Coronary artery aneurysms (CAA) are characterized by abnormal dilatation of a localized or diffuse segment of the coronary arterial tree, up to 1.5 times the diameter of an adjacent normal segment.1 In Western populations, the incidence ranges between 1.5–4.9% and the most common association is with atherosclerotic coronary artery disease (CAD), which is considered the major cause of their formation.2 A congenital or inflammatory origin is found in 20–30% and 10–20% of cases, respectively.3 A high incidence (15–35%) of CAA has been reported in Japanese patients with Kawasaki’s disease.4

The role that CAA play in causing myocardial ischemia in an otherwise normal coronary arterial tree has been debated. Angina pectoris, silent myocardial ischemia and, occasionally, acute myocardial infarction have been reported in patients with CAA, even in the absence of underlying CAD.5 CAA repair has been recommended for those patients who are symptomatic or develop complications.6,7 We report a patient with a large CAA and no coexistent CAD, who developed myocardial infarction. This article describes the CAA clinical features, morphologic appearance as assessed by angiography and intravascular ultrasound (IVUS), and coronary flow dynamics studied with pulsed wave Doppler before and after successful obliteration with stent graft implantation.

Case Report.A 64-year-old white woman with a history of moderate hypertension and hypercholesterolemia was admitted to a different hospital 3 hours after sudden onset of severe prolonged chest pain. She had no personal or family history of CAD or other remarkable diseases. Electrocardiogram (ECG) revealed T-wave inversion in the precordial leads. Serum levels of creatine kinase (CK) and CK-MB rose to 407 U/L (normal, < 200 U/L) and 69 U/L (normal, < 20 U/L), respectively. An acute non-Q wave anteroseptal myocardial infarction was diagnosed and no thrombolytic therapy was administered. She had an uncomplicated hospital course and 1 month later was referred to our institution for further evaluation. On admission, physical examination and chest x-ray were normal. Laboratory tests showed no evidence of autoimmune or inflammatory diseases. Negative T-waves were still present in the ECG anterolateral leads. Left ventriculography showed an ejection fraction of 66% and mild anteroapical hypokinesis. Selective coronary angiography revealed a large, saccular-shaped aneurysm involving the proximal third of the left anterior descending artery (LAD) and no evidence of atherosclerotic disease of the entire coronary tree (Figure 1A). The first septal perforator branch was seen arising from the inferior wall of the aneurysm. The marked aneurysmal dilatation filled with contrast medium in a swirling fashion and had no evidence of thrombus formation. The opacification of the distal LAD was somewhat delayed.

The patient received 325 mg of aspirin, 250 mg of oral ticlopidine and 10,000 U of intravenous heparin. An 8 French (Fr) Extra Back-up guiding catheter (Cordis Corporation, Miami, Florida) was advanced to the left main ostium by way of a right femoral approach. A 0.014´´ guidewire was advanced into the distal LAD. This maneuver was accomplished with difficulty due to the large size of the CAA and to the fact that the CAA afferent and efferent LAD segments were asymmetrically located. A 30 Mhz, 3.2 Fr Ultracross IVUS catheter (Boston Scientific/Scimed, Inc., Maple Grove, Minnesota) was then advanced over the wire distal to the CAA. IVUS evaluation, performed after intracoronary nitroglycerin administration (250 µg) with automatic catheter pullback (0.5 mm/s), revealed an 18 mm long and 12.2 x 10.8 mm wide aneurysm (Figure 2A). The aneurysm showed no evidence of atherosclerosis, thrombus or calcification. Blood speckles suggesting slow flow were observed in its lumen. The presence of a continuous arterial wall layer across the area of dilatation indicated that the underlying pathology was that of a true aneurysm. The proximal and distal reference segments of the LAD were free of significant intimal thickening. Their lumen diameters measured 5.1 x 4.8 mm and 4.5 x 4.3 mm, respectively.
The guidewire was exchanged with a 0.014´´ Doppler FloWire (Cardiometrics, Inc., Mountain View, California) using a multifunctional probing catheter (Schneider AG, Bülach, Switzerland). The average peak velocity (APV) and diastolic to systolic velocity ratio (DSVR) were recorded 2 cm distal to the aneurysmal lesion. After baseline measurements were obtained, coronary flow reserve was evaluated with a bolus intracoronary injection of 18 µg of adenosine. The calculated coronary flow reserve (CFR) was significantly reduced (Figure 3A, Table 1).
The concept of a percutaneous intervention using a stent graft was explained to the patient, who accepted the nonsurgical treatment and gave written consent. A 26 mm long polytetrafluoroethylene (PTFE)-covered stent graft (JOSTENT, JOMED International AB, Helsingborg, Sweden) was hand-crimped onto a 4.0 x 30 mm Worldpass balloon catheter (Cordis Europe, LJ Roden, The Netherlands) and deployed across the aneurysm with a single inflation to 12 atmospheres (atm). A 5.0 x 20 mm noncompliant Tacker balloon catheter (Cordis Europe) was used to further postdilate the stent graft to 14 atm. Before inflation, the two end markers of the balloon were precisely aligned with the radioscopically well visible stent graft ends to avoid injury of the non-stented vessel. Repeat angiography revealed complete obliteration of the large aneurysm, occlusion of the small septal branch arising from it and marked improvement of distal LAD opacification (Figure 1B). Full stent graft expansion with apposition of the proximal and distal stent struts to the normal coronary wall and CAA exclusion were demonstrated by IVUS imaging (Figure 2B). The Doppler flow velocity tracing and parameters after stent graft deployment are shown in Figure 3B and Table 1. The postoperative course was uneventful and no rise of cardiac enzymes was observed. The patient was discharged 3 days after the procedure on aspirin (325 mg/day) indefinitely and ticlopidine (250 mg twice daily) maintained for 3 months.
After 7 months, the patient was free of symptoms and underwent repeat coronary angiography because SPECT Tc-MIBI myocardial scintigraphy revealed an exercise-induced anteroapical reversible defect. Permanent aneurysm exclusion and severe restenosis were demonstrated in the proximal third of the stent graft (Figure 1C). IVUS evidenced no change in the diameter of the stent graft and massive hyperplasia occupying the majority of its proximal lumen for a length of 8 mm (Figure 3C). Minimally invasive direct coronary bypass surgery with implantation of the left internal mammary artery to the LAD was decided in view of the underlying pathology and the lack of experience in the interventional treatment of covered stent restenosis. The patient was discharged after 4 days of uneventful postoperative course. She did well without symptoms over the following year.

Discussion. In this case, the etiology of the CAA could not be determined with certainty. Apart from moderate hypertension and hypercholesterolemia, both medically treated, there were no other risk factors for CAD. In addition, angiography and IVUS excluded coronary atherosclerosis in the aneurysmal and adjacent LAD wall. Furthermore, there was neither history suggesting Kawasaki’s disease nor laboratory evidence of collagen, infectious or inflammatory diseases. Finally, although a congenital origin could be inferred, this patient did not have arteriovenous fistula or other congenital abnormalities, which are often associated with this rare etiology.3
The CAA characteristics were studied with IVUS. This diagnostic technique was particularly useful to exclude underlying atherosclerosis and to determine CAA wall architecture, diameter and length (allowing the appropriate size of the stent graft to be selected) and to evaluate the adequacy of stent graft implantation. Interestingly, the CAA was not associated with atherosclerotic coronary lesions (a much less common condition compared to the coexistence of CAA and coronary obstruction)8 and was complicated by acute myocardial infarction. From a pathogenetic standpoint, CAA can cause stasis of blood, which in turn may promote in situ thrombosis with total lumen occlusion or distal embolization from mural thrombus.9–12 These flow alterations associated with thrombotic complications may have played a role in our patient, promoting myocardial ischemia and resulting in acute myocardial infarction. However, it is noteworthy that despite absence of coronary atherosclerosis, the Doppler flow study showed a marked reduction of CFR. The mechanism of this finding is not completely clear. Possible explanations could be a concomitant microcirculatory impairment13 or a CFR “pseudoreduction” due to the relatively high APV. The lack of a reference vessel CFR measurement makes it difficult to rule out the first hypothesis. However, diseases impairing microcirculation, such as diabetes, left ventricular hypertrophy or dilated cardiomyopathy, were excluded in our patient.
Moreover, the significant reduction of APV and the normalization of CFR after CAA obliteration suggest that high baseline flow velocity could be the more likely explanation. High baseline flow velocity could be the result of compensatory arteriolar vasodilation induced by flow reduction inside the aneurysm. Alternatively, the anatomical condition of this CAA (spherical, with the inlet and outlet asymmetrically located) may have induced a whirling flow inside the aneurysmal lumen with a persistent acceleration of the blood beyond it. From the available data, however, it is not possible to attribute a causative role to the altered CAA flow dynamics in the pathogenesis of the acute ischemic event.
Surgical treatment of CAA has been recommended for patients who develop symptoms or complications, but is still controversial.5–7 This is due to the lack of randomized data showing superiority of this strategy in comparison with medical therapy. The purpose of surgery, usually consisting of coronary artery bypass grafting and, if possible, aneurysm resection, is to prevent myocardial infarction, rupture or infection of the CAA. Endovascular techniques with newer interventional devices have been recently proposed in large and symptomatic CAA14 as an alternative to surgery. Spring coil embolization, although successfully used,15 may be complicated by parent vessel thrombosis or distal coil embolization. A novel and more appealing transcatheter technique uses composite endoluminal stent grafts to provide precise and effective aneurysm obliteration with preservation of lumen patency. Initially, autologous-vein coated stents were employed.16,17 This approach is limited by the large lumen (10 Fr) guiding catheter needed for delivery and the cumbersome and time-consuming stent-graft preparation, which includes surgical harvesting of a patient’s vein and accurate vein sewing to the stent ends. New stent grafts consisting of a thin elastic PTFE membrane integrated between two metal stents have been recently developed to overcome these limitations.18 These devices are currently under investigation for the percutaneous management of coronary artery rupture, aneurysm and fistula, and for the treatment of degenerated saphenous graft lesions or thrombus-containing lesions. In this patient, the previous myocardial infarction and the proximal LAD location of the CAA were the main reasons for our attempt to exclude the aneurysm with a PTFE-covered stent. Our acute result is consistent with the few cases in which the same device was successfully used to percutaneously obliterate CAA. However, in 2 out of the 3 previous reports, CAAs developed following PTCA or stenting and were smaller in size.19–21
Some concern has been created by other reports of late thrombo-occlusive events of PTFE-covered stents implanted for the treatment of occlusive coronary artery disease.18 Thrombus formation is likely due to delayed graft reendothelialization.22 Studies in a small number of patients have shown that prolonged antiplatelet therapy and high-pressure expansion of the stent graft monitored with IVUS may prevent thrombotic complications.23 However, further clinical experience is required to substantiate these observations. Severe in-stent graft restenosis was found at angiographic and IVUS follow-up in our patient, suggesting that exuberant tissue in-growth induced by the biomaterial may be another limitation. Experimental studies demonstrated that transmural endothelialization of PTFE grafts is minimal and that neointimal hyperplasia occurs mainly from the graft ends.24 These observations seem confirmed by the proximal location of the severe hyperplastic response observed in this case. Previous reports suggested that this could be due to the length of metallic struts not covered by the PTFE layer on each side of the Jomed stent graft.20 Since we used the newer generation of this device, which features nearly complete coverage of the stent, a direct interaction between the PTFE material and the vascular wall response could be inferred. Neointimal hyperplasia of coronary PTFE stent grafts may pose new problems for interventional treatment. Balloon angioplasty of in-stent graft restenosis could be limited by the inability to extrude the hyperplastic tissue through the PTFE membrane, while debulking techniques may carry the risk of graft material damage. These observations suggest that PTFE stent grafts can undoubtedly benefit from adjunctive technologies such as thrombo-resistant coatings25 and antiproliferative drugs delivered by the covering.26