Management of Arrhythmias in Pregnancy




During pregnancy, preexisting arrhythmias may or may not increase. Hemodynamic changes, particularly during the third trimester, may predispose to some arrhythmias. Palpitations due to higher plasma volumes or ectopy are common and benign; noninvasive ambulatory monitoring may be considered if symptoms suggest sustained or symptomatic tachyarrhythmias. Compression of abdominal venous or arterial vessels can cause supine hypotension, associated symptoms, and exacerbation of neurocardiogenic syncope. Management includes nonpharmacologic measures, such as maintaining good hydration, support stockings, avoidance of supine positioning, and possibly higher salt intake. Some forms of long QT syndrome (LQTS), especially LQTS 2, are associated with higher risk for ventricular arrhythmias during pregnancy or in the postpartum period. β-blocker therapy can often be continued. For those individuals who develop a cardiomyopathy or who are at risk for life-threatening ventricular arrhythmias, a wearable cardioverter defibrillator may be considered.


Antiarrhythmic and anticoagulant medications during pregnancy


Risks of antiarrhythmic medications to the mother and fetus should be considered. Medications may affect the fetus if they cross the placenta. Fetal arrhythmias can potentially be treated by medications that cross the placenta. Dosing may be complicated by the higher volume status, increase in renal and hepatic blood flow, lower plasma protein concentration, and hormonal changes that can affect drug levels and efficacy. Safety of drugs to the child during breast feeding should also be considered.


Table 13.1 summarizes U.S. Food and Drug Administration (FDA) pregnancy categories for common antiarrhythmic and anticoagulant medications. However, classification is not provided for drugs approved after June 30, 2015, when the FDA removed common antiarrhythmic and anticoagulant medications from the Physician Labeling Rule format, requiring information to assist in counseling for pregnancy, lactation, and females and males of reproductive potential.



Table 13.1

U.S. Food and drug administration pregnancy categories





















A No risk in controlled human studies: Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
B No risk in other studies: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women or animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.
C Risk not ruled out: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may outweigh potential risks.
D Positive evidence of risk: Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may outweigh potential risks.
X Contraindicated in pregnancy: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. Risks in pregnant women clearly outweigh potential benefits.
N The FDA has not classified the drug.

FDA, U.S. Food and Drug Administration.


Table 13.2 summarizes pregnancy categories for commonly used drugs in arrhythmia management. Few drugs are in category B, where there is no evidence of harm in humans and risk to the fetus is assessed to be rare, but these drugs include lidocaine, pindolol, and sotalol. The most common category is C, for which there is a lack of adequate studies. Older drugs, with which there is more experience, may be preferable to newer drugs, with which there is less experience. Drugs that should be avoided include those in category D, for which there is evidence of risk, and category X, which includes contraindicated drugs. These drugs to be avoided include phenytoin (fetal hydantoin syndrome and bleeding risk), amiodarone (fetal thyroid abnormality), dronedarone (teratogenicity), warfarin (see below), and atenolol (evidence of fetal risk). Risks and benefits of drug therapy before, during, and after pregnancy should be discussed in detail with patients.



Table 13.2

Common drugs used to treat arrhythmias and their safety in pregnancy and lactation


























































































































































































































































































Class Drug FDA Category Crosses Placenta Pregnancy Comments Crosses to Breast Milk Breast-feeding Comments
Class IA
Quinidine C Yes Relatively low risk for fetus; neonatal thrombocytopenia reported. Has been used to treat fetal arrhythmias. Yes Limited data in humans. Probably low risk.
Procainamide C Yes Limited data in humans. Has been used to treat fetal arrhythmias. Yes Limited data in humans. Probably low risk.
Disopyramide C Yes Risk in third trimester. Oxytocic effect: may cause contractions; adverse effects at high doses in animals. Yes Limited data in humans. Probably low risk.
Class IB
Mexiletine C Probably Limited data in humans. Low risk suggested by animal studies. Yes Limited data in humans. Probably low risk.
Lidocaine B Yes Human experience suggests low risk. Yes Limited data in humans. Probably low risk.
Phenytoin D Yes Avoid use for arrhythmias.
Congenital abnormalities, fetal hydantoin syndrome, malignancies, hemorrhage in the newborn.
Yes Expected to be low risk.
Class IC
Flecainide C Yes Limited data in humans. Animal studies suggest risk at higher doses. Used to treat fetal arrhythmias. Yes Limited data in humans. Probably low risk.
Propafenone C Yes Limited human data; animal data suggest risk at higher doses. Until more information, generally reserve use for when other agents are not effective. Yes Limited data in humans. Probably low risk.
Propranolol C Yes Risk in second/third trimester. Yes Limited data in humans. Possible clinically significant risk. Breast feeding not recommended.
Atenolol D Yes Risk in second/third trimester. Yes Limited data in humans. Possible clinically significant risk. Breast feeding not recommended. With availability of other agents, avoid renally excreted β-blockers, such as atenolol.
Metoprolol C Yes Risk in second/third trimester. Only limited experience in first trimester. Yes Limited data in humans. Possible clinically significant risk. Breast feeding not recommended.
Carvedilol C Yes Risk in second/third trimester. Unknown/probably No data in humans. Might be low risk.
Pindolol B Yes Risk in second/third trimester. Yes No data in humans. Possible clinically significant risk. Breast feeding not recommended.
Acebutolol B Yes Limited data in humans. Low risk suggested by animal studies. Yes Limited data in humans. Possible clinically significant risk. Breast feeding not recommended.
Bisoprolol C Probably Risk in second/third trimester. Unknown/probably No data in humans. Possible clinically significant risk. Breast feeding not recommended.
Class III
Ibutilide C Unknown/Possibly Limited data in humans. Animal studies suggest risk at higher doses. Unknown No data in humans. Might be low risk. Probably can be used.
Amiodarone D Yes Significant risk suggested by human and animal studies. Should avoid, if possible. Yes Contraindicated.
Sotalol B Yes Risk in second/third trimester. Yes Limited data in humans. Possible clinically significant risk. Breast feeding not recommended.
Dofetilide C Unknown/probably No data in humans. Animal studies suggest risk at higher doses with possible teratogenicity and toxicity. Unknown/probably No data in humans. Possible clinically significant risk. Breast feeding not recommended.
Dronedarone X Unknown/probably No data in humans. Animal studies suggest risk at higher doses. Contraindicated, especially in first trimester, no data later in pregnancy; fetal abnormalities in animals. Unknown/probably No data in humans. Possible clinically significant risk. Breast feeding not recommended.
Class IV: Calcium Channel Blockers
Diltiazem C Yes Limited experience, but low risk suggested. Yes Limited data in humans suggest low risk. Probably can be used.
Verapamil C Yes Human experience suggests very low risk. Can be used. Yes Limited data in humans suggest low risk. Probably can be used.
Miscellaneous
Adenosine C Unknown Human experience suggests very low risk. Can be used when maternal benefit greatly exceeds embryo-fetal risk. Unknown No data in humans. Might be low risk. Probably can be used.
Digoxin C Yes Human experience suggests very low risk. Can be used. Yes Not expected to cause significant infant toxicity. Can be used.
Ivabradine N Unknown Fetal toxicity and teratogenesis in animals. Unknown/Probably Not recommended.
Fludrocortisone C Unknown Adverse events observed with corticosteroids in animal studies. Yes
Midodrine C Unknown/probably Limited information; adverse events in animal studies. Unknown/probably
Anticoagulants
Warfarin D (mechanical heart valves)
X (other indications)
Yes Contraindicated in first trimester. Teratogenic with coumarin embryopathy in first trimester; CNS abnormalities in any trimester; spontaneous abortion, fetal hemorrhage, fetal death.
Contraindicated in pregnancy except with mechanical heart valves at high risk for thromboembolism.
No Expected to be low risk for infant. May be used in breast-feeding women.
Apixaban B Yes in animals No data in humans. Low risk suggested by animal studies.
Avoid use in pregnancy; data insufficient.
Unknown/probably No data in humans. Possible clinically significant risk. Breast feeding not recommended; use of alternative anticoagulation preferred.
Dabigatran C Yes No data in humans. Animal studies suggest risk at higher doses. Avoid use in pregnancy. Unknown No data in humans. Possible clinically significant risk. Breast feeding not recommended; use of alternative anticoagulation preferred. Canadian labeling contraindicates.
Edoxaban C Unknown Avoid use in pregnancy. Unknown/Probably Use of alternative anticoagulation recommended.
Rivaroxaban C Yes No data in humans. Animal studies suggest risk at higher doses. Avoid use in pregnancy. Unknown No data in humans. Possible clinically significant risk. Breast feeding not recommended; use of alternative anticoagulation preferred. Canadian labeling contraindicates.

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Jan 30, 2019 | Posted by in CARDIOLOGY | Comments Off on Management of Arrhythmias in Pregnancy

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