Hon-Kan Yip, MD; Chiung-Jen Wu, MD; Morgan Fu, MD; Kuo-Ho Yeh, MD; Teng-Hung Yu, MD; Wei-Chin Hung, MD; and Mien-Cheng Chen, MD

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1 Clinical Features and Outcome of Patients With Direct Percutaneous Coronary Intervention for Acute Myocardial Infarction Resulting From Left Circumflex Artery Occlusion* Hon-Kan Yip, MD; Chiung-Jen Wu, MD; Morgan Fu, MD; Kuo-Ho Yeh, MD; Teng-Hung Yu, MD; Wei-Chin Hung, MD; and Mien-Cheng Chen, MD Background: Little is known about the clinical features and outcome of patients with left circumflex artery (LCX) infarct-related acute myocardial infarction (AMI). This study was conducted to investigate the clinical features and outcome of patients who underwent direct percutaneous coronary intervention (d-pci) for AMI caused by LCX occlusion, and to discover prognostic determinants in this clinical setting. Methods and results: Between May 1993 and October 2000, a total of 819 patients with AMI underwent d-pci in our hospital. Sixty-seven patients (8.2%) who had LCX infarct-related AMI constituted the population of this study. Ten of 67 patients (14.9%) were in cardiogenic shock. Angiographic findings demonstrated that the incidences of triple-vessel disease, reference lumen diameter (RLD) of the LCX > 4.0 mm, and LCX as the dominant artery in these patients were 26.9%, 22.4%, and 34.3%, respectively. Sixteen patients (23.9%) had unsuccessful reperfusion (defined as Thrombolysis in Myocardial Infarction flow < 2). Univariate analysis showed that dominant LCX, RLD of the LCX > 4.0 mm, cardiogenic shock, precordial ST-segment depression, and complete atrioventricular block were significantly related to unsuccessful reperfusion. Multiple stepwise logistic regression analysis demonstrated that dominant LCX and cardiogenic shock were significant independent predictors of unsuccessful reperfusion. The 30-day mortality rate in the 67 patients was 14.9%. Univariate analysis demonstrated that triple-vessel disease, dominant LCX, cardiogenic shock, poor left ventricular ejection fraction, and unsuccessful reperfusion were significantly associated with 30-day mortality. By multiple stepwise logistic regression analysis, dominant LCX, cardiogenic shock, and triple-vessel disease were significant independent predictors of increased 30-day mortality. Conclusions: LCX infarct-related AMI has its unique clinical features. The presence of dominant LCX and cardiogenic shock were independent determinants of unsuccessful reperfusion, and the presence of dominant LCX, cardiogenic shock, and triple-vessel disease were independent determinants of increased 30-day mortality in this clinical setting. (CHEST 2002; 122: ) Key words: acute myocardial infarction; left circumflex occlusion; percutaneous coronary intervention Abbreviations: AMI acute myocardial infarction; CPK creatine phosphokinase; d-pci direct percutaneous coronary intervention; LAD left anterior descending artery; LCX left circumflex artery; MI myocardial infarction; RCA right coronary artery; PDA posterior descending artery; PLA posterolateral artery; RLD reference lumen diameter; TIMI Thrombolysis in Myocardial Infarction The incidence of left circumflex artery (LCX) infarct-related acute myocardial infarction (AMI) is lower than either right coronary artery (RCA) or left anterior descending artery (LAD) *From the Division of Cardiology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC. Manuscript received November 26, 2001; revision accepted May 7, Correspondence to: Mien-Cheng Chen, MD, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung Hsien, 83301, Taiwan, ROC; chenmien@ kinghenry.com.tw. infarct-related AMI. It usually accounts for 13.6 to 20.8% of AMIs. 1 3 Inferior wall myocardial infarction (MI) caused by occlusion of the RCA accounts for 40 to 50% of AMIs, 1 6 and is generally believed to have a more favorable outcome than anterior wall MI. 4 7 However, little is known about the clinical features and outcome of patients with LCX infarctrelated AMI, either due to the relative lower incidence of occurrence, or because it is subjectively viewed as having the most favorable clinical outcome. In addition, the anatomic features of the LCX and the prognostic determinants in this clinical 2068 Clinical Investigations

2 setting have not been discussed. Therefore, the purpose of this study was to investigate the clinical features and outcome of patients who underwent direct percutaneous coronary intervention (d-pci) for LCX infarct-related AMI, and to discover prognostic determinants in this clinical setting. Patient Population Materials and Methods In our hospital, all patients with AMI underwent d-pci after informed consent was obtained. For the purpose of study, all patients undergoing d-pci were prospectively identified and entered into a computerized database. Between May 1993 and October 2000, d-pci was performed in 838 patients of all ages who presented with AMI of 12-h duration (or cardiogenic shock within 18 h) in our hospital. Sixty-seven of 819 patients (8.2%) [excluding 19 patients with acute left main coronary artery occlusion] who had LCX infarct-related AMI constituted the population of this study. Procedure and Protocol The procedure and protocol have been described previously in detail. 8,9 Before stents were available in our country, primary balloon angioplasty was performed in these patients; however, after stents were available in our country, primary stenting was considered first for these patients and the stent type was selected at the discretion of the operators. Patients were treated with ticlopidine for 2 weeks if stenting was performed. Aspirin, 100 mg po qd, was administered to each patient indefinitely. There was no in-stent subacute thrombosis in this study population. Definitions Standard 12-lead ECGs were performed in all patients. AMI was defined as the following: (1) typical chest pain lasting for 30 min with ST-segment elevation 1 mm in two consecutive precordial or inferior leads; (2) typical chest pain lasting for 30 min with a new onset of complete left bundle branch block; or (3) typical chest pain lasting for 30 min with ST-segment depression 1 mm or definite T-wave inversion or both and an elevation of creatine phosphokinase (CPK) with creatine kinase-mb fraction 4% on at least one occasion. Precordial ST-segment depression was defined as 1 mm ST-segment depression in two consecutive precordial leads and measured 80 ms after the J point with reference to the PR segment. Posterior wall MI was defined as R/S ratio of 1 in lead V 1 or V 2. The LCX was considered dominant when both the posterior descending artery (PDA) and posterolateral artery (PLA) arose from the LCX and the RCA was very small size and did not supply any part of the left ventricle. The LCX was considered co-dominant when either the PDA or PLA arose from the LCX. The LCX was considered nondominant LCX when neither the PDA nor PLA arose from the LCX. Reperfusion time was defined as the time from symptom onset of chest pain to first balloon inflation. Procedural success was defined as a reduction to residual stenosis of 50% by balloon angioplasty or successful stent deployment at the desired position with a residual stenosis 30% followed by Thrombolysis in Myocardial Infarction (TIMI) 10 grade 3 flow in the LCX. Unsuccessful reperfusion was defined as TIMI grade 2 flow in the distal LCX in the absence of an occlusion at the treatment site or evidence of distal embolization. Data Collection Detailed in-hospital and follow-up data which included age, sex, coronary risk factors, Killip score on admission, reperfusion time, pre- and post-timi flow grades, angiographic results, number of diseased vessels (diseased vessel was defined as 50% of stenosis), and in-hospital adverse events were obtained. These data were collected prospectively and entered into a computerized database. Statistical Analysis Data were expressed by mean SD. Continuous variables were compared using Student t test or Wilcoxon rank test. Categorical variables were compared using 2 or the Fisher exact test. Stepwise logistic regression analysis was used to determine independent predictors of unsuccessful reperfusion and 30-day mortality. All statistical analyses were performed by using software (SAS for Windows, version 6.12; SAS Institute; Cary, NC). A p value 0.05 was considered as statistically significant. Results Comparison of Baseline Characteristics, Clinical Features, Angiographic Results, and 30-Day Mortality Relevant patient characteristics, angiographic results, and 30-day mortality among 819 patients with AMI resulting from different coronary artery occlusions are summarized in Table 1. Angiographic findings demonstrated that there was no significant difference in the number of diseased vessels between patients with LCX infarct-related AMIs and patients with LAD infarct-related AMIs (p 0.69). However, patients with LCX infarct-related AMIs had a significantly higher incidence of single-vessel disease and lower incidence of multivessel disease than patients with RCA infarct-related AMIs (p 0.008). Furthermore, angiographic results demonstrated that there was no significant difference in unsuccessful or successful reperfusion between patients with LCX infarct-related AMIs and patients with RCA infarct-related AMIs (p 0.23). However, patients with LCX infarct-related AMIs had a significantly lower incidence of successful reperfusion and higher incidence of unsuccessful reperfusion than patients with LAD infarct-related AMIs (p 0.011). There was no significant difference in 30-day overall mortality among patients of the three groups. After excluding 15 patients who had either infarct-related mechanical complications, or left main disease and multivessel disease and required either urgent or emergency surgical intervention after d-pci, there was also no significant difference in 30-day mortality among patients of the three groups. CHEST / 122 / 6/ DECEMBER,

3 Table 1 Comparison of Baseline Characteristics, Clinical Features, Angiographic Results, and 30-Day Mortality of 819 Patients With Different Infarct-Related Arteries* Variables LCX (n 67) RCA (n 291) LAD (n 461) p Value Age, yr Female gender 6 (9.0) 46 (15.8) 66 (14.3) 0.35 Hypertension 27 (40.3) 142 (48.8) 227 (49.2) 0.39 Diabetes mellitus 16 (23.9) 70 (24.1) 121 (26.3) 0.78 Current smoker 40 (59.7) 152 (52.2) 271 (58.8) 0.18 Hypercholesterolemia 33 (49.3) 120 (41.2) 188 (40.8) 0.09 Previous MI 9 (13.4) 40 (13.7) 57 (12.7) 0.85 Previous CABG 0 (0.0) 0 (0.0) 0 (0.0) Killip classification 0.21 I and II 50 (74.6) 220 (75.6) 364 (79.0) III 7 (10.4) 26 (8.9) 51 (11.1) IV 10 (14.9) 45 (15.5) 46 (10.0) Distribution of vessel disease Single-vessel disease 34 (50.7) 97 (33.3) 222 (48.2) Multivessel disease 34 (49.3) 194 (66.7) 239 (51.8) Pre-revascularization TIMI flow (85.1) 249 (85.6) 385 (83.5) 2 10 (14.9) 42 (14.4) 76 (16.5) Mean reperfusion Reperfusion status Successful reperfusion 51 (76.1) 240 (82.5) 404 (87.6) Unsuccessful reperfusion 16 (23.9) 51 (17.5) 57 (12.4) TIMI flow of 2 7 (10.4) 35 (12.0) 42 (9.1) TIMI flow 1 9 (13.4) 16 (5.5) 15 (3.3) Overall 30-d death 10 (14.9) 26 (8.9) 37 (8.3) 0.18 Death after excluded surgery 9/66 (13.6) 26/285 (9.1) 34/453 (7.5) *Data are expressed as mean SD or No. (%) of patients. CABG coronary artery bypass surgery. p 0.008, LCX vs RCA. p 0.018, LCX vs LAD. ECG Manifestations and Coronary Angiographic Features of AMI Caused by LCX Occlusion ECG manifestations of acute LCX occlusion were widely variable, and inferior wall MI was the most frequent presentation (Table 2). More than one third of the patients had dominant LCX, and 22.4% of the patients had a reference lumen diameter (RLD) of the LCX 4.0 mm. The incidence of triple-vessel Table 2 ECG and Angiographic Features of 67 Patients Features Percent Infarction location by ECG Inferior 34.3 Inferior-posterior 34.3 Posterior 6.0 Lateral 7.4 Inferior-lateral 9.0 Non-Q wave 9.0 Angiographic feature of LCX Dominant LCX 34.3 Codominant LCX 29.9 Nondominant LCX 35.8 RLD of LCX 4.0 (mm) 22.4 disease was significantly higher in patients with than in patients without cardiogenic shock (80.0% [8 of 10 patients] vs 17.5% [10 of 57 patients], p ). Furthermore, the combined incidence of dominant LCX and RLD of the LCX 4.0 mm was significantly higher in patients with than in patients without cardiogenic shock (70.0% [7 of 10 patients] vs 3.5% [2 of 57 patients], p ). Angiographic findings demonstrated that these dominant LCXs were always associated with a very small RCA (Fig 1). The incidence of RLD 4.0 mm in patients with dominant LCX was significantly higher than that in patients without dominant LCX (39.1% vs 13.6%, p 0.029). Mean peak CPK level was significantly higher in patients with than in patients without dominant LCX and the RLD of LCX 4.0 mm (7,162 4,641 IU/L vs 3,339 2,294 IU/L, p 0.01). The Determinants of Unsuccessful Reperfusion in Patients With AMI Caused by LCX Occlusion Univariate analysis of the clinical and angiographic features between patients with successful (n 51) and unsuccessful (n 16) reperfusion demonstrated that there was no significant difference between the 2070 Clinical Investigations

4 Figure 1. Case 1. Top left, A: Right anterior oblique view demonstrated a small nondominant RCA. Top center, B: Anteroposterior caudal view demonstrated a plaque rapture with much intracoronary thrombus formation (black arrowheads) in proximal dominant LCX with its diameter 4.0 mm, and total occlusion of distal LCX was observed (black arrows). Top right, C: Angiogram after balloon angioplasty demonstrated successful dilatation of proximal LCX (arrowheads), no-reflow phenomenon of distal LCX (smaller arrows), and distal embolization of obtuse marginal branch (larger arrows). Case 2. Bottom left, D: Right anterior oblique view demonstrated a small nondominant RCA. Bottom center, E: Anteroposterior caudal view demonstrated total occlusion of proximal LCX (arrowhead). Bottom right, F: Angiogram after balloon angioplasty demonstrated successful dilatation of the proximal occlusion (arrowhead), atherosclerosis of distal LCX (larger arrows) and no-reflow phenomenon in the PDA (small arrows). two groups in terms of baseline characteristics (age, sex, current smoking, the presence of hypertension, diabetes mellitus, posterior wall MI), triple-vessel disease, type of reperfusion method, and time to reperfusion. However, patients with unsuccessful reperfusion had a significantly higher incidence of precordial ST-segment depression (81.3% vs 45.1%, p 0.017), complete atrioventricular block (31.3% vs 3.9%, p 0.008), cardiogenic shock (43.8% vs 5.9%, p 0.002), dominant LCX (75.0% vs 21.6%, p 0.001) and RLD of the LCX 4 mm (50.0% vs 13.7%, p 0.004), and poorer left ventricular function ( % vs %, p 0.003) than patients with successful reperfusion. There was no significant difference in successful reperfusion between balloon angioplasty and stenting in either the overall patients (78.7% [37 of 47 patients] vs 70.0% [14 of 20 patients], p 0.45) or in patients with dominant LCX (50.0% [8 of 16 patients] vs 42.9% [3 of 7 patients], p 0.99). By multiple stepwise logistic regression analysis (Table 3), only dominant LCX and cardiogenic shock were independent determinants of unsuccessful reperfusion. Therefore, the significance of precordial ST-segment depression, complete atrioventricular block, and poorer left ventricular function could be attributed to the presence of dominant LCX and cardiogenic shock. Table 3 Multiple Stepwise Logistic Regression Analysis of Significant Variables Associated With Unsuccessful Reperfusion* Variables TIMI-2 flow (n 16) TIMI-3 flow (n 51) Odds Ratio 95% Confidence Interval p Value Dominant LCX (n 23) 12 (75.0) 11 (21.6) Cardiogenic shock (n 10) 7 (43.8) 3 (5.9) *Data are presented as No. (%) unless otherwise indicated. CHEST / 122 / 6/ DECEMBER,

5 Clinical Characteristics and Angiographic Features Related to 30-Day Mortality in Patients With AMI Caused by LCX Occlusion Univariate analysis of the clinical and angiographic features between patients who survived the first 30 days (n 57) and patients who died within the first 30 days (n 10) demonstrated that there was no difference between the two groups in terms of baseline characteristics, precordial ST-segment depression, complete atrioventricular block, and RLD of the LCX 4 mm. However, patients who died within the first 30 days had a significantly higher incidence of triple-vessel disease (77.8% vs 17.5%, p 0.002), unsuccessful reperfusion (66.6% vs 17.5%, p 0.005), dominant LCX (77.8% vs 28.1%, p 0.01), cardiogenic shock (66.7% vs 5.3%, p 0.002), and lower left ventricular ejection fraction ( % vs %, p 0.004) than those who survived the first 30 days after d-pci. By multiple stepwise logistic regression analysis (Table 4), only dominant LCX, cardiogenic shock, and triple-vessel disease were independent determinants of increased 30-day mortality. The overall 30-day mortality of patients with cardiogenic shock was 70% (including one patient with cardiogenic shock who died after surgical intervention). Discussion The Association of Dominant LCX and Cardiogenic Shock With Unsuccessful Reperfusion In the present study, we found that the incidence of LCX with RLD 4.0 mm was 22.4%, and angiographic observations demonstrated that all of these vessels contained high-burden thrombus formation (Fig 1). In this study, we also found that patients with unsuccessful reperfusion had a significantly higher incidence of RLD of the LCX 4.0 mm than patients with successful reperfusion. Recently, we reported that an infarct-related artery with an RLD 4.0 mm was more frequently observed to have high-burden thrombus formation and to have a significantly higher incidence of no-reflow phenomenon after d-pci in patients with cardiogenic shock. 9 It is, thus, not surprising to observe that the LCX with an RLD 4.0 mm was significantly related to a higher incidence of unsuccessful reperfusion in the present study. In the present study, one of our important findings was that a dominant LCX was most significantly related to an increased incidence of unsuccessful reperfusion. However, only 39.1% (9 of 23 patients) of dominant LCXs had a diameter 4.0 mm. Furthermore, it was found that not only dominant LCX and cardiogenic shock but the vessel diameter of LCX 4.0 mm were the independent predictors of unsuccessful reperfusion. These results suggest that other mechanisms rather than an RLD of LCX 4.0 mm play pivotal roles in unsuccessful reperfusion. In practice, we found that the PDA was the vessel that most often developed no-reflow phenomenon after d-pci for acute LCX occlusion (Fig 1). This raises the possibility that the unique anatomic course of the LCX and its final branch, the PDA, might play a peculiar role in unsuccessful reperfusion. Anatomically, a dominant LCX courses along the lateral part of the heart after it arises from the left main coronary artery and gives off its major branches to supply the lateral (obtuse marginal branches), posterior and inferior (PLA and PDA) walls of the left ventricle. The dominant LCX has several acute angles in its course, at its origin (a reverse L curve) and at its distal part to become the PDA (an L curve). These acute angles lead to turbulence and shear stress. Turbulence has been shown to enhance thrombus formation in experimental models, and shear stress has also been shown to induce changes in platelet activity In addition, after acute LCX occlusion, milking action resulting from heart contraction is greatly reduced or even disappears and this leads to stasis and subsequent thrombus formation. These factors might explain why dominant LCX was an independent predictor of unsuccessful reperfusion. Practically, it would be too difficult to prove why cardiogenic shock was an independent predictor of unsuccessful reperfusion in the present study. However, the following two explanations could be taken into consideration. First, cardiogenic shock in our Table 4 Multiple Stepwise Logistic Regression Analysis of Significant Variables Associated With Increased 30-Day Mortality* Variables Mortality (n 9) Survivors (n 57) Odds Ratio 95% Confidence Interval p Value Dominant LCX (n 23) 7 (77.8) 16 (28.1) Cardiogenic shock (n 10) 6 (66.7) 3 (5.3) Triple-vessel disease (n 17) 7 (77.8) 10 (17.5) *Data are presented as No. (%) Clinical Investigations

6 patients was significantly associated with poorer left ventricular function, which leads to increased left ventricular end-diastolic pressure, subsequently retarding achievement of normal LCX blood flow. Second, the elevated left ventricular end-diastolic pressure and hypotensive state during cardiogenic shock provide slow flow and blood stasis, subsequently, no-reflow phenomenon. The Clinical Outcome and the Prognostic Determinants After Acute LCX Occlusion The mortality from acute inferior wall MI with thrombolytic therapy is 10% and it is believed to have a more favorable clinical outcome than anterior wall MI. 4,5,7 However, 70 to 80% of acute inferior wall MIs are caused by RCA occlusion. 1 3 The clinical features and outcome of patients with acute LCX occlusion have not been discussed in detail previously. One of the important findings in the present study was that there was no significant difference of 30-day overall mortality rate between the patients with LCX and LAD infarct-related AMIs. There are two reasonable explanations. First, failure of mechanical reperfusion therapy was associated untoward clinical outcome. 9 In the present study, we found that patients with acute LCX occlusion had significantly higher incidence of unsuccessful reperfusion than patients with acute LAD occlusion. This subsequently led to increased mortality rate in patients with acute LCX occlusion. Second, a previous study 15 demonstrated that left ventricular dysfunction could develop in AMI due to isolated LCX stenosis, and a postmortem study 16 showed that the LCX supplied half as much of the left ventricle as the LAD. Our finding suggested that patients with acute LCX occlusion did not always have a more favorable clinical outcome than patients with acute LAD occlusion. In this study, we demonstrated that cardiogenic shock, dominant LCX, and triple-vessel disease were significantly independent predictors of increased 30-day mortality in patients with LCX infarct-related AMI. Previous studies have found that AMI complicated by cardiogenic shock accounts for 7 to 11% of all MIs. 17,18 The mortality rate of patients with cardiogenic shock could be reduced from 80% using conservative treatment 17 to 40% using d- PCI. 9,17 19 Recently, we reported that the incidence of cardiogenic shock and 30-day mortality rate of patients with cardiogenic shock who underwent d- PCI for AMI were 12.8% and 32.1%, respectively. 9 In this study, the incidence of cardiogenic shock in patients with LCX infarct-related AMI was 14.9%. Surprisingly, we found that the 30-day mortality rate of patients with cardiogenic shock caused by acute LCX occlusion was 60%. We remain uncertain as to why the mortality rate of cardiogenic shock in this subgroup of patients was so high. This increased mortality could be attributed to two factors. First, in this study, the incidence of triple-vessel disease, which has been demonstrated as an independent predictor of increased mortality in patients with cardiogenic shock, 9 was significantly higher in patients with than without cardiogenic shock. Second, patients with cardiogenic shock had a significantly higher incidence of coexistence of dominant LCX and RLD of LCX 4.0 mm. In addition, angiographic findings demonstrated that the dominant LCX was always associated with a very small RCA, and the peak CPK level was significantly higher in patients with than in patients without these distinctive angiographic features. This indicated a larger infarction area associated with poorer left ventricular ejection fraction and cardiogenic shock in patients with these distinctive angiographic features, and consequently a higher 30-day mortality. Our study had several limitations. First, the number of patients in this study was small; therefore, our results should be viewed as preliminary and await confirmation by larger clinical trials. Second, our study was not specifically designed to evaluate longterm clinical outcomes; therefore, it could not provide long-term clinical outcome in this clinical setting. Third, platelet glycoprotein IIb/IIIa blockade, which has been shown to substantially improve clinical outcomes in elective or primary percutaneous coronary intervention, 20 was not used in this study. Whether adjunctive therapy with platelet glycoprotein IIb/IIIa blockade could improve the perfusion rate and clinical outcome of patients with LCX infarct-related AMI remains to be determined. Finally, the role of Thrombectomy with Angiojet Catheter 21 or PercuSurge Guard Wire Distal Balloon Protection System 22 to remove high-burden thrombus and to improve the clinical outcome of the patients with AMI in this clinical setting had not been evaluated in this study. In conclusion, LCX infarct-related AMI has its unique clinical features and does not always indicate a more favorable clinical outcome, especially in patients with cardiogenic shock. Our results demonstrated that the presence of dominant LCX and cardiogenic shock were independent determinants of unsuccessful reperfusion and the presence of dominant LCX, cardiogenic shock, and triple-vessel disease were independent determinants of increased 30-day mortality in this clinical setting. CHEST / 122 / 6/ DECEMBER,

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