Title: a Systematic Review of BNP and NT-Probnp in the Management of Heart Failure: Overview

Title: A Systematic Review of BNP and NT-proBNP in the Management of Heart Failure: Overview and Methods

Journal: Heart Failure

Authors: Mark Oremus, Robert McKelvie, Andrew Don-Wauchope, Pasqualina L. Santaguida, Usman Ali, Cynthia Balion, Stephen Hill, Ronald Booth, Judy A. Brown, Amy Bustamam, Nazmul Sohel, and Parminder Raina

Corresponding Author and Contact Requests:

Parminder Raina, PhD

Department of Clinical Epidemiology and Biostatistics

McMaster University

1280 Main Street West

MIP Suite 309A

Hamilton, Ontario

Canada L8S 4K1

Email:

Tel: 905-525-9140 x22197

Table AF2-1: Inclusion and Exclusion Criteria /
/ Population / Intervention/Prognos-tic Factors / Comparators / Outcomes / Timing of Follow-up / Setting /
KQ1 / Presentation with HF symptoms.
Exclusion: Participants ≤18 years of age, presenting with already diagnosed acute HF or known exacerbation of stable chronic HF, comorbid conditions impacting BNP results (e.g., heart transplant, obesity, hypertrophic cardiomyopathy, valvular lesions). / Measures of BNP/NT-proBNP at admission or discharge or measure of change in BNP/NT-proBNP between admission and discharge. / Any method of diagnosing HF that does not use BNP or NT-proBNP. / Test performance characteristics (i.e., sensitivity, specificity, positive and negative LRs, diagnostic odds ratio [DOR], area under the ROC curve),
cutpoints, effect of various determinants (e.g., age, sex, and comorbidities) on the test performance, adverse effects related to test administration. / Any length of follow-up acceptable. / Emergency or urgent care departments only.
KQ2 / Presentation with HF symptoms.
Exclusion: Participants ≤18 years of age, presenting with already diagnosed acute HF or known exacerbation of stable chronic HF, comorbid conditions impacting BNP results (e.g., heart transplant, obesity, hypertrophic cardiomyopathy, valvular lesions). / Measures of BNP/NT-proBNP at admission or discharge or measure of change in BNP/NT-proBNP between admission and discharge. / Any method of diagnosing HF that does not use BNP or NT-proBNP. / Test performance characteristics (i.e., sensitivity, specificity, positive and negative LRs, diagnostic odds ratio [DOR], area under the ROC curve),
cutpoints, effect of various determinants (e.g., age, sex, and comorbidities) on the test performance, adverse effects related to test administration. / Any length of follow-up acceptable. / Primary care settings only.
KQ3 / Any HF (with or without any comorbidity). Exclusion: Risk of CAD or with CAD, risk of HF without documented HF (e.g., diabetes and renal failure). / BNP or NT-proBNP measured at admission, discharge, or change between admission and discharge.
Exclusions: Univariate analysis only. / NYHA functional classification of stages of HF, ejection fraction, degree of hypona-tremia, decreasing peak exercise oxygen uptake, decreasing hematocrit, widened QRS interval on 12-lead electrocardiogram, chronic hypotension, resting tachycardia, renal insufficiency, intolerance to conventional therapy, refractory volume overload, or risk prediction scores (e.g., Seattle HF Model). / Mortality including all-cause and HF, morbidity including hospitalization (including HF, all-cause, planned, and unplanned), change in NYHA class, quality of life. / Any length of follow-up acceptable. / Acute care hospitals, outpatient clinics/ambulatory care settings, hospital settings, or family practice settings.
KQ4 / Any HF (with or without any comorbidity). Exclusion: Risk of CAD or with CAD, risk of HF without documented HF (e.g., diabetes and renal failure). / BNP or NT-proBNP measured at admission, discharge, or change between admission and discharge; any other prognostic factors compared with BNP or NT-proBNP using the appropriate statistical metrics.*
Exclusion: Studies that used simple extensions of AUC without accounting for time or events, studies that used only the log rank test. / NYHA functional classification of stages of HF, ejection fraction, degree of hypona-tremia, decreasing peak exercise oxygen uptake, decreasing hematocrit, widened QRS interval on 12-lead electrocardiogram, chronic hypotension, resting tachycardia, renal insufficiency, intolerance to conventional therapy, refractory volume overload, or risk prediction scores (e.g., Seattle HF Model). / Mortality including all-cause and HF, morbidity including hospitalization (including HF, all-cause, planned, and unplanned), change in NYHA class, quality of life. / Any length of follow-up acceptable. / Acute care hospitals, outpatient clinics/ambulatory care settings, hospital settings, or family practice settings.
KQ5 / No disease (a nonselected or general population).
Exclusion: Use of any specific disease to include or exclude participants from study. / BNP or NT-proBNP measured at admission, discharge, or change between admission and discharge. / Any predictive scoring system (e.g., Framingham). / Mortality including all-cause and HF, morbidity including hospitalization (including HF, all-cause, planned, and unplanned), change in NYHA class, quality of life. / Any length of follow-up acceptable. / Primary care settings only.
KQ6 / Receiving treatment for chronic HF.
Exclusion: Persons admitted with known HF or acute HF. / Any medical therapy based on BNP or NT-proBNP concentration. / Medical therapy based on usual care for HF patients (no BNP or NT-proBNP concentration). / Mortality including all-cause and HF, morbidity including hospitalization (including HF, all-cause, planned, and unplanned), change in NYHA class, quality of life. / Any length of follow-up acceptable. / Any setting acceptable.
KQ7 / Adults with or without HF. / Multiple measurements of BNP or NT-proBNP in study participants. / N/A / Calculation of biological variation. / Any length of follow-up acceptable. / Any setting acceptable.

*Includes likelihood-based measures, such as LR and LR chi-square (global chi-square and incremental chi-square), indices of calibration, such as the Hosmer-Lemeshow statistic (goodness-of-fit test), discrimination statistics, such as c-index or c-statistics, and measures of risk reclassification, such as Net Reclassification Improvement and Integrated Discrimination Improvement (IDI).

Notes: For all KQs, study participants had to be at least 18 years of age and an FDA-approved assay designed specifically for BNP or NT-proBNP had to be used to measure the peptide. No exclusions unless otherwise stated in table cells.

Abbreviations: AUC = area under the curve; BNP = brain natriuretic peptide; CAD = coronary artery disease; DOR = diagnostic odds ratio; FDA = Food and Drug Administration; HF = heart failure; KQ = key question; LR = likelihood ratio; N/A = not applicable; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; NYHA = New York Heart Association.