Current Cardiology Reports

, Volume 1, Issue 4, pp 289–296 | Cite as

Proarrhythmia, a serious complication of antiarrhythmic drugs

  • Philip J. Podrid
Article

Abstract

Aggravation of arrhythmia with antiarrhythmic drugs is not an infrequent side effect associated with antiarrhythmic drugs. Defined as the provocation of a new arrhythmia or a significant increase in the frequency of a preexisting arrhythmia, it occurs with all antiarrhythmic agents, although the incidence varies from 6% to 23% with the different drugs. In general, arrhythmia aggravation is an early event, occurring within the first several days of initiating drugs therapy. It has been found, however, that this complication can also occur as a late event, particularly in patients who have evidence of ongoing ischemia that may be overt or silent. Although there is no good way to predict the patient who is likely to experience this complication, it has been observed that there several predictors of an increased risk for experiencing arrhythmia aggravation including significant underlying heart disease, congestive heart failure, evidence of active or potentially active ischemia, and electrolyte abnormalities, particularly hypokalemia.

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References and Recommended Reading

  1. 1.
    Velebit V, Podrid PJ, Cohen B, et al.: Aggravation and provocation of ventricular arrhythmia by antiarrhythmic drugs Circulation 1982, 65:886–894.PubMedGoogle Scholar
  2. 2.
    Keren A, Tzivoni D, Gavish D, et al.: Etiology warning signs and therapy of torsade de pointes Ñ a study of ten patients. Circulation 1981, 64:1167–1174.PubMedGoogle Scholar
  3. 3.
    Zipes, DP. Proarrhythmic effects of antiarrhythmic drugs. Am J Cardiol 1987, 59:26E-31E.PubMedCrossRefGoogle Scholar
  4. 4.
    Morganroth J, Horowitz LN: Flecainide - Its proarrhythmic effect and expected changes on the surface electrocardiogram. Am J Cardiol 1984, 53:89B-94B.PubMedCrossRefGoogle Scholar
  5. 5.
    Minardo JD, Heger JJ, Miles et al.: Clinical characteristics of patients with ventricular fibrillation during antiarrhythmic drug therapy. N Engl J Med 1988, 319:257–262.PubMedCrossRefGoogle Scholar
  6. 6.
    Echt DS, Liebson PR, Mitchell LB, et al.: Mortality and morbidity in patients receiving encainide, flecainide or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991, 324 781–788.PubMedCrossRefGoogle Scholar
  7. 7.
    Podrid, PJ, Lambert S, Graboys TB, et al.: Aggravation of arrhythmia by antiarrhythmic drugs: Incidence and predictors. Am J Cardiol 1987, 59:38E-44E.PubMedCrossRefGoogle Scholar
  8. 8.
    Stanton MS, Prystowsky EN, Fineberg NS, et al.: Arrhythmogenic effects of antiarrhythmic drugs: A study of 506 patients treated for VT or fibrillation. J Am Coll Cardiol 1989, 14:209–215.PubMedCrossRefGoogle Scholar
  9. 9.
    Poser R, Podrid PJ, Lombardi F, Lown, B: Aggravation of arrhythmia induced with antiarrhythmic drugs during electrophysiologic testing. Am Heart J 1985, 110:9–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Rinkenberger RL, Prystowsky EN, Jackman WN, et al.: Drug conversion of nonsustained VT to sustained VT during serial electrophysiologic studies; Identification of drugs that exacerbate tachycardia and potential mechanisms. Am Heart J 1982, 103:177–184.PubMedCrossRefGoogle Scholar
  11. 11.
    Horowitz LN, Greenspan AM, Rae AP, et al.: Proarrhythmic responses during electrophysiologic testing. Am J Cardiol 1987, 59:45E-48E.PubMedCrossRefGoogle Scholar
  12. 12.
    Rae AP, Kay HR, Horowitz LN, et al.: Proarrhythmic effects of antiarrhythmic drugs in patients with malignant ventricular arrhythmia evaluated by electrophysiologic testing. J Am Coll Cardiol 1988, 12:131–139PubMedCrossRefGoogle Scholar
  13. 13.
    Au PK, Bhandari AK, Bream R, et al.: Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without VT. J Am Coll Cardiol 1987, 9:389–397.PubMedCrossRefGoogle Scholar
  14. 14.
    Ranger S, Talajic M, Lemerey R, et al.: Amplification of flecainide induced ventricular conduction during flecainide therapy. Circulation 1989, 79:1000–1006.PubMedGoogle Scholar
  15. 15.
    McKibbin JW, Pocock N, Barlow JM, et al.: Sotalol, hypokalemia syncope and torsade de pointes. Br Heart J 1984, 51:157–162.PubMedGoogle Scholar
  16. 16.
    Kuck KH, Kunze KP, Bleifeld W: Sotalol-induced torsad de pointes. Am Heart J 1984, 107:179–180.PubMedCrossRefGoogle Scholar
  17. 17.
    Jackman WM, Friday KJ, Anderson JL, Aliot, EM: The long QT syndromes: A critical review, new clinical observations and unifying hypothesis. Prog Cardiovasc Dis 1988, 31:115–172.PubMedCrossRefGoogle Scholar
  18. 18.
    Roden DM: Taking the “idio” out of “idiosyncratic”: Predicting torsades de pointes. Pacing Clin Electrophysiol 1998, 21:1029–1034. In depth review of torsades de pointes, a specific type of arrhythmia aggravation presenting the known clinical risk factors for its occurrence.PubMedCrossRefGoogle Scholar
  19. 19.
    Ben-David J, Zipes D: Torsades de pointes and proarrhythmia. Lancet 1993, 341:1578–1582.PubMedCrossRefGoogle Scholar
  20. 20.
    Roden DM, Woosley RL, Primm K: Incidence of clinical features of the quinidine associated long QT syndrome. Implications for patient care. Am Heart J 1986, 111:1088–1093.PubMedCrossRefGoogle Scholar
  21. 21.
    Hondegham, LM, Snyders DJ: Class III antiarrhythmic agents have a lot of potential, but a long way to go: reduced effectiveness and dangers of reverse use-dependence. Circulation 1990, 81:686–690.Google Scholar
  22. 22.
    Meltzer RS, Robert EW, McMorrow M, Martin, RP: Atypical VT as a manifestation of disopyramide toxicity. Am J Cardiol 1978, 42 1044–1048.CrossRefGoogle Scholar
  23. 23.
    Strasberg B, Sclarovsky S, Erdberg A, et al.: Procainamide induced polymorphous VT. Am J Cardiol 1981, 47:1309–1314.PubMedCrossRefGoogle Scholar
  24. 24.
    Olshansky B, Martins J, Hunt S: N-acetyl-procainamide causing torsade de pointes. Am J Cardiol 1982, 50:1439–1441.PubMedCrossRefGoogle Scholar
  25. 25.
    Wang T, Bergstrand RM, Thompson KA, et al.: Concentrationdependent pharmacologic properties of sotalol. Am J Cardiol 1986, 57 1160–1165.PubMedCrossRefGoogle Scholar
  26. 26.
    Brown MA, Smith WM, Cubbe WF, Norris, RM: Amiodarone induced torsade de pointes. Eur Heart J 1986, 7:234–239.PubMedGoogle Scholar
  27. 27.
    Hohnloser SH, Klingenheben T, Singh, BN: Amiodaroneassociated proarrhythmic effects. A review with special reference to torsades de pointes tachycardia. Ann Intern Med 1994, 121:529–535.PubMedGoogle Scholar
  28. 28.
    Drouin E, Lande G, Charpentier F: Amiodarone reduces transmural heterogeneity of repolarization in the human heart. J Am Coll Cardiol 1998, 32 1063–1067.PubMedCrossRefGoogle Scholar
  29. 29.
    Ellenbogen KA, Stambler BS, Wood MA, et al.: Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study. J Am Coll Cardiol 1996, 28 130–136.PubMedCrossRefGoogle Scholar
  30. 30.
    Stambler BS, Wood MA, Ellenbogen KA, et al., and the Ibutilide Repeat Dose Study Investigators: Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Circulation 1996, 94:1613–1621.PubMedGoogle Scholar
  31. 31.
    Slater WS, Lampert S, Podrid PJ, Lown, B: Clinical predictors of arrhythmia worsening by antiarrhythmic drugs Am J Cardiol Coll 1988, 61:349–353.Google Scholar
  32. 32.
    Morganroth J: Risk factors for the development of proarrhythmic events. Am J Cardiol 1987, 59:32E-37E.PubMedCrossRefGoogle Scholar
  33. 33.
    Pratt, CM, Eaton, T, Frances, M, et al.: The inverse relationship between baseline left ventricular ejection fraction and outcome of antiarrhythmic drug therapy: A dangerous imbalance in the risk-benefit ratio. Am Heart J 1989, 118:433–440.PubMedCrossRefGoogle Scholar
  34. 34.
    Coggins DL, Flynn AE, Austin RE, et al.: Nonuniform loss of regional flow reserve during myocardial ischemia in dogs. Circ Res 1990, 67:253–264.PubMedGoogle Scholar
  35. 35.
    Hill JL, Gettes LS: Effect of acute coronary occlusion on local myocardial extracellular K+ activity in swine. Circulation 1980, 61:768–778PubMedGoogle Scholar
  36. 36.
    Kagiyama Y, Hill JL, Gettes LS: Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle. Circ Res 1982, 51:614–623.PubMedGoogle Scholar
  37. 37.
    Wit AL, Hoffman BF, Rosen MR: Electrophysiology and pharmacology of cardiac arrhythmias IX. Cardiac electrophysiologic effects of beta adrenergic receptor stimulation and blockade, Part A. Am Heart J 1975, 90:521–533.PubMedCrossRefGoogle Scholar
  38. 38.
    Makkar RR, Fromm BS, Steinman RT, et al.: Female gender as a risk factor for torsade de pointes associated with cardio vascular drugs. JAMA 1993, 270:2590–2597.PubMedCrossRefGoogle Scholar
  39. 39.
    Lehmann MH, Hardy S, Archibald D, et al.: Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996, 94:2534–2541.Google Scholar
  40. 40.
    Wu T-J, Ong JJC, Hwang C, et al.: Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: Role of increased fibrosis in the generation of reentry J Am Coll Cardiol 1998, 32 187–196.PubMedCrossRefGoogle Scholar
  41. 41.
    Tomaselli GF, Beukelmann DJ, Calkins HG, et al.: Sudden cardiac death in congestive heart failure: the role of abnormal repolarization. Circulation 1994, 90:2534–2539.PubMedGoogle Scholar
  42. 42.
    Dean JW, Lab MJ: Arrhythmia in heart failure: Role of mechanically induced changes in electrophysiology. Lancet 1989, 1:1309–1312.PubMedCrossRefGoogle Scholar
  43. 43.
    Reiter MJ, Landers M, Zetelaki Z, et al.: Electrophysiologic effects of acute dilatation in the isolated rabbit heart. Cycle length-dependent effects on ventricular refractoriness and conduction velocity. Circulation 1997, 96:4050–4056.PubMedGoogle Scholar
  44. 44.
    Koilpillai C, Quinones MA, Greenberg B, et al., for the SOLVD Investigators: Relation of ventricular size and function to heart failure status and ventricular dysrhythmia in patients with severe left ventricular dysfunction. Am J Cardiol 1996, 77:606–611.PubMedCrossRefGoogle Scholar
  45. 45.
    Cohn JN, Rector TS: Prognosis of congestive heart failure and predictors of mortality. Am J Cardiol 1988, 62 25A-30A.PubMedCrossRefGoogle Scholar
  46. 46.
    Packer M, Gottlieb SS, Blum MA: Immediate and long-term pathophysiologic mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure. Am J Med 1987, 82:4–10.PubMedCrossRefGoogle Scholar
  47. 47.
    Myerburg RJ, Kissler KM, Cox MM, et al.: Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride on propranolol. Circulation 1990, 80:1571–1579.Google Scholar
  48. 48.
    Bellet S, Hamden G, Somlyo A, et al.: The reversal of cardiotoxic effects of quinidine by molar sodium lactate. An experimental study. Am J Med Sci 1959, 237:165–168.PubMedCrossRefGoogle Scholar
  49. 49.
    DiSegni E, Klein HO, David D, et al.: Overdrive pacing the quinidine syncope and other long QT syndrome. Arch Intern Med 1980, 140:1036–1040.PubMedCrossRefGoogle Scholar
  50. 50.
    Tzivoni D, Banai S, Schuger C: Treatment of torsades de pointes with magnesium sulfate. Circulation 1988, 77:392–397.PubMedGoogle Scholar
  51. 51.
    Kaseda A, Gilmour RF, Zipes DP: Depressant effect of magnesium on after-depolarizations and arrhythmias induced by cesium, 4-aminopyridine or quinidine in canine Purkinje fibers. Am Heart J 1989, 118 458–466.PubMedCrossRefGoogle Scholar
  52. 52.
    Helfant RH, Scherlag BJ, Damato AN: The electrophysiologic properties of diphenylhydantoin sodium as compared to procainamide in the normal and digitalis-intoxicated heart. Circulation 1967, 38:108–118.Google Scholar
  53. 53.
    Scharmoth L: Immediate effects of intravenous propranolol on various cardiac arrhythmias. Am J Cardiol 1966, 18:438–443.CrossRefGoogle Scholar
  54. 54.
    Smith TW, Haber E, Yeatman L, Butler, VP: Reversal of advanced digoxin intoxication with Fab fragments of digoxin specific antibodies. N Engl J Med 1976, 294:797–800.PubMedCrossRefGoogle Scholar
  55. 55.
    Antman EM, Wenger TL, Butler VP, et al.: Treatment of 150 cases of life-threatening digitalis intoxication with digoxinspecific Fab antibody fragments. Final report of a multicenter study. Circulation 1990, 81:1744–1752.PubMedGoogle Scholar

Copyright information

© Current Science Inc 1999

Authors and Affiliations

  • Philip J. Podrid
    • 1
  1. 1.Section of CardiologyBoston Medical CenterBostonUSA

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