Prevalence and Long-term Outcomes of Patients with Coronary Artery Ectasia Presenting with Acute Myocardial Infarction

Abstract

Coronary artery ectasia (CAE) is described in 5% of patients undergoing coronary angiography. Previous studies have shown controversial results regarding the prognostic impact of CAE. The prevalence and prognostic value of CAE in patients with acute myocardial infarction (AMI) remain unknown. In 4788 patients presenting with AMI referred for coronary angiography the presence of CAE (defined as dilation of a coronary segment with a diameter ≥1.5 times of the adjacent normal segment) was confirmed in 174 (3.6%) patients (age 62 ± 12 years; 81% male), and was present in the culprit vessel in 79.9%. Multivessel CAE was frequent (67%). CAE patients were more frequently male, had high thrombus burden and were treated more often with thrombectomy and less often was stent implantation. Markis I was the most frequent angiographic phenotype (43%). During a median follow-up of 4 years (1-7), 1243 patients (26%) experienced a major adverse cardiovascular event (MACE): 282 (6%) died from a cardiac cause, 358 (8%) had a myocardial infarction, 945 (20%) underwent coronary revascularization and 58 (1%) presented with a stroke. Patients with CAE showed higher rates of MACE as compared to those without CAE (36.8% versus 25.6%; p <0.001). On multivariable analysis, CAE was associated with MACE (HR 1.597; 95% CI 1.238-2.060; p <0.001) after adjusting for risk factors, type of AMI and number of narrowed coronary arteries. In conclusion, the prevalence of CAE in patients presenting with AMI is relatively low but was independently associated with an increased risk of MACE at follow-up. Coronary artery ectasia (CAE) is described in 5% of patients undergoing coronary angiography. Previous studies have shown controversial results regarding the prognostic impact of CAE. The prevalence and prognostic value of CAE in patients with acute myocardial infarction (AMI) remain unknown. In 4788 patients presenting with AMI referred for coronary angiography the presence of CAE (defined as dilation of a coronary segment with a diameter ≥1.5 times of the adjacent normal segment) was confirmed in 174 (3.6%) patients (age 62 ± 12 years; 81% male), and was present in the culprit vessel in 79.9%. Multivessel CAE was frequent (67%). CAE patients were more frequently male, had high thrombus burden and were treated more often with thrombectomy and less often was stent implantation. Markis I was the most frequent angiographic phenotype (43%). During a median follow-up of 4 years (1-7), 1243 patients (26%) experienced a major adverse cardiovascular event (MACE): 282 (6%) died from a cardiac cause, 358 (8%) had a myocardial infarction, 945 (20%) underwent coronary revascularization and 58 (1%) presented with a stroke. Patients with CAE showed higher rates of MACE as compared to those without CAE (36.8% versus 25.6%; p <0.001). On multivariable analysis, CAE was associated with MACE (HR 1.597; 95% CI 1.238-2.060; p <0.001) after adjusting for risk factors, type of AMI and number of narrowed coronary arteries. In conclusion, the prevalence of CAE in patients presenting with AMI is relatively low but was independently associated with an increased risk of MACE at follow-up. Coronary artery ectasia (CAE) is defined as a dilation of a coronary artery segment with at least 1.5 times the diameter of the adjacent normal segments.1Ruiz-Morales JM González-Chon O García-López SMdC Coronary artery ectasia prevalence and clinical characteristics: experience from a single medical center.Médica Sur. 2018; 20: 208-213Google Scholar The prevalence of CAE in patients undergoing coronary angiography ranges from 0.3% to 5.3% .2Swaye PS Fisher LD Litwin P Vignola PA Judkins MP Kemp HG Mudd JG Gosselin AJ Aneurysmal coronary artery disease.Circulation. 1983; 67: 134-138Crossref PubMed Scopus (775) Google Scholar CAE may be detected as an incidental finding in asymptomatic patients during coronary angiography (i.e. prior to valve surgery or atrial fibrillation ablation) or in the context of an acute myocardial infarction (AMI).3Cohen P O'Gara PT Coronary artery aneurysms: a review of the natural history, pathophysiology, and management.Cardiol Rev. 2008; 16: 301-304Crossref PubMed Scopus (114) Google Scholar Clinical symptoms could be caused by the presence of concomitant obstructive atherosclerotic disease or distal embolization due to local thrombosis in the lumen of a large aneurysmatic coronary segment.4Rath S Har-Zahav Y Battler A Agranat O Rotstein Z Rabinowitz B Neufeld HN Fate of nonobstructive aneurysmatic coronary artery disease: angiographic and clinical follow-up report.Am Heart J. 1985; 109: 785-791Crossref PubMed Scopus (131) Google Scholar In patients presenting with AMI, the presence of CAE may influence the procedural success and the long-term outcome. However, current knowledge is based on small sample size studies which showed contradictory results.5Hartnell G Parnell B Pridie R Coronary artery ectasia. Its prevalence and clinical significance in 4993 patients.Heart. 1985; 54: 392-395Crossref Scopus (398) Google Scholar, 6Zhang Y Huang Q-J Li X-L Guo Y-L Zhu C-G Wang X-W Xu B Gao R-L Li J-J Prognostic value of coronary artery stenoses, markis class, and ectasia ratio in patients with coronary artery ectasia.Cardiology. 2015; 131: 251-259Crossref PubMed Scopus (13) Google Scholar, 7Baman TS Cole JH Devireddy CM Sperling LS Risk factors and outcomes in patients with coronary artery aneurysms.Am J Cardiol. 2004; 93: 1549-1551Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar, 8Kawsara A Gil IJN Alqahtani F Moreland J Rihal CS Alkhouli M Management of coronary artery aneurysms.JACC: Cardiovasc Intervent. 2018; 11: 1211-1223Crossref PubMed Scopus (87) Google Scholar, 9Doi T Kataoka Y Noguchi T Shibata T Nakashima T Kawakami S Nakao K Fujino M Nagai T Kanaya T Coronary artery ectasia predicts future cardiac events in patients with acute myocardial infarction.Arterioscler Thromb Vasc Biol. 2017; 37: 2350-2355Crossref PubMed Scopus (40) Google Scholar Accordingly, we aimed at: 1) assessing the prevalence of CAE in a large cohort of patients presenting with AMI, 2) defining the main phenotypical angiographic characteristics of patients with and without CAE and 3) at investigating the long-term prognostic impact of CAE. Consecutive patients presenting with AMI at the Leiden University Medical Center (Leiden, the Netherlands) between February 2004 to October 2015, who underwent acute invasive coronary angiography, were included in the analysis. Patients with previous history of coronary artery bypass grafting were excluded. Invasive coronary angiography was performed in a standard fashion and revascularization of the culprit lesion was performed according to contemporary recommendations. Patients were subsequently treated according to the institutional protocol,10Liem SS van der Hoeven BL Oemrawsingh PV Bax JJ van der Bom JG Bosch J Viergever EP van Rees C Padmos I Sedney MI van Exel HJ Verwey HF Atsma DE van der Velde ET Jukema JW van der Wall EE Schalij MJ MISSION!: optimization of acute and chronic care for patients with acute myocardial infarction.Am Heart J. 2007; 153 (e11-11): 14Crossref PubMed Scopus (113) Google Scholar remaining hospitalized for at least 48 hours. Baseline demographic and clinical data, including cardiovascular risk factors and medications at discharge, were retrospectively collected from the Departmental Cardiology Information System (EPD-Vision: Leiden University Medical Center, Leiden, The Netherlands). This retrospective study of clinically acquired data was approved by the Institutional Review Board and the need for patient written informed consent was waived. CAE was defined as a dilation of a coronary artery segment with a diameter ≥1.5 times of the adjacent normal segment. Patients with CAE in any of the coronary vessels during index coronary angiography were identified. The study cohort was divided into two groups, according to the presence or absence of CAE. Coronary angiograms obtained during the index procedure were retrospectively evaluated by two independent interventional cardiologists blinded to the clinical outcomes. The angiographic anatomical distribution of CAE was categorized according to the Markis classification11Markis JE Joffe CD Cohn PF Feen DJ Herman MV Gorlin R Clinical significance of coronary arterial ectasia.Am J Cardiol. 1976; 37: 217-222Abstract Full Text PDF PubMed Scopus (433) Google Scholar: type I was defined as the presence of diffuse CAE in 2 or 3 coronary vessels; type II as diffuse CAE in one coronary vessel and localized CAE in another vessel; type III as diffuse CAE in only one coronary vessel and type IV as localized or segmental CAE (Figure 1). Multivessel disease was defined by the presence of a coronary stenosis >50% in ≥2 major coronary arteries. Coronary artery flow was evaluated by using the Thrombolysis In Myocardial Infarction (TIMI) frame count method.12Gibson CM Cannon CP Daley WL Dodge Jr., JT Alexander Jr., B Marble SJ McCabe CH Raymond L Fortin T Poole WK Braunwald E TIMI frame count: a quantitative method of assessing coronary artery flow.Circulation. 1996; 93: 879-888Crossref PubMed Scopus (1496) Google Scholar Thrombus burden was graded from 0 to 5 according to the TIMI-thrombus scale.13Sianos G Papafaklis MI Daemen J Vaina S van Mieghem CA van Domburg RT Michalis LK Serruys PW Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden.J Am Coll Cardiol. 2007; 50: 573-583Crossref PubMed Scopus (395) Google Scholar High thrombus burden was defined as a TIMI-thrombus scale ≥4. Angiographic success was defined as final TIMI 3 distal flow with less than 20% of vessel stenosis and no immediate mechanical complications. No-reflow phenomenon was defined as TIMI flow ≤2 at the end of the procedure without angiographic evidence of mechanical vessel obstruction.14Morishima I Sone T Mokuno S Taga S Shimauchi A Oki Y Kondo J Tsuboi H Sassa H Clinical significance of no-reflow phenomenon observed on angiography after successful treatment of acute myocardial infarction with percutaneous transluminal coronary angioplasty.Am Heart J. 1995; 130: 239-243Crossref PubMed Scopus (171) Google Scholar Patients were followed-up according to the institutional guideline-based care-track protocol.10Liem SS van der Hoeven BL Oemrawsingh PV Bax JJ van der Bom JG Bosch J Viergever EP van Rees C Padmos I Sedney MI van Exel HJ Verwey HF Atsma DE van der Velde ET Jukema JW van der Wall EE Schalij MJ MISSION!: optimization of acute and chronic care for patients with acute myocardial infarction.Am Heart J. 2007; 153 (e11-11): 14Crossref PubMed Scopus (113) Google Scholar The primary endpoint was composite of major adverse cardiovascular events (MACE) which included cardiac death, myocardial infarction, stroke and repeated coronary revascularization, including percutaneous coronary intervention or coronary artery bypass grafting. Secondary endpoints were the individual components of the composite outcome. Deaths were considered to be attributable to a cardiac cause unless a noncardiac death could be confirmed. Myocardial infarction was defined as an increase of cardiac troponin with at least 1 value above the 99th percentile upper reference limit and ischemic symptoms and/or new or presumed new ST‐segment, T‐wave changes or new left bundle branch block.15Thygesen K Alpert JS Jaffe AS Chaitman BR Bax JJ Morrow DA White HD Executive Group on behalf of the Joint European Society of Cardiology /American College of Cardiology /American Heart Association /World Heart Federation Task Force for the Universal Definition of Myocardial IFourth Universal Definition of Myocardial Infarction (2018).J Am Coll Cardiol. 2018; 72: 2231-2264Crossref PubMed Scopus (1012) Google Scholar Stroke was defined as any cerebrovascular event (intracranial hemorrhage or non-hemorrhagic stroke) meeting the following criteria: 1) rapid onset of neurological deficit; 2) duration ≥24 hours or <24 hours if therapeutic intervention, neuro-imaging or death; 3) absence of non-stroke cause; 4) confirmation by neurologist/neurosurgeon, neuro-imaging or lumbar puncture. Medical records review and survival status information were obtained through the hospital information systems (EPD-Vision and EZIS; Leiden University Medical Centre, Leiden, The Netherlands). Normally distributed continuous variables are presented as mean ± standard deviation while non-normally distributed continuous variables are presented as median with interquartile range. Categorical data are presented as numbers and percentages. Unpaired Student's t-test was used for comparison of normally distributed continuous variables, Mann-Whitney U test for non-normally distributed continuous variables, and chi-square test for categorical data. The cumulative events were calculated using the Kaplan–Meier curves and comparison between groups was performed using the log-rank test. Uni- and multivariable Cox regression analyses were performed to identify independent demographic, clinical and angiographic variables associated with MACE. The hazard ratio (HR) and 95% confidence interval are presented. All statistical tests were two-sided, and a P-value <0.05 was considered statistically significant. Data analyses were performed using SPSS version 25.0 software (IBM SPSS Statistics for Windows. Armonk, NY, 4788 patients years CAE was observed in 174 (3.6%) Baseline characteristics of patients with and without CAE are shown in Patients with CAE were more frequently as compared to patients without CAE. were no in clinical Angiographic and procedural data are in distribution of the culprit the coronary artery was the most frequent culprit vessel in patients with in patients without the left was the most was more often used in patients with CAE the of stent in the culprit lesion was than in those patients with CAE were treated with stents of as compared to patients without clinical ± ± ± ± ± ± at ± ± ± ± ± ± ± ± ± at II left myocardial percutaneous coronary ST-segment elevation myocardial in myocardial in a new and procedural lesion of narrowed coronary of diameter TIMI flow TIMI flow TIMI flow Thrombolysis in Myocardial in a new II left myocardial percutaneous coronary ST-segment elevation myocardial in myocardial Thrombolysis in Myocardial The angiographic characteristics of patients with CAE are in CAE was observed in the by the left artery and left main coronary CAE was present in the culprit vessel in the of the presence of CAE frequently thrombus burden was present in of CAE was according to the by Markis JE Joffe CD Cohn PF Feen DJ Herman MV Gorlin R Clinical significance of coronary arterial ectasia.Am J Cardiol. 1976; 37: 217-222Abstract Full Text PDF PubMed Scopus (433) Google Scholar patients were as type I CAE in 2 or 3 coronary as type II CAE in 1 vessel and localized CAE in another as type III CAE in only 1 and as type IV or segmental angiographic of patients with coronary artery coronary in single vessel of CAE according to Markis thrombus coronary artery ectasia. in a new coronary artery ectasia. During a median follow-up of 4 years 1243 patients (26%) presented with MACE. The individual components of MACE as 282 patients (6%) died from a cardiac cause, 358 (8%) had a myocardial infarction, 945 (20%) underwent coronary revascularization and 58 (1%) a stroke. The distribution of events in patients with and without CAE is presented in showed higher rates of MACE in patients with CAE compared with those without CAE (Figure were no between groups regarding cardiac death and myocardial were between groups in of any revascularization and as in survival curves of cumulative MACE in patients with CAE versus patients without CAE CAE coronary artery MACE major adverse cardiovascular survival curves of cumulative of cardiac death; revascularization and stroke in patients with CAE versus patients without CAE CAE coronary artery MI myocardial the between CAE and the of and multivariable Cox regression analyses were performed On analysis, previous myocardial infarction, ST-segment elevation myocardial infarction at coronary artery final TIMI flow and CAE showed a with MACE. On multivariable analysis, previous at coronary artery TIMI flow and CAE independently associated with and multivariable to the between CAE and 95% 95% one one at coronary artery TIMI flow one of coronary artery left major adverse cardiovascular myocardial ST-segment elevation Thrombolysis in Myocardial in a new coronary artery left major adverse cardiovascular myocardial ST-segment elevation Thrombolysis in Myocardial The prevalence of CAE in a large cohort of patients presenting with AMI was Patients with CAE presented with ectasia 2 or more coronary in CAE in the culprit vessel was in of of the study Patients with CAE presenting with AMI had an increased of MACE at follow-up compared with those without CAE. This was independent from cardiovascular risk factors, type of AMI and number of The of CAE and have A Gil IJN Alqahtani F Moreland J Rihal CS Alkhouli M Management of coronary artery aneurysms.JACC: Cardiovasc Intervent. 2018; 11: 1211-1223Crossref PubMed Scopus (87) Google Scholar the frequent of CAE with obstructive to CAE and a PS Fisher LD Litwin P Vignola PA Judkins MP Kemp HG Mudd JG Gosselin AJ Aneurysmal coronary artery disease.Circulation. 1983; 67: 134-138Crossref PubMed Scopus (775) Google CD E The natural history of coronary artery PubMed Scopus Google A J R Coronary artery clinical and angiographic characteristics and Cardiol. Google Scholar In have to as and MP A Coronary artery Rev. 2008; 16: PubMed Scopus Google E J into an Cardiol. 2007; PubMed Scopus Google Scholar CAE with and of A Gil IJN Alqahtani F Moreland J Rihal CS Alkhouli M Management of coronary artery aneurysms.JACC: Cardiovasc Intervent. 2018; 11: 1211-1223Crossref PubMed Scopus (87) Google Scholar Previous studies have a prevalence of CAE from 0.3% to 5.3% in patients undergoing coronary PS Fisher LD Litwin P Vignola PA Judkins MP Kemp HG Mudd JG Gosselin AJ Aneurysmal coronary artery disease.Circulation. 1983; 67: 134-138Crossref PubMed Scopus (775) Google G Parnell B Pridie R Coronary artery ectasia. Its prevalence and clinical significance in 4993 patients.Heart. 1985; 54: 392-395Crossref Scopus (398) Google CD E The natural history of coronary artery PubMed Scopus Google A I Coronary and results of coronary bypass Heart J. PubMed Scopus Google Scholar to in a study including patients with ischemic disease from S U S H S K M M Coronary in and patients with disease: a Heart J. Google Scholar of the Coronary which patients who underwent coronary angiography, CAE was in PS Fisher LD Litwin P Vignola PA Judkins MP Kemp HG Mudd JG Gosselin AJ Aneurysmal coronary artery disease.Circulation. 1983; 67: 134-138Crossref PubMed Scopus (775) Google Scholar However, are data regarding the prevalence of CAE in patients presenting with The presence of CAE in the culprit vessel in studies with sample M Clinical and of coronary artery in patients with acute myocardial infarction undergoing a primary percutaneous coronary PubMed Scopus Google Scholar CAE in the culprit vessel in of a cohort of in another study of patients with myocardial infarction, the of CAE was H A S M of primary percutaneous intervention in patients with coronary artery PubMed Scopus Google Scholar The results of the present with 5 times previous and a of CAE of of and the presence of CAE in the culprit the angiographic CAE the in the of This higher of the to CAE as compared to the coronary PS Fisher LD Litwin P Vignola PA Judkins MP Kemp HG Mudd JG Gosselin AJ Aneurysmal coronary artery disease.Circulation. 1983; 67: 134-138Crossref PubMed Scopus (775) Google Scholar but the unknown. In CAE is and described in only of patients with CD E The natural history of coronary artery PubMed Scopus Google Scholar This is to the present CAE was observed in of the patients and the Markis type I the most frequently anatomical phenotype This be by the characteristics of the study versus A large thrombus burden and a low TIMI flow was observed in patients with which is with previous M Clinical and of coronary artery in patients with acute myocardial infarction undergoing a primary percutaneous coronary PubMed Scopus Google G B T M O MI A O Risk factors and outcomes in patients with artery who underwent primary percutaneous coronary intervention after myocardial Cardiovasc PubMed Scopus Google Scholar A large thrombus burden may from a coronary flow and a flow to and thrombus in the of the coronary Cardiovasc Full Text PDF PubMed Google Scholar in patients with CAE by obstructive coronary artery the of and coronary may coronary flow S of in coronary artery caused by 11: PubMed Scopus Google Scholar the of atherosclerotic Thrombus was subsequently more often used in patients with CAE. Thrombus in acute myocardial infarction shown to distal embolization and coronary myocardial and T van der van AJ Thrombus during primary percutaneous coronary J 2008; PubMed Scopus Google Scholar However, thrombus and have frequently used in patients with AMI and the of no-reflow or distal embolization is G B T M O MI A O Risk factors and outcomes in patients with artery who underwent primary percutaneous coronary intervention after myocardial Cardiovasc PubMed Scopus Google Y after primary percutaneous coronary intervention for myocardial infarction caused by 2017; Full Text Full Text PDF PubMed Scopus Google Scholar observed a higher of final TIMI flow in patients with CAE compared to In the present patients with CAE were less often treated with stent compared with and stents were coronary intervention for lesion in coronary in the of AMI is associated with a higher of procedural and a higher of adverse Y after primary percutaneous coronary intervention for myocardial infarction caused by 2017; Full Text Full Text PDF PubMed Scopus Google U Y M T stent a coronary in a patient with disease: with Cardiovasc Intervent. 2017; PubMed Scopus Google Scholar of stent according to the size and of CAE is to the risk of stent thrombosis and stent may be for the of the lumen diameter and K M H Y Y S Y S H T of patients with disease by coronary aneurysms: a PubMed Scopus Google Scholar Previous studies have shown results on the prognostic impact of CAE. In the the presence of CAE showed no on survival at after adjusting for PS Fisher LD Litwin P Vignola PA Judkins MP Kemp HG Mudd JG Gosselin AJ Aneurysmal coronary artery disease.Circulation. 1983; 67: 134-138Crossref PubMed Scopus (775) Google CD E The natural history of coronary artery PubMed Scopus Google Scholar In a retrospective study of patients with CAE risk of MACE at compared to a without CD E The natural history of coronary artery PubMed Scopus Google Scholar However, patients undergoing coronary angiography, showed the presence of CAE was associated with compared to those without CAE. In patients with AMI, we observed the presence of CAE was associated to a MACE compared to patients without CAE. be by the characteristics of the study and the of CAE in is no on the therapeutic to CAE which may clinical outcomes. in be This is a retrospective of clinically acquired data, with the associated to the of the Patients with previous coronary artery bypass surgery were which may a of thrombus burden according to the TIMI thrombus scale was only performed in patients with CAE. coronary intervention optimization with was which may have on the procedural outcome. to the relatively small sample size of patients with of the between CAE and MACE be excluded. In conclusion, the prevalence of CAE in patients presenting with AMI was The presence of CAE was independently associated with an increased risk of MACE at follow-up. This was independent from cardiovascular risk factors, type of AMI and number of Xu Wang is by a from the University of The of Cardiology of the Leiden University Medical Center from and from from and and J Bax from from and and from and of the The remaining have to

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