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Arch Gynecol Obstet (2004) 269:244253DOI 10.1007/s00404-002-0461-x

Abstract Introduction: An increased incidence of ma-ternal cardiac arrhythmias is observed during pregnancyand they can range from clinically irrelevant isolated

premature beats to debilitating supraventricular and ven-tricular tachycardias. Discussion: Management of ar-rhythmias during pregnancy is similar to that in non-pregnant patients. However, the presence of the foetusand the risk of teratogenicity, the haemodynamic chang-es, the effect of therapy on labour, delivery and lactationmust be evaluated. Antiarrhythmic drug selection de-pends on the specific arrhythmia being treated and thecardiac condition of the mother. Although no drug iscompletely safe, most are well tolerated and can be givenwith relatively low risk. Some antiarrhythmic agents,such as propranolol, metoprolol, digoxin and quinidine,have been extensively tested during pregnancy and haveproved to be safe; they should therefore, whenever possi-ble, be used as a first-line. For supraventricular tachycar-dia, intravenous adenosine may be used to terminate thearrhythmia if vagal manoeuvres fail. If possible, drugtherapy should be avoided during the first trimester ofpregnancy. When drug treatment fails or is not indicatedbecause of the haemodynamic instability of the patient,direct current cardioversion can be used. Conclusion:Most patients with arrhythmias during pregnancy can betreated with an excellent result.

Keywords Arrhythmias Antiarrhythmic drugs Pregnancy

Introduction

Normal physiologic changes, which occur during gesta-tion, can aggravate underlying cardiac disease and lead tothe associated morbidity and mortality. Maternal adapta-tion to pregnancy includes plasma volume changes withan increase in total body water, vascular alteration with adecrease in systemic resistance and modifications associ-ated with hypercoagulability. These explain, in part, theappearance of signs and symptoms, even in a normalpregnant woman, that are difficult to distinguish fromthose occurring in heart disease and why some cardiacabnormalities are not well tolerated during pregnancy.

An increased incidence of maternal cardiac arrhyth-mias is observed during pregnancy but life-threateningrhythm disorders are relatively rare. The foetus may suf-fer both haemodynamic alterations and adverse effects ofthe treatment. Teratogenic risks are higher during orga-nogenesis in the first 8 weeks of pregnancy, after this pe-riod this risk is greatly reduced but drugs may affect foe-tal growth and development. Moreover, most cardiolo-gists do not have extensive experience in treating thesekinds of patients and the knowledge that therapy may af-fect the foetus is sometimes intimidating.

Arrhythmias during pregnancy include a wide spec-trum: the most common are simple ventricular and atrialectopy (reported in 50 to 60% of pregnant women) [77]but also sinusal tachycardia in the gestation period is acommon find. Supraventricular tachycardia (SVT) oc-curs more frequently during pregnancy. Others supraven-tricular arrhythmias can occur especially in pregnantwomen with congenital heart disease, ischaemic cardiop-athy, cardiomyopathy, valvulopathy (such as prolapse ofmitral valve).

In this report we review the management of arrhyth-mias during pregnancy showing that most patients can betreated with an excellent result.

S. Ferrero () N. Ragni

Dipartimento di Ostetricia e Ginecologia,Universit degli Studi di Genova,Padiglione 1 Ospedale San Martino, Largo Rosanna Benzi 16132,Genova, Italye-mail: simoneferrero@libero.itTel.: +39-010-511525, Fax: +39-010-511525

S. FerreroDepartment of Obstetrics and Gynaecology,St. Bartholomews Hospital, West Smithfield, London, UK

B. M. ColomboDipartimento di Medicina Interna,Universit degli Studi di Genova,Ospedale San Martino, Largo Rosanna Benzi 16132, Genova, Italy

O R I G I N A L A R T I C L E

Simone Ferrero Barbara Maria ColomboNicola Ragni

Maternal arrhythmias during pregnancy

Received: 22 February 2002 / Accepted: 10 July 2002 / Published online: 16 January 2003 Springer-Verlag 2003

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cardia is haemodynamically well tolerated, but directcurrent (DC) cardioversion should be performed if drugtreatment fails. Direct current cardioversion restores si-nus rhythm for forms of sustained tachycardia, which arehaemodynamically not well tolerated by pregnant wom-an and that cause foetal hypoperfusion. Direct currentcardioversion is safe at all stages of pregnancy [24, 46,

62, 73] and the risk of inducing foetal arrhythmias issmall, because the current reaching the foetus is insignif-icant. However is necessary monitor foetal rhythm, be-cause transient foetal arrhythmia has been reported dur-ing DC cardioversion of pregnant woman.

Antiarrhythmic agents

Quinidine (class IA, category C)

Quinidine has been used during pregnancy since the1930s. Although pregnancy-related adverse effects asso-ciated with quinidine are uncommon [21, 22, 41, 57, 58],some have been reported. It has been reported that quini-dine can induce mild uterine contractions [58], prema-ture labour [5] and neonatal thrombocytopenia [55]. Attoxic doses, quinidine has been reported to cause miscar-riage [88] or possibly cranial nerve VIII injury [57]. Ingeneral, quinidine is considered safe during pregnancyand it is probably the class IA drug of choice. Quinidinelevels in breast milk are lower (70%) than in serum.

Procainamide (class IA, category C)

Procainamide has been used frequently and no evidenceof teratogenicity has been reported even when used dur-ing the first trimester of pregnancy [2, 24, 40]. Its chron-ic use may be associated with a lupus-like syndrome, asin non-pregnant patients [24]. Probably, procainamide

levels in breast milk are clinically insignificant [24],however the experience with its use in pregnancy andlactation is too limited to grant any recommendation re-garding its use.

Disopyramide (class IA, category C)

Even if reported experience with disopyramide duringpregnancy has not been associated with teratogenicity[24], the experience is limited and caution is warranted.Disopyramide can cause uterine contractions [51].

Lidocaine (class IB, category B)

Despite significant placental drug transfer [11], lidocaineis not known to increase the risk of foetal malformations[40]. However, it increases myometrial tone [38], de-creases placental blood flow [78] and causes foetal bra-dycardia [53]. Its administration during foetal acidosiscan cause heart and central nervous system toxicity inthe newborn [13]. Lidocaine is excreted in breast milk,but the amount ingested by the infant is very small andshould not pose a hazard [24].

Table 1 Food and Drug Administration Pregnancy Risk Classification (abbreviated) (Page 1995)

Category Risk

A Controlled studies show no risk B No evidence of risk in pregnant women. Either animal studies show risk but human studies do not, or animal studies

do not show risk but no adequate studies in humans have been conductedC Studies in pregnant women are lacking, and animal studies are either positive for foetal risk or lacking as wellD Positive evidence of risk. Investigational or post-marketing data show risk to the foetus, but the benefit from use

in pregnant women may be acceptable despite the risk

X Positive evidence of risk. Investigational or post-marketing data show risk to the foetus and the risk of use of thedrug in pregnant women clearly outweighs any possible benefits. The drug is contraindicated on women who areor may become pregnant

Table 2 Classification of antiarrhythmic drugs (Vaughan Williams 1984)

Class Type Name

I Sodium channel blocking agentsIA Drugs that prolong the action potential duration Quinidine, procainamide, disopyramideIB Drugs that cause shortening of the action potential duration Lidocaine, mexiletine, phenytoinIC Drugs with little effect on action potential duration but that Flecainide, propafenone

cause profound slowing of conductionII adrenergic blocking agents Propranolol, metoprolol

III Potassium channel blocking agents Sotalol, amiodarone, ibutilideIV Calcium channel blocking agents Verapamil, diltiazemOther Digoxin, adenosine

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QT interval, prematurity, miscarriage and death [89].Amiodarone must be used only in life-threateningarrhythmias resistant to other drugs [89]. Amiodaroneappears at a higher level in breast milk than in maternalserum: a nursing infant may be exposed to the equivalentof a low adult maintenance dose [56]. Even if adverse ef-fects on nursing infants have not yet been proven, it isrecommended that patients on amiodarone therapy are

not currently or have within the past few months been,breast-feeding.

Calcium antagonists (category C)

Calcium antagonists have been widely used in the treat-ment of foetal supraventricular tachycardia [91], in theprevention of preterm delivery [83] and pre-eclampsia[74].

Verapamil is the preferred calcium antagonist to pre-scribe during pregnancy. Verapamil is used for acute andchronic treatment of supraventricular tachycardia, both

in the mother [90] and foetus [32, 91]. No evidence ofteratogenicity or severe adverse effects has been reportedwith the use of verapamil during pregnancy [4, 24, 83].However, maternal and/or foetal hypotension, bradycar-dia, atrioventricular block and contractility reductionhave been described during the treatment of foetal ar-rhythmias [62]. Intravenous administration of verapamilcarries a risk of maternal hypotension and blood uterineflow reduction. Because of these reasons adenosine, ifdisposable, must be preferred to verapamil.

Knowledge about the use of diltiazem during preg-nancy is limited. Some animal studies suggest that, invery large doses, it may cause skeletal abnormalities, de-

creased foetal weight and even foetal death [18, 24]. Itmay also inhibit uterine contractions and delay delivery.One retrospective analysis of 27 newborns exposed dur-ing the first trimester to diltiazem suggests an associa-tion with birth defects [10].

There is limited data regarding the safety of calciumantagonists during lactation. Verapamil is excreted inbreast milk, with reported concentrations varying be-tween 23% and 94% of those in maternal serum [24].

Digoxin (category C)

Digoxin has been widely used during pregnancy in thetreatment of foetal and maternal arrhythmias [24, 30]and it can be considered the most secure anti arrhythmicdrug in pregnant woman on therapeutic doses. It is con-sidered a preferred choice for acute and chronic treat-ment of supraventricular tachycardias in the mother andfoetus [19, 32, 84], including atrial fibrillation, atrialflutter, and atrial tachycardias. Digoxin crosses the pla-centa freely and its serum levels are similar in the moth-er and newborn [69]. Digitalis toxicity during pregnancyhas been associated with miscarriage and foetal death,probably due to maternal cardiac instability, uterine hy-

poperfusion and foetal anoxia [65, 75]. Serum digoxinlevels may decrease by 50% during pregnancy due to in-creased renal excretion [48]. This decrease is not likelyto be an artefact of reduced serum protein concentration,because digoxin is not highly protein-bound [68]. Main-tenance doses may require reduction in the presence ofdecreased renal function or co-administration of quini-dine, verapamil or amiodarone. Digoxin plasma levels

during the third trimester of pregnancy may be difficultto evaluate, because some substances that interfere withthe radioimmunoassay are present in the blood of themother [59]. Because of this, a therapeutic dose can beassociated with toxic plasma level. On the contrary, in-creased renal excretion during pregnancy can be associ-ated with a reduction of the plasma level of the drug.

In women with therapeutic blood levels, digoxin ex-cretion in the milk is less than 2 g/die, but this amountis not dangerous for the baby [6]. After delivery, digoxinrequirements may be decreased from the pregnant stateas pharmacokinetic parameters normalize.

Adenosine (category C)

Some authors advocate adenosine as the first choicetreatment of SVT during pregnancy [38, 54] because itis an endogenous nucleoside, it has rapid action, its half-life is very short (

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Non-pharmacological treatment

The vagal manoeuvres (carotid sinus massage, Valsalvamanoeuvre, diving-reflex) are well tolerated during preg-nancy and they must be the first treatment of tachycar-dias, both with normal and large QRS. Performing ECGduring these manoeuvres may help in diagnosis [66].

Emergency and elective DC cardioversion is safe dur-

ing all phases of pregnancy [24, 46, 62]. Little electricalcurrent actually penetrates the uterus and the threshold toprovoke arrhythmias is higher in the foetal heart [24,62]. Anyhow, it is preferable to perform the procedurewith foetal rhythm monitoring, because transient foetalarrhythmias have been reported.

It was shown that pregnancy in patients with an im-plantable cardioverter-defibrillator does not cause com-plications or adverse events in the mother or foetus [61].Thus, it was suggested that pregnancy should not be dis-couraged merely because an implantable cardioverter-de-fibrillator is present.

Use of pacemakers, permanent or temporary, is neces-

sary to alleviate symptoms caused by bradycardia or toprevent severe symptoms in women who are likely to de-velop symptomatic bradycardia. In the first trimester ofpregnancy the implantation of a pacemaker may be te-ratogenic but it is possible to decrease the risks related toradiation exposition with a protective device. In somecases, during the last trimester of pregnancy, a temporarypacemaker can be used in emergency conditions beforecaesarean section.

Radio frequency catheter ablation is a percutaneouscatheter technique that can eliminate a variety of supra-ventricular and ventricular arrhythmias. In patients withfrequent atrioventricular nodal re-entrant tachycardia,

atrioventricular reciprocating tachycardia episode, atrialflutter and idiopathic ventricular tachycardia, RF abla-tion prior to pregnancy should be considered (obviously,RF ablation during pregnancy is highly undesirable be-cause of the need for fluoroscopy). RF ablation for atrialfibrillation has recently been reported in a patient inwhom this arrhythmia is induced by atrial tachycardiaepisodes originating in or near the ostia of the pulmonaryveins [39].

There is not sufficient data about transcutaneous car-diac stimulation during pregnancy.

Management of specific maternal arrhythmias duringpregnancy

Some general guidelines in managing arrhythmias duringpregnancy may be formulated.

Cardiac arrest

Cardiac arrest is a rare occurrence in pregnant women.Its treatment involves special consideration especially inthe late stages of pregnancy. Standard cardiopulmonary

resuscitation (CPR), with the patient in the traditional su-pine position, may fail, especially in the last trimester ofpregnancy. The gravid uterus acts like an abdominalbinding, increasing intra-thoracic pressure and reducingboth venous return and aortic flow [43, 46]. Successfulresuscitation may be obtained performing standard CPRwith the pregnant woman in a particular position: the pa-tient is tilted on her side using either a wedge or another

rescuers knees for support [35]. Standard CPR protocolmust be followed because there is literature documentingsuccessful cardioversion with no adverse effect on themother or foetus discharging at 300 J. Emergency cae-sarean section can make the resuscitation of the mothereasier [3].

Ventricular tachycardia

Ventricular tachycardia (VT) is uncommon in youngwomen, but its incidence may increase during pregnancyand its symptoms may be severe [9, 12]. Ventricular

tachycardia may arise in young pregnant women withstructurally normal hearts, but these patients are at lowrisk for subsequent mortality and morbidity. Ventriculartachycardia may also be seen in patients with acquired orcongenital abnormalities and may have a more seriousprognosis than idiopathic VT. Women with hypertrophiccardiomyopathy, right ventricular dysplasia, peripartumcardiomyopathy and coronary artery disease have in-creased risk of recurrent-paroxysmal VT.

Ventricular tachycardia can be haemodynamically un-stable or stable. If it is stable and therapy is necessary, -blockers are the drug of choice [49]. Caution not to in-duce maternal hypotension and subsequent foetal hypo-

perfusion is advised when administering these drugs.When VT is unstable, immediate DC cardioversion isappropriate and, in this case, lidocaine is the drug ofchoice. Chronic antiarrhythmic therapy may be unavoid-able in the face of sustained or recurrent VT: the drugs ofCategory C (quinidine, procainamide, flecainide) and so-talol are the drugs of choice [11].

Supraventricular tachycardia

Supraventricular tachycardias, in which the atrioventric-ular node is part of the re-entry circuit, include atrioven-tricular nodal re-entrant tachycardia and atrioventricularreciprocating tachycardia involving an accessory path-way, as in WPW syndrome. Also in these cases all anti-arrhythmic drugs should be considered potentially toxicto the foetus and, if is possible, non-pharmacologic orpreventive measures should be taken. Sustained tachy-cardia in both forms may be terminated by vagal ma-noeuvres, which transiently block atrioventricular nodalconduction. If these measures fail, drug therapy is need-ed, especially if haemodynamic instability and the symp-toms are not bearable or there is a threat for the foetus orpregnant woman. Intravenous adenosine is effective in

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terminating re-entrant tachycardias that involve AV nodeas a part of their re-entrant circuit (Fig. 1) [16]. If long-term therapy is needed, verapamil, digoxin and -block-ers may be used. In atrioventricular reciprocating tachy-cardia with an accessory pathway, class I antiarrhythmicdrugs (procainamide and quinidine) may be used toblocking accessory pathway conduction. In patients withan accessory pathway who have atrial fibrillation, the

therapy should not be aimed at suppression of atrioven-tricular nodal conduction, because this may facilitateconduction over the accessory pathway, thereby raisingthe ventricular rate. In these patients effective drugs areprocainamide or quinidine (class I), which slow accesso-ry pathway conduction and may prevent or terminateatrial fibrillation. Patients with frequent atrioventricularnodal re-entrant tachycardia or atrioventricular recipro-cating tachycardia episodes need RF ablation prior topregnancy. In some cases electrical cardioversion is nec-essary: 1050 J of energy is usually sufficient.

Atrial flutter and atrial fibrillation

These rhythms are rare in women of childbearing age andthey are usually associated with structural heart disease.If an obvious provoking factor is present (alcohol abuse,thyroid dysfunction), the treatment should be aimed atthis factor. If spontaneous cardioversion to sinus rhythmdoes not occur, early cardioversion should be performedto avoid the need of anticoagulation. Quinidine is theagent of choice for chemical cardioversion of atrial fibril-lation and flutter. Procainamide is also safe for short termuse. There is no reported data on ibutilide use duringpregnancy. When cardioversion is impossible, adequate

rate control must be achieved to prevent haemodynamiccompromise of placental blood supply (ideally

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paroxysmal supraventricular tachycardias. These womenmay have atrioventricular reciprocating tachycardiatreated as other SVT. Episodes of atrial fibrillation mayoccur in patients with WPW syndrome, in which caseventricular frequency increases and causes ventricular fi-brillation. Procainamide is the drug of choice in womenpresenting wide complex tachycardia, if it is of uncertainorigin and is haemodynamically stable. Cardioversion is

indicated in all unstable patients. Radio frequency abla-tion should be considered in all patients with WPW syn-drome before attempting pregnancy.

Supraventricular and ventricular ectopic beats

Ventricular or supraventricular ectopy in structurallynormal hearts has no clinical significance. The primarygoal in its management is reassurance. Exacerbating fac-tors, such as chemical stimulating agents (caffeine,smoking and alcohol) should be identified and eliminat-ed. Drug therapy is not needed in the vast majority of

cases. If ectopy continues despite these measures and itis very bothersome, -blockers may be used. Propranololis very effective in reducing the frequency of palpitationsand alleviating anxiety. Metoprolol may be a better alter-native in bronchospastic patients and its 1 selectivitymay confer additional benefits in terms of its safety pro-file.

Bradyarrhythmias

Sinusal bradycardia is uncommon in pregnancy and it canbe associated with orthostatic hypotension; the enlarged

uterus compresses the inferior cava vein and it can makethis condition worse decreasing venous return. Vasovagalsyncope is one of the most common causes of symptomat-ic bradycardia in women of childbearing age but it is rareduring pregnancy. In the case of congenital or acquiredcardiac bloc, in symptomatic pregnant women the therapyof choice is an implantable pacemaker. In asymptomaticpregnant women, Valsalvas manoeuvre during deliverycauses decrease in cardiac frequency and may lead to syn-cope or convulsion. In this case a temporary pacemaker isnecessary to sustain woman during delivery [25].

Intrapartum management

Labour and delivery are associated with significanthaemodynamic changes, as well as with pain and anxi-ety, all of which could enhance arrhythmias. Pregnantwomen with arrhythmias should undergo caesarean sec-tion only for obstetrics indications. A caesarean may beappropriate in the case when the blood pressure fluctua-tions associated with labour are contraindicated and can-not be controlled. Continuous cardiac monitoring may benecessary intrapartum and postpartum for symptomaticor complex arrhythmias.

Conclusion

Almost all kinds of ventricular and supraventricular ar-rhythmias can occur during pregnancy. Medical caremust be initiated early, sometimes prior to conception,but therapy should be provided only when the arrhyth-mias cause severe symptoms or haemodynamic compro-mise. Many factors must be evaluated in the administra-

tion of antiarrhythmic drugs: the presence of the foetusand the risk of teratogenicity, the haemodynamic chang-es, the effect of therapy on labour, delivery and lactation.

In general, arrhythmias during pregnancy can be safe-ly managed and many of the currently available antiar-rhythmic drugs are safe for the foetus. If possible, drugtherapy should be avoided during the first trimester ofpregnancy, because teratogenic risks are higher duringorganogenesis. Drugs with the longest record of safe usein pregnancy should be used as first-line therapy; the cli-nician must use the least number of medications possibleand prescribe the lowest dose of drugs that is effective.Drugs should be administered with close and frequent

monitoring.When drug treatment fails or is not indicated because

of the haemodynamic instability of the patient, DC car-dioversion can be used. Emergency and elective DC car-dioversion has been proved to be safe during all phasesof pregnancy.

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