N-terminal pro brain natriuretic peptide (NT-proBNP) is a cardiac biomarker that has recently shown to be of diagnostic value in a diagnosis of decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch. We sought to study whether sepsis-induced myocardial dilation would result in an elevation of NT-proBNP.
Serum NT-proBNP measurements were made in six consecutive patients with septic shock within 6 hours of admission to the intensive care unit.
Markedly elevated levels of NT-proBNP were found in all six patients.
NT-proBNP levels can be markedly elevated in critically ill patients presenting with septic shock. An elevated NT-proBNP level in a critically ill patient is not specific for decompensated heart failure.
brain natriuretic peptide; N-terminal pro brain natriuretic peptide; septic shock
B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) are promising cardiac biomarkers that have recently been shown to be of diagnostic value in decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch and volume overload. In view of the high prevalence of cardiac disorders in the intensive care unit, the experience of elevated natriuretic peptide levels in the critically ill might be of enormous diagnostic and therapeutic value. BNP and NT-proBNP levels rise to different degrees in critical illness and may also serve as markers of severity and prognosis in diseases beyond acute or chronic heart failure. The diagnostic and prognostic use of natriuretic peptides in the intensive care setting for patients with various forms of shock could be an attractive alternative as noninvasive markers of cardiac dysfunction that could obviate the need for pulmonary artery catheterization in some patients.
B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) plasma levels are commonly high at the early phase of septic shock and have been suggested to be prognostic markers for this condition. It is uncertain, however, whether this increase reflects sepsis related cardiac dysfunction. In a recent issue of Critical Care, Mokart and coworkers showed the accuracy of NT-proBNP in predicting intensive care unit mortality in cancer patients with septic shock, which could help in identifying high risk cancer patients. Results from repeated transthoracic echocardiographs show that NT-proBNP on day 2 after admission was higher in patients presenting with cardiac dysfunction, whereas NT-proBNP on day 1 did not predict cardiac dysfunction. These data suggest that after an initial overexpression of NT-proBNP in all septic patients, patients with cardiac dysfunction will present persistent high levels of NT-proBNP.
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.
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.
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.
Cardiomyopathy is reported in Duchenne and Becker muscle dystrophy patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone produced mainly by ventricular cardiomyocytes and its production is up regulated in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has been shown to be a robust laboratory parameter to diagnose and monitor cardiac failure, and it may be helpful to screen for asymptomatic left ventricular dysfunction. Therefore we tested whether NT-proBNP can distinguish patients with Duchenne or Becker muscular dystrophy patients and carriers of a dystrophin mutation with a dilated cardiomyopathy from those without.
In a cohort of Duchenne and Becker muscle dystrophy patients (n = 143) and carriers (n = 219) NT-proBNP was measured, and echocardiography was performed to diagnose dilated cardiomyopathy (DCM).
In total sixty-one patients (17%) fulfilled the criteria for DCM, whereas 283 patients (78%) had an elevated NT-pro BNP. The sensitivity of NT-proBNP for DCM in patients or carriers was 85%, the specificity 23%, area under the ROC-curve = 0.56. In the specified subgroups there was also no association.
Measurement of NT-pro BNP in patients suffering from Duchenne or Becker muscular dystrophy and carriers does not distinguish between those with and without dilated cardiomyopathy.
Duchenne muscular dystrophy; Becker muscular dystrophy; Brain Natriuretic peptide; Dystrophinopathy carriers; Dilated cardiomyopathy
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.
The N-terminal fragment of pro-brain type natriuretic peptide (NT-proBNP) is an established biomarker for cardiac failure.
To determine the influence of preoperative serum NT-proBNP on postoperative outcome and mid-term survival in patients undergoing coronary artery bypass grafting (CABG).
In 819 patients undergoing isolated CABG surgery preoperative serum NT-proBNP levels were measured. NT-proBNP was correlated with various postoperative outcome parameters and survival rate after a median follow-up time of 18 (0.5–44) months. Risk factors of mortality were identified using χ2, Mann–Whitney test, and Cox regression.
NT-proBNP levels >430 ng/ml and >502 ng/ml predicted hospital and overall mortality (p<0.05), with an incidence of 1.6% and 4%, respectively. Kaplan–Meier analysis revealed decreased survival rates in patients with NT-proBNP >502 ng/ml (p = 0.001). Age, preoperative serum creatinine, diabetes, chronic obstructive pulmonary disease, low left ventricular ejection fraction and BNP levels >502 ng/ml were isolated as risk factors for overall mortality. Multivariate Cox regression analysis, including the known factors influencing NT-proBNP levels, identified NT-proBNP as an independent risk factor for mortality (OR = 3.079 (CI = 1.149-8.247), p = 0.025). Preoperative NT-proBNP levels >502 ng/ml were associated with increased ventilation time (p = 0.005), longer intensive care unit stay (p = 0.001), higher incidence of postoperative hemofiltration (p = 0.001), use of intra-aortic balloon pump (p<0.001), and postoperative atrial fibrillation (p = 0.031)
Preoperative NT-proBNP levels >502 ng/ml predict mid-term mortality after isolated CABG and are associated with significantly higher hospital mortality and perioperative complications.
Brain type natriuretic peptide; BNP; NT-proBNP; CABG; Coronary artery disease
Objective: To compare head to head the diagnostic accuracy of B type natriuretic peptide (BNP) and the amino terminal fragment of its precursor hormone (NT-proBNP) for congestive heart failure (CHF) in an emergency setting.
Methods: 251 consecutive patients presenting to the emergency department with dyspnoea as a chief complaint were prospectively studied. Patients with acute coronary syndromes were excluded. The diagnosis of CHF was based on the Framingham score for CHF plus echocardiographic evidence of systolic or diastolic dysfunction. Blood concentrations of BNP and NT-proBNP were measured by two commercially available assays (Abbott and Roche methods). The diagnostic accuracies of BNP and NT-proBNP were assessed by receiver operating characteristic curve analysis.
Results: Areas under the curve for BNP and NT-proBNP in patients with dyspnoea caused by CHF (n = 137) and in patients with dyspnoea attributable to other reasons (n = 114) did not differ significantly (area under the curve 0.916 v 0.903, p = 0.277, statistical power 94%). Cut off concentrations with the highest diagnostic accuracy were 295 ng/l for BNP (sensitivity 80%, specificity 86%, diagnostic accuracy 83%) and 825 ng/l for NT-proBNP (sensitivity 87%, specificity 81%, diagnostic accuracy 84%). Evaluation of discordant false classifications at these cut off concentrations showed no advantage for either BNP nor NT-proBNP in the biochemical diagnosis of CHF (17 misclassifications by BNP and 14 by NT-proBNP, p = 0.720). In the population studied, age, sex, and renal function had no impact on the diagnostic utility of both tests when compared by logistic regression models.
Conclusions: BNP and NT-proBNP may be equally useful as an aid in the diagnosis of CHF in short of breath patients presenting to the emergency department.
diagnosis; echocardiography; heart failure; natriuretic peptides
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.
Echocardiographic indices of cardiac structure and function and natriuretic peptide levels are strong predictors of mortality in patients with heart failure. Whether cardiac ultrasound and natriuretic peptides provide independent prognostic information is uncertain.
Echocardiograms and measurements of N-terminal pro-B type natriuretic peptide (NT-proBNP) were prospectively performed in 211 patients with left ventricular systolic dysfunction who were followed for a median of 4 years. Echocardiographic variables and NT-proBNP were examined as predictors of all-cause mortality in univariable and multivariable proportional hazards models.
Participants averaged 57 (SD 12) years of age and had a mean left ventricular ejection fraction of 32 (SD 11) %. A total of 71 patients (34%) died during the follow-up period. NT-ProBNP was a strong predictor of mortality (P < 0.001) as were multiple echocardiographic measures. In models that included age and NT-proBNP, with other clinical variables eligible for entry by stepwise selection, significant predictors of death included left ventricular ejection fraction (P = 0.013) and end-diastolic volume (P < 0.001), left atrial volume index (P = 0.005), right atrial volume index (P = 0.003), and tricuspid regurgitation area (P = 0.015). In models that also included left ventricular ejection fraction, end-diastolic volume of the left ventricle (P = 0.019), left atrial volume (P = 0.026), and right atrial volume (P = 0.020) remained significant predictors of mortality.
Left ventricular size and function and left atrial and right atrial sizes are significant predictors of all-cause mortality in patients with heart failure, independent of NT-proBNP levels and other clinical variables.
Atrial fibrillation (AF) is the most common cardiac arrhythmia with a population prevalence of about 1%. Natriuretic peptide level is elevated in patients with AF with diastolic dysfunction even with a normal left ventricular (LV) ejection fraction. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level and Doppler echocardiographic parameters for diastolic function have shown correlation with LV filling pressures. We aimed to evaluate the relationship between echocardiographic parameters and serum NT-proBNP in patients with AF with preserved LV ejection fraction.
We examined transthoracic echocardiography and NT-proBNP levels in the patients with AF and patients with sinus rhythm. Blood samples were taken for serum NT-proBNP measurements within 24 hours of echocardiographic examination. The group 1 was the patients with sinus rhythm (n = 30, mean age 68 ± 13 years) and the group 2 was the patients with AF (n = 33, mean age 70 ± 14 years).
The group 2 patients had significantly higher mitral E, E' (lateral annulus), E/E' (septal annulus), left atrial (LA) volume index, LA size, pulmonary vein diastolic velocity, and NT-proBNP level than those of group 1 patients (p < 0.05). The area under the receiver-operating characteristic curve showed a NT-proBNP had good diagnostic power for E/E' (septal annulus) > 15 in patients with AF at cutoff value of 433 pg/mL.
NT-proBNP level is well correlated with Doppler echocardiographic parameters of diastolic function in patients with AF and preserved LV ejection fraction. NT-proBNP level more than 433 pg/mL may suggest elevated LV filling pressure in patients with AF.
Atrial fibrillation; NT-proBNP; Doppler echocardiography
To assess the long‐term prognostic value of plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) after major vascular surgery.
A single‐centre prospective cohort study.
335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery.
Prior to surgery, baseline NT‐proBNP level was measured. Patients were also evaluated for cardiac risk factors according to the Revised Cardiac Risk Index. Dobutamine stress echocardiography (DSE) was performed to detect stress‐induced myocardial ischaemia.
Main outcome measures
The prognostic value of NT‐proBNP was evaluated for the endpoints all‐cause mortality and major adverse cardiac events (MACE) during long‐term follow‐up.
In this patient cohort (mean age: 62 years, 76% male), median NT‐proBNP level was 186 ng/l (interquartile range: 65–444 ng/l). During a mean follow‐up of 14 (SD 6) months, 49 patients (15%) died and 50 (15%) experienced a MACE. Using receiver operating characteristic curve analysis for 6‐month mortality and MACE, NT‐proBNP had the greatest area under the curve compared with cardiac risk score and DSE. In addition, an NT‐proBNP level of 319 ng/l was identified as the optimal cut‐off value to predict 6‐month mortality and MACE. After adjustment for age, cardiac risk score, DSE results and cardioprotective medication, NT‐proBNP ⩾319 ng/l was associated with a hazard ratio of 4.0 for all‐cause mortality (95% CI: 1.8 to 8.9) and with a hazard ratio of 10.9 for MACE (95% CI: 4.1 to 27.9).
Preoperative NT‐proBNP level is a strong predictor of long‐term mortality and major adverse cardiac events after major non‐cardiac vascular surgery.
dobutamine stress echocardiography; natriuretic peptides; prognosis; vascular surgery
Although the cardiac biomarker troponin T (cTnT) is strongly related to mortality in end-stage renal disease, the independent association of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cTnT in predicting outcomes is unknown.
To determine factors associated with NT-proBNP and cTnT, and to determine whether these levels are associated with mortality.
Settings and Participants:
Asymptomatic hemodialysis patients (n=150) in 4 university-affiliated hemodialysis units.
Exposure and Outcomes:
For cross-sectional analysis, echocardiographic variables as exposures and N-terminal proBNP and cardiac troponin T as outcomes; for longitudinal analysis, association of N-terminal proBNP and cardiac troponin T as exposures to all-cause and cardiovascular disease mortality as outcomes.
In a multivariate regression analysis, low midwall fractional shortening a measure of poor systolic function was an independent correlate of log NT-proBNP (p<0.01), while left ventricular mass index was an independent correlate of cTnT (p<0.01). Over a median follow-up of 24 months, 46 patients died of which, 26 died due to cardiovascular causes. NT-ProBNP had a strong graded relationship with all-cause (Hazard Ratio (HR) 1.54, 4.78 and 4.03 for increasing quartiles, Chi2 32.2, p<0.001) and cardiovascular mortality (HR 2.99, 10.95, 8.54 Chi2 23.66, p<0.01), while cTnT had a weaker relationship with all-cause (HR 1.57, 2.32, 3.39, Chi2 23.09, p<0.01) and cardiovascular mortality (HR 1, 0.81, 2.12, 2.14, Chi2 15.05, p=0.1). The combination of the two biomarkers did not improve the association with all-cause or cardiovascular mortality compared to NT-proBNP alone. NT-proBNP was a marker of mortality even after adjusting for left ventricular mass index and midwall fractional shortening.
Our cohort was predominantly black and of limited sample size.
NT-proBNP strongly correlates with left ventricular systolic dysfunction and is more strongly associated with mortality than cTnT in asymptomatic hemodialysis patients.
NT-proBNP; Troponin T; left ventricular mass; left ventricular function; mortality; hemodialysis
Plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide useful prognostic predictors in patients after cardiac surgery. However, predictive accuracy of NT-proBNP levels has varied significantly according to renal dysfunction. The purpose of this study was to assess whether preoperative NT-proBNP levels could be used as predictors of early postoperative outcomes on the basis of renal function in patients undergoing off-pump coronary artery bypass surgery (OPCAB).
In 219 patients undergoing elective OPCAB, NT-proBNP and an estimated glomerular filtration rate (eGFR) were assessed preoperatively. All patients were divided into 3 groups according to tertiles of eGFR: the first (eGFR ≥ 90 ml/min/1.73 m2), the second (90 ml/min/1.73 m2 > eGFR ≥ 72 ml/min/1.73 m2) and the third tertile group (eGFR < 72 ml/min/1.73 m2). End point was the composite of early postoperative complications defined as myocardial infarction, new onset atrial fibrillation, ventricular dysfunction, prolonged mechanical ventilator care (> 48 hr), prolonged ICU stay (≥ 3 days), and in hospital mortality.
There was no difference in early postoperative complications among groups. A preoperative NT-proBNP level of 228 pg/ml and 302 pg/ml (sensitivity 70%, specificity 67%, P < 0.001 and sensitivity 73%, specificity 63%, P = 0.001, respectively) were optimal cut-off values predicting complicated early postoperative course in second and third tertile group, respectively.
Preoperative NT-proBNP levels seem to be predictive of early postoperative complications in patients with eGFR < 90 ml/min/1.73 m2 undergoing OPCAB.
NT-proBNP; OPCAB; Renal function
Cross-sectional studies have shown that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are predictive of cardiovascular death in haemodialysis (HD) patients. In the present study, we tested the hypothesis that monitoring NT-proBNP measurements adds further prognostic information, i.e. predicts congestive heart failure (CHF) events.
In a prospective cohort of 236 HD patients, NT-proBNP levels were measured monthly during 18 months. Patients were divided according to the occurrence of CHF events. In a nested case-control study, we assessed the evolution of NT-proBNP levels.
On average, the 236 HD patients were followed up for 12.5 months, a period during which 44 patients developed a CHF event (half requiring hospitalisation). At baseline, patients who developed a CHF event had significantly more dilated cardiomyopathy and/or altered left ventricular ejection fraction and higher NT-proBNP levels compared with patients who did not develop a CHF event. During follow-up, we observed a significant increase in NT-proBNP levels preceding the CHF event. At a 20% relative increase of NT-proBNP, the sensitivity of NT-proBNP as a predictor of CHF events was 0.57 and the specificity 0.77.
The relative change in NT-proBNP levels is a significant risk predictor of a CHF event.
Congestive heart failure; Haemodialysis; NT-proBNP; Monitoring; Risk predictor
Serum levels of N–terminal proB–type natriuretic peptide (NT–proBNP) are elevated in patients acute respiratory distress syndrome (ARDS). Recent studies showed a lower incidence of acute cor pulmonale in ARDS patients ventilated with lower tidal volumes. Consequently, serum levels of NT–proBNP may be lower in these patients.
We investigated the relation between serum levels of NT–proBNP and tidal volumes in critically ill patients without ARDS at the onset of mechanical ventilation.
Secondary analysis of a randomized controlled trial of lower versus conventional tidal volumes in patients without ARDS. NT–pro BNP were measured in stored serum samples. Serial serum levels of NT–pro BNP were analyzed controlling for acute kidney injury, cumulative fluid balance and presence of brain injury. The primary outcome was the effect of tidal volume size on serum levels of NT–proBNP. Secondary outcome was the association with development of ARDS.
Samples from 150 patients were analyzed. No relation was found between serum levels of NT–pro BNP and tidal volume size. However, NT-proBNP levels were increasing in patients who developed ARDS. In addition, higher levels were observed in patients with acute kidney injury, and in patients with a more positive cumulative fluid balance.
Serum levels of NT–proBNP are independent of tidal volume size, but are increasing in patients who develop ARDS.
Mechanical ventilation; Acute lung injury; Tidal volume; Ventilator–associated lung injury; NT–proBNP
Recent studies have shown that in addition to brain (or B-type) natriuretic peptide (BNP) and the N-terminal proBNP fragment, levels of intact proBNP are also increased in heart failure. Moreover, present BNP immunoassays also measure proBNP, as the anti-BNP antibody cross-reacts with proBNP. It is important to know the exact levels of proBNP in heart failure, because elevation of the low-activity proBNP may be associated with the development of heart failure.
We therefore established a two-step immunochemiluminescent assay for total BNP (BNP+proBNP) and proBNP using monoclonal antibodies and glycosylated proBNP as a standard. The assay enables measurement of plasma total BNP and proBNP within only 7 h, without prior extraction of the plasma. The detection limit was 0.4 pmol/L for a 50-µl plasma sample. Within-run CVs ranged from 5.2%–8.0% in proBNP assay and from 7.0%–8.4% in total BNP assay, and between-run CVs ranged from 5.3–7.4% in proBNP assay and from 2.9%–9.5% in total BNP assay, respectively. The dilution curves for plasma samples showed good linearity (correlation coefficients = 0.998–1.00), and analytical recovery was 90–101%. The mean total BNP and proBNP in plasma from 116 healthy subjects were 1.4±1.2 pM and 1.0±0.7 pM, respectively, and were 80±129 pM and 42±70 pM in 32 heart failure patients. Plasma proBNP levels significantly correlate with age in normal subjects.
Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma.
Pro-brain natriuretic peptide (proBNP) is synthesized in the left ventricle. In response to transmural pressure, it is secreted into the circulation and consequently cleaved to yield the active hormone BNP and its N-terminal fragment (NT-proBNP). Determination of NT-proBNP is used as an aid in the diagnosis of left ventricular dysfunction.
We analyzed NT-proBNP-levels before left-heart catheterization in 115 patients. At the end of the study, we compared the NT-proBNP values to the invasively measured hemodynamic indices (left ventricular ejection fraction, maximum change in pressure over time [dP/dtmax] and left ventricular end-diastolic pressure) and the clinically observed New York Heart Association (NYHA) classifications.
A significant (P=0.008) increase of the NT-proBNP values was observed in cases of low ejection fraction (less than 41%). Furthermore, a significant (P=0.03) increase of the NT-proBNP values was measured in cases of heavily reduced dP/dtmax (less than 1500 mmHg/s). The increase of NT-proBNP values in cases of high end-diastolic pressures was distinct but not significant. In the clinical observation (NYHA classification), a significant increase of NT-proBNP levels corresponded to increasing severity of heart failure. However, a large standard deviation was seen in all groups.
Concerning low ejection fractions, a high end-diastolic pressure and strong reduced dP/dtmax in all cases an increase of pro-BNP-values was seen. However, the partly reported strong correlation of the BNP value to the left ventricular ejection fraction, dP/dtmax and left ventricular end-diastolic pressure results was not found in the cases of middle and moderate heart failure, in contrast to the clinical observation. Regarding the large standard deviation, it may be possible to discriminate an unfavourable course of heart failure in an early stage.
Heart failure; Left heart catheterization; Left ventricular hemodynamics; N-terminal pro-brain natriuretic peptide
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
Diastolic dysfunction as demonstrated by tissue Doppler imaging (TDI), particularly E/e' (peak early diastolic transmitral/peak early diastolic mitral annular velocity) is common in critical illness. In septic shock, the prognostic value of TDI is undefined. This study sought to evaluate and compare the prognostic significance of TDI and cardiac biomarkers (B-type natriuretic peptide (BNP); N-terminal proBNP (NTproBNP); troponin T (TnT)) in septic shock. The contribution of fluid management and diastolic dysfunction to elevation of BNP was also evaluated.
Twenty-one consecutive adult patients from a multidisciplinary intensive care unit underwent transthoracic echocardiography and blood collection within 72 hours of developing septic shock.
Mean ± SD APACHE III score was 80.1 ± 23.8. Hospital mortality was 29%. E/e' was significantly higher in hospital non-survivors (15.32 ± 2.74, survivors 9.05 ± 2.75; P = 0.0002). Area under ROC curves were E/e' 0.94, TnT 0.86, BNP 0.78 and NTproBNP 0.67. An E/e' threshold of 14.5 offered 100% sensitivity and 83% specificity. Adjustment for APACHE III, cardiac disease, fluid balance and grade of diastolic function, demonstrated E/e' as an independent predictor of hospital mortality (P = 0.019). Multiple linear regression incorporating APACHE III, gender, cardiac disease, fluid balance, noradrenaline dose, C reactive protein, ejection fraction and diastolic dysfunction yielded APACHE III (P = 0.033), fluid balance (P = 0.001) and diastolic dysfunction (P = 0.009) as independent predictors of BNP concentration.
E/e' is an independent predictor of hospital survival in septic shock. It offers better discrimination between survivors and non-survivors than cardiac biomarkers. Fluid balance and diastolic dysfunction were independent predictors of BNP concentration in septic shock.
The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.
We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.
MR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P < 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P < 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate).
MR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease.
The aim of this study was to assess the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting late cardiotoxicity in patients treated with not-high-dose chemotherapy (NHDC), and to compare the predictive value of NT-proBNP and cardiac troponin I (cTnI).
In 71 patients undergoing NHDC with anthracyclines, NT-proBNP and cTnI levels were measured before and 24 h after each NHDC cycle. Left ventricular (LV) function was assessed by echocardiography at baseline, every two NHDC cycles, at the end of chemotherapy, and at 3-, 6- and 12-month follow-up.
During NHDC, only NT-proBNP showed abnormal values. According to NT-proBNP behaviour, patients were divided into two groups: group A (n=50) with normal (n=23) or transiently elevated NT-proBNP levels (n=27), and group B (n=21) with persistently elevated NT-proBNP levels. At follow-up, LV impairment was significantly worse in group B than in group A. %Δ (baseline–peak) NT-proBNP was predictive of LV impairment at 3-, 6- and 12-month follow-up, with a cutoff of 36%.
Serial measurements of NT-proBNP may be a useful tool for the early detection of patients treated with NHDC at high risk of developing cardiotoxicity.
anthracyclines; brain natriuretic peptide; cardiac biomarkers; cardiotoxicity; N-terminal pro-brain natriuretic peptide