Multicenter reference limits of hs-cTnI and NT-proBNP in a Chinese cohort.

Aim To identify predictors of increased N-terminal pro-brain natriuretic peptide (NT-proBNP) in a population of outpatients at a high risk for chronic heart failure (CHF) using methods based on the clinical decision limit (CDL), reference intervals (RI), and age- and sex-adjusted NT-proBNP ratio.Material and methods Timely diagnosis and initiation of treatment at the early stages of CHF improve the prognosis of patients. Accordingly, a program for supporting patients at a high-risk of CHF by measuring NT-proBNP was implemented in all federal districts (FDs) of the Russian Federation. The analysis included 11,740 patients at high risk of developing CHF, who had a single NT-proBNP measurement in an outpatient setting. The inclusion criteria were age >18 years, symptoms and signs of CHF and/or abnormalities on electrocardiogram and/or the presence of diseases (arterial hypertension and/or any form of ischemic heart disease). The analysis included determining the proportion of patients with NT-proBNP test results above the CDL (NT-proBNP ≥125 pg/ml) and above the RI (97.5th percentile). For additional assessment, the age- and gender-adjusted NT-proBNP ratio was used. The risk of elevated NT-proBNP was assessed based on CDL, RI, and the NT-proBNP ratio.Results The median age of patients was 66 [58.0; 73.0] years, 55.8% were >65 years, and 59.3% were women. In 43.5% of patients, the NT-proBNP concentration was less than 125 pg/ml. The risk of achieving CDL was 50% higher among men, associated with the patient's age, and increased by 73% in the 45-54 age group, 2.52 times in the 55-64 age group, and 6.62 times in the >65 years age group compared to the 18-44 age group. Living in a city with a population of less than one million people increased the risk of achieving CDL by 17% compared to living in a city with a population of over a million. NT-proBNP values above the RI were achieved by 22% of patients, with the risk being 69% higher among men and 24% higher among patients living in cities with a population of less than one million. Evaluation of the NT-proBNP test results using the RI criterion showed that 44.3% of patients with normal RI values had NT-proBNP values above the CDL (≥125 pg/ml). The NT-proBNP ratio was the lowest in the Ural Federal District and the highest in the Far Eastern Federal District. The risk of an increased NT-proBNP ratio ≥1 was higher among men by 67% (p<0.001), for residents of small towns by 21% (p<0.001), and for residents of the Far Eastern Federal District compared to any other region (p<0.001).Conclusion Independent risk factors for elevated NT-proBNP when assessed by the RI and NT-proBNP ratio included male gender, residence in cities with a population of less than one million, and residence in the Far Eastern Federal District. Assessing the NT-proBNP test solely based on the CDL, without taking into account physiological changes related to gender and age, carries a risk of overdiagnosis of CHF.

Article, see p 1671 Heart failure (HF) hospitalization presents a substantial burden to patients, hospitals, and payors. Hospitals face competing incentives from government payors because prolonged lengths of stay risk unreimbursed costs beyond the fixed reimbursement, whereas premature discharge increases the risk of 30-day readmission, for which hospitals can be penalized on a much broader scale. Clinicians have struggled to define the objective criteria regarding readiness for discharge from a HF hospitalization, which should address not only relief of congestion, but also evaluation of etiology, enhancement of guideline-directed therapies, review of disease trajectory, and consolidation of outpatient management. Once gaps in the transition process have been closed, the major cause of readmission is recurrent congestion. Regardless of how congestion is documented,1–3 patients who go home “wet” are likely to return “wetter”. Quality improvement and cost containment efforts are converging to design care pathways that begin early during hospitalization to ensure adequate decongestion by discharge. Employment of brain natriuretic peptide (BNP) levels as targets for therapy arose naturally from the robust predictive value of BNP levels and changes in levels, further supported by their close relationship with elevated cardiac filling pressures4,5 and recognized as a hemodynamic determinant of outcomes. Utility of a biomarker as a target for therapy requires not only clinical relevance, but also timely responsiveness to the therapy titration, and unique information beyond usual clinical assessments. Multiple trials have used natriuretic peptides as targets for adjustment of chronic outpatient therapy with neurohormonal antagonists6–10 (Figure). When uptitration was aggressive in response to persistently high levels of natriuretic peptides, outcomes were better than without such uptitration.9 However, when the design encouraged vigorous …

We report a blinded, prospective study of the diagnostic utility of N-terminal pro-brain natriuretic peptide (NTproBNP) measurements for predicting clinically significant patent ductus arteriosus (PDA) and assessing closure. Plasma NTproBNP was measured during the first week in 100 preterm babies (mean gestation 28.8 +/- 2.9 weeks; mean birth weight 1224 +/- 512 g). Echocardiography was performed between days 5 and 7 by operators, blinded to NTproBNP concentration. NTproBNP peaked on days 2 and 3, declined by day 7. Twenty babies, later treated for PDA, had significantly higher NTproBNP levels throughout. Areas under receiver operating characteristic (ROC) curves were 0.896, 0.897 and 0.931 on days 2, 3 and 7, respectively (p < 0.0001). A concentration > 2850 pmol/L had diagnostic sensitivity of 90% and specificity of 89% (95% CI: 68, 99; likelihood ratio 8.10). Ductal closure was associated with a fall in mean NTproBNP from 3003 to 839 pmol/L (p < 0.001). N-terminal pro B-type brain natriuretic peptide (NTproBNP) concentrations peaked and then declined in the first week but remained higher in preterm babies whose PDA required treatment. NTproBNP on day 3 predicted whether a neonatal physician blinded to results would treat a PDA. Fall in plasma NTproBNP indicated closure.

N-Terminal Pro-B-Type Natriuretic Peptide as an Indicator of Disease Severity in a Heterogeneous Group of Patients With Chronic Precapillary Pulmonary Hypertension

Abstract. Objectives. This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in com-munity-dwelling elderly people would provide additional prognostic information to that from traditional risk factors. Background. Accurate cardiovascular risk stratification is challenging in elderly people. Methods. NT-proBNP was measured at baseline and 2 to 3 years later in 2975 community-dwelling older adults free of heart failure in the longitudinal Cardiovascular Health Study (CHS). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders. Results. NT-proBNP levels in the highest quintile (>267.7 pg/mL) were independently associated with greater risks of HF (hazard ratio [HR], 3.05; 95% confidence interval [CI], 2.46–3.78) and cardiovascular death (HR, 3.02; 95% CI, 2.36–3.86) compared with the lowest quintile (<47.5 pg/mL). The inflection point for elevated risk occurred at NT-proBNP 190 pg/mL. Among participants with initially low NT-proBNP (<190 pg/mL), those with a >25% increase on follow-up to >190 pg/mL (21%) were at greater adjusted risk for HF (HR, 2.13; 95% CI, 1.68–2.71) and cardiovascular death (HR, 1.91; 95% CI, 1.43–2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those with a >25% increase (40%) were at higher risk for HF (HR, 2.06; 95% CI, 1.56–2.72) and cardiovascular death (HR, 1.88; 95% CI, 1.37–2.57), whereas those with a >25% decrease to ≤190 pg/mL (15%) were at lower risk for HF (HR, 0.58; 95% CI, 0.36–0.93) and cardiovascular death (HR, 0.57; 95% CI, 0.32–1.01) compared with those with unchanged high values. Conclusions. NT-proBNP levels independently predict HF and cardiovascular death in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk. deFilippi CR, Christenson RH, Gottdiener JS, et al. Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic testing. J Am Coll Cardiol. 2010; 55: 441-450.

BackgroundChihuahua represents an increasingly widespread breed predisposed to cardiac disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be a useful point-of-care biomarker for dogs suspected of having heart disease, but breed differences have been reported. The urinary aldosterone-to-creatinine ratio (UAldo: C) appears to be a good indicator of renin-angiotensin-aldosterone system activity in dogs, but Chihuahuas showed significantly higher UAldo: C than other breeds. The objective of this study was to assess preliminary breed-specific reference intervals for NT-proBNP and UAldo: C in healthy Chihuahuas and evaluate sex differences in these parameters.ResultsForty-three healthy Chihuahuas dogs were enrolled. The median NT-proBNP was 347 (125–515) pmol/L, and the median UAldo: C was 2.59 (1.57–4.61) µg/g. The NT-proBNP reference interval was 125 (90% CI 125–125) – 2121.4 (90% CI 941.6–2248) pmol/L. 91% of the Chihuahuas were below the nonbreed-specific cut-off (900 pmol/L). The UAldo: C reference interval was 0.6 (90% CI 0.5–0.9) – 16.8 (90% CI 10.9–27.4) µg/g. No significant sex differences in NT-proBNP or UAldo: C were found.ConclusionsThe median value, interindividual coefficient of variation and reference interval of NT-proBNP were in line with those reported for other small breeds. In contrast to previous studies, no sex differences in NT-proBNP were detected. As previously suggested, Chihuahuas seem to be characterized by higher values of UAldo: C than other breeds.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker used in the clinical management of heart failure. We sought to create updated reference intervals for NT-proBNP for healthy US children, adolescents, and adults. We identified a population of healthy individuals using the 1999 to 2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We measured serum NT-proBNP in 12 346 adults and 15 752 children and adolescents with the Elecsys NT-proBNP assay on the Roche e601 autoanalyzer. We compared 4 methods for reference interval calculation, and presented the final reference intervals using the robust method partitioned by age and sex categories. NT-proBNP values were available for 1949 healthy adults and 5250 healthy children and adolescents. NT-proBNP concentrations in males and females varied according to age, being higher in early childhood, relatively lower in late adolescence, and highest through middle age and older age. Females tended to have higher NT-proBNP concentrations compared to men from late adolescence until middle age. The upper reference limit, or 97.5th percentile, for 50 to 59 year-old men was 225 ng/L (90% CI: 158 to 236), and for 50 to 59 year-old women, 292 ng/L (90% CI: 242 to 348). Among healthy individuals, NT-proBNP concentrations varied greatly according age and sex. The reference intervals presented here should inform future clinical decision limits and suggest that age- and sex-specific intervals may be necessary to more precisely characterize risk.

N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Is Associated with Both Left Ventricular Diastolic Dysfunction and Myeloma-Related Renal Insufficiency and Robustly Predicts Mortality in Patients with Symptomatic Multiple Myeloma

N-terminal pro B-type natriuretic peptide (NT-proBNP) is a natriuretic peptide that is strongly associated with congestive heart failure (CHF). The utility of NT-proBNP for prediction of cardiovascular events and renal endpoints, compared with clinical risk factors, has not been evaluated in detail. We hypothesise that NT-proBNP can improve risk stratification and prediction of cardiorenal events in type 2 diabetes, beyond that provided by clinical risk factors. NT-proBNP was measured in 1993 samples from the Hong Kong Diabetes Biobank, a multicentre prospective diabetes cohort and biobank. A cut-off of ≥125 pg/ml was used to define elevated NT-proBNP. Associations between elevated NT-proBNP and incident cardiovascular and renal endpoints were examined using Cox regression, adjusted for sex, age and duration of diabetes, as well as other covariates. Prognostic and incremental predictive values of NT-proBNP in diabetes cardiorenal complications, compared with those of the Joint Asia Diabetes Evaluation risk equations for CHD, CHF and kidney failure, were evaluated using the concordance index (C index), net reclassification improvement index, integrated discrimination improvement index and relative integrated discrimination improvement index. A total of 24.7% of participants had elevated NT-proBNP. Participants with elevated NT-proBNP at baseline had a more adverse cardiometabolic profile, with 2-4-fold higher frequency of complications at baseline. Adjusting for age at baseline, sex and duration of diabetes, elevated NT-proBNP was associated with incident atrial fibrillation (HR 4.64 [95% CI 2.44, 8.85]), CHD (HR 4.21 [2.46, 7.21]), CVD (HR 3.32 [2.20, 5.01]) and CHF (HR 4.18 [2.18, 8.03]; all p<0.001). All these associations remained significant after further adjustment for additional covariates. Elevated NT-proBNP had good discriminative ability for various cardiorenal endpoints, with C index of 0.83 (95% CI 0.76, 0.90) for CHD, 0.88 (0.81, 0.94) for atrial fibrillation, 0.89 (0.83, 0.95) for CHF, 0.81 (0.77, 0.84) for 40% drop in eGFR and 0.88 (0.84, 0.92) for kidney failure. Models incorporating NT-proBNP had improved prediction compared with established clinical risk models. Sensitivity analyses including alternative cut-off of NT-proBNP, as well as use of other risk engines of CHD, yielded similar results. NT-proBNP demonstrated a promising ability to serve as a prognostic marker for a variety of cardiorenal complications in type 2 diabetes. Considering NT-proBNP in clinical assessments could potentially help identify high-risk individuals who may benefit from more intensive therapies.

Circulating levels of natriuretic peptides (NP) are inversely related to body mass index (BMI), and obese patients with heart failure (HF) have lower brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations than nonobese patients.1,2 These observations have raised concerns about the prognostic value of NP in patients with HF with an elevated BMI. Prior observational studies suggested that NP may retain their capacity to predict mortality across all BMI categories in HF with individuals with reduced ejection fraction.3,4 Nevertheless, these studies included a relatively small number of events and did not evaluate additional cardiovascular end points. Because it remains uncertain whether BMI may influence the prognostic utility of NP in patients with HF, we examined the influence of BMI on the predictive value of NT-proBNP and BNP in patients with reduced ejection fraction from the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure; URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255). The design and primary results of the PARADIGM-HF trial have been previously described.5 The patients randomized in the trial (n=8399) were required to have a plasma BNP ≥150 pg/mL or an NT-proBNP ≥600 pg/mL or, if they were hospitalized for HF within the previous …

IntroductionNeurohormonal activation in patients with chronic heart failure (CHF) causes plasma volume expansion which, if untreated, leads to overt venous congestion. Plasma volume status (PVS) can be estimated using formulae...

Since the late 1980s, elevated atrial natriuretic peptide (ANP) was considered the cause of brisk diuresis in adult patients with paroxysmal supraventricular tachycardia (PSVT). Pro-brain natriuretic peptide (pro-BNP) and related molecules, e.g., N-terminal pro b-type natriuretic peptide (NT-pro-BNP) are known biomarkers of heart failure in adult patients from many causes with probable relevance in children. Perhaps, pro-BNP or related molecules such as NT-pro-BNP are useful in the management of PSVT in infants, thus hastening treatment in children who may otherwise significantly decompensate. Case series of one infant and two neonates presenting with cardiogenic shock and evidence of heart failure are presented. Cardiac monitoring or electrocardiogram (ECG) confirmed the presence of PSVT. Adenosine was administered resulting in successful chemical cardioversion with each case. Significantly elevated NT-pro-BNP levels correlated with heart failure prior to cardioversion. In each case, patients were discharged home with lower NT-pro-BNP levels and maintenance with a β-blocker. Due to documented relationships between elevated pro-BNP level and heart failure in adults, the authors measured the related biomarker NT-pro-BNP in each case, as the relationship could be similar in pediatric PSVT. Based on our experience with children in acute heart failure from other causes, NT-pro-BNP can increase to potentially extreme levels in infants. It appears to correlate with clinical signs of insufficient cardiac output, such as tachycardia, respiratory distress, and moribund appearance. Indeed, in the case series, extremely high NT-pro-BNP values were obtained when the patients appeared moribund from decompensated PSVT. The question arising from these observations is: At what level of elevated NT-pro-BNP, would patients be identified for cardioversion prior to appearance of other signs and symptoms? For each patient within the case series, NT-pro-BNP levels of approximately 20,000 pg/mL were indicative of decompensated heart failure, which was subsequently confirmed by examination of the patient. Further investigation is needed to determine the clinical significance of NT-pro-BNP and related peptides in pediatric patients with PSVT and intermittent PSVT. However, the possibility exists that an increase in NT-pro-BNP and related peptides could be a biomarker for cardiac decompensation after prolonged or intermittent PSVT, thereby shortening the time of diagnosis and intervention, and hence, potentially preventing morbidity, mortality, and extended hospitalization. Additional evidence-based research would help provide biomarker information during PSVT allowing practitioners to more objectively analyze risks.

AimsThis multicentre study investigated the association of periprocedural changes in the levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with clinical outcomes after transcatheter edge‐to‐edge mitral valve repair (TMVR).Methods and resultsPatients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT‐proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT‐proBNP following TMVR were assessed as the percent change in NT‐proBNP between baseline and the 2 month follow‐up, and the significant reduction in NT‐proBNP was defined as a decrease of >30% in the follow‐up NT‐proBNP compared with the pre‐procedural NT‐proBNP level. Primary outcome was defined as a composite outcome consisting of all‐cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut‐off value of pre‐procedural NT‐proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut‐off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT‐proBNP (>30%) following the procedure. Patients with the NT‐proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT‐proBNP (31.4% vs. 40.2%; log‐rank P = 0.03). The significant reduction in NT‐proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45–0.97; P = 0.04], independently of pre‐procedural NT‐proBNP levels and other clinical parameters. The percent change in NT‐proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94–0.98; P < 0.001). A stratified analysis revealed that the prognostic impact of the significant reduction in NT‐proBNP was consistent among clinical subgroups, including aetiology of mitral regurgitation (P for interaction = 0.99). Higher pre‐procedural NT‐proBNP level (>2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03–2.17; P = 0.03); however, patients with a higher pre‐procedural NT‐proBNP who achieved the significant reduction in NT‐proBNP had a similar risk of the composite outcome to those with a lower pre‐procedural NT‐proBNP.ConclusionsChanges in sequential NT‐proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT‐proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post‐procedural management after TMVR.

Objective: To explore the predictive value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on admission on left ventricular ejection fraction (LVEF) and the in-hospital major adverse cardiac and cerebrovascular events (MACCE) in hospitalized patients with unstable angina (UA). Methods: Data of 2 972 consecutive hospitalized patients with UA in Beijing Friendship Hospital from January 2013 to September 2017 were retrospective analyzed. Patients were divided into 4 groups according to the level of NT-proBNP on admission: 733 cases with NT-proBNP lower than 61 ng/L, 749 cases with NT-proBNP between 61 and 133 ng/L, 747 cases with NT-proBNP between 133 and 326 ng/L, and 743 cases with NT-proBNP higher than 326 ng/L. LVEF and in-hospital MACCE were compared among 4 groups and the predictive value of NT-proBNP on admission on LVEF and in-hospital MACCE was determined by multiple logistical regression analysis. Results: LVEF value became lower with increasing on admission NT-proBNP value ((68.4±4.8)%, (68.2±5.2)%, (67.2±6.7)% and (62.6±10.4)%, F=77.98, P<0.01), while in-hospital MACCE was higher with increasing on admission NT-proBNP value (3.4% (25/733), 3.5% (26/749), 5.5% (41/747) and 7.3% (54/743), χ(2)=16.23, P<0.01) in NT-proBNP lower than 61 ng/L, NT-proBNP between 61 and 133 ng/L, NT-proBNP between 133 and 326 ng/L, and NT-proBNP higher than 326 ng/L group. Multiple logistic regression analysis showed that on admission NT-proBNP was an independent predictor for LVEF<50% (Exp(β)=5.875, 95%CI 3.382-10.207, P<0.001), but not predictor for in-hospital MACCE (Exp(β)=0.783, 95%CI 0.400-1.996, P=0.783). Conclusion: The on admission NT-proBNP level is an independent predictor of left ventricular systolic dysfunction (LVEF<50%), but not an independent predictor of total in-hospital MACCE in hospitalized patients with UA.

Cardiac myosin-binding protein C as a candidate biomarker in heart failure: rational but not revolutionary.