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Background: Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited., Method: We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels., Results: CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period., Conclusions: Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: There is a scarcity of data evaluating the effect of peripheral artery disease (PAD) on long-term mortality after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in patients with severe coronary artery disease in real-world practice., Methods: Among 14,867 consecutive patients who underwent their first coronary revascularization with PCI or isolated CABG between 2011 and 2013 in the CREDO-Kyoto PCI/CABG registry Cohort-3, the current study population consisted of 3380 patients with three-vessel coronary artery disease or left main coronary artery disease. Long-term clinical outcomes were compared between PCI and CABG stratified by the presence or absence of PAD. Median clinical follow-up was 5.9 (IQR: 5.1-6.8) years., Results: There were 461 patients with PAD (PCI: N = 307, CABG: N = 154), and 2919 patients without PAD (PCI: N = 1823, CABG: N = 1096). The cumulative 5-year mortality after coronary revascularization was 31.2 % in patients with PAD and 16.2 % in those without PAD (p < 0.0001). There was a higher risk of PCI relative to CABG for all-cause death in patients with and without PAD (adjusted HR, 1.59; 95%CI, 0.99-2.53; p = 0.054, and HR, 1.25; 95%CI, 1.01-1.56; p = 0.04) without interaction (p interaction p = 0.48); Nevertheless, there was no excess risk of PCI relative to CABG for cardiovascular death regardless of PAD., Conclusions: The long-term mortality after coronary revascularization was significantly higher in severe CAD patients with PAD than those without PAD. There was a higher mortality risk of PCI relative to CABG in patients with and without PAD without interaction, which was mainly driven by excess non-cardiovascular deaths., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A comprehensive cardiac rehabilitation (CR) program is recommended for coronary artery disease (CAD). However, many facilities do not have established programs for dietary guidance and patient education, resulting in an exercise-based CR program and limited efficacy for secondary prevention., Methods and Results: A pilot study will be conducted to develop an online Japanese-style intensive cardiac rehabilitation (J-ICR) program for Japanese patients with CAD and will examine adherence, safety, and efficacy. Twenty-four patients diagnosed with stable CAD will be randomly assigned in a 1 : 1 ratio to either an early or late-phase group. The program will comprise the following four parts: exercise sessions; dietary education centered on "the Japan diet"; mindfulness; and group support, with a frequency of 3 h per session, once a week for 12 weeks (a total of 36 h). The primary endpoint will be program feasibility, determined by examining its adherence. Physical examination and function, stress-coping skills, risk of classic CAD (e.g., lipid profile, glucose tolerance, and blood pressure), and dietary changes will be assessed as secondary endpoints., Conclusions: The online J-ICR program is designed as a comprehensive CR program for Japanese patients with CAD. If this program shows high adherence and an improvement in CAD risk factors, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers., Competing Interests: K.O. is a member of Circulation Reports’ Editorial Team. The authors declare that there are no conflicts of interest. Conflicts of interest were reviewed by the Kyoto University Clinical Research Conflict of Interest Review Committee in accordance with the Kyoto University Conflict of Interest Policy and Kyoto University Conflict of Interest Management Regulations., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Background: Early arrhythmia recurrences commonly occur after atrial fibrillation (AF) ablation because of irritability and inflammation of left atrium. We hypothesized that short-term use of Saireito would be effective in reducing frequent atrial tachyarrhythmias in the early-phase post-ablation., Methods: One hundred patients undergoing catheter ablation for symptomatic AF were randomly assigned to either a 30-day use of Saireito or control group. The primary endpoint was total number of episodes of frequent atrial tachyarrhythmias including definite recurrent AF and frequent premature atrial contractions during the 30-day treatment period post-ablation., Results: Three (6.0%) out of 50 patients treated with Saireito discontinued the drug because of adverse symptoms. The Saireito group was associated with a numerically lower number of episodes of frequent atrial tachyarrhythmias than the control group (3.1 versus 5.2 times, P = 0.17). The mean daily episodes of frequent atrial tachyarrhythmias were significantly fewer in the Saireito group during Day-6 to Day-10 (0.12/day versus 0.27/day, P = 0.03), and during Day-11 to Day-15 (0.08/day versus 0.24/day, P = 0.001). The prevalence of adverse symptoms during the 30-day treatment period was significantly higher in the Saireito group (18.0% versus 2.0%, P = 0.005)., Conclusions: Thirty-day use of Saireito following AF ablation was associated with a tendency toward reduced number of episodes of frequent atrial tachyarrhythmias during the treatment period, with more pronounced effect in the first two weeks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kawaji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (P interaction =0.37)., Conclusions: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Background: Prophylactic embolization of the inferior mesenteric artery (IMA) during endovascular aneurysm repair (EVAR) is recommended to prevent type 2 endoleak (T2EL). However, the impact of patent lumbar arteries (LAs) on T2ELs and aneurysm diameter has not been elucidated., Methods: Fifty-seven consecutive patients who underwent EVAR at our institution between January 2013 and September 2022 and whose IMA had been occluded preoperatively or newly occluded postoperatively were included in the study. Predictive factors for aneurysm sac enlargement, sac shrinkage, and T2EL were investigated., Results: T2ELs occurred in 22.8% of the patients. The 4-year cumulative incidence rates of sac enlargement and shrinkage were 6.7% and 64.6%, respectively. The number of postoperative patent LAs was identified as a risk factor for T2ELs (95% confidence interval [CI]: 1.54-12.7, P = 0.0065). The number of postoperative patent LAs was found to be a significant predictor of sac enlargement (adjusted hazard ratio [AHR] 3.15, 95% CI: 1.43-6.96, P = 0.0045) and shrinkage (AHR 0.63, 95% CI: 0.43-0.91, P = 0.014)., Conclusions: The current study demonstrated that the number of postoperative patent LAs had a significant impact on the development of T2ELs and the change in aneurysm diameter in patients in whom the IMA was occluded after EVAR., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The aim of the current study was to elucidated the reliable atrial fibrillation (AF) drivers identified by CARTOFINDER using OctaRay catheter., Methods and Results: The reliability of focal and rotational activations identified by CARTOFINDER using OctaRay catheter was assessed by the sequential recordings in each site of both atrium before and after pulmonary vein isolation (PVI) in 10 persistent AF patients. The outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI as reliable focal and rotational activations. The study results were compared with those under use of PentaRay catheter (N = 18). Total 68928 points of 360 sites in OctaRay group and 24 177 points of 311 sites in PentaRay were assessed. More focal activation sites were identified in OctaRay group than PentaRay group (7.9% vs. 5.7%, p < .001), although the reproducibility rate and the stability rate were significantly lower in OctaRay group (45.3% vs. 58.9%, p < .001; 11.2% vs. 28.4%, p < .001). Meanwhile, the prevalence of reproducible focal activation sites among overall points was comparable (3.6% vs. 3.3%, p = .08). Regarding rotational activation, more rotational activation sites were identified in OctaRay group (5.1% vs. 0.2%, p < .001), and the reproducibility rate and the stability rate were significantly higher in OctaRay group (45.2% and 12.5% vs. 0.0%, p < .001). Both reliable focal and rotational activation sites were characterized by significantly shorter AF-cycle length (CL) and higher repetition of focal and rotational activations during the recordings compared with the sites of non or unreliable focal and rotational activations., Conclusion: In CARTOFINDER, OctaRay catheter could identify reliable focal activation with high resolution and reliable rotational activation compared with PentaRay catheter. The repetitive focal and rotational activations with short AF-CL could be the potential target during ablation., (© 2023 Wiley Periodicals LLC.)

Objective: The frozen lesion formation created by cryoballoon ablation, especially with non-occluded applications, has not been fully evaluated. This study aimed to validate the lesion size under different cryoballoon ablation settings: application duration, push-up technique, and laminar flow., Methods: The frozen lesion size was evaluated immediately after ending the freezing with three different application durations (120, 150, and 180 seconds) in porcine hearts (N = 24). During the application, the push-up technique was applied at 10, 20, and 30 seconds after starting the freezing with or without laminar flow., Results: The lesion size was significantly correlated with the nadir balloon temperature (P<0.001). The lesion volume became significantly larger after 150 seconds than 120 seconds (1272mm3 versus 1709mm3, P = 0.004), but not after 150 seconds (versus 1876mm3 at 180 seconds, P = 0.29) with a comparable nadir balloon temperature. Furthermore, the lesion volume became significantly larger with the push-up technique with the largest lesion size with a 20-second push-up after the freezing (1193mm3 without the push-up technique versus 1585mm3 with a push-up at 10 seconds versus 1808mm3 with a push-up at 20 seconds versus 1714mm3 with a push-up at 30 seconds, P = 0.04). Further, the absence of laminar flow was not associated with larger lesion size despite a significantly lower nadir balloon temperature., Conclusion: The frozen lesion size created by cryoballoon ablation became larger with longer applications at least 150 seconds and with a push-up technique especially at 20 seconds after the freezing., Competing Interests: The authors declared that no competing interests exist., (Copyright: © 2024 Kawaji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There were no data comparing the in-hospital outcomes after transcatheter aortic valve implantation (TAVI) with those after surgical aortic valve replacement (SAVR) in Japan. Among consecutive patients with severe AS between April 2018 and December 2020 in the CURRENT AS Registry-2, we identified 1714 patients who underwent aortic valve replacement (TAVI group: 1134 patients, and SAVR group: 580 patients). Patients in the TAVI group were much older (84.4 versus 73.6 years, P < 0.001) and more often had comorbidities than those in the SAVR group. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group (0.6% versus 2.2%). After excluding patients with dialysis, in-hospital death rate was very low and comparable in the TAVI and SAVR groups (0.6% versus 0.8%). The rates of major bleeding and new-onset atrial fibrillation during index hospitalization were higher after SAVR than after TAVI (72% versus 20%, and 26% versus 4.6%, respectively), while the rate of pacemaker implantation was higher after TAVI than after SAVR (8.1% versus 2.4%). Regarding the echocardiographic data at discharge, the prevalence of patient-prosthesis mismatch was lower in the TAVI group than in the SAVR group (moderate: 9.0% versus 26%, and severe: 2.6% versus 4.8%). In this real-world data in Japan, TAVI compared with SAVR was chosen in much older patients with more comorbidities with severe AS. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group., (© 2023. The Author(s).)

There is a scarcity of studies evaluating statin discontinuation in patients with coronary artery disease in real-world practice. In 11,144 patients who underwent first coronary revascularization and taking statins in the CREDO-Kyoto Registry Cohort-3, we evaluated the incidence of statin discontinuation, defined as stopping statins for at least 2 months. The reasons for statin discontinuation included nonadherence, side effects, worsening co-morbidities, surgery, prescription error, and direction by physicians for other reasons. During a median 6 years of follow-up, the cumulative incidence of statin discontinuation was 6.1% at 1 year, 12.4% at 3 years, 17.4% at 5 years, and 21.4% at 7 years. The major components of the reasons for statin discontinuation were nonadherence, side effects, and worsening co-morbidities. Compared with patients with statin discontinuation because of other reasons, patients with statin discontinuation because of nonadherence more often had younger age, men, acute coronary syndrome, and current smoking; patients with statin discontinuation because of side effects more often had liver cirrhosis; and patients with statin discontinuation because of worsening co-morbidities more often had advanced age and co-morbidities such as malignancy. Statin discontinuation was strongly associated with subsequent mortality (hazard ratio [HR] 3.54; 95% confidence interval [CI] 3.18 to 3.94, p <0.001), which was consistent, regardless of the reasons, except for the small group of patients with prescription error (nonadherence: HR 2.35, 95% CI 1.69 to 3.27, p <0.001; side effects: HR 2.48, 95% CI 1.84 to 3.34, p <0.001; worsening co-morbidities: HR 22.08, 95% CI 18.55 to 26.29, p <0.001). In conclusion, in real-world practice, approximately 1 in 5 patients discontinued statins after coronary revascularization during a median of 6 years of follow-up. Statin discontinuation was associated with subsequent mortality., Competing Interests: Declaration of Competing Interest Dr. Morimoto reports lecturer's fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis, and Toray and manuscript fees from Bristol-Myers Squibb and Kowa and served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb, and Sanofi. Dr. Shiomi reports personal fees from Abbott Vascular, Boston Scientific, and Daiichi Sankyo. Dr. Ehara reports personal fees from Abbott vascular Japan, Bayer, Boehringer Ingelheim (Bristol), Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifescience, Medtronic, Pfizer (New York, NY, United States), Takeda, and Terumo. Dr. Kimura reports personal fees from Abbott Vascular, Abiomed, Astellas, Astellas Amgen BioPharma, AstraZeneca, Bayer, Boston Scientific, Boehringer Ingelheim-Myers Squibb, Chugai Pharmaceutical, Edwards Lifescience, EISAI, Daiichi Sankyo, Interscience, Japan Society for the Promotion of Science, Kowa, Kowa Pharmaceutical, Lifescience, Medical Review, MSD, MSD Life Science Foundation, Mitsubishi Tanabe Pharma, Novartis Pharma, Ono Pharmaceutical, OrbusNeich, Otsuka Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Philips, Public Health Research Foundation, Sanofi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Terumo, Toray, and Tsumura. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is a paucity of data on the effect of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with standard PCI or coronary artery bypass grafting (CABG) in patients with multivessel disease., Methods and results: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI including the left anterior descending coronary artery using IVUS aiming to meet the prespecified criteria for optimal stent expansion. We conducted propensity score matching analyses between the OPTIVUS group and historical PCI or CABG control groups from the CREDO-Kyoto registry cohort-3 (1,565 and 899 patients) fulfilling the inclusion criteria for this study. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. In the propensity score-matched cohort (OPTIVUS vs. historical PCI control: 926 patients in each group; OPTIVUS vs. historical CABG control: 436 patients in each group), the cumulative 1-year incidence of the primary endpoint was significantly lower in the OPTIVUS group than in the historical PCI control group (10.4% vs. 23.3%; log-rank P<0.001) or the historical CABG control group (11.8% vs. 16.5%; log-rank P=0.02)., Conclusions: IVUS-guided PCI targeting the OPTIVUS criteria combined with contemporary clinical practice was associated with superior clinical outcomes at 1 year compared with not only the historical PCI control, but also the historical CABG control.

Post-contrast acute kidney injury (PC-AKI) is a common complication after percutaneous coronary intervention (PCI). However, it is unclear whether or not the effects of PC-AKI on long-term clinical outcomes were different between emergent and elective procedures. Among patients enrolled in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort 3, we identified 10,822 patients treated using PCI (emergent PCI stratum: n = 5,022 [46%] and elective PCI stratum: n = 5,860 [54%]). PC-AKI was defined as ≥0.3 mg/100 ml absolute or 1.5-fold relative increase of serum creatinine within 72 hours after PCI. The incidence of PC-AKI was significantly higher after emergent PCI than after elective PCI (10.5% vs 3.7%, p <0.001). In the multivariable logistic regression model, emergent PCI was the strongest independent risk factor for PC-AKI in the entire study population. The excess adjusted risk of patients with PC-AKI relative to those without remained significant for all-cause death in both the emergent and elective PCI strata (hazard ratio 1.87, 95% confidence interval 1.59 to 2.21, p <0.001 and hazard ratio 1.31, 95% confidence interval 1.03 to 1.68, p = 0.03, respectively). There was a significant interaction between the PCI setting (emergent and elective) and the effect of PC-AKI on all-cause death, with a greater magnitude of effect in the emergent PCI stratum than in the elective PCI stratum (p for interaction = 0.01). In conclusion, the incidence of PC-AKI was 2.8 times higher after emergent PCI than after elective PCI. The excess mortality risk of PC-AKI relative to no PC-AKI was greater after emergent PCI than after elective PCI., Competing Interests: Declaration of Competing Interest Dr. Shiomi reports modest honoraria from Abbott Vascular and Boston Scientific. Dr. Morimoto reports modest honoraria from Bayer and Kowa and modest expert witness from Boston Scientific and Sanofi. Dr. Furukawa reports modest honoraria from Bayer, Kowa, and Sanofi. Dr. Nakagawa reports modest research grant from Abbott Vascular and Boston Scientific and modest honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr. Kimura reports significant honoraria from Abbott Vascular and modest honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Intracardiac dynamics during atrial fibrillation(AF) complicated by heart failure(HF) are not fully understood. The aim of this study was to evaluate the impact of intracardiac dynamics assessed by echo-vector flow mapping on AF complicated by HF., Methods and Results: We enrolled 76 AF patients receiving sinus restoration therapy and assessed energy loss(EL) by echo-vector flow mapping during both AF rhythm and sinus rhythm. Patients were divided into 2 groups according to serum NT-proBNP level: high NT-proBNP group(≥1800 pg/ml during AF rhythm: N = 19), and low NT-proBNP group(N = 57). Outcome measures were average ELs/stroke volume(SV) in left ventricle(LV) and left atrium(LA). Average EL/SVs during AF rhythm in the LV and LA were significantly larger in the high NT-proBNP group than the low NT-proBNP group(54.2 mE/m·L versus 41.2 mE/m·L, P = 0.02; 3.2 mE/m·L versus 1.9 mE/m·L, P = 0.01). The significantly larger EL/SV in the high NT-proBNP group was recorded for maximum EL/SVs. In patients with high NT-proBNP, large vortex formation with extreme EL was detected in the LV and LA during the diastolic phase. After sinus restoration, the average decrease of EL/SV in the LV and LA was larger in the high NT-proBNP group(-21.4 mE/m·L versus +2.6 mE/m·L, P = 0.04; -1.6 mE/m·L versus -0.3 mE/m·L, P = 0.02). Average EL/SV during sinus rhythm did not significantly differ between the high and low NT-proBNP groups in the LV and LA., Conclusions: High EL during AF rhythm as intracardiac energy inefficiency was associated with high serum NT-proBNP levels and improved after sinus restoration., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD)., Methods and results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002)., Conclusions: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Background: The characteristics of atrial fibrillation (AF) drivers identified by CARTOFINDER have not been thoroughly evaluated. Therefore, the current study was sought to validate the reliability of AF drivers., Methods: The reliability of focal and rotational activation identified by CARTOFINDER during AF was assessed by the sequential recordings in each site before and after pulmonary vein isolation (PVI) in 27 persistent AF patients. The primary outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI., Results: Among 32,135 points in 509 sites, focal activation was identified in 1775 points (5.5%) with a repetition of 11 (6-26) times during the recording. Rotational activation was identified in 132 points (0.4%) with a repetition number of 21 (14-21) times. AF drivers had significantly higher voltage and shorter AF cycle length than non-AF driver sites. The reproducibility rate of focal activation during the sequential recordings was 57.8% and increased with the repetition number. The reproducibility rate of rotational activation was 37.4%. The prevalence and the reproducibility rate of focal activation in post-PVI were significantly lower than pre-PVI (5.3% versus 6.0%, P = 0.02; 53.4% versus 63.6%, P < 0.001). The stability rate of focal activation between pre- and post-PVI was only 28.3% but increased with the repetition number. There was no stable rotational activation between pre- and post-PVI., Conclusions: The reproducibility of AF drivers, especially focal activation, identified by CARTOFINDER is relatively favorable, but the stability between pre- and post-PVI was poor. These results depended on the repetition number during the recording., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era., Methods and results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively., Conclusions: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Aims: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease., Methods and Results: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001)., Conclusions: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD., Competing Interests: The authors have declared that no competing interests exist.

Activated clotting time (ACT) kinetics under uninterrupted oral anticoagulants (OACs) has not been fully evaluated. The present study is sought to validate ACT kinetics including stability under uninterrupted use of OACs during an ablation procedure in daily clinical practice. We prospectively enrolled consecutive 554 patients with atrial fibrillation who underwent catheter ablation procedure under uninterrupted OACs. We evaluated ACT kinetics at an interval of 15 minutes during the procedure and periprocedural complications among 5 OACs (dabigatran [N = 46], rivaroxaban [N = 125], apixaban [N = 129], edoxaban [N = 184], and warfarin [N = 70]). Compared with the dabigatran group, time to achieve target ACT was significantly longer in the rivaroxaban and apixaban groups, but not in the edoxaban and warfarin groups (8.7 vs 11.7 minutes, P < .001; 13.3 minutes, P < .001; 8.8 minutes, P = .64; 10.3 minutes, P = .19, respectively). Heparin dose to achieve target ACT was comparable except for the warfarin group, whereas, compared with the dabigatran group, time in therapeutic range of ACT within the first hour was comparable in the rivaroxaban and apixaban group but significantly lower in the edoxaban and warfarin groups (73.7 % vs 63.0%, P = .06; 67.0 %, P = .16; 59.2 %, P = .001; 58.2%, P = .004, respectively). In multiple regression analysis, low body weight, rivaroxaban, apixaban, and morning session had significant associations with time and heparin dose to achieve target ACT, and there were positive associations of dabigatran and apixaban with time in therapeutic range of ACT within the first hour. The incidence of periprocedural complications did not significantly differ among the 5 groups. Under uninterrupted OAC use in daily clinical practice, dabigatran showed faster achievement of target ACT and higher stability of ACT than other OACs., (© 2021, The American College of Clinical Pharmacology.)

Background: ExTRa Mapping™ has developed to visualize rotational activation as atrial fibrillation (AF) drivers. The current study was sought to evaluate the instability of AF drivers by ExTRa Mapping™., Methods: Variation of nonpassively activated ratio (%NP) among three-time repetitive recordings before and after pulmonary vein isolation (PVI) in left atrium was assessed in 26 persistent AF patients. The recoding time was set at 5 or 8 s for the respective patients. The outcome measures included %NP at each recording, mean value of the three-time recordings, and the instability index, which was defined as maximum difference per mean %NP × 100 (%)., Results: Total 683 sites 2049 recordings were assessed. Mean %NP was 33.3(23.3-42.7)%, and higher in sites with severe (≥50%) and patchy low voltage area than those without, but not in those with severe complex fractionated atrial electrogram area. There was significant correlation between actual and mean %NP (R = 0.86, P < .001), but maximum difference among the repetitive recordings was 16(10-24)%. The instability index of %NP was 55.9(30.9-83.6)%, and significantly lower at the recordings of 8 s compared with 5 s (50.6[28.6-78.4]% vs. 60.4[35.0-90.0]%, P = .004). Furthermore, it was higher at sites with lower reliability of the recordings. After PVI, mean %NP significantly decreased (28.7[18.3-36.7]% vs. 37.7[28.7-45.7]%, P < .001), but the instability index significantly increased compared with those before PVI (60.0[35.0-92.7]% vs. 48.9[29.1-75.0]%, P = .001)., Conclusion: Rotational activation as AF drivers assessed by ExTRa Mapping™ is unstable, and repetitive and longer recording is required for the reliable assessment even after PVI., (© 2022 Wiley Periodicals LLC.)

This paper proposes the use of the standing waves created by the interference between transmitted and reflected acoustic signals to recognize the size and the shape of a target object. This study shows that the profile of the distance spectrum generated by the interference encodes not only the distance to the target, but also the distance to the edges of the target surface. To recognize the extent of the surface, a high-resolution distance spectrum is proposed, and a method to estimate the points on the edges by incorporating observations from multiple measurement is introduced. Numerical simulations validated the approach and showed that the method worked even in the presence of noise. Experimental results are also shown to verify that the method works in a real environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumon, Fukunaga, Manabe and Nakatsuma.)

Recently, one observational study showed that patients with ST-segment elevation myocardial infarction (STEMI) without standard cardiovascular risk factors were associated with increased mortality compared with patients with risk factors. This unexpected result should be evaluated in other populations including those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and chronic coronary syndrome (CCS). Among 30,098 consecutive patients undergoing first coronary revascularization in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort-2 and 3, we compared clinical characteristics and outcomes between patients with and without risk factors stratified by their presentation (STEMI n = 8,312, NSTE-ACS n = 3,386, and CCS n = 18,400). Patients with risk factors were defined as having at least one of the following risk factors: hypertension, dyslipidemia, diabetes, and current smoking. The proportion of patients without risk factors was low (STEMI: 369 patients [4.4%], NSTE-ACS: 110 patients [3.2%], and CCS: 462 patients [2.5%]). Patients without risk factors compared with those with risk factors more often had advanced age, low body weight, and malignancy and less often had history of atherosclerotic disease and prescription of optimal medical therapy. In patients with STEMI, patients without risk factors compared with those with risk factors were more often women and more often had atrial fibrillation, long door-to-balloon time, and severe hemodynamic compromise. During a median of 5.6 years follow-up, patients without risk factors compared with those with risk factors had higher crude incidence of all-cause death. After adjusting confounders, the mortality risk was significant in patients with CCS (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01 to 1.49, p = 0.04) but not in patients with STEMI (HR 1.06, 95% CI 0.89 to 1.27, p = 0.52) and NSTE-ACS (HR 1.07, 95% CI, 0.74 to 1.54, p = 0.73). In conclusion, among patients undergoing coronary revascularization, patients without standard cardiovascular risk factors had higher crude incidence of all-cause death compared with those with at least one risk factor. After adjusting confounders, the mortality risk was significant in patients with CCS but not in patients with STEMI and NSTE-ACS., Competing Interests: Disclosures Dr. Morimoto receives lecturer's fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis, and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; and served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb, and Sanofi. Dr. Shiomi receives personal fees from Abbott Vascular, Boston Scientific, and Daiichi Sankyo. Dr. Kato receives honoraria from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Bristol-Meyers Squibb, Daiichi Sankyo, Merck Sharp & Dohme KK, Ono Pharmaceutical, Pfizer, Takeda, Tanabe-Mitsubishi; and research fund from Abbott Vascular, and Ono Pharmaceutical. Dr. Furukawa receives honoraria from Ono Pharmaceutical, Novartis, Daiichi Sankyo, Bayer, Otsuka Pharmaceutical, Kowa, Takeda, Sumitomo Dainippon Pharma, Pfizer, Bristol-Myers Squibb, and Sanofi. Dr. Nakagawa receives grant from Abbott Vascular and Boston Scientific, and personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, and Daiichi Sankyo. Dr. Kimura receives personal fees from Abbott Vascular, Abiomed, Astellas, Astellas Amgen BioPharma, AstraZeneca, Bayer, Boston Scientific, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Edwards Lifescience, Eisai, Daiichi Sankyo, Interscience, Japan Society for the Promotion of Science, Kowa, Kowa Pharmaceutical, Lifescience, Medical Review, Merck Sharp & Dohme, MSD Life Science Foundation, Mitsubishi Tanabe Pharma, Novartis Pharma, Ono Pharmaceutical, OrbusNeich, Otsuka Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Philips, Public Health Research Foundation, Sanofi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Terumo, Toray, and Tsumura. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The detailed causes of death in non-ST-segment-elevation myocardial infarction (NSTEMI) have not been adequately evaluated compared to those in ST-segment elevation myocardial infarction (STEMI)., Methods: The study population was 6,228 AMI patients who underwent percutaneous coronary intervention (STEMI: 4,625 patients and NSTEMI: 1,603 patients). The primary outcome was all-cause death., Results: Within 6 months after AMI, the adjusted mortality risk was not significantly different between NSTEMI patients and STEMI patients (HR: 0.83, 95%CI: 0.67-1.03, P = 0.09). Regarding the causes of death within 6 months after AMI, mechanical complications more frequently occurred in STEMI patients than in NSTEMI patients, while proportions of post resuscitation status on arrival and heart failure were higher in in NSTEMI patients than in STEMI patients. Beyond 6 months after AMI, the adjusted mortality risk of NSTEMI relative to STEMI was not significantly different. (HR: 1.04, 95%CI: 0.90-1.20, P = 0.59). Regarding causes of death beyond 6 months after AMI, almost half of deaths were cardiovascular causes in both groups, and breakdown of causes of death was similar between NSTEMI and STEMI., Conclusion: The mortality risk within and beyond 6 months after AMI were not significantly different between STEMI patients and NSTEMI patients after adjusting confounders. Deaths due to post resuscitation status and heart failure were more frequent in NSTEMI within 6 months after AMI., Competing Interests: Dr. Shiomi reports modest honoraria from Abbott Vascular, and Boston Scientific. Dr. Morimoto reports modest honoraria from Bayer and Kowa, and modest expert witness from Boston Scientific and Sanofi. Dr. Kato reports modest honoraria from Daiichi-Sankyo, Ono Pharmaceutical, AstraZeneca, Tanabe-Mitsubishi, Bayer, Phizer, Bristol-Meyers Squibb, Boehringer ingelheim, Takeda, MSD KK, Amgen, and research fund from Ono Pharmaceutical and Abbott Japan. Dr. Ehara reports modest honoraria from Abbott Vascular, Bayer, Boston Scientific, Medtronic, and Terumo. Dr. Furukawa reports modest honoraria from Bayer, Kowa, and Sanofi. Dr. Nakagawa reports modest research grant from Abbott Vascular and Boston Scientific, and modest honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr. Kimura reports significant honoraria from Abbott Vascular, and modest honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. None of the article contents have not been published, nor under consideration for publication in any other journal before appearing in PLOS ONE.

Background: The mechanisms leading to atrial fibrosis in patients with atrial fibrillation (AF), especially in relation to inflammation, remain unclear., Methods and Results: Forty biomarkers were measured in peripheral blood samples collected prior to catheter ablation, and the association with left atrial (LVZ) was evaluated in 16 consecutive patients. The median %LVZ was 17%. In Pearson's correlation analysis, interleukin(IL)-17A and interferon(IFN)-γ showed the most significant positive and negative correlations with %LVZ (R = 0.35 and 0.43, P < 0.001). Furthermore, the IL-17A/IFN-γ ratio was significantly associated with %LVZ (R = 0.65, P = 0.007), as was the macrophage inflammatory protein (MIP)-1δ/IFN-γ ratio (R = 0.73, P = 0.001). The area under the receiver operator characteristics curves of the IL-17A/IFN-γ and MIP-1δ/IFN-γ ratios for detecting severe LVZ (%LVZ ≥ 10% as a reference standard) were 0.88 and 0.90, respectively. The IL-17A/IFN-γ ratio was significantly higher in patients with severe LVZ than those without (1.41 versus 0.97, P = 0.01). Furthermore, the sensitivity, specificity, and accuracy for detecting severe LVZ were 60%, 100%, and 75.0%, respectively, at a cut-off value of 1.3., Conclusions: Among inflammatory biomarkers, the serum IL-17A/IFN-γ ratio was associated with severe left atrial LVZ in patients with AF. However, further studies are needed to clarify the role of inflammatory biomarkers in the development and progression of atrial fibrosis in patients with AF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Purpose: We developed the intracardiac echocardiography (ICE) technique to minimize radiation exposure and other recent technology during ablation procedure for atrial fibrillation (AF). The aim of this study was to validate the impact of the current strategy using the recent technology for AF ablation on outcomes after procedure., Methods: We evaluated the safety and efficacy of the current strategy in consecutive set of patients undergoing first-time ablation for AF (N = 233) compared with the conventional strategy in earlier consecutive set of patients (N = 223). The current strategy included the technique of ICE to reduce radiation exposure, Ablation Index ® -guided pulmonary veins isolation, and minimum substrate ablation targeting only for induced AF. Outcome measures were radiation exposure, procedure time, in-hospital adverse outcomes, and event-free survival from tachyarrhythmias., Results: Puncture-to-ablation time was slightly, but significantly increased in the current strategy than in the conventional strategy (48.0 minutes vs 44.7 minutes, P  = .002), although total procedure time was significantly decreased in the current strategy (143.9 minutes vs 156.9 minutes, P  < .001). Likewise, radiation time and absorbed dose were significantly decreased in the current strategy (9.8 minutes vs 38.8 minutes, P  < .001; 102.3 mGy vs 490.5 mGy, P  < .001). The incidence of overall in-hospital adverse outcomes was 3.9% in the current strategy and each complication rate was comparable with the conventional protocol. The event-free survival from recurrent atrial tachyarrhythmias was not significantly different between two groups (72.3% vs 77.1% at 2-year, P  = .32)., Conclusion: The current strategy using the recent technology with ICE, lesion index, and minimum substrate ablation was feasible and reduced total procedure time and radiation exposure. However, the arrhythmia-free survival could not be improved., Competing Interests: Authors declare no conflict of interests for this article., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Objective: To evaluate changes in demographics, clinical practices and long-term clinical outcomes of patients with ST segment-elevation myocardial infarction (STEMI) before and beyond 2010., Design: Multicentre retrospective cohort study., Setting: The Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) AMI Registries Wave-1 (2005-2007, 26 centres) and Wave-2 (2011-2013, 22 centres)., Participants: 9001 patients with STEMI who underwent coronary revascularisation (Wave-1: 4278 patients, Wave-2: 4723 patients)., Primary and Secondary Outcome Measures: The primary outcome was all-cause death at 3 years. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, target vessel revascularisation, ischaemia-driven target vessel revascularisation, any coronary revascularisation and any ischaemia-driven coronary revascularisation., Results: Patients in Wave-2 were older, more often had comorbidities and more often presented with cardiogenic shock than those in Wave-1. Patients in Wave-2 had shorter onset-to-balloon time and door-to-balloon time, were more frequently implanted drug-eluting stents, and received guideline-directed medication than those in Wave-1. The cumulative 3-year incidence of all-cause death was not significantly different between Wave-1 and Wave-2 (15.5% and 15.7%, p=0.77). The adjusted risk of all-cause death in Wave-2 relative to Wave-1 was not significant at 3 years (HR 0.92, 95% CI 0.83 to 1.03, p=0.14), but lower beyond 30 days (HR 0.86, 95% CI 0.75 to 0.98, p=0.03). The adjusted risks of Wave-2 relative to Wave-1 were significantly lower for definite stent thrombosis (HR 0.59, 95% CI 0.43 to 0.81, p=0.001) and for any coronary revascularisation (HR 0.75, 95% CI 0.69 to 0.81, p<0.001), but higher for major bleeding (HR 1.34, 95% CI 1.20 to 1.51, p=0.005)., Conclusions: We could not demonstrate improvement in 3-year mortality risk from Wave-1 to Wave-2, but we found reduction in mortality risk beyond 30 days. We also found risk reduction for definite stent thrombosis and any coronary revascularisation, but an increase in the risk of major bleeding from Wave-1 to Wave-2., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form and declare the following: HSh reports personal fees from Abbott Vascular, Boston Scientific and Daiichi Sankyo. TM reports lecturer's fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; serving on advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb and Sanofi. ETK reports grant from Ono Pharmaceutical and reports personal fees from Daiichi Sankyo, AstraZeneca, Bristol-Myers Squibb, Tanabe-Mitsubishi Pharma, Ono Pharmaceutical, MSD KK and Pfizer. NE reports personal fees from Abbott Vascular, Medtronic, Terumo, Bayer, Boston Scientific, Daiichi-Sankyo, Edwards Lifescience, Pfizer, Bristol Myers Squibb, Takeda and Boehringer Ingelheim. YF reports personal fees from Daiichi Sankyo, Bayer, Sanofi, Kowa, Pfizer, Bristol-Myers Squibb, Otsuka Parmaceutical, Sumitomo Dainippon Pharma, Takeda and Ono Pharmaceutical. YN reports grant from Abbott Vascular and Boston Scientific, and reports personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo. TKi reports personal fees from Abbott Vascular, MSD, Eisai, Edwards Lifescience, Ono Pharmaceutical, Tsumura, Medical Review, Kowa, Sanofi, Daiichi Sankyo, Takeda Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Abiomed, Bayer, Bristol-Myers Squibb, Boston Scientific, Lifescience, Toray, Astellas Amgen Biopharma, Astellas, AstraZeneca, Otsuka Parmaceutical, OrbusNeich, MSD Life Science Foundation, Public Health Research Foundation, Chugai Pharmaceutical, Boehringer Ingelheim, Japan Society for the Promotion of Science, Interscience, Philips, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Terumo, Novartis Pharma and Sumitomo Dainippon Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is a scarcity of data on incidence, risk factors, especially clinical severity, and long-term prognostic impact of periprocedural stroke after coronary revascularization in contemporary real-world practice. Among 14,867 consecutive patients undergoing first coronary revascularization between January 2011 and December 2013 (percutaneous coronary intervention [PCI]: N = 13258, and coronary artery bypass grafting [CABG]: N = 1609) in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG registry Cohort-3, we evaluated the details on periprocedural stroke. Periprocedural stroke was defined as stroke within 30 days after the index procedure. Incidence of periprocedural stroke was 0.96% after PCI and 2.13% after CABG (log-rank p <0.001). Proportions of major stroke defined by modified Rankin Scale ≥2 at hospital discharge were 68% after PCI, and 77% after CABG. Independent risk factors of periprocedural stroke were acute coronary syndrome (ACS), carotid artery disease, advanced age, heart failure, and end-stage renal disease after PCI, whereas they were ACS, carotid artery disease, atrial fibrillation, chronic obstructive pulmonary disease, malignancy, and frailty after CABG. There was excess long-term mortality risk of patients with periprocedural stroke relative to those without after both PCI and CABG (hazard ratio 1.71 [1.25 to 2.33], and hazard ratio 4.55 [2.79 to 7.43]). In conclusion, incidence of periprocedural stroke was not negligible not only after CABG, but also after PCI in contemporary real-world practice. Majority of patients with periprocedural stroke had at least mild disability at hospital discharge. ACS and carotid artery disease were independent strong risk factors of periprocedural stroke after both PCI and CABG. Periprocedural stroke was associated with significant long-term mortality risk after both PCI and CABG., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate patient characteristics and long-term outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) in the past two decades., Design: Multicenter retrospective study., Setting: The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) Registry Cohort-2 (2005-2007) and Cohort-3 (2011-2013)., Participants: 3254 patients with NSTEACS who underwent first coronary revascularisation., Primary and Secondary Outcome Measures: The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, any coronary revascularisation and target vessel revascularisation., Results: Patients in Cohort-3 were older and more often had heart failure at admission than those in Cohort-2. The prevalence of PCI, emergency procedure and guideline-directed medical therapy was higher in Cohort-3 than in Cohort-2. In patients who received PCI, the prevalence of transradial approach, drug-eluting stent use and intravascular ultrasound use was higher in Cohort-3 than in Cohort-2. There was no change in 3-year adjusted mortality risk from Cohort-2 to Cohort-3 (HR 1.00, 95% CI 0.83 to 1.22, p=0.97). Patients in Cohort-3 compared with those in Cohort-2 were associated with lower adjusted risks for stroke (HR 0.65, 95% CI 0.46 to 0.92, p=0.02) and any coronary revascularisation (HR 0.76, 95%CI 0.66 to 0.87, p<0.001), but with higher risk for major bleeding (HR 1.25, 95% CI 1.06 to 1.47, p=0.008). The unadjusted risk for definite stent thrombosis was lower in Cohort-3 than in Cohort 2 (HR 0.29, 95% CI 0.11 to 0.67, p=0.003)., Conclusions: In the past two decades, we did not find improvement for mortality in patients with NSTEACS. We observed a reduction in the risks for definite stent thrombosis, stroke and any coronary revascularisation, but an increase in the risk for major bleeding., Competing Interests: Competing interests: HS reports personal fees from Abbott Vascular, Boston Scientific and Daiichi Sankyo. TM reports lecturer’s fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb and Sanofi. NE reports personal fees from Abbott Vascular, Medtronic, Terumo, Bayer, Boston Scientific, Daiichi-Sankyo, Edwards Lifescience, Pfizer, Bristol Myers Squibb, Takeda and Boehringer Ingelheim. YF reports personal fees from Daiichi Sankyo, Bayer, Sanofi, Kowa, Pfizer, Bristol-Myers Squibb, Otsuka Parmaceutical, Sumitomo Dainippon Pharma, Takeda and Ono Pharmaceutical. YN reports grant from Abbott Vascular and Boston Scientific, and reports personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo. TK reports personal fees from Abbott Vascular, MSD, Eisai, Edwards Lifescience, Ono Pharmaceutical, Tsumura, Medical Review, Kowa, Sanofi, Daiichi Sankyo, Takeda Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Abiomed, Bayer, Bristol-Myers Squibb, Boston Scientific, Lifescience, Toray, Astellas Amgen Biopharma, Astellas, AstraZeneca, Otsuka Parmaceutical, OrbusNeich, MSD Life Science Foundation, Public Health Research Foundation, Chugai Pharmaceutical, Boehringer Ingelheim, Japan Society for the Promotion of Science, Interscience, Philips, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Terumo, Novartis Pharma and Sumitomo Dainippon Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE)., Materials and Methods: The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (>60 kg)., Results: Patients with lower body weight were older (70.8 versus 60.9 years, P < 0.001), and more often women (75% versus 38%, P < 0.001), and more often had active cancer (27% versus 19%, P < 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P < 0.001, and 35.8% versus 19.8%, P < 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P < 0.001, respectively)., Conclusions: In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively., Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS., Methods: Among 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure., Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77)., Conclusions: Patients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Electroanatomic voltage mapping (EAVM) of the left atrium (LA) with multielectrodes is usually acquired during sinus rhythm (SR), and the feasibility of EAVM during atrial fibrillation (AF) rhythm is unclear., Methods: We performed EAVM of LA during both SR and AF rhythm in 44 patients undergoing catheter ablation for AF and validated the optimal cutoff value of low-voltage area (LVA) during AF rhythm for detecting LVA defined as bipolar voltages ≤0.5 mV during SR., Results: In each session, mean 829 and 552 points were acquired by multielectrodes during SR and AF rhythm, respectively. Mean proportion of LVA was 4.9% among LA surface area of 276.2 cm 2 . Differences of LVA proportions between SR and AF rhythm were 5.8% (P < 0.001), 4.2% (P < 0.001), 2.7% (P < 0.001), 1.2% (P = 0.01), and -0.5% (P = 0.17) at the cutoff value of 0.4, 0.35, 0.3, 0.25, and 0.2 mV during AF rhythm, respectively. There was a good correlation between LVA proportions during SR and AF rhythm with cutoff value of 0.2 mV (R = 0.88, P < 0.001) and 37 patients (84.1%) had the discrepancy of LVA proportions within 3%. Furthermore, there was no significant difference between LVA proportions at each segment of LA. The discrepancy was relatively large in patients with large LA dimension and LVA during SR., Conclusion: EAVM during AF rhythm was feasible and the optimal cutoff value of LVA was 0.2 mV for detecting LVA ≤ 0.5 mV during SR. However, the evidence is restricted to patients with relatively small LVA., (© 2019 Wiley Periodicals, Inc.)

Limitations of the Ablation Index Background: Ablation index (AI) is a novel marker of lesion quality from radiofrequency (RF) catheter ablation. However, AI reliability has not been fully validated by experimental data. The aim of the present study is to validate AI reliability for estimating lesion size using different settings for RF parameters: contact angle, power delivery, and contact force (CF)., Methods and Results: We evaluated the lesion size in porcine hearts (N = 108) after RF application at three different contact angles to the myocardium: perpendicular (90°), oblique (45°), and parallel (0°). At each angle, RF power at 25, 30, and 35 W was applied at target CF values of 5, 15, and 30 g as measured by the CF sensor to reach target AIs of 300, 400, 500, and 600. AI value was significantly correlated with lesion depth, width, and volume (R = 0.84, 0.82, and 0.87, respectively, all P < 0.001). Lesion depth decreased with smaller contact angles (45° and 0°). Furthermore, high-power RF energy (35 W) resulted in a significantly smaller lesion volume compared with standard-power energy (30 W). There were no significant differences in lesion size among CF settings., Conclusions: AI was strongly correlated with lesion depth, width, and volume, but only within a small range of contact angles and RF power delivery settings., (© 2019 Wiley Periodicals, Inc.)

Objectives: We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR)., Methods: We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50)., Results: The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year., Conclusions: Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy., Trail Registration Number: UMIN000012140., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We developed a novel guidewire-integrated filter device with a handy-folding system (IFD: Inoue filter device). In vitro and in vivo studies were conducted to evaluate the feasibilityof the IFD., Background: Although distal atheromatous and thrombotic embolizations remain unresolved critical issues during catheter interventions, distal protection devices are infrequently used partly because of reduced lower maneuverability., Methods: In the in vitro experiment, we created an experimental circulation model composed of silicone latex tubes, a reservoir, and a roller pump. After the filter device was deployed in the tube, polystyrene fluorescent microspheres were injected and the capture rate was calculated. Ten trials were performed using the IFD and Spider FX. In the in vivo study, five independent operators deployed, and they retrieved the IFD in swine common iliac and internal carotid arteries. The procedural success rate as well as the delivery and retrieval time was evaluated., Results: In the in vitro study, the mean capture rate was 94% and 35% in the IFD and Spider groups, respectively. In the in vivo study, all procedures were successful, with no complications. The mean delivery time was 281 ± 87 s and 194 ± 67 s and the mean retrieval time was 24 ± 9 and 13 ±1 s in the left internal carotid and the left common iliac arteries, respectively., Conclusion: Although further studies and improvements are required, the study results indicate that the IFD is feasible., (© 2017 Wiley Periodicals, Inc.)

Aim: To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy., Methods and Results: Using data of 3815 patients with severe AS in a retrospective multicentre registry [CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry], we compared 3-year clinical outcomes among three groups based on malignancy status: with malignancy currently under treatment including best supportive care (malignancy group), with a history of malignancy without any current treatment (past history group), or without history of malignancy (no malignancy group). Patients in the malignancy group (n = 124) were more often men and had higher prevalence of low body mass index, recurrence of malignancy, anaemia, and asymptomatic status, despite comparable surgical risks and echocardiographic parameters. The malignancy group or the past history group (n = 389) had significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52) than that of the no malignancy group (n = 3302). The excess risk for aortic valve-related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48-1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the malignancy group, the treatment strategy (surgery: n = 16, conservative management: n = 108) was determined based on the clinical status of AS or life expectancy., Conclusions: Malignancy had marked effect on all-cause death and malignancy-related death in patients with severe AS. History of malignancy also had a smaller but significant effect on mortality.

Aims: To evaluate the influence of a history of cancer on clinical outcomes in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI)., Methods and Results: In the Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/coronary artery bypass grafting (CABG) Registry Cohort-2, there were 12 180 CAD patients who received PCI with stents. There were 1109 patients with a history of cancer (cancer group) and 11 071 patients without cancer (non-cancer group). The cumulative 5-year incidences of cardiac death and heart failure (HF) hospitalization were significantly higher in the cancer group than in the non-cancer group (12.4% vs. 7.5%, P < 0.001 and 12.1% vs. 7.6%, P < 0.001, respectively). Even after adjusting for confounders, the excess risk of the cancer group relative to non-cancer group for cardiac death and HF hospitalization remained significant [hazard ratio (HR) 1.27, 95% confidence interval (95% CI) 1.05-1.53; P = 0.02, and HR 1.39, 95% CI 1.13-1.68; P = 0.002, respectively]. Also, the cancer group had a trend toward higher adjusted risk for definite or probable stent thrombosis as compared with the non-cancer group (HR 1.49, 95% CI 0.99-2.16; P = 0.055). The cancer group had significantly higher adjusted risk for all-cause death, non-cardiac death, major bleeding, and non-CABG surgery than the non-cancer group, while the risks for myocardial infarction and stroke were neutral between the two groups., Conclusion: Patients with a history of cancer at the time of PCI had increased risk for cardiac events such as cardiac death and HF hospitalization as well as non-cardiac events such as non-cardiac death, major bleeding, and non-CABG surgery.

Background: The main drawback of current available drug coated balloons (DCB) is that a certain percentage of the coated drug is lost in the bloodstream during its delivery to the target lesion. We integrated the nanoparticle-mediated drug delivery technology and polydimethylsiloxane (PDMS) as a new excipient to facilitate an efficient drug delivery and uptake by endothelial cells. The present study aimed to evaluate the efficacy of the new DCB., Method and Results: The novel DCB were coated with 5.6mg of paclitaxel-incorporated nanoparticles using PDMS. The efficacy of the new DCB was examined in rabbit iliac stent model (n=12) and in the swine in-stent restenosis model (n=8) by quantitative coronary angiography (QCA) and optical coherence tomography (OCT). At 28days follow-up in the swine in-stent restenosis model, the area stenosis was significantly lower in DCB group as compared with that of the control group in OCT analysis (0.31±0.05 vs 0.49±0.06, p=0.04) though there was no significant differences observed in the rabbit iliac stent model in QCA and OCT analysis., Conclusion: The study results indicated that the paclitaxel-incorporated nanoparticle-coated balloon using PDMS has an inhibitory effect for the proliferation of smooth muscle cell in a swine coronary in-stent restenosis model., (Copyright © 2017 Elsevier Inc. All rights reserved.)