Marc A. Silver, MD

1
Update on Clinical Approaches for the Use of
Natriuretic Peptides in Cardiovascular
Disease Outpatient BNP Testing
Marc A. Silver, MD Clinical Professor and
Chairman, Department of Medicine Director, Heart
Failure Institute Advocate Christ Medical
Center Systemwide Physician Leader, Heart
Failure Advocate Healthcare
2
A
B
C
D
Obesity Diabetes Hypertension Abn. Sleep
Diastolic Dysfunction
LVH
Systolic Dysfunction
Heart Failure Syndrome
Death
Hypertension Smoking Lipids Diabetes
MI
LV Remodels
Time Decades
Time Months
3
Stages A-B
Onset Stage C
4
Evidence-Based Approach to Left Ventricular
Dysfunction
Monitor Therapy / Disease Modification
X
X
X
X
Moderate CHF
Severe CHF
Mild CHF
ALVD
Pre- Heart Failure
ALVDasymptomatic left ventricular dysfunction.
5
Evidence-Based Approach to Left Ventricular
Dysfunction
Choose Therapy / Monitor Disease Regression
Moderate CHF
Severe CHF
Mild CHF
ALVD
Pre- Heart Failure
ALVDasymptomatic left ventricular dysfunction.
6
Current and Potential Roles Of BNP Measurement(s)

• Screening of High Risk Patients (Stage A)
• Determination of use of more costly screens
• Early Detection of Disease Progression (Stage
  A-C)
• Monitoring/Guiding Adequacy of Therapy
• In-patients (Need for admission /timing of D/C)
• Out-patients / clinic
• Prognosis
• Determination of escalation / application of
• limited resources (ICDs)
• Risk Stratification for CAD/ SD

7
Framingham Study Asymptomatic LV Dysfunction
(ALVD)
1.0
Stage A
0.8
No ALVD (EF gt50) and noHF history
0.6
Stage B
Survival
0.4
Mild ALVD (EF 40 to 50)
Plt.0001
0.2
Moderate-to-severe ALVD (EF lt40)
Systolic HF (EF ?50)
0.0
0
2
4
6
8
10
12
Years
Wang TJ et al. Circulation. 2003108977-982.
8
233 Community Dwelling Individuals with Risks for
HF
Hyperlipidemia (48) Hypertension (48) Age gt 65
years (45) Tobacco Use (45) CAD DM But NO
HF! 91 had gt 1 Risk
Silver M, et al. Congestive Heart Failure 2003,
9127-132
9
Screening for Heart Failure Role of BNP Levels
On day of screening 48 had systolic
hypertension 59 had diastolic hypertension 82
had 1 symptom that could be attributable to HF
Silver M, et al. Congestive Heart Failure 2003,
9127-132
10
Screening for Heart Failure Role of BNP Levels
BNP Levels Ranged from 0 to 479 pg/ml (mean 40
pg/ml) (Men mean 39 pg/ml Women 42 pg/ml) 24
(10.3) had levels gt 100 pg/ml 32 (13.7) had
levels gt 80 pg/ml No significant difference in
the number of risk Factors and the BNP level
Silver M, et al. Congestive Heart Failure 2003,
9127-132
11
Screening for Heart Failure Role of BNP Levels
Silver M, et al. Congestive Heart Failure 2003,
9127-132
12
NEJM 2004 350655-63
13
Death
NEJM 2004 350655-63
Lowest 1/3 lt 4.0 pg/ml Middle 1/3 4.1 to 12.7
pg/ml Highest 1/3 gt 12.8 pg/ml
HF
14
Conclusions

• In this community-based sample, plasma
  natriuretic peptide levels predicted the risk of
  death and cardiovascular events after adjustment
  for traditional risk factors
• Excess risk was apparent at natriuretic peptide
  levels well below current thresholds used to
  diagnose heart failure

15
BNP Levels in Patients With Dyspnea Secondary to
CHF or COPD
N56 N94
Maisel, A. et al. J. American College of
Cardiology, Vol 37, No. 2, 2001
16
BNP Levels in Patients With Edema Diagnosed With
CHF or Without CHF
N44 N44
Maisel, A. et al. J. American College of
Cardiology, Vol 37, No. 2, 2001
17
Consensus Statement 8 BNP Screening in
Higher-Risk Populations 8.1 At this time, BNP
testing is not appropriate for screening
asymptomatic, low- risk populations for LV
systolic dysfunction. 8.2 There may be some value
in using plasma BNP to screen high-risk subgroups
of the population such as post-MI patients,
diabetic patients, or those with an extended
history of uncontrolled hypertension. It is
important to note that echocardiography is likely
to remain the main method of assessing LV
function in this setting.
18
BNP vs. EF by Echocardiography
Davis et al. Lancet 1994343440-4.
19
Heart Failure Diagnostic Algorithm
Patient with dyspnea or other CHF signs/symptoms
Diagnostic for CHF
History/physical exam/ECG/chest x-ray
Acute/chronic CHF management (echocardiography,
if not done previously)
Nondiagnostic
Positive
BNP blood test
Negative
Evaluate for non-CHF etiologies (echocardiography
usually not indicated)
Adapted from Maisel A. Rev Cardiovasc Med.
20023(suppl 4)S10S17.
20
Discriminate Function of BNP
Maisel, A. et al. J. American College of
Cardiology, Vol 37, No. 2, 2001
21
Causes of Hospital Readmission for Congestive
Heart Failure
Diet Noncompliance 24
Rx Noncompliance 24
16 Inappropriate Rx
17 Other
19 Failure to Seek Care
Vinson J Am Geriatr Soc 1990381290-5
22
BNP Algorithm Wet BNP level versusdry BNP level
Decompensated CHF volume overload BNP 1000
pg/ml (wet)
Inpatient Rx
Rx diuretics vasodilators
Goal
Relief of symptoms euvolemia
BNP levels
? to lt 500 reflecting dry-weight BNP
Uptitrate ACE, B-blockers BNP Monitoring for
Early Detection of Decompensation
Outpatient Rx
Discharge
Goal
Reverse remodeling

• from dry-weight BNP
• 100-200 pg/ml preferable

BNP levels
23
BNP Guided Therapy
Lancet 2000 Heart Failure Reviews, 2003 Eur J
Heart Fail. 2004 Mar 156(3)351-4
24
The hope is that RABBIT / BATTLE SCARED /STAR
will not only demonstrate that BNP levels can
guide therapy, but perhaps can help us monitor
the type of drugs we use and how far to titrate
that drug
25
Another Genie About to Get Out of the Bottle
BNP
26
Intervention was BNP measurement once every 3
months (BNP group) or no BNP measurement
(clinical group). Clinical and utility data were
retrieved from published studies.
Cost-effectiveness was measured by per
quality-adjusted life year (QALY). RESULTS The
baseline analysis during the 9-month period after
hospitalization showed the QALY to be longer for
the BNP group and the costs were also lower for
the BNP group (9577 and 10,131). The dominance
of the BNP group continued during the 1-year
follow-up. CONCLUSIONS Introduction of BNP
measurement in heart failure management may be
cost-effective.
27
Clinical features and medical therapy at
discharge in 521 post-MI patients
Tapanainen JM et al. J Am Coll Cardiol 2004
43757-763.
28
Clinical features and medical therapy at
discharge in 521 post-MI patients
Tapanainen JM et al. J Am Coll Cardiol 2004
43757-763.
29
Clinical features and medical therapy at
discharge in 521 post-MI patients
Multivariate predictors of SCD
30
(No Transcript)
31
B-Type Natriuretic Peptide as a marker for Sudden
Death Risk
Berger Circulation 20021052392-2397
32
B-Type Natriuretic Peptide as a marker for Sudden
Death Risk
(gt 130 pg/ml)
Berger Circulation 20021052392-2397
33
Progressive LV Dilation
34
Signal Transduction 101
Agonist
Receptor
Signal Transduction Cascade
35
Am J Cardiol 200494740-745
36
Am J Cardiol 200494740-745
37
BNP During(On1), Short-term Discontinuation(Off)
and Reinitiation (On2) of CRT
p lt 0.001
p lt 0.001
382
BNP (pg/ml)
282
262
Off
On1
On2
Sinha AM et al, Am J Cardiol. 2003, 1591755-8
38
BNP and Guidelines Documents
  9 Measurement of B-type natriuretic peptide
(BNP) should be considered in the evaluation of
patients presenting in the urgent care setting
where the clinical diagnosis of the cause of
dyspnea is uncertain. (Level of Evidence B)  
  4 Measurement of BNP may be considered in the
outpatient evaluation of patients where the
clinical diagnosis of heart failure is uncertain
or ambiguous. (Level of Evidence C)
  1 The value of serial measurements of BNP to
guide therapy for patients with HF is unknown.
(Level of Evidence C).
39
BNP Providing actionable health information
Treatment/ recurrence monitoring
Predisposition screening
Targeted screening
Treatment stratification
Diagnosis
Prognosis