Left atrial low voltage areas and heart failure in patients with atrial fibrillation: Implication of the atrial myopathy.

AIMS: Atrial fibrillation (AF) and heart failure (HF) affect each other and are often co-morbid. The fact that HF development is not uncommon even after ablation suggests that we need a deeper understanding of the pathology of these conditions. Atrial myocardial degeneration is an underlying factor in AF patients and may be associated with HF development after ablation. This study aimed to investigate the impact of low-voltage areas (LVAs) on HF prognosis after AF ablation. METHODS AND RESULTS: This observational study included 1481 consecutive patients undergoing initial ablation for AF. Left atrial LVAs were defined as regions with a bipolar peak-to-peak voltage of <0.50 mV. Patients were divided into three groups: no LVA (LVA size indexed to body surface area <3 cm2/m2, n = 1129), small LVA (3-10 cm2/m2, n = 217), and extensive LVA (≥10 cm2/m2, n = 135). A composite endpoint of HF hospitalization or death occurred more frequently in patients with larger LVAs (3.3% vs. 6.5% vs. 13.3%, P < 0.0001) during the 3-year follow up period. The extent of LVAs was independently related to the risk of the composite endpoint with an adjusted hazard ratio of 1.55 (95% confidence interval, 1.16-2.10) for each additional step of LVA classification (P = 0.003). CONCLUSIONS: LVA presence and its extent were associated with frequent HF hospitalization and death. Underlying atrial myopathy appears to define a poor HF prognosis after AF ablation.

Extensive ablation for persistent atrial fibrillation patients with mitral regurgitation: Insights from the EARNEST-PVI prospective randomized trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients. METHODS: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications. RESULTS: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54-1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22-0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms. CONCLUSIONS: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management.

Impact of Immunosuppressive Therapy on Lead Dislodgement After Cardiac Implantable Electronic Device Implantation.

BACKGROUNDS: Lead dislodgement is a severe complication in cardiac implantable electronic device (CIED) implantation. Inflammation after CIED implantation results in the development of adhesions between lead and tissues, resulting in the lead becoming fixed in the body. In patients with immunosuppressive therapy, however, adhesion is inhibited by anti-inflammatory effects. However, the association between lead dislodgement and immunosuppressive therapy has not been clarified. The purpose of this study was to investigate the association between lead dislodgement and immunosuppressive therapy. HYPOTHESIS: We hypothesized that lead dislodgement more frequently occur in patients with immunosuppressive therapy than those without. METHODS: In total, 651 consecutive patients who underwent CIED implantation or lead addition (age, 76 ± 11 years; and males, 374 [58%], high voltage device, 121 [19%], lead addition 23 [4%]) were retrospectively enrolled. Immunosuppressive therapy was with regular steroids or immunosuppressants. Lead placement was guided by fluoroscopy, and active fixation leads were used. Restraint of the upper limb by chest tape was performed for 1 week after the procedure. Lead dislodgement was defined as a change in lead position and/or lead failure requiring reoperation. RESULTS: Twenty (3.1%) patients received immunosuppressive therapy. Among these, 15 (2.3%) patients regularly took steroids and 8 (1.2%) took immunosuppressants. Lead dislodgement occurred in 10 (1.5%) patients. Lead dislodgement was more frequent in patients with immunosuppressive therapy than in those without (3 [15%] vs. 7 [1%], p = 0.003). CONCLUSION: In patients with CIED implantation or lead addition, lead dislodgement is more frequent in patients with immunosuppressive therapy than in those without.

Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

BACKGROUND: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers.Methods and Results: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). CONCLUSIONS: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Solvent stabilizing effects on the order-disorder transition of schizophyllan in aqueous mixtures of carboxylic acids.

Schizophyllan is a triple helical ß-1,3-D-glucan, and shows the cooperative order-disorder transition in the aqueous solution at the triple helix state. In this paper, the solvent stabilizing effects of two carboxylic acids, acetic acid and citric acid, on the cooperative order-disorder transition of aqueous schizophyllan solution were investigated from DSC and SEC-MALS measurements. The transition temperature (Tr) was shifted to higher temperature with increasing the molar fraction of carboxylic acid in the mixture (x). The transition enthalpy (ΔHr) was increased with increasing x. These solvent stabilizing effects indicate that these carboxylic acid molecules were selectively associated with the branched side chains of schizophyllan to stabilize the ordered state. The composition dependencies of Tr and ΔHr were analyzed by the linear cooperative transition theory to estimate the association parameters between the side chains and carboxylic acid. The theoretical parameters obtained were compared with those for the other active substances for the transition to discuss the molecular interactions between the triple helix and carboxylic acid.

Impact of wall thickness on the tissue cooling effect of cryoballoon ablation.

AIMS: Understanding of the tissue cooling properties of cryoballoon ablation during pulmonary vein (PV) isolation is lacking. The purpose of this study was to delineate the depth of the tissue cooling effect during cryoballoon freezing at the pulmonary venous ostium. METHODS AND RESULTS: A left atrial-PV model was constructed using a three-dimensional printer with data from a patient to which porcine thigh muscle of various thicknesses could be affixed. The model was placed in a 37°C water tank with a PV water flow at a rate that mimicked biological blood flow. Cryofreezing at the PV ostium was performed five times each for sliced porcine thigh muscle of 2, 4, and 6 mm thickness, and sliced muscle cooling on the side opposite the balloon was monitored. The cooling effect was assessed using the average temperature of 12 evenly distributed thermocouples covering the roof region of the left superior PV. Tissue cooling effects were in the order of the 2, 4, and 6 mm thicknesses, with an average temperature of -41.4 ± 4.2°C for 2 mm, -33.0 ± 4.0°C for 4 mm, and 8.0 ± 8.7°C for 6 mm at 180 s (P for trend <0.0001). In addition, tissue temperature drops were steeper in thin muscle (maximum temperature drop per 5 s: 5.2 ± 0.9°C, 3.9 ± 0.7°C, and 1.3 ± 0.7°C, P for trend <0.0001). CONCLUSION: The cooling effect of cryoballoon freezing is weaker in the deeper layers. Cryoballoon ablation should be performed with consideration to myocardial thickness.

Prostanoids Regulate Angiogenesis and Lymphangiogenesis in Pathological Conditions.

Angiogenesis, the formation of new blood vessels from the preexistent microvasculature, is an essential component of wound repair and tumor growth. Nonsteroidal anti-inflammatory drugs that suppress prostanoid biosynthesis are known to suppress the incidence and progression of malignancies including colorectal cancers, and also to delay the wound healing. However, the precise mechanisms are not fully elucidated. Accumulated results obtained from prostanoid receptor knockout mice indicate that a prostaglandin E-type receptor signaling EP3 in the host microenvironment is critical in tumor angiogenesis inducing vascular endothelial growth factor A (VEGF-A). Further, lymphangiogenesis was also enhanced by EP signaling via VEGF-C/D inductions in pathological settings. These indicate the importance of EP receptor to facilitate angiogenesis and lymphangiogenesis in vivo. Prostanoids act beyond their commonly understood activities in smooth muscle contraction and vasoactivity, both of which are quick responses elicited within several seconds on stimulations. Prostanoid receptor signaling will be a potential therapeutic target for disease conditions related to angiogenesis and lymphangiogenesis.

Atrial Functional Substrates for the Prediction of Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

Low-voltage areas have been used as atrial structural substrates in estimating fibrotic degeneration in patients with atrial fibrillation (AF). The high-resolution maps obtained by recently developed mapping catheters allow the visualization of several functional abnormalities. We investigated the association between left atrial (LA) functional abnormal findings on a high-resolution substrate map and AF recurrence in patients who underwent pulmonary vein isolation without any additional LA substrate ablation. This observational study included 100 consecutive patients who underwent second ablation for AF (paroxysmal, 48%; persistent, 52%). Patients with extra-pulmonary-vein LA substrate ablation during the initial and second ablation were excluded. LA mapping was performed using a 64-pole mini-basket catheter on the RHYTHMIA mapping system (Boston Scientific, Marlborough [Cambridge] Massachusetts). Patients were followed for 2 years. AF recurrence developed in 39 (39%) patients. On the high-resolution substrate map, AF recurrence was associated with the presence of the following findings: low-voltage areas (<1.0 mV, >5 cm2; hazard ratio [HR] = 2.53; 95% confidence interval [CI] = 1.30 to 4.93; p <0.006), fractionated-electrogram areas (≥5 peaks, >5 cm2; HR = 2.15, 95% CI = 1.10 to 4.19; p = 0.025), LA conduction time of >130 ms (HR = 3.11, 95% CI = 1.65 to 5.88, p <0.0001), deceleration zone (≥5 isochrones/cm2; HR = 1.97, 95% CI = 1.04 to 3.37, p = 0.039), and multiple septal break-out points (HR = 3.27, 95% CI = 1.50 to 7.16, p = 0.003). Accumulation of these risk factors increased AF recurrence in a stepwise manner, with an HR = 1.90, 95% CI = 1.44 to 2.52, p <0.00001 for each additional risk factor. In conclusion, a high-resolution map revealed new LA functional substrates associated with AF recurrence. Implementation of functional substrates may improve the prediction of AF recurrence after ablation, and possibly aid the development of tailored AF ablation strategies.

Differential changes in blood flow and oxygen utilization in active muscles between voluntary exercise and electrical muscle stimulation in young adults.

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants.NEW & NOTEWORTHY This is the first study to visualize continuous changes in blood flow and oxygen utilization within contracted muscles during and after electrical muscle stimulation (EMS) using combined diffuse correlation and near-infrared spectroscopy. We found that initiating EMS increases blood flow at a rate comparable to that during voluntary (VOL) exercise but enhances oxygen extraction, resulting in higher oxygen consumption. Furthermore, EMS increased postexercise muscle perfusion and oxygen consumption compared with that after VOL exercise.

Impact of diabetes mellitus and poor glycemic control on the prevalence of left atrial low-voltage areas and rhythm outcome in patients with atrial fibrillation ablation.

INTRODUCTION: Left atrial low-voltage areas (LVAs) are known to be correlated with atrial scarring and atrial fibrillation (AF) recurrence after ablation. However, the association between LVAs and glycemic status before ablation has not been fully clarified. The purpose of this study was to investigate associations among the prevalence of diabetes mellitus (DM), glycemic control, and the prevalence of LVAs in patients with AF ablation. METHODS: In total, 912 (age, 68 ± 10 years; female, 299 [33%]; persistent AF, 513 [56%]) consecutive patients who underwent initial AF ablation were included. A preprocedure glycated hemoglobin A1c (HbA1c) ≥7% was set as the cutoff for poor glycemic control in patients with DM. LVAs were defined as areas with a bipolar voltage of <0.5 mV covering ≥5 cm2 of left atrium. RESULTS: LVAs existed in 208 (23%) patients, and 168 (18%) patients had DM. LVAs were found more frequently in patients with DM and poor glycemic control. On multivariate analysis, DM with HbA1c ≥7% was an independent predictor of LVAs (odds ratio, 3.3; 95% confidence interval: 1.6-6.7; p = .001). In patients with LVAs, freedom from AF recurrence during the 24-month study period was significantly lower in patients who had DM with HbA1c ≥7% than in those without DM (37.9% vs. 54.7%, p = .02). CONCLUSION: In patients with AF ablation, LVAs were found more frequently in patients with DM and poor glycemic control. DM with HbA1c ≥7% was an independent predictor of LVAs.

Uplift modeling to identify patients who require extensive catheter ablation procedures among patients with persistent atrial fibrillation.

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.

Duration of atrial fibrillation persistence: Implications for recurrence risk after catheter ablation and efficacy of additional substrate ablation.

BACKGROUND: The optimal duration of atrial fibrillation (AF) persistence for predicting poor outcomes after catheter ablation of long-standing AF (LsAF) and the best ablation strategy for these patients remain unclear. OBJECTIVE: We aimed to assess the impact of the duration of AF persistence on outcomes after catheter ablation of AF. METHODS: We analyzed the Efficacy of Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation (EARNEST-PVI) trial data comparing pulmonary vein isolation (PVI) alone (PVI-alone) with additional linear ablation or defragmentation (PVI-plus) in persistent AF (PerAF). Patients who received catheter ablation by contact force-sensing catheter were enrolled in the study. In patients with LsAF, the optimal cutoff duration of AF persistence was evaluated. With use of the threshold, patients with LsAF were divided into 2 groups and compared with PerAF <1 year for arrhythmia-free survival after a 3-month blanking period. RESULTS: The optimal cutoff duration was 2.4 years. Of 458 patients, arrhythmia-free survival rates for LsAF 1-2.4 years were comparable to those of PerAF (hazard ratio [HR], 1.01; 95% CI, 0.67-1.52). However, LsAF >2.4 years had a higher recurrence risk than PerAF (HR, 2.22; 95% CI, 1.42-3.47). In LsAF >2.4 years, the PVI-plus strategy showed advantages over the PVI-alone strategy (HR, 0.36; 95% CI, 0.14-0.89). However, the interaction effect between LsAF 1-2.4 years and LsAF >2.4 years did not reach statistical significance (P = .116). CONCLUSION: Whereas LsAF 1-2.4 years has similar outcomes to those of PerAF, LsAF >2.4 years was linked to higher arrhythmia recurrence risks. For LsAF >2.4 years, the PVI-plus strategy showed a potential to be superior to the PVI-alone strategy.

Clinical impact of left atrial remodeling pattern in patients with atrial fibrillation: Comparison of volumetric, electrical, and combined remodeling.

INTRODUCTION: Atrial fibrillation (AF) is accompanied by various types of remodeling, including volumetric enlargement and histological degeneration. Electrical remodeling reportedly reflects histological degeneration. PURPOSE: To clarify the differences in determinants and clinical impacts among types of remodeling. METHODS: This observational study included 1118 consecutive patients undergoing initial ablation for AF. Patients were divided into four groups: minimal remodeling (left atrial volume index [LAVI] < mean value and no low-voltage area [LVA], n = 477); volumetric remodeling (LAVI ≥ mean value and no LVA, n = 361); electrical remodeling (LAVI < mean value and LVA presence, n = 96); and combined remodeling (LAVI ≥ mean value and LVA presence, n = 184). AF recurrence and other clinical outcomes were followed up for 2 and 5 years, respectively. RESULTS: Major determinants of each remodeling pattern were high age for electrical (odds ratio = 2.32, 95% confidence interval = 1.68-3.25) and combined remodeling (2.57, 1.88-3.49); female for electrical (3.85, 2.21-6.71) and combined remodeling (4.92, 2.90-8.25); persistent AF for combined remodeling (7.09, 3.75-13.4); and heart failure for volumetric (1.71, 1.51-2.53) and combined remodeling (2.21, 1.30-3.75). Recurrence rate after initial ablation increased in the order of minimal remodeling (20.1%), volumetric (27.4%) or electrical remodeling (36.5%), and combined remodeling (50.0%, p < .0001). A composite endpoint of heart failure, stroke, and death occurred in the order of minimal (3.4%), volumetric (7.5%) or electrical (8.3%), and combined remodeling (15.2%, p < .0001). CONCLUSION: Volumetric, electrical, and combined remodeling were each associated with a unique patient background, and defined rhythm and other clinical outcomes.

Comparison of voltage maps using OCTARAY catheter and PENTARAY catheter.

BACKGROUND: Recently, a new OCTARAY® mapping catheter was commercially launched. The catheter is designed to enable high-density mapping and precise signal recording via 48 small electrodes arranged on eight radiating splines. The purpose of this study was to compare bipolar voltage and low-voltage-area size, and mapping efficacy between the OCTARAY catheter and the PENTARAY® catheter METHODS: Twelve consecutive patients who underwent initial and second ablations for persistent atrial fibrillation within 2 years were considered for enrollment. Voltage mapping was performed twice, first during the initial ablation using the PENTARY catheter and second during the second ablation using the OCTARAY Long 3-3-3-3-3 (L3) catheter. RESULTS: Mean voltage with the OCTARAY-L3 catheter (1.64 ± 0.57 mV) was 32.3% greater than that with the PENTARAY catheter (1.24 ± 0.46 mV, p < .0001) in total left atrium. Low-voltage-area (<0.50 mV) size with the OCTARAY-L3 catheter was smaller than that with the PENTARAY catheter (6.9 ± 9.7 vs. 11.4 ± 13.0 cm2 , p < .0001). The OCTARAY-L3 catheter demonstrated greater efficacy than the PENTARAY catheter in terms of shorter mapping time (606 ± 99 vs. 782 ± 211 s, p = .008) and more mapping points (3,026 ± 838 vs. 781 ± 342 points, p < .0001). CONCLUSION: The OCTARAY catheter demonstrated higher voltage recordings, narrower low-voltage areas, and a more efficacious mapping procedure than the PENTARAY catheter.

Prognostic impact of atrial cardiomyopathy: Long-term follow-up of patients with and without low-voltage areas following atrial fibrillation ablation.

BACKGROUND: Atrial cardiomyopathy is known as an underlying pathophysiological factor in the majority of patients with atrial fibrillation (AF). Left atrial low-voltage areas (LVAs) are reported to coincide with fibrosis and likely represent atrial cardiomyopathy. OBJECTIVE: The purpose of this study was to delineate differences in the long-term prognosis of patients stratified by the size of LVAs. METHODS: This observational study included 1488 consecutive patients undergoing initial ablation for AF. LVAs were defined as regions with a bipolar peak-to-peak voltage <0.50 mV. The total study population was divided into 3 groups stratified by LVA size: patients with no LVAs (n = 1136); those with small (<20 cm2) LVAs (n = 250) LVAs; and those with extensive (≥20 cm2) LVAs (n = 102). Composite endpoints of death, heart failure, and stroke were followed for up to 5 years. RESULTS: Composite endpoints developed in 105 of 1488 patients (7.1%), and AF recurrence occurred in 410 (27.6%). Composite endpoints developed more frequently in the order of patients with extensive LVAs (19.1%), small LVAs (10.8%), and no LVAs (5.1%) (P for trend <.0001). Multivariable analysis revealed that LVA presence was independently associated with higher incidence of composite endpoints, irrespective of AF recurrence (modified hazard ratio 1.73; 95% confidence interval 1.13-2.64; P = .011) CONCLUSION: LVA presence and its extent both were associated with poor long-term composite endpoints of death, heart failure, and stroke, irrespective of AF recurrence or other confounders. Underlying atrial cardiomyopathy seems to define a poor prognosis after AF ablation.

Novel Universal Bond Containing Bioactive Monomer Promotes Odontoblast Differentiation In Vitro.

The development of multifunctional materials has been expected in dentistry. This study investigated the effects of a novel universal bond containing a bioactive monomer, calcium 4-methacryloxyethyl trimellitic acid (CMET), on odontoblast differentiation in vitro. Eluates from bioactive universal bond with CMET (BA (+), BA bond), bioactive universal bond without CMET (BA (-)), and Scotchbond Universal Plus adhesive (SC, 3M ESPE, USA) were added to the culture medium of the rat odontoblast-like cell line MDPC-23. Then, cell proliferation, differentiation, and mineralization were examined. Statistical analyses were performed using a one-way ANOVA and Tukey's HSDtest. The cell counting kit-8 assay and alkaline phosphatase (ALP) assay showed that cell proliferation and ALP were significantly higher in the 0.5% BA (+) group than in the other groups. In a real-time reverse-transcription polymerase chain reaction, mRNA expression of the odontogenic markers, dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), was significantly higher in the 0.5% BA (+) group than in the BA (-) and SC groups. Calcific nodule formation in MDPC-23 cells was accelerated in the BA (+) group in a dose-dependent manner (p < 0.01); however, no such effect was observed in the BA (-) and SC groups. Thus, the BA bond shows excellent potential for dentin regeneration.

Possible intermediate quantum spin liquid phase in α-RuCl3 under high magnetic fields up to 100 T.

Pursuing the exotic quantum spin liquid (QSL) state in the Kitaev material α-RuCl3 has intrigued great research interest recently. A fascinating question is on the possible existence of a field-induced QSL phase in this compound. Here we perform high-field magnetization measurements of α-RuCl3 up to 102 T employing the non-destructive and destructive pulsed magnets. Under the out-of-plane field along the c* axis (i.e., perpendicular to the honeycomb plane), two quantum phase transitions are uncovered at respectively 35 T and about 83 T, between which lies an intermediate phase as the predicted QSL. This is in sharp contrast to the case with in-plane fields, where a single transition is found at around 7 T and the intermediate QSL phase is absent instead. By measuring the magnetization data with fields tilted from the c* axis up to 90° (i.e., in-plane direction), we obtain the field-angle phase diagram that contains the zigzag, paramagnetic, and QSL phases. Based on the K-J-Γ-[Formula: see text] model for α-RuCl3 with a large Kitaev term we perform density matrix renormalization group simulations and reproduce the quantum phase diagram in excellent agreement with experiments.

Long-Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST-PVI Trial.

Background An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results We conducted an extended follow-up of the multicenter randomized controlled EARNEST-PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12-month rhythm outcomes in patients with persistent AF between patients randomized to a PVI-alone strategy (n=248) or PVI-plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow-up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on-treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI-plus group than the PVI-alone group (29.0% versus 37.5%, P=0.036). On-treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, P=0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, P=0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, P<0.0001). Conclusions Left atrial ablation in addition to PVI was efficacious during 3-year follow-up. Linear ablation was superior to other ablation strategies but may increase iatrogenic ATs. Registration URL: http://www.umin.ac.jp/ctr/index-j.htm; Unique identifier: UMIN000019449.

Signatures of a magnetic superstructure phase induced by ultrahigh magnetic fields in a breathing pyrochlore antiferromagnet.

The mutual coupling of spin and lattice degrees of freedom is ubiquitous in magnetic materials and potentially creates exotic magnetic states in response to the external magnetic field. Particularly, geometrically frustrated magnets serve as a fertile playground for realizing magnetic superstructure phases. Here, we observe an unconventional two-step magnetostructural transition prior to a half-magnetization plateau in a breathing pyrochlore chromium spinel by means of state-of-the-art magnetization and magnetostriction measurements in ultrahigh magnetic fields available up to 600 T. Considering a microscopic magnetoelastic theory, the intermediate-field phase can be assigned to a magnetic superstructure with a three-dimensional periodic array of 3-up-1-down and canted 2-up-2-down spin molecules. We attribute the emergence of the magnetic superstructure to a unique combination of the strong spin-lattice coupling and large breathing anisotropy.

Gender Differences in Atrial Fibrosis and Cardiomyopathy Assessed by Left Atrial Low-Voltage Areas During Catheter Ablation of Atrial Fibrillation.

Atrial myocardial degeneration predisposes to atrial fibrillation (AF), ischemic stroke, and heart failure. Studies suggest the presence of gender differences in atrial myocardial degeneration. This study aimed to delineate gender differences in the prevalence, predictors, and prognostic impact of left atrial low-voltage areas (LVAs). This observational study included 1,488 consecutive patients who underwent initial ablation for AF. Voltage mapping was performed after pulmonary vein isolation during sinus rhythm. LVAs were defined as regions where bipolar peak-to-peak voltage was <0.50 mV. LVA prevalence was higher in women (38.7%) than in men (16.0%). High age, persistent form of AF, diabetes mellitus, and a large left atrium were shown to be common predictors in both gender categories. Heart failure and history of stroke/thromboembolic events were men-specific predictors of LVA existence. Women experienced more AF recurrence than men (31.1% vs 25.7%, p = 0.027). LVA existence was significantly associated with increased AF recurrence in each gender category, with a respective hazard ratio, 95% confidence interval, and p value of 2.45, 1.87 to 3.22, and <0.0001 in men and 1.82, 1.33 to 2.49, and <0.0001 in women. In conclusion, LVA was more frequent in women than men, and predicted frequent AF recurrence irrespective of gender category.