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Background Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity. Objective The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF. Methods Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin. Results Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P Conclusion PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.

Symptomatic intracerebral hemorrhages (ICHs) are a rare complication after atrial fibrillation (AF) catheter ablation, while the incidence of asymptomatic ICHs detected by magnetic resonance (MR) imaging remains unclear. This study aimed to investigate the incidence, characteristics, and predictors of new-onset ICHs on MR imaging after AF ablation. We retrospectively studied 1257 consecutive AF ablation procedures in 1201 patients who underwent MR imaging on the day after the procedure. Repeat MR imaging within 3 months post-ablation was available in 352 procedures. Old ICHs on the initial MR imaging were observed in 28 procedures (2.2%). Post-ablation new ICHs were observed in 14 procedures (4.0%), including one symptomatic (0.3%) and 13 (3.7%) asymptomatic ICHs. One patient had a new ICH on the initial MR imaging, while the remaining 13 had such on the repeat MR imaging. A univariate analysis revealed that a previous ischemic stroke or transient ischemic attack (TIA) and the CHA2DS2-VASc score were positive predictors of new ICHs (odds ratios, 5.502 and 1.435; P = 0.004 and 0.044). The lesion diameter did not significantly differ between the old and new ICHs (median, 6.1 mm vs. 8.0 mm, P = 0.281), while the predominant location differed (lobar areas, 22.6% vs. 53.3%; cerebellum, 22.6% vs. 20.0%; others, 54.8% vs. 26.7%; P = 0.026). A few asymptomatic ICHs may occur after AF ablation. Most of the post-ablation new ICHs occurred a few days or later after the procedure. A previous ischemic stroke/TIA and the CHA2DS2-VASc score may be risk factors for post-ablation ICHs.

Introduction: Ultra-high-density mapping for ventricular tachycardia (VT) is increasingly used. However, manual annotation of local abnormal ventricular activities (LAVAs) is challenging in this setting. Therefore, we assessed the accuracy of the automatic annotation of LAVAs with the Lumipoint algorithm of the Rhythmia system (Boston Scientific). Methods and Results: One hundred consecutive patients undergoing catheter ablation of scar-related VT were studied. Areas with LAVAs and ablation sites were manually annotated during the procedure and compared with automatically annotated areas using the Lumipoint features for detecting late potentials (LP), fragmented potentials (FP), and double potentials (DP). The accuracy of each automatic annotation feature was assessed by re-evaluating local potentials within automatically annotated areas. Automatically annotated areas matched with manually annotated areas in 64 cases (64%), identified an area with LAVAs missed during manual annotation in 15 cases (15%), and did not highlight areas identified with manual annotation in 18 cases (18%). Automatic FP annotation accurately detected LAVAs regardless of the cardiac rhythm or scar location; automatic LP annotation accurately detected LAVAs in sinus rhythm, but was affected by the scar location during ventricular pacing; automatic DP annotation was not affected by the mapping rhythm, but its accuracy was suboptimal when the scar was located on the right ventricle or epicardium. Conclusion: The Lumipoint algorithm was as/more accurate than manual annotation in 79% of patients. FP annotation detected LAVAs most accurately regardless of mapping rhythm and scar location. The accuracy of LP and DP annotations varied depending on mapping rhythm or scar location.

Background Localized staining due to venule injury is attributable to ethanol infusion into the vein of Marshall (Et-VOM). Objective The purpose of this study was to investigate adverse outcomes of localized staining during Et-VOM in patients undergoing ablation for atrial fibrillation. Methods Two hundred four patients (age 64 ± 10 years; 153 male) were sorted based on the aspect of localized staining. Staining of atrial myocardium that spread uniformly along the VOM vascular tree following selective VOM venography was considered normal, in contrast to predominantly localized staining that spread concentrically from a focal point due to vascular injury. Outcomes between the 2 groups were compared. Results Localized staining was observed in 27% of patients. No patients developed clinically significant pericardial effusions during Et-VOM; however, 7 patients developed pericardial effusions on the first postprocedural day (3.6% in patients with vs 3.4% in patients without localized staining). No significant difference was found in achievement of acute mitral isthmus (MI) block (96% vs 98%) and size of the endocardial low-voltage area (8.5 ± 4.1 cm2 vs 9.3 ± 5.3 cm2) in patients with and without localized staining, respectively. Long-term follow-up was not impacted by localized staining. Freedom from recurrent atrial tachyarrhythmias (66% vs 76%) and durability of MI block (57% vs 54%) were not significantly different with and without localized staining. There were no cases of rehospitalization for pericarditis, chronic pericardial effusion, or heart failure. Conclusion In our study, localized staining was frequent but was not associated with clinically relevant impact or disadvantages.

Aims An incomplete understanding of the mechanism of atrial tachycardia (AT) is a major determinant of ablation failure. We systematically evaluated the mechanisms of AT using ultra-high-resolution mapping in a large cohort of patients. Methods and results We included 107 consecutive patients (mean age: 65.7 ± 9.2 years, males: 81 patients) with documented endocardial gap-related AT after left atrial ablation for persistent atrial fibrillation (AF). We analysed the mechanism of 134 AT (94 macro-re-entries and 40 localized re-entries) using high-resolution activation mapping in combination with high-density voltage and entrainment mapping. Voltage in the conducting channels may be extremely low, even Conclusion High-resolution activation mapping in combination with high-density voltage and entrainment mapping is the ideal strategy to delineate the critical part of the circuit in endocardial gap-related re-entrant AT after AF ablation.

Background Data on the optimal location of the ECG leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with Torsades de Pointes (TdP) are lacking. Methods We systematically reviewed the literature for ECGs of patients with diLQTS and subsequent TdP. We assessed T-wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion. Results Of 84 patients, 61.9% were female and mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (standard deviation) 671 (102) vs 655 (97) ms, p=0.02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were non-interpretable: 10 (11.9%) due to too flat T-waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were non-interpretable in 9 (10.7%) patients: 6 (7.1%) due to frequent, early PVCs, 1 (1.2%) due to insufficient ECG quality, 2 (2.4%) due to missing chest leads but none due to too flat T-waves. The most common T-wave morphologies in the limb leads were flat (51.0%), broad (14.3%) and late peaking (12.6%) T-waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%) and biphasic (15.2%) T-waves. Conclusions Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG. This article is protected by copyright. All rights reserved.

Aims We hypothesized that an epicardial approach using ethanol infusion in the vein of Marshall (EIVOM) may improve the result of ablation for perimitral flutter (PMF). Methods and results We studied 103 consecutive patients with PMF undergoing high-resolution mapping. The first 71 were treated with radiofrequency (RF) ablation alone (RF-group), and the next 32 underwent EIVOM followed by RF on the endocardial and epicardial mitral isthmus (EIVOM/RF-group). Contact force was not measured during ablation. Acute and 1-year outcomes were compared. Flutter termination rates were similar between the RF-group (63/71, 88.7%) and EIVOM/RF-group (31/32, 96.8%, P = 0.27). Atrial tachycardia (AT) terminated with EIVOM alone in 22/32 (68.6%) in the EIVOM/RF-group. Bidirectional block of mitral isthmus was always achieved in the EIVOM/RF-group, but significantly less frequently achieved in the RF-group (62/71, 87.3%; P = 0.05). Median RF duration for AT termination/conversion was shorter [0 (0–6) s in the EIVOM/RF-group than 312 (55–610) s in the RF-group, P Conclusion Ethanol infusion in the vein of Marshall may reduce RF duration required for PMF termination as well as for mitral isthmus block without severe complications, and the mid-term outcome may be improved by this approach.

BACKGROUND Abnormal atrial potential (AAP) during sinus rhythm may be a critical ablation target for atrial fibrillation. However, the assessment of local electrograms throughout the left atrium is difficult. Thus, we sought to investigate the effectiveness of Ripple map guided AAP ablation. METHODS AND RESULTS AAP areas were determined by Ripple mapping on the CARTO system in 35 patients (Ripple group) by marking the area where small deflections persisted after the first deflection wavefront had passed. Following pulmonary vein isolation, AAP areas were ablated. If AAP areas were located on the left atrial posterior wall, the posterior wall was isolated. The outcome of this approach was compared with that of 66 patients who underwent an empirical linear ablation approach (control group). There were no differences in patient characteristics between the groups. The total radiofrequency application time and procedure time were shorter in the Ripple group than in the control group (radiofrequency application time, 48 ± 14 minutes vs 61 ± 13 minutes, P

Background No study to date has used high-density mapping to investigate the relationship between prior radiofrequency (RF) lesions for persistent atrial fibrillation (PsAF) ablation and subsequent atrial tachycardias (ATs). Methods From 41 consecutive patients who underwent AT ablation at a second procedure using an ultrahigh-density mapping system, 22 patients (38 ATs) were included as they also had complete maps with a multipolar catheter and three-dimensional (3D) mapping system at the time of the first PsAF ablation procedure. We, therefore, compared voltage maps from the first AF ablation procedure to those from the subsequent AT ablation procedure, as well as the lesion sets used for AF ablation vs the activation patterns in AT during the second procedure. Results In the 38 ATs, 211 of 285 analyzed atrial areas displayed low voltage area (LVA) (74%). Eighteen percent (38/211) existed before the index ablation for AF while 82% (173/211) were newly identified as LVA during the second procedure. Ninety-nine percent (172/173) of the newly developed LVA colocalized with RF lesions delivered for PsAF. Of the 38 ATs, 89.5% (34/38) AT circuits were associated with newly developed LVA due to RF lesions whilst 10.5% (4/38) AT circuits were associated with pre-existing LVA observed at the index procedure. No AT circuit was completely independent from index RF lesions in this series. Conclusions Analysis of detailed 3D electroanatomical mapping demonstrates that most ATs after PsAF ablation are involving LVAs due to index RF lesions.

We describe varying physiologic ventricular resynchronization owing to differences in atrial rhythm in a patient with the right-sided accessory pathway and pre-existing right bundle branch block.

Background The impact of the left atrial low‐voltage area (LVA) on the cardiac function improvement following ablation for atrial fibrillation (AF) is unclear. Methods In 49 patients with paroxysmal AF who underwent ablation, the left ventricular stroke volume index (SVI) was repeatedly measured using an impedance cardiography until 6 months after ablation. We defined the cardiac function improvement as a 20% increase in the SVI. The LVA (the area with the voltage amplitude of

Background The impact of left atrial posterior wall isolation (LAPWI) on the complex fractionated atrial electrogram (CFAE) is unknown. Methods CFAE mapping was performed before and after LAPWI in 46 patients with persistent atrial fibrillation (AF). Results LAPWI decreased both the variable (fractionated index ≤ 120 ms; from 60 ± 4 cm2 to 50 ± 4 cm2, P

P-wave parameters representing atrial conduction heterogeneity are associated with recurrence of atrial fibrillation (AF) after catheter ablation. However, intra- and inter-observer variabilities are unavoidable during manual measurement of P-wave parameters.The study included 201 patients with paroxysmal AF who underwent catheter ablation. P-wave duration (PWD) was measured using a computerized automated measurement system with a surface 12-lead electrocardiogram. The coefficient of variation of PWD (CV-PWD) across the 12 electrocardiographic leads was determined as an index of atrial conduction heterogeneity.AF did not recur in 157 (78%) patients during a 12-month follow-up period. CV-PWD assessed before catheter ablation was not different between the AF-recurrent and AF-free groups (0.069 ± 0.023 vs. 0.069 ± 0.023, P = 0.090). However, CV-PWD measured after catheter ablation was significantly larger in the AF-recurrent group than in the AF-free group (0.090 ± 0.037 vs. 0.073 ± 0.024, P 0.001). In receiver operating curve analysis, CV-PWD assessed after catheter ablation achieved an area under the curve of 0.702; the sensitivity, specificity, and positive and negative predictive values were 68%, 69%, 38%, and 88%, respectively, for the cut-off value of 0.080. During the follow-up period, AF freedom rates of high CV-PWD patients (CV-PWD ≥ 0.080) and low CV-PWD patients (CV-PWD 0.080) were 65% and 88%, respectively.CV-PWD determined using an automated measurement system was associated with AF recurrence after catheter ablation in patients with paroxysmal AF.

This study sought to introduce a computed tomography (CT) protocol for optimal planning of vein of Marshall (VOM) catheterization.Ethanol infusion into the VOM (Et-VOM) is increasingly used in atrial fibrillation ablation.Preprocedural CT was performed with either a conventional (conv-CT; n = 132) or an optimized CT protocol (VOM-CT; n = 126) designed for obtaining on a single image both left atrial and coronary sinus (CS) enhancement. The detection rate and anatomical features of the CT-derived VOM were analyzed and the utility of VOM-CT protocol was assessed by comparing the procedural data.VOM was detected in 35% in conv-CT versus 63% in VOM-CT (P 0.001). The VOM-CT protocol did not impair the assessment of left atrial anatomy and appendage patency. In VOM-CT, the detection of the VOM was related to body mass index and width of epicardial space on posterior wall. Mean distance between CS ostium and VOM was 36 ± 7 mm. Mean VOM diameter was 1.6 ± 0.3 mm. On the CS circumference, the VOM emerged superiorly in 68% and postero-superiorly in 32%. Ethanol infusion into the VOM was attempted in 165 patients (77 conv-CT, 70 VOM-CT, and 18 without-CT). After registration in CARTO, the VOM segmented on CT matched its location on venography in all cases. As compared with conv-CT and without-CT, procedures guided by VOM-CT showed significantly shorter radiation time, shorter procedure time, lower amount of the contrast medium, and fewer contrast injections to obtain VOM catheterization.The proposed CT protocol allows for improved visualization of the VOM, translating into easier VOM catheterization.

Little is known about persistent atrial fibrillation (AF) ablation in patients with cardiac laminopathy (CLMNA).We aimed to characterize atrial electrophysiological properties and to assess the long-term outcomes of persistent AF ablation in patients with CLMNA.All patients with CLMNA referred in our center for persistent AF ablation were retrospectively included. Left atrial (LA) volume, left atrial appendage (LAA) cycle length, interatrial conduction delay, and LA voltage amplitude were analyzed during the ablation procedure. Sinus rhythm maintenance and LA contractile function were assessed during long-term follow-up.From 2011 to 2020, 8 patients were included. The mean age was 47 ± 14 years, and 3 patients (38%) were women. The LA volume was 205.8 ± 43.7 mL; the LAA AF cycle length was 250.7 ± 85.6 ms; and the interatrial conduction delay was 296.5 ± 110.1 ms. Large low-voltage areas (50% of the LA surface;0.5 mV electrogram) were recorded in all 8 patients. Two patients had inadvertent LAA disconnection during ablation. All A waves recorded by pulsed Doppler in sinus rhythm were30 cm/s before and after AF ablation. Early arrhythmia recurrence was recorded in 7 patients (87%) (time to recurrence 4 ± 4 months; 1.5 procedures per patient). After a mean follow-up of 4.4 ± 3.2 years, 4 patients underwent implantable cardioverter-defibrillator therapy for life-threatening ventricular arrhythmia and 3 patients finally underwent heart transplantation.Patients with persistent AF afflicted by CLMNA exhibit severe LA impairment because of large low-voltage areas, prolonged conduction velocity, and reduced contractile function. Ablation procedures have a limited effect with a high recurrence rate.

Background Epicardial ablation is occasionally limited by coronary artery (CA) injuries or epicardial fat (EF). Objective The purpose of this study was to evaluate the anatomic obstacles that prevent ablation of epicardial abnormal potentials (EAPs) in patients with Brugada syndrome (BrS) and to investigate the feasibility of EAP elimination by endocardial right ventricular (RV) ablation. Methods This study included 16 BrS patients with previous ventricular fibrillation (VF), including 10 with an electrical storm. Data from multidetector computed tomography were assessed, and the proximity of the CA and EF was correlated with EAPs. Results EAPs were present in the epicardial RV outflow tract and RV inferior wall in all patients and 12 patients (75%), respectively. These EAPs were present within 5 mm of the main body and branches of the right CA in 14 patients (87.5%). However, only 1.4% ± 2.9% of the EAP area was covered with thick EF (≥8 mm). Partial EAP elimination by endocardial RV ablation was feasible in all 10 patients, with 53.3% successful endocardial RV radiofrequency applications for eliminating EAPs. After the procedure, VF remained inducible in 37.5% of the patients. During the 25.1 ± 29.1 months of follow-up, no patients experienced an electrical storm, and VF burden significantly decreased (median VF episodes before and after ablation: 7 and 0, respectively). Conclusion EAPs are near the CA in most BrS patients, thereby requiring caution during epicardial ablation, whereas EF is less of an issue. Endocardial ablation is feasible to eliminate some EAPs and may be combined with epicardial ablation.

Background: Achieving bidirectional mitral isthmus (MI) block using radiofrequency catheter ablation (RFCA) alone is challenging, and MI reconnection is common. Adjunctive vein of Marshall (VOM) ethanol infusion (VOM-Et) can facilitate acute MI block. However, little is known about its long-term success. This study sought to evaluate the impact of adjunctive VOM-Et on MI block achievement and durability compared with RFCA alone. Methods: Patients undergoing the first attempt of posterior MI ablation were grouped according to their MI block index strategy: adjunctive VOM-Et and RFCA alone. Rates of acute MI block and MI reconnection observed during repeat procedures were compared between the 2 groups. Results: The VOM-Et group consisted of 152 patients (63.8±9.4 years) undergoing adjunctive VOM-Et for MI block. The RFCA group consisted of 110 patients (60.9±9.2 years) undergoing MI ablation using RFCA alone. Acute MI block was more frequently achieved in the VOM-Et group (98.7% [150/152] versus 63.6% [70/110]; P P P P =0.008). Conclusions: Beyond facilitating acute MI block, VOM-Et is associated with greater lesion durability as evidenced by higher rates of MI block during repeat procedures.

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

Coronary artery injury is a rare complication of catheter ablation in the right ventricular outflow tract (RVOT). Furthermore, acute myocardial ischemia usually causes polymorphic ventricular tachycardia (VT) or ventricular fibrillation. We herein describe a case in which catheter ablation for VT originating from the RVOT provoked ischemia-related VTs due to acute occlusion of the left anterior descending artery.

Background Gaps in the roof line have been ascribed to epicardial conduction using the septopulmonary bundle. Objectives We sought to evaluate the frequency of septopulmonary bundle bypass during roof line ablation, to describe anatomical conditions favoring this epicardial gap, and to propose an alternative strategy when present. Methods One hundred consecutive patients underwent atrial fibrillation ablation. A de novo roof line was created between the superior pulmonary veins. In cases of residual gaps, a floor line was created between the inferior pulmonary veins. Microtomography imaging and histological analyses of 5 human donor hearts were performed: a specific focus was made on the dome and the posterior wall. Results Residual gaps were more frequent in roof lines than floor lines (33% vs 15%; P = .049). Electrogram morphologies, activation sequences, and pacing maneuvers indicated an epicardial bypass of the roof line in all cases. Conduction block was obtained in 67 roof lines and 28 floor lines, resulting in a 95% success rate of linear block, without "box" isolation. Between the superior pulmonary veins, the atrial myocardium was thicker and consistently displayed adipose tissue separating the septopulmonary bundle from the septoatrial bundle. Conclusion Epicardial conduction across the roof line is common and requires careful electrogram analysis to detect. In such cases, a floor line can be an effective alternative strategy, with clear validation criteria. Myocardial thickness and fat interposition may explain difficulties in achieving lesion transmurality during roof line ablation.

Background Epicardial adipose tissue (EAT) contributes to atrial fibrillation (AF). However, its impact on the efficacy of left atrial posterior wall isolation (LAPWI) is unclear. Methods Forty‐four nonparoxysmal AF patients underwent LAPWI after pulmonary vein isolation. EAT overlap on LAPWI was assessed by fusing computed tomography images with electro‐anatomical mapping. Results During the 21 ± 7 months of follow‐up, AF recurred in 10 patients (23%). The total and left atrial EAT volumes were 113 ± 36 and 33 ± 12 cm3, respectively. No differences were found between the AF‐free and AF‐recurrent groups regarding EAT volume. The EAT overlaps on LAPWI lines and LAPWI area were 1.2 ± 1.0 and 0.5 ± 0.9 cm2 respectively. Although no difference was found between groups regarding the EAT overlap on LAPWI area, the AF‐free group had a significantly larger EAT overlap on LAPWI lines (1.4 ± 1.0 vs 0.6 ± 0.6 cm2, P = .014). Multivariate analysis identified EAT overlap on LAPWI lines as an independent predictor of AF recurrence (hazard ratio: 0.399, 95% confidence interval: 0.178‐0.891, P = .025). Kaplan‐Meier analysis revealed that, during follow‐up, 92% of the large EAT overlap group (≥1.0 cm2) and 58% of the small EAT overlap group (

BACKGROUND The effects of catheter ablation for atrial fibrillation (AF) on hemodynamic parameters in patients with preserved left ventricular (LV) systolic function are unclear. Methods and Results: We enrolled 178 patients with AF (paroxysmal, 108; persistent, 70) with preserved LV systolic function who underwent AF ablation. The stroke volume index (SVI) was repeatedly measured using impedance cardiography. Reduced SVI (SVI

Influence of left atrial wall thickness on outcome of catheter ablation for atrial fibrillation (AF) is unclear. Overall, 213 patients with AF (128 paroxysmal and 85 persistent) received ablation. We measured the wall thickness of 16 and 19 areas in the pulmonary vein antrum (PVWT) and left atrial body (LAWT), respectively. Coefficient of variation of wall thickness (CV-WT) was calculated to assess heterogeneity in the left atrial wall thickness. In patients with paroxysmal AF, maximum PVWT, mean PVWT, maximum LAWT, and CV-WT were higher in AF recurrent group than in AF-free group (maximum PVWT, 2.85 ± 0.52 vs. 2.50 ± 0.45 mm, P = 0.003; mean PVWT, 1.59 ± 0.13 vs. 1.50 ± 0.15 mm, P = 0.018; maximum LAWT, 3.85 ± 0.77 vs. 3.41 ± 0.61 mm, P = 0.005; CV-WT, 0.34 ± 0.06 vs. 0.32 ± 0.05, P = 0.039). In patients with persistent AF, maximum PVWT, mean PVWT, maximum LAWT, mean LAWT, and CV-WT were higher in the AF-recurrent group than in the AF-free group (maximum PVWT, 2.52 ± 0.36 vs. 2.31 ± 0.36 mm, P = 0.031; mean PVWT, 1.53 ± 0.12 vs. 1.45 ± 0.14 mm, P = 0.036; maximum LAWT, 3.68 ± 0.75 vs. 3.11 ± 0.50 mm, P

Vasovagal syncope (VVS) is known to have a benign prognosis and be associated with enhanced contraction and activation of the left ventricular (LV) mechanoreceptors. However, a little is known about VVS in patients with LV dysfunction. The present study aimed to investigate the prevalence and prognosis of VVS in patients with LV dysfunction. We enrolled 368 patients with unexplained syncope. In 7 of these patients, LV ejection fraction was lower than 40%. The results of a head-up tilt test (HUT) and the recurrence of syncope were compared between these 7 patients with LV dysfunction and the remaining patients. Positive HUT was obtained in the 6 patients (86%) with LV dysfunction; this rate tended to be higher as compared with normal cardiac function (192/361, 53%, P = 0.069). In patients with LV dysfunction, response in HUT was mostly vasodepressor type (62%); however, most of HUT responses were mixed type in patients with normal LV function (67%). Among patients with positive HUT, the recurrent rate of syncope after HUT was higher in those with LV dysfunction than in those with normal LV function (67 vs. 21%, P = 0.008). VVS in patients with LV dysfunction may be refractory to treatment and could be associated with poor prognosis.

Key Clinical Message Catheter ablation of atrial fibrillation is difficult when the left atrium is compressed by the vertebra. The heart may shift forward, and compression of the left atrium may be relieved in the left lateral decubitus position. Therefore, catheter ablation could be performed in the left lateral decubitus position even in such cases.

We aimed to optimize the acquisition of the left atrial (LA) and pulmonary vein (PV) ultrasound contours for more accurate integration of intracardiac echocardiography (ICE) and computed tomography (CT) using the CARTOEighty-five AF patients underwent integration of ICE and CT using (1) the LA roof and posterior wall contours acquired from the right atrium (RA), (2) all LA/PV contours from the RA (Whole-RA-integration), (3) the LA roof/posterior wall contours from the RA and right ventricular outflow tract (RVOT) (Posterior-RA/RV-integration), and (4) all LA/PV contours from the RA and RVOT (Whole-RA/RV-integration). The integration accuracy was compared using the (1) surface registration error, (2) distances between the three-dimensional CT and eight specific sites on the anterior, posterior, superior, and inferior aspects of the right and left circumferential PV isolation lines, and (3) registration score: a score of 0 or 1 was assigned for whether or not each specific site was visually aligned with the CT, and summed for each method (0 best, 8 worst).Posterior-RA/RV-integration revealed a significantly lower surface registration error (1.30±0.15mm) than Whole-RA- and Whole-RA/RV-integration (p0.001). The mean distances of the eight specific sites and the registration score for Posterior-RA/RV-integration (median 1.26mm and 2, respectively) were significantly smaller than those for the other integration approaches (p0.001).Image integration with the LA roof and posterior wall contours acquired from the RA and RVOT may provide greater accuracy for catheter navigation with three-dimensional CT during AF ablation.

Background: Atrial fibrillation ablation–related atrial tachycardia (AT) is complex and may demonstrate several forms: anatomic macroreentrant AT (AMAT), non-AMAT, and focal AT. We aimed to elucidate the recurrence rate and mechanisms of atrial fibrillation ablation–related AT recurrence. Methods: Among 147 patients with ATs treated with the Rhythmia system, 68 (46.3%) had recurrence at mean 4.2 (2.9–11.6) months, and 44 patients received a redo procedure. AT circuits in the first procedure were compared with those in the redo procedure. Results: Although mappable ATs were not observed in 7 patients, 68 ATs were observed in 37 patients during the first procedure: perimitral flutter (PMF) in 26 patients, roof-dependent macroreentrant AT (RMAT) in 18, peritricuspid flutter in 10, non-AMAT in 14, and focal AT in 3. During the redo AT ablation procedure, 54 ATs were observed in 41/44 patients: PMF in 24, RMAT in 14, peritricuspid flutter in 1, non-AMAT in 14, and focal AT in 1. Recurrence of PMF and RMAT was observed in 15 of 26 (57.7%) and 8 of 18 (44.4%) patients, respectively, while peritricuspid flutter did not recur. Neither the same focal AT nor the same non-AMAT were observed except in 1 case with septal scar–related biatrial AT. Epicardial structure–related ATs were involved in 18 of 24 (75.0%) patients in PMF, 4 of 14 (28.6%) in RMAT, and 4 of 14 (28.6%) in non-AMAT. Of 21 patients with a circuit including epicardial structures, 6 patients treated with ethanol infusion in the vein of Marshall did not show any AT recurrence, although 8 of 15 (53.3%) treated with radiofrequency showed AT recurrence ( P =0.04). Conclusions: Although high-resolution mapping may lead to correct diagnosis and appropriate ablation in the first procedure, the recurrence rate is still high. The main mechanism of atrial fibrillation ablation–related AT is the recurrence of PMF and RMAT or non-AMAT different from the first procedure. Epicardial structures (eg, coronary sinus/vein of Marshall system) are often involved, and ethanol infusion in the vein of Marshall may be an additional treatment.

Background: Various strategies for ablation of ventricular tachycardia (VT) have been described, but their impact on ventricular fibrillation (VF) is largely unknown. The aim of our study was to assess the effect of substrate-based VT ablation targeting local abnormal ventricular activity (LAVA) on recurrent VF events in patients with structural heart disease. Methods: A retrospective 2-center study was performed on patients with structural heart disease and both VT and VF, with incident VT ablation procedures targeting LAVAs. Generalized estimating equations with a Poisson loglinear model were used to assess the impact of catheter ablation on VF episodes. The change in VF events before and after catheter ablation was compared with matched controls without ablation. Results: From a total of 686 patients with an incident VT ablation procedure targeting LAVAs, 21 patients (age, 57±14 years; left ventricular ejection fraction, 30±10%) had both VT and VF and met inclusion criteria. A total of 80 VF events were recorded in the implantable cardioverter-defibrillator logs the 6 months preceding ablation. Complete and partial LAVA elimination was achieved in 11 (52%) and 10 (48%) patients, respectively. Catheter ablation was associated with a highly significant reduction in VF recurrences ( P P =0.0003). Conclusions: Substrate-guided VT ablation targeting LAVAs may be associated with a significant reduction in recurrent VF, suggesting that VT and VF share overlapping arrhythmogenic substrates in patients with structural heart disease.

Background Atrioventricular (AV) node duality is suggested by several electrophysiological findings, none of which are strong predictors of AV nodal reentrant tachycardia (AVNRT). Objective The purpose of this study was to propose a novel maneuver to study conduction over the AV node and attempt to induce slow-fast AVNRT. Methods Ventricular-triggered atrial pacing (VTAP) with decremental VA delay was carried out in 36 consecutive patients with slow-fast AVNRT and in 21 controls after conventional electrophysiology study. Maneuvers were repeated after ablation in patients with AVNRT. Results VTAP resulted in a hysteretic conduction curve in 21 of 36 patients (58%) in the AVNRT group but only 4 of 21 patients (19%) in the control group (sensitivity 58; specificity 81%). This finding demonstrates sustained conduction in a slow conducting pathway and concealed retrograde conduction over a fast pathway. VTAP resulted in AVNRT induction in 15 of 25 inducible patients at baseline (60%), 4 of which were not inducible with incremental pacing or programmed atrial stimulation. VTAP resulting in a suspended p wave had 51% (39%–64%) sensitivity and 100% (89%–100%) specificity for predicting noninducibility in a given autonomic state. Conclusion VTAP is useful in patients with suspected slow-fast AVNRT. A hysteretic conduction curve demonstrates sustained conduction over a slow pathway and concealed retrograde conduction through the fast pathway, a finding in favor of slow-fast AVNRT. VTAP may facilitate AVNRT induction and proves to be an interesting complement to classic maneuvers. A suspended p-wave response specifically predicts noninducibility of slow-fast AVNRT in a given autonomic state, providing an interesting surrogate to noninducibility as a procedural end point.

Background P-wave amplitude (PWA) parameters can be the surrogate measures of the left atrial low-voltage areas (LVAs). Methods We measured PWAs using an automated system in 50 patients with paroxysmal atrial fibrillation (AF). We examined the relationships between left atrial LVAs and PWA parameters, including P-wave vector magnitude, calculated as the square root of the sum of lead II PWA squared, lead V6 PWA squared, and a one-half lead V2 PWA squared. Results Lead I PWA was most strongly correlated with LVAs in the anterior wall and appendage (anterior wall, R = −0.391, P = 0.006; appendage, R = −0.342, P = 0.016), whereas lead II PWA was most strongly correlated with LVAs in the septum, posterior wall, and bottom wall (septum, R = −0.413, P = 0.003; posterior wall, R = −0.297, P = 0.039; bottom wall; R = −0.288, P = 0.045). Although maximum, minimum, mean, and lead I PWAs were not correlated with total LVA, P-wave vector magnitude and lead II PWA were significantly correlated with total LVA (P-wave vector magnitude, R = −0.430, P = 0.002; lead II PWA, R = −0.323, P = 0.023). P-wave vector magnitude achieved the highest accuracy for predicting significant LVA (total LVA > 10%) with an area under the curve of 0.772; sensitivity, specificity, and positive and negative predictive values were 64%, 88%, 85%, and 69%, respectively, for the cutoff value of 0.130 mV. Conclusion P-wave vector magnitude is a useful electrocardiographic predictor of left atrial LVAs.

We determined the role of persistent monoarthritis of temporomandibular joint region (TMJ) on bilateral masseter muscle (MM) nociception in male rats using orofacial nocifensive behaviors, phosphorylated extracellular signal-regulated kinase and Fos induction at the trigeminal subnucleus caudalis/upper cervical spinal cord (Vc/C2) region in response to formalin injection to the MM region. TMJ inflammation was induced by local injection of CFA into the left TMJ region. Orofacial nocifensive behaviors evoked by formalin injection ipsilateral or contralateral to the TMJ inflammation appeared to be increased at 1–14 days or at 1, 10 and 14 days after induction of TMJ inflammation, respectively, while increases in behavioral duration were seen mainly in the late phase rather than the early phase. The number of pERK positive cells was investigated in superficial laminae at the Vc/C2 region at 3, 10, 20, 60 and 80 min after MM stimulation with formalin at 14 days after TMJ inflammation. TMJ-inflamed rats displayed greater responses of pERK expression by the ipsilateral MM stimulation at 3–60 min, while contralateral MM stimulation increased pERK expression at 3, 10 and 20 min compared to non-CFA rats. Fos expression by MM stimulation was increased at 14 days after induction of TMJ inflammation regardless of the affected side. These findings showed that persistent TMJ inflammation for 10 and 14 days is sufficient to enhance MM nociception indicated by behaviors and neural responses in superficial laminae at the Vc/C2 region.

KCNE1 encodes a modulator of KCNQ1 and KCNH2 channels. Although KCNE1(G38S), a single-nucleotide polymorphism (SNP) causing a G38S substitution in KCNE1, is found frequently, whether and how this SNP causes long QT syndrome (LQTS) remains unclear. We evaluated rate-dependent repolarization dynamics using Holter electrocardiogram (ECG) to assess the pathogenicity of KCNE1(G38S). Forty-five patients exhibiting long QT intervals, as assessed by their baseline ECGs, and 16 control subjects were enrolled. KCNE1(G38S) carriers were identified using genome sequencing. LQTS patients were classified into LQT1 or LQT2 using genetic analysis or epinephrine test. QT–RR relations were determined using 24-h Holter ECG recordings. Among the 15 patients (33.3 %) with KCNE1(G38S), four patients without any mutations or amino acid changes in other major cardiac ion channels were categorized as KCNE1(G38S) carriers. In the QT–RR regression lines, the QT–RR slope was greater in the KCNE1(G38S) carriers and the LQT2 patients (0.215 ± 0.021 and 0.207 ± 0.032, respectively) than in the LQT1 patients (0.163 ± 0.014, P

Coefficient of Variation of P-Wave and AF Recurrence Introduction Atrial conduction heterogeneity is associated with progression of atrial fibrillation (AF). However, the relationship between P-wave parameters representing atrial conduction heterogeneity and AF recurrence after catheter ablation (ABL) is still unclear. Methods and Results Subjects of the study were 126 consecutive patients with AF (78 paroxysmal and 48 persistent) who had received ABL. Coefficient of variation of P-wave duration (CV-PWD) was determined with all 12 surface electrocardiographic leads as an index of atrial conduction heterogeneity. Rates of freedom from AF recurrence were 78% and 77% in patients with paroxysmal and persistent AF, respectively, over a 12-month follow-up. CV-PWD measured before ABL was smaller in AF-free patients compared with AF-recurrent patients (0.089 ± 0.019 vs. 0.129 ± 0.042, P < 0.001). CV-PWD significantly decreased after ABL in AF-free patients, but did not change in AF-recurrent patients. CV-PWD after ABL was also smaller in AF-free patients compared with AF-recurrent patients (0.087 ± 0.025 vs. 0.133 ± 0.035, P < 0.001). In receiver operating curve analysis, CV-PWD before and after ABL achieved area under the curve of 0.829 and 0.854, respectively, for the ability to predict AF recurrence. CV-PWD correlated positively with left atrial (LA) diameter and negatively with LA appendage flow velocity. Conclusion CV-PWD is a useful index to predict AF recurrence after ABL for both patients with paroxysmal and persistent AF. ABL may suppress AF by decreasing atrial conduction heterogeneity.

BACKGROUND: The predictive efficacies of parameters related to P‐wave amplitude (PWA) for atrial fibrillation (AF) recurrence after catheter ablation are unclear. METHODS: We measured multiple PWA parameters using an automated system in 126 consecutive patients with persistent and long‐standing persistent AF who underwent catheter ablation. The relationships between AF recurrence and various PWA parameters were examined, including the association with P‐wave vector magnitude (calculated as the square root of the sum of lead II PWA squared, lead V6 PWA squared, and a one‐half lead V2 PWA squared). RESULTS: Atrial fibrillation did not recur in 87 patients (69%) during 32 ± 15 months of follow‐up. The maximum PWA, mean PWA, and P‐wave vector magnitude were lower in patients with AF recurrence than those without (maximum PWA, 0.14 ± 0.05 mV vs. 0.16 ± 0.05 mV, p = 0.017; mean PWA, 0.05 ± 0.02 mV vs. 0.06 ± 0.02 mV, p = 0.003; P‐wave vector magnitude, 0.09 ± 0.03 mV vs. 0.13 ± 0.04 mV, p

The increased body size correlates with the occurrence of atrial fibrillation (AF); however, the impact of the body size on the AF recurrence after ablation remains unclear. We enrolled 283 AF patients (179 paroxysmal, 51 persistent, and 53 long-standing persistent) who received ablation and assessed the correlation between the body surface area (BSA) and the AF recurrence. Furthermore, we measured the left atrial wall thickness using computed tomography. During the 12-month follow-up period, the AF freedom rates for patients with paroxysmal AF, persistent AF, and long-standing persistent AF were 83%, 76%, and 77%, respectively. The left atrial dimension, BSA, and body mass index (BMI) were higher in the AF-recurrent group compared with the AF-free group (left atrial dimension: 44.1 ± 7.5 mm vs. 41.7 ± 6.5 mm, P = 0.019; BSA: 1.81 ± 0.20 m2 vs. 1.72 ± 0.19 m2, P = 0.002; BMI 25.0 ± 3.2 kg/m2 vs. 24.0 ± 3.2 kg/m2, P = 0.035). The multivariate analysis revealed that only the BSA was an independent predictor of the AF recurrence after ablation (hazard ratio 6.843; 95% confidence interval 1.523–30.759, P = 0.012). The BSA significantly correlated with the left atrial wall thickness (R = 0.306, P

Coagulation factor Xa activates the protease-activated receptor 2 (PAR2) and causes tissue fibrosis; however, the effects of Xa inhibitor edoxaban on atrial fibrosis and atrial fibrillation (AF) have not been investigated. We examined the effect of edoxaban on the progression of atrial fibrosis in a canine congestive heart failure (CHF) model. Beagle dogs were assigned to sham, placebo, and edoxaban groups (n = 6/group). Dogs of the placebo or edoxaban groups received 19 days of medication with daily oral placebo or edoxaban, respectively, followed by 14 days of ventricular tachypacing. Dogs of the sham group had no medication or pacing. Ventricular tachypacing prolonged AF duration in dogs of the placebo group (159 ± 41 s, p

Swallow syncope is a relatively rare syndrome and caused by various foods and drinks. A 76-year-old man was admitted with frequent syncope while eating. Holter electrocardiogram revealed frequent occurrence of atrioventricular block during meals. Both atrioventricular block and sinus arrest were induced by only eating citrus fruits, citrus jelly, and acidic foods but not by other drinks and foods. These arrhythmias were suppressed after administration of atropine. No further episodes of syncope recurred after the implantation of a DDD pacemaker. This case indicated that acidic stimulation of citrus induced a vasovagal reflex via esophageal nociceptors leading to syncope.

BACKGROUND This study aimed to clarify whether retrograde P-wave amplitude during tachycardia can be used to differentiate slow-slow form of atrioventricular nodal reentrant tachycardia (S/S-AVNRT) from atrioventricular reentrant tachycardia through a posteroseptal accessory pathway (PS-AVRT). METHODS Sixteen patients with S/S-AVNRT and 14 patients with PS-AVRT constituted the study group. Electrocardiographic and electrophysiological parameters were compared between both the groups. HA(CS-His), which indicates the location of the earliest atrial activation site during tachycardia, was calculated as the difference of the shortest HA interval in the His bundle region and the coronary sinus region. RESULTS Negative deflection of the retrograde P wave during tachycardia was significantly greater in S/S-AVNRT than in PS-AVRT in the inferior leads (lead aVF, -0.22 ± 0.04 mV vs -0.10 ± 0.07 mV; P < 0.001). Among the electrocardiographic parameters, retrograde P-wave amplitude in lead aVF had the highest diagnostic accuracy (area under the curve 0.975, sensitivity 93%, and specificity 88% for a cutoff value of -0.16 mV). HA(CS-His) was negatively greater in S/S-AVNRT than in PS-AVRT (-24 ± 13 ms vs -3 ± 18 ms; P = 0.001), and was significantly correlated with the retrograde P-wave amplitude in lead aVF (P = 0.004). CONCLUSION Deeper negative deflection of the retrograde P wave in the inferior lead can help differentiate S/S-AVNRT from PS-AVRT.

BACKGROUND Little is known about time-dependent changes in QT dynamics after initiation of atrial fibrillation (AF) and after restoration of sinus rhythm (SR) in patients with paroxysmal AF. METHODS Beat-to-beat QT and RR intervals in CM5 lead were measured automatically in 13 patients with both AF and SR on the single 24-hour Holter electrocardiology recording. QT-RR relation was analyzed at six periods of time: 1 hour before AF onset (Pre(0-1h)), 0-1 hour and 4-5 hours after AF onset (AF(0-1h) and AF(4-5h)), and 0-1 hour, 2-3 hours, and 4-5 hours after the restoration of SR (SR(0-1h), SR(2-3h), and SR(4-5h)). RESULTS QT-RR slope was gradually decreased after AF onset and gradually returned to the baseline level after restoration of SR. The slope became greater at SR(4-5h) than at AF(4-5h) and AF(0-1h). In patients receiving antiarrhythmic drugs (AADs; n = 5), QT-RR slope was greater at SR(4-5h) than in those not receiving AADs (n = 8). CONCLUSION In patients with paroxysmal AF, bradycardia-dependent QT prolongation was attenuated during AF, and was corrected and gradually augmented along with continuation of SR, especially in patients receiving AADs. This could increase the risk of developing torsade de pointes.

We prospectively investigated the differences in pulmonary vein reconnections (PVRs) and clinical outcomes between contact force (CF)-guided and conventional circumferential PV isolation (CPVI) of atrial fibrillation (AF). One hundred twenty consecutive AF patients (63 ± 10 years; 88 males) undergoing an initial CPVI were randomized to ablation with a target CF of 20 g (CF group; n = 60) or that with operators blinded to the CF information (blind group; n = 60). The CF group had fewer PVRs (0.67 ± 0.91/patient vs. 1.16 ± 1.16/patient; P = 0.007), a lower incidence of persistent PVRs (13.2 vs. 41.2 %; P

Background Epicardial adipose tissue (EAT) is located adjacent to high dominant frequency (DF) sites. Objective This study aimed to clarify the relationship between the EAT location and efficacy of a combined high DF site and continuous complex fractionated activation electrogram (CFAE) site ablation. Methods Fifty-five patients with nonparoxysmal atrial fibrillation (AF) (26 (47%) persistent and 29 (53%) long-standing persistent) underwent pulmonary vein isolation followed by high DF site and continuous CFAE site ablation. High DF sites (DF ≥8 Hz) and continuous CFAE sites (fractionated intervals ≤50 ms) were targeted. The patients were divided into an AF-free group and an AF-recurrent group. Results The AF freedom rate on antiarrhythmic drugs in patients with persistent and long-standing persistent AF was 88.5% and 75.9% over a 12-month follow-up period, respectively. The total EAT, left atrial (LA)–EAT, and right atrial (RA)–EAT volumes did not indicate significant differences between the AF-free and AF-recurrent groups. In the LA, the overlap between high DF sites and EAT was larger in the AF-free group than in the AF-recurrent group (57.0% ± 33.3% vs 22.6% ± 23.3%; P .01). However, this overlap did not differ between the AF-free and AF-recurrent groups in the RA (20.4% ± 28.2% vs 19.0% ± 24.4%; P = .91). The overlap between continuous CFAE sites and EAT did not differ between the 2 groups in both the LA and the RA. Conclusion High DF sites that overlap with EAT may be important sources of AF. However, the contribution of EAT to the AF substrate may differ between the LA and the RA.

Background KCNE1 encodes a modulator of KCNH2 and KCNQ1 delayed rectifier K(+) current channels. KCNE1 mutations might cause long QT syndrome (LQTS) by impairing KCNE1 subunit's modulatory actions on these channels. There are major and minor polymorphismic KCNE1 variants whose 38(th) amino acids are glycine and serine [KCNE1(38G) and KCNE1(38S) subunits], respectively. Despite its frequent occurrence, the influence of this polymorphism on the K(+) channels' function is unclear. Methods and results Patch-clamp recordings were obtained from human embryonic kidney -293T cells. KCNH2 channel current density in KCNE1(38S)-transfected cells was smaller than that in KCNE1(38G)-transfected cells by 34%. The voltage-sensitivity of the KCNQ1 channel current in KCNE1(38S)-transfected cells was lowered compared to that in KCNE1(38G)-transfected cells, with a +13mV shift in the half-maximal activation voltage. KCNH2 channel current density or KCNQ1 channel voltage-sensitivity was not different between KCNE1(38G)-transfected cells and cells transfected with both KCNE1(38G) and KCNE1(38S). Moreover, the KCNH2 channel current in KCNE1(38S)-transfected cells was more susceptible to E4031, a QT prolonging drug and a condition with hypokalemia, than that in KCNE1(38G)-transfected cells. Conclusions Homozygous inheritance of KCNE1(38S) might cause a mild reduction of the delayed rectifier K(+) currents and might thereby increase an arrhythmogenic potential particularly in the presence of QT prolonging factors. By contrast, heterozygous inheritance of KCNE1(38G) and KCNE1(38S) might not affect the K(+) currents significantly. (Circ J 2014; 78: 610-618).

ObjectivesThis study sought to assess the effects of tranilast on atrial remodeling in a canine atrial fibrillation (AF) model.BackgroundTranilast inhibits transforming growth factor (TGF)-β1 and prevents fibrosis in many pathophysiological settings. However, the effects of tranilast on atrial remodeling remain unclear.MethodsBeagles were subjected to atrial tachypacing (400 beats/min) for 4 weeks while treated with placebo (control dogs, n = 8) or tranilast (tranilast dogs, n = 10). Sham dogs (n = 6) did not receive atrial tachypacing. Atrioventricular conduction was preserved. Ventricular dysfunction developed in the control and tranilast dogs due to rapid ventricular responses.ResultsAtrial fibrillation duration (211 ± 57 s) increased, and AF cycle length and atrial effective refractory period shortened in controls, but these changes were suppressed in tranilast dogs (AF duration, 18 ± 10 s, p < 0.01 vs. control). The L-type calcium channel α1c (Cav1.2) micro ribonucleic acid expression decreased in control dogs (sham 1.38 ± 0.24 vs. control 0.65 ± 0.12, p < 0.01), but not in tranilast dogs (0.97 ± 0.14, p = not significant vs. sham). Prominent atrial fibrosis (fibrous tissue area, sham 0.8 ± 0.1 vs. control 9.3 ± 1.3%, p < 0.01) and increased expression of tissue inhibitor of metalloproteinase protein 1 were observed in control dogs but not in tranilast dogs (fibrous tissue area, 1.4 ± 0.2%, p < 0.01 vs. control). The TGF-β1 (sham 1.00 ± 0.07 vs. control 3.06 ± 0.87, p < 0.05) and Rac1 proteins were overexpressed in control dogs, but their overexpression was inhibited in tranilast dogs (TGF-β1, 1.28 ± 0.20, p < 0.05 vs. control).ConclusionsTranilast prevented atrial remodeling and suppressed AF development in a canine model. Its inhibition of TGF-β1 and Rac1 overexpression may contribute to its antiremodeling effects.

Effects of an angiotensin II receptor blocker, irbesartan (IRB), on the development of atrial fibrosis and atrial fibrillation (AF) were assessed in a canine model of atrial tachycardia remodeling (ATR) with left ventricular dysfunction, together with its possible association with involvement of p53. Atrial tachypacing (400 bpm for 4 weeks) was used to induce ATR in beagles treated with placebo (ATR-dogs, n = 6) or irbesartan (IRB-dogs, n = 5). Non-paced sham dogs served as control (Control-dogs, n = 4). ATR- and IRB-dogs developed tachycardia-induced left ventricular dysfunction. Atrial effective refractory period (AERP) shortened (83 ± 5 ms, p

Although J-wave elevation in the inferolateral leads could be related to idiopathic ventricular fibrillation (IVF), little is known about the pathophysiologic characteristics of J-wave elevation in patients with IVF.This study aimed to determine the relationship between augmentation of J-wave elevation and changes in RR interval or autonomic nervous activities in patients with IVF.Eight patients with IVF and 22 controls with J-wave elevation (≥0.1 mV) in lead V5 were studied. The J-wave amplitude was automatically measured in lead CM5 of a digital Holter electrocardiogram, and the J-RR relationship was determined. Based on the analysis of heart rate variability, the relationship between the J-wave amplitude and the natural logarithm of high-frequency (HF) components (J-ln HF relationship) or the ratio of low frequency (LF) components to HF components (J-LF/HF relationship) was also determined.The J-RR slope (mm/s) was greater in patients with IVF than in controls (3.5 ± 0.7 vs 2.4 ± 0.8; P.01), as was J-wave amplitude (mm) at an RR interval of 1.2 seconds (2.8 ± 0.9 vs 2.0 ± 0.6; P.05). The J-wave amplitude was correlated positively with ln HF and negatively with LF/HF, and the slopes of both J-ln HF and J-LF/HF regression lines were greater in patients with IVF than in controls. During an entire 24-hour period, there was no difference between the 2 groups in either HF or LF/HF. Nine of the total 11 episodes (82%) of spontaneous ventricular fibrillation occurred between 18:00 and 6:00.In patients with IVF as compared with control subjects, J-wave elevation was more strongly augmented during bradycardia and was associated with an increase in vagal activity. This could be related to the occurrence of ventricular fibrillation predominantly at night in patients with IVF.