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Acute Myocardial Infarction Due to Left Circumflex Artery Occlusion and Significance of ST-Segment Elevation
Acute Myocardial Infarction Due to Left Circumflex Artery Occlusion and Significance of ST-Segment Elevation Aaron M. From, MDa, Patricia J.M. Best, MDa, Ryan J. Lennon, MSb, Charanjit S. Rihal, MDa, and Abhiram Prasad, MDa,* Acute occlusion of the left circumflex (LC) artery can be difficult to diagnose. The aim of the present study was to assess the incidence of LC occlusion in patients with acute myocardial infarction (AMI) requiring percutaneous coronary intervention (PCI), the frequency of ST-segment versus non–ST-segment elevation presentation among them, and to correlate the electrocardiographic findings with the outcomes. The clinical characteristics and outcomes of consecutive patients from November 2001 through December 2007 with AMI within 7 days before PCI of a single acutely occluded culprit vessel were included in the present analysis. Of the 1,500 patients, the culprit lesion was located in the right coronary artery, left anterior descending artery, or LC artery in 44.7%, 35.8%, and 19.5% of patients, respectively. Of the 1,500 patients, 72% presented with ST-segment elevation AMI, but only 43% were patients with a LC lesion (n ⴝ 127). PCI was significantly less likely (80%, 83%, and 70% for right coronary, left anterior descending, and LC artery, respectively; p <0.001) to be performed within 24 hours for LC occlusions than for occlusions in the other territories. Among those with a non–ST-segment elevation AMI, the highest post-PCI troponin levels were in patients with a LC artery occlusion (median 1.4, 1.3, and 2.5 ng/ml; p <0.001). No significant difference was found in the in-hospital mortality (4.4%, 7.4%, and 6.5%; p ⴝ 0.66) or major adverse cardiovascular event (9.2%, 13.9%, and 11.6%; p ⴝ 0.53) rates for right, left anterior descending, and LC occlusions, respectively. In conclusion, our results have demonstrated that in clinical practice, the LC artery is the least frequent culprit vessel among patients treated invasively for AMI. Patients with LC occlusion are less likely to present with ST-segment elevation AMI and have emergency PCI. The study results suggest that detection of these patients has been suboptimal, highlighting the need to improve the diagnostic approach toward the detection of an acutely occluded LC artery. © 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:1081–1085) Acute flow-limiting coronary occlusion is associated with the greatest risk of adverse outcomes among patients with myocardial infarction.1,2 The presence of ST-segment elevation on the electrocardiogram (ECG) is the criterion used in clinical practice to identify patients with acutely occluded coronary arteries, and current treatment pathways triage accordingly. A major limitation of this approach is that the 12-lead ECG does not detect STsegment elevation in all patients with acutely occluded culprit arteries and, especially, lacks sensitivity in the left circumflex (LC) territory.3– 6 Failure to detect an occluded LC artery is not without consequences, because it supplies a significant area of the left ventricle.7 Current guidelines have recommended placement of 3 additional leads on the posterior wall of the chest to increase the sensitivity of the ECG.8,9 Despite this, data from randomized clinical trials of ST-segment elevation acute myocardial infarction (STEMI) have repeatedly shown that a Division of Cardiovascular Diseases, Department of Internal Medicine and bDivision of Biostatistics, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, Minnesota. Manuscript received April 15, 2010; manuscript received and accepted June 5, 2010. *Corresponding author: Tel: (507) 538-6325; fax: (507) 255-2550. E-mail address: [email protected] (A. Prasad).
0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.06.016
LC is the least frequent culprit artery among the patients enrolled.10,11 There is a paucity of data on whether the same holds true in routine clinical practice. We hypothesized that, despite the increased awareness of the difficulty of diagnosing an occluded LC artery, patients with infarcts in this territory remain less likely to undergo revascularization. Thus, the aim of the present study was to assess the incidence of LC occlusion in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), the frequency of STsegment versus non–ST segment elevation presentation among them, and to correlate the electrocardiographic findings with outcomes. Methods The study was conducted among consecutive patients who had undergone PCI from November 2001 through December 2007 with the following inclusion criteria: AMI within 7 days preceding PCI, and a single culprit vessel with either 100% occlusion or ⱖ90% stenosis with less than Thrombolysis In Myocardial Infarction 3 flow. Patients with graft conduit interventions or left main interventions or those who had undergone elective procedures were excluded. www.ajconline.org
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Table 1 Clinical, angiographic, and procedural characteristics stratified by culprit artery Variable Age (years) Men Diabetes mellitus Hypertension* Hypercholesterolemia† Body mass index (kg/m2) Chest pain before procedure Preprocedural shock Peripheral vascular disease Cerebrovascular disease Thrombolytic agents before percutaneous coronary intervention Timing of percutaneous coronary intervention ⱕ24 Hours from acute myocardial infarction ⬎24 Hours from acute myocardial infarction Single-vessel disease Angiographic presence of thrombus Preprocedural Thrombolysis In Myocardial Infarction 0 flow Stents per patient Drug-eluting stent use Thrombectomy device use Glycoprotein IIb/IIIa inhibitor use Procedural success Peak preprocedure troponin T‡ ST-segment elevation presentation Non–ST-segment elevation presentation Peak postprocedure troponin T‡ ST-segment elevation presentation Non–ST-segment elevation presentation
Right (n ⫽ 670)
LAD (n ⫽ 537)
LC (n ⫽ 293)
p Value
64.5 ⫾ 13.3 475 (71%) 107 (16%) 414 (67%) 404 (71%) 28.9 ⫾ 5.5 634 (95%) 97 (15%) 46 (7%) 59 (9%) 103 (16%)
64.4 ⫾ 13.6 370 (69%) 100 (19%) 317 (65%) 322 (70%) 29.2 ⫾ 5.8 505 (94%) 76 (14%) 29 (6%) 48 (9%) 64 (12%)
64.0 ⫾ 13.3 225 (77%) 53 (18%) 186 (69%) 182 (74%) 29.5 ⫾ 5.6 279 (95%) 39 (13%) 27 (9%) 26 (9%) 21 (7%)
0.85 0.05 0.46 0.55 0.56 0.32 0.77 0.87 0.13 0.99 0.001 ⬍0.001
539 (80%) 131 (20%) 315 (48%) 568 (90%) 425 (70%) 1.3 ⫾ 0.9 296 (44%) 72 (11%) 540 (81%) 604 (90%) 0.2 (0.0, 0.8) 0.1 (0.0, 0.6) 0.5 (0.2, 1.0) 3.2 (1.4, 6.1) 4.0 (1.9, 7.0) 1.4 (0.6, 2.7)
445 (83%) 92 (17%) 309 (59%) 426 (85%) 329 (66%) 1.2 ⫾ 0.7 214 (40%) 27 (5%) 437 (81%) 474 (88%) 0.3 (0.0, 1.3) 0.2 (0.0, 1.2) 0.5 (0.2, 1.4) 4.2 (1.5, 9.7) 5.7 (2.6, 11.5) 1.3 (0.6, 2.8)
206 (70%) 87 (30%) 137 (48%) 215 (80%) 182 (71%) 1.0 ⫾ 0.7 130 (44%) 15 (5%) 245 (84%) 250 (85%) 0.5 (0.1, 1.7) 0.2 (0.0, 1.7) 0.6 (0.2, 1.5) 3.1 (1.5, 5.9) 4.9 (2.5, 9.4) 2.5 (1.1, 4.2)
⬍0.001 ⬍0.001 0.33 ⬍0.001 0.26 ⬍0.001 0.54 0.09 ⬍0.001 ⬍0.001 0.053 ⬍0.001 ⬍0.001 ⬍0.001
* Documented history of hypertension treated with medication. † History of total cholesterol level ⬎240 mg/dl. ‡ Median (quartile 1, quartile 3). LAD ⫽ left anterior descending; LC ⫽ left circumflex.
A total of 1,566 patients with AMI who had undergone PCI for a single culprit vessel were identified. The institutional review board approved the present study. The diagnosis of AMI before PCI was determined from the final discharge diagnosis in the clinical records. To determine the accuracy of the diagnosis of STEMI versus non–STEMI (NSTEMI), one investigator (PJMB) retrospectively reviewed the preprocedural ECG to confirm the presence or absence of ST-segment elevation. STEMI was diagnosed if ⱖ1 mm of ST-segment elevation was present in 2 contiguous leads. All other patients with AMI were classified as having NSTEMI. When the ECG before revascularization was not available in the medical records (patients transferred from other hospitals), the description in the medical records from the attending cardiologist who had reviewed the ECG was used to determine the diagnosis. Blood samples for cardiac troponin T levels were collected at admission (before PCI) and 8 and 16 hours after PCI. The peak postprocedure values were used in the present analysis. A sensitive and precise third-generation assay (Elecsys, Roche Diagnostics, Indianapolis, Indiana) was used with an upper limit of normal of ⬍0.01 ng/ml (ninety-ninth percentile). The number of diseased coronary arteries was defined by the number of major arteries with ⱖ70% stenosis on visual assessment. Major adverse cardiovascular events were de-
fined as one or more of the following: in-hospital death, Q-wave myocardial infarction, the need for urgent or emergent coronary artery bypass grafting during the index hospitalization, or cerebrovascular accident, defined as transient ischemic attack or stroke. In-hospital deaths included all deaths during the index hospital admission. Procedural success was defined as a reduction of residual luminal diameter stenosis to ⬍20% without in-hospital death, Qwave myocardial infarction, or the need for emergency coronary artery bypass grafting. Long-term outcomes included all-cause mortality. Continuous variables were summarized as the mean ⫾ SD if distributed symmetrically or with mild skew and compared using one-way analysis of variance. Other continuous variables that were skewed were summarized as the median (interquartile range) and compared using the Kruskal-Wallis rank sum test. Discrete variables are presented as frequency (percentages) and were compared using Pearson’s chi-square test. Missing values were excluded from the denominator in the calculation of the percentages. Kaplan-Meier methods were used to estimate the survival rates on follow-up with comparisons tested using the log-rank test. All hypothesis tests were 2-sided with a 0.05 type I error rate. Analyses were performed using Statistical Analysis Systems, version 9.1 (SAS Institute, Cary, North Carolina).
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Figure 3. Post-PCI troponin T levels (interquartile range and median) according to culprit vessel and infarct type.
Figure 1. Relative frequency of STEMI versus NSTEMI presentation according to culprit artery.
Figure 4. Two-year mortality rates according to culprit vessel and infarct type.
Figure 2. Proportion of patients undergoing PCI within 24 hours of presentation according to culprit vessel and infarct type.
Results The baseline characteristics of the 1,500 patients with AMI are listed in Table 1, according to the culprit artery. The culprit lesion was located in the right, left anterior descending (LAD), or LC artery in 44.7%, 35.8%, and 19.5% of patients, respectively. Patients with acutely occluded LC arteries were more likely to have undergone PCI ⬎24 hours after the onset of the AMI than those with a culprit lesion in the LAD or right arteries (Table 1). In the entire cohort, the preprocedural troponin values were greater in patients with a LC occlusion. No significant difference was found in the in-hospital mortality (4.4%, 7.4%, and 6.5%, respectively; p ⫽ 0.66) or major adverse cardiovascular event (9.2%, 13.9%, and 11.6%, respectively; p ⫽ 0.53) rates for patients with right, LAD, and LC occlusions. A total of 1,077 patients (72%) presented with STEMI and 423 (28%) presented with NSTEMI. Figure 1 demonstrates the relative frequency of STEMI versus NSTEMI
presentation according to the culprit artery. Only 127 patients (12%) with STEMI had a culprit lesion in the LC artery compared to 166 patients (39%) presenting with NSTEMI. Figure 2 illustrates the proportion of patients undergoing PCI within 24 hours of presentation according to the culprit vessel and infarct type. PCI was performed within 24 hours in 957 (89%) of 1,077 patients presenting with STEMI and 233 (55%) of the 423 patients presenting with NSTEMI. The pre- and postprocedural troponin T levels according to the culprit vessel and infarct type are summarized in Figure 3 and Table 1. Of the NSTEMI cohort, those with a LC artery occlusion had the greatest pre- and postprocedural troponin T levels. Of the patients with LC NSTEMI, 78% had Rentrop collateral grade 0 or 1 (no or minimal) flow and 22% had grade 2 or 3 (good) flow.12 No difference was seen in the 2-year mortality between patients presenting with STEMI and those present with NSTEMI in any of the 3 coronary territories (Figure 4). Discussion Our study represents one of the largest analyses correlating the angiographic finding of an acutely occluded culprit artery to the presence or absence of ST-segment eleva-
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tion on the ECG and the clinical outcomes. We observed that among patients treated invasively for a single culprit lesion in the setting of AMI, the LC artery was the least frequent culprit vessel. Also, those with a LC artery lesion were less likely to present with STEMI and hence undergo PCI with 24 hours of symptom onset than were patients with LAD or right artery occlusion. Finally, the infarct size among the NSTEMI cohort, measured as the peak troponin level, was the greatest in those with LC artery occlusion. The LC artery was the culprit vessel in approximately 20% of our cohort, a proportion similar to that seen in randomized clinical trials of patients with STEMI undergoing primary PCI.10,11,13 These trials have generally enrolled patients presenting within 12 hours of symptom onset and would not have accounted for those receiving PCI at a later point because of a delay in the diagnosis. To be more inclusive, we extended the period from AMI onset to PCI to ⱕ7 days. However, we still observed a significantly lower frequency of LC artery infarcts. Similarly, Dixon et al1 reported that the LC artery is the least frequent culprit vessel among patients with NSTEMI undergoing PCI. That the proportion was not closer to 1/3, as one might expect, might have been because of one of at least two possible reasons. First, the LC artery might be less prone to plaque rupture, leading to fewer cases of AMI. That hypothesis is based on the assumption that the geometry of the LC artery and its branches might result in more favorable vessel wall shear stress than that of LAD and right artery.1,14 However, definitive data to support this concept are lacking. Second, it is plausible that ischemic events in the distribution of the LC artery are underdiagnosed and hence these patients are less likely to be referred for PCI. This has been supported by a population-based study of randomly selected healthy persons that demonstrated that the lateral wall is equally prone to myocardial infarction compared to the other 2 coronary territories of the left ventricle when imaged by cardiac magnetic resonance imaging.15 Also, an intravascular imaging study has demonstrated that plaque rupture can occur along the entire distribution of the LC artery.16 Although most of the entire cohort presented with STEMI, 28% had NSTEMI. However, the frequency of NSTEMI presentation was significantly greater (⬃60%) for the LC artery than those with LAD or right artery occlusion (⬃20%). The greater prevalence of NSTEMI in the LC territory could not be accounted for by the protective effects of collateral circulation because the vast majority did not have good collateral flow. This is consistent with the findings from Dixon et al,1 who observed that an occluded culprit vessel was present in approximately 1/3 of those with posterolateral NSTEMI compared to only approximately 1/5 of those with infarcts at other sites. Data from the PARAGON-B (Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network) trial have also demonstrated that approximately 25% of patients with non–ST-segment elevation acute coronary syndrome have an occluded culprit artery.2 These findings can be best explained by the limited spatial resolution of the 12-lead ECG with respect to detecting ischemia/infarction on the lateral and posterior walls of the left ventricle. The current recommendation of using posterior electrocardiographic leads provides only a modest
increase in sensitivity.3,17 Isolated ST-segment depression in precordial leads (greatest in leads V2 and V3) has been suggested as a hallmark of LC occlusion, although this is not consistently present.17 A recent substudy from the Triton-Thrombolysis In Myocardial Infarction 38 trial, conducted among a population with non–ST-segment acute coronary syndrome, described the angiographic characteristic of those with isolated precordial ST-segment depression. Of the 1,198 patients, 314 (26.2%) had AMI due to an occluded vessel, of whom almost 1/2 (48.2%) were LC arteries. These patients had significantly larger infarcts and a greater combined end point of 30-day death or AMI compared to those with NSTEMI due a patent culprit vessel.18 In the present study, patients who presented with STEMI, regardless of the culprit artery, had undergone PCI within 24 hours in ⬎90% of the cases compared to approximately 50% with a NSTEMI presentation. Because patients with an occluded LC more often presented without STsegment elevation, their PCI was more likely to be delayed (Table 1). The probable under recognition and late treatment of culprit LC lesions likely results in greater myocardial damage.18 This could account for the reason that in our NSTEMI cohort, the greatest preprocedural and postprocedural troponin levels were in the LC group (Figure 3). We speculated that this reflects the inclusion of “STEMI equivalent” cases among the larger group of patients with true NSTEMI. Thus, our study results add to the growing body of evidence indicating that greater effort must be made to detect acute coronary occlusions, especially in the distribution of the LC artery. Until better strategies have been developed, we strongly recommend that posterior electrocardiographic leads should routinely be obtained in patients with ischemic symptoms and the absence of ST-segment shift or isolated precordial ST-segment depression on the 12-lead ECG. Although the data were collected prospectively, the present study was a retrospective single-center analysis and subject to the limitations of such analyses. The coronary angiograms were not all performed at presentation; hence, we could not confirm the precise timing of the culprit artery occlusion. However, in approximately 80% of our cohort, it was performed within 24 hours. We did not include patients with nonoccluded culprit arteries or multiple culprit lesions; hence, the data should not be extrapolated to all patients undergoing PCI for AMI. Core laboratory analysis of the angiograms was not performed. Data regarding collateral flow, which might have affected the electrocardiographic findings and outcomes, were not available for most patients. Core laboratory analysis of the ECG was not performed; thus, we could not analyze the magnitude of the ischemic changes in our cohort. Finally, the study was subject to referral bias because it only enrolled patients treated with PCI. Thus, we could not comment on the prevalence or outcomes in patients not diagnosed with AMI or those with AMI who were treated medically or with surgical revascularization. 1. Dixon WC IV, Wang TY, Dai D, Shunk KA, Peterson ED, Roe MT. Anatomic distribution of the culprit lesion in patients with non–STsegment elevation myocardial infarction undergoing percutaneous cor-
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onary intervention: findings from the National Cardiovascular Data Registry. J Am Coll Cardiol 2008;52:1347–1348. Wang TY, Zhang M, Fu Y, Armstrong PW, Newby LK, Gibson CM, Moliterno DJ, Van de Werf F, White HD, Harrington RA, Roe MT. Incidence, distribution, and prognostic impact of occluded culprit arteries among patients with non-ST-elevation acute coronary syndromes undergoing diagnostic angiography. Am Heart J 2009;157: 716 –723. Schmitt C, Lehmann G, Schmieder S, Karch M, Neumann FJ, Schomig A. Diagnosis of acute myocardial infarction in angiographically documented occluded infarct vessel: limitations of ST-segment elevation in standard and extended ECG leads. Chest 2001;120:1540 – 1546. Schweitzer P. The electrocardiographic diagnosis of acute myocardial infarction in the thrombolytic era. Am Heart J 1990;119:642– 654. Poh KK, Chia BL, Tan HC, Yeo TC, Lim YT. Absence of ST elevation in ECG leads V7, V8, V9 in ischaemia of non-occlusive aetiologies. Int J Cardiol 2004;97:389 –392. Krishnaswamy A, Lincoff AM, Menon V. Magnitude and consequences of missing the acute infarct-related circumflex artery. Am Heart J 2009;158:706 –712. O’Keefe JH Jr, Sayed-Taha K, Gibson W, Christian TF, Bateman TM, Gibbons RJ. Do patients with left circumflex coronary artery-related acute myocardial infarction without ST-segment elevation benefit from reperfusion therapy? Am J Cardiol 1995;75:718 –720. Matetzky S, Freimark D, Feinberg MS, Novikov I, Rath S, Rabinowitz B, Kaplinsky E, Hod H. Acute myocardial infarction with isolated ST-segment elevation in posterior chest leads V7-9: “hidden” STsegment elevations revealing acute posterior infarction. J Am Coll Cardiol 1999;34:748 –753. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the
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Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007;50:e1– e157. Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002;346:957– 966. Armstrong PW, Granger CB, Adams PX, Hamm C, Holmes D Jr, O’Neill WW, Todaro TG, Vahanian A, Van de Werf F. Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial. JAMA 2007;297:43–51. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587–592. Stone GW, Lansky AJ, Pocock SJ, Gersh BJ, Dangas G, Wong SC, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Mockel M, Ochala A, Kellock A, Parise H, Mehran R. Paclitaxeleluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med 2009;360:1946 –1959. Wang JC, Normand SL, Mauri L, Kuntz RE. Coronary artery spatial distribution of acute myocardial infarction occlusions. Circulation 2004;110:278 –284. Barbier CE, Bjerner T, Johansson L, Lind L, Ahlstrom H. Myocardial scars more frequent than expected: magnetic resonance imaging detects potential risk group. J Am Coll Cardiol 2006;48:765–771. Hong MK, Mintz GS, Lee CW, Lee BK, Yang TH, Kim YH, Song JM, Han KH, Kang DH, Cheong SS, Song JK, Kim JJ, Park SW, Park SJ. The site of plaque rupture in native coronary arteries: a three-vessel intravascular ultrasound analysis. J Am Coll Cardiol 2005;46:261– 265. Shah A, Wagner GS, Green CL, Crater SW, Sawchak ST, Wildermann NM, Mark DB, Waugh RA, Krucoff MW. Electrocardiographic differentiation of the ST-segment depression of acute myocardial injury due to the left circumflex artery occlusion from that of myocardial ischemia of nonocclusive etiologies. Am J Cardiol 1997;80:512–513. Gibson C, Pride Y, Mohanayelu S, Wiviott S, Antman E, Braunwald E. Angiographic and clinical outcomes among patients with acute coronary syndrome presenting with isolated anterior ST-segment depressions. Circulation 2008;118:S654.
0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.06.016
LC is the least frequent culprit artery among the patients enrolled.10,11 There is a paucity of data on whether the same holds true in routine clinical practice. We hypothesized that, despite the increased awareness of the difficulty of diagnosing an occluded LC artery, patients with infarcts in this territory remain less likely to undergo revascularization. Thus, the aim of the present study was to assess the incidence of LC occlusion in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), the frequency of STsegment versus non–ST segment elevation presentation among them, and to correlate the electrocardiographic findings with outcomes. Methods The study was conducted among consecutive patients who had undergone PCI from November 2001 through December 2007 with the following inclusion criteria: AMI within 7 days preceding PCI, and a single culprit vessel with either 100% occlusion or ⱖ90% stenosis with less than Thrombolysis In Myocardial Infarction 3 flow. Patients with graft conduit interventions or left main interventions or those who had undergone elective procedures were excluded. www.ajconline.org
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Table 1 Clinical, angiographic, and procedural characteristics stratified by culprit artery Variable Age (years) Men Diabetes mellitus Hypertension* Hypercholesterolemia† Body mass index (kg/m2) Chest pain before procedure Preprocedural shock Peripheral vascular disease Cerebrovascular disease Thrombolytic agents before percutaneous coronary intervention Timing of percutaneous coronary intervention ⱕ24 Hours from acute myocardial infarction ⬎24 Hours from acute myocardial infarction Single-vessel disease Angiographic presence of thrombus Preprocedural Thrombolysis In Myocardial Infarction 0 flow Stents per patient Drug-eluting stent use Thrombectomy device use Glycoprotein IIb/IIIa inhibitor use Procedural success Peak preprocedure troponin T‡ ST-segment elevation presentation Non–ST-segment elevation presentation Peak postprocedure troponin T‡ ST-segment elevation presentation Non–ST-segment elevation presentation
Right (n ⫽ 670)
LAD (n ⫽ 537)
LC (n ⫽ 293)
p Value
64.5 ⫾ 13.3 475 (71%) 107 (16%) 414 (67%) 404 (71%) 28.9 ⫾ 5.5 634 (95%) 97 (15%) 46 (7%) 59 (9%) 103 (16%)
64.4 ⫾ 13.6 370 (69%) 100 (19%) 317 (65%) 322 (70%) 29.2 ⫾ 5.8 505 (94%) 76 (14%) 29 (6%) 48 (9%) 64 (12%)
64.0 ⫾ 13.3 225 (77%) 53 (18%) 186 (69%) 182 (74%) 29.5 ⫾ 5.6 279 (95%) 39 (13%) 27 (9%) 26 (9%) 21 (7%)
0.85 0.05 0.46 0.55 0.56 0.32 0.77 0.87 0.13 0.99 0.001 ⬍0.001
539 (80%) 131 (20%) 315 (48%) 568 (90%) 425 (70%) 1.3 ⫾ 0.9 296 (44%) 72 (11%) 540 (81%) 604 (90%) 0.2 (0.0, 0.8) 0.1 (0.0, 0.6) 0.5 (0.2, 1.0) 3.2 (1.4, 6.1) 4.0 (1.9, 7.0) 1.4 (0.6, 2.7)
445 (83%) 92 (17%) 309 (59%) 426 (85%) 329 (66%) 1.2 ⫾ 0.7 214 (40%) 27 (5%) 437 (81%) 474 (88%) 0.3 (0.0, 1.3) 0.2 (0.0, 1.2) 0.5 (0.2, 1.4) 4.2 (1.5, 9.7) 5.7 (2.6, 11.5) 1.3 (0.6, 2.8)
206 (70%) 87 (30%) 137 (48%) 215 (80%) 182 (71%) 1.0 ⫾ 0.7 130 (44%) 15 (5%) 245 (84%) 250 (85%) 0.5 (0.1, 1.7) 0.2 (0.0, 1.7) 0.6 (0.2, 1.5) 3.1 (1.5, 5.9) 4.9 (2.5, 9.4) 2.5 (1.1, 4.2)
⬍0.001 ⬍0.001 0.33 ⬍0.001 0.26 ⬍0.001 0.54 0.09 ⬍0.001 ⬍0.001 0.053 ⬍0.001 ⬍0.001 ⬍0.001
* Documented history of hypertension treated with medication. † History of total cholesterol level ⬎240 mg/dl. ‡ Median (quartile 1, quartile 3). LAD ⫽ left anterior descending; LC ⫽ left circumflex.
A total of 1,566 patients with AMI who had undergone PCI for a single culprit vessel were identified. The institutional review board approved the present study. The diagnosis of AMI before PCI was determined from the final discharge diagnosis in the clinical records. To determine the accuracy of the diagnosis of STEMI versus non–STEMI (NSTEMI), one investigator (PJMB) retrospectively reviewed the preprocedural ECG to confirm the presence or absence of ST-segment elevation. STEMI was diagnosed if ⱖ1 mm of ST-segment elevation was present in 2 contiguous leads. All other patients with AMI were classified as having NSTEMI. When the ECG before revascularization was not available in the medical records (patients transferred from other hospitals), the description in the medical records from the attending cardiologist who had reviewed the ECG was used to determine the diagnosis. Blood samples for cardiac troponin T levels were collected at admission (before PCI) and 8 and 16 hours after PCI. The peak postprocedure values were used in the present analysis. A sensitive and precise third-generation assay (Elecsys, Roche Diagnostics, Indianapolis, Indiana) was used with an upper limit of normal of ⬍0.01 ng/ml (ninety-ninth percentile). The number of diseased coronary arteries was defined by the number of major arteries with ⱖ70% stenosis on visual assessment. Major adverse cardiovascular events were de-
fined as one or more of the following: in-hospital death, Q-wave myocardial infarction, the need for urgent or emergent coronary artery bypass grafting during the index hospitalization, or cerebrovascular accident, defined as transient ischemic attack or stroke. In-hospital deaths included all deaths during the index hospital admission. Procedural success was defined as a reduction of residual luminal diameter stenosis to ⬍20% without in-hospital death, Qwave myocardial infarction, or the need for emergency coronary artery bypass grafting. Long-term outcomes included all-cause mortality. Continuous variables were summarized as the mean ⫾ SD if distributed symmetrically or with mild skew and compared using one-way analysis of variance. Other continuous variables that were skewed were summarized as the median (interquartile range) and compared using the Kruskal-Wallis rank sum test. Discrete variables are presented as frequency (percentages) and were compared using Pearson’s chi-square test. Missing values were excluded from the denominator in the calculation of the percentages. Kaplan-Meier methods were used to estimate the survival rates on follow-up with comparisons tested using the log-rank test. All hypothesis tests were 2-sided with a 0.05 type I error rate. Analyses were performed using Statistical Analysis Systems, version 9.1 (SAS Institute, Cary, North Carolina).
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Figure 3. Post-PCI troponin T levels (interquartile range and median) according to culprit vessel and infarct type.
Figure 1. Relative frequency of STEMI versus NSTEMI presentation according to culprit artery.
Figure 4. Two-year mortality rates according to culprit vessel and infarct type.
Figure 2. Proportion of patients undergoing PCI within 24 hours of presentation according to culprit vessel and infarct type.
Results The baseline characteristics of the 1,500 patients with AMI are listed in Table 1, according to the culprit artery. The culprit lesion was located in the right, left anterior descending (LAD), or LC artery in 44.7%, 35.8%, and 19.5% of patients, respectively. Patients with acutely occluded LC arteries were more likely to have undergone PCI ⬎24 hours after the onset of the AMI than those with a culprit lesion in the LAD or right arteries (Table 1). In the entire cohort, the preprocedural troponin values were greater in patients with a LC occlusion. No significant difference was found in the in-hospital mortality (4.4%, 7.4%, and 6.5%, respectively; p ⫽ 0.66) or major adverse cardiovascular event (9.2%, 13.9%, and 11.6%, respectively; p ⫽ 0.53) rates for patients with right, LAD, and LC occlusions. A total of 1,077 patients (72%) presented with STEMI and 423 (28%) presented with NSTEMI. Figure 1 demonstrates the relative frequency of STEMI versus NSTEMI
presentation according to the culprit artery. Only 127 patients (12%) with STEMI had a culprit lesion in the LC artery compared to 166 patients (39%) presenting with NSTEMI. Figure 2 illustrates the proportion of patients undergoing PCI within 24 hours of presentation according to the culprit vessel and infarct type. PCI was performed within 24 hours in 957 (89%) of 1,077 patients presenting with STEMI and 233 (55%) of the 423 patients presenting with NSTEMI. The pre- and postprocedural troponin T levels according to the culprit vessel and infarct type are summarized in Figure 3 and Table 1. Of the NSTEMI cohort, those with a LC artery occlusion had the greatest pre- and postprocedural troponin T levels. Of the patients with LC NSTEMI, 78% had Rentrop collateral grade 0 or 1 (no or minimal) flow and 22% had grade 2 or 3 (good) flow.12 No difference was seen in the 2-year mortality between patients presenting with STEMI and those present with NSTEMI in any of the 3 coronary territories (Figure 4). Discussion Our study represents one of the largest analyses correlating the angiographic finding of an acutely occluded culprit artery to the presence or absence of ST-segment eleva-
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tion on the ECG and the clinical outcomes. We observed that among patients treated invasively for a single culprit lesion in the setting of AMI, the LC artery was the least frequent culprit vessel. Also, those with a LC artery lesion were less likely to present with STEMI and hence undergo PCI with 24 hours of symptom onset than were patients with LAD or right artery occlusion. Finally, the infarct size among the NSTEMI cohort, measured as the peak troponin level, was the greatest in those with LC artery occlusion. The LC artery was the culprit vessel in approximately 20% of our cohort, a proportion similar to that seen in randomized clinical trials of patients with STEMI undergoing primary PCI.10,11,13 These trials have generally enrolled patients presenting within 12 hours of symptom onset and would not have accounted for those receiving PCI at a later point because of a delay in the diagnosis. To be more inclusive, we extended the period from AMI onset to PCI to ⱕ7 days. However, we still observed a significantly lower frequency of LC artery infarcts. Similarly, Dixon et al1 reported that the LC artery is the least frequent culprit vessel among patients with NSTEMI undergoing PCI. That the proportion was not closer to 1/3, as one might expect, might have been because of one of at least two possible reasons. First, the LC artery might be less prone to plaque rupture, leading to fewer cases of AMI. That hypothesis is based on the assumption that the geometry of the LC artery and its branches might result in more favorable vessel wall shear stress than that of LAD and right artery.1,14 However, definitive data to support this concept are lacking. Second, it is plausible that ischemic events in the distribution of the LC artery are underdiagnosed and hence these patients are less likely to be referred for PCI. This has been supported by a population-based study of randomly selected healthy persons that demonstrated that the lateral wall is equally prone to myocardial infarction compared to the other 2 coronary territories of the left ventricle when imaged by cardiac magnetic resonance imaging.15 Also, an intravascular imaging study has demonstrated that plaque rupture can occur along the entire distribution of the LC artery.16 Although most of the entire cohort presented with STEMI, 28% had NSTEMI. However, the frequency of NSTEMI presentation was significantly greater (⬃60%) for the LC artery than those with LAD or right artery occlusion (⬃20%). The greater prevalence of NSTEMI in the LC territory could not be accounted for by the protective effects of collateral circulation because the vast majority did not have good collateral flow. This is consistent with the findings from Dixon et al,1 who observed that an occluded culprit vessel was present in approximately 1/3 of those with posterolateral NSTEMI compared to only approximately 1/5 of those with infarcts at other sites. Data from the PARAGON-B (Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network) trial have also demonstrated that approximately 25% of patients with non–ST-segment elevation acute coronary syndrome have an occluded culprit artery.2 These findings can be best explained by the limited spatial resolution of the 12-lead ECG with respect to detecting ischemia/infarction on the lateral and posterior walls of the left ventricle. The current recommendation of using posterior electrocardiographic leads provides only a modest
increase in sensitivity.3,17 Isolated ST-segment depression in precordial leads (greatest in leads V2 and V3) has been suggested as a hallmark of LC occlusion, although this is not consistently present.17 A recent substudy from the Triton-Thrombolysis In Myocardial Infarction 38 trial, conducted among a population with non–ST-segment acute coronary syndrome, described the angiographic characteristic of those with isolated precordial ST-segment depression. Of the 1,198 patients, 314 (26.2%) had AMI due to an occluded vessel, of whom almost 1/2 (48.2%) were LC arteries. These patients had significantly larger infarcts and a greater combined end point of 30-day death or AMI compared to those with NSTEMI due a patent culprit vessel.18 In the present study, patients who presented with STEMI, regardless of the culprit artery, had undergone PCI within 24 hours in ⬎90% of the cases compared to approximately 50% with a NSTEMI presentation. Because patients with an occluded LC more often presented without STsegment elevation, their PCI was more likely to be delayed (Table 1). The probable under recognition and late treatment of culprit LC lesions likely results in greater myocardial damage.18 This could account for the reason that in our NSTEMI cohort, the greatest preprocedural and postprocedural troponin levels were in the LC group (Figure 3). We speculated that this reflects the inclusion of “STEMI equivalent” cases among the larger group of patients with true NSTEMI. Thus, our study results add to the growing body of evidence indicating that greater effort must be made to detect acute coronary occlusions, especially in the distribution of the LC artery. Until better strategies have been developed, we strongly recommend that posterior electrocardiographic leads should routinely be obtained in patients with ischemic symptoms and the absence of ST-segment shift or isolated precordial ST-segment depression on the 12-lead ECG. Although the data were collected prospectively, the present study was a retrospective single-center analysis and subject to the limitations of such analyses. The coronary angiograms were not all performed at presentation; hence, we could not confirm the precise timing of the culprit artery occlusion. However, in approximately 80% of our cohort, it was performed within 24 hours. We did not include patients with nonoccluded culprit arteries or multiple culprit lesions; hence, the data should not be extrapolated to all patients undergoing PCI for AMI. Core laboratory analysis of the angiograms was not performed. Data regarding collateral flow, which might have affected the electrocardiographic findings and outcomes, were not available for most patients. Core laboratory analysis of the ECG was not performed; thus, we could not analyze the magnitude of the ischemic changes in our cohort. Finally, the study was subject to referral bias because it only enrolled patients treated with PCI. Thus, we could not comment on the prevalence or outcomes in patients not diagnosed with AMI or those with AMI who were treated medically or with surgical revascularization. 1. Dixon WC IV, Wang TY, Dai D, Shunk KA, Peterson ED, Roe MT. Anatomic distribution of the culprit lesion in patients with non–STsegment elevation myocardial infarction undergoing percutaneous cor-
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