Efficacy and safety of a novel temperature-controlled catheter for cavotricuspid isthmus ablation.

BACKGROUND: Maintaining an adequate temperature at the target site is essential for effective ablation. We hypothesized that a tissue temperature-controlled (T-Con) catheter for cavotricuspid isthmus (CTI) ablation could improve the procedural ablation parameters. PURPOSE: To evaluate the efficacy and safety of the T-Con (DiamondTemp™) catheter for CTI ablation compared with non-irrigation (Non-Irri) and irrigation (Irri) catheters. METHODS: We analyzed 150 patients who underwent prophylactic CTI ablation combined with pulmonary vein isolation. The Non-Irri, Irri, and T-Con catheter groups comprised 50 patients each, and the ablation procedural parameters and complications were compared between these groups. RESULTS: There were no significant differences in clinical background characteristics among the three groups. The Kruskal-Wallis and post hoc tests demonstrated that the T-Con group showed the lowest total radiofrequency energy delivery time among the three groups (median [25 and 75 percentiles]: 340 [209, 357], 147 [100, 199], and 83 [61, 109] s, respectively in the Non-Irri, Irri, and T-Con groups; T-Con versus Non-Irri, p < .01; T-Con versus Irri, p < .01). The total procedural time and acute reconnection rate in the T-Con group (264 s and 4%, respectively) were lower than those in the Non-Irri group (438 s and 24%) but were similar to those in the Irri group (268 s and 6%). No significant complications were observed in any group. CONCLUSIONS: The T-Con catheter achieved a short energy delivery time and a low acute reconnection rate, indicating its potential as an alternative catheter for CTI ablation.

Borg's exertion scale did not coincide with ventilatory anaerobic threshold in atrial fibrillation patients with restored sinus rhythm after ablation.

The determination of precise exercise intensity is essential for effective exercise rehabilitation. The Borg rating of perceived exertion category ratio (CR) scale is utilized to prescribe an appropriate level of exertion intensity. A Borg CR of approximately 13 coincides with the ventilatory aerobic threshold (VAT). Patients with atrial fibrillation (AF) exhibit various symptoms. We hypothesized that the workload at Borg CR13 (Borg CR13-Watt) differs from the workload at the VAT level (VAT-Watt) in AF patients with restored sinus rhythm (SR) following ablation. Accordingly, the relationship between Borg CR13-Watt and VAT-Watt was studied in patients with restored SR. Cardiopulmonary exercise testing (CPET) was performed at 101±88 days after ablation in 150 patients using a bicycle ergometer. No adverse events were observed during CPET. Borg CR13-Watt was significantly higher than VAT-Watt (67.2±27.8 Watt vs. 54.7±17.6 Watt, P<0.0001). Borg CR13-Watt showed significant linear regression with VAT-Watt (regression coefficient, 0.49, P<0.01; correlation coefficient, 0.80, P<0.01). Higher Borg CR13-Watt was associated with greater differences between Borg CR13-Watt and VAT-Watt (ΔWatt). The Bland-Altman plot showed nonconcordance between the two. Male sex, use of antiarrhythmic drugs, and smoking had contributed to the increased ΔWatt. Duration from ablation to time of CPET did not correlate with ΔWatt. Therefore, Borg CR13-Watt did not coincide with VAT-Watt in patients with restored SR. Higher Borg CR13-Watt was associated with greater ΔWatt. Prescribing exertion intensity as determined solely by perceived exertion is inadequate. CPET is required to determine the precise exercise intensity in AF patients with restored SR after ablation.

Incidence of nausea/vomiting following propofol sedation with adaptive servo-ventilation for atrial fibrillation ablation.

Background: Postoperative nausea and vomiting (PONV) following atrial fibrillation (AF) ablation can cause considerable distress. Aim: Continuous intravenous propofol sedation with adaptive servo-ventilation (ASV) with or without an analgesic, pentazocine, during AF ablation was studied in 272 consecutive patients with paroxysmal, persistent, and long-standing persistent AF. The study objectives were to determine the incidence of PONV after AF ablation and to assess the predictive value of factors for PONV using the area under the receiver operating characteristic curve (AUC). Results: The present sedation maneuver was successfully accomplished with a low incidence of hypotension and without discontinuation of ablation or switching to general anesthesia, while maintaining an acceptable procedural time (102 ± 32 min). The incidence of PONV was 5.5% (15/272). Nausea occurred in nine patients after an average of 4.6 ± 3.5 h (range: 2-12 h) postablation, and vomiting with nausea occurred in six patients after an average of 4.5 ± 3.1 h (range: 1-9 h) postablation. The postablation interval did not differ significantly between the occurrence of nausea and nausea accompanied by vomiting. AUCs based on various factors, including the Apfel score, ranged from 0.55 to 0.67, indicating low accuracy in predicting PONV occurrence. Conclusions: The incidence of PONV after propofol sedation with ASV was the lowest (5.5%) reported to date. Scoring systems, which included the Apfel score, were ineffective in predicting PONV. The low PONV incidence in addition to the efficacy of propofol sedation with ASV revealed the adequacy of this regimen for AF ablation.

Radiofrequency Catheter Ablation for Atrial Fibrillation Patients on Hemodialysis (From the Kansai Plus Atrial Fibrillation Registry)　- Clinical Impact of Early Recurrence.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) in patients on hemodialysis (HD) is reported to have a high risk of late recurrence (LR). However, the relationship between early recurrence (ER) within a 90-day blanking period after CA in AF patients and LR in HD patients remains unclear. METHODS AND RESULTS: Of the 5,010 patients in the Kansai Plus Atrial Fibrillation Registry, 5,009 were included in the present study. Of these patients, 4,942 were not on HD (non-HD group) and 67 were on HD (HD group). HD was an independent risk factor for LR after the initial CA (adjusted hazard ratio 1.6; 95% confidence interval 1.1-2.2; P=0.01). In patients with ER, the rate of sinus rhythm maintenance at 3 years after the initial CA was significantly lower in the HD than non-HD group (11.4% vs. 35.4%, respectively; log-rank P=0.004). However, in patients without ER, there was no significant difference in the rate of sinus rhythm maintenance at 3 years between the HD and non-HD groups (67.7% vs. 74.5%, respectively; log-rank P=0.62). CONCLUSIONS: ER in HD patients was a strong risk factor for LR. However, even HD patients could expect a good outcome without ER after the initial CA.

Reproducibility of cardiopulmonary exercise testing between one after and 1-3 weeks after elective percutaneous coronary intervention.

Prompt prescription and early initiation of exercise training are essential for patients undergoing elective percutaneous coronary intervention (PCI). We hypothesized that cardiopulmonary exercise testing (CPET) parameters determined the day after elective PCI during hospitalization would not differ from those obtained 1-3 weeks post-PCI in patients with stable coronary heart disease (CHD). CPET was performed the day after and 1-3 weeks (13±4.6; 7-21 days) after PCI. CPET was performed with a bicycle ergometer up to the ventilatory aerobic threshold (VAT) on the day after PCI. Symptom-limited CPET was conducted 1-3 weeks after PCI. No complications arose from the tests. There were no significant differences in %VAT (next day: 88.6±16.7 vs. 1-3 weeks later: 91.4%±18.7%), the workload at the VAT (51.8±11.0 W vs. 52.9± 11.6 W), heart rate (HR) at the VAT (95.3±105 beats/min vs. 94.1±11.3 beats/min), or metabolic equivalent (METs) at the VAT (3.69±0.69 vs. 3.84±0.78) between the two sessions. The slope of linear regression for two repeated measurements was close to 1 (%VAT, 1.02; workload at the VAT, 0.95; METs at the VAT, 1.03), except for HR (0.70). Bland-Altman plots revealed the reproducibility of all four CPET measurements between the two sessions. In conclusion, CPET up to the VAT can be performed safely 1-day post-PCI in patients with stable CHD. CPET parameters do not significantly differ between testing performed the day after and 1-3 weeks after PCI. Next-day CPET during hospitalization after PCI may enable prompt exercise prescription without the need for another CPET 1-3 weeks later.

Usefulness of three-dimensional pulmonary vein-left atrium image reconstructed from non-enhanced computed tomography for atrial fibrillation ablation.

Enhanced computed tomography (CT) is unsuitable for patients with reduced renal function and/or allergy for contrast medium (CM). CT image registration into an electroanatomic system (EAMS) is essential to perform pulmonary vein isolation (PVI) safely and smoothly in patients with atrial fibrillation (AF). To create three-dimensional pulmonary vein-left atrium (3D PV-LA) images from non-enhanced CT images to register them into EAMS for AF ablation. Using a non-enhanced ECG-gated image, 3D PV-LA images were generated by our developed techniques with an EnSite image analyzing tool for patients unfit for CM use (n = 100). Segmentation between tissues was performed as follows: tissues distal from or close to PV-LA were segmented in transverse slices to clearly show the whole LA. Tissues bordering PV-LA, including the pulmonary artery, left ventricle, and right atrium, were segmented manually with great care. Practical ablation parameters were compared with those obtained from enhanced CT (n = 100). 3D PV-LA image reconstruction from non-enhanced CT imaging required a longer time than that from enhanced CT (42 ± 6 vs 14 ± 3 min). All 100 PV-LA non-enhanced CT images were successfully reconstructed and registered into the EAM system without the need for re-segmentation. Practical ablation parameters, including procedural time and AF recurrence rate, did not differ between imaging methods. This study provides clinically useful information on a detailed methodology for 3D PV-LA image reconstruction using non-enhanced CT. Non-enhanced CT 3D PV-LA images were successfully registered into the EAM system and useful for patients unsuitable for CM use.

Small solitary atrial fractionated electrogram zone as a novel ablation target for persistent atrial fibrillation.

INTRODUCTION: Various adjunctive approaches to pulmonary vein isolation (PVI) have been attempted for persistent atrial fibrillation (perAF) and longstanding persistent AF (ls-perAF). We aimed to identify the novel zones responsible for perpetuation of AF. METHODS: To identify novel zones acting as a source of perAF and ls-perAF after PVI/re-PVI, we performed fractionation mapping in 258 consecutive patients with perAF (n = 207) and ls-perAF (n = 51) in whom PVI/re-PVI failed to restore sinus rhythm. RESULTS: In 15 patients with perAF (5.8%: 15/258), fractionation mapping identified a small solitary zone (<1 cm2 ) with high-frequency and irregular waves, showing fractionated electrograms (EGM). We defined this zone as the small solitary atrial fractionated EGM (SAFE) zone. The small SAFE zone was surrounded characteristically by a homogeneous area showing relatively organized activation with nonrapid and nonfractionated waves. Only one small SAFE zone was detected in each patient. This characteristic electrical phenomenon was observed stably during the procedure until ablation. AF duration, (defined as the duration between initial detection of AF and the current ablation) was longer in patients with the small SAFE zone than in those without (median, [25 and 75 percentiles]; 5.0 [3.5, 7.0] vs. 1.1 [1.0, 4.0] years, p = .0008). Longer AF cycle length was observed in patients with the small SAFE zone than in those without. The ablation of the small SAFE zone terminated AF in all 15 patients without any need for other ablations. AF/atrial tachycardia-free rate at follow-up was 93% (14/15) at 6 months, 87% (13/15) at 1 year, and 60% (9/15) at 2 years. CONCLUSIONS: Using fractionation mapping, this study identified a small SAFE zone surrounded characteristically by a homogeneous, relatively organized, low-excitability EGM lesion. The ablation of the small SAFE zone terminated AF in all patients, demonstrating it as a substrate for perpetuated AF. Our findings provide novel ablation targets in perAF patients with prolonged AF duration. Further studies to confirm the present results are warranted.

Optimal prevention method of phrenic nerve injury in superior vena cava isolation: efficacy of high-power, short-duration radiofrequency energy application on the risk points.

BACKGROUND OR PURPOSE: Superior vena cava isolation (SVCI) is widely performed adjunctively to atrial fibrillation (AF) ablation. Right phrenic nerve injury (PNI) is a complication of this procedure. The purpose of the study is to determine the optimal PNI prevention method in SVCI. METHODS: A total of 1656 patients who underwent SVCI between 2009 and 2022 were retrospectively examined. PNI was diagnosed based on the diaphragm position and movement in the upright position on chest radiographs before and after SVCI. RESULTS: With the introduction of various PN monitoring systems over the years, the incidence of SVCI-associated PNI has decreased. However, complete PNI avoidance has not been achieved. PNI incidence according to fluoroscopy-guided PN monitoring, high-output pace-guided, compound motor action potential-guided, and 3-dimensional electro-anatomical mapping (EAM) systems was 8.1% (38/467), 2.7% (13/476), 2.4% (4/130), and 2.8% (11/389), respectively. However, a high-power, short-duration (50 W/7 s) radiofrequency (RF) energy application only on PNI risk points tagged by a 3-dimensional EAM system completely avoids PNI (0%; 0 /160 since April 2021). PNI showed no symptoms and recovered within an average of 188 days post-SVCI, except for a few patients who required > 1 year. CONCLUSIONS: Although PNI incidence decreased annually with the introduction of various monitoring systems, these monitoring systems did not prevent PNI completely. Most notably, the delivery of a high-power, short-duration RF energy only on risk points tagged by EAM prevented PNI completely. PNI recovered in all patients. The application of higher-power, shorter-duration RF energy on risk points tagged by EAM appears to be an optimal PNI prevention maneuver.

Atrial Fibrillation Ablation Outcomes and Heart Failure (from the Kansai Plus Atrial Fibrillation Registry).

The impact of rhythm outcomes on heart failure (HF) hospitalizations remains unknown after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We sought to elucidate whether AF recurrence was associated with HF hospitalizations after AF RFCA. We conducted a large-scale, prospective, multicenter, observational study (Kansai Plus Atrial Fibrillation Registry), enrolling 5,010 consecutive patients (age 64 ± 10 years, 27.3% female, and 35.7% nonparoxysmal AF) who underwent an initial AF RFCA at 26 centers. The median follow-up duration was 2.9 years. The cumulative 3-year incidence of HF hospitalizations after the initial RFCA was 1.84% (0.69%/year). Hospitalized patients with HF were older with a higher prevalence of nonparoxysmal AF, renal dysfunction, diabetes, and underlying heart disease pre-RFCA. HF hospitalizations occurred more often in patients with than without recurrences (3.27 vs 0.84%, log-rank p <0.0001). After adjusting for confounders using a Cox model, AF recurrence remained an independent predictor of HF hospitalizations (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.80 to 4.47, p <0.0001). AF recurrence was a distinct HF hospitalization risk in patients with a left ventricular ejection fraction ≥50% (HR 4.54, 95% CI 2.38 to 8.65, p <0.0001) but not <50% (HR 1.31, 95% CI 0.65 to 2.62, p = 0.45), with significant interactions. Furthermore, patients with AF recurrences within 1 year had a greater HF hospitalization risk after 1 year (1.61% vs 0.79%, log-rank p = 0.019). In conclusion, AF recurrence after RFCA was independently associated with HF hospitalizations.

Catheter Ablation for Paroxysmal Atrial Fibrillation With Sick Sinus Syndrome: Insights From the Kansai Plus Atrial Fibrillation Registry.

BACKGROUND: Coexisting sick sinus syndrome (SSS) is associated with both electrical and structural atrial remodelling in patients with atrial fibrillation (AF). Limited data are available concerning catheter ablation (CA) for AF in this condition. This study investigated the efficacy of CA as a curative therapy for AF and SSS in a large-scale prospective multicentre registry. METHODS: The Kansai Plus Atrial Fibrillation (KPAF) registry enrolled 5,010 consecutive patients who underwent CA for AF; this included 3,133 patients with paroxysmal AF (mean age, 66 years; male, 69.3%; mean CHA2DS2-VASc score, 2.05±1.50; SSS, n=315 [tachy-brady syndrome, n=285]). The endpoints included the recurrence of AF with a blanking period of 90 days after CA, and de novo pacemaker implantation during the follow-up period (median duration, 2.93 years). RESULTS: The AF-free survival did not significantly differ between patients with and those without SSS (n=2,818) after the initial (log-rank p=0.864) and final sessions (log-rank p=0.268). Pacemakers were implanted in 48 patients with SSS, and implantation in this group was significantly associated with AF recurrence, including early recurrence (adjusted odds ratio, 3.57; 95% confidence interval, 1.67-7.64; p=0.002). The remaining 85.3% of patients with SSS did not require pacemaker implantation at 3 years after CA. CONCLUSIONS: Coexisting SSS did not adversely affect recurrence-free survival after CA for paroxysmal AF. Pacemaker implantation was not required in most patients with SSS, with AF recurrence serving as a strong predictor for this.

Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study.

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1ß-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1ß-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints.

Rates of atrial flutter occurrence and cavotricuspid isthmus reconduction after prophylactic isthmus ablation performed during atrial fibrillation ablation: a clinical study, review, and comparison with previous findings.

PURPOSE: Based on the high rate of coexisting atrial fibrillation (AF) and atrial flutter (AFL), prophylactic cavotricuspid isthmus ablation (CTIA) adjunctive to AF ablation has recently been attempted in patients with AF and without AFL. The present study aimed to determine the rates of AFL occurrence and CTI reconduction after performing CTI ablation adjunctive to AF ablation. METHODS: We analyzed the data of 3833 consecutive patients with AF, who underwent prophylactic CTIA with AF ablation between 2009 and 2020. RESULTS: In all patients, CTIA and AF ablations were successful. Clinical AFL occurred in seven patients (0.18%, 7/3,833), and the observed rate was lower than those reported for cases of AF ablation without CTIA and for those of CTIA for pure AFL. A second ablation was needed in 745 patients at a median of 253 days (25 and 75 percentiles, 116 and 775 days) after the first ablation. In 12.1% (90/745) of the patients, CTI reconduction was observed. The reconduction rate was lower than that previously reported for CTIA for pure AFL. CONCLUSIONS: The present retrospective study found acceptably low rates of clinical AFL occurrence and CTI reconduction following prophylactic CTIA performed with AF ablation, which was supported by the findings obtained after performing a comparison of the rates with those of other ablations (AF ablation only and CTIA for pure AFL). Considering the high correlation between AF and AFL, the present study provided information regarding the efficacy of adjunctive CTIA.

Long-term prognosis of patients undergoing radiofrequency catheter ablation for atrial fibrillation: comparison between heart failure subtypes based on left ventricular ejection fraction.

AIMS: Heart failure (HF) prognosis has been reported similar in patients with preserved vs. reduced left ventricular ejection fraction (LVEF). This study compared the long-term prognosis of HF patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). METHODS AND RESULTS: Among 5010 patients undergoing RFCA in Kansai Plus AF registry, 656 patients (13.1%) with a documented history of HF were enrolled in the study before RFCA. The primary endpoint was a composite of all-cause death, HF hospitalization, and stroke or systemic embolism. Patients with reduced (<40%), mid-range (40-49%), and preserved (≥50%) LVEF were 98 (14.9%), 107 (16.3%), and 451 (68.8%) patients, respectively. The prevalence of ischaemic heart disease and cardiomyopathies was higher among patients with reduced as compared with preserved LVEF (27.6% vs. 10.0%, P < 0.05 and 36.7% vs. 15.3%, P < 0.05, respectively). The median follow-up period was 2.9 years. The 3-year cumulative risk for the primary endpoint was higher in patients with reduced LVEF (32.7%) compared to those with mid-range (11.7%) or preserved (11.6%) LVEF (P < 0.001). Reduced LVEF was the most significant independent risk factor for primary endpoint (hazard ratio, 2.83; 95% confidence interval 1.74-4.61, P < 0.001). The 3-year arrhythmia recurrence rate was similar among the groups (48.2%, 42.8%, and 47.3%, respectively, P = 0.75). CONCLUSION: This study raises hypothesis that patients with HFrEF and AF had approximately three times higher risk for a composite of all-cause death, HF hospitalization, and stroke or systemic embolism after AF ablation compared with patients with HFmrEF or HFpEF.

Real-World Safety Profile of Atrial Fibrillation Ablation Using a Second-Generation Cryoballoon in Japan: Insight From a Large Multicenter Observational Study.

OBJECTIVES: This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan. BACKGROUND: Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy. METHODS: This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected. RESULTS: Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia. CONCLUSIONS: This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.

Long-term efficacy and safety of anticoagulation after atrial fibrillation ablation: data from the JACRE registry.

BACKGROUND: Catheter ablation (CA) is an important strategy for managing atrial fibrillation (AF). However, long-term anticoagulation strategies and clinical outcomes following CA, including thromboembolism and bleeding, have not yet been elucidated. METHODS: We established a prospective registry, called the JACRE registry, for patients on rivaroxaban or warfarin administration who received CA for AF. The outcomes up to 30 days following the procedure were reported previously. The present study involved longer follow-up of patients enrolled in this registry to evaluate long-term anticoagulation strategies and clinical outcomes. RESULTS: Data of 975 patients (rivaroxaban, n = 823; warfarin, n = 152) were collected from 27 institutes. Patient population had mean age 63.7 ± 10.3 years, 710 (72.8%) males, mean CHA2DS2-VASc score 1.9 ± 1.5, and mean follow-up period 28.7 ± 12.7 months after the index procedure. Anticoagulants were continued in 496 (50.9%) patients during the follow-up. Thromboembolism occurred in 3 patients, hemorrhagic stroke in 5, and major bleeding events in 9 (annualized event rate, 0.13%, 0.22%, and 0.40% per patient-year, respectively). There were no differences in the composite event rate of thromboembolism and International Society on Thrombosis and Haemostasis major bleeding between rivaroxaban and warfarin cohorts (0.53% and 0.55% per patient-year, respectively). CONCLUSIONS: Long-term incidence of thromboembolism was extremely low in patients with AF treated with CA, while that of major bleeding was not especially low. Clinical Trials Registry: UMIN000032829 / UMIN000032830.

Efficacy of an Adjunctive Electrophysiological Test-Guided Left Atrial Posterior Wall Isolation in Persistent Atrial Fibrillation Without a Left Atrial Low-Voltage Area.

BACKGROUND: Electrical remodeling precedes structural remodeling. In adjunctive left atrial (LA) low-voltage area (LVA) ablation to pulmonary vein isolation of atrial fibrillation (AF), LA areas without LVA have not been targeted for ablation. We studied the effect of adjunctive LA posterior wall isolation (PWI) on persistent AF without LA-LVA according to electrophysiological testing (EP test). METHODS: We examined consecutive patients with persistent AF with (n=33) and without (n=111) LA-LVA. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54) groups. In the EP test-guided group, an adjunctive PWI was performed in those with positive results (PWI subgroup; n=24), but not in those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, effective refractory period>20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia (AT) during measurements. LVA ablation was performed in the patients with LA-LVA. RESULTS: During the follow-up period (62±33 weeks), the EP test-guided group had significantly lower recurrence rates (19%,11/57 versus 41%, 22/54, P=0.012) and higher Kaplan-Meier AF/AT-free survival curve rates than the control group (P=0.01). No significant differences in the recurrence and AF/AT-free survival curve rates between the PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analyses identified EP test-guided ablation as a factor reducing the recurrence rate. The recurrence rates in the LA-LVA ablation group and EP test-guided group were similar. CONCLUSIONS: This pilot study proposed that an EP test-guided adjunctive PWI of persistent AF without LA-LVA potentially reduced AF/AT recurrences. The results suggest that there is an AF substrate in the LA with altered electrophysiological function even when there is no LA-LVA. Graphic Abstract: A graphic abstract is available for this article.

Correlation of the peak oxygen consumption and ventilatory aerobic threshold by cardiopulmonary exercise testing with atrial fibrillation recurrences after ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The cardiopulmonary function is hypothesized to be associated with atrial fibrillation/atrial tachyarrhythmia (AF/AT) recurrence after AF ablation. PURPOSE: To clarify the relationship between the cardiopulmonary function after successful ablation and AF/AT recurrence. METHODS: We examined 31 patients with paroxysmal AF who underwent AF ablation. Cardiopulmonary exercise testing (CPET) was performed at 1month after the ablation. A continuously increasing loading method on a bicycle ergometer was employed for the CPET. RESULTS: No adverse events, including AF/AT recurrence, occurred during the CPET. Among 31 patients, AT/AF recurrence was observed in seven (23%). The ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO2) were significantly higher in patients without AF/AT recurrence than in those with AT/AF recurrences (peak VO2 23.6 ± 5.7 vs 17.2 ± 4.1 mL/kg/min; VAT, 16.7 ± 2.8 vs 13.8 ± 2.7 mL/min/kg). The areas under the receiver operating characteristic curve for the peak VO2 and VAT were 0.786 (P < .01) and 0.789(P < .01), respectively. Both indices had a sensitivity of 70%-80% and specificity of 70%-80% for predicting AT/AF recurrence. Similar results were obtained for the percent values of the predicted peak VO2 and VAT. CONCLUSIONS: The present pilot study found that CPET can be performed safely at approximately 1 month after AF ablation. The peak VO2 and VAT were significantly associated with AT/AF recurrence. The peak VO2 and VAT were thought to provide helpful information regarding AT/AF recurrence.

Sex differences in atrial fibrillation ablation outcomes: insights from a large-scale multicentre registry.

AIM: The impact of sex differences on the clinical outcomes of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is controversial. We investigated the sex differences regarding the efficacy and clinical outcomes of RFCA of AF. METHODS AND RESULTS: We conducted a large-scale, prospective, multicentre, observational study (Kansai Plus Atrial Fibrillation Registry). We enrolled 5010 consecutive patients who underwent an initial RFCA of AF at 26 centres (64 ± 10 years; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Female patients (n = 1369, 27.3%) were older (female vs. male, 68 ± 9 vs. 63 ± 11 years, P < 0.0001) with a lower prevalence of non-paroxysmal AF (27.1% vs. 38.9%, P < 0.0001). Fewer females experienced time-dependent pulmonary vein (PV) reconnections and more females received a non-PV foci ablation than males in the index RFCA. The 3-year cumulative incidence of AF recurrences in the multivariate analysis after single procedures was significantly higher in females than males (43.3% vs. 39.0%, log rank P = 0.0046). Females remained an independent predictor of AF recurrence (hazard ratio 1.24; 95% confidence interval 1.12-1.38, P < 0.0001). The AF recurrence rates after multiple procedures were also higher in females, but fewer females experienced PV reconnections during second sessions. More females experienced de novo pacemaker implantations during the long-term follow-up. Females were associated with a higher risk of heart failure hospitalizations and major bleeding after RFCA in the multivariate analysis. CONCLUSIONS: Females experienced more frequent AF recurrences probably due to non-PV arrhythmogenicity and de novo pacemaker implantations than males during the long-term follow-up after RFCA of AF.

Activated clotting time on the day of atrial fibrillation ablation for minimally interrupted and uninterrupted direct oral anticoagulation therapy: Sequential changes, differences among direct oral anticoagulants, and ablation safety outcomes.

BACKGROUND: Activated clotting time (ACT)-guided heparinization is used during atrial fibrillation (AF) ablation. Differences in sensitivity to ACT assays have been identified among different direct oral anticoagulants (DOACs). OBJECTIVE: We aimed to examine ACT just before ablation (pre-ACT) for different ablation start times (9:00, 11:00, 13:00, or 15:00) and ablation safety outcomes in minimally interrupted (min-Int) and uninterrupted (Unint) DOAC regimens and examine differences in pre-ACT values among four DOACs. METHODS: Consecutive patients were randomized into the min-Int (n = 307) or Unint (n = 277) groups. DOACs examined were apixaban, dabigatran, edoxaban, and rivaroxaban. RESULTS: No sequential changes in pre-ACT values were observed for each DOAC used and for all four DOACs combined in the min-Int and Unint groups. There was no meaningful difference in pre-ACT at each ablation start time between the groups. Clinically significant differences in overall pre-ACT were not obtained between the groups (138 ± 24 vs 142 ± 23 seconds). The pre-ACT (baseline) value for dabigatran was on average 29 seconds higher than that for the other three DOACs. The min-Int and Unint groups showed similar thromboembolic (0% vs 0%) and bleeding event rates (major, 1% vs 0%; all, 3.5% vs 2.5%). CONCLUSION: The pre-ACT did not show a sequential change in the min-Int and Unint groups. No notable differences in the time-dependent change in pre-ACT between the groups were observed. Variations in baseline ACT suggest the need for moderate adjustment of ACT for adequate modification of heparin dose for the other three DOACs. Both regimens provided similar acceptable AF ablation safety outcomes.

Effects of Oral Anticoagulants on Patients With Atrial Fibrillation Aged 90 Years and Older: Comparison Among Direct Oral Anticoagulant, Warfarin Anticoagulant, and Nonanticoagulation.

This study aimed to investigate the effects of anticoagulants on ultra-aged patients with nonvalvular atrial fibrillation (AF). We retrospectively studied 320 consecutive patients with AF (median age, 91 years; range 90-100.1 years). Patients were categorized as follows: patients taking direct oral anticoagulant (DOAC group, n = 93), those taking warfarin (warfarin group, n = 147), and those not taking oral anticoagulants (non-OAC group, n = 80). During the follow-up periods (median 3.00 years; first and fourth quantiles, 1.13 and 4.56 years, respectively), in thromboembolic events, the DOAC, warfarin, and non-OAC groups showed the lowest (0%, 0/93; 0%/year), intermediate (4.7%, 7/149; 1.43%/year), and highest (5%, 4/80; 2.65%/year) incidence rates, respectively. In major bleeding events, the DOAC, warfarin, and non-OAC groups showed the highest (9.67%, 9/96; 5.00%/year), intermediate (8.1%, 12/149; 2.46%/year), and lowest (0%, 0/80; 0%/year) incidence rates, respectively. These differences in the relationships of the 3 groups were statistically significant. Confounding factors did not affect these results. Bruises associated with impairment of motor function with aging caused major bleeding in approximately 60% of major bleeding cases. The Cox proportional hazards model revealed that warfarin decreased mortality, whereas antiplatelet drugs increased mortality. In conclusion, DOACs had considerably high incidence of major bleeding events, whereas absence of OAC treatment was associated with substantially high thromboembolic events. Warfarin showed acceptable incidence ratios of both events. At present, warfarin is thus believed to be adequate for ultra-aged (≥90 years) patients with nonvalvular AF. Avoidance of bruises was important to prevent major bleeding events. Antiplatelet drugs were suggested not to be adequate for these patients.