Dose Individualization of Cefepime for Febrile Neutropenia in Patients With Lymphoma or Multiple Myeloma: Implications for Therapeutic Drug Monitoring.

BACKGROUND: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma. METHODS: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours. Unbound concentrations were determined at 0.5 hours, 7.2 hours [at the 60% time point of the 12 hours administration interval (C7.2h)], and 11 hours (trough concentration) after the first infusion (rate: 2 g/h). The primary and secondary end points were the predictive performance of the area under the unbound concentration-time curve (AUC unbound ) and the effect of unbound cefepime pharmacokinetic parameters on clinical response, respectively. RESULTS: The mean (SD) AUC unbound was 689.7 (226.6) mcg h/mL, which correlated with C7.2h (R 2 = 0.90), and the Bayesian posterior AUC unbound using only the trough concentration (R 2 = 0.66). Although higher exposure was more likely to show a better clinical response, each parameter did not indicate a statistical significance between positive and negative clinical responses ( P = 0.0907 for creatinine clearance (Ccr), 0.2523 for C7.2h, 0.4079 for trough concentration, and 0.1142 for AUC unbound ). Cutoff values were calculated as 80.2 mL/min for Ccr (sensitivity: 0.889, specificity: 0.714), 18.6 mcg/mL for C7.2h (sensitivity: 0.571, specificity: 1.000), and 9.2 mcg/mL for trough concentration (sensitivity: 0.571, specificity: 1.000). When aiming for a time above 100% the minimum inhibitory concentration, both continuous infusion of 4 g/d and intermittent infusion of 2 g every 8 hours achieved a probability of approximately 100% at a minimum inhibitory concentration of 8 mcg/mL. CONCLUSIONS: Therapeutic drug monitoring by sampling at C7.2h or trough can facilitate rapid dose optimization. Continuous infusion of 4 g/d was recommended. Intermittent dosing of 2 g every 8 hours was alternatively suggested for patients with a Ccr of 60-90 mL/min.

Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-center Study.

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.

Triglyceride/high-density lipoprotein cholesterol ratio may be a better index of cardiometabolic risk in women than in men in Japan.

BACKGROUND AND AIMS: Few data exist regarding the gender differences in the relationship between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiometabolic risk leading to atherosclerotic cardiovascular disease (ASCVD). We investigated, by gender, the association between the TG/HDL-C ratio and metabolic syndrome (MetS) and its components in the Japanese, who are less obese than their Western counterparts. METHODS AND RESULTS: A population consisting of 10,373 participants (average age, 47.6 ± 12.6 years, 60.9 % men) at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020 was studied using a cross-sectional study method. The TG/HDL-C ratio and proportion of visceral obesity increased approximately parallelly with age in women; however, these parameters did not change proportionally with age in men. Accordingly, receiver operating characteristic analysis revealed the accuracy of the TG/HDL-C ratio as a predictor of visceral obesity based on the Japanese MetS criteria (women vs. men: area under the curve, 0.797 vs. 0.712, p < 0.0001; sensitivity, 82.4 % vs. 59.9 %; specificity, 61.1 % vs. 71.1 %; cutoff value, 1.075 vs. 1.933, respectively). Furthermore, a higher TG/HDL-C ratio in women reflected the status of MetS and its components compared with men in multi-logistic regression analysis. CONCLUSION: An increased TG/HDL-C ratio in women may be involved in MetS and its components compared to men. We may pay attention to visceral obesity and increased TG/HDL-C ratio to prevent ASCVD risk in women, even in the Japanese population, which generally contains a lower proportion of obesity than in Western populations.

Higher frequency of fish intake and healthy lifestyle behaviors may be associated with a lower platelet count in Japan: Implication for the anti-atherosclerotic effect of fish intake.

BACKGROUND: Habitual fish intake and healthier lifestyles are associated with a lower risk of atherosclerotic cardiovascular disease (ASCVD). Higher platelet counts (PLCs) are reportedly associated with higher ASCVD events. We aimed to investigate the association between fish intake and lifestyle with PLCs. METHODS: We conducted a cross-sectional study in a cohort of 9329 participants (average age: 46.9 ± 12.9 years; 58.9% men) with no history of ASCVD registered at the Health Planning Center of Nihon University Hospital in 2019. RESULTS: The average fish intake frequency was 2.15 ± 1.28 days/week. As fish intake frequency increased (0, 1, 2, 3, 4, 5, 6, and 7 days), PLC decreased significantly (p < 0.0001). Multivariable logistic regression analysis showed that higher fish intake frequency tended to be a determinant of lower PLC. Aerobic exercise habits and sleep duration were independent negative determinants of PLC. Cigarette smoking habits were a positive independent determinant of PLC. Furthermore, with increasing fish intake frequency, the proportion of participants with habitual aerobic exercise, non-smoking habits, and longer sleep duration increased (p < 0.0001 for all). Higher n-3 polyunsaturated fatty acid (n-3 PUFA), calculated based on data from the Japanese National Health and Nutrition Survey, intake was associated with a lower PLC. CONCLUSION: Higher fish intake and healthier lifestyle behaviors may be comprehensively associated with lower PLCs. The intake of N-3 PUFA with anti-inflammatory effects, rich in fish, may also be related to the lower PLC. This association may explain the preventive effects of fish intake on ASCVD risk.

Habitual fish consumption and healthy lifestyle behaviours may be associated with higher total serum bilirubin level and anti-inflammatory activity: a cross-sectional study.

Habitual fish consumption and a healthy lifestyle are associated with lower atherosclerotic CVD (ASCVD) risk. Mildly elevated bilirubin, an end product of Hb metabolism, may be associated with anti-inflammatory effects, suppressing ASCVD risk. No data exist on the relationship between fish consumption, total serum bilirubin (TSB) and inflammation in clinical settings. We conducted a cross-sectional study between April 2019 and March 2020 in a cohort of 8292 participants (average age, 46·7 (sd 12·9) years and 58·9 % men) with no history of ASCVD and TSB concentrations < 2·0 mg/dl. Multiple stepwise regression analysis showed Hb concentrations were a solid positive determinant of TSB concentrations (ß = 0·302, P< 0·0001). Fish consumption (ß = 0·025, P= 0·019) and aerobic exercise (ß = 0·021, P= 0·043) were statistically weak but significantly positive determinants of TSB concentrations. Cigarette smoking negatively affected TSB concentrations (ß = −0·104, P< 0·0001). Moreover, with increasing fish consumption, the proportion of participants with a habit of cigarette smoking decreased, and that of participants who engaged in aerobic exercises increased (P< 0·0001 for both). Furthermore, as TSB concentrations increased, the leukocyte counts and C-reactive protein concentrations decreased (P< 0·0001 for both). In conclusion, despite the lesser relevance given to TSB concentrations than Hb concentrations, higher fish consumption and healthier lifestyle behaviours related to fish consumption habits may be additively or synergistically associated with higher TSB concentrations and anti-inflammatory activity, leading to attenuated ASCVD risk. Further investigations are needed to clarify the causal relationships between these factors.

External Validation of the HELT-E2S2 Score in Japanese Patients With Nonvalvular Atrial Fibrillation　- A Pooled Analysis of the RAFFINE and SAKURA Registries.

BACKGROUND: The HELT-E2S2score, which assigns 1 point to Hypertension, Elderly aged 75-84 years, Low body mass index <18.5 kg/m2, and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.Methods and Results: We evaluated the prognostic performance of the HELT-E2S2score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E2S2score was 0.661 (95% confidence interval [CI], 0.629-0.692), which was numerically higher than with the CHADS2score (0.644, 95% CI 0.613-0.675; P=0.15 vs. HELT-E2S2) or CHA2DS2-VASc score (0.650, 95% CI, 0.619-0.680; P=0.37 vs. HELT-E2S2). In the SAKURA AF Registry, the C-statistic of the HELT-E2S2score was consistently higher than the CHADS2and CHA2DS2-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals. CONCLUSIONS: The HELT-E2S2score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS2or CHA2DS2-VASc scores may vary across different hospital settings.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Prognostic risk stratification based on left ventricular mechanical dyssynchrony in patients at low or intermediate risk of major cardiac events using the J-ACCESS risk model.

There have been no reports on prognostic prediction and risk stratification based on stress phase bandwidth (SPBW), or a left ventricular (LV) mechanical dyssynchrony index, in patients with known or suspected stable coronary artery disease (CAD) at low or intermediate risk of major cardiac events (MCEs) using the J-ACCESS risk model. We retrospectively investigated 4,996 consecutive patients with known or suspected CAD who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and followed up for 3 years to confirm their prognosis. MCE risk over 3 years was estimated using an equation based on that used in the J-ACCESS study. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), and severe heart failure requiring hospitalization. SPBW was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. Based on the estimated 3-year incidence of MCEs obtained from the J-ACCESS risk model, 4,123 of the 4,996 consecutive patients were classified as low (n = 2,653) or intermediate risk (n = 1,470) and they were analyzed for follow-up. During the follow-up, 153 patients experienced MCEs: cardiac death (n = 38), non-fatal MI (n = 45), and severe heart failure (n = 70). The results of the multivariate analysis showed age, estimated glomerular filtration rate (eGFR), stress LV ejection fraction, and stress SPBW to be independent predictors of MCEs. The actual 3-year MCE rate in patients at intermediate risk was significantly higher than in those at low risk (6.7% vs. 2.1%, P < 0.0001). However, the actual 3-year MCE rate in patients with abnormal SPBW (> 38°) was 4.0% and 9.2% in low- and intermediate-risk patients, respectively, which corresponded to intermediate and high risk. Kaplan-Meier analysis also showed significant risk stratification by normal SPBW values for both low- and intermediate-risk patients. LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for risk stratification of known or suspected stable CAD patients at low or intermediate risk of MCEs and may help identify higher risk patients who could not be identified as being at risk based on J-ACCESS risk assessment.

Impact of the COVID-19 pandemic on the hospitalizations, time course, presenting symptoms, and mid-term outcomes in patients with myocardial infarctions in a Japanese multi-center registry.

To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on myocardial infarctions (MIs), consecutive MI patients were retrospectively reviewed in a multi-center registry. The patient characteristics and 180-day mortality for both ST-segment elevation myocardial infarctions (STEMIs) and non-STEMIs (NSTEMIs) in the after-pandemic period (7 April 2020-6 April 2021) were compared to the pre-pandemic period (7 April 2019-6 April 2020). Inpatients with MIs, STEMIs, and NSTEMIs decreased by 9.5%, 12.5%, and 4.1% in the after-pandemic period. The type of the presenting symptoms (as classified as typical symptoms, atypical symptoms, and out-of-hospital cardiac arrests [OHCAs]) did not differ between the two time periods for both STEMIs and NSTEMIs, while the rate of OHCAs was numerically higher in the after-pandemic period for the STEMIs (12.1% vs. 8.0%, p = 0.30). The symptom-to-admission time (STAT) did not differ between the two time periods for both STEMIs and NSTEMIs, but the door-to-balloon time (DTBT) for STEMIs was significantly longer in the after-pandemic period (83.0 [67.0-100.7] min vs. 70.0 [59.0-88.7] min, p = 0.004). The 180-day mortality did not significantly differ between the two time periods for both STEMIs (15.9% vs. 11.4%, p = 0.14) and NSTEMIs (9.9% vs. 8.0%, p = 0.59). In conclusion, hospitalizations for MIs decreased after the COVID-19 pandemic. Although the DTBTs were significantly longer in the after-pandemic period, the mid-term outcomes for MIs were preserved.

Edoxaban Monotherapy in Nonvalvular Atrial Fibrillation Patients with Coronary Artery Disease.

Background: Current guidelines recommend an oral anticoagulant (OAC) monotherapy in patients with nonvalvular atrial fibrillation (NVAF) and stable coronary artery disease (CAD) 1 year postpercutaneous coronary intervention (PCI). It might be possible to shorten the time for de-escalation from a dual therapy to monotherapy, but data regarding de-escalation to an edoxaban monotherapy are lacking. This study aimed to assess the clinical safety of an edoxaban monotherapy in patients with NVAF and stable CAD. Methods: A multicenter, prospective, randomized, open-label, and parallel group study was established to investigate the safety of an edoxaban monotherapy in patients with NVAF and stable CAD including over 6 months postimplantation of a third-generation DES and 1 year postimplantation of other stents (PRAEDO AF study). Between March 2018 and June 2020, 147 patients from 8 institutions in Japan were randomized to receive either an edoxaban monotherapy (n = 74) or combination therapy (edoxaban plus clopidogrel, n = 73). The primary study endpoint was the composite incidence of major bleeding and clinically significant bleeding, defined according to the ISTH criteria. Results: Major or clinically significant bleeding occurred in 2 patients in the monotherapy group (1.67% per patient-year) and in 5 patients in the combination therapy group (4.28% per patient-year) (hazard ratio, 0.39; 95% confidence interval, 0.08-2.02). There was no incidence of a myocardial infarction, stent thrombosis, unstable angina requiring revascularization, ischemic stroke, systemic stroke, or hemorrhagic stroke in either of the groups. Conclusions: The edoxaban monotherapy was shown to have acceptable clinical safety in patients with NVAF and stable CAD. The study was registered with the Japan Registry of Clinical Trials (jRCTs031180119).

Inadequate sleep duration may attenuate the anti-inflammatory effects of fish consumption in a healthy Japanese population: a cross-sectional study.

High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration (ß = 0·084, P < 0·0001). Additionally, habitual aerobic exercise (ß = 0·059, P < 0·0001) or cigarette smoking (ß = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) (ß = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count (ß = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6­7 h of sleep as the low value (P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors.

Health economics-based verification of functional myocardial ischemia evaluation of stable coronary artery disease in Japan: A long-term longitudinal study using propensity score matching.

BACKGROUND: The procedural numbers and medical costs of percutaneous coronary intervention (PCI), mainly elective PCI, have been increasing in Japan. Owing to increased interest in the appropriateness of coronary revascularization, we conducted this medical economics-based evaluation of testing and diagnosis of stable coronary artery disease (CAD). METHODS AND RESULTS: We reviewed patients' medical insurance data to identify stable CAD patients who underwent coronary computed tomography angiography, cardiac single-photon emission computed tomography, coronary angiography, or fractional flow reserve. Subjects were divided into anatomical and functional evaluation groups according to the modality of testing, and background factors were matched by propensity score. The endpoints were major adverse cardiovascular events (MACE), life years (LYs), medical costs, and cost-effectiveness analysis (CEA). The observations were performed for 36 months. MACE, medical costs, and CEA of the functional group in the overall category were trending to be better than the anatomical group (MACE, P = .051; medical costs: 3,105 US$ vs 4,430 US$, P = .007; CEA: 2,431 US$/LY vs 2,902 US$/LY, P = .043). CONCLUSIONS: The functional evaluation approach improved long-term clinical outcomes and reduced cumulative medical costs. As a result, the modality composition of functional myocardial ischemia evaluation was demonstrated to offer superior cost-effectiveness in stable CAD.

Clinical Utility of a Slow 201Tl Washout Rate in the Detection of Multi-Vessel Coronary Artery Disease Using a Simultaneous Acquisition Rest 99 mTc/Stress 201Tl Protocol and a Semiconducting Gamma Camera.

BACKGROUND: The diagnostic accuracy of stress myocardial perfusion single-photon emission computed tomography (SPECT) to detect coronary artery disease (CAD) is reduced by the balanced reduction of myocardial perfusion in patients with multi-vessel or left main trunk CAD (multi-vessel group). This study investigated the diagnostic performance of a simultaneous acquisition rest 99 mTc/stress 201Tl dual-isotope protocol for myocardial perfusion SPECT (MPS) in a multi-vessel group by examining the assessment of a slow 201Tl washout rate (WR) finding in comparison to the accuracy of perfusion assessments.Methods and Results: This study enrolled 91 patients who had undergone angiography within 3 months after MPS. The diagnostic performances of perfusion assessments and a slow 201Tl WR parameter were compared using the area under the curve (AUC) in a multi-vessel group of patients with mild ischemia (2≤summed difference score [SDS]≤7). The AUC of a slow WR parameter was significantly larger compared with that for perfusion assessments, in patients with mild ischemia, (AUC, 0.736 vs. 0.504-0.558, P value: <0.01-0.05). CONCLUSIONS: Among patients with mild ischemia, a slow 201Tl WR parameter improved the detection of CAD in a multi-vessel group.

Different Determinants of the Recurrence of Atrial Fibrillation and Adverse Clinical Events in the Mid-Term Period After Atrial Fibrillation Ablation.

BACKGROUND: It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation.Methods and Results:We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences. CONCLUSIONS: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Assessment of sex differences in associations between sleep duration and lipid/glucose metabolism in urban Japan: a cross-sectional study.

Inadequate sleep durations (short or long) are related to worsening of lipid/glucose metabolism, leading to atherosclerotic cardiovascular diseases (ASCVD). Few data exist on sex differences in this relationship that, to date, has been scarcely reported. This cross-sectional study included 6678 men and 4700 women at the Health Planning Center of Nihon University Hospital, located in the center of Tokyo, between September 2015 and October 2016. The prevalence of diabetes and dyslipidemia in the participants was 3.3% and 6.5%, respectively. Sleep duration was divided into five categories: < 5 h, 5-6 h, 6-7 h, 7-8 h, and ≥ 8 h. We examined the odds ratio (OR) and 95% confidence interval (CI) of lipid/glucose metabolism-related markers for the reference value defined in each guideline with 6-7 h as the reference of comparison. In men, a sleep duration of < 5 h was associated with ORs of 1.32 and 1.33 (95% CI, 1.01-1.73 and 1.02-1.74) for LDL-C level ≥ 120 mg/dL and non-HDL-C level of ≥ 150 mg/dL (defined as "borderline hyper" by the Japan Atherosclerosis Society Guidelines for Prevention of ASCVD 2017), respectively. Moreover, a sleep duration of < 5 h was associated with an OR of 1.77 (1.33-2.35) for fasting blood glucose of ≥ 100 mg/dL (defined as "high" by a specialized lifestyle checkup program in Japan). In women, sleep duration of < 5 h was associated with an OR of 1.70 (1.24-2.33) for HbA1c level of ≥ 5.6% (defined as "high" by a specialized life style checkup program in Japan). However, there was no association between sleep duration and serum lipid profile. Inadequate short sleep duration was as a potential risk factor of adverse lipid and/or glucose metabolism in both sexes. However, there were sex differences in associations between sleep duration and lipid/glucose metabolism in urban Japan. To further reduce risks of ASCVD, it is of particular importance to emphasize adequate sleep duration in both sexes.Trial registration UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000037643 retrospectively registered on August 9, 2019.

Prognostic value of the normalization of left ventricular mechanical dyssynchrony after revascularization in patients with coronary artery disease.

There are no reports indicating a prognostic difference based on normalization of left ventricular (LV) mechanical dyssynchrony after revascularization in patients with coronary artery disease (CAD). We retrospectively investigated 596 patients who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging. All patients had significant stenosis with ≥ 75% narrowing of the coronary arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia by the SPECT. Patients underwent revascularization and thereafter were re-evaluated by the SPECT during a chronic phase, and followed-up to confirm their prognosis for ≥ 1 year. The composite endpoint was the onset of major cardiac events (MCEs) consisting of cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (UAP), and severe heart failure requiring hospitalization. The stress phase bandwidth (SPBW) was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. During the follow-up, 64 patients experienced MCEs: Cardiac death (n = 11), non-fatal MI (n = 5), UAP (n = 26), and severe heart failure (n = 22). The results of the multivariate analysis showed the ∆summed difference score %, ∆stress LV ejection fraction, and stress SPBW after revascularization to be independent predictors of MCEs. Additionally, the results of the multivariate logistic regression analysis showed the summed rest score%, summed difference score%, stress LV ejection fraction, and perfusion defects in the left circumflex artery region before revascularization to be independent predictors for normalized SPBW after revascularization. The prognosis of patients who normalized SPBW after revascularization was similar to that of patients with a normal SPBW before revascularization, while patients who did not normalize after revascularization had the worst prognosis. In conclusion, normalization of LV dyssynchrony after revascularization assessed with nuclear cardiology may help predict future MCEs and thus a useful indicator for predicting improved prognosis in patients with CAD.

Clinical outcomes for intracoronary imaging strategies at different medical facilities in Japanese patients with coronary artery disease: the SAKURA imaging PCI Registry.

The relationships between intracoronary imaging modalities and outcomes among Japanese patients with coronary artery disease (CAD) based on the type of medical facility providing outpatient care remain unclear. In this multicenter prospective study (SAKURA PCI Registry), we aimed to investigate the clinical outcomes of patients with CAD who underwent percutaneous coronary intervention (PCI) between April 2015 and December 2018. In this registry, we investigated differences in patient characteristics, intracoronary imaging modalities, and clinical outcomes between two types of medical facilities. Of the 414 patients enrolled in this registry, 196 were treated at two university hospitals, and 218 were treated at five community hospitals (median follow-up 11.0 months). The primary endpoint was clinically relevant events (CREs), including a composite of all-cause death, non-fatal myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, stroke, and major bleeding. Patients treated at university hospitals had higher rates of diabetes (50% vs. 38%, p = 0.015) and malignant tumors (12% vs. 6%, p = 0.015) and more frequent use of multiple intracoronary imaging modalities than patients treated at community hospitals (21% vs. 0.5%, p < 0.001). The Kaplan-Meier incidence of CREs at 1 year was comparable between university hospitals and community hospitals (8.8% vs. 7.3%, p = 0.527, log-rank test). Despite the relatively higher risk among patients in university hospitals with frequent use of multi-intracoronary imaging modalities, adverse clinical events appeared to be comparable between patients with CAD treated at university and community hospitals in Japan.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Combined Higher Frequency Fish Consumption and Healthy Lifestyle May Lower the Triglyceride/HDL-C Ratio in Middle-Aged Japanese Males: Anti-Atherosclerotic Effect of Fish Consumption.

BACKGROUND: Fish consumption may be associated with a low risk of coronary artery disease. We aimed to investigate whether higher fish consumption results in improved lifestyle behaviors and thus lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio - a predictor of atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This cross-sectional study included 2,947 middle-aged Japanese males with no history of ASCVD or lipid-modifying therapy, who presented at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. We performed an analysis of variance using fish consumption as a categorical variable (0-2 days, 3-4 days, or 5-7 days per week). The serum TG/HDL-C ratio in the 5-7 days fish consumption group was significantly lower than those in the 0-2 and 3-4 days fish consumption groups (p < 0.0001 and p < 0.01, respectively). Multiple regression stepwise analysis revealed that weekly fish consumption negatively and independently determined the TG/HDL-C ratio (ß = -0.061, p = 0.001). As fish consumption increased, the proportion of subjects with smoking habits decreased (p = 0.014), those engaging in aerobic exercises and aggressive daily physical activity increased (p < 0.0001 for both), and those with alcohol habit increased (p < 0.0001). In addition, we developed the risk stratification for ASCVD by combining the serum HDL-C level and the serum TG/HDL-C ratio with fish consumption. CONCLUSION: Increased frequency of fish consumption and improved lifestyle behaviors due to daily fish intake may work additively to lower the serum TG/HDL-C ratio. These associations may explain why high fish consumption is associated with a lower risk of ASCVD. Our findings may help physicians and nutritionists in treating patients with heart diseases and metabolic conditions by recommending a high fish diet in middle-aged Japanese males.

Effect of Atorvastatin on Microcirculation Evaluated by Vascular Occlusion Test with Peripheral Near-Infrared Spectroscopy.

The vascular occlusion test (VOT) with peripheral near-infrared spectroscopy (NIRS) is a non-invasive method to evaluate peripheral microcirculation. Statin therapy is widely used for patients with dyslipidaemia and contributes to reducing low-density lipoprotein cholesterol (LDL-C) levels and adverse cardiovascular events. However, it is not yet clear whether statin treatment improves peripheral microcirculation assessed by VOT with NIRS. In the present study, using VOT with NIRS, we evaluated the effect of statin therapy on peripheral microcirculation in patients with dyslipidaemia before and after statin therapy. METHODS: A total of six consecutive patients with dyslipidaemia who had not received statin therapy (6 males, mean age 71.8 ± 7.4 years) were enrolled. All patients were administered atorvastatin and their peripheral microcirculation assessed using VOT with NIRS (NIRO-200NX, Hamamatsu Photonics K.K., Japan) before and after statin therapy. The NIRS probe was attached to the right thenar eminence and brachial artery blood flow was blocked for 3 min at 50 mmHg above the resting systolic blood pressure. Maximum and minimum values of NIRS parameters after the VOT were used to determine concentration changes for total haemoglobin (ΔcHb), oxyhaemoglobin (ΔO2Hb), deoxyhaemoglobin (ΔHHb), and tissue oxygenation index (ΔTOI). RESULTS: During the follow-up period (mean 30.3 ± 6.5 days), LDL-C level decreased from 129.7 ± 26.3 to 67.5 ± 20.2 mg/dL (p-value = 0.031), ΔTOI increased from 24.0 ± 5.3 to 33.7 ± 6.3% (p-value = 0.023), and ΔO2Hb increased from 16.4 ± 5.3 to 20.0 ± 6.6 µmol/L (p-value = 0.007). ΔcHb and ΔHHb did not change significantly. CONCLUSION: ΔO2Hb and ΔTOI were significantly increased during the follow-up period. These findings suggest that ΔO2Hb and ΔTOI could assess the improvement of peripheral microcirculation by statin therapy. Compared to ΔTOI, ΔO2Hb seems to be a more useful parameter to evaluate peripheral microcirculation.