Comparison of Acute Vessel Wall Injury After Self-Expanding Stent and Conventional Balloon-Expandable (FULL TITLE BELOW)

FULL TITLE: Comparison of Acute Vessel Wall Injury After Self-Expanding Stent and Conventional Balloon-Expandable Stent Implantation: A Study with Optical Coherence Tomography

ABSTRACT: Background. The acute impact in vivo from a self-expanding stent on the vessel wall has not been sufficiently evaluated. Objectives. We sought to compare acute in vivo injury on the vessel wall and the clinical impact between a self-expanding coronary stent and conventional balloon-expandable stents immediately after stent implantation. Methods. We included 40 patients (45 vessels) with stable or unstable angina who were assigned to either the self-expanding stent (vProtect® Luminal Shield) group (n = 9; Group 1) or the conventional balloon-expandable stent group (n = 36; Group 2). Optical coherence tomography (OCT) was performed after stent deployment, as were qualitative and quantitative assessments of tissue prolapse, intrastent dissection, edge dissection and incomplete stent apposition. Results. Tissue prolapse was visible in all vessels in both groups. The corrected tissue prolapse area by stent length was larger in Group 2 than in Group 1 (0.06 ± 0.06 vs. 0.02 ± 0.01 mm²; p

J INVASIVE CARDIOL 2010;22:435–439

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Although balloon-expandable stenting techniques with high pressure have proved to be useful for optimal stent implantation to reduce the risks of restenosis and subacute thrombosis, this stent deployment strategy may also increase the risk of creating vessel damage in the stented segment or at its edges.¹ As a stent is expanded with high pressure, immediate injury occurs deep in the vessel wall within the stented segment as well as in the unscaffolded persistent margins.² Importantly, several stent trials have drawn our attention to the problem of accelerated lumen loss at stent margins, which accounts for up to one-third of target-vessel revascularization (TVR) in patients treated with balloon-expandable stents.^3–5 On the other hand, a self-expanding stent allows deployment at lower pressures, resulting in less intimal trauma. Late loss was significantly smaller at the persistent margins in the self-expanding stent than it was in the balloon-expandable stent.² Optical coherence tomography (OCT) is a high-resolution technique that allows very detailed assessment of the relationship between the stent and the vessel wall. The objective of the present study was to qualitatively and quantitatively compare with OCT the stent implantation-associated vessel wall injury between a self-expanding stent (vProtect® Luminal Shield, Prescient Medical, Inc., Doylestown, Pennsylvania) and conventional balloon-expandable stents, and to compare their clinical impact during the hospitalization period.

Methods

Study population. This study was conducted in a single center of the Netherlands (Thoraxcenter, Erasmus MC). All 89 consecutive patients who underwent OCT after stent implantation in native coronary arteries between May 2007 and March 2009 were included. Patients with acute myocardial infarction and long lesions that needed over 50 mm of stent length (n = 33) were excluded. We also excluded 16 patients due to poor OCT images. Finally, 40 patients (45 vessels) with stable angina or unstable angina were included in the study. During the same period of time, 9 patients enrolled in the SECRITT trial were included for evaluation of vProtect® Luminal Shield.⁶ All patients gave informed consent. OCT acquisition. OCT acquisition was performed using a commercially available system for intracoronary imaging (ImageWire, LightLab Imaging, Inc, Westford, Massachusetts). In 5 cases, the occlusive technique was used in which a proximal, low-pressure (0.4 atm) occlusion balloon (Helios, Goodman, Inc., Nagoya, Japan) was inflated with simultaneous distal flush delivery (lactated ringer; flow rate 0.8 mL/sec) to remove blood from the vessel lumen. Images were acquired during a pullback rate of 1.0 mm/sec. In 40 cases, OCT was acquired with the nonocclusive technique. In this case, the ImageWire was positioned distal to the region of interest using a double-lumen catheter (Twin-Pass Catheter, Vascular Solutions, Inc., Minneapolis, Minnesota) that had been previously placed in the artery over a conventional guidewire. The automated pullback was performed at 3 mm/sec (n = 39) or 20 mm/sec (n = 1,C7XR: Lightlab Imaging) while blood was removed by the continuous injection of iso-osmolar contrast (iodixanol 370, Visipaque™, GE Healthcare) at 37°C through the guiding catheter. Data were stored on CD for offline analysis. Definitions. The acute impact of stent implantation in OCT are given in Figure 1. Tissue prolapse was defined as protrusion of tissue between the stent struts without disruption of the continuity of the vessel luminal surface.⁷ Protrusion of tissue between struts was considered tissue prolapse only if the distance from the arc connecting adjacent stent struts to the greatest extent of protrusion was > 50 µm.⁸ Intrastent dissection was defined as disruption of the vessel lumen surface in the stent segment with a visible dissection flap.⁸ Edge dissection was defined as disruption of the vessel lumen surface in the stent edge within the 5 mm proximal and distal segments. Incomplete stent apposition (ISA) was defined as at least one stent strut with detachment from the wall > 1 thickness of the strut for the respective stent and unrelated with a side branch.⁹ Thrombus was defined as an irregular mass protruding into the lumen or an intraluminal mass unconnected from the surface of the vessel wall that had single-free shadowing in the OCT image.¹⁰Quantitative OCT analysis of the acute impact of stent implantation.⁸ The analyzed region comprised the stented segment and the 5 mm proximal and distal persistent segments. The lumen and stent areas were measured at 1 mm intervals. In the case of tissue prolapse, the number of sites with tissue prolapse and the area were measured. Tissue prolapse length was defined as the distance from the arc connecting the adjacent stent struts to the greatest extent of protrusion. The area of tissue protruding between the stent struts was also measured. When there were signs of intrastent dissection, the number of dissection flaps was counted and the length of the flap from its tip to the joint point with the vessel wall was measured. When edge dissection was present, the length of the dissection flap was measured in a similar way as described for the intrastent dissection flap. At sites of ISA, maximum depth in a single cut was measured and the average length was reported. The presence of thrombus was qualitatively assessed and maximum length of thrombus was measured. To account for differences in stent length, the number and total area of tissue prolapse and the number of dissection flaps were corrected according to the stent length and expressed on a per-millimeter basis. Image analysts were blinded to the clinical and procedural characteristics. Clinical follow up. The presence of events (death, myocardial infarction, target-lesion revascularization [TLR], TVR and stent thrombosis) during the hospitalization period following stent implantation was registered in both groups. Myocardial infarction (MI) is defined as chest pain together with ST-elevation or new left bundle branch block and an increase in cardiac enzymes (i.e., creatine kinase-MB fraction of 3 times the upper limit of normal).⁸Statistical analysis. Continuous variables are expressed as mean ± standard deviation. Categorical variables are expressed as percentages. Comparisons between groups were performed with the χ2 test for categorical variables. Continuous variables were compared with the Student t-test when they had a normal distribution and with nonparametric test (Mann-Whitney) when their distribution was not normal. A p-value Results Table 1 shows clinical and procedural characteristics. There were no significant differences between the two groups. Group 2 had different stent types: 6 balloon-expandable bare-metal stents, 1 paclitaxel-eluting stent, 3 zotarolimus-eluting stents and 26 everolimus-eluting stents. The frequency of ACC/AHA Type B2 or C lesions was not significantly different, and the frequencies of predilatation and postdilatation did not differ significantly. However, stent length was significantly larger in Group 2 than in Group 1 (26.2 ± 8.8 and 17.1 ± 5.2 mm, respectively; p = 0.001). Acute impact of stent implantation assessed by OCT (Figure 2). After stenting, the lumen area was 7.9 ± 2.3 mm² in Group 1 and 7.3 ± 1.7 mm² in Group 2 (p = 0.3). The mean and minimum stent areas were 8.0 ± 2.3 and 6.3 ± 2.3 mm² in Group 1 and 7.6 ± 1.9 and 6.0 ± 1.7 mm² in Group 2, respectively. Although all vessels in both groups showed tissue prolapse, the corrected number of tissue prolapse and corrected area by stent length were larger in Group 2 than in Group 1 (Table 2). The vProtect® Luminal Shield had less intrastent dissection than balloon-expandable stents and the corrected number of dissections and average length of intrastent dissection flaps were all lower (Table 2). In addition, there was no edge dissection in Group 1, while in Group 2 the distal and proximal edges presented edge dissection in 14/36 (38.9%) and 10/36 (27.8%) vessels, respectively. Among patients in Group 2, five vessels (14%) showed both proximal and distal edge dissection. The average length of the dissection flap was 515 ± 403 µm. Regarding ISA, 7/9 vessels in Group 1 and 23/36 vessels in Group 2, respectively, showed at least 1 malapposed stent strut; the maximum depth of ISA was 178 ± 156 µm in Group 1 and 267 ± 72 µm in Group 2 (p = 0.03). Images suggestive of thrombus were visible in 2 vessels in Group 1, and 16 in Group 2. The maximum length of visible thrombus was 131 ± 30 µm and 298 ± 122 µm, respectively. In-hospital events. There were no events (death, MI, TLR, TVR or stent thrombosis) during the hospitalization period in either group.

Discussion

In a case report,²² a self-expanding stent showed excellent apposition of the stent to the vessel wall, with no signs of tissue prolapse or edge dissections by IVUS and OCT. This is the first study using OCT to compare the acute impact on the vessel wall between a self-expanding stent and balloon-expandable stents. The main findings are: 1) All stented segments showed tissue prolapse and a very high proportion of patients with intrastent dissection visible by OCT after stent implantation in both groups. Although the frequency of visible tissue prolapse was not significantly different between groups, the average and corrected prolapsed area by stent length was larger in the balloon-expandable stent group. 2) Intrastent and edge dissection were more frequently seen in balloon-expandable stents than in the self-expanding stent. 3) The frequency of ISA did not differ in either group, but the maximum depth of ISA was greater in the balloon-expandable stent group. 4) The difference in acute impact after stenting between two types of stents was not associated with clinical events during hospitalization. According to OCT resolution, this technique has opened new possibilities for the evaluation of stents, allowing a very detailed assessment of strut apposition.^11,12 Furthermore, OCT allows not only qualitative, but also quantitative, evaluation of acute in vivo injury after stenting. In a previously published pathological study, plaque compression by stent struts was observed in 94% of patients and 91% of arterial sections after stent implantation,¹³ while IVUS studies have reported plaque prolapse frequency ranging only from 18–35%.¹⁴ Our group has published the frequency of tissue prolapse by OCT, in which the tissue prolapse within the stented segment was visible in 97.5% of the cases.⁸ Similarly, in the present study, even though the stent types were different, tissue prolapse was visible in all patients. However, in this study, no clinical events during hospitalization occurred, even though the balloon-expandable stent group had visibly larger corrected number of tissue prolapse sites and area by OCT. IVUS has inherent limitations to distinguish between intra-stent dissections and plaque prolapse; OCT can clearly differentiate those two entities.⁸ In our series, despite a high frequency of OCT-visible intrastent dissections and edge dissections in the balloon-expandable stent group, no intrahospital events were registered. In the literature, the relationship between these variables and clinical events at longer follow up continues to be a matter of debate. On one hand, in a study of drug-eluting stents, 30% of proximal edge restenosis developed after 6 months because of local injury outside the stent.¹⁵ But on the other hand, non-flow-limiting edge dissections detected by IVUS have not been associated with an increase in the rates of acute or long-term events or the development of restenosis.^16–18 However, the long-term impact of the presence of intrastent dissection on the incidence of restenosis or stent thrombosis is unknown. As an alternative to balloon-expandable stents, self-expanding stents offer the potential advantages of less barotrauma to the vessel wall, differential expansion and increased flexibility. Compared with balloon-expandable stents, self-expanding stainless steel stents, nitinol stents such as the vProtect® Luminal Shield stent may offer more accurate stent deployment through its use of thermal memory as the expansion mechanism. In native coronary arteries, studies have shown less vessel-wall injury and less edge dissection with nitinol self-expanding stents,^19,20 which is in keeping with our present findings with OCT. Subgroup analysis in the SCORES trial revealed that lesions requiring higher-pressure balloon inflation for implantation had higher rates of restenosis necessitating TLR than did lesions requiring lower-pressure balloon inflation.²⁰ Another recent prospective, randomized trial demonstrated that the incidence of procedural complications such as slow flow, side-branch occlusion and edge dissection were significantly lower in the self-expanding stent group than in the balloon-expandable stent group, and the occurrence of MI tended to be lower in the self-expanding stent group than in the balloon-expandable stent group.¹² In addition, the use of self-expanding stents with low-pressure dilatation instead of balloon-expandable stents could lead to lower incidences of periprocedural non-Q-wave MI. A high inflation pressure during PCI increases the risk for periprocedural non-ST-segment elevation MI and an increased systemic inflammatory state due to microembolization.²¹ This strategy of self-expanding stents could directly reduce the procedural risk by limiting the inflation pressure. Study limitations. This study has several limitations. It is a nonrandomizzed study, and a relatively small population was included in the self-expanding stent group. The two study groups were not matched for lesion severity. Because target lesions were relatively simple in the self-expanding stent group and acute vessel injury might increase in the conventional balloon-expandable stent group, a large prospective study is needed to confirm our observations on the acute impact of self-expanding and balloon-expandable stents.

Conclusions

Although a very high proportion of patients showed tissue prolapse or intrastent dissection visible by OCT after stent implantation in both groups, the self-expanding vProtect Luminal Shield stent appears to be less frequently associated with intrastent and edge dissection than conventional balloon-expandable stents. However, the latter vessel-wall injuries were not associated with in-hospital clinical events. OCT-detectable acute vessel-wall injury after stenting might therefore not be associated with early untoward clinical safety events. Acknowledgments. We thank W. J. van der Giessen, MD, PhD, P. J. de Feyter, MD, PhD, and Carl Schultz, MD for their generous contribution to the study.

References

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From the Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands and the *Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea. Dr. Shin is also the Research Collaborator at Thoraxcenter in Rotterdam, The Netherlands. The authors report no conflicts of interest regarding the content herein. Manuscript submitted March 1, 2010, provisional acceptance given April 26, 2010, final version accepted July 26, 2010. Address for correspondence: Patrick W. Serruys, MD, PhD, Thoraxcenter, Erasmus MC, Bd 585, 's-Gravendijkwal 230, 3015-CE Rotterdam, The Netherlands. E-mail: p.w.j.c.serruys@erasmusmc.nl