What is the effect of digoxin on the heart?

Effect of Digoxin on the Heart

Digoxin exerts three primary cardiac effects: it increases myocardial contractility (positive inotropic action), slows heart rate and AV node conduction (vagomimetic effect), and reduces sympathetic nervous system activation (neurohormonal deactivation). 1

Mechanism of Action

Digoxin works by inhibiting sodium-potassium ATPase, which leads to increased intracellular calcium concentrations in cardiac muscle cells 1. This produces both direct cardiac effects and indirect effects mediated through the autonomic nervous system:

Direct Cardiac Effects

• Increased force and velocity of myocardial systolic contraction (positive inotropic action) 1
• Enhanced left ventricular ejection fraction in patients with chronic heart failure 2
• Improved exercise tolerance in patients with mild to moderate heart failure 2, 3

Autonomic and Neurohormonal Effects

• Vagomimetic action on the sinoatrial and AV nodes, resulting in slowed heart rate and decreased AV node conduction velocity 1
• Baroreceptor sensitization, which increases afferent inhibitory activity and reduces sympathetic nervous system and renin-angiotensin system activity 1
• Reduced sympathetic outflow as a major mechanism of benefit in heart failure 2

Clinical Cardiac Effects by Condition

In Heart Failure with Reduced Ejection Fraction (Sinus Rhythm)

• Improves symptoms, quality of life, and exercise capacity regardless of underlying etiology 2, 3
• Reduces hospitalizations for worsening heart failure by 28% (NNT=13 over 3 years) 2, 4
• Does not reduce mortality but prevents clinical deterioration 2
• Most beneficial in patients with severe heart failure, cardiomegaly, and third heart sound 5
• Not efficacious in asymptomatic patients with ventricular systolic dysfunction 2

In Atrial Fibrillation

• Controls ventricular rate primarily through vagotonic effects on the AV node 2, 4
• Most effective at rest and in sedentary patients with low sympathetic tone 6, 5
• Less effective during exercise compared to beta-blockers or calcium channel blockers 6
• Should be used in combination with beta-blockers for optimal rate control, particularly during physical activity 4, 3

Important Cardiac Safety Considerations

Contraindications

Do not use digoxin in patients with: 4, 1

• Second- or third-degree heart block without a permanent pacemaker
• Pre-excitation syndromes (Wolff-Parkinson-White)
• Suspected sick sinus syndrome (use with extreme caution)

Arrhythmogenic Potential

• Can cause atrial and ventricular arrhythmias, particularly with hypokalemia, hypomagnesemia, or hypercalcemia 2, 1
• High doses increase sympathetic outflow from the CNS, which may contribute to digitalis toxicity 1
• Risk increases with serum levels >2.0 ng/mL, but toxicity can occur at lower levels if electrolyte abnormalities coexist 1, 3

Electrolyte Interactions

Mandatory serial monitoring of serum potassium, magnesium, and renal function is required because: 2, 4, 1

• Hypokalemia and hypomagnesemia sensitize the myocardium to digoxin toxicity
• Hypercalcemia predisposes to digitalis toxicity and serious arrhythmias
• Hypocalcemia can nullify digoxin's cardiac effects

Drug Interactions Affecting Cardiac Effects

Amiodarone, diltiazem, verapamil, quinidine, and certain antibiotics increase digoxin levels—reduce digoxin dose by 50% when adding these agents 4, 1, 3. The additive effects of beta-blockers or calcium channel blockers with digoxin on AV node conduction can result in advanced or complete heart block 1.

Optimal Dosing for Cardiac Effects

Start with 0.125 mg daily (or every other day) in patients >70 years old, with renal impairment, or low lean body mass 2, 4. Use 0.25 mg daily only in younger adults with normal renal function 4. Target therapeutic serum concentration of 0.5-0.9 ng/mL (or 0.6-1.2 ng/mL per some guidelines) provides optimal cardiac benefits with minimal toxicity risk 2, 4. Loading doses are unnecessary in stable outpatients with chronic heart failure 4, 3.

Common Pitfall to Avoid

Do not use high doses of digoxin (>0.25 mg daily) for rate control in atrial fibrillation—instead, add a beta-blocker or amiodarone for additional rate control 3. The cardiac benefits of digoxin occur at relatively low doses, and higher doses increase toxicity risk without improving efficacy 3, 7.