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.
| 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. |
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.
| 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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