Isolated Disease of the Ostium Left Anterior Descending or
Circumflex Artery: Management Using a Left Main Stenting
Technique.
Treatment of isolated coronary stenoses involving the ostium of the left anterior descending (LAD) or circumflex (LCX) artery is challenging for the interventionalist. Although focal stenting is often attempted, it may result in incomplete lesion coverage or protrusion of the proximal stent margin into the ostium of the adjacent vessel. Furthermore, plaque shift with compromise of the adjacent vessel is a potential complication.1,2 Because of these concerns, many patients with this type of disease are referred for coronary artery bypass graft surgery (CABG).
Since compromise of both left coronary vessels may occur with stenting, ostial disease of the LAD or LCX represents a type of left main disease, originally classified by Lefevre et al as Type 4A left main bifurcation lesion.3 Several studies have demonstrated a low in-hospital complication rate with unprotected left main stenting.4–7 Further, early follow-up results of left main stenting are encouraging.8
We hypothesized that ostial disease of the LAD or LCX would ideally be treated percutaneously by stenting from the left main into the diseased main branch with provisional sidebranch stenting. This strategy would result in complete lesion coverage while protecting the adjacent vessel. The purpose of the present study was to evaluate the results of this technique.
Methods
This prospective study was conducted in a high-volume cardiovascular center between January 2003 and February 2006. All consecutive patients with significant angiographic de novo, unprotected, isolated ostial LAD or LCX artery stenoses were identified and screened for study eligibility. An ostial stenosis was defined as an isolated angiographic narrowing of ≥ 75% located within 3 mm of the vessel origin: Type 4A or 4B lesion according to the Institut Cardiovasculaire Paris Sud bifurcation classification, and a 0,1,0 or 0,0,1 according to the Medina classification.3,9 Patients with a side branch angiographic stenosis ≥ 50% were specifically excluded from the study.
Inclusion criteria required that patients be symptomatic with either stable or unstable angina or documented myocardial ischemia with stress testing. Patients with acute myocardial infarction (AMI), previous CABG, contraindication to antiplatelet therapy, significant involvement of other coronary vessels, cardiogenic shock or chronic total occlusions were excluded from the study. Treatment options were fully discussed with the patient and informed consent was obtained. The study protocol was approved by the institutional review committee.
Interventional technique. All patients were pretreated with aspirin 325 mg and clopidogrel 600 mg. Anticoagulation with intravenous heparin, with or without glycoprotein (GP) IIb/IIIa inhibitors or weight-adjusted bivalirudin, was left to the discretion of the operator. Access site and predilatation using balloon angioplasty or debulking atherectomy were also discretionary, although a strategy of direct stenting was preferred. The bifurcation technique of stenting the main branch with provisional side branch stenting was employed.10 The stent was deployed from the distal portion of the left main across the ostium of the adjacent vessel into the diseased vessel, ensuring complete lesion coverage (Figure 1B). After guidewire exchange, kissing balloon inflations were performed (Figure 1C). Provisional stenting of the side branch was employed only if a residual dissection or significant plaque shift was observed or resulted in angiographic side branch stenosis of ≥ 50%. Drug-eluting stents (DES) (Taxus®, Boston Scientific Corp., Natick, Minnesota or Cypher™, Cordis, Johnson and Johnson, Miami Lakes, Florida) were used in all cases. Balloon and stent sizes were selected according to the distal reference vessel size. Combined antiplatelet therapy with aspirin 325 mg and clopidogrel 75 mg was continued for a minimum of 12 months after the procedure in all patients according to recent guidelines.11
Follow up. Patients were followed clinically by either telephone calls or office visits at 30 days, 6 months, 1 and 2 years after the index procedure. Follow-up coronary angiograms with intravascular ultrasound (IVUS) were performed at 9 to 12 months, or earlier if clinically necessary.
Study endpoints and definitions. The primary endpoint of the study was the occurrence of any major adverse cardiac event including death, non-fatal AMI, or target lesion revascularization (TLR) during the initial procedure or during the follow-up period. Angiographic procedural success was defined as a Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and a < 30% residual diameter stenosis. The diagnosis of AMI required an elevation of serum creatine kinase-MB fraction > 3 times the upper limit of normal. TLR was defined as either CABG or percutaneous reintervention for restenosis (> 50%) occurring within the stent or the 5 mm borders proximal and distal to the stent. The patient’s operative risk was assessed using the EuroSCORE.12,13 Procedure duration was defined as the time interval between insertion of the first catheter and removal of the last guidewire. Fluoroscopy time included the diagnostic procedure for ad hoc interventions.
Quantitative coronary angiographic evaluation. Quantitative coronary angiographic (QCA) measurements were obtained in all patients. The guiding catheter was used as the calibration reference. Measurements were performed at the following points: (1) baseline; (2) postprocedure; and (3) follow-up angiography. According to conventional practice, the main branch vessel was determined by the location of the lesion. The QCA variables analyzed included: (a) lesion length; (b) reference vessel diameter (RVD); (c) minimal lumen diameter (MLD); (d) percent diameter stenosis; (e) acute luminal gain (MLD immediately after the procedure minus the MLD before the procedure); (f) late lumen loss (MLD immediately after the procedure minus the MLD at follow up); and (g) restenosis (stenosis > 50% of the luminal diameter at follow up). The vessel segment immediately following the main branch ostial lesion was used as the RVD.
Statistical analysis. Data are expressed as mean ± standard error of the mean or as percentage with a 95% confidence interval. The unpaired student’s T-test and chi-square test were utilized to compare continuous variables and categorical variables, respectively. Cumulative event-free survival rates were evaluated according to the Kaplan-Meier method.
Results
Thirty-three patients (19 males, 14 females) with a mean age of 67 years (range 47–86) were included in the study. Baseline demographic characteristics are shown in Table 1. The majority of patients had stable coronary disease and were considered at moderate risk for cardiac surgery according to a mean EuroSCORE of ≥ 4.2 ± 0.5. The prevalence of diabetes was 39%, and the mean left ventricular systolic ejection fraction was 53%.
All patients were successfully treated during the index procedure using 6 Fr guiding catheters. Procedural and angiographic characteristics are summarized in Table 2. The radial approach was utilized in 64% of procedures, and the mean procedure duration was 41 ± 4 minutes. The mean fluoroscopic time was 22 ± 2 minutes. The LAD was the main branch vessel in 76% of patients. Predilatation with balloon angioplasty was performed in 42% of patients, and directional atherectomy was employed in 1 patient. Taxus stents were used in 85% of cases. The average stent diameter was 3.7 mm, and the average stent length was 17 mm. Provisional side branch stenting was carried out in 9 (27%) patients. GP IIb/IIIa inhibitors were used in 6 (18%) patients.
Clinical follow up was obtained in all patients at a mean interval of 24 months. During this period, 1 cardiac death (3%) and 1 non-fatal MI (3%) occurred (Table 3). Protocol-driven routine follow-up angiography with IVUS was available in 30 (91%) of the patients at a mean interval of 11 months. TLR due to restenosis was performed in 5 (15%) of the 33 total patients. In 2 of the 5 patients, restenosis occurred at the proximal margin of the main branch stent. In 3 of the 5 patients, restenosis occurred within the side branch; of these, 2 patients had undergone provisional side branch stenting. Restenosis within the confines of the main branch stent did not occur. The overall event-free survival rate was 79% at 2 years (Figure 2).
QCA results. Angiographic results from QCA data analysis are shown in Table 4. The mean RVD was 2.9 ± 0.1 mm,with a mean target lesion length of 7 ± 0.6 mm. Baseline ostial stenosis was 62%. Main branch stenting resulted in acute luminal gain of 1.6 ± 0.1 mm. Follow-up angiography at a mean interval of 11 months revealed late lumen loss of 0.19 ± 0.04 mm. Binary restenosis did not occur within the main branch stent. Late lumen loss in the side branch was 0.3 ± 0.1 mm, and restenosis occurred in 3 (9%). Late lumen loss in the left main artery was 0.4 ± 0.1 mm, and restenosis occurred at the proximal stent margin in 2 (6%).
Discussion
The major finding of this study is that isolated disease at the ostium of the LAD or LCX can safely be treated using a left main bifurcation technique. Stenting from the left main into the diseased vessel results in complete lesion coverage and final kissing balloon inflations manage plaque shift and open stent struts to maximize blood flow into the adjacent “jailed” vessel. One death occurred within a mean followup period of 24 months, and TLR was required in 15% of patients.
Disease at the ostium of the LAD or LCX presents unique technical concerns for the interventionalist. Complete lesion coverage with precise stenting invariably will result in positioning the proximal portion of the stent in the ostium of the adjacent vessel with uncertain sequelae. Furthermore, plaque shift during main branch balloon inflations may compromise the adjacent vessel (the snow-plough effect).14 Negative vascular remodeling may also result in progressive late narrowing of the adjacent vessel.15–17 Thus, ostial disease of the LAD and LCX behaves as a left main lesion when approached interventionally. Indeed, Lefevre et al classified this type of disease as a Type 4a left main lesion.3
Several recent studies have documented the safety of left main stenting with DES and early follow-up results have failed to show excessive morbidity or mortality.6–8 Main branch stenting followed by kissing balloon inflations and provisional T-stenting of the side branch currently is the preferred technique for bifurcation stenting including the left main location.18,19 Seung et al adopted this strategy in 23 patients with ostial LAD disease and had no restenosis at 6- month follow up.20 In comparison, focal stenting also had a low incidence of inhospital MACE and TLR at 6–9 months.21
In the present study, in-hospital MACE was low with no deaths and only 1 non-Q-wave MI. Provisional T-stenting of the side branch was performed in 27% of patients. Subsequent follow up at a mean interval of 24 months revealed restenosis in 5 (15%) patients who underwent TLR (4 patients underwent repeat percutaneous intervention and 1 patient underwent CABG). The pattern of restenosis is noteworthy. Restenosis within the confines of the main branch stent itself was not seen. Three patients (9%) developed restenosis at the ostium of the side branch. Two patients (6%) developed restenosis at the proximal main branch stent margin within the left main artery. Whether final kissing balloon inflations was an etiological factor in this restenosis is a conjecture, but the importance of keeping balloon inflations within the confines of a deployed stent in order to minimize such intimal damage at the stent margin has previously been emphasized.22,23
The management of ostial LCX disease in the present study warrants attention. Stenting across the LAD is controversial due to the large amount of myocardium jeopardized both from plaque shift and “jailing” stent struts. Little information is found in the literature for comparison. The final kissing balloon and provisional stent strategy minimized the risk of this strategy. Although no in-hospital events occurred in this group, 1 patient had restenosis at the ostium of the LAD at follow-up angiography, thus routine follow-up angiography should be performed in these patients.
The uncertainty of the long-term consequence of DES used in off-label sites such as the left main coronary artery raises an important concern about the present study.24 Currently, the available data suggest no safety concerns, but late stent thrombosis of DES remains an issue because of the dire potential complications of left main stent occlusion. Thus, it is currently our recommendation that these patients be maintained on clopidogrel indefinitely.
Study Limitations
An important limitation of the present study is that it is a single-center registry of a small number of nonrandomized patients. Despite long-term follow up in all patients, the ideal management of ostial LAD and LCX stenoses will ultimately be determined by a multicenter trial in which patients are randomized between the present technique, CABG and precise stent deployment using IVUS with and without pre-stent deployment debulking techniques.
It should be emphasized that the present data are from a “real-world” registry conducted by experienced operators in a high-volume interventional center. Several variables present in our study including stent type, anticoagulation regimen and arterial access site were discretionary, and this could affect the study’s results. In addition, patient variables such as diabetes and other comorbid disease may alter outcomes. Finally, routine IVUS before stent placement may provide useful information, and this was not performed in the present study.20
Conclusion
In conclusion, DES deployment using a left main bifurcation technique for isolated ostial LAD and LCX disease may be a reasonable option in these patients.
References
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