Predictive Value of the Angiographic Anatomic Characteristics of the Left Main Coronary on Acute Myocardial Infarction in Patients With Coronary Atherosclerosis

Abstract: Background. The coronary artery anatomic morphology is a critical determining factor for intracoronary hemodynamics and atherosclerotic lesion formation. This study aimed to test whether the anatomic characteristics of the left main (LM) coronary artery can predict acute myocardial infarction in the left coronary artery (AMI-LC). Methods. We retrospectively analyzed the clinical and coronary angiographic data of 1825 consecutive patients who underwent coronary angiography. Among them, 149 presented with AMI-LC, and 1118 had coronary artery stenosis >50%, but were without complete coronary occlusion. The length and diameter of the LM and the angle between the left anterior descending (LAD) or circumflex artery and the LM were determined by quantitative coronary angiography. Results. The AMI-LC patients had a shorter LM length (11.6 ± 2.1 mm, 14.3 ± 1.9 mm, and 15.8 ± 5.9 mm, respectively; P<.001) and a larger angle between the LAD and the LM (127 ± 27°, 115 ± 29°, and 119 ± 32°, respectively; P<.001) than the coronary artery disease (CAD) patients without complete coronary occlusion and normal subjects. The patients were divided into short-LM (3.65-10.95 mm), medium-LM (10.96-15.24 mm), and long-LM (15.25-37.84 mm) groups based on the length of the LM. The incidence of AMI-LC in the short-LM group was significantly higher than in the other two groups (14.4%, 7.4%, and 4.2%, respectively; P=.001). Multiple logistic regression analysis showed that LM length and the angle between the LAD and the LM were independent predictors of the occurrence of AMI-LC. The receiver operating characteristic curve test showed that their combination can predict AMI-LC with a sensitivity of 72% and a specificity of 86%. Conclusion. Short LM length and a large angle between the LAD and LM may be independent risk factors for AMI-LC in CAD patients.

J INVASIVE CARDIOL 2013;25(9):449-454

Key words: acute myocardial infarction, coronary angiography,left main, vascular morphology, hemodynamics 

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Typically, acute myocardial infarction (AMI) is due to the rupture of a “vulnerable atherosclerotic plaque.” The degree of vascular stenosis, as an index of coronary atherosclerotic lesion severity, has been shown to have a poor correlation with plaque vulnerability.^1-4 Most “criminal plaques” commonly occur in vessels with lumen narrowing of <70%, and choosing a treatment strategy is difficult. Because an atherosclerotic plaque within the vascular cavity is always under a certain mechanical load derived from the blood pressure and flow, plaque rupture is prone to occur when the increased extra load exceeds the material strength of the plaque fibrotic cap.^5,6 Therefore, both the vascular morphological and local mechanical features of a lesion should be considered in the assessment of the vulnerability of a lesion plaque and the identification of at-risk patients.^7-9

Generally, the left main (LM) coronary arises from the aorta and then bifurcates into the left anterior descending (LAD) artery and the left circumflex (LCX) artery. From a histological viewpoint, the LM is a rather peculiar muscular artery, since it originates directly from the aortic wall and lacks the tunica adventitia at the ostium. The tunica media of the LM is extremely rich in smooth muscle cells and elastic tissue. The elastic component in the LM is more abundant than in any other coronary branch and tends to decrease distally toward the LM.¹⁰ Logically, the specific anatomic features of the LM should enable it to buffer the coronary blood flow from the aorta and alleviate long-term flow-force induced vascular injuries in its downstream branches.¹¹ Indeed, Gazetopoulos reported that the length of the LM might be associated with the increased incidence and severity of atherosclerosis.¹² Rodriguez-Granillo also demonstrated that the angle of bifurcation of the LM acted as a predictor of atherosclerotic plaques in the proximal branch vessels by CT angiography.¹³ Therefore, based on the potential relationship between the blood flow force from the upstream vessel and the formation of vulnerable atherosclerotic plaques in the downstream branches, this study tested whether the anatomic characteristics of the LM were associated with the occurrence of AMI in the left coronary artery (AMI-LC), including the LAD and the LCX, by retrospectively analyzing the data from 1825 consecutive inpatients who underwent coronary angiography in our hospital.

Methods

Patient selection. From June to December in 2010, a total of 1825 subjects underwent coronary angiography in the Department of Cardiology of Shanghai Sixth People’s Hospital and were enrolled in the study. The study was approved by the ethics committee of our hospital. The patient demographic information, clinical status, and laboratory tests were recorded, including age, gender, history of hypertension and diabetes, serum lipid levels, renal function, family history, intraoperative blood pressure, and heart rate. The coronary angiography data included the length and diameter of the LM and the angle between the LAD or LCX and the LM. Patients with incomplete clinical data, an abnormal origin of the coronary artery, unclear angiographic imaging, or LM atherosclerosis were excluded. 

The inclusion criteria for AMI were as follows: (1) TIMI flow grade 0-1, confirmed by coronary angiography; and (2) a history of definite AMI within 1 month, including dynamic changes on electrocardiogram, cardiac enzymes, and typical symptoms. In addition, patients with stent thrombosis were excluded. 

Quantitative analysis of angiographic anatomic characteristics of LM. All subjects received an intracoronary injection of 200 µg of nitroglycerin before the angiography procedure. The length, diameter, and angles between the LM and LAD (Angle LM/LAD) and LCX (Angle LM/LCX) were measured using a quantitative coronary analysis (QCA; Terra, GE) by two experienced interventional cardiologists who were unaware of the patients’ clinical statuses. For each parameter, three values were measured at three different end-diastolic frames, and the mean value was then calculated. The length of the LM was calculated by the following formula, which utilized the principles of trigonometry as in the study of Gazetopoulos et al:¹² length of LM (Length) = (1.072a² + 1.072b² + 0.555ab)^1/2, in which “a” and “b” are the projection lengths of the LM measured with QCA in left anterior oblique (LAO) 45° and right anterior oblique (RAO) 30°, respectively, on the plane of caudal (CAU) 30°. The vascular diameter, Angle LM/LAD, and Angle LM/LCX were measured in the LAO 45° on the plane of CAU 30°. The LM diameter was measured at the midpoint of the LM’s long axis. Additionally, the product of the LM length and diameter (Product) and the ratio of the diameter/length (Ratio) were calculated. 

The corrected TIMI frame count (CTFC) and the angiographic characteristics of the LM were evaluated in 200 males with negative coronary angiography who were without hypertension, diabetes, or other organic heart disease.

Statistical analysis. The analyses were performed using SPSS 13.0 (SPSS, Inc). Continuous data were presented as the median or mean ± standard error. Multiple comparisons were performed using the Kruskal-Wallis test or analysis of variance, as appropriate. The Spearman correlation coefficient was computed to examine the association between two continuous variables. The effects of different variables on AMI-LC were evaluated by multivariate analysis. A P<.05 was considered statistically significant. 

Results

Baseline characteristics. A total of 1825 consecutive cases with a mean age of 63.6 ± 10.4 years were enrolled in the study. Among them, 357 subjects had normal coronary angiography findings, 7 cases experienced acute in-stent thrombosis in the left coronary artery, and 149 cases presented with AMI-LC. Among the AMI-LC patients, 99 occurred in the LAD, 46 occurred in the LCX, and 4 occurred in both the LAD and LCX. In addition, 37 AMIs occurred in the right coronary artery (RCA), and 102 had chronic total obstructions in the left coronary, 55 of the chronic coronary total obstructions were present in the RCA (including 6 total stent obstructions). Coronary artery stenosis >50% without complete coronary occlusion (no-CCO CAD) was observed in 1118 patients. Table 1 shows the baseline clinical data for the normal coronary angiography, no-CCO CAD, and AMI-LC patients. The AMI-LC patients were more likely to be male and young to have higher serum levels of total cholesterol and low-density lipoproteins compared to the no-CCO CAD patients (P<.05). 

The relationship between the LM length and the CTFC on coronary angiography. The CTFC value on coronary angiography at least partially reflects the flow and speed of the downstream coronary circulation. First, to address the potential influence of LM anatomic characteristics on the hemodynamics of the left coronary branches, we randomly selected the data from 200 male subjects with normal coronary angiography results for analysis. We showed that the LM length was positively correlated with the CTFC (r = 0.382; P<.001). In contrast, the other indices, including the LM diameter, intraoperative blood pressure, and heart rate had no significant correlation with the CTFC, suggesting that LM length may be a key determining factor of the flow velocity of downstream branch circulation.

The angiographic morphologic features of the LM in AMI-LC patients. The QCA analysis showed that the AMI-LC patients had a higher proportion of non-dominant RCA than the no-CCO CAD subjects (13.1% vs 8.6%; P<.05). Furthermore, the length and diameter of the LM and their product in the AMI-LC group were significantly smaller than those in the normal control group (all P<.05). In contrast, the ratio of the diameter/length of the LM and the Angle LM/LAD in the AMI-LC group were significantly increased compared with those values in the no-CCO CAD group (all P<.05; Figure 1). 

All CAD patients, except for CTO patients, were divided into three groups based on their LM length: the short-LM group (8.70 mm; range, 3.65-10.95 mm), the medium-LM group (13.01 mm; range, 10.96-15.24 mm), and the long-LM group (20.08 mm; range, 15.25-37.84 mm). Each group was composed of 424 or 425 patients. The patients in the long-LM group were more likely to have a higher Product and lower Ratio than the patients in the medium-LM and short-LM groups (P<.05). However, there were no significant differences in the above-mentioned demographic and clinical characteristics among the three groups (Supplemental Table 1; see www.invasivecardiology.com). For all consecutive patients, the incidence of AMI-LC in the short-LM group was significantly higher compared to the medium-LM and long-LM groups (14.4% vs 7.4% and 4.2%, respectively; P=.001; Figure 2A). As previously reported,¹³ we also found that AMI-LC was prone to occur in the proximal LAD or LCX compared with the middle and distal regions (93 vs 45 and 11, respectively; P<.001). However, the percentage of middle and distal criminal lesions in the short-LM group (46.6%) was higher than in the medium-LM group (30.2%) and long-LM group (12.5%; P=.000). Therefore, the total proportion of middle and distal AMIs decreased as the length of the LM increased (Figure 2B; P<.001). 

Predictors of AMI-LC. In the multivariate analysis, the stepwise logistic regression analysis showed that traditional risks, including age, male gender, and total cholesterol level, were independent predictors of AMI-LC. We also found that the non-dominant RCA was associated with AMI-LC (Table 2). Furthermore, the Angle LM/LAD was positively associated with AMI-LC, and LM length was negatively associated with AMI-LC. To increase the statistical power, continuous variables were redefined as dichotomous variables using the following cut-off values determined by the ROC curve or Youden index: Angle LM/LAD of 130°, Product of 87, and Ratio of 0.53. Meanwhile, the cut-off value of Length was 10.95, which was determined by tertiles. This model showed that Length, Product, Ratio, and Angle LM/LAD were independently associated with an increased risk of AMI-LC (Table 2). Next, we used ROC curves to explore the relationships among LM length, Angle LM/LAD, and AMI-LC. As shown in Figure 3, the area under the ROC curves for Length alone and Angle LM/LAD alone were 0.71 (95% confidence interval [CI], 0.65-0.78; P<.001) and 0.71 (95% CI, 0.65-0.76; P<.001), respectively. The area under the ROC curve for the combination of Length and Angle LM/LAD was 0.85 (95% CI, 0.82-0.88; P<.001). The model for AMI-LC was logit (p) = -1.970 + 0.048 × Angle LM/LAD – 0.469 × Length. The ROC test showed that when P=.238, the predictive sensitivity was increased to 72% and the specificity increased to 86% for AMI-LC. 

Interestingly, with the exception of the Angle LM/LAD, the other clinical characteristics were not significantly different between patients with AMI-LC in the LAD and those with AMI-LC in the LCX (Supplemental Table 2; see www.invasivecardiology.com). The multivariate regression analysis showed that an Angle LM/LAD >130° only predicted AMI in the LAD, not AMI in the LCX (Table 3). 

Discussion

In the present study, we demonstrated that LM length and the angle between the LM and LAD may be two powerful and independent predictors of AMI-LC in patients with coronary atherosclerosis. A short LM and large Angle LM/LAD were associated with a higher risk for AMI-LC, and logit (p) = 0.238 had 72% sensitivity and 86% specificity. 

Clinical studies have shown that more than 90% of “criminal plaques” commonly occur in vessels with <70% lumen narrowing. At present, most methods to evaluate plaque vulnerability have focused on the evaluation of the local plaque distribution, burden, and morphological characteristics as well as vascular remodeling, including spotty calcium and macrocalcifications at the fibrous cap, by multi-slice computed tomography (CT) angiography, intravascular ultrasonography, and other methods.^14-19 

However, whether and how the anatomic characteristics upstream influence plaque rupture has been less studied. Hemodynamic features appear to be one important risk factor for plaque rupture.^6-8 Of those, shear stress is the most frequently mentioned. Shear stress is the tangential force of the flowing blood on the endothelial surface of the blood vessel. Meanwhile, wall shear stress expresses the force per unit area exerted by the wall on the fluid in a direction on the local tangent plane.^20,21 The involvement of shear stress in atherosclerotic plaque rupture has been clearly shown to occur via two distinct mechanisms: low wall shear stress, which promotes the transition of the plaque from a stable lesion to a thin cap fibroatheroma and facilitates the formation of a vulnerable plaque,^22-27 and high shear stress, which contributes to the formation of atherosclerotic plaque fissure and rupture.^28-35 

According to Poiseuille’s law, both the blood flow rate and velocity are positively correlated with the vascular radius and negatively correlated with the vascular length.^36,37 For coronary circulation, angiographic CTFC, as a simple, more objective continuous variable index of coronary blood flow,^38,39 has been shown to have a good negative correlation with blood flow and distal average peak velocity.⁴⁰ In patients with normal coronary angiography, we observed that the LM length had a positive correlation with the CTFC, suggesting that a short LM can lead to an increase in the distal blood flow velocity. Therefore, understanding why both the vascular diameter and LM length can determine the amount of shear stress in the downstream vessels is not difficult. In this study, we demonstrated that the short-LM group had a higher incidence of AMI-LC than the medium-LM and long-LM groups. The multivariate regression analysis further showed that both the LM length and its derived variables (ie, the Product and Ratio) were independently associated with an increased risk of AMI-LC, suggesting that patients with a short LM have a higher risk of AMI-LC occurrence than those with a medium or long LM. Consistent with our results, Gazetopoulos et al reported that the LM length was significantly shorter in patients with coronary atherosclerosis than in subjects without angiographic evidence of CAD.¹² Notably, Cademartiri et al recently utilized 64-multidetector-row CT coronary angiography to assess the relationship between the LM dimensions and the presence of atherosclerosis. They found that the presence of atherosclerosis in the LM was correlated with vessel length and diameter. In particular, the diameters at the ostium and the bifurcation of the LM were significantly increased in patients with atherosclerotic plaques compared with those in patients without plaques. In addition, a moderate correlation was found between the LM diameter at the bifurcation and the corresponding plaque area in patients with plaques at the bifurcation.⁴¹ Collectively, these results suggested that LM anatomic characteristics play a role in the formation of atherosclerotic lesions. 

Additionally, AMI is well known to occur most often at the proximal segment of the LAD/LCX, not the middle or distal segments. Interestingly, we found that the short-LM group had a relatively higher incidence of middle and distal AMI-LC compared to the medium- and long-LM groups. Valgimigli et al also reported that plaques with a large necrotic core tended to be found more often in the distal tract of the LM than the proximal tract using intravascular ultrasound.⁴² Therefore, LM length appears to influence the distribution of “vulnerable plaques” along the coronary arteries. Although the underlying mechanism remains unclear, we presently consider that short-LM patients have a slower drop in the intracoronary pressure and blood velocity gradient compared to medium- and long-LM patients, thereby leading to a relatively higher shear stress in the middle and distal segments of the LAD/LCX, which may trigger plaque rupture. 

Several previous studies have demonstrated that the branching angle in coronary artery bifurcations is one important determinant of atherogenesis because it has the potential to change the local hemodynamic parameters, including wall shear stress and pulsatile flow waveform.^43-45 Additionally, a higher Angle LM/LAD was more likely to promote downstream vascular injuries under the conditions of higher wall shear stress and flow velocity waveforms.^44,45 Rodriguez-Granillo et al demonstrated that the angle of the left bifurcation might have an effect on shear stress and consequently on plaque size.¹³ Consistent with this correlation, we also demonstrated that the angle between the LM and LAD in AMI-LC patients was larger than in the no-CCO CAD patients. 

However, the Angle LM/LAD only predicted AMI in the LAD, not the LCX. Previous studies have shown that an increased angle of bifurcation of the daughter vessels induces not only a decrease in wall shear stress and an increase in the oscillatory shear index in the carina of the daughter vessels, but also a stronger oscillatory flow velocity in the direction perpendicular to the centerline of the mother vessel.^46-49 Certainly, the increased angle of bifurcation of the daughter vessels after the LM suggests decreases in the Angle LM/LAD and the Angle LM/LCX. In our study, the LCX was shown to be more perpendicular to the LM than the LAD in AMI-LC by coronary angiography, similar to a study by Kawasaki et al.⁵⁰ Therefore, with the increase in the Angle LM/LAD, the wall shear stress of the daughter vessels might be increased and thus was more likely to induce plaque rupture in the LAD than the LCX.

Collectively, our present study may provide a simple method to predict acute coronary events in the left coronary artery by analyzing the special LM angiographic morphological features in patients with CAD. Patients with special angiographic anatomic characteristics should receive more active and intensive therapeutic interventions. For example, it is always difficult to select an appropriate treatment strategy for critical lesions, in which the lumen is narrowed by 40%-70%. Lesions should be more prone to respond to percutaneous coronary intervention or coronary artery bypass grafting if they have a short LM and a larger Angle LM/LAD. Meanwhile, this study indicated that wall shear stress, followed by an analysis of the biomechanical risk factors, may be used as an additional diagnostic tool for clinicians to estimate plaque vulnerability and determine the proper treatment and intervention. Risk factors that would induce a higher blood velocity and flow rate, such as high blood pressure and excessive tension and strain, should be more effectively controlled.

Study limitations. Our study has several limitations. This study was conducted on a retrospective basis and represents a single-center experience with a relatively small sample. The measurement of the LM was based on visual inspections, not more quantitative measurements, such as intravascular ultrasound. Additionally, the value of the diameter or other measurements would have been affected if the course of the LM was not very close to CAU 30° or if vessel with spasm or expansion due to the disease was present. 

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