Assessing Congestion in HF : Natriuretic Peptides

1. Assessing Congestion in HF:
Natriuretic Peptides
Michael Felker, MD, MHS, FACC, FAHA
Professor of Medicine
Chief, Heart Failure Section
Duke University School of Medicine

2. Vicious Cycle of Congestion in AHF
Worsening
heart
failure
Elevated
LVEDP
Increased
wall stress
Myocardial
Oxygen
demand
Myocardial
ischemia
Increased functional MR
CONGESTION

3. “If you wish to converse with me, define your terms.”
Voltaire

4. Congestion
• All agree that it is important
• All agree that addressing it is key to success
• What is it exactly?
– Clinical congestion (rales, JVP, edema)?
– Hemodynamic congestion (elevated filling pressures)?
– Something else (fluid loss, body weight change, NP’s)?

5. Pharmacologic Actions of hBNP
Hemodynamic
(balanced vasodilation)
veins
arteries
coronary arteries
Neurohumoral
aldosterone
endothelin
norepinephrine
Renal
diuresis
natriuresis
GFR
D
R I
M
K
R
G
S S
S
S
G
L
G
F
C CS S
G
SGQVM
K V L R
R
H
KPS
Cardiac
lusitropic
antifibrotic
anti-remodeling

6. BNP Correlates (Loosely) with LV Filling Pressures
Kazanegra J, Cardiac Failure 2001
PAW(mmHg)
Hours
BNP(pg/ml)
15
17
19
21
23
25
27
29
31
33
baseline4 8 12 16 20 24
600
700
800
900
1000
1100
1200
1300
PAW
BNP
*Pulmonary artery wedge.

7. BNP Reflects Ventricular Wall Stress
Iwananga, JACC

8. Natriuretic Peptides Represent a “Myocyte
Level” View of Congestion
Help!

9. Maisel AS et al. N Engl J Med. 2002;347:161-167.
1.0
0.8
0.6
0.4
0.2
0.0
0.0 0.2 0.4 0.6 0.8 1.0
1-Specificity
Sensitivity
Final Diagnosis
Heart Failure
Final Diagnosis
NOT Heart Failure
BNP 100 pg/mL
“Test positive”
673 227
BNP <100 pg/mL
“Test negative”
71
Sensitivity
=90%
615
Specificity
=73%
Positive
predictive
value=75%
Negative
predictive
value=90%
BNP=50 pg/mL
BNP=80 pg/mL
BNP=100 pg/mL
BNP=150 pg/mL
BNP=125 pg/mL
Natriuretic Peptides for Diagnosis
Optimal cut-off point determined @ 100 pg/mL
Maisel AS et al. N Engl J Med. 2002;347:161-167.

10. Natriuretic Peptides and Prognosis in Chronic HF:
Data from Val-HeFT
Anand, I. et al, Circ 2003

11. Predischarge BNP Is Strong Predictor of Post-
Discharge Events
0
25
50
75
100
0 30 60 90 120 150 180
DeathorReadmission,%
Follow-up, Days
Hazard Ratios
15.2
5.1
1
p<.0001
p<.0001
BNP >700 ng/L*
(n = 41, events = 38)
BNP 350-700 ng/L*
(n = 50, events = 30)
BNP <350 ng/L*
(n = 111, events = 18)
Logeart D, et al. J Am Coll Cardiol. 2004;43:635-641.

12. Change in NTproBNP and Outcomes
Masson, JACC 2008

13. Kociol R et al, Circ HF 2013

14. Biomarker Guided Therapy and All-Cause Mortality:
Meta-Analysis
Combined
BATTLESCARRED
STARS-BNP
STARBRITE
Troughton
TIME-CHF
PRIMA
Felker GM. Am Heart J 2009
N = 1627
Adjusted HR = 0.69 (0.55-0.86)

15. High Risk Systolic HF Patient
LVEF ≤ 40 within 12 months
HF event within 12 mos (HF hosp, ER visit, or outpt IV diuretic)
NTproBNP > 2000 pg/mL within last 30 days
Usual Care
N= 550
Primary endpoint: Time to CV death or first HF hospitalization
Secondary Endpoints: All-cause mortality
Total days alive and out of hospital during follow-up
CV mortality or CV hospitalization
Safety
Health related quality of life
Resource utilization, costs, cost-effectiveness
Biomarker Guided
NTproBNP < 1000 pg/mL
N=550
Follow up: 2 wks, 6 wks, 3 months, then Q3 month for 12-24 mos
Screening
Randomization
Follow-up
Endpoints
Additional 2 week follow up after changes in therapy

16. Ambulatory/Outpatient
In ambulatory patients with dyspnea, measurement of
BNP or N-terminal pro-B-type natriuretic peptide (NT-
proBNP) is useful to support clinical decision making
regarding the diagnosis of HF, especially in the setting of
clinical uncertainty.
Measurement of BNP or NT-proBNP is useful for
establishing prognosis or disease severity in chronic HF.
I IIa IIb III
I IIa IIb III

17. Hospitalized/Acute
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.
Measurement of BNP or NT-proBNP and/or cardiac
troponin is useful for establishing prognosis or disease
severity in acutely decompensated HF.
I IIa IIb III
I IIa IIb III

18. Advantages of Natriuretic Peptides as
Measures of Congestion
• Quantitative
• Reproducible across time and across providers
• Does not require high level of expertise
• Non-invasive
• Cheap (relatively)
• Supported by guidelines with highest level of
recommendation

19. Biomarkers Always Augment Clinical Judgment
• Impacted by
– Age
– Gender
– Renal function
– Atrial fibrillation
– Obesity
– HFpEF vs. HFrEF

20. Greater Decongestion = Better Outcomes
Kociol et al, Circ HF 2013
• Drop in NT-
proBNP
• Change in
weight
• Net fluid loss

21. Conclusions
• Natriuretic peptides represent a quantitative,
reproducible assessment of myocyte wall stress
– Best marker for making diagnosis of HF
– Correlate with symptoms
– Correlate with outcomes
– Change with favorable change in clinical course
– Failure to improve with treatment identifies very high risk
patients
– ? Potential target for adjusting therapy