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Intravascular Ultrasound Assessment of the Novel AngioSculpt®
Scoring Balloon Catheter for the Treatment of Complex Coronary
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Despite the recent advent of drug-eluting stents (DES), preparation of complex lesions (e.g., ostial, diffuse, fibrocalcified lesions and in-stent restenosis) before stent implantation remains an essential component of percutaneous coronary intervention (PCI).1,2 Inadequate stent expansion has repeatedly been associated with restenosis and acute/subacute stent thrombosis.3–7 Pretreatment with ordinary balloon catheters has not been shown to improve immediate- and long-term results of PCI.8,9 Predilatation with high-pressure balloons may also lead to significant dissection, coronary perforation, more pronounced plaque shift and substantial vessel wall damage, especially when approaching restenotic lesions, where the “watermelon seed” phenomenon has been frequently reported.10
In an attempt to modify lesion compliance and improve stent expansion, new dedicated devices for directional and rotational atherectomy, namely the Cutting™ Balloon (Boston Scientific Corp., Natick, Massachusetts) and the FX-miniRail™(Guidant Corp., Santa Clara, California) balloon catheters have been developed.11–15 The latest of these devices is the AngioSculpt® scoring balloon catheter (AngioScore, Inc., Fremont, California), which is comprised of a semicompliant balloon with a nitinol spiral cage specifically designed to address complex lesions.
The aim of this pilot study was to assess the feasibility and the safety of this novel angioplasty catheter as well as to evaluate its efficacy for the treatment of de novo and restenotic coronary lesions.
Methods
Study population. Patients in two centers (Brazil and Germany) who underwent percutaneous intervention of native coronary lesions were enrolled in this pilot study and sorted into two groups according to the type of target lesion: Group I was comprised of patients with de novo lesions, and Group II included patients with in-stent restenosis (ISR).
In Group I, the AngioSculpt catheter was used only for predilatation, followed by bare-metal stent (BMS) placement and, if deemed appropriate, postdilatation with ordinary semicompliant/ noncompliant balloon catheters. In Group II, the AngioSculpt catheter was used as standalone treatment for bare-metal ISR. A subset of patients in each group was submitted for intravascular ultrasound (IVUS). Clinical follow upat 1 and 6 months was obtained for all patients. Six-month angiographic and IVUS follow up was performed only in the ISR group.
Patients were excluded if they had an index lesion > 20 mm in length, vessel size < 2.5 mm, left main coronary disease, lesions located at the arterial or venous grafts, angulations ≥ 45 degrees, visible thrombus by angiography, a totally occluded target lesion, myocardial infarction within the last 72 hours of the revascularization procedure and serum creatine ≥ 2.0 mg/dl. Additionally, patients with proliferative restenosis (restenosis extending beyond the stent limits) were treated with additional stent placement and were therefore excluded from Group II.
Investigational device description. The AngioSculpt catheter, as previously mentioned, is a semicompliant balloon catheter incorporating a nitinol spiral cage, as illustrated in Figure 1. The nitinol spiral cage consists of three spiral wires wrapped around the balloon catheter designed to create focal concentrations of dilating force and thereby assisting in the luminal expansion of coronary lesions. When the balloon is inflated, the spiral wires slide and rotate over the balloon to achieve its fully open configuration. The expanded configuration provides a linear cutting surface that efficiently scores the plaque, allowing low-pressure dilatation and avoiding balloon slippage. Once the balloon is deflated, the spiral cage collapses to its original closed configuration. The AngioSculpt has twice the linear blade length of the FX miniRail and the 1.5 the linear blade length of the Cutting Balloon. The catheter was designed to be compatible with standard 0.014 inch coronary guidewires and 6 Fr guiding catheters. In this study, this novel device was available in diameters ranging from 2.5 to 3.5 mm and in lengths of 16, 18 and 20 mm.
As a first-in-man study, the operators were trained to increase the inflation pressure slowly (2 atm every 5 seconds) in order to achieve uniform inflation of the AngioSculpt device. Next, according to the procedure strategy, the balloon was inflated to a balloon/artery ratio of 0.8 in Group I, or a maximum 1.2 ratio in Group II. The inflation was filmed at two intervals: 1) when the device was uniformly inflated, and 2) at its maximum inflation pressure.
Study procedure and follow up. AngioSculpt balloon inflation was performed in all patients in both cohorts. Patients allocated to Group I, as mentioned previously, received a BMS right after predilatation with the investigational device. Patients in Group II underwent the final stages of the procedure after the operator deemed the AngioSculpt balloon inflation had rendered an acceptable result. When used with the sole intention of lesion preparation (predilatation), the AngioSculpt was inflated to a balloon-to-artery ratio of ~0.8. When intended to be the final step of the interventional procedure, the operators attempted to achieve a balloon-to-artery ratio of 1.2. Intracoronary stenting was performed using standard interventional techniques. Patients were premedicated with aspirin (200 mg) and were recommended to continue its use lifelong. Additionally, patients receiving a stent (Group I) were premedicated with clopidogrel (loading dose of 300 mg) initiated 24 hours before the intervention, or ticlopidine (250 mg b.i.d.) administered 72 hours prior to the percutaneous procedure, and were recommended to stay on thienopyridines for 1 month. During the procedure, heparin was administered as a bolus dose of 100 U/kg, with an additional bolus to maintain an activated clotting time > 250 seconds.
A 12-lead electrocardiogram (ECG) was obtained before the procedure, immediately afterward and 24 hours later. Blood sample laboratory analysis included creatine kinase cardiac enzymes (CK and CK-MB) before the procedure (< 24 hours) and 12–18 hours after treatment. This study was approved by the Institutional Ethics Committee, and eligible patients were asked to sign an informed consent.
Endpoints, definitions and clinical follow up. The primary objective of this study was to determine the feasibility and safety of the AngioSculpt balloon catheter during the hospitalization period. All deaths were considered to be cardiac unless a noncardiac origin could be clearly established by clinical and/or pathological study. The diagnosis of MI was based on either the development of new pathological Q-waves in ≥ 2 contiguous ECG leads and/or elevation of CK-MB isoenzyme > 3 times the upper limit of normal postprocedure during the index hospitalization, or cardiac enzyme elevation > 2 times the upper limit of normal thereafter.
Angiographic success was defined as attainment of < 20% residual stenosis by quantitative coronary angiography(QCA) in the treated segment at the end of the procedure. Procedural success was defined as angiographic success plus the absence of major adverse cardiac events (MACE) during hospitalization. As an additional analysis, we performed QCA and IVUS analysis of the presence and type of coronary dissection and acute results of the procedure, particularly in regard to acute gain and final in-stent dimensions. Clinical follow up by office appointment was obtained for all patients at 1 and 6 months. Angiographic and ultrasonographic 6- month follow up was performed only in the ISR group.
Quantitative coronary analysis. Intracoronary nitroglycerin (0.1–0.2 mg) was administered prior to and after each intervention to achieve maximal vasodilatation. QCA measurements were performed using a computer-assisted automated edge-detection algorithm (CMS-Medis, Leiden, The Netherlands). Minimum lumen diameter (MLD), reference diameter (RD) and percent diameter stenosis (%DS) were measured in two projections. Acute gain was defined as MLD after the AngioSculpt inflation minus baseline MLD. Late luminal loss was calculated as MLD after the AngioSculpt inflation minus follow-up MLD.
Quantitative IVUS analysis. IVUS was performed prior to and following AngioSculpt catheter inflation and, in Group I, was repeated after stent placement. AngioSculpt inflation was filmed in three stages: 1) when the balloon was inflated at 2 atm; 2) at full inflation; and 3) at maximum (final) pressure.
IVUS was performed after intracoronary administration of nitroglycerin (0.1–0.2 mg). The imaging catheter was advanced at least 10 mm beyond the stent/lesion. Images were acquired using a commercially available imaging system with 40 MHz transducers (Atlantis SR, Boston Scientific) featuring automated pullback at a constant speed of 0.5 mm/second. All cases were recorded on high-resolution S-VHS videotapes for subsequent analysis.
Quantitative analyses were performed according to the American College of Cardiology/American Heart Association IVUS guidelines.16 Minimal lumen cross-sectional area (MLA) in lesion segments was measured immediately pre- and post-AngioSculpt inflation and after stent implantation, and was repeated at 6-month follow up in the ISR group. Additionally, IVUS volumetric analysis was performed in the stent segment immediately pre- and post-AngioSculpt inflation and at 6-month follow up in the ISR group with commercially computer-based contour detection software (EchoPlaque, Indec Systems, Inc., Santa Clara, California) by Simpson’s rule. The following volumetric parameters were calculated for Group II: 1) stent volume; 2) vessel volume; 3) lumen volume; 4) neointimal hyperplasia (NIH) volume (stent volume minus lumen volume); and 5) plaque volume behind stent (vessel volume minus stent volume). The percentage of instent NIH volume obstruction was defined as neointimal hyperplasia volume divided by stent volume x 100. The delta (Δ) of each parameter between pre- and post-AngioSculpt inflation (Δ luminal volume, Δ NIH volume, Δ stent volume, Δ plaque behind stent and Δ vessel volume) were calculated in an attempt to understand the mechanism responsible for the acute luminalgain.
Both QCA and IVUS analyses were performed using the same in-hospital core laboratory by senior fellows under the supervision of the departments’ directors. None of the participants in this research project had any conflict of interest.
Statistical analysis. Continuous variables are expressed as mean ± standard deviation (SD). Comparisons between time intervals, procedural and follow-up measurements were performed in each patient using the two-tailed paired t-test. Categorical variables were described by counts and percentages and tested with the Fisher’s exact test. The correlation between Δ volume parameters was tested with the Pearson’s test. Probability values < 0.05 were considered statistically significant.
Results
Population data. Between October and November 2005, a total of 60 patients who matched the inclusion and exclusion criteria were consecutively enrolled in this study (Group I: n = 43, and Group II: n = 17). The mean age of the study populations were 62 ± 11.6 years (Group I) and 53 ± 9.4 years (Group II), with 26% and 18% being diabetic, respectively. In Group I, 73% of lesions were diffuse and fibrocalcified, while in Group II, 72% were considered diffuse according to Mehran’s classification.18 Baseline clinical and angiographic data are summarized in Table 1. There were no failures to cross the lesion with this new device in either group.
Procedure and clinical results. Group I. AngioSculpt full inflation was uniformly achieved at a mean pressure of 7.1 ± 3.5 atm.Final average inflation pressure was 10.7 ± 2.8 atm. All patients were successfully pretreated with the AngioSculpt catheter, and no major dissection or vessel perforation was observed. Two patients had minor dissections after AngioSculpt predilatation that were completely sealed with the stent implantation. Angiographic and procedural success were achieved in all cases. None of the patients had inhospital or 30-day MACE (death, myocardial infarction or target lesion revascularization). At 6 months, no deaths or acute myocardial infarctions were registered in this group. Five patients (10.2%) had ischemia-driven need for repeat revascularization.
Group II. For the treatment of restenotic lesions, AngioSculpt full inflation was uniformly achieved at higher pressure than for de novo lesions (10.4 ± 3.1 atm vs. 7.1 ± 3.5 atm for Group I; p = 0.02). Also, final balloon inflation pressure was higher among these patients (14.3 ± 3.1 atm vs. 10.7 ± 2.8 atm; p = 0.03). As in Group I, angiographic and procedural success were achieved in all cases. Again, no inhospital adverse cardiac event occurred among these patients. At 6-month follow up, binary restenosis (stenosis > 50%) was observed in 6 patients (35.2%). Four patients (23.5%) presented with recurrent ischemia-driven restenosis requiring additional percutaneous procedures with DES implantation.
Angiographic and IVUS results. Group I. The first 20 patients were submitted to IVUS prior to intervention, after AngioSculpt balloon inflation and immediately after stent deployment. One of them was excluded from the final analysis since the images were deemed inadequate for a reliable interpretation.
Table 2 displays QCA and IVUS data for this cohort. The average AngioSculpt balloon-to-coronary artery ratio was 0.77 ± 0.02. Between preintervention and post-AngioSculpt inflation, the minimal lumen diameter (MLD) nearly doubled from 0.89 ± 0.24 mm to 1.6 ± 0.4 mm, resulting in an acute gain of ~0.7 mm following the use of this new device.
Notably, post-Angiosculpt IVUS images were suggestive of circumferential “scoring” marks consist ent with the geometry of the nitinol spirals (Figure 2). No major dissection or vessel perforation was observed in this group. IVUS detected 2 type-A dissections after balloon inflation which were completely sealed after stent deployment. Postprocedure MLD and area significantly increased. QCA final MLD and IVUS final stent area were 2.91 ± 0.41 mm and 6.6 ± 1.0 mm2, respectively (Table 2). Final minimum area (instent) was 6.5 mm2 in 85% of the cases with de novo coronary lesions.
Group II. Balloon slippage (or “watermelon seeding” phenomenon) was not observed in this group. The AngioSculpt balloon-to-coronary artery ratio averaged 1.19 ± 0.02. QCA demonstrated an acute gain of 1.64 mm after AngioSculpt inflation, resulting in a postprocedural MLD of 2.55 ± 0.32 mm. At 6 months, late loss was of 0.54 mm (Table 3).
Final minimum area (instent) ≥ 6.5 mm2 was achieved in 82% of the cases. Serial IVUS wasattempted in all patients from Group II. However, in 3 cases, adequate images could not be obtained. Therefore, 14 individuals (82%) with a baseline and follow-up IVUS study were included in an IVUS subanalysis. QCA and volumetric analysis are listed in Tables 3 and 4. Percentage volume obstruction decreased significantly between pre- and postprocedure. There was a nonsignificant increase in stent and lumen volumes as well as in plaque and NIH volumes between postprocedure and follow-up IVUS examination. Additionally, we observed a strong linear correlation between Δ luminal volume and Δ stent volume pre- and postprocedure (Figure 3). This finding points to a better stent expansion as the main mechanism of acute gain after AngioSculpt use for the treatment of ISR.
Discussion
To the best of our knowledge, this study represents the first-in-man demonstration of safety and feasibility of this novel device for the treatment of de novo and restenotic coronary lesions. The use of the AngioSculpt balloon catheter was associated with good immediate results for both de novo and restenotic lesions. For the treatment of ISR, this device showed promising intermediate-term results.
Histologic and IVUS observations have shown that excessive plaque burden and intense plaque calcification strongly correlate with poorer stent expansion.17 IVUS studies have demonstrated a consistent association between modest final stent area (< 6.5 mm2 after BMS and < 5.0 mm2 after DES) and stent thrombosis and restenosis.4,5,18 In the present study, patients with de novo lesions pretreated with AngioSculpt achieved a final stent area of 6.6 ± 1.0 mm2. Importantly, no final minimal stent area < 5.0 mm2 was observed in either group.
A cumbersome scenario in interventional cardiology is the treatment ISR. The use of balloon angioplasty with conventional balloon catheters versus BMS for the treatment of restenotic lesions was compared in 450 patients enrolled in the RIBS trial (Restenosis Intra-stent: Balloon angioplasty versus elective Stenting).19 Patients randomized to receive another stent (n = 224) had less inhospital MACE (1.3% vs. 4.9%; p = 0.039). However, after 1 year of clinical follow up, event-free survival and binary restenosis were comparable between the groups. It is important to mention that balloon slippage during the treatment of ISR was reported in up to 12% of the cases in that trial, and i ts occurrence has been related to poorer clinical outcomes with a significant increase in restenosis recurrence when compared to those in whom the “watermelonseeding” phenomenon was not evident (56% vs. 37%; p = 0.017).10 In the present study, use of the AngioSculpt balloon catheter was not associated with balloon slippage when used for treatment of either de novo or ISR lesions.
The use of a DES might be an attractive alternative in this complex scenario. Recently, the RIBS 2 trial randomized 150 patients with BMS restenosis to either balloon angioplasty alone (n = 74) or DES implantation (n = 76).20 At the end of 1-year follow up, the primary endpoint of the study — the binary restenosis rate — was significantly reduced in the DES group (11% vs. 39%; p < 0.001). However, especially in developing countries, where economic issues may prevent the widespread use of these novel stents, AngioSculpt, costing as much as ten times less than currently- available DES, might represent a less expensive and safe alternative to treat ISR lesions, with acceptable mid-term clinical results.
Study limitations. This was not a randomized study and does not have a control arm treated with a conventional semicompliant/ noncompliant balloon catheter. The limited number of patients in each group precludes more definitive clinical conclusions. The lack of 6-month IVUS follow up in the group with de novo lesions prevents any further assessment of the long-term impact of this novel device used prior to stent implantation.
Conclusions
In this pilot study, the AngioSculpt device proved to be feasible and safe for the treatment of complex coronary lesions. Six-month results suggest that the use of this novel device is an attractive option for the percutaneous approach to treat restenotic coronary lesions and should be assessed in a larger, more complex cohort of patients.
Acknowledgement. We would like to ackowledge the important contribution of Gary Gershony, MD, in the completion of this manuscript.
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