Determination of the Minimum Inflation Time Necessary for Total Stent Expansion and Apposition: An In Vitro Study

ABSTRACT: Objective. Determine minimum inflation time necessary for total stent expansion and apposition. Background. Complete stent expansion is needed to adequately support the increase in artery lumen and to accommodate neointimal growth. Methods. Experimental in vitro study. Twenty-five silicon carbide-coated stainless steel stents (3.5 x 20 mm) were released (14 atm) in plastic vials with a 3.5 mm internal diameter. Five groups, with 5 stents each, were set. Stents from Group A were released with 5 seconds of inflation; stents from Group B, with 15 seconds; stents from Group C, with 30 seconds; stents from Group D, with 60 seconds; and stents from Group E, with 90 seconds. Immediately after release, an intrastent ultrasound evaluation was performed for analysis of intrastent volume and apposition. Data were analyzed by Tukey’s test and Fisher’s exact test. Results. Group A, mean intrastent volume (MIV) was 161.1 ± 7.5 mm3, 60% complete apposition; Group B, MIV was 180.2 ± 6.0 mm3, and 80% complete apposition; Group C, MIV was 183.0 ± 1.1 mm3, 100% complete apposition; Group D, MIV was 183.2 ± 1.8 mm3 and 100% complete apposition; and Group E, MIV was 183.5 ± 0.7 mm3, and 100% complete apposition. MIV was significantly different only in Group A, as compared to all other groups, and only stents in Groups A and B were nonapposed. The exponential curve of the relationship between inflation time/volume obtained showed maximum efficiency starting at 30 seconds. Conclusion. The experimental models used in this study showed that 15 seconds may be adequate, but 30 seconds and more appear very adequate for optimum stent deployment, expansion and apposition.

J INVASIVE CARDIOL 2008;20:396–398

 Coronary stents are used to improve the results of percutaneous coronary interventions1 and represent a mechanical solution for a biological problem.2 Complete expansion of the stent is needed to adequately support the increase in artery lumen and to accommodate possible neointimal growth. The intrinsic thrombogenic nature of stents has been questioned for a long time3 and incomplete expansion or apposition emerged as possible causes for worse outcomes.4,5 Later studies6,7 showed that stent implantation at high pressures, preferably with postdilatation noncompliant balloons, without mandatory ultrasound guidance, but with adequate dual antiplatelet therapy treatment and compliance, resulted in low rates of thrombosis. Those aspects seem to be much more relevant at present, where important safety concerns emerged with the widespread use of drug-eluting stents.8,9 The minimum or ideal time needed for complete expansion and apposition of the stent struts has not been investigated in detail yet. The duration of balloon inflation during stent deployment is at the operator’s discretion and is based on previous self-experience or on manufacturers’ recommendations. Although studies3–6 have investigated the adequate pressure level for stent deployment, the inflation time has not been systematically studied. The literature describes inflation times ranging from 15 to 90 seconds,10–13 but none of these studies justified these choices. It may have a significant impact on the elastic and plastic proprieties of the stent, regardless of manufacturing type, design and deployed pressure.14 The present study aimed to determine the minimum time of balloon inflation for complete stent expansion and apposition in an experimental model.

Methods: In this experimental in vitro laboratory study, data collection was entirely randomized. Twenty-five rapid-exchange silicon carbide coated stainless steel stents, with 3.5 mm diameter and 20 mm length, were used. The described manufacturing nominal pressure of each stent was 10 atmospheres (atm). Five groups, with 5 stents each, were set. Stents from Group A were released with 5 seconds of inflation; stents from Group B, with 15 seconds; stents from Group C, with 30 seconds; stents from Group D, with 60 seconds (as recommended by the manufacturer), and stents from Group E, with 90 seconds. The sequence of deployment time was randomly set, and release pressure was 14 atm. The stents were released in plastic vials with a 3.5 mm internal diameter and 50 mm length. The combination stent/test vial was immersed in physiological solution in a thermostatically controlled water bath at a constant temperature of 37°C to simulate body temperature. The solution used in the inflation device was composed of 10 ml of physiological solution and 10 ml of ionic contrast medium, the same as employed in regular procedures. The device in which the experiments were performed was specially designed for this study (Figure 1). The guidewire (0.014 mm x 175 cm) was positioned through the conducting tubing and the test vial where the stent was released, and the combination balloon/stent was placed by direct visualization in the center of the vial. The inflation device, containing 10 ml of the 50% iodate contrast solution, was connected to the balloon catheter and was depressurized; next, pressure was applied at 2 atm/second until a pressure of 14 atm was reached. After maintaining this pressure during the established period of time, the inflation device was depressurized. Deflation of the balloon was visually monitored and after completion, the balloon was removed. The ultrasound catheter was then inserted and images acquired. This sequence of steps is presented in Figure 2. Several parameters were investigated. The cross-sectional area (continuous variable, expressed in square millimeters) was evaluated by quantitative offline measurement and automatically determined by the ultrasound device after defining the stent margins (each stent was measured twenty times, one for each millimeter). The intrastent volume (continuous variable, expressed in cubic millimeters) was calculated using Simpson’s rule,15 based on the twenty measurements of the cross-sectional area, which was considered as one millimeter wide. The dilation rate (continuous variable, expressed as percentage) was determined by the relationship between the observed intrastent volume and the expected volume (192.4 mm3 according to Simpson’s rule). Apposition of the struts of the stent (categorical variable, dichotomized into “yes” or “no”), indicating complete apposition of the struts to the internal wall of the plastic vial, was evaluated by ultrasound. The criteria for optimal expansion of the stents included at least 90% of expected volume and complete apposition. Continuous variables are presented as mean and standard deviation and were compared by variance analysis followed by Tukey’s multiple comparison test. Categorical variables are presented as percentage and were analyzed by Fisher’s exact test. A value of p < 0.05 was considered statistically significant. Curve Expert 1.3 software was used for analysis of the relationship between duration of balloon inflation and intrastent volume, and Sanest software was used for statistical analysis.

Results: The results are presented in Table 1. The smallest mean cross-sectional area and intrastent volume were observed in Group A, indicating a smaller dilation percentage than expected. This group also presented the smallest apposition percentage. In Group B, the mean intrastent volume and cross-sectional area were higher than in Group A, but smaller than in Group C. Statistically significant differences, however, were only observed when the mean final volume and the expected/observed volume relationship were compared with Group A results. Only 1 case of nonapposition was observed in Group B, whereas in Group C, all stents showed complete apposition. Although showing no significant differences when compared to Group B stents, in Group C, the curve expressing the relationship between duration of inflation and volume begins to plateau (Figure 3). Figure 3 shows the exponential relationship between the duration of balloon inflation and intrastent volume in the 5 experimental groups, with a correlation coefficient of 0.91 and a standard deviation of 4.20. The representative equation for the curve is: y = a(b-e-cx), where a = 59.5045; b = 3.0801 and c = 0.1970. It is important to observe that maximum efficiency was achieved when the balloon was inflated for 30 seconds (Figure 3).

Discussion: Final intrastent volumes observed in this study demonstrate that short inflation periods of 5 seconds are not sufficient for complete expansion of the stents. All other experimental conditions tested (15, 30, 60 and 90 seconds) resulted in adequate stent expansion, with no significant differences among the groups. A transition zone was observed between 15- and 30-second groups, where a tendency of the curve shows that maximal efficiency is obtained with 30 seconds. A volume of 183.11 mm3 was obtained in this group, and, after that, differences were too small, showing that no significant improvement is obtained with an increase in balloon inflation time. Perhaps it was due to the low sample size, namely 5 per arm, that the 15- second group had only 1 unapposed stent. It is possible, therefore, that a repeat of this protocol may find that the 15-second group is equally efficacious as the longer inflation time groups. It is necessary to point out that our findings may be applicable only for the tested stent and that our model may not accurately predict optimal duration of inflation time for other types of stents, including drug- and polymer-coated stents, which may require shorter or longer inflation times for optimal expansion. Despite these concerns, the findings of this small study lead us to reflect on an interesting mechanistic hypothesis for this issue. It is well known that the lack of apposition of the struts to the vessel walls induces flow disturbances resulting in increased tension and shear stress. It can represent potential mechanical stimuli for restenosis16 and enhance rheologic disturbances that can lead to clot formation, determining acute, subacute, late or very late stent thrombosis.17 In particular, the latter are extremely important and could have potential clinical implications due to the safety issues regarding the use of drug-eluting stents. This study does not consider the influence of external forces represented by plaque and vessel wall pressure against the stent. Due to the great variability of plaque morphology and composition18 and to the modifications induced by the stent in the artery walls after its deployment, no histomechanical models adequately represent arterial diseases.19,20 Complete dilation was not observed in any of the experimental groups. According to in vitro and in vivo angiographic and ultrasound correlations,21 this might be explained by the fact that, due to the hard composition of the plastic vials used, the stent is placed over its surface, and even when completely expanded, has a luminal diameter slightly smaller than that of the model. The plastic model also does not simulate vessel recoil, nor does it allow tissue accommodation, as seen in coronary arteries and high-pressure stent delivery, as was used in this experiment. Also, in certain clinical scenarios, it could potentially lead to perforation or frank rupture, and thus represents the main limitations of the present study. Although in an in vivo study, Takano22 observed that even with relatively high pressures (14 to 16 atm), the cross-sectional area of the stents was, on average, only 62% of what was expected. Furthermore, complete expansion and apposition of the stents cannot be confirmed by angiography. Considering that many centers do not routinely perform intracoronary ultrasound, and that we still do not have enough information in this particular field, results of the present experimental study can provide new insights for an adequate stent implantation technique. In conclusion, the experimental models used in this study showed that 15 seconds may be adequate, but 30 seconds and higher appear very adequate for optimum stent deployment, expansion and apposition.