Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Different Determinants of the Recurrence of Atrial Fibrillation and Adverse Clinical Events in the Mid-Term Period After Atrial Fibrillation Ablation.

BACKGROUND: It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation.Methods and Results:We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences. CONCLUSIONS: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Clinical outcomes of ablation versus non-ablation therapy for atrial fibrillation in Japan: analysis of pooled data from the AF Frontier Ablation Registry and SAKURA AF Registry.

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8 months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71-1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49-0.94) and had a CHA2DS2-VASc score < 3 (HR 0.66 [vs. CHA2DS2-VASc score ≥ 3], 95% CI 0.43-0.98]). The 2-year risk reduction achieved by ablation may be small among Japanese patients, but AF ablation may benefit those with paroxysmal AF and a CHA2DS2-VASc score < 3.

Clinical Outcomes of Off-Label Underdosing of Direct Oral Anticoagulants After Ablation for Atrial Fibrillation.

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA2DS2-VASc scores differed significantly between DOAC dosing regimens, with patients given an appropriate standard-dose being significantly younger (63.3 ± 9.4 versus 64.8 ± 9.5 versus 73.2 ± 6.8 years, P < 0.0001) and lower (2.1 ± 1.5 versus 2.4 ± 1.6 versus 3.4 ± 1.4, P < 0.0001) than those given an off-label under-dose or an appropriate low-dose. During the median 19.0-month follow-up period, the AF recurrence rate was similar between the appropriate standard-dose and off-label under-dose groups but relatively low in the appropriate low-dose group (42.5% versus 41.2% versus 35.4%, P = 0.08). Annualized rates of thromboembolic events, major bleeding, and death from any cause were 0.47%, 0.70%, and 0.23% in the off-label under-dose group, while those rates were 0.74%, 0.73%, and 0.65% in the appropriate standard-dose, and 1.58%, 2.12%, and 1.57% in the appropriate low-dose groups.In conclusion, the clinical adverse event rates for patients on an off-label under-dose DOAC regimen after ablation, predicated on careful patient evaluations, was not high as seen with that of patients on a standard DOAC dosing regimen.

Current Status and Clinical Outcomes of Oral Anticoagulant Discontinuation After Ablation for Atrial Fibrillation in Japan　- Findings From the AF Frontier Ablation Registry.

BACKGROUND: The safety of discontinuing oral anticoagulant (OAC) after ablation for atrial fibrillation (AF) in Japanese patients has not been clarified.Methods and Results:A study based on the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) was conducted. Data were collected from 3,451 consecutive patients (74.1% men; age, 63.3±10.3 years) who had undergone AF ablation at any of 24 cardiovascular centers in Japan between August 2011 and July 2017. During a 20.7-month follow-up period, OAC therapy was discontinued in 1,836 (53.2%) patients; 51 patients (1.5%) suffered a stroke/transient ischemic attack (TIA), 71 (2.1%) suffered major bleeding, and 36 (1.0%) died. Patients in whom OAC therapy was discontinued were significantly younger than those in whom OACs were continued, and their CHA2DS2-VASc scores were significantly lower. The incidences of stroke/TIA, major bleeding, and death were significantly lower among these patients. Upon multivariate adjustment, stroke events were independently associated with relatively high baseline CHA2DS2-VASc scores but not with OAC status. CONCLUSIONS: Although the incidences of stroke/TIA, major bleeding, and death were relatively low among patients for whom OAC therapy was discontinued, stroke/TIA occurrence was strongly associated with a high baseline stroke risk rather than with OAC status. Thus, discontinuation of OAC therapy requires careful consideration, especially in patients with a high baseline stroke risk.

Safety and Efficacy of Subcutaneous Cardioverter Defibrillator in Patients at High Risk of Sudden Cardiac Death　- Primary Japanese Experience.

BACKGROUND: The entirely subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced as a new alternative to conventional transvenous ICD (TV-ICD) in Japan in February 2016, but its safety and efficacy are unclear.Methods and Results:A total of 60 patients (48 men, median age, 60 years; IQR, 44-67 years; primary prevention, n=24) underwent S-ICD implantation between February 2016 and August 2017. The device pocket was formed in the intermuscular space between the serratus anterior muscle and the latissimus dorsi muscle, and the parasternal S-ICD lead was placed according to pre-implant screening. Defibrillation test was performed in 56 patients (93%). Ventricular fibrillation (VF) was induced in 55 patients and terminated by a single 65-J shock in all patients. The median time to shock therapy was 13.4 s (IQR, 12.1-14.9 s) and the median post-shock impedance of the S-ICD lead was 64 Ω (IQR, 58-77 Ω). There were no operation-related complications or subsequent infectious complications. During follow-up (median, 275 days; IQR, 107-421 days), 1 patient (1.7%) had appropriate shock for VF with successful termination, whereas 5 patients (8.3%) had inappropriate shock due to oversensing of myopotential (n=3) or T-wave (n=1), and detection of supraventricular tachycardia (n=1). CONCLUSIONS: S-ICD is a safe and effective alternative to conventional TV-ICD. The long-term safety and efficacy of the S-ICD need further investigation.

Left atrial electrophysiologic feature specific for the genesis of complex fractionated atrial electrogram during atrial fibrillation.

Complex fractionated atrial electrogram (CFAE) has been suggested to contribute to the maintenance of atrial fibrillation (AF). However, electrophysiologic characteristics of the left atrial myocardium responsible for genesis of CFAE have not been clarified. Non-contact mapping of the left atrium was performed at 37 AF onset episodes in 24 AF patients. Electrogram amplitude, width, and conduction velocity were measured during sinus rhythm, premature atrial contraction (PAC) with long- (L-PAC), short- (S-PAC) and very short-coupling intervals (VS-PAC). These parameters were compared between CFAE and non-CFAE regions. Unipolar electrogram amplitude was higher in CFAE than non-CFAE during sinus rhythm, L-, S- and VS-PAC (1.82 ± 0.73 vs. 1.13 ± 0.38, p < 0.001; 1.44 ± 0.54 vs. 0.92 ± 0.35, p < 0.001; 1.09 ± 0.40 vs. 0.70 ± 0.27, p < 0.001; 0.76 ± 0.30 vs. 0.53 ± 0.25 mV, p < 0.001). Laplacian bipolar electrogram amplitude was also higher in CFAE than non-CFAE during sinus rhythm, L-, S- and VS-PAC. Unipolar electrogram width was similar in CFAE and non-CFAE. Laplacian bipolar electrogram width was wider in CFAE than non-CFAE during L-, S- and VS-PAC (85.5 ± 6.8 vs. 79.6 ± 4.5, p < 0.001; 96.1 ± 9.7 vs. 84.5 ± 5.9, p < 0.001; 122.4 ± 16.0 vs. 99.6 ± 9.6 ms, p < 0.001), but not during sinus rhythm. The conduction velocity was slower in CFAE during sinus rhythm, L-, S- and VS-PAC than non-CFAE (1.7 ± 0.3 vs. 2.4 ± 0.4, p < 0.001; 1.4 ± 0.3 vs. 2.0 ± 0.5, p < 0.001; 1.2 ± 0.3 vs. 1.7 ± 0.5, p < 0.001; and 0.9 ± 0.3 vs. 1.4 ± 0.4 m/s, p < 0.001). CFAE was generated in the high amplitude atrial myocardium with slow and non-uniform conduction properties which were pronounced associated with premature activation, suggesting that heterogeneous conduction produced in high amplitude region contributes to the genesis of CFAE.

Electrophysiologic mechanism of typical atrial flutter termination by nifekalant: effect of a pure IKr -selective blocking agent.

BACKGROUND: Little is known about the effect of nifekalant, a pure I(Kr) -selective blocker, on typical atrial flutter (AFL) and its termination mechanism. METHODS: The effects of nifekalant on AFL were elucidated in 17 patients. During AFL, the conduction time from the lateral to septal cavotricuspid isthmus (IS) and that through the reminder of the right atrium (nIS); AFL-cycle length (CL) variability, which was quantified by the standard deviation; and the maximum difference in AFL-CL were measured before and after administration of nifekalant (0.2-0.3 mg/kg). A single extrastimulus was delivered from the lateral cavotricuspid isthmus to elucidate the resetting response curves and atrial effective refractory period (AERP) before and after administration of nifekalant. RESULTS: There was no significant difference in AFL-CL, IS, and nIS before and after nifekalant; however, AERP was increased after nifekalant (155 ± 22 ms vs 184 ± 32 ms, P < 0.001). The standard deviation and the maximum difference in AFL-CL were both increased after nifekalant (1.7 ± 0.7 ms vs 3.6 ± 2.3 ms, P < 0.001 and 4.1 ± 1.9 ms vs 8.5 ± 5.2 ms, P < 0.001). The total excitable gap decreased (94 ± 17 ms vs 66 ± 21 ms, P < 0.001) with rightward shift of the resetting response curves and loss of full excitability after nifekalant. In 11 patients (65%), AFL was terminated spontaneously (n = 7) or by a single extrastimulus (n = 4), which was not observed before nifekalant. Termination was associated with orthodromic block in the cavotricuspid isthmus in all patients. CONCLUSIONS: Nifekalant increases AERP and AFL-CL variability by abolishing a fully excitable gap, without prolongation of AFL-CL. These unique effects facilitate the termination of AFL.

Initial multicenter clinical experience with the first-generation endoscopic guided laser balloon in Japan.

BACKGROUND: Isolation of the pulmonary veins (PVs) is the golden standard for atrial fibrillation (AF) ablation. To achieve a permanent PV isolation, the endoscopic guided HeartLight laser balloon system was invented. We analyzed the safety and efficacy of this laser balloon system. METHODS AND RESULTS: Three hundred four patients from 21 investigational sites inside Japan were enrolled in this study. One thousand sixty-two out of 1175 PVs (90.4%) were isolated using the HeartLight laser balloon. The isolation rate of the left superior, left inferior, right superior, and right inferior PVs was 87.8%, 91.3%, 91.6%, and 92.1%, respectively. The procedure time, defined as the time from the venous access to taking out the balloon, was 155 ± 39 min. The fluoroscopic time was 44 ± 25 min. The mean follow-up period was 309 ± 125 days. The freedom from AF recurrence at 3 months was 89.0% and at 12 months 82.1%. Adverse events occurred in 22 patients (7.2%) including phrenic nerve injury lasting more than 3 months in 1.6% and strokes in 1.0% of the patients. CONCLUSIONS: This initial experience demonstrated that the laser balloon ablation was feasible for PV isolation in Japanese AF patients.

Registry for Evaluating Healthy Life Expectancy and Long-Term Outcomes after Catheter Ablation of Atrial Fibrillation in the Very Elderly (REHEALTH AF) study: rationale and design of a prospective, multicentre, observational, comparative study.

INTRODUCTION: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes. METHODS AND ANALYSIS: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results. ETHICS AND DISSEMINATION: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000047023.

Feasibility evaluation of a remote monitoring system for implantable cardiac devices in Japan.

The number of implanted cardiac devices has been growing steadily over the last several years. Systems to monitor device data remotely have been introduced with the goal of reducing follow-up burden for both patients and physicians. Since the introduction of telemedicine depends greatly on the situations that are unique to each country, the acceptance of cardiac device remote monitoring in Japan was analyzed.A total of 203 patients who had previously undergone cardiac device implantation were enrolled. The subjects were provided with a CareLink Monitor that performed interrogation and transmission of device data at home, and then the physicians reviewed the data via a website at one and 3 months after baseline visits. A total of 470 transmissions were made. Questionnaires were completed by subjects and physicians to evaluate acceptance, ease of use, and satisfaction with the system. More than 87% of the subjects felt the Monitor was easy to use and nearly all of the physicians were satisfied with the system. A majority of patients felt reassured by having their devices assessed from a remote location and preferred the decreased number of clinic visits that were possible when using the Monitor. The patients spent an average of 168.2 minutes per clinic visit, whereas follow-up time was reduced to 13.0 minutes by remote monitoring. Physician consultation time was reduced by 2.7 minutes.The CareLink Network was well accepted by both the patients and physicians. Underlying issues did emerge, but once they are overcome, the system appears to have great potential to improve the quality of care given by healthcare providers.

Ablation Index-Guided High-Power Radiofrequency Application Shortens the Procedure Time With Similar Outcomes to Conventional Power Application in Atrial Fibrillation Ablation.

Background: The impact of high-power radiofrequency (RF) application in ablation index (AI)-guided atrial fibrillation (AF) ablation has not been elucidated. Methods and Results: We investigated 1,333 patients undergoing first AF ablation (median age 68 years; interquartile range [IQR] 61-73 years). The first 301 patients underwent AI-guided conventional power RF application (CP group), whereas the following 1,032 patients underwent high-power RF application (HP group). The minimum AI target values were 400, 360, and 260 at the left atrial anterior wall, posterior wall, and esophagus, respectively. RF power in the CP group was 30-40, 20-25, and 20 W at the anterior wall, posterior wall, and esophagus, respectively, compared with 50, 40, and 25, respectively, in the HP group. Procedure time was shorter in the HP than CP group (median 153 [IQR 129-190] vs. 180 (IQR 152-229) min; P<0.0001). The percentage of first-pass pulmonary vein isolation (69% vs. 73%; P=0.07) and all procedure-related complications (2.0% vs. 3.4%; P=0.19) was similar. Kaplan-Meier analysis showed similar recurrence-free survival (RFS) for all AF types. Respective 1-year RFS in the CP and HP groups was 82% and 87% in paroxysmal AF, 78% and 82% in persistent AF, and 59% and 58% in long-standing persistent AF. Conclusions: In AI-guided AF ablation, high-power RF application shortens the procedure time without increasing complications and with similar outcomes.

Analysis for the primary predictive factor for the incidence of esophageal injury after ablation of atrial fibrillation.

BACKGROUND: Esophageal injury (EI) is a serious complication that occurs after catheter ablation of atrial fibrillation (AF), however predictable factor of EI is unclear. METHODS: Among 308 patients who underwent AF ablation, upper gastrointestinal tract endoscopy was performed the next day after ablation to examine for EI. To define the primary factor that predicts EI, patients' characteristics, number and amount of radiofrequency energy applied to the posterior wall, ablation procedure, and the shortest distance between esophagus and posterior left atrium measured on contrast computed tomography (SD-CT) were analyzed. RESULTS: EI was found in 27 patients (8.8%). There were no significant differences in the patient characteristics, number and amount of radiofrequency energy applied to posterior wall or ablation procedure between patients with (Injury Group) and without EI (Non-Injury Group). However, SD-CT in the Injury Group was significantly shorter than that in Non-Injury Group (2.3±0.6mm vs 4.1±0.9mm, p<0.001). The area under a receiver operating characteristic curve using SD-CT as a predictive marker in EI patients was 0.988 (p<0.001). When the cut-off value of SD-CT was set at 2.9mm, the sensitivity and specificity for EI diagnosis were 92.3% and 96.8%, and the positive predictive value and negative predictive value were 0.75 and 0.99, respectively. CONCLUSIONS: EI observed after catheter ablation of AF was closely associated with the SD-CT. Patients with SD-CT below 2.9mm have a potential risk of EI and thus must be strictly followed.

Importance of pericardial fat in the formation of complex fractionated atrial electrogram region in atrial fibrillation.

BACKGROUND/OBJECTIVES: Pericardial fat (PF) and complex fractionated atrial electrogram (CFAE) are both associated with atrial fibrillation (AF). Therefore, we examined the relation between PF and CFAE area in AF. METHODS: The study population included 120 control patients without AF and 120 patients with AF (80 paroxysmal AF and 40 persistent AF) who underwent catheter ablation. Total cardiac PF volume, representing all adipose tissue within the pericardial sac, was measured by contrast-enhanced computed tomography. The location and distribution of CFAE region were identified by left atrial endocardial mapping using a three-dimensional mapping system. We analyzed the significance of total cardiac PF volume and total area of CFAE region on AF, persistence of AF from paroxysmal to persistent form, and the relation between total cardiac PF volume and total CFAE area. We also evaluated the regional distribution of PF volume and CFAE area in five areas of the left atrium (LA). RESULTS: Total cardiac PF volume correlated with AF (odds ratio [OR]: 1.024, p<0.001). Total cardiac PF volume and total CFAE area were both independently associated with persistence of AF (OR: 1.018, p=0.018, OR: 1.144, p=0.002, respectively). Multivariate linear regression analysis identified total cardiac PF volume as a significant and independent determinant of total CFAE area (r=0.488, p<0.001). Furthermore, regional PF volume correlated with local CFAE area in an each LA area. CONCLUSIONS: PF volume correlated significantly with CFAE area in patients with AF. This finding suggests that PF is directly related to the progression of CFAE area and promotes the pathogenic process of AF.

Demonstration of anatomic reentrant circuit in verapamil-sensitive atrial tachycardia originating from the atrioventricular annulus other than the vicinity of the atrioventricular node.

The mechanism and tachycardia circuit of verapamil-sensitive atrial tachycardia originating from the atrioventricular annulus (AVA-AT) other than the atrioventricular node vicinity are not well clarified. In 23 patients, we examined the mechanism and anatomic tachycardia circuit of AVA-AT. While recording the atrial electrogram at the earliest atrial activation site (EAAS) during tachycardia, rapid atrial pacing at a rate 5 beats/min faster than the tachycardia rate was delivered from multiple sites of the right atrium (RA) to demonstrate manifest entrainment and define the direction of proximity of slow conduction area (SCA) of reentry circuit. When EAAS was orthodromically captured, radiofrequency energy was delivered starting at a site 2 cm away from the EAAS in the direction of entrainment pacing site. Then application site was gradually advanced toward the EAAS until termination of tachycardia to define the entrance of SCA of reentry circuit. Manifest entrainment was demonstrated in all AVA-ATs. The EAAS, distributed along the tricuspid annulus from 3- to the 12-o'clock position, was orthodromically captured by pacing delivered from high anterolateral RA (n = 6), high anteroseptal RA (n = 7), high posteroseptal RA (n = 3), low anterolateral RA (n = 6), and coronary sinus ostium (n = 1). Radiofrequency energy delivery to the site, 10.4 ± 2.4 mm proximal to the EAAS where the atrial electrogram was observed 13.9 ± 5.7 ms later than the EAAS, terminated AVA-AT immediately after the onset of energy delivery (2.9 ± 1.1 seconds). In conclusion, it was shown that the AVA-AT is organized as reentry involving the verapamil-sensitive SCA with its entrance and exit at different distinct locations.