Improved Glycemic Control through Robot-Assisted Remote Interview for Outpatients with Type 2 Diabetes: A Pilot Study.

Background and Objectives: Our research group developed a robot-assisted diabetes self-management monitoring system to support Certified Diabetes Care and Education Specialists (CDCESs) in tracking the health status of patients with type 2 diabetes (T2D). This study aimed to evaluate the impact of this system on glycemic control and to identify suitable candidates for its use. Materials and Methods: After obtaining written informed consent from all participants with T2D, the CDCESs conducted remote interviews with the patients using RoBoHoN. All participants completed a questionnaire immediately after the experiment. HbA1c was assessed at the time of the interview and two months later, and glycemic control status was categorized as either "Adequate" or "Inadequate" based on the target HbA1c levels outlined in the guidelines for adult and elderly patients with type 2 diabetes by the Japan Diabetes Society. Patients who changed their medication regimens within the two months following the interview were excluded from the study. Results: The clinical characteristics of the 28 eligible patients were as follows: 67.9 ± 14.8 years old, 23 men (69%), body mass index (24.7 ± 4.9 kg/m2), and HbA1c levels 7.16 ± 1.11% at interview and two months later. Glycemic control status (GCS) was Adequate (A) to Inadequate (I): 1 case; I to A: 7 cases; A to A good: 14 cases; I to I: 6 cases (p-value = 0.02862 by Chi-square test). Multiple regression analyses showed that Q1 (Did RoBoHoN speak clearly?) and Q7 (Was RoBoHoN's response natural?) significantly contributed to GCS, indicating that the naturalness of the responses did not impair the robot-assisted interviews. The results suggest that to improve the system in the future, it is more beneficial to focus on the content of the conversation rather than pursuing superficial naturalness in the responses. Conclusions: This study demonstrated the efficacy of a robot-assisted diabetes management system that can contribute to improved glycemic control.

Characteristics and outcomes in elderly patients with non-valvular atrial fibrillation and high bleeding risk: subanalysis of the J-RHYTHM Registry.

Recently, a once-daily dose of edoxaban (15-mg) has been approved for stroke prevention in non-valvular atrial fibrillation (NVAF) patients aged ≥ 80 years, in whom standard oral anticoagulants are not recommended because of high bleeding risk (HBR), based on the ELDERCARE-AF trial. However, information regarding the characteristics and clinical outcomes among such patients is limited. Thus, this study aimed to clarify the characteristics and event rates in elderly patients with NVAF and HBR defined by the ELDERCARE-AF criteria. Of the 7406 NVAF outpatients included in the J-RHYTHM Registry, 60 patients with creatinine clearance (CrCl) < 15 mL/min were excluded. The remaining 7346 patients (age, 69.7 ± 9.9 years; men, 70.9%; warfarin use, 78.7%) were divided into three groups: Group 1, aged < 80 years (n = 6165); Group 2, aged ≥ 80 years without HBR (n = 584); and Group 3, aged ≥ 80 years with HBR (at least one of the followings; CrCl, 15-30 mL/min, history of bleeding, body weight ≤ 45 kg, and antiplatelet use) (n = 597, eligible for 15-mg edoxaban). Patients in Group 3 had a higher prevalence of comorbidities, and therefore, both higher thromboembolic and bleeding risk scores than in the other groups. During the 2-year follow-up period, the incidence rates (per 100 person-years) of thromboembolism in Groups 1, 2, and 3 were 0.7, 1.5, and 2.1 (P < 0.001), major hemorrhage, 0.8, 1.2, and 2.0 (P < 0.001), and all-cause death, 0.8, 2.6, and 4.6 (P < 0.001), respectively. Adjusted hazard ratios of Group 3 were 1.64 (95% confidence interval 0.89-3.04, P = 0.116) for thromboembolism, 1.53 (0.85-2.72, P = 0.154) for major hemorrhage, and 1.84 (1.19-2.85, P = 0.006) for all-cause death compared with Group 1. The NVAF Patients aged ≥ 80 years with HBR defined by the ELDERCARE-AF criteria were certainly at a higher adverse event risk, especially for all-cause death. Clinical trial registration: The J-RHYTHM Registry is registered in the University Hospital Medicine Information Network (UMIN) Clinical Trials Registry (unique identifier: UMIN000001569) http://www.umin.ac.jp/ctr/ .

Negative correlation between organ heteroplasmy, particularly hepatic heteroplasmy, and age at death revealed by post-mortem studies of m.3243A > G cases.

Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.3243A > G organ heteroplasmy and clinical phenotypes, including the age at death, we combined genetic and pathological examinations from seven unreported and 36 literature cases of autopsied subjects. Clinical characteristics of subjects were as follows: male, 13; female, 28; unknown, 2; the age at death, 36.9 ± 20.2 [4-82] years; BMI, 16.0 ± 2.9 [13.0-22.3]; diabetes, N = 21 (49%), diabetes onset age 38.6 ± 14.2 years; deafness, N = 27 (63%); stroke-like episodes (StLEp), N = 25 (58%); congestive heart failure (CHF), N = 15 (35%); CHF onset age, 51.3 ± 14.5 years. Causes of death (N = 32) were as follows: cardiac, N = 13 (41%); infection, N = 8 (25%); StLEp, N = 4 (13%); gastrointestinal, N = 4 (13%); renal, N = 2 (6%); hepatic, N = 1 (2%). High and low heteroplasmies were confirmed in non-regenerative and regenerative organs, respectively. Heteroplasmy of the liver, spleen, leukocytes, and kidney for all subjects was significantly associated with the age at death. Furthermore, the age at death was related to juvenile-onset (any m.3243A > G-related symptoms appeared before 20) and stroke-like episodes. Multiple linear regression analysis with the age at death as an objective variable showed the significant contribution of liver heteroplasty and juvenile-onset to the age at death. m.3243A > G organ heteroplasmy levels, particularly hepatic heteroplasmy, are significantly associated with the age at death in deceased cases.

Effectiveness and safety of reduced-dose rivaroxaban for elderly patients with non-valvular atrial fibrillation: A subanalysis of the EXPAND study.

BACKGROUND: Establishing the appropriate rivaroxaban dose in older patients with non-valvular atrial fibrillation (NVAF) is important because of the high risk of adverse events. In this EXPAND study subanalysis, we examined the safety and efficacy of standard-dose (15 mg/day) and non-recommended reduced-dose (10 mg/day) rivaroxaban in patients aged ≥65 years with NVAF and preserved renal function. METHODS: The entire analysis population (ALL cohort [n = 3982]; ≥65 years) was divided into early elderly (ELD) (65-74 years [n = 1444]) and late ELD (≥75 years [n = 2386]) sub-cohorts. Each sub-cohort was divided into reduced-dose and standard-dose groups. Kaplan-Meier survival curves with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were used to assess efficacy (thromboembolic events) and safety (hemorrhagic events) outcomes. RESULTS: The aHR for major bleeding did not differ between the dosages in any of the cohorts (aHRs: 0.86-0.93). There were no significant differences in the occurrence of stroke + systemic embolism (SE) or stroke + SE + myocardial infarction (MI) + cardiovascular (CV) death among the cohorts. The aHR for MI/unstable angina + interventional/CV surgery + CV death was higher with 10-mg/day rivaroxaban than 15-mg/day rivaroxaban in the ALL cohort (aHR: 1.56 [95% CI 1.02-2.37], p = 0.039) and the late ELD sub-cohort (aHR: 1.86 [95% CI 1.01-3.42], p = 0.045). CONCLUSIONS: Reduced-dose rivaroxaban may increase the risk of coronary artery events. The use of rivaroxaban 15 mg/day in patients with NVAF aged ≥75 years with preserved renal function was supported.

Causes of death in Japanese people with type 2 diabetes and factors associated with all-cause mortality from a large registry in Japan: the Japan Diabetes Complication and its prevention prospective (JDCP) study-9.

Aims: We aimed to estimate the causes of death and their incidence rates and risk factors for all-cause mortality in Japanese people with type 2 diabetes using baseline data from the Japan Diabetes Complication and its Prevention (JDCP) prospective study. Methods: We analyzed a multicenter prospective cohort of 5944 Japanese people with diabetes aged 40-74 years. Causes of death were categorized as cardiac or cerebrovascular disease, malignancy, infectious disease, accident or suicide, sudden death of unknown cause, and other unknown causes. The Cox proportional hazards model was used to estimate the hazard ratio of all-cause mortality risk factors. Results: The mean age was 61.4 years, and 39.9% of the population was female. Overall, the mortality ratio per 100,000 person-years (95% confidence interval [CI]) was 515.3 (95% CI 445.1-596.9). Malignancies are the most common cause of death among people with type 2 diabetes, accounting for 46.9% of all deaths, followed by cardiac and cerebrovascular diseases at 11.7% and infectious diseases at 3.9%. Higher mortality risk was significantly associated with older age, lower body-mass index, alcohol intake, history of hypertension, and acute myocardial infarction (AMI). Conclusions: The frequency of causes of death in people with type 2 diabetes identified in this study was similar to that from a recent survey on causes of death conducted by the Japan Diabetes Society. A lower body-mass index, alcohol intake, history of hypertension, and AMI were found to be associated with an increased total risk of type 2 diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00628-y.

A Cross-Sectional Study Based on Forty Systematic Reviews of Foods with Function Claims (FFC) in Japan: Quality Assessment Using AMSTAR 2.

BACKGROUND: The Foods with Function Claims (FFC) was introduced in Japan in April 2015 to make more products available that are labeled with health functions. The products' functionality of function claims must be explained by scientific evidence presented in systematic reviews (SRs), but the quality of recent SRs is unclear. This study assessed the quality of SRs in the FFC registered on the Consumer Affairs Agency (CAA) website in Japan. METHODS: We searched the database from 1 April to 31 October 2022. Confidence in the methodological quality of each SR was evaluated by the AMSTAR 2 checklist. RESULTS: Forty SRs were randomly extracted on the basis of the eligibility criteria and recruitment procedures. Overall confidence was rated as "high" (N = 0, 0%), "moderate" (N = 0, 0%), "low" (N = 2, 5%), or "critically low" (N = 38, 95%). The mean AMSTAR 2 score was 51.1% (SD 12.1%; range 19-73%). Among the 40 SRs, the number of critical domain deficiencies was 4 in 7.5% of SRs, 3 in 52.5% of SRs, 2 in 35% of SRs, and 1 in 5% of SRs. Registering the review's protocol and comprehensive search strategies were particularly common deficiencies. Additionally, the risk of bias (RoB) was insufficiently considered. CONCLUSION: Overall, the methodological quality of the SRs based on the FFC, introduced eight years earlier, was very poor. This was especially true in the interpretation and discussion of critical domains, which had many deficiencies in terms of protocol registration, a comprehensive literature search strategy, and accounting for the RoB.

Acute and mid-term outcomes of ablation for atrial fibrillation with VISITAG SURPOINT: the Japan MIYABI registry.

AIMS: The effectiveness of pulmonary vein isolation (PVI) guided by VISITAG SURPOINT (VS) has been demonstrated in Western populations. However, data for Asian populations are limited. VS settings may differ for Asians, given their smaller body size. This study aimed to describe outcomes of radiofrequency atrial fibrillation (AF) ablation guided by VS in a large Asian population. METHODS AND RESULTS: The prospective, observational, multicentre MIYABI registry collected real-world data from patients undergoing VS-guided AF ablation using ThermoCool SmartTouch and ThermoCool SmartTouch SF catheters from 50 Japanese centres. All patients had paroxysmal AF or persistent AF for <6 months. Primary adverse events (PAEs) were evaluated for safety. The primary efficacy endpoint was the proportion of patients with PVI at the end of the procedure. Mid-term effectiveness (up to 12 months) was evaluated by freedom from documented atrial arrhythmias. Of the 1011 patients enrolled, 1002 completed AF ablation. The mean number of VS values per procedure was 428.8 on the anterior wall and 400.4 on the posterior wall. Nine patients (0.9%) experienced PAEs. Upon procedure completion, 99.7% of patients had PVI. Twelve-month freedom from atrial arrhythmia recurrence was 88.5%; 5.7% of patients were re-ablated. At repeat ablation, 54% of RSPV, 73% of RIPV, 70% of LSPV, and 86% of LIPV evaluated remained durably isolated. CONCLUSION: Despite lower anterior wall VS values compared with the CLOSE protocol (≥550), the present study demonstrated comparable efficacy outcomes, indicating that a VS of ≥550 for the anterior wall may not be necessary for Asian patients.

Predictive ability of visit-to-visit blood pressure indices for adverse events in patients with non-valvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry.

Background: We previously reported that standard deviation (SD) of systolic blood pressure (SBP), an index of BP variability, and SBP-time in target range (TTR), an index of BP consistency, were significantly associated with adverse events in patients with non-valvular atrial fibrillation (NVAF). Thus, this study aimed to compare predictive ability for adverse events among visit-to-visit BP variability/consistency indices using data from the J-RHYTHM Registry. Methods: Of 7406 outpatients with NVAF, 7226 (age, 69.7 ± 9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6 ± 5.0 times) during the 2-year follow-up period or until occurrence of an event, were included. As BP consistency for target SBP between 110 and 130 mmHg, SBP-TTR by the Rosendaal method and SBP-frequency in range (FIR) were calculated. Predictive ability was expressed by the area under receiver-operating-characteristic curve (AUC). AUCs of SBP-TTR and SBP-FIR for adverse events were compared with those of SBP-SD by the DeLong's test. Results: SBP-SD, SBP-TTR, and SBP-FIR were 11.0 ± 4.2 mmHg, 49.5 ± 28.3%, and 52.3 ± 23.0%, respectively. AUCs of these indices for thromboembolism, major hemorrhage, and all-cause death were 0.62, 0.64, and 0.63 for SBP-SD; 0.56, 0.55, and 0.56 for SBP-TTR; and 0.55, 0.56, and 0.58 for SBP-FIR; respectively. AUCs of SBP-SD were significantly larger than those of SBP-TTR for major hemorrhage (P = 0.010) and all-cause death (P = 0.014), and SBP-FIR for major hemorrhage (P = 0.016). Conclusion: Among visit-to-visit BP variability/consistency indices, predictive ability of SBP-SD for major hemorrhage and all-cause death was superior to that of SBP-TTR and SBP-FIR in patients with NVAF.

Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

Sex Difference in the Impact of Dual Antiplatelet Therapy using Cilostazol for Secondary Stroke Prevention: A Sub-Analysis of CSPS.com.

AIM: Although some sex differences in stroke have been reported, differences in the effects of antiplatelet therapy for secondary stroke prevention have not been clarified. METHODS: In the Cilostazol Stroke Prevention Study combination trial, patients with high-risk, non-cardioembolic ischemic stroke between 8 and 180 days after onset treated with aspirin or clopidogrel alone were recruited and randomly assigned to receive either monotherapy or dual antiplatelet therapy (DAPT) using cilostazol and followed up for 0.5-3.5 years. The primary efficacy outcome was recurrence of ischemic stroke. The safety outcome was severe or life-threatening hemorrhage. Outcomes were analyzed by sex. RESULTS: A total of 1,320 male patients and 558 female patients were included. The male patients had more risk factors than the female patients. In male patients, the primary endpoint occurred at a rate of 2.0 per 100 patient-years in the DAPT group and 5.1 per 100 patient-years in the monotherapy group (hazard ratio (HR), 0.40; 95% confidence interval (CI), 0.23-0.68). In male patients, DAPT prolonged the time to recurrent stroke by 4.02-fold (95% CI, 1.63-9.96) compared with monotherapy. In female patients, the average annual event rates were 2.7 per 100 patient-years in the DAPT group and 3.3 per 100 patient-years in the monotherapy group (HR, 0.82; 95% CI, 0.37-1.84). Safety outcomes did not differ significantly in both male and female patients. CONCLUSIONS: Long-term DAPT using cilostazol reduced the recurrence of ischemic stroke and prolonged the recurrence-free time in male patients, but not in female patients.

Treatment patterns and satisfaction in patients with type 2 diabetes newly initiating oral monotherapy with antidiabetic drugs in Japan: results from the prospective Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND).

INTRODUCTION: To present longitudinal data from the Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND) in Japan. RESEARCH DESIGN AND METHODS: In this multicenter, prospective, observational cohort study, patients with type 2 diabetes mellitus (T2DM) newly initiated on monotherapy were followed up for 2 years. Primary outcomes included changes in treatment pattern over time, target hemoglobin A1c (HbA1c) attainment and treatment satisfaction per Oral Hypoglycaemic Agent Questionnaire (OHA-Q). RESULTS: Among 1474 enrolled patients (male, 62.1%; mean age, 59.7 years; HbA1c, 8.08%), the oral antidiabetic drug (OAD) monotherapy prescription rate decreased to 47.2% and that of 2 and ≥3 OADs increased to 14.8% and 5.4% at 24 months, respectively. Switch/add-on OAD was associated with higher HbA1c and body mass index (BMI), baseline OAD being non-dipeptidyl peptidase-4 inhibitor (DPP-4i)/non-sodium glucose cotransporter-2 inhibitor (SGLT2i), diabetes complications, no comorbidities and consulting a diabetes specialist. The mean (SD) HbA1c (%) was 6.73 (0.85) at 24 months. Higher HbA1c, diabetes complications, cardiovascular disease, being employed, no hypertension and younger treating physician were associated with ≥2 OAD classes prescription or target HbA1c non-attainment at 24 months. OHA-Q subscale scores were significantly higher in patients achieving (vs not achieving) target HbA1c and in those continuing monotherapy (vs combination therapy). Baseline age (<65 years), sex (female), HbA1c, alcohol use, use of non-|DPP-4i OADs or non-T2DM drugs, diabetes complications and cardiovascular disease had a significant negative impact, while EuroQol five-dimensional five-level and Summary of Diabetes Self-Care Activities-specific diet scores, BMI and unemployment had a significant positive impact on OHA-Q scores at 24 months. CONCLUSIONS: Primary outcomes show real-world treatment patterns and glycemic control over 2 years in patients with T2DM newly initiated on OAD monotherapy in Japan. Key factors associated with durability of initial monotherapy, target achievement or treatment satisfaction included baseline HbA1c, comorbidity and initial OAD choice.

Diagnostic and therapeutic strategies for vestibular neuritis of the Japan society for equilibrium research.

OBJECTIVE: To provide diagnostic and therapeutic strategies for vestibular neuritis in accordance with the Japanese Clinical Practice Guidelines for Vestibular Neuritis 2021. METHODS: The Committee for Clinical Practice Guidelines for Vestibular Neuritis was entrusted with a review of the relevant scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment of vestibular neuritis were produced, and a search of the literature was conducted to identify studies related to the CQs. The recommendations were based on the literature review and the expert opinion of a subcommittee. RESULTS: We proposed the diagnostic criteria for vestibular neuritis, as well as answers to CQs, recommendations, and evidence levels for the treatment of vestibular neuritis. CONCLUSION: The diagnostic criteria for vestibular neuritis were based on clinical history and examination findings after completing the differential diagnosis process. The treatment of vestibular neuritis was divided into acute, subacute, and chronic stages. The Japanese Clinical Practice Guidelines for Vestibular Neuritis 2021 should be used as a reference in the diagnosis and treatment of vestibular neuritis.

Impact of heart rate on adverse events in patients with non-valvular atrial fibrillation: Subanalysis of the J-RHYTHM Registry.

Background: Although heart rate (HR) is reportedly associated with major cardiovascular outcomes in the general population, its impact on adverse events in patients with non-valvular atrial fibrillation (NVAF) remains controversial. Thus, we performed post hoc analyses of data from the J-RHYTHM Registry to clarify this in patients with NVAF. Results: Of 7406 outpatients with NVAF from 158 institutions, 6886 (age, 69.8 ± 9.9 years; men, 70.8%), in whom both baseline HR and HR-end (at the time closest to an event or at the last visit of follow-up) were measured during the two-year follow-up period or until the occurrence of an event, constituted the study group. The baseline HR and HR-end values were 72.5 ± 13.3 bpm and 73.3 ± 13.3 bpm, respectively. Thromboembolism, major hemorrhage, all-cause death, and cardiovascular death occurred in 117 (1.7%), 130 (1.9%), 157 (2.3%), and 58 (0.8%) patients, respectively. Baseline HR was not associated with any adverse event, whereas HR-end (per 1-bpm increase) was significantly associated with an increased incidence of all adverse events. Furthermore, the highest quartile of HR-end (≥80 bpm) was independently associated with the incidence of major hemorrhage (adjusted odds ratio [OR], 2.90; 95% confidence interval [CI], 1.69-4.96; P < 0.001), all-cause death (OR, 3.42; 95% CI, 1.99-5.88; P < 0.001), and cardiovascular death (OR, 5.07; 95% CI, 1.49-17.22; P = 0.009) compared with the second quartile (64-71 bpm), even after adjusting for known confounding factors, HR-controlling drug use, and systolic blood pressure-end. Conclusions: In patients with NVAF, HR-end was significantly associated with adverse events independent of systolic blood pressure-end, whereas baseline HR was not.

Impact of Systolic Blood Pressure Time in Target Range on Adverse Events in Patients With Nonvalvular Atrial Fibrillation (from the J-RHYTHM Registry).

Although time in target range (TTR) of systolic blood pressure (BP), an index of consistency of BP control, is reportedly associated with major cardiovascular outcomes, the impact of BP-TTR on adverse events in patients with nonvalvular atrial fibrillation (NVAF) has not been thoroughly investigated. Thus, we performed a post hoc analysis to clarify it in patients with NVAF using data of the J-RHYTHM registry. Of 7,406 outpatients with NVAF, 7,226 (age, 70 ± 10 years; men, 71%), in whom BP was measured 4 times or more (15 ± 5 times) during the 2-year follow-up period or until occurrence of an event, constituted the study group. Systolic BP-TTR, with a target range of 110 to 130 mm Hg, was calculated by Rosendaal linear interpolation method. Overall systolic BP-TTR was 50 ± 28%. Thromboembolism, major hemorrhage, all-cause death, and cardiovascular death occurred in 110 (1.5%), 121 (1.7%), 168 (2.3%), and 60 patients (0.8%), respectively. Each 1% increase in systolic BP-TTR was significantly associated with a decreased incidence of all adverse events in the unadjusted model; whereas, significant association was observed only for cardiovascular death (adjusted hazard ratio 0.983, 95% confidence interval 0.971 to 0.995, p = 0.006) after adjusting for known confounders and systolic BP at the time closest to an event. In contrast, each 1% increase in systolic BP time in subtarget range of <110 mm Hg was significantly associated with an increased risk of thromboembolism (hazard ratio 1.014, 95% confidence interval 1.005 to 1.024, p = 0.002). In conclusion, systolic BP-TTR and BP time in subtarget range would be useful for risk evaluation of cardiovascular death and thromboembolism, respectively, in patients with NVAF.

Clinical Status and Outcome of Isolated Right Ventricular Hypoplasia: A Systematic Review and Pooled Analysis of Case Reports.

Background: Isolated right ventricular hypoplasia (IRVH), not associated with severe pulmonary or tricuspid valve malformation, is a rare congenital myocardial disease. This study aims to evaluate the clinical status and outcome of IRVH. Methods: A systematic search of keywords on IRVH was conducted. Studies were searched from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) published between January 1950 and August 2021. Results: Thirty studies met the inclusion criteria. All of these studies were case reports and included 54 patients (25 males and 29 females). The median age of the patients was 2.5 years old (0-15.3 years). Of the 54 patients, 13 (24.1%) reported a family history of cardiomyopathy. Moreover, 50 (92.6%), 19 (35.2%), and 17 (31.5%) patients were diagnosed with cyanosis, finger clubbing, and dyspnea, respectively. Furthermore, 53 (98.2%) patients had a patent foramen ovale or an atrial septal defect (ASD). Z-score of the tricuspid valve diameter on echocardiogram was -2.16 ± 1.53, concomitant with small right ventricular end-diastolic volume. In addition, 29 (53.7%), 21 (38.9%), 7 (13.0%), and 2 (3.7%) patients underwent surgery, ASD closure, Glenn operation, and one and a half ventricular repair, respectively. Among them, nine (20.4%) patients expired, and the multivariable logistic regression analysis showed that infancy, heart failure, and higher right ventricular end-diastolic pressure were risk factors for death. Conclusions: IRVH was diagnosed early in children with cyanosis and was associated with high mortality. This systematic review and pooled analysis provided evidence to assess the of IRVH degree in order to evaluate the clinical status and outcome of IRVH.

Thromboembolic events in left ventricular non-compaction: comparison between children and adults - a systematic review and meta-analysis.

OBJECTIVE: Left ventricular non-compaction (LVNC) is morphologically characterised by excessive trabeculations and deep recesses in the ventricular wall. The risk of thromboembolic disease in the paediatric patients with LVNC has not been clearly established. We conducted this systematic review to evaluate the prevalence and incidence of thromboembolism (TE) in paediatric and adult patients with LVNC and searched for risk factors for TE to explore management strategies. METHODS: The primary outcome was the prevalence and incidence of TE in the patients with LVNC. The secondary outcome was the TE and mortality and heart transplantation rates between paediatric and adult patients with LVNC. We searched for studies published in MEDLINE, Embase and Cochrane Central Register of Controlled Trials between January 1950 and December 2020. A systematic search of keywords related to LVNC, anticoagulants/antiplatelets and TE was conducted. Studies that did not present original research, non-human studies, duplicated studies were excluded. RESULTS: Fifty-seven studies met the inclusion criteria. A total of 726 paediatric and 3862 adult patients were included. The mean prevalence rates of TE in the paediatric and adult patients with LVNC were 2.6% and 6.2% (I2=0%; p<0.450 and I2=73.7%; p<0.001), respectively. The mean annual incidences of TE in paediatric and adult patients with LVNC were 1.4% and 2.9% (I2=99.4%; p<0.001 and I2=99.5%; p<0.001), respectively. Multivariate logistic regression analysis showed that TE was associated with left ventricular ejection fraction in <40% of paediatric patients (OR, 9.47; 95% CI, 1.35 to 188.23; p=0.0225). CONCLUSIONS: The prevalence and incidence rates in paediatric patients were lower than those in adult patients. TE was associated with a reduced systolic function in paediatric patients with LVNC.

Fragmented QRS on electrocardiography as a predictor for diastolic cardiac dysfunction in type 2 diabetes.

AIMS/INTRODUCTION: Diastolic cardiac dysfunction in type 2 diabetes (DD2D) is a critical risk of heart failure with preserved ejection fraction. However, there is no established biomarker to detect DD2D. We aimed to investigate the predictive impact of fragmented QRS (fQRS) on electrocardiography on the existence of DD2D. MATERIALS AND METHODS: We included in-hospital patients with type 2 diabetes without heart failure symptoms who were admitted to our institution for glycemic management between November 2017 and April 2021. An fQRS was defined as an additional R' wave or notching/splitting of the S wave in two contiguous electrocardiography leads. DD2D was diagnosed according to the latest guidelines of the American Society of Echocardiography. RESULTS: Of 320 participants, 122 patients (38.1%) had fQRS. DD2D was diagnosed in 82 (25.6%). An fQRS was significantly associated with the existence of DD2D (odds ratio 4.37, 95% confidence interval 2.33-8.20; p < 0.0001) adjusted for seven potential confounders. The correlation between DD2D and diabetic microvascular disease was significant only among those with fQRS. Classification and regression tree analysis showed that fQRS was the most relevant optimum split for DD2D. CONCLUSIONS: An fQRS might be a simple and promising predictor of the existence of DD2D. The findings should be validated in a larger-scale cohort.

Catheter Ablation Energy Sources and Myocardial Injury and Coagulation Biomarkers During Uninterrupted Periprocedural Edoxaban Use　- A Subanalysis of KYU-RABLE.

BACKGROUND: The effects of catheter ablation (CA) energy sources on myocardial injury and coagulation biomarkers among Japanese non-valvular atrial fibrillation patients receiving uninterrupted periprocedural edoxaban are unclear. This KYU-RABLE exploratory subanalysis compared the effects of CA using radiofrequency energy vs. cryoballoon on: (1) myocardial injury; and (2) plasma edoxaban and coagulation biomarker concentrations measured before and after CA.Methods and Results:Plasma creatine kinase (CK), edoxaban, D-dimer, and prothrombin fragment 1+2 (F1+2) concentrations within 1 h before CA were compared with concentrations the day after. All biomarkers increased after CA, regardless of the energy source, but especially with cryoballoon. Significantly higher increases in CK concentrations from before to the day after CA were seen with cryoballoon compared with radiofrequency energy (P<0.0001). Edoxaban concentrations were similar in both groups. Concentrations of D-dimer and F1+2 increased in both groups, but were significantly higher in the cryoballoon group (P<0.0001 and P=0.006, respectively). There were no significant between-group differences in the incidence of thrombotic or bleeding events. CONCLUSIONS: Uninterrupted edoxaban concentrations were similar in both groups. Both myocardial injury and coagulation biomarkers increased after CA, especially with cryoballoon, but there was no difference in the incidence of thrombotic or bleeding events. These findings suggest the efficacy of uninterrupted edoxaban, regardless of the CA energy source. Periprocedural anticoagulation, particularly with cryoballoon, should be undertaken with care.

Clinical significance of chronic myocarditis: systematic review and meta-analysis.

Chronic myocarditis is a prolonged inflammatory condition in the myocardium and its histological manifestation is defined by the presence of an inflammatory infiltrate. Chronic myocarditis has not been well known and its treatment of chronic myocarditis has not been established. Primary outcome of this study was to assess the efficacy of immunomodulatory treatment in addition to conventional treatment, and secondary outcomes were to clarity the prognosis of natural history of chronic myocarditis and incidence of chronic myocarditis in patients with dilated cardiomyopathy (DCM). We searched for studies in Medline, Embase, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi published between January 1946 and June 2020. Sixteen studies met the inclusion criteria. A meta-analysis revealed that patients receiving immunomodulatory treatment showed an improvement in left ventricular ejection fraction after immunomodulatory treatment compared to the control group (hazard ratio, 16.65; confidence interval, 4.55-28.74; p = 0.007). Five-year survival rate of the patients with inflammatory DCM (iDCM) and DCM was 52.7-70.3% and 51.9-91.1%, respectively. Moreover, 51.5%-62.7% of patients with DCM met the criteria of iDCM. Our systematic review revealed that patients with chronic myocarditis had poor prognosis and immunomodulatory treatment was significantly effective in addition to conventional treatment.

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.