One-year safety and effectiveness of the Agent paclitaxel-coated balloon for the treatment of small vessel disease and in-stent restenosis.

The Agent device consists of a semi-compliant balloon catheter, which is coated with a therapeutic low-dose formulation of paclitaxel (2 µg/mm2) blended with an inactive excipient acetyl-tri-n-butyl citrate (ATBC). AGENT Japan SV is a randomized controlled study that enrolled 150 patients from 14 Japanese sites treated with Agent or SeQuent Please paclitaxel-coated balloon. This study also includes a single-arm substudy evaluating the safety and effectiveness of Agent in patients with in-stent restenosis (ISR). Patients with a single de novo native lesion (lesion length ≤ 28 mm and reference diameter ≥ 2.00 to < 3.00 mm) were randomized 2:1 to receive either Agent (n = 101) or SeQuent Please (n = 49). The ISR substudy enrolled 30 patients with lesion length ≤ 28 mm and reference diameter ≥ 2.00 to ≤ 4.00 mm. In the SV RCT, target lesion failure (TLF) at 1 year occurred in four patients treated with Agent (4.0%) versus one patient with SeQuent Please (2.0%; P = 1.00). None of the patients in either treatment arm died. There were no significant differences in the rates of myocardial infarction, target lesion revascularization and target lesion thrombosis through 1 year. In the ISR substudy, the 1-year rates of TLF and target lesion thrombosis were 6.7% and 0.0%, respectively. These data support the safety and effectiveness of the Agent paclitaxel-coated balloon in patients with small vessels and ISR.

Intravascular Lithotripsy for Vessel Preparation in Calcified Coronary Arteries Prior to Stent Placement　- Japanese Disrupt CAD IV Study 2-Year Results.

Background: Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcification to enhance vessel compliance and optimize stent deployment. The Disrupt CAD IV study enrolled patients with severe coronary artery calcification. The primary safety (30-day major adverse coronary events [MACE], 6.3%) and effectiveness (procedural success, 93.8%) endpoints were achieved. The present analysis evaluated the 2-year outcomes of the study. Methods and Results: Disrupt CAD IV (NCT04151628) was a prospective, single-arm, multicenter study designed for regulatory approval of the Shockwave Coronary C2 IVL system in Japan. Angiographic outcomes were analyzed by an independent core laboratory and adverse events were adjudicated by a Clinical Events Committee. Kaplan-Meier analysis was performed for MACE (composite of cardiac death, MI or target-vessel revascularization [TVR]), target lesion failure (TLF: composite of cardiac death, TV-MI, and target lesion revascularization [TLR]), and stent thrombosis (ST). At 2 years, 62 subjects had completed follow-up. MACE occurred in 12.6% (cardiac death 0.0%, MI 6.3%, TVR 7.9%) and TLF occurred in 7.8% of patients, with both rates driven by non-Q-wave MI events (6.3%). TLR was 3.2%; no ST occurred through 2 years. Conclusions: Treatment with IVL in patients with severely calcified coronary lesions was associated with low rates of MACE, TLR, and ST at 2 years, demonstrating continued durable safety and effectiveness of coronary IVL in a Japanese population.

First randomised controlled trial comparing the sirolimus-eluting bioadaptor with the zotarolimus-eluting drug-eluting stent in patients with de novo coronary artery lesions: 12-month clinical and imaging data from the multi-centre, international, BIODAPTOR-RCT.

Background: The DynamX™ bioadaptor is the first coronary implant technology with a unique mechanism of unlocking the bioadaptor frame after polymer resorption over 6 months, uncaging the vessel while maintaining a dynamic support to the vessel. It aims to achieve the acute performance of drug-eluting stents (DES) with the advantages of restoration of vessel function. Methods: This international, single blinded, randomised controlled (1:1) trial compared a sirolimus-eluting bioadaptor with a contemporary zotarolimus-eluting stent (DES) in 34 hospitals in Europe, Japan and New Zealand. Patients with de novo coronary lesions and absence of acute myocardial infarction were enrolled from January 2021 to Feburary 2022. The implantation of the bioadaptor followed the standards of DES. An imaging subset of 100 patients had angiographic and intravascular ultrasound assessments, and 20 patients additionally optical coherence tomography. Data collection will continue through 5 years, we herein report 12-month data based on an intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT04192747). Findings: 445 patients were randomised between January 2021 and February 2022. Device, lesion and procedural success rates, and acute gain were similar amongst the groups. The primary endpoint, 12-month target lesion failure, was 1.8% [95% CI: 0.5; 4.6] (n = 4) versus 2.8% [95% CI: 1.0; 6.0] (n = 6), pnon-inferiority < 0.001 for the bioadaptor and the DES, respectively (Δ-1.0% [95% CI: -3.3; 1.4]). One definite or probable device thrombosis occurred in each group. The 12-month imaging endpoints showed superior effectiveness of the bioadaptor such as in-device late lumen loss (0.09 mm [SD 0.34] versus 0.25 mm [SD 0.39], p = 0.04), and restored compliance and cyclic pulsatility (%mid in-device lumen area change of 7.5% versus 2.7%, p < 0.001). Interpretation: This is the first randomised controlled trial comparing the novel bioadaptor technology against a contemporary DES. The bioadaptor demonstrated similar acute performance and 12-month clinical outcomes, and superior imaging endpoints including restoration of vessel function. Funding: The study was funded by Elixir Medical.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Drug-Coated Balloon for the Treatment of Small Vessel Coronary Artery Disease　- A Randomized Non-Inferiority Trial.

BACKGROUND: Drug-coated balloons (DCB) have shown promising results for the treatment of in-stent restenosis (ISR) and small vessel disease (SVD). However, data comparing the treatment efficacy of different DCBs are limited.Methods and Results: AGENT Japan is a prospective randomized controlled trial that compares the Agent balloon coated with a low-dose formulation of paclitaxel (2 µg/mm2) to the SeQuent Please paclitaxel-coated balloon (3 µg/mm2) for the treatment of SVD. Patients with target lesion length ≤28 mm and reference diameter between ≥2.00 and <3.00 mm were randomized 2 : 1 for treatment with Agent (n=101) or SeQuent Please (n=49). This trial also includes a separate single-arm substudy evaluating the clinical safety and effectiveness of Agent in patients with ISR. The primary endpoint of 6-month target lesion failure (TLF) was observed in 3.0% of Agent and 0.0% of SeQuent Please patients (difference=3.0%; 97.5% upper confidence bound [UCB]=9.57%, which is less than the prespecified margin of 13.2%; Pnon-inferiority=0.0012). There were no deaths or thrombosis, and angiographic and quality-of-life outcomes were comparable between groups. The AGENT Japan ISR substudy (n=30) primary endpoint was met because the one-sided 97.5% UCB for 6-month TLF (3.3%) was significantly less than the study success criterion of 15.1% (97.5% UCB=9.8%; P<0.0001). CONCLUSIONS: Data from this study demonstrate good clinical outcomes with the Agent DCB when used to treat patients with SVD or ISR.

Long-term outcome and risk factors associated with events in patients with atrial fibrillation treated with oral anticoagulants: The ASSAF-K registry.

BACKGROUND: Oral anticoagulant therapy for atrial fibrillation (AF) has changed dramatically. Direct oral anticoagulant (DOAC) therapy is administered by general practitioners and specialists. However, the beneficial long-term effects and safety of DOACs have not been well investigated in real-world clinical practice. METHODS: The ASSAF-K (a study of the safety and efficacy of OAC therapy in the treatment of AF in Kanagawa), a prospective, multi-center, observational study, was conducted to clarify patient characteristics, status of OAC treatment, long-term outcomes, and adverse events, including cerebrovascular disease, bleeding, and death. RESULTS: A total of 4014 patients were enrolled (hospital: 2500 cases; clinic: 1514 cases). The number of patients in the final dataset was 3367 (mean age, 72.6 ±â€¯10.0 years; males, 66.3 %). CHA2DS2-VASc and HAS-BLED scores were 3.0 ±â€¯1.6 and 2.2 ±â€¯1.0, respectively. The risk factors of the primary composite outcome (all-cause death, serious bleeding events, cerebral hemorrhage, and stroke) were higher age, lower body mass index, lower diastolic blood pressure, lower creatine clearance, history of heart failure, history of stroke, and medication of anti-platelet agents. The event-free rates of the primary composite outcome with DOACs, warfarin, and without OACs were 92.7 %, 88.0 %, and 87.4 %, respectively. The event rate of DOACs was significantly lower than that of warfarin [HR 0.63 (95 % CI 0.48-0.81)], and similar results were observed after adjustment for AF stroke risk score [HR 0.70 (95 % CI 0.54-0.90)]. Serious bleeding events tended to occur less frequently with DOACs compared with warfarin [unadjusted HR 0.53 (95 % CI 0.31-0.91), adjusted HR 0.61 (95 % CI 0.33-1.11)]. CONCLUSIONS: This multi-center registry demonstrated the long-term outcome in patients with AF treated with and without OACs and suggests that DOAC therapy is safe and beneficial in hospitals and clinics.

Radial versus femoral access in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: A propensity-matched analysis from real-world data of the K-ACTIVE registry.

BACKGROUND: The access site for primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) recently shifted from femoral to radial. However, few real-world data on Japanese patients exist. METHODS: To elucidate the clinical selection and impact of the access site in STEMI patients, we analyzed a Japanese observational prospective multicenter registry of acute myocardial infarction (K-ACTIVE: Kanagawa ACuTe cardIoVascular rEgistry) in 2015 to 2021. Data were analyzed in the entire population and a propensity score-matched population adjusted for confounding factors. Major adverse cardiac event (MACE) was defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Bleeding Academic Research Consortium (BARC) type 3 or 5 was used to assess bleeding events. MACE plus BARC type 3 or 5 bleeding were considered composite events. Clinical outcomes were followed for 30 days. RESULTS: The 6802 STEMI patients included 4786 patients with radial access (70.3 %) and 2016 with femoral access (29.7 %). Femoral access tended to be selected for more severe conditions than radial access. The median door-to-device time in the radial access group was significantly shorter than the femoral access group in the entire population (75 min versus 79 min, p < 0.01). After propensity score matching (each group, n = 1208), the incidence of MACE tended to be lower in the radial access group [risk ratio (RR) 0.83, 95 % confidence interval (CI) 0.63-1.09, p = 0.17]. The incidence of BARC 3 or 5 bleeding was significantly less in the radial access group (RR 0.47, 95%CI 0.23-0.97, p = 0.04). The incidence of composite events was significantly less in the radial access group (RR 0.74, 95%CI 0.57-0.96, p = 0.02). CONCLUSION: In STEMI patients undergoing primary PCI, in comparison to femoral access, radial access reduced composite events in the entire population and the matched population, through a reduction in MACE and BARC 3 or 5 bleeding.

Intravascular Lithotripsy for Vessel Preparation in Calcified Coronary Arteries Prior to Stent Placement　- Japanese Disrupt CAD IV Study 1-Year Results.

Background: Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhance vessel compliance, and optimize stent deployment. The Disrupt CAD IV study enrolled patients with severe coronary artery calcification and demonstrated low 30-day major adverse cardiovascular events (MACE) and high procedural success following IVL with no final serious angiographic complications. To date, long-term outcomes have not been reported. This analysis evaluates 1-year outcomes of Disrupt CAD IV. Methods and Results: Disrupt CAD IV was a prospective single-arm multicenter study of IVL performed in a Japanese population with severe coronary artery calcification. Main outcomes included MACE (a composite of cardiac death, myocardial infarction [MI], or target vessel revascularization [TVR]), and target lesion failure (TLF; a composite of cardiac death, target vessel MI, and target lesion revascularization [TLR]) at 1 year. Compliance with patient follow-up at 1 year was 100%. MACE occurred in 9.4% of patients (cardiac death 0.0%, MI 6.3%, TVR 4.7%) and TLF occurred in 6.3% of patients, with both rates driven by non-Q wave MIs (6.3%). The TLR rate at 1 year was 1.6% and no stent thrombosis events were reported. Conclusions: Treatment of severely calcified coronary lesions with IVL was associated with low rates of 1-year MACE and TLR, suggesting durable safety and effectiveness of IVL-facilitated coronary stent implantation in severely calcified lesions in a Japanese population.

Rationale and design of the TACTICS registry: Optical coherence tomography guided primary percutaneous coronary intervention for patients with acute coronary syndrome.

BACKGROUND: Recent retrospective investigations have suggested that optical coherence tomography (OCT) enables the diagnosis of underlying acute coronary syndrome (ACS) causes such as plaque rupture, plaque erosion, and calcified nodule. The relationships of these etiologies with clinical outcomes, and the clinical utility of OCT-guided primary percutaneous coronary intervention (PCI) are not systematically studied in real-world ACS treatment settings. METHODS: The TACTICS registry is an investigator-initiated, prospective, multicenter, observational study to be conducted at 21 hospitals in Japan. A total of 700 patients with ACS (symptom onset within 24 h) undergoing OCT-guided primary PCI will be enrolled. The primary endpoint of the study is to identify the underlying causes of ACS using OCT-defined morphological assessment of the culprit lesion. The key secondary clinical endpoints are hazard ratios of the composite of cardiovascular death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization in patients with underlying etiologies at the 12- and 24-month follow-ups. The feasibility of OCT-guided primary PCI for ACS will be assessed by the achievement rates of optimal post-procedural results and safety endpoints. CONCLUSION: The TACTICS registry will provide an overview of the underlying causes of ACS using OCT, and will reveal any difference in clinical outcomes depending on the underlying causes. The registry will also inform on the feasibility of OCT-guided primary PCI for patients with ACS.

A Japanese Dose of Prasugrel versus a Standard Dose of Clopidogrel in Patients with Acute Myocardial Infarction from the K-ACTIVE Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin plus P2Y12 inhibitor is used as a standard therapy for patients with acute myocardial infarction (AMI) treated with drug-eluting stents (DESs). In Japan, clopidogrel was the major P2Y12 inhibitor used for a decade until the new P2Y12 inhibitor, prasugrel, was introduced. Based on clinical studies considering Japanese features, the set dose for prasugrel was reduced to 20 mg as a loading dose (LD) and 3.75 mg as a maintenance dose (MD); these values are 60 and 10 mg, respectively, globally. Despite this dose discrepancy, little real-world clinical data regarding its efficacy and safety exist. METHODS: From the K-ACTIVE registry, based on the DAPT regimen, patients were divided into a prasugrel group and a clopidogrel group. The ischemic event was a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The bleeding event was type 3 or 5 bleeding based on the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: Substantially more patients were prescribed prasugrel (n = 2786) than clopidogrel (n = 890). Clopidogrel tended to be selected over prasugrel in older patients with numerous comorbidities. Before adjustments were made, the cumulative incidence of ischemic events at 1 year was significantly greater in the clopidogrel group than in the prasugrel group (p = 0.007), while the cumulative incidence of bleeding events at 1 year was comparable between the groups (p = 0.131). After adjustments were made for the age, sex, body weight, creatine level, type of AMI, history of MI, approach site, oral anticoagulation therapy, presence of multivessel disease, Killip classification, and presence of intra-aortic balloon pumping, both ischemic and bleeding events became comparable between the groups. CONCLUSION: A Japanese dose of prasugrel was commonly used in AMI patients in the real-world database. Both the prasugrel and clopidogrel groups showed comparable rates of 1 year ischemic and bleeding events.

Impact of atrial fibrillation and the clinical outcomes in patients with acute myocardial infarction from the K-ACTIVE registry.

BACKGROUND: The clinical incidence and impact of atrial fibrillation (AF) in Japanese acute myocardial infarction (AMI) patients is not fully understood. METHODS: To elucidate the clinical incidence and impact of AF on in-hospital mortality in AMI patients, we analyzed a Japanese observational prospective multicenter registry of acute myocardial infarction (K-ACTIVE: Kanagawa ACuTe cardIoVascular rEgistry), which spans 2015 to 2019. A major adverse cardiac event (MACE) was defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. For assessing bleeding events, Bleeding Academic Research Consortium (BARC) type 3 or 5 was used. MACE plus BARC type 3 or 5 bleeding were considered as composite events. The clinical outcomes were followed for 1 year. RESULTS: The total of 5059 patients included 531 patients with AF (10.5%) and 4528 patients with sinus rhythm (SR; 89.5%). AF patients were significantly older and tended to have more comorbidities than SR patients. Oral anticoagulation therapy (OAC) was used in 44% of AF patients while single antiplatelet therapy was selected for 52% of patients with OAC. Crude in-hospital mortality was significantly greater in AF patients than in SR patients (10.4%, 5.0%, respectively, p < 0.01). The multivariate analysis was adjusted for age, sex, diabetes, hypertension, hemodialysis, smoking, previous MI, body mass index, Killip classification, out of hospital cardiac arrest, and OAC. In-hospital mortality was still significantly greater in AF patients than in SR patients in the logistic regression analysis [adjusted odds ratio 2.02 (1.31-3.14)]. AF was an independent risk factor for MACE and composite events in the Cox proportional hazards model [adjusted risk ratio (ARR) 1.91 (1.36-2.69), p < 0.01; ARR 1.72 (1.25-2.36), p < 0.01]. In contrast, AF was not an independent risk factor for bleeding [ARR 1.71 (0.79-3.71), p = 0.18]. CONCLUSION: In Japanese AMI patients, AF was often observed and was associated with worse MACE but not worse bleeding.

The impact of pre-hospital 12-lead electrocardiogram and first contact by cardiologist in patients with ST-elevation myocardial infarction in Kanagawa, Japan.

Background pre-hospital 12-lead electrocardiogram (ECG) by emergency medical service (EMS) personnel at the site of first medical contact (FMC) and the physician of first contact both play important roles in managing patients with ST-elevation myocardial infarction (STEMI). However, in Japan, pre-hospital 12-lead ECG is not routinely performed by EMS personnel at the site of FMC and the physician of first contact is not always a cardiologist. Methods from October 2015 to October 2019, 2035 consecutive STEMI patients transported from the field by ambulance were analyzed from the K-ACTIVE registry. Based on the presence (+) or absence (-) of pre-hospital 12-lead ECG / first contact by cardiologist, patients were divided into 4 groups (+/+, +/-, -/+, -/-). Patient characteristics, FMC to door time, door to device time and in-hospital mortality were compared. Results the numbers of patients in each group were as follows (+/+, n = 987; +/-, n = 211; -/+, n = 610; -/-, n = 227). For patient characteristics, there were significant differences in the prevalence of dyslipidemia and the presence of chest pain. The FMC to door time was similar (median value, +/+, 24 min; +/-, 25 min; -/+, 24 min; -/-, 24 min; p = 0.23). The door to device time was the shortest in the +/+ group (median value, +/+, 65 min; +/-, 80 min; -/+, 69 min; -/-, 88 min; p < 0.0001). Crude in-hospital mortality was the highest in the -/- group (+/+, 3.9%; +/-, 2.4%; -/+, 5.8%; -/-, 11.9%; p < 0.0001). After adjustment for age and sex, the adjusted odds ratios for in-hospital mortality were as follows [odds ratio (with 95% confidence interval) +/+, 0.33 [0.19-0.57]; +/-, 0.19 [0.07-0.52]; -/+, 0.49 [0.29-0.86]; -/-, 1 [reference)]. Conclusion pre-hospital 12-lead ECG and the physician of first contact had a significant impact on the door to device time and in-hospital mortality. Continuous efforts should be made to improve acute management of STEMI.

Clinical significance of prehospital 12-lead electrocardiography in patients with ST-segment elevation myocardial infarction presenting with syncope: from a multicenter observational registry (K-ACTIVE study).

Patients with acute myocardial infarction (AMI) presenting with syncope have poor clinical outcomes partly due to a delay in the diagnosis. Although the impact of prehospital 12-lead electrocardiography (PHECG) on the reduction of first medical contact (FMC)-to-device time and subsequent adverse clinical events in patients with AMI has been demonstrated, the impact of PHECG for the patients presenting with syncope remains to be elucidated. This study aimed to explore the impact of PHECG on 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI) presenting with syncope. From a cohort of multi-center registry [Kanagawa-ACuTe cardIoVascular rEgistry (K-ACTIVE)], a total of 90 consecutive patients with STEMI presenting with syncope were included. The 30-day mortality were compared between patients with PHECG (PHECG group, n = 25) and those without PHECG (non-PHECG group, n = 65). There was no significant difference in the baseline clinical characteristics between the 2 groups. FMC-to-device time was significantly shorter in the PHECG group than in the non-PHECG group (122 [86, 128] vs. 131 [102, 153] min, p = 0.03) due to the shorter door-to-device time. Thirty-day mortality was significantly lower in the PHECG group than in the non-PHECG group (16.0 vs. 44.6%, p = 0.03). In conclusion, PHECG was associated with shorter FMC-to-device time and lower 30-day mortality in patients with STEMI presenting with syncope.

Intravascular Lithotripsy for Vessel Preparation in Severely Calcified Coronary Arteries Prior to Stent Placement　- Primary Outcomes From the Japanese Disrupt CAD IV Study.

BACKGROUND: Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhance vessel compliance and optimize stent deployment. The objective of this study was to assess the safety and effectiveness of IVL treatment of de novo stenoses involving severely calcified coronary vessels in a Japanese population.Methods and Results:Disrupt CAD IV (NCT04151628) was a prospective, multicenter study designed for Japanese regulatory approval of coronary IVL (SWM-1234). The primary safety endpoint was freedom from major adverse cardiac events (MACE) at 30 days. The primary effectiveness endpoint was procedural success (residual stenosis <50% by QCA without in-hospital MACE). Noninferiority analyses for the primary endpoints were performed by comparing the CAD IV cohort with a propensity-matched historical IVL control group. Patients (intent-to-treat, n=64) were enrolled from 8 centers in Japan. Severe calcification by core laboratory assessment was present in all lesions, with a calcified length of 49.8±15.5 mm and a calcium angle of 257.9±78.4° by optical coherence tomography. Primary endpoints were achieved with non-inferiority demonstrated for freedom from 30-day MACE (CAD IV: 93.8% vs. Control: 91.2%, P=0.008), and procedural success (CAD IV: 93.8% vs. Control: 91.6%, P=0.007). No perforations, abrupt closures, or slow/no-reflow events occurred at any time during the procedures. CONCLUSIONS: Coronary IVL demonstrated high procedural success with low MACE rates in severely calcified lesions in a Japanese population.

A novel risk stratification system "Angiographic GRACE Score" for predicting in-hospital mortality of patients with acute myocardial infarction: Data from the K-ACTIVE Registry.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is the most accurate risk assessment system for acute myocardial infarction (AMI), which was proposed in Western countries. However, it is unclear whether GRACE score is applicable to the present Japanese patients with a high prevalence of emergent percutaneous coronary intervention (PCI) and vasospasm. This study aimed to clarify the usefulness of GRACE risk score for risk stratification of Japanese AMI patients treated with early PCI and to evaluate a novel risk stratification system, "angiographic GRACE score," which is the GRACE risk score adjusted by the information of the culprit coronary artery and its flow at pre- and post-PCI, to improve its predicting availability. METHODS: The subjects were 1817 AMI patients who underwent PCI within 24 h of onset between October 2015 and August 2017 and were registered in Kanagawa Acute Cardiovascular (K-ACTIVE) Registry via survey form. The association between the clinical parameters and in-hospital mortality was investigated. RESULTS: A total of 79 (4.3%) in-hospital deaths were identified. The C-statistics for the in-hospital mortality of the GRACE score was 0.86, which was higher than that of the other conventional risk factors, including age (0.65), systolic blood pressure (0.70), heart rate (0.62), Killip classification (0.77), and serum levels of creatinine (0.68) and peak creatine kinase (0.74). The angiographic GRACE score improved the C-statistics from 0.86 of the original GRACE score to 0.89 (p < 0.05). In the setting of the cut-off value at 200, in-hospital mortality in the patients with the angiographic GRACE score <200 was 0.6%, which was relatively lower than those with ≥200, 9.4%. CONCLUSIONS: The GRACE score is a useful predictor of in-hospital mortality among Japanese AMI patients in the PCI era. Moreover, the angiographic GRACE score could improve the predicting availability.

Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years.

OBJECTIVES: The aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging. BACKGROUND: Serial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported. METHODS: In the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT). RESULTS: Luminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference -0.37 mm [95% confidence interval: -0.50 to -0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm2 vs. 7.15 ± 2.16 mm2, mean difference -1.04 mm2 [95% confidence interval: -1.66 to -0.42 mm2]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm2 vs. 1.86 ± 0.64 mm2, mean difference 0.24 mm2 [95% confidence interval: 0.06 to 0.43 mm2]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention. CONCLUSIONS: In this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284).

[A Retrospective Evaluation of the Impact of Multi-disciplinary Approach for Improving the Quality of Anticoagulation Therapy in Ambulatory Patients with Non-valvular Atrial Fibrillation Receiving Warfarin].

While percent time within therapeutic range (%TTR) of international normalized ratio of prothrombin time (PT-INR) represents the quality of anticoagulation therapy with warfarin, it is often maintained less than 50% in patients with non-valvular atrial fibrillation (NVAF). We aimed to study if implementation of a multi-disciplinary ambulatory anticoagulation service (MAAS) may improve %TTR. Collaborating with cardiologists at Kanto Rosai Hospital, we conducted a MAAS for NVAF patients receiving warfarin from April 2013 to December 2015. Patients who agreed to utilize the service in addition to their appointments with cardiologists visited pharmacists to have counseling about diet, concomitant medications, and lifestyle. According to a protocol, pharmacists made dose adjustment proposals to cardiologists, if necessary. Upon approval by cardiologists, dose modifications were made. We retrospectively reviewed medical records of the patients who participated in the MAAS before and during the service. The study protocol was approved by the institutional review board. We identified 78 eligible patients (44 males and 34 females, aged 51 to 91 years). Their median %TTR increased significantly (p<0.05) from 57% during the pre-MAAS period to 77% during the MAAS period. In addition, the median percent time below therapeutic range (%TBTR) decreased significantly (p<0.05) from 35% during the baseline period to 11% during the MAAS period. The present study indicates that MAAS improves the quality of anticoagulation therapy with warfarin in ambulatory patients with NVAF. Further prospective, randomized studies with a greater number of patients are required to confirm the results of the present study.

Sex-Related Differences in In-Hospital Mortality in Japanese ST-Elevation Acute Myocardial Infarction Patients Presenting to Hospital in the 24 Hours After Symptom Onset　- Results From K-ACTIVE.

Background: Despite the drastic advances in clinical care for patients with acute ST-elevation myocardial infarction (STEMI), female STEMI patients have higher in-hospital mortality rates than male patients. This study assessed the influence of sex on in-hospital mortality in STEMI patients in Kanagawa Prefecture, Japan. Methods and Results: From October 2015 to June 2018, 2,491 consecutive STEMI patients (23.9% female) who presented to hospital in the 24 h after symptom onset were analyzed. The female patients were 9 years older and less frequently had diabetes, smoking and prior MI than male patients. Pre-hospital managements, including prehospital 12-lead electrocardiography, and symptom-to-door time were similar between the sexes. A door-to-device time ≤90 min was achieved in 61.3% of female cases and in 65.0% of male cases (P=0.13). Reperfusion therapy was provided to 94.6% of female and 97.6% of male patients (P<0.001). In-hospital mortality rate was not significantly different between female and male patients (6.6% vs. 7.8%, P=0.37). On multivariate logistic regression analysis, female sex itself was not associated with in-hospital mortality (OR, 1.52; 95% CI: 0.67-3.47, P=0.32). Conclusions: There was no sex discrepancy in the in-hospital mortality of STEMI patients in this study. Guideline-based treatment, such as advanced pre-hospital management and a high use of reperfusion therapy might have attenuated the sex-related differences in the in-hospital mortality.

Radial Versus Femoral Approach for Percutaneous Coronary Intervention: MACE Outcomes at Long-Term Follow-up.

OBJECTIVE: To compare the main outcomes of radial versus femoral access at long-term follow-up. BACKGROUND: Little is known about the long-term major cardiovascular events and bleeding complications of patients undergoing percutaneous coronary intervention (PCI) with radial vs femoral approach. METHODS: A total of 1107 patients from the CENTURY II trial were included. To minimize baseline differences between radial and femoral groups, we applied propensity-score matching for this comparison. RESULTS: In this multicenter study, the radial approach was used in 73.4% of patients. After propensity-score matching, baseline and procedural characteristics were comparable between both groups. Procedural success was high and similar in radial and femoral approaches (98.2% vs 97.5%; P=.47) while radial access was associated with a shorter hospital stay (1.69 ± 1.92 days vs 2.08 ± 1.98 days; P<.01). The short-term bleeding and vascular complication rates were significantly lower in the radial group (1.7% vs 6.2% [P<.001 in-hospital] and 2.7% vs 9.6% [P<.001 at 1-month follow-up]). At 3-year follow-up, radial access was associated with lower rates of all-cause mortality (3.9 vs 6.9%; P=.04) and cardiovascular death (2.1 vs 4.9%; P=.02). The composite of all-cause mortality, myocardial infarction, and revascularization showed no differences between groups (18.2 vs 21.1%; P=.29). CONCLUSIONS: Compared to the femoral approach, the radial approach is associated with significantly lower long-term all-cause mortality rate as well as lower in-hospital and short-term bleeding rates. These results suggest additional long-term benefits of radial access for PCI, but should be interpreted within the context of the current study and further verified in future studies.

Multislice computed tomography assessment of everolimus-eluting Absorb bioresorbable scaffolds in comparison with metallic drug-eluting stents from the ABSORB Japan randomised trial.

AIMS: Blooming artefacts limit accurate coronary assessment by multislice computed tomography (MSCT) in metallic stents. We sought to investigate whether bioresorbable vascular scaffolds (BVS) could be better assessed by MSCT. METHODS AND RESULTS: Among 400 patients in the randomised ABSORB Japan trial, a pre-specified MSCT substudy was performed in 98 patients (103 lesions) in the BVS arm and 49 patients (49 lesions) in the cobalt-chromium everolimus-eluting stent (CoCr-EES) arm at 13 months prior to follow-up angiography. The assessability of BVS by MSCT was superior to that of CoCr-EES (94% versus 67%, p<0.001). Blooming artefacts were the main reason CoCr-EES could not be analysed (29%), while marker artefacts precluded analysis in 1.1% of BVS. In the CoCr-EES arm, non-assessable lesions were more prevalent in segments with 2.5 mm stents compared to 3.0 or 3.5 mm stents (75.0% versus 23.5%, p=0.01), while in the BVS arm image quality was good regardless of the diameter. The in-device minimal lumen diameter by MSCT was smaller than that by QCA with a difference of 0.61 mm in the CoCr-EES arm, vs. only 0.026 mm in the BVS arm. CONCLUSIONS: The feasibility of MSCT assessment of BVS-treated lesions was greater than that for lesions with CoCr-EES.