Pharmacologic Pharmacologic Treatment of Chronic Treatment of Chronic Systolic Heart FailureSystolic Heart Failure

John N. Hamaty D.O. FACC, John N. Hamaty D.O. FACC, FACOIFACOI

Heart FailureHeart Failure

Final common pathway in most heart Final common pathway in most heart diseasesdiseases

550,000 new cases each year550,000 new cases each year 20.1/100,000 mortality rate20.1/100,000 mortality rate No change in mortality No change in mortality

Diastolic Heart FailureDiastolic Heart Failure

Impaired ability to accept blood and Impaired ability to accept blood and relax during diastolerelax during diastole

Both types increase with age, African Both types increase with age, African AmericansAmericans

40-70% incidence more often female, 40-70% incidence more often female, obese, older HTN and less likely to obese, older HTN and less likely to have CADhave CAD

Less symptomatic and lower Less symptomatic and lower morbidity and mortalitymorbidity and mortality

B-Adrenergic Receptor B-Adrenergic Receptor BlockersBlockers

Improve survivalImprove survival Improve ejection fractionImprove ejection fraction RemodelingRemodeling Quality of lifeQuality of life Reduce SCDReduce SCD Inhibiting adverse effects of the Inhibiting adverse effects of the

sympathetic nervous systemsympathetic nervous system Diminish RAAS activationDiminish RAAS activation

Angiotensin-Converting Angiotensin-Converting InhibitorsInhibitors

Decrease conversion of angiotensin I-Decrease conversion of angiotensin I-IIII

Improve survivalImprove survival Decrease rate of hospitalizationDecrease rate of hospitalization Improve symptomsImprove symptoms Inhibit neurohormonal activationInhibit neurohormonal activation Reverse remodelingReverse remodeling Decrease incidence of SCD?Decrease incidence of SCD?

Angiotensin Receptor Angiotensin Receptor BlockersBlockers

Efficacy similar to ACE inhibitorsEfficacy similar to ACE inhibitors Alternative to ACEI in patients not Alternative to ACEI in patients not

tolerant of ACEItolerant of ACEI VAL-HeFT- ACEI +B-BL+ARB increase VAL-HeFT- ACEI +B-BL+ARB increase

moralitymorality CHARM- improve mortalityCHARM- improve mortality

Competitive Aldosterone Competitive Aldosterone AntagonistsAntagonists

Aldosterone stimulates renal sodium Aldosterone stimulates renal sodium retention and myocardial retention and myocardial hypertrophyhypertrophy

Spironolactone decreases mortality Spironolactone decreases mortality and morbidity in NYH class III and IVand morbidity in NYH class III and IV

Selective Aldosterone Selective Aldosterone BlockersBlockers

Eplerenone (EPHESUS Trial)-post Eplerenone (EPHESUS Trial)-post acute myocardial infarction trialacute myocardial infarction trial

When added to optimal medical When added to optimal medical therapy excluding spirnolactonetherapy excluding spirnolactone

Reduced morbidity and mortality in Reduced morbidity and mortality in patients with acute MI with left patients with acute MI with left ventricular dysfunction and heart ventricular dysfunction and heart failurefailure

Future: New InsightsFuture: New Insights

Tissue doppler-decreased flow Tissue doppler-decreased flow velocities predict LVH before it occursvelocities predict LVH before it occurs

Ultrasonic tissue character-tissue Ultrasonic tissue character-tissue edema, fibrosis and calcification. Can edema, fibrosis and calcification. Can predict tissue damage before it occurs predict tissue damage before it occurs in HTNin HTN

Myocyte enhancer factor 2-Myocyte enhancer factor 2-developmental gene for developmental gene for CAD/nonischemic HFCAD/nonischemic HF

PharmacogeneticsPharmacogenetics

Alpha-adducin gene-found it 2/3 HTN Alpha-adducin gene-found it 2/3 HTN patients. Diuretics will not reduce patients. Diuretics will not reduce riskrisk

Adrenergic receptors- 2 variants in Adrenergic receptors- 2 variants in African Americans. 10 fold risk of African Americans. 10 fold risk of developing HTN and candidates for developing HTN and candidates for early tx with b-blockersearly tx with b-blockers

ConclusionsConclusions

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