Cardiovascular disease and

pregnancy: what to know

An article from the e-journal of the ESC Council for Cardiology Practice
Vol. 12, N 10 - 06 Dec 2013

Dr. Vassilis I. Barberis

Managing cardiovascular disease in pregnancy is a growing challenge for the
individual physician to whom the number of such presenting patients is
nevertheless,
usually
small.
This
article
reviews
the
practical
recommendations from a general and disease-specific standpoint.
TABLE OF CONTENTS:
I - GENERAL APPROACH

Physiological alterations and risk

Diagnostic approach
Fetal assessment and delivery

II - SPECIFIC CONDITIONS

Congenital heart disease and pulmonary hypertension

Aortic diseases
Valvular heart disease
Coronary artery disease and acute coronary syndromes
Peripartum cardiomyopathy
Other cardiomyopathies
Arrhythmias
Hypertensive disorders
Venous thromboembolism
III - CONCLUSION
IV - REFERENCES

Cardiovascular morbidity and mortality associated with pregnancy is

low however cases of cardiovascular diseases (CVD) during pregnancy are
increasing due to the :

rise in prevalence of hypertension, diabetes and obesity

older maternal age.

Advances in treatment of congenital heart disease (CHD) leading to more

CHD patients reaching childbearing age also have added to the number of
cases.
In the western world, congenital heart disease is the most frequent CVD
present during pregnancy - they are shunt lesions mostly, whereas rheumatic
heart disease dominates in the non-western countries. Hypertensive
disorders are the most frequent cardiovascular event during pregnancy (68%).
To help prevent, prepare for and address the needs of these situations, here
are the practical recommendations to look over, from a general and a
disease-specific approach.
I - GENERAL APPROACH
PHYSIOLOGICAL ALTERATIONS AND RISK
Physiological alterations during pregnancy are:
1.) haemodynamic: increases in blood volume, cardiac output (30-50%), and
heart rate (20-32 weeks), while there is a decrease in blood pressure and
systemic vascular resistance (second trimester)
2.) hemostatic: a classic hypercoagulable state increases the risk of thromboembolic events, further enhanced by venous stasis.
3) metabolic: disturbed glucose homeostasis, hypercholesterolemia, altered
drug pharmacokinetics requiring dose adjustments and monitoring.

Pre-pregnancy risk assessment and counseling is indicated in women with:

1.) Known or suspected congenital or acquired cardiovascular and aortic
disease - a review of any medications is needed to stop or substitute these
which are contraindicated during pregnancy
2.) Significant heart disease - they should be managed jointly by an
obstetrician and a cardiologist with relevant experience, and those at high
risk should be managed by a multidisciplinary team in a specialized center,
with a clear plan of follow-up during pregnancy and hospital delivery.

Predictors in the CARPREG risk score are poor functional status (NYHA class
> cyanosis,systemic (left) ventricular systolic dysfunction, left heart
obstruction, and history of prior cardiac events.
Each predictor is assigned one point. Patients with 0 predictors were at low
risk (5%), patients with 1 predictor were at intermediate risk (25%) and those
with >1 predictor was at high risk (75%) of adverse cardiac events during
pregnancy risk estimation scores.
CARPREG and ZAHARA (4,5). Look here for a look at biomarkers and risk
stratification of pregnancy. Find here treatment of the hypertensive pregnant
or lactating patient, and here treatment of the high-risk pregnant patient.
The 2011 ESC Guidelines (6) recommend the use of the modified World
Health Organization (WHO) classification for the assessment of maternal risk
(Table 1) (7).
Table 1. Modified WHO classification of maternal conditions
Risk of pregnancy by medical condition, Risk class

I - No detectable increased risk of maternal mortality and no/mild

increase in morbidity.
II - Small increased risk of maternal mortality or moderate increase in
morbidity.
III - Significantly increased risk of maternal mortality or severe
morbidity. Expert counseling required.
If pregnancy is decided upon, intensive specialist cardiac and obstetric
monitoring needed throughout pregnancy, childbirth, and the
puerperium.
IV - Extremely high risk of maternal mortality or severe morbidity;
pregnancy contraindicated. If pregnancy occurs termination should be
discussed. If pregnancy continues, care as for class III.

WHO : World Health Organization> Modified from Thorne S, MacGregor A,

Nelson-Piercy C. Risks of contraception and pregnancy in heart disease.
Heart 2006;92:1520 1525.
Women in conditions of the WHO IV category should be advised against
pregnancy, and in case they become pregnant and termination is not
considered, should be closely followed-up in an experienced tertiary center.
These conditions are:

pulmonary arterial hypertension (maternal mortality 17-50%),

severe symptomatic LV dysfunction (LVEF<30%, NYHA III-IV)

previous peripartum cardiomyopathy with any residual impairment of

LV function
severe mitral stenosis
severe symptomatic aortic stenosis
Marfan syndrome with aortic dilatation > 45mm, aortic dilatation >
50mm associated with bicuspid aortic valve and native severe aortic
coarctation.

Equally important is the WHO III category in which pregnancy is not directly
contraindicated but confers a high risk of maternal complications and should
be the object of close follow-up in an experienced tertiary center.
This includes the following conditions:

presence of mechanical valve

systemic right ventricle
Fontan circulation
unrepaired cyanotic heart disease
other complex congenital heart disease
aortic dilatation 40-45mm in Marfan syndrome
aortic dilatation 45-50mm associated with bicuspid aortic valve.

Pregnant patients with:

unoperated atrio-septal defect (ASD) or ventricular septal defect (VSD)

repaired Tetralogy of Fallot and most arrhyhmias

comprise the WHO II category and will generally go fairly well if

otherwise in good condition and uncomplicated (moderate morbidity
risk but small mortality risk), whereas the intermediate WHO II-III
category includes patients who could end up to the higher or lower risk
category depending on their individual characteristics.
The corresponding conditions for these patients are:
mild left ventricular impairment
hypertrophic cardiomyopathy
native or tissue valvular heart disease but not considered class I or IV
Marfan syndrome without aortic dilatation
aortic dilatation < 45mm associated with bicuspid aortic valve

repaired aortic coarctation.

Neonatal complications occur in 20-28% of patients with heart disease, with
neonatal mortality between 1% and 4%. Maternal and neonatal events are

highly correlated.
Maternal predictors of neonatal adverse events in women with heart disease
are:
baseline NYHA class > II or cyanosis
maternal left heart obstruction
smoking during pregnancy
multiple gestation
use of oral anticoagulants during pregnancy
mechanical valve prosthesis.
DIAGNOSTIC APPROACH
The risk of inheritance of cardiac abnormalities to the descendants is
significantly higher in women with CVD (between 3% and 50% depending on
type of disease) compared to parents without CVD.
Genetic testing may be useful in some cases (in cardiomyoapathies and
channelopathies, when other family members are affected and when other
genetic malformations associated with CVD are present).
All women with congenital heart disease should
echocardiography in the 19th to 22nd week of pregnancy.

be

offered

fetal

Detailed personal and family history is mandatory. Thorough clinical

examination for new or changing murmurs and signs of heart failure is
needed. If such findings, echocardiography should be performed.
Blood pressure, proteinuria especially in pregnant women at risk for
preeclampsia, pulse oximetry in congenital heart disease need to be taken.
Echocardiography for the evaluation of chest pain, 24-hour Holter monitoring
in cases of known history of paroxysmal or persistent arrhythmia or
palpitations are required.
Echocardiography is the preferred diagnostic tool during pregnancy due to
absence of radiation exposure, ease of use, bedside availability and ability to
evaluate a multitude of CVD (congenital heart disease, cardiomyopathy,
aortic disease, etc).
Trans-esophageal electrocardiography on the other hand is fairly safe but
rarely
needed.
Submaximal stress testing (80% of max.) could be performed in
asymptomatic patients withsuspected CVD.
Cardiac MRI (without gadolinium) only for congenital heart disease or aortic
disease if echo inconclusive indicated.

Chest X-ray, CT, cardiac cath, electrophysiological study generally not

recommended, may be considered with shielding of the fetus under very
strict
and
vital
indications
if
no
alternative.
FETAL ASSESSMENT AND DELIVERY
In families with heart disease, screening for congenital heart disease can
start as early as in the 13th week. Screening stands a good chance of
accurately detecting major congenital abnormalities (85% sensitivity, 99%
specificity) and allow parents to consider all options including termination in
case of major malformations. Optimal screening time for normal pregnancies
is 18-22 weeks, and studies should be performed by experienced specialists.
In general, the preferred mode of delivery is vaginal. In high risk cases,
delivery should take place in a tertiary centre under specialist
multidisciplinary care. No routine endocarditis prophylaxis is necessary.
There is no clear consensus regarding absolute contraindications to vaginal
delivery.
Cardiovascular conditions that should prompt elective caesarean section
consideration are:

cases of oral anticoagulation in pre-term labour

Marfan syndrome with aortic diameter > 45mm (class IIaC), or 4045mm (IIbC)
acute or chronic aortic dissection
severe intractable heart failure,
Eisenmenger syndrome
aortic stenosis (in some centers).

II SPECIFIC CONDITIONS
CONGENITAL HEART DISEASE AND PULMONARY HYPERTENSION
The risk of pregnancy depends on the underlying heart disease.
All patients with these conditions should receive pre-pregnancy assessment.
Patients with severe systemic ventricular dysfunction or advanced heart
failure
Pulmonary hypertension associated with high maternal mortality, even
in patients without significant previous disability or severe disease
Eisenmenger syndrome and saturation < 85% high maternal and fetal
mortality.
Severe symptomatic LVOT obstruction should be relieved before
pregnancy.
Cyanotic heart disease of moderate risk if previously repaired.

AORTIC DISEASES
During the peripartum period (last trimester and first weeks after delivery),
there is an increased susceptibility of the aorta to dissection. A larger aorta
confers higher risk, but there is no completely safe diameter.
In Marfan patients with aortic diameter >= 45mm prophylactic surgery is
indicated.
In patients with bicuspid valve, pre-pregnancy surgery should be considered
at diameters > 50mm.
When progressive dilatation occurs, aortic repair during pregnancy or directly
after delivery (depending on viability of the fetus) is indicated.
A Cesarean section is indicated when aortic diameter > 45mm.
VALVULAR HEART DISEASE
Moderate-severe mitral stenosis is poorly tolerated during pregnancy, and is
associated with heart failure in second and third trimester and
implies elevated
offspring
morbidity.
Intervention should preferably be percutaneous pre-pregnancy or after 20
weeks if intractable heart failure.
Patients with aortic stenosis should be evaluated before pregnancy to define
clinical
status.
An increase of cardiac output can produce marked increase of transaortic
gradient
during
pregnancy.
Pre-pregnancy aortic valve intervention is indicated for severe symptomatic
aortic
stenosis.
Left-sided regurgitant lesions are usually well tolerated during pregnancy due
to decreased systemic vascular resistance.
Pre-pregnancy surgery (preferably repair) when symptomatic or with
compromised
LV
function.
Regarding medical therapy for heart failure symptoms, always have in mind
that the significant category of RAS inhibitors (ACE-I, ARBs, renin inhibitors)
are absolutely contraindicated during pregnancy due to fetotoxicity.
Presence of mechanical prosthetic valve means a high risk pregnancy due to
need for anticoagulation and an increased risk of valve thrombosis during
pregnancy.
Oral anticoagulation (OAC) should be used until pregnancy is achieved. The
continuation of OAC throughout pregnancy is the safest strategy for the
mother (valid also for first trimester if the daily dose needed is low (warfarin
<
5mg).

Substitution with UFH or LMWH (with dose adjustment according to APTT or

anti-Xa activity correspondingly) between 6 and 12 weeks when higher
warfarin dose would be needed or anyway when the mother does not accept
the low risk of embryopathy associated with warfarin.
At the 36th week OAC is to be replaced by dose-adjusted UFH or LMWH. In
the event of obstructive valve thrombosis, critically ill patients will need
emergency
surgery
or
fibrinolysis.
Cesarean delivery is recommended when the patient is still on OAC to avoid
fetal cerebral bleeding.
CORONARY ARTERY DISEASE AND ACUTE CORONARY SYNDROMES
Although generally low, the rate of acute coronary syndromes during
pregnancy is expected to increase due to increasing maternal age and
prevalence
of
risk
factors.
Coronary artery dissection is more prevalent than in non-pregnant women, to have in mind when ACS occurs around delivery or postpartum.
Coronary angiography with the possibility of PCI preferred over thrombolysis
(it can diagnose coronary artery dissection too).
PERIPARTUM CARDIOMYOPATHY
Peripartum cardiomyopathy is idiopathic cardiomyopathy presenting with
heart failure and LV dysfunction towards the end of pregnancy or during the
first
months
following
delivery.
Exact aetiology is still uncertain, however several pathophysiological
mechanisms have been proposed.

These
factors
guidelines
for
heart failure apply.

can
the

develop very rapidly, and

management
of
acute

Patients not responding to medical therapy and inotropic support should be

transferred to centers capable of offering IABP, ventricular assist devices or

even heart transplantation. There is a high rate of spontaneous recovery

(approx.
50%).
Medical treatment should be according to heart failure guidelines except that
ACE inhibitors, ARBs and direct renin inhibitors are contraindicated during
pregnancy.
Urgent delivery in advanced heart failure or hemodynamic instability should
be processed by an experienced multidisciplinary team. There is 30-50% risk
of recurrence in subsequent pregnancies. Given the high morbidity,
pregnancy should be discouraged when EF not normalised, and counselling
delivered even if EF normal.
OTHER CARDIOMYOPATHIES
In dilated cardiomyopathy, consider pregnancy termination if EF < 20%. In
hypertrophic cardiomyopathy, frequently first time diagnosis in pregnancy.
Usually tolerated well, high risk if symptomatic high LVOT gradient. Bblockers preferred medical treatment.
ARRHYTHMIAS
Extrasystoles and sustained tachyarrhtyhmias are more frequent or manifest
for the first time during pregnancy.
Symptomatic exacerbation of SVT in 20-44% of cases.
Antiarrhythmic drugs potentially toxic for the fetus.
Adenosine I.V. treatment of choice for termination of SVT.
When new onset ventricular tachycardia at the last weeks of pregnancy or
first months after delivery, peripartum cardiomyopathy should be excluded.
Most frequent cause of VT in healthy pregnant women is idiopathic RVOT
tachycardia.
Catheter ablation may be necessary for drug-refractory, poorly tolerated
tachycardias (second trimester).
HYPERTENSIVE DISORDERS
Hypertension is the most common medical problem in pregnancy (up to 15%
of total). Hypertension is a major cause of maternal, fetal and neonatal
morbidity
and
mortality.
Blood pressure measurements are necessary at least on two occasions and
urinalysis is also needed to detect proteinuria.
1. Pre-existing hypertension (either precedes pregnancy or develops
before 20 weeks)

2. Gestational hypertension (develops after 20 weeks gestation)

3. Pre-eclampsia (5-7% of pregnancies): When new-onset hypertension is
combined with significant proteinuria (>300mg/24h) or headache,
visual disturbance, abdominal pain, low PLT or elevated liver enzymes.
Oedema no longer considered diagnostic. Frequent cause of
prematurity. Delivery is the ultimate cure for this condition. Association
with peripartum cardiomyopathy
4. Pre-existing hypertension plus superimposed gestational hypertension
with proteinuria.
5. Antenatally unclassifiable hypertension.
The drug of choice and safest for hypertension in pregnancy is -Methyldopa
(for mild-moderate cases).
In more severe hypertension and pre-eclampsia, will use labetalol,
metoprolol and/or nifedipine. ACE-I, ARBs, and renin inhibitors are
contraindicated
during
pregnancy
(fetotoxicity).
For severe hypertension (SBP>=170mmHg and/or DBP>=110mmHg,
hospitalization
is
indicated.
Breastfeeding does not increase BP in the nursing mother and can be
encouraged; however antihypertensive medication is excreted in the
milk. Hypertensive disorders in pregnancy are important risk factors for CVD
in later life.
VENOUS THROMBOEMBOLISM
There is an increased risk for venous thromboembolism (VTE) during
pregnancy and puerperium, significant cause for morbidity and
mortality. Caesarean
sections
increases
this
risk.
D-dimers and vein ultrasonography are used to exclude pulmonary embolism
in pregnant women with acute onset or worsening dyspnea.
Low-molecular weight heparin is the drug of choice for prophylaxis and
treatment of VTE in pregnant patients.
CONCLUSION
Knowledge of the principles of management of cardiovascular disease
associated with pregnancy is important in order to allow clinicians to offer
reliable pre-pregnancy counseling and optimize maternal and fetal outcome
when pregnancy occurs. This often represents a challenge, as long as certain
therapies may have diverse effects on the mother and fetus. We hope that
this review offered the cardiologist with tools for an up-to-date approach.
Nevertheless most of the recommendations included in relevant guidelines

have a level C evidence due to the lack of prospective or randomized trials.

Therefore, large databases of pregnancy complications (such as
the ROPAC and peripartum cardiomyopathy ESC registries), genetic testing
and risk assessment are needed in order to fill the gaps in evidence, enhance
our knowledge and improve our clinical practice in the management of these
patients.
REFERENCES
1. Outcome of pregnancy in patients with structural or ischaemic heart
disease: results of a registry of the European Society of Cardiology.
Roos-Hesselink JW et al; ROPAC Investigators.
Eur Heart J. 2013 Mar;34(9):657-65.
2. Changing mortality in congenital heart disease.
Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ.
J Am Coll Cardiol. 2010 Sep 28;56(14):1149-57.
3. Hypertensive disorders of pregnancy.
Peters RM, Flack JM.
J Obstet Gynecol Neonatal Nurs. 2004 Mar-Apr;33(2):209-20.
4. Prospective multicenter study of pregnancy outcomes in women with heart
disease.
Siu SC et al. Cardiac Disease in Pregnancy (CARPREG) Investigators.
Circulation. 2001 Jul 31;104(5):515-21.
5. Predictors of pregnancy complications in women with congenital heart
disease.
Drenthen W et al; ZAHARA Investigators.
Eur Heart J. 2010 Sep;31(17):2124-32.
6. ESC Guidelines on the management of cardiovascular diseases during
pregnancy: the Task Force on the Management of Cardiovascular Diseases
during Pregnancy of the European Society of Cardiology (ESC).
European Society of Gynecology (ESG); Association for European Paediatric
Cardiology (AEPC); German Society for Gender Medicine (DGesGM), RegitzZagrosek V et al; ESC Committee for Practice Guidelines.
Eur Heart J. 2011 Dec;32(24):3147-97.
7. Risks of contraception and pregnancy in heart disease.
Thorne S, MacGregor A, Nelson-Piercy C.
Heart. 2006 Oct;92(10):1520-5.
8. Outcome of pregnancy in women with congenital heart disease: a
literature review.
Drenthen W et al; ZAHARA Investigators.
J Am Coll Cardiol. 2007 Jun 19;49(24):2303-11.
9. Pregnancy outcomes in women with congenital heart disease.
Khairy P, Ouyang DW, Fernandes SM, Lee-Parritz A, Economy KE, Landzberg

MJ.
Circulation. 2006 Jan 31;113(4):517-24.
10. Recurrence risks in offspring of adults with major heart defects: results
from first cohort of British collaborative study.
Burn et al.
Lancet. 1998 Jan 31;351(9099):311-6.
11. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the
diagnosis and management of patients with Thoracic Aortic Disease.
Hiratzka LF, et al
Circulation. 2010 Apr 6;121(13):e266-369.
12. Guidelines on the management of valvular heart disease (version 2012)
Joint Task Force on the Management of Valvular Heart Disease of the
European Society of Cardiology (ESC); European Association for CardioThoracic Surgery (EACTS), Vahanian A et al.
Eur Heart J. 2012 Oct;33(19):2451-96.
13. Management of pulmonary arterial hypertension during pregnancy: a
retrospective, multicenter experience.
Duarte AG, Thomas S, Safdar Z, Torres F, Pacheco LD, Feldman J, DeBoisblanc
B.
Chest. 2013 May;143(5):1330-6.
14. Guidelines for the diagnosis and treatment of pulmonary hypertension:
the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of
the European Society of Cardiology (ESC) and the European Respiratory
Society (ERS), endorsed by the International Society of Heart and Lung
Transplantation (ISHLT).
Gali N, et al L, Zellweger M, Simonneau G; ESC Committee for Practice
Guidelines (CPG).
Eur Heart J. 2009 Oct;30(20):2493-537.
15. The immediate and long-term impact of pregnancy on aortic growth rate
and mortality in women with Marfan syndrome.
Donnelly RT, Pinto NM, Kocolas I, Yetman AT.
J Am Coll Cardiol. 2012 Jul 17;60(3):224-9.
16. Cardiac risk in pregnant women with rheumatic mitral stenosis.
Silversides CK, Colman JM, Sermer M, Siu SC.
Am J Cardiol. 2003 Jun 1;91(11):1382-5
17. Anticoagulation of pregnant women with mechanical heart valves: a
systematic review of the literature.
Chan WS, Anand S, Ginsberg JS.
Arch Intern Med. 2000 Jan 24;160(2):191-6.
18. Acute myocardial infarction associated with pregnancy.
Roth A, Elkayam U.
J Am Coll Cardiol. 2008 Jul 15;52(3):171-80.
19. Current state of knowledge on aetiology, diagnosis, management, and
therapy of peripartum cardiomyopathy: a position statement from the Heart

Failure Association of the European Society of Cardiology Working Group on

peripartum cardiomyopathy.
Sliwa K, et al; Heart Failure Association of the European Society of Cardiology
Working Group on Peripartum Cardiomyopathy.
Eur J Heart Fail. 2010 Aug;12(8):767-78.
20. Diagnosis and management of peripartum cardiomyopathy.
Blauwet LA, Cooper LT.
Heart. 2011 Dec;97(23):1970-81.
21. Recurrence rates of arrhythmias during pregnancy in women with
previous tachyarrhythmia and impact on fetal and neonatal outcomes.
Silversides CK, Harris L, Haberer K, Sermer M, Colman JM, Siu SC.
Am J Cardiol. 2006 Apr 15;97(8):1206-12.
22. Management of hypertension before, during, and after pregnancy.
James PR, Nelson-Piercy C.
Heart. 2004 Dec;90(12):1499-504.
23. The relationship between Preeclampsia and Peripartum Cardiomyopathy:
a Systematic Review and Meta-Analysis.
Bello N, Hurtado Rendon IS, Arany Z.
J Am Coll Cardiol. 2013 Aug 23. [Epub ahead of print].

Journal
in
NCM 102
(Cardiovascular
disorders and
Pregnancy)
Submitted by : Almario ,
Michelle
Submitted to:
Grace Antoni RN, MAN, Ph. D.