CH 51. Heart Failure and Meds

Types of Heart Failure

• Heart failure: progressive often fatal disorder, characterized by LV dysfunction, reduced cardiac output, insufficient tissue perfusion, and signs of fluid retention

• Left ventricular systolic dysfunction: LV weakens, reduced ejection fraction, Heart can’t pump enough blood to meet the body’s needs. 

• Diastolic Heart Failure: normal LV ejection fraction; and abnormal diastolic filling pattern

Managment of Heart Failure

• Stage A: no symptoms of HF, no structural or functional cardiac abnormalities, goal is to reduce risk (lifestyle changes, manage hypertension, coronary artery disease, diabetes etc)

• Stage B: no symptoms of HF, goal is to prevent development of symptomatic HF

• Treatment is same as stage A with the addition of ACE inhibitors  and ARB’s 

• Stage C: symptoms of HF, structural heart disease

• Four major goals 

• Relieve pulmonary and peripheral congestive symptoms 

• Improve functional capacity and quality of life

• Slow cardiac remodeling and LV dysfunction

• Prolong life

• Avoid: antidysrhythmic agents, calcium channel blockers, NSAIDS and aspirin 

• Devices may be implanted ( cardiodioverter-defibrillators)

 Stage D: Marked symptoms of HF, Advanced structural heart disease, repeated hospitalizations 

• Best solution is a heart transplant

• Implant LV mechanical assist device until heart is available

• Control fluid retention (diuretics, dopamine)

• Beta blockers pose high risk of worsening HF 

Pathophysiology of Heart Failure 

• characterized by LV dysfunction, reduced cardiac output, 

• insufficient tissue perfusion,

• Volume overload 

• Chronic hypertension

• Myocardial infarction

• Valvular heart disease

• coronary artery disease

• congenital heart disease 

• Dysrhythmias

• Aging of the myocardium 

• Cardiac remodeling 

• Physiologic adaptations to reduced cardiac output: 

• Cardiac dilation 

• Increased sympathetic tone 

• Water retention and increased blood volume 

• Natriuretic peptides 

Drugs for Heart Failure 

• Diuretics: Loop, Thiazide, Potassium sparing 

• RAAS inhibitors (ACE inhibitors, angiotensin 2 receptor blockers, aldosterone antagonists, direct renin inhibitors)

• Beta blockers

• Digoxin 

• Dopamine 

• Hydralazine 

Adverse effects of vasodilators

• postural hypotension

• Reflex tachycardia

• Expansion of blood volume 

• ACE (angiotensin converting enzyme) inhibitors 

Overall effects and MOA

• Arteriolar dilation

• Venous dilation

• Suppression of aldosterone release

• Have a favorable impact on cardiac remodeling 

Adverse effects of ACE inhibitors

• Hypotension

• Hyperkalemia

• Cough

• Angioedema

• Renal failure (if problems already present)

• Fetal injury

• Angiotensin 2 receptor blockers 

Overall effects

• Improve ejection fraction

• Reduce HF symptoms

• Increase exercise tolerance

• Decrease hospitalization 

• Reduce mortality 

• Aldosterone antagonists [spironolactone, inspra]

Therapeutic Uses 

• Add to HF therapy in patients with moderate or severe symptoms

• Direct renin inhibitors

Overall effects 

• Benefits in HF equal to ACE inhibitors and ARB’s

• Beta Blockers

Overall effects and MOA

• Protect against dysrhythmias/excessive sympathetic stimulation

Adverse effects of Beta blockers 

• Hypotension

• Fluid retention or worsening of HF

• Fatigue

• Bradycardia or Heart block 

• Beta Blockers

Overall effects and MOA

• Positive inotropic actions 

• Increase myocardial contractile force 

• Alter electrical activity of the heart 

• Favorably affect neurohormonal systems 

• Second line agents in HF treatment 

Inotropic Agents

• Dopamine [intropin] (Class: sympathomimetic)

Overall effects and MOA

• Catecholamine 

• Activates beta adrenergic receptors in heart, kidney and blood vessels 

• Increases Heart rate

• Dilates renal vessels 

• Activates alpha 2 receptors  

• Increase myocardial contractile force 

• Alter electrical activity of the heart 

• Favorably affect neurohormonal systems 

• Second line agents in HF treatment 

• Dobutamine 

Overall effects and MOA

• Synthetic Catecholamine 

• Selective activation of beta 2 adrenergic receptors

Phosphodiesterase Inhibitors 

• Milrinone [primacor]

• Milrinone [Primacor]

Overall effects and MOA

• Inodilator: increases myocardial contractility and promotes vasodilation

• Reserved for patients with severe reduction in cardiac output resulting in decreased organ perfusion

• Treats arrhythmias and myocardial ischemia 

 IV Vasodilators for acute care 

• Nitroglycerin

Principal Adverse effects 

• Hypotension 

• Tachycardia 

• Sodium nitroprusside [nitropress]

Principal Adverse effects 

• Profound hypotension

Cardiac (Digitalis) glycosides 

Examples: Digoxin [lanoxin, lanoxicaps, digitek]

Overall effects and MOA

• Profound effects on mechanical and electrical properties of the heart

• Increases myocardial contractility 

• Increases cardiac output

Adverse effects 

• Severe dysrhythmias 

• Digoxin [Lanoxin]

Overall effects and MOA

• Positive inotropic action on the heart

• Increases force of ventricular contraction

• Increases myocardial contractility

Note: Potassium levels must be kept in normal physiologic range 

Hemodynamic benefits of Digoxin

• Increased cardiac output

• Decreased sympathetic tone

• Increased urine production

• Decreased renin release 

Neurohormonal benefits of Digoxin

• Modulates activity of neurohormonal system 

• Suppresses renin release 

• Decreases sympathetic outflow from the CNS

• Increases sensitivity of the cardiac baroreceptors

Electrical effects of Digoxin

• Increases firing rate of vagal fibers 

• Increases responsiveness of SA node to acetylcholine 

Adverse effects of Digoxin

• Cardiac dysrhythmias

• Hypokalemia and elevated digoxin level (predisposing factors)  

Note: therapeutic range of digoxin is 0.5-0.8

• Anorexia, vomiting, nausea, fatigue 

Drug interactions of digoxin

• Diuretics 

• ACE inhibitors and ARB’s 

• Sympathomimetics (dopamine)

• Quinidine

• Verapamil