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Aims: Rhythm control of non-paroxysmal atrial fibrillation (AF) is significantly more challenging, as a result of arrhythmia perpetuation promoting atrial substrate changes and AF maintenance. We describe a tailored ablation strategy targeting multiple left atrial (LA) sites via a pentaspline pulsed field ablation (PFA) catheter in persistent AF sustained beyond 6 months (PerAF > 6 m) and long-standing persistent AF (LSPAF)., Methods and Results: The ablation protocol included the following stages: pulmonary vein antral and posterior wall isolation plus anterior roof line ablation (Stage 1); electrogram-guided substrate ablation (Stage 2); atrial tachyarrhythmia regionalization and ablation (Stage 3). Seventy-two [age:68 ± 10years, 61.1%males; AF history: 25 (18-45) months] patients with PerAF > 6 m (52.8%) and LSPAF (47.2%) underwent their first PFA via the FarapulseTM system. LA substrate ablation (Stage 1 and 2) led to AF termination in 95.8% of patients. AF organized into a left-sided atrial flutter (AFlu) in 46 (74.2%) patients. The PFA catheter was used to identify LA sites showing diastolic, low-voltage electrograms and entrainment from its splines was performed to confirm the pacing site was inside the AFlu circuit. Left AFlu termination was achieved in all cases via PFA delivery. Total procedural and LA dwell times were 112 ± 25 min and 59 ± 22 min, respectively. Major complications occurred in 2 (2.8%) patients. Single-procedure success rate was 74.6% after 14.9 ± 2.7 months of follow-up; AF-free survival was 89.2%., Conclusion: In our cohort, PFA-based AF substrate ablation led to AF termination in 95.8% of cases. Very favourable clinical outcomes were observed during >1 year of follow-up., Competing Interests: Conflict of interest: M.L.M. is a consultant for AtriCure. A.N. serves as a consultant for Abbott, Biosense Webster, Biotronik, Boston Scientific, and iRhythm. C.d.A. receives research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips and Acutus and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical and Daiichi Sankyo. G.B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Thermal atrial fibrillation (AF) ablation exerts an additive treatment effect on the cardiac autonomic nervous system (CANS). This effect is mainly reported during ablation of the right superior pulmonary vein (RSPV), modulating the right anterior ganglionated plexus (RAGP), which contains parasympathetic innervation to the sinoatrial node in the epicardial fat pad between RSPV and superior vena cava (SVC). However, a variable response to neuromodulation after ablation is observed, with little to no effect in some patients. Our objective was to assess clinical and anatomic predictors of thermal ablation-induced CANS changes, as assessed via variations in heart rate (HR) postablation., Methods: Consecutive paroxysmal AF patients undergoing first-time PV isolation by the cryoballoon (CB) or radiofrequency balloon (RFB) within a 12-month time frame and with preprocedural cardiac computed tomography (CT), were evaluated. Preablation and 24-h postablation electrocardiograms in sinus rhythm were collected and analyzed to assess HR. Anatomic evaluation by CT included the measurement of the shortest distance between the SVC and RSPV ostium (RSPV-SVC distance)., Results: A total of 97 patients (CB, n = 50 vs. RFB, n = 47) were included, with similar baseline characteristics between both groups. A significant HR increase postablation (ΔHR ≥ 15 bpm) occurred in a total of 37 patients (38.1%), without difference in number of patients between both thermal ablation technologies (CB, 19 [51%]), RFB, 18 [49%]). Independent predictors for increased HR were RSPV-SVC distance (odds ratio [OR]: 0.49, CI: 0.34-0.71, p value < .001), and age (OR: 0.94, CI: 0.89-0.98, p value = .003)., Conclusions: Thermal balloon-based PV isolation influences the CANS through its effect on the RAGP, especially in younger patients and patients with shorter RSPV-SVC distance., (© 2024 Wiley Periodicals LLC.)

Background: Rhythm control, either with antiarrhythmic drugs or catheter ablation, and rate control strategies are the cornerstones of atrial fibrillation (AF) management. Despite the increasing role of rhythm control over the past few years, it remains inconclusive which strategy is superior in improving clinical outcomes., Objectives: This study summarizes the total and time-varying evidence regarding the efficacy of rhythm- vs rate-control strategies in the management of AF., Methods: We systematically perused the MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases for randomized controlled trials from inception to November 2023. We included studies that compared the efficacy of rhythm control (ie, antiarrhythmic drugs classes Ia, Ic, or III, AF catheter ablation, and electrical cardioversion) and rate control (ie, beta-blocker, digitalis, or calcium antagonist) strategies among patients with nonvalvular AF. The primary outcome was cardiovascular (CV) death, whereas secondary outcomes included all-cause death, stroke, hospitalization for heart failure (HF), sinus rhythm at the end of the follow-up, and rhythm control-related adverse events. A cumulative meta-analysis to assess temporal trends and a meta-regression analysis using the percentage of ablation use was performed., Results: We identified 18 studies with a total of 17,536 patients (mean age: 68.6 ± 9.7 years, 37.9% females) and a mean follow-up of 28.5 months. Of those, 31.9% had paroxysmal AF. A rhythm control strategy reduced CV death (HR: 0.78; 95% CI: 0.62-0.96), stroke (HR: 0.801; 95% CI: 0.643-0.998), and hospitalization for HF (HR: 0.80; 95% CI: 0.69-0.94) but not all-cause death (HR: 0.86; 95% CI: 0.73-1.02) compared with a rate control strategy. This benefit was driven by contemporary studies, whereas more ablation use within the rhythm control arm was associated with improved outcomes, except stroke., Conclusions: In patients with AF, a contemporary rhythm control strategy leads to reduced CV mortality, HF events, and stroke compared with a rate control strategy., Competing Interests: Funding Support and Author Disclosures Dr Saguner has received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, BMS/Pfizer, and Medtronic; and speaker/advisory board/consulting fees from Bayer Healthcare, Biotronik, Daiichi-Sankyo, Medtronic, Novartis, Pfizer, Stride Bio Inc, and Zoll; and has stock options from Gilead Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA., Methods: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding., Results: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, P non-inferiority  < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48)., Conclusion: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Pulsed field ablation (PFA) is selective for the myocardium. However, vagal responses and reversible effects on ganglionated plexi (GP) are observed during pulmonary vein isolation (PVI). Anterior-right GP ablation has been proven to effectively prevent vagal responses during radiofrequency-based PVI., Objective: The purpose of this study was to test the hypothesis that PFA-induced transient anterior-right GP modulation when targeting the right superior pulmonary vein (RSPV) before any other pulmonary veins (PVs) may effectively prevent intraprocedural vagal responses., Methods: Eighty consecutive paroxysmal atrial fibrillation patients undergoing PVI with PFA were prospectively included. In the first 40 patients, PVI was performed first targeting the left superior pulmonary vein (LSPV-first group). In the last 40 patients, RSPV was targeted first, followed by left PVs and right inferior PV (RSPV-first group). Heart rate (HR) and extracardiac vagal stimulation (ECVS) were evaluated at baseline, during PVI, and postablation to assess GP modulation., Results: Vagal responses occurred in 31 patients (78%) in the LSPV-first group and 5 (13%) in the RSPV-first group (P <.001). Temporary pacing was needed in 14 patients (35%) in the LSPV-first group and 3 (8%) in the RSPV-first group (P = .003). RSPV isolation was associated with similar acute HR increase in the 2 groups (13 ± 11 bpm vs 15 ± 12 bpm; P = .3). No significant residual changes in HR or ECVS response were documented in both groups at the end of the procedure compared to baseline (all P >.05)., Conclusion: PVI with PFA frequently induced vagal responses when initiated from the LSPV. Nevertheless, an RSPV-first approach promoted transient HR increase and reduced vagal response occurrence., Competing Interests: Disclosures Dr Sarkozy is a consultant for Biosense Webster, Medtronic, Biotronik, and MicroPort. Dr de Asmundis received research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, AtriCure, Acutus Medical, and Daiichi Sankyo. Dr Chierchia received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend a rhythm control strategy in patients with symptomatic atrial fibrillation (AF) while catheter ablation has been shown to be a safer and more efficacious approach than antiarrhythmic medications., Methods: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. In this sub-study, we included 276 cases who had a history of AF, particularly on the rhythm strategy, and catheter ablation procedures had been performed before the index admission., Results: Among 276 AF patients (mean age: 76.4 ± 11.5 years, 58 % male), 60.9 % (N = 168) had persistent AF and 39.1 % (N = 108) had paroxysmal AF. Heart failure was the main cause of admission in 54.3 % (N = 145) of the patients, while 14.1 % (N = 39) were admitted due to paroxysmal AF, 7.3 % (N = 20) due to bradyarrhythmic reasons, and 6.5 % (N = 18) suffered from acute coronary syndrome. Most importantly, heart failure with reduced ejection fraction was present in 76 (27 %) patients. Only 10 patients out of the total (3 %, mean age 59.7 years) had undergone AF ablation while electrical cardioversion had been attempted in 37 (13.4 %) patients. Interestingly, in this AF population with heart failure, 3.6 % (N = 10) had a defibrillator implanted (4 single-chamber), and only 1.5 % (N = 4) had a cardiac resynchronization therapy defibrillator (CRT-D)., Conclusion: High prevalence of persistent AF was detected in hospitalized patients, with heart failure being the leading cause of admission and main co-morbidity. Rhythm control strategies are notably underused, along with CRT-D implantation in patients with AF and heart failure., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosures Dr Boveda consults for Medtronic, Boston Scientific, MicroPort, and ZOLL. Dr Sarkozy is a consultant for Biosense Webster, Medtronic, Biotronik, and MicroPort. Dr Battista Chierchia received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Dr de Asmundis receives research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus Medical and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, AtriCure, Acutus Medical, and Daiichi Sankyo. Dr Albenque consults for Abbott and Volta Medical. The other authors report no conflicts.

Purpose: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece., Methods: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample., Results: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%)., Conclusion: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background and Objectives : The proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess anticoagulation status and LAAC indications in patients with AF from the HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods : The HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on 3 March 2022 in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves or moderate-to-severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results : Two hundred fifty-six patients (mean age 76.6 ± 11.7, 148 males) were included in our analysis. Most of them ( n = 159; 62%) suffered from persistent AF. The mean CHA2DS2-VASc score was 4.28 ± 1.7, while the mean HAS-BLED score was 1.47 ± 0.9. Three out of three patients with a a CHA2DS2-VASc score of 0 or 1 (female) were inappropriately anticoagulated. Sixteen out of eighteen patients with a CHA2DS2-VASc score 1 or 2 (if female) received anticoagulants. Thirty-one out of two hundred thirty-five patients with a CHA2DS2-VASc score > 1 or 2 (if female) were inappropriately not anticoagulated. Relative indications for LAAC were present in 68 patients with NVAF (63 had only one risk factor and 5 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had an eGFR value < 15 mL/min/1.73 m 2 for a total of 73 risk factors. Moreover, 33 had a HAS-BLED score ≥ 3. No LAAC treatment was recorded. Conclusions : Anticoagulation status was nearly optimal in a high-thromboembolic-risk population of cardiology patients who were mainly treated using NOACs. One out of four AF patients should be screened for LAAC.

Aims: The CHA 2 DS 2 -VASc score is fundamental to stroke risk assessment in atrial fibrillation. However, stroke-related risk factors can be modified later in life. This study aimed to assess the association of changes in CHA 2 DS 2 -VASc score over time (Delta CHA 2 DS 2 -VASc score) with the risk of ischemic stroke., Materials and Methods: This is an observational analysis of 1127 atrial fibrillation patients previously enrolled in the MISOAC-AF trial. After a median 2.6-year follow-up period, baseline and follow-up CHA 2 DS 2 -VASc scores were used to extract the Delta CHA 2 DS 2 -VASc score. The stroke predicting accuracies of the baseline, follow-up, and Delta CHA 2 DS 2 -VASc scores were assessed through regression analyses., Results: The mean baseline, follow-up, and Delta CHA 2 DS 2 -VASc scores were 4.2, 4.8, and 0.6 respectively. Ischemic stroke occurred in 54 (4.4%) patients, of which 83.3% had a Delta CHA 2 DS 2 -VASc score ≥1, contrary to 40.1% of the stroke-free group. The stroke risk per 1-point increase of the CHA 2 DS 2 -VASc score was not significantly associated with the baseline score (aHR=1.14; 95%CI: 0.93-1.41; p=0.201), whereas a significant association was observed with the follow-up (aHR=2.58; 95% CI: 2.07-3.21; p<0.001) and Delta (aHR=4.56; 95%CI: 3.50-5.94; p<0.001) scores. C-index assessment indicated that follow-up and Delta CHA 2 DS 2 -VASc scores were more potent predictors of ischemic stroke compared to baseline., Conclusion: In atrial fibrillation patients, changes in CHA 2 DS 2 -VASc score over time were associated with the incidence of stroke. The improved predictability of follow-up and Delta CHA 2 DS 2 -VASc scores indicates that stroke risk is not a static parameter., Trial Registration: This is an observational, post-hoc analysis of the MISOAC-AF randomized controlled trial, registered on ClinicalTrials.gov (identifier: NCT02941978; registered: October 21, 2016)., (© 2023. The Author(s).)

Background: We performed a network meta-analysis of randomized controlled trials comparing non-vitamin K antagonist oral anticoagulant (NOAC)-based versus vitamin K antagonists (VKA)-based regimens in patients with atrial fibrillation (AF) and acute coronary syndromes or PCI, aiming to examine the precise impact of recently established antithrombotic strategies on major bleeding as primary end-point and other safety and efficacy as secondary end-points., Methods: A literature search was conducted for randomized controlled trials. Our search took place in three major databases. The primary endpoint of our study was bleeding. To combine direct and indirect evidence across trials, a frequentist network meta-analysis with a random-effects model was used., Results: Five studies were found eligible for the meta-analysis enrolling a total of 11,542 patients. Five studies (N = 4903 patients) contributed to the network. Compared to the triple antithrombotic therapy (TAT)-based VKA, only the dual antithrombotic therapy (DAT) based NOAC reduced the bleeding (RR 0.57, 95%CI 0.40-0.82). There was no statistically significant difference between DAT-based VKA (RR = 0.66, 95%CI = 0.40-1.09) or TAT-based NOAC (RR = 0.80, 95%CI = 0.43-1.49). DAT-based NOAC ranked best (P-score = 0.91), followed by DAT-based VKA (P-score = 0.67), TAT-based NOAC (P-score = 0.40), and TAT-based VKA (P-score = 0.03)., Conclusion: The network meta-analysis of four antithrombotic strategies, demonstrated that in patients with AF undergoing PCI the combination of DAT-based NOAC is associated with a significantly lower risk of major bleeding events. This strategy does not seem to be less effective in terms of prevention of ischemic events compared to the other regimens., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Aim: We conducted a systematic review and meta-analysis of randomized and observational studies with a control group to evaluate the effectiveness and safety of a time to isolation (TTI)-based strategy of cryoballoon ablation (CBA) in the treatment of atrial fibrillation (AF)., Methods: Three electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Embase) without language restrictions were searched. The intervention assessed was a TTI-based strategy of CBA in the treatment of AF. TTI was defined as the time from the start of freezing to the last recorded pulmonary veins' potential. The comparison of interest was intended conventional protocol of CBA. The primary endpoint was freedom from atrial arrhythmia., Results: Nine studies were deemed eligible (N = 2289 patients). Eight studies reported freedom from atrial arrhythmia and pooled results showed a marginally similar success rate between the two protocols (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 0.98-1.56). A prespecified subgroup analysis verified that a high dose TTI strategy (with >120 s duration of cryotherapy post-TTI) compared to the conventional protocol could significantly increase the patients without atrial arrhythmia during follow-up (OR: 1.39; 95% CI: 1.05-1.83). TTI strategy could also significantly decrease total procedure time (SMD: -26.24 min; 95% CI: -36.90 to -15.57) and phrenic nerve palsy incidence (OR: 0.49; 95% CI: 0.29-0.84)., Conclusion: Moderate confidence evidence suggests that an individualized CBA dosing strategy based on TTI and extended (>2 min post-TTI) duration of CBA is accompanied by fewer recurrences post-AF ablation., (© 2022 Wiley Periodicals LLC.)

Purpose: Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF., Methods: We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs., Results: We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87-6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19-3.05). AHREs were not associated with a statistically significant increased mortality risk., Conclusion: The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke., Registration Number (doi): Available in https://doi.org/10.17605/OSF.IO/ZRF6M ., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The objective of the present systematic review was to compare the effectiveness and safety of class Ic agents for cardioversion of paroxysmal atrial fibrillation (AF), in patients with and without structural heart disease (SHD)., Methods: We focused on RCTs enrolling at least 50 adult patients with electrocardiogram-documented paroxysmal AF that compared either two pharmacological class Ic cardioversion agents (flecainide, propafenone), regardless of study design (parallel or crossover). We searched MEDLINE and the Cochrane Central Register of Controlled Trials. Initial search was performed from inception to 15 July 2021 with no language restrictions., Results: Intravenous flecainide is the most effective option for pharmacologic cardioversion of AF since only 2 patients need to be treated in order to cardiovert one more within 4 h. Most importantly, class Ic agents appear to be safe in the context of pharmacologic cardioversion of AF irrespective of the presence of SHD, pointing towards a possible reappraisal of the role in this setting., Conclusion: We suggest that class Ic agents (with flecainide appearing to be more effective) should be used for pharmacologic cardioversion in stable AF patients presenting in emergency department with unknown medical history, after excluding severe cardiac disease through a bedside examination., Registration Number (doi): Available in https://osf.io/apwt7/ , https://doi.org/10.17605/OSF.IO/APWT7., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autonomic neuromodulation therapies (ANMTs) (ie, ganglionated plexus ablation, epicardial injections for temporary neurotoxicity, low-level vagus nerve stimulation [LL-VNS], stellate ganglion block, baroreceptor stimulation, spinal cord stimulation, and renal nerve denervation) constitute an emerging therapeutic approach for arrhythmias. Very little is known about ANMTs' preventive potential for postoperative atrial fibrillation (POAF) after cardiac surgery. The purpose of this review is to summarize and critically appraise the currently available evidence. Herein, the authors conducted a systematic review of 922 articles that yielded 7 randomized controlled trials. In the meta-analysis, ANMTs reduced POAF incidence (OR: 0.37; 95% CI: 0.25 to 0.55) and burden (mean difference [MD]: -3.51 hours; 95% CI: -6.64 to -0.38 hours), length of stay (MD: -0.82 days; 95% CI: -1.59 to -0.04 days), and interleukin-6 (MD: -79.92 pg/mL; 95% CI: -151.12 to -8.33 pg/mL), mainly attributed to LL-VNS and epicardial injections. Moving forward, these findings establish a base for future larger and comparative trials with ANMTs, to optimize and expand their use., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF., Methods: This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction., Results: In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17-2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09-2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35-4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization., Conclusion: Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis., (© 2021. The Author(s).)

Background: A bleeding episode may herald cancer in the general population. Oral anticoagulants (OACs), the mainstay treatment for atrial fibrillation (AF), are known to increase the risk of bleeding, and may thus promote an earlier diagnosis of cancer. Data regarding the association of bleeding episodes with cancer in patients with AF on OACs are scarce., Methods: In this systematic review and meta-analysis, we searched electronic databases (Medline, Scopus, and Central) and gray literature sources for studies of patients with nonvalvular AF under any OAC, from inception until 14 October 2020. The primary outcome was the association of bleeding occurrences with the detection of cancer. A subgroup analysis was performed according to OAC type [NOAC (non-vitamin K oral anticoagulant) versus VKA (vitamin K antagonist)]., Results: Overall, 4 studies were included, accounting for a total of 144,362 patients with AF receiving OAC. During follow-up, 816 (0.57%) cases of cancer were confirmed. The presence of a bleeding event, either major or minor, was associated with a higher risk for cancer detection (odds ratio [OR] 8.79, 95% confidence interval [CI] 4.98-15.51, and I 2 85%). Heterogeneity was explained after studies were stratified by the type of OAC (NOACs: OR 6.12, 95% CI 4.47-8.37, I 2 0%, VKAs: OR 15.16, 95% CI 12.61-18.23, and I 2 0%)., Conclusion: The detection of a bleeding event could be an alerting sign of cancer in patients with AF on OACs, particularly in patients receiving VKAs. REGISTRATION NUMBER (DOI): available in https://doi.org/10.17605/OSF.IO/3948R, DOI: 10.17605/OSF.IO/3948R., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2020 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Differentiated thyroid cancer (DTC) represents the most common form of thyroid neoplasms and is becoming increasingly prevalent. Evidence suggests a possible relationship between DTC diagnosis and subsequent atrial fibrillation (AF). If confirmed, this may present an alarming health risk (AF) in an otherwise condition with a relatively good prognosis (DTC). The aim of this systematic review and meta-analysis is to provide for the first time a pooled estimate of AF incidence in DTC patients in comparison to healthy controls. A detailed search in electronic databases, clinical trial registries and grey literature was performed to identify studies reporting the incidence of AF in DTC patients. Newcastle-Ottawa quality assessment scale was used to assess study quality. We used a random effects (RE) generalized linear mixed model (GLMM) in pooling of individual studies and also calculated a prediction interval for the estimate of a new study. Six observational studies met the eligibility criteria, which included totally 187,754 patients with DTC and 199,770 healthy controls. The median follow-up period was 4.3 to 18.8 years; the incidence rate of AF was 4.86 (95% CI, 3.29 to 7.17, I2 = 96%) cases per 1000 person-years, while the incidence rate ratio was 1.54 (95% CI, 1.44 to 1.65, I2 = 0%, 95% PI, 1.33 to 1.78).This is the first meta-analysis to confirm that patients with DTC are at a high risk for developing AF, which may be attributed to a state of iatrogenic hyperthyroidism due to long-term thyrotropin suppression therapy.

Purpose: We sought to indirectly compare and rank antiarrhythmic agents focusing exclusively on adults with paroxysmal atrial fibrillation in order to identify the most effective for pharmacologic cardioversion over different time settings (4 h as primary, and 12, 24 h as secondary outcomes)., Methods: We searched several databases from inception to March 2020 without language restrictions, ClinicalTrials.gov, references of reviews, and meeting abstract material. We included randomized controlled trials of patients with AF lasting ≤7 days comparing either two or more intravenous (i.v.) or oral (p.o.) pharmacologic cardioversion agents or an agent against placebo. For each outcome, we performed network meta-analysis based on the frequentist approach., Results: Forty-one trials (6013 patients) were included in our systematic review. Moderate confidence evidence suggests that i.v. vernakalant and flecainide have the highest conversion rate within 4 h, possibly allowing discharge from the emergency department and reducing hospital admissions. Intravenous and p.o. formulations of class IC antiarrhythmics (flecainide more so than propafenone) are superior regarding conversion rates within 12 h, while amiodarone efficacy is exhibited in a delayed fashion (within 24 h), especially if ranolazine is added., Conclusion: Our network meta-analysis identified with sufficient power and consistency the most effective antiarrhythmics for pharmacologic cardioversion over different time settings, with vernakalant and flecainide exhibiting a safer and more efficacious profile toward faster cardioversion.

Identifying patients at high risk of atrial fibrillation (AF) recurrence remains challenging. This study aimed to evaluate total atrial conduction time (TACT) and left atrial (LA) asynchrony as predictors of AF recurrence. Consecutive patients after the first AF episode, terminated either spontaneously or with cardioversion, underwent transthoracic echocardiography. TACT, estimated by the time delay between the onset of P-wave and the peak A'-wave on the Tissue Doppler Imaging (PA-TDI duration), atrial volumetric and functional parameters, and biatrial strain were assessed. We calculated mean PA-TDI-the average of PA-TDI measurements in all left atrial (LA) walls-and the difference between the longest and the shortest PA interval (DLS) and the standard deviation of 4 PA intervals (SD4) to assess the LA global remodeling and asynchrony, respectively. The primary endpoint was AF recurrence. Patients with recurrent AF had significantly prolonged PA-TDI intervals in each LA wall-and thus mean PA-TDI-than those without recurrence (mean PA-TDI: 157.4 ± 17.9 vs. 110.2 ± 7.7 ms, p < 0.001). At univariate analysis, LA maximum volume index, total LA emptying fraction, right atrial maximum volume index, PA-TDI, DLS, and SD4 were predictors of AF recurrence. At multivariable analysis, PA-TDI intervals in all LA walls remained strong predictors with mean PA-TDI (odds ratio 1.04; 95% confidence interval 1.03-1.06) having an optimal cutoff of 125.8 ms in receiver operator characteristics curve analysis providing 98% sensitivity and 100% specificity for AF recurrence (area under the curve = 0.989). PA-TDI was an independent predictor of AF recurrence and outperformed established echocardiographic parameters.

Background: Atrial Fibrillation (AF) has become a major global health concern and is associated with an increased risk of poor outcomes. Identifying risk factors in patients with AF can be challenging, given the high burden of comorbidities in these patients. Risk stratification schemes appear to facilitate accurate prediction of outcomes and assist therapeutic management decisions., Objective: To summarize current evidence on risk stratification scores for patients with AF., Results: Traditional risk models rely heavily on demographics and comorbidities, while newer tools have been gradually focusing on novel biomarkers and diagnostic imaging to facilitate more personalized risk assessment. Several studies have been conducted to compare existing risk schemes and identify specific patient populations in which the prognostic ability of each scheme excels. However, current guidelines do not appear to encourage the implementation of risk models in clinical practice, as they have not incorporated new ones in their recommendations for the management of patients with AF for almost a decade., Conclusion: Further work is warranted to analyze new reliable risk stratification schemes and optimally implement them into routine clinical life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA., Methods and Analysis: PReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a 'real-world' setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria., Ethics and Dissemination: The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals., Trial Registration Number: NCT03854149; Pre-results., Competing Interests: Competing interests: GG and HK have received grants and/or personal fees from Pfizer., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) including the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for patients with atrial fibrillation (AF)., Design: Network meta-analysis. Two authors independently extracted data. All authors evaluated overall confidence in the evidence., Results: Eighteen RCTs included in our review, a total of 78,796 patients with AF, with sample sizes from 90 to 21,105 patients. Apixaban 5 mg (OR: 0.79, 95% CI: 0.66 to 0.95), dabigatran 110 mg (0.91, 0.74-1.12), dabigatran 150 mg (0.66, 0.53-0.82), edoxaban 60 mg (0.87, 0.74-1.02), and rivaroxaban 20 mg (0.88, 0.74-1.03) reduced the risk of stroke or systemic embolism compared with warfarin. Dabigatran 150 mg had the highest P-score for reducing stroke or systemic embolic events. The risk of haemorhagic stroke and all-cause mortality was lower with all NOACs than with warfarin. Apixaban 5 mg (0.69, 0.60-0.80), dabigatran 110 mg (0.80, 0.69-0.93), dabigatran 150 mg (0.93, 0.80-1.08), edoxaban 30 mg (0.46, 0.40-0.54), and edoxaban 60 mg (0.78, 0.69-0.90) reduced the risk of major bleeding compared with warfarin. Edoxaban 30 mg had the highest P-score for reducing major bleeding. The plots of P-scores rank showed that apixaban offered the most favorable balance of efficacy and safety., Conclusions: This study adds an attempt for treatment ranking of both efficacy and safety outcomes. Future trials comparing directly NOACs are needed in order to provide conclusive proofs for these results and not only circumstantial evidence offered by a network meta-analysis.

Aims: The CHA2DS2-VASc score is fundamental to stroke risk assessment in atrial fibrillation. However, stroke-related risk factors can be modified later in life. This study aimed to assess the association of changes in CHA2DS2-VASc score over time (Delta CHA2DS2-VASc score) with the risk of ischemic stroke. Materials and methods: This is an observational analysis of 1127 atrial fibrillation patients previously enrolled in the MISOAC-AF trial. After a median 2.6-year follow-up period, baseline and follow-up CHA2DS2-VASc scores were used to extract the Delta CHA2DS2-VASc score. The stroke predicting accuracies of the baseline, follow-up, and Delta CHA2DS2-VASc scores were assessed through regression analyses. Results: The mean baseline, follow-up, and Delta CHA2DS2-VASc scores were 4.2, 4.8, and 0.6 respectively. Ischemic stroke occurred in 54 (4.4%) patients, of which 83.3% had a Delta CHA2DS2-VASc score ≥1, contrary to 40.1% of the stroke-free group. The stroke risk per 1-point increase of the CHA2DS2-VASc score was not significantly associated with the baseline score (aHR=1.14; 95%CI: 0.93-1.41; p=0.201), whereas a significant association was observed with the follow-up (aHR=2.58; 95% CI: 2.07-3.21; p<0.001) and Delta (aHR=4.56; 95%CI: 3.50-5.94; p<0.001) scores. C-index assessment indicated that follow-up and Delta CHA2DS2-VASc scores were more potent predictors of ischemic stroke compared to baseline. Conclusion: In atrial fibrillation patients, changes in CHA2DS2-VASc score over time were associated with the incidence of stroke. The improved predictability of follow-up and Delta CHA2DS2-VASc scores indicates that stroke risk is not a static parameter. Trial registration: This is an observational, post-hoc analysis of the MISOAC-AF randomized controlled trial, registered on ClinicalTrials.gov (identifier: NCT02941978; registered: October 21, 2016). [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to provide data on implantable loop recorder (ILR)-based atrial fibrillation (AF) rates, recurrent stroke rates, and predictors of AF in patients with cryptogenic stroke (CS) after 1, 6, 12, 24, and 36 months of follow-up. Methods: We searched MEDLINE/PubMed, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and reference lists of retrieved reports, which were published by April 30, 2023, which was the date of our last search. We utilized random-effects meta-analysis for detection rates, and meta-regression analysis, t-test (for normally distributed variables), and Mann-Whitney (for skewed variables) for predictor factors. Results: Thirteen studies were analyzed, which included data from 3,377 patients with CS or embolic stroke of undetermined source. The ILR-based AF rates in patients with CS were 4.73% (95% confidence interval [CI] 3.91–5.71) at 1 month, 13.45% (95% CI 12.19–14.81) at 6 months, 17.5% (95% CI 16.25–18.82) at 12 months, 20.69% (95% CI 19–22.49) at 24 months, and 25.98% (95% CI 23.21–28.58) at 36 months. Age and CHA2DS2-VASc score were positively associated with AF detection. Specifically, the mean difference of age and CHA2DS2-VASc score in the group with AF versus the group without AF was 7.47 (95% CI 4.58–10.36, P < 0.001) and 0.75 (95% CI 0.22–1.28, P = 0.01), respectively. Finally, AF detection was positively associated with recurrent strokes with an estimated risk ratio of 1.27 (95% CI 0.69–2.31). Conclusions: There is a correlation between AF detection rate and ILR monitoring duration. One out of eight patients was diagnosed with AF after 6 months of follow-up and about one quarter after 3 years. Our results demonstrate the critical use of ILRs, especially in older patients, and in patients with high CHA2DS2-VASc scores. [ABSTRACT FROM AUTHOR]

Pharmacologic cardioversion is a well-established alternative to electric cardioversion for hemodynamically stable patients, as it skips the risks associated with anesthesia. A recent network meta-analysis identifies the most effective antiarrhythmics for pharmacologic cardioversion with flecainide exhibiting a more efficacious and safer profile towards faster cardioversion. Moreover, the meta-analysis of class Ic antiarrhythmics revealed an absence of adverse events when used for pharmacologic cardioversion of AF in the ED, including patients with structural heart disease. The primary goals of this clinical trial are to prove the superiority of flecainide over amiodarone in the successful cardioversion of paroxysmal atrial fibrillation in the Emergency Department and to prove that the safety of flecainide is non-inferior to amiodarone in patients with coronary artery disease without residual ischemia, and an ejection fraction over 35%. The secondary goals of this study are to prove the superiority of flecainide over amiodarone in the reduction in hospitalizations from the Emergency Department due to atrial fibrillation in the time taken to achieve cardioversion, and in the reduction in the need to conduct electrical cardioversion. [ABSTRACT FROM AUTHOR]