One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Safety and feasibility of intravascular ultrasound-guided robotic percutaneous coronary intervention.

OBJECTIVE: Previous studies have demonstrated the benefit of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for preventing longitudinal geographic miss (LGM). However, it is yet unclear whether IVUS guidance is useful for robotic-PCI (robotic-assisted perctaneous coronary intervention [R-PCI]). METHODS: A total of 58 consecutive patients with stable angina who underwent IVUS-guided R-PCI were enrolled. The stent landing position was angiographically marked using a balloon marker before stenting, followed by measurements of the expected stent length using balloon pullback. Subsequently, prestenting IVUS was performed to determine stent landing. All pre-PCI IVUS images were assessed for lesion length and percent plaque volume (%PV) using both IVUS and angiographic marking. LGM was defined as a residual %PV >50% at either the distal or proximal stent edge, any stent edge dissection, or additional stent deployment immediately after stenting. RESULTS: The included patients had an average age of 67.1 ± 10.1 years. IVUS guidance had significantly longer lesion lengths compared with angiographic marking. Based on IVUS-guided stent deployment, nine cases exhibited LGM immediately after stenting. IVUS-marked landing points had a significantly smaller %PV and significantly larger lumen area compared with those for angiography. CONCLUSION: IVUS-guided R-PCI was well-tolerated and may be better at preventing LGM compared with angiography-guided R-PCI.

Periprocedural and 30-day outcomes of robotic-assisted percutaneous coronary intervention used in the intravascular imaging guidance.

In recent years, there have been several reports on robotic-assisted percutaneous coronary intervention (R-PCI), but few studies have been conducted on R-PCI performed under intravascular imaging guidance. To elucidate the periprocedural and postoperative 30-day outcomes of intravascular imaging-guided R-PCI, we performed a retrospective observational study on all patients in 102 consecutive cases who underwent R-PCI under intravascular imaging guidance at a single center in Japan from June 12, 2019 to February 18, 2021. The primary end point was 30-day survival, and the secondary end point was the incidence of complications. Intravascular imaging-guided R-PCI was performed 110 times in total on 125 lesions. The medians of procedural time, fluoroscopy time, contrast volume, patient entrance skin dose, and radiation exposure to the main operator were 49 min, 16 min, 67 mL, 0.62 Gy, and 0 µSv, respectively. Furthermore, 60.0% of target lesion branches were American College of Cardiology Foundation/American Heart Association classification type B2 or type C. However, in all cases, lesion dilatation was successful, and the final Thrombolysis in Myocardial Infarction flow grade was 3. The combination of manual operation was required in 12.7% of all cases, but 30-day survival was confirmed in all cases. There were two problems at the puncture site. One small distal branch artery dissection occurred due to manual operation, but no cardiovascular events (myocardial infarction, stroke) occurred and no target lesion restenosis was observed within 30 days of R-PCI. Hence, R-PCI using intravascular imaging demonstrated highly satisfactory treatment outcomes, and no complication caused by robotic operation was observed.

Predictors of Irregular Protrusion After Everolimus-Eluting Stent Implantation in Patients with Stable Coronary Artery Disease.

This study aimed to investigate clinical and preintervention optical coherence tomography (OCT) findings to predict irregular protrusion (IRP) immediately after stent implantation.We evaluated 84 lesions treated with cobalt-chromium everolimus-eluting stent (CoCr-EES) from the MECHANISM Elective study. Patients were divided into two groups according to the presence of IRP [IRP: n = 16, non-IRP: n = 68]. Optical coherence tomography images before intervention and immediately after stenting were evaluated with standard qualitative and quantitative OCT analyses.Total cholesterol and the prevalence of ruptured plaque before intervention were significantly higher in the IRP group than in the non-IRP group [199 ± 37 mg/dL versus 176 ± 41 mg/dL; P = 0.022, 31% versus 7%; P = 0.008]. Total lipid length tended to be longer in the IRP group than in the non-IRP group [19.6 ± 9.2 mm versus 15.5 ± 9.3 mm; P = 0.090]. The prevalence of ruptured plaque, and total cholesterol levels were independent predictors of IRP immediately after stenting by multivariate logistic regression analysis [OR: 4.6, 95% confidence interval: 1.01-21.23, P = 0.048, OR: 1.02, 95% confidence interval: 1.00-1.03, P = 0.046]. IRP post-CoCr-EES implantation was completely resolved at follow-up OCT.The prevalence of ruptured plaque before intervention and total cholesterol levels were independent predictors of IRP after CoCr-EES implantation in patients with stable coronary artery disease.

Kounis syndrome caused by protamine shock after coronary intervention: A case report.

We report a case of Kounis syndrome that led to shock after protamine administration during percutaneous coronary intervention (PCI). A man in his 50s was admitted to the nearest hospital following the onset of acute myocardial infarction. Coronary angiography showed a single-vessel lesion in the left anterior descending artery (LAD). He was admitted for PCI. After heparin administration, the procedure was completed by implantation of a coronary stent with the usual procedure. For hemostasis, following protamine administration, the patient went into shock. Subsequently, electrocardiography showed bradycardia with ST-segment elevation at leads II, III, aVF, and V3-6. Cardiopulmonary resuscitation was started immediately. As pulseless electrical activity continued, extracorporeal membrane oxygenation (ECMO) was introduced. Coronary angiography demonstrated coronary spasm in the LAD. He was withdrawn from the ECMO on day 7. His intradermal tests were positive for protamine in the convalescent phase. The patient was diagnosed with protamine shock and type I Kounis syndrome. Protamine shock is not uncommon, but Kounis syndrome may be hidden in it. Thus, similar cases should not be treated as a simple protamine shock. .

Comparison of serial optical coherence tomography imaging following aggressive stent expansion technique: insight from the MECHANISM study.

To compare early vascular healing following cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation between groups with or without aggressive stent expansion in patients treated by CoCr-EES for stable coronary artery disease (CAD). Seventy-one stable CAD lesions underwent CoCr-EES implantation and analysis of serial optical coherence tomography (OCT) images obtained post-procedure and at early-term (1- or 3-month) follow-up. The endpoints of this study were neointimal thickness at the time of 1- or 3-month OCT and presence and healing of stent edge dissection. Aggressive stent expansion was defined as a lesion complying with ILUMIEN III sizing protocol; that is, external elastic lamina (EEL) diameter minus maximum balloon diameter ≤ 0.25 mm.  Comparing groups with and without aggressive stent expansion, median neointimal thickness at 1 and 3 months after CoCr-EES implantation was similar (1 month: 0.031 mm vs. 0.041 mm, respectively, p = 0.27; 3 months: 0.036 mm vs. 0.040 mm, respectively, p = 0.84). Regarding stent edge findings, the presence of any stent edge dissection immediately after percutaneous coronary intervention was also similar between the groups (25% vs. 15%, respectively; p = 0.30) and most stent edge dissections resolved completely within 3 months, regardless of location or dissection severity. After 1 year, no clinically driven target lesion revascularization or stent thrombosis was observed in either cohort. Even after aggressive stent expansion, early neointimal proliferation appeared modest with CoCr-EES implantation, and most stent edge dissections had resolved by 3 months. These findings may support the feasibility of EEL-based sizing by pre-stenting OCT.

Clinical outcomes of patients treated using very short duration dual antiplatelet therapy after implantation of biodegradable-polymer drug-eluting stents: rationale and design of a prospective multicenter REIWA registry.

Several studies have demonstrated the safety and feasibility of short (3-6 months) and very short duration (< 2 months) dual antiplatelet therapy (DAPT) in patients with a durable-polymer drug-eluting stent (DP-DES). However, the clinical importance of using very short duration DAPT has yet to be established in patients with a biodegradable polymer drug-eluting stent (BP-DES). The aim of this REIWA registry (multicenter and prospective registry; investigation of clinical outcomes of patients treated with short duration dual antiplatelet therapy after implantation of biodresorbable-polymer drug-eluting stent: a multicenter, prospective registry from Iwate medical university affiliated hospitals) is to determine the safety and feasibility of using 1-month DAPT followed by P2Y12 inhibitor monotherapy in patients after BP-DES implantation. This study is an observational, prospective, multicenter registry encompassing the entire local medical region of Iwate Prefecture (northern area of mainland Japan). A total of 1200 patients who underwent successful PCI with a novel thin strut BP-DES (Synergy, Ultimaster or Orsiro) and are considered to be appropriate patients for very short DAPT, are registered and subsequently administered 1-month DAPT followed by P2Y12 inhibitor monotherapy (clopidogrel 75 mg/day or prasugrel 3.75 mg/day). The primary endpoint was a composite of cardiovascular and bleeding events, which included cardiovascular death, spontaneous myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke, or TIMI major or minor bleeding at 12 months. The REIWA registry (UMIN000037321) will demonstrate both the safety and feasibility of using 1-month DAPT in patients with BP-DES. Furthermore, results of this study will also be able to provide supportive evidence for P2Y12 inhibitor monotherapy after 1-month DAPT following BP-DES implantation.

Cut-off value of strut-vessel distance for the resolution of acute incomplete stent apposition in the early phase using serial optical coherence tomography after cobalt-chromium everolimus-eluting stent implantation.

OBJECTIVE: The purpose of this study was to identify a cut-off value to predict the resolution of incomplete-stent-apposition (ISA) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation at early follow-up. BACKGROUND: To date, appropriate stent apposition at the acute period using intracoronary imaging has been recommended because persistent ISA is considered to be a risk factor for stent thrombosis. We examined the indices for resolving acute ISA. In particular, we determined the cut-off value for strut vessel distance (SV-distance) as visualized by optical coherence tomography (OCT) at 8 months after CoCr-EES implantation. However, the cut-off value of SV-distance for the earlier resolution of ISA is unclear. METHODS: A total of 95 cases and 103 stents were registered in the MECHANISM Elective substudy. The SV-distance was measured at the deepest site of the target malapposition and every 1 mm from the proximal edge to the distal edge of the mal-apposed area using OCT. Cut-off values for ISA resolution at 1 and 3 months were estimated by SV-distance using receiver operating characteristic analysis. RESULTS: The total number of analyzed struts was 14,418 at the 1-month follow-up and 11,986 at the 3-month follow-up. The optimal SV-distance cut-off values just after stent implantation to predict ISA resolution were 185 µm at the 1-month follow-up and 195 µm at the 3-month follow-up. CONCLUSION: For resolution of ISA, SV-distance cut-off values of 185 µm at 1 month postimplantation and 195 µm at 3 months postimplantation can be used as the index of endpoint of the percutaneous coronary intervention.

Cut-off value of mal-apposition volume and depth for resolution at early phase of acute incomplete stent apposition after CoCr-EES implantation.

The purpose of this study was to clarify a cut-off value for acute incomplete stent apposition (ISA) volume and maximum-depth to predict ISA resolution at 1- and 3-month follow-up in patients treated with cobalt-chromium everolimus-eluting stents. In total, 95 cases and 103 stents were registered in the MECHANISM-Elective sub-study. Acute ISA-volume was measured by the trapezoid rule. ISA resolution of cut-off value at 1- and 3-month was estimated by ISA-volume and maximum-depth using receiver operatorating characteristic curve analysis. The total number of analysed acute ISAs was 202 in the 1-month group and 225 in the 3-month group. A total of 123 ISAs at 1-month and a total of 169 ISAs at 3-month had been resolved. The cut-off value of ISA resolution by ISA-volume was 0.169 mm3 at 1-month (AUC: 0.725, sensitivity: 72.2%, specificity: 61.0%) and 0.295 mm3 at 3-month (AUC: 0.757, sensitivity: 75.0%, specificity: 60.4%). The cut-off value of ISA resolution by ISA maximum-depth demonstrated was 0.285 mm at 1-month (area under curve (AUC): 0.789, sensitivity: 70.9%, specificity: 69.9%) and 0.305 mm at 3-month (AUC: 0.663, sensitivity: 60.7%, specificity: 66.9%). Incidence of ISA resolution was significantly lower in combination with cut-off values of ISA-volume and maximum-depth (33%, p < 0.001, at 1-month; 56%, p = 0.003, at 3-month). Combining the cut-off value of ISA-volume with the maximum-depth might be helpful to consider the endpoint of the PCI procedure.

Coronary risk factors associated with OCT macrophage images and their response after CoCr everolimus-eluting stent implantation in patients with stable coronary artery disease.

BACKGROUND AND AIMS: The aim of this study was to evaluate the accumulation of optical coherence tomography (OCT)-macrophages and OCT findings after CoCr everolimus-eluting stent placement, in addition to coronary risk factors. METHODS: A total of 89 lesions in 89 patients were registered in the 1- and 3-month cohort of the multi-centre study. Lesion characteristics and post-procedure OCT images were evaluated immediately and 1 and 3 months after stenting. Patients were divided into low and high macrophage grade groups based on the median macrophage grade. RESULTS: Low-density lipoprotein cholesterol (LDL-C) levels, the prevalence of diabetes mellitus, HbA1c and blood glucose levels in the high macrophage grade group were significantly higher than in the low macrophage grade group (p = 0.025, p = 0.040, p = 0.032, and p = 0.010). Moreover, total lipid arc and length and number of thin-cap fibroatheromas (TCFAs) in the high macrophage grade group were significantly higher than in the low macrophage group (p = 0.008, p = 0.002, and p = 0.012). After CoCr everolimus-eluting stenting, there was a trend towards a greater number, height, and area of irregular protrusions in the high macrophage grade group compared to the low macrophage grade group (p = 0.091, p = 0.059, and p = 0.085). Multivariate logistic regression analysis showed that diabetes mellitus was a significant predictor of high macrophage grades (odds ratio: 2.8, 95% CI: 1.1-7.3, p = 0.030). CONCLUSIONS: The accumulation of OCT-macrophages was associated with diabetes mellitus in patients with coronary artery disease. Moreover, macrophage accumulation and diabetes mellitus may be associated with irregular protrusions just after stenting.

Clinical and pathological characteristics of homogeneous and nonhomogeneous tissue of in-stent restenosis visualized by optical coherence tomography.

BACKGROUND: Although it is known that in-stent restenosis (ISR) patterns appear homogeneous or nonhomogeneous by optical coherence tomography (OCT), interpretations of the ISR inflammatory response, of the OCT image, and its pathological implications are unclear. The aim of this study was to use OCT to characterize ISR and its inflammatory index in patients after coronary stenting. METHODS: OCT was performed at follow-up in 100 angiographic ISR lesions. ISR lesions were divided into two groups: (a) homogeneous (n=48) and (b) nonhomogeneous (n=52) image groups. We assessed the ISR images produced by OCT for tissue heterogeneity and neo-intimal hyperplasia using the normalized standard deviation of OCT signal-intensity (OCT-NSD) observed in neo-intimal hyperplasia tissue. In some patients with a nonhomogeneous OCT image, we collected pathological tissue. RESULTS: The prevalence of drug-eluting stents was 48% in the nonhomogeneous group and 29% in the homogeneous group (P=0.05). The OCT-NSD value in the nonhomogeneous group (0.223±0.019) was significantly higher than that in the homogeneous group (0.203±0.025; P<0.0001). Pathological tissue showed fibrin thrombi with infiltrating macrophage in 12 cases of nonhomogeneous ISR. The area under the receiver operating characteristic curve for the prediction of a nonhomogeneous image was 0.73 for OCT-NSD (95% confidence interval: 0.62-0.83: P<0.0001). The odds ratio for the prediction of a nonhomogeneous image was 3.47 (95% confidence interval: 1.18-10.2: P=0.02) for smoking by logistic regression analysis. CONCLUSION: Nonhomogeneous ISR visualized by OCT showed a high OCT-NSD value, which was a useful predictor for nonhomogeneous images. Moreover, the nonhomogeneous ISR image visualized by OCT may show chronic inflammation and fibrin thrombi.

Morphological and quantitative analysis of vascular wall and neointimal hyperplasia after coronary stenting: comparison of bare-metal and sirolimus-eluting stents using optical coherence tomography.

BACKGROUND: It has been suggested that sirolimus-eluting stents (SES) provoke a more sustained inflammatory response (IR) in neointimal hyperplasia (NIH). The purpose of this study was to compare morphological vessel characteristics, including post-stent IR in NIH, between patients with SES and bare metal stents (BMS) using optical coherence tomography (OCT). METHODS AND RESULTS: Thirty-seven patients underwent OCT at their post-stent follow-up. OCT signal-intensity deviation (normalized standard-deviation; OCT-NSD) values in NIH were compared between the 2 groups. In addition, the serum concentration of high-sensitivity C-reactive protein (hs-CRP) was measured. Stent-malapposition rate (1.78% vs. 0.7%; P = 0.016), uncovered stent-strut rate (16% vs. 3.7%; P = 0.0002), peri-stent ulcer like appearance (PSUA; 50% vs. 0%; P = 0.006) were all significantly higher in the SES group than in the BMS group, respectively. The OCT-NSD value was also significantly higher in the SES group than in the BMS group (0.213 ± 0.005 vs. 0.198 ± 0.005; P < 0.001), as was the hs-CRP level (2.54 ± 1.89 vs. 0.64 ± 0.3 mg/L; P = 0.0006). In addition, a significant positive correlation was found between hs-CRP and OCT-NSD (r = 0.471; P = 0.0025). CONCLUSIONS: PSUA-morphology was specific in the SES group, and higher levels of OCT-NSD and hs-CRP after SES implantation suggest sustained IR in NIH compared with following BMS implantation. These different characteristics may be some of the background that promotes thrombus formation as a late-stage post-stent complication of SES.

Chronic thrombus occlusion after bare metal stenting in a patient with acute coronary syndrome visualized by optical coherence tomography.

We present a case of chronic thrombus occlusion visualized by optical coherence tomography (OCT) in a patient following bare metal stent (BMS) implantation. A 74-year-old Japanese man was treated with single BMS implantation for acute coronary syndrome. The second follow-up angiography demonstrated no restenosis at the BMS site in the convalescent phase before discharge. A third coronary angiography at 6 months after BMS implantation showed sub-total occlusion at a site just proximal to the BMS. OCT was performed to evaluate in-stent restenosis. OCT demonstrated an organized thrombus-like image containing a micro-channel in the target lesion. Repeat percutaneous coronary intervention (PCI) was performed with a distal protection device and we were able to aspirate some tissue from the culprit lesion. Pathological examination of this tissue revealed an organized fibrin thrombus with angiogenesis. Phosphotungstic acid hematoxylin staining and CD68 immunological staining were positive in this tissue. Moreover, immunological staining for CD34 was positive in the micro-channel of this tissue, suggesting chronic build up. This case demonstrated that chronic, organized thrombus formation is a possible cause of restenosis after BMS implantation in the convalescent phase, and that OCT is a useful modality to discriminate thrombus formation from regular neo-intimal hyperplasia in in-stent restenosis lesions.

Comparison of long-term prognostic evaluation between pre-intervention thrombolysis and primary coronary intervention: a prospective randomized trial: five-year results of the IMPORTANT study.

BACKGROUND: Acute efficacy and long-term prognostic differences between ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (primary PCI) and those treated with pre-intervention thrombolysis combined with back-up of facilitated PCI has not been evaluated in Japanese patients. The purpose of the present study was therefore to evaluate the differences between treatment with primary PCI (primary-PCI group) and pre-treatment with tissue-type plasminogen activator (t-PA) combined with back-up of facilitated PCI (prior-t-PA group). METHODS AND RESULTS: One hundred and one patients with STEMI were randomly assigned to 2 groups. Patients in the prior-t-PA group were then divided into 2 further groups, the facilitated-PCI and prior-t-PA alone groups. The patency rate at initial angiography, left ventricular ejection fraction (LVEF) at 6 months, and the major adverse cardiac event (MACE)-free rate at 5 years were then compared between the groups. The patency rate and LVEF in the prior-t-PA group was significantly higher than in the primary-PCI group (69% vs 17% respectively, P<0.001; 61.6+/-9.5% vs 55.0+/-11.6%, respectively; P=0.01). The MACE-free rate in the prior-t-PA group, however, was lower than in the primary-PCI group (58.7% vs 80.9%; P=0.03). The MACE-free rate in the facilitated-PCI group was equal to that in the primary-PCI group (73.7% vs 80.9%; P=0.39), whereas the MACE-free rate in the prior-t-PA-alone group was significantly lower than in the primary-PCI group (48.1% vs 80.9%; P=0.01). CONCLUSIONS: Primary PCI is superior to pre-intervention thrombolysis for long-term prognosis. Moreover, facilitated PCI may be as effective as primary PCI in patients with STEMI.