Current treatment of acute heart failure

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

2. Natural history of congestive heart failure Normal heart Chronic heart failure5 million in the US10 million in Europe Death Initial myocardial injury Heart Viability First ADHF episode:Pulmonary edemaER admission Later ADHF episodes:Rescue therapyICU admission Last year Initial phase Gheorghiade M. Am J Cardiol. 2005;96(suppl 6A):1-4G.

3. Acute heart failure is heterogeneous syndrome Right Heart Failure PULMONARY EDEMA Cardiogenic shock High Output Failure Acute Decompensated CHF Hypertensive HF Filippatos 2005

5. Diagnostic approach to acute heart failure

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

7. ACCF/AHA Practice Guideline 40 pages

8. Canadian Cardiovascular Society Consensus Recomendations

9. Australia/New Zealand Heart Failure Guidelines

10. The etiology of acuteheart failurecan vary significantlly • Acute coronary syndrom • Arterial hypertension, diabetes mellitus • Primary dilated cardiomyopathy • Toxic cardiomyopathy (cocaine, alchohol)

11. Clinical and pathophysiological classification of acute heart failure Congestion at rest No Yes No Vasodilators,diuretics Low perfusionat rest Yes Normal SVR High SVR More than 90% of patients hospitalized with heart failure have congestion (wet) and show elevated PCWP1,2 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.

12. Clinical presentations of acute heart failurein EHFS II and ALARM-HF studies EHFS II ALARM-HF 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

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

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

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

21. Nesiritide (n = 485) Mortality, % Control (n = 377) Days Neseritideis associated with increasing mortality in acute heart failure Meta-Analysis of 3 Nesiritide Trials* 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 *NSGET, VMAC, and PROACTION trials Sackner-Bernstein JD, et al. JAMA. 2005;293:1900-1905.

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 NTG Nesiritide Dobutamine Milrinone Abraham WT, et al. JACC 2005;46(1):57–64.

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

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

28. Levosimendan Binding to Troponin C Ca2+ Levosimendan Diastole Systole Pollesello P, et al. J Biol Chem. 1994;269:28584-28590. Sorsa T, et al. Mol Cell Biochem. 2004;266:87-107.

29. 5d 31d SURVIVE 180 day all-cause mortality 180d ∆ Deaths - 12

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

31. Treatment of acute heart failure Comparison of various treatment modalities in different guidelines No class of drugs hasreccomendation level of evidenceA !

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