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MANAGING CONGESTIVE HEART FAILURE

MANAGING CONGESTIVE HEART FAILURE. Annual Conference of the Lebanese Society of Family Medicine Antoine Sarkis, MD Associate Professor of Cardiology Hotel Dieu de France Hospital. Guidelines. ESC HFSA CCS ACC/AHA. 2005. NYHA Classification. 2006. 2006. Four stage classification.

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MANAGING CONGESTIVE HEART FAILURE

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  1. MANAGING CONGESTIVE HEART FAILURE Annual Conference of the Lebanese Society of Family Medicine Antoine Sarkis, MD Associate Professor of Cardiology Hotel Dieu de France Hospital

  2. Guidelines • ESC • HFSA • CCS • ACC/AHA 2005 NYHA Classification 2006 2006 Four stage classification 2005

  3. Stages in the Evolution of Heart Failure. Clinical Characteristics Hypertension Diabetes, Hyperchol. Family Hx Cardiotoxins A B Heart disease (any) Asymptomatic LV dysfunction Systolic / Diastolic C Dyspnea, Fatigue Reduced exercise Tolerance (current or past) D Marked symptoms at rest despite max. therapy AHA / ACC HF guidelines 2001

  4. Classification of Recommendation • Class I: General agreement or evidence that a therapy is beneficial ►(therapy is recommended) • Class II: Conflicting evidence • IIa: evidence in favor of efficacy ►( therapy should be considered) • IIb: evidence less well established ►( therapy may be considered) • Class III: Not recommended, may be harmful

  5. Level of evidence • Level A: multiple randomized clinical trials or meta-analysis • Level B: single randomized trial, or non randomized studies • Level C: Consensus opinion of experts

  6. Treatment Objectives • Mainly decrease symptoms and prolong life • But also: • Decrease morbidity (hospital admissions, embolism…) • Increase exercise capacity and improve quality of life • Control neurohormonal changes • Retard progression of CHF

  7. Treatment of CHF • Control of risk factors • Life style • Treat etiologic cause / aggravating factors • Drug therapy • Revascularization • ICD (Implantable Cardiac Defibrillator) • Ventricular resynchronization (CRT) • Ventricular assist devices • Heart transplant • Artificial heart • Neoangiogenesis, Gene therapy All Selected patients

  8. Correction of reversible causes • Ischaemia • Valvular heart disease • Thyrotoxicosis and other high output status • Shunts • Arrhythmia • Atrial fibrillation, flutter, • Medications • Ca channel blockers, some antiarrhythmics

  9. Pharmacologic Therapy • Diuretics • ACE inhibitors • Beta Blockers • ARBs • Digitalis • Spironolactone • Other

  10. Diuretics. Indications • Symptomatic HF, with fluid retention • Peripheral edema • Dyspnea/ Pulmonary edema (Xray) • Jugular distension • Hepatomegaly AHA / ACC HF guidelines 2005 ESC HF guidelines 2005

  11. K+, Mg+ (15 - 60%) (sudden death ???) • Na+ • Hyperuricemia (15 - 40%) • Stimulation of neurohormonal activity • Hypotension. Pre-renal azotemia, Ototoxicity, Gastrointestinal, Metabolic Alkalosis. • Skin rashes, Neutropenia, Thrombocytopenia Adverse Effects of Diuretics.

  12. Inhibitors of renin-angiotensin- aldosterone system • Renin-angiotensin-aldosterone system is activated early in the course of heart failure and plays an important rolein the progression of the syndrome

  13. RAAS Blockade Angiotensin Converting Enzyme Inhibitors (ACE-I) Angiotensin Receptor Blockers (ARB)

  14. ACE-I. Clinical Effects in CHF • Improve symptoms • Reduce remodeling / progression • Reduce hospitalization • Improve survival

  15. CONSENSUS N Engl J Med 1987;316:1429 ACE-I 0.8 0.7 Placebo 0.6 Probability of Death p< 0.001 0.5 0.4 p< 0.002 0.3 Enalapril 253 patients NYHA IV 0.2 31 % 0.1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months

  16. 50 40 30 20 10 0 SOLVD (Treatment)N Engl J M 1991;325:293 ACE-I p = 0.0036 Placebo n=1284 % Mortality Enalapril n=1285 N = 2589 CHF - NYHA II-III - EF < 35 % 48 0 6 12 18 24 30 36 42 Months

  17. SAVE N Engl J Med 1992;327:669 ACE-I 30 Asymptomatic ventricular dysfunction post MI Placebo n=1116 20 Mortality % Captopril n=1115 10 N = 2231 3 - 16 days post AMI EF < 40 % 12.5 --- 150 mg / day ² -19% p=0.019 0 0 3 4 1 2 Years

  18. AIRE Lancet 1993;342:821 ACE-I Placebo 30 Mortality % 20 Ramipril 10 p = 0.002 N = 2006 HF after AMI 0 0 6 12 18 24 30 Months

  19. ACE-I Indications • Symptomatic heart failure (stage C) • Asymptomatic ventricular dysfunction • LVEF <35-40 % (stage B) • Patients with recent or remote history of MI regardless of EF or presence of HF (stage B) Class I recommendation Level of evidence A AHA / ACC HF guidelines ESC HF guidelines

  20. ACE-I. Practical Use • Start with very low dose • Renal function & serum K+ after 1-2 w • In the absence of fluid retention, ACE-I should be given first / In the presence of fluid retention together with diuretics • Dose NOT determined by symptoms. ACE-I should be up-titrated to dosages shown to be effective in clinical trials

  21. ACE-I. Adverse Effects • Hypotension (1st dose effect) • Worsening renal function, Hyperkalemia • Cough • Angioedema • Rash, ageusia, neutropenia, … • Pregnancy is a contra indication

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

  23. Potential advantages of ARBs • ARBs more effective than ACE-Idue to: • - Better RAAS Blockade • - Absence of angiotensin II escape • - Placebo like side effects

  24. ELITE II: Endpoint Results 1.0 0.8 All-cause mortality Probability of Survival 0.6 Losartan P = .16 0.4 Captopril 0.2 0.0 1.0 0.8 Sudden death or resuscitated arrest Event-free Probability 0.6 P = .08 0.4 0.2 0 1.0 0.8 Event-free Probability 0.6 P = .18 0.4 All-cause mortality or hospital admission 0.2 0 0 100 200 300 400 500 600 700 Follow-up (days) (Reprinted with permission from Pitt B, et al. Lancet. 2000)

  25. Val-HeFT: Study Design and Inclusion Criteria 5010 patients EF < 40%; NYHA II - IV Receiving background therapy ACEIs (93%), diuretics (86%),digoxin (67%), beta-blockers (35%) Randomized to Valsartan 40 mg bid titrated to 160 mg bid Placebo (Cohn JN, et al. N Engl J Med. 2001)

  26. 1.0 p = 0.80 0.9 Survival probability (%) Valsartan 0.8 0.7 0 3 6 9 12 15 18 21 24 27 Time since randomisation (months) Effect of Valsartan on Combined Mortality and Morbidity End Point* in Overall Population All-cause mortality and morbidity All-cause mortality 1.0 0.9 0.8 Placebo Event-free probability 0.7 13% risk reduction p= 0.009 0.6 0 3 6 9 12 15 18 21 24 27 Time since randomisation (months) Cohn et al. NEJM 2001;345:1667

  27. CHARM Program 3 component trials comparing Candesartan to placebo in patients with symptomatic heart failure CHARMAlternative CHARM Added CHARMPreserved n=2028 LVEF £40%ACE inhibitor intolerant n=2548 LVEF £40%ACE inhibitor treated n=3025 LVEF >40%ACE inhibitor treated/not treated

  28. CHARM ProgramMortality and morbidity CV Death or CHF Hospitalisation All Cause Mortality 0.77 Alternative p=0.0004 0.85 Added p=0.011 0.89 Preserved p=0.118 0.91 0.84 Overall p=0.055 p<0.0001 0.7 0.8 0.9 1.0 1.1 1.2 0.6 0.7 0.8 0.9 1.0 1.1 1.2 Hazard ratio Hazard ratio p heterogeneity=0.37 p heterogeneity=0.43

  29. ARB Indications in CHF • Patients intolerant to ACE-Inhibitors: (Class I recommendation in stage C) • On top of ACE I and B Blockers in patients who remain symptomatic: optional (discrepancy in guidelines): Class I (ESC, CCS), IIa (HFSA), and IIb (ACC/AHA) • Use of ARB instead of ACE-I is a Class IIa recommendation (reasonable, should be considered) in stage C heart failure

  30. 1.0 0.9 0.8 0.7 0.6 0.5 0 6 12 24 30 36 18 RALES NEJM 1999;341:709 Spironolactone Annual Mortality Aldactone 18%; Placebo 23% Survival Aldactone N = 1663 NYHA III-IV Mean follow-up 2 y p < 0.0001 Placebo months

  31. Spironolactone.Indications • Moderate-severe symptoms/advanced heart failure • Class I recommendation, level of evidence B • Routine combination of ACE-I, ARB and aldosterone antagonist is not recommended (Class III)

  32. Spironolactone. Practical use • Do not use if hyperkalemia, renal insuficieny • Monitor serum K+ at “frequent intervals” • Start ACE-i first • Start with 25 mg / 24h

  33. ß-Blockers • Has been traditionally contraindicated in pts with CHF • Now they are a corner stone in treatment of CHF

  34. ß-Adrenergic BlockersMechanism of action • Density of ß1 receptors • Inhibit cardiotoxicity of catecholamines • Neurohormonalactivation • HR • Anti-ischemic • Anti-hypertensive • Anti-arrhythmic

  35. ß-Adrenergic BlockersClinical Effects in CHF • Improve symptoms (only long term) • Reduce remodeling / progression • Reduce hospitalization • Reduce sudden death • Improve survival

  36. US Carvedilol HF NEJM 1996; 334: 1349-55 ß-Adrenergic Blockers 1.0 1.0 Carvedilol (n=696) 0.9 0.9 Survival % Placebo (n=398) p<0.001 0.8 0.8 0.7 0.7 Risk reduction = 65% I-II NYHA HF 0.6 0 50 100 150 200 250 300 350 400 Days

  37. CIBIS-II Lancet 1999;353:9 ß-Adrenergic Blockers 1 Bisoprolol 11.8% 0.9 0.8 P< 0.00005 Survival Placebo 17.3% 0.7 NYHA III-IV n=2647 0.6 Annual Mortality: bisoprolol=8.2%; placebo=12% Mean Follow-up 1.4 years 0.5 0 600 200 400 800 Days

  38. MERIT-HF Lancet 1999; 353: 2001 ß-Adrenergic Blockers Placebo 15 p=0.0062 Mortality % Metoprolol 10 5 Risk Reduction 34% NYHA II-IV N=3991 0 0 3 6 9 12 15 18 21 Months

  39. COPERNICUS NEJM 2001;344:1651 ß-Adrenergic Blockers 100 90 80 Survival% Carvedilol 70 p=0.00014 35% RR 60 Placebo N = 2289 III-IV NYHA 50 0 4 8 12 16 20 24 28 Months

  40. CAPRICORN Lancet 2001;357:1385 ß-Adrenergic Blockers 1 HR 0.77 (0.60 - 0.98) p<0.031 0.95 0.9 Carvedilol 116 / 975 (12%) Survival 0.85 0.8 Placebo 151 / 984 (15%) LVD / HF Post AMI 0.75 0.7 0 0.5 1 1.5 2 2.5 Years

  41. ß-Adrenergic BlockersIndications • Symptomatic heart failure (stage C) • Asymptomatic ventricular dysfunction - LVEF < 35 - 40 % (stage B) • After AMI Class I recommendation AHA / ACC HF guidelines 2005 ESC HF guidelines 2005

  42. ß-Adrenergic BlockersWhen to start ? • Patient stable • No physical evidence of fluid retention • No need for I.V. inotropic drugs • Start ACE-I / diuretic first • Start Low, Increase Slowly • Increase the dose every 2 - 4 weeks

  43. ß-Adrenergic BlockersDrugs and Dose (mg) Initial Target Bisoprolol 1.25 / 24h 10 / 24h Carvedilol 3.125 / 12h 25 / 12h Metoprolol succinnate12,5-25 / 24h 200 / 24h Nebivolol (ESC, elderly) 1.25/24h 10 mg/24h

  44. ß-Adrenergic BlockersAdverse Effects • Hypotension • Fluid retention / worsening heart failure • Fatigue • Bradycardia / heart block • Review treatment (+/-diuretics, other drugs) • Reduce dose • Consider cardiac pacing • Discontinue beta blocker only in severe cases

  45. Digitalis Glycosides • The role of digitalis has declined somewhat because of safety concern • Recent studies have shown that digitals does not affect mortality in CHF patients but causes significant • Reduction in hospitalization • Reduction in symptoms of HF

  46. 50 40 30 20 10 0 Digitalis DIG N Engl J Med 1997;336:525 Mortality % Placebo n=3403 p = 0.8 N=6800 NYHA II-III Digoxin n=3397 0 12 24 36 48 Months

  47. Digitalis. Indications • Sinus rythm: When no adequate response to ACE-i + diuretics + beta-blockers • Atrial Fibrillation: to slow AV conduction Dose 0.125 to 0.250 mg / day Narrow therapeutic to toxic ratio !!

  48. Other Drugs. (only in selected patients) • Inotropics: refractory HF • Nitrates: ischemia, angina, pulmonary congestion • Antiarrhythmics: (only amiodarone) H risk arrhyth. • Anticoagulants: High risk of embolism e.g Atrial Fibr. • Ca channel blockers (only amlodipine): ischemia, hypertension

  49. Devices • Cardiac Resynchronization Therapy (CRT) • Implantable Cardiac Defibrillator (ICD)

  50. Cardiac Resynchronization Therapy for Heart Failure (CRT) • Ventricular Dysynchrony • Electrical: Inter- or Intraventricular conduction delays typically manifested as left bundle branch block • Mechanical: Regional wall motion abnormalities compromising ventricular mechanics • Cardiac Resynchronization • Modification of interventricular, intraventricular, and atrio-ventricular activation sequences Tavazzi L. Eur Heart J 2000;21:1211-1214

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