Congenital Ostial Left Main Coronary Artery Stenosis Associated with a Bicuspid Aortic Valve in a Young Woman

An ostial left main coronary artery (LMCA) stenosis is usually associated with underlying atherosclerotic disease. Uncommon nonatherosclerosis causes include congenital anomalies such as congenital atresia and hypoplasia of the LMCA, which are associated with sudden cardiac death. These abnormalities have been described in infants and children,^1,2 but have rarely been reported among adults.^3,4 Other conditions that may involve the ostium of the LMCA include Takayasu aortitis,⁵ syphilitic aortitis,⁶ and radiation-induced coronary artery stenosis.⁷ We report the first case of an intravascular ultrasound (IVUS) documented congenital LMCA stenosis associated with a bicuspid aortic valve in a young woman who did not have any other known conditions that would have involved the ostium of the LMCA. Case Report. A 41-year-old woman with no history of smoking or known cardiac risk factors presented with typical exertional angina. The patient underwent stress echocardiography, and after two minutes of exercise, she developed chest pain associated with 2 mm ST-segment depression in the inferolateral leads. The stress echocardiography also demonstrated significant anteroapical and septal wall motion abnormalities during exercise. The patient was then referred for coronary angiography. The angiogram demonstrated that the right coronary artery was angiographically normal, nondominant, and arose from the right sinus of Valsalva. However, the LMCA was difficult to engage due to a high take-off and a narrow aortic root. The left coronary angiography was performed by the subselective engagement of a 6 Fr left coronary Judkins catheter and then by a 6 Fr multipurpose catheter, which demonstrated an ambiguous LMCA stenosis. In order to determine the significance of the LMCA stenosis, the LMCA was engaged with a 6 Fr extra-backup curve guiding catheter, which resulted in mild dampening of the pressure waveform without hemodynamic instability. After intracoronary nitroglycerin injection, the coronary angiogram revealed an ambiguous ostial LMCA stenosis with no stenosis in the other coronary arteries (Figure 1). Subsequently, IVUS was performed using an Atlantis™ SR Pro catheter (Boston Scientific Corp., Natick, Massachusetts) with automated pullback at a rate of 0.5 mm/second. The IVUS images demonstrated a slit-like orifice of the LMCA, with a minimum lumen diameter (MLD) of 2.5 mm and a minimum lumen area (MLA) of 7.7 mm². The MLD and MLA at the distal LMCA were 4.1 mm and 17.2 mm², respectively (Figure 1). In addition, during the automated pullback from the left anterior descending (LAD) coronary artery to the aorta, no evidence of atheroma was noted in the LMCA (Figure 1). There was no history of the use of illicit drugs, diabetes mellitus, asthma, hypertension or hyperlipoproteinemia. Laboratory studies for collagen vascular diseases, hypercoagulability and syphilis were negative. In order to exclude anatomic causes of the narrowed LMCA ostium, transesophageal echocardiography (TEE) was performed, which demonstrated a bicuspid aortic valve with mild-aortic insufficiency and normal left ventricular function (Figure 2). In addition, on TEE, the ostial LMCA was stenotic and there was a turbulence of blood flow at the ostium of the LMCA (Figure 3). Since both the IVUS and stress test confirmed the presence of a significant LMCA stenosis, two-vessel coronary artery bypass grafting (CABG) was performed, and the patient has remained clinically stable. Discussion The patient we described was suffering from a hemodynamically significant nonatherosclerotic obstructive LMCA stenosis, as evidenced by her clinical symptoms, an abnormal stress test and abnormal IVUS parameters. The etiology of the ostial LMCA stenosis in the present case appears to be related to the congenital hypoplasia, because IVUS demonstrated that both the MLD and MLA at the ostium of the LMCA were significantly smaller compared with distal LMCA, and there was no evidence of atheroma in the LMCA. Obstructive coronary anomalies have not previously been reported in association with a bicuspid aortic valve. Among patients with a bicuspid aortic valve, Johnson et al.⁸ described a number of angiographic variations of the left coronary artery in a series of 33 patients. They reported that compared with the control group, patients with a bicuspid aortic valve have a higher incidence of immediate bifurcation of the LMCA, the length of the LMCA 9 reported that among patients with a significant LMCA stenosis, medical therapy alone was associated with a 3-year survival rate of 41%. Given the patient’s low operative risk, the presence of normal ejection fraction and the absence of other epicardial coronary artery disease, we felt that coronary artery bypass grafting would be the procedure of choice for definitive treatment of her symptoms. An alternative surgical technique might have included endarterectomy of the LMCA, with closure of the incision using either a pericardial or venous patch.¹⁰ Although stenting of the unprotected LMCA stenosis has been associated with a high technical success rate and a low procedure risk, the long-term follow up data demonstrated a high rate of angiographic restenosis, with a relatively high incidence of cardiac death.¹¹ In a small study,¹² the use of sirolimus-eluting stents in patients with an unprotected LMCA stenosis was associated with a favorable outcome; however, the long-term effect of such a therapy will need to be corroborated in a larger study. An isolated ostial LMCA stenosis is a rare condition. Among 21,545 adult patients who underwent consecutive coronary angiography, Topaz et al.¹³ reported 12 patients (0.06%) with an isolated ostial LMCA stenosis, 10 of whom had at least one major cardiac risk factor; the most common presentation was unstable angina and their left ventricular ejection fraction was normal. Similarly, Miller et al.¹⁴ described 5 of 4,000 patients (0.001%) who had an isolated LMCA stenosis. All 5 were middle-aged women who underwent CABG, and 2 patients were found to have atherosclerotic disease at the time of surgery. Likewise, Thompson et al.¹⁵ reported the coronary angiograms of 5 young women (ages 31–48 years) of 2,105 consecutive angiograms (0.02%) who had an isolated LMCA stenosis. Of these, 3 patients had at least one major cardiac risk factor and a histopathological study was obtained only in 1 case, which demonstrated typical atheroma. The incidence of atherosclerosis as an etiology of an isolated LMCA stenosis among young women is unknown because in the majority of the aforementioned cases, histopathological information or IVUS examination is not available. In a number of studies,^16,17 early atherosclerosis, especially among women, has been implicated. In a case report of a 34-year-old woman, the autopsy examination demonstrated intimal fibrosis as the etiology of severe LMCA stenosis.¹⁸ In another report,¹⁹ the autopsy examination of the LMCA in a 35-year-old woman who died during cardiac catherization demonstrated congenital stenosis of the LMCA by a myointimal flap that was bridging the ostium. Similarly, the autopsy study of a 60-year-old man who died suddenly demonstrated congenital atresia of the LMCA.³ Other nonatherosclerotic causes of the LMCA stenoses include Takayasu’s aortitis,⁵ syphilitic aortitis and radiation-induced LMCA stenosis.⁷ Another uncommon anatomic cause of the LMCA stenosis is the presence of a nonatherosclerotic membrane projecting from the wall of the aorta into the coronary ostium, resulting in a slit-like orifice and obstruction.¹⁹ The anatomic origins of the coronary ostium may also pose hemodynamic consequences. It is worth noting that the ostium of the left coronary artery is normally located within the sinus of Valsalva, which facilitates coronary perfusion in diastole. If an ostium is located in the tubular portion of the ascending aorta (i.e., high take-off), there may be a higher risk of angina and sudden cardiac death due to acute take-off of the LMCA and decreased coronary blood flow.²⁰ It should be noted, however, that the angiographic assessment of a LMCA stenosis is often difficult and unreliable.²¹ Furthermore, autopsy studies have demonstrated that in many situations in which the LMCA was mildly diseased, they were often reported by angiography as significantly stenosed.²² Patients with only mild-to-moderate LMCA stenosis have a low event rate, and an operation performed too early may lead to the premature closure of either native vessels or the grafts.²³ IVUS is an invaluable tool to assess the significance of the LMCA stenosis. However, IVUS was not performed in any of the aforementioned studies. IVUS parameters for delineating hemodynamically significant LMCA stenosis have recently been validated by Jasti et al.,²⁴ who reported that an IVUS MLD and MLA of 2.8 mm and 5.9 mm², respectively, strongly predicted an FFR cut-point of 0.75. In addition, these investigators²⁴ reported that among patients with a LMCA stenosis, an FFR cut-point of 0.75 is a strong predictor of survival and event-free survival rates. Though in the current case, the MLA by IVUS was 7.7 mm², which was greater than the MLA cut-off value of 5.9 mm² for the significance of the LMCA stenosis, the MLD by IVUS was 2.5 mm, and that was smaller than the MLD cut-point of 2.8 mm for the significance of the LMCA stenosis. In this context, Jasti et al.²⁴ have shown that an MLD cut-point of 2.8 mm has the highest sensitivity and specificity for determining the significance of the LMCA stenosis, followed by an MLA cut-point of 5.9 mm². Likewise, Bech et al.,²⁵ in a study of 54 patients with a LMCA stenosis, demonstrated that regardless of the angiographic severity of the LMCA stenosis, a fractional flow reserve (FFR) > 0.75 is associated with excellent long-term outcomes. Conclusion In conclusion, the congenital ostial LMCA stenosis, though an uncommon entity, is not confined to childhood and should be kept in mind as a potential cause of angina, especially among young women who have no cardiac risk factors and present with angina. The significance of an isolated ostial LMCA stenosis is difficult to determine by angiography alone, and IVUS will provide valuable information with respect to etiology and a decision-making strategy such as revascularization or medical therapy. Specifically, with the advent of recent IVUS cut-off values validated by FFR,²⁴ the significance of the LMCA stenosis can readily be determined during a short automated pullback from the ostium of the LAD to the aorta.

1. Byrum CJ, Blackman MS, Schneider B, et al. Congenital atresia of the left coronary ostium and hypoplasia of the left main coronary artery. Am Heart J 1980;99:354–358. 2. Mullins CE, El Said G, McNamara DG, et al. Atresia of the left coronary artery ostium. Circulation 1972;46:989–994. 3. Fortuin NJ, Roberts WC. Congenital atresia of the left main coronary artery. Am J Med 1971;50:385–389. 4. Lobo FV, Cairns JA, Stolberg HO, Heggtveit A. Death following coronary angiography in a young woman with isolated left coronary ostial stenosis. Can J Cardiol 1989;5:149–154. 5. Chun MPKC, Jones CR, Robinowitz M, et al. Coronary ostial stenosis in Takayasu’s aortitis. Chest 1980;78:330–331. 6. Yamada T, Sakamoto T, Asano K. Surgical treatment of syphilitic coronary ostial stenosis with aortic regurgitation. J Cardiovasc Surg 1983;24:222–226. 7. Chinnasami BR, Schwartz RC, Pink SB, Skotnicki RA. Isolated left main coronary stenosis and mediastinal irradiation. Clin Cardiol 1992;15:459–461. 8. Johnson AD, Detwiler JH, Higgins CB. Left coronary artery anatomy in patients with bicuspid aortic valves. Br Heart J 1978;40:489–493. 9. Coneley MJ, Ely RL, Kisslo J. The prognostic significance of left main stenosis. Circulation 1978;64:947–952. 10. Sabiston DC, Ebert PA, Friesinger GC, et al. Proximal endarterectomy, arterial reconstruction for coronary occlusion at aortic origin. Arch Surg 1965;91:758–764. 11. Takagi T, Stankovic G, Finci L, et al. Results and long-term predictors of adverse clinical events after elective percutaneous interventions on unprotected left main coronary artery. Circulation 2002;106:698–702. 12. Arampatzis CA, Lemos PA, Tanabe K, et al. Effectiveness of sirolimus-eluting stent for treatment of left main coronary artery disease. Am J Cardiol 2003;92:327–329. 13. Topaz O, Warner M, Lanter P, et al. Isolated significant left main coronary artery stenosis: Angiographic, hemodynamic, and clinical findings in 16 patients. Am Heart J 1991;122:1308–1314. 14. Miller GAH, Honey M, El-Sayed H. Isolated coronary ostial stenosis. Cathet Cardiovasc Diagn 1986;12:30–34. 15. Thompson R. Isolated coronary ostial stenosis in women. J Am Coll Cardiol 1986;7:997–1003. 16. Pritchard CL, Mudd JG, Barmer HB. Coronary ostial stenosis. Circulation 1975;52:46–48. 17. Cohen MV, Cohen PF, Herman MV, Gorlin R. Diagnosis and prognosis of main coronary obstruction. Circualtion 1972;45:57–62. 18. Afksendiyos K. Left coronary ostial stenosis caused by focal intimal fibrosis. Ann Intern Med 1999;131:717–719. 19. Josa M, Danielson GK, Wiedman WH, Edwards WD. Congenital ostial membrane of the left main coronary artery ostium. Br Heart J 1982;48:298–300. 20. Virmani R, Chun PK, Goldstein RE, et al. Acute take-offs of the coronary arteries along the aortic wall and congenital coronary ostial valve-like ridges: Association with sudden cardiac death. J Am Coll Cardiol 1984;3:766–771. 21. Cameron A, Kemp HG Jr, Fisher LD, et al. Left main coronary artery stenosis: Angiographic determination. Circulation 1983;68:484–489. 22. Arnett EN, Isner JM, Redwood DR, et al. Coronary artery narrowing in coronary heart disease: Comparison of cineangiographic and necropsy findings. Ann Intern Med 1979;91:350–356. 23. Abizad AS, Mintz GS, Abizad A, et al. One-year follow up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms. J Am Coll Cardiol 1999;34:707–715. 24. Jasti V, Ivan E, Yalamanchili V, et al. Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis. Circulation 2004;110:2831–2836. 25. Bech GJ, Droste H, Pijls NH, et al. Value of fractional flow reserve in making decisions about bypass surgery for equivocal left main coronary artery disease. Heart 2001;86:547–552.