Spontaneous Multivessel Coronary Artery <br />
Dissection in a Long-Distance Runner <br />
Successfully Treated with Oral Antiplatelet <br />
T

Spontaneous coronary artery dissection is an unusual cause of acute coronary syndrome resulting in a spectrum of presentations from non-Q wave myocardial infarction to sudden death or cardiogenic shock. There is no clear consensus therapy for spontaneous coronary artery dissection, and the diagnosis is often unknown until the time of coronary angiography. The treatment strategies reported in the literature are as varied as the presenting scenarios. Mechanical methods including percutaneous coronary intervention, coronary artery bypass surgery and cardiac transplant have been utilized.1–3 In addition, novel medical regimens from immunosuppression to intravenous glycoprotein IIb/IIIa inhibitor therapy have also been attempted.4,5 We report a case of multivessel spontaneous coronary artery dissection successfully managed with medical therapy, and a review of the current literature on spontaneous coronary artery dissection. Case Report. A 37-year-old previously healthy caucasian female initially presented to an outside hospital with 40 minutes of severe substernal chest burning associated with bilateral arm radiation and diaphoresis shortly after a 10-mile training run. During the 10 weeks prior to presentation, the patient had been actively training for the Chicago Marathon. Her longest run to date was 18 miles. The patient’s past medical history was significant for a normal vaginal delivery 20 months prior and no known cardiac risk factors or history of vasculitis. In addition, the patient had no family history or physical features suggestive of connective tissue disorders, such as Marfan’s or Ehler-Danlos syndromes. The patient’s social history revealed no tobacco, alcohol or illicit drug use. The admitting ECG revealed sinus bradycardia at a rate of 52 beats per minute with T-wave inversions in the inferior-lateral leads. The patient was subsequently admitted to the CCU, where she was treated as an acute coronary syndrome and received aspirin and therapeutic doses of enoxaparin. An intravenous glycoprotein IIb/IIIa inhibitor was not utilized. A beta-blocker was not given due to baseline bradycardia. A 2-dimensional echocardiogram with color Doppler performed on admission demonstrated normal left ventricular systolic function without any valvular abnormalities. Serial cardiac markers revealed a non-Q wave myocardial infarction with a peak troponin I of 3.5 ng/ml (normal: 0–0.5 ng/ml). Left heart catheterization, performed on the following day, revealed multivessel coronary artery dissections in the following arteries: mid left anterior descending artery, distal first diagonal and mid-distal posterior descending artery (Figure 1). The remaining coronary arteries were angiographically normal and TIMI 3 flow was present in all vessels. Left ventriculography demonstrated mild anteroapical hypokinesis with overall preserved left ventricular function. Given the resolution of chest discomfort and presence of TIMI 3 flow, the patient was discharged on day 2 with the following medical regimen: clopidogrel 75 mg daily, aspirin 325 mg daily, and sustained release metoprolol 25 mg daily. One month later, the patient was evaluated as an outpatient at our institution. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor and anti-nuclear antibodies were found to be within normal limits. A tissue active ACE inhibitor, ramipril, was added to the medical regimen. A 7-month follow-up angiogram to evaluate the progression or stabilization of the coronary dissections was recommended. The subsequent left heart catheterization revealed angiographically normal coronary arteries with normal left ventricular systolic function with an ejection fraction of 60% (Figure 2). At 1-year follow-up, the patient remained symptom-free while returning to a regular running program of 3–5 miles per day. Marathon training has been discouraged. In addition, the patient had an exercise stress echo that demonstrated baseline normal left ventricular systolic function with an ejection fraction of 60%. She completed 16 minutes of the Bruce protocol without any ECG changes or echocardiographic evidence of exercise-induced ischemia. Discussion. This is the first reported case of non-pregnancy related spontaneous multivessel coronary artery dissection with complete angiographic resolution on oral antiplatelet agents. In general, coronary artery dissection can occur spontaneously, or as a result of aortic dissection, blunt chest trauma, coronary artery bypass grafting, cardiac catheterization or coronary angioplasty.6 Spontaneous coronary artery dissection is an unusual cause of acute coronary syndrome encompassing a full range of presentations from non-Q wave myocardial infarction to sudden death or cardiogenic shock. Approximately 3 out of every 4 reported cases occur in women.6 The peri partum period is a particularly vulnerable time for spontaneous coronary artery dissection and has been reported to be associated with 31% of the cases seen in women.6 It is thought that the hormonal changes seen during pregnancy cause a loss in structural integrity of the arterial wall.7 In addition to the peri partum period, spontaneous coronary artery dissections have been described in association with a variety of clinical factors and conditions: coronary atherosclerosis, Marfan’s syndrome, Kawasaki’s disease, sarcoidosis, fibromuscular dysplasia, vigorous exercise, poorly-controlled hypertension and oral contraception.2,8,9 A spontaneous coronary artery dissection affecting more than one vessel is rare. Current review of the literature reveals 5 cases of multivessel spontaneous coronary artery dissections.3,4,7,8,10 All five cases consisted of women with ages ranging from 29–41 years old. Three of the 5 cases occurred during the peri partum period. One patient was a postmenopausal woman, while the remaining case was thought to be provoked by poorly controlled hypertension. Treatment strategies for these multivessel cases included percutaneous coronary stenting, coronary artery bypass surgery, cardiac transplantation and immunosuppressive medical therapy. Coronary artery bypass surgery was successfully performed in 2 patients who were clinically stable at follow-up dates ranging from 7 days to 36 months.7,8 One patient underwent multivessel coronary artery stent implantation and was symptom-free at 2-week follow-up.18 The patient who received immunosuppressive therapy was also clinically stable at 94 days.4 The last patient, who presented in cardiogenic shock and initially failed coronary artery bypass surgery, was eventually successfully transplanted and remained clinically stable at 34 days.3 Pathological examination of the original coronary arteries from the transplanted patient found foci with loss of normal structure, intimal and medial hyperplasia alternating with medial attenuation, which was characterized as fibromuscular dysplasia.3 The increased hemodynamic shear forces added to the already augmented coronary blood flow resulting from exercise are thought to contribute to dissection formation in predisposed arterial walls. Review of the literature reveals 5 cases of spontaneous coronary artery dissection associated with exercise.1,2,5,9,11 Similar to the present case report, two of the 5 cases occurred in active long distance runners2,5 and 3 of the 5 cases occurred in women.5,9,11 The left main artery was involved in 2 cases, the left anterior descending in another 2 instances, and the left circumflex in one case. Treatment strategies in this exercise-related cohort consisted of emergent coronary artery bypass surgery in 3 patients, percutaneous stent placement in another, and intravenous glycoprotein IIb/IIIa inhibitor therapy in the last. The stented patient was asymptomatic at 3-month follow-up.1 The patient who was treated with intravenous glycoprotein IIb/IIIa inhibitor therapy was clinically stable at the time of discharge.5 Two of the 3 patients who underwent coronary artery bypass surgery were doing well at follow-up ranging from 1 to 4 years.2,9 The remaining patient died of electromechanical dissociation following coronary bypass surgery. An autopsy on this death found extensive dissection of the left coronary artery system with compressive occlusion of the true lumen. Furthermore, the dissection plane was located between the outermost media and adventitia.11 The long-term safety of resuming vigorous physical activity after surviving spontaneous coronary artery dissection related to exercise is uncertain. Only 1 of the 4 surviving exercise-related cases report the patient returning to exercise. This patient who resumed running was initially treated with bypass surgery, and remained symptom-free at 4-year follow-up. Moreover, an exercise stress test performed at 2-year follow-up was negative for ischemia after having completed stage 4 of the Bruce protocol.2 The post-dissection exercise status of 2 of the remaining 3 patients is unknown. The last case of exercise-related dissection reported that the patient returned to a sedentary lifestyle. Given that there is no clear consensus therapy for spontaneous coronary artery dissection, coupled with the uncertain diagnosis at the initial presentation, there have been several medical strategies reported in the literature. The more recent case reports1,5,12 have initially opted for conventional acute coronary syndrome therapy consisting of aspirin, beta-blockers and heparin, with or without nitrates. In addition, other novel medical therapies have been attempted. Based on prior findings of periadventitial eosinophilic inflammation in autopsy findings of spontaneous coronary artery dissections, an immunosuppressive regimen of prednisone, cyclophosphamide coupled with aspirin 81 mg daily and therapeutic warfarin has been successfully utilized, resulting in normal angiographic coronaries at 94 days.4 Intracoronary tissue-specific plasminogen activator was given in another patient, which resulted in a new retrograde coronary artery dissection that extended proximally to the aorta, requiring emergent coronary artery bypass surgery.11 There are 3 reports of systemic thrombolytic use when the initial presenting electrocardiogram revealed localized ST-segment elevation.5,8,12 All three patients had recurrent angina prompting cardiac catheterization, at which time the diagnosis of coronary artery dissection was made. Two of the 3 patients eventually underwent successful coronary artery bypass surgery. The remaining patient was treated with intravenous glycoprotein IIb/IIIa inhibitor therapy with the intention of stent placement in the dissected artery. At 20 hours after the diagnostic catheterization, there was complete angiographic resolution of the dissection and no percutaneous mechanical intervention was required.5 Including the current case, there have been 3 reports of complete angiographic resolution of coronary artery dissections.4,5 The first case successfully used prednisone, cyclophosphamide, aspirin 81 mg and therapeutic warfarin.4 Intravenous glycoprotein IIb/IIIa inhibitor was utilized in the second instance.5 The current patient received aspirin 325 mg and clopidogrel 75 mg daily. Autopsy findings in earlier cases of spontaneous coronary artery dissection resulting in sudden death report intramural thrombus accumulation in the false lumen with consequent compressive occlusion of the true vessel lumen.13 It can be theorized that the antiplatelet effects of aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitor used in these 3 instances minimized the thrombus accumulation within the false lumen while allowing for normal vessel healing. Ultimately, the therapeutic strategy chosen for spontaneous coronary artery dissections will depend on the patient’s clinical condition and anatomic considerations. Mechanical interventions such as coronary artery bypass surgery, percutaneous coronary stent implantation and cardiac transplantation should be considered in persistently symptomatic or hemodynamically unstable patients. Nonetheless, oral antiplatelet therapy with aspirin and clopidogrel can be successfully used as a therapeutic option.

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