Special Feature
Digoxin Effect on the Electrocardiogram
By Richard A. Harrigan, MD, FAAEM
Much has been written about the therapeutic and toxicologic effects of digoxin (and other digitalis preparations) regarding both the clinical and electrocardiographic manifestations. The electrocardiographic effects associated with digoxin toxicity recently were reviewed in the emergency medicine literature.1 Less attention has been given to the effect of digoxin—whether in therapeutic or non-toxic situations—on the electrocardiogram (ECG), even though these manifestations are likely to be seen more often by the practicing emergency physician. After a brief review of the pharmacologic effects of digoxin on the heart, the ECG manifestations known as "digoxin effect" or "digitalis effect" will be described. Differential diagnostic possibilities will be presented for these varied electrocardiographic effects.
Pharmacology
Digitalis preparations act by inhibiting the sodium-potassium ATPase pump, thereby increasing intracellular calcium levels.1 The effect of the drug is largely mediated by the autonomic nervous system, enhancing vagal tone both centrally and peripherally. This leads to a diminished sinus node discharge rate, shortened atrial refractoriness, and prolonged refractoriness of the atrioventricular (AV) node.2 Parasympathetic mediation of effect is evidenced by the fact that digoxin effects on rate control in atrial fibrillation (a common usage) are not uniform, even in the same person. For instance, when at rest, in a state of vagal tone predominance, the ventricular rate usually is maintained in the desired range (60-100 bpm). However, when the patient with atrial fibrillation exercises—thereby decreasing vagal tone and increasing adrenergic tone—digoxin is less successful for maintaining rate control due to a diminished effect on the AV node. Thus, digoxin rarely is used as a single agent to control the ventricular rate in atrial fibrillation.2
Digoxin Effect on the ECG
"Drug effects" on the ECG are distinguished from "drug toxicity" in that the former term encompasses all of the effects seen during therapeutic use of the agent. Of course, this is not to say that these drug effects disappear in poisoning situations; rather, they may be joined by the various manifestations of the toxic effect of the drug. (See Figure.)
| Figure: Digoxin Effect . . . and More |
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On this ECG, the characteristic "coving" ST-segment depression of digoxin effect is seen, especially in leads V3-V5. The QT interval does appear short, especially for the relatively slow ventricular rate. Coincidentally, this patient also suffered from digoxin toxicity, as evidenced by third-degree AV block (complete heart block). The third QRS complex is a junctional extrasystole, and accounts for the seeming irregularity of the rhythm (the RR intervals between beats 1 and 2, and between beats 4 and 5, are actually the same). Once again, digoxin effect is a drug effect seen at therapeutic levels, and is independent of digoxin toxicity. |
Clinical digoxin toxicity, manifested by gastrointestinal, central nervous system, and electrophysiologic changes, may occur in the absence of the drug effect ("digoxin effect") on the ECG. Conversely, prominent changes consistent with digoxin effect may occur with therapeutic or subtherapeutic levels of the drug, in the absence of clinical toxicity.
Morphologic effects. The principal effect classically associated with therapeutic digoxin use is a "coving" or "scooped" depression of the ST segment; this "sagging" typically demonstrates an upward concavity. (See Table 1.)
| Table 1: Summary of Principal Digoxin Effects on the ECG | |
| • ST segment depression | |
| - "Coving" or "scooped" morphology | |
| - Concave upward | |
| • T wave changes | |
| - Decreased amplitude; flattening | |
| - Inversion | |
| - Biphasic | |
| • QT interval shortening | |
| • Prominent U waves | |
| • PR segment lengthening (may be minor) | |
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This finding is more prominently seen in leads featuring a tall R wave. (See Figure.) At times, J-point depression is seen, and it may be difficult to distinguish this from the ST segment depression associated with myocardial ischemia.3-5 The depressed ST segment may seem to pull the T wave downward, resulting in a biphasic T wave, with the first portion being negative. (See Figure, especially leads V3-V5.)
In some instances, coving ST segment depression is not seen, and ST segment changes may mimic those seen with the strain pattern of ventricular hypertrophy, with a slight upward convexity of the ST segment.5 Normal subjects orally loaded with digoxin over six weeks were found to have a dose-dependent depression of the ST segment on ECG; this finding was most accentuated at mildly tachycardic rates during exercise (110-130 bpm); higher rates did not increase the amount of ST depression. This finding is in contradistinction to the ST segment depression typically seen in exercise-induced ischemia, wherein higher rates correspond to further depression of the ST segment.6 Nonetheless, digoxin effect may result in false-positive stress test results.3
Perhaps the earliest, but most variable, features of digoxin effect on the ECG are the changes in T wave morphology. The T waves may be flattened, inverted, biphasic, or of course, may remain normal; biphasic T waves may demonstrate peaking of the terminal portion.7 T wave inversion associated with digoxin effect is characteristically asymmetric, with symmetric inversions of the T wave being more typical of such entities as myocardial ischemia or central nervous system disorder.8 Prominence of the U wave also may be seen with therapeutic levels of digoxin; this is usually best seen in the mid-precordial leads, and is not as profound as that typically associated with hypokalemia.5
ECG interval effects. The QT interval is generally known to vary with rate (inversely) and age (directly), and is usually slightly longer in women than in men.4,5 Whereas there are many diseases and medications that cause prolongation of the QT interval, digoxin is on the short list of things that cause a shortened QT interval. (Hypercalcemia is another recognized cause, as well as early phase hyperkalemia—when T waves are narrowing and peaking.)3-5,8 Two major ECG texts3,4 do not describe a lower limit of normal for the QT interval, whereas another5 states that the lower limit of normal (for rates of 45-115 bpm) is 0.30 seconds. Vagally-mediated slowing of AV nodal conduction manifests as a slight increase of the PR interval for those individuals in sinus rhythm.4,5
| Table 2: Differential Diagnosis of ST Segment Depression on the ECG3 | |||
| • | Subendocardial ischemia | • | Digoxin effect |
| • | Ventricular hypertrophy | • | Bundle branch block |
| • | Ventricular paced rhythm | • | Hypokalemia |
| • | Hyperventilation | ||
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Summary
Digoxin effect on the ECG is independent of the ECG changes seen in toxicity with this agent. With digoxin effect, changes in wave morphology as well as interval duration may be seen. Effects of the drug on repolarization (an enhanced recovery phase) are responsible for the ST segment, QT interval, and T wave changes associated with digoxin in therapeutic situations.5 Vagal effects of the drug primarily are responsible for the slight slowing of the sinus rate and increase in AV conduction time (i.e., prolongation of the PR interval) seen in therapeutic dosing of digoxin, but direct effects of the drug also seem to play a role.5
References
1. Ma G, et al. Electrocardiographic manifestations: Digitalis toxicity. J Emerg Med 2001;20:145-152.
2. Miller JM, Zipes DP. Management of the patient with cardiac arrhythmias. In: Heart Disease: A Textbook of Cardiovascular Medicine. 6th Ed. Philadelphia: WB Saunders; 2001:700-774.
3. Mirvis DM, Goldberger AL. Electrocardiography. In: Heart Disease: A Textbook of Cardiovascular Medicine. 6th Ed. Philadelphia: WB Saunders; 2001:82-125.
4. Wagner GS. Marriott’s Practical Electrocardiography. 10th Ed. Philadelphia: Lippincott, Williams, and Wilkins; 2001:229-230.
5. Chou T. Electrocardiography in Clinical Practice: Adult and Pediatric. 4th Ed. Philadelphia: WB Saunders; 1996:503-504.
6. Sundqvist K, et al. Effect of digoxin on the electrocardiogram at rest and during exercise in healthy subjects. Am J Cardiol 1986;57:661-665.
7. Levine HD, Angelakos ET. Late peaking of the T wave as a digitalis effect. Am Heart J 1964;68:320-326.
8. Walder LA, Spodick DH. Global T wave inversion. J Am Coll Cardiol 1991;17:1479-1485.
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