Significant left main coronary stenosis occurs in 5–7% of patients undergoing coronary angiography.1,2 Patients with “unprotected” left main coronary artery (ULMCA) disease treated medically have an estimated 3-year mortality rate of 50%.3,4 Since clinical trials have consistently demonstrated a survival benefit of coronary artery bypass graft (CABG) surgery over medical therapy,5,7 the current standard of care for treatment of ULMCA stenosis is CABG surgery.
Percutaneous coronary intervention (PCI) of ULMCA is associated with a high rate of early restenosis (especially when the procedure involves the distal left main bifurcation). Since acute thrombotic occlusion and mortality were reported in earlier clinical studies, the American College of Cardiology and American Heart Association have discouraged elective PCI for ULMCA.8
**i*With the evolution of PCI methodology and technology and operator experience, these guidelines have been challenged. Currently, the preferred method for revascularization of ULMCA stenosis is subject to randomized clinical trials. For years, the standard of care in cases with ULMCA stenosis in the acute setting has been revascularization by CABG, which has generally shown good results, especially since the routine use of mammary grafts.
Recent observational data suggested that ULMCA PCI with sirolimus-eluting stents (Cypher™, Cordis Corp., Miami, Florida) and paclitaxel-eluting stents (Taxus®, Boston Scientific Corp., Natick, Massachusetts) may favorably affect restenosis rates.9–11 A contemporary report comparing CABG with PCI for ULMCA disease concluded that despite a higher percentage of high-risk patients in the PCI arm, PCI of ULMCA disease was not associated with an increase in immediate- or intermediate-term complications compared with CABG.12
The evolution of percutaneous transcatheter technology, including guide catheters, guidewires, low-profile balloons and stents, hemodynamic support, periprocedural lesion imaging, and adjunctive pharmacotherapy, has led interventionalists to the decision to attempt PCI in certain subsets of patients with ULMCA stenosis. Although lesions in the ostium and body of the LMCA were tackled successfully with contemporary stents, distal (bifurcations) lesions, especially when calcified, remained risky and skill-demanding procedures.
We report a single-center experience with ULMCA stenting in urgent and emergent clinical settings. Both the acute and long-term results are presented and analyzed in comparison to a clinically matched cohort that underwent CABG.
Study population. Between July 2003 and March 2005, 51 patients were referred for urgent or emergency cardiac catheterization and found to have ULMCA stenosis or occlusion requiring immediate revascularization. All patients underwent immediate PCI and were followed up clinically to record major adverse cardiovascular and cerebrovascular events (MACCE): death, nonfatal myocardial infarction, stroke and ischemia-driven target vessel revascularization in-hospital, at 30 days, and at 6 and 12 months.
In parallel, a contemporary group of 35 clinically matched patients who were referred for CABG in a similar urgent or emergent clinical context were also followed up for 30 days, 6 and 12 months for MACCE. The decision to refer patients for CABG was made by the operator.
We defined left main coronary artery disease as unprotected if there was absence of functioning grafts to the left anterior descending artery and/or to the left circumflex coronary artery. Because of the urgent/emergent nature of the procedures, patients were not prescreened by a cardiac surgeon for CABG eligibility. This was a nonrandomized, prospective, open-label study and was approved by the local institutional review board. Informed, written consent was obtained from all patients or their authorized closest family members.
PCI was performed using the standard percutaneous transfemoral approach except in 1 patient who underwent PCI via the transradial approach due to extensive peripheral vascular disease. Lesions at the ostium or the body of the ULMCA without distal bifurcation involvement were usually treated with a single stent. Several techniques were used for the treatment of distal bifurcation disease: stenting across the left circumflex or the left anterior descending coronary arteries (the “crossover technique”) with provisional stenting of the nonstented artery, simultaneous kissing stenting, modified T-stenting, and the “crush technique”, as previously described.13,14
The choice of stent size, brand and category (bare-metal or drug-eluting stent), and the adjunctive pharmacotherapy regimen were at the operator’s discretion. High-pressure stent deployment was performed using an initial inflation ≥14 atm. In the majority of cases, intravascular ultrasound (IVUS) was used to confirm optimal stent apposition and expansion. If necessary, postdilatation with additional noncompliant balloons was performed.
Glycoprotein IIb/IIIa antagonists were used in all patients, and an intra-aortic balloon pump was used when clinically indicated. On admission to the ICCU, all patients received aspirin 325 mg and a loading dose of 300 mg of clopidogrel. Aspirin was continued indefinitely and clopidogrel was continued for at least 6 months.
Follow up. Patients were followed clinically at 1 and 6 months. In addition, patients were requested to undergo a follow-up coronary angiography at 6 months.
Quantitative coronary angiography data (QCA). Quantitative analyses of all angiographic data were performed with the use of edge-detection techniques (CASS II, Pie Medical, The Netherlands). A value of 0 mm was assigned for the minimum luminal diameter (MLD) in cases of total occlusion at baseline or follow up. Binary restenosis was defined as ≥50% stenosis when compared to proximal, or rarely, distal reference segment. Acute luminal gain was defined as the MLD after the index procedure minus the MLD at baseline angiography. Late loss was defined as the MLD immediately after the index procedure minus the MLD at angiographic follow up. Quantitative angiographic measurements of the target lesion were obtained in-stent and in-segment (including the stented segment as well as the margins 5 mm proximal and distal to the stent when feasible).
Definitions. PCI procedural success was defined as Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 at the end of the procedure, with a final residual stenosis <10% by QCA in the absence of death or emergency CABG prior to hospital discharge.
Death was defined as any postprocedure death during the follow-up period. Target lesion revascularization was defined as a repeat revascularization to treat a stenosis within the stent or 5 mm distal and/or proximal segments adjacent to the stent, including the ostium of the left anterior descending artery and/or left circumflex artery. A cerebrovascular event was defined as any stroke, transient ischemic attack, reversible ischemic neurologic deficit or coma.
The Parsonnet score was used to stratify the risk of death at 30 days.15,16 A Parsonnet score >15 identified patients at high risk for surgical mortality.
Statistics. Continuous variables are presented as mean ± standard deviation (SD). The Satterthwaite adjustment was applied to the Student’s t-test when there was evidence against equality of variance.
The chi square test was used to determine the significance of differences in categorical variables. Survival curves were generated by the Kaplan-Meier method. Survival analysis was performed for the first 400 days. A multivariate Cox proportional hazard model was created with the use of baseline clinical and angiographic characteristics and procedure-related variables in order to identify independent predictors of MACCE.
Baseline clinical characteristics. Baseline and procedural characteristics are listed in Table 1. Patients with ULMCA disease tended to be old (>75 years of age), with an average Parsonnet score of 16.4 ± 9.3 on presentation. In concordance with this finding, the majority of patients presented with two or more risk factors with a prevalence of diabetes mellitus in 41% of the cases, hypertension in 72%, and chronic renal failure (creatinine >2) in 4%. The average left ventricular ejection fraction (LVEF) was 40% ± 12%. Only 12 patients (23%) showed no additional significant lesions in the coronary tree.
Six patients underwent PCI (12%), and after initial stabilization, were referred for CABG because of significant coronary artery disease not amenable to PCI. All patients with ostial or mid-ULMCA disease received only a single stent. Distal disease involving the bifurcation was present in 27 patients (53%), and 16 of these patients (59%) required more than 1 stent.
Clinical presentation (Table 2). The majority of patients presented with Q-wave myocardial infarction (MI) (65%), while 19% presented with unstable angina associated with high-risk characteristics (electrocardiographic changes and elevated troponin I). Cardiogenic shock was present in 10 patients.
Angiographic and lesion characteristics (Table 3). Twenty-seven patients (53%) showed bifurcation lesions involving the distal LMCA and the ostium of the LAD and LCX. Angiographically visible thrombus-containing lesions were seen in 23% of the cohort and the calcification score exceeded a moderate level in 24% of the patients.
Procedural characteristics and outcomes (Table 4). The procedural success rate was 98%. Intra-aortic balloon pump was used in 50 patients (98%). Only 10 patients (19%) underwent PCI with drug-eluting stents.
On average, 2.3 ± 1.2 stents per patient were implanted, with a total stent length of 24 ± 10 mm. In 53% of the study population, the disease was located at the bifurcation also involving the ostium of the LAD and the ostium of the LCX. In this group of 27 patients, 13 underwent a PCI technique that involved stenting of the ULMCA toward the LAD or the LCX, with provisional stenting of the side branch and final kissing balloon (crossover technique); in 9 patients with large left main coronary arteries, we used the V-stenting technique or simultaneous kissing stent (SKS); in 4 patients with appropriate anatomy, the modified T-stenting technique was implemented; and in 1 patient, the crush technique using the LAD as the main vessel was implemented.
Thirty-day outcomes. There were no cerebrovascular events in this cohort at 30-day follow up. The mortality rate at 30 days was 8%. There were 4 deaths: 2 were due to cardiac reasons (1 very late arrival and 1 from intractable ventricular fibrillation several hours after the procedure); 1 patient had a Parsonnet score of 41 and was considered a high-risk candidate for CABG; and 1 patient was admitted 2 days after peripheral vascular surgery with an extensive anterior ST-elevation MI. No patient required urgent target vessel revascularization (TLR).
One patient developed cardiac tamponade requiring emergent pericardiocentesis secondary to a pacemaker electrode perforation, which resolved without sequelae. No patient developed acute renal failure requiring hemodyalysis or experienced vascular complications such as major hematoma requiring blood transfusion or pseudoaneurysm. No patient required surgical repair at the access site.
Six-month and one-year clinical and angiographic follow up. The mean clinical follow-up time was scheduled at 11 ± 4 months. The estimated MACCE-free survival rate at 6 months and 1 year was 90% and 88%, respectively (Figure 1). The estimated freedom from death at 6 months and 1 year was 97% and 97%, respectively (excluding 4 deaths occurring within 30 days of the index procedure).
Angiographic follow up was available in 12 patients (24%). The main reason for this low angiographic follow-up rate was refusal of patients to undergo repeat catheterization. QCA data from these 12 patients showed an in-stent late loss of 0.30 ± 0.15 mm, and an in-segment late loss of 0.22 ± 0.20 mm. There was no angiographic binary restenosis. Freedom from TLR at 6 months and 1 year was 97% and 94%, respectively. All 3 patients who underwent repeat PCI had distal bifurcation involvement. One of these 3 patients returned with restenosis and was referred for CABG. Regarding lesion location, despite a similar LMCA reference vessel diameter, patients with distal disease involving the bifurcation tended to have a longer lesion length and a slightly smaller MLD at angiographic follow up compared with target lesions located at the ostium or body of the LMCA. In-stent and in-segment acute luminal gain appeared to be similar, whereas late loss was higher in patients presenting with distal disease with no statistical significance (0.22 ± 1.2 mm versus 0.41 ± 1.5 mm; p = 0.09) and no need for additional procedures. The estimated rate of freedom from death, MI and cerebrovascular events at 6 months and 1 year was 97% and 97%, respectively.
Multivariable analysis (Table 6). In the final Cox model, the significant predictors of the hazard of MACCE were Parsonnet score (HR 1.93, 95% CI 1.15–7.3; p = 0.04) and diabetes mellitus (HR 1.73, 95% CI 1.03–3.8; p = 0.038)
The most relevant finding of our study is that treatment with PCI of unprotected left main coronary artery disease in the emergent/urgent clinical setting is associated with good clinical outcomes. Patients in this cohort showed high preoperative risk using traditional cardiac surgery criteria.
Up to the present, reports comparing PCI and CABG for ULMCA treatment have been in the context of elective patients with either low or high surgical risk characteristics. Studies comparing PCI with bare-metal stents to CABG in multivessel coronary artery disease reported no mortality benefit, although there were lower rates of repeat target vessel revascularization in the CABG cohort.17,18 However, the Arterial Revascularization Therapies Study II (ARTS II)19 comparing contemporary multivessel PCI with DES to a historic CABG control arm did not demonstrate an excess of repeat revascularization in the PCI arm. To date, it is still unknown whether the improved outcomes for PCI with DES will be extended to patients with ULMCA disease. An overview of 35 clinically well-matched surgical patients in our center showed that at 30 days, the cerebrovascular event rate was 6%, the perioperative MI rate was 2%, and 30-day and 6-month mortality rates were 6% and 12%, respectively. This is consistent with the published data on CABG for ULMCA. The Cleveland Clinic Foundation reported 2.3% in-hospital and 11% 1-year mortality in a similar clinical setting.20 The present observational study suggests that in the ULMCA subset of patients in the urgent/emergent setting, PCI provides an equivalent or lower rate of death, MI and cerebrovascular events with an overall MACCE rate of 6%. An analysis of the surgical cohort showed an overall MACCE of 17%. Cerebrovascular events were the main reason for the increase in MACCE in the surgical group.
The ongoing prospective Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) and Revascularization Comparing Surgery versus Percutaneous Coronary Intervention for Unprotected Left Main Coronary Stenosis Randomized Evaluation (REVASCULARIZE) trials will add more needed data on the relative merit of PCI in ULMCA, and especially regarding distal (bifurcation) ULMCA PCI. Even in this small cohort, we found differences between distal left main disease and nondistal left main disease, with a trend toward more late loss and less net gain in the former group. All three of the cases of target vessel revascularization were in patients with distal bifurcation disease involving the ULMCA. This observation is in congruence with the Rapamycin-Eluting Stents Evaluated at Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registries, suggesting that lesions located at the distal left main segment involving the bifurcation emerged as a major predictor of poor long-term outcome, independent of the patient’s overall surgical risk status.21 These authors conclude that lesion location could be an important tool for risk stratification for patients undergoing catheter-based treatment of ULMCA.
PCI in distal bifurcation ULMCA is associated with a high restenosis rate at the ostium of the left circumflex artery.9–11 Virmani et al reported in pathological studies of bifurcation lesions that arterial branch points are predisposed to the development of atherosclerotic plaque, thrombus, and inflammation due to low-shear and low-flow velocities.22
1) The study includes a small cohort of heterogenous patients and is not a randomized trial.
2) The study has a lack of long-term follow up regarding in-stent restenosis, especially in those patients treated with bare-metal stents.
3) A low percentage of the patients underwent angiographic follow up.
4) Only a minority of patients received drug-eluting stents, which may not represent contemporary ULMCA PCI.
In this observational study, PCI for ULMCA disease appeared to be a viable alternative to CABG in the urgent/emergent clinical setting, showing low short- and long-term MACCE. Distal ULMCA (true bifurcation) disease emerged as a negative predictor of long-term outcome. This reinforces the need for large-scale randomized studies using drug-eluting stents and long-term follow up to provide the basis for risk stratification of patients undergoing catheter-based treatment of ULMCA disease in the nonelective clinical setting. Moreover, it points to the need for dedicated “bifurcation stents” and drug-eluting bifurcation stents.
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