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The article discusses a trial in which a new disease management program is implemented to improve the outcome of patients with atrial fibrillation (AF).

Aim Differential drug treatment guided by the underlying heart disease may improve outcome of rhythm control therapy. In the present study we investigated in a well-defined group with either lone atrial fibrillation (AF) or hypertension whether there were differences in rhythm control outcome between both groups in relation to the use of cardiovascular drugs. Methods and results One hundred sixty-two patients were included after successful cardioversion of persistent AF. None of the patients was given a class I or III antiarrhythmic drug. Patients' heart rhythm was checked 3 times a day, using transtelephonic monitoring for 1 month after cardioversion. One month after cardioversion up to 68% of patients had a recurrence of persistent AF. During the first 3 days almost no recurrences were seen on beta-blocker therapy whereas recurrences peaked on day 2–3 in the absence of beta-blockers. Univariate analysis showed that the use of beta-adrenergic receptor blockers and the presence of hypertension were associated with a lower recurrence rate at 1 month. Multivariate logistic regression analysis demonstrated that beta-blockade was the only statistically significant parameter predicting sinus rhythm at 1 month (OR 0.40, 95% CI 0.19–0.86, P=0.02). Conclusions Compared with lone AF patients, patients in the setting of hypertension maintain sinus rhythm much better after cardioversion when treated with a beta-blocker. Beta-blockade protects, in particular, against the early subacute recurrences. These findings underscore the importance of a differential approach towards drug prevention of post-cardioversion recurrences depending on the underlying heart disease. [ABSTRACT FROM PUBLISHER]

Introduction: Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV). The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV. Methods and Results: Ninety-seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given. Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF. Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively. Conclusion: Stand-alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) leads to a loss of atrial contraction within hours to days. During persistence of AF, cellular dedifferentiation and hypertrophy occur, eventually resulting in degenerative changes and cell death. Abnormalities in the calcium handling in response to tachycardia-induced intracellular calcium overload play a pivotal role in these processes. Methods and Results: The purpose was to investigate the mRNA expression of proteins and ion channels influencing the calcium handling in patients with persistent AF. Right atrial appendages were obtained from 18 matched controls in sinus rhythm (group 1) and 18 patients with persistent AF undergoing elective cardiac surgery. Previous duration of AF was ≤ 6 months in 9 (group 2) and > 6 months in 9 patients (group 3). In a single semiquantitative polymerase chain reaction, the mRNA of interest and of glyceraldehyde-3-phosphate dehydrogenase, were coamplified and separated by gel electrophoresis. L-type calcium channel at subunit mRNA content was inversely related to the duration of AF: -26% in group 2 compared to group 1 (P = 0.2), and -49% in group 3 compared to group 1 (P = 0.01). Inhibitory guanine nucleotide binding protein iα2 mRNA content was reduced in group 3 compared to group 1 (-30%, P = 0.01). Sarcoplasmic reticulum calcium ATPase, phospholamban and sodium-calcium exchanger mRNA contents were not affected by AF. Conclusions: AF-induced alterations in mRNA contents of proteins and ion channels involved in the calcium handling seem to occur in relation to the previous duration of AF. In the present patient population, these changes were significant only if AF lasted > 6 months. [ABSTRACT FROM AUTHOR]

Objective: Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. Methods: Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (>8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox’s MAZE surgery (n=12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. Results: L-type calcium channel α1 and sarcoplasmic reticulum Ca2+-ATPase mRNA (−57%, p=0.01 and −28%, p=0.04, respectively) and protein contents (−43%, p=0.02 and −28%, p=0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. Conclusions: Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF. [ABSTRACT FROM PUBLISHER]

Background: Preventing high heart rates in patients with atrial fibrillation (AF) is a key objective of AF management. Data regarding heart rates in patients with paroxysmal AF (PAF) is lacking. This analysis aimed to provide insight into heart rates during PAF episodes measured with continuous implantable loop monitoring., Methods: In present analysis of the Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilization in the Progression of AF study, we included 349 patients with at least one year of continuous rhythm monitoring and an episode of AF. Mean heart rates and duration of AF episodes were used to calculate total AF duration and AF duration above different heart rate cut-offs., Results: The median age was 64.0 (58.4 to 70.5) years, 152 (44%) were women and CHA 2 DS 2 -VASc score ≥2 or higher in 255 (73%) patients. During 28.3 (21.3 to 35.0) months of follow-up, the median number of AF episodes was 62 (12 to 293) with a median total AF duration of 4.6 (0.8 to 26.8) days. At baseline, 172 (49%) patients used beta-blockers, 64 (18%) used diltiazem or verapamil and 5 (1%) used digoxin. A total of 133 patients (38%) experienced a heart rate >110 bpm for more than 50% of the time during AF. Fifty-six (16%) patients had a heart rate >130 bpm for more than 50% of the time while in AF. During follow-up, 39 patients (11%) received an increase of rate-controlling medication., Conclusion: Continuous rhythm monitoring revealed that more than a third of PAF patients had heart rates above 110 bpm for more than half of their time in AF., Trial Registration Number: Clinicaltrials.gov identifier NCT02726698., Competing Interests: Competing interests: RGT reports grants from Medtronic and Abbott, and personal fees from Boehringer Ingelheim, Bayer and Pfizer/Bristol Myers Squibb all outside submitted work. RGT is coinventor of the MyDiagnostick, not receiving royalties for the past 5 years. MDM is a Medtronic employee and WP Coordinator in the H2020 ITN My-Atria (No: 766082). The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Long-term endurance exercise is suspect to elevate the risk of atrial fibrillation (AF), but little is known about cardiovascular outcome and disease progression in this subgroup of AF patients. We investigated whether previous exercise level determines cardiovascular outcome., Methods: In this post hoc analysis of the RACE 4 randomized trial, we analyzed all patients with a completed questionnaire on sports participation. Three subgroups were made based on lifetime sports hours up to randomization and previous compliance to the international physical activity guidelines. High lifetime hours of high dynamic activity patients were defined as more than 150 min·wk -1 of high-intensity physical exercise. The primary endpoint was a composite of cardiovascular death and hospital admissions., Results: A total of 879 patients were analyzed, divided in 203 high lifetime hours of high dynamic activity, 192 high lifetime hours of activity, and 484 low lifetime hours of activity patients. Over a mean follow-up of 36 months (±14), the primary endpoint occurred in 61 out of 203 (30%) high lifetime hours of high dynamic activity, 53 out of 192 (27%) high lifetime hours of activity, and 135 out of 484 (28%) low lifetime hours of activity patients ( P = 0.74). During follow-up, 42 high lifetime hours of high dynamic activity (35%), 43 high lifetime hours of activity (32%), and 104 low lifetime hours of activity patients (34%) with paroxysmal AF received electrical or chemical cardioversion or atrial ablation ( P = 0.90)., Conclusions: In patients included in the RACE 4, there seems to be no relation between previous activity levels and cardiovascular outcome and the need for electrical or chemical cardioversion or atrial ablation. Cardiovascular outcome was driven by AF-related arrhythmic events., (Copyright © 2024 by the American College of Sports Medicine.)

Background: We aimed to evaluate the association between atrial fibrillation (AF) burden, duration and number of episodes with healthcare utilisation and quality of life in patients with early paroxysmal AF without a history of AF., Methods: In this observational cohort study, we included 417 patients with paroxysmal AF from the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V) Study. Patients were monitored with an insertable cardiac monitor for 1 year. Outcomes collected were healthcare utilisation, and quality of life assessed using the Atrial Fibrillation Severity Scale and EuroQol EQ-5D-5L questionnaires., Results: During 1 year of follow-up, 63 973 AF episodes were detected in 353 (85%) patients. The median AF burden was 0.7% (IQR 0.1-4.0%). AF ablation was performed more frequently in patients with intermediate-to-high AF burdens (>0.2%) (16.2% vs 5.9%, p=0.01) and longer AF episode duration (>1 hour) (15.8% vs 2.0%, p=0.01), whereas cardioversions were more frequent in patients with longer episode duration (>1 hour) (9.5% vs 0%, p=0.04) and intermediate (0.2-1.9%) (but not high) AF burdens (13.6% vs 4.2%, p=0.01). Patients with many episodes (>147) reported higher symptom severity (p=0.001). No differences in symptom severity nor in EQ-5D-5L scores according to AF burden or duration were observed., Conclusion: In patients with early paroxysmal AF, higher AF burden and longer episode duration were associated with increased rates of healthcare utilisation but not with symptoms and quality of life. Patients with a higher number of episodes experienced more severe symptoms., Trial Registration Number: NCT02726698., Competing Interests: Competing interests: MHJPF received consulting fees from Medtronic outside this work. MBK received speaker’s honoraria from Abbott outside this work. JCN was supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658). MR received consultancy fees from Bayer and InCarda Therapeutics (to the institution). MDM is an employee of Medtronic Bakken Research Center. RGT reports grants and personal fees from Medtronic and grants from St Jude Medical outside this work. In addition, RGT has a patent as co-inventor of the MyDiagnostick issued. The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sex differences in atrial fibrillation (AF) are observed in terms of comorbidities, symptoms, therapies received, AF progression and cardiovascular complications., Methods: We assessed the differences in prevalence and the determinants of AF progression, as well as the clinical characteristics and quality of life (QoL), between women and men with paroxysmal AF included in the RACE V (Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF) study. At baseline, extensive phenotyping was done. To assess AF progression, implantable loop recorder (ILR) monitoring was used throughout follow-up. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of paroxysmal AF (>3% burden increase)., Results: 417 patients were included, 179 (43%) of whom were women. Women were older (median 67 years vs 63 years, p<0.001), less often had coronary artery disease (n=11 (6%) vs n=36 (16%), p=0.003), had more obesity (n=57 (32%) vs n=50 (21%), p=0.013), had less epicardial and pericardial fat (median 144 (interquartile range [IQR] 94-191) mL vs 199 (IQR 146-248) mL, p<0.001; and median 89 (ICQ 61-121) mL vs 105 (IQR 83-133) mL, p<0.001, respectively) and had more impaired left atrial function. The median follow-up was 2.2 (1.6-2.8) years. 51 of 417 patients (5.5% per year) showed AF progression (15/179 (8.4%) women and 36/238 (15.1%) men, p=0.032). Multivariable analysis showed tissue factor pathway inhibitor, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and PR interval being associated with AF progression in women and factor XIIa:C1 esterase, NT-proBNP and proprotein convertase subtilisin/kexin type 9 in men. QoL was not different between sexes., Conclusion: Despite older age, the incidence of AF progression was lower in women. Parameters associated with AF progression varied in part between sexes, suggesting different underlying pathophysiological mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate heart rate differences between non-dihydropyridine calcium channel blockers and beta-blockers in patients with non-permanent atrial fibrillation (AF)., Methods: Using data from 'A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation' (AFFIRM), where patients were randomised 1:1 rate or rhythm control, we compared the effect of rate control drugs on heart rate during AF as well as during sinus rhythm. Multivariable logistic regression was used to adjust for baseline characteristics., Results: A total of 4060 patients were enrolled in the AFFIRM trial, mean age was 70±9 years, 39% were women. Out of the total, 1112 patients were in sinus rhythm at baseline and used either non-dihydropyridine channel blockers or beta-blockers. Of them, 474 had AF during follow-up while remaining on the same rate control drugs, 218 (46%) on calcium channel blockers and 256 (54%) on beta-blockers. Mean age of calcium channel blocker patients was 70±8 years and 68±8 for beta-blocker patients (p=0.003), 42% were women. A resting heart rate <110 beats per min during AF was achieved in 92% of patients using calcium channel blockers and 92% of patients using beta-blockers (p=1.00). Bradycardia during sinus rhythm occurred in 17% of patients using calcium channel blockers vs 32% using beta-blockers (p<0.001). After adjusting for patient characteristics, calcium channel blockers were associated with a reduction in bradycardia during sinus rhythm (OR 0.41, 95% CI 0.19 to 0.90)., Conclusion: In patients with non-permanent AF, calcium channel blockers instituted for rate control were associated with less bradycardia during sinus rhythm compared with beta-blockers., Competing Interests: Competing interests: TK, ICVG and HJGMC have nothing to declare in relation to this paper. RGT reports grants from Medtronic and Abbott, and personal fees from Boehringer Ingelheim, Bayer and Pfizer/Bristol Meyer Squibb and is co-inventor of the MyDiagnostick, not receiving royalties for the past 5 years all outside the submitted work. MR reports consultancy fees from Bayer, Microport, InCarda Therapeutics to the institution all outside the submitted work., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF)., Methods: In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians., Results: Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHA 2 DS 2 -VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias., Conclusions: In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF., Trial Registration Number: NCT02726698., Competing Interests: Competing interests: MHJPF received speakers’ honorarium from Medtronic outside submitted work. RGT reports grants from Medtronic and Abbott, and personal fees from Boehringer Ingelheim, Bayer and Pfizer/Bristol Myers Squibb all outside submitted work. RGT is coinventor of the MyDiagnostick, not receiving royalties for the past 5 years. MDM is a Medtronic employee and WP Coordinator in the H2020 ITN My-Atria (No: 766082). IVG and AHM serve on the editorial board of BMJ Heart. The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands., Methods and Results: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented., Conclusion: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

For the diagnosis of atrial fibrillation, it is mandatory to make an ECG during the arrhythmia. In patients with paroxysmal atrial fibrillation this can be challenging. Consumer wearables such as smart watches with automated AF detection can be helpful for diagnosing even asymptomatic AF, as long as they offer the possibility to record a one lead ECG rhythm strip. Once AF is diagnosed, therapeutic decisions, such as rate-control versus rhythm-control and start of oral anticoagulation therapy need to be made on an individual basis in each patient. The present manuscript deals with frequently asked questions encountered in daily practice of treating patients with AF.

Background: Atrial fibrillation (AF) is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and has a negative impact on outcome. Reliable data on prevalence, incidence, and detection of AF from contemporary, prospective HFmrEF/HFpEF studies are scarce., Methods: This was a prespecified sub-analysis from a prospective, multicenter study. Patients with HFmrEF/HFpEF underwent 12-lead electrocardiography (ECG), 24 h Holter monitoring, and received an implantable loop recorder (ILR) at the study start. During the 2 year follow-up, rhythm monitoring was performed via ILR, yearly ECG, and two yearly 24 h Holter monitors., Results: A total of 113 patients were included (mean age 73 ± 8 years, 75% HFpEF). At baseline, 70 patients (62%) had a diagnosis of AF: 21 paroxysmal, 18 persistent, and 31 permanent AF. At study start, 45 patients were in AF. Of the 43 patients without a history of AF, 19 developed incident AF during a median follow-up of 23 [15-25] months (44%; incidence rate 27.1 (95% confidence interval 16.3-42.4) per 100 person-years). Thus, after the 2-year follow-up, 89 patients (79%) had a diagnosis of AF. In 11/19 incident AF cases (i.e., 58%), AF was solely detected on the ILR. Yearly 12-lead ECG detected six incident AF cases and four of these cases were also detected on two yearly 24 h Holter monitors. Two incident AF cases were detected on an unplanned ECG/Holter., Conclusions: Atrial fibrillation is extremely common in heart failure with HFmrEF/HFpEF and may inform on symptom evaluation and treatment options. AF screening with an ILR had a much higher diagnostic yield than conventional modalities.

Aims: Atrial fibrillation (AF) progression is associated with adverse outcome, but the role of the circadian or diurnal pattern of AF onset remains unclear. We aim to assess the association between the time of onset of AF episodes with the clinical phenotype and AF progression in patients with self-terminating AF., Methods and Results: The Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodelling, and Vascular Destabilization in the Progression of AF study included patients with self-terminating AF who underwent extensive phenotyping at baseline and continuous rhythm monitoring with an implantable loop recorder (ILR). In this subanalysis, ILR data were used to assess the development of AF progression and the diurnal pattern of AF onset: predominant (>80%) nocturnal AF, predominant daytime AF, or mixed AF without a predominant diurnal AF pattern. The median follow-up was 2.2 (1.6-2.8) years. The median age was 66 (59-71) years, and 117 (42%) were women. Predominant nocturnal (n = 40) and daytime (n = 43) AF onset patients had less comorbidities compared to that of mixed (n = 195) AF patients (median 2 vs. 2 vs. 3, respectively, P = 0.012). Diabetes was more common in the mixed group (12% vs. 5% vs. 0%, respectively, P = 0.031), whilst obesity was more frequent in the nocturnal group (38% vs. 12% vs. 27%, respectively, P = 0.028). Progression rates in the nocturnal vs. daytime vs. mixed groups were 5% vs. 5% vs. 24%, respectively (P = 0.013 nocturnal vs. mixed and P = 0.008 daytime vs. mixed group, respectively)., Conclusion: In self-terminating AF, patients with either predominant nocturnal or daytime onset of AF episodes had less associated comorbidities and less AF progression compared to that of patients with mixed onset of AF., Clinical Trial Registration: NCT02726698., Competing Interests: Conflict of interest: R.G.T. reports grants and personal fees from Boehringer Ingelheim, personal fees from Bristol Myers Squibb/Pfizer, personal fees from Bayer, grants from Medtronic, and grants from St. Jude Medical, outside the submitted work. In addition, R.G.T. has a patent as a co-inventor of the MyDiagnostick issued. M.E.H.W. reports personal fees from Medtronic, outside the submitted work. M.D.M. reports he is an employee of Medtronic. U.S. reports grants from Dutch Heart Foundation, during the conduct of the study, personal fees from Johnson & Johnson, grants from Roche, grants from EP solutions, and other from YourRhythmics BV, outside the submitted work. In addition, U.S. has a patent non-invasive classification of AF issued. Prof. H.J.G.M.C. reports a grant to support the present work, from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014–9: Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodelling, and Vascular Destabilization in the Progression of AF (RACE V). All other authors have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF., Methods and Results: We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 [interquartile range (IQR) 58-71] years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA2DS2-VASc (the CHA2DS2-VASc score assesses thromboembolic risk. C, congestive heart failure/left ventricular dysfunction; H, hypertension; A2, age ≥ 75 years; D, diabetes mellitus; S2, stroke/transient ischaemic attack/systemic embolism; V, vascular disease; A, age 65-74 years; Sc, sex category (female sex)) score was 2 (IQR 2-3), and median follow-up was 2.1 (1.5-2.6) years. The average score of the 4S-AF scheme was 4.6 ± 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression [odds ratio (OR) 1.1 95% CI 0.88-1.41, C-statistic 0.53]. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severity, only including stroke risk, severity of AF burden and substrate of AF) scheme, predicted the risk of progression (OR 1.59 95% CI 1.15-2.27, C-statistic 0.62) even after adjusting for sex and age., Conclusions: In self-terminating AF patients, the 4S-AF scheme does not predict AF progression. The 3S-AF scheme, excluding the symptom domain, may be a more appropriate score to predict AF progression., Trial Registration Numbers: Clinicaltrials.gov NCT02726698 for RACE V., Competing Interests: Conflict of interest: H.T.C. has received research support from Bayer and Pfizer and is consultant for Alveron and shareholder with Coagulation profile., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Pulmonary vein isolation (PVI) is widely accepted as an effective and safe treatment for symptomatic atrial fibrillation (AF). However, data on sex-related differences and associations with clinical outcome and safety of PVI with cryoballoon ablation are limited. We sought to compare sexrelated efficacy and safety of cryoballoon ablation and identify sex-related associations with clinical outcomes., Methods and Results: We included 650 consecutive patients with AF undergoing PVI with cryoballoon ablation at our institution between 2013 and 2017. The efficacy outcome was the first documented recurrence (&gt;30 s) of AF, atrial flutter or atrial tachycardia (AF/AT) or repeat ablation during follow-up, after a 90-day blanking period. The safety outcome was the incidence of periprocedural complications. Mean age of the population was 58±10, and 210 (32.3%) patients were women. Women were older, had a higher body mass index, had more renal dysfunction and less coronary artery disease as compared with men. The rate of AF/AT recurrence was similar between women and men at 12-month follow-up (27.6% vs 24.8%, p=0.445). The incidence of periprocedural complications was higher in women (12.9% vs 4.6%; p&lt;0.001), specifically groin haematomas and phrenic nerve palsy. On multivariate analysis, left atrial volume index (adjusted OR 1.05, 95% CI 1.00 to 1.10; p=0.032) was associated with the incidence of procedural complications in women. For men, no relation with complications could be found., Conclusion: The efficacy of cryoballoon ablation was similar between women and men; however, women had a higher risk of procedural complications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pulsed field ablation (PFA) was recently introduced for the treatment of symptomatic atrial fibrillation (AF) with the claim of selectively ablating the myocardium while sparing surrounding tissues. We present our initial experience with a PFA catheter for pulmonary vein isolation (PVI) and describe procedural findings and peri-procedural safety of the first 100 patients., Materials and Methods: We investigated 100 patients treated for symptomatic AF using the FARAWAVE PFA catheter (Farapulse, Menlo Park, CA, USA) between July 2021 and March 2022. Procedure workflow and electrophysiological findings at the time of ablation, peri-procedural complications, and operator learning curves are described., Results: The mean age of patients was 62.9 ± 9.4 years, 62% were male subjects and 80% had paroxysmal AF. The median CHA 2 DS 2 -VASc score was 1.5 (IQR: 1.0-2.0) and the mean left atrial volume index was 35.7 ± 9.6 ml/m2. In 88 (88%) patients, PVI alone was performed and in 12 (12%) patients additional ablation of the posterior wall was performed. 3D-electroanatomic mapping was performed in 18 (18%) patients. Procedures without mapping lasted for 52.3 ± 16.6 min. The mean number of applications per pulmonary vein (PV) was 8.1 ± 0.6. In all patients (100%), all PVs were confirmed to be isolated. The learning curves of the two operators who performed > 20 procedures showed a negligible variation of performance over time and practice did not significantly predict procedure time [Operator 1 (senior): R 2 = 0.034, p = 0.35; Operator 2 (junior): R 2 = 0.004, p = 0.73]. There was no difference between the procedure times between senior and junior operators (Operator 1: 46.9 ± 9.7 min vs. Operator 2: 45.9 ± 9.9 min; p = 0.73). The only complications observed were two cases of bleeding at the site of percutaneous access., Conclusion: Our initial experience shows that use of the PFA catheter for pulmonary vein isolation (PVI) is safe, fast, and easy to learn., Competing Interests: Author HG received a speaker fee from Biosense Webster. Author YB received research grants (to department) from AtriCure and Medtronic, and a speaker fee from AtriCure and Circle. He was also a proctor for Abbott, Biosense Webster, and Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Magni, Mulder, Groenveld, Wiesfeld, Tieleman, Cox, Van Gelder, Smilde, Tan, Rienstra and Blaauw.)

Objective: Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF., Methods: In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression., Results: Mean age was 65 (58-71) years, 179 (43%) were female. Follow-up was 2.2 (1.6-2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression., Conclusion: In patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed., Trial Registration Number: NCT02726698., Competing Interests: Competing interests: US reports grants from Roche Diagnostics, EP Solutions, Dutch Heart Foundation, European Union, personal fees from Roche Diagnostics, EP Solutions, other from YourRhythmics BV, outside the submitted work. In addition, US has a patent Noninvasive classification of AF licensed to YourRhythmics. JDeG reports grants and personal fees from Atricure, Bayer, Daiichi Sankyo, Johnson&Johnson, grants from Boston Scientific, personal fees from Novartis and Servier, outside the submitted work. JL reports consultancy agreement Medtronic. HTC reports grants from Bayer and Pfizer and consultancy agreements for Pfizer, Alveron, STAGO, Leo Pharma, Daiichi Sankyo, Gilead/Galapagos, Portola/Aexia and Coagulation Profile. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Aims: The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years., Methods and Results: Patients with early persistent AF and mild-to-moderate stable HF were randomized to targeted or conventional therapy. Both groups received rhythm control therapy according to guidelines. The targeted group additionally received four therapies: angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ARBs), statins, mineralocorticoid receptor antagonists (MRAs), and cardiac rehabilitation. The presence of sinus rhythm and cardiovascular morbidity and mortality at 5-year follow-up were assessed. Two hundred and sixteen patients consented for long-term follow-up, 107 were randomized to targeted and 109 to conventional therapy. At 5 years, MRAs [76 (74%) vs. 10 (9%) patients, P < 0.001] and statins [81 (79%) vs. 59 (55%), P < 0.001] were used more in the targeted than conventional group. Angiotensin-converting enzyme inhibitors/ARBs and physical activity were not different between groups. Sinus rhythm was present in 49 (46%) targeted vs. 43 (39%) conventional group patients at 5 years (odds ratio 1.297, lower limit of 95% confidence interval 0.756, P = 0.346). Cardiovascular mortality and morbidity occurred in 20 (19%) in the targeted and 15 (14%) conventional group patients, P = 0.353., Conclusion: In patients with early persistent AF and HF superiority of targeted therapy in sinus rhythm maintenance could not be preserved at 5-year follow-up. Cardiovascular outcome was not different between groups., Trial Registration Number: Clinicaltrials.gov NCT00877643., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control., Methods and Results: In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93)., Conclusion: In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)