The talk describes the utility and limitations of Brain Natriuretic peptide (BNP) and N-terminal proBNP (NT-pBNP) in the clinical management of heart failure

1. ESCBM meeting 2018, Prague
Utility of Cardiac Biomarkers in
Clinical Heart Failure Care
Md. Shahidul Islam, M.D., Ph.D
shaisl@me.com

2. 2

3. 3

4. 4
Circulating Biomarkers in Heart
Failure. Berezin AE. Adv. Exp.
Med. Biol. 2018
Evolving Role of Natriuretic
Peptides from Diagnostic Tool to
Therapeutic Modality. Pagel-
Langenickel I. Adv. Exp. Med.
Biol. 2018

6. 6

7. 7

8. Plasma BNP concentration in patients with and without left
ventricular systolic dysfunction. McDonagh TA et al, 1998,
Lancet 351:9

9. BNP and NT-pBNP
 Similar concentration in normal people
 In LV dysfunction NT-pBNP is about four times higher than BNP

10. Variations in the concentrations of BNP and
NT-pBNP
Age:
Normal values increase with age
Sex:
Higher in women
BMI:
Lower in obese people
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11. Cutoffs of NT-pBNP for diagnosis of HF
 Age < 50 years: 450 ng/l
 Age 50-75 years: 900 ng/l
 Age > 75 years: 18000 ng/l
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12. Rapid measurement of BNP in rapid diagnosis of heart failure
Maisel AS et al, NEJM, 2002; 347:161

13. Usefuleness of NT-pBNP in primary care settings
Wright SP et al J Am Coll Cardiol 2003; 42:1793

14. Kaplan-Meier analysis of cumulative rates of survival in CHF patients with
eft ventricular dysfunction stratified into two groups on the basis of
median plasma concentration (73 pg/mL) of BNP.
Takayoshi Tsutamoto et al. Circulation. 1997;96:509-516
Copyright © American Heart Association, Inc. All rights reserved.

15. Plasma BNP concentration predicts survival in
Heart failure patients. Anand IS et al 2003, Circulation,
107:1278

16. Hartmann F et al 2004 Circulation 110:1780
One year mortality 7%
One year mortality 21.6%

17. Hartmann F et al 2004 Circulation 110:1780
2.5 fold higher risk of
death or hospitalization

18. BNP or NT-pBNP?
No accepted conversion factor
BNP >100 ng/l is roughly equivalent to
NT-pBNP > 900 ng/l for HF diagnosis
NT-pBNP has greater prognostic value
NT-pBNP is more sensitive to renal function
NT-pBNP is useful during treatment with ARNI
or neseritide
NT-pBNP and BNP assays probably detect proBNP

19. Variability of BNP and NT-pBNP
 Intraindividual biologic variatian and analytic assay variation
 Significant difference in results over time depends on the total
variability (RCV percentage change, or Relative Change Value)
 Significant change for NT-pBNP: 11% decrease in day do day
values, or 47% decrease in week to week values
 Significant change for BNP: 25% decrease in day do day
values, or 72% decrease in week to week values
 Wu AH et al, Am Heart J 2006; 152:828
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20. Disadvantages of BNP / NT-pBNP
 A high NP doesn not exclude other co-exixting diseases
 NPs do not increase in some acute HF
 Some patients with severe chronic HF have high NP
 Right heart failure due to lung disease or left ventricular disease
 have high NPs
 NP measurement must be combined with clinical assessment
 Special case for people treated with nesiritide or sacubritil
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21. NT-pBNP in patients with renal failure
 NT-pBNP is excreted by the kidney
 Cut-off values in patients with GFR <60 ml/min:
 >1200 ng/l
 Cut-off values in patients with GFR >60 ml/min:
 >450 ng/l for patients < 50 years
 >900 ng/l for patients > 50 years
In patients with GFR > 60, sensitivity 85%, specificity 88%; In patients
with GFR <60 sensitivity 89%, specificity 72%
Anwaruddin, S et al, J Am Coll Cardiol 2006; 47:91
21

22. Value of serial NT-pBNP guided therapy
Not useful in acute HF
In chronic HF the results are mixed
NT-pBNP guided therapy reduces mortality in patients
< 75 years.
NT-pBNP guided therapy helps achieving target dose
of ACE-I and beta blockers in patients < 75 years
Porapakkham P et al Arch Intern Med 2010; 170:507
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23. 2010 201
3
201
4
201
6
201
7
0
3000
500
1000
1500
2000
2500
BNP(ng/L)
We
t
Dry
201
5
HF hospitalization
Worsening
HF
Worsening
HF
Time-course of B-type natriuretic peptide levels in a patient with heart
failure with reduced left ventricular ejection fraction.

24. 0
,2
,4
,6
,8
1
Cum.Survival
0 25 50 75 100 125 150 175 200
Time (months)
High BNP and high E/e’
High BNP and Low E/e’
Low BNP and low E/e’
P < 0.0001
Low BNP and High E/e’
All-cause mortality in patients with chronic heart failure categorized according to B-
type natriuretic peptide (BNP) levels and the ratio of transmitral blood flow to
myocardial early diastolic velocities (E/e’). Simioniuc A et al, Int J Cardiol
2016;224:416-423

26. 26
PARADIGM Study. McMurray JJ et al. NEJM 2014, 371:993