Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation.

BACKGROUND: The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown. METHODS: We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patients were assigned to receive catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary end point was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation. RESULTS: A total of 97 patients were assigned to the ablation group and 97 to the medical-therapy group. The trial was stopped for efficacy by the data and safety monitoring board 1 year after randomization was completed. Catheter ablation was performed in 81 of 97 patients (84%) in the ablation group and in 16 of 97 patients (16%) in the medical-therapy group. After a median follow-up of 18.0 months (interquartile range, 14.6 to 22.6), a primary end-point event had occurred in 8 patients (8%) in the ablation group and in 29 patients (30%) in the medical-therapy group (hazard ratio, 0.24; 95% confidence interval [CI], 0.11 to 0.52; P<0.001). Death from any cause occurred in 6 patients (6%) in the ablation group and in 19 patients (20%) in the medical-therapy group (hazard ratio, 0.29; 95% CI, 0.12 to 0.72). Procedure-related complications occurred in 3 patients in the ablation group and in 1 patient in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation and end-stage heart failure, the combination of catheter ablation and guideline-directed medical therapy was associated with a lower likelihood of a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. (Funded by Else Kröner-Fresenius-Stiftung; CASTLE-HTx ClinicalTrials.gov number, NCT04649801.).

One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

Comprehensive atrial fibrillation burden and symptom reduction post-ablation: insights from DECAAF II.

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.

Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study.

BACKGROUND: The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown. METHODS: Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were "watch-naïve" at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study. CONCLUSION: The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276441.

Differences in postablation cardiac MRI scar between radiofrequency and cryoballoon ablation: A DECAAF II subanalysis.

INTRODUCTION: Pulmonary vein isolation (PVI) using radiofrequency (RF) and cryoballoon (Cryo) ablation are standard approaches for rhythm control in patients with symptomatic atrial fibrillation. Both strategies create scars in the left atrium (LA). There have been few studies investigating the difference in scar formation between patients undergoing RF and Cryo using cardiac magnetic resonance (CMR) imaging. METHODS: The current study is a subanalysis of the control arm of the Delayed-Enhancement MRI Determinant of Successful Catheter Ablation of Atrial Fibrillation study (DECAAF II). The study was a multicenter, randomized, controlled, single-blinded trial that evaluated atrial arrhythmia recurrence (AAR) between PVI alone and PVI plus CMR atrial fibrosis-guided ablation. Preablation CMR and 3- to 6-month postablation CMR were obtained to assess baseline LA fibrosis and scar formation, respectively. RESULTS: Of the 843 patients randomized in the DECAAF II trial, we analyzed the 408 patients in the primary analysis control arm that received standard PVI. Five patients received combined RF and Cryo ablations, so they were excluded from this subanalysis. Of the 403 patients analyzed, 345 underwent RF and 58 Cryo. The average procedure duration was 146 min for RF and 103 min for Cryo (p = .001). The rate of AAR at ~15 months occurred in 151 (43.8%) patients in the RF group and 28 (48.3%) patients in the Cryo group (p = .62). On 3-month post-CMR, the RF arm had significantly more scar (8.8% vs. 6.4%, p = .001) compared to Cryo. Patients with ≥6.5% LA scar (p < .001) and ≥2.3% LA scar around the PV antra (p = .01) on 3-month post-CMR had less AAR independent of the ablation technique. Cryo caused a greater percentage of right and left pulmonary vein (PV) antral scar (p = .04, p = .02) and less non-PV antral scar (p = .009) compared to RF. On Cox regression, Cryo patients free of AAR had a greater percentage of left PV antral scar (p = .01) and less non-PV antral scar (p = .004) compared to RF free of AAR. CONCLUSION: In this subanalysis of the control arm of the DECAAF II trial, we observed that Cryo formed a more significant percentage of PV antral scar and less non-PV antral scar compared to RF. Post ablation LA scar ≥6.5% predicted freedom from AAR, independent of ablation technique. These findings may have prognostic implications in ablation technique selection and freedom from AAR.

Twenty-five years of research in cardiac imaging in electrophysiology procedures for atrial and ventricular arrhythmias.

Catheter ablation is nowadays considered the treatment of choice for numerous cardiac arrhythmias in different clinical scenarios. Fluoroscopy has traditionally been the primary imaging modality for catheter ablation, providing real-time visualization of catheter navigation. However, its limitations, such as inadequate soft tissue visualization and exposure to ionizing radiation, have prompted the integration of alternative imaging modalities. Over the years, advancements in imaging techniques have played a pivotal role in enhancing the safety, efficacy, and efficiency of catheter ablation procedures. This manuscript aims to explore the utility of imaging, including electroanatomical mapping, cardiac computed tomography, echocardiography, cardiac magnetic resonance, and nuclear cardiology exams, in helping electrophysiology procedures. These techniques enable accurate anatomical guidance, identification of critical structures and substrates, and real-time monitoring of complications, ultimately enhancing procedural safety and success rates. Incorporating advanced imaging technologies into routine clinical practice has the potential to further improve clinical outcomes of catheter ablation procedures and pave the way for more personalized and precise ablation therapies in the future.

Effect of fibrosis regionality on atrial fibrillation recurrence: insights from DECAAF II.

AIMS: The amount of fibrosis in the left atrium (LA) predicts atrial fibrillation (AF) recurrence after catheter ablation (CA). We aim to identify whether regional variations in LA fibrosis affect AF recurrence. METHODS AND RESULTS: This post hoc analysis of the DECAAF II trial includes 734 patients with persistent AF undergoing first-time CA who underwent late gadolinium enhancement magnetic resonance imaging (LGE-MRI) within 1 month prior to ablation and were randomized to MRI-guided fibrosis ablation in addition to standard pulmonary vein isolation (PVI) or standard PVI only. The LA wall was divided into seven regions: anterior, posterior, septal, lateral, right pulmonary vein (PV) antrum, left PV antrum, and left atrial appendage (LAA) ostium. Regional fibrosis percentage was defined as a region's fibrosis prior to ablation divided by total LA fibrosis. Regional surface area percentage was defined as an area's surface area divided by the total LA wall surface area before ablation. Patients were followed up for a year with single-lead electrocardiogram (ECG) devices. The left PV had the highest regional fibrosis percentage (29.30 ± 14.04%), followed by the lateral wall (23.23 ± 13.56%), and the posterior wall (19.80 ± 10.85%). The regional fibrosis percentage of the LAA was a significant predictor of AF recurrence post-ablation (odds ratio = 1.017, P = 0.021), and this finding was only preserved in patients receiving MRI-guided fibrosis ablation. Regional surface area percentages did not significantly affect the primary outcome. CONCLUSION: We have confirmed that atrial cardiomyopathy and remodelling are not a homogenous process, with variations in different regions of the LA. Atrial fibrosis does not uniformly affect the LA, and the left PV antral region has more fibrosis than the rest of the wall. Furthermore, we identified regional fibrosis of the LAA as a significant predictor of AF recurrence post-ablation in patients receiving MRI-guided fibrosis ablation in addition to standard PVI.

Identifying the prognostic significance of early arrhythmia recurrence during the blanking period and the optimal blanking period duration: insights from the DECAAF II study.

OBJECTIVE: Early atrial arrhythmia recurrence following atrial fibrillation (AF) ablation is common. Current guidelines promulgate a 3-month blanking period. We hypothesize that early atrial arrhythmia recurrence during the blanking period may predict longer-term ablation outcomes. METHODS AND RESULTS: A total of 688 patients with persistent AF undergoing catheter ablation were included in the DECAAF II trial database. The primary endpoint of the study was the first confirmed recurrence of atrial arrhythmia. Recurrence was also monitored during the 90-day blanking period. A total of 287 patients experienced recurrent atrial arrhythmia during the blanking period, while 401 remained in sinus rhythm. Rates of longer-term arrhythmia recurrence were substantially higher among those who developed recurrence during the blanking period compared to those who remained in sinus rhythm throughout the blanking period (68% vs. 32%, P < 0.001). The study cohort was divided into three groups according to the timing of arrhythmia recurrence during the blanking period. Of those who had recurrent arrhythmia during the first month of the blanking period (Group 1), 43.9% experienced longer-term recurrence, compared to 61.6% who recurred during the second month of the blanking period (Group 2), and 93.3% of those who had arrhythmia recurrence during the third month (Group 3, P < 0.001). The risk of recurrent arrhythmia was highest in Group 3 (HR = 10.15), followed by Group 2 (HR = 2.35) and Group 1 (HR = 1.5). Receiver operating characteristic analysis was performed to assess the relationship between the timing of arrhythmia recurrence and the primary outcome (AUC = 0.746, P < 0.001). The optimal blanking period duration was identified as 34 days. Atrial fibrillation burden determined by smartphone electrocardiogram technology over the 18 months follow-up period was significantly higher in Group 3 (29%) compared to Groups 1 (6%) and 2 (7%) and in patients who stayed in sinus rhythm during the blanking period (5%) (P < 0.0001). CONCLUSION: Early atrial arrhythmia recurrence during the blanking period, particularly during the third month, is significantly associated with later recurrence. Although a blanking period is warranted, it should be abbreviated.

Catheter ablation improved ejection fraction in persistent AF patients: a DECAAF-II sub analysis.

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.

Baseline natriuretic peptides as a predictor of atrial fibrillation recurrence after radiofrequency-based pulmonary vein isolation in a non-heart failure population: A subanalysis from DECAAF II.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of myocardial stretch and may have prognostic significance in patients with atrial fibrillation (AF) without heart failure (HF). We investigated the association between baseline BNP levels and arrhythmia recurrence following pulmonary vein isolation (PVI) among patients with persistent AF without HF. METHODS: We analyzed 125 patients with persistent AF without HF who had baseline BNP measured from the DECAAF II trial. The primary outcome was arrhythmia recurrence following ablation. The baseline characteristics across the two groups were compared using Chi-square test and Wilcoxon rank test accordingly. Cox regression analysis was used to analyze the association between baseline BNP levels and the primary outcome. RESULTS: Across the entire cohort, 64 (51%) patients experienced arrhythmia recurrence. When comparing patients who experienced arrythmia recurrence to patients who did not, patients with recurrent arrhythmia had higher levels of pre-ablation BNP, as evidenced by differences in means (330.05 pg/mL) compared to patients without recurrent arrhythmia (182.39 pg/mL) (p < .05). A cut-off BNP value of 300 pg/mL provided the largest area under curve (AUC) of receiver-operating characteristic (ROC) curve on univariate logistic regression. On unadjusted Cox analysis, for every 100 unit increase in BNP, the hazard ratio for the primary outcome increased 1.09 (1.026-1.158) times (p = .004). After adjusting for sex, hypertension, and stroke, the results remained significant (HR = 1.8516, CI 95% [1.0139 - 3.381], p = .045). CONCLUSION: In the non-heart failure population, BNP levels predict AF recurrence following PVI in persistent AF patients.

Compliance Challenges in a Longitudinal COVID-19 Cohort Using Wearables for Continuous Monitoring: Observational Study.

BACKGROUND: The WEAICOR (Wearables to Investigate the Long Term Cardiovascular and Behavioral Impacts of COVID-19) study was a prospective observational study that used continuous monitoring to detect and analyze biometrics. Compliance to wearables was a major challenge when conducting the study and was crucial for the results. OBJECTIVE: The aim of this study was to evaluate patients' compliance to wearable wristbands and determinants of compliance in a prospective COVID-19 cohort. METHODS: The Biostrap (Biostrap USA LLC) wearable device was used to monitor participants' biometric data. Compliance was calculated by dividing the total number of days in which transmissions were sent by the total number of days spent in the WEAICOR study. Univariate correlation analyses were performed, with compliance and days spent in the study as dependent variables and age, BMI, sex, symptom severity, and the number of complications or comorbidities as independent variables. Multivariate linear regression was then performed, with days spent in the study as a dependent variable, to assess the power of different parameters in determining the number of days patients spent in the study. RESULTS: A total of 122 patients were included in this study. Patients were on average aged 41.32 years, and 46 (38%) were female. Age was found to correlate with compliance (r=0.23; P=.01). In addition, age (r=0.30; P=.001), BMI (r=0.19; P=.03), and the severity of symptoms (r=0.19; P=.03) were found to correlate with days spent in the WEAICOR study. Per our multivariate analysis, in which days spent in the study was a dependent variable, only increased age was a significant determinant of compliance with wearables (adjusted R2=0.1; ß=1.6; P=.01). CONCLUSIONS: Compliance is a major obstacle in remote monitoring studies, and the reasons for a lack of compliance are multifactorial. Patient factors such as age, in addition to environmental factors, can affect compliance to wearables.

Studying the Effect of Long COVID-19 Infection on Sleep Quality Using Wearable Health Devices: Observational Study.

BACKGROUND: Patients with COVID-19 have increased sleep disturbances and decreased sleep quality during and after the infection. The current published literature focuses mainly on qualitative analyses based on surveys and subjective measurements rather than quantitative data. OBJECTIVE: In this paper, we assessed the long-term effects of COVID-19 through sleep patterns from continuous signals collected via wearable wristbands. METHODS: Patients with a history of COVID-19 were compared to a control arm of individuals who never had COVID-19. Baseline demographics were collected for each subject. Linear correlations among the mean duration of each sleep phase and the mean daily biometrics were performed. The average duration for each subject's total sleep time and sleep phases per night was calculated and compared between the 2 groups. RESULTS: This study includes 122 patients with COVID-19 and 588 controls (N=710). Total sleep time was positively correlated with respiratory rate (RR) and oxygen saturation (SpO2). Increased awake sleep phase was correlated with increased heart rate, decreased RR, heart rate variability (HRV), and SpO2. Increased light sleep time was correlated with increased RR and SpO2 in the group with COVID-19. Deep sleep duration was correlated with decreased heart rate as well as increased RR and SpO2. When comparing different sleep phases, patients with long COVID-19 had decreased light sleep (244, SD 67 vs 258, SD 67; P=.003) and decreased deep sleep time (123, SD 66 vs 128, SD 58; P=.02). CONCLUSIONS: Regardless of the demographic background and symptom levels, patients with a history of COVID-19 infection demonstrated altered sleep architecture when compared to matched controls. The sleep of patients with COVID-19 was characterized by decreased total sleep and deep sleep.

Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The DECAAF II Randomized Clinical Trial.

Importance: Ablation of persistent atrial fibrillation (AF) remains a challenge. Left atrial fibrosis plays an important role in the pathophysiology of AF and has been associated with poor procedural outcomes. Objective: To investigate the efficacy and adverse events of targeting atrial fibrosis detected on magnetic resonance imaging (MRI) in reducing atrial arrhythmia recurrence in persistent AF. Design, Setting, and Participants: The Efficacy of Delayed Enhancement-MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation of Atrial Fibrillation trial was an investigator-initiated, multicenter, randomized clinical trial involving 44 academic and nonacademic centers in 10 countries. A total of 843 patients with symptomatic or asymptomatic persistent AF and undergoing AF ablation were enrolled from July 2016 to January 2020, with follow-up through February 19, 2021. Interventions: Patients with persistent AF were randomly assigned to pulmonary vein isolation (PVI) plus MRI-guided atrial fibrosis ablation (421 patients) or PVI alone (422 patients). Delayed-enhancement MRI was performed in both groups before the ablation procedure to assess baseline atrial fibrosis and at 3 months postablation to assess for ablation scar. Main Outcomes and Measures: The primary end point was time to first atrial arrhythmia recurrence after a 90-day blanking period postablation. The primary safety composite outcome was defined by the occurrence of 1 or more of the following events within 30 days postablation: stroke, PV stenosis, bleeding, heart failure, or death. Results: Among 843 patients who were randomized (mean age 62.7 years; 178 [21.1%] women), 815 (96.9%) completed the 90-day blanking period and contributed to the efficacy analyses. There was no significant difference in atrial arrhythmia recurrence between groups (fibrosis-guided ablation plus PVI patients, 175 [43.0%] vs PVI-only patients, 188 [46.1%]; hazard ratio [HR], 0.95 [95% CI, 0.77-1.17]; P = .63). Patients in the fibrosis-guided ablation plus PVI group experienced a higher rate of safety outcomes (9 [2.2%] vs 0 in PVI group; P = .001). Six patients (1.5%) in the fibrosis-guided ablation plus PVI group had an ischemic stroke compared with none in PVI-only group. Two deaths occurred in the fibrosis-guided ablation plus PVI group, and the first one was possibly related to the procedure. Conclusions and Relevance: Among patients with persistent AF, MRI-guided fibrosis ablation plus PVI, compared with PVI catheter ablation only, resulted in no significant difference in atrial arrhythmia recurrence. Findings do not support the use of MRI-guided fibrosis ablation for the treatment of persistent AF. Trial Registration: ClinicalTrials.gov Identifier: NCT02529319.

Catheter Ablation for Atrial Fibrillation with Heart Failure.

BACKGROUND: Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment. METHODS: We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: After a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009). CONCLUSIONS: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).

Effect of DrOnedarone on atrial fibrosis progression and atrial fibrillation recurrence postablation: Design of the EDORA randomized clinical trial.

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.

Atrial fibrosis progression in patients with no history of atrial fibrillation.

BACKGROUND: Unexpected high levels of atrial fibrosis are found in individuals with no history of atrial fibrillation (AF). The temporal behavior of atrial fibrosis in this population is still unknown. We sought to investigate the progression and predictors of atrial fibrosis in non-AF individuals. METHODS: Non-AF individuals at baseline who underwent late gadolinium enhancement magnetic resonance imaging (LGE-MRI) for assessment of left atrial (LA) fibrosis at least twice were retrospectively included in this study. The incidence of AF was assessed using review of medical records. RESULTS: In 42 non-AF patients (15 females, 65.9 ± 8.6 years old), all patients had a detectable level of LA fibrosis at baseline, ranging from 4.5% to 28.8%, with a mean of 12.9 ± 5.9%. LA fibrosis in the second LGE-MRI was significantly higher in all patients compared to the first measurement (mean value of 12.9 ± 5.9% vs. 17.34 ± 6.8%; p < .05). Congestive heart failure was a significant clinical predictor of atrial fibrosis progression. The seven patients (16.6%) who developed new-onset AF during follow-up showed a significantly higher degree of LA fibrosis on their second MRI, compared to individuals who stayed in sinus rhythm (20.5 ± 6.9% vs. 16.7 ± 6.7%, p < .05). CONCLUSION: Atrial fibrotic remodeling is a dynamic process that is progressively increasing in non-AF patients, accentuated by congestive heart failure. The higher extent of LA remodeling observed in patients who developed AF could highlight either the fact that AF is an expression of a highly dynamic left atrial substrate, or that remodeling processes are accelerated by AF.

Efficacy of LGE-MRI-guided fibrosis ablation versus conventional catheter ablation of atrial fibrillation: The DECAAF II trial: Study design.

INTRODUCTION: Success rates of catheter ablation in persistent atrial fibrillation (AF) remain suboptimal. A better and more targeted ablation strategy is urgently needed to optimize outcomes of AF treatment. We sought to assess the safety and efficacy of targeting atrial fibrosis during ablation of persistent AF patients in improving procedural outcomes. METHODS: The DECAAF II trial (ClinicalTrials. gov identifier number NCT02529319) is a prospective, randomized, multicenter trial of patients with persistent AF. Patients with persistent AF undergoing a first-time ablation procedure were randomized in a 1:1 fashion to receive conventional pulmonary vein isolation (PVI) ablation (Group 1) or PVI + fibrosis-guided ablation (Group 2). Left atrial fibrosis and ablation induced scarring were defined by late gadolinium enhancement magnetic resonance imaging at baseline and at 3-12 months postablation, respectively. The primary endpoint is the recurrence of atrial arrhythmia postablation, including atrial fibrillation, atrial flutter, or atrial tachycardia after the 90-day postablation blanking period. Patients were followed for a period of 12-18 months with a smartphone ECG Device (ECG Check Device, Cardiac Designs Inc.). With an anticipated enrollment of 900 patients, this study has an 80% power to detect a 26% reduction in the hazard ratio of the primary endpoint. RESULTS AND CONCLUSION: The DECAAF II trial is the first prospective, randomized, multicenter trial of patients with persistent AF using imaging defined atrial fibrosis as a treatment target. The trial will help define an optimal approach to catheter ablation of persistent AF, further our understanding of influencers of ablation lesion formation, and refine selection criteria for ablation based on atrial myopathy burden.

High-degree atrioventricular block in COVID-19 hospitalized patients.

AIMS: The novel coronavirus SARS-CoV-2 has shown the potential to significantly affect the cardiovascular system. Cardiac arrhythmias are commonly reported complications in COVID-19 hospitalized patients. METHODS AND RESULTS: While tachyarrhythmias seem most common, we describe four cases of COVID-19 patients who developed a transient high-degree atrioventricular (AV) block during the course of their hospitalization. All four patients who developed a high-degree AV block during their hospitalization with COVID-19 did not require permanent pacing. CONCLUSION: Similarly to most AV blocks associated with infectious organisms and given its transient nature, this case series suggests that conservative management strategies should be preferred in COVID-19 patients who develop complete heart block.

New-onset atrial arrhythmias associated with mortality in black and white patients hospitalized with COVID-19.

BACKGROUND: Specific details about cardiovascular complications, especially arrhythmias, related to the coronavirus disease of 2019 (COVID-19) are not well described. OBJECTIVE: We sought to evaluate the incidence and predictive factors of cardiovascular complications and new-onset arrhythmias in Black and White hospitalized COVID-19 patients and determine the impact of new-onset arrhythmia on outcomes. METHODS: We collected and analyzed baseline demographic and clinical data from COVID-19 patients hospitalized at the Tulane Medical Center in New Orleans, Louisiana, between March 1 and May 1, 2020. RESULTS: Among 310 hospitalized COVID-19 patients, the mean age was 61.4 ± 16.5 years, with 58,7% females, and 67% Black patients. Black patients were more likely to be younger, have diabetes and obesity. The incidence of cardiac complications was 20%, with 9% of patients having new-onset arrhythmia. There was no significant difference in cardiovascular outcomes between Black and White patients. A multivariate analysis determined age ≥60 years to be a predictor of new-onset arrhythmia (OR = 7.36, 95% CI [1.95;27.76], p = .003). D-dimer levels positively correlated with cardiac and new-onset arrhythmic event. New onset atrial arrhythmias predicted in-hospital mortality (OR = 2.99 95% CI [1.35;6.63], p = .007), a longer intensive care unit length of stay (mean of 6.14 days, 95% CI [2.51;9.77], p = .001) and mechanical ventilation duration(mean of 9.08 days, 95% CI [3.75;14.40], p = .001). CONCLUSION: Our results indicate that new onset atrial arrhythmias are commonly encountered in COVID-19 patients and can predict in-hospital mortality. Early elevation in D-dimer in COVID-19 patients is a significant predictor of new onset arrhythmias. Our finding suggest continuous rhythm monitoring should be adopted in this patient population during hospitalization to better risk stratify hospitalized patients and prompt earlier intervention.

Atrial fibrillation and cardiac fibrosis.

The understanding of atrial fibrillation (AF) evolved from a sole rhythm disturbance towards the complex concept of a cardiomyopathy based on arrhythmia substrates. There is evidence that atrial fibrosis can be visualized using late gadolinium enhancement cardiac magnetic resonance imaging and that it is a powerful predictor for the outcome of AF interventions. However, a strategy of an individual and fibrosis guided management of AF looks promising but results from prospective multicentre trials are pending. This review gives an overview about the relationship between cardiac fibrosis and AF focusing on translational aspects, clinical observations, and fibrosis imaging to emphasize the concept of personalized paths in AF management taking into account the individual amount and distribution of fibrosis.