Version May 2024
INTRODUCTION — Myocardial infarction (MI) is an uncommon event in women of childbearing age. However, as the birth rate for women older than 40 years has increased in recent years in some countries such as the United States, MI in pregnant women may become more common [1].
Issues related to acute MI in pregnancy will be reviewed here. Other types of acquired heart disease in pregnancy, such as valvular disease and heart failure, are discussed separately. (See "Acquired heart disease and pregnancy" and "Management of heart failure during pregnancy".)
EPIDEMIOLOGY
●Incidence – In a study analyzing the California State Inpatient Database from 2003 to 2011, the incidence of MI in pregnancy was 6.5 per 100,000 pregnancies (341 cases) [2]. A study from the Nationwide Inpatient Sample of pregnancy discharges between 2000 and 2002 in about 1000 hospitals in the United States showed the incidence was 6.2 in 100,000 pregnancies [3]. It was estimated the risk of MI was increased three- to fourfold compared with nonpregnant women. In a French registry of 6.25 million deliveries, 225 women had a first-time MI; the incidence of MI in pregnancy was 4.34/100,000 person-years [4].
Possible explanations for the increased rate of MI compared with the study above include regional differences and improved detection due to widespread use of troponin testing. (See "Troponin testing: Clinical use".)
●Timing during pregnancy – In a study using data from the National Inpatient Sample from 2002 to 2014 [5], acute MI occurred in 1 of every 12,400 hospitalizations during pregnancy and postpartum with 20.6 percent occurring antepartum, 23.7 percent during the labor and delivery, and 53.4 percent in the postpartum period.
●Temporal trends – MI in pregnancy may be increasing over time since an earlier study from California of births between 1991 and 2000 showed a lower incidence of 2.8 per 100,000 deliveries [6]. Similarly, a separate national United States study showed that the prevalence of MI in pregnancy did increase over these time periods, even after accounting for age and race/ethnicity [5].
RISK FACTORS — Many risk factors for acute MI in pregnant women are similar to those in the general population [2,3,6-9]:
●Older age (age >35 years)
●Black race
●Lower socioeconomic status
●Hypertension
●Diabetes mellitus
●Obesity
●Smoking
●Dyslipidemia
●Substance use (cocaine, amphetamine)
●Treatment for infertility (this is a risk factor for MI due to spontaneous coronary artery dissection) [10].
Risk factors for MI in pregnancy (859 cases) were evaluated in the Nationwide Inpatient Sample [3]. Hypertension (odds ratio [OR] 21.7 95% 6.8-69.1), smoking (OR 8.4, 95% CI 5.4-12.9), and diabetes (OR 3.6, 95% CI 1.5-8.3) were associated with an elevated risk of MI. Maternal age categories of 30 to 35, 35 to 39, and >40 years were each associated with increased risk of MI in pregnancy compared with maternal age <20 years (ORs 6.7, 16, and 15.2). Other maternal risk factors shown to be associated with elevated risk of MI in pregnancy were history of thrombophilia (OR 25.6) and pregnancy complications such as blood transfusion (OR 5.1) and postpartum infection (OR 3.2) [3].
It is not clear if pregnancy itself is a risk factor for MI. In a report with 3.6 million woman-years of observation, the incidence of a first-ever MI not related to pregnancy was 5 per 100,000 woman-years in women of child-bearing age, with the risk increasing dramatically after age 35 [11]. Since pregnancy lasts three-quarters of a year, this rate of MI is not different from the rates in the two large epidemiologic studies cited above (2.8 to 6.2 per 100,000 pregnancies) [3,6].
Other risk factors that have been identified include preeclampsia, thrombophilia, transfusion, postpartum infections, cocaine use, and multiparity [3,6].
ETIOLOGY — Two studies of over 100 pregnant women have evaluated the causes of myocardial infarction using findings at the time of coronary angiography or autopsy and found atherosclerosis to be the direct cause less often than in the general population (see "Mechanisms of acute coronary syndromes related to atherosclerosis"):
●In a review of 103 cases (1995 to 2005), coronary atherosclerosis (with or without) intracoronary thrombus was present in only 40 percent [12]. The remaining cases consisted of coronary artery dissection (27 percent), thrombus in a normal coronary artery (8 percent), coronary artery spasm (2 percent), emboli (2 percent), and normal coronary arteries (13 percent). Most cases occur in the anterior wall [9].
●In a study of 129 cases (2006 to 2011), coronary atherosclerosis was found in 27 percent [9]. The remaining cases included coronary dissection (43 percent), thrombus in a normal coronary artery (17 percent), coronary artery spasm (2 percent), and normal coronary anatomy (11 percent). Three patients were ultimately diagnosed with takotsubo cardiomyopathy.
These two studies found a relatively high incidence of coronary artery dissection. (See "Clinical features and diagnosis of coronary heart disease in women", section on 'Role of coronary angiography'.)
It has been suggested that arterial dissection during or early after pregnancy is related to structural changes in the intima and media of the arterial wall that are produced by hormonal and hemodynamic changes [11,13]. Although dissection can occur in the absence of risk factors, it may occur more frequently in conditions associated with hypertension that independently damage the arterial wall.
In one study, 15 percent of all acute MIs were from coronary artery dissection (note that all patients did not have coronary angiography) [5]. (See "Spontaneous coronary artery dissection".)
In a report of 120 cases of pregnancy-associated spontaneous coronary artery dissections, 72 percent had left anterior descending coronary artery involvement, 36 percent had left main coronary artery involvement, and 40 percent had multivessel involvement. Maternal complications included cardiogenic shock (24 percent), requirement for mechanical support (28 percent), and need for urgent coronary artery bypass graft surgery (27.5 percent). The maternal mortality was 4 percent, and the fatal mortality was 2.5 percent [14].
The American Heart Association has published a scientific statement on spontaneous coronary artery dissection, providing guidelines for management [10].
CLINICAL PRESENTATION — In many cases, pregnant women with acute myocardial infarction (MI) present with symptoms and signs similar to the general population. In brief, patients often complain of the development (over the course of minutes) of chest discomfort that is felt in the anterior chest or epigastric area and often with radiation to the shoulders, arms, jaws, or back. Shortness of breath and nausea may also be present. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Clinical presentation'.)
However, there is some evidence that women more often present with atypical features such as dyspnea or nausea without chest discomfort, palpitations, syncope, or cardiac arrest. (See "Coronary artery disease and myocardial infarction in young people", section on 'Clinical manifestations' and "Clinical features and diagnosis of coronary heart disease in women", section on 'Symptoms of ischemia'.) It is not known whether pregnancy influences the clinical characteristics of the presentation of MI.
A 2014 study of 134 cases identified by literature search and 16 unpublished cases made the following observations [9]:
●Approximately three-quarters of women presented with ST-elevation MI (STEMI) and one-quarter with non-ST elevation MI (NSTEMI).
●For both STEMI and NSTEMI, about half of the cases occurred after delivery; for the remainder, the frequency increased with each trimester.
●The MI was anterior in location in 69 percent, inferior in 27 percent, and lateral in 4 percent
In one study, 42.4 percent of the cases were ST-elevation MIs and 57.6 percent of the cases were non-ST elevation MIs [5].
For patients with coronary artery dissection, takotsubo cardiomyopathy, or coronary artery spasm (see 'Etiology' above), which are uncommon causes of acute MI in the general population, the clinical presentation will differ somewhat from the classic presentation of acute MI secondary to atherothrombotic disease. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy", section on 'Clinical manifestations' and "Vasospastic angina", section on 'Clinical presentation' and "Clinical features and diagnosis of coronary heart disease in women", section on 'Role of coronary angiography'.)
DIAGNOSIS — The diagnosis of acute myocardial infarction (MI) associated with pregnancy is guided by the same principles as in the general population, including ischemic symptoms (eg, anginal chest pain), electrocardiographic (ECG) abnormalities, and elevations in cardiac biomarkers [15]. In terms of cardiac biomarkers, troponins are preferred to creatine kinase MB fraction [16]. (See "Diagnosis of acute myocardial infarction".)
Specifically, acute MI is present when there is a rise and/or fall of cardiac troponin and the presence of one of the following: ischemic symptoms; new Q waves, significant ST-segment-T wave changes, or new left bundle branch block on the ECG; or intracoronary thrombus on angiography.
DIFFERENTIAL DIAGNOSIS — Similar to the general population, another diagnosis may be present in a pregnant woman who presents with symptoms and signs of acute myocardial infarction. Acute pulmonary embolism, aortic dissection, musculoskeletal pain, and gastroesophageal reflux disease should be considered.
●(See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults".)
●(See "Clinical features and diagnosis of acute aortic dissection", section on 'High-risk conditions'.)
●(See "Maternal adaptations to pregnancy: Musculoskeletal changes and pain", section on 'Chest wall pain'.)
The HELLP syndrome, preeclampsia, and acute fatty liver of pregnancy commonly present with severe epigastric pain. (See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)", section on 'Patient presentation' and "Preeclampsia: Clinical features and diagnosis" and "Acute fatty liver of pregnancy".)
MANAGEMENT — In general, the management of acute MI in pregnant women is similar to that in the general population. However, there are also unique considerations in pregnant women with acute MI given that many of the appropriate diagnostic and therapeutic interventions may pose a risk to the fetus.
General strategy and principles — Due to the potential risks of myocardial infarction and its treatment, care should be individualized and involve the highly coordinated efforts of emergency, obstetric/maternal fetal medicine, and cardiovascular healthcare teams. For patients managed in an emergency department setting, immediate consultation of the last two should be requested.
In general, the management of acute myocardial infarction (MI) in pregnant women is similar to that in the general population, including the use of revascularization with percutaneous coronary intervention and stenting or coronary artery bypass graft surgery in patients with fixed coronary artery stenoses [3,15,17-20] (see "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes"). However, as mentioned above, less than fifty percent of cases are attributable to atherosclerotic lesions. (See 'Etiology' above.)
The therapeutic strategy will depend on the etiology of the MI and the stage of pregnancy in which it occurs. For women with a coronary dissection, conservative therapy is recommended, although the optimal management is uncertain. (See "Spontaneous coronary artery dissection".)
In some cases, the mechanism will appear to be primarily thrombus obstruction. Thrombus aspiration and balloon angioplasty should be performed and stenting reserved as bailout.
For pregnant women with MI thought secondary to atherosclerotic obstruction, the optimal use of stents and antiplatelet therapy has not been well studied. The following is our approach in those undergoing stenting:
●Most of our experts choose current (newer) generation drug-eluting stents rather than bare metal stents, although their safety in neonates is not known.
●We treat with at least one month of dual antiplatelet therapy with aspirin and clopidogrel (see "Percutaneous coronary intervention with intracoronary stents: Overview"). A longer duration of clopidogrel (up to three months) may be reasonable in patients at high risk of recurrent ischemia and reasonable bleeding risk. If delivery occurs within that time frame, the obstetrical and anesthesia team should be aware of and prepared to treat an increased bleeding risk. Aspirin is continued indefinitely.
●Heparin is not a substitute for dual antiplatelet therapy as it has not been shown to prevent stent thrombosis.
For some women who have moved beyond the acute phase of an MI, optimal care may include a decision to postpone delivery, perhaps up to two to three weeks after an acute MI [21]. However, there are no clinical trials that have prospectively evaluated the optimal timing of surgical procedures or labor and delivery after an acute (one to seven days) or recent (7 to 30 days) MI, especially in the current era of cardiac therapies and modern anesthesia.
Measures should be taken to minimize the cardiac workload at the time of delivery. These include epidural anesthesia, supplemental oxygen, left lateral position, treatment of hypertension and tachycardia, and either an instrumental vaginal delivery or cesarean birth (in unstable cases or for the usual obstetric indications) [8]. The goal heart rate and blood pressure in patients with acute MI is discussed separately. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Heart rate goal' and "Goal blood pressure in adults with hypertension".)
General issues related to labor and delivery in women with underlying heart disease are discussed separately. (See "Acquired heart disease and pregnancy", section on 'Management of labor and delivery'.)
Protecting the fetus — The fetus should be closely monitored by standard obstetrical protocols with a plan for delivery if there is sudden maternal or fetal deterioration. In the event of maternal cardiac arrest, the best prognosis for the fetus occurs when delivery is within four to five minutes. Delivery may also aid maternal resuscitative efforts. (See "Sudden cardiac arrest and death in pregnancy".)
There are also unique considerations in pregnant women with acute MI given that many of the appropriate diagnostic and therapeutic interventions may pose a risk to the fetus.
Radiation — Ionizing radiation is needed for catheter-based diagnosis and treatment of acute MI. The risk of radiation to the fetus should be taken into account. However, concern about the possible effects of ionizing radiation should not prevent medically indicated diagnostic procedures using the best available modality for the clinical situation. When procedures requiring ionizing radiation are necessary, various techniques can be employed to minimize the radiation dose. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Summary and recommendations'.)
Medications — A study provides a comprehensive review of medications for cardiovascular disease during pregnancy [22]. We provide a more abbreviated review of commonly used and/or considered medications for acute MI during pregnancy.
The following medications appear to be generally safe in pregnancy:
●Aspirin – Low-dose aspirin (75 to 162 mg/day) appears to be safe in pregnancy when given after the first trimester [23,24].
●Nitrates – Intravenous, transdermal, and oral nitrates have been used during pregnancy for both obstetric and medical indications without apparent harmful effects, although maternal hypotension should be avoided [25]. (See "Nitrates in the management of acute coronary syndrome" and "Nitrates in the management of chronic coronary syndrome".)
●Beta blockers – Beta blockers are generally safe for pregnant women. A study using the Kaiser database showed that beta blocker use in pregnancy was not associated with an increased risk of fatal congenital cardiac anomalies [26]. However, occasional cases of small-for-gestational-age infants and neonatal hypoglycemia, respiratory depression, and bradycardia have been reported after prolonged maternal administration of beta blockers, particularly with atenolol [27,28]. Labetalol may be the preferred beta blocker. (See "Treatment of hypertension in pregnant and postpartum patients".)
The safety of the following medications during pregnancy is less well established:
●P2Y12 receptor blocker – All patients with recent acute coronary syndrome are treated with a platelet P2Y12 receptor blocker (clopidogrel, prasugrel, or ticagrelor). The safety of these agents in pregnancy has not been established.
In addition, the combination of a P2Y12 receptor blocker and aspirin might increase bleeding at the time of delivery.
For patients receiving clopidogrel, we and others recommend holding clopidogrel for seven days before a scheduled delivery [29].
A systematic review of antiplatelet therapy in pregnancy examined outcomes for both mothers and neonates when exposed to clopidogrel at varying durations during gestation and did not suggest higher-than-acceptable risk [30].
●Anticoagulation – Heparin does not cross the placenta and thus does not affect the fetus directly. For women who are anticoagulated with heparin for days, weeks, or even months, pregnancy complications associated with bleeding (eg, threatened miscarriage, placenta previa, abruptio placenta) and delivery are more problematic. In such patients, antepartum heparin may have to be discontinued until the bleeding has resolved. In addition, heparin should be discontinued before or during labor to minimize maternal bleeding complications and allow neuraxial anesthesia. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Labor and delivery'.)
However, with the short-term use of heparin, particularly when used during percutaneous coronary intervention for the treatment of acute MI, its benefit likely outweighs the risk of maternal bleeding complications. For the rare cases of a pregnant woman with a history of heparin-induced thrombocytopenia (HIT) who presents with acute MI, the optimal anticoagulant strategy is not known. While bivalirudin is often preferred to fondaparinux in non-pregnant individuals with HIT who sustain acute MI, these agents are generally avoided during pregnancy. Our contributors have differing approaches to the choice of anticoagulant in pregnant women with HIT, with some preferring fondaparinux and some bivalirudin. A review of the use of factor Xa inhibitors is available [29]. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Already taking a DOAC' and "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Summary and recommendations' and "Anticoagulant therapy in non-ST elevation acute coronary syndromes", section on 'Summary and recommendations' and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".)
These medications are contraindicated in pregnancy:
●Statins – Statins are also contraindicated because of lack of information on safety and because cholesterol biosynthesis may be important in fetal development. However, recommendations may change in the future for the use of statins [31].
●Angiotensin converting enzyme (ACE) inhibitors and statins – ACE inhibitors and angiotensin II receptor blockers are teratogenic and thus contraindicated in pregnancy [32]. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy" and "Statins: Actions, side effects, and administration", section on 'Risks in pregnancy and breastfeeding'.)
●Vasoactive drugs – Drugs that can cause coronary vasoconstriction such as methergine and prostaglandin should be avoided.
●Fibrinolytic therapy – There are no controlled studies examining the efficacy and safety of fibrinolytic therapy for acute ST-elevation MI in pregnancy [33,34]. Its use is considered relatively contraindicated. Although teratogenicity has not been reported, the reported risk of maternal hemorrhage is about 8 percent [35]. The risk of puerperal hemorrhage appears to be confined to women treated within eight hours of delivery, although some women have been safely treated, most with disorders other than acute MI [34,36-38]. The risk of bleeding may also be higher after cesarean than vaginal delivery. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)
COMPLICATIONS — In a study of over 100 cases of MI in pregnant women, the rates of complications were as follows [9]:
●Heart failure or cardiogenic shock in 38 percent
●Ventricular arrhythmias in 12 percent
●Recurrent angina or MI in 20 percent
●Left ventricular ejection fraction ≤40 percent in 64 percent, ≤30 percent in 24 percent, and ≤20 percent in 9 percent.
PROGNOSIS — The in-hospital maternal mortality from MI was between 4.5 and 7 percent in published studies [3,5,6,9]. In a study of women with MI in pregnancy from the California State Inpatient Database from 2003 to 2011, inpatient maternal mortality was 7 percent, and the infant mortality rate was 3.5 percent [2]. A study from the National Inpatient Sample from 2002 to 2014 showed that the maternal mortality rate for MI was 4.5 percent [5].
The highest risk for maternal death exists when MI occurs in the late third trimester [6,8]. During labor, further cardiac ischemia and decompensation can develop because cardiac demands are maximal at a time when myocardial healing is incomplete. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes", section on 'Intrapartum changes'.)
REMOTE MYOCARDIAL INFARCTION — There is little information available regarding the risk of subsequent pregnancy in women with a prior history of MI [8,39-41]. People who have received mantle radiation years before their pregnancy may have underlying coronary artery disease that could manifest during pregnancy. About 10 percent of patients will develop significant coronary artery disease, including ostial coronary disease [42]. Counseling women with underlying coronary artery disease is based upon a thorough evaluation of their cardiac status, particularly left ventricular function, ongoing myocardial ischemia, and underlying coronary anatomy. Pre-pregnancy stress testing for women with known coronary disease or women who might be at high risk (prior radiation, etc) is recommended. Changes in the patient's chronic medical regimen would include cessation of angiotensin converting enzyme inhibitors and statins, which are currently contraindicated in pregnancy.
In a study examining the outcome of pregnancies in women with pre-existing coronary artery disease or acute coronary syndromes (ACS), there were relatively high rates of cardiovascular events during pregnancy (10 percent had an arrhythmia, ACS/MI, heart failure, or angina) as well as a high risk of adverse obstetric (16 percent) and fetal/neonatal complications (30 percent) [43].
RECOMMENDATIONS OF OTHERS — We agree with the following specific recommendations made in the 2018 European Society of Cardiology guideline for the management of cardiovascular diseases during pregnancy [44] and American Heart Association Scientific Statement on Cardiovascular Considerations in Caring for Pregnant patients [45]:
●An ECG and troponin level(s) should be performed in pregnant women with chest pain. If the ECG is nondiagnostic, an echocardiogram may be helpful. (See "Diagnosis of acute myocardial infarction" and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
We believe this is a reasonable approach when the managing physicians have a concern that the chest pain is potentially ischemic in origin. Many pregnant women have symptoms of chest pain, but gastroesophageal reflux disease is often the cause.
●Primary percutaneous coronary intervention is recommended as the preferred reperfusion therapy for STEMI in pregnancy. (See "Primary percutaneous coronary intervention in acute ST-elevation myocardial infarction: Periprocedural management".)
●Conservative management should be considered for stable non-ST-elevation ACS with low-risk criteria during pregnancy. (See "Risk stratification after non-ST elevation acute coronary syndrome".)
●Angiography is the gold standard for the diagnosis of ischemic heart disease in pregnancy. Fetal radiation protection and radiation reduction measures should be implemented.
●An invasive approach is recommended for patients with STEMI and for patients with NSTEMI who are unstable or have a high atherosclerotic burden. Stable patients at low risk can be managed conservatively.
●Conservative management is recommended for those found to have pregnancy-related spontaneous coronary artery dissection.
●Antiplatelet agents (low-dose aspirin and clopidogrel) combined with beta blockers represent the most accepted regimen.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of cardiovascular diseases during pregnancy".)
SUMMARY AND RECOMMENDATIONS
●Diagnosis – The diagnosis and management of acute myocardial infarction (MI) in pregnant women is guided by the same principles as in the general population. (See 'Diagnosis' above.)
●Team-based care – In order to negotiate the potential conflicting needs of the mother and fetus, care should be highly coordinated among the emergency, obstetric, and cardiovascular teams.
●Close fetal monitoring – The fetus should be closely monitored. There should be a plan for delivery if there is sudden maternal or fetal deterioration.
●Management – The management of acute MI in pregnant women is guided by the same general principles as in the general population. However, some medications used during MI in the general population should be used with extra caution or are contraindicated during pregnancy. (See 'Management' above.)
•Low-dose aspirin (75 to 162 mg/day), beta blockers, and nitrates have been used during pregnancy without apparent harmful effects.
•Cardiac catheterization and possible percutaneous coronary intervention are recommended for high-risk patients (ST-elevation MI). Fibrinolytic therapy is relatively contraindicated. When procedures requiring ionizing radiation are necessary, various techniques can be employed to minimize the radiation dose. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Summary and recommendations'.)
•Heparin does not cross the placenta and thus does not affect the fetus directly. However, pregnancy complications associated with bleeding (eg, threatened miscarriage, placenta previa, abruptio placenta) are more problematic in a person who is anticoagulated.
●Medications that are contraindicated or should be avoided – Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and statins are contraindicated in pregnancy. Drugs that can cause coronary vasoconstriction such as methergine and prostaglandin should be avoided after myocardial infarction.
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