1 / 51

Therapeutic Algorithm in Heart Failure

Therapeutic Algorithm in Heart Failure. Joseph Elias, MD May 22, 2004 Beirut - LEBANON. Prevalence and Prognosis of HF in USA. 2 million Heart Failure patients in the US in 1997 28 billions US$ in 1996 for congestive HF 400,000 new cases per year

vincent
Télécharger la présentation

Therapeutic Algorithm in Heart Failure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Therapeutic Algorithm in Heart Failure Joseph Elias, MD May 22, 2004 Beirut - LEBANON

  2. Prevalence and Prognosis of HF in USA • 2 million Heart Failure patients in the US in 1997 • 28 billions US$ in 1996 for congestive HF • 400,000 new cases per year • Sudden cardiac death (SCD) may occur in as many as 40% of all Heart Failure patients

  3. Prevalence and Prognosis of HF in Europe • Estimates range from 0.4% to 2% • Increase rapidly with age • High prevalence • 10 million patients with HF • 10 million patients with myocardial dysfunction • 50% of patients with HF will die within 4 years • > 50% of patients with severe HF will die within 1 year Task force for the Diagnostic and Treatment of Chronic Heart Failure ESC. European Heart Journal 2001;22:1527-1560

  4. Prevalence and Prognosis of HF in France • 500,000 Heart Failure patients in France in 2001 • Increase by 120,000 per year • The incidence rises from: • 0.4% of male and 0.3% of females aged between 55 and 64 years to • 5% of males and 8.5% of females aged between 85 to 94 years • 3.5 million consultations and 150,000 hospitalizations for HF per year • The cost linked to HF represents more than 1% of total medical cost

  5. Prevalence and Prognosis of HF in Lebanon

  6. The Epidemiological Aspects and Etiological Basis of Heart Failure Alan J. Cowley in: International Handbook of Heart Failure, 1994, pp 13-17 percent 70 Ischemic Heart Disease (IHD) 60 Dilated cardiomyopathy (CMO) 50 Primary valvular disease 40 30 n = 552 20 10 0 IHD CMO Valvular Hypertension Other R.W. Timmers, M.D.

  7. The two main endpoints in progressive Heart Failure are: Sudden Cardiac Death (SDC)is the leading cause of death in NYHA class I and II Progressive left ventricular dysfunction leading to death by pump failure, occurring mainly in NYHA class III and IV R.W. Timmers, M.D.

  8. Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97 Sudden Death by severity of Heart Failure symptoms NYHA ClassAnnual Mortality(%) SCD(%) II 5-15 50-80 (Mainly arrythmias) III 20-50 30-50 IV 30-70 5-30 (Mainly pump failures) R.W. Timmers, M.D.

  9. Aim of the Treatment • Prevention of disease leading to heart failure. • Prevention of progression to heart failure. • Morbidity: maintenance or improvement in quality of life. • Mortality: increase duration of life.The aims of CHF therapy are to improve hemodynamics and tolerance of exercise.

  10. Non Pharmacological Therapy • General advise and measures. • Educate patients and family. • Weight Control. • Dietary Measures. • Smoking • Travelling • Sexual activity • Exercise and exercise training

  11. Pharmacological Therapy • Diuretics. • ACE inhibitors. • Cardiac Glycosides. • β-Blockers. • ARBS • Aldosterone antagonists • Vasodialtor agents • Positive inotropic agents • Anticoagulation • Antiarrhythmic agents • Oxygen

  12. Device and surgery Therapy • Pace maker therapy • Biventricular stimulation • Heart Surgery • Circulation Support Systems • AICD

  13. Diuretics • LOOP DIURETICS, THIAZIDES AND METOLAZONE • Diuretics are essential for symptomatic treatment when fluid overload is present, although there are no controlled randomized trials that have assessed the effect on survival of these agents • They should always be administered in combination with ACE inhibitors • Aldosterone receptor Antagonists – Spironolactone • Aldosterone antagonist is recommended in advance HF in addition to ACE inhibitors and Diuretics to improve survival and morbidity • The RALES mortality trial showed that low dose Spironolactone (12.5 – 50 mg) on top of an ACE inhibitor and a loop diuretic markedly and progressively improved survival of patients in advanced NYHA III/IV HF, irrespective of aetiology

  14. β-BLOCKERS There are different types of β-Blockers: • Those that selectively inhibit Beta1 receptors. • Those that inhibit Beta1 and Beta2 receptors. • Those that inhibit Beta1, Beta2 and Alpha1 receptors.

  15. β-BLOCKERS • Interfere with the endogenous nervous system. • Inhibit the effects of the sympathetic nervous system (epinephrine and nor epinephrine). • Reduce sympathetic activity: - Prevention of catecholamine toxicity. - Reduction of myocardial ischemia. - Reduction of arrhythmias.

  16. β Blockade in Heart Failure • Consensus recommendations • all patients with class II-III heart failure due to left ventricular systolic dysfunction should receive a β blocker (in addition to an ACE inhibtor) unless they have contraindication to its use or cannot tolerate treatment with the drug • The results fo the CIBIS II study with Bisoprolol and the COPERNICUS study with Carvedilol have considerably contributed to increasing the evidence regarding the use of β-blockers in NYHA IV patients

  17. Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97 ACE inhibitors for the prevention of SDC inHeart Failure SUDDEN DEATH MORTALITY Study NYHA Follow-up MortalityACE no ACE p Class (mo) Decrease Consensus 1 IV 12 27% (p=0.003) 11.0 11.0 > 0.25 SOLVD RX II, III 41 16% (p=0.004) 8.2 8.8 > 0.25 SOLVD Prev. I, II 37 8% (p=0.30) 4.6 5.0 0.10 Overall6.2 6.6 0.09 R.W. Timmers, M.D.

  18. Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97 ACE inhibitors for the prevention of SDC inPost-MI w/o clinical signs of heart failure (early intervention) SUDDEN DEATH MORTALITY Study NYHA Follow-up MortalityACE no ACE p Class (mo) Decrease SAVE I 42 19% (p=0.019) 5.6 6.7 > 0.25 TRACE I, II 24-50 22% (p=0.001) 12.0 15.2 0.025 SMILE. I, II 1.5 22% (p=0.17) 0.5 1.4 0.17 Overall (Including AIRE Study)7.7 9.7 0.015 R.W. Timmers, M.D.

  19. ACE inhibition in Myocardial Infarction, LV Dysfunction and Heart Failure: Mortality Studies Trials Odds Ratio (& C. Limits) Risk Reduction % Myocardial infarction + 10 + 9 < 24 hrs Consensus-2 GISSI-3 - 11 + 5 ISIS-4 - 5 + 3 Chinese AMI - 3 + 6 Subtotal: - 6 + 2 MI with LV dysfunction - 19 + 9 Days SAVE - 22 + 7 TRACE - 8 + 8 Months SOLVD - 13 + 6 Subtotal: MI and Heart Failure - 27 + 9 Days AIRE - 8 %+ 2 Overall Treatment effect 2P = 0.003 0.5 0.75 1.0 1.25 R.W. Timmers, M.D.

  20. Angiotensin Receptor Blockers (ARBs) in Heart Failure Substitute or adjunctive therapy to ACE inhibitors ?

  21. ARBs in Heart Failure A meta-analysis of 17 studies in HF (n=12 469) • Patients with HF NYHA class II to IV • Studies comparing ARBs to placebo or ACE inhibitors • Randomized, blinded, parallel-group studies • Treatment duration of at least 4 weeks • Studies reporting death and hospitalization for HF Jong P et al. J Am Coll Cardiol 2002;39:463-70

  22. ARBs in Heart Failure Conclusions of the Meta-analysis • ARBs were not superior to controls in the pooled rates of death or hospitalization • There was a NS trend in favor of ARBs over placebo in reducing mortality and hospitalization when given without background ACEIs • When compared directly with ACEIs, ARBS were not superior in reducing either mortality or hospitalization • ARB+ACEI combinations were superior to ACEIs alone in reducing hospitalization but not mortality Jong P et al. J Am Coll Cardiol 2002;39:463-70

  23. CHARM-Alternative: Primary outcome CV death or CHF hospitalisation % 50 406 (40.0%) Placebo 40 334 (33.0%) 30 Candesartan 20 10 HR 0.77 (95% CI 0.67-0.89), p=0.0004Adjusted HR 0.70, p<0.0001 0 0 1 2 3 3.5 years Number at risk Candesartan 1013 929 831 434 122 Placebo 1015 887 798 427 126

  24. CHARM-Alternative Secondary outcomes p-value Placebo Candesartan 0.85 CV death 219 252 CHF hosp. 207 286 CV death, CHF hosp, 353 420 MI CV death, CHF hosp, 369 432 MI, stroke CV death, CHF hosp, 396 456 MI, stroke, revasc 0.072 0.68 <0.0001 0.78 0.0007 0.80 0.001 0.81 0.002 0.6 0.8 1.0 1.2 1.4 candesartan better Hazard ratio placebo better

  25. CHARM-Added:Primary outcomeCV death or CHF hospitalisation % 50 538 (42.3%) Placebo 40 483 (37.9%) 30 Candesartan 20 10 HR 0.85 (95% CI 0.75-0.96), p=0.011Adjusted HR 0.85, p=0.010 0 0 1 2 3 3.5 years Number at risk Candesartan 1276 1176 1063 948 457 Placebo 1272 1136 1013 906 422

  26. CHARM-Added Secondary outcomes p-value Placebo Candesartan 0.84 CV death 302 347 CHF hosp. 309 356 CV death, CHF hosp, 495 550 MI CV death,CHF hosp, 512 559 MI, stroke CV death,CHF hosp, 548 596 MI, stroke, revasc 0.029 0.83 0.014 0.85 0.010 0.87 0.020 0.87 0.015 0.6 0.8 1.0 1.2 1.4 candesartan better Hazard ratio placebo better

  27. Valsartan Valsartan + Captopril Captopril VALLIANT studyCV Death, MI, or HF by Treatment 0.4 0.3 Probability of Event 0.2 0.1 Valsartan vs. Captopril: HR = 0.96; P = 0.198 Valsartan + Captopril vs. Captopril: HR = 0.97; P = 0.369 0 Months 0 6 12 18 24 30 36 Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349

  28. SAVE TRACE AIRE Combined VALIANT (imputed placebo) 0.5 1 2 Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349 Summing up ACEI & ARBs in post MIMortality in SAVE, TRACE, AIRE, and VALIANT Hazard Ratio for Mortality Valsartan preserves 99.6% of mortality benefit of captopril. FavorsActive Drug FavorsPlacebo

  29. Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97 Antiarrythmicsfor the prevention of SDC inHeart Failure Class I Antiarrythmics: CAST 1 & 2 showed no evidence of preventing SCD in Heart Failure (Encainide, Flecainide) BASIS study (moricizine) showed a non significant increase in mortality... Amiodarone showed mixed results in primary SCD prevention in Heart Failure: CHF-STAT (US) trial showed no difference, except for non-ischemic cardiomyopathy Heart Failure patients (trend-wise) GESICA (Argentina) showed a significant mortality reduction for both pump failure and SCD. (60% of patients had non-ischemic cardiomyopathy) CAMIAT(Canada), and EMIAT(UK) trials in post MI showed a significant 35% reduction in SCDbut no decrease in overall mortality... R.W. Timmers, M.D.

  30. Cardiac Glycosides • Cardiac glycosides are indicated in AF and at any degree of symptomatic HF • In sinus rhythm, cardiac glycosides are recommended to improve the clinical status of patients with persisting HF symptoms due to LV systolic dysfunction despite ACE inhibitors and diuretic treatments • In the DIG Trial in 6,800 patients wth an ischaemic and non-ischaemic cardiomyopathy and mild to moderate HF, with long term digoxin, reduced symptoms, improved clinical status without any impact on survival

  31. Surgery • Surgical treatment should be directed towards the underlying aetiology and mechanisms. In addition to revascularization, it is important to approach patients with significant valvular disease before they develop significant LV dysfunction • Cardiomyoplsty cannot be recommended for treatment of HF • Heart transplantation is an accepted mode of treatment for end stage HF. Although, controlled trials have never been conducted, it is considered to significantly increase survival and quality of life (5 years survival70-80%)

  32. Cardiac Resynchronization Therapy for Heart FailureMechanisms, Clinical Outcomesand Patient Selection

  33. Ventricular Dysynchrony and Cardiac Resynchronization • Ventricular Dysynchrony1 • Electrical: Inter- or Intraventricular conduction delays typically manifested as left bundle branch block • Structural: disruption of myocardial collagen matrix impairing electrical conduction and mechanical efficiency • Mechanical: Regional wall motion abnormalities with increased workload and stress—compromising ventricular mechanics • Cardiac Resynchronization • Therapeutic intent of atrial synchronized biventricular pacing • Modification of interventricular, intraventricular, and atrial-ventricular activation sequences in patients with ventricular dysynchrony • Complement to optimal medical therapy 1 Tavazzi L. Eur Heart J 2000;21:1211-1214

  34. Cardiac Resynchronization Improved Intraventricular Synchrony Improved Atrioventricular Synchrony Improved Interventricular Synchrony Proposed Mechanisms of Cardiac Resynchronization Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445

  35. Cardiac Resynchronization Intraventricular Synchrony Atrioventricular Synchrony Interventricular Synchrony  RV Stroke Volume  dP/dt,  EF,  CO ( Pulse Pressure)  LA Pressure  LV Diastolic Filling  MR  LVESV  LVEDV Reverse Remodeling Summary of Proposed Mechanisms Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445

  36. HF and CRT Clinical Studies – Observational and Randomized

  37. 1Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026- 2033 2 Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4:311-320 3 Kuhlkamp V. JACC 2002;39:790-797 4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118 5Abraham W, Fisher W, Smith A, et al.N Engl J Med. 2002;346:1845-1853 6 Leon A. NASPE Scientific Sessions – Late Breaking Clinical Trials. May 2002; Medtronic Inc. data on file CRT Improves Quality of Life Score and NYHA Functional Class QoL NYHA PATH-CHF1 (n=41) ++ InSync (Europe)2 (n=103) ++ InSync ICD (Europe)3 (n=84) ++ MUSTIC4 (n=67) + MIRACLE5 (n=453) ++ MIRACLE ICD6 (n=364) ++ +Statistically significant improvement with CRT (p  0.05)  Not statistically significant or No statistical analysis performed on dataBlank Indicates test neither performed nor reported

  38. 6 Min Walk Peak VO2 Exercise Time PATH-CHF1 (n=41) ++ InSync (Europe)2 (n=103) + InSync ICD (Europe)3 (n=84) + MUSTIC4 (n=67) + MIRACLE5 (n=453) +++ MIRACLE ICD6 (n=364) ++ 1Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026- 2033 2 Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4:311-320 3 Kuhlkamp V. JACC 2002;39:790-797 4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118 5Abraham W, Fisher W, Smith A, et al.N Engl J Med. 2002;346:1845-1853 6 Leon A. NASPE Scientific Sessions – Late Breaking Clinical Trials. May 2002; Medtronic Inc., data on file CRT Improves Exercise Capacity +Statistically significant improvement with CRT (p  0.05)  Not statistically significant or No statistical analysis performed on dataBlank Indicates test neither performed nor reported

  39. 1Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026- 2033 2 Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4:311-320 3 Kuhlkamp V. JACC 2002;39:790-797 4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118 5Abraham W, Fisher W, Smith A, et al.N Engl J Med. 2002;346:1845-1853 6 Young J. ACC Scientific Sessions – Late Breaking Clinical Trials III. March 2002; Medtronic Inc., data on file CRT Improves Cardiac Function/Structure +Statistically significant improvement with CRT (p  0.05)  Not statistically significant or No statistical analysis performed on dataBlank Indicates test neither performed nor reported

  40. Cardiac Resynchronization OutcomesSustained for at least 12 months +Statistically significant improvement with CRT (p  0.05) No statistically significant improvement with CRTBlank Indicates test neither performed nor reported 1 Gras D, Leclercq C, Tang A, et al. Eur J Heart Fail 2002;4:311-320 2Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026-2033 3 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118

  41. PATH-CHF1 MUSTIC2 MIRACLE3 MIRACLE ICD4 1 year prior to implant, 22 patients hospitalized for HF with average stay of 18.5 days One year following implant, 9 patients hospitalized for HF with average stay of 4.5 days Sinus Rhythm Group: 7 times fewer hospitalizations for HF (12 month F/U) AF Group: 4 times fewer hospitalizations for HF (12 m/fu) Number of HF-hospitalizations significantly reduced (p = 0.02) Length of stay for HF-hospitalizations significantly reduced (p = 0.05) Cardiac Resynchronization BenefitsRelative to Hospitalization 1Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026-2033 2 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118 3Abraham W, Fisher W, Smith A, et al. N Engl J Med. 2002;346:1845-1853 4 Leon A. DeLurgioD, Smith A, et al. PACE 2002;25(4), Part II:647

  42. In Summary Cardiac Resynchronization therapy offers an adjunctive approach for treating selected patients with ventricular dysynchrony and moderate to severe heart failure who remain symptomatic despite optimal, stable medical therapy.

  43. CHF- Choice of Pharmacological therapy

  44. CHF- Choice of Pharmacological therapy

More Related