1. BNP in Heart Failure
Azam Hadi MD
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2. Outline BNP physiology Heart failure diagnosis Prognosis
BNP guided therapy
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3. Natural History of Heart Failure
100 75 50 25 I II
III IV 1 10
NYHA CLASS
Annual Survival Rate
Hospitalizations / year .1
Deceased
Class IV
Severe symptoms despite optimal medical therapy
Sharp deterioration in survival
Increase in hospitalizations
This slide demonstrates the importance of treating heart failure in Stage III, since waiting until Stage IV leaves very few options for treatment.
Admission of a heart failure patient to hospital is a warning sign that this patient requires intervention.
Survival Rate
Hospitalizations
Adapted from Bristow, MR Management of Heart Failure, Heart Disease: A Textbook of Cardiovascular Medicine, 7th edition, ed. Braunwald et al.

4. Norepinephrine in HF
Elevated Plasma Norepinephrine Concentration Predicts an Unfavorable Prognosis in Heart Failure Patients
Cohn et.al., 1984

5. Neurohormonal Axis

6. CVP and Cardiac Outcomes
Kaplan-Meier Analysis of Event-Free Survival According to Tertiles of CVP
Damman, K. et al. J Am Coll Cardiol 2009;53:

7. Damman, K. et al. J Am Coll Cardiol 2009;53:582-588
Curvilinear Relationship Between CVP and eGFR According to Different Cardiac Index Values
Solid line = cardiac index <2.5
dashed line = cardiac index 2.5 to 3.2
dotted line = cardiac index >3.2
p =
Central Venous Pressure
Damman, K. et al. J Am Coll Cardiol 2009;53:

8. Physiology
Maisel A et al. Eur J Heart Fail 2008;10:

9. BNP history
1988 – Sudoh et al isolate BNP from porcine tissue (“Brain”)
1991 Mukoyama et al. “cardiac hormone secreted by the ventricles”
1994 Davis et al – BNP in dyspneic patients
2001 Maisel et al. publish the first point of care BNP in ED and hospital setting
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10. Natriuretic peptides

11. BNP half life

12. Natriuretic peptide receptors

13. BNP and diagnosis 1994 – Davis et al.
52 patients with dyspnea admitted from ER.
HF diagnosis by cardiologists blinded to BNP results
Sensitivity 93% Specificity 90%
Breath Not Properly (BNP) trial – Maisel et al. N=1586 patients in a multicenter trial

14. Breath Not Properly ER physicians were blinded to BNP results
Mean age 64±17 Female 44%
Cutoff of BNP=100 pg/ml – sensitivity of 90% and specificity of 76%
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15. Breath Not Properly
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16. Maisel AS et al. N Engl J Med 2002;347:161-167.
Receiver-Operating-Characteristic Curve for Various Cutoff Levels of B-Type Natriuretic Peptide
Figure 3. Receiver-Operating-Characteristic Curve for Various Cutoff Levels of B-Type Natriuretic Peptide (BNP) in Differentiating between Dyspnea Due to Congestive Heart Failure and Dyspnea Due to Other Causes.
Maisel AS et al. N Engl J Med 2002;347:

17. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.
Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting
AJC; Volume 95, Issue 8, 15 April 2005, Pages 948–954

18. BNP nomogram
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19. BNP and Diagnosis
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20. BNP – confounding conditions
Renal failure – elevated BNP. Not only “decreased clearance”
Age and gender – esp. elderly women
Flash pulmonary edema – BNP, unlike ANP, not extensively stored – requires mRNA upregulation
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21. BNP – confounding conditions
Obesity – lowers BNP levels (NPR-C receptors)
RV dysfunction – Pulmonary Embolism, PH
Constriction/Tamponade – BNP not elevated
Diastolic dysfunction – lower BNPs
Sepsis/ICU patient – modestly elevated BNP
Nesiritide or Entresto
Flash pulmonary edema – BNP, unlike ANP, not extensively stored – requires mRNA upregulation
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22. ACC/AHA Guidelines Class 1 Recommendation
Measurement of BNP or NT-proBNP is useful to support clinical judgment for the diagnosis of acutely decompensated HF, especially in the setting of uncertainty for the diagnosis (Level of Evidence: A)
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23. BNP and prognosis
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24. Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure
Kaplan-Meier curves showing the cumulative incidence of death or re-admission according to predischarge B-type natriuretic peptide (BNP) cut-off value of 350 ng/l in the validation study; p =
J Am Coll Cardiol. 2004;43(4): doi: /j.jacc
Date of download:
11/10/2013

25. BNP and prognosis
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26. Val-HeFT (Valsartan Heart Failure Trial)
Prognostic Value of Changes in N-Terminal Pro-Brain Natriuretic Peptide
Val-HeFT (Valsartan Heart Failure Trial)
J Am Coll Cardiol. 2008;52(12): doi: /j.jacc

27. Val-HeFT (Valsartan Heart Failure Trial)
Prognostic Value of Changes in N-Terminal Pro-Brain Natriuretic Peptide
Val-HeFT (Valsartan Heart Failure Trial)
J Am Coll Cardiol. 2008;52(12): doi: /j.jacc

28. BNP and prognosis
Fonarow GC et al. J Am Coll Cardiol 2007; 49(19):
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29. BNP and prognosis
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30. ACC/AHA Guidelines Class 1 Recommendation
Measurement of BNP or NT-proBNP and/or cardiac troponin is useful for establishing prognosis or disease severity in acutely decompensated HF (Level of Evidence: A)
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31. Protect Trial
Patient with Class II-IV symptoms, EF  40%, recent HF event
Randomization echocardiogram
Standard of Care
Minnesota Living With HF Questionnaire quarterly
Standard of Care + NT-proBNP
Therapy adjusted to achieve
optimal drug targets
Visits q3 months
Extra visits as needed for treatment goals
Therapy adjusted to achieve optimal drug targets PLUS NT-proBNP  1000 pg/mL
Close-out echocardiogram
Total cardiovascular events assessed

32. Protect Trial- Office visits
*908 visits overall; mean follow-up 10 ± 3 months
Median number of visits: NT-proBNP 6.0 vs SOC 5.0; P =.05
SOC
NT-proBNP
P = .001
1-4 visits
5 visits
6-7 visits
≥8 visits
Visit number

33. Protect Trial- Primary End Point
SOC
NT-proBNP
100 events
58 events
*Logistic OddsNT-proBNP= 0.44
(95% CI= ; P =.019)
*Adjusted for age, LVEF, NYHA Class, and eGFR

34. Kaplan-Meier Analysis
1.0
Log rank P =.03
0.8
0.6
Event free survival
0.4
Standard-of-care (N=76)
NT-proBNP (N=75)
0.2 73
146
219
292
365
Days from enrollment

35. GUIDE-IT
The aim of the GUIDE-IT study is to randomize approximately 1,100 high-risk patients with chronic HF who have a left ventricular EF ≤40% to either optimized guideline-recommended therapy or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of <1,000 pg/ml. Patients in either arm of the study are followed up at regular intervals and after treatment adjustments for a minimum of 12 months

36. BNP guided therapy
Serial BNPs still controversial, but increasingly used…
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37. ACC/AHA Guidelines Class IIa Recommendation
BNP or NT-ProBNP guided therapy is useful to achieve optimal dosing of GDMT in select clinically euvolemic patients followed in a well structured HF disease management program (Level of evidence: B)
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38. Conclusions BNP is a very useful diagnostic test
Use clinical assessment along with BNP – not clinical assessment versus BNP…
Trending BNP for a specific patient is more accurate than the absolute value itself
Pre-discharge BNP is helpful
Serial BNPs for management/decisions
(obesity, critically ill, heart transplant patients, renal failure)
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