acute heart failure:therapeutic update


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acute heart failure:therapeutic update

  1. 1. Algorithm for management of acute heart failure Current therapeutic strategies Novel therapeutic strategies Newer inotropic drugs New Recommendations for the Hospitalized Patient
  2. 2. Acute heart failure is a heterogeneous syndrome with multiple presentations
  3. 3. 3% 50% 47% Suggested initial triage in patients with suspected AHF syndromes
  4. 4. Suggested treatment algorithm for patients with hypertensive AHF syndromes.
  5. 5. Suggested treatment algorithm for patients with normotensive AHF syndromes.
  6. 6. Suggested treatment algorithm for patients with hypotensive AHF syndromes.
  7. 7. What Should be the Goals of Therapy of AHF? • Make the patient feel better: reduce dyspnea and improve QOL • Reduce Mortality • Reduce Rehospitalization • Do it safely
  8. 8. Various targets for therapies used in the management of acute heart failure.
  9. 9. Current Treatment of Acute Heart Failure Use in ADHERE Registry 88% 21 Diuretics Vasodilators Reduce Fluid Volume Decrease Preload and/or Afterload (Na+&H20) 15% Inotropes Augment Contractility
  10. 10. Vasodilators Loop diuretics Used in 88% of cases 10% 1% 10% Inotropics 6% 6% 3% ?
  11. 11. Novel therapeutic targets for the treatment of acute heart failure
  12. 12. Sites of action of drugs producing diuresis and natriuresis. Rolofylline Tolvaptan
  13. 13. Sites of action of vasodilators. Ularitide Relaxin Nesiritide
  14. 14. Sites of action of inotropic agents. Istaroxime Levosimendan Omecamtiv mecarbil
  15. 15. Why do new agents fail in Phase III trials? In recent years a repeated finding, particularly in clinical trials of patients with AHF, is that the positive results that are observed in preclinical and Phase II studies are not confirmed in large Phase III RCTs.
  16. 16. A Word About Inotropes. In the setting of AHF, inotropic agents are only recommended in patients with SBP 90 mmHg and evidence of inadequate organ perfusion despite other therapeutic interventions.
  17. 17. Issues with Current Inotropes Initial choice of therapy Weaning Patient related variables Differences in efficacy Adverse effect profile Survival data “Long-term” infusions There is an urgent clinical need for agents that improve cardiac performance with a favourable safety profile.
  18. 18. Inotropic mechanisms and drugs Inotropic mechanism Drugs Sodium-potassium-ATPase inhibition Digoxin b-Adrenoceptor stimulation Dobutamine, dopamine Phosphodiesterase inhibition Enoximone, milrinone Calcium sensitization Levosimendan Sodium-potassium-ATPase inhibition plus SERCA activation Istaroxime Acto-myosin cross-bridge activation Omecamtiv mecarbil SERCA activation Gene transfer SERCA activation plus vasodilation Nitroxyl donor; CXL-1020 Ryanodine receptor stabilization Ryanodine receptor stabilizer; S44121 Energetic modulation Etomoxir, pyruvate
  19. 19. Results of the recent AHF trials (disappointing) Study Patients Primary End Point Calcium Sensitizer (Levosimendan) LIDO CASINO 203 299 REVIVE II 600 SURVIVE 800 Change CI 24 h and PCWP 24 h Mortality 30 d and Mortality 180 d Composite global assess. at 6 h, 24 h 5 d Mortality 180 d SERCA agonist & Na/K ATPase inhibitor (Istaroxime) HORIZON-HF 120 PCWP Changes from baseline
  20. 20. ATOMIC-AHF (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure) ESC Congress 2013 in Amsterdam
  21. 21. Calcium sensitizers Levosimendan (Simdax®) increases sensitivity of troponin in the heart to calcium. This results in increased myocardial contractility. It is infused i.v. for short treatment of AHF.
  22. 22. Levosimendan : ESC Guidelines 2012 Patients with hypotension, hypoperfusion or shock An i.v. infusion of levosimendan (or a phosphodiesterase inhibitor) may be considered to reverse the effect of ẞ -blockade if ẞ -blockade is thought to be contributing to hypoperfusion. • The ECG should be monitored continuously because inotropic agents can cause arrhythmias and myocardial ischaemia, • and, as these agents are also vasodilators, blood pressure should be monitored carefully. Class of recommendation IIb . Level of evidence C
  23. 23. New Recommendations for the Hospitalized Patient 2013 ACCF/AHA Guideline for the Management of Heart Failure A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
  24. 24. The Major Reason for Heart Failure Hospitalizations Worsening chronic heart failure (75%) De novo heart failure (23%) Advanced/ end-stage heart failure (2%) Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21 Cleland JG et al. Eur Heart J. 2003; 24: 442
  25. 25. Therapies in the Hospitalized HF Patient Recommendation HF patients hospitalized with fluid overload should be treated with intravenous diuretics HF patients receiving loop diuretic therapy, should receive an initial New parenteral dose greater than or equal to their chronic oral daily dose, then should be serially adjusted COR LOE I B I B
  26. 26. Therapies in the Hospitalized HF Patient Recommendation When diuresis is inadequate, it is New reasonable to a) Give higher doses of intravenous loop diuretics; or b) add a second diuretic (e.g., thiazide) COR LOE IIa B
  27. 27. Therapies in the Hospitalized HF Patient Recommendation COR LOE Low-dose dopamine infusion may be considered with loop diuretics to improve diuresis New IIb B Ultrafiltration may be considered for patients with refractory congestion New IIb C Intravenous nitroglycerin, nitroprusside or nesiritide may be considered an adjuvant to diuretic therapy for stable patients with HF IIb A New
  28. 28. Therapies in the Hospitalized HF Patient Recommendation COR LOE HFrEF patients requiring HF hospitalization on GDMT should continue GDMT unless hemodynamic instability or contraindications New I B Initiation of beta-blocker therapy at a low dose is recommended after optimization of volume status and discontinuation of intravenous agents I B New
  29. 29. Recommendations for Inotropic Support Recommendations Cardiogenic shock pending New definitive therapy or resolution Short-term support for threatened end-organ dysfunction in hospitalized patients with stage D and severe HFrEF New Short-term intravenous use in hospitalized patients without evidence of shock or threatened end-organ performance is potentially harmful New COR LOE I C IIb B III: Harm B