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Title: Scottish Heart Failure Nurse Forum


1
Scottish Heart Failure Nurse Forum
  • June 9, 2006

2
B-Type Natriuretic Peptide Physiology,
Pathophysiology and the Clinical Role
  • Nancy L. Seymour RN, BSN, CCRN
  • International Clinical Consultant Manager
  • Biosite, Inc. International

3
Program Objectives
  • Current challenges associated with HF and ACS
    throughout the healthcare continuum
  • The physiology and pathophysiology of HF and
    cardiovascular diseases.
  • Clinical utility of BNP for diagnosis, assessment
    of disease severity and risk stratification for
    ACS in heart failure.
  • Importance of utilizing BNP to enhance
    recognition of high-risk patients.
  • Current research addressing the utility of HF
    testing at Point-of-Care Testing. 

4
Challenges in Healthcare
  • Highest Quality of Care
  • Patient Satisfaction
  • Minimizing Overcrowding
  • Enhancing Operational Efficiency
  • Optimizing Revenues
  • Managing Costs

5
Heart Failure Pathophysiology
Myocardial injury
Fall in LV performance
Activation of RAAS, NPS, SNS, AVP, Aldosterone,
Cytokines, Endothelin Prostaglandin
Peripheral vasoconstriction Hemodynamic
alterations
Myocardial toxicity
Remodeling and progressive worsening of LV
function
Heart failure symptoms
Morbidity and mortality
6
Congestive Heart Failure
Evolution of Clinical Stages
Class I
Class II
Class III
Class IV
7
ACC/AHA HF Classification Guidelines
  • Stage A
  • Patients at high risk for developing HF but no
    structural disorder of the heart
  • Stage B
  • Patients with structural disorder of the heart
    but who have never developed symptoms of HF
  • Stage C
  • Patients with past or current symptoms of HF
    associated with underlying structural disease
  • Stage D
  • Patients with end-stage disease who require
    specialized treatment strategies

ACC/AHA Guidelines, J American College of
Cardiology, Vol. 36, No. 7, 2001
8
Economic Burden Clinical Challenges
THE HEART FAILURE DILEMMA
  • U.S. prevalence of 5 million, worldwide 15
    million2 of population
  • 5-year survival Males 59
  • 5-year survival Females 45

9
Heart Failure Perspective
  • Risk for Heart Failure
  • Lifetime risk one in five for those gt 40 years
  • Coronary Artery Disease major attributable factor
  • Without history of AMI, risk is one in nine for
    males and one in six for females
  • 75 with antecedent HTN
  • When BP gt160/100 risk is one in four
  • With BP lt 140/90 risk is one in eight
  • Total estimated costs
  • Estimate that total costs for heart disease in
    2004 will be 238.6 billion
  • Heart failure will equal 25.8 billion
  • Hospital charges will equal 13.6 billion
  • American Heart Association Heart Disease and
    Stroke Statistics, 2004 Update
  • Lloyd-Jones et al. Circulation, 2002 103068-71

10
Etiology of Cardiac Dysfunction
  • Systolic Dysfunction
  • Diminished inotropy
  • Ejection Fraction lt40
  • Males 50-70
  • Impaired contractility
  • Chamber dilated
  • Eccentric hypertrophy
  • Cardiomegaly noted
  • Ischemic in nature
  • Audible S3
  • Levy, R Michigan American College of Emergency
    Medicine Conference, 2004
  • Diastolic Dysfunction
  • Diminished compliance Diastolic dysfunction
    gt40
  • Elderly females
  • Impaired compliance chamber narrowed
  • Concentric hypertrophy
  • Cardiomegaly absent
  • Hypertensive in nature
  • Audible S 4

11
Evidenced Based Medicine
  • Focus was on contractility and hemodynamics
  • Focus now is on neuroendocrine activation,
    remodeling, ventricular shape, left bundle branch
    blocks (LBBB), conduction delays and prolonged
    QRS
  • Albert, N. Critical Care Nurse Supplement, June
    2003.

12
Clinical Challenges in Heart Failure
  • Diagnosis of heart failure
  • Assess the severity of heart failure
  • Assess the progression of heart failure
  • Assessment of treatment efficacy

13
Observation Unit Heart Failure Protocol Entry
Criteria
  • Must have at least 1 from each category
  • 1. B-type natriuretic peptide gt 100 pg/mL
  • 2. History
  • a. Orthopnea
  • b. Dyspnea on exertion
  • c. Paroxysmal nocturnal dyspnea
  • d. Shortness of breath
  • e. Swelling of legs or abdomen
  • f. Weight gain
  • 3. Exam
  • a. Jugular venous distension or elevation
    in pulsation
  • b. Positive abdominal jugular reflux
  • c. S3/S4
  • d. Inspiratory rales
  • e. Peripheral edema
  • 4. Chest X-Ray
  • a. Cardiomegaly
  • b. Pulmonary vascular congestion

Peacock, Frank W.and Albert, N. Reviews in
Cardiovascular Medicine. 2002. Volume 3
Supplement 4 Page S44.
14
Treating the Problem
  • COPD/ pneumonia
  • Beta agonist inhalers
  • Fluids
  • Antibiotics
  • Steroids
  • Acute heart failure
  • Beta blockers
  • Diuretics
  • Recombinant hBNP
  • Vasodilators
  • Restrict sodium

15
Near Patient Testing
16
Characteristics of an Ideal Marker for HF
  • Facilitates diagnosis (highly sensitive,
    specific)
  • Reliable irrespective of age, race/ethnicity, or
    etiology of HF
  • Provides independent prognostic information
  • Changes in patients clinical condition
    correlates with changes in the biomarker
  • Is readily reproducible across laboratories
  • Is available at bedside or in the office to guide
    therapeutic decision making

Bozkurt B Circulation 2003 107 1231-1233
17
Natriuretic Peptides
18
BNP Relationship to NYHA
Objective Vs. Subjective Evaluation Linear Range
5 pg/ml-5000 pg/ml
Triage BNP package insert. Data on File at
Biosite Diagnostics Inc.
19
Secretion
  • BNP
  • secreted from cardiomyocytes
  • an active hormone providing compensatory response
    to the overload in the ventricles
  • released in order decrease fluid volume and
    reduce overload
  • NT-proBNP
  • secreted from cardiomyocytes at the same time as
    BNP
  • Not a hormone, does not assist in decreasing
    fluid volume
  • Inactive protein, requires adequate kidney
    function for clearance from the bloodstream
    making it questionable for patients with
    coexisting renal insufficiency

20
Clearance
  • NT-proBNP is cleared
  • Through the kidneys and is treated as a waste
    product
  • BNP is cleared by
  • Binding to natriuretic peptide receptors
  • Enzymatic degradation

21
CHF and Kidney Disease
  • Dramatic Preponderance of Disease Overlap
  • CRD Overlap has been estimated 30-50 of CHF

CRD
CHF
22
BNP Utilization.Evidence Based
  • Diagnosis of Heart Failure
  • Assessment of HF Disease Severity
  • Risk Stratification of Patients with Acute
    Coronary Syndromes
  • Risk Stratification of Patients with Heart
    Failure
  • Aid in assessment of diastolic dysfunction

23
Accident and Emergency Assessment of Heart Failure
24
BNP Consensus Guidelines
Treatment Options for HF With BP gt90 Diuretics
plus nestiride, especially with CKD and pulmonary
congestion consider adding vasodilators if
hypertensive consider adding inotropes for poor
perfusion
Patient presenting with dyspnea
Treatment Options (cardiac) Consider acute
coronary syndromes
Physical examination, chest X-ray, ECG, BNP
level
BNP lt100 pg/mL
BNP 100500 pg/mL
BNP gt500 pg/mL
HF very unprobable (2)
HF very probable (95)
Clinical suspicion of HF or past history of HF?
HF probable (90)
Treatment Options (noncardiac) Consider COPD
pulmonary embolism asthma pneumonia sepsis
Treatment Options for HF With BP lt90 or
Shock Diuretics, inotropes, vasodilators and/or
nesiritide to follow
Treatment Options Diuretics as required
consider nesiritide if pulmonary congestion, or
for borderline hemodynamic instability, Creat
gt1.5 mg/dL, CrCl lt60 mL/min, BUN gt40 mg/dL
Silver MA et al. Congest Heart Fail. 200410(5
suppl 3)130.
25
Rapid Measurement of B-type Natriuretic Peptide
in the Emergency Diagnosis of Heart Failure
  • Publication New England Journal of Medicine
  • Purpose To validate and characterize the use of
    BNP levels in the diagnosis of CHF
  • Alan S. Maisel, M.D., F.A.C.C., Principal
    Investigator
  • Peter A. McCullough, M.D., M.P.H., F.A.C.C.,
    Co-Principal Investigator

26
Study Design / Methods
  • 7 Field Centers from three countries
  • Prospective study of 1586 patients who presented
    to ED with dyspnea
  • BNP measurement obtained during the initial ED
    evaluation
  • BNP results were blinded to physicians
  • ED Physicians were asked to assign a value of 0
    to 100 of clinical certainty of HF

27
BNP vs NHANES and FraminghamCriteria
Comparative Accuracy
28
Conclusions
  • BNP measurements will improve the ability of
    clinicians to differentiate patients with dyspnea
    due to CHF from those with dyspnea due to other
    causes in acute care settings
  • Mean BNP values reflect functional class in those
    with heart failure
  • BNP has a high degree of sensitivity, specificity
    and accuracy for the diagnosis of heart failure

29
B-Type Natriuretic Peptide and Clinical Judgment
in Emergency Diagnosis of Heart Failure
  • Analysis From Breathing Not Properly (BNP)
    Multinational Study
  • Purpose Determine the degree to which B-type
    natriuretic peptide (BNP) adds to clinical
    judgment in the diagnosis of CHF
  • McCullough, et al
  • Circulation, Vol.106, No 4, 2002

30
FREQUENCY HISTOGRAM
Pre Test Probability of CHF (Blinded to BNP)
31
Conclusions
  • BNP can add to clinical judgment and enhance
    diagnostic accuracy in patients with acute
    dyspnea
  • BNP can clarify the diagnosis when clinical
    indecision exists

32
Risk Stratification with ACS
33
Acute Coronary Syndromes
  • Unstable Angina (UA)
  • Non ST-Segment Myocardial Infarction (NSTEMI)
  • ST-Segment Elevation Myocardial Infarction
    (STEMI)

34
Professional Guidelines Have Been Established
for AMI Management
  • Diagnosis of AMI based on at least 2 of 3
    criteria
  • A clinical history of ischemic-type chest
    discomfort
  • Changes in serially obtained ECG tracings
  • Temporal changes in cardiac markers
  • Initial patient evaluation within 20 minutes of
    ED arrival
  • Door to needle time lt 30 minutes
  • Turn around Time (TAT) for cardiac markers should
    be 30 minutes
  • Percutaneous Coronary Intervention/PTCA 60-90
    minutes

WHO, AHA, ACC, NACB
35
The Prognostic Value of B-Type Natriuretic
Peptide in Patients with Acute Coronary Syndromes
  • Purpose To evaluate the prognostic utility of
    BNP in ACS
  • de Lemos, J.S. et al
  • New England Journal of Medicine
  • October, 2001

36
Study Design/Methods
  • 2525 patients from the TIMI (Thrombolysis in
    Myocardial Infarction) 16 trial included
  • Specimens obtained at 40 /-20 hours after onset
    of ischemic symptoms
  • End points of death or nonfatal MI were evaluated
    at 30 days and 10 months

37
Survival by BNP Quartile Analysis
De Lemos, et al. N England J Med, Vol 345, No.
14, 2001
38
Conclusions
  • BNP provides powerful risk stratification
    information across a spectrum of Acute Coronary
    Syndromes (ACS)
  • BNP of 80 pg/ml is an appropriate risk threshold
    among patients with ACS
  • Prognosis via neurohormonal activation (BNP) are
    distinct from those of myocyte necrosis (TnI)
  • BNP measurement should be considered after an
    ACS in order to identify patients at high and low
    risk for adverse outcomes. Treatments including
    increased surveillance, pharmacologic and
    interventional therapy should be adjusted
    accordingly

39
BNP A Novel blood early blood marker of Acute
MI in patients with chest pain and no ST elevation
  • Publication European Heart Journal
  • Purpose To evaluate BNP for risk assessment
    with non-diagnostic EKG
  • Bassan R. et al.

  • 2004


40
Bassan BNP and AMI
  • 631 patients studied with no ST segment elevation
  • BNP cutoff used was 100 pg/ml
  • BNP identified 22 more of the 72 patients with
    AMI at admission than CKMB/trop alone
  • For patients with a normal troponin at first
    draw, an elevated BNP conferred a 6 times higher
    risk of AMI

Bassan R. et al. European Heart Journal Dec 1 2004
41
BNP Levels on Admission in Chest Pain Patients
SENSITIVITY FOR A.M.I.
100
N 631 patients without ST- segment elevation
(95 CI)

p 0.0000 (in relation to CKMB/cTnI)

75
71
51
50
46
0
BNP gt 100 pg/ml
CKMB gt 5.0 ng/ml
cTnI gt1.0 ng/ml
Bassan et al, EHJ 2005 26 234-240
42
Study Conclusions
  • In patients with chest pain and no STsegment
    elevation
  • Admission BNP has significantly better
    sensitivity than admission CKMB or TnI for AMI
  • Similar NPV for all three markers
  • The combined use of admission BNP, CKMB and
    roponin-I are additive
  • Sensitivity (87, p 0.0000)
  • NPV (97, p lt 0.002) for A.M.I.
  • An elevated admission BNP is an independent
    predictor of AMI in this population
  • In chest pain patients without STEMI admission
    BNP seems to have an adjunctive role for the
    immediate identification and exclusion of A.M.I.

Bassan et al, EHJ 2005 26 234-240
43
Predischarge B-Type Natriuretic Peptide (BNP)
Assay for Identifying Patients at High Risk of
Readmission After Decompensated Heart Failure
  • Purpose To determine if predischarge BNP
    measurements assist in predicting post discharge
    outcomes of patients admitted for decompensated
    heart failure.
  • Logeart D., et al
  • Journal of American College of Cardiology
  • 2004

44
ANALYSIS
93 risk (31 1 month)
60 risk
Death or readmission at 6 months
  • 16 risk

Treatment intensification /or home-based
intervention might be considered for patients at
higher risk (BNP gt 350 pg/mL)
45
Conclusion
  • Predischarge BNP testing in patients admitted
    congestive heart failure (CHF) provides a strong,
    independent indicator of death or readmission and
    is more relevant than common clinical or
    echocardiographic parameters
  • Study results suggest that the use of
    predischarge BNP testing as part of routine
    discharge orders for this population may be
    beneficial

46
Heart Failure in the CommunityWho is watching
the playground?
47
Utility of BNP in the Physician Office
Targets in Treatment
  • In many conditions treatment can be titrated
    againsta target
  • Hypertension Blood Pressure
  • Diabetes Blood Sugar HbAlc
  • Hypercholesterolemia Cholesterol
  • Targets must be objective, reliable, practical
    and cost effective

48
Heart Failure Treatment Targets
There is no target for treatment of heart failure
used routinely in a physicians office that is
  • Objective
  • Reliable
  • Practical
  • Cost effective

49
BNP Guided Management of HF in the Clinic
  • 69 patients with impaired systolic function (LVEF
    lt40) and symptomatic heart failure (NYHA II-IV)
  • Randomized to receive treatment guided by either
    plasma N-BNP concentration or standardized
    clinical assessment

P0.03
60
50
40
Death, Hospitalization, Decompensation
30
  • Follow-up minimum 6 months, median 9.5 months
  • Endpoints death, hospitalization, or heart
    failure decompensation

20
10
0
BNP Group
Clinical Group
Troughton RW et al, Lancet. 2000 Apr
1355(9210)1112-3.
50
Effects of Valsartan on Circulating Brain
Natriuretic Peptide and Norepinephrine in
Symptomatic Chronic heart Failure The Valsartan
Heart Failure Trail (Val-HeFT)
  • Purpose To determine if plasma BNP levels is
    related to severity of HF and is an independent
    predictor of outcomes in HF
  • Latini R, et al
  • Circulation
  • Vol. 106, No. 19, 2002.

51
Study Design/Methods
  • Plasma BNP is strongly related to severity of HF
    and isan independent predictor of outcomes in HF
  • Long term effects of ARBs on BNP in patients with
    HFare not known
  • BNP levels were measured in 4,284 patients
    randomized to valsartan or placebo

Latini, R., Masson S., et al. Circulation, Vol.
106, No. 19, 2002
52
Change in Plasma BNP Over Time
(N 844)
PlaceboBaseline 177.6
(N 1710)
20
10
(N 1890)
0
P lt 0.001
P lt 0.001
in Plasma BNP (pg/mL)
P lt 0.001
-10
ValsartanBaseline 183.5
-20
-30
(N 1850)
(N 1633)
(N 823)
-40
24
0
4
12
Time (months)
Mean SEM.
Latini, R., Masson S., et al. Circulation, Vol.
106, No. 19, 2002
53
Conclusions
  • In the largest neurohormonal study in patients
    withmild to moderate HF, BNP rose progressively,
    consistentwith progressive deterioration of HF

54
Optimal Medical Management for patients with
advanced LV Systolic Dysfunction
  • Core oral pharmacologic therapies
  • Angiotensin-converting enzyme inhibitor at target
    dose
  • Beta-blocker at target dose
  • Digoxin at low dose
  • Spironolactone at low dose
  • Loop diuretic at dose to maintain euvolemia
  • Nonpharmacolgic therapies
  • 2000-mg sodium diet
  • Daily weight monitoring
  • Daily activity and exercise
  • Fluid restriction (if persistent hypervolemia and
    hyponatremia)
  • Surgical therapies
  • Coronary artery revascularization
  • Repair of Mitral Regurgitation
  • Replacement of aortic valve

55
A Look at the Future
(Mars 2004)
56
New Advances for Treating Heart Failure
  • Biventricular Devices
  • Cardiac resynchronization therapy
  • Implantable hemodynamic monitor
  • Angiogenesis
  • Proteomics
  • Percutaneous ventricular assist device (pVAD)
  • Steefel, L Nursing Spectrum, Feb 23, 2003
  • Abraham W.T., et al. Cardiac Therapies in
    Chronic Heart Failure., NEJM 2002 3461845-1853.

57
Future Markers for Risk StratificationCAD - ACS
- CHF
Clinical Condition
Biochemical Marker
Clinical Value
Coronary Artery Disease
Lipids, CRP, Imaging
Risk of event (CAD)
Detection of unstable plaque
MPO, MMPs
Hospital Stayfor ACS
58
  • 9 Cardiologists and
  • 3 Emergency Physicians
  • 4 month Internet writing
  • Followed by a consensus panel meeting
  • Further refinements and publication ready
  • Topical
  • 153 references

Silver MA et al. Congest Heart Fail. 200410(5
suppl 3)130.
59
Adhere National Registry
  • The Adhere Registry Core Module (CM) is the
    observational registry of the management of
    patients treated in-hospital for acute HF
  • The Adhere Registry Longitudinal Module (LM) is a
    prospective registry of severe heart failure
    patients in the outpatient setting
  • The Adhere Registry Emergency Module (EM) is a
    comprehensive registry of heart failure patients
    initially treated in the emergency department to
    improve disease management.

60
Biosite Incorporated
  • Discovery of novel protein-based markers for
    chronic, debilitating and life-threatening
    diseases
  • Development of rapid, bedside tests to support
    clinical practice
  • Drug Toxicology
  • Acute Myocardial Infarction/
    Acute Coronary Syndrome
    (MPO pending)
  • Heart Failure
  • Shortness of Breath Panel
  • D-dimer
  • Stroke (pending)
  • Sepsis (pending)

61
Triage BNP Highlights
  • Triage BNP is indicated as an aid in the
    diagnosis of heart failure, severity of disease,
    and for risk stratification for ACS. (Linear
    range 5-5000 pg/ml)
  • Diagnosis of patients presenting with
    non-specific symptoms associated with HF,
    including SOB, edema, fatigue, nausea or
    suspected diastolic heart failure
  • No interference with typically prescribed heart
    related drugs
  • No statistically significant changes in BNP
    concentrations with hypertension, diabetes, renal
    insufficiency COPD
  • 100 pg/ml has general specificity of 98 and
    negative predictive values greater than 981
  • Available for Outpatient setting, A E, Chest
    Pain Unit, and In-patient arena.

Triage BNP package insert. Data on File at
Biosite Diagnostics Inc. 1 Dao Q, Krishnaswamy
P, Kazanegra R, Harrison A et al. Journal of the
American College of Cardiology 2001 37
379-385. 2 Triage BNP Package Insert. 3
Lubien E, DeMaria A, Krishnaswamy P, Clopton P,
et al. Circulation 105 595-601. 4 De Lemos J,
Morrow D, et al. The New England Journal of
Medicine 2001 345 1014-1021.
62
Thank youfor your kind attention!International
Liaison for the American Association of Heart
Failure Nurseswww.aahfn.org
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