Management of tachyarrhythmias in pregnancy – A review

Abstract

The most common arrhythmias detected during pregnancy include sinus tachycardia, sinus bradycardia, and sinus arrhythmia, identified in 0.1% of pregnancies. Isolated premature atrial or ventricular arrhythmias are observed in 0.03% of pregnancies. Arrhythmias may become more frequent during pregnancy or may manifest for the first time.

Evaluation of the ECG

The 12-lead ECG can offer important clues to the underlying etiology of arrhythmias, and should be examined for delta waves, indicating ventricular preexcitation, evidence of prior myocardial infarction, conduction delay or bundle branch block, hypertrophy, and QTc prolongation or T wave inversion. Any baseline abnormality of the 12-lead ECG may suggest underlying cardiac disease and should prompt further evaluation.

Important features of the ECG during tachycardia include the rate of ventricular response, QRS width (<120 ms considered “narrow complex”), regularity of the QRS morphology, and atrioventricular (AV) relationship. A wide complex tachycardia may represent ventricular tachycardia (VT), supraventricular arrhythmia with preexcitation over an accessory pathway (AP), or aberrant conduction (block in right or left bundle branch). Aberrant conduction can be either a preexisting abnormality or a rate-related phenomenon. Criteria exist for the discrimination between VT and supraventricular tachycardia with aberrant conduction or ventricular pre-excitation. The most helpful ECG findings indicating VT are the presence of capture and fusion beats, and AV dissociation.^1,2

Supraventricular arrhythmia in the absence of structural heart disease

Supraventricular tachycardia (SVT) is a heart rhythm where atrial rate exceeds 100/min at rest. These arrhythmias typically have a narrow QRS complex, although aberrancy may be observed. The SVTs include atrial tachycardia, atrial flutter, junctional tachycardia, AV nodal reentrant tachycardia (AVNRT) and AP-mediated atrio-ventricular reentrant tachycardias (AVRT). The pathophysiology and management of atrial fibrillation differs from that of simple SVTs and will be considered separately.

SVT will complicate 0.02–0.5% of pregnancies,^3,4 and for 50% of women, this will be the first presentation.^3,5 Women with preexisting SVT are likely to experience worsening of arrhythmia (50%), with an increase in adverse neonatal or fetal event rates, in the range of 8% including premature birth, small for gestational age (SGA) and respiratory distress syndrome (RDS).⁶

Inappropriate sinus tachycardia

Inappropriate sinus tachycardia (IST) is defined as sinus rhythm with rates exceeding 100/min at rest, with average daily heart rate exceeding 90/min. IST can be difficult to distinguish from the physiologic heart rate changes of pregnancy, where the average sinus rate increases steadily through each trimester, and reach a peak in the third trimester.^7–9 It is a diagnosis of exclusion, made after examination of the ECG and Holter monitor to exclude atrial tachycardia and exclusion of secondary causes such as thyrotoxicosis, anemia, infection, pulmonary embolism and substance abuse or withdrawal. Features supportive of IST are P wave axis and morphology identical to normal sinus rhythm and some suppression of tachycardia during sleep.¹⁰ The prognosis of IST is excellent, and in most cases can be managed conservatively.^11,12 Treatment with beta blockade is frequently ineffective and may be limited by relative hypotension or fatigue.¹¹ Ivabradine is emerging as the mainstay of therapy for IST in the non-pregnant population. Ivabradine is not recommended during pregnancy due to potential teratogenicity.¹³ Supportive measures and reassurance are the most important aspects of IST management.

Atrial tachycardia

Focal AT is an organized atrial tachyarrhythmia with a generally regular rate, although periods of acceleration and deceleration can be seen, particularly at onset and termination of tachycardia.¹⁴ The ECG shows discrete P waves, separated by an isoelectric segment (Figures 1 and 2). P wave morphology depends on the site of the arrhythmia focus. Multifocal atrial tachycardia (MAT) is a rare form of SVT characterized by multiple (>3) distinct P wave morphologies, and is irregular, owing to the multiple origins of atrial impulses.¹⁵

Figure 1.

ECG showing focal atrial tachycardia with 2:1 AV conduction in pregnant female.

Figure 2.

ECG showing resumption of normal sinus rhythm in same pregnant female after catheter ablation of a right atrial appendage focus, featured in Figure 1. Note the difference in P wave morphology, making IST extremely unlikely diagnosis.

Junctional tachycardia

Junctional tachycardia (JT) is a rare form of SVT resulting from automaticity at the AV junction.¹⁶ When documented, it is typically in the pediatric setting or post-cardiac surgery. It is exceptionally uncommon in adults.¹⁷ In this tachycardia, the atrial activity in the form of a retrograde P wave is typically obscured by the QRS complex on the ECG.

AV nodal reentrant tachycardia and AV reentrant tachycardia

AVNRT and AVRT occur with equal frequency in the pregnant population.⁴ In AVNRT, the atria and ventricles are activated nearly simultaneously, and atrial activity in the form of a retrograde P wave is either obscured by the QRS complex on the ECG, or is inscribed shortly after the QRS complex, manifesting as a “pseudo R’ wave” in lead V1, or “pseudo S wave” in the inferior leads (Figure 3). Symptoms typically have an abrupt onset and offset.

Figure 3.

ECG showing AVNRT in pregnant female, with classic findings of retrograde atrial activity as rSR’ in V1, and pseudo-S waves in inferior leads (II, III, aVF).

AVRT depends on the presence of an accessory pathway (AP), a congenital remnant of conducting tissue between the atria and ventricles that bypasses the AV node. Antegrade conduction results in a short PR interval and evidence of preexcitation in the form of a delta wave on the surface ECG. A proportion of APs have only retrograde conduction and are therefore “concealed” with no evidence of preexcitation on the baseline ECG.¹⁸ Ebstein’s anomaly is a rare form of CHD that may be associated with multiple AP, atrial fibrillation and AVRT.¹⁹ The presence of ventricular preexcitation may be predictive of adverse cardiac outcomes in pregnancy.²⁰

Management of SVT – No structural heart disease (see Table 1)

Table 1.

Commonly used drugs for arrhythmia management in pregnancy.

Drug	Pregnancy category	Placental transfer	Notes – Use in pregnancy	Present in breast milk	Protein bindinga	Renal clearanceb	Notes – Use during breastfeedingc	Reference
Adenosine	C	No	Fetal bradycardia has been described.	Unknown	NA	NA	Limited data in breastfeeding, likely safe.	25,32,33
Digoxin	C	Yes	First line agent for SVT management in pregnancy. Serum levels not reliable in pregnancy. Based on available data, an increased risk of adverse pregnancy outcomes has not been observed.	Yes Low risk of accumulation in neonates after oral dosing.	25%	57–80%	Not expected to have adverse effect in breastfed infant. The relative infant dose (RID) of digoxin is 1% to 7% of a weight-adjusted maternal dose or 0.2% to 4% of a neonatal maintenance dose.	33,34
Class IA antiarrhythmic drugs
Procainamide (IV)	C	Yes	Recommended for acute termination of pre-excited tachycardia. May be used for termination of refractory SVT. Associated with maternal lupus-like syndrome with prolonged use, possible QT prolongation.	Yes High risk of accumulation in neonates.	15–20%	>80% (including active metabolite)	Scant data. Use with caution in breastfeeding women, especially with longer term use.	33,35
Class IB antiarrhythmic drugs
Mexiletine	C	Yes	Limited data. Probably safe for management of VA.	Yes Low risk of accumulation in neonate.	50–60%	10%	Use during breastfeeding is not recommended. The relative infant dose (RID) of mexiletine is lesser than 2% of the maternal weight-adjusted dose.	33,36 37
Lidocaine (IV)	B	Yes	Lidocaine IV used for management of VA.	Yes Low risk of accumulation in neonate.	60–70%	<10%	Poorly absorbed by infant. Not expected to cause any adverse effects in breastfed infants.	33,38
Class IC antiarrhythmic drugs
Flecainide	C	Yes	Recommended for the prevention of SVT in women with Wolff-Parkinson-White (WPW) syndrome, or for control of atrial rhythm in AF/Flutter, and select cases of VA.	Yes Low risk of accumulation in neonates after oral dosing.	40%	30%	Not expected to have adverse effect in breastfed infant, especially after two months of age. The relative infant dose (RID) of flecainide is 3.6% of the maternal weight-adjusted dose.	39,40 33,41,42
Propafenone	C	Yes	Recommended for the prevention of SVT in women with Wolff-Parkinson-White (WPW) syndrome, or for control of atrial rhythm in AF/Flutter.	Yes Low risk of accumulation in neonates after oral dosing.	90%	50%	Scant data. Use with caution in breastfeeding women. The relative infant dose (RID) of propafenone is lesser than 1% of the maternal weight-adjusted dose.	33,43
Class II antiarrhythmic drugs: Beta blockers	Class effect evident in all beta blockers, with increased risk of growth restriction and preterm delivery as well as neonatal bradycardia and hypoglycemia.							44,45 33,46
Atenolol	D	Yes	Associated with significant IUGR.	Yes High risk for accumulation in neonates.	10%	85%	Consider avoiding use until breastfed infant is greater than three months of age. The relative infant dose (RID) of atenolol is 3–35%, depending on postpartum age and maternal dose.	47,48 33,49,50
Bisoprolol	C	Yes	First line agent for SVT management in pregnancy. Generally considered safe.	Yes Moderately high risk of accumulation in neonates.	30%	50%	Very little data to support safety in breastfed infants.	33,51–53
Carvedilol	C	Yes	Low risk of growth restriction.	Yes Low risk of accumulation in neonates.	95%	1%	Not well studied. Other beta blockers should be considered during breastfeeding.	33,54
Metoprolol	C	Yes	First line agent for SVT management in pregnancy. Well tolerated. Substantial increase in clearance in T2/T3 up to three months post-partum.	Yes Moderately low risk for accumulation in neonates.	10%	40%	Not expected to have adverse effect in breastfed infants. The relative infant dose (RID) of metoprolol is 7% when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 100 mg/day.	33,55
Propranolol	C	Yes	First line agent for SVT management in pregnancy. Generally considered safe.	Yes Low risk of accumulation in neonates.	87%	<1%	Not expected to have adverse effect in breastfed infant. The relative infant dose (RID) of propranolol is 0.2–0.9% of the maternal dose.	33,56,57
Class II/III antiarrhythmic drug: Sotalol	B	Yes	Used as second line agent for management of refractory atrial and ventricular arrhythmias. Caution regarding QT prolongation, reduced renal function, established heart failure. Initiation requires hospital admission for ECG monitoring.	Yes High risk of accumulation in neonate.	None.	80–90%	Breastfeeding not recommended during therapy, especially infants lesser than three months of age. If infant is breastfed, infant should be monitored for bradycardia, QT prolongation. The relative infant dose (RID) of sotalol is 35% when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal oral dose of 600 mg/day.	33,58–60
Class III antiarrhythmic drug: Amiodarone	D	Yes	Use can be considered for refractory, life-threatening arrhythmia. Fetal/neonatal risks include bradycardia, QT prolongation, arrhythmia, neonatal hypothyroidism, hyperthyroxinemia. Neurodevelopmental abnormalities independent of thyroid function have been reported. Fetal growth retardation and/or premature birth.	Yes High risk of accumulation in neonate.	>96%	<1%	Breastfeeding not recommended during therapy. If infant is breastfed, infant thyroid function should be monitored. The relative infant dose (RID) of amiodarone is 3.5–45% of the weight-adjusted maternal dose (including the active metabolite desethylamiodarone). Due to its long half-life, amiodarone and its metabolite may be present in breast milk for weeks following discontinuation of therapy. Periodic monitoring of infant cardiac and thyroid function status recommended.	61,62 33,51,63
Antiarrhythmic Class IV calcium channel blockers
Verapamil	C	Yes	Preferred non-dihydropyridine calcium channel blocker for arrhythmia management. May cause maternal hypotension, bradycardia.	Yes Low risk of accumulation in neonates.	90%	<2%	No adverse neonatal effects reported. May cause maternal hyperprolactinemia, galactorrhea.	64,65 33
Diltiazem	C	Yes	Avoid in first trimester. Animal studies suggest possible skeletal malformation, low birth weight.	Yes Low risk of accumulation in neonates.	70–80%	2–7%	Scant data. The relative infant dose (RID) of diltiazem is 0.9% of the weight-adjusted maternal dose. Not expected to have adverse effect in breastfed infant.	66,67 33

Pregnancy category: (A) No demonstrated risk to the fetus based on well-controlled human studies; (B) No demonstrated risk to the fetus based on animal studies; (C) Animal studies have demonstrated fetal adverse effects, no human studies, potential benefits may warrant use of the drug; (D) Demonstrated human fetal risk, potential benefits may warrant use of the drug; (X) Demonstrated high risk for human fetal abnormalities outweighing potential benefit; (N) Nonclassified.

^aPresence of drugs in breast milk depends on the degree of protein binding of the drug. Drugs with lower protein binding are excreted to a greater degree into breast milk.

^bAccumulation of a drug in a neonate is determined by renal excretion of the drug.

^cIn general, breastfeeding is considered acceptable when the RID of a medication is lesser than 10%.⁶⁸

The potential adverse effects of both medical therapy and poorly controlled arrhythmia should be considered when making management decisions in the pregnant woman. In general, the established guidelines for SVT management apply in the pregnant woman.¹² Initial management of an acute regular, narrow complex tachycardia is an attempt at vagal maneuvers.^21,22 Valsalva maneuver is the most effective of vagal maneuvers, terminating tachycardia in up to 43% of women with a modification in which the maneuver is performed seated, followed by an abrupt move to the supine position with legs elevated.²³ Other effective vagal maneuvers include induction of the diving reflex with application of an ice-cold towel to the face, or immersion of the face in cold water.^22,24 Adenosine, administered in doses of 6–24 mg pushed rapidly via proximal intravenous line, is effective at terminating maternal SVT, with success rates well over 80%.^3,25 Adenosine may also unmask atrial activity in the setting of atrial flutter (AFl) or AT.^12,26 The most common adverse effects include chest discomfort and shortness of breath, but these are transient as the half-life of adenosine is very short due to rapid metabolism by red blood cell adenosine deaminase.^12,27,28 Adenosine may be used safely in pregnancy with no adverse fetal effects.^3,25,29–31

Alternative agents for management of acute, regular SVT include the slow intravenous administration of calcium channel blocking agents verapamil or diltiazem, which may terminate SVT in 64–98% of women.^21,69–72 These agents must not be used in the setting of ventricular dysfunction and care must be taken to exclude the possibility of ventricular preexcitation or VT, as this may lead to hemodynamic instability or ventricular fibrillation.^12,73,74

Management of SVT for the duration of pregnancy depends on the frequency of episodes and their hemodynamic impact, and in many cases conservative management is appropriate. For women with intermittent SVT, without evidence of ventricular pre-excitation, oral beta blockers or calcium channel blockade may reduce the frequency and severity of SVT.^12,75,76 For women requiring higher doses of AV nodal blocking agents, digoxin may be a useful adjunct therapy.^76,77 If these agents fail, class I antiarrhythmic agents can be considered as second-line therapy. There is evidence to support the efficacy of propafenone and flecainide for arrhythmia prophylaxis.^72,78–84 Sotalol, a beta blocker also considered class III antiarrhythmic agent is also effective in management of SVT,¹² however the proarrhythmia risk precludes routine use for first-line arrhythmia prophylaxis. American College of Cardiology, American Heart Association and European Society of Cardiology (ACC/AHA/ESC) guidelines for the management of SVT recognize catheter ablation as a reasonable management option (class IIb) for refractory arrhythmias in pregnancy, as long as efforts are made to reduce radiation exposure.¹²

Antiarrhythmic therapy is indicated for the management of atrial tachycardia when the ventricular rate cannot be adequately controlled with AV nodal blockade.^12,17 Flecainide and propafenone are effective antiarrhythmics that should be combined with an AV nodal blocking agent.^85,86 Sotalol can be effective as a solitary agent.⁸⁷ Synchronized cardioversion may not be effective in the absence of antiarrhythmic therapy, particularly in the setting of an automatic focal atrial tachycardia, as atrial tachycardia may resume.^88,89

Atrial flutter and atrial fibrillation

Atrial fibrillation (AF) is a disorganized atrial arrhythmia frequently associated with rapid ventricular rates and atrial dysfunction. P waves are absent on the electrocardiogram, and rhythm is irregular. Atrial flutter (AFl) is a macro reentrant tachycardia with a characteristic ECG appearance of “sawtooth” flutter waves. AF/AFl are uncommon in women without structural heart disease.^3,6 More than half of women with established paroxysmal AF are at risk for recurrence in pregnancy.⁶ The adverse neonatal or fetal event rate is 35% in women with paroxysmal AF/AFl and as high as 50% in women with persistent AF/AFl.⁶

The thromboembolic risk in AF/AFl in the absence of structural heart disease is low in the pregnant woman and systemic anticoagulation is not always required.³³ However, left atrial thrombus has been reported in this setting.⁹⁰ The established risk-scoring systems, (CHADS2 or CHA₂DS₂VASC score)^91,92 have not been validated for use in pregnancy, but may be useful to estimate thromboembolic risk. A history of hypertension, congestive heart failure, vascular diseases, diabetes, advanced age, and prior cardioembolic events are important risk factors. The choice of anticoagulant depends on the stage of pregnancy and underlying cardiac disease. In the first trimester and in the last four weeks of pregnancy, subcutaneous weight-adjusted LMWH is recommended, as it does not cross the placenta. Warfarin or LMWH are given in the second trimester until four weeks before anticipated delivery date. This minimizes the risk of teratogenicity and neonatal hemorrhage³³⁹³ (see Figure 4). Anticoagulants such as rivaroxaban, apixaban and dabigatran have not been studied for use in pregnancy and only limited data on fetal exposure exists.⁹⁴ At this time, these agents should not be used in pregnancy.

Figure 4.

Flowchart for management of atrial fibrillation and anticoagulation management in pregnancy.

AV nodal blocking drugs are employed to establish control of ventricular rate.⁹⁵ Beta blockers are first line therapy, and digoxin can be added to optimize rate control, but is not as effective for rapid ventricular rates associated with physical stress.^96,97 Digoxin dose should be titrated to adequate control of resting ventricular rate while in AF, at rest, as measured levels are not reliable in pregnancy due to circulating immunoreactive serum components.⁹⁸ Verapamil is the second agent of choice for AV nodal blockade.^33,93 Randomized studies addressing the benefit of atrial rhythm control compared to control of ventricular rate in pregnancy are lacking.

AF/AFl of less than 48 h duration can be managed with immediate cardioversion, in the absence of structural heart disease or thromboembolic risk factors.^33,93 Sustained AF/AFl of unknown or greater than 48 h duration carries a risk of thromboembolism.⁹⁹ In this case, cardioversion should be preceded by at least three weeks of anticoagulation prior to cardioversion (Figure 4). Alternatively, TEE can be performed to exclude intracardiac thrombus before cardioversion.^33,93 In all cases, anticoagulation should be considered for at least four weeks after cardioversion, unless another indication for anticoagulation mandates more prolonged therapy.⁹³

Supraventricular arrhythmia in structural heart disease

Supraventricular arrhythmias requiring treatment develop in up to 15% of women with structural heart disease during pregnancy.¹⁰⁰ Hemodynamic assessment is a critical component of arrhythmia evaluation in women with structural heart disease.^101,102 Risk factors for the development of supraventricular arrhythmias in this population include preexisting arrhythmia, mitral valve disease, beta blocker use prior to pregnancy, and left-sided structural lesions. Atrial arrhythmias during pregnancy are associated with increased pregnancy-related morbidity and mortality.^6,103 Women with structural heart disease are more vulnerable to intra-atrial reentry (IART), as a result of prior surgical intervention as well as chronic atrial dilatation and cardiomyopathic changes of the atria secondary to volume loading.^104,105 One should always have a high index of suspicion for IART in the pregnant ACHD woman with tachycardia.^33,93

Management of SVT in the presence of structural heart disease (see Table 1)

It is important to consider the severity of underlying structural heart disease, the hemodynamic impact of the arrhythmia and need for thromboprophylaxis. “Simple” congenital lesions include isolated congenital aortic or mitral valve disease (excluding parachute valve or cleft leaflet), mild pulmonic stenosis, and isolated (or repaired without residua) small ventricular septal defect, patent foramen ovale or small atrial septal defect.¹⁰⁶

In the setting of structural heart disease, sustained tachycardia may cause hemodynamic compromise and placental hypoperfusion, and sinus rhythm should be restored as soon as possible with pharmacologic or direct-current cardioversion, or overdrive atrial pacing.^107,108 In the setting of hemodynamic instability, immediate cardioversion should be undertaken regardless of underlying cardiac disease, anticoagulation status, or availability of fetal monitoring.^33,93

Pregnancy elevates baseline thromboembolic risk.¹⁰⁹ Intracardiac thrombus complicates atrial arrhythmia in a substantial proportion of women with structural heart disease.¹¹⁰ Women with atrial arrhythmia and high-risk congenital lesions such as prior intracardiac repair, cyanosis, Fontan palliation, or systemic right ventricle should be considered for systemic anticoagulation.¹¹¹ Women with mechanical valves will already have an indication for anticoagulation independent of their arrhythmia.³³

When IART or AF has been less than 48 h duration in women with simple structural heart disease, cardioversion can be undertaken immediately, but anticoagulation should be initiated at the time of cardioversion and continued for at least four weeks.⁹³ Women with moderate or complex structural heart disease should undergo TEE to exclude intracardiac thrombus prior to cardioversion.¹⁰⁸ With IART or AF of more than 48 h duration, a minimum of three weeks of anticoagulation prior to cardioversion is recommended unless thrombus can be excluded by TEE.¹⁰⁸ Atrial overdrive termination can be considered in women with an existing pacemaker or defibrillator with an atrial lead in place.¹⁰⁷ Anticoagulation should be considered for at least four weeks after cardioversion in all women, unless another indication for anticoagulation mandates more prolonged therapy.⁹³

Pharmacologic conversion of supraventricular arrhythmias must be considered with caution, recognizing the potential for bradycardia and the pro-arrhythmic effects of pharmacologic therapy, particularly in females.^112–116 Class IA and IC antiarrhythmic drugs should not be used in the setting of abnormal function of the systemic ventricle or coronary artery disease.¹⁰⁸ Sotalol may have a pronounced negative inotropic effect and should not be used in the setting of systemic ventricular dysfunction.

Control of atrial rhythm may be preferred in complex structural heart disease, where maintenance of atrio-ventricular synchrony will have a beneficial hemodynamic effect. Beta blockade is typically the first choice for arrhythmia management, with the advantage of reducing ventricular arrhythmias in high risk women.^117,118 Nondihydropyridine calcium channel blockers may also be effective at controlling ventricular rate. Chronic control of ventricular rate during IART or AF is critical, as rapid AV conduction has been associated with tachycardia induced cardiomyopathy, as well as sudden cardiac death in complex CHD.^117–121 Target ventricular rates reported in clinical trials have included a maximum resting heart rate of 80/min and 110/min with exertion.^{117,118,122,123}

In simple structural heart disease, flecainide and propafenone may be considered as first line agents for rhythm control.^108,124,125 Class I agents must not be used in the setting of coronary artery disease or systemic ventricular dysfunction.^117,118,126 Although there is some evidence to support sotalol use in adults with CHD,^102,127 meta-analyses suggest an association with increased all-cause mortality.^108,128,129 Amiodarone may be considered a first-line antiarrhythmic agent for maintenance of sinus rhythm in adults with moderate to severe structural heart disease.^{92,93,102,130,131} The incidence of fetal hypothyroidism after maternal amiodarone exposure is 23%, unrelated to the dose or duration of amiodarone therapy. It is typically a transient phenomenon.¹³² Goitre is less common, seen in only 13% of hypothyroid infants.^133,134 Developmental delay has been reported, even in the absence of hypothyroidism.¹³⁵ Additional time- and dose-dependent adverse maternal effects include thyroid dysfunction (3.7%), liver toxicity (1.2%), neurologic side effects (4.6%), bradycardia (3.3%), in addition to photosensitivity and corneal deposits.¹³⁶ CHD may confer a greater risk of thyroid dysfunction.¹³⁰ Pulmonary toxicity is a reported but very rare complication.¹³⁶ Torsades-des-pointes has been reported but is fortunately extremely uncommon.¹³⁷

Dofetilide, another class III antiarrhythmic agent, is a reasonable alternative to amiodarone.^{91,93,108,138} This has not been studied extensively in pregnancy and is classified as category C. There has been no association with increased mortality in women with recent myocardial infarction or reduced ejection fraction^139–143 It has been studied in a small series of CHD women with atrial arrhythmias, with reasonable success.¹⁴⁴ The adverse effect profile of dofetilide includes a risk of torsades des pointes (0.9–3.3%)^142,143 and should not be used if the QTc is prolonged at baseline (QTc ≥ 440 ms, or ≥ 500 ms in the setting of conduction delay). Dosing must be adjusted for creatinine clearance. Initiation of therapy should take place with at least 72 h continuous cardiac monitoring and should be adjusted if QTc increases by more than 15% after first dose, or if it exceeds 500 ms (550 ms if there is baseline conduction delay).^108,145

Ventricular arrhythmias

Ventricular arrhythmias (VA) presenting in pregnancy can vary from asymptomatic isolated premature ventricular beats, non-sustained VT (NSVT), or sustained VA resulting in syncope or sudden cardiac death. Sustained VAs are uncommon in pregnancy, complicating less than 0.01% of pregnancies.³ VAs are more common in women with structural heart disease.⁶ In women with a history of VT, arrhythmia recurrence is seen in 27% of pregnancies.^6,146,147 VAs in pregnancy are associated with a significant adverse neonatal and fetal event rate, predominantly pre-term delivery, in the range of 14%.⁶

A careful evaluation for peripartum cardiomyopathy must be undertaken when VA complicates the last six weeks of pregnancy or early post-partum period.^53,148–150 Basic testing should include a 12-lead electrocardiogram and echocardiogram for determination of the presence of structural heart disease. The resting 12-lead ECG can reveal primary arrhythmia syndromes (long QT syndrome, short QT syndrome, Brugada syndrome) or suggest underlying cardiomyopathy (hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy). Echocardiography is critical to establish presence of underlying structural heart disease, and to quantify LV systolic function.¹⁵¹ Structural heart disease is one of the most important predictors of outcome in the setting of maternal VA.^152,153

Ventricular arrhythmias in the absence of structural heart disease

Idiopathic VAs occur in the absence of structural heart disease and, include outflow tract (OT) VT, fascicular VT, and papillary muscle VT. The most common origins are the ventricular outflow tracts, with the majority arising from the right ventricular outflow tract (RVOT).^154–157 In this case, the ECG has characteristic QRS morphology with a left bundle branch block pattern and inferior axis. The observation of more than one VT morphology is uncommon and should prompt careful evaluation for underlying cardiomyopathy.¹⁵⁸ The mechanism of OT arrhythmia is predominantly triggered activity secondary to c-AMP-mediated delayed afterdepolarizations¹⁵⁹ that can be exacerbated by exercise and emotional stress. The course is typically benign, although life-threatening arrhythmias have been reported.^160,161 Verapamil-sensitive posterior fascicular VTs are the most common of the idiopathic left ventricular VAs, accounting for over 90%.¹⁶² The QRS complex in this tachycardia has a characteristic narrow RBBB morphology and superior axis.

Ventricular arrhythmias in the presence of structural heart disease

Arrhythmia mechanism and long-term prognosis is very different in the setting of structural heart disease. This encompasses congenital and valvular heart disease,^163–167 cardiomyopathy including peripartum cardiomyopathy (PPCM),¹⁶⁸ congenital heart disease,¹⁰⁸ and ischemic heart disease with prior myocardial infarction.¹⁶⁸ In PPCM, arrhythmia complications are seen in 18.7%, with 2.2% experiencing cardiac arrest in one study.¹⁶⁹ Hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are inherited cardiomyopathies with frequent adverse arrhythmia outcomes.^170–172 In HCM, 10% of pregnancies may be complicated by ventricular arrhythmia.¹⁷³ Adverse cardiovascular outcomes are more common in women with poor functional class (NYHA class ≤2) or heart failure symptoms prior to pregnancy.¹⁷³ In ARVC, rates of VA recurrence are not increased in pregnancy, in women already managed with beta blockade.¹⁷⁴ Worsening of RV function or arrhythmia is rare in ARVC. Women at highest risk of complications are those with major RV structural abnormalities prior to conception.^175–177

Ischemic heart disease in pregnancy is uncommon, with a reported incidence of 1 in 10,000 deliveries.^178–180 Spontaneous coronary artery dissection is the most common cause of myocardial infarction during pregnancy and the postpartum period.^181,182 Management of VA in the setting of ischemic heart disease should include general principles of optimizing heart failure and primary ischemia management.¹⁵⁰

The incidence of VA in CHD varies by complexity of the underlying lesion, the history of anatomic repair, and age at which repair was completed.¹⁸³ VA risk is greatest in more complex CHD such as Fontan circulation, D-transposition of the great arteries (D-TGA), L-transposition of the great arteries (L-TGA), double outlet right ventricle, Tetralogy of Fallot (ToF), Ebstein’s anomaly, aortic coarctation, and aortic stenosis.¹⁰⁸

Acute VA management (see Table 1)

The first line therapy for any hemodynamically stable, regular, monomorphic, wide complex rhythm is intravenous adenosine.¹⁸⁴ Any VT with hemodynamic instability should be treated with immediate cardioversion/defibrillation.³³ Electrical cardioversion can be considered in hemodynamically stable women, but antiarrhythmic medication can also be used.¹⁶⁸ A careful review for underlying causes of VA should be considered, as many antiarrhythmic drugs are contraindicated in congenital or acquired long QT syndrome, Brugada syndrome, or in the setting of most structural heart disease. In the absence of these contraindications, intravenous administration of procainamide or sotalol, can be used for acute VA termination.^{147,184–186} In the setting of renal insufficiency, procainamide dosing needs to be adjusted, and sotalol should not be used. Amiodarone is most effective at preventing recurrent VA, but has some efficacy in terminating acute VA.^187,188 Intravenous verapamil administration should be avoided unless the arrhythmia is known to be of supraventricular origin, given the risk of severe hypotension.^151,184 Overdrive pacing for recurrent arrhythmia or arrhythmias refractory to medical therapy can be effective.^184,189

Chronic management of ventricular arrhythmias in the absence of structural heart disease

In the absence of structural heart disease, long-term therapy is warranted for women who are symptomatic, or when the PVC burden exceeds 20–24%.^190–192 In the latter case, a high burden of ectopy may predispose to ventricular dysfunction, and suppression of arrhythmia, particularly in the setting of declining LV function, is critical.¹⁹³ The mainstay of therapy for arrhythmia prophylaxis is beta blockade.^{31,147,168,194} The exception is idiopathic fascicular LV VT, which typically responds well to calcium channel blockade. In this setting, verapamil is the drug of choice.¹⁶⁸ If beta blockade is not effective, or poorly tolerated, verapamil can be considered as an alternative first-line agent. Class IC antiarrhythmics (flecainide, propafenone) can be considered as second line agents in the absence of structural heart disease.¹⁶⁸

Chronic management of ventricular arrhythmias in the presence of structural heart disease

Management of the underlying cardiac disease is of central importance in optimizing therapy for and preventing recurrence of VAs.¹⁶⁸ Beta blockers are the only agents that have been shown in randomized trials to be both effective and safe for VA prophylaxis in the setting of any structural heart disease.^{146,195–197} Sotalol is effective at treating arrhythmia in ischemic heart disease but should be avoided in the setting of reduced ejection fraction or renal impairment.^{129,198–201} In this setting, amiodarone may be the treatment of choice.^168,201 Amiodarone can be used in cases of refractory arrhythmia not responding to first-line therapy¹³¹ and can be used without increasing mortality in individuals with reduced ejection fraction.²⁰² Class I agents should be avoided as there is no mortality benefit to their use, and certain agents (class IC) have been shown to increase mortality.^168,203 Catheter ablation can be considered during pregnancy in cases of arrhythmia refractory to medical therapy, but this should only be considered in a center with experienced operators, and with strong consideration of a non-fluoroscopic approach, if available.^204–206 Assessment for need for ICD implantation should be considered early, and the decision to implant an ICD should not be impeded by pregnancy.

Cardioversion in pregnancy

DC cardioversion is safe and effective during pregnancy and recommended for all women with signs of hemodynamic instability.^184,207 There are rare reports of fetal distress immediately after cardioversion, particularly in women with severe underlying structural heart disease. Therefore, if feasible, fetal monitoring during or as soon as possible after cardioversion should be considered, with the support of an obstetrics team if emergency caesarean section is required.²⁰⁷ Placement of the apex defibrillation electrode on the breast results in higher transthoracic impedance, which will reduce current flow. The apex electrode should be placed lateral to or underneath the breast.²⁰⁸ Because pregnancy does not change transthoracic impedance, the cardioversion and defibrillation energy recommended for adult defibrillation are appropriate for use during pregnancy.²⁰⁹

Catheter ablation for arrhythmias in pregnancy

Catheter ablation should be considered for arrhythmias detected prior to pregnancy to avoid arrhythmia exacerbation and the need for medical suppression during pregnancy.¹⁶⁸ Catheter ablation can be considered during pregnancy in cases of arrhythmia refractory to medical therapy, but this should only be considered in a center with experienced operators, and with strong consideration of a non-fluoroscopic approach, if available.^204–206 ACC/AHA/ESC guidelines for the management of SVT recognize catheter ablation as a reasonable management option (class IIb) for refractory arrhythmias in pregnancy, as long as efforts are made to reduce radiation exposure.¹² Exposure to radiation during catheter ablation is highly variable, ranging from 727 to 3884 cGy/cm² for simple AVNRT, and 925 to 23,429 cGy/cm² for more complex procedures to treat ventricular arrhythmias or atrial fibrillation.²¹⁰ Potential adverse fetal outcomes after radiation exposure depend on the dose of radiation exposure and gestational age at time of exposure. Fetal exposure to less than 50 mGy felt to represent minimal risk, whereas higher doses may increase the risk of organ malformation or childhood malignancy. Fetal risk is greatest when exposure occurs in the first trimester.^211,212 There is growing experience in many centers with the successful use of electroanatomic mapping without fluoroscopy for arrhythmia management, if needed urgently during pregnancy.^213–219 In these cases, fetal cardiac monitoring has been standard of care. Collaboration with a high-risk obstetric team and neonatology should be part of procedural planning, in the unlikely event that fetal distress arises during the procedure.

Cardiac telemetry in labor and delivery

The purpose of cardiac telemetry is to identify arrhythmia which may result in significant hemodynamic compromise or death if not immediately recognized. In general, these tachyarrhythmias include high-grade ventricular arrhythmia or atrial arrhythmias with rapid ventricular preexcitation, but any arrhythmia that has resulted in altered level of consciousness or hemodynamic instability should be approached with caution. There are no guidelines for cardiac rhythm monitoring in labor and delivery. Fortunately, intrapartum arrhythmias are extremely uncommon, even for women who might be considered higher risk, with a history of ventricular arrhythmia or preexcited tachycardia.^220–222 Women with a history of frequent PVCs with a burden exceeding 10% may have an increased rate of cardiovascular complications in the course of pregnancy,²²⁰ and consideration should be given to periodic rhythm monitoring and cardiac telemetry during labor in this group. A history of non-sustained or sustained ventricular arrhythmia, cardiac arrest, or pre-excited atrial fibrillation should prompt referral to a center capable of intrapartum telemetry monitoring. A woman with a history of syncope felt to be potentially arrhythmia-mediated should also have a comprehensive cardiac assessment with consideration of intrapartum rhythm monitoring.