B-type Natriuretic Peptide Concentrations Research Articles

B-type natriuretic peptide measurement in primary care; magnitude of associations with cardiovascular risk factors and their therapies. Observations from the STOP-HF (St. Vincent’s Screening TO Prevent Heart Failure) study

An effective prevention strategy for heart failure in primary care requires a reliable screening tool for asymptomatic ventricular dysfunction. Preliminary data indicate that B-type natriuretic peptide (BNP) may be suitable for this task. However, for the most effective use of this peptide, the interrelationships between associated risk factors and their therapies on BNP, and in particular their magnitude of effect, needs to be established in a large primary care population. Therefore, the objective of the study was to establish the extent of the association between BNP, cardiovascular risk factors and their therapies. BNP measurement and clinical review was preformed on 1122 primary care patients with cardiovascular risk factors. Multivariate analyses identified significant associates of BNP concentrations which were further explored to establish the magnitude of their association. Associates of BNP were age (1.36-fold increase in BNP/decade), female (1.28), β-blockers (1.90), myocardial infarction (1.36), arrhythmia (1.98), diastolic blood pressure; all p<0.01. A novel method was devised that plotted median BNP per sliding decade of age for the various combinations of these principal associates. The data presented underline the importance of considering several clinical and therapeutic factors when interpreting BNP concentrations. Most of these variables were associated with increased concentrations, which may in part explain the observed false-positive rates for detecting ventricular dysfunction using this peptide. Furthermore, the design of studies or protocols using BNP as an endpoint or a clinical tool should take particular account of these associations. This analysis provides the foundation for age, risk factor and therapy adjusted reference ranges for BNP in this setting.

Predictive value of B-type natriuretic peptide levels in patients with paroxysmal and persistent atrial fibrillation undergoing pulmonary vein isolation

Atrial fibrillation (AF) is the most common cardiac arrhythmia reducing the health-related quality of life. Radiofrequency catheter ablation (CA) became the therapy of choice in patients with drug-resistant AF with success rates between 30% and 86%. However, CA remains a challenging intervention with major complications in about 5% of cases. Therefore, stratification into high and low success patient groups would be helpful. The aim of this study was to investigate the predictive value of B-type natriuretic peptide (BNP) on the outcome of pulmonary vein isolation (PVI) in patients with paroxysmal (PAF) and persistent (Pers-AF) atrial fibrillation. In 73 patients (median age 53years, 77% men) undergoing PVI for drug-refractory PAF (n = 45) or Pers-AF (n = 28), the serum BNP concentration was measured before and 3months after the ablation procedure to assess any association of pre- and post-interventional BNP concentrations with therapeutic outcome. The patients had suffered from AF for a median of 40months. No patient had structural heart disease or an impaired left-ventricular ejection fraction. A total of 54 patients (74%) had stable sinus rhythm 3months after PVI. The median baseline BNP levels in both PAF and Pers-AF patients were significantly lower in patients with a 3-month successful PVI than those in which it was unsuccessful, 57.5pg/ml (20.4-87.9) versus 159.0pg/ml (124.1-177.5; p = 0.001) in PAF patients and 90.3pg/ml (41.0-155.0) versus 176pg/ml (89.6-297.4; p = 0.026) in patients with Pers-AF, respectively. A multiple logistic regression analysis identified pre-interventional BNP levels as the only independent predictor for 3-month PVI outcomes (p = 0.010). Nevertheless, in this study, the predictive value of BNP for PVI outcomes was not high enough to permit individual outcome prediction. After successful PVI, BNP levels were significantly lower in patients with PAF and Pers-AF (median changes -16.9 and -23.8pg/ml; p = 0.010 and p = 0.022, respectively), but not in patients with AF in follow-up (median change 9.0pg/ml and -29.6pg/ml; p = 1.000 and p = 0.109, respectively). Pre-ablation BNP level seems to be an independent marker for successful PVI procedures in patients with paroxysmal and persistent AF; however, the observed level of association is moderate.

B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.

Detection of Occult Paroxysmal Atrial Fibrillation in Stroke Patients Using High Resolution Electrocardiography

Background: Paroxysmal atrial fibrillation (AF) is highly prevalent in patients with ischemic stroke, but the diagnosis is often difficult. Methods: This study consisted of 61 stroke patients in sinus rhythm without a history of paroxysmal AF. All patients underwent P-wave signal-averaged electrocardiography (P-SAECG), echocardiography, 24-hour Holter monitoring, and measurement of plasma B-type natriuretic peptide (BNP) concentrations at admission. Results: An abnormal P-SAECG was found in 33 of 61 stroke patients. In the follow-up period of 11±3 months, paroxysmal AF developed in 19 patients (AF group). The remaining 42 patients were divided into non-AF group. An abnormal P-SAECG and frequent premature atrial contractions (PACs, 100 or more/24 hour) were detected more frequently in patients with AF group than non-AF group (89.5% vs 35.7%; p<0.001, 84.2% vs 26.2%; p<0.001, respectively). However, there were no significant differences in age, left atrial dimension, BNP concentrations between both groups. Cox proportional hazards analysis revealed that an abnormal P-SAECG (hazard ratio 21.3; p=0.003) and frequent PACs (hazard ratio 4.6; p=0.046) had significant correlation to the development of paroxysmal AF. Conclusions: An abnormal P-SAECG and frequent PACs may be novel predictors of paroxysmal AF in stroke patients. P-SAECG should be considered in stroke of undetermined etiology.

Relationship between the prognosis of emergency center patients and their biomarker levels on arrival

It is important to assess the severity of patients' conditions using various markers upon their arrival to emergency centers. In this study, we assessed the levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), D-dimer, Hb, T-Bil, BUN, and s-Cr for this purpose. Out of 1954 patients who were consecutively transferred to Kitasato University Hospital Emergency Center from June 2007 to June 2008, 1253 patients without cardiopulmonary arrest on arrival were assessed with regard to the relationship between their outcome and blood BNP, cTnI, D-dimer, Hb, T-Bil, BUN, and s-Cr levels on arrival. We divided the patients into two groups according to whether they died in hospital and whether the causes of their disease were intrinsic or extrinsic, and then made comparisons between groups. The blood concentrations of BNP, cTnI, D-dimer, T-Bil, BUN, and s-Cr were significantly high while that of Hb was significantly low in the hospital death group. In multivariate analysis, age, BNP, D-dimer, and T-Bil in the intrinsic group were found to be independent predictors of hospital death; whereas, D-dimer and T-Bil were found to be independent predictors of hospital death in the extrinsic group. In particular, the cardiogenic cases in the intrinsic cause group revealed a sensitivity of 93.3%, a specificity of 83.9%, a positive predictive value of 38.9%, and a negative predictive value of 99.1% with regard to hospital death using variables selected by the stepwise method. In the extrinsic cause group, D-dimer demonstrated a sensitivity of 83.3%, a specificity was 76.0%, a positive predictive value of 22.0%, and a negative predictive value of 98.3% for predicting hospital death with a cut-off value of 10.14μg/ml. The D-dimer level of patients upon their arrival to emergency rooms is an important factor for predicting patient prognosis. Although multiple factors were related to prognosis in the intrinsic cause group, a 10.14μg/ml D-dimer level may be a good indicator of high-risk patients.

Usefulness of Soluble Concentrations of Interleukin Family Member ST2 as Predictor of Mortality in Patients With Acutely Decompensated Heart Failure Relative to Left Ventricular Ejection Fraction

The aim of the present study was to determine whether the risk of mortality associated with the concentration of soluble ST2 (sST2) differs in patients with acutely decompensated heart failure with preserved ejection fraction (HFpEF) compared to patients with systolic heart failure. We prospectively enrolled 447 patients with acutely decompensated heart failure. Blood samples were collected at presentation to determine the sST2 concentration. HFpEF was defined as symptoms or signs of acutely decompensated heart failure and left ventricular ejection fraction of ≥50% on the echocardiogram. The patients were followed up for 1 year, and the vital status was obtained for all. The sST2 concentrations were greater in the patients with systolic heart failure (n = 250) than in those with HFpEF (n = 197) at 0.55 versus 0.38 ng/ml (p <0.001). Receiver operating characteristic curve analyses showed different cutoff point values for sST2 for the prediction of 1-year mortality in patients with HFpEF (>0.35 ng/ml) and systolic heart failure (>0.56 mg//ml). These cutoff points had similar prognostic accuracy (area under the curve of 0.69 vs 0.73; p >0.05). In the adjusted analyses that included amino terminal B-type natriuretic peptide concentrations, elevated sST2 concentrations were associated with a greater mortality risk in both populations (HFpEF, per ng/ml, hazard ratio 1.41, 95% confidence interval 1.14 to 1.76, p = 0.002; and systolic heart failure, per ng/ml, hazard ratio 1.20, 95% confidence interval 1.10 to 1.32, p <0.001). The determination of the sST2 concentration improved the clinical risk prediction compared to amino terminal B-type natriuretic peptide, as assessed by both the improved C-statistic and an improvement in the net reclassification index and integrated discrimination improvement analyses. In conclusion, in the present multicenter study, sST2 concentrations were lower in patients with HfpEF; however, sST2 remained an independent predictor of mortality, regardless of the left ventricular ejection fraction.

Less Frequent Opening of the Aortic Valve and a Continuous Flow Pump Are Risk Factors for Postoperative Onset of Aortic Insufficiency in Patients With a Left Ventricular Assist Device

Postoperative development of aortic insufficiency (AI) after implantation of left ventricular assist devices (LVADs) has recently been recognized, but the devices in the previous reports have been limited to the HeartMate I or II. The purposes of this study were to determine whether AI develops with other types of LVADs and to elucidate the factors associated with the development of AI. Thirty-seven patients receiving LVADs without evident abnormalities in native aortic valves were enrolled (pulsatile flow LVAD [TOYOBO]: 76%, continuous flow LVAD [EVAHEART, DuraHeart, Jarvik2000, HeartMate II]: 24%). Frequency of aortic valve opening and grade of AI were evaluated by the most recent echocardiography during LVAD support. None of the patients had more than trace AI preoperatively. During LVAD support AI >- grade 2 developed in 9 patients (24%) across all 5 types of devices. More severe grade of AI correlated with higher plasma B-type natriuretic peptide concentration (r = 0.53, P < 0.01) and with less frequent of the aortic valve (r = 0.45, P < 0.01). Multivariate analysis revealed that lower preoperative left ventricular ejection fraction and a continuous flow device type were independent risk factors for higher incidence of AI. AI, which is hemodynamically significant, develops after implantation of various types of LVADs. Physicians need to be more alert to the development of AI particularly with continuous flow devices.

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.

Midregional Pro–Atrial Natriuretic Peptide for the Diagnosis of Cardiac-Related Dyspnea according to Renal Function in the Emergency Department: A Comparison with B-Type Natriuretic Peptide (BNP) and N-Terminal ProBNP

Although renal dysfunction influences the threshold values of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in diagnosis of cardiac-related dyspnea (CRD), its effects on midregional pro-atrial natriuretic peptide (MR-proANP) threshold values are unknown. We evaluated the impact of renal function on MR-proANP concentrations and compared our results to those of BNP and NT-proBNP. MR-proANP, BNP, and NT-proBNP concentrations were measured in blood samples collected routinely from dyspneic patients admitted to the emergency department. Patients were subdivided into tertiles based on their estimated glomerular filtration rate [eGFR, in mL · min(-1) · (1.73 m(2))(-1)]: tertiles 1 (<44.3), 2 (44.3-58.5), and 3 (≥58.6). Of 378 patients studied, 69% (n = 260) had impaired renal function [<60 mL · min(-1) · (1.73 m(2))(-1)] and 30% (n = 114) had CRD. MR-proANP, BNP, and NT-proBNP concentrations were significantly increased in patients with impaired renal function. In each tertile, all peptides remained significantly increased in CRD patients by comparison with non-CRD patients. By ROC analysis, MR-proANP, BNP, and NT-proBNP threshold values for the diagnosis of CRD increased as eGFR decreased from tertile 3 to tertile 1. Areas under the ROC curve for all peptides were significantly lower in tertile 1. Using adapted thresholds, MR-proANP, BNP, and NT-proBNP remained independently predictive of CRD, even in tertile 1 patients. Renal function influences optimum cutoff points of MR-proANP for the diagnosis of CRD. With use of an optimum threshold value adapted to the eGFR category, MR-proANP remains as effective as BNP and NT-proBNP in independently predicting a diagnosis of CRD in the emergency department.

Postoperative Increase in B-Type Natriuretic Peptide Levels Predicts Adverse Outcome After Cardiac Surgery

To evaluate the prognostic implication of changes in postoperative B-type natriuretic peptide (BNP) concentrations in patients undergoing cardiopulmonary bypass for cardiac surgery. A retrospective analysis of prospectively collected clinical data. Cardiothoracic surgery and an intensive care unit (ICU) in a university hospital. The present study included a total of 407 consecutive patients undergoing cardiac surgery. None. BNP concentrations were measured on admittance to the ICU (D0) and at day 1 after surgery. Patients were divided into quintiles according to their BNP level on admittance to the ICU. The predictive value of absolute changes in BNP levels during the first 24 hours postoperatively was analyzed with Kaplan-Meier estimates of survival and Cox multivariate proportional analysis. Prognostic factors for impaired midterm survival included elevation of the BNP level (HR, 7.3/ log10(x); 95% confidence interval, 1.8-29, p = 0.005). The BNP levels of patients undergoing isolated valve surgery or valve and concomitant CABG surgery were significantly higher (p = 0.012 and p = 0.032, respectively) than those undergoing isolated coronary artery bypass graft surgery. Patients in higher quintiles required ventilation for a longer time (p < 0.001), and prolonged inotropic support (p < 0.001). The mean plasma BNP concentration of 172 pg/mL (median, 64; interquartile range, 172) on arrival at the ICU had a sensitivity of 75% and a specificity of 74% for predicting 1-year mortality. Elevated BNP levels on admittance to the ICU and postoperatively increasing BNP levels are associated with adverse postoperative outcome and are predictive of impaired late survival. Sequential postoperative BNP monitoring facilitates the early identification of patients at an increased risk of heart failure and may be used as an adjunct for clinical decision making and optimized patient management.

Serial Monitoring of B-Type Natriuretic Peptide in Management of Heart Failure After Liver Transplantation in a Patient With Budd-Chiari Syndrome: Case Report

Liver transplantation (LT) is an effective treatment option in patients with Budd-Chiari syndrome and end-stage liver disease. However, the procedure may lead to a sudden increase in cardiac preload, which in turn may cause heart failure. Although assays of B-type natriuretic peptide (BNP) are increasingly used in diagnosis, management, and prediction of heart failure, the role of BNP after LT has not been well defined. Herein, we describe the case of a 56-year-old woman with Budd-Chiari syndrome who underwent LT and in whom heart failure was successfully managed using serial monitoring of BNP concentrations. The BNP concentration increased to 1735 pg/mL on postoperative day 4, and decreased to 180 pg/mL on postoperative day 19, at which time inotropic agents were discontinued.

Prediction of cardiogenic shock using plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations in ST elevation myocardial infarction: An analysis from the ASSENT-4 Percutaneous Coronary Intervention Trial

Cardiogenic shock is a major cause of death in ST elevation myocardial infarction. We investigated whether determination of plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone in the acute phase of ST elevation myocardial infarction could identify patients prone to development of cardiogenic shock. Retrospective analysis of a multicenter, randomized open-label trial (ASSENT-4 PCI; ClinicalTrials.gov Identifier: NCT00168792). Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone were determined in available stored samples of 1016 ST elevation myocardial infarction patients without signs of cardiogenic shock at randomization to primary percutaneous coronary intervention or to full-dose tenecteplase before percutaneous coronary intervention. The end point of the present analysis was in-hospital cardiogenic shock. None. In total, 57 (5.6%) patients had cardiogenic shock during index hospitalization. In-hospital cardiogenic shock increased precipitously with higher baseline concentrations of plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone (B-type natriuretic peptide and the N-terminal fragment of its pro-hormone < or =67 pg/mL: 1.9%; 68-1482 pg/mL: 5.9%; >1482 pg/mL: 14.9%; p < .001). Higher plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations were predictors of in-hospital shock, especially among those patients with relatively low clinical risk (no requirement of inotropic support before angiography, systolic blood pressure >100 mm Hg, heart rate <100 bpm, Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score of <122). In multivariate Cox regression analysis, higher plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations remained significant predictors of shock, in addition to age, systolic blood pressure, heart rate, and randomization to facilitated percutaneous coronary intervention and Killip classification. Furthermore, plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone significantly predicted in-hospital shock independently of the validated Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score (p = .014). Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations measured early in the acute phase of ST elevation myocardial infarction are useful in predicting the development of in-hospital cardiogenic shock.

The value of apelin-36 and brain natriuretic peptide measurements in patients with first ST-elevation myocardial infarction

Background We aimed to assess apelin—novel endogenous ligand for the angiotensin-like 1 receptor in patients with ST-elevation myocardial infarction (STEMI) and to compare its value with B-type natriuretic peptide (BNP). Methods In 78 consecutive patients with first STEMI treated with primary PCI, plasma apelin-36 (RIA) and BNP (MEIA) concentrations were measured twice: on admission and on the fifth day of hospitalization. Left ventricle ejection fraction (LVEF) was assessed on admission and composite endpoint (CEP)—after 1 year follow-up. Results During the 5-day interval median plasma BNP level significantly increased and median plasma apelin concentration significantly decreased. BNP, but not apelin, correlated with low LVEF (< 50%). In ROC analysis only BNP measurements were diagnostic for low LVEF. In ANOVA test, in patients with CEP, a significant decrease in apelin (but not BNP) concentrations measured in 5-day interval was found. ROC analysis identified only second BNP measurement as significant to estimate adverse outcome 0.627 in the prediction of CEP (95% confidence interval = 0.507–0.736). Conclusion Following STEMI there is a decrease of plasma apelin-36 concentration and an increase of plasma BNP concentration. BNP is better, than apelin diagnostic value for the detection of impaired LVEF. Both BNP and apelin have prognostic value, although both needs further evaluation.

B-type natriuretic peptide levels and cardiovascular risk in patients with diastolic dysfunction on chronic haemodialysis: cross-sectional and observational studies

Elevated B-type natriuretic peptide (BNP) levels are predictive of cardiovascular events in patients on chronic maintenance haemodialysis, even in those without apparent cardiovascular disorders when they start dialysis. In the present study, we tested the hypothesis that left ventricular diastolic dysfunction increases BNP levels and can predict cardiovascular events in patients on chronic haemodialysis without apparent cardiac disease. Patients on chronic maintenance haemodialysis in a stable condition and with normal systolic function were enrolled (n=98). BNP concentrations were measured, and left ventricular diastolic function was assessed using echocardiography after the first dialysis session of the week. Then, they were followed up for 2 years with the end point being the incidence of cardiovascular events. At baseline, left ventricular diastolic dysfunction was detected in 39 of 98 patients. After adjustment for known risk factors, multivariable regression analysis demonstrated that diastolic dysfunction was a significant predictor of increased BNP levels (P<0.05). During the follow-up period, 17 patients experienced cardiovascular events. Kaplan-Meier analysis demonstrated that the incidence of cardiovascular events was higher in patients with (28.2%) than without (10.2%) left ventricular diastolic dysfunction (log-rank, P<0.01). Univariate Cox proportional hazards regression analysis indicated that diastolic dysfunction and BNP were significant predictors of cardiovascular events (hazard ratio 3.63 and 4.87, respectively; P<0.05). Left ventricular diastolic dysfunction is associated with increased BNP levels and an increased risk of cardiovascular events in patients on haemodialysis.

Cardio-renal interaction: impact of renal function and anemia on the outcome of chronic heart failure

The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.

Circulating biomarkers of tissue remodelling in pulmonary hypertension

Objective: Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role.Methods: We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed.Results: In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy.Conclusion: Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.

Use of Myeloperoxidase for Risk Stratification in Acute Heart Failure

Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF). We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses. MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (< or = 99 vs >99 pmol/L) and BNP (median of < or = 847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045). MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.

Exercise-Induced Natriuretic Peptide Secretion Predicts Cardioversion Outcome in Patients with Persistent Atrial Fibrillation: Discordant ANP and B-Type Natriuretic Peptide Response to Exercise Testing

Measurement of natriuretic peptide's (NP) release in response to hemodynamic stress may be complementary to its baseline assessment in individuals. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) increase in patients with atrial fibrillation (AF) and decrease after successful cardioversion, suggesting that AF may stimulate secretion of NPs. However, there are conflicting data on the predictive value of NPs on the cardioversion outcome. The purpose of this study was to investigate whether baseline and exercise-induced NP plasma levels can be useful in predicting successful cardioversion of persistent AF and maintenance of sinus rhythm during 6-month follow-up. A prospective study enrolled 77 consecutive subjects with persistent AF with normal left ventricular function, referred for elective cardioversion. Patients underwent a modified Bruce protocol treadmill exercise test 24 hours before cardioversion. Blood samples for ANP and BNP analyses were obtained at rest and 5 minutes after exercise peak. The group of successful cardioversion and stable sinus rhythm presented higher exercise ANP (110.6 ± 41.2 pg/mL vs 43.8 ± 36.1; pg/mL, P < 0.0001) and lower BNP increase (5.2 ± 5.2 pg/mL vs 40.5 ± 34.2 pg/mL, P < 0.0001) than the group of unsuccessful cardioversion or AF recurrence. Using an optimized cutoff level of ≤12% of relative exercise-induced increase in BNP concentration, and of >50 pg/mL of ANP increase, successful cardioversion can be predicted with high accuracy. An increase in ANP and stability of BNP plasma concentration during exercise testing are independently associated with successful cardioversion and maintenance of sinus rhythm during 6-month follow-up. (PACE 2010; 33:1203-1209).

Release of N-terminal pro-brain natriuretic peptide in children with acute rheumatic carditis

Acute rheumatic carditis is still an important cause of cardiac failure in developing countries. B-type natriuretic peptides, especially N-terminal segment of its prohormone are now recognised as essential parts of cardiologic evaluation. Increased plasma concentrations of B-type natriuretic peptide and its prohormone are markers of cardiac failure and hypoxia in adults. To measure the prohormone levels in children with acute rheumatic carditis and to determine whether its concentrations correlate with clinical and laboratory findings. A total of 24 children with acute rheumatic carditis and 23 age and sex-matched healthy subjects were entered in the study. Transthoracic echocardiography was performed in all patients to assess the severity of the valve insufficiency and cardiac dysfunction. The prohormone plasma levels were tested for correlation with cardiac dysfunction and other biochemical markers, such as C-reactive protein, erythrocyte sedimentation rate, and anti-streptolysin-O titter. The prohormone plasma concentrations were significantly higher in children with acute rheumatic carditis than in control subjects at the time of diagnosis. A significant decrease of the plasma level was detected among patients after treatments (6-8 weeks). We found increased plasma prohormone levels in children with acute rheumatic carditis in the acute stage of illness compared with healthy subjects. Another result is increased plasma prohormone levels as acute rheumatic carditis are reversible.

How useful are B-type natriuretic peptide measurements for monitoring changes in patent ductus arteriosus shunt magnitude?

Although B-type natriuretic peptide (BNP) concentrations seem to be useful for detecting the presence of patent ductus arteriosus, there is no information about their usefulness for monitoring changes in PDA shunt magnitude. We performed a retrospective analysis of paired BNP-echocardiogram measurements (obtained from infants (24 to 32 weeks gestation) with clinical suspicion of PDA). Individual BNP concentrations (n=146, from 88 infants) were significantly related to shunt magnitude at the time of measurement and had good discriminating power for detecting a moderate-or-large shunt (area under receiver-operator characteristic curves (ROC-AUC)=0.85). In total, 36 infants had serial BNP-echocardiogram pairs (n=91) measured during their hospitalization. Changes (either increases or decreases) in BNP concentrations over time had only fair discriminating power (ROC-AUC=0.76) for detecting increases or decreases, respectively, in shunt magnitude. The high degree of variability in the BNP measurements made them less useful for monitoring changes in magnitude.