N-terminal pro-B-type Natriuretic Peptide Measurements Research Articles

Heart failure with preserved ejection fraction, atrial fibrillation, and increased NT‑proBNP levels : An emergent clinical dilemma.

The co-presence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) may cause some diagnostic difficulties, because AF itself is associated with elevated levels of N‑terminal pro-B-type natriuretic peptide (NT-proBNP). In the present study we aimed to investigate NT-proBNP levels of patients with HFpEF and AF. This was aretrospective cohort study. Outpatient data were reviewed through the hospital data management system. Consecutive patients with the diagnosis of HFpEF and AF, who had at least one NT-proBNP measurement, were included in the study. The study population comprised 235patients. Median NT-proBNP levels were 1242 pg/ml in the stable phase and 2321.5 pg/ml during decompensation. NT-proBNP was correlated positively with age, CHA2DS2 and CHA2DS2VASc scores, left atrial diameter (LAD), tricuspid annulus diameter, and systolic pulmonary artery pressure but negatively correlated with left ventricular ejection fraction (LVEF) and hemoglobin level. The change in NT-proBNP was positively correlated with heart rate and LAD. Patients with HFpEF and AF have higher levels of NT-proBNP, which may exceed the upper limits defined in guidelines. This study underlines the importance of measuring NT-proBNP levels in the stable phase and proposes arule-in level for the decompensated phase.

Long-term biological variability and the generation of a new reference interval for plasma N-terminal pro-B-type natriuretic peptide in Labrador retrievers.

First, to investigate the biological variability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in healthy Labrador retrievers and compare this with current laboratory recommendations for dilated cardiomyopathy screening. Second, to calculate a breed-specific reference interval and validate it in a retrospective cohort. Plasma NT-proBNP was measured in 51 clinically healthy Labrador retrievers at 0, 2, 4, 6 and 8 weeks. Coefficient of variation for individual dogs over time, the coefficient of variation for the group at each time point and the index of individuality were calculated. A reference interval was derived and tested on a clinical dataset available from four UK cardiology referral centres. Median NT-proBNP was 865 pmol/L (315 to 2064 pmol/L). Mean individual coefficient of variation was 19% (95% CI: 16 to 21%) and group coefficient of variation was 43% (95% CI: 41 to 46%), with index of individuality at 0.44. The breed-specific reference interval was 275 to 2100 pmol/L. In the validation group, 93% of NT-proBNP measurements from healthy dogs were within the reference interval. NT-proBNP measurements exceeded the reference interval in 82% of dogs with dilated cardiomyopathy. The upper bound of the reference interval (2100 pmol/L) had a positive predictive value of 90% and a negative predictive value of 87% for identification of dilated cardiomyopathy in this population. Breed-specific reference intervals might improve the diagnostic accuracy of NT-proBNP measurement. Applying the currently recommended general cut-off value to Labradors is likely to result in frequent false positives and diagnosis would be improved by application of the new breed-specific reference interval calculated here.

Serial Measurements of N-Terminal Pro-B-Type Natriuretic Peptide Serum Level for Monitoring Pulmonary Arterial Hypertension in Children

To assess the association between serially measured N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels and disease severity in children with pulmonary arterial hypertension (PAH), and to assess its predictive value for death or (heart-)lung transplantation. This was a longitudinal cohort study of the Dutch National Network for Pediatric Pulmonary Hypertension conducted between 2003 and 2017. Data on NT-proBNP and disease severity markers (World Health Organization Functional Class [WHO-FC], 6-minute walking distance [6MWD], and tricuspid annular plane systolic excursion [TAPSE]) were collected every 3 to 6months from 82 children with PAH. The outcome measure was death or (heart-)lung transplantation. Also, NT-proBNP levels over time were compared between survivors and nonsurvivors. The median patient age was 8.8years (IQR, 4.6-13.5years), and 61% were female. The median duration of follow-up was 4.8years (IQR, 1.9-10.0years). At all times during the course of disease, higher NT-proBNP levels were associated with higher WHO-FC (β=0.526; 95% CI, 0.451-0.600), lower 6MWD z-score (β=-0.587; 95% CI, -0.828 to -0.346), lower TAPSE z-score (β=-0.783; 95% CI, -1.016 to -0.549), and elevated risk of death or (heart-)lung transplantation (hazard ratio 16.61; 95% CI, 7.81-35.33). Compared with survivors, nonsurvivors had NT-proBNP levels that were higher at first measurement and increased exponentially over time (P=.005). Changes in NT-proBNP serum level over time were predictive of outcome. Throughout the disease course of pediatric PAH, serial measurements of NT-proBNP are associated with disease severity and transplant-free survival. Monitoring NT-proBNP levels over time provides important prognostic information that can support clinical decision making in combination with other established prognostic markers.

A Point-of-Care Measurement of NT-proBNP for Heart Failure Patients

Heart Failure (HF) diagnosis, subsequent admissions, and possible readmissions present challenges for health systems worldwide. An increasing number of patients within an ageing population are surviving cardiac conditions which can leave them with residual heart function impairment. Follow-up visits of either confirmed HF sufferers or HF high-risk patients could be reduced through the implementation of Point-of-Care (PoC) measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP), an inactive signal portion of the active hormone BNP that is released in response to cardiac wall stretch. Serial measurements of NT-proBNP concentration may serve to indicate progress/deterioration of HF sufferers which in turn indicates the quality of the interventions designed to treat HF. We present an integrated PoC solution that involves the user-friendly, low volume sampling of blood directly into a single-use sampling key with an integral NT-proBNP biomarker detection strip operating on a lateral flow immunoassay principle. When inserted into a corresponding portable electronic reader it forms an integrated detection and measurement platform that wirelessly communicates measurements (Wi-Fi) for cloud-based reporting, trending and data analysis. The system provides a practical, inexpensive support tool for HF management by informing those involved in clinical decision-making with necessary biomarker data. The PoC NT-proBNP measurement compares well against alternative technologies based on image analysis.

NT-proBNP Concentration and Early Cardiac Dysfunction in Patients Receiving Dialysis: A Prospective Cohort Study

Introduction: The significance of N-terminal pro-B type natriuretic peptide (NT-proBNP) to detect heart failure in patients with end-stage kidney diseases on dialysis is controversial. Objective: To assess whether serial measurements of NT-proBNP can predict worsening cardiac function in dialysis patients. Methods: In this prospective, longitudinal, observational cohort study, the relationship between changes in monthly plasma NT-proBNP concentrations and changes in echocardiographic indices (left ventricular global longitudinal strain [GLS] and ejection fraction [LVEF]) were analyzed in dialysis patients without symptoms of heart failure over 24 months using multilevel mixed effects models. Results: The study included 40 dialysis patients who were followed for a median period of 24 months. Logarithmically transformed baseline plasma NT-proBNP levels were correlated positively with GLS (r = 0.48, p = 0.002) and negatively with LVEF (r = –0.44, p = 0.005). Time-averaged and maximum NT-proBNP values during the echocardiogram intervals were significantly correlated with GLS and LVEF over time. Every 1-unit increase in average NT-proBNP level during the echocardiogram interval was associated with a 0.99 (95% confidence interval, 0.41–1.56) higher GLS (%) and 2.90 (1.22–4.57) lower LVEF (%). Every 1-unit increase in maximum NT-proBNP level was associated with a 0.90 (0.35–1.45) higher GLS (%) and 2.67 (1.03–4.30) lower LVEF (%). This increase in GLS indicates a reduction in systolic performance. Conclusions: Our cohort study demonstrated that serial plasma NT-proBNP concentrations may be useful for early identification of individuals with worsening cardiac function over time.

P1644Personalized screening intervals for measurement of n-terminal pro-b-type natriuretic peptide improve efficiency of prognostication in patients with chronic heart failure

Abstract Background Predefined screening intervals and target levels do not account for variations in temporal patterns of biomarkers between individuals, which may hamper their potential use for therapy guidance. Conversely, a personalized screening approach with screening intervals and target levels based on the evolution of biomarkers in individual patients may further improve risk assessment and therapy guidance. Purpose We hypothesize that personalized screening intervals for N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements in patients with chronic heart failure (CHF) maximize information gain on the individual patient's disease progression, while minimizing the number of necessary measurements. We aim to compare such personalized scheduling of NT-proBNP measurements to a predefined fixed scheduling approach. Methods In 263 CHF patients from the Bio-SHiFT study, NT-proBNP was measured trimonthly according to a prespecified, fixed schedule [median: 9 (IQR: 5–10) measurements per patient].The primary composite endpoint (PE) comprised cardiac death, cardiac transplantation, left ventricular assist device implantation or heart failure hospitalization, and occurred in 70 patients (26.6%). Using joint models for time-to-event and longitudinal data, we modelled the association between repeated NT-proBNP measurements and the PE. Using the fitted joint model, for each patient at each follow-up visit, we determined the optimal time point of the next NT-proBNP measurement based on the patient's individual risk profile and the maximum information gain on the patient's prognosis as assessed by the Kullback-Leibler divergence. Personalized scheduling was compared to fixed (trimonthly) scheduling by means of a realistic simulation study, based on a replica of the study population included in the Bio-SHiFT study. In this simulation study, we stopped monitoring NT-proBNP to potentially enable appropriate timely intervention if the cumulative risk of PE exceeded an arbitrary risk threshold of 7.5% within 3-months. We compared personalized scheduling with fixed scheduling in terms of capability of identification of high-risk intervals (whether timely intervention was enabled before occurrence of PE), number of measurements needed, and costs. Results Compared to fixed scheduling, personalized scheduling saved on average 2 measurements [personalized; median: 7 (IQR: 7–8) vs. fixed; 9 (IQR: 8–10) measurements], while the start of the time-window identified for therapeutic intervention to avoid the occurrence of PE was similar in both approaches [personalized; median: 6.6 (IQR: 4.5–11.3) vs. fixed; 6.3 (IQR: 4.2–10.3) months before occurrence of PE]. Costs saved were €165 per patient per year. Figure 1 Conclusion Personalized scheduling of NT-proBNP measurements in CHF patients shows similar prognostic performance as fixed scheduling, but requires fewer NT-proBNP measurements. This may improve efficiency of natriuretic guided therapy, if the latter were to be installed. Acknowledgement/Funding Funding for this study was provided by the Jaap Schouten Foundation and Erasmus MC Efficiency Research grant

N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker of Bronchopulmonary Dysplasia or Death in Preterm Infants: A Retrospective Cohort Analysis.

Objectives: To investigate the association between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level on the first day of life and a composite outcome of bronchopulmonary dysplasia (BPD) or death in a cohort of infants born before 32 weeks of gestation.Methods: We retrospectively identified infants born before 32 weeks of gestation who had serum NT-proBNP levels measured when they were admitted to the Neonatal Intensive Care Unit shortly after birth. The outcome of BPD or death was assessed at 36 weeks of postmenstrual age. The association of serum NT-proBNP levels with BPD or death was evaluated. Receiver operator characteristic (ROC) curve analysis was used to evaluate the predictive performance of serum NT-proBNP levels.Results: A 100 and 47 preterm infants had serum NT-proBNP levels measured on the first day of life. Serum NT-proBNP level was significantly higher in preterm infants who developed moderate/severe BPD or died [3,855 (2,567–6,369) vs. 1,259 (950–2,035) in control infants, P < 0.001]. On binary regression analysis, a high natural logarithm of serum NT-proBNP levels was associated with increased risk of moderate/severe BPD or death adjusted for gestational age, birth weight, birth weight z-score, and Apgar scores at 1 and 5 min (odds ratio [OR] = 5.195, 95% confidence interval [CI] 2.667–10.117, P < 0.001). ROC analysis identified a NT-proBNP level of 2002.5 pg/mL to have 87.5% sensitivity and 74.7% specificity for predicting moderate/severe BPD or death. The area under the curve (AUC) was 0.853 (95% CI 0.792–0.914).Conclusion: Serum NT-proBNP level measured on the first day of life is a promising biomarker for predicting the development of moderate/severe BPD or death in preterm infants. Our findings warrant a larger prospective study to incorporate measurement of NT-proBNP in prognosticating outcomes in very preterm infants.

NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and the Risk of Stroke.

Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.

Association of N-terminal pro B-type natriuretic peptide (NT-proBNP) change with the risk of atrial fibrillation in the ARIC cohort

Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts incidence of atrial fibrillation (AF), but the association of longitudinal changes in NT-proBNP concentrations with incident AF has not been explored. We studied 9705 individuals without prevalent AF in 1996-1998 and with available NT-proBNP measurements obtained in samples collected during two visits in 1990-1992 (visit 2) and 1996-1998 (visit 4) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed through the end of 2013. AF was ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox regression was used to evaluate the association of absolute change in log-transformed NT-proBNP [ln(NT-proBNP)] with incident AF. We also assessed the impact of adding ln(NT-proBNP) change as a predictor of AF by difference in the C-statistic and net reclassification improvement (NRI). Over a median follow up of 16 years, there were 1503 incident cases of AF. The means (SD) ln(NT-proBNP) at visit 2 and visit 4 were 3.83 (1.01) and 4.35 (0.94), respectively. There was a 0.52 (0.79) increase in ln(NT-proBNP) over the 6-year period. Greater increases in ln(NT-proBNP) were associated with higher risk of AF [hazard ratio, 2.82 (95% confidence interval 2.34, 3.39), comparing top to bottom quintiles, and 1.74 (1.61, 1.87) per 1-unit increase in ln(NT-proBNP)]. Adding ln(NT-proBNP) change to a model with multiple predictors including baseline NT-proBNP had relatively limited impact in the C-statistic (increase from 0.748, 95%CI 0.736-0.761, to 0.762, 95%CI 0.750, 0.774). Adding ln(NT-proBNP) change to initial predictive models resulted in a categorical NRI of 0.062 (95% CI 0.033, 0.092) and a continuous NRI of 0.092 (95%CI, 0.017, 0.182). Positive NT-proBNP change is associated with an increased incidence rate of AF. Adding NT-proBNP change into the prediction model modestly improved incident AF prediction. Future studies should assess the value of monitoring NT-proBNP concentration among individuals at high risk of developing AF.

Is elevation of N-terminal pro-B-type natriuretic peptide at discharge associated with 2-year composite endpoint of all-cause mortality and heart failure hospitalisation after transcatheter aortic valve implantation? Insights from a multicentre prospective OCEAN-TAVI registry in Japan

ObjectivesThe aim of this study was to investigate the 2-year prognostic impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at discharge following transcatheter aortic valve implantation (TAVI).DesignMulticentre prospective observational study.SettingsSeven...

HeartLogic Multisensor Algorithm Identifies Patients During Periods of Significantly Increased Risk of Heart Failure Events: Results From the MultiSENSE Study.

Care of heart failure (HF) patients results in a high burden on healthcare resources, and estimating prognosis is becoming increasingly important to triage resources wisely. Natriuretic peptides are recommended prognosticators in chronic HF. Our objective was to evaluate whether a multisensor HF index and alert algorithm (HeartLogic) replaces or augments current HF risk stratification. MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) enrolled 900 patients with cardiac resynchronization therapy defibrillators enabled for collection of heart sounds, respiration, thoracic impedance, heart rate, and activity data. The HeartLogic algorithm automatically calculated a daily HF index and identified periods IN or OUT of an active alert state relative to a configurable threshold. Patients experienced 192 independently adjudicated HF events (average rate, 0.20/patient-year [pt-yr]) during 1 year of follow-up. HF event rates while IN alert was 10-fold higher than OUT of alert (0.80 versus 0.08 events/pt-yr). Combined with NT-proBNP (N-terminal pro-B-type natriuretic peptide) at enrollment (relative to 1000 pg/mL threshold, event rate was 0.42 [HIGH] versus 0.07 [LOW] events/pt-yr), substratification found the lowest risk group (LOW NT-proBNP and OUT of alert) experienced 0.02 events/pt-yr, whereas the highest risk group (HIGH NT-proBNP and IN alert) was associated with a 50-fold increased risk of an HF event (1.00 events/pt-yr) relative to the lowest risk group. Dynamic assessment using implantable device sensors within HeartLogic by itself or in conjunction with NT-proBNP measurements can identify time-intervals when patients are at significantly increased risk of worsening HF and potentially better triage resources to this vulnerable patient population. https://www.clinicaltrials.gov. Unique identifier: NCT01128166.

N-Terminal Pro-B-Type Natriuretic Peptide Is Not a Significant Predictor of Stroke Incidence After 5 Years - The Ohasama Study.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used for risk stratification in heart failure or acute coronary syndrome, but the beyond 5-year predictive value of NT-proBNP for stroke remains an unsettled issue in Asian patients. The aim of the present study was to clarify this point.Methods and Results:We followed 1,198 participants (33.4% men; mean age, 60.5±11.1 years old) in the Japanese general population for a median of 13.0 years. A first stroke occurred in 93 participants. Referencing previous reports, we stratified participants according to NT-proBNP 30.0, 55.0, and 125.0 pg/mL. Using the NT-proBNP <30.0 pg/mL group as a reference, adjusted HR for stroke (95% CI) in the NT-proBNP 30.0-54.9-pg/mL, 55.0-124.9-pg/mL, and ≥125.0-pg/mL groups were 1.92 (0.94-3.94), 1.77 (0.85-3.66), and 1.99 (0.86-4.61), respectively. With the maximum follow-up period set at 5 years, the hazard ratio of the NT-proBNP≥125.0-pg/mL group compared with the <30.0-pg/mL group increased significantly (HR, 4.51; 95% CI: 1.03-19.85). On extension of the maximum follow-up period, however, the association between NT-proBNP and stroke risk weakened. NT-proBNP was significantly associated with an elevated stroke risk. Given, however, that the predictive power decreased with the number of years after NT-proBNP measurement, NT-proBNP should be re-evaluated periodically in Asian patients.

Abstract MP05: N Terminal Pro B Type Natriuretic Peptide as a Stroke Risk Factor in the European Population: Results From the Biomarcare Consortium

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a risk factor for atrial fibrillation and a marker of cardiac function used in detection of heart failure. Few studies evaluated the role of NT-proBNP as risk factor for stroke. Hypothesis: Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke outcomes and to determine the predictive value beyond a panel of established risk factors for stroke. Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project we analysed data of 43,815 participants (48.3% men; mean age 52 yr) free of cardiovascular disease from 6 prospective population-based cohorts across Europe with a maximum follow-up of 22 years. All NT-proBNP measurements were performed on frozen samples in the central BiomarCaRE laboratory. The endpoints considered were validated fatal and non-fatal stroke. Results: We observed 565 stroke events (78 fatal) in men and 290 (54) in women. Growing quartiles of NT-proBNP were associated with increasing risk of stroke (Table; multivariable cox regression analysis adjusted for the base model: age, centre, smoking, BMI, diabetes, hypertension medication, systolic and diastolic blood pressure, total and HDL cholesterol), both in men (p for trend &lt;0.0001) and in women (P&lt;0.0001). Examining C-statistics for prediction of stroke we could observe only very small changes after the addition of NT-proBNP to the base model (delta AUC=0.0053 and 0.0048 in men and women, respectively). Conclusions: In European individuals free of cardiovascular disease, levels of NT-proBNP in the top quartile (&gt;87.7 pg/mL) are associated with a doubled risk of stroke. However, the addition of NT-proBNP to variables of established risk score poorly improves prediction of stroke disease.

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

BackgroundContemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. ObjectivesThis study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. MethodsDyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. ResultsOf 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). ConclusionsIn acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.

The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac surgical patients

BackgroundEuropean System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known. MethodsPreoperative (n=640) and postoperative (n=629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2). ResultsSixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho=0.58; p<0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134–1354) ng/L [NT-proBNP] and 39 (16–191) vs. 13 (8–32) ng/L [hs-TnT]; p<0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [lnNT-proBNP] 1.33 [95% CI 1.08–1.64]), p=0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14–0.64], p=0.003). Pre- and postoperative NT-proBNP concentrations were closely correlated (rho=0.80, p<0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurements ConclusionNT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients.

Left atrial expansion index predicts left ventricular filling pressure in ischemic cardiomyopathy

The aim of the study was to assess the power of left atrial expansion index (LAEI) to predict left ventricular filling pressures and its relation with N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with ischemic cardiomyopathies. This prospective study analyzed 66 patients (mean age 62 ± 11 years, range 37–89, 86.4% male) with ischemic cardiomyopathy (mean Left ventricular ejection fraction 46.4 ± 12.8%). All patients underwent transthoracic echocardiography and NT-proBNP measurement within 24 hours. The LAEI was calculated as (Vol max − Vol min) × 100%/Vol min, where Vol max was defined as maximal LA volume and Vol min was defined as minimal volume. Simple regression analysis demonstrated a significant linear correlation between LAEI and Log NT-proBNP( r = 0.723, P < 0.0001). Significant but weaker correlations were found between Log NT-proBNP and E/E’ ( r = 0.504, P < 0.0001), indexed LA maximum volume (LAVI max) ( r = 0.308, P = 0.012), mitral deceleration time (TDE) ( r = 0.365, P = 0.003), E/A ( r = 0.362, P = 0.003). Significant correlations were also found between LAEI and E/E’ ( r = −0.543, P < 0.0001), LAVI max ( r = 0.360, P = 0.003), E/A ( r = 0.403, P = 0.001). The receiver-operating characteristic curve showed that LAEI had good diagnostic power for E/E’ > 15 at cutoff value of 66.8% with a sensitivity of 74.5% and a specificity of 83.3% while the area under the curve was of 0.875. Multivariate analysis techniques with Log-NT-proBNP as dependent variable and age, E/A, TDE, E/E’, LAVI max and LAEI as predictors, showed that the relation to LAEI was the strongest ( β = −0.725). We suggest that evaluation of LAEI may be useful to predict LV filling pressures in ischemic cardiomyopathies. The power of this index exceeds that of other well-established echocardiographic parameters such as E/E’ and LVAI max.

N-terminal pro–B-type natriuretic peptide for monitoring after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment option for chronic thromboembolic pulmonary hypertension (CTEPH). The non-invasive monitoring of CTEPH patients is a clinical challenge. In this study we examined changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients undergoing BPA for inoperable CTEPH and related them to peri-procedural success. In this study we analyzed a total of 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between March 2014 and March 2017. Serum samples for NT-proBNP measurement were collected before every BPA and at 6-MFU. The 51 patients underwent 265 interventions involving angioplasty of a total of 410 vessels. The 6-month survival rate was 96.1%. The baseline (BL) mean pulmonary artery pressure (PAP) was 39.5 ± 12.1 mm Hg, pulmonary vascular resistance (PVR) was 515.8 ± 219.2 dynes/s/cm5 and the median NT-proBNP level was 820 (153 to 1,871.5) ng/liter. At BL, World Health Organization functional class (FC) was ≥III in 96.1% of the patients, whereas, at 6-MFU, 11.8% were in WHO FC ≥III. At 6-MFU, mean PAP (32.6 ± 12.6 mm Hg; p < 0.001), PVR (396.9 ± 182.6 dynes/s/cm5; p < 0.001) and NT-proBNP (159.3 [84.4 to 464.3] ng/liter; p < 0.001) levels were reduced. The decrease in NT-proBNP levels correlated with the decrease in mean PAP (rrs = 0.43, p = 0.002) and PVR (rrs = 0.50, p = 0.001). A reduction in the NT-proBNP level of 46% indicated a decrease in mean PAP of ≥25% (area under the curve [AUC] = 0.71) and a reduction of 61% indicated a decrease in PVR of ≥35% (AUC 0.77). Our results demonstrate that NT-proBNP levels decrease after BPA, providing valuable evidence of procedural success. NT-proBNP measurement allows identification of patients who are BPA non-responders and may thus be a valuable adjunct in therapy monitoring.

Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats

BackgroundCats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion.Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions.ResultsSix cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion.ConclusionsPOC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

Association of Elevated NT-proBNP With Myocardial Fibrosis in the Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundSerum N-terminal pro–B-type natriuretic peptide (NT-proBNP) is considered a marker that is expressed in response to myocardial strain and possibly fibrosis. However, the relationship to myocardial fibrosis in a community-based population is unknown. ObjectivesThe authors evaluated the relationship between cardiac magnetic resonance (CMR) measures of fibrosis and NT-proBNP levels in the MESA (Multi-Ethnic Study of Atherosclerosis) study. MethodsA total of 1,334 participants (52% white, 23% black, 11% Chinese, 14% Hispanic, and 52% men with a mean age of 67.6 years) at 6 sites had both serum NT-proBNP measurements and CMR with T1 mapping of indices of fibrosis at 1.5 T. Univariate and multivariable regression analyses adjusting for demographics, cardiovascular risk factors, and left ventricular (LV) mass were performed to examine the association of log NT-proBNP with CMR T1 mapping indices. ResultsIn the fully adjusted model, each 1-SD increment (0.44 pg/ml) of log NT-proBNP was associated with a 0.62% increment in extracellular volume fraction (p < 0.001), 0.011 increment in partition coefficient (p < 0.001), and 4.7-ms increment in native T1 (p = 0.001). Results remained unchanged after excluding individuals with clinical cardiovascular disease or late gadolinium enhancement (n = 167), and after replacing LV mass by LV end-diastolic volume in the regression models. ConclusionsElevated NT-proBNP is related to subclinical fibrosis in a community-based setting. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.