Supraventricular arrhythmias during pregnancy

INTRODUCTION — Arrhythmias are the most common cardiac complication encountered during pregnancy in females with and without structural heart disease [1-3]. In the United States, the incidence of pregnancy-related hospitalizations with arrhythmias has increased between 2000 and 2012 primarily due to increases in the incidence of atrial fibrillation and ventricular tachycardia [4].

Arrhythmias may manifest for the first time during pregnancy, and in other cases, pregnancy can trigger exacerbations in those with pre-existing arrhythmias [1,5,6]. Females with established arrhythmias or structural heart disease are at highest risk of developing arrhythmias during pregnancy. In addition, there has been an increase in the number of female patients of childbearing age with congenital heart disease due to surgical advances and improvements in the care of adults with congenital heart disease, and these are at particularly high risk for arrhythmias (figure 1) [1,2,7-11]. Because of these associations, any pregnant person who presents with an arrhythmia should have a clinical evaluation with a complete history and cardiac examination, an electrocardiogram, and a transthoracic echocardiogram to evaluate for evidence of structural heart disease.

In general, the approach to the treatment of arrhythmias in pregnancy is similar to that in the nonpregnant patient. However, due to the theoretical or known adverse effects of antiarrhythmic drugs on the fetus, antiarrhythmic drugs are often reserved for the treatment of arrhythmias associated with clinically significant symptoms or hemodynamic compromise [12-14]. Treatment recommendations are hampered by the lack of randomized trials and very little or no data on efficacy or safety of antiarrhythmic drugs during pregnancy. Choice of therapy, for the most part, is based on limited data from animal studies, case reports, and observational studies, as well as clinical experience.

The prevalence, clinical presentation, and management of supraventricular arrhythmias during pregnancy will be reviewed. Electrocardiographic characteristics of supraventricular arrhythmias, as well as issues relating to conduction disorders, ventricular arrhythmias, and cardiac arrest during pregnancy, are discussed separately. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias" and "Maternal conduction disorders and bradycardia during pregnancy" and "Ventricular arrhythmias during pregnancy".)

MECHANISM OF ARRHYTHMOGENESIS IN PREGNANCY — The exact mechanism of increased arrhythmia burden during pregnancy is unclear, but has been attributed to hemodynamic, hormonal, and autonomic changes related to pregnancy.

The hemodynamic changes of pregnancy have been well studied, and a number of these changes likely contributes to the development of arrhythmias during pregnancy [15-17]. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)

Intravascular volume increases, augmenting the preload on the ventricles and increasing both atrial and ventricular size [15,18-21]. Atrial and ventricular myocardial stretch may contribute to arrhythmogenesis, due to stretch-activated ion channel activity causing membrane depolarization, shortened refractoriness, slowed conduction, and spatial dispersion of refractoriness and conduction [22-25]. There is also an increase in resting heart rate, which has been associated with markers of arrhythmogenesis such as late potentials, premature ventricular contractions, and depressed heart rate variability [26].

Few studies have been published on the influence of hormonal and autonomic changes on arrhythmogenesis in pregnancy. Although catecholamine levels do not appear to change during pregnancy, there is an increase in adrenergic responsiveness during pregnancy [27-31]. This increased adrenergic activity during pregnancy may also contribute to enhanced automaticity and triggered activity [32].

SYMPTOM-RHYTHM CORRELATION — Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. The differential diagnosis of palpitations is extensive and the diagnostic evaluation of pregnant individuals with palpitations does not differ from nonpregnant individuals. (See "Evaluation of palpitations in adults".)

One study compared 110 pregnant females with symptoms suggestive of possible arrhythmia (palpitations: 87 percent; dizziness: 13 percent; syncope/presyncope: 6 percent) with 52 pregnant females evaluated for a functional murmur [33]. Prevalence of supraventricular and ventricular ectopic activity on 24-hour Holter ambulatory monitoring was similar in the symptomatic and control groups.

Only 10 percent of symptomatic episodes were accompanied by the presence of arrhythmias. A sensation of palpitations during pregnancy, in the absence of concomitant cardiac arrhythmias, may be related to the high output state, including increased heart rate, decreased peripheral resistance, and increased stroke volumes. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)

In another study of 96 patients with symptoms, event loop recorders confirmed benign arrhythmias in the majority of patients. The longer monitoring allowed for better detection of more complex arrhythmias [34].

ATRIAL PREMATURE BEATS — Premature atrial complexes (PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) are very frequent in pregnant patients and the prevalence is dependent on the duration of observation. (See "Supraventricular premature beats".)

In one study of 162 pregnancies in patients with structurally normal hearts evaluated with 24-hour Holter monitoring, the prevalence of PACs was 57 percent and frequent PACs (>100 PACs per 24 hours) occurred in six percent of pregnancies [33]. There was a significant reduction in the frequency of atrial and ventricular ectopic activity in nine patients in whom Holter monitoring was repeated postpartum.

Clinical presentation — PACs produce few or no symptoms in the majority of pregnant patients, although some people may have symptoms of palpitations.

Management — No therapy is required for PACs in the asymptomatic woman. Pregnant persons with symptomatic PACs should be reassured of the benign nature of PACs and be advised to discontinue potential precipitant factors such as smoking, coffee intake, alcohol intake, or other stimulants.

If ectopic activity continues and is associated with intolerable symptoms, treatment with cardioselective beta blockers such as metoprolol can be effective. (See 'Issues regarding antiarrhythmic drug treatment' below.)

PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA — Paroxysmal supraventricular tachycardia (PSVT) describes a tachycardia that is caused, in the vast majority of patients, either by reentry within the atrioventricular (AV) node or by use of an accessory pathway, either manifest or concealed. (See "Atrioventricular nodal reentrant tachycardia".)

In pregnant patients with structurally normal hearts, AV nodal reentrant tachycardia (AVNRT) is the most common PSVT, followed by AV reciprocating tachycardia (AVRT) [5]. The prevalence of PSVT has been estimated at 22 to 24 per 100,000 hospital admissions in pregnant patients [4,35]. A population-based cohort study of pregnancies in Taiwan between 2001 and 2012 demonstrated that PSVT in pregnant patients was associated with severe maternal morbidity, cesarean deliveries, low birth weight babies, preterm labor, and obvious fetal abnormalities in comparison with females without PSVT [36]. These data should be interpreted with caution, however, as there are a number of possible explanations for this association: while PSVT in pregnancy may be directly detrimental to the developing fetus, PSVT may also be associated with other maternal factors that impact maternal and fetal health, and patients presenting with PSVT may have had more intensive fetal monitoring as a consequence of their presentation with PSVT, with possible earlier delivery and lower birth weight.

There are discrepancies between studies as to whether pregnancy increases the risk of first onset of PSVT [5,37]. One study of 38 patients with PSVT and a previous pregnancy found that the initial onset of PSVT occurred during pregnancy in 13 patients (34 percent). The estimated relative risk of first onset of PSVT during pregnancy was 5.1 (95 percent confidence interval 2.8 to 9.2) [37]. In contrast, another study of 173 patients with symptomatic PSVT and a history of pregnancy referred for electrophysiologic testing and radiofrequency catheter ablation, reported that only 4.6 percent had initial onset of PSVT during pregnancy [5]. In that series, pregnancy was not associated with first onset of PSVT. Furthermore, in patients with AVNRT there was a decreased risk of first onset of AVNRT during pregnancy (relative risk 0.11, 95% CI 0.02-0.56).

The same study found that among patients with a first onset of PSVT before pregnancy, the majority (85 percent) of patients had an exacerbation of PSVT during pregnancy [5]. Exacerbations of PSVT during pregnancy were more symptomatic (assessed by a semiquantitative questionnaire) when compared with arrhythmias during nonpregnant periods.

Clinical presentation — The presentation of PSVT during pregnancy is the same as in the nonpregnant state and includes symptoms of palpitations that may be associated with presyncope, syncope, dyspnea, and/or chest pain. Patients with PSVT typically describe a regular and rapid tachycardia of abrupt onset, with or without abrupt termination. The clinical and hemodynamic consequences of the arrhythmia depend on many variables including the presence or absence of structural heart disease. For example, in women with Ebstein’s anomaly of the tricuspid valve, symptomatic AVRT episodes can result in serious hemodynamic deterioration [13,38]. PSVT is usually well tolerated in pregnant patients without structural heart disease [39-43].

Management — Our management approach is in general agreement with the recommendations for pregnant patients made by professional society guidelines for the management of patients with supraventricular tachycardia [11,13,44].

Management of acute episodes — If hemodynamic compromise is evident, direct-current cardioversion should be performed [11,44]. (See "Cardioversion for specific arrhythmias" and "Basic principles and technique of external electrical cardioversion and defibrillation" and "Cardioversion for specific arrhythmias", section on 'Cardioversion during pregnancy'.)

When the patient is hemodynamically stable, acute episodes of PSVT may be terminated by transiently blocking AV nodal conduction [11]. If vagal maneuvers (eg, Valsalva maneuver or carotid sinus massage) fail, intravenous adenosine (6 to 18 mg) is an appropriate choice in pregnancy, terminating approximately 90 percent of PSVT [45]. Case reports have demonstrated the effectiveness of adenosine in pregnant patients, although in most of the reports adenosine was administrated in the second and third trimester [46]. (See "Atrioventricular nodal reentrant tachycardia", section on 'Initial management'.)

Adenosine has a very short half-life (<10 seconds), reducing the placental exposure to adenosine. Despite reduced adenosine deaminase activity during pregnancy (25 percent) [47], the adenosine dose required for PSVT termination during pregnancy is not reduced, possibly due to the increased volume of distribution [48]. (See 'Issues regarding antiarrhythmic drug treatment' below.)

Recommended second-line drugs are intravenous beta-1 selective blockers [11,44,46]. The experience with intravenous verapamil is limited [49], and the longer half-life (5.3 hours) of verapamil can cause significant hypotension, especially when given as a rapid intravenous bolus injection [48]. (See 'Issues regarding antiarrhythmic drug treatment' below.)

Prophylactic pharmacologic therapy — Prevention of PSVT in patients without WPW syndrome can be accomplished with a number of AV nodal blocking agents (ie, beta-1 selective blockers [except atenolol] or verapamil, in order of preference) [11,13,48,50,51]. In pregnant patients without structural heart disease who have PSVT not controlled with AV nodal blocking agents, flecainide, propafenone, or sotalol can be considered for the prevention of PSVT [11,13,50]. In pregnant patients with WPW syndrome and without ischemic or structural heart disease, flecainide or propafenone are options for the prevention of PSVT [11,13]. (See 'Issues regarding antiarrhythmic drug treatment' below and "Atrioventricular nodal reentrant tachycardia", section on 'Preventive therapy'.)

Experience with digoxin is extensive and it is considered safe during pregnancy [52]. However, the efficacy of digoxin for prophylaxis has not been demonstrated. One small, randomized, cross-over study of 11 nonpregnant patients showed that there was similar efficacy between digoxin, propranolol, and verapamil with respect to the frequency or duration of PSVT [53]. Propranolol and metoprolol are often used, but the potential fetal risks of beta blockers need to be discussed with the mother, in particular the risk of intra-uterine growth restriction [51] (see 'Issues regarding antiarrhythmic drug treatment' below). Atenolol should not be used for treatment of arrhythmias if alternative medications are available.

Because pregnancy may exacerbate PSVT, radiofrequency catheter ablation is recommended in symptomatic patients with recurrent PSVT who plan to become pregnant [11]. In patients with malignant, drug-resistant arrhythmias, radiofrequency catheter ablation during pregnancy may be an option in selected cases [11,13,54]. (See 'Radiofrequency catheter ablation' below and "Atrioventricular nodal reentrant tachycardia".)

In general, anticoagulation therapy is not indicated for SVT such as AVNRT, AVRT over a bypass tract, or ectopic atrial tachycardia.

FOCAL ATRIAL TACHYCARDIA — Focal atrial tachycardia is relatively rare during pregnancy. (See "Focal atrial tachycardia".)

Although this arrhythmia is often associated with structural heart disease in nonpregnant patients, most reports of atrial tachycardia during pregnancy have been reported in patients without apparent structural heart disease [42,43].

Clinical presentation — As in the nonpregnant state, this arrhythmia is often persistent and can be refractory to treatment, including direct current (DC) cardioversion [42,43]. Because many atrial tachycardias are caused by enhanced automaticity, vagal maneuvers or the use of antiarrhythmic agents that decrease atrioventricular nodal conduction (eg, adenosine, digoxin, beta blockers, calcium channel blockers), will usually not terminate the arrhythmia [42,43].

In most reported cases, the arrhythmia subsides and terminates shortly after delivery, suggesting that pregnancy may contribute to the initiation and maintenance of this tachyarrhythmia [42,43].

Diagnosis and management — The differentiation between atrial tachycardia and other supraventricular tachyarrhythmias may be difficult. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".)

The administration of adenosine may be useful as a therapeutic and diagnostic tool. Because atrial tachycardia is difficult to treat and is generally well tolerated by the mother and the fetus, urgent DC cardioversion or administration of multiple intravenous drugs is not recommended when pregnant patients are hemodynamically stable.

The goal of therapy should be to achieve adequate rate control. The risk of not treating an incessant atrial tachycardia is the development of a tachycardia-induced cardiomyopathy [55]. (See "Arrhythmia-induced cardiomyopathy".)

Rate control can be achieved with beta blockers, digoxin, or verapamil [11,42-44,50], with reservation of sotalol, flecainide, or propafenone (table 1) [43,48,56]. Decisions regarding the use of other antiarrhythmic drugs or consideration of ablation should be made with the assistance of an electrophysiologist.

For patients with hemodynamically significant atrial tachycardia with a rapid ventricular response who do not respond to medical therapy and do not have a reversible precipitating cause, DC cardioversion may be required. However, as noted above, atrial tachycardias may be particularly resistant to cardioversion. (See "Cardioversion for specific arrhythmias", section on 'Cardioversion during pregnancy' and 'Electrical cardioversion' below.)

In some pregnant patients with incessant atrial tachycardia, radiofrequency catheter ablation may need to be considered [11,13,54,57]. (See 'Radiofrequency catheter ablation' below and "Focal atrial tachycardia".)

ATRIAL FIBRILLATION AND FLUTTER — The management of atrial fibrillation is often similar in pregnancy compared with the non-pregnant state. Unique considerations include:

●Choice of specific pharmacotherapy to maximize safety and minimize adverse effects during pregnancy and lactation.

●Hemodynamic changes across pregnancy and labor and delivery, particularly in pregnant patients with structural heart disease.

●Recognition of pregnancy as a hypercoagulable, prothrombotic state.

●Early and frequent labor and delivery planning throughout pregnancy. This includes shared decision-making between the patient and multidisciplinary care team.

Epidemiology and risk factors — Atrial fibrillation and flutter during pregnancy are relatively uncommon. In an Agency for Healthcare Research Quality database of >1200 hospitals across the United States, the prevalence of atrial fibrillation was 27 per 100,000 pregnancy-related hospital admissions, and atrial flutter was 4 per 100,000 [4]. This study found that atrial fibrillation rates nearly doubled from 2000 to 2012 (18 to 35 per 100,000 hospital admissions). Advancing maternal age and higher burden of AF risk factors (hypertension, diabetes mellitus, obesity, and congenital heart disease) over this time period likely explain increased atrial fibrillation rates.

Although atrial fibrillation and flutter can occur in pregnant patients with structurally normal hearts [58,59], they are more common in pregnant patients with structural heart disease, such as rheumatic heart disease, valvular heart disease, hypertrophic cardiomyopathy [60], peripartum cardiomyopathy, and congenital heart disease [6,61-63]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Overview of atrial flutter".)

Metabolic disturbances such as hyperthyroidism, electrolyte imbalances, and alcohol use can also contribute to the development of atrial fibrillation during pregnancy.

Clinical presentation — The clinical presentation and hemodynamic consequences of atrial fibrillation and flutter depend on many variables, including the underlying heart condition and the associated ventricular response rate. In addition to hemodynamic consequences, pregnant patients with atrial fibrillation are at increased risk of systemic embolism both from hemostatic changes seen in normal pregnancy [64] and from atrial fibrillation. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)

Common presenting symptoms of atrial fibrillation in pregnancy are palpitations, feeling of rapid heart beating, heart fluttering, lightheadedness, syncope, or dyspnea.

Atrial fibrillation is less well tolerated in persons with preexisting structural heart disease. Symptoms may be further exacerbated by pregnancy-related physiologic changes, such as increased blood volume, increased heart rate, shunting of blood to the uteroplacental system, and anemia. Symptoms include concomitant pulmonary edema, dyspnea at rest and on exertion, dizziness, and syncope due to rise in left atrial pressure and lower stroke volume.

Structural heart conditions that predispose to atrial fibrillation and flutter, and are seen in pregnant patients, include mitral stenosis, congenital heart disease, and other conditions causing heart failure [65]. These conditions are described in detail separately:

●Mitral stenosis. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis".)

●Congenital heart disease [62] or preexisting heart failure. (See "Pregnancy in women with congenital heart disease: General principles".)

Another scenario that can present for the first time in pregnancy is conduction down an antegrade accessory pathway that produces rapid atrial fibrillation. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Atrial fibrillation'.)

A study of pregnancy-related hospitalizations (from 2000 to 2012) demonstrated that AF is the most frequent arrhythmia in pregnancy and the frequency has been increasing over time, and that maternal and/or fetal complications are more common in women with arrhythmias in general [4].

Diagnostic testing — As with the nonpregnant patient, atrial fibrillation and flutter can be associated with structural heart disease in females of childbearing age; thus, all pregnant patients presenting with these arrhythmias should have a thorough clinical investigation. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

The evaluation includes:

●History and physical examination.

●Electrocardiogram.

●Transthoracic echocardiogram.

●Continuous cardiac rhythm monitoring to assess arrhythmia burden and average heart rate.

●Search for any obvious provoking factor (eg, hyperthyroidism, electrolyte imbalances, pulmonary embolism, alcohol abuse) with treatment of the precipitant as necessary.

Management — Management, as with the nonpregnant patient, includes treatment of acute episodes, prevention of systemic embolization, and deciding on a rate versus rhythm control strategy. In the pregnant patient, it is important to discuss the labor and delivery plan as early as possible in pregnancy using a multidisciplinary team-based, shared decision-making approach.

We agree with the recommendations for pregnant patients made in the 2020 European Society of Cardiology (ESC) guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery [14] and the 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy [13,14].

Management of acute episodes — Much of the management of acute atrial fibrillation is similar in pregnant and nonpregnant persons.

●Hemodynamic instability – Episodes of atrial fibrillation and flutter that cause hemodynamic instability require emergent direct current (DC) cardioversion [13,48]. Atrial fibrillation with rapid ventricular rates in pregnant patients with preexcitation is also best treated with DC cardioversion. (See 'Electrical cardioversion' below.)

Some patients may require concomitant initiation of anticoagulation.

●No hemodynamic instability – For pregnant patients who are hemodynamically stable, either electrical or pharmacological cardioversion can be attempted. The choice of approach is discussed separately. (See "Atrial fibrillation: Cardioversion", section on 'Electrical versus pharmacologic cardioversion'.)

●Prevention of embolization – For patients in whom immediate cardioversion is not needed, it is important to recognize that if an episode of AF lasts more than 48 hours, or is of unknown duration, a transesophageal echocardiogram should be performed to rule out left atrial appendage thrombus, or systemic anticoagulation should be maintained for three weeks prior to electrical or pharmacologic cardioversion. Systemic anticoagulation is needed for at least four weeks following cardioversion [14]. This is discussed in detail separately. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'AF duration uncertain or 48 or more hours'.)

•Pharmacological cardioversion – In pregnant patients, flecainide (table 1) is used to achieve cardioversion [13,14]. In the pregnant patient, ibutilide is avoided after the first trimester, as there is little experience with its use [14]. Amiodarone is also avoided due to potential fetotoxicity [66,67].

●Obstetric care – For the pregnant patient with atrial fibrillation or flutter, decisions about hospitalization for an acute atrial fibrillation episode and whether to perform fetal monitoring should be coordinated with the obstetrics care providers.

Rhythm control versus rate control — During pregnancy, we prefer a rhythm control strategy for newly diagnosed atrial fibrillation and for patients who remain symptomatic with a rate-control strategy. This approach differs from nonpregnant patients, where more consideration is given to pursuing rate control, particularly in patients without structural heart disease. This is discussed separately. (See "Management of atrial fibrillation: Rhythm control versus rate control".)

●Rhythm control – Flecainide in the absence of structural heart disease or sotalol in the absence of left ventricular systolic dysfunction should be considered to prevent atrial fibrillation if AV nodal-blocking drugs fail [13,14,48]. Amiodarone is not typically used in pregnancy due to its potential fetal teratogenic effects. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".)

●Rate control – If rhythm control cannot be achieved or is unlikely to be successful, then ventricular rate control can be instituted. In pregnant patients, beta-selective blockers are recommended for rate control [13,14,48]. If beta blockers fail, digoxin or verapamil should be considered. These are used alone or in combination to control the ventricular response rate [68]. Amiodarone is not typically used in pregnancy due to its potential fetal teratogenic effects. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".)

Anticoagulation — Pregnancy is associated with a prothrombotic state and increased thromboembolic risk. However, risk stratification for stroke in atrial fibrillation has not been extensively studied in regard to pregnant patients; only one small retrospective study demonstrated that the CHA₂DS₂-VASc score may underestimate the risk of stroke in pregnant patients [69].

Anticoagulation is recommended for stroke prevention in pregnant patients with atrial fibrillation or flutter and additional thromboembolic risk factors as in the nonpregnant patient [48]. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'CHA2DS2-VASc score' and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.)

●Preferred anticoagulant – The preferred anticoagulant for most patients is low molecular weight heparin. Heparin can be used throughout all stages of pregnancy but should be discontinued prior to delivery. (See "Use of anticoagulants during pregnancy and postpartum" and "Use of anticoagulants during pregnancy and postpartum", section on 'LMW heparin' and "Use of anticoagulants during pregnancy and postpartum", section on 'Timing for starting LMW heparin'.)

Management of antithrombotic therapy for pregnant patients with prosthetic heart valves is discussed in detail separately. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

Warfarin is often not used in pregnancy because of the risk of embryopathy and fetopathy. Similarly, novel oral anticoagulants are not recommended during pregnancy because of the lack of safety data and the potential fetal toxicity at high doses [13,14]. (See "Use of anticoagulants during pregnancy and postpartum".)

Labor and delivery plan — If a patient is on anticoagulation, it should be held at the time of labor and delivery.

It is reasonable to obtain a 12-lead electrocardiogram upon arrival to labor and delivery. If the patient is in atrial fibrillation, they have had a high burden of atrial fibrillation, they have had problems with rate control, or there is structural heart disease, the use of telemetry is reasonable in order to monitor heart rate and rhythm.

Close coordination between the patient and multidisciplinary cardio-obstetrics team (including cardiology, high-risk obstetrics, maternal fetal medicine, neonatology, social work, and anesthesia providers) to develop the labor and delivery plan for patients with atrial fibrillation and flutter is important [70,71]. (See "Acquired heart disease and pregnancy", section on 'Management of labor and delivery'.)

ISSUES REGARDING ANTIARRHYTHMIC DRUG TREATMENT — The rate of placental passage of any drug is dependent on lipid solubility, molecular weight, protein binding, ionization, fetal and placental blood flow, and pH of maternal and fetal fluids. Nonionized, nonprotein bound, lipid soluble drugs with molecular weight below 600 Daltons freely cross the placenta [72], while high molecular weight drugs are not transported in significant amounts. Almost all antiarrhythmic drugs cross the placenta. Fetal tissues begin to differentiate during the period of organogenesis (gestational weeks 5 to 10) and are most susceptible to the effects of teratogens at that time. The major concern with antiarrhythmic drugs taken during the second and third trimesters are potential adverse effects on fetal growth and development, drug-related side effects in the neonate, risk of proarrhythmia, and possible effects on uterine contractility.

Safety during pregnancy — Safety profiles of antiarrhythmic drugs are drawn from case reports, case series, registry data, and case control and cohort studies of pregnant patients treated with these drugs, alone or with other agents, and for a variety of indications, including hypertension, maternal or fetal arrhythmias, and a wide spectrum of underlying medical disorders, which could confound findings. There are no data from large well-designed randomized trials on which to base a recommendation for use of one drug over another. Data regarding both comparative efficacy in improving maternal outcome and fetal safety are inadequate for almost all antiarrhythmic drugs.

Information related to the toxicity and teratogenicity of medications in pregnant patients must be interpreted in light of the background risk of adverse pregnancy outcomes in any pregnant woman. Major birth defects are defined as events of medical, surgical, or cosmetic significance. It is estimated that the prevalence of major birth defects is 2 to 4 percent among live born infants, and in utero growth restriction occurs in 3 to 10 percent of pregnancies, depending on the definition used. Intrauterine growth restriction can be related to in utero drug exposure, the mother's disease, other drug therapy, or a combination of these and other factors (eg, intrinsic fetal or placental factors).

Since 1975, the United States Food and Drug Administration (FDA) has assigned pregnancy risk factors to all drugs available in the United States. Information on the use of specific drugs in pregnancy, including the FDA risk category and pregnancy implications, is available in the UpToDate drug database. Specific information on the fetal and neonatal risks of maternal drug ingestion during pregnancy and lactation are also available from the following website: www.perinatology.com/exposures/druglist.htm.

The following table provides a brief synopsis of pregnancy and breastfeeding implications for the drugs discussed in this topic (table 1).

Pharmacokinetic changes during pregnancy — Physiological changes during pregnancy may alter the absorption, excretion and effective plasma concentration of all antiarrhythmic drugs. Increased intravascular volumes during pregnancy may require an increase in loading dose. Gastrointestinal absorption of drugs may be altered by changes in gastric secretion and intestinal motility. Increase in renal blood flow and progesterone-induced increase of hepatic metabolism may augment drug clearance [73]. Finally, decreased serum protein concentrations may reduce protein binding, decreasing the total drug concentration and leading to greater fluctuation in unbound drug concentration. These pharmacokinetic changes may explain why pregnant patients previously stable on antiarrhythmic therapy have breakthrough arrhythmias. Because of intra-individual variability in the above-mentioned factors, drug dose should be optimized on an individual basis with monitoring of clinical response.

Breast feeding — In general, drugs that are most likely to be transferred from maternal plasma to milk have the following characteristics: nonionized, nonprotein bound, low molecular weight, high lipid solubility, and high pH. In addition to drug transfer, drug clearance in the setting of a neonate's immature renal and hepatic function also determines whether a drug and/or its metabolites reach therapeutic or toxic levels in the infant.

The LactMed database, produced by the National Library of Medicine, provides monographs on many prescription and over-the-counter medications. The database is available free of charge. The UpToDate drug database also provides information on lactation and breastfeeding implications for all drugs in the database.

The following table provides a brief synopsis of pregnancy and breastfeeding implications for drugs discussed in this topic (table 1).

ISSUES REGARDING NON-PHARMACOLOGIC TREATMENT

Electrical cardioversion — Emergent or elective electrical cardioversion can be performed at all stages of pregnancy [13,48,74], and should be used for any sustained arrhythmia with hemodynamic compromise and can be considered for drug-refractory arrhythmias. In the third trimester, some physicians prefer to perform electrical cardioversion under general anesthesia and intubation, considering the more difficult airway and increased risk of gastric aspiration during pregnancy. Electrical cardioversion does not result in compromise of blood flow to the fetus [74]. While there is a theoretical risk of inducing an arrhythmia in the fetus, this risk is very small due to the high fibrillation threshold and small amount of energy reaching the fetus. Nonetheless, postprocedure continuous electronic fetal heart rate monitoring is recommended because of reported cases of emergency cesarean delivery due to fetal arrhythmias [75].

In one multicenter study, 27 pregnant females had 29 electrical cardioversions for supraventricular arrythmias (atrial fibrillation [44 percent], atrial flutter [30 percent], SVT [19 percent], atrial tachycardia [7 percent]) [76]. There were no maternal or fetal deaths. Median gestation at cardioversion was 28 weeks, and median gestation at delivery was 35 weeks. Postprocedure fetal monitoring was undertaken following cardioversion in nearly half the patients and in 7 percent, urgent delivery was required postcardioversion due to fetal bradycardia.

Radiofrequency catheter ablation — In nonpregnant patients, more definitive treatment of atrial fibrillation, atrial flutter, and other arrhythmias can be accomplished with catheter ablation. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Introduction'.)

Catheter ablation prior to pregnancy is recommended in patients with symptomatic arrhythmias [11]. Ablation of atrial flutter and other arrhythmias is generally avoided during pregnancy given the need for fluoroscopy. For those experiencing new onset of arrhythmias suitable for radiofrequency ablation, or worsening of existing arrhythmias during pregnancy, ablation is generally delayed until after delivery.

Experience with radiofrequency catheter ablation during pregnancy has been limited to cases of supraventricular tachycardia [54,57,77-84]. These procedures are generally not performed during pregnancy, mainly due to concerns of ionizing radiation exposure to the fetus. However, in rare cases, patients with severe and drug-resistant arrhythmias during pregnancy may be considered for an ablation procedure [11,13,48]. The risk of radiation exposure for the fetus during a typical ablation is small (<1 mGy at all periods of gestation), and is mainly attributable to scatter from the thorax of the mother [85]. (See "Diagnostic imaging in pregnant and lactating patients".)

Cases of successful ablation of atrial tachycardia using intracardiac echocardiography and electro-anatomic mapping without fluoroscopy have been reported [86,87].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".)

SUMMARY AND RECOMMENDATIONS

●Symptoms – Palpitations occur frequently during pregnancy and are a common indication for cardiac evaluation during pregnancy. (See 'Symptom-rhythm correlation' above.)

●Evaluation for structural heart disease – Since cardiac arrhythmias are frequently associated with structural heart disease, any woman who presents with an arrhythmia during pregnancy should undergo clinical evaluation for structural heart disease. including an electrocardiogram and a transthoracic echocardiogram. (See 'Diagnostic testing' above.)

●Paroxysmal supraventricular tachycardia – In pregnant patients with structurally normal hearts, paroxysmal supraventricular tachycardia (PSVT), including atrioventricular (AV)-nodal reentrant tachycardia and AV-reciprocating tachycardia, is the most common arrhythmia. Management of PSVT is performed with AV-nodal blocking agents. If hemodynamic compromise is evident, direct current (DC) cardioversion should be performed. (See 'Paroxysmal supraventricular tachycardia' above.)

●Atrial fibrillation and flutter – These arrhythmias occur less frequently than PSVT and are more common in patients with structural heart disease. (See 'Atrial fibrillation and flutter' above.)

•Hemodynamically unstable pregnant patients require urgent cardioversion. (See 'Electrical cardioversion' above.)

•We suggest a rhythm control over a rate control strategy in pregnancy (Grade 2C). In pregnant patients, we use flecainide, propafenone, or sotalol (table 1). (See 'Rhythm control versus rate control' above.)

•If rhythm control cannot be achieved or is unlikely to be successful, then ventricular rate control can be instituted. Rate-control agents in pregnancy include beta-selective blockers, verapamil, and digoxin (table 1), either alone or in combination.

•Although pregnancy is a prothrombotic state, given the lack of extensive data on risk stratification during pregnancy, similar recommendations for stroke risk assessment should be used as those in nonpregnant patients. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".)

•The preferred anticoagulant for most pregnant patients is low molecular weight heparin. Heparin can be used throughout all stages of pregnancy but should be discontinued prior to delivery. (See 'Anticoagulation' above.)

●The labor and delivery plan – Pregnant patients with arrhythmia should develop an early birth/labor plan with their multidisciplinary team including cardiology, OB-GYN, and anesthesia. A 12-lead electrocardiogram upon arrival to labor and delivery and telemetry may be indicated. (See 'Labor and delivery plan' above.)

●Information on the use of specific antiarrhythmic drugs in pregnancy is available in the UpToDate drug database. (See 'Issues regarding antiarrhythmic drug treatment' above.)