Presentation on theme: "PGY-1, Emergency Medicine"— Presentation transcript:
1PGY-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 SyndromesBrian McMichael, M.D.PGY-1, Emergency MedicineWayne State University/Detroit Medical Center (Detroit Receiving Hospital)
2ObjectivesGive 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 PolicyConsider rational interventional approaches that take into account evidence and the particularities of patient history and physical upon presentation.
3GoalsParticipants will be able to understand the four core questions of the ACEP Clinical PolicyParticipants will be able to understand the best supported conclusions to the four core questionsParticipants will be able to formulate treatment approaches likely to be most effective for a given history and physical of patient scenarios.
4Perspective Prevalence: 5,000,000 Incidence: 550,000 ~ 2 % of total US populationIncidence: 550,000Approaches 10 per 1000 for those > 65 yrsAmerican Heart Association. Heart Disease and Stroke Statistics Update.
5Prevalence by Age and Gender American Heart Association. Heart Disease and Stroke Statistics Update.
6Perspective: Hospital Care Total hospital discharges in 2001: 995,000164 % increase from 1979Most common DRG among pts > 65American Heart Association. Heart Disease and Stroke Statistics Update.
7Who is at Risk for Heart Failure Development? 1,2 Overall, lifetime risk is 1 in 5 for those > 40 yrsHTN and CAD are primary risk factorsRisk ↓ to 1 in 9 for males and 1 in 6 for females without hx of CADHTN antedates disease onset in 75%Chronic BP ≥ 160/100: risk ~ 1 in 4Chronic BP < 140/90: risk ~ 1 in 81 Lloyd-Jones DM, et al. Circulation. 2002;106:2 Levy D, et al. JAMA 1996;275(20):
8Disproportionate Risk for African-Americans 1-5 50-75% excess rate of new-onset HFYounger age with more advanced disease at initial presentationMore rapid progression from asymptomatic to symptomatic phase1 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.
9Disproportionate Risk May be explained by divergence in etiology 1-3Hypertensive cardiomyopathy in AAIschemic cardiomyopathy in Caucasians1 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):
10DMC Statistics Total ED visits for HF 1999-2004 Site 1999 2000 2001 200220032004ALL YEARSDRH1,0441,0551,2431,1511,1251,1176,735HARPER7127847267977867944,599HVSH3654334534944904462,681SGH1,5891,6091,5041,4391,3751,4758,991TOTAL3,7103,8813,9263,7763,83223,006
11Perspective: Bottom Line 142.557.963.529.620406080100120140160Coronary Heart DiseaseStrokeHypertensive DiseaseHeart FailureBillions of DollarsAmerican Heart Association. Heart Disease and Stroke Statistics Update.
12What is Heart Failure ?Syndrome defined by inadequate cardiac performancePrimarily a reflection of ventricular dysfunctionDiminished inotropy (systolic ~ 55 %)Diminished compliance (diastolic ~ 45 %)Exacerbated by changes in volume status
18More on Etiology of Cardiac Dysfunction SystolicMales 50-70Impaired contractilityChamber dilatedEccentric hypertrophyCardiomegaly notedIschemic in natureAudible S3Limited ability to differentiate based solely on clinical parameters 1DiastolicElderly femalesImpaired complianceChamber narrowedConcentric hypertrophyCardiomegaly absentHypertensive in natureAudible S41 Thomas et al. Am J Med 2002;112:
19General Principles Focus is on clinical presentation not etiology 1,2 Common denominator = ↑ LVEDPEnd result = congestionBalance specificity with sensitivityRule-out vs. rule-in approach1 Gheorghiade et al. Circulation 2005;112:2 Friedewald et al. Am J Cardiol 2007;10:19
20Basic Pathophysiology Cardiac dysfunction leads to diminished output with arterial underfillingBaroreceptor activationCarotid sinusLeft ventricleAortic arch↓ glomerular filtration rateTriggers compensatory response
21Basic Pathophysiology From: Schrier and Abraham. NEJM 1999;341:583.
22Compensatory Response Enhanced sympathetic tonePredominantly norepinephrine 1,2Improves circulatory integrity↑ inotropy and chronotropy (β1)↑ preload and afterload (α1)↑ effective volume (α1)Beneficial effects ↓ over timeReceptor down-regulation and G-protein uncouplingInduction of myocyte toxicity 3,41 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:
24Compensatory Response Stimulation of neurohormonal modulatorsRenin-angiotensin-aldosterone system (RAAS)ANPArginine vasopressinCytokine release
25RAAS Angiotensinogen Renin Angiotensin I Bradykinin Chymase, other proteasesACE (Lung, etc)Inactive kininsAngiotensin IIProteaseActive angiotensin fragments: Ang III, Ang IV, Ang 1-7Direct effects of AT II
26Angiotensin-II Vasoconstriction Promotion of sodium reabsorption Efferent > afferent arteriolar constrictionResults in ↑ GFRPromotion of sodium reabsorptionDirect effect on proximal tubuleIndirect through stimulation of aldosterone releaseDipsogenic responseCardiac (and vascular) remodeling
27Aldosterone Sodium (and water) reabsorption at collecting ducts Typical effect on extracellular volume ~ 2 LRegulated by intrinsic feedback 1Based on distal sodium deliveryAltered in heart failure; results in sodium and fluid retentionDiminishes arterial complianceStimulates myocyte collagen synthesis 21 Schrier et al. NEJM 1999;341:2 Cohn et al. J Am Coll Cardiol 2000;35:
28Arginine Vasopressin Vasoconstriction (V1A receptor) Antidiuresis (V2 receptor)Occurs in collecting ductsInduces synthesis and translocation of aquaporin-2 water channelsSuppressed by atrial stretch receptorsImpaired in heart failure, with free-water retentionNielsen et al. Proc Natl Acad Sci USA 1995;92:
29Cytokine Mediators 1,2 Proinflammatory Vasoactive Triggered by myocardial inflammation? role of endotoxin from hypoperfused intestinesTumor necrosis factor (TNF-α)Transforming growth factor β (TGF- β)Interleukins (IL-1,2 and 6)Intracellular adhesion molecules (ICAM)VasoactiveEndothelin (ET)1 Anker et al. Heart 2004;90:2 Aukurst et al. Autoimmunity Reviews 2004;3:221-7.
30Endothelin: Receptors & Effects ETA (upregulated)Vasoconstriction (pulmonary HTN)Smooth muscle and myocyte hypertrophy↑ inotropy and chronotropy↑ sodium and water retentionETB (downregulated)Vasodilation↑ aldosterone production↑ ET-1 clearance and autocrine regulationSpieker et al. J Am Coll Cardiol 2001;37:
31Ventricular Remodeling Gradual response to initial insult, circulating factors and oxidative stressCycle leading to progressive dysfunctionInsult with myocyte necrosisMyocyte apoptosisHypertrophy of remaining cellsCollagen degradation with progressive fibrosisFibroblast proliferation with collagen synthesisCohn et al. J Am Coll Cardiol 2000;35:
32Ventricular Remodeling: Translational Model Hunter and Chien. NEJM 1999;341:
33Infarct Related Remodeling Myocyte elongationFrom: Jessup et al. N Engl J Med 2003;348:
34Ischemic Remodeling Wall thinning may cause chordae retraction Result = ischemic mitral valve requrgitationBursi et al. Am J Med 2006;119:
35Non-infarct Related Remodeling “Concentric” Hypertrophy“Eccentric” HypertrophyFrom: Jessup et al. N Engl J Med 2003;348:
36Counter Regulation Stimulation of natriuretic peptide system A-type or atrial (ANP) and B-type or brain (BNP) most importantProduce diuresis, natriuresis and vasodilationRelease of coenzyme Q10Enhances mitochondrial function
38Counter Regulation Release of endogenous vasodilators Prostacyclin and prostaglandin EBradykininNitric oxide (NO)Produced from L-arginine by NO synthetaseSoluble or bound form (endothelial cells)Induces smooth muscle relaxation via cGMPTenuous balance
43CardioRenal Syndrome Heart failure plus Often complicated by anemia Chronic renal insufficiencyWorsening renal function during treatment25% or > increase in Cr or BUNDifficult diuresis w/o worsening renal functionACE (-) intolerance from hypotension or hyperkalemiaOften complicated by anemia
44Diagnosis of Heart Failure Can be difficult on clinical basis aloneLimited sensitivity of physical examination 1,2Electrocardiogram often not helpful 3,4Common chest x-ray findings unreliable and often non-predictive 5CepahalizationCardiomegalyInterstitial edema1 Stevenson et al. JAMA 1989;261:884-82 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:
45Diagnosis of Heart Failure Difficult based on common variablesLimited sensitivity of physical examination 1,2Electrocardiogram often not helpful 3,4Atrial fibrillation may be found in up to 1/3Interventricular conduction delays in 1/4Common chest x-ray findings unreliable and often non-predictive 5,6Normal in ~ 20%↑ reliance on serum markers1 Stevenson et al. JAMA 1989;261:884-82 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
46Criterion Diagnosis of Heart Failure FraminghamMost commonly usedDefines cases as questionable, probable or definite HFDefinite requires 2 major or 1 major and 2 minor criteriaNational Health and Nutrition Examination Surveys (NHANES)BostonEuropean Society of Cardiology46
47Framingham Criteria 1,2 Major Criteria Minor Criteria Clinical PND Orthopnea↑ JVPHepatojugular refluxRalesS3 gallopChest x-rayCardiomegalyPulmonary edemaMinor CriteriaAnkle edemaNight coughDyspnea on exertionHepatomegalyPleural effusionHR ≥ 120Wt loss ≥ 4.5 kg in 5 d Considered major criterion when occurring in response to diuretics1 McKee et al. NEJM 1971;285:2 Kannel et al. Arch Intern Med 1999;159:47
48Clinical Diagnostic Accuracy Wang et al. JAMA 2005;294:48
49Exam Findings Do Matter Drazneret al. NEJM 2001;345:49
51Gallop Murmur Mnemonics MontrealSLOSH'-ing-in SLOSH'-ing-in SLOSH'-ing-inS S2 S S S2 S3 S S2 S3Kentucky/Tennessee?(you decide)S4Torontoa-STIFF'-wall a-STIFF'-wall a-STIFF'-wallS4 S S S4 S S S4 S S2Kentucky/Tennessee?(you decide)
52Acoustic Cardiography: Test Characteristics Marcus et al. JAMA 2005;295:52
53Ear of the Beholder?Marcus et al. Arch Intern Med 2006;166:53
56BNP Robust independent predictive value Level > 100 pg/ml more accurate than clinical criteria for diagnosisBNP: 83 %Framingham: 73 %NHANES: 67 %VariableOdds RatioBNP > 100 pg/ml29.6Hx of CHF11Cephalization on CXR10.7Peripheral edema2.88Audible rales2.24↑ JVP1.87Maisel et al. NEJM 2002;347:161-7.56
58BNP: Pooled Operating Characteristics Wang et al. JAMA 2005;294:58
59Should You Obtain a BNP for High Probability Pts ? Correlates with disease severity and provides prognostic information 1,2BNP > 480 pg/ml51 % with HF event at 6 mosRate only 2.5 % when < 230 pg/mlBNP > 700 pg/mlHR (death or admit) = 15.2Enables serial comparison 3Inc. risk of death when remains “high”≥ 97 pg/ml1 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
60BNP: Using Your Results Utilization improves clinical judgment 1Degree dependent on pre-test probabilityEffect greatest for “intermediate” ptsBest use: acute dyspneaReliably differentiates HF from lung disease 2Can reduce admissions, ICU use and LOS 31 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
61BNP: Things to Consider May be lower than expected withFlash pulmonary edemaDiastolic dysfunctionMild elevation ( pg/ml) found with other conditionsCor PulmonalePECOPDPulmonary HTN61
62Other Natriuretic Peptides ANP and N-ANPCorrelates with ↓ LVEF, but lower sensitivity and NPV than BNP 1NT-proBNPSimilar overall accuracy to BNPMay be better predictor of LV dysfunction 2,3Wall motion index < 1.2or LVEF < 40 %Useful as a marker of therapeutic effectiveness 41 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
64Natriuretic Peptide Caveats Relative increase in womenInverse relationship with BMIKrauser et al. Am Heart J 2005;64
65Natriuretic Peptide Caveats Daniels et al. Am Heart J 2006;151:65
66Natriuretic Peptide Caveats Higher with renal dysfunctionOptimal cut-point =1200 pg/mlOptimal cut-point =200 pg/mlMcCollough et al. Am J Kidney Dis 2003;41:571-9.Anwaruddin et al. JACC 2006;47:91-7.66
67Echocardiography Gold standard Functional and structural information Ejection fractionWall motionTissue doppler and harmonicsChamber sizeLV wall thickness and massRegurgitant mitral valve diameterUtility in acute setting is unclear67
68Echocardiography Provides long-term prognostic information Annual mortality with EF ≤ 10 %: ~ 29 % !Enables diagnosis of HF etiology 1Systolic dysfunction: EF < 50 %Diastolic dysfunction: EF ≥ 50 % with impaired relaxation and elevation of filling pressuresDoppler tissue imaging at mitral annulus1 Bursi et al. JAMA 2006;296:68
70Diuretics Limited evidence, but used empirically Loop agents most commonInitial diuresis at 30 min 1Peak effect at 2-4 hrsMaximal with mg furosemideAvg in-hospital net diuresis > 4 L 2Vasodilatory effect at 15 min 3Latent constriction through RAAS and adrenergic activation 4↑ efficacy in combination with thiazides1 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.
71Nitrates Recognized benefit since mid-1970’s Produces rapid ↓ in PCWP with clinical improvement 1At lower doses, preload reduction through venodilation 2Arterial dilation with afterload reduction at higher IV doses (≥ 250 mcg/min) 2,3Dose-effect relationshipMore pronounced with ↑ resistance 41 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.
72Nitroprusside Effective in refractory ACPE with ↑ SVR Enables concurrent venous and arterial dilationRequires arterial line placement for proper titrationProduces reflex tachycardiaPotential for cyanide toxicityMinimized by use of thiosulfateGuiha et al. NEJM 1974;291:
73Nesiritide Exogenous BNP Rapid onset Elimination half-life = 18 min Peak effect in minElimination half-life = 18 minDosing2 mcg/kg bolusInfusion at 0.01 mcg/kg/min (titration to a max of 0.03 mcg/kg/min)Safe with dose dependent ↓ in PCWPColucci et al. NEJM 2000;343:
74ACE Inhibitors Limited data on use in acute setting Sublingual captopril (25 mg) 1,2Diminished rate of intubation (9 vs 20 %)Improved dyspnea scores at 30 minEarly improvements in SVI and CIIV enalaprilat 3Improved hemodynamics with 1 mg infusionNo data on bolus dosing1 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:
75Inotropic Agents Usually reserved for those with ↓ CO Dobutamine 1,2 Increases ventricular ectopy and myocardial oxygen demandMilrinone 3,4Prolonged LOS and ↑ 60-day mortalityMore pronounced with ischemic etiology↑ in-hospital mortality for both versus NTG and nesiritide 51 Leier et al. Circulation 1977;56:2 Burger et al. Am J Cardiol 2001;88:35-39.3 Cuffe et al. JAMA 2002;287:1541-74 Felker et al. J Am Coll Cardiol 2003;41:5 Abraham et al. J Card Fail 2003; 9:S81.
76Inotropic Agents Levosimendan Novel calcium sensitizer Contractility improvement w/o ↑ O2 consumptionOpens K-ATP channelDose-response relationship with ↑ in CO/SV and ↓ in PCWP 1,2Dosing: IV bolus (6 to 24 mcg/kg) followed by infusion (0.05 to 0.2 mcg/kg/min)Trial data promising1 Nieminen et al. J Am Coll Cardiol. 2000;36: Slawsky et al. Circulation 2000;102:
77Morphine Sulfate Commonly used; limited supporting data Unclear derivation of beneficial effectsVenodilationAfterload reductionRespiratory relaxationEvidence suggesting association with adverse outcomes 1,2↑ need for intubation and ICU admission1 Hoffman et al. Chest 1987;92:2 Sacchetti et al. Am J Emerg Med 1999;17:571-4.
78Non-invasive Ventilation Consider if poor response at 30 minCPAP: continuous positive airway pressure 1,2Reduction in need for ETI by 26 %Trend towards ↑ survivalBiPAP: 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 BiPAP1 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.
80EBM Recommendation Levels Level AGenerally 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 BRecommendations 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 COther strategies for patient management that are based on preliminary evidence, or in the absence of any published literature, based on panel consensus
81ACEP 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?
82Patient 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.
83Patient 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.
84Patient 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.
85Patient 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.