Characteristics of tissue temperature during ablation with THERMOCOOL SMARTTOUCH SF versus TactiCath versus QDOT MICRO catheters (Qmode and Qmode+): An in vivo porcine study.

INTRODUCTION: High-power short-duration (HPSD) ablation at 50 W, guided by ablation index (AI) or lesion size index (LSI), and a 90 W/4 s very HSPD (vHPSD) setting are available for atrial fibrillation (AF) treatment. Yet, tissue temperatures during ablation with different catheters around venoatrial junction and collateral tissues remain unclear. METHODS: In this porcine study, we surgically implanted thermocouples on the epicardium near the superior vena cava (SVC), right pulmonary vein, and esophagus close to the inferior vena cava. We then compared tissue temperatures during 50W-HPSD guided by AI 400 or LSI 5.0, and 90 W/4 s-vHPSD ablation using THERMOCOOL SMARTTOUCH SF (STSF), TactiCath ablation catheter, sensor enabled (TacthCath), and QDOT MICRO (Qmode and Qmode+ settings) catheters. RESULTS: STSF produced the highest maximum tissue temperature (Tmax ), followed by TactiCath, and QDOT MICRO in Qmode and Qmode+ (62.7 ± 12.5°C, 58.0 ± 10.1°C, 50.0 ± 12.1°C, and 49.2 ± 8.4°C, respectively; p = .005), achieving effective transmural lesions. Time to lethal tissue temperature ≥50°C (t-T ≥ 50°C) was fastest in Qmode+, followed by TacthCath, STSF, and Qmode (4.3 ± 2.5, 6.4 ± 1.9, 7.1 ± 2.8, and 7.7 ± 3.1 s, respectively; p < .001). The catheter tip-to-thermocouple distance for lethal temperature (indicating lesion depth) from receiver operating characteristic curve analysis was deepest in STSF at 5.2 mm, followed by Qmode at 4.3 mm, Qmode+ at 3.1 mm, and TactiCath at 2.8 mm. Ablation at the SVC near the phrenic nerve led to sudden injury at t-T ≥ 50°C in all four settings. The esophageal adventitia injury was least deep with Qmode+ ablation (0.4 ± 0.1 vs. 0.8 ± 0.4 mm for Qmode, 0.9 ± 0.3 mm for TactiCath, and 1.1 ± 0.5 mm for STSF, respectively; p = .005), correlating with Tmax . CONCLUSION: This study revealed distinct tissue temperature patterns during HSPD and vHPSD ablations with the three catheters, affecting lesion effectiveness and collateral damage based on Tmax and/or t-T ≥ 50°C. These findings provide key insights into the safety and efficacy of AF ablation with these four settings.

In vivo tissue temperatures during 90 W/4 sec-very high power-short-duration (vHPSD) ablation versus ablation index-guided 50 W-HPSD ablation: A porcine study.

INTRODUCTION: Neither the actual in vivo tissue temperatures reached with 90 W/4 s-very high-power short-duration (vHPSD) ablation for atrial fibrillation nor the safety and efficacy profile have been fully elucidated. METHODS: We conducted a porcine study (n = 15) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures close to a QDOT MICRO catheter, between during 90 W/4 s-vHPSD ablation during ablation index (AI: target 400)-guided 50 W-HPSD ablation, both targeting a contact force of 8-15 g. RESULTS: Maximum tissue temperature reached during 90 W/4 s-vHPSD ablation did not differ significantly from that during 50 W-HPSD ablation (49.2 ± 8.4°C vs. 50.0 ± 12.1°C; p = .69) and correlated inversely with distance between the catheter tip and the thermocouple, regardless of the power settings (r = -0.52 and r = -0.37). Lethal temperature (≥50°C) was best predicted at a catheter tip-to-thermocouple distance cut-point of 3.13 and 4.27 mm, respectively. All lesions produced by 90 W/4 s-vHPSD or 50 W-HPSD ablation were transmural. Although there was no difference in the esophageal injury rate (50% vs. 66%, p = .80), the thermal lesion was significantly shallower with 90 W/4 s-vHPSD ablation than with 50W-HPSD ablation (381.3 ± 127.3 vs. 820.0 ± 426.1 µm from the esophageal adventitia; p = .039). CONCLUSION: Actual tissue temperatures reached with 90 W/4 s-vHPSD ablation appear similar to those with AI-guided 50 W-HPSD ablation, with the distance between the catheter tip and target tissue being shorter for the former. Although both ablation settings may create transmural lesions in thin atrial tissues, any resulting esophageal thermal lesions appear shallower with 90 W/4 s-vHPSD ablation.

In vivo tissue temperature during lesion size index-guided 50W ablation versus 30W ablation: A porcine study.

BACKGROUND: Neither the actual in vivo tissue temperatures reached with lesion size index (LSI)-guided high-power short-duration (HPSD) ablation for atrial fibrillation nor the safety profile has been elucidated. METHODS: We conducted a porcine study (n = 7) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures reached during 50 W-HPSD ablation with those reached during standard (30 W) ablation, both targeting an LSI of 5.0 (5-15 g contact force). RESULTS: Tmax  (maximum tissue temperature when the thermocouple was located ≤5 mm from the catheter tip) reached during HPSD ablation was modestly higher than that reached during standard ablation (58.0 ± 10.1°C vs. 53.6 ± 9.2°C; p = .14) and peak tissue temperature correlated inversely with the distance between the catheter tip and the thermocouple, regardless of the power settings (HPSD: r = -0.63; standard: r = -0.66). Lethal temperature (≥50°C) reached 6.3 ± 1.8 s and 16.9 ± 16.1 s after the start of HPSD and standard ablation, respectively (p = .002), and it was best predicted at a catheter tip-to-thermocouple distance cut point of 2.8 and 5.3 mm, respectively. All lesions produced by HPSD ablation and by standard ablation were transmural. There was no difference between HPSD ablation and standard ablation in the esophageal injury rate (70% vs. 75%, p = .81), but the maximum distance from the esophageal adventitia to the injury site tended to be shorter (0.94 ± 0.29 mm vs. 1.40 ± 0.57 mm, respectively; p = .09). CONCLUSIONS: Actual tissue temperatures reached with LSI-guided HPSD ablation appear to be modestly higher, with a shorter distance between the catheter tip and thermocouple achieving lethal temperature, than those reached with standard ablation. HPSD ablation lasting <6 s may help minimize lethal thermal injury to the esophagus lying at a close distance.

Actual tissue temperature during ablation index-guided high-power short-duration ablation versus standard ablation: Implications in terms of the efficacy and safety of atrial fibrillation ablation.

BACKGROUND: Actual in vivo tissue temperatures and the safety profile during high-power short-duration (HPSD) ablation of atrial fibrillation have not been clarified. METHODS: We conducted an animal study in which, after a right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We recorded tissue temperatures during a 50 W-HPSD ablation and 30 W-standard ablation targeting an ablation index (AI) of 400 (5-15 g contact force). RESULTS: Maximum tissue temperatures reached with HSPD ablation were significantly higher than that reached with standard ablation (62.7 ± 12.5 vs. 52.7 ± 11.4°C, p = 0.033) and correlated inversely with the distance between the catheter tip and thermocouple, regardless of the power settings (HPSD: r = -0.71; standard: r = -0.64). Achievement of lethal temperatures (≥50°C) was within 7.6 ± 3.6 and 12.1 ± 4.1 s after HPSD and standard ablation, respectively (p = 0.003), and was best predicted at cutoff points of 5.2 and 4.4 mm, respectively. All HPSD ablation lesions were transmural, but 19.2% of the standard ablation lesions were not (p = 0.011). There was no difference between HPSD and standard ablation regarding the esophageal injury rate (30% vs. 33.3%, p > 0.99), with the injury appearing to be related to the short distance from the catheter tip. CONCLUSIONS: Actual tissue temperatures reached with AI-guided HPSD ablation appeared to be higher with a greater distance between the catheter tip and target tissue than those with standard ablation. HPSD ablation for <7 s may help prevent collateral tissue injury when ablating within a close distance.

Clinical significance of the albumin-bilirubin score in patients with heart failure undergoing cardiac resynchronization therapy.

Despite emerging recognition of interactions between heart failure (HF) and liver dysfunction, the impact of cardiac hepatopathy on patients with HF undergoing cardiac resynchronization therapy (CRT) has not been fully elucidated. Albumin-bilirubin (ALBI) score is a new assessment of liver function. The relationship between liver dysfunction severity based on ALBI score and clinical outcomes of patients with HF receiving CRT is unclear. Clinical records of 274 patients who underwent CRT device implantation between March 2003 and October 2020 were retrospectively investigated. ALBI score was calculated based on serum albumin and total bilirubin levels obtained before CRT device implantation. Patients were divided into three groups based on ALBI score: first tertile (ALBI ≤ - 2.62, n = 91)), second tertile (- 2.62 < ALBI < - 2.13, n = 92), and third tertile (ALBI ≥ - 2.13, n = 91). The study endpoint was all-cause mortality. The third tertile group had more advanced NYHA functional class, lower hemoglobin levels, and higher total bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and N-terminal Pro-B-type natriuretic peptide levels (all p < 0.05). The third tertile group also had a higher prevalence of moderate or severe tricuspid regurgitation and higher tricuspid regurgitation pressure gradient (all p < 0.05). CRT response rates were significantly lower in the third tertile group. During a median (interquartile range) follow-up of 30 (9-60) months, 104 (37.9%) patients died. The third tertile group had significantly higher rates of all-cause mortality (log-rank p < 0.001). Higher ALBI score was significantly associated with all-cause mortality, even after adjusting for clinically relevant factors, a conventional validated risk score, and echocardiographic parameters related to right HF (all p < 0.01). Higher ALBI score before CRT device implantation is associated with HF severity, hepatic congestion and impairment due to right HF, lower CRT response, and higher all-cause mortality in CRT recipients.

Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome.

AIMS: The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability. METHODS AND RESULTS: Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves. CONCLUSION: In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.

Effect of obesity and epicardial fat/fatty infiltration on electrical and structural remodeling associated with atrial fibrillation in a novel canine model of obesity and atrial fibrillation: A comparative study.

BACKGROUND: How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. METHODS: To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. RESULTS: Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p < .05). Epicardial fat/Fatty infiltration was greatest in the Obese-RAP group, and greater in the Obese and RAP groups than in the Control group. %interstitial fibrosis/fibrosis-related gene expression was significantly greater in the Obese-RAP and RAP groups (p < .05). CONCLUSIONS: Vulnerability to AF was associated with increased LA pressure and increased epicardial fat/fatty infiltration in our Obese group, and with increased epicardial fat/fibrofatty infiltration in the RAP and Obese-RAP groups. These may explain the role of obesity/epicardial fat in the pathogenesis of AF.

Impact of the combined use of intracardiac ultrasound and a steerable sheath visualized by a 3D mapping system on pulmonary vein isolation.

BACKGROUND: A novel steerable sheath visualized on a three-dimensional mapping system has become available in this era in which a durable pulmonary vein (PV) isolation (PVI) with reduced fluoroscopy is required. METHODS: In 60 patients who underwent a PVI with a visualized sheath (n = 30) and non-visualized conventional sheath (n = 30), the fluoroscopic time and catheter stability during the PVI were analyzed. RESULTS: The fluoroscopic time during the transseptal access (0 [0, 0.1] vs. 1.4 [0.8, 2.3] minutes, P < .001) and PVI (0 [0, 0.1] vs. 0.4 [0.2, 1.1] minutes, P < .001) were shorter in the visualized sheath group than conventional sheath group. The procedure time during the PVI (32.0 [26.8, 36.3] vs. 41.0 [31.8, 47.3] minutes, P = .01), particularly during the right PVI (15.0 [12.8, 18.0] vs. 23.0 [15.8, 26.3] minutes, P = .009), was shorter in the visualized sheath group than conventional sheath group, however, that during the other steps was equivalent. The standard deviation of the catheter contact force during each radiofrequency application was smaller in the visualized sheath group than conventional sheath group (4.5 ± 2.7 vs. 4.9 ± 3.1 g, P = .001). The impedance drop for each lesion was larger in the visualized sheath group than conventional sheath group (10.7 ± 6.5 vs. 9.8 ± 5.5 ohms, P < .001). The incidence of acute PV reconnections per patient (30% vs. 23%, P = .56) and per PV segment (2.5% vs. 2.3%, P = .83) were similar between the two groups. No major complications occurred in either sheath group. CONCLUSIONS: The use of visualized sheaths may reduce the fluoroscopic time and improve the catheter stability during the PVI.

Narrower QRS may be enough to respond to cardiac resynchronization therapy in lightweight patients.

A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men's and women's BSA values were 1.74 m2 and 1.48 m2 in the controls (p < 0.0001), and 1.70 m2 and 1.41 m2 in the CRT patients (p < 0.0001). The men's and women's QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.

Benefit of Rate Response with Closed-Loop Stimulation in Patients with Difficult Hemodialysis.

Rate-responsive pacing is known to improve quality of life (QOL) in patients with sick sinus syndrome and chronotropic incompetence. However, the sensors for rate response include accelerometers, closed-loop stimulation (CLS), and minute ventilation sensors (MV sensors), each of which has a different mode of action. For this reason, it is important to select appropriate sensors that match the daily habits and behavioral patterns of the patient. For example, young and active patients are expected to have a rate increase when an accelerometer is used, while elderly patients and patients with a physical disability who are only able to move slowly often have a poor response to the accelerometer. MV sensors are therefore better suited to these patients. Furthermore, CLS is considered effective for patients who require an increase in heart rate when at rest, for example, patients undergoing maintenance dialysis.We describe a representative case, demonstrating the effectiveness of closed-loop stimulation in a patient with hypotension during dialysis.

Prognostic Value of Serum N-Terminal Pro-Brain Natriuretic Peptide Level over Heart Failure for Stroke Events and Deaths in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) and heart failure (HF) often coexist. The aims of this study were to explore the factors associated with the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the association between prognosis and a history of HF or the serum NT-proBNP level in Japanese patients with AF.The present sub-study was based on the SAKURA AF Registry, a Japanese multicenter observational registry that included 3267 AF patients (median follow-up period: 39 months). All the patients were receiving warfarin or any of four direct oral anticoagulants. Serum NT-proBNP levels were available for 2417 patients, and the median value was 508 (interquartile range 202-1095) pg/mL at the time of enrollment. Log NT-proBNP was associated with non-paroxysmal AF, creatinine clearance > 60 mL/minute, history of HF and ischemic heart disease, antiarrhythmic drug use, anemia, being elderly female, and history of AF ablation. The relative risk of adverse clinical events, except major bleeding, was significantly higher in the highest NT-proBNP quartile as compared to the lowest quartile (adjusted hazard ratios: 2.87 for death, 2.39 for stroke), but a history of HF was associated only with a higher incidence of all-cause death.Concomitant HF was associated with a higher mortality, but the high NT-proBNP was associated with higher mortality and stroke events. In Japanese AF patients receiving anticoagulant treatment, high serum NT-proBNP levels predict the risk for both stroke events and deaths, and intensive follow-up is needed in such patients.

Electrophysiologic and anatomic factors predictive of a need for touch-up radiofrequency application for complete pulmonary vein isolation: Comparison between hot balloon- and cryoballoon-based ablation.

INTRODUCTION: Although electrophysiologic and anatomic factors associated with the need for touch-up radiofrequency (RF) applications after cryoballoon ablation (CBA) for atrial fibrillation (AF) have been well described, those associated with the need for such touch-up after hot balloon ablation (HBA) have not. We aimed to identify factors predictive of the need for touch-up applications following HBA. METHODS: Anatomic and electrophysiologic factors predictive of the need for touch-up RF ablation were compared between 46 propensity score-matched pairs of patients who underwent HBA or CBA for AF. RESULTS: Touch-up RF ablation was more frequently required after HBA than after CBA (57% vs 30%, respectively; P = .01), and mostly at the anterior aspect of the left superior pulmonary vein (LSPV) carina after HBA (35%) but at the inferior aspect of the right inferior PV (RIPV) after CBA (71%). Post HBA touch-up was associated with male gender, a CHA 2 DS 2 -VASc score ≤ 2, PV-left atrial bipolar voltage ≥ 1.35 mV, and PV trunk length ≥ 24.0 mm; post CBA touch-up associated with a history of heart failure. CONCLUSION: Following balloon ablation for AF, there may be a need for touch-up applications, especially at the LSPV ridge after HBA but at the RIPV after CBA. It may behoove operators to expect a need for touch-up following HBA when patients are male, have a CHA2 DS 2 -VASc score ≤ 2 points, when PV-LA bipolar voltage is ≥ 1.35 mV, or when the PV trunk is ≥ 24.0 mm or following CBA when there is a history of heart failure.

Oral anticoagulant use and clinical outcomes in elderly Japanese patients: findings from the SAKURA AF Registry.

Direct-acting oral anticoagulants (DOACs) are widely used in aged Japanese patients with atrial fibrillation (AF), but outcome data for such patients are limited. We compared outcomes between 1895 (58.5%) patients aged < 75 years (non-elderly), 1078 (33.3%) 75-84 years (elderly) and 264 (8.2%) ≥ 85 years (very elderly) enrolled in a prospective multicenter registry. Kaplan-Meier analysis (median follow-up: 39.3 months) revealed a significantly high incidence of stroke/systemic embolism (SE) among the very elderly relative to that among the non-elderly or elderly (3.2 vs. 1.2 and 1.5 events per 100 patient-years, p < 0.001). Major bleeding in the non-elderly group was significantly infrequent relative to that among the elderly or very elderly group (1.1 vs. 1.6 vs. 1.8 events, p = 0.033). After multivariate adjustment, the stroke/SE incidence was comparable between DOAC and warfarin users, regardless of age, but major bleeding decreased significantly among very elderly DOAC users (adjusted HR 0.220, 95% CI 0.042-0.920). The greater increasing incidence of stroke/SE than major bleeding as patients age suggests that stroke prevention should outweigh the bleeding risk when anticoagulants are being considered for aged patients. Our data indicated that DOACs can be a therapeutic option for stroke prevention in very elderly patients.

Adverse Clinical Events during Long-Term Follow-Up After Catheter Ablation of Atrial Fibrillation.

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.

Impact of Sinus Node Recovery Time after Long-Standing Atrial Fibrillation Termination on the Long-Term Outcome of Catheter Ablation.

Atrial electrical and structural remodeling is related to the perpetuation of atrial fibrillation (AF) subsequent to sinus node dysfunction. We investigated the relationship between AF recurrence after catheter ablation and sinus node dysfunction in long-standing persistent AF patients using the sinus node recovery time (SNRT) after defibrillation.Fifty-one consecutive patients who underwent a first ablation for long-standing persistent AF were enrolled. Intracardiac cardioversion was applied before ablation in the absence of any antiarrhythmic drugs, and the power required to defibrillate, number, and SNRT after defibrillation were measured. All patients underwent the same designed radiofrequency catheter ablation procedure.No patient required permanent pacemaker implantation due to sinus dysfunction after the ablation. During the follow-up period of 28.4 months (3.6-43.7), 35 out of 51 patients (69%) experienced an AF recurrence. The AF recurrence was significantly associated with an older age (60 ± 11 versus 52 ± 12 years in the non-recurrence group, P = 0.0196), longer SNRT after defibrillation (1722 [1410-2656] versus 1295 [676-1651] msec, P = 0.0125), and larger left atrial (LA) volume (59 ± 25 versus 41 ± 15 mL, P = 0.0119). There were no significant differences in the AF duration, AF cycle length, and right and total atrial conduction times between the 2 groups. A longer SNRT after defibrillation (adjusted HR 2.13, 95%CI 1.16-3.71, P = 0.0152) and larger LA volume (adjusted HR 1.03, 95%CI 1.01-1.04, P = 0.0054) were independent predictors of AF recurrence after ablation.Assessment of the SNRT after defibrillation may help to predict a successful ablation in patients with long-standing persistent AF.

Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis.

BACKGROUND: The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain. METHODS AND RESULTS: We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden cardiac arrest who underwent programmed ventricular stimulation. We estimated incidence rates and relative hazards of cardiac arrest or implantable cardioverter-defibrillator shock. We analyzed individual-level data from 8 studies comprising 1312 patients who experienced 65 cardiac events (median follow-up, 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (hazard ratio, 2.66; 95% confidence interval [CI], 1.44-4.92, P<0.001), with the greatest risk observed among those induced with single or double extrastimuli. Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction. The lowest risk occurred in individuals without syncope and with drug-induced type 1 patterns (0.23%, 95% CI, 0.05-0.68 for no induced arrhythmia with up to double extrastimuli; 0.45%, 95% CI, 0.01-2.49 for induced arrhythmia), and the highest risk occurred in individuals with syncope and spontaneous type 1 patterns (2.55%, 95% CI, 1.58-3.89 for no induced arrhythmia; 5.60%, 95% CI, 2.98-9.58 for induced arrhythmia). CONCLUSIONS: In patients with Brugada syndrome, arrhythmias induced with programmed ventricular stimulation are associated with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk, particularly in patients with high-risk clinical features.

Ventriculoatrial Intervals ≤70 ms in Orthodromic Atrioventricular Reciprocating Tachycardia.

BACKGROUND: Although a ventriculoatrial interval (VAI) of ≤70 ms is used to distinguish atrioventricular nodal reentrant tachycardia from orthodromic atrioventricular reciprocating tachycardia (AVRT), a VAI of ≤70 ms is sometimes observed in cases of AVRT. The study aimed to evaluate the short VAI that is seen in AVRT and to understand its underlying mechanism. METHODS: Electrophysiologic studies of 46 consecutive patients with AVRT involving an accessory pathway (AP) were examined retrospectively. RESULTS: AP was right sided in seven patients and left sided in 39. A VAI (interval from QRS onset to the earliest intracardiac atrial electrogram recorded by any mapping catheter during AVRT) ≤70 ms during AVRT (short VAI) was observed in eight patients: six with a left lateral AP and two with a left posteroseptal AP. During AVRT involving a left-sided AP, the QRS-V interval (from the earliest QRS onset to the local ventricular electrogram at a site which showed earliest atrial electrogram recorded from the coronary sinus catheter) was significantly shorter (37 ± 7 ms vs 54 ± 13 ms, P = 0.001) and supernormal conduction (QRS duration or the QRS-V interval shortening by ≥10 ms during AVRT) was more frequently seen (63% vs 6%, P = 0.02) in the short VAI group than in the normal VAI group. Furthermore, these parameters were shown to be determinants for short VAI. CONCLUSIONS: A short VAI is sometimes observed during AVRT involving a left-sided AP. The short VAI may be caused by rapid propagation or supernormal conduction between the proximal Purkinje-muscle junction and basal left ventricular myocardium.

A nonsynonymous polymorphism in semaphorin 3A as a risk factor for human unexplained cardiac arrest with documented ventricular fibrillation.

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.

Difference Between Dormant Conduction Sites Revealed by Adenosine Triphosphate Provocation and Unipolar Pace-Capture Sites Along the Ablation Line After Pulmonary Vein Isolation.

Dormant pulmonary vein (PV) conduction revealed by adenosine/adenosine triphosphate (ATP) provocation test and exit block to the left atrium by pacing from the PV side of the ablation line ("pace and ablate" method) are used to ensure durable pulmonary vein isolation (PVI). However, the mechanistic relation between ATP-provoked PV reconnection and the unexcitable gap along the ablation line is unclear.Forty-five patients with atrial fibrillation (AF) (paroxysmal: 31 patients, persistent: 14 patients; age: 61.1 ± 9.7 years) underwent extensive encircling PVI (EEPVI, 179 PVs). After completion of EEPVI, an ATP provocation test (30 mg, bolus injection) and unipolar pacing (output, 10 mA; pulse width, 2 ms) were performed along the previous EEPVI ablation line to identify excitable gaps. Dormant conduction was revealed in 29 (34 sites) of 179 PVs (16.2%) after EEP-VI (22/45 patients). Pace capture was revealed in 59 (89 sites) of 179 PVs (33.0%) after EEPVI (39/45 patients), and overlapping sites, ie, sites showing both dormant conduction and pace capture, were observed in 22 of 179 (12.3%) PVs (17/45 patients).Some of the ATP-provoked dormant PV reconnection sites were identical to the sites with excitable gaps revealed by pace capture, but most of the PV sites were differently distributed, suggesting that the main underling mechanism differs between these two forms of reconnection. These findings also suggest that performance of the ATP provocation test followed by the "pace and ablate" method can reduce the occurrence of chronic PV reconnections.

Relation Between Left Atrial Wall Thickness in Patients with Atrial Fibrillation and Intracardiac Electrogram Characteristics and ATP-Provoked Dormant Pulmonary Vein Conduction.

INTRODUCTION: Atrial remodeling plays a key role in development of the substrate for atrial fibrillation (AF). Whether the wall thicknesses of the left atrium (LA) and pulmonary vein (PV)-LA junction affect remodeling and AF ablation is unknown. We investigated the relationship between wall thicknesses, electrogram characteristics, and adenosine triphosphate (ATP)-provoked dormant PV conduction as they pertain to AF. METHODS: In 50 patients with AF and 25 patients without AF, wall thicknesses of the LA and PV-LA junction were measured on 320-slice computed tomography images. For the AF patients, NavX-based voltage maps generated during sinus rhythm were obtained, and ATP-provoked dormant PV conduction after PV isolation was evaluated. RESULTS: Walls of the LA and PV-LA junction were significantly thicker in the AF patients than in the control patients (1.83 ± 0.29 mm vs. 1.59 ± 0.28 mm, respectively; P = 0.0010; and 0.88 ± 0.14 mm vs. 0.65 ± 0.11 mm, P<0.0001, respectively). Wall thickness at the PV-LA junction was independently associated with AF (ß = 0.40, P = 0.0002). In AF patients, the walls of the PV-LA junction showed stepwise thickening across bipolar voltages indicative of severe (bipolar voltage <33rd percentile) to moderate (33rd-66th percentiles) to mild fibrosis/scarring (≥66th percentile). Walls of the PV-LA junction with dormant PV conduction were significantly thicker than those without it (0.94 ± 0.19 mm vs. 0.86 ± 0.21 mm, respectively; P = 0.0025). CONCLUSIONS: Together, the association between thickened PV-LA junction walls and AF and the increased bipolar voltage suggests that such wall thickening increases PV electrical activities, leading to initiation and maintenance of AF and perhaps to ATP-provoked dormant PV conduction.