Changes In NT-proBNP Research Articles

Post-discharge changes in NT-proBNP and quality of life after acute dyspnea hospitalization as predictors of one-year outcomes

Aims The association of serial NT-proBNP changes and poor quality of life (QOL) with progressive heart failure (HF) and clinical outcomes in emergency department dyspnea patients is poorly understood. Methods and results The predictive value of changes in NT-proBNP and QOL (Minnesota Living with Heart Failure scale) from baseline to 30-day follow-up was examined for all-cause 1-year mortality and HF hospitalization. Patients with an initially elevated NT-proBNP (≥ 300 ng/L) which persisted at 30-days (no ≥ 25% decrease) were at high risk of death or HF hospitalization (HR = 6.36, 95%CI = 3.04–13.28). Combined with sustained poor QOL, these subjects with persistently elevated NT-proBNP were at highest mortality risk or HF hospitalization (HR = 8.75, 95%CI = 3.62–21.16). Conclusions Dyspnea patients with elevated NT-proBNP concentrations and no improvement in either NT-proBNP or QOL at 30-days are at high risk of mortality and HF hospitalization. These data highlight the value of serial biomarker measurements combined with serial evaluations for QOL.

No effect of group-based aerobic interval training on N-terminal pro- B-type natriuretic peptide levels in patients with chronic heart failure

Objectives. Exercise training might improve cardiac function as well as functional capacity in patients with chronic heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT pro-BNP), is associated with the severity of the disease, and has been reported to be an independent predictor of outcome in CHF. We evaluated the effect of a four months group-based aerobic interval training program on circulating levels of NT pro-BNP in patients with CHF. We have previously reported improved functional capacity in 80 patients after exercise in this exercise program. Methods. Seventy-eight patients with stable CHF (21% women; 70±8 years; left ventricular ejection fraction 30±8.6%) on optimal medical treatment were randomized either to interval training (n=39), or to a control group (n=39). Circulating levels of NT pro-BNP, a six minute walk test (6MWT) and cycle ergometer test were evaluated at baseline, post exercise, and further after 12 months. Results. There were no significant differences in NT pro-BNP levels from baseline to either post exercise or long-term follow-up between or within the groups. Inverse correlations were observed between NT pro-BNP and 6MWT (r=−0.24, p=0.035) and cycle exercise time (r=−0.48, p<0.001) at baseline. But no significant correlations were observed between change in NT pro-BNP and change in functional capacity (6MWT; r=0.12, p=0.33, cycle exercise time; r=0.04, p=0.72). Conclusion. No significant changes in NT pro-BNP levels were observed after interval training, despite significant improvement of functional capacity.

Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial

Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin-angiotensin-aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo. AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function <or=40% but with an increased level of NP 3-10 days after admission to aliskiren, valsartan, their combination, and placebo. The primary endpoint was the change in NT-proBNP from baseline to Week 8. NT-proBNP declined significantly in each treatment arm, including placebo, by Week 8, though there were no differences in the reduction between treatment strategies (42% in placebo, 44% in aliskiren, 39% in valsartan, and 36% in combination arm). Although several subgroups had higher baseline levels of NP and greater reductions over the study period, there were no differences among treatment groups in any subgroup. There were no differences in clinical outcomes but there were more adverse events, including serious events and adverse events leading to early study drug discontinuation, in patients treated with active therapy. In this study of a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS, there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan, aliskiren, or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy. Moreover, adverse events were reported more frequently in patients assigned to active therapy.

Pulmonary arterial size and response to sildenafil in chronic thromboembolic pulmonary hypertension

BackgroundRelative area change (RAC) of the proximal pulmonary artery is a measurement of pulmonary artery distensibility and has been shown to correlate with vasoreactivity studies in patients with idiopathic pulmonary arterial hypertension. We have previously noted a relationship between invasive hemodynamic vasoreactivity testing and long-term response to sildenafil in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We therefore set out to determine whether RAC can provide useful correlatory non-invasive data.MethodsPatients recruited to a randomized, controlled trial (RCT) of sildenafil at 40 mg 3 times daily underwent additional magnetic resonance imaging (MRI) at the baseline of the trial. Eighteen patients had an MRI that led to a diagnosis of inoperable distal CTEPH or significant residual CTEPH post-operatively. The primary end-point was improvement in 6-minute walk test (6MWT) with secondary end-points of right heart catheterization–based hemodynamics, N-terminal pro–brain natriuretic peptide (NT pro-BNP) and functional class. RAC assessed by MRI was correlated with trial end-points.ResultsFourteen subjects with baseline MRI completed the protocol. RAC was the only baseline variable that correlated at 1 year to the primary end-point of improvement in 6MWT (r = 0.7, p = 0.006), and also to a change in NT pro-BNP (r = 0.59, p = 0.03). Using a cut-off of RAC over 20% there was an 87.5% sensitivity (95% confidence interval [CI]: 45% to 100%) and a 66.7% specificity (95% CI: 22% to 96%) for an improvement in 6MWT of >40 meters.ConclusionsRAC correlates with functional response to sildenafil, as measured by the 6MWT, and improved heart function, as measured by NT pro-BNP. RAC shows potential in understanding and possibly predicting treatment response.

Effects of Eprosartan on Diastolic Function and Neurohormones in Patients with Hypertension and Diastolic Dysfunction

ObjectiveTo compare the effects of an angiotensin receptor blocker(ARB)-based regimen versus a non-ARB based regimen on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction.Methods97 patients with a systolic blood pressure (SBP) ≥140 mmHg, a left ventricular ejection fraction >0.50, and echocardiographic evidence of diastolic dysfunction were randomly assignment to open-label treatment with eprosartan (with other anti-hypertensives; n = 47) or other anti-hypertensives alone (n = 50). Echocardiography, including tissue Doppler imaging (TDI), and neurohormones were done at baseline and after 6 months.ResultsMean age was 65 (±10) years and 64% was female. During 6 months of treatment, SBP decreased from 157 ± 16 to 145 ± 18 mmHg in the eprosartan group and from 158 ± 17 to 141 ± 18 mmHg in the control group (both p < 0.001; p = ns between groups). Diastolic function was unaffected in both groups and there was no correlation between changes in SBP and changes in mean TDI (r = −0.06; p = 0.58). Aldosterone levels decreased in the eprosartan group, but other neurohormones remained largely unchanged. Change in SBP was however related to the change in NT-proBNP (r = 0.26; p = 0.019).ConclusionLowering blood pressure, either with eprosartan or other anti-hypertensives in hypertensive patients with diastolic dysfunction did not change diastolic function after 6 months of treatment, but was associated with a decrease of NT-proBNP.

Early Detection of Cardiac Systolic Functional Impairment and Correlation with NT-ProBNP Change in AL Amyloidosis by Cardiac Lateral Wall Tissue Doppler S Wave.

Abstract 2814Poster Board II-790N-terminal fragment of brain natriuretic peptide is a cardiac biomarker that has prognostic significance in amyloidosis and NT-ProBNP can rapidly change after completion of chemotherapy. We and others who have previously reported such changes in NT-ProBNP to be of prognostic significance but there was no cardiac “progression” or “improvement” according to the international amyloidosis consensus criteria (Gertz et al 2005) in the majority - making this finding difficult to explain. We now report subtle changes in left ventricular systolic function using lateral wall tissue Doppler as a new robust and reproducible parameter correlating well with such changes in NT-ProBNP.Patients with cardiac amyloidosis as defined by the international consensus criteria who had good renal function (creatinine clearance >30ml/min), received chemotherapy and had a significant change in NT-ProBNP after chemotherapy were identified from the database of the UK National Amyloidosis Centre. A significant change in NT-ProBNP was defined as minimum rise or fall of 30% over the baseline pre-treatment value.Ninty seven patients with identified. All analysis was repeated on stored off line data on EchoPAC” in accordance with British Society of Echocardiography guidelines with special focus on ejection fraction (EF) (Biplane Simpson's method), longitudinal 2D strain, lateral TDI S wave (Tissue Doppler Imaging) and mean left ventricular wall thickness. At baseline the mean EF was 59%, mean LV wall thickness 13mm and mean TDI S wave velocity 0.07m/sec. 76/97 (78%) patients showed a significant increase in the NT-proBNP levels and 21/97 (22%) showed a significant a decrease. There was a significant correlation between the free light chain (FLC) level and NT-ProBNP at diagnosis (correlation coefficient 0.322; p <0.001). NT-ProBNP decreased from median 444 to 144 pMol/L (p=0.021) among patients who had a complete FLC response. There was also good correlation between the NT-ProBNP level with interventricular septal and left ventricular posterior wall thickness (spearman correlation coefficient 0.55, significance 0.01) at baseline. None of the patients had cardiac progression or improvement by echocardiography according to the international consensus criteria . In both groups of patients (increase or decrease in NT-ProBNP), there was no significant change in the LV wall thickness. In patients with a decrease in the NT-proBNP, there was no significant increase in the ejection fraction or longitudinal 2-D strain in the evaluable cases. But there was a significant improvement in the mean lateral TDI S wave (a marker of longitudinal LV systolic function) from 0.07 m/s to 0.08m/s (p=0.02) suggesting improvement in systolic function. In patients with an increase in the NT-ProBNP, there was a significant decrease in the mean EF from 60% to 56% (p=0.032). The longitudinal 2D strain also decreased significantly by mean of 10% (-13.9% to -12.6%; p=0.009) and the lateral TDI S wave also showed significant worsening with a decline from 0.09m/sec to 0.07m/sec (p <0.001).NT-ProBNP changes after chemotherapy have remained difficult to explain. The international consensus criteria for cardiac progression or improvement by echocardiography - a 2 mm change in the LV wall thickness or 20% change in EF - are relatively insensitive and the clinical criteria (change in NYHA class by 2) are not robust or reproducible to detect cardiac improvement or progression. Lateral TDI S wave is a robust and reproducible parameter that correlates well with both an increase and decrease drop in NT-ProBNP levels. This suggests that there are subtle changes to the left ventricular systolic function which correlate well with change in NT-ProBNP and are of prognostic significance. These changes in systolic function occur well before any substantial diastolic functional change or change in wall thickness. This interesting finding needs further validation in larger groups and if confirmed should be considered for incorporation in the consensus criteria for cardiac progression or improvement. Disclosures:No relevant conflicts of interest to declare.

Determinants of absolute and relative exercise-induced changes in B-type natriuretic peptides

Exercise is associated with changes in circulating B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP). However, the biological relevance of this phenomenon is poorly examined. We sought to assess determinants of absolute (Δ) and relative (Δ%) exercise-induced changes in BNP and NT-proBNP. BNP (n = 418) and NT-proBNP (n = 478) at rest and peak exercise were measured in patients undergoing symptom-limited cycle ergometer tests. Multivariate logistic regression was performed to identify predictors of high ΔBNP/ΔNT-proBNP and high ΔBNP/Δ%NT-proBNP defined as their highest quartiles (Q4). The median (interquartile range) ΔBNP and ΔNT-proBNP was 12 (0-28) pg/ml and 7 (2-21) pg/ml respectively, and Δ%BNP and Δ%NT-proBNP was 21 (0-46) % and 7 (3-12) % respectively. Higher BNP [odds ratio (OR) 3.92 per ln unit; p < 0.001] or NT-proBNP [OR 4.88 per ln unit; p<0.001] at rest was the strongest predictor of ΔBNP in Q4 (≥ 28 pg/ml) or ΔNT-proBNP in Q4 (≥ 21 pg/ml). In contrast, higher maximal work rate expressed as the percentage of the predicted value (OR 1.015 per %; p = 0.007) was the only independent predictor of Δ%BNP in Q4 (≥ 46%), and lower resting heart rate (OR 0.97 per bpm; p = 0.001) and lower age (OR 0.95 per year; p = 0.001) were the only independent predictors of Δ%NT-proBNP in Q4 (≥ 12%). Higher ΔBNP and ΔNT-proBNP primarily reflected higher BNP and NT-proBNP plasma levels at rest. In contrast, higher Δ%BNP and Δ%NT-proBNP were associated with several prognostically favorable features, indicating that higher Δ%BNP and Δ%NT-proBNP may be markers of health rather than disease.

The Change in B-Type Natriuretic Peptide Levels Over Time Predicts Significant Rejection in Cardiac Transplant Recipients

B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection. N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations. A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters. There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

Non-invasive tissue Doppler imaging pulmonary capillary wedge pressure measurement improves NT-proBNP prognostic value in heart failure

Objective — The aim of the present study was to investigate whether the improvement of pulmonary capillary wedge pressure (PCWP) non-invasively assessed with tissue Doppler imaging is able to predict prognosis and cardiac-related mortality in patients with heart failure (HF), as previously demonstrated for NT-proBNP.Methods — We prospectively studied 23 patients (74 ± 10 y; 17 M, 6 F) with acute HF. NT-proBNP and PCWP were measured at admission and discharge. NT-proBNP concentrations were determined by a chemiluminescent immunoassay kit. PCWP was assessed using the ratio of transmitral E velocity to the early diastolic mitral annulus velocity (E’), with the formula PCWP = 1.9 + 1.24 (E/E’). Patients were divided in two groups according to the clinical end-point based on cardiac death and hospital readmission for HF.Results — After a mean follow-up of 230 days, 10 patients reached the end-point (group A), while 13 patients resulted event-free (group B). In group B, NT-proBNP values significantly decreased (3816 ± 7424 vs. 6799 ± 10537 pg/mL, P < 0.01) and PCWP improved (17 ± 7 vs. 23 ± 12 mmHg, P < 0.01).The decrease in both NT-proBNP and PCWP values was able to identify the majority of patients (77%) with an event-free survival at follow-up, whereas 70% of patients who reached the end-point had discordant changes in NT-proBNP and PCWP (x2 = 5.06, P < 0.05).Conclusions — The combination of a biochemical marker such as NT-proBNP and a new indicator of LV filling pressure (E/E’) allows to estimate the prognostic impact of standard medical therapy even in a small group of HF patients.

Relation of N-Terminal Pro B-Type Natriuretic Peptide Levels After Symptom-Limited Exercise to Baseline and Ischemia Levels

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.

Role of NT-ProBNP to Assess the Adequacy of Treatment Response in AL Amyloidosis.

We report the use of NT-ProBNP (N-terminal fragment of brain natriuretic peptide) as an independent marker to identify patients with AL amyloidosis whose clonal response to chemotherapy is inadequate. The aim of chemotherapy is to allow improvement in amyloidotic organ function but the significant time lag often means that patients are either over or under treated. Use of biomarkers (such as BNP and NT-ProBNP) for risk stratification is an area of increasing interest.200 patients with AL amyloidosis diagnosed between 2004–2007, who had completed one line of treatment and had a complete results available prior to and six month from the start of treatment, were identified from the databases of the Amyloidosis centres in Pavia, Italy and London, UK. Organ involvement and response was assessed according to the international consensus criteria (Gertz et al 2005). NT-ProBNP change was deemed significant if there was a rise or fall of both 30% and >300 ng/L over the starting value. Kaplan-Meier and Cox regression were used for survival analysis as appropriate. The median age was 63 yrs (range 38–83) and the median number of organs involved was 2. 132 (66%) had cardiac involvement, 150 (75%) had renal and 42 (21%) had liver involvement at presentation. 115 (56%) responded to chemotherapy with a complete response (CR) in 34 (17%) and a partial response in 81 (40%).At baseline, median NT-ProBNP was 1865 ng/L (range 50–70144) and was >332 ng/L (the cut-off reported as significant by Dispenzieri et al, J Clin Oncol 2004) in 159 patients (80%). The median follow-up was 23 months. The median overall survival (OS) has not been reached with an estimated 2 yr survival of 71%. Patients with cardiac involvement had worse outcomes (OS 29 mo vs. not reached; p =0.001) whereas renal, liver, neuropathy, soft tissue involvement, the light chain type or presence of a measurable M protein did not significantly impact survival. Haematologic responders had a significantly better overall survival (median not reached) than non-responders (median 22 months; p<0.0001) with those achieving CR having significantly better survival than PR (estimated 4 year survival of 94% and 65% respectively; p=0.005).The NT-proBNP increased and decreased significantly in 45 (22%) and 92 (46%) respectively - with the latter group achieving lower FLC concentration after treatment (27.6 vs. 96.4 mg/L, p<0.0001).16 of the 22 (73%) patients with heart involvement who obtained CR also has decreases in NT-ProBNP. Patients without significant NT-ProBNP decrease (median OS 29 months vs. not reached) or with significant increase (median OS 20 months vs. not reached) had significantly poorer outcome (p<0.0001). The impact of this was most marked in patients achieving a PR – in this group, the estimated 3 year survival was 48% for patients in whom there was an increase in NT-ProBNP (not significantly different from the non-responders) vs. 86% for patient in whom there was a decrease (not significantly different from those who achieved CR) (log rank p<0.0001, see figure). On multivariate analysis, cardiac involvement and change NT-ProBNP were highly significant independent prognostic factors.In summary, patients who have a fall in NT-ProBNP have excellent outcomes irrespective of the degree of haematological response. Conversely, the failure to see a fall or to see an increase in NT-ProBNP clearly identifies a group of patients with AL amyloidosis, who despite a haematologic response to treatment, have significantly poorer outcomes. A prospective randomised study to see the effects of rapidly changing to alternative treatment in the latter groups is being planned. [Display omitted]

Abstract 5010: Determining the Plasticity of Cardiovascular Risk in the Elderly: A role for serial NT-proBNP measurement

In the elderly, with decades of exposure to cardiovascular (CV) risk factors, CV prognosis is often considered static. We hypothesized that CV risk is dynamic reflected by changes in NTproBNP over time. We measured NTproBNP at baseline and after 2–3 years in the Cardiovascular Health Study. Long-term risk of CV death according to change in NTproBNP was estimated with the Kaplan-Meier method. We used Cox models to test if effect of change in NTproBNP was independent of demographic and CV risk factors, baseline NTproBNP, renal function, coronary disease, and CV medications. Participants were categorized at baseline as &lt; (low) or &gt;=190pg/mL (high) levels, based on an observed increase in risk above this level. A significant change in NTproBNP category was defined as a change of &gt;25% to a level above or below this cut-point, based on the reported biological variability of NTproBNP. Change in NTproBNP was also evaluated as a continuous measure. Serial NTproBNP levels were measured in 2,975 (86%) of 3,469 participants (age 75±5 years) without heart failure and who had a follow-up visit. CV death was different between those with low levels that remained low (n=1,774) vs. those with low levels that became high (n=468) (1.1 vs. 2.7 per 100 person-yrs, p&lt;.001) and those with high levels that remained high (n=621) vs. those with high levels that became low (n=112) (4.2 vs. 1.6 per 100 person-yrs, p&lt;.001) (figure ). As a continuous measure, change in NTproBNP was linearly associated with CV mortality risk after adjustment (per Ln-fold increment: RR=1.47, p&lt;.001). Dynamic changes in NTproBNP levels reflect dramatic change in CV prognosis in the elderly. Proportion without Cardiovascular death, by initial and follow-up NT-proBNP

The change of the urine NT-proBNP in patients With chronic heart failure

目的 探讨尿NT-proBNP在慢性心力衰竭(chroniC heart failare,CHF)中的变化规律,与心功能分级的相关性,进一步探讨尿NT-proBNP对慢性心力衰竭的诊断价值.方法 49例入院治疗的CHF患者(NYHA Ⅱ-Ⅳ级)和24例健康体检者,测定血NT-proBNP、尿NT-proBNP,超声心动图检测左室舒张末室间隔厚度、左室舒张末期内径、左室收缩末期内径、左室射血分数.结果 ①CHF组尿NT-proBNP水平和血NT-proBNP水平明显高于正常对照组,分别为(65.47±41.34)pg/ml vs(17.95±7.22)pg/ml,(3204.47±2067.34)pg/ml vs(40.60±1 5.38)pg/ml,P均<0.01.尿NT-proBNP水平与血NT-proBNP水平呈正相关(r=0.639,P<0.001).②随心功能的恶化,尿NT-proBNP水平逐渐升高.尿NT-proBNP与NYHA分级、左室舒张末期内径呈正相关(P均<0.001),与左室射血分数呈负相关(P<0.001).多元逐步回归分析显示与logNT-proBNP独立相关的变量是血NT-proBNP、左室射血分数及NYHA分级.③尿NT-proBNP、血NT-proBNP对CHF诊断价值以ROC曲线下面积表示,分别为0.837(95%可信限:0.758～0.952),0.883(95%可信限:0.809～0.963).④根据ROC曲线,以诊断CHF的敏感度与特异度之和的最高值作为截断值,尿NT-proBNP的截断值为19.01pg/ml.结论 ①在正常人和CHF患者尿中可检测到NT-proBNP.②CHF患者尿NT-proBNP水平明显高于对照组,而且尿NT-proBNP水平与血NT-proBNP水平呈正相关.③CHF患者随心功能的恶化(NYHA Ⅱ-Ⅳ级),尿NT-proBNP水平逐渐升高.尿NT-proBNP水平与LAD无相关性,与LVEDD、NYHA分级呈正相关,与LVEF呈负相关.④尿NT-proBNP在检测CHF中与血NT-proBNP具有相似的诊断价值。

Plasma NT-proBNP increases in response to LPS administration in healthy men

Circulating levels of B-type natriuretic peptide (BNP) and NH(2)-terminal-proBNP (NT-proBNP) increase in response to volume overload and help in the differential diagnosis of acute heart failure. Elevated plasma BNP levels are observed also in sepsis and do not always correspond to left ventricular dysfunction. Here, we investigated plasma NT-proBNP fluctuations in response to human bacterial endotoxinemia, an experimental model of systemic infection and inflammation. Escherichia coli endotoxin (LPS) (2 ng/kg) was administered to 10 healthy volunteers in a randomized, placebo-controlled, cross-over design. Plasma NT-proBNP, C-reactive protein (CRP), COOH terminal pro-endothelin-1 (CT-proET-1), and midregional-pro-adrenomedullin (MR-proADM) were measured at hourly intervals for 6 h. LPS administration induced a continuous increase in plasma NT-proBNP that reached peak values after 6 h (40.7 +/- 7.9 vs. 16.1 +/- 3.2 pg/ml in placebo days, mean +/- SE; P = 0.023). The profile of changes in NT-proBNP correlated to changes in body temperature (P < 0.001), heart rate (P = 0.005), CRP (P < 0.001), and CT-proET-1 (P = 0.008), but not to blood pressure values. Our results demonstrate that plasma NT-proBNP increases in a model of systemic infection/inflammation in healthy men with normal heart function. This finding emphasizes the necessity to consider concomitant infections when interpreting elevated circulating NT-proBNP concentrations.

Changes of NT proBNP correlated with the regression of left ventricular hypertrophy in patients with aortic valve replacement

Eun-Seok Jeona,∗, Soo-Hyeon Yuna, hyun Mi Songa, Eun-Seon Jua, Sang Hoon Leea, Myeong-Chan Chob, Dong Ju Choi c, Jae-Joong Kimd, Kyu Hyung Ryue a Cardiac and Vascular Center, SamsungMedical Center, South Korea b Cardiology, Chungbuk National University Hospital, South Korea c Cardiology, Seoul National University Hospital, South Korea d Cardiology, Asan Medical Center, Ulsan Medical University, South Korea e Cardiovascular Center, Kunkook University Hospital, South Korea

NT‐proBNP response to dobutamine stress echocardiography predicts left ventricular contractile reserve in dilated cardiomyopathy

Brain natriuretic peptide (BNP) and left ventricular (LV) inotropic reserve are major prognostic indexes in heart failure (HF). To investigate the relationship between N-terminal-proBNP (NT-proBNP) changes in response to dobutamine stress echocardiography (DSE) and the LV inotropic reserve, in HF patients with dilated cardiomyopathy (DC). We studied 41 patients with DC, LVEF 31.6+/-7.7%, NYHA class II-III and 15 controls. Plasma NT-proBNP levels were measured before and 60 min after three 5-min stages of dobutamine (5 to 15 microg/kg/min). Based on NT-proBNP changes in response to dobutamine, patients were categorized into two groups: In Group A circulating NT-proBNP levels fell (-16.6+/-7.8%), and in Group B they increased (8.4+/-9.1%). Group A had a marked improvement in WMSI compared to Group B (32.1+/-9.7% vs. 18.8+/-15.9%, p<0.001). Multivariate analysis showed that NT-proBNP changes were an independent predictor of LV inotropic reserve (b= -0.55, p<0.001). A reduction of 21.3% in plasma NT-proBNP levels in response to dobutamine predicted an improvement in WMSI of >25% with a sensitivity of 100% and a specificity of 92.3%. NT-proBNP changes in response to dobutamine reflect improvement in LV contractility and constitute an independent predictor of LV inotropic reserve in patients with DC.

Prognostic value of sequential measurements of amino‐terminal prohormone of B‐type natriuretic peptide in ambulatory heart failure patients

We evaluated the prognostic value of sequential NT-proBNP values in ambulatory heart failure patients after discharge, investigating whether the current value or the recent percent change is more important. In 166 patients, NT-proBNP was measured at discharge from heart failure hospitalisation and three months later. The combined endpoint of death or heart failure rehospitalisation was evaluated after a maximum of 18 months or at follow-up closure. During a mean observation time of 14+/-4 months, 63 patients (38%) reached the endpoint. In multiple Cox analysis, NT-proBNP three months after discharge (NT-proBNP-3Mo) and NT-proBNP percent change (NT-proBNP-%change) were the only independent predictors of the endpoint among various clinical and laboratory variables. After definition of a high- (n=83, 57% endpoints) and a low-NT-proBNP patient subgroup (n=83, 19% endpoints) according to the median NT-proBNP-3Mo (1751 pg/ml), NT-proBNP-%change was the strongest predictor in the high-NT-proBNP subgroup. In the low-NT-proBNP subgroup, NT-proBNP-3Mo was the only independent predictor. In ambulatory heart failure patients, the prognostic value of sequential NT-proBNP measurements depends on the magnitude of the current NT-proBNP value. Recent percent changes in NT-proBNP provide important prognostic information in patients with high NT-proBNP but not in patients with low NT-proBNP.

Hemodynamic improvement of acutely decompensated heart failure patients is associated with decreasing levels of NT-proBNP

Background Successful therapy in chronic clinically stable heart failure is reflected by decreasing serum NT-proBNP levels. This study evaluates therapy monitoring by NT-proBNP in comparison to invasively measured hemodynamic parameters in acutely decompensated heart failure patients. Methods and results In 25 acutely decompensated chronic heart failure patients (NYHA III–IV, Cardiac Index (CI) ≤ 2.5 l/min/m 2 and a PCWP ≥ 15 mm Hg) changes in NT-proBNP and invasive hemodynamics were compared. Hemodynamic improvement in the first 24 h (CI ≥ 30% and PCWP ≤ 30%, compared to baseline) was associated with decreasing NT-proBNP levels; which was not seen in patients without hemodynamic improvement. To discriminate between responders and non-responders, a decline to < 80% of the baseline NT-proBNP in the first 24 h was the best cut-off. Conclusion Hemodynamic improvement in acutely decompensated heart failure patients is associated with decreasing NT-proBNP levels.

Effect of Beta-blockade and ACE Inhibition on B-type Natriuretic Peptides in Stable Patients with Systolic Heart Failure

The long-term effect of beta-blockade on the plasma levels of natriuretic peptides BNP and its N-terminal counterpart, NT-proBNP, as risk markers in heart failure (HF) is obscure. Stable systolic HF patients from the CARMEN study were divided in groups matching their randomised treatment allocation: Carvedilol, enalapril or carvedilol+enalapril. Changes in BNP and NT-proBNP from baseline to 6 months maintenance visit were evaluated in each treatment arm. Furthermore, the prognostic value of BNP and NT-proBNP during monotherapy with carvedilol was assessed with univariate Cox proportional hazards models using a combined endpoint of all cause mortality and cardiovascular hospitalisation. NT-proBNP and BNP were significantly reduced after six months treatment with enalapril (NT-proBNP 1,303 to 857 pg/ml (P < 0.001), BNP 119 to 85 pg/ml (P < 0.001)) or carvedilol+enalapril (NT-proBNP 1,223 to 953 pg/ml (P = 0.003), BNP 117 to 93 pg/ml (P = 0.01)). In contrast, no change was observed in the carvedilol group (NT-proBNP 907 to 1,082 pg/ml (P = 0.06), BNP 114 to 130 pg/ml (P = 0.15). The prognostic value of NT-proBNP and BNP was maintained in the carvedilol group (NT-proBNP HR 1.018 95% CI (1.005-1.032), BNP 1.171 (1.088-1.260)). Treatment of HF patients with carvedilol alone does not reduce levels of natriuretic peptides, but treatment with enalapril does. Both BNP and NT-proBNP predict death and hospitalisation in HF patients treated with carvedilol for six months. The clinical implication of our results is that NT-proBNP and BNP can be used as risk markers of death and cardiovascular hospitalisations in systolic HF patients receiving carvedilol without ACE inhibition.

Amino-Terminal Pro–B-Type Natriuretic Peptide Testing for Inpatient Monitoring and Treatment Guidance of Acute Destabilized Heart Failure

Although typically elevated at presentation in the context of destabilized heart failure (HF), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) values typically decrease rapidly among patients who have a favorable response to therapy. Given this, it is natural to examine the relation between NT-proBNP and therapeutic interventions for acute HF. Both presentation and posttreatment NT-proBNP concentrations have some value for prognostication of recurrent HF hospitalization or death. However, the percent change in NT-proBNP after treatment for acute HF may be a more powerful method for risk stratification. Although prospective studies on the effect of NT-proBNP measurement in guiding therapy in acute destabilized HF are lacking, observational data suggest that a 30% decrease in NT-proBNP values during hospitalization is a reasonable goal. If a baseline measure of NT-proBNP is not available, an NT-proBNP level <4,000 ng/L after acute treatment is an alternative goal. Because the criteria for determining restabilization from destabilized HF prominently include clinical and routine laboratory testing rather than NP measures, the frequency of NT-proBNP measurement should not be excessive in patients with acute HF, with measures at baseline/presentation and after perceived recompensation to evaluate for the desired decrease in NT-proBNP concentrations. A remeasurement of NT-proBNP may also be useful for evaluation of new or worsened symptoms. In those patients without a decrease in NT-proBNP despite perceived recompensation from HF, a review of adequacy of treatment, goals of therapy, and consideration of prognosis is recommended.