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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.

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.

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: Distinguishing left-and right-sided atrial tachycardia (AT) is often challenging. The coronary sinus (CS) provides information only concerning the anterior left atrium (LA). Potentials recorded in the pulmonary artery (PA) have been substituted for those of the upper posterior LA because of their anatomical relationship. Methods and Results: Three patterns were designed, using potentials in the PA, right atrium (RA) and CS, to predict the side of AT. Two patterns were for left-sided AT and 1 pattern was for right-sided AT. Ten left-sided and 11 right-sided ATs were investigated regardless of mechanism. Electrode catheters were inserted in the RA, His bundle region, and CS, and an ablation catheter was inserted into the left and/or right PA. The sequences from these catheters were analyzed before detailed electroanatomical mapping. Patterns were obtained for 20 of 21 ATs. The mechanism was focal in 16 ATs and macroreentry in 5. The method predicted left-sided AT with a sensitivity of 78%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 84%, and an accuracy of 90%. Conclusions: The use of potentials in PA combined with conventional RA and CS electrograms is useful for distinguishing left-sided AT from right-sided AT, regardless of mechanism. (Circ J 2013; 77: 345–351)

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.

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.

Background: Matrix metalloproteinases (MMPs) play an important role in degradation of the extracellular matrix of injured tissue. MMP-9 expression increases in fibrillating atrial tissue; however, the mechanism for this increase has not been clarified. Methods and Results: Changes in the expression of vascular endothelial growth factor (VEGF), VEGF receptors, and hypoxia-induced transcription factor-1α (HIF-1α) in fibrillating atrial tissue were investigated. Atrial tissue samples were obtained from 13 patients with atrial fibrillation (AF) and 25 patients without a history of AF (regular sinus rhythm, RSR) undergoing cardiac operations. Western blot, real-time polymerase chain reaction, and immunofluorescence analyses of the expression of VEGF, VEGF receptors, and HIF-1α were performed. The VEGF mRNA and protein levels increased significantly in the AF group compared with the RSR group (P

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.

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.

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.

Aim Risk stratification for Brugada syndrome remains controversial. We investigated the relationships between episodes of ventricular fibrillation (VF) and various clinical, electrocardiographic, electrophysiologic, and genetic parameters both retrospectively and prospectively. Methods and results Fifty-two patients with Brugada syndrome (49 men, average age 42 +/- 3 years) were studied. In the Brugada patients with a VF history, the frequency of a spontaneous Type 1 electrocardiogram (ECG) pattern in lead V2 was significantly higher and the STJ amplitude in the V1 and V2 leads was also higher than in those without a VF history. Multivariate analyses revealed that the spontaneous Type 1 ECG pattern in lead V2 (but not lead V1) was the only independent predictor of a VF history. During a mean follow-up period of 39 +/- 4 months, 38.8% of the patients with a VF history and 2.9% of those without experienced an appropriate implantable cardioverter-defibrillation owing to VF. A multivariate analysis using a Cox's proportional hazard model showed that a VF history and spontaneous Type 1 ECG pattern in lead V2 were independent predictors of subsequent VF events. Conclusion A spontaneous Type 1 Brugada ECG pattern in lead V2 (but not lead V1) was both a prospective and retrospective independent predictor of VF episodes in Brugada syndrome.

A 55 year-old man with huge coronary artery fistula to the right atrium is presented. The Qp/Qs ratio was 1.6. We failed to place simultaneously three interlocking detachable coils for closing the fistula, because the coils were washed out into the right atrium. We deployed the coronary stent at the distal portion of the coronary artery. This procedure enabled us to anchor 7 electrically or interlocking detachable coils and to interrupt the shunt flow. A Doppler flow wire was useful to reveal instantaneously the extent of flow reduction even when contrast angiography was not performed in each procedure.

Clinical manifestations of arrhythmogenic right ventricular cardiomyopathy (ARVC) are variable, and in some cases, ventricular fibrillation (VF) represents the first manifestation. In order to aid in the prevention of sudden cardiac death due to ARVC, we examined the clinical presentations of ARVC patients whose first sign was VF or another manifestation. Fifteen patients (male/female 7/8, mean age 47 years, ge of onset 41 years) diagnosed as having ARVC using the updated 2010 Task Force Criteria were included. The earliest symptoms were VF in 3 patients; ventricular tachycardia in 6 patients; heart failure in 3 patients; and ECG abnormality, family history, and premature ventricular contractions in 3 patients. We investigated clinical data based on 12-lead ECG, signal-averaged ECG (SAECG), Holter ECG, echocardiography, right ventricular biopsy, multidetector computed tomography (MDCT), magnetic resonance imaging, substrate mapping using an electroanatomical mapping system, and 123I-metaiodobenzylguanidine scintigraphy for all subjects. Repolarization abnormalities (inverted T waves in right precordial leads) and depolarization abnormalities (late potentials by SAECG) were observed in all patients. We made a remarkable MDCT observation in all patients whose earliest symptom was VF: trabeculae distal to the RV moderator band showed a netlike appearance. The other parameters were similar in patients with and without VF. This particular netlike appearance of RV may be a pathogenesis of VF in ARVC.

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.

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.