Introduction
Kawasaki disease (KD), first described in 1967, is a systemic vasculitis of unknown
cause.
1
It is an important
cause of cardiac diseases in children aged younger than five years.
2
KD is an autoimmune disorder whose
clinical features include high fever, exanthema, conjunctivitis, cervical
linfadenopathy and peripheral edema. Laboratory tests are compatible with acute
inflammatory condition.
KD predominantly affects the coronary arteries, which is the most important clinical
manifestation of the disease, varying from dilation and stenosis to aneurysm
(incidence of 5% in patients with adequate treatment, and 25% in untreated
patients). Giant coronary artery aneurysms (CAAs), i.e., CAAs with diameters > 8
mm, are associated with increased risk of thrombosis, acute myocardial infarction
(AMI) and sudden death.
2
Lack of diagnosis and treatment of KD at its acute phase during childhood contributes
to increased prevalence of pregnant women with vascular sequelae of KD.
3
Management of these patients has not
been established, especially in symptomatic patients and, in existing literature,
premature labor has been performed in these cases. There are no Brazilian reports
on
the theme, which are more commonly found in the American and Japanese
literature.
The aim of this study is to describe a successful management of a patient with giant
CAA, sequela of KD with thrombotic complication, from the first trimester of
pregnancy until term birth.
Case report
A 32-year old patient was admitted to the emergency care at week nine of first
pregnancy, with dyspnea and slight, precordial pain during great efforts, of
short duration and well tolerated. The patient had a history of ST-elevation
myocardial infarction of inferior wall at the age of 30, with giant aneurysms
and coronary artery thrombosis evidenced by coronary angiography (Figure 1C and 1D).
The patient underwent coronary computed tomography angiography,
which confirmed the previous findings, with evidence of coronary artery ectasia
with multiple aneurysmatic dilatations and mural thrombus (Figure 2). The patient
received the diagnosis of KD and was
referred to outpatient follow-up. At the occasion, the patient was using
simvastatin, clopidogrel, atenolol and acetylsalicylic acid (ASA). At physical
examination on admission, the patient was eupneic, with blood pressure of 110/60
mmHg, heart rate of 80 bpm, normal heart sounds without murmurs, normal
pulmonary auscultation, abdomen free of abnormal signs, and normal pulse rate.
Regarding complementary tests, electrocardiography showed sinus rhythm with
diffuse ventricular repolarization; transthoracic echocardiogram is depicted in
Figure 1A and 1B.
Figure 1
(A and B) Echocardiography: ejection fraction 68%; left atrium 35 mm;
septum 8mm; posterior wall 8mm; left ventricular diastolic diameter
45mm; left ventricular systolic diameter 30 mm; PSAP 40 mmHg.
Dilatation of left coronary artery (7 mm). Left ventricle with
preserved systolic function and myocardial thickness, with no
changes in segmental wall motion. (C and D) Cardiac catheterization
(10/2013): coronary artery ectasia. Dominant coronary with 50%
proximal, eccentric tubular lesion and coronary thrombosis; left
coronary artery trunk with aneurysmatic dilatation at the distal
third; anterior descending artery with ectasia at the proximal
third, without obstructive lesions. Circumflex artery with proximal
ectasia, without obstructive lesions.
Figure 2
Coronary computed tomography angiography showed aneurysm at the
distal third of the left coronary artery trunk (9mm) and anterior
descending artery ostium (9.5 mm); circumflex artery with ectasia at
the ostium (3.7 mm); marginal branch 2 with aneurysm at the distal
segment; right coronary artery with saccular aneurysm (9.8 mm at the
greatest diameter), mural thrombus and small regions of
calcification. Total score of 23.81 (Agaston) and 38.59 (Volume).
MT: main trunk of the left coronary artery; DA: anterior descending
artery; DB: diagonal branch; CA: circumflex artery; M1: left
marginal artery; M2: second marginal branch of circumflex artery;
RCA: right coronary artery; LA: left atrium; Ao: aorta
Despite recommendations received in outpatient visits on contraindications for
pregnancy, the patient got pregnant, and a close monitoring of the patient was
started. A daily dose of 100 mg of ASA, 60 mg of propranolol and 40 mg of
enoxaparin were prescribed, and routine obstetric exams showed normal fetal
vital signs. After 29 weeks of pregnancy, the patient had progressive worsening
of cardiac function to New York Heart Association (NYHA) class III, with daily,
atypical palpitations, which caused the patient to get a sick leave to rest at
home.
During the week 34, the patient had diffuse chest pain, dyspnea and uterine
contractions. The patient was then hospitalized for a rest and adjustment of
medication. Obstetric examination revealed irregular, weak contractions, fundal
height of 33 cm, impenetrable cervix, a single fetus in longitudinal position,
cephalic presentation, regular heart beat at 128 bpm. Fetal assessment was
performed by fetal biophysical profile and normal doppler velocimetry of
umbilical arteries. Estimated fetal weight was adequate (percentile of Hadlock
growth curve). There was a marked improvement in clinical and obstetric
conditions as result of adjustments in propranolol (80 mg/day orally) and
enoxaparin (60 mg/2x day subcutaneously) doses, as well as administration of
sublingual nitrate (only if needed) and vaginal tablets of natural micronized
progesterone (200 mg/2x day). There were no changes in electrocardiographic or
echocardiographic patterns during hospitalization. At week 37, cesarean section
and tubal ligation were indicated. The procedure was successfully performed by
the Central Institute obstetric staff at the Heart Institute (InCor) of the
General Hospital of the University of Sao Paulo Medical School. Newborn was born
healthy, weight 2,860 g, appropriate for gestational age, Apgar score of 9 and
10 at fifth and tenth minute of life, respectively. Tubal ligation was performed
following delivery, with previous consent of the spouse. Enoxaparin was
discontinued 12 hours before and restarted 24 hours after cesarean section.
Forty-eight hours later, warfarin was prescribed and readjusted until the
prothrombin international normalized ratio (INR) was 2; at this time, enoxaparin
was suspended and the patient was discharged. At the clinical visit 60 days
thereafter, the patient was asymptomatic, breast feeding and using warfarin (INR
= 2) and ASA (100 mg/d).
Discussion
In the present case, strategies for prevention of complications of giant CAAs
secondary to KD and acute infarction were successful in terms of maternal-fetal
health.
Preventive therapy was planned during patient’s first medical visit at week 9 of
pregnancy. The strategy consisting of outpatient follow-up, hospitalization and
delivery with interventional support at a cardiology hospital was chosen because of
patient instability. However, such procedure is not considered routine in the
literature in symptomatic patients.
3
We also considered the influence of the hyperkinetic, hypercoagulable state of
pregnancy on the occurrence of expected complications (thrombosis, myocardial
infarction and sudden death) in this patient. The potential risk of arterial rupture
and/or dissection is increased with presumed arterial changes including
fragmentation of reticular fibers, decrease in mucopolysaccharide content and loss
of normal elastic fiber structure.
4
In the study by Wei et al.,
5
that
included 38 cases of KD, thrombosis was seen in 17 patients, which has been
hypothesized to be caused by insufficient anticoagulant therapy. In a meta-analysis
including 159 children with giant CAA, Su et al.
6
reported that coronary occlusion, AMI and death were
significantly lower in children treated with warfarin plus aspirin than in those
treated with aspirin alone. In this line of thought, the progressive activation of
coagulation factors in the second half of pregnancy, and the maximum activation at
delivery made the authors recommend anticoagulation with dose adjustment combined
with ASA. Enoxaparin was used in place of warfarin during pregnancy due to risk of
hemorrhage and fetal toxicity, in prophylactic dose until week 34 and then
therapeutic dose until 12 hours before delivery. The drug was then restarted until
warfarin was reintroduced for maintenance of INR within target range.
The history of myocardial infarction increased the pregnancy risk, although
ventricular function was preserved and was favorable to patient’s progression.
Increased myocardial metabolic demand, due to increased cardiac output and oxygen
consumption related to pregnancy, was the cause of frequent complaints of angina and
dyspnea, which were controlled by propranolol. At 60 mg/day, the drug did not affect
fetal growth until week 32 of pregnancy. Arterial hypotension, resulting from a
decrease in peripheral vascular resistance, limited the use of nitrates for the
supposed risk of decreased uteroplacental blood flow.
During the third trimester of pregnancy, high-amplitude uterine contractions (Braxton
Hicks) become more frequent and may be confused with premature labor, accounting for
75% of births before week 37 of pregnancy.
7
These contractions cause oscillations in venous return and
in heart rate, and may cause instability in women with limited cardiac reserve,
which was the cause of hospitalization of the patient in the week 32. Together with
the obstetrician, a decision was made to not anticipate delivery, adjust medication
for control of clinical obstetric symptoms until fetal maturity was reached.
With respect to the type of delivery chosen, a study on 13 women with KD
8
and coronary artery lesions, showed
that vaginal deliveries under epidural anaesthesia in 9 patients, and caesarean
section was performed in 3 symptomatic patients. These data corroborate the clinical
decisions made in this case. Also, tubal ligation was chosen as the safest
contraceptive method due to contraindications of a new pregnancy.
Conclusion
This report added to the literature one case of successful term pregnancy in a
symptomatic patient with multiple CAAs secondary to KD and history of myocardial
infarction. The study illustrated the importance of the multidisciplinary approach
to reach the full-term of a high-risk pregnancy. However, family planning, including
counseling on genetics and possibility of a new pregnancy, is still essential. The
risk of complications cannot be neglected regardless of the therapeutic strategy
adopted.