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Introduction: Catheter ablation of persistent atrial fibrillation yields sub-optimal success rates partly due to the considerable heterogeneity within the patient population. Identifying distinct patient phenotypes based on post-ablation prognosis could improve patient selection for additional therapies and optimize treatment strategies., Methods: We studied all patients who underwent catheter ablation of persistent atrial fibrillation in the DECAAF II trial. Out of 44 participating centers, 25% were randomly chosen as a validation set. A Gradient Boosting Method determined essential features for arrhythmia recurrence prediction and the number of clusters was determined according to the average silhouette width. K-medoids cluster analysis identified subgroups based on these features, and Kaplan-Meier curves were further compared among different clusters., Results: Among 815 patients, 570 served as a training set and 245 as a validation set. Using the training set, the GBM model achieved an AUC of 0.874. K-medoids cluster analysis used LA volume, BMI, baseline fibrosis, and age, resulting in two clusters. Cluster 1 patients were older, had higher baseline fibrosis, higher BMI, and greater LA volume compared to Cluster 2. Atrial arrhythmia recurrence rates were significantly higher in Cluster 1 (51.7% vs. 35.0%, p = 0.0002), and survival analysis showed a significant difference in primary recurrence outcomes (HR = 1.71, p < 0.0001). The validation set confirmed these findings., Conclusion: Utilizing machine learning, we identified a high-risk cluster for procedural failure in catheter ablation of persistent atrial fibrillation within the DECAAF II trial population. The primary differentiating factors of this high-risk cluster include older age, high left atrial fibrosis, elevated BMI, and increased left atrial volume., (© 2024 Wiley Periodicals LLC.)

Background: There is a strong relationship between left atrial (LA) remodeling and ischemic stroke (IS) risk in atrial fibrillation (AF) patients. The Efficacy of Delayed Enhancement MRI-Guided Ablation vs. Conventional Catheter Ablation of Atrial Fibrillation (DECAAF-II) is the biggest MRI-based, randomized, multicenter clinical trial performed on persistent AF patients. The aim of this study is to evaluate the relationship between history of stroke and atrial fibrosis in the DECAAF II population., Methods: Persistent AF patients who underwent Late Gadolinium Enhancement Magnetic Resonance Imaging (LGE-MRI) were included in the study and divided into two different groups: those with a history of stroke and those without. Propensity score matching was performed to adjust for covariates. Atrial fibrosis was compared in both groups. Then, patients were divided into different fibrosis groups, using three different cut-offs of baseline atrial fibrosis: ≥ 15%, ≥ 20%, and ≥ 25%. Univariate logistic regression and adjusted multivariate analysis were performed to assess the effect of clinical characteristics and risk factors on baseline fibrosis., Results: Eight-hundred forty-three patients were recruited in DECAAF II, of whom 70 (8.3%) had a history of stroke. Patients with history of stroke had a higher prevalence of hypertension (p = 0.043), diabetes (p = 0.014), and hyperlipidemia (p = 0.001). Seventy patients with no history of strokes were matched with patients with history of stroke to adjust for covariates using propensity score analysis. Patients in the stroke group had a significantly higher level of fibrosis than those without (20.2% vs. 8.1%, p = 0.017). Increased age was a significant predictor of all three baseline fibrosis classes (≥ 15%, ≥ 20%, and ≥ 25%). Additionally, history of stroke was found to be a predictor of baseline fibrosis ≥ 25% even after adjusting for other clinical characteristics and risk factors (OR = 1.98 [1.14-3.43], p = 0.01)., Conclusions: Left atrial fibrosis level greater than 25% correlates with the history of previous stroke episodes in patients with persistent atrial fibrillation., Competing Interests: Declarations. Conflict of interest: NM reports having received consulting fees from Biosense Webster, Boston Scientific, and AtriCure. NM also reports being a speaker for Abbott, Biosense Webster, AtriCure, and Sanofi. NM also reports receiving research support Abbott, Medtronic, Biosense Webster, Siemens, GE, Boston Scientific, Sanofi, and Samsung. NM also reports having a family member as the CEO of Cardiac Designs. NM also reports being the founder of Marrek, being named in a patent issued for MRI fibrosis imaging, and being a previous shareholder of Cardiac Designs. All other co-authors have no relevant conflict of interest. The DECAAF II trial was funded by Medtronic, GE, Siemens, Boston Scientific, Biosense Webster, and Abbott., (© 2024. The Author(s).)

Background: Catheter ablation (CA) improves clinical outcomes in patients with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to evaluate the impact of CA on clinical and quality-of-life outcomes across HF subtypes., Methods: All patients undergoing AF ablation at a tertiary center were enrolled in a prospective registry and included in this study (2013-2021). The primary end point was AF recurrence. Secondary end points included AF-related hospitalizations and quality-of-life outcomes. Patients were categorized according to their HF status: no HF, HFrEF, HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF)., Results: A total of 7020 patients were included (80% no HF, 8% HFrEF, 7% HFmrEF, and 5% HFpEF). Over 3 years, the cumulative incidence of AF recurrence after ablation was as follows: HFpEF (53%), HFmrEF (41%), HFrEF (41%), and no HF (34%); P <0.01. Multivariable Cox analyses confirmed these findings using no HF group as reference (HFpEF: hazard ratio, 1.47 [95% CI, 1.21-1.78]; HFmrEF: hazard ratio, 1.23 [95% CI, 1.04-1.45]; and HFrEF: hazard ratio, 1.17 [95% CI, 1.01-1.37]; P <0.05 for all). In all groups, CA resulted in a significant reduction of AF-related hospitalization (mean rate per 1 patient-years [before and after CA]; HFpEF [1.8 versus 0.3], HFmrEF [1.1 versus 0.2], HFrEF [1.1 versus 0.2], and no HF [1 versus 0.1]; P <0.01 for each comparison) and significant improvement in quality of life as measured by both the AF symptom severity score and the AF burden score ( P <0.01 for the comparison between baseline and follow-up for each score when tested separately)., Conclusions: AF recurrence rates after CA were higher in patients with HF compared with those without HF, with patients with HFpEF being at the highest risk of recurrence. Nonetheless, CA was associated with a significant reduction in AF symptoms, AF-related hospitalization, and HF symptoms in most patients irrespective of HF subtypes., Competing Interests: Dr Hussein receives research grant support from Boston Scientific. The other authors report no conflicts.

Aims: Traditional atrial fibrillation (AF) recurrence after catheter ablation is reported as a binary outcome. However, a paradigm shift towards a more granular definition, considering arrhythmic or symptomatic burden, is emerging. We hypothesize that ablation reduces AF burden independently of conventional recurrence status in patients with persistent AF, correlating with symptom burden reduction., Methods and Results: Ninety-eight patients with persistent AF from the DECAAF II trial with pre-ablation follow-up were included. Patients recorded daily single-lead electrocardiogram (ECG) strips, defining AF burden as the proportion of AF days among total submitted ECG days. The primary outcome was atrial arrhythmia recurrence. The AF severity scale was administered pre-ablation and at 12 months post-ablation. At follow-up, 69 patients had atrial arrhythmia recurrence and 29 remained in sinus rhythm. These patients were categorized into a recurrence (n = 69) and a no-recurrence group (n = 29). Both groups had similar baseline characteristics, but recurrence patients were older (P = 0.005), had a higher prevalence of hyperlipidaemia (P = 0.007), and had a larger left atrial (LA) volume (P = 0.01). There was a reduction in AF burden in the recurrence group when compared with their pre-ablation burden (65 vs. 15%, P < 0.0001). Utah Stage 4 fibrosis and diabetes predicted less improvement in AF burden. The symptom severity score at 12 months post-ablation was significantly reduced compared with the pre-ablation score in the recurrence group, and there was a significant correlation between the reduction in symptom severity score and the reduction in AF burden (R = 0.39, P = 0.001)., Conclusion: Catheter ablation reduces AF burden, irrespective of arrhythmia recurrence post-procedure. There is a strong correlation between AF burden reduction and symptom improvement post-ablation. Notably, elevated LA fibrosis impedes AF burden decrease following catheter ablation., Competing Interests: Conflict of interest: N.M. reported Marrek (founder) and ECG Check (previous shareholder) outside the submitted work; a patent was issued for MRI fibrosis imaging. No other disclosures were reported., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The aim of our study was to assess differences in post-ablation atrial fibrillation (AF) recurrence and burden and to quantify the change in LVEF across different congestive heart failure (CHF) subcategories of the DECAAF-II population., Methods and Results: Differences in the primary outcome of AF recurrence between CHF and non-CHF groups was calculated. The same analysis was performed for the three subgroups of CHF and the non-CHF group. Differences in AF burden after the 3-month blanking period between CHF and non-CHF groups was calculated. Improvement in LVEF was calculated and compared across the three CHF groups. Improvement was also calculated across different fibrosis stages. There was no significant differences in AF recurrence and AF burden after catheter ablation between CHF and non-CHF patients and between different CHF subcategories. Patients with heart failure with reduced ejection fraction (HFrEF) experienced the greatest improvement in EF following catheter ablation (CA, 16.66% ± 11.98, P < 0.001) compared to heart failure with moderately reduced LVEF, and heart failure with preserved EF (10.74% ± 8.34 and 2.00 ± 8.34 respectively, P-value < 0.001). Moreover, improvement in LVEF was independent of the four stages of atrial fibrosis (7.71 vs. 9.53 vs. 5.72 vs. 15.88, from Stage I to Stage IV respectively, P = 0.115)., Conclusion: Atrial fibrillation burden and recurrence after CA is similar between non-CHF and CHF patients, independent of the type of CHF. Of all CHF groups, those with HFrEF had the largest improvement in LVEF after CA. Moreover, the improvement in ventricular function seems to be independent of atrial fibrosis in patients with persistent AF., Competing Interests: Conflicts of interest: Dr. Marrouche reports receiving grant support and consulting fees from Abbott, Medtronic, Biosense Webster, Boston Scientific, and Siemens, receiving consulting fees from Preventice, and holding equity Cardiac Design. All other authors have no conflicts of interest associated with the content of this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Lower neighborhood median household income (nMHI) is associated with increased adverse outcomes in patients with atrial fibrillation (AF). However, its effect on mortality is yet unknown., Methods: Data from the regional United States (U.S.) electronic medical records database, Research Action for Health Network (REACHnet), was extracted for adult patients with AF at Tulane Medical Center over 10 years. Annual nMHI & neighborhood high school graduation (HSG) data was collected from the US Census bureau. Only African Americans (AA) and Caucasians (CC) who had socioeconomic data were included. Low nMHI and low HSG were defined as ≤$25,000 & <90% respectively. High nMHI and HSG were defined as >$50,000 & ≥90% respectively. Primary endpoints were all cause and cardiovascular (CV) mortality. Cox-proportional hazard ratios were used to evaluate the endpoints., Results: We included 4616 patients diagnosed with AF. During a median follow up of 4.6 years, 434 patients died of which 32.7% patients had CV mortality. There was a stepwise decrease in incidence of both all-cause and CV mortality as nMHI increased. Patients with low nMHI had the greatest risk of all-cause mortality (HR 1.9, C.I. 1.2-3.2, P 0.004). The association between low nMHI and all-cause mortality persisted after adjusting for age, sex, race, HSG and stroke risk factors using CHA 2 DS 2 VASC, delta CHA 2 DS 2 VASC scores and oral anticoagulant use. CV mortality followed a similar trend as all-cause mortality, however, this association was not significant after adjusting for the above variables. Apart from low nMHI, CHA 2 DS 2 VASC delta CHA 2 DS 2 VASC were statistically significant independent predictors of both all-cause and CV mortality., Conclusion: Low nMHI is an independent risk factor for all cause and CV mortality in AF. Higher burden of co-morbidities is the driving force behind this disparity. Future studies should evaluate the role of educational and therapeutic intervention in these populations to reduce mortality., Competing Interests: Declaration of Competing Interest Dr. Marrouche reports consulting fees from Abbott, Biotronik, Wavelet Health, Cardiac Design, Medtronic, Preventice, Vytronus, Biosense Webster, Marrek Inc., and Boston Scientific; research funding from Abbott, Boston Scientific, GE Healthcare, Siemens, Biotronik, Vytronus, and Biosense Webster; ownership interest in Marrek Inc. and Cardiac Designs; contracted research with Biosense Webster, Medtronic, St. Jude Medical, and Boston Scientific; and reports consulting fees from Biotronik and Preventice. The remaining authors have no disclosures to report., (Published by Elsevier Inc.)

Background: Atrial fibrillation (AF) recurrence after catheter ablation is associated with worse outcomes and quality of life. Left atrial (LA) structural remodeling provides the essential substrate for AF perpetuation. Baseline extent and the progression of LA fibrosis after ablation are strong predictors of postprocedural AF recurrence. Dronedarone is an antiarrhythmic drug proven to efficiently maintain sinus rhythm., Objective: We sought to investigate the effect of the antiarrhythmic drug Dronedarone in decreasing LA fibrosis progression and AF recurrence after ablation of AF patients., Methods: EDORA (NCT04704050) is a multicenter, prospective, randomized controlled clinical trial. Patients with persistent or paroxysmal AF undergoing AF ablation will be randomized into Dronedarone versus placebo/standard of care. The co-primary outcomes are the recurrence of atrial arrhythmias (AA) within 13 months of follow-up after ablation and the progression of left atrial fibrosis postablation. All patients will receive a late-gadolinium enhancement magnetic resonance imaging at baseline, 3- and 12-month follow-up for the quantification of LA fibrosis and ablation-related scarring. AA recurrence and burden will be assessed using a 30-day ECG patch every 3 months with daily ECG recordings in between. Quality of life improvement is assessed using the AFEQT and AFSS questionnaires., Conclusion: EDORA will be the first trial to assess the progression of LA structural remodeling after ablation and its association with Dronedarone treatment and ablation success in a randomized controlled fashion. The trial will provide insight into the pathophysiology of AF recurrence after ablation and may provide potential therapeutic targets to optimize procedural outcomes., (© 2021 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals LLC.)