Download Cardiac Diseases in Pregnancy - University of Arkansas for Medical

February 18, 2005
Cardiac Diseases in Pregnancy
Ibrahim Elias Fahdi, MD
University of Arkansas for Medical Sciences
& Central Arkansas Veterans Healthcare System
Division of Cardiovascular Medicine
Objectives
• Normal Physiology during pregnancy
• Cardiac Testing
• Common cardiac problems
Cardio-circulatory changes during normal
pregnancy
parameter
Changes at various times (weeks)
5
12
20
24
32
38
HR
↑
↑↑↑
↑↑↑
↑↑↑
↑↑↑↑
↑↑↑↑
SBP
↔
↓
↓
↔
↑
↑↑
DBP
↔
↓
↓↓
↓
↔
↑↑
↑↑↑↑↑
↑↑↑↑↑↑
↑↑↑↑↑↑
↑↑↑↑↑
SV
↑
↑↑↑↑↑
CO
↑↑
↑↑↑↑↑↑
↑↑↑↑↑↑↑
↑↑↑↑↑↑↑
↑↑↑↑↑↑↑
↑↑↑↑↑↑↑
SVR
↓↓
↓↓↓↓↓
↓↓↓↓↓↓
↓↓↓↓↓↓
↓↓↓↓↓↓
↓↓↓↓↓
LV EF
↑
↑↑
↑↑
↑↑
↑
↑
↑ ≤ 5%; ↑↑ 6-10%; ↑↑↑ 11-15%; ↑↑↑↑ 16-20%; ↑↑↑↑↑ 21-30%; ↑↑↑↑↑↑ > 30%, ↑↑↑↑↑↑↑ > 40%.
“Our only hope is
if we all write a
letter to Santa…”
The Wall Street Journal
Changes in plasma volume, erythrocyte
volume, and hematocrit during pregnancy
• Plasma volume ↑ 50% (20-100%).
• “Physiologic anemia of
pregnancy”.
• Estrogen-mediated
stimulation of the RAS.
• Role of other hormones
– deoxycorticosterone,
prostaglandins, estrogen, prolactin,
placental lactogen, GH, ACTH,
ANP
From Pitkin RM, Nutritional support in obstetrics and gynecology. Clin Obstet Gynecol 1976;19:489.
Percent change in heart rate, stroke volume, and
cardiac output measured in the lateral position
throughout pregnancy compared with pregnancy
values
Modified from Robson SC, Hunter S, Boys RJ, Dunlop W. Serial study of factors influencing
changes in cardiac output during human pregnancy. Am J Physiol 1989;256:H1060-H1065
Cardio-circulatory changes during normal
pregnancy
parameter
Changes at various times (weeks)
5
12
20
24
32
38
HR
↑
↑↑↑
↑↑↑
↑↑↑
↑↑↑↑
↑↑↑↑
SBP
↔
↓
↓
↔
↑
↑↑
DBP
↔
↓
↓↓
↓
↔
↑↑
↑↑↑↑↑
↑↑↑↑↑↑
↑↑↑↑↑↑
↑↑↑↑↑
SV
↑
↑↑↑↑↑
CO
↑↑
↑↑↑↑↑↑
↑↑↑↑↑↑↑
↑↑↑↑↑↑↑
↑↑↑↑↑↑↑
↑↑↑↑↑↑↑
SVR
↓↓
↓↓↓↓↓
↓↓↓↓↓↓
↓↓↓↓↓↓
↓↓↓↓↓↓
↓↓↓↓↓
LV EF
↑
↑↑
↑↑
↑↑
↑
↑
↑ ≤ 5%; ↑↑ 6-10%; ↑↑↑ 11-15%; ↑↑↑↑ 16-20%; ↑↑↑↑↑ 21-30%; ↑↑↑↑↑↑ > 30%, ↑↑↑↑↑↑↑ > 40%.
Hemodynamic changes during labor
and delivery
•
•
•
•
Anxiety, pain, uterine contraction.
Oxygen consumption ↑ threefold.
↑ CO during labor (↑ SV and ↑ HR).
↑ SBP & DBP (especially 2nd stage)
• Those changes are influenced by the form
of anesthesia and analgesia.
Hemodynamic changes post partum
Increase in venous return
(relief of caval compression)
Blood shifting “auto-transfusion”
(from the contracting uterus to the
systemic circulation)
-
Blood loss
during delivery
Increase in effective blood volume
Substantial increase in LV filling pressure, SV and CO
Clinical deterioration
• HR and CO return to pre-labor values within 1 hour. MAP and SV within 24 hours.
• Hemodynamic adaptation persists post partum and return to pre-pregnancy values
within 12-24 weeks after delivery.
Before conception
History
Exercise capacity
Current or past evidence of HF
Associated arrhythmias
Physical exam
Cardiac Hemodynamics
Severity of heart disease, PA pressures
Echo, MRI.
Exercise testing
Useful if the history is inadequate to allow assessment of functional capacity
During pregnancy
Evaluate once each trimester and whenever there is change in symptoms
Multidisciplinary approach, Fetal Echo
During Labor & Delivery
Multidisciplinary approach (Obstetrician, Cardiologist, Anesthesiologist)
Tailor management to specific needs
Reimold, S. C. et al. N Engl J Med 2003;349:52-59
High-risk pregnancy
• Pulmonary HTN and Eisenmenger’s
syndrome.
• Symptomatic obstructive cardiac lesions:
– AS, PS, uncorrected coarctation of the aorta.
• Marfan’s Syndrome with dilated aortic root.
• Systemic ventricular dysfunction (LVEF <
40%).
• Severe cyanotic heart disease.
• Patients with prosthetic valves.
• Significant uncorrected CHD.
Contraindications to Pregnancy
Lesion
Maternal
death rate (%)
• Severe Pulmonary Hypertension
50
• Severe obstructive lesions:
AS,PS, HOCM, Coarctation.
17
• Systemic Ventricular Dysfunction,
NYHA class III or IV
7
Pregnancy Outcomes
• The prevalence of clinically
significant maternal heart disease
is low (<1%)1.
• Its presence increases the risk of
adverse maternal, fetal, and
neonatal outcomes2.
1.
2.
Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with
heart disease. Circulation 2001;104:515-521.
Siu SC, Colman JM, Sorensen S, et al. Adverse neonatal and cardiac outcomes are more common in
pregnant women with cardiac disease. Circulation 2002;105:2179-2184.
CARPREG
• Cardiac disease in pregnancy;
prospectively enrolled 563 consecutive
pregnant women with heart disease
• Outcomes were determined in 599
pregnancies not ending with miscarriage
Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with
heart disease. Circulation 2001;104:515-521.
Adverse maternal cardiac events
Primary cardiac events:
Secondary adverse cardiac events:
80
Cardiac event rate (%
percentage)
1. Pulmonary edema.
2. Sustained brady- or tachy- arhythmias
requiring therapy.
3. Stroke.
4. Cardiac arrest.
5. Death
62%
1. Worsening of NYHA class by > 2 classes.
2. Need for urgent invasive cardiac procedure
70
60
50
27%
40
30
Predicetd
Derivation
Validation
4%
20
10
0
(percutaneous cardiac valvuloplasty, permanent pacing).
Predictors of primary cardiac events
0
1
>1
Number of predictors
Odds ratio (95% CI)
p
1. Prior cardiac event (HF, TIA or stroke) or arrhythmia.
6 (3-14)
<0.001
2. Baseline NYHA class > II or cyanosis.
6 (2-22)
0,009
3. Left heart obstruction (MVA < 2cm2, AVA < 1.5 cm2, or peak LVOT gradient > 30 mmHg).
6 (3-14)
<0.001
4. Reduced systemic ventricular systolic function (EF < 40%)
11 (4-34)
<0.001
N.B.: There was no association between the type of delivery and peripartum cardiac event rate (3% vs. 4%, P=0.46).
Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521.
Adverse neonatal events
4
Event rate (% percentage)
Neonatal events:
1. Premature birth
2. Small-for-gestational-age birth weight.
3. Respiratory distress.
4. Inter-ventricular hemorrhage.
5. And death.
3.5
3
2.5
2
0
1.5
>1
1
0.5
0
0
>1
Risk factors
Predictors of primary cardiac events
Odds ratio (95% CI)
P
1. Abnormal functional capacity (NYHA class ≥ II or cyanosis)
3 (1.1-6.1)
0.035
2. Use of anticoagulant drugs throughout pregnancy.
3 (1.4-8.2)
0,0093
3. Smoking during pregnancy.
4. Multiple gestation.
5. Left heart obstruction
6. Women > 35 years old or < 20 years old.
2 (1.3-13.9
0.0045
22 (6-85)
2 (1.01-2.9)
-
<0.001
0.044
-
N.B.:in the 6 pregnancies in which the mother received warfarin during all (n=2) or part of pregnancy
(n=4), embryopathy was not observed in this small series.
Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104:515-521.
Cardiac Tests Performed 1
• Doppler echocardiography
• Stress testing
• Radiation of the embryo
– Age o to 10 days: no effect or resorption
– Age 10 to 50 days: teratogenic effects
– Age 50 to delivery
• Intrauterine growth retardation
• Central nervous system abnormalities
• Increased incidence of childhood cancer or
leukemia
Cardiac Tests Performed 2
• Routine chest radiography delivers 20
m.rads
• Standard fluoroscopy delivers 1-2
rads/min
• Current recommendation
– >5 rads: very low risk
– 5-10 rads: counseling for low risk
– 10-15 rads during 1st 6 weeks: individual
– >15 rads: termination pf pregnancy
Colletti PM, Lee K: Cardiac Problem in Pregnancy.3rd ed. New York, Wiley Liss, 1998, pp 33-36
Cardiac Tests Performed 3
• Magnetic Resonance Imaging
• Pulmonary Artery Catheterization: Great
help in managing high risk patient during
pregnancy, labor and delivery
• Cardiac Catheterization
– Can be done
Pulmonary hypertension as a risk of adverse
outcome
Pulmonary hypertension
(Eisenmenger Syndrome)
Increased rate of adverse maternal events
Up to 30-40% (↑ PVR)
When systolic PAP > 75% systemic pressure
↑ intravascular volume
HF
(CO limited by Pulmonary vascular disease and Ventricular dysfunction)
↓ SVR (after 1st trimester)
↑R-L Shunt
Cyanosis
Exacerbated during labor and delivery
Bed rest (2nd trimester), O2 (if helpful), ? Anticoagulation,
Cesarian section, invasive monitoring, early ambulation
Aortic stenosis
• Severe AS is poorly tolerated.
– AVA < 0.7 cm2, Mean PG > 50 mmHg.
– Mortality up to 17%.
• Symptomatic patients or Mean gradient > 50
mmHg
• → Delay conception until after surgical or
interventional correction.
• Consider balloon valvuloplasty, Ross
procedure, tissue valve (no need for
anticoagulation).
• Symptomatic patients before end of 1st
trimester
• Terminate pregnancy.
• Β-Blockade, Bed rest.
• Palliative aortic balloon valvuloplasty or
AVR.
• Early Delivery.
Reimold, S. C. et al. N Engl J Med 2003;349:52-59
Hameed A, et al. The effects of valvular heart
disease on maternal and fetal outcome of
pregnancy. J Am Coll Cardiol 2001;37:893-9.
Prosthetic valves and
pregnancy
Anticoagulation
Warfarin vs. Heparin
Warfarin
Heparin
• Crosses the placenta.
• ↑early abortion, prematurity,
and embryopathy when used in
1st trimester (6th–12th weeks).
• CNS & Eye abnormalities (2nd
& 3rd trimester).
• Bleeding in the fetus
(especially at delivery)
– Should be stopped before
delivery.
• Does not cross the placenta
• No teratogenicity
• No fetal bleeding
• Twice daily SC injection
• Risk of osteoporosis
– <2% symptomatic fractures.
– but 30% decrease in bone density.
• Risk for thrombocytopenia
• ↑↑ Risk of thrombosis
“warfarin embryopathy”: Nasal hypoplasia, Bone epiphysis, optic atrophy,
blindness, seizures.
Overall risk around 5%. Decreases with the use of UFH in the first 3 months
Dose-dependent Fetal Complications of warfarin in
pregnant women with Mechanical Heart Valves
Outcome of pregnancies
WARFARIN
DOSE (MG)
≤5
Healthy fetuses
28
5/33 (15%)
• 4 SA
• 27 FT
•1 PR
>5
Fetal
complications
Total
33
• 1 GR
•0 WE (0%)
3 FT
22/25 (88%)
25
• 2 WE (9%)
• 18 SA
• 1 SB
• 1 VSD
Total
31
27
58
FT = full term, GR = growth retardation; PR = preterm; SA = spontaneous abortion; SB =
still birth; WE = warfarin embryopathy
Vitale N, et al. J Am Coll Cardiol 1999;33:1637-41.
Unfractionated Heparin
•
4X higher incidence of Thrombo-embolism
during pregnancy than oral anticoagulants1.
1.
•
Hanania G, et al. pregnancy in patients with valvular prosthesisretrospective cooperative study in France (155 Cases). J Arch Mal Coeur
Vaiss 1994;87:429-437.
Failure of adjusted dose SC heparin to prevent
thrombo-embolic phenomena in pregnant
women (n= 40) with mechanical valve prosthesis.
– Adjusted doses of SC heparin does not improve
fetal outcome and increases maternal mortality2.
2. Salazare E, et al. Filure of adjusted dose heparin to prevent thromboembolisc
phenomena in pregnant patients with mechanical cardiac valve prosthesis. J Am
Coll Cardiol 1996;1698-1703.
Frequency of fetal and maternal complications according to the
anticoagulation regimen used during pregnancy in women with
mechanical heart valve prosthesis.
Adapted from Chen et al. (976 women, 1234 pregnancies)
Anticoagulation regimen
Vitamin K antagonist
throughout pregnancy
Embryopathy
(%)
Spontaneous
abortion (%)
Thromboembolic
complications
(%)
Maternal death
(%)
6.4
25
31/788 (3.9%)
10/561 (1.8%)
Heparin throughout pregnancy
0
24
7/21 (33%)
3/20 (15%)
• Low dose
0
20
60
40
• Adjusted dose
0
25
25
6.7
3.4
25
21/229 (9.2%)
7/167 (4.2%)
Heparin during first trimester,
then vitamin K antagonists
(with or without heparin before
delivery)
Chan WS. What is the optimal management of pregnant women with valvular heart disease in pregnancy?
Haemostasis 1999,29 suppl S1:105-6
Low-dose ASA
• The additional use of low-dose aspirin should be
considered, particularly in
•
•
•
•
•
Women with high-risk valves.
Patients with cyanosis.
Patients with intra-cardiac shunts.
Women with previous TIAs and/or strokes.
And women with atrial fibrillation.
Chan WS. What is the optimal management of pregnant women with valvular heart disease in
pregnancy? Haemostasis 1999,29 suppl S1:105-6
LMWH
•
•
•
•
Do not cross the placenta.
Do not require frequent PTT monitoring
and have a longer half-life than UFH.
The data to support the use of LMWH, however, is not yet
available.
• A successful use of LMWH was reported in small number of
patients and more information is required before LMWH can be
recommended for anticoagulation in a patient with a prosthetic
valve during pregnancy1.
• Recently, two cases of LMWH treatment failure resulting in
thrombosed prosthetic heart valves were reported in 20002.
• LMWH should not be recommended at the present time in
patients with heart valve prostheses during pregnancy.
1.
2.
Elkayam U. Pregnancy through a prosthetic heart valve. J Am Coll Cardiol 1999;33:1642-5.
Lev Rano, Kamer A, Gurevitch J, Shapira, Mohr R. Low-molecular weight heparin for prosthetic
heart valves: treatment failure. Ann Thoracic Surg 2000; 69: 264-5.
Mechanical Valves and
Anticoagulation during Pregnancy
• Heparin may not prevent valve thrombosis:
?how much ?route.
• Adequate anticoagulation difficult.
• Heparin can produce osteoporosis.
• Little data regarding LMWH.
• Warfarin can cause embryopathy.
• Baby ASA safe + probably beneficial.
1-4% mortality in pregnant women with mechanical
valve prosthesis, Whatever the anticoagulation
regimen.
No Ideal Solution
Suggested algorithm for the management of
anticoagulation in patients with mechanical prosthetic
heart valves during pregnancy
Pregnancy in patients with
prosthetic heart valves
Higher risk
First-generation prosthesis
(e.g Starr-Edwards, Bjork- Shiley)
In the mitral position
Coumadin to INR
3.0-4.5 for 36
weeks followed by
IV heparin to
aPTT of > 2.5-3.5
Lower risk
Second-generation prosthesis
(e.g., St Jude Medical, Medtronic Hall)
And any mechanical prosthesis in the
aortic position
SC or IV (better)
heparin-(aPTT 2.5-3.5)
for 12 weeks
SC Heparin
(aPTT 2.0-3.0)
for 12 weeks
Coumadin
(INR 3.0-4.5)
to 36th week
Coumadin
(INR 2.5-3.0)
to 36th week
IV heparin
(aPTT > 2.5)
SC Heparin
(aPTT 2.0-3.0)
Braunwald textbook of cardiovascular medicine, 6th edition
SC heparin
(aPTT 2.0-3.0)
Throughout
pregnancy
1-4% mortality in
pregnant women with
mechanical valve
prosthesis, Whatever
the anticoagulation
regimen.
Mode of delivery
Vaginal delivery
• With facilitated second stage
is preferred & safe
• Invasive hemodynamic
monitoring only in:
– Severe valve stenosis
– Recent heart failure.
Cesarean section
• Avoids physical stress of labor
• but not free from hemodynamic
consequences.
• Indications in CHD only for:
– Obstetric reasons.
– Therapeutic anticoagulation with
coumadin at onset pf labor.
– Pulmonary hypertension.
– Unstable aortic lesion with risk of
dissection.
– Severe obstructive lesions
– Severe cyanotic heart disease
– Pulmonary HTN.
Breast-feeding
• Can be encouraged in women
taking anticoagulants.
• Heparin is not secreted in
breast milk
• and the amount of warfarin is
low.
1.
2.
3.
Hameed A et al. J Am Coll Cardiol 2001;37:893–9.
Elkayam U, et al. New Engl J Med 2001;344:1567–71.
Bozkurt B, et al. J Am Coll Cardiol 1999;34:177–80.
Endocarditis prophylaxis
• Antibiotic prophylaxis at the time of delivery is not recommended for
patients expected to have uncomplicated vaginal delivery or
cesarian section, unless clinically overt infection is present 1,2
• Patients at high risk for endocarditis may receive antibiotics at the
discretion of their physician2:
– Those with prosthetic heart valves.
– Previous IE.
Antibiotics for prophylaxis against endocarditis
Ampicillin
No major adverse effects
Given along with gentamicin to
high-risk patients to prevent IE
B
2 gr IV or IM within 30 min before
delivery.
And 1 gr PO, IV or IM 6 hrs later.
Vancomycine
No major adverse effects
Given along with gentamicin to
high-risk patients to prevent IE
Cm
I gr IV over 1-2 hours, given 30 min
before delivery.
Gentamicin
No major adverse effects
Given along with Ampicilline or
Gentamicin to high-risk patients
to prevent IE
C
1.5 mg/kg within 30 min before
delivery (max 120 mg)
1 Sugrue D, Troy P, McDonald D. Antibiotic prophylaxis against infective endocarditis after normal delivery -- is it necessary? Br Heart J 1980;44:499-502.
2 Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA 1997;277:1794-1801.
Pregnancy and CHD
Conclusions
• Most women with heart disease can have
a pregnancy proper care.
• Pre-pregnancy evaluation mandatory.
• High-risk cases benefit from combined
high-risk OB and cardiac care in the same
center.
Questions