RCA Disease and Unprotected LM Stenting

Transcription

1 Original Article RCA Disease and Unprotected LM Stenting Acta Cardiol Sin 2011;27:14 20 Coronary Heart Disease The Clinical Significance of Right Coronary Artery Stenosis on the Prognosis of Patients with Unprotected Left Main Disease Undergoing Percutaneous Coronary Intervention Tse-Min Lu, 1 Yu-Lan Jou, 2 Ying-Hwa Chen, 1 Lung-Ching Chen, 1 Shih-Hsien Sung, 1 Wan-Leong Chan 1 and Shing-Jong Lin 1 Background: Although coronary artery bypass grafting remains the standard treatment for unprotected left main (LM) coronary artery disease, percutaneous coronary intervention (PCI) with the use of stent has become an alternative treatment. In this study, we aimed to evaluate the real-world results of patients with LM disease treated with PCI and compare the impact of significant right coronary artery (RCA) disease on the short-term and long-term outcomes of these patients. Methods and Results: A total of 164 patients were included, with 95 patients (57.9%) with significant RCA stenosis and 69 (42.1%) patients without, and were followed up over a mean period of 2.5 years. EuroSCORE 6 was noted in 78 patients (47.6%). Within the 30-day period after index procedure, major adverse cardiovascular events (MACE) were observed in 16 (9.9%) patients, including 15 (9.3%) deaths, and 1 non-fatal myocardial infarction (0.6%). Three patients suffered from probable sub-acute stent thrombosis (1.8%). In the stepwise multivariate Cox regression analysis, female gender, left ventricular ejection fraction < 40% and RCA disease were identified as the significant independent predictors of 30-day deaths and MACE. As for the long-term outcomes, the mean follow-up period was 2.5 years (range 1 month to 9.7 years, median 23.4 months). There were 38 deaths (23.6%), and 57 MACE (35.4%). The survival of LM patients with RCA disease remained worse than that of those without (p < 0.01), and concomitant RCA disease remained significant prognostic predictor after being adjusted by other variables. Conclusion: In this real-world practice in a single center, we found that unprotected LM stenting in patients with concomitant significant stenosis of RCA may be associated with worse early and long-term outcomes compared with those without RCA disease. Key Words: Left main stenting Percutaneous coronary intervention Right coronary artery BACKGROUND Received: March 30, 2010 Accepted: July 27, Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming University; 2 Division of Internal Medicine, Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan. Address correspondence and reprint requests to: Dr. Tse-Min Lu, Division of Cardiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. Tel: ; Fax: ; tmlu@vghtpe.gov.tw Although coronary artery bypass grafting (CABG) remains the standard treatment for unprotected left main (LM) coronary artery disease, percutaneous coronary intervention (PCI) with the use of stent, especially the drug-eluting stent (DES), has become an alternative treatment to CABG in these patients with LM disease, with similar outcomes when compared with CABG, 1-11 and was supported by current American College of Car- Acta Cardiol Sin 2011;27:

2 RCA Disease and Unprotected LM Stenting diology/american Heart Association (ACC/AHA) guidelines for PCI with the recommendation level of class IIb. 12 However, the choice of treatment sometimes may be difficult, especially in the presence of significant stenosis of the right coronary artery (RCA), which may increase the peri-procedural risk of LM PCI, and may have a substantial impact on the long-term prognosis of these patients due to incomplete revascularization. To the best of our knowledge, few studies have addressed this issue. Therefore, in this study, we aimed to evaluate the real world results of patients with LM disease treated with PCI, including patients with wide-range of risk profile, from elective procedure to acute coronary syndrome and/or cardiogenic shock, and to determine the potential impact of significant RCA disease on the short-term and long-term clinical outcome of unprotected LM patients undergoing PCI. METHODS This study included 164 consecutive patients with unprotected LM disease undergoing PCI in Taipei Veterans General Hospital from January 2000 to December Acute ST segment elevation myocardial infarction with totally occluded LM as the only culprit lesion was the only exclusion criteria. Left main disease was considered unprotected if there were no patent coronary artery bypass grafts to the left anterior descending or left circumflex arteries. Significant RCA disease was defined as lumen narrowing greater than 50% of the main vessel of the RCA. PCI was performed with standard procedure, with all patients having given informed consent for the procedures. Unfractionated heparin (10,000 IU bolus) was administered before the procedure to achieve an activated clotting time > 300 sec. Predilatation with balloon catheter was performed in all cases. For most LM cases with distal bifurcation involved, stenting across the bifurcation toward the left anterior descending artery (cross-over technique) was attempted, followed by provisional stenting of the left circumflex artery (Tstenting or culottes stenting) if there was residual significant stenosis or dissection over the orifice of the left circumflex artery. Mini-crush stenting and V-stenting techniques were used in 5 and 3 cases, respectively, by the preference of the interventional operator and suitable LM anatomy. Post-dilation with kissing balloon technique was attempted in all cases except technique difficulty or small indominant left circumflex artery. The deployment of stent was performed by high-pressure balloon dilatation to achieve optimal stent apposition. Debulking by means of rotablator was used only in highly calcified lesions, and the use of intravascular ultrasound (IVUS) and glycoprotein IIb/IIIa receptor antagonist were at the discretion of the interventional operator. Intra-aortic balloon pump (IABP) was applied in patients with complex lesions and depressed left ventricular function, as well as in hemodynamic unstable patients. PCI was considered angiographically successful if residual stenosis < 30% with coronary Thrombolysis in Myocardial Infarction grade 3 flow was obtained at the end of the procedure. After the procedure, all patients received aspirin (100 mg/d) indefinitely and clopidogrel (300 mg loading dose, then 75 mg per day) or ticlopidine (500 mg loading dose, then 250 mg twice a day) for at least 1 month (bare metal stent, BMS) or 6 months (DES). Medications for treatment of angina pectoris (calcium channel blockers, beta-blockers and nitrates) were continued. The additive and logistic EuroSCORE were used to stratify the risk of total mortality and MACE at followup, and were calculated based on the original methodology 13 by 2 experienced cardiologists unaware of the clinical course of patients. Patients were considered high-risk in the presence of additive EuroSCORE 6. The clinical follow-up data was collected by scheduled monthly clinic evaluations or direct telephone contact for the first-ever major adverse cardiovascular events (MACE), which were defined as all-cause mortality, non-fatal myocardial infarction (MI) and clinically driven target lesion revascularization (TLR). Myocardial infarction was defined as creatine phosphokinase elevation 3 times the upper limit of normal after the index procedure. Target lesion revascularization (TLR) was defined as any repeated percutaneous intervention of the target lesion performed for > 50% angiographic re-narrowing of the treated lesion from 5 mm proximal to the stent and 5 mm distal to the stent. Stent thrombosis occurrence was classified as definite, probable, or possible according to Academic Research Consortium (ARC) criteria, 14 and was considered as acute within 24 hours from the procedure, subacute if occurred within 30 days 15 Acta Cardiol Sin 2011;27:14 20

3 Tse-MinLuetal. after the procedure, late and very late when it occurred after 30 days within 12 months and after 1 year, respectively. Statistical analysis All continuous variables were presented as mean standard deviation, and categorical variables as numbers and percentages. All patients were divided into 2 groups according to the presence of absence of RCA disease. Between patients with and without significant RCA disease, continuous variables were compared with Student s t-test or Mann Whitney test whenever appropriate, and categorical data was compared by means of Chi-square test or Fisher exact test. Actuarial event-free survival curves were estimated by use of the Kaplan-Meier method and compared by log-rank test. Univariate and stepwise multivariate Cox proportional hazards regression analysis was performed to determine the independent predictors of long-term total mortality and MACE for all patients studied. All the variables presented in Table 1 were tested and those with a p < 0.1 were included into this multivariate model. The relative risk (RR) and 95% confidence intervals were calculated. A p value of less than 0.05 was considered to be statistically significant. The SPSS 17.0 (SPSS Inc., Chicago, Illinois, US) software package was used for statistical analysis. RESULTS Patient characteristics A total of 164 patients were included in the study, with 95 patients (57.9%) with significant RCA stenosis and 69 (42.1%) patients without. The baseline characteristics are summarized in Table 1. In patients with RCA disease, most had more than 70% stenosis over the RCA lesions (80/95, 84%, with 9 chronic total occlusion of RCA). More than half of patients presented as non STelevation (NSTE) acute coronary syndrome (88 patients, 55%, with unstable angina in 32 patients, 20%; and NSTE-MI in 56 patients, 35%). In addition, there were 15 (9.3%) patients presenting as cardiogenic shock. In particular, 75 patients (47%) and 48 patients (30%) suffered from diabetes and chronic renal failure, respectively. EuroSCORE 6 was noted in 78 patients (47.6%). All of these features suggested that these study patients belonged actually to a high-risk population. Compared to patients without RCA disease, the patients with significant RCA stenosis were more likely to have old MI, chronic renal failure, and more likely to have presented as MI. In addition, there was a trend for patients with RCA stenosis to be accompanied with cardiogenic shock (p = 0.069). Procedural characteristics PCI procedures were successful in all patients except two cases (98.8%), who underwent emergent CABG immediately after PCI. Distal bifurcation of the LM was much more often involved than ostial/mid-shaft of the LM (122 versus 42 patients, 74.4% versus 25.6%). In addition, patients with LM disease much more often had three-vessels involved (76 patients, 46.3%), compared to the involvement of one vessel (29 patients, 17.7%), two vessels (42 patients, 25.6%) or only the LM being involved (17 patients, 10.4%). Drug-eluting stents were Table 1. Baseline characteristics RCA(-) n = 69 RCA(+) n = 95 p value Age (yrs) Gender/male (n) 58 (84.1%) 83 (87.4%) DM 28 (40.6%) 48 (50.5%) Hypertension 50 (72.5%) 73 (76.8%) Hypercholesterolemia 37 (53.6%) 52 (54.7%) Smoking 07 (10.1%) 8 (8.4%) BMI(kg/m 2 ) COPD 3 (4.3%) 7 (7.4%) PAOD 09 (13.0%) 8 (8.4%) Previous MI 14 (20.3%) 40 (42.1%) Old CVA 09 (13.0%) 13 (13.7%) CRF 14 (20.3%) 34 (35.8%) LVEF (%) Clinical presentation Stable angina 34 (49.3%) 40 (41.1%) Unstable angina 18 (26.1%) 16 (16.8%) MI 17 (24.6%) 39 (41.1%) Cardiogenic shock 3 (4.3%) 12 (12.6%) EuroSCORE, additive EuroSCORE, logistic EuroSCORE 6 40 (58.0%) 59 (62.1%) BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRF, chronic renal failure; CVA, cerebrovascular accident; DM, diabetes mellitus; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PAOD, peripheral arterial occlusive disease. Acta Cardiol Sin 2011;27:

4 RCA Disease and Unprotected LM Stenting used in 78 patients (47.6%), with total stent length longer in patients with RCA disease. The majority of patients with distal bifurcation involvement were treated with a single stent with cross-over technique (n = 98, 60%). In patients treated with more than one stent, T-stenting with final kissing balloon post-dilatation (20 patients, 12.2%) was used more often than other techniques. During the PCI procedure, hemodynamic support by IABP and glycoprotein IIb/IIIa receptor antagonist were used more commonly in patients with significant RCA disease (Table 2). As for the treatment for RCA lesion, totally 72 patients underwent PCI (76%), with 21 patients undergoing PCI before LM stenting and 51 patients undergoing PCI later. Early and long-term outcomes Table 3 summarizes 30-day and long-term clinical outcomes after LM PCI. Within the 30-day period after index procedure, MACE was observed in 16 (9.9%) patients, including 15 (9.3%) deaths and 1 non-fatal MI (0.6%). Three patients suffered from probable sub-acute stent thrombosis (1.8%) according to the definition of ARC criteria. Figure 1A shows the Kaplan-Meier survival curve of 30 days total mortality of patients with and without RCA disease. Of note, by univariate logrank analysis, the survival of LM patients with RCA disease was worse than that of those without (p < 0.01). In the stepwise multivariate Cox regression analysis, female gender, left ventricular ejection fraction < 40% and RCA disease were identified as the significant independent predictors of 30-day deaths and MACE (Table 4A). As for the long-term outcomes, the mean follow-up period was 2.5 years (range 1 month to 9.7 years, median 23.4 months). There were 38 deaths (23.6%), and 57 MACE (35.4%), which also included 10 non-fatal MI (6.2%) and 20 TVR (12.4%). One late probable stent thrombosis case occurred 266 days after the index procedure (cumulative probable stent thrombosis cases: 4, Table days and long-term outcomes Outcomes 30 days Long-term Death 15 (9.1%) 38 (23.2%) CV death 09 (5.5%) 16 (9.8%)0 Stroke - 3 (1.8%) Non-fatal MI 01 (0.6%) 7 (4.3%) TVR - 19 (11.6%) MACE (death, nonfatal MI, TVR) 16 (9.8%) 56 (34.1%) Definite/Probable stent thrombosis 03 (1.8%) 1 (0.6%) TVR, target vessel revascularization; MACE, major adverse cardiovascular events. Table 2. Procedural characteristics RCA(-) n = 69 RCA(+) n = 95 p value Lesion location, n (%) Ostial/shaft 18 (27.1%) 24 (25.3%) Bifurcation 51 (73.9%) 71 (74.7%) Stent length (mm) Stent diameter (mm) DES for LM 31 (44.9%) 47 (49.5%) Bifurcation LM stenting Cross-over tech with 1 stent 42 (60.9%) 61 (64.2%) Technique with 2 stents T-stenting, n (%) 09 (13.0%) 11 (11.6%) Crush, n (%) 1 (1.4%) 4 (4.2%) Culottes, n (%) 4 (5.8%) 5 (5.3%) V stenting, n (%) 1 (1.4%) 2 (2.1%) Kissing post-dilation 26 (37.9%) 37 (38.9%) Use of Gp IIb/IIIa Inhibitors 07 (10.1%) 24 (25.3%) Use of IABP 6 (8.7%) 22 (23.2%) IVUS guidance 6 (8.7%) 10 (10.5%) Rotablation 2 (2.9%) 9 (9.5%) Gp, glycoprotein; IABP, intraaortic balloon pump; IVUS, intravascular ultrasound. 17 Acta Cardiol Sin 2011;27:14 20

5 Tse-MinLuetal. A B Figure 1. Kaplan-Meier analyses demonstrating proportion of patients without death during 30 days after index procedure (A) and long-term follow-up (B). Patients are divided into the presence and absence of RCA disease. Both p values were < Table 4. Multivariate Cox regression analyses of 30-day and long-term outcomes (A) 30-day outcomes Death MACE Variables HR (95% CI) p value HR (95% CI) p value Sex-female 09.1 ( ) < ( ) RCA disease 16.0 ( ) ( ) LVEF < 40% 61.4 ( ) < ( ) < (B) Long-term outcomes Variables Death MACE HR (95% CI) p value HR (95% CI) p value CRF 2.7 ( ) ( ) Cardiogenic shock 4.0 ( ) RCA disease 3.0 ( ) ( ) LVEF<40 % 3.8 ( ) ( ) < Use of IABP ( ) Use of DES ( ) CRF, chronic renal failure; LVEF, left ventricular ejection fraction; IABP, intraaortic balloon pump; DES, drug-eluting stent. 2.4%). Figure 1B shows the Kaplan-Meier survival curve of long-term total mortality of patients with and without RCA disease, respectively, and again, the survival of LM patients with RCA disease remained worse than that of those without (p < 0.01). If we narrowed the definition of significant RCA stenosis to more than 70% stenosis, the results of survival analysis for short-term and long-term outcomes were nearly the same (both p < 0.01). In the stepwise multivariate Cox regression analysis for independent predictors of total death, as shown in Table 4B, RCA disease was identified again as one of the independent predictors, as were left ventricular ejec- Acta Cardiol Sin 2011;27:

6 RCA Disease and Unprotected LM Stenting tion fraction < 40%, cardiogenic shock, and chronic renal failure. As for the composite endpoints of MACE, significant RCA disease remained an independent risk factor (Table 4B). Intriguingly, the use of IABP and DES for the LM PCI were identified as a predictor and protective factor for long-term MACE, respectively. However, the prognosis of patients with ostial/mid-shaft lesion was not better than that of those with distal bifurcation LM disease. Moreover, the adoption of 1-stent strategy was not associated with better outcome than the more complex 2-stent strategy. DISCUSSION The results of this study showed that in real-world practice, unprotected LM stenting appeared to be feasible and offered an acceptable long-term outcome in such a wide-ranging but high-risk population, although with a relatively high 30-day death and MACE rate. Patients with concomitant significant RCA stenosis seemed to carry a worse early and long-term prognosis. Although CABG remains the gold-standard treatment of LM CAD, several recent studies showed that LM PCI, especially by using drug-eluting stent, may be an alternative treatment for these patients, 1-11 and recently updated ACC/AHA guidelines have stated that PCI treatment for unprotected LM disease has a IIb-class recommendation. 12 As a critical part of left coronary circulation, left main coronary intervention carries an inherent substantial risk. Transient ischemia and shortperiod occlusion by balloon catheter inflation and implantation of stent, and even manipulation of guidewires, balloon catheters and stents may sometimes cause severe depression of left ventricular function, protracted hemodynamic compromise and even shock and catastrophic complications. In addition, recent introduction of complex stenting techniques for distal bifurcation of LM coronary artery, such as culottes stenting and crush technique may be time-consuming and markedly escalate the procedural risk. Although recent large reports about the real-world practice of unprotected LM stenting showed favorable short-term and long-term results, PCI over LM remains a technique challenge in patients with depressed left ventricular function and the presence of significant RCA narrowing. Likewise, PCI for RCA stenosis is also challenging in the presence of significant LM disease. Therefore, it is reasonable that the presence of significant RCA stenosis may have a negative impact on the short-term outcome, and study to find the optimal treatment for concomitant LM plus RCA disease may be warranted. On the other hand, in addition to short-term outcome, our results showed that the long-term outcome was also worse in the presence of RCA disease. The presence of concomitant RCA disease may actually indicate more extensive coronary atherosclerosis, which may be one of the possible underlying explanations. Moreover, restenosis of LM lesion after PCI is more likely to lead to disastrous event in the presence of significant RCA stenosis. On the other hand, elective support of IABP may prevent intra-procedural events in elective unprotected LM stenting, especially in patient at higher risk, namely EuroSCORE However, our results showed that IABP support was an independent predictor in long-term events. This may be related to the different characteristics of our study population, which was composed of more ACS cases with high-risk profile. Moreover, the use of IABP was at the discretion of different operators and was relatively limited in our study. The impact of IABP support on short-term and long-term outcomes may need to be investigated in larger study. In accordance with previous studies, 5,16 our data showed that the use of drug-eluting stent in unprotected LM PCI was associated with more favorable long-term outcome, leading to less total mortality and MACE. However, the involvement of distal LM and complex stent strategy using 2 stents or more were not related to the occurrence of more MACE, contrary to the results of a recent larger study 17 but similar to the results of the LE MANS registry. 7 This might be caused by relatively more cases with LM ostial/mid-shaft presenting as acute coronary syndrome in our study population (25/40, 62.5%), making the potentially worse prognosis in cases with distal LM bifurcation involvement not so significant. There are several limitations in this study. First, these findings derived from a single-center observation based on patients with higher surgical risks. In addition, significant RCA disease was also much more common in our population, compared to 17-44% of RCA disease in previous studies. 2,16,18 The outcome of patients with concomitant LM and RCA disease may be different in other lower-risk populations. Second, since our patients re- 19 Acta Cardiol Sin 2011;27:14 20

7 Tse-MinLuetal. ceived clinically-driven follow-up coronary angiography which were done in only about one-half of patients (72 patients, 49.3%), potential incomplete angiographic follow-up related bias can not be excluded completely. CONCLUSION In this real-world practice in a single center, we found that unprotected LM stenting in patients with concomitant significant stenosis of the RCA may be associated with worse early and long-term outcomes compared with those without RCA disease. REFERENCES 1. Chieffo A, Stankovic G, Bonizzoni E, et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation 2005;111: Valogimigli M, van Mieghem CAG, Ong ATL, et al. Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: insights from the rapamycin-eluting and taxus stent evaluated at Rotterdam cardiology hospital registries (RESEARCH and T-RSEARCH). Circulation 2005;111: Buszman PE, Buzman PP, Kiesz S, et al. Early and long-term results of unprotected left main coronary artery stenting: the LE MANS (left main coronary artery stenting) registry. JAmColl Cardiol 2009;54: Lee JY, Park DW, Yun SC, et al. Long-term clinical outcomes of sirolimus- versus paclitaxel-eluting stents for patients with unprotected left main coronary artery disease. J Am Coll Cardiol 2009;54: Seung KB, Park DW, Kim YH, et al. Stents versus coronaryartery bypass grafting for left main coronary disease. N Engl J Med 2008;358: Vaquerizo B, Lefevre T, Darremont O, et al. Unprotected left main stenting in the real world: two-year outcomes of the French left main taxus registry. Circulation 2009;119: Meliga E, Garcia-Garcia HM, Valgimigli M, et al. Longest available clinical outcomes after drug-eluting stent implantation for unprotected left main coronary artery disease: the DELFT (Drug Eluting stent for LeFT main) Registry. J Am Coll Cardiol 2008; 51: Tamburino C, Angiolillo D, Capranzano P, et al. Long-term clinical outcomes after drug-eluting stent implantation in unprotected left main coronary artery disease. Catheter Cardiovasc Intervent 2009;73: Rodés-Cabau J, DeBlois J, Bertrand OF, et al. Nonrandomized comparison of coronary artery bypass surgery and percutaneous coronary intervention for the treatment of unprotected left main coronary artery disease in octogenarians. Circulation 2008;118: Toyofuku M, Kimura T, Morimoto T, et al. On behalf of the j-cypher registry investigators. Three-year outcomes after sirolimus-eluting stent implantation for unprotected left main coronary artery disease: Insights from the j-cypher registry. Circulation 2009;120: Wang CC, Chen WJ, Tsai FC, et al. In-hospital and long-term results of unprotected left main stenting versus coronary artery bypass grafting a single center experience in Taiwan. Acta Cardiol Sin 2010;26: Kushner FG, Hand M, Smith SC, et al focused updates: ACC/AHA guidelines for the management of patients with STelevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association task Force on Practice Guidelines. J Am Coll Cardiol 2009:54: Nashef SA, Roques F, Michel P, et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16: Cutlip DE, Windecker S, Mehran R, et al. For the Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115: Briguori C, Airoldi F, Chieffo A, et al. Elective versus provisional intraaortic balloon pumping in unprotected left main stenting. Am Heart J 2006;152: Kim YH, Park DW, Lee SW, et al. Long-term safety and effectiveness of unprotected left main coronary stenting with drug-eluting stents compared with bare-metal stents. Circulation 2009;120: Palmerini T, Sangiorgi D, Marzocchi A, et al. Ostial and midshaft lesions vs. bifurcation lesions in 1111 patients with unprotected left main coronary stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology. Eur Heart J 2009;30: Capodanno D, Salvo ME, Cincotta G, et al. Usefulness of the SYNTAX score for predicting clinical outcome after percutaneous coronary intervention of unprotected left main coronary artery disease. Circ Cardiovasc Intervent 2009;2: Acta Cardiol Sin 2011;27: