Mechanism of action of cardiac glycosides
Cardiac glycosides (digoxin, digitoxin, etc.) exert their positive inotropic effect by inhibiting two key membrane transport systems of the cardiomyocyte.
- The primary blockade targets Na⁺/K⁺-ATPase, which normally pumps 3 sodium ions out of the cell in exchange for 2 potassium ions entering.
- As a result, intracellular sodium concentration increases, which secondarily inhibits the Na⁺/Ca²⁺ exchanger, which normally expels 1 calcium ion from the cell in exchange for 3 sodium ions entering.
- The accumulation of intracellular calcium facilitates the interaction of actin and myosin filaments, enhancing myocardial contractility.
In overdose, the electrolyte shift becomes pathological: intracellular potassium concentration decreases and calcium levels rise sharply, impairing the electrical stability of cardiomyocytes.
Typical ST-segment and T-wave changes
The main and most recognizable ECG sign of glycoside saturation and overdose is scooping ST-segment depression below the isoelectric line. The shape of the displacement resembles a scoop or boat: a smooth downward transition from the R wave, a concave lower part, and an upward slope toward the T wave.
- Scooping ST depression is the pathognomonic pattern of the "digitalis effect".
- Biphasic or negative asymmetric T wave in leads with a tall R wave (most commonly V5–V6, I, II).
- Moderate shortening of the QT interval is possible due to accelerated repolarization caused by intracellular calcium overload.
These changes reflect the phenomenon of glycoside saturation and do not always indicate toxicity on their own — their combination with arrhythmias points to an overdose.
Rhythm and conduction disorders
The combination of intracellular hypokalemic shift and calcium overload increases ventricular myocardial excitability while simultaneously depressing sinus node automaticity and AV nodal conduction. This explains the characteristic "dual" arrhythmogenic face of digitalis toxicity: ventricular ectopic activity against the background of bradycardia and AV block.
The following disorders are most frequently observed in overdose:
- Ventricular extrasystole is the most frequent arrhythmia, registered in approximately 70% of cases, often in the form of bigeminy or multiform extrasystoles.
- Atrial extrasystole and atrial fibrillation with a slow ventricular response — about 10–15%.
- Sinus bradycardia and AV blocks of varying degrees due to depression of SA node automaticity and AV node conduction.
- Bundle branch blocks are relatively rare (about 2%).
- In the most severe cases — asystole and ventricular fibrillation.
ECG analysis in digitalis toxicity
When evaluating an ECG in a patient taking glycosides, one should sequentially look for the characteristic set of signs:
- Evaluate the ST segment in leads with a dominant R wave — presence of scooping depression.
- Analyze the T-wave morphology — biphasic or negative with an asymmetric contour.
- Measure the PQ and QT intervals — PQ prolongation indicates AV block, while QT shortening is typical of the glycoside effect.
- Identify ectopic complexes, evaluate their morphology and frequency.
- Assess the baseline rhythm — sinus, bradycardia, atrial fibrillation with a slow ventricular response.
Differential diagnosis
Scooping ST depression and T-wave inversion require differential diagnosis with myocardial ischemia and non-ST-segment elevation myocardial infarction. Unlike ischemic changes, digitalis depression has a characteristic concave shape, is usually recorded in multiple leads with a tall R wave, and is combined with QT shortening. Ischemic depression is more often horizontal or downsloping, accompanied by a symmetric negative T wave and QT prolongation.
Clinical data are also taken into account: drug intake, plasma digoxin concentration, potassium and magnesium levels, concomitant renal failure, dyspeptic and neurological manifestations of toxicity.
Key points
- Cardiac glycosides inhibit Na⁺/K⁺-ATPase and secondarily the Na⁺/Ca²⁺ exchanger, increasing intracellular calcium.
- The main ECG sign of saturation is scooping ST-segment depression.
- A biphasic or negative asymmetric T wave and shortening of the QT interval are characteristic.
- The most frequent arrhythmia in overdose is ventricular extrasystole (about 70%).
- Atrial fibrillation with a slow response, sinus bradycardia, and AV blocks are also typical.
- Severe toxicity can lead to ventricular fibrillation and asystole.
- Differential diagnosis is performed with myocardial ischemia: the shape of the depression, QT duration, and clinical presentation are taken into account.
- ECG evaluation is supplemented by determining plasma levels of digoxin, potassium, and magnesium.