In spite of the introduction of mild therapeutic hypothermia (MTH), mortality rates remain high in patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA). To date, no accurate and independent biomarker to predict survival in these patients exists. B-type natriuretic peptide (BNP) was found to provide both prognostic and diagnostic value in various cardiovascular diseases, including survival to hospital discharge in patients with ROSC. However, the biologically inactive counterpart of BNP, NT-proBNP, was found to be a more stable and accurate analyte. The current retrospective observational study investigates the value of NT-proBNP to predict 28-day mortality in post-CA patients treated with MTH, as well as the dynamics of NT-proBNP during MTH.
NT-proBNP levels were measured in post-CA patients cooled via cold intravenous saline infusion and water-circulating body wraps (Medi-Therm®, Gaymar). Plasma samples were obtained before cooling was started, at the start and end of the maintenance phase and at the end of rewarming.
250 patients, admitted between 2009 and 2013, had NT-proBNP levels measured on ICU admission and were included for the evaluation of NT-proBNP as a prognostic marker. In the 28 days following ICU admission, 114 patients died (46%). Non-survivors had significantly higher NT-proBNP (median 1448 ng/l, IQR 366–4623 vs median 567 ng/1, IQR 148–1899; P < 0.001) levels on ICU admission. Unadjusted odds ratios for 28-day mortality were 1.7 (95% CI 0.8-3.5), 1.6 (0.8-3.3) and 3.6 (1.7-7.5) for increasing quartiles of NT-proBNP as compared to the lowest quartile. Adjusted odds ratios were 1.1 (95% CI 0.5-2.5), 1.1 (0.5-2.5) and 1.6 (0.7-3.8), respectively. A cut-off value of 834 ng/l achieved a sensitivity of 58% and a specificity of 58% to predict 28-day mortality. Of 113 patients, NT-proBNP values of each MTH phase were available and grouped in decreased or increased levels in time. Both decreases and increases of NT-proBNP values were observed during the MTH phases, but presence of either was not associated with outcome.
High NT-proBNP plasma concentrations on ICU admission are associated with high 28-day mortality in post-CA patients treated with MTH in a univariate analysis, but not in a multivariate analysis. Increases or decreases of NT-proBNP levels during MTH appear unrelated to 28 day mortality.
Cardiac arrest; Mild therapeutic hypothermia; Natriuretic peptides; NT-proBNP
The performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) to predict clinical outcomes in ICU patients is unimpressive. We aimed to assess the prognostic value of NT-proBNP, CRP or the combination of both in unselected medical ICU patients.
A total of 576 consecutive patients were screened for eligibility and followed up during the ICU stay. We collected each patient's baseline characteristics including the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, NT-proBNP and CRP levels. The primary outcome was ICU mortality. Potential predictors were analyzed for possible association with outcomes. We also evaluated the ability of NT-proBNP and CRP additive to APACHE-II score to predict ICU mortality by calculation of C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices.
Multiple regression revealed that CRP, NT-proBNP, APACHE-II score and fasting plasma glucose independently predicted ICU mortality (all P < 0.01). The C-index with respect to prediction of ICU mortality of APACHE II score (0.82 ± 0.02; P < 0.01) was greater than that of NT-proBNP (0.71 ± 0.03; P < 0.01) or CRP (0.65 ± 0.03; P < 0.01) (all P < 0.01). As compared with APACHE-II score (0.82 ± 0.02; P < 0.01), combination of CRP (0.83 ± 0.02; P < 0.01) or NT-proBNP (0.83 ± 0.02; P < 0.01) or both (0.84 ± 0.02; P < 0.01) with APACHE-II score did not significantly increase C-index for predicting ICU mortality (all P > 0.05). However, addition of NT-proBNP to APACHE-II score gave IDI of 6.6% (P = 0.003) and NRI of 16.6% (P = 0.007), addition of CRP to APACHE-II score provided IDI of 5.6% (P = 0.026) and NRI of 12.1% (P = 0.023), and addition of both markers to APACHE-II score yielded IDI of 7.5% (P = 0.002) and NRI of 17.9% (P = 0.002). In the cardiac subgroup (N = 213), NT-proBNP but not CRP independently predicted ICU mortality and addition of NT-proBNP to APACHE-II score obviously increased predictive ability (IDI = 10.2%, P = 0.018; NRI = 18.5%, P = 0.028). In the non-cardiac group (N = 363), CRP rather than NT-proBNP was an independent predictor of ICU mortality.
In unselected medical ICU patients, NT-proBNP and CRP can serve as independent predictors of ICU mortality and addition of NT-proBNP or CRP or both to APACHE-II score significantly improves the ability to predict ICU mortality. NT-proBNP appears to be useful for predicting ICU outcomes in cardiac patients.
Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS.
Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP® assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution.
Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 ± 21 pg/mL in group A versus 209 ± 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001).
Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.
To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure.
Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied.
We analyzed the relationship between baseline NT-proBNP and peak VO2 or distance in the 6 minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak VO2 or distance in the 6 minute walk test in the context of other clinical variables. Receiver operator curve (ROC) analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO2 < 12 mL/kg/min.
NT-proBNP was the most powerful predictor of peak VO2 (partial R2=0.13, p<0.0001) out of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6 minute walk test, this relationship was weaker than that for peak VO2 (partial R2 = 0.02, p<0.0001). For both peak VO2 and distance in the 6 minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. ROC analysis suggested NT-proBNP had moderate ability to identify patients with peak VO2 < 12 mL/kg/min (c-index=0.69).
In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO2 and a significant predictor of distance in the 6 minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO2 who might be considered for cardiac transplantation. These data suggest that, while hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables.
Heart failure; exercise; biomarker; clinical trials
Background and aims: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis.
Patients and methods: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation.
Results: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls.
Conclusion: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.
brain natriuretic peptide; cardiac dysfunction; cirrhotic cardiomyopathy; pro-brain natriuretic peptide; QT interval; cardiac ventricular peptides
Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in evaluating heart failure, but its role in evaluating patients with shock in the intensive care unit (ICU) is not clear.
Forty-nine consecutive patients in four different ICUs with shock of various types and with an indication for pulmonary artery catheter placement were evaluated. Analyses for NT-proBNP were performed on blood obtained at the time of catheter placement and results were correlated with pulmonary artery catheter findings. Logistic regression identified independent predictors of mortality.
A wide range of NT-proBNP levels were observed (106 to >35,000 pg/ml). There was no difference in median NT-proBNP levels between patients with a cardiac and those with a noncardiac origin to their shock (3,046 pg/ml versus 2,959 pg/ml; P = 0.80), but an NT-proBNP value below 1,200 pg/ml had a negative predictive value of 92% for cardiogenic shock. NT-proBNP levels did not correlate with filling pressures or hemodynamics (findings not significant). NT-proBNP concentrations were higher in patients who died in the ICU (11,859 versus 2,534 pg/ml; P = 0.03), and the mortality rate of patients in the highest log-quartile of NT-proBNP (66.7%) was significantly higher than those in other log-quartiles (P < 0.001); NT-proBNP independently predicted ICU mortality (odds ratio 14.8, 95% confidence interval 1.8–125.2; P = 0.013), and was superior to Acute Physiology and Chronic Health Evaluation II score and brain natriuretic peptide in this regard.
Elevated levels of NT-proBNP do not necessarily correlate with high filling pressures among patients with ICU shock, but marked elevation in NT-proBNP is strongly associated with ICU death. Low NT-proBNP values in patients with ICU shock identifed those at lower risk for death, and may be useful in excluding the need for pulmonary artery catheter placement in such patients.
In the elderly the diagnosis of chronic heart failure is often challenging and the availability of echocardiography can be limited. Plasma levels of NT-proBNP are valuable tools to diagnose patients with heart failure. However, the performance of this biomarker to detect cardiac abnormalities in the very elderly remains unclear. The aims of this study were to investigate the relation between NT-proBNP and cardiac abnormalities and to evaluate the use of NT-proBNP to exclude structural and functional cardiac abnormalities in a community-based sample of "well-functioning" nonagenarians.
A diagnostic cross-sectional study embedded within the Leiden 85-plus Study in the municipality of Leiden, the Netherlands. Plasma NT-proBNP levels were measured and 2-dimensional echocardiography was performed in a subgroup of 80 well-functioning nonagenarians. Linear regression analysis was used to explore the relation between NT-proBNP and cardiac abnormalities and ROC curve analysis was used to assess the performance of NT-proBNP to exclude cardiac abnormalities. The upper limit of the lowest tertile of NT-proBNP was used as a cut-off value.
NT-proBNP levels were associated with abnormal left ventricular (LV) dimensions, LV systolic and diastolic function, left atrial enlargement and valvular heart disease. LV mass, E/A ratio and degree of aortic regurgitation were identified as independent predictors of NT-proBNP. NT-proBNP levels were higher with greater number of echocardiographic abnormalities (P < 0.001). A cut-off level of 269.5 pg/mL identified patients with abnormal LV dimensions or depressed LV systolic function (sensitivity 85%, negative predictive value (NPV) 77%, area under the curve 0.75 (95% CI 0.64-0.85)). In addition, high NPV were found for LV systolic dysfunction, left atrial enlargement, severe valvular heart disease and pulmonary hypertension. The test performance of NT-proBNP to exclude any echocardiographic abnormality showed a sensitivity of 82% and a NPV of 65%.
In this convenience sample of well-functioning nonagenarians NT-proBNP was related to a wide variety of functional and structural echocardiographic abnormalities. Moreover, NT-proBNP could be used to exclude echocardiographic abnormalities in well-functioning nonagenarians and might be used to indicate who needs to be referred for further cardiovascular examination.
This study was conducted to research the prognostic utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP), compare the utility of the Seattle Heart Failure Score (SHFS) with NT-proBNP, develop a risk-evaluation model based on NT-proBNP, assess the associations of NT-proBNP with patient characteristics, and screen for decisive factors of NT-proBNP in Chinese elderly with chronic heart failure (CHF).
Patients and methods
There were 306 patients (≥60 years) with CHF chosen as study subjects. Each one received an assessment of NT-proBNP on serum. The end point was all-cause mortality during a mean follow-up period of 471 days.
Subjects had a median age of 85 (60–100) years, a median NT-proBNP of 1,743.4 pg/mL, and a median SHFS of 1.87. During the follow-up period, 104 deaths occurred. NT-proBNP was significantly related to mortality (odds ratio 1.603, 95% confidence interval 1.407–1.826; P<0.001) and the significance persisted after full adjustment (odds ratio 1.282, 95% confidence interval 1.103–1.489; P=0.001). Age, New York Heart Association class IV CHF, plasma albumin, and neutrophils/lymphocytes were also independent predictors for mortality (P<0.05 for all). NT-proBNP and the SHFS showed similar predictive capacities (0.736 versus 0.796, P=0.105). The addition of NT-proBNP to the SHFS (0.818 versus 0.796, P=0.168) generated marginal growth in the c-statistic. The model based on NT-proBNP consisting of all selected predictors in this study, including age, New York Heart Association class IV CHF, plasma albumin, neutrophils/lymphocytes, and NT-proBNP, had a moderately higher c-statistic compared with the SHFS (0.846 versus 0.796, P=0.066). NT-proBNP was bound with the SHFS (r=0.500, P<0.001). Characteristics regarding general condition, inflammation, and cardiac and renal function were the decisive factors of NT-proBNP (P<0.05 for all).
As a comprehensive representation of the patient characteristics described earlier, NT-proBNP values provided significant prognostic power similar to the SHFS in Chinese elderly with CHF. A novel model based on NT-proBNP could offer help for risk stratification.
NT-proBNP; prognosis; chronic heart failure; elderly
Monitoring treatment efficacy and assessing outcome by serial measurements of natriuretic peptides in acute decompensated heart failure (ADHF) patients may help to improve outcome.
This was a prospective multi-center study of 171 consecutive patients (mean age 80 73-85 years) presenting to the emergency department with ADHF. Measurement of BNP and NT-proBNP was performed at presentation, 24 hours, 48 hours and at discharge. The primary endpoint was one-year all-cause mortality; secondary endpoints were 30-days all-cause mortality and one-year heart failure (HF) readmission.
During one-year follow-up, a total of 60 (35%) patients died. BNP and NT-proBNP levels were higher in non-survivors at all time points (all P < 0.001). In survivors, treatment reduced BNP and NT-proBNP levels by more than 50% (P < 0.001), while in non-survivors treatment did not lower BNP and NT-proBNP levels. The area under the ROC curve (AUC) for the prediction of one-year mortality increased during the course of hospitalization for BNP (AUC presentation: 0.67; AUC 24 h: 0.77; AUC 48 h: 0.78; AUC discharge: 0.78) and NT-proBNP (AUC presentation: 0.67; AUC 24 h: 0.73; AUC 48 h: 0.75; AUC discharge: 0.77). In multivariate analysis, BNP at 24 h (1.02 [1.01-1.04], P = 0.003), 48 h (1.04 [1.02-1.06], P < 0.001) and discharge (1.02 [1.01-1.03], P < 0.001) independently predicted one-year mortality, while only pre-discharge NT-proBNP was predictive (1.07 [1.01-1.13], P = 0.016). Comparable results could be obtained for the secondary endpoint 30-days mortality but not for one-year HF readmissions.
BNP and NT-proBNP reliably predict one-year mortality in patients with ADHF. Prognostic accuracy of both biomarker increases during the course of hospitalization. In survivors BNP levels decline more rapidly than NT-proBNP levels and thus seem to allow earlier assessment of treatment efficacy. Ability to predict one-year HF readmission was poor for BNP and NT-proBNP.
ClinicalTrials.gov identifier: NCT00514384.
Background and Objective
Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.
NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.
One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001).
Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings.
Background and Objectives
Several recent studies have shown that there is an inverse relationship between plasma B-type natriuretic peptide (BNP) and body mass index (BMI) in subjects with and without heart failure. Obesity frequently coexists with diabetes, so it is important to consider the relationship between diabetes and natriuretic peptide levels. We evaluated the influence of diabetes on the correlation of BNP and BMI.
Subjects and Methods
We examined 933 patients with chest pain and/or dyspnea undergoing cardiac catheterization between Feb. 2006 and Nov. 2007 in the Maryknoll cardiac center who had creatinine levels <2.0 mg/dL and normal systolic heart function. BMI was checked, transthoracic echocardiography was performed, and aminoterminal pro-brain natriuretic peptide (NT-proBNP) was sampled at the start of each case.
In 733 non-diabetic patients, mean plasma NT-proBNP levels of non obese individuals (BMI <23 kg/m2), overweight individuals (23≤ BMI <25 kg/m2), and obese individuals (BMI ≥25 kg/m2) showed a significant negative correlation with increasing BMI (856.39±237.3 pg/mL, 601.69±159.6 pg/mL, 289.62±164.9 pg/mL, respectively, p<0.0001). However, in 200 diabetic patients, the correlation between BMI and NT-proBNP was not significant (r=-0.21, p=0.19), and NT-proBNP did not correlate with mitral E/Ea in obese diabetic patients (r=0.14, p=0.56). NT-proBNP was significantly correlated with mitral E/Ea in the non-obese (r=0.24, p=0.008) and non diabetic (r=0.32, p=0.003) groups. Left ventricular (LV) mass index was significantly correlated with NT-proBNP in all BMI groups (r=0.61, p<0.001), and patients with concentric cardiac hypertrophy showed the highest NT-proBNP levels.
The present study demonstrates that obese patients have reduced concentrations of NT-proBNP compared to non obese patients despite having higher LV filling pressures. However, NT-proBNP is not suppressed in obese patients with diabetes. This suggests that factors other than cardiac status affect NT-proBNP concentrations.
B-type natriuretic peptide; Body mass index; Obesity
Right ventricular dysfunction (RVD) in acute pulmonary embolism (APE) can be assessed with helical computerized tomography (CT) and transthoracic echocardiography (TTE). Signs of RVD and elevated natriuretic peptides like NT-proBNP and cardiac troponin (TnT) are associated with increased risk of mortality. However, the prognostic role of both initial diagnostic strategy and the use of NT-proBNP and TnT for screening for long-term probability of RVD remains unknown. The aim of the study was to determine the role of helical CT and NT-proBNP in detection of RVD in the acute phase. In addition, the value of NT-proBNP for ruling out RVD at long-term follow-up was assessed.
Sixty-three non-high risk APE patients were studied. RVD was assessed at admission in the emergency department by CT and TTE, and both NT-proBNP and TnT samples were taken. These, excepting CT, were repeated seven months later.
At admission RVD was detected by CT in 37 (59 %) patients. RVD in CT correlated strongly with RVD in TTE (p < 0.0001). NT-proBNP was elevated (≥ 350 ng/l) in 32 (86 %) patients with RVD but in only seven (27 %) patients without RVD (p < 0.0001). All the patients survived until the 7-month follow-up. TTE showed persistent RVD in 6 of 63 (10 %) patients who all had RVD in CT at admission. All of them had elevated NT-proBNP levels in the follow-up compared with 5 (9 %) of patients without RVD (p < 0.0001).
TTE does not confer further benefit when helical CT is used for screening for RVD in non-high risk APE. All the patients who were found to have RVD in TTE at seven months follow-up had had RVD in the acute phase CT as well. Thus, patients without RVD in diagnostic CT do not seem to require further routine follow-up to screen for RVD later. On the other hand, persistent RVD and thus need for TTE control can be ruled out by assessment of NT-proBNP at follow-up. A follow-up protocol based on these findings is suggested.
Non-high risk pulmonary embolism; Follow-up; right ventricular dysfunction; NT-pro-BNP; Echocardiography, helical CT; CT pulmonary angiography
Patients with acute respiratory distress syndrome suffer from profound cardiac and pulmonary derangement, including right ventricular strain and noncardiogenic pulmonary edema, which may potentially alter concentrations of cardiac natriuretic peptides. We sought to determine whether N-terminal probrain natriuretic peptide (NT-proBNP) levels are elevated in acute respiratory distress syndrome and whether they can serve as a marker of prognosis in this setting.
Tertiary-care academic medical center.
One hundred seventy-seven acute respiratory distress syndrome subjects enrolled in a prospective intensive care unit cohort.
Measurements and Main Results
NT-proBNP was measured from blood taken within 48 hrs of acute respiratory distress syndrome onset. Patients were followed for the primary outcome of 60-day mortality and secondary outcomes of organ dysfunction and ventilator-free days. Seventy patients died (40%). Median NT-proBNP level was 3181 ng/L (interquartile range 723–9246 ng/L). NT-proBNP levels were significantly higher among nonsurvivors (p < .0001). Receiver operating curve analysis revealed an optimal NT-proBNP cut-point of 6813 ng/L for predicting death. Patients with levels above the cut-point had significantly higher odds of mortality on multivariable analysis (odds ratio 2.36, 95% confidence interval 1.11– 4.99, p = .02) than those with levels below the cut-point. Kaplan-Meier survival analysis showed that this difference emerged early and was sustained (p < .0001). Patients with elevated NT-proBNP also had higher organ dysfunction scores (p < .0001) and fewer ventilator free days (p = .03) than those with lower NT-proBNP levels.
NT-proBNP levels are elevated among acute respiratory distress syndrome patients and parallel the severity of the syndrome and likelihood for morbidity and mortality. This demonstrates the potential utility of this biomarker for prognosis in this disease.
acute respiratory distress syndrome; prognosis; biological markers; N-terminal pro-BNP
The purpose of this study was to investigate circulating pro–B-type natriuretic peptide (proBNP1–108) in the general community and evaluate its ability to detect left ventricular (LV) dysfunction.
The current concept for cardiac endocrine function is that, in response to cardiac stress, the heart secretes B-type natriuretic peptide (BNP1–32) and amino-terminal pro–B-type natriuretic peptide (NT-proBNP1–76) after intracardiac cleavage of their molecular precursor, proBNP1–108. We hypothesized that proBNP1–108 circulates in normal human subjects and that it is a useful biomarker for LV dysfunction.
Our population-based study included a cohort of 1,939 adults (age >45 years) from Olmsted County, Minnesota, with 672 participants defined as healthy. Subjects underwent in-depth clinical characterization, detailed echocardiography, and measurement of proBNP1–108. Independent factors associated with proBNP1–108 and test characteristics for the detection of LV dysfunction were determined.
ProBNP1–108 in normal humans was strongly influenced by sex, age, heart rate, and body mass index. The median concentration was 20 ng/l with a mean proBNP1–108 to NT-proBNP1–76 ratio of 0.366, which decreased with heart failure stage. ProBNP1–108 was a sensitive (78.8%) and specific (86.1%) biomarker for detecting LV systolic dysfunction, which was comparable to BNP1–32, but less than NT-proBNP1–76, in several subsets of the population.
ProBNP1–108 circulates in the majority of healthy humans in the general population and is a sensitive and specific biomarker for the detection of systolic dysfunction. The proBNP1–108 to NT-proBNP1–76 ratio may provide insights into altered proBNP1–108 processing during heart failure progression. Thus, this highly specific assay for proBNP1–108 provides important new insights into the biology of the BNP system.
biomarker; BNP; heart failure; natriuretic peptide; NT-proBNP; proBNP
Increasing serum levels of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) are associated with worsening heart failure (HF) in adults. We determined whether changes in NT-proBNP level are associated with changes in symptoms and left ventricular (LV) systolic function and remodeling in children with HF secondary to dilated cardiomyopathy.
We retrospectively examined associations between serum NT-proBNP levels and NYHA/Ross functional class, LV systolic and diastolic diameter (LVSD-z and LVDD-z), LV ejection fraction (LVEF), and LV shortening fraction (LVSF-z) using generalized linear mixed models. Fluctuation in functional class of subjects was also modeled using logistic regression and receiver operating characteristic (ROC) curves.
In 36 children (14 males), a 10-fold increase in NT-proBNP serum levels was associated (P<0.001) with a 9.8% decrease in LVEF, a 3.25-unit drop in LVSF-z, a 1.53-unit increase in LVDD-z, a 2.64-unit increase in LVSD-z, and an increased odds of being in functional class III/IV (OR 85.5; 95% CI, 10.9 to 671.0). An NT-proBNP level greater than 1000 pg/mL identified children constantly or intermittently in functional class III-IV with 95% sensitivity and 80% specificity. The reliability of a single NT-proBNP value was 0.61, but the means for two and three NT-proBNP values were 0.76 and 0.82, respectively.
In children with HF, NT-proBNP is associated with cardiac symptoms and indices of LV systolic dysfunction and remodeling. NT-proBNP >1000 pg/mL identifies highly symptomatic children. Within subject serial measurements of NT-proBNP are needed for a reliable and accurate determination of disease status and/or course.
Most studies reported using N-terminal pro-brain natriuretic peptide (NT-proBNP) in diagnosis of heart failure but there is controversy about use of these tests in determining prognosis and classification of severity of heart failure. The objective of this study was to determine the value of plasma NT-proBNP levels assessment in evaluation of mortality and morbidity of patients with systolic left ventricular dysfunction.
A cohort study was performed in 150 patients with heart failure since September 2009 until February 2010. The patients were followed for 6 months to assess their prognosis. Patients were divided into two good and bad prognosis groups according to severity of heart failure in New York Heart Association (NYHA) class and frequency of hospital admission and mortality due to cardiac causes. Patients with good prognosis had ≥1 admission or no mortality or NYHA class ≥2 and patients that had one of this criteria considered as bad prognosis groups. Pro-BNP levels were measured at baseline and left ventricular ejection fraction (LVEF) was estimated with echocardiography. Data was analyzed with using Chi-square, t-test, ANOVA, Kruskal-Wallis tests.
In patients with heart failure that enrolled in this clinical study, ten patients were lost during follow-up. The mean of NT-proBNP is significantly correlated with ejection fraction (p=0.003) and NYHA class (p<0.001). In our study among 140 patients who were follow-up for 6 months, 11(9.7%) of individuals died with mean NT-proBNP of 8994.8±8375 pg/ml, in survived patients mean NT-proBNP was 3756.8±5645.6 pg/ml that was statistically significant (P=0.02). Mean NT-proBNP in the group with good prognosis was 2723.8±4845.2 pg/ml and in the group with bad prognosis was 5420.3±6681 pg/ml, difference was statistically significant (P=0.0001).
Our study in consistent with other studies confirms that NT-proBNP is significantly correlated with mortality and morbidity. This could be predicting adverse out come and stratification in patients with heart failure. It is recommended that more research be performed in Iran.
Heart failure; Pro-BNP; Prognosis; Mortality; Morbidity
The purpose of the research was to find out the factors which influence plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, then to assess whether preoperative plasma NT-proBNP levels could predict postoperative outcomes of cardiac surgery.
Between November 2008 and February 2010,225 patients who underwent cardiac surgery in our department were included in the study. The mean age was 61.25 ± 12.54 years, and 156 (69.3%) patients were male. NT-proBNP, CK-MB, cTnT and creatinine levels were measured preoperatively and 24 hours after operation. Postoperatively outcomes including ventilation time, length of stay in ICU and hospital, and mortality were closely monitored. The endpoints includes: 1) use of inotropic agents or intra-aortic balloon pump ≥24 h; 2) creatinine level elevated to hemodialysis; 3) cardiac events; 4) ICU stay ≥5d; 5) ventilation dependence ≥ 72 h; 6) deaths within 30 days of surgery.
NT-proBNP concentrations (median [interquartile range]) increased from 728.4 pg/ml (IQR 213.5 to 2551 pg/ml) preoperatively to 1940.5 pg/ml (IQR 995.9 to 3892 pg/ml) postoperatively (P = 0.015). Preoperative atrial fibrillation, NYHA class III/IV, ejection fraction, pulmonary arterial pressure, left ventricle end-diastolic diameter (LVEDD), preoperative plasma creatinine and cTnT levels were significantly associated with preoperative NT-proBNP levels in univariate analysis. The preoperative NT-proBNP was closely related to ventilation time (P = 0.009), length of stay in ICU (P = 0.004) and length of stay in hospital (P = 0.019). Receiver operating characteristic curves demonstrated a cut-off value above 2773.5 pg/ml was the best cutoff (sensitivity of 63.6% and specificity of 80.8%) to predict the mortality within 30d of surgery.
Preoperative plasma NT-proBNP level presents a high individual variability in patients undergoing cardiac surgery. NYHA classification, ejection fraction, pulmonary arterial pressure, LVEDD, atrial fibrillation, preoperative plasma creatinine, and cTnT levels are significantly associated with preoperative NT-proBNP levels. Preoperative NT-proBNP is a valuable marker in predicting postoperative outcomes.
N-terminal pro-brain natriuretic peptide; Cardiac surgery; Prognosis
Objective: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a diagnostic and prognostic marker for systolic heart failure in the general population.
Design: Study participants, randomly selected to be representative of the background population, filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, electrocardiography, echocardiography, and blood sampling and were followed up for a median (range) period of 805 (60−1171) days.
Setting: Participants were recruited from four randomly selected general practitioners and were examined in a Copenhagen university hospital.
Patients: 382 women and 290 men in four age groups (50−59 (n = 174); 60−69 (n = 204); 70−79 (n = 174); ⩾ 80 years (n = 120)).
Main outcome measures: Value of NT-proBNP in evaluating patients with symptoms of heart failure and impaired left ventricular (LV) systolic function; prognostic value of NT-proBNP for mortality and hospital admissions.
Results: In 38 (5.6%) participants LV ejection fraction (LVEF) was ⩽ 40%. NT-proBNP identified patients with symptoms of heart failure and LVEF ⩽ 40% with a sensitivity of 0.92, a specificity of 0.86, positive and negative predictive values of 0.11 and 1.00, and area under the curve of 0.94. NT-proBNP was the strongest independent predictor of mortality (hazard ratio (HR) = 5.70, p < 0.0001), hospital admissions for heart failure (HR = 13.83, p < 0.0001), and other cardiac admissions (HR = 3.69, p < 0.0001). Mortality (26 v 6, p = 0.0003), heart failure admissions (18 v 2, p = 0.0002), and admissions for other cardiac causes (44 v 13, p < 0.0001) were significantly higher in patients with NT-proBNP above the study median (32.5 pmol/l).
Conclusions: Measurement of NT-proBNP may be useful as a screening tool for systolic heart failure in the general population.
N-terminal pro-brain natriuretic peptide; diagnostic techniques; ejection fraction; heart failure; population study; prognosis
We compared the diagnostic accuracy of N-terminal prohormone brain natriuretic peptide (NT-proBNP) with that of echocardiography in the evaluation of left ventricular diastolic dysfunction after coronary artery bypass grafting.
Thirty patients were studied prospectively. Patients who had recent myocardial infarction, unstable angina pectoris, or low ejection fraction with systolic dysfunction were excluded. Two blood samples were obtained: before anesthetic induction and on the 7th postoperative day. Levels of NT-proBNP were measured by electrochemiluminescence immunoassay. Comprehensive echocardiographic Doppler examinations were performed on admission and on the 7th postoperative day. Relationships between NT-proBNP levels and echocardiographic indices were evaluated by correlation, multiple linear regression, and receiver-operating characteristic curve analysis.
There were significant and correlated worsenings in diastolic stage as determined both by echocardiographic indices and NT-proBNP levels. Early transmitral-to-early diastolic annular velocity ratio (E/Ea) was found to correlate with both NT-proBNP and postoperative diastolic functional stage (r=0.78, P <0.001). Mitral E/Ea was significantly more sensitive than were NT-proBNP levels in predicting diastolic functional stage. The area under the receiver-operating characteristic curve for NT-proBNP was significantly lower than that of mitral E/Ea (mean difference, 0.12; P=0.024). The NT-proBNP had 87.5% sensitivity and 55% specificity, whereas E/Ea had 87.5% sensitivity and 86.4% specificity.
Plasma NT-proBNP levels are significantly related to mitral E/Ea ratio, which is a predictor of diastolic stage. Therefore, elevated NT-proBNP levels may indicate the time for a Doppler echocardiographic evaluation and identify a subgroup of patients at high risk who need closer monitoring during the early postoperative period.
Diastole/physiology; echocardiography; heart ventricles; left ventricular dysfunction; myocardial ischemia/diagnosis; natriuretic peptide, brain/blood/diagnostic use; predictive value of tests; pro-brain natriuretic peptide; sensitivity and specificity; ventricular dysfunction, left/blood/diagnosis/physiology
While natriuretic peptides have demonstrated diagnostic and prognostic potential in cardiac disorders, little is known about their relationship with the onset and quantification of myocardial infarction. The relationship of serial N-terminal pro-brain natriuretic peptide (NT-proBNP) with duration from symptom onset, infarct size and prognosis in ST elevation myocardial infarction (STEMI) patients treated with primary percutaneous intervention was examined.
METHODS AND RESULTS
Three hundred thirty-one STEMI patients in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial, which evaluated pexelizumab versus placebo, were studied. NT-proBNP (pg/mL) was measured at randomization, 24 h and 72 h; creatine kinase-MB area under the curve was measured at 72 h; and QRS score was assessed at discharge. Prognosis was ascertained from the 90-day composite clinical outcome of death, shock, stroke and congestive heart failure. Multivariate logistical regression was used to adjust for baseline characteristics for models at randomization, 24 h and 72 h. NT-proBNP was higher in patients with longer time from symptom onset (P<0.001) and correlated with measures of infarct size, including the area under the curve (P<0.001) and QRS score (P<0.001). Patients reaching the primary end point had markedly higher NT-proBNP at each sampling period (P<0.001). NT-proBNP at all time points was the strongest independent predictor of the primary end point in the multivariate model: in the 24 h model, only age and 24 h NT-proBNP (C-index 0.83); and only age, Killip class and NT-proBNP was in the 72 h model (C-index 0.85).
Higher NT-proBNP at 24 h correlated with larger infarct size and worse clinical outcomes. NT-proBNP at baseline, 24 h and 72 h after presentation with acute STEMI, is an independent predictor of a poor outcome and adds clinically useful prognostic information.
Clinical trial; Myocardial infarction; Natriuretic peptides
NT-proBNP has been widely regarded as a useful tool for diagnosis or exclusion of heart failure (HF) in many settings. However, in patients with acute exacerbation of chronic bronchitis (AECB), its roles have not been well described. The objective of this study was to evaluate the diagnostic performance of NT-proBNP for identifying left ventricular (LV) failure in such patients.
Methods and Results
311 AECB patients and 102 stable chronic bronchitis patients with no history of HF were enrolled. Plasma NT-proBNP concentrations were measured using Roche Elecsys. The European Society of Cardiology (ESC) diagnostic principles were adopted to identify HF and the diagnostic performance of NT-proBNP was evaluated by ROC. Our results showed, the median NT-proBNP level in patients with LV failure [4828.4 (2044.4–9203.6) ng/L] was significantly higher than that in those without LV failure [519.2 (179.1–1409.8) ng/L, p<0.001] and stable controls [207.5 (186.5–318.2) ng/L, p<0.001]. LV failure, renal function, atrial fibrillation and systolic pulmonary artery pressure were independent predictors of NT-proBNP levels (all p<0.05). The area under ROC curve (AUC) of NT-proBNP for identifying LV failure was 0.884, significantly superior to clinical judgment alone (AUC 0.835, p = 0.0294). At the optimal cutoff value of 935.0 ng/L, NT-proBNP yielded sensitivity 94.4%, specificity 68.2%, accuracy 74.3% and negative predictive value 97.6%. Adding the results of NT-proBNP to those of clinical judgment improved the diagnostic accuracy for LV failure.
As a tool for diagnosis or exclusion of HF, NT-proBNP can help physicians identify LV failure in patients with AECB.
This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample.
Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample.
Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age ≥ 45 years) of Olmsted County, Minnesota.
In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction ≤ 40% or ≤ 50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction ≤ 40% or ≤ 50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone.
Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.
The overall prognosis of critically ill patients with cancer has improved during the past decade. The aim of this study was to identify early prognostic factors of intensive care unit (ICU) mortality in patients with cancer.
We designed a prospective, consecutive, observational study over a one-year period. Fifty-one cancer patients with septic shock were enrolled.
The ICU mortality rate was 51% (26 deaths). Among the 45 patients who benefited from transthoracic echocardiography evaluation, 17 showed right ventricular dysfunction, 18 showed left ventricular diastolic dysfunction, 18 showed left ventricular systolic dysfunction, and 11 did not show any cardiac dysfunction. During the first three days of ICU course, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly higher in patients presenting cardiac dysfunctions compared to patients without any cardiac dysfunction. Multivariate analysis discriminated early prognostic factors (within the first 24 hours after the septic shock diagnosis). ICU mortality was independently associated with NT-proBNP levels at day 2 (odds ratio, 1.2; 95% confidence interval, 1.004 to 1.32; p = 0.022). An NT-proBNP level of more than 6,624 pg/ml predicted ICU mortality with a sensitivity of 86%, a specificity of 77%, a positive predictive value of 79%, a negative predictive value of 85%, and an accuracy of 81%.
We observed that critically ill cancer patients with septic shock have an approximately 50% chance of survival to ICU discharge. NT-proBNP was independently associated with ICU mortality within the first 24 hours. NT-proBNP could be a useful tool for detecting high-risk cancer patients within the first 24 hours after septic shock diagnosis.
Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test.
NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH.
NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH.
We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.
Cardiac dysfunction is common in acute respiratory diseases and may influence prognosis. We hypothesised that blood levels of N-terminal B-type natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T would predict mortality in adults with community-acquired pneumonia.
Methods and Findings
A prospective cohort of 474 consecutive patients admitted with community-acquired pneumonia to two New Zealand hospitals over one year. Blood taken on admission was available for 453 patients and was analysed for NT-proBNP and Troponin T. Elevated levels of NT-proBNP (>220 pmol/L) were present in 148 (33%) and 86 (19%) of these patients respectively. Among the 26 patients who died within 30 days of admission, 23 (89%) had a raised NT-proBNP and 14 (53%) had a raised Troponin T level on admission compared to 125 (29%) and 72 (17%) of the 427 who survived (p values<0.001). Both NT-proBNP and Troponin T predicted 30-day mortality in age-adjusted analysis but after mutual adjustment for the other cardiac biomarker and the Pneumonia Severity Index, a raised N-terminal pro-brain natriuretic peptide remained a predictor of 30-day mortality (OR = 5.3, 95% CI 1.4–19.8, p = 0.013) but Troponin T did not (OR = 1.3, 95% CI 0.5–3.2, p = 0.630). The areas under the receiver-operating curves to predict 30-day mortality were similar for NT-proBNP (0.88) and the Pneumonia Severity Index (0.87).
Elevated N-terminal B-type natriuretic peptide is a strong predictor of mortality from community-acquired pneumonia independent of clinical prognostic indicators. The pathophysiological basis for this is unknown but suggests that cardiac involvement may be an under-recognised determinant of outcome in pneumonia and may require a different approach to treatment. In the meantime, measurement of B-type natriuretic peptides may help to assess prognosis.