Pharmacotherapy of Heart Failure

DEFINITION
A pathophysiological condition where the heart
is incapable of maintaining a cardiac output
adequate to accommodate metabolic requirements and the venous return."

E. Braunwald

The principal goals of Treatment are; 1. Improve / prevent symptoms from worsening 2. To improve / maintain quality of life & to delay death.

3. Avoid side effects of treatment & decrease occurrence of major morbid events

Types of Heart Failure

Acute & Chronic heart failure Left & Right heart failure Systolic & Diastolic heart failure Low & High output failure

Symptoms & Signs of HF:

Fatigue (low cardiac out-put) Shortness of breath JVP Rales Edema Radiologic congestion Cardiomegaly

DIET Approach to the Patient With Heart Failure

Diagnose
Etiology Severity (LV dysfunction)

Educate
Diet Exercise Lifestyle CV Risk

Initiate
Diuretic/ACE inhibitor -blocker Spirololactone Digoxin

Titrate
Optimize ACE inhibitor Optimize diuretics

Drugs used for Tt of Heart Failure

Positive inotropic drugs Cardiac Gylcosides Digoxin, Digitoxin -Phosphodiesterase inhibitors: cAMP dependent --Milrinone, Inamrinone. ACE Inhibitors Enalapril, Lisinopril Angiotensin II Receptor Blockers (ARBs)- Losartan, Diuretics Frusemide, Spironolactone Vasodilators--Hydralazine, Sodium Nitropruside

Cardiac glycosides
Foxglove - Digitalis purpurea Extract called digitalis Long history as a folk remedy for congestive heart failure William Withering investigated this remedy from 17751785 - first scientific study of a medicinal plant

Currently available cardiac glycosides

Digoxin, digitoxin & ouabain

Digoxin is the most preferred

Digitalis purpurea

Mechanism of Action
Na-K ATPase

K+

Na-Ca Exchange

Na+

Ca++

Na+

Myofilaments

Ca++

CONTRACTILITY

DIGOXIN
Na-K ATPase

Na-Ca Exchange
Na+ Ca2+

K+

Na+ Na+

Ca2+
SR

Ca2+

Ca2+

Mechanism of Action

Inhibit Na-K ATPase, intracellular Na Ca through Na-Ca exchange which causes contraction of the myocardium.

Pharmacologic Actions
1. Increases Cardiac Output 2. Indirectly decreases sympathetic nervous system activity
Arteriolar dilation Venous dilation

3. Causes Vagal stimulation

Cardiac glycosides
As a positive inotropic drug, digitalis improves myocardial contractility
Useful in systolic heart failure

Still the drug of choice for patients with CHF and rapid atrial fibrillation

Electrophysiological Effects
Decrease conduction velocity Decreases action potential duration: decreases refractory period in ventricles
Enhances automaticity due to
Steeper phase 4 Afterdepolarizations

Parasympathomimetic Effects
Decreases conduction velocity in the AV node Increases effective refractory period in the AV node Causes Heart block (toxic concentrations)

Digitalis
Uses 1. Chronic Heart Failure 2. Atrial fibrillation
Overall Benefit of Digitalis to Myocardial Function cardiac output cardiac efficiency heart rate cardiac size

Digitalis Adverse Effects

Cardiac AV block Bradycardia Ventricular extrasystole Arrhythmias Extra-Cardiac GI Nausea, Vomiting, Anorexia CNS Disorientation, Hallucinations Misc - Gynecomastia

Serum Electrolytes & Digoxin

K+
Digitalis competes for K binding at Na/K ATPase Hypokalemia: increase toxicity Hyperkalemia: decrease toxicity

Mg2+
Hypomagnesemia: increases toxicity

Ca2+
Hypercalcemia: increases toxicity

Treatment of Digitalis Toxicity

Stop/Reduce digoxin dose: Atropine- Corrects heart block KClAntiarrythmics- ventricular arrhythmiasLignocaine or Phenytoin

Antidigoxin Immunotherapy -Fab antibodies-

Heart Failure Therapeutic Goal

Mild-Moderate Heart Failure Primary goal = Reduce mortality ACE inhibitors Diuretics Prevent progression to symptoms Prevent progressive LV dysfunction

Heart Failure Therapeutic Goal

Moderate-Severe Heart Failure Primary goal = Reduce symptoms Improve quality of life (QOL) Reduce hospitalizations Prevent sudden death