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Early Detection and Assessment
of Heart Failure (HF): The Role ofB-Type Natriuretic Peptide (BNP)
23321UMK040105D (04/05
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Review Objectives
Introduce BNP and its role in HF
Review peer-reviewed data on BNP as a diagnostic tool
Present relevant case studies
Discuss the utility of rapid BNP testing in the physician
office setting
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Patient Case Study - 1
Patient:
79 y/o male
WW2 veteran Previously active, now unable
to mow the lawn
Complaining of mild dyspneaand fatigue
History: Hypertensive:
BP147/85, HR 96
No known heart diseaseThe patient cases are unique clinical presentations. Every patient should beevaluated based on the best clinical judgment of the treating physician.Photo not actual patient.
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Patient Case Study - 1
Physical Examination:
Oxygen saturation 94%, respiratory rate of 18
Basilar crackles on lung exam
Trace ankle edema bilaterally
The patient cases are unique clinical presentations. Every patientshould be evaluated based on the best clinical judgment of the treatingphysician. Photo not actual patient.
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Patient Case Study - 1
Disposition:
BNP: 800 pg/mL
Patient referred to ED for admission and further workup
Final diagnosis: Heart Failure
The patient cases are unique clinical presentations. Every patientshould be evaluated based on the best clinical judgment of the treatingphysician. Photo not actual patient.
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The Prevalence of Heart Failure
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Heart Failure Prevalence on the Rise
5 million Americans diagnosed with HF
550,000 new cases per year1
Fourth leading cause of adult hospitalization in U.S.
4.3 million outpatient visits in 20012
60 million individuals at high risk for developing heart
failure
1. American Heart Association, 2002 Heart and Stroke Statistical Update.2. Coronary Heart Disease Statistics: Heart Failure Supplement. 2002 EditiPublication Year: 2004.
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Source: Hunt SA et al. J Am Coll Cardiol. 2001;38:210121
ACC/AHA Practice Guidelines:
Approaches to HF Stages
A
B
C
High Risk for Developing HFHypertension
CAD
Diabetes mellitusFamily history of cardiomyopathy
Asymptomatic HFLV systolic dysfunction
Previous MIAsymptomatic valvular disease
Symptomatic HFKnown structural heart diseaseShortness of breath and fatigue
Reduced exercise tolerance
RefractoryEnd-Stage HF
Marked symptoms at restdespite maximalmedical therapyD
60 Million
10 Million
6 Million
600,000
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Common Risk Factors Associated
with Development of CHF
Hypertension
Coronary Artery Disease Diabetes
Hyperlipidemia
Family history of cardiomyopathy
Only early detection and treatment is likely to stem thecurrent epidemic of heart failure (HF).
Source: Silver M. Congestive Heart Failure, 2003; 1
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Pre-Pro-BNP1-134
26-aa sig
sequen
N-terminal
Pro-BNP1-76
BNP77-108
Pro-BNP1-108
t1/2= 18 min
WALLSTRESS
Natriuresis Vasodilatation RAAS
Release of BNP
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Renin-
Angiotensin-
Aldosterone
BNP
ANP
Vasoconstriction
Sodium retentionPotassium wasting
Natriuresis
Inhibition of RAAVasodepression
Its All About Balance
Renin-
Angiotensin-Aldosterone
BNPANP
VasoconstrictionSodium retentionPotassium wasting
NatriuresisInhibition of RAAVasodepression
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Heart Failure Pathophysiology
Myocardial injury Fall in LV performance
Activation of RAS, NPS, SNS, ET,
AVP and others
Myocardial toxicityPeripheral vasoconstrictio
Hemodynamic alteration
Remodeling and
progressive
worsening of
LV function Heart failure symptomsMorbidity and mortality
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The Cardiovascular Disease Continuum:
Clinical Implications
Source: Adapted from Dzau V et al. Am Heart J. 1991; 121:1244-126
Risk Factors:
Obesity,Insulin Resistance
EndothelialDysfunction
Vascular Disease(Atherosclerosis)
Pathological
Remodeling(LVH)
Heart Attack
(MyocardialDysfunction)
Left VentricularEnlargement
Heart Failure
Death
EndothelialDysfunction
MaladaptivRemodelin
BNP
BNP
BNP
BNP BNP
BNP
BNP
BNP = 0
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Careful physical exam was performed on heart failure patients about toundergo a right heart catheterization
52 patients, mostly New York Heart Association (NYHA) III, average ejectionfraction (EF) 18%
If rales were present, all had a wedge pressure >18, very specific (100%)
However only 9 of 37 with a wedge pressure >18 had rales, very insensitive(sensitivity < 25%)
Soclear lung fields tell you very little about the fluid status in heart failure
Source: Butman et al. J Amer Coll Cardiol. 10/9
HF Diagnostic Dilemma:Cardiovascular Examination in Patients with Severe Congestive Heart Failure (CH
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Specificity and Sensitivity in Diagnosing CHF
100%98%BNP (cutoff value of 100 pg/mL)
57%81%Crackles in the Lungs
26%90%Third Heart Sound
34%92%Elevated Neck Veins
SensitivitySpecificity
100 patients presenting to the ER with signs or symptomsof congestive heart failure (e.g., dyspnea, edema, weight
gain)
Dao and colleagues, 49th Annual Scientific Session the American College of Cardiology
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Source: Adapted from Knudsen C. et al,
Am J Med. 2004;116(6):363-368.
Variable Odds Ratio
History of myocardial infarction 2.5
History of chronic heart failure 4.3
Rales 1.6
Lower extremity edema 2.3
Cardiomegaly 2.3
Cephalization 6.4
Interstitial edema 7.0
Abnormal electrocardiogram 1.9
B-type natriuretic peptide level 100 pg/ml 12.3
Relative Diagnostic Contribution:
Traditional Diagnostic Tools & BNP
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B-Type Natriuretic Peptide (BNP)
Current diagnostic tests are highly sensitive and
specific
Can be used reliably regardless of age, race, gender
or HF etiology
Provides unique clinical information that iscomplementary to other methods used for diagnosis
and assessment of HF
Is available as a test that can be performed in thephysician office laboratory
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BNP Has Revolutionized the
Diagnosis and Assessment of HF
0
500
1,000
1,500
2,000
2,500
3,000
3,500
Mar'01
May'01
Jul'01
Sep'01
Nov'01
Jan'02
Mar'02
May'02
Jul'02
Sep'02
Nov-02
3-Jan
3-Mar
3-May
3-Jul
3-Sep
3-Nov
4-Jan
4-Mar
4-May
4-Jul
4-Sep
4-Nov
Since 2001, over 2,800 U.S. hospitalshave adopted the Triage BNP Test
Peer-reviewed literature exists describing the use of BNP in
prognosis, ischemia, valvular disease and treatment monitoring
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Primary Care Physicians Can Have the Greatest
Impact on Appropriate Heart Failure Care
10%
73%
17%
Primary Care
Physicians
Cardiologists
Other
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BNP Utility Has Evolved
to the Outpatient Setting
Source: Harrison A, Maisel AS et al,Clinical Chemistry 2004; Vol. 50, No. 9: 1714-17
ICU
11%
ER
72%
OP
8%Ward
9%
N = 537
Year 2001N = 1466
Year 2002N = 2072
Year 2003
ICU
18%
ER
20%
OP
47%
Ward
15%Ward
20%
OP
37%
ER
27%
ICU
16%
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Source: Maisel, A. et al. J. American College of Cardiolo
Vol. 37, No. 2, 2001.
HF Diagnosis Study: Methods
250 patients presenting to the ED with shortness of breath
Data recorded: history, physical exam, lab tests
ED assessment
BNP values recorded
Later assessment: confirmation of the diagnosis
2 cardiologists with access to any later tests (echos), hospital
course, response to Rx, etc.
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BNP Levels in Patients with Dyspnea
Secondary to CHF or COPD
86 +/- 39
1076 +/- 138
0
200
400
600
800
1000
1200
BNPp
g/ml
COPD CHF
Cause of Dyspnea
Source: Maisel, A. et al. J. American College of Cardiolo
Vol. 37, No. 2, 2001.
N=56 N=94
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BNP Levels Associated with Baseline Left Ventricular
Dysfunction and with CHF
Source: Maisel, A. et al. J. American College of Cardiolog
Vol. 37, No. 2, 2001.
38+/-4141+/-31
1076+/-138
0
200
400
600
800
1000
1200
BNP
pg/ml
No CHF LV Dysfunction
No acute CHF
CHF
N=139 N=14 N=97
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Correction of Misdiagnosed Cases
Using BNP with a Cut-off of 80 pg/ml
Diagnoses
Number of
Patients
Mean BNP
Concentration >80 pg/ml
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Study Conclusions
BNP levels accurately reflect the cause of dyspnea in patients
presenting to the emergency department
BNP levels add additional information to that gathered by the
physician, allowing the correct diagnosis of congestive heart
failure
Source: Maisel, A. et al. J. AmericanCollege of CardiolVol. 37, No. 2, 2001.
L d k NEJM B thi N t P l (B N P ) St d
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Study Objective:To validate the use of a cardiovascular biomarker,BNP, as an aid in the diagnosis of CHF
Landmark NEJM Breathing Not Properly (B.N.P.) StudRapid Measurement of B-Type Natriuretic Peptide in the Emergency Diagnosis of Heart Fail
Maisel, A., et al.The New England Journal of Medicine,
Vol. 347: 161-167, 2002
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Study Design: B.N.P. Multinational Study
Study Methods:
7 clinical sites from three countries
Prospective study of 1586 patients who presented with
dyspnea
BNP measurement obtained during the initial EDevaluation
BNP results were blinded to physicians
Physicians were asked to assign a value of 0 to 100%for clinical certainty of HF
Source: Maisel, A et al. The New England Journal of Medicin
Vol. 347, 161-167, 2002.
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Frequency Bar Graph
0
50
100
150
200
250
300
350
0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0
Clinical Probability of Heart Failure (blinded to BNP results)
Pretest Probability of Heart Failure
Significant Indecision Exists
Source: (B.N.P. Sub-study) McCullough,P et al. Circulation, July 20
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BNP Adds to Clinical Judgement
81.6
74.0
81.1
70 71 72 73 74 75 76 77 78 79 80 81 82 83
Combined
BNP Level
ClinicalJudgment
Accuracy (%)
P< 0.0001 for BNP vs. Clinical Judgment
or Combined vs. Clinical Judgment
N = 1538 with ED probability of CHF recorded
Source: (B.N.P. Sub-study)
McCullough,P et al. Circulation, July 2002
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Conclusions
Study Conclusions:
BNP measurements improve the ability of clinicians todifferentiate patients with dyspnea due to CHF from those
with dyspnea from other causes
Mean BNP values are related to functional class in thosewith heart failure
BNP has a high degree of sensitivity, specificity and
accuracy for the diagnosis of heart failure
Source: Maisel, A et al.
The New England Journal of Medicine, Vol. 347, 161-167, 200
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Utility of BNP in
Outpatient HF Management
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Targets in Assessing Disease Severity
Many conditions include a target to assess disease severity:
Hypertension Blood Pressure
Diabetes Blood Sugar Level, HbA1
Hypercholesterolemia Cholesterol
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Patient Case Study - 2
Patient:
64 y/o male
Presents to the HF clinic for routinemonthly visit
He is complaining of mild fatigue
History:
Current medicine: Lisinopril andmetoprolol-XL
History of heart failure
The patient cases are unique clinical presentations. Every patient should be evaluabased on the best clinical judgment of the treating physician. Photo not actual patien
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Patient Case Study - 2
Physical Examination
VS: Temp 98.6, O2 Sat 98%, BP 138/95
Neck: No jugular vein distension
Ext: Warm & dry
CV: Regular heart rate and rhythmBaseline BNP: 357 pg/mL
The patient cases are unique clinical presentations. Every patientshould be evaluated based on the best clinical judgment of thetreating physician. Photo not actual patient.
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Patient Case Study - 2
Disposition:
BNP test ordered to assess patient in conjunction with physical exam.
BNP level was 1015 pg/mL
Dose of ACE-I increased and Lasix added
One week later BNP 417
Potential hospital admission averted
The patient cases are unique clinical presentations. Every patientshould be evaluated based on the best clinical judgment of thetreating physician. Photo not actual patient.
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BNP Response to Treatment
(N = 1979) (N = 1940)Placebo Valsartan
20
30
10
0
-10
-20
-30
P< .0001
BNP(pg/mL)
Source: Latini, R., Masson S., et a
Circulation, Vol. 106, No. 19, 2002
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Utility of BNP in
the Physician Office
Algorithm for Use of BNP Testing in a Primary Care
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Source: Maisel A, Koon J, Krishnaswamy P, Kazanegra R, et al. Utility of B-natriuretic peptide as a rapid, point-of-care testfor screening patients undergoing echocardiography to determine left ventricular dysfunction, American Heart Journal 2001; 141
Algorithm for Use of BNP Testing in a Primary Care
Setting in Patients with No Known History of CHF
Patients present with signs
and/or symptoms of CHF.
These include: shortness of
breath, edema, fatigue, JVD,
dyspnea on exertion,
paroxysmal nocturnal dyspnea,
unexplained weight gain,
auscultatory rales or
crackles.
Patients with hypertension,
CAD, previous MI, obesity,
and/or diabetes are at
increased risk for development
of HF. These risk factors
should heighten suspicion for
possible CHF.
Obtain Patient History
Perform Physical Examination Perform EKG Order BNP test Order Chest X-Ray
Order other laboratory tests
Interpret BNP
If BNP 40 and
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Caveats to BNP Interpretation
Obesity
Levels noted to be slightly decreased1
Renal function
Levels slightly elevated but still useful as a diagnostic test2
Pulmonary embolism/Pulmonary HTN
Grey zone BNPs3
Diastolic Dysfunction
Usually less elevation than seen in systolic4
1. Mehra et al. JACC5/2004 and Wang et al, Circulation 2/2. McCullough Am J Kidney Dis2003.3. Leuchte BNP in PPH JACC2004, Kucher Circ 2003.4. Maisel JACC2003.
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Patient Case Study - 3
Patient:
52 y/o female
Dyspnea on exertion over thelast few days
Orthopnea and nonproductive
cough
History:
Hypertension
Tobacco Use
The patient cases are unique clinical presentations. Every patient should beevaluated based on the best clinical judgment of the treating physician. Photonot actual patient.
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Patient Case Study - 3
Physical Examination:
RR 18, O2 sat 95% on room air
2+ pedal edema
BMI 36
Distant but symmetric breath sounds
EKG nonspecific t wave inversions
Creatinine 1.0, blood glucose 231, troponin .04Chest X-Ray see next slide
The patient cases are unique clinical presentations. Every patieshould be evaluated based on the best clinical judgment of thetreating physician. Photo not actual patient.
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Patient Case Study 3 (Chest X-Ray)
The patient cases are unique clinical presentations. Every patiebe evaluated based on the best clinical judgment of the treatingphysician. Photo not actual patient.
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Patient Case Study - 3
Disposition:
Pulmonary function testing reveals marked outflow
obstruction
BNP: 18 pg/mL
Patient did well with bronchodilation therapy Lower extremity edema was simply lymphedema
The patient cases are unique clinical presentations. Every patient sbe evaluated based on the best clinical judgment of the treatingphysician. Photo not actual patient.
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Advances in Rapid Diagnostic Testing
i
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The Triage BNP Test
Triage Platform also provides:
Cardiac markers
Troponin I
Myoglobin
CK-MB
D-dimer TOX Drug Screening
In development:
High sensitivity C-Reactive Protein
Stroke Panel
Contact Biosite Customer Service
for a distributor in your area.
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Assay Procedure
Step 1
Add whole blood to device
Step 2
Insert device into Triage Meter
Step 3
Read Results
Th T i BNP T
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The Triage BNP Test
A Rapid BNP Test
Results in approximately 15 minutes
Whole Blood Testing
Quantitative Measurements
Built-in Quality Control
Potentially relevant CPT Code 83880*
*CPT is a copyright and trademark of the AMA. Please consult the current CPT manuafull descriptors and instructions regarding the use of these codes.