A Novel N-Terminal Pro-B-Type Natriuretic Peptide Assay in the Early Diagnosis of Acute Heart Failure

Figures

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  Figure 1. Direct Comparison of Both NT-proBNP Assays (A) Boxplots show the distribution of NT-proBNP levels (pg/mL) for the NT-proBNP-Access and NT-proBNP-Elecsys assays in the overall cohort. Bars indicate medians; box bottoms and tops, 25th and 75th percentiles; whiskers, upper and lower adjacent values; dots, outliers. (B) Scatterplot with NT-proBNP-Elecsys on x-axis and NT-proBNP-Access on y-axis. Red dots represent patients with AHF, green, without AHF, black dashed line x = y. (C) Quantile regression with restricted cubic splines using 5 knots. Red dots indicate patients with AHF, green dots, patients without; gray diagonal represents x = y. (D) The x-axis represents the mean of NT-proBNP measurements (Elecsys and Access) for a pertaining patient. The y-axis represents the difference between the NT-proBNP concentrations (Elecsys-Access). The blue line is the mean of the difference between both assays. The red dashed lines are the upper and lower limits of agreement (mean of the difference +/− SD of the difference∗1.96). Patients are stratified according to the final adjudicated diagnosis. AHF = acute heart failure; NT-proBNP = N-terminal pro–B-type natriuretic peptide.

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  Figure 2. Diagnostic Accuracies of NT-proBNP Assays in Diagnosing Acute Heart Failure The area under the receiver operating characteristics curve is 0.914 (95% CI: 0.898-0.930) for the NT-proBNP-Access and 0.922 (95% CI: 0.908-0.937) for the NT-proBNP-Elecsys (DeLong test P = 0.006). Abbreviations as in Figure 1.

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  Figure 3. Performance of Both Assays Across Predefined Subgroups Clinical subgroups: (A) sex, (B) age (<50, 50-75, >75 years), (C) body mass index (<30, ≥30 kg/m2), (D) renal function (eGFR >60, 30-60, <30 mL/min/1.73 m2), and (E) atrial fibrillation on admission. P value for comparison between the 2 depicted groups calculated using DeLong test, eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. AUC = Area under the receiver operating characteristics curve; eGFR = estimated glomerular filtration rate; other abbreviations as in Figure 1.

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  Figure 4. Triage Pathway to Diagnose Acute Heart Failure (A) Performance of NT-proBNP-Access and NT-proBNP-Elecsys using the universal NT-proBNP rule out cutoff concentration (<300 pg/mL) and age-dependent rule in cutoff concentrations (>450 pg/mL if < 50 years, >900 pg/mL if 50-75 years, and >1,800 pg/mL if >75 years). (B) Sensitivity (TPR), specificity (TNR) and negative predictive value (NPV) for NT-proBNP-Access and NT-proBNP-Elecsys levels using the universal NT-proBNP rule out cutoff concentration (<300 pg/mL, dashed vertical line). AHF = acute heart failure; NPV = negative predictive value; PPV = positive predictive value; TNR = true negative rate; TPR = true positive rate; other abbreviations as in Figure 1.

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  Central Illustration. Evaluation of the Performance of a Novel NT-proBNP Assay at Guideline-Recommended Decision Values Comparison of the diagnostic accuracy and the performance of NT-proBNP-Access and NT-proBNP-Elecsys using the universal NT-proBNP rule-out cut-off concentration (<300 pg/mL) and age-dependent rule-in cut-off concentrations (>450 pg/mL if <50 years, >900 pg/mL if 50-75 years, and >1,800 pg/mL if >75 years). AHF = acute heart failure; AUC = area under the receiver operating characteristic curve; ED = emergency department; NPV = negative predictive value; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PPV = positive predictive value.

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  Figure 5. Diagnostic Concordance Between NT-proBNP-Access and NT-proBNP-Elecsys (A) A disagreement was considered major (lilac) in those cases where the triage decision for 1 assay was rule out (red) whereas for the other one it was rule in (green). Minor disagreements (nude) were defined as instances where 1 assay indicated rule out whereas the other indicated the gray zone (yellow), or when 1 assay indicated the gray zone whereas the other indicated rule-in. These values represent differences in triage categorization (rule-in, rule-out, or gray zone) between assays and do not correspond to false or true positives. Data are represented as a number (percent). (B) Alluvial plot visualizing the diagnostic concordance for acute heart failure between patient classifications into rule-in (red), observe (yellow), and rule-out (green) using either the NT-proBNP-Elecsys assay (left) or the NT-proBNP-Access assay (right). Numbers in triage feels show the absolute number of patients categorized by each assay. Abbreviations as in Figure 1.