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Heart Failure

Heart Failure. Liviu Klein MD, MS http://www.cardiologyfellows.northwestern.edu/cculectures. Outline. Definition. Definition Pathophysiology Epidemiology (prevalence, incidence, trends) Epidemiology (mortality and associated morbidity) Risk factors Heart failure stages and treatment

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Heart Failure

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  1. Heart Failure Liviu Klein MD, MS http://www.cardiologyfellows.northwestern.edu/cculectures

  2. Outline Definition • Definition • Pathophysiology • Epidemiology (prevalence, incidence, trends) • Epidemiology (mortality and associated morbidity) • Risk factors • Heart failure stages and treatment • Advanced heart failure and transplant

  3. Heart Failure Definition • A complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. • Cardinal manifestations are dyspnea and fatigue (which may limit exercise tolerance), and fluid retention (which may lead to pulmonary congestion and peripheral edema). • Both abnormalities can impair the functional capacity and quality of life of affected individuals, but they do not necessarily dominate the clinical picture at the same time. Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  4. Heart Failure Definition • Some patients have exercise intolerance but little evidence of fluid retention, whereas others complain primarily of edema and report few symptoms of dyspnea or fatigue. • Because not all patients have volume overload at the time of initial or subsequent evaluation, the term “heart failure” is preferred over the older term “congestive heart failure.” • One line definition: LV EDP > 12 mmHg Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  5. Outline Pathophysiology • Definition • Pathophysiology • Epidemiology (prevalence, incidence, trends) • Epidemiology (mortality and associated morbidity) • Risk factors • Heart failure stages and treatment • Advanced heart failure and transplant

  6. Heart Failure Pathophysiology Cardiac injury Increased load Reduced systemic perfusion Activation of RAS, SNS, and cytokines Altered gene expression Growth and remodeling Ischemia and energy depletion Direct toxicity Apoptosis Necrosis Cell death

  7. PathologicRemodeling Low ejectionfraction Left ventricularinjury Progression of Heart Failure Coronary artery disease Cardiomyopathic factors Atrial Fibrillation Valvular disease Hypertension Diabetes Death

  8. NORMAL No symptoms Normal exercise Normal LV fxn Asymptomatic LV Dysfunction No symptoms Normal exercise Abnormal LV fxn Compensated No symptoms Exercise Abnormal LV fxn Decompensated Symptoms Exercise Abnormal LV fxn Refractory Symptoms not controlled with treatment Heart Failure Clinical Stages

  9. Outline • Definition • Pathophysiology • Epidemiology (prevalence, incidence, trends) • Epidemiology (mortality and associated morbidity) • Risk factors • Heart failure stages and treatment • Advanced heart failure and transplant Epidemiology (prevalence, incidence, trends)

  10. Prevalence of Heart Failure Source: CDC/NCHS and NHLBI.

  11. Prevalence of Heart Failure Murray CJL, Lopez AD. Global health statistics: a compendium of incidence, prevalence and mortality estimates for over 200 conditions. Geneva: World Health Organization; 1996.

  12. Sys/Diastolic Dysfunction Prevalence Redfield MM et al. JAMA. 2003; 289: 194-202.

  13. Systolic Dysfunction Prevalence Wang TJ et al. Ann Intern Med. 2003; 138: 907-916. 4%

  14. Temporal Changes in Incidence Roger VL et al. JAMA. 2004; 292: 344-351.

  15. Outline • Definition • Pathophysiology • Epidemiology (prevalence, incidence, trends) • Epidemiology (mortality and associated morbidity) • Risk factors • Heart failure stages and treatment • Advanced heart failure and transplant Epidemiology (mortality and associated morbidity)

  16. Cardiovascular Deaths 300,000 death/yr

  17. Placebo 100 Conventional therapies (diuretics, digoxin) 90 NYHA Class IV (CONSENSUS) 80 70 60 NYHA Class II–III(SOLVD Treatment Trial) 50 Mortality (%) 40 30 20 10 0 0 6 12 18 24 30 36 42 48 Months Survival according to NYHA Class NYHA Class I–II(SOLVD Prevention Trial) CONSENUS Trial Study Group. N Engl J Med. 1987; 316: 1429-1435. The SOLVD Investigators. N Engl J Med. 1991; 325: 293-298. The SOLVD Investigators. N Engl J Med. 1992; 327: 685-690.

  18. Trends in Heart Failure Mortality Roger VL et al. JAMA. 2004; 292: 344-351.

  19. Mode of Death by NYHA Class NYHA IV NYHA II NYHA III Other 15% Other 11% Other 24% SD 33% SD 64% SD 59% HF 26% HF 12% HF 56% MERIT-HF Study Group. Lancet. 1999; 353: 2001-2007.

  20. Heart Failure Hospitalizations Source: CDC/NCHS.

  21. Heart Failure Hospitalizations 250 200 150 100 50 0 1 mil hospitalizations/ year 65+ years Hospitalizations/100,000 Population 45-64 years 1975 1980 1985 1990 1995 1970 Year Rosamond W et al. Circulation. 2008; 115: e2-e122.

  22. Estimated Direct and Indirect Costs Rosamond W et al. Circulation. 2008; 115: e2-e122.

  23. Physicians/Other Providers ($2 billion) 7% Drugs/Medical Durables ($3 billion) 10% Hospital/Nursing Home ($21 billion) 73% Home Health ($3.0 billion) 10% Total Expenditure (direct costs) = $29 billion Heart Failure Direct Costs Rosamond W et al. Circulation. 2008; 115: e2-e122.

  24. Outline • Definition • Pathophysiology • Epidemiology (prevalence, incidence, trends) • Epidemiology (mortality and associated morbidity) • Risk factors • Heart failure stages and treatment • Advanced heart failure and transplant Risk factors

  25. Outline • Definition • Pathophysiology • Epidemiology (prevalence, incidence, trends) • Epidemiology (mortality and associated morbidity) • Risk factors • Heart failure stages and treatment • Advanced heart failure and transplant Heart failure stages and treatment

  26. Stage Patient Description A High risk for developing heart failure (HF) • Hypertension • CAD • Diabetes mellitus • Family history of cardiomyopathy B Asymptomatic HF • Previous MI • LV systolic dysfunction • Asymptomatic valvular disease C Symptomatic HF • Known structural heart disease • Shortness of breath and fatigue • Reduced exercise tolerance D Refractory end-stage HF • Marked symptoms at rest despite maximal medical therapy (eg, those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions) New Classification of Heart Failure Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  27. Management of Chronic HF • Establish diagnosis (BNP, echo) • Determine etiology • Define syndrome (e.g. systolic vs. diastolic) • Correct precipitating factors (NSAIDS, COX2, etc.) • Evaluate and correct ischemia • Initiate chronic therapy • Nonpharmacologic (e.g. exercise, tx. of sleep apnea, etc) • Pharmacologic (ACE - I, b - Blockers, ARB, diuretics, digoxin, etc.) • Electrical • Surgical • Assess response to therapy

  28. Stage C: Symptomatic HF Class I • Level A evidence • Diuretics in patients with fluid retention • ACE inhibition, unless contraindicated • Beta blockade in stable patients, unless contraindicated • Digitalis, unless contraindicated • Level B evidence • Withdrawal of drugs known to adversely affect the clinical status of patients All Class I recommendations for Stages A and B Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  29. Diuretics • Loop diuretics in pts. with CrCl < 30 • Torsemide ↓ hospitalizations compared to furosemide • Have to be given bid to avoid rebound Na reabsorbtion • May use thiazides if CrCl > 30 • Use combination (e.g. furosemide + thiazide), iv bolus or iv drips • Metolazone in refractory HF or in pts. with renal failure. Should not be used daily. • Add spironolactone if Cr < 2.5 and K < 5. Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  30. ACE - I and Mortality in HF Mortality Trial ACEI Placebo RR (95% CI) Drug (mean dose) Chronic HF CONSENSUS I 39% 54% 0.56 (0.34-0.91) Enalapril (18.4 mg) SOLVD (T) 35% 40% 0.82 (0.70-0.97) Enalapril (11.2 mg) SOLVD (P) 15% 16% 0.92 (0.79-1.08) Enalapril (12.7 mg) Post-MI SAVE 20% 25% 0.81 (0.68-0.97) Captopril (150 mg)* AIRE 17% 23% 0.73 (0.60-0.89) Ramipril (1.25-5 mg)† TRACE 35% 42% 0.78 (0.67-0.91) Trandolapril (1-4 mg)† Zofenopril (7.5-30 mg)† SMILE 5% 6.5% 0.75 (0.40-1.11) 0.84 Totals 21% 25% * No mean given; target dose † No mean given; dose range

  31. ACE Inhibitors • Most pts. tolerate ACE - I. • ACE - I improve symptoms immediately (days). • Pts. should not be “too dry” (no orthostatic ↓BP). • If ↓ BP, check for orthostatic changes. If none, ACE - I OK. • Low BP and CRF are not CI for ACE - I. • If BUN/ Cr are raising, adjust the diuretic dose. • Low BP, low Na, renal dysfunction: low dose, short acting ACE - I, titrate to target dose or the highest dose tolerated. • Low vs. high dose ACE - I: difference in outcomes. Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  32. Beta - Blockers in HF Study All - cause All - cause mortality hospitalizations CIBIS II 1 (bisoprolol) ß 34% ß 20% 2647 pts. NYHA III - IV (p < 0.0001) (p = 0.0006) MERIT – HF 2 (metoprolol XL) ß 34% ß 8.6% 3991 pts. NYHA II - IV (p = 0.0062) (p = 0.005) COPERNICUS 3 (carvedilol) ß 35% ß15% 2289 pts. NYHA IV (p = 0.0014) (p = 0.0029) 1 CIBIS II Investigators and Committees. Lancet. 1999; 353: 9-17. 2 MERIT - HF Study Group. Lancet. 1999; 353: 2001-2007. 3 Packer M et al. N Engl J Med. 2001; 344: 1651-1658.

  33. Beta-Blockers: Not Created Equal Study All - cause All - cause mortality hospitalizations BEST1 (bucindolol) ß 10% ß 8% 2708 pts. NYHA III - IV (p < 0.1) (p = 0.08) SENIORS2 (nebivolol) ß 12% ß 4%* 2135 pts. NYHA II - III (p = 0.21) (p = 0.47) 1 BEST Investigators. N Engl J Med. 2001; 344: 1659-1667. * All-cause mortality/ CV hospitalizations 2 Flather MD et al.Eur Heart J . 2005; 26: 215-221.

  34. Beta-Blockers: Not Created Equal ?

  35. 40 Metoprolol IR 50 mg bid 30 Carvedilol 25 mg bid Mortality (%) 20 HR 0.83 (0.74 - 0.93) p = 0.0017 10 0 0 1 2 3 4 5 Time (years) COMET: Metoprolol vs. Carvedilol Poole-Wilson PA et al. Lancet. 2003; 362: 7-16.

  36. Beta - Blockers • Only bisoprolol, carvedilol and metoprolol succinate. • Start at low doses, increase every 2 weeks to target dose or the highest tolerated dose. • Intermediate vs. high dose: no difference in outcomes. • Do not start in pts. dependent of inotropic support. • Can start before hospital discharge in pts. not fluid overloaded. • Do not stop BB in hospitalized pts. who are on chronic BB therapy (may worsen HF). • BB will take 3-6 months to improve symptoms. • Low BP and severe HF are not CI for BB. Hunt SA et al. J Am Coll Cardiol. 2005; 46: e1-e86.

  37. 0.40 Standard Therapy Metoprolol p < 0.0001 0.35 p = 0.013 for metoprolol vs. standard therapy Ejection Fraction 0.30 p < 0.05 0.25 0.20 Baseline Day 1 1 Mo 3 Mo Day 1 1 Mo 3 Mo Baseline Time Course of Changes in LV EF Hall SA et al. J Am Coll Cardiol. 1995; 25: 1154-1160.

  38. All-cause mortality Death/Hospitalization Which First: ACE or BB? Willenheimer R et al. Circulation.. 2005; 112: 2426-2430.

  39. SCD/All-cause Mortality with First Bisoprolol Compared with Enalapril Willenheimer R. World Congress of Cardiology 2006; September 6, 2006; Barcelona, Spain.

  40. Beta - Blockers

  41. Angiotensin Receptor Blockers • Combination ARB + ACE - I + Beta - Blockers is safe. • No mortality benefit when ARB is added to ACE - I. • ARB are useful in pts. who are ACE intolerant. • ARB could be added to ACE - I for symptomatic improvement. • Triple RAAS blockade (ACE - I, ARB, aldosterone blockers) should not be used (Hyper K).

  42. CHARM Program 3 component trials comparing candesartan to placebo in patients with symptomatic HF CHARM-Alternative CHARM- Added CHARM-Preserved n=2028 LVEF < 40%ACE inhibitor intolerant n=2548 LVEF < 40%ACE inhibitor treated n=3025 LVEF > 40%ACE inhibitor treated/not treated Primary outcome for each trial: CV death or HF hospitalization Primary outcome for overall program: All-cause death Pfeffer MA et al. Lancet. 2003; 362: 759-767.

  43. Cardiovascular death/HF hospitalizations All-cause mortality Alternative Added Preserved Overall 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 Effect of Candesartan on Mortality and HF Hospitalizations Pfeffer MA et al. Lancet. 2003; 362: 759-767.

  44. 1.00 30% Relative risk reduction 0.95 0.90 0.85 0.80 0.75 Mortality Spironolactone 0.70 0.65 0.60 p< 0.001 0.55 Placebo 0.50 0.45 0.00 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Aldosterone Antagonists: Spironolactone Pitt B et al. N Engl J Med. 1999; 341; 709-715.

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