Balloon Alignment T-Stenting for Bifurcation Coronary Artery Disease Using the Sirolimus-Eluting Stent

Compared to the use of bare-metal stents (BMS), drug-eluting stents (DES) have been shown to reduce the rate of restenosis in bifurcation coronary artery disease.¹ Specifically, the segment demonstrating the greatest susceptibility to restenosis when using multiple stents is the ostium of the side branch.² It has been shown that this propensity for ostial side branch restenosis occurs for a variety of reasons: gaps in vessel coverage between stents at the carina of the lesion, protrusion of the side branch stent into the main branch, as well as stent distortion following final balloon postdilatation have all been implicated.³ A variety of innovative techniques using the current DES platforms have been developed (crush, kissing, skirt, trouser and T-stenting),^4–6 but published data reflect technical shortcomings with higher rates of long-term target lesion revascularization (TLR) compared to nonbifurcation disease.⁷ The purpose of this pilot study therefore was to evaluate the, safety, feasibility and intermediate-term luminal patency of a novel stenting technique utilizing the Cypher® sirolimus-eluting stent (SES) (Cordis Corp., Miami, Florida). Specific attention was given to the side branch ostium. Balloon alignment T-stenting has been the focus of several previous publications addressing the management of bifurcation coronary artery disease.^8,9Materials and Methods Study population. This study was a prospective, nonrandomized, open-label, single-center trial evaluating the safety and feasibility of balloon alignment T-stenting for bifurcation coronary disease. All 26 patients treated in this pilot trial had de novo coronary disease, with no previous interventions having been performed on the target vessels. Patients were eligible for enrollment who had stable or unstable angina (Braunwald classification 1–2 A, B), or those proven to have ischemia based on noninvasive testing. Male or female patients with significant coronary artery disease confined to the left anterior descending (LAD)/diagonal artery distribution requiring stent placement were eligible for enrollment in the study. Patients included also demonstrated visual assessment of a main branch reference vessel diameter of greater than or equal to 2.5 mm to less than or equal to 4.5 mm, and a side branch reference vessel diameter of greater than or equal to 2.0 mm. Major exclusion criteria were the presence of thrombus in the target vessel, severe tortuosity or calcium in the target vessel, or the presence of significant left main disease. Lesions were required to have > 50% luminal diameter narrowing as determined by angiography. There were no exclusions based on lesion length. Preprocedure. Prior to enrollment in the study, prescreening and baseline tests were performed. All patients received a preprocedural physical examination, including medical history, laboratory evaluations and electrocardiogram (ECG). A diagnostic angiogram was performed to document the presence of high-grade, bifurcation LAD/diagonal coronary artery disease. Prior to the procedure, all patients were pretreated for a minimum of 48 hours with 325 mg aspirin daily, as well as clopidogrel 75 mg. The use of nitrates, calcium channel-blockers and beta-blockers was optional. At the time of the procedure, all patients were administered a standard dose of bivalirudin bolus, followed by a continuous infusion for the duration of the intervention. Stenting procedure. At the time of the procedure, coronary arteriography was performed to document the extent, morphology and location of the culprit bifurcation lesion. Intracoronary nitroglycerin was administered in order to measure the maximally dilated reference vessel. Reference vessel diameter (RVD) was determined using angiography and after injection of intracoronary nitroglycerin. After successful double-wiring of the involved vessels, the extent of balloon predilatation of both arteries was discretionary. Balloon alignment T-stenting is a multistep approach (Figures 1 A–F) involving an upfront double-wire technique on both the main branch and side branch of the bifurcation lesion. Following wire access of both branches, a stent in the side branch is aligned with a balloon in the main branch (1:1 balloon-to-artery ratio) in end-to-side fashion. Simultaneous inflation of the balloon in the main branch and the stent in the side branch is then performed to allow for ostial alignment of the side branch stent. Following deflation and retrieval of the main branch balloon and side branch stent delivery system, the side branch wire is removed and T-stenting across the side branch is performed. Re-entry of the side branch follows with final balloon or kissing balloon dilatation. Following the procedure, all patients underwent serial measurements of creatine kinase and MB fractions, as well as postprocedural electrocardiography. The Cypher SES was used in all patients for the purpose of this study. The use of glycoprotein IIb/IIIa inhibitors was discretionary. All patients were continued for 1 year on clopidogrel 75 mg and aspirin 325 mg. Six-month anniversary angiography was performed on all 26 patients in this pilot trial. Patient follow up. Following the procedure, routine CK-MB isoenzymes were evaluated at 8, 16 and 24 hours postprocedure. ECGs were performed at 4 and 24 hours postprocedure. Additionally, 6 to 9 months postprocedure, angiography was performed to determine stent patency. Endpoints and definitions. The aim of this pilot trial of balloon alignment T-stenting was to determine the safety and feasibility of this novel bifurcation technique. The primary endpoint was 6-month stent patency of both the main and side branches. Secondary endpoints included major adverse cardiac events (MACE) at 180 days, defined as death, Q-wave or non-Q-wave myocardial infarction (MI) and target lesion revascularization (TLR). Non-Q-wave MI was defined as creatinine kinase 3 times the upper limit of normal, with elevated MB fraction. Q-wave MI was defined as new pathological Q-waves in 2 or more leads in addition to elevated enzymes, as above. TLR was defined as the need for main and/or side TLR, either by coronary artery bypass grafting or by percutaneous coronary intervention. Target vessel revascularization (TVR) was defined as any vessel revascularization. Other secondary endpoints included technique success, overall procedural success (which was defined as 50% residual diameter stenosis in both the main and side branches by quantitative coronary angiography using the balloon alignment T-stenting technique, and freedom from MACE at the time of hospital discharge), MACE at 30 days, binary restenosis and target vessel failure at 6 months (composite of death, Q-wave or non-Q-wave MI and TVR). Angiographic analysis. Qualitative coronary analysis (QCA) was performed on the baseline diagnostic angiogram, postprocedural result and at 6-to-9 months following the original procedure. Binary restenosis was defined as geater than or equal to 50% diameter stenosis in the main branch and/or side branch using the QuantCor QCA System (Siemens AG, Erlangen, Germany) to conduct the quantitative coronary measurements. All cine angiograms were forwarded to a central angiographic core laboratory where they were analyzed by observers who were blinded to the clinical outcomes. QCA of native vessel morphology before and after stenting was performed using standard criteria and the modified American College of Cardiology/American Heart Associated lesion complexity score. QCA was performed using selected cine frames at baseline and at the end of the procedure using angiographic projections that demonstrated the stenosis in its worst severity with minimal vessel foreshortening or branch overlap. Intravenous nitroglycerin (100–200 µg) was administered in conjunction with each angiographic image acquisition. Using the injection catheter as the calibration standard, an automated edge-detection algorithm was used to calculate the reference vessel diameters (mm), the minimal lumen diameter (MLD mm) and percent diameter stenosis (% DS) before and after the procedure. Results This study represents a single-center pilot trial conducted between April, 2003 and December, 2005. All 26 patients enrolled had bifurcation lesions in the LAD/diagonal system. Twenty of the 26 patients treated were categorized as having a true bifurcation lesion (disease involvement at the carina of the lesion with contiguous extension into both the main branch and the side branch). There were a total of 26 LAD or main branch segments treated, with 27 diagonal vessels or side branches stented (1 patient actually had a trifurcation of the LAD, with 2 diagonal side branches treated). Baseline characteristics. Baseline patient epidemiologic descriptors of our patient population are seen on Table 1. The average age of our patient population was 61 years, with 23% having a history of diabetes. The average ejection fraction was approximately 58%. Though intended to be a study of de novo coronary disease, 15% of patients reported having a previous MI. However, for the purposes of this study, none of the lesions treated were the focus of a previous intervention. Lesion angiographic success was achieved in all 26 of the main branch lesions treated and all 27 side branch lesions treated. In no case of main branch or side branch stenting was a residual stenosis of greater than or equal to 50% left untreated. In 2 cases, “geographic miss” of the side branch ostium led to the use of a second stent in the side branch. Overall, a second stent was used in 15% of the 27 side branches treated and 38% of the main branch vessels stented (Table 2). Reasons for deployment of a second stent generally included geographic miss and lesion length. However, there were 2 cases in the main branch of an intimal disruption leading to additional stent implantation. Overall procedural success (residual stenosis Quantitative coronary angiography. At 6-month anniversary angiography (Table 3), 7.6% of the total 26 patients in the study were documented to have in-stent restenosis. However, there were no cases of main branch in stent restenosis and 2 cases of ostial side branch restenosis. Of the total 27 side branch lesions treated (including 1 case of trifurcating LAD/diagonal disease), 2 side branch ostia (7.4%) demonstrated significant in-stent disease at 6-month angiography. The total MACE rate (Table 4) for the 26 patients was 15.4%. As above, there were 2 side branch TLRs at 6-month angiography due to side branch restenosis, necessitating revascularization, and also 2 in-hospital non-Q-wave MIs documented. The aggregate target vessel failure rate was 19.2%. Acute gain, late lumen loss and minimal lumen diameter by quantitative coronary angiography are noted in Table 3. The late loss in the main branch and the side branch were 0.29 and 0.30, respectively. The average reference vessel diameter at baseline in the main branch was 3.20 mm and 2.50 mm in the side branch. Other baseline descriptors included and average diameter stenosis in the main branch of 65.9% and lesion length of 15.9 mm. The side branch average diameter stenosis was 59.9 mm and lesion length was 5.69 mm. Discussion It has been shown that provisional T-stenting, arguably the most widely accepted percutaneous therapy for bifurcation coronary disease, is associated with a number of technical shortcomings which can lead to restenosis, particularly at the side branch ostium.³ According to published studies, the side branch ostium is the segment most prone to stent underexpansion and restenosis.² Commonly described technical problems contributing to side branch vulnerability include gaps between stents when attempting to cover its ostium, “stent shift” following adjunctive balloon dilatation and distortion of the stent struts. Current standard techniques utilizing existing platforms have not adequately addressed these all-too-common procedural challenges. Balloon alignment T-stenting, as demonstrated in the present study, attempts to address these shortcomings with particular emphasis on eliminating gaps in stent coverage at the side branch ostium. This may be accomplished without the unintended consequences of stent distortion or interruption of the drug-polymer interface, as is perceived to occur with the crush technique. Despite certain advantages to crush and other similar approaches (such as the culotte technique), these may result in an excessive volume of metal at or near the lesion carina with an unintended susceptibility to impaired endothelialization and thrombogenicity. Moreover, using balloon alignment T-stenting, we successfully reaccessed the side branch for final post-stent dilatation in 100% of the cases, using simultaneous kissing balloon (SKA) angioplasty in 77% of the cases. That not all cases involved final kissing balloon dilation (at least at the start of the trial) is a reflection of the growing acceptance and expanding body of data of SKA as the trial progressed.¹⁰ Anatomic consequences of the crush technique merit specific comment. A recent published report² using intravascular ultrasound (IVUS) to thoroughly and systematically interrogate the entire bifurcation lesion following the crush technique confirms that the smallest minimum stent area is generally located just beyond the crush zone at the side branch ostium. This may provide a plausible explanation for previously published reports citing a 3.5% rate of subacute thrombosis and aggregate 28% restenosis rates when stenting both limbs of the bifurcation.¹ In our pilot study using balloon alignment T-stenting, the side branch binary restenosis rate was 7.4%, with 2 of the 27 side branches revascularized. Both side branches were determined by QCA to have a reference vessel diameter 11 One of these 2 restenotic side branch lesions was part of a trifurcation lesion where the LAD gave rise to 2 contiguous diagonal branches. There were no cases of in-stent restenosis of the main branch in our study. Similar to the bifurcation study published by Jeremias et al,¹² there were also no cases of subacute vessel thrombosis in the current trial, more frequent complications than reported in the earliest bifurcation studies1 and a disproportionate frequency to what has been reported in landmark DES trials.¹³ The current pilot study also confirms recent bifurcation studies⁷ which have convincingly demonstrated that MACE rates are generally driven by long-term TLR as a result of in-stent restenosis, not the acute procedural complications of fatal and nonfatal MI. There were no deaths or Q-wave MIs documented in the present study. There were 2 isolated non-Q-wave MIs. Neither of these patients suffered any serious long-term deleterious consequences as a result. In this study, a currently available DES platform was utilized in a novel fashion to address the complexities of bifurcation coronary artery disease. There have been a number of recent reports,¹⁴ both in manuscript and abstract form, detailing the results of multicenter trials using “dedicated” devices to treat this lesion subset. A comparison of our procedural success with these studies would be fraught with shortcomings, as most dedicated devices evaluated thus far do not encompass true bifurcation mechanics, but rather are merely side branch access systems. Moreover, few, if any, of these dedicated devices are drug-eluting systems. The Frontier Registry,¹⁴ one such study of a non-drug-eluting side branch access system, was associated with a 44.8% 6-month restenosis rate. Of interest, acute procedural complications in the Frontier Registry were low, with an aggregate rate of fatal and nonfatal MIs of 3 the balloon alignment T-stenting technique may provide a reasonable alternative. Use of a main branch balloon to align the stent at the side branch ostium offers a number of possible advantages: first, it facilitates ostial side branch stent deployment while largely eliminating the likelihood of protrusion of the stent proximally into the main branch, which might otherwise prevent subsequent attempts to pass devices beyond the carina in the main branch; second, it can facilitate more precise localization of the side branch stent at the ostium to avoid the commonly described problem of gaps or skipped spaces. This is demonstrated by the correlation of angiographic and IVUS images of this technique (Figure 1G). The balloon alignment T-stenting technique was associated with the remarkably low side branch restenosis rate of 7.4%. Stent shift, a phenomenon commonly described³ as occurring in the main branch on the contralateral vessel wall relative to the side branch, was of no significant clinical relevance since there were no cases of LAD in-stent restenosis. Note that in 1 patient there was a LAD main branch lesion treated with additional stenting at the 6-month anniversary angiography. This main branch lesions was not contiguous or in any way associated with the original stented bifurcation lesion, but rather represented progression of previous disease in nonstented, nonbifurcation segments of the more proximal LAD. Study limitations. The current study is limited by virtue of its small numbers and nonrandomized design. It is also a single-center feasibility experience, intentionally limiting the number of operators involved. Randomized trials against provisional T-stenting or other techniques, as well as broader operator experience, will be required to validate this technique as a viable treatment option for bifurcation coronary artery disease. It is also worth pointing out that 77% of the patients treated had Lefevre classification Type 1 lesions¹⁵ (Safian Type IA¹⁶), involving only the LAD/diagonal system. The real-world experience treating bifurcation disease encompasses a broader spectrum of lesion subtypes, therefore, this technique will need to be tested in a more diverse coronary milieu and compared to studies of similar heterogeneity.^17–19 This includes bifurcation disease in other major epicardial coronary arteries, a variety of side branch vessel angulations, as well as the harsher conditions of severely calcified disease. It will also need to be determined which, if any, of the currently available DES platforms is more ideally suited for treating this complex lesion subset as comparative studies are just beginning to emerge.^20,21Future directions. The industry race is on to be the first to develop a truly dedicated device that will optimally address the broad range of coronary anatomy and bifurcation morphology commonly encountered. It will need to be user-friendly to achieve broad appeal for operators of intermediate experience. It must also consistently demonstrate acceptable restenosis rates across a variety of lesion complexities. However, it is conceivable that as operator expertise treating bifurcation lesions grows and the “envelope is pushed” with current DES platforms, there may be more than just a theoretical concern that a dedicated device may be rendered obsolete even before it hits the catheterization laboratory shelves. Conclusion Ballon alignment T-stenting may provide a reasonable alternative to currently used techniques for the treatment of bifurcation coronary disease. In this small, single-center feasibility study, it was associated with an acceptable frequency of short- and intermediate-term MACE, including TLR. It will require further study and broader operator experience in a less select cohort to establish whether this technique will reduce the need for long-term TLR in bifurcation disease.

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