The  Diagnostic Utility of Brain Natriuretic Peptide  in Heart Failure Patients Presenting with Acute Dyspnea:  A Systematic Review and Meta-analysis

Mohammad Amin Karimi; Zahra Kazemi Ferezghi; Reza Khademi; Seyed Amirhossein Mazhari; Fatemeh Chichagi; Asma Rasouli; Reyhaneh Alikhani; Anis Sani; Shima Akhavan Rezayat; Nima Shakouri; Seyed Iraj Azimi; Faezeh Jadidian; Golnaz Nikeghbali; Mahfam Edrisian; Alaleh Alizadeh; Niloofar Deravi; Mohadeseh Poudineh; Mahsa Asadi Anar

Authors

Mohammad Amin Karimi School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Zahra Kazemi Ferezghi Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Reza Khademi Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Seyed Amirhossein Mazhari Student Research Committee, Azerbaijan Medical University, Baku, Azerbaijan.
Fatemeh Chichagi Tehran Heart Center, Tehran university of medical science, Tehran, iran
Asma Rasouli School of Medicine, Zanjan University of medical sciences, Zanjan, Iran
Reyhaneh Alikhani Tehran University of medical science
Anis Sani Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Shima Akhavan Rezayat Student research committee, Faculty of Medicine, Islamic Azad University of Mashhad, Mashhad, Iran.
Nima Shakouri School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Seyed Iraj Azimi Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
Faezeh Jadidian Student Research committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Golnaz Nikeghbali Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mahfam Edrisian Student Research Committee, school of Medicine, Iran University of Medical Sciences(IUMS), Tehran, Iran
Alaleh Alizadeh Student Research Committee, Faculty of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Niloofar Deravi Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mohadeseh Poudineh Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Mahsa Asadi Anar Student Research committee, School of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Keywords:

NTproBNP, heart failure, B-type natriuretic peptide, BNP, Meta-analysis

Abstract

Background: Patients with heart failure are often diagnosed based on clinical signs and serological markers. Finding biomarkers with greater sensitivity and specificity for heart failure patients who also have episodic dyspnea is a challenge for researchers. Thus, we conducted a systematic review and meta-analysis of previous research to determine the diagnostic value of B-type natriuretic peptide as a potential biomarker in heart failure patients experiencing acute dyspnea. Methods: By searching PubMed/Medline, Scopus, and Google Scholar up to March 2023, all cross-sectional and cohort studies were selected according to the PRISMA guidelines and assessed by the Deeks’ funnel plot asymmetry test for bias. Results: A total of thirty-five qualifying studies had their data extracted. In 26 investigations (n=16002), the precision of B-type natriuretic peptide was evaluated. There were significant differences in the reported sensitivity and specificity between trials. One research study yielded the lowest sensitivity of 0.76 (0.68, 0.82), with a prevalence of 46% for heart failure and a BNP level of ≥500 pg/ml. Specificity grew but stayed variable as the threshold rose, whereas sensitivity declined. A diagnostic meta-analysis was carried out on 14 trials (n=6313) to determine the accuracy of N-terminal probrain natriuretic peptide. When the threshold is raised, the pattern in NTproBNP is similar to that of B-type natriuretic peptides, with sensitivity falling and specificity increasing. Following the final analysis, the confidence areas surrounding the pooled sensitivity and specificity for BNP vs NTproBNP showed a distinct overlap. The overlap indicated that there was no statistically significant difference between the tests at the <100 pg/ml and ≤300 pg/ml rule-out levels, respectively (P>0.05). Conclusion: The meta-analysis reveals a substantial degree of congruity in the sensitivity and specificity between the levels of BNP and NTproBNP as biomarkers. Nevertheless, it's worth noting that, in the end, there exists a potential for overlooking heart failure diagnoses. Larger future studies, overcoming past limitations, could likely establish a consensus.

References

Campbell ML. Dyspnea. AACN Adv Crit Care. 2011;22(3):257-64.

Wessman T, Tofik R, Ruge T, Melander O. Associations between biomarkers of multimorbidity burden and mortality risk among patients with acute dyspnea. Intern Emerg Med. 2022;17(2):559-67.

Filippatos G, Angermann CE, Cleland JGF, et al. Global differences in characteristics, precipitants, and initial management of patients presenting with acute heart failure. JAMA Cardiol. 2020;5(4):401-10.

Kjellström B, van der Wal MH. Old and new tools to assess dyspnea in the hospitalized patient. Curr Heart Fail Rep. 2013;10(3):204-11.

Kuo DC, Peacock WF. Diagnosing and managing acute heart failure in the emergency department. Clin Exp Emerg Med. 2015;2(3):141-9.

Su Q, Liu H, Zhang X, et al. Diagnostic values of NT-proBNP in acute dyspnea among elderly patients. Int J Clin Exp Pathol. 2015;8(10):13471-6.

Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes. 1997;46(2):271-86.

Strunk A, Bhalla V, Clopton P, et al. Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the breathing not properly multinational study. The American Journal of Medicine. 2006;119(1):69, e1-, e11.

Koulouri S, Acherman RJ, Wong PC, Chan LS, Lewis AB. Utility of B-type natriuretic peptide in differentiating congestive heart failure from lung disease in pediatric patients with respiratory distress. Pediatric Cardiology. 2004;25(4):341-6.

Strunk A, Bhalla V, Clopton P, et al. Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: Results from the breathing not properly multinational study. American Journal of Medicine. 2006;119(1):69.e1-.e11.

Parab R, Vasudevan A, Brensilver J, Gitler B. Utility of brain natriuretic peptide as a diagnostic tool for congestive heart failure in the elderly. Critical Pathways in Cardiology. 2005;4(3):140-4.

Choi S. Cut-off values for B-type natriuretic peptides in Korean patients visiting emergency departments [2]. Emergency Medicine Journal. 2008;25(4):246.

Belmin J, Donadio C, Jarzebowski W, Genranmayeh K, Valembois L, Lafuente-Lafuente C. The value of B-type natriuretic peptide plasma concentrations in very old people with chronic peripheral oedema. Archives of Cardiovascular Diseases. 2020;113(5):332-40.

Mueller T, Gegenhuber A, Poelz W, Haltmayer M. Diagnostic accuracy of B-type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart. 2005;91(5):606-12.

Lader E. BNP levels had high sensitivity but moderate specificity for detecting congestive heart failure in the emergency department. ACP J Club. 2003;138(1):23.

Maisel A. B-type natriuretic peptide measurements in diagnosing congestive heart failure in the dyspneic emergency department patient. Reviews in Cardiovascular Medicine. 2002;3(SUPPL. 4):S10-S7.

Kozhuharov N, Sabti Z, Wussler D, et al. Prospective validation of N-terminal pro B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. European Journal of Heart Failure. 2019;21(6):813-5.

Nazerian P, Vanni S, Zanobetti M, et al. Diagnostic accuracy of emergency Doppler echocardiography for identification of acute left ventricular heart failure in patients with acute dyspnea: Comparison with Boston criteria and N-terminal prohormone brain natriuretic peptide. Academic Emergency Medicine. 2010;17(1):18-26.

Klemen P, Golub M, Grmec S. Combination of quantitative capnometry, N-terminal pro-brain natriuretic peptide, and clinical assessment in differentiating acute heart failure from pulmonary disease as cause of acute dyspnea in pre-hospital Emergency setting: Study of diagnostic accuracy. Croatian Medical Journal. 2009;50(2):133-42.

Maisel AS, McCord J, Nowak RM, et al. Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction: results from the Breathing Not Properly Multinational Study. Journal of the American College of Cardiology. 2003;41(11):2010-7.

Moon JY, Bae JH, Kim TH, et al. The role of plasma B-type natriuretic peptide measurements in the differential diagnosis of acute dyspnea. Tuberculosis and Respiratory Diseases. 2005;59(6):656-63.

Figal DAP, Sánchez MCC, Velasco JAN, et al. Usefulness of NTproBNP in the emergency management of patients with severe dyspnea and an uncertain heart failure diagnosis. Revista Española de Cardiología (English Edition). 2005;58(10):1155-61.

Sartini S, Frizzi J, Borselli M, et al. Which method is best for an early, accurate diagnosis of acute heart failure? Comparison between lung ultrasound, chest X-ray, and NT pro-BNP performance: a prospective study. Internal and emergency medicine. 2017;12:861-9.

Kevin Rogers R, Stehlik J, Stoddard GJ, et al. Adjusting for clinical covariates improves the ability of B-type natriuretic peptide to distinguish cardiac from non-cardiac dyspnoea: a sub-study of HEARD-IT. Eur J Heart Fail. 2009;11(11):1043-9.

Ray P, Arthaud M, Birolleau S, et al. Comparison of brain natriuretic peptide and probrain natriuretic peptide in the diagnosis of cardiogenic pulmonary edema in patients aged 65 and older. J Am Geriatr Soc. 2005;53(4):643-8.

Bal L, Thierry S, Brocas E, et al. B-type natriuretic peptide (BNP) and N-terminal-proBNP for heart failure diagnosis in shock or acute respiratory distress. Acta Anaesthesiol Scand. 2006;50(3):340-7.

Barcarse E, Kazanegra R, Chen A, Chiu A, Clopton P, Maisel A. Combination of B-type natriuretic peptide levels and non-invasive hemodynamic parameters in diagnosing congestive heart failure in the emergency department. Congest Heart Fail. 2004;10(4):171-6.

Arques S, Roux E, Sbragia P, Pieri B, Gelisse R, Luccioni R, et al. Usefulness of bedside tissue Doppler echocardiography and B-type natriuretic peptide (BNP) in differentiating congestive heart failure from noncardiac causes of acute dyspnea in elderly patients with a normal left ventricular ejection fraction and permanent, nonvalvular atrial fibrillation: insights from a prospective, monocenter study. Echocardiography. 2007;24(5):499-507.

Nazerian P, Vanni S, Zanobetti M, et al. Diagnostic accuracy of emergency Doppler echocardiography for identification of acute left ventricular heart failure in patients with acute dyspnea: comparison with Boston criteria and N-terminal prohormone brain natriuretic peptide. Acad Emerg Med. 2010;17(1):18-26.

Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A. Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. Journal of the American College of Cardiology. 2002;39(2):202-9.

Kaleemullah S, Mansoor A. Diagnostic significance of NT-proBNP estimation in patients with acute dyspnea. 2011.

Lader E. B type natriuretic peptide levels had high sensitivity but moderate specificity for detecting CHF in the emergency department.

Choi S, Park D, Lee S, Hong Y, Kim S, Lee J. Cut-off values of B-type natriuretic peptide for the diagnosis of congestive heart failure in patients with dyspnoea visiting emergency departments: a study on Korean patients visiting emergency departments. Emergency Medicine Journal. 2007;24(5):343-7.

Mueller T, Gegenhuber A, Poelz W, Haltmayer M. Diagnostic accuracy of B-type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart. 2005;91(5):606-12.

Knudsen CW, Westheim A, Omland T. B-type natriuretic peptide and clinical judgement in the diagnosis of heart failure in patients presenting with acute dyspnoea. Tidsskr Nor Laegeforen. 2003;123(15):2045-8.

Knudsen CW, Riis JS, Finsen AV, et al. Diagnostic value of a rapid test for B-type natriuretic peptide in patients presenting with acute dyspnoea: effect of age and gender. Eur J Heart Fail. 2004;6(1):55-62.

Kozhuharov N, Sabti Z, Wussler D, et al. Prospective validation of N-terminal pro B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. Eur J Heart Fail. 2019;21(6):813-5.

Koulouri S, Acherman RJ, Wong PC, Chan LS, Lewis AB. Utility of B-type natriuretic peptide in differentiating congestive heart failure from lung disease in pediatric patients with respiratory distress. Pediatr Cardiol. 2004;25(4):341-6.

Klemen P, Golub M, Grmec S. Combination of quantitative capnometry, N-terminal pro-brain natriuretic peptide, and clinical assessment in differentiating acute heart failure from pulmonary disease as cause of acute dyspnea in pre-hospital emergency setting: study of diagnostic accuracy. Croat Med J. 2009;50(2):133-42.

Villacorta H, Duarte A, Duarte NM, et al. The role of B-type natriuretic peptide in the diagnosis of congestive heart failure in patients presenting to an emergency department with dyspnea. Arq Bras Cardiol. 2002;79(6):569-72, 4-8.

Lewis LK, Raudsepp SD, Whitlow JC, et al. Assays specific for BNP1-32 and NT-proBNP exhibit a similar performance to two widely used assays in the diagnosis of heart failure. Clin Chem. 2022;68(10):1292-301.

Krishnaswamy P, Lubien E, Clopton P, et al. Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction. Am J Med. 2001;111(4):274-9.

Abdullah A, Iqbal A, Ishtiaq W, Hussain SW, Qadeer A, Rasheed G. Diagnostic utility of N-terminal pro-brain natriuretic peptide and C-reactive protein in diagnosing heart failure in patients with acute hypoxemic respiratory failure. Cureus. 2020;12(1):e6835.

Robaei D, Koe L, Bais R, Gould I, Stewart T, Tofler GH. Effect of NT-proBNP testing on diagnostic certainty in patients admitted to the emergency department with possible heart failure. Annals of Clinical Biochemistry. 2011;48(3):212-7.

Lokuge A, Lam L, Cameron P, et al. B-type natriuretic peptide testing and the accuracy of heart failure diagnosis in the emergency department. Circ Heart Fail. 2010;3(1):104-10.

Su Q, Liu H, Zhang X, et al. Diagnostic values of NT-proBNP in acute dyspnea among elderly patients. International Journal of Clinical and Experimental Pathology. 2015;8(10):13471.

Tung RH, Camargo CA, Jr., Krauser D, et al. Amino-terminal pro-brain natriuretic peptide for the diagnosis of acute heart failure in patients with previous obstructive airway disease. Ann Emerg Med. 2006;48(1):66-74.

van der Burg-de Graauw N, Cobbaert CM, Middelhoff CJ, Bantje TA, van Guldener C. The additive value of N-terminal pro-B-type natriuretic peptide testing at the emergency department in patients with acute dyspnoea. Eur J Intern Med. 2009;20(3):301-6.

Wieshammer S, Dreyhaupt J, Basler B, Marsovszky E. NT-proBNP for pulmonologists: not only a rule-out test for systolic heart failure but also a global marker of heart disease. Respiration. 2009;77(4):370-80.

Yeganeh M, Jaweed SS, Woei KSS, Zakaria MIb, Loch A. Accuracy of B-type natriuretic peptide in a multiethnic Asian population with acute dyspnea. Hong Kong Journal of Emergency Medicine. 2022;29(2):101-7.

Steg PG, Joubin L, McCord J, et al. B-type natriuretic peptide and echocardiographic determination of ejection fraction in the diagnosis of congestive heart failure in patients with acute dyspnea. Chest. 2005;128(1):21-9.