Intravascular Ultrasound Analysis of Small-Vessel Lesions

Treated with Novel Ultra-Low Profile, Guidewire-Based Self-Expanding Stent System

ABSTRACT: Objectives. This study was performed to evaluate the long-term vascular response of the first series of patients treated by a novel ultra-low profile, guidewire-based self-expanding stent system (Sparrow™ stent) using serial intravascular ultrasound (IVUS). Background. The long-term vascular response and stent geometry change after self-expanding stent implantation are not known. Methods. The CARE 1 trial was a single-arm feasibility study of the Sparrow stent in patients with small-vessel disease. Twenty patients were included in this prospective IVUS study, and serial volumetric IVUS analysis was performed after stent implantation and at 6- and 12-months follow up. Results. Serial volumetric IVUS analysis was available in 13 cases between post-procedure and 6-month follow up and in 6 cases between 6- and 12-month follow up. At 6-month follow up, % neointimal volume was 34 ± 9%. Stent volume index was increased by 13% , negating part of the luminal loss due to neointimal hyperplasia. There was no correlation between % neointimal volume index and % change in stent volume index (p = 0.7). No additional change occurred in any IVUS parameter between 6 and 12 months after stent implantation. Conclusions. In this small feasibility study, the use of a novel guidewire-based self-expanding stent was associated with the same degree of neointimal response as that seen with conventional bare-metal stents. Through serial analyses, the IVUS parameters of both the stent and the vessel remained unchanged beyond 6 months after stent implantation. J INVASIVE CARDIOL 2008;20:647–650 Despite recent progress in coronary stents and their delivery systems, failure to deliver a stent through calcified, tortuous or stented proximal segments remains the primary cause of procedural failure.1,2 To improve stent deliverability, a better system with a smaller profile and improved flexibility is required. A novel stent and delivery system known as the Sparrow™ (CardioMind, Inc., Sunnyvale, California) consists of a bare-metal, self-expanding nitinol stent incorporated into an assembly miniaturized to a 0.014 inch diameter guidewire platform. Through this novel design, the crossing profile of this platform is equivalent to conventional guidewire dimensions, thereby offering excellent flexibility that facilitates stent delivery to those lesions currently inaccessible with present-day stent delivery systems. While the short-term vascular response to a self-expanding stent has been reported in previous studies,3–5 follow up beyond 6 months in terms of changes in stent geometry as well as vascular response is not known. Thus, this study was performed to evaluate the 6- and 12-month vascular response of the first series of patients treated with this novel stent system using serial intravascular ultrasound (IVUS) analyses. Materials and Methods Study population. Between March 2006 and January 2007, 22 patients were enrolled in a two-center, single-arm feasibility study of the Sparrow stent (CARE 1 trial). Inclusion criteria were single de novo coronary artery lesions with a reference vessel diameter between 2.0–2.5 mm and lesion length ≤ 14 mm. Once the consent forms were signed, 20 patients were included in this prospective serial IVUS follow-up study (6 and 12 months). Procedure. Coronary stenting was performed using standard interventional techniques. Through the use of a conformable radiopaque guidewire tip at its distal end, this stent system was able to be delivered to the target lesion after balloon angioplasty, at which time the stent was detached from the system. Following stent deployment, the delivery system can then be used as a guidewire for additional procedures. Adjunctive balloon dilatation after stent implantation was performed in all cases. A detailed description of this system and stent deployment procedure was provided in a previous case report.6 Aspirin was given indefinitely and clopidogrel was maintained at least for 3 months after the procedure. IVUS procedure and analysis. For all cases, serial IVUS analyses were planned post procedure, at 6 months and 12 months after stent implantation. The IVUS procedure was performed in a standard fashion using an automated motorized pullback system (0.5 mm/sec) with commercially available imaging systems. IVUS analysis was done in an independent core laboratory at Stanford University Medical Center (Cardiovascular Core Analysis Laboratory, Stanford, California) blinded to the clinical and angiographic information. Quantitative analyses were performed using computerized planimetry software (echoPlaque, Indec Systems Inc, Santa Clara, California) as previously described.7 Serial two-dimensional and volumetric IVUS analyses were performed for both the stent and persistent (5 mm distal and proximal to the stent edge) reference segments. Measurements of the vessel (external elastic membrane), stent and lumen areas were made at 1 mm axial intervals and volumes were calculated using Simpson’s rule. To adjust for the difference in length of measured segments, the parameter of volume index was derived from each volume parameter using the formula of volume/measured length (mm3/mm). Percent neointimal volume was defined as neointimal volume divided by stent volume. Incomplete stent apposition (ISA) was defined as one or more struts separated from the vessel wall with evidence of blood speckles behind the strut(s). ISA was classified as persistent, resolved, or late-acquired as previously described.8 Statistical analysis. Data are presented as mean ± standard deviation for continuous variables and as frequency for categorical variables. Comparisons of continuous variables were performed using the student’s or paired t-test. Categorical data were compared by the 2 test or Fisher’s exact test. IVUS parameters between 6 and 12 months after stent implantation were compared by a Wilcoxon Signed Ranks test. Pearson’s correlation analysis was used to evaluate the correlations between IVUS parameters. All tests were two-sided and a p-value Results Follow-up IVUS was performed in 16 cases at 6 months and 8 cases at 12 months after stent implantation. After exclusion of cases with inadequate image quality, serial volumetric analyses were available in 13 cases between post procedure and 6-month follow up, and in 6 cases between 6- and 12-month follow up. Baseline characteristics of the patients are shown in Table 1. There were no differences in baseline clinical and angiographic characteristics between patients with and without available serial volumetric IVUS analysis at 6-month follow up. Qualitative IVUS analysis. Postprocedural ISA was found in 6 patients (30%), and there was no late-acquired ISA. Four cases of ISA were tiny-edge ISA involving only 1 stent strut. The other 2 were due to size mismatch between vessel and stent. Six-month quantitative IVUS analysis. Six-month follow-up volumetric analysis was available in 15 patients, and serial volumetric analysis was available in 13 patients. At 6-month follow up, the neointimal volume index was 1.45 ± 0.46 mm3/mm and the percent (%) neointimal volume was 34 ± 9% (n = 15). Stent volume index was increased by 13% during follow up, negating luminal loss due to neointimal hyperplasia by 33% (Table 3). Despite stent expansion, there was no change in vessel volume index during follow up (8.4 ± 1.7 mm3/mm at baseline, 8.4 ± 1.7 mm3/mm at follow up; p = 0.69). No correlation was found between % neointimal volume index and % change in stent volume index (p = 0.7). However, % change in stent volume index had a positive correlation with % change in lumen volume index (r = 0.7, p = 0.01) (Figure 1). There were no significant changes in IVUS parameters of reference segments except for the increase in plaque volume index at the distal reference segment (2.8 ± 1.4 to 3.1 ± 1.5 mm3/mm; p = 0.04). This slight change did not cause luminal narrowing in that segment. When IVUS parameters in stent segments were compared with those of a previous-generation self-expanding coronary stent (Radius Stent, Boston Scientific Corp., Natick, Massachusetts) data from ASSURE trial,4 (n = 22), the Sparrow stent showed less degree of stent expansion during 6-month follow up (13.4 ± 11.1 vs. 25.9 ± 15.0%; p = 0.01). However, there was no difference in % neointimal volume (31.9 ± 8.2 vs. 33.7 ± 19.7%; p = 0.72) or % change in luminal volume index (-22.6 ± 13.7 vs. -16.2 ± 26.9%; p = 0.36) (Figure 2). Twelve-month quantitative IVUS analysis. Serial volumetric IVUS analysis between 6 and 12 months was available in 6 patients. There were no additional changes in any IVUS parameter between 6 and 12 months after stent implantation in either stent or reference segments (Table 4). Discussion This is the first report of a 1-year IVUS analysis of small-vessel lesions treated with the novel ultra-low profile, guidewire-based self-expanding stent system. The major findings of this IVUS analysis were: 1) this stent expanded by 13% during 6-month follow up, and the amount of neointimal hyperplasia was comparable to that of conventional bare-metal stents; 2) stent expansion negated luminal narrowing mostly by plaque compression and not by vessel stretching; and 3) there was no additional change in vessel or stent parameters beyond 6 months after stent implantation. In small-vessel disease, stent implantation results in better clinical outcomes, especially when angioplasty is suboptimal.9 However, the clinical benefit of stent implantation cannot be achieved in some very tortuous or calcified distal lesions due to limited deliverability of current stent system.2 This may be one of the main reasons of low procedural success rate in small vessel disease.1,2,10 Considering the ultra-low profile and much improved flexibility, this novel stent system will provide much improved deliverability in such complex lesions. In this study, % neointimal volume of this stent at 6 months after stent implantation was 34%. This value is comparable to general bare-metal stents11 or a previous-generation self-expanding stent.4,5 This stent expanded by about 13% and it was less than that of a previous-generation self-expanding stent. Less expansion of the Sparrow stent seems to be due to the difference in stent diameter, stent structure and strut thickness. It is interesting to note that the vessel size did not change during follow up, despite the expansion of the Sparrow stent. Luminal gain by stent expansion was achieved mostly by plaque compression and not by vessel stretching. Previous animal studies revealed that vessel expansion by nitinol stents caused an exaggerated matrix-rich neointimal formation.12,13 In our study, there was no correlation between the degrees of stent expansion and neointimal formation. Although the optimal degree of stent expansion is not known, this study’s results suggest that there could be some threshold below which stent expansion does not cause vessel stretching. The long-term vascular response to a self-expanding stent beyond 6 months after stent implantation has not been studied yet. Theoretically, remodeling of the matrix-rich neointima can result in luminal gain during long-term follow up,14 but prolonged injury due to chronic stent expansion may cause delayed luminal narrowing. Serial volumetric IVUS analyses in this study revealed that there were no additional changes in either the stent or the vessel between 6 and 12 months after stent implantation. This result suggests that the nature of this self-expanding stent became like that of bare-metal stent beyond 6 months after implantation.15 Small-vessel intervention is becoming more frequent16 and drug-eluting stents have shown efficacy in this complex lesion subset as well.17 However, current-generation stents do not have a platform dedicated to small vessels, thus deliverability can be an issue in treating severely complex lesions.2 The drug-eluting version of this stent system has already been developed and is under clinical evaluation. If successful, this breakthrough technology will definitely widen the field of percutaneous coronary intervention. Study limitations. The main limitations of this study were that this was not a randomized study and included only a small number of patients. In addition, serial volumetric IVUS analysis was available in only a limited number of patients. Conclusion In conclusion, use of a novel guidewire-based self-expanding stent in a small-vessel subset was associated with the same amount of neointimal response as conventional bare-metal stents. Assessment of serial IVUS parameters of both the stent and vessel revealed no changes beyond 6 months after stent implantation.

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