Factors predicting the progression from paroxysmal to persistent atrial fibrillation despite an index catheter ablation.

INTRODUCTION: Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF. METHODS: This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated. RESULTS: The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow-up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non-pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non-PV triggers, and a history of thyroid disease independently predicted AF progression. CONCLUSION: The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non-PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.

Application of Ensite™ LiveView function for identification of scar-related ventricular tachycardia isthmus.

INTRODUCTION: Dynamic display of real-time wavefront activation pattern may facilitate the recognition of reentrant circuits, particularly the diastolic path of ventricular tachycardia (VT). OBJECTIVE: We aimed to evaluate the feasibility of LiveView Dynamic Display for mapping the critical isthmus of scar-related reentrant VT. METHODS: Patients with mappable scar-related reentrant VT were selected. The characteristics of the underlying substrates and VT circuits were assessed using HD grid multielectrode catheter. The VT isthmuses were identified based on the activation map, entrainment, and ablation results. The accuracy of the LiveView findings in detecting potential VT isthmus was assessed. RESULTS: We studied 18 scar-related reentrant VTs in 10 patients (median age: 59.5 years, 100% male) including 6 and 4 patients with ischemic and nonischemic cardiomyopathy, respectively. The median VT cycle length was 426 ms (interquartile range: 386-466 ms). Among 590 regional mapping displays, 92.0% of the VT isthmus sites were identified by LiveView Dynamic Display. The accuracy of LiveView for isthmus identification was 84%, with positive and negative predictive values of 54.8% and 97.8%, respectively. The area with abnormal electrograms was negatively correlated with the accuracy of LiveView Dynamic Display (r = -.506, p = .027). The median time interval to identify a VT isthmus using LiveView was significantly shorter than that using conventional activation maps (50.5 [29.8-120] vs. 219 [157.5-400.8] s, p = .015). CONCLUSION: This study demonstrated the feasibility of LiveView Dynamic Display in identifying the critical isthmus of scar-related VT with modest accuracy.

Skin sympathetic nerve activity in different ablation settings for atrial fibrillation.

BACKGROUND: Modifying the autonomic system after catheter ablation may prevent the recurrence of atrial fibrillation (AF). Evaluation of skin sympathetic nerve activity (SKNA) is a noninvasive method for the assessment of sympathetic activity. However, there are few studies on the effects of different energy settings on SKNA. OBJECTIVE: To investigate the changes in SKNA in different energy settings and their relationship to AF ablation outcomes. METHODS: Seventy-two patients with paroxysmal and persistent AF were enrolled. Forty-three patients received AF ablation with the conventional (ConV) energy setting (low power for long duration), and 29 patients using a high-power, short-duration (HPSD) strategy. The SKNA was acquired from the right arm 1 day before and after the radiofrequency ablation. We analyzed the SKNA and ablation outcomes in the different energy settings. RESULTS: Both groups had a similar baseline average SKNA (aSKNA). We found that the median aSKNA increased significantly from 446.82 µV to 805.93 µV (p = 0.003) in the ConV group but not in the HPSD group. In the ConV group, patients without AF recurrence had higher aSKNA values. However, the 1-year AF recurrence rate remained similar between both groups (35 % vs. 28 %, p = 0.52). CONCLUSION: The post-ablation aSKNA levels increased significantly in the ConV group but did not change significantly in the HPSD group, which may reflect different neuromodulatory effects. However, the one-year AF recurrence rates were similar for both groups. These results demonstrate that the HPSD strategy has durable lesion creation but less lesion depth, which may reduce collateral damage.

Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.

BACKGROUND: The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome. METHODS: Forty-five paroxysmal AF patients (30 males, 57.8±8.7 years old) who underwent pulmonary vein isolation were enrolled. Isochronal late activation mapping was retrospectively constructed with 2 different windows of interest: from onset of P wave to onset of QRS wave on surface electrocardiography (W1) and 74 ms tracking back from the end of P wave (W2). Deceleration zone was defined as regions with 3 isochrones (DZa) or ≥4 isochrones (DZb) within a 1 cm radius on the isochronal late activation mapping, and the estimated conduction velocity (ECV) are 0.27 m/s and <0.20 m/s for DZa and DZb, respectively in W2. The distribution of deceleration zone was compared with the location of low-voltage zone (bipolar voltage ≤0.5 mV). Any recurrence of atrial arrhythmias was defined as the primary end point during follow ups after a 3-month blanking period. RESULTS: Pulmonary vein isolation was performed in all patients, and there were 2 patients (4.4%) received additional extrapulmonary vein ablation. After a mean follow-up of 12.7±4.5 months, recurrence of AF occurred in 14 patients (31.1%). Patients with the presence of DZb in W2 had higher AF recurrence (Kaplan-Meier event rate estimates: HR, 9.41 [95% CI, 2.61-33.90]; log-rank P<0.0001). There were 52.6% of the DZb locations in W2 comparable to the distributions of low-voltage zone and 47.4% DZb were distributed in the area without low-voltage zone. CONCLUSIONS: Deceleration zone detected by isochronal late activation mapping represents a critical AF substrate, it accurately predicts the AF recurrence following ablation in patients with paroxysmal AF.

Post-ablation augmentation of skin sympathetic nerve activity predicts a poor outcome of idiopathic ventricular arrhythmias.

BACKGROUND: The neuromodulation effect after ventricular arrhythmia (VA) ablation is unclear. The study aimed to investigate skin sympathetic nerve activity (SKNA) changes in patients receiving catheter ablations for idiopathic VA. METHODS: Of 43 patients with drug-refractory symptomatic VA receiving ablation, SKNA was continuously recorded for 10 min during resting from electrocardiogram lead I configuration and bipolar electrodes on the right arm 1 day before and 1 day after ablation. RESULTS: Twenty-two patients with acute procedure success and no recurrence during follow-ups were classified as sustained success group (group 1). Other 21 patients were classified as failed ablation group (group 2). Baseline SKNA showed no significant difference between the two groups. Post-ablation SKNA in group 2 was significantly higher than in group 1. In patients with ablation involved right ventricular outflow tract (RVOT), the post-ablation SKNA was also significantly higher in group 2. In contrast, there was no difference in post-ablation SKNA between groups in patients receiving non-RVOT ablation. CONCLUSION: The neuromodulation response after RVOT ablation may correspond to the sympathetic nerve distribution at RVOT. Augmentation of sympathetic activity after VA ablation indicates an unsuccessful VA suppression, especially in patients receiving ablation of RVOT VA.

Reversal of multidrug resistance by Fissistigma latifolium-derived chalconoid 2-hydroxy-4,5,6-trimethoxydihydrochalcone in cancer cell lines overexpressing human P-glycoprotein.

Cancer treatment is an evolving field with various challenges to clinical practice. One unresolved problem in this field is multidrug resistance (MDR) mediated by ABC efflux transporters, particularly P-glycoprotein (P-gp). In this study, by prescreening compounds, we identified the potential of a dihydrochalcone compound, 2-hydroxy-4,5,6-trimethoxydihydrochalcone, for P-gp inhibition. Therefore, we investigated its ability to inhibit P-gp and reverse P-gp-mediated MDR, as well as the underlying mechanisms. The P-gp-inhibitory effects of 2-hydroxy-4,5,6-trimethoxydihydrochalcone were investigated as follows. A P-gp efflux assay and an ATPase assay were used to understand the modulatory mechanisms in the drug-binding and ATP-binding areas, respectively. Prominent reversal effects observed in MDR cancer cell lines; thus, reversal, cytotoxicity, cell cycle, apoptosis, and reactive oxygen species assays were conducted to investigate the underlying mechanism. The results indicated that 2-hydroxy-4,5,6-trimethoxydihydrochalcone functionally inhibited P-gp in a noncompetitive manner, and this inhibition was unrelated to expression. In addition, 2-hydroxy-4,5,6-trimethoxydihydrochalcone served as an ATPase stimulator but not as a P-gp substrate. Moreover, a low binding energy of - 6.85 kcal/mol and one hydrogen bond were obtained, indicating that 2-hydroxy-4,5,6-trimethoxydihydrochalcone has a high affinity for P-gp. P-gp-mediated MDR was reversed by 31.6 µM 2-hydroxy-4,5,6-trimethoxydihydrochalcone in combination with paclitaxel, with a reversal fold value of 379.42. In conclusion, this study provides evidence of the ability of 2-hydroxy-4,5,6-trimethoxydihydrochalcone to inhibit P-gp and reverse MDR.

Electrophysiological characteristics of epicardial breakthrough during catheter ablation of perimitral atrial flutter.

Introduction: Unsuccessful endocardial ablation for perimitral atrial flutter (AFL) could be attributed by the epicardial bridging. Objective: This study aimed to investigate the electrophysiological characteristics of epicardial breakthrough during catheter ablation of perimitral AFL. Materials and methods: This retrospective study recruited 40 patients who received successful catheter ablation of perimitral AFL from January 2016 to June 2021. The patients were divided into two groups: group 1 (n = 18) successful endocardial ablation, and group 2 (n = 22) successful epicardial ablation following unsuccessful endocardial ablation owing to incomplete mitral block or unachievable termination AFL. The local electrogram (EGM) interval of coronary sinus (CS) duration perimitral AFL was measured before catheter ablation. Results: There was no significant difference in the baseline characteristics between the two groups. In group 2, 60% of successful epicardial ablation was performed in intra-CS ablation and 40% in VOM ethanol infusion. Group 2 patients had a longer EGM interval of distal CS than that in group 1 (CS1-2: 64.2 17.5 vs. 42.4 0.09 ms, P = 0.008, CS3-4: 57.13 19.4 vs. 43.8 7.5 ms; P = 0.001). The conduction velocity at successful site was slower in group 2 compared to group 1 (0.18 0.05 vs. 0.75 0.19 m/s, P = 0.040). In the multivariate analysis, distal EGM interval (CS1-2) was identified as independent predictor of the need of epicardial ablation with the optimal cutoff of 49 ms. Conclusion: Longer EGM interval in distal CS during perimitral AFL was observed in perimitral AFL patients with epicardial breakthrough following endocardial-failed ablation, which may be associated with the need of epicardial ablation.

Skin sympathetic nerve activity and ventricular arrhythmias in acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is major cause of ventricular arrhythmias (VAs) and sudden death. neuECG is a noninvasive method to simultaneously record skin sympathetic nerve activity (SKNA) and electrocardiogram. OBJECTIVE: The purpose of this study was to test the hypotheses that (1) ACS increases average SKNA (aSKNA), (2) the magnitude of aSKNA elevation is associated with VAs during ACS, and (3) there is a gender difference in aSKNA between patients without and with ACS. METHODS: We prospectively studied 128 ACS and 165 control participants. The neuECG was recorded with electrodes at Lead I configuration at baseline, during mental math stress, and during recovery (5 minutes for each phase). All recordings were done in the morning. RESULTS: In the control group, women have higher aSKNA than do men at baseline (0.82 ± 0.25 µV vs 0.73 ± 0.20 µV; P = .009) but not during mental stress (1.21 ± 0.36 µV vs 1.16 ± 0.36 µV; P = .394), suggesting women had lower sympathetic reserve. In comparison, ACS is associated with equally elevated aSKNA in women vs men at baseline (1.14 ± 0.33 µV vs 1.04 ± 0.35 µV; P = .531), during mental stress (1.46 ± 0.32 µV vs 1.33 ± 0.37 µV; P = .113), and during recovery (1.30 ± 0.33 µV vs 1.11 ± 0.30 µV; P = .075). After adjusting for age and gender, the adjusted odds ratio for VAs including ventricular tachycardia and ventricular fibrillation is 1.23 (95% confidence interval 1.05-1.44) for each 0.1 µV aSKNA elevation. aSKNA is positively correlated with plasma norepinephrine level. CONCLUSION: ACS is associated with elevated aSKNA, and the magnitude of aSKNA elevation is associated with the occurrence of VAs. Women have higher aSKNA and lower SKNA reserve than do men among controls but not among patients with ACS.

Application of dynamic display technology to identify gaps after pulmonary vein isolation in catheter ablation of atrial fibrillation.

BACKGROUND: The identification of post pulmonary vein isolation (PVI) gaps by activation and voltage maps is time-consuming. This study aimed to investigate the characteristics, efficiency and accuracy of LiveView dynamic display module (EnSite™ Dynamic Display; Abbott, Abbott Park, IL, USA) in unmasking post PVI gaps and conduction block line. METHOD: Twenty four patients with paroxysmal atrial fibrillation (PAF) who failed to achieve first-pass PVI or with recurrent PAF were enrolled. Ninety-six pulmonary veins (PVs) were evaluated, and gaps were identified in 25 (26.0%) PVs. The gap location was confirmed by activation and propagation maps; 110 frames on gaps and 118 frames on block lines were analyzed by using LiveView module. We defined isochronal crowding in the local activation time (LAT) mode as three colors between two adjacent electrodes. Each frame was classified as with or without isochronal crowding in LAT mode and one/continuous color or isochronal discontinuity in reentrant mode. The gray color inside the PVs was considered to represent conduction block. RESULT: The isochronal crowding could be found on both gap and block line in LAT mode, whereas isochronal discontinuity only presented on the block line in reentrant mode. The sensitivity and specificity of isochronal discontinuity or gray color in reentrant mode to identify block line were 61.0% and 100%, respectively. The sensitivity and specificity of isochronal crowding or gray color in LAT mode to identify block line were 71.2% and 71.8%, respectively. CONCLUSION: Reentrant mode in LiveView module is very specific in identifying block lines. We proposed an efficient, practical algorithm to differentiate the block line from PV gaps.

Low voltage zones detected by omnipolar Vmax map accurately identifies the potential atrial substrate and predicts the AF ablation outcome after PV isolation.

INTRODUCTION: The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation (PVI). However, changes of wavefront and bipole directions may cause different electrogram characteristics. We aimed to investigate whether using omnipolar maximum voltage (Vmax) map derived from high density (HD) Grid mapping catheter could assess LVZ and AF ablation outcome accurately. METHODS: Fifty paroxysmal AF patients (27 males, 57.8 ± 9.5 years old) who underwent 3D mapping guided PVI were enrolled. Left atrial voltage mapping during sinus rhythm before ablation was performed. The significant LVZ (<0.5 mV with area > 5 cm2) were defined as sites by omnipolar Vmax, bipolar HD wave map, conventional bipolar electrograms acquired from electrode pairs along to and across to the catheter shaft. The primary end point was the first documented recurrence of any AF during follow-ups. RESULTS: PVI was performed in all patients, and there were 2 patients (4%) who also received additional non-PV triggers ablation. After a follow-up of 11.4 ± 5.4 months, recurrence of AF occurred in 12 patients (24%). The presence of a significant LVZ was less detected by omnipolar Vmax map, compared to HD wave map (24.0% vs. 58.0%, p = 0.001). LVZ detected by omnipolar Vmax map independently predicted the AF recurrence (odds ratio 16.91; 95% CI, 3.17-90.10; p = 0.001). CONCLUSION: LVZ detected by omnipolar Vmax map accurately predicts the AF recurrence following ablation in paroxysmal AF, compared to conventional bipolar and HD wave maps, suggesting the omnipolar Vmax map can precisely define the atrial substrate property.

Alteration of Skin Sympathetic Nerve Activity after Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation.

Autonomic system plays a pivotal role in the pathogenesis of paroxysmal atrial fibrillation (AF). Skin sympathetic nerve activity (SKNA) is a noninvasive tool for assessing sympathetic tone. However, data on changes in SKNA after ablation are limited. Here, we retrospectively enrolled 37 patients with symptomatic drug-refractory paroxysmal AF who underwent pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) or cryoablation (CBA). SKNA was measured from the chest and right arm 1 day prior to ablation, as well as 1 day and 3 months after ablation. One day after ablation, the SKNA-Arm increased from 517.1 µV (first and third quartiles, 396.0 and 728.0, respectively) to 1226.2 µV (first and third quartiles, 555.2 and 2281.0), with an increase of 179.8% (125% and 376.0%) (p < 0.001); the SKNA-Chest increased from 538.2 µV (first and third quartiles, 432.9 and 663.9) to 640.0 µV (first and third quartiles, 474.2 and 925.6), with an increase of 108.3% (95.6% and 167.9%) (p = 0.004), respectively. In those without recurrence, there was a significant increase in SKNA 1 day after ablation as compared with those before ablation. Twelve patients received SKNA measurement 3 months after ablation; both SKNA-Arm (p = 0.31) and SKNA-Chest (p = 0.27) were similar to those before ablation, respectively. Among patients with symptomatic drug-refractory paroxysmal AF receiving PVI, increased SKNA was observed 1 day after ablation and returned to the baseline 3 months after ablation. Elevation of SKNA was associated with lower early and late recurrences following ablation.

High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope.

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the "Italian protocol"), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, µV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The "SKNA-SDNN index" was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p < 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Resolution of left ventricular thrombus by edoxaban after failed treatment with warfarin overdose: A case report.

RATIONALE: Although novel oral-anticoagulants are widely used in patients with atrial fibrillation (AF) for stroke prevention, there was only limited evidence for their use in left ventricular (LV) thrombus. PATIENT CONCERNS: A 41-year-old man who presented with acute onset of right-hand clumsiness and aphasia even under high international normalized ratio (INR: 7.64) from warfarin use. He was previously treated with warfarin for the LV thrombus and non-valvular AF. Brain magnetic resonance imaging (MRI) showed multiple acute infarction in the cortex of the bilateral frontal lobes, left parietal lobe, and bilateral central semiovale, which highly suggested embolic stroke. DIAGNOSIS: The repeated transthoracic echocardiogram still revealed LV thrombus (1.27 × 0.90 cm), which failed to respond to warfarin therapy. INTERVENTIONS: Due to acute infarctions occurred under supratherapeutic range of INR, we switched warfarin to edoxaban (dose: 60 mg/day) after INR decreased to less than 2. OUTCOMES: The thrombus disappeared after receiving edoxaban for 23 days, and no more recurrent stroke was noted for more than 6 months. LESSONS: This is the first case demonstrates that while facing ineffective treatment of warfarin for LV thrombus, edoxaban could be safely and effectively used under this situation.