Why Digoxin Causes ST Depression
Digoxin causes ST depression through its direct electrophysiologic effects on cardiac cells by inhibiting sodium-potassium (Na-K) ATPase, which alters the normal repolarization pattern of the ventricles, producing characteristic downsloping or "scooped" ST segment depression that is a normal pharmacologic effect of the drug, not a sign of toxicity or myocardial ischemia. 1
Mechanism of ST Depression
Direct Electrophysiologic Effects
Digoxin inhibits Na-K ATPase in cardiac myocytes, leading to increased intracellular calcium and altered cellular repolarization patterns that manifest as ST segment changes on the ECG 2, 3
The ST depression is an expected pharmacologic effect of therapeutic digoxin doses and reflects the drug's action on cardiac tissue, not toxicity 1
The FDA drug label explicitly states: "The use of therapeutic doses of digoxin may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. These electrophysiologic effects reflect an expected effect of the drug and are not indicative of toxicity." 1
Clinical Characteristics of Digoxin-Induced ST Depression
Pattern and Timing
ST depression occurs at rest and during exercise in patients taking digoxin, with the most pronounced changes typically occurring at heart rates of 110-130 beats/min 4
The ST changes are dose-dependent and can occur even at low therapeutic doses (as low as 2.4 μg/kg body weight) 4
The depression is numerically small but statistically significant, appearing as a characteristic "scooped" or downsloping pattern 4, 5
Important Clinical Distinction
This ST depression does NOT indicate myocardial ischemia or coronary insufficiency 1, 4, 6
The pattern differs from ischemic ST depression: during recovery after exercise, digoxin-induced ST changes resolve quickly (within the first minutes), unlike ischemic changes which typically persist 4
Digoxin produces false-positive ST depression during both exercise stress testing and ambulatory ECG monitoring, occurring in approximately 20-26% of healthy subjects 5
Critical Clinical Pitfalls
Misinterpretation as Ischemia
Only about one-third of healthy persons on digoxin will show ST depression that could be mistaken for coronary insufficiency 6
Digoxin may produce false positive ST-T changes during exercise testing, which can lead to unnecessary cardiac workup if not recognized 1
The ST depression can occur at heart rates lower than those achieved during stress testing, making ambulatory monitoring less useful for detecting true coronary disease in digitalized patients 5
When to Suspect True Toxicity vs. Normal Effect
ST depression alone is NOT a sign of digoxin toxicity - it's a normal effect at therapeutic levels 1
True digoxin toxicity manifests as cardiac arrhythmias (heart block, ventricular ectopy, atrial tachycardia with block) rather than simple ST depression 1
Toxicity is commonly associated with serum levels >2 ng/mL but may occur at lower levels with hypokalemia, hypomagnesemia, or hypothyroidism 7
Practical Management Considerations
For Diagnostic Testing
If evaluating for coronary artery disease in a patient on digoxin, consider discontinuing digoxin for 14 days before exercise testing to avoid false-positive results 4, 6
However, if urgent evaluation is needed, an initial stress test can be performed while on digoxin, recognizing that only one-third will show false-positive changes; if significant ST depression occurs, repeat testing after a digoxin-free interval 6
Monitoring Approach
Serial ECG monitoring for ST depression is unnecessary in stable patients on therapeutic digoxin doses 1
Focus monitoring on heart rate, rhythm disturbances, and symptoms rather than ST segment changes 1, 7
The characteristic "digitalis effect" on ECG (PR prolongation and ST depression) should be documented as a baseline finding, not as an adverse event 1