Abstract
Background: Studies of healthy volunteers or patients in sinus rhythm have indicated that treatment with digoxin produces characteristic changes in the electrocardiogram (ECG). No randomized, placebo‐controlled studies are available and no study has investigated the effect on ECG in patients with atrial fibrillation.
Hypothesis: In a substudy to a trial comparing the therapeutic effect of intravenously administered digoxin with placebo in patients with acute atrial fibrillation, we investigated these effects as well as the relation between ECG changes and serum concentration of digoxin.
Methods: In all, 167 patients were included. Standard ECGs recorded at baseline, and at 2,6,12, and 16 h after randomization were digitized, and changes in RR‐intervals, QRS width, ST‐segment amplitude at 60 ms after the J point, T‐wave amplitude, and QTc interval were calculated. Furthermore, the correlation between the serum concentration of digoxin at 16 h after inclusion and changes on the ECG was analyzed.
Results: Compared with placebo, digoxin resulted in an increase in RR‐interval (p < 0.0001), a decrease in ST‐segment and T‐wave amplitude (p = 0.009 and p = 0.002, respectively), and in the QTc interval (p = 0.01). These changes were present 2 h after the first dose, but were more pronounced after 16 h. There was no significant correlation between serum concentration of digoxin and ECG changes at 16 h.
Conclusion: Compared with placebo, digoxin produces significant changes on ECG in patients with acute atrial fibrillation. The changes are in accordance with previous findings in individuals in sinus rhythm. There was no correlation between serum concentration of digoxin and ECG changes.
Keywords: digoxin, controlled clinical trial, effects on electrocardiogram
Full Text
The Full Text of this article is available as a PDF (655.8 KB).
References
- 1. Gillis RA, Quest JA: The role of the nervous system in the cardiovascular effects of digitalis. Pharmacol Rev 1980; 31: 19–97 [PubMed] [Google Scholar]
- 2. Barr I, Smith TW, Klein MD, Hagemeijer F, Lown B: Correlation of the electrophysiologic action of digoxin with serum digoxin concentration. J Pharmacol Exp Therapeut 1972; 180: 710–722 [PubMed] [Google Scholar]
- 3. Cohn AE, Fraser FR, Jamieson RA: The influence of digitalis on the T wave of the human ECG. J Exp Med 1915; 21: 592–604 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Pardee HEB: The standardization of digitalis by its action on the human heart. J Am Med Assoc 1923; 81: 186–188 [Google Scholar]
- 5. Gold H, Kwit NT, Cattell MK: Studies on purified digitalis glucosides. I. Potency and dosage of “digitaline nativelle” by oral administration in men. J Pharmacol Exp Therapeut 1940; 69: 177–197 [Google Scholar]
- 6. Hirsch EZ: The effects of digoxin on the electrocardiogram after strenuous exercise in normal men. Am Heart J 1965; 70: 196–203 [DOI] [PubMed] [Google Scholar]
- 7. Nordström‐Öhrberg G: Effects of digitalis glucosides on electrocardiogram and exercise test in healthy subjects. Thesis. Stockholm (1964) [PubMed]
- 8. Joubert PH, Kroening B, Weintraub M: Serial serum digoxin concentrations and quantitative electrocardiographic changes. Clin Pharmacol Therapeut 1975; 18: 757–760 [DOI] [PubMed] [Google Scholar]
- 9. Joubert PH, Müller FO, Pansegrouw DF, Kleynhans PHT: A correlative study of serum digoxin levels and electrocardiographic measurements. S Afr J Med 1975; 49: 1177–1181 [PubMed] [Google Scholar]
- 10. LeWinter MM, Crawford MH, O'Rourke RA, Karliner JS: The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram. Am Heart J 1977; 93: 202–209 [DOI] [PubMed] [Google Scholar]
- 11. Sundqvist K, Atterhög J‐H, Jogestrand T: Effect of digoxin on the electrocardiogram at rest and during exercise in healthy subjects. Am J Cardiol 1986; 57: 661–665 [DOI] [PubMed] [Google Scholar]
- 12. Sundqvist K, Jogestrand T: Effect of autonomic blockade on digoxin‐induced ECG changes at rest and during exercise in healthy subjects. J Electrocardiol 1993; 26: 219–223 [DOI] [PubMed] [Google Scholar]
- 13. Frick MH, Vitanen K, Sävelä J: Modification of digitalis‐induced electrocardiographic changes by propranolol and potassium. Ann Clin Res 1972; 4: 213–218 [PubMed] [Google Scholar]
- 14. Saner HE, Lange HW, Pierach MD, Aeppli DM: Relation between serum digoxin concentration and the electrocardiogram. Clin Cardiol 1988; 11: 752–756 [DOI] [PubMed] [Google Scholar]
- 15. Redfors A: Plasma digoxin concentration—its relation to digoxin dosage and clinical effects in patients with atrial fibrillation. Br Heart J 1972; 34: 383–391 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Chamberlain DA, White RJ, Howard MR, Smith TW: Plasma digoxin concentration in patients with atrial fibrillation. Br Med J 1970; 3: 429–432 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group : Intravenous digoxin in acute atrial fibrillation. Results of a randomised, placebo‐controlled multicentre trial in 239 patients. Eur Heart J 1997; 18: 649–654 [DOI] [PubMed] [Google Scholar]
- 18. Taran LM, Szilagyi N: The duration of the electrical systole (Q‐T) in acute rheumatic carditis in children. Am Heart J 1947; 33: 14–26 [DOI] [PubMed] [Google Scholar]
- 19. Smit AJ, Scaf AHJ, van Essen LH, Lie KI, Wesseling H: Digoxin infusion versus bolus injection in rapid atrial fibrillation: Relation between serum level and response. Eur J Clin Pharmacol 1990; 38: 335–341 [DOI] [PubMed] [Google Scholar]
- 20. Kramer WG, Kolibash AJ, Lewis RP, Bathala MS, Visconti JA, Reuning RH: Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man. J Pharmacokin Biopharmaceut 1979; 7: 47–61 [DOI] [PubMed] [Google Scholar]