Benefits of Cutting Balloon Before Stenting

Rizik DG, Popma JP, Leon MB, et al. Benefits of cutting balloon before stenting. J Invasive Cardiol. 2003;15(11):624-628. PMID: 14608131.

Cutting balloon (CB) technology combines the features of microsurgical incision with balloon dilation to treat atherosclerotic lesions. The CB has a non-compliant dilation balloon with microsurgical blades (atherotomes) attached to the outer surface. The cutting blades serve to radially incise the atherosclerotic lesion prior to balloon expansion. Linear incisions made by the blades facilitate expansion of the atherosclerotic lesion at lower inflation pressures, resulting in less barotrauma-related injury to the vessel wall.¹ In addition, the symmetric and orderly disruption of the plaque lesion with the CB is believed to result in less injury to the vessel during expansion compared to conventional balloon angioplasty.

Clinical studies using the CB have shown promising results. Studies have demonstrated an increase in luminal gain with a corresponding reduction in restenosis rates and target vessel revascularization compared to conventional balloon angioplasty for the treatment of in-stent restenosis.^1–5 These studies have provided the rationale for using the CB as a pretreatment to stent placement in order to enhance luminal gain. Stents are widely used to expand target lesions in patients with coronary artery disease.^6–8 The use of stents has been shown to reduce restenosis rates of atherosclerotic lesions compared to conventional balloon angioplasty.^6,7 Since the minimal stent area achieved following stenting is the single most powerful predictor of long-term patency and clinical outcome,^9–12 optimization of the luminal gain is an important goal for stent deployment. Because plaque burden can limit the luminal gain, debulking lesions prior to stenting has been suggested as a strategy to further optimize luminal gain.

Several studies have shown improved luminal gain with various debulking techniques prior to stenting.^13,14 No prospective studies have been carried out to evaluate the use of CB in conjunction with stent deployment as a means to further optimize both short- and long-term outcomes. This was a non-randomized, prospective pilot study to evaluate the tolerability and feasibility of pretreating atherosclerotic lesions with CB prior to stent placement. The acute post-procedural cross-sectional area (CSA) measurements and in-hospital complications are the subject of this report.

Methods

Study design. This study was a prospective, non-randomized, open-label, multicenter trial evaluating the safety and feasibility of pretreating lesions with CB prior to coronary stent implantation. To ascertain the feasibility of the procedure, the proportion of patients with procedural successes was evaluated; to ascertain the safety of the procedure, the proportion of patients with complications was determined. In addition, the CB procedure was evaluated by measuring luminal area by angiography and intravascular ultrasound (IVUS).

Study population. Male or female patients with significant coronary artery disease requiring stent placement were eligible for enrollment in the study. Stent placement was allowed in either a de novo or restenosed (for the first time) lesion located in a native coronary artery with a reference vessel diameter between 3.0–4.0 mm. Lesions were required to have greater than 50% lumen diameter narrowing as determined by angiography and to be less than 25 mm in length. If the lesion was recurrent, restenosed, located in the left main artery or in a bypass graft, located in a stent, complicated by thrombus, severely calcified or totally occluded, the patient was not eligible to participate.

Exclusion criteria included patients with the following: myocardial infarction (MI) within the previous 48 hours; current signs of congestive heart failure; hypertension (diastolic pressure >= 115 mmHg); hypotension (systolic pressure Pre-procedure. Prior to enrollment in the study, prescreening and baseline tests were performed.

All patients received a preprocedure physical examination, including medical history, laboratory evaluations and electrocardiogram (ECG). A diagnostic angiogram was performed to document the presence of high-grade coronary artery disease. Prior to the procedure, all patients were pretreated with 325 mg aspirin for at least 24 hours.

Use of nitrates, calcium blockers and beta blockers was optional. Prior to the CB procedure, heparin was administered to achieve an activated clotting time in excess of 300 seconds. Patients were required to take aspirin 325 mg daily and clopidogrel 75 mg daily for 30 days post-procedure. Patients were also given additional heparin as needed. At the time of the procedure, coronary arteriography was performed to confirm the location of the culprit lesion. Intracoronary nitroglycerin was administered in order to measure the maximally dilated reference vessel.

Reference vessel diameter (RVD) and CSA were determined using angiography and IVUS after injection of intracoronary nitroglycerin. CB procedure. The length of the Barath^® Cutting Balloon (Interventional Technologies, San Diego, California) was determined based on the lesion length. A CB sized according to the previously determined reference diameter was selected with a targeted balloon to artery ratio of 1:1. Balloon preparation was done using a negative pressure method. A 0.014´´ wire was used to cross the culprit vessel. The CB was advanced to the culprit lesion and radio-opaque markers were positioned proximal and distal to the lesion. Once the CB was centered on the lesion, the CB was inflated to a minimum recommended inflation pressure of 4 atm (maximum of 8 atm) and maintained for at least 60 seconds.

Post-CB angiography and IVUS were performed following injection of 100–200 µg of intracoronary nitroglycerin.

Stent implantation procedure. Intracoronary stent deployment was performed to cover the entire segment pretreated with the CB. The diameter of the stent dilation balloon was sufficient to achieve a ratio of stented diameter to adjacent segment of 1.1:1. IVUS estimation of the media-to-media ratio guided the choice of stents and post-stent deployment dilation. After the stent was deployed, non-compliant dilation balloons were used to perform post-stent dilatation following a 2 atm step-up regime (10, 12, 14 and 16 atm).

The goal of further increases in dilation pressure was to achieve: 1) full stent expansion; 2) symmetry of the deployed stent; and 3) complete stent-to-lumen apposition.

IVUS procedure. A commercially available system (CVIS; Boston Scientific/Scimed, Inc., Maple Grove, Minnesota) was used for all IVUS studies. IVUS images were obtained at baseline, after each device change and with each increase in inflation pressure. All IVUS studies were performed after administration of 100–200 µg nitroglycerin, using a commercially available catheter (Boston Scientific/Cardiovascular Imaging Systems, Fremont, California). After the IVUS catheter was positioned distal to the lesion, a mechanized pullback device was used to ensure a constant rate (0.5 mm/second) of catheter movement through the lesion.

Online IVUS images were evaluated to determine the need for additional balloon inflation pressures until optimal stent deployment was achieved. Image acquisitions and analyses were performed using a standard protocol consistent with the American College of Cardiology Task Force guidelines.¹⁵ Using computerized planimetry (TapeMeasure, Indec Systems, Mountain View, California), intra-stent measurements and proximal and distal reference segment measurements were taken. CSA measurements were taken at both the proximal and distal reference segment (when available), external elastic membrane, lumen, and plaque and media (external elastic membrane area minus plaque area). CSA measurements at baseline, and with each post-stent balloon inflation, were taken throughout the stent to identify the minimum and maximum stent CSA and lumen CSA. Quantitative IVUS analyses were carried out by an independent core laboratory (G. Mintz; Cardiovascular Research Foundation, New York, New York).

Coronary angiography procedures. All cineangiograms were forwarded to a central Angiographic Core Laboratory at the Washington Hospital Center, where they were analyzed by observers who were blinded to the clinical outcomes and IVUS findings. Qualitative analyses of native vessel morphology before and after CB use were performed using standard criteria and the modified American College of Cardiology/American Heart Associated lesion complexity score.¹⁶ Quantitative angiographic analysis was performed using selected cineframes at baseline, after each IVUS run 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 (CMS-GFT, Medis, The Netherlands)¹⁶ was used to determine the average reference and minimal lumen diameters. These values were used to calculate the percent diameter stenosis (%DS) before and after interactive CB inflations, and after the procedure.

Patient follow-up. Following the procedure, routine CK-MB isoenzymes were evaluated at 8,16 and 24 hours post-procedure. ECGs were performed at 4 and 24 hours post-procedure. An independent committee reviewed all major complications that occurred during the study.

Definitions. Procedural success was defined as achievement of a residual angiographic stenosis of less than 50%. The primary efficacy endpoint for assessing luminal gain was the measurement of minimal stent CSA using quantitative IVUS. Safety evaluations included the proportion of patients with major complications while in the hospital. Major adverse cardiac events (MACE) included death, coronary artery bypass graft (CABG) surgery and non-fatal MI. Procedural complications, including the occurrence of abrupt closure, subacute closure, perforation, or flow-limiting dissection during or after the procedure, were also determined.

Statistical analysis. Descriptive statistics were performed for angiographic and IVUS parameters at each intervention. All values were expressed as means ± standard deviations. Demographics, baseline characteristics and clinical event information were summarized using descriptive statistics. Minimal stent CSAs at various pressures as measured using quantitative IVUS data were compared using two-sided, paired t-tests. Statistical significance was set at a p-value of 0.05. All statistical analyses were performed using StatView 5.0.1 (SAS Institute, Inc., Cary, North Carolina).

Results

Patient and baseline characteristics. A total of 51 patients were enrolled at 5 sites in the United States. Baseline epidemiologic descriptors and demographics are summarized in Table 1. Baseline lesion characteristics are presented in Table 2. The majority of patients represented single-vessel coronary artery disease with intact left ventricular function. Mean pre-procedure %DS was approximately 64%. There was a relatively equal distribution of major epicardial vessels represented. The majority of lesions treated were of the B1 and B2 variety.

Procedure successes. Of the 51 patients receiving the CB procedure, a total of 98% (50/51) were considered procedural successes, achieving an angiographic residual stenosis of Angiography. Use of the CB was associated with successful pre-stent reduction of the culprit lesion. The angiographic data, summarized in Table 3, show the %DS before and after CB and at final post-stent evaluation. Mean pre-procedural %DS was 64.1% ± 14.1%, mean post-CB %DS was 34.9% ± 11.0% and mean final in-stent %DS was 5.4% ± 12.2%. Increases in mean minimal lumen diameter were apparent after CB treatment and at the final in-stent evaluation compared to pre-procedural angiographic stenosis, but not at the reference vessel site.

IVUS analysis. Using the IVUS CSA analysis (Figure 1), the minimum stent CSA increased with increasing post-stent balloon dilation. The minimal stent CSA at 10 atm (8.06 mm² ± 1.53 mm²) was significantly greater (p Safety evaluation. The proportion of patients with in-hospital MACE was 7.8% (4/51), as shown in Table 4. These events included 0 deaths, three non-Q wave MIs and 1 target lesion revascularization. Of the 3 patients with non-Q wave MIs, one experienced an abrupt closure requiring further acute pharmacological intervention.

In this patient, brisk blood flow was promptly restored, with no further complications or interventions required. The other 2 patients with non-Q wave MI experienced a distal embolization requiring no further mechanical intervention. Their courses were stabilized with adjunctive pharmacological agents.

Discussion

This prospective, multicenter pilot study has shown that the CB can be used prior to stent implantation to achieve gains in minimal stent area at relatively low pressures. Significant gains in minimal stent CSA were attained with each additional inflation of 2 atm of pressure at pressures between 8 and 12 atm. No unexpected safety concerns arose using the CB prior to stent placement. The results of this pilot study suggest that significant luminal gains can be achieved using relatively low inflation pressures with CB pretreatment of the vessel prior to stent deployment.

In comparison, the CRUISE study,17 utilizing IVUS-directed conventional balloon angioplasty plus stenting, reported a minimal stent CSA of 7.78 ± 1.72 mm². This required an average inflation pressure of 18.0 ± 2.58 atm. In the current study, we were able to achieve a greater minimal stent CSA at lower inflation pressures (8.06 mm² and 8.72 mm² at 10 and 12 atm, respectively). For comparison, the CSA of the reference vessel in the current study was 7.36 ± 2.63 mm², and in the CRUISE study was 8.68 ± 2.79 mm².

The mechanism by which the combination of CB plus stenting results in greater CSA remains speculative. One potential explanation is that dilation of a vessel performed using CB causes less vessel injury than conventional balloon angioplasty. The linear incision produced by the CB results in a symmetrical and orderly expansion of the vessel wall, in contrast to the random vessel wall shearing or tearing associated with dilation using a conventional angioplasty balloon. It may also be postulated that CB pretreatment favorably alters the coronary architecture at the lesion site, allowing improved stent to vessel apposition.

The CB has shown promise in a number of studies as a potential replacement for conventional balloon angioplasty. Using IVUS measurements, Chevalier² and Muramatsu³ showed that acute luminal gain was greater with CB than with conventional balloon angioplasty. The greater luminal gain achieved with CB was associated with a lower rate of target vessel revascularizations at 9-month follow-up.² These and other studies consistently demonstrate that minimal stent CSA is an excellent marker for long-term restenosis rates.^1,5

This study was conducted in order to enhance the short- and long-term outcomes of patients undergoing stent placement by pretreating the atherosclerotic lesion with CB. We hypothesized that pretreatment of target lesions with CB prior to stent deployment would result in an increased luminal gain. The results of our study confirm work by Kinoshito,¹ who found that greater CSAs were achieved with CB using lower inflation pressures compared to conventional balloon angioplasty. The importance of the lower inflation pressures used to obtain luminal gains is underscored because of the surfeit of data, suggesting that higher inflation pressures potentially result in greater damage to the vessel wall.^18–20 The reduced barotrauma to the vessel wall may eventually lead to lower restenosis rates.

Rogers et al.²¹ used a rabbit model to elucidate the contribution of stent designs and deployment practices to vascular injury. They reported that deployment pressures between 12 and 18 atm caused exponential increases in maximum contact stress.²¹ No new or unexpected complications occurred with the use of CB prior to stent deployment. The proportion of patients with MACE in our study compares favorably to reports by previous authors using conventional balloon angioplasty as well as elective stenting studies.^22–27 Finally, there has been great enthusiasm generated over recent presentations on the initial results of drug-eluting stents.^28,29 What, if any, potentially beneficial synergy may exist between the CB and drug-eluting devices remains to be explored.

Study limitations. One limitation of this study was the lack of a randomized cohort for comparison of minimal stent CSA in a group of patients without CB pretreatment. Our results could only be compared to historical controls that reported the minimal stent CSA achieved when CB pretreatment was not used. The purpose of this study was to evaluate the tolerability and feasibility of CB prior to stent placement as a basis for conducting a larger-scale comparative study. Another limitation was that long-term outcomes were not available to be reported in this publication. Rather, we used a marker for restenosis as an indicator of the potential benefits of CB pretreatment.

Conclusion. The CB can be used prior to stent implantation to attain significant minimal stent CSAs at relatively lower pressures.

Acknowledgments.

This research was supported by Interventional Technologies in San Diego, California. The authors acknowledge Denise A. Dowler, BSN and June Helbig, RN for their help in executing this protocol.

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