proBNP Concentrations Research Articles

Head-to-head comparison of the prohormone proBNP1–108 with BNP and Nt-proBNP in patients admitted to emergency department

B-type natriuretic peptide (BNP) and amino-terminal proBNP (Nt-proBNP) are derived from a common precursor, the proBNP(1-108) (proBNP), synthesized by cardiomyocytes. We determined proBNP concentrations in patients admitted to ED and suspected of CHF. One hundred fifty six consecutive patients admitted to ED were included. ProBNP, BNP and Nt-proBNP levels were determined at admission. In this ED population, assays for proBNP, BNP and Nt-proBNP were positively and significantly correlated. Circulating levels of proBNP were higher in patients admitted to ED for CHF than in patients admitted to ED other reasons. Applying receiver operating characteristic curve (ROC) analysis for the diagnosis of CHF, the area under the curve (AUC) was 0.92 for proBNP. Our study demonstrated that proBNP testing, the precursor of BNP and Nt-proBNP, appears as a relevant tool to assist the diagnosis of CHF in patients admitted to ED.

Predicting mortality and hospital admission in patients with COPD

To quantify the ability of N-terminal pro-brain natriuretic peptide (NT pro-BNP) to predict mortality and hospitalization in patients with chronic obstructive airways disease (COPD). Prospective single-centre observational study of 140 consecutive patients aged at least 18 years with COPD between 27 March 2004 and 28 February 2008 (median follow-up 3.9 years). Sixty-five (46%) men, 26 (19%) O2 therapy, 115 (82%) smokers, 38 (27%) patients receiving diuretics, 15 (11%) left-ventricular ejection fraction less than 45%. Median [interquartile range (IQR)] NT pro-BNP concentration 16.2 (25.4) pmol/l. NT pro-BNP was higher in those with a dilated left atrium (P<0.001), aortic stenosis (P=0.02), left-ventricular systolic dysfunction (P=0.027), right ventricular impairment (P=0.011), atrial fibrillation (P<0.001), patients receiving diuretics (P=0.010) and angiotensin-converting enzyme (ACE) inhibitors (P=0.006). One-year mortality and hospitalization rates were 2.9 and 25.4%. The median (IQR) time to hospitalization and length of first hospital stay: 383.5 (605) and 4.0 (7.0) days. NT pro-BNP was an excellent discriminator of right-ventricular impairment (C statistic=0.90) and predicted survival (highest quartile versus lowest quartile relative risk=3.02, P=0.001), but not hospital admission. After adjustment this association was not significant. NT pro-BNP predicts survival, but not hospital admission in patients with COPD. The ability of NT pro-BNP to independently predict death or hospitalization is superseded by the presence of a dilated left atrium, aortic stenosis and left-ventricular systolic dysfunction.

Reference Limits for N-Terminal-pro-B-Type Natriuretic Peptide in Healthy Individuals (from the Framingham Heart Study)

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a commonly measured cardiovascular biomarker in ambulatory and hospital settings. Nonetheless, there are limited data regarding "normal" ranges for NT-pro-BNP in healthy subjects, despite the importance of such information for interpreting natriuretic peptide measurements. In this study, a healthy reference sample free of cardiovascular disease from the Framingham Heart Study Generation 3 cohort was examined; there were 2,285 subjects (mean age 38 years, 56% women). Plasma NT-pro-BNP levels were measured using the Roche Diagnostics Elecsys 2010 assay, and reference values (2.5th, 50th, and 97.5th quantiles) were determined using empiric and quantile regression methods. Gender, age, blood pressure, and body mass index accounted for approximately 33% of the interindividual variability in NT-pro-BNP in the reference sample. NT-pro-BNP values were substantially higher in women compared to men at every age, and levels increased with increasing age for both genders. Using quantile regression, the upper reference values (97.5th quantile) for NT-pro-BNP were 42.5 to 106.4 pg/ml in men (depending on age) and 111.0 to 215.9 pg/ml in women. Intraindividual variability was assessed in an additional 12 healthy subjects, who had serial NT-pro-BNP measurements over 1 month. Intraclass correlation was 0.85, indicating that most of the variability in NT-pro-BNP concentrations was among rather than within subjects. However, the reference change value was 100%, suggesting that small proportional differences in NT-pro-BNP could be attributable to analytic variability. In conclusion, the reference limits obtained from this large, healthy, community-based sample may aid in the evaluation of NT-pro-BNP concentrations measured for clinical and research purposes.

Human Pro–B-Type Natriuretic Peptide Is Processed in the Circulation in a Rat Model

The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides. We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP. ProBNP was effectively processed in the circulation into BNP (1-32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively. In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.

Prognostic significance and correlations of neurohumoral factors in early and late postoperative period after Fontan procedure

We focused on neurohumoral activity and its clinical correlates early and late after fenestrated, lateral intra-atrial total cavopulmonary connection (TCPC). Between 2007 and 2010, we prospectively studied 28 early and 48 late postoperative TCPC patients. Plasma concentrations of vasopressin, endothelin-1, proBNP, proANP were determined. We reviewed clinical data to determine relationship between neurohumoral activation and clinical status after TCPC. There was a significant influence of preoperative ventricular end-diastolic pressure (VEDP) (P=0.008) and vasopressin concentration (P=0.02) on the appearance of prolonged pleural effusions. A significant correlation between a combined predictor (a product of preoperative vasopressin concentration and VEDP) and time of effusions (r=0.59, P=0.006) was found. The mean respiratory equivalent of carbon dioxide at peak exercise (VE/VCO(2peak)) was significantly lower in patients operated before the second year of life compared to patients operated after two years of age (27.5±1.39 vs. 48.6±3.86; P=0.039). There was a significant correlation of endothelin-1 (r=0.84; P=0.008) and proBNP (r=0.88; P=0.02) concentrations with VE/VCO(2peak). The prolonged postoperative pleural effusions can be predicted based on the product of preoperative vasopressin concentration and VEDP. Exercise performance is related to the age at TCPC. Endothelin-1 and proBNP can be useful for identification of high-risk Fontan patients.

105 Clinical and echocardiographic determinants of n-terminal pro b-type natriuretic peptide level in patients with stable chronic obstructive airways disease: a prospective observational study of 140 patients

<h3>Background</h3> Brain natriuretic peptides have been shown to be reliable indicators of left ventricular failure and markers of risk in cardiac disease. However, patients with chronic obstructive pulmonary disease (COPD) are also known to have elevated concentrations of brain natriuretic peptides in the absence of overt cardiac disease, likely due to right ventricular strain. This has been shown to have prognostic value and has a potential role in the management of the condition; for example, it has been suggested that it could be used to guide the initiation of non-invasive ventilation. The aim of this study was to identify clinical and echocardiographic determinants of the polypeptide N-terminal pro-Brain Natriuretic Peptide (NT pro-BNP) in patients with stable COPD. <h3>Method</h3> Arterial blood gases, plasma NT pro-BNP and transthoracic echocardiographic parameters were studied in 140 patients with stable COPD attending a respiratory outpatient clinic. <h3>Results</h3> Of the 140 patients, 65 (46%) were male, 26 (19%) received home oxygen therapy, 115 (82%) were current smokers, 38 (27%) were prescribed diuretics and 15 (11%) had a left ventricular ejection fraction &lt;45%. Patients with cor pulmonale (n=6) were more likely to have left ventricular systolic dysfunction (p&lt;0.001), reduced tricuspid annular plane systolic excursion (p=0.017) and higher pulmonary artery systolic pressures (p=0.01). The median (IQR) NT pro-BNP concentration was 16.2 (25.4) pmol/l. Concentrations were significantly higher in those with a dilated left atrium, aortic stenosis, left ventricular systolic dysfunction, right ventricular impairment, atrial fibrillation and those prescribed diuretics and ACE inhibitors. Significant predictors of NT pro-BNP were a dilated left atrium, aortic stenosis and left ventricular systolic dysfunction. NT Pro-BNP was an excellent discriminator of RV impairment (C statistic=0.90). <h3>Conclusions</h3> NT pro-BNP readily identifies patients with stable COPD who have right ventricular dysfunction. However, several other clinical variables also associated with increased NT pro-BNP concentrations are prevalent in this population. This is likely to confound clinical decision making.

B-type Natriuretic Peptide Secretion following Scuba Diving

To examine the neurohormonal effects of a scuba dive, focusing on the acute changes in the plasma concentrations of the different peptide fragments from the B-type natriuretic peptide (BNP) precursor. We studied 12 healthy scuba divers (mean age ± standard deviation: 44 ± 7 years; range: 34-55 years; BMI: 24.8 ± 2.8 kg/m(2)), who performed a 15-m depth dive in salt water, with a bottom time of 30 min. Blood samples for BNPs (pro-B-type natriuretic peptide [pro-BNP], BNP and aminoterminal pro-BNP) and catecholamines were measured in plasma before immersion, and after the dive. A continuous electrocardiographic recording was obtained during the entire protocol. BNP, aminoterminal pro-BNP and pro-BNP plasma concentrations slightly, but significantly, increased after the scuba dive (18 ± 15 to 21 ± 11 ng/l, p = 0.020; 32 ± 19 to 38 ± 21 ng/l, p = 0.008; and 7.8 ± 1.6 to 10.3 ± 3.6 ng/l, p = 0.028, respectively) in parallel with norepinephrine concentration (743 ± 323 to 1163 ± 656 ng/l, p = 0.014), with no variations in total plasma proteins, hematocrit or osmolality. A persistent sinus tachycardia was observed during all phases of the dive. A 15-m depth scuba dive induces an acute slight release of the different peptide fragments from the BNP precursor, likely through the stimulation of a constitutive secretory pathway promoted by adrenergic activation and cardiac chamber dilation.

Prognostic Value of Tissue Doppler Echocardiographic Imaging in Elderly Patients with Acute Myocardial Infarction

The ratio of mitral end-diastolic velocity and mitral annular early diastolic motion velocity (E/e') has predictive value in patients with acute coronary syndromes (ACS). Both E and e' velocities change with age. The prognostic value of E/e' in elderly patients with ACS has not been established yet. The aim of the study was to assess the prognostic significance of E/e' in patients over 65 with ACS. The study involved 168 patients, mean age 79 years. Echocardiography was performed within first 24 hours of ACS. Clinical evaluation, 6-minute walk test, echocardiography and plasma level of NT pro-BNP were performed 12 months later. Patients, who were still alive after 1-year follow-up had significantly lower E/e' during hospitalization: 11.1 ± 3 versus 15.1 ± 5 (P < 0.05). The optimal cutoff value of E/e' differentiating survivors and nonsurvivors after 12 month follow-up was 12. Initial E/e' was an independent predictor of mortality during 1-year follow-up. E/e' ratio during hospitalization significantly correlated with NT pro-BNP concentration (r = 0.48, P < 0.001) and 6-minute walking distance: (r =-0.32, P < 0.05) after 1-year follow-up. (1) In patients over 65 with myocardial infarction, E/e' above 12 is an independent predictor of death during 1-year follow-up. (2) E/e' ratio in acute phase of myocardial infarction correlated significantly with N pro-BNP level and 6-minute walking distance after 1-year follow-up.

Therapeutic Changes of Plasma N-Terminal Pro-Brain Natriuretic Peptide Concentrations in 9 Dogs with Patent Ductus Arteriosus

The plasma N-terminal proBNP (NT-proBNP) concentration is measured for determining the diagnosis and severity of heart failure in dogs. However, it is still unclear whether measurements of circulating NT-proBNP levels provide clinical utility as an indicator of therapeutic efficacy. Thus, we investigated the surgical correction-related changes of plasma NT-proBNP concentrations in 9 dogs with patent ductus arteriosus (PDA). Physical examination, thoracic radiography and echocardiography were conducted both before and after surgery. Similarly, the plasma NT-proBNP concentrations were determined using an enzyme immunoassay for canine pro-BNP. The International Small Animal Cardiac Health Council (ISACHC) class and murmur grade were significantly improved after surgery compared with before surgery. Vertebral heart size (VHS) and cardiothoracic ratio (CTR) were significantly decreased after surgery. Fractional shortening was significantly decreased and relative wall thickness (RWT) was significantly increased after surgery. Furthermore, the plasma NT-proBNP concentrations were significantly decreased by surgical correction. The plasma NT-proBNP concentration showed significant positive correlation with the ISACHC class, murmur grade, VHS and CTR and significant negative correlation with the RWT. Therefore, measurement of plasma NT-proBNP levels can be used to monitor the effectiveness of therapies such as surgical correction of PDA.

Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure

Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. All-cause mortality and cardiovascular mortality. After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P = .01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; P < .001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P = .048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; P < .001). Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

Renal Function and Neurohormonal Changes Following Intravenous Infusions of Nitroglycerin Versus Nesiritide in Patients With Acute Decompensated Heart Failure

Background Rises in serum creatinine and efficacy have been reported as dose-related effects of nesiritide and nitroglycerin in acute decompensated heart failure (ADHF). However, no study has evaluated the comparative safety, efficacy, and biomarkers of optimally dosed nesiritide versus nitroglycerin in ADHF. Methods and Results Eighty-nine ADHF patients were prospectively randomized to receive either nesiritide (0.01 μg kg −1 min −1 ± bolus) or nitroglycerin (maximally tolerated doses by standard protocol). Blood urea nitrogen (BUN), and creatinine were obtained during 48 hours of intravenous infusion. B-Type natriuretic peptide (BNP) and N-terminal (NT) proBNP concentrations were measured during hospitalization. There were no significant differences in BUN, serum creatinine, creatinine clearance, or hospitalization and mortality. Although concentrations of BNP and NT-proBNP were significantly decreased over time, the comparative reductions between the 2 vasodilators were similar. Conclusions Nesiritide and nitroglycerin produce similar hemodynamic effects, do not worsen markers of renal function, and produce significant, yet similar, reductions in neurohormones over time. Both nitroglycerin at maximally titrated doses and nesiritide at standard doses are safe and effective in patients with ADHF who require vasodilator therapy.

Diagnostic Equivalence of an N-terminal Pro-Brain Natriuretic Peptide Point-of-Care Test to the Laboratory Method in Patients With Heart Failure and in Reference Populations

Context: Point-of-care assays allow to have analytical results available at the site of patient care delivery such as the emergency department or the intensive care unit. Objective: To demonstrate equivalence in the N-terminal (NT) pro-brain natriuretic peptide (proBNP) concentrations as measured by the point-of-care assay (POC NT-proBNP) in comparison to the laboratory assay (lab NT-proBNP) in patients with heart failure and in a reference population. Design: Multicenter study at 7 sites. The following were eligible for data analysis: 217 patients with heart failure and 189 individuals from a reference population (patients with hypertension, diabetes, chronic obstructive pulmonary disease or asthma, or apparently healthy individuals). For all study participants, NT-proBNP values both with the POC and with the laboratory assay, echocardiographic and spirometry data, and the New York Heart Association classification were available. Results: In method comparisons between POC NT-proBNP and lab NT-proBNP, the slope of the regression line was 0.99 and the correlation coefficient was 0.97. Testing on diagnostic equivalence, POC NT-proBNP versus lab NT-proBNP yielded a mean logarithmic methodical difference of −4.9% in patients with heart failure and +3.5% with the reference population. Using an age-independent cutoff of 125 ng/L, the diagnostic sensitivity of POC NT-proBNP and of lab NT-proBNP was found to be 89%, and the areas under the receiver operating characteristic curves were 0.88 or 0.89, respectively. Conclusions Our multicenter study has demonstrated the diagnostic equivalence of POC NT-proBNP with lab NT-proBNP both in the diagnosis of heart failure and in the differential diagnosis of a reference population. Consequently, clinical experiences and indications with the laboratory assay could be applied to the POC assay as well.

Impact of Increased Body Mass Index on Accuracy of B-Type Natriuretic Peptide (BNP) and N-Terminal proBNP for Diagnosis of Decompensated Heart Failure and Prediction of All-Cause Mortality

BNP and N-terminal proBNP (NT-proBNP) concentrations may be depressed in patients with increased body mass index (BMI). Whether increased BMI affects accuracy of these biomarkers for diagnosing decompensated heart failure (HF) and predicting outcomes is unknown. We measured BNP and NT-proBNP in 685 patients with possible decompensated HF in a free-living community population subdivided by BMI as obese, overweight, and normal weight. HF diagnosis was adjudicated by a cardiologist blinded to BNP and NT-proBNP results. We tabulated all-cause mortality over a median follow-up of 401 days and assessed marker accuracy for HF diagnosis and mortality by ROC analysis. Of the 685 patients, 40.9% were obese (n = 280), 28.2% were overweight (n = 193), and 30.9% had normal BMI (n = 212). Obese patients had lower BNP and NT-proBNP compared with overweight or normal-weight individuals (P < 0.001) and decreased mortality compared with normal-weight individuals (P < 0.001). Both biomarkers added significantly to a multivariate logistic regression model for diagnosis of decompensated HF across BMI categories. NT-proBNP outperformed BNP for predicting all-cause mortality in normal-weight individuals (chi(2) for BNP = 6.4, P = 0.09; chi(2) for NT-proBNP = 16.5, P < 0.001). Multivariate regression showed that both biomarkers remained significant predictors of decompensated HF diagnosis in each BMI subgroup. In this study population, obese patients had significantly lower BNP and NT-proBNP that reflected lower mortality. BNP and NT-proBNP can be used in all BMI groups for decompensated HF diagnosis, although BMI-specific cutpoints may be necessary to optimize sensitivity.

N-terminal fragment of proBNP is a marker of risk for right ventricular dysfunction and cardiac complications in thalassemia major

Introduction Cardiac complications are the main cause of morbidity and mortality in thalassemia major (TM). In particular, thalassemic cardiomyopathy include forms with right involvement difficult to detect by usual approach, whereas early diagnosis could permit early treatment and improvement in prognosis. Plasma N-terminal fragment of proBNP (NT-proBNP) concentration holds a known value in asymptomatic cardiac patients, too, but its usefulness in the management of TM has not been fully investigated.

Prognostic efficacy of cardiac biomarkers for mortality in dialysis patients

The high prevalence of cardiovascular mortality in the end-stage renal disease population is well established. The aim of this current study was to document the relative prognostic significance of established cardiac biomarkers troponin T (TnT), troponin I (TnI), B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) in this population. A prospective cohort study of dialysis patients undertaken in a single tertiary centre in Australia. Relevant clinical and biochemical information was collected at entry and all patients followed up prospectively without any loss to follow up. End-point of interest was all-cause mortality. Statistical analysis using Cox proportional hazards was used to study relationship between competing covariates and outcome. A total of 143 patients with a mean age of 59.67 +/- 15.49 years was followed up for a median duration of 30 months. Of these patients, 89.3% were white Australians of European ancestry. Twenty-seven per cent had an established diagnosis of diabetes mellitus. The mean concentrations (+/-SD) of TnT, TnI, BNP and N-terminal peptide pro-BNP (NT-pro-BNP) were 0.08 +/- 0.04 microg/L, 0.09 +/- 0.2 microg/L, 270 +/- 117 ng/L and 1434 +/- 591 ng/L respectively. Twenty-eight subjects died during the period of follow up. By univariate analysis, all cardiac markers (TnT, TnI, BNP, NT-pro-BNP and C-reactive protein) were significantly associated with an increase in mortality. On Cox proportionate hazards analysis, only albumin and NT-pro-BNP showed a significant association with mortality, with hazard ratios of 0.834, 95% confidence interval (CI) 0.779-0.893, P < 0.001, and 1.585, 95%CI 1.160-20165, P = 0.004 respectively. In patients with end-stage renal failure on dialysis NT-pro-BNP provides greater prognostic information compared with TnT and TnI.

Effect of Balloon Valvuloplasty in Patients With Severe Aortic Stenosis on Levels of N-Terminal Pro-B-Type Natriuretic Peptide

Plasma levels of brain natriuretic peptide (BNP) have been shown to correlate to aortic stenosis severity and are predictive of symptom development and survival. They also predict postoperative outcomes after valve replacement in patients with aortic stenosis. The early evolution of N-terminal-pro-BNP (NT-pro-BNP) levels after 50 aortic balloon valvuloplasty procedures performed in 45 patients was investigated. The mean NT-pro-BNP concentration decreased from 7,048 +/- 7,636 pg/ml at baseline to 5,309 +/- 6,150 pg/ml at 1 to 3 days after the procedure (mean difference 1,739 pg/ml, 95% confidence interval 804 to 2,675, p = 0.001). The absolute reduction in NT-pro-BNP levels correlated to the reductions in the maximum and mean transvalvular pressure gradients (on echocardiography: c = 0.57, p = 0.004, and c = 0.54, p = 0.012, respectively; invasively: c = 0.54, p = 0.025, and c = 0.39, p = 0.019). In conclusion, NT-pro-BNP levels decrease early after aortic balloon valvuloplasty in patients with severe aortic stenosis at high surgical risk.

Acute cardiac volume load-related changes in plasma atrial natriuretic peptide and N-terminal pro-B-type natriuretic peptide concentrations in healthy dogs

Plasma atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have been used for the diagnosis of heart disease. The aim of the study was to investigate differences in secretory responses of plasma ANP and N-terminal proBNP (NT-proBNP) concentrations related to acute changes in preload. Six dogs were anaesthetised and infused intravenously with Ringer's solution (90-100mL/kg/h) for 60 min. Thereafter, furosemide was administered and dogs were monitored for 60 min. Plasma ANP and NT-proBNP concentrations were determined by chemiluminescence enzyme immunoassay and enzyme immunoassay, respectively. Volume overload significantly increased plasma ANP and NT-proBNP concentrations (P<0.001); however, preload reduction significantly reduced plasma ANP concentrations (P<0.05) without concurrent changes in plasma NT-proBNP. Mean pulmonary capillary wedge pressures were strongly correlated with plasma ANP concentrations (r=0.53, P<0.001), but not plasma NT-proBNP. Thus, plasma ANP is a useful, non-invasive parameter for measuring rapid haemodynamic changes.

Troponin T and Pro–B-Type Natriuretic Peptide in Fetuses of Type 1 Diabetic Mothers

OBJECTIVECardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function.RESEARCH DESIGN AND METHODSThis was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro–B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester.RESULTSFetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05).CONCLUSIONSBiochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

Effect of estimated glomerular filtration rate on plasma concentrations of B-type natriuretic peptides measured with multiple immunoassays in elderly individuals

Objetive:This study was designed to quantify the crude and adjusted effects of estimated glomerular filtration rate (eGFR) on N-terminal-pro-brain-natriuretic peptide (proBNP) measured with three immunoassays and brain natriuretic peptide (BNP)...

Role for precursor Pro-B type natriuretic peptide in assessing response to therapy and prognosis in patients with decompensated heart failure treated with nesiritide

Background ProBNP, the precursor peptide to BNP and NT-proBNP (NP), circulates in patients with chronic heart failure (HF) and appears to be the predominant form of NP. This heterogeneity may confound interpretation of NP concentrations. The aim of this study was to evaluate the response to therapy and prognostic influence of proBNP in a cohort of patients admitted to hospital for decompensated HF. Methods We prospectively evaluated 40 Class III–IV patients who received clinically-indicated nesiritide infusions as part of their care. Blood was drawn before, during, and post-infusion, and assayed for proBNP, BNP, and NT-proBNP. Results All biomarkers were increased at baseline consistent with HF. ProBNP and NT-proBNP demonstrated significant reductions in response to therapy (42% and 18% post-infusion, respectively). In the patients who experienced post-hospital mortality (40% at 6 months), baseline proBNP and BNP concentrations were significantly lower than in survivors. This paradoxical finding may be explained by the end-stage nature of this patient cohort possibly experiencing exhaustion of their NP systems. Conclusions Circulating concentrations of proBNP are increased in decompensated HF and similar to NT-proBNP are reduced in response to acute therapy. Paradoxically and similar to BNP, baseline proBNP concentrations were lower in post-hospital non-survivors. While hypothesis generating, the results of this study support a role for proBNP in monitoring therapy and predicting short-term outcome. These findings need to be confirmed in a patient cohort without nesiritide therapy and more moderate HF.