Heart failure (HF) is a complex clinical syndrome affecting 6.2 million people in the United States [1]. The diagnosis of heart failure is challenging as patients usually present non-specific symptoms, which are often shared by other diseases. Both B-type natriuretic peptide (BNP) and the N-terminal pro BNP (NT-proBNP) are widely used as biomarkers to diagnose heart failure and assess a patient’s response to therapy. Cardiomyocytes secrete proBNP in response to myocardial wall stretch, which is further cleaved into two circulating fragments; C-terminal B-type NP (BNP), a biologically active fragment and N-terminal proBNP (NT-proBNP), biologically inactive fragment [2].
NT-proBNP
For treating heart failure, a new FDA approved drug called Entresto is commonly used, which disrupts the levels of BNP [3]. To resolve this issue, NT-proBNP can be used as a biomarker for diagnosis and prognosis in patients treated with Entresto [4]. The pharmacodynamic studies revealed that Entresto increased the plasma levels of BNP, while decreased the plasma levels of NT-proBNP. These increased BNP levels may lead to misinterpretations in the response of patients after treatment with Entresto [5]. Thus NT-proBNP is a better biomarker than BNP. In order to distinguish normal NT-proBNP from the pathological one, different classification systems are used. The classification system provided by the European Society of Cardiology is based on a cut‐off level of 125 ng/L for NT-proBNP in case of chronic heart failure [6]. The classification system provided by Stämpfli et al. is based on age and gender [7]. Clinical Chemistry and Laboratory Medicine use a classification system according to the manufacturer’s instructions [8].
Advantages of NT-proBNP VS BNP
The production of ventricular NT-proBNP has been reported to be upregulated in cardiac failure and localized in the area of myocardial infarct. Half-life and the plasma levels of NT-proBNP is higher than BNP, which may provide a better diagnostic value [9]. Moreover, NT-proBNP is a more stable specimen for diagnosis purposes as it is less likely to degrade in vitro and in vivo [10]. Whereas, BNP has shown less stability in the in vitro studies [11]. All NT-proBNP diagnostic tests are harmonized to the Roche method in contrast to BNP tests, which utilize many targets and antibodies. The BNP testing is not harmonized to a single method, thus yielding different results [12]. NT-proBNP has also shown good results in predicting morbidity, mortality, and hospitalization for HF as compared to BNP [13]. In addition, NT-proBNP has better accuracy in identifying mild HF than BNP [14].
In the past, BNP was the only diagnostic tool for acute HF and ventricular dysfunction [15]. High levels of BNP also act as a predictor for thromboembolism in patients with pulmonary embolism [16]. However, recent developments in research reported the production of NT-proBNP also from the atrial wall upon myocardial stretch [17]. Atrial fibrillation (AF) is associated with alterations in atrial muscle tone, and may lead to generate changes in the production of NT-proBNP. Thus, NT-proBNP can also be used as a risk factor of atrial fibrillation with or without left atrial enlargement [18]. High levels of NT-proBNP are used to distinguish cardiac from the pulmonary causes of acute HF [19], predict short-term and long-term cardiovascular mortality and ischemic recurrence [20], and also used to assess the severity of chronic HF [21]. Levels of NT-proBNP are also used as an effective indicators in predicting cardiac events in elderly chronic heart failure (CHF) and have a clinical significance in evaluating disease severity and prognosis. NT-proBNP detection has a significant role in evaluating CHF in elderly patients [22]. As the plasma level of NT-proBNP is not affected by the medication, thus it has been concluded that NT-proBNP is a better natriuretic biomarker than BNP for HF diagnosis and prognosis.
The RAMP® NT-proBNP test is used in diagnosis and assessment of severity in patients with chronic heart failure.
REFERENCES
1] Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-596.
2] Burnett JC Jr, Kao PC, Hu DC, Heser DW, Heublein D, Granger JP, Opgenorth TJ, Reeder GS. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 1986;231:1145–1147. doi: 10.1126/science.2935937
3] Novartis’new heart failure medicine LCZ696, now called Entresto(TM), approved by FDA to reduce risk of cardiovascular death and heart failure hospitalization. Novartis Press Release. 07 July 2015.
4] Langenickel TH, Dole WP. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discovery Today: Therapeutic Strategies. Vol. 9, No. 4, 2012; e131-e139.
5] ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2015
6] Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González‐Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37: 2129–2200.
7] Stämpfli SF, Erhart L, Hagenbuch N, Stähli BE, Gruner C, Greutmann M, Niemann M, Kaufmann BA, Jenni R, Held L, Tanner FC. Prognostic power of NT‐proBNP in left ventricular
non‐compaction cardiomyopathy. Int J Cardiol 2017; 236: 321–327.
8] Analytics M. COBAS proBNP II. 2016;V 9.0.
9] O’Donoghue M, Chen A, Baggish AL, et al. The effects of ejection fraction on N‐terminal Pro BNP and BNP levels in patients with acute CHF: analysis from the Pro BNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. J Card Fail. 2005;11(5): S9‐S14.
10] Clerico A, Emdin M. Diagnostic accuracy and prognostic relevance of the measurement of cardiac natriuretic peptides: a review. Clin Chem. 2004;50:33–50. doi:10.1373/clinchem.2003.024760.
11] Shimizu H, Aono K, Masuta K, Asada H, Misaki A, Teraoka H. Degradation of human brain natriuretic peptide (BNP) by contact activation of blood coagulation system. Clin Chim Acta. 2001;305:181–186.
12] Melanson SEF, Lewandrowski EL. Laboratory testing for B-type natriuretic peptides (BNP and NT-proBNP): clinical usefulness, utilization, and impact on hospital operations. Am J Clin Pathol. 2005;124 Suppl:S122–S128.
13] Masson S, Latini R, Anand IS, et al. Direct comparison of B-type natriuretic peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data. Clin Chem. 2006; 52:1528–1538. doi:10.1373/clinchem.2006.069575.
14] Emdin M, Passino C, Prontera C, et al. Comparison of brain natriuretic peptide (BNP) and amino-terminal ProBNP for early diagnosis of heart failure. Clin Chem. 2007;53:1289–1297. doi:10.1373/clinchem.2006.080234
15] Maalouf R, Bailey S. A review on B‐type natriuretic peptide monitoring: assays and biosensors. Heart Fail Rev. 2016;21(5):567‐578.
16] Kawabata M, Goya M, Sasaki T, et al. Left atrial appendage thrombi formation in Japanese non‐valvular atrial fibrillation patients during anticoagulation therapy: warfarin vs. direct oral anticoagulants. Circ J. 2017;81(5):645‐651.
17] Inoue S, Murakami Y, Sano K, Katoh H, Shimada T. Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation. J Card Fail. 2000;6(2):92‐96.
18] Zhao, X., Li, H., Liu, C., Ren, Y., & Sun, C. (2022). NT Pro-BNP can be used as a risk predictor of clinical atrial fibrillation with or without left atrial enlargement. Clinical cardiology, 45(1), 68–74. https://doi.org/10.1002/clc.23760
19] Nielsen LS, Svanegaard J, Klitgaard NA, Egeblad H. N-terminal pro-brain natriuretic peptide for discriminating between cardiac and non-cardiac dyspnoea. Eur J Heart Fail 2004; 6: 63–70
20] Morrow DA, de Lemos JA, Sabatine MS et al. Evaluation of B-type natriuretic peptide for risk assessment in Unstable Angina/Non–ST elevation myocardial infarction: B-type natriuretic peptide and prognosis in TAC TICS-TIMI 18. J Am Coll Cardiol 2003; 41: 1264–1272
21] Maisel AS, Krishnaswamy P, Nowak RM et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002; 347: 161–167
22] Shi, L., Zhang, Y., Zhang, J., Gao, Y., Liu, J., Chen, M., & Yang, X. (2020). Application of blood pre-albumin and NT-pro BNP levels in evaluating prognosis of elderly chronic heart failure patients. Experimental and therapeutic medicine, 20(2), 1337–1342. https://doi.org/10.3892/etm.2020.8865