Complete free wall isolation of arrhythmogenic persistent left superior vena cava.

INTRODUCTION: Persistent left superior vena cava (PLSVC) is one of the major sources of triggers and drivers of atrial fibrillation (AF). There has been no established PLSVC ablation procedure to eliminate the arrhythmogenicity along the entire length of PLSVC. METHODS AND RESULTS: A 70-year-old woman with a history of two previous catheter ablations for AF, mitral valvuloplasty, and an unroofed coronary sinus-type atrial septal defect closure underwent the redo AF ablations. The AF trigger and driver were identified within the patient's enlarged PLSVC. The AF was treated by complete PLSVC free wall isolation. CONCLUSION: Complete PLSVC free wall isolation may be an effective ablation method to eliminate the arrhythmogenicity along the entire length of the PLSVC.

Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

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

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

Sex Differences in the Efficacy of Pulmonary Vein Isolation Alone vs. Extensive Catheter Ablation in Patients With Persistent Atrial Fibrillation.

BACKGROUND: Women experience more severe arrhythmogenic substrates. This study hypothesized that an extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might be effective for women, whereas the PVI alone strategy (PVI-alone) might be sufficient for men to maintain sinus rhythm. The aim of this study was to test this hypothesis.Methods and Results: This study is a post-hoc subanalysis of the EARNEST-PVI trial focusing on sex differences in the efficacies of different ablation strategies. The EARNEST-PVI trial was a prospective, multicenter, randomized, and open-label non-inferiority trial in patients with persistent AF. The primary endpoint was recurrence of AF, atrial flutter, or atrial tachycardia. The EARNEST-PVI trial randomized 376 (76%) men (PVI-alone 186, PVI-plus 190) and 121 (24%) women (PVI-alone 63, PVI-plus 58). The event rate was significantly lower for men and numerically lower for women in the PVI-plus than the PVI-alone group, and there was no interaction between men and women (hazard ratio, 0.641; 95% confidence interval, 0.417-0.985; P value, 0.043 for men vs. hazard ratio, 0.661; 95% confidence interval, 0.352-1.240; P value, 0.197 for women; P value for interaction, 0.989). CONCLUSIONS: The superiority of the extensive ablation strategy vs. the PVI-alone strategy for persistent AF was consistent across both sexes.

Post-ablation left atrial function impacts long-term recurrence of atrial fibrillation after ablation.

Left atrial (LA) function can help predict various cardiovascular events. Catheter ablation for atrial fibrillation (AF) modifies baseline LA function through the maintenance of sinus rhythm and myocardial injury. We investigated the impact of post-ablation LA function on recurrence of AF after ablation and identified the predictors of reduced post-ablation LA function. A total of 616 patients who underwent AF ablation (paroxysmal, N = 310; non-paroxysmal, N = 306) were retrospectively examined with cardiac computed tomography at baseline and 3 months after the final ablation procedure. Post-ablation LA emptying fraction (LAEFpost) was calculated. We evaluated the association between LAEFpost and recurrence of AF after the final ablation procedure. Further, we assessed the predictors of reduced LAEFpost. The recurrence rate of AF was 72.7% after the final ablation procedure [median follow-up 48 months (48.0, 48.0), total number of ablation sessions: 1.4 ± 0.7]. Multivariate analysis revealed that LAEFpost was associated with the recurrence of AF (hazard ratio/10% increase: 0.62, 95% confidence interval: 0.51-0.75, P < 0.0001). LAEFpost had a mild predictive power for recurrence of AF (c-statistics: 0.670, optimal cutoff: 26.36%, P < 0.0001). The recurrence-free proportion among patients with reduced LAEFpost (< 26.36%, N = 100) and those with preserved LAEFpost (≥ 26.36%, N = 516) was 40% and 79%, respectively (P < 0.0001). The predictors of reduced LAEFpost were low pre-ablation LAEF, high pre-ablation LA volume, low body mass index (BMI), and female sex. Further, reduced LAEFpost was associated with the total number of ablation sessions and extra-pulmonary vein LA ablation. In conclusion, reduced LAEFpost was associated with recurrence of AF after ablation. Advanced LA remodeling, low BMI, and female sex could predict reduced LAEFpost. Although additional ablation was associated with reduced LAEFpost, it remains unclear whether reduced LAEFpost resulted from the additional ablation. Reduced LAEFpost might help stratify patients with ablation-refractory AF.

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

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

Pulmonary vein isolation alone vs. more extensive ablation with defragmentation and linear ablation of persistent atrial fibrillation: the EARNEST-PVI trial.

AIMS: Previous studies could not demonstrate any benefit of more intensive ablation in addition to pulmonary vein isolation (PVI) including complex fractionated atrial electrogram (CFAE) and linear ablation for recurrence in the initial catheter ablation of persistent atrial fibrillation (AF). This study aimed to establish the non-inferiority of PVI alone to PVI plus these additional ablation strategies. METHODS AND RESULTS: Patients with persistent AF who underwent an initial catheter ablation (n = 512, long-standing persistent AF; 128 cases) were randomly assigned in a 1:1 ratio to either PVI alone (PVI-alone group) or PVI plus CFAE and/or linear ablation (PVI-plus group). After excluding 15 cases who did not receive procedures, we analysed 249 and 248 patients, respectively. The primary endpoint was recurrence of AF, atrial flutter, and/or atrial tachycardia, and the non-inferior margin was set at a hazard ratio of 1.43. In the PVI-plus group, 85.1% of patients had linear ablation and 15.3% CFAE ablation. After 12 months, freedom from the primary endpoint occurred in 71.3% of patients in the PVI-alone group and in 78.3% in the PVI-plus group [hazard ratio = 1.56 (95% confidence interval: 1.10-2.24), non-inferior P = 0.3062]. The procedure-related complication rates were 2.0% in the PVI-alone group and 3.6% in the PVI-plus group (P = 0.199). CONCLUSION: This randomized trial did not establish the non-inferiority of PVI alone to PVI plus linear ablation or CFAE ablation in patients with persistent AF, but implied that the PVI plus strategy was promising to improve the clinical efficacy (NCT03514693).

Efficacy of Extensive Ablation for Persistent Atrial Fibrillation With Trigger-Based vs. Substrate-Based Mechanisms　- A Prespecified Subanalysis of the EARNEST-PVI Trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) would be effective for modification of non-pulmonary vein (non-PV) substrates, whereas PVI might be sufficient for elimination of PV triggers. This study aimed to test the hypothesis that in patients with reproducible atrial fibrillation (AF) triggered by premature atrial contractions originating only from PVs, PVI alone can be sufficient to maintain sinus rhythm.Methods and Results:This study is a prespecified subanalysis of the EARNEST-PVI randomized controlled trial. This study investigated the efficacy of the PVI-alone strategy (PVI-alone) in comparison with the extensive strategy (PVI-plus) for persistent AF with a trigger-based mechanism vs. a substrate-based mechanism. Patients were stratified into 3 groups based on AF mechanisms: (1) Substrate group (N=236); (2) PV trigger group (N=236); and (3) non-PV trigger group (N=24). The hazard ratios for AF recurrence of the PVI-alone strategy with reference to the PVI-plus strategy were 1.456 (95% confidence interval [CI] [0.864-2.452]) in the substrate group, 1.648 (95% CI 0.969-2.801) in the PV trigger group, and 0.937 (95% CI 0.252-3.488) in the non-PV trigger group. No significant interaction between ablation strategy and AF mechanism was observed (P for interaction=0.748). CONCLUSIONS: This study indicated that the efficacies of the PVI-alone strategy compared with the PVI-plus strategy were consistent across persistent AF with trigger-based and substrate-based mechanisms.

Sex differences in atrial fibrillation ablation outcomes: insights from a large-scale multicentre registry.

AIM: The impact of sex differences on the clinical outcomes of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is controversial. We investigated the sex differences regarding the efficacy and clinical outcomes of RFCA of AF. METHODS AND RESULTS: We conducted a large-scale, prospective, multicentre, observational study (Kansai Plus Atrial Fibrillation Registry). We enrolled 5010 consecutive patients who underwent an initial RFCA of AF at 26 centres (64 ± 10 years; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Female patients (n = 1369, 27.3%) were older (female vs. male, 68 ± 9 vs. 63 ± 11 years, P < 0.0001) with a lower prevalence of non-paroxysmal AF (27.1% vs. 38.9%, P < 0.0001). Fewer females experienced time-dependent pulmonary vein (PV) reconnections and more females received a non-PV foci ablation than males in the index RFCA. The 3-year cumulative incidence of AF recurrences in the multivariate analysis after single procedures was significantly higher in females than males (43.3% vs. 39.0%, log rank P = 0.0046). Females remained an independent predictor of AF recurrence (hazard ratio 1.24; 95% confidence interval 1.12-1.38, P < 0.0001). The AF recurrence rates after multiple procedures were also higher in females, but fewer females experienced PV reconnections during second sessions. More females experienced de novo pacemaker implantations during the long-term follow-up. Females were associated with a higher risk of heart failure hospitalizations and major bleeding after RFCA in the multivariate analysis. CONCLUSIONS: Females experienced more frequent AF recurrences probably due to non-PV arrhythmogenicity and de novo pacemaker implantations than males during the long-term follow-up after RFCA of AF.

Burden and Long Firing of Premature Atrial Contraction Early After Catheter Ablation Predict Late Recurrence of Atrial Fibrillation.

BACKGROUND: Associations between characteristics of premature atrial contraction (PAC) 6 months after catheter ablation (CA) and later recurrence are not known. We investigated the effects of PAC characteristics on long-term outcomes of initially successful atrial fibrillation (AF) ablation.Methods and Results:In all, 378 patients (mean age 61 years, 21% female, 67% paroxysmal AF) who underwent initial radiofrequency CA for AF without recurrence up to 24-h Holter monitoring 6 months after the procedure were reviewed retrospectively. The calculated number of PAC/24 h and the length of the longest PAC run during Holter recording were analyzed. After 4.3±1.2 years (mean±SD) follow-up, 123 (32.5%) patients experienced late recurrence. Patients with recurrence had significantly more PAC/24 h (median [interquartile range] 110 [33-228] vs. 42 [16-210]; P<0.01) and a longer longest PAC run (5 [2-8] vs. 3 [1-5]; P<0.01) than those without. Receiver operating characteristic curve analysis indicated 58 PAC/24 h and a longest PAC run of 5 were optimal cut-off values for predicting recurrence. After adjusting for previously reported predictors of late recurrence, frequent PAC (≥58/24 h) and longest PAC run ≥5 were found to be independent predictors of late recurrence (hazard ratios [95% confidence intervals] 1.93 [1.24-3.02; P<0.01] and 1.81 [1.20-2.76; P<0.01], respectively). CONCLUSIONS: Six months after successful AF ablation, both frequent PAC and long PAC run are independent predictors of late recurrence.

Comparison of the Safety and Efficacy of Automated Annotation-Guided Radiofrequency Ablation and 2nd-Generation Cryoballoon Ablation in Paroxysmal Atrial Fibrillation.

BACKGROUND: Automated ablation lesion annotation with optimal settings for parameters including contact force (CF) and catheter stability may be effective for achieving durable pulmonary vein isolation. Methods and Results: We retrospectively examined 131 consecutive patients who underwent initial catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) by automatic annotation system (VISITAG module)-guided radiofrequency CA (RFCA) (n=61) and 2nd-generation cryoballoon ablation (CBA) (n=70) in terms of safety and long-term efficacy. The automatic annotation criteria for the RFCA group were as follows: catheter stability range of motion ≤1.5 mm, duration ≥5 s, and CF ≥5 g. We ablated for >20 s with a force-time integral >150 gs at each site, before moving to the next site. Each interlesion distance was <6 mm. Procedural complications were more frequent in the CBA group (1.6% vs. 10.0%, P=0.034). Across a median follow-up of 2.98 years, 88.5% and 70.0% of patients in the RFCA and CBA groups, respectively, were free from recurrence (log-rank test, P=0.0039). There was also a significant difference in favor of RFCA with respect to repeat ablations (3.3% vs. 24.3%, log-rank test, P=0.0003). CONCLUSIONS: RF ablation guided by an automated algorithm that includes CF and catheter stability parameters showed better long-term outcomes than CBA in the treatment of patients with PAF without increasing complications.

Multiple Shifts of the Earliest Retrograde Atrial Activation Site Along the Tricuspid Annulus During the Fast-Slow Form of Atrioventricular Nodal Reentrant Tachycardia by Radiofrequency Modification.

A 70-year-old woman was admitted for treatment of supraventricular tachycardia. Ventriculoatrial conduction was revealed through programmed ventricular stimulation; the coronary sinus ostium (CSos) was the earliest atrial activation site. The fast-slow forms of atrioventricular nodal reentrant tachycardia (AVNRT) were induced by ventricular extra-stimuli. During tachycardia, the earliest atrial activation site was located at the bottom of CSos. Radiofrequency (RF) energy application to this site resulted in the delay of local electrical potential, prolongation of tachycardia cycle length, and a shift of the earliest retrograde activation site to the roof of CSos. Subsequent ablation induced a similar shift to the inferior tricuspid annulus and to the right posterior septum. Finally, RF energy application to the right posterior septum resulted in the termination of tachycardia, which was not induced afterward. Multiple shifts in the earliest retrograde atrial activation site along the tricuspid annulus after each slow pathway ablation suggested that annular tissue plays a substantial role as a substrate for AVNRT.

Effect of QRS Morphology and Duration on Clinical Outcomes After Cardiac Resynchronization Therapy　- Analysis of Japanese Multicenter Registry.

BACKGROUND: QRS duration (QRSd) and morphology are established response predictors of cardiac resynchronization therapy (CRT). However, evidence in Japanese populations is lacking.Methods and Results:We retrospectively analyzed the Japanese multicenter CRT database. We divided patients according to their intrinsic QRSd and morphology, and assessed echocardiographic responses and clinical outcomes. The primary endpoint was a composite of all-cause death or hospitalization because of heart failure. A total of 510 patients were enrolled: 200 (39%) had left bundle branch block (LBBB) and QRSd ≥150 ms; 80 (16%) had LBBB (QRSd: 120-149 ms); 61 (12%) had non-LBBB (NLBBB) (QRSd: ≥150 ms); 54 (11%) had NLBBB (QRSd: 120-149 ms); 115 (23%), narrow (<120 ms). The proportion of echocardiographic responders was higher in LBBB (QRSd ≥150 ms) [74% vs. 51% vs. 38% vs. 52% vs. 50%, LBBB (QRSd ≥150 ms) vs. LBBB (QRSd 120-149 ms) vs. NLBBB (QRSd ≥150 ms) vs. NLBBB (QRSd 120-149 ms) vs. narrow, respectively, P<0.001]. During follow-up (3.2±1.5 years), the incidence of the primary endpoint was lowest in the LBBB group (QRSd ≥150) (28.6% vs. 42.3% vs. 45.9% vs. 55.6% vs. 55.3%, respectively, P<0.001). This difference was still significant after adjusting for other baseline characteristics. CONCLUSIONS: In this Japanese patient population, LBBB intrinsic QRS morphology and prolonged QRSd (≥150 ms) exhibited the best response to CRT.

Efficacy and Safety of Figure-of-Eight Suture for Hemostasis After Radiofrequency Catheter Ablation for Atrial Fibrillation.

BACKGROUND: This study evaluated the safety and efficacy of venous figure-of-eight (FoE) suture to achieve femoral venous hemostasis after radiofrequency (RF) catheter ablation (CA) for atrial fibrillation (AF).Methods and Results:We retrospectively examined 517 consecutive patients undergoing RFCA for AF. The control group (n=247) underwent manual compression for femoral venous hemostasis after sheath removal with 6 h of bed rest. The FoE group (n=270) underwent FoE suture technique with 4 h of bed rest. All patients achieved successful hemostasis within 24 h after CA. Although the incidence of hematoma was similar between the groups, the incidence of rebleeding was lower in the FoE group than in the control group (FoE vs. control, 3.7% vs. 18.6%, P<0.001). The post-procedural use of analgesic and/or anti-emetic agents was less frequent in the FoE group (19.3% vs. 32.0%, P<0.001). On multiple logistic regression analysis after adjustment for age and sex, the use of a vitamin K antagonist (OR, 2.42; 95% CI: 1.18-4.99, P=0.02) and the FoE suture technique (OR, 0.17; 95% CI: 0.08-0.35, P<0.001) were independent predictors of rebleeding after CA. CONCLUSIONS: FoE suture technique effectively achieved femoral venous hemostasis after RFCA for AF. It reduced the risk of rebleeding, shortened bed rest duration, and relieved patient discomfort.

Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure.

Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure. However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined. Mitochondria are evolutionary endosymbionts derived from bacteria and contain DNA similar to bacterial DNA. Mitochondria damaged by external haemodynamic stress are degraded by the autophagy/lysosome system in cardiomyocytes. Here we show that mitochondrial DNA that escapes from autophagy cell-autonomously leads to Toll-like receptor (TLR) 9-mediated inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy. Cardiac-specific deletion of lysosomal deoxyribonuclease (DNase) II showed no cardiac phenotypes under baseline conditions, but increased mortality and caused severe myocarditis and dilated cardiomyopathy 10 days after treatment with pressure overload. Early in the pathogenesis, DNase II-deficient hearts showed infiltration of inflammatory cells and increased messenger RNA expression of inflammatory cytokines, with accumulation of mitochondrial DNA deposits in autolysosomes in the myocardium. Administration of inhibitory oligodeoxynucleotides against TLR9, which is known to be activated by bacterial DNA, or ablation of Tlr9 attenuated the development of cardiomyopathy in DNase II-deficient mice. Furthermore, Tlr9 ablation improved pressure overload-induced cardiac dysfunction and inflammation even in mice with wild-type Dnase2a alleles. These data provide new perspectives on the mechanism of genesis of chronic inflammation in failing hearts.

Automated Ablation Annotation Algorithm Reduces Re-conduction of Isolated Pulmonary Vein and Improves Outcome After Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Durable pulmonary vein isolation (PVI) is critical in reducing recurrence after radiofrequency catheter ablation for atrial fibrillation (AF). The VISITAG Module, an automatic annotation system that takes account of catheter stability and contact force (CF), might be useful in accomplishing this.Methods and Results:In 49 patients undergoing VISITAG-guided AF ablation (group A), we set the following automatic annotation criteria: catheter stability range of motion ≤1.5 mm, duration ≥5 s, CF ≥5 g, time ≥25% and tag diameter at 6 mm. We used ablation >20 s and force-time integral >150 gs at each site, then moved to the next site where a new tag appeared that overlapped with the former tag. Results and outcome were retrospectively compared for 42 consecutive patients undergoing CF-guided AF ablation without this algorithm (group B). Successful PVI at completion of the initial anatomical line was more frequent in group A than B (66.3% vs. 36.9%, P=0.0006) while spontaneous PV reconnection was less frequent (14.2% vs. 30.9%, P=0.0014) and procedure time was shorter (138±35 min vs. 180±44 min, P<0.001). One-year success rate off anti-arrhythmic drugs was higher in group A (91.8% vs. 69.1%, log rank P=0.0058). CONCLUSIONS: An automated annotation algorithm with an optimal setting reduced acute resumption of left atrium-PV conduction, shortened procedure time, and improved AF ablation outcome.

Rheb (Ras homologue enriched in brain)-dependent mammalian target of rapamycin complex 1 (mTORC1) activation becomes indispensable for cardiac hypertrophic growth after early postnatal period.

Cardiomyocytes proliferate during fetal life but lose their ability to proliferate soon after birth and further increases in cardiac mass are achieved through an increase in cell size or hypertrophy. Mammalian target of rapamycin complex 1 (mTORC1) is critical for cell growth and proliferation. Rheb (Ras homologue enriched in brain) is one of the most important upstream regulators of mTORC1. Here, we attempted to clarify the role of Rheb in the heart using cardiac-specific Rheb-deficient mice (Rheb(-/-)). Rheb(-/-) mice died from postnatal day 8 to 10. The heart-to-body weight ratio, an index of cardiomyocyte hypertrophy, in Rheb(-/-) was lower than that in the control (Rheb(+/+)) at postnatal day 8. The cell surface area of cardiomyocytes isolated from the mouse hearts increased from postnatal days 5 to 8 in Rheb(+/+) mice but not in Rheb(-/-) mice. Ultrastructural analysis indicated that sarcomere maturation was impaired in Rheb(-/-) hearts during the neonatal period. Rheb(-/-) hearts exhibited no difference in the phosphorylation level of S6 or 4E-BP1, downstream of mTORC1 at postnatal day 3 but showed attenuation at postnatal day 5 or 8 compared with the control. Polysome analysis revealed that the mRNA translation activity decreased in Rheb(-/-) hearts at postnatal day 8. Furthermore, ablation of eukaryotic initiation factor 4E-binding protein 1 in Rheb(-/-) mice improved mRNA translation, cardiac hypertrophic growth, sarcomere maturation, and survival. Thus, Rheb-dependent mTORC1 activation becomes essential for cardiomyocyte hypertrophic growth after early postnatal period.

Regional difference of optimal contact force to prevent acute pulmonary vein reconnection during radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Regional differences in optimal contact force (CF) to prevent acute pulmonary vein reconnection (APVR) during catheter ablation for atrial fibrillation (AF) remain unclear. OBJECTIVE: The purpose of this study was to evaluate regional difference in optimal CF during AF ablation. METHODS: This single-center observational study evaluated data from 57 consecutive drug-refractory AF patients (mean age, 62 ± 11 years; 43 males) who underwent initial pulmonary vein isolation (PVI) using the THERMOCOOL® SMARTTOUCH™ (Biosense Webster, Diamond Bar, CA, USA) catheter from June to August 2013. APVR was defined as the time-dependent reconnection >20 minutes after initial PVI and/or reconnection evoked by intravenous adenosine administration (20 mg). Point-by-point relationships between the reconnected points and their CF values were evaluated. RESULTS: Total 72 gaps causing APVR were observed. Of a total of 4,421 ablation points, 285 (6.4%) were associated with APVR. The average CF value of the points with APVR was significantly lower than that of those without (APVR vs. no APVR; 7.5 ± 6.7 g vs. 9.9 ± 8.4 g; P < 0.0001). The areas under the curve and optimal CF values differed between segments (range 0.593-0.761 and 10-22 g, respectively). The optimal CF value was highest in bottom of the right PV and posterosuperior right PV segments (22 g) and lowest in posteroinferior right PV segment (10 g). CONCLUSIONS: There was a regional difference in optimal CF values to prevent APVR, and the optimal CF value to prevent APVR with >95% probability was 10-22 g, depending on the individual peri-PV segments.

Quantitative analysis of fractionated electrogram area of left atrium during right atrial pacing as an indicator of left atrial electrical remodeling in patients with atrial fibrillation.

Background: The clinical significance of left atrial local electrogram fractionation after restoration of sinus rhythm in patients with atrial fibrillation (AF) has not been elucidated. Methods: We evaluated ultrahigh-resolution maps of the left atrium (LA) during RA pacing acquired after pulmonary vein isolation in 40 patients with AF. The association between low-voltage area (LVA, <0.5 mV), fractionated electrogram area (FEA, the highlighted area with LUMIPOINT™ Complex Activation), the interval from onset of LA activation to wavefront collision at the mitral isthmus (LA activation time), and wave propagation velocity (WPV) was evaluated quantitatively. Results: The total LVA, total FEA with ≥5.0 peaks or ≥7.0 peaks were 7.0 ± 7.9 cm2, 15.9 ± 12.9 cm2, and 5.2 ± 7.5 cm2, respectively. These areas were predominantly observed in the anteroseptal region. Total LVA, total FEA with ≥5.0 peaks, and total FEA with ≥5.0 peaks in the normal voltage area (NVA: ≥0.5 mV) correlated with LA activation time (R = 0.69, 0.75, and 0.71; each p < .0001). In the anterior wall, these areas correlated with regional mean WPV (R = -0.75, -0.83, and - 0.55; each p < .0001) and the extent of slow conduction area (SCA) with WPV <0.3 m/s (R = 0.89, 0.84, 0.33; p < .0001 for LVA and FEA, p < .05 for FEA located in NVA). The anterior wall FEA with ≥7.0 peaks and that in the NVA showed a better correlation in predicting anterior wall SCA (R = 0.92 and 0.86, each p < .0001). Conclusion: Quantitative analysis of FEA together with LVA may facilitate the assessment of LA electrical remodeling.