Original Research Received: September 3, 2014 Accepted after revision: March 16, 2015 Published online: May 12, 2015
Cardiology 2015;131:251–259 DOI: 10.1159/000381702
Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia Yan Zhang a Qiao-Juan Huang a, b Xiao-Lin Li a Yuan-Lin Guo a Cheng-Gang Zhu a Xiao-Wei Wang c Bo Xu a Run-Lin Gao a Jian-Jun Li a
a
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, b Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, and c Kenli County Hospital, Shandong, China
Abstract Objectives: To assess the prognostic value of coexisting coronary artery disease (CAD), Markis class, and ectasia ratio for major adverse cardiovascular events in patients with coronary artery ectasia (CAE). Methods: A total of 512 consecutive patients with angiographically proven CAE were enrolled. Coronary ectasia extent was graded using the Markis class, and ectasia severity was assessed based on the ectasia ratio. Patients were followed up for a median of 34.6 months. Results: In the current study, 76 cases had isolated CAE, while the remaining 436 cases had coexisting CAD (mixture CAE). Males (84.4%) were predominantly affected, and the right coronary artery (55.1%) was most commonly involved. During follow-up, 86 overall major adverse cardiovascular events were diagnosed. Kaplan-Meier analysis failed to reveal any differences between isolated and mixture CAE in both cumulative and event-free survival analyses (p = 0.429 and p = 0.277, respectively). Moreover, when patients were divided into 4 groups according to Markis class (type I–IV) or
© 2015 S. Karger AG, Basel 0008–6312/15/1314–0251$39.50/0 E-Mail [email protected] www.karger.com/crd
2 groups based on the ectasia ratio (1.5–2.0 and >2.0), there was no significant difference in survival outcomes among the groups (p > 0.05). Conclusions: In this follow-up study with a relatively large sample, the survival rate of patients with CAE appeared to be independent of coexisting CAD and ectasia extent and severity. © 2015 S. Karger AG, Basel
Introduction
Coronary artery ectasia (CAE) has been defined as localized or diffuse dilation of coronary arteries exceeding 1.5-fold the diameter of the adjacent normal segment on coronary angiography [1]. CAE is a relatively rare abnormality of the coronary arterial tree and it is considered to be detected in 0.3–5.3% of consecutive angiographic series [2, 3]. The etiopathogenesis of CAE is completely unclear and more than half of the cases have been reported to be associated with coronary atherosclerosis. Furthermore, CAE has been reported to be linked to various con-
Y.Z. and Q.-J.H. contributed equally to this study.
Jian-Jun Li, MD, PhD, Division of Dyslipidemia State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences Peking Union Medical College, Beilishi Road 167, Beijing 100037 (China) E-Mail lijianjun938 @ 126.com
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Key Words Coronary artery ectasia · Coronary artery disease · Coronary angiography
Methods Study Population The study population was selected among 42,800 consecutive patients who underwent coronary angiography from May 2006 to August 2010 at our institution. As shown in figure 1, a total of 512 eligible consecutive patients with documented CAE were enrolled into the current study. For identification of patients with CAE, all patients with the terms ‘coronary ectasia’ or ‘coronary aneurysm’ in their catheterization reports were selected. Our study complied with the Declaration of Helsinki and was approved by the hospital ethics review board (Fu Wai Hospital and the National Center for Cardiovascular Diseases, Beijing, China). Information regarding traditional cardiovascular risk factors and symptoms as well as clinical findings was collected from medical records. In patients with typical symptoms, angina was assessed according to the Canadian Cardiovascular Society classifi-
252
Cardiology 2015;131:251–259 DOI: 10.1159/000381702
cation [18]. Hypertension was diagnosed according to repeated blood pressure measurements ≥140/90 mm Hg and/or consumption of antihypertensive drugs. Diabetes mellitus was diagnosed as fasting serum glucose levels ≥7.0 mmol/l in multiple determinations or if patients were being treated with insulin or oral hypoglycemic agents. Hyperlipidemia was considered to be present in patients with fasting total cholesterol ≥5.18 mmol/l or triglyceride ≥1.70 mmol/l. Current smoking was defined as having a history of cigarette smoking within the past year. CAD was defined as the presence of obstructive lesions >50% in at least 1 of the 3 major coronary arteries or major branches assessed by at least 2 independent senior interventional cardiologists. Unstable angina pectoris was defined as: new-onset angina within 2 months after a previous bout; angina with a progressive crescendo pattern, with the anginal episodes increasing in frequency and/or duration, and angina that occurred at rest [19]. Coronary Angiographic Evaluation A conventional coronary angiography was performed in all patients using Judkin’s technique. After obtaining images by standard approaches, each angiogram was interpreted by at least 2 independent cardiologists. The reference vessel was considered the most proximal part of the coronary artery that did not display any angiographic evidence of stenosis or abrupt ectasia. The maximum width of each ecstatic segment was measured in the view in which it appeared largest. The diagnosis of CAE was made according to standard criteria with a ratio of at least 1.5 [1]. Patients were considered to have isolated or mixture CAE according to the following criteria: isolated CAE (fig. 2a, b) was defined as no evidence of coronary stenosis, while mixture CAE (fig. 2c, d) was defined as angiographic evidence of CAD in addition to the dilated segment. Ectasia extent was evaluated and categorized according to Markis class [20]. Traditionally, the classification of Markis classes was as follows: (1) diffuse ectasia with ectatic lesions in two vessels (type I), (2) diffuse ectasia in one vessel and discrete ectasia in another (type II), (3) diffuse ectasia in one vessel (type III), and (4) discrete ectasia in one vessel (type IV). Ectasia severity was assessed based on the ectasia ratio (the diameter of the ectactic segment of the adjacent normal segment). According to the ectasia ratio, ectasias were divided into 2 groups: ectasias with a 1.5- to 2.0-fold increase and ecstasias with a more than 2.0-fold increase compared to the normal vessel diameter. The most frequent reasons for exclusion were: (1) patients with coronary stenosis that was so severe that the normal coronary reference diameter could not be determined, (2) patients with ectactic segments appearing within or directly associated with a coronary bypass graft, (3) patients with an ectactic segment in an area of previous percutaneous revascularization, (4) patients with CAE directly involving branching of coronary vessels, and (5) patients with valve (including mitral valve prolapse) or congenital heart disease or cardiomyopathy which may influence cardiac function evaluation. The design of this study and the complete inclusion/ exclusion criteria are displayed in figure 1. Follow-Up Follow-up data were obtained via standardized telephone interviews conducted by study nurses who were blinded to the aim of this study, after 24, 48, and 60 months. If patients reported that they had been hospitalized, appropriate hospital records were consulted. The primary endpoints were the composite of death, nonfatal acute myo-
Zhang/Huang/Li/Guo/Zhu/Wang/Xu/ Gao/Li
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ditions such as congenital abnormalities and inflammatory and connective tissue disorders [4–6]. The clinical significance of CAE remains poorly defined, and conflicting results have been reported. Due to its frequent coexistence with obstructive coronary artery disease (CAD), it has been considered to be a variant of coronary atherosclerotic disease [1, 7]. Several studies have found its clinical expression and long-term cardiac events to be mostly associated with the severity of stenotic coronary lesions, suggesting that isolated ectasia may be associated with a good prognosis at follow-up [1, 8, 9]. Nevertheless, multiple investigations have documented that CAE is not an innocent condition. Even in the absence of obstructive CAD, patients with CAE may still present with ischemia as well as acute coronary syndrome due to coronary spasm, a slow blood flow, platelet aggregation, thrombus formation, and so forth [10–15]. However, because of the low incidence of CAE in the general population, only a small number of patients can be enrolled into follow-up studies. Therefore, reliable data regarding long-term outcomes and evaluating the underlying impact factors of CAE are scarce. To date, the extent and severity of CAE are usually assessed based on the topographical extent of ectasia [16] (Markis class) and the ectasia ratio [17], respectively, which have been proved to be related to decreased thrombosis in myocardial infarction (TIMI) frame counts [11, 17]. However, the associations of the extent and severity of CAE with clinical outcomes have not been fully examined over a relatively long-term follow-up period. Thus, the aim of the present study was to evaluate the impact of 3 predictive fashions including coexisting CAD, Markis class, and ectasia ratio on the outcomes of CAE in a relatively large Chinese cohort.
Inclusion criteria: • Angiographically documented CAE • Men and women over 18 years of age • Written informed consent
Consecutive patients screened: n = 42,800
Exclusion criteria: • Coronary stenosis so severe that the normal coronary diameter could not be determined
Angiographically proven CAE: n = 556
• Ectactic segments within or associated with previous revascularization or directly involving the branch of coronary vessels • Valvular, congenital heart disease or cardiomyopathy
Eligible sample: n = 512
Isolated CAE: n = 76
• Malignant tumors or other noncardiac conditions likely to cause death within 5 years
Mixture CAE: n = 436
Completed follow-up: n = 390
Fig. 2. Isolated diffuse ectasia in the right coronary artery (a). Isolated segmental ectasia in the left anterior descending artery (b). Discrete ectasia in the left anterior descending artery with coexisting stenosis (c). Segmental ectasia in the left circumflex artery with coexisting stenosis (d).
Prognosis in CAE
a
b
c
d
Cardiology 2015;131:251–259 DOI: 10.1159/000381702
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Fig. 1. Inclusion and exclusion criteria for this study.
Table 1. Clinical characteristics of the study patients
Risk factors Male Age, years BMI Hypertension Dyslipidemia Smoking Diabetes mellitus Family history of CAD Laboratory tests TC, mmol/l TG, mmol/l LDL-C, mmol/l HDL-C, mmol/l Hs-CRP, mg/l FBG, mmol/l
Total (n = 512)
Isolated CAE (n = 76)
Mixture CAE (n = 436)
p value
432 (84.4) 56.63 ± 11.39 21.93 ± 2.97 347 (67.8) 412 (80.5) 307 (60.0) 128 (25.0) 83 (16.2)
56 (74.0) 52.47 ± 12.39 21.50 ± 3.31 38 (50.0) 52 (68.4) 37 (48.7) 11 (14.5) 9 (11.8)
376 (86.2) 57.36 ± 11.06 22.00 ± 2.90 309 (70.9) 360 (82.6) 270 (61.9) 117 (26.8) 74 (17.0)
0.007 0.001 0.180 0.001 0.005 0.032 0.030 0.314
4.44 ± 1.20 1.65 (1.23 – 2.17) 2.63 ± 1.09 1.01 ± 0.28 1.92 (0.99 – 4.94) 5.64 ± 1.88
Clinical features Reasons for hospitalization AMI Angina Atypical symptoms Previous myocardial infarction Atrial fibrillation LVEF, % NYHA class I II III IV
4.35 ± 0.96 1.58 (1.18 – 2.04) 2.64 ± 1.13 1.11 ± 0.31 1.69 (0.88 – 3.14) 5.26 ± 1.38
4.45 ± 1.24 1.68 (1.25 – 2.20) 2.54 ± 0.88 1.00 ± 0.27 1.97 (0.99 – 5.35) 5.70 ± 1.95
0.483 0.226 0.432 0.005 0.126 0.018 2.0-censored
0.2
0
60
Follow-up (months)
1.0
0.4
20
d
Follow-up (months)
Event-free survival
Cumulative survival
Type I Type II Type III Type IV Type I-censored Type II-censored Type III-censored Type IV-censored
0.2
0
0 0
e
Markis class
0.6
20
40
60
80
Follow-up (months)
100
0
20
40
f
60
Follow-up (months)
Fig. 3. Cumulative survival curves (a, c, e) and event-free survival curves (b, d, f) of patients (comparison of iso-
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Zhang/Huang/Li/Guo/Zhu/Wang/Xu/ Gao/Li
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lated CAE and mixture CAE and Markis class and ectasia ratio groups).
There were several limitations of the current study. Firstly, the retrospective design and data from a single center were major limitations. Secondly, we were not able to complete follow-up data adequately. Finally, data collected over a relatively long term may have affected the quality of this study due to modifications in the technical procedure of PCI and improvements in the medical therapy for CAD. In the present follow-up study with a relatively large sample, we observed that the survival rate of patients with CAE appeared to be independent of coexisting CAD, the ectasia extent, and the ectasia severity.
Acknowledgments This work was partly funded by support from the National Natural Scientific Foundation (81070171 and 81241121), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20111106110013), the Capital Special Foundation of Clinical Application Research (Z121107001012015), the Capital Health Development Fund (2011400302), and the Beijing Natural Science Foundation (7131014) awarded to Dr. Jian-Jun Li, MD, PhD.
Conflict of Interest We declare that there are no conflicts of interests.
References
Prognosis in CAE
9 Valente S, Lazzeri C, Giglioli C, Sani F, Romano SM, Margheri M, Comeglio M, Gensini GF: Clinical expression of coronary artery ectasia. J Cardiovasc Med (Hagerstown) 2007;8: 815–820. 10 Bitigen A, Tanalp AC, Elonu OH, Karavelioglu Y, Ozdemir N: Mean platelet volume in patients with isolated coronary artery ectasia. J Thromb Thrombolysis 2007;24:99–103. 11 Zografos TA, Korovesis S, Giazitzoglou E, Kokladi M, Venetsanakos I, Paxinos G, Fragakis N, Katritsis DG: Clinical and angiographic characteristics of patients with coronary artery ectasia. Int J Cardiol 2013;167:1536–1541. 12 Sayin T, Doven O, Berkalp B, Akyurek O, Gulec S, Oral D: Exercise-induced myocardial ischemia in patients with coronary artery ectasia without obstructive coronary artery disease. Int J Cardiol 2001;78:143–149. 13 Demopoulos VP, Olympios CD, Fakiolas CN, Pissimissis EG, Economides NM, Adamopoulou E, Foussas SG, Cokkinos DV: The natural history of aneurysmal coronary artery disease. Heart 1997;78:136–141. 14 Sengul C, Cevik C, Ozveren O, Sunbul A, Kilicarslan F, Oduncu V, Can M, Semiz E, Dindar I: Assessment of atrial conduction time in patients with coronary artery ectasia. Pacing Clin Electrophysiol 2011;34:1468–1474. 15 Lee AY, Huang CL, Shyu MY: Ventricular fibrillation during coronary angiography in a patient with left dominant coronary artery ectasia. Exp Clin Cardiol 2012;17:79–80. 16 Ceyhan K, Koc F, Ozdemir K, Celik A, Altunkas F, Karayakali M, Kadi H, Ozturk A, Kaya MG: Coronary ectasia is associated with
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impaired left ventricular myocardial performance in patients without significant coronary artery stenosis. Med Princ Pract 2012;21: 139–144. Kosar F, Acikgoz N, Sahin I, Topal E, Aksoy Y, Cehreli S: Effect of ectasia size or the ectasia ratio on the thrombosis in myocardial infarction frame count in patients with isolated coronary artery ectasia. Heart Vessels 2005;20:199–202. Campeau L: Letter: Grading of angina pectoris. Circulation 1976;54:522–523. Hamm CW, Braunwald E: A classification of unstable angina revisited. Circulation 2000; 102:118–122. Markis JE, Joffe CD, Cohn PF, Feen DJ, Herman MV, Gorlin R: Clinical significance of coronary arterial ectasia. Am J Cardiol 1976; 37:217–222. Swanton RH, Thomas ML, Coltart DJ, Jenkins BS, Webb-Peploe MM, Williams BT: Coronary artery ectasia – a variant of occlusive coronary arteriosclerosis. Br Heart J 1978;40:393–400. Ismail AM, Rayan M, Adel A, Demerdash S, Atef M, Abdallah M, Nammas W: Prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia: study by 99m Tc-sestamibi radionuclide scintigraphy. Int J Cardiovasc Imaging 2014;30:425–430. Kosar F, Acikgoz N, Sahin I, Topal E, Gunen H, Ermis N, Cehreli S: Effects of co-existence of coronary stenosis and the extent of coronary ectasia on the TIMI frame count in patients with coronary artery ectasia. Int Heart J 2005;46:211–218.
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1 Swaye PS, Fisher LD, Litwin P, Vignola PA, Judkins MP, Kemp HG, Mudd JG, Gosselin AJ: Aneurysmal coronary artery disease. Circulation 1983;67:134–138. 2 Pinar Bermudez E, Lopez Palop R, Lozano Martinez-Luengas I, Cortes Sanchez R, Carrillo Saez P, Rodriguez Carreras R, Pico Aracil F, Valdes Chavarri M: Coronary ectasia: prevalence, and clinical and angiographic characteristics. Rev Esp Cardiol 2003;56:473–479. 3 Boles U, Zhao Y, David S, Eriksson P, Henein MY: Pure coronary ectasia differs from atherosclerosis: morphological and risk factors analysis. Int J Cardiol 2012;155:321–323. 4 Li JJ, He JG, Nan JL, He ZX, Zhu CG, Li J: Is systemic inflammation responsible for coronary artery ectasia? Int J Cardiol 2008; 130:e69–e70. 5 Brunetti ND, Salvemini G, Cuculo A, Ruggiero A, De Gennaro L, Gaglione A, Di Biase M: Coronary artery ectasia is related to coronary slow flow and inflammatory activation. Atherosclerosis 2014;233:636–640. 6 Gunes Y, Boztosun B, Yildiz A, Metin Esen A, Saglam M, Bulut M, Karapinar H, Kirma C: Clinical profile and outcome of coronary artery ectasia. Heart 2006;92:1159–1160. 7 Saglam M, Karakaya O, Barutcu I, Esen AM, Turkmen M, Kargin R, Esen O, Ozdemir N, Kaymaz C: Identifying cardiovascular risk factors in a patient population with coronary artery ectasia. Angiology 2007;58:698–703. 8 Aboeata AS, Sontineni SP, Alla VM, Esterbrooks DJ: Coronary artery ectasia: current concepts and interventions. Front Biosci (Elite Ed) 2012;4:300–310.
Cardiology 2015;131:251–259 DOI: 10.1159/000381702
Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia Yan Zhang a Qiao-Juan Huang a, b Xiao-Lin Li a Yuan-Lin Guo a Cheng-Gang Zhu a Xiao-Wei Wang c Bo Xu a Run-Lin Gao a Jian-Jun Li a
a
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, b Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, and c Kenli County Hospital, Shandong, China
Abstract Objectives: To assess the prognostic value of coexisting coronary artery disease (CAD), Markis class, and ectasia ratio for major adverse cardiovascular events in patients with coronary artery ectasia (CAE). Methods: A total of 512 consecutive patients with angiographically proven CAE were enrolled. Coronary ectasia extent was graded using the Markis class, and ectasia severity was assessed based on the ectasia ratio. Patients were followed up for a median of 34.6 months. Results: In the current study, 76 cases had isolated CAE, while the remaining 436 cases had coexisting CAD (mixture CAE). Males (84.4%) were predominantly affected, and the right coronary artery (55.1%) was most commonly involved. During follow-up, 86 overall major adverse cardiovascular events were diagnosed. Kaplan-Meier analysis failed to reveal any differences between isolated and mixture CAE in both cumulative and event-free survival analyses (p = 0.429 and p = 0.277, respectively). Moreover, when patients were divided into 4 groups according to Markis class (type I–IV) or
© 2015 S. Karger AG, Basel 0008–6312/15/1314–0251$39.50/0 E-Mail [email protected] www.karger.com/crd
2 groups based on the ectasia ratio (1.5–2.0 and >2.0), there was no significant difference in survival outcomes among the groups (p > 0.05). Conclusions: In this follow-up study with a relatively large sample, the survival rate of patients with CAE appeared to be independent of coexisting CAD and ectasia extent and severity. © 2015 S. Karger AG, Basel
Introduction
Coronary artery ectasia (CAE) has been defined as localized or diffuse dilation of coronary arteries exceeding 1.5-fold the diameter of the adjacent normal segment on coronary angiography [1]. CAE is a relatively rare abnormality of the coronary arterial tree and it is considered to be detected in 0.3–5.3% of consecutive angiographic series [2, 3]. The etiopathogenesis of CAE is completely unclear and more than half of the cases have been reported to be associated with coronary atherosclerosis. Furthermore, CAE has been reported to be linked to various con-
Y.Z. and Q.-J.H. contributed equally to this study.
Jian-Jun Li, MD, PhD, Division of Dyslipidemia State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences Peking Union Medical College, Beilishi Road 167, Beijing 100037 (China) E-Mail lijianjun938 @ 126.com
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Key Words Coronary artery ectasia · Coronary artery disease · Coronary angiography
Methods Study Population The study population was selected among 42,800 consecutive patients who underwent coronary angiography from May 2006 to August 2010 at our institution. As shown in figure 1, a total of 512 eligible consecutive patients with documented CAE were enrolled into the current study. For identification of patients with CAE, all patients with the terms ‘coronary ectasia’ or ‘coronary aneurysm’ in their catheterization reports were selected. Our study complied with the Declaration of Helsinki and was approved by the hospital ethics review board (Fu Wai Hospital and the National Center for Cardiovascular Diseases, Beijing, China). Information regarding traditional cardiovascular risk factors and symptoms as well as clinical findings was collected from medical records. In patients with typical symptoms, angina was assessed according to the Canadian Cardiovascular Society classifi-
252
Cardiology 2015;131:251–259 DOI: 10.1159/000381702
cation [18]. Hypertension was diagnosed according to repeated blood pressure measurements ≥140/90 mm Hg and/or consumption of antihypertensive drugs. Diabetes mellitus was diagnosed as fasting serum glucose levels ≥7.0 mmol/l in multiple determinations or if patients were being treated with insulin or oral hypoglycemic agents. Hyperlipidemia was considered to be present in patients with fasting total cholesterol ≥5.18 mmol/l or triglyceride ≥1.70 mmol/l. Current smoking was defined as having a history of cigarette smoking within the past year. CAD was defined as the presence of obstructive lesions >50% in at least 1 of the 3 major coronary arteries or major branches assessed by at least 2 independent senior interventional cardiologists. Unstable angina pectoris was defined as: new-onset angina within 2 months after a previous bout; angina with a progressive crescendo pattern, with the anginal episodes increasing in frequency and/or duration, and angina that occurred at rest [19]. Coronary Angiographic Evaluation A conventional coronary angiography was performed in all patients using Judkin’s technique. After obtaining images by standard approaches, each angiogram was interpreted by at least 2 independent cardiologists. The reference vessel was considered the most proximal part of the coronary artery that did not display any angiographic evidence of stenosis or abrupt ectasia. The maximum width of each ecstatic segment was measured in the view in which it appeared largest. The diagnosis of CAE was made according to standard criteria with a ratio of at least 1.5 [1]. Patients were considered to have isolated or mixture CAE according to the following criteria: isolated CAE (fig. 2a, b) was defined as no evidence of coronary stenosis, while mixture CAE (fig. 2c, d) was defined as angiographic evidence of CAD in addition to the dilated segment. Ectasia extent was evaluated and categorized according to Markis class [20]. Traditionally, the classification of Markis classes was as follows: (1) diffuse ectasia with ectatic lesions in two vessels (type I), (2) diffuse ectasia in one vessel and discrete ectasia in another (type II), (3) diffuse ectasia in one vessel (type III), and (4) discrete ectasia in one vessel (type IV). Ectasia severity was assessed based on the ectasia ratio (the diameter of the ectactic segment of the adjacent normal segment). According to the ectasia ratio, ectasias were divided into 2 groups: ectasias with a 1.5- to 2.0-fold increase and ecstasias with a more than 2.0-fold increase compared to the normal vessel diameter. The most frequent reasons for exclusion were: (1) patients with coronary stenosis that was so severe that the normal coronary reference diameter could not be determined, (2) patients with ectactic segments appearing within or directly associated with a coronary bypass graft, (3) patients with an ectactic segment in an area of previous percutaneous revascularization, (4) patients with CAE directly involving branching of coronary vessels, and (5) patients with valve (including mitral valve prolapse) or congenital heart disease or cardiomyopathy which may influence cardiac function evaluation. The design of this study and the complete inclusion/ exclusion criteria are displayed in figure 1. Follow-Up Follow-up data were obtained via standardized telephone interviews conducted by study nurses who were blinded to the aim of this study, after 24, 48, and 60 months. If patients reported that they had been hospitalized, appropriate hospital records were consulted. The primary endpoints were the composite of death, nonfatal acute myo-
Zhang/Huang/Li/Guo/Zhu/Wang/Xu/ Gao/Li
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ditions such as congenital abnormalities and inflammatory and connective tissue disorders [4–6]. The clinical significance of CAE remains poorly defined, and conflicting results have been reported. Due to its frequent coexistence with obstructive coronary artery disease (CAD), it has been considered to be a variant of coronary atherosclerotic disease [1, 7]. Several studies have found its clinical expression and long-term cardiac events to be mostly associated with the severity of stenotic coronary lesions, suggesting that isolated ectasia may be associated with a good prognosis at follow-up [1, 8, 9]. Nevertheless, multiple investigations have documented that CAE is not an innocent condition. Even in the absence of obstructive CAD, patients with CAE may still present with ischemia as well as acute coronary syndrome due to coronary spasm, a slow blood flow, platelet aggregation, thrombus formation, and so forth [10–15]. However, because of the low incidence of CAE in the general population, only a small number of patients can be enrolled into follow-up studies. Therefore, reliable data regarding long-term outcomes and evaluating the underlying impact factors of CAE are scarce. To date, the extent and severity of CAE are usually assessed based on the topographical extent of ectasia [16] (Markis class) and the ectasia ratio [17], respectively, which have been proved to be related to decreased thrombosis in myocardial infarction (TIMI) frame counts [11, 17]. However, the associations of the extent and severity of CAE with clinical outcomes have not been fully examined over a relatively long-term follow-up period. Thus, the aim of the present study was to evaluate the impact of 3 predictive fashions including coexisting CAD, Markis class, and ectasia ratio on the outcomes of CAE in a relatively large Chinese cohort.
Inclusion criteria: • Angiographically documented CAE • Men and women over 18 years of age • Written informed consent
Consecutive patients screened: n = 42,800
Exclusion criteria: • Coronary stenosis so severe that the normal coronary diameter could not be determined
Angiographically proven CAE: n = 556
• Ectactic segments within or associated with previous revascularization or directly involving the branch of coronary vessels • Valvular, congenital heart disease or cardiomyopathy
Eligible sample: n = 512
Isolated CAE: n = 76
• Malignant tumors or other noncardiac conditions likely to cause death within 5 years
Mixture CAE: n = 436
Completed follow-up: n = 390
Fig. 2. Isolated diffuse ectasia in the right coronary artery (a). Isolated segmental ectasia in the left anterior descending artery (b). Discrete ectasia in the left anterior descending artery with coexisting stenosis (c). Segmental ectasia in the left circumflex artery with coexisting stenosis (d).
Prognosis in CAE
a
b
c
d
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Fig. 1. Inclusion and exclusion criteria for this study.
Table 1. Clinical characteristics of the study patients
Risk factors Male Age, years BMI Hypertension Dyslipidemia Smoking Diabetes mellitus Family history of CAD Laboratory tests TC, mmol/l TG, mmol/l LDL-C, mmol/l HDL-C, mmol/l Hs-CRP, mg/l FBG, mmol/l
Total (n = 512)
Isolated CAE (n = 76)
Mixture CAE (n = 436)
p value
432 (84.4) 56.63 ± 11.39 21.93 ± 2.97 347 (67.8) 412 (80.5) 307 (60.0) 128 (25.0) 83 (16.2)
56 (74.0) 52.47 ± 12.39 21.50 ± 3.31 38 (50.0) 52 (68.4) 37 (48.7) 11 (14.5) 9 (11.8)
376 (86.2) 57.36 ± 11.06 22.00 ± 2.90 309 (70.9) 360 (82.6) 270 (61.9) 117 (26.8) 74 (17.0)
0.007 0.001 0.180 0.001 0.005 0.032 0.030 0.314
4.44 ± 1.20 1.65 (1.23 – 2.17) 2.63 ± 1.09 1.01 ± 0.28 1.92 (0.99 – 4.94) 5.64 ± 1.88
Clinical features Reasons for hospitalization AMI Angina Atypical symptoms Previous myocardial infarction Atrial fibrillation LVEF, % NYHA class I II III IV
4.35 ± 0.96 1.58 (1.18 – 2.04) 2.64 ± 1.13 1.11 ± 0.31 1.69 (0.88 – 3.14) 5.26 ± 1.38
4.45 ± 1.24 1.68 (1.25 – 2.20) 2.54 ± 0.88 1.00 ± 0.27 1.97 (0.99 – 5.35) 5.70 ± 1.95
0.483 0.226 0.432 0.005 0.126 0.018 2.0-censored
0.2
0
60
Follow-up (months)
1.0
0.4
20
d
Follow-up (months)
Event-free survival
Cumulative survival
Type I Type II Type III Type IV Type I-censored Type II-censored Type III-censored Type IV-censored
0.2
0
0 0
e
Markis class
0.6
20
40
60
80
Follow-up (months)
100
0
20
40
f
60
Follow-up (months)
Fig. 3. Cumulative survival curves (a, c, e) and event-free survival curves (b, d, f) of patients (comparison of iso-
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lated CAE and mixture CAE and Markis class and ectasia ratio groups).
There were several limitations of the current study. Firstly, the retrospective design and data from a single center were major limitations. Secondly, we were not able to complete follow-up data adequately. Finally, data collected over a relatively long term may have affected the quality of this study due to modifications in the technical procedure of PCI and improvements in the medical therapy for CAD. In the present follow-up study with a relatively large sample, we observed that the survival rate of patients with CAE appeared to be independent of coexisting CAD, the ectasia extent, and the ectasia severity.
Acknowledgments This work was partly funded by support from the National Natural Scientific Foundation (81070171 and 81241121), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20111106110013), the Capital Special Foundation of Clinical Application Research (Z121107001012015), the Capital Health Development Fund (2011400302), and the Beijing Natural Science Foundation (7131014) awarded to Dr. Jian-Jun Li, MD, PhD.
Conflict of Interest We declare that there are no conflicts of interests.
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