Brain natriuretic peptide 32 explained

Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume.^[1] BNP is one of the three natriuretic peptides, in addition to ANP and CNP.^[2]

The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid N-terminal fragment in the prohormone called NT-proBNP (BNPT), which is biologically inactive. Once released, BNP binds to and activates the atrial natriuretic factor receptor NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.

The physiologic actions of BNP are similar to those of ANP and include decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. The net effect of these peptides is a decrease in blood pressure due to the decrease in systemic vascular resistance and, thus, afterload. Additionally, the actions of both BNP and ANP result in a decrease in cardiac output due to an overall decrease in central venous pressure and preload as a result of the reduction in blood volume that follows natriuresis and diuresis.^[3]

Biosynthesis

BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 25-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked glycoprotein; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably furin or corin) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts.^[4] Cleavage at other sites produces shorter BNP peptides with unknown biological activity.^[5] Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.^[6] The synthesis of BNP in cardiomyocytes is stimulated by pro-inflammatory cell factors, such as interleukin-1β, interleukin-6 and tumor necrosis factor-α.^[7]

Physiologic effects

Renal

• Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases pressure in the glomerular capillaries, thus increasing the glomerular filtration rate (GFR), resulting in greater filter load of sodium and water.
• Increases blood flow through the vasa recta, which will wash the solutes (NaCl and urea) out of the medullary interstitium.^[8] The lower osmolarity of the medullary interstitium leads to less reabsorption of tubular fluid and increased excretion.
• Decreases sodium reabsorption in the distal convoluted tubule (interaction with NCC)^[9] and cortical collecting duct of the nephron via guanosine 3',5'-cyclic monophosphate (cGMP) dependent phosphorylation of ENaC.
• Inhibits renin secretion, thereby inhibiting the renin–angiotensin–aldosterone system.

Adrenal

• Reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex.

Vascular

Relaxes vascular smooth muscle in arterioles and venules by:

• Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
• Inhibition of the effects of catecholamines

Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension.^[10]

Cardiac

• Inhibits maladaptive cardiac hypertrophy
• Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly^[11]
• Re-expression of NPRA rescues the phenotype.

Adipose tissue

• Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
• Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
• Increases intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP-dependent protein kinase-I (cGK-I)
• Does not modulate cAMP production or PKA activity

Measurement

BNP and NT-proBNP are measured by immunoassay.^[12]

Interpretation of BNP

• The main clinical utility of either BNP or NT-proBNP is that a normal level helps to rule out chronic heart failure in the emergency setting. An elevated BNP or NT-proBNP should never be used exclusively to "rule in" acute or chronic heart failure in the emergency setting due to lack of specificity .^[13]
• Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.^[14]
• Increased NT-proBNP adjusted for age and sex and annual increase of NT-proBNP above 50% are associated with increased event rate in patients with non-severe aortic valve stenosis.^[15]
• BNP and NT-proBNP are also typically increased in patients with left ventricular dysfunction, with or without symptoms (BNP accurately reflects current ventricular status, as its half-life is 20 minutes, as opposed to 1–2 hours for NT-proBNP).^[16]

A preoperative BNP can be predictive of a risk of an acute cardiac event during vascular surgery. A cutoff of 100 pg/ml has a sensitivity of approximately 100%, a negative predictive value of approximately 100%, a specificity of 90%, and a positive predictive value of 78% according to data from the United Kingdom.^[17]

BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The achilles heel of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population.^{[18] [19]}

Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/mL

There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be an indicator of heart failure. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis.^{[20] [21]}

BNP has been suggested as a predictor for a variety of medical states, including cardiovascular mortality in diabetics^[22] and cardiac impairment in cancer patients.^{[23] [24]}

BNP was found to have an important role in prognostication of heart surgery patients^[25] and in the emergency department.^[26] Bhalla et al. showed that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies.^{[27] [28]} Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and ESRD.^{[29] [30] [31]}

The effect or race and gender on value of BNP and its utility in that context has been studied extensively.^{[32] [33]}

NT-proBNP levels (in pg/mL) by NYHA functional class^[34] ! !! NYHA I !! NYHA II !! NYHA III !! NYHA IV

5th Percentile	33	103	126	148
Mean	1015	1666	3029	3465
95th Percentile	3410	6567	10,449	12,188

The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive.^[35] The BNP test is also used for the risk stratification of patients with acute coronary syndromes.^{[36] [37]}

When interpreting an elevated BNP level, values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.^[38] Higher levels are seen in those with renal disease, in the absence of heart failure.

Therapeutic application

Recombinant BNP, nesiritide, has been suggested as a treatment for decompensated heart failure. However, a clinical trial failed to show a benefit of nesiritide in patients with acute decompensated heart failure.^[39] Blockade of neprilysin, a protease known to degrade members of the natriuretic peptide family, has also been suggested as a possible treatment for heart failure. Dual administration of neprilysin inhibitors and angiotensin receptor blockers has been shown to be advantageous to ACE inhibitors, the current first-line therapy, in multiple settings.^{[40] [41]}

Further reading

• Cosson S . Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus . Diabetes & Metabolism . 30 . 4 . 381–6 . September 2004 . 15525883 . 10.1016/S1262-3636(07)70132-5 .
• Cauliez B, Berthe MC, Lavoinne A . [Brain natriuretic peptide: physiological, biological and clinical aspects] . Annales de Biologie Clinique . 63 . 1 . 15–25 . 2005 . 15689309 .
• Buchner S, Riegger G, Luchner A . [Clinical utility of the cardiac markers BNP and NT-proBNP] . Acta Medica Austriaca . 31 . 4 . 144–51 . 2005 . 15732251 .
• LaPointe MC . Molecular regulation of the brain natriuretic peptide gene . Peptides . 26 . 6 . 944–56 . June 2005 . 15911064 . 10.1016/j.peptides.2004.08.028 . 38061760 .
• Hoffmann U, Borggrefe M, Brueckmann M . New horizons: NT-proBNP for risk stratification of patients with shock in the intensive care unit . Critical Care . 10 . 2 . 134 . 2006 . 16594987 . 1550883 . 10.1186/cc4883 . free .
• Suga S, Nakao K, Hosoda K, Mukoyama M, Ogawa Y, Shirakami G, Arai H, Saito Y, Kambayashi Y, Inouye K . Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide . Endocrinology . 130 . 1 . 229–39 . January 1992 . 1309330 . 10.1210/endo.130.1.1309330 . free .
• Kambayashi Y, Nakao K, Mukoyama M, Saito Y, Ogawa Y, Shiono S, Inouye K, Yoshida N, Imura H . Isolation and sequence determination of human brain natriuretic peptide in human atrium . FEBS Letters . 259 . 2 . 341–5 . January 1990 . 2136732 . 10.1016/0014-5793(90)80043-I . free .
• Hino J, Tateyama H, Minamino N, Kangawa K, Matsuo H . Isolation and identification of human brain natriuretic peptides in cardiac atrium . Biochemical and Biophysical Research Communications . 167 . 2 . 693–700 . March 1990 . 2138890 . 10.1016/0006-291X(90)92081-A .
• Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H . Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide . Biochemical and Biophysical Research Communications . 159 . 3 . 1427–34 . March 1989 . 2522777 . 10.1016/0006-291X(89)92269-9 .
• Seilhamer JJ, Arfsten A, Miller JA, Lundquist P, Scarborough RM, Lewicki JA, Porter JG . Human and canine gene homologs of porcine brain natriuretic peptide . Biochemical and Biophysical Research Communications . 165 . 2 . 650–8 . December 1989 . 2597152 . 10.1016/S0006-291X(89)80015-4 .
• Arden KC, Viars CS, Weiss S, Argentin S, Nemer M . Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36 . Genomics . 26 . 2 . 385–9 . March 1995 . 7601467 . 10.1016/0888-7543(95)80225-B .
• Weir ML, Pang SC, Flynn TG . Characterization of binding sites in rat for A, B and C-type natriuretic peptides . Regulatory Peptides . 47 . 3 . 291–305 . September 1993 . 7901875 . 10.1016/0167-0115(93)90396-P . 23098254 .
• Totsune K, Takahashi K, Satoh F, Sone M, Ohneda M, Satoh C, Murakami O, Mouri T . Urinary immunoreactive brain natriuretic peptide in patients with renal disease . Regulatory Peptides . 63 . 2–3 . 141–7 . July 1996 . 8837222 . 10.1016/0167-0115(96)00035-3 . 23508808 .
• Totsune K, Takahashi K, Murakami O, Satoh F, Sone M, Ohneda M, Miura Y, Mouri T . Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors . European Journal of Endocrinology . 135 . 3 . 352–6 . September 1996 . 8890728 . 10.1530/eje.0.1350352 . 8706854 .
• Matsuo K, Nishikimi T, Yutani C, Kurita T, Shimizu W, Taguchi A, Suyama K, Aihara N, Kamakura S, Kangawa K, Takamiya M, Shimomura K . Diagnostic value of plasma levels of brain natriuretic peptide in arrhythmogenic right ventricular dysplasia . Circulation . 98 . 22 . 2433–40 . December 1998 . 9832489 . 10.1161/01.CIR.98.22.2433 . free .
• Wiese S, Breyer T, Dragu A, Wakili R, Burkard T, Schmidt-Schweda S, Füchtbauer EM, Dohrmann U, Beyersdorf F, Radicke D, Holubarsch CJ . Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length . Circulation . 102 . 25 . 3074–9 . December 2000 . 11120697 . 10.1161/01.CIR.102.25.3074 . free .
• Shimizu H, Masuta K, Aono K, Asada H, Sasakura K, Tamaki M, Sugita K, Yamada K . Molecular forms of human brain natriuretic peptide in plasma . Clinica Chimica Acta; International Journal of Clinical Chemistry . 316 . 1–2 . 129–35 . February 2002 . 11750283 . 10.1016/S0009-8981(01)00745-8 .
• Ogawa K, Oida A, Sugimura H, Kaneko N, Nogi N, Hasumi M, Numao T, Nagao I, Mori S . Clinical significance of blood brain natriuretic peptide level measurement in the detection of heart disease in untreated outpatients: comparison of electrocardiography, chest radiography and echocardiography . Circulation Journal . 66 . 2 . 122–6 . February 2002 . 11999635 . 10.1253/circj.66.122 . free .
• Asakawa H, Fukui T, Tokunaga K, Kawakami F . Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria . Journal of Diabetes and Its Complications . 16 . 3 . 209–13 . 2002 . 12015190 . 10.1016/S1056-8727(01)00173-8 .
• Bordenave L, Georges A, Bareille R, Conrad V, Villars F, Amédée J . Human bone marrow endothelial cells: a new identified source of B-type natriuretic peptide . Peptides . 23 . 5 . 935–40 . May 2002 . 12084525 . 10.1016/S0196-9781(02)00004-9 . 43543051 .

External links

• • BNP and NT-proBNP at Lab Tests Online

attribution: copied from Brain natriuretic peptide version as of 13:57, 4 December 2019

Notes and References

1. Book: Potter . LR . Yoder . AR . Flora . DR . Antos . LK . Dickey . DM . Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. . Handbook of Experimental Pharmacology . 2009 . 191 . 191 . 341–66 . 10.1007/978-3-540-68964-5_15 . 19089336. 4855512 . 978-3-540-68960-7 .
2. Book: Potter . Lincoln R. . Yoder . Andrea R. . Flora . Darcy R. . Antos . Laura K. . Dickey . Deborah M. . Natriuretic Peptides: Their Structures, Receptors, Physiologic Functions and Therapeutic Applications . Handbook of Experimental Pharmacology . 2009 . CGMP: Generators, Effectors and Therapeutic Implications . 191 . 191 . 341–366 . 10.1007/978-3-540-68964-5_15 . 0171-2004 . 4855512 . 19089336. 978-3-540-68960-7 .
3. Web site: CV Pharmacology - Natriuretic Peptides. cvpharmacology.com. 29 April 2018. dead. https://web.archive.org/web/20171021200256/http://cvpharmacology.com/diuretic/natriuretics. 21 October 2017.
4. Schellenberger U, O'Rear J, Guzzetta A, Jue RA, Protter AA, Pollitt NS . The precursor to B-type natriuretic peptide is an O-linked glycoprotein . Archives of Biochemistry and Biophysics . 451 . 2 . 160–6 . July 2006 . 16750161 . 10.1016/j.abb.2006.03.028 .
5. Niederkofler EE, Kiernan UA, O'Rear J, Menon S, Saghir S, Protter AA, Nelson RW, Schellenberger U . Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure . Circulation: Heart Failure . 1 . 4 . 258–64 . November 2008 . 19808300 . 10.1161/CIRCHEARTFAILURE.108.790774 . free .
6. Semenov AG, Postnikov AB, Tamm NN, Seferian KR, Karpova NS, Bloshchitsyna MN, Koshkina EV, Krasnoselsky MI, Serebryanaya DV, Katrukha AG . Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site . Clinical Chemistry . 55 . 3 . 489–98 . March 2009 . 19168558 . 10.1373/clinchem.2008.113373 . free .
7. Fu . Shihui . Ping . Ping . Wang . Fengqi . Luo . Leiming . Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure . Journal of Biological Engineering . December 2018 . 12 . 1 . 2 . 10.1186/s13036-017-0093-0 . 29344085 . 5766980 . free .
8. Kiberd BA, Larson TS, Robertson CR, Jamison RL . Effect of atrial natriuretic peptide on vasa recta blood flow in the rat . The American Journal of Physiology . 252 . 6 Pt 2 . F1112-7 . June 1987 . 2954471 . 10.1152/ajprenal.1987.252.6.F1112 .
9. Book: Reeves WB, Andreoli TE . Giebisch GH, Alpern RA, Herbert SC, Seldin DW . Seldin and Giebisch's the kidney: physiology and pathophysiology . limited . Elsevier/Academic Press . Amsterdam . 2008 . 849–887. 978-0-12-088488-9 . Chapter 31 – Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct . 10.1016/B978-012088488-9.50034-6 .
10. Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, Huang X, Liu M, Fang C, Peng J, Chen S, Wu S, Liu Z, Dong L, Zhou Y, Wu Q . Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy . Nature . 484 . 7393 . 246–50 . March 2012 . 22437503 . 3578422 . 10.1038/nature10897 . 2012Natur.484..246C .
11. Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, Kasahara M, Hashimoto R, Katsuura G, Mukoyama M, Itoh H, Saito Y, Tanaka I, Otani H, Katsuki M . Cardiac fibrosis in mice lacking brain natriuretic peptide . Proceedings of the National Academy of Sciences of the United States of America . 97 . 8 . 4239–44 . April 2000 . 10737768 . 18212 . 10.1073/pnas.070371497 . 2000PNAS...97.4239T . free .
12. Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, Zucchelli GC, Plebani M . State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study . Clinica Chimica Acta; International Journal of Clinical Chemistry . 414 . 112–9 . December 2012 . 22910582 . 10.1016/j.cca.2012.07.017 . 11382/365432 . free .
13. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA . Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure . The New England Journal of Medicine . 347 . 3 . 161–7 . July 2002 . 12124404 . 10.1056/NEJMoa020233 . free .
14. Bhalla V, Willis S, Maisel AS . B-type natriuretic peptide: the level and the drug--partners in the diagnosis of congestive heart failure . Congestive Heart Failure . 10 . 1 Suppl 1 . 3–27 . 2004 . 14872150 . 10.1111/j.1527-5299.2004.03310.x . free .
15. Hadziselimovic . Edina . Greve . Anders M. . Sajadieh . Ahmad . Olsen . Michael H. . Kesäniemi . Y. Antero . Nienaber . Christoph A. . Ray . Simon G. . Rossebø . Anne B. . Willenheimer . Ronnie . Wachtell . Kristian . Nielsen . Olav W. . 2022-04-01 . Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial . JAMA Cardiology . en . 7 . 4 . 435–444 . 10.1001/jamacardio.2021.5916 . 2380-6583 . 8851368 . 35171199.
16. Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS . A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction . American Heart Journal . 148 . 3 . 518–23 . September 2004 . 15389242 . 10.1016/j.ahj.2004.03.014 .
17. Berry C, Kingsmore D, Gibson S, Hole D, Morton JJ, Byrne D, Dargie HJ . Predictive value of plasma brain natriuretic peptide for cardiac outcome after vascular surgery . Heart . 92 . 3 . 401–2 . March 2006 . 16501204 . 1860808 . 10.1136/hrt.2005.060988 .
18. Austin WJ, Bhalla V, Hernandez-Arce I, Isakson SR, Beede J, Clopton P, Maisel AS, Fitzgerald RL . Correlation and prognostic utility of B-type natriuretic peptide and its amino-terminal fragment in patients with chronic kidney disease . American Journal of Clinical Pathology . 126 . 4 . 506–12 . October 2006 . 16938661 . 10.1309/M7AAXA0J1THMNCDF . free .
19. Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Maisel AS . How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study . American Heart Journal . 151 . 5 . 999–1005 . May 2006 . 16644321 . 10.1016/j.ahj.2005.10.011 .
20. Strunk A, Bhalla V, Clopton P, Nowak RM, McCord J, Hollander JE, Duc P, Storrow AB, Abraham WT, Wu AH, Steg G, Perez A, Kazanegra R, Herrmann HC, Aumont MC, McCullough PA, Maisel A . 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 . 119 . 1 . 69.e1–11 . January 2006 . 16431187 . 10.1016/j.amjmed.2005.04.029 . free .
21. Brenden CK, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R, Maisel AS . Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study . American Heart Journal . 151 . 5 . 1006–11 . May 2006 . 16644322 . 10.1016/j.ahj.2005.10.017 .
22. Bhalla MA, Chiang A, Epshteyn VA, Kazanegra R, Bhalla V, Clopton P, Krishnaswamy P, Morrison LK, Chiu A, Gardetto N, Mudaliar S, Edelman SV, Henry RR, Maisel AS . Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus . Journal of the American College of Cardiology . 44 . 5 . 1047–52 . September 2004 . 15337217 . 10.1016/j.jacc.2004.05.071 . free .
23. Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study . Palumbo . I. . Palumbo . B. . Fravolino . M.L. . etal . The Breast . 25 . 45–50 . 2016 . 26547836 . 10.1016/j.breast.2015.10.004.
24. Plasma brain natriuretic peptide levels are elevated in patients with cancer . Bando . S. . Soeki . T. . Matsuura . T. . etal . 10.1371/journal.pone.0178607 . 28570595 . PLOS ONE . 2017 . 12 . 6 . e0178607. 5453551 . 2017PLoSO..1278607B . free .
25. Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS . Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery . Journal of the American College of Cardiology . 43 . 10 . 1873–9 . May 2004 . 15145114 . 10.1016/j.jacc.2003.12.048 . free .
26. Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R . Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath . Journal of the American College of Cardiology . 44 . 6 . 1328–33 . September 2004 . 15364340 . 10.1016/j.jacc.2004.06.015 . free .
27. Bhalla V, Isakson S, Bhalla MA, Lin JP, Clopton P, Gardetto N, Maisel AS . Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients . American Journal of Hypertension . 18 . 2 Pt 2 . 73S–81S . February 2005 . 15752936 . 10.1016/j.amjhyper.2004.11.044 . free .
28. Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS . B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events . Journal of Cardiac Failure . 15 . 1 . 41–7 . February 2009 . 19181293 . 10.1016/j.cardfail.2008.09.003 .
29. Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A . Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women . American Journal of Obstetrics and Gynecology . 193 . 2 . 450–4 . August 2005 . 16098869 . 10.1016/j.ajog.2004.12.006 .
30. Bhalla V, Bhalla MA, Maisel AS . Evolution of B-type natriuretic peptide in evaluation of intensive care unit shock . Critical Care Medicine . 32 . 8 . 1787–9 . August 2004 . 15286561 . 10.1097/01.CCM.0000135748.75590.54 .
31. Sheen V, Bhalla V, Tulua-Tata A, Bhalla MA, Weiss D, Chiu A, Abdeen O, Mullaney S, Maisel A . The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease . American Heart Journal . 153 . 2 . 244.e1–5 . February 2007 . 17239684 . 10.1016/j.ahj.2006.10.041 .
32. Maisel AS, Clopton P, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Steg G, Westheim A, Knudsen CW, Perez A, Kazanegra R, Bhalla V, Herrmann HC, Aumont MC, McCullough PA . Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study . American Heart Journal . 147 . 6 . 1078–84 . June 2004 . 15199359 . 10.1016/j.ahj.2004.01.013 .
33. Daniels LB, Bhalla V, Clopton P, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Jesse R, Maisel A . B-type natriuretic peptide (BNP) levels and ethnic disparities in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision making in patients presenting with shortness of breath . Journal of Cardiac Failure . 12 . 4 . 281–5 . May 2006 . 16679261 . 10.1016/j.cardfail.2006.01.008 .
34. Encyclopedia: N-terminal-pro-BNP . The University of Iowa (UIHC), Department of Pathology. LABORATORY SERVICES HANDBOOK. 28 May 2020 . live. https://web.archive.org/web/20081011225930/http://www.medicine.uiowa.edu/Path_Handbook/handbook/test2621.html . 2008-10-11. Showing 95th percentiles. Epic Lab Code: LAB649.
35. Lam LL, Cameron PA, Schneider HG, Abramson MJ, Müller C, Krum H . Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting . Annals of Internal Medicine . 153 . 11 . 728–35 . December 2010 . 21135296 . 10.7326/0003-4819-153-11-201012070-00006 . 27272593 .
36. Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA . N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease . JAMA . 297 . 2 . 169–76 . January 2007 . 17213400 . 2848442 . 10.1001/jama.297.2.169 .
37. Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, Maisel AS . Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure . American Heart Journal . 150 . 3 . 471–7 . September 2005 . 16169326 . 10.1016/j.ahj.2004.11.021 .
38. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS . Impact of obesity on plasma natriuretic peptide levels . Circulation . 109 . 5 . 594–600 . February 2004 . 14769680 . 10.1161/01.CIR.0000112582.16683.EA . 10.1.1.541.9955 . 13454777 .
39. O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ, Rouleau JL, Swedberg K, Adams KF, Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalán R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Méndez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Wilson WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM . Effect of nesiritide in patients with acute decompensated heart failure . The New England Journal of Medicine . 365 . 1 . 32–43 . July 2011 . 21732835 . 10.1056/NEJMoa1100171 . 11379/60663 . free .
40. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR . Angiotensin-neprilysin inhibition versus enalapril in heart failure . The New England Journal of Medicine . 371 . 11 . 993–1004 . September 2014 . 25176015 . 10.1056/NEJMoa1409077 . 10993/27659. 11383 . free.
41. Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E . Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure . The New England Journal of Medicine . 380 . 6 . 539–548 . February 2019 . 30415601 . 10.1056/NEJMoa1812851 . free .