Patient characteristics

The patients’ characteristics at the PCI procedure are listed in Table 1. Prescriptions and laboratory data for the study patients are shown in Table 2. Twenty-three patients (76.6%) received dual anti-platelet therapy and six patients (20.0%) used oral anticoagulants for atrial fibrillation. All of patients who used oral anticoagulants were prescribed single anti-platelet therapy. A patient received initial single anti-platelet therapy due to history of severe intestinal hemorrhage. There was not significant difference in dual anti-platelet therapy duration between BP-EES and DP-EES group. There were no significant differences in pre- and post-procedural laboratory data between the BP-EES and DP-EES groups, except for serum triglyceride levels.

Table 1 Patients’ clinical characteristicsTable 2 Prescriptions and laboratory data before and after procedureLesion characteristics and procedures

Lesion characteristics assessed by FD-OCT are shown in Table 3. The median calcium arc was 293.8° (253.8–326.0°) and the median calcium thickness was 1.35 mm (1.15–1.60 mm). Five patients required lesion modification using atherectomy devices before initial FD-OCT observation because the imaging catheter could not pass the severe stenosis. Rotational atherectomy was used for lesion modification in 26 patients (86.7%) and orbital atherectomy was used in the other patients. The total length of the deployed stents was 32 mm (23–38 mm) and the median final TIMI flow grade was 3 (3–3). Two patients had reduced TIMI flow (grade 2) at final angiography.

Table 3 Lesion characteristics, procedural data, and FD-OCT analysis at PCIFD-OCT analysis of deployed stents at baseline

The baseline FD-OCT parameters are shown in Table 3. A total of 6234 paired struts in 956 cross-sections were detected in baseline FD-OCT images. The median S–V distance of the detected struts was 72 μm (50–101 μm), 401 struts (6.4%) were malapposed, and the median S–V distance of these malapposed struts was 289 μm (237–392 μm).

Regarding the classification of plaque morphology behind the struts, 92 struts (22.9%) were categorized as mod-Ca, 107 (26.7%) as non-mod-Ca, and 202 (50.4%) as non-Ca. In addition, 108 mod-Ca struts were categorized as Ca-Fx (27 struts; 6.9%) or A-Ca (63 struts; 16.1%). Intraobserver reproducibilities for interpreting plaque morphology behind the struts were 95.9% and 93.4%, respectively, and the interobserver reproducibility was 86.8%.

Follow-up data and follow-up FD-OCT analysis.

Follow-up data are shown in Table 4. The median follow-up duration was 351 days (284–407 days). One patient underwent revascularization at follow-up due to restenosis of the stent edge. Of the 401 malapposed struts, 31 (7.7%) were excluded from the statistical analysis because of unclear images induced by inadequate blood flush or wire shadow at follow-up FD-OCT. Nine struts (2.2%) were eliminated because of a restenosed cross-section (lumen area < 3.0 mm2). Finally, 361 analyzable paired struts were detected in initial and follow-up FD-OCT images, including 308 struts (85.3%) with resolved ASM and median residual S–V distance 311 μm (149–420 μm). In addition, 311 of the 361 struts (86.2%) were covered with neointima and 301 (83.4%) had adequate vascular healing. The median neointimal thickness was 64 μm (36–132 µm). The intraobserver reproducibilities for interpreting resolution of ASM were 90.9% and 93.6%, respectively, and the interobserver reproducibility was 82.7%. The intraobserver reproducibilities for interpreting neointimal coverage were 88.7% and 93.6%, respectively, and the interobserver reproducibility was 77.7%.

Table 4 Follow-up FD-OCT analysis of acute malapposed strutsEffects of plaque morphologies and DES type to the tissue response.

Multivariate linear regression analysis using a generalized estimated equation revealed that adequate vascular healing was significantly better in patients who received BP-EES compared with those who received DP-EES (odds ratio [OR] 3.691, 95% confidence interval [CI] 1.175–11.592, P = 0.025) (Fig. 3). Follow-up duration, S–V distance, and cross-sectional lumen area were also significant factors associated with adequate vascular healing. Additionally, adequate vascular healing was associated with the plaque morphology behind the struts (mod-Ca vs non-mod-Ca: OR 2.833, 95% CI 1.491–5.384, P = 0.001; non-Ca vs non-mod-Ca: OR 1.248, 95% CI 0.440–3.543, P = 0.677). In a regression model adjusting for follow-up duration, S–V distance, and cross-sectional lumen area, adequate vascular healing was significantly associated with DES type and plaque morphology behind the struts, while adequate vascular healing was best for mod-Ca with BP-EES (P for interaction = 0.004) (Fig. 4).

Fig. 3

The estimated effect of calcium modification and stent selection to predict the adequate vascular healing using multivariate linear regression analysis via generalized estimated equation. Continuous variables were employed to estimate adequate vascular healing as 1-standard deviation (SD) increase in this model. The SDs for each parameter in malapposed struts were 114 days for follow-up duration, 141 μm for S–V distance, and 2.91 mm2 for cross-sectional lumen area. BP-EES   biodegradable polymer everolimus-eluting stent, DP-EES  durable polymer everolimus-eluting stent, mod-Ca modified calcium, non-mod-Ca   non-modified calcium, non-Ca non-calcium, S–V distance stent–vessel lumen distance

Fig. 4

Effect modification model predicting adequate vascular healing of plaque morphologies and stent type using regression analysis via generalized estimating equation, adjusting for follow-up duration, S–V distance, and cross-sectional lumen area. Adequate vascular healing was significantly associated with stent type and plaque morphology behind the struts, comparing DP-EES with non-mod-Ca as reference (BP-EES on mod-Ca: OR 10.312, 95% CI 2.211–48.090, P = 0.003; BP-EES on non-Ca: OR 4.620, 95% CI 0.885–24.114, P  = 0.069; BP-EES on non-mod-Ca: OR 3.710, 95% CI 0.629–21.877, P  = 0.148; DP-EES on mod-Ca: OR 2.860, 95% CI 1.226–6.672, P  = 0.015; DP-EES on non-Ca: OR 1.249, 95% CI 0.357–4.374, P  = 0.728; P for interaction  = 0.004)

Additional analysis of the detailed classification of plaque morphology behind the struts identified stent type, follow-up duration, S–V distance, cross-sectional lumen area as being significantly associated with adequate vascular healing (BP-EES vs DP-EES: OR 3.832, 95% CI 1.207–12.168, P = 0.023; follow-up duration: OR 2.311, 95% CI 1.174–4.548, P  = 0.015; S–V distance: OR 0.645, 95% CI 0.433–0.961, P  = 0.031; cross-sectional lumen area: OR 0.665, 95% CI 0.444–0.996, P = 0.048). Plaque morphology behind the struts was significantly associated with adequate vascular healing (Ca-Fx vs non-mod-Ca: OR 4.654, 95% CI 1.600–13.539, P = 0.005; A-Ca vs non-mod-Ca: OR 2.216, 95% CI 1.099–4.469, P = 0.026; non-Ca vs non-mod-Ca: OR 1.229, 95% CI 0.427–3.542, P = 0.702).

In struts with neointimal coverage (311 struts), the regression model demonstrated no significant association with NIT among stent types, plaque morphologies behind the struts, S–V distance, and cross-sectional lumen area, whereas follow-up duration was significantly associated with NIT (Table 5). However, follow-up duration and S–V distance were significantly associated with tissue growth in a mixed-effect model (Table 5). Stent type and cross-sectional lumen area could not significantly predict tissue growth. Plaque morphology behind the strut was significantly associated with tissue growth (mod-Ca vs non-mod-Ca; B = 79.7, 95% CI 13.4–146.0, P = 0.019; non-Ca vs non-mod-Ca: B = 21.9, 95% CI  − 22.5 to 66.4, P = 0.333).

Table 5 Mixed-effect model to predict NIT and tissue growth