1. An acute myocardial infarction during pregnancy can be missed because it is mistaken for a variety of more common causes of chest pain, such as acid reflux and musculoskeletal disorders. The diagnosis should therefore be considered, and investigated appropriately, in any woman presenting with chest pain in pregnancy.
6. All pregnant women with angina or myocardial infarction should be treated by a multidisciplinary team in a tertiary center.
The prevalence of coronary artery disease in women is increasing owing to changing patterns of lifestyle, including cigarette smoking, diabetes, overweight, and stress. In 1989, it was reported that approximately 10% of women with myocardial infarction were under the age of 40 years. Since then, women have increasingly been having their first pregnancy at a later age, and a higher incidence of acute myocardial infarction during pregnancy is therefore to be expected in the future. When infarction occurs in pregnancy, it constitutes a particular problem because the selection of diagnostic and therapeutic approaches is greatly influenced not only by maternal but also by fetal considerations. The risk of a myocardial infarction in women during pregnancy was estimated in 2006 as 6.2 per 100 000 deliveries, which is 3–4 times higher than in young women outside pregnancy. Myocardial infarction can occur at all stages of pregnancy, but there is a clear peak of incidence in the third trimester. The majority of pregnant women suffering from myocardial infarction are older than 30 years.[3,4] Other risk factors for pregnancy-associated myocardial infarction are thrombophilia, hypertension, smoking, transfusion, diabetes, and postpartum infection.
In normal pregnancy, circulatory changes not only ensure the adequate supply of nutrients and oxygen to the developing fetus but also change the load on the cardiac muscle. Blood volume and cardiac output increase by 40–45%. This increase peaks at around the 24–26th weeks of gestation and stays high or slowly decreases thereafter until term. Furthermore, there is an increase in heart rate of 20–25 beats/min throughout the entire pregnancy. Gestational hormones and circulating prostaglandins, in combination with the low vascular resistance of the placenta and the uterus, decrease both the peripheral vascular resistance and blood pressure. During labor, the uterine contractions result in a further increase in cardiac output. Finally, after delivery, there is a significant increase in cardiac preload as a result of decompression of the inferior vena cava and the return of uterine and placental blood into the circulation. Reabsorption of extracellular fluids into the circulation in the postpartum period results in an increase in intravascular volume. Most hemodynamic adaptations resolve within 2–6 weeks postpartum.
During pregnancy there is a higher risk of thrombotic events owing to hypercoagulability induced by hormone changes. The changed cardiac and hemodynamic situation, especially the hypercoagulability during pregnancy and the postpartum period, contribute to the spectrum of causes of myocardial infarction. In addition, it has been suggested that the increase in progesterone level plays a part in the etiology. Progesterone influences the collagen within the vessel wall, thus enhancing the risk of coronary dissection. In a review of women who underwent coronary angiography during pregnancy, coronary dissection was found in 43%, atherosclerosis in 27%, and a thrombus without signs of atherosclerosis in 17%. Coronary dissection was the primary cause of infarction in the postpartum period, but also occurred in the third trimester. Normal coronary arteries were reported in 11% of the women, while coronary spasm was observed in only 2 of the 129 patients.
The estimated mortality in pregnancy during acute myocardial infarction before the current practice of percutaneous coronary intervention (PCI) was 20–37% for the mother and 17% for the baby.[7,8] A 2011 study reported that the population-based mortality rate due to myocardial infarction was 0.47 per 100 000 maternities, which agrees with the maternal mortality rate of 7% of women who actually suffer from myocardial infarction during pregnancy. The diagnosis is often missed because chest pain can occur during normal pregnancy, for instance caused by reflux, and also because the physician does not expect a myocardial infarction to happen at this young age because of the relatively low incidence. The differential diagnosis of ischemic chest pain includes gastric problems, hemorrhage, preeclampsia, acute pulmonary embolism, and aortic dissection. The diagnosis is confirmed by the characteristic electrocardiographic changes, an increase in the cardiac enzyme troponin, and echocardiographic evidence of local myocardial dysfunction.
In the acute phase, the treatment options for an acute myocardial infarction are PCI, thrombolysis, or coronary artery bypass grafting. At present, the primary choice of treatment in the general population is PCI with stenting, which should also be the first choice in pregnant women. However, the selection of diagnostic and therapeutic approaches during pregnancy is influenced by considerations of both maternal and fetal safety.
Treatment of acute coronary syndrome in pregnancy is not based on randomized trials but instead on limited data from case reports (success tends to be over-reported compared with failure), observational studies, registries, and individual clinical experience. During cardiac catheterization, <20% of the radiation exposure reaches the fetus because of tissue attenuation. Radiation exposure to the fetus is kept to a minimum if PCI is performed through the radial artery. Furthermore, shielding the gravid uterus from direct radiation, shortening of fluoroscopic time, and delaying the procedure until at least the completion of the period of major organogenesis (up to 15 weeks after the last menstrual period) will all minimize potentially teratogenic radiation exposure. The amount of fetal exposure will be around 0.02 mSv, with a maximum of 0.1 mSv in difficult PCI procedures (Table 17.1). Fetal risks are considered negligible if fetal exposure is <50 mSv. Therefore, PCI should probably be considered acceptably safe but should still only be used during pregnancy when absolutely necessary because of possible detrimental effects on the fetus (Table 17.2). The 8th to 15th week of gestation is the most radiation-sensitive period as far as the fetus is concerned.
Fetal dose (mSv)
CT = computed tomography; PTCA = percutaneous transluminal coronary angioplasty
|Period of exposure||Effect||Incidence (%)||Comments|
|Up to 8 days||Spontaneous abortion||50–75||Rejection, all or nothing|
|9 days to 8 weeks||Deformation of organs||6||Small change—a relatively high dose is needed|
|8–15 weeks||Mental retardation||0.5||500–1000 mSv: brain damage, from lower IQ to severe incomplete development 500 mSv: delayed growth, mental retardation (3 IQ points per 100 mSv)|
|After 15 weeks||Childhood cancer||0.1||–|
IQ = intelligence quotient
Equally, as with PCI, there is little experience with thrombolytic therapy for myocardial infarction during pregnancy. Streptokinase and low-dose recombinant tissue plasminogen activator (rtPA or alteplase) do not cross the placenta in animals. There is very little information available regarding humans, but the placental transfer of both streptokinase and rtPA seems to be insignificant. Most experience with thrombolytic therapy during pregnancy had been with streptokinase in women with pulmonary embolism, deep venous thrombosis, or cardiac valve thrombosis. Complications that have been reported include maternal hemorrhage, uterine hemorrhage at emergency cesarean section, preterm delivery, fetal loss, fatal placental abruption, postpartum hemorrhage, and spontaneous miscarriage. Hemorrhagic risks increase if thrombolytic therapy is given at the time of delivery. Therefore, PCI is the first choice therapy during pregnancy, not only because of the relatively low fetal risks but also because thrombolysis may be harmful in cases of a coronary dissection. The use of stenting during PCI implies the use of platelet aggregation inhibitors in the post-PCI period, regardless of the type of stent. No information is available on the effects of clopidogrel and prasugrel on the fetus, although animal experiments have not shown a teratogenic effect and, so far, experience in humans is reassuring. The alternative in general practice, ticagrelor, has shown adverse effects in animal studies and is contraindicated. Therefore, in these women balloon dilatation without stenting may be considered, although stenting with the use of clopidogrel seems to be the best option. The majority of experience with coronary stenting during pregnancy consists of treatment with a bare metal stent. Little is known about the use of a drug-eluting stent in pregnancy, probably due to the fact that it necessitates an extended use of antiplatelet therapy.
Because of the hypercoagulable state of pregnant women, thrombus formation can be a cause of myocardial infarction. Treatment with low-molecular-weight heparin is generally safe during pregnancy. More recently, IIb/IIIa-receptor inhibitors have been introduced. However, there are no clinical or experimental data available on the fetal effects of this drug; therefore, they are not currently recommended for use during pregnancy. Morphine, which is used to treat the pain of myocardial infarction, does not cause teratogenic anomalies but crosses the placenta and can cause respiratory depression if given shortly before delivery. Specific information on the safety of nitrates and sodium nitroprusside is lacking. Intravenous as well as oral nitrates have been used in women for the treatment of hypertension, myocardial ischemia, and heart failure, and seem safe. However, case reports of fetal heart decelerations associated with their use have been reported (most likely from decreased placental perfusion associated with hypotension).[17,18]
After the acute phase of myocardial infarction, several drugs can be used to reduce the risk of recurrence or reduce the progression of atherosclerosis. In general, beta-blockers are relatively safe during pregnancy, although a negative effect on birthweight can be expected. The calcium antagonist diltiazem should be avoided because of its suggested teratogenic effect. Aspirin in low doses (<150 mg/day) is considered safe. High doses can cause premature closure of the arterial duct, fetal congenital abnormalities, and fetal and maternal hemorrhage.[20–23] Angiotensin-converting enzyme (ACE) inhibitors are contraindicated during pregnancy because of their fetotoxic effects. Reported complications include fetal and neonatal renal failure, oligohydramnios, fetal growth restriction, and hypoplasia of the skull bones (especially in the second and third trimester).
There are no data available on the use of angiotensin II receptor antagonists in pregnancy, but their actions are similar to those of ACE inhibitors and so most clinicians consider them to be contraindicated. Treatment options in myocardial infarction with cardiac failure are diuretics (furosemide) and hydralazine, which are considered safe. Spironolactone and thiazides are not recommended because of reports of adverse fetal effects.[26–28] Statins are not advised because some reports of fetotoxic effects have been published. However, in high-risk women continuation of statins may be considered because fetal abnormalities seem not to be very common.