Plasma Brain-type Natriuretic Peptide Research Articles

Contrast-associated acute kidney injury and cardiovascular events: a secondary analysis of the PRESERVE cohort.

Contrast-associated acute kidney injury (CA-AKI) has been associated with a higher risk of cardiovascular (CV) events. We studied the risk of CV events in chronic kidney disease (CKD) patients undergoing angiography and whether biomarkers can predict such events. We also explored whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate (eGFR) on CV events. We analysed participants from the Prevention of Serious Adverse Events following the Angiography (PRESERVE) trial. Urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7, plasma brain-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hs-CRP), and serum cardiac troponin-I (Tn-I) were assayed before and after angiography. We assessed the composite risk of CV events by day 90. Of the 922 participants, 119 (12.9%) developed CV events, and 73 (7.9%) developed CA-AKI. Most cases of CA-AKI (90%) were stage 1. There were no differences in urinary [TIMP-2]•[IGFBP7] concentrations or the proportion of patients with CA-AKI among those with and without CV events. Higher BNP, Tn-I, and hs-CRP were associated with CV events, but their discriminatory capacity was modest (AUROC <0.7). CA-AKI did not mediate the association of the pre-angiography eGFR on CV events. Most episodes of CA-AKI are stage 1 AKI and are not associated with CV events. Less severe CA-AKI episodes also did not mediate the risk of pre-angiography eGFR on CV events. Our findings suggest that most CV events after contrast procedures are due to underlying CKD and CV risk factors rather than less severe CA-AKI episodes and should help enhance the utilization of clinically indicated contrast procedures among high-risk patients with CKD. Further research is required to examine whether moderate-to-severe CA-AKI episodes are associated with CV events.

P2634Prognostic value of admission left ventricular outflow tract velocity time integral in hospitalized heart failure patients with preserved ejection fraction: a report from the JASPER registry

Abstract Background There are little effective treatment strategies for heart failure with preserved ejection fraction (HFpEF) to achieve a reduction of morbidity and mortality. Thus, accurate prognostication of patients with HFpEF could help improve their outcomes by identifying high-risk patients who might potentially benefit from intensive inpatient and outpatient monitoring and early referral for advanced HFpEF therapy. The left ventricular outflow tract velocity time integral (LVOT-VTI) is a representative non-invasive parameter for evaluating stroke volume, which can be a determinant of adverse outcomes in hospitalized patients with heart failure. However, the prognostic implication of admission LVOT-VTI for hospitalized HFpEF patients is undetermined. Purpose The aim of the present study was to investigate whether admission LVOT-VTI could predict poor clinical outcomes in hospitalized patients with HFpEF. Methods We examined consecutive 535 hospitalized HFpEF patients (left ventricular ejection fraction ≥50%) due to acute decompensated heart failure from the JASPER (JApanese heart failure Syndrome with Preserved Ejection fRaction) multicenter registry, obtained between November 2012 and March 2015. Patients without accessible LVOT-VTI data on admission were excluded. Finally, 214 patients were examined. The primary outcome of interest was composite of all-cause death and rehospitalization due to heart failure. Results Mean age was 78±11 years, 100 were male, and median plasma brain-type natriuretic peptide level was 400 (interquartile range [IQR] 223–711) pg/ml. During a median follow-up period of 688 (IQR 162–810) days, adverse events occurred in 83 patients (39%), including 47 (22%) all-cause death, 51 (24%) rehospitalization due to heart failure. The c-index of LVOT-VTI for predicting the composite of adverse events was 0.59 (95% CI 0.51 to 0.67), and the optimal cut-off value of LVOT-VTI was 15.8 cm. Low LVOT-VTI (≤15.8 cm) was significantly associated with higher adverse events compared to high LVOT-VTI (&gt;15.8 cm) (Figure). Multivariable Cox regression analysis revealed that lower LVOT-VTI was an independent determinant of adverse events (HR 0.94, 95% CI 0.91 to 0.98, P=0.005) even after adjustment for pre-specified confounders including age, sex, systolic blood pressure, serum sodium, albumin, plasma brain-type natriuretic peptide and renal function. Figure 1 Conclusions Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission could be a useful marker for risk stratification in these patients.

Role of brain-type natriuretic peptide in rapid diagnosis and prognosis of persistent pulmonary hypertension of the newborn

Objective The diagnosis of persistent pulmonary hypertension of the newborn (PPHN) can often be difficult to make, especially in a clinical setting in which pediatric echocardiography is not readily available. This study aims at investigating the value of plasma brain-type natriuretic peptide (BNP) level as a noninvasive test in the diagnosis, prognosis, and differentiation of PPHN from other respiratory diseases in newborns with respiratory distress (RD). Patients and methods We used a prospective cohort study with three groups. One group was diagnosed with PPHN by clinical and echocardiographic criteria (PPHN group: n=20). The second group had been diagnosed with respiratory disease; however, PPHN was ruled out by having no evidence of elevated pulmonary pressure by echocardiography (RD group: n=20). The third group had no respiratory disease and was breathing room air (RA group: n=20). Plasma BNP levels were measured by Ray Bio BNP Enzyme Immunoassay Kit at study entry for all groups and upon recovery for PPHN cases. Results There was no difference between groups regarding gestational age, postnatal age, sex, birth weight, and mode of delivery. Initial BNP levels (pg/ml) were significantly elevated in the PPHN group relative to both the RA and RD groups. There was no difference in the initial plasma BNP level between the RD and RA groups. Plasma BNP levels declined significantly in the PPHN group upon recovery. Plasma BNP levels correlated with the gradient of the tricuspid regurgitation jet and the mean pulmonary artery pressure. Plasma BNP levels were higher, although insignificant, in PPHN because of underdevelopment. The mean plasma BNP level in septic babies was higher; however, this was insignificant, still the number of cases was low (two cases). Conclusion Plasma BNP levels were elevated in infants with PPHN but not in infants with other forms of RD. Follow-up plasma BNP level showed significant decline after recovery of PPHN cases. Elevated plasma BNP levels in term or near-term infants with RD should increase the suspicion of PPHN.

Left ventricular stiffness estimated by diastolic wall strain is associated with paroxysmal atrial fibrillation in structurally normal hearts.

Left ventricular (LV) diastolic dysfunction depends on an impaired relaxation and stiffness. Abnormal LV relaxation contributes to the development of atrial fibrillation (AF), but the role of LV stiffness in AF remains unclear. Diastolic wall strain (DWS), a load-independent, noninvasive direct measure of LV stiffness, correlates with prevalent AF. This study included 328 consecutive subjects with structurally normal hearts: 164 paroxysmal AF patients and 164 age- and sex-matched (1:1) controls. We calculated the DWS from the M-mode echocardiographic measurements of the LV posterior wall thickness at end-systole and end-diastole during sinus rhythm. The DWS was lower in the AF patients (0.35 ± 0.07) than in the controls (0.41 ± 0.06; P < 0.001). After adjusting for the risk factors of AF using a conditional logistic regression analysis, a history of hypertension, plasma brain-type natriuretic peptide level, and DWS were independently associated with AF prevalence, whereas body mass index, LV mass index, left atrial volume, and any conventional indices of the diastolic function were not. A low DWS (<0.380) was the strongest indicator of AF (odds ratio: 6.22, 95% confidence interval: 3.08-14.2, P < 0.001). Increased LV stiffness estimated by DWS was a strong determinant of the prevalence of AF. LV stiffness may play a role in the pathogenesis of paroxysmal AF in structurally normal hearts.

Plasma brain-type natriuretic Peptide level following seizure and syncope: pilot study.

To explore the clinical feasibility of plasma brain-type natriuretic peptide (proBNP) level to differentiate the two major causes of transient unconsciousness, seizure and vasovagal syncope (VVS) in adult patients. ProBNP levels were evaluated within 24 hours following attack in patients who had experienced a transient episode of unconsciousness. For confirmatory diagnosis, clinical history was reviewed thoroughly and several work-ups including electroencephalography and cerebral imaging and tilt-table test, were performed in cases of putative VVS, as a part of routine clinical approaches. According to various relevant evaluations, 15 patients were diagnosed as seizure (age, 40.3±13.8 years) and 12 patients were VVS (age, 38.1±17.1 years). Plasma concentrations of pro-BNP were not different between two groups (p=0.714). Median level was 34.3 pg/mL (interquartile range: 12.9-91.1) in post-seizure group and 32.3 pg/mL (interquartile range 8.9-77.4) in post-VVS group. Additionally, it was not correlated with the sampling times within 24 hours after the episodes. The plasma level of pro-BNP has a limited clinical value in differentiating seizure and vasovagal syncope in adults. However, the more validated results with a large population should be sought in the future studies to confirm its value.

Brain natriuretic peptide is released from human astrocytoma cell line U373MG under hypoxia: a possible role in anti-apoptosis

We have recently shown that the plasma brain-type natriuretic peptide (BNP) level is elevated in acute ischemic stroke patients, but the origin and role of BNP remain unclear. We investigated whether human astrocytes secrete BNP under hypoxia, and if so, what signaling pathway is involved, and what is the role of BNP. Human astrocytoma cell line U373MG was exposed to hypoxia by Anaeropack. BNP gene expression was increased by 3.9±2.5- and 6.5±2.9-fold at 12 and 24 h after hypoxia respectively (n=6, both P<0.05) and was associated with twofold increase in BNP protein at 24 h. BNP release in the culture media (pg/mg protein) was elevated from 1.8±1.8 under normoxia to 13.5±7.8 after 24-h hypoxia (n=9, P<0.01 versus normoxia). Western blot revealed the tyrosine⁴¹⁵ phosphorylation of tyrosine kinase c-Src under hypoxia. Treatment of the cells with tyrosine kinase inhibitor PP1 abolished hypoxia-induced increase in BNP expression and release. In the cells exposed to hypoxia, caspase activity and apoptosis, measured by annexin-V-propidium iodide kit, were increased at 24 h compared with the cells under normoxia (n=5, both P<0.05). It was further increased in the cells transfected with siRNA for natriuretic peptide precursor B (n=6, both P<0.05) and reversed by administration of exogenous BNP (P<0.01). In conclusion, hypoxia increased BNP expression and release in human astrocytoma cell line U373MG through c-Src activation. BNP may play a pivotal role in anti-apoptosis of astrocytes under hypoxia.

Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin

Objective. This study sought to determine the effect of combined treatment of hypoxia plus indomethacin on pulmonary vascular remodeling in fetal rats.Methods. Hypoxia and indomethacin were used to treat pregnant rats during 19–21 days of gestation. The adventitia, media, and intima of pulmonary arteries from fetal rats were assessed. Western blots were used for determining the abundance of smooth muscle specific alpha-actin protein (α-SMA), elastin, and endothelial nitric oxide synthase (eNOS) in lung tissues. Plasma brain-type natriuretic peptide (BNP) levels, reflecting the increased right ventricular load or pulmonary arterial pressure, were detected.Results. The ratio of left ventricular free wall plus septum to right ventricular weight significantly increased in hypoxia plus indomethacin-treated group. The medial thickness percentage of pulmonary arteries of < 100 μm and ≥100 μm in diameter from hypoxia plus indomethacin-treated group was higher than that from control or single treatment group. Vascular elastin area percentage and immunostaining density of eNOS from the combined-treated group were higher than other groups. The relative abundance of α-SMA, elastin, and eNOS and plasma BNP levels in hypoxia plus indomethacin-treated group also significantly increased compared with other groups.Conclusions. Hypoxia and indomethacin had synergistic effect on fetal pulmonary vascular remodeling. This rat model induced by combined treatments can mimic human persistent pulmonary hypertension of the newborn.

Clinical significance of plasma N-terminal pro- B-type natriuretic peptide in respiratory distress syndrome of the preterm neonate

Plasma brain-type natriuretic peptide (BNP) is secreted by cardiac myocytes in response to pressure or volume overload. Recently, an assay to measure the N-terminal segment of the pro-hormone (NT-pro-BNP) was developed. (1) To determine the plasma levels of NT-pro-BNP in premature neonates without congenital heart disease; (2) to determine the relationship between the severity of respiratory distress syndrome (RDS) and plasma levels of NT-pro-BNP. Plasma levels of NT-pro-BNP were measured in premature neonates (<34 wks gestation) at 24 hours, and days 7 and 21 of life. Levels of NT-pro-BNP were compared between neonates with and without RDS. 45 neonates, 25/20 (F/M), gestational age 30 (25-33) weeks, birthweight 1290 (500-2220) g. RDS occurred in 21 (47%) neonates: RDS I (mild) = 7; RDS II (moderate) = 10; RDS III (severe) = 4. Comparative analysis revealed a significant increase in plasma level of NT pro-BNP at 24 hours (p = 0,001) and day 7 (p = 0,015) of life in patients with RDS. Plasmatic levels of NT-pro-BNP at 24 hours of age were significantly increased in patients with severe RDS than in patients with mild (p < 0,001) or moderate RDS (p < 0,002), after adjustment for gestational age and birthweight. plasma levels of NT-pro-BNP are directly related to increasing severity of RDS in neonates, suggesting a close relation to the functional impairment of pulmonary haemodynamical changes.

Brain‐type natriuretic peptide at birth reflects foetal maturation and antenatal stress

Antenatal stress, maturation and other foetal conditions affect the postnatal cardiovascular function. Atrial- (ANP) and brain-type natriuretic peptide (BNP) play important roles in regulating extracellular fluid volume and blood pressure, which may surrogate the foetal cardiovascular condition. The aim of this study was to investigate the dependence of serum ANP and BNP at birth on antenatal variables in high-risk infants. Plasma ANP and BNP levels in the umbilical cord blood were compared with antenatal clinical information in 280 infants. High levels of ANP and BNP were associated with multiple pregnancy, antenatal magnesium sulphate and foetal distress. Caesarean section (CS) was paradoxically associated with low ANP and high BNP; low ANP was related with CS before labour whereas high BNP was related with CS after the commencement of labour. High BNP levels further correlated with younger gestational age and intrauteral growth restriction. With regard to short-term postnatal variables, high BNP levels were associated with low Apgar scores and respiratory failure whereas high ANP only correlated with the latter. High natriuretic peptide levels were associated with prematurity at birth, uteral contraction and antenatal stress: cord blood ANP and BNP may be a useful surrogate marker for hidden antenatal stress.

Elevated CK‐MB mass and plasma brain‐type natriuretic peptide concentrations following convulsive seizures in children and adolescents: Possible evidence of subtle cardiac dysfunction

To evaluate the presence of myocardial injury during convulsive seizures in children and adolescents by determining serum concentrations of cardiac troponin I (cTnI), creatine kinase-MB mass (CK-MB mass), and plasma brain-type natriuretic peptide (BNP). Thirty-one children (20 boys; mean age, 6.6 +/- 5.34 years) with convulsive seizures and 50 healthy children were enrolled. Serum cTnI, CK-MB mass, and plasma BNP concentrations were analyzed 12 h after the seizure and repeated 7 days thereafter in the patient group and obtained one time in the control group. The difference between serum concentrations of cTnI obtained 12 h and 7 days after the seizure was not statistically significant. cTnI levels 12 h postictal and those in control subjects also were not significantly different. CK-MB mass and BNP at the 12th h were higher than those obtained on the 7th day (p < 0.05 and p < 0.001, respectively). Children with seizures had increased levels of CK-MB mass and BNP 12 h after seizure than control subjects (p < 0.05 and p < 0.001, respectively). The results of electrocardiography (ECG) recordings, which were obtained up to 30 min after seizure activity, were completely normal in patients with seizure. Normal cTnI levels are not indicative of overt myocardial necrosis in patients with seizures. However, markedly elevated BNP concentrations together with elevated CK-MB mass levels do suggest subtle cardiac dysfunction in patients with seizure, and further large-scale studies are warranted.

2-Dimensional Strain echocardiography and early detection of myocardial ischemia

Echocardiographic strain with strain rate imaging is a new technology enabling more reliable and comprehensive assessment of myocardial function. The spectrum of potential clinical applications is very wide due to its ability to differentiate between active and passive movement of myocardial segments, to quantify intraventricular dyssynchrony and to evaluate components of myocardial function, such as longitudinal myocardial shortening, that are not visually assessable. In-vivo and in-vitro validation of 2D-strain imaging technique have been undertaken and reached a point where it is considered ready for more widespread investigations into clinical utility, e.g. regarding myocarditis, arrhythmogenic right ventricular dysplasia/cardiomyopathy and regional ischemia. Moreover, longitudinal LV strain is closely related to log plasma brain-type natriuretic peptide levels in patients with congestive heart failure, both in patients with systolic and diastolic heart failure. We present a case of detection of coronary artery disease in a 55-year-old Italian man. This case focuses attention on the higher sensibility of the 2-Dimensional Strain echocardiography the diagnosis of myocardial ischemia in patients with coronary artery disease.

Clinical Summaries

Clinical Summaries

Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension

Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression. We recruited 41 patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects. Flow cytometry and in vitro assays were used to quantify EPCs and to assess cell function. The number of circulating CD34+, CD34+/AC133+, CD34+/KDR+, and CD34+/AC133+/KDR+ progenitor cells was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with New York Heart Association functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. The capacity of cultured peripheral blood mononuclear cells to form colonies and incorporate into tube-like structures was impaired in Eisenmenger patients. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies. Circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term.

Factors Associated with Incident Ischemic Stroke in Hospitalized Heart Failure Patients: A Pilot Study

Stroke is sometimes seen in patients with congestive heart failure (CHF). The factors that best predict incident stroke in hospitalized CHF patients are not well known. We performed this pilot study to explore the clinical markers of incident stroke in CHF patients. We studied 111 hospitalized patients with CHF (mean age, 67+/-11 years). Ambulatory blood pressure (BP) monitoring, blood tests, and echocardiography were performed in these patients just before they left the hospital, and all cardiovascular events during the study period were followed for an average of 18+/-9 months. Cox regression analysis was performed to explore the predictors of incident stroke using age, sex, body mass index (BMI), casual and ambulatory systolic BP (SBP), and brain-type natriuretic peptide (BNP). There were 10 stroke events (9%) during the follow-up period. The stroke group had higher nocturnal SBP and plasma BNP levels than the non-stroke group. With Cox regression analysis, both nocturnal SBP and BNP were significant predictors of incident stroke independent of other covariates. When nocturnal BP of 120 mmHg and BNP of 600 pg/mL (75th percentile) were used as cutoffs, nocturnal SBP > or =120 mmHg was associated with a 7-fold increase in the risk of incident stroke, while BNP > or =600 pg/mL was associated with a 46.6-fold increase. However, abnormal circadian BP patterns were not associated with incident stroke. In this pilot study, elevated nocturnal BP and high plasma BNP just before patients left the hospital were significant predictors of stroke events in CHF patients. Further study is needed to confirm this hypothesis.

Relationship of plasma brain-type natriuretic peptide levels to left ventricular longitudinal function in patients with congestive heart failure assessed by strain Doppler imaging

Background Plasma brain-type natriuretic peptide (BNP) levels have been used to diagnose congestive heart failure (CHF), but significant heterogeneity in BNP levels is not explained by standard echocardiographic indexes of cardiac function. Recent data indicate that longitudinal left ventricular (LV) dysfunction exists in the presence of normal standard echocardiographic indexes and BNP was predicted well by LV longitudinal systolic velocity. We examined whether longitudinal LV function assessed by strain or strain rate (SR) tissue Doppler imaging could be determinants of plasma BNP levels in patients with CHF. Methods We examined 137 consecutive patients with suspected CHF. Standard echocardiography and Doppler flow records were obtained. Strain, and SR at the basal and mid parts of the ventricle were investigated in 2 apical views. Tissue velocities of mitral annulus were also obtained. Plasma BNP levels were measured on the day of echocardiography. Results Multivariate analysis showed the mean longitudinal LV strain ( r = 0.75, P < 0.0001) to be an independent powerful predictor of plasma log BNP levels. Subgroup analysis (ejection fraction < 50%, n = 30; ejection fraction > 50%, n = 107) also showed that the mean longitudinal LV strain ( r = 0.89, P < 0.0001; r = 0.68, P < 0.0001, respectively) was only an independent predictor of log BNP levels. Conclusion Longitudinal LV strain is closely related to log BNP levels in patients with CHF, both in patients with systolic and diastolic heart failure.

Usefulness of Plasma Brain-Type Natriuretic Peptide Level to Differentiate Left Ventricular Diastolic Dysfunction from Preserved Diastolic Function in Patients With Systolic Dysfunction

The extent of left ventricular (LV) diastolic dysfunction is related to the finding that some patients with cardiomegaly due to LV systolic dysfunction have good exercise tolerance, although others have limited tolerance. A brain-type natriuretic peptide level of >/=104 pg/ml reliably enables the detection of relatively worse LV diastolic function in patients with systolic dysfunction, and this value may provide clinically useful information for the management of patients with cardiomegaly.

BNP for Diagnosing Restrictive Cardiomyopathy

Distinguishing between restrictive cardiomyopathy and constrictive pericarditis can be difficult using only physical examination, hemodynamic measurements, and noninvasive imaging. Given that brain-type natriuretic peptide (BNP) is released in response to myocardial stretch, researchers hypothesized that plasma BNP levels would be lower in patients with …