Vascular Injury After Stenting　- Insights of Systemic Mechanisms of Vascular Repair.

BACKGROUND: The role of circulating progenitor cells (CPC) in vascular repair following everolimus-eluting stent (EES) implantation is largely unknown. The aim of the study was to investigate the relationship between temporal variation in CPC levels following EES implantation and the degree of peri-procedural vascular damage, and stent healing, as measured by optical coherence tomography (OCT).Methods and Results: CPC populations (CD133+/KDR+/CD45low) included patients with stable coronary artery disease undergoing stent implantation, and were evaluated using a flow cytometry technique both at baseline and at 1 week. OCT evaluation was performed immediately post-implantation to quantify the stent-related injury and at a 9-month follow up to assess the mid-term vascular response. Twenty patients (mean age 66±9 years; 80% male) with EES-treated stenoses (n=24) were included in this study. Vascular injury score was associated with the 1-week increase of CD133+/KDR+/CD45low (ß 0.28 [95% CI 0.15; 0.41]; P<0.001) and with maximum neointimal thickness at a 9-month follow up (ß 0.008 [95% CI 0.0004; 0.002]; P=0.04). Inverse relationships between numbers of uncoated and apposed struts for the 9-month and the 1-week delta values of CD133+/KDR+/CD45low (ß -12.53 [95% CI -22.17; -2.90]; P=0.011), were also found. CONCLUSIONS: The extent of vessel wall injury influences early changes in the levels of CPC and had an effect on mid-term vascular healing after EES implantation. Early CPC mobilisation was associated with mid-term strut coverage.

ST-segment elevation myocardial infarction ­ ideal scenario for bioresorbable vascular scaffold implantation?

Bioresorbable vascular scaffolds (BVS) represent a breakthrough technology for percutaneous coronary intervention (PCI). In this context, because of the unique properties of bioresorbable devices, ST-segment elevation myocardial infarction (STEMI) may represent the ideal scenario for BVS implantation. Consistently, 57% of physicians declare they currently use BVS in this group of patients. However, continuous and growing evidence on the good performance of these devices has been actually shown only in small studies with short- and mid-term follow-up. For these reasons, we need data from sufficiently large observational studies, with long-term follow-up, to confirm that BVS can deliver the same results as 2nd-generation drug-eluting stents when using an appropriate implantation technique. In this review, we discuss the potential advantages of BVS implantation in STEMI patients, together with the most recent evidence from clinical studies, highlighting safety and procedural concerns.

Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND: It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS: PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.

Impact of Diabetes Mellitus on Vascular Healing Process After Everolimus-Eluting Stent Implantation: An Optical Coherence Tomography Study.

BACKGROUND/PURPOSE: To study the impact of diabetes mellitus (DM) on vascular healing process after implantation of everolimus-eluting stent (EES). METHODS/MATERIALS: Data from 3 prospective studies (HEAL-EES, REVER, and RESERVOIR), including patients with EES implantation and OCT follow-up, were merged. Differences in vascular healing process assessed by OCT were compared between DM and non-DM using generalized estimating equations. Neointimal proliferation, neointimal signal pattern (high, low, and layered), and uncovered/malapposed struts were evaluated. RESULTS: A total of 96 lesions (61 DM lesions and 35 non-DM lesions) were included. Mean OCT follow-up time was 8.9 ± 1.5 months and comparable between groups. DM were older, high frequently female and acute coronary syndrome, and received smaller stent than non-DM. No differences were observed in quantitative vascular healing process between groups. However, DM exhibited higher low and layered signal pattern neointima compared to non-DM at lesion level (p = 0.030) and cross-section level (p < 0.001). Uncovered/malapposed struts were comparable between groups. CONCLUSIONS: Quantitative vascular healing process was comparable between groups. However, DM was significantly associated with low signal pattern, which is characteristic of focal inflammation, after EES implantation. Further study might be required to study relationship between neointimal signal pattern and clinical events.

Longitudinal Neointimal Distribution Pattern After Everolimus-Eluting Stent Implantation: Insights From Optical Coherence Tomography Study.

BACKGROUND/PURPOSE: Everolimus-eluting stents (EES) are established as latest generation drug eluting stents. However, optical coherence tomography (OCT) assessment of neointimal distribution after EES implantation is lacking. We aimed to assess the longitudinal neointimal distribution pattern after EES implantation using OCT. METHODS: Data from 3 prospective studies (HEAL-EES, REVER and RESERVOIR), including patients with EES implantation and OCT follow-up study, were merged. Analyzed stents were divided into 3 segments of equal length (distal, medial, proximal). Longitudinal neointimal distribution patterns were compared between the 3 segments using generalized estimating equation. Neointimal thickness (NIT), neointimal area obstruction, and uncovered or malapposed struts were analyzed. RESULTS: In total, 86 patients (92 lesions) were analyzed. Time of OCT follow-up was 9.0 ± 1.5 months. NIT was 101.7 ± 65.4 µm and neointimal obstruction area was 12.2 ± 7.6%. The number of assessed struts was the same in all three segments. NIT tended to be higher at the medial segment (108.8 ± 71.1 µm) compared to distal (103.0 ± 63.4 µm) and proximal (93.3 ± 61.1 µm) (p = 0.076). Neointimal area obstruction was significantly different between the 3 segments (12.4 ± 7.5% [distal], 13.1 ± 7.7% [medial], 11.1 ± 7.5% [proximal]; p = 0.037). In the proximal segment, there was a significantly higher frequency of uncovered struts compared to medial and distal segments (3.9% vs. 2.1% vs. 2.5%, p = 0.009). The distribution of malapposed struts was not significantly different. CONCLUSIONS: Distribution of neointimal hyperplasia seems to be different between stent segments, being higher in the medial segment as compared to proximal and distal. Whether this may reflect a response to local pre-interventional plaque burden centrally covered by the stent should be confirmed in a future study. MANUSCRIPT SUMMARY: As optical coherence tomography based assessment of neointimal distribution after everolimus-eluting stent implantation is lacking, we analyzed data of 86 patients (92 lesions) from 3 prospective trials to evaluate neointimal distribution in distal, medial and proximal stent segments. Neointimal hyperplasia seemed to be different between the three segments, with a higher burden in the medial stent segment. Whether this reflects a response to local pre-interventional plaque burden centrally covered by the stent should be confirmed in a future study.

Clinical and angiographic outcomes following percutaneous coronary intervention with sirolimus-eluting stents versus bare-metal stents in hemodialysis patients.

BACKGROUND: Percutaneous coronary intervention for hemodialysis patients has been hampered by the high rate of adverse cardiac events. Our aim was to investigate whether sirolimus-eluting stents (SESs) improve clinical outcomes of hemodialysis patients compared with bare-metal stents (BMSs). STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: 123 consecutive patients on hemodialysis therapy treated with either an SES or BMS. There were 56 patients with 68 lesions treated with SESs between August 2004 and April 2006 (SES group) and 67 patients with 71 lesions treated with BMSs 4 years before approval of SESs in Japan (BMS group). PREDICTOR: SES and BMS implantation for hemodialysis patients with coronary artery disease. OUTCOMES & MEASUREMENTS: Follow-up angiography was performed at 6 to 8 months and clinical follow-up was obtained at 9 months after the procedure. Late lumen loss and major adverse cardiac events, including all-cause death, myocardial infarction, and target-lesion revascularization, were investigated. RESULTS: Clinical follow-up was obtained in all patients. Angiographic follow-up was obtained in 50 patients (89.3%) in the SES group and 50 patients (74.6%) in the BMS group. The SES group had more complex lesions than the BMS group. Quantitative angiographic analysis showed a significant difference for in-stent late lumen loss (SES, 0.62 +/- 0.75 mm; BMS, 1.07 +/- 0.75 mm; P = 0.003). Of angiographic restenosis lesions analyzed, a focal restenotic pattern was observed more frequently in the SES group than the BMS group (SES, 87.5%; BMS, 23.8%; P < 0.001). The rate of major adverse cardiac events was significantly lower in the SES group (n = 14; 25.0%) than the BMS group (n = 26; 38.9%; log-rank P = 0.02). LIMITATIONS: Retrospective study design, small sample size, and a single-center study. CONCLUSIONS: Clinical and angiographic data in the present study suggest that SESs are more effective than BMSs in hemodialysis patients.

Efficacy and safety of transcatheter aortic valve implantation with Edwards SAPIEN 3 and XT in smaller Asian anatomy.

We aimed to compare the efficacy and safety of transcatheter aortic valve implantation (TAVI) using Edwards SAPIEN 3 (S3) valve and SAPIEN XT) in smaller anatomy. The new generation S3 TAVI device has been used worldwide; however, its efficacy and safety in smaller Asian anatomy remain unknown. Between February 2014 and March 2017, 166 consecutive patients (S3, 54; XT, 112) were treated with balloon-expandable TAVI in a single center and their outcomes were analyzed. Median patient age was 85 (range: 81-88) years and mean body surface area was 1.41 ± 0.15 m2. A 23-mm size valve was used in S3 and XT groups (70 vs. 62%, p = 0.224). The transfemoral approach was more frequently used in the S3 than in the XT group (96 vs. 72%, p < 0.001). Although, the minimal luminal diameter of the femoral artery was smaller in the S3 group (5.9 vs. 6.4 mm, p = 0.001), the rates of major (2 vs. 11%, p = 0.226) and minor (11 vs. 5%, p = 0.107) vascular complications did not increase. The frequency of paravalvular leaks (PVL) ≥ 2 was significantly reduced in the S3 group (11 vs. 61%, p < 0.001); however, pre- (24 vs. 91%, p < 0.001) and post- (4 vs. 19%, p < 0.001) dilatations were less frequently performed. Pacemaker implantation incidence did not increase (4 vs. 5%, p = 1.0) and peak velocity of the transcatheter heart valve was significantly higher in the S3 group (2.3 vs. 2.2 m/s, p = 0.046). Device success was high (89 vs. 93%, p = 0.387) while the 30-day all-cause mortality was low (2 vs. 1%, p = 0.583) in both groups. TAVI with the S3 device was safe and effective, with low incidence of vascular complications and reduced PVL, in smaller body-sized Asians.

Serial optical coherence tomography assessment of malapposed struts after everolimus-eluting stent implantation. A subanalysis from the HEAL-EES study.

BACKGROUND: Incomplete stent apposition (ISA) is related to stent thrombosis, which is a serious adverse event. We aim to assess the time-course of ISA after 2nd generation everolimus-eluting stent (EES) implantation. METHODS: In HEAL-EES study, we enrolled 36 patients who underwent percutaneous coronary intervention (PCI) with EES. OCT imaging was performed at baseline and follow-up. Patients were randomized 1:1:1 into 3 groups according to the time in which follow-up was performed: group A (6-month), group B (9-month), and group C (12-month). In this subanalysis, patients who had ISA segments at baseline and/or follow-up OCT were analyzed. RESULT: At baseline, among 41 lesions in 36 patients, 20 lesions in 18 patients had ISA segments and were analyzed. At baseline, there were 3.0% ISA struts in group A (n=8), 2.8% in group B (n=4), and 4.5% in group C (n=8). At follow-up, ISA struts were present in 0.09%, 0.16% and 0.64%; respectively in groups A, B, and C. At follow-up, there was a significant decrease in the frequency of ISA: group A 3.0% vs. 0.09% (p<0.001), group B 2.8% vs. 0.16% (p<0.001), and group C 4.5% vs. 0.64% (p<0.001). In group A, there was one late acquired ISA at follow-up. CONCLUSIONS: In patients undergoing 2nd generation EES implantation, area of acute ISA assessed by OCT, was almost resolved at 6-month follow-up.

Overtime evaluation of the vascular HEALing process after everolimus-eluting stent implantation by optical coherence tomography. The HEAL-EES study.

PURPOSE: Second-generation drug-eluting stent (DES) have shown a better safety and efficacy as compared to first generation DES due to an improved vascular healing process. This process has not been so far evaluated in vivo in an overtime fashion by optical coherent tomography (OCT). We sought to evaluate the vascular healing process after everolimus-eluting stent (EES) implantation at 6, 9 and 12months, by OCT. METHODS: Consecutive 36 patients undergoing percutaneous coronary intervention with EES were randomized 1:1:1 to receive OCT imaging at 6 (group A), 9 (group B) or 12-month follow-up (group C). One patient from group C was excluded because of target lesion revascularization at 1-month, whereas 5 patients withdraw the informed consent. Finally, 30 patients were analyzed. RESULTS: Neointimal thickness was not different between 3 groups (group A: 99.50 [94.06-127.79] µm, group B: 107.26 [83.48-133.59] µm, group C: 127.67 [102.51-138.49] µm; p=0.736). Although the percentage of "uncovered struts" was significantly higher in group A as compared to the other groups (8.0% vs. 4.4% vs. 2.9%, respectively; p=0.180), the ratio of uncovered to total struts per section <30% was similar between 3 groups (0.3% vs. 0.3% vs. 0%, respectively; p=1.000). CONCLUSION: Healing process following EES implantation seems almost completed at 6-month follow-up. These data, which need to be confirmed in a larger study, may support the decision to shorten dual antiplatelet therapy.

Frequency and predictors of thrombus inside the guiding catheter during interventional procedures: an optical coherence tomography study.

Optical coherence tomography (OCT) is able to identify thrombus. We detect the frequency of thrombus inside the guiding catheter by OCT and its relationship with clinical and procedural factors. We screened 77 patients who underwent OCT pullbacks. Only patients with visible guiding catheter were finally included (35) and divided into thrombus (21) or no-thrombus group (14). Patients within thrombus group were mostly males (100 vs. 71 %, p = 0.05), with acute coronary syndrome (76 vs. 36 %, p = 0.02) and received more frequently percutaneous coronary intervention (86 vs. 43 %, p = 0.01) as compared to other group. A second dose of heparin was more frequently administered in thrombus than in other group (86 vs. 50 %, p = 0.01). Time between first heparin administration and OCT pullback (41[28-57] vs. 20 min [10-32], p = 0.001), time elapsed from second heparin administration and OCT pullback (29 [19-48] vs. 16 min [12-22], p = 0.002) and total procedural time (47 [36-69] vs. 31 min [26-39], p = 0.005) were longer in thrombus compared to other group. At multivariate analysis, total procedural time and time between first heparin administration and OCT pullback were only predictors of intra-catheter thrombus (HR 0.6 [0.3-0.9], p = 0.03 and HR 1.9 [1.1-3.2], p = 0.02, respectively). Thrombus inside guiding catheter may be a frequent finding in long interventional procedure. Future studies are warranted to determine its clinical impact.

Very Late Scaffold Thrombosis: Intracoronary Imaging and Histopathological and Spectroscopic Findings.

BACKGROUND: Bioresorbable scaffolds provide transient lumen support followed by complete resorption. OBJECTIVES: This study examined whether very late scaffold thrombosis (VLScT) occurs when resorption is presumed to be nearly complete. METHODS: Patients with VLScT at 3 tertiary care centers underwent thrombus aspiration followed by optical coherence tomography (OCT). Thrombus aspirates were analyzed by histopathological and spectroscopic examination. RESULTS: Between March 2014 and February 2015, 4 patients presented with VLScT at 44 (case 1), 19 (cases 2 and 4), and 21 (case 3) months, respectively, after implantation of an Absorb Bioresorbable Vascular Scaffold 1.1 (Abbott Laboratories, Abbott Park, Illinois). At the time of VLScT, all patients were taking low-dose aspirin, and 2 patients were also taking prasugrel. OCT showed malapposed scaffold struts surrounded by thrombus in 7.1%, 9.0%, and 8.9% of struts in cases 1, 2, and 4, respectively. Scaffold discontinuity with struts in the lumen center was the cause of malapposition in cases 2 and 4. Uncovered scaffold struts with superimposed thrombus were the predominant findings in case 3. OCT percent area stenosis at the time of VLScT was high in case 1 (74.8%) and case 2 (70.9%) without evidence of excessive neointimal hyperplasia. Spectroscopic thrombus aspirate analysis showed persistence of intracoronary polymer fragments in case 1. CONCLUSIONS: VLScT may occur at advanced stages of scaffold resorption. Potential mechanisms specific for VLScT include scaffold discontinuity and restenosis during the resorption process, which appear delayed in humans; these findings suggest an extended period of vulnerability for thrombotic events.

Drug-eluting stents and acute myocardial infarction: A lethal combination or friends?

Primary percutaneous coronary intervention is the preferred reperfusion strategy for patients presenting with ST-segment elevation myocardial infarction (STEMI). First generation drug-eluting stents (DES), (sirolimus drug-eluting stents and paclitaxel drug-eluting stents), reduce the risk of restenosis and target vessel revascularization compared to bare metal stents. However, stent thrombosis emerged as a major safety concern with first generation DES. In response to these safety issues, second generation DES were developed with different drugs, improved stent platforms and more biocompatible durable or bioabsorbable polymeric coating. This article presents an overview of safety and efficacy of the first and second generation DES in STEMI.

Predominant microvessel proliferation in coronary stent restenotic tissue in patients with diabetes: insights from optical coherence tomography image analysis.

BACKGROUND: Coronary optical coherence tomography (OCT) enables virtual depiction of histological findings of in-stent restenotic tissue. The aim of this study was to investigate the microvessel proliferation within in-stent restenotic tissue and the influence of diabetes mellitus (DM). METHODS: We examined 54 in-stent restenotic coronary artery lesions (stenotic area>50%) from 50 consecutive patients including 28 with DM (56%) and 9 insulin-treated DM patients (18%); who underwent coronary time-domain OCT imaging with automatic pull back (1mm/s, 20 frames/s). Microvessels were defined as low-signal cavities with a diameter of 50-150 microns and a trajectory parallel to the lumen recognized on 3 consecutive cross-sectional OCT image frames. The microvessel index was calculated as the number of frames with microvessel/total number of frames × 100. Patients were stratified into 3 groups: 1) without microvessels, 2) with a low (< median value) microvessel index, 3) with a high microvessel index. RESULTS: Microvessels were detected in 566 frames (3.1%) from 26 lesions (48%) in 24 patients (48%). A greater incidence of DM and higher serum glucose levels were observed in the high microvessel index group (DM: 42% vs 58% vs 83%, p=0.049; serum glucose level: 118.2 ± 44.6 vs 122.6 ± 31.0 vs 172.8 ± 63.1mg/dL, p=0.03 between low and high microvessel index group, p=0.005 between no microvessel and high microvessel index group). CONCLUSIONS: Microvessel formation may be a unique pathophysiological factor of in-stent restenoses in patients with DM.

Difference of culprit plaque composition between patients with and without pre-infarction angina: an intravascular ultrasound radiofrequency analysis.

AIMS: This study was performed to assess the differences in culprit plaque composition between patients with and without pre-infarction angina (PA) by using spectral analysis of intravascular ultrasound (IVUS) radiofrequency (RF) data. METHODS AND RESULTS: Of 57 patients consecutively admitted to our institution with acute myocardial infarction, pre-intervention IVUS RF data of culprit plaques were obtained and analysed in 35 patients after percutaneous aspiration thrombectomy. Among the 35 patients, 21 patients had PA. Culprit plaques of patients without PA consisted of a higher percentage of the necrotic core component than those with PA (minimum lumen area [MLA]) site, 21.2+/-8.9% versus 9.9+/-9.8%, p=0.0015; entire culprit lesion, 18.9+/-6.3% versus 12.0+/-9.6%, p=0.023). In contrast, culprit plaques of patients with PA contained a higher percentage of the fibrofatty component than those without PA (MLA site, 21.0+/-12.0% versus 11.5+/-7.6%, p=0.013; entire culprit lesion, 16.8+/-7.9% versus 12.1+/-5.5%, p=0.062). There was no significant difference in quantitative parameters between the patients with and without PA. CONCLUSIONS: Culprit plaques of patients with PA were different from those without PA. Plaque composition may play an important role in the occurrence of PA.

Relationship between coronary artery remodeling and plaque composition in culprit lesions: an intravascular ultrasound radiofrequency analysis.

BACKGROUND: The relationship between coronary artery remodeling and culprit plaque composition in vivo has not been fully evaluated by spectral analysis of intravascular ultrasound (IVUS) radiofrequency (RF) data. METHODS AND RESULTS: IVUS RF analyses were performed for 56 consecutive de novo culprit lesions of 52 patients undergoing percutaneous coronary intervention. Remodeling of culprit lesions was determined using the remodeling index (RI), calculated as the external elastic membrane area of the minimum lumen area (MLA) site divided by that of the proximal reference site. Positive remodeling was defined as RI >1.05, intermediate remodeling as 0.95< or = RI < or =1.05 and negative remodeling as RI <0.95. Among the 56 lesions, positive remodeling was detected in 24, intermediate remodeling in 16, and negative remodeling in 16. At MLA sites, positive remodeling lesions had a larger percentage of the fibrofatty component than negative remodeling lesions (22.5+/-10.3% vs 10.4+/-6.6%, p=0.0001), whereas the latter contained a larger percentage of the dense calcium component than the former (2.8+/-2.9% vs 8.4+/-7.0%, p=0.016). CONCLUSIONS: Culprit plaques with positive remodeling have a large lipid burden, whereas those with negative remodeling contain a large amount of calcium.