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1 I have nothing to disclose.

2 Antiarrhythmic Therapy in Pregnancy Prof. Ali Oto,MD,FESC,FACC,FHRS Department of Cardiology Hacettepe University,Faculty of Medicine Ankara

3 Arrhythmias in pregnancy An increased incidence of maternal cardiac arrhythmias is observed during pregnancy Both premature beats and sustained tachyarrhythmias become more frequent and may even for the first time during pregnancy Symptomatic exacerbation of PSVT occurs in % 0f cases Although most palpitations are benign a new onset VT should be investigated for the underlying structural heart disease carefully Arch Gynecol Obstet 2004;269: Heart 2007;93: Current Opinion in Cardiology 2001;16:40-45

4 ARRHYTHMIAS INCIDENCE IN PREGNANCY IS INCREASING Increasing age of pregnancy and consequent higher frequency of co-morbitidities. Treatment success : Paradoxically,successful Tx of heart diseases in infants and children has resulted in an increase in the prevalence of heart disease in women capable of having a successful pregnancy. Arrhythmias are more common in women with heart disease. (4.5 % vs 1 % ) Clin Cardiol 2012;30: Current Opinion in Cardiology 2001;16:40-45

5 Clin Cardiol 2008;31:538-41

6 Physiological changes during pregnancy Cardiac output 30 to 50% Blood volume 40 to 50% Reduced systemic resistance Increased atrial stretch and end-diastolic volume Serum protein concentration Alteration in gastric secretion and motility Catecholamine level and adrenergic receptor sensitivity Changes in hormonal stimulation of liver enzymes Mild hypokalemia of pregnancy These changes can affect the absorption, bioavailability, and elimination of most drugs! Current Opinion in Cardiology 2001;16:40-45 Arch Gynecol Obstet 2004;269;244-53

7 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

8 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment The diagnostic criteria for arrhythmias are not changed by pregnancy Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

9 Electrocardiographic changes in pregnancy Resting heart rate ~10 beats /min PR, QRS QT intervals The electrical axis shift can more commonly leftward Enlargement of the uterus Q wave and T wave inversion in inf leads Heart 2007;93:

10 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

11 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Treat hemodynamically significant rhythms early Mother s perfusion is compromised Uterine vasoconstriction to allow maternal vital organ perfusion Increased cathecholamine levels and volume shifts ; further compromise uterine blood flow Hemodynamic compromise needs more urgent action in a pregnant women! Clin Cardiol 2012;30:425-34

12 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

13 Worsening factors should be detected Tobacco, caffeine and illicit drug use Behavior modification is needed Electrolytic imbalance, anemia and hyperthyroidism should be evaluated Arch Gynecol Obstet 2004; 269:

14 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

15 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Avoid drugs if possible All antiarrhythmic medications have potential side effects Use drugs if necessary for maternal or fetal safety Remember all drugs used to treat arrhythmias cross the placenta and results in fetal exposure The majority of antiarrhythmic drugs are FDA category C The most worrisome side effect is proarrhythmia Occur with almost all of the Vaughan Williams Class I and III The patient should be monitored regularly Clinical response /Side effect/serum drug levels (when available) Arch Gynecol Obstet 2004;269:244-53

16 FDA Drug Categories Pregnancy category A B C D X Definition of FDA pregnancy categories Definition Controlled studies show no risk. Adequate, well-controlled studies in pregnant women have failed to demonstrate risk to the fetus in any trimester of pregnancy No evidence of risk in humans. Adequate, well-controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility Risk cannot be ruled out. Adequate, well-controlled human studies are lacking, and animal studies have shown a risk to the fetus or are lacking as well. There is chance of fetal harm if the drug administered during pregnancy, but the potential benefits outweigh the risk Positive evidence of risk. Investigational or post-marketing data show risk to the fetus. Nevertheless, potential benefits of the drug may be acceptable when they outweigh the potential risk Contraindicated in pregnancy. Studies in animals or humans have shown fetal risk, which clearly outweighs any possible future benefit to the patient Current Opinion in Cardiology 2001;16:40-45

17 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

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19 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

20 KEY POINTS OF ARRHYTHMIA MANAGEMENT DURING PREGNANCY Document the rhythm before treatment Treat hemodynamically significant rhythms early Evaluate for potential reversible causes Avoid drugs if possible Avoid procedures requiring an X Ray until after the pregnancy Evaluate cardiac anatomy in those with sustained arrhythmias Consult with gynecologist and/or neonatalogist if needed Clin Cardiol 2012;30:425-34

21 ANTIARRHYTHMIC THERAPY IN PREGNANCY TREATMENT OPTIONS Elimination of offending causes Antiarrhythmic drugs Antithrombotic drugs Ablation procedures Implantable devices

22 Frequency,symptoms,duration and tolerability of the arrhythmia Benefit of arrhythmia reduction and termination Maternal and fetal side effects Smallest recommended dose should be used initially If possible therapy should be avoided during the first trimester European Heart Journal 2011;32:

23 Drugs Classification (Vaughan Williams for AA drugs) FDA category Placenta permeable Transfer to breast milk (fetal dose) Adverse effects Adenosine Antiarrhythmic C No No No fetal adverse effects reported (limited human data) Amiodarone Class III D Yes Yes Thyroid insufficiency (9%), hyperthyroidism, goitre, bradycardia, growth retardation, premature birth Atenolol Class II D Yes Yes Hypospadias (first trimester); birth defects, low birth weight, bradycardia and hypoglycemia in fetus Digoxin Cardiac glycoside C Yes Yes Serum levels unreliable, safe Diltiazem Class IV C No Yes Possible teratogenic effects. European Heart J 2011;32: Heart 2007;93:: Current Opinion in Cardiol 2001;16:40-

24 Drugs Classification (Vaughan Williams for AA drugs) FDA category Placenta permeable Transfer to breast milk (fetal dose) Adverse effects Disopyramide Class IA C Yes Yes Uterus contraction Flecainide Class IC C Yes Yes Unknown (limited experience) Lidocaine Class IB B Yes Yes Fetal bradycardia, acidosis, central nervous system toxicity Metoprolol Class II C Yes Yes Bradycardia and hypoglycemia in fetus Mexiletine Class IB C Yes Yes Fetal bradycardia Procainamide Class IA C Yes Yes Unknown (limited experience) Propafenone Class IC C Yes Unknown Unknown (limited experience) Propranolol Class II C Yes Yes Bradycardia and hypoglycemia in fetus European Heart J 2011;32: Heart 2007;93:: Current Opinion in Cardiol 2001;16:40-45

25 Drugs Classification (Vaughan Williams for AA drugs) FDA category Placenta permeable Transfer to breast milk (fetal dose) Adverse effects Quinidine Class IA C Yes Yes Thrombopenia, premature birth, VIII th nerve toxicity. Sotalol Class III B Yes Yes Bradycardia and hypoglycemia in fetus (limited experience) Verapamil oral Class IV C Yes Yes Well tolerated (limited experience during pregnancy) Verapamil i.v. Class IV C Yes Yes Intravenously use is may be associated with a greater risk of hypotension and subsequent fetal hypoperfusion Vernakalant Class III - Unknown Unknown No experience of use in pregnancy. European Heart J 2011;32: Heart 2007;93:: Current Opinion in Cardiol 2001;16:40-45

26 Antiarrhythmic Therapy in Pregnancy Pregnancy with structurally normal heart and minimally symptomatic arrhythmias No treatment other than reassurance is necessary Drug therapy should be reserved for patients with severe symptoms or hemodynamic compromise Clin Cardiol 2012;30:425-34

27 Antiarrhythmic Therapy in Pregnancy Sinus tachycardia The most common tachycardia and tachycardia related cause of hosp admission HR increases gradually during the pregnancy,rarely >100/min >100/min, make sure ECG is sinus tachycardia (Hyperthyroidism,POTS,inapp sin tachycardia) Unless associated with unacceptable symptoms no Tx is needed. If symptoms are significant occasionally BB is indicated Clin Cardiol 2012;30:

28 Antiarrhythmic Therapy in Pregnancy Supraventricular and ventricular ectopic beats Usually no clinical significance Caffeine, smoking and alcohol should be eliminated Drug therapy is not needed in the vast majority of cases If necessary(untolerable Sx), β-blockers may be used (Propranolol, Metoprolol) Clin Cardiol 2012;30:

29 Antiarrhythmic Therapy in Pregnancy Hemodynamically unstable pregnant women Electrical cardioversion J is usually sufficient for SVT J for atrial fibrillation and J for atrial flutter DC cardioversion is safe during all phases of pregnancy Neth Heart J (2011) 19:

30 Challenging arrhythmias in pregnancy 1. Ventricular tachycardia (without structural heart disease) Physical and psychological stresses are the stimuli Usually monomorphic left ventricular type Low risk for subsequent mortality and morbidity Good response to beta blocker therapy 2. Ventricular tachycardia (underlying acquired or congenital structural heart disease) More serious prognosis Hypertrophic cardiomyopathy, right ventricular dysplasia, peripartum cardiomyopathy and coronary artery disease 3. Paroxysmal supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome Current Opinion in Cardiology 2001;16:40-45

31 Antiarrhythmic Therapy in Pregnancy Stable patients with supraventricular tachycardia Vagal maneuvers should be tried first Carotid sinus massage, Valsalva maneuver I.V. adenosine is the first-choice drug when the vagal maneuvers fail (6-12 mg ) Safe but only one report of fetal bradycardia Digoxin, beta-blockers, or calcium channel blockers could also be use d Although these drugs do cross placenta they do not appear to cause substantial harm to fetus In AVRT with an accessory pathway, class I antiarrhythmic drugs (procainamide and quinidine) may be used for blocking accessory pathway conduction International Journal of Cardiology 2003;88: Clin Cardiol 2012;30; Arch Gynecol Obstet 2004; 269:

32 Summary recommendations by ESC Guidelines

33 Antiarrhythmic Therapy in Pregnancy Atrial flutter and atrial fibrillation Usually associated with structural heart disease (congenital or valvular) and thyrotoxicosis Early cardioversion should be performed to avoid the need of anticoagulation Quinidine, Procainamide I.V. Ibutilide, flecainide, propafenone, or vernacalant There is even less or no experience These drugs may only be considered if all other attempts at cardioversion fail Rate control When cardioversion is not successful Ideally <90 bpm at rest and <140 bpm with exercise β-blockers (propranolol, metoprolol), digoxin or verapamil Clin Cardiol 2012;30: Heart 2007;93:

34 Antiarrhythmic Therapy in Pregnancy Ventricular tachycardia (Stable patients) Initial therapy Lidocaine or procainamide If refractory to electrical cardioversion or not responding to other drugs i.v. Amiodarone may be be considered Prophylactic therapy Cardioselective beta-blockers (first choice) Sotalol (if beta-blockers is ineffective) Catheter ablation may be considered in the case of drug-refractory and poorly tolerated tachycardias Idiopathic right ventricular outflow tract tachycardia Most frequent type Verapamil, B-blocking agent Clin Cardiol 2012;30: Heart 2007;93:

35 Antiarrhythmic Therapy in Pregnancy Long QT syndrome QT intervals during pregnancy Protective effect in pregnant women with long QT syndrome As heart rate decreases after delivery, increase the incidence of torsade de pointes in the postpartum period Beta-blockers has been shown to decrease the risk of torsade de pointes related cardiac events (death, aborted cardiac arrest, or syncope) Beta-blocker therapy must be continued during pregnancy and especially the postpartum period Implantable cardioverter-defibrillator (ICD) Patients with aborted sudden death ICD does not cause complications or adverse events Heart 2007;93:

36 Summary recommendations by ESC Guidelines

37 FINAL THOUGHTS Arrhythmias are common during pregnancy and the incidence is increasing Treatment of hemodynamically significant arrhythmias with more urgency is essential.if drug fails DC cardioversion can be used safely. Drugs to be avoided if possible:consider maternal safety and risks to the fetus when choosing the treatment;drugs with the longest record of safety should be used first. Radiation procedures should be deferred to after delivery if possible.