Recognition of Left Main Occlusion in Acute Coronary Syndrome

Original Article Acta Cardiol Sin 2004;20:139 46 Coronary Artery Disease Recognition of Left Main Occlusion in Acute Coronary Syndrome Yi Chen, Yeun Tarl Fresner Ng Jao, Ching-Chang Fang, Ching-Lung Yu, Chiliang Chen and Shih-Pu Wang Background: Left main coronary artery (LMCA) occlusion may result in acute coronary syndrome (ACS) or sudden death. ST elevation in lead avr is reported to be valuable in recognizing LM occlusion. Early recognition of electrocardiogram (ECG) changes, such as ST elevation in avr, is helpful in averting this disaster. Methods: From January 1999 to August 2003, 22 patients with ACS associated with left main (LM) disease who underwent emergent percutaneous coronary intervention (PCI), were included. Patients were grouped according to the infarct-related artery (IRA). Group I consisted of 9 patients having the LM or LM distal portion with extension to the left anterior descending (LAD) artery orifice as its IRA, while group II included 13 patients who had significant LM stenosis but with a different IRA. Results: ST elevation in avr was noted in all patients in group I and only 7 patients in group II. Its amplitude was significantly higher in group I (p = 0.003). An elevation of > 0.1 mv was strongly predictive of LM occlusion (p = 0.004). Right bundle branch block (RBBB) was only seen in group I (p = 0.003). Creatine kinase-mb (CK-MB) was also higher in group I (p = 0.013). Conclusion: Patients with ACS having the LM as culprit lesion are characterized by RBBB and ST elevation in avr. ST elevation and its amplitude in avr are strongly related with LM disease. These patients should undergo emergent coronary arteriogram and intervention. Key Words: Left main occlusion Acute coronary syndrome Electrocardiogram INTRODUCTION Left main coronary artery (LMCA) occlusion is a serious clinical condition. Despite its low incidence, the prognosis is grave. It may present as sudden death, complete heart block, shock and/or acute coronary syndrome (ACS). Surgery is usually too late to initiate, so that percutaneous coronary intervention (PCI) is utilized to obtain immediate vessel patency. However, this modality is associated with a high mortality and restenosis rate. 1,2 Early recognition and emergent PCI may be lifesaving. The best and easiest available noninvasive modality in the emergency room (ER) is an electrocardiogram (ECG). However, ECG may be normal or may present with findings compatible with ACS, but be unable to distinguish an LMCA from other coronary artery occlusion. For the past few years, reports have shown that the ST segment deviation in lead avr is an important predictor of acute LM occlusion, and is valuable in its prognosis. Also, an ST elevation of more than 0.05 mv in lead avr is indicative of LM occlusion in up to 88% of patients with acute myocardial infarction (AMI). 3,4 We therefore undertook this study to determine if we could obtain similar findings. Received: June 17, 2003 Accepted: March 24, 2004 Cardiovascular Center, Tainan Municipal Hospital, Tainan, Taiwan. Address correspondence and reprint requests to: Dr. Shih-Pu Wang, Cardiovascular Center, Tainan Municipal Hospital, No. 670, Chung-Te Road, Tainan, 701, Taiwan. Tel: 886-6-260-5692; Fax: 886-6-260-6351; E-mail: wangsb@mail.tmh.org.tw METHODS Patients From January 1999 to August 2003, patients who 139 Acta Cardiol Sin 2004;20:139 46

Yi Chen et al. underwent emergent PCI in our hospital due to ACS associated with LM disease were selected. The diagnosis of ACS was based on elevations of serum creatine kinase MB form (CK-MB) twice the upper normal limit (25 IU/L) measured every 6 hours, the presence of anginal symptom and ST segment elevations in more than 2 leads on ECG. Only patients with complete medical histories, available ECG, coronary angiograms, and CK-MB levels were included in the study. Of the 24 cases reviewed, only 22 patients were included. Two patients had incomplete data and were excluded. There were 18 men and 4 women with a mean age of 65 years (range 47 to 77 years). Patients were grouped according to the infarct-related artery (IRA). They were placed in group I when the IRA was the LM or LM distal portion with extension to the LAD orifice, and in group II when the IRA was not the aforementioned arteries but was with a significant (> 50%) stenosis of the LM. Group I had 9 patients, while group II consisted of 13 patients. Electrocardiography Serial 12-lead ECGs were obtained in the ER, a few minutes to hours on admission prior to and after PCI. The 1 taken immediately upon arrival at the ER was used as basis for analysis. ST segment elevation was defined as a rise of more than 0.05 mv in the limb leads and 0.1 mv in the precordial leads. Its magnitude and location were also recorded. Particular attention was focused in leads avr and V1. Then, ST segment measurements were subjected to statistical analysis. Cardiac catheterization Cardiac catheterization was performed immediately on all patients upon diagnosis of AMI at the ER. A stenosis of more than 50% in diameter of 1 or more major epicardial artery was considered significant. The IRA or the culprit lesion was defined as a) total occlusion; b) the most severe lesion; and 3) thrombus formation in the coronary artery. The type of reperfusion therapy was chosen at the operator s discretion. Statistical analysis Continuous variables are presented as mean SD and were compared using the unpaired Student t-test. Categoric or discrete variables are presented as frequencies and percentages. They were compared using Fisher s exact or 2 test when appropriate. ST elevations in avr, V1 and CK-MB levels are presented as qualitative (with or without) or as quantitative (actual measurements of elevations) variables. Variables such as ST segment elevation in leads avr and V1, creatine phosphokinase (CPK), and CK-MB levels were subjected to univariate analysis or Spearman s rho correlation. A stepwise multivariate logistic regression analysis was later used to determine the predictors of LM artery stenosis, and presented as the p value. A p value of less than 0.05 was considered significant. Due to the small population of the study, the sensitivity and specificity rates, as well as the positive and negative predictive values (PPV, NPV) of variables which were strong predictors using univariate analysis were calculated, and are presented as percentages. RESULTS There were no significant differences in patients clinical characteristics between the 2 groups, except for a lower systolic blood pressure (taken in the ER), and more Killip IV patients in group I. The rest of the baseline clinical characteristics are shown in Table 1. The Table 1. Baseline clinical characteristics Group I (n = 9)Group II (n = 13) p value Age 65.2 5.4 64.5 10.6 0.846 Male (%) 9 (100) 9 (69) 0.198 Smoking (%) 7 (78) 7 (54) 0.484 Hypertension (%) 5 (55) 3 (23) 0.258 Diabetes Mellitus (%) 3 (33) 2 (15) 0.634 Dyslipidemia (%) 0 5 (38) 0.114 Heart rate 90.0 29.1 78.3 21.0 0.285 SBP 99.3 40.1 132.2 26.0 0.030 Killip classification I(%) 1(11) 5(38) 0.360 II (%) 2 (22) 5 (38) 0.743 III (%) 1 (11) 3 (23) 0.876 IV (%) 5 (55) 0 0.011 Death(%) 4(44) 2(15) 0.308 Treatments Medications (%) 2 (22) 5 (38) PCI (%) 6 (67) 4 (31) CABG (%) 1 (11) 4 (31) SBP = systolic blood pressure, PCI = percutaneous coronary intervention, CABG = coronary artery bypass graft surgery. Acta Cardiol Sin 2004;20:139 46 140

Recognition of Left Main Occlusion in Acute Coronary Syndrome culprit lesion or IRA in group I was the LM in 7 patients and LM distal portion with extension to the LAD-orifice in 2 patients. The majority of the IRA in group II was the right coronary artery (RCA). The rest of the angiographic data are presented in Table 2. Lead avr showed ST segment elevation in 100% (9/9) of patients in group I and in 54% (7/13) of patients in group II, with a sensitivity rate and a negative predictive value (NPV) of 100%. Also, the magnitude of the ST segment elevation in lead avr was significantly higher in group I (p = 0.003). In 1 patient belonging to group I, ECG on admission showed ST elevation in leads avr and V1 (Figure 1A). AMI due to a LM occlusion was proven by cardiac catheterization when it showed a normal RCA and LM occlusion with minimal flow to the proximal LAD (Figure 2A). Follow-up ECG after PCI showed regressive ST segment changes on IRA related leads (Figure 1B). Coronary arteriogram after LM stenting showed thrombolysis in myocardial infarction (TIMI) 3 antegrade flow to both LAD and LCX Table 2. Angiographic characteristics Group1(n=9)Group2(n=13) IRA LM/LM and LAD orifice (%) LAD-M/LAD-D (%) RCA (%) LCX (%) Single-vessel disease (%) Multi-vessel disease (%) 7/2 (78/22) 0 0 0 5(55) 4(44) 0 2/1 (15/8) 9(69) 1(8) 3(23) 10 (77) IRA = infarct related artery; LM = left main; LAD-P = left anterior descending artery-proximal segment; LAD-M = left anterior descending artery-middle segment; LAD-D = left anterior descending-distal segment; RCA = right coronary artery; LCX = left circumflex artery. April 16, 2003 April 17, 2003 A Prior to PCI B Post PCI Figure 1. ECG in AMI from LM occlusion. (A) Prior to PCI: ST segment elevation in avr and V1, with higher magnitude in V1. (B) Two hours after LM stenting: regression of ST changes in IRA-related leads. 141 Acta Cardiol Sin 2004;20:139 46

Yi Chen et al. A B Figure 2. Coronary arteriogram of the same patient. (A) Total occlusion of LM with minimal flow through the proximal segment of the LAD. (B) Final result after LM stenting showing TIMI-3 antegrade flow to both LAD and LCX. Table 3. Electrocardiographic data and cardiac enzyme levels Group I (n = 9) Group II (n = 13) p value Sinus rhythm (%) 8 (89) 11 (85) 0.714 RBBB (%) 6 (67) 0 0.003 LVH (%) 0 2 (15) 0.650 STelevationinaVR(%)* 9(100) 7(54) 0.087 Magnitude of ST elevation in avr (mv) # 0.19 0.13 0.05 0.06 0.003 Magnitude of ST elevation in V1 (mv) # -0.04 0.18 0.06 0.10 0.110 CPK (IU/L) 5724.6 4696.5 2371.6 3421.2 0.066 CK-MB (IU/L) 531.0 558.5 101.5 110.3 0.013 RBBB = right bundle branch block; LVH = left ventricular hypertrophy; CPK = creatine phosphokinase; CK-MB = creatine kinase- MB isoenzyme. * qualitative; # quantitative. (Figure 2B). The occurrence of RBBB was seen solely in group I (67%). There were more deaths during admission, higher CPK and CK-MB levels in this group. CK-MB was also significantly elevated (p = 0.013). Also, a majority of patients in group I underwent PCI, with only 1 patient undergoing coronary artery bypass graft surgery (CABG). More patients underwent CABG in group II, which may be attributed to the greater number of patients with multi-vessel disease. The rest of the data is tabulated in Table 3. Independent variables tested using univariate and multivariate analysis showed only both CK-MB levels and ST elevation in lead avr as significant predictors of LM disease (Table 4). The sensitivity and specificity rates, as well as the positive predictive value (PPV) and NPV of individual variables on how they affected LM diagnosis, are shown in Table 5. Table 4. Univariate and multivariate analysis with left main coronary artery as the dependent variable Variable p value univariate multivariate ST elevation in avr # 0.002 0.004 T elevation in V1 # 0.238 ---- CPK 0.092 ---- CK-MB 0.031 0.017 CPK = creatine phosphokinase; CK-MB = creatine kinase-mb isoenzyme. # quantitative. DISCUSSION This study shows that the higher the ST elevation in lead avr, the more useful it is for predicting LMCA as culprit lesion in patients with ACS. Patients with significant LM disease, even if LM was not the culprit lesion of Acta Cardiol Sin 2004;20:139 46 142

Recognition of Left Main Occlusion in Acute Coronary Syndrome Table 5. Sensitivity, specificity rates, and positive and negative predictive values of independent variables in diagnosing left main lesion Variables Sensitivity rate (%) Specificity rate (%) PPV (%) NPV (%) ST elevation in avr * 100 46 56 100 ST elevation in avr > 0.1 mv # 67 92 86 80 ST elevation in V1 33 54 33 54 CK-MB elevation * 100 23 47 100 CK-MB elevation > 400 U/L # 56 100 100 77 Presence of RBBB alone 67 100 100 81 ST elevation + RBBB 67 100 100 70 PPV = positive predictive value; NPV = negative predictive value; CK-MB = creatine kinase-mb isoenzyme; RBBB = right bundle branch block. * qualitative; # quantitative. ACS, also exhibited ST elevation in lead avr. However, in these cases, the ST elevation was lower in magnitude. There is no cutoff level as to the magnitude of ST elevationinleadavrinpredictinglmcalesions.inthis study, a cut-off value of > 0.1 mv revealed almost threefold predictability for an LMCA lesion in ACS, with a specificity rate of 92% and a PPV of 86%. This is important since 7 patients in group II also had ST elevations in lead avr. Of these, aside from the accompanying LM lesion, 6 cases had the RCA as the IRA. So, the magnitude of the ST elevation (> 0.1 mv) is of great importance, not only to predict the presence or absence of LM disease, but also to show if it s the culprit lesion. This observation is supported by the 2 patients with middle segment and 1 with distal segment LAD culprit lesions in this study who did not have the aforementioned changes. The avr on a 12-lead ECG provides valuable information on the right upper side of the heart. However, it is not usually used in clinical practice, and is commonly seen and interpreted as reciprocal information from the left lateral leads, or for observing endocardial electrographic changes. During the 1980 s, ST elevation in lead avr was reported to be associated with LM occlusion. 5 But even up till the late 1990 s, ECG interpreters often ignored the avr. 6 For the past few years, reports have proven that ST elevation in lead avr was not only related to a LM occlusion, but also indicated an anterior wall infarction. As was mentioned earlier, and as proven in our data, ST elevation in lead avr strongly suggests a significant LM lesion. However, if accompanied by ST elevation in lead V1, the specificity of an LM lesion acting as the culprit vessel increases. Assuming that both leads avr and V1 have ST elevations, a higher magnitude of ST elevation in lead avr compared to lead V1 is very specific for LM occlusion. 3,5,7-10 According to Yamaji et al, 3 the incidence of ST elevation in lead avr of lower magnitude or less than that of V1 in AMI from LM occlusion is less than 20%, as in this series. An important observation in Table 3 is that the ST elevation of V1 in group I had a negative value. This is due to the fact that 6 out of 9 patients in this group had RBBB. The ST segment of RBBB is pointing downwards, hence the negative deflection on ECG. All RBBB in this series was recorded during the first ECG taken in the ER. Whether or not the RBBB persisted or resolved in the succeeding ECGs after PCI was not within the scope of this study, but there is a follow-up study currently in progress at our hospital. RBBB usually reflects local ischemia at the base of the heart, 3,9 and may indicate a large infarct area and may also be seen in fatal diseases of the left heart. The cardiac septum is supplied by the septal branch originating from the LAD, and is the physiologic explanation for RBBB occurrence in LM culprit lesions. And since an ST elevation in lead avr points to a significant LM lesion, but does not necessarily equate to a culprit vessel, we strongly believe that an accompanying RBBB or ST elevation in lead V1 of lower magnitude than avr increases the specificity (100%) and PPV (100%) for pointing out the LMCA as the culprit vessel in ACS. This is clearly shown in our data. Patients who present with total LM occlusion associated with RBBB, ST elevation in lead avr, shock and cardiac arrest are known as left main shock syndrome. 11 Patients with this condition have a high mortality rate, as in this series. Therefore, a high index of suspicion, with accompanying symptoms and aforementioned new ECG 143 Acta Cardiol Sin 2004;20:139 46

Yi Chen et al. findings, are helpful to arrive at a diagnosis early. In the literature, RBBB was only noted in 2 patients with AMI from an LM occlusion. However, in this series, there were 6 (67%) patients with RBBB in group I alone and none in group II. Exercise-induced ST depression in lead V5 and concomitant ST elevation in lead avr may indicate ischemia of the anterior myocardium or significant stenosis of the LAD. V1 may also be involved to the same degree as avr. 5,7,12 In patients without previous myocardial infarction, the severity of coronary artery disease and ventricular dysfunction in exercise-induced ST elevation did not differ from patients with ST depression. However, if prior myocardial infarction was present, the exercise-induced ST elevation appeared to be a marker of depressed left ventricular function, 13 which consists of left ventricular function abnormalities and an ejection fraction (EF) of less than 50%. This abnormality is also seen in non-q myocardial infarction, triple-vessel disease and LM involvement. 14 LM disease is usually not an isolated coronary artery event, but is associated with individual LAD, LCX, RCA or even triple-vessel disease. Co-occurrence with 1 or more coronary arteries may alter ECG manifestations, as the magnitude of ST elevation in lead avr may change in relation to V1. Diffuse ST depression over the inferior and anteriolateral leads with ST elevation in leads avr, avl, V1 and V2 are typical ECG manifestations of AMI secondary to an LM occlusion. 15 ECG is only 1 of the many diagnostic modalities used in detecting myocardial infarction from an LM occlusion. Therefore, recognizing the significance of ST elevation in lead avr and subjecting the patient to emergent cardiac catheterization are lifesaving. Lastly, the significance of CK-MB being a strong predictor of LM occlusion in AMI (p = 0.017) deserves further study. In our series, a cut-off value of 400 U/L was strongly associated with LM occlusion (specificity rate 100%; PPV 100%), but not with other coronary arteries; this may reflect a large infarct area resulting from a LM occlusion. However, several factors may have influenced the CK-MB levels and may not truly represent a LM lesion. Since 5 out of 9 patients (55%) in group I and none in group II were in shock (Killip IV) upon presentation, CK-MB and CPK levels may not truly reflect myocardial damage solely. The same reason can be offered regarding ECG changes upon ER presentation. A small sample size may also affect this outcome. Though CPK levels were also higher in group I, these values did not reach statistical significance. Further correlation between CK-MB, CPK and LM occlusion in ACS, with or without the presence of shock, is prudent. LIMITATIONS Several limitations need to be emphasized. This was a retrospective and descriptive study in a single hospital over a period of 4 years. Also, the sample size was small, so caution must be exercised in interpreting our data. Secondly, since there was great variation of the time from the start of symptoms until arrival at the ER, uniformity of the timetable for taking the ECG was not possible. This factor can not be standardized, since the time at which the patient decided to consult our ER could not be controlled. This may have also affected our results, since changes in ECG patterns are associated with the duration of ischemia and symptoms. CK-MB levels and ECG changes may have also been affected by a patient in shock due to impaired coronary perfusion at the time of presentation. However, despite these limitations, we cannot ignore these results, since they are in concert and comparable with other reports in the literature. CONCLUSION ST elevation in lead avr is strongly associated with LM occlusion. Any degree of ST elevation in lead avr greater than 0.05 mv should raise suspicion of a major proximal coronary occlusion, which includes the LMCA. A value greater than 0.1 mv, however, increases diagnostic accuracy. Whether the magnitude of ST elevation in lead avr is greater or lower than V1 strongly indicates a high septal ischemia or injury from myocardial infarction. The presence of RBBB with ST elevation in lead avr increases the possibility that the LM is the culprit vessel in ACS. A CK-MB value of > 400 IU/L may also be associated with ACS secondary to a LM occlusion. Patients with ST elevation in lead avr and ACS Acta Cardiol Sin 2004;20:139 46 144

Recognition of Left Main Occlusion in Acute Coronary Syndrome should undergo emergent coronary arteriogram and intervention. REFERENCES 1. Lee KW, Fang CC, Jao TC, et al. Stenting in the unprotected left main artery: immediate result and late outcome. Acta Cardiol Sin 2000;16:231-8. 2. Spiecker M, Erbel R, Rupprecht HT, Meyer J. Emergency angioplasty of totally occluded left main coronary artery in acute myocardial infarction and unstable angina pectoris: institutional experience and literature review. Eur Heart J 1994;15:602-7. 3. Yamaji H, Iwasaki K, Kusachi S, et al. Prediction of acute left main coronary artery obstruction by 12-lead electrocardiography: ST segment elevation in lead avr with less ST segment elevation in lead V1. J Am Coll Cardiol 2001;38:1348-54. 4. Hori T, Kurosawa T, Yoshida M, et al. Factors predicting mortality in patients after myocardial infarction caused by left main coronary artery occlusion: significance of ST segment elevation in both avr and avl leads. Jpn Heart J 2000;41: 571-81. 5. Atie J, Brugada P, Brugada j, et al. Clinical presentation and prognosis of left main coronary artery disease in the 1980s. Eur Heart J 1991;12:495-502. 6. Pahlm US, Pahlm O, Wagner GS. The standard 11-lead ECG: neglect of lead avr in the classical limb lead display. J Electrocardiol 1996;29(suppl):270-4. 7. Nakamori H, Iwasaka T, Shimada T, et al. Clinical significance of S-T segment elevation in lead avr in anterior myocardial infarction: assessment by thallium-201 exercise scintigraphy. Cardiology 1995;86:147-51. 8. Gorgels AP, Vos MA, Mulleneers R, et al. Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior wall infarction. JAm Coll Cardiol 1999;34:389-95. 9. Gorgels AP, Engelen DJM, Wellens JJ. Lead avr, a mostly ignored but very valuable lead in clinical eletrocardiography [Editorial comment]. J Am Coll Cardiol 2001;38:1355-6. 10. Banning AP. Primary angioplasty and stenting of left main coronary occlusion. Heart 1998;79:528-9. 11. Quigley RL, Milano CA, Smith LR, et al. Prognosis and management of anterolateral myocardial infarction in patients with severe left main disease and cardiogenic shock: the left main shock syndrome. Circulation 1993;88:II65-70. 12. Michaelides AP, Psomadaki ZD, Richter DJ, et al. Significance of exercise-induced simultaneous ST segment changes in leads avr and V5. Int J Cardiol 1999;71:49-56. 13. Stiles GL, Rosati RA, Wallace AG. Clinical relevance of exerciseinduced ST segment elevation. Am J Cardiol 1980;46: 931-6. 14. Gash AK, Warner HF, Zadrozny JH, et al. Electrocardiographic ST-T patterns, extent of coronary artery disease, and left ventricular performance following non-q-wave myocardial infarction. Cathet CV Diagn 1985;11:223-33. 15. Sclarovsky S, Kjell N, Birnbaum Y. Manifestation of the left main coronary artery stenosis is diffuse ST depression in inferior and precordial leads on ECG. J Am Coll Cardiol 2002;40:575-6. 145 Acta Cardiol Sin 2004;20:139 46

Original Article Acta Cardiol Sin 2004;20:139 46 左主幹阻塞引發急性冠心症之辨認 陳怡吳原大方慶章于慶龍陳佶良王石補台南市立醫院心臟血管中心 背景冠狀動脈左主幹阻塞可引發急性冠心症或死亡, 發生率雖低但後果嚴重, 最新報告心電圖上 avr 之 ST 波昇高有助於左主幹阻塞之早期診斷, 注意心電圖之改變, 有助於評估及治療此一疾病 方法從 1999 年到 2003 年, 本院有 22 位急性冠心症合併左主幹阻塞患者, 這些患者均有冠狀動脈攝影證明及介入性治療 這些患者視左主幹冠狀動脈是否為梗塞相關動脈分成兩組, 第一組有 9 位患者, 其梗塞相關動脈為左主幹冠狀動脈或左前降枝的開口, 第二組有 13 位患者, 其梗塞相關動脈不是左主幹冠狀動脈或左前降枝的開口, 但左主幹冠狀動脈有顯著狹窄 臨床病史 心電圖 心肌酵素及冠狀動脈攝影的變化為分析的要點 結果心電圖上 avr 之 ST 波段在第一組患者全部都上昇, 第二組患者僅有 7 位有此現象 在輻度上, 第一組患者有顯著的上昇 輻度大於 0.1 mv 必須考慮是左主幹冠狀動脈阻塞的急性冠心症 第一組患者有較高的死亡率及 CK-MB 右束傳導障礙也在第一組患者中較常見到 結論急性冠心症合併左主幹阻塞患者, 其心電圖之重要表徵為右束傳導障礙及 avr 之 ST 波段昇高 avr 之 ST 波段昇高, 應疑為左主幹有顯著阻塞 急性冠心症合併 avr 之 ST 波段昇高的患者, 應行緊急冠狀動脈攝影及介入性治療 關鍵詞 : 左主幹阻塞 急性冠心症 心電圖 146