1. family and parenting
2. motherhood
3. pregnancy

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20
Pregnancy and Heart Disease
Patrizia Presbitero, Giacomo G. Boccuzzi, Christianne J.M.
de Groot and Jolien W. Roos-Hesselink
Summary
Heart disease, though rare, can be present or discovered
during pregnancy because of haemodynamic overload
of the heart particulary during the third trimester when
cardiac output doubles.
Most of the knowledge in recognition and treatment
of cardiac disease during pregnancy is not based
on evidence from randomized trials, but is derived
from clinical experience, few case reports and small
consecutive series. These are summarized in the
guidelines on “Management of Cardiovascular
Diseases During Pregnancy” from the European
Society of Cardiology, the basis for this chapter. The
physiological changes that occur during pregnancy
have a different impact depending on the type and
severity of cardiac anomalies. Differential diagnosis
with normal pregnancy related physiological changes
is also discussed.
Particular emphasis is placed on early and accurate
diagnosis of congenital or acquired cardiac anomalies
Cardiovascular adaptations during normal
pregnancy
Pregnancy physiology is characterized by significant
haemodynamic changes that allow the uterus and developing fetus to receive an adequate blood supply. These
adaptations are well tolerated by the normal heart but
may result in haemodynamic problems for the diseased
heart. This implies that pregnancy may unmask previously silent heart disease.
Heart disease is present in 0.5–1% [1,2] of all pregnant
because often early intervention is essential for a safe
pregnancy and delivery.
Women at low risk are those in NYHA class I
or II with good ventricular function, without severe
left ventricular inflow or outflow obstruction or
pulmonary hypertension and who do not need to
take anticoagulants. Women at high risk are those
showing symptoms, of severe mitral or aortic stenosis
or unoperated coarctation, with cyanotic congenital
heart disease with or without pulmonary hypertension,
with impaired left ventricular function and/or
life-threatening arrhythmias. The same conditions
that endanger the mother also affect fetal survival.
Multiple therapeutic options including percutaneous
or surgical intervention are now available to allow for
a safe completion of the pregnancy. Management of
these patients requires teamwork from cardiologists,
obstetricians, anaesthetists, neonatologists and,
sometimes cardiac surgeons.
women and accounts for about 10–15% of all maternal
mortality [3]. Although the incidence of acquired disease has fallen (to below 0.2%) in Western countries
due to the reduction in the incidence of rheumatic
fever following the introduction of penicillin [1,2],
rheumatic heart disease is still the prevalent cause.
Congenital heart disease is becoming an increasing
problem during pregnancy as a result of the success of
neonatal corrective or palliative cardiac surgery. Because
of the increased delay to first pregnancy, maternal older
age and the increase in women’s smoking habits, symptomatic coronary disease, although rare, can occur and is
likely to increase.
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Chapter 20
Haemodynamic changes during pregnancy
The evaluation and management of heart disease in pregnant women require knowledge of the normal physiological changes associated with gestation, labour, delivery
and the early postpartum period (Fig. 20.1).
Blood volume and cardiac output
The most remarkable change related to pregnancy is the
increase in blood volume, which almost doubles by the
end of pregnancy. It starts to increase from the sixth
week, rising rapidly in the second trimester and becoming stable in the last 8 weeks [4]. Red cell mass increases
later in pregnancy but to a lesser extent than the plasma
volume, leading to slight haemodilution and the physiological anaemia of pregnancy, with haematocrit at about
33–34% and haemoglobin around 11–12 g/dl [5]. These
changes are more marked in twin or multiple pregnancies.
In the last trimester, peripheral arterial vasodilatation
may reduce arterial vascular filling and thereby induce
sodium and water retention mediated by aldosterone. In
an average pregnancy, there is a gradual accumulation of
500–900 mEq of sodium and total body water increases
by 6–8 litres, mostly extracellular. All these haemodynamic changes, which evolved to protect the mother from
blood loss at delivery, could play a role in the pathogenesis
of heart failure.
Cardiac output also increases to about 40% above the
non-pregnant value. Most of this increment is achieved
early in pregnancy, with peak values at 20–24 weeks [6].
This is achieved by an increase in stroke volume and
heart rate. In late pregnancy the increase in venous return
is sensitive to posture: a sharp drop in preload due to
inferior vena cava compression by the gravid uterus in
the supine position may cause hypotension, with weak-
50
Increase (%)
608
CO
40
30
SV
20
HR
10
0
0
5
8
12
16
20
24
28
32
36
38
Weeks
Figure 20.1 Increase in cardiac output (CO), stroke volume
(SV) and heart rate (HR) during pregnancy.
ness and light-headedness or syncope and even (short)
fetal distress. These symptoms are easily resolved by turning the woman from the supine to the lateral decubitus
position.
Heart rate
Heart rate starts to increase in the first weeks of pregnancy
and peaks in the first half of the third trimester. The
increase in resting heart rate averages 10–20 b.p.m. Atrial
tachyarrhythmias can be present in normal pregnancy
due to increased plasma catecholamine concentrations
and/or adrenoreceptor sensitivity, and to the stretched
atrial wall because of increased heart volumes [7].
Peripheral vascular resistance
Maternal peripheral and pulmonary vascular resistance
fall as a result of the low-resistance uteroplacental circulation, decreased mean aortic pressure and endogenous
hormones. Recently, there has been a focus on the role
of nitric oxide in the pathogenesis of vasodilatation [8].
Venous return increases, with a consequent rise in left
ventricular end-diastolic volume, although the filling
pressure does not rise because of ventricular structural
changes (increased compliance). In the first two trimesters,
the fall in systemic vascular resistance, which exceeds the
increase in cardiac output, leads to a drop in both systolic
and, especially, diastolic blood pressure, resulting in a
wide pulse pressure.
Labour, delivery and early postpartum period
The most dramatic swings in haemodynamic parameters
occur during labour, delivery and the immediate postpartum period. Uterine contractions significantly increase
venous return, and during a contraction cardiac output
may rise by a further 25%. Pain and anxiety cause an
increase in sympathetic tone during the second stage of
labour, which in turn enhances cardiac output and blood
pressure. These changes may be influenced by the type of
anaesthesia and analgesia used in labour and by the mode
of delivery [9]. Reduction of pain and apprehension can
be achieved by local and caudal anaesthesia. The patient
should be lying in the left lateral position during labour.
During the early postpartum period, cardiac output
increases as a result of a blood shift from the contracting
uterus to the systemic circulation and because of inferior
vena cava decompression (autotransfusion) [10]. There
are no haemodynamic differences between lactating
and non-lactating mothers. The cardiovascular adaptations associated with pregnancy regress by approximately
6 weeks after delivery.
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Pregnancy and Heart Disease
Cardiac evaluation in normal pregnancy
During pregnancy, cardiovascular disease or worsening
of a previous cardiac disease is difficult to detect: cardiopulmonary signs and symptoms typically reported during normal pregnancy may mimic heart disease. Fatigue
and decreased exercise capacity are common, along with
chest pain at rest that may be caused by oesophageal
reflux. As many as 75% of women may complain of mild
dyspnoea, whereas progressive orthopnoea or paroxysmal
nocturnal dyspnoea are rare. Palpitations are very common and are due to either a physiological increase in the
resting heart rate or atrial or ventricular ectopic beats [11]
(Table 20.1).
Physical examination
The physical examination of a healthy pregnant woman
shows a slightly fast resting heart, a bounding pulse,
a widened pulse pressure and warm flushed peripheries.
In addition, a slight elevation of venous pressure, the
presence of ‘tense’ soft tissues and peripheral oedema
(pedal oedema) are common.
The precordial impulse is hyperkinetic and the first
heart sound (S1) is increased, with prominent splitting
that may be misinterpreted as a fourth heart sound (S4) or
as a systolic click. During the later stages of pregnancy,
the physiological splitting of the second heart sound
(S2) may seem fixed. Third sound gallop (S3) is frequently
present by week 20 of gestation, whereas S4 is uncommon
and requires further evaluation.
Murmurs develop in nearly all women during pregnancy. They are usually soft, mid-systolic and heard at
the mid to upper left sternal border, and are secondary
to increased pulmonary blood flow. Benign murmurs
Table 20.1 Symptoms and signs during
pregnancy
include the continuous bruit resulting from increased
blood flow to the breasts, the ‘mammary soufflé’, and
the suprasternal venous hums, which can be obliterated
through ipsilateral jugular digital compression or by
firm pressure of the stethoscope. Diastolic murmurs are
unusual and therefore call for further evaluation. The
murmurs of stenotic heart valves (aortic stenosis, pulmonary stenosis, mitral stenosis) may increase in intensity because of the physiological increase in cardiac
output and fall in systemic vascular resistance. On
the other hand, the murmurs of incompetent heart
valves (aortic insufficiency, mitral insufficiency) may
decrease. Detection of murmurs as diastolic murmurs,
continuous murmurs and loud systolic murmurs equal
or greater than grade III in intensity cannot be considered physiological and hence need further careful
examination, starting with transthoracic echocardiography (Table 20.1) [12].
Additional diagnostic tools
Electrocardiogram
In normal pregnancy, there are non-characteristic electrocardiographic changes except for a slight leftward
shift of the electrical axis, which can give rise to a small Q
wave in lead III [13]. Severe left-axis deviation is not a
normal pregnancy variant and needs further evaluation.
Doppler echocardiography
Because of its safety and diagnostic power, Doppler
echocardiography is the first advisable diagnostic tool.
In a normal pregnancy, serial echocardiography usually
shows a significant increase in cardiac output, cardiac
index, left ventricular end-diastolic volume and left
ventricular wall thickness. An increase in left (up to 6%)
Normal pregnancy
Indicators of heart disease
Symptoms
Mild dyspnoea
Fatiguability
Decreased exercise tolerance
Rest chest pain
Palpitations
Severe or progressive dyspnoea
Paroxysmal nocturnal dyspnoea
Syncope with exertion
Effort or emotion chest pain
Signs
Pedal oedema
Warm extremities
Full, sharp and collapsing pulse
Prominent left ventricular impulse
Third heart sound (S3)
Grade 1–2 systolic ejection
murmurs
Premature beats
Continuous murmurs
Severe peripheral oedema
Clubbing and cyanosis
Persistent neck vein distension
Cardiomegaly
Fourth heart sound (S4)
Grade ≥ 3 systolic ejection
murmurs
Sustained arrhythmias
Diastolic murmurs
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Chapter 20
and right (up to 12%) ventricular diastolic dimensions is
present [14]. A mild increase in right atrial size (up to
20%) and transvalvular flow velocities and the presence
of mild atrioventricular valve regurgitation are normal
echocardiographic findings during pregnancy [15].
Chest radiography
Exposure to ionizing radiation should be avoided whenever possible, especially during early pregnancy since
malignancies and congenital abnormalities in offspring
have been described. Routine chest radiography (1.5 mGy)
exposes the uterus to a minimal (0.05 mGy) radiation
dose. Chest radiography should therefore be used only
if clinically indicated and performed with the minimum
amount of radiation, shielding the pelvic area. In addition, whenever possible it should be delayed until at least
the completion of the first trimester. In normal pregnancy,
the heart may appear enlarged due to the horizontal
position, and increased lung markings and small pleural
effusions can be detected [16].
Assessment of heart disease in pregnancy
The assessment of women with heart disease should
take place before conception in order to counsel them
adequately and to minimize maternal and fetal morbidity and mortality. The type and severity of cardiac
disease, general conditions, previous cardiovascular and
cerebral events, NYHA class, medications and obstetric
and family history should be taken into account in evaluating the risks and possibility of successful pregnancy. For
example, aortic insufficiency is normally well tolerated
during pregnancy because of the low peripheral resistance; however, if systemic hypertension, NYHA class III–
IV, an ejection fraction around 40% or ventricular arrhythmias are present, it becomes a high-risk condition.
Counselling, surveillance and treatment of women with
cardiac disease should be a collaborative effort including
obstetric, cardiological and anaesthesiological services.
The risk of recurrence in the offspring should be discussed. All patients with congenital heart diseases should
have informed genetic counselling before conception
(Table 20.2). An exercise test before pregnancy is very
important for evaluating functional capacity. The physiological changes of pregnancy are similar to the ones that
occur during exercise but over an extended period, so a
good exercise test will predict a well-tolerated pregnancy.
Echocardiography is required to assess cardiac haemodynamics, particularly pulmonary pressure, left ventricular
systolic function and severity of valve obstructions. When
the heart disease is severe (e.g. severe mitral stenosis),
balloon valvuloplasty or mitral valve surgery should
be considered before pregnancy. If a woman with heart
disease presents already pregnant, her cardiac status and
medication should be evaluated and should be treated
by a specialized team of cardiologist, obstetricians and
anaesthesiologist. A detailed plan for her pregnancy and
delivery should be made early in pregnancy and changed
if cardiac deterioration occurs.
Table 20.2 Recurrence risks of congenital heart disease in offspring*
Type of heart disease
Total risk (%)
Mother affected (%)
Father affected (%)
Acyanotic congenital heart disease
Atrial septal defect
Ventricular septal defect
Atrioventricular septal defect
Patent ductus arteriosus
Pulmonary stenosis
Left ventricular obstruction
Coarctation of aorta
3 –5
4 –8
10 –15
3–4
4
11–15
6
4.5– 6
6–9.5
7.5–15
4
6.5
10 –11
4
1.5
2–2.5
1–7
2
2
3
2.5
Cyanotic congenital heart disease
Tetralogy of Fallot
Transposition of great vessels
2.2–3.1
0.5
2.5
1.5
Mendelian disorders
Holt–Oram syndrome
Noonan’s syndrome
Marfan’s syndrome
50
50
50
50
50
50
50
50
50
*Based on multiple studies [36 – 40].
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Pregnancy and Heart Disease
Maternal low-risk conditions
All the conditions which benefit from the decrease in
systemic vascular resistance that occurs during pregnancy are very well tolerated regardless of their severity,
provided that left and right ventricular function is not
impaired. These conditions include mild and moderate
valve regurgitation [16,17] and small–moderate left-toright shunts without pulmonary hypertension.
Mild, moderate and moderately severe right ventricular outflow tract obstruction are very well tolerated
during pregnancy, as shown by previous series in which
no deaths and a low incidence of complications have
been reported [18]. However, the severe form of pulmonary valve stenosis and moderate stenosis with
impaired right ventricular function should be treated
before conception. Percutaneous pulmonary balloon
valvuloplasty during pregnancy may be indicated in very
severe (gradient suprasystemic) and/or symptomatic
cases. A few successful cases have been reported [16]
(Fig. 20.2). Stenting of pulmonary arteries can also be
performed successfully during pregnancy. Mild left ventricular outflow tract obstruction is well tolerated during
pregnancy even if pressure gradient doubles due to the
increased cardiac output (Fig. 20.3) [18], whereas the
moderate form must be followed carefully due to the possibility of rapid clinical deterioration. Aortic coarctation
carries a small risk of dissection [19] and should be corrected before pregnancy. During pregnancy women
with mild coarctation should undergo close monitoring
of blood pressure and treatment with a beta-blocking
agent will be indicated if hypertension develops [20].
Percutaneous balloon angioplasty should be avoided
in coarctation during pregnancy because of the risk of
aortic dissection or rupture [21]. Because of the risk
of restenosis after repair of coarctation in childhood, all
women with a history of operated coarctation who
consider pregnancy should be assessed.
In patients who have undergone previous successful
surgical repair without mechanical heart valve implantation (tetralogy of Fallot, atrial repair for transposition
of the great arteries [22], atrial and ventricular defects,
aortic coarctation [19,20]), pregnancy is well tolerated if
normal exercise tolerance, good functional status and
normal ventricular function are present. Close follow-up
is recommended (cardiac assessment every trimester).
Although women with some conditions are at low
risk during pregnancy, other conditions can worsen
after delivery, including intra-atrial repair of transposition of the great arteries [22,23], Ebstein’s anomaly
[24], mild valve stenosis and mild cardiomyopathies
(ejection fraction 45–55%). For example, 25% of women
with intra-atrial repair of transposition experience deterioration of their right ventricular function during pregnancy and most of them do not recover to the baseline
level [25].
Figure 20.2 (A,B) Echocardiographic (A, parasternal short-axis view; B, continous-wave Doppler) and (C) angiographic image of
a pregnant woman with severe pulmonic stenosis. Peak gradient was 144 mmHg. She was treated with balloon dilatation during
pregnancy (D), the peak gradient decreasing to 40 mmHg after dilatation (E). RV, right ventricle; LV, left ventricle; PA, pulmonary
artery; Vmax, maximal velocity (m/s) measured over the pulmonic valve.
(Continued p. 612)
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Chapter 20
C
D
E
Figure 20.2 (cont’d ).
Maternal high-risk conditions
Previous studies have recognized that prior cardiac events
or arrhythmias, poor functional class, cyanosis, left heart
obstruction and left ventricular systolic dysfunction independently predict maternal cardiac complications [26,27].
There are some specific conditions at particular risk
during pregnancy.
Pulmonary hypertension
A 30–50% maternal mortality risk is still reported in
patients with severe pulmonary vascular disease, either
with septal defects (Eisenmenger’s syndrome) or without [28,29], and fetal loss is of a similar magnitude.
Systemic vasodilatation increases the right-to-left shunt
and decreases pulmonary output, leading to a low-output
status. Death occurs in the last months of pregnancy or
in the first few days after delivery because of pulmon-
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Pregnancy and Heart Disease
613
A
B
Figure 20.3 Echocardiographic
continous-wave Doppler images of a
severe aortic stenosis in a pregnant
woman. The peak gradient changed
from 45 mmHg before pregnancy (A) to
85 mmHg after 18 weeks of pregnancy (B).
ary hypertensive crises, mostly due to fibrinoid necrosis,
rarely to pulmonary thrombosis. It can happen even in
patients with little or no disability before or during pregnancy. The level of pulmonary hypertension that should
be considered at risk is around 70 mmHg systolic or
> 30 mmHg mean pulmonary pressure. Even moderate
forms of pulmonary vascular disease can worsen during
pregnancy as a result of the decrease in systemic resistance and of overload of the right ventricle. Termination of
pregnancy is advisable. If pregnancy continues, patients
should restrict their physical activity, avoid the supine
position and take subcutaneous heparin as prophylaxis
against thromboembolism [17,30]. Intravenous or pulmonary infusion of prostacyclin (epoprostenol) has been
occasionally used to decrease pulmonary pressure during delivery and postpartum in order to manage pulmonary hypertensive crises [31,32]. Further evaluation
is needed before using new drugs such as the oral phosphodiesterase inhibitor sildenafil and the endothelin
receptor antagonist bosentan during pregnancy [33,34].
Invasive monitoring during labour and delivery is
recommended.
Severe left ventricular tract obstruction
Congenital, most often bicuspid, aortic valve stenosis
is rare during pregnancy because patients have usually
had percutaneous or surgical valvuloplasty in childhood
or before conception. Women with an aortic valve area
< 1.0 cm2 should be discouraged from conceiving before
treatment especially when they are symptomatic. In
severe aortic stenosis, the fixed resistance may not be
able to accommodate the increased cardiac output that
occurs during pregnancy. An increase in both gradient
and left ventricular end-diastolic pressure is induced and
can cause heart failure, low output and reduction in
uteroplacental perfusion. Important ECG changes of left
ventricular overload in a previously normal ECG, signs of
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Chapter 20
A
B
PREGNANCY IN CYANOTIC CHD
Logistic regression analysis of risk factors determinant for
fetal survival
RISK FACTORS
Maternal disease
Hb
O2 saturation
Age
Aortic insufficiency
Previous shunt
PREDICTIVE POWER
+
+
+
–
–
+
P-VALUE
0.002
<0.0001
0.0001
0.74
0.02
0.16
100
Fetal survival (%)
614
80
60
40
20
0
<85%
85–90%
>90%
Oxygen saturation (%)
Figure 20.4 Risk factors affecting fetal survival: (A) multiple regression analysis shows that maternal disease, haemoglobin and
oxygen saturation are significantly related to fetal survival; (B) fetal survival declines with the decrease in maternal oxygen saturation.
heart failure and low systemic blood pressure can appear.
The clinical symptoms occur at 20–24 weeks of gestation.
Previous series which reported high mortality in aortic
stenosis [35] were probably due to the underestimation
of these signs during pregnancy as well as the lack of
immediate intervention. If the fetus is viable (> 34 weeks)
delivery is advised, thus restoring the pre-pregnancy
haemodynamic status. If the valve is not heavily calcified
and no regurgitation is present, percutaneous balloon
valvotomy can be successfully performed. Five cases
have been reported, with significant reduction of valve
gradient, enabling the pregnancy to continue [21,36].
Surgery can be an alternative [37]. Most recent series [38]
of pregnancy in aortic stenosis reported no deaths but
some complications, such as pulmonary oedema and further valve deterioration requiring surgery.
Cyanotic heart disease without pulmonary
hypertension
Cyanotic congenital heart diseases are usually corrected
before pregnancy, but some inoperable or palliated cases
can reach child-bearing age. The degree of maternal hypoxaemia is the most important predictor of maternal and
fetal outcome (Fig. 20.4). With resting maternal blood
saturation below 85%, maternal mortality is 2–5%,
fetal loss is 85% and premature delivery or a low-birthweight neonate is around 50%; pregnancy should therefore be discouraged [39]. Maternal complications (heart
failure, pulmonary or systemic thrombosis, supraventricular arrhythmias) occur in 30% of cases. Low-dose
heparin prophylaxis is widely used and recommended,
although its value has not been proved. If oxygen saturation is 85–92%, it is advisable to measure it during exercise. If there is a sudden and important drop in oxygen
saturation during exercise, the pregnancy has a poor
prognosis and should be discouraged.
Tetralogy of Fallot is the most common cyanotic
80
72
70
Unoperated or palliated
Radical correction
60
50
42
40
31
30
20
10
8,6
2
2
8 7,4
0
Maternal
mortality
Live born
Maternal
complications
Offspring
cardial
defect
Figure 20.5 Maternal and fetal complications in cyanotic
patients (mostly tetralogy of Fallot) selected to receive either
no operation/palliation or radical correction. Maternal
complications decreased and live births increased substantially
with radical correction.
congenital heart defect. Comparing fetal and maternal
outcome in uncorrected (i.e. cyanotic) and corrected
tetralogy of Fallot, it is evident that persistent cyanosis is
the most important determinant of maternal and fetal
outcome (Fig. 20.5). Offspring of mothers with tetralogy
of Fallot regardless of correction carry a risk of having
congenital heart disease (3–10%) (see Table 20.2).
Impaired left ventricular function
Besides basic cardiac disease, left ventricular function is
one of the main determinants of maternal and neonatal
outcome. No reviews are available that indicate a cut-off
value for left ventricular ejection fraction below which
pregnancy is contraindicated. An echocardiographic ejection fraction > 40% with a good rise in systemic arterial
pressure on exercise testing allows the continuation of
pregnancy, although complications can still occur. Pregnancy termination should be advised if ejection fraction is
below 40% with increased left ventricular dimensions [17].
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Pregnancy and Heart Disease
During pregnancy, restriction of physical activity and
serial echocardiogram evaluation should be performed.
Particular attention should be focused on the recognition of ventricular arrhythmias during pregnancy and
after delivery, in which case 24-h Holter registration
should be indicated. Particular attention should be paid
when valvular disease with impaired ventricular function is present because the prognosis can be worse.
Fetal high-risk conditions
The fetal risks are as follows.
1 The recurrence risk of congenital malformations in
the offspring of patients with major heart defects
(see Table 20.2) ranges from 2 to 50% depending on
the type of parental disease, with an excess in the
offspring of affected women [17,40–44]. Fetal
echocardiography can detect the presence of
congenital heart disease and should be performed if
the mother or father has congenital heart disease.
2 Abortion.
3 Intrauterine growth retardation.
4 Prematurity (Fig. 20.6).
The last three complications depend on type and severity
of maternal disease and poor maternal functional class
(NYHA > II) [25]. Additional risk factors for adverse fetal/
neonatal events, besides the conventional obstetric ones
(history of premature delivery or rupture of membranes,
incompetent cervix, or caesarean section; intrauterine
growth retardation, antepartum bleeding > 12 weeks’
gestation, febrile illness, or uterine/placental abnormalit-
ies during present pregnancy), include maternal age > 35,
multiple gestation, smoking during pregnancy and anticoagulation therapy [45]. Besides cyanotic heart disease,
another condition that carries an adverse fetal outcome
(45% fetal survival) is the Fontan repair for tricuspid
atresia or single ventricle. In this condition the venous
congestion that occurs during pregnancy leads to congestion of the intrauterine veins, with a very high incidence of spontaneous abortion. Nowadays conversion
from classic Fontan to total cavopulmonary connection
should be considered before pregnancy. We have to
emphasize that the prematurity associated with poor
maternal condition carries a high risk of newborn disabilities: 30% when the fetus is delivered at 27 weeks,
60% at 24 weeks [43].
Specific conditions
Mitral valve stenosis
Although its incidence is decreasing in Europe, rheumatic
heart disease is still responsible for most of the cardiac
complications during pregnancy. Mitral valve stenosis,
nearly always of rheumatic origin, is the most common
(90%) and important cardiac valvular problem during
pregnancy. Mortality among pregnant women with
minimal symptoms is less than 1% but in severe disease
can reach 5%. Labour, delivery and the immediate puerperium appear to be the periods most at risk [17,46–48].
The pressure gradient across the narrowed mitral
valve may increase greatly during pregnancy because of
Figure 20.6 Creation of an atrial septal defect in utero for fetus with hypoplastic left heart syndrome and intact atrial septum.
Transabdominal ultrasound image of the heart in a fetus with dilated left atrium and thin bulging atrial septum before atrial septal
puncture (A), during septal puncture with Chuba needle (B) and during dilatation with 3-mm coronary angloplasty balloon (C). With
permission of James E. Lock Circulation (2004) 110: 253–258.
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the physiological increase in heart rate (decreasing left
ventricular diastolic filling time) and cardiac output. This
can lead to a rise in left atrial and pulmonary wedge pressures and inability of cardiac output to increase appropriately with exercise. The onset of clinical symptoms
(excessive fatigue, breathlessness on exertion, orthopnoea
and nocturnal dyspnoea) may occur even in women
with moderate valve stenosis or who were previously
symptom-free, usually in the middle trimester. Development of atrial fibrillation could further aggravate the clinical status, leading to acute pulmonary oedema.
Predictors of adverse maternal outcomes include
degree of mitral valve stenosis (valve area < 1.5 cm2),
NYHA functional class II or more before pregnancy
and history of cardiac events [25,45]. Patients with
mild valve stenosis (valve area > 1.5 cm2) who are either
asymptomatic or have minor symptoms can almost
always be managed with behavioural advice (restriction
of salt intake, reduction of physical activity up to complete bed rest) and judicious medical therapy (diuretics to
reduce pulmonary and venous congestion; beta-blockers
to reduce heart rate and increase diastolic filling period).
The onset of tachyarrhythmias such as atrial fibrillation or supraventricular tachycardia requires immediate
treatment with cardioversion. Anticoagulation therapy
is indicated in patients with atrial fibrillation. In patients
with moderate mitral valve stenosis (valve area 1.1–
1.5 cm2), the different therapeutic strategies depend on
the severity of symptoms before and during pregnancy
and the rise in pulmonary pressure: patients who are
either asymptomatic or mildly symptomatic (NYHA I–II)
should undergo close follow-up with serial echocardiographic assessment (measurement of mean transmitral
gradient and pulmonary artery pressure) and clinical
evaluation; percutaneous balloon valvuloplasty or valve
repair/replacement during pregnancy should be considered in cases with persistent symptoms despite optimal
medical therapy. In patients with severe mitral valve
stenosis (valve area < 1 cm2), percutaneous balloon
valvuloplasty or surgical intervention before conception
is indicated. In pregnant women, careful monitoring and
performance of these procedures at the right time have to
be planned.
Percutaneous balloon valvuloplasty has been shown
to be a successful and safe procedure during pregnancy
in experienced centres, and has become the first-choice
interventional treatment in anatomically suitable valves
(young patients with non-calcified pliable valves without
too much subvalvular thickening or significant mitral
regurgitation) are present as a result of the significant
reduction in fetal and neonatal mortality [21,49].
Labour and delivery should be planned carefully.
Effective anaesthesia to minimize pain and anxiety, in
addition to shortening of the second stage of labour, will
decrease the haemodynamic demand on the maternal
heart. Bedside ECG monitoring should be used to document rhythm disturbances. Swan–Ganz catheters are
frequently used in moderate and severe mitral stenosis to
monitor fluid balance. The safety of breast-feeding depends
on the mother’s medication in the postpartum period.
Hypertrophic cardiomyopathy
Although symptoms, particularly chest pain, may increase, pregnancy is generally well tolerated and absolute
maternal mortality is very low and mostly limited to
high-risk patients [50,51]. Management of hypertrophic
cardiomyopathy during pregnancy should not differ
from that outside pregnancy. No treatment other than
reassurance should be indicated in asymptomatic or mild
symptomatic women, whereas in symptomatic patients
beta-blockers and low-dose diuretic therapy may be
indicated. Because of the negative impact of tachycardia,
if supraventricular arrhythmias develop, rate-control
therapy and prompt electrical cardioversion are needed.
Normal vaginal delivery is safe but careful monitoring of
blood loss is needed [50].
Prosthetic heart valves
In women of child-bearing age, surgical valve repair is
always preferable to replacement and must be performed
whenever possible. If valve replacement is needed, the
decision about the best type of valve prosthesis to use
should take into account the woman’s age (in very young
women rapid tissue valve degeneration is common), the
presence of other conditions such as atrial fibrillation
requiring anticoagulant therapy, and the risk of reoperation (complex anatomy, re-repeat). Bioprosthetic valve
appears to be the best choice provided that the woman is
informed about the structural valve deterioration associated with pregnancy and the inevitability and risk of
reoperation. Previous studies have shown that pregnancy is associated with an accelerated rate of structural
valve deterioration (12–60%) [49,54,55]. The incidence
of prosthetic valve reoperation is 60–80% at 5–10 years
follow-up, and the mortality of reoperation is 2–3.8%
[54]. The management of women with bioprosthetic
valves should include serial clinical evaluation and twodimensional echocardiography for early detection of
valve structural deterioration, and antibiotic prophylaxis
at delivery.
In women with mechanical valves, pregnancy is associated with a 10% risk of prosthetic valve thrombosis
and/or systemic embolization, necessitating the use of
some form of anticoagulation during pregnancy throughout pregnancy. On the other hand, the use of warfarin,
particularly between weeks 6 and 12 of pregnancy, is
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Pregnancy and Heart Disease
Table 20.3 Risks of anticoagulant treatment during pregnancy reported in the literature series
Fetal risk
Death
Embryopathy
Maternal risk
Death
Thromboembolism
Warfarin
Heparin (in first
trimester)
Heparin throughout
pregnancy
Low molecular
weight heparinH
30%
4–10%
24%
2%
–
–
?
?
1.8%
3.9%
4.2%
9–24%
7%
25%
?
?
associated with fetal embryopathy (nasal hypoplasia,
bone stippling and optic atrophy) that occurs in approximately 6% of cases and an increased risk of miscarriage
or stillbirth (cerebral fetal haemorrhage). Because of this
maternal and fetal ‘double jeopardy’, women with
mechanical valves should be informed about the risks of
pregnancy and the necessity for immediate pregnancy
testing if menstrual periods are missed.
The most appropriate anticoagulation regimen will be
based on several factors: type of valve prosthesis (e.g. old
generation caged-ball prosthesis vs. new bileaflet tilting
disc), valve position (mitral vs. aortic), warfarin dose and
the desires of prospective parents. Low-risk patients are
those with an aortic new-generation valve prosthesis or
those who need low doses of warfarin (≤ 5 mg) to maintain an adequate international normalized ratio (INR).
The risks of anticoagulant treatment (Table 20.3) always
have to be discussed with the mother.
As a result of the controversial recommendations of
the cardiology societies about the use of low-molecularweight heparin (LMWH), there is no consensus of opinion [47,52–57]. The management options, which await
confirmation, include the following.
1 Heparin and warfarin combination: stop warfarin
treatment as soon as the pregnancy test is positive.
Unfractioned heparin in the first 13 weeks of
pregnancy, switching to warfarin in the second
trimester, continuing it until week 36 of gestation or
2 days before the planned delivery and then changing
again to heparin until 4 –5 days after delivery.
Heparin should be terminated at the onset of labour
and re-instituted shortly (12–24 h) after delivery.
During pregnancy heparin should be given
subcutaneously two or three times daily and the dose
adjusted to maintain the partial thromboplastin time
at greater than twice control levels at all times; the
monitoring should be performed at least twice weekly.
In clinical practice this option is rarely chosen.
2 LMWH and warfarin combination: stop warfarin
treatment as soon as the pregnancy test is positive.
LMWH (nadroparin calcium or enoxaparin) in the
first 13 weeks of pregnancy, switching to warfarin in
the second trimester, continuing it until week 36 of
gestation or 2 days before the planned delivery and
then changing to heparin. LMWH should be given
subcutaneously twice daily and the dose adjusted to
body weight to maintain anti-Xa between 0.5 and
1.0 U/ml 4–6 h after injection. LMWH does not cross
the placenta. Meticulous attention should be paid
when shifting from one regimen to the other because
most of the complications reported occur during
these periods. These therapy changes are best
followed with a hospitalized regimen. This option
is probably best in high risk patients.
3 Warfarin throughout the whole of pregnancy if low
doses are needed to maintain appropriate INR, with
patients’ consensus.
4 LMWH throughout the whole of pregnancy,
administered twice daily with dose adjusted to body
weight. (This option awaits confirmation and should
therefore be considered only in low-risk patients.)
Marfan’s syndrome
With a population incidence of 1 in 5000, Marfan’s
syndrome is the most frequently encountered fibrillin-1
deficiency disorder. It is transmitted as an autosomal
dominant trait and is characterized by multiorgan dysfunction, predominantly affecting the eyes, skeleton and
cardiovascular system. There are two main problems in a
woman with Marfan’s syndrome who is contemplating
pregnancy: (1) the risk of serious maternal complications
during or shortly after pregnancy and (2) the risk of
recurrence in offspring.
Whenever possible before starting pregnancy, any
woman with Marfan’s syndrome should undergo a full
clinical assessment (family history, ultrasound examination of the entire aorta, echocardiography, magnetic
resonance imaging) and a careful counselling of maternal
and fetal risk. The risk of aortic dissection or other serious
cardiovascular complication (endocarditis or congestive
heart failure) during pregnancy is 1% even in the absence
of aortic root dilatation, and may further increase, reaching
10%, in the presence of poor family history, aortic root
diameter > 45 mm and significant mitral or aortic valve
regurgitation [25,58]. The recommendations are as follows.
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1 Patients with aortic root enlargement > 4.5–5 cm
and aortic or mitral severe regurgitation should
undergo elective surgery before pregnancy; if they
refuse, they will be advised against pregnancy.
2 In patients with aortic root enlargement of 4–4.5 cm,
aortic root dimension assessment with serial
echocardiography (each trimester until 6 months
after delivery) should be recommended. During
pregnancy, physical activity should be limited and
the use of beta-blocker therapy is recommended.
3 Even in patients without cardiovascular involvement,
the relatively ‘small’ risk of complications should be
discussed, as these can occur outside pregnancy.
Clinical and echocardiographic monitoring should
be performed during pregnancy and normal vaginal
delivery should be conducted.
Besides the risk of cardiovascular involvement, women
with Marfan’s syndrome must know and accept that there
is a 50% risk of their offspring having Marfan’s and that
the degree of severity of the disease could be worse than
that of the parent.
Coronary heart disease
Acute myocardial infarction rarely occurs in women of
child-bearing age and has been estimated to occur in
only 1 in 10 000 women during pregnancy [59]. However, with the current trend of child-bearing at an older
age and the ongoing effects of cigarette smoking, diabetes and stress, the occurrence of acute myocardial
infarction during pregnancy can be expected to increase.
Myocardial infarction occurs mostly in multiple pregnancies and most commonly in the anterior wall. The
reported maternal mortality rate, before the current practice of primary percutaneous coronary angioplasty, varies
from 21 to 48%, either at the time of infarction (mostly
in the third trimester) or within 2 weeks of the infarction
[59,60]. The differential diagnosis of ischaemic chest
pain includes haemorrhage, sickle crises, pre-eclampsia,
acute pulmonary embolism and aortic dissection [61]. It
is confirmed by ECG changes and increase in enzyme
levels. Management includes coronary angiography with
abdominal shielding. Spontaneous coronary dissection
of the proximal left anterior coronary artery is the most
common cause of myocardial infarction, especially in the
postpartum period. Successful treatment includes coronary stenting, emergency coronary artery bypass grafting
or administration of tissue plasminogen activator, as
described in case reports [62].
The delivery should be postponed for at least 2 or
3 weeks after the myocardial infarction to allow adequate
healing. The mode of delivery should be determined by
obstetric reasons and the clinical status of the mother.
Cardiac transplantation
If ventricular function is normal and there are no signs
of rejection, pregnancy is usually successful. The absence
of rejection should be established before conception and
needs to be assessed during pregnancy. Preconceptional
genetic counselling is necessary depending on the indication for transplantation, such as mitochondrial myopathy
or familial dilated cardiomyopathy. Management during
pregnancy includes monitoring left ventricular function
and preventing complications such as hypertension,
infection, preterm labour, intrauterine growth restriction and pre-eclampsia [61,63,64]. The choice of delivery
mode is based on obstetric indications.
Cardiovascular treatment during pregnancy
Treatment in pregnancy is not based on randomized
trials but on limited data from case reports (successes
tend to be reported), observational studies and clinical
individual experience. The safety of both mother and
fetus has to be taken into account because treatment
for one can have adverse effects on the other. Pregnant
patients with heart disease and their close relatives
should receive general advice such as limitation of physical activity, with complete bed rest in severe cases, and
salt and fluid restriction. Self-weighing should be encouraged and in the case of sudden unexpected weight
gain the physician should be contacted. Other general
advice includes stopping smoking and avoiding excessive alcohol intake and all unnecessary medications.
Pharmacological therapy
The use of any medication in pregnancy and during
lactation has to consider the safety and tolerability for
the fetus and infant, the physiological maternal changes
and the risk–benefit ratio. In patients who are already
taking cardiovascular medications, discontinuation or
the switch to a ‘safer’ drug should be discussed before
conception. Because of the lack of randomized trials and
the fear of tragedies such as the thalidomide disaster,
there is an extreme reluctance to introduce any new
drugs in pregnancy. Drugs with the longest record of
safety should be used as the first-choice therapy [65,66].
However, the fear of ‘unpredictable’ complications must
not overcome the correct use of drug treatment in pregnancy, because most of the drugs used to treat heart
disease can be prescribed safely during pregnancy.
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Pregnancy and Heart Disease
The effective plasma concentration of drugs varies during pregnancy. For example, the progesterone-induced
reduction in gastrointestinal motility and the estrogeninduced increase in gastric secretion may result in altered
drug absorption. Intravascular volume is increased during
pregnancy, resulting in enhanced volume distribution and
lower serum concentrations that may require an increase
in the loading dose. Serum protein concentration falls
during pregnancy, causing a reduction in protein binding and an increase in the non-protein-bound fraction.
Increases in renal blood flow and glomerular filtration rate
may augment drug clearance. The transplacental transfer
of drugs depends on liposolubility or hydrosolubility and
molecular weight of the drug, the pH of maternal and
fetal fluids, the link with carrier protein and the gradient
between maternal and fetal concentration [67,68].
Table 20.4 categorizes drugs according to the reliability of evidence of fetal risk and the potential risk–benefit
ratio [65–81].
Therapy of heart failure
Diuretics are the first drugs to be employed in order to
reduce hypervolaemia in patients with severe symptomatic congestive heart failure not responding to water and
salt restriction. Diuretics are not recommended for management of pedal oedema or prophylaxis of eclampsia. In
patients already receiving diuretics, the therapy should
be continued during pregnancy and the peripartum
period independently of the presence of mild hypotension. Although furosemide crosses the placental barrier,
it is the drug of choice because no teratogenic or cardiovascular fetal effects have been described. Collateral
effects to be controlled are hypovolaemia and hypokalaemia. Particular caution should be taken in cyanotic
patients because haemoconcentration can cause thrombosis. No adverse events have been reported in patients
treated with spironolactone, particularly indicated in cases
of hypokalaemia. Thiazides are not recommended due
to the reported neonatal thrombocytopenia, jaundice,
hyponatraemia and bradycardia [67,68].
Angiotensin-converting enzyme (ACE) inhibitors
should be withdrawn during pregnancy because of teratogenic effects. Reported complications include fetal and
neonatal renal failure, oligohydramnios, intrauterine
growth retardation and hypoplasia of skull bones especially in the second and third trimester [69]. There are no
data available about angiotensin II receptor antagonists
in pregnancy, but because their actions are similar to
those of ACE inhibitors their use is contraindicated.
Specific information on the safety of nitrates and
sodium nitroprusside is lacking. Intravenous as well as
oral nitrates have been used in a few patients for the
treatment of hypertension, myocardial ischaemia and
heart failure, although case reports of fetal heart decelerations have been reported.
Dopamine and dobutamine can be used in low-output
congestive heart failure. A few cases have been reported
with no adverse effect [67–69]. However, during pregnancy with a viable fetus, fetal monitoring is advisable.
The experience with digoxin is extensive and there are
no reports of teratogenicity associated with its use. It is
considered a preferred choice for treatment of congestive
heart failure, especially when supraventricular arrhythmias and systolic dysfunction are present. Furthermore,
digoxin is the first-line drug for maternal and fetal rate
control in atrial fibrillation/flutter and for the treatment
of fetal supraventricular tachycardias [70,71]. Because
of increased renal clearance, the serum digoxin concentration may be lower and so maternal dose should be
increased. In the presence of decreased renal function
or concomitant administration of amiodarone, maintenance doses may require reduction. Even if higher doses
are required during pregnancy, caution in changing the
amount of digitalis is advised because digitalis toxicity
has been associated with miscarriage and fetal death. In
the third trimester, serum digoxin levels may appear
falsely elevated because of the presence of digoxin-like
substances interfering with radioimmunoassays. Hence,
the monitoring of digoxin levels would not be helpful in
guiding treatment [71].
Management of arrhythmias
Pregnancy may increase the incidence of arrhythmias.
Knowledge of the underlying heart disease is important
for the correct treatment. Most of the antiarrhythmic
drugs can be prescribed safely in pregnancy but an attempt
to recognize a correctable cause should be undertaken
before starting therapy. All antiarrhythmic drugs cross
the placental barrier and their potentially toxic effect on
the fetus should be taken into consideration, particularly
during the first weeks of pregnancy [71].
maternal tachyarrhythmias
Ectopic beats are present in one-third of pregnant women
but are generally benign and well tolerated. No treatment
other than reassurance and correction/elimination of
potential stimulants are indicated. An increased risk of
new-onset, and exacerbation of, supraventricular tachycardia during pregnancy has been reported (3%), while
ventricular tachycardia is rare. When dysrhythmias such
as atrial fibrillation or flutter are present during pregnancy, an underlying cause should be considered.
Electrical cardioversion is the treatment of choice
for all drug-refractory maternal arrhythmias or those
619
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Chapter 20
Table 20.4 Cardiovascular drugs during pregnancy*
Drug
Use during pregnancy
Antiarrhythmic agents
Adenosine
First-line treatment: paroxysmal
supraventricular tachycardia
Amiodarone
Refractory maternal and fetal arrhythmias
Maternal arrhythmias in presence of
impaired left ventricular function
Beta-blockers
Control ventricular rate in atrial
(atenolol,
fibrillation
propranolol,
Second-line treatment of maternal
metoprolol)
supraventricular arrhythmias
Prophylactic therapy for supraventricular
and ventricular tachycardias
Digoxin (see heart failure)
Flecainide
Second-line therapy for maternal and
fetal supraventricular arrhythmias
Lidocaine
Maternal ventricular arrhythmias
Local anaesthesia
Propafenone
Second-line therapy for maternal
supraventricular arrhythmias
Sotalol
Second-line therapy for maternal
supraventricular arrhythmias
Fetal tachycardia
Verapamil
Second-line therapy for maternal
supraventricular arrhythmias
Heart failure therapy
ACE inhibitors
Not recommended
Angiotensin II
Not recommended
receptor
antagonists
Digoxin
Prophylactic therapy for supraventricular
tachycardias
Control of ventricular rate in atrial
fibrillation
Fetal tachycardia
Heart failure
Loop diuretics
Severe symptomatic congestive heart
(furosemide)
failure
Sparing diuretics
Congestive heart failure and
(spironolactone)
hypokalaemia
Nitrates
Myocardial ischaemia
Heart failure
Hypertension
Hypertensive disease therapy
Prophylactic treatment in women with historical risk factors
Aspirin
Reduces the risk of perinatal death and
pre-eclampsia
Calcium
Positive impact on maternal and fetal
supplementation
morbidity needs to be confirmed
Magnesium sulphate Reduces the risk of eclampsia in women
with severe pre-eclampsia
Severe hypertension
Hydralazine
Labetalol
Nifedipine
Nitroprusside
Second-line therapy
First-line therapy
First-line therapy
Second-line therapy
*Based on multiple studies [57–73].
Adverse fetal or neonatal effects
Breast-feeding
No teratogenicity or other adverse
effects
Intrauterine growth retardation,
premature birth, fetal
hypothyroidism
No teratogenicity
Fetal bradycardia, hypoglycaemia,
premature labour and
metabolic abnormalities
Intrauterine growth retardation?
Short half-life makes a
problem unlikely
Secreted in maternal milk
so not recommended
No reports of teratogenicity
Limited data
Fetal bradycardia, central nervous
system toxicity
Limited data
Compatible
Limited data
Fetal bradycardia, intrauterine
growth retardation
Limited data
Maternal hypotension and
subsequent fetal hypoperfusion
Limited data
Teratogenic effects
Limited data
Compatible
Limited data
No reports of teratogenicity
Compatible
No teratogenic or cardiovascular
fetal effects
No teratogenic effects
Compatible
Fetal heart deceleration, maternal
hypotension and subsequent
fetal hypoperfusion
Limited data
Compatible
Haemorrhage, prolongation of
labour
Limited data
Limited data
Neonatal bradycardia
Neonatal bradycardia
Fetal distress
Thiocyanate poisoning
Compatible
Limited data
Limited data
Limited data
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Pregnancy and Heart Disease
causing haemodynamic compromise and can be performed safely at any time during pregnancy. Paroxysmal
supraventricular tachycardias are usually well tolerated
and require active therapy only if very frequent or
long-lasting or with haemodynamic instability. Vagal
manoeuvre should be tried first and, if ineffective, intravenous adenosine would be the first-choice drug.
Maternal effects may include facial flushing, headache,
dyspnoea and nausea. Adenosine crosses the placenta
but no adverse fetal effects have been described. Secondline drugs include beta-blocking agents or propafenone.
Intravenous verapamil can be used but maternal hypotension, heart failure and inhibition of labour have been
reported. If prophylactic drug therapy is needed, then β1
receptor blockers or digoxin are the first choice [69,70].
Atrial fibrillation and flutter are rare in pregnancy and
often secondary to congenital or valvular heart disease.
Therapy includes ventricular rate control using digoxin
or beta-blocking agents and conversion to sinus rhythm
using propafenone or amiodarone (termination of atrial
episodes should be attempted in order to avoid anticoagulation therapy). Ventricular tachycardia during
pregnancy is rare in healthy women without organic disease but it can occur when ventricular scars are present
(e.g. tetralogy of Fallot). Beta-blockers are the first-line
therapy when ventricular function is preserved. Some
forms of non-sustained ventricular tachycardia in normal
hearts respond well to verapamil. If ventricular function
is impaired, amiodarone is the only option. Chronic administration of amiodarone can have adverse effects on
the mother in 3–5% of cases, including thyroid malfunction, photosensitivity and corneal deposition. In the fetus,
long-term treatment with amiodarone can cause neonatal
hypothyroidism [71,72], which is however reversible.
Although catheter ablation has been performed in
a pregnant patient, it should be recommended only in
patients with drug-refractory, poorly tolerated or lifethreatening arrhythmias [68]. The presence of an implantable cardioverter–defibrillator should not be considered a
contraindication to pregnancy [73], but implantation during pregnancy has never been reported in the literature.
maternal bradyarrhythmias
Compared with the tachyarrhythmias, bradyarrhythmias
are uncommon, but when they occur are usually well
tolerated. Management should not be influenced by pregnancy. Temporary or permanent pacemaker, if required,
can be implanted at any stage of pregnancy, although
treatment is generally not indicated unless the conduction abnormality causes symptoms. Women with congenital complete heart block, as previously reported, can
accomplish an uneventful and successful pregnancy [74]
with or without a pacemaker.
fetal arrhythmias
Fetal tachycardia, defined as a heart rate greater than
180 b.p.m., is a condition that occurs in approximately
0.4–0.6% of all pregnancies, and may cause non-immune
fetal hydrops and lead to fetal morbidity and mortality.
Maternal full-dose digoxin is the first-line antiarrhythmic
agent in non-hydropic fetuses, while verapamil and
beta-blocking agents are second-line therapy. In drugrefractory fetal tachycardia, particularly if accompanied
by hydrops fetalis or ventricular dysfunction, amiodarone
represents a safe and effective option [75]. Sotalol should
be considered a valuable treatment option for fetal atrial
fibrillation, which is extremely rare [76].
Prophylaxis of endocarditis
As in the non-pregnant state, antibiotic prophylaxis is
indicated before undergoing a procedure likely to cause
bacteraemia. Since the incidence of bacteraemia following vaginal delivery has been reported to be low (0–5%),
routine antibiotic prophylaxis for uncomplicated vaginal
delivery or primary (or planned) caesarean section in
women with heart disease is not recommended [17,46,77].
However, the high morbidity and mortality associated
with cardiac infection, the risk of unpredictable complications and the relatively safety of antibiotic prophylaxis in patients who are already receiving it should
lead to consideration of antibiotic prophylaxis in all
high-risk cardiac conditions. Antibiotic therapy should
be administered 30 min before caesarean section or at the
beginning of spontaneous delivery.
Percutaneous therapy
Over the last 20 years, interventional cardiology has
emerged as a new therapeutic tool and as an effective
alternative to surgical therapy in several cardiac diseases,
such as valve stenosis and coronary artery disease [21].
Cardiac catheterization in the pregnant patient carries
the risk of fetal radiation exposure. The effects of radiation on the fetus depend on the radiation dose and the
gestational age at which exposure occurs. As previously
reported, the maximum permissible dose of radiation
to the pregnant woman has been set at 5 mGy. During
cardiac catheterization the mean radiation exposure
to the unshielded abdomen is 1.5 mGy, and less than
20% of this reaches the fetus because of tissue attenuation. Shielding the gravid uterus from direct radiation,
shortening fluoroscopic time and delaying the procedure until at least the completion of the period of
major organogenesis (> 12 weeks after menses) will minimize radiation exposure. With these provisions, cardiac
catheterization and interventional procedures during
621
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Chapter 20
pregnancy are safe for the fetus but should be considered
only in patients not manageable with medical therapy
(see Fig. 20.2).
Cardiac surgery
Open heart surgery can be performed during pregnancy,
with the same risk to the mother as outside pregnancy
but with a high incidence of fetal death (20–33%). The
best period to perform surgery is early in the second
trimester because in the first trimester it may cause abortion and later in the third trimester premature labour.
The poor fetal outcome is due to non-pulsatile blood
flow and hypotension associated with cardiopulmonary
bypass that can adversely affect placental blood flow.
Cardiopulmonary bypass in pregnancy must be performed
at high flow and high pressure, in normothermia, with
the shortest possible cross-clamping time.
Personal perspective
Pregnancy is a part of a woman’s life and not a disease
and most of the time is surprisingly well tolerated in
patients with mild or moderate heart disease. The
important rise in cardiac output that occurs particularly
in the second and third trimesters of pregnancy is
well balanced by the decrease in peripheral vascular
resistance. Pregnancy continuation should be
encouraged in the majority of cases, although patients
with a severe degree of mitral or aortic valve stenosis
remain particularly at risk. Pregnancy must be followed
by an experienced team, particularly in the third
trimester and during and after delivery.
The panorama of heart disease in women of
child-bearing age has changed and will change further.
The profile of the cases at risk has become different:
pulmonary hypertension and cyanotic heart disease
have become rare because of early correction during
infancy; palliated or corrected forms of congenital heart
disease with residual defects, valvular heart disease in
immigrants and cardiomyopathies with or without
coronary artery disease in older women have become
more frequent.
Multiple other factors can increase the risk during
pregnancy in women with heart disease. Older age at
pregnancy, smoking habits and twin or triple pregnancy
References
1 Lupton M, Otehng-Ntim E, Ayida G et al. Cardiac disease
in pregnancy. Curr Opin Obstet Gynecol 2002; 14: 137–143.
2 Thilen U, Olsson SB. Pregnancy and heart disease: a review.
Eur J Obstet Gynecol Reprod Biol 1997; 75: 43 –50.
3 Presbitero P, Contrafatto I. Pregnancy and the heart. In:
Crawford MH, Dimarco JP (eds.). Cardiology, 1999. London:
McGraw-Hill, pp. 530 –543.
4 Robson SC, Hunter S, Boys RJ et al. Serial study of factors
influencing changes in cardiac output during human
pregnancy. Am J Physiol 1989; 256: H1060 –H1065.
secondary to frequent in vitro fertilization are much
more common and have to be taken into consideration
when assessing the risk. Heart failure secondary to
impaired left or right ventricular function has become
a common complication in this setting and its early
recognition and treatment is mandatory. Correction
of residual defects or aortic or mitral valve disease,
particularly stenotic valves even with moderate
degrees of stenosis, should be considered before
pregnancy. Percutaneous procedures or minimally
invasive surgical repair can today be performed in
these young women with low rates of complications,
making it easier to accomplish pregnancy without
problems.
Rest is the first step in all patients at risk. Heart failure
should be managed according to conventional
guidelines, except for the use of ACE inhibitors because
of their known fetal toxicity. Particular attention should
be paid to fluid retention in the immediate postpartum
period. Interventional procedures or heart surgery,
particularly during the second and third trimesters, can
be done with acceptable risks for mother and fetus.
From the surgical standpoint, short pump runs with
high flow rates are essential criteria, ensuring low levels
of fetal loss.
5 Letsky E. Haematological changes during pregnancy. In:
Oakley C (ed.). Heart Disease in Pregnancy, 1997. London:
BMJ Publishing Group, pp. 19 –51.
6 Van Oppen ACA, Van Der Tweel I, Alsbach GPJ et al. A
longitudinal study of maternal hemodynamics during
normal pregnancy. Obstet Gynecol 1996; 88: 40–46.
7 Doig JC, McComb JM, Reid DS. Incessant atrial
tachycardia accelerated by pregnancy. Br Heart J 1992;
67: 266 –268.
8 Granger JP. Maternal and fetal adaptations during
pregnancy: lessons in regulatory and integrative
physiology. Am J Physiol 2002; 283: R1289–R1292.
9 Robson SC, Dunlop W, Boys RJ et al. Cardiac output during
labour. Br Med J 1987; 295: 1169 –1172.
TETC20 12/2/05 9:42 Page 623
Pregnancy and Heart Disease
10 Elkayam U. Pregnancy and cardiovascular disease.
In: Braunwald E (ed.). Heart Disease. A Textbook of
Cardiovascular Medicine, 1997, 5th edn. Philadelphia: WB
Saunders, pp. 1843 –1864.
11 Cole PL, Sutton MJ. Cardiovascular physiology of
pregnancy. In: Douglas PS (ed.). Cardiovascular Health and
Disease in Women, 1993. Philadelphia: WB Saunders,
pp. 305–328.
12 Mishra M, Chambers JB, Jakson G. Murmurs in pregnancy:
an audit of echocardiography. Br Med J 1992; 304:
1413–1414.
13 Wenger N, Hurst J, Strozier V. Electrocardiographic changes
in pregnancy. Am J Cardiol 1964; 13: 774 –778.
14 Mesa A, Jessurun C, Hernandez A et al. Left ventricular
diastolic function in normal human pregnancy. Circulation
1999; 99: 511–517.
15 Campos O, Andrade JL, Bocanegra J et al. Physiologic
multivalvular regurgitation during pregnancy: a
longitudinal Doppler echocardiographic study. Int J
Cardiol 1993; 40: 265 –272.
16 Nihoyannopoulos P. Cardiovascular examination in
pregnancy and the approach to diagnosis of cardiac
disorder. In: Oakley C (ed.). Heart Disease in Pregnancy,
1997. London: BMJ Publishing Group.
17 Oakley C, Child A, Lung B et al. Expert consensus
document on management of cardiovascular diseases
during pregnancy: The Task force on Management of
Cardiovascular Diseases During Pregnancy of the European
Society of Cardiology. Eur Heart J 2003; 24: 761–781.
18 Oakley C. Acyanotic congenital heart disease. In: Oakley C
(ed.). Heart Disease in Pregnancy, 1997 London: BMJ
Publishing Group.
19 Deal K, Wooley CF. Coarctation of the aorta and
pregnancy. Ann Intern Med 1973; 78: 706 –710.
20 Beauchesne LM, Connolly HM, Ammash NM et al.
Coarctation of the aorta: outcome in pregnancy. J Am
Coll Cardiol 2001; 38: 1728–1733.
21 Presbitero P, Prever SB, Brusca A. Interventional cardiology
in pregnancy. Eur Heart J 1996; 17: 182 –188.
22 Genoni M, Jenni R, Hoerstrup SP et al. Pregnancy after atrial
repair for transposition of the great arteries. Heart 1999;
81: 276–277.
23 Presbitero P, Somerville J, Rabajoli F et al. Corrected
transposition of the great arteries without associated defects
in adult patients: clinical profile and follow up. Br Heart J
1995; 53: 357–358.
24 Connolly HM, Warnes CA. Ebstein’s anomaly: outcome of
pregnancy. J Am Coll Cardiol 1994; 23: 1194 –1198.
25 Guèdes A, Mercier LA, Leduc L et al. Impact of pregnancy
on the systemic right ventricle after Mustard operation for
transposition of the great arteries. J Am Coll Cardiol 2004;
44: 433 – 437.
26 Siu SC, Sermer M, Colman JM et al. Prospective multicenter
study of pregnancy outcomes in women with heart disease.
Circulation 2001; 104: 515 –521.
27 Siu SC, Sermer M, Harrison D et al. Risk and predictors for
pregnancy related complications in women with heart
disease. Circulation 1997; 96: 2789 –2794.
28 Weiss BM, Zemp L, Seifert B et al. Outcome of pulmonary
vascular disease in pregnancy: a systematic overview from
1978 through 1996. J Am Coll Cardiol 1998; 31: 1650–1657.
29 Yentis SM, Steer PJ, Plaat F et al. Eisenmenger’s syndrome
in pregnancy: maternal and fetal mortality in the 1990s.
Br J Obstet Gynaecol 1998; 105: 921–922.
30 Oakley C. Pulmonary hypertension. In: Oakley C (ed.).
Heart Disease in Pregnancy, 1997. London: BMJ Publishing
Group pp. 97–111.
31 Geohas C, McLaughlin V. Successful management of
pregnancy in a patient with Eisenmenger syndrome with
epoprostenol. Chest 2003; 124: 1170 –1173.
32 Bildirici I, Shumway JB. Intravenous and inhaled
epoprostenol for primary pulmonary hypertension during
pregnancy and delivery. Obstet Gynecol 2004; 103:
1102 –1105.
33 Lacassie HJ, Germain AM, Valdes G et al. Management of
Eisenmenger syndrome in pregnancy with sildenafil and
l-arginine. Obstet Gynecol 2004; 103: 1118–1120.
34 Rubin LJ, Badesch DB, Barst RJ et al. Bosentan therapy for
pulmonary arterial hypertension. N Engl J Med 2002; 346:
896–903.
35 Arias F, Pineda J. Aortic stenosis and pregnancy. J Reprod
Med 1978; 20: 229 –232.
36 Banning AP, Pearson JF, Hall RJ. Role of balloon dilatation
of the aortic valve in pregnant patients with severe aortic
stenosis. Br Heart J 1993; 70: 544 –545.
37 Ben Ami M, Battino S, Rosenfeld T et al. Aortic valve
replacement during pregnancy. A case report and review of
the literature. Acta Obstet Gynecol Scand 1990; 69: 651–653.
38 Silversides CK, Colman JM, Sermer M et al. Early and
intermediate-term outcomes of pregnancy with congenital
aortic stenosis. Am J Cardiol 2003; 91: 1386–1389.
39 Presbitero P, Somerville J, Stone S et al. Pregnancy in
cyanotic congenital heart disease. Outcome of mother and
fetus. Circulation 1994; 89: 2673 –2676.
40 Burn J, Brennan P, Little J et al. Recurrence risks in
offspring of adults with major heart defects: results from
first cohort of British collaborative study. Lancet 1998; 351:
311–316.
41 Deanfield J, Thaulow E, Warnes C et al. Management of
grown-up congenital heart disease. Eur Heart J 2003: 24:
1035 –1084.
42 Nora JJ, Berg K, Nora AH. Cardiovascular Diseases. Genetics,
Epidemiology and Prevention, 1991. New York: Oxford
University Press.
43 Holder SE. Genetic counselling. In: Oakley C (ed.). Heart
Disease in Pregnancy, 1997. London: BMJ Publishing Group,
pp. 401–411.
44 Digilio MC, Casey B, Toscano A et al. Complete
transposition of the great arteries: patterns of congenital
heart disease in familial precurrence. Circulation 2001; 104:
2809 –2814.
45 Siu SC, Colman JM, Sorensen S et al. Adverse neonatal and
cardiac outcome are more common in pregnant women
with cardiac disease. Circulation 2002; 105: 2178–2184.
46 Bonow RO, Carabello B, de Leon AC. ACC/AHA guidelines
for management of patients with valvular heart disease: a
623
TETC20 12/2/05 9:42 Page 624
624
Chapter 20
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines. J Am
Coll Cardiol 1998; 32: 1486 –1588.
Reimold SC, Rutherford MB. Valvular heart disease in
pregnancy. N Engl J Med 2003; 349: 52 – 59.
Silversides CK, Colman JM, Sermer M et al. Cardiac risk in
pregnant women with rheumatic mitral stenosis. Am J
Cardiol 2003; 91: 1382 –1385.
de Souza JAM, Martinez EE, Ambrose JA et al. Percutaneous
balloon mitral valvuloplasty in comparison with open
mitral valve commissurotomy for mitral stenosis during
pregnancy. J Am Coll Cardiol 2001; 37: 900 –903.
Maron BJ, McKenna WJ, Vogel RA et al. ACC/AHA/ESC
clinical expert consensus document on hypertrophic
cardiomyopathy. J Am Coll Cardiol 2003; 42: 1–27.
Autore C, Conte MR, Piccininno M et al. Risk associated
with pregnancy in hypertrophic cardiomyopathy. J Am
Coll Cardiol 2002; 40: 1864 –1869.
Hung L, Rahimtoola S. Prosthetic heart valves and
pregnancy. Circulation 2003; 107: 1240 –1246.
Hanania G, Thomas D, Michel PL et al. Pregnancy in
patients with valvular prostheses: retrospective cooperative
study in France (155 cases). Arch Mal Coeur Vaiss 1994;
87: 429– 437.
Hirsh J, Fuster V, Ansell J et al. American Heart Association/
American College of Cardiology Foundation Guide to
warfarin therapy. Circulation 2003; 107: 1692 –1711.
Rowan JA, McCowan LME, Raudkivi PJ et al. Enoxaparin
treatment in women with mechanical heart valves during
pregnancy. Am J Obstet Gynecol 2001; 185: 633 –637.
Anticoagulation in Prosthetic Valves and Pregnancy
Consensus Report Panel and Scientific Roundtable
Discussion. Anticoagulation and enoxaparin use in patients
with prosthetic heart valves and/or pregnancy. Clinical
Cardiology Consensus Reports Atlanta, 2002, pp. 1–20.
Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents
during pregnancy. Chest 2001; 119 (suppl.): 122 –131.
Child AH. Management of pregnancy in Marfan syndrome,
Ehlers–Danlos syndrome, and other heritable connective
tissue disorders. In: Oakley C (ed.). Heart Disease in
Pregnancy, 1997. London: BMJ Publishing Group,
pp. 153–162.
Roth A, Elkayam U. Acute myocardial infarction associated
with pregnancy. Ann Intern Med 1996; 125: 751–762.
Ascarelli MH, Grider AR, Hsu HW. Acute myocardial
infarction during pregnancy managed with immediate
percutaneous transluminal coronary angioplasty. Obstet
Gynecol 1996; 88: 655 – 657.
Ray P, Murphy GJ, Shutt LE. Recognition and management
of maternal cardiac disease in pregnancy. Br J Anaesth 2004;
93: 428 – 439.
Collins JS, Bossone E, Eagle KA et al. Asymptomatic
coronary artery disease in a pregnant patient. A case report
and review of literature. Herz 2002; 27: 548 –554.
Cowan SW, Coscia LC, Philips LZ et al. Pregnancy outcomes
in female heart and heart–lung transplant recipients.
Transplant Proc 2002; 34: 1855 –1856.
Baron O, Hubaut J, Galetta D et al. Pregnancy and
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
heart–lung transplantation. J Heart Lung Transplant 2002;
21: 914 –917.
Brigs GC, Freeman RK, Yaffe SJ. Drugs in Pregnancy and
Lactation: A Reference Guide to Fetal and Neonatal Risk, 1998.
Baltimore: Williams & Wilkins.
Bloomfield TH, Hawkins DF. The effect of drugs on the
human fetus. In Setchell M, Ginsberg J (eds). Scientific
Foundations of Obstetrics and Gynaecology, 1991. Oxford:
Butterworth Heinemann, pp. 320 –336.
Elkayam U. Pregnancy and cardiovascular disease.
In: Braunwald E (ed.). Heart Disease. A Textbook of
Cardiovascular Medicine, 1997, 5th edn. Philadelphia:
WB Saunders, pp. 1843 –1864.
Opasich C, Russo A, Colombo E et al. Your cardiac patient
wants to become a mother. Risk considerations and advice.
Ital Heart J 2000; 1: 667–673.
Buttar HS. An overview of the influence of ACE inhibitors
on fetal–placental circulation and perinatal development.
Mol Cell Biochem 1997; 176: 61–71.
Blomstrom-Lundquist C, Scheiman MM, Aliot EM et al.
ACC/AHA/ESC Guidelines for the management of patients
with supraventricular arrhythmias. Circulation 2003; 108:
1871–1909.
Tan HL, Lie KI. Treatment of tachyarrhythmias during
pregnancy and lactation. Eur Heart J 2001; 22: 458–464.
Magee LA, Downar E, Sevner M et al. Pregnancy outcome
after gestational exposure to amiodarone in Canada.
Am J Obstet Gynecol 1995; 172: 1307–1311.
Natale A, Davidson T, Geiger MJ et al. Implantable
cardioverter defibrillators and pregnancy. A safe
combination? Circulation 1997; 96: 2808–2812.
Gowda RM, Khan IA, Mehta NJ et al. Cardiac arrhythmias
in pregnancy: clinical and therapeutic considerations.
Int J Cardiol 2003; 88: 129 –133.
Strasburger JF, Cuneo BF, Michon MM et al. Amiodarone
therapy for drug-refractory fetal tachycardia. Circulation
2004; 109: 375 –379.
Oudijk MA, Ruskamp JM, Ververs T et al. Treatment of fetal
tachycardia with sotalol: transplacental pharmacokinetics
and pharmacodynamics. J Am Coll Cardiol 2003; 42:
765 –770.
Sugrue D, Troy P, McDonald D et al. Antibiotic prophylaxis
against infective endocarditis: recommendations by
the American Heart Association. JAMA 1997; 277:
1794 –1801.
Montan S. Drugs used in hypertensive diseases in
pregnancy. Curr Opin Obstet Gynecol 2004; 16: 111–115.
Magee LA, Cham C, Waterman EJ et al. Hydralazine for
treatment of severe hypertension in pregnancy: metaanalysis. Br Med J 2003; 327: 955 –965.
Chiaffarino F, Parazzini F, Paladini D et al. A small
randomised trial of low-dose aspirin in women at high risk
of pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 2004; 112:
142 –144.
Coomarasamy A, Honest H, Papaioannou S et al. Aspirin for
prevention of preeclampsia in women with historical risk
factors: a systematic review. Obstet Gynecol 2003; 101:
1319 –1332.