REVIEW

Heart Disease and Pregnancy

Reza Ashrafi . Stephanie L. Curtis

Received: February 22, 2017 / Published online: July 5, 2017� The Author(s) 2017. This article is an open access publication

ABSTRACT

Cardiac disease remains a major cause of mor-bidity and mortality in pregnant and post-par-tum women, although progress has been made,with specialist joint obstetric–cardiology clinicsproviding an integrated, safe and personalisedservice to these women. As a result, fewernon-specialist cardiologists are managingwomen in pregnancy with cardiovascular dis-ease. The aim of this review is to provide a briefoverview of current knowledge and practice inthe field, with an emphasis on the major phys-iological changes which occur during preg-nancy, focussing on progress through thetrimesters, clinical assessment in pregnancy,management of delivery (concentrating onmanaged vaginal delivery), drug treatment, keyconditions and risk assessment. The latter factoris particularly important in terms of being ableto identify high-risk women earlier and tocounsel them appropriately. Pregnant womenwith cardiovascular conditions can, withappropriate knowledge and counselling, be

managed safely in specialist multidisciplinaryservices, but there is a need for cardiologists tounderstand the key changes and risks involvedin pregnancy, delivery and the post-partumperiod.

Keywords: Pregnancy; Heart disease; Gender

INTRODUCTION

With improved maternal medical care and fer-tility treatments, an increasing proportion ofwomen with congenital cardiac disease andacquired heart disease are becoming pregnantand delivering safely [1]. However, pregnancyhas a profound effect on the cardiovascularsystem, and many conditions are associatedwith a significant risk of foetal and maternalmorbidity and mortality.

It has been reported that 0.2–0.4% of allpregnancies are complicated by cardiovasculardisease [2], and although death is rare, cardio-vascular disease is the biggest indirect cause ofmaternal death worldwide, with anattributable rate of two deaths per 100,000 [3] inthe UK and a similar rate in other countries[4, 5]. The epidemiology of cardiovascular dis-ease in pregnancy varies significantly depend-ing the location of the mother, with muchvariation in disease rates and processes. World-wide, hypertensive disease in pregnancy is by

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R. Ashrafi (&) � S. L. CurtisCongenital Cardiac Centre, Bristol Heart Institute,Bristol Royal Infirmary, Marlborough Street, Bristol,UKe-mail: rezaashrafi@riseup.net

Cardiol Ther (2017) 6:157–173

DOI 10.1007/s40119-017-0096-4

far the most prevalent cardiovascular disorder,complicating 2–8% of all pregnancies in theWestern world, predominantly in Latin Americaand the Caribbean, where it causes one-quarterof all maternal deaths [6]. Rheumatic heartdisease is common in developing countries butare now rare in the Western world [7]. A similarvariation is observed in peripartum cardiomy-opathy (PPCM), with a rising incidence inWestern society, estimated most recently at1:2229 [8], but an estimated rate of 1:1000 inAfrica and 1:300 in Haiti [6]. An exact preva-lence of women with congenital cardiac disor-ders who are pregnant is difficult to estimatelargely due to the methodology involved in thereported studies, but in the USA nine per 10,000delivery hospitalisations were for women withcongenital heart disease [9].

In most Western countries, most womenseen in cardiac–obstetric services have congen-ital heart disease. Death is rare, but when it doesoccur it is most often due to myocardialinfarction (often coronary dissection), ascend-ing aortic dissection, cardiomyopathy and sud-den adult cardiac death [10].

The first area addressed in this review is thephysiology of the cardiovascular system duringpregnancy. In this section we focus on the keychanges that cardiologists need to be aware of.

This article does not contain any new studieswith human or animal subjects performed byany of the authors.

Physiological Changes in Pregnancy

Pregnancy has a dramatic effect on the cardio-vascular system, and the effects are sustainedinto the post-partum period.

Before there is even placentation, there issystemic vasodilatation at around 5 weeks ges-tation. Systemic vascular resistance (SVR) isprogressively reduced (by 35–40%) until themiddle of the second trimester, when it plateausbefore beginning to increase late in the thirdtrimester [11]. This variation is associated with adrop in mean arterial blood pressure in the firsttwo trimesters prior to its recovery in the thirdtrimester to close to pre-pregnancy levels. Thechanges in SVR are thought to be due to the

vasodilatory properties of oestrogen, proges-terone and relaxin, which are all increasedduring pregnancy, and to reduced vasopressorreceptor sensitivity. In addition, there alsoappears to be an increased amount of vascularnitric oxide production which contributes tothe vasodilatation and reduced SVR [12].

Structurally there is a progressive increase inleft ventricular end-diastolic volume and mass[11, 13] into the third trimester, but there is asharp drop in left ventricular mass late in thethird trimester [13]. From the first trimesteronwards, there is an increase in maternal heartrate which continues throughout pregnancy[14] and is on average 30 beats per minutehigher than the baseline maternal heart rate bythe end of the pregnancy. These adaptations arelikely to be required to cope with the extra cir-culating blood volume, which has increased byan average of 40%, reaching a maximum valueat 24 weeks.

As expected, given the physiologicaldemands of the utero-placental circulation andthe developing foetus, there is an increase incardiac output, with the biggest increase of upto 45% from baseline occurring during the firsttrimester [15, 16]. The increase in cardiac out-put slows late in the second trimester and dropsslightly late in the third trimester [11] (but stillstays above pre-pregnancy levels). Table 1 sum-marises the main cardiovascular physiologychanges during pregnancy by trimeste, andFig. 1 summarises the main cardiovascularphysiology changes during pregnancy by tri-mester and percentage change.

It should be noted that these haemodynamicchanges most often regress to pre-pregnancylevels, but some studies have suggested that thechanges in left ventricular mass and vascularresistance do not fully return to pre-pregnancylevels.

As well as the circulatory changes describedabove, there are also adaptive changes thatoccur in the great vessels and blood that areimportant to women with heart disease.Expression of oestrogen receptors in the aortacauses fragmentation of reticulin fibres, reducedamount of acid mucopolysaccharides and lossof the normal arrangement of elastin fibers,

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predisposing women to aortic dissection, par-ticularly if they have an aortopathy [17]. Addi-tionally, pregnancy is a hypercoagulable state,designed to reduce the risk of post-partumhaemorrhage [18]. This results in an increasedrisk of clotting, most commonly venousthromboembolism, but women who requireanticoagulation for heart disease are atincreased risk. For those with mechanical heartvalves, pregnancy is a high-risk undertaking.

PRE-CONCEPTION MANAGEMENT

In this section we discuss those aspects of car-diac–pregnancy management which most

physicians feel to be of the greatest importance,and the identification of women at risk andtheir pre-pregnancy counselling of their ownindividual risk involved in pregnancy anddelivery.

Pre-pregnancy Counselling and RiskAssessment

The most important aspect of assessment ofreproductive-age women with cardiac disease ispre-conception counselling. Any assessmentneeds to cover the risks of pregnancy to themother and foetus. Risks to the mother includewhether she can tolerate the expected

Table 1 Summary of the key cardiovascular physiological changes which occur during pregnancy

Variable First trimester Second trimester Third trimester Early post-partum

SVR ; ; ;–with a late rise :

Heart rate : : : ;

LVEDD : : : ;

LV mass : : :–with a late drop ;

Cardiac output : : :–with a late drop ;

LV longitudinal strain No change No change ; :

LV Left ventricular, LVEDD LV end diastolic diameter, SVR systemic vascular resistance

Fig. 1 Summary of the cardiovascular physiologicalchanges in pregnancy by percentage change and trimester.HR Heart rate, MAP mean arterial blood pressure, SVR

systemic vascular resistance, CO carbon dioxide, LV leftventricular, T1, T2, T3, trimester 1, 2, 3, respectively

Cardiol Ther (2017) 6:157–173 159

haemodynamic changes that occur in preg-nancy, the need for highly medicalised ante-natal care and delivery, possibly a prematuredelivery, that may be far from home and thelong-term effects on the heart condition of apregnancy. In the case of cardiomyopathies [19]and systemic right ventricles [20], there is evi-dence that pregnancy can have a deleteriouslong-term effect on ventricular function. Inwomen with complex cardiovascular disordersthat adversely affect their life expectancy, frankdiscussions need to be had about the long-termcommitment of parenting and the importanceof family or other social support.

Cardiopulmonary exercise testing can beuseful in estimating the likelihood of compli-cations [2]. Drugs that are contraindicated inpregnancy need to be stopped, and if cardiacfunction is dependent on these drugs, such asangiotensin-converting enzyme inhibitors inleft ventricular dysfunction, it is important toassess the woman again when they have beendrug free for several months to ensure thatventricular function does not deteriorate.

Assisted reproduction involves a wide rangeof techniques and medications, some of whichcan be invasive and lead to significant cardiacstrain, with some evidence of increased com-plications compared to unassisted reproduction[21]. These risks should be discussed, not onlywith the patient before she embarks on anyassisted reproduction programme but also withthe cardiology team looking after the patient soas to best manage the risks. As multiple foetusesare a more common occurrence in assisted fer-tility programmes, the extra haemodynamicstress and likelihood of premature delivery/in-creased rates of hypertension also need to bediscussed with the patient before she starts theprogramme [22].

Risks to the foetus that need to be discussedare the effects of drugs that may need to becontinued and the possibility of miscarriage,prematurity, intra-uterine growth restrictionand low birth weight and its implications.Detailed pre-conception counselling is espe-cially important in the case of anticoagulation

(this aspect will be discussed in more detailfurther in the text).

It is also important to consider the likelihoodof recurrence of the disease in the case ofinherited cardiac conditions and congenitalheart disease. In autosomal dominant condi-tions, such as Marfan syndrome, many patientsare aware of the inheritance risk as familymembers are commonly affected. However,many patients are unaware of the inheritancerisk of congenital heart disease and oftenassume it to be higher than it is. Recurrence riskvaries from 0 to 20%, depending on the lesion.The most heritable lesions are left-sidedobstructive conditions, such as bicuspid aorticvalve disease and coarctation, and the leastheritable are the transposition complexes[21–26].

There is some evidence that pre-conceptionmultivitamins and folic acid supplementationreduces the risk of heritable congenital heartdisease in the foetus [23, 24].

Risk Assessment for IndividualCardiovascular Disorders

Assessment of maternal risk prior to conceptionhas been studied by several groups and refinedin risk assessment scores, such as CARPREG [25]and ZAHARA [26], which are summarised inTable 2. Factors that increase the risk of mater-nal cardiac events include left heart obstructivelesions (aortic or mitral stenosis), cardiacsymptoms, cyanosis, systemic ventricularimpairment and previous cardiac events. Atri-oventricular valve regurgitation (mitral or tri-cuspid) also confers an increased risk. However,the most high-risk situation is the presence of amechanical valve and the associated risk of fullanticoagulation.

The current European Society of Cardiologyguidelines suggest using the modified WorldHealth Organisation (WHO) system [27] whenassessing women prior to pregnancy, and thisforms the basis for the small number of condi-tions that are thought to be a contraindicationto pregnancy (shown in Table 3).

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PREGNANCY AND PRE-DELIVERY

After the key phase of pre-assessment, and carefocusses on the assessment during pregnancyand the management of specific conditions.

Clinical Assessment and InvestigationsDuring Pregnancy

Cardiac assessment of the pregnant patient canbe difficult as common symptoms of pregnancy,such as breathlessness and fatigue, can mimiccardiac symptoms. Also, clinical signs, such asmild dependent oedema, a minimally raisedjugular venous pressure, collapsing pulses andan ejection systolic murmur, are common inpregnancy and can result in difficult assess-ments [28]. Signs and symptoms which areabnormal in pregnancy include extremebreathlessness, marked oedema, a fourth heartsound, diastolic murmurs, jugular venous pres-sure of [2 cm and a persistent tachycardia of[100 beats per minute; any one of these shouldprompt further evaluation [29].

Electrocardiography (ECG) is a common anduseful diagnostic tool throughout pregnancy forcomplaints such as chest pain/arrhythmias.Subtle changes in the ECG are common in laterpregnancy and include left axis deviation,inverted T waves and inferior Q waves due todiaphragmatic elevation [30]. Chest radiogra-phy is a safe investigation modality in preg-nancy and should be performed readily asrequired [31].

After the ECG, the most common investiga-tion that most cardiologists will utilise is theechocardiogram, which is based on ultrasoundand therefore safe throughout the pregnancy.As would be predicted from the changes inmaternal physiology, there is an observableincrease in left ventricular diameter measure-ments on echocardiography, such as the leftventricular end diastolic and systolic dimen-sions [32]. Assessment of ventricular function ismade utilising identical techniques to thoseused in the non-pregnant women, with ejectionfraction, tissue Doppler and m-mode measure-ments all useful in serial monitoring. Therehave been some inconsistencies in the reporting

Table 2 CARPREG and ZAHARA scoring systems for estimating the risk of a cardiac complication during pregnancy

Risk factor in CARPREG scoring (1 point for each factor) Total points Risk of a cardiac complication (%)

Prior event (e.g. arrhythmia, stroke, heart failure) 0 5

NYHA class[II or cyanosis 1 27

Left heart obstruction [1 75

Systemic ventricular dysfunction

Risk factor in ZAHARA Points scored Total points Risk of a cardiac complication (%)

Prior arrhythmias 1.5 0 2.9

NYHA[2 0.75 0.5–1.5 7.5

Left heart obstruction 2.5 1.51–2.50 17.5

Cardiac medications at baseline 1.5 2.51–3.50 43.1

Systemic AV valve regurgitation 0.75 [3.51 70.0

Sub pulmonary AV valve regurgitation 0.75

Mechanical valve prosthesis 4.5

Cyanotic heart disease 1.0

CARPREG CARdiac Disease in PREGnancy, ZAHARA Zwangerschap bij Aangeboren HARt Afwijkingen I, AV atri-oventricular, NYHA New York Heart Association

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Table 3 Modified World Health Organisation system for risk assessment of cardiac conditions in pregnancy

World Health Organisation systemfor risk assessment

Description

WHO 1 Risk no higher than general population

-Uncomplicated, small or mild pulmonary stenosis, mitral valve prolapse, patent

duct

-Successfully repaired simple lesions such atrial septal defect, ventricular septal

defect, anomalous veins, patent duct

-Isolated atrial or ventricular ectopics

WHO 2 Small increased risk of maternal mortality and morbidity

-Unrepaired simple atrial septal defect/ventricular septal defect

-Repaired Tetralogy of Fallot

-Most arrhythmogenic disorders

WHO 2-3 -Left ventricular dysfunction with ejection fraction[30% and NYHA Class

\III

-Hypertrophic cardiomyopathy

-Non-severe native heart valve disease

-Tissue replacement valve

-Repaired coarctation

-Marfan syndrome without aortic dilatation

-Aorta less than 45 mm in bicuspid aortic valve disease

WHO 3 Significant increased risk of maternal mortality and morbidity. Expert cardiac and

obstetric pre-pregnancy, antenatal and postnatal care required

-Mechanical valve

-Systemic right ventricle

-Fontan circulation

-Unrepaired cyanotic heart disease

-Other complex congenital heart disease

-Aortic dilatation 40–45 mm in Marfan syndrome

-Aortic dilatation 45–50 mm in bicuspid aortic valve disease

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of alterations in measurements during thepregnancy period, with some studies reportingno change and others reporting a small droplate in pregnancy [32, 33]. When assessing leftventricular function there does seem to beagreement across several studies that later inpregnancy the left ventricle becomes moreglobular in shape, accompanied by a drop in leftventricular longitudinal function and strain[32, 34, 35]; this would be in keeping with thelate rise in afterload caused by the slightincrease in SVR [34].

In the assessment of valvular lesions usingechocardiography, pregnancy-related changescan often affect the severity of a valve lesion orthe measurement made by echocardiography.In the context of stenotic valvular lesions, theextra volume load and heart rate increase seenin pregnancy can lead to an increase in thegradient measured across a valve without anyobservable change in the valve area measuredby, for example, the continuity equation [36].When measuring valve regurgitation, it isimportant to note that the extra volume load inpregnancy leads to an increase in observabletricuspid regurgitation without necessarily anychange in the valve function; in contrast, mitralregurgitation, despite the extra volume load,

often appears less during pregnancy due to thedrop in SVR [37]. It is important for cardiolo-gists to undertake serial scans and look at trendsin valve pathology, and these changes need tobe accompanied by clinical assessment.

Cross-sectional imaging can be extremelyvaluable in diagnosis and surveillance duringpregnancy. Cardiac magnetic resonance imag-ing is safe after the first trimester althoughgadolinium injection is not used due to a lack ofdata on its safety [38]. Computed tomographyinvolves ionising radiation but may be requiredin spite of this drawback in life-threateningscenarios, such as a concern about aortic dis-section or pulmonary embolus. Cardiaccatheterisation should be avoided in pregnancybut if required (for example in emergency pac-ing) the radiation dose should be minimised asmuch as possible and lead shielding used acrossthe abdomen to reduce foetal exposure [39].

Common and Important CardiovascularDisorders Encountered During Pregnancy

Specific guidance on some of the more com-monly encountered conditions and importanthigh-risk conditions are discussed in thissection.

Table 3 continued

World Health Organisation systemfor risk assessment

Description

WHO 4 Pregnancy contraindicated: very high risk of maternal mortality or severe

morbidity. Termination should be discussed. If pregnancy continues, care as for

Class 3

-Pulmonary arterial hypertension

-Severe systemic ventricular dysfunction-ejection fraction\30% and NYHA

II-IV

-Severe aortic or mitral stenosis

-Previous peripartum cardiomyopathy with residual LV impairment

-Marfan syndrome with aorta dilated[45 mm

-Aortic dilatation[50 mm in bicuspid aortic valve disease

-Native severe coarctation

WHO World Health Organisation

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Systemic Ventricular DysfunctionThe incidence of systemic ventricular dysfunc-tion solely in pregnancy is difficult to separatefrom dysfunction related to other conditions,but in the European Society of Cardiology’sROPAC registry (Registry Of Pregnancy AndCardiac disease) cardiomyopathies represent 7%of the total registry [40].The normal physiolog-ical changes of pregnancy of increased heartrate, cardiac output and circulating volume areparticularly problematic for women withimpaired systemic ventricular function. Thesewomen often experience a worsening of symp-toms, particularly from around 16 weeks ofgestation. Some women who are not diagnosedprior to pregnancy may be erroneously diag-nosed with asthma or respiratory tract infec-tions before the diagnosis of cardiomyopathy ismade. Ventricular dysfunction due to ischaemicheart disease is very uncommon; most womenhave familial or idiopathic dilated cardiomy-opathy. Some may have had previouschemotherapy or previous peripartum car-diomyopathy. Diagnosis is made clinically andmost commonly in conjunction with echocar-diography, with dysfunction often seen as aworsening on serial echocardiography. Morerecently, medical units have begun to incorpo-rate serial B-type natriuretic peptide (BNP) as amethod for monitoring women with ventriculardysfunction; a worsening in their condition canbe then identified earlier, and BNP is also a goodnegative predictive marker if\100 [41].

Heart failure symptoms in pregnancy shouldbe managed with rest and, as angiotensin-con-verting enzyme inhibitors and angiotensinreceptor blockers are contraindicated, a combi-nation of hydralazine and nitrate can be used toreduce cardiac afterload. Some women mayneed diuretics, although due to the preg-nancy-related increase in glomerular filtrationrate, fewer diuretics than normal may be nee-ded. Beta-blockers can also be a useful adjuncttherapy, and cardo-selective beta-blockers, suchas bisoprolol and metoprolol, are more pre-ferred. Regular foetal growth scans are needed.Careful assessment of the likelihood of thepregnancy reaching viability needs to be asses-sed, and occasionally the decision may be madethat continuing the pregnancy represents too

high a risk to the mother, with advice that thepregnancy be terminated on medical grounds.

Women may require in-patient treatmentand rest, and early delivery may be needed. Thematernal mortality recorded in the ROPAC forcardiomyopathies is 2.4%, but the need forhospital admission is 33% [40]. Prognosis inpregnancy for ventricular dysfunction as illus-trated earlier based on data in the WHO scoringsystem and others is dependent on the level ofventricular dysfunction and symptom severity[27, 42].

Peripartum cardiomyopathy is diagnosedwhen acute left ventricular impairment occursbetween the last 4 weeks of pregnancy and5 months post-partum [43]. The aetiology isunknown, and there is a wide geographicalvariation in frequency, with countries such asHaiti having a particularly high prevalence.Recent experimental work suggests a potentialpathogenic role for prolactin [44] and an over-lap with hypertensive disorders andpre-eclampsia [45]. Treatment should be as forother types of heart failure. Bromocriptine, aprolactin-blocking drug, has been used on acase-by-case basis [46] and in a small trial [47],with some positive results and is currentlyundergoing testing in a larger randomised con-trol trial. The drug has the disadvantage ofprecluding breast-feeding [47], and there maybesome evidence that breast-feeding improvesrecovery in PPCM [48]. Prompt echocardiogra-phy is essential for early diagnosis, and a lowindex of suspicion for the condition is needed.Response to treatment varies widely, with somewomen recovering fully and some requiringheart transplantation or even dying. Positivepredictive factors are early diagnosis, having anejection fraction of [30% or a left ventricularend diastolic dimension of\6.0 cm at the timeof diagnosis [49]. Approximately 50% of womenrecover fully at 6 months and the condition canrecur in 25% women, with those with residualleft ventricular function faring worse in subse-quent pregnancies [50]. Left ventricular recov-ery and survival differs between ethnic groups,with African–American women doing worsethan Caucasians despite comparable treatment[51].

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Left Heart ObstructionIn the ROPAC registry, aortic stenosis andmitral stenosis are the two most common left--sided obstructive lesions, accounting for 31% ofthe valvular heart disease patients seen in theregistry [52]. To date there are insufficient dataavailable worldwide on the incidence of otherobstructive lesions, such subvalvular orsupravalvular lesions or hypertrophic car-diomyopathy with an obstructive gradient. Dueto the extra volume load and inability toincrease cardiac output across a fixed obstruc-tion associated with both aortic and mitralstenosis, these conditions are significantlyproblematic during pregnancy and carry a highrisk of morbidity and mortality [53, 54]. Symp-toms and signs often include increasingbreathlessness, fatigue and oedema, and diag-nosis if unknown prior to conception is usuallyconfirmed with echocardiography.

For mitral stenosis, the mainstay of treat-ment is rest, beta-blockade and diuretics forheart failure symptoms. Percutaneous balloonvalvuloplasty has been widely used in rheu-matic mitral stenosis and should be performedreadily if the woman develops symptoms orfoetal growth is compromised [55]. Aorticstenosis is better tolerated but often moreproblematic as the options for treatment arelimited. It is often due to bicuspid valve disease,and the results from balloon valvuloplasty arenot so predictable or successful. Diuresis is nothelpful, nor is beta-blockade. In both condi-tions, there is an increased risk of prematurityand intra-uterine growth restriction [56]. Inmoderate mitral stenosis and severe aorticstenosis, decisions around delivery often needto be made on a week by week basis as preg-nancy progresses.

ArrhythmiasMany women experience palpitations duringpregnancy that are not of clinical concern, but asmall number of women with pre-existing ornew diagnosed rhythm disorders may needtreatment during pregnancy. Initial manage-ment should be as for any other patient withrhythm disorder: prompt diagnosis based onECG and appropriate medical treatment [57].Safe therapies for tachyarrhythmias during

pregnancy include adenosine, digoxin, fle-cainide and verapamil. Beta-blockers can causeintra-uterine growth restriction, but they are aneffective therapy against most tachyarrhyth-mias in pregnancy. In the context of clinicalcompromise and haemodynamic instability,electrical cardioversion should be used as nor-mal, and no detrimental effects have beenreported on the foetus due to electrical car-dioversion, although foetal assessment after-wards is recommended [58].

Atrial fibrillation should be managed as inthe non-pregnant patient, with attention paidto the need, or not, for anti-coagulation prior toor following a cardioversion.

Catheter ablation is reserved for drug-resis-tant arrhythmias leading to haemodynamiccompromise or refractory symptoms and ifneeded can be performed without fluroscopy[59].

Ventricular arrhythmias (VAs) are much lesscommon in pregnancy than supraventriculararrhythmias and occur most commonly inwomen with known heart disease at a frequencyof approximately 1% [25]. VAs in women withheart disease occur most commonly late inpregnancy, usually in the third trimester withsymptoms of heart failure [60]. Management, asstated earlier, should be as for the non-pregnantwoman, with medications (amiodarone avoi-ded) and defibrillator [implanted cardioverterdefibrillator (ICD)] therapy as needed or emer-gency cardioversion. Pregnancy itself does notseem to lead to an excess of ICD therapies [61].

Congenital long QT syndromes are associ-ated with a risk of syncope and ventriculararrhythmias and a small risk of sudden death.Pregnancy is associated with a reduced risk ofevents during pregnancy but an increased riskof events in the first 9 months post-partum [62],with the risk being most marked for long QT2[62]. It is safe to go through pregnancy with anICD and important not to switch the device offduring delivery. If Caesarean section is requiredunipolar diathermy should be avoided.

Bradyarrhythmias are much less common inpregnancy, and permanent pacing is rarelyrequired [63]; however, if required, radiationexposure should be minimised. Some units have

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suggested isoproterenol can be used safely ifneeded in an emergency situation [64].

Coronary Artery DiseaseCoronary artery dissection, normally a rareoccurrence, is significantly more common inpregnancy, with [20% of all cases of sponta-neous dissection involving pregnant women[65]. However, atherosclerotic coronary arterydisease, which is the major burden of acquiredcardiovascular disease worldwide, is becomingan increasing problem in pregnancy as womenwith traditional cardiovascular risk factors arebecoming pregnant at an older age [66].

The rate of maternal mortality due to anacute coronary syndrome is thought to be5–10% and, as with aortic dissection, peaks inthe peripartum period. Pregnant women pre-senting with chest pain should be assessed inthe usual way with an ECG and appropriatebiomarkers, such as troponin. Traditional riskfactors do determine the risk in the pregnantwoman in the same way as in the normal pop-ulation, and these should be used in the riskassessment.

Treatment of an acute myocardial infarctionshould proceed as normal, with emergencyangioplasty used per guidelines with bare metalstents as these have the widest historical evi-dence base in the pregnant woman [2].Thrombolysis should not be performed ascoronary artery dissection is so often the cause.Clopidogrel as a dual anti-platelet may be addedto the therapeutic regimen for use in as short acourse as possible following stenting; there iscurrently no evidence available for prasugrel orticagrelor. If clopidogrel is prescribed, then theadministration of an epidural is not safe.Although the above caveats need to be borne inmind, the most important part of managementis to treat the mother in the most effective waypossible to save her life.

Congenital Heart DiseaseIn developed countries, most women seen incardiac–obstetric clinics have congenital heartdisease [67]. Due to advances in cardiac surgeryand paediatric intensive care almost all childrenborn with congenital heart disease now survive

to adulthood, with increasingly complex con-ditions. Many of these children want them-selves to have children. Given the widespectrum of lesions and repairs, women withcongenital heart disease should be managedjointly between obstetricians and specialistcardiologists. This spectrum of disorders inpregnancy is reviewed in detail elsewhere [68].

AortopathiesAortopathies, such as Marfan syndrome, presenta significant risk in pregnancy, with increasedblood volume and vascular histological changesleading to increased risks of dissection. Dissec-tion most commonly occurs in the third tri-mester and in the post-partum period, andthose patients with dilated aortas and a familyhistory of dissection are at greatest risk. Type Bdissection is unpredictable. Frequent surveil-lance by ECG during pregnancy is important,and the dissection risk can be reduced bybeta-blockade [69]. Delivery should be highlymedicalised with a combined spinal–epiduraland passive second stage. Very high-risk casesmay need Caesarean section in cardiac theatres.Women should remain in hospital for 1 weekafter delivery.

Women with dilated aortas in the context ofa bicuspid aortic valve are at much less risk ofdissection [70], although regular surveillance byECG during pregnancy is still important, andbeta-blockade and a medicalised delivery maybe recommended if the aorta is particularlydilated.

Turner’s syndrome deserves a special men-tion as some mosaic patients do become preg-nant. Around one-half of women with Turner’ssyndrome will have a cardiac defect (the mostcommon being a bicuspid aortic valve andcoarctation of the aorta). A large number arehypertensive. Moreover, Turner’s syndrome isan independent risk factor for aortic dissection,and these patients should be managed as thosewith Marfan syndrome. It is important to takeaccount of body surface area when measuringaortic size; these women are of small stature andthe absolute aortic measurements may benormal.

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Management of PharmacologicalTreatment in Pregnancy and Post-partum

Women with existing cardiac disorders werepossibly on a variety of medications prior totrying to become pregnant, and the decision tocontinue these medications during pregnancy isbased on balancing the risk to the mother ofstopping them, the availability of a safe alter-native and the risk to the foetus. Due to theethical issue of performing clinical trials inpregnant women the only data on drugs in

pregnancy are from observational studies andbased on evidence from animal trials. Wheneverpossible, prior to conception drugs consideredto be unsafe during pregnancy should be stop-ped. However, many drugs need to be contin-ued in pregnancy, and close liaison with foetalmedicine specialists is important.

A summary of the risk of common cardiacdrugs during pregnancy are listed below inTable 4 [2].

Anti-coagulation is a source of problems inpregnancy. Warfarin is associated with foetal

Table 4 Common cardiac drugs and their risks in pregnancy

Drug Crossesplacenta(yest/no)

In breastmilk (yes/no)

Foetal adverse effects

Angiotensin-converting enzyme

inhibitors/angiotensin receptor

blockers

Commonly Commonly Renal or tubular dysplasia, oligohydramnios, growth

retardation, ossification disorders of skull, lung

hypoplasia, contractures, anaemia, intrauterine death

Adenosine No No No reported effects

Amiodarone Yes Yes Foetal hypothyroidism, bradycardia and growth

retardation

Aspirin Yes Yes No reported effects

Beta-blockers Yes Yes Bradycardia, low birthweight, hypoglycaemia

Clopidogrel Unknown Unknown No information available

Digoxin Yes Yes No reported effects

Dilitiazem No Yes Possibly teratogenic

Flecainide Yes Yes Bradycardia—safe for foetal tachycardia

Furosemide Yes Yes Oligohydraminos

Clexane No No No reported effects

Heparin No No No reported effects

Hydralazine No No Foetal tachyarrhythmias

Methyldopa Yes Yes Mild neonatal hypotension

Nifedipine Yes Yes No reported effects. Tocolytic

Spironolactone Yes Yes Anti-androgenic and cleft abnormalities

Statins Yes Unknown Congenital anomalies

Verapamil Yes Yes No reported effects

Warfarin Yes Yes-inactive Embryopathy, foetal loss, haemorrhage

Cardiol Ther (2017) 6:157–173 167

embryopathy, haemorrhage and a foetal lossrate of up to 35% [39]. Where possible it shouldbe substituted for low-molecular-weight hep-arin (LMWH), which does not cross the pla-centa. However in the case of mechanical valveswarfarin results in significantly less valvethrombosis than unfractionated heparin orLMWH [71, 72]. Some women choose to sub-stitute warfarin with LMWH for the period ofembryopathy risk (6–12 weeks of gestation) andthen resume taking warfarin for most of thepregnancy. Because warfarin crosses the pla-centa, vaginal delivery is unsafe for the foetus,and so warfarin is stopped and substituted withLMWH at 36 weeks. If labour begins prema-turely when the woman is still taking warfarin,a caesarean section must be performed. Somestudies have suggested that doses of[5 mg areassociated with more complications that lowerdoses [73–75], but this finding is not universal[76].

Currently there is no universally agreedupon strategy for the monitoring of enoxaparinuse, with some centres using solely peak ortrough levels of factor Xa, or both [77], and thestrategy decided upon may be particularlyimportant in the first trimester due to largerproportional changes in plasma volume andcreatinine clearance [78].

Management of Labour and Deliveryin Women with Cardiovascular Disorders

The follow-up and delivery of high-risk preg-nancy patients fitting into WHO class 3 [7, 42]should occur in experienced centres wherecombined experienced anaesthetic, obstetric,cardiology and foetal care can be provided.During follow-up visits and assessments in spe-cialist cardiac–obstetric clinic, an individualisedbirth plan is drawn up jointly between the car-diac and obstetric teams, and this formal plan isplaced in each woman’s medical notes so thataccepting teams at non-specialist centres havethe appropriate information for a safe deliveryin an emergency. In many cases labour can beawaited naturally, although in some cases inwhich there is a desire to deliver early due tomaternal complications, or for geographical

reasons to allow for delivery in a specialistcentre, induction of labour may be recom-mended .

Women with cardiovascular disorders havefor many years been subject to a higher rate ofCaesarean sections compared to other women,and it has been suspected that this is due to aclinician’s perception of the risk involved inchanging to an emergency Caesarean section[79]. Caesarean section is associated with moreprofound and sudden haemodynamic changes,greater blood loss, increased risk of infectionand dramatically increased risk of venousthromboembolism [80]. Furthermore, a Cae-sarean section will significantly affect the modeof future deliveries. The combination of a care-fully titrated combined spinal–epidural, passivesecond-stage and assisted delivery with forcepsallow a ‘‘pain free, pushing free labour’’ that ismore physiological and safer for the mother[28, 81]. However, it must be done in experi-enced hands by a specialist team. Caesareansection is reserved for obstetric indications; inrare cases, if there is a very high risk of aorticdissection, a planned delivery in theatres with acardiac surgeon on stand-by is recommended.

The third stage of labour is usually facilitatedby the administration of syntometrine, whichcauses uterine contractions and minimisespost-partum haemorrhage. However, this drugalso has a pronounced hypertensive and vaso-constrictive effect and so is avoided in mostwomen with heart disease in favour of a slowinfusion of syntocinon (an oxytocin analogue)[82]. Misoprostol may be used for post-partumhaemorrhage, with syntometrine reserved onlyfor severe maternal haemorrhage where thebenefit outweighs the risk [82].

POST-PARTUM EVALUATIONAND MANAGEMENT OF WOMENWITH CARDIOVASCULARDISORDERS

Whilst pre-pregnancy assessment and surveil-lance during pregnancy are very important,post-partum follow-up is also important toassess for deterioration following pregnancy

168 Cardiol Ther (2017) 6:157–173

[20] and to monitor for peripartum cardiomy-opathy, which can occur late in the post-par-tum period. Some conditions, such as long QTand Marfan syndrome, seem to be associatedwith more complications in the post-partumperiod, and advising women accordingly isimportant prior to discharge. Post-partum fol-low-up also allows for the reintroduction ofimportant cardiac medications whose use mayhave been altered during pregnancy, such asangiotensin-converting enzyme inhibitors orwarfarin.

Post-partum is a key opportunity to discusscontraception and the options available towomen to reduce the risk of an unplannedpregnancy, as well as to allow recovery from themost recent pregnancy, especially in the con-text of peripartum cardiomyopathy.

CONCLUSION

Pregnancy presents the heart with a uniquephysiological challenge. An increasing numberof women with cardiac disease are goingthrough pregnancy successfully. The range ofconditions encountered is wide, and manypatients have congenital heart disease. Thereare multiple management challenges to achievea successful outcome for mother and child.Pre-pregnancy counselling is vital, and special-ist multi-disciplinary care by a specialist team isessential to ensure a successful outcome formother and child.

ACKNOWLEDGEMENTS

No funding or sponsorship was received for thisstudy or publication of this article. All namedauthors meet the International Committee ofMedical Journal Editors (ICMJE) criteria forauthorship for this manuscript, take responsi-bility for the integrity of the work and havegiven final approval for the version to bepublished.

Disclosures. Reza Ashrafi and Stephanie LCurtis have nothing to disclose.

Compliance with Ethics Guidelines. Thisarticle does not contain any new studies withhuman or animal subjects performed by any ofthe authors.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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