Coronary artery vasospasm induced acute myocardial infarction in pregnancy: a new case and systematic review of the literature

Introduction

Acute myocardial infarction (AMI) in pregnancy, although rare, can be a debilitating condition affecting both mother and fetus. The pathogenesis of AMI in pregnant women may be different compared to the general population in that atherosclerotic disease is less common. Other causes such as coronary artery dissection and spasm may be more prevalent. Some hypotheses for increased risk of coronary artery vasospasm (CAV) in pregnancy include enhanced vascular reactivity and renin release from decreased uterine perfusion in the supine position [1]. The subset of AMI in pregnancy due to CAV, when diagnosed in timely fashion, requires targeted therapy in the form of nitrates and calcium channel blockers. Our objective is to present a new case of AMI associated with CAV in pregnancy, and review other similar case reports in the literature.

Case

A 36-year-old gravida four para three African-American woman at 32 weeks of gestation initially presented to an outside hospital with substernal chest tightness radiating to the left neck and jaw, associated with palpitations and sweating. No aggravating or alleviating factors were described. The patient’s past medical history included mild intermittent asthma and sickle cell trait as well as a history of multiple joint repairs including left anterior cruciate ligament and medial collateral ligament repairs, bilateral rotator cuff repairs and pelvic plate placement all in the setting of vigorous exercise as a collegiate basketball player. The patient had no family history of coronary artery disease, connective tissue disease or thrombophilia. There was no history of tobacco, drug or alcohol use. She had three uncomplicated pregnancies with normal vaginal deliveries at term.

At the outside hospital, significant labs included the first and second troponin-I which were elevated to 9.98 and 21.75 ng/mL, respectively. The electrocardiogram (EKG) after symptoms had resolved showed a normal sinus rhythm with occasional premature ventricular complexes and a prolonged QTc of 484 ms without ST segment or T wave abnormalities. In the emergency department (ED), she had a V/Q scan, lower extremity Doppler studies and chest X-ray which were all unremarkable. The patient was subsequently transferred to our institution.

Sixteen hours passed from initial presentation at the outside hospital to evaluation at our facility. Vital signs at our institution were within normal limits, with blood pressure 143/94 mm Hg, heart rate 84 beats per minute, body temperature 36.4° C and respiratory rate of 16 breaths per minute. Troponin-T levels were 1.92 ng/mL and subsequently 0.46 ng/mL.

While in the ED that evening, the patient experienced a repeat episode of chest pain (20:50 h) which resolved after one dose of sublingual nitroglycerin. A repeat EKG was obtained after symptoms resolved (21:11 h) and demonstrated sinus rhythm with first degree AV block, abnormal R wave progression and no ST segment or T wave abnormalities. An echocardiogram with Doppler was obtained which demonstrated no wall motion abnormalities with a left ventricular ejection fraction of 65%.

At this time there was no identifiable cause for her AMI or non-ST segment elevation myocardial infarction (NSTEMI), but the most concerning differential diagnosis included coronary artery dissection. The following day the patient underwent coronary angiography which demonstrated no evidence of coronary artery dissection or occlusion (Figure 1A–C). Based on these normal findings, CAV was the diagnosis of exclusion, and we began to treat her with calcium channel blockers, starting her on amlodipine 2.5 mg daily beginning on hospital day 3. On hospital day 3 the patient had a recurrent episode of chest pain which resolved after two doses of sublingual nitroglycerin. Amlodipine was switched to nifedipine XL 30 mg by mouth daily the following day. Repeat EKG showed borderline ST depression with T wave changes (Figure 2) and echocardiogram was unchanged.

Figure 1:

Coronary angiography. (A) RAO cranial view. (B) RAO caudal view. (C) LAO cranial view.

RAO = Right anterior oblique; LAO = left anterior oblique.

Figure 2:

Electrocardiogram after episode of chest pain.

On hospital day 4 the patient again had a repeat episode of chest pain (01:20 h) which subsided with one standard dose of nitroglycerin. At this point it was decided to increase her nifedipine to 30 mg twice a day. The patient suffered a subsequent episode of chest pain that evening (20:40 h) which resolved after two doses of nitroglycerin. It was then decided to add a long acting nitrate, isosorbide mononitrate 30 mg daily.

The patient was discharged on hospital day 6 after suffering no repeat episodes of chest pain with combination nifedipine XL 30 mg twice a day and isosorbide mononitrate 30 mg daily. Antiphospholipid antibodies were within normal limits. All vital signs remained stable throughout her hospitalization. Upon discharge we included delivery precautions to avoid methergine, misoprostol and beta-blockers as these may induce CAV. After discussion with the cardiologists at our institution Valsalva was deemed to be safe in the second stage of labor.

Following hospital discharge, she had continued intermittent chest discomfort, although not as severe as her initial presentation. She required one sublingual nitroglycerin for these episodes in the outpatient setting.

Due to persistent headaches and only mild chest pain, her isosorbide mononitrate was discontinued at 34 weeks. Nifedipine XL dose was increased to 90 mg daily in order to provide pain control while avoiding headaches from the nitrates. She was placed on ambulatory ECG monitoring for 48 h which was unremarkable. Additionally, given her height, arachnodactyly, and recent cardiac events, she was referred to Medical Genetics for an evaluation for Marfan syndrome; she did not meet strict criteria for Marfan but was ultimately diagnosed with mitral valve, aorta, skin and skeletal (MASS) features phenotype, a connective tissue disorder that shares many overlapping features with Marfan syndrome.

At 36 weeks, the patient represented to the hospital with chest pain and shortness of breath and was restarted on isosorbide mononitrate. Her vitals were normal with O₂ saturation of >95%. A V/Q scan was performed and low probability for a pulmonary embolism. Three sets of troponins were negative. Repeat echocardiogram was unremarkable, with an ejection fraction of 60%. Given improvement of symptoms, negative studies and no acute cardiac changes, the patient was discharged home with outpatient follow-up.

After a joint discussion with cardiology, a decision was made to proceed with induction of labor at 36 weeks + 4 days during a period of stability. The patient was monitored with telemetry and induction proceeded misoprostol and a Foley balloon. The second stage lasted 4 min and she had an unassisted vaginal delivery with epidural anesthesia. A healthy baby girl was born weighing 3430 g. The patient had no telemetry events intrapartum or for 48 h postpartum. She was discharged home in stable condition on postpartum day three on nifedipine XL only and followed up with cardiology.

Discussion

We used the terms “acute myocardial infarction”, “myocardial infarction”, “coronary artery vasospasm” and “pregnancy” for our PubMed review. We also evaluated all references in the identified articles. Six cases of AMI in pregnancy due to CAV have been reported as of November 2016, including ours (Table 1). The mean age was 37 and five of six were multigravida patients, none of whom experienced similar episodes in prior pregnancies. Five out of six (83%) cases occurred in the third trimester or postpartum period. The majority of women were healthy. Of those with comorbidities, one had diabetes mellitus, and another was a former smoker with hypothyroidism. All women presented with chest pain, in combination with other symptoms including palpitations, nausea, emesis, or diaphoresis.

The results of laboratory parameters, EKG, echo and coronary angiography for women with AMI due to CAV are summarized in Table 2. All patients had elevated cardiac enzymes: three of six (50%) had elevated CK-MB and five of six (83%) had elevated troponin values. All patients had EKG changes suggestive of ischemia, with four of six (67%) demonstrating ST-elevation. Five out of six patients underwent echocardiography, and four of five echocardiograms demonstrated hypokinesis or wall motion abnormalities. Two out of five demonstrated a diminished ejection fraction, and one echocardiogram was within normal limits. At time of cardiac catheterization, three of six patients had normal coronary angiography and three of six demonstrated evidence of vasospasm.

Treatment and pregnancy outcome data are summarized in Table 3. All patients were treated pharmacologically with a nitrate, and five of six (83%) required the addition of a calcium channel blocker. Of the four cases occurring during pregnancy, two of four (50%) delivered full term, and two of four (50%) delivered preterm. Both of the preterm deliveries were iatrogenic and medically-indicated, one due to preeclampsia, and the other due to multiple recurrent episodes of chest pain. Two out of four (50%) of patients delivered vaginally, and two of four (50%) by cesarean. One cesarean delivery was primary with no attempt at trial of labor. No intrapartum or postpartum complications occurred.

Including one new case, there are six cases of AMI due to CAV in pregnancy in the literature up to now. All patients presented with a combination of chest pain, diaphoresis, nausea and vomiting. As seen in our patient, episodes usually occurred between midnight and early morning. Five cases occurred in the third trimester or postpartum when hemodynamic and hormonal changes are most pronounced. Three cases occurred in the setting of a hypertensive disorder which may be a risk factor for MI in general, but also for CAV related MI. All cases had abnormalities in cardiac enzymes and the EKGs, with some also demonstrating changes in the echocardiograms of varying degrees. All patients received nitrates, and the majority received additionally calcium channel blockers, achieving control of their symptoms. Overall the pregnancy outcomes of all six pregnancies complicated by AMI due to CAV were good, with two iatrogenic preterm births and no significant cardiovascular complications.

Three case reports documented follow-up in the first 6 months after presentation. Iadanza et al. [1] reported after 6 months of follow-up that their patient was still asymptomatic and was continued on therapy with aspirin, ramipril and carvedilol, polyunsaturated fatty acid. Almassinokiani et al. [3] reported “an ECG 3 months after discharge still showed an anteroseptal myocardial infarction. Koneru et al. [5] reported that the patient had a percutenous coronary intervention (PCI) 2 months after her presentation and the second coronary angiogram showed normal coronary arteries. Our patient was followed-up at an outside institution following her discharge from the hospital. She delivered her baby without incident. She was taken off calcium channel blockers, but continues to have symptoms requiring the use of sublingual nitroglycerin.

Although the risk of AMI is increased by three- to four-fold in pregnancy [5], it is still rare, with reports suggesting a frequency of three to 10 cases/100,000 deliveries [6]. AMI during pregnancy was first noted in 1921, with multiple case reports since then. The hormonal and hemodynamic changes that occur during pregnancy may play a role in why AMI occurs. As maternal age increases, so do risk factors associated with cardiovascular disease (CVD) such as hypertension (HTN) and diabetes. CAV is a well-known, albeit a rare reason, for myocardial ischemia. Causes of CAV in pregnancy have been attributed to vascular reactivity to angiotensin II, norepinephrine and endothelial dysfunction [7]. CAV accounts for only 1.8% of pregnancy- related AMIs [5], [7] and 2% of angina cases [3]. Not only is the acute management of the MI important for the mother, but fetal growth should be monitored in light of repetitive attacks of myocardial ischemia [2].

AMI is one of the two most common causes of cardiac death in pregnant women [8]. It is important to recognize the increased risk of cardiovascular events in pregnant women and treat them accordingly. Differential diagnosis may be broad and includes AMI, coronary artery dissection, aortic dissection, hypertensive emergency, pericarditis, pulmonary embolism, pneumothorax, GERD/gastritis and anxiety. Initial diagnostic testing should include laboratory studies to ensure there are no coagulopathies, anemia, platelet abnormalities and to assess for cardiac ischemia. Transthoracic echocardiogram should be performed. CAV may be associated with ST segment elevation, ST segment depression or negative U wave on EKG [5]. Patients presenting with ST elevation should undergo emergent cardiac catheterization with lead shielding per institutional radiation safety guidelines. This is the gold standard for the diagnosis of CAV with the consideration for addition of provocative agents (e.g. ergonovine or acetylcholine). If a patient is diagnosed with CAV, medical therapy is recommended with calcium channel blockers and nitrates if needed.

Patients presenting with AMI, due to any cause, should be evaluated by cardiology and maternal-fetal medicine to ensure optimal diagnosis and treatment of cardiovascular complications in pregnancy. This review demonstrates the importance of performing a catheterization promptly if AMI is suspected, and pregnancy should not deter or delay the procedure. Additionally, hypertensive diseases of pregnancy such as preeclampsia may be interrelated to AMI due to CAV and should be considered during evaluation. Timing and mode of delivery do not need to change from standard obstetric management. Suggested modifications to obstetric care include minimizing use of methergine and misoprostol and beta blockers, which can provoke CAV. Given the intermittent nature of the CAV, a high index of suspicion and prompt treatment should be offered despite normal diagnostic testing as seen in our patient. Appropriate postpartum follow-up among both maternal-fetal medicine and cardiology can help monitor for continued symptoms and assess these patients’ outcomes. Long-term follow-up of these patients will assist in the development of guidelines in the management of this condition in future pregnancies.