Ablation Strategy Research Articles

Role of impedance drop and lesion size index (LSI) to guide catheter ablation for atrial fibrillation.

When using lesion size index (LSI) to guide catheter ablation, it is unclear what combination of power, contact force and time would be preferable to use and what LSI target value to aim for. This study aimed at identifying desirable ablation settings and LSI targets by using tissue impedance drop as indicator of lesion formation. Consecutive patients, undergoing their first left atrial (LA) catheter ablation for atrial fibrillation, with radiofrequency energy (RF) powers of 20, 30 and 40W were enrolled. Tissue impedance, contact force (CF), Force Time Integral (FTI) and LSI values were continuously recorded during ablation and sampled at 100Hz. Mean CF and Contact Force Variability (CFV) were calculated for every lesion. The effect of RF power, ablation time, CF and CFV on impedance drop and LSI were assessed. A total of 3258 lesions were included in the analysis. For any target LSI value, use of higher RF powers translated into progressively higher impedance drops. The impact of lower CF and higher CFV on impedance drop was more relevant when using lower powers. Target LSI values corresponding to maximum impedance drop were identified depending on RF power, mean CF and CFV used. Even in the context of an LSI-guided ablation strategy, use of lower or higher powers might lead to different lesion sizes. Different LSI targets might be needed depending on the combination of RF power, CF and CFV used for ablation. Incorporating indicators of catheter stability, like CFV, in the LSI formula could improve the predictive value of LSI for lesion size. Studies with clinical outcomes are required to confirm the clinical relevance of these findings.

Low-Voltage Area Ablation in Addition to Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52-0.81, p < 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] -5.32 min, 95% CI -19.01-8.46 min, p = 0.45), fluoroscopy time (MD -1.10 min, 95% CI -2.48-0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40-1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate.

Comparative Analysis of Clinical Outcomes of High-power, Short-duration Ablation versus Low-power, Long-duration Ablation Strategy in Patients with Atrial Fibrillation: A Comprehensive Umbrella Review of Meta-analyses.

Atrial fibrillation (AF) affects around 33 million people worldwide, rendering it a common cardiac arrhythmia. Catheter ablation (CA) has evolved as a leading therapeutic intervention for symptomatic AF. This umbrella review systematically evaluates existing systematic reviews and meta-analyses to assess the safety, efficacy, and potential of high-power, short-duration (HPSD) ablation as an alternative therapy option for AF. A thorough exploration was undertaken across PubMed, the Cochrane Library, and Embase to identify pertinent studies for inclusion in this umbrella review. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was employed to assess the overall certainty of the evidence comprehensively, and the quality of the incorporated reviews was meticulously evaluated through use of the AMSTAR 2 tool, the Cochrane Collaboration tool, and the Newcastle-Ottawa scale. In this study, we initially identified 35 systematic reviews and meta-analyses, narrowing them down to a final selection of 11 studies, which collectively integrated data from 6 randomized controlled trials and 26 observational studies. For primary efficacy outcomes, the HPSD approach led to a non-significant decrease in the risk of atrial tachyarrhythmia recurrence (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.70-1.12; I 2 = 90%; P = .31) and a significantly reduced risk of AF recurrence (RR, 0.53; 95% CI, 0.42-0.67; I 2 = 0%; P < .00001) compared to the low-power, long-duration (LPLD) approach. In terms of primary safety outcomes, the HPSD approach significantly reduced the risk of esophageal thermal injury (ETI) (RR, 0.71; 95% CI, 0.61-0.83; I 2 = 0%; P < .00001) and facilitated a non-significant decrease in the risk of other major complications (RR, 0.87; 95% CI, 0.73-1.03; I 2 = 0%; P = .10). In conclusion, HPSD therapy is safer and more effective than LPLD therapy, facilitating decreased AF recurrence rates along with reductions in ETI, total procedure duration, ablation number, ablation time, fluoroscopy time, and acute pulmonary vein reconnection.

Registro español de ablación con catéter. XXIII informe oficial de la Asociación del Ritmo Cardiaco de la Sociedad Española de Cardiología (2023)

Introduction and objectivesWe report the results of the 2023 Spanish catheter ablation registry. MethodsProcedural data were collected and incorporated into the REDCap platform by all participating centers through a specific form. ResultsThere were 104 participating centers in 2023 compared with 103 in 2022. In 2023, the total number of ablation procedures was 26 207, indicating a stabilization of the increase observed in 2022 following the pandemic. The increase was mainly due to procedures for atrial fibrillation (AF), with a total of 9942 ablations, representing 38% of all substrates. Notably, pulse-field ablation represented 10.3% of all AF ablation procedures, leading single-shot ablation strategies to outnumber point-by-point AF ablation for the first time in the history of the registry. Cavotricuspid isthmus ablation remained the second most targeted substrate (19% of all substrates, n=5067). The overall acute success rate remained high (97%), with a downward trend in the complication rate (1.6% vs 1.8% in 2022) and mortality rate (0.03%; n=7). Compared with 2022, there was a significant increase in procedures performed using electro-anatomical mapping and zero-fluoroscopy techniques for cavotricuspid isthmus ablation (52% vs 26%), AV node re-entrant tachycardia (48% vs 34%), and accessory pathways (62% vs 22%). We registered 466 ablations in pediatric patients. ConclusionsThe data indicate a stabilization in the post-pandemic increase in ablation procedures, with an absolute and relative increase in AF as the predominant substrate. Success rates remained stable with a modest reduction in complication and mortality rates.

Anatomic obstacles in cavotricuspid isthmus detected by modified 2D transthoracic echocardiography and long-term outcomes in radiofrequency ablation of typical atrial flutter.

Although radiofrequency ablation of the cavotricuspid isthmus (CTI), responsible for sustaining atrial flutter, is a highly effective procedure, in extended patients' observations following this procedure, more than every tenth becomes unsuccessful. Therefore, this study aimed to provide helpful information about the anatomy of the CTI in transthoracic echocardiography, which can aid in better planning of the CTI radiofrequency ablation in patients with typical atrial flutter. 56 patients with typical atrial flutter after radiofrequency ablation were evaluated at the end of the 24-month observation period. With substernal modified transthoracic echocardiographic (mTTE) evaluation, we identified four main anatomical obstacles impeding radiofrequency ablation. These obstacles were tricuspid annular plane systolic excursion, cavotricuspid isthmus length, cavotricuspid isthmus morphology, and the presence of a prominent Eustachian ridge/Eustachian valve. All intraprocedural radiofrequency ablation data were collected for analysis and correlated with anatomical data. In the 24-month observation period, freedom from atrial flutter was 67.86%. The mean length of the isthmus was 30.34 ± 6.67 mm. The isthmus morphology in 56 patients was categorized as flat (n = 27; 48.2%), concave (n = 10; 17.85%), and pouch (n = 19, 33.9%). A prominent Eustachian ridge was observed in 23 patients (41.1%). Lack of anatomical obstacles in mTTE evaluation resulted in 100% efficacy, while the presence of at least two obstacles significantly increased the risk of unsuccessful ablation with more than two (OR 12.31 p = 0.01). Generally, 8 mm electrodes were the most effective for non-difficult CTI, while 3.5 mm electrodes used with a 3D system had highest performance for complex CTI. Notably, aging was the only factor that worsened the long-term outcome (OR 1.07 p = 0.044). Preoperative usage of mTTE evaluation helps predict difficulty in cavotricuspid isthmus radiofrequency ablation, thus allowing better planning of the radiofrequency ablation strategy using the most accurate radiofrequency ablation electrode.

Contact-force local impedance algorithm to guide effective pulmonary vein isolation in AF patients: 1-year outcome from an international multicenter clinical setting.

The combination of highly localized impedance (LI) and contact force (CF) may improve tissue characterization and lesion prediction during radiofrequency (RF) pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). We report the outcomes of our acute and long-term clinical evaluation of CF-LI-guided PVI in consecutive AF ablation cases from an international multicenter clinical setting. Three hundred twenty-four consecutive patients from 20 European centers undergoing RF catheter ablation with the Stablepoint™ catheter were enrolled in the CHARISMA registry. Of these, 275 had a minimum follow-up of 1year and were included in the primary analysis. The mean procedure duration was 115 ± 47min, and the mean fluoroscopy time was 9.9 ± 6min. At the end of the procedures, all PVs had been successfully isolated in all study patients. Minor complications were reported in 12 patients (4.4%). At 1year, 36 (13.1%) patients had had an AF recurrence, and freedom from antiarrhythmic drugs and AF recurrence was achieved in 228 (82.9%) patients. The recurrence rate was higher in patients with persistent AF (21/116, 18.1%) than in those with paroxysmal AF (15/159, 9.4%; p = 0.0459). On multivariate logistic analysis adjusted for baseline confounders, only time > 6months from first diagnosis of AF to ablation (HR = 2.93, 95%CI 1.03 to 8.36, p = 0.0459) was independently associated with recurrences. An ablation strategy for PVI guided by CF-LI technology proved safe and effective and resulted in a low recurrence rate of AF over 1-year follow-up, irrespective of the underlying AF type. Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice. (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998.

Catheter-related and clinical complications associated with QDOT MICROTM Ablation Catheter.

The QDOT MICROTM Ablation Catheter is a next-generation ablation catheter that allows for high-power ablation up to 90 watts. We aimed to assess AE associated with the QDOT MICROTM catheter using the MAUDE database. A MAUDE database search was conducted on May 25, 2024, to capture all AEs (since FDA approval) associated with this ablation catheter. A total of 302 AEs from November 23, 2022, to April 30, 2024, were reported including 148 (49%) catheter-related issues and 154 (51%) clinical complications. Among the catheter-related issues, physical catheter damage (74.3%, n = 110) was most common, followed by communication or display issue (10.8%, n = 16), irrigation issue (9.5%, n = 14), signal issue or artifact (3.4%, n = 5), and inaccurate temperature measurement (2.0%, n = 3). Regarding clinical complications, the most common AE was pericardial effusion (43.5%, n = 67), followed by char formation (11.7%, n = 18), catheter thrombosis (7.1%, n = 11), stroke (7.1%, n = 11), pericarditis (7.1%, n = 11), esophageal complications (6.5%, n = 10), phrenic nerve palsy (3.9%, n = 6), cardiac arrest (3.9%, n = 6), significant AV block (3.9%, n = 6), pulmonary vein stenosis (3.2%, n = 5), coronary artery spasm (1.3%, n = 2), and pulmonary embolism (0.6%, n = 1). There were 11 deaths (five related to esophageal complications, five related to cardiac arrest, and one related to pericardial effusion with cardiac tamponade). As high-power ablation strategy with novel ablation catheters is becoming more widely utilized, operators must be aware of potential catheter-related issues and clinical complications that may arise. More data are needed to further evaluate risks of these complications to improve the catheter's safety and efficacy.

A novel approach to terminate roof-dependent atrial flutter with epicardial conduction through septopulmonary bundle

Atrial flutter, a prevalent cardiac arrhythmia, is primarily characterized by reentrant circuits in the right atrium. However, atypical forms of atrial flutter present distinct challenges in terms of diagnosis and treatment. In this study, we examine three noteworthy clinical cases of atypical atrial flutter, which offer compelling evidence indicating the implication of the lesser-known Septopulmonary Bundle (SPB). This inference is based on the identification of distinct electrocardiographic patterns observed in these patients and their favorable response to catheter ablation, which is a standard treatment for atrial flutter. Remarkably, in each case, targeted ablation at the anterior portion of the left atrial roof effectively terminated the arrhythmia, thus providing further support for the hypothesis of SPB involvement. These insightful observations shed light on the potential significance of the SPB in the etiology of atypical atrial flutter and introduce a promising therapeutic target. We anticipate that this paper will stimulate further exploration into the role of the SPB in atrial flutter and pave the way for the development of targeted ablation strategies.

A Novel Combination Strategy of Ultrasound-Guided Percutaneous Radiofrequency Ablation and Corticosteroid Injection for Treating Recalcitrant Plantar Fasciitis: A Retrospective Comparison Study.

The best treatment yielding clinical benefits was still equivocal and controversial for the treatment of recalcitrant plantar fasciitis (PF). This study aimed to propose a novel combination strategy of ultrasound-guided percutaneous radiofrequency ablation (RFA) and corticosteroid injection (CI) for recalcitrant PF, and to compare its therapeutic effects with CI alone and continued conservative management. We retrospectively reviewed consecutive patients with recalcitrant PF who underwent combined strategy (RFA + CI), CI alone, and continue conservative treatment at our institution between October 2021 and February 2023. The technical pearls were described elaborately. A comparison of demographic data and clinical outcomes, including visual analog scale (VAS), Ankle-Hindfoot Scale (AOFAS-AHS), and plantar fascia thickness, were conducted among the three groups. Seventy-one eligible patients were enrolled in this study, with 17 in the combined strategy group, 25 in the CI group, and 29 in the continued conservative treatment group. Both the combined strategy group and the CI group showed significant improvements in VAS scores, AOFAS-AHS scores, and significant reductions in plantar fascia thickness during the 12-month follow-up period compared to those preoperatively (P < 0.05). The combined strategy group achieved comparable immediate pain relief to the CI group after the intervention ([25.7 ± 15.7] vs. [20.6 ± 17.6], P = 0.850). However, the combined strategy group demonstrated superior improvement in symptom and function compared to the CI group at the 3-month (VAS: [21.9 ± 13.5] vs. [39.6 ± 20.4]; AOFAS-AHS: [77.9 ± 12.4] vs. [60.5 ± 17.4], P < 0.05) and 12-month follow-up (VAS: [15.7 ± 12.0] vs. [56.8 ± 17.5]; AOFAS-AHS: [84.5 ± 10.7] vs. [53.8 ± 12.4], P < 0.05). Obvious adverse effects or complications were not identified in either group, while two cases (11.8%) in the combined strategy group and five cases (20.0%) in the CI group experienced unsatisfactory symptom remission. We introduced and detailed a novel combination strategy involving ultrasound-guided percutaneous RFA and CI for treating recalcitrant PF. The strategy is both effective and safe in alleviating pain and enhancing function throughout the entire treatment course.

Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.

Intracardiac echocardiography guided anatomical ablation of the arcuate ridge for drug refractory inappropriate sinus tachycardia.

Inappropriate sinus tachycardia (IST) is a common condition with frequently not tolerated beta-blockers or ivabradine and a high rate of complication in ablation strategy; we describe an alternative anatomical approach of sinus node (SN) modulation. This retrospective study describes a case series of 6 patients from two centers diagnosed with symptomatic IST undergoing SN ablation. The mean age was 40.6 ± 13.9 years; five of the six patients were female, 100% of patients reported heart palpitations, and 66% reported dizziness, the average heart rate(HR) on a 24-h Holter was 93.2 ± 7.9 bpm. HR during the first stage of a stress test using a standard Bruce protocol was 150 ± 70 bpm, The average HR on 24-h Holter postablation was 75 ± 5.6 bpm, the sinus rate HR during stage 1 of a Bruce protocol exercise stress test was 120 ± 10 bpm. This is the first case series reporting the acute and long-term results of a novel anatomical approach for SN modulation to treat IST targeting the arcuate ridge(AR) under intracardiac echography(ICE) guidance. The novel anatomic ICE-guided catheter ablation approach aimed to identify the earliest activation at the AR with an extension of RF lesions towardits septal region seems effective and safe to modulate the SN in symptomatic patients with IST refractory to medical treatment.

Accuracy of Different Surface Electrocardiogram Algorithms for Localization of Accessory Pathway in Comparison to Invasive Electrophysiological Localization: An Observational Study

Introduction: Detection of accessory pathway (AP) on surface ECG in sinus rhythm helps in the diagnosis of Wolff-Parkinson-White Syndrome (WPW Syndrome), Catheter ablation of AP was indicated in symptomatic patients with preexcitation. Pre-ablation AP localization inferred from the 12-lead surface electrocardiogram (ECG) facilitates a tailored ablation strategy; there by specific risk can be properly assessed. As they are based on pre-excitation in the basal state, available algorithms can lead to complex and ambiguous analysis, mostly due to the variable influence of the AP over QRS morphology. Though various algorithms on surface ECG are available to predict the site of AP on surface ECG, but none of them are accurate. So, we have compared the accuracy of different algorithms in predicting the AP localization in comparison to electrophysiological study (EPS) diagnosis. Methodology: This retrospective observational study cohort consisted of 100 consecutive patients above 15 years of age presented to the tertiary care center with the history of palpitations or for assessment of a manifest AP. Accessory pathways were identified according to the site where successful radiofrequency energy was applied. Arruda algorithm, Milstein algorithm, Fitzpatrick algorithm and Pambrun algorithm were applied on a sinus rhythm manifest preexcited ECG to predict the AP localization by two independent investigators who are unaware of site of successful catheter ablation. Then those were compared with the EPS localization to test the accuracy of individual algorithm. Then Cohen’s Kappa was run to determine if there was agreement between any of the four different algorithms with EPS using SPSS version 20.0. Results: In the study population of 100 patients, male to female ratio of study population was 1.6:1, with a mean age of presentation 43.86 ± 11.4 years with the most common age group of 31 to 45 year. when the AP locations were categorized based on EP Study 56 percent of the AP were found on the left side while 43 percent of the AP were found on right side, 77 percent of the AP were septal pathways. Among the leftsided pathways, left anteroseptal constitutes majority followed by left posteroseptal pathway. On right side majority were in right posteroseptal location in our study. Based on 4 surface ECG algorithms AP was localized and each algorithm was compared with invasive EPS localization for accuracy using Cohen’s Kappa agreement analysis. As per agreement analysis the kappa value for Milstein, Pambrun algorithm, Fitzpatrik and Arruda were 0.188, 0.343, 0.441, and 0.645 respectively. It was found that Arruda algorithm had moderate strength of agreement with the findings of EPS (κ = 0.645). This is the proportion of agreement over and above chance agreement and which was statistically significant and the strongest among all the four algorithms. Conclusion: Our study has compared the accuracy of 4 surface ECG algorithms in predicting the accessory pathway localization with the EPS; it has demonstrated that the Arruda algorithm is more precise and accurate among the available algorithms followed by Fitzpatrik, Pambrun algorithm and Milstein algorithm, Knowing the pathway prior to ablation allows for optimal procedure preparation, mapping pathways that are difficult to find and finally may lessen the catheter-related injury and shortens the procedural time.

A cost-consequence analysis comparing three cardiac ablation strategies for the treatment of paroxysmal atrial fibrillation

Background and aims Cardiac ablation is a well-established method for treating atrial fibrillation (AF). Pulsed field ablation (PFA) is a non-thermal therapeutic alternative to radiofrequency ablation (RFA) and cryoballoon ablation (CRYO). PFA uses high-voltage electric pulses to target cells. The present analysis aims to quantify the costs, outcomes, and resources associated with these three ablation strategies for paroxysmal AF. Methods Real-world clinical data were prospectively collected during index hospitalization by three European medical centers (Belgium, Germany, the Netherlands) specialized in cardiac ablation. These data included procedure times (pre-procedural, skin-to-skin and post-procedural), resource use, and staff burden. Data regarding complications associated with each of the three treatment options and redo procedures were extracted from the literature. Costs were collected from hospital economic formularies and published cost databases. A cost-consequence model from the hospital perspective was built to estimate the impact of the three treatment options in terms of effectiveness and costs. Results Across the three centers, N = 91 patients were included over a period of 12 months. A significant difference was seen in pre-procedural time (mean ± SD, PFA: 13.6 ± 3.7 min, CRYO: 18.8 ± 6.6 min, RFA: 20.4 ± 6.4 min; p < .001). Procedural time (skin-to-skin) was also different across alternatives (PFA: 50.9 ± 22.4 min, CRYO: 74.5 ± 24.5 min, RFA: 140.2 ± 82.4 min; p < .0001). The model reported an overall cost of €216,535 per 100 patients treated with PFA, €301,510 per 100 patients treated with CRYO and €346,594 per 100 patients treated with RFA. Overall, the cumulative savings associated with PFA (excluding kit costs) were €850 and €1,301 per patient compared to CRYO and RFA, respectively. Conclusion PFA demonstrated shorter procedure time compared to CRYO and RFA. Model estimates indicate that these time savings result in cost savings for hospitals and reduce outlay on redo procedures. Clinical practice in individual hospitals varies and may impact the ability to transfer the results of this analysis to other settings.

Assessing the arrhythmogenic propensity of fibrotic substrate using digital twins to inform a mechanisms-based atrial fibrillation ablation strategy

Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment—pulmonary vein isolation—has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients’ AF burden.

PPARG is dispensable for bovine embryo development up to tubular stages†.

Following blastocyst hatching, ungulate embryos undergo a prolonged preimplantation period termed conceptus elongation. Conceptus elongation constitutes a highly susceptible period for embryonic loss, and the embryonic requirements during this process are largely unknown, but multiple lipid compounds have been identified in the fluid nourishing the elongating conceptuses. Peroxisome proliferator-activated receptors mediate the signaling actions of prostaglandins and other lipids, and, between them, PPARG has been pointed out to play a relevant role in conceptus elongation by a functional study that depleted PPARG in both uterus and conceptus. The objective of this study has been to determine if embryonic PPARG is required for bovine embryo development. To that aim, we have generated bovine PPARG knock-out embryos in vitro using two independent gene ablation strategies and assessed their developmental ability. In vitro development to Day 8 blastocyst was unaffected by PPARG ablation, as total, inner cell mass, and trophectoderm cell numbers were similar between wild-type and knock-out D8 embryos. In vitro post-hatching development to D12 was also comparable between different genotypes, as embryo diameter, epiblast cell number, embryonic disk formation, and hypoblast migration rates were unaffected by the ablation. The development of tubular stages equivalent to E14 was assessed in vivo, following a heterologous embryo transfer experiment, observing that the development of extra-embryonic membranes and of the embryonic disk was not altered by PPARG ablation. In conclusion, PPARG ablation did not impaired bovine embryo development up to tubular stages.

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

BackgroundExtensive 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. MethodsThis 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. ResultsThe 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. ConclusionsFor 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.

Initial real-world data on catheter ablation in patients with persistent atrial fibrillation using the novel lattice-tip focal pulsed-field ablation catheter.

Technological advancements have contributed to the enhanced precision and lesion flexibility in pulsed-field ablation (PFA) by integrating a three-dimensional mapping system combined with a point-by-point ablation strategy. Data regarding the feasibility of this technology remain limited to some clinical trials. This study aims to elucidate initial real-world data on catheter ablation utilizing a lattice-tip focal PFA/radiofrequency ablation (RFA) catheter in patients with persistent atrial fibrillation (AF). Consecutive patients who underwent catheter ablation for persistent AF via the lattice-tip PFA/RFA catheter were enrolled. We evaluated acute procedural data including periprocedural data as well as the clinical follow-up within a 90-day blanking period. In total, 28 patients with persistent AF underwent AF ablation either under general anaesthesia (n = 6) or deep sedation (n = 22). In all patients, pulmonary vein isolation was successfully achieved. Additional linear ablations were conducted in 21 patients (78%) with a combination of successful anterior line (n = 13, 46%) and roof line (n = 19, 68%). The median procedural and fluoroscopic times were 97 (interquartile range, IQR: 80-114) min and 8.5 (IQR: 7.2-9.5) min, respectively. A total of 27 patients (96%) were interviewed during the follow-up within the blanking period, and early recurrent AF was documented in four patients (15%) including one case of recurrent AF during the hospital stay. Neither major nor minor procedural complication occurred. In terms of real-world data, our data confirmed AF ablation feasibility utilizing the lattice-tip focal PFA/RFA catheter in patients with persistent AF.

Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.

Complementary use of conduction system pacing techniques for the “pace and ablate” strategy in permanent atrial fibrillation - a case report

Abstract Introduction The feasibility of the conduction system pacing combined with atrioventricular node ablation was demonstrated in patients with atrial fibrillation in whom rate control can’t be achieved with medication and heart failure. Clinical case We present a case of an 82-year-old man with a personal history of permanent atrial fibrillation, admitted with symptoms of heart failure. The resting electrocardiogram showed a very fast ventricular response, and the echocardiography showed a depressed left ventricular function, raising the suspicion of a tachycardia-mediated cardiomyopathy. Since the patient was on maximum doses of atrioventricular nodal-blocking drugs, we opted for a physiological pacing and atrioventricular node ablation strategy. First, the His bundle capture was achieved at low pacing thresholds, and ablation of the atrioventricular node was attempted. Unfortunately, after several failed attempts, an acute increase in the His bundle capture threshold was noted, suggesting inadvertent tissue ablation beneath the pacing lead. In this scenario, we removed the lead from the His bundle area and achieved optimal left bundle branch area pacing. With the lead in this position, atrioventricular node ablation was performed during the first attempt. At the six-month follow-up, there was no recovery of atrioventricular node conduction. Device interrogation revealed stable pacing and sensing parameters, and there was a significant improvement in clinical status and left ventricular function. Conclusions Mastering both His bundle pacing and left bundle branch area pacing offers the potential to overcome intraprocedural challenges, giving alternative strategies to achieve physiological pacing. These approaches can be used interchangeably based on the evolving dynamics of the procedure and the patient’s specific needs.

Targeting Wavefront Discontinuity Lines for Scar-Related Ventricular Tachycardia Ablation: A Novel Functional Substrate Ablation Approach

BackgroundThe boundaries of critical isthmuses for re-entrant ventricular tachycardia (VT) are formed by wavefront discontinuities (fixed lines of block, slow propagation, and rotational propagation) seen during baseline rhythm. It is unknown whether wavefront discontinuities can be automatically identified and targeted for ablation using electroanatomic mapping systems. ObjectivesThe purpose of this study was to assess the electrophysiologic characteristics of automatically projected wavefront discontinuity lines (WADLs) and outcomes of an ablation strategy targeting WADLs in a mixed cohort of VT patients. MethodsLate activation substrate maps were analyzed from 1 or more baseline rhythm wavefronts. WADLs were identified using the Carto Extended Early Meets Late module. Number, total length, and distance to critical VT sites were measured. VT recurrence and VT-free survival were followed. ResultsIn total, 49 patients underwent 52 ablations with 71 unique substrate maps analyzed (18.8% epicardial; 62.0% right ventricular paced, 28.2% sinus rhythm, 9.9% left ventricular paced). A total of 28 VT critical sites were identified in 24 patients. WADLs were present in 49 of 71 (69.0%) maps. WADLs were present regardless of cardiomyopathy etiology, mapping wavefront, or surface. At a WADL threshold of 30%, 73.9% of critical VT sites were in close proximity (≤15 mm) to a WADL. VT-free survival was 62% at 1 year, with a competing risk model estimating a 1-year risk of VT recurrence of 23%. ConclusionsWADLs can be automatically projected in a majority of patients in a mixed cohort of cardiomyopathy etiology, mapped wavefronts, and myocardial surfaces mapped. Targeting WADLs results in low rate of VT recurrence at 1 year.