NT-proBNP in heart failure: therapy decisions and monitoring

With increasing cardiac dysfunction, a complex neurohormonal response results in increasing circulating levels of an array of plasma hormones. Increments in plasma levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) and their amino-terminal congeners are more closely related to cardiac structure and function and to cardiovascular prognosis than changes in other plasma neurohormones. Reports suggest that changes in plasma BNP levels in the course of treatment of acutely decompensated heart failure provide a more powerful prognostic indicator of the likelihood of survival or recurrent decompensation than symptomatic assessment. This observation requires a randomised controlled trial in which changes in peptide levels determine aggression and duration of in-patient therapy in order to establish whether this indicator can improve results from management of acute in-patient heart failure. Plasma BNP or NT-proBNP is a powerful independent predictor of mortality and morbidity in long-term follow-up of heart failure cohorts. In addition, it appears likely to be a good predictor of beneficial response to the addition of beta blockade to anti-heart failure pharmacotherapy. Finally, adjustment of therapy for heart failure according to serial measurements of NT-proBNP promises to improve outcomes in comparison with adjusting therapy according to unassisted clinical acumen.     

The correlation of left atrial volume index to the level of N-terminal pro-BNP in heart failure with a preserved ejection fraction

Background: Patients with heart failure with a preserved ejection fraction (HFPEF) have high N‐terminal pro‐B‐type natriuretic peptide (NT‐pro‐BNP) level and a high ratio of early transmitral inflow to diastolic velocity of the mitral annulus (E/E′) derived from tissue Doppler imaging (TDI). Because left atrial volume indexed to body surface area (LAVI) is believed to reflect chronic diastolic dysfunction, we assessed the ability of LAVI and E/E′ ratio to predict NT‐pro‐BNP level in patients with HFPEF. Methods: One hundred forty‐eight patients with HFPEF (ejection fraction ≥ 50%, NT‐pro‐BNP ≥ 100 pg/ml) underwent conventional echocardiography including LAVI and E/E′ ratio, which were compared with NT‐pro‐BNP level. Results: In the overall patient population, modest correlations were found between NT‐pro‐BNP level and peak systolic TDI (S′) (P = 0.009), LAVI (P = 0.009), and E/E′ ratio (P = 0.017). However, in patients with E/E′ ratio ≥13, LAVI was the most important predictor of NT‐pro‐BNP level (P < 0.001), whereas in those with E/E′ ratio <13 it was S′ (P < 0.001) in multivariate analysis. Conclusion: In patients with HFPEF evidenced by high NT‐pro‐BNP level, LAVI correlates with NT‐pro‐BNP level in the setting of elevated E/E′ ratio. However, in the setting of low E/E′ ratio, LAVI does not seem to be associated with NT‐pro‐BNP level.     

Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score

Background

NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score.

Methods

This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score.

Results

One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p = 0.0027) and the IDI (0.037; p = 0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798–0.880) and the Hosmer–Lemeshow statistic was 1.23 (p = 0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711–0.817); the Hosmer–Lemeshow statistic was 2.76 (p = 0.251), after recalibration.

Conclusions

The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.     

慢性心力衰竭患者N端脑钠肽前体、内皮素与心功能的关系

目的探讨慢性心力衰竭(心衰,CHF)患者N端脑钠肽前体(NT-proBNP)、内皮素(ET)水平与心功能的关系。方法入选56例CHF患者作为研究对象,29例心功能正常者作为对照组。心衰患者按照NYHA分级分为心功能Ⅱ级、Ⅲ级、Ⅳ级3个亚组,分别测定患者NT-proBNP、ET水平,同时用心脏彩色多普勒超声心动仪测定左室射血分数(LVEF)和左室舒张末期内径(LVDD)并进行组间比较及相关性分析。结果对照组及CHF心功能Ⅱ级、Ⅲ级、Ⅳ级亚组的患者NT-proBNP水平分别为(336.24±41.25)ng/ml、(1761.35±21.43)ng/ml、(2693.45±41.54)ng/ml、(3161.26±67.56)ng/ml,ET水平分别为(19.89±11.35)ng/L、(48.60±21.25)ng/L、(61.56±31.68)ng/L、(161.67±46.56)ng/L。对照组患者及CHF心功能Ⅱ级组、Ⅲ级组、Ⅳ级组患者血浆NT-proBNP、ET水平呈逐渐增高趋势,差异具有显著统计学意义(P0.01)。除心功能Ⅱ级组与心功能Ⅲ级组间ET与LVEF水平比较无统计学差异(P0.051),其余各组间NT-proBNP、ET水平及LVEF、LVDD水平比较,均有显著统计学差异(P均0.01)。NT-proBNP与心功能分级呈正相关(r=0.769,P0.05),与LVDD呈正相关(r=0.606,P0.05),与LVEF呈负相关(r=-0.656,P0.05)。ET水平与心功能分级呈正相关(r=0.357,P0.05),与LVDD呈正相关(r=0.265,P0.05),与LVEF呈负相关(r=-0.274,P0.05)。结论 CHF患者NT-proBNP与ET水平随心力衰竭程度的加重而相应升高,与心功能分级有良好的相关性,对心力衰竭患者心力衰竭严重程度及预后的评价有意义。     

B型利钠肽测定对充血性心力衰竭患者预后评估的研究

目的探讨B型利钠肽(BNP)对充血性心力衰竭(CHF)患者预后评估的价值。方法对343例因CHF住院的患者,入院时测定BNP,同时测定左心室射血分数(LVEF)、左心室舒张末内径(LVDD),胸片测定心胸比率(CTR)。出院前复查一次,随访观察患者3个月内的病死率、再住院率,作为终末事件。结果①心功能Ⅰ、Ⅱ、Ⅲ、Ⅳ级患者的BNP水平分别为(157±15)pg/ml、(341±22)pg/ml、(597±33)pg/ml、(1245±38)pg/ml。心功能越差,BNP越高,不同的NYHA心功能分级,BNP差异有显著性(P<0.001)。②BNP水平与LVEF呈明显负相关(r=-0.8,P<0.05)。③343例患者,住院期间死亡5例,3月内再次入院22例。事件组27例,其BNP水平为(1683±124)pg/ml,非事件组316例,其BNP水平为(468±48)pg/ml。两组差异有显著性(P<0.001)。4.将出院前BNP>1500pg/ml作为评估终末事件的界值,其预测预后的敏感性为96.3%,特异性为92.7%。5.对CHF患者的性别、年龄、LVEF、LVDD、BNP、病因等进行多元逐步回归分析,BNP与预后关系最密切。结论本文提示BNP较LVEF评价CHF更确切可靠,动态观察BNP变化水平是CHF患者有效的预后判断指标。     

Using BNP to develop a risk score for heart failure in primary care.

AIMS: Chronic heart failure is a common condition with high mortality. Accurate diagnosis in primary care is difficult. Elevated B-type natriuretic peptide (BNP) is associated with left ventricular systolic dysfunction and increased mortality. Prognostic scoring systems using BNP may help to stratify risk in primary care patients. The aim of this research was to establish the independent variables which predict mortality in a primary care population-prescribed loop diuretics and to generate and validate a scoring system for heart failure in general practice. METHODS AND RESULTS: Five hundred and thirty-two patients were followed up for a mean of 6.4 years after attending a research clinic for clinical assessment, electrocardiogram (ECG), echocardiography, and BNP. Multivariate analysis was used to establish independent prognostic variables and to generate a prognostic scoring system. The score generated was [0.50 x BNP+5 x age+50 x (CVA+sex+diabetes+ECG)]. The cut-off scores for risk groups were; 25th percentile, 411; 50th percentile, 475; 75th percentile, 524; Harrell's c=0.75. CONCLUSION: Developing prognostic scoring systems provides a means of risk stratifying patients without relying on a single cut-off diagnostic value for BNP. Further validation of such scoring systems may improve future management of community heart failure patients.     

Direct comparison of transcardiac difference between brain natriuretic peptide (BNP) and N-terminal pro-BNP in patients with chronic heart failure

BACKGROUND: Direct comparison of transcardiac increase in brain natriuretic peptide (BNP) and NT-pro-BNP has not been performed previously. AIMS: To evaluate the relation between BNP and NT-pro-BNP secretion, plasma levels and renal function. METHODS: We measured the plasma levels of BNP and NT-pro-BNP in the aortic root and coronary sinus in 326 consecutive patients with chronic heart failure (CHF). Patients were divided into two groups [group I: estimated glomerular filtration rate (eGFR)>or=60 mL/min and group II: eGFR<60 mL/min]. RESULTS: The molar level of the transcardiac increase in NT-pro-BNP is lower than that of BNP. There were no differences in haemodynamics or the transcardiac gradient of BNP and NT-pro-BNP between group I and group II. The molar ratio of the plasma NT-pro-BNP to BNP was significantly higher in group II than in group I. By stepwise multivariate analyses, not only the left ventricular (LV) ejection fraction and LV end-diastolic pressure, but also eGFR, LV mass index (LVMI) and haemoglobin were independent predictors of plasma NT-pro-BNP and BNP. CONCLUSION: The molar level of the transcardiac increase in NT-pro-BNP is lower than that of BNP; however, the influence of renal function on plasma NT-pro-BNP is greater than that on BNP.     

Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure

BACKGROUND: B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence). METHODS: We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers. RESULTS: While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value. CONCLUSION: Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.     

B-type natriuretic peptide measurement in heart failure

Serum testing for the hormone B-type natriuretic peptide (BNP) may have clinical utility in congestive heart failure (CHF). This hormone is secreted predominantly by the left ventricular myocardium in patients with CHF. Measurement of serum BNP may improve diagnosis of CHF and may also help guide therapy in patients with CHF. The literature regarding the clinical utility of BNP measurement in CHF is reviewed.     

Incremental prognostic value of changes in B-type natriuretic peptide in heart failure

Purpose

B-type natriuretic peptide is one of the most sensitive and specific biohumoral markers of heart failure. We hypothesized that B-type natriuretic peptide changes during treatment of heart failure may provide independent information on disease progression and outcome in patients enrolled in the Val-HeFT trial.

Methods

Patients were divided into four groups according to concentrations of B-type natriuretic peptide at baseline versus 4 months (n = 3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL): low→low (stable below median, 44%-46%), high→high (stable above median, 32%-37%), high→low (above to below median, 12%-14%), and low→high (below to above median, 6%-9%). Cox multivariate regression analysis was used to assess the risk of death and morbidity, with adjustment for baseline B-type natriuretic peptide concentrations.

Results

Patients who improved their B-type natriuretic peptide at 4 months (high→low) had a similar risk for mortality (hazard ratio = 1.191, 95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low→low patients. Conversely, patients who worsened in their B-type natriuretic peptide (low→high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P <.0001) higher than patients in the low→low group, and indistinguishable from the high→high group. Worsening of B-type natriuretic peptide (low→high) was associated with 0.03 cm/m² increase in left ventricular end-diastolic diameter, whereas it decreased by 0.10 cm/m² in high→low and low→low groups (P <.001).

Conclusions

Changes in B-type natriuretic peptide over time with respect to a threshold value of 97 pg/mL convey an independent and additional prognostic value compared with a single determination of B-type natriuretic peptide in a large population of patients with chronic symptomatic heart failure and might be helpful in the management of these patients.     

Atorvastatin therapy is associated with reduced levels of N-terminal prohormone brain natriuretic peptide and improved cardiac function in patients with heart failure

BACKGROUND: Statins have been suggested to improve cardiac function, but the evidence underlying beneficial effects of statins in heart failure (HF) is insufficient. We analyzed plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels and cardiac function in patients with HF of various etiologies, and who were treated with or without statins. HYPOTHESIS: Statin treatment is associated with improved cardiac function in HF. METHODS: The study cohort consisted of 139 consecutive male patients receiving atorvastatin (n = 44), simvastatin (n = 29), pravastatin (n = 19), or no statin (n = 47). The NT-proBNP levels were measured using electroluminescence immunoassay. Left ventricular end-diastolic diameter (LVEDD), fractional shortening (FS), and ejection fraction (EF) were determined by echocardiography. RESULTS: Patients receiving atorvastatin presented with reduced NT-proBNP levels (1,552 +/- 3,416 versus 3,771 +/- 6,763 pg/mL; p < 0.01), and improved values of LVEDD (65.2 +/- 8.9 versus 70.7 +/- 10.9 mm; p < 0.05) and EF (33.2 +/- 12.6 versus 28.2 +/- 9.6%; p < 0.05). By contrast, plasma NT-proBNP and cardiac parameters in patients treated with statins other than atorvastatin did not significantly differ from control. Atorvastatin treatment was equally effective in patients with ischemic and nonischemic HF. CONCLUSIONS: Atorvastatin treatment is associated with improved cardiac function in HF, and may represent an additional option for patients with this disease.