ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway.

One of the independent risk factors for atrial fibrillation is diabetes mellitus (DM); however, the underlying mechanisms causing atrial fibrillation in DM are unknown. The underlying mechanism of Atrogin-1-mediated SK2 degradation and associated signaling pathways are unclear. The aim of this study was to elucidate the relationship among reactive oxygen species (ROS), the NF-κB signaling pathway, and Atrogin-1 protein expression in the atrial myocardia of DM mice. We found that SK2 expression was downregulated comitant with increased ROS generation and enhanced NF-κB signaling activation in the atrial cardiomyocytes of DM mice. These observations were mimicked by exogenously applicating H2O2 and by high glucose culture conditions in HL-1 cells. Inhibition of ROS production by diphenyleneiodonium chloride or silencing of NF-κB by siRNA decreased the protein expression of NF-κB and Atrogin-1 and increased that of SK2 in HL-1 cells with high glucose culture. Moreover, chromatin immunoprecipitation assay demonstrated that NF-κB/p65 directly binds to the promoter of the FBXO32 gene (encoding Atrogin-1), regulating the FBXO32 transcription. Finally, we evaluated the therapeutic effects of curcumin, known as a NF-κB inhibitor, on Atrogin-1 and SK2 expression in DM mice and confirmed that oral administration of curcumin for 4 weeks significantly suppressed Atrogin-1 expression and protected SK2 expression against hyperglycemia. In summary, the results from this study indicated that the ROS/NF-κB signaling pathway participates in Atrogin-1-mediated SK2 regulation in the atria of streptozotocin-induced DM mice.

Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.

BACKGROUND: Alterations in the buffering of intracellular Ca2+, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca2+ buffering profile in persAF remains obscure. Therefore, we aimed to investigate the intracellular buffering of Ca2+ and its potential arrhythmogenic role in persAF. METHODS: Transmembrane Ca2+ fluxes (patch-clamp) and intracellular Ca2+ signaling (fluo-3-acetoxymethyl ester) were recorded simultaneously in myocytes from right atrial biopsies of sinus rhythm (Ctrl) and patients with persAF, alongside human atrial subtype induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Protein levels were quantified by immunoblotting of human atrial tissue and induced pluripotent stem cell-derived cardiac myocytes. Mouse whole heart and atrial electrophysiology were measured on a Langendorff system. RESULTS: Cytosolic Ca2+ buffering was decreased in atrial myocytes of patients with persAF because of a depleted amount of Ca2+ buffers. In agreement, protein levels of selected Ca2+ binding myofilament proteins, including cTnC (cardiac troponin C), a major cytosolic Ca2+ buffer, were significantly lower in patients with persAF. Small interfering RNA (siRNA)-mediated knockdown of cTnC (si-cTNC) in atrial iPSC-CM phenocopied the reduced cytosolic Ca2+ buffering observed in persAF. Si-cTnC treated atrial iPSC-CM exhibited a higher predisposition to spontaneous Ca2+ release events and developed action potential alternans at low stimulation frequencies. Last, indirect reduction of cytosolic Ca2+ buffering using blebbistatin in an ex vivo mouse whole heart model increased vulnerability to tachypacing-induced atrial arrhythmia, validating the direct mechanistic link between impaired cytosolic Ca2+ buffering and atrial arrhythmogenesis. CONCLUSIONS: Our findings suggest that loss of myofilament proteins, particularly reduced cTnC protein levels, causes diminished cytosolic Ca2+ buffering in persAF, thereby potentiating the occurrence of spontaneous Ca2+ release events and atrial fibrillation susceptibility. Strategies targeting intracellular buffering may represent a promising therapeutic lead in persAF management.

Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder, often occurring in the setting of atrial distension and elevated myocardialstretch. While various mechano-electrochemical signal transduction pathways have been linked to AF development and progression, the underlying molecular mechanisms remain poorly understood, hampering AF therapies. In this review, we describe different aspects of stretch-induced electro-anatomical remodeling as seen in animal models and in patients with AF. Specifically, we focus on cellular and molecular mechanisms that are responsible for mechano-electrochemical signal transduction and the development of ectopic beats triggering AF from pulmonary veins, the most common source of paroxysmal AF. Furthermore, we describe structural changes caused by stretch occurring before and shortly after the onset of AF as well as during AF progression, contributing to longstanding forms of AF. We also propose mechanical stretch as a new dimension to the concept "AF begets AF", in addition to underlying diseases. Finally, we discuss the mechanisms of these electro-anatomical alterations in a search for potential therapeutic strategies and the development of novel antiarrhythmic drugs targeted at the components of mechano-electrochemical signal transduction not only in cardiac myocytes, but also in cardiac non-myocyte cells.

Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance, often treated via electrical cardioversion. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs, suggesting that defects in contractility occur in AFib and are revealed upon restoration of rhythm. This project aims to define the contractile remodeling that occurs in AFib. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared with sinus rhythm atria. Atrial cardiomyocytes show reduced force of contraction, decreased resting tension, and increased calcium sensitivity in skinned single cardiomyocyte studies. These alterations correlated with degradation of myofilament proteins including myosin heavy chain altering force of contraction, titin altering resting tension, and troponin I altering calcium sensitivity. We measured degradation of other myofilament proteins, including cardiac myosin binding protein C and actinin, that show degradation products in the AFib samples that are absent in the sinus rhythm atria. Many of the degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. These results provide an understanding of the contractile remodeling that occurs in AFib and provide insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.NEW & NOTEWORTHY Atrial fibrillation is the most common cardiac rhythm disorder, and remodeling during atrial fibrillation is highly variable between patients. This study has defined the biophysical changes in contractility that occur in atrial fibrillation along with identifying potential molecular mechanisms that may drive this remodeling. This includes proteolysis of several myofilament proteins including titin, troponin I, myosin heavy chain, myosin binding protein C, and actinin, which is consistent with the observed contractile deficits.

Association between atrial fibrillation and heart failure patient reported outcomes across the ejection fraction spectrum.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS: This is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group). RESULTS: In TOPCAT, among 1,710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI -7.21: -0.74) at 48 months, with a significant AF status by time interaction (P = .03). In HF-ACTION, among 1,814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI -6.21: -1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score. CONCLUSION: Ιn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.

Adjunctive low-voltage area ablation for patients with atrial fibrillation: An updated meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy and safety of adjunctive low-voltage area (LVA) ablation on outcomes of catheter ablation (CA) for atrial fibrillation (AF) remains uncertain. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing CA with versus without LVA ablation for patients with AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. Our primary endpoint was recurrence of atrial tachyarrhythmia (ATA), including AF, atrial flutter, or atrial tachycardia. We used R version 4.3.1 for all statistical analyses. RESULTS: Our meta-analysis included 10 RCTs encompassing 1780 patients, of whom 890 (50%) were randomized to LVA ablation. Adjunctive LVA ablation significantly reduced recurrence of ATA (RR 0.76; 95% CI 0.67-0.88; p < .01) and reduced the number of redo ablation procedures (RR 0.54; 95% CI 0.35-0.85; p < .01), as compared with conventional ablation. Among 691 (43%) patients with documented LVAs on baseline substrate mapping, adjunctive LVA ablation substantially reduced ATA recurrences (RR 0.57; 95% CI 0.38-0.86; p < .01). There was no significant difference between groups in terms of periprocedural adverse events (RR 0.78; 95% CI 0.39-1.56; p = .49). CONCLUSIONS: Adjunctive LVA ablation is an effective and safe strategy for reducing recurrences of ATA among patients who undergo CA for AF.

Nonpharmacologic rate control of postoperative atrial fibrillation in the canine sterile pericarditis model.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is common following open heart surgery, and is associated with significant morbidity. Medications used for ventricular rate control of POAF may not be effective in controlling rapid ventricular rates during the postoperative period because of increased sympathetic tone. The purpose of this study was to develop nonpharmacologic rate control of POAF by atrioventricular node (AVN) fat pad stimulation using clinically available temporary pacing wires in the canine sterile pericarditis model. METHODS: We studied 10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-3. The AVN fat pad stimulation (amplitude 2-15 mA; frequency 20 Hz; pulse width 0.03-0.2 ms) was performed during sustained POAF (>5 min). We measured ventricular rate and inefficient ventricular contractions during sustained POAF and compared it with and without AVN fat pad stimulation. Also, the parameters of AVN fat pad stimulation to achieve a rate control of POAF were measured over the postoperative days. RESULTS: Eleven episodes of sustained POAF were induced in 5/10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-2. During POAF, the AVN fat pad stimulation decreased the ventricular rate from 178 ± 52 bpm to 100 ± 8 bpm in nine episodes. Nonpharmacologic rate control therapy successfully controlled the ventricular rate and eliminated inefficient ventricular contractions during POAF for the duration of the AVN fat pad stimulation. The AVN fat pad stimulation output remained relatively stable over the postoperative days. CONCLUSION: During sustained POAF, nonpharmacologic rate control by AVN fat pad stimulation effectively and safely controlled rapid ventricular rates throughout the postoperative period.

Consistency of ablations with trainee and increasing independence during fellowship training-Analysis of ablation data by CARTONET.

INTRODUCTION: Training in clinical cardiac electrophysiology (CCEP) involves the development of catheter handling skills to safely deliver effective treatment. Objective data from analysis of ablation data for evaluating trainee of CCEP procedures has not previously been possible. Using the artificial intelligence cloud-based system (CARTONET), we assessed the impact of trainee progress through ablation procedural quality. METHODS: Lesion- and procedure-level data from all de novo atrial fibrillation (AF) and cavotricuspid isthmus (CTI) ablations involving first-year (Y1) or second-year (Y2) fellows across a full year of fellowship was curated within Cartonet. Lesions were automatically assigned to anatomic locations. RESULTS: Lesion characteristics, including contact force, catheter stability, impedance drop, ablation index value, and interlesion time/distance were similar over each training year. Anatomic location and supervising operator significantly affected catheter stability. The proportion of lesion sets delivered independently and of lesions delivered by the trainee increased steadily from the first quartile of Y1 to the last quartile of Y2. Trainee perception of difficult regions did not correspond to objective measures. CONCLUSION: Objective ablation data from Cartonet showed that the progression of trainees through CCEP training does not impact lesion-level measures of treatment efficacy (i.e., catheter stability, impedance drop). Data demonstrates increasing independence over a training fellowship. Analyses like these could be useful to inform individualized training programs and to track trainee's progress. It may also be a useful quality assurance tool for ensuring ongoing consistency of treatment delivered within training institutions.

Impact of weight adjusted high frequency low tidal volume ventilation and atrial pacing in lesion metrics in high-power short-duration ablation: Results of a pilot study.

INTRODUCTION: Lesion size index (LSI) was introduced with the use of Tacticath™ and as a surrogate of lesion quality. The metric used to achieve the predetermined values involves combined information of contact force (CF), power and radiofrequency time. Rapid atrial pacing (RAP) and high-frequency low-tidal volume ventilation (HFLTV) independently or in combination improve catheter stability and CF and quality of lesions. Data of the impact of body weight adjusted HFLTV ventilation strategy associated with RAP in the lesion metrics still lacking. The study aimed to compare the results of high-power short-duration (HPSD) atrial fibrillation ablation using simultaneous weight adjusted HFLTV and RAP and standard ventilation (SV) protocol. METHODS: Prospective, nonrandomized study with 136 patients undergoing de novo ablation divided into two groups; 70 in RAP (100 ppm) + HFLTV with 4 mL/kg of tidal volume and 25 breaths/min (group A) and 66 patients with SV in intrinsic sinus rhythm (group B). Ablation using 50 W, CF of 5-10 g/10-20 g and 40 mL/minute flow rate on the posterior and anterior left atrial wall, respectively. RESULTS: No procedure-related complications. Group A: Mean LSI points 70 ± 16.5, mean total lower LSI 3.4 ± 0.5, mean total higher LSI 8.2 ± 0.4 and mean total LSI 5.6 ± 0.6. Anterior and posterior wall mean total LSI was 6.0 ± 0.4 and 4.2 ± 0.3, respectively. Mean local impedance drop (LID) points were 118.8 ± 28.4, mean LID index (%) 12.9 ± 1.5, and mean LID < 12% points 55.9 ± 23.8. Anterior and posterior wall mean total LID index were 13.6 ± 2.0 and 11.9 ± 1.7, respectively. Recurrence in 11 (15.7%) patients. Group B: Mean LSI points 56 ± 2.7, mean total lower LSI 2.9 ± 0.7, mean total higher LSI 6.9 ± 0.9, and mean total LSI 4.8 ± 0.8. Anterior and posterior wall mean total LSI was 5.1 ± 0.3 and 3.5 ± 0.5, respectively. Mean LID points were 111.4 ± 21.5, mean LID index (%) 11.4 ± 1.2, and mean LID < 12% points 54.9 ± 25.2. Anterior and posterior wall mean total LID index were 11.8 ± 1.9 and 10.3 ± 1.7, respectively. Recurrence in 14 (21.2%) patients. Mean follow up was 15.2 ± 4.4 months. CONCLUSION: Weight adjusted HFLTV ventilation with RAP HPSD ablation produced lower recurrence rate and better LSI and LID parameters in comparison to SV and intrinsic sinus rhythm.

Early ablation of newly diagnosed paroxysmal atrial fibrillation (NEWPaAF) versus newly diagnosed persistent atrial fibrillation (NEWPeAF): Comparison of patient populations and ablation outcomes.

INTRODUCTION: Little is known about very early atrial fibrillation (AF) ablation after first AF detection. METHODS: We evaluated patients with AF ablation <4 months from newly diagnosed paroxysmal AF (NEWPaAF) and newly diagnosed persistent AF (NEWPeAF). We compared the two patient populations and compared ablation outcomes to those undergoing later ablation. RESULTS: Ablation was done <4 months from AF diagnosis in 353 patients (135 = paroxysmal, 218 = persistent). Early ablation outcome was best for NEWPaAF versus NEWPeAF for initial (p = 0.030) but not final (p = 0.102) ablation. Despite recent AF diagnosis in both groups, they were clinically quite different. NEWPaAF patients were younger (64.3 ± 13.0 vs. 67.3 ± 10.9, p = 0.0020), failed fewer drugs (0.39 vs. 0.60, p = 0.007), had smaller LA size (4.12 ± 0.58 vs. 4.48 ± 0.59 cm, p < 0.0001), lower BMI (28.8 ± 5.0 vs. 30.3 ± 6.0, p = 0.016), and less CAD (3.7% vs. 11.5%, p = 0.007), cardiomyopathies (2.2% vs. 22.9%, p = 0.0001), hypertension (46.7% vs. 67.4%, p < 0.0001), diabetes (8.1% vs. 17.4%, p = 0.011) and sleep apnea (20.0% vs. 30.3%, p = 0.031). For NEWPaAF, early ablation AF-free outcome was no better than later ablation (p = 0.314). For NEWPeAF, AF-free outcomes were better for early ablation than later ablation (p < 0.0001). Delaying ablation allowed more strokes/TIAs in both AF types (paroxysmal p = 0.014, persistent p < 0.0001). CONCLUSIONS: Patients presenting for early ablation after newly diagnosed persistent AF have more pre-existing comorbidities and worse initial ablation outcomes than patients with NEWPaAF. For NEWPaAF, there was no advantage to early ablation, as long as the AF remained paroxysmal. For NEWPeAF, early ablation gave better outcomes than later ablation and they should undergo early ablation. For both AF types, waiting was associated with more neurologic events, suggesting all patients should consider earlier ablation.

Integrated dilator-needle transseptal crossing device in atrial fibrillation cryoballoon ablation procedures.

INTRODUCTION: In cryoballoon ablation (CBA) procedures, transseptal access (TSA) is generally achieved using a standard sheath and needle system that is exchanged for the cryoballoon delivery sheath and dilator over a long wire. Sheath exchange has been related with air embolic events. Recently, an integrated dilator-needle system assembled to the cryoballoon sheath was introduced. We aimed to evaluate the efficacy and safety of an integrated TSA tool compared with the traditional approach in atrial fibrillation CBA procedures. METHODS: Patients scheduled for CBA procedures were randomized 1:1 to traditional TSA (t-TSA) or integrated TSA (i-TSA). TSA time was defined as time from superior vena cava to LA insertion of the cryoballoon delivery sheath, after sheath exchange (t-TSA) or directly (i-TSA). RESULTS: Ninety-seven patients (76 males, mean age 59 ± 10 years) were randomized, 48 patients underwent t-TSA, and 49 i-TSA. Mean TSA time was 5 min 59 s ± 5 min 36 s in the t-TSA group and 2 min 59 s ± 2 min 14 s in the i-TSA group (p < .001). Total fluoroscopy time, skin-to-skin procedure time, and LA dwell time were respectively 15 ± 6, 69 ± 16, and 44 ± 12 min in the t-TSA group and 13 ± 6, 65 ± 15, and 43 ± 11 min in the i-TSA group (p = ns). No clinically significant acute complications related to TSA were noted in both cohorts. CONCLUSION: This is the first randomized study comparing both TSA approaches. TSA in CBA procedures using this integrated tool enables a safe and efficient workflow, reducing TSA time and avoiding sheath exchange.

Association between proactive esophageal cooling and increased lab throughput.

INTRODUCTION: Proactive esophageal cooling has been FDA cleared to reduce the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures. Data suggest that procedure times for RF pulmonary vein isolation (PVI) also decrease when proactive esophageal cooling is employed instead of luminal esophageal temperature (LET) monitoring. Reduced procedure times may allow increased electrophysiology (EP) lab throughput. We aimed to quantify the change in EP lab throughput of PVI cases after the introduction of proactive esophageal cooling. METHODS: EP lab throughput data were obtained from three EP groups. We then compared EP lab throughput over equal time frames at each site before (pre-adoption) and after (post-adoption) the adoption of proactive esophageal cooling. RESULTS: Over the time frame of the study, a total of 2498 PVIs were performed over a combined 74 months, with cooling adopted in September 2021, November 2021, and March 2022 at each respective site. In the pre-adoption time frame, 1026 PVIs were performed using a combination of LET monitoring with the addition of esophageal deviation when deemed necessary by the operator. In the post-adoption time frame, 1472 PVIs were performed using exclusively proactive esophageal cooling, representing a mean 43% increase in throughput (p < .0001), despite the loss of two operators during the post-adoption time frame. CONCLUSION: Adoption of proactive esophageal cooling during PVI ablation procedures is associated with a significant increase in EP lab throughput, even after a reduction in total number of operating physicians in the post-adoption group.

P-wave alternans rebound following pulmonary vein isolation predicts atrial arrhythmia recurrence.

INTRODUCTION: Numerous P-wave indices have been explored as biomarkers to assess atrial fibrillation (AF) risk and the impact of therapy with variable success. OBJECTIVE: We investigated the utility of P-wave alternans (PWA) to track the effects of pulmonary vein isolation (PVI) and to predict atrial arrhythmia recurrence. METHODS: This medical records study included patients who underwent PVI for AF ablation at our institution, along with 20 control subjects without AF or overt cardiovascular disease. PWA was assessed using novel artificial intelligence-enabled modified moving average (AI-MMA) algorithms. PWA was monitored from the 12-lead ECG at ~1 h before and ~16 h after PVI (n = 45) and at the 4- to 17-week clinically indicated follow-up visit (n = 30). The arrhythmia follow-up period was 955 ± 112 days. RESULTS: PVI acutely reduced PWA by 48%-63% (p < .05) to control ranges in leads II, III, aVF, the leads with the greatest sensitivity in monitoring PWA. Pre-ablation PWA was ~6 µV and decreased to ~3 µV following ablation. Patients who exhibited a rebound in PWA to pre-ablation levels at 4- to 17-week follow-up (p < .01) experienced recurrent atrial arrhythmias, whereas patients whose PWA remained reduced (p = .85) did not, resulting in a significant difference (p < .001) at follow-up. The AUC for PWA's prediction of first recurrence of atrial arrhythmia was 0.81 (p < .01) with 88% sensitivity and 82% specificity. Kaplan-Meier analysis estimated atrial arrhythmia-free survival (p < .01) with an adjusted hazard ratio of 3.4 (95% CI: 1.47-5.24, p < .02). CONCLUSION: A rebound in PWA to pre-ablation levels detected by AI-MMA in the 12-lead ECG at standard clinical follow-up predicts atrial arrhythmia recurrence.

Cryoablation of atrial fibrillation in "very severe" obese patients (BMI ≥ 40): Indications, feasibility, procedural safety and efficacy, and clinical outcome (the ICE-Obese Extreme).

BACKGROUND: Management of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited. METHODS: Highly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body-weight-reduction underwent CBA. RESULTS: Data of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch-up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real-time-isolation (78.6% vs. 78.5%), single-shot-isolation (86.5% vs. 88.8%), but significantly longer time-to-sustained-isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture-site-complication (6.9% vs. 1.6%) in Group A. One-year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p < .001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p = .889). In Re-Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p = .089). CONCLUSION: For very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome.

Effect of early cryoballoon ablation on atrial fibrillation recurrence-A Danish nationwide register study.

INTRODUCTION: Cryoballoon ablation is a safe and efficient rhythm control strategy in atrial fibrillation (AF) patients. The impact of time from diagnosis to ablation is unclear. The aim of this study was to examine the impact of timing of first-time cryoballoon ablation on AF recurrence in a nationwide cohort of AF patients. METHODS AND RESULTS: From nationwide registers, all AF patients ≥18 years of age who underwent first-time AF cryoballoon ablation in Denmark from 2012 to 2018 were included. The AF patients were stratified by ablation timing: Early group (≤1 year after AF diagnosis), intermediate group (1-3 years after AF diagnosis), and late group (≥3 years after AF diagnosis). By adjusted Cox regression models, the effect of timing on AF recurrence was examined. This study included 1064 AF patients with a median age of 63 years. Most patients were male (66%) and had paroxysmal AF (67%). The 1-year risk of AF recurrence increased from 31% in the early group to 41% and 44% in the intermediate and late group. The hazard ratios (95% confidence intervals) were 1.28 (0.95, 1.74) in the intermediate group and 1.42 (1.09, 1.86) in the late group when compared to the early group. Continuous diagnosis-to-ablation time seemed to have the greatest impact on AF recurrence within the first 2 years. CONCLUSION: In AF patients undergoing cryoballoon ablation, late timing of ablation was associated with a significantly higher AF recurrence rate when compared to early timing of ablation. These findings support early cryoballoon ablation to improve the outcomes after ablation.

Vein of Marshall chemical ablation decreases atrial fibrillation drivers detected by CARTOFINDER.

INTRODUCTION: This study sought to elucidate the impact of vein of Marshall (VOM) chemical ablation on atrial fibrillation (AF) drivers by investigating the changes in CARTOFINDER mappings before and after VOM chemical ablation in patients with persistent AF. METHODS: This study included 23 consecutive patients undergoing catheter ablation for long-persistent AF (>18 months). VOM chemical ablation was performed following pulmonary vein isolation. CARTOFINDER and AF cycle length (AFCL) maps were created in the left atrium (LA) before and after VOM chemical ablation. The LA was divided into 8 segments, and the number of focal activation points with 6 or more repetitions was counted in each segment. RESULTS: The number of focal activation points was largest in the LA appendage (LAA). After VOM chemical ablation, the number of focal activation points in the LA decreased significantly (37 [interquartile range, IQR: 19-55] vs. 15 [IQR: 7-21], p < .001), and median AFCL was significantly prolonged (159 [147-168] vs. 164 [150-173] ms, p < .001). In the assessment of each segment, significant decreases in focal activation points were observed in the inferior, lateral, and anterior segments and LAA. Among the focal activation points disappearing after chemical ablation, the number in the non-ethanol-affected area was significantly larger than that in the affected area (13 [8-25] vs. 4 [1-10], p < .001). CONCLUSIONS: VOM chemical ablation decreases AF drivers detected by CARTOFINDER. Mechanisms other than direct myocardial damage are considered to contribute the attenuation of AF drivers.

Step-by-step recommendations utilizing four-dimensional intracardiac echocardiography in left atrial appendage procedures.

INTRODUCTION: Four-dimensional (4D) intracardiac echocardiography (ICE) is a novel cardiac imaging modality that has been applied to various workflows, including catheter ablation, tricuspid valve repair, and left atrial appendage occlusion (LAAO). The use of this type of advanced ICE imaging may ultimately allow for the replacement of transesophageal echocardiography (TEE) for LAAO, providing comparable imaging quality while eliminating the need for general anesthesia. METHODS: Based on our initial clinical experience with 4D ICE in LAAO, we have developed an optimized workflow for the use of the NUVISION™ 4D ICE Catheter in conjunction with the GE E95 and S70N Ultrasound Systems in LAAO. In this manuscript, we provide a step-by-step guide to using 4D ICE in conjunction with compatible imaging consoles. We have also evaluated the performance of 4D ICE with the NUVISION Ultrasound Catheter versus TEE in one LAAO case and present those results here. RESULTS: In our comparison of 4D ICE using our optimized workflow with TEE in an LAAO case, ICE LAA measurements were similar to those from TEE. The best image resolution was seen via ICE in 2-dimensional and multislice modes (triplane and biplane). The FlexiSlice multiplanar reconstruction tool, which creates an en-face image derived from a 4D volume set, also provided valuable information but yielded slightly lower image quality, as expected for these volume-derived images. For this case, comparable images were obtained with TEE and ICE but with less need to reposition the ICE catheter. CONCLUSION: The use of optimized 4D ICE catheter workflow recommendations allows for efficient LAAO procedures, with higher resolution imaging, comparable to TEE.

Real-world evidence demonstrates an appropriate atrial fibrillation population for hybrid convergent approach versus stand-alone cryoballoon ablation: A long-term safety and efficacy study.

INTRODUCTION: A hybrid convergent approach (endocardial and epicardial ablation) demonstrated superior effectiveness in a recent randomized study for long-standing persistent atrial fibrillation (LSPAF). Yet, there is a lack of real-world, long-term evidence as to which patients are best candidates for a hybrid convergent approach compared to standard endocardial cryoballoon pulmonary vein isolation (CB PVI). METHODS AND RESULTS: This single-center, retrospective analysis spanning from 2010 to 2015 compared two distinctly different atrial fibrillation (AF) cohorts; one treated with stand-alone cryoablation and one treated with a hybrid convergent approach. Baseline characteristics described candidates for each approach. The following criteria were utilized to determine CB PVI candidacy: (1) paroxysmal AF (PAF) (stage 3A) with failed class I/III antiarrhythmic drug (AAD) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD unwilling to undergo hybrid procedure. Selection criteria for the hybrid procedure included: (1) PAF refractory to both class I/III AAD and prior CB PVI (stage 3D) or (2) persistent/LSPAF (stage 3B/3C/3D) with failed class I/III AAD agreeable to hybrid procedure. Prior sternotomy was excluded. Serial electrocardiograms and continuous monitoring evaluated primary efficacy outcome of time-to-first recurrence of atrial arrhythmia after a 90-day blanking period. Secondary outcomes were procedure-related complications and AAD use (at discharge, 12, and 36 months). Kaplan-Meier methods evaluated arrhythmia recurrence. Of 276 patients, 197 (64.2 ± 10.6 years old; 66.5% male; 74.1% 3A-PAF; 18.3% 3B/3D-persistent AF; 1.0% 3C-LSPAF; 6.6% undetermined) underwent CB PVI and 79 (61.4 ± 8.1 years old; 83.5% male; 41.8% 3D-PAF; 45.5% 3B/3D-persistent AF; 12.7% 3C/3D-LSPAF) underwent hybrid procedure. Arrhythmia freedom through 36 months was 55.2% for CB PVI and 50.4% for hybrid (p = .32). Class I AAD utilization at discharge occurred in 38 (19.3%) patients in the CB PVI group and 5 (6.3%) patients in the hybrid group (p = .01). CB PVI class I AAD utilization at 12 months occurred in 14 (9.0) patients versus 0 patients for hybrid convergent (p = .004). Patients with one or more adverse event were as follows: two (1.0%) in the CB PVI group (both transient phrenic nerve palsy) and three (3.7%) in the hybrid group (two with significant bleeding and one with wound infection) (p = .14). CONCLUSION: This study demonstrated that patients with more complex forms of AF (3D-PAF or 3B/3C/3D-persistent/LSPAF) could be well managed with a convergent approach. In a real-world evaluation, outcomes match safety and efficacy thresholds achieved for patients with earlier, less complex AF etiologies treated by CB PVI alone.

Determinants of left atrial local impedance: Relationships with contact force, atrial fibrosis, and rhythm.

INTRODUCTION: The relationships between baseline tissue local impedance (LI), contact force (CF), atrial fibrosis, and atrial rhythm are uninvestigated in a clinical setting. We compared the relationship of LI and CF between atrial fibrillation (AF) and sinus rhythm (SR) accounting for the effects of atrial fibrosis as assessed by bipolar voltage and LI. METHODS: Patients undergoing persistent AF ablation were recruited. LI was recorded referenced to patient blood pool (LIr) and concurrent to changes in CF, with data collected at the same locations in AF and SR. RESULTS: Twenty patients were recruited. 109 locations were sampled obtaining 1903 data points (SR: 966, AF: 937). CF correlated strongly with LI (repeated measures correlation = 0.64). The relationship between CF and LIr was logarithmic. Rhythm and CF had a significant main (both p < .0005) and interaction effect (p = .022) on tissue LI: AF demonstrated higher LIr values than SR for similar CF. Bipolar voltage had no effect on the relationship of CF to LIr in either rhythm. Assessing fibrosis using LIr showed an interaction effect with CF for LIr in SR and AF, (SR: p < .0005, AF: p = .01), with increased fibrosis showing lesser change in LIr per gram of CF. CONCLUSIONS: CF and rhythm significantly affect the measured LIr of LA myocardium. Optimal catheter-tissue coupling may be better achieved with higher levels of CF and in AF rather than SR. Atrial fibrosis, as assessed by LIr but not bipolar voltage, affected the CF-LI relationship.

Lesion metrics and 12-month outcomes of very-high power short duration radiofrequency ablation (90W/4 s) under mild conscious sedation.

INTRODUCTION: Pulmonary vein isolation (PVI) is often performed under general anaesthesia (GA) or deep sedation. Anaesthetic availability is limited in many centers, and deep sedation is prohibited in some countries without anaesthetic support. Very high-power short duration (vHPSD-90W/4 s) PVI using the Q-Dot catheter is generally well tolerated under mild conscious sedation (MCS) though an understanding of catheter stability and long-term effectiveness is lacking. We analyzed lesion metrics and 12-month freedom from atrial arrythmia with this approach. METHODS: Our approach to radiofrequency (RF) PVI under MCS is standardized and includes a single catheter approach with a steerable sheath. We identified patients undergoing Q-Dot RF PVI between March 2021 and December 2022 in our center, comparing those undergoing vHPSD ablation under MCS (90W/MCS) against those undergoing 50 W ablation under GA (50 W/GA) up to 12 months of follow-up. Data were extracted from clinical records and the CARTO system. RESULTS: Eighty-three patients met our inclusion criteria (51 90W/MCS; 32 50 W/GA). Despite shorter ablation times (353 vs. 886 s; p < .001), the 90 W/MCS group received more lesions (median 87 vs. 58, p < .001), resulting in similar procedure times (149.3 vs. 149.1 min; p = .981). PVI was achieved in all cases, and first pass isolation rates were similar (left wide antral circumferential ablation [WACA] 82.4% vs. 87.5%, p = .758; right WACA 74.5% vs. 78.1%, p = .796; 90 W/MCS vs. 50 W/GA respectively). Analysis of 6647 ablation lesions found similar mean impedance drops (10.0 ± 1.9 Ω vs. 10.0 ± 2.2 Ω; p = .989) and mean contact force (14.6 ± 2.0 g vs. 15.1 ± 1.6 g; p = .248). Only median 2.5% of lesions in the 90 W/MCS cohort failed to achieve ≥ 5 Ω drop. In the 90 W/MCS group, there were no procedural related complications, and 12-month freedom from atrial arrhythmia was observed in 78.4%. CONCLUSION: vHPSD PVI is feasible under MCS, with encouraging acute and long-term procedural outcomes. This provides a compelling option for centers with limited anaesthetic support.