Plasma B-type Natriuretic Peptide Concentration Research Articles

Utility of perioperative B-type natriuretic peptide in off-pump bypass surgery

Background and Aims: This study was performed to determine clinical relevance of perioperative B-type natriuretic peptide (BNP) in patients undergoing off-pump coronary artery bypass grafting. Methods: 145 consecutive patients undergoing off-pump coronary artery bypass grafting during 8-month period were enrolled in this study. The relationship between the plasma BNP and various clinical parameters was examined. Postoperatively their main clinical endpoints including requirement of mechanical ventilator support, length of intensive care unit stay and hospital stay was closely monitored. Results: Mean preoperative BNP levels were significantly higher in patients whose left ventricular ejection fraction was less than 0.50 (P<0.00083), and New York Heart Association class (III, IV) (P<0.02). The determinants of preoperative higher level of BNP can be related to the advanced age of the patients, r=0.387 (P<0.01) and left ventricular end diastolic diameter, r=0.200 (P<0.05). Postoperative 12-hour BNP correlated significantly with the duration of mechanical ventilation, rho=0.84 (P<0.05), and postoperative hospital stay for 10 days or more, rho=0.202 (P<0.05). Logistic regression analyses showed a significant association between 12-hour BNP and the requirement of mechanical ventilation, Wald=3.956 (P<0.049, 95% CI_1.023- 20.476). Conclusion: Plasma BNP concentration is a valuable biochemical marker, is easy to measure and can effectively predict postoperative outcome in off-pump coronary artery bypass grafting. Baseline BNP had strong correlation with the age and ventricular function of the patient. Postoperatively, elevated 12-hour BNP indicated prolonged ventilation and longer duration of hospital stay. DOI: http://dx.doi.org/10.3126/njh.v11i1.10977 Nepalese Heart Journal 2014;11(1): 19-25

Central pulse pressure links microalbuminuria with plasma B-type natriuretic peptide elevation: causal implication for cardiorenal syndrome in hypertension.

A pathological connection between the heart and kidney is well recognized as a cardiorenal syndrome, but the underlying mechanism remains undetermined. We hypothesized that this connection is attributable to central haemodynamic alterations. In 386 patients with hypertension, the radial, carotid and femoral pressure waveforms were recorded with applanation tonometry to estimate the aortic pressure and pulse wave velocity (PWV). The plasma B-type natriuretic peptide (BNP) concentration and urinary albumin/creatinine ratio (UACR), cardiac and renal damage biomarkers, respectively, were also measured for each patient. The BNP was correlated positively with UACR, aortic pulse pressure and PWV, but inversely with the estimated glomerular filtration rate (eGFR, P < 0.001). The aortic pulse pressure tended to more closely correlate with BNP than the brachial pulse pressure. The presence of (micro)albuminuria (UACR ≥30 mg/g) was associated with BNP elevation (≥50 pg/ml) independently of age, BMI, mean arterial pressure, eGFR and β-blocker treatment (odds ratio: 2.41; P = 0.04). However, further adjustment for the aortic pulse pressure or PWV rendered this albuminuria-BNP relationship insignificant (P = 0.25) and, instead, the aortic pulse pressure emerged as the strongest determinant of BNP elevation (odds ratio: 1.51 per 10mmHg; P = 0.001). Differently from albuminuria, lower eGFR was consistently related to higher plasma BNP, even after controlling for the aortic pressure and PWV. Concomitant plasma BNP elevation with (micro)albuminuria can be explained by increases in aortic pulse pressure and PWV. This finding suggests that the altered central haemodynamics causes simultaneous damage/dysfunction in the heart and kidney, which could then contribute to cardiorenal syndrome in hypertension.

Natriuretic peptides buffer renin-dependent hypertension

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

Long-term advanced therapy with bosentan improves symptoms and prevents deterioration of inoperable chronic thromboembolic pulmonary hypertension

AimsChronic thromboembolic pulmonary hypertension (CTEPH) is a devastating disease, and treating patients with CTEPH who are not eligible for pulmonary endarterectomy is particularly challenging. Short-term bosentan or phosphodiesterase type-5-inhibitor treatment can greatly improve symptoms and hemodynamics in these patients; however, the long-term benefits of advanced pulmonary vasodilators are not known. We retrospectively investigated the long-term effects of advanced pharmacological therapy in Japanese patients with inoperable CTEPH. Main methodsSeven consecutive patients with inoperable CTEPH (five women; mean age, 62.6±6.9years) treated with bosentan were included. World Health Organization functional class (WHO-FC), hemodynamics, exercise capacity, and plasma B-type natriuretic peptide (BNP) concentration were evaluated at baseline and for more than 2years. Time to clinical worsening was also examined during long-term follow-up. Key findingsWHO-FC improved significantly, from 3.1±0.4 to 2.1±0.4 (p=0.005). Significant improvement was also seen in pulmonary vascular resistance, which decreased from 786.9±300.0 to 352.2±210.7dynesscm−5 (p<0.05). Plasma BNP concentration decreased significantly from 1160.0±971.4 to 305.1±285.9pg/mL (p<0.05). No patient required hospitalization during the follow-up period (mean, 896±564days). SignificanceLong-term advanced therapy with bosentan significantly improves symptoms, pulmonary vascular resistance, plasma BNP concentration, and time to clinical worsening in Japanese patients with inoperable CTEPH. We consider bosentan to be an essential treatment for these patients.

Kidney function crucially affects B‐type natriuretic peptide (BNP), N‐terminal proBNP and their relationship

B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful biomarkers in the management of heart failure. Both peptides are secreted into the circulation after cleavage of their precursor proBNP and excreted from the kidney in the active form or as metabolites. We investigated effects of kidney function on the levels and association of these peptides. Plasma concentrations of BNP and serum concentrations of NT-proBNP were measured in 229 outpatients of our cardiology department (male/female = 138/91, mean age= 68 years) and 53 hospital outpatients on chronic haemodialysis (30/23, 68 years). Kidney function in nondialysed patients was assessed by estimated glomerular filtration rate (eGFR; mL/min/1.73 m(2)) and categorised across five stages. Effects of kidney function on BNP, NT-proBNP and their relationship were investigated. Deterioration in kidney function increased BNP and NT-proBNP levels, as well as the NT-proBNP/BNP ratio, and these values were highest in patients on haemodialysis. The eGFR inversely correlated with BNP (r = -0.472), NT-proBNP (r = -0.579), and the NT-proBNP/BNP ratio (r = -0.454, all P < 0.0001). A significant correlation was observed between BNP and NT-proBNP at all stages of kidney function including patients on haemodialysis, but the correlation was significantly affected by kidney function. Although circulating levels of both BNP and NT-proBNP increased with deteriorating kidney function, the impact of kidney function on NT-proBNP was much more pronounced than that on BNP. Kidney function should be taken into account when interpreting data on BNP, NT-proBNP and their relationship.

Association of plasma B-type natriuretic peptide concentration with myocardial infarct size in patients with acute myocardial infarction

B-type natriuretic peptide (BNP) is widely used in the treatment of early-stage heart failure and coronary heart disease. In this study, the association of plasma BNP concentration with myocardial infarct (MI) size in patients with acute myocardial infarction (AMI) was investigated. Eighty patients with AMI were enrolled in the MI group and 30 healthy volunteers were selected as the control group. Magnetic resonance imaging of the heart and plasma BNP concentration detection were carried out, and then the relationship between plasma BNP concentration and MI size was analyzed in the two groups. Results showed that the plasma BNP concentration was positively related to MI size (r = 0.645, P < 0.0005), whereas it was negatively correlated to the left ventriculus ejection fraction (r = 0.297, P = 0.047). Multiple regression analysis showed that MI size was the only parameter that was independently associated with BNP (r(2) = 0.32, F = 7.712, P = 0.007). Moreover, when the BNP level reached 150 pg/mL, it had 85.1% sensitivity and 70.4% specificity of determining MI sizes exceeding 10%. The plasma concentration of BNP is highly related to MI size in patients with AMI, and can be clinically used to evaluate MI size.

New insights into the mechanisms involved in B-type natriuretic peptide elevation and its prognostic value in septic patients.

IntroductionElevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.MethodsIn this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.ResultsA total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).Twenty-eight-day mortality was 47.6% (20 of 42 patients). Daily BNP values poorly predicted outcome; BNP on day 1 > 800 pg/ml (the best cutoff point) fairly predicted mortality, with a sensitivity%, specificity% and area under the curve values of 65, 64 and 0.70, respectively (95% confidence interval = 0.54 to 0.86; P = 0.03). Plasma BNP levels declined faster in survivors than in nonsurvivors in both critical sepsis and septic shock (P ≤0.002). In septic shock, a BNP/CVP ratio >126 pg/mmHg/ml on day 2 and inability to reduce BNP <500 pg/ml implied increased mortality (P ≤0.036).ConclusionsThe severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.

Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients

IntroductionCardio-renal syndromes are characterized by the impairment of cardiac and renal functions. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL), and plasma B-type natriuretic peptide (BNP) are markers of acute kidney injury (AKI) and heart failure (HF), respectively.The aim of this study was to assess the effect of the reduction of glomerular filtration rate (GFR) on plasma BNP and on plasma and urinary NGAL concentrations in stable chronic kidney disease (CKD) patients at different functional stages.MethodsGFR (99mTc-DTPA), plasma BNP, and plasma and urinary concentrations of NGAL were measured in 310 clinically stable CKD patients, at functional stages from 1 to 5. Serum and urinary low-molecular-weight proteins cystatin C and β2-microglobulin, and urinary tubular enzymes were measured for comparison. Plasma BNP, NGAL, cystatin C and β2-microglobulin were measured also in 31 maintenance hemodialysis patients.ResultsPlasma NGAL increased with the reduction of GFR in CKD patients from stage 2. In the different CKD stages modest differences were found for BNP values. Urinary NGAL increased slightly but significantly in patients at CKD stages 4 and 5, similarly to urinary cystatin C and β2-microglobulin. In maintenance hemodialysis patients, plasma NGAL and BNP were markedly increased, and high-flux hemodialysis significantly decreased their plasma concentrations.ConclusionsPlasma NGAL increases markedly with the reduction in GFR, generating a very high number of false positive diagnoses of AKI in stable CKD patients. The grade of GFR impairment and the cause of kidney disease have a lower effect on urinary NGAL and on plasma BNP. In any case, specific reference values of NGAL and BNP should be used in chronic kidney disease patients, according to their functional stage, when assessing acute kidney injury, heart failure, and cardio-renal syndromes in patients with impaired GFR.

B-type natriuretic peptide levels in preterm neonates with bronchopulmonary dysplasia: A marker of severity?

B type natriuretic peptide (BNP) is a hormone released in response to stretching of the ventricular wall. The role of BNP as a biomarker of bronchopulmonary dysplasia (BPD) has not been clarified. To determine if plasma BNP concentrations correlate with the severity of BPD. This prospective observational case control study included 60 preterm infants (≤32 weeks); 27 infants had no/mild BPD, 19 had moderate and 14 had severe BPD. BNP levels were measured at 36 ± 2 weeks PMA or within a week of discharge home. Groups were compared using Mann-Whitney's U-test, Kruskal-Wallis, and bivariate regression. Median (IQR) plasma levels of BNP in infants with moderate/severe BPD infants (n = 33) were higher as compared to those with no/mild BPD (n = 27); 27.1 (12.1-43.5) pg/ml versus 9.3 (6-18.5) pg/ml; P < 0.05 (Mann Whitney U). Median (IQR) BNP levels in infants with severe BPD (n = 14), 43.5 (28.4-189) pg/ml differed significantly from levels in those with moderate (n = 19), 22.8 (10.3-27.7) pg/ml; mild (n = 16), 11.5 (6.6-44.5 pg/ml); or no (n = 11), 8.1 (5-12.6 pg/ml) BPD (P < 0.001 Kruskal-Wallis). Based on receiver operating characteristic curves, BNP > 24.4 pg/ml at 36 ± 2 weeks PMA or discharge home was 85.7% sensitive and 76.1% specific for severe BPD. An elevation in plasma BNP was significantly associated with severe BPD. We speculate that plasma BNP measurement in infants with BPD may aid in risk-stratification and further targeted therapies.

Midregional-pro-adrenomedullin but not copeptin represents a marker of overall ardiopulmonary stress

Background: Midregional pro-adrenomedullin (MR-pro ADM) and C-terminal pro-vasopressin (copeptin) provide prognostic information in a variety of settings. However, little is known about the relationship of these novel bio markers with the cardiopulmonary exercise testing (CPET) response. We sought to assess the relationship between MR-proADM and copeptin and peak oxygen consumption (peak VO2) and other key CPET parameters and to compare it to the established B-type natriuretic peptide (BNP). Methods: In 162 consecutive patients with a broad spectrum of pulmonary and cardiac function undergoing symptom-limited CPET for evaluation of exercise intolerance, MR-proADM, copeptin, and BNP plasma concentrations were measured immediately before CPET. Results: The median (interquartile range) MR-proADM, copeptin and BNP plasma concentration were 0.58 (0.44-0.77) nmol/l, 6.2 (4.5-10.3) pmol/l and 42 (17-103 ng/l) respectively. There were significant inverse correlations between peak VO2 and both MR-proADM and BNP but not copeptin (r= -0.57, p 0.05 for all). Conclusion: High MR-proADM but not copeptin is at least as good an indicator of low peak VO2 as BNP and is a marker of CPET parameters reflecting an impairment of the cardiac output reserve, ventilatory inefficiency, and impaired diffusion capacity, and thereby represents a marker of overall cardiopulmonary stress, which likely explains its strong prognostic value.

Application of adenosine stress echocardiography in the prognosis of acute myocardial infarction following percutaneous coronary interventional therapy

The aim of this study was to investigate the application of adenosine stress echocardiography (ASE) in the prognosis of acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). A total of 79 patients with AMI who underwent PCI were selected for the study. ASE testing was performed within one week following the PCI. Subsequent to the ASE, the patients with ≥5% increases in the left ventricular ejection fraction (LVEF) levels were included in the improved LVEF group, while patients with <5% increases in LVEF levels were included in the unimproved LVEF group. A follow-up study was performed during the 24 months subsequent to the ASE. The incidence of major adverse cardiovascular events (MACEs) was observed and compared between the two groups and logistic regression analysis was applied to identify the risk factors for clinical prognosis. There were no significant differences in Killip classification, LVEF, left ventricular end-diastolic diameter or blood plasma B-type natriuretic peptide concentration between the two groups following PCI. The incidence of MACEs in the improved LVEF group was significantly lower than that in unimproved LVEF group (14.29 versus 43.24%, respectively; P<0.05). Logistic regression analysis identified LVEF increases of <5% and segment improvements of ≤3 as the risk factors for the clinical prognosis of AMI following treatment with PCI. Therefore, ASE is an effective method of assessing the clinical effect of PCI treatment, which may be utilized to predict the incidence of MACEs following PCI.

Fetal Rat Hearts Do Not Display Acute Cardiotoxicity in Response to Maternal Doxorubicin Treatment

Anthracyclines are used to treat cancers during the second and third trimester of pregnancy. The chemotherapeutic effect of anthracyclines is associated with a dose- and time-dependent cardiotoxicity that is well described for infants and adults. However, data regarding fetal anthracycline-related cardiotoxicity after administration of chemotherapeutics during pregnancy are limited. In this study, we analyzed the acute effect of doxorubicin, an anthracycline derivative, on fetal and maternal rat myocardium. We injected 10 or 20 mg/kg i.v. doxorubicin to pregnant Wistar rats at day 18 of pregnancy; age-matched pregnant rats injected with physiologic saline served as controls. Maternal echocardiography and fetal Doppler scanning were performed before the injection and before sacrifice. Cesarean operation was performed at day 19 or 20, and maternal and fetal blood samples and heart biopsies were collected to measure apoptosis, the impact on cell proliferation, and structural cardiac damage. Acute maternal cardiotoxicity is associated with loss of body weight, moderately deteriorated left ventricular function, induction of apoptosis, and a decrease in cell turnover. Despite a 30% lower fetal body weight and elevated plasma B-type natriuretic peptide concentrations after doxorubicin administration, the fetal hearts had intact microstructure, an unaltered number of apoptotic cells, and preserved cell proliferation compared with controls. Our study suggests that acute treatment using anthracyclines during pregnancy impairs maternal cardiac function, whereas fetal hearts are protected.

Effectiveness of Spironolactone Plus Ambrisentan for Treatment of Pulmonary Arterial Hypertension (from the [ARIES] Study 1 and 2 Trials)

In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor-mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan + spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings.

The value of the use of plasma B-type natriuretic peptide among acute ischemic stroke patients in a Chinese emergency department

ObjectiveTo determine the value of the use of plasma B-type natriuretic peptide (BNP) among acute ischemic stroke patients in a Chinese emergency department (ED). Materials and methodsIn our ED, the emergency physicians prospectively assessed consecutive adult patients with acute phase of ischemic stroke and measured plasma BNP by Biosite Triage®BNP POCT platform on admission, then followed up these patients. And the stroke neurologists evaluated patients’ functional outcome at hospital discharge, and also made discharge diagnosis and stroke etiologic subtypes according to TOAST criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-artery occlusion (SAO), stroke of other determined etiology (SOE) and stroke of other undetermined etiology (SUE). ResultsIn this study, 142 of 238 acute ischemic stroke patients met the study criteria [mean age 70.84±11.48 years, 74 (52.11%) female]. Of the 142 patients, 35.92% were diagnosed with LAA at discharge, 25.35% with CE, 27.46% with SAO, 11.27% with SOE or SUE. Age, previous cardiac disease, atrial fibrillation, the length of hospital stays, SSS score on admission≤25 and mRS≥3 or death at discharge were all significantly higher in the CE patients compared to other subtypes (p<0.01). And the mean BNP concentration was significantly higher in the CE group than in other three subtypes (p<0.001). The optimal cut-off concentration, sensitivity and specificity of the plasma BNP concentration suitable to distinguish CE from non-CE were 66.50pg/ml, 75.0% and 88.7%, respectively. ConclusionsPlasma BNP level is significantly higher in CE patients than in other TOAST subtypes, and by using Biosite Triage®BNP POCT platform, emergency physicians should strongly consider CE subtype with the plasma BNP level of over 66.50pg/ml. However, the single BNP biomarker panel cannot be used to confidently rule out or identify stroke subtypes as a diagnosis and must be taken in context with clinical assessment and judgment before making management decisions in the ED.

Tolvaptan Can Improve Clinical Course in Responders

We previously defined "responders" as patients with increases in urine volume (UV) on day 1 after the administration of tolvaptan (TLV), and demonstrated that responders to TLV could be predicted with considerable accuracy by urine osmolality (U-OSM) levels. Responders and non-responders to TLV should be associated with different clinical courses after a certain time following TLV administration. Therefore, the aim of the present study was to validate our definition of responders by clinical parameters 1 week after administration of TLV. Data (n = 85) were obtained from in hospital patients with decompensated heart failure (HF) who had received TLV at 3.75-15 mg daily, and clinical data at 1 week after the administration of TLV were compared with those of baseline. Sixty patients (70.6%) were "responders", in whom UV on day 1 increased after the administration of TLV compared with day 0. "Non-responders" were older, and had higher serum creatinine concentration and lower baseline U-OSM than "responders". Serum creatinine concentration increased significantly in "non-responders", but was unchanged in "responders". Body weight, plasma B-type natriuretic peptide concentration, and HF symptom score decreased significantly in "responders", but remained unchanged in "non-responders". Increases in UV after the first administration of TLV were closely correlated with improvement of congestive HF after 1 week of TLV treatment, which verified our definition of "responders" to TLV.

Dual Renin–angiotensin System Blockade with Aliskiren in Patients with Heart Failure, with or without Diabetes Mellitus: Insights from ALOFT

Aims: Because of recent concerns about the safety of dual renin–angiotensin–aldosterone system (RAAS) blockade with a renin inhibitor in patients with hypertension and diabetes mellitus (DM), we have conducted a retrospective analysis of the effect of this treatment in patients with and without diabetes in the Aliskiren Observation of Heart Failure Treatment study (ALOFT). Methods and results: In ALOFT, patients with stable New York Heart Association class II–IV heart failure (HF) and plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL were randomised to Aliskiren 150 mg/d or placebo, added to optimal HF therapy, for 12 weeks. In addition to greater central adiposity and dysglycaemia, HF patients with DM had more oedema, elevated blood urea and urinary albumin/creatinine ratio, and increased plasma renin activity (PRA) and concentration. They also had evidence of greater left ventricular hypertrophy, increased collagen turnover, left atrial enlargement and mitral regurgitation. Aliskiren had similar effects in patients with and without DM, reducing BNP, NT proBNP and PRA equally in both groups. The incidence of adverse effects related to hypotension, hyperkalaemia and renal dysfunction was low in each patient group and was not increased, significantly, with Aliskiren. Conclusions: HF patients with DM have elevated PRA compared to those without DM. Aliskiren causes equivalent neurohumoral suppression in HF patients with and without DM.

Prediction of atrial fibrillation after ischemic stroke using P-wave signal averaged electrocardiography

BackgroundAtrial fibrillation (AF) is highly prevalent in patients with ischemic stroke, but the diagnosis is often difficult. MethodsThis study consisted of 68 stroke patients in sinus rhythm without history of AF. All patients underwent P-wave signal-averaged electrocardiography (P-SAECG), echocardiography, 24-h Holter monitoring, and measurement of plasma B-type natriuretic peptide (BNP) concentrations at admission. ResultsAn abnormal P-SAECG was found in 34 of 68 stroke patients. In the follow-up period of 11±4 months, AF developed in 17 patients (AF group). The remaining 51 patients were classified as the non-AF group. The prevalence of atrial late potentials (ALP) on P-SAECG, and the number of premature atrial contractions (PACs) were significantly higher in the AF group than those in the non-AF group (88.2% vs 37.3%; p<0.001, 149±120 vs 79±69; p=0.030, respectively). However, there were no significant differences in age, left atrial dimension, or BNP concentrations between both groups. Cox proportional hazards analysis revealed that the presence of ALP (risk ratio 11.15; p=0.002) and frequent PACs (more than 100/24h) (risk ratio 4.53; p=0.007) had significant correlation to the occurrence of AF. ConclusionsALP may be a novel predictor of AF in stroke patients. P-SAECG should be considered in stroke of undetermined etiology.

Natriuretic Peptide–driven Fluid Management during Ventilator Weaning

Difficult weaning from mechanical ventilation is often associated with fluid overload. B-type natriuretic peptide (BNP) has been proposed as a tool for predicting and detecting weaning failure of cardiovascular origin. To investigate whether fluid management guided by daily BNP plasma concentrations improves weaning outcomes compared with empirical therapy dictated by clinical acumen. In a randomized controlled multicenter study, we allocated 304 patients to either a BNP-driven or physician-driven strategy of fluid management during ventilator weaning. To standardize the weaning process, patients in both groups were ventilated with an automatic computer-driven weaning system. The primary end point was time to successful extubation. In the BNP-driven group, furosemide and acetazolamide were given more often and in higher doses than in the control group, resulting in a more negative median (interquartile range) fluid balance during weaning (-2,320 [-4,735, 738] vs. -180 [-2,556, 2,832] ml; P < 0.0001). Time to successful extubation was significantly shorter with the BNP-driven strategy (58.6 [23.3, 139.8] vs. 42.4 [20.8, 107.5] h; P = 0.034). The BNP-driven strategy increased the number of ventilator-free days but did not change length of stay or mortality. The effect on weaning time was strongest in patients with left ventricular systolic dysfunction. The two strategies did not differ significantly regarding electrolyte imbalance, renal failure, or shock. Our results suggest that a BNP-driven fluid management strategy decreases the duration of weaning without increasing adverse events, especially in patients with left ventricular systolic dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT00473148).

Efficacy and Effect on Plasma B-type Natriuretic Peptide Concentration of Losartan-hydrochlorothiazide for Hypertension Uncontrolled by Losartan-based Therapy: Subanalysis of a Multicentre Prospective Observational Study

Many patients with hypertension have difficulty achieving their target blood pressure (BP). Therefore combination therapy, for example with an angiotensin II receptor blocker (ARB) and a diuretic, may be recommended. We previously evaluated the efficacy and safety of losartan (LOS) 50 mg - hydrochlorothiazide (HCTZ) 12.5 mg, as well as its effect on the plasma concentration of B-type natriuretic peptide (BNP, a prognostic marker for cardiovascular events), in patients with hypertension uncontrolled by ≥3 months of ARB-based therapy. The present subanalysis used data from patients who received LOS-based therapy before switching to LOS-HCTZ. Efficacy, safety, and changes in blood biochemical variables including BNP were evaluated. After excluding 4 patients with protocol violations, data from 35 patients (aged 36-79 years, mean 63 years; 66% male) were used in the safety analysis. The efficacy analysis used data from the 30 patients who were followed up for 12 months. Systolic/diastolic BP decreased from 156±12/87±11 mmHg at baseline to 125±11/73±10 mmHg at 12 months (p<0.001). After 12 months, half of the patients achieved their target BP as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2004. In 12 patients with baseline plasma BNP concentration ≥20 pg/mL, BNP decreased from 78.3±18.8 pg/mL to 57.3±17.7 pg/mL (p<0.01). 3 patients experienced adverse events, one of which was cardiovascular. LOS-HCTZ is efficacious, has a good safety profile, and decreases plasma BNP concentration.

The role of brain natriuretic peptide and serum triiodothyronine in the diagnosis and prognosis of chronic heart failure

Objective The objective of this paper was to investigate the diagnostic and prognostic value of plasma B type natriuretic peptide (BNP) and serum triiodothyronine (T3) in chronic congestive heart failure (CHF).Methods 156 cases of CHF patients and 75 cases of cardiac function I patients hospitalized over the same period were utilized in this study. On admission, the patient’s BNP and T3 plasma concentrations were measured. The correlation analysis of plasma BNP and T3 in CHF patients with cardiac function classification was conducted.Results According to the NYHA grading systems, the plasma BNP levels in patients with II, III, and IV grade CHF were significantly higher than those with cardiac function I (P < 0.05); BNP levels and NYHA grading of cardiac function correlated positively. The BNP concentrations increased with CHF progression (P < 0.01). The T3 level and NYHA grading of cardiac function correlated negatively. The T3 level decreased as the degree of heart failure increased. Using CHF in combination with BNP to predict the occurrence of CHF had a sensitivity value of 90.8% with 95.5% specificity, 86.3% accuracy, and a negative predictive value of 87.7%.Conclusions Plasma BNP was more sensitive than T3 in the diagnosis of CHF. The T3 was more meaningful than the BNP in the prognosis of CHF. The BNP and T3 combination detection was more valuable in determining the severity of CHF and prognosis.