Menstruation-Associated Spontaneous Coronary Artery Dissection

ABSTRACT: Eighty percent of all spontaneous coronary artery dissections occur in women. A third of these occur in pregnancy or post-partum period and a variation in hormonal levels is thought to play an etiologic role. It has been suggested that the menstrual period, a low-estrogen state, may be associated with spontaneous coronary artery dissections. We report a case of menstruation-associated spontaneous coronary artery dissection and review the available literature. J INVASIVE CARDIOL 2010;22:E183–E185 Key words: SCAD; M-SCAD ———————————————————————————— Eighty percent of all spontaneous coronary artery dissections (SCAD) occur in women.¹ A third of these occur in pregnancy or post-partum period and a variation in hormonal levels is thought to play an etiologic role. It has been suggested that the menstrual period, a low-estrogen state, may also be associated with SCAD.² We report a case of menstruation-associated spontaneous coronary artery dissection (M-SCAD) and review the available literature. Case Report. A 37-year old female with history of controlled hypertension developed acute onset left-sided exertional chest burning radiating to her left arm. The discomfort was persistent and prompted the patient to present to emergency department (ED). Her examination was within normal limits, as was her initial electrocardiogram (ECG). The burning in her chest resolved spontaneously and she decided to leave against medical advice. Later that night the chest pain recurred and she returned to ED. This time her ECG showed new symmetric T-wave inversions in anterolateral and inferior leads. Initial troponin-T level was elevated at 0.12 ng/ml. She was started on aspirin, metoprolol, enoxaparin and eptifibatide. Her pain was relieved with nitroglycerin. She was transferred to our hospital for coronary angiography. The review of systems was significant only for the fact that the patient was near the end of her menstrual period. In addition to hypertension, her past history revealed elevated C-reactive protein and homocysteine levels. Her outpatient medications included hydrochlorothiazide, daily aspirin, and folic acid. She was a non-smoker and denied using drugs, including cocaine. There was a strong family history of premature coronary artery disease (CAD); her mother died from myocardial infarction (MI) at age 50 and her father died from MI at age 48. The patient was an obese, African-American female who appeared comfortable. She had a blood pressure of 155/83 mmHg and a pulse of 64 beats/min. There was no jugular venous distension. Her lungs were clear. Normal S1 and S2 sounds were heard with no murmurs, rubs, or gallops. The rest of her physical examination was unremarkable. Coronary angiography revealed angiographically normal left main coronary artery. The left anterior descending artery (LAD) had a change in caliber after the first septal perforator branch, amounting to approximately 30% stenosis (Figure 1). The first diagonal branch had 50–75% ostial stenosis and, what later became apparent after a closer analysis, a faint dissection flap seen in the lumen. The distal LAD had moderate diffuse disease. The left circumflex artery (LCx) was angiographically normal. The proximal portion of the dominant right coronary artery (RCA) had a 50% stenosis. The mid and distal RCA showed spontaneous dissection extending into the posterior descending artery (PDA) (Figures 2–4). There was a 90% ostial stenosis of the PDA. There was TIMI grade 3 flow throughout the right coronary artery. Left ventriculogram revealed preserved left ventricular systolic function with inferoapical dyskinesis. At the time of coronary angiogram, the patient was completely asymptomatic and hemodynamically stable. The dissection was not thought to be amenable to percutaneous intervention and the patient was continued on medical treatment. Within 24 hours she developed severe chest pain. The ECG now showed ST-segment elevation in the inferior leads. Emergent coronary angiography revealed persistent dissection in the RCA. The left coronary system appeared similar to the first catheterization. It was thought that the dissection flap in the RCA was dynamic, intermittently compromising the flow to distal RCA. Due to persistent symptoms and EKG abnormalities emergent coronary bypass grafting was performed. Dissections in the distal RCA, PDA and the LAD were confirmed during surgery. The patient underwent left internal mammary artery (LIMA) grafting to the LAD, saphenous vein grafts to acute marginal, diagonal, and the PDA. Postoperatively, she recovered uneventfully. A transthoracic echocardiogram revealed an ejection fraction of 60% and no wall motion abnormalities, aside from septal contraction abnormality, possibly due to cardiac surgery. She was discharged on postoperative day 5 and has done well since then. Discussion. Eighty percent of all spontaneous coronary artery dissections occur in women.¹ Spontaneous coronary artery dissections are broadly divided into three main categories: those related to underlying coronary atherosclerosis, idiopathic, and pregnancy-associated.³ Although our patient did have coronary artery disease, its extent was not sufficient to explain multivessel dissections occurring simultaneously and involving both the left and right coronary systems. Thus, we consider our case to be another incidence of M-SCAD. Unlike pregnancy-associated coronary dissection, where over a hundred cases have been described, there are only a few reported cases of M-SCAD so far (Table 1). Nevertheless, it may be important to define M-SCAD as a distinct entity, similar to P-SCAD. All previously described cases of M-SCAD involved left coronary system only. Our case is the first reported case of M-SCAD involving both left and right coronary systems. It is notable that most women were older (age 37–49). This is similar to P-SCAD, where older age may be a risk factor, as 70% of women with P-SCAD are over 30 years of age.⁵ We did come across a case in the literature where a 24-year-old woman had a SCAD 1 day after cessation of menses, which could be considered M-SCAD.⁴ Variations in hormone levels have previously been proposed as possible etiology of spontaneous coronary dissections. During pregnancy, altered endocrine status may cause changes in the arterial wall, including fragmentation of reticulin fibers, loosening of ground substance, and smooth muscle hypertrophy.⁶ These changes may play a role in the pathogenesis of SCAD. Other evidence to support hormonal theory are SCAD cases associated with the use of oral contraceptives.^7,8 The relationship between menses and CAD has been studied previously. Anginal attacks in women with variant angina peak at the onset of menses, when estrogen levels are at their lowest.⁹ Low estrogen levels during menses may trigger acute coronary syndrome (ACS) and transient estrogen depletion around the time of menstruation may be clinically significant.¹⁰ When 27 premenopausal women who had ACS were examined, all acute coronary events occured in the first half of the menstrual cycle, i.e., during menstruation or soon after.¹⁰ It has been postulated that decrease in estrogen levels after ovulation may have delayed effect, which then manifests as a coronary event at the time of menstruation.¹⁰ Stress testing premenopausal women during menstruation may provide better sensitivity for CAD.¹¹ During menstruation women with preexisting CAD develop exercise-induced ST-segment depressions more rapidly.¹² In addition, healthy females undergoing stress testing during menstruation have more false positive findings.¹³ Hypertensive women have higher blood pressure during the luteal phase.¹² Highest levels of renin, angiotensin II, and aldosterone are also found during the luteal phase of the menstrual cycle.¹⁴ Levels of endothelin-1, a powerful vasoconstrictor, are highest during menstruation¹⁵ and nitric oxide levels are lowest.¹⁶ We suspect that pathologically, M-SCAD is similar to P-SCAD, in which the dissection plane is in the outer third of tunica media of the arterial wall, usually originating within 2 cm of aortic ostium.⁶ An intramural hemorrhage, possibly preceded by intimal tear, leads to a hematoma which compresses the true lumen, compromising blood flow. Most dissections will extend distally. The definitive diagnosis is made by coronary angiography, which may show a dissection flap and external compression of the true lumen. In some cases, the initial angiogram may be normal¹⁷ and intravascular ultrasound may be helpful to uncover occult dissection. In addition, intravascular ultrasound may identify the true lumen and guide angioplasty and stenting.¹⁸ A follow-up catheterization is often needed to assess further extension of dissection and identify two-step dissections. Multidetector computerized tomography may also be useful for diagnosis and follow up.¹⁹ Management of M-SCAD and P-SCAD is not well defined. Stable patients with single-vessel dissection, without progression or hemodynamic compromise, and without left main coronary artery involvement or otherwise large area of myocardium in jeopardy, could be managed medically.⁶ Many of these heal spontaneously. While no specific medical regimen exists, aspirin, clopidogrel, heparin, beta-blockers, and ACE inhibitors have been used.^5,6,20 Thrombolytics may cause progression of intramedial hemorrhage, extension of dissection, and further compression of the true lumen.²⁰ Percutaneous coronary intervention with stenting has been used successfully in women with long single vessel dissections and multivessel dissections with hemodynamic compromise.⁶ Stenting allows pinning the dissection flap and provides a buttress against compressive forces of the intramural hematoma.¹⁸ It is not established whether stenting just the inlet of the dissection is more effective than stenting its entire length. Whether DES have any advantage over BMS in treatment of SCAD is also not known. Complications encountered with stenting of SCADs include extrusion of the hematoma proximally or distally, which may propagate dissection further. Inadvertent wiring and stenting the false lumen results in obliteration of the true lumen and is a catastrophic event. To prevent this complication, IVUS can be used to reliably identify the false lumen.¹⁸ Coronary artery bypass grafting is usually indicated for patients with left main coronary artery involvement, multivessel dissections, failed medical or percutaneous therapy, and evolving dissections with significant hemodynamic compromise.^5,6 Bypass surgery aims to place anastomosis beyond the dissection. If that is not possible, incorporating both true and false lumens into the anastomosis will reestablish true luminal flow.²¹ Cardiac transplantation has successfully been performed in a few cases with severe left ventricular dysfunction.⁶ Most of the literature on SCAD in women focused on P-SCAD. There are no prospective trials given the rarity of this condition. Observational data are comprised of isolated case reports, small series, and systematic reviews. Prior to 1999 the mortality was reported to be 38%, however, 0% mortality was noted in patients who survived the acute phase and were treated by medical, interventional, or surgical approach.⁶ A recent review of 25 P-SCAD cases published after 1999 reported 100% overall survival, thought to be due to heightened awareness, more rigorous ACS guidelines, and advanced medical and interventional strategies.²²Conclusion. In conclusion, we report a case of M-SCAD involving both left and right coronary systems. Premenopausal women who present with symptoms suggestive of ischemia or acute coronary syndrome should be asked about their menstrual history. A possibility of M-SCAD should be considered if the patient is perimenstrual or actively menstruating and prompt diagnosis and treatment should be initiated. The menstrual period may indeed prove to be a “vulnerable period” in susceptible individuals, predisposing them to SCAD. Acknowledgment. We would like to thank our librarian, Dolores Moran, for her assistance with literature search.

References

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———————————————————————————— The authors report no conflicts of interest regarding the content herein. Manuscript submitted December 8, 2009, provisional acceptance given January 4, 2010, final version accepted February 11, 2010. Address for correspondence: Leo Marcoff, MD, 4755 Ogletown-Stanton Rd., Room 2E99, Newark, DE 19718. E-mail: lmarcoff@christianacare.org