Population Of Atrial Fibrillation Patients Research Articles

Pulsed electric field, cryoballoon, and radiofrequency for paroxysmal atrial fibrillation ablation: a propensity score-matched comparison

Abstract Background and Aims Pulmonary vein isolation (PVI) is the most effective rhythm control strategy in paroxysmal atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel, non-thermal energy source to selectively ablate cardiac tissue. We report the first multicenter experience on PVI via the pentaspline FarapulseTM PFA system versus thermal-based technologies in a propensity score-matched population of paroxysmal AF patients. Methods Propensity score matching was adopted to compare PVI-only ablation outcomes via the FarawaveTM PFA system (Group PFA), cryoballoon ablation (Group CRYO), or focal radiofrequency (Group RF) (PFA:CRYO:RF Ratio=1:2:2). Results Among 1572 (mean age: 62.4±11.3 years; 42.5% females) PAF patients undergoing their first time PVI with either PFA (n=174), CRYO (n=655), or RF (n=743), propensity score matching yielded 174 PFA, 348 CRYO, and 348 RF patients. First-pass isolation was achieved in 98.8% of pulmonary veins (PVs) with PFA, 81.5% with CRYO, and 73.1% with RF (p<0.001). Procedural and dwell times were significantly shorter with PFA. Overall complication rates were 3.4% (n=6) with PFA, 8.6% (n=30) with CRYO, and 5.5% (n=19) with RF (p=0.052). The 1-year Kaplan-Meier estimated freedom from any atrial tachyarrhythmia was 79.3% with PFA, 74.7% with CRYO, and 72.4% with RF (log-rank p-value: 0.24). Among 145 repeat ablation procedures, PV reconnection rate was 19.1% after PFA, 27.5% after CRYO, and 34.8% after RF (p=0.01). Conclusion PFA contributed to significantly shorter procedural times. Follow-up data showed a similar arrhythmia freedom among groups, although a higher rate of PV reconnection was documented in post-CRYO and post-RF redo procedures.RecurrencePVs

Predicting bleeding risk in frail older patients with atrial fibrillation using data from the FRAIL-AF trial

Abstract Background Bleeding remains an important complication in anticoagulated patients with atrial fibrillation (AF). Hereto, multiple scores have been developed to predict bleeding risk and subsequently identify a subset of patients in whom additional effort may be warranted to lower the risk of bleeding. Bleeding risk is particularly high in frail older individuals with AF. Yet to what extent existing scores can accurately identify patients at high risk in this population is unknown. Purpose To validate existing bleeding risk scores for predicting bleeding in frail older AF patients using oral anticoagulants. Methods We used data from the FRAIL-AF trial that randomized frail AF patients ≥75 years of age between continuing vitamin K antagonist (VKA) treatment or switching to non-VKA oral anticoagulant (NOAC) treatment. The outcome was major or clinically relevant non-major bleeding. We validated 4 existing bleeding risk scores: ORBIT, ATRIA, AF-BLEED and (the recently derived) DOAC-score. We used cause specific cox proportional hazard models with all-cause mortality as a competing risk, with the number of points on each score as a univariate variable to calculate discrimination by means of the c-statistic for each score. Next, to assess clinical utility, we estimated the incidence bleeding rates for patients classified as low-risk and high-risk by each respective score. Results In total 661 patients continued VKA treatment, and 663 switched to any NOAC. An additional 66 patients, originally excluded from randomization due to an estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73 m2 but followed observationally were included in the current analysis. The median age was 82.3 years (interquartile range (IQR) 78.7 – 86.6), 61.4% were male. Median eGFR was 61 (IQR 49 – 57), 54% had hypertension, 14% a previous bleeding, and 1.2% liver disease. In total 172 first bleedings occurred. Discrimination of all risk scores was poor, both in VKA and in NOAC users. Table 1 shows the c-statistics across the different risk scores; ranging from 0.54 to 0.56. The observed risk of bleeding in the low-risk category varied widely, see Table 2. Conclusion Existing bleeding risk scores are unable to accurately predict the bleeding risk in frail older patients with AF. Novel risk tools are needed for this growing population of vulnerable AF patients at high risk of bleeding.

Electrogram dispersion mapping for repeat ablation in patients with persistent atrial fibrillation

Abstract Background/Introduction While pulmonary vein isolation (PVI) is a key guideline endpoint for atrial fibrillation (AF) ablation, strategies for repeat ablation are debated, particularly when PVs are isolated. Electrogram dispersion mapping identifies dynamic substrates using existing catheters, remote from the PVs and may confer benefit to additional ablation. Purpose To describe the outcome of repeat ablation using electrogram mapping to identify areas of mechanistic significance in persistent AF patients. Methods Patients undergoing repeat ablation for persistent AF were recruited from two international centers. A five spline catheter was used to mark areas of electrogram dispersion before any ablation using previously described criteria. After confirming PVI, or re-isolation of PVs if necessary, ablation of all dispersion areas was performed. If termination to atrial tachycardia (AT) occurred, this was mapped using conventional methods. Patients who terminated to sinus underwent reinduction pacing protocols to map any further AT or AF inducible. Patients were followed up at 12 months with continuous event monitors, and beyond 12 months based on local guidelines. Results In total, 167 AF patients were enrolled: age 66 ± 8 yrs; 32% female; mean LA diameter 4.8 cm. PVI was present in 108 (64%) of patients. All patients underwent LA mapping, and 75 (45%) underwent right atrial (RA) mapping. Patients had an average of 3.2 LA and 1.4 RA ablation sites. The total number of dispersion sites in patients was similar in patients with and without PVI, (4.1 ± 2 and 3.6 ± 1 respectively). AF terminated in 144 patients (86%), with an overall conversion to sinus rhythm obtained by ablation in 42% of the patients. Patients were followed for an average of 2.92 ± 0.9 years. At 12 months, 159 (95%) patients were AF free, and 124 (74%) remained free of atrial arrhythmia. Of those patients, only 8 (5%) had AF, with 35 (21%) recurring with AT or atrial flutter (AFL). Of the 70 patients who terminated to sinus with repeat ablation, only 2 (2.9%) recurred with AF and 26 (37.1%) had recurrence of atrial arrhythmia (AF/AT/AFL) as a whole throughout the entire follow-up period (P<0.05). Patients with and without PVI at redo procedure did not have a statistically significant difference in recurrence of AF (Figure 1, P = 0.80) nor recurrence of atrial arrhythmia (Figure 2, P = 0.63) during total follow up time by log rank test. Conclusions In a difficult to treat population of persistent AF patients requiring a repeat ablation procedure, electrogram mapping led to rates of freedom from AF at 12 months similar to first time ablation series. Additionally, those with PVI present at time of procedure had similar benefit from this approach compared to those with reconnected veins. This is the largest demonstration of a technique that confers benefit in a PVI isolated subgroup of purely redo ablations for persistent AF.Figure 1:Percent AF FreeFigure 2:Percent AF/AT/AFL Free

Risk Profiles and Treatment Patterns in Atrial Fibrillation Patients with Chronic Kidney Disease Receiving or not Receiving Anticoagulation Therapy.

Background Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are at high risk for both thromboembolism and bleeding events. The latter induces a potential reason for withholding oral anticoagulation (OAC) despite an indication for prophylaxis of thromboembolic events. Methods AF patients with CKD (estimated glomerular filtration [eGFR] rate between 15 and 49 mL/min per 1.73 m 2 ) were included in a prospective international registry in Europe between 2016 and 2020, that is, XARENO (factor XA inhibition in renal patients with nonvalvular atrial fibrillation observational registry). The study enrolled adult patients treated at the discretion of physicians with rivaroxaban, vitamin K antagonists (VKA), or without OAC (w/oOAC). Here, we report a prespecified explorative baseline comparison between patients receiving OAC or no OAC within XARENO. Results In total, 1,544 patients (mean age: 78.2 years, mean eGFR: 36.2 mL/min) were studied (rivaroxaban n = 764, VKA n = 691, w/oOAC n = 89). Patients in the w/oOAC group were older and had a similar stroke (mean CHA 2 DS 2 -VASc score 4.0) but higher bleeding risk (mean modified Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score 2.5 vs. 1.8) compared with the OAC groups. The distribution of comorbidities including hypertension, diabetes, and heart failure was similar. Treatment with antiplatelet drugs was fivefold more frequent in the w/oOAC group. Conclusion Only 5.8% of the overall population of AF patients with advanced CKD received no OAC. These patients were older and had a higher bleeding risk, which might explain this decision, but which contrasts with the more frequent use of antiplatelet drugs in this vulnerable group of patients.

Comparison of efficacy of pharmacological cardioversion with antazoline and propafenone versus electrical cardioversion in atrial fibrillation during cryoablation.

Antazoline with propafenone may be an alternative to electrical cardioversion (ECV) in restoring sinus rhythm in patients with atrial fibrillation (AF), including during balloon cryoablation. To compare the efficacy of antazoline with propafenone and ECV in restoring and maintaining sinus rhythm at discharge in patients with AF during cryoablation with special regard to type of AF. The study retrospectively analyzed 196 patients who underwent elective cryoablation. Eighty-nine patients who developed AF in the perioperative period were selected as the study group (32 women and 57 men). The study group was divided into two groups - 46 (51.7%) patients were given pharmacological cardioversion with 70 mg of propafenone and 100 or 200 mg of antazoline, whereas the other 43 (48.3%) patients underwent ECV. There were no statistically significant differences between the groups regarding: left atrial area, left atrium diameter, right atrial area and right atrium diameter. In the overall population, ECV was more effective than antazoline with propafenone therapy (31 [72.1%] vs. 20 [43.5%]; p = 0.01). A similar relationship was demonstrated in patients with persistent AF (13 [59.1%] vs. 3 [12.5%]; p = 0.002). There was no significant difference in the group of patients with paroxysmal AF (18 (85.6%) vs. 17 (77.3%); p = 0.7). In AF during the cryoablation procedure ECV appears to be more effective in restoring and maintaining sinus rhythm at discharge than antazoline with propafenone in the general AF patient population, especially in patients with persistent AF.

Performance assessment of an electrostatic filter-diverter stent cerebrovascular protection device. Is it possible not to use anticoagulants in atrial fibrilation elderly patients?

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients.

Coffee consumption and adverse outcome events in patients with atrial fibrillation

Abstract Background/Introduction Moderate coffee consumption has been associated with a lower risk of major adverse cardiovascular events (MACE) in the general population. However, there are some concerns that coffee consumption might be harmful for patients with atrial fibrillation (AF). Purpose The aim of this study was to investigate the association of coffee consumption with MACE and other adverse outcome events in AF patients. Methods Data of AF patients from two large prospective, multicenter cohort studies (yearly based follow-up data from Swiss-AF and Beat-AF) were used for this analysis. Coffee consumption was assessed and categorized into two main groups "not-daily" and "daily" consumers and subcategories (<1, 1, 2-3 and ≥4cups/day). The primary endpoint was defined as a composite of stroke or systemic embolism, myocardial infarction, hospitalization for acute heart failure and cardiovascular death (MACE). We performed time-updated multivariable adjusted Cox regression analyses to investigate the association of coffee consumption with MACE and other adverse outcome events. Results Among 3,835 patients (mean age 71.4 years, 28.0% females), 3,095 (80.7%) reported daily coffee consumption. The incidence rate for MACE was 5.09 in daily and 7.49 per 100py in not-daily consumers. Cumulative incidence curves are presented in Figure 1. After comprehensive multivariable adjustment, daily coffee consumption was associated with a 23% relative risk reduction for MACE compared to not-daily consumption (hazard ratio (HR) (95% confidence interval (CI)) 0.77 (0.67-0.89), p<0.001;). Compared to patients with not-daily coffee consumption, patients with moderate coffee consumption (2-3 cups/day) had the lowest hazard for MACE (HR (95%CI) 0.73 (0.62; 0.85), p<0.001). The associations between coffee consumption and all adverse outcome events are presented in Figure 2. Conclusion In a population of AF patients, daily coffee consumption was associated with a lower risk of MACE and other adverse outcomes. These findings seem to be similar to those in the general population.

Biomarkers for the prediction of cognitive decline in atrial fibrillation patients

Abstract Background Patients with atrial fibrillation (AF) are at increased risk of cognitive decline. Biomarkers might help to identify the highest risk patients. Purpose To investigate associations of a broad panel of biomarkers with cognitive decline in a large population of AF patients. Methods We enrolled 1440 AF patients with available baseline biomarkers and cognitive testing by the Montreal Cognitive assessment (MoCA) score at inclusion and at ≥2 yearly follow-ups over three years. Cognition over time was assessed by modelling of a slope over three years. Cognitive decline was defined as a decreasing slope based on 1 standard deviation of the baseline MoCa score. We investigated the associations of biomarkers and age with cognitive decline in univariate logistic regression models by AUCs. We used Lasso modelling to build combined prediction models with biomarkers, clinical variables and both. Results Mean age was 72 years, 75% were male, 47% had paroxysmal AF and 90% were anticoagulated. During a follow-up of 3 years, cognitive decline occurred in 93 patients (6.5%). Patients with cognitive decline were older (77 vs 72 years, p=0.001), more often had paroxysmal AF (50 vs 47%, p=0.007) or a history of stroke (24 vs 11%, p=0.001), but there were no differences in anticoagulation (94 vs 90%, p=0.289). The three biomarkers with the highest univariate AUC for cognitive decline were Growth Differentiation Factor (GDF)-15 (0.67 [0.62-0.72]), Cystatin C (0.67 [0.61-0.72]) and high-sensitivity Troponin T (0.65 [0.60-0.70]), while age had the highest overall AUC (0.70 [0.64-0.75]) (Figure). The combined prediction model with the highest AUC of 0.69 (0.67-0.72) included GDF-15, age and baseline cognition. Conclusion Over 3 years, 6.5% of AF patients had cognitive decline despite a high rate of anticoagulation. Besides age, GDF-15, Cystatin C and high-sensitivity Troponin T had the highest predictive value for cognitive decline.Univariate AUCs for biomarker/ageFigure legend

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation

Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a non-pharmacological alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacological strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. A total of 3000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months post-implant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary endpoints will be evaluated at 3 years: (i) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for non-inferiority, and (ii) non-procedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant non-major bleeding) tested for superiority in the device arm against DOACs. The third primary non-inferiority endpoint is the composite of ischemic stroke and systemic embolism at 5 years. Secondary endpoints include 3- and 5-year rates of (i) ISTH-defined major bleeding and (ii) the composite of cardiovascular death, all stroke, systemic embolism, and non-procedural ISTH bleeding. This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF.

Local impedance technology for effective PVI with a novel ablation catheter: results from a large, international, multicenter registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Highly localized impedance (LI) measurements in combination with a catheter-tissue contact force (CF) during atrial fibrillation (AF) ablation may improve tissue characterization and lesion prediction during pulmonary vein isolation (PVI). Purpose This analysis explores the relationship between LI parameters, ablation spot locations and procedural success during ablation of PVs in a large population of consecutive AF patients. Methods Two-hundred twelve consecutive patients from 16 European centers undergoing de novo AF radiofrequency (RF) catheter ablation with a novel open-irrigated tip catheter enabled by CF and LI measurement capabilities (Stablepoint) were included. Ablation was guided by the magnitude and time-course of LI drop during RF delivery. The interlesion distance between each ablation spot was set ≤6 mm. First pass isolation (FPI) was defined as successful PVI at or before completion of the first encircling lesion set regardless of visual gaps. Procedural endpoint was the achievement of the PVI as assessed by entrance and exit block. Data are reported as mean±SD. Results A total of 13891 ablation spots performed around PVs were analyzed (baseline LI=161.2±19 Ω; LI drop=21.9±9 Ω; LI drop rate=3.1±2 Ω/s; RF Delivery time=9.2±4 s; CF=12.5±7 g). LI drop was predicted by baseline LI (r=0.56, 95%CI:0.55 to 0.57, p<0.0001). A total of 80 PV gaps were detected, mostly at the right pairs of the PV (63.7%, p=0.013). The FPI rate per vein was 93.3% resulting from 180 patients (84.9%) with FPI. PV gaps were located at anterior (31.3%), posterior (31%), and carina (16%) sites after the FPI evaluation. At successful ablation spots, both baseline LI and LI drop were larger than at PV gap spots (161.4Ω vs 153.0Ω, p<0.0001 for baseline LI; 22.1Ω vs 14.4Ω, p<0.0001 for LI drop), whereas RF delivery time was shorter (9.1s at successful ablation spots vs 10.1s at PV gap spots, p<0.0001). CF values seem to be higher at successful ablation spot that at PV gap spots (12.5g vs 11.4g, p=0.0592). On the basis of the receiver-operating characteristic curve (ROC) analysis, the best LI drop that predicts successful ablation spots was >20Ω (Sensitivity=56.8%, Specificity=93.2%, PPV=99.7%, Area under the ROC curve=0.7841, p<0.0001). Optimal LI drops were identified by left atrial region and were >21Ω at anterior sites and >18Ω at posterior sites. No steam pops or complications were reported during the procedures. All PVs were successfully isolated in all study patients Conclusions In a large, international population of consecutive de novo AF cases, an ablation strategy guided by LI and CF information results in a very high first pass isolation rate. LI drop is predictive of PV segment isolation. A regional approach to RF ablation guided by LI information may be useful in patients with AF.

Imaging and biophysical modelling of thrombogenic mechanisms in atrial fibrillation and stroke.

Atrial fibrillation (AF) underlies almost one third of all ischaemic strokes, with the left atrial appendage (LAA) identified as the primary thromboembolic source. Current stroke risk stratification approaches, such as the CHA2DS2-VASc score, rely mostly on clinical comorbidities, rather than thrombogenic mechanisms such as blood stasis, hypercoagulability and endothelial dysfunction-known as Virchow's triad. While detection of AF-related thrombi is possible using established cardiac imaging techniques, such as transoesophageal echocardiography, there is a growing need to reliably assess AF-patient thrombogenicity prior to thrombus formation. Over the past decade, cardiac imaging and image-based biophysical modelling have emerged as powerful tools for reproducing the mechanisms of thrombogenesis. Clinical imaging modalities such as cardiac computed tomography, magnetic resonance and echocardiographic techniques can measure blood flow velocities and identify LA fibrosis (an indicator of endothelial dysfunction), but imaging remains limited in its ability to assess blood coagulation dynamics. In-silico cardiac modelling tools-such as computational fluid dynamics for blood flow, reaction-diffusion-convection equations to mimic the coagulation cascade, and surrogate flow metrics associated with endothelial damage-have grown in prevalence and advanced mechanistic understanding of thrombogenesis. However, neither technique alone can fully elucidate thrombogenicity in AF. In future, combining cardiac imaging with in-silico modelling and integrating machine learning approaches for rapid results directly from imaging data will require development under a rigorous framework of verification and clinical validation, but may pave the way towards enhanced personalised stroke risk stratification in the growing population of AF patients. This Review will focus on the significant progress in these fields.

Abstract 14899: Ten Year Performance of Convergent Cryoballoon Hybrid Ablation With Left Atrial Appendage Exclusion in Persistent and Long Standing Persistent Atrial Fibrillation: A Trac-Af Registry Outcome Study

Introduction: Catheter ablation (CA) efficacy in persistent and long standing persistent atrial fibrillation (AF) remains poor. The Convergent procedure with endocardial cryoballoon and left atrial appendage exclusion (LAAE) addresses multiple epicardial/endocardial targets offering a comprehensive approach. We report clinical outcomes in a prospectively collected registry supplemented by continuous device monitoring in a diseased AF patient population. Methods: Single center patient data were retrospectively analyzed in the TRAC-AF registry (NCT05111015) between November 2011-November 2021. Epicardial ablations were performed by cardiothoracic surgeon and endocardial CA performed by electrophysiologist. Clinical follow up was performed at 3, 6, and 12 months and every 6 months thereafter. AF burden was determined from patients with ≥30 days of 24 hr continuous rhythm monitoring following a 90 day blanking period. Results: A total of 228 patients (69% male) received hybrid Convergent ablation. Mean age was 66 yrs, mean BMI was 30.2 ± 6.2, and in 70% of patients, CHA2DS2-VASc was ≥2. Baseline AF types were paroxysmal (7%), persistent (43%), and longstanding persistent (50%). Mean AF duration was 5.1 ± 6.2 yrs. Fifty-seven percent of patients had failed CA prior to hybrid ablation and 30.6% had LAAE with an epicardial clip. Of 228 patients, 114 (50%) had continuous rhythm monitoring. Mean residual AF burden was 5.2 ± 16.3% and of those, 77% had ≤1% mean residual AF burden, and 88% had ≤5% mean residual AF burden. A repeat CA after hybrid Convergent occurred in 23% (53/228) of patients at a mean 645.8 ± 511.4 days from the index procedure with 4.4% requiring >1; 88.5% of all repeat ablations included a mitral annular line. Conclusions: The hybrid Convergent ablation with endocardial cryoballoon and LAAE provides long term sustainable low AF burden despite rigorous endpoint surveillance in a significantly diseased AF population which includes prior failed CA patients over a decade of follow up.

Amiodarone therapy and risk of primary lung cancer; insights from a real-life contemporary population study

Abstract Background Amiodarone is the most effective antiarrhythmic therapy to maintain sinus rhythm in atrial fibrillation (AF) patients. There is a controversy regarding the association of amiodarone therapy with an increased risk of lung cancer. We aimed to assess the relationship between amiodarone treatment and primary lung cancer (PLC) incidence in a contemporary population of AF patients. Methods This is a retrospective study among patients from the Southern district of Clalit Health Services in Israel between 1st January 1999 and 1st July 2021. The study population comprised solely of patients with atrial fibrillation since this is the most prevalent condition for prescribing amiodarone. Patients treated with amiodarone were matched in a 1:1 manner with controls not exposed to amiodarone based on age, sex, living area, and atrial fibrillation diagnosis duration. To avoid immortal time bias, follow-up times of the matched controls were left adjudicated to truncate the amiodarone-free period of their matched cases. Patients with prior PLC were excluded. The primary outcome was the incidence of any PLC. We performed survival analyses using multivariable Cox regression controlling for potential confounders. Results During the study period, 7,048 patients who initiated amiodarone treatment were identified, of whom 6,449 were matched with controls. The mean age was 71.5 years, and 46.4% were women among the matched population. The amiodarone-treatment group had higher rates of smoking (30.3% vs. 26.8%), prior non-lung-related malignancy (14.9% vs. 13.5%), rheumatic disease (4.5% vs. 3.5%), diabetes (38.3% vs. 32.6%), history of myocardial infarction (316% vs. 19.6%), renal failure (17.2% vs. 10.8%) and congestive heart failure (33.8% vs. 20.7%); p<0.05 for all. During the study, with a mean follow-up time of 5.7 years, PLC occurred in 94 (1.5%) patients in the amiodarone group and 79 (1.2%) patients in the control group [adjusted-hazard-ratio (aHR) 1.10 (confidence-interval 95% (CI95%, 0.78,1.55), p=0.6]. Factors independently associated with increased PLC risk were smoking [aHR 4.25 CI95% (3.01,5.99), p<0.001], non-lung-related malignancy [aHR 1.56, CI95% (1.00,2.42), p=0.050], and peripheral vascular disease [aHR 1.77, CI95% (1.16,2.71), p=0.008] Conclusion Chronic amiodarone treatment is not associated with increased risk for PLC. Smoking and prior non-lung-related malignancy and peripheral vascular disease were independently associated with increased PLC risk, suggesting that such patients should undergo closer surveillance for early detection of PLC. Funding Acknowledgement Type of funding sources: None.

Impact of obstructive sleep apnoea on long-term atrial fibrillation-free survival after catheter ablation

Abstract Introduction Early rhythm-control therapy of atrial fibrillation (AF) (including catheter ablation) has been established as significantly lowering risk of adverse cardiovascular outcomes and improving overall survival and quality of life. Obstructive sleep apnoea (OSA) is a common but often overlooked comorbidity in patients with AF that may lead to difficulties in maintaining sinus rhythm. Data on the impacts of its treatment on recurrence remain conflicting. Objective To determine the prevalence of OSA in a population of AF patients submitted to catheter ablation and its impact on recurrence after a successful procedure. Methods Retrospective study of patients with AF consecutively submitted to catheter ablation in a tertiary centre between January 2017 and December 2020. The main outcome was AF recurrence after ablation. Sociodemographic variables and clinical data were retrieved for each patient, including type of AF, comorbidities, screening and diagnosis of OSA, treatment of OSA prior to ablation, time from ablation to recurrence of AF, method of ablation (radiofrequency or cryo). Statistical comparison between patients with and without OSA was made, including survival curves and Cox regression to determine time to recurrence and adjust for confounding variables. Results A total of 189 patients were included with a mean age of 63.49±11.09 years. Mean follow-up time after ablation was 2.76±1.56 years. Patients who recurred after ablation had undergone more electrical cardioversions prior to the procedure (1.640±1.583 vs 0.800±0.966, p 0.002), had more persistent AF (p 0.036) and had more OSA (32.7% vs 15.7%, p=0.011). There were no differences regarding age, gender, body-mass index, history of hypertension, diabetes, chronic kidney disease or heart failure, method of ablation and diagnosis of OSA prior to ablation. Forty-nine patients (18.7%) had OSA, with only 16 (32.7%) having been diagnosed before ablation. OSA was screened in only 60 cases (31.7%), mostly due to symptoms (76.1%) and not per protocol. Patients with OSA had earlier recurrence of AF after ablation (p Log-rank 0.012) with a hazard two times greater of recurrence, even after adjusting for confounding (p 0.026; hazard-ratio 2.025; confidence interval 95% 1.086–3.775). One year recurrence rate was 31% in patients with OSA (vs 15%). Regarding patients under treatment for OSA prior to ablation, there was no difference in survival (p Log-rank 0.859). Conclusion In real-world practice, OSA is still a largely underinvestigated condition that significantly impairs AF control and contributes to worse cardiovascular outcomes. Recurrence was 2 times higher in patients with OSA. No impact of treatment in time to recurrence was found. Efforts must be made to increase screening of this condition in order to improve outcomes. Further studies are needed to clarify the benefits of OSA treatment in AF recurrence. Funding Acknowledgement Type of funding sources: None.

Relationship of diabetes, heart failure, and N-terminal pro-B-type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation.

AimsWe aim to explore the relationship of heart failure (HF) and diabetes with cardiovascular (CV) death or hospitalization for HF (HHF) and to study the clinical utility of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in an unselected patient population with atrial fibrillation (AF).Methods and resultsPatients with AF admitted to a tertiary academic center between January 2005 and July 2019 were identified through a search of electronic health records. We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, coronary artery disease, hypertension, smoking, C‐reactive protein, and low‐density lipoprotein cholesterol. To select the most informative variables, we performed a least absolute shrinkage and selection operator Cox regression with 10‐fold cross‐validation. In total, 7412 patients (median age 70 years, 39.7% female) were included in this analysis and followed over a median of 4.5 years. Both diabetes [adjusted (Adj.) HR 1.87, 95% CI 1.55–2.25] and HF (Adj. HR 2.57, 95% CI 2.22–2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared with patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all‐cause death. NT‐proBNP showed good discriminatory performance (area under the curve 0.78, 95% CI 0.77–0.80) and the addition of NT‐proBNP to the covariates used for adjustment resulted in a significant area under the curve improvement (Δ = 0.04, P < 0.001). With least absolute shrinkage and selection operator, the strongest associations for CV death/HHF were obtained for NT‐proBNP [HR 1.91 per 1‐SD in log‐transformed biomarker], HF (HR 1.72), and diabetes (HR 1.56).ConclusionsDiabetes and HF were independently associated with an increased risk of CV death/HHF in an unselected AF patient population, and NT‐proBNP improved risk assessment. These findings suggest that AF patients with diabetes and/or HF should be managed not only for their risk of stroke and systemic embolic events but also for CV death/HHF.

Comparison of anticoagulation with left atrial appendage closure after atrial fibrillation ablation: Rationale and design of the OPTION randomized trial

For patients with symptomatic atrial fibrillation (AF), physicians typically offer AF ablation for symptom relief; however, patients often anticipate/expect a life free from anticoagulation. This belief puts patients at increased risk of stroke due to the potential for asymptomatic AF postablation if anticoagulation is ceased contrary to clinical guidelines. Although the WATCHMAN device has been FDA-approved to decrease the risk of thromboembolism from the left atrial appendage (LAA) in patients with an appropriate rationale to avoid oral anticoagulation, it has not been well-studied following AF ablation. Additionally, there are limited data comparing the WATCHMAN device to direct oral anticoagulants. The OPTION study will investigate whether LAA closure with the WATCHMAN FLX device is a reasonable alternative to oral anticoagulation following percutaneous catheter ablation for nonvalvular AF. OPTION is a multinational, multicenter, prospective randomized clinical trial. Patients with a CHA2DS2-VASc of ≥2 in men or ≥3 in women and who underwent a AF catheter ablation procedure between 90 and 180 days prior to randomization (sequential) or are planning to have catheter ablation within 10 days of randomization (concomitant) will be randomized in a 1:1 allocation of WATCHMAN FLX vs control. Control patients will start or continue market-approved oral anticoagulation for the duration of the trial. A total of 1600 patients were randomized from 130 global investigational sites. Follow-up for both device and control patients will occur at 3, 12, 24, and 36 months. The primary effectiveness noninferiority endpoint is stroke (ischemic or hemorrhagic), all-cause death, or systemic embolism at 36 months. The primary safety superiority endpoint is nonprocedural bleeding through 36 months (International Society on Thrombosis and Haemostasis [ISTH] major bleeding or clinically relevant nonmajor bleeding). The secondary noninferiority endpoint is ISTH major bleeding through 36 months (including procedural bleeding). This trial will assess the safety and efficacy of WATCHMAN FLX in a postablation contemporary clinical AF patient population at risk of stroke.

The characteristic of an abnormal p-wave axis in patients with atrial fibrillation

BackgroundsAn adverse increased risk of atrial fibrillation (AF) can be detected by measuring the p-wave indices, including prolonged p-wave duration, the PR interval, abnormal p-wave terminal force, and abnormal p-wave axis (aPWA). Our purpose was to characterize the AF patient population with an aPWA and to identify whether the aPWA was associated with recurrence after catheter ablation of AF. MethodsThis study retrospectively included 249 patients with AF who underwent catheter ablation in our hospital from October 2015 to May 2019. We measured the p-wave indices and left atrial cavity size (LAVI) before the catheter ablation. A logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence of AF recurrence over 12 months after the ablation. ResultsAn aPWA was observed in 35 patients (14%). There were significantly more patients with an aPWA in the non-PAF than PAF patients (26% versus 7%, p < 0.001). The patients with an aPWA had a significantly larger LAVI values (37 ± 12 versus 45 ± 11 ml/m2, p = 0.016). In a multivariate analysis, an aPWA (odds ratio, 4.27; 95% confidence interval, 1.75–10.4; p = 0.001) and the LAVI (odds ratio, 1.04; 95% confidence interval, 1.00–1.08; p = 0.032) were independently associated with recurrence after catheter ablation. ConclusionsOur results demonstrated that measuring the aPWA in patients with atrial fibrillation before ablation was useful for identifying patients at a higher risk of recurrence after catheter ablation of AF.

Anticoagulant therapy for the prevention of recurrent stroke in patients with atrial fibrillation: a comprehensive risk management

Effective secondary prevention of ischemic stroke in patients with atrial fibrillation (AF) implies long-term oral anticoagulant therapy. It has been proven that the use of direct oral anticoagulants (DOACs) is more effective, safer and more convenient for a patient than vitamin K antagonists. However, the selection of most effective and safe DOAC represented without direct comparisons in randomized controlled trials (RCTs) cannot be reliable due to the inevitable differences in the cohorts of studied patients and differences in methodological approaches. It should be noted that the population of patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) in terms of basic characteristics was as close as possible to the Russian population of AF patients compared with study populations of other DOACs. Of great importance for ensuring the overall benefit from DOACs is the possibility of comprehensive protection of the elderly patient with AF. This approach, along with the risk of recurrent stroke and possible bleeding events, takes into account other risks that can significantly worsen the prognosis and health of a patient with AF, such as the risk of coronary events, impairment of renal function, and cognitive impairment that can lead to low adherence to treatment. Rivaroxaban therapy makes it possible to simultaneously reduce the listed risks, providing comprehensive protection for an elderly patient with AF.

Renal Function Protection as an Important Component of a Comprehensive Approach to the Management of Patients with Atrial Fibrillation

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.