Treatment of Heart Failure Claire Hunter, MD

Treatment of Heart Failure Goals Improve quality of life Prolong life Ejection fraction most important prognostic factor Those with ejection fraction less than 20% have 50% 1-2 year survival

Treatment strategy Etiology of heart failure Precipitating agents of circumstances Evaluation of decompensation Nonpharmacologic and pharmacologic treatments

Etiology of Insult to myocardium Infarction/Ischemia--loss of myocyte function Pressure overload hypertensive heart disease aortic stenosis pulmonic stenosis hypertrophic cardiomyopathy Volume overload aortic regurgitation mitral regurgitation

Etiology continued Idiopathic dilated cardiomyopathy (may be viral) Infiltrative in myocardium or interstitium sarcoid iron(hemochromatosis) amyloid radiation fibrosis chemotherapeutic agents (anthracyclines)

Precipitating agents or circumstances Ischemia Dietary or medication noncompliance (sodium intake) Work overload--emotional stress or isometric activity Arrhythmias--atrial or ventricular

Evaluation of decompensation Dietary review “Pill count” Review social circumstances and enlist aid of social worker if needed Echocardiography--reassess left ventricular function, valvular abnormalities Arrhythmias Ischemia evaluation (imaging stress or angiography

Nonpharmacologic treatments Dietary reinforcements mg Na daily Rest (not necessarily bed rest) Decrease stress Assess any added medications that are deleterious nonsteroidal antiinflammatory agents

Pharmacologic treatments Positive inotropic agents digitalis catecholamines phosphodiesterase inhibitors

Digitalis Has not been proven to prolong survival Decreases hospitalizations Slight increase in arrhythmias Improves symptoms of congestion

Catecholamines Dobutamine (synthetic) Dopamine Increase heart rate and myocardial oxygen demand Tolerance to effects develops after 72 hours Have not been proven long term to improve survival

Phosphodiesterase Inhibitors Milrnone, amrinone In some trials increase mortality ( oral form and with chronic treatment) Short term intravenous treatment decreases pulmonary hypertension and left ventricular filling pressures; but may increase ventricular arrhythmias

Mechanism of heart failure Loss of myocardial function triggers SYMPATHETIC NERVOUS SYSTEM to compensate Cardiac output - heart rate x stroke volume Increases constricting and volume expanding hormones

Mechanism continued Failing heart down regulates B 1 receptors Increased filling pressure in ventricle triggers plasma renin angiotensin system (vasoconstriction and increased afterload)

Afterload reduction ACE inhibitors (angiotensin converting enzyme) ARB (angiotensin receptor blockers) Direct arterial dilators

Angiotensin converting enzyme inhibitors Proven to reduce development of overt heart failure in with asymptomatic left ventricular dysfunction Proven to prolong survival Reduce microalbuminuria in diabetics

Angiotensin Receptor Blockers Mortality results have been mixed in studies Beneficial symptomatically Whether equal to ACE inhibitors remains to be seen

Direct arterial dilators Hydralazine best oral example Nitroprusside best parenteral example Hydralazine used in combination with nitrates proven to prolong survival Not as good as ACE inhibitors at reducing mortality

Beta blockers Sympathetic activation Leads to increased circulating catecholamines By way of the B 1 receptor they Activate the Gs protein which Activates adenylate cyclase which Activates cAMP(increases) Activate protein kinase Leads to increased intracellular calcium Leads to improved contractility

Beta receptor down regulation Occurs with sympathetic overstimulation Receptor uncoupling Leads to increased Gi (tonic inhibition) Calcium overload (toxic to myocardium)

Beta blockers Negative inotropic agents initially Restore B1 density and thus lead to Ultimate biologic improvement of ejection fraction Negate arrhythmogenic effects of catecholamines

Beta blockers Improve survival Selective Sustained release metoprolol Bisoprolol Nonselective Carvedilol (added value of antioxidant and alpha effects)

Diuretics Treat volume overload Relieve symptoms of congestion Do not affect survival Do not alter remodelling

Diuretics continued Thiazides Loop diuretics Metolozone

Spironolactone Improves survival for Class III or IV heart failure Most likely due to effects on interstitium, not diuretic effects Potassium retention Beware of use in those whose creatinine is more than 2.5

Actions of BNP Hemodynamic balanced vasodilation coronary arteries Neurohormonal decreases aldosterone decreases endothelin Renal increases diuresis increases natriuresis

BNP as a Therapeutic

Disease Management Telemonitoring Weekly educational mailings Medical claims declined by $1100 per patient in treatment group Claims increased $9600 in non-treatment group

Goals of Treatment Improve cardiac function and survival with ACE inhibitors Beta blockers Diuretics if needed for symptoms Spironolactone for Class III or IV

Accomplish these goals Decreasing sympathetic drive and its toxic effects on the myocardium Decreasing the constricting hormones that increase afterload and increase the work for the heart Positively impact remodelling so the heart can be more efficient