Digoxin Toxicity on ECG

What it looks like on ECG

The picture consists of two components: background "digitalis effect" on the ST-T segment and true toxic arrhythmias.

Digitalis effect — scoop-shaped (ladle-like) ST depression with downward sagging, transitioning into a flattened or mildly inverted T wave, best seen in leads with tall R waves (II, V5-V6). QT/QTc is frequently shortened due to action potential shortening, but this sign is variable (depends on HR, difficult to determine the end of the T wave amidst ST depression) and is not used independently to diagnose toxicity. This pattern often occurs at therapeutic concentrations of the drug, but by itself does not diagnose toxicity: it may persist at toxic concentrations as well. The diagnosis of toxicity is established based on symptoms, the appearance of new arrhythmias or blocks, electrolyte levels, renal function, and a correctly drawn blood digoxin concentration, rather than on an isolated ST-T shape.

Signs of true toxicity — a new rhythm or conduction disturbance in a patient on digoxin raises suspicion for toxicity, but does not confirm it by itself (another cause is possible), and its absence does not rule out toxicity:

Any of these findings are evaluated alongside clinical status, electrolytes, renal function, and digoxin concentration. QRS duration in pure glycoside toxicity is usually normal unless there is a concomitant bundle branch block or marked hyperkalemia (severe toxicity may feature concomitant hyperkalemia due to Na+/K+-ATPase blockade).

Mechanism

Digoxin inhibits cardiomyocyte Na+/K+-ATPase. In therapeutic doses, this increases intracellular Ca2+ via the sodium-calcium exchanger and enhances contractility (positive inotropic effect), as well as increasing vagal tone, slowing AV conduction. In overdose, excessive inhibition of Na+/K+-ATPase leads to cellular calcium overload, causing delayed afterdepolarizations (triggered activity) and ventricular ectopy, up to bidirectional VT. Simultaneously, enhanced vagal tone and direct toxic effects on the AV and sinus nodes depress automaticity and conduction, producing bradyarrhythmias and blocks. The combination of increased atrial ectopic activity with impaired AV conduction explains the classic finding — atrial tachycardia with block.

Causes

• Digoxin overdose (acute or on the background of chronic administration)
• Decreased renal excretion of digoxin in CKD or acute kidney injury in a patient taking the drug
• Hypokalemia — enhances digoxin binding to Na+/K+-ATPase and increases toxicity even at normal drug concentrations
• Hypomagnesemia, hypercalcemia — increase myocardial sensitivity to glycosides
• Hypothyroidism, older age, low muscle mass — decrease clearance and increase sensitivity
• Drug interactions increasing digoxin concentration (amiodarone, verapamil, certain macrolides, and other drugs competing for P-glycoprotein)

Differential diagnosis

• Digitalis effect without toxicity — isolated scoop-shaped ST depression without arrhythmias; this is the expected effect of a therapeutic dose and requires no treatment.
• Ischemic ST depression — more frequently horizontal or downsloping. ST-T morphology, presence or absence of QT shortening, and clinical presentation serve as guides but do not reliably differentiate ischemia from the digitalis effect: ischemia may be accompanied by QT changes, both conditions can coexist, and ischemia can be silent. When ACS is suspected, ST depression should not be dismissed as digoxin effect — evaluate ECG dynamics, troponin, and the clinical context.
• Hyperkalemia — may accompany severe digoxin toxicity (Na+/K+-ATPase inhibition), producing similar bradyarrhythmia and AV block; differentiated by serum potassium and digoxin levels.
• Atrial fibrillation with slow ventricular response of other etiology — during toxicity, rhythm regularization in AF is suspicious for the development of junctional rhythm or AV block.
• Bidirectional VT of other etiology (catecholaminergic polymorphic VT) — differentiated by the clinical setting (exercise/stress in young individuals vs. digoxin intake) and medical history.

Clinical significance and management

Digoxin toxicity is dangerous due to life-threatening ventricular arrhythmias and pronounced bradyarrhythmias, including complete AV block and asystole. A new rhythm or conduction disturbance in a patient taking digoxin should raise suspicion for toxicity and requires assessment of clinical status, electrolytes, renal function, and digoxin concentration; by itself, it does not confirm the diagnosis, and the absence of changes does not exclude it.

For the physician at the algorithmic level: evaluate serial ECGs, determine blood concentrations of digoxin, potassium, magnesium, and calcium, and assess renal function. Digoxin concentration is drawn taking into account the time of the last dose, usually no earlier than 6–8 hours post-dose (prior to tissue distribution, blood levels are artificially elevated); the result is interpreted alongside clinical status, ECG, potassium, and renal function — an early level and a "therapeutic" value do not rule out toxicity, especially chronic toxicity. Discontinue the drug.

In unstable bradycardia or AV block — support ABC, atropine if no contraindications exist (may be effective, particularly with a vagal mechanism). In severe and life-threatening toxicity (ventricular tachyarrhythmias, pronounced bradyarrhythmias and blocks with hemodynamic compromise, hyperkalemia) — administer specific antidote (digoxin-specific antibody Fab fragments) urgently. Temporary pacing may be used for persistent symptomatic bradycardia or block refractory to medical therapy, but is performed with caution and monitoring — against the background of glycoside toxicity, it can provoke ventricular arrhythmias.

Potassium is measured before treatment and serially: hypokalemia is corrected cautiously as it exacerbates digoxin toxicity, while hyperkalemia is treated according to standard emergency protocols without delaying correction until antidote administration; in life-threatening digoxin toxicity with hyperkalemia, the primary specific treatment is Fab fragments. Empirical administration of potassium-lowering drugs without checking serum potassium should be avoided. Electrical cardioversion for severe ventricular arrhythmias is used with caution — the risk of refractory VF following the shock is increased in glycoside toxicity.

Common interpretation errors

• Mistaking an isolated digitalis effect (ST depression) for a sign of toxicity and discontinuing a necessary medication without clinical data
• Dismissing ST depression in a patient on digoxin as a "digitalis effect" without ruling out concomitant ischemia when ACS is suspected
• Failing to notice rhythm regularization in AF as a sign of developing junctional tachycardia or AV block
• Do not miss atrial tachycardia with block behind a rapid ventricular rate, mistaking it for simple second-degree AV block
• Forget to check potassium levels — hypokalemia drastically increases sensitivity to digoxin even at a "normal" concentration

Frequently asked questions

Related terms

More in "Pharmacology and Toxicology"

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Sources

• Goldberger's Clinical Electrocardiography, 9th ed.
• Surawicz B., Knilans T. Chou's Electrocardiography in Clinical Practice, 6th ed.
• Orlov V.N. Guide to Electrocardiography
• Hampton J. The ECG in Practice, 6th ed.

Educational material for medical students and physicians. Does not replace clinical guidelines and physical examination; the ECG must always be interpreted in conjunction with the clinical picture.