ESC Congress 2010 Drug Therapy in Pregnancy: Atrial Fibrillation Deborah Wolbrette, M.D. Professor of Medicine
No Conflicts to Disclose
Pregnancy May be Arrhythmogenic Hormonal Increased estrogen Increased β-human chorionic gonadotropin Hemodynamic Increased circulating volume Cardiac output doubles Myocardial stretch Autonomic High plasma catecholamine concentration Increased adrenergic receptor sensitivity Increased sympathetic tone
Antiarrhythmic Drug Therapy Challenge in pregnancy Possible fetal injury No study data
FDA Pregnancy Risk Classification FDA Class Class A Class B Class C Class D Description controlled studies show no risk no evidence of risk in pregnant women, but either animal studies do show risk, or no adequate human studies have been conducted studies in pregnant women are lacking, and animal studies are positive for fetal risk, or lacking positive evidence of risk can be used if potential benefit outweighs risk Class X contraindicated do not use, regardless of potential benefit
Drug Class Antiarrhythmic Drugs Drug FDA Risk Class Fetal Side Effects IA Quinidine C thrombocytopenia, 8 th nerve toxicity IA Procainamide C none known IA Disopyramide C uterine contractions IB Lidocaine B central nervous system depression at toxic levels IB Mexiletine C little data available IC Flecainide C none known IC Propafenone C none known II Propranolol C intrauterine growth retardation II Metoprolol C intrauterine growth retardation II Atenolol D intrauterine growth retardation, preterm delivery III Sotalol B none known III Amiodarone D congenital malformations, thyroid toxicity III Dronedarone X teratogenic in animals III Ibutilide C no data available III Dofetilide C no data available IV Verapamil C hypotension with IV use IV Diltiazem C little data available Digoxin C monitor for digoxin toxicity Adenosine C none known
General Principles of AAD Use During Pregnancy 1. Documented, hemodynamically significant arrhythmias 2. Benefit outweighs risk for mother and fetus 3. Avoid use in first trimester 4. Lowest effective drug dose 5. Frequent drug monitoring by EKG (& blood level) 6. Use drugs with longest (& safest) track record Kron J, Conti JB. J Interv Card Electrophysiol. 2007;19:95-107.
Atrial Fibrillation & Atrial Flutter in Pregnancy Rare in absence of structural heart disease or endocrine abnormality Evaluate for congenital heart disease, rheumatic heart disease, and hyperthyroid state Fast ventricular response is poorly tolerated with mitral stenosis
Pregnancy & Congenital Heart Disease Incidence of rheumatic heart disease greatly decreased CHD is now most common form of heart disease found in pregnant women in the U.S. Most arrhythmias history of major corrective surgery, involving atria Usually atrial arrhythmias atypical A flutter, A fibrillation, atrial tachycardia Most arrhythmias can be managed with AVN blocking agents
Afib During Pregnancy Objectives Ventricular rate control Early CV (within 48 hours) to avoid anticoagulation Fetal monitoring recommended during and following CV Kron J, Conti JB. J Interv Card Electrophysiol. 2007;19:95-107.
ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation Pregnancy 1. Rate control with digoxin, β blocker or nondihydropyridine calcium channel blocker (diltiazem or verapamil) 2. DC cardioversion if hemodynamically unstable
Rate Control of Afib in Pregnancy Digoxin extensive use in pregnancy β blockers most FDA class C Atenolol (D) Propranolol Metoprolol Avoid due to intrauterine growth retardation Long HX of safe use Frequent use Calcium Channel Blockers - Class C Verapmil First choice in this class IV bolus may cause maternal & fetal distress
Rate Control of Afib in Pregnancy Avoid verapamil and digoxin for preexcited Afib can enhance conduction via the accessory pathway
ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation Pregnancy Class IIb Pharmacological CV (if hemodynamically stable) with quinidine* or procainamide *long HX of safe use in pregnancy
ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation Class IA AAD s are no longer included in the CV algorithms for Afib due to unestablished efficacy and safety concerns Reiffel JA. PACE 2009;32:1073-1084.
Chemical Conversion of Afib/flutter Ibutilide Flecainide Propafenone (DC CV if ineffective) Reiffel, JA. PACE 2009;32:1073-1084.
Class III AAD FDA category C Ibutilide Use During Pregnancy Acute conversion of Afib/flutter of short duration (<7 days) IV 1 mg over 10 min (can repeat) Fetal monitoring Case reports of successful use Burkart TA, et al. PACE 2007;30:283. Kockova R, et al. J Cardiovasc Electrophysiol 2007;18:1.
Advantages Ibutilide Use During No sedation required Pregnancy Efficacy 80% for A flutter Disadvantages 50% for A fib Acute IV use only, due to extensive first-pass metabolism Monitor for TDP until QT returns to normal Prophylactic IV MgSO 4 can reduce TDP risk
Pill-in-Pocket Approach Flecainide (IC) Single oral dose 200 mg patients <70 kg 300 mg patients >70 kg Propafenone (IC) Single oral dose 450 mg patients <70 kg 600 mg patients >70 kg IV flecainide & propafenone not available in U.S. IC agents no SHD or HF Reiffel JA. PACE 2009;32:1073-1084.
Prophylactic Drug Therapy of Afib/flutter Flecainide (no SHD) Sotalol (FDA Class B) ACC/AHA/ESC Guidelines for SVT in Pregnancy No recommendations for Afib/flutter
Prophylactic Drug Therapy of SVT (ACC/AHA/ESC Guidelines 2003) First Line Digoxin or β Blocker (propranolol or metoprolol) Second Line - Sotalol (FDA Class B) Flecainide (no SHD)
ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation Pregnancy Class I Indication Protection against thromboembolism is recommended throughout pregnancy for all patients with Afib (except those with lone Afib or low thromboembolic risk) Class II b (Afib & risk factors) 1. Heparin during first trimester and last month (continuous IV or subcutaneous every 12 hrs.) 2. LMWH subcutaneous during first trimester and last month 3. Oral anticoagulant during second trimester
ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation Congenital or valvular heart disease high risk of thromboembolism Warfarin Crosses placental barrier Teratogenic in first trimester Fetal hemorrhage in late pregnancy FDA category X Heparin Does not cross placenta Preferred anticoagulant FDA category C
Final Thoughts 1. Acute treatment of arrhythmias during pregnancy is similar to that for general population 2. Chronic therapy during pregnancy reserved for frequent, hemodynamically significant episodes
Challenge for the Future Limited data on drug therapy during pregnancy (mainly case reports) Newer drugs may be safer and more effective than older ones with a long track record Need Registry of AAD use during pregnancy