Conduction System Pacing Upgrade in Chronic Heart Failure with Severe Left Ventricular Dysfunction and Chronic Atrial Fibrillation.

Cardiac resynchronization therapy (CRT) is a standard treatment for patients with severe congestive heart failure. However, one-third of patients receiving CRT are non-responders. Conduction system pacing (CSP), including His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has become an alternative to CRT therapy. Furthermore, CRT therapy with CSP has shown to be more effective than CRT alone. When an implantable cardiac defibrillator or CRT-defibrillator is implanted with CSP, the problem of which port the HBP lead and LBBAP lead should be connected to arises. We report 2 cases of upgrading to CRT with CSP by utilizing the atrial ports for HBP and LBBAP leads. The procedure is a simple, reasonable, and effective therapy for end-stage heart failure.

Cardiac Rehabilitation for Patients With Stable Ischemic Heart Disease Without Revascularization　- Rationale and Design of a Single-Arm Pilot Study.

Background: Clinical practice guidelines strongly recommend optimal medical therapy (OMT), including lifestyle modification, pharmacotherapy, and exercise-based cardiac rehabilitation (CR), in patients with stable ischemic heart disease (SIHD). However, the efficacy and safety of CR in patients with SIHD without revascularization remain unclear. Methods and Results: The Prospective Registry of STable Angina RehabiliTation (Pre-START) study is a multicenter, prospective, single-arm, open-label pilot study to evaluate the efficacy and safety of CR on health-related quality of life (HRQL), exercise capacity, and clinical outcomes in Japanese patients with SIHD without revascularization. In this study, all patients will undergo guideline-based OMT and are encouraged to have 36 outpatient CR sessions within 5 months after enrollment. The primary endpoint is the change in the Seattle Angina Questionnaire-7 summary score between baseline and the 6-month visit; an improvement of ≥5 points will be defined as a clinically important change. Secondary endpoints include changes in other HRQL scores and exercise capacity between baseline and the 6-month visit, as well as clinical outcomes between enrollment and the 6-month visit. Conclusions: The Pre-START study will provide valuable evidence to elucidate the efficacy and safety of CR in patients with SIHD and indispensable information for a subsequent randomized controlled trial. The study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000045415) on April 1, 2022.

Impact of Frailty and Age on Clinical Outcomes in Patients Who Underwent Endovascular Therapy.

PURPOSE: Information on the relationship between frailty and the outcome of endovascular therapy (EVT) in elderly patients with lower extremity peripheral artery disease (PAD) is scarce. This study aimed to reveal the impact of frailty on the prognosis of super-elderly patients who underwent EVT. MATERIALS AND METHODS: From August 2015 to August 2016, 335 consecutive patients who underwent EVT were enrolled in the I-PAD registry from 7 institutes in Nagano prefecture. Among them, we categorized 323 patients into 4 groups according to age and the presence or absence of frailty as follows: elderly with frailty (age ≥ 75, Clinical Frailty Scale [CFS] ≥ 5), elderly without frailty (age ≥ 75, CFS ≤ 4), young with frailty (age < 75, CFS ≥ 5), and young without frailty (age < 75, CFS ≤ 4); we analyzed them accordingly. The primary endpoints were major adverse cardiovascular and limb events (MACLE), defined as a composite of cardiovascular death, myocardial infarction, stroke, admission for heart failure, major amputation, and revascularization. The secondary endpoint was cardiovascular death. RESULTS: The median follow-up period was 2.7 years. In the elderly with frailty, elderly without frailty, young with frailty, and young without frailty groups, the freedom rates from MACLE were 34.9%, 55.7%, 35.4%, and 63.0%, respectively (p<0.001) and from all-cause death were 43.5%, 73.4%, 50.7%, and 90.9%, respectively (p<0.001). The freedom rates from MACLE were significantly higher among elderly patients with frailty than among young patients without frailty (55.7% vs 35.4%, p=0.01). In multivariate analysis, frailty was independently associated with MACLE incidence. CONCLUSION: Frailty as defined by CFS might be a predictor of MACLE incidence in patients with PAD who underwent EVT. By considering treatment indications for patients with PAD by focusing on frailty rather than age, we may examine whether EVT policies are appropriate and manage patient and caregiver expectations for potential improvement in functional outcomes. Further studies are expected to investigate whether changes in frailty after EVT change prognosis.

Body composition and mortality in patients undergoing endovascular treatment for peripheral artery disease.

An inverse correlation between body mass index and mortality in patients with peripheral artery disease (PAD) has been reported. However, little information is available regarding the impact of body composition on the clinical outcomes in patients with PAD. This study evaluated the relationships between the lean body mass index (LBMI), body fat % (BF%), and mortality and major amputation rate in patients with PAD. We evaluated 320 patients with PAD after endovascular treatment (EVT) enrolled from August 2015 to July 2016 and divided them into low and high LBMI and BF% groups based on their median values (17.47 kg/m2 and 22.07%, respectively). We assessed 3-year mortality and major amputation for the following patient groups: Low LBMI/Low BF%, Low LBMI/High BF%, High LBMI/Low BF%, and High LBMI/High BF%. During the median 3.1-year follow-up period, 70 (21.9%) patients died and 9 (2.9%) patients experienced major amputation. The survival rate was lower in the Low LBMI than in the High LBMI group, and was not significantly different between the Low and High BF% groups. Survival rates were lowest in the Low LBMI/Low BF% group (57.5%) and highest in the High LBMI/High BF% group (94.4%). There were no significant differences in major amputation rate between the Low LBMI and High LBMI groups, and between the Low BF% and High BF% groups. The Low LBMI and Low BF% groups were associated with an increased risk of mortality after adjustment for age, sex, frailty and conventional risk factors [hazard ratio (HR): 4.02; 95% confidence interval (CI) 2.10-7.70; p < 0.001 and HR: 4.48; 95% CI 1.58-12.68, p = 0.005, respectively], for age, sex, hemodialysis, and prior cerebral cardiovascular disease (HR: 3.63; 95% CI 1.93-6.82; p < 0.001 and HR: 4.03; 95% CI 1.43-11.42, p = 0.009, respectively) and for age, sex, and laboratory date (HR: 3.97; 95% CI 1.88-8.37; p < 0.001 and HR: 3.31; 95% CI 1.15-9.53, p = 0.026, respectively). In conclusion, Low LBMI and Low BF% were associated with poor prognosis in patients undergoing EVT for PAD, and mortality was the lowest in the High LBMI/High BF% group compared with other body composition groups.

Prognostic ability of mid-term worsening renal function after percutaneous coronary intervention: findings from the SHINANO registry.

Chronic kidney disease is a prognostic factor for cardiovascular disease. Worsening renal function (WRF), specifically, is an important predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). We evaluate the prognostic impact of mid-term WRF after PCI on future cardiovascular events. We examined the renal function data of 1086 patients in the first year after PCI using the SHINANO 5-year registry. Patients were divided into two groups, mid-term WRF and non-mid-term WRF, and primary outcomes were major adverse cardiovascular events (MACE) and death. Mid-term WRF was defined as an increase in creatinine (≥ 0.3 mg/dL) in the first year after PCI. Mid-term WRF was found in 101 patients (9.3%), and compared to non-mid-term WRF, it significantly increased the incidence of MACE (p < 0.001), and all-cause death (p < 0.001), myocardial infarction (p = 0.001). Furthermore, mid-term WRF patients had higher incidence of future heart failure (p < 0.001) and new-onset atrial fibrillation (p = 0.01). Patients with both mid-term WRF and chronic kidney disease had increased MACE compared to patients with either condition alone (p < 0.001). Similarly, patients with mid-term WRF and acute kidney injury had increased MACE compared to patients with either condition alone (p < 0.001). Multivariate Cox regression analysis revealed mid-term WRF as a strong predictor of MACE (hazard ratio: 2.50, 95% confidence interval 1.57-3.98, p < 0.001). Mid-term WRF after PCI negatively affects MACE, as well as future admission due to heart failure and new-onset atrial fibrillation, chronic kidney disease, and acute kidney injury.

Association of the Prognosis of Ankle-brachial Index Improvement One Year Following Endovascular Therapy in Patients with Peripheral Artery Disease: Data from the I-PAD NAGANO Registry.

Objective Despite reports on the effects of ankle-brachial index (ABI) improvement following endovascular therapy (EVT) on the limb prognosis, studies evaluating cardiovascular events are limited. We investigated whether or not ABI improvement 1 year following EVT was associated with cardiovascular events. Methods The I-PAD NAGANO registry is an observational multicenter cohort study that enrolled 337 patients with peripheral artery disease (PAD) who underwent EVT between August 2015 and July 2016. From this cohort, we identified 232 patients whose ABI data 1 year following EVT were available, after excluding patients with critical limb ischemia. We divided the patients into two groups according to the degree of ABI improvement 1 year following EVT (ΔABI) - the ΔABI <0.15 group and the ΔABI ≥0.15 group - and compared the outcomes. The primary endpoint was major adverse cardiovascular events (MACEs), including all - cause death, myocardial infarction (MI), and stroke. The secondary endpoints were major adverse limb events (MALEs), defined as a composite of target lesion revascularization and major amputation, all - cause death, MI, and stroke. The median follow-up period was 3.3 years. Results The incidence of MACEs was significantly higher in the ΔABI <0.15 group than in the ΔABI ≥0.15 group (ΔABI <0.15 vs. ΔABI ≥0.15, 25.8% vs. 11.9%, log-rank p=0.036), as was the incidence of stroke (14.1% vs. 2.2%, log-rank p=0.016). A Cox regression analysis revealed that ΔABI ≥0.15 was significantly associated with fewer MACEs (hazard ratio 0.38, 95% confidence interval 0.17-0.83, p=0.016). Conclusion An increase in ABI ≥0.15 at 1 year following EVT was a predictor of reduced MACEs.

Flat-Band in Pyrochlore Oxides: A First-Principles Study.

Using a first-principles electronic band calculation, we obtained a quasi flat-band near the Fermi level for the six pyrochlore oxides, A2B2O7. These quasi flat-bands are mostly characterized by the s-orbitals of the A-site. The band structures of these oxides are well described by the non-interacting Mielke model. Spin-polarized calculations showed that the ground state of these compounds was ferromagnetic after appropriate carrier doping, despite the absence of the magnetic element.

Development of Genome-Wide SNP Markers for Barley via Reference- Based RNA-Seq Analysis.

Marker-assisted selection of crop plants requires DNA markers that can distinguish between the closely related strains often used in breeding. The availability of reference genome sequence facilitates the generation of markers, by elucidating the genomic positions of new markers as well as of their neighboring sequences. In 2017, a high quality genome sequence was released for the six-row barley (Hordeum vulgare) cultivar Morex. Here, we developed a de novo RNA-Seq-based genotyping procedure for barley strains used in Japanese breeding programs. Using RNA samples from the seedling shoot, seedling root, and immature flower spike, we mapped next-generation sequencing reads onto the transcribed regions, which correspond to ∼590 Mb of the whole ∼4.8-Gbp reference genome sequence. Using 150 samples from 108 strains, we detected 181,567 SNPs and 45,135 indels located in the 28,939 transcribed regions distributed throughout the Morex genome. We evaluated the quality of this polymorphism detection approach by analyzing 387 RNA-Seq-derived SNPs using amplicon sequencing. More than 85% of the RNA-Seq SNPs were validated using the highly redundant reads from the amplicon sequencing, although half of the indels and multiple-allele loci showed different polymorphisms between the platforms. These results demonstrated that our RNA-Seq-based de novo polymorphism detection system generates genome-wide markers, even in the closely related barley genotypes used in breeding programs.

Effects of Whole Grain Wheat Bread on Visceral Fat Obesity in Japanese Subjects: A Randomized Double-Blind Study.

Metabolic syndrome is a risk factor for cardiovascular diseases and has become increasingly common in Japan. Epidemiological studies show inverse associations between intake of whole wheat grains and metabolic syndrome, but few dietary intervention trials have investigated the effect of whole wheat grain consumption. It was investigated whether a diet in which refined wheat bread (RW diet) was substituted by whole grain wheat bread (WW diet) would reduce visceral fat obesity in Japanese subjects. A randomized double-blind placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥ 23 kg/m2. Subjects were randomly assigned WW (WW group) or RW diets (RW group) for 12 weeks. Blood samples and computed tomography scans were obtained every 6th week. The WW group showed decrease (-4 cm2) in visceral fat area (VFA) (p < 0.05), whereas the RW group showed no significant changes. These time-dependent changes were significantly different between the groups. WW diet led to significant and safe reductions in VFA in subjects with BMI ≥ 23 kg/m2. WW diet may contribute to preventing visceral fat obesity.

Effects of high ß-glucan barley on visceral fat obesity in Japanese individuals: A randomized, double-blind study.

OBJECTIVE: The aim of this study was to investigate whether a diet in which high ß-glucan barley was substituted for rice would reduce visceral fat obesity in Japanese individuals. METHODS: A randomized, double-blind, placebo-controlled intervention study was conducted with 100 Japanese individuals with waist circumference (WC) ≥85 cm for men or ≥90 cm for women and body mass index (BMI) ≥24 kg/m2. Participants were randomly assigned to consume a mixture of rice and either high ß-glucan barley (test group, 4.4 g/d) or ß-glucan-free barley (placebo group) for 12 wk. Blood samples and computed tomography scans were obtained before and after the trial. RESULTS: Both groups showed decreases in body weight and BMI, and these changes were significantly greater in the test group. WC and visceral fat area (VFA) significantly decreased in both groups (VFA: -10.7 cm2 in the test group; -6.8 cm2 in the placebo group). These changes did not differ significantly between the groups. However, a subgroup analysis of participants with VFA ≥100 cm2 showed a significant decrease in the test group, and this decrease was significantly greater than in the placebo group. CONCLUSIONS: The intake of high ß-glucan barley led to significant and safe reductions in VFA, body weight, BMI, and WC in individuals with visceral fat obesity with VFA ≥100 cm2. Barley high in ß-glucan may contribute to preventing visceral fat obesity.

[Hybrid Coronary Revascularization of Minimally Invasive Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention in a Patient with Left Main Coronary Stenosis].

We report a successful case of hybrid coronary revascularization of minimally invasive coronary artery bypass grafting( MICS-CABG) and percutaneous coronary intervention(PCI). The patient was a 78-year-old man with angina pectoris due to left main trunk (LMT) lesion, and had a history of repeated PCI to the left anterior descending artery (LAD) and the left circumflex artery (LCX) for angina pectoris. He presented with a chest pain on effort in June, 2015. A coronary angiogram showed a severe stenosis in the LMT extending to LAD and LCX. We performed hybrid therapy of CABG to LAD, and PCI to LMT and the proximal portion of LCX because the lesion was technically and suitable for PCI. CABG to LAD was performed via left mini thoracotomy using the left inter mammary artery (LIMA). LIMA was harvested under 3-dimentional endoscope. On the 5th post-operative day, PCI was performed to LMT and LCX. The postoperative course was uneventful and he was discharged on the 11th post-operative day. This case suggests that hybrid coronary revascularization is less invasive and feasible for selected patients with multi-vessel disease.

Enhancement of ferromagnetism by oxygen isotope substitution in strontium ruthenate SrRuO3.

The oxygen isotope effect of the ferromagnetic transition in itinerant ferromagnet strontium ruthenate SrRuO3 with a Curie temperature Tc of 160 K is studied. We observed for the first time a shift of ∆Tc ~ 1 K by oxygen isotope substitution of 16O → 18O in SrRuO3 by precise measurements of DC and AC magnetizations. The results surprisingly lead to the noteworthy inverse isotope effect with negative coefficient α = -∂ lnTc/∂ lnM. The Raman spectra indicate that the main vibration frequency of 16O at 363 cm-1 shifts to 341 cm-1 following oxygen isotope substitution 18O. This shift is remarkably consistent with the Debye frequency being proportional to ∝ 1√M where M is the mass of an oxygen atom. The positive isotope shift of ∆Tc can be understood by taking account of the electron-phonon interaction.

Large enhancement of superconducting transition temperature of SrBi3 induced by Na substitution for Sr.

The Matthias rule, which is an empirical correlation between the superconducting transition temperature (Tc) and the average number of valence electrons per atom (n) in alloys and intermetallic compounds, has been used in the past as a guiding principle to search for new superconductors with higher Tc. The intermetallic compound SrBi3 (AuCu3 structure) exhibits a Tc of 5.6 K. An ab-initio electronic band structure calculation for SrBi3 predicted that Tc increases on decreasing the Fermi energy, i.e., on decreasing n, because of a steep increase in the density of states. In this study, we demonstrated that high-pressure (~ 3 GPa) and low-temperature ( < 350 °C) synthesis conditions enables the substitution of Na for about 40 at.% of Sr. With a consequent decrease in n, the Tc of (Sr,Na)Bi3 increases to 9.0 K. A new high-Tc peak is observed in the oscillatory dependence of Tc on n in compounds with the AuCu3 structure. We have shown that the oscillatory dependence of Tc is in good agreement with the band structure calculation. Our experiments reaffirm the importance of controlling the number of electrons in intermetallic compounds.

Radical scavenging reaction kinetics with multiwalled carbon nanotubes.

Progress in the development of carbon nanotubes (CNTs) has stimulated great interest among industries providing new applications. Meanwhile, toxicological evaluations on nanomaterials are advancing leading to a predictive exposure limit for CNTs, which implies the possibility of designing safer CNTs. To pursue safety by design, the redox potential in reactions with CNTs has been contemplated recently. However, the chemical reactivity of CNTs has not been explored kinetically, so that there is no scheme to express a redox reaction with CNTs, though it has been investigated and reported. In addition, the reactivity of CNTs is discussed with regard to impurities that consist of transition metals in CNTs, which obfuscates the contribution of CNTs to the reaction. The present work aimed at modeling CNT scavenging in aqueous solution using a kinetic approach and a simple first-order reaction scheme. The results show that CNTs follow the redox reaction assumption in a simple chemical system. As a result, the reaction with multiwalled CNTs is semi-quantitatively denoted as redox potential, which suggests that their biological reactions may also be evaluated using a redox potential scheme.

Differentiation of chemical reaction activity of various carbon nanotubes using redox potential: Classification by physical and chemical structures.

The present study systematically examined the kinetics of a hydroxyl radical scavenging reaction of various carbon nanotubes (CNTs) including double-walled and multi-walled carbon nanotubes (DWCNTs and MWCNTs), and carbon nano peapods (AuCl3@DWCNT). The theoretical model that we recently proposed based on the redox potential of CNTs was used to analyze the experimental results. The reaction kinetics for DWCNTs and thin MWCNTs agreed well with the theoretical model and was consistent with each other. On the other hand, thin and thick MWCNTs behaved differently, which was consistent with the theory. Additionally, surface morphology of CNTs substantially influenced the reaction kinetics, while the doped particles in the center hollow parts of CNTs (AuCl3@DWCNT) shifted the redox potential in a different direction. These findings make it possible to predict the chemical and biological reactivity of CNTs based on the structural and chemical nature and their influence on the redox potential.

A barley Hordoindoline mutation resulted in an increase in grain hardness.

Barley seed proteins, Hordoindolines, are homologues of wheat Puroindolines, which are associated with grain hardness. Barley Hordoindoline genes are known to comprise Hina and Hinb, and Hinb consists of two Hinb genes, Hinb-1 and Hinb-2. Two types of allele were found for Hina, Hinb-1 and Hinb-2 genes, respectively, among Japanese two- and six-rowed barley lines. One of the alleles of Hinb-2 (Hinb-2b) had a frame-shift mutation resulting in an in-frame stop codon. For two-rowed barley lines, grain hardness was significantly higher among lines with the Hinb-2b than those with the wild type Hinb-2 gene (Hinb-2a). Protein spots corresponding to HINa, HINb-1, and HINb-2 were identified by 2D-gel electrophoresis among barley lines with Hinb-2a. Among the lines with Hinb-2b, HINa and HINb-1 were expressed at similar levels as those in the wild type, but HINb-2 was not detected. A DNA (cleaved amplified polymorphic sequence) marker was developed to distinguish between the Hinb-2a and Hinb-2b gene sequences. Analysis of grain hardness among F(2) lines derived from a cross between a line with Hinb-2a (Shikoku hadaka 115) and a line with the Hinb-2b (Shikoku hadaka 84) showed significantly higher grain hardness in the mutant lines. From these results, the Hinb-2b frame-shift (null) mutation might play a critical role in barley grain hardness. The DNA marker will be useful in barley breeding to select lines having harder grain texture.

Characterization of beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) in a patient with septicemia during long-term vancomycin administration.

It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of beta-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 microg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail.

Inverse iron isotope effect on the transition temperature of the (Ba,K)Fe2As2 superconductor.

We report that the (Ba,K)Fe(2)As(2) superconductor (transition temperature, T(c) approximately 38 K) has an inverse iron isotope coefficient alpha(Fe) = -0.18(3) (where T(c) approximately M(-alphaFe) and M is the iron isotope mass); i.e., the sample containing the large iron isotope mass depicts a higher T(c). Systematic inverse shifts in T(c) were clearly observed between the samples using three types of Fe isotopes ((54)Fe, natural Fe, and (57)Fe). This indicates the first evidence of the inverse isotope effect in high-T(c) superconductors. This anomalous mass dependence on T(c) implies an exotic coupling mechanism in Fe-based superconductors.

Changes in anthocyanins in the grains of purple waxy hull-less barley during seed maturation and after harvest.

Purple waxy hull-less barley cv. Daishimochi accumulates purple pigments in the stem, awn, lemma, palea, and pericarp during seed maturation. Four major anthocyanin constituents from the grains of cv. Daishimochi were isolated and identified as cyanidin 3-O-(3,6-di-O-malonyl-beta-D-glucopyranoside) (55%), cyanidin 3-O-(6-O-malonyl-beta-D-glucopyranoside) (21%), cyanidin 3-O-(3-O-malonyl-beta-D-glucopyranoside) (12%), and cyanidin 3-O-beta- d-glucopyranoside (4%) by mass spectrometry and one- and two-dimensional NMR spectroscopy. These anthocyanins were observed after 28 days after flowering (DAF); they were most abundant at 35 DAF when the dry weight of grains was maximum. This accumulation time was later than that of proanthocyanidins, which are the most abundant polyphenol constituents in barley grains. These anthocyanins, especially cyanidin 3-O-(3,6-di-O-malonyl-beta- d-glucopyranoside), decreased at 42 DAF and during drying preparation after harvest. Most anthocyanins are localized in the outer parts of grains and distributed into bran by the pearling process. Whole grain flour and bran of cv. Daishimochi are good sources of malonylated cyanidin derivatives.