Keywords myocardial infarction - hypertension - pregnancy - multiparity - advanced maternal
age - smoking
Acute myocardial infarction (MI) in pregnancy is a rare event with an incidence of
∼1 in 10,000 to 36,000, and it is associated with significant maternal and fetal morbidity
and mortality.[1 ]
[2 ] The trend toward delayed childbearing is expected to increase the frequency of coronary
artery disease (CAD) and acute coronary syndrome in pregnancy.[3 ] Among women older than 35 years, commonly referred to as advanced maternal age,
there is an increased prevalence of atherosclerotic risk factors, such as diabetes,
hyperlipidemia, hypertension, obesity and metabolic syndrome.[4 ] Women who smoke during pregnancy have an eightfold higher risk of MI.[2 ] Pregnancy itself increases the risk nearly 4-fold with approximately two-thirds
of such cases occurring in multiparous women over the age of 30 years.[5 ]
[6 ] The increased risk during gestation is thought to result from the numerous maternal
physiological changes that occur including hypercoagulability, vascular dysfunction,
and increased myocardial oxygen demand.
Management of MI in pregnancy has been previously discussed in the literature,[3 ]
[5 ]
[7 ] but management of pregnancy following an early antepartum MI, which may have more
consequences for the fetus, has not received as much attention. Here, we present a
case of a first trimester MI in a great grand multiparous female and her subsequent
pregnancy course, which was complicated by poorly controlled chronic hypertension.
This is followed by a discussion of critical issues and challenges in ongoing pregnancy
management after a recent MI.
Case
A 38-year-old great grand multiparous African American woman, body mass index 27 kg/m2 , presented to the emergency department of a community hospital complaining of acute
onset chest pain radiating to the shoulders bilaterally. She denied shortness of breath.
The patient had a 15-year history of poorly controlled chronic hypertension and was
an active smoker of approximately two packs of cigarettes per day. There was no prior
history of cardiac disease, thromboembolic events, or dyslipidemia. There was also
no reported family history of premature CAD. Her obstetric history included 5 term
and 7 preterm deliveries, including one cesarean for breech presentation followed
by 9 subsequent vaginal births. A 12-lead electrocardiogram (EKG) showed transient
ST segment elevation in the inferior leads. She was incidentally found to have a serum
human chorionic gonadotropin of 264 mIU/mL. Transvaginal ultrasound noted a cystic
structure within the uterus suggestive of an early intrauterine pregnancy. On the
basis of her last menstrual period, she was 5 weeks of gestational age.
The patient was transferred to the coronary care unit of a tertiary referral center
with a diagnosis of non-ST elevation MI (NSTEMI). She received aspirin, clopidogrel,
heparin, metoprolol, morphine, and had persistent chest pain that was only relieved
with intravenous nitroglycerin. Serial cardiac muscle enzymes demonstrated a cardiac
troponin T (cTnT) of 0.11, 0.12, and 0.15 ng/mL, and a creatine kinase-MB (CK-MB)
of 3.14, 9.72, and 15.33 ng/mL. Serum cholesterol levels and hemoglobin A1c were normal. Echocardiography noted segmental left ventricular dysfunction with inferior
and inferolateral wall hypokinesis and an ejection fraction of 49%. Urgent cardiac
catheterization and coronary angiography were performed after the patient was counseled
about the risks and benefits, including the potential effects of ionizing radiation
exposure on the developing pregnancy. Stenosis of 80% in the proximal circumflex artery
was noted, along with a small filling defect consistent with a thrombus ([Fig. 1A ]). A successful primary percutaneous coronary intervention (PCI) was performed and
an Integrity 2.5 × 22 mm bare metal stent (BMS) was implanted ([Fig. 1B ]; Medtronic, Minneapolis, MN). Radiation exposure to the embryo was minimized during
the fluoroscopic procedure by utilizing abdominal lead shielding and limiting the
total number of views (Total dose was 106 mGy.). The patient was then started on a
regimen of aspirin (81 mg daily), clopidogrel (75 mg daily for 1 month), and metoprolol
(12.5 mg twice-daily). She was discharged in stable condition on hospital day 3 and
strongly counseled for immediate cessation of smoking.
Fig. 1 Coronary angiography. (A ) Stenosis of proximal circumflex artery with a small filling defect (arrow) consistent
with a thrombus. (B ) Successful percutaneous coronary intervention with bare metal stent placement.
Approximately 3 weeks after the diagnosis and management of acute MI, a transvaginal
ultrasound was performed for pregnancy dating. At that time, a single intrauterine
gestation was noted with a crown-rump length of 1.2 cm, corresponding to an estimated
gestational age of 7 weeks and 3 days, consistent with her last menstrual period.
The patient's subsequent prenatal course was complicated by poorly controlled hypertension
and multiple admissions for hypertensive urgency. She continued to smoke throughout
most of her pregnancy and received inconsistent medical care due to inadequate childcare,
poor transportation, and psychosocial stress. The patient frequently missed scheduled
prenatal and cardiology appointments and admitted to occasional noncompliance with
medications. She was admitted for blood pressure (BP) monitoring and management at
19, 21, 24, and 30 weeks of gestational age. These admissions were sometimes associated
with headaches. During each hospital stay, severe range BPs (>160/110) were documented,
and a 24-hour urine protein collection and laboratory evaluation were performed, consistently
ruling out superimposed preeclampsia. At 24 weeks of gestational age, she admitted
to noncompliance with the metoprolol, which was then discontinued, and she was started
on methyldopa 500 mg twice daily. She also received betamethasone for fetal lung maturity
at this time, due to a history of multiple extremely preterm births (<28 weeks) and
her poorly controlled hypertension that may necessitate early delivery. At 30 weeks,
she was started on labetalol 200 mg twice-daily, in addition to the prior methyldopa
regimen. Aspirin was continued throughout the pregnancy.
Fetal surveillance in the third trimester was consistently reassuring. Biometry demonstrated
appropriate growth. Amniotic fluid volume was normal. Biophysical profiles were 8/8.
Nonstress tests were reactive and category 1.
The patient was again admitted for observation at 36 3/7 weeks of gestation for elevated
BPs. Her systolic BP soon rose above 200 mm Hg, and she developed a headache. Platelet
count, liver enzymes, and creatinine were normal. Urinalysis was negative for protein.
She received multiple pushes of intravenous labetalol. Although the laboratory evaluation
was negative, she was given a diagnosis of superimposed preeclampsia and the decision
was made to induce labor based on BPs that were increasingly resistant to medical
management and a new onset severe headache which was taken as evidence of end-organ
dysfunction. Aspirin was discontinued. A magnesium bolus was administered. Given the
increased propensity for fluid retention with magnesium, levetiracetam 500 mg twice-daily
was started for maintenance seizure prophylaxis. The patient was induced with oxytocin,
received epidural anesthesia during labor, and ultimately had an uncomplicated vaginal
delivery of a female newborn, weighing 2,490 g, with Apgars of 8 and 9 at 1 and 5
minutes, respectively.
The postpartum course was also complicated by severe range BPs requiring intravenous
pushes of labetalol and hydralazine. Oral labetalol was increased to 400 mg three
times daily and methyldopa was increased to 500 mg three times daily. She was discharged
home on this regimen and her aspirin was resumed. The newborn had an uneventful hospital
course. No malformations were observed and early postnatal development was normal.
Discussion
Although cases have been reported in all trimesters, pregnancy-associated acute MI
is more common later in gestation, with three quarters occurring either in the third
trimester or in the puerperium.[6 ]
[8 ] The most common etiology, both during and outside of pregnancy, is atherosclerotic
plaque rupture.[5 ] Other etiologies include thromboembolism, coronary artery spasm and coronary artery
dissection. Heart failure and cardiogenic shock are the most common maternal complications,
present in nearly 40% of patients. Other complications include recurrent angina or
MI (20%), ventricular arrhythmias (12%), and maternal death (5%).[2 ]
[6 ] If an MI is not recognized and not appropriately treated, maternal mortality may
approach 50%.[3 ] Most fetal deaths occur secondary to maternal death. Neonatal complications may
include prematurity and low birth weight, depending on the gestational age at which
the MI occurred.[1 ]
Normal pregnancy is associated with numerous maternal cardiovascular changes which
collectively increase the risk of MI. Myocardial oxygen demand is increased by an
expansion of circulating blood volume and a corresponding increase in cardiac output.
A hypercoagulable state increases the risk of thromboembolism. In addition, labor
and delivery are associated with increased hemodynamic stress. During labor, increased
cardiac output occurs secondary to pain-induced catecholamine secretion, and after
delivery, it occurs due to autotransfusion from the uterus and resorption of edema.[9 ]
Diagnosis of MI in pregnancy may be delayed and patients may receive suboptimal care
because the presenting symptoms are often difficult to distinguish from common pregnancy
ailments such as gastrointestinal reflux, musculoskeletal pain, nausea, vomiting,
dizziness, and physiologic dyspnea. Furthermore, other serious conditions may occur
in pregnancy such as acute pulmonary embolism and aortic dissection, which must also
be ruled out. Therefore, the workup may be insufficiently thorough if ischemic heart
disease is not considered. The diagnostic criteria for MI in pregnancy are essentially
the same as outside of pregnancy, and include ischemic symptoms, EKG abnormalities
and elevations in cardiac biomarkers.[7 ] However, pregnancy may affect biomarker concentrations. Troponins are preferred
over CK-MB, especially during labor and delivery, because uterine contractions and
cell breakdown may increase myoglobin, creatine kinase and CK-MB.[10 ]
Many aspects of medical and interventional management of MI are compatible with pregnancy,
but there are known risks and areas of uncertainty where limited data exists. The
fetal risks associated with ionizing radiation exposure from revascularization procedures
are related to the stage of pregnancy and the absorbed dose. The most sensitive period
is from 8 to 15 weeks of gestation when malformations associated with the central
nervous system may occur at doses above 100–200 mGy.[11 ] Embryonic loss may occur at similar doses during the preimplantation and presomite
stages, but there does not appear to be an increased risk of congenital malformations
or growth restriction in surviving pregnancies.[12 ] Although high doses of radiation (e.g., > 500 mGy) to the embryo or fetus are known
to increase the risk of childhood cancer, the risk associated with exposures less
than 100–200 mGy remains uncertain.[12 ] Some medications used in the treatment of MI, such as, angiotensin-converting enzyme
inhibitors and angiotensin-receptor blockers, are contraindicated in pregnancy owing
to their association with fetal renal and cardiac abnormalities. Statins are also
contraindicated in pregnancy based on a theoretical teratogenic risk demonstrated
in some animal studies.[13 ] Clopidogrel does not appear to be teratogenic based on animal studies and case reports.
Although its safety in human pregnancy also remains uncertain, the benefits of clopidogrel
are thought to outweigh the risks.
Treatment of acute MI in pregnancy should be individualized, given the potential for
conflict between the needs of the mother and the fetus. A multidisciplinary team approach
is recommended. Medical therapy should include antiplatelet agents (both aspirin and
clopidogrel), antithrombotic agents (unfractionated heparin or enoxaparin), and β-blockers.
Pain control can be achieved with nitrates and/or morphine. Although there may be
hesitation to perform interventional procedures in obstetric patients, PCI can be
safely performed. Early revascularization is essential in cases of ST elevation MI
or cases of NSTEMI with recurrent ischemic symptoms or persistent EKG changes.[7 ] The primary advantage of a BMS over a drug-eluting stent in pregnancy is that a
BMS does not require long-term dual antiplatelet therapy, which may increase the risk
of postpartum hemorrhage. The main disadvantage is that it is associated with a higher
rate of in-stent restenosis.[7 ] Systemic thrombolysis with recombinant tissue plasminogen activator (rTPA) may be
performed during pregnancy if the hospital has no PCI capability and reperfusion therapy
is clinically indicated, as long as there are no absolute contraindications. Although
rTPA does not cross the placenta, there is a risk of retroplacental hemorrhage and
placental abruption.[14 ]
There are no established guidelines for the management of pregnancy after an early
antepartum MI. Outside of pregnancy, a persistently elevated systolic BP (>140 mm
Hg) 6 months after an MI is associated with an increased risk of subsequent cardiovascular
events.[15 ] It was previously thought that tight control of maternal hypertension during pregnancy,
using antihypertensive therapy to normalize BP, may be detrimental to the fetus, possibly
contributing to fetal growth restriction. However, Magee et al recently demonstrated
that there is no significant difference in the risk of adverse perinatal outcomes
with tight versus less-tight control.[16 ] Therefore, tight control of BP, which is more beneficial for the mother, may be
more appropriate in pregnancy after a recent MI. In late gestation, one of the primary
concerns is finding an appropriate balance between the risk of bleeding and the risk
of thrombosis. If dual antiplatelet therapy is continued throughout gestation, it
may be discontinued one week prior to a scheduled delivery and low-molecular-weight
heparin can be initiated. However, this may not be as efficacious for the prevention
of stent thrombosis. During labor and delivery, cardiac demands should be minimized.
Vaginal delivery with early epidural anesthesia is preferred in most cases. Operative
assistance with vacuum or forceps should be considered to reduce maternal effort.
Cesarean delivery should be reserved for the usual obstetric indications and for patients
with active myocardial ischemia or poor cardiac function, as defined by a significantly
reduced left ventricular ejection fraction.[8 ]
[17 ] Methylergonovine is associated with vasospasm and should be avoided in the management
of postpartum hemorrhage. Non-steroidal anti-inflammatory drugs may exacerbate hypertension
and should be avoided for postpartum analgesia.
The mother in this case, who had multiple atherosclerotic risk factors, experienced
an NSTEMI in the first trimester of pregnancy requiring PCI and her subsequent prenatal
course was complicated by poorly controlled chronic hypertension. She received a diagnosis
of superimposed preeclampsia with severe features necessitating a medically indicated
late preterm delivery. There was no evidence of fetal growth restriction. It is possible
that the hormonal milieu of early pregnancy, in combination with the patient's underlying
risk factors, precipitated her acute ischemic event. Nonadherence to antihypertensive
therapy may have contributed to her resistant hypertension.
In summary, good pregnancy outcomes are possible after early antepartum MI, especially
with early diagnosis, appropriate treatment, and a multidisciplinary team approach
to prenatal care. Delivery should occur in a tertiary referral center with experience
managing high-risk obstetric patients with cardiac disease.
