ACEP Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting...

ACEP Clinical Policy: Critical Issues in the Evaluation

and Managementof Adult Patients Presenting to the

Emergency Department withAcute Heart Failure Syndromes

ACEP Clinical Policy: Critical Issues in the Evaluation

and Managementof Adult Patients Presenting to the

Emergency Department withAcute Heart Failure Syndromes

Brian McMichael, M.D.PGY-1, Emergency Medicine

Wayne State University/Detroit Medical Center (Detroit Receiving Hospital)

Brian McMichael, M.D.PGY-1, Emergency Medicine

Wayne State University/Detroit Medical Center (Detroit Receiving Hospital)

ObjectivesObjectives

Give an overview of the pathophysiology of responses that lead to the common final pathway of acute heart failure (AHF) syndromes.

Present key treatment modalities for AHF. Present the findings of the ACEP Clinical Policy Consider rational interventional approaches that

take into account evidence and the particularities of patient history and physical upon presentation.

Give an overview of the pathophysiology of responses that lead to the common final pathway of acute heart failure (AHF) syndromes.

Present key treatment modalities for AHF. Present the findings of the ACEP Clinical Policy Consider rational interventional approaches that

take into account evidence and the particularities of patient history and physical upon presentation.

GoalsGoals

Participants will be able to understand the four core questions of the ACEP Clinical Policy

Participants will be able to understand the best supported conclusions to the four core questions

Participants will be able to formulate treatment approaches likely to be most effective for a given history and physical of patient scenarios.

Participants will be able to understand the four core questions of the ACEP Clinical Policy

Participants will be able to understand the best supported conclusions to the four core questions

Participants will be able to formulate treatment approaches likely to be most effective for a given history and physical of patient scenarios.

PerspectivePerspective

Prevalence: 5,000,000– ~ 2 % of total US population

Incidence: 550,000– Approaches 10 per 1000 for those > 65 yrs

Prevalence: 5,000,000– ~ 2 % of total US population

Incidence: 550,000– Approaches 10 per 1000 for those > 65 yrs

American Heart Association. Heart Disease and Stroke Statistics - 2004 Update.

5.86.2

9.8

1.5

0.3 0.5

1.82.3

10.9

4.1

0.40.3

-1

1

3

5

7

9

11

20-34 35-44 45-54 55-64 65-74 75+

Ages

Percent of Population

Men Women

Prevalence by Age and GenderPrevalence by Age and Gender


Perspective: Hospital CarePerspective: Hospital Care

Total hospital discharges in 2001: 995,000– 164 % increase from 1979– Most common DRG among pts > 65

Total hospital discharges in 2001: 995,000– 164 % increase from 1979– Most common DRG among pts > 65


0

100

200

300

400

500

600

700

79 80 85 90 95 00 03

Years

Discharges in Thousands

Male Female

Who is at Risk for Heart Failure Development? 1,2

Who is at Risk for Heart Failure Development? 1,2

Overall, lifetime risk is 1 in 5 for those > 40 yrs HTN and CAD are primary risk factors

– Risk ↓ to 1 in 9 for males and 1 in 6 for females without hx of CAD

– HTN antedates disease onset in 75% Chronic BP ≥ 160/100: risk ~ 1 in 4 Chronic BP < 140/90: risk ~ 1 in 8

Overall, lifetime risk is 1 in 5 for those > 40 yrs HTN and CAD are primary risk factors

– Risk ↓ to 1 in 9 for males and 1 in 6 for females without hx of CAD

– HTN antedates disease onset in 75% Chronic BP ≥ 160/100: risk ~ 1 in 4 Chronic BP < 140/90: risk ~ 1 in 8

1 Lloyd-Jones DM, et al. Circulation. 2002;106:3068-72.2 Levy D, et al. JAMA 1996;275(20):1557-62.

Disproportionate Risk for African-Americans 1-5

Disproportionate Risk for African-Americans 1-5

50-75% excess rate of new-onset HF Younger age with more advanced disease

at initial presentation More rapid progression from asymptomatic

to symptomatic phase

50-75% excess rate of new-onset HF Younger age with more advanced disease

at initial presentation More rapid progression from asymptomatic

to symptomatic phase

1 McCullough PA, et al. J Am Coll Cardiol 2002;39(1):60-9.2 Yancy CW. Curr Cardiol Rep 2002;4(3):218-25.3 Yancy CW. Curr Cardiol Rep 2001;3(3):191-7.4 Bourassa MG, et al. J Am Coll Cardiol 1993;22(4 Suppl A):14A-9A.5 Afzal A, et al. Clin Cardiol 1999;22(12):791-4.

Disproportionate RiskDisproportionate Risk

May be explained by divergence in etiology 1-3

– Hypertensive cardiomyopathy in AA– Ischemic cardiomyopathy in Caucasians

May be explained by divergence in etiology 1-3

– Hypertensive cardiomyopathy in AA– Ischemic cardiomyopathy in Caucasians

1 Bourassa MG, et al. J Am Coll Cardiol 1993;22(4 Suppl A):14A-9A.2 Alexander M, et al. JAMA 1995;274(13):1037-42.3 Mathew J, et al. Am J Cardiol 1996;78(12):1447-50.

DMC StatisticsDMC Statistics

Total ED visits for HF 1999-2004 Total ED visits for HF 1999-2004

Site 1999 2000 2001 2002 2003 2004ALL

YEARS

DRH 1,044 1,055 1,243 1,151 1,125 1,117 6,735

HARPER 712 784 726 797 786 794 4,599

HVSH 365 433 453 494 490 446 2,681

SGH 1,589 1,609 1,504 1,439 1,375 1,475 8,991

TOTAL 3,710 3,881 3,926 3,881 3,776 3,83223,00

6

Perspective: Bottom LinePerspective: Bottom Line


142.5

57.9 63.5

29.6

020406080100120140160

Coronary Heart Disease

Stroke

Hypertensive Disease

Heart FailureB

illions of Dollars

What is Heart Failure ?What is Heart Failure ?

Syndrome defined by inadequate cardiac performance– Primarily a reflection of ventricular dysfunction

Diminished inotropy (systolic ~ 55 %) Diminished compliance (diastolic ~ 45 %)

– Exacerbated by changes in volume status

Syndrome defined by inadequate cardiac performance– Primarily a reflection of ventricular dysfunction

Diminished inotropy (systolic ~ 55 %) Diminished compliance (diastolic ~ 45 %)

– Exacerbated by changes in volume status

Starling CurveStarling Curve

LV End-Diastolic Volume (or Pressure)

Stroke

Volume

Normal response

Baseline

Heart failure

Normal Pressure-Volume LoopNormal Pressure-Volume Loop

LV Volume

LV

Pressure SV

Compliance

Inotropy

4. AV Closes

3. AV Opens

2. MV Closes

1. MV Opens

Normal Pressure-Volume LoopNormal Pressure-Volume Loop

LV Volume

LV

Pressure

EDVESV

SVCompliance

Inotropy

EDP

Systolic DysfunctionSystolic Dysfunction

LV Volume

LV

Pressure

Diastolic DysfunctionDiastolic Dysfunction

LV Volume

LV

Pressure

More on Etiology of Cardiac Dysfunction

More on Etiology of Cardiac Dysfunction

Systolic– Males 50-70– Impaired contractility– Chamber dilated – Eccentric hypertrophy– Cardiomegaly noted– Ischemic in nature – Audible S3

Limited ability to differentiate based solely on clinical parameters 1

Systolic– Males 50-70– Impaired contractility– Chamber dilated – Eccentric hypertrophy– Cardiomegaly noted– Ischemic in nature – Audible S3

Limited ability to differentiate based solely on clinical parameters 1

Diastolic– Elderly females– Impaired compliance– Chamber narrowed– Concentric hypertrophy– Cardiomegaly absent– Hypertensive in nature– Audible S4

Diastolic– Elderly females– Impaired compliance– Chamber narrowed– Concentric hypertrophy– Cardiomegaly absent– Hypertensive in nature– Audible S4

1 Thomas et al. Am J Med 2002;112:437-45.

General PrinciplesGeneral Principles

Focus is on clinical presentation not etiology 1,2

– Common denominator = ↑ LVEDP

– End result = congestion

Balance specificity with sensitivity– Rule-out vs. rule-in approach

Focus is on clinical presentation not etiology 1,2

– Common denominator = ↑ LVEDP

– End result = congestion

Balance specificity with sensitivity– Rule-out vs. rule-in approach

1 Gheorghiade et al. Circulation 2005;112:3958-68.2 Friedewald et al. Am J Cardiol 2007;10:1145-52.

Basic PathophysiologyBasic Pathophysiology

Cardiac dysfunction leads to diminished output with arterial underfilling – Baroreceptor activation

Carotid sinus Left ventricle Aortic arch

– ↓ glomerular filtration rate Triggers compensatory response

Cardiac dysfunction leads to diminished output with arterial underfilling – Baroreceptor activation

Carotid sinus Left ventricle Aortic arch

– ↓ glomerular filtration rate Triggers compensatory response

Basic PathophysiologyBasic Pathophysiology

From: Schrier and Abraham. NEJM 1999;341:583.

Compensatory ResponseCompensatory Response

Enhanced sympathetic tone– Predominantly norepinephrine 1,2

– Improves circulatory integrity ↑ inotropy and chronotropy (β1) ↑ preload and afterload (α1) ↑ effective volume (α1)

– Beneficial effects ↓ over time Receptor down-regulation and G-protein uncoupling Induction of myocyte toxicity 3,4

Enhanced sympathetic tone– Predominantly norepinephrine 1,2

– Improves circulatory integrity ↑ inotropy and chronotropy (β1) ↑ preload and afterload (α1) ↑ effective volume (α1)

– Beneficial effects ↓ over time Receptor down-regulation and G-protein uncoupling Induction of myocyte toxicity 3,4

1 Braunwald et al. Proc R Soc Med 1965;58:1063-6.2 Francis et al. Ann Intern Med 1984;101:370-7.3 Schrier et al. NEJM 1999;341:577-84.4 Mann et al. Circulation 1992;85:790-804.

Biochemical Response to Adrenergic Stimulation

Biochemical Response to Adrenergic Stimulation

Compensatory ResponseCompensatory Response

Stimulation of neurohormonal modulators– Renin-angiotensin-aldosterone system (RAAS)– ANP– Arginine vasopressin

Cytokine release

Stimulation of neurohormonal modulators– Renin-angiotensin-aldosterone system (RAAS)– ANP– Arginine vasopressin

Cytokine release

RAASRAAS

Renin

Angiotensinogen

Active angiotensin fragments: Ang III, Ang IV, Ang 1-7

Angiotensin II

Angiotensin I

ACE (Lung, etc)

Chymase, other proteases

Protease

Direct effects of AT II

Bradykinin

Inactive kinins

Angiotensin-IIAngiotensin-II

Vasoconstriction– Efferent > afferent arteriolar constriction

Results in ↑ GFR

Promotion of sodium reabsorption– Direct effect on proximal tubule – Indirect through stimulation of aldosterone

release Dipsogenic response Cardiac (and vascular) remodeling

Vasoconstriction– Efferent > afferent arteriolar constriction

Results in ↑ GFR

Promotion of sodium reabsorption– Direct effect on proximal tubule – Indirect through stimulation of aldosterone

release Dipsogenic response Cardiac (and vascular) remodeling

AldosteroneAldosterone

Sodium (and water) reabsorption at collecting ducts– Typical effect on extracellular volume ~ 2 L– Regulated by intrinsic feedback 1

Based on distal sodium delivery Altered in heart failure; results in sodium and fluid

retention

Diminishes arterial compliance Stimulates myocyte collagen synthesis 2

Sodium (and water) reabsorption at collecting ducts– Typical effect on extracellular volume ~ 2 L– Regulated by intrinsic feedback 1

Based on distal sodium delivery Altered in heart failure; results in sodium and fluid

retention

Diminishes arterial compliance Stimulates myocyte collagen synthesis 2

1 Schrier et al. NEJM 1999;341:577-84.2 Cohn et al. J Am Coll Cardiol 2000;35:569-582.

Arginine VasopressinArginine Vasopressin

Vasoconstriction (V1A receptor) Antidiuresis (V2 receptor)

– Occurs in collecting ducts– Induces synthesis and translocation of

aquaporin-2 water channels Suppressed by atrial stretch receptors

– Impaired in heart failure, with free-water retention

Vasoconstriction (V1A receptor) Antidiuresis (V2 receptor)

– Occurs in collecting ducts– Induces synthesis and translocation of

aquaporin-2 water channels Suppressed by atrial stretch receptors

– Impaired in heart failure, with free-water retention

Nielsen et al. Proc Natl Acad Sci USA 1995;92:1013-7.

Cytokine Mediators 1,2Cytokine Mediators 1,2

Proinflammatory– Triggered by myocardial inflammation– ? role of endotoxin from hypoperfused intestines

Tumor necrosis factor (TNF-α) Transforming growth factor β (TGF- β) Interleukins (IL-1,2 and 6) Intracellular adhesion molecules (ICAM)

Vasoactive– Endothelin (ET)

Proinflammatory– Triggered by myocardial inflammation– ? role of endotoxin from hypoperfused intestines

Tumor necrosis factor (TNF-α) Transforming growth factor β (TGF- β) Interleukins (IL-1,2 and 6) Intracellular adhesion molecules (ICAM)

Vasoactive– Endothelin (ET)

1 Anker et al. Heart 2004;90:464-70.2 Aukurst et al. Autoimmunity Reviews 2004;3:221-7.

Endothelin: Receptors & Effects Endothelin: Receptors & Effects

ETA (upregulated)– Vasoconstriction (pulmonary HTN)– Smooth muscle and myocyte hypertrophy– ↑ inotropy and chronotropy– ↑ sodium and water retention

ETB (downregulated)– Vasodilation– ↑ aldosterone production– ↑ ET-1 clearance and autocrine regulation

ETA (upregulated)– Vasoconstriction (pulmonary HTN)– Smooth muscle and myocyte hypertrophy– ↑ inotropy and chronotropy– ↑ sodium and water retention

ETB (downregulated)– Vasodilation– ↑ aldosterone production– ↑ ET-1 clearance and autocrine regulation

Spieker et al. J Am Coll Cardiol 2001;37:1493-1505.

Ventricular RemodelingVentricular Remodeling

Gradual response to initial insult, circulating factors and oxidative stress

Cycle leading to progressive dysfunction

Gradual response to initial insult, circulating factors and oxidative stress

Cycle leading to progressive dysfunctionInsult with

myocyte necrosis Hypertrophy

of remaining cells

Fibroblast proliferation with collagen synthesis

Collagen degradation

with progressive fibrosis

Myocyte apoptosi

s

Cohn et al. J Am Coll Cardiol 2000;35:569-582.

Ventricular Remodeling: Translational Model

Ventricular Remodeling: Translational Model

Hunter and Chien. NEJM 1999;341:1276-1283.

From: Jessup et al. N Engl J Med 2003;348:2007-2018.

Myocyte elongation

Infarct Related RemodelingInfarct Related Remodeling

Ischemic RemodelingIschemic Remodeling

Wall thinning may cause chordae retraction – Result = ischemic mitral valve requrgitation

Wall thinning may cause chordae retraction – Result = ischemic mitral valve requrgitation

Bursi et al. Am J Med 2006;119:103-12.

From: Jessup et al. N Engl J Med 2003;348:2007-2018.

“Eccentric” Hypertrophy

“Concentric” Hypertrophy

Non-infarct Related Remodeling

Non-infarct Related Remodeling

Counter RegulationCounter Regulation

Stimulation of natriuretic peptide system– A-type or atrial (ANP) and B-type or brain

(BNP) most important– Produce diuresis, natriuresis and

vasodilation

Release of coenzyme Q10

– Enhances mitochondrial function

Stimulation of natriuretic peptide system– A-type or atrial (ANP) and B-type or brain

(BNP) most important– Produce diuresis, natriuresis and

vasodilation

Release of coenzyme Q10

– Enhances mitochondrial function

CHF and Na+ RetentionCHF and Na+ Retention

Counter RegulationCounter Regulation

Release of endogenous vasodilators– Prostacyclin and prostaglandin E– Bradykinin – Nitric oxide (NO)

Produced from L-arginine by NO synthetase – Soluble or bound form (endothelial cells)

Induces smooth muscle relaxation via cGMP Tenuous balance

Release of endogenous vasodilators– Prostacyclin and prostaglandin E– Bradykinin – Nitric oxide (NO)

Produced from L-arginine by NO synthetase – Soluble or bound form (endothelial cells)

Induces smooth muscle relaxation via cGMP Tenuous balance

Nitric Oxide BalanceNitric Oxide Balance

Hare, JM. NEJM 2004;351:2112-2114.

Contributory Cellular Mechanisms

Contributory Cellular Mechanisms

Disruptions of cytoskeletal and contractile proteins 1

Sodium channel ion channel mutations 2

– SCN5A associated with dilated cardiomyopathy

KATP regulatory subunit defects 3

Altered intracellular calcium cycling 4,5

Disruptions of cytoskeletal and contractile proteins 1

Sodium channel ion channel mutations 2

– SCN5A associated with dilated cardiomyopathy

KATP regulatory subunit defects 3

Altered intracellular calcium cycling 4,5

1 Schonberger and Seidman. Am J Hum Genet 2001;69:249-60.2 Olson et al. JAMA 2005;293:447-54.3 Bienengraeber et al. Nat Genet 2004;36:382-87.4 Schmitt et al. Science 2003;299:1410-3.5 Wehrens et al. Science 2004;304:292-6.

Calcium Cycle ModulationCalcium Cycle Modulation

Renlund, DG. N Engl J Med 2004;351:849-851.

Heart Failure PresentationsHeart Failure Presentations

Fatigue Right-sided features

– Peripheral edema– Ascites

Left-sided features– Dyspnea (exertional or nocturnal)– Rales– Acute cardiogenic pulmonary edema (ACPE)

Fatigue Right-sided features

– Peripheral edema– Ascites

Left-sided features– Dyspnea (exertional or nocturnal)– Rales– Acute cardiogenic pulmonary edema (ACPE)

CardioRenal SyndromeCardioRenal Syndrome

Heart failure plus– Chronic renal insufficiency– Worsening renal function during treatment

25% or > increase in Cr or BUN

– Difficult diuresis w/o worsening renal function– ACE (-) intolerance from hypotension or

hyperkalemia

Often complicated by anemia

Heart failure plus– Chronic renal insufficiency– Worsening renal function during treatment

25% or > increase in Cr or BUN

– Difficult diuresis w/o worsening renal function– ACE (-) intolerance from hypotension or

hyperkalemia

Often complicated by anemia

Diagnosis of Heart FailureDiagnosis of Heart Failure

Can be difficult on clinical basis alone– Limited sensitivity of physical examination 1,2

– Electrocardiogram often not helpful 3,4

– Common chest x-ray findings unreliable and often non-predictive 5

Cepahalization Cardiomegaly Interstitial edema

Can be difficult on clinical basis alone– Limited sensitivity of physical examination 1,2


– Common chest x-ray findings unreliable and often non-predictive 5

Cepahalization Cardiomegaly Interstitial edema

1 Stevenson et al. JAMA 1989;261:884-82 Badgett et al. JAMA 1997;277:1712-9.3 Davie et al. BMJ 1996;312:222.4 Gillespie et al. BMJ 1997;314:936-940.5 Badgett et al. J Gen Intern Med 1996;11:625-634.

Diagnosis of Heart FailureDiagnosis of Heart Failure

Difficult based on common variables– Limited sensitivity of physical examination 1,2


Atrial fibrillation may be found in up to 1/3 Interventricular conduction delays in 1/4

– Common chest x-ray findings unreliable and often non-predictive 5,6

Normal in ~ 20%

↑ reliance on serum markers

Difficult based on common variables– Limited sensitivity of physical examination 1,2


Atrial fibrillation may be found in up to 1/3 Interventricular conduction delays in 1/4

– Common chest x-ray findings unreliable and often non-predictive 5,6

Normal in ~ 20%

↑ reliance on serum markers1 Stevenson et al. JAMA 1989;261:884-82 Badgett et al. JAMA 1997;277:1712-9.3Davie et al. BMJ 1996;312:222.4 Gillespie et al. BMJ 1997;314:936-940.5 Badgettet al. J Gen Intern Med 1996;11:625-634.6 Collins et al. Ann Emerg Med 2006;47;13-8.

Criterion Diagnosis of Heart FailureCriterion Diagnosis of Heart Failure

Framingham– Most commonly used– Defines cases as questionable, probable or

definite HF– Definite requires 2 major or 1 major and 2 minor

criteria

National Health and Nutrition Examination Surveys (NHANES)

Boston European Society of Cardiology

Framingham– Most commonly used– Defines cases as questionable, probable or

definite HF– Definite requires 2 major or 1 major and 2 minor

criteria

National Health and Nutrition Examination Surveys (NHANES)

Boston European Society of Cardiology

Framingham Criteria 1,2Framingham Criteria 1,2

Major CriteriaClinicalPNDOrthopnea↑ JVPHepatojugular refluxRales

S3 gallop Chest x-ray

CardiomegalyPulmonary edema

Major CriteriaClinicalPNDOrthopnea↑ JVPHepatojugular refluxRales

S3 gallop Chest x-ray

CardiomegalyPulmonary edema

Minor CriteriaAnkle edemaNight cough

Dyspnea on exertionHepatomegaly

Pleural effusionHR ≥ 120Wt loss ≥ 4.5 kg in 5 d Considered major criterion when occurring in response to diuretics

Minor CriteriaAnkle edemaNight cough

Dyspnea on exertionHepatomegaly

Pleural effusionHR ≥ 120Wt loss ≥ 4.5 kg in 5 d Considered major criterion when occurring in response to diuretics

1 McKee et al. NEJM 1971;285:1441-6.2 Kannel et al. Arch Intern Med 1999;159:1197-1204.

Clinical Diagnostic AccuracyClinical Diagnostic Accuracy

Wang et al. JAMA 2005;294:1944-56.

Exam Findings Do MatterExam Findings Do Matter

Drazneret al. NEJM 2001;345:574-81.

Acoustic CardiographyAcoustic Cardiography

http://depts.washington.edu/physdx/heart/tech2.html

Gallop Murmur MnemonicsGallop Murmur Mnemonics S3

Montreal

SLOSH'-ing-in SLOSH'-ing-in SLOSH'-ing-in S1 S2 S3 S1 S2 S3 S1 S2 S3

Kentucky/Tennessee? (you decide)

S3Montreal

SLOSH'-ing-in SLOSH'-ing-in SLOSH'-ing-in S1 S2 S3 S1 S2 S3 S1 S2 S3


S4Toronto

a-STIFF'-wall a-STIFF'-wall a-STIFF'-wall S4 S1 S2 S4 S1 S2 S4 S1 S2


S4Toronto

a-STIFF'-wall a-STIFF'-wall a-STIFF'-wall S4 S1 S2 S4 S1 S2 S4 S1 S2


http://www.ai.rug.nl/~tjeerd/CPSP/app2-1.html

Acoustic Cardiography: Test Characteristics

Acoustic Cardiography: Test Characteristics

Marcus et al. JAMA 2005;295:2238-44.

Ear of the Beholder?Ear of the Beholder?

Marcus et al. Arch Intern Med 2006;166:617-22.

CXR and ECGCXR and ECG

Wang et al. JAMA 2005;294:1944-56.

Serum MarkersSerum Markers

Natriureticpeptides– ANP– N-ANP– BNPBNP– NT-proBNP

Norepinephrine Endothelin Proinflammatorycytokines

– TNF-α, IL-1β, IL-6

Natriureticpeptides– ANP– N-ANP– BNPBNP– NT-proBNP

Norepinephrine Endothelin Proinflammatorycytokines

– TNF-α, IL-1β, IL-6

BNP BNP Level > 100 pg/ml more accurate

than clinical criteria for diagnosis– BNP: 83 %– Framingham: 73 %– NHANES: 67 %

Level > 100 pg/ml more accurate than clinical criteria for diagnosis– BNP: 83 %– Framingham: 73 %– NHANES: 67 %

Robust independent predictive value

Robust independent predictive value

Maisel et al. NEJM 2002;347:161-7.

ROC Curve (BNP)ROC Curve (BNP)

Maiselet al. NEJM 2002;347:161-7.

@ 100 pg/ml cut off:

Sens 90 % Spec 76 PPV 79 NPV 89

BNP: Pooled Operating Characteristics

BNP: Pooled Operating Characteristics

Wang et al. JAMA 2005;294:1944-56.

Should You Obtain a BNP for High Probability Pts ?

Should You Obtain a BNP for High Probability Pts ?

Correlates with disease severity and provides prognostic information 1,2

– BNP > 480 pg/ml 51 % with HF event at 6 mos Rate only 2.5 % when < 230 pg/ml

– BNP > 700 pg/ml HR (death or admit) = 15.2

Enables serial comparison 3

– Inc. risk of death when remains “high” ≥ 97 pg/ml

Correlates with disease severity and provides prognostic information 1,2

– BNP > 480 pg/ml 51 % with HF event at 6 mos Rate only 2.5 % when < 230 pg/ml

– BNP > 700 pg/ml HR (death or admit) = 15.2

Enables serial comparison 3

– Inc. risk of death when remains “high” ≥ 97 pg/ml

1 Harrison et al. Ann Emerg Med 2002;39:131-138.2 Logeart et al. J Am Coll Cardiol 2004;43:635-41.3 Latini et al. Am J Med 2006;119:70.e23-30.

BNP: Using Your Results BNP: Using Your Results

Utilization improves clinical judgment 1

– Degree dependent on pre-test probability

– Effect greatest for “intermediate” pts

Best use: acute dyspnea– Reliably differentiates HF

from lung disease 2

– Can reduce admissions, ICU use and LOS 3

Utilization improves clinical judgment 1

– Degree dependent on pre-test probability

– Effect greatest for “intermediate” pts

Best use: acute dyspnea– Reliably differentiates HF

from lung disease 2

– Can reduce admissions, ICU use and LOS 3

1 McCollough et al. Circulation 2002;106:416-22.2 Morrison et al. J Am Coll Cardiol 2002;39:202-9.3 Mueller et al. NEJM 2004;350:647-54.

BNP: Things to ConsiderBNP: Things to Consider

May be lower than expected with– Flash pulmonary edema

– Diastolic dysfunction

Mild elevation (100-500 pg/ml) found with other conditions– Cor Pulmonale

– PE

– COPD

– Pulmonary HTN

May be lower than expected with– Flash pulmonary edema

– Diastolic dysfunction

Mild elevation (100-500 pg/ml) found with other conditions– Cor Pulmonale

– PE

– COPD

– Pulmonary HTN

Other Natriuretic PeptidesOther Natriuretic Peptides

ANP and N-ANP– Correlates with ↓ LVEF, but lower sensitivity and NPV

than BNP 1

NT-proBNP– Similar overall accuracy to BNP

– May be better predictor of LV dysfunction 2,3

Wall motion index < 1.2or LVEF < 40 %

– Useful as a marker of therapeutic effectiveness 4

ANP and N-ANP– Correlates with ↓ LVEF, but lower sensitivity and NPV

than BNP 1

NT-proBNP– Similar overall accuracy to BNP

– May be better predictor of LV dysfunction 2,3

Wall motion index < 1.2or LVEF < 40 %

– Useful as a marker of therapeutic effectiveness 4

1 Collins et al. Ann Emerg Med 2003;41:532-545.2 Talwar et al. Eur Heart J 1999;20:1736-44.3 Hammerer-Lecher et al. Clin Chim Acta 2001;310:193-7.4 Troughton et al. Lancet 2000;355:1126-30.

NT-proBNPNT-proBNP

Moe et al. Circulation 2007;115:3103-10.

Natriuretic Peptide CaveatsNatriuretic Peptide Caveats Relative increase in women Inverse relationship with BMI

Relative increase in women Inverse relationship with BMI

Krauser et al. Am Heart J 2005;149-744-50.

Natriuretic Peptide CaveatsNatriuretic Peptide Caveats

Daniels et al. Am Heart J 2006;151:999-1005.

Natriuretic Peptide CaveatsNatriuretic Peptide Caveats

Higher with renal dysfunction Higher with renal dysfunction

McCollough et al. Am J Kidney Dis 2003;41:571-9.Anwaruddin et al. JACC 2006;47:91-7.

Optimal cut-point = 200 pg/ml

Optimal cut-point = 1200 pg/ml

EchocardiographyEchocardiography

Gold standard Functional and structural information

– Ejection fraction

– Wall motion

– Tissue doppler and harmonics

– Chamber size

– LV wall thickness and mass

– Regurgitant mitral valve diameter

Utility in acute setting is unclear

Gold standard Functional and structural information

– Ejection fraction

– Wall motion

– Tissue doppler and harmonics

– Chamber size

– LV wall thickness and mass

– Regurgitant mitral valve diameter

Utility in acute setting is unclear

EchocardiographyEchocardiography

Provides long-term prognostic information– Annual mortality with EF ≤ 10 %: ~ 29 % !

Enables diagnosis of HF etiology 1

– Systolic dysfunction: EF < 50 %

– Diastolic dysfunction: EF ≥ 50 % with impaired relaxation and elevation of filling pressures Doppler tissue imaging at mitral annulus

Provides long-term prognostic information– Annual mortality with EF ≤ 10 %: ~ 29 % !

Enables diagnosis of HF etiology 1

– Systolic dysfunction: EF < 50 %

– Diastolic dysfunction: EF ≥ 50 % with impaired relaxation and elevation of filling pressures Doppler tissue imaging at mitral annulus

1 Bursi et al. JAMA 2006;296:2209-2216.

CHF Treatment ModalitiesCHF Treatment Modalities

DiureticsDiuretics

Limited evidence, but used empirically Loop agents most common

– Initial diuresis at 30 min 1

Peak effect at 2-4 hrs Maximal with 160-200 mg furosemide Avg in-hospital net diuresis > 4 L 2

– Vasodilatory effect at 15 min 3

Latent constriction through RAAS and adrenergic activation 4

– ↑ efficacy in combination with thiazides

Limited evidence, but used empirically Loop agents most common

– Initial diuresis at 30 min 1

Peak effect at 2-4 hrs Maximal with 160-200 mg furosemide Avg in-hospital net diuresis > 4 L 2

– Vasodilatory effect at 15 min 3

Latent constriction through RAAS and adrenergic activation 4

– ↑ efficacy in combination with thiazides1 Brater DC. NEJM 1998; 339:387-395.2 Steimle et al. Circulation 1997;96:1165-72.3 Dikshit et al. NEJM 1973;288:1087-90.4 Francis et al. Ann Intern Med 1985;103:1-6.

NitratesNitrates

Recognized benefit since mid-1970’s Produces rapid ↓ in PCWP with clinical

improvement 1

At lower doses, preload reduction through venodilation 2

Arterial dilation with afterload reduction at higher IV doses (≥ 250 mcg/min) 2,3

– Dose-effect relationship – More pronounced with ↑ resistance 4

Recognized benefit since mid-1970’s Produces rapid ↓ in PCWP with clinical

improvement 1

At lower doses, preload reduction through venodilation 2

Arterial dilation with afterload reduction at higher IV doses (≥ 250 mcg/min) 2,3

– Dose-effect relationship – More pronounced with ↑ resistance 4

1 Bussmann et al. Am L Cardiol 1978;41:931-936.2 Imhof et al. Eur J Clin Pharmacol 1980;18:455-60.3 Herling IM. Am Heart J 1984;108:141-9.4 Haber et al. J Am Coll Cardiol 1993;22:251-7.

NitroprussideNitroprusside

Effective in refractory ACPE with ↑ SVR Enables concurrent venous and arterial

dilation Requires arterial line placement for proper

titration Produces reflex tachycardia Potential for cyanide toxicity

– Minimized by use of thiosulfate

Effective in refractory ACPE with ↑ SVR Enables concurrent venous and arterial

dilation Requires arterial line placement for proper

titration Produces reflex tachycardia Potential for cyanide toxicity

– Minimized by use of thiosulfate

Guiha et al. NEJM 1974;291:587-92.

NesiritideNesiritide

Exogenous BNP Rapid onset

– Peak effect in 30 - 60 min

Elimination half-life = 18 min Dosing

– 2 mcg/kg bolus– Infusion at 0.01 mcg/kg/min (titration to a max of 0.03

mcg/kg/min)

Safe with dose dependent ↓ in PCWP

Exogenous BNP Rapid onset

– Peak effect in 30 - 60 min

Elimination half-life = 18 min Dosing

– 2 mcg/kg bolus– Infusion at 0.01 mcg/kg/min (titration to a max of 0.03

mcg/kg/min)

Safe with dose dependent ↓ in PCWP

Colucci et al. NEJM 2000;343:246-53.

ACE InhibitorsACE Inhibitors

Limited data on use in acute setting Sublingual captopril (25 mg) 1,2

– Diminished rate of intubation (9 vs 20 %)– Improved dyspnea scores at 30 min– Early improvements in SVI and CI

IV enalaprilat 3

– Improved hemodynamics with 1 mg infusion– No data on bolus dosing

Limited data on use in acute setting Sublingual captopril (25 mg) 1,2

– Diminished rate of intubation (9 vs 20 %)– Improved dyspnea scores at 30 min– Early improvements in SVI and CI

IV enalaprilat 3

– Improved hemodynamics with 1 mg infusion– No data on bolus dosing

1 Haude et al. Int J Cadiol 1990;27:351-9.2 Hamilton et al. Acad Emerg Med 1996;3:205-212.3 Annane et al. Cirulation 1996;94:1316-24.

Inotropic AgentsInotropic Agents

Usually reserved for those with ↓ CO Dobutamine 1,2

– Increases ventricular ectopy and myocardial oxygen demand

Milrinone 3,4

– Prolonged LOS and ↑ 60-day mortality More pronounced with ischemic etiology

↑ in-hospital mortality for both versus NTG and nesiritide 5

Usually reserved for those with ↓ CO Dobutamine 1,2

– Increases ventricular ectopy and myocardial oxygen demand

Milrinone 3,4

– Prolonged LOS and ↑ 60-day mortality More pronounced with ischemic etiology

↑ in-hospital mortality for both versus NTG and nesiritide 5

1 Leier et al. Circulation 1977;56:468-72..2 Burger et al. Am J Cardiol 2001;88:35-39.3 Cuffe et al. JAMA 2002;287:1541-74 Felker et al. J Am Coll Cardiol 2003;41:997-1003.5 Abraham et al. J Card Fail 2003; 9:S81.

Inotropic AgentsInotropic Agents

Levosimendan – Novel calcium sensitizer

Contractility improvement w/o ↑ O2 consumption

– Opens K-ATP channel – Dose-response relationship with ↑ in CO/SV

and ↓ in PCWP 1,2 – Dosing: IV bolus (6 to 24 mcg/kg) followed by

infusion (0.05 to 0.2 mcg/kg/min)– Trial data promising

Levosimendan – Novel calcium sensitizer

Contractility improvement w/o ↑ O2 consumption

– Opens K-ATP channel – Dose-response relationship with ↑ in CO/SV

and ↓ in PCWP 1,2 – Dosing: IV bolus (6 to 24 mcg/kg) followed by

infusion (0.05 to 0.2 mcg/kg/min)– Trial data promising

1 Nieminen et al. J Am Coll Cardiol. 2000;36:1903-12. 2 Slawsky et al. Circulation 2000;102:2222-7.

Morphine SulfateMorphine Sulfate

Commonly used; limited supporting data Unclear derivation of beneficial effects

– Venodilation – Afterload reduction– Respiratory relaxation

Evidence suggesting association with adverse outcomes 1,2

– ↑ need for intubation and ICU admission

Commonly used; limited supporting data Unclear derivation of beneficial effects

– Venodilation – Afterload reduction– Respiratory relaxation

Evidence suggesting association with adverse outcomes 1,2

– ↑ need for intubation and ICU admission

1 Hoffman et al. Chest 1987;92:586-93.2 Sacchetti et al. Am J Emerg Med 1999;17:571-4.

Non-invasive VentilationNon-invasive Ventilation

Consider if poor response at 30 min– CPAP: continuous positive airway pressure 1,2

Reduction in need for ETI by 26 % Trend towards ↑ survival

– BiPAP: bilevel positive airway pressure 3,4,5

↓ time to symptom resolution (30 vs. 105 min) ↓ intubation rate (~ 23 %)

One prospective comparison trial 6 – ↑ MI rate with BiPAP

Consider if poor response at 30 min– CPAP: continuous positive airway pressure 1,2

Reduction in need for ETI by 26 % Trend towards ↑ survival

– BiPAP: bilevel positive airway pressure 3,4,5

↓ time to symptom resolution (30 vs. 105 min) ↓ intubation rate (~ 23 %)

One prospective comparison trial 6 – ↑ MI rate with BiPAP

1 Berstein et al. NEJM 1991;325:1825-30.2 Pang et al. Chest 1998;114:1185-92.3 Masip et al. Lancet 2000;356:2126-32.4 Levitt MA. J Emerg Med 2001;21:363-9.5 Nava et al. Am J Resp Crit Care Med 2003;168:1432-7.6 Mehta et al. Crit Care Med 1997;620-8.

EBM Literature Classification Schema

EBM Literature Classification Schema

Design/Class

Therapy

Diagnosis

Prognosis

I

Randomized, controlled trial or meta-analyses of randomized trials

Prospective cohort using a criterion standard

Population prospective cohort

II

Nonrandomized trial

Retrospective observational

Retrospective cohort Case control

III

Case series Case report Other (eg, consensus, review)



EBM Recommendation LevelsEBM Recommendation Levels Level A

– Generally accepted principles for Pt management that reflect a high degree of clinical certainty (i.e., based on Class I or overwhelming, directly pertinent Class II evidence )

Level B

– Recommendations for Pt management that may identify a particular strategy of range of strategies that reflect moderate clinical certainty (i.e., based on directly pertinent Class II evidence, directly pertinent decision analysis, or strong Class III consensus)

Level C

– Other strategies for patient management that are based on preliminary evidence, or in the absence of any published

literature, based on panel consensus

Level A

– Generally accepted principles for Pt management that reflect a high degree of clinical certainty (i.e., based on Class I or overwhelming, directly pertinent Class II evidence )

Level B

– Recommendations for Pt management that may identify a particular strategy of range of strategies that reflect moderate clinical certainty (i.e., based on directly pertinent Class II evidence, directly pertinent decision analysis, or strong Class III consensus)

Level C

– Other strategies for patient management that are based on preliminary evidence, or in the absence of any published

literature, based on panel consensus

ACEP Clinical Guideline Questions

ACEP Clinical Guideline Questions

1. Does a B-type natriuretic polypeptide (BNP) or NT-ProBNP measurement improve the diagnostic accuracy over standard clinical judgment in the assessment of possible acute heart failure syndromes in the ED?

2. Is there a role for noninvasive positive-pressure ventilatory support in the ED management of patients with acute heart failure syndromes and respiratory distress?

3. Should vasodilator therapy (eg, nitrates, nesiritide, and ACE inhibitors) be prescribed in the ED management of patients with acute heart failure syndromes?

4. Should diuretic therapy be prescribed in the ED management of patients with acute heart failure syndromes?

1. Does a B-type natriuretic polypeptide (BNP) or NT-ProBNP measurement improve the diagnostic accuracy over standard clinical judgment in the assessment of possible acute heart failure syndromes in the ED?

2. Is there a role for noninvasive positive-pressure ventilatory support in the ED management of patients with acute heart failure syndromes and respiratory distress?

3. Should vasodilator therapy (eg, nitrates, nesiritide, and ACE inhibitors) be prescribed in the ED management of patients with acute heart failure syndromes?

4. Should diuretic therapy be prescribed in the ED management of patients with acute heart failure syndromes?

Patient Management Recommendations

Question 1


Question 1 Level A recommendations. None specified.

Level B recommendations. The addition of a single BNP or NT-proBNP measurement can improve the diagnostic accuracy compared to standard clinical judgment alone in the diagnosis of acute heart failure syndrome among patients presenting to the ED with acute dyspnea. Use the following guidelines:

– BNP <100 pg/dL or NT-proBNP <300 pg/dL failure syndrome unlikely (Approximate LR -0.1)

– BNP >500 mg/dL or NT-proBNP >1,000 pg/dL heart failure syndrome likely (Approximate LR +6)

Level C recommendations. None specified.

Level A recommendations. None specified.

Level B recommendations. The addition of a single BNP or NT-proBNP measurement can improve the diagnostic accuracy compared to standard clinical judgment alone in the diagnosis of acute heart failure syndrome among patients presenting to the ED with acute dyspnea. Use the following guidelines:

– BNP <100 pg/dL or NT-proBNP <300 pg/dL failure syndrome unlikely (Approximate LR -0.1)

– BNP >500 mg/dL or NT-proBNP >1,000 pg/dL heart failure syndrome likely (Approximate LR +6)

Level C recommendations. None specified.


Question 2



Level B recommendations. Use 5 to 10 mm Hg CPAP by nasal or face mask as therapy for dyspneic patients with acute heart failure syndrome without hypotension or the need for emergent intubation to improve heart rate, respiratory rate, blood pressure, and reduce the need for intubation, and possibly reduce inhospital mortality.

Level C recommendations. Consider using BiPAP as an alternative to CPAP for dyspneic patients with acute heart failure syndrome; however, data about the possible association between BiPAP and myocardial infarction remain unclear.


Level B recommendations. Use 5 to 10 mm Hg CPAP by nasal or face mask as therapy for dyspneic patients with acute heart failure syndrome without hypotension or the need for emergent intubation to improve heart rate, respiratory rate, blood pressure, and reduce the need for intubation, and possibly reduce inhospital mortality.

Level C recommendations. Consider using BiPAP as an alternative to CPAP for dyspneic patients with acute heart failure syndrome; however, data about the possible association between BiPAP and myocardial infarction remain unclear.


Question 3



Level B recommendations. Administer intravenous nitrate therapy to patients with acute heart failure syndromes and associated dyspnea.

Level C recommendations. – 1. Because of the lack of clear superiority of nesiritide over nitrates in acute heart failure syndrome and the current uncertainty regarding its safety, nesiritide generally should not be considered first line therapy for acute heart failure syndromes.

– 2. Angiotensin-converting enzyme (ACE) inhibitors may be used in the initial management of acute heart failure syndromes, although patients must be monitored for first dose hypotension.


Level B recommendations. Administer intravenous nitrate therapy to patients with acute heart failure syndromes and associated dyspnea.

Level C recommendations. – 1. Because of the lack of clear superiority of nesiritide over nitrates in acute heart failure syndrome and the current uncertainty regarding its safety, nesiritide generally should not be considered first line therapy for acute heart failure syndromes.

– 2. Angiotensin-converting enzyme (ACE) inhibitors may be used in the initial management of acute heart failure syndromes, although patients must be monitored for first dose hypotension.


Question 4



Level B recommendations. Treat patients with moderate-to-severe pulmonary edema resulting from acute heart failure with furosemide in combination with nitrate therapy.

Level C recommendations. 1. Aggressive diuretic monotherapy is unlikely to prevent the need for endotracheal intubation compared with aggressive nitrate monotherapy.

2. Diuretics should be administered judiciously, given the potential association between diuretics, worsening renal function, and the known association between worsening renal function at index hospitalization and long-term mortality.


Level B recommendations. Treat patients with moderate-to-severe pulmonary edema resulting from acute heart failure with furosemide in combination with nitrate therapy.

Level C recommendations. 1. Aggressive diuretic monotherapy is unlikely to prevent the need for endotracheal intubation compared with aggressive nitrate monotherapy.

2. Diuretics should be administered judiciously, given the potential association between diuretics, worsening renal function, and the known association between worsening renal function at index hospitalization and long-term mortality.

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ACEP Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting...

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