- Email: [email protected]
Multivessel giant coronary aneurysms: Case report and literature review
CASE REPORT
Multivessel giant coronary aneurysms: Case report and literature review
Here, we report a case of 47-year-old male, nondiabetic, nonhypertensive, smoker who presented to our hospital with complaints of retrosternal chest pain of more than 12-hours duration. His electrocardiogram revealed ST-elevation in leads V1−V4 with reciprocal changes in leads II, III, and aVF. His vitals at the time of admission were heart rate 92 bpm, blood pressure 126/84 mmHg, RR 28/min, Spo2 96% on room air. Blood biochemical and hematological parameters were normal. With the diagnosis of anterior septal ST-segment elevation myocardial infarction (STEMI), he was treated with lowmolecular-weight heparin (LMWH), aspirin, clopidogrel, statin, beta blocker, and angiotensin-converting-enzyme inhibitor (ACEI). Coronary angiogram was done on the third day of his admission, as he continued to have post-myocardial infarction (MI) angina, despite optimal medical treatment. Coronary angiography revealed a 9 mm × 9 mm aneurysm involving the distal part of the left main coronary artery (LMCA) (Figure 1). There was another large calcified aneurysm measuring 12 mm × 23 mm, involving the origin of the left anterior descending (LAD) artery (Figure 2). A third aneurysm was found in the proximal right coronary artery (RCA) (Figure 3) which measured
Trinath Kumar Mishra, MD DM FACC FICC* SN Routray, MD DM FICC** Biswajit Das, MD DM FICC† ChhabiSatpathy, MD DM FICC FCSI† CK Mishra, MD DM FICC†
ABSTRACT Coronary aneurysms have frequently been reported having varied incidence and etiology. Atherosclerotic coronary artery disease (CAD) is the predominant cause particularly in adults. Other causes include Kawasaki disease, Marfan syndrome, Behcet disease, and use of stents. Giant coronary aneuryms, measuring ≥ 8 mm in diameter, are rare entities. Multivessel coronary artery involvement is still rare. Exact pathogenetic mechanisms have not been defined although many hypotheses have been proposed. Prognosis is generally favorable. Management includes control of risk factors and surgical intervention. No consensus is there regarding exact management strategy. Here, we report a case of giant coronary aneurysms involving multiple coronary arteries, who presented with ST-segment elevated acute myocardial infarction. Keywords Coronary artery disease, giant coronary aneurysm, multivessel coronary aneurysm
INTRODUCTION Coronary artery aneurysm is found in 0.3–5% of patients undergoing coronary angiography.1 Giant coronary aneurysms have been reported less frequently, with a reported frequency of 0.02%.2 Multivessel giant coronary aneurysms have been reported occasionally.3 Although, many causes have been described, atherosclerosis remains the main etiology comprising about 50% of the cases of coronary aneurysms. The exact pathogenesis has not been defined as yet, but an inflammatory process underlies many such conditions.4 Angiography is the mainstay for diagnosis. The prognosis is generally favorable.
Figure 1 Calcified aneurysm of left anterior descending artery (double arrow).
*Professor and Head, **Professor, †Assistant Professor, Department of Cardiology, SCB Medical College, Cuttack – 753007, Orissa, India. Correspondence: Dr. Trinath Kumar Mishra, Professor and Head, Department of Cardiology, SCB Medical College, Cuttack – 753007, Orissa, India. E-mail: [email protected]
JICC Vol 2 Number 2
Figure 2 Aneurysm of left main coronary artery encroaching on left circumflex. 83
© 2012 ICC
Mishra, et al
The RCA is the most frequently involved vessel (40–61%), followed by the LAD coronary artery (15–32%) and the left circumflex artery (15–23%). Left main trunk involvement is rare (0.1–3.5%), and its presence is usually associated with significant underlying two- or three-vessel CAD.5 Comparing nearly 1000 patients with aneurysms to those with coronary artery stenoses but no aneurysms, patients with aneurysms were more likely to have three-vessel disease, a history of MI, and to be male. Patients with aneurysms, however, were less likely to have a family history of CAD and did not differ from patients without aneurysms in left ventricular ejection fraction (LVEF) or in the incidence of hypertension (HTN), diabetes, smoking, peripheral vascular disease, hyperlipidemia, or angina.10 Figure 3 Aneurysm of right coronary artery.
9 mm × 12 mm in size. Left anterior descending artery was diffusely diseased with collateral filling from the RCA. Flows in the other two arteries were normal. A diagnosis of coronary artery disease (CAD) with multiple giant coronary aneurysms was made and he was managed conservatively.
ETIOLOGY Coronary aneurysms are frequently seen in association with atherosclerosis, suggesting an overlap in risk factors and pathogenesis. It has been estimated that 50% of coronary aneurysms are due to atherosclerosis. The next most common cause is congenital, accounting for 20–30% of coronary aneurysms. A host of inflammatory and connective tissue disorders have also been associated with coronary aneurysms. Most well known is the association with Kawasaki disease, but coronary aneurysms have also been reported in patients with Takayasu’s arteritis, lupus, rheumatoid arthritis, Marfan syndrome, and Ehlers-Danlos syndrome. Coronary aneurysms have also been noted in conjunction with infection, drug use, trauma, and percutaneous coronary intervention.10 Drug-eluting stent (DES) implantation is also emerging as a significant risk factor for coronary aneurysm.13 Table 1 depicts various causes of coronary aneurysm.
DISCUSSION Coronary aneurysms are defined as a localized dilatation that exceeds 1.5 times the diameter of the adjacent segment of artery.5 Aneurysms can be saccular (transverse larger than the longitudinal axis) or fusiform (longitudinal at least twice the transverse axis).5 These should be distinguished from coronary artery ectasia in which there is diffuse dilatation involving > 50% of the coronary artery.5 Definition of giant coronary aneurysm engenders controversy. According to Japanese Ministry of Health criteria, giant coronary aneurysm is defined as ≥ 8 mm of the internal luminal diameter.6 But some case reports have used the criteria of ≥ 20 mm.3 Others have used different criteria for adults (≥ 20 mm) and for children (≥ 8 mm).5 According to the American Heart Association statement, aneurysms may be classified as small (< 5 mm internal diameter), medium (5–8 mm internal diameter), or giant (> 8 mm internal diameter).7 One of the earliest descriptions of these anomalies was by Morgagni in 1761, with one of the first case series, comprised of 21 patients, reported in 1929.8 Munker et al reported the first antemortem case diagnosed by coronary angiography in 1958.9 Based on several angiographic studies, the incidence of coronary artery aneurysms ranges widely from 0.3−5.3% of the population, and a pooled analysis reports a mean incidence of 1.65%.10 A study from India reported an incidence of 10–12%, the highest in the literature to date, perhaps reflecting a specific genetic and/or environmental predisposition.11 The coronary artery surgery study (CASS) registry of 20,087 consecutive patients undergoing coronary angiography for suspected CAD is the largest series of patients with coronary aneurysms. The CASS registry demonstrates a 4.9% incidence of coronary aneurysms (978 patients). Patients with both aneurysms and coronary ectasia were included in this study.12 JICC Vol 2 Number 2
PATHOGENESIS Exact pathophysiologic basis of coronary artery aneurysm is not established. Inflammation seems to play the central role. Inflammation spilling over into the tunica media from the tunica intima has been hypothesized to link atherosclerosis to aneurysm formation in susceptible individuals.4 Although, the molecular mechanism underlying coronary aneurysms has yet to be elucidated, there is evidence that matrix metalloproteinases (MMPs) have a role. Increased proteolysis of extracellular matrix proteins is probably a mechanism of coronary artery aneurysm formation. Matrix metalloproteinase 1 (interstitial collagenase), matrix metalloproteinase 2 (gelatinase A), matrix metalloproteinase 3 (stromelysin 1), matrixmetalloproteinase 9 (gelatinase B), and matrix metalloproteinase 12 (macrophage metalloelastase) are capable of degrading essentially all components of arterial wall matrix (elastin, collagen, proteoglycans, laminin, fibronectin, etc.) and are present in elevated concentrations in aortic aneurysms, while there are decreased levels of tissue inhibitors of matrix metalloproteinases. The matrix 84
© 2012 ICC
Multivessel giant coronary aneurysms: Case report and literature review
elucidated to involve mutations in the receptors for TGF-β, suggesting that the pathogenesis of aneurysm formation in all these syndromes is mediated by an excess of active TGF-β. Cystic medial degeneration is commonly a feature of the aneurysms in Marfan syndrome, so its presence in a coronary artery aneurysm may be indicative of a congenital genetic defect causing an excess of active TGF-β. Cystic medial degeneration is also, however, commonly seen in the aortic aneurysms of late middle-aged and elderly patients without Marfan syndrome, but it could be indicative of an excess of active TGF-β in them as well. Cocaine may also cause coronary artery aneurysms by inducing an excess of active TGF-β. The pathogenesis has implications for treatment. The TGF-β can be inhibited by angiotensin-II type I receptor antagonists such as losartan, which can prevent aortic aneurysms in a mouse model of Marfan syndrome. Perhaps such drugs could prevent coronary aneurysms as well. The secretion of metalloproteinases 1, 2, 3, and 9 from macrophages and vascular smooth muscle cells can be inhibited by the statins (hydroxymethylglutaryl coenzyme A reductase inhibitors) simvastatin, lovastatin, and cerivastatin. This suggests the possibility that these drugs may have value in inhibiting the tunica media destruction characteristic of coronary artery aneurysms.19
Table 1 Etiology of coronary artery aneurysms. • Atherosclerosis • Congenital • Inflammatory disorders Kawasaki disease, Takayasu’s arteritis, lupus, rheumatoid arthritis, Wegener’s granulomatosis, giant cell arteritis, ChurgStrauss, microscopic polyangiitis, antiphospholipid antibody syndrome, Behcet’s, sarcoid, polyarteritis nodosa, CREST syndrome, ankylosing spondylitis, Reiter syndrome, psoriatic arthritis, inflammatory bowel disease • Connective tissue disorders Marfan syndrome, Ehlers-Danlos, fibromuscular dysplasia, polycystic kidney disease • Infectious Bacterial, mycobacterial, fungal, syphilis, lyme, septic emboli, mycotic aneurysm, human immunodeficiency virus • Drug related • Cocaine, amphetamines, protease inhibitors • Traumatic • Iatrogenic
metalloproteinase-3 5A allele is associated with higher promoter activity for transcription of the gene, and this allele is more common in patients with coronary artery aneurysms plus atherosclerosis than patients with only coronary atherosclerosis. Twenty-five in patients with Kawasaki disease, those with coronary artery lesions have higher plasma levels of both matrix metalloproteinase 3 and matrix metalloproteinase 9.14 Coronary artery aneurysms have been increasingly reported as a complication of DES.15 Aneurysm formation is a recognized complication of coronary artery stenting with bare-metal stents and of angioplasty without stenting.16 To some extent, these aneurysms are presumably due to inflation of the angioplasty balloon as a simple mechanical consequence of the procedure. That is, however, an unlikely explanation for aneurysms developing for months to years after DES placement. The drugs in these stents are immunosuppressants such as sirolimus, which inhibit inflammation, or chemotherapeutic agents such as paclitaxel, which inhibit cell proliferation and, in turn, inflammation. As long as the drug is eluting, hypersensitivity vasculitis is presumably inhibited, but once the drug has eluted, the polymer in which the drug is embedded may elicit a hypersensitivity reaction uninhibited by the drug. This concept is supported by the finding of an eosinophilic infiltrate in the few cases of such post-stent coronary artery aneurysms examined histologically.17 Connective tissue diseases such as Marfan syndrome can cause aneurysms without atherosclerosis. Marfan syndrome is associated with mutations in the gene for fibrillin (a major component of microfibrils associated with elastin fibers), and fibrillin is homologous with the family of latent transforming growth factor (TGF-β)-binding proteins, which hold TGF-β in an inactive complex.18 Other aneurysm syndromes have recently been JICC Vol 2 Number 2
NATURAL HISTORY OF GIANT CORONARY ANEURYSM Giant coronary aneurysms are rare, with an incidence of 0.02%. Li et al were the first to report their surgical experience with giant coronary aneurysms over an 8-year period.20 Because of the rarity of giant coronary aneurysms, the exact natural progression is unknown. It appears that all of them will develop complications at some point and will likely require surgical intervention. Patients are often asymptomatic when they are diagnosed with coronary aneurysms, but they may present with exercise-induced angina, unstable angina, and, occasionally, MI. Potential complications include thrombosis, embolism, rupture, fistula to the cardiac chambers, and endocarditis. Most giant coronary aneurysms reported in the medical literature have involved the RCA adjacent to the right atrium.20
MANAGEMENT There appears to be no significant difference in survival between patients who have aneurysmal or non-aneurysmal CAD when factors such as HTN, diabetes mellitus, lipid abnormalities, family history, cigarette smoking, MI, and peripheral vascular disease are examined. Given the frequency of thrombosis in coronary artery aneurysms, antiplatelet therapy (with aspirin or clopidogrel) or anticoagulation (with warfarin) has predictably been reported useful in the medical management of these aneurysms. Stenting and coil embolization have been used in the nonsurgical management of coronary aneurysms. It is unknown whether size alone is an indication for surgical 85
© 2012 ICC
Mishra, et al
5.
intervention. Some surgeons believe that surgical repair is mandatory when a coronary aneurysm is 3 times larger than the original vessel diameter. Other techniques have included reconstruction and direct repair via mobilization of the inflow and outflow portions and end-to-end anastomosis. Percutaneous management of giant aneurysms have also been advocated. This includes coil embolization, covered graft and stent graft implantation. The best strategy is that the treatment should be individualized in view of lack of randomized trials.
Mariana Díaz-Zamudio, UlisesBacilio-Pérez, Mary C. Herrera-Zarza, et al. Coronary artery aneurysms and ectasia: role of coronary CT angiography. RadioGraphics 2009;29:1939–54. 6. Kamiya T. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Annual Report of Research Committee on Kawasaki Disease. Tokyo: Japanese Ministry of Health and Welfare 1983:1–13. 7. Dajani AS, Taubert KA, Takahashi M, et al. Guidelines for long-term management of patients with Kawasaki disease: report from the Committee on rheumatic fever, endocarditis, and Kawasaki disease, Council on cardiovascular disease in the young, American Heart Association. Circulation 1994;89:916–22. 8. Falsetti HL, Carrol RJ. Coronary artery aneurysm: a review of the literature with a report of 11 new cases. Chest 1976;69:630–6. 9. Munkner T, Petersen O, Vesterdal J. Congenital aneurysm of the coronary artery with an arteriovenous fistula. Acta Radiol 1958;50: 333–40. 10. Cohen P, O’Gara PT. Coronary artery aneurysms: a review of the natural
CONCLUSION Coronary artery aneurysm is found in 0.3–5% of patients undergoing coronary angiography. Giant coronary aneurysms have been reported less frequently, with a reported frequency of 0.02%. Multivessel giant coronary aneurysms have been reported occasionally. Although, varied etiology have been described, atherosclerosis is the main cause comprising about 50% of the cases of coronary aneurysms. Other etiologies include congenital cases, inflammatory conditions like Kawasaki disease, Behchet syndrome, systemic lupus erythematosus, connective tissue disorders, and cocaine abuse. Drug-eluting stents implantation is also emerging as a significant cause. The exact pathogenesis has not been diagnosed as yet, but an inflammatory process is underlying in many such conditions. Symptoms, if present, are usually related to myocardial ischemia. Angiography is the mainstay for diagnosis. The prognosis is generally favorable. Thromboembolic complications are rare with antiplatelet therapy, and spontaneous rupture generally is rare but occurs more commonly in Kawasaki disease. Management varies from antithrombotic therapy to surgical ligation. Controlling coronary heart disease risk factors sharply affects the prognosis in patients with coronary artery aneurysm. ♦
11.
12. 13.
14.
15.
16. REFERENCES 1. Packard M, Wechsler HF. Aneurysms of coronary arteries. Arch Intern Med 1929;43:1–14. 2. Li D, Wu Q, Sun L, et al. Surgical treatment of giant coronary artery aneurysm. J Thorac Cardiovasc Surg 2005;130:817–21. 3. Rammohan M, Ebel R, Crosby M, Almassi GH. Multiple giant coronary artery aneuryms. Tex Heart Inst J 2009;36:244–6. 4. Nichols L, Lagana S, Parwani A. Coronary artery aneurysm, a review and hypothesis regarding etiology. Arch Pathol Lab Med 2008;132: 823–8.
JICC Vol 2 Number 2
17.
18. 19. 20.
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history, pathophysiology, and management. Cardiol Revi 2008;16: 301–4. Sharma SN, Kaul U, Sharma S, et al. Coronary arteriographic profile in young and old Indian patients with ischemic heart disease: a comparative study. Indian Heart J 1990;42:365–9. Swayze PS, Fisher LD, Litwin PA, et al. Aneurysmal coronary artery disease. Circulation 1983;67:134–8. Aoki J, Kirtane A, Leon MB, Dangas G. Coronary artery aneurysms after drug-eluting stent implantation. J Am Coll Cardiol Intv 2008;1: 14–21. Senzaki H, Masutani S, Kobayashi J, et al. Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease. Circulation 2001;104:860–3. Luthra S, Tatoulis J, Warren RJ. Drug-eluting stent-induced left anterior descending coronary artery aneurysm: repair by pericardial patch—where are we headed? Ann Thorac Surg 2007;83:1530–2. Berkalp B, Kervancioglu C, Oral D. Coronary artery aneurysm formation after balloon angioplasty and stent implantation. Int J Cardiol 1999;69:65–70. Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent. Circulation 2004;109:701–5. Gelb BD. Marfan’s syndrome and related disorders: more tightly connected than we thought. N Engl J Med 2006;355:841–4. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006;355:788–98. Li D, Wu Q, Sun L, et al. Surgical treatment of giant coronary artery aneurysm. J Thorac Cardiovasc Surg 2005;130:817–21.
© 2012 ICC
Multivessel giant coronary aneurysms: Case report and literature review
Here, we report a case of 47-year-old male, nondiabetic, nonhypertensive, smoker who presented to our hospital with complaints of retrosternal chest pain of more than 12-hours duration. His electrocardiogram revealed ST-elevation in leads V1−V4 with reciprocal changes in leads II, III, and aVF. His vitals at the time of admission were heart rate 92 bpm, blood pressure 126/84 mmHg, RR 28/min, Spo2 96% on room air. Blood biochemical and hematological parameters were normal. With the diagnosis of anterior septal ST-segment elevation myocardial infarction (STEMI), he was treated with lowmolecular-weight heparin (LMWH), aspirin, clopidogrel, statin, beta blocker, and angiotensin-converting-enzyme inhibitor (ACEI). Coronary angiogram was done on the third day of his admission, as he continued to have post-myocardial infarction (MI) angina, despite optimal medical treatment. Coronary angiography revealed a 9 mm × 9 mm aneurysm involving the distal part of the left main coronary artery (LMCA) (Figure 1). There was another large calcified aneurysm measuring 12 mm × 23 mm, involving the origin of the left anterior descending (LAD) artery (Figure 2). A third aneurysm was found in the proximal right coronary artery (RCA) (Figure 3) which measured
Trinath Kumar Mishra, MD DM FACC FICC* SN Routray, MD DM FICC** Biswajit Das, MD DM FICC† ChhabiSatpathy, MD DM FICC FCSI† CK Mishra, MD DM FICC†
ABSTRACT Coronary aneurysms have frequently been reported having varied incidence and etiology. Atherosclerotic coronary artery disease (CAD) is the predominant cause particularly in adults. Other causes include Kawasaki disease, Marfan syndrome, Behcet disease, and use of stents. Giant coronary aneuryms, measuring ≥ 8 mm in diameter, are rare entities. Multivessel coronary artery involvement is still rare. Exact pathogenetic mechanisms have not been defined although many hypotheses have been proposed. Prognosis is generally favorable. Management includes control of risk factors and surgical intervention. No consensus is there regarding exact management strategy. Here, we report a case of giant coronary aneurysms involving multiple coronary arteries, who presented with ST-segment elevated acute myocardial infarction. Keywords Coronary artery disease, giant coronary aneurysm, multivessel coronary aneurysm
INTRODUCTION Coronary artery aneurysm is found in 0.3–5% of patients undergoing coronary angiography.1 Giant coronary aneurysms have been reported less frequently, with a reported frequency of 0.02%.2 Multivessel giant coronary aneurysms have been reported occasionally.3 Although, many causes have been described, atherosclerosis remains the main etiology comprising about 50% of the cases of coronary aneurysms. The exact pathogenesis has not been defined as yet, but an inflammatory process underlies many such conditions.4 Angiography is the mainstay for diagnosis. The prognosis is generally favorable.
Figure 1 Calcified aneurysm of left anterior descending artery (double arrow).
*Professor and Head, **Professor, †Assistant Professor, Department of Cardiology, SCB Medical College, Cuttack – 753007, Orissa, India. Correspondence: Dr. Trinath Kumar Mishra, Professor and Head, Department of Cardiology, SCB Medical College, Cuttack – 753007, Orissa, India. E-mail: [email protected]
JICC Vol 2 Number 2
Figure 2 Aneurysm of left main coronary artery encroaching on left circumflex. 83
© 2012 ICC
Mishra, et al
The RCA is the most frequently involved vessel (40–61%), followed by the LAD coronary artery (15–32%) and the left circumflex artery (15–23%). Left main trunk involvement is rare (0.1–3.5%), and its presence is usually associated with significant underlying two- or three-vessel CAD.5 Comparing nearly 1000 patients with aneurysms to those with coronary artery stenoses but no aneurysms, patients with aneurysms were more likely to have three-vessel disease, a history of MI, and to be male. Patients with aneurysms, however, were less likely to have a family history of CAD and did not differ from patients without aneurysms in left ventricular ejection fraction (LVEF) or in the incidence of hypertension (HTN), diabetes, smoking, peripheral vascular disease, hyperlipidemia, or angina.10 Figure 3 Aneurysm of right coronary artery.
9 mm × 12 mm in size. Left anterior descending artery was diffusely diseased with collateral filling from the RCA. Flows in the other two arteries were normal. A diagnosis of coronary artery disease (CAD) with multiple giant coronary aneurysms was made and he was managed conservatively.
ETIOLOGY Coronary aneurysms are frequently seen in association with atherosclerosis, suggesting an overlap in risk factors and pathogenesis. It has been estimated that 50% of coronary aneurysms are due to atherosclerosis. The next most common cause is congenital, accounting for 20–30% of coronary aneurysms. A host of inflammatory and connective tissue disorders have also been associated with coronary aneurysms. Most well known is the association with Kawasaki disease, but coronary aneurysms have also been reported in patients with Takayasu’s arteritis, lupus, rheumatoid arthritis, Marfan syndrome, and Ehlers-Danlos syndrome. Coronary aneurysms have also been noted in conjunction with infection, drug use, trauma, and percutaneous coronary intervention.10 Drug-eluting stent (DES) implantation is also emerging as a significant risk factor for coronary aneurysm.13 Table 1 depicts various causes of coronary aneurysm.
DISCUSSION Coronary aneurysms are defined as a localized dilatation that exceeds 1.5 times the diameter of the adjacent segment of artery.5 Aneurysms can be saccular (transverse larger than the longitudinal axis) or fusiform (longitudinal at least twice the transverse axis).5 These should be distinguished from coronary artery ectasia in which there is diffuse dilatation involving > 50% of the coronary artery.5 Definition of giant coronary aneurysm engenders controversy. According to Japanese Ministry of Health criteria, giant coronary aneurysm is defined as ≥ 8 mm of the internal luminal diameter.6 But some case reports have used the criteria of ≥ 20 mm.3 Others have used different criteria for adults (≥ 20 mm) and for children (≥ 8 mm).5 According to the American Heart Association statement, aneurysms may be classified as small (< 5 mm internal diameter), medium (5–8 mm internal diameter), or giant (> 8 mm internal diameter).7 One of the earliest descriptions of these anomalies was by Morgagni in 1761, with one of the first case series, comprised of 21 patients, reported in 1929.8 Munker et al reported the first antemortem case diagnosed by coronary angiography in 1958.9 Based on several angiographic studies, the incidence of coronary artery aneurysms ranges widely from 0.3−5.3% of the population, and a pooled analysis reports a mean incidence of 1.65%.10 A study from India reported an incidence of 10–12%, the highest in the literature to date, perhaps reflecting a specific genetic and/or environmental predisposition.11 The coronary artery surgery study (CASS) registry of 20,087 consecutive patients undergoing coronary angiography for suspected CAD is the largest series of patients with coronary aneurysms. The CASS registry demonstrates a 4.9% incidence of coronary aneurysms (978 patients). Patients with both aneurysms and coronary ectasia were included in this study.12 JICC Vol 2 Number 2
PATHOGENESIS Exact pathophysiologic basis of coronary artery aneurysm is not established. Inflammation seems to play the central role. Inflammation spilling over into the tunica media from the tunica intima has been hypothesized to link atherosclerosis to aneurysm formation in susceptible individuals.4 Although, the molecular mechanism underlying coronary aneurysms has yet to be elucidated, there is evidence that matrix metalloproteinases (MMPs) have a role. Increased proteolysis of extracellular matrix proteins is probably a mechanism of coronary artery aneurysm formation. Matrix metalloproteinase 1 (interstitial collagenase), matrix metalloproteinase 2 (gelatinase A), matrix metalloproteinase 3 (stromelysin 1), matrixmetalloproteinase 9 (gelatinase B), and matrix metalloproteinase 12 (macrophage metalloelastase) are capable of degrading essentially all components of arterial wall matrix (elastin, collagen, proteoglycans, laminin, fibronectin, etc.) and are present in elevated concentrations in aortic aneurysms, while there are decreased levels of tissue inhibitors of matrix metalloproteinases. The matrix 84
© 2012 ICC
Multivessel giant coronary aneurysms: Case report and literature review
elucidated to involve mutations in the receptors for TGF-β, suggesting that the pathogenesis of aneurysm formation in all these syndromes is mediated by an excess of active TGF-β. Cystic medial degeneration is commonly a feature of the aneurysms in Marfan syndrome, so its presence in a coronary artery aneurysm may be indicative of a congenital genetic defect causing an excess of active TGF-β. Cystic medial degeneration is also, however, commonly seen in the aortic aneurysms of late middle-aged and elderly patients without Marfan syndrome, but it could be indicative of an excess of active TGF-β in them as well. Cocaine may also cause coronary artery aneurysms by inducing an excess of active TGF-β. The pathogenesis has implications for treatment. The TGF-β can be inhibited by angiotensin-II type I receptor antagonists such as losartan, which can prevent aortic aneurysms in a mouse model of Marfan syndrome. Perhaps such drugs could prevent coronary aneurysms as well. The secretion of metalloproteinases 1, 2, 3, and 9 from macrophages and vascular smooth muscle cells can be inhibited by the statins (hydroxymethylglutaryl coenzyme A reductase inhibitors) simvastatin, lovastatin, and cerivastatin. This suggests the possibility that these drugs may have value in inhibiting the tunica media destruction characteristic of coronary artery aneurysms.19
Table 1 Etiology of coronary artery aneurysms. • Atherosclerosis • Congenital • Inflammatory disorders Kawasaki disease, Takayasu’s arteritis, lupus, rheumatoid arthritis, Wegener’s granulomatosis, giant cell arteritis, ChurgStrauss, microscopic polyangiitis, antiphospholipid antibody syndrome, Behcet’s, sarcoid, polyarteritis nodosa, CREST syndrome, ankylosing spondylitis, Reiter syndrome, psoriatic arthritis, inflammatory bowel disease • Connective tissue disorders Marfan syndrome, Ehlers-Danlos, fibromuscular dysplasia, polycystic kidney disease • Infectious Bacterial, mycobacterial, fungal, syphilis, lyme, septic emboli, mycotic aneurysm, human immunodeficiency virus • Drug related • Cocaine, amphetamines, protease inhibitors • Traumatic • Iatrogenic
metalloproteinase-3 5A allele is associated with higher promoter activity for transcription of the gene, and this allele is more common in patients with coronary artery aneurysms plus atherosclerosis than patients with only coronary atherosclerosis. Twenty-five in patients with Kawasaki disease, those with coronary artery lesions have higher plasma levels of both matrix metalloproteinase 3 and matrix metalloproteinase 9.14 Coronary artery aneurysms have been increasingly reported as a complication of DES.15 Aneurysm formation is a recognized complication of coronary artery stenting with bare-metal stents and of angioplasty without stenting.16 To some extent, these aneurysms are presumably due to inflation of the angioplasty balloon as a simple mechanical consequence of the procedure. That is, however, an unlikely explanation for aneurysms developing for months to years after DES placement. The drugs in these stents are immunosuppressants such as sirolimus, which inhibit inflammation, or chemotherapeutic agents such as paclitaxel, which inhibit cell proliferation and, in turn, inflammation. As long as the drug is eluting, hypersensitivity vasculitis is presumably inhibited, but once the drug has eluted, the polymer in which the drug is embedded may elicit a hypersensitivity reaction uninhibited by the drug. This concept is supported by the finding of an eosinophilic infiltrate in the few cases of such post-stent coronary artery aneurysms examined histologically.17 Connective tissue diseases such as Marfan syndrome can cause aneurysms without atherosclerosis. Marfan syndrome is associated with mutations in the gene for fibrillin (a major component of microfibrils associated with elastin fibers), and fibrillin is homologous with the family of latent transforming growth factor (TGF-β)-binding proteins, which hold TGF-β in an inactive complex.18 Other aneurysm syndromes have recently been JICC Vol 2 Number 2
NATURAL HISTORY OF GIANT CORONARY ANEURYSM Giant coronary aneurysms are rare, with an incidence of 0.02%. Li et al were the first to report their surgical experience with giant coronary aneurysms over an 8-year period.20 Because of the rarity of giant coronary aneurysms, the exact natural progression is unknown. It appears that all of them will develop complications at some point and will likely require surgical intervention. Patients are often asymptomatic when they are diagnosed with coronary aneurysms, but they may present with exercise-induced angina, unstable angina, and, occasionally, MI. Potential complications include thrombosis, embolism, rupture, fistula to the cardiac chambers, and endocarditis. Most giant coronary aneurysms reported in the medical literature have involved the RCA adjacent to the right atrium.20
MANAGEMENT There appears to be no significant difference in survival between patients who have aneurysmal or non-aneurysmal CAD when factors such as HTN, diabetes mellitus, lipid abnormalities, family history, cigarette smoking, MI, and peripheral vascular disease are examined. Given the frequency of thrombosis in coronary artery aneurysms, antiplatelet therapy (with aspirin or clopidogrel) or anticoagulation (with warfarin) has predictably been reported useful in the medical management of these aneurysms. Stenting and coil embolization have been used in the nonsurgical management of coronary aneurysms. It is unknown whether size alone is an indication for surgical 85
© 2012 ICC
Mishra, et al
5.
intervention. Some surgeons believe that surgical repair is mandatory when a coronary aneurysm is 3 times larger than the original vessel diameter. Other techniques have included reconstruction and direct repair via mobilization of the inflow and outflow portions and end-to-end anastomosis. Percutaneous management of giant aneurysms have also been advocated. This includes coil embolization, covered graft and stent graft implantation. The best strategy is that the treatment should be individualized in view of lack of randomized trials.
Mariana Díaz-Zamudio, UlisesBacilio-Pérez, Mary C. Herrera-Zarza, et al. Coronary artery aneurysms and ectasia: role of coronary CT angiography. RadioGraphics 2009;29:1939–54. 6. Kamiya T. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Annual Report of Research Committee on Kawasaki Disease. Tokyo: Japanese Ministry of Health and Welfare 1983:1–13. 7. Dajani AS, Taubert KA, Takahashi M, et al. Guidelines for long-term management of patients with Kawasaki disease: report from the Committee on rheumatic fever, endocarditis, and Kawasaki disease, Council on cardiovascular disease in the young, American Heart Association. Circulation 1994;89:916–22. 8. Falsetti HL, Carrol RJ. Coronary artery aneurysm: a review of the literature with a report of 11 new cases. Chest 1976;69:630–6. 9. Munkner T, Petersen O, Vesterdal J. Congenital aneurysm of the coronary artery with an arteriovenous fistula. Acta Radiol 1958;50: 333–40. 10. Cohen P, O’Gara PT. Coronary artery aneurysms: a review of the natural
CONCLUSION Coronary artery aneurysm is found in 0.3–5% of patients undergoing coronary angiography. Giant coronary aneurysms have been reported less frequently, with a reported frequency of 0.02%. Multivessel giant coronary aneurysms have been reported occasionally. Although, varied etiology have been described, atherosclerosis is the main cause comprising about 50% of the cases of coronary aneurysms. Other etiologies include congenital cases, inflammatory conditions like Kawasaki disease, Behchet syndrome, systemic lupus erythematosus, connective tissue disorders, and cocaine abuse. Drug-eluting stents implantation is also emerging as a significant cause. The exact pathogenesis has not been diagnosed as yet, but an inflammatory process is underlying in many such conditions. Symptoms, if present, are usually related to myocardial ischemia. Angiography is the mainstay for diagnosis. The prognosis is generally favorable. Thromboembolic complications are rare with antiplatelet therapy, and spontaneous rupture generally is rare but occurs more commonly in Kawasaki disease. Management varies from antithrombotic therapy to surgical ligation. Controlling coronary heart disease risk factors sharply affects the prognosis in patients with coronary artery aneurysm. ♦
11.
12. 13.
14.
15.
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