1. Pharmacologic Treatment of Chronic Systolic Heart Failure John N. Hamaty D.O. FACC, FACOI

2. Heart Failure Final common pathway in most heart diseases Final common pathway in most heart diseases 550,000 new cases each year 550,000 new cases each year 20.1/100,000 mortality rate 20.1/100,000 mortality rate No change in mortality No change in mortality

3. Diastolic Heart Failure Impaired ability to accept blood and relax during diastole Impaired ability to accept blood and relax during diastole Both types increase with age, African Americans Both types increase with age, African Americans 40-70% incidence more often female, obese, older HTN and less likely to have CAD 40-70% incidence more often female, obese, older HTN and less likely to have CAD Less symptomatic and lower morbidity and mortality Less symptomatic and lower morbidity and mortality

6. B-Adrenergic Receptor Blockers Improve survival Improve survival Improve ejection fraction Improve ejection fraction Remodeling Remodeling Quality of life Quality of life Reduce SCD Reduce SCD Inhibiting adverse effects of the sympathetic nervous system Inhibiting adverse effects of the sympathetic nervous system Diminish RAAS activation Diminish RAAS activation

7. Angiotensin-Converting Inhibitors Decrease conversion of angiotensin I-II Decrease conversion of angiotensin I-II Improve survival Improve survival Decrease rate of hospitalization Decrease rate of hospitalization Improve symptoms Improve symptoms Inhibit neurohormonal activation Inhibit neurohormonal activation Reverse remodeling Reverse remodeling Decrease incidence of SCD? Decrease incidence of SCD?

8. Angiotensin Receptor Blockers Efficacy similar to ACE inhibitors Efficacy similar to ACE inhibitors Alternative to ACEI in patients not tolerant of ACEI Alternative to ACEI in patients not tolerant of ACEI VAL-HeFT- ACEI +B-BL+ARB increase morality VAL-HeFT- ACEI +B-BL+ARB increase morality CHARM- improve mortality CHARM- improve mortality

9. Competitive Aldosterone Antagonists Aldosterone stimulates renal sodium retention and myocardial hypertrophy Aldosterone stimulates renal sodium retention and myocardial hypertrophy Spironolactone decreases mortality and morbidity in NYH class III and IV Spironolactone decreases mortality and morbidity in NYH class III and IV

10. Selective Aldosterone Blockers Eplerenone (EPHESUS Trial)-post acute myocardial infarction trial Eplerenone (EPHESUS Trial)-post acute myocardial infarction trial When added to optimal medical therapy excluding spirnolactone When added to optimal medical therapy excluding spirnolactone Reduced morbidity and mortality in patients with acute MI with left ventricular dysfunction and heart failure Reduced morbidity and mortality in patients with acute MI with left ventricular dysfunction and heart failure

13. Future: New Insights Tissue doppler-decreased flow velocities predict LVH before it occurs Tissue doppler-decreased flow velocities predict LVH before it occurs Ultrasonic tissue character-tissue edema, fibrosis and calcification. Can predict tissue damage before it occurs in HTN Ultrasonic tissue character-tissue edema, fibrosis and calcification. Can predict tissue damage before it occurs in HTN Myocyte enhancer factor 2-developmental gene for CAD/nonischemic HF Myocyte enhancer factor 2-developmental gene for CAD/nonischemic HF

14. Pharmacogenetics Alpha-adducin gene-found it 2/3 HTN patients. Diuretics will not reduce risk Alpha-adducin gene-found it 2/3 HTN patients. Diuretics will not reduce risk Adrenergic receptors- 2 variants in African Americans. 10 fold risk of developing HTN and candidates for early tx with b-blockers Adrenergic receptors- 2 variants in African Americans. 10 fold risk of developing HTN and candidates for early tx with b-blockers

15. Conclusions Antagonizing this neurohormonal cascade has been the focus of recent clinical trials. Further directions in HF therapy are likely to focus on limiting or preventing activation of the neurohormonal cascade through earlier recognition and treatment of patients at risk for HF. Antagonizing this neurohormonal cascade has been the focus of recent clinical trials. Further directions in HF therapy are likely to focus on limiting or preventing activation of the neurohormonal cascade through earlier recognition and treatment of patients at risk for HF.