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Objective Previous studies have described several prognostic factors for heart failure (HF); however, these results were derived from registries consisting of conventional age groups, which might not represent the increasingly aging society. The present study explored the prognostic factors for all-cause death in hospitalized patients with HF across different age categories using an acute HF registry that included relatively old patients. Methods From a total of 1,971 consecutive patients with HF, 1,136 patients were enrolled. We divided the patients into 4 groups (≤65, 66-75, 76-85, and >85 years old) to evaluate all-cause death and prognostic factors of all-cause death. Results During the mean follow-up period of 1,038 days, 445 patients (39.2%) had all-cause death. A Kaplan-Meier analysis demonstrated significantly higher incidence of all-cause death in the elderly groups than in the younger groups (log-rank p85 years old group. Conclusions Atrial fibrillation was a notable predictor of HF in young patients, whereas frailty and low-grade albuminemia were essential predictive factors of HF in elderly patients. With the increasing number of elderly patients with HF, comprehensive multidisciplinary treatment will be necessary.

Background Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. Methods We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. Results In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors’ prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR

Background Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055. Conclusions The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

Background: Because the effectiveness of strengthening guideline-based therapy (GBT) to prevent heart failure (HF) rehospitalization of chronic HF patients remains unclear, this study investigated the characteristics of HF patients in the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) acute cohort. Methods and Results: We studied 254 rehospitalized HF patients from the KUNIUMI Registry. Optimized GBT was defined as a Class I or IIa recommendation for chronic HF based on the guidelines of the Japanese Circulation Society. The primary endpoint was all-cause death or first HF rehospitalization after discharge. Outcomes tended to be more favorable for patients who had rather than had not received optimized GBT (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.57-1.19; P=0.27). Similarly, among New York Heart Association (NYHA) Class IV patients, outcomes tended to be more favorable for those who had rather than had not undergone optimized GBT (HR 0.73; 95% CI 0.47-1.12; P=0.15). Importantly, outcomes were significantly more favorable among NYHA Class IV patients aged

Recent reports have revealed that patients who experienced early rehospitalization for heart failure (HF) had worse prognoses in terms of all-cause and cardiovascular deaths as compared to those who did not. However, precipitating factors for early rehospitalization for HF remain unknown. In this study, we assessed the precipitating factors for early rehospitalization and their impact in patients with HF.We consecutively included 242 patients (mean age: 80.4 years, females: 46.3%) with a history of rehospitalization for HF. They were divided into 2 groups: the early rehospitalization group (71 patients who were readmitted within 3 months of discharge) and the late rehospitalization group (171 patients who were readmitted after more than 3 months following discharge). During the mean follow-up period of 1,144 days (range: 857-1,417 days), 121 patients (50.0%) died. Kaplan-Meier analysis revealed that patients in the early rehospitalization group had worse prognosis (all-cause death and cardiovascular death) than those in the late rehospitalization group (log-rank p0.001). As the major precipitating factor for rehospitalization, poor compliance with the doctor's instructions on fluid and physical activity restrictions (determined by the patients or their families admittance of non-compliance with the instructions given at the time of discharge) was higher in the early rehospitalization group than in the late rehospitalization group [poor compliance with fluid restriction: 19.7% vs. 7.6% (p = 0.006), poor compliance with physical activity restriction: 21.1% vs. 9.4% (p = 0.013)].We concluded that early hospital readmission in patients with HF was associated with higher mortality rates. Compared to late rehospitalization, precipitating factors for early rehospitalization were more strongly dependent on the self-care behaviors of the patients. A more effective approach, such as multidisciplinary intervention, is essential to prevent early hospital readmission and subsequent poor prognosis.

Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (p = 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practice Trial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025, https://jrct.niph.go.jp/latest-detail/jRCT2052190025 ).

Although a domestic trial in Japan revealed that Absorb bioresorbable vascular scaffold (BVS) has no inferiority to everolimus-eluting stent (EES) cohort in the primary endpoint of the target lesion failure at 12 months, the scaffold/stent thrombosis (ST) rates with the BVS at 24 months were higher than those with the EES (Absorb BVS 3.1% vs. EES 1.5%), the ST rate of 3.1% with Absorb BVS is not an acceptable level in Japan. A cause-of-ST analysis revealed that cases in which diagnostic imaging and ensuing post-dilatation had been performed appropriately had lower ST rates than those without such management (within 1 year: 1.37% vs. 7.69%, from 1 to 2 years: 0.00% vs. 8.33%). Therefore, a further evaluation was needed to confirm that the ST rate with the Absorb BVS would be reduced by a proper implementation procedure. Regulatory approval was given conditionally to initiate rigorous post-marketing data collection in order to ensure the proper use of this device in limited facilities. The One-year Use-Result Survey in Japan for the Absorb BVS revealed no instances of ST. This approach to reducing the premarket regulatory burden of clinical trials and enhancing the post-marketing commitments of medical device regulation is useful for expediting patient access to innovative medical devices.

In 2013, a drug-coated balloon catheter (DCB) (SeQuent Please) for the treatment of coronary in-stent restenosis (ISR) was approved in Japan. The pre-marketing Japan domestic NP001 study demonstrated better outcomes of the DCB (n = 138) compared to plain balloon angioplasty (n = 72). After the introduction to marketing, a post-marketing surveillance (PMS) (n = 396) was conducted to evaluate the safety and efficacy of the DCB in Japanese routine clinical practice. The aim of this paper was to assess differences between the pre-marketing NP001 study and the PMS. Compared to the NP001 study, more complex lesions were treated in the PMS (type B2/C: 69.0% vs 20.4%, total occlusion: 11.2% vs 0%, p

Although balloon angioplasty for femoropopliteal artery lesions has been associated with restenosis rates of up to 60% at 12 months, the mechanism of restenosis has not been fully evaluated. The aim of this study was to evaluate the relationship between the vascular features observed on optical frequency domain imaging (OFDI) before and after balloon angioplasty of femoropopliteal artery lesions, and restenosis at 6 months. This study was a prospective multicenter single arm study. OFDI was performed before and after balloon angioplasty and plaque characteristics and vascular features, along with de novo lesions, were assessed. The primary outcome was the presence or absence of restenosis 6 months after balloon angioplasty. Residual platelet reactivity was assessed according to VerifyNow platelet reactivity units (PRUs). The number of patients completing 6 months of follow-up was 47, of which 14 had developed restenosis. Maximum thickness of the dissection flap (odds ratio (OR) 2.71; 95% confidence interval [0.9–8.0]; p = 0.071) and lesion length were identified as risk factors for restenosis (OR 1.015; 95% confidence interval [0.001–0.029]; p = 0.039). The mean PRU at the time of treatment in patients with restenosis was significantly higher than in those without restenosis (286.3 ± 82.6 vs. 208.5 ± 03.6, p = 0.026). Long lesions and major dissection on OFDI after balloon angioplasty for femoropopliteal artery lesions increase restenosis at 6 months. In addition, high residual platelet reactivity at the time of EVT may also be a risk factor for restenosis. Clinical Trial Registration Number UMIN000021120.

Recent improvements of balloon aortic valvuloplasty (BAV) devices and procedures have provided improved outcomes, but it is not clear whether the multiple-inflation BAV technique is effective in patients with symptomatic severe aortic valve stenosis (AS). We conducted an analysis of the impact of multiple-inflation BAV (at least 6 times inflation) on the mean aortic valve area (AVA) and mean aortic valve pressure gradient (AV-PG) in patients with symptomatic severe aortic stenosis as compared with conventional BAV (from single to three times inflation). We identified two studies of multiple-inflation BAV with antegrade approach using Inoue-balloon catheter (425 patients) and four studies of conventional BAV (170 patients) with retrograde approach. Using a random intercept model, we found that multiple-inflation BAV significantly increased mean AVA (mean difference (MD) [95% indicates confidence interval (CI)] = 0.25 [0.16–0.34], P

Background Stent thrombosis (ST) is a rare but serious complication after deployment of a drug-eluting stent. The features of ST after implantation of an everolimus-eluting stent (EES) have not been fully elucidated. Methods A comprehensive survey of real-world adverse event reporting with conditions for approval under the Pharmaceuticals and Medical Devices Act identified 490 cases of ST with EES. A total of 370 patients with definite ST after EES implantation [287 with early (E)ST (within 30 days), 54 with late (L)ST (31–365 days), and 29 with very late (VL)ST (over 1 year)] were divided into an EST group and an LST/VLST group to compare the patients and lesions characteristics. Results The frequency of patients with hemodialysis and in-stent restenosis (ISR) lesions were significantly higher in the LST/VLST group than in the EST group (hemodialysis, 22.9% vs 2.7%, p = 0.0001; ISR lesions, 25.9% vs 9.4%, p = 0.0001). Characteristic demographic factors for LST/VLST versus EST identified by multivariable model were hemodialysis and ISR lesions (hemodialysis: odds ratio 7.348, 95% confidence interval 2.458–21.968, p = 0.0001; ISR lesions: odds ratio, 2.490, 95% confidence interval 1.100–5.638, p = 0.027). The in-hospital death rates from ST were not significantly different between the EST group and the LST/VLST group (EST, 15% vs LST/VLST, 21.7%, p = 0.147). Conclusions Patient-related and lesion-related characteristics were significantly different between EST and LST/VLST. Data collection from adverse event reporting could be a helpful strategy for evaluation of this serious but rare complication.

Intravascular optical coherence tomography is a high-resolution intracoronary imaging modality, providing a microscopic image of intravascular features. However, it has lower penetration depth than intravascular ultrasound. Recently, a second-generation optical frequency-domain imaging (OFDI) technique has been developed to provide greater penetration depth and faster pullback speed. However, there is little evidence supporting the efficacy of OFDI in patients with peripheral artery disease (PAD) undergoing endovascular treatment (EVT). We aimed to evaluate the ability of OFDI to visualize vessel walls from the superficial femoral artery (SFA) to the below-knee (BK) arteries, as well as the coronary arteries. This clinical trial is a single-center, single-arm, open-label study to be conducted in Japan. A total of 20 patients will be enrolled in this study. The primary endpoint is to obtain a clear image of the intravascular features of the SFA and BK arteries, specifically the visualization of ≥ 270° of the vessel lumen in ≥ 16 out of 21 cross sections. Obtaining clear images in ≥ 85% of cases will be regarded as confirmation of the ability of OFDI to visualize vessel walls from the SFA to the BK arteries. This is the first clinical trial to be conducted accordance with good clinical practice to expand the indications of OFDI for PAD patients undergoing EVT in Japan. The result of this study will help provide another imaging option during EVT in daily practice.

Objectives: Balloon angioplasty for in-stent restenosis (ISR) in the superficial femoral artery (SFA) has a high recurrent restenosis rate; however, its mechanism has not been fully and precisely evaluated using high-resolution intravascular imaging. Thus, we aimed to evaluate the relationship between vascular features obtained by optical frequency domain imaging (OFDI) and recurrent restenosis at 6 months. Methods: This was a prospective multicenter single-arm study. OFDI was performed before and after balloon angioplasty, and vascular features were assessed. A multi-layered ISR pattern detected by OFDI was defined as several signal-poor appearances with a high-signal band adjacent to the luminal surface. The primary outcome was defined as recurrent restenosis 6 months after balloon angioplasty. Results: Given that this study was terminated early, only 18 patients completed the 6-month follow-up; of these, 8 developed restenosis. Recurrent restenosis at 6 months tended to be related to a multi-layered ISR pattern (odds ratio (OR), 6.67; 95% confidence interval (CI), 0.81-54.96; p=0.078) and the minimum lumen area (MLA) after balloon angioplasty (OR, 0.71; 95%CI, 0.48-1.04; p=0.077). Conclusion: A multi-layered ISR pattern and MLA after balloon angioplasty detected by OFDI might be risk factors for recurrent ISR in the SFA.

Background The impact of reduction in glycemic excursion on coronary plaques remains unknown. This study aimed to elucidate whether a dipeptidyl peptidase 4 inhibitor could reduce the glycemic excursion and stabilize the coronary plaques compared with conventional management in coronary artery disease (CAD) patients with impaired glucose tolerance (IGT). Methods This was a multicenter, randomized controlled trial including CAD patients with IGT under lipid-lowering therapy receiving either vildagliptin (50 mg once a day) or no medication (control group) regarding glycemic treatment. The primary endpoint was changes in the minimum fibrous cap thickness and lipid arc in non-significant native coronary plaques detected by optical coherence tomography at 6 months after intervention. Glycemic variability expressed as the mean amplitude of glycemic excursion (MAGE) measured with a continuous glucose monitoring system was evaluated before and 6 months after intervention. Results A total of 20 participants with 47 lesions were allocated to either the vildagliptin group (10 participants, 22 lesions) or the control group (10 participants, 25 lesions). The adjusted difference of mean changes between the groups was − 18.8 mg/dl (95% confidence interval, − 30.8 to − 6.8) (p = 0.0064) for the MAGE (vildagliptin, − 20.1 ± 18.0 mg/dl vs. control, 2.6 ± 12.7 mg/dl), − 22.8° (− 40.6° to − 5.1°) (p = 0.0012) for the mean lipid arc (vildagliptin, − 9.0° ± 25.5° vs. control, 15.8° ± 16.8°), and 42.7 μm (15.3 to 70.1 μm) (p = 0.0022) for the minimum fibrous cap thickness (vildagliptin, 35.7 ± 50.8 μm vs. control, − 15.1 ± 25.2 μm). Conclusions Vildagliptin could reduce the MAGE at 6 months and may be associated with the decreased lipid arc and increased minimum FCT of the coronary plaques in CAD patients with IGT as compared with the control group. These findings may represent its potential stabilization effect on coronary plaques, which are characteristic in this patient subset. Trial registration Registered in the UMIN clinical trial registry (UMIN000008620), Name of the registry: VOGUE trial, Date of registration: Aug 6, 2012, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000010058

International audience; Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting. (C) 2020 by the American College of Cardiology Foundation.

Background Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports used for safety measures after approval.Methods and Results:Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio [OR]: 4.76, 95% confidence interval [CI]: 3.26-6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61-5.14), hemodialysis (OR: 2.69, 95% CI: 1.66-4.36), prior stroke (OR: 2.28, 95% CI: 1.15-4.51), over 70 years old (OR: 1.62, 95% CI: 1.22-2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27-0.63) were independent factors for in-hospital death after DES-ST. Conclusions LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.

Although balloon angioplasty for femoropopliteal artery lesions has been associated with restenosis rates of up to 60% at 12 months, the mechanism of restenosis has not been fully evaluated. The aim of this study was to evaluate the relationship between the vascular features observed on optical frequency domain imaging (OFDI) before and after balloon angioplasty of femoropopliteal artery lesions, and restenosis at 6 months. This study was a prospective multicenter single arm study. OFDI was performed before and after balloon angioplasty and plaque characteristics and vascular features, along with de novo lesions, were assessed. The primary outcome was the presence or absence of restenosis 6 months after balloon angioplasty. Residual platelet reactivity was assessed according to VerifyNow platelet reactivity units (PRUs). The number of patients completing 6 months of follow-up was 47, of which 14 had developed restenosis. Maximum thickness of the dissection flap (odds ratio (OR) 2.71; 95% confidence interval [0.9-8.0]; p = 0.071) and lesion length were identified as risk factors for restenosis (OR 1.015; 95% confidence interval [0.001-0.029]; p = 0.039). The mean PRU at the time of treatment in patients with restenosis was significantly higher than in those without restenosis (286.3 ± 82.6 vs. 208.5 ± 03.6, p = 0.026). Long lesions and major dissection on OFDI after balloon angioplasty for femoropopliteal artery lesions increase restenosis at 6 months. In addition, high residual platelet reactivity at the time of EVT may also be a risk factor for restenosis.Clinical Trial Registration Number UMIN000021120.

Background Although a prospective randomized control study revealed that 3-month dual anti-platelet therapy (DAPT) is safe and does not compromise the efficacy of everolimus-eluting stent (EES) in selected patients, detailed vessel healing at early phase after EES implantation has yet to be investigated in Japanese patients. Methods and results A total of 27 lesions in 19 patients treated with EES were serially evaluated by using optical coherence tomography (OCT) at 3, 6, and 12 months after stent implantation. In addition to standard quantitative OCT parameters, the percentage of stents with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (63 ± 17 μm; 83 ± 30 μm; and 111 ± 44 μm, respectively; p = 0.006) and small decrease in average lumen area (6.80 ± 2.57 mm2, 6.62 ± 2.58 mm2, 6.33 ± 2.58 mm2, p = 0.038) from the 3- to the 12-month follow-up. The incidences of uncovered and malapposed struts were low at 3 months and did not significantly change at 6 months and 12 months (3.01 ± 4.43; 2.45 ± 3.75; and 1.47 ± 3.16, p = 0.143, and 0.75 ± 0.65; 0.63 ± 0.73; and 0.58 ± 1.42, p = 0.162, respectively). Also, frequency of struts with PLIA was already low at three months and significantly decreased during the follow-up (6.4 ± 6.5; 4.6 ± 5.4; and 2.3 ± 3.3, respectively; p = 0.001). Conclusion Favorable vessel healing was achieved at 3 months after EES implantation without neointimal hyperplasia which was persistently suppressed up to 12 months.

Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.

A prospective randomized clinical trial showed that the BioFreedom stent (Biosensors International), which is a polymer-free and carrier-free drug-coated stent, was significantly superior to a bare-metal stent (BMS) in patients at high bleeding risk who were receiving a 1-month course of dual antiplatelet therapy (DAPT). However, the stent thrombosis rate (2.01% for BioFreedom vs. 2.20% for BMS) was 4-6-fold higher than that of approved drug-eluting stents based on real-world data in Japan. Furthermore, the frequency of stent thrombosis at more than 1 month with the BioFreedom stent was slightly higher than that at less than 1 month. This result suggested that it would not be acceptable to stop DAPT universally at 1 month. Thus, the target patients for the BioFreedom stent are unspecified patients at high bleeding risk needing to continue DAPT for as long as necessary in Japan. Therefore, based on the pre- and post-marketing balance of medical devices regulations, regulatory approval was given for unspecified patients conditionally upon real-world data collection of 2,000 patients with a Use-Results Survey, instead of conducting additional pre-marketing clinical trial(s). The Use-Results Survey System is part of a strategy to expedite patients' access to innovative medical devices and to accelerate the development of medical devices.

Background Previous studies have suggested that peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) is associated with adverse short- and long-term outcomes, and several morphological predictors of PMI have been studied. However, the determinants of PMI under novel anti-platelet therapy are not fully elucidated. Methods and results PRASFIT-Elective is a multicenter, parallel-group study of PCI patients in non-acute settings receiving either prasugrel or clopidogrel in addition to aspirin. Among 742 study patients, 94 (116 lesions) underwent optical coherence tomography (OCT) to evaluate the area of intra-stent tissue (IST, which comprises tissue protrusion and thrombus) after stenting in addition to standard parameters. We investigated the relationship between the peak creatine kinase (CK)-MB fraction levels after PCI and post-stent OCT findings, as well as on-treatment platelet reactivity determined by the P2Y12 reaction units (PRU) at PCI, in a post hoc manner. The multivariate linear analysis revealed that a larger total IST area (standardized coefficient: 0.370, p Conclusion Following elective PCI, a large IST area originating from a lipid-rich plaque and a smaller minimal stent diameter were associated with PMI.

Aims Although pathological studies have indicated the development of neoatherosclerosis (NA) after stenting, its risk factors and impact on future clinical events remain unclear. We aimed to clarify the possible risk factors for NA development and to evaluate the impact of NA in a large Japanese observational OCT database of patients with coronary heart disease. Methods and results One hundred and seventy-five consecutive patients (314 lesions) who underwent OCT examination >1 year after bare metal or drug-eluting stent implantation were enrolled. We assessed the presence of NA by follow-up OCT and compared adverse clinical events between NA+ and NA- patients. Forty-six patients had NA at the follow-up OCT. These patients had higher low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) levels at follow-up. In multivariate logistic analysis, LDL cholesterol and CRP levels at follow-up were independently associated with the presence of NA (odds ratio [OR]: 1.022, p=0.008, OR 1.022, p=0.001, respectively). Moreover, patients with NA had a higher incidence of major adverse cardiac events (MACE) at follow-up. Multivariate Cox hazard analysis showed that the presence of NA was an independent risk factor for MACE (hazard ratio: 2.909, p=0.012). Conclusions High LDL cholesterol and CRP levels may be risk factors for NA development in patients treated with coronary stents. Moreover, the presence of NA was independently associated with MACE, suggesting the need for careful clinical follow-up of these patients.

Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention–related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

The indication for MitraClip (Abbott Vascular, Santa Clara, CA, USA) in the USA is degenerative mitral regurgitation (DMR), but the Japanese indication includes both DMR and functional mitral regurgitation (FMR), in patients without severe left ventricular dysfunction. One of the reasons for this difference is that the Japanese Circulation Society submitted a formal request to the Japanese government for early approval of MitraClip for both DMR and FMR on the basis of unmet medical need for MR patients resistant to medical therapy, but at prohibitive risk for mitral valve surgery. Here, we describe the regulatory approval review process of MitraClip in Japan. Clinical data from outside Japan indicated that MitraClip provides significant improvements from baseline in New York Heart Association Class and hospitalizations for heart failure due to the reduction of MR grade without adversely affecting long-term prognosis in FMR patients as well as DMR patients. Also, a Japanese domestic trial showed a favorable acute procedural success rate without serious adverse events with MitraClip in both DMR and FMR patients. Further, it is considered in Japan that improvement of MR mechanically is clinically important in both DMR and FMR, in patients without severe left ventricular dysfunction. On the basis of these considerations, the MitraClip was approved in Japan for indications of both DMR and FMR with preserved cardiac function in patients at prohibitive risk for mitral valve surgery.

Background: Clinical efficacy of balloon pulmonary angioplasty (BPA) to the patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) for improving pulmonary hemodynamics and exercise tolerance has been reported in these several years. However, reperfusion pulmonary injury (RPI) remains to be a major complication of BPA to overcome. This study elucidated the local predictor of RPI. Methods: Twenty-eight consecutive patients with non-operable CTEPH underwent BPA for lesions in the segmental or sub-segmental vessels. Pre- and post-BPA pulmonary arterial pressures at proximal (Pp) and distal (Pd) to the stenosis were measured by a 0.014-in. pressure wire. Positive or negative RPI was evaluated by chest computed tomography in each re-perfused segment separately 4 h after BPA. Results: Pressure measurements pre- and post-BPA were obtained from 110 lesions, where Pd and pressure ratio (Pd/Pp) increased after BPA in all lesions. Among them, RPI was observed in 49 lesions (44.5%). In the RPI-positive lesions, post-BPA Pd and post-BPA Pd/Pp were higher compared with the RPI-negative lesions. Multivariate logistic analysis revealed that the post-BPA Pd was independently associated with RPI incidence. Receiver operating characteristic curve analysis demonstrated the best cut-off value of 19.5 mm Hg for post-BPA Pd to predict RPI. Conclusions: High reperfusion pressure after BPA could be a predictor of RPI. Monitoring local pressure during BPA procedure may have a potential to reduce the incidence of RPI.

In the original publication of the article, the author group was published without full names and one of the co-authors' name was published incorrectly. The full names of author group and correct co-authors' name are given in this Correction.

Platelet reactivity in the presence of clopidogrel is deteriorated in patients undergoing hemodialysis (HD). However, the impact of residual platelet reactivity with prasugrel use in Japanese patients on HD remains unclear. This was a prospective, multi-center, single-arm study conducted to compare platelet reactivity of prasugrel 3.75 mg per day vs. clopidogrel 75 mg per day in patients on chronic HD. We assessed P2Y12 reaction units (PRU) using the VerifyNow® P2Y12 test for all enrolled patients at baseline (clopidogrel treatment) and at 14 days (prasugrel treatment) pre- and post-HD. Clinical outcomes data were obtained on day 14. A total of 38 patients on HD were included in this study. The PRU were significantly higher in patients on clopidogrel than in patients on prasugrel in both phases (pre-HD: clopidogrel 226 ± 80 vs. prasugrel 175 ± 82, p

Background The Nobori (Terumo Corporation, Tokyo, Japan) is a biolimus A9-eluting stent (BES) featured with a biodegradable polymer coated on the abluminal side only. We previously reported that favourable vessel healing was achieved at 6-12 months after BES implantation. However, detailed long-term vessel reaction after BES deployment is unclear. Methods Twenty-two BESs were serially evaluated using optical coherence tomography (OCT) at 6, 12, and 24 months after stenting. Average neointimal thickness, uncovered struts, and neointimal unevenness score (each cross-section as maximum neointimal thickness in 1 cross section divided by the average neointimal thickness of the same cross-section) were manually measured. In addition, we evaluated the percentage of struts with peri-strut low-intensity area (a region around stent struts that homogenously showed less intensity than the surrounding tissue, which suggests fibrin deposition or impaired neointima maturation), thrombi, and atherogenic neointimas (neointimas containing a diffuse border and poor-signal region with invisible struts due to marked signal attenuation). Results Serial OCT observation revealed a small gradual increase in neointimal thickness from 6 to 24 months (73 ± 24 μm; 81 ± 26 μm; and 108 ± 35 μm, respectively, P = 0.001) with a nonsignificant decrease in the lumen area (6.36 ± 1.98 mm 2 ; 6.18 ± 2.04 mm 2 ; and 5.87 ± 2.06 mm 2 ; P = 0.72). Frequency of uncovered struts (3.89 ± 3.91%; 1.55 ± 1.63%; and 0.23 ± 0.67%; P = 0.001), neointimal unevenness score (1.95 ± 0.18% to 1.86 ± 0.19% to 1.78 ± 0.17; P = 0.012), percentage of thrombi (5%, 0%, and 0%; P = 0.37) and peri-strut low-intensity area (6.8%, 5.1%, and 1.6%; P = 0.017) decreased from 6 to 12 and 24 months. Atherogenic neointima was not observed in the event-free OCT cohort. Conclusions The Nobori stent achieved acceptable long-term vessel healing, mostly without adverse vessel reactions.

Objectives This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy. Background There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD. Methods This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was Results In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p Conclusions Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients.

In Japan, a recent issue that required an urgent response was the streamlining of regulations concerning clinical trials of medical devices. On July 31, 2017, the Ministry of Health, Labour and Welfare enacted a new regulatory framework called the fast-break scheme for innovative medical devices aiming to expedite patient access while reducing the premarket regulatory burden of clinical trials and enhancing postmarketing commitments. The new framework is expected to provide greater benefits to patients who require access to new medical devices and to companies via improved transparency and predictability, as well as to reduce the social and medical cost incurred for medical innovation.

Background Although drug-eluting stents have significantly reduced the midterm incidence of target lesion revascularization (TLR), in vivo studies on long-term vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) are limited. The aim of this study was to compare long-term arterial healing with SESs and PESs. Methods We evaluated 27 SESs (23 patients) and 21 PESs (20 patients) by serial optical coherence tomography at 6 months (midphase) and ≥ 3 years (late phase) after stenting and evaluated the change of neointimal thickness (NIT), the percentages of uncovered and malapposed struts, peristrut low-intensity area (region around stent struts with a homogeneously lower intensity appearance than surrounding tissue), thrombus, and atherogenic neointima. Results At follow-up, most SESs showed a progressive increase in the average NIT, whereas PESs showed variable changes. Between midphase and late phase, NIT increased significantly in SESs (midphase, 94.1 ± 49.3; late phase, 130.2 ± 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4 ± 122.9; late phase, 136.0 ± 77.7; P = 0.04). The percentages of uncovered struts decreased significantly in SESs; conversely, variable changes were observed in PESs. Peristrut low-intensity area and thrombus formation decreased in SESs but remained largely unchanged in PESs. The prevalence of atherogenic neointima was greater in the late phase than in the midphase in both groups but was similar for both stents. Conclusions Long-term vessel healing was different for SESs and PESs. Progressive vessel healing was consistently observed in SESs, whereas a heterogeneous process of delayed vessel healing was noted for PESs.

Background: Although both optical coherence tomography (OCT) and angioscopy are robust tools for detecting intrastent thrombi and neoatherosclerosis in vivo, whether OCT findings are comparable with angioscopy findings remains unclear. Methods and Results: 22 patients presenting with de novo lesions underwent 26 sirolimus-eluting stent (SES) implantations, with follow-up OCT and angioscopy at 10 months post-implantation for segmental assessment of the proximal, mid-, and distal SES segments (66 segments). The mean signal intensity index (signal intensity of the neointima/signal intensity of fibrous intimal hyperplasia) was quantified for angioscopically detected in-stent yellow and white segments. The detection rate for red thrombi was numerically higher with angioscopy than with OCT (17% vs. 9%; P=0.053). Angioscopically detected in-stent yellow segments were categorized into 3 OCT patterns: “high-attenuation tissue covering struts” (OCT-defined neoatherosclerosis), “high-attenuation tissue underneath struts,” and “low-attenuation and low-intensity tissue covering struts”; further, macrophage-like appearance was most frequently observed with OCT-defined neoatherosclerosis (56%, 6.3%, and 0%, respectively, P

Background:Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM).Methods and Results:We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients.Conclusions:Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients. (Circ J2014;78:2188–2196)

Background The impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms. Methods This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100 mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (*1/*2, *1/*3, *2/*2, *3/*3, *2/*3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT. Results Of the 112 Japanese patients, 75 were LOF carriers (67.0%). The patients were divided into tertiles according to the PON1 activity (tertile 1; 283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus. Conclusion Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.

Background: We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses. Methods and Results: One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before – after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P

A 65-year-old man was referred to our hospital due to an acute onset of dyspnea and persistent fever. Echocardiography revealed an ejection fraction (EF) of 25% with diffuse severe left ventricular (LV) dysfunction. 18F-fluorodeoxy glucose-positron emission tomography imaging showed significantly increased uptake by the LV and right ventricular walls, indicating active inflammation. The histologic findings of the endomyocardial biopsy specimens indicated the presence of epithelioid cell granuloma. The final diagnosis was thus cardiac sarcoidosis with acute inflammation. Five-months after the initiation of steroid therapy, echocardiography showed an EF of 50%. This is a rare case in which acute inflammation led to acute heart failure mimicking acute myocarditis.

The Japanese government recently enacted regulations that set up an adaptive framework for the approval of regenerative medical products under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act) (Konomi et al., 2015). Here, we report on the review process for the first two approved products and discuss key differences.

Background Hemodialysis (HD) patients are at high risk for adverse clinical outcomes after drug-eluting stent (DES) implantation. However, the impact of residual platelet reactivity under dual anti-platelet therapy in this subset of patients remains unclear. Methods We enrolled 142 stable angina patients (194 lesions) treated with DES, who were taking aspirin and 75 mg clopidogrel and had undergone 8-month angiography with optical coherence tomography (OCT). OCT findings and major adverse cardiac events (MACEs) at 1 year (cardiac death, acute coronary syndrome, target lesion and vessel revascularization, and stent thrombosis) were compared between 28 HD patients and 114 non-HD patients. Responsiveness to clopidogrel was assessed by measuring P2Y12 reaction unit (PRU) at 8 months. Results PRU was significantly higher in HD patients than in non-HD patients (p = 0.006), even though proportion of cytochrome P450 2C19 genotype was equivalent. HD patients had a significantly higher rate of thrombi formation (assessed using OCT) and MACEs than non-HD patients (thrombi: p = 0.001; MACEs: p = 0.0001). The PRU value was independently associated with MACEs in both groups. The optimal cutoff values of PRU for predicting MACEs were 235 for HD patients and 259 for non-HD patients. Conclusions HD was associated with a high residual platelet reactivity, which may contribute to the higher incidence of MACEs after DES implantation in HD patients. HD may be a patient profile that merits a more potent anti-platelet regimen.

Adverse plaque characteristics (APCs) by coronary computed tomography (CT) angiography (CTA) are associated with myocardial ischaemia and future acute coronary syndromes. The overall objective was to determine whether APCs on non-invasive CTA are associated with vulnerable plaque features by invasive optical coherence tomography (OCT).Sixty-eight coronary plaques in 45 patients were evaluated by CTA and OCT. APCs by CTA were: positive remodelling (PR), remodelling index ≥1.10; low attenuation plaque (LAP), any intraplaque voxel30 Hounsfield units; spotty calcification (SC), intraplaque calcification ≤3 mm; and 'napkin-ring' sign, low intraplaque attenuation surrounded by a higher attenuation rim. OCT evaluated plaques for thin-cap fibroatheroma (TCFA, ≤65 µm, lipid arch90°) and macrophage infiltration. Increasing plaque vulnerability was graded by OCT as having no TCFA, TCFA without macrophage infiltration, and TCFA with macrophage infiltration. OCT lesions included those with no TCFA (n = 44), TCFA without macrophage infiltration (n = 7), and TCFA with macrophage infiltration (n = 17). Increasing plaque vulnerability grade by OCT was associated with higher diameter stenosis (43.6 vs. 40.7 vs. 57.3%, P = 0.01), and greater prevalence of PR (11 vs. 43 vs. 71%, P0.001), LAP (11 vs. 29 vs. 59%, P = 0.001), and SC (2 vs. 29 vs. 18%, P = 0.02), but not for napkin-ring sign (P = 0.18). In multivariable analysis, PR [odds ratio (OR) 16.9, 95% confidence interval (CI) 3.9-73.3, P0.001] and LAP (OR 11.2, 95% CI 2.8-44.3, P = 0.001) predicted TCFA with macrophage infiltration, whereas SC and napkin-ring sign did not.Plaques demonstrating PR and LAP by CTA are associated with TCFA with macrophage infiltration by OCT.

This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy.There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD.This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was120 mg/dl under statin treatment or100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated.In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient β = 0.080 ± 0.020 [standard error], p0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007).Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients.

Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM). METHODS AND RESULTS: We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients.Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients.

Background:Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6–9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear.Methods and Results:We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72±23 to 82±25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96±3.97% to 1.51±1.63%, P=0.001, and 0.50±1.84% to 0.06±0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24).Conclusions:Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months. (Circ J 2014; 78: 1882–1890)