Baseline B-type Natriuretic Peptide Research Articles

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.

P4666Higher BNP levels after transcatheter aortic valve implantation are associated with increased mortality and hospitalizations

Abstract Background Among patients with aortic stenosis (AS), the adverse association between increased B-type natriuretic peptide (BNP) levels and worse clinical outcomes, including mortality and hospitalization after valve replacement, has been demonstrated. However, little attention has been paid to the clinical consequences of BNP levels after valve replacement, which may have implications for medical therapy prescribed after the procedure. Purpose Evaluate the association between BNP levels after transcatheter aortic valve implantation (TAVI) and subsequent mortality and hospitalizations. Methods Among intermediate, high, and extreme risk patients with severe symptomatic AS who received TAVI for native valve AS in the PARTNER II and S3 clinical trials or registries, we included 3260 patients who had BNP measured at baseline. Patients from sites which measured NTproBNP were excluded. To account for factors that influence BNP levels, we developed a regression equation–including age, sex, BMI, creatinine, study site, and the upper limit of normal of the BNP assay used for a given measurement–to determine expected BNP. BNP ratio was determined pre-TAVR and at discharge, 30 days, and 1 year and calculated as the actual BNP/expected BNP. Using a landmark approach, the relationships between (1) BNP ratio at 30 days or (2) delta BNP ratio between discharge and 30 days and subsequent outcomes between 30 days and 1 year were assessed. The primary outcome was a composite of cardiovascular (CV) mortality or hospitalization. Adjustment was made for 20 baseline and post-procedural factors known to influence outcomes. Results Higher BNP ratio at 30 days was associated with higher CV mortality or hospitalization between 30 days and 1 year (adjusted hazard ratio [aHR] 1.07 per increase of 1 in the BNP ratio, 95% CI 1.04–1.10, p&lt;0.001), whereas baseline BNP ratio was not (p=0.38). A similar relationship was shown for the components of this composite: CV mortality (aHR 1.08, 95% CI 1.04–1.12, p&lt;0.001) and hospitalizations (aHR 1.04, 95% CI 1.01–1.08, p=0.01). Adjusted for discharge BNP ratio and other factors, a greater decrease in BNP ratio between discharge and 30 days was also associated with lower CV mortality or hospitalization between 30 days and 1 year (aHR 0.95 per decrease of 1 in the BNP ratio, 95% CI 0.92–0.99, p=0.006). Similar relationships were observed for all-cause mortality and when examining the relationship between 1 year BNP ratio and outcomes between 1 and 2 years. Conclusion Higher BNP ratio after TAVI is associated with higher subsequent all-cause and CV mortality and hospitalizations, whereas baseline BNP ratio was not. Greater decrease in BNP ratio between discharge and 30 days is associated with better outcomes. Further investigation is warranted to understand these findings and determine whether intensification of medical therapy to decrease BNP after TAVR may improve patient outcomes. Acknowledgement/Funding The PARTNER 2 Trial was funded by Edwards Lifesciences

B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease

BackgroundRisk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust ‘real-world’ evidence for their use.MethodsProspective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression.ResultsFive hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45–3.19; p = 0.0001) and 1.27 for composite events (1.04–1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease.ConclusionsConventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management.Trial registrationClinicaltrials.gov, NCT00403351 Registered on 22 November 2006

LOW AND ELEVATED B-TYPE NATRIURETIC PEPTIDE LEVELS ARE ASSOCIATED WITH INCREASED MORTALITY IN PATIENTS WITH PRESERVED EJECTION FRACTION UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT: FROM THE PARTNER 2 TRIAL AND REGISTRIES

B-type natriuretic peptide (BNP) is secreted during adaptive response to cardiac damage. We assessed association between baseline BNP and outcomes in patients with symptomatic severe aortic stenosis (AS) and left ventricular ejection fraction (LVEF) ≥50% undergoing transcatheter aortic valve

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.

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.

B-type natriuretic peptide is associated with remodeling and exercise capacity after transcatheter aortic valve replacement for aortic stenosis.

BackgroundWe aimed to assess longitudinal changes of B‐type natriuretic peptide (BNP) in aortic stenosis (AS) patients treated by transcatheter aortic valve replacement (TAVR).MethodsFrom our TAVR database, we identified 193 consecutive patients with severe symptomatic AS who underwent TAVR and were prospectively followed using serial BNP levels and echocardiography. Patients were divided into subgroups according to type of left ventricular (LV) remodeling as having normal LV mass and relative wall thickness, or showing concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH).ResultsAt baseline, 30 patients (16%) had EH, 115 (60%) had CH, 37 (19%) had CR, and 11 (6%) had normal LV geometry. After TAVR, BNP decreased in the first 30 days, with further improvement during follow‐up. Patients with EH had higher BNP at baseline (P < 0.01) and a greater subsequent decrease (P < 0.001). During the median follow‐up of 1331 days (interquartile range: 632‐1678), 119 (62%) patients died. BNP showed a time‐dependent association with all‐cause mortality both in a univariable (hazards ratio [HR] 1.24, 95% confidence interval [CI]: 1.04‐1.47, P = 0.017), and in a multivariable model with Society of Thoracic Surgeons score and baseline BNP forced into the analysis (HR 1.32, 95% CI: 1.001‐1.73, P = 0.049). Elevated BNP was associated with a larger LV end‐diastolic volume index (P < 0.001) and shorter 6‐minute walk test distance (P = 0.013) throughout follow‐up.ConclusionIn patients with AS, BNP was associated with LV remodeling phenotypes and functional status before and after TAVR. Elevated BNP levels were associated with poor prognosis.

Clinical features and outcomes of patients with the cardio-renal syndrome admitting to a surgical intensive care unit

To investigate the clinical features and risk factors on outcomes of patients with cardio-renal syndrome (CRS) in surgical intensive care unit (SICU). The clinical data of the patients admitted to SICU of Peking University People's Hospital from January 1st 2017 to December 31st 2017 were analyzed retrospectively, including gender, age, severity of the disease, underlying diseases, type of CRS, precipitating factors of CRS, cardiac and renal function [cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), serum creatinine (SCr), glomerular filtration rate (eGFR)], outcomes [secondary outcomes, duration of mechanical ventilation, the length of ICU stay, the length of hospital stay, 28-day mortality and hospital mortality]. Patients were grouped according to CRS classification or hospitalization prognosis, the clinical features within different CRS types were analyzed, and risk factors on outcomes of the CRS patients were analysed by Logistic regression. 86 (7.3%) of the 1 172 patients during the study period had CRS. (1) CRS clinical features: CRS 1-5 type patients accounted for 24.4% (21 cases), 1.2% (1 case), 20.9% (18 cases), 1.2% (1 case) and 52.3% (45 cases) respectively, CRS type 1, 3 and 5 were the main types (i.e. acute cardiac and renal dysfunction), while type 5 CRS was the highest (i.e. organ dysfunction caused by simultaneous involvement of cardiac and renal functions secondary to systemic diseases was the most common). Baseline BNP (Z = 11.365, P = 0.023), SCr peak (Z = 13.405, P = 0.009) and baseline eGFR (F = 2.648, P = 0.037) were significantly different within the CRS 5 types. The basic cardiac function of type 1 CRS patients was significantly worse than that of type 3 and type 5 CRS patients [baseline BNP (μg/L): 434.2 (187.0, 1 252.0) vs. 154.9 (66.4, 272.5), 268.5 (124.1, 486.6), both P < 0.05]. The basic renal function of type 3 CRS patients was significantly worse than that of type 5 CRS patients [baseline eGFR (mL/min): 71.0±30.3 vs. 88.3±29.0, P < 0.05]. The severity of acute kidney injury (AKI) in type 3 CRS patients was significantly higher than that in type 1 and type 5 CRS patients [SCr peak (μmol/L): 285.0 (171.5, 420.6) vs. 143.0 (99.5, 213.5), 189.0 (105.5, 280.5), both P < 0.01]. There were no significant differences in gender, age, department, acute physiology and chronic health evaluation II (APACHE II), intraoperative blood loss, basic cTnI and SCr levels, BNP peak, AKI staging and prognostic indicators among patients with various types of CRS. (2) Death risk analysis: 43 (50%) of the 86 CRS patients died during the hospital stay. Compared with the survival patients, CRS death patients were older [years old: 72 (57, 80) vs. 62 (50, 73)] and had higher APACHE II score [22 (17, 29) vs. 18 (15, 21)], with higher proportion of cerebrovascular disease (9.3% vs. 0). Regarding to precipitating factors of CRS, sepsis/septic shock (41.9% vs. 18.6%) and surgery stress (9.3% vs. 0) were remarkably increased in death patients. Death patients had higher cTnI and SCr peak [cTnI peak (μg/L): 1.155 (0.192, 5.125) vs. 0.122 (0.045, 0.610), SCr peak (μmol/L): 208 (143, 295) vs. 146 (101, 289)] and also high proportion of AKI stage 3 (41.9% vs. 20.9%), higher rate of secondary infection (67.4% vs. 30.2%), prolonged duration of mechanical ventilation and the length of ICU stay [hours: 179 (61, 470) vs. 37 (7, 134); days: 10 (4, 24) vs. 5 (2, 11)], with statistically significant differences (all P < 0.05). Logistic regression analysis showed that the elderly [odds ratio (OR) = 1.053, 95% confidence interval (95%CI) = 1.003-1.094, P = 0.010], high APACHE II score (OR = 1.165, 95%CI = 1.057-1.285, P = 0.002), sepsis/septic shock (OR = 4.561, 95%CI = 1.351-15.391, P = 0.014) and AKI stage 3 (OR = 5.468, 95%CI = 1.457-20.530, P = 0.012) were independent risk factors for hospital death in CRS patients. Surgical ICU patients with CRS are characterized by acute cardiac and renal dysfunction. CRS type 5 is the most common and has a high fatality rate. Age, severity of illness, sepsis/septic shock and AKI stage 3 are independent risk factors of death.

Predictors of early and delayed recovery in peripartum cardiomyopathy: a prospective study of 52 Patients

Background: Predictors of early or delayed recovery are unclear in peripartum cardiomyopathy (PPCM). Therefore, we aimed to assess the prognostic value of serial assessment of clinical, echocardiographic, and biochemical markers in patients with PPCM.Methods: Fifty-two consecutive women with PPCM were enrolled in this prospective study. Each patient underwent transthoracic echocardiography, B-type natriuretic peptide (BNP) and C-reactive protein (CRP) measurement at admission, and every 3 months. Early recovery was defined as resolution of heart failure at 6 months postdiagnosis, delayed recovery was defined if the length of time required for recovery of left ventricular function was longer than 6 months, and persistent left ventricular dysfunction (PLVD) was defined as an ejection fraction of less than 50% at the end of follow-up.Results: Thirty patients (57.7%) recovered completely, 10 died (19.2%), and 12 (23.1%) had PLVD. There were no significant differences in baseline BNP and CRP values between patients who recovered completely and who did not recover. However, patients with complete recovery were more likely to have a higher left ventricular ejection fraction, smaller left ventricle end-systolic dimensions at baseline, and lower CRP and BNP levels at follow-up. Elevated levels of BNP and CRP on follow up at 3 and 6 months were associated with nonrecovery. Third and sixth month BNP values were significantly lower in patients with rapid recovery, compared to patients with delayed recovery. Bromocriptine therapy was also associated with early recovery.Conclusions: Persistent elevation of plasma CRP and BNP levels at follow-up portend a slower response or nonrecovery in patients with PPCM. Bromocriptine therapy was an independent predictor of early recovery.

B-type natriuretic peptide-guided therapy for heart failure (HF): a systematic review and meta-analysis of individual participant data (IPD) and aggregate data

BackgroundWe estimated the effectiveness of serial B-type natriuretic peptide (BNP) blood testing to guide up-titration of medication compared with symptom-guided up-titration of medication in patients with heart failure (HF).MethodsSystematic review and meta-analysis of randomised controlled trials (RCTs). We searched: MEDLINE (Ovid) 1950 to 9/06/2016; Embase (Ovid), 1980 to 2016 week 23; the Cochrane Library; ISI Web of Science (Citations Index and Conference Proceedings). The primary outcome was all-cause mortality; secondary outcomes were death related to HF, cardiovascular death, all-cause hospital admission, hospital admission for HF, adverse events, and quality of life. IPD were sought from all RCTs identified. Random-effects meta-analyses (two-stage) were used to estimate hazard ratios (HR) and confidence intervals (CIs) across RCTs, including HR estimates from published reports of studies that did not provide IPD. We estimated treatment-by-covariate interactions for age, gender, New York Heart Association (NYHA) class, HF type; diabetes status and baseline BNP subgroups. Dichotomous outcomes were analysed using random-effects odds ratio (OR) with 95% CI.ResultsWe identified 14 eligible RCTs, five providing IPD. BNP-guided therapy reduced the hazard of hospital admission for HF by 19% (13 RCTs, HR 0.81, 95% CI 0.68 to 0.98) but not all-cause mortality (13 RCTs; HR 0.87, 95% CI 0.75 to 1.01) or cardiovascular mortality (5 RCTs; OR 0.88, 95% CI 0.67 to 1.16). For all-cause mortality, there was a significant interaction between treatment strategy and age (p = 0.034, 11 RCTs; HR 0.70, 95% CI 0.53–0.92, patients < 75 years old and HR 1.07, 95% CI 0.84–1.37, patients ≥ 75 years old); ejection fraction (p = 0.026, 11 RCTs; HR 0.84, 95% CI 0.71–0.99, patients with heart failure with reduced ejection fraction (HFrEF); and HR 1.33, 95% CI 0.83–2.11, patients with heart failure with preserved ejection fraction (HFpEF)). Adverse events were significantly more frequent with BNP-guided therapy vs. symptom-guided therapy (5 RCTs; OR 1.29, 95% CI 1.04 to 1.60).ConclusionBNP-guided therapy did not reduce mortality but reduced HF hospitalisation. The overall quality of the evidence varied from low to very low. The relevance of these findings to unselected patients, particularly those managed by community generalists, are unclear.Systematic review registrationPROSPERO CRD42013005335

Prognostic Implications of Point-of-Care and Serial B-type Natriuretic Peptide Levels in Patients With Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) is a heterogenous disease with a variable clinical course. Predictors of long-term adverse cardiovascular events are needed. Our objectives were to determine the long-term prognostic value of a single and serial point of care (POC) B-type natriuretic-peptide (BNP) measurements in HC. One hundred and eleven ambulatory patients with HC (mean age 53 ± 16 years) were prospectively recruited over a 2-year period (2004 to 2006). A clinical assessment, comprehensive echocardiogram, and a POC BNP level was obtained at baseline and at a 1- to 2-year follow-up. They were subsequently followed for the occurrence of major adverse cardiac events (MACE). The median baseline BNP concentration was 114 pg/ml (range 5.3 to 1550 pg/ml). During a mean follow-up of 6.2 ± 3.4 years, 42 patients (38%) had a MACE. In a multivariable Cox model including clinical and echocardiographic predictors, logBNP (HR 4.30; 95% confidence interval 1.97 to 9.37, p <0.001) and left ventricualr ejection fraction (LVEF) (HR 0.96; 95% confidence interval 0.94 to 0.99, p = 0.011) remained significant predictors of MACE. Nested models demonstrated incremental prognostic value of logBNP for MACE (chi-square increased from 4.3 to 22.8, p <0.01) over clinical and echocardiographic factors. Patients with persistently elevated BNP (>100 pg/ml) at baseline and at the second visit were at a higher risk of developing MACE during follow-up (5-year MACE-free survival of 0.91 (SE 0.06) vs 0.45 (SE 0.09), p <0.001). In conclusion, POC BNP levels in patients with HC were predictive of long-term MACE and had independent and incremental value. Patients with persistently elevated BNP levels were at a higher risk of MACE.

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.

Biochemical markers in patients with open reconstructions with peripheral arterial disease.

The purpose of our study was to determine outcome differences as a function of baseline high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) levels in patients receiving lower extremity open reconstructions for the treatment of peripheral arterial occlusive disease. We retrospectively examined patients who underwent surgical reconstructions performed by a single operator during a seven-year time span who received preoperative hsCRP and BNP testing and post-procedure imaging. Outcomes of interest included major adverse limb events, a composite end point of target vessel revascularization, limb amputation, and disease progression, and major adverse cardiovascular events comprised of stroke, myocardial infarction, and death. A total of 89 limbs in 82 patients were included in analysis. Multivariate analysis demonstrated that higher hsCRP levels (>3.0 mg/L) trended toward, but failed to significantly associate with major adverse limb events at 24 months (hazard ratio: 2.2 [1.0-5.2], p = 0.06), however the use of a vein bypass conduit (vs. prosthetic reconstruction) significantly predicted major adverse limb events (hazard ratio: 3.2 [1.5-6.9], p < 0.01). Elevated BNP levels (>100 pg/ml), but not hsCRP, associated with major adverse cardiovascular events (hazard ratio: 3.5 [1.2-10.3], p = 0.03). Preoperative biochemical markers may assist in clinical decision making and stratifying patients regarding adverse events following open reconstructions.

Discharge BNP is a stronger predictor of 6-month mortality in acute heart failure compared with baseline BNP and admission-to-discharge percentage BNP reduction

IntroductionPrior studies found a significant relationship between admission B-type natriuretic peptide (BNP), discharge BNP and admission-to-discharge percentage BNP reduction and post-discharge mortality in acute heart failure (HF). MethodsThe ESCAPE trial data was utilized to identify which of these BNP parameters best predicts 6-month all-cause mortality. Results433 patients (mean age 56years, 74% men) included in our analysis had an admission BNP, discharge BNP and admission-to-discharge percentage BNP reduction of 1009pg/mL, 743pg/mL and −70%, respectively. There were significant differences between survivors and nonsurvivors with regards to admission BNP (P=0.001), discharge BNP (P=0.0001) and admission-to-discharge percentage BNP reduction (P=0.01). Discharge BNP had the highest area under the curve (AUC) for predicting mortality (AUC=0.702, P<0.001) followed by admission BNP (AUC=0.633, P=0.0006) then percentage BNP reduction (AUC=0.620, P=0.008). Comparison of AUC revealed a significant difference between discharge BNP and admission BNP (difference between areas 0.087, P=0.0223) and a trend towards significance when comparing AUC of discharge BNP with percentage BNP reduction (P=0.0637). Kaplan–Meier analysis showed a significant difference in survival according to optimum cutoff values of discharge BNP of 319pg/mL (log-rank P<0.001), admission BNP of 912pg/mL (P<0.001) and percentage BNP reduction of 7.71% (P=0.008). Cox-proportional-hazard-analysis revealed that discharge BNP is an independent predictor of 6-month mortality (hazard ratio=1.063, 95% CI=1.037–1.089, P<0.001). The combination of a discharge BNP ≤319pg/mL and percentage BNP reduction ≥7.71% was associated with significantly lower mortality (4.8% versus 27.2%, relative risk=0.134, 95% CI=0.046–0.387, P<0.001). ConclusionThe absolute BNP value at discharge is a more accurate predictor of 6-month mortality than the magnitude of percentage in-hospital BNP reduction and baseline BNP.

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.

FLAIR Hyperintense Vessel Sign of Both MCAs with Severe Heart Failure.

Introduction. Fluid-attenuated inversion recovery hyperintense vessels (FHVs) can be seen in patients with occlusion or severe stenosis of the cerebral arteries. FHVs are known to reflect stagnant or slow blood flow within the cerebral artery. Case Report. A 75-year-old woman presented with suddenly developed gait disturbance. She had a history of hypertension, heart failure, and dementia. Brain MRI demonstrated FHVs within both middle cerebral arteries (MCAs). However, there was no acute ischemic lesion and severe stenosis or occlusion of the cerebral arteries. In the baseline routine laboratory investigations, the AST, ALT, and B-type natriuretic peptide levels were elevated. Transthoracic echocardiography (TTE) showed mitral valve prolapse with severe regurgitation. Blood pressure control and conservative management for ischemic hepatitis were performed. After 7 days, the transaminase levels were normalized, and the patient was able to walk with normal gait. Conclusions. In this patient, underlying chronic cerebral hypoperfusion and additionally decreased systemic perfusion seemed to provoke ischemic hepatitis and contribute to the development of FHVs.