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Acute Coronary Syndromes in Pregnancy

Pavan Reddy, Gassan Moady, and Uri Elkayam

Introduction

The term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with acute myocardial ischemia and includes unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). Pregnancy-associated myocardial infarction (PAMI) is defined as myocardial infarction (MI) occurring during pregnancy or within 6–12 weeks postpartum [1].

Incidence

Recent systemic review and meta-analysis of population-based studies including over 66 million pregnancies reported a pooled PAMI incidence of 1:30,000 worldwide and the U.S. incidence of 1:20,500 [2]. When compared to nonpregnant women in similar age, the incidence in pregnancy is three- to fourfold higher [2–6].

Etiology of Acute Coronary Syndromes in Pregnancy

In a large series published in 2014 by Elkayam et al., the main mechanisms of PAMI were spontaneous coronary artery dissection (SCAD), accounting for 43% of cases, atherosclerotic plaques in 27%, coronary artery thrombosis without atherosclerosis in 17%, normal coronary arteries in 9%, Takotsubo cardiomyopathy in 2%, and suspected coronary spasm in 1% of the cases [7]. Increased incidence of SCAD in this group of women is likely due to the increased estrogen and progesterone levels in pregnant women, which tends to accelerate degenerative changes in the vessel wall with the potential for coronary artery dissection [8,9]. The left anterior descending (LAD) artery is the most involved vessel (more than 70%), followed by the left main coronary artery, circumflex, and then the right coronary artery. Involvement of multiple coronary vessels in the dissection process is not an uncommon finding in pregnancy [9].

Risk Factors

Older age is a known risk factor, with over 70% of women with PAMI being older than 30 years and 40% over the age of 35 years. For women older than 40 years of age, the risk of ACS during pregnancy increases by 20% with each advancing year [10]. The incidence of conventional atherosclerotic risk factors is relatively low in the young female population, ranging between 10%–25% [7]. Incidence of PAMI has been also reported to be higher in pregnant women with thrombophilia, history of postpartum infections, anemia requiring transfusions, multiparity, non-Hispanic whites, and African Americans [3,4]. Notably, pregnancy and postpartum periods are known hypercoagulable states in part due to alterations in the coagulation cascade [11]. Table 14.1 summarizes the reported risk factors in women with PAMI.

Complications and Mortality

A recent review of 150 contemporary cases reported 7% maternal and 5% fetal mortality [7]. Top causes of maternal mortality were cardiogenic shock and ventricular arrhythmias. The rate of significant complications was strikingly high and included a markedly reduced LVEF (≤40%) in 54% of the patients. This degree of LV dysfunction was associated with a high incidence of heart failure, cardiogenic shock, ventricular arrhythmias, and mortality. Clinical deterioration required mechanical support, including the use of intra-aortic balloon pump, LV assist device, and extracorporeal membrane oxygenation in 28% of the patients with PAMI due to SCAD [9].

Diagnosis of Myocardial Infarction in Pregnancy

Diagnosis of PAMI is made when STEMI or NTSEMI occur during pregnancy or within 6–12 weeks postpartum. The term ACS encompasses a spectrum of pathology pertaining to the degree of coronary occlusion.

•STEMI is defined as ST elevation or left bundle branch block on ECG with evidence of myocardial injury, i.e., troponin elevation. STEMI almost invariably represents complete acute occlusion of a coronary artery with resultant transmural infarct (involving the entire ventricular wall segment).

•NSTEMI is present when there is troponin elevation but without ST elevation on ECG. ST depression or T wave inversion may or not be present and are not required for diagnosis. Pathologically, NSTEMI often represents subtotal occlusion of a coronary artery resulting in less severe injury (subendocardial).

•Unstable angina is characterized by cardiac chest pain without troponin elevation [12]. UA is denoted as such given the propensity to evolve into more severe forms of MI.

•Angina, considered apart from the ACS spectrum of disease, is defined as chest pain that occurs with stress and is relieved with rest or nitroglycerin [13]. Angina specifically pertains to stable ischemic heart disease for which the treatment mainly involves conservative measures such as lifestyle modifications and anti-anginal medications (i.e., beta-blockers or calcium channel blockers).

Most reported PAMI cases occur either late in pregnancy or in the postpartum period, primarily presenting as STEMI involving the anterior ventricular wall [7–9].

As in nonpregnant women, PAMI is diagnosed when the above definitions of STEMI and NSTEMI are met in the right clinical setting. The leading presenting symptoms are chest pain and dyspnea (Table 14.2) [7–9]. Differential diagnosis includes pulmonary embolism, aortic dissection, and preeclampsia.

Cardiac troponin is still the preferred biomarker for evaluation of acute MI. In general, troponin levels are not altered in normal pregnancy. Mild elevations of cardiac troponin levels may be seen in hypertensive women and individuals with preeclampsia [14,15]. Of note, minor electrocardiographic changes involving the ST segment and T wave have been reported in otherwise healthy pregnant women during labor and delivery [16].

Echocardiogram (ECG) is a very useful tool that is safe in the diagnostic workup of pregnant patients with chest pain or suspected MI. Nearly all patients with MI demonstrate wall motion abnormalities.

Exercise stress test, with or without ECG, can be used in pregnancy to diagnose inducible ischemia after ruling out MI and when the patient’s hemodynamic condition is stable. The use of submaximal test (70% of maximal predicted heart rate) is recommended due to previous reports of fetal bradycardia and reduced fetal heart rate variability during maternal moderate to heavy exercise [17].

Computed coronary tomography angiography can be useful for ruling out acute coronary syndrome in questionable cases, but it carries the risk of radiation exposure and has lower sensitivity for lesions in small distal vessels. In addition, for optimal visualization of the coronary tree, high doses of beta-blockers may be needed for lowering heart rate [18].

Management of Myocardial Infarction in Pregnancy

Women with PAMI should be managed in intensive care units. Similar to nonpregnant individuals, coronary angiography with the goal of opening the infarct-related artery is the standard of care in pregnant women with STEMI and in most high-risk patients with NSTEMI.

Medical Therapy

Medical therapy used in MI includes beta-blockers, calcium channel blockers (CCB), nitrates, anticoagulants, statins, and antiplatelet therapy. Beta-blockers should be used when benefits outweigh risks; the use of selective beta-1 agents is preferred due to fewer effects on uterine activity [19,20]. Currently only nifedipine, a dihydropyridine CCB, has been shown to be safe during gestation [21]. Oral and intravenous nitrates have been used during pregnancy for treating hypertension, but careful titration is needed to avoid maternal hypotension [22]. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are contraindicated during pregnancy due to multiple teratogenic effects [23]. Information about the use of statins during pregnancy is limited, however, there are conflicting reports of teratogenicity [24]. The use of statins has been classified as contraindicated in pregnancy [23]. Both heparin and low molecular weight heparin (LMWH) do not cross the placenta and are considered safe in pregnancy [25]. Use of low-dose aspirin is also considered safe for use in pregnant women. Limited information is available regarding the fetal safety of standard antiplatelet drugs, including clopidogrel (category B), prasugrel (category B) and ticagrelor (category C) [26]. Clopidogrel use was reported in 56 patients in two contemporary studies and should be considered the preferred P2Y12 receptor antagonist in pregnancy [7,9]. Although its use decreased substantially in the era of percutaneous coronary intervention, thrombolytic therapy should be considered in pregnant women in appropriate conditions similar to nonpregnant women. However, caution should be exercised given the lack of controlled clinical trials including pregnant women and the nature of the weak evidence level of the cumulative data available [27]. The role of heparin for SCAD is controversial because of the potential risk of extending the dissection with anticoagulation, which on the other hand may be beneficial for resolving overlying thrombus and improving true lumen patency. Thrombolytic therapy should be avoided in SCAD because of the reported harm and clinical deterioration due to extension of intramural hematoma and dissection [28]. Beta-blockers play an important role in the pharmacological armamentarium for SCAD because of their reducing effect on the coronary arterial wall stress.

Coronary Angiography

Coronary angiography in pregnancy is associated with increased risk of catheter-induced coronary artery dissection, especially in the left main artery; this iatrogenic risk together with the documented high rates of spontaneous healing of the dissected arteries leads to the suggestion of conservative management in stable low-risk patients [9,29]. Nonselective contrast injection in the aortic root, avoidance of deep catheter intubation (especially with the radial approach), and minimal use of low-pressure injections are recommended to decrease the risk of dissection. A suggested algorithm for the treatment of PASCAD is given in Figure 14.1. Fetal radiation exposure remains a significant concern during cardiac catheterization of pregnant women, as the average amount of radiation exposure to the fetus is estimated at 3 mSv. External abdominal shielding, lower magnification, low fluoroscopy frame rates, and using the radial approach are acceptable methods to reduce risk of radiation exposure [26].

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