1. PGY-1, Emergency Medicine
ACEP Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department with Acute Heart Failure Syndromes
Brian McMichael, M.D.
PGY-1, Emergency Medicine
Wayne State University/Detroit Medical Center (Detroit Receiving Hospital)

2. Objectives
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.

3. Goals
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.

4. Perspective Prevalence: 5,000,000 Incidence: 550,000
~ 2 % of total US population
Incidence: 550,000
Approaches 10 per 1000 for those > 65 yrs
American Heart Association. Heart Disease and Stroke Statistics Update.

5. Prevalence by Age and Gender
American Heart Association. Heart Disease and Stroke Statistics Update.

6. Perspective: Hospital Care
Total hospital discharges in 2001: 995,000
164 % increase from 1979
Most common DRG among pts > 65
American Heart Association. Heart Disease and Stroke Statistics Update.

7. 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
1 Lloyd-Jones DM, et al. Circulation. 2002;106:
2 Levy D, et al. JAMA 1996;275(20):

8. 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
1 McCullough PA, et al. J Am Coll Cardiol 2002;39(1):60-9.
2 Yancy CW. Curr Cardiol Rep 2002;4(3):
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.

9. Disproportionate Risk
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):
3 Mathew J, et al. Am J Cardiol 1996;78(12):

10. DMC Statistics Total ED visits for HF 1999-2004 Site 1999 2000 2001
2002
2003
2004
ALL 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
3,776
3,832
23,006

11. Perspective: Bottom Line
142.5
57.9
63.5
29.6 20 40 60 80
100
120
140
160
Coronary Heart Disease
Stroke
Hypertensive Disease
Heart Failure
Billions of Dollars
American Heart Association. Heart Disease and Stroke Statistics Update.

12. 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

13. Starling Curve Stroke Volume LV End-Diastolic Volume (or Pressure)
Normal response
Stroke
Volume
Baseline
Heart failure
LV End-Diastolic Volume (or Pressure)

14. Normal Pressure-Volume Loop
Inotropy
4. AV Closes
3. AV Opens LV
Pressure
Compliance SV
1. MV Opens
2. MV Closes
LV Volume

15. Normal Pressure-Volume Loop
Inotropy LV
Pressure
Compliance SV
EDP
ESV
EDV
LV Volume

16. Systolic Dysfunction LV
Pressure
LV Volume

17. Diastolic DysfunctionLV
Pressure
LV Volume

18. 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
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:

19. General 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
1 Gheorghiade et al. Circulation 2005;112:
2 Friedewald et al. Am J Cardiol 2007;10: 19

20. Basic Pathophysiology
Cardiac dysfunction leads to diminished output with arterial underfilling
Baroreceptor activation
Carotid sinus
Left ventricle
Aortic arch
↓ glomerular filtration rate
Triggers compensatory response

21. Basic Pathophysiology
From: Schrier and Abraham. NEJM 1999;341:583.

22. Compensatory 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
1 Braunwald et al. Proc R Soc Med 1965;58:
2 Francis et al. Ann Intern Med 1984;101:370-7.
3 Schrier et al. NEJM 1999;341:
4 Mann et al. Circulation 1992;85:

23. Biochemical Response to Adrenergic Stimulation

24. Compensatory Response
Stimulation of neurohormonal modulators
Renin-angiotensin-aldosterone system (RAAS)
ANP
Arginine vasopressin
Cytokine release

25. RAAS Angiotensinogen Renin Angiotensin I Bradykinin
Chymase, other proteases
ACE (Lung, etc)
Inactive kinins
Angiotensin II
Protease
Active angiotensin fragments: Ang III, Ang IV, Ang 1-7
Direct effects of AT II

26. Angiotensin-II Vasoconstriction Promotion of sodium reabsorption
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

27. Aldosterone 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:
2 Cohn et al. J Am Coll Cardiol 2000;35:

28. Arginine 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
Nielsen et al. Proc Natl Acad Sci USA 1995;92:

29. Cytokine Mediators 1,2 Proinflammatory Vasoactive
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:
2 Aukurst et al. Autoimmunity Reviews 2004;3:221-7.

30. 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
Spieker et al. J Am Coll Cardiol 2001;37:

31. Ventricular Remodeling
Gradual response to initial insult, circulating factors and oxidative stress
Cycle leading to progressive dysfunction
Insult with myocyte necrosis
Myocyte apoptosis
Hypertrophy of remaining cells
Collagen degradation with progressive fibrosis
Fibroblast proliferation with collagen synthesis
Cohn et al. J Am Coll Cardiol 2000;35:

32. Ventricular Remodeling: Translational Model
Hunter and Chien. NEJM 1999;341:

33. Infarct Related Remodeling
Myocyte elongation
From: Jessup et al. N Engl J Med 2003;348:

34. Ischemic Remodeling Wall thinning may cause chordae retraction
Result = ischemic mitral valve requrgitation
Bursi et al. Am J Med 2006;119:

35. Non-infarct Related Remodeling
“Concentric” Hypertrophy
“Eccentric” Hypertrophy
From: Jessup et al. N Engl J Med 2003;348:

36. Counter 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

37. CHF and Na+ Retention

38. Counter 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

39. Nitric Oxide Balance
Hare, JM. NEJM 2004;351:

40. 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
1 Schonberger and Seidman. Am J Hum Genet 2001;69:
2 Olson et al. JAMA 2005;293:
3 Bienengraeber et al. Nat Genet 2004;36:
4 Schmitt et al. Science 2003;299:
5 Wehrens et al. Science 2004;304:292-6.

41. Calcium Cycle Modulation
Renlund, DG. N Engl J Med 2004;351:

42. Heart Failure Presentations
Fatigue
Right-sided features
Peripheral edema
Ascites
Left-sided features
Dyspnea (exertional or nocturnal)
Rales
Acute cardiogenic pulmonary edema (ACPE)

43. CardioRenal Syndrome Heart failure plus Often complicated by anemia
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

44. Diagnosis 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
1 Stevenson et al. JAMA 1989;261:884-8
2 Badgett et al. JAMA 1997;277:
3 Davie et al. BMJ 1996;312:222.
4 Gillespie et al. BMJ 1997;314:
5 Badgett et al. J Gen Intern Med 1996;11:

45. Diagnosis of Heart Failure
Difficult based on common variables
Limited sensitivity of physical examination 1,2
Electrocardiogram often not helpful 3,4
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
1 Stevenson et al. JAMA 1989;261:884-8
2 Badgett et al. JAMA 1997;277:
3Davie et al. BMJ 1996;312:222.
4 Gillespie et al. BMJ 1997;314:
5 Badgettet al. J Gen Intern Med 1996;11:
6 Collins et al. Ann Emerg Med 2006;47;13-8. 45

46. Criterion 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 46

47. Framingham Criteria 1,2 Major Criteria Minor Criteria Clinical PND
Orthopnea
↑ JVP
Hepatojugular reflux
Rales
S3 gallop
Chest x-ray
Cardiomegaly
Pulmonary edema
Minor Criteria
Ankle edema
Night cough
Dyspnea on exertion
Hepatomegaly
Pleural effusion
HR ≥ 120
Wt loss ≥ 4.5 kg in 5 d Considered major criterion when occurring in response to diuretics
1 McKee et al. NEJM 1971;285:
2 Kannel et al. Arch Intern Med 1999;159: 47

48. Clinical Diagnostic Accuracy
Wang et al. JAMA 2005;294: 48

49. Exam Findings Do Matter
Drazneret al. NEJM 2001;345: 49

50. Acoustic Cardiography 50

51. Gallop Murmur Mnemonics
Montreal
SLOSH'-ing-in    SLOSH'-ing-in SLOSH'-ing-in
S S2 S S S2 S3 S S2 S3
Kentucky/Tennessee?
(you decide) S4
Toronto
a-STIFF'-wall     a-STIFF'-wall    a-STIFF'-wall
S4 S S S4 S S S4 S S2
Kentucky/Tennessee?
(you decide)

52. Acoustic Cardiography: Test Characteristics
Marcus et al. JAMA 2005;295: 52

53. Ear of the Beholder?
Marcus et al. Arch Intern Med 2006;166: 53

54. CXR and ECG
Wang et al. JAMA 2005;294: 54

55. Serum Markers Natriureticpeptides Norepinephrine Endothelin
ANP
N-ANP
BNP
NT-proBNP
Norepinephrine
Endothelin
Proinflammatorycytokines
TNF-α, IL-1β, IL-6 55

56. BNP Robust independent predictive value
Level > 100 pg/ml more accurate than clinical criteria for diagnosis
BNP: 83 %
Framingham: 73 %
NHANES: 67 %
Variable
Odds Ratio
BNP > 100 pg/ml
29.6
Hx of CHF 11
Cephalization on CXR
10.7
Peripheral edema
2.88
Audible rales
2.24
↑ JVP
1.87
Maisel et al. NEJM 2002;347:161-7. 56

57. ROC Curve (BNP) @ 100 pg/ml cut off: Sens 90 % Spec 76 PPV 79 NPV 89
Maiselet al. NEJM 2002;347:161-7. 57

58. BNP: Pooled Operating Characteristics
Wang et al. JAMA 2005;294: 58

59. 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
1 Harrison et al. Ann Emerg Med 2002;39:
2 Logeart et al. J Am Coll Cardiol 2004;43:
3 Latini et al. Am J Med 2006;119:70.e23-30. 59

60. 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
1 McCollough et al. Circulation 2002;106:
2 Morrison et al. J Am Coll Cardiol 2002;39:202-9.
3 Mueller et al. NEJM 2004;350: 60

61. BNP: Things to Consider
May be lower than expected with
Flash pulmonary edema
Diastolic dysfunction
Mild elevation ( pg/ml) found with other conditions
Cor Pulmonale PE
COPD
Pulmonary HTN 61

62. Other 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
1 Collins et al. Ann Emerg Med 2003;41:
2 Talwar et al. Eur Heart J 1999;20:
3 Hammerer-Lecher et al. Clin Chim Acta 2001;310:193-7.
4 Troughton et al. Lancet 2000;355: 62

63. NT-proBNP
Moe et al. Circulation 2007;115:

64. Natriuretic Peptide Caveats
Relative increase in women
Inverse relationship with BMI
Krauser et al. Am Heart J 2005; 64

65. Natriuretic Peptide Caveats
Daniels et al. Am Heart J 2006;151: 65

66. Natriuretic Peptide Caveats
Higher with renal dysfunction
Optimal cut-point =
1200 pg/ml
Optimal cut-point =
200 pg/ml
McCollough et al. Am J Kidney Dis 2003;41:571-9.
Anwaruddin et al. JACC 2006;47:91-7. 66

67. Echocardiography 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 67

68. Echocardiography 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: 68

69. CHF Treatment Modalities

70. Diuretics Limited evidence, but used empirically
Loop agents most common
Initial diuresis at 30 min 1
Peak effect at 2-4 hrs
Maximal with 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
1 Brater DC. NEJM 1998; 339:
2 Steimle et al. Circulation 1997;96:
3 Dikshit et al. NEJM 1973;288:
4 Francis et al. Ann Intern Med 1985;103:1-6.

71. Nitrates 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:
2 Imhof et al. Eur J Clin Pharmacol 1980;18:
3 Herling IM. Am Heart J 1984;108:141-9.
4 Haber et al. J Am Coll Cardiol 1993;22:251-7.

72. Nitroprusside 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:

73. Nesiritide Exogenous BNP Rapid onset Elimination half-life = 18 min
Peak effect in 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:

74. ACE 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
1 Haude et al. Int J Cadiol 1990;27:351-9.
2 Hamilton et al. Acad Emerg Med 1996;3:
3 Annane et al. Cirulation 1996;94:

75. Inotropic 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
1 Leier et al. Circulation 1977;56:
2 Burger et al. Am J Cardiol 2001;88:35-39.
3 Cuffe et al. JAMA 2002;287:1541-7
4 Felker et al. J Am Coll Cardiol 2003;41:
5 Abraham et al. J Card Fail 2003; 9:S81.

76. Inotropic 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
1 Nieminen et al. J Am Coll Cardiol. 2000;36: Slawsky et al. Circulation 2000;102:

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

78. Non-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
1 Berstein et al. NEJM 1991;325:
2 Pang et al. Chest 1998;114:
3 Masip et al. Lancet 2000;356:
4 Levitt MA. J Emerg Med 2001;21:363-9.
5 Nava et al. Am J Resp Crit Care Med 2003;168:
6 Mehta et al. Crit Care Med 1997;620-8.

79. EBM Literature Classification Schema

80. EBM 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

81. ACEP Clinical Guideline Questions
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?
Is there a role for noninvasive positive-pressure ventilatory support in the ED management of patients with acute heart failure syndromes and respiratory distress?
Should vasodilator therapy (eg, nitrates, nesiritide, and ACE inhibitors) be prescribed in the ED management of patients with acute heart failure syndromes?
Should diuretic therapy be prescribed in the ED management of patients with acute heart failure syndromes?

82. Patient Management Recommendations 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.

83. Patient Management Recommendations Question 2
Level A recommendations. None specified.
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.

84. Patient Management Recommendations Question 3
Level A recommendations. None specified.
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.

85. Patient Management Recommendations Question 4
Level A recommendations. None specified.
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.

86. Comments and Questions ?