Spontaneous Coronary Artery Dissection and Severe Hypothyroidism

From the Division of Cardiology, Hospital of Saint Raphael, New Haven, Connecticut. The authors report no conflicts of interest regarding the content herein. Manuscript submitted November 20, 2008, and accepted December 3, 2008. Address for correspondence: Costin N. Ionescu, MD, PhD, Division of Cardiology, Hospital of Saint Raphael, 1450 Chapel Street, New Haven, CT 06511. E-mail: cionescu@srhs.org

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J INVASIVE CARDIOL 2009;21:E60-E62 Case Report. A 44-year-old female was admitted to an outlying hospital for substernal pressure radiating to her left shoulder and scapula associated with shortness of breath, nausea, vomiting and diaphoresis. The patient reported a 2-week history of right-sided neck and shoulder pain for which she had been using ibuprofen on a daily basis. The patient was treated with aspirin, clopidogrel, intravenous heparin and eptifibatide. Beta-blockers were withheld due to a heart rate of 56 bpm. The electrocardiogram (ECG) demonstrated sinus bradycardia at 54 bpm with nonspecific inferior T-wave abnormalities. Physical examination demonstrated no jugular venous distension, clear lungs, normal heart sounds and no peripheral edema. Laboratory studies were remarkable for the following: BUN of 17 mg/dl, creatinine of 1.9 mg/dl, CPK of 202 U/l, CPK-MB of 14 ng/ml, Troponin T of 0.06 ng/ml and LDL of 137 mg/dl. Her past medical history was notable for Graves’ disease diagnosed 20 years prior to admission and treated with radioactive iodine. The patient remained euthyroid until 2 years prior to admission when she was diagnosed with hypothyroidism and placed on thyroxine. She discontinued the thyroxine after 1 year of therapy for unclear reasons. A bilateral oophorectomy had been performed at age 34, and she had never been on hormone replacement therapy. She was actively smoking 1 pack of cigarettes per day. The patient was transferred to our hospital for emergent catheterization in the setting of non-ST-elevation myocardial infarction. Catheterization demonstrated a left ventricular end-diastolic pressure of 25 mmHg. Left ventriculography in the 30º RAO projection showed a focal area of apical akinesis with otherwise preserved left ventricular systolic function and an ejection fraction of 60%. Coronary angiography showed a right dominant circulation. There was a long tubular (50 mm) stenosis starting at the ostium of the left anterior descending artery (LAD) and extending into the mid-vessel (Figure 1). Intracoronary nitroglycerin had no effect on the degree of stenosis, but increased the distal reference vessel diameter. There were extensive fistulous connections from the left coronary artery to the left ventricular cavity. The circumflex artery (Cx) had mild luminal irregularities in the proximal vessel and the first obtuse marginal branch. The right coronary artery (RCA) was normal with less prominent fistulous communications from the distal posterolateral branches to the left ventricular cavity. Following catheterization, further laboratory data demonstrated a thyroid-stimulating hormone (TSH) of 41.86 µIU/ml (normal range: 0.27–4.20) and a free T4 of 0.16 ng/dl (normal range: 0.93–1.70). The stenosis in the LAD was thought to be unsuitable for percutaneous treatment due to the length and involvement of the ostium of the LAD, and the patient was referred for coronary artery bypass surgery (CABG). The surgery was delayed due to the azotemia, clopidogrel administration and concern regarding the newly diagnosed severe hypothyroidism. Approximately 2 days following catheterization, the patient experienced acute onset of severe chest discomfort. A repeat ECG showed new ST-segment elevation in leads I, AVL, V5 and V6, with ST-depression and T-wave inversion in leads II and III. An intra-aortic balloon pump was placed with improvement in her symptoms and she was sent for emergent CABG. A left internal mammary artery graft to the mid-LAD was placed without complications. When the patient was weaned from cardiopulmonary support, intraoperative transesophageal echocardiography demonstrated a new lateral wall-motion defect. Cardiopulmonary bypass was reinstituted and a saphenous vein graft was placed to the first diagonal and first obtuse marginal branches. The marginal branch was found to contain thrombus. Upon weaning from cardiopulmonary support the second time, the patient required intravenous pressor and inotropic support with dopamine. Repeat echocardiography showed apical akinesis and moderate-to-severe global hypokinesis. The following day, the patient developed recurrent malignant ventricular arrhythmias and resuscitation efforts were unsuccessful. An autopsy showed dissection of the left main coronary artery extending into the mid-LAD, the Cx and the obtuse marginal branch. There was an extensive hematoma in the dissection plane with compression of the native vessel lumina (Figures 2 and 3). Discussion. Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS). It was first described by Pretty in 1931,1 with only 152 cases reported by Kamineni et al on a literature review from 1952­–2002.2 The reported incidence varies from 0.1–1.1% of all ACS presentations.3 Based on case reports, the etiology can be classified into several groups: (a) trauma to the vessel: cardiac catheterization, coronary angioplasty, CABG and blunt chest trauma; (b) hormone-related: pregnancy, peripartum period or oral contraceptive use; (c) genetic defect: Marfan’s syndrome, Type IV Ehlers-Danlos syndrome, antitrypsine deficiency, cystic medial necrosis; (d) miscellaneous: intense physical activity, cocaine abuse or retrograde propagation from an aortic dissection. SCAD can present as any form of ACS including cardiogenic shock. In the past, diagnosis was generally made postmortem. With the improvement in diagnostic modalities the diagnosis of SCAD is now usually made by angiography. The classic angiographic description of dissection is of a radiolucent area within the lumen of the vessel. As in our patient, angiography may not show a flap, but instead, may appear as a long tubular lesion as a consequence of the true lumen being compressed by the false lumen, which may have blood flow or be occluded by thrombus. It is not known if different angiographic appearances coincide with different outcomes. Theoretically, the absence of a flap could be associated with worse prognosis since the true diagnosis may be missed with either inappropriate therapy or possible further extension of the dissection. De Maio et al found SCAD in three groups: (a) patients with atherosclerosis; (b) patients in the postpartum period; and (c) patients without an identifiable factor.4 The second group could be extended to include pregnancy,3 with SCAD causing up to one-third of MIs during pregnancy or the post-partum period. Reviews of the SCAD show a predominance in females, with the LAD more frequently involved. The RCA is usually the culprit vessel in males.2,3 Several hypotheses have been suggested to explain the pathophysiology of SCAD. Thayer et al proposed disruption of the vasa vasorum with intramedial hemorrhage with subsequent dissection.5 Rabinowitz et al postulated medial weakness secondary to accumulation of eosinophils and secretion of lytic enzymes.6 A copper deficiency was suggested by Asuncion et al,7 while a defect of collagen metabolism or cystic medial degeneration have also been proposed.8,9 In a review of 58 cases of SCAD associated with pregnancy, Koul et al found multivessel involvement in 40% of patients, supporting the hypothesis that the hormonal changes during pregnancy could account for the development of SCAD in pregnancy.10 Our patient led us to revisit the possible link between SCAD and hypothyroidism (Table 1). Review of published cases to identify the incidence of hypothyroidism in SCAD was difficult, because not all published case reports include a past medical history. The majority of cases reviewed focused only on cardiovascular risk factors. Prior publications have noted a correlation between vascular dissection and hypothyroidism. Rosenmann and Yarom reviewed autopsies of 106 cases of dissecting aortic aneurysm and compared them with a control group of 100 patients matched for age, sex, race, hypertension, severity of atherosclerosis and heart weight. Thyroid changes were found in 49/101 (49%) patients with aortic dissection, and in 18% in the control group (χ2 test, p = 0.00001). In 22% of the aortic dissection cases, notable changes in the thyroid that could cause clinical hypothyroidism were observed.11 In a prospective case-control study, 29 patients with cerebral infarct caused by spontaneous cervical artery dissection were compared with non-cervical artery dissection ischemic stroke.12 The diagnosis of autoimmune thyroiditis was based on positive serum titers of antithyroperoxidase, antithyroglobulin or both, and/or on the ultrasonographic pattern of diffuse or irregular hypoechogenicity of the thyroid. Antithyroid autoimmunity was present in 9/29 patients (31%) with cervical artery dissection and 2/29 patients (6.9%) with ischemic stroke. In a retrospective study, 48 hypothyroid patients who underwent percutaneous transluminal coronary angioplasty (PTCA) were compared to 122 euthyroid patients who had PTCA over the same period (1984–1994).21 Coronary dissection occurred more frequently in patients with hypothyroidism compared to the euthyroid patients (24/48 vs. 41/122; p = 0.06). Of the 4 patients with overt hypothyroidism, 2 developed dissection post procedure. We could find no reports of specific changes involving the coronary arteries in hypothyroidism. We can only speculate that the changes reported in edematous tissue in hypothyroidism13 or in fibroblast culture14 of increased hyaluronic acid may also apply to the wall of the coronary arteries. In addition, recent data implicate the accumulation of hyaluronic acid in the initial steps of plaque erosion, acting as a principal player in the development of thrombosis.15 Together, these would suggest a possible link between hypothyroidism and coronary artery dissection with thrombus formation at the interface between the media and adventitia. In conclusion, although a clear correlation between hypothyroidism and coronary artery dissection cannot be drawn, we suggest that in patients with hypothyroidism presenting with an unstable coronary syndrome, SCAD should be considered in the differential diagnosis, or if the diagnosis of SCAD is established, the TSH should be measured to assess the thyroid function.

1. Pretty HC. Dissecting aneurysm of coronary artery in a woman aged 42: Rupture. BMJ 1931;1:667.
2. Kamineni R, Sadhu A, Alpert JS. Spontaneous coronary artery dissection: Report of two cases and a 50-year review of the literature. Cardiol Rev 2002;10:279–284.
3. Maeder M, Ammann P, Angehrn W, Rickli H. Idiopathic spontaneous coronary artery dissection: Incidence, diagnosis and treatment. Int J Cardiol 2005;101:363–369.
4. DeMaio SJ Jr, Kinsella SH, Silverman ME. Clinical course and long-term prognosis of spontaneous coronary artery dissection. Am J Cardiol 1989;64:471–474.
5. Thayer JO, Healy RW, Maggs PR. Spontaneous coronary artery dissection. Ann Thorac Surg 1987;44:97–102.
6. Robinowitz M, Virmani R, McAllister HA Jr. Spontaneous coronary artery dissection and eosinophilic inflammation: A cause and effect relationship? Am J Med 1982;72:923–928.
7. Asuncion CM, Hyun J. Dissecting intramural hematoma of the coronary artery in pregnancy and the puerperium. Obstet Gynecol 1972;40:202–210.
8. Bonnet J, Aumailley M, Thomas D, et al. Spontaneous coronary artery dissection: case report and evidence for a defect in collagen metabolism. Eur Heart J 1986;7:904–909.
9. Adkins GF, Steele RH. Left coronary artery dissection: an unusual presentation. Br Heart J. 1986;55:411–414.
10. Koul AK, Hollander G, Moskovits N, et al. Coronary artery dissection during pregnancy and the postpartum period: Two case reports and review of literature. Catheter Cardiovasc Interv 2001;52:88–94.
11. Rosenmann E, Yarom R. Dissecting aneurysm of the aorta and hypothyroidism. Isr J Med Sci 1994;30:510–513.
12. Pezzini A, Del Zotto E, Mazziotti G, et al. Thyroid autoimmunity and spontaneous cervical artery dissection. Stroke 2006;37:2375–2377.
13. Parving HH, Helin G, Garbarsch C, et al. Acid glycosaminoglycans in myxoedema. Clin Endocrinol 1982;16:207–210.
14. Shishiba Y, Yanagishita M, Hascall VC. Effect of thyroid hormone deficiency on proteoglycan synthesis by human skin fibroblast cultures. Connect Tissue Res 1988;17:119–135.
15. Kolodgie FD, Burke AP, Farb A, et al. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: Insights into plaque erosion. Arterioscler Thromb Vasc Biol 2002;22:1642–1648.
16. Rovner A, Thanigaraj S, Rogers JG, et al. Spontaneous multivessel coronary artery dissection in a young asymptomatic patient. J Interv Cardiol 2004;17:123–127.
17. McDonald GS. Spontaneous primary dissection of the coronary artery. Ir J Med Sci 1989;158:304–306.
18. Thompson EA, Ferraris S, Gress T, Ferraris V. Gender differences and predictors of mortality in spontaneous coronary artery dissection: A review of reported cases. J Invasive Cardiol 2005;17:59–61.
19. Narasimhan S. Spontaneous coronary artery dissection (SCAD). IJTCVS 2004;20:189-191.
20. Okamoto R, Makino K, Saito K, et al. Aorto-coronary dissection during angioplasty in a patient with myxedema. Jpn Circ J 2000;64:316–320.
21. Mantzoros CS, Evagelopoulou K, Moses AC. Outcome of percutaneous transluminal coronary angioplasty in patients with subclinical hypothyroidism. Thyroid 1995;5:383–387.