Coronary Angiographic Morphology in Unstable Angina: Comparative Observations of Culprit Lesions in Saphenous Vein Grafts Versus

The acute coronary syndromes share a common pathogenetic mechanism involving plaque disruption, platelet activation and superimposed thrombus.1 Acutely ruptured plaques have a characteristic angiographic appearance directly reflecting mechanical disruption at the shoulder of the atherosclerotic plaque. Intracoronary thrombus is also commonly observed in patients with severe episodes of acute ischemia and is angiographically demonstrable with a higher incidence than in less acute presentations.2 The marked heterogeneity in patient characteristics and morphologic features directly reflects the wide spectrum of severity of ischemia and variability of clinical presentations.3 The occurrence of recent-onset chest pain with refractory and/or post-infarction angina is strongly associated with complex lesions, angiographically-detected thrombus and decreased TIMI flow.4 It is not widely appreciated that most prior studies of acute coronary syndromes exclude patients with prior coronary artery bypass surgery, primarily because it has been assumed that different disease extent, patient age, left ventricular function, and other clinical factors associated with increased risk5 would markedly influence the results. Consequently, no in-depth evaluation of the angiographic findings in patients presenting with unstable angina due to stenoses located in saphenous vein grafts, who represent an increasing population in cardiology practice, has been performed. Specifically, whether or not the mechanism of acute ischemic syndromes is the same in vein grafts has never been fully evaluated. Another aspect of the problem is that most acute coronary syndrome studies exclude patients with saphenous vein graft culprit lesions because of an inability to identify a single culprit lesion, given the multivessel nature of the underlying coronary disease. Prior morphologic analyses of culprit lesions also confine patient inclusion to patients with culprit lesions in the native coronaries since the Ambrose classification of lesion characterization6 has never been validated in vein grafts. The current study investigates lesion complexity in patients presenting with unstable angina due to culprit lesions in saphenous vein grafts and compares the morphologic and clinical characteristics to those of patients who present with culprit lesions in native coronary arteries. Specifically, the aim of this investigation was to determine if culprit lesion morphology and particularly the incidence of thrombus and ulcerated plaque as assessed angiographically differ between these two groups. METHODS Patient population. Over a 40-month period, a total of 445 consecutive patients admitted to Rush-Presbyterian-St. Luke’s Medical Center in Chicago, Illinois with a diagnosis of unstable angina who underwent cardiac catheterization and had subsequent coronary intervention during that hospital admission were included in the study. All patients admitted during this time frame with prior bypass surgery who presented with unstable angina and had an intervention performed were included. These selection criteria allowed inclusion of 90% of the total eligible cases. The purpose of making the performance of coronary intervention part of the inclusion criteria was to facilitate the identification of a single culprit lesion in patients with multivessel disease. Patients were identified using a prospectively collected computerized database in which clinical characteristics are entered into the database at the time of the procedure. The attending interventional cardiologist and the interventional fellow complete forms that are entered into a custom-designed Paradox-based database, compatible with the American College of Cardiology-National Cardiovascular Database Registry. The collected data include numerous additional clinical and morphologic characters developed on site.7,8 The definitions used follow those previously described by our group.7 Unstable angina is defined as angina occurring at rest or with decreased exertion, with increased frequency, or at new onset. All patients with electrocardiographic evidence of ST elevation of one or more millimeters in two or more contiguous leads or new Q-waves were excluded. Patients with evidence for acute myocardial infarction by elevation of CK-MB fraction (> 5.0%) or with elevated troponin I (> 1.0 mg/dl) were excluded. Clinical parameters. Numerous clinical characteristics were collected on all patients as previously described by our group.9 The Rush model is a previously validated clinical algorithm shown to be strongly predictive of acuteness of presentation and in-hospital outcome. It incorporates 6 clinical variables known at the time of clinical presentation, including recent myocardial infarction (Angiographic analysis. All 445 angiograms were reviewed for this study. Culprit lesions were identified by the presence of an angiographic stenosis >= 70%, ST-segment and T-wave changes in the corresponding anatomic location, and the occurrence of a matching regional wall motion abnormality as defined on left ventriculogram or same admission echocardiogram. Confirmation of the culprit lesion was sought in correlating the site of the coronary intervention and subsequent anginal relief. Single culprit lesions were identifiable in all cases, as this was determined using both clinical and angiographic parameters. In several patients, a thrombus was observed downstream from an ulcerated plaque, often itself containing residual thrombus. In such cases, the culprit lesion was classified as having demonstrated thrombus and an ulcerated plaque. Culprit lesions were categorized as being within saphenous vein grafts or native coronary arteries. All culprit lesions were categorized by the classification system defined by Ambrose.6 A concentric lesion was defined as a symmetric and smooth narrowing. An eccentric lesion was further characterized as having either smooth borders or irregular borders. Eccentric, irregular lesions are those described by Ambrose as eccentric type II lesions.6 These are recognized as convex intraluminal obstructions with a narrow base due to overhanging edges and irregular or scalloped borders. The presence of thrombus, assessed angiographically, was defined as an ovoid filling defect surrounded on at least three sides by contrast or, in a total occlusion, as a convex margin that remained contrast-stained for several cardiac cycles. Eccentric, irregular lesions were considered to be ulcerated plaque. When the criteria for a thrombus were fulfilled, a judgment was made whether both thrombus and ulceration were present, or only one. Total occlusion was defined as a lesion with TIMI grade 0 flow and no evidence of distal antegrade flow. Coronary angiographic morphology was interpreted by investigators blinded to the clinical parameters. In our laboratory, morphologic analysis has an intra-observer variability of Statistics. All continuous variables are expressed as means ± standard deviation. The student’s t-test was used for all continuous variables, and the Chi-square test was used to compare categorical variables. A p-value of RESULTS Of the 445 consecutive patients who underwent catheterization and percutaneous coronary intervention for unstable angina, culprit lesions were identified in saphenous vein grafts in 214 patients and within the native coronary arteries in 231 patients. Clinical characteristics. The saphenous vein graft group was found to have a male predominance (86.4% vs. 66.7%; p = 0.001) and were older than the native coronary group (67 ± 9 years vs. 64 ± 12 years, respectively; p = 0.0017). There was a trend toward lower left ventricular ejection fraction in the patients within the saphenous vein graft group (54 ± 16% vs. 58 ± 15% in the native coronary group; p = 0.063). Angiographic findings (Figure 1). There was a higher incidence of angiographically identifiable thrombus in saphenous vein graft lesions as compared to native coronary artery lesions. Using the pre-specified definition, a total of 67/214 (31.3%) saphenous vein graft lesions had angiographic evidence of thrombus, while only 15/231 (6.5%) native coronary artery lesions had thrombus (p = 0.001; Figure 1). There was also a higher incidence of ulcerated plaque in saphenous vein graft lesions: 79/214 culprit lesions in vein grafts (36.9%) versus 51/231 in native coronary artery lesions (22.1%; p = 0.001). Total occlusions were infrequent overall in the culprit vessel, as would be expected in a patient population presenting with unstable angina, rather than Q-wave myocardial infarction. Culprit lesions within the saphenous vein graft group were identified as total occlusions in only 7.9% as compared to 13.0% in the native coronary artery group. This did not reach statistical significance (p = 0.084), but a trend was suggested. In addition, all patients with total occlusions had angiographic evidence of collaterals, and thus collaterals also tended to be more frequent in the native coronary group. The Rush model. The Rush model,9 which is predictive of in-hospital outcomes in unstable angina and based on the Braunwald criteria,5 was evaluated for its capability to predict the presence of thrombus, ulceration and culprit lesion location in a native vessel or vein graft. The Rush score was strongly predictive of the presence of an Ambrose type II culprit stenosis in the entire 445 patient cohort (p Multivariate analysis. Multivariate analysis was performed using the variables that were significant by univariate analysis. The most discriminating angiographic variable was the incidence of thrombus, which was far more common in saphenous vein graft lesions than in native coronary lesions [p = 0.001; odds ratio (OR), 6.0; 95% confidence interval (CI), 3.2–11.4]. Ulcerated plaque was also highly correlated with saphenous vein graft culprit lesions as compared to native coronary lesions (p = 0.0086; OR, 1.9; 95% CI, 1.2–3.0). Clinical characteristics associated with vein graft culprit lesions included baseline ST-segment depression (p DISCUSSION This study demonstrates that Ambrose eccentric type II lesions, the angiographic morphology reflective of ulcerated plaque and thrombus, are more commonly observed in culprit lesions occurring in saphenous vein grafts than in culprit lesions within native coronary arteries, while total occlusions with collaterals are more common in native coronaries. Active thrombotic and ulcerated lesions underlie acute ischemic syndromes more commonly in saphenous vein grafts than in native vessels, and the presence of these angiographic morphologies is associated with a higher clinical score predictive of increased in-hospital complications.5,9 There are several clinically important implications of the finding that Ambrose eccentric type II lesions are more commonly observed in culprit lesions in vein grafts than in native coronary lesions. The higher incidence of thrombus and plaque rupture in these cases suggests either a more rapidly progressive pathophysiologic process10 or a more thrombotic milieu. Culprit saphenous vein graft lesions may also be more likely to contain thrombus because diffuse atherosclerosis is uncommon, whereas friable, thrombotic lesions are frequently observed.11 The current data cannot define which of these factors, or combination of factors, is the best explanation. Diminished endothelialization and the presence of grumous-like material within older vein grafts11 are the origins of the pathophysiologic link between the clinical presentation and these angiographic findings. An additional factor to consider is that the larger lumen size and relative lack of diffuse atherosclerotic disease may allow more precise angiographic recognition than in native vessels, resulting in the enhanced predictive value of the Ambrose characterization in this patient subgroup. Another consideration is that the larger thrombus burden in vein grafts may not be due to the plaque itself, but instead a consequence of slow flow within a larger luminal volume, resulting in a bigger thrombus that is more easily identified angiographically. However, this study strongly suggests that active thrombotic lesions, either superimposed on a ruptured plaque or originating on the wall of the graft, cause ischemia more frequently in saphenous vein grafts than in native coronary arteries. These results are important because they demonstrate that acute coronary syndromes produced by culprit lesions in saphenous vein grafts have a high incidence of angiographic stenosis morphology consistent with thrombosis or plaque rupture, suggesting the possibility of a more rapidly progressive pathophysiologic milieu than in native coronaries. This likely translates into the more frequent clinical complication rate often observed in this patient group.12,13 The higher rate of distal microembolization in these cases is also explained, in part, on this basis. This inter-relationship between adverse lesion morphology, clinical presentation and high clinical risk is remarkably redolent to that described in non-Q wave infarction.7,14 Understanding that unstable angina due to culprit lesions in native coronaries compared to saphenous vein grafts has somewhat different clinical, angiographic and pathophysiologic characteristics may lead to improved therapy of these patients. Three of the individual criteria contained in the Rush model distinguished the location of the culprit lesion as native coronary artery or vein graft, although the total Rush score was not discerning in this regard. It is well recognized that patients with acute coronary syndromes who have had bypass surgery have a worse outcome,12,13 and this study found an association between several clinical parameters predictive of increased risk and vein graft culprit lesions. Patients with saphenous vein graft culprit lesions are older, diabetic, have more ST depression on the baseline ECG, and have a lower ejection fraction than patients with culprit lesions within native coronary arteries. Dangas and colleagues4 have shown that the Braunwald classification is a powerful independent predictor of complex lesion morphology in native coronaries in patients with refractory angina. They suggested that the use of this classification could facilitate triage and selection of patients for more aggressive care. The current study suggests an important caveat to this observation. Although the Rush model was predictive of Ambrose type II culprit lesions, there was no difference as to whether the culprit lesion was in a vein graft or native vessel. Thus, while acuteness of presentation and in-hospital risk are generally reflected by lesion morphology, regardless of the culprit vessel, it is the clinical presentation of a particular patient which defines risk. This conclusion is reflected by the absence of a difference between the groups in this study regarding the components of the model most strongly predictive of acuity of presentation and in-hospital risk, specifically recent myocardial infarction (CONCLUSION This study analyzes and compares the coronary angiographic findings in unstable angina produced by culprit lesions in native coronary arteries and vein grafts for the first time. Thrombus and ulceration are present more frequently in vein graft culprit lesions, which may be a function of different pathophysiology, clinical risk, disease extent, angiographic recognition, treatment effects or a combination of these. These data are important to an improved comprehension of the etiology of acute ischemic syndromes in an increasing segment of the patient population (i.e., post-coronary bypass) that is usually excluded from acute ischemic syndrome studies.

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