Document 6428053

Pregnancy in Patients with Prosthetic Heart
Valves*
Asher Buxbaum, M.D.; Maurice M. Aygen, M.D.; Wehbi Shuhin, M.D.;
1Mor1.i~J. Levy, M.D., F.C.C.P.; and Benjamen Ekerling, M.D.
Five pregnancies in two patients with prosthetic milral valves resulted in three
spontaneous abortions, one missed abortion and one live baby. The incidence of
fetal mortality in 50 pregnancies in 43 patients with prosthetic valves reported in
the literature was 28 percent. One mother whose pregnancy was complicated by
thromboembolism, died following cesarean section. The use of oral anticoagulants augmented considerably the risk to the fetus. Omission of the treatment on
the other hand, increased the danger of systemic embolization to the mother.
omen with prosthetic heart valves can tolerate
pregnancy and delivery. 1-1W o w e v e r , there
is an increased risk to the motherl+-'D and the
child.*"-" Among various factors, anticoagulants
appear to play an important role in determining the
outcome of pregnancy. In this presentation we add
the outcome of five pregnancies in two patients
with prosthetic rnitral valves to those reported in
the literature and correlate the incidence of fetal
and maternal morbidity and mortality to the use or
omission of anticoagulants.
The patient was a 23-year-old nlarried woman without any
history of rheumatic fever. At the age of 19 heart disease was
discovered and she began to receive a digitalis preparation
and diuretics because of shortness of breath on moderate
exertion. One year later she was referred to Beilinson Medical Center for evaluation of her hemodynamic state. Clinical
catheterization and angiocardiographic studies established
the presence of severe mitral regurgitation, moderate mitral
stenosis, mild aortic regurgitation and puln~onary hypertension (Table 1 ). On July 10, 1966, her mitral valve was
replaced by a No. 3 Starr-Edwards prosthetic valve. The
operation and the postoperative period were uneventful. She
was discharged on digoxin, 0.25 mg daily, warfarin sodium
and monthly injections of benzathin penicillin. Six months
after her discharge fro111 the hospital, the patient became
pregnant, but spontaneous abortion occurred in the third
month. During the following year the patient felt well with
almost no limitation of her activity and digoxin was discon*From the Cardiopulmonary, Thoracic-Cardiovascular Surgery and Obstetrics deparhnents, Beilinson hledical Center,
Petah-Tiqva, and Tel-Aviv University School of Medicine.
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tinued. During the same year, a second spontaneous abortion
occurred in the second month of pregnancy. In November
1967 postoperative right heart catheterization showed an
increase in cardiac output and reduction in pulmonary capillary and pulmonary artery pressures from the preoperative
levels (Table 1 ). In 1968 her third pregnancy terminated
with spontaneous abortion in the first trimester. When she
was seen in our clinic in January 1969, the patient was in the
second month of her fourth pregnancy. The patient again
desired to continue with the pregnancy, even though the
dangers involved were fully explained to her. Because of
previous episodes of spontaneous abortion in the first trimester, she was hospitalized for evaluation and possible
change of her medication. Initially, warfarin sodium (Coumadin) was discontinued and she was given injections of
heparin. This regimen, however, seemed to be too difficult to
be followed for the whole period of her pregnancy and a
week later phenindione was started and the heparin injections discontinued. Following her discharge and throughout
her pregnancy the prothrombin time was maintained within
the range of 20 percent to 30 percent of normal. No complications occurred during the pregnancy and her general and
cardiac status remained good during the whole period. Two
weeks before term the patient was hospitalized in the obstetrical ward. Phenindione was then discontinued and the clotting time was maintained at two to three times the normal
level with intramuscular heparin injections. On September
23, 1969, the patient spontaneously delivered a normal baby
boy. The baby's birth weight was 3,520 gm. Bleeding and
coagulation times of the infant were normal. The patient had
an increased blood loss during delivery and for a few days
afterwards, and it was necessary to administer three units of
whole blood to keep the hemoglobin concentration around 10
gm percent. Warfarin sodium was started on the fifth postpartun1 day and heparin was discontinued on the seventh day
after delivery when the prothrombin time had reached 25
percent. The infant was circumcised when he was eight days
old, with no untoward effects. h.iother and child have been
doing well during the 12 months since delivery.
BUXBAUM ET AL
Table 1-Hernodynamic
C u e No. I
Preop
Postop
16 months
Caae N o . 2
Preop
Post 01)
14 months
Data before and after Mitral Valve Replacement.
B .4
PC
mean
(mm Hg)
PA
mean
(mm Hg)
RV
s/d
(mm Hg)
RA
mean
(mm Hg)
s/d
(mm Hg)
24
32
40/3
4
90/60
17
22
30/9
9
120/70
23
70
104/27
20
120/80
8
21
36/2
2
120/80
LV
s/d
(mm Hn)
CO
(l/min)
105/6
4.9
115/18
3.2
Abhreviat ions: P C = pulmonary capillary; PA ==pulmonaryartery; RV =right ventricle; K.4 =right atrium; BA =brachial artery;
LV =left v~ntricle;CO cardiac output.
The patient was a 38-year-old woman who had had rheumatic fever at the age of 16. She had had no significant
cardiac symptoms until the age of 30, when following a
normal delivery, aided by low forceps, she began to complain
of progressive exercise intolerance. In spite of intensive
medical therapy, she developed chronic congestive heart
failure with ascites, and she was severely incapacitated. The
physical examination and hemodynamic studies revealed severe combined mitral valve disease and markedly elevated
pulmonary artery pressure (Table 1 ) . In January 1964 she
underwent open heart surgery and the mitral valve was
replaced by a Starr-Edwards valve. After the operation the
signs of pulmonary hypertension disappeared, the liver regressed and her exercise tolerance improved markedly. Digitalis and diuretic therapy were gradually discontinued and
she was maintained on treatment with warfarin sodium
(Coumadin). Her menstrual periods, which had been absent
for more than two years prior to the operation, reappeared.
Postoperative right heart catheterization showed remarkable
improvement in hemdynamics (Table 1).
In April 1968 she reported to our clinic in the third month
of pregnancy. In accord with the desire of the patient, it was
decided to continue the pregnancy without stopping the
anticoagulants. In the sixth month the obstetrician noted a
lack of progress in the pregnancy, which according to his
estimate, had not progressed beyond the third month. The
Laudon procedure was used to induce abortion without
success. Two months later curettage was performed without
complications, and her general and cardiac status remained
n d .
In a series of 17,128 pregnancies, reported by
Gilbert and co-workers," the fetal mortality among
noncardiac pregnant women was 1.6 percent,
among cardiac patients it was 3.2 percent and
among cardiac patients with failure it was 10.5
percent. In 50 pregnancies in 43 patients with
prosthetic valves reported in the literature, including those in our two patients, the fetal mortality
was 28 percent. In these patients the degree of
hemodynamic disorder and the functional incapacity, as well as the anticoagulants per se, may have a
cumulative effect on the outcome of the pregnancy.
QuickZGnd Kraus and associates24 administered
large doses of cournarins to pregnant animals and
observed very high incidence of fetal hemorrhage
and death. On the other hand Hirsh and col1eagueslVound no fetal hemorrhage in rabbits,
when they stopped the warfarin a few days before
term or when the delivery was performed by
cesarean section. On the basis of these experiments
and from clinical observations they concluded that
oral anticoagulants may not increase the risk of
fetal hemorrhage unless continued until term. Considering that the teratogenic effect of drugs passing
the placental membranes are highest in the early
period of fetal development, the same author also
advised substitution of heparin for oral anticoagulants in the first 12 weeks of gestation.
The fetal morbidity and mortality in 50 pregnancies in 43 patients with prosthetic valves in relation
to anticoagulants are summarized In Table 2. Nineteen patients received oral anticoagulants of the
coumarin and indandione group throughout the
pregnancy and in the perinatal period. There were
five spontaneous abortions and five stillbirths in this
group. In addition, two children died a few hours
after birth. Autopsy in a stillborn and in a postpartum death showed multiple hemorrhages in the
lungs, brain, cerebellum, liver and thymus.'"
In 11 patients the oral anticoagulants were replaced by heparin at various stages of pregnancy
(oral and heparin). Two children in this group
were born with malformation^.'"."^ It should be
pointed out that all patients in this group received
oral anticoagulants in the first two months of
pregnancy. The single child loss of the group
occurred in a patient whose pregnancy was complicated by cerebral embolization, congestive heart
failure and oliguria.17 Cesarean section was performed in the 30th week of gestation. The child's
weight was 680 gm; and died 9 hours after delivery.
CHEST, VOL. 59, NO. 6, JUNE 1971
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641
PREGNANCY IN PATIENTS WITH PROSTHETIC HEART VALVES
Table 2--Fetal Morbidity and Mortality in Relation t o Anticoagulants in 43 Patients ( 5 0 Pregnancier)
with Prosthetic Hemt Valoes.
Anticoagulants
Oral
Oral and Heparin
Interrupted
None
Unknown
Total
Number of
Pregnancies
A
M
A+M
Abortion and
Stillbirth
A
M
A+M
Died in
24 Hours
A
M'
-
15
1
-
3
10
4
2
2
1
-
15
33
2
-
3
1
4
4
9
1
-
-
-
-
1
2
9
-
2
1
-
3
A
Malformations
A
M
-
-
-
2
-
-
-
2
A
Abbreviations: A=prosthetic aortic valve; M =prosthetic mitral valve; A+M =prosthetic aortic and mitral valves.
The outcome of eight pregnancies in patients in
whom the anticoagulant treatment was interrupted
during pregnancy, was live babies. Similarly, no
fetal morbidity or mortality was encountered in six
pregnant women who received none of the anticoagulants throughout pregnancy.
In six pregnancies reported in the literature it
was not possible to determine whether or not they
received anticoagulants.
The fetal morbidity and mortality was confined
to the pregnancies in patients with prosthetic mitral
valves. The difference may be due to the fact that
few patients with prosthetic aortic valves received
anticoagulants. However, a hemodynamic factor
cannot be excluded. In postoperative hemodynamic
studies in patients with prosthetic mitral valves,
Hultgreen and associates27 and others28 found low
resting cardiac output and a subnormal output
response to exercise. In contrast, patients with
prosthetic aortic valves had normal output at rest
and on exerci~e.~*:%O
Failure to augment the cardiac output to satisfy the increased metabolic demands of the fetus may be a factor in causing fetal
death in advanced months of pregnancy, but it is
unlikely to be a cause for the abortions in the early
months. Six of the fetal deaths occurred in the first
trimester.
The maternal morbidity and mortality in 50
pregnancies are summarized in Table 3.
Table 3-Maternal
Maternal bleeding requiring transfusion in the
postpartum period was reported in three patients
2 e
receiving heparin, including our case."'"
patient on oral anticoagulants was hospitalized
twice during pregnancy for vaginal bleeding.:':j
Systemic embolization occurred in three out of 30
pregnancies while the patients were receiving anticoagulants. From the literature it is impossible to
determine whether or not they received adequate
therapy. The highest incidence of thromboembolic
phenomena occurred in patients in whom the anticoagulant therapy was interrupted during pregnancy.
The only case of maternal death in a patient with
a prosthetic valve was reported by Bennett and
Oakley.17 Their patient had episodes of cerebral
embolization in the first month of pregnancy and
developed severe congestive circulatory failure and
oliguria requiring peritoneal dialysis in the eighth
month. She died after cesarean section and subtotal
hysterectomy. A large thrombus, which immobilized the mitral valve, was found at autopsy. This
patient received oral anticoagulants in the first eight
weeks of pregnancy and heparin until term.
The data demonstrated that oral anticoagulants
augmented considerably the fetal mortality. Substitution of heparin in the perinatal period reduced
the risk. The effectiveness of heparin in modifying
the incidence of fetal morbidity and mortality,
Morbidity and Mortality in Relation t o Anticoagulants in 43 Patienb ( 5 0 Pregnancies)
with Prosthetic Heart Valves.
Anticoagulants
Oral
Oral and Heparin
Interrrlptctl
None
I'nknown
A
Number of
1'rt.gnancies
M
A+M
3
15
1
4
4
10
4
3
2
2
1
A
-
1
Bleeding
A
M
-
Systemic
Emboliration
A
M
I
3
-
2
-
1
-
3
-
1
-
-
Death
A
M
-
-
--
Total
15
33
2
,il,t)l.cviationx: as in Tal)lc, 2.
CHEST, VOL. 59, NO. 6, JUNE 1971
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-
4
3
4
-
1
-
-
1
BUXBAUM ET AL
when given to the mother in the first trimester of
pregnancy remains to be determined.
Anticoagulants were not effective or adequate to
eliminate completely the risk of thromboembolism.
However the patients who stopped the treatment
during pregnancy carried a higher risk than those
who continued and than those who never received
anticoagulants.
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valve. Obstet Gynec 27:508-510, 1966
3 Johnson AS, Meyers MP, Eckhous AS, et al: Successful
pregnancies in patients with ~rosthetic mitral valves.
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5 Starke H, Dann M, Kittle C F : Successful pregnancy
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6 McDonald TW, Dilworth EE: Successfi~lpregnancy in a
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7 Turner RWO, Kitchin AH: Pregnancy after mitral valve
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12 Hart PG: Birth of a full-term healthy child fro111a mother
with a Starr-Edwards prosthesis in the ~nitral orifice.
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13 Barnard PM, Heydenrych JJ, Lombard BG: hiitral valve
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24 Kraus AP, Perlow S, Singer K: Danger of Dicumarol
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26 Kerber IF, Warr OS 111, Richardson C: Pregnancy in a
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27 Hultgreen H, Hubis H, Shumway N : Cardiac function
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28 McHenry hlM, Smeloff EA, Davey TB, et al: Hemodynamic results with full-flow orifice prosthetic valves.
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Reprint requests: Dr. Aygen. Beilinson Hospital, Petah Tiqva,
Israel.
Erratum
In the article "Advantages of the Beall Valve Prosthesis"
by Vogel e t a1 (Chest 59:249, 1871) figures 1 and 5
were reversed.
CHEST, VOL. 59, NO. 6, JUNE 1971
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