Baseline B-type Natriuretic Peptide Levels Research Articles

Impact of medical checkup parameters on major adverse cardiovascular events in the general Japanese population

Medical checkups play a role in the identification of individuals at increased cardiovascular risk. However, the impact of each medical examination parameter on the incidence of major adverse cardiovascular events (MACE) has not been intensively studied. Here we assessed the predictors of MACE among parameters examined during medical checkups in the general Japanese population. A total of 13,522 individuals (mean age, 52.8 ± 12.3 years) who participated in our medical checkup program from 2008 to 2015 were followed up for a median of 1,827 days with the endpoint of MACE. MACE included cardiovascular death, non-fatal myocardial infarction, angina, decompensated heart failure, stroke, and other cardiovascular events requiring hospitalization. Possible associations between MACE and baseline clinical test parameters were investigated. During follow-up, MACE occurred in 196 participants. Participants with hypertension, diabetes mellitus, dyslipidemia, or metabolic syndrome were at increased risk of MACE on the univariate analysis. Multivariate Cox hazard analysis demonstrated that male sex, age, systolic blood pressure, and baseline B-type natriuretic peptide level were independently correlated with future MACE after the adjustment for confounders; the impact of B-type natriuretic peptide was most prominent among the investigated variables. These results suggest that B-type natriuretic peptide level obtained during a medical checkup examination is an independent and strong predictor of MACE. The inclusion of BNP as part of medical checkup parameters may improve the ability to identify individuals at increased cardiovascular risk and prevent cardiovascular disease among them.

The Prognostic Value of B-Type Natriuretic Peptide in Patients With Cardiac Sarcoidosis Without Heart Failure: Insights From ILLUMINATE-CS.

Background The prognostic role of BNP (B-type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow-up period of 3.0 (interquartile range, 1.7-5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan-Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log-rank P=0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19-3.55]; P=0.010). Log-transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31-3.43]; P=0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN-CTR: UMIN000034974.

Stress-Delta B-Type Natriuretic Peptide Does Not Exclude ACS in the ED.

There are many detectable changes in circulating biomarkers in the setting of myocardial ischemia. We hypothesize that there are associated changes in circulating B-type natriuretic peptide (BNP) level after stress-induced myocardial ischemia, which can be used for emergency department (ED) acute coronary syndrome (ACS) risk stratification. In a prospective study, we enrolled 340 patients over the age of 30 receiving an exercise echocardiography stress test in an ED observational unit for suspected ACS. We collected blood samples at baseline and at 2 and 4 h post-stress test, measuring the relative and absolute changes (stress-delta) in plasma BNP concentrations. In addition, patients were contacted at 90 days and at 1 year posttest for a follow-up. We calculated the diagnostic test characteristics of stress-delta BNP for a composite outcome of ischemic imaging on stress echocardiogram, nonelective percutaneous coronary intervention, coronary artery bypass graft surgery, subsequent acute myocardial infarction, or cardiac death at 1 year via a logistic regression. We analyzed the 2-h BNP concentrations using an ANOVA model to adjust for the baseline BNP level. Baseline and 2-h post-stress BNP were both higher in the positive outcome group, but the stress-delta BNP was not. Stress-delta BNP had a sensitivity and specificity, respectively, of 53% and 76% at 2 h and 67% and 68% at 4 h. It was noted that patients with the composite outcome had a higher baseline BNP level. BNP stress-deltas are poor diagnostic means for ACS risk stratification, but resting BNP remains a promising prognostic tool for ED patients with suspected ACS.

Clinical Significance of B-Type Natriuretic Peptide Levels at 3 Months after Atrial Fibrillation Ablation.

The role of B-type natriuretic peptide (BNP) levels as a predictor of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation remains unclear. In this study, we investigated the association of BNP levels before and 3 months after ablation with the risk of AR. A total of 234 patients undergoing their first session of AF ablation were included (68% male, mean age of 69 years). The cut-off value for discriminating AR was determined based on the maximum value of the area under the receiver operating characteristic (ROC) curve. The impact of BNP levels on AR was evaluated using Cox regression analysis. ROC curve analysis showed that the area under the curve for BNP at 3 months after the procedure was larger (0.714) compared to BNP levels before ablation (0.593). Elevated levels of BNP 3 months after the procedure (>40.5 pg/mL, n = 96) was associated with a higher risk of AR compared to those without elevated levels (34.4% vs. 10.9%, p < 0.01). Multivariate Cox regression analysis revealed that elevated BNP levels were associated with an increased risk of AR (hazard ratio 2.43; p = 0.014). Elevated BNP levels 3 months after AF ablation were a significant prognostic factor in AR, while baseline BNP levels were not.

Abstract 14866: Plasma B-type Natriuretic Peptide Levels Are Associated With Future Cardiovascular Events in Patients With Type 2 Diabetes Mellitus Without Known Cardiovascular Disease

Introduction: B-type natriuretic peptide (BNP) is known to predict future cardiovascular (CV) events in patients with known CV disease. However, these associations have not been investigated in patients with type 2 diabetes mellitus (T2DM) without known CV disease. We investigated whether BNP levels are associated with CV events among T2DM patients without known CV disease using the dataset of EMPATHY study. Methods and Results: The EMPATHY was a randomized controlled trial of intensive statin therapy in T2DM patients without known CV disease. CV events were defined as composite of cardiac (acute coronary syndrome and coronary revascularization [excluding heart failure]), cerebral, and vascular events. A total of 4704 patients without CV events or death during the first 12 months were included and 114 CV events occurred during a median follow-up of 37.8 months. The patients were divided based on quartile of baseline BNP levels (Q1: &lt;7.4, Q2: 7.4-14.8, Q3: 14.8-28.7, Q4: ≥28.7 [pg/mL]). Compared to the lowest quartile of BNP, only the highest quartile was associated with increased risk for CV events after adjustment (HR 2.96, 95% CI 1.29-6.79, p=0.010). Using this highest quartile cutoff, we categorized BNP &lt;28.7 pg/mL as low BNP and BNP ≥28.7 pg/mL as high BNP. Compared to patients with low BNP, the adjusted HRs for CV events were 2.12 (95% CI 1.35-3.34, p=0.001) in patients with high BNP at baseline and 2.64 (95% CI 1.67-4.17, p&lt;0.001) in those with high BNP at 12 months. In analysis using serial measurement, patients who had repeatedly high BNP or had low BNP at baseline and high BNP at 12 months were in significantly higher risk for CV events compared to those who had repeatedly low BNP (HR 3.28, 95% CI 1.90-5.66, p&lt;0.001 or HR 2.65, 95% CI 1.44-4.87, p=0.002, respectively), whereas those who had high BNP at baseline and low BNP at 12 months were not (HR 1.99, 95% CI 0.90-4.39, p=0.089). Conclusion: Increased BNP levels were associated with higher risk of CV events (excluding heart failure) in T2DM patients without known CV disease. HR for CV events was greater in patients with repeatedly high BNP than in those with high BNP at only one of the two measurements, suggesting that serial BNP measurement may be more useful for predicting future CV events in T2DM patients.

Evaluating the diagnostic and prognostic value of cardiac biomarkers for heart disease and major adverse cardiac events in patients with muscular dystrophy

Abstract Background Heart disease is recognized as the leading cause of morbidity and mortality in patients with muscular dystrophy (MD). Validating and testing for heart disease in this vulnerable cohort of patients will allow for early cardiac interventions, monitoring, and improved outcomes. Purpose To evaluate the diagnostic and prognostic value of baseline B-type natriuretic peptide (BNP) and high-sensitive troponin I (hsTnI) for cardiomyopathy and major adverse cardiac events (MACE), respectively, in patients with MD. Methods A prospective cohort study was conducted at our clinic following 117 patients [median age, 42 years (interquartile range [IQR], 26–50); 49 (41.88%) women] diagnosed with a dystrophinopathy, limb-girdle MD, type 1 myotonic dystrophy, or facioscapulohumeral MD. Patients received multifaceted care as part of the multidisciplinary pathway allowing for a complete assessment of patient clinical status. Cardiac assessment included physical exam and electrocardiogram as well as subsequent echocardiogram and cardiac magnetic resonance imaging. Receiver operating curves and corresponding Youden's Indices were utilized to assess the diagnostic abilities of the biomarkers and for subsequent derivation of hazard ratios (adjusted by patient demographics and diagnosis of cardiomyopathy and respiratory disease) for incidence of MACE (defined as the composite of arrhythmia, device implantation, cardiac-related hospitalization, incident heart failure, and cardiac-related mortality). Results At baseline, 35 (29.91%) patients were diagnosed with a cardiomyopathy. B-type natriuretic peptide was an effective diagnostic marker of cardiomyopathy with an area under the curve (AUC) of 0.64 (95% confidence interval (CI), 0.52–0.76; P=0.017), as was hsTnI (AUC, 0.69 [95% CI, 0.58–0.80]; P=0.001). In combination, BNP and hsTnI showed additive diagnostic ability for cardiomyopathy [AUC: 0.72 (95% CI, 0.61–0.83); P&amp;lt;0.001]. Over a median follow-up period of 2.09 years (IQR, 1.17–2.81) there were 36 confirmed MACE. Patients were stratified based on cutoff values of BNP and hsTnI established a priori defined as 30.50 pg/mL and 7.61 ng/L, respectively. Patients with BNP levels above the cutoff value had a 4.76-fold (95% CI, 2.13–10.65; P&amp;lt;0.001) greater risk of MACE than patients with BNP levels below. Patients with hsTnI levels above the cutoff value had a 3.98-fold (95% CI, 1.96–8.12; P&amp;lt;0.001) greater risk of MACE than patients with hsTnI levels below. Importantly, patients with biomarker levels above both cutoff values had a 5.28-fold (95% CI, 2.42–11.51; P&amp;lt;0.001) greater risk of MACE than patients with biomarker levels below both cutoffs. Conclusion Our study demonstrates that by including measures of BNP and hsTnI as part of a comprehensive cardiac assessment, the diagnosis of cardiomyopathy and prognostication of MACE can be improved in patients with MD. Risk Stratification of MACE Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Hospital Foundation, University of Alberta

Subclinical elevated B-type Natriuretic Peptide (BNP) indicates endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals

AimsBaseline elevated B-type Natriuretic Peptide (BNP) has been found in high altitude pulmonary edema susceptible population. Exaggerated pulmonary vascular response to hypoxia may be related to endothelial dysfunction in hypoxia susceptible. We hypothesize that baseline BNP levels can predict hypoxia susceptibility in healthy individuals. Main methodsThe pulmonary vascular response to hypoxia was compared in 35 male healthy individuals divided into two groups based on BNP levels (Group 1 ≤ 15 and Group 2 > 15 pg/ml). Acute normobaric hypoxia was administered to both the groups, to confirm hypoxia susceptibility in Group 2. Key findingsUnlike Group 1, Group 2 had elevated post hypoxia BNP levels (26 vs 33.5 pg/ml, p = 0.002) while pulmonary artery pressure was comparable. A negative correlation with tissue oxygen consumption (delta pO2) and compartmental fluid shift was seen in Group 1 only. Endothelial dysfunction in Group 2 resulted in reduced vascular compliance leading to elevation of mean blood pressure on acute hypoxia exposure. BNP showed a positive correlation with endothelial dysfunction in Group 2 and has been linked to pre-diabetic disorder (HbA1c 6 ± 0.44%) and may additionally represent a lower cross-sectional area of vascular bed related to vascular remodeling mediated by chronic hypoxia. SignificanceHypoxia susceptibility in healthy individuals may be related to endothelial dysfunction that limits vascular compliance during hypoxic stress. BNP level showed positive correlation with HbA1c (r = 0.49, p = 0.04) and negative correlation with delta pO2 (r = −0.52, p = 0.04) can predict reduced microvascular compliance due to endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals. BNP levels≤15 pg/ml at sea level is indicative of hypoxia resistance.

Prognostic Implications of Baseline B-type Natriuretic Peptide in Patients Undergoing Transcatheter Aortic Valve Implantation

B-type natriuretic peptide (BNP) levels have been shown to predict outcomes in surgical aortic valve replacement patients. BNP levels have not been well studied in patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study is to define the utility of baseline BNP levels in predicting short-term outcomes after TAVI. In this retrospective, observational, study from 2012 to 2019, we reviewed data on 1297 low-risk, intermediate-risk and high-risk patients who underwent TAVI. Patients were dichotomized into those with baseline BNP levels above or below 500 pg/ml. Our primary outcome was a composite of inpatient stroke and death. Our secondary outcome was a composite of 30-day stroke, death and readmission. There were 975 patients with a baseline BNP level of <500 pg/ml and of those, 2% had our primary composite outcome and 13% of patients had our secondary composite outcome. There were 322 patients with a baseline BNP level of ≥500 pg/ml and of those, 6% had our primary composite outcome and 19% of patients had our secondary composite outcome. Those with a baseline BNP level ≥500 pg/ml were 3.47 times more likely (confidence of interval [CI] 1.727, 6.993, p = 0.0005) to have our primary composite outcome and were 1.72 times more likely (CI 1.186, 2.506, p = 0.0043) to have our secondary composite outcome. In conclusion, after adjustments for discrepant baseline characteristics, baseline BNP levels were independently predictive of a composite of inpatient stroke or death and a composite of 30-day stroke, death or readmission after TAVI. Those low, intermediate and high-risk patients whose baseline BNP is ≥500 pg/ml may ultimately require closer post-TAVI monitoring.

Randomized Clinical Trial on the Effect of Bardoxolone Methyl on GFR in Diabetic Kidney Disease Patients (TSUBAKI Study)

IntroductionBardoxolone methyl significantly increases estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD). However, the phase 3 study, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: the Occurrence of Renal Events (BEACON), was terminated prematurely because bardoxolone methyl increased the risk for early-onset fluid overload in patients with identifiable risk factors for heart failure (elevated baseline B-type natriuretic peptide levels >200 pg/ml and prior history of hospitalization for heart failure). The Phase 2 Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) study aimed to determine if patients without risk factors can mitigate the risk for fluid overload and whether changes in eGFR with bardoxolone methyl reflect true increases in GFR.MethodsThis phase 2, randomized, multicenter, double-blind, placebo-controlled study enrolled patients with type 2 diabetes and stage 3–4 CKD. Patients were randomized 1:1 to bardoxolone methyl (n = 41) or placebo (n = 41) (cohort G3), or 2:1 to bardoxolone methyl (n = 24) or placebo (n = 14) (cohort G4), administered orally once daily for 16 weeks using a dose-titration scheme. The primary efficacy endpoint was change from baseline in GFR measured by inulin clearance at week 16 in the cohort G3.ResultsA total of 40 patients were evaluated for the prespecified primary efficacy analysis. Mean change (95% confidence interval [CI]) from baseline in GFR was 5.95 (2.29 to 9.60) and −0.69 (−3.83 to 2.45) ml/min per 1.73 m2 for patients randomized to bardoxolone methyl and placebo, respectively, with a significant intergroup difference of 6.64 ml/min per 1.73 m2 (P = 0.008). Increases in the albumin/creatinine ratio were observed in the bardoxolone methyl group vs the placebo group. The most common adverse events (≥15% in either group) were viral upper respiratory tract infection, increased alanine aminotransferase, increased aspartate aminotransferase, increased γ-glutamyltransferase, and constipation. Peripheral edema was reported by 4 patients receiving bardoxolone methyl and by 1 patient receiving placebo; all events were mild and self-limiting. No patient died or experienced heart failure. The study discontinuation rate was higher in the bardoxolone methyl group (cohort G3, n = 8; cohort G4, n = 7) than the placebo group (cohort G3, n = 1; cohort G4, n = 0).ConclusionBardoxolone methyl significantly increased measured GFR, and further investigation is ongoing to evaluate whether it provides clinical benefit without major safety concerns in selected patients with CKD.

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus

Plasma B-type natriuretic peptide (BNP) is a useful marker for diagnosis of hemodynamically significant PDA (hsPDA) and serial BNP measurement is also valuable for monitoring treatment response. This retrospective study was performed to evaluate whether plasma BNP level can predict treatment response to ibuprofen in preterm infants born at <30 weeks of gestation with hsPDA. Plasma BNP was measured before (baseline) and 12 to 24 h after (post-treatment) completion of the first (IBU1) and second (IBU2) course of ibuprofen. We compared the BNP levels of responders (closed or insignificant PDA) with those of non-responders (hsPDA requiring further pharmacologic or surgical closure) to each course of ibuprofen. The treatment response rates for IBU1 (n = 92) and IBU2 (n = 19) were 74% and 26%, respectively. In IBU1, non-responders had lower gestational age and birth weight than responders (both, P = 0.004), while in IBU2, non-responders had lower birth weight (P = 0.014) and platelet counts (P = 0.005) than responders; however, baseline BNP levels did not differ significantly between responders and non-responders in either IBU1 (median 1,434 vs. 1,750 pg/mL) or IBU2 (415 vs. 596 pg/mL). Post-treatment BNP was a useful marker for monitoring treatment efficacy of IBU1 and IBU2 for hsPDA with a cut-off value of 331 pg/mL (P < 0.001) and 423 pg/mL(P < 0.010), respectively. We did not identify a cut-off baseline BNP level that could predict treatment response to ibuprofen in preterm infants with hsPDA.

Serum ST2 and hospitalization rates in Caucasian and African American outpatients with heart failure

BackgroundLimited data exist on the association between circulating suppression of tumorigenicity 2 (ST2) and recurrent hospitalizations and emergency department (ED) encounters in outpatients with heart failure (HF). In addition, data on ST2 in African American patients with HF are scarce. MethodsWe evaluated 307 outpatients with HF (age, 57 ± 12 years; 64.2% men; 51.5% Caucasian, 45.6% African American; median ejection fraction, 35%; ischemic etiology, 41.4%). Median ST2 was 37.8 ng/mL (29.6–51.4). ResultsAfter a median of 3.1 years, there were 584 hospitalizations (224 for HF) and 335 ED visits (80 for HF). Patients (N = 176; 57.3%) with elevated (>35 ng/mL) ST2 had 2-fold higher hospitalization rates in adjusted models (rate ratio [RR] 1.97; 95% CI 1.38–2.82; P < 0.001), driven by 3.5-fold higher HF hospitalization rates (adjusted RR 3.56; 95% CI 1.69–7.49; P < 0.001). These associations persisted after adjusting for baseline B-type natriuretic peptide levels. Findings were similar for elevated ST2 and ED visit rates. Elevated ST2 was associated with the composite of death or HF hospitalization (109 patients; 3-year estimate: 35.4%); risk was 5-fold higher in the first 6 months but declined gradually. The higher hospitalization rates and composite endpoint risk associated with elevated ST2 was similar in African Americans and Caucasians. In landmark analyses in a subset of patients, 6-month (N = 112) and 12-month (N = 149) changes in ST2 levels from baseline added prognostic information. ConclusionsElevated ST2 in outpatients with HF portends higher healthcare resources utilization and higher risk for accelerated disease progression, regardless of race, especially in the first 6 months.

Increasing Age Hinders the Decline in B-Type Natriuretic Peptide Following Parathyroidectomy in Dialysis Patients

Parathyroidectomy has beneficial effects on all-cause and cardiovascular mortality in patients with uncontrolled hyperparathyroidism. B-Type natriuretic peptide (BNP) correlates with the severity of heart failure. We aimed to investigate whether parathyroidectomy modulates the BNP levels in dialysis patients. Patients who underwent surgical intervention for hyperparathyroidism were included. The serum BNP levels were determined before parathyroidectomy and during follow-up. The preoperative and postoperative BNP levels were 499±561 and 453±442 pg/ml, respectively (p=0.82). The baseline BNP level was positively correlated with weakness and headache, but not biochemical parameters. In multivariate analysis, age (odds ratio=0.837) and preoperative symptom score (odds ratio=0.935) were independent predictors for the postoperative decline in BNP levels Conclusion: The serum BNP levels may increase or decrease after parathyroidectomy. Younger age and lower symptom burden are associated with decline in BNP levels.

Dynamics and prognostic value of B-type natriuretic peptide in left ventricular assist device recipients.

The prognostic utility of B-type natriuretic peptide (BNP) in heart failure is well recognized. Previous studies demonstrated that BNP levels decrease after left ventricular assist device (LVAD) implantation. We sought to investigate the predictive value of baseline and changes in BNP levels in LVAD recipients. BNP was measured in baseline and follow-up plasma samples from consecutive patients receiving a continuous-flow LVAD from 2010 through 2016. Absolute values and changes from baseline were related to clinical outcomes. Median BNP at baseline was 885 [interquartile range (IQR): 450-1,624] pg/mL, decreasing to 289 (IQR: 154-534) pg/mL at 90 days after LVAD implantation. Cox regression analysis revealed that higher baseline and follow-up BNP levels were not associated with increased risk of death at 180 days (P=0.12 and P=0.32, respectively). In the univariate analysis 90-day BNP, but not baseline BNP, was significantly associated with the combined death/hospitalization outcome 180 days after LVAD implantation [hazard ratio (HR) 1.03, 95% CI: 1.01-1.06; P=0.006]. This significance was not preserved after adjusting for multiple covariates (HR 1.01, 95% CI: 0.98-1.04; P=0.62). At 90 days, there was no BNP lowering in 20.6% of subjects. This was not associated with higher risk for death or the composite of death/hospitalization (P=0.11 and P=0.06 respectively). BNP absolute levels and changes from baseline are not independently associated with clinical outcomes after LVAD-implantation. These findings suggest an impaired prognostic performance of BNP after LVAD implantation.

B-type natriuretic peptide: Usefulness in the management of critically-ill neonates.

B-type natriuretic peptide (BNP) is responsible for changes in the heart organogenesis and is associated with transition to extrauterine life. In the first week of life, BNP levels are high and return to normal with the physiological loss in weight. High BNP levels are associated with different conditions. To establish the relationship between BNP levels and criticality and the short-term clinical course among patients hospitalized in the neonatal intensive care unit. Observational and analytical study conducted in a prospective cohort. Criticality was defined as a requirement for assisted mechanical ventilation with a fraction of inspired oxygen of more than 50% and/or inotropes. Two blood samples were collected 72 hours apart. Seventy-three patients were included in the study. Depending on their clinical course on day 7, they were divided into 2 groups: patients with a good clinical course or a persistent, severe clinical course. The median baseline BNP level was similar in both groups (p: 0.15). The median BNP level at 72 hours was higher among patients with a persistent, severe clinical course (p: 0.005). The difference between both BNP values was calculated (ΔBNP: BNP level at 72 hours - BNP level at 0 hours). The ΔBNP was positive among patients with a persistent, severe clinical course (X= 1260 pg/mL; range: 426-2094) and negative in the group with a good clinical course (X= -967 pg/mL; range: -1656/-278) (p: 0.0002); sensitivity: 87%; specificity: 86%; positive predictive value: 74%; and negative predictive value: 93%. In this group of patients, the delta-BNP value reflected the short-term clinical course.

Markers as predictors of clinical worsening in pulmonary arterial hypertension

Various biomarkers have been demonstrated to represent prognostic markers in adult patients with pulmonary arterial hypertension (PAH), however few data are available on their value in pediatric population. We aimed to assess the role of serum and imaging markers, such as B-type natriuretic peptide (BNP) and echocardiography-derived parameters characterizing right ventricular function and hemodynamics, in predicting clinical worsening in pediatric PAH. In 28 pediatric patients with PAH (group 1 - patients clinically stable at 12months “no clinical worsening”, n=14, 50%; group 2 - patients with clinical worsening at 12months “clinical worsening”, n=14, 50%), BNP, echocardiographic parameters (at baseline, 6months and 12months), World Health Organization functional class (“WHO FC”), 6-minute walk test (6MWT) were correlated with clinical status at 12months. Baseline BNP levels were significantly higher in group 2 vs group 1 (47.19pg/mL vs 16.97pg/mL, p=0.03) and presented an inverse non-significant correlation with 6MWT at baseline, 6 and 12months. BNP significantly increased at 12months in group 2 (118.03pg/mL vs 12.97pg/mL, p<0.0001). ROC-analysis identified a baseline BNP cut-off value of 59.5pg/mL with an 85.71% specificity (with an AUC of 0.71) for defining the group of patients at risk of clinical worsening from the group of patients who may have a stable clinical evolution. A BNP value >59.5pg/mL can serve as an indicator of high risk for future clinical deterioration in pediatric PAH.

DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes

BackgroundUse of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD).MethodsB-type natriuretic peptide and NT-proBNP were measured using commercially available clinical-grade immune-assays at baseline and at the end of a 4-day treatment with placebo and linagliptin. Changes from baseline during each treatment arm, as well as placebo-subtracted effects of linagliptin on BNP and NT-proBNP were calculated.Results46 patients completed the study, 18 of whom were affected by CKD. Baseline BNP and NT-proBNP levels increased with age, were elevated in CKD patients, and inversely correlated with estimated glomerular filtration rate. No significant change was detected in BNP and NT-proBNP levels after treatment with linagliptin or placebo in patients with or without CKD. Only in CKD patients the placebo-subtracted effect of linagliptin indicated a significant reduction in NT-proBNP levels, but this finding was not statistically robust.ConclusionsAcute treatment with a DPP-4i exerts no clinically-meaningful effects on BNP and NT-proBNP. As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology.Trial registration NCT01617824

The Impact of Biochemical Markers on Major Adverse Cardiovascular Events and Contralateral Carotid Artery Stenosis Progression Following Carotid Interventions

To determine if elevated preintervention high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) levels associate with major adverse cardiovascular events (MACE) or disease progression after carotid revascularization. We retrospectively examined patients receiving elective carotid endarterectomy (CEA) or carotid artery stenting (CAS) at our institution from 2007 to 2014. All included patients had preintervention hsCRP and BNP levels. Examined outcomes of interest included contralateral carotid disease progression (increased stenosis or need for revascularization) and MACE (composite of death, stroke, myocardial infarction, need for coronary artery bypass graft or percutaneous coronary intervention) at 3years after procedure. The relationship between baseline hsCRP and BNP levels and time to event was examined by univariate and multivariate Cox proportional hazard regression analyses. A total of 248 patients were included in the analysis (mean age: 68±10years), with 14% receiving CAS and 86% CEA. A total of 61 patients (25%) had 1 or more MACE by 3years. Elevated hsCRP (>3mg/L) trended toward associating with MACE but failed to reach significance (hazard ratio [HR]: 1.6 [1.0-2.7], P=0.07). Multivariate analysis found that elevated BNP (>100pg/mL, HR: 2.2 [1.3-3.7], P=0.002) and diabetes mellitus (HR: 1.9 [1.2-3.2], P=0.01) predicted MACE. Having elevated preprocedural levels of both hsCRP and BNP significantly increased patients' likelihood of experiencing MACE (HR: 3.4 [1.6-7.1], P=0.001). About 175 patients received contralateral carotid imaging postprocedure and of those patients, 31 (18%) experienced stenosis progression and/or revascularization within 3years. However, neither elevated hsCRP (HR: 1.2 [0.6-2.3], P=0.68) nor BNP (HR: 1.1 [0.5-2.5], P=0.88) associated with disease progression. BNP elevation at the time of carotid intervention is associated with MACE in long-term follow-up. hsCRP does not appear to correlate with either disease progression of the contralateral artery or MACE.

B-type natriuretic peptide levels in patients with pericardial effusion undergoing pericardiocentesis

ObjectivesPericardial effusion is characterized by progressive accumulation of fluid within the pericardial space, resulting in increased intra-pericardial pressure and compression of the heart. As B-type natriuretic peptide (BNP) is secreted by the ventricles in response to increased myocardial stretch, we hypothesized that pericardial effusion, as well as its resolution, might influence BNP plasma levels. MethodsWe prospectively measured, in 146 consecutive patients with pericardial effusion, BNP plasma levels at baseline, soon after, and 24h after pericardiocentesis. A scoring system based on 7 clinical and echocardiographic parameters was developed, and patients were classified according to the number of variables as having low (0–2), intermediate (3–4), or high (5–7) severity score. ResultsOut of the 146 patients, 42 (29%) had normal values (<100pg/ml), whereas 104 (71%) had high BNP values at baseline. In the whole population, baseline BNP levels significantly decreased as the severity score increased (r=−0.21; P=0.01). 24h after pericardiocentesis, a significant increase in BNP was observed in patients with intermediate (P=0.004) score and with high (P<0.001) severity score; no increase occurred in low score patients (P=0.56). The higher was the severity score, the steeper was the increase in BNP through the three time-points considered (P=0.04). ConclusionsThe results of the present study show that BNP plasma levels are suppressed in the presence of severe pericardial effusion, and that they rise after pericardiocentesis. Future studies should investigate the role of BNP in assisting clinicians in the decision-making process of pericardial fluid drainage.

Association Between Baseline Natriuretic Peptides and Atrial Fibrillation Recurrence After Catheter Ablation.

Natriuretic peptides like B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) are reported to be increased in atrial fibrillation (AF) patients. However, the prognostic roles of BNP and NT-pro BNP in post-ablation AF recurrence remain inconclusive. We performed this meta-analysis to investigate the potential role of baseline natriuretic peptides in predicting AF recurrence after catheter ablation.Electronic databases were searched for studies that evaluated the potential relationship between AF recurrence and baseline BNP or NT-pro BNP levels. The pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to quantify differences in BNP or NT-pro BNP levels between patients with and without AF recurrence.Ten studies on BNP and 8 studies on NT-pro BNP were included, in which 411 of 1300 patients and 256 of 846 patients experienced AF recurrence, respectively. Overall, the pooled SMD of studies on BNP was 0.55 (95% CI: 0.260.84, P < 0.001) while the pooled SMD of studies on NT-pro BNP was 0.96 (95% CI: 0.62-1.30, P < 0.0001). Meta-regression was conducted by AF type, AF duration, follow-up period, left atrial dimension (LAD), and concomitant heart failure, after which subgroup analysis demonstrated only follow-up period (3 months or > 3 months) in the NT-pro BNP group might account for the heterogeneity. Sensitivity analyses indicated both the results were stable.Meta-analysis of current eligible studies suggested that both increased baseline BNP and NT-pro BNP levels are associated with greater risk of AF recurrence after catheter ablation, which could be biomarkers for predicting AF recurrence.

Interrelationship between the Myocardial Mass, Fibrosis, BNP, and Clinical Outcomes in Hypertrophic Cardiomyopathy.

Objective Increased left ventricular mass (LVM) and LV fibrosis mass (LVFM) are characteristics of hypertrophic cardiomyopathy (HCM). Additionally, a substantial increase in the plasma B-type natriuretic peptide (BNP) level is observed. Therefore, we investigated the interrelationship and clinical significances of these parameters in a HCM cohort that underwent cardiac MRI (CMR). Methods Patients with HCM (n=109) receiving regular outpatient treatment underwent CMR and follow-up through 2015 from CMR examinations. The clinical outcome measures were all-cause mortality, admission for worsening heart failure, and ventricular tachycardia/fibrillation. Results The baseline body mass index (BMI), LV outflow tract (LVOT) obstruction, New York Heart Association (NYHA) class, and increased left atrial dimension (LAD) index were associated with the plasma BNP level. In the CMR analysis, LVM and LVFM indices significantly correlated with the BNP level (r=0.422 and 0.368, respectively), which were independent determinants according to a multivariate analysis (p=0.009 and 0.023, respectively). A Kaplan-Meier analysis during a median follow-up of 19.4 months showed that the baseline LVM or LVFM index was not associated with the clinical outcomes. However, the baseline BNP level was significantly associated with them (p<0.001). In addition, a multivariate Cox proportional hazard analysis showed that plasma BNP was an independent predictor for the clinical outcomes after adjusting for age, sex, LVM, and LVFM. Conclusion The LVM and LVFM are determinants of the BNP level independent of the BMI, LVOT obstruction, LAD, and NYHA class in patients with HCM. However, plasma BNP may be a more sensitive integrated-marker for the clinical outcomes than LVM or LVFM.