Nesiritide Natrecor Recombinant human Brain Natriuretic Peptide hBNP

1
(No Transcript)
2
Role of Biomarkersin Heart Failure
Gregg C. Fonarow, MD
Eliot Corday Professor of Cardiovascular Medicine
and Science UCLA Division of Cardiology Director,
Ahmanson-UCLA Cardiomyopathy Center Director,
UCLA Cardiology Fellowship Training
Program Co-Director, UCLA Preventative Cardiology
Program Los Angeles, California
3
Diagnosis of Congestive Heart Failure Clinical
Challenge

• Symptoms and signs of heart failure, like
  shortness of breath and edema, have a broad
  differential diagnosis
• Physical exam is neither sensitive nor specific
  for CHF and, even in good hands, there are often
  errors
• Chest X-ray findings have limited accuracy for
  CHF
• One-third to one-half of patients with CHF have
  normal systolic function

Maisel A et al. J Am Coll Cardiol.
200137(2)379-385.
4
The Limited Reliability of thePhysical
Examination in Heart Failure

• Prospectively compared physical signs with
  hemodynamic measurements in 50 hospitalized
  patients
• Rales, edema, jugular venous pulse elevation
  absent in 18 of 43 patients with pulmonary
  capillary wedge gt24mmHg
• Sensitivity 58, Specificity 100

Stevenson and Perloff. JAMA. 1989261884-888.
5
Methods Used in theDiagnosis of Heart Failure

• Electrocardiogram
• Chest x-ray
• Echocardiogram
• Stress test (echo / nuclear imaging)
• Sprial computed tomography (CT) scanning
• Right heart catheterization (Swan-Ganz)
• Left heart catheterization

6
Chest X-Ray in Heart Failure
7
Clinical Indecisionin the Emergency Room
Physician Report on Clinical Probability of
Congestive Heart Failure
8
Assessment of Severity andProgression of
Congestive Heart Failure

• Symptoms do not correlate well with left
  ventricular dysfunction or with prognosis
• Many markers are elevated in CHF (cytokines,
  catecholamines, etc) but are not useful in
  assessing severity or following progression
• Wide variability in values
• Difficult to measure
• Not often elevated until CHF is severe

9
B-Type Natriuretic Peptide (BNP)

• 32-amino acid peptide secreted primarily from the
  ventricles of the heart
• Released in response to stretch and increased
  volume in the ventricles
• BNP levels correlate with
• Left ventricular end-diastolic pressure and
  volume
• New York Heart Association (NYHA) functional
  classification
• Extent of reversible ischemia
• Rapid, point-of-care assay for BNP now available
  to facilitate diagnosis of CHF and use as a
  prognostic marker

10
Natriuretic PeptidesThe Heart as a Secretory
Organ

• Atrial stretch receptors link blood volume to
  renal function
• Distension of a balloon catheter in atria of dogs
  resulted in diuresis
• Henry et al (1956)
• Secretory granules discovered in the atria
• Kisch (1956)
• Jamieson and Palade (1964)
• BNP was characterized by amino acid sequence and
  DNA clones
• Sudoh et al (1988)
• Seilhamer et al (1989)

Jamieson and Palade. J Cell Biol. 196423151.
11
Natriuretic Peptides
12
Natriuretic PeptidesOrigin and Stimulus of
Release
Peptide Primary Origin Stimulus of
Release ANP Cardiac atria Atrial
distension BNP Ventricular myocardium Ventricular
overload CNP Endothelium Endothelial stress
ANP Atrial Natriuretic Peptide BNP B-type
Natriuretic Peptide CNP C-type Natriuretic
Peptide
Adapted from Burnett JC. J Hypertens.
200017(Suppl 1)S37-S43.
13
BNP Levels in Non-CHF Patients
All non-CHF
Non-CHF Female
Non-CHF Male
100
(n478)
BNP (pg/mL)
50
0
65-74
All
55-64
75
Age
14
BNP Levels in OtherCommon Conditions
Yes
No
60
50
40
BNP (pg/mL)
30
20
10
0
Hypertension
Diabetes
COPD
African American
Caucasian
15
Relationship of BNP and NYHA Classification
1200
977.7
1000
800
Mean
678.6
BNP (pg/mL)
600
396.5
400
167.5
200
0
Class I
Class II
Class III
Class IV
Triage BNP package insert. Data on File at
Biosite Diagnostics Inc.
16
Utility of B-Type Natriuretic Peptide (BNP) in
the Diagnosis of Congestive Heart Failure in an
Urgent-Care Setting

• 250 patients presenting to the ED with shortness
  of breath
• Consent signed
• Data recorded History, physical exam, lab tests
• ED assessment
• BNP values recorded
• 2 cardiologists (blinded to BNP) review all
  records and diagnostic tests including
  echocardiography

Dao Q, Maisel A, et al. J. Am Coll Cardio.
200137(2)379-385.
17
BNP Levels of Patients Diagnosed Without CHF,
With Baseline Left Ventricular Dysfunction, and
With CHF
Plt0.001
1400
1076 138
1200
1000
800
Mean BNP Concentration (pg/mL)
600
400
141 31
200
38 4
0
Asymptomatic LV Dysfunction (n14)
No CHF (n139)
CHF (n97)
Dao Q, Maisel A, et al. J. Am Coll Cardio.
200137(2)379-385.
18
BNP Levels in Patients with Dyspnea Secondary to
CHF or COPD
1200
1076 /- 138
1000
800
BNP (pg/mL)
600
400
200
86 /- 39
0
COPD n56
CHF n94
Cause of Dyspnea
Dao Q, Maisel A, et al. J. Am Coll Cardio.
200137(2)379-385.
19
BNP Concentration for the Degree of CHF Severity
2013 266
2500
2000
1500
BNP Concentration (pg/mL)
791 165
1000
500
186 22
0
Moderate (n34)
Mild (n27)
Severe (n36)
Dao Q, Maisel A, et al. J. Am Coll Cardio.
200137(2)379-385.
20
BNP Levels in Patients With Edema Diagnosed With
CHF or Without CHF
1200
1038 /- 163
1000
800
600
BNP (pg/mL)
400
200
63 /- 16
0
No CHF n44
CHF n44
Cause of Edema
Dao Q, Maisel A, et al. J. Am Coll Cardio.
200137(2)379-385.
21
BNP Assay for DifferentiatingHeart Failure from
Lung Disease
1000
900
800
700
600
BNP (pg/mL)
500
400
300
200
100
0
CHF
COPD
Asthma
ActBronch
Pneumonia
PE
Cause of Dyspnea
321 Patients with dyspnea (gold standard dx of
CHF, pts with COPD with RHF dx with
CHF). Morrison LK et al. J Am Coll Cardiol.
200239202-209.
22
Correction of MisdiagnosedCases Using the BNP
Test
Number of Patients with the Indicated BNP Levels
Number of Patients
Mean BNP Concentration
Diagnoses
gt80 pg/mL
lt80 pg/mL
Overdiagnosed
15
46 13
1
14
Underdiagnosed
15
747 337
15
0
Maisel A et al. J. Am Coll Cardio.
200137(2)379-385.
30 out of 250 patients where the EMC physicians
diagnosis differed from the gold standard
diagnosis.
23
Multivariate Analysis with BNP Analyzed Last
All 250 Cases
Chi- Sens Spec Accuracy Variable Square
Significances () () ()
History of CHF 89.01 0 62 93 80 Heart
size 31.96 0 77 91 85 Murmurs 19.24 0 77 91 85 Pul
m. Venous Hypertension 11.9 0.006 78 91 86 EKG-Atr
ial Fibrillation 9.06 0.0026 80 91 86 Pedal
Edema 9.96 0.0016 89 89 89 BNP 95.23 0 96 96 97
Dao Q, Maisel A, et al. J. Am Coll Cardio.
200137(2)379-385.
24
BNP Combined withClinical Judgment
AUC .86 (.84-.88) ED Probability .90 (.88-.91)
BNP .93 (.92-.94) Combined
25
BNP vs NHANES and Framingham Criteria
Comparative Accuracy
N1586
Plt0.0001
90
83
Accuracy ()
73
70
67
50
NHANES
Framingham
BNP
26
Clarification of Diagnosis and BNP
43
45
40
35
30
25
Indecision ()
20
15
11
10
5
Plt0.0001
0
Clinical Evaluation and BNP
Clinical Evaluation
27
BNP in Left Ventricular Dysfunction
1200
1077/-272
1000
800
567/-113
600
BNP (pg/mL)
391/-89
400
200
30
0
Normal n105
Systolic n53
Diastolic n42
Systolic Diastolic n14
200 patients referred for echocardiography to
evaluate LV dysfunction. Maisel A, De Maria A, et
al. Am Heart J. 2001141(3)367-374.
28
BNP Levels in Impaired vsRestricted vs
Pseudonormal Typesof Diastolic Dysfunction
Impaired n46
Restricted n37
Pseudonormal n15
200 patients referred for echocardiography to
evaluate LV dysfunction. Maisel A, De Maria A, et
al. Am Heart J. 2001141(3)367-374.
29
ROC Curve for BNP Concentration in Predicting
Left Ventricular Dysfunction (Systolic or
Diastolic)
1.0
62
0.9
49
0.8
75
110
0.7
0.6
160
Sensitivity
0.5
0.4
345
AUC 0.952 (0.93-0.97) Plt0.001
0.3
0.2
0.1
0.0
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1-Specificity
30
Changes in Endogenous BNP Levels and Pulmonary
Wedge Pressure During 24 Hours of Diuretic and
Vasodilator Treatment
33
31
PAW
BNP
29
27
25
BNP (pg/mL)
PCW (mm Hg)
23
21
19
17
15
baseline
4
8
12
16
20
24
Hours
15 heart failure patients responding to
vasodilators and diuretics Maisel. Cardiovascular
Symposium Highlights 2001.
31
Relationship Between BNP Concentrationand
Pulmonary Artery Wedge Pressure
Change per hour
BNP
PAW (mm Hg)
R0.729 Plt0.05
0
1
2
3
4
5
6
7
PAW
BNP (pg/mL)
Maisel A, Kazenegra R, et al. J Cardiac Failure.
20017(1)21-29.
32
Symptoms, Left Ventricular Dysfunction,and
Prognosis in Heart Failure
33
Predictors of Mortality inPatients with Heart
Failure

• Age
• Sex
• Socio-economic status
• Race/ethnicity
• Coronary artery disease (CAD)
• Diabetes
• NHYA Class
• Systolic blood pressure (SBP)
• Mean arterial pressure (MAP)
• Heart rate (HR)
• QRS duration
• QT dispersion
• NSVT
• PVC frequency
• Atrial fibrillation
• Syncopy
• Pulmonary capillary wedge (PCW)

• Degree of mitral regurgitation (MR)
• Degree of TR
• Peak Oxygen Consumption
• 6-minute walk
• Heart rate recovery
• Serum sodium
• Blood urea nitrogen (BUN)
• Creatinine
• Uric acid
• Hemoglobin
• Norepinephrine
• Renin
• Angiotensin II
• Aldosterone
• Anti-diuretic hormone (ADH)
• B-natriuretic peptide (BNP)

34
A Clinical Index to Predict Survival in
Ambulatory Advanced HF Patients

• Noninvasive model
• Ischemic cardiomyopathy 0.693 12.00 (1.35,
  2.97) 11.71 .0006
• Resting heart rate (bpm) 0.021 61.02 (1.01,
  1.04) 11.45 .0007
• LVEF () -0.046 40.96 (0.93, 0.98) 10.65 .0011
• Mean blood pressure -0.0255 0.98 (0.96,
  0.99) 8.94 .0028
• IVCD 0.608 31.84 (1.22, 2.76) 8.55 .0035
• Peak VO2 -0.0546 0.95 (0.91, 0.99) 6.76 .0093
• Serum sodium -0.0470 0.95 (0.92, 1.00) 4.76 .0292

Aaronson KD. Circulation. 199795(2)2660-2667.
35
BNP Concentration for the Prediction of Clinical
Events
45
40
35
30
BNP gt480 pg/mL
25
Death or CHF Hospitalization ()
20
15
BNP 230-480 pg/mL
10
5
BNP lt230 pg/mL
0
0
20
40
60
80
100
120
140
160
180
Time (d)
Harrison A et al. Ann Emerg Med.
200239(2)131138.
36
Cumulative Survival Rates in CHF Patients with LV
Dysfunction Stratified on Median Plasma BNP
Concentration
100
BNP lt73 pg/mL
80
Plt0.0001
60
Cumulative Survival ()
40
BNP gt73 pg/mL
20
0
0
10
20
30
40
50
Months
Tsutamoto T et al. Circulation. 199796509-516.
37
BNP Levels Predict Heart Failure Mortality
Independent of Other Markers
Heart Failure Mortality Rates
DiagnosticTest
Low
High
P value
RR
BNP
1/145 (0.7)
23/151 (15.2)
Plt0.0000001
22.1
LVEF
7/150 (4.7)
17/129 (13.2)
Plt0.028
2.2
297 patients with LV dysfunction/CHF in the ANZ
trial. Median BNP 99 pmol/L, LVEF 0.29. Richards
AM et al. J Am Coll Cardio. 2001371781-1787.
38
BNP Levels Independently Predict Mortalityin
Patients Referred for Echocardiography
20
OR 2.5 Plt0.00001
17.0
15
10
Mortality ()
6.8
5
0
BNP Low
BNP High
4-Year Mortality Predictors age, BNP, CAD, male
1640 patients referred for echocardiography,
followed for 4-year mortality rates. Dargie HJ.
Heart. 20018621-26.
39
Baseline BNP and Mortality in HFVal-HeFT Study
RR 95 CI
1.0
Q1 lt41
1.0
0.9
0.8
Q2 41-97
1.47 (1.15-1.89)
Survival
0.7
Q3 97-238
2.27 (1.80-2.86)
0.6
Q4 gt238
3.95 3.18-4.92)
0.5
Plt0.0001
0
0
24
12
36
48
Month
Anand IS et al. Circulation. 20031071276-1281.
40
Change in BNP and Mortality in HFVal-HeFT Study
25
19.1
20
15.5
15.1
15
13.6
Mortality ()
10
5
0
Change from baseline to 4 months
Quartile change BNP gt -45 -45 to -13 -12 to
30 gt 30 Mean change BN -143 - 57 8 188 Mean
chang -66 -30 6 380
Anand IS et al. Circulation. 20031071276-1281.
41
BNP Levels Independently Predict Mortality in
Patients with ESRD on Hemodialysis
8
7.14
7
6
Mortality OR 7.14 (95 CI 2.83-18.0) Plt0.00001
5
Mortality OR
4
3.20
3
2
1.00
1
0
BNP tertile 1
BNP tertile 2
BNP tertile 3
246 patients on hemodialysis without clinical CHF
diagnosis J Am Soc Nephr. 2001121508-1515.
42
BNP Predicts Sudden Death in Patients with
Chronic Heart Failure
452 pts with HF, LVEF lt35, BNP gt13 0 pg/mL only
multivariate predictor of SD (P0.0006)Berger.
Circulation. 20021052392-2397.
43
Improved Survival with Prophylactic ICD Therapy
Patients with Prior MI and LVEF 30 MADIT-II
Mortality 19.8 vs 14.2 HR 0.69
(0.51-0.93) P0.016 NNT 18
P0.007
1232 Patients Stage B or Class II-III HF, Prior
MI, LVEF 0.30, on top of optimal medical
therapy, f/u 20 months. Moss AJ. N Engl J Med.
2002346877-883.
44
Troponins for Risk Stratification in HF

• There is increasing evidence that myocyte
  necrosis and apoptosis contribute to progressive
  left ventricular dysfunction in heart failure
• Olivetti. N Engl J Med. 1997 3361131-1141.
• Anversa. Circulation Res. 1998141247-253.
• Several studies have reported elevation of
  cardiac troponin in patients with decompensated
  heart failure, in the absence of ACS or CAD
• Sato. Circulation. 2001103369-374.
• La Vecchia. J Heart Lung Transplant.
  200019644-652.
• Setsuta. Am J Cardiol. 199984608-611.
• Several studies and have correlated troponin
  elevation with poor prognosis in heart failure
• Sato. Circulation. 2001103369-374.
• La Vecchia. J Heart Lung Transplant.
  200019644-652.
• Setsuta. Am J Cardiol. 199984608-611.

45
Troponins and Risk of Mortality in Heart Failure
100
Plt0.01
90
75
80
70
60
CV Event Risk ()
50
40
30
20
15
10
0
cTnT lt0.02 ng/mL
cTnT gt0.02 ng/mL
60 patients DCM and HF. Sato. Circulation.
2001103369.
46
UCLA Multi-Marker Strategy(Troponin I and BNP)
in HF Study

• Analyzed 251 HF patients referred to UCLA
  Cardiomyopathy Center between 6/00 and 3/02
• Patients with acute MI or myocarditis excluded
  (n13)
• Troponin I Assay drawn at time of initial
  presentation -level of detection 0.04 ng/mL
• Stratus CS STAT fluorometric analyzer, Dade
  Behring, Deerfield, IL.
• BNP (B-type natriuretic peptide) Assay drawn at
  time of initial presentation
• Fuorescence immunoassay kit, Triage, Biosite
  Inc., San Diego, CA
• Survival was measured from the date of initial
  evaluation.Primary endpoint was mortality or
  need for urgent transplantation

Horwich TB, Fonarow GC. Circulation.
2002106II-647.
47
Relationship Between Troponin I and Mortality in
Patients with Advanced HF
100
TnI lt0.04
80
60
Survival ()
TnI ?0.04
40
RR 2.1, 95 CI 1.3-3.5 Plt0.0001
20
0
0
2
4
6
8
10
12
14
16
18
Months
Horwich TB, Fonarow GC. Circulation.
2002106II-647.
48
Relationship Between BNP andMortality in
Patients with Advanced HF
100
BNP lt485 pg/mL
90
80
70
60
50
BNP 485 pg/mL
40
RR 3.7, 95 CI 2.0-6.9 Plt0.0001
30
20
10
0
0
2
4
6
8
10
12
14
16
18
20
22
24
Months
BNP cut point by ROC
Horwich TB, Fonarow GC. Circulation.
2002106II-647.
49
Addition of BNP to TnIImproves Prognostic Value
BNP-TnI-
BNP- TnI
BNP TnI-
BNPTnI
n34
n17
n22
n23
TnI -, TnI lt0.04 ng/mL TnI, TnI 0.04
ng/mL BNP-, BNP lt485 pg/mL BNP, BNP 485 pg/mL
Horwich TB, Fonarow GC. Circulation.
2003108833-838.
50
Multi-Marker Strategy for Risk Stratification and
Heart Transplant Selection
RR
1.0
TnI - BNP -
TnI BNP -
1.0
0.9
TnI - BNP
2.1
0.8
Survival
S/P Heart Transplant
4.7
0.7
0.6
TnI BNP
12.3
0.5
0
0
12
6
18
24
Month
Horwich TB, Fonarow GC. Circulation.
2002106II-647.
51
Multi-Marker Strategy for Assessmentof Heart
Failure

• BNP is a significant independent predicator of
  mortality in heart failure. Changes in BNP over
  time are associated with morbidity and mortality
• Cardiac troponins are also a significant
  independent predictor of mortality in heart
  failure
• Patients with detectable TnI and elevated BNP are
  at particularly high risk for adverse outcomes
• This multi-marker strategy provides a simple,
  clinically useful means to risk stratify patients
  with Heart Failure

52
BNP Elevations

• Right sided heart failure
• Cor pulmonale 200-500 pg/mL
• Primary pulmonary hypertension 200-500 pg/mL
• Acute pulmonary embolism 150-500 pg/mL
• Non heart failure elevations
• Acute coronary syndromes 40 - 400 pg/mL
• Acute myocardial infarction 40 - gt1300 pg/mL
• End-stage renal disease 80 - gt1300 pg/mL

53
BNP to Risk Stratify Patients withAcute Coronary
Syndromes
BNP 80 pg/mL (n1251)
10
BNP gt80 pg/mL (n1274)
8
6
Percent of Patients ()
4
2
0
Death
CHF
MI
Death
CHF
MI
30 days
10 months
Plt0.005 for each comparison
Braunwald. N Engl J Med. 2001. Vol 345, No. 14.
54
BNP to Risk Stratify Patients withAcute Coronary
Syndromes
Q1
Q2
Q3
Q4
BNP Level (pg/mL) 5-44 44-81
82-138 139-1456
16
12
10-month Mortality ()
P0.02 Plt0.001 Plt0.001
8
4
0
ST Elevation Non-ST Elevation
Unstable Angina Myocardial Infarction
Myocardial Infarction
n 825
565
1133
2525 patients with ACS in TIMI-16 (orofiban vs
placebo) BNP level at average 40
hours. Braunwald. N Engl J Med. 2001345(14).
55
Troponin I (TnI), C-Reactive Protein (CRP), and
B-type Natriuretic Peptide (BNP) as Determinants
of 30-Day Mortality in Acute Coronary Ischemia
A Multimarker Approach
OPUS-TIMI 16
TACTICS-TIMI 18
6
13
6
14
P.014
Plt.0001
12
5
10
3.5
4
8
30-Day Mortality Risk ()
3
5.7
6
1.8
2
4
1
2.1
1
1
2
n90
n78
n324
n67
n150
n155
n717
67
150
155
78
504
717
324
90
n504
0
0
0
1
2
3
0
1
2
3
No. of Elevated Biomarkers
No. of Elevated Biomarkers
Sabatine MS, et al. Circulation.
20021051760-1763.
56
Heart Failure Diagnostic Algorithm
Patient presenting with dyspnea
Physical examination, chest x-ray, ECG, BNP level
BNP lt100 pg/mL
BNP 100-400 pg/mL
BNP gt 400 pg/mL
CHF very unlikely (2)
CHF very likely (95)
Baseline LV dysfunction, underlying cor pulmonale
or acute pulmonary embolism?
Yes
No
Possible exacerbation of CHF (25)
CHF likely (75)
Maisel A. Rev Cardiovasc Med. 20023(suppl 4)S13.
57
Brain Natriuretic Peptide for AcuteShortness of
Breath Evaluation (BASEL)
Patients with Acute Dyspnea
Randomized
BNP group n225
Clinical group n227
Time to discharge
History, Physical Exam, ECG, Chest X-ray, Blood
Tests, SaO2
Rapid BNP Test (15min)
Start of Specific Treatment
Hospital Discharge
30 Day Outcomes
N Engl J Med. 2004350647-654.
58
Brain Natriuretic Peptide for AcuteShortness of
Breath Evaluation (BASEL)
N Engl J Med. 2004350647-654.
59
Brain Natriuretic Peptide for AcuteShortness of
Breath Evaluation (BASEL)
N Engl J Med. 2004350647-654.
60
Brain Natriuretic Peptide for AcuteShortness of
Breath Evaluation (BASEL)
8000
14,0

7000
12,0
-23
-26
6000
-26
10,0

5000
Total Treatment Cost ()
8,0
Time to Discharge (days)
4000
P0.009
6,0
3000
P0.006
4,0
2000
1000
2,0
7264
5410
13.7
10.6
0
0,0
BNP group
Clinical group
BNP group
Clinical group
n225
n227
n225
n227
N Engl J Med. 2004350647-654.
61
BNP versus NT-BNP Assay for HF
McCullough. Rev Cardiovasc Med. 2003.
62
Potential Uses for BNP toDiagnose LV Dysfunction

• Cardiotoxic drugs
• Adriamycin
• Herceptin
• Valve disease
• Aortic
• Mitral
• Diabetes
• Transplant rejection
• Sepsis
• Rule out ARDS without a swan
• Screening for HCM

63
BNP Levels to Monitor Therapy Potential Next
Step

• Hospitalized patients
• BNP levels drops rapidly with treatment (35
  pg/hr) and correlate to falling wedge pressures
• Discharge BNP levelslt400 pg/mL is associated
  with fewer readmissions
• Failure to decrease BNP may portend a
  particularly bad prognosis

• Outpatient management
• BNP levels may reflect titration of therapy
  (vasodilators, diuretics, beta blockers)
• BNP levels lt100 pg/mL are NYHA class I patients
  with good a prognosis despite low LVEF
• BNP levels gt1000 pg/mL are usually associated
  with a class IV patient with an especially bad
  prognosis

64
Treatment of Heart Failure Guided by BNP Levels
Clinical
BNP
Clinical Events
P value
(n38)
(n33)
7
1
0.06
Death
CV Admission
21
0.38
7
Worsened Symptoms
26
11
0.03
Total Events
54
19
0.02
69 patients with heart failure, randomized to
clinical alone or clinical plus BNP-guided
care. Troughton. Lancet. 20003551126-1130.
65
BNP Levels Predict Heart Failure Patients
Deriving Greatest Beta-Blocker Benefit
40
36
35
OR 0.42 Plt0.0001
30
25
Mortality ()
20
15
15
PNS
10
5
4
5
0
Placebo
Carvedilol
Placebo
Carvedilol
BNP Below Mean
BNP Above Mean
297 patients with LV dysfunction/CHF in the ANZ
trial carvedilol vs placebo. Richards.
2001371781-1787.
66
Treatments Associated with a Reduction in BNP
Levels

• Intravenous vasodilators and diuretics
• ACE inhibitors
• Beta blockers
• Spironolactone
• CABG (with improved LVEF)
• LV assist devices
• Heart transplantation (no rejection)

67
Role of the BNP Assay

• Diagnosis BNP levels accurately reflect the
  cause of dyspnea in patients presenting to the ED
  and add additional information beyond standard
  Hx, PE, and diagnostic testing
• Screening BNP accurately detects abnormal left
  ventricular function in patients with or without
  Sx of CHF or a previous history of CHF
• Risk Stratification BNP levels are associated
  with risk of hospitalization and death in
  patients with heart failure and risk of CV events
  and death in patients with AMI and ACS
• Treatment Guide Early studies suggest BNP may
  guide initiation and titration of heart failure
  therapy

68
Clinical Role of Biomarkers

• Phase 1. Facilitation of diagnosis
• Phase 2a. Appreciation of the prognostic value of
  the biomarker
• Phase 2b. Appreciation of the prognostic value of
  a multi-maker strategy
• Phase 3. Integrative interpretation with other
  known clinical factors and use to impact
  treatment strategies

Bozkurt B. Circulation. 20031071231-1233.