Extensive ablation for persistent atrial fibrillation patients with mitral regurgitation: Insights from the EARNEST-PVI prospective randomized trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients. METHODS: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications. RESULTS: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54-1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22-0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms. CONCLUSIONS: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management.

Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

BACKGROUND: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers.Methods and Results: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). CONCLUSIONS: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Tip Detection-Antegrade Dissection and Re-Entry With New Puncture Wire in CTO Intervention: Revolution Through 3D-Wiring.

Background: The authors devised the tip detection (TD) method and developed AnteOwl WR intravascular ultrasound to standardize intravascular ultrasound-based 3-dimensional wiring for intraplaque tracking in chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). The TD method also allowed antegrade dissection and re-entry (ADR). Combining TD-ADR with Conquest Pro 12 Sharpened Tip (CP12ST) wire, a new ADR wire with the strongest penetration force developed to date, enabled re-entry anywhere except calcification sites. Objectives: This study investigated the efficacy and feasibility of TD-ADR by comparison of procedural outcomes with Stingray-ADR in CTO-PCI. Methods: Twenty-seven consecutive CTO cases treated by TD-ADR with CP12ST wire between August 2021 and April 2023 and 27 consecutive CTO cases treated by Stingray-ADR with Conquest 8-20 (CP20) wire between March 2018 and July 2021 were retrospectively enrolled as the TD-ADR by CP12ST wire group and Stingray-ADR by CP20 wire group, respectively, from 4 facilities that could share technical information on these procedures. Results: The success rate of the ADR procedure was significantly improved (27 of 27 cases [100%] vs 18 of 27 cases [67%], respectively; P = 0.002) and total procedural time was significantly reduced (median procedural time: 145.0 [Q1-Q3: 118.0-240.0] minutes vs 185.0 [Q1-Q3: 159.5-248.0] minutes, respectively; P = 0.028) in the TD-ADR by CP12ST wire group compared to the Stingray-ADR by CP20 wire group. There were few in-hospital major adverse cardiac and cerebrovascular events or no complications in either group. Conclusions: TD-ADR by CP12ST wire can standardize highly accurate ADR in CTO-PCI.

Duration of atrial fibrillation persistence: Implications for recurrence risk after catheter ablation and efficacy of additional substrate ablation.

BACKGROUND: The optimal duration of atrial fibrillation (AF) persistence for predicting poor outcomes after catheter ablation of long-standing AF (LsAF) and the best ablation strategy for these patients remain unclear. OBJECTIVE: We aimed to assess the impact of the duration of AF persistence on outcomes after catheter ablation of AF. METHODS: We analyzed the Efficacy of Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation (EARNEST-PVI) trial data comparing pulmonary vein isolation (PVI) alone (PVI-alone) with additional linear ablation or defragmentation (PVI-plus) in persistent AF (PerAF). Patients who received catheter ablation by contact force-sensing catheter were enrolled in the study. In patients with LsAF, the optimal cutoff duration of AF persistence was evaluated. With use of the threshold, patients with LsAF were divided into 2 groups and compared with PerAF <1 year for arrhythmia-free survival after a 3-month blanking period. RESULTS: The optimal cutoff duration was 2.4 years. Of 458 patients, arrhythmia-free survival rates for LsAF 1-2.4 years were comparable to those of PerAF (hazard ratio [HR], 1.01; 95% CI, 0.67-1.52). However, LsAF >2.4 years had a higher recurrence risk than PerAF (HR, 2.22; 95% CI, 1.42-3.47). In LsAF >2.4 years, the PVI-plus strategy showed advantages over the PVI-alone strategy (HR, 0.36; 95% CI, 0.14-0.89). However, the interaction effect between LsAF 1-2.4 years and LsAF >2.4 years did not reach statistical significance (P = .116). CONCLUSION: Whereas LsAF 1-2.4 years has similar outcomes to those of PerAF, LsAF >2.4 years was linked to higher arrhythmia recurrence risks. For LsAF >2.4 years, the PVI-plus strategy showed a potential to be superior to the PVI-alone strategy.

Uplift modeling to identify patients who require extensive catheter ablation procedures among patients with persistent atrial fibrillation.

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.

The WATCH-DM risk score estimates clinical outcomes in type 2 diabetic patients with heart failure with preserved ejection fraction.

The coexistence of heart failure is frequent and associated with higher mortality in patients with type 2 diabetes (T2DM), and its management is a critical issue. The WATCH-DM risk score is a tool to predict heart failure in patients with type 2 diabetes mellitus (T2DM). We investigated whether it could estimate outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF). The WATCH-DM risk score was calculated in 418 patients with T2DM hospitalized for HFpEF (male 49.5%, age 80 ± 9 years, HbA1c 6.8 ± 1.0%), and they were divided into the "average or lower" (≤ 10 points), "high" (11-13 points) and "very high" (≥ 14 points) risk groups. We followed patients to observe all-cause death for 386 days (median). We compared the area under the curve (AUC) of the WATCH-DM score for predicting 1-year mortality with that of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and of the Barcelona Bio-Heart Failure Risk (BCN Bio-HF). Among the study patients, 108 patients (25.8%) had average or lower risk scores, 147 patients (35.2%) had high risk scores, and 163 patients (39.0%) had very high risk scores. The Cox proportional hazard model selected the WATCH-DM score as an independent predictor of all-cause death (HR per unit 1.10, 95% CI 1.03 to 1.19), and the "average or lower" risk group had lower mortality than the other groups (p = 0.047 by log-rank test). The AUC of the WATCH-DM for 1-year mortality was 0.64 (95% CI 0.45 to 0.74), which was not different from that of the MAGGIC score (0.72, 95% CI 0.63 to 0.80, p = 0.08) or that of BCN Bio-HF (0.70, 0.61 to 0.80, p = 0.25). The WATCH-DM risk score can estimate prognosis in T2DM patients with HFpEF and can identify patients at higher risk of mortality.

Initial results of transcatheter modification of left atrial appendage by obliteration with device in patients with nonvalvular atrial fibrillation: Real-world data from the TERMINATOR registry.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) has increased for those who need alternative to long-term anticoagulation with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: From September 2019, after initiating WATCHMAN (Boston Scientific, Maple Grove, MN, USA) device implantation, we established Transcatheter Modification of Left Atrial Appendage by Obliteration with Device in Patients from the NVAF (TERMINATOR) registry. Utilizing 729 patients' data until January 2022, we analyzed percutaneous LAAC data regarding this real-world multicenter prospective registry. A total of 729 patients were enrolled. Average age was 74.9 years and 28.5 % were female. Paroxysmal AF was 37.9 % with average CHADS2 3.2, CHA2DS2-VASc 4.7, and HAS-BLED score of 3.4. WATCHMAN implantation was successful in 99.0 %. All-cause deaths were 3.2 %, and 1.2 % cardiovascular or unexplained deaths occurred during follow-up [median 222, interquartile range (IQR: 93-464) days]. Stroke occurred in 2.2 %, and the composite endpoint which included cardiovascular or unexplained death, stroke, and systemic embolism were counted as 3.4 % [median 221, (IQR: 93-464) days]. Major bleeding defined as BARC type 3 or 5 was seen in 3.7 %, and there was 8.6 % of all bleeding events in total [median 219, (IQR: 93-464) days]. CONCLUSIONS: These preliminary data demonstrated percutaneous LAAC with WATCHMAN device might have a potential to reduce stroke and bleeding events for patients with NVAF. Further investigation is mandatory to confirm the long-term results of this strategy using this transcatheter local therapy instead of life-long systemic anticoagulation.

Discrepant results of the total pacing prematurity in orthodromic reciprocating tachycardia with right bundle branch block.

The total pacing prematurity (TPP) is useful for distinguishing orthodromic reciprocating tachycardia (ORT) from atrioventricular nodal re-entrant tachycardia, but it may not be effective in patients with right bundle branch block (RBBB). We faced this challenge in an elderly woman, as RBBB and a prolonged transseptal conduction made it difficult to diagnose the tachycardia using the TPP. It is important to consider the presence or absence of RBBB when evaluating the results of the TPP.

Factors influencing the difference in dissolved ion inputs to the forest floor between deciduous and coniferous stands: comparison under high and low atmospheric deposition conditions.

It is necessary to clear the relationship between physical and vegetation factors on the processes governing dissolved ion inputs to the forest floor to estimate correctly the values of atmospheric input to the forest. This study identified the factors influencing the differences in dissolved ion inputs to the forest floor between coniferous evergreen and broad-leaved deciduous species by analyzing the phenological variations of dry deposition and canopy exchange calculated by the canopy budget model under a high-deposition site near the city of Tokyo and a low-deposition site 84 km further away. At low-deposition site, vegetation factors such as capture efficiency did not explain the differences in Na+ or Cl- dry deposition. Leaf physiological characteristics influenced the differences in the Mg2+ and Ca2+ canopy leaching values, and phenology, leaf wettability, and diffusion processes from water film into leaves influenced the differences in NH4+ and NO3- input processes between tree types. At the high-deposition site, differences in the dry deposition of Na+, SO42-, Cl-, Mg2+, Ca2+, NH4+, and NO3- between tree types were influenced by differences in capture efficiency between coniferous and broad-leaved canopies in the leafed period and by the absence of leaves in deciduous species after leaf fall. These results indicated that atmospheric deposition affected the capture efficiency of coniferous trees for dry deposition and enhanced the difference of dissolved ion inputs to the forest floor between coniferous and deciduous species.

Influence of ultrasound transmit frequency on measurement of global longitudinal strain on 2D speckle tracking echocardiography.

The reproducibility of longitudinal strain measured by 2D speckle tracking echocardiography (2DSTE) may be affected by ultrasound settings. This study investigated the effect of transmit ultrasound frequency on global longitudinal strain (GLS) by 2DSTE. Apical, 2- and 4-chamber, and long-axis views were obtained in consecutive 162 patients using Philips ultrasound devices. Three different frequency presets were used sequentially: high resolution (HRES, 1.9 to 2.1 MHz), general (HGEN, 1.6 to 1.8 MHz), and penetration mode (HPEN, 1.3 to 1.6 MHz). GLS values were determined for each preset using the Philips Q-station software, resulting in GLS-HRES, GLS-HGEN, and GLS-HPEN. Among the 151 patients with successfully measured GLS, a significant difference in GLS was observed among the three presets (p < 0.0001). GLS-HRES (- 17.9 ± 4.4%) showed a slightly smaller magnitude compared to GLS-HGEN (- 18.8 ± 4.5%, p < 0.0001) and GLS-HPEN (- 18.8 ± 4.5%, p < 0.0001), with absolute differences of 1.1 ± 1.0% and 1.1 ± 1.2%, respectively. This variation in GLS with frequency was evident in patients with both optimal (n = 104) and suboptimal (n = 47) image quality and remained consistent regardless of ultrasound devices, ischemic etiology, or ejection fraction. In conclusion, ultrasound frequency had only a modest effect on GLS measurements. GLS may be reliably assessed in most cases regardless of the ultrasound frequency used.

Recurrence as isthmus-related atrial tachycardia: A cautionary point of low-voltage area homogenization of persistent atrial fibrillation.

A 66-year-old female underwent persistent atrial fibrillation ablation. After pulmonary vein isolation and homogenization of low-voltage areas (LVAs), atrial tachycardia (AT) was not induced at the first session; however, it recurred one year after the procedure. During the second session, the extensive LVAs were distributed in the same area of the left atrial anterior wall and expanded possibly due to the previous LVA homogenization. The activation map revealed a macroreentrant AT circuit with the critical isthmus between the isolated right superior pulmonary vein and homogenized LVAs. Although the Ripple map algorithm failed to visualize dynamic bars, extremely low voltage and fractionated potentials (amplitude, 0.04 mV) were observed at the isthmus. Currently, there are various procedural endpoints of LVA-guided ablation (e.g. local electrogram reduction > 50 % or <0.1 mV in amplitude). In this case, incomplete transmural lesions may have led to slow conduction, which could have become an AT substrate. In cases with extensive LVAs on the left atrial anterior wall, eliminating any potential channels may be important for preventing future iatrogenic ATs. LVA-guided ablation should be performed on an individual basis, considering the potential benefits and harms based on the extent and location of LVAs. Learning objective: Currently, the procedural endpoint of low-voltage area (LVA)-guided ablation varies across studies. Because any low-voltage potentials, except scars, can cause slow conduction, LVA-guided ablation with an endpoint of local electrogram voltage reduction can unintentionally generate an iatrogenic slow conduction isthmus. LVA-guided ablation should be individually performed, considering the potential benefits and harms based on the extent and location of LVAs.

Catheter ablation of malignant atrial fibrillation as palliative therapy for end-stage heart failure: A case report.

Recent randomized controlled trials have demonstrated the superiority of atrial fibrillation (AF) ablation to medical therapy in reducing mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction, but patients with end-stage HF were often excluded. A 64-year-old man diagnosed with dilated cardiomyopathy was hospitalized due to worsening HF and incident AF. An echocardiographic examination revealed the left ventricular end-diastolic diameter of 90 mm and left ventricular ejection fraction of 12 %. Cardioversion was performed to restore sinus rhythm, but intermittent transitions to AF caused the patient hemodynamic instability and mental distress. We carefully performed AF ablation, and sinus rhythm was maintained thereafter. After cardiac rehabilitation, he was successfully discharged home. However, he was re-hospitalized due to worsening HF 6 months post-AF ablation, and he eventually passed away. While AF ablation cannot prevent the progression of inherent cardiomyopathy, it can improve the quality of life even for patients with end-stage HF. However, the effect was temporary and considered a palliative treatment. This case highlights the potential benefits and limitations of AF ablation in end-stage HF patients and the need for further research to establish the optimal treatment for this population. Learning objective: Atrial fibrillation ablation can restore sinus rhythm and improve the quality of life even in some patients with end-stage heart failure (HF). However, it cannot prevent the progression of inherent cardiomyopathy. In the era of interventional HF therapy, catheter ablation may have a palliative role in reducing patient distress caused by life-threatening arrhythmias in patients with end-stage HF.

Long-Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST-PVI Trial.

Background An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results We conducted an extended follow-up of the multicenter randomized controlled EARNEST-PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12-month rhythm outcomes in patients with persistent AF between patients randomized to a PVI-alone strategy (n=248) or PVI-plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow-up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on-treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI-plus group than the PVI-alone group (29.0% versus 37.5%, P=0.036). On-treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, P=0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, P=0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, P<0.0001). Conclusions Left atrial ablation in addition to PVI was efficacious during 3-year follow-up. Linear ablation was superior to other ablation strategies but may increase iatrogenic ATs. Registration URL: http://www.umin.ac.jp/ctr/index-j.htm; Unique identifier: UMIN000019449.