Search

Background Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery and results in increased health-care utilization. This study identified new transthoracic echocardiographic predictors of POAF using an index of the total atrial conduction time derived on tissue Doppler imaging (PA-TDI duration) in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Methods and results A total of 88 patients undergoing isolated OPCAB were enrolled. They were examined preoperatively on transthoracic echocardiography with tissue Doppler evaluations and monitored postoperatively with continuous electrocardiographic telemetry for 7 days. POAF occurred in 35 patients (39.8%). Patients with POAF had a significantly longer duration of hospital stay than those without (44.9±6.2 vs. 37.3±3.3 days, P=0.04). Multivariate analysis showed that PA-TDI duration (odds ratio [OR], 1.11; 95% confidence interval [CI]: 1.06-1.16; P=0.0001) and left atrial volume index (LAVI; OR, 1.11; 95% CI: 1.02-1.20; P=0.01) were independent predictors of POAF. Moreover, PA-TDI duration was more reliable, given an area under the receiver operating characteristic curve of 0.85 (sensitivity, 74.3%; specificity, 86.8%). Conclusions PA-TDI duration was an independent predictor of POAF following OPCAB. Awareness of risk of POAF may lead to the prevention of POAF, a rapid response to POAF, shortened hospital stay, and improved prognosis.

We previously demonstrated that 5-HT stimulants, including selective serotonin reuptake inhibitors (SSRIs), potentiated antipsychotic-induced extrapyramidal symptoms (EPS) by stimulating 5-HT2A/2C, 5-HT3 and 5-HT6 receptors. Here, we studied the effects of the 5-HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino) tetralin ((±)-8-OH-DPAT) on the fluoxetine enhancement of EPS (i.e., bradykinesia and catalepsy) to determine if the 5-HT1A agonist can counteract the serotonergic potentiation of EPS. Fluoxetine did not induce EPS signs by itself, but significantly potentiated haloperidol-induced bradykinesia in mice. (±)-8-OH-DPAT (0.1-1mg/kg, i.p.) significantly attenuated the fluoxetine enhancement of haloperidol-induced bradykinesia in a dose-dependent manner. A selective 5-HT1A antagonist (s)-WAY-100135 completely reversed the anti-EPS action of (±)-8-OH-DPAT. Microinjection studies using rats revealed that local application of (±)-8-OH-DPAT into the dorsolateral striatum or the motor cortex significantly diminished fluoxetine-enhanced catalepsy. In contrast, (±)-8-OH-DPAT injected into the medial raphe nucleus failed to affect EPS induction. The present results illustrate that 5-HT1A agonist can alleviate the SSRI enhancement of EPS by activating postsynaptic 5-HT1A receptors in the striatum and cerebral cortex.

Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67–5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A I334V, VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A I334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A I334V. Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A I334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A I334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA., Author Summary Unexplained cardiac arrest with documented ventricular fibrillation (UCA) is defined as spontaneous ventricular fibrillation (VF) that is not associated with known structural or electrical heart diseases and is one of the major causes of sudden cardiac death. Identification of the genes responsible for UCA may further increase our understanding of mechanisms of UCA and facilitate more accurate diagnosis and preventive treatment, especially in asymptomatic disease-carrying relatives of the patient. However, molecular mechanisms of UCA have not been fully clarified due to the high mortality rate and difficulty of diagnosis. In this study, UCA patients are shown to have a high incidence of a polymorphism in the Semaphorin 3A gene (rs138694505, SEMA3A I334V). The result confirms previous reports that the abnormal sympathetic innervation is a trigger of UCA because SEMA3A is crucial for the establishment of normal innervation patterns in the heart. Furthermore, experimental data presented here indicate that SEMA3A I334V disrupts the SEMA3A function and impairs appropriate innervation patterning. Finally, the study suggests that SEMA3A I334V is a risk factor for human UCA and contributes to the etiology of UCA.

TLR2 expression is enhanced in MS and EAE, but its role in these diseases is controversial. In adoptive transfer EAE, exogenous TLR ligands are not administered yet TLR2-deficient mice have been reported to develop attenuated disease. Despite this evidence for a disease-promoting function of TLR2, others have shown the opposite, i.e. that administration of TLR2 ligands can inhibit EAE in WT mice. To understand this paradox we tested the postulate that although TLR2 signaling may be EAE-promoting, repeated TLR2 ligand administration can lead to diminished TLR2 responsiveness (tolerance) and attenuated disease. To establish our approach, we administered Pam2Cys to SJL/J mice for 5 days and induced TLR2 tolerance that persisted for 4–5 days, reflected in decreased serum TNFα in response to a second TLR2 ligand (p In sum, we have used TLR tolerance as a novel probe to identify a narrow kinetic window in which TLR2 is required for EAE. Additionally, we have demonstrated the potential use of TLR tolerance as a new therapeutic approach in EAE and MS. Ongoing studies will characterize the relevant TLR2-expressing cells in EAE and the potential role of the microbiome in inducing homeostatic TLR tolerance that regulates autoimmunity.

The PD-L1/PD-1 pathway is a critical regulator of T cell responses that has become a significant focus in cancer immunotherapy. Cbl-b is an E3 ubiquitin ligase that regulates many aspects of T cell activation. In humans, polymorphisms in the CBLB gene are associated with autoimmunity. Cbl-b deficient (Cbl-b−/−) mice demonstrate spontaneous autoimmunity and enhanced anti-tumor T cell responses. Thus, there is now great interest in manipulating Cbl-b to enhance anti-tumor T cell responses. We now report that, in contrast to WT T cells, in vitro TCR-stimulated proliferative responses of Cbl-b−/− CD4+ and CD8+ T cells are not suppressed by a recombinant PD-L1 fusion protein (PD-L1 Ig) (% suppression in CD4+: WT 40%, Cbl-b 0%, p In sum, we report for the first time that Cbl-b−/− T cells are resistant in vitro and in vivo to suppression by PD-L1/PD-1. Our finding of Cbl-b−/− T cell resistance to PD-L1/PD-1-mediated inhibition broadens our understanding of Cbl-b’s role in autoimmunity and suggests a new mechanism by which manipulation of Cbl-b function may lead to enhanced anti-tumor T cell responses.

Sinus node dysfunction (SND) occasionally coexists with long-standing atrial fibrillation (AF) but is unidentifiable during AF. We aimed to identify the predictors of underlying SND when deciding the indications for long-standing persistent AF ablation.We included 105 patients undergoing ablation of long-standing persistent AF to assess the frequency of a permanent pacemaker implantation (PMI) for SND that manifested after sinus conversion and to determine the relationship between the corrected sinus node recovery time (CSNRT) and other clinical parameters obtained before the ablation including the atrial fibrillatory cycle length (AFCL).We identified 7 patients (7%) requiring a PMI for SND after AF termination. The patients with a PMI were nearly all females (6/7) and had a significantly longer CSNRT (1197 ± 647 vs 612 ± 349 milliseconds; P = .0046) and more prolonged AFCL (179 ± 19 vs 153 ± 22 milliseconds; P = .0028) than those without. The age (r = 0.26; P = .011), female sex (r = 0.25; P = .012), hypertension (r = 0.22; P = .038), and AFCL (r = 0.4; P.0001) were significantly correlated with the CSNRT. A stepwise multivariate linear regression analysis including these parameters revealed that the AFCL was the only independent determinant of the CSNRT (β = 0.38; P = .0012). A receiver operating characteristic curve identified an AFCL of more than 162 milliseconds as the optimal cutoff value for predicting SND requiring a PMI (area under the curve, 0.84; sensitivity, 86%; specificity, 74%; P = .0066).A prolonged AFCL was significantly associated with SND. Thus, assessing the AFCL in the patients with long-standing persistent AF may be helpful for the risk stratification of underlying SND.

Sinus node dysfunction (SND) occasionally coexists with atrial flutter (AFL). However, the identification of SND during AFL is difficult. We investigated whether we could predict underlying SND in patients with persistent AFL using the flutter cycle length (FCL).We retrospectively studied 211 successfully ablated patients with persistent cavotricuspid isthmus (CTI)-dependent AFL and measured the FCL before the ablation and corrected sinus node recovery time (CSNRT) after the ablation. Twenty-four patients (11%) required a permanent pacemaker implantation (PMI) for significant SND after AFL termination and had a longer FCL (295 ± 37 vs. 236 ± 34 ms; P0.0001) and greater CSNRT (1727 ± 1014 vs. 603 ± 733 ms; P0.0001) than those not requiring a PMI. A receiver-operating characteristic curve identified an FCL of273 ms as the optimal cut-off value for predicting SND requiring a PMI (area under the curve 0.91; sensitivity, 83% and specificity, 89%; P0.0001). Multiple linear and logistic regression analyses revealed that the left ventricular ejection fraction (LVEF) (β = -0.2; P= 0.0016) and FCL (β = 0.46; P0.0001) were independently associated with the CSNRT, and that females [odds ratio (OR), 2.43; 95% confidence interval (CI), 1.32-4.62; P= 0.0046], an LVEF50% (OR, 2.10; 95% CI, 1.20-3.87; P= 0.012), and an FCL of273 ms (OR, 5.34; 95% CI, 3.08-10.08; P0.0001) were independent predictors of SND requiring a PMI.Although this study was based on a review of a database, the results suggest that assessing the FCL in patients with persistent CTI-dependent AFL could be helpful in the risk stratification of underlying SND.

Tyrosinase inhibitory activity-guided fractionation of the bark of Peltophorum dasyrachis (yellow batai) led to the isolation of the six active compounds which were characterised as six flavonoids: apigenin (1), (+)-2,3-trans-dihydrokaempferol (2), (+)-2,3-trans-dihydrokaempferol-3-O-α-L-rhamnoside (3), (+)-4',7-dimethoxy-2,3-trans-dihydroquercetin (4), (+)-2,3-trans-dihydroquercetin (5) and (-)-2,3-trans-dihydroquercetin-3-O-α-L-rhamnoside (6). All compounds were isolated for the first time from the bark of P. dasyrachis. Moreover, all compounds were evaluated for tyrosinase activities towards L-DOPA as the substrate. We observed that compounds 2 and 5 showed potent inhibitory effects (IC₅₀ values were 126 ± 3.2 and 210 ± 5.8 µM, respectively). In general, for flavonoids the 3',4'-dihydroxy group's substituent is a more potent inhibitor than the 4'-hydroxy group substituent, i.e. quercetin > kaempferol. Interestingly, our result in the oxidation of L-DOPA showed that the 4'-hydroxy group substituent (compound 2) is a more potent inhibitor than the 3',4'-dihydroxy group substituent (compound 5). This result showed a new relationship between tyrosinase inhibitory activities and flavonoids. The kinetic analyses by Lineweaver-Burk plots showed that both the compounds 2 and 5 behaved as competitive inhibitors of L-DOPA oxidation.

Biotransformation studies conducted on (+)-(S)-ar-turmerone (1) and (+)-(S)-dihydro-ar-turmerone (2) by the fungus Aspergillus niger have revealed that 1 was metabolized to give four oxidized metabolites, (+)-(7S)-hydroxydehydro-ar-todomatuic acid (3), (+)-(7S,10E)-12-hydroxydehydro-ar-todomatuic acid (4), (+)-(7S,10E)-7,12-dihydroxydehydro-ar-todomatuic acid (5), and (+)-(7S)-15-carboxy-9,13-epoxy-7-hydroxy-9,13-dehydro-ar-curcumene (6), and (+)-(S)-dihydro-ar-turmerone (2) was metabolized to (+)-7,11-dihydroxy-ar-todomatuic acid (7). Metabolites 3−7 were characterized using spectroscopic techniques. Metabolites 3−7 inhibited acetylcholinesterase (AChE) although less so than the parent substrates.

In previous studies, the minimal luminal diameter (MLD) of lesions treated with a bare metal stent (BMS) was shown to improve from 6 months to 3 years. However, the long-term response to a sirolimus-eluting stent (SES) implantation remains unclear.To evaluate 6-month, 12-month and 3-year outcomes, clinical and angiographic follow-up data were analyzed for 367 consecutive patients (506 de novo lesions) who underwent successful SES implantation compared to follow-up data for 617 consecutive patients (802 de novo lesions) who underwent BMS implantation. Clinical follow-up information was obtained for 363 SES-treated patients (98.9%) and 581 BMS-treated patients (94.2%) at 1 year, and 334 SES-treated patients (91.0%) and 566 BMS-treated patients (91.7%) at 3 years. At 3 years, there were no significant differences in the cumulative cardiac death and myocardial infarction. Target lesion revascularization (TLR) rates were significantly higher in BMS-treated patients than in SES-treated patients. In BMS-treated patients, most TLR was performed within 450 days, however, after 450 days, the TLR rate was significantly lower than that for the SES-treated patients. In quantitative coronary angiographic data, among lesions that required no revascularization at the initial 12-month follow up, MLD increased significantly from the 12-month to the 3-year follow-up angiography in BMS-treated lesions. However, MLD decreased significantly in SES-treated lesions.From a 12-month follow-up to a 3-year follow-up, stenosis in BMS-treated lesions regressed, but stenosis in SES-treated lesions progressed. And late TLR was more frequently required in the SES-treated patients.

The role of the microbiome in multiple sclerosis (MS) remains unknown. We have identified a novel commensal bacteria-produced lipodipeptide, Lipid 654 (L654), which functions as a toll-like receptor 2 agonist. We reported that L654 can be recovered in healthy human serum and that levels are significantly lower in patients with MS. The purpose of this study was to understand the functional relevance of the decreased serum L654 level in MS by determining: 1) if L654 attenuates clinical disease in a transfer model of EAE, and 2) the mechanism by which L654 mediates this attenuation. L654 administration significantly attenuated clinical disease severity in an adoptive transfer model of EAE in SJL/J mice (p < 0.0001). Cellular analysis of mononuclear cells in the spinal cord at day 18 showed a significant decrease in total cell number (p = 0.02) as well as a decrease in percentage of IL-17 producing, IFNγ producing and IL-17/IFNγ double-producing CD4+ T cells in mice administered L654. At day 11, we found a decrease in total mononuclear cell number and an increase in percentage of CD39+ Tregs and IL-10 producing CD11b+ cells in mice administered L654. These results suggest that L654, normally present in human serum but at significantly lower levels in MS serum, has the ability to mediate an immunoregulatory and disease inhibitory effect on CNS autoimmunity. L654 may thus have a role both in the abnormal immunoregulation in MS and as a potential therapeutic in this disease.

FTY720 is a sphingosine-1-phosphate receptor 1 (S1P1) modulator used to treat Multiple Sclerosis (MS). While FTY720 is postulated to mediate its effect by enhancing T cell S1P1 internalization and degradation, the mechanisms underlying the therapeutic effect of FTY720 in MS are not fully understood. To further clarify the functional effects of FTY720 we utilized Cbl-b-deficient (Cbl-b-/-) mice. Cbl-b is an E3 ubiquitin ligase that regulates the PI3K-Akt pathway in T cells and its absence leads to resistance to regulatory T cells (Tregs) and multi-organ autoimmunity in mice. Given that MS has been associated with both SNPs in the CBLB gene and resistance to Tregs, Cbl-b-/- mice represent an important model for studying MS. We now report that Cbl-b-/- T cells demonstrate multiple functional abnormalities in S1P1. These include significantly less lymphopenia induced by the S1P lyase inhibitor, THI, (Cbl-b-/- blood CD4+ T cells decreased 19% vs 59% in wild type (WT) at 48 hrs), suggesting abnormal regulation of Cbl-b-/- T cell S1P1 in response to the endogenous ligand S1P. Paradoxically, Cbl-b-/- T cells demonstrate enhanced lymphopenia induced by the therapeutic agent FTY720 (Cbl-b-/- blood CD4+ T cells decreased 51% vs 26% in WT at 120 hrs). These results for the first time identify a complex role for Cbl-b in regulating expression and turnover of T cell S1P1 and suggest that SNPs in the CBLB gene may associate with a differential response to FTY720 in MS patients.

Multiple sclerosis (MS) is an autoimmune disease of unknown etiology. Infectious agents have been suggested to have a role as environmental factors in MS, but this concept remains controversial. Recently, gastrointestinal commensal bacteria have been implicated in the pathogenesis of autoimmune diseases, but mechanisms underlying the relationship of human systemic autoimmunity with the commensal microbiome have yet to be identified. Consistent with the lack of understanding of pathogenic mechanisms and relevant environmental factors in MS, no blood biomarkers have been identified that distinguish MS patients from healthy individuals. We recently identified a unique gastrointestinal and oral bacteria-derived lipodipeptide, Lipid 654, which is produced by commensal bacteria and functions as a human and mouse Toll-like receptor 2 ligand. Using multiple-reaction-monitoring mass spectrometry, a critical approach in targeted lipidomics, we now report that Lipid 654 can be recovered in the serum of healthy individuals. Most interestingly, we find that Lipid 654 is expressed at significantly lower levels in the serum of patients with MS compared with both healthy individuals and patients with Alzheimer's disease. These results thus identify for the first time a potential mechanism relating the gastrointestinal and oral commensal microbiome to a human systemic autoimmune disease. In addition, these results also identify a potential etiologic environmental factor and novel clinically relevant serum biomarker for MS.

Introduction Vaccines based on replicating viral vectors that express foreign antigens can generate superior durable antibody and memory CD8 T cell responses compared to inactivated virus or recombinant protein, with the added benefit of potential needle-free intranasal administration. Despite these significant advantages, safety concerns related to viral vectors as vaccine platforms can be an issue with this approach. Replicating viral vectors are perceived as less safe alternatives compared to other immunization modalities, especially in the context of intranasal administration, where the potential exists for systemic virus spread from the lung. The type III interferons (IL-29, IL-28A, IL-28B; also known as IFN-lambda1, 2, and 3) play a critical role in protecting epithelial cells in the lung and gut from virus infection, and can also stimulate adaptive immunity. We therefore examined the ability of this cytokine family to improve the safety and efficacy of a viral vector by limiting its systemic spread and vector-associated pathological effects after intranasal delivery. Methods Vesicular stomatitis virus (VSV) based vectors are promising candidates for use as vaccines and oncolytic agents. We generated recombinant VSV vectors expressing mouse IL-28A either from the fifth position or the more highly expressing first position of the viral genome, and measured virus replication in cell culture and mice. Results We found that IL-28A is properly expressed, secreted, and active when produced by VSV-infected cells. In cell culture, expression of IL-28A from VSV attenuated virus replication in type III IFN-sensitive cells, but not in type III IFN-resistant cells. Following intranasal inoculation in mice, spread of the VSV.IL28A vector from the lung to the lymph nodes, spleen, blood, liver, and brain was significantly reduced compared to recombinant wild-type VSV. Despite this attenuation, the VSV.mIL28A vector generated virus-specific CD8 T cell and antibody responses in mice that were comparable to wild-type VSV. Conclusion These studies demonstrate the ability of the type III interferon cytokine family to improve the safety and efficacy of a clinically promising viral vaccine vector. These results may potentially also inform the enhancement of VSV oncolytic activity by increasing selectivity of the virus for type III IFN-resistant tumor cells.

Purpose: Myocardial thickness is particularly thick at the ridge between the left pulmonary vein (PV) and the left atrial appendage (LAA) by dissection. We investigated whether the atrial fibrillation (AF) ablation outcome was influenced by altering ablation strategies according to the thickness of the PV-LAA ridge using preprocedural multidetector computed tomography (MDCT). Methods: Patients with AF scheduled for extensive encircling circumferential pulmonary vein isolation (EEPVI) (110 pts) were divided into two groups. In the nonmodulation group (32 pts), EEPVI lines were created using a 3.5-mm tip irrigated catheter at a maximum power of 30 W for 15–20 s at each site. In the modulation group (78 pts), ablation was extended (30–40 s) at the PV-LAA ridge if its thickness was >4.0 mm on MDCT. Results: In the modulation group, extended ablation at the PV-LAA ridge was observed in 37 pts. During 25±9 months of follow-up, the recurrence was significantly less in the modulation group (10% vs. 28%, p=0.018). Logistic regression analysis demonstrated that modifications in the ablation time and LA volume index were independent predictors of arrhythmia-free recovery after ablation. Conclusion: Recurrence following EEPVI could be reduced by modifications in the ablation time at the PV-LAA ridge.

Background: Indication of ablation has been expanded to include chronic atrial fibrillation (CAF) for enabling high degree of sinus rhythm maintenance. We have encountered patients undergoing pacemaker implantation, in whom sick sinus syndrome became clinically evident after ablation. The study aims to investigate whether underling sinus node dysfunction (SND) during CAF can be predicted before deciding the indication for ablation. Methods and Results: Sixty consecutive patients with CAF who underwent ablation between January to December 2010 were enrolled in the study. Nocturnal polysomnography as well as echocardiography was performed for all patients before ablation. We used the double Lasso catheter and electro anatomical mapping guided extensive encircling pulmonary vein isolation (EEPVI). We performed electrophysiological studies after EEPVI, and SND was defined as corrected SN recovery time of ≥550 ms. SND was detected in 26 (43%) patients (SND group); the other patients showed normal sinus node function (NSN group). The apnea/hypopnea index (AHI) was significantly greater in the SND group than in the NSN group (25.7±13 vs 15.8±10, P=0.0022). On multivariate analysis, sleep apnea syndrome (SAS) was an independent predictor of SND after ablation for CAF. Conclusion: This study suggested that underlying SND in CAF patients can be predicted by evaluating SAS before ablation.

Music and other sounds have been played to provide a pleasant sound environment for workers in a factory. In terms of "Sound Perspicuity" this case study was conducted to assess audibility of spatial sounds, which were adjusted in level without increasing total sound pressure level (SPL) at the workstation. Furthermore, the added sounds were not audible at other workstations. Three speaker systems, including line‐array speaker (60 cm in length), were used for the case study. The ratio of added sound (Signal) to factory noise (Noise) was analyzed at every measuring point on a grid of 50 cm by 50 cm. Audibility listening tests were performed for the added sounds, such as natural‐environment sounds and musical instrument tones, with Signal to Noise ratios analyzed from three types of speaker. As a result, a sound is recognized as "Kiwadachi" by a Japanese adjective word even when the factory noise has higher levels than the added sounds. Audibility test results for each added sound are discussed with differe...

Recently, speech privacy to avoid oral information leakage in healthcare facilities has become an important issue. This study investigated effectiveness of sound masking system in regard to masking efficiency, annoyance and its influence on speech conversation for medical examination rooms in an experimental approach. Considering actual application, two adjacent medical examination rooms partitioned by a low sound insulation wall in a typical healthcare facility were selected as an experimental field and sound masking system was temporally installed. In the rooms, acoustic environment was measured and reproduced in an anechoic room with a 3‐D sound field simulation system using a 6‐ch sound recording/reproduction technique. In the simulated acoustic condition, subjective tests were designed to quantify the masking efficiency and annoyance caused by the masking sound. The annoyance test was conducted in listening condition (with high attention to the sound) and in talking condition (with low attention). As a result, mixed maskers composed by water stream, synthesized speech signals, and steady state noise showed high performance in both aspect of masking efficiency and annoyance.

Background Myocardial thickness is particularly thick at the ridge between the left pulmonary vein (PV) and the left atrial appendage (LAA) by dissection. We investigated whether atrial fibrillation (AF) ablation outcome was influenced by altering ablation strategies according to the thickness of the PV–LAA ridge using preprocedural multidetector computed tomography (MDCT). Methods and results Patients with AF scheduled for extensive encircling circumferential pulmonary vein isolation (EEPVI) (110 patients) were divided into 2 groups. In the nonmodulation group (32 patients), EEPVI lines were created using a 3.5-mm tip irrigated catheter at a maximum power of 30 W for 20–30 s at each site. In the modulation group (78 patients), ablation was extended (40–60 s) at the PV–LAA ridge if its thickness was >4.0 mm on MDCT examination. Extended ablation at the PV–LAA ridge was noted in 37 patients in the modulation group. During 25 ± 9 months of follow-up, recurrence was significantly less in the modulation group than in the nonmodulation group (10% vs. 28%; p = 0.018). Logistic regression analysis showed that modifications in the ablation time and left atrium volume index were independent predictors of arrhythmia-free recovery after ablation. Conclusions Recurrence following EEPVI could be reduced by modifications in the ablation time at the PV–LAA ridge.