Study population
Consecutive ACS patients, who underwent an OCT-guided PCI, using O-SESs or X-EESs and that underwent an 8-month follow-up OCT in our hospital between August 2016 and February 2020, were enrolled in the study. The ACS patients included those with unstable angina pectoris (UAP), non-ST-elevation myocardial infractions (NSTEMIs) and STEMIs. The ACS patients who were treated with DESs (O-SESs or X-EESs) and had a clear OCT image at the 8-month follow-up were included. The choice of those 2 stents depended on each operator’s discretion. The study exclusion criteria were in-stent restenosis, hemodynamic instability, an age less than 18 years, and a life expectancy of less than six months due to a non-cardiac condition. Written informed consent was obtained from all participating patients and the protocol was approved by the Osaka Rosai Hospiral ethics committee. This study conformed to the ethical guidelines outlined in the Declaration of Helsinki.
Stent type
The O-SESs (Orsiro; Biotronik; Bulach, Switzerland) consisted of an ultrathin strut (60µm for stent diameters ≦ 3.0mm and 80µm for stent diameters > 3.0mm) cobalt-chromium metallic stent platform covered by an amorphous, hydrogen-rich, silicon-carbide passive layer and an asymmetric biodegradable poly-L-lactic acid polymer active coating that released sirolimus at a dose of 1.4µg per mm2 of the stent surface, which degraded over a period of 12 to 24 months.[8] On the other hand, the X-EESs (Xience Alpine/Sierra; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut (81µm) cobalt-chromium stent platform that released everolimus from a durable polymer.
Procedural and medical management
PCI for culprit lesions was performed according to the standard techniques. Thrombus aspiration, excimer laser coronary angioplasty (ELCA), direct stenting and post-dilation were left to the operator’s discretion, and the operator referred to the OCT findings to determine the strategy. Before the intervention, all patients were pretreated with 200mg of aspirin and a loading dose of P2Y12inhibitor (300mg of clopidogrel or 20mg of prasugrel). After the intervention, all patients received a dual antiplatelet therapy (DAPT: aspirin 100mg and a P2Y12R inhibitor [75mg of clopidogrel or 3.75mg of prasugrel]) daily for at least 6 months.
OCT image acquisition
The OCT system used in this study consisted of a computer, monitor display, and interface unit (C7 OCT System, Abbott Vascular, Santa Clare, CA, USA). The patients received heparin intravenously before the OCT procedure. Using the C7 OCT system, a conventional angioplasty guidewire (0.014-inch) was advanced distal to the region of interest, then the OCT catheter (Dragonfly, Abbott Vascular, Santa Clara, CA, USA) was advanced over the guidewire beyond the region of interest. During the imaging acquisition, blood was displaced by an injection of contrast media. In general, in the patients presenting with Thrombolysis In Myocardial Infarction (TIMI) flow grades of 2 and 3, the OCT was performed before any intervention, while for cases with a TIMI of 0 or 1, the OCT was performed after a thrombectomy or pre-dilatation using only small sized balloons (≤ 2.0mm balloon).[9, 10] The images were calibrated by an automated adjustment of the Z-offset and the automated pullback was set at 18 or 36mm/s. Data were acquired using a commercially available OCT system (C7 OCT System and Dragonfly imaging catheter, Abbott Vascular, Santa Clare, CA, USA) and were digitally stored.
OCT image analysis
We performed quantitative and qualitative OCT analyses using dedicated software (Off-line Review Software, version E.0.2, Abbott Vascular, Santa Clara, CA, USA). In the pre-procedural, post procedural, and 8-month follow-up OCT data, all cross-sectional images were initially screened for a quality assessment and excluded from analysis if any portion of the stent was out of the screen or if the image quality was considered poor due to residual blood, artifact, or reverberation. Bifurcations with major side branches, which were defined as side branches > 45°, and stent overlapping segments were also excluded.[11] Quantitative (i.e., luminal areas and diameters) and qualitative measurements were performed on every 1mm frame along the entire target segment.
In the pre-procedural OCT data, the assessment of the lesion morphology was performed at the culprit site and the lesions were categorized according to their most prevalent component as follows: (a) plaque rupture and (b) intact fibrous cap. Plaque rupture was defined as the presence of a fibrous cap discontinuity leading to a communication between the inner core of the plaque and the lumen. An intact fibrous cap included both definite (the presence of an attached thrombus overlying an intact and visualized plaque) and probable erosions, defined as a luminal irregularity without a thrombus or thrombus without a superficial lipid or calcified plaque in the proximity of the thrombus. In addition, intact fibrous caps included smooth plaque without evidence of a rupture or thrombus.[12] Thrombus at the culprit site was divided into red thrombus or white thrombus. Red thrombus appeared as a mass with a high backscattering and high attenuation and white thrombus as a homogeneous mass with less backscattering and a low attenuation.[13] We recorded the maximum thrombus area and length of the thrombus within the culprit lesion. The minimum lumen area (MLA) was derived from an automatic lumen segmentation within the region of interest.
In the post-procedural OCT data, the minimum lumen area (MLA) was derived from an automatic lumen segmentation within the stented lesion. In addition, we evaluated the minimum stent area (MSA) at the MLA site and manually traced the stent area by interpolated contours connecting the center point of the luminal surface of each detected metallic strut. The proximal and distal reference areas were measured at the largest lumen within 5mm of the proximal and distal edges. The strut-lumen distance was determined based on automated measurements performed from the center of the strut blooming to the luminal contour of the artery wall. A malapposed strut was defined as having a strut-lumen distance (X-EES > 89µm, O-SES > 67µm, and > 87µm for the 2.25, 2.5, and 3.0 stent diameters and 3.5 and 4.0 stent diameters, respectively). A stent edge dissection was defined as the disruption of the vessel luminal surface with a visible flap at the stent edge or within 5 mm of the proximal and distal reference segments. The in-stent tissue protrusions were divided into 3 categories: smooth protrusions, disrupted fibrous tissue protrusions, and irregular protrusions.[14] Smooth protrusions were defined as the bowing of the plaque into the lumen between the stent struts, without any intimal disruption, appearing as a smooth semicircular arc connecting the adjacent struts, and likely representing a compression of the soft plaque by the stent. Disrupted fibrous tissue protrusions were defined as a disruption of the underlying fibrous tissue protruding from the stent struts into the lumen. Irregular protrusions were defined as protrusions of the material with an irregular surface into the lumen between the stent struts. As the struts are occasionally buried within the intima, we included only in-stent protrusions with a maximal height of ≥ 100 µm for the analysis in the current study.[14]
In the 8-month follow-up OCT data, the neointimal hyperplasia (NIH) thickness was defined as the distance between the endoluminal surface of the strut reflection and the lumen contour. The mean NIH thickness (total NIH thickness divided by the number of total struts), maximum NIH thickness, and minimum NIH thickness was calculated for each lesion.[15] Struts were categorized as malapposed struts, uncovered struts, and covered struts. Malapposed struts were defined in the same way as the post-procedural OCT analysis. Struts were classified as uncovered if any part of the strut was visibly exposed to the lumen. In addition, uncovered struts were categorized as apposed or malapposed struts.[16] The representative images of covered, uncovered and malapposed struts were shown in Fig. 1. The percentage of uncovered struts was calculated as the number of uncovered struts divided by the total number of analyzed struts for each lesion. We compared the OCT parameters including the percentage of uncovered struts, malapposed struts, and the mean NIH thickness between the X-EES and the O-SES groups.
Two independent readers in our institution, who were blinded to the patient information, retrospectively performed quantitative and qualitative OCT analyses. If there was an ambiguous OCT imaging of the coverage, this was argued between the two observers and a final determination was made. To measure inter-observer reproducibility, the percentage of uncovered struts and the percentage of malapposed struts were compared using the Bland-Altman method in 10 randomly selected OCT image.[17]
Statistical analysis
All statistical analyses were performed using JMP version 14 software (SAS Institute, Inc., Cary, North Carolina, USA) and the statistical significance was assessed at a p-level of 0.05. The continuous variables are expressed as the mean ± SD or median (interquartile range) and categorical variables as the count (percentage). For the continuous variables, the difference between the two groups were made with the nonparametric Mann-Whitney U test, and the categorical variables were compared with a Fisher exact test at the lesion level. All variables were analyzed at the lesion level. The pre-procedural, post-procedural, and 8-month follow-up OCT parameters were compared in all lesions.