Articles Review Article Coronary Artery Aneurysm

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of the wall integrity, as well as transition from the threelay- Third, on the basis of their size, some coronary artery ered wall to an outwardly single/double layer as a result of aneurysms have been referred to as giant coronary artery Review Article disruption of the external elastic membrane16. Pseudoaneu- aneurysms, but a precise size criterion remains unclear18-21. rysms are frequently a result of blunt chest trauma or cathe- In most of the reports, a giant aneurysm has been defined as Coronary Artery Aneurysm: A Review Article ter-based coronary interventions16. when the maximal diameter exceeds 20 mm in adults or 8 mm in children19,20. Malik F, Kalimuddin M, Ahmed N, Badiuzzaman M Pathophysiology Department of Cardiology, National Heart Foundation Hospital & Research Institute, Mirpur, Dhaka The etiology of coronary artery dilatation varies with the geographic location and the age group studied. Table 2 lists Abstract the diverse etiologies for coronary aneurysms. Coronary artery aneurysm (CAA) is defined as any coronary dilatation ≥1.5 times the diameter of the normal adjacent 11 segment or the diameter of the largest coronary vessel. It is an uncommon occurrence, yet it is described more often today Table 2: Etiologies of Coronary Artery Aneurysms than in the past as coronary angiography is now routinely used in the era of interventional cardiology. The incidence varies from 0.3% to 5.3% with male dominance and a predilection for the right coronary artery. Most cases are asymptomatic and atherosclerotic in origin in adults. Advances in imaging (IVUS, high resolution CT and MRI) have provided new insights as to the nature of angiographic coronary aneurysms. Critical assessment of the abnormal flow dynamics and pathophysiology of aneurysms has been performed and there is an improved understanding of the associated complications. Treatment may consist of surgical, percutaneous interventions or medical therapy. We present an extensive review of the recent literature highlighting the major advances in the field. (JNHFB 2016; 5 : 38-43)

Introduction With the advent of coronary angiography, coronary artery reported the first case of antemortem diagnosis of a aneurysm has been diagnosed in increasing frequency. coronary artery aneurysm diagnosed by coronary angiogra- Coronary artery aneurysm (CAA) is defined as any coronary phy. The incidence of coronary artery aneurysms ranges dilatation ≥1.5 times the diameter of the normal adjacent widely from 0.3% to 5.3% of the population, based on segment or the diameter of the largest coronary vessel1. The several angiographic studies, and a pooled analysis reports a term ectasia is reserved to mean a diffuse dilatation of a mean incidence of 1.65%8. A study from India reported an coronary artery, and an aneurysm is a focal dilatation of the incidence of 10–12%, the highest in the literature to date, vessel2. CAA can also be visualized on high resolution CT, perhaps reflecting a specific genetic and/or environmental IVUS and MRI. Although some CAA are congenital or predisposition9. The right coronary artery is the most inflammatory, most are atherosclerotic3. There is no consen- commonly affected (40–87% of aneurysms), followed by In Western countries, atherosclerotic aneurysms are most sus on its management, as some advocate conservative the left circumflex or left anterior descending artery, common (50%), followed by congenital (17%) and infec- management while others advocate more aggressive depending on the study10. Three-vessel or left main involve- tious causes (10%); and in Japan, Kawasaki disease approach4. A large aneurysm in the coronary artery makes ment is rare11. Although CAA are seen at any age, those represents the predominant cause of coronary artery 1,22,23 the blood flow turbulent and predisposes to thrombus related to atherosclerosis usually appear later in life than aneurysm . Coronary aneurysms are frequently seen in formation and coronary artery obstruction even without the those of a congenital or inflammatory nature12. Atheroscle- association with atherosclerosis, suggesting an overlap in presence of significant stenosis5. Despite this important rotic or inflammatory CAA are usually multiple and involve risk factors and pathogenesis. It has been estimated that 50% 11 anatomical abnormality of the coronary artery, the treatment more than one coronary artery as compared with congenital, of coronary aneurysms are due to atherosclerosis . The next options are poorly understood and present a therapeutic traumatic, or dissecting aneurysms which are mainly most common cause is congenital, accounting for 20–30% challenge to the interventional cardiologist. While treating single13. The incidence is higher in men than in women of coronary aneurysms. A host of inflammatory and connec- CAAs with percutaneous implantation of covered stents (2.2% vs 0.5%)1,14. tive tissue disorders have also been associated with coronary offers a less invasive option compared to surgical correc- Figure 1: Coronary artery aneurysm compared with coronary artery ectasia. aneurysms. Most well known is the association with Kawa- 5 (a, b) Drawing (a) and coronal reformatted image (b) of a coronary artery saki disease, but coronary aneurysms have also been report- tion, the short- and long-term outcomes are unknown . Classification aneurysm. Drawing (c) and volume-rendered image (d) of coronary artery Herein a review of the literature regarding incidence, classi- Coronary artery aneurysms have been classified in three ectasia n = normal15. ed in patients with Takayasu’s arteritis, lupus, rheumatoid fication, pathophysiology, clinical manifestations, manage- different ways on the basis of the composition of the vessel arthritis, Marfan syndrome, and Ehlers-Danlos syndrome. ment and prognosis of this disease is presented. wall and the morphologic structure (Table 1)15. Comparison Second, coronary artery aneurysms can be classified as Coronary aneurysms have also been noted in conjunction of coronary artery aneurysm with coronary artery ectasia is saccular or fusiform on the basis of their morphologic with infection, drug use, trauma, and percutaneous coronary 11 Incidence shown in figure 1. appearance. In saccular aneurysms, the transverse diameter intervention . Morgagni in 1761, first reported coronary artery aneurysm is greater than the longitudinal measurement of the The pathogenesis for coronary artery aneurysms is usually in a patient with coronary artery dilatation and syphilitic First, coronary artery aneurysms can be either “true” aneurysm, whereas in fusiform aneurysms, the longitudinal related to the underlying cause, but an essential prerequisite aortitis6, but it was not until 1958 when Munkner et al7 aneurysms or “false” aneurysms (pseudoaneurysms), a measurement is greater than the transverse diameter. to aneurysm formation is the presence of an abnormal tunica distinction that is based on the number of layers in the vessel Saccular aneurysms are frequently seen distal to an area of media in the vessel wall (erosion, ulceration, or hemorrhage Corresponding Author wall16. The vessel wall in true aneurysms is composed of proximal related stenosis, are often multisegmental, and are 17 in the tunica media), with resultant enlargement and Professor Fazila-Tun-Nesa Malik three layers: the tunica intima, tunica media, and tunica more prone to thrombosis and rupture . In contrast, Professor & Head, Chief of Cathlab remodeling of an arterial segment, as clearly demonstrated Department of Cardiology adventitia. Conversely, in pseudoaneurysms, there is a loss fusiform aneurysms are not known to be related to a proxi- 17 l8,14, 24–26 National Heart Foundation Hospital & Research Institute, Mirpur, Dhaka mal stenosis . in the atherosclerotic mode . More recently, CAA

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have been described as a consequence of coronary angio- Percutaneous treatment is a newer option that involves the plasty. This was first reported by Holmes et al.27 following placement of a covered stent to obstruct blood flow into the balloon angioplasty (PTCA). The incidence of coronary aneurysmal sac38. The synthetic membrane of the stent-graft artery aneurysms following PTCA ranges widely from 0.3% effectively prevents plaque protrusion, successfully sealing to 3.9%28-29. Proposed mechanisms are: Trauma from the aneurysm— a safer and less invasive alternative in the oversized balloon or high inflation pressures, coronary treatment of coronary aneurysms38 (Figure 2). These dissection, interventions in the setting of acute myocardial PTFE-covered stents, easy and rapid to deploy, have infarction, inflammatory and hypersensitivity reactions to emerged as a new tool for the treatment of coronary artery stent polymers15,30. Early and late development of coronary aneurysms4,39. Polytetrafluoroethylene has ideal characteris- aneurysms following directional atherectomy (DCA) has tics as a single layer, and it can be rolled to form a thin also been well described31,32. Early coronary aneurysms after multilayer covering that can be expanded 4 to 5 times its DCA is related to coronary perforation leading to “pseudo- original diameter (when the stent expands) without lacera- aneurysm” formation, whereas late coronary aneurysms tion or shrinkage. Furthermore, the negative charge of the after DCA are attributed to subintimal damage31. Although polymer prevents blood-protein coagulation on the tissue the molecular mechanism underlying coronary aneurysms surface and limits platelet activation and thrombus forma- has yet to be elucidated, there is evidence that matrix tion40. metalloproteinases (MMPs) have a role. The MMP are important in their ability to degrade a variety of extracellular proteins (elastin, collagen, and proteoglycans) and over-expression may predispose to aneurysm formation33. Clinical manifestations Most of the patients remain asymptomatic, and aneurysms are incidentally found during diagnostic coronary angiography or at necropsy2. When patients are symptomatic, the clinical manifestations depend on the underlying cause; in those cases associated with atherosclerosis, the clinical manifestations are similar to those seen in coronary artery disease18. Other factors that can contribute to symptoms are the extent of atherosclerosis, the presence of poor distal vessel runoff, and the development of complications such as distal embolization with myocardial ischemia, rupture with associated fistula, cardiac tamponade or hemopericardium, thrombosis, dissection, and vessel compression34. The possibility of coronary artery aneurysm should be consid- 35 ered in young patients with ischemic chest pain . Figure 2A: Aneurysmal dilatation of mid RCA Management Although several groups of investigators have reported data on coronary artery aneurysms, there are no controlled clinical studies to evaluate optimal therapy for coronary artery aneurysms because of the rarity of this condition15. However, based on several data treatment options consist of surgical, percutaneous, and medical approaches. Surgery may be considered as a means to avoid complica- tions36, and surgery is indicated in patients with obstructive coronary artery disease or evidence of embolization leading to myocardial ischemia and in those patients with evidence of enlargement of saccular coronary artery aneurysms with increased risk of rupture34. Surgical management of CAA usually involves 4 types of interventions: aneurysm ligation and distal bypass; isolated coronary artery bypass grafting; resection, or marsupialization with interposition graft, and the ideal approach has not yet been formally studied36,37. Percutaneous treatment is a newer option, with a markedly smaller data set, and includes stenting and coiling11. Figure 2B: Obliteration of CAA after covered stent deployment

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Coronary Artery Aneurysm: A Review Article Malik F et al.

Pathophysiology The etiology of coronary artery dilatation varies with the geographic location and the age group studied. Table 2 lists the diverse etiologies for coronary aneurysms.

Table 2: Etiologies of Coronary Artery Aneurysms11

Introduction With the advent of coronary angiography, coronary artery reported the first case of antemortem diagnosis of a aneurysm has been diagnosed in increasing frequency. coronary artery aneurysm diagnosed by coronary angiogra- Coronary artery aneurysm (CAA) is defined as any coronary phy. The incidence of coronary artery aneurysms ranges dilatation ≥1.5 times the diameter of the normal adjacent widely from 0.3% to 5.3% of the population, based on segment or the diameter of the largest coronary vessel1. The several angiographic studies, and a pooled analysis reports a term ectasia is reserved to mean a diffuse dilatation of a mean incidence of 1.65%8. A study from India reported an coronary artery, and an aneurysm is a focal dilatation of the incidence of 10–12%, the highest in the literature to date, vessel2. CAA can also be visualized on high resolution CT, perhaps reflecting a specific genetic and/or environmental IVUS and MRI. Although some CAA are congenital or predisposition9. The right coronary artery is the most inflammatory, most are atherosclerotic3. There is no consen- commonly affected (40–87% of aneurysms), followed by In Western countries, atherosclerotic aneurysms are most sus on its management, as some advocate conservative the left circumflex or left anterior descending artery, common (50%), followed by congenital (17%) and infec- management while others advocate more aggressive depending on the study10. Three-vessel or left main involve- tious causes (10%); and in Japan, Kawasaki disease approach4. A large aneurysm in the coronary artery makes ment is rare11. Although CAA are seen at any age, those represents the predominant cause of coronary artery 1,22,23 the blood flow turbulent and predisposes to thrombus related to atherosclerosis usually appear later in life than aneurysm . Coronary aneurysms are frequently seen in formation and coronary artery obstruction even without the those of a congenital or inflammatory nature12. Atheroscle- association with atherosclerosis, suggesting an overlap in presence of significant stenosis5. Despite this important rotic or inflammatory CAA are usually multiple and involve risk factors and pathogenesis. It has been estimated that 50% 11 anatomical abnormality of the coronary artery, the treatment more than one coronary artery as compared with congenital, of coronary aneurysms are due to atherosclerosis . The next options are poorly understood and present a therapeutic traumatic, or dissecting aneurysms which are mainly most common cause is congenital, accounting for 20–30% challenge to the interventional cardiologist. While treating single13. The incidence is higher in men than in women of coronary aneurysms. A host of inflammatory and connec- CAAs with percutaneous implantation of covered stents (2.2% vs 0.5%)1,14. tive tissue disorders have also been associated with coronary offers a less invasive option compared to surgical correc- Figure 1: Coronary artery aneurysm compared with coronary artery ectasia. aneurysms. Most well known is the association with Kawa- 5 (a, b) Drawing (a) and coronal reformatted image (b) of a coronary artery saki disease, but coronary aneurysms have also been report- tion, the short- and long-term outcomes are unknown . Classification aneurysm. Drawing (c) and volume-rendered image (d) of coronary artery Herein a review of the literature regarding incidence, classi- Coronary artery aneurysms have been classified in three ectasia n = normal15. ed in patients with Takayasu’s arteritis, lupus, rheumatoid fication, pathophysiology, clinical manifestations, manage- different ways on the basis of the composition of the vessel arthritis, Marfan syndrome, and Ehlers-Danlos syndrome. ment and prognosis of this disease is presented. wall and the morphologic structure (Table 1)15. Comparison Second, coronary artery aneurysms can be classified as Coronary aneurysms have also been noted in conjunction of coronary artery aneurysm with coronary artery ectasia is saccular or fusiform on the basis of their morphologic with infection, drug use, trauma, and percutaneous coronary 11 Incidence shown in figure 1. appearance. In saccular aneurysms, the transverse diameter intervention . Morgagni in 1761, first reported coronary artery aneurysm is greater than the longitudinal measurement of the The pathogenesis for coronary artery aneurysms is usually in a patient with coronary artery dilatation and syphilitic First, coronary artery aneurysms can be either “true” aneurysm, whereas in fusiform aneurysms, the longitudinal related to the underlying cause, but an essential prerequisite aortitis6, but it was not until 1958 when Munkner et al7 aneurysms or “false” aneurysms (pseudoaneurysms), a measurement is greater than the transverse diameter. to aneurysm formation is the presence of an abnormal tunica distinction that is based on the number of layers in the vessel Saccular aneurysms are frequently seen distal to an area of media in the vessel wall (erosion, ulceration, or hemorrhage wall16. The vessel wall in true aneurysms is composed of proximal related stenosis, are often multisegmental, and are 17 in the tunica media), with resultant enlargement and three layers: the tunica intima, tunica media, and tunica more prone to thrombosis and rupture . In contrast, fusiform aneurysms are not known to be related to a proxi- remodeling of an arterial segment, as clearly demonstrated adventitia. Conversely, in pseudoaneurysms, there is a loss l8,14, 24–26 mal stenosis17. in the atherosclerotic mode . More recently, CAA

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Pathophysiology The etiology of coronary artery dilatation varies with the geographic location and the age group studied. Table 2 lists the diverse etiologies for coronary aneurysms.

Table 2: Etiologies of Coronary Artery Aneurysms11

Introduction With the advent of coronary angiography, coronary artery reported the first case of antemortem diagnosis of a aneurysm has been diagnosed in increasing frequency. coronary artery aneurysm diagnosed by coronary angiogra- Coronary artery aneurysm (CAA) is defined as any coronary phy. The incidence of coronary artery aneurysms ranges dilatation ≥1.5 times the diameter of the normal adjacent widely from 0.3% to 5.3% of the population, based on segment or the diameter of the largest coronary vessel1. The several angiographic studies, and a pooled analysis reports a term ectasia is reserved to mean a diffuse dilatation of a mean incidence of 1.65%8. A study from India reported an coronary artery, and an aneurysm is a focal dilatation of the incidence of 10–12%, the highest in the literature to date, vessel2. CAA can also be visualized on high resolution CT, perhaps reflecting a specific genetic and/or environmental IVUS and MRI. Although some CAA are congenital or predisposition9. The right coronary artery is the most inflammatory, most are atherosclerotic3. There is no consen- commonly affected (40–87% of aneurysms), followed by In Western countries, atherosclerotic aneurysms are most sus on its management, as some advocate conservative the left circumflex or left anterior descending artery, common (50%), followed by congenital (17%) and infec- management while others advocate more aggressive depending on the study10. Three-vessel or left main involve- tious causes (10%); and in Japan, Kawasaki disease approach4. A large aneurysm in the coronary artery makes ment is rare11. Although CAA are seen at any age, those represents the predominant cause of coronary artery 1,22,23 the blood flow turbulent and predisposes to thrombus related to atherosclerosis usually appear later in life than aneurysm . Coronary aneurysms are frequently seen in formation and coronary artery obstruction even without the those of a congenital or inflammatory nature12. Atheroscle- association with atherosclerosis, suggesting an overlap in presence of significant stenosis5. Despite this important rotic or inflammatory CAA are usually multiple and involve risk factors and pathogenesis. It has been estimated that 50% 11 anatomical abnormality of the coronary artery, the treatment more than one coronary artery as compared with congenital, of coronary aneurysms are due to atherosclerosis . The next options are poorly understood and present a therapeutic traumatic, or dissecting aneurysms which are mainly most common cause is congenital, accounting for 20–30% challenge to the interventional cardiologist. While treating single13. The incidence is higher in men than in women of coronary aneurysms. A host of inflammatory and connec- CAAs with percutaneous implantation of covered stents (2.2% vs 0.5%)1,14. tive tissue disorders have also been associated with coronary offers a less invasive option compared to surgical correc- Figure 1: Coronary artery aneurysm compared with coronary artery ectasia. aneurysms. Most well known is the association with Kawa- 5 (a, b) Drawing (a) and coronal reformatted image (b) of a coronary artery saki disease, but coronary aneurysms have also been report- tion, the short- and long-term outcomes are unknown . Classification aneurysm. Drawing (c) and volume-rendered image (d) of coronary artery Herein a review of the literature regarding incidence, classi- Coronary artery aneurysms have been classified in three ectasia n = normal15. ed in patients with Takayasu’s arteritis, lupus, rheumatoid fication, pathophysiology, clinical manifestations, manage- different ways on the basis of the composition of the vessel arthritis, Marfan syndrome, and Ehlers-Danlos syndrome. ment and prognosis of this disease is presented. wall and the morphologic structure (Table 1)15. Comparison Second, coronary artery aneurysms can be classified as Coronary aneurysms have also been noted in conjunction of coronary artery aneurysm with coronary artery ectasia is saccular or fusiform on the basis of their morphologic with infection, drug use, trauma, and percutaneous coronary 11 Incidence shown in figure 1. appearance. In saccular aneurysms, the transverse diameter intervention . Morgagni in 1761, first reported coronary artery aneurysm is greater than the longitudinal measurement of the The pathogenesis for coronary artery aneurysms is usually in a patient with coronary artery dilatation and syphilitic First, coronary artery aneurysms can be either “true” aneurysm, whereas in fusiform aneurysms, the longitudinal related to the underlying cause, but an essential prerequisite aortitis6, but it was not until 1958 when Munkner et al7 aneurysms or “false” aneurysms (pseudoaneurysms), a measurement is greater than the transverse diameter. to aneurysm formation is the presence of an abnormal tunica distinction that is based on the number of layers in the vessel Saccular aneurysms are frequently seen distal to an area of media in the vessel wall (erosion, ulceration, or hemorrhage wall16. The vessel wall in true aneurysms is composed of proximal related stenosis, are often multisegmental, and are 17 in the tunica media), with resultant enlargement and three layers: the tunica intima, tunica media, and tunica more prone to thrombosis and rupture . In contrast, fusiform aneurysms are not known to be related to a proxi- remodeling of an arterial segment, as clearly demonstrated adventitia. Conversely, in pseudoaneurysms, there is a loss l8,14, 24–26 mal stenosis17. in the atherosclerotic mode . More recently, CAA

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JNHFB Jul 2016 Malik F et al. have been described as a consequence of coronary angio- Percutaneous treatment is a newer option that involves the plasty. This was first reported by Holmes et al.27 following placement of a covered stent to obstruct blood flow into the balloon angioplasty (PTCA). The incidence of coronary aneurysmal sac38. The synthetic membrane of the stent-graft artery aneurysms following PTCA ranges widely from 0.3% effectively prevents plaque protrusion, successfully sealing to 3.9%28-29. Proposed mechanisms are: Trauma from the aneurysm— a safer and less invasive alternative in the oversized balloon or high inflation pressures, coronary treatment of coronary aneurysms38 (Figure 2). These dissection, interventions in the setting of acute myocardial PTFE-covered stents, easy and rapid to deploy, have infarction, inflammatory and hypersensitivity reactions to emerged as a new tool for the treatment of coronary artery stent polymers15,30. Early and late development of coronary aneurysms4,39. Polytetrafluoroethylene has ideal characteris- aneurysms following directional atherectomy (DCA) has tics as a single layer, and it can be rolled to form a thin also been well described31,32. Early coronary aneurysms after multilayer covering that can be expanded 4 to 5 times its DCA is related to coronary perforation leading to “pseudo- original diameter (when the stent expands) without lacera- aneurysm” formation, whereas late coronary aneurysms tion or shrinkage. Furthermore, the negative charge of the after DCA are attributed to subintimal damage31. Although polymer prevents blood-protein coagulation on the tissue the molecular mechanism underlying coronary aneurysms surface and limits platelet activation and thrombus forma- has yet to be elucidated, there is evidence that matrix tion40. metalloproteinases (MMPs) have a role. The MMP are important in their ability to degrade a variety of extracellular proteins (elastin, collagen, and proteoglycans) and over-expression may predispose to aneurysm formation33. Clinical manifestations Most of the patients remain asymptomatic, and aneurysms are incidentally found during diagnostic coronary angiography or at necropsy2. When patients are symptomatic, the clinical manifestations depend on the underlying cause; in those cases associated with atherosclerosis, the clinical manifestations are similar to those seen in coronary artery disease18. Other factors that can contribute to symptoms are the extent of atherosclerosis, the presence of poor distal vessel runoff, and the development of complications such as distal embolization with myocardial ischemia, rupture with associated fistula, cardiac tamponade or hemopericardium, thrombosis, dissection, and vessel compression34. The possibility of coronary artery aneurysm should be consid- 35 ered in young patients with ischemic chest pain . Figure 2A: Aneurysmal dilatation of mid RCA Management Although several groups of investigators have reported data on coronary artery aneurysms, there are no controlled clinical studies to evaluate optimal therapy for coronary artery aneurysms because of the rarity of this condition15. However, based on several data treatment options consist of surgical, percutaneous, and medical approaches. Surgery may be considered as a means to avoid complica- tions36, and surgery is indicated in patients with obstructive coronary artery disease or evidence of embolization leading to myocardial ischemia and in those patients with evidence of enlargement of saccular coronary artery aneurysms with increased risk of rupture34. Surgical management of CAA usually involves 4 types of interventions: aneurysm ligation and distal bypass; isolated coronary artery bypass grafting; resection, or marsupialization with interposition graft, and the ideal approach has not yet been formally studied36,37. Percutaneous treatment is a newer option, with a markedly smaller data set, and includes stenting and coiling11. Figure 2B: Obliteration of CAA after covered stent deployment

40 Coronary Artery Aneurysm: A Review Article Malik F et al.

There are two possible mechanisms by which coronary Conclusion stenting might cause reduction in the size of aneurysms. One Coronary artery aneurysm is an incidental finding during is that it decreases the velocity of coronary flow through the routine coronary angiography. In the era of interventional stenosis and attenuates the hydrodynamic wall stress on the cardiology frequency of detection of CAA will be increased. aneurysm. The resulting decrease in hemodynamic forces Atherosclerosis is the most common cause of CAA. Percu- could reduce the size of aneurysm41. A second mechanism is taneous coronary interventions are rare cause of CAA, that stenting improves the degradation of the extracellular particularly after drug-eluting stent implantation. Most matrix structure through the regulation of matrix metallo- cases are asymptomatic. Although our knowledge of proteinases (MMPs)41. MMPs have been reported to be coronary artery aneurysms and their management has implicated in the pathogenesis of aneurysm development progressed, a great deal remains unknown. Answers to through increased proteolysis of extracellular matrix questions regarding optimal treatment may come from proteins42. Furthermore, endothelial MMP-9 expression is newer clinical series or the development of a multicenter coronary flow-sensitive and is up-regulated by shear registry. stress43. There is a possibility that the decreased shear stress by stenting induced down-regulation of MMP-9 activity41. References The use of PTFE-covered stents is effective and safe for large atherosclerotic aneurysms with a diameter of 6–10 1. Swaye PS, Fisher LD, Litwin PA, et al. Aneurysmal mm4. coronary artery disease. Circulation 1983;67:134 –138. 2. Packard M and Wechsler HF. Aneurysms of coronary Medical therapy is indicated for the majority of patients in arteries. Arch Intern Med 1929;43:1–14. whom coronary stenosis is not sufficiently significant to warrant surgery and consists of antiplatelet and/or 3. Maehara A, Mintz GS, Ahmed JM, Fuchs S, Castagna antithrombotic agents35. No data are currently available to MT, Pichard AD, Satler LF, Waksman R, Suddath indicate the relative merits of either approach11. In Kawasaki WO, Kent KM, Weissman NJ. An intravascular disease, the use of high-dose intravenous therapy with ultrasound classification of Angiographic coronary γ-globulin, together with aspirin, reduces the rate of occur- artery aneurysms. Am J Cardiol 2001;88(4):365–370. 44,45 rence of coronary lesions . 4. Szalat A, Durst R, Cohen A, Lotan C. Use of polytetra- fluoroethylenecovered stent for Treatment of coronary Prognosis artery aneurysm. Catheter Cardiovasc Interv. The natural history of atherosclerotic aneurysms is usually 2005;66:203–208. favorable, but there are conflicting reports8,25,46. The prognosis is directly related to the severity of the concomitant 5. Zeb M, McKenzie DB, Scott PA, Talwar S. Treatment obstructive coronary artery disease. According to the Coro- of Coronary Aneurysms With Covered Stents. J nary Artery Surgery Study registry, there was no difference Invasive Cardiol. 2012;24(9):465-469. in 5-year survival between patients with and without 6. Morgagni JB. De Sedibus et Causis morborum. Venec- 1 aneurysms who had occlusive coronary artery disease . tus Tom I, Epis 27, Art 28,1761. Rupture of aneurysms is rare and unpredictable, as reported by investigators in small series and case reports of inflam- 7. Munkner T, Petersen O, Vesterdal J. Congenital matory aneurysms, especially the mycotic ones47. In the aneurysm of the coronary artery with an Arteriove- Coronary Artery Surgery Study registry, no cases of nous fistula. Acta Radiol 1958;50(4):333–340. 1 aneurysmal rupture were documented . The prognosis for 8. Hartnell GG, Parnell BM, Pridie RB. Coronary artery aneurysms occurring after coronary catheter-based interven- ectasia: its prevalence and clinical significance in 48 tions is generally good . 4993 patients. Br Heart J. 1985;54:392–395.

In Kawasaki disease, localization and estimation of the size 9. Sharma SN, Kaul U, Sharma S, et al. Coronary arterio- of the aneurysm are necessary for risk stratification and graphic profile in young and old Indian patients with therapeutic management49. For instance, investigators have ischemic heart disease: a comparation study. Indian reported that 50% of the patients with acute Kawasaki Heart J. 1990;42:365–369. disease who had coronary artery aneurysms showed regres- 10. Villines TC, Avedissian LS, Elgin EE. Diffuse nonath- sion on the follow-up angiographic examination 1–2 years erosclerotic coronary aneurysms. Cardiol Rev. after onset, and nearly all of them were event-free during 2005;13:309 –311. long-term follow-up50,51. Factors associated with spontaneous regression include age less than 1 year, saccular 11. Cohen P and O’Gara PT. Coronary Artery Aneurysms- morphologic structure, and distal location50. Regression is A Review of the Natural History, Pathophysiology, unlikely in giant aneurysms or more than several years after and Management. Cardiology in Review 2008;16: onset. 301–304.

12. Daoud AS, Pankin D, Tulgan H, Florentin RA. Aneu- function and prognosis. Am J Med coronary aneurysm with a new polytetrafluoroeth- coronary artery aneurysm and ectasia in the Coronary rysms of the coronary artery: report of ten cases and 1977;62(4):597–607. ylene-coated stent:a case report. Catheter Cardiovasc Artery Surgery Study (CASS) registry. Prog Clin Biol review of literature. Am J Cardiol 1963;11:228–237. Interv 1999;46(4):463-465. Res 1987;250:325–339. 27. Holmes DR, Vlietstra RE, Mock MB, et al. Angio- 13. Rath S, Har-Zahav HS, Battler AE, et al. Fate of graphic changes produced by percutaneous translumi- 41. Ohtsuka M, Uchida E, Yamaguchi H, Nakajima T, 47. Topaz O, DiSciascio G, Cowley MJ, et al. Angio- non-obstructive aneurysmatic coronary artery disease: nal coronary angioplasty. Am J Cardiol Akazawa H, Funabashi N, Kobayashi Y, Shiojima I, graphic features of left main coronary artery Angiographic and clinical follow-up report. Am Heart 1983;51:676-683. Komuro I. 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Am J Cardiol 1976;37(2):217–222. ered-Stent Treatment of Coronary Aneurysm after Drug-Eluting Stent Placement -Case Report and Liter- 25. Baman TS, Cole JH, Devireddy CM, Sperlling LS. ature Review. Tex Heart Inst J 2010;37(4):449-454. Risk factors and outcomes in patients with coronary artery aneurysms. Am J Cardiol 39. Lee MS, Nero T, Makkar RR, Wilentz JR. Treatment 2004;93(12):1549–1551. of coronary aneurysm in acute myocardial infarction with AngioJet thrombectomy and JoStent coronary 26. Befeler B, Aranda MJ, Embi A, Mullin FL, El-Sherif stent graft. J Invasive Cardiol 2004;16(5):294-296. N, Lazzara R. Coronary artery aneurysms: study of the etiology, clinical course and effect on left ventricular 40. Di Mario C, Inglese L, Colombo A. Treatment of a

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48 There are two possible mechanisms by which coronary Conclusion stenting might cause reduction in the size of aneurysms. One Coronary artery aneurysm is an incidental finding during is that it decreases the velocity of coronary flow through the routine coronary angiography. In the era of interventional stenosis and attenuates the hydrodynamic wall stress on the cardiology frequency of detection of CAA will be increased. aneurysm. The resulting decrease in hemodynamic forces Atherosclerosis is the most common cause of CAA. Percu- could reduce the size of aneurysm41. A second mechanism is taneous coronary interventions are rare cause of CAA, that stenting improves the degradation of the extracellular particularly after drug-eluting stent implantation. Most matrix structure through the regulation of matrix metallo- cases are asymptomatic. Although our knowledge of proteinases (MMPs)41. MMPs have been reported to be coronary artery aneurysms and their management has implicated in the pathogenesis of aneurysm development progressed, a great deal remains unknown. Answers to through increased proteolysis of extracellular matrix questions regarding optimal treatment may come from proteins42. Furthermore, endothelial MMP-9 expression is newer clinical series or the development of a multicenter coronary flow-sensitive and is up-regulated by shear registry. stress43. There is a possibility that the decreased shear stress by stenting induced down-regulation of MMP-9 activity41. References The use of PTFE-covered stents is effective and safe for large atherosclerotic aneurysms with a diameter of 6–10 1. Swaye PS, Fisher LD, Litwin PA, et al. Aneurysmal mm4. coronary artery disease. Circulation 1983;67:134 –138. 2. Packard M and Wechsler HF. Aneurysms of coronary Medical therapy is indicated for the majority of patients in arteries. Arch Intern Med 1929;43:1–14. whom coronary stenosis is not sufficiently significant to warrant surgery and consists of antiplatelet and/or 3. Maehara A, Mintz GS, Ahmed JM, Fuchs S, Castagna antithrombotic agents35. No data are currently available to MT, Pichard AD, Satler LF, Waksman R, Suddath indicate the relative merits of either approach11. In Kawasaki WO, Kent KM, Weissman NJ. An intravascular disease, the use of high-dose intravenous therapy with ultrasound classification of Angiographic coronary γ-globulin, together with aspirin, reduces the rate of occur- artery aneurysms. Am J Cardiol 2001;88(4):365–370. 44,45 rence of coronary lesions . 4. Szalat A, Durst R, Cohen A, Lotan C. Use of polytetra- fluoroethylenecovered stent for Treatment of coronary Prognosis artery aneurysm. Catheter Cardiovasc Interv. The natural history of atherosclerotic aneurysms is usually 2005;66:203–208. favorable, but there are conflicting reports8,25,46. The prognosis is directly related to the severity of the concomitant 5. Zeb M, McKenzie DB, Scott PA, Talwar S. Treatment obstructive coronary artery disease. According to the Coro- of Coronary Aneurysms With Covered Stents. J nary Artery Surgery Study registry, there was no difference Invasive Cardiol. 2012;24(9):465-469. in 5-year survival between patients with and without 6. Morgagni JB. De Sedibus et Causis morborum. Venec- 1 aneurysms who had occlusive coronary artery disease . tus Tom I, Epis 27, Art 28,1761. Rupture of aneurysms is rare and unpredictable, as reported by investigators in small series and case reports of inflam- 7. Munkner T, Petersen O, Vesterdal J. Congenital matory aneurysms, especially the mycotic ones47. In the aneurysm of the coronary artery with an Arteriove- Coronary Artery Surgery Study registry, no cases of nous fistula. Acta Radiol 1958;50(4):333–340. 1 aneurysmal rupture were documented . The prognosis for 8. Hartnell GG, Parnell BM, Pridie RB. Coronary artery aneurysms occurring after coronary catheter-based interven- ectasia: its prevalence and clinical significance in 48 tions is generally good . 4993 patients. Br Heart J. 1985;54:392–395.

JNHFB Jul 2016 Malik F et al.

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Coronary Artery Aneurysm: A Review Article Malik F et al.

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