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BACKGROUND Atrial fibrillation (AF) ablation with minimally interrupted direct oral anticoagulants (DOACs) may raise a concern about their remaining activity. We tested the residual activity of four different DOACs and its impact on intraprocedural heparinization in patients undergoing AF ablation. METHODS We measured the anti-factor Χa activity for rivaroxaban, apixaban, and edoxaban, and serum DOAC concentration for rivaroxaban, apixaban, and dabigatran, 24 hours after the last intake in patients undergoing AF ablation treated with standard or reduced doses of DOACs. The heparin requirement during the procedure was also measured. RESULTS We enrolled 34 patients with rivaroxaban, 35 with apixaban, 32 with edoxaban, and 31 with dabigatran, and among them, 30 were treated with reduced doses. The anti-factor Χa activity was the highest in the apixaban group among the patients with standard doses. The DOAC concentration was paradoxically lower in patients with standard doses than in those with reduced doses among the patients with rivaroxaban (34.3 ± 19.8 vs 56.6 ± 7.7 ng/mL; P = .01) and dabigatran (12.6 ± 10.6 vs 23.4 ± 14.7 ng/mL; P = .03). The total heparin requirement per body surface area had significant correlations with the anti-factor Χa activity (r = -.36) and DOAC concentration (r = -.32). Two different multiple linear regression models (adjusted R2 = 0.56 and 0.6, respectively) revealed that the anti-factor Χa activity (β = -.28; P = .002) and DOAC concentration (β = -.38; P

BACKGROUND A diagnosis of silent paroxysmal atrial fibrillation (AF) is highly challenging due to its asymptomatic and intermittent nature. The goal of the present study was to clarify its asymptomaticity with the use of a comprehensive electrophysiological approach. METHODS We prospectively compared (a) 24-hour Holter monitoring data, (b) invasive cardiac electrophysiological properties, (c) AF inducibility, and (d) outcome of radiofrequency catheter ablation between patients with symptomatic paroxysmal AF and those with silent paroxysmal AF, defined as transient asymptomatic AF detected by chance. RESULTS Patients with silent paroxysmal AF (N = 57) were more likely than patients with symptomatic paroxysmal AF (N = 282) to be male (75.4% vs 56.7%; P = .009), and to have a previous stroke (17.5% vs 6.7%; P = .008), more prolonged atrio-His interval (114.9 ± 29.1 vs 105.5 ± 24.1 ms; P = .01), longer atrioventricular nodal effective refractory period (352.3 ± 103 vs 318.2 ± 77.2 ms; P = .007), slower Wenckebach cycle length (488.5 ± 83.9 vs 443.3 ± 74.9 ms; P

There is a concern about worsening anemia after atrial fibrillation (AF) ablation in anemic patients. We aimed to clarify whether or not patients with anemia who are on an oral anticoagulant therapy are more likely to lose blood after AF ablation.We studied AF patients in 3 cardiovascular centers who skipped a single dose of a direct oral anticoagulant prior to the ablation, and compared the drop in the hemoglobin level 24 hours after the procedure and bleeding complications between the patients with and without preexisting anemia.We identified 183 (15.7%) patients with anemia at baseline out of 1163 patients. The reduction in the hemoglobin level (-0.39±0.71 vs. -0.93±0.9 g/dL; p0.001) was smaller in the anemic than non-anemic patients. A fall in the hemoglobin level of ≥2 g/dL, which is a guideline-defined significant hemoglobin drop, was less common in anemic patients (1.6% vs. 11.3%; p0.001). A female gender [odds ratio (OR) 1.62, confidence interval (CI) 1.07-2.45; p=0.02], persistent or long-standing persistent versus paroxysmal AF (OR 1.67, CI 1.13-2.49; p=0.01), ORBIT score ≥3 (OR 3.5, CI 1.34-8.94; p=0.01), and preexisting anemia (OR 0.02, CI 0.004-0.14; p0.001) were independently associated with the fall in the hemoglobin level of ≥2 g/dL. No difference was noted in the rate of major bleeding complications (1.6% vs. 1.2%; p=0.72).Paradoxically, patients with preexisting anemia may be less likely to lose blood following AF ablation.

Background: There is a concern about worsening of anemia after atrial fibrillation (AF) ablation in anemic patients. We aimed to clarify whether or not patients with anemia who are on an oral anticoagulant therapy are more likely to lose blood after AF ablation. Methods: We studied AF patients in 3 cardiovascular centers who skipped a single dose of direct oral anticoagulants prior to the ablation, and compared the drop in the hemoglobin level 24 hours after the procedure and bleeding complications between the patients with and without preexisting anemia. Results: We identified 183 (15.7%) patients with anemia at baseline out of 1163 patients. The reduction in the hemoglobin level (-0.39±0.71 vs. -0.93±0.9 g/dL; P

Genome-wide association studies have reported a strong association of the single nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial fibrillation (AF), but phenotype alterations conferred by this SNP have not been described. We genotyped SNP rs6817105 and examined the relationships among rs6817105 genotype, clinical characteristics, echocardiographic parameters, and electrophysiological parameters in 574 AF patients and 1,554 non-AF controls. Further, multiple microRNAs (miRNAs) are reported to be involved in atrial remodeling and AF pathogenesis, so we investigated relationships between rs6817105 genotype and serum concentrations of 2555 miRNAs. The rs6817105 minor allele frequency was significantly higher in AF patients than non-AF controls (66% vs. 47%, odds ratio 2.12, p = 4.9 × 10−26). Corrected sinus node recovery time (CSRT) was longer and left atrial volume index (LAVI) was larger in AF patients with the rs6817105 minor allele than patient non-carriers (CSRT: CC 557 ± 315 ms, CT 486 ± 273 ms, TT 447 ± 234 ms, p = 0.001; LAVI: CC 43.6 ± 12.1, CT 42.4 ± 13.6, TT 39.8 ± 11.6, p = 0.030). There were no significant differences between rs6817105 genotype and the serum concentrations of miRNAs. These findings strongly implicate rs6817105 minor allele in sinus node dysfunction and left atrial enlargement.

1 Background: Cryoballoon (CB) applications to pulmonary veins (PVs) can cause stenosis just as radiofrequency (RF) energy deliveries. The goal of the present study was to clarify whether or not there was any difference in the extent of acute or chronic PV narrowing after PV isolation between the two different energy sources. 2 Methods: Consecutive patients with paroxysmal atrial fibrillation who were scheduled to undergo a PV isolation were randomized 1:1 to receive CB or RF ablation. The endpoints were any acute PV narrowing assessed with the use of intracardiac ultrasound during the procedure and PV stenosis measured with cardiac computed tomography at the 3‐month follow‐up. 3 Results: An acute reduction in the luminal area of the left superior PV (mean ± standard deviation, –6.8 ± 8.7 vs –19.9 ± 14.7%; P < 0.001) and left inferior PV (–5.1 ± 20.2 vs –15.3 ± 11.6%; P = 0.03) was significantly smaller in the CB arm (N = 25) than the RF arm (N = 25). There was no difference in the extent of PV stenosis 3 months after the ablation between the arms (0–25% stenosis, 90% vs 88%, 25–50% stenosis, 10% vs 12%, >50% stenosis, both 0%; P = 0.82). A greater acute PV narrowing was likely to lead to chronic stenosis in the RF arm (P = 0.004). 4 Conclusions: CB ablation may reduce the acute narrowing of the left‐sided PVs as compared to RF ablation., ファイル公開：2019-04-01

Objectives We aimed to test a novel stent-less revascularization strategy using a combination of excimer laser coronary angioplasty (ELCA) and drug-coated balloon (DCB) for patients with acute coronary syndrome (ACS). Background Percutaneous coronary intervention with drug eluting stents is a standard invasive treatment for ACS. Some unsolved issues however remain, such as stent thrombosis and bleeding risks associated with dual antiplatelet therapy. Methods Consecutive ACS patients were planned to receive either a DCB application following ELCA without a stent implantation or conventional revascularization with a coronary stent. The endpoints were (i) major cardiac adverse events (MACEs), defined as the composite of cardiac death, myocardial infarctions, and target lesion revascularization; (ii) target vessel revascularization (TVR); and (iii) angiographic outcome. Results Since a greater than expected number of patients allocated to the stent-less treatment arm eventually received a bailout stenting, the following 3 as-treated groups were compared; DCB with ELCA group (N = 60), Stent with ELCA group (N = 23), and Stent without ELCA group (N = 85). During a mean follow-up period of 420 ± 137 days, and with angiographic 6- and 12-month-follow-up rates of 96.7%, 87%, and 81.2%, and 50%, 65.2%, and 45.9%, respectively, the MACE rate did not differ across the groups (10%, 4.3%, and 3.5%; P = 0.22) while an incidence of TVR was more common (15%, 0, and 4.7%; P = 0.02) and the diameter stenosis at 6-months of follow-up was greater (25.7 ± 18.2, 14.9 ± 13.1 and 16.2 ± 15.4%; P = 0.002) in the DCB with ELCA group. Conclusions The stent-less revascularization strategy with DCB and ELCA was associated with a higher occurrence of restenosis in ACS patients.

Background Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) refractory to medical therapy remains controversial in patients with hypertrophic cardiomyopathy (HCM); the acute effects on the direct left atrial (LA) pressure are not completely understood. Methods We consecutively studied patients with HCM (n=15) and without HCM (NHCM, n=106) who underwent extensive encircling pulmonary vein isolation for drug-refractory AF. We compared clinical parameters, echocardiographic parameters, electrophysiological parameters, LA pressures using hemodynamic catheterization and recurrence rate in both groups. Results The LA volume index was significantly higher (51.9±13.6 mL/m2 vs. 41.6±12.7 mL/m2, p=0.02) in the HCM group than the NHCM group. The pre-ablation mean LA pressure was significantly higher in the HCM group than the NHCM group. Among the AF patients, the mean LA pressure decreased more significantly in the HCM group than the NHCM group (post-ablation minus pre-ablation pressures: 4.2±3.7 mmHg vs. 0.9±4.1 mmHg, p=0.03). The early recurrence rate (within 30 days after ablation) tended to be higher in the HCM group than the NHCM group (20% vs. 5.7%, p=0.08), but the rates of late recurrences (>30 days after ablation) were similar (13.3% vs. 7.6%, p=0.83). Discontinuation of antiarrhythmic drugs occurred at rates of 13% and 62% in the HCM and NHCM groups, respectively (p Conclusions The LA pressure in the HCM group decreased immediately after AF RFCA. Patients with HCM and drug-refractory AF may benefit from RFCA.

Atrial fibrillation (AF) ablation with minimally interrupted direct oral anticoagulants (DOACs) predominates, possibly raising concern about their remaining activity during the procedure. We aimed to examine residual activities of 4 different DOACs.The serum DOAC concentration and anti-factor Χa activity were measured 3 and 24 h after the last intake in patients undergoing AF ablation who were treated with rivaroxaban, apixaban, edoxaban, or dabigatran.The reduction in the apixaban concentration between the 2 blood sampling time points (N = 32, mean ± SD, -67.7 ± 14.8% [231.6 ± 93.1 to 71.9 ± 31.8 ng/mL]) was smaller than that for rivaroxaban (N = 28, -83.6 ± 10.9% [234.2 ± 96.6 to 34.3 ± 19.8 ng/mL]; P 0.001) and dabigatran (N = 20, -90.7 ± 7.3% [135.3 ± 68.3 to 12.6 ± 10.6 ng/mL]; P 0.001), with its greatest value measured 24 h after the last intake in the apixaban group. The decrease in the anti-factor Χa activity was also smaller in the patients with apixaban (-73.8 ± 12.7%) than with rivaroxaban (-87.9 ± 7.9%; P 0.001) and edoxaban (N = 22, -81.9 ± 15.2%; P = 0.049), and its remaining activity 24 h after the last dose was the highest in the apixaban group. A serum DOAC concentration measured 24 h after the last dose of30 ng/mL was seen in 41 (51.3%) patients with rivaroxaban, apixaban, or dabigatran, and it was independently associated with apixaban versus rivaroxaban (odds ratio 5.0; P = 0.01) and apixaban versus dabigatran (odds ratio 74.0; P 0.001).The pattern of drug elimination from blood may vary depending on DOACs, and their residual activity may not be negligible even 24 h after the last intake.

Among heart failure patients diagnosed as having exertional oscillatory ventilation (OV), some present with OV at rest that persists during exercise, and others develop OV only after the onset of exercise during cardiopulmonary exercise (CPX) testing. We tested whether or not there was any difference in the prognostic significance between the two abnormal breathing patterns.Patients with New York Heart Association class III-heart failure were categorized into the following 3 groups according to their ventilation pattern during the CPX: patients with an OV pattern at rest that persisted for ≥60% of the exercise test at an amplitude of ≥15% of the average resting value (group 1), patients with the same abnormal ventilatory pattern as group 1 that was observed only during exercise (group 2), and patients without any OV (group 3). The patients were followed-up for at least 2 years to assess the composite outcome of cardiac death or hospitalization for worsening heart failure.The occurrence of the composite outcome differed significantly across the groups with its highest occurrence in group 1 (21/29 [72.4%], 15/38 [39.5%] and 48/167 [28.7%]; log-rank P 0.001). In multivariate hazard analyses, an N-terminal pro-brain natriuretic peptide of900 pg/mL (hazard ratio [HR] = 1.72, P = 0.04), and group 1 (HR 2.03, P = 0.02) were independently associated with the composite outcome.Checking for the resting OV prior to incremental exercise during CPX testing may be helpful in risk-stratification among subjects with advanced heart failure.

Background Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca2+ handling has a considerable effect on AF recurrence. The histidine-rich calcium-binding protein (HRC) genetic single nucleotide polymorphism (SNP), rs3745297 (T>G, Ser96Ala), is known to cause a sarcoplasmic reticulum Ca2+ leak. We investigated the association between HRC Ser96Ala and AF recurrence after RFCA in paroxysmal AF (PAF) patients. Methods and results We enrolled PAF patients who underwent RFCA (N = 334 for screening and N = 245 for replication) and were genotyped for HRC SNP (rs3745297). The patient age was younger and rate of diabetes and hypertension lower in the PAF patients with Ser96Ala than in those without (TT/TG/GG, 179/120/35; 64±10/60±12/59±13 y, P = 0.001; 18.5/ 9.2/8.6%, P = 0.04 and 66.1/50.0/37.1%, P = 0.001, respectively). During a mean 19 month follow-up, 57 (17.1%) patients suffered from AF recurrences. The rate of an Ser96Ala was significantly higher in patients with AF recurrence than in those without in the screening set (allele frequency model: odds ratio [OR], 1.80; P = 0.006). We also confirmed this significant association in the replication set (OR 1.74; P = 0.03) and combination (P = 0.0008). A multivariate analysis revealed that the AF duration, sinus node dysfunction, and HRC Ser96Ala were independent predictors of an AF recurrence (hazard ratio [HR], 1.04, P = 0.037; HR 2.42, P = 0.018; and HR 2.66, P = 0.007, respectively). Conclusion HRC SNP Ser96Ala is important as a new genetic marker of AF recurrence after RFCA.

The BLOCK HF trial showed that heart failure patients with atrioventricular block (AVB) and left ventricular systolic dysfunction (LVSD) are considered good candidates for cardiac resynchronization therapy (CRT), even though they have a narrow QRS duration. We aimed to compare the clinical response to CRT between patients with AVB combined with LVSD and patients with pre-existing CRT indications.We compared the clinical data on CRT across the following 3 groups in 3 cardiovascular centers; heart failure patients with an LV ejection fraction (LVEF) of ≤35% who had a QRS duration of ≥120ms (standard indication, n=125), those needing an upgrade to CRT (upgrade, n=49), and patients with an LVEF of ≤50% who had advanced AVB (AVB with LVSD, n=27).The prevalence of left bundle branch block differed significantly across the groups (87.2%, 98.0% and 40.7%; P0.001). No inter-group difference was found in the percentage of patients in whom clinical composite score (CCS) assessed 6months after the CRT was improved (60.8%, 57.1% and 70.4%; P=0.67). Whereas, even among the patients with an improved CCS, a significantly smaller LV end-systolic volume reduction after the CRT was seen in the ABV with LVSD group (-35.3±34.7, -21.4±28.5 and -5.2±23.9%; P=0.001). The incidence of cardiovascular death or hospitalization from heart failure within 5years occurred with a similar frequency (44%, 55.1% and 44.4%; P=0.9).As compared to patients with preexisting CRT indications, CRT may be similarly effective for patients with AVB and LVSD, however, LV reverse remodeling may be uncommon among them.

Background Risk stratification for ventricular fibrillation (VF) in patients with Brugada syndrome (BrS) remains controversial. Objective The purpose of this study was to construct a novel prediction model for VF risk in BrS patients using noninvasive parameters. Methods A total of 143 Japanese BrS patients with VF (n = 35) and without VF (n = 108) were retrospectively enrolled. We built a logistic regression model predicting VF occurrence and evaluated it by cross-validation. Results Frequencies of history of syncope and spontaneous type 1 ECG, r–J interval in V 1 , QRS duration in V 6 , and LAS 40 , Tpeak–Tend dispersion, and max T-wave alternans were significantly associated with VF occurrence in univariate analyses. The history of syncope, r–J interval in V 1 , QRS duration in V 6 , and Tpeak–Tend dispersion were identified as independent predictors by multivariate logistic regression analysis. The predictive model was constructed using all these parameters with good discrimination of VF occurrence (area under the curve 0.869 with 97.1% sensitivity and 65.7% specificity). The area under the curve based on leave-one-out cross-validation was 0.845, with 97.1% sensitivity and 63.0% specificity suggesting good performance of the model. Retrospective survival analysis revealed that the cumulative VF event rate was significantly higher in patients at high risk than in those with low risk using the log rank test ( P = 2.97 × 10 –8 ). Notably, no BrS patient below the cutoff value developed a subsequent VF event. Conclusion This novel prediction method may effectively assesses VF risk in BrS patients, especially when determining implantable cardioverter-defibrillator placement for asymptomatic BrS patients.

AV Nodal Remodeling Induced by AFBackground An animal experiment showed that long-term atrial pacing or persistent atrial fibrillation (AF) caused electrical remodeling of the atrioventricular (AV) node. We aimed to test the hypothesis that persistent AF decreases the AV conductivity in human hearts. Methods and Results We retrospectively compared the cardiac electrophysiological properties between patients with paroxysmal AF who underwent catheter ablation (PXAF, N = 254) and those with persistent or longstanding persistent AF (PSAF, N = 213). The PSAF patients were more likely than PXAF patients to have longer atrial-His (AH) (96.3 ± 25.7 vs. 91.3 ± 20.4 milliseconds; P = 0.02) and His-ventricle (HV) (43.1 ± 9.4 vs. 41.2 ± 8.6 milliseconds; P = 0.02) intervals. The AV nodal effective refractory period (ERP) (299.1 ± 74.6 vs. 276.2 ± 58.9 milliseconds; P < 0.001) and Wenckebach cycle length (420.9 ± 80.3 vs. 386 ± 58.6 milliseconds; P < 0.001) were also more prolonged in the PSAF patients. We found a dual AV nodal physiology with a similar frequency in both groups. The AH interval, fast pathway ERP, and Wenckebach cycle length in the PSAF patients were more likely than in the PXAF patients to be prolonged among the patients without dual pathways, while those intergroup differences were never seen among the patients with dual pathways. In subgroup analyses including only PSAF patients, there was no difference in the AV conductivity between the patients with persistent AF and those with longstanding persistent AF. Conclusions Persistent AF may cause a mild decrease in the AV nodal function in human hearts. Electrical remodeling may be uncommon if dual AV nodal pathways are present, and its extent may not depend on the duration of persistent AF.

Background The impact of subclinical hypothyroidism on the cardiovascular risk is still debated. We aimed to measure the relationship between subclinical hypothyroidism and the left atrial (LA) pressure. Methods The LA pressures and thyroid function were measured in consecutive patients undergoing atrial fibrillation (AF) ablation, who did not have any known heart failure, structural heart disease, or overt thyroid disease. Results Subclinical hypothyroidism (4.5≤ thyroid-stimulating hormone P = 0.04). The mean LA pressure (10.9 ± 4.7 vs 9.1 ± 4.3 mmHg; P = 0.002) and LA V-wave pressure (17.4 ± 6.5 vs 14.3 ± 5.9 mmHg; P < 0.001) were, respectively, higher in the patients with subclinical hypothyroidism than in the euthyroid patients. After an adjustment for potential confounders, the LA pressures remained significantly higher in the subclinical hypothyroidism patients. A multiple logistic regression model showed that subclinical hypothyroidism was independently associated with a mean LA pressure of >18 mmHg (odds ratio 3.94, 95% CI 1.28 11.2; P = 0.02). Conclusions Subclinical hypothyroidism may increase the LA pressure in AF patients.

Aims A worldwide survey reported that the success rate of atrial fibrillation (AF) ablation was higher in high-volume centers compared with low-volume centers. We tested whether the procedure volume of each operator was associated with the outcome of AF ablation in high-volume centres. Methods and results We studied 471 patients with paroxysmal AF who underwent pulmonary vein (PV) isolation for the first time in three cardiovascular centers where the annual AF ablation volume was >100 procedures. We classified a total of 10 primary operators according to their operation volume on the basis of ACC/AHA/ACP CLINICAL COMPETENCE STATEMENT; high-volume operator (≥50 cases/year, N = 3) or low-volume operator (

Periprocedural bleeding and thromboembolic events are worrisome complications of catheter ablation for atrial fibrillation (AF). Periprocedural anticoagulation management could decrease the risk of these complications. However, evaluation of the complications from pulmonary vein isolation using cryoballoon related to different anticoagulation strategies is limited. Therefore, we aimed to compare prothrombotic responses as assessed on the basis of d-dimer levels between the uninterrupted and interrupted apixaban therapies during cryoballoon ablation. Ninety-seven consecutive patients with paroxysmal AF scheduled to undergo cryoballoon ablation were randomly assigned in a 1:2 ratio to uninterrupted apixaban therapy (Group 1, n = 32) or interrupted apixaban therapy (Group 2, n = 65). d-Dimer levels were measured immediately before the ablation, at the end of the ablation, and 24 and 48 h after the procedure. No statistical difference was observed in the baseline characteristics between the two groups. The rates of hemorrhagic complications were similar in both groups (major bleeding: 3.1 vs. 1.5%; p = 0.61, and minor bleeding: 3.1 vs. 4.6%; p = 0.73, respectively). No thromboembolic events occurred in either group. However, d-dimer levels 48 h after the ablation increased more markedly following the procedure in Group 2 than in Group 1 (from 0.58 ± 0.16 to 1.01 ± 0.42 μg/mL vs. 0.58 ± 0.20 to 0.82 ± 0.25 μg/mL; p = 0.01). In conclusion, uninterrupted apixaban therapy during the periprocedural period of cryoballoon ablation for AF did not increase the risk of bleeding in this study and might reduce the periprocedural risk of subclinical hypercoagulable state.

Background: Tachycardia-induced cardiomyopathy (TIC) is a reversible cardiomyopathy induced by tachyarrhythmia, and the genetic background of the TIC is not well understood. The hyperpolarization-a...

Urinary liver-type fatty acid-binding protein (L-FABP) is a potential biomarker for acute kidney injury, and it in turn increases cardiovascular mortality. We tested whether the urinary L-FABP level predicted short- and mid-term outcomes in patients with acute heart failure.We enrolled consecutive patients with acute heart failure, and measured their urinary L-FABP levels before acute treatment. Worsening renal function (WRF), defined as both an absolute increase in the serum creatinine level of ≥0.3mg/dL and a ≥25% relative increase in its level from baseline, occurred in 37 (26.8%) of 138 patients. Patients with a urinary L-FABP level above the upper normal limit (8.4 µg/g creatinine) (n = 49; 35.5%) were more likely than those with a urinary L-FABP level within normal limits (n = 89; 64.5%) to develop WRF (n = 26 [53.1%] vs n = 11 [12.4%]; P.001). A urinary L-FABP level above the upper limit was independently associated with WRF (hazard ratio 1.8; P = .01). During 1 year of follow-up, 12 patients (8.7%) died, and urinary L-FABP level had no association with all-cause mortality. There was, however, a tendency toward a higher readmission rate in patients with a urinary L-FABP level above the upper normal limit who survived the index hospitalization (n = 46) than in those without an abnormal L-FABP level (n = 88; n = 13 [28.3%] vs n = 13 [14.8%]; log-rank P = .06).Increased urinary L-FABP level before treatment may predict WRF in patients with acute heart failure. Further investigation is warranted for its predictive ability of adverse outcomes.

Introduction The single nucleotide polymorphism (SNP) rs2106261 in the transcription factor gene ZFHX3 (16q22), a major regulator of inflammation, has been reported linking to atrial fibrillation (AF) by genome-wide association studies. Inflammation is known to be a strong predictor of atrial fibrillation recurrence after ablation, so we examined the association of the ZFHX3 SNP rs2106261 to inflammation marker expression and recurrence after AF ablation. Methods We genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls. We also analyzed associations between ZFHX3 SNP rs2106261 genotype and recurrence rate after pulmonary vein isolation and the inflammation markers. Results The minor (T) allele frequency of the ZFHX3 SNP rs2106261 was significantly higher in AF patients than non-AF controls (odds ratio 1.52, p = 2.2×10−5). Multivariable analysis revealed that the minor allele (T) decreased AF recurrence rate after pulmonary vein isolation (hazard ratio 0.53, p = 0.04). Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04). Conclusions The ZFHX3 SNP rs2106261 minor allele is associated with lower AF recurrence rate after pulmonary vein isolation. Low baseline inflammation conferred by this allele may reduce AF recurrence risk.

Background A common SCN5A polymorphism H558R (c.1673 A > G, rs1805124) improves sodium channel activity in mutated channels and known to be a genetic modifier of Brugada syndrome patients (BrS). We investigated clinical manifestations and underlying mechanisms of H558R in BrS. Methods and results We genotyped H558R in 100 BrS (mean age 45 ± 14 years; 91 men) and 1875 controls (mean age 54 ± 18 years; 1546 men). We compared clinical parameters in BrS with and without H558R (H558R+ vs. H558R- group, N = 9 vs. 91). We also obtained right atrial sections from 30 patients during aortic aneurysm operations and compared SCN5A expression and methylation with or without H558R. H558R was less frequent in BrS than controls (9.0% vs. 19.2%, P = 0.028). The VF occurrence ratio was significantly lower (0% vs. 29.7%, P = 0.03) and spontaneous type 1 ECG was less observed in H558R+ than H558R- group (33.3% vs. 74.7%, P = 0.01). The SCN5A expression level was significantly higher and the methylation rate was significantly lower in sections with H558R (N = 10) than those without (0.98 ± 0.14 vs. 0.83 ± 0.19, P = 0.04; 0.7 ± 0.2% vs. 1.6 ± 0.1%, P = 0.004, respectively). In BrS with heterozygous H558R, the A allele mRNA expression was 1.38 fold higher than G allele expression. Conclusion The SCN5A polymorphism H558R may be a modifier that protects against VF occurrence in BrS. The H558R decreased the SCN5A promoter methylation and increased the expression level in cardiac tissue. An allelic expression imbalance in BrS with a heterozygous H558R may also contribute to the protective effects in heterozygous mutations. Electronic supplementary material The online version of this article (doi: 10.1186/s12929-017-0397-x) contains supplementary material, which is available to authorized users.

Aims Abnormal sympathetic innervation triggers ventricular fibrillation (VF). We examined the circadian variation of autonomic nervous system and its relevance to risk stratification of VF in patients with Brugada syndrome (Brs). Methods We enrolled 12 male Brs patients with documented VF (Brs-S; mean age, 42 ± 4 years), 17 without documented VF (Brs-N; mean age 48 ± 4 years), and 16 age- and gender-matched controls. The clinical data, 12-lead electrocardiography (ECG), signal-averaged ECG, electrophysiological study (EPS), and heart rate variability from 24 h Holter ECG were compared between the groups. Results The low frequency components (LF) in Brs-S and Brs-N and high frequency components (HF) in Brs-S patients were significantly lower than in the controls (409.8 ± 128.6 ms 2 , 329.5 ± 108 ms 2 vs. 945.3 ± 111.3 ms 2 ; 135.1 ± 73.8 ms 2 vs. 391.8 ± 63.9 ms 2 , respectively). The circadian variation of the LF and LF/HF decreased in the Brs patients, the standard deviation (SD) of LF/HF ( 2 ) had sufficiently high sensitivity (96.6%) and specificity (92.9%) for the diagnosis of Brs. Most of the Brs-S patients (83.3%) were located under the line formed by the SD/mean of HF = SD/mean of LF in the scatter plots. Conclusion Lack of the circadian variation of autonomic function occurs in Brs, and this may contribute to the pathogenesis of VF.

Time-Domain T-Wave Alternans and Brugada Syndrome Aims T-wave alternans (TWA) is an indicator of vulnerability to ventricular arrhythmias and is useful for predicting sudden cardiac death (SCD) in patients with various structural heart diseases. We evaluated whether high levels of time-domain TWA on ambulatory ECG (AECG) are associated with a history of ventricular fibrillation (VF) in Brugada syndrome (BrS) patients. Methods and Results We examined the associations among VF history, family history of SCD, spontaneous type 1 electrocardiogram (ECG), late potentials, VF induction by programmed electrical stimulation, and TWA in 45 BrS patients (44 males; mean age, 45 ± 15 years). TWA analyzed from 24-h AECG recordings using the modified moving average method was positive in 13 of 43 patients (30%). Patients with a history of VF had a significantly higher incidence of a positive TWA test (82% vs. 13%; P < 0.001) and spontaneous type 1 ECG (92% vs. 38%; P = 0.007) than those without VF history. Multivariate analysis indicated that positive TWA (OR 7.217; 95% CI 2.503–35.504; P = 0.002) and spontaneous type 1 ECG (OR 5.530; 95% CI 1.651–34.337; P = 0.020) were closely associated with VF history. Spontaneous type 1 ECG had high sensitivity (92%) but low specificity (63%). Positive TWA was a reliable marker with high sensitivity and specificity (82% and 88%, respectively). Conclusion Elevated time-domain TWA on AECG confirms arrhythmia risk in symptomatic BrS patients without the need for provocative stimuli.

Incomplete Cure of TIC with Rate ControlBackground It is uncertain whether rate or rhythm control is more favorable for patients experiencing tachycardia-induced cardiomyopathy (TIC) secondary to rapid atrial fibrillation (AF). Methods and Results We compared the electrophysiological and hemodynamic properties and outcome after AF ablation in 20 patients with a history of decompensated TIC who maintained sinus rhythm or had paroxysmal AF (group 1), 32 with a history of decompensated TIC who had persistent or longstanding persistent AF (group 2), 377 without TIC who had paroxysmal AF (group 3), and 225 without TIC who had persistent or longstanding persistent AF (group 4). The corrected sinus node recovery time was more prolonged in group 2 than in groups 1, 3, or 4 (1,066 ± 946 vs. 416 ± 188, 450 ± 322 and 590 ± 329 milliseconds; P < 0.001, respectively). The mean left atrial pressure in group 2 was greater than that in groups 1, 3, or 4 (13.9 ± 6.5 vs. 7.5 ± 3.1, 8.2 ± 4.1 and 10.8 ± 4.2 mmHg; P < 0.001, respectively). The left ventricular ejection fraction assessed after the recovery from the decompensation was more decreased in group 2 than in group 1; however, it almost returned to normal if sinus rhythm was maintained after the AF ablation in group 2. The presence of a history of TIC did not predict an AF recurrence after the ablation. Conclusions Heart rate control during AF without sinus conversion may result in an incomplete cure of TIC, suggesting the advantages of rhythm control with ablation in patients with TIC.

Two new oral anticoagulants, rivaroxaban and dabigatran, with no need for anticoagulation monitoring, are available for patients with atrial fibrillation (AF). We aimed to compare their anticoagulant effects and safety when used during the AF ablation periprocedural period. Patients undergoing AF ablation were randomly assigned to receive rivaroxaban 15 mg once daily (N = 30) or dabigatran 110 mg twice daily (N = 30). Rivaroxaban was withheld on the morning of the day before the ablation, and dabigatran was discontinued from the evening of the day before the procedure. Both anticoagulants were then resumed after haemostasis of the access site. D-dimer levels were measured just before the ablation, at the end of the ablation, and at 24 h and 48 h after the procedure. The baseline D-dimer levels were identical in both groups. However, D-dimer levels increased more markedly following the ablation procedure in patients receiving rivaroxaban than in those receiving dabigatran (mean ± standard deviation from 0.62 ± 0.16 to 1.09 ± 0.38 μg/mL vs from 0.59 ± 0.08 to 0.75 ± 0.17 μg/mL; p

Background Inappropriate shocks resulting from atrial tachyarrhythmias are highly problematic for patients with an implantable cardioverter defibrillator (ICD). We aimed to determine the effectiveness of catheter ablation of atrial fibrillation (AF) in preventing inappropriate shocks due to rapid AF in patients diagnosed with Brugada syndrome (BS) who were implanted with an ICD. Methods We performed AF ablation in 5 BS patients with ICDs who experienced inappropriate shocks caused by rapid paroxysmal AF and in a BS patient scheduled to determine an indication of an ICD implantation who frequently experienced rapid AF. Results Although 2 patients underwent a 2nd ablation procedure because of AF recurrences, 5 of the 6 patients were finally free from AF after their last procedure during a median follow-up period of 43.2months. No further inappropriate shocks caused by rapid AF occurred after the 1st ablation session in any of the patients. A patient developed a ventricular fibrillation storm during his electrophysiological study following the ablation procedure, and then was implanted with an ICD. Conclusions AF ablation in BS patients may be reasonable to prevent inappropriate ICD shocks resulting from rapid AF. However, ventricular extrastimuli just after the ablation had better be avoided in them.

Variable Strategies for CTI Ablation Objectives This study aimed to investigate the anatomical characteristics complicating cavotricuspid isthmus (CTI) ablation and the effectiveness of various procedural strategies. Methods and Results This study included 446 consecutive patients (362 males; mean age 60.5 ± 10.4 years) in whom CTI ablation was performed. A total of 80 consecutive patients were evaluated in a preliminary study. The anatomy of the CTI was evaluated by multidetector row-computed tomography (MDCT) prior to the procedure. A multivariate logistic regression analysis revealed that the angle and mean wall thickness of the CTI, a concave CTI morphology, and a prominent Eustachian ridge, were associated with a difficult CTI ablation (P < 0.01). In the main study, 366 consecutive patients were divided into 2 groups: a modulation group (catheter inversion technique for a concave aspect, prominent Eustachian ridge, and steep angle of the CTI or increased output for a thicker CTI) and nonmodulation group (conventional strategy). The duration and total amount of radiofrequency energy delivered were significantly shorter and smaller in the modulation group than those in the nonmodulation group (162.2 ± 153.5 vs 222.7 ± 191.9 seconds, P < 0.01, and 16,962.4 ± 11,545.6 vs 24,908.5 ± 22,804.2 J, P < 0.01, respectively). The recurrence rate of type 1 atrial flutter after the CTI ablation in the nonmodulation group was significantly higher than that in the modulation group (6.3 vs 1.7%, P = 0.02). Conclusion Changing the procedural strategies by adaptating them to the anatomical characteristics improved the outcomes of the CTI ablation.

Background Sleep-disordered breathing (SDB) frequently is induced by sedation during ablation of atrial fibrillation (AF). We tested whether or not sedative-induced SDB is associated with clinical sleep apnea syndrome (SAS). Methods We examined SDB observed during intra-ablation sedation with a novel portable respiratory monitor (PM), SD-101, in 140 patients undergoing AF ablation without any known SAS. A sleep study was repeated the next night of the ablation with the simultaneous use of the SD-101 and type 3 PM, APNOMONITOR V. Results The respiratory disturbance index (RDI) during sedation (20.0±7.8events/h) was significantly correlated with the RDI measured by the SD-101 during the night (15.8±13.7events/h; r =0.50) and the RDI assessed by the APNOMONITOR V during the night (12.7±12.3events/h; r =0.55). An excellent agreement was found between the RDIs simultaneously measured with the 2 PMs (intraclass correlation coefficient, 0.84), especially for an RDI of ⩾30events/h ( κ statistic value, 0.82). The area under the receiver-operating characteristic curve for the RDI with the use of the SD-101 during sedation to identify the patients with an RDI of ⩾30events/h by both PMs during the night was 0.92. A left atrial diameter of >40mm (odds ratio [OR], 4.10) and an RDI during sedation of >20events/h (OR, 17.75) were independently associated with having an RDI of ⩾30events/h with both PMs during the night. Conclusions Frequent episodes of sedative-induced SDB may have a diagnostic value for SAS in patients with AF.

It has been reported that dexmedetomidine (dex) has an impact on the cardiac conduction system and even has potential antiarrhythmic actions. We examined the influence of dex on the cardiac electrophysiological properties and atrial fibrillation (AF) inducibility. Adult paroxysmal AF patients were randomly assigned to receive (N = 107) or not receive (N = 108) dex during cardiac electrophysiological studies. The corrected sinus node recovery time (558 ± 331 vs. 459 ± 260 milliseconds; P = 0.02), Wenckebach cycle length (P < 0.001), atrioventricular nodal effective refractory period (317 ± 76 vs. 252 ± 54 milliseconds; P < 0.001), and atrio-His interval (P < 0.001) were longer in patients with dex than in those without. We tested the induction of repetitive atrial firing (RFA) defined as the occurrence of ≥2 successive atrial activities induced by single premature atrial stimuli to determine the AF inducibility. RFA was seen with a similar proportion (41.1% vs. 44.4%), yet it was evoked at a longer stimulus coupling interval in the dex patients, which was potentially attributed to the longer atrial effective refractory period (237 ± 36 vs. 213 ± 27 milliseconds; P < 0.001) and more prolonged atrial conduction delay seen in the dex group. In conclusion, dex may depress the sinus and atrioventricular nodal function, however, it may not reduce the AF inducibility.

Aims Sarcoidosis with cardiac involvement is a rare pathological condition, and therefore cardiac resynchronization therapy (CRT) for patients with cardiac sarcoidosis is even further rare. We aimed to clarify the clinical features of patients with cardiac sarcoidosis who received CRT. Methods and results We retrospectively reviewed the clinical data on CRT at three cardiovascular centres to detect cardiac sarcoidosis patients. We identified 18 (8.9%) patients with cardiac sarcoidosis who met the inclusion criteria out of 202 with systolic heart failure who received CRT based on the guidelines. The majority of the patients were female [15 (83.3%)] and underwent an upgrade from a pacemaker or implantable cardioverter defibrillator [13 (72.2%)]. We found 1 (5.6%) cardiovascular death during the follow-up period (mean ± SD, 4.7 ± 3.0 years). Seven (38.9%) patients had a composite outcome of cardiovascular death or hospitalization from worsening heart failure within 5 years after the CRT. Twelve (66.7%) patients had a history of sustained ventricular arrhythmias or those occurring after the CRT. Among the overall patients, no significant improvement was found in either the end-systolic volume or left ventricular ejection fraction (LVEF) 6 months after the CRT. A worsening LVEF was, however, more likely to be seen in 5 (27.8%) patients with ventricular arrhythmias after the CRT than in those without (P = 0.04). An improved clinical composite score was seen in 10 (55.6%) patients. Conclusions Cardiac sarcoidosis patients receiving CRT may have poor LV reverse remodelling and a high incidence of ventricular arrhythmias.

Cancer therapeutics-related cardiac dysfunction induced by anthracycline is highly problematic, and its early recognition is of importance. Atrial fibrillation (AF) is sometimes seen after anthracycline chemotherapy. We aimed to test whether new-onset AF predicts anthracycline-induced heart failure. We prospectively studied 249 lymphoma patients who received anthracyclines. The patients were followed up with a frequent electrocardiographic examination. Fifteen patients (6%) newly developed AF after the chemotherapy, and during a mean follow-up of 34 months, they had a higher incidence of acute heart failure (40% vs 3.8%; p0.001) and greater all-cause mortality (60% vs 14.1%; p0.001) than those without AF. The onset of AF preceded the development of heart failure by a mean of 2.4 months. New-onset AF was independently associated with both acute heart failure (hazard ratio 12.78; p0.001) and all-cause mortality (hazard ratio 4.77; p0.001). The cumulative anthracycline dose did not differ between the patients with and without heart failure, yet it was another independent predictor of the mortality. In conclusion, new-onset AF may predict unfavorable outcomes after anthracycline chemotherapy in patients with malignant lymphoma.

Background— Risk stratification of Brugada syndrome (BrS) remains controversial and the majority of patients with BrS have no genetic explanation. We investigated relationships between genotypes of 3 single-nucleotide polymorphisms reported in a recent genome-wide association study and BrS phenotypes. Methods and Results— SCN10A (rs10428132), SCN5A (rs11708996), and downstream from HEY2 (rs9388451) single-nucleotide polymorphisms were genotyped and compared between 95 Japanese patients with BrS and 1978 controls. Relationships between the single-nucleotide polymorphisms and clinical characteristics, 12-lead ECG findings, signal-averaged ECG findings, and electrophysiological parameters were also examined in patients with BrS. Both rs10428132 and rs9388451 were significantly associated with BrS ( P =2.7×10 −14 ; odds ratio, 3.0; P =9.2×10 −4 ; odds ratio, 1.7, respectively). Interestingly, the HEY2 risk allele C was less frequent in BrS patients with ventricular fibrillation than in those without (59% versus 74%; P =4.1×10 −2 ; odds ratio, 0.5). A significant linear correlation was found between HEY2 genotypes and QTc interval (CC: 422±27 ms; CT: 408±21 ms; and TT: 381±27 ms; P = 4.0×10 −4 ). The HEY2 mRNA expression level in the right ventricular specimens from patients with BrS (n=20) was significantly lower in patients with CC genotype than the other genotypes ( P =0.04). Additionally, during 63±28 months follow-up periods after implantable cardioverter defibrillator implantation (n=90), Kaplan–Meier event-free survival curves revealed that the cumulative rate of ventricular fibrillation events was significantly lower in cases with HEY2 CC genotype ( P =0.04). Conclusions— Our findings suggest that HEY2 CC genotype may be a favorable prognostic marker for BrS, protectively acting to prevent ventricular fibrillation presumably by regulating the repolarization current.

Background We aimed to evaluate the feasibility of an oral direct thrombin inhibitor, dabigatran, as a periprocedural anticoagulant for use with ablation of atrial fibrillation (AF). Methods Consecutive patients scheduled to undergo an AF ablation were randomly assigned to receive dabigatran (n = 45) or warfarin (n = 45) to compare their clinical feasibility. Both of those oral anticoagulants were discontinued the day before the ablation and were resumed after confirming hemostasis of the venipuncture site. A bridging therapy with heparin was not used in either of the patient groups. Results Dabigatran was switched to warfarin before the ablation because of dyspepsia in three patients. An occurrence of rebleeding from the venipuncture site was less common in dabigatran-allocated patients than in warfarin-allocated patients (20% vs 44%; P = 0.013). The reduction in the D-dimer level after the initiation of oral anticoagulants was greater in the dabigatran-allocated patients than in the warfarin-allocated patients. The time from the initiation of the anticoagulants to the ablation was significantly shorter in the dabigatran-allocated patients than in the warfarin-allocated patients (43 ± 7 vs 63 ± 13 days; P < 0.0001). There was only one fatal periprocedural complication in a patient receiving warfarin, who had a mesenteric arterial thrombosis after the ablation. Conclusions An anticoagulation strategy with dabigatran may surpass that with warfarin in reducing both the periprocedural risk of minor bleeding and a hypercoagulable state, and the time to ablation in patients undergoing ablation of AF.

Background The indications for catheter ablation have been expanded to include persistent atrial fibrillation (AF) to enable a high degree of sinus rhythm maintenance. We occasionally encounter patients undergoing pacemaker implantation in whom sick sinus syndrome became clinically evident after ablation. This study investigated whether underlying sinus node dysfunction (SND) during persistent AF can be predicted before deciding the indications for ablation. Methods and results In total, 87 consecutive patients with persistent AF who underwent catheter ablation between January 2010 and July 2011 were enrolled in the study. Nocturnal polysomnography as well as transthoracic and transesophageal echocardiography were performed in all patients before ablation. We used the double Lasso catheter and electroanatomical mapping-guided extensive encircling pulmonary vein isolation (EEPVI) method. We performed electrophysiological studies after EEPVI, and SND was defined as a corrected SN recovery time of ≥550 ms. SND was detected in 42 (48%) 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. 17.5 ± 11, p = 0.002). Multivariate analysis revealed that moderate to severe sleep-disordered breathing (defined as AHI ≥ 15) was an independent predictor of SND after catheter ablation for persistent AF. Conclusion The results suggest that underlying SND in patients with persistent AF can be predicted by evaluating sleep-disordered breathing before catheter ablation.

High-frequency stimulation (HFS) of the atria induces atrial fibrillation (AF) when applied during sinus rhythm and elicits a parasympathetic response when delivered at sites where ganglionated plexi (GPs) are located. However, little is known about its impact after an electrophysiological study.To evaluate the impact of HFS on the short-term and long-term outcomes after the ablation of persistent AF.Thirty consecutive patients with persistent or long-standing persistent AF were randomly assigned to either receive HFS of the left atrium (n = 15) or not (n = 15) during their electrophysiological studies. Patients receiving HFS were examined to determine whether or not a vagal response was elicited by the HFS at sites where GPs were located before and after conventional pulmonary vein isolation without any ablation targeting the GPs. Patients not receiving the HFS underwent the ablation procedure alone. The rate of recurrence of AF within 3 months of the procedure (early recurrence [ER]) and the frequency of that occurring after that period (late recurrence) were compared between the patient groups.The incidence of ER occurred more frequently in patients with HFS than in those without (80% vs 40%; P = .015), whereas the occurrence of late recurrence was similar between the 2 groups (27% vs 33%; P = .73). In the HFS group, the number of GPs decreased from 3.4 ± 1.1 to 1.5 ± 0.8 after the pulmonary vein isolation (P.0001), and the decrease was smaller in the patients experiencing ER than in those without.HFS increases the incidence of ER in patients with persistent AF despite a partial GP modification resulting from the pulmonary vein isolation.

AF Ablation in HD Patients. Introduction: It is not common for patients on chronic hemodialysis (HD) to undergo catheter ablation of atrial fibrillation (AF). We aimed to show the outcomes of AF ablation in the HD patients. Methods and Results: Thirty HD patients who underwent pulmonary vein (PV) isolation for drug refractory paroxysmal AF were retrospectively studied, and their AF recurrence free rate and frequency of periprocedural complications were compared to 60 age- and gender-matched control patients not requiring HD. A nonirrigated ablation catheter was used in both patient groups. During a mean follow-up period of 821 ± 218 days, 16 (54%) of the HD patients remained free from AF recurrence without any antiarrhythmic agents versus 47 (78%) of the control patients with an initial ablation (P = 0.013). A second ablation procedure was performed in 12 patients with an AF recurrence, and consequently 20 (67%) of the HD patients were in sinus rhythm compared to 53 (88%) of the controls during a follow-up duration of 747 ± 221 after the last ablation (P = 0.012). Bleeding from the venipuncture site requiring a prolonged hospital stay was identified in 2 HD patients and 1 control subject, while no life-threatening complications were observed in either patient group. Conclusion: Although the success rate of the PV isolation in HD patients was far from satisfactory, it may be considered as one of the therapeutic options for them. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1289-1294, December 2012)

Atrioventricular (AV) conduction disturbances have often been considered as an etiology of prolonged pauses during atrial fibrillation (AF). We aimed to test whether there was a significant difference in the AV conduction properties between patients with and without clinically significant pauses who underwent ablation of longstanding persistent AF. Ninety-nine patients undergoing ablation of longstanding persistent AF were divided into three groups according to the extent of pauses documented on the ambulatory electrocardiogram during AF; patients without pauses (n = 25), with pauses of

Aims We aimed to determine how many electrical cardioversions (ECs) should be applied to treat repetitive persistent recurrences of atrial fibrillation (AF) following ablation of persistent AF within the early post-procedural period. Methods and results A total of 40 patients with >1 episode of recurrent AF in the form of persistent atrial arrhythmias within 3 months following the ablation were recruited from 108 patients who underwent ablation for persistent or long-standing persistent AF. Electrical cardioversions were applied up to six times, if necessary, to restore sinus rhythm at clinical visits at 2-week intervals until 3 months after the ablation. Fourteen (35%) ablation failures defined as recurrences of AF identified from the 3rd month after the ablation procedure were finally diagnosed during the follow-up period (14 ± 4 month). The patients with an ablation failure more frequently required ECs than those without (3.7 ± 0.3 vs. 1.2 ± 0.2 times; P < 0.0001). A receiver-operating characteristic curve identified a number of ECs of ≥3 as the optimal cut-off value for predicting an ablation failure (area under the curve 0.91; sensitivity, 86%, and specificity, 96%; P = 0.0007). In the multivariate logistic regression analysis, a number of ECs of ≥3 was the only independent predictor of an ablation failure (odds ratio, 11.32; 95% confidence interval, 3.83–58.22; P = 0.0019). Conclusion It was difficult to maintain sinus rhythm in patients with persistent AF who required several ECs for recurrences of AF within the early post-ablation period.

Summary Purpose We evaluated whether time-dependent procedural improvement was independently associated with reduction in atrial fibrillation (AF) recurrences or periprocedural complications in patients who underwent catheter ablation for AF at a single medium-volume center. Methods A total of 208 consecutive patients who underwent AF ablation from June 2006 to June 2009 were enrolled. All procedures were performed by an experienced operator, and the ablation protocol, devices, and equipment remained unchanged throughout the study period. The study period was divided into quarters (1–4 Q) to include the same number of patients within each quarter. The incidence of AF recurrences or periprocedural complications requiring a prolonged hospital stay or surgical intervention was retrospectively compared across the quarters. Results During follow-up (15 ± 3 months), we observed 26 (13%) AF recurrences (27% in 1Q, 15% in 2Q, 6% in 3Q, 2% in 4Q; 1Q vs. 3Q, p = 0.0035; 1Q vs. 4Q, p = 0.0003; 2Q vs. 4Q, p = 0.013) and 15 (7%) periprocedural complications (12% in 1Q, 8% in 2Q, 6% in 3Q, 4% in 4Q), both of which declined progressively over time. Multiple logistic regression analysis revealed that 1Q, but not any other patient background parameters, was an independent predictor of the incidence of AF recurrence or periprocedural complications (odds ratio, 2.45; 95% confidence interval, 1.19–5.20; p = 0.015). Conclusions The time period when the procedure was performed significantly influenced the AF ablation outcome, indicating that operators in medium-volume centers should be committed to providing gratifying outcomes particularly early in the institutional experience with AF ablation.

Left atrial (LA) remodeling progresses to electrical remodeling, contractile remodeling, and subsequently structural remodeling. Little is known about the relationship between LA electrical and anatomical remodeling and LA mechanical function.We aimed to clarify the relationship between LA mechanical function using 3-dimensional speckle-tracking echocardiography (3D-STE) and LA electrical remodeling using an electroanatomic mapping system (CARTO 3) and to estimate atrial fibrillation (AF) substrate in patients with paroxysmal AF (PAF).A total of 52 patients with PAF (41 (79%) men; mean age 61 ± 11 years) undergoing their initial pulmonary vein isolation (PVI) were examined. The standard deviation of the time to peak strain in each LA segment (%SD-TPS) was analyzed as an index of LA dyssynchrony using 3D-STE before PVI. Contact LA bipolar voltage and activation maps were constructed during sinus rhythm before PVI using CARTO 3. The LA total activation time was measured and low-voltage zones (LVZs) were determined with a local bipolar electrogram amplitude of0.5 mV. The patients were divided into those with an LVZ (LVZ group; n = 23) and those without an LVZ (non-LVZ group; n = 29).The %SD-TPS was significantly higher (14.1 ± 5.7 vs 8.0 ± 5.1; P=.0002) in the LVZ group than in the non-LVZ group and was an independent determinant of the LVZ (odds ratio 1.21; 95% confidence interval 1.04-1.49; P=.01). In addition, the LA total activation time was weakly correlated with the %SD-TPS.LA dyssynchrony and conduction delay exist in patients with PAF. The 3D-STE enabled noninvasive estimation of LA electrical remodeling and AF substrate.

Although it is relatively rare, there are some patients with persistent or longstanding (LS) persistent atrial fibrillation (AF) who develop recurrences of AF with a paroxysmal form after pulmonary vein (PV) isolation [1]. Since there is no consensus on how to treat those patients, we tested what the results would be if they underwent a repeat ablation procedure. Consecutive patients were eligible for inclusion if they had any symptoms resulting from recurrent paroxysmal or persistent AF after PV isolation for the initial treatment of persistent or LS persistent AF, and then underwent a second ablation procedure. The types of AF were defined according to the current guidelines [2]. Written informed consent was obtained from all patients, and the study protocol was approved by the research committee of the institution. A double lasso guided extensive PV isolation with a cavotricuspid isthmus (CTI) ablation was performed in each patient as an initial ablation procedure. The details of the procedurewere described in our previous work [3]. In the second procedure, if any electrical reconnection was seen in the PVs or CTI, re-ablation was carried out in the samemanner as in the initial session. In principle, a roof line and anterior line [2] were additionally created if the patients had one or no reconnected PV. Finally, the superior vena cava was isolated circumferentially in all patients. The antiarrhythmic drugs withdrawn before the ablation were resumed the evening of the procedure in all patients. We scheduled to follow them up 3, 9, 12, and finally 24 months after the procedure to screen for any AF recurrences defined based on the current guidelines [2]. The end point was an AF recurrence occurring after the 2nd session in patients with a paroxysmal form of AF recurrence and those with a persistent form of AF recurrence after the 1st session.

Anticoagulation with novel oral anticoagulants (NOACs) for patients undergoing catheter ablation of atrial fibrillation (AF) has rapidly spread all over the world. Nevertheless, there is a lack of information on how to use the NOACs during the periprocedural period. In this review, we introduced the current trend in the way to use the NOACs during the periprocedural period of the AF ablation, and discussed its problems and future challenges.

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.

article i nfo Background:Restless patientisrecalcitrant during ablation of atrial fibrillation (AF). Weaimed toassess the asso- ciation between patient movements during AF ablation and its outcome. Methods: We examined the body movement during AF ablation in 78 patients with the use of a novel portable respiratory monitor, the SD-101, which also has the ability to quantify the frequency of body movements. Results: The body movement index, defined as the number of the units of time with body movement events di- videdby therecording time(11.4 ± 6.5 events/h), wassignificantlycorrelatedwith the ablation time defined as the time from the first point of the ablation to the end of the procedure (1.2 ± 0.3 h) (r = 0.35; p = 0.0014) and a total radiofrequency energy applied (56.6 ± 17.7 kW) (r = 0.36; p = 0.0015). A multiple linear regres- sion analysis showed that non-paroxysmal AF (β = 0.25; p = 0.036) and the body movement index (β = 0.36; p = 0.0019) were independent determinants of the ablation time. The body movement index was similar in patients with and without recurrence of AF. Conclusions: Keeping patients motionless may be important to reduce the procedural duration of AF ablation. © 2013 Elsevier Ireland. Ltd All rights reserved.

We aimed to examine what becomes of the coagulable state when warfarin is interrupted in patients undergoing ablation of atrial fibrillation (AF). We studied 62 patients with a CHADS2 score of 0 or 1 who underwent ablation for paroxysmal AF. Warfarin was discontinued the day before the ablation without heparin-bridging, and intravenous heparin was administered during the procedure in a conventional manner, and warfarin was then resumed after achieving hemostasis of the access site. The international normalized ratio (INR) values or D-dimer levels were measured at five different time points during the periprocedural period, and the periprocedural hemorrhagic and thromboembolic complications were assessed. The INR value constantly decreased after withdrawal of warfarin, and did not recover to the level before its discontinuation at the time of hospital discharge despite a short interruption of warfarin (mean ± SD, 1.75 ± 0.52 to 1.41 ± 0.27, p < 0.0001). However, the D-dimer level continued to increase over a period of 48 h after the ablation in spite of the administration of a sufficient amount of heparin during the procedure and a quick resumption of warfarin (mean ± SD, 0.57 ± 0.19 to 0.85 ± 0.36 μg/mL, p < 0.0001). The INR value measured just before the ablation had a significant inverse correlation to the D-dimer levels assessed just before (r = −0.304), immediately after (r = −0.440), 24 h after (r = −0.442) and 48 h after the ablation (r = −0.463). In conclusion, the risk of hyper-coagulability may increase during the early postprocedural period of AF ablation in patients who were inappropriately anticoagulated with warfarin.

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.