Cardiac arrhythmias due to digoxin toxicity
- Ary L Goldberger, MD
Ary L Goldberger, MD
- Section Editor — Electrocardiography
- Professor of Medicine
- Harvard Medical School
Cardiac glycosides (digitalis preparations including digoxin and digitoxin) are used clinically in two situations: heart failure due to systolic dysfunction, and in certain supraventricular tachyarrhythmias :
●The ability to enhance cardiac contractility and modulate neurohumoral activation can lead to symptomatic improvement in systolic heart failure, although it is unclear if survival is prolonged. (See "Use of digoxin in heart failure with reduced ejection fraction".)
●Digoxin also slows conduction through the atrioventricular (AV) junction (node) by increasing vagal tone. It may also have a sympathoinhibitory effect in therapeutic doses. As a result, it is sometimes used (usually adjunctively with beta blockers or calcium channel blockers) for controlling the ventricular response in atrial fibrillation and atrial flutter when there is excessively rapid transmission of stimuli from the atria to the ventricles through the AV junction. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy" and "Control of ventricular rate in atrial flutter".)
●Digoxin may also be effective in the treatment of certain types of reentrant paroxysmal supraventricular tachycardia involving the AV node.
Digoxin toxicity continues to be an important clinical problem which may be life-threatening . The incidence of digoxin excess and toxicity, along with the potential associated arrhythmias, are presented here. The management of digoxin intoxication, including the treatment of cardiac arrhythmias associated with digoxin toxicity, is discussed separately. (See "Digitalis (cardiac glycoside) poisoning" and "Cardioversion for specific arrhythmias", section on 'Cardioversion in patients with digitalis toxicity'.)
- Gheorghiade M, Adams KF Jr, Colucci WS. Digoxin in the management of cardiovascular disorders. Circulation 2004; 109:2959.
- Hauptman PJ, Kelly RA. Digitalis. Circulation 1999; 99:1265.
- Hussain Z, Swindle J, Hauptman PJ. Digoxin use and digoxin toxicity in the post-DIG trial era. J Card Fail 2006; 12:343.
- Mahdyoon H, Battilana G, Rosman H, et al. The evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. Am Heart J 1990; 120:1189.
- Williamson KM, Thrasher KA, Fulton KB, et al. Digoxin toxicity: an evaluation in current clinical practice. Arch Intern Med 1998; 158:2444.
- See I, Shehab N, Kegler SR, et al. Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005 to 2010. Circ Heart Fail 2014; 7:28.
- Adams KF Jr, Patterson JH, Gattis WA, et al. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis. J Am Coll Cardiol 2005; 46:497.
- Ahmed A, Pitt B, Rahimtoola SH, et al. Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial. Int J Cardiol 2008; 123:138.
- Goldberger ZD, Goldberger AL. Therapeutic ranges of serum digoxin concentrations in patients with heart failure. Am J Cardiol 2012; 109:1818.
- Washam JB, Stevens SR, Lokhnygina Y, et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Lancet 2015; 385:2363.
- Allen LA, Fonarow GC, Simon DN, et al. Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial Fibrillation Cohort. J Am Coll Cardiol 2015; 65:2691.
- Kelly RA, Smith TW. Recognition and management of digitalis toxicity. Am J Cardiol 1992; 69:108G.
- Eisner DA, Smith TW. The Na-K pump and its effectors in cardiac muscle. In: The Heart and Cardiovascular System, Fozzard HA, Haber E, Katz AM, Morgan HE (Eds), Raven Press, New York 1991. p.863.
- Santana LF, Gómez AM, Lederer WJ. Ca2+ flux through promiscuous cardiac Na+ channels: slip-mode conductance. Science 1998; 279:1027.
- Sagawa T, Sagawa K, Kelly JE, et al. Activation of cardiac ryanodine receptors by cardiac glycosides. Am J Physiol Heart Circ Physiol 2002; 282:H1118.
- Watanabe AM. Digitalis and the autonomic nervous system. J Am Coll Cardiol 1985; 5:35A.
- Matsumori A, Igata H, Ono K, et al. High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity. Jpn Circ J 1999; 63:934.
- Toda N, West TC. The influence of ouabain on cholinergic responses in the sinoatrial node. J Pharmacol Exp Ther 1966; 153:104.
- Goodman DJ, Rossen RM, Ingham R, et al. Sinus node function in the denervated human heart. Effect of digitalis. Br Heart J 1975; 37:612.
- Smith TW, Antman EM, Friedman PL, et al. Digitalis glycosides: mechanisms and manifestations of toxicity. Part I. Prog Cardiovasc Dis 1984; 26:413.
- Smith TW, Antman EM, Friedman PL, et al. Digitalis glycosides: mechanisms and manifestations of toxicity. Part II. Prog Cardiovasc Dis 1984; 26:495.
- Reiffel JA, Bigger JT Jr, Cramer M. Effects of digoxin on sinus nodal function before and after vagal blockade in patients with sinus nodal dysfunction: a clue to the mechanisms of the action of digitalis on the sinus node. Am J Cardiol 1979; 43:983.
- VASSALLE M, GREENSPAN K, HOFFMAN BF. AN ANALYSIS OF ARRHYTHMIAS INDUCED BY OUABAIN IN INTACT DOGS. Circ Res 1963; 13:132.
- JAMES TN, NADEAU RA. The chronotropic effect of digitalis studied by direct perfusion of the sinus node. J Pharmacol Exp Ther 1963; 139:42.
- Scherlag BJ, Abelleira JL, Narula OS, Samet P. The differential effects of ouabain on sinus, A-V nodal, His bundle, and idioventricular rhythms. Am Heart J 1971; 81:227.
- MENDEZ C, ACEVES J, MENDEZ R. Inhibition of adrenergic cardiac acceleration by cardiac glycosides. J Pharmacol Exp Ther 1961; 131:191.
- Steinbeck G, Bonke FI, Allessie MA, Lammers WJ. The effect of ouabain on the isolated sinus node preparation of the rabbit studied with microelectrodes. Circ Res 1980; 46:406.
- Takayanagi K, Jalife J. Effects of digitalis intoxication on pacemaker rhythm and synchronization in rabbit sinus node. Am J Physiol 1986; 250:H567.
- Geer MR, Wagner GS, Waxman M, Wallace AG. Chronotropic effect of acetylstrophanthidin infusion into the canine sinus nodal artery. Am J Cardiol 1977; 39:684.
- Gorgels APM, Vos MA, Smeets JLRM, et al. Delayed afterdepolarizations and atrial and ventricular arrhythmias. In: Cardiac Electrophysiology: A Textbook, Rosen MR, Janse MJ, Wit AL (Eds), Futura Publishing, Mount Kisco 1990. p.341.
- Kastor JA, Yurchak PM. Recognition of digitalis intoxication in the presence of atrial fibrillation. Ann Intern Med 1967; 67:1045.
- Carleton RA, Miller PH, Graettinger JS. Effects of ouabain, atropine, and ouabain and atropine on A-V nodal conduction in man. Circ Res 1967; 20:283.
- Toda N, West TC. The action of ouabain on the function of the atrioventricular node in rabbits. J Pharmacol Exp Ther 1969; 169:287.
- Goodman DJ, Rossen RM, Cannom DS, et al. Effect of digoxin on atioventricular conduction. Studies in patients with and without cardiac autonomic innervation. Circulation 1975; 51:251.
- Ricci DR, Orlick AE, Reitz BA, et al. Depressant effect of digoxin on atrioventricular conduction in man. Circulation 1978; 57:898.
- Childers R. Classification of cardiac dysrhythmias. Med Clin North Am 1976; 60:3.
- Fisch C, Knoebel SB. Digitalis cardiotoxicity. J Am Coll Cardiol 1985; 5:91A.
- Kleiger R, Lown B. Cardioversion and digitalis. II. Clinical studies. Circulation 1966; 33:878.
- Morris SN, Zipes DP. His bundle electrocardiography during bidirectional tachycardia. Circulation 1973; 48:32.
- Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106:69.
- INCIDENCE OF DIGOXIN TOXICITY
- PLASMA DIGOXIN LEVELS ASSOCIATED WITH TOXICITY
- MECHANISMS OF CARDIAC TOXICITY
- DIGOXIN-INDUCED ARRHYTHMIAS
- Sinus bradycardia, tachycardia, block, and arrest
- Ectopic atrial tachycardia with block
- Atrial fibrillation and flutter
- AV nodal block
- Junctional rhythm, tachycardia, and bradycardia
- Ventricular arrhythmias
- - Ventricular premature beats
- - Ventricular tachycardia
- - Ventricular fibrillation
- - Bidirectional ventricular tachycardia