Median B-type Natriuretic Peptide Level Research Articles

Impact of the degree of worsening renal function and B-type natriuretic peptide on the prognosis of patients with acute heart failure.

The impact of the degree of worsening renal function (WRF) and B-type natriuretic peptide (BNP) on the prognosis of patients with acute heart failure (AHF) is still debatable. The present study investigated the influence of different degrees of WRF and BNP levels at discharge on 1-year all-cause mortality in AHF. Hospitalized AHF patients diagnosed with acute new-onset/worsening of chronic heart failure (HF) between January 2015 and December 2019 were included in this study. Patients were assigned into high and low BNP groups based on the median BNP level at discharge (464 pg/ml). According to serum creatinine (Scr) levels, WRF was divided into non-severe WRF (nsWRF) (Scr increased ≥0.3 mg/dl and <0.5 mg/dl) and severe WRF (sWRF) (Scr increased ≥0.5 mg/dl); non-WRF (nWRF) was defined as Scr increased of <0.3 mg/dl). Multivariable cox regression was used to evaluate the association of low BNP value and different degrees of WRF with a all-cause death, as well as testing for an interaction between the two. Among 440 patients in the high BNP group, there was a significant difference in WRF on mortality (nWRF vs. nsWRF vs. sWRF: 22% vs. 23.8% vs. 58.8%, P < 0.001). Yet, mortality did not significantly differ across the WRF subgroups in the low BNP group (nWRF vs. nsWRF vs. sWRF: 9.1% vs. 6.1% vs. 15.2%, P = 0.489). In multivariate Cox regression analysis, low BNP group at discharge (HR, 0.265; 95%CI, 0.162-0.434; P < 0.001) and sWRF (HR, 2.838; 95%CI, 1.756-4.589; P < 0.001) were independent predictors of 1-year mortality in AHF.There was a significant interaction between low BNP group and sWRF(HR, 0.225; 95%CI, 0.055-0.918; P < 0.05). nsWRF does not increase the 1-year mortality in AHF patients, whereas sWRF does. A low BNP value at discharge is associated with better long-term outcomes and mitigates the adverse effects of sWRF on prognosis.

Correlation Between Plasma B-Type Natriuretic Peptide Levels and Remote Dielectric Sensing in Patients with Heart Failure.

Plasma B-type natriuretic peptide (BNP) is a practical tool with which to estimate hemodynamic status including intra-cardiac pressure in patients with heart failure (HF). However, plasma BNP levels cannot be measured immediately in an outpatient private clinic. We investigated the value of remote dielectric sensing (ReDS), a novel non-invasive electromagnetic energy-based tool to quantify lung fluid amount immediately, to predict plasma BNP levels.Successive measurements of ReDS values and plasma BNP levels were performed in patients hospitalized to treat HF in a prospective manner. Correlations between ReDS values and plasma BNP levels were assessed.A total of 117 datasets for HF patients were obtained in this prospective study. The median ReDS value was 28% (interquartile range: 25%, 34%) and the median plasma BNP level was 205 (86, 469) pg/mL, both of which had a slight correlation (r = 0.234, P = 0.011). Their correlation improved when those with a body mass index less than 18.5 (n = 23) were excluded (r = 0.278, P = 0.007).ReDS might be a practical tool for estimating plasma BNP levels, particularly in outpatient private clinics where the immediate measurement of plasma BNP levels is not available.

Prognostic relevance of B-type natriuretic peptide in patients with moderate mixed aortic valve disease.

AimsData on B‐type natriuretic peptide (BNP) levels and adverse outcomes in patients with moderate mixed aortic valve disease (MAVD), defined as moderate aortic stenosis (AS) and regurgitation (AR), are scarce. Therefore, this study investigated the impact of BNP on the clinical outcomes in such patients.Methods and resultsClinical data from 81 patients (mean age, 74.1 ± 6.8 years; 50.6%, men) treated for moderate MAVD and left ventricular ejection fraction (LVEF) ≥ 50% during 2010–2018 were retrospectively analysed. Specific echocardiographic data of the study patients were LVEF of 57.8 ± 5.0%, aortic valve index of 0.64 ± 0.04 cm2/m2, peak aortic valve velocity of 3.38 ± 0.29 m/s, and AR vena contracta width of 4.2 ± 0.7 mm. The median BNP level was 61.4 pg/mL (interquartile range, 29.7–109.9). The primary endpoint was a composite of all‐cause death, heart failure hospitalization, and aortic valve replacement, and its cumulative incidence at 5 years was 57.7%. Multivariable analysis revealed that age (hazard ratio, 1.079; 95% confidence interval, 1.028–1.133; P = 0.002) and BNP levels (hazard ratio, 1.028; 95% confidence interval, 1.003–1.053; P = 0.027) were significantly related to the endpoint; specifically, BNP > 61.4 pg/mL had significantly higher incidence rates of the endpoint than those with a BNP ≤ 61.4 pg/mL (70.3% vs. 45.5% at 5 years; P = 0.018). Compared with patients with BNP ≤ 61.4 pg/mL, those with BNP > 61.4 pg/mL had significantly worse left ventricular global longitudinal strain (−17.1 ± 3.6% vs. −18.7 ± 2.6%; P = 0.029), along with higher left ventricular mass index (116.9 ± 27.8 g/m2 vs. 103.5 ± 19.7 g/m2; P = 0.014), relative wall thickness (0.45 ± 0.07 vs. 0.42 ± 0.05; P = 0.022), left atrial volume index (46.0 ± 28.4 mL/m2 vs. 31.4 ± 10.3 mL/m2; P = 0.003), pulmonary artery systolic pressure (32.6 ± 9.7 mmHg vs. 28.2 ± 4.7 mmHg; P = 0.011), and prevalence of moderate or greater tricuspid regurgitation (15.0% vs. 0.0%; P = 0.012).ConclusionsPatients with moderate MAVD are at higher risk of unfavourable clinical outcomes, and age and BNP are independently related to the occurrence of adverse events. High BNP levels may reflect extravalvular cardiac damage in patients with moderate MAVD.

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.

Left atrial volume index predicts future improvement of B-type natriuretic peptide levels after transcatheter aortic valve replacement.

In patients with symptomatic severe aortic stenosis (AS), those who experienced readmission due to heart failure after transcatheter aortic valve replacement (TAVR) showed poor prognosis. Furthermore, poor B-type natriuretic peptide (BNP) improvement is associated with increased morbidity and mortality. However, little is known about the clinical parameters related to the change in BNP levels after TAVR procedure. This study population consisted of 127 consecutive patients of symptomatic severe AS with preserved ejection fraction (EF) who underwent transfemoral TAVR (TF-TAVR). Comprehensive transthoracic echocardiography was performed prior to the day of TF-TAVR. BNP was measured serially before and 1year after TF-TAVR. The median BNP level was significantly decreased from 252.5pg/ml to 146.8pg/ml in all 127 patients 1year after TF-TAVR (P < 0.01). However, the patients could be divided into 2 groups according to decrease (72%) or increase (28%) in plasma BNP level. Multivariate logistic regression analysis revealed that Aortic valve (AV) peak velocity, pre-procedural BNP, and larger left atrial volume index (LAVI) were found to be an independent predictor of increased BNP level 1year after TAVR (OR 0.55, 95% CI 0.38-0.77; P < 0.01). LAVI were negatively correlated with the change in BNP level before and 1year after TAVR (r = 0.47, P < 0.01). The ROC analysis demonstrated that 52.9ml/m2 was the optimal cut-off value of LAVI for decreasing BNP 1year after TAVR (area under the curve 0.69) with 64% sensitivity and 70% specificity. In addition to AV peak velocity and pre-procedural BNP, LAVI independently predicts future improvement of BNP levels 1year after TAVR. Our findings indicate an additive predictive value of assessment of LAVI before TAVR procedure for risk stratification.

Sleep-disordered breathing is independently associated with elevated natriuretic peptide levels in patients with cardiovascular diseases

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66years (55-74years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9pg/ml (23.5-146.4pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17-10.88; moderate: OR, 3.62; 95% CI 2.17-6.02; mild: OR, 2.22: 95% CI 1.42-3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD.

Gender differences in clinical characteristics in wild-type transthyretin amyloidosis cardiomyopathy

Abstract Aims A significant male predominance has been reported in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). In other words, the female ATTRwt-CM may be overlooked and gender differences in ATTRwt-CM remain unclear. This study aims to examine gender differences in clinical characteristics and diagnostic approaches in ATTRwt-CM. Methods and results We retrospectively evaluated 171 consecutive ATTRwt-CM patients diagnosed at our university hospital between December 2002 and December 2020. Twenty-two patients (12%) were women. Women were significantly older at diagnosis (77.3 years vs. 83.3 years; P&amp;lt;0.001) and had a higher advanced New York Health Association functional class (2.23±0.70 vs. 2.57±0.81; P=0.04) than men. In echocardiography, mean interventricular septum diameter was less thick (15.8 mm vs. 14.5 mm; P=0.03) and ejection fraction was preserved (51.7% vs. 57.7%; P=0.08) in women. The mean heart-to-contralateral ratio obtained using 99mTc-labeled pyrophosphate (99mTc-PYP) was significantly lower in women than in men (1.89 vs. 1.64; P=0.001). There was no significant gender difference in high-sensitivity median cardiac troponin T levels at diagnosis (0.055 ng/mL vs. 0.069 ng/mL; P=0.30) or history of carpal tunnel syndrome (57% vs. 55%; P=0.93) and electrocardiograms findings. However, the median B-type natriuretic peptide level was significantly higher (254 pg/mL vs. 434 pg/mL; P=0.02) in women. Moderate to severe aortic stenosis was more frequently observed in women (5% vs. 50%; P&amp;lt;0.001). Histological (78% vs. 59%; P=0.07) and genetic confirmation (78% vs. 59%; P=0.003) of ATTRwt-CM were not performed in women. Conclusion Women with ATTRwt-CM were predominantly octogenarians, less hypertrophic, and had weaker cardiac uptake of the 99mTc-PYP tracer than men with ATTRwt-CM. These characteristics contribute to the underdiagnosis of ATTRwt-CM in women. The diagnosis of ATTRwt-CM in women is challenging. Therefore, we must be familiar with the clinical characteristics of women with ATTRwt-CM. Funding Acknowledgement Type of funding sources: None.

Abstract 15938: B-type Natriuretic Peptide Levels Do Not Predict the Need for Mechanical Ventilation in Hospitalized Patients With COVID-19

Introduction: B-type natriuretic peptide (BNP) is widely used as a biomarker of heart failure and typically rises in response to increased intracardiac pressure. BNP levels have been measured in patients with coronavirus disease 2019 (COVID-19) to assess the cardiovascular contribution to respiratory failure and guide diuresis. Whether BNP levels do predict the need for mechanical ventilation (MV) is however unknown. Methods: The Michigan Medicine Covid-19 Cohort (M 2 C 2 ) is an ongoing prospective observational study in which detailed clinical, laboratory and outcomes data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without symptoms of COVID-19 were not included in this cohort. We identified 495 patients admitted between March 1 st and May 1 st for COVID-19, of whom 290 (58.6%) had BNP levels measured during their hospitalization. We examined the association between BNP and the need for MV during their hospitalization. Results: Among the 290 patients evaluated, the mean age was 62 (SD 15), 169 (58.3%) were male, 135 (46.6%) were blacks, and 61 (21.0%) had pre-existing heart failure. The median BNP level was 50 pg/ml, and 104 (35.9%) of patients had a BNP level &gt; 100 pg/ml. A total of 130 (44.8%) required MV during their hospitalization. The median BNP level in patients who required MV was 63 pg/ml (IQR 25-171), compared to 46 pg /ml (IQR 17-187) in patients who did not, P=0.23. In multivariable analysis adjusting for age, gender, race, pre-existing heart failure, and serum creatinine on admission, BNP&gt;100 pg/ml was not associated with the need for MV. Conclusions: In patients hospitalized for COVID-19, BNP levels were not associated with the need for MV, suggesting that the cardiovascular contribution to respiratory failure in these patients is likely minor compared to the inflammatory response or direct impact of the virus.

B-type natriuretic peptide and outcome in patients with apical hypertrophic cardiomyopathy

BackgroundAlthough elevated B-type natriuretic peptide (BNP) levels predict outcome in patients with hypertrophic cardiomyopathy (HCM), the association between BNP levels and outcome in patients with the apical phenotype of HCM remains unclear. We evaluated the impact of elevated BNP levels on outcome in a cohort of apical HCM patients. MethodsAmong 432 HCM patients, 144 with an apical phenotype were examined. Plasma BNP levels were measured at the time of the initial evaluation. ResultsThe median (interquartile range) BNP level at initial evaluation in these patients was 188.5 (72.0–334.4) pg/mL. During a median follow-up period of 9.5 years, 34 patients experienced HCM-related adverse outcomes, including 2 patients with sudden death, 5 with appropriate implantable defibrillator shocks, 3 with stroke-related death, 8 with non-fatal stroke, and 16 with heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis of the prognostic value of BNP for the combined endpoint gave an area under the ROC curve of 0.756, and optimal BNP cut-off point of 226.0pg/mL. Patients with high BNP levels (≥226.0pg/mL) were at significantly greater risk of the combined endpoint (log-rank p<0.001) than patients with low BNP levels. Multivariable analysis that included BNP levels and potential confounders showed that high BNP levels were an independent determinant of the combined endpoint (adjusted hazard ratio: 3.71; p=0.002). ConclusionsMeasuring BNP may help stratify the risk of HCM-related adverse outcome in apical HCM patients.

Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients

BackgroundIn the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients. MethodsWe retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment. ResultsMorphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p < 0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment. ConclusionsThis single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients.

Prognostic Value of BNP Reduction During Hospitalization in Patients With Acute Heart Failure

Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF. We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction. The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.

Association of B-Type Natriuretic Peptide Level With Residual Kidney Function in Incident Peritoneal Dialysis Patients.

Residual kidney function (RKF) is an important factor influencing both technique and patient survival in peritoneal dialysis (PD) patients. B-type natriuretic peptide (BNP) is considered a marker of cardio-renal syndrome. The relationship between BNP and RKF in PD patients remains unclear. We conducted a prospective study of 89 patients who had started and continued PD for 6 months or more in Kyushu University Hospital between June 2006 and September 2015. Participants were divided into low BNP (≤ 102.1 ng/L) and high BNP (> 102.1 ng/L) groups according to median plasma BNP level at PD initiation. The primary outcome was RKF loss, defined as 24-hour urine volume less than 100 mL. We estimated the association between BNP and RKF loss using a Kaplan-Meier method and Cox proportional hazards model and compared the rate of RKF decline between the 2 groups. To evaluate the consistency of the association, we performed subgroup analysis stratified by baseline characteristics. During the median follow-up of 30 months, 30 patients lost RKF. Participants in the high BNP group had a 5.87-fold increased risk for RKF loss compared with the low BNP group after adjustment for clinical and cardiac parameters. A high plasma BNP level was more clearly associated with RKF loss in younger participants compared with older participants in subgroup analysis. B-type natriuretic peptide may be a useful risk marker for RKF loss in PD patients. The clinical importance of plasma BNP level as a marker of RKF loss might be affected by age.

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.

Abstract 11015: Why Don’t Heart Failure Patients Respond to Worsening Symptoms?

Background: Long delays in seeking medical care are common in patients with worsening symptoms of heart failure (HF) and lead to longer lengths of hospital stay, increased healthcare costs, and increased morbidity and mortality. However, patient-reported reasons for delay have rarely been explored. Objective: To describe patient-reported reasons for delay in seeking medical care for worsening symptoms. Methods: As part of a clinical trial designed to reduce HF readmission and mortality for worsening symptoms, we administered the HF Symptom Response Questionnaire to all patients prior to intervention. The instrument measures reasons why patients delay seeking treatment. All patients had a recent hospitalization for HF, were community dwelling in a rural location, and had no cognitive impairments as measured with the Mini-Cog. Results: A total of 614 HF patients (59% male, NYHA class III/IV 35%, 19% without a high school education, mean age 66±13 years, median b-type natriuretic peptide level 186 pg/ml [25th percentile = 72, 75th percentile = 462] were studied. The most common reasons for not seeking early treatment were symptom uncertainty (62.4%), symptoms seem vague or came on too gradually (67.4%), symptoms slightly different from last episode (55.2%) and the symptoms didn’t seem to be serious enough (62.2%). Other reasons include embarrassment at seeking treatment (23.9%), not wanting to second guess the doctor (21.7%), financial concerns (19.9%), transportation issues (16.4%), and other (10.7%). Reasons given in the other category included afraid/don’t like doctors or hospitals, care of pets at home, family needs them, not wanting to bother others, denial/don’t want to know/fear of knowing, and weather. Conclusions: Despite experiencing worsening HF symptoms of such intensity that hospitalization is required, most patients do not perceive that symptoms are intense or certain enough to warrant action. In many, treatment seeking decisions are superseded by factors not related to symptom appraisal such as family obligations, fear or denial, and embarrassment. Education to improve response to worsening HF symptoms requires skills in symptom appraisal, and counseling to overcome personal barriers to seeking treatment.

Early Elevated B-Type Natriuretic Peptide Levels are Associated with Cardiac Dysfunction and Poor Clinical Outcome in Pediatric Septic Patients.

To determine the B-type natriuretic peptide (BNP) level in pediatric septic patients, and to investigate its association with cardiovascular dysfunction and clinical outcome. Pediatric patients with sepsis or septic shock were prospectively enrolled in our pediatric intensive care unit (PICU). On day 1 of admission, plasma BNP levels were measured at the time-point of echocardiography. Myocardial dysfunction was defined as left ventricular fractional shortening (FS) < 30%. Inotropic support was quantified by inotropic scores and disease severity was assessed by Pediatric Risk of Mortality (PRISM) III scores. Therafter, associations between BNP levels and clinical parameters were analyzed. There were 94 patients (mean: 5.6 yr, range: 2 mo-17 yr) that were consecutively enrolled in this study. The median BNP level was 127 pg/ml (range: 5 to 4950 pg/ml). BNP levels were correlated with PRISM III (rho = 0.36, p = 0.001) and C-reactive protein level (r = 0.39, p = 0.001). The median BNP levels were not only higher in patients with septic shock (n = 34) than those with sepsis (n = 58) (213 vs. 54 pg/ml, p = 0.0004), but also higher in patients with myocardial dysfunction (n = 18) than those with preserved myocardial function (n = 66) (765 vs. 65 pg/ml, p < 0.001). We also found that BNP levels correlated negatively with FS (r = -0.56, p < 0.001) and positively with inotropic scores (r = 0.34, p = 0.04). Most importantly, the median BNP levels were higher in non-survivors (n = 13) than survivors (n = 81) (367 vs. 106 pg/ml, p = 0.003). BNP levels are elevated in pediatric septic patients early in the disease course, and increased levels are associated with cardiovascular dysfunction and worse clinical outcome. B-type natriuretic peptide; Cardiac function; Pediatric; Sepsis; Septic shock.

B-Type Natriuretic Peptide Clinical Activation in Aortic Stenosis: Impact on Long-Term Survival

This study was conducted to define the association between serum B-type natriuretic peptide (BNP) activation andsurvival after the diagnosis of aortic stenosis (AS). In AS, the link between BNP levels and clinical outcome is in dispute. Failure to account for the normal shifting ofBNP ranges with aging in men and women, not using hard endpoints (survival), and not enrolling large series ofpatients have contributed to the uncertainty. A program of prospective measurement of BNP levels with Doppler echocardiographic AS assessment during the same episode of care was conducted. BNP ratio (measured BNP/maximal normal BNP value specific to age and sex) >1 defined BNP clinical activation. In 1,953 consecutive patients with at least moderate AS (aortic valve area 1.03 ± 0.26 cm(2); mean gradient 36±19 mm Hg), median BNP level was 252 pg/ml (interquartile range: 98 to 592 pg/ml); BNP ratio 2.46 (interquartile range 1.03 to 5.66); ejection fraction (EF) 57% ± 15%, and symptoms present in 60% of patients. After adjustment for all survival determinants, BNP clinical activation (BNP ratio >1) independently predicted mortality after diagnosis (p< 0.0001; hazard ratio [HR]: 1.91; 95% CI: 1.55 to 2.35) and provided incremental power to the survival predictive model (p<0.0001). Eight-year survival was 62 ± 3% with normal BNP levels, 44± 3% with BNP ratio of 1 to 2 (adjusted HR: 1.49; 95% CI: 1.17 to 1.90), 25 ± 4% with BNP ratio of 2 to 3 (adjusted HR: 2.12; 95% CI: 1.63 to2.75), and 15 ± 2% with BNP ratio of≥3 (adjusted HR: 2.43; 95% CI: 1.94 to 3.05). This strong link to survivalwas confirmed in asymptomatic patients with normal EF (adjusted HR: 2.35 [95% CI: 1.57 to 3.56] for BNPclinical activation and 2.10 [95% CI: 1.32 to 3.36] for BNP ratio of 1 to 2, 2.25 [95% CI: 1.31 to 3.87] for BNP ratio of 2 to 3, 3.93 [95% CI: 2.40 to 6.43] for BNP ratio of≥3). Aortic valve replacement was associated with survival improved by a similarly high margin (p= 0.54) with BNP ratio of<2 (HR: 0.68; 95% CI: 0.52 to 0.89; p= 0.003) or BNP ratio of>2(HR: 0.56; 95% CI: 0.47 to 0.66; p< 0.0001). In this large series of patients with AS, BNP clinical activation was associated with excess long-term mortality incrementally and independently of all baseline characteristics. Higher mortality with higher BNP clinical activation, even in asymptomatic patients, emphasizes the importance of appropriate clinical interpretation of BNP levels in managing patients with AS.

Factors Associated with Serum B-Type Natriuretic Peptide in Infants with Single Ventricles

Data regarding the value of B-type natriuretic peptide (BNP) measurements in infants with a single-ventricle (SV) physiology are lacking. This analysis aimed to describe the BNP level changes in infants with an SV physiology before and after superior cavopulmonary connection (SCPC) surgery. Levels of BNP were measured by a core laboratory before SCPC (at 5.0 ± 1.6 months) and at the age of 14 months during a multicenter trial of angiotensin-converting enzyme inhibition therapy for infants with SV. Multivariable longitudinal analysis was used to model the associations between BNP levels and three sets of grouped variables (echocardiography, catheterization, growth). Multivariable analysis was performed to assess associations with patient characteristics at both visits. Associations between BNP levels and neurodevelopmental variables were investigated at the 14 month visit because neurodevelopmental assessment was performed only at this visit. The BNP level was significantly higher before SCPC (n = 173) than at the age of 14 months (n = 134). The respective median levels were 80.8 pg/ml (interquartile range [IQR], 35-187 pg/ml) and 34.5 pg/ml (IQR, 17-67 pg/ml) (p < 0.01). A BNP level higher than 100 pg/ml was present in 72 subjects (42 %) before SCPC and in 21 subjects (16 %) at the age of 14 months. In the 117 patients who had BNP measurements at both visits, the median BNP level decreased 32 pg/ml (IQR, 1-79 pg/ml) (p < 0.01). In the longitudinal multivariable analysis, higher BNP levels were associated with a higher end-systolic volume z-score (p = 0.01), a greater degree of atrioventricular (AV) valve regurgitation (p < 0.01), a lower weight z-score (p < 0.01), and a lower length z-score (p = 0.02). In multivariable analyses, a higher BNP level at the age of 14 months was associated with arrhythmia after SCPC surgery (p < 0.01), a prior Norwood procedure (p < 0.01), a longer hospital stay after SCPC surgery (p = 0.04), and a lower Bayley psychomotor developmental index (p = 0.02). The levels of BNP decreases in infants with SV from the pre-SCPC visit to the age of 14 months. A higher BNP level is associated with increased ventricular dilation in systole, increased AV valve regurgitation, impaired growth, and poorer neurodevelopmental outcomes. Therefore, BNP level may be a useful seromarker for identifying infants with SV at risk for worse outcomes.

Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease

BackgroundElevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).PurposeTo examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD).MethodsIn all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects.ResultsIn the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9–129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0–45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0–53.7) for grade II; 22.1 (9.1–52.6) for grade III; and 17.2 (9.6–22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8–32.2) pg/mL before AECOPD, 72.7 (27.7–146.3) pg/mL during AECOPD, and 14.6 (12.9–39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4–555.0) than in 48 successfully discharged subjects 48.5 (24.2–104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman’s rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman’s rank correlation coefficient =−0.221, P=0.108).ConclusionA modest elevation of plasma BNP is observed during AECOPD. It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure.

Relationship between sex, ejection fraction, and B-type natriuretic peptide levels in patients hospitalized with heart failure and associations with inhospital outcomes: Findings from the Get With The Guideline–Heart Failure Registry

In heart failure (HF), there are known differences in plasma B-type natriuretic peptide (BNP) levels between reduced and preserved ejection fraction (EF), but few HF studies have explored sex differences. We sought to evaluate the relationship between sex, EF, and BNP in HF patients and determine prognostic significance of BNP as it relates to sex and EF. We included hospitals in Get With The Guidelines-Heart Failure that admitted 99,930 HF patients with reduced (EF <40%), borderline (EF 40%-49%), or preserved (EF ≥50%) EF. The primary end point was inhospital mortality. Multivariate models were used to compute odds ratios while accounting for hospital clustering. There were 47,025 patients with reduced (37% female), 13,950 with borderline (48% female), and 38,955 with preserved (65% female) EF. Women compared with men had higher admission median BNP levels with the greatest difference among reduced EF and smallest difference among preserved EF (median BNP in women vs men: EF reduced 1,259 vs 1,113 pg/mL, borderline 821 vs 732 pg/mL, and preserved 559 vs 540 pg/mL; P < .001 all comparisons). Ejection fraction and sex were independently associated with BNP. Inhospital mortality was 2.7%, and patients above the median BNP level had higher mortality than those below. After adjusting for over 20 clinical variables, the ability of BNP to predict inhospital mortality was similar among all subgroups (P for heterogeneity = .47). In a large registry, we found that despite sex/EF differences in BNP values, there was no significant difference in the ability of BNP to predict inhospital mortality among these subgroups.

Role of B-type natriuretic peptide as a marker of mortality in acute kidney injury patients treated with continuous renal replacement therapy

Objectives: Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to fluid volume overload, and is elevated in AKI patients. The purpose of the study was to assess whether BNP levels at the time of starting CRRT could be used as a predictor of mortality in patients with AKI receiving CRRT. Methods: We conducted a prospective observational cohort study enrolling 149 patients with AKI receiving CRRT. The primary outcome was mortality during CRRT. Results: The median BNP level of 84 (56.3%) patients who expired was significantly higher than that of those who survived (1812.5 vs. 475.0 pg/mL; p = 0.01). Receiver operating characteristic curves demonstrated BNP levels as a predictor of mortality during CRRT with an area under the curve of 0.77 (p = 0.000), and the optimal threshold for BNP was 1054 pg/mL. Patients with BNP levels above 1054 pg/mL had a significantly higher mortality (76.6 vs. 34.7%; p = 0.01). Conclusion: Elevated BNP level is associated with mortality in patients with AKI receiving CRRT.