The Impact of Cutting Balloon Angioplasty for the Treatment of Diffuse In-Stent Restenosis

Iijima R, Ikari Y, Anzai H, et al. The impact of cutting balloon angioplasty for the treatment of diffuse in-stent restenosis. J Invasive Cardiol. 2003;15(8):427-431. PMID: 12890868.

Since evolutional trials demonstrated the superiority of stent implantation over balloon angioplasty for the reduction of restenosis,^1,2 the indications for stent implantation have been expanded and now include a variety of coronary arterial lesions. However, restenosis following stent implantation occurs in approximately in 20–30% of cases. Balloon angioplasty has been widely used with a high initial success rate. However, long-term results have been disappointing due to the high recurrence rate of in-stent restenosis (ISR).^3–7 Therefore, developing an effective strategy to treat ISR is an important clinical problem in the field of interventional cardiology.

Mehran et al.⁸ presented a new angiographic classification of ISR, which has been shown to predict the late outcome after treatment of ISR. Previous reports^9–12 have shown that diffuse ISR is associated with a high recurrence rate compared with focal ISR; it has been reported that the recurrence rates following balloon angioplasty for diffuse ISR are as high as 80%.³ Therefore, great attention has been focused on the development of new treatments for diffuse ISR. Adamian et al. recently reported that cutting balloon angioplasty (CBA: Interventional Technologies Inc., Calif.) is an alternative strategy for the treatment of ISR that has a high success rate (100%) and low incidence (20%) of angiographic restenosis at follow-up.^13–15 This study attempted to reproduce those results, focusing on diffuse ISR.

Methods

Patient population. Between January 1994 and November 2000, a total of 1,290 patients were treated with intracoronary stenting at our institution. Of this cohort, 260 patients with 277 lesions desired treatment for cardiac ischemia secondary to ISR. One hundred and seventy lesions were excluded from this study for the following reasons: 1) the lesion was focal ISR (n = 118); 2) percutaneous coronary intervention (PCI) for ISR had been repeated more than twice (n = 32); 3) angiographic follow-up was not obtained (n = 13); 4) the procedure was unsuccessful (n = 2); and 5) diffuse ISR was treated by rotational atherectomy or stent-within-stent implantation (n = 5). Thus, data from the remaining 107 lesions in 104 patients (75 men; mean age, 64 ± 10 years; age range, 41–82 years) treated by balloon angioplasty (BA) or CBA were analyzed in this study.

The BA group consisted of 46 lesions and the CBA group consisted of 61 lesions. The majority of stents that developed restenosis were slotted-tube stents (n = 94; 88%). Stent size was 2.5 mm in 4 cases, 3.0 mm in 62 cases, 3.5 mm in 32 cases, and 4.0 mm in 9 cases. Angiographic follow-up was conducted routinely at 6 months, and the prevalence of restenosis was determined.

Procedures. All patients received aspirin 81–162 mg orally throughout the follow-up period. A bolus of 100 IU/kg of heparin was administered after insertion of the sheath and titrated to maintain an activated clotting time > 250 seconds throughout the procedure. Abciximab was not given to any patient. The device to treat ISR was selected at operator discretion. Initially, the same size balloon as the implanted stent was used in both groups. However, four lesions in the CBA group were predilated using conventional balloon catheters with a diameter of 1.5 mm or 2.0 mm, because the stents were totally occluded. BA for ISR was performed using standard techniques with semicompliant balloons at an inflation pressure of 15 ± 4 atmospheres, and a balloon/artery ratio of 1.19 ± 0.24. The CB is a conventional balloon catheter, 10 or 15 mm in length, that has 3 or 4 blades mounted longitudinally on the surface of the balloon. The CBs in this study had a length of 15 mm (67%) or 10 mm (33%). If the proximal area of the target lesion had a tortuous lesion, we selected the CB with a length of 10 mm. When residual stenosis was present, a balloon with a diameter up to 0.25 mm greater than the width of the lesion was used (n = 10 cases). Multiple inflations (8 ± 4 inflations) were performed, with a balloon/artery ratio of 1.27 ± 0.22 at a mean inflation pressure of 8 ± 2 atmospheres (atm) in the CBA group. Intravascular ultrasound (IVUS) was routinely used in both groups whenever possible. The procedure was IVUS-guided in 27 lesions (59%) in the BA group and in 42 lesions (69%) in the CBA group (p = 0.31).

Definitions. A diffuse ISR was defined as a lesion > 10 mm in length. Diffuse ISR were divided into three types: 1) intrastent type, i.e., within the stent proper; 2) proliferative type, i.e., lesion length > 10 mm and extending beyond the stent margins; and 3) total occlusion type, i.e., a lesion with TIMI flow grade 0. Procedural success was defined as residual stenosis 50% diameter stenosis by QCA.

Angiographic analysis. Coronary angiography was carried out in a routine manner. QCA was performed using the automated edge detection system CMS (Medis Medical Imaging Systems, Leiden, The Netherlands) by experienced interventional cardiologists. Reference diameter, minimum lumen diameter (MLD) and percent diameter stenosis (%DS) before intervention, after intervention and at follow-up were measured using a single matched worst view. Lesion length was measured on the baseline angiogram as the distance from the proximal to distal lesion shoulder in the projection with the least amount of foreshortening.¹⁶ Acute gain, late loss, loss index and net gain were also calculated. Acute gain was defined as MLD after treatment minus MLD at follow-up. Late loss was defined as MLD after treatment minus MLD at follow-up. Loss index was calculated as the ratio between the late loss and the acute gain. Net gain was calculated as acute gain minus late loss. Angiographic restenosis was defined as %DS > 50% by QCA on follow-up angiography.

IVUS analysis. The IVUS studies were performed using a 2.9 French IVUS catheter with a 30 MHz transducer (Cardiovascular Imaging Systems, Boston Scientific/Scimed, Inc., Maple Grove, Minnesota). IVUS was performed before and after treatment. The imaging catheter was advanced more than 10 mm distal to the lesion, and the transducer was withdrawn mechanically at a speed of 0.5 mm/second.¹⁷ All images were recorded on high-resolution, super VHS videotape for offline analysis. IVUS images were analyzed by 2 experienced individuals using a computer-assisted offline analysis system (TapeMeasure, Indec Systems, Capitola, California). The cross-sectional area (CSA) was manually traced. The stent, vessel and lumen CSAs pre- and post-procedure were measured at 5 points (proximal and distal reference segment, stent proximal and distal edge segments and the point of the narrowest lumen CSA inside the stent in the diastolic frames). The proximal and distal reference segments were selected in the segments closest to the lesion that were most normal appearing. When the plaque enveloped the catheter, the lumen was assumed to be the same physical size as the imaging catheter. Quantitative IVUS images were analyzed by 2 observers on 2 separate occasions. The intraobserver correlation coefficients for vessel CSA and lumen CSA were 0.989 and 0.993, respectively, and the interobserver correlation coefficients for vessel CSA and lumen CSA were 0.998 and 0.995, respectively.

Statistics analysis. Statistical analysis was performed using StatView 5.0 software (SAS Institute, Cary, North Carolina). Data are expressed as means ± 1 standard deviation. Categorical variables between groups were compared with the Chi-square test and Fisher’s exact test. Continuous variables were compared using Student’s unpaired t-test, the Mann-Whitney U-test, and repeated measure ANOVA. Statistical significance was accepted when p was Demographic and clinical characteristics. Age, gender, risk factors and history of previous myocardial infarction and coronary artery bypass surgery were similar between the 2 groups. Diabetes was common in both groups (50% for CBA group versus 59% for BA group; p = 0.43) (Table 1). The right coronary artery was treated more frequently by BA (59%) than CBA (28%; p = 0.02). The angiographic ISR patterns were similar. Total occlusions were present in 11% of patients in the CBA group and in 24% in the BA group, and a proliferative pattern occurred in 28% of the CBA group and in 28% of the BA group. Procedural characteristics were similar, except the maximal inflation pressure was greater in the BA group than in the CBA group (15 ± 4 atm versus 8 ± 2 atm, respectively; p = 0.01) (Table 2).

Procedural success and complications. Dilatation was unsuccessful in 2 patients with totally occluded ISR (1 in the BA group, 1 in the CBA group). No major complications occurred during hospitalization. Thus, the procedural success rate was 99% in both groups. The unsuccessful cases were excluded from further analyses.

IVUS results. IVUS measurements before and after the procedure were similar in the 2 groups (Table 3). IVUS demonstrated that the stent CSAs in both groups were not different before the procedure. In the CBA group, seventy-six percent of the lumen gain was attributed to compression and/or extrusion of neointima and 24% was attributed to stent expansion. In the BA group, seventy-two percent of the gain was attributed to compression and/or extrusion and 28% was attributed to stent expansion (p = NS).

Angiographic outcomes. QCA measurements in the BA and CBA groups were similar before the procedures (Table 4). The ISR lesions longer than 20 mm were 23.0 ± 14.1 mm in the BA group and 22.6 ± 14.2 mm in the CBA group. The MLDs and mean diameters of the reference vessel before and after the procedure and at follow-up were similar in the 2 groups. The differences in acute gain, late loss, loss index and net gain between the 2 groups did not reach statistical significance. On the other hand, the post-procedure %DS was lower in the CBA group than in the BA group (19 ± 12% versus 27 ± 12%, respectively; p = 0.001). %DS at follow-up was lower in the CBA group than the BA group. Consequently, the angiographic restenosis rate tended to be lower in the CBA group than the BA group (34.4% versus 52.2%, respectively; p = 0.08) (Figure 1). Lesion length decreased from 26.2 ± 14.3 mm to 15.9 ± 7.3 mm in the CBA group, while the lesion length in the BA group did not change in length (p = 0.02) (Figure 2). Incidence of diffuse ISR pattern following CBA was lower than following BA (20% vs. 48%, respectively; p = 0.01) (Figure 3).

Comparison of restenosis rate after the same procedure of a second ISR. A total of 30 lesions complicated 30 recurrent ISR (14 lesions in the BA group and 16 lesions in the CBA group). For the recurrent ISR, the same procedure was performed. The incidence of second angiographic restenosis was lower in the CBA group than in the BA group (37.5% versus 78.6%, respectively; p = 0.03) (Figure 1). Discussion The present study showed: 1) the initial success rate of CBA for diffuse ISR was satisfactory; 2) lesion length following CBA was shorter in the recurrent ISR; and 3) angiographic ISR pattern of recurrent ISR was favorable following CBA.

Comparison with other strategies for diffuse ISR. The recurrence rate after treatment for ISR varies among different series of studies because of different endpoints (angiographic recurrence or target lesion revascularization) and of different target lesions (focal ISR or diffuse ISR). Diffuse ISR has been shown to be associated with a higher revascularization rate. Strategies for ISR, especially diffuse ISR, are evolving. BA has been the most commonly used procedure. However, the recurrence rate ranges from 42–85%. These data are consistent with the recurrence rate of 52.2% in the BA group in this study. Another treatment option is debulking with rotational atherectomy,^18–22 laser ablation^23–25 or directional atherectomy.²⁶ The restenosis rate following rotational atherectomy was reported to be 49% in Germany. Sharma et al.¹⁸ found a target vessel revascularization rate of 32% with respect to diffuse ISR. The ARTIST study²² confirmed the lack of any advantage of rotational atherectomy and adjunctive balloon angioplasty for binary restenosis; the target lesion revascularization rates were 64.7% and 47.8%, respectively. Implantation of a new stent for ISR has also generated disappointing results.^27,28 Recently, the results of brachytherapy using gamma and beta radiation for the treatment of diffuse ISR have been reported.^29–31 The rate of angiographic restenosis at 6 months in the GAMMA-1 trial was 32.4%. The independent predictors of restenosis were a longer lesion, and a lesion in the left anterior descending coronary artery. The INHIBIT and START trials, using beta radiation, also showed a reduction in the recurrence of restenosis after stent implantation. In our study, the restenosis rate of CBA for diffuse ISR was 34.4%. CBA seems the most logical approach to prepare the diffuse or proliferative ISR for a more definite therapy such as brachytherapy.

CBA for in-stent restenosis. The advantage of the CB, which has longitudinal microblades, is its ability to control disruption of the atherosclerotic plaque and neointimal tissue. Subsequently, it dilates the target vessel with less force to decrease the risk of neoproliferative response. The Japanese Multicenter Registry of CBA for ISR reported data on 194 lesions treated with CBA. Angiographic restenosis occurred in 29% and target lesion revascularization was required for 22% of lesions.³² Adamian et al.¹⁵ also reported that CBA is a viable alternative strategy for the treatment of ISR, with an excellent clinical success rate (100%) and low incidence of angiographic restenosis at follow-up (20%). In their study, the late loss was lower in the CBA group (0.63 ± 0.6 mm) than the BA group (1.07 ± 0.8 mm). Although our overall initial success rate was 99%, the angiographic restenosis rate following CBA was 34.4%, and differences in late loss between CBA and BA did not reach statistical significance (0.81 ± 0.58 mm versus 0.87 ± 0.79 mm, respectively; p = 0.63). The discordance between the results of the previous report and our study can be explained by different target lesions reported in that study; in addition, only 35.1% of the lesions were diffuse type, and the percentage of patients with diabetes mellitus was low (14%). Our data showed that CBA has a shortening effect on lesions of ISR. However, IVUS studies revealed no difference between CBA and BA. The mechanism is currently unknown. Recently, histological examination of neointima in ISR has shown that it consists of mainly extracellular matrix with a small number of vascular smooth muscle cells.33 Balloon dilatation with cutting might cause less injury than simple dilatation. However, dilatation is the main mechanism of gaining lumen area in both CBA and BA. This may be the reason IVUS data were similar in both groups.

Study limitations. This study is a retrospective analysis of a relatively small study population, albeit with 100% follow-up angiography. Volumetric analysis using IVUS was not performed.

Conclusion. This study showed that CBA is a safe and effective strategy that achieves relatively favorable long-term results. Moreover, CBA produces a shorter lesion even when ISR recurs, and the recurrence is less likely to be the diffuse type. Prospective randomized trials are needed to establish the benefits of CBA for diffuse ISR.

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