1. Current treatment of acute heart failure Department of Cardiology of the University Medical Center Belgrade, Serbia Prof. Petar M. Seferović, MD, PhD, FESC, FESC Member of the Board, Heart Failure Association of the ESC

2. Natural history of congestive heart failure Initial phase Last year Normal heart Chronic heart failure 5 million in the US 10 million in Europe Death Initial myocardial injury First ADHF episode: Pulmonary edema ER admission Later ADHF episodes: Rescue therapy ICU admission Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G. Heart Viability

3. Acute heart failure is heterogeneous syndrome Cardiogenicshock PULMONARYEDEMA Right Heart Failure High Output Failure Hypertensive HF Acute Decompensated CHF Filippatos 2005

5. Diagnostic approach to acute heart failure

6. EVIDENCE Applying guidelines in acute heart failure: Facts or fancy?

7. ACCF/AHA Practice Guideline 40 pages

8. Canadian Cardiovascular Society Consensus Recomendations

9. Australia/New Zealand Heart Failure Guidelines

10. The etiology of acute heart failure can vary significantlly Primary dilated cardiomyopathy Acute coronary syndrom Arterial hypertension, diabetes mellitus Toxic cardiomyopathy (cocaine, alchohol)

11. Clinical and pathophysiological classification of acute heart failure More than 90% of patients hospitalized with heart failure have congestion (wet) and show elevated PCWP 1,2 References: 1. Stevenson LW. Tailored therapy to hemodynamic goals for advanced heart failure. Eur J Heart Fail. 1999;1:251-257. Available at: http://www.sciencedirect.com/science/journal/13889842. 2. Fonarow GC. The treatment targets in acute decompensated heart failure. Rev Cardiovasc Med. 2001;2(suppl 2):S7-S12. Warm & Dry PCWP* normal CI † normal (compensated) Warm & Wet PCWP elevated CI normal Cold & Dry PCWP low/normal CI decreased Cold & Wet PCWP elevated CI decreased Congestion at rest Low perfusion at rest Vasodilators, diuretics No Yes Normal SVRHigh SVR

12. Clinical presentations of acute heart failure in EHFS II and ALARM-HF studies ALARM-HF EHFS II Pulmonary oedema (16% vs 37%) and cardiogenic shock (4% vs 12%) are significantly different between the two studies.

13. ESC treatment algorithm for acute heart failure

14. ADHERE registry: Treatment of acute heart failure ADHERE (Acute Decompensated HEart Failure National REgistry) Data from >100.000 patients Database of demographic and clinical parameters of hospitalized patients with decompensated heart failure

15. Clinical presentation of acute heart failure in major clinical studies

17. Diuretics in acute heart failure: Proven and effective  CLINICALLY proven, pathophysiologically UNCLEAR  SYMPTOMATIC improvement  HEMODYNAMIC improvement  To increase DIURESIS  To improve OXYGEN SATURATION  CLINICALLY proven, pathophysiologically UNCLEAR  SYMPTOMATIC improvement  HEMODYNAMIC improvement  To increase DIURESIS  To improve OXYGEN SATURATION

18. Increasing mortality with intravenous furosemide in acute heart failure? Ahmed et al. European Heart Journal 2006 27, 1431–1439Hasselblad V, et al. HFSA, 2005. ESCAPE Trial

19. Vasodilatators in acute heart failure ä Intravenous nitrate/SNP (caution if SBP <110mmHg) ä Class I/level B

20. The VMAC Investigators. JAMA. 2002; 287: 1531 Subjects Improved (%) Subjects Worse (%) p values are based on Van Elteren test with 7 - point ordinal scale 0 10 20 30 40 50 60 70 80 10 90 100 NTG Nesiritide Placebo No Change p = 0.034 p = 0.191 30 days Readmissions20% 23% Acute heart failure: VMAC primary endpoint: Dyspnea at 3 hours.

21. Sackner-Bernstein JD, et al. JAMA. 2005;293:1900-1905. Mortality, % Days Nesiritide (n = 485) Control (n = 377) Unadjusted: hazard ratio 1.86 (95% CI, 1.02-3.41), P=0.04 Adjusted for study: hazard ratio 1.80 (95% CI 0.98-3.31), P=0.057 Meta-Analysis of 3 Nesiritide Trials* *NSGET, VMAC, and PROACTION trials Neseritide is associated with increasing mortality in acute heart failure

22. Treatment of acute heart failure according to blood pressure at presentation

23. Left ventricular filling pressures as the guide for the treatment of acute heart failure

24. Inotropes in the treatment of acute heart failure  Inotropes should be considered in patients with low output states  Most class IIa or IIb and level B!

25. ADHERE registry: Inotropic agents and mortality in acute heart failure Abraham WT, et al. JACC 2005;46(1):57–64. NTGNesiritide Milrinone Dobutamine

26. 0 0.25 0.50 0.75 1.00 0 0.25 0.75 1.25 1.50 Fraction Survived Follow-Up, year No Dobutamine (n = 391) Dobutamine (n = 80) P=0.0001* *For NYHA III-IV patients. O’Connor CM, et al. Am Heart J. 1999;138:78-86. FIRST Trial: Adjusted Survival EFFECT OF DOBUTAMINE ON SURVIVAL

27. OPTIME-CHF Trial: Sub-Group Survival Milrinone Non-ischemic Milrinone Ischemic Placebo Ischemic Placebo Non-ischemic 100 98 96 94 92 90 88 86 0 10 20 30 40 50 60 Days Survival, % Felker GM, et al. J Am Coll Cardiol. 2003;41:997-1003. Cuffe MS, et al. JAMA. 2002;287:1541-1547. EFFECT OF MILRINONE ON SURVIVAL Kaplan-Meier survival curves (at 60 days, by heart failure etiology and treatment)

28. Ca 2+ Levosimendan DiastoleSystole Pollesello P, et al. J Biol Chem. 1994;269:28584-28590. Sorsa T, et al. Mol Cell Biochem. 2004;266:87-107. Levosimendan Binding to Troponin C

29. 180 day all-cause mortality SURVIVE Levosimendan (n = 664) 173 (26%) Dobutamine (n = 663) 185 (28%) Hazard Ratio (CI) 0.91 (0.74-1.13) P-Value 0.401 ∆ Deaths - 12 5d 31d 180d

30. Treatment of acute heart failure Balancing RISKS AND BENEFITS for individual patients! CHF

31. ESCACC/AHACanadian OxygenI C - Loop diureticI B VasodilatorsI BIIa CI B Non-invasive ventilationIIa B- InotropesIIa BI C/IIb CI B Invasive monitoringIIa B/IIa CI C/IIa CI B UltrafiltrationIIa B None Coronary reperfusionI CIIa CNone No class of drugs has reccomendation level of evidence A ! Treatment of acute heart failure Comparison of various treatment modalities in different guidelines

32. FAST FACTS  Experts from five leading European associations  Agreed on cosensus document on the treatment of acute heart failure in Europe

33. Medical decisions were always tough to make