Expert Review of Obstetrics & Gynecology

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Effect of maternal heart disease on pregnancy

outcomes

Emily Gelson & Mark Johnson

To cite this article: Emily Gelson & Mark Johnson (2010) Effect of maternal heart disease on
pregnancy outcomes, Expert Review of Obstetrics & Gynecology, 5:5, 605-617, DOI: 10.1586/
eog.10.49

To link to this article: https://doi.org/10.1586/eog.10.49

Published online: 10 Jan 2014.

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Emily Gelson†1 and
Mark Johnson1
1
Department of Obstetrics and
Gynaecology, Imperial College London,
Chelsea and Westminster Hospital,
369 Fulham Road, London,
SW10 9NH, UK
†
Author for correspondence:
Tel.: +44 208 846 7892
Fax: +44 208 846 7796
egelson@imperial.ac.uk
www.expert-reviews.com
Review
Effect of maternal
heart disease on
pregnancy outcomes
Expert Rev. Obstet. Gynecol. 5(5), 605–617 (2010)
The presence of maternal heart disease has an adverse effect on pregnancy outcomes. The most
recent triennial confidential enquiry confirmed that heart disease is now the most common
cause of maternal death in the UK. Maternal and neonatal morbidity are also significant. This
article details the causes of heart disease and why maternal mortality is increasing. The marked
physiological changes to the cardiovascular system during pregnancy are outlined. The effects
of pregnancy on heart disease are discussed for specific cardiac lesions/conditions, and basic
management principles are described.
Keywords : arrhythmia • cardiomyopathy • congenital heart disease • ischemic heart disease • pregnancy
• valvular heart disease
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Learning objectives
Upon completion of this activity, participants should be able to:
• Identify causes of cardiac morbidity and death in pregnancy, including predictors of primary
cardiac events during pregnancy in women with heart disease
• Examine appropriate anticoagulation regimens in pregnancy for women with mechanical
heart valves and strategies for their incorporation into management
• Describe effects of maternal heart disease and its treatment on fetal outcomes
10.1586/EOG.10.49 © 2010 Expert Reviews Ltd ISSN 1747-4108 605
 Review Gelson & Johnson
Financial & competing interests disclosure
Editor
Elisa Manzotti, Editorial Director, Future Science Group, London, UK.
Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.
CME Author
Désirée Lie, MD, MSEd
Clinical Professor; Director of Research and Faculty Development, Department of Family Medicine, University of California, Irvine, Orange,
California, USA.
Disclosure: Désirée Lie, MD, MSEd, has disclosed the following relevant financial relationship: she served as a nonproduct speaker for: ‘Topics in Health’ for
Merck Speaker Services.
Authors and Credentials
Emily Gelson, BSc (Hons)
Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
Disclosure: Emily Gelson has disclosed no relevant financial relationships.
Mark Johnson, PhD
Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
Disclosure: Mark Johnson has disclosed no relevant financial relationships.
Heart disease is now the leading cause of maternal mortality in the
UK with a mortality rate of 2.27 per 100,000 maternities; double
that reported in 1990 [1] . However, the incidence of heart disease
during pregnancy has remained constant at 0.9% over several
decades [2] , implying that the severity of heart disease and/or the
risk it poses during pregnancy is increasing. The main cause of
this appears to be an increased incidence in previously undiag-
nosed ischemic heart disease. This is due to lifestyle changes, with
increasing numbers of pregnancies in women with risk factors
such as obesity, diabetes and smoking, and also pregnancies in
older women. In addition, women with complex pre-existing heart
disease are surviving into adulthood and considering pregnancy.
Pregnancy in women with heart disease not only poses a risk
of maternal death but also of serious morbidity such as heart fail-
ure, stroke and cardiac arrhythmia. The fetus is not spared, with
neonatal morbidity and mortality due to fetal growth retardation
and prematurity also markedly increased. The causes of maternal
heart disease are diverse and its management complex.
Causes of maternal heart disease
In the developed world, congenital heart disease is now more
common in the pregnant population than acquired heart disease.
This reflects the fact that with advances in cardiac surgery and
medication, 85% of infants with congenital heart disease now
survive into adult life [3,4] . In the UK, the prevalence of congeni-
tal heart disease at birth remains constant at seven per 1000 live
infants but the number of adults with congenital heart disease is
increasing by 1600 per year with a 50% increase in those with
complex disease [5] . By contrast, the rates of maternal death related
to structural congenital heart disease have declined progressively,
suggesting that the level of awareness may have increased and,
thus, may have led to improved management of pregnant women
with various congenital heart defects [6,7] .
Ischemic heart disease is rapidly increasing in the pregnant
population and is now the commonest cause of cardiac death in
pregnancy in the UK [2] . This is likely due to increased mater-
nal age, smoking, the adoption of a sedentary lifestyle and poor
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diet leading to greater rates of obesity, diabetes and hypertension.
Acute myocardial infarction accounts for the majority of deaths
and is most commonly due to coronary atherosclerosis, although
coronary artery dissection and consequent occlusion is also rela-
tively frequent [8] . The risk of an acute myocardial infarction dur-
ing pregnancy is small but increasing, with an estimated incidence
of one in 35,700 deliveries between 1991 and 2000 [9] and one in
16,100 deliveries between 2000 and 2002 [10] .
Consistent with the decline in rheumatic fever in the developed
world, the prevalence of pregnancies complicated by rheumatic
heart disease in the UK has significantly decreased. Rheumatic
heart disease remains prevalent in many developing countries [101] .
The current level of immigration to the UK means that we are
experiencing a resurgence in these cases and it seems inevitable
that the number of pregnant women with rheumatic heart disease
will increase over the coming years. Indeed, the latest confidential
enquiry reported the first maternal deaths due to rheumatic heart
disease since 1991–1993 and both were in recent immigrants [1] .
Pregnancy-induced cardiomyopathy is a disorder in which left
ventricular systolic dysfunction and heart failure present in the
last month of pregnancy and the first 5 months postdelivery, in
the absence of all other causes of dilated cardiomyopathy with
heart failure. It is a rare condition with an estimated incidence of
1 case per 5000–10,000 live births [11] . However, it is one of the
most common causes of maternal death in the UK [1] .
Cardiac arrhythmias are also an important cause of maternal
morbidity. Pregnancy increases the incidence of cardiac arrhyth-
mia. This is due to hormonal changes, alterations in autonomic
tone, increased hemodynamic demands and mild hypokalemia.
These factors act to precipitate cardiac arrhythmias not present
prior to pregnancy or exacerbate pre-existing arrhythmias. The
risk is highest during labor and delivery.
Physiological changes in normal pregnancy
During normal pregnancy there are dramatic alterations in
cardio­vascular physiology, initiated by a fall in systemic vascular
resistance to 30–70% of its preconception value by 8 weeks of
Expert Rev. Obstet. Gynecol. 5(5), (2010)
 CME Effect of maternal heart disease on pregnancy outcomes
gestation (Box 1) [12] . The mechanism(s) responsible for triggering
such widespread vasodilatation is unclear but increased circu-
lating levels of estrogens, vasodilatory peptides or factors such
as nitric oxide and calcitonin gene-related peptide have all been
suggested to be responsible. The fall in systemic vascular resis-
tance results in fluid retention and an increased blood volume.
Since there is a relatively greater expansion in plasma volume, this
results in a fall in hematocrit and plasma osmolality. The increase
in cardiac output is secondary to a greater stroke volume and
higher heart rate. It rises to a peak between the 20th and 24th
weeks and remains stable until term. Arterial blood pressure falls
until mid pregnancy, gradually returning to prepregnancy levels
late in the second trimester. Prolonged volume overload results in
progressive physiological left ventricular hypertrophy.
Labor, particularly the second stage, is associated with a further
increase in cardiac output. Pain induces a sympathetic response
causing an increase in heart rate. Stroke volume is augmented
by autotransfusion during contractions. Following delivery the
return of uterine blood into the systemic circulation results in
a further increase in cardiac output. Stroke volume, heart rate
and cardiac output remain high for 24 h postdelivery with rapid
intravascular volume shifts in the first 2 weeks postpartum. Thus,
the later stages of labor and early postpartum are periods of high
risk of pulmonary edema.
Effect of pregnancy on heart disease
In the presence of maternal heart disease, such a dramatic altera-
tion in the cardiovascular system may ultimately lead to cardiac
decompensation or death. Risk to the mother with heart disease
appears to be determined primarily by the ability of their cardio-
vascular system to adapt to pregnancy. As such, different cardiac
lesions carry specific mortality risks, dependent on current hemo-
dynamic status, previous operations and anatomical features [13] .
The cardiac conditions of highest risk are pulmonary vascular
disease, Marfan syndrome with a dilated aortic root, left-sided
obstructive lesions and a dilated poorly functioning left ventricle.
Pregnancy also poses the risk of serious maternal morbidity. The
only large prospective study of pregnancy outcomes in women
with congenital heart disease to date identified 546 women with
congenital heart disease with 599 pregnancies. This showed a
combined maternal, fetal and neonatal mortality of 3% [6] . The
rate of primary cardiac event, the most common of which was
pulmonary edema, was 13%. In a multivariate analysis, the most
significant predictor of morbidity and mortality was the presence
of left ventricular dysfunction. Predictors of adverse maternal
outcomes are listed in Box 2 .
Other studies combining congenital and acquired heart disease
have mainly arisen from the developing world, where rheumatic
heart disease is the most predominant cardiac lesion encoun-
tered  [14–22] . These retrospective studies demonstrate a high
rate of cardiac complication ranging from 11.11 to 30% and a
maternal mortality rate of 2–3.3%. Higher rates of both mater-
nal morbidity and mortality were seen in women with poorer
cardiac New York Heart Assiciation (NYHA) functional class
at baseline [14–16] .
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Review
Box 1. Physiological changes in normal pregnancy.
• Decreased systemic and pulmonary vascular resistance
• Increased blood volume
• Initial fall in blood pressure to 20 weeks followed by an increase
until term
• Increased heart rate
• Increased stroke volume
• Increased cardiac output
• Physiological cardiac hypertrophy
• Pulmonary capillary wedge pressure unchanged
Pregnancy in specific conditions
Left to right shunts
In pregnancy, increased cardiac output and blood volume are
counterbalanced by a decrease in peripheral vascular resistance.
Left-to-right shunting in patients with atrial septal defects (ASDs),
ventricular septal defects and patent ductus arteriosus is therefore
reduced. In the absence of pulmonary hypertension, pregnancy,
labor and delivery are well tolerated [23] . Patients with ASDs are
at risk of atrial arrhythmia and paradoxical embolism. As such
there is a low threshold for prophylaxis with either aspirin alone
or with heparin if other risk factors are present.
Right-sided heart lesions
Right-sided heart lesions lead to abnormal loading of the right
ventricle (Table 1) . During pregnancy, increased blood volume and
heart rate put a considerable strain on the right side of the heart,
leading to enlargement of the right ventricle [24] .
Pulmonary stenosis
Isolated pulmonary stenosis is usually well tolerated during preg-
nancy [25] . However, the increased cardiac output of pregnancy
can lead to increased right-ventricular pressure and, in severe pul-
monary stenosis, this may lead to right-ventricle failure and/or
atrial arrhythmia.
Tetralogy of Fallot
Tetralogy of Fallot (TOF) is the most common form of cyanotic
congenital heart disease. It is characterized by a nonrestrictive
ventricular septal defect, aortic override, pulmonary stenosis and
right-ventricular hypertrophy. In developed countries, TOF is
usually corrected surgically in infancy, well before pregnancy
Box 2. Predictors of adverse maternal outcomes.
• Prior cardiac event (heart failure, transient ischemic attack or
stroke) or arrhythmia
• Baseline New York Heart Association class greater than II
or cyanosis
• Left heart obstruction (mitral valve area <2 cm2, aortic valve
area <1.5 cm2, or peak ventricular outflow tract gradient
>30 mmHg by echocardiography)
• Reduced systemic left-ventricular function (ejection
fraction <40%)
Data taken from [6].
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 Review Gelson & Johnson
Table 1. Right-sided heart lesions.
Volume overload Pressure overload
Pulmonary regurgitation Pulmonary stenosis
Ebsteins anomaly of the tricuspid valve l-TGA
Repaired TOF d-TGA after atrial switch
d-TGA: Dextro-TGA; l-TGA: Levo-TGA; TGA: Transposition of the great arteries;
TOF: Tetralogy of Fallot.
is contemplated, and it is generally accepted that pregnancy in
women with repaired TOF is well tolerated in this context [26] .
However, complications such as arrhythmias and right-ventric-
ular failure do occur, particularly in the presence of residual
shunts, right-ventricular outflow obstruction and pulmonary
hypertension. Careful assessment including echocardiography
is advisable prior to pregnancy. Many TOF patients will have
significant pulmonary regurgitation. The presence of severe pul-
monary regurgitation and/or subpulmonary ventricular systolic
function has been shown to be associated with adverse maternal
and neonatal outcomes [27,28] . This needs to be discussed prior
to pregnancy, and in some cases pulmonary valve replacement
may be advisable.
Ebstein’s anomaly of the tricuspid valve
Ebstein’s anomaly is a malformation of the tricuspid valve con-
sisting of apical displacement of the tricuspid valve, resulting
in tricuspid regurgitation and enlargement of the right atrium.
In the absence of cyanosis, right-sided heart failure or arrhyth-
mias (Ebstein’s is often associated with a re-entrant tachycardia)
­pregnancy is usually well tolerated [29] .
Transposition of the great arteries
In transposition of the great arteries, the aorta arises from the
morphological right ventricle and the pulmonary artery from the
morphological left ventricle. The atrial switch procedure intro-
duced in the 1950s has enabled survival beyond infancy. In this
procedure, venous blood flow is redirected within the atrial com-
partment leaving the morphological right ventricle and tricuspid
valve supporting the systemic circulation. Although survival rates
are favorable, a number of potential long-term complications
exist. These include failure of the systemic right ventricle, tri-
cuspid regurgitation, sinus node dysfunction, arrhythmias and
baffle obstruction (venous pathway obstruction). Pregnancy
is well tolerated following an uncomplicated repair; however,
right ventricular dysfunction and/or atrial arrhythmia may still
occur [30] . In patients with long-term complications, pregnancy
is poorly tolerated with an increased risk of cardiac complica-
tions [31] . Many patients with corrected transposition of the great
arteries are on angiotensin convertase (ACE) inhibitors, which
should ideally be stopped preconception, as they are associated
with fetal nephrotoxicity and congenital malformations [32] . More
recently, complete repair has been by the Jatene procedure, in
which the great vessels are transplanted to their correct anatomi-
cal sites. The outcome of pregnancy in these patients remains to
be seen but recent case reports are promising [33] .
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Univentricular hearts after Fontan-type procedure
The Fontan-type procedures have become recognized as the defini-
tive palliative procedure available for complex cyanotic heart defects
characterized by a single functional ventricle. Atrial separation
divides the systemic and pulmonary circulations, and with the
construction of atrio–pulmonary connections blood enters the pul-
monary circulation without pulsatile ventricular flow. Increasing
numbers of patients with a Fontan circulation are reaching child-
bearing age. The major concern regarding pregnancy in women
with a Fontan circulation is their ability to augment, maintain
and adjust cardiac output and heart rate. There is also a tendency
towards atrial arrhythmias, which are poorly tolerated. Recent stud-
ies suggest that the maternal risk of pregnancy is low in NYHA
class I–II patients, provided ventricular function is good [34] .
Left-sided heart lesions
Owing to a fall in peripheral vascular resistance, left-sided val-
vular regurgitant abnormalities are generally well tolerated in
pregnancy. However, the increased stroke volume of pregnancy
and delivery can have profound effects in the presence of left-sided
stenotic valvular abnormalities.
Mitral stenosis
Rheumatic mitral stenosis is the most common clinically signifi-
cant valvular lesion in pregnancy. During pregnancy, the rise in
heart rate and stroke volume increases the pressure gradient across
the narrowed mitral valve. This leads to an increase in left atrial
pressure and potentially the development or worsening of symp-
toms, including dyspnea, decreased exercise capacity, orthopnea,
paroxysmal nocturnal dyspnea and pulmonary edema. The risk
of deterioration persists into the puerperium. Increased left-atrial
pressure also increases the risk of atrial fibrillation, which may lead
to an uncontrolled ventricular rate and heart failure. Mortality
among pregnant women with minimal symptoms is less than
1%  [35] . Women with severe symptoms (NYHA class III or IV)
or severe stenosis (valve area <1 cm) should delay conception until
surgical correction. During pregnancy, medical therapy is directed
at minimizing volume overload with bed rest and diuretics and
optimizing ventricular filling with b-blockade. Atrial fibrillation
requires prompt treatment with direct current (DC) cardioversion,
b-blockers or digoxin. Balloon mitral valvuloplasty is indicated with
refractory symptoms despite optimal medical therapy and is safe
and effective during pregnancy, with favorable long-term results [36] .
Mitral valve prolapse
Mitral valve prolapse (MVP) is the most common cardiac abnor-
mality in the pregnant population, affecting 12–17% of women
of childbearing age. MVP without regurgitation does not affect
the cardiovascular response to pregnancy and thus seldom gives
rise to cardiovascular complications [37] .
Mitral regurgitation
Mitral regurgitation during pregnancy is usually a result of rheu-
matic valvular disease or MVP. Owing to the fall in systemic
vascular resistance and reduced left-ventricular afterload, mitral
Expert Rev. Obstet. Gynecol. 5(5), (2010)
 CME Effect of maternal heart disease on pregnancy outcomes
regurgitation in the absence of left ventricular dysfunction is usu-
ally well tolerated during pregnancy [38] . Asymptomatic patients do
not require therapy during pregnancy. Symptomatic heart failure
can be treated with nitrates, hydralazine, diuretics and digoxin.
Aortic stenosis
In young women, aortic stenosis (AS) is usually congenital in ori-
gin. The limited ability of the left ventricle to augment cardiac
output results in an abnormal elevation of left-ventricular systolic
and filling pressures, leading to a compensatory left-ventricular
hypertrophy. During pregnancy, the increase in stroke volume
and fall in systemic vascular resistance lead to an increase in the
gradient across the aortic valve [39] . The clinical consequences of
the increased aortic gradient depend on the degree of pre-existing
left-ventricular hypertrophy and left-ventricular systolic function.
When compensatory changes in the left ventricle are inadequate
to meet the demands imposed by the need for increased cardiac
output late in pregnancy, symptoms develop. Moderate-to-severe
AS (valve area <1.5 cm2) has a significant impact on pregnancy out-
come. Recent studies report no maternal or neonatal deaths; how-
ever, moderate-to-severe AS is associated with significant maternal
morbidity including heart failure, arrhythmia and syncope [40] .
Women who are symptomatic or who have severe stenosis (peak
outflow gradient >80 mmHg) or left ventricular dysfunction are
advised to delay conception until after surgical correction. If a
pregnant woman becomes symptomatic or is so at the time of preg-
nancy, diagnosis then bed rest should be advised and a full assess-
ment carried out. Although valve replacement can be considered,
wherever possible open heart surgery, with the need for cardiac
bypass, should be avoided as it carries a 1.5–5% risk of maternal
mortality and a 16–33% risk of fetal mortality, independent of ges-
tational age [41] . Fetal mortality can, however, be reduced to 10%
by avoiding hypothermia and maintaining perfusion pressures.
Aortic balloon valvuloplasty may be used as a palliative procedure,
allowing deferral of valve replacement until after birth [42] .
Aortic regurgitation
Aortic regurgitation in young women is usually due to congenital
bicuspid valve, rheumatic heart disease, endocarditis or dilated
aortic annulus. In the absence of left ventricular dysfunction,
aortic regurgitation is usually well tolerated during pregnancy [39] .
This is due to the combination of a fall in systemic vascular resis-
tance and an increase in heart rate, which shortens diastole and
thus the degree of regurgitation.
Prosthetic heart valves
Bioprosthetic heart valves in the presence of a normally function-
ing left ventricle and the absence of pulmonary hypertension are
not associated with increased risk during pregnancy. Some reports
have suggested that pregnancy accelerates structural degeneration
of bioprosthetic valves [43,44] . However, several recent large series
have failed to confirm this [45–47] .
Patients with mechanical heart valves require lifelong anticoagu-
lation to reduce the risk of thrombotic events. During pregnancy,
the risk of thrombosis increases further owing to the hypercoaguable
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Review
state. As such, pregnancy in women with mechanical valve replace-
ment is associated with marked maternal morbidity and potential
mortality with a 25% incidence of thrombotic episodes (stroke,
valve thrombosis and myocardial infarction) and a maternal mor-
tality rate of 1–4% [48] . Effective anticoagulation is critical and
the risk to the mother and fetus need to be carefully balanced.
Controversy still exists regarding the safest and most efficient
anticoagulant regimen to use. The types of anticoagulation that
can be used during pregnancy include warfarin, unfractionated
heparin and low-molecular-weight heparin. Warfarin is the best
therapeutic option for the mother but it carries a risk of warfarin
embryopathy and fetal loss. Heparin does not cross the placenta
and as such does not affect the fetus. It is, however, associated with
an increased risk of thrombotic events compared with warfarin.
Unfractionated heparin can be used during pregnancy but is prob-
lematic, with an attenuated response of activated thromboplastin
time (aPTT), variable sensitivities of aPTT reagents and wide peaks
or troughs with the use of subcutaneous unfractionated heparin.
The long half-life of low-molecular-weight heparin allows better
control of anticoagulation than unfractionated heparin provided
that anti-Xa concentrations are closely monitored, maintaining
values greater than 1. A recent study by McLintock et al. reports
on 34 pregnancies in women with mechanical heart valves treated
with predominantly low-molecular-weight heparin [49] . Thrombotic
complications occurred in 10.6% of pregnancies. Noncompliance
or subtherapeutic anti-Xa levels contributed in each case, suggesting
that therapeutic doses of low-molecular-weight heparin are associ-
ated with a low risk of thrombosis. The available regimens and risk
of maternal and fetal complications are listed in Table 2. Warfarin is
stopped at week 36 to allow the fetus to metabolize it before delivery,
thereby reducing the risk of hemorrhage.
Aortopathies
Pregnancy has been associated with an increased risk of aortic dis-
section in the general population [50] . This is probably due to the
combination of an increased cardiac output and blood volume and
hormonal changes that weaken the aortic wall. Women with known
aortopathy are at increased risk, particularly near term or postnatally.
Marfan syndrome
Marfan syndrome is an inherited disorder of connective tissue. A
total of 80% of Marfan patients have some cardiac involvement,
usually MVP, mitral regurgitation, aortic root dilatation and/or
aortic incompetence. In women with Marfan syndrome, pregnancy
increases the risk of thoracic aortic aneurysm leading to aortic dis-
section, rupture, or both. The risk appears to be dependent on
aortic root diameter. With an aortic root less than 4 cm, the overall
maternal mortality during pregnancy is 1%. This increases to as
much as 25% as the aortic root diameter expands beyond 4 cm [51] .
In this situation, pregnancy should be postponed until after aortic
arch replacement [52] . In the event of an unplanned pregnancy, the
option of termination of pregnancy should be discussed. Aortic root
diameter should be monitored throughout pregnancy with serial
echocardiograms and if aortic root dilatation occurs, prophylactic
b-blockade is advised. Hypertension should be treated aggressively.
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 Review Gelson & Johnson
Table 2. Anticoagulation regimens in pregnancy for women with mechanical heart valves.
Regimen Maternal complication
Thrombotic events (%) Death (%)
Warfarin until week 35, then heparin 3.9
until delivery
Unfractionated heparin until week 13, 9.2
then warfarin until week 35, then heparin
until delivery
Low-molecular-weight heparin 10.6
throughout pregnancy
Unfractionated heparin 33.3
throughout pregnancy
With any of the above regimens, consider adjunctive antiplatelet therapy in the second and third trimester.
NA: Not available.
Data taken from [48,49].
Coarctation of the aorta
Coarctation of the aorta occurs in 6–8% of patients with congeni-
tal heart disease. The majority of cases are diagnosed in infancy
or childhood and are either surgically corrected or treated by
balloon dilatation or stent implantation. Women with repaired
coarctation of the aorta are expected to reach childbearing age. By
contrast, native coarctation is encountered much less frequently.
Pregnancy is usually well tolerated in adequately repaired coarcta-
tion [53] . It is essential to assess cardiac status prior to conception,
excluding and appropriately managing complications such as re-
coarctation, aneurysm at the site of repair, an associated bicuspid
aortic valve or systemic hypertension. In both corrected and native
coarctation, pregnancy poses the risk of aortic dissection and rup-
ture, and resistant hypertension. Poorly controlled hypertension
may lead to pre-eclampsia, hypertensive crisis and rupture of an
intracranial aneurysm and, as such, needs to be tightly controlled
with b-blockers as the first-line agent.
Bicuspid aortic valve disease
The presence of a bicuspid aortic valve is associated with proximal
aortic aortopathy. This can occur in the presence of coarctation
of the aorta and/or AS. This form of aortic root dilatation during
pregnancy is predisposed to aortic dissection, particularly in the
third trimester [54] . If the aortic root is dilated at diagnosis then
it should be closely monitored with monthly echocardiograms.
Where the aortic root diameter is less than 4 cm it should be
monitored with echocardiograms in each trimester. Symptoms
of dissection should be promptly investigated with echocardio-
gram and computed tomography, accepting that there is a risk of
radiation exposure.
Cyanotic heart disease
Cyanotic heart disease without pulmonary hypertension is caused
by persistent truncus arteriosus, uncorrected TOF with pulmo-
nary stenosis/atresia, univentricular heart, tricuspid atresia and
Ebstein’s anomaly with ASD. During pregnancy the fall in sys-
temic vascular resistance and rise in cardiac output exacerbates
any right-to-left shunting worsening pre-existing cyanosis and
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Fetal complications
Fetal anomalies (%) Fetal wastage (%)
1.8 6.4 33.6
4.2 3.4 26.5
0 NA 4
15 0 42.9
hypoxia. Maternal complications depend mainly on ventricular
function and include hemorrhage, thromboembolism (owing to
polycythemia secondary to hypoxia) and heart failure [55] .
Pulmonary hypertension
Pregnancy in the presence of pulmonary hypertension of any
cause remains high risk. Fixed pulmonary vascular resistance
prevents any increase in pulmonary blood flow to match the
increased cardiac output. Pregnancy is poorly tolerated with a risk
of worsening cyanosis and hypoxia, arrhythmias, heart failure
and death. The majority of complications occur at term or during
the first postpartum week. Maternal mortality depends on the
underlying cause, with mortality rates of 36% in Eisenmenger’s
syndrome, 30% in primary pulmonary hypertension and 56%
in secondary pulmonary hypertension reported [56] . Patients
should be advised of these risks when contemplating pregnancy.
Anticoagulation, oxygen therapy and pulmonary vasodilators
(sildenafil, nitric oxide or prostacyclin [endothelin antagonists
are contraindicated in pregnancy]) may improve outcome [57] .
The postpartum period is particularly high risk for maternal
mortality and, as such, ­high‑dependency care should continue
for several days postdelivery.
Ischemic heart disease
Acute myocardial infarction is relatively rare during pregnancy
and the puerperium. However, the risk of mortality is high at
5–20% for the mother and 9–19% for the baby [8–10] . Pregnancy
itself has been identified as a risk factor for acute myocardial
infarction owing to the increased blood volume, altered hemo-
dynamics and hypercoaguable state [8] . There is a high incidence
of known risk factors for atherosclerosis in pregnant patients who
suffer an acute myocardial infarction during pregnancy and the
postpartum period [9] . Hyperlipidemia, hypertension and dia-
betes have the potential to be better controlled preconception,
and smoking cessation and avoidance of excessive weight gain
can be strongly encouraged. To reduce maternal morbidity and
mortality, prompt diagnosis and treatment is essential. Once
myocardial infarction is diagnosed, acute phase intervention
Expert Rev. Obstet. Gynecol. 5(5), (2010)
 CME Effect of maternal heart disease on pregnancy outcomes
should not be withheld. The treatment of choice is percutaneous
coronary catheterization. If this is not available, thrombolysis
should be considered.
Cardiac arrhythmias
Pregnancy increases the incidence of cardiac arrhythmia. The risk
of both new onset and exacerbation of supraventricular tachycardia
(SVT) is increased during pregnancy [58] . Atrial fibrillation and
atrial flutter are rare and may be caused by pre-existing congenital
or valvular heart disease, thyrotoxicosis or electrolyte imbalance.
Owing to the risk of thromboembolism and the potential detri-
mental effect on the fetus, early treatment is important either with
conversion to sinus rhythm or ventricular rate control. Other causes
of SVT encountered in pregnancy are re-entrant tachycardia, for
example Wolf–Parkinson–White syndrome and Lown–Levine–
Ganong syndrome. Initial treatment in the hemodynamically stable
patient to terminate an SVT should involve the vagal maneuver.
If this fails, intravenous adenosine may be safely used. Second-
line treatments include digoxin, b-blockers and calcium-channel
blockers. Ventricular tachycardia is uncommon in pregnancy. It is
usually associated with underlying heart disease, but new onset of
ventricular tachycardia without structural heart disease has been
reported [59] . Initial therapy with lidocaine or procainamide should
be considered in hemodynamically stable patients. Amiodarone is
relatively contraindicated, as it is associated with fetal hypothy-
roidism, growth retardation and prematurity, although it has been
recently used to control fetal tachyarrhythmias. b-blockers and
sotalol are used prophylactically. Electrical cardioversion is safe
in pregnancy and necessary in all patients with tachyarrhythmias
who are hemodynamically unstable [59] . Attention should be paid
to airway management to reduce the risk of aspiration/regurgita-
tion of gastric content and care should be taken to avoid the supine
position and thus aortocaval compression.
Cardiomyopathy
Dilated cardiomyopathy
Increased intravascular volume and cardiac output during preg-
nancy is poorly tolerated in patients with dilated cardiomyopa-
thy, potentially leading to cardiac decompensation. Moderate/
severe left-ventricular dysfunction and NYHA class greater than
II are predictive of adverse cardiac events [60] . Patients should be
advised of these risks when contemplating pregnancy. In the event
of an unplanned pregnancy a termination of pregnancy should
be offered.
Hypertrophic cardiomyopathy
Clinical and genetic screening of families with hypertrophic car-
diomyopathy and the widespread use of echocardiography has
led to the identification of increasing numbers of women with
hypertrophic cardiomyopathy who would have previously been
unaware of their condition. Pregnancy in asymptomatic women
is usually well tolerated [61] . However, in those women with heart
failure or severe symptoms prior to pregnancy, there is a risk of
symptomatic progression, atrial fibrillation, syncope and maternal
death [62] .
www.expert-reviews.com
Review
Peripartum cardiomyopathy
Peripartum cardiomyopathy (PPCM) is thought to be caused by
the interaction of several factors, including hemodynamic stress,
genetics, immune dysregulation and fetal microchimerism. The
severity of symptoms varies from catastrophic to subclinical. Recent
mortality rates of approximately 30% have been reported  [63,64] ,
with 50% of women recovering normal left-ventricular func-
tion [65] . Adequate treatment with b-blockers, diuretics, hydrala-
zine and digoxin reduce mortality rates and improve overall prog-
nosis. Subsequent pregnancy after a diagnosis of PPCM carries
higher risk of relapse if left-ventricular systolic function is not fully
recovered first; and even with full recovery, some additional risk of
relapse remains [66] . Recent data suggested a role for prolactin in
the pathophysiology of PPCM and a proof-of-concept study has
shown that bromocriptine may be of benefit [67] .
Effect of heart disease on pregnancy outcomes
Obstetric complications
The presence of heart disease does appear to increase the risk of
obstetric complication. In a retrospective study of 112 pregnancies
in women with congenital heart disease, Ouyang et al. report a
32.6% rate of adverse obstetric outcomes [68] . Preterm delivery
and postpartum hemorrhage were the most frequent complica-
tions seen. Preterm delivery was due to preterm premature rup-
ture of membranes and indicated deliveries. The increased rate
of postpartum hemorrhage is probably due to an increased rate of
planned assisted delivery. However, the use of anticoagulation in
the peripartum period and cyanosis are independent predictors of
postpartum hemorrhage [6] . The only cardiac lesion with specific
increased risks is coarctation of the aorta, which is associated with
an increased risk of pregnancy-induced hypertension [6] .
If obstetric complications do occur, this can have significant
impact on the outcomes of pregnancy. For example, pre-eclampsia
increases the risk of cardiac decompensation and death and post-
partum hemorrhage can lead to hypovolemic shock, which is often
poorly tolerated. The relative immunocompromise of pregnancy
increases the risk of infection (e.g., urinary tract infection). This
can increase the heart rate, potentially worsening cardiac function.
Fetal & neonatal outcomes
The presence of maternal heart disease impacts on the fetus in
a number of ways. First, the risk of spontaneous miscarriage
and therapeutic abortion is increased in women with heart
disease  [7] . The offspring of a mother with congenital heart
disease are also at increased risk of inheriting a congenital heart
disease. The overall risk of the offspring inheriting polygenic
cardiac disease is quoted at 3–5%, compared with a 1% risk
in the general population [69] . The risk is, in fact, dependent
on the affected parent’s condition and there is an increased
risk if a previous sibling has been affected (Table 3) [70] . Certain
cardiac medications can adversely affect the fetus (e.g., ACE
inhibitors, warfarin and statins). ACE inhibitors are known to
have teratogenic effects in the first trimester and should there-
fore be avoided during this period [71] . Exposure in the second
and third trimester can lead to marked fetal hypotension and
611
 Review Gelson & Johnson CME

lesions. In women with Marfan syndrome a prospective study of

Table 3. Risk of congenital heart disease in the
aortic root growth during pregnancy compared mean aortic root
offspring of women with heart disease.
size in 23 women undergoing pregnancy with 22 women who
Cardiac lesion Risk of CHD in fetus (%) did not become pregnant. There was no difference in the rate of
Previous sibling Father Mother aortic expansion during a 6.4‑year follow-up [75] . In women with
affected affected affected AS, pregnancy has been shown to have an adverse effect on the
Marfan syndrome – 50 50
heart, with higher rates of cardiac intervention and late cardiac
events seen in women who have undergone pregnancy compared
Aortic stenosis 2 3 15–17.9
with matched controls who have not been pregnant [76] . Data
Pulmonary stenosis 2 2 6.5 also suggest that pregnancy has an irreversible deleterious effect
VSD 3 2 9.5–15.6 on ventricular function in women with TOF [25] , peripartum
­cardiomyopathy and a systemic right ventricle [29] .
ASD 2.5 1.5 4.6–11
PDA 3 2.5 4.1 Management principles
COA – – 14.1 Although strict protocols for the management of heart disease in
TOF 2.5 1.5 2.6 pregnancy do not exist, a number of basic principles can be applied.
ASD: Atrial septal defect; CHD: Congenital heart disease; COA: Coarctation of
the aorta; PDA: Patent ductus arteriosus; TOF: Tetralogy of Fallot; Prepregnancy counseling
VSD: Ventricular septal defect.
Data taken from [69,70]. The management of women with heart disease should ideally take
place before conception. In women with congenital lesions this
decreased (fetal) renal blood. Where ACE inhibitors must be process should begin during adolescence with discussions about
continued, the lowest possible dose should be used and amni- family planning, contraception and pregnancy.
otic fluid levels and fetal growth should be monitored carefully. Women with heart disease contemplating pregnancy should
Statins have been identified as potential teratogens on the basis be assessed in a multidisciplinary prepregnancy clinic (staffed
of theoretical considerations. However, epidemiological data by an obstetrician, cardiologist, anesthetist and midwife). A full
suggest that statins are not major teratogens. Given the scarcity cardiac assessment should be performed. The history should
of available data, it is still advisable to avoid statins during the focus on the patients’ exercise capacity and past cardiac events.
first trimester [72] . Echocardiography should assess cardiac hemodynamics including
The rate of neonatal complication is significantly increased in valve areas and pulmonary pressures. In patients with impaired
women with heart disease. Siu et al. in their prospective longitu- functional capacity an exercise test with maximum oxygen uptake
dinal study of pregnancy outcomes in women with heart disease refines risk stratification for pregnancy. These risks should be
reported neonatal outcomes in 302 pregnancies [7] . Neonatal discussed with the woman and her family and a risk of maternal
complications occurred in 18% of pregnancies. Preterm deliv- morbidity and mortality quoted.
ery occurred in 15%, fetal growth restriction in 4%, respira- Patients should be assessed and counseled regarding their need for
tory distress syndrome or intraventricular hemorrhage in 2% any medical, interventional or surgical treatment prior to concep-
and neonatal death in 3% of pregnancies. Predictors of adverse tion. Avoidance of pregnancy should be advised for patients with
neonatal outcomes were NYHA class greater than II, cyanosis, pulmonary hypertension, Eisenmenger’s syndrome or Marfan’s syn-
maternal left-ventricular obstruction, maternal smoking, mater- drome with an aortic root diameter greater than 4 cm. Contraception
nal age under 20 years or over 35 years, multiple gestation and should also be discussed as a means of delaying or preventing preg-
anticoagulation during pregnancy. nancy [77] . A sensitive yet important issue that should be addressed
Neonatal complications are particularly high in women with with the mother and her family is her capacity to care for a child and
cyanotic heart disease and in women with a Fontan repair [73] . her overall life expectancy. The risk of ­recurrence of heart disease
Pregnancy is associated with a high incidence of fetal loss, still- in the offspring should also be considered.
birth, fetal growth restriction and preterm delivery [74] . In cya-
notic heart disease, the risk increases significantly when maternal Antenatal care
oxygen saturations fall below 85% (Table 4) . This should be dis- Once pregnant, women should be cared for by medical person-
cussed prepregnancy and the fetus should be monitored carefully nel who are experienced in the management of pregnant patients
throughout pregnancy. with heart disease. A multidisciplinary approach should be applied
including obstetricians, cardiologists, anesthetists and neonatolo-
Long-term effects of pregnancy gists. Regular antenatal checks are advised throughout pregnancy.
There are limited data on the effects of pregnancy on long-term The purpose of antenatal care is to ensure the continued well­being
outcomes in women with heart disease. Most data focus on mater- of the mother and fetus. Prompt treatment of anemia, urinary
nal outcomes during pregnancy, but the impact of the hemody- tract infection and arrhythmias are important; intervention before
namic burden of pregnancy (whether positive or negative) beyond major cardiac decompensation and the early diagnosis and manage-
the pueperium is not clear. There are some published data for some ment of preeclampsia can prevent significant problems. Medication

612 Expert Rev. Obstet. Gynecol. 5(5), (2010)

 CME Effect of maternal heart disease on pregnancy outcomes
should be reviewed and teratogenic drugs stopped and an alterna-
tive used where possible. In general, warfarin should be changed
for low-molecular-weight heparin for the duration of pregnancy,
except in the case of metallic heart valves. In certain circumstances,
specific therapy is required, including avoidance of vasodilators
to maintain preload, empirical b-blockers in Marfan’s syndrome
and prophylactic heparin in pregnancy complicated by pulmo-
nary hypertension. Admission for bed rest and monitoring may be
required and is advised with a NYHA class greater than III.
As there is an association between increased nuchal thick-
ness and cardiac defects in both chromosomally abnormal and
normal fetuses, fetal assessment should involve a nuchal translu-
cency scan early in pregnancy. A fetal echogram should be per-
formed between 18 and 22 weeks with a routine anomaly scan at
20 weeks. The assessment of fetal growth with serial ultrasound
scans is essential in women with heart disease, especially if this
is in the form of cyanotic heart lesions.
Labor & delivery
The appropriate timing for delivery is crucial to balance both
maternal and neonatal mortality and morbidity. Labor and deliv-
ery require careful planning. Vaginal delivery is recommended in
most women with heart disease. There is no direct evidence to link
mode of delivery with outcome; however, it is known to be associ-
ated with a smaller shift in blood volume, hemorrhage, clotting
and infection. In the absence of infection, infective endo­carditis
prophylaxis is not recommended except in high-risk patients.
Labor and delivery are an additional burden on the maternal
cardiovascular system and requires continuous monitoring of both
mother and fetus. Maternal preload, blood pressure and blood loss
should be monitored carefully throughout, with invasive moni-
toring occasionally required. Low-dose epidural with adequate
volume loading does not decrease systemic vascular resistance and
is thus the analgesia of choice. The length of the second stage may
be shortened by elective assisted delivery to avoid excessive mater-
nal effort. During the third stage of labor bolus doses of oxytocin
should be avoided as they result in an initial fall in arterial blood
pressure followed by an increase in cardiac output. Oxytocin also
has a direct effect on the heart, causing decreased cardiac contrac-
tility and heart rate. If oxytocin is to be used, it should be given
by slow intravenous infusion. Ergometrine should also be avoided
in most cases as it can cause acute hypertension. The safety of
misoprostol is yet to be determined. Mechanical maneuvers to
reduce postpartum hemorrhage (bimanual compression, uterine
compression sutures, intrauterine balloons) are useful alterna-
tives. Careful hemodynamic monitoring postpartum is typically
required for 24–72 h, but this should be extended to 10–14 days
in cases of pulmonary hypertension. Multidisciplinary follow-up
should take place 6 weeks after delivery.
Expert commentary
The increase in maternal mortality associated with heart disease
in the UK is of obvious concern. Only by identifying why we
are seeing this rapid change in mortality rate will we be able to
reverse it. We must learn from the recent confidential enquiry.
www.expert-reviews.com
Review
Table 4. Chance of live birth in women with
cyanotic heart disease.
Factor Chance of live birth (%)
Maternal SaO2 (%)
>90 92
85–90 45
<85 12
Maternal Hb (g/dl)
<16 71
17–19 45
>20 8
Hb: Hemoglobin.
Data taken from [74].
Of the maternal deaths associated with heart disease two-thirds
of the women were overweight or obese. Care was considered
substandard in nearly half of the cases, to the degree that in two-
thirds of these cases the assessor thought that different care may
have prevented death. Increasing numbers of deaths are occurring
in women with acquired heart disease, not diagnosed prior to
pregnancy but with know risk factors. The presence of these risk
factors must be highlighted in the antenatal clinic. The occurrence
of cardiac symptoms (palpitations, chest pain, severe shortness of
breath) in these women should prompt early referral for investiga-
tion (ECG and echocardiography), promoting the timely diagnosis
of unsuspected cardiac disease in pregnant women. Women with
pre-existing heart disease should be assessed preconceptually and
risk factors for cardiac complications should be identified (prior
cardiac event, baseline NYHA class greater than II, cyanosis, left-
heart obstruction, reduced systemic left-ventricular function and
significant pulmonary regurgitation) [6] , and used to guide the
intensity of antenatal and postnatal care.
Five-year view
With initiatives such as the European Registry on Pregnancy and
Heart Disease and the UK obstetric surveillance system (UKOSS),
the next 5 years are likely to bring an improved knowledge of the
potential complications experienced by women during pregnancy
with pre-existing heart disease and their prognosis. Improvement
in the management of pregnancy complications will only be pos-
sible with our research efforts focused on understanding how heart
disease impacts on the cardiovascular physiological adaptations to
pregnancy and what the impact of pregnancy is on the natural his-
tory of the underlying heart condition. Combining the information
from the registry with the results of the basic physiological studies
will allow us to develop appropriate interventions, the benefit of
which can be tested in multicenter studies. Ultimately, we should
be capable of improving pregnancy outcomes for those with pre-
existing and acquired heart disease. Until then we must concen-
trate on raising the profession’s awareness of the possibility of heart
disease in pregnant women and promote management protocols
based on the best evidence ­currently available to us.
613
 Review Gelson & Johnson
Key issues
• Heart disease is the leading cause of maternal mortality in the UK.
• Ischemic heart disease is rapidly increasing in the pregnant population and is now the most common cause of cardiac death in
pregnancy in the UK.
• The congenital cardiac conditions of highest risk during pregnancy are pulmonary vascular disease, Marfan syndrome with a dilated
aortic root, left-sided obstructive lesions and a dilated poorly functioning left ventricle.
• Women with heart disease contemplating pregnancy should be assessed in a multidisciplinary prepregnancy clinic (staffed by an
obstetrician, cardiologist, anesthetist and midwife).
• Multidisciplinary input is required throughout the management of pregnancy.
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 CME Effect of maternal heart disease on pregnancy outcomes
Effect of maternal heart disease on pregnancy outcomes
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related, multiple-choice questions. To complete the questions and
earn continuing medical education (CME) credit, please go to www.
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1. A 27-year-old woman from the UK with congenital
heart disease is considering a first pregnancy. Which
of the following is the most accurate description of
her potential risks associated with pregnancy?
£ A Heart disease is the second leading cause of maternal
mortality in the UK
£ B The incidence of heart disease during pregnancy has
increased since 1990
£ C The severity of heart disease during pregnancy has
increased since 1990
£ D Acquired heart disease is more common than
congenital heart disease in pregnant women
2. Which of the following is the most common cause of
cardiac death during pregnancy in the UK?
£ A Ischemic heart disease
£ B Congestive heart failure
£ C Arrhythmias
£ D Dilated cardiomyopathy
3. A 34-year-old woman with congenital heart disease
is pregnant and has prior heart failure. She is a
baseline New York Heart Association class II patient
– with reduced systemic left ventricular function and
an ejection fraction of 35%. How many high risk
factors for maternal morbidity and mortality is she
likely to have?
£ A One
£ B Two
£ C Three
£ D Four
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licensed in the US who participate in this CME activity are eligible
for AMA PRA Category 1 Credits™. Through agreements that the
AMA has made with agencies in some countries, AMA PRA credit
is acceptable as evidence of participation in CME activities. If you
are not licensed in the US and want to obtain an AMA PRA CME
credit, please complete the questions online, print the certificate and
present it to your national medical association.
Activity Evaluation
Where 1 is strongly disagree and 5 is strongly agree
1 2 3 4 5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning
to occur.
3. The content learned from this activity will
impact my practice.
4. The activity was presented objectively and
free of commercial bias.
4. A 32-year-old woman considering pregnancy has a
mechanical heart valve. Which of the following
regimens for anticoagulation is likely to be associated
with the combination of lowest maternal and fetal
complications?
£ A Warfarin until week 35, then heparin until delivery
£ B Unfractionated heparin until week 13, then warfarin
until week 35, then heparin until delivery
£ C Low-molecular-weight heparin throughout pregnancy
£ D Unfractionated heparin throughout pregnancy
5. A 28-year-old woman with heart disease is
contemplating pregnancy. Which of the following is
likely to pose the highest mortality risk to her fetus?
£ A Use of statins during the third trimester
£ B Oxygen saturation below 85%
£ C Use of low-molecular-weight heparin
during pregnancy
£ D Maternal hemoglobin of 17 g/dl
617