Variation in the frozen lesion size according to the non-occluded application duration and technique for cryoballoon ablation.

OBJECTIVE: The frozen lesion formation created by cryoballoon ablation, especially with non-occluded applications, has not been fully evaluated. This study aimed to validate the lesion size under different cryoballoon ablation settings: application duration, push-up technique, and laminar flow. METHODS: The frozen lesion size was evaluated immediately after ending the freezing with three different application durations (120, 150, and 180 seconds) in porcine hearts (N = 24). During the application, the push-up technique was applied at 10, 20, and 30 seconds after starting the freezing with or without laminar flow. RESULTS: The lesion size was significantly correlated with the nadir balloon temperature (P<0.001). The lesion volume became significantly larger after 150 seconds than 120 seconds (1272mm3 versus 1709mm3, P = 0.004), but not after 150 seconds (versus 1876mm3 at 180 seconds, P = 0.29) with a comparable nadir balloon temperature. Furthermore, the lesion volume became significantly larger with the push-up technique with the largest lesion size with a 20-second push-up after the freezing (1193mm3 without the push-up technique versus 1585mm3 with a push-up at 10 seconds versus 1808mm3 with a push-up at 20 seconds versus 1714mm3 with a push-up at 30 seconds, P = 0.04). Further, the absence of laminar flow was not associated with larger lesion size despite a significantly lower nadir balloon temperature. CONCLUSION: The frozen lesion size created by cryoballoon ablation became larger with longer applications at least 150 seconds and with a push-up technique especially at 20 seconds after the freezing.

Reliable focal and rotational activations in CARTOFINDER mapping using the OctaRay catheter.

INTRODUCTION: The aim of the current study was to elucidated the reliable atrial fibrillation (AF) drivers identified by CARTOFINDER using OctaRay catheter. METHODS AND RESULTS: The reliability of focal and rotational activations identified by CARTOFINDER using OctaRay catheter was assessed by the sequential recordings in each site of both atrium before and after pulmonary vein isolation (PVI) in 10 persistent AF patients. The outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI as reliable focal and rotational activations. The study results were compared with those under use of PentaRay catheter (N = 18). Total 68928 points of 360 sites in OctaRay group and 24 177 points of 311 sites in PentaRay were assessed. More focal activation sites were identified in OctaRay group than PentaRay group (7.9% vs. 5.7%, p < .001), although the reproducibility rate and the stability rate were significantly lower in OctaRay group (45.3% vs. 58.9%, p < .001; 11.2% vs. 28.4%, p < .001). Meanwhile, the prevalence of reproducible focal activation sites among overall points was comparable (3.6% vs. 3.3%, p = .08). Regarding rotational activation, more rotational activation sites were identified in OctaRay group (5.1% vs. 0.2%, p < .001), and the reproducibility rate and the stability rate were significantly higher in OctaRay group (45.2% and 12.5% vs. 0.0%, p < .001). Both reliable focal and rotational activation sites were characterized by significantly shorter AF-cycle length (CL) and higher repetition of focal and rotational activations during the recordings compared with the sites of non or unreliable focal and rotational activations. CONCLUSION: In CARTOFINDER, OctaRay catheter could identify reliable focal activation with high resolution and reliable rotational activation compared with PentaRay catheter. The repetitive focal and rotational activations with short AF-CL could be the potential target during ablation.

Intracardiac energy inefficiency during atrial fibrillation rhythm with heart failure: Assessment by echo-vector flow mapping.

AIMS: Intracardiac dynamics during atrial fibrillation(AF) complicated by heart failure(HF) are not fully understood. The aim of this study was to evaluate the impact of intracardiac dynamics assessed by echo-vector flow mapping on AF complicated by HF. METHODS AND RESULTS: We enrolled 76 AF patients receiving sinus restoration therapy and assessed energy loss(EL) by echo-vector flow mapping during both AF rhythm and sinus rhythm. Patients were divided into 2 groups according to serum NT-proBNP level: high NT-proBNP group(≥1800 pg/ml during AF rhythm: N = 19), and low NT-proBNP group(N = 57). Outcome measures were average ELs/stroke volume(SV) in left ventricle(LV) and left atrium(LA). Average EL/SVs during AF rhythm in the LV and LA were significantly larger in the high NT-proBNP group than the low NT-proBNP group(54.2 mE/m·L versus 41.2 mE/m·L, P = 0.02; 3.2 mE/m·L versus 1.9 mE/m·L, P = 0.01). The significantly larger EL/SV in the high NT-proBNP group was recorded for maximum EL/SVs. In patients with high NT-proBNP, large vortex formation with extreme EL was detected in the LV and LA during the diastolic phase. After sinus restoration, the average decrease of EL/SV in the LV and LA was larger in the high NT-proBNP group(-21.4 mE/m·L versus +2.6 mE/m·L, P = 0.04; -1.6 mE/m·L versus -0.3 mE/m·L, P = 0.02). Average EL/SV during sinus rhythm did not significantly differ between the high and low NT-proBNP groups in the LV and LA. CONCLUSIONS: High EL during AF rhythm as intracardiac energy inefficiency was associated with high serum NT-proBNP levels and improved after sinus restoration.

Reproducibility and stability of atrial fibrillation drivers identified by an automated algorithm: CARTOFINDER.

BACKGROUND: The characteristics of atrial fibrillation (AF) drivers identified by CARTOFINDER have not been thoroughly evaluated. Therefore, the current study was sought to validate the reliability of AF drivers. METHODS: The reliability of focal and rotational activation identified by CARTOFINDER during AF was assessed by the sequential recordings in each site before and after pulmonary vein isolation (PVI) in 27 persistent AF patients. The primary outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI. RESULTS: Among 32,135 points in 509 sites, focal activation was identified in 1775 points (5.5%) with a repetition of 11 (6-26) times during the recording. Rotational activation was identified in 132 points (0.4%) with a repetition number of 21 (14-21) times. AF drivers had significantly higher voltage and shorter AF cycle length than non-AF driver sites. The reproducibility rate of focal activation during the sequential recordings was 57.8% and increased with the repetition number. The reproducibility rate of rotational activation was 37.4%. The prevalence and the reproducibility rate of focal activation in post-PVI were significantly lower than pre-PVI (5.3% versus 6.0%, P = 0.02; 53.4% versus 63.6%, P < 0.001). The stability rate of focal activation between pre- and post-PVI was only 28.3% but increased with the repetition number. There was no stable rotational activation between pre- and post-PVI. CONCLUSIONS: The reproducibility of AF drivers, especially focal activation, identified by CARTOFINDER is relatively favorable, but the stability between pre- and post-PVI was poor. These results depended on the repetition number during the recording.

Instability of rotational activation as atrial fibrillation drivers: Assessment by ExTRa Mapping system.

BACKGROUND: ExTRa Mapping™ has developed to visualize rotational activation as atrial fibrillation (AF) drivers. The current study was sought to evaluate the instability of AF drivers by ExTRa Mapping™. METHODS: Variation of nonpassively activated ratio (%NP) among three-time repetitive recordings before and after pulmonary vein isolation (PVI) in left atrium was assessed in 26 persistent AF patients. The recoding time was set at 5 or 8 s for the respective patients. The outcome measures included %NP at each recording, mean value of the three-time recordings, and the instability index, which was defined as maximum difference per mean %NP × 100 (%). RESULTS: Total 683 sites 2049 recordings were assessed. Mean %NP was 33.3(23.3-42.7)%, and higher in sites with severe (≥50%) and patchy low voltage area than those without, but not in those with severe complex fractionated atrial electrogram area. There was significant correlation between actual and mean %NP (R = 0.86, P < .001), but maximum difference among the repetitive recordings was 16(10-24)%. The instability index of %NP was 55.9(30.9-83.6)%, and significantly lower at the recordings of 8 s compared with 5 s (50.6[28.6-78.4]% vs. 60.4[35.0-90.0]%, P = .004). Furthermore, it was higher at sites with lower reliability of the recordings. After PVI, mean %NP significantly decreased (28.7[18.3-36.7]% vs. 37.7[28.7-45.7]%, P < .001), but the instability index significantly increased compared with those before PVI (60.0[35.0-92.7]% vs. 48.9[29.1-75.0]%, P = .001). CONCLUSION: Rotational activation as AF drivers assessed by ExTRa Mapping™ is unstable, and repetitive and longer recording is required for the reliable assessment even after PVI.

Different Kinetics of Activated Clotting Time Among Uninterrupted Oral Anticoagulants During Catheter Ablation Procedure.

Activated clotting time (ACT) kinetics under uninterrupted oral anticoagulants (OACs) has not been fully evaluated. The present study is sought to validate ACT kinetics including stability under uninterrupted use of OACs during an ablation procedure in daily clinical practice. We prospectively enrolled consecutive 554 patients with atrial fibrillation who underwent catheter ablation procedure under uninterrupted OACs. We evaluated ACT kinetics at an interval of 15 minutes during the procedure and periprocedural complications among 5 OACs (dabigatran [N = 46], rivaroxaban [N = 125], apixaban [N = 129], edoxaban [N = 184], and warfarin [N = 70]). Compared with the dabigatran group, time to achieve target ACT was significantly longer in the rivaroxaban and apixaban groups, but not in the edoxaban and warfarin groups (8.7 vs 11.7 minutes, P < .001; 13.3 minutes, P < .001; 8.8 minutes, P = .64; 10.3 minutes, P = .19, respectively). Heparin dose to achieve target ACT was comparable except for the warfarin group, whereas, compared with the dabigatran group, time in therapeutic range of ACT within the first hour was comparable in the rivaroxaban and apixaban group but significantly lower in the edoxaban and warfarin groups (73.7 % vs 63.0%, P = .06; 67.0 %, P = .16; 59.2 %, P = .001; 58.2%, P = .004, respectively). In multiple regression analysis, low body weight, rivaroxaban, apixaban, and morning session had significant associations with time and heparin dose to achieve target ACT, and there were positive associations of dabigatran and apixaban with time in therapeutic range of ACT within the first hour. The incidence of periprocedural complications did not significantly differ among the 5 groups. Under uninterrupted OAC use in daily clinical practice, dabigatran showed faster achievement of target ACT and higher stability of ACT than other OACs.

Association between serum inflammatory biomarkers and atrial low voltage in patients with atrial fibrillation: A phase 1 FIB-MARK study.

BACKGROUND: The mechanisms leading to atrial fibrosis in patients with atrial fibrillation (AF), especially in relation to inflammation, remain unclear. METHODS AND RESULTS: Forty biomarkers were measured in peripheral blood samples collected prior to catheter ablation, and the association with left atrial (LVZ) was evaluated in 16 consecutive patients. The median %LVZ was 17%. In Pearson's correlation analysis, interleukin(IL)-17A and interferon(IFN)-γ showed the most significant positive and negative correlations with %LVZ (R = 0.35 and 0.43, P < 0.001). Furthermore, the IL-17A/IFN-γ ratio was significantly associated with %LVZ (R = 0.65, P = 0.007), as was the macrophage inflammatory protein (MIP)-1δ/IFN-γ ratio (R = 0.73, P = 0.001). The area under the receiver operator characteristics curves of the IL-17A/IFN-γ and MIP-1δ/IFN-γ ratios for detecting severe LVZ (%LVZ ≥ 10% as a reference standard) were 0.88 and 0.90, respectively. The IL-17A/IFN-γ ratio was significantly higher in patients with severe LVZ than those without (1.41 versus 0.97, P = 0.01). Furthermore, the sensitivity, specificity, and accuracy for detecting severe LVZ were 60%, 100%, and 75.0%, respectively, at a cut-off value of 1.3. CONCLUSIONS: Among inflammatory biomarkers, the serum IL-17A/IFN-γ ratio was associated with severe left atrial LVZ in patients with AF. However, further studies are needed to clarify the role of inflammatory biomarkers in the development and progression of atrial fibrosis in patients with AF.

The impact of current strategy using intracardiac echocardiography, lesion index, and minimum substrate ablation on clinical outcomes after catheter ablation procedure for atrial fibrillation.

PURPOSE: We developed the intracardiac echocardiography (ICE) technique to minimize radiation exposure and other recent technology during ablation procedure for atrial fibrillation (AF). The aim of this study was to validate the impact of the current strategy using the recent technology for AF ablation on outcomes after procedure. METHODS: We evaluated the safety and efficacy of the current strategy in consecutive set of patients undergoing first-time ablation for AF (N = 233) compared with the conventional strategy in earlier consecutive set of patients (N = 223). The current strategy included the technique of ICE to reduce radiation exposure, Ablation Index®-guided pulmonary veins isolation, and minimum substrate ablation targeting only for induced AF. Outcome measures were radiation exposure, procedure time, in-hospital adverse outcomes, and event-free survival from tachyarrhythmias. RESULTS: Puncture-to-ablation time was slightly, but significantly increased in the current strategy than in the conventional strategy (48.0 minutes vs 44.7 minutes, P = .002), although total procedure time was significantly decreased in the current strategy (143.9 minutes vs 156.9 minutes, P < .001). Likewise, radiation time and absorbed dose were significantly decreased in the current strategy (9.8 minutes vs 38.8 minutes, P < .001; 102.3 mGy vs 490.5 mGy, P < .001). The incidence of overall in-hospital adverse outcomes was 3.9% in the current strategy and each complication rate was comparable with the conventional protocol. The event-free survival from recurrent atrial tachyarrhythmias was not significantly different between two groups (72.3% vs 77.1% at 2-year, P = .32). CONCLUSION: The current strategy using the recent technology with ICE, lesion index, and minimum substrate ablation was feasible and reduced total procedure time and radiation exposure. However, the arrhythmia-free survival could not be improved.

Influence of low body weight on long-term clinical outcomes in patients with venous thromboembolism: From the COMMAND VTE registry.

INTRODUCTION: There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE). MATERIALS AND METHODS: The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (>60 kg). RESULTS: Patients with lower body weight were older (70.8 versus 60.9 years, P < 0.001), and more often women (75% versus 38%, P < 0.001), and more often had active cancer (27% versus 19%, P < 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P < 0.001, and 35.8% versus 19.8%, P < 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P < 0.001, respectively). CONCLUSIONS: In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.

Optimal cutoff value of bipolar low-voltage in electroanatomic voltage mapping during atrial fibrillation rhythm.

BACKGROUND: Electroanatomic voltage mapping (EAVM) of the left atrium (LA) with multielectrodes is usually acquired during sinus rhythm (SR), and the feasibility of EAVM during atrial fibrillation (AF) rhythm is unclear. METHODS: We performed EAVM of LA during both SR and AF rhythm in 44 patients undergoing catheter ablation for AF and validated the optimal cutoff value of low-voltage area (LVA) during AF rhythm for detecting LVA defined as bipolar voltages ≤0.5 mV during SR. RESULTS: In each session, mean 829 and 552 points were acquired by multielectrodes during SR and AF rhythm, respectively. Mean proportion of LVA was 4.9% among LA surface area of 276.2 cm2 . Differences of LVA proportions between SR and AF rhythm were 5.8% (P < 0.001), 4.2% (P < 0.001), 2.7% (P < 0.001), 1.2% (P = 0.01), and -0.5% (P = 0.17) at the cutoff value of 0.4, 0.35, 0.3, 0.25, and 0.2 mV during AF rhythm, respectively. There was a good correlation between LVA proportions during SR and AF rhythm with cutoff value of 0.2 mV (R = 0.88, P < 0.001) and 37 patients (84.1%) had the discrepancy of LVA proportions within 3%. Furthermore, there was no significant difference between LVA proportions at each segment of LA. The discrepancy was relatively large in patients with large LA dimension and LVA during SR. CONCLUSION: EAVM during AF rhythm was feasible and the optimal cutoff value of LVA was 0.2 mV for detecting LVA ≤ 0.5 mV during SR. However, the evidence is restricted to patients with relatively small LVA.

Limitations of lesion quality estimated by ablation index: An in vitro study.

LIMITATIONS OF THE ABLATION INDEX BACKGROUND: Ablation index (AI) is a novel marker of lesion quality from radiofrequency (RF) catheter ablation. However, AI reliability has not been fully validated by experimental data. The aim of the present study is to validate AI reliability for estimating lesion size using different settings for RF parameters: contact angle, power delivery, and contact force (CF). METHODS AND RESULTS: We evaluated the lesion size in porcine hearts (N = 108) after RF application at three different contact angles to the myocardium: perpendicular (90°), oblique (45°), and parallel (0°). At each angle, RF power at 25, 30, and 35 W was applied at target CF values of 5, 15, and 30 g as measured by the CF sensor to reach target AIs of 300, 400, 500, and 600. AI value was significantly correlated with lesion depth, width, and volume (R = 0.84, 0.82, and 0.87, respectively, all P < 0.001). Lesion depth decreased with smaller contact angles (45° and 0°). Furthermore, high-power RF energy (35 W) resulted in a significantly smaller lesion volume compared with standard-power energy (30 W). There were no significant differences in lesion size among CF settings. CONCLUSIONS: AI was strongly correlated with lesion depth, width, and volume, but only within a small range of contact angles and RF power delivery settings.