Catheter ablation for persistent atrial fibrillation: patterns of recurrence and impact on quality of life and health care utilisation.

BACKGROUND AND AIMS: Patterns of atrial fibrillation (AF) recurrence post catheter ablation for persistent AF are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for persistent AF (PsAF) and the implications for healthcare utilisation and quality of life. METHODS: This was a post-hoc analysis of the CAPLA study, an international, multi-centre study that randomised patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring. RESULTS: 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomisation groups (p=0.508). Median AF burden was 27.4% in PsAF recurrence and 0.9% in paroxysmal AF (PAF) recurrence (p<0.001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs PAF 60%, p<0.001) and larger left atrial volume (PsAF 54.2±19.3 ml/m² vs PAF 44.8±11.6 ml/m², p=0.008). Healthcare utilisation was significantly higher in PsAF (45 patients [78.9%]) vs PAF recurrence (45 patients [46.4%], p<0.001) and lowest in those without recurrence (17 patients [9.5%], p<0.001). Patients without AF recurrence had greater improvements in quality of life as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3±25.2 points) compared to those with PAF (Δ24.0±25.0 points, p=0.012) or PsAF (Δ13.4±22.9 points, p<0.001) recurrence. CONCLUSIONS: AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilisation and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF.

Initial clinical experience with the balloon-in-basket pulsed field ablation system: acute results of the VOLT CE mark feasibility study.

AIMS: Pulsed field ablation (PFA) for the treatment of atrial fibrillation (AF) potentially offers improved safety and procedural efficiencies compared with thermal ablation. Opportunities remain to improve effective circumferential lesion delivery, safety, and workflow of first-generation PFA systems. In this study, we aim to evaluate the initial clinical experience with a balloon-in-basket, 3D integrated PFA system with a purpose-built form factor for pulmonary vein (PV) isolation. METHODS AND RESULTS: The VOLT CE Mark Study is a pre-market, prospective, multi-centre, single-arm study to evaluate the safety and effectiveness of the Volt™ PFA system for the treatment of paroxysmal (PAF) or persistent AF (PersAF). Feasibility sub-study subjects underwent phrenic nerve evaluation, endoscopy, chest computed tomography, and cerebral magnetic resonance imaging. Study endpoints were the rate of primary serious adverse event within 7 days and acute procedural effectiveness. A total of 32 subjects (age 61.6 ± 9.6 years, 65.6% male, 84.4% PAF) were enrolled and treated in the feasibility sub-study and completed a 30-day follow-up. Acute effectiveness was achieved in 99.2% (127/128) of treated PVs (96.9% of subjects, 31/32) with 23.8 ± 4.2 PFA applications/subject. Procedure, fluoroscopy, LA dwell, and transpired ablation times were 124.6 ± 28.1, 19.8 ± 8.9, 53.0 ± 21.0, and 48.0 ± 19.9 min, respectively. Systematic assessments of initial safety revealed no phrenic nerve injury, pulmonary vein stenosis, or oesophageal lesions causally related to the PFA system and three subjects with silent cerebral lesions (9.4%). There were no primary serious adverse events. CONCLUSION: The initial clinical use of the Volt PFA System demonstrates acute safety and effectiveness in the treatment of symptomatic, drug refractory AF.

Impact of Posterior Wall Isolation During AF Ablation on the Incidence of Left Atrial Flutter.

BACKGROUND: Linear and complex electrogram ablation (LCEA) beyond pulmonary vein isolation (PVI) is associated with an increase in left atrial macro-re-entrant tachycardias (LAMTs). Posterior wall isolation (PWI) is increasingly performed to improve AF ablation outcomes. However, the impact of PWI on the incidence of LAMT is unknown. OBJECTIVES: The purpose of this study was to establish the incidence of LAMT following PVI alone vs PVI + PWI vs PVI + PWI + LCEA. METHODS: Consecutive patients undergoing catheter ablation for AF or LAMT post-AF ablation between 2008 and 2022 from 4 electrophysiology centers were reviewed with a minimum follow-up of 12 months. RESULTS: In total, 5,619 (4,419 index, 1,100 redo) AF ablation procedures were performed in 4,783 patients (mean age 60.9 ± 10.6 years, 70.7% men). Over a mean follow-up of 6.4 ± 3.8 years, 246 procedures for LAMT were performed in 214 patients at a mean of 2.6 ± 0.6 years post-AF ablation. Perimitral (52.8% of patients), roof-dependent (27.1%), PV gap-related (17.3%), and anterior circuits (8.9%) were most common, with 16.4% demonstrating multiple circuits. The incidence of LAMT was significantly higher following PVI + PWI (6.2%) vs PVI alone (3.0%; P < 0.0001) and following PVI + PWI + LCEA vs PVI + PWI (12.5%; P = 0.019). Conduction gaps in previous ablation lines were responsible for LAMT in 28.4% post-PVI alone, 35.3% post-PVI + PWI (P = 0.386), and 81.8% post-PVI + PWI + LCEA (P < 0.005). CONCLUSIONS: The incidence of LAMT following PVI + PWI is higher than with PVI alone but significantly lower than with more extensive atrial substrate modification. Given a low frequency of LAMT following PWI, empiric mitral isthmus ablation is not justified and may be proarrhythmic.

Pulmonary Veins Function as Echo Chambers in Persistent Atrial Fibrillation: Circuitous Re-Entry Generates Outgoing Wavefronts.

BACKGROUND: Although the substrate in persistent atrial fibrillation (PeAF) is not limited to the pulmonary veins (PVs), PV isolation (PVI) remains the cornerstone ablation strategy. OBJECTIVES: The aim of this study was to describe the mechanism of outgoing wavefronts (WFs) originating in the PV sleeves during PeAF. METHODS: Eleven patients presenting for first-time PeAF ablation were recruited (mean age 63.1 ± 10.9 years, 91% men). A 64-electrode catheter (Constellation; 38 mm) was positioned within the PV under fluoroscopic guidance. An inverse mapping technique was used to reconstruct unipolar atrial electrograms on the PV surface, and the resulting phase maps were used to identify incoming and outgoing WFs at the PV junction and to classify focal and re-entrant activity within the PV sleeves. RESULTS: During PeAF, the PVs gave rise to outgoing WFs with a frequency of 3.7 s-1 (Q1-Q3: 3.4-5.4 s-1) compared with 3.6 s-1 (Q1-Q3: 2.8-4.2 s-1) for incoming WFs. Circuitous macroscopic re-entry was the dominant mechanism driving outgoing WFs (frequency of re-entry 2.7 s-1 [Q1-Q3: 2.0-3.3 s-1] compared with focal activity 1.4 s-1 [Q1-Q3: 1.1-1.5 s-1]; P < 0.006). This was initiated by incoming WFs in 80% of cases. Consecutive focal activation from the same location was infrequent (10.0% ± 6.6%, n = 10). Rotors ≥360° were never observed. The median ratio (R) of outgoing to incoming WF frequency was 1.14 (Q1-Q3: 0.84-1.75), with R > 1 in 6 of 11 PVs. CONCLUSIONS: Electric activity generated by PV sleeves during PeAF is due mainly to circuitous re-entry initiated by incoming waves, frequently with R > 1. That is, the PVs act less as drivers of atrial fibrillation than as "echo chambers" that sustain and amplify fibrillatory activity.

2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

Sex-specific outcomes after catheter ablation for persistent AF.

BACKGROUND: Sex-specific outcomes after catheter ablation (CA) for atrial fibrillation (AF) have reported conflicting findings. OBJECTIVE: We examined the impact of female sex on outcomes in patients with persistent AF (PsAF) from the Catheter Ablation for Persistent Atrial Fibrillation: A Multicentre Randomized Trial of Pulmonary Vein Isolation vs PVI with Posterior Left Atrial Wall Isolation (CAPLA) randomized trial. METHODS: A total of 338 patients with PsAF were randomized to pulmonary vein isolation (PVI) or PVI with posterior wall isolation (PWI). The primary outcome was arrhythmia recurrence at 12 months. Clinical and electroanatomical characteristics, arrhythmia recurrence, and quality of life were compared between women and men. RESULTS: Seventy-nine women (23.4%; PVI 37; PVI + PWI 42) and 259 men (76.6%; PVI 131; PVI + PWI 128) underwent AF ablation. Women were older {median age 70.4 (interquartile range [IQR] 64.8-74.6) years vs 64.0 (IQR 56.7-69.7) years; P < .001} and had more advanced left atrial electroanatomical remodeling. At 12 months, arrhythmia-free survival was lower in women (44.3% vs 56.8% in men; hazard ratio 1.44; 95% confidence interval 1.02-2.04; log-rank, P = .036). PWI did not improve arrhythmia-free survival at 12 months (hazard ratio 1.02; 95% confidence interval 0.74-1.40; log-rank, P = .711). The median AF burden was 0% in both groups (women: IQR 0.0%-2.2% vs men: IQR 0.0%-2.8%; P = .804). Health care utilization was comparable between women (36.7%) and men (30.1%) (P = .241); however, women were more likely to undergo a repeat procedure (17.7% vs 6.9%; P = .007). Women reported more severe baseline anxiety (average Hospital Anxiety and Depression Scale [HADS] anxiety score 7.5 ± 4.9 vs 6.3 ± 4.3 in men; P = .035) and AF-related symptoms (baseline Atrial Fibrillation Effect on Quality-of-Life Questionnaire [AFEQT] score 46.7 ± 20.7 vs 55.9 ± 23.0 in men; P = .002), with comparable improvements in psychological symptoms (change in HADS anxiety score -3.8 ± 4.6 vs -3.0 ± 4.5; P = .152 (change in HADS depression score -2.9 ± 5.0 vs -2.6 ± 4.0; P = .542) and greater improvement in AFEQT score compared with men at 12 months (change in AFEQT score +45.9 ± 23.1 vs +39.2 ± 24.8; P = .048). CONCLUSION: Women undergoing CA for PsAF report more significant symptoms and poorer quality of life at baseline than men. Despite higher arrhythmia recurrence and repeat procedures in women, the AF burden was comparably low, resulting in significant improvements in quality of life and psychological well-being after CA in both sexes.

P-Wave Morphology From Common Nonpulmonary Vein Trigger Sites Following Pulmonary Vein and Posterior Wall Isolation.

BACKGROUND: Non-pulmonary vein (PV) triggers are increasingly targeted during atrial fibrillation (AF) ablation. P-wave morphology (PWM) can be useful because point mapping of AF triggers is challenging. The impact of prior ablation on PWM is yet to be determined. OBJECTIVES: This study sought to report PWM before and after left atrial (LA) ablation and construct a P-wave algorithm of common non-PV trigger locations. METHODS: This multicenter, prospective, observational study analyzed the paced PWM of 30 patients with persistent AF undergoing pulmonary vein isolation (PVI) and posterior wall isolation (PWI). Pace mapping was performed at the SVC, crista terminalis, inferior tricuspid annulus, coronary sinus ostium, left septum, left atrial appendage, Ligament of Marshall, and inferoposterior LA. The PWM was reported before PVI, then blinded comparisons were made post-PVI and post-PVI + PWI. A P-wave algorithm was constructed. RESULTS: A total of 8,352 paced P waves were prospectively recorded. No significant changes in the PWM were seen post-PVI alone in 2,775 of 2,784 (99.7%) and post-PWI in 2,715 of 2,784 (97.5%). Changes in PWM were predominantly at the IPLA (53 P waves) with a positive P-wave in leads V2 to V6 before biphasic post-PWI, LA appendage (9 P waves), coronary sinus ostium (6 P waves), and ligament of Marshall (3 P waves). A PWM algorithm was created before PVI and accurately predicted the location in 93% post-PVI + PWI. CONCLUSIONS: Minimal change was observed in PWM post-PV and PWI aside from the IPLA location. A P-wave algorithm created before and applied after PVI + PWI provided an accuracy of 93%. PWM provides a reliable tool to guide the localization of common non-PV trigger sites even after PV and PWI.

Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

Serotonin antidepressants and atrial fibrillation burden from cardiac implantable electronic devices.

Objective: Depression and anxiety show a bidirectional relationship with atrial fibrillation (AF). Antidepressant use is associated with a reduction in the incidence of AF. However, no studies have examined the relationship between antidepressant use and AF burden (time in AF). This retrospective cohort study examined cardiac implantable device-detected AF episodes and their relationship with antidepressant use, among other treatment factors. Methods: Consecutive patients from the Western Health Cardiology Department attending pacemaker checks between 2015 and 2021 were included. Patients with permanent AF were excluded, yielding 285 patients with no or paroxysmal AF, with a total of 772 patient encounters. Generalized estimating equations were used to model two processes: binary AF (present/absent) and the number of days in AF for patients with AF. Results: Each yearly increase with age was associated with an increase in the odds of developing AF (OR 1.03 [1.00-1.05], p = .027). Male gender conferred a reduction in AF incidence (OR 0.30 [0.13-0.68], p = .004). Digoxin use was associated with incident AF (OR 4.43 [1.07-18.4], p = .04). Sotalol and heart-failure beta blocker use were associated with a decrease in AF burden (IRR 0.30 [0.12-0.78], p = .013 and 0.33 [0.14-0.81], p = .015). Selective serotonin reuptake inhibitor antidepressant use was associated with reduced AF burden (IRR 0.27 [0.09-0.81], p = .019), as was selective serotonin/noradrenaline reuptake inhibitor use (IRR 0.07 [0.03-0.15], p < .001). Conclusions: Older age, female gender and digoxin are associated with a higher odds of developing incident AF. Sotalol, heart failure beta blockers and serotonin-based antidepressants are associated with reduced AF burden. Further prospective study into the effects of antidepressants on atrial arrhythmias is warranted.

Statement from the Asia Summit: Current state of arrhythmia care in Asia.

On May 27, 2022, the Asia Pacific Heart Rhythm Society and the Heart Rhythm Society convened a meeting of leaders from different professional societies of healthcare providers committed to arrhythmia care from the Asia Pacific region. The overriding goals of the meeting were to discuss clinical and health policy issues that face each country for providing care for patients with electrophysiologic issues, share experiences and best practices, and discuss potential future solutions. Participants were asked to address a series of questions in preparation for the meeting. The format of the meeting was a series of individual country reports presented by the leaders from each of the professional societies followed by open discussion. The recorded presentations from the Asia Summit can be accessed at https://www.heartrhythm365.org/URL/asiasummit-22. Three major themes arose from the discussion. First, the major clinical problems faced by different countries vary. Although atrial fibrillation is common throughout the region, the most important issues also include more general issues such as hypertension, rheumatic heart disease, tobacco abuse, and management of potentially life-threatening problems such as sudden cardiac arrest or profound bradycardia. Second, there is significant variability in the access to advanced arrhythmia care throughout the region due to differences in workforce availability, resources, drug availability, and national health policies. Third, collaboration in the area already occurs between individual countries, but no systematic regional method for working together is present.

Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.

Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients. The aim of this investigation was to determine whether transmural conduction gradients are modified in a rat model of pericardial adiposity. Adult Sprague-Dawley rats were fed control/high-fat diets for 15 wk. Left ventricular 300 µm tangential slices were generated from the endocardium to the epicardium, and conduction was mapped using microelectrode arrays. Slices were then histologically processed to assess fibrosis and cardiomyocyte lipid status. Conduction velocity was significantly greater in epicardial versus endocardial slices in control rats, supporting the concept of a transmural conduction gradient. High-fat diet feeding increased pericardial adiposity and abolished the transmural conduction gradient. Slowed epicardial conduction in epicardial slices strongly correlated with an increase in cardiomyocyte lipid content, but not fibrosis. The positive transmural conduction gradient reported here represents a physiological property of the ventricular activation sequence that likely protects against reentry. The absence of this gradient, secondary to conduction slowing and cardiomyocyte lipid accumulation, specifically in the epicardium, indicates a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.

The Role of Posterior Wall Isolation in Catheter Ablation for Persistent Atrial Fibrillation and Systolic Heart Failure: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Catheter ablation for patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) is associated with improved left ventricular ejection fraction (LVEF) and survival compared with medical therapy. Nonrandomized studies have reported improved success with posterior wall isolation (PWI). Objective: To determine the impact of pulmonary vein isolation (PVI) with PWI vs PVI alone on outcomes in patients with HFrEF. Design, Setting, and Participants: This was an ad hoc secondary analysis of the CAPLA trial, a multicenter, prospective, randomized control trial that involved 11 centers in 3 countries (Australia, Canada, and UK). CAPLA featured 338 patients with persistent AF randomized to either PVI plusPWI or PVI alone. This substudy included patients in the original CAPLA study who had symptomatic HFrEF (LVEF <50% and New York Heart Association class ≥II). Interventions: Pulmonary vein isolation with PWI vs PVI alone. Main Outcomes and Measures: The primary end point was freedom from any documented atrial arrhythmia greater than 30 seconds, after a single ablation procedure, without the use of antiarrhythmic drug (AAD) therapy at 12 months. Results: A total of 98 patients with persistent AF and symptomatic HFrEF were identified (mean [SD] age, 62.1 [9.8] years; 79.5% men; and mean [SD] LVEF at baseline, 34.6% [7.9%]). After 12 months, 58.7% of patients with PVI plus PWI were free from recurrent atrial arrhythmia without the use of AAD therapy vs 61.5% with PVI alone (hazard ratio, 1.02; 95% CI, 0.54-1.91; P = .96). There were no significant differences in freedom from atrial arrhythmia with or without AAD therapy after multiple procedures (PVI plus PWI vs PVI alone, 60.9% vs 65.4%; P = .73) or AF burden (median, 0% in both groups; P = .78). Mean LVEF improved substantially in PVI plus PWI (∆ LVEF, 19.3% [13.0%; P < .01) and PVI alone (18.2% [14.1%; P < .01), with no difference between groups (P = .71). Normalization of LV function occurred in 65.2% of patients in the PVI plus PWI group and 50.0% of patients with PVI alone (P = .13). Conclusions and Relevance: The results of this study indicate that addition of PWI to PVI did not improve freedom from arrhythmia recurrence or recovery of LVEF in patients with persistent AF and symptomatic HFrEF. Catheter ablation was associated with significant improvements in systolic function, irrespective of ablation strategy used. These results caution against the routine inclusion of PWI in patients with HFrEF undergoing first-time catheter ablation for persistent AF. Trial Registration: http://anzctr.org.au Identifier: ACTRN12616001436460.

The impact of age on ablation outcomes in AF-mediated cardiomyopathy.

INTRODUCTION: The absence of ventricular scar in patients with atrial fibrillation (AF) and systolic heart failure (HF) predicts left ventricular (LV) recovery following AF ablation. It is unknown whether age impacts the degree of LV recovery, reverse remodeling, or AF recurrence following catheter ablation (CA) among this population. OBJECTIVES: To evaluate the impact of age on LV recovery and AF recurrence in a population with AF and systolic HF without fibrosis (termed AF-mediated cardiomyopathy) following CA. METHODS: Consecutive patients undergoing CA between 2013 and 2021 with LV ejection fraction (LVEF) < 45% and absence of cardiac magnetic resonance imaging (CMR) detected LV myocardial fibrosis were stratified by age (<65 vs. ≥65 years). Following CA, participants underwent remote rhythm monitoring for 12 months with repeat CMR for HF surveillance. RESULTS: The study population consisted of 70 patients (10% female, mean LVEF 33 ± 9%), stratified into younger (age < 65 years, 63%) and older (age ≥ 65 years, 37%) cohorts. Baseline comorbidities, LVEF (34 ± 9 vs. 33 ± 8 ≥65 years, p = .686), atrial and ventricular dimensions (left atrial volume index: 55 ± 21 vs. 56 ± 14 mL/m2 age ≥ 65, p = .834; indexed left ventricular end-diastolic volume: 108 ± 40 vs. 104 ± 28 mL/m2 age ≥ 65, p = .681), pharmacotherapy and ablation strategy (pulmonary vein isolation in all; posterior wall isolation in 27% vs. 19% age ≥ 65, p = .448; cavotricuspid isthmus in 9% vs. 11.5% age ≥ 65) were comparable (all p > .05) albeit a higher CHADS2 VASc score in the older cohort (2.7 ± 0.9 vs. 1.6 ± 0.6 age < 65, p < .001).   Freedom from AF was comparable (hazard ratio: 0.65, 95% confidence interval: 0.38-1.48, LogRank p = .283) as was AF burden [0% (interquartile range, IQR: 0.0-2.1) vs. age ≥ 65: [0% (IQR 0.0-1.7), p = .516], irrespective of age. There was a significant improvement in LV systolic function in both groups (ΔLVEF + 21 ± 14% vs. +21 ± 12% age ≥ 65, p = .913), with LV recovery in the vast majority (73% vs. 69%, respectively, p = .759) at 13 (IQR: 12-16) months. This was accompanied by comparable improvements in functional status (New York Heart Association class p = .851; 6-min walk distance 50 ± 61 vs. 93 ± 134 m in age ≥ 65, p = .066), biomarkers (ΔN-terminal-pro brain natriuretic peptide -139 ± 246 vs. -168 ± 181 age ≥ 65,p = .629) and HF symptoms (Short Form-36 survey Δphysical component summary p = .483/Δmental component summary, p = .841). CONCLUSION: In patients undergoing CA for AF with systolic HF in the absence of ventricular scar, comparable improvements in ventricular function, symptoms, and freedom from AF are achieved irrespective of age.

Impact of Posterior Left Atrial Voltage on Ablation Outcomes in Persistent Atrial Fibrillation: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in patients with persistent atrial fibrillation (PsAF). Adjunctive ablation targeting low voltage areas (LVAs) may improve arrhythmia outcomes. OBJECTIVES: This study aims to compare the outcomes of adding posterior wall isolation (PWI) to PVI, vs PVI alone in PsAF patients with posterior wall LVAs. METHODS: The CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) study was a multicenter, randomized trial involving PsAF patients randomized 1:1 to either PVI alone or PVI with PWI. Voltage mapping performed during pacing pre-ablation was reviewed offline, with LVA defined as bipolar voltage of <0.5 mV. The primary endpoint was freedom from any documented atrial arrhythmia of >30 seconds off antiarrhythmic medication at 12 months after a single ablation procedure in patients with posterior LVA. RESULTS: A total of 210 patients (average 64.6 ± 9.2 years,73.3% males, median atrial fibrillation duration 4.5 months [IQR: 2 to 8 months]) underwent multipolar left atrial mapping during coronary sinus pacing with posterior LVA present in 69 (32.9%). Patients with posterior LVA were more likely to have LVA in other atrial regions (91.7% vs 57.1%; P < 0.01), larger left atrial diameter (4.8 cm vs 4.4 cm; P < 0.01), and significantly increased risk of atrial arrhythmia recurrence at 12 months (LVA: 56.5% vs no LVA: 41.4%; HR: 1.51; 95% CI: 1.01-2.27; P = 0.04) compared to no posterior LVA. However, the addition of PWI to PVI did not significantly improve freedom from atrial arrhythmia recurrence over PVI alone (PVI with PWI: 44.8% vs PVI: 41.9%; HR: 0.95; 95% CI: 0.51-1.79; P = 0.95). CONCLUSIONS: In patients with PsAF undergoing catheter ablation, posterior LVA was associated with a significant increase in atrial arrhythmia recurrence. However, the addition of PWI in those with posterior LVA did not reduce atrial arrhythmia recurrence over PVI alone.

Posterior Wall Isolation Improves Outcomes for Persistent AF With Rapid Posterior Wall Activity: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in persistent atrial fibrillation (PerAF) than in paroxysmal atrial fibrillation (AF). However, the CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA randomized clinical trial) of PVI vs posterior wall isolation (PWI) did not support empiric PWI in PerAF. We examined pulmonary vein (PV) and posterior wall (PW) electrical characteristics to determine if select patients may benefit from additional PWI. OBJECTIVES: This study sought to determine the impact of PV and PW electrical characteristics on AF ablation outcomes in the CAPLA randomized study. METHODS: Participants in spontaneous AF at the time of ablation were included from the CAPLA study. The mean, shortest, and longest PV, PW, and left atrial (LA) appendage cycle length measurements were annotated preablation using a multipolar catheter for 100 consecutive cycles. Next, cardioversion was performed with a high-density LA voltage map completed. Cox proportional hazards regression was utilized to determine clinical and electroanatomic predictors of AF recurrence overall and according to ablation strategy. Follow-up included twice daily single-lead electrocardiograms or continuous monitoring for 12 months. RESULTS: A total of 151 patients (27% female, age 65 ± 9 years, 18% long-standing PerAF, LA volume index 52 ± 16 mL/m2, median AF duration 5 months [IQR: 2-10 months]) were in AF on the day of procedure and were randomized to PVI alone (50%) or PVI+PWI (50%) according to the CAPLA randomized clinical trial protocol. Baseline clinical, echocardiographic, and electroanatomic parameters were comparable between groups (all P > 0.05) including PV and PW characteristics. After 12 months, freedom from AF off antiarrhythmic drug therapy was 51.7% in PVI and 49.7% in PVI+PWI (log-rank P = 0.564). Rapid PW activity was defined as less than the median of the shortest PW cycle length (140 ms) and rapid PV activity was defined as less than the median of the shortest PV cycle length (126 ms). In those with rapid PW activity, the addition of PWI was associated with greater arrhythmia-free survival (56.4%) vs PVI alone (38.6%) (HR: 0.78; 95% CI: 0.67-0.94; log-rank P = 0.030). Moreover, in those undergoing PVI only, the risk of AF recurrence was higher in those with rapid PW activity (55.3% vs 46.5% in slower PW activity; HR: 1.50, 95%CI 1.11-2.26; log-rank P = 0.036). Rapid PV activity and PV cycle length (individual PVs or average of all 4 PVs) were not associated with outcome (all P > 0.05) regardless of ablation strategy. There was no correlation between PW cycle length and posterior low voltage (r = -0.06, P = 0.496). The addition of PWI did not improve arrhythmia-free survival in subgroups with LA enlargement (LA volume index >34 mL/m2) (HR: 0.69; 95% CI: 0.39-1.25; P = 0.301), posterior low-voltage zone (HR: 1.06; 95% CI: 0.68-1.66; P = 0.807), or long-standing PerAF (HR: 1.10; 95% CI: 0.71-1.72; P = 0.669). CONCLUSIONS: Rapid PW activity is associated with an increased risk of AF recurrence post-catheter ablation. The addition of PWI in this subgroup was associated with a significant improvement in freedom from AF compared with PVI alone. The presence of rapid PW activity may identify patients with PerAF likely to benefit from PWI.

Atrial Fibrillation Catheter Ablation vs Medical Therapy and Psychological Distress: A Randomized Clinical Trial.

Importance: The impact of atrial fibrillation (AF) catheter ablation on mental health outcomes is not well understood. Objective: To determine whether AF catheter ablation is associated with greater improvements in markers of psychological distress compared with medical therapy alone. Design, Setting, and Participants: The Randomized Evaluation of the Impact of Catheter Ablation on Psychological Distress in Atrial Fibrillation (REMEDIAL) study was a randomized trial of symptomatic participants conducted in 2 AF centers in Australia between June 2018 and March 2021. Interventions: Participants were randomized to receive AF catheter ablation (n = 52) or medical therapy (n = 48). Main Outcomes and Measures: The primary outcome was Hospital Anxiety and Depression Scale (HADS) score at 12 months. Secondary outcomes included follow-up assessments of prevalence of severe psychological distress (HADS score >15), anxiety HADS score, depression HADS score, and Beck Depression Inventory-II (BDI-II) score. Arrhythmia recurrence and AF burden data were also analyzed. Results: A total of 100 participants were randomized (mean age, 59 [12] years; 31 [32%] women; 54% with paroxysmal AF). Successful pulmonary vein isolation was achieved in all participants in the ablation group. The combined HADS score was lower in the ablation group vs the medical group at 6 months (8.2 [5.4] vs 11.9 [7.2]; P = .006) and at 12 months (7.6 [5.3] vs 11.8 [8.6]; between-group difference, -4.17 [95% CI, -7.04 to -1.31]; P = .005). Similarly, the prevalence of severe psychological distress was lower in the ablation group vs the medical therapy group at 6 months (14.2% vs 34%; P = .02) and at 12 months (10.2% vs 31.9%; P = .01), as was the anxiety HADS score at 6 months (4.7 [3.2] vs 6.4 [3.9]; P = .02) and 12 months (4.5 [3.3] vs 6.6 [4.8]; P = .02); the depression HADS score at 3 months (3.7 [2.6] vs 5.2 [4.0]; P = .047), 6 months (3.4 [2.7] vs 5.5 [3.9]; P = .004), and 12 months (3.1 [2.6] vs 5.2 [3.9]; P = .004); and the BDI-II score at 6 months (7.2 [6.1] vs 11.5 [9.0]; P = .01) and 12 months (6.6 [7.2] vs 10.9 [8.2]; P = .01). The median (IQR) AF burden in the ablation group was lower than in the medical therapy group (0% [0%-3.22%] vs 15.5% [1.0%-45.9%]; P < .001). Conclusion and Relevance: In this trial of participants with symptomatic AF, improvement in psychological symptoms of anxiety and depression was observed with catheter ablation, but not medical therapy. Trial Registration: ANZCTR Identifier: ACTRN12618000062224.

Noninvasive ECG imaging of the intrinsic atrial pacemaker and atrial activation in surgically repaired or palliated congenital heart disease.

INTRODUCTION: Sinus node location, function, and atrial activation are often abnormal in patients with congenital heart disease (CHD), due to anatomical, surgical, and acquired factors. We aimed to perform noninvasive electrocardiographic imaging (ECGI) of the intrinsic atrial pacemaker and atrial activation in patients with surgically repaired or palliated CHD, compared with control patients with structurally normal hearts. METHODS AND RESULTS: Atrial ECGI was performed in eight CHD patients with prespecified diagnoses (Fontan circulation, dextro transposition of the great arteries post Mustard/Senning, tetralogy of Fallot), and three controls. Activation and propagation maps were constructed in presenting rhythm. Wavefront propagation was analyzed to identify (1) intrinsic atrial pacemaker breakout site, (2) morphological right atrial (RA) activation pattern, (3) morphological left atrial (LA) breakout sites (i.e., interatrial connections), (4) LA activation pattern, and (5) putative lines of block. Physiologically appropriate atrial activation and propagation maps were able to be constructed. In the majority of patients, atrial breakouts were in keeping with the sinus node, observed in a crescent-shaped distribution from the anterior superior vena cava to the posterior RA. Ectopic atrial pacemaker sites were demonstrated in the atriopulmonary (AP) Fontan patient (very diffuse posterolateral RA) and Mustard patient (very posterior RA competing with a low RA focus). RA propagation was laminar in controls, but suggested either a line of block or conduction slowing consistent with an atriotomy scar in the tetralogy of Fallot (TOF) patients. Putative lines of block were more complex and RA propagation more abnormal in the atrial switch and AP Fontan patients, compared with the TOF patients. RA activation in the extracardiac Fontan patients was relatively laminar. Earliest LA breakout was most commonly observed in the region of Bachmann's Bundle in both controls and CHD patients, except for posterior LA breakouts in two patients. LA activation was typically more homogeneous than RA activation in CHD patients. CONCLUSION: ECGI can be utilized to create a noninvasive mapping model of atrial activation in postsurgical CHD, demonstrating atrial pacemaker location, putative lines of block and interatrial connections. Once validated invasively, this may have clinical implications in predicting risk of sinus node dysfunction and atrial arrhythmias, or in guiding catheter ablation.