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Bd1e Management Of Heart Failure

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Bd1e Management Of Heart Failure

  1. 1. Management of Chronic Heart Failure DR.SAMEER AMBAR DEPT OF CARDIOLOGY JNMC BELGAUM, INDIA [email_address]
  2. 4. <ul><li>Asses the functional class </li></ul><ul><li>BP <130/80 mm of Hg </li></ul><ul><li>Good glycaemic control </li></ul><ul><li>LIPIDS LDL < 100 (IHD) <70 (DM) </li></ul><ul><li>Avoid smoking, alcohol </li></ul><ul><li>Sodium restriction <2gms /day </li></ul><ul><li>Fluid restriction ,2 Litres/day </li></ul>
  3. 7. ACEI MECHANISM OF ACTION VASOCONSTRICTION VASODILATATION Kininogen Kallikrein Inactive Fragments Angiotensinogen Angiotensin I RENIN Kininase II Inhibitor ALDOSTERONE SYMPATHETIC VASOPRESSIN PROSTAGLANDINS tPA ANGIOTENSIN II BRADYKININ A.C.E.
  4. 10. <ul><li>SAVE ( NEJM 1992 327:669-677) </li></ul><ul><li>2231 pts EF<40%, 3-16d post MI , without sx of heart failure , </li></ul><ul><li>Up to 50 mg Captopril tid for 42 mo </li></ul><ul><li>AIRE (Lancet 1993:342:821) </li></ul><ul><li>2006 patients 3-10 days post MI with any evidence of post infarct clinical HF, </li></ul><ul><li>Up to 5 mg Ramipril bid for 15 mos </li></ul><ul><li>TRACE (NEJM 1995; 333: 1670-1676) </li></ul><ul><li>1749 pts 3-7 days post MI with EF<=35%, with or without symptomatic HF </li></ul><ul><li>trandolapril for 24-50 mos </li></ul>ACEI IN POST MI HF
  5. 11. <ul><li>Mortality </li></ul><ul><li>SAVE: 25% (placebo) vs 20% (captopril) - 19% RRR </li></ul><ul><li>AIRE: 23% (placebo) vs 17% (ramipril) - 27% RRR </li></ul><ul><li>TRACE: 42.3% (placebo) vs 34.7% (trandolapril)- 24% RRR </li></ul>
  6. 14. ARBs Clinical Study: <ul><li>1.Elite-II. Study: </li></ul><ul><li>Enrolled Target: CHF P’t </li></ul><ul><li>Drug: losartan v.s. captopril </li></ul><ul><li>Primary Endpoint:CHF Improvement </li></ul><ul><li>Result: losartan is not better than captopril </li></ul><ul><li>2.Va-HeFT Study: </li></ul><ul><li>Enrolled Target: CHF P’t </li></ul><ul><li>Drug: valsartan + Usual Group v.s. Usual Group </li></ul><ul><li>Primary Endpoint: CHF Event-Free Probability </li></ul><ul><li>Result: Reduce M/M by 13.3% </li></ul>
  7. 15. Granger CB, et al. Lancet . 2003;362:772-776. CHARM-Alternative Number at risk Candesartan 1,013 929 831 434 122 Placebo 1,015 887 798 427 126 0 1 2 3 Years 0 10 20 30 40 50 Placebo Candesartan HR 0.77 (95% CI 0.67-0.89), P =.0004 Adjusted HR 0.70, P <.0001 3.5 406 (40.0%) 334 (33.0%) Proportion With CV Death or CHF Hospitalization (%) Primary outcome of CV death or CHF hospitalization
  8. 16. 55% on BB
  9. 18. When to use Angiotensin receptor blockers <ul><li>1. There has been no definite mortality or morbility advantage of ARBs over ACE inhibitors demonstrated </li></ul><ul><li>2. Consider ARB in patient who is ACE inhibitor eligible if the patient is intolerant of ACE inhibitors because of cough, renal insufficiency, or hyperkalemia </li></ul>
  10. 19. When to use Angiotensin receptor blockers <ul><li>3. In the patient who is apparently ACE inhibitor intolerant, rule out other causes of presumed side effect: </li></ul><ul><li>a. Cough-evaluate for pulmonary edema </li></ul><ul><li>b. Hyperkalemia-concurrent potassium supplementation, potassium-sparing diuretic use </li></ul><ul><li>c. renal insufficiency-evaluate for prerenal azotemia, NSAID use </li></ul><ul><li>4. The incidence of cough and hyperkalemia is lower with ARBs versus ACE inhibitors </li></ul><ul><li>There does not appear to be a significant difference in incidence of renal insufficiency </li></ul>
  11. 21. Beta blockade in Heart failure <ul><li>Beta receptor levels in heart failure </li></ul><ul><ul><li>Normal Heart B1 80 : B2 20 </li></ul></ul><ul><ul><li>Severe Heart Failure B1 60 : B2 40 </li></ul></ul><ul><ul><ul><li>B1 receptors to selectively down-regulate secondary to high levels of catecholamine </li></ul></ul></ul><ul><ul><ul><li>B2 agonists retain full inotropic activity mediated through a B2 population that is not significantly decreased </li></ul></ul></ul>
  12. 23. Effect of Sympathetic Activation in Heart Failure <ul><li>CNS Sympathetic Outflow </li></ul><ul><li>Sympathetic activity to </li></ul><ul><li>kidneys & blood vessels </li></ul>Activation of RAS Vasoconstriction Sodium retention Disease Progression <ul><li>Cardiac sympathetic Activity </li></ul><ul><li>1 </li></ul><ul><li>Receptors </li></ul><ul><li>2 </li></ul><ul><li>Receptors </li></ul><ul><li>1 </li></ul><ul><li>Receptors </li></ul>Myocyte death Increased arrhythmias
  13. 25. Benefit Of Beta Blockers <ul><li>Improve symptoms and clinical status </li></ul><ul><li>Increase LV ejection fraction </li></ul><ul><li>Little effect on exercise tolerance </li></ul><ul><li>Reduce frequency of hospitalizations for heart failure </li></ul><ul><li>Decrease mortality </li></ul>
  14. 26. Action <ul><li>Time dependant improvement in LV remodelling </li></ul><ul><li>Reduce cetecholamine myocyte toxicity </li></ul><ul><li>Improved B1 signaling </li></ul><ul><li>Antiapoptosis </li></ul><ul><li>antiarrthymic </li></ul><ul><li>RAAS inhibition </li></ul>
  15. 27. Sympathetic Activation B1 Receptors B2 Receptors A1 Receptors Cardiotoxicity Carvedilol Metoprolol Propranolol
  16. 32. Clinical Trials <ul><li>Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise (PRECISE) </li></ul><ul><ul><li>278 patients with chronic stable symptomatic heart failure EF<35% despite diuretics and ACE </li></ul></ul><ul><ul><li>Carvedilol group was associated with greater improvement in NYHA Class </li></ul></ul><ul><ul><li>39% reduction in combined risk of death/hospitalization for any reason </li></ul></ul><ul><ul><li>46% reduction in risk of hospitalization for cardiovascular reason </li></ul></ul>Circulation 1996;94:2793-2799
  17. 33. Clinical Trials <ul><li>Merit-HF Trial( metaprolol randomised interventional trial in CHF) </li></ul><ul><ul><li>3991 patients with an ischemic or nonischemic cardiomyopathy (NYHA Class II or III) randomized to either Metoprolol XL up to 200mg/day or placebo. </li></ul></ul><ul><ul><li>Metoprolol XL was associated with a 35% reduction in mortality </li></ul></ul>Amer J Cardiol 1997;80:54J-58J
  18. 34. MERIT-HF METOPROL-XL: Mortality and Morbidity MERIT-HF Study Group. Lancet. 1999;353:2001-2007
  19. 35. <ul><li>NYHA III/IV </li></ul><ul><li>EF <0.25 </li></ul>Post-MI Patients with Severe Heart Failure (n= 384) Jánosi A et al, Am Heart J 2003;146:721-8 MERIT-HF
  20. 36. Total Mortality Months of follow-up Per cent 20 15 10 5 0 Placebo Metoprolol CR/XL p = 0.0004 Risk reduction = 40% 0 3 6 9 12 15 18 Jánosi A et al, Am Heart J 2003;146:721-8 MERIT-HF Post-MI Patients
  21. 37. Per cent 12 9 6 3 0 Risk reduction = 50% Sudden Death Placebo Metoprolol CR/XL p = 0.0004 0 3 6 9 12 15 18 Jánosi A et al, Am Heart J 2003;146:721-8 MERIT-HF Post-MI Patients Months of follow-up
  22. 38. Per cent 5 4 3 1 0 Risk reduction = 49% Death from Worsening Heart Failure Placebo Metoprolol CR/XL p = 0.021 2 0 3 6 9 12 15 18 Jánosi A et al, Am Heart J 2003;146:721-8 MERIT-HF Post-MI Patients Months of follow-up
  23. 39. Total Number of Hospitalizations Heart failure p=0.006 -32% All-cause ns -8% CV cause p=0.037 -17% MERIT-HF Post-MI Patients Jánosi A et al, Am Heart J 2003;146:721-8
  24. 40. Post-MI severe CHF Total mortality Cardiac death/nonfatal MI History of revasc. (PTCA or CABG) 40% 45% Risk reduction Events Plac/Beta 122/74 44/24 37/26 132/74 46/22 42/27 All Post-MI patients Post-MI severe CHF All Post-MI patients Relative risk and 95% CI 0.0 1.0 History of revasc. (PTCA or CABG) Jánosi A et al, Am Heart J 2003;146:721-8 MERIT-HF Post-MI Patients
  25. 41. Effect of metoprolol and placebo treatment on survival and hospitalization risk in class III and IV HF MERIT-HF Goldstein S et al. J Am Coll Cardiol 2001; 38(4):932-8 Endpoint Metoprolol (N) Placebo (N) Risk reduction (%) p value Total mortality 45 72 39% 0.0086 CV mortality 40 70 44% 0.0028 Sudden death 22 39 45% 0.024 Death from worsening HF 13 28 55% 0.015 Total hospitalizations 273 363 27% 0.0037 Total hospitalizations due to worsening HF 105 187 45% <0.0001
  26. 42. Comparison of findings in subanalysis and entire MERIT-HF cohort MERIT-HF Goldstein S et al. J Am Coll Cardiol 2001; 38(4):932-8 Endpoint Reductions in entire MERIT-HF cohort Reductions in class III and IV MERIT-HF subset Total mortality -34% -39% Sudden death -41% -45% Death due to worsening HF -49% -55%
  27. 43. <ul><li>40% reduction in Total Mortality </li></ul><ul><li>50% reduction in Sudden Death </li></ul><ul><li>32% reduction in number of hospitalizations for Worsening Heart Failure </li></ul>Jánosi A et al, Am Heart J 2003;146:721-8 MERIT-HF Post-MI Patients Mortality/Hospitalizations Summary
  28. 45. <ul><li>Enrolled 2289 patients with severe HF (LVEF <25%) </li></ul><ul><li>Randomized to carvedilol in a target dose of 25 mg bid for up to </li></ul><ul><li>29 months </li></ul>Carvedilol Prospective Randomized Cumulative Survival Trial (COPERNICUS) 35% reduction in the risk of all-cause mortality among patients with severe congestive heart failure (CHF) treated with carvedilol compared to placebo
  29. 46. COPERNICUS: Effect of carvedilol on the combined risk of morbidity and mortality Death or hospitalization for HF 0.000004 p value Endpoint COPERNICUS and CAPRICORN 0.00004 31% Death or hospitalization for a CV reason 0.76 Death or hospitalization for any reason Relative risk reduction 24% 0.00002 Odds ratio 27% 0.73 0.69
  30. 47. Beta Blockers Post MI LV dysfunction <ul><li>CAPRICORN( carvedilol post infarct survival control in LVD) </li></ul><ul><ul><li>1959 pts post MI LVEF<40% </li></ul></ul><ul><ul><li>Randomized to carvedilol or placebo </li></ul></ul><ul><ul><li>Results: </li></ul></ul><ul><ul><ul><li>Lower all cause mortality (12% vs. 15%) </li></ul></ul></ul><ul><ul><ul><li>Lower non-fatal MI </li></ul></ul></ul>Lancet 2001; 357: 1385–90
  31. 48. CAPRICORN All-Cause Mortality 0 0.5 1 1.5 2 2.5 Carvedilol n=975 Placebo n=984 Years Proportion Event-free <ul><li>23% </li></ul><ul><li>(2%, 40%) </li></ul>Risk reduction 0 0.90 0.70 0.60 0.80 The CAPRICORN Investigators. Lancet . 2001;357:1385-1390. Mortality Rates: Placebo 15%; Carvedilol 12% Carvedilol Post-Infarct Survival Control in LV Dysfunction 1.00
  32. 49. Clinical Use Of Beta Blockers <ul><li>Recommended for patients with NYHA class II-IV </li></ul><ul><li>General contraindications: </li></ul><ul><ul><li>Decompensated heart failure </li></ul></ul><ul><ul><li>Severe claudication </li></ul></ul><ul><ul><li>Bronchospasm </li></ul></ul><ul><ul><li>Advanced heart block </li></ul></ul><ul><ul><li>Use with caution if patient requires inotropes for support of circulatory function </li></ul></ul>
  33. 50. Beta-Blockade <ul><li>Cardiac Output </li></ul><ul><li>Renal </li></ul><ul><li>Blood Flow </li></ul>Sodium Retention Worsening Heart Failure
  34. 51. Considerations in selecting a beta-blocker <ul><li>Patients should be clinically stable and euvolemic before initiating beta-blocker therapy </li></ul><ul><li>Start at low doses and titrate upward gradually (doubling every 2-4 weeks) </li></ul><ul><li>Patients may experience an initial exacerbation of heart failure symptoms because of transient worsening of cardiac output </li></ul>
  35. 52. Clinical Use Cont . . . <ul><li>Clinical response may not be seen until 2 to 3 months after initiation of therapy </li></ul><ul><li>Abrupt withdrawal can lead to dramatic deterioration </li></ul><ul><li>Patient education paramount </li></ul>
  36. 53. Outcome in Post-MI Patients with Heart Failure CAPRICORN and MERIT-HF 1 Time to first event CAPRICORN All-cause mortality All-cause mortality/CV hosp. 1 MERIT-HF 23% 8% Risk reduction p- value p=0.03 Plac/Beta 151/116 122/74 40% p=0.0004 CAPRICORN MERIT-HF 367/340 326/258 ns 22% p=0.002 The CAPRICORN Investigators, Lancet 2001;357:1385-90 Jánosi A et al, Am Heart J 2003;146:721-8 Relative risk and 95% CI 0.0 1.0 Metoprolol CR/XL  1 Metoprolol CR/XL  1 Carvedilol  1  2 (  1 ) Carvedilol  1  2 (  1 )
  37. 54. LVEF: Change From Baseline Within Treatment-arm Comparison * P < 0.05; ** P < 0.01; *** P < 0.001 Enalapril Carvedilol & Enalapril Carvedilol -1 0 1 2 3 4 5  LVEF (%) *** *** *** *** *** ** * M6 M12 M18 M6 M18 M12 M6 M12 M18
  38. 55. Diuretics
  39. 57. Diuretics
  40. 59. RALES(randomised aldactone evaluation study) <ul><li>1663 patients Class 3-4 CHF, LVEF<35% on ACE-inhibitor/diuretic/dig </li></ul><ul><li>randomized to 25 mg spironolactone vs. placebo </li></ul><ul><li>issues: </li></ul><ul><ul><li>only 10% of patients on beta blockers </li></ul></ul>NEJM 1999:341:709-17
  41. 60. RALES <ul><li>Results: 46% mortality placebo vs 35% spironolactone (30% RRR) </li></ul><ul><li>adverse effects: </li></ul><ul><ul><li>10% of pts in spironolactone group developed gynecomastia. </li></ul></ul><ul><ul><li>-serious hyperkalemia (K>6) 14% vs 10% (not statist sig) </li></ul></ul>
  42. 61. EPHESUS(eplerenone post AMI HF efficacy and survival study) <ul><li>6642 patients: </li></ul><ul><li>a) 3-14 days post MI , </li></ul><ul><li>b) EF<40, </li></ul><ul><li>c) CHF (rales, pulm venous congestion seen on CXR, 3rd heart sound) OR Diabetes </li></ul><ul><li>randomized to 25 mg eplerenone titrated up to 50 mg po qd </li></ul>NEJM 2003;348:1309-21
  43. 62. <ul><li>Results: </li></ul><ul><ul><li>One year mortality: 15% risk reduction (11.8% vs 13.6%) </li></ul></ul><ul><ul><li>CV death or cardiovascular hospitalizations (26% vs 30.0%) </li></ul></ul><ul><li>(75% of patients on beta blockers) </li></ul><ul><li>adverse effects: </li></ul><ul><ul><li>serious hyperkalemia (K>6) Epler- 5.5% vs plac- 3.9% (p=.002) </li></ul></ul><ul><ul><li>serious hypokalemia (K<3.5) Epler- 8.4% plac- 13.1% (p<.001) </li></ul></ul><ul><ul><li>gynecomastia- 0.5% vs 0.6% </li></ul></ul>EPHESUS
  44. 63. Criteria for treatment with spironolactone <ul><li>New York heart Association class 3-4 </li></ul><ul><li>Left ventricular ejection fraction <35% </li></ul><ul><li>Serum creatinine <2.5 mg/dL </li></ul><ul><li>Serum potassium <5 mmol/L </li></ul><ul><li>Baseline treatment with ACE inhibitor (or other vasodilator if ACE inhibitor intolerance), loop diuretic, and digoxin as indicated </li></ul>
  45. 64. Digoxin <ul><li>Digoxin has a significant role in improving symptoms and rehospitalization rate </li></ul><ul><li>No impact on the total and cardiovascular mortality </li></ul><ul><li>Usually used only in severe CHF or in patients who remain symptomatic with optimal treatment </li></ul><ul><li>Digoxin is useful in CHF with atrial fibrillation </li></ul>
  46. 65. Digoxin <ul><li>DIG trial </li></ul><ul><li>6800 pts EF <45% </li></ul><ul><li>0.25 mg/day </li></ul><ul><li>22% reduction in hospitalisation </li></ul><ul><li>No mortlity benefit </li></ul><ul><li>28% RRR of death in post hoc analysis </li></ul>
  47. 67. Nesiritide <ul><li>Identical to human BNP </li></ul><ul><li>Causing vasodilation and decrease LV filling pressure </li></ul><ul><li>Decrease pulmonary capillary wedge pressure </li></ul><ul><li>Improves patients’ symptoms </li></ul><ul><li>Improvement in hemodynamics VMAC trial 5.8 mm of hg decrease on PCW </li></ul>
  48. 68. Nesiritide <ul><li>2 mcg/kg bolus infusion 0.01-0.03 mcg/kg/min for 3 hrs </li></ul><ul><li>Improved safety profile compared with dobutamine with fewer arrhythmias and better outcomes </li></ul><ul><li>It should not be used in patients who are overdiuresed, hypotensive, or present with other signs of inadequate perfusion - Worsening of renal failure (45%) </li></ul>
  49. 70. Inotropes <ul><li>Inotropes: direct adrenergic agonists, phosphodiesterase inhibitors, and dopaminergic agonists </li></ul><ul><li>Inotropes improve short term hemodynamics, they do not improve and in several cases may worsen long-term survival </li></ul><ul><li>Oral inotropic agents have resulted in excess mortality in patients with HF </li></ul>
  50. 71. Amiodarone <ul><li>Antiarrhythmic effect </li></ul><ul><li>Low dose amiodarone was safe and significantly reduced 2-year mortality (33.5% vs 41.4%, p=0.02) </li></ul><ul><li>in patients with moderate to severe HF (GESICA trial) </li></ul><ul><li>Another trial did not demonstrate mortality benefit, either all-cause or sudden death </li></ul>
  51. 72. Anticoagulation <ul><li>LVEF < 30% </li></ul><ul><li>LV thrombus </li></ul><ul><li>Atrial fibrillation </li></ul><ul><li>INR 2-3 </li></ul>
  52. 74. Thank you

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