Use Of N-terminal pro-B-type Natriuretic Peptide Research Articles

NT-proBNP for heart failure diagnosis in Primary Care: Costs or savings? A budget impact study

Introduction and objectivesChronic heart failure (CHF) is a growing public health concern and diagnosis can be challenging, particularly in primary care. This study aims to estimate the budgetary impact of introducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) for CHF diagnosis in a primary care setting from the perspective of the Portuguese health system. MethodsA budget impact analysis was conducted over one-year from the patients’ first presentation. The standard of care (SoC) was compared to NT-proBNP at the point-of-care (PoC) or laboratory (Lab). A decision tree model was used to estimate the downstream costs associated with each of the three pathways. ResultsAn estimated 81 012 patients were expected to present to primary care with new onset CHF symptoms. The use of NT-proBNP as a primary diagnostic tool is estimated to generate annualized savings of EUR 935 657 and EUR 2 982 443 in the Lab and PoC setting, respectively. Estimated cost savings were due to the need for fewer medical visits, hospitalizations and echocardiograms (ECHO). The Lab and PoC settings led to similar reductions in hospitalizations (14.4%) and ECHO (27%), but the reduction in medical visits was higher in the PoC setting (38% compared to 2.5%), resulting in higher savings compared to Lab. ConclusionsUsing NT-proBNP for CHF diagnosis in primary care could result in considerable costs savings for the public health system in Portugal. This evidence might support health policy makers to reconsider the resource management and define a new strategy to mitigate the impact of CHF.

Current use of NT-proBNP in elderly patients and the impact of the selected threshold value: lessons from a big data analysis

Abstract Background Natriuretic peptides (NPs) are widely used in the diagnosis and risk stratification of heart failure (HF).NPs may have a reduced discriminative ability in the subgroup of elderly patients. Methods We examined all biological tests performed from February 2010 to August 2015 in two districts in the French Brittany. We report the “real-world” use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an elderly population and examine the measured concentration and potential impact of the cut-off value's selection. Results From a total of 3,606,432 tests ordered in 557,650 adult patients, 56,653 included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased by 10-y age categories up to 80–90 y, and 39,828 (70.3%) of all measurements have been done in patients ≥75y. NT-proBNP concentrations increased with advanced age (Pearson's correlation coefficient: 0.2; p<10–5), with concentrations of 3,564±6,440 ng/L in patients ≥75y. NT-proBNP was inversely correlated with creatinine clearance (p<10–5). Respective proportions of NT-proBNP below the threshold value were 22.6% in patients aged 70 to 80y and less than 10% in those over 80 y when considering a single threshold value of 125 ng/L, and 31% and 33% in the same groups when considering a dual age-adjusted threshold value of 450 ng/L in patients >75y (p<0.001 for all comparisons). Conclusion Among a very large cohort, we observed that NT-proBNP is increasingly measured in elderly patients. NT-proBNP concentrations increase with age, and the selection of the threshold value markedly impacts the proportion of “low” versus “high” results. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Roche Diagnostics Proportion (in %) of low NT-proBNP

Does N-Terminal Pro-B-Type Natriuretic Peptide Improve the Risk Stratification of Emergency Department Patients With Syncope?

Studies have reported that natriuretic peptides provide prognostic information for emergency department (ED) syncope. To evaluate whether adding N-terminal pro-B-type natriuretic peptide (NT-proBNP) to the Canadian Syncope Risk Score (CSRS) improves prediction of 30-day serious adverse events (SAEs). Prospective cohort study. 6 EDs in 2 Canadian provinces. 1452 adult ED patients with syncope. Serum NT-proBNP was measured locally at 1 site and batch processed at a central laboratory from other sites. The concentrations were not available to treating physicians or for adjudication of outcomes. An adjudicated composite outcome of 30-day SAEs, including death and cardiac (arrhythmic and nonarrhythmic) and noncardiac events. Of 1452 patients enrolled, 152 (10.5% [95% CI, 9.0% to 12.1%]) had 30-day SAEs, 57 (3.9%) of which were identified after the index ED disposition. Serum NT-proBNP concentrations were significantly higher among patients with SAEs than those without them (median, 626.5 ng/L vs. 81 ng/L; P < 0.001). Adding NT-proBNP values to the CSRS did not significantly improve prognostication (c-statistic, 0.89 and 0.90; P= 0.12 for difference), regardless of SAE subgroup or whether the SAE was identified after the index ED visit. The net reclassification index shows that NT-proBNP would have correctly reclassified 3% of patients with SAEs at the expense of incorrectly reclassifying 2% of patients without SAEs. Our study was powered to detect a 3% difference in the area under the curve. The heterogeneity of outcomes and robust baseline discrimination by the CSRS will make improvements challenging. Although serum NT-proBNP concentrations were generally much higher among ED patients with syncope who had a 30-day SAE, this blood test added little new information to the CSRS. Routine use of NT-proBNP for ED syncope prognostication is not recommended. Physicians' Services Incorporated Foundation, Canadian Institutes of Health Research, and The Ottawa Hospital Academic Medical Organization.

Systemic Inflammation and Cardio-Renal Organ Damage Biomarkers in Middle Age Are Associated With Physical Capability Up to 9 Years Later.

Physical capability, a key component of healthy aging, is associated with cardiovascular and other risk factors across life. We investigated whether midlife biomarkers of heart and kidney damage capturing the cumulative impact of long-term adverse exposures were associated with the level and decline in physical capability over 9 years of follow-up, taking account of systemic inflammatory biomarkers and conventional cardiovascular risk factors. We used data on 1736 men and women from the oldest British birth cohort study with walking speed, chair rise speed, balance time, and grip strength assessed at ages 60 to 64 and 69 years. We tested associations between logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-B-type natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years with performance at age 69 years, adjusting for sex, height, and body mass index; then for performance at age 60 to 64 years. These biomarkers were mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin), diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime socioeconomic position. Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely associated with all outcomes, adjusted for sex, height, and body mass index. For example, a 1-SD increase in logged NT-proBNP was associated with weaker grip (-0.63 kg, 95% CI, -0.99 to -0.28); the equivalent association for cystatin C was -0.60 kg (95% CI, -0.94 to -0.25) and for IL-6 was -0.76 kg (95% CI, -1.11 to -0.41). Most associations remained, albeit attenuated, after adjustment for previous performance and mutual adjustment of the biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly associated with the outcomes than many of the conventional risk factors after mutual adjustment. Higher levels of NT-proBNP may identify those in midlife at risk of accelerated physical decline. Before considering the use of NT-proBNP for risk stratification, further research should untangle whether these associations exist because the biomarker is an integrated measure of cumulative exposures to relevant stressors across life, or whether it is marking additional risk pathways. Randomized trials to reduce the rate of decline in physical capability or delay incident disability could benefit from including middle-aged adults and adding NT-proBNP and IL-6 as intermediate outcomes.

Associations With and Prognostic and Discriminatory Role of N-Terminal Pro–B-Type Natriuretic Peptide in Heart Failure With Preserved Versus Mid-range Versus Reduced Ejection Fraction

BackgroundThe aim of this study was to characterize N-terminal pro–B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) versus preserved (HFpEF) and reduced (HFrEF) ejection fraction. Methods and ResultsIn 9847 outpatients with HFpEF (n = 1811; 18%), HFmrEF (n = 2122; 22%) and HFrEF (n = 5914; 60%) enrolled in the Swedish Heart Failure Registry, median NT-proBNP levels were 1428, 1540, and 2288 pg/mL, respectively. Many determinants of NT-proBNP differed by ejection fraction, with atrial fibrillation (AF) more important in HFmrEF and HFpEF, diabetes and hypertension in HFmrEF, and age and body mass index in HFrEF and HFmrEF, whereas renal function, New York Heart Association functional class, heart rate, and anemia were similar. Hazard ratios for death and death/HF hospitalization for NT-proBNP above the median ranged from 1.48 to 2.00 and were greatest for HFmrEF and HFpEF. Areas under the receiver operating characteristic curve for death and death/HF hospitalization were greater in HFmrEF than in HFpEF and HFrEF and were reduced by AF in HFpEF and HFmrEF but not in HFrEF. ConclusionsIn HFpEF and especially HFmrEF, NT-proBNP was more prognostic and discriminatory, but also more affected by confounders such as AF. These data support the use of NT-proBNP for eligibility, enrichment, and surrogate end points in HFpEF and HFmrEF trials, and suggest that cutoff levels for eligibility should be carefully tailored to comorbidity.

Electrochemical impedimetric detection of stroke biomarker NT-proBNP using disposable screen-printed gold electrodes

Abstract Stroke is the second top leading cause of death globally. It is caused by an abrupt interruption of blood flow to the brain. In that course, brain natriuretic peptide (BNP) and its derivative N-terminal pro b-type natriuretic peptide (NT-proBNP), neurohormones produced mainly by the heart ventricles in response to excessive stretching of cardiomyocytes (heart muscle cells), are proven to be good biomarkers for heart failure diagnosis. Moreover, there is growing clinical interest of the use of NT-proBNP for stroke diagnosis and prognosis because it is significantly associated with cardioembolic stroke and secondary stroke reoccurrence, with sensitivity &gt;90% and specificity &gt;80%. However, in diagnostic settings, there is still a need to address the encountered analytical problems, particularly assay specificity and set up. In this study, a novel approach for NT-proBNP detection is demonstrated using an electrochemical immunoassay method. A label-free impedimetry immunosensor for stroke biomarker was developed using modified disposable screen-printed gold electrodes (SPGE) hosting specific anti-NT-proBNP capture antibody. The performance of our immunosensor was studied in the presence of NT-proBNP in both buffered and mock (porcine) plasma samples. A linear relation between the relative total resistance (ΔRtot) responses and the NT-proBNP concentrations in buffer was observed in a range from 0.1 to 5 ng mL-1 with a correlation coefficient (R2) of 0.94656. Overall, the biosensor has demonstrated the capability to quantitate NT-proBNP and differentiate such concentrations in a low concentration range, especially among 0, 0.1, 0.5, 1, and 3 ng mL-1 in plasma samples within 25 min. This range is valuable not only for classifying cardioembolic stroke (higher or equal to 0.5 ng mL-1), but also predicting the risk of secondary stroke reoccurrence (higher than 0.255 ng mL-1). Our biosensor has the potential to be used as an easy-to-use point-of-care test that is both accurate and affordable.

NT-proBNP Best Predictor of Cardiovascular Events and Cardiovascular Mortality in Secondary Prevention in Very Old Age: The Leiden 85-Plus Study

BackgroundIn the aging population cardiovascular disease (CVD) is highly prevalent. Identification of very old persons at high risk of recurrent CVD is difficult, since traditional risk markers loose predictive value with age. MethodsIn a population-based sample of 282 85-year old participants with established CVD from the Leiden 85-plus Study, we studied predictive values of traditional cardiovascular risk markers, a history of major CVD (myocardial infarction, stroke or arterial surgery), and new cardiovascular biomarkers (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP), homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding 5-year risk of recurrent cardiovascular events and mortality (composite endpoint).ResultsDuring complete 5-year follow-up 157 (56%) participants died. 109 (39%) had a cardiovascular event or died from cardiovascular causes. Individually related to the composite endpoint were: a history of major CVD (HR 1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI 1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of all five new markers only addition of NT-proBNP improved the C-statistic (0.67 (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and for homocysteine 24.7% (p=0.04). ConclusionsAmong very old subjects with established CVD, NT-proBNP was the strongest risk marker for cardiovascular events and cardiovascular mortality. When estimating risk in secondary prevention in very old age, use of NT-proBNP should be considered.

N-terminal Pro B-type Natriuretic Peptide in the Early Evaluation of Suspected Acute Myocardial Infarction

Background Myocardial ischemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release. As ischemia precedes necrosis in acute myocardial infarction, we hypothesized that NT-proBNP might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction. Methods In a prospective multicenter study, NT-proBNP was measured at presentation in 658 consecutive patients with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed long term regarding mortality. Results Acute myocardial infarction was the adjudicated final diagnosis in 117 patients (18%). NT-proBNP levels at presentation were significantly higher in acute myocardial infarction as compared with patients with other final diagnoses (median 886 pg/mL vs 135 pg/mL, P <.001). The diagnostic accuracy of NT-proBNP for acute myocardial infarction as quantified by the area under the receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval [CI], 0.75-0.83). When added to cardiac troponin T, NT-proBNP significantly increased the AUC from 0.89 (95% CI, 0.84-0.93) to 0.91 (95% CI, 0.88-0.94; P = .033). Cumulative 24-month mortality rates were 0% in the first, 1.3% in the second, 8.3% in the third, and 23.3% in the fourth quartile of NT-proBNP ( P <.001). NT-proBNP (AUC 0.85, 95% CI, 0.81-0.89) predicted all-cause mortality independently of and more accurately than both cardiac troponin T (AUC 0.66, 95% CI, 0.58-0.74; P <.001) and the Thrombolysis in Myocardial Infarction risk score (AUC 0.79, 95% CI, 0.74-0.84; P <.001). Net reclassification improvement (Thrombolysis in Myocardial Infarction vs additionally NT-proBNP) was 0.188 ( P <.009), and integrated discrimination improvement was 0.100 ( P <.001). Conclusions Use of NT-proBNP improves the early diagnosis and risk stratification of patients with suspected acute myocardial infarction.

Ruling out heart failure in primary-care: The cost-benefit of pre-screening using NT-proBNP and QRS width

Background Half of the patients presenting to primary-care with signs and symptoms of heart failure (HF) are found not to have serious heart disease after echocardiographic assessment. This places an unnecessary burden on hospital services. We sought to assess the cost-benefit of screening for left ventricular systolic dysfunction (LVSD) and major structural heart disease (SHD) using N-terminal pro-B-type natriuretic peptide (NT-proBNP) and QRS-width from an electrocardiogram in patients presenting with suspected HF to primary-care physicians (PCP). Methods Patients were recruited from a community-based service pilot. Blood samples for NT-proBNP measurement were obtained in primary-care. All patients were referred irrespective of the NT-proBNP result, with echocardiograms reviewed by a cardiologist blinded to the NT-proBNP result. Results NT-proBNP< 180 pg/ml (21 pmol/l) ‘ruled-out’ major-LVSD avoiding 38% of echoes and 23% of cost compared with direct referral for echocardiography. NT-proBNP< 93 pg/ml (11 pmol/l) ‘ruled-out’ major-SHD, avoiding 20% of echoes and 8% of cost. A QRS< 84 ms ‘ruled-out’ major-LVSD, avoiding 28% of echoes and 17% of cost. A QRS< 82 ms ‘ruled-out’ major-SHD avoiding 20% of echoes and 9% of cost. Intermediate values of NT-proBNP were often associated with equivocal echocardiography and in some scenarios NT-proBNP testing might avoid 61% of echocardiograms and 46% of cost. Conclusion Use of NT-proBNP by PCPs to detect major-LVSD and major-SHD in patients with suspected HF could reduce referrals for specialist HF-assessment, provide cost-avoidance compared to direct referral and improve the efficiency of care. QRS-width is less effective as a diagnostic test and adds little cost-benefit when combined with NT-proBNP.