Influence of ultrasound transmit frequency on measurement of global longitudinal strain on 2D speckle tracking echocardiography.

The reproducibility of longitudinal strain measured by 2D speckle tracking echocardiography (2DSTE) may be affected by ultrasound settings. This study investigated the effect of transmit ultrasound frequency on global longitudinal strain (GLS) by 2DSTE. Apical, 2- and 4-chamber, and long-axis views were obtained in consecutive 162 patients using Philips ultrasound devices. Three different frequency presets were used sequentially: high resolution (HRES, 1.9 to 2.1 MHz), general (HGEN, 1.6 to 1.8 MHz), and penetration mode (HPEN, 1.3 to 1.6 MHz). GLS values were determined for each preset using the Philips Q-station software, resulting in GLS-HRES, GLS-HGEN, and GLS-HPEN. Among the 151 patients with successfully measured GLS, a significant difference in GLS was observed among the three presets (p < 0.0001). GLS-HRES (- 17.9 ± 4.4%) showed a slightly smaller magnitude compared to GLS-HGEN (- 18.8 ± 4.5%, p < 0.0001) and GLS-HPEN (- 18.8 ± 4.5%, p < 0.0001), with absolute differences of 1.1 ± 1.0% and 1.1 ± 1.2%, respectively. This variation in GLS with frequency was evident in patients with both optimal (n = 104) and suboptimal (n = 47) image quality and remained consistent regardless of ultrasound devices, ischemic etiology, or ejection fraction. In conclusion, ultrasound frequency had only a modest effect on GLS measurements. GLS may be reliably assessed in most cases regardless of the ultrasound frequency used.

Recurrence as isthmus-related atrial tachycardia: A cautionary point of low-voltage area homogenization of persistent atrial fibrillation.

A 66-year-old female underwent persistent atrial fibrillation ablation. After pulmonary vein isolation and homogenization of low-voltage areas (LVAs), atrial tachycardia (AT) was not induced at the first session; however, it recurred one year after the procedure. During the second session, the extensive LVAs were distributed in the same area of the left atrial anterior wall and expanded possibly due to the previous LVA homogenization. The activation map revealed a macroreentrant AT circuit with the critical isthmus between the isolated right superior pulmonary vein and homogenized LVAs. Although the Ripple map algorithm failed to visualize dynamic bars, extremely low voltage and fractionated potentials (amplitude, 0.04 mV) were observed at the isthmus. Currently, there are various procedural endpoints of LVA-guided ablation (e.g. local electrogram reduction > 50 % or <0.1 mV in amplitude). In this case, incomplete transmural lesions may have led to slow conduction, which could have become an AT substrate. In cases with extensive LVAs on the left atrial anterior wall, eliminating any potential channels may be important for preventing future iatrogenic ATs. LVA-guided ablation should be performed on an individual basis, considering the potential benefits and harms based on the extent and location of LVAs. Learning objective: Currently, the procedural endpoint of low-voltage area (LVA)-guided ablation varies across studies. Because any low-voltage potentials, except scars, can cause slow conduction, LVA-guided ablation with an endpoint of local electrogram voltage reduction can unintentionally generate an iatrogenic slow conduction isthmus. LVA-guided ablation should be individually performed, considering the potential benefits and harms based on the extent and location of LVAs.

Sleep apnea severity in patients undergoing atrial fibrillation ablation: Home sleep apnea-test and polysomnography comparison.

Background: Sleep apnea (SA) is highly prevalent and should be treated in patients referred for catheter ablation (CA) of atrial fibrillation (AF). Watch-type peripheral arterial tonometry (WP) for home SA testing has demonstrated a high correlation of the apnea-hypopnea index (AHI) with Polysomnography (PSG), but the evidence of its accuracy in AF patients is not adequate. Methods: This study was conducted under a retrospective, single-center, observational design. We included 464 consecutive AF patients (age 65 ± 11 years, 76.5% male, 45.0% paroxysmal-AF) who received both WP and PSG during the periprocedural period of the CA. We compared the AHI using the WP (WP-AHI) to that using PSG (PSG-AHI). Results: The WP-AHI was 25.9 ± 12.7 and PSG-AHI 31.4 ± 18.9 (r = .48). Among 325 patients with a WP-AHI < 30, 116 (35.7%) exhibited a PSG-AHI ≥ 30. Only 12.5% of the patients were indicated for continuous positive airway pressure (CPAP) treatment only by the WP-AHI, while 70.9% were indicated for CPAP by the PSG-AHI according to the Japanese health insurance system. The best cut-off value of the WP-AHI was 18.1 to predict a PSG-AHI ≥ 20 with an area under the curve of 0.72 (95% confidence interval, 0.67-0.76). Conclusions: The WP-AHI and PSG-AHI were weakly correlated in AF patients receiving CA. About one-third of the patients with moderate SA using the WP was diagnosed with severe SA evaluated by PSG. The majority required PSG for the CPAP indication.

Validity of functional assessment for control of trunk in patients with subacute stroke: a multicenter, cross-sectional study.

[Purpose] The purpose of this study was to clarify the criterion validity, construct validity, and feasibility of the Functional Assessment for Control of Trunk (FACT). [Participants and Methods] This study was a multicenter, cross-sectional study of patients with subacute stroke at three Japanese rehabilitation hospitals. To clarify feasibility, we examined the differences in the measurement time between FACT and the Trunk Impairment Scale (TIS). For the criterion validity of FACT, correlations between FACT, TIS, and the trunk items of the Stroke Impairment Assessment Set (SIAS) were examined using Spearman's rank correlation coefficient. For the construct validity of FACT, we examined the correlations with the other assessments. [Results] Seventy-three patients participated in this study. The measurement time was significantly shorter for FACT (212.6 ± 79.2 s) than TIS (372.4 ± 199.6 s). For criterion validity, FACT correlated significantly with TIS (r=0.896) and two SIAS trunk items (r=0.453, 0.594). For construct validity, significant correlations were found for FACT and other tests (r=0.249-0.797). Areas under the curve for FACT and TIS were 0.809 and 0.812, respectively, and the cutoff values for walking independence were 9 and 13 points, respectively. [Conclusion] For inpatients with stroke, FACT offered feasibility, criterion validity, and construct validity.

Impact of Residual Functional Mitral Regurgitation After Atrial Fibrillation Ablation on Clinical Outcomes in Patients With Left Ventricular Systolic Dysfunction.

Functional mitral regurgitation (FMR) negatively impacts the prognosis in patients with atrial fibrillation (AF) and reduced left ventricular (LV) ejection fraction (LVEF). Although structural reverse remodeling after AF ablation can reduce FMR severity, the prognostic impact of FMR and its evolution remain unclear. Of 491 patients with baseline LVEF <50% who underwent first-time AF ablation, 134 patients (27%) had grade 2 to 4 FMR at baseline. Among them, 88 patients (66%) exhibited FMR improvement to grade 0 to 1 FMR 6 months after AF ablation. Conversely, among 357 with baseline grade 0 to 1 FMR, 13 patients (3.6%) exhibited FMR worsening to grade 2 to 4 FMR despite AF ablation. Assessment with multidetector computed tomography revealed that an increase in the left atrial emptying fraction (odds ratio 3.55 per 10% increase; 95% confidence interval 2.12 to 5.95) and a reduction in the LV end-diastolic volume index (1.35 per 10-ml/m2 decrease; 1.04 to 1.76) were identified as contributors to the FMR improvement. During a follow-up of 43 months, patients with postprocedural grade 2 to 4 FMR more frequently experienced hospitalizations for heart failure or cardiovascular death than those with grade 0 to 1 FMR (30.5% vs 4.6%, log-rank p <0.001). An age-adjusted multivariate Cox regression analysis including baseline and postprocedural FMR revealed that postprocedural grade 2 to 4 FMR (hazard ratio, 3.24; 95% confidence interval 1.43 to 7.35) was significantly associated with unfavorable events. In conclusion, AF ablation modified and often improved FMR severity in patients with reduced LVEF. Residual grade 2 to 4 FMR 6 months after AF ablation was associated with a poor prognosis.

Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts.

BACKGROUND: Peritoneal metastasis (PM) is one of the most common causes of noncurative surgery and the most frequent recurrence pattern in gastric cancer (GC). During the process of PM, GC cells detached from primary tumor interact with human peritoneal mesothelial cells (HPMC) overlapped with adipose tissues such as the omentum or mesentery. Although the interaction with HPMC promotes the malignancy of GC, the role of adipose tissues remains unclear. AIMS: We aimed to clarify how adipose tissue are affected by adjacent primary tumors during the expression of adipokines and to elucidate whether GC cells transform adipocytes into CAFs in vitro. In addition, we investigated whether GC cells are affected by adipocytes in their ability to infiltrate. METHODS: We investigated the phenotypic conversion of adipocytes during the malignant process of GC cells in vivo and in vitro. We evaluated the expression levels of adiponectin in the omental adipose tissue of gastric cancer patients by western blotting. Following adipocytes/gastric cancer cells coculture, adipocyte markers, adiponectin receptors, and inflammatory cytokine markers were detected by real-time PCR and/or western blotting in the single-cultured and co-cultured adipocytes; cancer-associated fibroblast (CAF) markers were detected by immunofluorescence and western blotting in the single-cultured and co-cultured adipocytes; invasion assays were performed in single cultured and co-cultured MKN45 and OCUM. RESULTS: In omental adipose tissues that are situated close to the primary tumors, the expression of adiponectin tended to decrease in patients with subserosal or serosal invasion. By co-culturing with GC cells, adipocytes were dedifferentiated and the expression levels of CAF marker FSP1 and inflammatory cytokines, PAI-1 and IL-6, significantly increased (p < 0.05). Furthermore, GC cells co-cultured with adipocytes showed enhanced invasion ability. CONCLUSION: Our findings suggest that the phenotypic conversion of adipocytes may promote the malignancy of GC in the construction of the cancer microenvironment of PM.

Hypoxia-Induced CD36 Expression in Gastric Cancer Cells Promotes Peritoneal Metastasis via Fatty Acid Uptake.

BACKGROUND: The lipid scavenger receptor cluster of differentiation 36 (CD36) has been shown to have a pro-metastatic function in several cancers. Adipose tissue, a favorable site for peritoneal metastasis (PM) from gastric cancer (GC), promotes this process by providing free fatty acids (FFAs); however, the role of CD36 in PM progression from GC remains to be elucidated. MATERIALS AND METHODS: We evaluated CD36 expression in the GC cells under various conditions. CD36 overexpressing (CD36OE) MKN45 cells were prepared and their migration and invasive properties were assessed. A PM mouse model was used to investigate the biological effects of palmitic acid (PA) and CD36. Furthermore, we examined the clinical role of CD36 expression in 82 human PM samples by immunohistochemical staining. RESULTS: Hypoxia markedly increased CD36 expression in GC cells. In normoxia, only CD36OE MKN45 cells treated with PA showed an increase in migration and invasion abilities. An increased expression of active Rac1 and Cdc42 was observed, which decreased following etomoxir treatment. Conversely, hypoxia increased those capacities of both vector and CD36OE MKN45 cells. In a mouse model transplanted with CD36OE MKN45 cells, more peritoneal tumors were observed in the high-fat diet group than those in the normal diet group. In clinical samples, 80% of PM lesions expressed CD36, consistent with hypoxic regions, indicating a significant association with prognosis. CONCLUSION: Our findings indicate that a hypoxia in the peritoneal cavity induces CD36 expression in GC cells, which contributes to PM through the uptake of FFAs.

Crosstalk between cancer-associated fibroblasts and immune cells in peritoneal metastasis: inhibition in the migration of M2 macrophages and mast cells by Tranilast.

BACKGROUND: The role of tumor-stroma interactions in tumor immune microenvironment (TME) is attracting attention. We have previously reported that cancer-associated fibroblasts (CAFs) contribute to the progression of peritoneal metastasis (PM) in gastric cancer (GC), and M2 macrophages and mast cells also contribute to TME of PM. To elucidate the role of CAFs in TME, we established an immunocompetent mouse PM model with fibrosis, which reflects clinical features of TME. However, the involvement of CAFs in the immunosuppressive microenvironment remains unclear. In this study, we investigated the efficacy of Tranilast at modifying this immune tolerance by suppressing CAFs. METHODS: The interaction between mouse myofibroblast cell line LmcMF and mouse GC cell line YTN16 on M2 macrophage migration was investigated, and the inhibitory effect of Tranilast was examined in vitro. Using C57BL/6J mouse PM model established using YTN16 with co-inoculation of LmcMF, TME of resected PM treated with or without Tranilast was analyzed by immunohistochemistry. RESULTS: The addition of YTN16 cell-conditioned medium to LmcMF cells enhanced CXCL12 expression and stimulated M2 macrophage migration, whereas Tranilast inhibited the migration ability of M2 macrophages by suppressing CXCL12 secretion from LmcMF. In PM model, Tranilast inhibited tumor growth and fibrosis, M2 macrophage, and mast cell infiltration and significantly promoted CD8 + lymphocyte infiltration into the tumor, leading to apoptosis of cancer cells by an immune response. CONCLUSION: Tranilast improved the immunosuppressive microenvironment by inhibiting CAF function in a mouse PM model. Tranilast is thus a promising candidate for the treatment of PM.

Decrease in red cell distribution width as a useful predictor of success after catheter ablation for atrial fibrillation: a retrospective multi-center study.

Red cell distribution width (RDW) is reportedly associated with cardiovascular events, including atrial fibrillation (AF). We investigated whether the RDW values were associated with the outcomes of catheter ablation for AF. This retrospective multicenter study included 501 patients with AF (239 paroxysmal AF cases, 196 persistent AF cases, and 66 long-standing persistent AF cases) who underwent initial AF ablation between March 2017 and May 2018. The RDW values were evaluated before and at 1-3 months after the procedure. The patients were stratified based on the recurrence of AF within 1 year after the index procedure with a blanking period of 3 months into recurrence group (107 patients, 21.4%) and no-recurrence group (394 patients, 78.6%). There were no significant differences in preoperative RDW values between the groups (p = 0.37). The RDW value did not change significantly after the ablation in the recurrence group (13.55-13.60%, p = 0.37), although it decreased significantly in the no-recurrence group (13.64-13.37%, p < 0.001). Multivariate Cox proportional hazards regression analyses revealed that a postoperative change in RDW (ΔRDW) was independently associated with AF recurrence (hazard ratio 2.00, 95% confidence interval 1.42-2.76, p < 0.001). Receiver operating characteristic curve analysis revealed that a ΔRDW cut-off value of - 0.1% provided a c-statistic of 0.65 for predicting AF recurrence. Decrease in RDW during the blanking period after ablation independently predicted the 1-year success of AF ablation.

Characterizing clinical outcomes and factors associated with conduction gaps in VISITAG SURPOINT-guided catheter ablation for atrial fibrillation.

PURPOSE: Although usefulness of VISITAG SURPOINT (VS) on pulmonary vein isolation (PVI) in catheter ablation of atrial fibrillation has been reported, optimal VS thresholds can depend on the inter-tag distance (ITD) and vice versa. We validated the efficacy of PVI with lower target ITDs and VS values than in previous studies. METHODS: Retrospective review of consecutive patients (N = 100) with paroxysmal (n = 32) or persistent AF (n = 68) undergoing VS-guided ablation between 09/2018 and 08/2019 was conducted. All procedures were performed by two operators. Target VS values were 425 (anterior), 375 (posterior), and 325 (near the esophagus). Target ITD was 4 mm. RESULTS: Acute PVI was achieved in all cases, however, 13 residual gaps in 12 patients were observed after initial encirclement (first pass isolation: 88%). Ten gaps due to spontaneous PV reconnections (PVR) were found in nine patients (9%). These 23 gaps had similar median VS (gap-related vs non-gap: 429 vs 410, P = .4545) and power (36 vs 36W, P = .4843), higher contact force (13.8 vs 11.0g, P = .0061), and larger ITD (5.3 vs 3.7mm, P < .001) when compared to the remaining tags. Only ITDs were independently associated with gap formation in multivariate analysis. One-year Kaplan-Meier freedom from any atrial arrhythmia was 87.2%. Eight patients received repeat ablation (8.1%) and of these, 6 (75%) were free from PVR. CONCLUSION: Favorable rates of first pass isolation, acute PVR, and long-term procedure success were achieved using lower VS values than in previous reports. With a target VS value of 375-425, ITDs of 4 mm was sufficient for durable PVI.

Glial cell type-specific gene expression in the mouse cerebrum using the piggyBac system and in utero electroporation.

Glial cells such as astrocytes and oligodendrocytes play crucial roles in the central nervous system. To investigate the molecular mechanisms underlying the development and the biological functions of glial cells, simple and rapid techniques for glial cell-specific genetic manipulation in the mouse cerebrum would be valuable. Here we uncovered that the Gfa2 promoter is suitable for selective gene expression in astrocytes when used with the piggyBac system and in utero electroporation. In contrast, the Blbp promoter, which has been used to induce astrocyte-specific gene expression in transgenic mice, did not result in astrocyte-specific gene expression. We also identified the Plp1 and Mbp promoters could be used with the piggyBac system and in utero electroporation to induce selective gene expression in oligodendrocytes. Furthermore, using our technique, neuron-astrocyte or neuron-oligodendrocyte interactions can be visualized by labeling neurons, astrocytes and oligodendrocytes differentially. Our study provides a fundamental basis for specific transgene expression in astrocytes and/or oligodendrocytes in the mouse cerebrum.

Usefulness of Post-Procedural Plasma Brain Natriuretic Peptide Levels to Predict Recurrence After Catheter Ablation of Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction.

Catheter ablation (CA) of atrial fibrillation (AF) improves cardiac function, resulting in a decrease in plasma brain natriuretic peptide (BNP) levels in patients with reduced left ventricular ejection fraction (LVEF). This study sought to examine the pre-procedural and post-procedural correlations between BNP levels and cardiac function and the associations between the BNP levels and recurrence after CA in patients with AF and reduced LVEF. Of 3142 consecutive patients who underwent first-time CA of AF at our institute, a total of 217 patients with LVEF <50% were enrolled. Significant decrease in BNP levels (from a median of 198 [interquartile range 113 to 355] to 47.7 [22.7 to 135] pg/ml, p <0.001) and improvement in LVEF (from 39±9% to 61±16%, p <0.001) were observed 3 months after CA. There was a linear correlation between log-transformed BNP levels and cardiac measures (LVEF: r = -0.64; LV end-diastolic volume: r = 0.25; LV end-systolic volume: r = 0.43; left atrial volume: r = 0.52; all p <0.001). During a median follow-up of 35 months, AF recurrence after a 3-month blanking period was observed in 80 patients (37%). Cox proportional hazard regression analysis after adjustment for cardiac measures significant in univariate analysis revealed that early recurrence within the blanking period (hazard ratio, 4.88; 95% confidence interval, 2.89 to 8.25) and elevated post-procedural BNP levels (2.02 per unit log increase; 1.14 to 3.56) were significant predictors of AF recurrence, but pre-procedural BNP was not. In conclusion, post-procedural BNP levels at the end of the blanking period predicted subsequent AF recurrence in patients with reduced LVEF, independent of early recurrence.