Impact of the Presence of Chronic Total Occlusion in a Non-Infarct-Related Coronary Artery in Acute Myocardial Infarction Patients

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1 Impact of the Presence of Chronic Total Occlusion in a Non-Infarct-Related Coronary Artery in Acute Myocardial Infarction Patients Validation in a Subset of Patients With Preserved Left Ventricular Function After Successful Primary Percutaneous Coronary Intervention Yukio Mizuguchi, 1 MD, Akihiko Takahashi, 1 MD, Sho Hashimoto, 1 MD, Takeshi Yamada, 1 MD, Norimasa Taniguchi, 1 MD, Shunsuke Nakajima, 1 MD, and Tetsuya Hata, 1 MD Summary Chronic total occlusion (CTO) in a non-infarcted-related artery was reported to worsen immediate clinical outcome in acute myocardial infarction (AMI) patients. However, the prognosis of such patients with preserved left ventricular function after successful primary percutaneous coronary intervention (PCI) has not yet been clarified. The aim of the present study was to evaluate whether the presence of CTO contributes to a worse prognosis even in patients with preserved left ventricular function after primary PCI. We retrospectively analyzed 353 consecutive patients with acute myocardial infarction, whose left ventricular ejection fraction (LVEF) was not less than 40% in the echocardiography performed 1 day after primary PCI. We divided the patients into two groups according to the presence (n = 25) or absence (n = 328) of CTO in the non-infarct-related coronary artery, and compared the clinical outcome of patients between the two groups. The LVEF estimated by echocardiography after primary PCI was similar between patients with and without CTO (55.1 ± 8.6% versus 58.0 ± 9.4%; P = 0.07). The peak creatine kinase value was also similar between the two groups (1539 versus 1921 U/L; P = 0.33); however, CTO patients were significantly more likely to undergo intra-aortic balloon pumping (56.0% versus 12.5%; P < 0.001) during primary PCI, and 30-day mortality was significantly higher in CTO patients (12.0% versus 0.9%; P < 0.001). By multivariate analysis, cardiogenic shock at arrival was significantly correlated with 30-day mortality. Even though the LVEF of AMI patients with CTO was preserved after successful PCI, a high mortality rate was observed. (Int Heart J 2015; 56: ) Key words: Chronic total coronary occlusion, Cardiogenic shock Coronary chronic total occlusion (CTO) is commonly found on approximately 15-30% of all diagnostic coronary angiographies (CAGs), in patients with significant coronary artery disease. 1,2) Although the treatment of CTO remains a technical challenge and still 20-35% of CTOs are not recanalized by percutaneous coronary intervention (PCI) even when performed by experienced operators, 3,4) successful PCI for CTO has been shown to improve left ventricular (LV) systolic function, reduce angina, increase exercise capacity, and reduce the need for late bypass surgery. 3,5,6) On the other hand, CTO patients who were not revascularized had a significantly higher rate of cardiac mortality and sudden cardiac death compared with those who were revascularized. 7,8) Moreover, in acute myocardial infarction (AMI) patients, the presence of CTO in a non-infarct-related artery (IRA) is a strong and independent risk factor for short- and middle-term mortality. 9-11) However, it is unclear whether the subset of patients with CTO who present well preserved LV function after primary PCI would show the same results. The aim of this retrospective study was to evaluate the impact of the presence of CTO on the prognosis in the subset of CTO patients complicated with AMI and presenting wellpreserved LV function after primary PCI. Methods Study population: Between January 2008 and December 2012, 473 patients with first-onset AMI underwent primary PCI within 24 hours from symptom onset in our hospital. Patients complicated with cardiopulmonary arrest outside the hospital (n = 33), a left main trunk culprit lesion (n = 23), re- From the 1 Department of Cardiovascular, Sakurakai Takahashi Hospital, Kobe, Japan. Address for correspondence: Yukio Mizuguchi, MD, Department of Cardiovascular, Sakurakai Takahashi Hospital, Oikecho, Suma-ku, Kobe, Hyogo , Japan. yukiomizuguchi@gmail.com Received for publication February 16, Revised and accepted May 11, Released in advance online on J-STAGE November 6, All rights reserved by the International Heart Journal Association. 592

2 Vol 56 No 6 CHRONIC TOTAL OCCLUSION 593 quiring extracorporeal membrane oxygenator (n = 12), and patients presenting with poor left ventricular function (LVEF < 40%) after successful PCI (n = 52) were excluded. The remaining 353 patients were divided into two groups; patients with CTO (n = 25) and those without CTO (n = 328), and clinical indices including patient demographics, clinical and angiographic characteristics, and in-hospital and 30-day outcomes were compared. Cardiogenic shock on admission was defined according to the following clinical criterion used in the SHOCK trial: 5) hypotension defined as systolic blood pressure < 90 mmhg for at least 30 minutes or the need for supportive measures to maintain systolic blood pressure 90 mmhg, and end-organ hypoperfusion defined as cold extremities or a urine output of < 30 ml/hour and a heart rate 60 beat/minute. In-hospital management: Coronary angiography and subsequent PCI were performed immediately after the diagnosis of AMI. CTO was considered to be total occlusion of the artery lumen without anterograde flow or with flow (anterograde or retrograde) through collateral vessels in an artery other than the culprit artery. The differentiation between CTO and acute occlusion was likewise based on the morphologic analysis (absence of fresh thrombus and presence of well-developed collateral circulation or microchannels) by the interventional cardiologist who performed the procedure. The door-to-balloon time was defined as the period of time elapsed between patient arrival at our hospital and the beginning of the mechanical reperfusion procedure. The door time is characterized by the patients arrival at our hospital, signaled by the moment they took a number to be evaluated (before the patient is checked-in in that hospital area), which is automatically recorded by the information system. The balloon time refers to the beginning of the reperfusion procedure, defined by the percutaneous insertion of any device with therapeutic purposes. Usually, this first device is the aspiration thrombectomy device or angioplasty balloon catheter. The use of intra-aortic balloon pumping during PCI was determined by the operator s discretion, mainly according to the dominance of the CTO-related myocardial territory or severity of hemodynamic compromise before and during PCI. After the intervention, all patients were admitted to a coronary care unit. The patients underwent transthoracic echocardiography on day 1 after PCI, and LV ejection fraction was assessed by the biplane method of discs (ie, according to the modified Simpson s rule). Left ventricular volume was measured from the apical 4-chamber and 2-chamber views. Serum creatine kinase isozyme level was measured at baseline and 3, 6, 9, 12, and 24 hours after PCI. Major adverse cardiac events (MACE) were defined as death, myocardial infarction, or target vessel revascularization during 1-year follow-up. Statistical analysis: All data were analyzed retrospectively. Categorical variables are expressed as numbers and percentages, and continuous variables as the mean ± standard deviation. After testing for normal distribution, differences were compared using the unpaired Student s t-test, the χ 2 test, or Fisher s exact test where appropriate. Univariate and multivariate logistic regression analyses were performed to correlate 30-day mortality with several clinical variables. All statistical analyses were performed with StatMate version 5 (ATMS Co., Ltd., Tokyo). A two-tailed P-value < 0.05 was considered statistically significant. Figure. Patient flow chart. AMI indicates acute myocardial infarction; PCI, percutaneous intervention; LVEF, left ventricular ejection fraction; ECMO, extracorporeal membrane oxygenator; and CTO, chronic total occlusion. Results Among the 353 patients undergoing emergency PCI for AMI and whose LVEF was 40%, 25 (7.1%) had CTO lesions in a non-infarct-related artery (referred to as the CTO group hereafter) (Figure). There were 250 patients with ST-segment elevated myocardial infarction and 103 patients with non-stsegment elevated myocardial infarction among the 353 patients. The CTO lesion was located in the right coronary artery, left circumflex artery, and left anterior descending artery in 7, 6, and 11 cases, respectively. The LVEF estimated by echocardiography after primary PCI was similar between the CTO group and patients without CTO lesion (referred to as the non-cto group hereafter) (55.1 ± 8.6% versus 58.0 ± 9.4%; P = 0.15). The incidence of cardiogenic shock (24.0% versus 7.6%; P < 0.05) and the use of intra-aortic balloon pumping (IABP) (56.0% versus 12.5%; P < 0.001) for hemodynamic support during PCI were higher in the CTO group than in the non-cto group. Door-to-balloon (first device used) time was also significantly longer in the CTO group than in the non-cto group (96.6 versus 55.2 minutes; P < 0.01). However, the peak creatinine kinase levels were similar between the groups (1539 versus 1921 U/L; P = 0.33). High Thrombolysis in Myocardial Infarction grade 3 coronary flow after PCI was observed in both groups. Regarding the puncture site of PCI, there were no significant differences between the CTO and non-cto groups. Blood transfusion was performed more frequently in the CTO group than in the non-cto group (36.0% versus 10.2%; P < 0.001). The inhospital and 30-day mortality rates in the CTO group were significantly higher than those in the non-cto group (12.0% versus 1.5%; P < and 12.0% versus 0.9%; P < 0.001, respectively) (Table I). The cause of death in the non-cto patients was ventricular septal perforation in one patient and pneumonia and multiple organ dysfunction syndrome (MODS) in 4 patients. The cause of death in the CTO patients was septic shock, pneumonia, acute respiratory distress syndrome

3 594 MIZUGUCHI, ET AL Int Heart J November 2015 Table I. Baseline Clinical Characteristics, Procedures, and Complications According to the Presence of Chronic Total Occlusion in the Non-Culprit Artery in Patients With Preserved Cardiac Output CTO group LVEF > 40% (n = 25) non-cto group LVEF > 40% (n = 328) Age (years) 71.2 ± ± 12.8 NS Sex (men/women), n 18 / / 101 NS Cardiovascular risk factors, n (%) Hypertension 20 (80.0) 194 (59.1) NS Diabetes mellitus 6 (24.0) 110 (33.5) NS Dyslipidemia 11 (44.0) 122 (37.2) NS Current smoker 11 (44.0) 133 (40.6) NS Peak CK (U/L) 1539 ± ± 1898 NS CCr (ml/minute) 72.3 ± ± 40.2 NS Ejection fraction (day 1 post-pci) (%) 55.1 ± ± 9.4 NS Culprit lesion, n (%) LAD 11 (44.0) 135 (40.8) NS LCX 7 (28.0) 57 (17.2) NS RCA 8 (32.0) 139 (42.0) NS Number of stenosed vessels, n (%) (51.2) < (48.0) 107 (32.6) NS 3 13 (52.0) 53 (16.2) < Site of CTO lesion LAD 9 (36.0) LCX 7 (28.0) RCA 10 (40.0) PCI approach site, n (%) Radial artery 22 (88.0) 309 (94.2) NS Brachial artery 1 (4.0) 7 (2.1) NS Femoral artery 2 (8.0) 12 (3.7) NS Door-to-balloon (first device used) time, (minutes) 96.6 ± ± 41.0 < 0.01 IABP, n (%) 14 (56.0) 41 (12.5) < ECMO, n (%) 0 (0) 0 (0) NS Final TIMI grade flow < 3, n (%) 0 (0) 2 (0.6) NS Blood transfusion, n (%) 9 (36.0) 33 (10.2) < Minimum hemoglobin level (mg/dl), n (%) 9.6 ± ± 1.9 < 0.05 Cardiogenic shock, n (%) 6 (24.0) 25 (7.6) < day mortality, n (%) 3 (12.0) 3 (0.9) < In-hospital mortality, n (%) 3 (12.0) 5 (1.5) NS PCI to CTO lesions in the first hospitalization, n (%) 15 (60.0) Follow-up angiography or CT angiography, n (%) 12 (48.0) 224 (68.3) < 0.05 MACE (1-year follow-up), n (%) 10 (40.0) 61 (18.6) < 0.05 Death 5 (20.0) 10 (3.1) < Re-infarction 2 (8.0) 3 (0.9) < 0.05 CTO indicates chronic total occlusion in the non-culprit artery; MACCE, major adverse cardiac and cerebrovascular event; LVEF, left ventricular ejection fraction; CCr, creatinine clearance; CK, creatinine kinase; PCI, percutaneous coronary intervention; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; IABP, intraaortic balloon pumping; ECMO, extracorporeal membrane oxygenation; TIMI, thrombolysis in myocardial infarction; and TVR, target vessel revascularization. The data are presented as number (%) or mean ± standard deviation. P (ARDS), and MODS. By univariate analysis, cardiogenic shock at arrival and CTO were associated with 30-day mortality (odds ratio [OR] 37.02, 95% confidence interval [CI] , P < and OR 20.42, 95% CI , P < 0.001, respectively). By multivariate analysis, cardiogenic shock at arrival was significantly correlated with 30-day mortality (odds ratio [OR] 22.82, 95% CI , P < 0.05) (Table II). In this study, the patients who had the RCA-CTO lesion combined with LCX-AMI lesion were more likely to be in cardiogenic shock. However, there were no significant relationships between cardiogenic shock, mortality, and the location of the CTO lesion, IRA (Table III). Discussion In the present study, we demonstrated that the presence of CTO in a non-infarct-related coronary artery contributed to the higher incidence of cardiogenic shock at the time of admission and subsequent poor prognosis in the patient subset with preserved LV function after primary PCI. In fact, the 30-day mortality rate was almost 13 times as high as that of patients without CTO. The study results also illustrated that patients with CTO presented longer door-to-balloon time and were more likely to undergo IABP during PCI and receive a blood transfusion. Several recent observational studies including our previous report suggested that the coexistence of CTO lesions in the

4 Vol 56 No 6 CHRONIC TOTAL OCCLUSION 595 Table II. Analysis of the Relationship Between the AMI Patients With Preserved Cardiac Output and 30-day Mortality Univariate analysis Multivariate analysis Odds ratio (95% CI) P Odds ratio (95% CI) P Cardiogenic shock ( ) < ( ) < 0.05 CTO ( ) < ( ) 0.07 Age 1.10 ( ) < ( ) 0.18 Male sex 1.75 ( ) NS Cardiovascular risk factors Hypertension 2.51 ( ) NS Diabetes mellitus 3.05 ( ) NS Dyslipidemia 1.09 ( ) NS Current and past smoker ( ) NS Smoking index 1.00 ( ) NS Previous MI 2.44 ( ) NS Previous PCI or CABG 5.44 ( ) NS Previous CI 2.93 ( ) NS Peak CK 0.99 ( ) NS Door-to-reperfusion time 1.00 ( ) NS Ccr 0.97 ( ) < ( ) 0.99 Culprit lesion LAD 0.37 ( ) NS LCX 3.01 ( ) NS RCA 0.95 ( ) NS Site of CTO lesion LAD 0.88 ( ) NS LCX 0 NS RCA 3.50 ( ) NS MVD 3.41 ( ) NS MVD without CTO 0.32 ( ) NS Blood transfusion ( ) < ( ) 0.19 AMI indicates acute myocardial infarction; 95% CI, 95% confidence interval; CTO, chronic total occlusion in nonculprit artery; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; CI, cerebral infarction; CK, creatinine kinase; CCr, creatinine clearance; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; and MVD, multivessel disease. Table III. Relationship Between IRA, CTO Lesion and Cardiogenic Shock, Mortality Location of CTO lesion/ Infarct related artery LAD LCX RCA LAD & LCX P RCA LCX LAD RCA LAD LCX LAD & LCX RCA Number NS Shock NS Deaths at 30 days NS IRA indicates infarct related artery; CTO, chronic total occlusion in the non-culprit artery; LAD, left anterior descending artery; LCX, left circumflex artery; and RCA, right coronary artery. non-ira worsens the clinical outcomes of AMI, 9,10,12-14) but none of these studies examined stratified analysis of the patient subsets according to the LV function after primary PCI. In this regard, this is the first study to evaluate the prognosis of patients with preserved LV function after AMI. Cardiogenic shock at arrival was significantly correlated with 30-day mortality by multivariate analysis. Generally, the occurrence of cardiogenic shock after AMI depends on the myocardial territory at risk; therefore, patients with CTO in a non-culprit lesion are considered to be more prone to cardiogenic shock as compared with patients without CTO, and it depends upon the degree of collateral blood supply from the coronary vessel with the culprit lesion. Furthermore, those patients tend to require further clinical evaluation and adjunctive procedures such as IABP insertion or ventilation for acute respiratory failure, and these procedures before PCI may affect the door-to-balloon time and incidence of blood transfusion, which may contribute to a poor clinical outcome. The main causes of death in CTO patients in the current study were pneumonia, septic shock, ARDS, and MODS. In our cases, ARDS was considered to be induced by the temporary cardiogenic shock which occurred before and during primary PCI, as its correlation to ARDS is well established. 15,16) Furthermore, sustained malperfusion due to untreated CTO also may affect the recovery process from cardiogenic shock and lead to a worse outcome as compared to patients without cardiogenic shock. A similar result was reported by Bataille, et al 17) in which they found no patient with CTO presenting with cardiogenic shock survived beyond 30 days in their study population even after successful coronary recanalization. It was reported that the AMI rate of patients with stable angina pectoris after PCI was 0.5% at 1 year, 1.1% at 3 years, and 3.0% at 5 years in a Japanese population. 18) Chen, et al 19) reported that PCI to non-ira in AMI patients with multivessel

5 596 MIZUGUCHI, ET AL Int Heart J November 2015 disease was superior to conservative treatment in improving the clinical outcomes of their patients. The results of the current study may justify an elective PCI procedure for patients with a CTO lesion even in the absence of ischemia. This is also supported by a recent study reporting that the incidence of sudden death was 5 times greater in patients with CTO who were not revascularized than in those who were revascularized. 7) Study limitations: The foremost limitation of this study is its non-randomized retrospective observational design, which implies the absence of both a data safety monitoring board and blinded core laboratory. Second, we defined the preserved LV heart function as LVEF over 40% by ultrasound cardiogram validation regardless of the use of catecholamine, IABP, or ventilator; therefore, we may have overestimated the cardiac function in some patients. Third, this study was carried out with a small sample size and short follow-up period. Conclusions: In AMI patients with CTO, even if their LVEF was preserved after successful primary PCI, the short-term prognosis is poor as compared to that of AMI patients without CTO. The cause of such poor prognosis was strongly associated with initial cardiogenic shock at the time of arrival to the hospital. Conflict of interest: None Disclosure References 1. Fefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol 2012; 59: Kahn JK. Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting. Am Heart J 1993; 126: Suero JA, Marso SP, Jones PG, et al. Procedural outcomes and long-term survival among patients undergoing percutaneous coronary intervention of a chronic total occlusion in native coronary arteries: a 20-year experience. J Am Coll Cardiol 2001; 38: Mehran R, Claessen BE, Godino C, et al. Long-term outcome of percutaneous coronary intervention for chronic total occlusions. JACC Cardiovasc Interv 2011; 4: Melchior JP, Doriot PA, Chatelain P, et al. Improvement of left ventricular contraction and relaxation synchronism after recanalization of chronic total coronary occlusion by angioplasty. J Am Coll Cardiol 1987; 9: Olivari Z, Rubartelli P, Piscione F, et al. Immediate results and one-year clinical outcome after percutaneous coronary interventions in chronic total occlusions: data from a multicenter, prospective, observational study (TOAST-GISE). J Am Coll Cardiol 2003; 41: Godino C, Bassanelli G, Economou FI, et al. Predictors of cardiac death in patients with coronary chronic total occlusion not revascularized by PCI. Int J Cardiol 2013; 168: Arslan U, Balcioglu AS, Timurkaynak T, Cengel A. The clinical outcomes of percutaneous coronary intervention in chronic total coronary occlusion. Int Heart J 2006; 47: Gierlotka M, Tajstra M, Gąsior M, et al. Impact of chronic total occlusion artery on 12-month mortality in patients with non-stsegment elevation myocardial infarction treated by percutaneous coronary intervention (from the PL-ACS Registry). Int J Cardiol 2013; 168: Mozid AM, Mohdnazri S, Mannakkara NN, et al. Impact of a chronic total occlusion in a non-infarct related artery on clinical outcomes following primary percutaneous intervention in acute ST-elevation myocardial infarction. J Invasive Cardiol 2014; 26: Tajstra M, Gasior M, Gierlotka M, et al. Comparison of five-year outcomes of patients with and without chronic total occlusion of noninfarct coronary artery after primary coronary intervention for ST-segment elevation acute myocardial infarction. Am J Cardiol 2012; 109: Yang ZK, Zhang RY, Hu J, Zhang Q, Ding FH, Shen WF. Impact of successful staged revascularization of a chronic total occlusion in the non-infarct-related artery on long-term outcome in patients with acute ST-segment elevation myocardial infarction. Int J Cardiol 2013; 165: Ariza-Solé A, Teruel L, di Marco A, et al. Prognostic impact of chronic total occlusion in a nonculprit artery in patients with acute myocardial infarction undergoing primary angioplasty. Rev Esp Cardiol 2014; 67: Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med 1999; 341: Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149: (Review) 16. Garber BG, Hébert PC, Yelle JD, Hodder RV, McGowan J. Adult respiratory distress syndrome: a systemic overview of incidence and risk factors. Crit Care Med 1996; 24: Bataille Y, Déry JP, Larose É, et al. Deadly association of cardiogenic shock and chronic total occlusion in acute ST-elevation myocardial infarction. Am Heart J 2012; 164: Kaneko H, Yajima J, Oikawa Y, et al. Recent characteristics and outcomes of Japanese stable angina pectoris after percutaneous coronary intervention. An observational cohort study using the Shinken Database. Int Heart J 2013; 54: Chen HC, Tsai TH, Fang HY, et al. Benefit of revascularization in non-infarct-related artery in multivessel disease patients with STsegment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Int Heart J 2010; 51: