Elevated Brain Natriuretic Peptide Levels Research Articles

Abstract 5125: Elevated Serum Brain Natriuretic Peptide Level Predicts the Presence of the Left Atrial Appendage Dysfunction in Patients With Acute Ischemic Stroke

Background: It is well known that the left atrial appendage (LAA) dysfunction plays an important role in the occurrence of the cardioembolic stroke. It has been reported that the atrium is the main source of brain natriuretic peptide (BNP) in atrial fibrillation patients without heart failure. Therefore, we hypothesized that serum BNP levels are sensitive predictor for LAA dysfunction and thrombus formation in patients with acute ischemic stroke. Methods: We performed trans-thoracic and esophageal echocardiography within 7 days after the onset (male, n=64, 69±11 years old; female, n=38, 68±15 years old) and measured serum hemostatic markers and BNP in 103 patients with ischemic stroke. No patients had history of heart failure. Results: LAA thrombus was detected in 8 patients (36%) among 22 patients with atrial fibrillation. Even in 3 patients (4%) among 80 patients with sinus rhythm, LAA thrombus was detected. There were no significant differences in left ventricular end-diastolic dimension (LVDd), and the ratio of the early diastolic trans-mitral inflow velocity (E) to mitral annular velocity (E′) between patients with and without LAA thrombus (LVDd, 49±6 vs. 47±5 mm; E/E′, 8.6±1.3 vs. 7.2±0.9). Serum BNP levels were markedly higher in patients with LAA thrombus formation than in those without it (191 (128 –278) vs. 39 (13–100) pg/ml, P<0.01). Furthermore, in patients with sinus rhythm (n=80), the BNP levels were significantly correlated with LAA peak emptying flow velocity (R=−0.34, P<0.01). The multivariate logistic regression analysis revealed that BNP >120 was an independent predictor of LAA thrombus formation (odds ratio, 13.50; 95% confidence interval, 2.482–73.40; P=0.0026). Conclusions: The BNP levels were correlated with LAA peak emptying flow velocity. The elevated BNP level could be used as a non-invasive surrogate maker to predict LAA dysfunction and thrombus formation in patients with acute ischemic stroke.

Abstract 4852: High Resting Velocity in Intramyocardial Coronary Artery is Related to Elevated Plasma Brain Natriuretic Peptide Levels in Patients With Hypertension

Narrowings in intramyocardial coronary arteries (IMCA) and elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in hypertensive heart disease. To clarify the relation between abnormalities in IMCA and plasma BNP levels, 228 consecutive patients with hypertension were studied using high-frequency transthoracic Doppler echocardiography. We defined IMCA flow as abnormal one if acceleration flow in IMCA, indicating the presence of vessel narrowing, was detected by color flow mapping and the pulsed Doppler study demonstrated higher peak diastolic flow velocity than 32cm/sec (i.e. normal value + 2SD) in the site. Such abnormal flow in IMCA was demonstrated in 59 (56%) of 102 hypertensive patients with left ventricular hypertrophy (LVH) and in 36 (24%) of the other 126 hypertensive patients without LVH. Independent of LVH, the 95 hypertensive patients with abnormal IMCA flow had higher peak diastolic velocities in the IMCA (47.9±16.5 cm/s vs. 24.3±5.4 cm/s, p<0.01) and more elevated plasma BNP levels (131.0±24.4 pg/ml vs. 45.8±5.7 pg/ml, p<0.01) than those without abnormal IMCA flow. Furthermore, peak diastolic velocities had a significant correlation with log BNP values (p<0.01). The index of % area stenosis (IAS) estimated by the continuity equation was 46±14% at the site of acceleration flow, indicating the presence of mild to moderate lumen narrowing in the IMCA. The patients with the IAS of 50% and over had significantly higher log BNP values as compared to those with the IAS of less than 50% (p<0.05), indicating plasma BNP levels may be elevated by factors associated with lumen narrowing in the IMCA. Conclusions: High resting velocity in IMCA is at least partly related to elevated BNP levels in patients with hypertension independent of LVH.

Is a Pre-Operative Brain Natriuretic Peptide or N-Terminal Pro–B-Type Natriuretic Peptide Measurement an Independent Predictor of Adverse Cardiovascular Outcomes Within 30 Days of Noncardiac Surgery?: A Systematic Review and Meta-Analysis of Observational Studies

We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro-B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery. Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting. We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model. Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I(2) = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I(2) = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I(2) = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I(2) = 62.2%); the p value for interaction was 0.28. These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.

Prognostic Value of Brain Natriuretic Peptide in Noncardiac Surgery

The prognostic role of brain natriuretic peptide (BNP) measurement before noncardiac surgery is unclear. The authors therefore performed a meta-analysis of studies in patients undergoing noncardiac surgery to assess the prognostic value of elevated BNP or N-terminal pro-BNP (NT-proBNP) levels in predicting mortality and major adverse cardiovascular events (MACE) (cardiac death or nonfatal myocardial infarction). Unrestricted searches of MEDLINE and EMBASE bibliographic databases were performed using the terms "brain natriuretic peptide," "b-type natriuretic peptide," "BNP," "NT-proBNP," and "surgery." In addition, review articles, bibliographies, and abstracts of scientific meetings were manually searched. The meta-analysis included prospective studies that reported on the association of BNP or NT-proBNP and postoperative major adverse cardiovascular event (MACE) or mortality. The study endpoints were MACE, all-cause mortality, and cardiac mortality at short-term (less than 43 days after surgery) and longer-term (more than 6 months) follow-up. A random-effects model was used to pool study results; funnel-plot inspection was done to evaluate publication bias; Cochrane chi-square test and I testing was used to test for heterogeneity. Data from 15 publications (4,856 patients) were included in the analysis. Preoperative BNP elevation was associated with an increased risk of short-term MACE (OR 19.77; 95% confidence interval [CI] 13.18-29.65; P < 0.0001), all-cause mortality (OR 9.28; 95% CI 3.51-24.56; P < 0.0001), and cardiac death (OR 23.88; 95% CI 9.43-60.43; P < 0.00001). Results were consistent for both BNP and NT-proBNP. Preoperative BNP elevation was also associated with an increased risk of long-term MACE (OR 17.70; 95% CI 3.11-100.80; P < 0.0001) and all-cause mortality (OR 4.77; 95% CI 2.99-7.46; P < 0.00001). Elevated BNP and NT-proBNP levels identify patients undergoing major noncardiac surgery at high risk of cardiac mortality, all-cause mortality, and MACE.

THIS MONTH IN Anesthesiology

Etomidate, has limited clinical utility due to suppression of adrenocortical steroid synthesis. The first etomidate analogue, (R)-3-methoxy-3-oxopropyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), was designed to be susceptible to ultra-rapid metabolism to reduce this effect. MOC-etomidate potently enhanced γ-aminobutyric acid type A receptor function and demonstrated first-order metabolism in human liver homogenates with an in vitro half-life of 4.4 min compared with &gt; 40 min for etomidate. A rapid, brief loss of righting reflex and minimal hemodynamic changes were observed in rats without adrenocortical suppression MOC-etomidate, is rapidly metabolized, ultra–short-acting, and does not produce prolonged adrenocortical suppression and maintains the favorable pharmacologic properties of etomidate. See the accompanying Editorial View on page 229 Blood transfusion may have an adverse effect on long-term health. A prospective observational study assessed long-term survival in patients undergoing coronary artery surgery who received a perioperative allogeneic blood transfusion. Health outcomes of 1,841 consecutive patients with isolated nonemergency first-time coronary artery surgery and survival &gt; 60 days after surgery were determined. Of the 1,062 patients transfused, 266 died (mean follow-up of 8.1 yr). A new malignant condition was recorded on the death certificate of 27% of patients who were transfused, compared with 43% who were not. Transfusion of blood products was not associated with long-term survival. Patients undergoing coronary artery surgery who have received moderate amounts of blood (≤ 6 units) should be reassured that they are unlikely to experience a reduction in long-term survival.To assess the prognostic value of elevated brain natriuretic peptide (BNP) or N -terminal pro-brain natriuretic peptide (NT-proBNP) levels in predicting mortality and major adverse cardiovascular events (MACE), a meta-analysis was performed of studies in patients undergoing noncardiac surgery using unrestricted MEDLINE and EMBASE searches. Preoperative BNP elevation was significantly associated with an increased risk of short-term MACE (&lt; 43 days postsurgery), all cause mortality, and cardiac death. Elevated NT-proBNP levels were also predictive. Preoperative BNP elevation was also significantly associated with an increased risk of long-term MACE (&gt; 6 months) and all cause mortality. These data suggest that elevated BNP and NT-proBNP levels may identify patients undergoing major noncardiac surgery at high risk of cardiac events.Growing evidence suggests that microvascular dysfunction is the key element of the pathogenesis of septic shock. This retrospective study assessed the outcome and muscle tissue oxygenation (Sto2) of septic shock patients after early resuscitation using early goal-directed therapy. Sto2was monitored in septic shock patients using a tissue spectrometer. No difference was observed between groups with the exception of pulse oximetry saturation (Spo2; 94% vs. 97%, P = 0.04). The Sto2values were significantly lower in nonsurvivors than in survivors (73% vs. 84%, P = 0.02). Further investigations are required to determine if correction of an impaired level of Sto2improves patient outcomes.Clonidine added to intermediate or long-acting local anesthetics for single-shot nerve blocks prolongs duration by about 2 h. Side effects may limit its usefulness.A process-dissociation procedure, which corrected for guessing, was used to determine if more accurate results of auditory memory could be obtained.The perioperative implications of adults with congenital heart disease undergoing noncardiac surgery are reviewed.Intravenous infusion tests have limited utility for predicting analgesia in chronic pain patients.

Application of Classic Heart Failure Definitions of Asymptomatic and Symptomatic Ventricular Dysfunction and Heart Failure Symptoms With Preserved Ejection Fraction to Patients With Systemic Right Ventricles

Heart failure guidelines classify patients into subgroups with asymptomatic versus symptomatic ventricular dysfunction versus heart failure with a preserved ejection fraction. In this study, this approach was applied in a series of patients with complete transposition of the great arteries after atrial switch to assess to what extent this classification fits patients with systemic right ventricles. The study included stable adult patients after atrial switch, stratified according to preserved versus impaired systolic function (fractional area change > or =0.40 vs <0.40), absence versus presence of symptoms, absence versus presence of significant tricuspid regurgitation (TR), and normal versus elevated brain natriuretic peptide (BNP) levels. Twenty-two of 42 participants (52.4%; mean age 18.2 +/- 2.8 years) had preserved systolic function, and 20 (47.6%) had impaired systolic function; 10 patients (23.8%) had asymptomatic right ventricular (RV) dysfunction. The latter more frequently had significant TR (p = 0.04) and elevated BNP levels (p = 0.008), compared with asymptomatic patients with preserved systolic function. Normal BNP levels independently predicted preserved RV function in all patients (odds ratio 6.4, 95% confidence interval 1.03 to 39.1, p = 0.04) and in asymptomatic patients (odds ratio 14.4, 95% confidence interval 1.2 to 176.2, p = 0.03). Heart failure symptoms with preserved systolic function were present in 5 patients (11.9%), including 3 patients with significant TR. In conclusion, asymptomatic RV dysfunction and heart failure symptoms with preserved systolic function are common in patients with systemic right ventricles. BNP levels can be used to predict preserved systolic RV function, especially in asymptomatic patients. Heart failure symptoms with preserved RV systolic function can be frequently explained by the coexistence of significant TR.

Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin's lymphoma (NHL) may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP) as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP), not exceeding the total allowed dose of doxorubicin (500 mg/m2). Ten healthy controls were included in our study. Human heart-type fatty acid-binding protein (H-FABP) was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF) of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

Correlation between BNP Levels and Doppler Echocardiographic Parameters of Left Ventricle Filling Pressure in Patients with Chagasic Cardiomyopathy

Cardiomyopathy is the most important manifestation of Chagas' disease. Brain natriuretic peptide (BNP) level and Doppler echocardiographic parameters for diastolic dysfunction have shown correlation with left ventricle (LV) filling pressures. The purpose of this study is to compare BNP levels with Doppler echocardiographic parameters in patients with chagasic cardiomyopathy. Forty-three patients (69.8% men; mean age 41.0 +/- 10.4 years) were submitted to an echocardiographic study and 39 had their BNP levels measured. BNP levels increased with the deterioration of the diastolic function (P=0.025). Pulmonary venous flow parameters were correlated with BNP levels, but E/E'ratio (E'measured at the inferior mitral annulus) was the only diastolic parameter that remained an independent predictor of elevated BNP levels in the multivariate analysis. The area under the receiver-operating curve for BNP to detect E/E' >15 was 0.875. A BNP value of 280.4 pg/ml had a sensitivity of 96% and a specificity of 75% for predicting E/E' >15. In a group of patients with chagasic cardiomyopathy, BNP levels correlated with diastolic function patterns regardless of systolic function. The E/E'ratio (inferior wall) was the only isolated parameter of diastolic function that was independently associated with BNP levels.

Echocardiography and brain natriuretic peptide as prognostic indicators in idiopathic pulmonary fibrosis

Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) is associated with poor prognosis. Recently echocardiography and brain natriuretic peptide (BNP) have been used as non-invasive markers for PH suggesting that they may also be used as markers for survival. The aim of this study was to evaluate the clinical usefulness of echocardiography and BNP by analyzing their association with survival. Retrospective review of 131 patients with IPF who underwent both echocardiography and BNP measurement at a tertiary referral center. Mean follow-up period was 10.1 months. Using systolic pulmonary arterial pressure of 40 mmHg as a threshold for PH, patients with PH had poor survival (1-year mortality rate: 61.2%, mean survival: 10.8 months) than those without PH (19.9%, 23.7 months; p<0.001). The prognosis of the subjects with increased BNP levels was poorer than those with normal BNP levels (1-year mortality rate: 70.5% vs. 23.7%, mean survival: 11.0 months vs. 22.5 months; p<0.001) and on multivariate analysis, only BNP level was an independent predictor of prognosis. On serial evaluation, the survival of patients with newly developed PH and/or elevated BNP levels was similar to that of patients with PH at the initial measurement, suggesting that development of PH is indicative of poor prognosis regardless of the timing of the test. Although both BNP level and PH by echocardiography are clinically useful non-invasive and easily repeatable markers of prognosis, BNP level seems to be better.

Changes of BNP Level and Pulmonary Arterial Pressure during An Acute Sickle Cell Crisis, Comparison with Steady State

Background: The heart is frequently involved in Sickle Cell Anemia (SCA). Cardiomegaly is a usual finding, significant arrythmias and sudden death are common, and 30% of patients with both homozygous and heterozygous SCA develop Pulmonary Arterial Hypertension (PAH), a major risk factor for higher mortality in this population. Brain Natriuretic Peptide (BNP) and echocardiographic data could provide important prognostic and diagnostic information about PAH in SCD. High levels of BNP, which is released from ventricular cardiomyocytes in response to their stretch, reflect cardiac chamber volume and pressure overload in various conditions. In patients with PAH, BNP levels correlate with the severity of Pulmonary Artery Pressure (PAP) elevation and right ventricular dysfunction. In human, the half life of BNP is 20 minutes, reflecting the fluctuation of BNP levels during different stages of any acute cardiac pathology.Methodology: The hypothesis of this prospective IRB approved study was to investigate the BNP level and PAP elevation during an acute Sickle Cell Crisis (SCC), in particular in those with intrathoracic structures involvement. Between December 2006 and July 2008, 81 patients were registered after a written informed consent was obtained. We collected the BNP levels and echocardiographic data of patients with SCD and compared them in two group; those who were admitted with Sickle Cell Crisis (SCC) and those who returned to clinic in Steady State (SS) for follow up. The data were obtained on the first day of admission in SCC group. The primary endpoint was the elevation of the BNP level and the secondary endpoint was elevation of the PAP during a SCC, which were compared with SS patients. The inclusion criterion was age above 18 and having one of the sickle cell syndromes, requiring hospital admission.Results: Forty nine patients (59%) were female, and 34 (41%) patients were male. Their ages ranged from 19 to 65, mean (SD) 30.2 (9.7) years. The mean (SD) levels of BNP were significantly higher in patients who were admitted with one of the acute complications or vaso-occlusive crisis of sickle cell, [177.3 (23.4) pg/ml], when compared with its levels in SS, [34.17 (6.1) pg/ml], (95% CI 61.4 to 225.0, p<.001) (Figure 1). An elevated BNP level was defined as levels more than 100 pg/ml. A further subgroup analysis revealed that the BNP levels were even more significantly higher in patients with acute chest syndrome or other intrathoracic events [(n= 17, mean (SD) 363.6 (121.3) pg/ml], when compared with those of simple acute sickle cell crisis, [(n= 35, mean (SD) 167.7 (26.8) pg/ml] (p=.038) (Figure 1). Topographic data about heart chambers' sizes, volumes, and pressures were obtained by Echocardiography and compared in two groups. While only 23.1% of patients in SS group had elevated PAP with a mean (SD) of 43 (2.1) mmHg, 41.1% (n=21) of patients with SCC had elevated PAP with mean (SD) 45.9 (2.1) mmHg, with no significant difference between two groups with PAH (p=.608).Conclusion: Patients with either homozygous or heterozygous forms of SCA can have cardiac complications, such systolic and diastolic dysfunction. Hypoxemia leads to raised levels of BNP production. In patients with SCA, an elevated BNP level largely reflects the severity of right ventricular dysfunction associated with PAH. Our data revealed that BNP level and PAP are increased during vaso-occlusive crisis of SCA, in particular during those life-threatening complications, such acute chest syndrome. These changes seem to be temporary and with clinical improvement, the majority of patients' BNP levels and PAP return to the baseline, although some will never normalize. [Display omitted]

Preoperative plasma brain natriuretic peptide level is an independent predictor of postoperative atrial fibrillation following off-pump coronary artery bypass surgery

Atrial fibrillation (AF) is a frequent complication after coronary artery bypass surgery. Postoperative AF can lead to thromboembolic events, prolonged hospital stay, and increased costs. Recent reports have shown that an elevated plasma brain natriuretic peptide (BNP) level is associated with AF. The purpose of this prospective study was to test the hypothesis that preoperative BNP level is a predictor of postoperative AF following off-pump coronary artery bypass surgery (OPCAB). One hundred and fifty patients without a history of AF undergoing elective isolated OPCAB were enrolled. Plasma BNP level was measured preoperatively. Heart rate and rhythm were continuously monitored during the first 72 h after surgery. Twenty-six patients (17.3%) exhibited postoperative AF. This proportion is similar to those reported in earlier studies. Univariate analysis demonstrated that age (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.008 to 1.114; P = 0.023), previous myocardial infarction (MI; OR, 2.628; 95% CI, 1.031 to 6.697; P = 0.043), and BNP level (OR, 7.336; 95% CI, 2.401 to 22.409 / log BNP level; P < 0.001) were accurate predictors of postoperative AF. Stepwise multivariate regression analysis indicated age (OR, 1.059; 95% CI, 1.002 to 1.120; P = 0.043) and BNP level (OR, 6.272; 95% CI, 1.980 to 19.861/log BNP level; P = 0.002) as the only independent predictors of postoperative AF. Preoperative BNP level is an independent predictor of postoperative AF following OPCAB. Our findings permit us to stratify the risk of AF and to plan prophylactic strategies in high-risk patients.

Symptomatic ventricular tachyarrhythmia is associated with delayed gadolinium enhancement in cardiac magnetic resonance imaging and with elevated plasma brain natriuretic peptide level in hypertrophic cardiomyopathy

Delayed gadolinium enhancement (DGE) in cardiac magnetic resonance (CMR) imaging indicates the areas with myocardial fibrosis, which are suggested to be arrhythmogenic substrate in hypertrophic cardiomyopathy (HCM). Elevated brain natriuretic peptide (BNP) is associated with cardiovascular events in HCM. We investigated the grade of DGE in CMR and plasma BNP levels in HCM patients with or without symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF). We recruited 26 consecutive untreated HCM patients without any symptoms of heart failure. They were divided into 2 groups: (1) patients with symptomatic VT/VF [VT/VF(+) group, n=6]; (2) patients without symptomatic VT/VF [VT/VF(-) group, n=20]. CMR was performed to evaluate left ventricular geometry and the grade of DGE. Plasma BNP levels, left ventricular mass index, and the number of segments with positive DGE were greater in the VT/VF(+) group than in the VT/VF(-) group (698.1+/-387.6 vs. 226.9+/-256.8 pg/ml, p=0.006; 152.3+/-49.5 vs. 89.5+/-24.1 g/m(2), p=0.003; 9.7+/-5.7 vs. 3.5+/-3.3, p=0.013). On logistic regression, adjusted odds ratio for symptomatic VT/VF was 214 for logBNP (95% confidence interval [CI] 1.2-37,043, p=0.04) and 1.54 for DGE score (95% CI 1.01-2.34, p=0.04). High plasma BNP levels and the enlarged area of DGE in CMR were associated with symptomatic ventricular tachyarrhythmia. These factors may be useful markers for detecting high-risk patients of sudden cardiac death in HCM.

Relationship of sustained brain natriuretic peptide release after reperfused acute myocardial infarction with gated SPECT infarct measurements and its connection with collagen turnover and left ventricular remodeling

The relationship among plasma brain natriuretic peptide (BNP), markers of extracellular matrix (ECM) remodeling, and left ventricular (LV) dilation after reperfused acute myocardial infarction is poorly known. Echocardiogram, plasma BNP, and ECM degradation markers (serum amino-terminal telopeptide of type I procollagen and type III procollagen and carboxy-terminal telopeptide of type I procollagen [ICTP]) were evaluated in 34 patients at days 1, 3, and 30 after first reperfused acute myocardial infarction. At 1 month, infarct size and severity and LV volume were measured by sestamibi gated single photon emission computed tomography. Patients were stratified according to day 3 BNP levels into 2 groups: group 1 (n = 17) had BNP values over the median value, and group 2 (n = 17) had BNP values under the median value. Infarct size and severity were similar in the 2 groups. LV volumes increased in group 1 but decreased in group 2 (P < .01). BNP values, LV volume/mass index, and infarct size were independent predictors of 1-month LV dilation (beta = .58 [P = .001], beta = .41 [P = .01], and beta = .32 [P = .03], respectively). Levels of serum amino-terminal propeptide of type I procollagen and type III procollagen were similar in both groups. The level of ICTP increased significantly in group 1 only, and after 3 days, it was higher (P < .01) than in group 2. In group 1 ICTP significantly interacted with the relationship between BNP release and serial changes in LV volumes (F = 4.87, P = .03). ICTP is related to elevated BNP level independently of infarct size and severity and interacts with the relationship between BNP and LV dilation. BNP levels could play a role in LV remodeling by favoring ECM degradation.

Diagnostic and prognostic impact of brain natriuretic peptide in cardiac and noncardiac diseases

Cardiac secretion of brain natriuretic peptide (BNP) increases with the progression of congestive heart failure (CHF). The plasma measurement of BNP emerged recently as a useful, cost-effective biomarker for the diagnosis and prognosis of CHF. BNP assay is useful for evaluating patients with acute dyspnea, because a low level can help rule out CHF in primary care settings and reduce the demand for echocardiography. Equally, BNP level can be particularly useful in recognizing heart failure in a patient with acute dyspnea and a history of chronic obstructive pulmonary disease. However, although the clinical use of BNP as a biomarker in CHF is increasing, the specificity of BNP in CHF is not strong, suggesting that other mechanisms beyond simple ventricular stretch stimulate BNP release. Multiple disorders in the intensive care unit, apart from CHF, cause elevated BNP levels, including cardiovascular disease states such as ischemia, arrhythmias, cardiac hypertrophy, and coronary endothelial dysfunction, as well as disorders of no cardiac origin, such as sepsis, septic shock, and acute respiratory distress syndrome. Moreover, the impact of increased BNP in patients with sepsis is not clear. The relationship between BNP and both left ventricular ejection fraction and left-sided filling pressures is weak, and data on the prognostic impact of high BNP levels in patients with sepsis are conflicting. Nevertheless, this review highlights the potential benefits of BNP in the recognition and management of heart failure, and defines the gray zones of BNP levels; it also identifies conditions influencing BNP levels in relation to a certain heart failure and describes conditions of no cardiac origin with increased BNP.

Increased Morning Brain Natriuretic Peptide Levels in Children With Nocturnal Enuresis and Sleep- Disordered Breathing: A Community-Based Study

Habitual snoring and obstructive sleep apnea have been associated with bed-wetting in children, and effective obstructive sleep apnea treatment may improve enuresis. The purpose of this work was to assess whether habitual snoring is associated with increased incidence of enuresis and whether severity of obstructive sleep apnea correlates with enuretic frequency and to evaluate brain natriuretic peptide levels. Parental surveys of 5- to 7-year-old children were reviewed for habitual snoring and enuresis. Enuresis was also assessed in a cohort of 378 children with habitual snoring undergoing overnight polysomnographic evaluation, and brain natriuretic peptide plasma levels were determined in 20 children with obstructive sleep apnea, 20 with habitual snoring without obstructive sleep apnea, and 20 nonsnoring children, matched for enuresis. There were 17,646 surveys completed (50.6% boys; 18.3% black). A total of 1976 (11.2%) of these children were habitual snoring (53% boys; 25.2% black). A total of 531 habitual snoring children also had enuresis (26.9%), with a predominant representation of boys (472 boys [87.5%]). Among the 15670 nonsnoring children, enuresis was reported in 1821 children (11.6%), of whom 88.8% were boys. However, enuresis among 378 children with habitual snoring did not correlate with the magnitude of sleep respiratory disturbances. Indeed, enuresis was reported in 33 of 149 children with obstructive sleep apnea (obstructive apnea hypopnea index: >2 per hour of total sleep time; 53% boys) as compared with 36 habitual snoring children with enuresis (62% boys) and obstructive apnea hypopnea index <2 per hour of total sleep time. Brain natriuretic peptide levels were elevated among children with enuresis and were marginally increased among children with obstructive sleep apnea. Habitual snoring is associated with increased prevalence of enuresis, and brain natriuretic peptide levels are increased in enuretic children with further increases with obstructive sleep apnea. However, the prevalence of enuresis is not modified by severity of sleep disturbance. Even mild increases in sleep pressure because of habitual snoring may raise the arousal threshold and promote enuresis, particularly among prone children, that is, those with elevated brain natriuretic peptide levels.

Cerebral salt wasting and elevated brain natriuretic peptide levels after traumatic brain injury: 2 case reports

Background Historically, hyponatremia in patients with varying brain diseases was termed cerebral salt wasting. Hyponatremia secondary to CSW was reported to be a distinct entity from SIADH, with the distinguishing feature of decreased extracellular fluid volume. Brain natriuretic peptide, a peptide with natriuretic, vasorelaxant, and aldosterone-inhibiting properties, was recently implicated in aneurysmal SAH patients with CSW. Here, we describe 2 cases of CSW in TBI patients with elevated BNP levels. This phenomenon has not been previously described. Case Description Two patients with TBI and hyponatremia were subject to analysis. Central lines were placed to assess volume status. Levels of BNP were measured at the onset of hypertonic saline infusion. Electrocardiogram and cardiac enzyme studies were performed to assess cardiac function. Serial imaging was performed to assess the extent of brain injury. Conclusions These patients with TBI had findings consistent with CSW with elevated BNP levels in the setting of normal cardiac function. In both cases, a high BNP level was observed after declining plasma Na levels despite aggressive hypertonic saline infusion. High BNP levels may be associated with CSW. Further studies are necessary to establish a causative role for BNP in TBI-induced CSW.

Response to Letter Regarding Article, “Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure: The Importance of Change Over Time”

HomeCirculationVol. 117, No. 4Response to Letter Regarding Article, “Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure: The Importance of Change Over Time” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter Regarding Article, “Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure: The Importance of Change Over Time” Wayne L. Miller, MD, PhD, Karen A. Hartman, BSN, CCRC, Diane E. Grill, MSc, Mary F. Burritt, PhD, Richard J. Rodeheffer, MD, John C. BurnettJr, MD and Allan S. Jaffe, MD Wayne L. MillerWayne L. Miller Mayo Clinic, Rochester, Minn Search for more papers by this author , Karen A. HartmanKaren A. Hartman Mayo Clinic, Rochester, Minn Search for more papers by this author , Diane E. GrillDiane E. Grill Mayo Clinic, Rochester, Minn Search for more papers by this author , Mary F. BurrittMary F. Burritt Mayo Clinic, Rochester, Minn Search for more papers by this author , Richard J. RodehefferRichard J. Rodeheffer Mayo Clinic, Rochester, Minn Search for more papers by this author , John C. BurnettJrJohn C. BurnettJr Mayo Clinic, Rochester, Minn Search for more papers by this author and Allan S. JaffeAllan S. Jaffe Mayo Clinic, Rochester, Minn Search for more papers by this author Originally published29 Jan 2008https://doi.org/10.1161/CIRCULATIONAHA.107.740936Circulation. 2008;117:e24We thank Drs Ballo, Bocelli, and Mondillo for their interest in our recent article.1 They raise an interesting issue relating to the finding in our study cohort that cardiac resynchronization therapy (CRT) was associated with adverse effects. They point out correctly that in several reports, CRT and brain natriuretic peptide (BNP) are associated with clinical benefit and that over time, as in our longitudinal study, a reduction in BNP levels occurs (CARE-HF).2 Thus, they express a concern that this known collinearity of BNP and CRT, albeit for different outcomes, could have confounded the multivariate model relating baseline risk factors to the outcome of death and cardiac transplantation in this patient cohort. This is a reasonable possibility to explore, as we have done.It is important to keep in mind the context of our findings and to appreciate that only 27 patients (14% of the study cohort) received CRT, making a more comprehensive analysis of this subset problematic. In addition, many of these patients received CRT early after its introduction, given the relatively long timeline of our study. Thus, some of these patients likely were those with more severe disease that characterized the patients selected at that time for this type of therapy. However, statistical confounding is also possible. To address the concern that a strong association between the independent variables of BNP elevation and CRT (collinearity) could have affected the resulting coefficient in the model (Table 3 in our article1), we re-analyzed the multivariate model without the CRT variable. If over-adjustment was present due to collinearity, it would be expected that the hazard ratio for an elevated BNP level would change significantly and likely become a more prominent predictive factor. However, re-analysis showed the hazard ratio for BNP to be 1.58 (P=0.114), which is only a minor change from the hazard ratio of 1.53 (P=0.146) with CRT included in the model. Accordingly, although the findings from this multivariate model of baseline risk factors are unexpected, given the present state of the art, they appear to be valid within the timelines and context of this patient cohort. Obviously in this study,1 as with all observational data, caution is needed in attributing causation to these correlations.DisclosuresDr Miller has received a research grant from Dade Behring. Dr Jaffe has received a research grant from Dade Behring and has served as a consultant to Roche Diagnostics and Dade Behring. The other authors report no conflicts. References 1 Miller WL, Hartman KA, Burritt MF, Grill DE, Rodeheffer RJ, Burnett JC Jr, Jaffe AS. Serial biomarker measurements in ambulatory patients with chronic heart failure: the importance of change over time. Circulation. 2007; 116: 249–257.LinkGoogle Scholar2 Cleland JGF, Daubert J-C, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005; 352: 1539–1549.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails January 29, 2008Vol 117, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.107.740936 Originally publishedJanuary 29, 2008 PDF download Advertisement SubjectsHeart Failure

Elevated Plasma Brain Natriuretic Peptide Levels Independent of Heart Disease in Acute Ischemic Stroke: Correlation with Stroke Severity

We tested the hypothesis that plasma brain natriuretic peptide (BNP) levels are elevated in patients with acute cerebrovascular diseases (CVD) independent of heart disease, and reflect CVD severity. After careful evaluations for heart disease, the study included 79 consecutive patients with CVD without any evidence of heart disease admitted within 48 h after onset (71+/-10 years), and 26 control subjects without CVD (CT, 67+/-12 years). Ischemic stroke subtypes were defined by the TOAST classification. Large-artery atherosclerosis (LAA, n=27), small-artery occlusion (SAO, n=27), and intracerebral hemorrhage (ICH, n=25) were included. The plasma BNP levels were measured at admission and 1 month later. Stroke severity and brain infarct volume were evaluated. There were no significant differences in the clinical profiles including echocardiographic parameters among the groups. The plasma BNP level (pg/mL) upon admission was higher in LAA (70.6+/-53.9) than in SAO (38.2+/-28.4) and CT (28.5+/-19.9) (both p<0.05). The level in ICH (47.3+/-28.6) was not significantly different from that in CT. The BNP level in ischemic stroke was positively correlated with the NIH Stroke Scale (NIHSS) (rho=0.42, p<0.05) and infarct volume (r=0.34, p<0.05). Brain infarct volume and NIHSS were independent contributors to the plasma BNP level in ischemic stroke. One month later, the BNP level was significantly decreased and was similar in all CVD groups. The plasma BNP level transiently increased in patients with LAA independently of heart disease, and reflected infarct volume and the severity of acute ischemic stroke.

Plasma Brain Natriuretic Peptide Level After Hybrid Therapy With Pulmonary Vein Isolation and Antiarrhythmic Drugs for Atrial Fibrillation

The atrial fibrillation (AF) recurrence rate after pulmonary vein isolation (PVI) has been relatively high and in some unsuccessful PVI cases, antiarrhythmic drugs that were ineffective before PVI may become effective (hybrid therapy). The purpose of this study was to investigate the relationship between the brain natriuretic peptide (BNP) level and the effect of the hybrid therapy. In 28 lone AF patients undergoing hybrid therapy, the plasma BNP level was measured before PVI and before and 3 months after administering an antiarrhythmic drug. Fifteen patients were free of AF after the hybrid therapy (effective group), and 13 still had recurrent AF after (noneffective group). At baseline, in all patients the BNP level was elevated, and there were no significant differences in the BNP level between the 2 groups. The BNP level was significantly decreased after PVI in the effective group (56.8 +/- 23.1 versus 37.5 +/- 16.7 pg/mL, P < 0.05) but not in the noneffective group (74.3 +/- 47.8 versus 79.7 +/- 54.4 pg/mL, NS). The elevated BNP level normalized in all effective group patients. The criterion consisting of a net value of < 60.0 pg/mL or a reduction in the BNP level of > 10.0 pg/mL after PVI predicted the effective group patients with a high accuracy. A significant reduction in the BNP level after PVI may be a useful predictor of the responders to antiarrhythmic drug therapy in patients with recurrent AF after PVI. The hybrid therapy may be effective in patients whose PVs serve as a dominant AF substrate.

Abstract 3742: Elevated Brain Natriuretic Peptide and C-reactive Protein Interactively Increased Cardiovascular and All-cause Mortality Risk in Hemodialysis Patients

Background: It has been established that elevated brain natriuretic peptide (BNP) and C-reactive protein (CRP) levels are increasingly associated with cardiovascular (CV) morbidity. We examined the prognostic usefulness of combining BNP and CRP for predicting CV mortality in hemodialysis (HD) patients. Methods: Plasma BNP and serum CRP were measured consecutively in 500 HD patients. These patients were divided into 4 groups according to plasma BNP levels; Quartile 1 (Q1): &lt; 45 ng/L, Q2: 145–266 ng/L, Q3: 267– 628 ng/L, and Q4: &gt;628 ng/L, and serum CRP levels; Q1: &lt;0.09 mg/dl, Q2: 0.09 – 0.27 mg/dl, Q3: 0.27–1.17mg/dl and Q4: &gt;1.17mg/dl, respectively. All patients were followed up for 8 years. Results: On Cox proportional hazards analysis, hazard ratio (HR) of elevated BNP levels was 3.93 (95%CI 2.06 –7.52 for Q4 vs Q1) for CV mortality and 3.51 (95%CI 2.18 –5.64 for Q4 vs Q1) for all-cause mortality, respectively (both p&lt;0.0001). Similarly, HR of elevated CRP levels was 6.00 (95%CI 2.89 –12.45) for CV mortality and 8.19 (95%CI 4.53–14.77) for all-cause mortality, respectively (both p&lt;0.0001). In the setting of combination of BNP and CRP, the risk of CV mortality was 23.6-fold in the highest quartile on both BNP and CRP compared with the lowest quartile on both BNP and CRP. Similarly, the risk of mortality was 45.3-fold (Figure ). These variables were significant after adjustment for other CV risk factors. Conclusions: Elevated BNP and CRP interactively increased CV and all-cause mortality risk in HD patients. The combination of BNP and CRP is useful for risk stratification in HD patients because the combination of these variables is more closely related to outcome than either variable alone.