Drug Safety

, Volume 20, Issue 1, pp 85–94 | Cite as

Treatment of Cardiac Arrhythmias During Pregnancy

Safety Considerations
  • Jose A. Joglar
  • Richard L. Page
Practical Drug Safety


Maternal and fetal arrhythmias occurring during pregnancy may jeopardise the life of the mother and the fetus. When arrhythmias are well tolerated and patients are minimally symptomatic, conservative therapy, such as observation and rest or vagal manoeuvres, should be employed. When arrhythmias cause debilitating symptoms or haemodynamic compromise, antiarrhythmic drug therapy is indicated. Although no antiarrhythmic drug is completely safe during pregnancy, most are well tolerated and can be given with relatively low risk.

Physiological changes that occur during pregnancy mandate caution when administering antiarrhythmic drugs, with close monitoring of serum concentration and patient response. Drug therapy should be avoided during the first trimester of pregnancy if possible, and drugs with the longest record of safety should be used as first-line therapy.

Several therapeutic options exist for most arrhythmias in the mother and fetus. Of the class IA agents, quinidine has the longest record of safety during pregnancy, and is generally well tolerated. Procainamide is also well tolerated, and should be a first line option for acute treatment of undiagnosed wide complex tachycardia. All IA agents should be administered in the hospital under cardiac monitoring due to the potential risk of ventricular arrhythmias (torsade de pointes).

The IB agent, lidocaine (lignocaine), has local anaesthetic role but is also generally well tolerated as an antiarrhythmic agents. Phenytoin should be avoided due to the high risk of congenital malformations and limited role as an antiar-rhythmic drug. Of the IC agents, flecainide has been shown to be very effective in treating fetal supraventricular tachycardia complicated by hydrops. β-Blockers are generally well tolerated and can be used with relative safety in pregnancy, although recent data suggest that they may cause intrauterine growth retardation if they are administered during the first trimester.

Amiodarone, a class II agents with characteristics of the other antiarrhythmic drug classes, has been reported to cause congenital abnormalities; it should be avoided during the first trimester and used only to treat life-threatening arrhythmias that fail to respond to other therapies. Adenosine is generally safe to use in pregnancy, and is the drug of choice for acute termination of maternal supraventricular tachycardia. Digoxin has a long track record of treating both maternal and fetal arrhythmias, and is one of the safest antiarrhythmics to use during pregnancy.

Direct current cardioversion to terminate maternal arrhythmias is well tolerated and effective, and should not be delayed if indicated. The use of an implantable cardioverter-defibrillator should be considered for women of childbearing potential with life-threatening ventricular arrhythmias.


Adis International Limited Digoxin Amiodarone Antiarrhythmic Drug Sotalol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Saxon LA, Perloff JK. Arrhythmias and conduction disturbances associated with pregnancy. In: Podrid PJ, Kowey PR, editors. Cardiac arrhythmia. Baltimore (MD): Williams & Wilkins, 1995: 1161–74Google Scholar
  2. 2.
    Ostrzega E, Mehra A, Widerhorn J, et al. Evidence of increased incidence of arrhythmias during pregnancy: a study of 104 pregnant women with symptoms of palpitations, dizziness or syncope [abstract]. J Am Coll Cardiol 1992; 19: 125ACrossRefGoogle Scholar
  3. 3.
    Widerhorn J, Widehorn ALM, Rahimtoola SH, et al. WPW syndrome during pregnancy: increased incidence of supraventricular arrhythmias. Am Heart J 1992; 123: 796–8PubMedCrossRefGoogle Scholar
  4. 4.
    Cox JL, Gardner MJ. Treatment of cardiac arrhythmias during pregnancy. Prog Cardiovasc Dis 1993; 36: 137–78PubMedCrossRefGoogle Scholar
  5. 5.
    Rotmensch HH, Elkayam U, Frishman W. Antiarrhythmic drug therapy during pregnancy. Ann Intern Med 1983; 98: 487–97PubMedGoogle Scholar
  6. 6.
    Berlin CM. Pharmacologic considerations of drug use in the lactating mother. Obstet Gynecol 1981; 58 Suppl.: 17s–23sPubMedGoogle Scholar
  7. 7.
    Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 1994; 93: 137–50Google Scholar
  8. 8.
    Drugs facts and comparisons. St. Louis (MO): Facts and Comparisons, 1997Google Scholar
  9. 9.
    Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol 1984; 24: 129–47PubMedGoogle Scholar
  10. 10.
    Meyer J, Lackner JE, Schochet SS. Paroxysmal tachycardia in pregnancy. Am Heart J 1931; 94: 1901–4Google Scholar
  11. 11.
    Hill LM, Malkasian GD. The use of quinidine sulfate throughout pregnancy. Obstet Gynecol 1979; 54: 366–8PubMedGoogle Scholar
  12. 12.
    Wladimiroff JW, Stewart A. Treatment of fetal cardiac arrhythmias. Br J Hosp Med 1985; 34: 134–40PubMedGoogle Scholar
  13. 13.
    Allen NM, Page RL. Procainamide administration during pregnancy. Clin Pharm 1993; 12: 58–60PubMedGoogle Scholar
  14. 14.
    Page RL. Treatment of arrhythmias during pregnancy. Am Heart J 1995; 130: 871–6PubMedCrossRefGoogle Scholar
  15. 15.
    Schnider SM. Choice of anesthesia for labor and delivery. Obstet Gynecol 1981; 58: S24–S34Google Scholar
  16. 16.
    Martin LV, Jurand A. The absence of teratogenic effects of some analgesics use in anesthesia: additional evidence from a mouse model. Anaesthesia 1992; 47: 473–6PubMedCrossRefGoogle Scholar
  17. 17.
    Brown WU, Bell GC, Alper MH. Acidosis, local anesthesia and the newborn. Obstet Gynecol 1976; 48: 27–30PubMedGoogle Scholar
  18. 18.
    Gregg AR, Tomich PG. Mexiletene use in pregnancy. J Perinatol 1988; 8: 33–5PubMedGoogle Scholar
  19. 19.
    Timmis AD, Jackson G, Holt DW. Mexiletine for control of ventricular dysrhythmias during pregnancy. Lancet 1980; II: 647–8CrossRefGoogle Scholar
  20. 20.
    Lowes HE, Ives TJ. Mexiletine use in pregnancy and lactation. Am J Obstet Gynecol 1987; 157: 446–7Google Scholar
  21. 21.
    Atkinson AJ Jr, Davison R. Diphenylhydantoin as an antiarrhythmic drug. Ann Rev Med 1974; 25: 99–113PubMedCrossRefGoogle Scholar
  22. 22.
    Hanson JW, Myrianthopoulos NC, Harvey MA, et al. Risk of the offspring of women treated with hydantoin anticonvulsants with emphasis on fetal hydantoin syndrome. J Pediatr 1976; 89: 662–8PubMedCrossRefGoogle Scholar
  23. 23.
    Echt DS, Liebson PR, Mitchel B, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. N Engl J Med 1991; 324: 781–8PubMedCrossRefGoogle Scholar
  24. 24.
    Allan LD, Chita SK, Sharland GK, et al. Flecainide in the treatment of fetal tachycardias. Br Heart J 1991; 65: 46–8PubMedCrossRefGoogle Scholar
  25. 25.
    Frohn-Mulder IM, Stewart PA, Witsenburg M, et al. The efficacy of flecainide versus digoxin in the management of fetal supaventricular tachycardia. Prenat Diagn 1995; 15: 1297–302PubMedCrossRefGoogle Scholar
  26. 26.
    Vanderhalt AL, Cocjin J, Santulli TV, et al. Conjugated hyprbilirubenemia in a newborn infant after maternal (transplacental) treatment with flecainide acetate for fetal tachycardia and fetal hydrops. J Pediatr 1995; 126: 988–90CrossRefGoogle Scholar
  27. 27.
    Capucci A, Boriani G. Propafenone in the treatment of cardiac arrhythmias. A risk-benefit appraisal. Drug Saf 1995; 12: 55–72PubMedCrossRefGoogle Scholar
  28. 28.
    Frishman WH, Chesner M. Beta-adrenergic blockers in pregnancy. Am Heart J 1988; 115: 147–52PubMedCrossRefGoogle Scholar
  29. 29.
    Pruyn SC, Phelan JP, Buchanan GC. Long-term propanolol therapy in pregnancy: maternal and fetal outcome. Am J Obstet Gynecol 1979; 135: 485–9PubMedGoogle Scholar
  30. 30.
    Rubin PC, Butters L, Clark DM, et al. Placebo-controlled trial of atenolol in treatment of pregnancy-associated hypertension. Lancet 1983; 2: 431–4Google Scholar
  31. 31.
    Wichman K, Ryulden G, Karberg BE. A placebo controlled trial of metropolol in the treatment of hypertension in pregnancy. Scand J Clin Lab Invest 1984; 169: 90–4CrossRefGoogle Scholar
  32. 32.
    Lip GYH, Beevers M, Churchill D, et al. Effect of atenolol on birth weight. Am J Cardiol 1997; 79: 1436–8PubMedCrossRefGoogle Scholar
  33. 33.
    Liedholm H, Melander A, Bitzen P-O, et al. Accumulation of atenolol and metoprolol in human breast milk. Eur J Clin Pharmacol 1971; 20: 229–31CrossRefGoogle Scholar
  34. 34.
    Delvin RG, Duchin KL, Fleiss PM. Nadolol in human serum and breast milk. Br J Clin Pharmacol 1981; 12: 393–6CrossRefGoogle Scholar
  35. 35.
    Schimimmel MS, Eldelman AJ, Wilschanski MA, et al. Toxic effects of atenolol consumed during breast feeding. J Pediatr 1989; 114: 476–8CrossRefGoogle Scholar
  36. 36.
    Widerhorn J, Bhandari AK, Bughi S, et al. Fetal and neonatal adverse effects profile of amiodarone treatment during pregnancy. Am Heart J 1991; 22: 1162–5CrossRefGoogle Scholar
  37. 37.
    De Wolf D, De Schepper J, Verhaaren H, et al. Congenital hypothyroid goiter and amiodarone. Acta Paediatr Scand 1988; 77: 616–8PubMedCrossRefGoogle Scholar
  38. 38.
    Magee LA, Downar E, Sermer M, et al. Pregnancy outcome after gestational exposure to amiodarone in canada. Am J Obstet Gynecol 1995; 172: 1307–11PubMedCrossRefGoogle Scholar
  39. 39.
    Ovadia M, Mitermayer B, Gifford L, et al. Human experience with amiodarone in the embrionic period. Am J Cardiol 1994; 73: 316–7PubMedCrossRefGoogle Scholar
  40. 40.
    Strunge P, Frandsen J, Andeasen F. Amiodarone during pregnancy. Eur Heart J 1988; 9: 106–9PubMedGoogle Scholar
  41. 41.
    McKenna WJ, Harris L, Rowland E, et al. Amiodarone therapy during pregnancy. Am J Cardiol 1983; 51: 1231–3PubMedCrossRefGoogle Scholar
  42. 42.
    Anderson, JL. Sotalol, bretylium, and other class 3 antiarrhythmics. In: Podrid PJ, Kowey PR, editors. Cardiac arrhythmia. Baltimore: Williams & Wilkins, 1995: 450-66Google Scholar
  43. 43.
    O’Hare MF, Murnaghan GA, Russell CJ, et al. Sotalol as a hypotensive agent in pregnancy. Br J Obstet Gynaecol 1980; 87: 814–20PubMedCrossRefGoogle Scholar
  44. 44.
    Wagner X, Jouglard J, Moulin M, et al. Coadministration of flecainide acetate and sotalol during pregnancy: lack of teratogenic effects, passage across the placenta, and excretion in human milk. Am Heart J 1990; 119: 700–2PubMedCrossRefGoogle Scholar
  45. 45.
    Kowey PR, Vander Lugt JT, Luderer JR. Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation/flutter. Am J Cardiol 1996; 78(8a): 46–52PubMedCrossRefGoogle Scholar
  46. 46.
    Bryerly WG, Hartmann A, Foster DE, et al. Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia. Ann Emerg Med 1991; 20: 552–4CrossRefGoogle Scholar
  47. 47.
    Kleinman CS, Copel JA, Weinstein EM, et al. Treatment of fetal supraventricular tachyarrhythmias. J Clin Ultrasound 1985; 13: 265–73PubMedCrossRefGoogle Scholar
  48. 48.
    Camm AJ, Garrat CJ. Adenosine and supraventricular tachycardia. N Engl J Med 1991; 325: 1621–9PubMedCrossRefGoogle Scholar
  49. 49.
    Jaqueti J, Martinez-Hernandez D, Hernandez-Garcia R, et al. Adenosine deaminase in pregnant serum. Clin Chem 1990; 36: 2144PubMedGoogle Scholar
  50. 50.
    Mariani PJ. Pharmacotherapy of pregnancy-related SVT [letter]. Ann Emerg Med 1992; 21: 229PubMedCrossRefGoogle Scholar
  51. 51.
    Elkayam U, Goodwin TM. Adenosine therapy for supraventricular tachycardia during pregnancy. Am J Cardiol 1995; 75: 521–3PubMedCrossRefGoogle Scholar
  52. 52.
    Mason BA, Ogjunyemi D, Punla O, et al. Maternal and fetal cardiorespiratory responses to adenosine in sheep. Am J Obstet Gynecol 1993; 168: 1558–61PubMedGoogle Scholar
  53. 53.
    Page RL. Arrhythmias during pregnancy. Cardiac Electrophysiol Rev 1997; 1: 278–82CrossRefGoogle Scholar
  54. 54.
    Chan V, Tse TF, Wong V. Transfer of digoxin across the placenta and into breast milk. Br J Obstet Gynaecol 1978; 85: 605–9PubMedCrossRefGoogle Scholar
  55. 55.
    Rogers MC, Willerson JT, Goldblatt A, et al. Serum digoxin concentrations in the fetus, neonate and infant. N Engl J Med 1972; 287: 1010–3PubMedCrossRefGoogle Scholar
  56. 56.
    Kerenyi TD, Gleicher N, Meller J, et al. Transplacental cardioversion of intrauterine supraventricular tachycardia with digitalis. Lancet 1980; 2: 393–5PubMedCrossRefGoogle Scholar
  57. 57.
    King CR, Mattioli L, Goertz KK, et al. Successful treatment of fetal supraventricular tachycardia with maternal digoxin therapy. Chest 1984; 85: 573–5PubMedCrossRefGoogle Scholar
  58. 58.
    Szekely P, Julian DG. Heart disease and pregnancy. Curr Probl Cardiol 1979; 4: 1–74PubMedCrossRefGoogle Scholar
  59. 59.
    Parilla B, Strasburger JF, Socol ML. Fetal supraventricular tachycardia complicated by hydrops fetalis: a role for direct fetal intramuscular therapy. Am J Perinatol 1996; 13: 483–6PubMedCrossRefGoogle Scholar
  60. 60.
    Mitani GM, Harrison EC, Steingberg I, et al. Digitalis glycosides in pregnancy. In: Elkayam U, Gleicher N, editors. Cardiac problems in pregnancy: diagnosis and management of maternal and fetal disease. New York: Liss, 1990: 417–27Google Scholar
  61. 61.
    Gonzalez AR, Phelps SJ, Cochran EB, et al. Digoxin-like immunoreactive substance in pregnancy. Am J Obstet Gynecol 1987; 157: 660–4PubMedGoogle Scholar
  62. 62.
    Rosemond RL. Cardioversion during pregnancy. JAMA 1993; 269: 3167PubMedCrossRefGoogle Scholar
  63. 63.
    Finlay AY, Edmonds V.D.C. cardioversion in pregnancy. Br J Clin Pract 1979; 33: 88–94PubMedGoogle Scholar
  64. 64.
    Klepper I. Cardioversion in late pregnancy. Anesthesia 1981; 36: 611–6CrossRefGoogle Scholar
  65. 65.
    DeSilva RA, Graboys TB, Podrid PJ, et al. Cardioversion and defibrillation. Am Heart J 1980; 100: 881–95PubMedCrossRefGoogle Scholar
  66. 66.
    Piper JM, Berkus M, Ridgeway LE III. Pregnancy complicated by chronic cardiomyopathy and an automatic implantable cardioverter defibrillator. Am J Obstet Gynecol 1992; 167: 506–7PubMedGoogle Scholar
  67. 67.
    Lee RV, Rodgers BD, White LM, et al. Cardiopulmonary resuscitation of pregnant women. Am J Med 1986; 81: 311–8PubMedCrossRefGoogle Scholar
  68. 68.
    Rees GAD, Willis BA. Resuscitation in pregnancy. In: Evans TR, editor. ABC of resuscitation. 2nd ed. London: BMJ 1990: 50–3Google Scholar
  69. 69.
    Perkins V. CPR during pregnancy [letter]. Am Heart J 1995; 132: 1319CrossRefGoogle Scholar
  70. 70.
    Page RL. CPR during pregnancy [letter]. Am Heart J 1995; 132: 1319CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Division of Cardiology-CS7.102, Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations