diastolic dimension (LVEDD) in HFrEF group decreased significantly after TAVR. HFmrEF and HFrEF patients showed significant improvements in LVEF after TAVR. The pulmonary artery systolic pressure (PASP), aortic valve peak gradient (AVPG) and aortic valve peak gradient (Vmax) decreased significantly 1 month after TAVR in all three groups compared to the baseline (all p < 0.05). BNP significantly reduced in HFrEF group compared to HFpEF patients after TAVR (p < 0.05). The majority of patients experienced an improvement at least one NYHA class in all three groups 6 months post-TAVR. There is no significant increase in the risk of adverse events in the HFrEF group.ConclusionsPatients who underwent TAVR achieved significant improvements in BNP, NYHA class, LVEDD, LVEF, and PASP across the three HF classes, with a more rapid and pronounced improvement in the HFrEF and HFmrEF groups. Complication rates were low in the different HF groups. There is no significant increase in the risk of periprocedural complications in the HFrEF and HFmrEF groups.

LBODP028 Identifying Biomarkers For Predicting Response To Mineralocorticoid Receptor Antagonist Treatment In Heart Failure

Abstract Despite significant improvements to patient care, heart failure (HF) remains a major public health burden. Mineralocorticoid receptor antagonists (MRAs) reduce hospitalisation and improve survival in patients with HF with reduced ejection fraction (HFrEF) but the widespread use of MRAs is limited by adverse effects including hyperkalaemia. The use of biomarkers to guide therapy may enable earlier treatment or minimise side effects from unnecessary therapies. We have previously described mineralocorticoid receptor responsive genes in monocytes/macrophages and hypothesised that response to MRAs can be detected in this cell population. Therefore, we aimed to identify biomarkers for predicting response to MRAs to facilitate personalised treatment of HF. Microarray-based transcriptome profiling was performed on monocytes obtained from six patients with HFrEF, before and after three months of MRA treatment. Three patients demonstrated improvement in left ventricular ejection fraction (LVEF) after 12 months of MRA treatment (Group 1), whereas the other three patients exhibited minimal functional response to MRAs (Group 2). To visualise sample similarity, multidimensional scaling (MDS) was employed which revealed distinct separation of males from females. To understand the changes in monocyte gene expression following MRA treatment, differential expression analysis was performed. Paired analysis of Group 1 samples (before vs after MRA treatment) identified 319 unique differentially expressed genes (DEGs) with an estimated fold-change ≥ 2 and q-value &amp;lt; 0. 05; 1 upregulated, 318 downregulated, and paired analysis of Group 2 identified 1 unique DEG. RT-qPCR was used validate top DEGs implicated in cardiovascular pathophysiology which confirmed downregulation of 12 of the top DEGs in Group 1. Additionally, cluster of differentiation (CD) encoding genes CD14, CD163, and CD68 were upregulated in Group 1 but downregulated in Group 2. Additional differential expression analyses were also performed by stratifying patients according to additional metrics of functional response including change in B-type natriuretic peptide (BNP). However, these analyses did not identify statistically significant DEGs. Our results indicate MRA treatment can significantly alter the human monocyte transcriptomic profile. Further research is needed to establish the utility of these DEGs as biomarkers for early prediction of MRA treatment-response in patients with HF, and to define sex-specific differences. Presentation: No date and time listed

The effect of subclinical thyroid dysfunction on B- type natriuretic peptide level

Thyroid hormones (THs) have a significant effect on the cardiovascular system. THs increase myocardium stretch, leading to the release of B-type Natriuretic Peptide (BNP), which is considered a diagnostic biomarker of heart failure (HF). Thyroid dysfunctions (subclinical hypothyroidism; SCH and subclinical hyperthyroidism; SCHyper) stimulate several changes in the heart by causing either diastolic or systolic left ventricular dysfunctions leading to HF. This study aims to measure the changes of B- type NP levels in cases of subclinical hypo and hyperthyroidism. The present study aims to measure the changes in B-type Natriuretic Peptide (BNP) levels in subclinical hypo and hyperthyroidism (SCH and SCHyper). A theoretical study was also conducted using a docking program to find the effectiveness of some drugs in inhibiting or promoting B-type Natriuretic Peptide (BNP). A case study was conducted in a private clinic, Mosul- Iraq, from (April 1st – Sep 1) 2021, with 25 healthy participants with normal functioning thyroids as a control group (EU). A newly diagnosed 25 SCH and 17 SCHyper patients participated in this study, considering that none of them have thyroid dysfunctions taking medicine, hypertension, heart diseases, renal failure, and pregnant women. They all were checked for Thyroid Function Tests (TFTs), Free Triiodothyronine (FT3), Free Thyroxin (FT4) and Thyroid Stimulating Hormone (TSH). The plasma level of BNP was measured in all participants of the three groups. The results showed that the plasma level of BNP was higher in SCHyper patients (10.97 pg/ml) as compared to that of SCH patients (8.09 pg/ml) and EU subjects (8.27 pg/ml). Hereby, we could state that subclinical hyperthyroidism, SCHyper, triggers BNP release. Therefore, it should be kept in mind that any high BNP levels due to SCHyper should be considered a reliable diagnostic biomarker of heart failure (HF). Keywords. Thyroid hormone(TH), Subclinical hypothyroidism(SCH), Subclinical hyperthyroidism(SCHyper), Chronic heart disease(CHD), Heart failure(HF), B-type natriuretic peptide(BNP), Docking Study.

Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure

BackgroundThe endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization. ObjectivesThe purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk. MethodsParticipants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations. ResultsAmong 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78). ConclusionsIn patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532)

Positive relationships between annual changes in salt intake and plasma B-type natriuretic peptide levels in the general population without hypertension and heart diseases.

Excessive salt intake causes hypertension and heart diseases. B-type natriuretic peptide (BNP) is a surrogate marker of heart disease, and a slightly elevated BNP level is associated with a poor prognosis. Our previous cross-sectional study demonstrated that plasma BNP has a significant positive association with daily salt intake in the general population. However, the relationship between changes in salt intake and changes in plasma BNP remains unknown. We recruited 3051 participants without hypertension or electrocardiogram abnormalities who underwent annual health check-ups for two consecutive years. Clinical parameters, including plasma BNP, were obtained, and daily salt intake was evaluated using urinary samples. Annual changes in these parameters were calculated. The median plasma BNP level was 12.9 pg/mL, and the daily salt intake was 8.73 ± 1.89 g. The annual changes in plasma BNP and daily salt intake were 4.79 ± 36.38% and 2.01 ± 21.80%, respectively. Participants in the highest quartile of annual changes in daily salt intake showed the largest annual changes in plasma BNP. Annual changes in plasma BNP indicated a significant positive association with daily salt intake. Moreover, multiple linear regression analyses revealed that annual changes in plasma BNP showed a significant positive association with daily salt intake after adjustments. Our study showed a significant positive relationship between annual changes in plasma BNP and annual changes in daily salt intake. The suppression of plasma BNP is therefore induced by salt intake restriction. The monitoring of plasma BNP while reducing salt intake may therefore prevent heart diseases and lead to improved prognoses in the general population without heart diseases.

Heterogeneity Of Early B-type Natriuretic Peptide Change In HFrEF Patients Treated With Sacubitril/Valsartan

<h3>Introduction</h3> Through inhibition of neprilysin, sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor (ARNI), may cause initial increase in B-type natriuretic peptide (BNP) concentrations. The frequency, variability, and predictors of BNP rise during treatment of heart failure with reduced ejection fraction (HFrEF) from Sac/Val are not well-described. <h3>Hypothesis</h3> Changes in BNP after initiation of Sac/Val in HFrEF are variable and correlate with changes in NT-proBNP and ucGMP. <h3>Methods</h3> We classified BNP changes from baseline (pre Sac/Val) to Weeks 4 and12 among 367 patients treated with Sac/Val (regardless of dose) in an individual patient data analysis pooled from the EVALUATE-HF (n=221) and PROVE-HF (n=146) studies. Clinical predictors of BNP changes to Week 12 were analyzed in linear regression models and correlations with changes in NT-proBNP and ucGMP were examined using Spearman's rank correlation coefficient (rho). <h3>Results</h3> Across the two trials, median [IQR] concentration of BNP at Baseline, Week 4 and Week 12 was 145 [55, 329], 136 [50, 338] and 135 [51, 299] ng/L, respectively. There was no significant change from baseline to Week 4 (0% [-30%, +41%], p=0.36) or Week 12 (+1% [-36%, +50%], p=0.97). In adjusted analyses, predictors of BNP rise were similar to those of NT-proBNP rise and included atrial fibrillation, worse renal function, lower BMI, and lower concentrations of BNP/NT-proBNP at baseline (<b>Figure</b>). Change in BNP was strongly and linearly associated with change in NT-proBNP (rho=0.81, p<0.001), and the median [IQR] NT-proBNP change/BNP change was 66% [51%, 86%] (<b>Figure</b>). In contrast, change in BNP was only weakly associated with change in ucGMP (rho=0.19, p<0.001), and increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34%, +115%]), unchanged (+34% [-15%, +205%]), or increased (+57% [-12%, +14%]). <h3>Conclusions</h3> In this pooled analysis, following initiation of Sac/Val in HFrEF there was no significant overall increase in BNP concentrations. Early changes in BNP correlated closely with change in NT-proBNP but weakly with changes in ucGMP. Patients treated with Sac/Val demonstrate increase in ucGMP regardless of the BNP trajectory. These data argue against use of BNP rise as a biomarker of Sac/Val efficacy in HFrEF

Decongestion, kidney injury and prognosis in patients with acute heart failure

BackgroundIn patients with acute heart failure (AHF), the development of worsening renal function with appropriate decongestion is thought to be a benign functional change and not associated with poor prognosis. We investigated whether the benefit of decongestion outweighs the risk of concurrent kidney tubular damage and leads to better outcomes. MethodsWe retrospectively analyzed data from the AKINESIS study, which enrolled AHF patients requiring intravenous diuretic therapy. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and B-type natriuretic peptide (BNP) were serially measured during the hospitalization. Decongestion was defined as ≥30% BNP decrease at discharge compared to admission. Univariable and multivariable Cox models were assessed for one-year mortality. ResultsAmong 736 patients, 53% had ≥30% BNP decrease at discharge. Levels of uNGAL and BNP at each collection time point had positive but weak correlations (r ≤ 0.133). Patients without decongestion and with higher discharge uNGAL values had worse one-year mortality, while those with decongestion had better outcomes regardless of uNGAL values (p for interaction 0.018). This interaction was also significant when the change in BNP was analyzed as a continuous variable (p < 0.001). Although higher peak and discharge uNGAL were associated with mortality in univariable analysis, only ≥30% BNP decrease was a significant predictor after multivariable adjustment. ConclusionsAmong AHF patients treated with diuretic therapy, decongestion was generally not associated with kidney tubular damage assessed by uNGAL. Kidney tubular damage with adequate decongestion does not impact outcomes; however, kidney injury without adequate decongestion is associated with a worse prognosis.

Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration.

Cheyne-Stokes respiration (CSR), a kind of central sleep apnea, is referred to as a poor prognostic factor in heart failure patients with reduced ejection fraction (HFrEF). Matrix metalloproteinase (MMP) and B-type natriuretic peptide (BNP) play important roles in HFrEF patients and are markers of poor prognosis. However, there is no literature mentioning the changes in MMP and BNP in HFrEF patients with CSR. From June 2018 to June 2019, 41 adult patients with stable heart failure and left ventricular ejection fraction < 50% were enrolled from the cardiology clinic. After history-taking and medication review to exclude possible central nervous system- or medication-related central sleep apnea, an overnight polysomnography study was performed, and CSR was identified. The morning serum MMP-2, MMP-9, and BNP levels were determined using enzyme-linked immunosorbent assay and fluorescence immunoassay techniques. A positive airway pressure device was applied to 7 patients for 3 months. The serum MMP-2 and BNP levels were significantly higher in HFrEF patients with CSR than in patients without CSR. In addition, elevated serum MMP-2 levels correlated well with the severity of sleep apnea and intermittent hypoxia, which were represented as the apnea-hypopnea index and the oxygen desaturation index. No positive correlation was found between those markers and left ventricular ejection fraction. Finally, the treatment of sleep apnea with continuous positive airway pressure for 3 months tended to reduce the elevated serum MMP-2 levels. Higher serum MMP-2 and BNP levels were found in HFrEF patients with CSR. Elevated MMP-2 levels were correlated with the severity of sleep apnea and intermittent hypoxia. Chuang L-P, Pang J-HS, Lin S-W, etal. Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration. J Clin Sleep Med. 2022;18(5):1365-1373.

Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF

ObjectivesThis study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. BackgroundThrough inhibition of neprilysin, Sac/Val may increase BNP concentrations. MethodsIn an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. ResultsMedian (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [−30% to +41%]; P = 0.36) or week 12 (+1% [−36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by −30% (−50% to −8%) and −32% (−54% to −1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [−34% to +115%]), unchanged (+34% [−15% to +205%]), or increased (+57% [−12% to +14%]). ConclusionsIn this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.

Heart disease, as the most serious threat to human health globally, is responsible for rising mortality rates, largely due to lifestyle and diet. Unfortunately, the main problem for patients at high risk of heart disease is the validation of prognostic tests. To this end, the detection of cardiovascular biomarkers has been employed to obtain pathological and physiological information in order to improve prognosis and early-stage diagnosis of chronic heart failure. Short-term changes in B-type natriuretic peptide are known as a standard and important biomarker for diagnosis of heart failure. The most important problem for detection is low concentration and short half-life in the blood. The normal concentration of BNP in blood is less than 7 nM (25 pg/mL), which increases significantly to more than 80 pg/mL. Therefore, the development of new biosensors with better sensitivity, detection limit, and dynamic range than current commercial kits is urgently needed. This review classifies the biosensors designed for detection of BNP into electrochemical, optical, microfluidic, and lateral-flow immunoassay techniques. The review clearly demonstrates that a variety of immunoassay, aptasensor, enzymatic and catalytic nanomaterials, and fluorophores have been successfully employed for detection of BNP at low attomolar ranges. Dtection of B-type natriuretic peptide with biosensors.

Arginine Vasopressin as an Important Mediator of Fluctuations in the Serum Creatinine Concentration Under Decongestion Treatment in Heart Failure Patients.

Background: The mechanism underlying serum creatinine (SCr) fluctuations in heart failure (HF) patients remains unclear. This study examined mediators of SCr fluctuations under diuretic treatment in HF patients.Methods and Results: Data from 26 HF patients were analyzed. Clinical tests included measurement of peripheral blood, blood urea nitrogen, SCr, serum and urinary electrolytes, B-type natriuretic peptide (BNP), and plasma neurohormones. Among the 26 patients recovering from worsening HF, changes in SCr were negatively correlated with changes in serum Cl, and positively correlated with changes in plasma arginine vasopressin (AVP). According to the median change in SCr, patients were divided into high (range 0.16–0.79 mg/dL; n=13) and low (range −0.35 to 0.14 mg/dL; n=13) change groups. Plasma AVP concentrations after treatment decreased in the low SCr change group and increased in the high SCr change group (−1.28±2.8 vs. 2.14±4.4 pg/mL, respectively; P=0.027). In both groups, there was no change in plasma volume, plasma BNP and norepinephrine concentrations decreased, and plasma renin activity increased after treatment. Multivariate logistic regression analysis showed a tendency towards an independent association between an increase in SCr and an increase or no change in the plasma AVP after decongestion (odds ratio 4.44; 95% confidence interval 0.81–24.3; P=0.086).Conclusions: Plasma AVP appears to be a physiologically important mediator of SCr fluctuations under decongestion treatment in HF patients.

Pregnancy-specific Reference Intervals for BNP and NT-pro BNP-Changes in Natriuretic Peptides Related to Pregnancy.

ContextCardiac disease is the leading cause of maternal mortality in the UK, so accurate cardiovascular diagnoses in pregnancy are essential. BNP (B-type natriuretic peptide) and NT-pro BNP (N-terminal-pro BNP) are useful clinical tools for investigating suspected peripartum cardiomyopathy but, as the pregnancy-specific reference intervals are undefined, it is uncertain how they should be interpreted in pregnant women.ObjectivesTo define trimester-specific 95% reference intervals for BNP and NT-pro BNP in pregnancy.MethodsLongitudinal study of 260 healthy pregnant women, with sampling in each trimester.ResultsThe upper reference limit for NT-pro BNP was 200 pg/mL in the first and second trimesters, and 150 pg/mL in the third. Levels were significantly reduced in overweight women in the third trimester (P = .0001), which supports the partitioning of reference intervals by body mass index (BMI). The upper limit for BNP was 50 pg/mL, with no detectable trimester-related differences. Although other biomarkers (hemoglobin and platelets) fell throughout pregnancy, both natriuretic peptides were initially elevated before falling by the third trimester, suggesting that the observed changes in natriuretic peptides are driven by dynamic interplay between cardiac strain and progressive hemodilution. NT-pro BNP in the first trimester was inversely associated with neonatal birthweight at term (P = .011).ConclusionCardiac biomarkers have an important role for investigating suspected disease in high-risk pregnant women, but a robust assessment of the levels expected in healthy pregnant women is an essential prerequisite to their application in clinical practice. This study has defined trimester- and BMI-specific reference intervals for NT-pro BNP and BNP, which may improve how women with suspected cardiovascular disease are investigated in pregnancy.

Decongestion discriminates risk for one-year mortality in patients with improving renal function in acute heart failure.

Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion. We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a ≥20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a ≥40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m2 . IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction=0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality. Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF.

1104 B-Type natriuretic peptide as a predictor of hypertensive disease of pregnancy in maternal cardiac disease

To investigate changes in B-type natriuretic peptide (BNP) during pregnancy in women with congenital heart disease (CHD) and evaluate its utility as a predictor of adverse outcomes. Retrospective cohort study of singleton gestations with maternal CHD that delivered at a tertiary care center from March 2013 to August 2020 with at least one pregnancy BNP value. The primary outcomes were development of a composite adverse cardiovascular (CV) outcome, diagnosis of hypertensive (HTN) disease of pregnancy, and endorsement of CV symptoms. BNP values were categorized as less than or equal to or greater than 100 pg/mL, the threshold predictive of heart failure outside of pregnancy. Given lack of an established diagnostic threshold value in pregnancy, median, maximum, and trend of BNP values were obtained. Only BNP measurements collected prior to the development of an adverse outcome were evaluated. BNP values were compared with Chi-squared and Wilcoxon rank sum tests among those who did and did not develop an adverse outcome. 81 pregnancies with maternal CHD had at least one BNP measurement. 30 (37.0%) had a composite adverse CV outcome, 16 (19.8%) developed HTN disease of pregnancy, and 52 (64.2%) endorsed CV symptoms. BNP was not different for those who developed an adverse CV outcome (p=0.76) or endorsed CV symptoms (p=0.40). A BNP measurement above 100 pg/mL was associated with the development of HTN disease of pregnancy (p=0.01). The difference between minimum and maximum BNP values throughout pregnancy was higher with the development of HTN disease of pregnancy (p=0.03). A BNP less than or equal to 100 pg/mL has a negative predictive value of 96.1% for HTN disease of pregnancy in participants. In pregnancies complicated by maternal CHD, BNP greater than 100 pg/ml and increasing BNP over gestation is associated with the development of HTN disease of pregnancy but not adverse CV outcomes. Evaluation of BNP may be of clinical utility in the antepartum surveillance of pregnant women with cardiac disease, specifically when evaluating for HTN disease of pregnancy.