Neither supraventricular nor ventricular tachyarrhythmias are uncommon during pregnancy.1,2 When they are diagnosed, patients, relatives and physicians are frequently worried about ectopic beats and sustained arrhythmias.3,4 One should question whether arrhythmias should be treated in the same way as they would be outside pregnancy because all commonly used antiarrhythmic drugs cross the placenta.5 The pharmacokinetics of drugs are altered in pregnancy and blood levels need to be checked to ensure maximum efficacy and avoid toxicity.6–8 The major concern about antiarrhythmic drug therapy during pregnancy is the potential adverse effects on the foetus. In addition, in every pregnant woman with an arrhythmia, foetal cardiac assessment is necessary because foetal tachyarrhythmias can occur alone or combined with tachyarrhythmias of the mother.9,10 For these reasons, treatment of cardiac arrhythmias in intensive care and emergency medicine is difficult during pregnancy. Correct therapy based on an understanding of the mechanism that caused the arrhythmia may not only be life-saving for the mother but also may play an important role for the foetus.11,12 The purpose of this article is to summarise new strategies for pregnant woman with supraventricular or ventricular tachyarrhythmias who require emergency treatment.
Maternal Arrhythmias During Pregnancy
Incidence and First Manifestation
Supraventricular or ventricular tachyarrhythmias can become more frequent or may develop for the first time during pregnancy.13 An increased incidence of cardiac arrhythmias has been reported during pregnancy in patients with and without identifiable heart disease.14 New onset or increased frequency of supraventricular or ventricular tachyarrhythmias has been reported during pregnancy in patients with pre-excitation syndromes or other causes.15 Increased sympathetic activity during pregnancy has been proposed as a mechanism for increased incidence of arrhythmias.1,16 The occurrence of cardiac tachyarrhythmias may also be related to physiological changes that occur during pregnancy, such as increased heart rate, decreased peripheral resistance and increased stroke volume.17 Lee et al.18 reported a low risk of first onset of paroxysmal supraventricular tachycardia (SVT) during pregnancy, with an incidence of 4%.
Of 107 patients with an accessory-pathway-mediated tachycardia, seven had the first onset of tachycardia during pregnancy. Of the 100 patients with atrioventricular (AV) nodal re-entrant tachycardia, one had the first onset of tachycardia during pregnancy. Ventricular tachycardia (VT) is rarely observed during pregnancy: Nakagawa et al.8 studied 11 pregnant woman who experienced new-onset ventricular arrhythmias during pregnancy. The onset of the first episode was distributed equally over the three trimesters. The authors concluded that various haemodynamic and neurohumoral changes associated with pregnancy play an important role in ventricular arrhythmogenesis.8 In women with well-known recurrent episodes of SVTs, 14 of the 63 patients (22%) with tachycardia in the pregnant and non-pregnant periods had exacerbation of symptoms during pregnancy.18 Similar observations have been reported by others.19,20
Types of Arrhythmia
Shotan et al14 assessed the relationship between symptoms and cardiac arrhythmias in 110 consecutive pregnant patients without evidence of heart disease referred for evaluation of palpitations, dizziness and syncope (group G I). These patients were compared with 52 consecutive pregnant patients referred for evaluation of symptomatic functional precordial murmur (group G II). Sinus bradycardia (heart rate <60bpm) recorded during Holter monitoring (1% in G I, 2% in G II; p=NS) and sinus tachycardia (heart rate >100bpm: 9% in G I, 10% in G II; p=NS) were relatively rare, whereas there was a high frequency of sinus arrhythmias in both groups (61% in G I, 69% in G II; p=NS). Isolated atrial premature beats (APBs) were seen in 56% of G I and 58% of G II patients (p=NS); complex APBs (5% GI and 0% G II; p=NS) or SVT (1% G I and 6% G II; p=NS) were observed rarely. Isolated ventricular premature beats (PVCs) were recorded in 49% of G I and 40% of G II patients (p=NS), whereas the incidence of multifocal PVCs was higher in G I (12%) than in G II patients (2%; p<0.05). VT or ventricular fibrillation (VF) was not recorded in any of the patients.14
Before initiating therapy, it is important to correctly diagnose the type and mechanism of the underlying arrhythmia so that the proper therapeutic modalities can be implemented. The pregnant patient with arrhythmias usually seeks medical attention because of ‘palpitations’, light-headedness, shortness of breath or anxiety. Clues for correct diagnosis and treatment come from findings during physical examination and correct analysis of the electrocardiogram (ECG).21 Knowing the ECG features of the different types of narrow (QRS width <0.12s) or wide (QRS width >0.12s) tachycardias, it is of extreme importance to obtain ECG documentation of the arrhythmia so that the pregnant woman can receive the correct treatment.
Foetal Arrhythmias During Pregnancy
In utero, all types of arrhythmia can occur. They are frequently intermittent and may disappear until delivery or the neonatal period.22,23 Foetal arrhythmias can carry a significant risk of morbidity and mortality, especially when arrhythmias cause hydrops fetalis, which is associated with foetal death or neurological damage.24,25 In 2003, in the Swiss prospective FETCH study there was an 11% incidence of arrhythmias in 433 foetal echocardiographic examinations (www.neonat.ch). Among these arrhythmias, supraventricular premature beats were present in 79%, atrial fibrillation (AF) in 2%, SVT in 15% and AV blocks in the remaining 4%. It has been reported that AV nodal re-entrant tachycardia, ectopic atrial tachycardia or atrial flutter (AFlut) are serious and threatening rhythm disorders in the human foetus.26 A foetal tachycardia of a moderate to high rate with 1:1 retrograde conduction and poor cardiac tolerance can be due to a junctional ectopic tachycardia.27 In contrast to arrhythmias with a heart rate >100bpm, high-degree AV block with persistent foetal bradycardia can occur in either normal hearts or those with structural diseases.28,29 There is a poor prognosis when high-degree AV block is associated with congenital heart disease. In some cases, the foetal congenital AV block is caused by QT prolongation or immune-mediated diseases.30
The description of intrauterine AFlut by Carr and McLure in 1931 is probably the first published report. Blumenthal et al. documented intrauterine arrhythmias with the use of foetal electrocardiography in 1968. Currently, foetal echocardiography is the best method and remains the cornerstone for in utero diagnosis of arrhythmias.31 It has been shown that the electrophysiological mechanisms of foetal supraventricular tachyarrhythmias can be clarified with superior vena cava/aorta Doppler flow recordings.32 Cross-sectional echocardiography, M-mode and echo-Doppler have been used for differentiation of supraventricular from ventricular arrhythmias. Conventional foetal echocardiography views of the heart were obtained to exclude structural heart malformation. It is possible to determine the atrial rate using M-mode echocardiography, while the ventricular rate is determined with the use of M-mode and/or echo-Doppler.
Acute Therapy of Supraventricular Arrhythmias in the Pregnant Woman
Narrow-QRS-complex tachycardia is a cardiac rhythm with a rate faster than 100bpm and a QRS duration of less than 0.12s.21 The patient with narrow-QRS-complex tachycardia usually seeks medical attention because of palpitations, light-headedness, shortness of breath or anxiety. In many patients with narrow-QRS-complex tachycardia, the tachycardia rate is very high (180–240bpm); therefore, after onset of the tachycardia the patient will arrive very soon thereafter in an intensive care unit for diagnosis and treatment. The definitive diagnosis of narrow-QRS-complex tachycardia can be made in most patients based on the 12-lead ECG and clinical criteria. Acute treatment should be initiated based on the underlying mechanism. In regular narrow-QRS-complex tachycardia (QRS width <0.12s), vagal manoeuvres should be initiated to terminate the arrhythmia or to modify AV conduction.21,33 If this fails, adenosine or calcium channel blockers (verapamil) are the drugs of first choice (see Figure 1). Specific antiarrhythmic drugs should be avoided whenever possible in these conditions, because all commonly used antiarrhythmic drugs cross the placenta and may cause serious side effects to the foetus.
The advantage of adenosine 9–18mg intravenous (IV) as bolus relative to intravenous calcium antagonists or beta-blockers relates to its rapidity of onset and short half-life.34 In addition, the current reported human clinical experience with adenosine during pregnancy indicates no teratogenicity or other adverse effects to the foetus, and it is as effective in terminating SVT (efficacy rates >90%) in pregnant woman as it is in patients who are not pregnant. Longer-acting agents (IV calcium channel blockers or cardioselective beta-blocking agents) are of limited value because of a possible increase of hypotensive and/or bradycardiac effects.10 In patients with AV nodal re-entrant tachycardia, IV calcium channel blockers are acceptable drugs. The greatest experience has accrued with verapamil 10mg IV over three minutes, 5mg IV in woman with previous beta-blocker therapy and/or hypotension (RRsyst <100mmHg).
Clinical studies of verapamil in pregnant woman have not demonstrated adverse effects on either patient or foetus. However, IV administration of verapamil carries a risk of precipitating maternal hypotension and secondary hypoperfusion. In addition, verapamil is capable of causing foetal bradycardia, high-degree AV block and hypotension. Pregnancy is also related to an increased frequency of arrhythmias in previously asymptomatic patients with Wolff-Parkinson- White syndrome.35 Therefore, ajmaline 50–100mg IV over five minutes is an alternative antiarrhythmic drug in emergencies, particularly in patients with accessory pathways; this has been used for many years in non-pregnant patients with circus movement tachycardia.36 There are insufficient data regarding teratogenicity or other adverse effects to the foetus when ajmaline is used. Therefore, ajmalin should be avoided during the first trimester and used only when other therapeutic alternatives are not present or even unsuccessful. If vagal manoeuvres and/or unspecific or specific drugs are ineffective at terminating SVT, direct current (DC) cardioversion (10–50J) is well tolerated and effective at terminating the arrhythmia.4 In very few pregnant patients with otherwise untreatable tachycardia, either by drugs or by direct current energy, a ‘rescue’ radiofrequency ablation is indicated and possible, with excellent results and no serious side effects for the pregnant woman or the foetus.37
Atrial Fibrillation and Atrial Flutter
Any arrhythmia can occur in the pregnant woman and the frequency and symptomatic severity of arrhythmias may be increased during pregnancy. Although AF and AFlut are very frequent arrhythmias in adult non-pregnant patients, AF and AFlut are unusual in the absence of structural heart disease.5 Obviously, haemodynamic, hormonal, autonomic and emotional changes related to pregnancy may contribute. In the event of haemodynamic embarrassment caused by AF/AFlut with rapid ventricular response, electrical DC cardioversion is usually successful with 50–100J.38 Cardioversion should always be performed in a synchronised mode. In AF/AFlut with well tolerated haemodynamics, quinidine has the longest record of safety in pregnant woman for chemical cardioversion; however, other class Ia/Ic antiarrhythmia drugs are also safe for short-term use.10
Rate-slowing drugs (beta-blocking agents) should be administered before starting quinidine because of its vagolytic effect on the AV node. Rate control of AF is possible using digoxin, beta-blocking agents and/or verapamil. However, IV administration of verapamil carries a risk of precipitating maternal hypotension and secondary hypoperfusion, causing foetal bradycardia, high-degree AV block and hypotension.
Atrial Premature Beats
APBs in pregnant woman with structurally normal hearts are benign.10 APBs may become more frequent during pregnancy, or they may develop for the first time; many patients are worried about it.13 Patient education and reassurance is the first level of intervention of this benign condition. Exacerbating factors, such as chemical stimulants, should be identified and eliminated. Drug therapy is not needed in the vast majority of pregnant women. In patients who remain highly symptomatic, treatment with selective β-adrenergic-receptor-blocking agents should be considered. The few randomised studies of their use in pregnancy have yielded conflicting results regarding their effectiveness and safety. Beta-blocking agents readily cross the placenta and could, in large doses, cause a relative foetal bradycardia. The preferred drug for treatment of APBs is a β1-selective agent (metoprolol). In contrast, β2-blocking agents are associated in some cases with reduced utero–placental perfusion and/or foetal growth retardation, and should not be given.39
Acute Therapy of Ventricular Arrhythmias in the Pregnant Woman
One of the most important problems in intensive care, emergency medicine and cardiac rhythmology are pregnant patients with recurrent VT, ventricular flutter (VFlut) or VF. Management of cardiac arrest due to life-threatening ventricular tachyarrhythmias is essential to prevent sudden cardiac death in the mother and the foetus. However, treatment of the underlying arrhythmia requires a correct diagnosis. This is possible in the majority of patients using a 12-lead surface ECG.
Because a drug given for the treatment of SVT may be deleterious to a patient with VT, the differential diagnosis of a broad QRS tachycardia is critical. Wide-QRS-complex tachycardias (QRS duration >0.12s) often pose a difficult diagnostic and therapeutic problem.21 Errors are made because emergency care professionals wrongly consider VT unlikely if the patient is young and haemodynamically stable, and they are often unaware of the ECG findings that quickly and accurately distinguish VT in more than 90% of cases. To make the right diagnosis, a 12-lead ECG is ideal. Diagnostic clues for differentiation of VT from SVT are findings in lead V1 and V6; in addition, a QRS of 0.14s or more favours a diagnosis of VT. There are several possible mechanisms of wide-QRS-complex tachycardia.
Although sustained (duration >30s) VT is rare in pregnant women, there are some reports that VT (when occurring) originates in the patient with a normal heart mainly from the right ventricular outflow tract.21 Idiopathic left VT also occurs in pregnant patients with structurally normal hearts. In contrast to pregnant patients with normal left ventricular function, there is a poor prognosis when VT is associated with structural heart disease.10 For acute treatment, differentiation of VT – either haemodynamically unstable or stable – is essential. If at any time VT becomes unstable or there is evidence of foetal compromise, DC countershock (50–100J) should be delivered immediately (see Figure 1). If a DC shock of 50–100J is unsuccessful, higher energy is mandatory (100–360J); this carries no risk for mother or child. ‘Conservative’ therapy is indicated in any patient with sustained VT and stable haemodynamics (see Figure 2). Acute therapy should start with IV procainamide or with ajmaline 50–100mg IV over five minutes. Procainamide appears to be equally safe, is well tolerated and has no associated teratotoxicity, whereas the potential risk of ajmalin during pregnancy is unclear and its administration should be limited to emergencies.10
Another potential antiarrhythmic drug is lidocaine, which is not known to be teratogenic. Although several studies have shown some adverse effects (increase in myometrial tone, decrease of placental blood flow, foetal bradycardia), its use during the early stages of pregnancy is not associated with a significant increase in the incidence of foetal defects.4 Class III antiarrhythmic agents (sotalol, amiodarone) are very effective drugs in patients with ventricular tachyarrhythmias. During pregnancy, both drugs are of limited value: sotalol appears to be relatively safe, although there is a 3–5% risk of developing polymorphic or torsade de pointes tachycardia (see Figure 3). In addition, the β-adrenergic properties of sotalol must be considered. Amiodarone is well known for its many and serious side effects for both the mother and the foetus, including hypothyroidism, growth retardation and premature delivery.40,41 There is limited experience of amiodarone during pregnancy, and treatment with this drug should be reserved for life-threatening conditions.42 Magnesium is another drug with antiarrhythmic properties, particularly in patients with torsade de pointes tachycardia due to QT prolongation. It has been known for a long time that in emergencies, magnesium sulphate 1–2g IV delivered over one to two minutes is effective for treating and suppressing life-threatening ventricular tachyarrhythmias. Although this drug is associated with few side effects, maternal hypothermia and foetal bradyarrhythmias have been observed.43 In a few cases, verapamil is effective in pregnant women with right/left ventricular outflow tachycardia.44
Ventricular Fibrillation and Ventricular Flutter
Life-threatening VF or VFlut can occur at any stage of pregnancy and is associated with a high risk of sudden cardiac death. In patients with VF or VFlut, DC defibrillation is the treatment method of choice (100–360J). Prompt cardiopulmonary resuscitation and early defibrillation by either DC countershock or an automated external defibrillator significantly improve the likelihood of successful resuscitation from VF.45 For long-term therapy, the implantable cardioverter–defibrillator (ICD) is an excellent approach to terminate ventricular tachyarrhythmias and to prevent sudden death. There are few reports on ICD therapy during pregnancy, and these studies clearly show that ICD implantation did not negatively influence pregnancy, delivery or foetal health.46
Ventricular Premature Beats
Ventricular premature beats (VPBs) in pregnant woman with structurally normal hearts are benign and therapy is usually not necessary.10 Patient education and reassurance are the first level of intervention for this benign condition. Exacerbating factors, such as chemical stimulants, should be identified and eliminated. In patients who remain highly symptomatic after all steps have been taken, treatment with selective β-adrenergic-receptor-blocking agents is indicated. The few randomised studies of their use in pregnancy have yielded conflicting results regarding their effectiveness and safety. Beta-blocking agents readily cross the placenta and could, in large doses, cause a relative foetal bradycardia. Preferred drugs for treatment of VPBs are β1-selective agents such as metoprolol. In contrast, β2-blocking agents are associated in some cases with reduced utero–placental perfusion and/or foetal growth retardation, and should not be chosen for treating VPBs.39 There is no indication for treatment with class III antiarrhythmic drugs due to their side effects and the associated risk of proarrhythmia.14
Acute Therapy of Foetal Arrhythmias
Management of foetal arrhythmias is very difficult and requires co-operation between different consultants (obstetrics, cardiology, neonatology). The problem of foetal tachyarrhythmias is the risk of hydrops fetalis and subsequent death.47 SVTs are the most common foetal tachycardias, whereas other arrhythmias are observed less frequently. An analysis of 11 studies reported from 1991 to 2002 showed a foetal SVT as the underlying arrhythmia in 73.2% and AFlut in 26.2%.48 The incidence of hydrops fetalis was similar in those with AFlut or SVT (38.6 versus 40.5%; p=NS). Intrauterine death was 8.0% in foetal AFlut and 8.9% in foetal SVT (p=NS).
The treatment of foetal arrhythmias is possible by either treating the mother or treating the foetus directly. Antiarrhythmic agents that have been used to treat foetal arrhythmias include digoxin, beta-blocking agents, verapamil, procainamide and quinidine. In addition, in cases of foetal ventricular tachyarrhythmias, class I and class III antiarrhythmic agents have been advocated.6,13 Recently, Anderer et al. reported a 25- year-old pregnant woman with persistent foetal tachycardia (rate 267bpm) and subsequent hydrops fetalis.47
The woman was treated with flecainide and digoxin and tachycardia converted to sinus rhythm. A few days later, no signs of foetal heart failure were present. In another publication, Khosithseth et al. described three cases with hydrops fetalis due to supraventricular tachyarrhythmias successfully treated with amiodarone and digoxin or the combination of digoxin, procainamide and propranolol.40
Direct Foetal Therapy
If maternal therapy fails to suppress or sufficiently decrease the rate of foetal tachyarrhythmias, direct drug administration to the foetus is mandatory. Direct foetal treatment regimes have been used that consist of intraperitoneal and/or umbilical IV administrations of different drugs. In addition, umbilical drug administration allows not only direct treatment but also drug monitoring. Hansmann et al. described 60 cases with foetal arrhythmias: 26 cases (43%) with hydrops fetalis and 34 cases without (57%). When tachyarrhythmias were refractory to transplacental treatment, foetal therapy was performed with direct umbilical drug administration.49 Of those 60 cases, 54 were SVT and six were AFlut. During the nine years of the study, different drug regimes had been used. Twenty foetuses (77%) with tachyarrhythmias and hydrops fetalis survived and all 34 non-hydropic foetuses survived. Therefore, direct foetal therapy is highly effective in SVT and AFlut and will lead to foetal survival. Amiodarone seems to be the drug of choice for direct therapy; however, there are also other effective drugs (digoxin, beta-blocking agents, flecainide, adenosin).50,51 Despite the many side effects of amiodarone, the majority of children in the perinatal period are completely normal despite intrauterine therapy with amiodarone for tachyarrhythmias.
During pregnany an increased incidence of maternal cardiac arrhythmias is observed, ranging from clinically irrelevant isolated APBs or VPBs to debilitating SVT and VT or VF. In all pregnant patients with tachyarrhythmias, evaluation of the underlying aetiology and the degree of left ventricular function/dysfunction is essential. Correct treatment of arrhythmias in the intensive care patient should be based on understanding the causal mechanism. In pregnant women with maternal and/or foetal arrhythmias, therapeutic strategies should be based on interdisciplinary co-operation (obstetrics, cardiology, neonatology). In general, acute therapy of arrhythmias during pregnancy is similar to that in the non-pregnant patient. However, special consideration should be given to potential teratogenic and haemodynamic adverse effects on the foetus. With this in mind, a successful pregnancy, for both mother and foetus, can usually be the result.