The Problem Of Heart Failure

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  • Stages A through D reflect the progressive nature of cardiovascular disease into refractory end-stage heart failure. 1 These patient types, especially Stage A, B, and C patients, are commonly seen by primary care physicians. 1 Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2001;38:2101-2113.
  • Teaching Text According to ACTION-HF Guidelines, CAD is the cause of HF in about two thirds (or 66%) of patients with left ventricular systolic dysfunction. However, CAD is not the only etiological factor that matters in determining likely beta-blocker therapy candidates.
  • Slide 3 Patients with NYHA Class III and IV HF comprise the largest population of patients hospitalized with HF. These patients frequently require intravenous therapy once they have progressed to decompensated stages of HF.
  • The Kaplan Meier plot of death from any cause in the MERIT-HF trial showed that the benefit provided by metoprolol XL is seen very early, at approximately 3 months after initiation of treatment and increases over time. There was a statistically significant decrease in total mortality in the metoprolol XL group compared with placebo. Relative risk reduction was 34%.
  • β-BLOCKERS: USE IN HEART FAILURE IS NOW SUPPORTED BY OVERWHELMING EVIDENCE   The evidence supporting the use of β-blockade in heart failure is overwhelming. More than 15,000 patients have participated in clinical trials of β-blockade; the observed treatment effects have been both statistically significant and clinically impressive. Patients who received β-blockade demonstrated an improvement in cardiac function and symptoms. In addition, there was a highly significant decrease in all-cause mortality of 30% to 65% ( P <.0001). Further, the combined risk of death and hospitalization was reduced by a significant 35% to 40% ( P <.001). Notably, these benefits occur in patients who are already receiving an ACE inhibitor. 1 Lechat P, Packer M, Chalon S, et al. Clinical effects of β-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation . 1998;98:1184 – 1191.
  • Treatment of Heart Failure. Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival CONSENSUS. Prolonged administration of ACE-inhibitors reduces mortality in symptomatic heart failure. The first study to demonstrate this effect was CONSENSUS I. This graph shows the cumulative mortality curves of the treatment and placebo group in this randomized, double-blind trial. The study analyzed the effect of enalapril on prognosis of 253 patients with class IV heart failure, who also received digitalis, diuretics, and conventional vasodilators. At the end of 6 months of treatment, there was a clear-cut improvement in functional class, a reduction in the need for medications, and a 40% reduction in mortality (p<0.002). After 12 months the mortality reduction was 31% (p<0.001). Nonetheless, there were no differences in the incidence of sudden death between the two groups, or in the sub-group that received other conventional vasodilators. Another characteristic of this study was variability of the dose that was used for each patient (adjusted for tolerance and symptoms): 2.5-40mg/day. This aspect shows the importance of individualized treatment for heart failure patients. The CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429.
  • Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival SAVE (Survival and Ventricular Enlargement). Mortality curves in the SAVE study in patients with varying degrees of post-infarct ventricular dysfunction. In this study, 2231 patients with EF < 40% were randomized to receive captopril or placebo between 3 to 16 days after experiencing a transmural infarct. After 42 months, the captopril group had a significant reduction in overall mortality (-19%), number of reinfarctions (-25%), hospitalizations (-22%), and in the number of patients who developed clinical congestive heart failure. The mortality reduction appeared after 1 year of treatment. Pfeffer MA et al. Survival and Ventricular Enlargement (SAVE) Study. NEngl J Med 1992;327:669.
  • Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI) : Survival SOLVD study-symptomatic heart failure. Mortality curves in patients with clinical heart failure in the SOLVD treatment study. In this study, 2589 symptomatic heart failure patients with EFs<35% (90% in functional class II – III) were randomized to receive enalapril or placebo. Mortality over a 41 month follow-up period was 39.7% in the enalapril arm and 35.2% in the placebo arm (p<0.004). The mortality reduction was chiefly mediated through less progression of heart failure; deaths due to arrhythmia were not reduced. Additionally, the enalapril group required fewer hospitalizations for heart failure. The SOLVD Investigators. N Engl J Med 1991;325:293
  • ACE INHIBITORS: PROVEN TO REDUCE MORBIDITY AND MORTALITY   ACE inhibitors are central to the management of heart failure. Experience from large-scale clinical trials such as SOLVD Treatment, CONSENSUS, and V-HeFT II has shown that blocking the renin-angiotensin system (RAS) through ACE inhibition can reduce mortality. In data from a meta-analysis of these long-term, placebo-controlled trials with ACE inhibitors in heart failure, involving approximately 7,000 patients, the results were consistently positive. Overall, there was a 23% decrease in all-cause mortality, which was statistically significant ( P <.001) compared with the control groups. In addition, the combined risk of death or hospitalization was reduced by 35% ( P <.001). 1 Cardiac function improves, symptoms are relieved, and the clinical status improves in patients treated with ACE inhibitors. The effects on exercise tolerance, however, are equivocal. 1 Garg R, Yusuf S, for the Collaborative Group on ACE Inhibitor Trials. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA . 1995;273:1450–1456.
  • Slide The evidence based therapies for heart failure continue to be underutilized. This study analyzing heart failure care at 33 hospitals that participate in the University Hospital Consortium showed that many patients with heart failure due to systolic dysfunction are discharged home without initiation of therapies demonstrated to lower mortality rates. This so called treatment continues in the outpatient setting. Hospitalization for decompensated heart failure provides an opportunity to initiate the therapies that can halt the progression of heart failure. Studies on the strategy of in-hospital initiation of lipid lowering and other cardioprotective therapies, have demonstrated improved treatment rates, long-term patient compliance, and clinical outcomes. (Fonarow GC, Gawlinski A, Cardin S, Moughrabi S, Tillisch JI. Improved treatment of cardiovascular disease by implementation of a cardiac hospitalization atherosclerosis management program: CHAMP. Am J Cardiol 2001; 87:819-822.)
  • HF is severely undertreated and most patients do not receive optimal therapy.
  • Many patients with advanced systolic heart failure exhibit significant inter- or intraventricular conduction delays that disturb the synchronous beating of the left and right ventricles so that they pump less efficiently. This delayed ventricular activation and contraction is referred to as ventricular dysynchrony and is easily recognized by a wide QRS complex on an ECG. This IVCD (inter- or intraventricular conduction delay) typically has left bundle branch morphology.
  • The Problem Of Heart Failure

    1. 1. The Problem of Heart Failure Fathi Maklady . MD,FRCP Suez Canal University
    2. 2. Overview <ul><li>Epidemiology of heart failure </li></ul><ul><li>Highlights of the ACC/AHA guidelines </li></ul><ul><li>Overview of the clinical trials </li></ul>
    3. 8. A Public Health Crisis: Heart Failure Hospitalizations have Tripled in 25 Years NHLBI. Morbidity and Mortality: 2000 Chartbook on Cardiovascular, Lung, and Blood Diseases . Geneva: World Health Organization; 1996. Hospitalizations/100,000 Population 1970 1975 1980 1985 1990 1995 Year 65+ years 45-64 years 0 50 100 150 200 250
    4. 10. Prevalence of Heart Failure Worldwide 19,000 2.4 Japan 18,000 North America 14,000 5.3 Western Europe Rate (per million pop.) Absolute Numbers (millions of patients ) Murray CJL, Lopez AD. Global health statistics: a compendium of incidence, prevalence and mortality estimates for over 200 conditions . Geneva: World Health Organization;.
    5. 12. Hospitalization: The Major Factor in Heart Failure Costs in the US 60.6% Hospitalization $23.1 billion 38.6% Outpatient care $14.7 billion (3.4 visits/year /patient) 0.7% Transplants $270 million Total = $38.1 billion (5.4% of total health care costs) O’Connell JB, Bristow MR. J Heart Lung Transplant . 1994;13:S107-S112 .
    6. 13. Heart Failure <ul><li>A clinical syndrome in which the heart is </li></ul><ul><li>unable to pump sufficient blood to meet </li></ul><ul><li>the metabolic demands of the body. </li></ul>
    7. 14. DEFINITION <ul><li>“ HF is a complex clinical syndrome that </li></ul><ul><li>can result from any functional </li></ul><ul><li>or structural Cardiac disorder that impair </li></ul><ul><li>the ability of The ventricles to fill with </li></ul><ul><li>or eject blood” </li></ul><ul><li>ACC/AHA 2005 </li></ul>
    8. 17. Stages of Heart Failure <ul><ul><li>At Risk for Heart Failure: </li></ul></ul><ul><ul><li>STAGE A High risk for developing HF </li></ul></ul><ul><ul><li>STAGE B Asymptomatic LV dysfunction </li></ul></ul><ul><ul><li>Heart Failure: </li></ul></ul><ul><ul><li>STAGE C Past or current symptoms of HF </li></ul></ul><ul><ul><li>STAGE D End-stage HF </li></ul></ul>
    9. 18. New Approach to the Classification of Heart Failure Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. <ul><li>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) </li></ul>Refractory end-stage HF D <ul><li>Known structural heart disease </li></ul><ul><li>Shortness of breath and fatigue </li></ul><ul><li>Reduced exercise tolerance </li></ul>Symptomatic HF C <ul><li>Previous MI </li></ul><ul><li>LV systolic dysfunction </li></ul><ul><li>Asymptomatic valvular disease </li></ul>Asymptomatic HF B <ul><li>Hypertension obesity </li></ul><ul><li>CAD MTS </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Family history of cardiomyopathy </li></ul>High risk for developing heart failure (HF) A Patient Description Stage
    10. 19. ACC/AHA Staging System for HF -Marked symptoms at rest -Maximal medical therapy D: Refractory HF -Known structural Ht disease -SOB& Fatigue –reduced exercise tolerance C: Symptomatic HF -Previous MI -LVH -LVSD -Asymptomatic valvular Ht disease B: Asymptomatic HF -HTN -CAD -DM -Dyslipidaemia -FH of CM A: High risk for developing HF Patient description Stage
    11. 20. Stages of Heart Failure <ul><li>COMPLEMENT, DO NOT REPLACE NYHA CLASSES </li></ul><ul><li>NYHA Classes - shift back/forth in individual patient (in response to Rx and/or progression of disease) </li></ul><ul><li>Stages - progress in one direction due to cardiac remodeling </li></ul>
    12. 24. Systolic Heart Failure Diastolic Heart Failure
    13. 27. Neurohormonal System and HF <ul><li>There is substantial evidence that activation of neurohormonal system plays an important part in cardiac remodeling and thereby in the progression of HF : </li></ul><ul><li>- Nor epinephrine -Angiotensin11 </li></ul><ul><li>-Aldosteron -Endotheline </li></ul><ul><li>-vasopressin -Cytokines </li></ul>
    14. 28. The Progressive Development of Cardiovascular Disease Endstage Heart Disease Congestive Heart Failure Ventricular Dilation Remodeling Arrhythmia & Loss of Muscle Myocardial Infarction Myocardial Ischemia CAD Atherosclerosis Endothelial Dysfunction Risk Factors Coronary Thrombosis
    15. 29. Etiology and Clinical Characteristics of Heart Failure <ul><li>Coronary artery disease is the most common etiology of heart failure 1 </li></ul><ul><li>75% of CHF cases have antecedent hypertension 2 </li></ul><ul><li>Signs and symptoms of congestion (eg, rales, dyspnea, etc) are not always evident in HF patients </li></ul><ul><li>Most deaths occur suddenly and unexpectedly despite apparent clinical compensation 2 </li></ul>1 Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol . 1999;83(suppl 2A):1A–39A. 2 AHA. 2001 Heart and Stroke Statistical Update. 2000.
    16. 30. Assessment of patient with HF History <ul><li>- HTN Diabetes </li></ul><ul><li>-Dyslipidemia </li></ul><ul><li>Valvular heart disease </li></ul><ul><li>-CAD -PVD </li></ul><ul><li>-Myopathy RH fever </li></ul><ul><li>-Smoking -Obesity </li></ul><ul><li>-Alcohol -Pheo </li></ul><ul><li>-Thyroid disorder </li></ul><ul><li>Sexually transmitted D </li></ul><ul><li>Family History: </li></ul><ul><li>-MI -Stroke -PVD </li></ul><ul><li>-Sudden cardiac death </li></ul><ul><li>-Myopathy </li></ul><ul><li>-Cardiomyopathy </li></ul><ul><li>-Conduction defect </li></ul><ul><li>-Tachyarrhythmia </li></ul>
    17. 33. CHF Patient Population by NYHA Class Class I No limitations of physical activity Class II Slight limitations of physical activity Class III Marked limitations of physical activity Class IV Inability to carry out physical activities without discomfort and/or symptoms at rest Class II 1.68 M (35%) Class IV 240 K (5%) Class III 1.20 M (25%) Class I 1.68 M (35%) AHA Heart and Stroke Statistical Update 2001
    18. 34. Assessment of patient with HF <ul><li>Physical Examination </li></ul><ul><li>- Assessment of PT volume status, Orthostatic BP changes, WT,hight and BMI </li></ul><ul><li>-Exercise tolerance </li></ul>
    19. 35. Assessment of Patient with HF <ul><li>Laboratory Evaluation </li></ul><ul><li>-Complete BL picture -urine analysis </li></ul><ul><li>-Serum electrolytes:Ca ,,Mg,BUN,SC,LFTs, TSH </li></ul><ul><li>Glycohemoglobin,Lipid profile </li></ul><ul><li>12 lead ECG </li></ul><ul><li>2Dechocadiography </li></ul><ul><li>Coronary angio in PTs presenting with angina </li></ul>
    20. 36. Assessment of Patient with HF <ul><li>Value of Echocardiography: </li></ul><ul><li>The single most useful diagnostic test in evaluation of a PT with HF </li></ul>THE Value of Echocardiography The most useful diagnostic test in the evaluation of HF
    21. 37. Value of Echocardiography <ul><li>Three fundamental questions must be addressed: </li></ul><ul><li>1- Is the LVEF preserved or reduced ? </li></ul><ul><li>2-Is the structure of LV normal or abnormal ? </li></ul><ul><li>3-Are there other structural abnormality such as valvular,pericardial or RV that could account for the clinical presentation ? </li></ul>
    22. 43. Pathogenesis and Therapeutic Approaches <ul><li>LV Function </li></ul><ul><li>Cardiac Output </li></ul>Neurohormone Activation Progressive Heart Failure Diuretics Vasodilators ACE Inhibitors <ul><li>Imepdance </li></ul>Salt and Water Retention RAA System ANF Catecholamines ACE Inhibitor Digoxin { B-blockers
    23. 45. Targets for drug therapy <ul><li>* To improve symptoms </li></ul><ul><ul><li>Diuretics </li></ul></ul><ul><ul><li>Digoxin </li></ul></ul><ul><ul><li>ACE-inhibitors </li></ul></ul><ul><li>* To improve survival </li></ul><ul><ul><li>ACE-inhibitors </li></ul></ul><ul><ul><li> blockers </li></ul></ul><ul><ul><li>ARBs </li></ul></ul><ul><ul><li>Spironolactone </li></ul></ul>Davies et al. BMJ 2000; 320: 428-431
    24. 46. Stage A Therapy <ul><li>Recommended Therapies to Reduce Risk Include : </li></ul><ul><li>Treating known risk factors (hypertension, diabetes, etc.) </li></ul><ul><li>with therapy consistent with contemporary guidelines </li></ul><ul><li>Avoiding behaviors increasing risk (i.e., smoking </li></ul><ul><ul><li>excessive consumption of alcohol, illicit drug use) </li></ul></ul><ul><li>Periodic evaluation for signs and symptoms of HF </li></ul><ul><li>Ventricular rate control or sinus rhythm restoration </li></ul><ul><li>Noninvasive evaluation of LV function </li></ul><ul><li>Drug therapy – </li></ul><ul><ul><li>Angiotensin Converting Enzyme Inhibitors (ACEI) </li></ul></ul><ul><ul><li>Angiotensin Receptor Blockers (ARBs) </li></ul></ul>
    25. 47. Stage A Therapy <ul><ul><li>Routine use of nutritional supplements solely </li></ul></ul><ul><ul><li>to prevent the development of structural heart </li></ul></ul><ul><ul><li>disease should not be recommended for </li></ul></ul><ul><ul><li>patients at high risk for developing HF. </li></ul></ul>Therapies NOT Recommended
    26. 48. Stage B Patients with Asymptomatic LV Dysfunction
    27. 49. Stage B Therapy <ul><li>Recommended Therapies : </li></ul><ul><li>General Measures as advised for Stage A </li></ul><ul><li>Drug therapy for all patients </li></ul><ul><ul><li>ACEI or ARBs </li></ul></ul><ul><ul><li>Beta-Blockers </li></ul></ul><ul><li>ICDs in appropriate patients </li></ul><ul><li>Coronary revascularization in appropriate patients </li></ul><ul><li>Valve replacement or repair in appropriate patients </li></ul>
    28. 50. Stage C Patients with Past or Current Symptoms of Heart Failure
    29. 51. <ul><li>Recommended Therapies : </li></ul><ul><li>General measures as advised for Stages A and B </li></ul><ul><li>Drug therapy for all patients </li></ul><ul><ul><li>Diuretics for fluid retention </li></ul></ul><ul><ul><li>ACEI </li></ul></ul><ul><ul><li>Beta-blockers </li></ul></ul><ul><li>Drug therapy for selected patients </li></ul><ul><ul><li>Aldosterone Antagonists </li></ul></ul><ul><ul><li>ARBs </li></ul></ul><ul><ul><li>Digitalis </li></ul></ul><ul><ul><li>Hydralazine/nitrates </li></ul></ul><ul><li>ICDs in appropriate patients </li></ul><ul><li>Cardiac resynchronization in appropriate patients </li></ul><ul><li>Exercise Testing and Training </li></ul>Stage C Therapy (Reduced LVEF with Symptoms)
    30. 52. <ul><li>Recommended Therapies for Routine Use: </li></ul><ul><li>Treating known risk factor (hypertension) with therapy </li></ul><ul><li>consistent with contemporary guidelines </li></ul><ul><li>Ventricular rate control for all patients </li></ul><ul><li>Drugs for all patients - </li></ul><ul><ul><li>Diuretics </li></ul></ul><ul><li>Drugs for appropriate patients – </li></ul><ul><ul><li>ACEI </li></ul></ul><ul><ul><li>ARBs </li></ul></ul><ul><ul><li>Beta-Blockers </li></ul></ul><ul><ul><li>Digitalis </li></ul></ul><ul><li>Coronary revascularization in selected patients </li></ul><ul><li>Restoration/maintenance of sinus rhythm in </li></ul><ul><li>appropriate patients </li></ul>Stage C Therapy (Normal LVEF with Symptoms)
    31. 53. Calcium channel blocking drugs are not indicated as routine treatment for HF in patients with current or prior symptoms of HF and reduced LVEF. Hormonal therapies other than to replete deficiencies are not recommended and may be harmful to patients with current or prior symptoms of HF and reduced LVEF. Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patientswith current or prior symptoms of HF and reduced LVEF. Unproven/Not Recommended Drugs and Interventions Stage C Therapy (Reduced LVEF with Symptoms)
    32. 54. Long-term use of an infusion of a positive inotropic drug may be harmful and is not recommended for patients with current or prior symptoms of HF and reduced LVEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment (see recommendations for Stage D). Use of nutritional supplements as treatment for HF is not indicated in patients with current or prior symptoms of HF and reduced LVEF. Unproven/Not Recommended Drugs and Interventions Stage C Therapy (Reduced LVEF with Symptoms)
    33. 55. Unproven/Not Recommended Drugs and Interventions for HF <ul><li>Nutritional Supplements </li></ul><ul><li>Hormonal Therapies </li></ul><ul><li>Intermittent Intravenous </li></ul><ul><li>Positive Inotropic Therapy </li></ul>Stage C Therapy (Reduced LVEF with Symptoms)
    34. 56. Patients with LVEF less than or equal to 35%, sinus rhythm, and NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than 120 ms, should receive cardiac resynchronization therapy unless contraindicated. Cardiac Resynchronization Stage C Therapy (Reduced LVEF with Symptoms)
    35. 57. An ICD is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-MI, have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. Implantable Cardioverter- Defibrillators (ICDs) Stage C Therapy (Reduced LVEF with Symptoms)
    36. 58. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with nonischemic cardiomyopathy who have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. Placement of an ICD is reasonable in patients with LVEF of 30% to 35% of any origin with NYHA functional class II or III symptoms who are taking chronic optimal medical therapy and who have reasonable expectation of survival with good functional status of more than 1 year. ICDs (cont’d) Stage C Therapy (Reduced LVEF with Symptoms) I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
    37. 59. Stage D Patients with Refractory End-Stage HF
    38. 60. Stage D Therapy <ul><li>Recommended Therapies Include: </li></ul><ul><li>Control of fluid retention </li></ul><ul><li>Referral to a HF program for appropriate pts </li></ul><ul><li>Discussion of options for end-of-life care </li></ul><ul><li>Informing re: option to inactivate defibrillator </li></ul><ul><li>Device use in appropriate patients </li></ul><ul><li>Surgical therapy – </li></ul><ul><ul><li>Cardiac transplantation </li></ul></ul><ul><ul><li>Mitral valve repair or replacement </li></ul></ul><ul><ul><li>Other </li></ul></ul><ul><li>Drug Therapy – </li></ul><ul><ul><li>Positive inotrope infusion as palliation </li></ul></ul><ul><ul><li>in appropriate patients </li></ul></ul>
    39. 61. Stage D Therapy Continuous intravenous infusion of a positive inotropic agent may be considered for palliation of symptoms in patients with refractory end-stage HF. Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF. Medical Therapy
    40. 62. Stage D Therapy Referral for cardiac transplantation in potentially eligible patients is recommended for patients with refractory end-stage HF. The effectiveness of mitral valve repair or replacement is not established for severe secondary mitral regurgitation in refractory end-stage HF. Surgical Therapy I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
    41. 63. Stage D Therapy Consideration of an LV assist device as permanentor “destination” therapy is reasonable in highly selected patients with refractory end-stage HF and an estimated 1-year mortality over 50% with medical therapy. Pulmonary artery catheter placement may be reasonable to guide therapy in patients with refractory end-stage HF and persistently severe symptoms. Device Use I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B
    42. 64. Stage D Therapy Partial left ventriculectomy is not recommended inpatients with nonischemic cardiomyopathy and refractory end-stage HF. Routine intermittent infusions of positive inotropic agents are not recommended for patients with refractory end-stage HF. Therapies NOT Recommended
    43. 65. DIURETICS
    44. 69. CHF THERAPY ACE-Inhibitors B-blockers
    45. 70. Beta Blockers
    46. 71. B-Blockers in CHF Historical Perspective <ul><li>1975- 1980 First reports of clinical benefit* </li></ul><ul><li>High NE associated with high mortality </li></ul><ul><li>B receptor down-regulation </li></ul><ul><li>?Are B-Adrenergic-blocking agents useful in the treatment of DCM** </li></ul>* Waagstein Br Heart Journal 1975, Swedberg Br Heart Journal 1980 **Alderman Grossman Circulation 1985
    47. 75. What is the evidence
    48. 76. Effect of Carvedilol on Disease Progression in Mild or Moderate Heart Failure *Disease progression was defined as HF death or hospitalization or the need for sustained increase in medications for HF. Patients were on a background of diuretics, ACE inhibitors, ± digoxin. Colucci WS et al. Circulation . 1996;94:2800–2806. Probability of event-free survival  1.0 0.8 0.6 0 50 100 150 200 250 300 350 400 Carvedilol (n=232) Placebo (n=134) P =.008 R isk reduction 48% Days 0
    49. 78. Total Mortality Percent of patients Months of follow-up 0 3 6 9 12 15 18 21 20 15 5 0 10 P =0.0062 Risk reduction: 34% Placebo n=2001 Metoprolol XL n=1990
    50. 80. Key Findings from CIBIS11 <ul><li>All cause mortality reduced by 34% </li></ul><ul><li>Sudden Death reduced by 44% </li></ul><ul><li>Fewer hospitalization with bisoprolol </li></ul><ul><li>Significant fewer CVdeath </li></ul><ul><li>% of permanent treatment withdrawal was identical in both groups </li></ul>
    51. 81. ß-Blockers: Use in Heart Failure is Now Supported by Overwhelming Evidence <ul><li>> 15,000 patients evaluated in long-term placebo-controlled clinical trials </li></ul><ul><li>Improvement in cardiac function and symptoms; equivocal effects on exercise tolerance </li></ul><ul><li>Decrease in all-cause mortality by 30%–65% ( P <.0001) </li></ul><ul><li>Decrease in combined risk of death and hospitalization by 35% – 40% ( P <.001) </li></ul><ul><li>Effect shown in patients already receiving ACE inhibitors </li></ul>
    52. 82. B-Blockers in CHF <ul><li>Are B-Blockers Effective in CHF? </li></ul><ul><li>Is it a class effect? </li></ul><ul><li>Is it safe to use in advanced CHF (FTC IV)? </li></ul><ul><li>When should you initiate B-blockers? </li></ul><ul><li>Are B-blockers safe to use post MI & CHF? </li></ul>- Efficacy seen with Bisoprolol, Metoprolol XL, Carvedilol - Efficacy and safety established with Carvedilol - May be started in the hospital when euvolemic (IMPACT-HF ) - May be initiated post MI with CHF/LV dysfunction (CAPRICORN) -Yes
    53. 83. ACE - I
    54. 84. Aldosterone Sympathetic activation Growth factor stimulation NA + retention H 2 O retention K + excretion Mg + excretion Vascular smooth muscle constriction Angiotensin converting enzyme (ACE) Angiotensin II Liver secretes angiotensinogen Kidneys secrete renin The Renin-Angiotensin-Aldosterone (RAA) System Angiotensinogen Angiotensin I Adrenal cortex secretes aldosterone Blood Renin Pro- Inflamm tory Apoptosis
    55. 85. Angiotensin I Angiotensinogen (Liver) Angiotensin II ACE-inhibitor ARBs AT 1 receptor blocker Bradykinin Peptides Chymase Pathways of Ang II generation de Gasparo et al. Pharmacol Rev. 2000; 52: 415 Bad Good X X X AT 1 AT 2
    56. 86. Effect of ACE Inhibitors on Mortality Reduction in Patients With CHF Trial ACEI Controls RR (95% CI) CONSENSUS I SOLVD (Treatment ) SOLVD (Prevention) Chronic CHF Post MI SAVE TRACE AIRE 39% 54% 0.56 (0.34–0.91) 40% 35% 0.82 (0.70–0.97) 15% 16% 0.92 (0.79–1.08) 25% 20% 0.81 (0.68–0.97) 17% 23% 0.73 (0.60–0.89) SMILE 6.5% 8.3% 0.78 (0.52–1.12) Average 0.78 (0.67–0.91) 35% 42% 21% 25% Mortality Garg R et al. JAMA. 1995;273:1450–1456. Data shown from individual trials–not direct comparison data.
    57. 87. Placebo Enalapril 12 11 10 9 8 7 6 5 PROBABILITY OF DEATH MONTHS 0.1 0.8 0 0.2 0.3 0.7 0.4 0.5 0.6 p< 0.001 CONSENSUS 4 3 2 1 0 N Engl J Med 1987;316:1429 30% risk reduction
    58. 88. Mortality % N Engl J Med 1992;327:669 SAVE 20% risk reduction P<0.019 4 Years 30 20 10 0 1 2 3 Placebo Captopril 0 n=1115 n=1116 Asymptomatic ventricular dysfunction post MI
    59. 89. Months 0 6 12 p = 0.0036 % MORTALITY 24 18 30 36 42 48 Enalapril n=1285 Placebo n=1284 N Engl J M 1991;325:293 SOLVD (Treatment) 16% risk reduction 50 40 30 20 10 0
    60. 90. ACE Inhibitors: Proven to Reduce Morbidity and Mortality <ul><li> 7000 patients evaluated in long-term placebo-controlled clinical trials </li></ul><ul><li>Improvements in cardiac function, symptoms, and clinical status; equivocal effects on exercise tolerance </li></ul><ul><li> all-cause mortality by 23% ( P <.001) and  combined risk of death and hospitalization by 35% ( P <.001) </li></ul><ul><ul><li>Effect shown in SOLVD Treatment, CONSENSUS, and V-HeFT II trials </li></ul></ul>Garg R, Yusuf S. JAMA . 1995;273:1450–1456.
    61. 91. ACE Inhibition in Heart Failure <ul><li>All patients with heart failure due to left ventricular systolic dysfunction should receive an ACE inhibitor unless they have a contraindication to its use or cannot tolerate treatment with the drug. </li></ul><ul><li>Treatment with an ACE inhibitor should not be delayed until the patient is found to be resistant to treatment with other drugs. </li></ul>Consensus Recommendations Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol . 1999;83(suppl 2A):1A–39A.
    62. 92. Patients Not Receiving ACE-Is Possible underuse Contraindication Other AEs Cough 73% 27% 22% 20% 33% 25% 167 Cardiology and 250 Internal Medicine Clinics, Feb 14-25, 2000. Data from TEMISTOCLE Registry, ANMCO. N = 2127
    63. 93. Utilization of Evidence Based Therapies in Heart Failure ACE Inhibitors Beta Blockers 0 20 40 60 80 100 Percent of Patients 29 19 69 University Hospital Consortium HF Registry: 33 Centers, 1239 patients, Year 2000 Discharge Medications Spironolactone
    64. 94. Under treatment of HF in Europe Diuretics ACE-inhibitor  blocker Digitalis glycoside Nitrate Spironolactone ARB 0 20 40 60 80 100 Percent of patients receiving agent Cardiovascular drug use Cleland et al. Eur Heart J. 2001; 22: 494
    65. 95. ARBs
    66. 96. What is the Potential Role of ARBs in Patients With Congestive Heart Failure (CHF)? <ul><li>Are ARBs more efficacious than angiotensin-converting enzyme inhibitors (ACE-Is)? </li></ul><ul><li>Are ARBs as efficacious as ACE-Is? </li></ul><ul><li>Is the combination of an ARB and an ACE-I more efficacious than ACE-I monotherapy? </li></ul><ul><li>Are ARBs efficacious in patients who cannot tolerate ACE-Is? </li></ul><ul><li>Are ARBs efficacious in patients with heart failure and preserved left ventricular function? </li></ul>
    67. 97. Additional Benefits of ARB and ACE-I Combination Therapy <ul><li>Neurohormonal profile 1 </li></ul><ul><li>Prevention of left ventricular remodeling 1 </li></ul><ul><li>Hemodynamics 2 </li></ul><ul><li>Exercise capacity 3 </li></ul>However, only large-scale randomized controlled trials can prove reduction of morbidity and mortality in heart failure 1 RESOLVD. Circulation. 1999;100:1056-1064. 2 Baruch L et al. Circulation. 1999;99:2658-2664. 3 Hamroff G et al. Circulation. 1999;99:990-992.
    68. 98. New Therapies <ul><li>Biventricular pacing-LV pacing via the coronary sinus </li></ul><ul><li>TNF-alpha blockers- for Class III-IV CHF </li></ul><ul><li>Endothelin blockers </li></ul><ul><li>Neutral endopeptidase blockers </li></ul><ul><li>Vasopressin </li></ul>
    69. 99. Biventricular Pacing Ventricular Dysynchrony <ul><li>Abnormal ventricular conduction resulting in a mechanical delay </li></ul><ul><ul><li>Wide QRS (IVCD); typically LBBB morphology </li></ul></ul><ul><ul><li>Poor systolic function </li></ul></ul><ul><ul><li>Impaired diastolic function </li></ul></ul>ECG depicting interventricular conduction delay
    70. 104. Heart Failure in Conclusion <ul><li>Confirm the clinical diagnosis with an echocardiogram </li></ul><ul><ul><li>?new role for BNP </li></ul></ul><ul><li>Determine the etiology and reverse it, if possible (Rx for HTN, stop alcohol, reverse or treat ischemia, control HR in AF) </li></ul>
    71. 105. Heart Failure in -Conclusion <ul><li>Control BP </li></ul><ul><ul><li>May add Hydralazine/Isosorbide (VeHFT Trial) </li></ul></ul><ul><ul><li>Avoid CCB, except for Amlodipine, Felodipine </li></ul></ul><ul><li>May add Digoxin in symptomatic pts, or Afib </li></ul><ul><li>AVOID </li></ul><ul><ul><li>ASA (in non-ischemia DCM) & NSAIA </li></ul></ul><ul><ul><li>Coumadin (unless Afib) </li></ul></ul><ul><li>Multidiscipline Approach emphasizing CARE MANAGEMENT </li></ul><ul><ul><li>Move away from Episodic Care </li></ul></ul>
    72. 106. Heart Failure-Conclusion <ul><li>Add Diuretic if neck veins remain elevated (Block secondary effects of RAA System) </li></ul><ul><ul><li>Attempt euvolemic status </li></ul></ul><ul><ul><li>Add Aldactone in FTC III-IV pts (RALES) </li></ul></ul><ul><ul><li>?Eplerenone in post MI (EPHESUS) </li></ul></ul><ul><li>Add ACEI Therapy (Block RAA System) </li></ul><ul><ul><li>May use ARB if ACE intolerant (ELITE II, ValHFT, CHARM, VALIANT) </li></ul></ul><ul><li>Add Beta Blockers to lower HR to about 60 beats per minute </li></ul><ul><ul><li>Metoprolol, Carvedilol , Bisoprolol </li></ul></ul>
    73. 108. THANK YOU

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