1. health and fitness
2. disease
3. heart disease

Keeping Mom Heart
Healthy:
Cardiovascular
Disease in Pregnancy
Rafic F. Berbarie
Berbarie,, MD
HeartPlace Cardiology
April 27, 2013
BHVH Annual CV Summit
Objectives and Outline


Summarize the general cardiovascular
physiological changes that occur during
pregnancy
Identify the hemodynamic consequences of
pregnancy on specific cardiac lesions and
disorders
–
–
–
–

V l l Heart
Valvular
H t Disease
Di
and
d Congenital
C
it l Heart
H t Disease
Di
Pulmonary and Systemic HTN
Cardiomyopathies
Ischemic Heart Disease
List the cardiovascular conditions associated
with a high risk pregnancy
Or…How do we get from here
to there?
General approach to treating
cardiac disease in pregnancy
Three steps, or questions to ask:
1. Can mom become pregnant or can the
pregnancy continue?
2. Are
A there
th
therapeutic
th
ti maneuvers to
t h
help
l
mom and baby?
3. What type of delivery will be
recommended?

Clinical Case Examples

23 yo with Marfan syndrome 33 weeks
pregnant with ascending aorta measuring
3.6 cm and mitral valve prolapse with no
significant regurgitation.
regurgitation Her BP is
110/70mmHg.
26 yo G2P1 with Marfan syndrome and
chronic systemic HTN with Type B aortic
dissection 23 weeks pregnant. Ascending
aorta measures 4
4.2
2 cm by
echocardiogram. BP is 140/90mmHg.
 Developed Type B dissection at 38 weeks
during first pregnancy and was “advised”
against becoming pregnant again.







37 year old G2P1 who is 6 weeks pregnant with
twins
Four weeks prior underwent PCI of the LAD with
drug eluting stent for unstable angina
Had PCI to a diagonal about 6 months prior also
with DES
First pregnancy complicated by placenta previa,
pre ecclampsia, and premature delivery
On clopidogrel and aspirin
Now what???
Scope of the problem
Pre-existing maternal heart disease and
PreHTN complicate 1% of pregnancies in the
US
 Add in growing number of adult congenital
heart disease patients1

– 800,000 adults
– More than 95% of infants expected to survive
into adulthood and reproductive years
1. Warnes, CA. JACC 2005;46:1-8.
Why is this important?
Pregnant women 'four times as
likely to have heart
attack‘
By Kate Devlin,
Medical Correspondent
Last updated: 07/07/2008
Why is this important?
Hypertension In Pregnancy
Has Later Risk
Study Shows Women More Likely To
Have Heart Disease
If They Had High Blood Pressure During
Pregnancy
Feb. 6, 2007
Sabour, S. Hypertension, 2007; vol 49: pp
1-2.
Cardiovascular changes
Appear in the 1st trimester and peak in the
late 2nd and early 3rd
 Increases in:

– Blood
Bl d volume,
l
CO
CO, HR,
HR SV

Decreases in:
– SVR, SBP, DBP

So, pregnancy is a high volume, low
resistant state
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
Physiological changes in pregnancy
More on CV
physiology
During labor and delivery, increase in
cardiac output and stroke volume from:

– Labor pain
– Uterine contractions
– Following placenta delivery
 Another auto
auto--transfusion and CO and SV increase
by 80%
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
World Health Organization Risk
stratification


Class II--IV (low to contracontra-indicated)
Most important to remember contracontraindications:
1 Pulmonary HTN
1.
2. Systolic ventricular dysfunction
– NYHA FC III or IV
3. Severe left sided obstructive lesions
– Aortic and mitral valve stenosis
4. Marfan with dilated aortic root (> 45mm)
Thorne, SA, et al. Heart 2006;92:1520-25.
CARPREG Trial
Canadian multicenter, prospective study of
pregnancy outcomes in women with heart
disease
 Enrolled 562 pregnant women

– 19941994-99

Study followed patients thru pregnancy,
delivery, and 6 months after
Siu, SC, et al. Circulation. 2001;104:515-521.
Principal cardiac lesions in
CARPREG
Congenital
g
Acquired
Arrhythmic
Siu, SC, et al. Circulation. 2001;104:515-521.
CARPREG Study
Combined fetal, maternal, and neonatal
mortality of 3%
 13% incidence of primary cardiac events

– Mostly tachyarrhythmia and pulmonary edema
Siu, SC, et al. Circulation. 2001;104:515-521.
Morbidity and mortality assessment
Event rate (%)
5
30
60

CARPREG scoring system, 1 point for:
–
–
–
–

Points
0
1
>1
cyanosis or NYHA FC > II
Left heart obstruction
LVEF < 40%
Prior cardiac event
Events in study defined as CHF, arrhythmia,
CVA, cardiac arrest, or death
Siu, SC, et al. Circulation. 2001;104:515-521.
ZAHARA study
Retrospective European study of 1802
women completing 1302 pregnancies
 Most common cardiac complications:

– Arrhythmias
A h th i (4.7%)
(4 7%)
– CHF (1.6%)
– Obstetrical complications : Mostly HTN related
– NeoNeo-natal complications: Premature birth,
small for gestational age and 4% mortality
Drenthen, W, et al. Euro heart journal. 2010. 31. 2124-32.
ZAHARA study
study--new scoring
system

Factors associated with maternal
complications:
– Mechanical valve
– Left heart obstruction
– History of arrhythmias
– Cardiac medication prior to pregnancy
– Cyanotic heart disease
– NYHA FC >=2 pre
pre--pregnancy
– AV valve regurgitation
Drenthen, W, et al. Euro heart journal. 2010. 31. 2124-32.
Nothing is perfect….

Neither scoring system accounts for:
– Pulmonary hypertension
– Dilated ascending aorta
Labor and Delivery

Vaginal delivery preferred method
– Forceps or vacuum delivery used to shorten
2nd stage of labor

Only cardiac indications for C
C--section
– Aortic dissection
– Marfan syndrome with dilated aortic root
– Failure to switch from warfarin to heparin 2
weeks before delivery
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
Antibiotic endocarditis prophylaxis?

The committee (ACC/AHA) concluded that only an
extremely small number of cases of infective endocarditis
may be prevented

Only for patients with underlying cardiac conditions
associated
i t d with
ith the
th highest
hi h t risk
i k off adverse
d
outcome
t
from
f
infective endocarditis

Dental procedures

Administration of antibiotics solely to prevent
endocarditis is not recommended for patients who
undergo a GU or GI tract procedure.
J Am Coll Cardiol, 2008; 52:676-685
Which cardiac drugs are OK to
give to my pregnant patient?
CV drugs and pregnancy
FDA Category
Interpretation
A
No risk.
B
N risk
No
i k iin humans.
h
C
Risk cannot be ruled out.
D
Positive evidence of risk
X
Contra-indicated in pregnancy
Safe CV drugs and pregnancy

Beta--Blockers
Beta

Heart rate controlling drugs

Anti--arrythmics
Anti

Calcium channel blockers
– Metoprolol,
Metoprolol, sotalol,
sotalol, labetalol
– Digoxin,
Digoxin, Adenosine
– Lidocaine,
Lidocaine, Class IA and IC (Quinidine
(Quinidine 1st choice?)
– Verapamil,
Verapamil, nifedipine
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
Safe CV drugs and pregnancy

Other drugs for hypertension
– 1st line agents are Hydralazine and alpha
alpha--Methlydopa
– Careful with diuretics

Anti--coagulation
Anti
l
and
d antianti-platelet
l l
– Heparin and enoxaparin
– Aspirin and clopidogrel probably safe
– Although ASA not to be used beyond 28 weeks
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
CV drugs and pregnancy

UNSAFE drugs:
– Warfarin
 Depends on dose, < 5 mg is acceptable
– Amiodarone
– ACEIs, ARBs, renin inhibitors
– Statins
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
Specific Cardiac Lesions and
Disorders
Normal pregnancy findings
History
Physical Exam
Fatigue
Midsystolic murmur at LUSB
Exercise intolerance
Continuous murmur
Palpitations
S3 gallop
Edema
JVD with a,v waves
Orthopnea
Edema
Stout KK, Otto CA. Heart. 2007 May;93(5):552-8.
Mitral stenosis

Most commonly encountered valvular
lesion in the pregnant woman

Pressure gradient increase across the
stenotic MV
– Rheumatic heart disease
– From increases in HR and SV
– Leads to increased left atrial pressure
– Worsening or development of symptoms
– Atrial arrhythmias
Elkayam, U, Bitar, F. JACC 2005;46:223-30
How does Mom do with mitral
stenosis?
100
90
80
70
60
Event rate 50
40
30
20
10
0
Mild
Moderate
Severe
HF
Arrhy.
Meds Admits
Hameed A, et al. JACC 2001;37:893-9.
Mitral stenosis

Maternal outcomes:
– Other studies1,2 with similar results
 Risk of maternal cardiac events increases with
severity of MS and a worse NYHA FC to begin with
 Most
M t common events
t are HF and
d atrial
t i l arrhythmias
h th i
– Mortality rare3
1. Silversides, C, et al. AJC 2003;91:1382-5.
2. Barbosa PF, et al. Arq Bras Cardiol 2000;75:215-24.
3. Elkayam, U, Bitar, F. JACC 2005;46:223-30
Treating mitral stenosis in pregnancy

If already pregnant
– Mild to moderate MS can usually be managed
medically

Balloon mitral valvuloplasty
– Should be done after 1st trimester

MV surgery
– Only for those refractory to medical therapy
and not candidates for balloon
 High rate of fetal loss with CPB (30%)
Elkayam, U, Bitar, F. JACC 2005;46:223-30
Aortic stenosis
Bicuspid aortic valve
May be associated with aortic coarctation
 If the woman is symptomatic, then
surgical correction should precede
pregnancy


– If without symptoms, consider treadmill test

Limited ability to augment CO
– Leads to increases in LV filling pressures
Siu SC, et al. Heart 2001;85:710-715
Aortic stenosis

Mild and moderate are generally tolerated

Severe AS can result in adverse outcomes
– Linked to AS severity1
– CHF incidence as high as 44% in moderate to
severe AS2
– Hospital admission rate 33%2
– Mortality rare1, 2
1. Silversides C, et al. AJC 2003;91:1386-9.
2. Hameed A, et al. JACC 2001;37:893-9.
Antepartum management of AS

Medical treatment limited to diuretics

If symptoms become refractory to medical
th
therapy,
b
balloon
ll
valvuloplasty
l l l t is
i
temporary option
Elkayam, U, Bitar, F. JACC 2005;46:223-30
Regurgitant valve lesions
MR and AR generally well tolerated even if
severe
– Probably from decrease in SVR
 Women with severe MR/AR BUT without
symptoms
t
DO NOT need
d surgery before
b f
conception
 Usual indications for surgery apply
 Even if symptomatic, pregnancy still
tolerated

Elkayam, U, Bitar, F. JACC 2005;46:223-30
Prosthetic heart valves
Pregnancy should be planned prior to
valve replacement
 Bio
Bio--prosthetic valves clearly have
advantages
 Risk of eventually needing another surgery

– ?degeneration more rapidly
Crawford MH, et al. Cradiology 2nd Ed. 2004:1549-58.
Prosthetic heart valves

Mechanical heart valves
– Offer long
long--term durability but need for anti
anti-coagulation
– Evidence to suggest increased adverse fetal
events

National guidelines for anticoagulation
vary from ACC/AHA to ACCP
Head CEG, Thorne SA. Postgrad Med J 2005;81:292-8.
Alex Trebek says:
It’s time for
Double Jeopardy…
And the category is
Anticoagulation in
pregnancy!
Anticoagulation in pregnancy



30% rate of fetal loss regardless of
method
Safest for mom’s valve is warfarin
throughout
Thrombotic risk
– Warfarin alone 4%
– Heparin, then warfarin 9%
– Heparin alone, up to 25%
Head CEG, Thorne SA. Postgrad Med J 2005;81:292-8.
Anticoagulation in pregnancy

Seems to be consensus although still not
decided
1. SC Heparin or LMWH for 12 weeks
2 Warfarin up to 36 weeks (INR 2
2.
2.5
2.55-3.0)
3 0)
3. Then, SC Heparin or LMWH for remainder
OR
1. SC Heparin or LMWH throughout
Elkayam, U, Bitar, F. JACC 2005;46:403-10.
Congenital heart disease in
pregnancy
Most common form of structural heart
disease affecting women of childbearing
age in North America
 Mortality

– Mainly related to pulmonary HTN

If surgically repaired, mortality for mom
and baby improve
Abbas, AE, et al. Int J Cardiol. 2005;98(2):179-89.
Left to right shunts

Atrial septal defect
– Usually well tolerated
– Can have increase in right to left shunt with
fall in SVR
– Higher risk of paradoxical embolization
Head CEG, Thorne SA. Postgrad Med J 2005;81:292-8.
Marfan syndrome








Population incidence of 1/5000
80% have cardiac involvement
Aortic rupture, dissection most common cause of
death
Dissection in pregnant women most often in 3rd
trimester or postpost-partum
Full echocardiogram
Shorten 2nd stage of labor
Ascending aorta > 4 cm, 10% dissection risk
Then CC-section recommended
European Heart journal 2003 (24); 767-768.
23 yo with Marfan syndrome 33 weeks
pregnant with ascending aorta measuring
3.6 cm and mitral valve prolapse with no
significant regurgitation.
regurgitation Her BP is
110/70mmHg.
 No medications and allowed to have
vaginal delivery with shortened 2nd stage
of labor with forceps

26 yo with Marfan syndrome and systemic
HTN with Type B aortic dissection 23
weeks pregnant. Ascending aorta
measures 4.2 cm by echocardiogram. BP
is 140/90mmHg.
 Developed
p Type
yp B dissection at 38 weeks
during first pregnancy and was “advised”
against becoming pregnant again.
 Started on labetalol and had a CC-section
delivery with no complications

Tetralogy of Fallot
Vsd
Hypertrophy of RV
Overriding aorta
Pulmonic stenosis
Tetralogy of Fallot

Most common cyanotic congenital heart
defect
– Up to 10% of CHD

If uncorrected, then fall in SVR makes
right to left shunt worse
– Lowest birth rates seen in those with
SpO2<85%
– Adverse events seen in series of 96
pregnancies in 44 patients
 Cardiac events: 32%
 Prematurity: 37%
Siu SC, et al. Heart 2001;85:710-715
 Birth rate: 43%
Presbitero P, et al. Circ 1994;89:2673-6.
Tetralogy of Fallot
Repair includes RVOT reconstruction and
VSD patch closure
 Pregnancy risk low in patients after repair
 However,
However need to evaluate:

– Residual shunt
– RVOT obstruction
– Pulmonary regurgitation
– RV systolic dysfunction
– Pulmonary HTN
Siu SC, et al. Heart 2001;85:710-715
Transposition of the great
arteries (TGA)

2nd most common cyanotic congenital
heart defect
– 5-7% of all congenital heart defects

Two types
– d-TGA, or complete transposition
– l-TGA, or congenitally corrected
Warnes, CA. JACC 2005;46:1-8.
Complete TGA

In a patient with transposition of the great arteries, the
circulations exist parallel to one another.
Congenitally corrected TGA

Pulmonary venous
blood reaches the
aorta via a
morphological
tricuspid valve and
RV Systemic venous
RV.
blood reaches the
pulmonary artery via
a morphological LV.
Complete TGA surgical
management
Congenital quiz time:
Contraindications to pregnancy
include all EXCEPT:
A.
B.
C.
D.
E.
27 yo with history of ASD closed surgically at
19 without complaints. Echo shows RA/RV
dilation with RVSP of over 70mmHg
25 yo with bicuspid AoV and mean gradient of
45
45mmHg
H
29 yo with systemic HTN, ejection click, and
radio--femoral delay noted on PE.
radio
26yo with LL--TGA with moderate TR and RVEF
50%
30 yo with MVP and severe MR, dilated LV and
LA, LVEF 35%, and NYHA FC IIII-III.
Pulmonary HTN
Not much controversy
 HIGH risk of peripartum maternal death

Condition
Primary PHTN
Mortality (%)
30
Eisenmenger
syndrome
Secondary PHTN
40--50
40
56
Neonatal mortality: 28%
 Case reports of treatment with IV
prostacyclin and inhaled nitric oxide

Siu SC, et al. Heart 2001;85:710-715
Head CEG, Thorne SA. Postgrad Med J 2005;81:292-8.
Congenital heart disease update
Literature review of 2,491 pregnancies
 Cardiac complications in 11%
 Most common complication was CHF (5%)
 Arrythmias most common in

– Fontan,
Fontan, TGA, and AVSD patients
Drenthen W, et al. JACC 2007;49:2303-11.
Congenital heart disease update

CHF most common in
– Eisenmenger, cyanotic CHD, and PAVSD

CV events (MI, death, CVA) most common
in

Overall, offspring mortality of 4%
– Eisenmenger, cyanotic CHD
– In industrialized world, expected <1%
Drenthen W, et al. JACC 2007;49:2303-11.
Systemic HTN and pregnancy

Systemic HTN affects 10
10--15% of all
pregnancies
– Leading cause of M&M for mom and baby
– Risk of IUGR and placental abruption

Classified into chronic, gestational, and
pre--eclampsia
pre
James PR, et al. Heart 2004;90:1499-1504.
Systemic HTN and pregnancy

Treat for SBP>160mmHg or DBP>110mmHg
–

Medications to use
–
–

Not too aggressive
Methyl--dopa
Methyl
dopa,, hydralazine
hydralazine,, labetalol
labetalol,, nifedipine
Women of childchild-bearing age who are on ACEACE-I and
ARB drug therapy need to be warned
Future risk of stroke, development of systemic
HTN, and ischemic heart disease
James PR, et al. Heart 2004;90:1499-1504.
Systemic HTN and future CHD
risk
Finnish study of over 10,000 women
Follow up available for 40 years for
women with hypertensive disorders during
pregnancy
 Any increase in BP during pregnancy
conferred increased risk of CV disease


– Even without known risk factors
Mannisto, T, et al. Circulation. 2013;127:681-690.
Systemic HTN and future CHD
risk
New onset isolated systolic or diastolic
HTN had assoc with increased CV disease
risk
 Extrapolating results to US population
would suggest >200,000 women have a
risk factor that is not well recognized
 Important to consider in primary
prevention

Mannisto, T, et al. Circulation. 2013;127:681-690.
Strokes spike in pregnant women,
new moms

Rates of stroke have jumped 54 percent from
1994--2007
1994

Data collection from Nationwide Inpatient
Sample

Rate of any stroke among antenatal
hospitalizations increased by 47% and among
postpartum hospitalizations by 83%
Kuklina, EV, et al. Stroke. 2011 Sep;42(9):2564-70.
Higher rates of stroke

Ages 25 to 34 were hospitalized for stroke more often

In 2006 to 2007, ≈32% and 53% of antenatal and
postpartum hospitalizations with stroke, respectively,
had concurrent hypertensive disorders or heart disease

Changes in the prevalence of these 2 conditions
explained almost all of the increase in stroke
Kuklina, EV, et al. Stroke. 2011 Sep;42(9):2564-70.
Peripartum cardiomyopathy
Onset of heart failure with no known cause
within the last month of pregnancy or 5 months
post--partum
post
1/4000 to 1/15,000
,
live births
Question of myocarditis as underlying etiology
Risk factors include:




– older maternal age, greater parity, black race and
twin gestations
Ray P, et al. Br J Anaesth. 2004;93(3):428-39.
Peripartum cardiomyopathy
Maternal mortality around 20%
 50% of patients will have persistent LV
systolic dysfunction

– Further
F th pregnancies
i contracontra
t -indicated
i di t d

Medical treatment as for any dilated
cardiomyopathy
Thorne, SA. Heart 2004;90:450-456.
32 yo woman immediately post-partum presents
with acute systolic CHF symptoms.
Echocardiogram shows dilated cardiomyopathy
with LVEF of 20%. She is started on medical
therapy and 6 months later her LVEF is 40%.

It is acceptable to become pregnant
g
again with no hesitation or concerns.
A. True.
B. False.
What if LVEF recovers?
LVEF
>50% 6(21)
(n=28)
6(21)
Decrease
LVEF at
F/U
no. (%)
4(14)
<50% 7(44)
(n=16)
4(25)
5(31)

HF
no.
(%)
> 20%
decrease
in LVEF
no. (%)
Death
no.
(%)
3(19)
0
Incidence of maternal complications following PPCM in
women with and without persistent LV dysfunction
Elkayam U, et al. NEJM 2001;344:1567-71.
Acute MI during pregnancy






2008 review of Medline search revealed 103
cases from 1995
1995--2005
Highest incidence occurred in antepartum
setting
Maternal mortality:
y 11%
Mean age of 33 years old
45% were smokers
Etiology
– 40% atherosclerosis
– 27%Dissection

Primary PCI preferred treatment
Roth A, Elkayam U. JACC. 2008 Jul 15;52(3):171-80.
Coronary dissection in a 39 yo 1 week
postpartum, after giving birth to triplets,
presenting with NSTEMI
Schroeder C, Stoler RC, Branning GB, Choi JW. BUMC Proceedings 2006.
6 weeks later
6 months later






37 year old G2P1 who is 6 weeks pregnant with
twins
Four weeks prior underwent PCI of the LAD with
drug eluting stent for unstable angina
Had PCI to a diagonal about 6 months prior also
with DES
First pregnancy complicated by placenta previa,
pre ecclampsia, and premature delivery
On clopidogrel and aspirin
Patient continued on dual antiantiplatelet agents until one week before
C section delivery and had no
complications
Review of CV disease in pregnancy





CV changes during pregnancy
– High volume, low resistant state
Pre--pregnancy counseling very important
Pre
Management requires multimulti-disciplinary
approach
Most common neonatal complications:
– Prematurity and IUGR
Most common presentation of heart disease
in pregnancy
– CHF and tachyarrhythmia