Search

Direct comparison studies about the incidence of esophagogastric complications between radiofrequency (RF) and cryoballoon (CB) catheter ablation (CA) for atrial fibrillation (AF) have been scarce. We sought to elucidate the relationship between the pulmonary vein isolation (PVI) modalities and esophagogastric complications.The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 160 patients were enrolled and divided into the RF and CB groups. Esophageal ulcers, gastric hypomotility, and exfoliative esophagitis detected by esophagogastroduodenoscopy were defined as esophagogastric complications in this study.The median age was 68 years old, with 34% being females. Esophagogastric complications were observed in 42.5% of patients who underwent CA. According to the detailed esophagogastric complications, the RF group had a higher prevalence of esophageal ulcers than the CB group (19% vs. 0%, p .0001). There was no significant difference between the two groups regarding gastric hypomotility and exfoliative esophagitis (18% vs. 28%; p = .15 and 16% vs. 21%; p = .42, respectively).Asymptomatic esophagogastric complications were common in CA for AF. The incidence of esophageal ulcers was higher in the RF group than in the CB group, whereas the other esophagogastric complications did not significantly differ.

Purpose Although the impairment of regulatory T-cells (Tregs) has been shown in the liver or portal area of biliary atresia (BA) the frequency and function of circulating Tregs in BA patients is poorly understood. We aimed to investigate the frequency and function of circulating Tregs in BA patients. Methods Peripheral blood mononuclear cells were collected from 25 BA patients and 24 controls. Treg frequency was measured by flow cytometry; function was determined by T-cell proliferation assay. We also assessed the association between Treg frequency/function and clinical parameters in BA cases. Results There was no significant difference between the two groups in both frequency (BA: 3.4%; control: 3.2%; p = 0.97) and function (BA: 22.0%; control: 7.5%; p = 0.23) of Tregs. We further focused on 13 preoperative BA patients and 14 age-matched controls. Neither Treg frequency nor function were significantly different (frequency: BA: 4.6%; control: 3.4%; p = 0.38, function: BA: 2.7%; control: 7.6%; p = 0.89). There was no association between Treg frequency/function and clinical parameters. Conclusion Neither the frequency nor function of circulating Tregs was affected in BA patients, suggesting the negative role of circulating Tregs in the pathogenesis of BA. Further investigation of local Treg profiles is warranted.

The mechanical properties of the myocardium in the left ventricle and right atrium were estimated by simultaneously measuring the local impedance (LI) and contact force (CF) using an ablation catheter. Radiofrequency catheter ablation (RFCA) is a well-established arrhythmia treatment. Monitoring the RF power, CF and properties of myocardium during RFCA are necessary to estimate the effect of ablation. Indices, such as CF, lesion size index and ablation index, do not include the myocardium mechanical properties. Therefore, there is the risk of side effects, such as cardiac tamponade, by excessive catheter indentation into vulnerable areas. We propose the simultaneous measurement of LI and CF for estimating the myocardial mechanical properties to reduce the side effects. In this study, an

Background: The incidence of new-onset atrial high-rate episode (AHRE) is higher among patients with cardiac implantable electronic devices (CIEDs) than in the general population. We sought to elucidate the clinical factors associated with AHRE in CIED patients, including P-wave dispersion (PWD) in sinus rhythm. Methods and Results: In all, 101 patients with CIEDs newly implanted between 2010 and 2014 were included in the study. PWD was measured at the time of device implantation via a body-surface electrocardiogram. AHRE was defined as any episode of sustained atrial tachyarrhythmia (>170 beats/min) recorded in the device's memory. Patients were divided into an AHRE (n=34) and non-AHRE (n=67) group based on the presence or absence of AHRE within 1 year of device implantation and compared. Mean (±SD) patient age was 75±11 years. A greater incidence of sick sinus syndrome (P=0.05) and longer PWD (62.6±13.1 vs. 38.2±13.9 ms; P

A 48-year-old male with ischemic cardiomyopathy was admitted because of cardiogenic shock due to incessant ventricular tachycardia (VT). Despite the introduction of multiple mechanical cardiac support (MCS) devices, his hemodynamics were unstable; therefore, VT ablation was performed. Due to the limited vascular and left ventricle (LV) access with the multiple MCS devices, only the left femoral artery and vein were accessible. In addition, the transseptal approach as an LV access was difficult because of the MitraClip (Abbott Park, IL, USA). Posterior papillary muscle-origin VT was successfully treated via a transaortic approach under the MCS. After the VT ablation, the patient recovered from the MCS. LEARNING OBJECTIVE: Mechanical cardiac support (MCS) devices are critical during ventricular tachycardia (VT) ablation in patients with left ventricular (LV) dysfunction. However, the ablation strategy for cases with limited access due to multiple MCS devices has not been established. In this case, VT was successfully treated via a transaortic approach using intracardiac echocardiography. The number of cases requiring VT ablation for patients with limited vascular and LV endocardial access would increase; therefore, the accumulation of those cases is required to find a better strategy.

Background Although the lesion size index (LSI) has been well established, it is sometimes difficult to achieve first‐pass pulmonary vein isolation (PVI) and to avoid acute pulmonary vein reconnections, even with LSI‐guided procedures. The purpose of this study was to assess the predictive accuracy of a novel parameter, the optimized lesion size index (o‐LSI), to perform PVI. Methods The voltage maps created by the Advisor™ high‐density (HD) grid catheter before PVI in 35 atrial fibrillation (AF) patients were examined for an association between the voltage amplitude and insufficient ablation sites (IAS), which were defined as either (i) spontaneous reconnection sites, (ii) dormant PV conduction sites unmasked with 20 mg of adenosine triphosphate disodium hydrate (ATP) injection, or (iii) PV‐LA gap sites after the initial PVI. Results IAS was observed in 25/1417 of the total ablation sites. IAS was significantly associated with higher bipolar voltage areas (4.20 ± 2.68 vs 2.43 ± 1.93 mV, P, To achieve first‐pass pulmonary vein isolation (PVI) and to avoid the acute pulmonary vein reconnections is sometimes difficult even with the lesion size index (LSI)‐guided radiofrequency ablation. We focused on the relationship between the optimized ‐LSI (o‐LSI) (LSI/bipolar voltage within the PV‐encircling lines, which were defined by the Advisor™ HD Grid catheter) and the sufficient ablation sites and found that was strongly associated with acute PV reconnection. The o‐LSI may potentially be novel strategies for durable PVI.

The lesion size index (LSI) predicts radiofrequency (RF) ablation lesion size and is an established parameter for pulmonary vein isolation. However, the effectiveness and safety of LSI for cavotricuspid isthmus (CTI) linear ablation remain unclear.This single-center retrospective study included 50 of patients (67 ± 10 years, 68% male) who underwent de novo CTI linear ablation between July 2020 and December 2020. The LSI target was set at 5.0 and 4.0 for the anteriorAcute bidirectional CTI block was achieved in all patients with an RF application time of 4.0 min (3.1-5.0 min), RF application number of 15 ± 7, and length of CTI of 36.9 ± 9.3 mm. First-pass bidirectional conduction block of the CTI was achieved in 39/50 (78%) patients. No major complications were observed. The contact force (CF) per application was significantly lower in the gap tag group than in the non-gap tag group (7 g [7-8 g] vs. 10 g [7-12 g], P = 0.0284).LSI-guided CTI linear ablation is an effective and safe treatment approach. CF affects gap formation, even when the target LSI is the same.

Background Right ventricular (RV) pacing causes left ventricular (LV) dyssynchrony sometimes resulting in pacing‐induced cardiomyopathy. However, RV pacing for hypertrophic obstructive cardiomyopathy is one of the treatment options. LV flow energy loss (EL) using vector flow mapping (VFM) is a novel hemodynamic index for assessing cardiac function. Our study aimed to elucidate the impact of RV pacing on EL in normal LV function and hypertrophic cardiomyopathy (HCM) patients. Methods A total of 36 patients with dual‐chamber pacemakers for sick sinus syndrome or implantable cardioverter defibrillators for fatal ventricular tachyarrhythmias were enrolled. All patients were divided into two groups: 16 patients with HCM (HCM group) and others (non‐HCM group). The absolute changes in EL under AAI (without RV pacing) and DDD (with RV pacing) modes were assessed using VFM on color Doppler echocardiography. Results In the non‐HCM group, the mean systolic EL significantly increased from the AAI to DDD modes (14.0 ± 7.7 to 17.0 ± 8.6 mW/m, P = .003), whereas the mean diastolic EL did not change (19.0 ± 12.3 to 17.0 ± 14.8 mW/m, P = .231). In the HCM group, the mean systolic EL significantly decreased from the AAI to DDD modes (26.7 ± 14.2 to 21.6 ± 11.9 mW/m, P, In non‐HCM patients, the RV pacing decreased the vortex area and the circulation and in HCM patients, it increased the vortex area and the circulation. The RV pacing significantly increased systolic energy loss in the non‐HCM group (P = .003), but it significantly decreased in the HCM group (P

Introduction The incidence of new-onset atrial high-rate episode (AHRE) is higher among patients with cardiac implantable electronic devices (CIEDs) than in the general population. We sought to elucidate the clinical factors including P-wave dispersion (PWD) in sinus rhythm associated with AHRE in CIED patients. Methods and results One hundred one patients with newly implanted CIEDs from 2010 to 2014 at our institute were included. PWD was measured at the time of device implantation via a body-surface electrocardiogram. AHRE was defined as any episode of sustained atrial tachyarrhythmia (>170 bpm) recorded in the device’s memory. Patients were divided into an AHRE group (n=34) and non-AHRE group (n=67) in accordance with the presence or absence of AHRE within one year of device implantation and compared. The mean age was 75 ± 11 years old. A greater incidence of sick sinus syndrome (p=0.05) and longer PWD (62.6 ± 13.1 vs. 38.2 ± 13.9 ms; p

We prospectively collected device and heart rate data through remote monitoring (RM) of patients with an implantable cardioverter defibrillator (ICD). The objective was to identify the predictors of lethal arrhythmic events (VT/VF).Thirty-three patients (mean age: 50 years) with ICDs [with functionality of heart rate variability (HRV) analysis] were divided into two groups [VT/VF (+), VT/VF (-) ]. Clinical, device (ventricular lead impedance; amplitude of ventricular electrogram), and HRV data were compared between the two groups. The NN interval-index (SDNNi) was calculated for every 5 minutes, and the mean, maximum, minimum, and standard deviation of SDNNi during the 24-hour period were used.During the observation period of 13 ± 10 months, 10 patients experienced VT/VF events. Total mean, max, and min SDNNi were higher in the VT/VF (+) than the VT/VF (-) group (132.9 ± 9.3 versus 93.5 ± 6.1, P = 0.0013; 214.6 ± 10.6 versus 167.0 ± 7.0, P = 0.0007; 71.2 ± 7.5 versus 43.9 ± 4.9, P = 0.0047). On logistic regression analysis, a total mean SDNNi of 100.1, max SDNNi of 185.0 and min SDNNi of 52.0 as cut-off values for prediction of a VT/VF event demonstrated significant receiver operating characteristic (ROC) curves (AUC = 0.86, P = 0.0007; AUC = 0.84, P = 0.0005; AUC = 0.78, P = 0.0030). The max ΔSDNNi, i.e., difference from baseline SDNNi, and min ΔSDNNi in 7 and 28 days preceding VT/VF events were significant predictors of VT/VF events.Time-domain HRV analysis through a RM system may help identify patients at high risk of lethal arrhythmic events; in addition, it may help predict the occurrence of lethal arrhythmic events in specific cases.

Ablation index (AI) is a useful tool of the CARTO® system to make effective lesions during pulmonary vein isolation (PVI) for atrial fibrillation (AF). However, the optimal distance between neighboring ablation points (interlesion distance (ILD)) is still unclear. Here, we evaluated the optimal ILDs in the AI-guided PVI. Forty-nine AF patients who underwent AI-guided PVI in our institute from July 2018 to March 2019 were retrospectively enrolled in this study. Target AI was set at 500 and 400 for anterior and posterior walls, respectively, and we compared the ILDs with and without electrical gaps after a first encircling PVI. In both PV, the ILDs with electrical gaps were longer than those without electrical gaps. The best cutoff values of ILD to detect the electrical gaps using the ROC curve were 5.4 mm for the RPV anterior wall (AUC, 0.67; sensitivity, 0.42; specificity, 0.84, P < 0.01) and 4.4 mm for the RPV posterior wall (AUC, 0.68; sensitivity, 0.91; specificity, 0.39, P < 0.01). Similarly, the best cutoff values of ILD were 5.5 mm for the LPV anterior wall (AUC, 0.74; sensitivity, 0.65; specificity, 0.82, P < 0.01) and 5.1 mm for the LPV posterior wall (AUC, 0.67; sensitivity, 0.79; specificity, 0.53, P =0.03). The optimal interlesion distances for PVI were different in each PV segment. To achieve the first-pass isolation, less than 5.4/4.4 mm for the RPV anterior/posterior and 5.5/5.1 mm for the LPV anterior/posterior walls of interlesion distances were the best cutoff values in the patients with AF.

Complex atrial tachycardias (ATs) after catheter ablation or a MAZE procedure is sometimes difficult to determine the circuits of the tachycardia. A high-density, grid-shapes mapping catheter has been launched, which can be useful for detecting the detail circuits of tachycardias on three-dimensional mapping systems. The signal quality is also important for performing electrophysiological studies (EPSs), such as entrainment mapping, to identify the circuit. This unique mapping catheter has 1 mm electrodes on 2.5 Fr shafts, which improve the signal quality. The high-quality intracardiac electrograms facilitate differentiating small critical potentials, which allows us to perform detailed entrainment mapping in targeted narrow areas. Here, we describe a patient with a perimetral AT with epi-endocardium breakthrough after a MAZE surgery and catheter ablation, which was treated successfully along with detailed entrainment mapping using the HD Grid. This catheter with high-quality signals could be a significant diagnostic tool for a classic EPS as well as for the construction of 3D mapping.

Background: The wearable cardioverter defibrillator (WCD) has been available since 2014 in Japan, and its benefit in the in-hospital acute phase at high risk of ventricular tachyarrhythmia (VTA) has been established, but its clinical use in the outpatient setting remains unclear, especially in Japan. Methods and Results: The subjects consisted of 43 consecutive patients with WCD use in the outpatient setting from April 2014 to October 2019 at the present institute. Event alerts and wearing compliance were checked via the remote monitoring system, and a dedicated WCD training team contacted the patients if necessary. The median observation period was 51 days (IQR, 37–68 days) and the median daily wearing time was 23.1 h/day (IQR, 22.0–23.6 h/day). WCD was prescribed for primary prevention of VTA in 7 patients (16%), and for secondary prevention in 36 (84%). The common reason for WCD use was preventive therapy and/or clinical observation. Two appropriate and one inappropriate shock were observed. Eleven patients were not indicated for ICD because of successful catheter ablation optimal medical therapy, VTA in early onset of heart disease and refusal. The remaining 32 patients, however, underwent ICD implantation. Conclusions: In the present real-world study, the WCD wearing compliance was well-maintained in the outpatient setting. WCD is useful for patients at high risk of VTA.

Background: Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on LI parameters were scarce. This study aimed to evaluate the influence of catheter contact angle on LI change and lesion size in a porcine experimental model. Methods: Lesions were created on porcine myocardial left ventricles by the LI and Contact force(CF)-sensing ablation catheter (INTELLANAV STABLEPOINT™). Radiofrequency ablation was performed with a power of 30 watts and a duration of 30 seconds. CF (0, 5, 10, 20, and 30g) and catheter contact angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise by catheter contact, LI drop by RF application, and lesion size (lesion width, surface width, and lesion depth) were evaluated. Results: The values of LI rise increased as CF increased. Regarding the difference of catheter angles, LI rise with 90° was lower than those with 30°. The LI drop also increased as CF increased in all contact angles. The LI drop with 90° was lower than those with 30° in CF 5, 10, 20, and 30 g, respectively. Maximum lesion width and surface width were smaller in 90° than those in 30°, whereas there were no differences in maximum lesion depth except for CF 5g. The approximate curves were well fitted with a quadratic equation in all angles on LI drop vs. maximum lesion width, and lesion depth. Conclusion: Under the same CF, the values of LI drop and lesion width in 90° were significantly lower than those in 30° despite lesion depths were not different among the three angles. LI drop correlates with lesion width and lesion depth at any angle, which may be a good predictor of lesion size.

Background Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on lesion size and LI drop were scarce. This study aimed to evaluate the influence of catheter contact angle on lesion size and LI drop in a porcine experimental study. Methods Lesions were created on porcine myocardial left ventricles by the LI-sensing ablation catheter (IntellaNav MiFi OI®). Contact force (CF) was measured using pressure to current transducer (load cell). Radiofrequency ablation was performed with a power of 30 Watt and a duration of 30 seconds. CF (0g, 5g, 10g, 20g, and 30g) and catheter angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise, LI drop by RF application, and lesion size (maximum lesion width, maximum surface width, and maximum lesion depth) were evaluated. Results There was no angular dependence in LI rise in all CF. The values of LI rise increased as CF increased. The LI drop also increased as CF increased in all contact angles. Regarding the difference of catheter angles, LI drop with 90° was lower than those with 30° and 45°in CF 10g, 20g, and 30g, respectively. Maximum lesion width and surface width were larger in 30° and 45° than those in 90°, whereas there were no differences in maximum lesion depth. Conclusion LI drop in 90° were significantly lower than those in 45° and 30°. Although lesion depths were not different among the three angles, the absolute values of LI drop were different. Caution should be exercised to comprehend the LI drop with catheter angles. Funding Acknowledgement Type of funding sources: None.

Background Patients with acute aortic dissection (AAD) sometimes are complicated with atrial fibrillation (AF). However, the impact of AF and the use of oral anticoagulation (OAC) on the prognosis of AAD remains unclear. In this study, we evaluated the prognostic impact of AF and OAC therapy in patients with type B AAD. Methods Consecutive patients diagnosed with type B AAD between January 2010 and December 2020 in our university hospital were retrospectively analyzed. All patients were divided into 2 groups based on the concomitance with or without AF. The primary endpoint was set as major adverse cardiovascular events (MACEs), including all-cause death, enlargement of aortic diameter, aortic ruptures, and cerebral infarction. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of clinical events at 1 year. Results A total of 146 patients diagnosed with type B AAD were enrolled, with a mean age of 66±12 years, and 81% of male. Thirty-two patients (22%) experienced MACEs during 272±142 days-observation. Concomitant AF was observed in 27 patients (18%). In the Kaplan-Meier curve analysis, the patients with AF showed significantly higher events than those without AF (log-lank p75 years (HR: 2.635, 95% CI: 1.268–5.388 p=0.011) were independent predictors of MACEs. Regarding OAC in patients with AF, Kaplan-Meier analysis showed that usage of OAC was associated with a higher incidence of MACEs than those without (log-rank, p=0.036) Conclusion Presence of AF, enlargement of descending aorta diameter, and age were independent predictors of future MACEs in patients with type B AAD. Additionally, usage of OAC is associated with MACEs in patients with type B AAD complicated with AF. Funding Acknowledgement Type of funding sources: None.

Background: Local impedance (LI) can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). However, data on the effects of catheter contact angle on LI parameters are scarce. This study aimed to evaluate the influence of catheter contact angle on LI changes and lesion size with 2 different LI-sensing catheters in a porcine experimental study. Methods: Lesions were created by the INTELLANAV MiFi™ OI (MiFi) and the INTELLANAV STABLEPOINT™ (STABLEPOINT). RFCA was performed with 30 watts and a duration of 30 seconds. The CF (0, 5, 10, 20, and 30 g) and catheter contact angle (30°, 45°, and 90°) were changed in each set (n=8 each). The LI rise, LI drop, and lesion size were evaluated. Results: The LI rise increased as CF increased. There was no angular dependence with the LI rise under all CFs in the MiFi. On the other hand, the LI rise at 90° was lower than at 30° under 5 and 10 g of CF in STABLEPOINT. The LI drop increased as CF increased. Regarding the difference in catheter contact angles, the LI drop at 90° was lower than that at 30° for both catheters. The maximum lesion widths and surface widths were smaller at 90° than at 30°, whereas there were no differences in lesion depths. Conclusion: The LI drop and lesion widths at 90° were significantly smaller than those at 30°, although the lesion depths were not different among the 3 angles for the MiFi and STABLEPOINT.

We performed cavotricuspid isthmus (CTI) linear ablation for atrial flutter; however, the tachycardia cycle length was not changed at all. In such cases, repeated or broad line ablation is usually performed. We presented that high-density three-dimensional mapping after the first CTI linear ablation, which revealed the complex tachycardia circuit with the epicardial and endocardial breakthrough.

The recurrence of atrial fibrillation (AF) after catheter ablation (CA) is still an unsolved issue. Although structural remodeling is relatively well defined, the method to assess electrical remodeling of the atrium is not well established. In this study, we evaluated the relationship between atrial conduction properties and recurrence after CA for AF. One hundred six consecutive patients (66 ± 11 years old, male: 68%) who underwent CA for AF with a CARTO system from July 2016 to July 2019 were enrolled in this study. An activation map of both atria was constructed to precisely evaluate the total conduction time, distance, and conduction velocity between the earliest and latest activation sites during sinus rhythm. All parameters were compared between the patients with or without AF recurrence. Of the patients, 27 had an AF recurrence (Rec group). The left atrial (LA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (101.2 ± 17.9 vs. 116.9 ± 18.0 cm/s, P

Background The relationship between atrial high-rate episode (AHRE) burden (i.e., the frequency of atrial tachyarrhythmia) and heart failure (HF) risk is unclear. We hypothesized that new-onset and higher burden of AHRE are associated with HF. Methods and Results: We included 104 consecutive patients with cardiac implantable electronic devices (CIEDs) capable of continuous atrial rhythm monitoring. Patients with AF history were excluded. To stratify patients, AHREs were evaluated only during the initial 1 year after CIED implantation. The primary endpoint was all-cause death or new-onset or worsening HF that required unplanned hospitalization or readjustment of HF drug therapy. At 1 year after CIED implantation, 34/104 patients (33%) exhibited AHREs. No difference in basal clinical characteristics except for left ventricular ejection fraction between patients with and without new-onset AHREs was found. AHRE groups had more HF events than the non-AHRE group. All patients were divided into 3 groups based on AHRE burden: none, low, and high. Worsening HF was observed in 12 patients (12%). Cox hazard analysis revealed that AHRE and higher AHRE burden were independent predictive factors for worsening HF. The high group showed a higher risk for HF than the non-AHRE groups, but no significant difference was found between the low- and non-AHRE groups. Conclusions New-onset higher AHRE burden was associated with subsequent risk for HF in patients with CIEDs.

Background Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium–glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller ( P =0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group ( P =0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group ( P =0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group. Conclusions CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.

Background We prospectively collected device and heart rate data, i.e. heart rate variability (HRV), through remote monitoring (RM) of patients with implantable cardioverter defibrillator (ICD). Several studies have demonstrated usefulness of RM in implanted device patients, however, reports concerning the predictors of lethal ventricular arrhythmias are limited. Purpose The objective was to identify the predictors of lethal arrhythmic events (VT/VF). Methods Thirty-three patients (mean age: 50 years) with ICDs [with functionality of HRV analysis] were divided into 2 groups [VT/VF(+), VT/VF(−)]. Clinical, device (ventricular lead impedance; amplitude of ventricular electrogram), and HRV data were compared between the 2 groups. As the index of time-domain HRV analysis, NN intervals-index (SDNNi) was calculated for every 5 minutes, and the mean, maximum, and minimum SDNNi during the 24-hour period were used. Results During the observation period (median 12 months), 10 patients experienced VT/VF events. In HRV data, the mean, max, and min SDNNi were higher in VT/VF(+) than VT/VF(−) group (132.9±9.3 v.s. 93.5±6.1, p=0.0013; 214.6±10.6 v.s. 167.0±7.0, p=0.0007; 71.2±7.5 v.s. 43.9±4.9, p=0.0047). The other parameters did not exhibit significant difference. On logistic regression analysis, the mean SDNNi of 100.1, max SDNNi of 185.0 and min SDNNi of 52.0 as cut-off values for prediction of VT/VF event demonstrated significant receiver operating characteristics (ROC) curves (AUC=0.86, p=0.0007; AUC=0.84, p=0.0005; AUC=0.78, p=0.0030). Furthermore, in cases of VT/VF(+) group, the max ΔSDNNi, i.e., difference from baseline SDNNi, and min ΔSDNNi in 7 and 28 days preceding VT/VF events exhibited time course changes in comparison with baseline values. They were significant predictors of VT/VF events (max ΔSDNNi cut-off: 46.8, AUC=0.91, p=0.0002; min ΔSDNNi cut-off: −42.4, AUC=0.88, p=0.0014). Conclusion Time-domain analysis of HRV through RM may help identify patients at high risk of lethal arrhythmic events, and predict occurrence of such arrhythmic events. Funding Acknowledgement Type of funding source: None

Background Brugada syndrome (BrS) is a genetic disease associated with increased risk of ventricular fibrillation (VF)/ventricular tachycardia (VT). The VF/VT in BrS occurs more frequently during a night time or at a rest with parasympathetic nerve activation. Some risk factors of VF/VT occurrence in BrS have been elucidated, however, it remains controversial about risk stratification. Salusin-β is an endogenous bioactive peptide that systemically exerts rapid and profound hypotensive and bradycardic activities and parasympathomimetic hemodynamic actions in vivo. Previous reports suggested that salusin-β is suppressed following physiological parasympathetic stimulation and appears to constitute a negative feedback relationship with the parasympathetic nervous system. Purpose We hypothesized that salusin-β is associated with the occurrence of VF/VT in BrS. Methods The study population consisted of 26 BrS patients with newly implantation of implantable cardioverter defibrillator (ICD) during 2003–2008. In all patients, salusin-β was measured in supine position after 20 minute rest. The date of salusin-β sampling was set as the registration point for this study. The VF/VT was defined as any episode of fatal ventricular tachyarrhythmia or any appropriate shock. In accordance with the presence or absence of VF/VT events within 5 years, all patients were divided into VF/VT group (n=6) and non-VF/VT group (n=20).Various clinical parameters were compared between the two groups. For analysis of autonomic nervous function, heart rate variability (HRV) and pupil function were evaluated. Results The mean age was 54±17 years old. There is no differences between the two groups in clinical parameters. In analysis of HRV, the high-frequency component (0.15–0.40 Hz; HF), low frequency component (0.04–0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. LF/HF ratio was significantly lower over 24h in VF/VT groups in comparison with non-VF/VT groups [day-time; 1.8 (1.2–5.6) vs. 5.2 (3.4–8.8), p=0.048, night-time; 1.2 (1.1–1.3) vs. 3.9 (2.5–8.7), p=0.003]. Furthermore, in analysis of pupil function, right/left miosis ratio was higher in VT/VF groups in comparison with non-VT/VF groups [right pupil; 0.39 (0.37–0.59) vs. 0.34 (0.28–0.38), p=0.035, left pupil; 0.43 (0.36–0.50) vs. 0.33 (0.28–0.40), p=0.049]. In plasma total salusin-β levels, the VF/VT groups exhibited significantly lower than non-VF/VT groups (55.2±14.6 vs. 73.2±22.2, p=0.039, Figure). Conclusions Salusin-β was associated with the occurrence of VF/VT in Brugada syndrome. Salusin-β might be useful to identify high-risk patients for the occurrence of VT/VF events in Brugada syndrome. Funding Acknowledgement Type of funding source: None

Complex atrial tachycardias (ATs) after catheter ablation or a MAZE procedure is sometimes difficult to determine the circuits of the tachycardia. A high-density, grid-shapes mapping catheter has been launched, which can be useful for detecting the detail circuits of tachycardias on three-dimensional mapping systems. The signal quality is also important for performing electrophysiological studies (EPSs), such as entrainment mapping, to identify the circuit. This unique mapping catheter has 1 mm electrodes on 2.5 Fr shafts, which improve the signal quality. The high-quality intracardiac electrograms facilitate differentiating small critical potentials, which allows us to perform detailed entrainment mapping in targeted narrow areas. Here, we describe a patient with a perimetral AT with epi-endocardium breakthrough after a MAZE surgery and catheter ablation, which was treated successfully along with detailed entrainment mapping using the HD Grid. This catheter with high-quality signals could be a significant diagnostic tool for a classic EPS as well as for the construction of 3D mapping.

Gastric hypomotility (GH) is a possible complication of catheter ablation (CA) for atrial fibrillation (AF). However, it is unclear which factors are associated with GH. We sought to elucidate the relationship between the CA procedure and GH.The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 119 patients were enrolled and divided into two groups: with or without GH (GH or non-GH groups). To evaluate the association with GH, the clinical backgrounds and procedure characteristics of the radiofrequency CA (RFCA) were compared between the two groups.The median age was 69 years old with 34% of female. GH were observed in 27.7% of patients who underwent RFCA, which was significantly higher than that in the cohort of patients who underwent esophago-gastro-duodenoscopy during the same time period (1.9%: 151 in 8063 patients, p 0.0001). According to the detailed RFCA procedure, additional posterior wall isolation with pulmonary vein isolation (PVI) had a higher prevalence of GH than that with only PVI (54.8% vs. 18.2%; odds ratio 5.46, 95%CI 2.24-13.32, p = 0.0002). After an adjustment using a multivariate logistic analysis, a posterior wall isolation with the PVI was identified as the only independent predictor for GH (odds ratio 5.01, 95%CI 1.94-13.43, p = 0.0009).Additional posterior wall isolation with PVI was associated with gastric hypomotility.

Background: Esophageal leiomyomatosis (EL) is a rare benign tumor defined as a diffuse form of marked hypertrophy in the muscular layer of the esophagus. Relapses have been reported as a result of misdiagnoses of other tumors or achalasia, followed by inappropriate surgical intervention. The endoscopic approach is preferred because of its lesser degree of invasiveness and better cosmesis; however, its effectiveness for treatment of EL is unclear because these tumors are bulkier and more extensive than those in other esophageal diseases. Case presentation: We treated an 11-year-old girl who had been experiencing progressive dysphagia, vomiting, and coughing during sleep since the age of 4 years and was correctly diagnosed with EL using computed tomography and endoscopic ultrasonography. She was successfully treated with total minimally invasive esophagectomy (MIE), combining thoracoscopy and laparoscopy, in the prone position, without any complications or recurrence of symptoms. To our knowledge, this is the first case report of MIE for EL. A review of 84 EL cases (including the present case) revealed a rate of accurate preoperative diagnosis of only 23.8%. Esophagectomy should be employed because the recurrence rate of the non-esophagectomy cases, involving myotomy and tumorectomy, was significantly higher than that of the esophagectomy cases (57.9% vs. 7.7%, p = 0.002). Among 11 relapse cases in the non-esophagectomy cases, esophagectomy was performed in eight. Among the four relapse cases in the esophagectomy group, additional esophagectomy was necessary in three because of insufficient resection of the tumors at the primary esophagectomy. Conclusions: Multimodal imaging contributes to accurate diagnosis and assessment of the extent of the tumors, thus leading to the selection of the appropriate surgical intervention, i.e., radical esophagectomy. Total MIE in the prone position provides excellent exposure of the operative fields; our experience suggests that total MIE is beneficial for EL, as it is for other esophageal tumors. Keywords: Esophageal leiomyomatosis, Minimally invasive esophagectomy, Prone position, Achalasia, Case report, Review of literature

Purpose Fatality resulting from respiratory collapse (RC) during general anesthesia (GA) induction in children with mediastinal tumors has been reported. We explored potentially useful parameters for predicting the risk of RC based on objective imaging results. Methods We retrospectively reviewed the records of 31 patients (median age: 4years; range: 4months–15years) with mediastinal tumors treated between 2000 and 2015. Comparing those with RC under GA induction to those without (RC group vs. non-RC group), we analyzed a variety of factors that might predict respiratory obstruction during GA induction, including our new parameter, the standardized tumor volume (STV), which is adapted from the formula for the volume of an ellipsoid. Results All eight patients in the RC group had large tumors in the anterior mediastinum, including lymphoma, teratoma, and germ cell tumor. The mean STV value of the RC group was significantly larger than that of the non-RC group (3.6±1.4 vs. 1.4±1.0, p =0.006). Using an STV cut-off value of 2.5, the sensitivity and specificity for predicting RC under GA induction were both 0.86, making STV more useful than previously reported risk factors. Conclusion Anterior mediastinal tumors in children can often cause airway obstruction under GA induction. Measuring STV can help predict the respiratory risk during GA among pediatric patients with anterior mediastinal tumors. Level of Evidence III.

Background Right ventricular (RV) pacing causes left ventricular (LV) dysfunction. On the other hand, RV pacing for hypertrophic obstructive cardiomyopathy (HOCM) is an established treatment. LV flow energy loss (EL) is a new hemodynamic index for assessing cardiac function. However, the impact of RV pacing on EL remains unknown. Objective The objective of this study was to investigate the EL by RV pacing on normal LV function and hypertrophic cardiomyopathy (HCM). Methods A total of 28 patients underwent echocardiography for EL assessment under AAI (without RV pacing) and DDD (with all RV pacing) mode. Among them, 16 were sick sinus syndrome (SSS) patients with normal LV function, and 12 were HCM patients. EL was calculated from color Doppler images using a vector flow mapping. Results There were no significant difference in patients' background parameters between the SSS and the HCM groups. In the SSS group, mean systolic EL was significantly increased from AAI to DDD mode (14.9 to 19.2 mW/m, P Change of flow energy loss Conclusion RV pacing increased mean systolic EL in normal LV function, but decreased in HCM with or without LV outflow obstruction. In the patients with HCM, the impact of RV pacing on EL is different compared with normal LV function.

Background Among patients who underwent dual chamber devices (DDD) implantation, new occurrence of atrial fibrillation (AF) is higher compared to general population. However, it is unclear which factors affect new onset AF. Previous studies reported that the prolonged P wave dispersion (PWD) in sinus rhythm could be considered as an index for progression of conduction disturbance as the arrhythmogenic state for AF. In this study, we sought to elucidate the clinical factors including PWD associated with silent atrial high rate episode (AHRE) in the population of DDD. Methods The study population consisted of 101 patients with DDD from 2010 to 2014. All patients were measured PWD at the time of implantation. AHRE was defined as any episode of sustained atrial tachyarrhythmia (>170 bpm). AHREs were evaluated during initial 1 year after the implantation. They were divided into AHRE group (n=34) and non-AHRE group (n=67) and various clinical parameters were compared. Results The mean age was 75±11 years old. The AHRE groups showed higher rate of diagnosis of sick sinus syndrome (p=0.05) and longer PWD (62.6±13.1 versus 38.2±13.9 ms, p ROC curve Conclusion PWD were significant predictor for new appearance of AHRE in patients with DDD.

A 57‐year‐old man was admitted to our hospital due to syncopal attack. He was diagnosed with Brugada syndrome due to which a subcutaneous implantable cardiac defibrillator (S‐ICD) was inserted using the standard technique. Two hours after the implantation, he experienced inappropriate shock while conscious. Device interrogation revealed a contentious baseline shift and frequent oversensing of low‐amplitude signals, which was followed by a shock. Lateral chest X‐ray revealed subcutaneous air surrounding the proximal electrode. Another inappropriate shock could be avoided by changing the sensing vector. The subcutaneous air was completely resolved 7 days after implantation.

Patient initials or identifier number M.S ### Relevant clinical history and physical exam He was diagnosed with paroxysmal atrial fibrillation at the age of 64 and started oral administration of an anticoagulant. However, due to an appearance of stomach discomfort by side effects of a drug

Neuroblastoma (NB) is one of the most common extracranial solid tumors in children and is known for its clinical and biological heterogeneity. The aim of this study is to reveal the functional role of src family kinases in the biological behavior of NB by inhibiting their kinase activities with a specific inhibitor, PP2 (4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine). NB cell lines (SH-SY5Y, IMR32, RT-BM-1, CHP134, NLF, and LA-N-5) were treated with 0.1–10 µM of PP2. Morphological changes, cell growth, and cell death were assessed, as well as all-trans retinoic acid (ATRA)-induced neuronal differentiation and epidermal growth factor (EGF)-induced proliferation. At 24 h after PP2 treatment, NB cell lines showed drastic cell aggregation. PP2 also inhibited cell growth of NB in a dose-dependent manner. Apoptosis was detected in these cells. ATRA-induced neuronal differentiation of RT-BM-1 was not affected by PP2. PP2 reduced the proliferative effect of EGF. EGF-induced rapid activation of Akt, which was not blocked by PP2 treatment, suggesting that the cellular events triggered by PP2 were independent to PI3 kinase/Akt signaling pathway. Our data suggests that src family kinases promote cell survival/proliferation and reduces cell aggregation of NBs. Src family kinase inhibitors may be good candidates for a novel molecular target therapy.

To evaluate the usefulness of multi-detector row computed tomography (MDCT) in the postoperative long-term follow-up of biliary atresia (BA) patients for detection of esophagogastric varices due to portal hypertension and intrahepatic bile duct (IHBD) dilatations. Well-developed esophagogastric varices can cause unexpected life-threatening rupture and contribute to the progression of hepatopulmonary vascular diseases. Dilated IHBDs can trigger cholangitis. After corrective surgery, 29 BA patients (median age 14 years, range 6 months to 27 years) with suspected long-term sequelae underwent 16-slice MDCT. Esophagogastric varices and IHBD dilatations were evaluated using reconstructed images. Detection rates for esophagogastric varices were compared between MDCT and endoscopic findings. Differences in detection rates for IHBD dilatations between MDCT and ultrasonography (US) were also investigated. Detection rates for esophageal varices did not differ significantly between MDCT and endoscopy, while three cases positive only on MDCT, including one with hepatopulmonary syndrome, showed conspicuous peri-esophageal varices deep in the esophageal wall. MDCT showed a significantly higher detection rate than endoscopy (p = 0.03) for gastric fundal varices. MDCT with the maximum intensity projection disclosed IHBD dilatations in 17 postoperative BA cases, 15 out of which had past history of cholangitis, while US detected them in 6 cases (p = 0.003). In addition, MDCT was more advantageous for detecting IHBD dilatations, particularly those located in the posterior lobe. Among postoperative BA patients, compared to endoscopy, MDCT had comparable and superior detection rates for esophageal and gastric fundal varices, respectively. MDCT also precisely demonstrated the location and extent of IHBD dilatations. In long-term follow-up of BA patients, MDCT can help determine follow-up strategies.

Subtilase cytotoxin (SubAB) is an AB 5 cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli . The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum chaperone, BiP, leading to transient inhibition of protein synthesis and cell cycle arrest at G 1 phase. Here we show that SubAB, but not the catalytically inactive mutant SubAB(S272A), induced apoptosis in Vero cells, as detected by DNA fragmentation and annexin V binding. SubAB induced activation of caspase-3, -7, and -8. Caspase-3 appeared earlier than caspase-8, and by use of specific caspase inhibitors, it was determined that caspase-3 may be upstream of caspase-8. A general caspase inhibitor blocked SubAB-induced apoptosis, detected by annexin V binding. SubAB also stimulated cytochrome c release from mitochondria, which was not suppressed by caspase inhibitors. In HeLa cells, Apaf-1 small interfering RNA inhibited caspase-3 activation, suggesting that cytochrome c might form an apoptosome, leading to activation of caspase-3. These data suggested that SubAB induced caspase-dependent apoptosis in Vero cells through mitochondrial membrane damage.

Subtilase cytotoxin (SubAB) is a AB(5) type toxin produced by Shiga-toxigenic Escherichia coli, which exhibits cytotoxicity to Vero cells. SubAB B subunit binds to toxin receptors on the cell surface, whereas the A subunit is a subtilase-like serine protease that specifically cleaves chaperone BiP/Grp78. As noted previously, SubAB caused inhibition of protein synthesis. We now show that the inhibition of protein synthesis was transient and occurred as a result of ER stress induced by cleavage of BiP; it was closely associated with phosphorylation of double-stranded RNA-activated protein kinase-like ER kinase (PERK) and eukaryotic initiation factor-2alpha (eIF2alpha). The phosphorylation of PERK and eIF2alpha was maximal at 30-60 min and then returned to the control level. Protein synthesis after treatment of cells with SubAB was suppressed for 2 h and recovered, followed by induction of stress-inducible C/EBP-homologous protein (CHOP). BiP degradation continued, however, even after protein synthesis recovered. SubAB-treated cells showed cell cycle arrest in G1 phase, which may result from cyclin D1 downregulation caused by both SubAB-induced translational inhibition and continuous prolonged proteasomal degradation.

Some shiga toxin-producing Escherichia coli secrete a novel AB5 cytotoxin, named subtilase cytotoxin (SubAB), which induces vacuole formation in addition to cytotoxicity in susceptible cells. By immunoprecipitation with SubAB from Vero cells, we discovered proteins of 100 kDa, 135 kDa and 155 kDa as potential candidates for its receptor. These proteins were N-glycosylated in their extracellular domains, a modification that was necessary for interaction with SubAB. Biotinylated receptors were partially purified by Datura stramonium agglutinin affinity chromatography and avidin-agarose and analysed by TOF mass spectroscopy. The peptide sequences of p135 were identical to beta1 integrin, and its identification was confirmed with anti-integrin beta1 antibody. The p155 protein was identified as alpha2 integrin using anti-integrin alpha2 antibody. In addition, treatment of Vero cells with beta1 integrin RNAi before exposure to SubAB prevented vacuolating activity. These results suggested that SubAB recognizes alpha2beta1 integrin as a functional receptor; this first interaction may be an important key step leading to the SubAB-induced morphological changes in Vero cells.

Background: A mass-screened neuroblastoma (MSN) shows low-grade malignancy. Although the tumor is small, open laparotomy requires a large incision. Purpose: Extirpation by retroperitoneoscopy (ER) was performed in children with MSN to reduce the surgical stress. Methods: The indications for ER were (1) MSN originating from the adrenal gland and (2) a tumor size of less than 4 cm. Between January 2000 and June 2002, 6 children (mean age: 8.5 ± 0.6 months) underwent ER. Results: All children successfully underwent ER and no conversion of laparoscopy to open surgery was required. The only complication in one patient was a peritoneal tear. Oral intake was possible in all children the day after the operation. No port site metastasis or local recurrence was observed during follow-up (15 to 29 months). Conclusions: Adrenal MSN less than 4 cm were successfully extirpated by ER. This method has the advantage of allowing patients an early return to eating and has no risk of postoperative ileus. ER is an available surgical technique for children with MSN less than 4 cm.

A rare case of gastric duplication of childhood is reported. A 1-month-old boy underwent pyloromyotomy for infantile hypertrophic pyloric stenosis. At laparotomy, a protruding lesion was identified in the anterior wall of the pylorus. The pylorus was hypertrophic as indicated preoperatively, and a normal pyloromyotomy was performed. Wedge biopsy of the protruding lesion revealed an intestinal structure, and gastric duplication was diagnosed. The child remained asymptomatic thereafter, but considering the risk of the duplication becoming symptomatic, a second laparotomy was performed at 1 year of age. The duplication cyst shared part of the wall with the pylorus, and the cyst was removed by cystectomy, leaving the pyloric muscle intact. The cyst was found to be communicating with the pancreatic duct. The child is doing well without any symptoms as of 18 months after second laparotomy. To the best of our knowledge, this is the youngest case of gastroduodenal duplication with pancreatic duct communication yet reported.

Background Standard choledochal cyst (CC) operations involve dilated extrahepatic bile duct excision followed by biloenterostomy. However, biliary variants and associated intrahepatic bile duct (IHBD) stenoses or dilatations triggering postoperative sequelae require additional procedures. The usefulness of preoperative 3-dimensional magnetic resonance cholangiopancreatography (3D MRCP) and virtual cholangioscopy (VES) for observing biliary morphology and pancreaticobiliary maljunction (PBM) was evaluated. Methods In 16 pediatric CC patients (age range, 4 months to 9 years; median, 3 years), visualization of PBM and aberrant bile duct anatomy and IHBD morphology at the hepatic hilum (HH), umbilical portion (UP), and posterior branch (POST) were compared between 3D-MRCP and intraoperative cholangiography (IOC). VES and intraoperative cholangioscopy (IOS) findings were compared. Results HH, UP, and POST visualization rates were 100%, 94%, and 94%, respectively, by 3D-MRCP, and 100%, 69%, and 69%, respectively, by IOC. IHBD stenosis detection rates at each region were 38%, 13%, and 13%, respectively, by 3D-MRCP, and 25%, 0%, and 9%, respectively, by IOC. IHBD dilatation detection rates at each part were 75%, 47%, and 60%, respectively, by 3D-MRCP, and 88%, 82%, and 91%, respectively, by IOC. PBM was confirmed in 56% and 93% of cases on 3D-MRCP and IOC, respectively. Both 3D-MRCP and IOC showed biliary variants in 5 cases (31%). VES showed membranous strictures at HH, UP, and POST in 6, 2, and 2 cases, respectively, whereas IOS did so at HH in 4 cases and POST in 2. Conclusion Preoperative 3D-MRCP and VES accurately depict biliary morphology, allowing concrete operative planning in pediatric CC patients, complementing IOC and IOS.