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Documente Profesional
Documente Cultură
Review Article
Heart Disease and Pregnancy
AIKATERINI CHAMAIDI, MICHAEL A. GATZOULIS
Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital and the
National Heart & Lung Institute, Imperial College, London, UK
R
Key words: ecent advances in paediatric car- pregnancy are an increase in blood vol-
Pregnancy, pre- diology and cardiac surgery have ume, heart rate and cardiac output and a
pregnancy
counselling, enabled more than 85% of patients decrease in peripheral vascular resistance
pregnancy-related with congenital heart disease to survive (Figure 1).4
risk. to adulthood. Half of these patients are ñ The increase in blood volume (30-50%)
women, the majority of them of childbear- represents an adaptation process induced
ing age. Most interventions, however are by the increased metabolic demand of
not curative, about half of the women with the foetus. This increase starts as early as
congenital heart disease face the prospect the sixth week of pregnancy; the levels
of further surgery, arrhythmia, heart fail- peak by the 20th to 24th weeks of preg-
ure, and–if managed inappropriately–pre- nancy, and then are sustained until term
Manuscript received: mature death. The additional burden of or decrease. The underlying mechanism
July 30, 2006;
Accepted: pregnancy represents a new challenge for is presumably hormonal, but the exact se-
August 8, 2006. this growing number of patients with heart quence of events remains unclear.
disease.1 ñ Cardiac output increases in parallel with
The number of women of childbearing the increase in blood volume (30-50%).
Address: age with coronary artery disease is also ex- The rise of cardiac output in pregnancy is
Michael A. Gatzoulis pected to grow, because of both the ad- disproportionately greater than the in-
vanced maternal age and fertility, and the crease in heart rate and is therefore at-
Adult Congenital Heart tributable to an augmentation of stroke
adoption of the western style of life, which
Centre and Centre for
Pulmonary leads to a higher incidence of risk factors volume. As pregnancy advances, heart
Hypertension for coronary atherosclerosis.2 rate increases, approximately by 10 to 20
Royal Bromptom In the past few decades, rheumatic beats per minute, and becomes the more
Hospital and the
National Heart & Lung fever has decreased drastically in devel- predominant factor in increasing cardiac
Institute, Imperial oped countries. Nevertheless, rheumatic output.5
College fever remains problematic in the develop- – There is a remarkable fluctuation in
Sydney Street
ing countries. Immigrants represent an ad- resting cardiac output with changes in
London SW3 6NP, UK
e-mail: ditional population that may be at high risk, position; the compression of the inferi-
M.Gatzoulis@rbht.nhs.uk because of social reasons or because of or vena cava by the enlarged gravid
lack of screening for congenital heart dis- uterus in the supine position results in
ease in their countries of origin.3 decreased venous return and a conco-
mitant significant decrease in cardiac
output.6
Physiological changes during pregnancy,
– Due to this hyperdynamic status, mur-
delivery and the post-partum
murs develop in nearly all women dur-
The main physiological changes during ing pregnancy; they are usually soft mid-
systolic and their intensity may increase as cardiac in both heart rate and blood volume as uterine blood
output increases. A continuous murmur due to in- enters the circulating pool (300 to 400 ml of blood).
creased mammary blood flow may also be heard. The magnitude of the increase in cardiac output
Diastolic murmurs can be physiologic during preg- during contractions increases as labour progres-
nancy. However, echocardiography is also warrant- ses.
ed when a diastolic murmur is present. ñ Both systolic and diastolic blood pressures increase
– Among healthy pregnant woman, serial echocar- markedly during contractions because of compres-
diography usually demonstrates minor increases sion of the abdominal aorta by the uterus, resulting
in both ventricular diastolic dimensions, which re- in an increase in peripheral vascular resistance. The
main within the normal range, with a slight de- augmentation is greater during the second stage of
crease in left ventricular end-systolic diameter and delivery.
a minimal increase in the size of the left atrium. ñ In spite of the external haemorrhage associated with
Left ventricular contractility appears to be depress- delivery, cardiac output is significantly higher one to
ed in pregnancy, but the ejection fraction is main- two hours post-partum prior to initiation of placenta
tained because of the altered loading conditions.7 contractions. This 60% to 80% increase in cardiac
Increased circulating volumes result in increased output occurs immediately after delivery, because of
transvalvular flow velocities. Minor degrees of atri- the temporary increase in venous return due to relief
oventricular valve regurgitation are common and of of caval compression and the additional blood shift-
no clinical significance.8 ing from the contracting uterus into the systemic cir-
ñ Aortic root diameter increases during pregnancy, culation.
by about 2-3 mm.9 The cardiovascular adaptations associated with
ñ The 30% fall in systemic vascular resistance is a fun- pregnancy regress by approximately six weeks after
damental physiological change during pregnancy. delivery. 10
– This afterload reduction is due to the high flow,
low resistance, maternal placental circulation.
Preconception counselling
– Pulmonary pressures remain normal during preg-
nancy, suggesting a similar decrease in pulmonary Discussions about future pregnancies, family plan-
vascular resistance to accommodate the increased ning and contraception should begin in adolescence,
cardiac output. both to prevent accidental and possibly dangerous
Haemodynamics are altered substantially during pregnancies and to allow patients to plan their lives.11
labour and delivery, secondary to anxiety, pain, and Counselling should address how pregnancy may af-
uterine contractions. fect not just the mother, but also the foetus. It should
ñ Uterine contractions result in a 50% acute increase ideally be provided in a joint clinic by an obstetrician
Table 1. Generic cardiac risk factors for adverse maternal out- Overall, there is a higher incidence of foetal and
comes during pregnancy. neonatal adverse events, including intrauterine growth
ñ Poor functional class before pregnancy (NHYA class >II). restriction, premature birth, intracranial haemorrhage,
ñ Impaired left ventricular function (ejection fraction <40%). and foetal loss, in women with heart disease com-
ñ Left heart obstruction, mitral valve area <2 cm2 , aortic valve area pared with the general population. By far the most
<1.5 cm2 , left ventricular outflow tract peak blood pressure gradi- common complication in the foetus is growth restric-
ent measured by Doppler echocardiography >30 mmHg.
ñ Preconception history of adverse cardiac events such as sympto-
tion, particularly when the increase in cardiac output
matic arrhythmia, stroke, transient ischaemic attack and pul- is inadequate so that the flow to the placenta is re-
monary oedema. stricted. This is amplified by any other obstetric risk
factors.
The estimated risk of a cardiac event in pregnancies without risk factor was
5%, with one risk factor 27%, and 75% if two risk factors were present. In a prospective study that examined the inci-
dence of adverse neonatal outcomes in women with
heart disease compared to healthy women, the inci-
event in pregnancies without risk factor was 5%, with dence was 18% and 7% respectively (Table 2). In pa-
one risk factor 27%, and with two risk factors 75%. tients with heart disease without obstetric complica-
Regarding patients with congenital heart disease in tions and without known risk factors for neonatal
particular, a recent publication described 90 pregnan- complications the actual incidence of neonatal com-
cies in 53 women, with 19.4% of primary maternal car- plications was similar to that in healthy women.18
diac events; pulmonary oedema occurred in 16.7% and
sustained arrhythmias in 2.8%. There were no maternal
deaths. In addition to the previous risk factors reported Management of pregnancy, delivery and the post-partum
in the CARPREG study, right ventricular dysfunction
The level of antenatal care and monitoring required
in patients with ventriculo-arterial concordance and/or
should be determined before pregnancy, or when this
severe pulmonary regurgitation were independent risk
is not possible as soon as pregnancy is confirmed. See
factors for cardiac events, but not for death.15
Table 3, which includes risk stratification of heart dis-
eases during pregnancy. As most general obstetricians
The risk for the foetus will see only few patients with moderate to severe
heart disease, referral to a specialist centre for coun-
The potential for congenital heart disease in the off-
selling is strongly advisable.
spring must be considered before conception. Over-
Low risk patients can continue with their antenatal
all, the chance is 4%16 compared with a background
care locally, taking into account the specialist recom-
of 0.8% for the general population.17
mendations.19 Moderate to high-risk patients should be
For lesions with autosomal dominant inheritance—
cared for in a tertiary, multidisciplinary environment.
DiGeorge, Marfan syndrome, Noonan syndrome and
Women with significant valvular heart disease should be
hypertrophic cardiomyopathy—the risk of recurrence
evaluated periodically, including echocardiography
of heart disease can be as high as 50%. If the muta-
(every trimester and whenever there is a change in sym-
tion is known, prenatal diagnosis at 12 weeks of gesta-
ptoms).
tion can be made by corionic biopsy.
Careful planning for antenatal care and delivery are
A foetal nuchal translucency measurement at 12-
clearly required. Some patients may benefit from hospi-
13 weeks gestation is a useful first screening test (the
incidence of congenital heart disease is only 1/1000
Table 2. Generic risk factors for adverse neonatal outcome.
with normal nuchal thickness). A specialist foetal car-
diac echo scan at 14-16 weeks gestation should be of- ñ Poor functional class before pregnancy (NHYA class >II).
fered to detect moderate to severe congenital heart ñ Impaired left ventricular function (ejection fraction <40%).
lesions, and this may need repeating at 20 weeks. ñ Left heart obstruction, mitral valve area <2 cm2, aortic valve
area <1.5 cm2, left ventricular outflow tract peak blood pressure
For women with cyanotic or stenotic lesions, rou-
gradient measured by Doppler echocardiography >30 mmHg.
tine ultrasound biometry of the foetus is warranted. ñ Cyanosis.
Close assessment of foetal growth is also advisable in ñ Anticoagulant therapy.
patients with systemic hypertension or taking beta- ñ Multiple gestation.
blockers. Maternal drugs may need changing before ñ Smoking.
ñ Maternal age less than 20 or more than 35.
conception or once pregnancy is confirmed.
Pulmonary hypertension (mortality 30-50%) Cyanotic lesions without pulmonary hyper- Left to right shunts
ñ Eisenmenger syndrome tension Functionally normal bicuspid aortic valve
ñ Primary pulmonary hypertension Single ventricle physiology (with or without Biological prosthesis without residual car-
Fontan) with good systemic ventricular func- diac dysfunction
Univentricular physiology with or without tion
Fontan with severe dysfunction Asymptomatic moderate to severe mitral
Mechanical prosthesis or aortic regurgitation without left ventri-
Severe aortic/mitral stenosis
Not severe aortic/mitral valve stenosis cular dysfunction
Marfan syndrome with severe aortic root
dilatation Severe pulmonary stenosis Moderate pulmonary stenosis
Acute myocardial infarction during preg- Marfan syndrome without marked aortic Repair of Tetralogy of Fallot without resid-
nancy root dilatation ual lesions such as severe pulmonary regur-
Unrepaired coarctation of the aorta gitation
Severe systemic ventricular dysfunction:
Other repaired lesions without residual car-
ñ Dilated cardiomyopathy diac dysfunction
ñ Previous peripartum cardiomyopathy
ñ Right ventricular systemic ventricle with
severe dysfunction (corrected congeni-
tal transposition of the great arteries,
Mustard)
talisation during the third trimester for bed rest, close Antiarrhythmic drugs in pregnancy should be ad-
monitoring and oxygen therapy of cyanotic patients. ministered at the lowest effective dose and for the short-
est duration possible. Monotherapy is also preferable.23
Supraventricular tachycardias can be terminated by
Drugs used during pregnancy
vagal stimulation, or failing that, with intravenous ade-
Most commonly used cardiovascular drugs for pa- nosine.24 Beta blockers with beta-1 selectivity are the
tients with heart disease cross the placenta and expose first choice for prophylaxis of supra- or ventricular ta-
the foetus to their pharmacological effects.20 Drug ef- chycardia during pregnancy. Potentially life-threatening
fects are influenced by intrinsic pharmacokinetic pro- ventricular tachyarrhythmias are much less common
perties and by the complex physiological changes oc- and should be terminated by electrical cardioversion.
curring during pregnancy, requiring adjusting doses Electrical cardioversion is not contraindicated dur-
through pregnancy. ing pregnancy and should be used for any sustained
Some drugs also enter breast milk and may affect tachycardia causing haemodynamic instability and thus
the neonate and infant that way. The benefits and risks threatening foetal and maternal well-being. Foetal
for mother and foetus have to be weighed carefully. heart rate must be monitored and maternal airways
See Table 4, which shows the most common drugs used should be protected.
in cardiology.21,22 Amiodarone may be used with caution as a sec-
ond line drug in cases resistant to other antiarrhyth-
mic agents. It leads to neonatal hypothyroidism.
Complications during pregnancy
The presence of an implantable cardioverter-defib-
rillator does not itself contraindicate future pregnan-
Arrhythmias
cies. In a series of 44 pregnancies of women with such a
Both ectopics and sustained arrhythmias become more device the incidence of appropriate discharges was no
frequent during pregnancy. In general they are treated greater during than outside pregnancy, with good out-
in the same way as outside pregnancy but as conserva- comes for the mother and the foetus.25
tively as possible, although prevention of arrhythmia A pacemaker for the alleviation of symptomatic
and avoidance of the need for anticoagulation are clear- bradycardia can be implanted if needed. Echo guid-
ly desirable. ance can minimise the effects of radiation.
ñ Emergency caesarean section should be started, if with previous endocarditis or valvular prosthesis,
appropriate, as soon as cardiac arrest is confirmed. complex cyanotic congenital heart disease, surgically
The following should be considered: magnesium created systemic to pulmonary artery shunt or con-
sulphate excess, eclampsia with multi-organ failure, duit, bicuspid aortic valve), or those undergoing cae-
acute myocardial infarction, aortic dissection, massive sarean or operative vaginal delivery (forceps or ven-
pulmonary embolism, amniotic fluid embolism, and touse extraction).
trauma or drug overdose.
Heart failure
Thromboembolic disease
Normal pregnancy is accompanied by symptoms of
There is a five-fold increased risk of thromboembolic fatigue, a decrease in exercise capacity, and dyspnoea.
events during pregnancy in any woman and an eleven- Many patients with heart disease who are asympto-
fold increase during the puerperium, which is even matic may develop classic symptoms of heart failure
greater following caesarean section. Since cyanotic while pregnant.
heart disease is also an independent risk factor for Deterioration in New York Heart Association
thrombosis, pregnancy creates additional risk for these (NYHA) functional class alone is not an indication for
patients and prophylaxis with low molecular weight he- hospitalisation because of its subjectivity, taking into
parin is indicated in the second and third trimesters. consideration the effect of general pregnancy discom-
Treatment of deep venous thrombosis with low molecu- fort. Augmentation of jugular venous pulsation related
lar weight heparin is safe, but dose adjustment is re- to increased blood volume and leg oedema (often ob-
quired. served in late pregnancy) could lead to an erroneous di-
Patients with mechanical prostheses, who require agnosis of heart failure, or overestimation of its severity.
anticoagulation, place themselves and the foetus at par- If heart failure is well documented, bed rest, low
ticular risk during pregnancy. Management decisions salt diet and the classic treatment of heart failure is
must weigh the risk and benefits of warfarin versus he- recommended, including beta-blockers, digitalis and
parin (see below: “Anticoagulation in pregnancy”). oral diuretics. Angiotensin converting enzyme in-
Ideally, these issues should be considered much earlier hibitors and angiotensin receptor antagonists are con-
and alternatives to a metallic prostheses should be traindicated during pregnancy (see “Drugs in preg-
sought. nancy”). Hydralazine and nitrates can be used for this
Thrombosis of newer generation prosthetic valves, purpose.
including valves in the aortic position, has been re- In more severe cases, congestive heart failure will
ported. Thrombolysis is recommended27 but unfrac- require hospitalisation with intravenous diuretic ad-
tionated heparin may be used initially for small non- ministration, plus vasodilators for further afterload
obstructive thrombus. reduction. In life threatening cases (see “Peripartum
cardiomyopathy”) the temporary use of an intra-aor-
tic balloon pump or left ventricular assist device may
Endocarditis
help to stabilise the patient’s condition.4
Infective endocarditis is uncommon in pregnancy, but
when it occurs it presents difficulties in management.
Systemic hypertension
Antibiotics must be chosen to safeguard the life of the
mother but also to try to avoid damage to the foetus. Hypertensive disorders in pregnancy can be classified
The need for surgical treatment must be weighed as:
against the risk of foetal loss. It should not be delayed if • Chronic hypertension. Pre-existing hypertension,
endocarditis is life-threatening for the mother. before the 20th week of pregnancy. Superimposed
The American Heart Association and the Euro- pre-eclampsia develops in 20-25% of women with
pean Society of Cardiology28,29 do not currently recom- chronic hypertension and carries risks to both
mend the routine use of prophylactic antibiotics during mother and foetus.
labour for women with heart disease, but many high- • Gestational hypertension. Hypertension after the
risk centres practice it. Although proven benefits do not 20th week of pregnancy which is induced by preg-
exist, the use of intravenous antibiotic prophylaxis nancy.
seems reasonable in high-risk patients (such as those • Pre-eclampsia. Hypertension after the 20th week
of pregnancy which is induced by pregnancy and is further delay would prove detrimental to maternal
accompanied by proteinuria. health. Maternal mortality is similar to that for non-
Pre-eclampsia is the most common medical com- pregnant women. Foetal outcome is significantly influ-
plication of pregnancy and is associated with substan- enced, with foetal loss 30%. The complexity of an oper-
tial morbidity and mortality for both mother and ba- ation and the duration of cardiopulmonary bypass
by. It can cause abruption of the placenta, pulmona- (CPB) directly affect foetal mortality. Whenever possi-
ry oedema, disseminated intravascular coagulation, ble, delivery should be performed through caesarean
hepatic failure and prematurity. Women should be section after heparinisation and cannulation of the
screened regularly throughout pregnancy for pre- mother.
eclampsia (blood pressure and proteinuria) and those at If cardiac surgery is required, monitoring of the
high risk should be referred early for specialist care.30 foetus and uterine activity should be performed during
The primary goal of antihypertensive treatment is CPB. Uterine contractions during CPB are considered
to prevent maternal cerebral complications. For ethi- to be the most important predictor of foetal death, and
cal reasons there are no placebo controlled trials of are more prone to occur during rewarming. Prepara-
pharmacological regimens.31 The recommended goal tion and management should be oriented towards the
of therapy is the reduction of mean blood pressure to avoidance of any sudden changes of maternal flow.
below 126 mmHg, but not less than 105 mmHg, and Whenever possible, normothermic CPB should
the diastolic pressure to between 90 and 105 mmHg. be first choice for a pregnant patient.32
Delivery is the only definitive treatment for pre-
eclampsia and may be indicated depending on mater-
nal symptoms. There is no evidence that any other Delivery and post-partum
therapy, including antihypertensive drugs, alters the Labour and delivery must be planned carefully and well
underlying pathophysiology or improves outcome. in advance. Management of intrapartum care should be
Methyldopa remains the first line agent for pre- supervised by a team experienced in the care of women
eclampsia therapy, because of its safety and the ab- with cardiac disease (obstetrician, anaesthetist, mid-
sence of evidence of adverse effects in mothers or ba- wife) with a cardiologist readily available.
bies including long term paediatric follow-up. The Maternal monitoring during labour should be in-
dosage starts with 250 mg three times per day and in- dividualised, and usually includes continuous electro-
creases progressively to a maximum of 3 to 4 g per day. cardiographic monitoring and pulse oximetry, and oc-
Other drugs commonly used are labetalol, nifedipine, casionally invasive blood pressure recording.
clonidine and hydralazine. The principle is to manage the stress of labour in
Patients with severe pre-eclampsia who are at 23 to such a way that it does not exceed the woman’s capac-
34 weeks of gestation should be treated with bed rest, ity to cope with it.
intravenous magnesium sulphate for seizure prophylax- Vaginal delivery carries about half the risk of com-
is, blood pressure control, foetal assessment, and corti- plications of an elective caesarean section, for both the
costeroids for foetal lung maturity. mother and the foetus. However, prolonged and diffi-
cult labour should be avoided, and detailed continuous
monitoring of the foetus and the mother are mandatory.
Hypertensive crisis management
The threshold for assisted delivery, by either vacu-
Hydralazine may be given by slow intravenous injection um or forceps, should be low, in order to limit or avoid
of 5 mg, which can be repeated after 20 min; labetalol active maternal “bearing down” and a prolonged sec-
or nifedipine can also be used; in rare cases there may ond stage of labour. Labour should not be induced un-
be a need for nitroglycerine or nitroprusside. less for obstetric reasons or because of cardiovascular
Magnesium sulphate has been demonstrated to be deterioration. Spontaneous labour is usually quicker
more effective than nimodipine for prophylaxis against than induced and carries a higher chance of successful
seizures in women with severe pre-eclampsia. delivery.
Early epidural analgesia with a cardiostable drug
at low dose is important. For patients on anticoagula-
Cardiac surgery during pregnancy
tion, even at prophylactic doses, care needs to be tak-
Cardiac surgery during pregnancy should be reserved en during regional anaesthesia, to minimise the risk
for patients refractory to medical management in whom of neuroaxial haematoma.
Oxytocic drugs such as oxytocin and ergometrine, pregnancy in patients with atrioventricular septal de-
which improve uterine contraction, also have major fects. Although physiologically they behave similarly to
haemodynamic effects. Continuous infusion of oxy- other left to right shunts, a recent study examining the
tocin, at the lowest effective rate, in low volume fluid, outcome of 62 pregnancies in 29 women with atrioven-
has minimal cardiovascular effects and avoids the cir- tricular septal defects reported that pregnancy is not al-
culatory overload. ways well tolerated, predominantly because of a deteri-
For most cardiac conditions a normal vaginal deliv- oration in NHYA class (23%) and worsening of pre-ex-
ery, with good analgesia and a low threshold for forceps isting atrioventricular valvular regurgitation (17%).
assistance, is the safest mode of delivery for the mother, Offspring mortality was high (6.3%), primarily due to
since it is associated with less rapid haemodynamic recurrence of complex congenital heart disease.34
changes, and a lower risk of haemorrhage and infec-
tion.33 However, in some conditions caesarean section
is indicated (Table 5). Stenotic lesions
Ongoing monitoring during the puerperium and
Congenital aortic valve disease
post-partum period is necessary in high risk patients.
Coronary unit monitoring should be used if necessary, Congenital bicuspid aortic valve is the most common
especially in cyanotic patients and those with pul- cause of aortic valve stenosis that complicates pregnan-
monary hypertension, where the risk of maternal death cy. Women with symptomatic aortic stenosis should de-
remains high for up to 10 days. Most deaths in Eisen- lay pregnancy until after surgical repair. Women with
menger patients have been reported to occur in the first moderate to severe aortic stenosis may develop heart
or second week after delivery.19 failure, even if symptoms are not present prior to preg-
nancy. Early studies of critical aortic stenosis shared
high mortality rates (17%).35 Lower mortality and mor-
Specific heart conditions bidity have been reported in recent studies, however,
Congenital heart disease presumably reflecting better maternal care.36
The non-pregnant Doppler gradient across the
Left to right shunts valve may double during pregnancy, merely as a result
The effect of the increased cardiac output on the al- of the physiological changes. An apparent increase of
ready volume-overloaded right and left ventricle in pa- the pressure gradient during pregnancy should not nec-
tients with an atrial septal defect is counterbalanced by essarily cause alarm. In contrast, absence of such an
the decrease in peripheral vascular resistance. In the increase can be falsely reassuring, since it may herald
absence of pulmonary hypertension, pregnancy, labour left ventricular dysfunction or failure.
and delivery are well tolerated and maternal and foetal Cardiac surgery is indicated when there is clinical
complications are probably similar to those occurring in deterioration; successful palliation during pregnancy
the normal population. Infrequently, among patients by balloon valvuloplasty has been reported.37
with an atrial septal defect, paradoxical embolisation Aortic stenosis is an adverse risk factor for foetal
may be encountered if systemic vasodilation and/or ele- outcomes (see “Risk to the foetus”).
vation of pulmonary resistance promote a transient
right to left shunt. Coarctation of the aorta
Patients with restrictive ventricular septal defect
and with small patent ductus arteriosus also tolerate Maternal mortality with unrepaired coarctation of the
pregnancy well. There are few data on the effects of aorta has been estimated at 3%. The main complica-
tions reported relate to severe hypertension, including
aortic dissection. Changes in the aortic wall during
Table 5. Indications for caesarean section other than obstetric rea- gravid status increase the pre-existing risk of dissection
sons. in coarctation of the aorta.
ñ Marfan syndrome with aortic root dilatation >45 mm.
There was a 30% incidence of hypertension dur-
ñ Therapeutic treatment with warfarin at the onset of partum. ing pregnancy amongst 50 women with coarctation of
ñ If there is abrupt haemodynamic deterioration. the aorta and one death in a patient with Turner syn-
ñ Some authors recommend caesarean section in women with se- drome (died of Type A dissection).38
vere pulmonary hypertension or severe aortic stenosis.36
Coarctation of the aorta after repair is considered a
low risk lesion. During pregnancy, following coarctation Recently, concerns have been raised regarding the
repair, the risk of dissection and rupture is likely to be potential effect of pregnancy on right ventricular dilata-
reduced but not eliminated, especially in those with tion and function. In a recent retrospective study (43
aneurysm at the site of repair. In a recent series of preg- pregnancies) that sought to determine outcomes in pa-
nancies after coarctation repair there were no serious tients with tetralogy of Fallot, most of them repaired,
cardiovascular complications, but the incidence of hy- 7% of the women had adverse cardiovascular events,
pertension was still 22%.39 including supraventricular tachycardia, heart failure,
pulmonary embolism, and progression of right ventricu-
lar dilatation. Patients who had cardiovascular compli-
Pulmonary stenosis
cations during pregnancy also had severe right ventricu-
Mild to moderate pulmonary stenosis is well tolerated lar dilation or right ventricular dysfunction. The same
during pregnancy and foetal outcome is favourable. study also reported a higher rate of spontaneous foetal
Pregnancy in women with severe pulmonary stenosis loss, compared with the expected average.42
may precipitate right heart failure or atrial arrhythmia. Children of mothers with tetralogy of Fallot are
Balloon valvuloplasty may be required and yield a good more likely to have congenital heart disease, with re-
result for patients with valvar stenosis when symptoms ported incidence approximately 3%. It is believed that
of pulmonary stenosis develop or progress.40 15% of patients with tetralogy of Fallot have DiGeorge
syndrome, which is inherited with autosomal dominant
pattern.43
Unrepaired cyanotic conditions (without Eisenmenger
physiology)
Pulmonary atresia
The maternal risks associated with cyanosis during
pregnancy vary depending on the aetiology of the cya- In an early retrospective study evaluating the outcome
nosis, with a much higher rate of success if there is no of pregnancy in patients with pulmonary atresia, com-
pulmonary hypertension. Mortality during pregnancy in paring those with and without previous radical surgical
women with cyanosis without pulmonary hypertension repair, there were significant complications even in the
is reported as 5%. repair group. Patients with residual systemic to pul-
A large case series examining the outcome of 96 monary collaterals and those with elevated right ventric-
pregnancies in 44 women without Eisenmenger phy- ular pressures appeared to be at particularly high risk.44
siology reported a high rate of maternal cardiac events.
One death occurred and cardiovascular complications
Systemic right ventricle
were reported in 32% of the patients. Miscarriage, pre-
maturity and low birth weight were all associated with Both in the atrial switch operation (Mustard or Senning
cyanosis. The incidence of foetal complications was procedure) for repair of transposition of the great ar-
high, with a low live birth rate (43% of the pregnancies) teries, and in congenitally corrected transposition of the
and 37% premature births. The lowest live birth rate great arteries, the anatomic right ventricle supports the
(12%) was observed in those mothers with an arterial systemic circulation.
oxygen saturation of <85% at the beginning of preg-
nancy. It has been suggested that bed rest and O2 ad-
Transposition of great arteries with atrial switch
ministration can improve foetal outcome.41
Cardiovascular complications are largely related with
Repaired cyanotic conditions the presence of a systemic right ventricle. In women
without systemic ventricular dysfunction and in NYHA
Tetralogy of Fallot
classes I and II, pregnancy is well tolerated.45 Howev-
Tetralogy of Fallot is the most common cyanotic con- er, there are legitimate concerns of irreversible sys-
dition, currently with a large number of patients who temic ventricular dysfunction and dilatation, even in
have reached reproductive age after successful repair these women.46
during infancy. Classically, repaired tetralogy of Fal-
lot has been considered as a low risk lesion in terms
Transposition of great arteries with arterial switch
of both maternal and foetal outcomes, with no mater-
nal deaths being reported. In patients with previous arterial switch for transposi-
tion of the great arteries little is known about their Right atrial thrombus formation may occur, with
ability to cope with pregnancy, but it is fair to say that a risk of paradoxical embolism if the Fontan is fenes-
no major difficulties are anticipated. trated or following Fontan failure. Fontan patients
with a large right atrium and venous congestion have
to be monitored very carefully. It may be that such
Congenitally corrected transposition of the great arteries
patients should be considered for conversion to total
In a study with 41 patients, there were 105 pregnan- cavopulmonary connection before they embark on
cies with 73% live births and no maternal mortality. pregnancy.
In most patients who developed complications the di- The successful Fontan patient with a small right
agnosis was established during pregnancy.47 atrium or total cavopulmonary connection, in func-
tional class I or II with good left ventricular function,
can probably complete pregnancy with a normal live
Ebstein’s anomaly
birth at a relatively low risk. The need for anticoagu-
For the majority of patients with Ebstein’s anomaly, lant treatment has to be considered and plans should
pregnancy is well tolerated. However, increased risk be made before pregnancy.
of atrial arrhythmia can be anticipated and higher
rates of foetal loss have been reported. Pregnancy is
Marfan syndrome
associated with more maternal complications among
patients with Ebstein’s anomaly when resting cyanosis Eighty percent of patients with Marfan syndrome have
is present prior to pregnancy. some cardiac involvement, including mitral valve pro-
lapse and aortic root dilatation and dissection. Preg-
nancy is a high risk endeavour for affected females, as it
Univentricular physiology with or without the Fontan
is associated with a higher risk of dissection, occurring
operation
most often in the last trimester or the early post-par-
Overall, the risk for patients with single ventricle tum period.50
physiology (double-inlet ventricle, atrioventricular Full assessment should be performed before preg-
atresia and atrial isomerism) palliated with arterial nancy. The risk is lower for pregnancy following elec-
shunt is related with the presence of generic risks for tive aortic root replacement. A number of patients have
pregnancy. If pulmonary arterial hypertension is pre- had successful full term pregnancies without complica-
sent the risk is prohibitive. Successful pregnancy un- tions following elective aortic root replacement.
der proper cardiologic and obstetric supervision has Women with minimal cardiac involvement (aor-
been reported. tic root less than 40 mm, and without previous dis-
section, and no significant aortic or mitral regurgita-
tion) should be informed of a 1% risk of aortic dis-
The Fontan operation
section during pregnancy.51 Patients with an aortic
This procedure eliminates cyanosis and partially revers- root diameter more than 40 mm should be told that
es volume overload of the functioning single ventricle. the risk of dissection during pregnancy may be as
Patients have a limited ability to increase cardiac out- high as 10%.
put during pregnancy, however. Pregnancy needs to be monitored by echocardio-
There is limited information about pregnancy and graphy at regular intervals throughout pregnancy and
the Fontan operation. In the only series reported, in 21 for six months post-partum. Beta-blocker therapy
women with 33 pregnancies, 15 resulted in live births, 5 should be continued. If the aortic root diameter is 4.5
in elective therapeutic abortions and 13 in spontaneous cm or greater caesarean delivery is advisable. If nor-
abortions during the first trimester. There was no ma- mal delivery is planned the second stage should be ex-
ternal mortality in these 21 patients, although they pedited. The woman may be allowed to labour on her
probably represent a highly selected population.48 left side or in a semi-erect position to minimise stress
If ventricular dysfunction or obstruction of the Fon- to the aorta.
tan circulation exists, the risk of pregnancy is much high- Aortic dissection type A requires emergency car-
er. Atrial arrhythmias tend to develop or worsen, with a diac surgery. Acute dissection type B should be man-
rate of 25% sustained supraventricular arrhythmias be- aged medically with the same indications for surgery
ing reported in a recent review of the literature.49 in non-pregnant women.
sia and/or bone stippling. Its use during pregnancy LMWH during pregnancy. A recent report cited a
may also be associated with intracranial bleeding and high incidence of valve thrombosis related to the use
central nervous system abnormalities. In the main of LMWH, with higher mortality rates. A careful re-
meta-analysis examining cases where warfarin was used view of the reported cases, however, indicates that
throughout pregnancy the embryopathy risk was 6.4%, most, if not all of them were associated with an inade-
and not 30% as previously reported.66 The risk has quate dose, lack of monitoring, or sub-therapeutic an-
been thought to be dose related. It has been reported ti-Xa levels.68
that warfarin risk embryopathy is low in women who Because of changes in both intravascular volume
needed less than 5 mg of warfarin to maintain an ade- and body gain during pregnancy, administration of
quate international normalised ratio.67 LMWH on the basis of weight alone is inadequate,
Warfarin should be replaced by unfractionated and measurement of anti-Xa activity is necessary to
heparin from week 36 of the pregnancy. The interna- ensure effective anticoagulation. The most recent rec-
tional normalised ratio should be maintained at pre- ommendations of the American College of Chest
pregnancy levels. Physicians call for the use of LMWH given twice daily
to maintain four-hour post-injection anti-Xa levels of
around 1 U/ml.69
Unfractionated heparin (UFH)
Recent data suggest that such peak levels were
If heparin is used during pregnancy the risk of embry- associated with sub-therapeutic trough levels of less
opathy is 0% but maternal death is 6.7% with adjust- than 0.5 U/ml in the great majority of cases, and men-
ed doses. In addition to the discomfort of its adminis- tion the importance of routine measurements and
tration, heparin risks include thrombocytopenia and maintenance of trough levels within a therapeutic range
osteoporosis. Subcutaneous heparin during the first (0.6 to 0.7 U/ml). Peak levels should also be monitored
trimester is associated with a high incidence of throm- to prevent excessive anticoagulation (i.e. >1.5 U/ml), in
boembolic complications, particularly prosthetic which case an 8-hourly rather than 12-hourly dosing
thrombosis, and maternal death. should be used. To ensure patient compliance and ade-
The level of anticoagulation with heparin treat- quate prophylaxis, anti-Xa activity or activated partial
ment should be closely monitored and an activated thromboplastin time should be measured at least every
partial thromboplastin time of 2.5 times normal 2 weeks.
should be achieved. Resistance to moderate doses of The European Consensus does not approve the
UFH in high-risk women with old-generation pros- use of LMWH during pregnancy.59
thetic valves has been reported. To summarise:
If subcutaneous UFH is used, it should be started ñ A completely safe treatment for pregnant women
in high doses (17,500 to 20,000 U) and adjusted to who have a mechanical prosthesis does not exist.
prolong a 6-hour post-injection activated partial throm- ñ The European Consensus and the American Col-
boplastin time to within the therapeutic range. lege of Cardiology guidelines recommend the use
of warfarin through pregnancy given the high re-
ported mortality with UFH and the impression that
Low molecular weight heparin (LMWH)
warfarin embryopathy has been overstated. Howev-
In a non-pregnant status LMWH is superior in some er, there is an underreported incidence of intracra-
ways to UFH. LMWH does not cross the placenta nial bleeding.
barrier and it offers potential advantages, including ñ If women do not accept the risks of warfarin, he-
fewer bleeding complications, a lower frequency of parin has been proposed during the first trimester,
heparin-induced thrombocytopenia (although he- with a change to warfarin until the 35th week of
parin-induced thrombocytopenia seems to be rare in pregnancy.
pregnancy), a lower incidence of osteoporosis, superi- ñ Any anticoagulation therapy must be replaced by
or subcutaneous absorption and bioavailability, a UFH from the 36th week of gestation.
longer half life, and a more predictable dose response. ñ The use of LMWH during pregnancy is not official-
A lower rate of spontaneous abortion in patients with ly approved; there is a lack of data. If it is used with-
prosthetic heart valves has been shown when LMWH out dose control the risk of thrombosis is very high
was used compared with UFH. and the use of concomitant aspirin should be con-
Some concerns have been raised about the use of sidered.
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