1. Strategies for Diagnosis, Risk Stratification and Treatment of the Acutely Decompensated Heart Failure Patient John H. Burton, MD Residency Program Director Dept. Emergency Medicine Albany Medical Center

2. burtonj@ mail.amc.edu

3. Heart Failure n Approximately 5 million Americans have CHF (male to female ratio 1:1) n Incidence of 10/1000 > 65 years of age n 550,000 new cases/year n Hospital discharges 1,000,000 (2001) n Single largest expense for Medicare n Five-year mortality rate as high as 50% AHA. 2001 Heart and Stroke Statistical Update

4. Heart Failure Hospitalizations AHA, 1998 Heart and Statistical Update NCHS, National Center for Health Statistics The number of heart failure hospitalizations is increasing in both men and women CDC/NCHS: Hospital discharges include patients both living and dead. AHA Heart and Stroke Statistical Update 2001

5. Hospital Visits for Congestive Heart Failure Initial Episode 21% Repeat Visit 79% Rates of Hospital Readmission 2% within 2 days 20% within 1 month 50% within 6 months Approximately 85% of the ED visits for CHF result in hospitalizations Cardiology Roundtable 1998

6. A brief discussion of the works of this thing...

7. The Pump: 1. A Mechanical Component 2. An Electrical Component

8. 1. A Mechanical Component 2. An Electrical Component 65%

10. PUMPS LESS!!!

11. FILLS LESS!!!

12. Filling….Pumping Problems with Filling... Problems with Pumping...

13. Pumping Just how little pumping can one get away with? Normal - 65% No Symptoms - 40-65% Lethargy, less exercise tolerance - 30-45% Shortness of breath - 20 - 30% Incompatible with life - <15%

14. Etiology of Acute Heart Failure n Hypertension n Ischemia n Sustained Arrhythmias n Cardiomyopathy o EtOH, infiltrative n Valvular Heart Disease n Pericardial Disease Approximately 1/4th Diastolic Dysfxn

15. AFTERloadPREloadContractility

16. PREload

17. AFTERload

18. Contractility

19. DEFINITION CHF E. Braunwald “The situation when the heart is incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the venous return.”

20. Venous Legs swell Neck veins distend Liver congestion Lung congestion Arterial Decreased perfusion…. Brain Kidneys Everything...

21. CHF: Diagnosis CHF is a CLINICAL diagnosis n History n Physical Exam n Chest X Ray n EKG n Echocardiogram n Laboratory testing

22. How do you know an ED pt has Heart Failure? CHF: a CLINICAL diagnosis n History n Physical Exam n Chest X Ray n Echocardiogram n Laboratory testing …. Shortness of Breath!!! ; Leg edema; weakness …. Legs: Edema; Lungs: Rales

23. Accuracy of Diagnosis: CHF EMS : 50-65% Emergency Doc: 65-80% Cardiologist: 80-85% How do you know an ED pt has Heart Failure?

24. NEJM 02;347:161-167 OR’s for differentiating between patients with and those without CHF

25. Ask 3 Questions: 1. History of Congestive Heart Failure? 2. RALES on Lung Examination? 3. EDEMA to Legs? IN The Emergency Department: Do a Chest XRay How do you know an ED pt has Heart Failure?

26. Emergency Department

27. Spectrum of Heart Failure AsymptomaticCHF Dyspnea on exertion Cardiogenic Shock Pulmonary Edema PND and orthopnea Dyspnea at rest Moderate

28. Natriuretic Peptides: Origin and Stimulus of Release PeptidePrimary OriginStimulus of Release ANPCardiac atriaAtrial distension BNPVentricular myocardiumVentricular overload CNPEndothelium Shear stress of endothelium Adapted from Burnett JC, J Hypertens 2000;17(Suppl 1):S37-S43 ANP = Atrial Natriuretic Peptide BNP = B-type Natriuretic Peptide CNP = C-type Natriuretic Peptide

29. Adapted from Burnett JC, J Hypertens 1999;17(Suppl 1):S37-S43 RAAS (Renin-Angiotensin Aldosterone System) Activation of AT 1 receptors by angiotensin II Vasoconstriction Sodium retention Increased aldosterone release Increased cellular growth Increased sympathetic nervous activity NPS (Natriuretic Peptide System) ANP, BNP Vasodilation Sodium excretion Decreased aldosterone levels Inhibition of RAAS Inhibition of sympathetic nervous activity CNP Vasodilation Decreased vascular smooth muscle growth Decreased aldosterone levels

30. BNP Levels of 250 Patients Presenting with Dyspnea Mean BNP Concentration (pg/ml) Asymptomatic LV Dysfunction No CHF (n=14) 38 ± 4 141 ± 31 1076 ± 138 No CHF (n=139) CHF (n=97) 0 200 400 600 800 1000 1200 1400 Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85 P < 0.001

31. BNP Concentration for the Degree of CHF Severity BNP Concentration (pg/ml) 186 ± 22 791 ± 165 2013 ± 266 Mild (n=27) Moderate (n=34) Severe (n=36) 0 500 1000 1500 2000 2500 Maisel A. et al. J Am Coll Cardiol 2001;37(2):379-85

32. BNP Concentration for the Prediction of Clinical Events Harrison, Maisel Ann Emerg Med 2002;39:131-138 020406080100120140160180 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% BNP < 230 pg/ml BNP 230-480 pg/ml BNP > 480 pg/ml Death or Heart Failure Hospitalization Days

33. Rapid Measurement of BNP in Emergency Diagnosis of Heart Failure Multinational study at 7 centers: Baseline BNP-1586 ED dyspnea pts vs clinical judgment Mean BNP Concentration (pg/ml) Dyspnea due to noncardiac in pt with hx of LV dysfunction (n=72) No CHF (n=770) CHF (n=744) 0 200 400 600 800 1000 1200 1400 Maisel A. et al. NEJM 02;347:161-167

34. NEJM 02;347:161-167 OR’s for differentiating between patients with and those without CHF

35. BNP Integration -Diagnostic: CHF vs COPD -CHF Risk Stratification: mild, mod, severe disposition mortality -Therapeutic Decision-Making change therapy cease therapy BNP Integration -Diagnostic: CHF vs COPD -CHF Risk Stratification: mild, mod, severe disposition mortality -Therapeutic Decision-Making change therapy cease therapy

36. No Heart Failure, No Ventricle Stretch 400 100 Mild Ventricle Stretch: HF, PE, CM, ACS, Pulm HTN Significant Decompensated Heart Failure Mean BNP Concentration (pg/ml) Interpretation of the BNP Assay in the Dyspneic Patient

39. You’ll also hear about Pro-BNP Pro-BNP is the BNP precursor. It is degraded in the liver - bnp is a product and is ultimately cleaved by neutral peptidase: no renal or hepatic effects D R I M K R G S S S S G L G F C C S S G S GQ V M K V L R R H K P S

40. Ask 3 Questions: 1. History of Congestive Heart Failure? 2. RALES on Lung Examination? 3. EDEMA to Legs? How do you know an ED pt has Heart Failure? Shoot a Chest Xray Run a BNP level

41. Current Treatment of Acute Heart Failure

42. Diuretics Reduce fluid volume Vasodilators Decrease Preload And Afterload Inotropes Augment Contract- ility

43. Heart Failure Guidelines 1.ACC/AHA Task Force on Practice Guidelines. 2001 1.ACC/AHA Task Force on Practice Guidelines. 1995 2.Working Group for Heart Failure of the European Society of Cardiology. 1997 3.Advisory Council To Improve Outcomes Nationwide in Heart Failure. (ACTION – HF) 1999 4.HFSA Guidelines for Management of Patients With Heart Failure Caused by Left Ventricular Systolic Dysfunction - Pharmacological Approaches. 1999 Focus on…Omit… Stable outpatients Criteria for admission to hospital Systolic dysfunctionTailored hemodynamic treatments Decompensated patients 1. Circulation 1995;92:2764-2784, 2. Eur Heart J 1997;18:736-753, 3. Am J Cardiol 1999;83(2A):1A-38A, 4. Journal of Cardiac Failure 1999;5:357-382

44. Current Treatment of Acute Heart Failure Diuretics Reduce fluid volume Vasodilators Decrease Preload And Afterload Inotropes Augment Contract- ility LasixDopamine Lasix Ntg: sl, top, iv MSO4 ACEi BiPAP

45. Expose the Literature...

46. 06121824 Months 0 10 20 30 40 50 60 Total Mortality Risk% 199 257 PCW > 16 mmHg PCW < 16 mmHg P=0.001 06121824 Months 0 10 20 30 40 50 60 Total Mortality Risk% 236 220 Cardiac Index > 2.6 L/min-M 2 Cardiac Index < 2.6 L/min/M 2 Early Response of PCW but not CI Predicts Subsequent Mortality in Advanced Heart Failure Fonarow Circulation 1994;90:I-488 P=NS

47. You’ve also got to look at symptom improvement...

48. Let’s Start with the Ntg vs. Lasix Debate

49. Increasing dose of nitroglycerin VEINS Arteries

51. Historical Comparison for PCWP J Cardiovasc Pharmcol 1987. 10(1):38-46 n = 48 “acute severe ht. failure” pts

52. Historical Comparison for PCWP J Cardiovasc Pharmcol 1987. 10(1):38-46

53. Conclusion 1: Ntg better than Lasix Hi dose Ntg better than lo dose

54. Morphine?? n Hoffman. Chest 1987;92:586-593. “Adverse effects were found only in patients who received morphine.” (4 tx groups, 57 patients) n Cohen. Am J Emerg Med 2000;18:342-3.“Assertions that the use of MS in the tx of ACPE is appropriate or inappropriate are opinion only and not scientifically established.” n Sacchetti. Am J Emerg Med 1999;17:571-574. “Morphine sulfate’s use in acute pulmonary edema is difficult to justify based on the data in this and other studies. Its use resulted in higher intubation rates, ….and consequently higher ICU admission rates.”

55. 95% Conf I Am J Emerg Med 99;17:571-574: 181 pts

56. 95% Conf I Am J Emerg Med 99;17:571-574: 181 pts

58. Conclusion 2: Very little data on MSO4 MSO4 likely bad or at least, redundant to preload Sedation and Resp Failure?

59. Acute ACE therapy n Routes and selected agents are diverse: PO/SL/IV; Captopril, Lisinopril, Enalapril….etc….. n Barnett: Current Ther Research 1991. 49:274-281. o Report of 7 patients with Acute L heart failure given 12.5 or 25 mg SL Captopril q 30 minutes x 3: Significant PCWP reductions (25 -> 19 in 60 minutes) without large drops in BP, also documented substantial reductions in subjective orthopnea scores: “SL administered captopril provides..rapid serum conc, balanced vasodilation, and inhibition of Angiotensin II…and does not affect systemic BP in a deleterious manner.”

60. Acute ACE therapy n Haude: Intern Jour Cardiol 1990. 27:351-359. o Randomized cross-over design of 25 patients with Acute L heart failure given 25 mg SL Captopril or 0.8 mg SL Ntg: Significant PCWP reductions without large drops in BP: “SL administration of captopril was superior to nitroglycerin for some parameters. The temporal hemodynamic changes revealed an earlier start of action after nitroglycerin, but a later maximum and a longer persistance after captopril.” n Langes: Current Ther Research 1993. 53:167-176. o Report of 13 patients with Acute L heart failure given IV continuous infusion of Captopril: Significant PCWP reductions (more rapid than SL reports) without large drops in BP, also documented substantial reductions in ACE and aldosterone, although plasma renin increased.

61. Acute ACE: A RCT in the ED!!! SL Captopril 12.5 mg vs Placebo Acad EM 1996. 3:205-212 pts with APE Placebo = 25 Captopril = 23 Baseline treatment = 2mg increments MSO4 + 40mg min. lasix + sl Ntg +/- IV Ntg

62. Primry Outcome: Placebo vs Captpl APEX Score Acad EM 1996. 3:205-212 * = Stat Sig Minutes after Treatment * * APEX Score (nonvalidated): 1. Deg of orthopnea tolerance 2. Pt.-reported dyspnea 3. Observer-reported dyspnea 4. Observer-reported diaphoresis (conv score as % of time zero)

63. Acute ACE: Other Outcomes: SL Captopril 12.5 mg vs Placebo Acad EM 1996. 3:205-212 % No Statistical Differences in Any Groups

64. Conclusion 3: ACE acute therapy may be good No reason to see it as harmful

65. One more to go: the NVS question

66. BiPAP or CPAP?? n Multiple small case reports of Noninvasive Ventilatory Support (NVS) in patients with varying diagnoses of respiratory failure. n No assessment of hemodynamic findings in a controlled fashion.

67. BiPAP vs CPAP?? n Mehta. Crit Care Med 1997;25:620-628. One small study raising concern for BiPAP-associated AMI in pulmonary edema patients, compared to CPAP. 27 pts randomized with more rapid improvements in dyspnea and oxygenation associated with BiPAP: BiPAP and CPAP good, BiPAP = MI n Kosowsky. Am J Emerg Med 2000;18:91-95. Good review of literature to date on Noninvasive Ventilatory Support (NVS).

68. Other Evidence for BiPAP-assoc Badness: Isosorb Dinitrate (4 mg IV q 4 min) vs Isosorb/BiPAP (10mcg/min titrating by 10mcg/min) JACC 2000. 36:832-837 n = pts <90% Hi Ntg = 20 BpP/Ntg = 20 % * * * Baseline treatment = 3mg MSO4 + 80mg Lasix Sacchetti Letter 2001: Bipap pressures too low, MS bad and CK is artifact of BiPAP

69. Conclusion 4: Bipap: we just don’t know… But – we believe!

70. Historical CHF Conclusions: n The data is weak for all historical therapies n MSO4 implicated as a problem in a number of investigations... n IV Ntg appears efficacious and likely important as initial therapy…hi dose probably best. n BiPAP may be injurious at higher pressures but ineffective at lower… decreased intubation rates, mortality and other outcomes remain unproven. n ACE evidence: some symptom improvement, no mortality/ETI/AMI benefit proven to date..

72. Acute Heart Failure: New Drugs and Approaches Mfg byFDA

73. Nesiritide (h-BNP) is Identical to the Endogenous Naturally Occurring Hormone Clemens LE, Protter AA, et al. J Pharmacol Exp Ther 1998;287:67-71 Precise amino acid sequence Identical pharmacological profile D R I M K R G S S S S G L G F C C S S G S GQ V M K V L R R H K P S

74. More than diuresis...

75. It’s a neurohumoral experience...

76. Current Treatment of Acute Heart Failure Diuretics Reducefluidvolume Natriuretic Peptides Decrease Decrease Preload Preload And And Afterload Afterload Inotropes Augment Augment Contrac- Contrac- tility tility DecreaseVolumePreloadAfterloadAndNeuro-hormones Vasodilators

77. Ntg vs Nesiritide Nesiritide

78. Hours 0 Months 6 Eligible Patients (n = 489) Catheterized (n = 246) Non-Catheterized (n = 243) StratifiedRandomized Nitroglycerin (n = 60) Placebo (n = 62) Nes fixed-dose (n=62) Nes adjustable dose (n = 62) Nitroglycerin (n = 92) Nesiritide fixed-dose (n = 92) Nesiritide adjustable dose (n = 62) 3-Hour Placebo- Control Period Active- Control Period 1 2 3 Nitroglycerin (n = 124) Placebo (n = 80) Nesiritide fixed-dose (n = 119) Nitroglycerin (n = 83) Nes fixed-dose (n = 80) End of Study Drug VMAC Study Design Added to background Rx VMAC investigators. JAMA 2002; 287:1531-40

79. # * # * # * ## # p < 0.05 versus placebo * p < 0.05 versus NTG 15 m 30 m 1 hr 2 hr 3 hr BL Mean observed value (mmHg) Placebo Nitroglycerin Nesiritide 18 20 22 24 26 28 30 VMAC Primary Endpoint: PCWP through 3 Hours VMAC investigators. JAMA 2002; 287:1531-40

80. VMAC: PCWP Effects to 48 Hours Change from Baseline in PCWP (mmHg) End of Placebo-Controlled Period Time on Study Drug (Hours) † p < 0.05 Vs. IV NTG * p < 0.05 Vs. Placebo * †*†* VMAC investigators. JAMA 2002; 287:1531-40 †*†* †*†* †*†* * †*†* † † † † *

81. -10 0 10 20 30 40 50 60 70 80 90 100 Dyspnea at 3 hours Nesiritide Placebo NTG Improved (%) Worsened (%) P=0.034 P=0.191 No change VMAC Primary Endpoint VMAC investigators. JAMA 2002; 287:1531-40

82. VMAC: Dyspnea at 24 Hours Nitroglycerin (n=123/124) Nesiritide Fixed (n=118/119) -30 -20 -10 0 10 20 30 40 50 60 70 80 90 100 p=0.027 NitroglycerinNesiritide Dyspnea Non-Catheterized Subjects as Randomized VMAC investigators. JAMA 2002; 287:1531-40

83. Nesiritide and Six Month Mortality: Pooled Analysis of 4 Studies 0306090120150180 10 20 30 40 50 60 70 80 90 100 All Control (n = 443) All Nesiritide (n = 724) 6 Month Mortality Rate Nesiritide 21.5% vs. Control 21.7% RR 1.0 (95% CI 0.70 to 1.3) p=0.830 (All Treated Subjects, As Treated) Time from the Start of Treatment (days) Cumulative Mortality Rate (%) FDA Cardio-Renal Advisory Panel

84. CHF:The Evolving Therapeutic Approach Traditional EM Approach Lasix: Hi Dose Top/SL Ntg: Lo Dose IV MSO4 EMS: Ntg + Lasix Lasix: Lo Dose Top/SL/IV Ntg: Hi Dose Recent EM Approach Intubation Once the patient is free of congestion, discontinue therapy. ACEi - BiPAP Intubation

85. Emergency Department Patients with Acutely Decompensated Congestive Heart Failure: Is Discharge a Safe Disposition? Brewer AV, Burton JH, Strout TD Department of Emergency Medicine Maine Medical Center Portland, Maine

86. * 9% admitted to ICU * 52% admitted to telemetry * Mean Hospital LOS = 6.1 days 552 HF patients: 2000 Disposition in Acute CHF

87. 552 CHF Patients CY 2000

88. 90 CHF Patients Went Home... 2 deaths

89. n No rule performed well. n Incidence of death or complication ranged from 7% to 9% in the lowest risk groups. Comparison of 4 Clinical Prediction Rules for Estimating Risk in Heart Failure Disposition in Acute CHF Auble, Yealy: Ann EM: 2007

90. Ask 3 Questions: 1. History of Congestive Heart Failure? 2. RALES on Lung Examination? 3. EDEMA to Legs? How do you know an ED pt has Heart Failure? Shoot a Chest Xray Run a BNP level

91. CHF: Therapeutic Approach Lasix: Lo Dose Top/SL/IV Ntg: Hi Dose Once the patient is free of congestion, discontinue therapy. ACEi - BiPAP Intubation