Clinical Usefulness of the Active Fixation Quadripolar Left Ventricular Lead Compared With the Passive Fixation Quadripolar Lead in Cardiac Resynchronization Therapy.

BACKGROUND: This study compared the stability of the Medtronic Attain Stability Quad (ASQ), a novel quadripolar active fixation left ventricular (LV) lead with a side helix, to that of conventional quadripolar leads with passive fixation (non-ASQ) and evaluated their LV lead performance. METHODS AND RESULTS: In all, 183 consecutive patients (69 ASQ, 114 non-ASQ) who underwent cardiac resynchronization therapy (CRT) between January 2018 and June 2021 were enrolled. Complications, including elevated pacing capture threshold (PCT) levels, phrenic nerve stimulation (PNS), and LV lead dislodgement, were analyzed during the postimplantation period until the first outpatient visit after discharge. The frequency of LV lead-related complications was significantly lower in the ASQ than non-ASQ group (14% vs. 30%, respectively; P=0.019). Specifically, LV lead dislodgement occurred only in the non-ASQ group, and elevated PCT levels were significantly lower in the ASQ group (7% vs. 23%; P=0.007). Kaplan-Meier analysis confirmed a significantly lower incidence of LV lead-related complications in the ASQ group (log-rank P=0.005). Cox multivariable regression analysis showed a significant reduction in lead-related complications associated with ASQ (hazard ratio 0.44; 95% confidence interval 0.23-0.83; P=0.011). CONCLUSIONS: The ASQ group exhibited fewer LV lead-related complications requiring reintervention and setting changes than the non-ASQ group. Thus, the ASQ may be a favorable choice for CRT device implantation.

Rice transcription factor DPF regulates stress-induced biosynthesis of diterpenoid phytoalexins.

Diterpenoid Phytoalexin Factor (DPF) is a key transcription factor involved in diterpenoid phytoalexin (DP) biosynthesis under non-stressed conditions in rice (Oryza sativa L.). Using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9, DPF knockout rice lines were generated. Treatments with abiotic stresses (copper chloride, ultraviolet light, and jasmonic acid) and biotic stress (blast fungus infection) to the knockout lines revealed that the DPF positively regulates stress-induced DP biosynthesis.

Genome Editing Reveals Both the Crucial Role of OsCOI2 in Jasmonate Signaling and the Functional Diversity of COI1 Homologs in Rice.

Jasmonic acid (JA) regulates plant growth, development and stress responses. Coronatine insensitive 1 (COI1) and jasmonate zinc-finger inflorescence meristem-domain (JAZ) proteins form a receptor complex for jasmonoyl-l-isoleucine, a biologically active form of JA. Three COIs (OsCOI1a, OsCOI1b and OsCOI2) are encoded in the rice genome. In the present study, we generated mutants for each rice COI gene using genome editing to reveal the physiological functions of the three rice COIs. The oscoi2 mutants, but not the oscoi1a and oscoi1b mutants, exhibited severely low fertility, indicating the crucial role of OsCOI2 in rice fertility. Transcriptomic analysis revealed that the transcriptional changes after methyl jasmonate (MeJA) treatment were moderate in the leaves of oscoi2 mutants compared to those in the wild type or oscoi1a and oscoi1b mutants. MeJA-induced chlorophyll degradation and accumulation of antimicrobial secondary metabolites were suppressed in oscoi2 mutants. These results indicate that OsCOI2 plays a central role in JA response in rice leaves. In contrast, the assessment of growth inhibition upon exogenous application of JA to seedlings of each mutant revealed that rice COIs are redundantly involved in shoot growth, whereas OsCOI2 plays a primary role in root growth. In addition, a co-immunoprecipitation assay showed that OsJAZ2 and OsJAZ5 containing divergent Jas motifs physically interacted only with OsCOI2, whereas OsJAZ4 with a canonical Jas motif interacts with all three rice COIs. The present study demonstrated the functional diversity of rice COIs, thereby providing clues to the mechanisms regulating the various physiological functions of JA.

Structural characteristics of patients with superior vena cava foci initiating atrial fibrillation: Analysis with electrocardiogram-triggered computed tomography.

INTRODUCTION: The superior vena cava (SVC) is the most common source of non-pulmonary vein foci in atrial fibrillation (AF); therefore, predicting the existence of non-pulmonary vein foci before the catheter ablation procedure helps construct a proper ablation strategy in preparation for SVC isolation. This study aimed to clarify the structural characteristics of patients with SVC foci initiating AF. METHODS: We enrolled 331 consecutive patients with AF who underwent cardiac computed tomography imaging before radiofrequency catheter ablation treatment, and they were divided into SVC (+) and (-) groups based on the presence or absence of SVC foci initiating AF. RESULTS: The SVC (+) group (n = 27) exhibited SVC crescent signs-defined as a curve-shaped SVC with two narrow pointed ends-more frequently (37% vs. 9%, p < .001), and larger right atrial volume (95.6 ± 20.8 vs. 80.5 ± 26.1 mL, p = .004) than the SVC (-) group (n = 304). Multivariate logistic regression analysis revealed that the SVC crescent sign (odds ratio, 8.88; 95% confidence interval [CI], 3.21-24.60) and right atrial volume (odds ratio, 1.03; 95% CI, 1.01-1.04) were independent predictors of SVC foci. CONCLUSION: Patients with SVC foci exhibited more frequent SVC crescent signs and larger right atrial volumes, and these characteristics may help clinicians choose the appropriate ablation technology.

Clinical Significance of Atrial Tachyarrhythmia Duration for Ventricular Arrhythmia in Patients With Cardiac Resynchronization Therapy.

BACKGROUND: Atrial tachyarrhythmias (ATAs) are reportedly associated with ventricular arrhythmias (VAs). However, little is known about the association between ATA duration and the risk of VA. We investigated the relationship between ATA duration and subsequent VA in patients with a cardiac resynchronization therapy defibrillator (CRT-D).Methods and Results: We investigated associations between the longest ATA duration during the first year after cardiac resynchronization therapy (CRT) implantation and VA and VA relevant to ATA (VAATA) in 160 CRT-D patients. ATAs occurred in 63 patients in the first year. During a median follow-up of 925 days from 1 year after CRT implantation, 40 patients experienced 483 VAs. Kaplan-Meier analysis showed a significantly higher risk of VA in patients with than without ATA in the first year (log rank P=0.0057). Hazard ratios (HR) of VA (HR 2.36, 2.10, and 3.04 for ATA >30s, >6 min and >24 h, respectively) and only VAATA (HR 4.50, 5.59, and 11.79 for ATA >30s, >6 min and >24 h, respectively) increased according to the duration of ATA. In multivariate analysis, ATA >24 h was an independent predictor of subsequent VA (HR 2.42; P=0.02). CONCLUSIONS: Patients with ATA >24 h in the first year after CRT had a higher risk of subsequent VA and VAATA. The risk of VA, including VAATA, increased with the longest ATA duration.

Transvenous lead extraction versus surgical lead extraction or conservative treatment for cardiac implantable electronic device infections: Propensity score-weighted analyses of a nationwide claim-based database.

INTRODUCTION: Infection is one of the most important complications associated with cardiac implantable electronic device (CIED) therapy. The number of reports comparing the outcomes of transvenous lead extraction (TLE), surgical lead extraction, and conservative treatment for CIED infections using a real-world database is limited. This study investigated the association between the treatment strategies for CIED infections and their outcomes. METHODS: We performed a retrospective analysis of 3605 patients with CIED infections admitted to 681 hospitals using a nationwide claim-based database collected between April 2012 and March 2018. RESULTS: We divided the 3605 patients into TLE (n = 938 [26%]), surgical lead extraction (n = 182 [5.0%]), and conservative treatment (n = 2485 [69%]) groups. TLE was performed more frequently in younger patients and at larger hospitals (p for trend < .001 for both). The rate of TLE increased during the study period, whereas that of surgical lead extraction decreased (p for trend < .001 for both). TLE was associated with lower in-hospital mortality (vs. surgical lead extraction: odds ratio [OR], 0.20; 95% CI, 0.06-0.70; vs. conservative treatment: OR, 0.45; 95% CI: 0.22-0.94) and lower 30-day readmission rates (vs. surgical lead extraction: OR, 0.18; 95% CI: 0.06-0.56; vs. conservative treatment: OR, 0.06; 95% CI, 0.03-0.13) in propensity score-weighted analyses. CONCLUSIONS: Only 26% of patients hospitalized for CIED infections received TLE. TLE was associated with significantly lower in-hospital mortality and 30-day recurrence rates than surgical lead extraction and conservative treatment, suggesting that TLE should be more widely recommended as a first-line treatment for CIED infections.

Chemical and genetic carotenoid deficiency delays growth in dark-grown Euglena gracilis.

Light-independent functions of carotenoids in photosynthetic organisms are poorly understood. Here, we investigated the growth properties of microalga, Euglena gracilis, under altered light and temperature using norflurazon-treated carotenoid-deficient cells and genetically modified strains, including nonphotosynthetic SM-ZK and colorless cl4. Norflurazon treatment decreased carotenoid and chlorophyll contents, causing cell bleaching. SM-ZK strain had lower carotenoid content than wild-type (WT) strain, and it was below the detectable level in the cl4 strain. Norflurazon treatment decreased phytoene synthase EgCrtB levels, although EgcrtB was transcriptionally induced. Carotenoid deficiency in norflurazon-treated cells and the cl4 strain caused similar extents of delayed growth under light and dark conditions at 25 °C, indicating that carotenoids promote growth in darkness. Both WT and SM-ZK strains exhibited similar growth rates. Dark conditions at 20 °C enhanced the growth delay of norflurazon-treated cells and the cl4 strain. These results indicate that carotenoids impart environmental stress tolerance to E. gracilis in light-dependent and light-independent manners.

Difference in the ligand affinity among redundant plant hormone receptors of rice OsCOI1a/1b/2-OsJAZs.

(3R, 7S)-jasmonoyl-L-isoleucine (JA-Ile) is a lipid-derived plant hormone that regulates plant responses, including biotic/abiotic stress adaptation. In the plant cells, JA-Ile is perceived by COI1-JAZ co-receptor by causing protein-protein interaction between COI1 and JAZ proteins to trigger gene expressions. In this study, we focused on Oryza sativa, a model monocot and an important crop, with 45 possible OsCOI-OsJAZ co-receptor pairs composed of three OsCOI homologs (OsCOI1a, OsCOI1b, and OsCOI2) and 15 OsJAZ homologs. We performed fluorescein anisotropy and pull-down assays to examine the affinity between JA-Ile and OsCOI1a/1b/2-OsJAZ1-15 co-receptor pairs. The results revealed a remarkable difference in the modes of ligand perception by OsCOI1a/1b and OsCOI2. Recently, the unique function of OsCOI2 in some of the JA-responses were revealed. Our current results will lead to the possible development of OsCOI2-selective synthetic ligand.

Characterization of diterpene synthase genes in Brachypodium distachyon, a monocotyledonous model plant, provides evolutionary insight into their multiple homologs in cereals.

Gibberellins are diterpenoid phytohormones that regulate plant growth, and are biosynthesized from a diterpene intermediate, ent-kaurene, which is produced from geranylgeranyl diphosphate via ent-copalyl diphosphate (ent-CDP). The successive 2 cyclization reactions are catalyzed by 2 distinct diterpene synthases, ent-CDP synthase (ent-CPS) and ent-kaurene synthase (KS). Various diterpene synthase genes involved in specialized metabolism were likely created through duplication and neofunctionalization of gibberellin-biosynthetic ent-CPS and KS genes in crops. Brachypodium distachyon is a monocotyledonous species that is a model plant in grasses. We herein found 1 ent-CPS gene homolog BdCPS and 4 tandemly arrayed KS-like genes BdKS1, KSL2, KSL3, and KSL4 in the B. distachyon genome, a simpler collection of paralogs than in crops. Phylogenetic and biochemical analyses showed that BdCPS and BdKS1 are responsible for gibberellin biosynthesis. BdKSL2 and BdKSL3 are suggested to be involved in specialized diterpenoid metabolism. Moreover, we restored KS activity of BdKSL2 through amino acid substitution.

Genomic evidence for convergent evolution of gene clusters for momilactone biosynthesis in land plants.

Momilactones are bioactive diterpenoids that contribute to plant defense against pathogens and allelopathic interactions between plants. Both cultivated and wild grass species of Oryza and Echinochloa crus-galli (barnyard grass) produce momilactones using a biosynthetic gene cluster (BGC) in their genomes. The bryophyte Calohypnum plumiforme (formerly Hypnum plumaeforme) also produces momilactones, and the bifunctional diterpene cyclase gene CpDTC1/HpDTC1, which is responsible for the production of the diterpene framework, has been characterized. To understand the molecular architecture of the momilactone biosynthetic genes in the moss genome and their evolutionary relationships with other momilactone-producing plants, we sequenced and annotated the C. plumiforme genome. The data revealed a 150-kb genomic region that contains two cytochrome P450 genes, the CpDTC1/HpDTC1 gene and the "dehydrogenase momilactone A synthase" gene tandemly arranged and inductively transcribed following stress exposure. The predicted enzymatic functions in yeast and recombinant assay and the successful pathway reconstitution in Nicotiana benthamiana suggest that it is a functional BGC responsible for momilactone production. Furthermore, in a survey of genomic sequences of a broad range of plant species, we found that momilactone BGC is limited to the two grasses (Oryza and Echinochloa) and C. plumiforme, with no synteny among these genomes. These results indicate that while the gene cluster in C. plumiforme is functionally similar to that in rice and barnyard grass, it is likely a product of convergent evolution. To the best of our knowledge, this report of a BGC for a specialized plant defense metabolite in bryophytes is unique.

Sphingadienine-1-phosphate levels are regulated by a novel glycoside hydrolase family 1 glucocerebrosidase widely distributed in seed plants.

Long-chain base phosphates (LCBPs) such as sphingosine-1-phosphate and phytosphingosine-1-phosphate function as abscisic acid (ABA)-mediated signaling molecules that regulate stomatal closure in plants. Recently, a glycoside hydrolase family 1 (GH1) ß-glucosidase, Os3BGlu6, was found to improve drought tolerance by stomatal closure in rice, but the biochemical functions of Os3BGlu6 have remained unclear. Here we identified Os3BGlu6 as a novel GH1 glucocerebrosidase (GCase) that catalyzes the hydrolysis of glucosylceramide to ceramide. Phylogenetic and enzymatic analyses showed that GH1 GCases are widely distributed in seed plants and that pollen or anthers of all seed plants tested had high GCase activity, but activity was very low in ferns and mosses. Os3BGlu6 had high activity for glucosylceramides containing (4E,8Z)-sphingadienine, and GCase activity in leaves, stems, roots, pistils, and anthers of Os3BGlu6-deficient rice mutants was completely absent relative to that of wild-type rice. The levels of ceramides containing sphingadienine were correlated with GCase activity in each rice organ and were significantly lower in Os3BGlu6-deficient rice mutants than in the wild type. The levels of LCBPs synthesized from ceramides, especially the levels of sphingadienine-1-phosphate, were also correlated with GCase activity in each rice organ and were significantly lower in Os3BGlu6-deficient rice mutants than in the wild type. These results indicate that Os3BGlu6 regulates the level of ceramides containing sphingadienine, influencing the regulation of sphingadienine-1-phosphate levels and subsequent improvement of drought tolerance via stomatal closure in rice.

Chitooligosaccharide elicitor and oxylipins synergistically elevate phytoalexin production in rice.

KEY MESSAGE: We show that in rice, the amino acid-conjugates of JA precursor, OPDA, may function as a non-canonical signal for the production of phytoalexins in coordination with the innate chitin signaling. The core oxylipins, jasmonic acid (JA) and JA-Ile, are well-known as potent regulators of plant defense against necrotrophic pathogens and/or herbivores. However, recent studies also suggest that other oxylipins, including 12-oxo-phytodienoic acid (OPDA), may contribute to plant defense. Here, we used a previously characterized metabolic defense marker, p-coumaroylputrescine (CoP), and fungal elicitor, chitooligosaccharide, to specifically test defense role of various oxylipins in rice (Oryza sativa). While fungal elicitor triggered a rapid production of JA, JA-Ile, and their precursor OPDA, rice cells exogenously treated with the compounds revealed that OPDA, rather than JA-Ile, can stimulate the CoP production. Next, reverse genetic approach and oxylipin-deficient rice mutant (hebiba) were used to uncouple oxylipins from other elicitor-triggered signals. It appeared that, without oxylipins, residual elicitor signaling had only a minimal effect but, in synergy with OPDA, exerted a strong stimulatory activity towards CoP production. Furthermore, as CoP levels were compromised in the OPDA-treated Osjar1 mutant cells impaired in the oxylipin-amino acid conjugation, putative OPDA-amino acid conjugates emerged as hypothetical regulators of CoP biosynthesis. Accordingly, we found several OPDA-amino acid conjugates in rice cells treated with exogenous OPDA, and OPDA-Asp was detected, although in small amounts, in the chitooligosaccharide-treated rice. However, as synthetic OPDA-Asp and OPDA-Ile, so far, failed to induce CoP in cells, it suggests that yet another presumed OPDA-amino acid form(s) could be acting as novel regulator(s) of phytoalexins in rice.

The rice wound-inducible transcription factor RERJ1 sharing same signal transduction pathway with OsMYC2 is necessary for defense response to herbivory and bacterial blight.

KEY MESSAGE: This study describes biological functions of the bHLH transcription factor RERJ1 involved in the jasmonate response and the related defense-associated metabolic pathways in rice, with particular focus on deciphering the regulatory mechanisms underlying stress-induced volatile emission and herbivory resistance. RERJ1 is rapidly and drastically induced by wounding and jasmonate treatment but its biological function remains unknown as yet. Here we provide evidence of the biological function of RERJ1 in plant defense, specifically in response to herbivory and pathogen attack, and offer insights into the RERJ1-mediated regulation of metabolic pathways of specialized defense compounds, such as monoterpene linalool, in possible collaboration with OsMYC2-a well-known master regulator in jasmonate signaling. In rice (Oryza sativa L.), the basic helix-loop-helix (bHLH) family transcription factor RERJ1 is induced under environmental stresses, such as wounding and drought, which are closely linked to jasmonate (JA) accumulation. Here, we investigated the biological function of RERJ1 in response to biotic stresses, such as herbivory and pathogen infection, using an RERJ1-defective mutant. Transcriptome analysis of the rerj1-Tos17 mutant revealed that RERJ1 regulated the expression of a typical family of conserved JA-responsive genes (e.g., terpene synthases, proteinase inhibitors, and jasmonate ZIM domain proteins). Upon exposure to armyworm attack, the rerj1-Tos17 mutant exhibited more severe damage than the wildtype, and significant weight gain of the larvae fed on the mutant was observed. Upon Xanthomonas oryzae infection, the rerj1-Tos17 mutant developed more severe symptoms than the wildtype. Among RERJ1-regulated terpene synthases, linalool synthase expression was markedly disrupted and linalool emission after wounding was significantly decreased in the rerj1-Tos17 mutant. RERJ1 appears to interact with OsMYC2-a master regulator of JA signaling-and many OsJAZ proteins, although no obvious epistatic interaction was detected between them at the transcriptional level. These results indicate that RERJ1 is involved in the transcriptional induction of JA-mediated stress-responsive genes via physical association with OsMYC2 and mediates defense against herbivory and bacterial infection through JA signaling.

Zero-fluoroscopy ablation in patients with cardiac electronic implantable devices.

INTRODUCTION: Utilizing a three-dimensional (3-D) mapping system and intracardiac echocardiography (ICE) has allowed ablation procedures with less or without fluoroscopy; however, there is limited data for patients with cardiac electronic implantable device (CIED) leads regarding the suspected risk of lead injury. Therefore, we sought to explore technics to perform safe trans-septal approach and catheter manipulation technique in patients with CIED leads. METHODS AND RESULTS: This study comprised 49 consecutive patients (59% males, median 73 years old) with CIED who underwent catheter ablation for supraventricular tachycardia requiring the trans-septal approach, 15 without fluoroscopy (zero-fluoro group), and 34 with fluoroscopy (conventional-fluoro group), between July 2019 and April 2021. All procedures were performed under a 3-D mapping system and ICE guidance. We compared the differences in treatment and development of complications between the two groups. The procedures were for atrial fibrillation (82%) and atrial tachycardia (76%). Coronary sinus catheter insertion and the trans-septal procedure were successfully performed in all patients. The median time from venipuncture to trans-septal procedure (zero-fluoro vs. conventional-fluoro group: 28 [18-37] min vs. 24 [21-31] min, p = .70), total procedure time (231 [142-274] min vs. 175 [163-225] min, p = .63), and the acute procedural success rate (100% vs. 97%, p = 1.00) did not differ between both groups. No patient showed lead-related complications in both groups. CONCLUSION: This is the first study to show zero-fluoro ablation for supraventricular arrhythmia using 3-D mapping and ICE in patients with CIED leads was feasible under careful catheter manipulation.

Impact of nocturnal hypoxemia on the recurrence of atrial tachyarrhythmia after catheter ablation of atrial fibrillation.

Factors causing atrial tachyarrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF) remain undetermined. This study aimed to investigate the effect of nocturnal hypoxemia on the recurrence of atrial tachyarrhythmia after CA of AF. Among 594 patients with AF who underwent an ambulatory sleep study at the National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (2014-2019), 365 underwent CA of AF; 290 patients who underwent CA were followed up for > 3 months. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) using clinical variables, to identify the independent predictors of atrial tachyarrhythmia recurrence after the final CA. Atrial tachyarrhythmia recurred in 45 of 290 (15.5%) patients during the median follow-up period of 479 days (interquartile range 225-1002). On the performing multivariate analysis of the data of patients who did not receive continuous positive airway pressure (CPAP), severe nocturnal hypoxemia [defined as the percentage of sleep time spent with SaO2 of < 90% (T90) over 20%] [HR 8.53, 95% confidence interval (CI) 1.872-38.814; P < 0.01] and an 1 mL/m2 increase in the left atrial volume index (HR 1.02, 95% CI 1.004-1.044; P = 0.02) were found to be independently associated with the recurrence of atrial tachyarrhythmia. In addition, the rates of freedom from atrial tachyarrhythmia after the final AF ablation with CPAP were significantly lower in the group with more severe nocturnal hypoxemia (Log-rank P = 0.03). In conclusion, it is necessary to consider both, AHI and nocturnal hypoxia while performing an ambulatory sleep apnea study. CA may be less effective in patients with more severe nocturnal hypoxia, despite the administration of CPAP.

Impact of Pre-Ablation Direct Current Cardioversion for Persistent Atrial Fibrillation to Predict Recurrence of Atrial Fibrillation after Catheter Ablation.

The efficacy of direct current (DC) cardioversion before catheter ablation (CA) for persistent atrial fibrillation (PerAF) patients remains controversial. We hypothesized that maintenance of sinus rhythm (SR) by pre-ablation DC cardioversion may predict the outcome of CA in patients with PerAF. A total of 383 PerAF patients with no or mild symptoms (EHRA I/II) who had undergone DC cardioversion before CA (301 males, 65 ± 10 years old, mean atrial fibrillation (AF) duration: 25 ± 47 months) were retrospectively enrolled. Whether or not SR was maintained at least 24 hour after DC cardioversion, patients were divided into two groups, namely, the DC-SR group and DC-AF group, and then all were followed until AF recurrence after CA. After DC cardioversion, 281 (73%) patients were categorized into the DC-SR group, and 102 (27%) were categorized into the DC-AF group. A total of 195 patients underwent CA at an average of 83 (54-145) days after DC cardioversion, including 161 (83%) in the DC-SR group and 34 (17%) in the DC-AF group. During follow-up (median: 15 [10-25] months), the number of patients who were free from AF was significantly higher in the DC-SR group compared with the DC-AF group (61.5% versus 38.3%, P < 0.0001). Multivariate analysis revealed that the DC-SR group (hazard ratio [HR]: 0.45, 95% confidence interval [CI]: 0.21-0.99, P = 0.047) and age at first AF diagnosis (HR: 0.95, 95% CI: 0.91-1.00, P = 0.039) were the independent predictors for being AF-free after CA. In conclusion, the 24-hour rhythm outcome of pre-ablation DC cardioversion and age at first AF diagnosis may predict the recurrence of AF after CA in patients with PerAF.

An anatomical approach to determine the location of the sinoatrial node during catheter ablation.

INTRODUCTION: The sinoatrial node (SAN) should be identified before superior vena cava (SVC) isolation to avoid SAN injury. However, its location cannot be identified without restoring sinus rhythm. This study evaluated the usefulness of the anatomically defined SAN by comparing it with the electrically confirmed SAN (e-SAN) to predict the top-most position of e-SAN and thus establish a safe and more efficient anatomical reference for SVC isolation than the previously reported reference of the right superior pulmonary vein (RSPV) roof. METHODS AND RESULTS: The e-SAN was identified as the earliest activation site in the electroanatomical map obtained during sinus rhythm. The anatomically defined SAN, the cranial edge of the crista terminalis (CT) visualized with intracardiac echocardiography (CT top), and the RSPV roof, which was obtained from the overlaid electroanatomical image of SVC and RSPV, were tagged on one map. The distance from the e-SAN to each reference was measured. Among 77 patients, the height of the e-SAN from the CT top was a median (interquartile range) of -2.0 (-8.0 to 4.0) mm. The e-SAN existed from 10 mm above the CT top or lower in 74 (96%) patients and from the RSPV roof or below in 73 (95%) patients. The reference of 10 mm above the CT top is more proximal to the right atrium than the RSPV roof and can provide longer isolatable SVC sleeves (30.0 [20.0-35.0] vs. 24.0 [18.0-30.0] mm, p < .001). The e-SAN tended to be found above the CT top when the heart rate during mapping was faster (adjusted odds ratio [95% confidence interval] per 10-bpm increase: 1.71 [1.20-2.43], p < .01). CONCLUSION: The CT top is useful for predicting the upper limit of the e-SAN and can provide a better reference for SVC isolation than the RSPV roof.

High-risk atrioventricular block in Brugada syndrome patients with a history of syncope.

BACKGROUND: Determining the etiology of syncope is challenging in Brugada syndrome (BrS) patients. Implantable cardioverter defibrillator placement is recommended in BrS patients who are presumed to have arrhythmic syncope. However, arrhythmic syncope in BrS patients can occur in the setting of atrioventricular block (AVB), which should be managed by cardiac pacing. The clinical characteristics of BrS patients with high-risk AVB remain unknown. METHODS: This study included 223 BrS patients with a history of syncope from two centers. The clinical characteristics of patients with high-risk AVB (Mobitz type II second-degree AVB, high-degree AVB, or third-degree AVB) were investigated. RESULTS: During the 99 ± 78 months of follow-up, we identified six BrS patients (2.7%) with high-risk AVB. Three of the six patients (50%) with AVB presented with syncope associated with prodromes or specific triggers. Four patients (67%) were found to have paroxysmal third-degree AVB during the initial evaluation for BrS and syncope, while two patients developed third-degree AVB during the follow-up period. The incidence of first-degree AVB was significantly higher in AVB patients than in non-AVB patients (83% vs. 15%; p = .0005). There was no significant difference in the incidence of ventricular fibrillation between AVB and non-AVB patients (AVB [17%], non-AVB [12%]; p = .56). CONCLUSION: High-risk AVB can occur in BrS patients with various clinical presentations. Although rare, the incidence is worth considering, especially in BrS patients with first-degree AVB.

Observation of Spin-Momentum-Layer Locking in a Centrosymmetric Crystal.

The spin polarization in nonmagnetic materials is conventionally attributed to the outcome of spin-orbit coupling when the global inversion symmetry is broken. The recently discovered hidden spin polarization indicates that a specific atomic site asymmetry could also induce measurable spin polarization, leading to a paradigm shift in research on centrosymmetric crystals for potential spintronic applications. Here, combining spin- and angle-resolved photoemission spectroscopy and theoretical calculations, we report distinct spin-momentum-layer locking phenomena in a centrosymmetric, layered material, BiOI. The measured spin is highly polarized along the Brillouin zone boundary, while the same effect almost vanishes around the zone center due to its nonsymmorphic crystal structure. Our work demonstrates the existence of momentum-dependent hidden spin polarization and uncovers the microscopic mechanism of spin, momentum, and layer locking to each other, thus shedding light on the design metrics for future spintronic materials.

Effectiveness and Safety of Rivaroxaban by General Practitioners　- A Multicenter, Prospective Study in Japanese Patients With Non-Valvular Atrial Fibrillation (GENERAL).

BACKGROUND: Direct oral anticoagulants have become a standard therapy for non-valvular atrial fibrillation (NVAF). However, little is known about their effectiveness/safety when prescribed by general practitioners to treat high-risk populations such as the elderly, those who are frail or have cognitive dysfunction.Methods and Results:In this multicenter, prospective study, a total of 5,717 NVAF patients (mean age 73.9 years) receiving rivaroxaban were registered by general practitioners, with a maximum 3-year follow up (mean 2.0±0.5 years). The primary endpoint was a composite of stroke and systemic embolism (SE). The annual incidence (per 100 person-years) of stroke/SE was 1.23% and for major bleeding, it was 0.63%. Multivariate analyses identified age ≥75 years (hazard ratio [HR]; 2.67, P<0.001) and history of ischemic stroke (HR; 1.89, P=0.005) as significant risk factors of stroke/SE, with history of major bleeding (HR; 14.9, P<0.001) and warfarin use (HR; 2.15, P=0.002) as risk factors for major bleeding events. Neither cognitive dysfunction, defined by the receipt of anti-dementia medications, nor frailty, evaluated by the classification of the Japanese Long-term Care Insurance system, correlated with stroke/SE or major bleeding events. CONCLUSIONS: The low incidence of adverse events, including stroke/SE and bleeding, in patients prescribed rivaroxaban by general practitioners supports its use as a safe and efficacious treatment in the standard clinical care of high-risk patient populations.