ABSTRACT: Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome in young healthy females, with pregnancy and the use of oral contraceptive pills as recognized predisposing factors. We present two cases of acute myocardial infarction in two young females without significant risk factors and review the literature on spontaneous coronary artery dissection including diagnosis and treatment options. Acute myocardial infarction in a young healthy female without significant traditional risk factors is uncommon. Spontaneous coronary artery dissection, though an infrequent cause of acute myocardial infarction, is an increasingly recognized etiology in young, otherwise healthy females. The incidence of spontaneous coronary dissection is likely underestimated considering the high rate of sudden death (up to 50%) in affected patients.1 A meticulous literature search revealed occasional case reports linking spontaneous dissection with the use of oral contraceptive pills2–5 and pregnancy.6,7 We report two cases of acute myocardial infarction involving the right coronary artery (RCA) and the left anterior descending artery (LAD) in two healthy young females without significant traditional risk factors. Case Reports Case 1. A 26-year-old Caucasian female with a 10-year history of oral contraceptive use and mild childhood asthma presented to a community hospital with acute onset of left-sided chest pain of 2 1/2 hours’ duration. She had no previous history of chest pain and no family history of coronary artery disease. She smoked 10 cigarettes a week for approximately 10 years and had no history of drug abuse. The electrocardiogram (ECG) showed inverted T-waves and pathological Q-waves in the inferior leads. Her serum troponin concentration peaked at 5.94, and her serum beta HCG was negative. Chest computerized tomography (CT) showed no evidence of pulmonary embolism or aortic dissection. She was treated with aspirin and transferred to our tertiary care facility for further management. On arrival to our facility, she was asymptomatic. Coronary angiography showed localized dissection of the posterolateral branch of the RCA and a distal filling defect suggestive of thrombus (videos 1 and 2). The other coronary arteries were angiographically normal. Left ventriculography showed inferior akinesis with an ejection fraction of 60% (videos 3 and 4). On arrival to the coronary care unit, her blood pressure was 106/70 mmHg and her heart rate was 75 beats/minute. Physical examination was notable for normal jugular venous pressure and normal heart sounds with no gallops or murmur. The rest of the physical examination was normal. The laboratory results were within normal limits except for elevated cardiac markers. A urine toxicology screen was negative. Serum tests for connective tissue diseases, systemic vasculitis and hypercoagulable states were negative. She was treated with aspirin, metoprolol, atorvastatin and nitroglycerin. The patient had an uneventful hospital course with no recurrent chest pain. She was advised to refrain from cigarette smoking and oral contraceptive pill use. She was discharged in stable condition on aspirin, metoprolol, atorvastatin and sublingual nitroglycerin. She was readmitted a week later for recurrent chest pain with a normal 12-lead ECG and cardiac enzymes. Coronary angiography showed no change from the previous angiogram, with thrombolysis in myocardial infarction (TIMI) 3 flow in the RCA. She was managed medically and subsequently discharged in stable condition. Case 2. A 24 year-old obese African-American female with a history of asthma presented to our tertiary facility with acute onset of substernal chest pain a few minutes after waking. She experienced similar chest pain, but less severe, for approximately 9 months prior to presentation. Her social history revealed that she occasionally smoked marijuana and smoked a pack of cigarettes per day for approximately 8 years. She had just finished menstruation a day prior to presentation and denied recent oral contraceptive use. Her blood pressure was 139/82 mmHg and her heart rate was 53 beats per minute. A physical examination was otherwise normal. An ECG showed ST-elevation in the anterolateral leads with reciprocal depression inferiorly consistent with acute myocardial infarction. Her initial troponin was 0.14 and the serum beta HCG was negative. Coronary angiography showed dissection of the proximal LAD with probable thrombotic occlusion of the mid LAD (video 5). The other coronary arteries were angiographically normal. Bare-metal stents were placed in the proximal and mid-LAD arteries. During the case, a dissection flap appeared to propagate proximally into the ostium of the left circumflex artery and further intervention was abandoned. Our impression was that the patient’s vascular substrate was so poor that further intervention or stenting might result in further propagation of the dissection. Echocardiography revealed septal and anterior wall hypokinesis, anterolateral akinesis, mild concentric left ventricular hypertrophy and an ejection fraction of 50%. The laboratory results were within normal limits except for elevated cardiac markers. A urine toxicology screen was negative. Serum tests for connective tissue diseases, systemic vasculitis and hypercoagulable states were negative. She was treated acutely with aspirin, unfractionated heparin, eptifibatide, beta blockade and nitroglycerin. The patient had an uneventful hospital course except for one episode of chest pain with a normal ECG. She was advised to refrain from cigarette smoking, oral contraceptive use and future pregnancy. She was discharged in stable condition on aspirin, clopidogrel, metoprolol, atorvastatin, lisinopril and nitroglycerin as needed. On follow-up visits, the patient continues to experience angina with minimal exertion. Discussion. In 1931, Pretty described spontaneous coronary artery dissection (SCAD) discovered in the post-mortem examination of a 42-year old female with chest pain and sudden cardiac death.8 Subsequently, other cases have been reported.2–7 The incidence of SCAD is difficult to determine because of the high rate of sudden cardiac death and underdiagnosis in affected patients,1 though it has been reported to be responsible for 0.1% to 1.1% of acute myocardial infarctions.9–11 SCAD is more common in females than males,12–14 with pregnancy and the early puerperium as recognized predisposing factors.12,14 The physiologic and hormonal changes that occur in pregnancy may cause medial dissection of the coronary artery through impairment of collagen synthesis, proliferation of myocytes, and alteration in the mucopolysaccharide and protein content of the media. The increased blood volume and cardiac output that accompany pregnancy are thought to facilitate intimal rupture and medial dissection.12,14 When SCAD occurs in females, the left coronary artery is involved in 66–75% of cases,1,10,15 whereas in males, it affects the right and left coronary arteries equally.1,10,15 The precise mechanism of SCAD has not been fully elucidated. Various pathogenetic mechanisms have been proposed. Robinowitz et al found eosinophilic infiltrates in the adventitia of 43% of patients with SCAD and postulated that focal inflammatory processes and proteolytic enzymes released by eosinophils lead to coronary dissection.16 Other proposed mechanisms of SCAD include rupture of an atherosclerotic plaque or vasa vasorum, an underlying connective tissue disorder, cystic medial necrosis and increased shear stress.1,15,16 The role of conventional risk factors in SCAD has not been established, although an association with smoking and hypertension14 has been suggested. SCAD has been reported to occur with exercise,17 menstruation,18 sleep deprivation,19 weight lifting,20 cocaine abuse,21 cyclosporine use,22 and protracted sneezing.23 SCAD has also been reported in patients with Marfan’s syndrome,24 Ehlers-Danlos syndrome,25 polyarteritis nodosa26 and systemic lupus erythematosus.27 Finally, SCAD has been reported in patients without any identifiable predisposing factors.13,28,29 A potential relationship between SCAD and oral contraceptive pills has been reported in 5 patients,2–5 aged 28–50 years, only one of whom smoked. Three presented with an ST-segment elevation myocardial infarction and the other two had a non-ST-segment elevation myocardial infarction. The LAD was the infarct-related artery in all of these cases; 1 had multivessel involvement. Three of the patients were successfully treated medically. One patient required coronary artery bypass surgery after failed percutaneous coronary artery intervention, and another required cardiac transplantation due to refractory cardiogenic shock. Patients with SCAD may present with unstable angina, myocardial infarction, cardiogenic shock or sudden death.14,24,30,31 Alternatively, SCAD may be found incidentally during post-mortem examination or coronary angiography. In cases where angiographic findings are difficult to interpret, intravascular ultrasound has been used to confirm the diagnosis.32 The optimal treatment of SCAD is controversial, but probably should be guided by the patient’s clinical presentation and hemodynamic condition, the location and magnitude of the coronary dissection and the number of vessels affected.1,15,16 Medical therapy including beta adrenergic blockade to control heart rate and blood pressure, aspirin to prevent thrombosis, and a vasodilator to prevent vasospasm are appropriate for hemodynamically stable patients with limited coronary dissection, as in the case of our first patient. The role of anticoagulation is unknown, although complete angiographic resolution of SCAD has been reported in a patient treated with enoxaparin and aspirin.33 The role of statins and potent antiplatelet agents (e.g., clopidogrel and glycoprotein [GP] IIb/IIIa inhibitors)30,35 has not been established, but the latter may be deleterious. In patients with acute myocardial infarction, GP IIb/IIIa inhibitor infusion has led to cardiac tamponade.39,40 Thrombolytic therapy, though beneficial in some patients,14,15 may cause propagation of the dissection and consequent acute deterioration in the patient’s condition.36,37 Patients with recalcitrant chest pain from persistent impairment of coronary blood flow should be considered for stent placement.9,38 Patients with multivessel dissection, left main dissection or failed stent placement should be considered for coronary artery bypass grafting.12,14 A consensus on the optimal duration of medical therapy in patients with SCAD without atherosclerotic coronary artery disease remains to be established. Moreover, because of the association of SCAD with pregnancy, it is reasonable to recommend the patient wait before conception, although the appropriate duration is not known. Conclusion. To our knowledge, the first patient discussed here is the first reported case of RCA dissection in association with oral contraceptive use. Our second case highlights complicated PCI in a patient with spontaneous dissection. In young patients without traditional risk factors for coronary artery disease, a high index of suspicion is required to make the diagnosis of SCAD. Timely diagnosis and management are necessary prerequisites for a favorable outcome.
Author Affiliations: From the *Department of Medicine, Johns Hopkins University/Sinai Hospital, Baltimore, Maryland, and the §Division of Cardiology, Johns Hopkins Hospital. The authors report no conflicts of interest regarding the content herein. Manuscript submitted Address for correspondence: Lookman Lawal, MD, Department of Medicine, Johns Hopkins University/Sinai Hospital, 2401 W. Belvedere Avenue, Baltimore, MD 21215. E-mail: firstname.lastname@example.org
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