RECENT ADVANCES TACOMA CARDIOLOGY CONFERENCE 14 OCTOBER in HEART FAILURE: Drugs, Devices, and Diastolic Dysfunction TOBIAS LEE, MD

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1 RECENT ADVANCES in HEART FAILURE: Drugs, Devices, and Diastolic Dysfunction TOBIAS LEE, M.D. TACOMA CARDIOLOGY CONFERENCE 14 OCTOBER 2006

2 GOALS OF DISCUSSION Quick Review of Heart Failure. Update on Drug Management. Update on Device Management. Focus on Diastolic Dysfunction. No conflicts of interest. Tree on a Hill by Tobias Lee

3 ACC/AHA DEFINITION D OF HEART FAILURE Heart failure is 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. The cardinal manifestations of heart failure are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary congestion and peripheral edema. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

4 DIFFERENTIAL DIAGNOSIS Myocardial ischemia Pulmonary disease Pneumonia Asthma COPD Pulmonary embolus Pulmonary hypertension Sleep-disordered breathing Obesity Deconditioning Malnutrition Anemia Depression Renal failure Hepatic failure Hypoalbuminemia Venous stasis Flowers, Grand Teton by Tobias Lee Anxiety & hyperventilation syndrome Adams KF, J Lindenfeld et al Heart failure society of America Comprehensive Heart Failure Practice Guidelines

5 PROGNOSIS FOR SYSTOLIC DYSFUNCTION 1.0 Survival No LV Dysfunction (EF >50%) and no heart failure (HF) history Asymptomatic Mild LV Dysfunction (EF 40-50%).2.0 p < Asymptomatic Moderate to Severe LV Dysfunction (EF<40%) Symptomatic HF (EF 50%) Years Wang TJ et al. Circulation. 2003;108:

6 PROGNOSIS FOR DIASTOLIC DYSFUNCTION Survival in patients with normal left ventricular systolic function (LVEF) and reduced LVEF. LVEF < 50% 50% ANNUAL MORTALITY Mortality Control P value 18.9% 4.1% p < % 3.0% p < Vasan et al. JACC. 1999;33:

7 PROGNOSIS FOR DIASTOLIC DYSFUNCTION Survival in first year after first hospitalization for heart failure not significant between patients with normal (LVEF) > 50% and reduced LVEF < 40% (p = 0.18 adjusted). Bhatia et al. NEJM. 2006: 355:

8 FUNCTIONAL STATUS NYHA Functional Class 1 A ACC/AHA Heart Failure Stage 2 High risk for heart failure without structural heart disease or symptoms. I Asymptomatic B Structural heart disease but without symptoms of heart failure. II III Symptomatic with moderate exertion Symptomatic with minimal exertion C Structural heart disease with prior or current symptoms of heart failure. IV Symptomatic at rest D Refractory heart failure requiring specialized interventions Adapted from: Farrell MH et al. JAMA. 2002;287: New York Heart Association/Little Brown and Company, Hunt SA et al. J Am Coll Cardiol. 2001;38:

9 CLASSIFICATION OF HEART FAILURE A B C D STAGE High risk for heart failure Asymptomatic, structural heart disease Prior or current symptoms of heart failure Refractory end-stage heart failure PATIENT DESCRIPTION Hypertension Coronary artery disease Diabetes mellitus Family history of cardiomyopathy Previous myocardial infarction Left ventricular systolic dysfunction Asymptomatic valvular disease Known structural heart disease Shortness of breath and fatigue Reduced exercise tolerance Marked symptoms at rest despite maximal medical therapy. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

10 INITIAL ASSESSMENT OF HEART FAILURE Hot Spring in Yelowstone by Tobias Lee History and physical examination including discussion of alcohol, illicit drug, alternative therapy use, and prior chemotherapy. Assessment of functional status. Assessment of volume status, orthostatic blood pressure changes, height, weight, and body mass index (BMI). Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

11 INITIAL ASSESSMENT OF HEART FAILURE The Evolution of Man The Economist Routine chemistry, BUN, creatinine, Ca ++, Mg ++, CBC, urinalysis, lipids profile, liver function studies, and TSH. CXR and 12 lead electrocardiogram (ECG). Two dimensional echocardiography with Doppler. Coronary angiography if angina or ischemia present. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

12 ECHOCARDIOGRAM The single most useful diagnostic test in the evaluation of patients with heart failure is the comprehensive 2-dimensional echocardiogram coupled with Doppler flow studies to determine whether abnormalities of myocardium, heart valves, or pericardium are present. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure Yale Atlas of Echocardiography online at

13 ECHOCARDIOGRAM ASSESSMENT Normal left ventricular systolic function. Yale Atlas of Echocardiography online at

14 ECHOCARDIOGRAM ASSESSMENT Dilated Cardiomyopathy. UpToDate online at

15 ECHOCARDIOGRAM ASSESSMENT Diastolic Dysfunction. UpToDate online at

16 ACC/AHA CLASS C I RECOMMENDATIONSR D C B A HEART FAILURE STAGE Other advanced therapies. End of life care. Diuretic. Impantable defibrillator. Other targeted therapies. ACE Inhibitors Beta Blockers Treatment of risk factors. Avoidance of bad habits. COMMENTS Transplantation if eligible. Advanced therapies. End of life care discussions. Salt restriction, exercise training, aldosterone antagonist, ICD (LVEF 30%, > 1 yr expected survival, max med Rx), CRT (QRS > 120 msec, > 1 yr expected survival, max med Rx). Addition of ACE inhibitors and beta blockers for patients with and without prior myocardial infarction. Treatment of hypertension, dyslipidemia, and diabetes to current guideline recommendations. ACE inhibitors if other compelling reasons. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

17 GOALS OF DISCUSSION Quick Review of Heart Failure. Update on Drug Management. Update on Device Management. Focus on Diastolic Dysfunction. Tree on a Hill by Tobias Lee

18 INITIATION OF BETA BLOCKERS Geyser in Yellowstone by Tobias Lee Whenever possible, beta blocker therapy should be initiated in the hospital setting at a low dose prior to discharge in stable patients. Adams KF, J Lindenfeld et al Heart failure society of America Comprehensive Heart Failure Practice Guidelines

19 IMPACT-HF TRIALT 363 consecutive patients. Heart failure hospitalization. Randomized, open-label. Initiation of beta blockers: Prior to discharge or Postdischarge initiation Endpoint 60 day beta blocker use. 100% 75% 50% 25% 0% p < Prehospital Post discharge 91.2% 73.4% Gattis et al. JACC 2004: 43:

20 DENMARK EXPERIENCE 96,663 patient with first hospitalization for heart failure in Denmark After first 90 days of discharge if the patient was not on an ACE inhibitors, beta blockers, or spironolactone, only 5% of these patients started these medications. Gislason et al JACC Abstract

21 A-HEFT TRIALT 1050 black patients NYHA Class III-IV Standard therapy Placebo vs isosorbide dinitrate & hydralazine Endpoint Death Treatment 6.2% Control 10.2% NNT 24 Endpoint death, heart failure hospitalization, changes in quality of life. Hospital 16.4% 24.4% 12.5 Taylor et al NEJM 2004;

22 GOALS OF DISCUSSION Quick Review of Heart Failure. Update on Drug Management. Update on Device Management. Focus on Diastolic Dysfunction. Tree on a Hill by Tobias Lee

23 CAUSE OF DEATH IN HF PATIENTSP NYHA II CHF NYHA III CHF 12% Other 26% Other 64% 24% Sudden Death n = % 15% Sudden Death n = 103 MERIT-HF Study Group. Lancet. 1999;353:

24 SUDDEN CARDIAC DEATH Stroke 3 Lung Cancer 2 162, ,969 Sudden Cardiac Death claims more lives each year than these other diseases combined. 450,000 Sudden Cardiac Arrest 4 Breast Cancer 2 AIDS 1 41,809 42,156 1 U.S. Census Bureau, Statistical Abstract of the United States: American Cancer Society Cancer Statistics American Heart Association Heart Disease and Stroke Update Circulation. 2001;104: Adapted and updated from Prevention of Sudden Cardiac Death in Heart Failure Patients by William T. Abraham, MD

25 ICD CLASS I RECOMMENDATIONS ICD CLASS I RECOMMENDATIONS An implantable cardioverter-defibrillator is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of heart failure and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. Reiffel and Dizon 2002 Circulation 105: 1022 Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

26 ICD CLASS I RECOMMENDATIONS ICD CLASS I RECOMMENDATIONS An ICD is recommended for primary prevention to reduce total mortality from sudden cardiac death in patients 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 good functional status for more than 1 year. Zimetbaum and Josephson 2003 NEJM 348: Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

27 ICD CLASS I RECOMMENDATIONS ICD CLASS I RECOMMENDATIONS An ICD 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. Heart Rhythm Society of America Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

28 CARDIAC RESYNCHRONIZATION THERAPY Approximately one-third of patients with low ejection fraction and class III to IV symptoms of heart failure manifest a QRS duration greater than 120 milliseconds. Right Atrial Lead Left Ventricular Lead Right Ventricular Lead Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

29 COMPANION STUDY S CRT 1,520 patients NYHA class III and IV QRS 120 msec CRT vs CRT-D vs standard therapy DEATH & HOSPITALIZATION AT 12 MONTHS Group CRT CRT-D Treatment 56% 56% Control 68% 68% NNT 8 8 CRT = Cardiac Resynchronization Therapy CRT = CRT + Defibrillator NYHA = New York Heart Association Class Bristow et al. NEJM. 2004; 350:

30 CARE-HF 813 patients NYHA class III and IV QRS 120 msec CRT vs standard therapy DEATH & HOSPITALIZATION AT MEAN 29 MONTHS Group Treatment Control NNT Endpoint 39% 55% 6 Death 20% 30% 10 NYHA = New York Heart Association Class Cleland et al. NEJM. 2005; 352:

31 CRT CLASS I RECOMMENDATIONS CRT CLASS I RECOMMENDATIONS Moon in Yellowston by Tobias Lee Patients with LVEF 35%, sinus rhythm, and NYHA 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 milliseconds, should receive cardiac resynchronization therapy unless contraindicated. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

32 SUMMARY OF ICD RECOMMENDATIONS Recommended for secondary prevention in patients with systolic dysfunction with a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. More than 40 days post-mi, LVEF 30%, NYHA II-III. Nonischemic cardiomyopathy, LVEF 30%, NYHA II-III. Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

33 NUMBER NEEDED TO TREAT NNT x years = 100 / (% Mortality in Control Group % Mortality in Treatment Group) ICD/CRT Therapy Drug Therapy amiodarone metoprolol simvastatin captopril 0 MADIT MADIT II COMPANION ScD-HeFT CARE-HF SAVE Merit-HF 4S Amiodarone Meta-analysis (2.4 Yr) (3 Yr) (1 Yr) (5 Yr) (2.4 Yr) (3.5 Yr) (1 Yr) (6 Yr) (2 Yr) Adapted and updated from Prevention of Sudden Cardiac Death in Heart Failure Patients by William T. Abraham, MD

34 GOALS OF DISCUSSION Quick Review of Heart Failure. Update on Drug Management. Update on Device Management. Focus on Diastolic Dysfunction. Tree on a Hill by Tobias Lee

35 DIASTOLIC HEART FAILURE ALL THE CLASS I RECOMMENDATIONS Control blood pressure according to guidelines. Control ventricular rate in atrial fibrillation. Use diuretics as needed to control symptoms. Waterfall in Yellowstone by Tobias Lee Hunt SA, et al. ACC/AHA 2005 Guideline Update for Chronic Heart Failure

36 DIASTOLIC HEART FAILURE Adams KF, J Lindenfeld et al Heart failure society of America Comprehensive Heart Failure Practice Guidelines

37 CHARM-PRESERVED RESERVED TRIAL Candesartan in Heart Failure: Assessment of Reduction of Mortality and Morbidity. 3,023 patients with LVEF > 40% (Mean 54%). Candesartan (target dose 32 mg daily) versus placebo. Follow-up 2 years. No significant difference in cardiovascular death or heart failure hospitalization. Yusuf et al Lancet 362:

38 CONCLUSIONS Quick Review of Heart Failure. Update on Drug Management. Update on Device Management. Focus on Diastolic Dysfunction. Thank you! Tree on a Hill by Tobias Lee

39 WEB REFERENCES American College of Cardiology Cardiac Study Center Cardiosource Heart Failure Society of America Sunset at Yellowstone by Tobias Lee