Spontaneous Coronary Artery Dissection Related to Menstruation

Coronary artery disease (CAD) has been recognized as the leading cause of mortality in women. Previously, it had been thought that estrogen provided a protective CAD effect, explaining the later development of disease in women. The Women’s Health Initiative was stopped prematurely in 2004, as it showed adverse effects of estrogens on heart disease. Estrogen’s effect on the vasculature, especially the coronary bed, has not been completely determined.
Spontaneous dissection of the coronary arteries was first described in 1931. Since that time, a number of case reports have shown a relation to hormonal surges, i.e., oral contraceptive use, pregnancy, an so forth. The etiology is unclear, but has been related to inflammatory cell infiltrate in the arterial wall, as well as an increase in shear forces and vascular changes seen with hormonal fluctuation.
We present a case of a 44-year-old female with acute dissection of the left coronary system that occurred during menstruation. She had no significant cardiac risk factors, and was in good health prior to the acute event. We hypothesize that hormonal changes associated with menstruation may have contributed to this spontaneous coronary dissection.

Case Report

A 44-year-old female presented to an outside emergency department after developing acute-onset substernal chest pain with radiation to the back and neck while driving home from work. There was associated nausea and profound diaphoresis. She had no personal or family history of coronary artery disease. The patient was a lifelong nonsmoker, nondiabetic, with a normal lipid profile in the prior 6 months. She had no history of vasculitis or Marfan’s disease and denied any recent fever, infection, arthralgias or change in her overall health. She had a history of 2 uncomplicated pregnancies and no miscarriages. Her only significant history was of depression that was treated with 2 different antidepressants. Her menstrual period had started 3 days prior to the event. Electrocardiography (ECG) on presentation at the outside hospital showed sinus rhythm at 80 beats per minute, with Q-waves in V2–V3 and 1–2 mm of ST-elevation and reciprocal ST-depression in leads III and AvF.
After treatment with aspirin, sublingual nitroglycerin and intravenous metoprolol in the emergency department, her pain had diminished. Repeat ECG 45 minutes after arrival showed ST-segment depression in leads V2–V3, but was otherwise unremarkable. She remained stable in the emergency department, and was observed for over an hour while cardiac enzymes were evaluated. Since the ECG had improved, the emergency department physician considered several diagnoses including pericarditis and anxiety. One hour from arrival at the emergency department, the patient had residual discomfort and cardiac enzymes returned with elevated CK and CK-MB fraction, but negative troponin. The patient was transferred via helicopter to our institution for further evaluation.
On presentation, the patient was diaphoretic, severely fatigued, and mildly hypotensive with minimal chest pain. She was taken directly to the cardiac catheterization laboratory due to suspicion of acute coronary syndrome. Two initial diagnostic images were taken of the right coronary artery (RCA), which were normal. Engagement of the left main coronary artery (LMCA) was performed under direct fluoroscopy, with initial contrast injection in the left coronary cusp. Subsequent images demonstrated minimal flow in the left coronary system.
Initial differential diagnosis included acute LM thrombosis that subsequently occluded both the left anterior descending (LAD) and circumflex (Cx) arteries, or spontaneous dissection. The patient was hemodynamically stable, and there was a trickle of flow seen into the distal LAD (Figures 1 and 2). Initial suspicion was of acute thrombosis, thus intracoronary abcixmab was administered. This improved flow in the Cx and revealed dissection throughout the left circumflex (LCx) from the ostium to the distal vessel with what appeared to be dissection back into the LMCA in the caudal images. The on-call surgeon was contacted to mobilize the operating room. Placement of a soft-tipped guidewire into the LAD was successful, with improvement to TIMI 2 flow showing spiral flow of contrast into the more distal LAD and second diagonal branch. A stent was placed in the proximal LAD, which helped to improve flow. The patient became progressively hypotensive and lethargic, with decreased oxygen saturation during the course of the procedure. Because of the appearance of a hazy area in the proximal LCx and a probable dissection flap, the decision was made to place a stent in the proximal LCx to maintain vessel patency. Before the guidewire was inserted, the LCx reoccluded. A guidewire was passed into a large marginal branch and a stent was placed in the proximal vessel. Despite improved flow in both vessels, the patient’s hemodynamic status continued to worsen. Follow-up imaging showed reocclusion of both arteries, with dissection extending back into the LMCA.
An intra-aortic balloon pump had been inserted prior to percutaneous coronary intervention, and intubation was required for respiratory distress. The patient was taken to the operating room emergently. She was placed on bypass and underwent saphenous vein grafting to the LAD and Cx arteries. There was severely reduced ventricular function postoperatively, which required a significant amount of time weaning from bypass, as well as high doses of pressor agents. The surgeon did not palpate any significant atherosclerosis in the coronary arteries, and there was no evidence of thrombus when either artery was cannulated.
The patient’s recovery was uneventful, and she left the hospital on day 7. An echocardiogram performed the day prior to discharge showed a near-normal ejection fraction of 50%, with very mild anterior hypokinesis. At follow up 3 months later, the patient was back to work and normal activities.

Discussion

Since first described in the literature in 1931, there have been nearly 200 case reports of spontaneous coronary dissection. Many relate to women in the peri- or postpartum period, or are associated with oral contraceptive use. The majority have acute onset of chest pain with minimal or no cardiac risk factors, and spontaneous coronary dissection is reported in younger-aged women who are premenopausal. Predominantly, the LAD is involved (72%), with the other vessels less frequently so: left main (4–8%), RCA (20%), and LCx (4%). Sudden cardiac death has been reported in up to 50% of women with spontaneous dissection, especially of the left main artery. Multivessel involvement is uncommon, but has been reported.^1–7
The mechanism of spontaneous dissection is not entirely known. Rather than intimal tear, as is common in iatrogenic dissection, many patients demonstrate rupture into the intima with compression of the vessel’s true lumen. Increased circulating levels of eosinophils, which play a role in uterine involution postpartum, has been speculated to play a role in spontaneous dissection, and has been demonstrated in autopsy studies.
Numerous studies have examined the relationship of hormone levels to vascular tone in women during their menstrual cycle. Women display increased vascular tone around the time of menstruation — a higher degree of vascular tone than aged-matched men. In women with known coronary disease, ischemic episodes increase when hormone levels are at their lowest.^11–17
Fractional flow reserve (FFR) has been used to measure blood flow in the coronary arteries at different times of the menstrual cycle in women with known CAD. A statistically significant decrease in coronary blood flow during the time of the lowest level of circulating hormones has been shown, while the highest levels of blood flow occurs when hormone levels are at their peak. Studies have also shown decreases in blood flow in the peripheral and carotid arteries.¹¹
Stress testing performed at different phases of the menstrual cycle in women with known CAD have demonstrated a significant change in time-to-onset of angina or ischemic ECG changes at the time of menstruation versus mid-cycle (290 seconds vs. 418 seconds on the treadmill), consistent with FFR findings.¹²
To our knowledge, there is only one other report consisting of two women who had spontaneous dissection that was related to their menstrual period.⁸

Diagnosis. A high level of suspicion and rapid evaluation of the coronary anatomy is essential to survival in spontaneous dissection. Many patients present with typical signs of myocardial infarction, as well as ECG changes, but female gender and young age may cause a delay in the correct diagnosis while other causes of chest pain in this young population are evaluated.²⁶ Computed tomography (CT) has been used to diagnose a patient with a coronary dissection who presented to an emergency room with chest pain symptoms.¹⁸ With the improvement in speed and resolution of 64-slice CT, rapid diagnosis in the emergency department may be possible for this as well as other noncardiac vascular problems such as aortic dissection and pulmonary embolism. However, urgent coronary angiography for definitive diagnosis and potential treatment likely remains the standard method.
Treatment. The reports in the literature on treatment options are varied and mostly anecdotal. As expected with such rare events, there are no randomized trials. There have been reports of conservative medical management and observation, antiplatelet medications (heparin, low molecular-weight heparins, glycoprotein IIb/IIIa inhibitors), thrombolytics, PCI and coronary artery bypass graft surgery. No treatment consensus has been identified. PCI has been reported successfully in patients with isolated LAD or RCA lesions.^{19–24,26,27}
Due to the extensive dissection throughout the left coronary tree, our patient was best managed surgically. Surgery was performed after abciximab administration, and significant bleeding necessitating transfusion intraoperatively was required. Surgical success was due to timely diagnosis and rapid treatment once the patient had been transferred.

Conclusion

Spontaneous coronary dissection is a rare event most often seen in young women with few risk factors. It may occur at any time of low levels or rapidly declining levels of circulating estrogens such as pregnancy or during a menstrual cycle. The effects can be devastating, with high rates of morbidity and mortality in this young group of patients. Our case illustrates that a high level of suspicion should be maintained in pre-menopausal women who present with typical symptoms, even in the absence of CAD risk factors.

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