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Coronary artery aneurysm: A review
Coronary Artery Aneurysm: A Review Mushabbar
Syed and Michael
Lesch
Coronary artery aneurysm is defined as coronary dilatation which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. This is an uncommon disease which has been diagnosed with increasing frequency since the advent of coronary angiography. The incidence varies from 1.5% to 5% with male dominance and a predilection for the right coronary artery. Atherosclerosis accounts for 50% of coronary aneurysms in adults. Reported complications include thrombosis and distal embolization, rupture and vasospasm. The natural history and prognosis remains obscure. Controversies persist regarding the use of surgical or medical management. The authors recommend surgery based on the severity of associated coronary stenosis rather than the mere presence of aneurysm. Medical therapy is indicated for the majority of patients and consists of antiplatelet and anticoagulant medication. Copyright © 1997 by W.B. Saunders Company
oronary artery aneurysm is an uncommon disease, which has been diagnosed with increasing frequency since the advent of coronary angiography. The first case of coronary artery aneurysm was reported by Morgagni in 1761.1 In 1958 Munker et al 2 reported the first antemortem case of coronary aneurysm diagnosed by coronary angiography. The natural history and prognosis of coronary aneurysms remains obscure. Management of these patients remains a therapeutic dilemma with published recommendations based on anecdotal experience. In an attempt to collate presently available data, a review of the literature regarding pathophysiology, management, and prognosis of this disease is presented herein.
C
Definition Aneurysmal coronary artery disease is defined as coronary dilatation which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. 3,4
Markis et al 5 used the term "ectasia" to describe coronary aneurysmal dilatation and attempted to further classify it on the basis of appearance and the number of coronary arteries involved in coronary angiography. They described type 1 as diffuse ectasia of all three major vessels, type 2 as diffuse ectasia in one vessel and localized disease in one other major vessel, and type 3 as diffuse ectasia in one vessel only. Tunick et al6 also classified aneurysms as discrete or localized abnormal dilatation of the coronary artery that is spherical or saccular. They excluded fusiform aneurysms and called them "ectasia." The authors propose that the term aneurysm be restricted to a localized, abnormal dilatation of coronary arteries which can be saccular or fusiform in shape, reserving the term ectasia to describe diffuse dilatation only. Diffuse dilatation involves the majority of the length of the artery (at least 50%). Using the term aneurysm and ectasia to define specific anatomic substrates should help to standardize the reporting of this disease and minimize discrepancies in the literature regarding management.
Incidence and Anatomic Distribution A literature search for large studies reporting the incidence and anatomic distribution of coronary artery aneurysm is summarized in Table 1. The incidence of coronary aneurysms varies from 1.5% to 5% which may be related to different criteria used to define aneurysms as previously discussed. In a postmortem study of 694 patients, Daoud et al 7 found a 1.4% incidence of coronary aneurysms. The largest antemortem series of From the Department of Internal Medicine, Division of Cardiology, Henry Ford Hospital, Detroit, MI. Address reprint requests to Michael Lesch, MD, FACC, Chairman Department of Internal Medicine, K-2, Henry Ford Hospital, Detroit, M148202. Copyright © 1997 by W.B. Saunders Company 0033-0620/97/4001-000755.00/0
Progress in Cardiovascular Diseases, Vol. 40, No. 1 (July/August), 1997: pp 77-84
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TABLE 1. Coronary Artery Aneurysms, Incidence, and Anatomic Site Authors
No. of Patients
No. of Patients With Aneurysms (%)
Markis et al5 Tunick et al6 Daoud et al7 Rath et aP° Berkoff et a119 Befeler et al2° Swanton et a147 Aintablian et a155 Hartnell et a157 Falsetti et a158 Oliveros et a159
20,087 2,457 8,422 694 1,100 1,342 1,246 1,000 1,660 4,993 742 1,500
978 (4.9) 30 (1.2) 20 (0.2) 10 (1.4) 5 (0.5) 5 (0.3) 16 (1.3) 12 (1.2) 42 (2.5) 70 (1.4) 11 (1.5) 5 (0.3)
Pooled data
45,243
1,204 (2.6%)
CASS 3'4
Number of Coronary Aneurysms RCA
LAD
LCX
LM
1,122 NR 2 8 3 0 13 6 34 52 9 4
440 NR 15 2 5 4 5 1 16 41 7 4
642 NR 4 2 3 1 8 6 14 34 10 3
35 NR 1 0 0 0 0 0 0 10 0 0
1,253 (40.4%)
1,002 (32.3%)
727 (23.4%)
46 (3.5%)
Abbreviations: NR, not reported; RCA, right coronary artery; LAD, left anterior descending artery; LCX, left circumflex; LM, left main coronary artery.
coronary aneurysms is reported by the Coronary Artery Surgery Study (CASS) registry. 3,4 This registry found an incidence of 4.9% diagnosed by coronary angiography. This is higher than other angiographic studies of coronary aneurysms reporting an incidence of 0.37% to 2.53% (Table 1). The right coronary artery seems to be the most commonly involved followed by the left anterior descending artery. Left main involvement is very rare. s,9 Although coronary aneurysms are seen at any age, those related to atherosclerosis usually appear later in life than those of a congenital or inflammatory nature. 7 Atherosclerotic or inflammatory coronary aneurysms are usually multiple and involve more than one coronary artery as compared with congenital, traumatic, or dissecting aneurysms which are mainly single. 1° Males are more commonly affected. In CASS, 3 the number of males with coronary aneurysms was significantly more than the control group (88.2% v 80.1%, P < .001).
Etiology The different etiologies which have been postulated for coronary artery aneurysms are summarized in Table 2. The most common etiology is atherosclerosis accounting for 50% of coronary aneurysms diagnosed in adults. This is followed by Kawasaki's disease and congenital aneurysms. In a review of the literature on postmortem aneurysms, Daoud et al 7 found 52% were caused
by atherosclerosis, 17% were congenital, 11% each were mycotic-embolic and dissecting, and 4% were leutic. Kawasaki's disease causing coronary artery aneurysm as a late sequelae is probably more common than congenital aneurysms especially in areas of higher prevalence, ie, Japan. 1° More recently, coronary artery aneurysms have been described as a consequence of coronary angioplasty. This was first reported by Holmes et a111 following balloon angioplasty (PTCA). Walford et al t2 reported an incidence of 0.3% in a group of 240 patients following PTCA, most of whom had dissection at the time of initial procedure. In another study, Bal et aP 3 followed 728 patients after successful PTCA and repeated angiography after a mean of 4.5 months. A coronary aneurysm at the site of PTCA was found in 3.9% of patients. In the group who had PTCA compli-
TABLE 2. Etiology of Coronary Artery Aneurysm Atherosclerosis Kawasaki disease Congenital Coronary angioplasty (balloon, laser, atherectomy) Arteritis (polyarteritis nodosa, syphilis, SLE, Takayasu's)
Mycotic Dissection Trauma Connective tissue disorders (Marfan's and Ehlers-Danlos syndromes) Metastatic tumor
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cated by dissection, the incidence of coronary aneurysms was 9% as compared with 2.9% in patients who did not have dissection complicating PTCA. Use of an oversized balloon has been proposed as a predisposing factor.14 Early and late development of coronary aneurysms following directional atherectomy (DCA) has also been well described. 15,j6 Early coronary aneurysms after DCA is related to coronary perforation leading to "pseudoaneurysm" formation, whereas late coronary aneurysms after DCA are attributed to subintimal damage. 15 A recently reported multicenter study comparing acute complications of Excimer Laser Coronary Angioplasty t7 found a 0.3% incidence of coronary aneurysm after the procedure. This rare complication has been reported with both, Ho-YAG and Excimer lasers.18
aneurysm is an abnormal vessel media which may be secondary to an extension of the intimal arteriosclerotic process. More recently, nitric oxide (NO) has been implicated in the formation of aneurysms. 21 NO stimulates the relaxation of vascular smooth muscle via the guanylate cyclase pathway and release of calcium from the endoplasmic reticulum. One possibility is that there is an imbalance between the beneficial effects of NO on coronary dilation and the potentially detrimental effects of chronic overstimulation by this endothelium derived relaxation factor. Extended exposure to herbicides causing increased production of acetylcholine22 and chronic exposure to nitrites in munitions workers 23 has been proposed to potentially stimulate NO leading to the formation of coronary aneurysms. 2~
Pathogenesis
Clinical Features
There is consensus that the majority (50%-52%) of coronary artery aneurysms are arteriosclerotic in origin. Microscopic examination reveals the usual findings of arteriosclerosis, ie, hyalinization and lipid deposition of the intima, destruction of the intima and media, focal calcification and fibrosis, cholesterol crystals, intramural hemorrhages, and foreign body giant cell reaction of the arteriosclerotic process. 5,7 Daoud et al 7 suggested the pathogenesis of aneurysms to be consequent to a poststenotic transformation of kinetic energy to potential energy or lateral pressure. However, coronary aneurysms occur in the absence of proximal stenosis. Berkoff and Rowe ~9postulated the presence of a thin, degenerated media adjacent to an intimal plaque as the primary pathological requirement leading to plaque rupture and erosion of the grumous material by the blood stream. This excavated plaque then becomes the site of aneurysm formation. Befeler et al 2° also speculated the presence of an intrinsically abnormal vessel media and an intimal injury on or about a plaque with resulting ulceration and hemorrhage giving rise to dilatation and aneurysm formation. Another theory put forward by Markis et al 5 suggests the possible cause as the intraluminal pressures against an elastic vessel wall with decreased stress tolerance due to destruction of the media. All these authors agree that the essential component in the formation of coronary
There are no clinical features characteristic of coronary artery aneurysms. Symptoms of angina or myocardial infarction are of the usual presentation. Occasionally a systolic murmur is heard over the precordium. Association with abdominal aortic aneurysm 7,2° and hypertension 5,19,2° has been postulated. Swaye et aP did not find significant differences in risk factors, subjective symptoms, or left ventricular function among patients with or without coronary aneurysms enrolled in the CASS registry. A history of Kawasaki's disease or connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome) may be helpful in suggesting the diagnosis. The possibility of coronary artery aneurysm should be considered in young patients with ischemic chest pain.
Diagnosis The diagnosis of Coronary artery aneurysm in a patient with suspected myocardial ischemia is made on the basis of cardiac imaging procedures. Coronary angiography is the gold standard in the diagnosis of coronary aneurysm and not only provides information regarding the size, shape, location, and number of aneurysms, but also delineates the presence or absence of associated stenosis. Some noninvasive methods have limited ability to define the presence of coronary aneurysm. Echocardiography, both two-dimensional
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transthoracic (2-DE) and transesophageal (TEE), have been used in the diagnosis of coronary aneurysms. 24,2s As proximal right and left coronary arteries are better visualized by TEE, this technique may have greater sensitivity. 2-DE is the primary mean of screening for coronary aneurysms in children with Kawasaki's disease. In a study of 70 patients with Kawasaki's disease, Capanneri et al, 26 found the sensitivity of 2-DE was 100% in detecting proximal coronary aneurysm, suggesting its usefulness in selecting patients for invasive coronary angiography. Coronary artery aneurysms in children have also been detected by computed tomography scanning 27,2B and magnetic resonance (MR) imaging. 29 Pucillo et aP ° described the usefulness of MR imaging in establishing the size and position in an adult patient. Jumbo Ge et al, 31 recently reported that intravascular ultrasound deployment leads to better aneurysm characterization as compared with coronary angiography and helps in differentiating between true and false aneurysms.
Kawasaki Disease Kawasaki disease or mucocutaneous lymph node syndrome deserves special mention because it is the most common cause of coronary aneurysm in children and the second most common in adults after atherosclerosis. Kawasaki disease is a systemic vasculitis syndrome which involves the medium and small size arteries, particularly coronary arteries. This syndrome was first described by Kawasaki in Japan in 1967, and is primarily a disease of childhood usually affecting children under the age of 5 years. The principal features are described as (1) fever persisting for 5 days or more, (2) skin changes with reddening of palms and soles in the early stages with subsequent membranous desquamation from finger tips in the convalescent stage, (3) polymorphous exanthema, (4) bilateral conjunctival congestion, (5) changes of the lips and oral cavity--reddening of the lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa, and (6) acute nonpurulent cervical lymphadenopathy. Although the disease is generally self-limited, 15% to 25% of children may develop coronary aneurysms 32,33 which may develop any time after day 7. Other cardiovascular lesions include myocarditis, pericarditis, and valvular involvement. Risk factors
that predict the presence of coronary aneurysms include (1) boys under 1 year of age, (2) fever lasting longer than 2 weeks, (3) elevated sedimentation rate persisting for more than 4 weeks, and (4) palpable axillary artery aneurysms. 34 Aspirin (100 mg/kg/d through day 14 of the illness and then 3-5 mg/kg/d) has been the mainstay of treatment but more recently high dose IV gamma globulin (400 mg/kg as a single dose) has been shown to reduce the development of coronary aneurysms if given early in the course of the disease. 35 One of the most exciting findings regarding coronary aneurysms in Kawasaki disease has been the occasional dramatic spontaneous regression of aneurysms in these children. In a series of 594 patients with coronary aneurysms due to Kawasaki disease reported by Kato, 36 55% of the small or moderate-sized aneurysms fully regressed Within 2 years of follow-up. Factors associated with regression include (1) age less than 1 year, (2) saccular as opposed to fusiform morphology, and (3) distal location. 37 Regression was unlikely in giant aneurysms or more than several years after onset. 36 The majority of deaths due to this illness are attributed to myocardial infarction within 6 months of symptom onset, but late presentation with acute coronary syndromes in adulthood has been well described in the literature. 38-42
Complications The natural history of coronary artery aneurysms is largely unknown. Most of the reports in the literature include small numbers of patients with short-term follow-up. C A S S 3,4 w a s the largest study of patients with coronary aneurysms but was biased towards a surgical intervention. Current recommendations are, therefore, based on anecdotal experience. Previous reports on the complications and outcomes of coronary aneurysms have reported the presence of thrombosis and distal embolization, rupture, and spasm.
Thrombosis and Distal Embolization Several case reports have described the presence of a thrombus inside the aneurysm. Daoud et al 7 in their postmortem study of 10 patients, found a thrombus inside the aneurysm in seven (70%). van den Broek and SegaP 3 described an interest-
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CORONARY ARTERYANEURYSM
ing case of a 19-year-old girl diagnosed with saccular aneurysms of the left anterior descending artery and its two diagonal branches on coronary angiography. Thrombus was seen in some of these aneurysms without any obstructing lesion being identified. The patient went on to develop anteroseptal myocardial infarction and a repeat cardiac catheterization showed occlusion proximal to the sites of aneurysms. Myler et a144 also described a case of coronary aneurysm associated with extensive thrombus formation seen at coronary arteriography. R a t h e t al 1° reported a coronary angiographic study of five patients with documented coronary artery aneurysms but no stenosis. These patients underwent repeat cardiac catheterization for recurrent angina and all five had total occlusions and infarcts in the territory of the vessel with the known aneurysm. Similar observations were reported by Anabtawi et a145 and Ebert et al, 46 who found thrombus inside the coronary artery aneurysm during bypass surgery. Befeler et al 2° described a series of six cases that had segmental left ventricular dysfunction in the territory of vessels with aneurysm but without significant obstruction. The authors state that a possible explanation can be distal embolization of material originating in the coronary aneurysm. Berkoff and Rowe 19 also described severe wall motion abnormalities in patients with coronary aneurysm (6 out of 15) supporting the possibility of distal embolization of the thrombus. Abnormal blood flow patterns inside an aneurysm have been associated with thrombus formation.I°,19 Swanton et a147 measured coronary sinus blood flow in 14 patients with ectatic coronary arteries and compared it with coronary sinus blood flow in 14 patients with nonectatic coronary arteries. This limited data set suggests the presence of reduced blood flow velocity in ectatic coronary arteries favoring the formation of thrombus. Despite several authors reporting the presence of thrombus and distal embolization in coronary aneurysms, the exact incidence of this complication is unknown. In addition it is also not clear if this complication occurs more frequently in certain types of aneurysms. 48
Rupture of CoronaryAneurysms Rupture of a coronary aneurysm leading to sudden death has been a concern which led some
authors to suggest surgery to avoid this complication. 45 Daoud et al 7 reported a 12% incidence of rupture in their review of 57 cases up to 1963. Several other authors have reported rupture of coronary aneurysms. 49'5° All these reports were autopsy reviews and hence biased towards this complication as an end event. In the largest reported cohort of coronary aneurysms (CASS), Swaye et aP did not find any case of rupture in 978 patients. In a recent review, Burns et al 4s commented that since the advent of angiography and the premorten diagnosis of coronary aneurysms, no case of rupture has been documented. This led the authors to conclude that despite the theoretical risk of rupture of coronary aneurysm, this outcome seems extremely rare and unpredictable.
Vasospasm As coronary artery aneurysms originate from an abnormal vessel media, it was believed they do not have enough intact smooth muscle to generate significant vasoconstriction. Hence, coronary aneurysms were typically absent from the large series of coronary vasospasm. 51,52 Bove et aP 3 described the first two cases of vasospasm at the site of coronary aneurysm. These patients underwent coronary arteriography for recurrent chest pain, which revealed diffuse aneurysmal dilatation of the coronary arteries without substantial narrowing. Administration of intravenous ergonovine maleate led to profound generalized constriction of ectatic arteries associated with ischemic chest pain. This was promptly reversed by nitroglycerine. In another case report, Gutowski et aP 4 described spasm of the coronary artery aneurysm in response to angioplasty; the stimulus appeared to be mechanical rather than neurohormonal. These data illustrate that aneurysms of coronary arteries are capable of vasoconstriction despite a weakened and thinned media, and may have a role in the etiology of downstream ischemia.
Treatment and Prognosis The appropriate therapy for patients with coronary artery aneurysms is unknown. Controversies persist regarding the use of surgical or medical management. Published guidelines have been based on anecdotal experience rather than controlled trials. This is in part related to the rare
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nature of this disease making it difficult to conduct such a trial. Surgery has been recommended for all but minor aneurysms in view of the risk for thrombosis and rupture especially in the presence of saccular aneurysms. 45,46,56 However, there are no data available comparing medical management with surgical intervention. For atherosclerotic aneurysms, most authors agree that surgical treatment is warranted depending on the severity of associated coronary stenosis rather than the mere presence of aneurysm. Aintablian et aP 5 did not find any short-term survival difference in patients with coronary aneurysm who had bypass surgery when compared with controls. This finding was confirmed by CASS, 3 showing no survival difference in medically treated patients with coronary aneurysm and either no or nonsignificant coronary artery stenosis (<70%) as compared with controls without coronary aneurysm or significant coronary disease. Surgery when indicated, consists of coronary artery bypass with or without aneurysm ligation or excision. Outcome was excellent when the aneurysm was not included in the anastomosis. 46,56 Medical therapy is indicated for the majority of patients in whom coronary stenosis is not sufficiently significant to warrant surgery and consists of antiplatelet and anticoagulant medication. Use of anticoagulation is based on the observations of thrombus formation in association with coronary artery aneurysms and its distal embolization as previously discussed. The limited data regarding the presence of vasospasm in coronary arteries with aneurysms may constitute an indication for the addition of a vasodilator, ie, nitrates or calcium channel blockers in the management of these patients. There is consensus that late coronary aneurysms due to PTCA or DCA have the same good prognosis as atherosclerotic coronary aneurysms and should be managed similarly. 1315
References 1. Morgagni JB: De Sedibus et Causis morborum. Venectus Tom I, Epis 27, Art 28, 1761 2. Munker TM, Peterson O, Vesterdal J: Congenital aneurysm of the coronary artery with an arteriovenous fistula. Acta Radio150:333-336, 1958 3. Swaye PS, Fisher LD, Litwin P, et al: Aneurysmal coronary artery disease. Circulation 67:134-138, 1983
4. Robertson T, Fisher L: Prognostic significance of coronary artery aneurysm and ectasia in the coronary artery surgery study (CASS) registry, in Shulman ST (ed): Kawasaki disease: Proceedings of the Second International Kawasaki Symposium. New York, NY, A.R. Liss, 1987, pp 325-339 5. Markis JE, Joffe CD, Cohn PF: Clinical significance of coronary arterial ectasia. Am J Cardiol 37:217-222, 1976 6. Tunick PA, Slater J, Kronzon I, Glassman E: Discrete atherosclerotic coronary artery aneurysms: A Study of 20 patients. J Am Coil Cardiol 15:279-282, 1990 7. Daoud A, Pankin D, Tulgan H, Florentin R: Aneurysms of the coronary artery. Report of ten cases and review of literature. Am J Cardio111:228-237, 1963 8. Topaz O, DiSciascio G, Cowley M, et al: Angiographic features of left main coronary artery aneurysms. Am J Cardio167:1139-1142, 1991 9. Lenihan DJ, Zeman HS, Collins GJ: Left main coronary artery aneurysm in association with severe atherosclerosis: A case report and review of the literature. Cathet Cardiovasc Diag 23:28-31, 1991 10. Rath S, Har-Zahav Y, Battler Ae, et al: Fate of non-obstructive aneurysmatic coronary artery disease: Angiographic and clinical follow-up report. Am Heart J 109:785-791,1985 11. Holmes DR, Vlietstra RE, Mock MB, et al: Angiographic changes produced by percutaneous transcutaneous coronary angioplasty. Am J Cardio151:676-683, 1983 12. Walford GD, Midei MG, Aversano TR, et al: Coronary artery Aneurysm formation following PTCA: Treatment of associated restenosis with repeat PTCA. Cathet Cardiovasc Diagn 20:77-83, 1990 13. Bal ET, Thijs Plokker H, van den Berg E, et al: Predictability and prognosis of PTCA-induced coronary artery aneurysms. Cathet Cardiovasc Diagn 22: 85-88, 1991 14. Vassaneli C, Turri M, Morando G, et ai: Coronary arterial aneurysms after PTCA-A not uncommon finding at elective follow-up angiography. Int J Cardiol 22:151-156, 1989 15. Dralle JG, Turner C, Hsu J, Replogle RL: Coronary artery aneurysms after angioplasty and atherectomy. Ann Thorac Surg 59:1030-1035, 1995 16. Prewitt KC, Laird JR, Cambier PA, Wortham DC: Late coronary artery aneurysm formation after directional atherectomy. Am Heart J 125:249-251, 1993 17. The investigators of US and European Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Registries. Acute complications of Excimer Laser Coronary Angioplasty: A detailed analysis of multicenter results. J Am Coil Cardio123:i 305-1313, 1994 18. Nakamura F, Kvasnicka J, Decoster HL, Geschwind HJ: Aneurysmal formation after successful Pulsed Laser coronary angioplasty. Cathet Cardievasc Diagn 27:125-129, 1992 19. Berkoff HA, Rowe GG: Atherosclerotic ulcerative disease and associated aneurysms of the coronary arteries. Am Heart J 90:153-158, 1975
CORONARY ARTERYANEURYSM 20. Befeler B, Aranda JM, Embi A, et al: Coronary Artery aneurysms: Study of their etiology, clinical course and effect on left ventricular function and prognosis. Am J Med 62:597-607, 1977 21. Sorrell VL, Davis MJ, Bove AA: Origins of Coronary Artery Ectasia. Lancet 347:136-137, 1996 22. England JF: Herbicides and Coronary Artery Ectasia. Med J Aust ii:140, 1981 23. Lange RL, Reid MS, Tresch DD, et al: Nonatheromatous ischemic heart disease following withdrawal from chronic industrial nitroglycerine exposure. Circulation 46:666-678, 1972 24. Vered Z, Katz M, Rath S, et al: Two dimensional Echocardiographic Analysis of Proximal Left Main Artery in Humans. Am Heart J 112:972-977, 1986 25. Tunick PA, Slater J, Pasternack P, Kronzon I: Coronary Artery Aneurysms: A Transesophageal Echocardiographic Study. Am Heart J 118:176-179, 1989 26. Cappanari TE, Daniels SR, Meyer RA, et al: Sensitivity, Specificity and Predictive Value of Two-Dimensional Echocardiography in Detecting Coronary Artery Aneurysms in Patients with Kawasaki Disease. J Am Coil Cardiol 7:355-360, 1986 27. Laurent F, Drouillard J, Dorcier F, et al: CT appearance of coronary aneurysm in Kawasaki disease. J Comput Assist Tomgr 11:151-152, 1987 28. Frey EE, Matherne GP, Mahoney LT, et al: Coronary artery aneurysms due to Kawasaki disease: Diagnosis with ultrafast CT. Radiology 167:725-726, 1988 29. Bisset GS, Strife JL, McCIoskey J, et al: MR imaging of coronary artery aneurysm in a child with Kawasaki disease. Am J Radio1152:805-807, 1989 30. Pucillo AL, Schechter AG, Moggio RA, et al: MR imaging in the definition of coronary artery anomalies. J Comput Assist Tomgr 14:171 -174, 1990 31. Jumbo Ge, Liu F, Kearney P, et al: Intravascular ultrasound approach to the diagnosis of coronary artery aneurysms. Am Heart J 130:765-761, 1995 32. Kato H, Ichinose E, Kawasaki 1-."Myocardial infarction in Kawasaki disease: Clinical analysis of 195 cases. Pediatr 108:923-927, 1986 33. Suzuki A, Kamiya T, Kuwahara N: Coronary arterial lesions in Kawasaki disease: Cardiac catheterization findings in 1100 cases. Pediatr Cardiol 7:3-9, 1986 34. Kato H: Cardiovascular involvement in Kawasaki disease: Evaluation and natural history, in Shulman ST (ed): Kawasaki disease: Proceedings of the second international Kawasaki symposium. New York, NY, A.R. Liss, 1987, pp 277-286 35. Newburger J, Takahashi M, Beiser AS, et al: A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324:1633-1639, 1991 36. Kato H, Sugimura T, Akagi T, et al: Long term consequences of Kawasaki disease. A 10 to 21 year follow up study of 594 patients. Circulation 94:1379-1385, 1996 37. Takahashi M, Mason W, Lewis AB: Regression of coronary aneurysms in patients with Kawasaki syndrome. Circulation 75:387-394, 1987
83 38. Wreford FS, Conradi SE, Cohie SD et al: Sudden death caused by coronary artery aneurysms: A late complication of Kawasaki disease. J Forensic Sci 36:51-59, 1990 39. Oliveira DB, Foale RA, Bensaid J: Coronary artery aneurysms and Kawasaki disease in an adult. Br Heart J 51:91-93, 1984 40. Ishiwata S, Fuse K, Nishiyama S, et al: Adult coronary artery disease secondary to Kawasaki disease in childhood. Am J Cardio169:692-694, 1992 41. Kodama K, Okayama H, Tamura A, et al: Kawasaki disease complicated by acute myocardial infarction due to thrombotic occlusion of coronary aneurysms 19 years after onset. Int Med 31:774-777, 1992 42. Kato H, Inoue O, Kawasaki T, et al: Adult coronary artery disease probably due to childhood Kawasaki disease. Lancet 340:1127-1129, 1992 43. Hans van den Broek, Segal BL: Coronary aneurysms in a young woman: Angiographic documentation of the natural course. Chest 64:132-134, 1973 44. Myier RK, Scheshtmann NS, Rosenblum J, et al: Multiple coronary artery aneurysms in an adult associated with extensive thrombus formation resulting in myocardial infarction: Successful treatment with intracoronay urokinase, intravenous heparin, and oral anticoagulation. Cathet Cardiovas Diagn. 24:51-54, 1991 45. Anabtawi IN, de Leon JA: Coronary ectasia: Incidence and results of coronary bypass surgery. Am Heart J 96:309-315, 1978 46. Ebert PA, Peter RH, Gunnels JC, Sabiston DC: Resecting and grafting of coronary artery aneurysm. Circulation 43:593-598, 1971 47. Swanton HR, Thomas ML, Coltart DJ, et al: Coronary artery ectasia--a variant of occlusive coronary arteriosclerosis. British Heart J 40:393-400, 1978 48. Burns CA, Cowley MJ, Wechsler AS, Verovec GW: Coronary aneurysms: A case report and review. Cathet Cardiovas Diagn 27:106-112, 1992 49. Scott DH: Aneurysm of the coronary arteries. Am Heart J 36:403-421, 1948 50. Plachta A, Speer FD: Aneurysm of the left coronary artery. Review of the literature and report of three cases. Arch Patho166:210-213, 1958 51. Maseri A, Pesola A, Marzilli M, et al: Coronary vasospasm in angina pectoris. Lancet 1:713-717, 1977 52. Freedman SB, Richmond DR, Kelly DT: Clinical studies of patients with coronary spasm. Am J Cardiol 52:67A-71A, 1983 (suppl) 53. Bove AA, Vlietstra RE: Spasm in ectatic coronary arteries. Mayo Clin Proc 60:822-826, 1985 54. Gutowski T, Tannenbaum AK, Moreyra AE: Vasospasm in a coronary artery aneurysm. Cathet Cardiovas Diagn 22:127-129, 1991 55. Aintablian A, Hamby RI, Hoffman I, Kramer RJ: Coronary ectasia: Incidence and results of coronary bypass surgery. Am Heart J 96:309-315, 1978 56. Alford W J, Stoney WS, Burrus GT, et al: Recognition
84 and operative managementof patients with arteriosclerotic coronary artery aneurysms. Ann Thorac Surg 22:317-321, 1976 57. Hartnell GG, Parnell BM, Pride RB: Coronary artery ectasia. Its prevalence and clinical significance in 4993 patients, Br Heart J 54:392-395, 1985
SYED AND LESCH 58. Falsetti HL, Carroll RJ: Coronary artery aneurysm. A review of the literature with a report of 11 new cases. Chest 69:630-636, 1976 69. Oliveros RA, Falsetti HL, Carroll RJ, et ai: Atherosclerotic coronary artery aneurysm. Arch intern Med 134: 1072-1076, 1974
Syed and Michael
Lesch
Coronary artery aneurysm is defined as coronary dilatation which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. This is an uncommon disease which has been diagnosed with increasing frequency since the advent of coronary angiography. The incidence varies from 1.5% to 5% with male dominance and a predilection for the right coronary artery. Atherosclerosis accounts for 50% of coronary aneurysms in adults. Reported complications include thrombosis and distal embolization, rupture and vasospasm. The natural history and prognosis remains obscure. Controversies persist regarding the use of surgical or medical management. The authors recommend surgery based on the severity of associated coronary stenosis rather than the mere presence of aneurysm. Medical therapy is indicated for the majority of patients and consists of antiplatelet and anticoagulant medication. Copyright © 1997 by W.B. Saunders Company
oronary artery aneurysm is an uncommon disease, which has been diagnosed with increasing frequency since the advent of coronary angiography. The first case of coronary artery aneurysm was reported by Morgagni in 1761.1 In 1958 Munker et al 2 reported the first antemortem case of coronary aneurysm diagnosed by coronary angiography. The natural history and prognosis of coronary aneurysms remains obscure. Management of these patients remains a therapeutic dilemma with published recommendations based on anecdotal experience. In an attempt to collate presently available data, a review of the literature regarding pathophysiology, management, and prognosis of this disease is presented herein.
C
Definition Aneurysmal coronary artery disease is defined as coronary dilatation which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. 3,4
Markis et al 5 used the term "ectasia" to describe coronary aneurysmal dilatation and attempted to further classify it on the basis of appearance and the number of coronary arteries involved in coronary angiography. They described type 1 as diffuse ectasia of all three major vessels, type 2 as diffuse ectasia in one vessel and localized disease in one other major vessel, and type 3 as diffuse ectasia in one vessel only. Tunick et al6 also classified aneurysms as discrete or localized abnormal dilatation of the coronary artery that is spherical or saccular. They excluded fusiform aneurysms and called them "ectasia." The authors propose that the term aneurysm be restricted to a localized, abnormal dilatation of coronary arteries which can be saccular or fusiform in shape, reserving the term ectasia to describe diffuse dilatation only. Diffuse dilatation involves the majority of the length of the artery (at least 50%). Using the term aneurysm and ectasia to define specific anatomic substrates should help to standardize the reporting of this disease and minimize discrepancies in the literature regarding management.
Incidence and Anatomic Distribution A literature search for large studies reporting the incidence and anatomic distribution of coronary artery aneurysm is summarized in Table 1. The incidence of coronary aneurysms varies from 1.5% to 5% which may be related to different criteria used to define aneurysms as previously discussed. In a postmortem study of 694 patients, Daoud et al 7 found a 1.4% incidence of coronary aneurysms. The largest antemortem series of From the Department of Internal Medicine, Division of Cardiology, Henry Ford Hospital, Detroit, MI. Address reprint requests to Michael Lesch, MD, FACC, Chairman Department of Internal Medicine, K-2, Henry Ford Hospital, Detroit, M148202. Copyright © 1997 by W.B. Saunders Company 0033-0620/97/4001-000755.00/0
Progress in Cardiovascular Diseases, Vol. 40, No. 1 (July/August), 1997: pp 77-84
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TABLE 1. Coronary Artery Aneurysms, Incidence, and Anatomic Site Authors
No. of Patients
No. of Patients With Aneurysms (%)
Markis et al5 Tunick et al6 Daoud et al7 Rath et aP° Berkoff et a119 Befeler et al2° Swanton et a147 Aintablian et a155 Hartnell et a157 Falsetti et a158 Oliveros et a159
20,087 2,457 8,422 694 1,100 1,342 1,246 1,000 1,660 4,993 742 1,500
978 (4.9) 30 (1.2) 20 (0.2) 10 (1.4) 5 (0.5) 5 (0.3) 16 (1.3) 12 (1.2) 42 (2.5) 70 (1.4) 11 (1.5) 5 (0.3)
Pooled data
45,243
1,204 (2.6%)
CASS 3'4
Number of Coronary Aneurysms RCA
LAD
LCX
LM
1,122 NR 2 8 3 0 13 6 34 52 9 4
440 NR 15 2 5 4 5 1 16 41 7 4
642 NR 4 2 3 1 8 6 14 34 10 3
35 NR 1 0 0 0 0 0 0 10 0 0
1,253 (40.4%)
1,002 (32.3%)
727 (23.4%)
46 (3.5%)
Abbreviations: NR, not reported; RCA, right coronary artery; LAD, left anterior descending artery; LCX, left circumflex; LM, left main coronary artery.
coronary aneurysms is reported by the Coronary Artery Surgery Study (CASS) registry. 3,4 This registry found an incidence of 4.9% diagnosed by coronary angiography. This is higher than other angiographic studies of coronary aneurysms reporting an incidence of 0.37% to 2.53% (Table 1). The right coronary artery seems to be the most commonly involved followed by the left anterior descending artery. Left main involvement is very rare. s,9 Although coronary aneurysms are seen at any age, those related to atherosclerosis usually appear later in life than those of a congenital or inflammatory nature. 7 Atherosclerotic or inflammatory coronary aneurysms are usually multiple and involve more than one coronary artery as compared with congenital, traumatic, or dissecting aneurysms which are mainly single. 1° Males are more commonly affected. In CASS, 3 the number of males with coronary aneurysms was significantly more than the control group (88.2% v 80.1%, P < .001).
Etiology The different etiologies which have been postulated for coronary artery aneurysms are summarized in Table 2. The most common etiology is atherosclerosis accounting for 50% of coronary aneurysms diagnosed in adults. This is followed by Kawasaki's disease and congenital aneurysms. In a review of the literature on postmortem aneurysms, Daoud et al 7 found 52% were caused
by atherosclerosis, 17% were congenital, 11% each were mycotic-embolic and dissecting, and 4% were leutic. Kawasaki's disease causing coronary artery aneurysm as a late sequelae is probably more common than congenital aneurysms especially in areas of higher prevalence, ie, Japan. 1° More recently, coronary artery aneurysms have been described as a consequence of coronary angioplasty. This was first reported by Holmes et a111 following balloon angioplasty (PTCA). Walford et al t2 reported an incidence of 0.3% in a group of 240 patients following PTCA, most of whom had dissection at the time of initial procedure. In another study, Bal et aP 3 followed 728 patients after successful PTCA and repeated angiography after a mean of 4.5 months. A coronary aneurysm at the site of PTCA was found in 3.9% of patients. In the group who had PTCA compli-
TABLE 2. Etiology of Coronary Artery Aneurysm Atherosclerosis Kawasaki disease Congenital Coronary angioplasty (balloon, laser, atherectomy) Arteritis (polyarteritis nodosa, syphilis, SLE, Takayasu's)
Mycotic Dissection Trauma Connective tissue disorders (Marfan's and Ehlers-Danlos syndromes) Metastatic tumor
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cated by dissection, the incidence of coronary aneurysms was 9% as compared with 2.9% in patients who did not have dissection complicating PTCA. Use of an oversized balloon has been proposed as a predisposing factor.14 Early and late development of coronary aneurysms following directional atherectomy (DCA) has also been well described. 15,j6 Early coronary aneurysms after DCA is related to coronary perforation leading to "pseudoaneurysm" formation, whereas late coronary aneurysms after DCA are attributed to subintimal damage. 15 A recently reported multicenter study comparing acute complications of Excimer Laser Coronary Angioplasty t7 found a 0.3% incidence of coronary aneurysm after the procedure. This rare complication has been reported with both, Ho-YAG and Excimer lasers.18
aneurysm is an abnormal vessel media which may be secondary to an extension of the intimal arteriosclerotic process. More recently, nitric oxide (NO) has been implicated in the formation of aneurysms. 21 NO stimulates the relaxation of vascular smooth muscle via the guanylate cyclase pathway and release of calcium from the endoplasmic reticulum. One possibility is that there is an imbalance between the beneficial effects of NO on coronary dilation and the potentially detrimental effects of chronic overstimulation by this endothelium derived relaxation factor. Extended exposure to herbicides causing increased production of acetylcholine22 and chronic exposure to nitrites in munitions workers 23 has been proposed to potentially stimulate NO leading to the formation of coronary aneurysms. 2~
Pathogenesis
Clinical Features
There is consensus that the majority (50%-52%) of coronary artery aneurysms are arteriosclerotic in origin. Microscopic examination reveals the usual findings of arteriosclerosis, ie, hyalinization and lipid deposition of the intima, destruction of the intima and media, focal calcification and fibrosis, cholesterol crystals, intramural hemorrhages, and foreign body giant cell reaction of the arteriosclerotic process. 5,7 Daoud et al 7 suggested the pathogenesis of aneurysms to be consequent to a poststenotic transformation of kinetic energy to potential energy or lateral pressure. However, coronary aneurysms occur in the absence of proximal stenosis. Berkoff and Rowe ~9postulated the presence of a thin, degenerated media adjacent to an intimal plaque as the primary pathological requirement leading to plaque rupture and erosion of the grumous material by the blood stream. This excavated plaque then becomes the site of aneurysm formation. Befeler et al 2° also speculated the presence of an intrinsically abnormal vessel media and an intimal injury on or about a plaque with resulting ulceration and hemorrhage giving rise to dilatation and aneurysm formation. Another theory put forward by Markis et al 5 suggests the possible cause as the intraluminal pressures against an elastic vessel wall with decreased stress tolerance due to destruction of the media. All these authors agree that the essential component in the formation of coronary
There are no clinical features characteristic of coronary artery aneurysms. Symptoms of angina or myocardial infarction are of the usual presentation. Occasionally a systolic murmur is heard over the precordium. Association with abdominal aortic aneurysm 7,2° and hypertension 5,19,2° has been postulated. Swaye et aP did not find significant differences in risk factors, subjective symptoms, or left ventricular function among patients with or without coronary aneurysms enrolled in the CASS registry. A history of Kawasaki's disease or connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome) may be helpful in suggesting the diagnosis. The possibility of coronary artery aneurysm should be considered in young patients with ischemic chest pain.
Diagnosis The diagnosis of Coronary artery aneurysm in a patient with suspected myocardial ischemia is made on the basis of cardiac imaging procedures. Coronary angiography is the gold standard in the diagnosis of coronary aneurysm and not only provides information regarding the size, shape, location, and number of aneurysms, but also delineates the presence or absence of associated stenosis. Some noninvasive methods have limited ability to define the presence of coronary aneurysm. Echocardiography, both two-dimensional
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transthoracic (2-DE) and transesophageal (TEE), have been used in the diagnosis of coronary aneurysms. 24,2s As proximal right and left coronary arteries are better visualized by TEE, this technique may have greater sensitivity. 2-DE is the primary mean of screening for coronary aneurysms in children with Kawasaki's disease. In a study of 70 patients with Kawasaki's disease, Capanneri et al, 26 found the sensitivity of 2-DE was 100% in detecting proximal coronary aneurysm, suggesting its usefulness in selecting patients for invasive coronary angiography. Coronary artery aneurysms in children have also been detected by computed tomography scanning 27,2B and magnetic resonance (MR) imaging. 29 Pucillo et aP ° described the usefulness of MR imaging in establishing the size and position in an adult patient. Jumbo Ge et al, 31 recently reported that intravascular ultrasound deployment leads to better aneurysm characterization as compared with coronary angiography and helps in differentiating between true and false aneurysms.
Kawasaki Disease Kawasaki disease or mucocutaneous lymph node syndrome deserves special mention because it is the most common cause of coronary aneurysm in children and the second most common in adults after atherosclerosis. Kawasaki disease is a systemic vasculitis syndrome which involves the medium and small size arteries, particularly coronary arteries. This syndrome was first described by Kawasaki in Japan in 1967, and is primarily a disease of childhood usually affecting children under the age of 5 years. The principal features are described as (1) fever persisting for 5 days or more, (2) skin changes with reddening of palms and soles in the early stages with subsequent membranous desquamation from finger tips in the convalescent stage, (3) polymorphous exanthema, (4) bilateral conjunctival congestion, (5) changes of the lips and oral cavity--reddening of the lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa, and (6) acute nonpurulent cervical lymphadenopathy. Although the disease is generally self-limited, 15% to 25% of children may develop coronary aneurysms 32,33 which may develop any time after day 7. Other cardiovascular lesions include myocarditis, pericarditis, and valvular involvement. Risk factors
that predict the presence of coronary aneurysms include (1) boys under 1 year of age, (2) fever lasting longer than 2 weeks, (3) elevated sedimentation rate persisting for more than 4 weeks, and (4) palpable axillary artery aneurysms. 34 Aspirin (100 mg/kg/d through day 14 of the illness and then 3-5 mg/kg/d) has been the mainstay of treatment but more recently high dose IV gamma globulin (400 mg/kg as a single dose) has been shown to reduce the development of coronary aneurysms if given early in the course of the disease. 35 One of the most exciting findings regarding coronary aneurysms in Kawasaki disease has been the occasional dramatic spontaneous regression of aneurysms in these children. In a series of 594 patients with coronary aneurysms due to Kawasaki disease reported by Kato, 36 55% of the small or moderate-sized aneurysms fully regressed Within 2 years of follow-up. Factors associated with regression include (1) age less than 1 year, (2) saccular as opposed to fusiform morphology, and (3) distal location. 37 Regression was unlikely in giant aneurysms or more than several years after onset. 36 The majority of deaths due to this illness are attributed to myocardial infarction within 6 months of symptom onset, but late presentation with acute coronary syndromes in adulthood has been well described in the literature. 38-42
Complications The natural history of coronary artery aneurysms is largely unknown. Most of the reports in the literature include small numbers of patients with short-term follow-up. C A S S 3,4 w a s the largest study of patients with coronary aneurysms but was biased towards a surgical intervention. Current recommendations are, therefore, based on anecdotal experience. Previous reports on the complications and outcomes of coronary aneurysms have reported the presence of thrombosis and distal embolization, rupture, and spasm.
Thrombosis and Distal Embolization Several case reports have described the presence of a thrombus inside the aneurysm. Daoud et al 7 in their postmortem study of 10 patients, found a thrombus inside the aneurysm in seven (70%). van den Broek and SegaP 3 described an interest-
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ing case of a 19-year-old girl diagnosed with saccular aneurysms of the left anterior descending artery and its two diagonal branches on coronary angiography. Thrombus was seen in some of these aneurysms without any obstructing lesion being identified. The patient went on to develop anteroseptal myocardial infarction and a repeat cardiac catheterization showed occlusion proximal to the sites of aneurysms. Myler et a144 also described a case of coronary aneurysm associated with extensive thrombus formation seen at coronary arteriography. R a t h e t al 1° reported a coronary angiographic study of five patients with documented coronary artery aneurysms but no stenosis. These patients underwent repeat cardiac catheterization for recurrent angina and all five had total occlusions and infarcts in the territory of the vessel with the known aneurysm. Similar observations were reported by Anabtawi et a145 and Ebert et al, 46 who found thrombus inside the coronary artery aneurysm during bypass surgery. Befeler et al 2° described a series of six cases that had segmental left ventricular dysfunction in the territory of vessels with aneurysm but without significant obstruction. The authors state that a possible explanation can be distal embolization of material originating in the coronary aneurysm. Berkoff and Rowe 19 also described severe wall motion abnormalities in patients with coronary aneurysm (6 out of 15) supporting the possibility of distal embolization of the thrombus. Abnormal blood flow patterns inside an aneurysm have been associated with thrombus formation.I°,19 Swanton et a147 measured coronary sinus blood flow in 14 patients with ectatic coronary arteries and compared it with coronary sinus blood flow in 14 patients with nonectatic coronary arteries. This limited data set suggests the presence of reduced blood flow velocity in ectatic coronary arteries favoring the formation of thrombus. Despite several authors reporting the presence of thrombus and distal embolization in coronary aneurysms, the exact incidence of this complication is unknown. In addition it is also not clear if this complication occurs more frequently in certain types of aneurysms. 48
Rupture of CoronaryAneurysms Rupture of a coronary aneurysm leading to sudden death has been a concern which led some
authors to suggest surgery to avoid this complication. 45 Daoud et al 7 reported a 12% incidence of rupture in their review of 57 cases up to 1963. Several other authors have reported rupture of coronary aneurysms. 49'5° All these reports were autopsy reviews and hence biased towards this complication as an end event. In the largest reported cohort of coronary aneurysms (CASS), Swaye et aP did not find any case of rupture in 978 patients. In a recent review, Burns et al 4s commented that since the advent of angiography and the premorten diagnosis of coronary aneurysms, no case of rupture has been documented. This led the authors to conclude that despite the theoretical risk of rupture of coronary aneurysm, this outcome seems extremely rare and unpredictable.
Vasospasm As coronary artery aneurysms originate from an abnormal vessel media, it was believed they do not have enough intact smooth muscle to generate significant vasoconstriction. Hence, coronary aneurysms were typically absent from the large series of coronary vasospasm. 51,52 Bove et aP 3 described the first two cases of vasospasm at the site of coronary aneurysm. These patients underwent coronary arteriography for recurrent chest pain, which revealed diffuse aneurysmal dilatation of the coronary arteries without substantial narrowing. Administration of intravenous ergonovine maleate led to profound generalized constriction of ectatic arteries associated with ischemic chest pain. This was promptly reversed by nitroglycerine. In another case report, Gutowski et aP 4 described spasm of the coronary artery aneurysm in response to angioplasty; the stimulus appeared to be mechanical rather than neurohormonal. These data illustrate that aneurysms of coronary arteries are capable of vasoconstriction despite a weakened and thinned media, and may have a role in the etiology of downstream ischemia.
Treatment and Prognosis The appropriate therapy for patients with coronary artery aneurysms is unknown. Controversies persist regarding the use of surgical or medical management. Published guidelines have been based on anecdotal experience rather than controlled trials. This is in part related to the rare
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nature of this disease making it difficult to conduct such a trial. Surgery has been recommended for all but minor aneurysms in view of the risk for thrombosis and rupture especially in the presence of saccular aneurysms. 45,46,56 However, there are no data available comparing medical management with surgical intervention. For atherosclerotic aneurysms, most authors agree that surgical treatment is warranted depending on the severity of associated coronary stenosis rather than the mere presence of aneurysm. Aintablian et aP 5 did not find any short-term survival difference in patients with coronary aneurysm who had bypass surgery when compared with controls. This finding was confirmed by CASS, 3 showing no survival difference in medically treated patients with coronary aneurysm and either no or nonsignificant coronary artery stenosis (<70%) as compared with controls without coronary aneurysm or significant coronary disease. Surgery when indicated, consists of coronary artery bypass with or without aneurysm ligation or excision. Outcome was excellent when the aneurysm was not included in the anastomosis. 46,56 Medical therapy is indicated for the majority of patients in whom coronary stenosis is not sufficiently significant to warrant surgery and consists of antiplatelet and anticoagulant medication. Use of anticoagulation is based on the observations of thrombus formation in association with coronary artery aneurysms and its distal embolization as previously discussed. The limited data regarding the presence of vasospasm in coronary arteries with aneurysms may constitute an indication for the addition of a vasodilator, ie, nitrates or calcium channel blockers in the management of these patients. There is consensus that late coronary aneurysms due to PTCA or DCA have the same good prognosis as atherosclerotic coronary aneurysms and should be managed similarly. 1315
References 1. Morgagni JB: De Sedibus et Causis morborum. Venectus Tom I, Epis 27, Art 28, 1761 2. Munker TM, Peterson O, Vesterdal J: Congenital aneurysm of the coronary artery with an arteriovenous fistula. Acta Radio150:333-336, 1958 3. Swaye PS, Fisher LD, Litwin P, et al: Aneurysmal coronary artery disease. Circulation 67:134-138, 1983
4. Robertson T, Fisher L: Prognostic significance of coronary artery aneurysm and ectasia in the coronary artery surgery study (CASS) registry, in Shulman ST (ed): Kawasaki disease: Proceedings of the Second International Kawasaki Symposium. New York, NY, A.R. Liss, 1987, pp 325-339 5. Markis JE, Joffe CD, Cohn PF: Clinical significance of coronary arterial ectasia. Am J Cardiol 37:217-222, 1976 6. Tunick PA, Slater J, Kronzon I, Glassman E: Discrete atherosclerotic coronary artery aneurysms: A Study of 20 patients. J Am Coil Cardiol 15:279-282, 1990 7. Daoud A, Pankin D, Tulgan H, Florentin R: Aneurysms of the coronary artery. Report of ten cases and review of literature. Am J Cardio111:228-237, 1963 8. Topaz O, DiSciascio G, Cowley M, et al: Angiographic features of left main coronary artery aneurysms. Am J Cardio167:1139-1142, 1991 9. Lenihan DJ, Zeman HS, Collins GJ: Left main coronary artery aneurysm in association with severe atherosclerosis: A case report and review of the literature. Cathet Cardiovasc Diag 23:28-31, 1991 10. Rath S, Har-Zahav Y, Battler Ae, et al: Fate of non-obstructive aneurysmatic coronary artery disease: Angiographic and clinical follow-up report. Am Heart J 109:785-791,1985 11. Holmes DR, Vlietstra RE, Mock MB, et al: Angiographic changes produced by percutaneous transcutaneous coronary angioplasty. Am J Cardio151:676-683, 1983 12. Walford GD, Midei MG, Aversano TR, et al: Coronary artery Aneurysm formation following PTCA: Treatment of associated restenosis with repeat PTCA. Cathet Cardiovasc Diagn 20:77-83, 1990 13. Bal ET, Thijs Plokker H, van den Berg E, et al: Predictability and prognosis of PTCA-induced coronary artery aneurysms. Cathet Cardiovasc Diagn 22: 85-88, 1991 14. Vassaneli C, Turri M, Morando G, et ai: Coronary arterial aneurysms after PTCA-A not uncommon finding at elective follow-up angiography. Int J Cardiol 22:151-156, 1989 15. Dralle JG, Turner C, Hsu J, Replogle RL: Coronary artery aneurysms after angioplasty and atherectomy. Ann Thorac Surg 59:1030-1035, 1995 16. Prewitt KC, Laird JR, Cambier PA, Wortham DC: Late coronary artery aneurysm formation after directional atherectomy. Am Heart J 125:249-251, 1993 17. The investigators of US and European Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Registries. Acute complications of Excimer Laser Coronary Angioplasty: A detailed analysis of multicenter results. J Am Coil Cardio123:i 305-1313, 1994 18. Nakamura F, Kvasnicka J, Decoster HL, Geschwind HJ: Aneurysmal formation after successful Pulsed Laser coronary angioplasty. Cathet Cardievasc Diagn 27:125-129, 1992 19. Berkoff HA, Rowe GG: Atherosclerotic ulcerative disease and associated aneurysms of the coronary arteries. Am Heart J 90:153-158, 1975
CORONARY ARTERYANEURYSM 20. Befeler B, Aranda JM, Embi A, et al: Coronary Artery aneurysms: Study of their etiology, clinical course and effect on left ventricular function and prognosis. Am J Med 62:597-607, 1977 21. Sorrell VL, Davis MJ, Bove AA: Origins of Coronary Artery Ectasia. Lancet 347:136-137, 1996 22. England JF: Herbicides and Coronary Artery Ectasia. Med J Aust ii:140, 1981 23. Lange RL, Reid MS, Tresch DD, et al: Nonatheromatous ischemic heart disease following withdrawal from chronic industrial nitroglycerine exposure. Circulation 46:666-678, 1972 24. Vered Z, Katz M, Rath S, et al: Two dimensional Echocardiographic Analysis of Proximal Left Main Artery in Humans. Am Heart J 112:972-977, 1986 25. Tunick PA, Slater J, Pasternack P, Kronzon I: Coronary Artery Aneurysms: A Transesophageal Echocardiographic Study. Am Heart J 118:176-179, 1989 26. Cappanari TE, Daniels SR, Meyer RA, et al: Sensitivity, Specificity and Predictive Value of Two-Dimensional Echocardiography in Detecting Coronary Artery Aneurysms in Patients with Kawasaki Disease. J Am Coil Cardiol 7:355-360, 1986 27. Laurent F, Drouillard J, Dorcier F, et al: CT appearance of coronary aneurysm in Kawasaki disease. J Comput Assist Tomgr 11:151-152, 1987 28. Frey EE, Matherne GP, Mahoney LT, et al: Coronary artery aneurysms due to Kawasaki disease: Diagnosis with ultrafast CT. Radiology 167:725-726, 1988 29. Bisset GS, Strife JL, McCIoskey J, et al: MR imaging of coronary artery aneurysm in a child with Kawasaki disease. Am J Radio1152:805-807, 1989 30. Pucillo AL, Schechter AG, Moggio RA, et al: MR imaging in the definition of coronary artery anomalies. J Comput Assist Tomgr 14:171 -174, 1990 31. Jumbo Ge, Liu F, Kearney P, et al: Intravascular ultrasound approach to the diagnosis of coronary artery aneurysms. Am Heart J 130:765-761, 1995 32. Kato H, Ichinose E, Kawasaki 1-."Myocardial infarction in Kawasaki disease: Clinical analysis of 195 cases. Pediatr 108:923-927, 1986 33. Suzuki A, Kamiya T, Kuwahara N: Coronary arterial lesions in Kawasaki disease: Cardiac catheterization findings in 1100 cases. Pediatr Cardiol 7:3-9, 1986 34. Kato H: Cardiovascular involvement in Kawasaki disease: Evaluation and natural history, in Shulman ST (ed): Kawasaki disease: Proceedings of the second international Kawasaki symposium. New York, NY, A.R. Liss, 1987, pp 277-286 35. Newburger J, Takahashi M, Beiser AS, et al: A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 324:1633-1639, 1991 36. Kato H, Sugimura T, Akagi T, et al: Long term consequences of Kawasaki disease. A 10 to 21 year follow up study of 594 patients. Circulation 94:1379-1385, 1996 37. Takahashi M, Mason W, Lewis AB: Regression of coronary aneurysms in patients with Kawasaki syndrome. Circulation 75:387-394, 1987
83 38. Wreford FS, Conradi SE, Cohie SD et al: Sudden death caused by coronary artery aneurysms: A late complication of Kawasaki disease. J Forensic Sci 36:51-59, 1990 39. Oliveira DB, Foale RA, Bensaid J: Coronary artery aneurysms and Kawasaki disease in an adult. Br Heart J 51:91-93, 1984 40. Ishiwata S, Fuse K, Nishiyama S, et al: Adult coronary artery disease secondary to Kawasaki disease in childhood. Am J Cardio169:692-694, 1992 41. Kodama K, Okayama H, Tamura A, et al: Kawasaki disease complicated by acute myocardial infarction due to thrombotic occlusion of coronary aneurysms 19 years after onset. Int Med 31:774-777, 1992 42. Kato H, Inoue O, Kawasaki T, et al: Adult coronary artery disease probably due to childhood Kawasaki disease. Lancet 340:1127-1129, 1992 43. Hans van den Broek, Segal BL: Coronary aneurysms in a young woman: Angiographic documentation of the natural course. Chest 64:132-134, 1973 44. Myier RK, Scheshtmann NS, Rosenblum J, et al: Multiple coronary artery aneurysms in an adult associated with extensive thrombus formation resulting in myocardial infarction: Successful treatment with intracoronay urokinase, intravenous heparin, and oral anticoagulation. Cathet Cardiovas Diagn. 24:51-54, 1991 45. Anabtawi IN, de Leon JA: Coronary ectasia: Incidence and results of coronary bypass surgery. Am Heart J 96:309-315, 1978 46. Ebert PA, Peter RH, Gunnels JC, Sabiston DC: Resecting and grafting of coronary artery aneurysm. Circulation 43:593-598, 1971 47. Swanton HR, Thomas ML, Coltart DJ, et al: Coronary artery ectasia--a variant of occlusive coronary arteriosclerosis. British Heart J 40:393-400, 1978 48. Burns CA, Cowley MJ, Wechsler AS, Verovec GW: Coronary aneurysms: A case report and review. Cathet Cardiovas Diagn 27:106-112, 1992 49. Scott DH: Aneurysm of the coronary arteries. Am Heart J 36:403-421, 1948 50. Plachta A, Speer FD: Aneurysm of the left coronary artery. Review of the literature and report of three cases. Arch Patho166:210-213, 1958 51. Maseri A, Pesola A, Marzilli M, et al: Coronary vasospasm in angina pectoris. Lancet 1:713-717, 1977 52. Freedman SB, Richmond DR, Kelly DT: Clinical studies of patients with coronary spasm. Am J Cardiol 52:67A-71A, 1983 (suppl) 53. Bove AA, Vlietstra RE: Spasm in ectatic coronary arteries. Mayo Clin Proc 60:822-826, 1985 54. Gutowski T, Tannenbaum AK, Moreyra AE: Vasospasm in a coronary artery aneurysm. Cathet Cardiovas Diagn 22:127-129, 1991 55. Aintablian A, Hamby RI, Hoffman I, Kramer RJ: Coronary ectasia: Incidence and results of coronary bypass surgery. Am Heart J 96:309-315, 1978 56. Alford W J, Stoney WS, Burrus GT, et al: Recognition
84 and operative managementof patients with arteriosclerotic coronary artery aneurysms. Ann Thorac Surg 22:317-321, 1976 57. Hartnell GG, Parnell BM, Pride RB: Coronary artery ectasia. Its prevalence and clinical significance in 4993 patients, Br Heart J 54:392-395, 1985
SYED AND LESCH 58. Falsetti HL, Carroll RJ: Coronary artery aneurysm. A review of the literature with a report of 11 new cases. Chest 69:630-636, 1976 69. Oliveros RA, Falsetti HL, Carroll RJ, et ai: Atherosclerotic coronary artery aneurysm. Arch intern Med 134: 1072-1076, 1974