BACKGROUND:Atrial fibrillation (AF) increases cardiovascular risk in patients with chronic kidney disease (CKD). The safety and efficacy of early rhythm control (ERC) in patients with CKD is not fully established. OBJECTIVES:This predefined secondary analysis of the EAST-AFNET 4 trial assessed the effectiveness and safety of ERC in patients with CKD defined by estimated glomerular filtration rate (GFR). METHODS:EAST-AFNET 4 randomized patients with recently diagnosed AF and comorbidities to ERC or usual care (UC). Key outcomes were analyzed by Kidney Disease Improving Global Outcomes defined CKD groups. The primary efficacy outcome combined cardiovascular death, stroke, hospitalization for worsening heart failure, or acute coronary syndrome. The safety outcome combined death, stroke, and serious rhythm control-related adverse events. Recurrent AF was a secondary outcome. RESULTS:Baseline creatinine was available in 2,742 of 2,789 (98.3%) patients. In this study, 23% had CKD (GFR: <60 mL/min/1.73 m2). Patients with CKD were older (CKD: 74 ± 7.4 years; no CKD: 69 ± 8.3 years; P < 0.001), had higher CHA2DS2-VASc scores (CKD: 4 ± 1.4; no CKD: 3.2 ± 1.2; P < 0.001), and more primary outcome events over 5.1 years of follow-up (HR: 0.98 per mL GFR decrease [95% CI: 0.97-0.99 per mL GFR decrease]). ERC reduced the primary outcome with and without CKD (no CKD: ERC: 3.4%/100 patient-years; UC: 4.1%/100 patient-years; HR: 0.84; P < 0.001; CKD: ERC: 5.8%/100 patient-years; UC: 8.5%/100 patient-years; HR: 0.67; P < 0.001; Pinteraction = 0.133). CKD increased safety outcomes without interaction with ERC (Pinteraction = 0.927). Patients with CKD experienced more AF recurrences with UC (Pinteraction = 0.036). CONCLUSION:ERC effectively and safely reduces cardiovascular events in patients with recently diagnosed AF and stroke risk factors with and without CKD. (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST); NCT01288352).

Left bundle branch area pacing (LBBAP) is a novel physiological pacing modality and is regarded as a viable alternative to His bundle pacing. LBBAP has mostly been performed with the lumen-less permanent pacing lead (SelectSecure™ Model 3830, Medtronic, Inc.) with a fixed helix. The aim of this study was to compare the non-stylet driven lumen-less lead (LLL) (Medtronic 3830) with a standard stylet-driven active fixation lead (SDL) (Tendril™ STS Model 2088TC-38, Abbott Laboratories) in terms of lead parameters, procedural success and complication rates. Patients receiving a LBBA pacemaker in the Isala Hospital, The Netherlands, were prospectively enrolled. The majority received a standard right ventricular (RV) lead as backup, the implanter chose between LLL and SDL for the LBBAP lead. The study included 94 patients with a mean follow-up of 30 weeks. 30/31 LLL procedures were successful, compared with 62/63 in the SDL group. Including the participants that lost LBBAP during follow-up resulted in success rates of 90.3

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

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.

Abstract Background In the treatment of patients with symptomatic atrial fibrillation (AF) reducing AF-related symptoms and improving health-related quality of life (HRQol) are important drivers in the decision for pulmonary vein isolation (PVI). Eventhought the majority of PVI patients has improved HRQoL after PVI, up to a third of patients do not. We aim to assess the association between various patient characteristics, intervention and outcome variables and HRQol both prior to and one-year after PVI with specific attention for those groups that did not improve or were still impaired in HRQoL after PVI. Methods In this observational, retrospective multicenter cohort study, we used data from 8 hospitals participating within the Netherlands Heart Registration (NHR), a non-profit organisation facilitating high-quality registration of patients undergoing cardiac interventions within the Netherlands. Patients who underwent PVI between January 2016 and December 2019 and completed the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire both prior to and one-year after were included (N=2534). To interpret the relevance of findings, accepted cut-off values for the AFEQT Overall summary score were used; <80 points for impaired HRQoL and a delta of ≥5 points for clinically meaningful improvement. Results The majority of the population were men (65.7%) with normal left ventricular ejection fraction (87.1%), paroxysmal AF (77.1%) and a low median CHA₂DS₂-VASc score of 1 (interquartile range, 1–2). The mean AFEQT score was 55.6 ± 19.7 prior to intervention and 79.8 ± 20.2 one-year after PVI. Despite this major increase in mean AFEQT score, we found 39.5% of the population still impaired in HRQol (<80 points) one-year after PVI and 19.2% of the population failed to achieve a clinically meaningful improvement (delta of ≥5 points). Lower baseline AFEQT score (odds ratio [OR], 0.96 [per 1-point increase]; 95% CI, 0.96-0.97; P<0.001) and female sex (odds ratio [OR], 1.42; 95% CI, 1.16-1.75; P<0.001) found to be the most prominent related factors with impaired HRQol one-year after PVI. For failure to achieve clinically meaningful improvement higher baseline AFEQT score (odds ratio [OR], 1.04 [per 1-point increase]; 95% CI, 1.04-1.05; P<0.001) was strongly associated. Other independent risk factors were age (impaired HRQol); BMI (impaired HRQOL); CHA₂DS₂-VASc score (failure to achieve clinically meaningful improvement) and prior catheter ablation for AF (impaired HRQOL and failure to achieve clinically meaningful improvement). Conclusion Despite a major increase in HRQol across the population after PVI, over one third of patients were still impaired in HRQoL after PVI. Several factors were identified which could guide patient counseling for the best fitting treatment for atrial fibrillation.

Background Untreated atrial fibrillation (AF) often results in increased morbidity and mortality. Opportunistic AF screening in persons aged ≥ 65 years is recommended to identify patients with AF in order to prevent AF-related complications. Objective The aim of this study was to assess the feasibility of screening persons for AF with the Kardia mobile electrocardiogram device (MED) and to determine the percentage of newly detected AF cases by selective population screening in the Netherlands. Methods Persons aged ≥ 65 years, without a medical history of AF, in nursing homes, at public events or visiting the general practitioner (GP) were approached to participate. A Kardia MED smartphone ECG (sECG) was recorded and the CHA 2 DS 2 -VASc score was calculated. An automated AF algorithm classified the sECGs as ‘sinus rhythm’, ‘AF’ or ‘unclassified’. In the case of AF, participants were referred to their GP. All sECGs were assessed by blinded experts. Results A total of 2168 participants were screened for AF. According to the expert’s interpretation, 2.5% had newly detected AF, of whom 76.4% never experienced palpitations and 89.1% had a CHA 2 DS 2 -VASc score ≥ 2. The algorithm result was unclassified in 12.2% of cases, of which 95.5% were interpretable by experts. With expert opinion as the gold standard and excluding unclassified sECGs, the Kardia MED’s negative and positive predictive value for detecting AF was 99.8% and 60.0%, respectively. Conclusion Screening for AF using the Kardia MED is feasible and results in 2.5% newly detected AF cases. Expert interpretation of algorithm outcomes AF and unclassified is recommended.

Hypertension is an important risk factor for cardiovascular disease. In the Netherlands, there are approximately 2.8 million people with hypertension. Despite treatment recommendations including lifestyle changes and antihypertensive drugs, most patients do not meet guideline-recommended blood pressure (BP) targets. In order to improve BP control and lower the risk of subsequent cardiovascular events, renal sympathetic denervation (RDN) has been introduced and studied as a non-pharmacological approach. While early data on the efficacy of RDN showed conflicting results, improvements in treatment protocols and study design resulted in robust new evidence supporting the potential of the technology to improve patient care in hypertensive subjects. Recently, 5 randomised sham-controlled trials demonstrated the safety and efficacy of the technology. Modelling studies have further shown that RDN is cost-effective in the Dutch healthcare setting. Given the undisputable disease burden along with the shortcomings of current therapeutic options, we postulate a new, clearly framed indication for RDN as an adjunct in the treatment of hypertension. The present consensus statement summarises current guideline-recommended BP targets, proposed workup and treatment for hypertension, and position of RDN for those patients with primary hypertension who do not meet guideline-recommended BP targets (see central illustration).

The highlights from the March subspecialty journals cover several fascinating topics.An open-label dose escalation study of oral inhaled flecainide solution for cardioversion of atrial fibrillation is described in Circulation Arrhythmia and Electrophysiology.A randomized trial comparing an herbal therapy with losartan for hypertension is presented in Circulation: Cardiovascular Quality and Outcomes.A novel small molecule that activates the sarcomere and increases contractility is described in a series of tissue models in Circulation: Heart Failure.The association of breast arterial calcification on mammography with cardiovascular disease in postmenopausal women is evaluated in Circulation: Cardiovascular Imaging.Finally, the costs associated with surgical versus transcatheter aortic valve replacement are compared in Circulation: Cardiovascular Interventions.

ObjectiveAtrial 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.MethodsIn 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.ResultsMean 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.ConclusionIn 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 numberNCT02726698.

Abstract Aims Treatment patterns were compared between randomized groups in EAST-AFNET 4 to assess whether differences in anticoagulation, therapy of concomitant diseases, or intensity of care can explain the clinical benefit achieved with early rhythm control in EAST-AFNET 4. Methods and results Cardiovascular treatment patterns and number of visits were compared between randomized groups in EAST-AFNET 4. Oral anticoagulation was used in >90% of patients during follow-up without differences between randomized groups. There were no differences in treatment of concomitant conditions between groups. The type of rhythm control varied by country and centre. Over time, antiarrhythmic drugs were given to 1171/1395 (84%) patients in early therapy, and to 202/1394 (14%) in usual care. Atrial fibrillation (AF) ablation was performed in 340/1395 (24%) patients randomized to early therapy, and in 168/1394 (12%) patients randomized to usual care. 97% of rhythm control therapies were within class I and class III recommendations of AF guidelines. Patients randomized to early therapy transmitted 297 166 telemetric electrocardiograms (ECGs) to a core lab. In total, 97 978 abnormal ECGs were sent to study sites. The resulting difference between study visits was low (0.06 visits/patient/year), with slightly more visits in early therapy (usual care 0.39 visits/patient/year; early rhythm control 0.45 visits/patient/year, P < 0.001), mainly due to visits for symptomatic AF recurrences or recurrent AF on telemetric ECGs. Conclusion The clinical benefit of early, systematic rhythm control therapy was achieved using variable treatment patterns of antiarrhythmic drugs and AF ablation, applied within guideline recommendations.

Abstract Background Height, weight, and body mass index (BMI) are well established risk factors for atrial fibrillation (AF) but whether they are also predictors of successful pharmacological cardioversion of AF is unknown. Data from the open-label INSTANT study of flecainide acetate oral inhalation solution (FlecIH) for acute cardioversion of recent-onset symptomatic AF were examined to determine if these anthropometric measures are predictors of successful cardioversion of AF to sinus rhythm (SR) with FlecIH. Methods Logistic regression was performed on a broad array of patient and disease characteristics to identify predictors of cardioversion success at 90 minutes post-dose, and potential interactions were examined by boundary restriction analysis. Data are presented for patients receiving 120 mg FlecIH. Results Data from 81 patients (32.1% female) with a mean age of 59.8 years (range: 26.0, 84.0) were included in the analysis. This cohort had a mean weight of 87 kg (range: 57, 150), a mean height of 180 cm (range: 156, 199), and a mean BMI of 26.8 kg/m2 (range: 17.2, 37.9). A logistic regression model identified height, weight, and BMI as significant predictors of cardioversion success (p<0.01) and a boundary restriction analysis revealed a negative correlation between BMI and conversion rate across the entire dataset (see Figure 1). Clinically significant conversion rates were observed for patients with BMI values that were considered normal (BMI <25 kg/m2 = 53%; 95% CI: 36, 70), overweight (BMI ≥25 and <30 kg/m2 = 47%; 95% CI: 29, 64), and obese (BMI ≥30 and <35 kg/m2 = 43%; 95% CI: 17, 69); however, none of the severely obese patients (BMI ≥35 mg/m2) had their AF successfully converted to sinus rhythm (see Figure 2). Conclusions Successful cardioversion of recent onset AF with 120 mg FlecIH was observed in normal, overweight, and obese patients with BMI values <35 kg/m2; however, conversion rate decreases with increasing BMI. Further evaluation of FlecIH dosing in severely obese patients is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): InCarda Therapeutics

Abstract Introduction Pharmacological restoration of sinus rhythm (SR) in patients with symptomatic atrial fibrillation (AF) is expected to be accompanied by prompt alleviation of symptoms to avoid the need for electrical cardioversion (ECV) and/or hospitalization. The feasibility and safety of acute cardioversion of recent-onset (≤48 hours) symptomatic AF to SR with flecainide acetate oral inhalation (FlecIH) solution was shown in the Phase 2, open-label INSTANT trial. We examined symptoms, heart rate, time to discharge and need for ECV reported among patients in the INSTANT trial whose AF was successfully converted to SR (“conversion group”; N=25) versus those whose AF did not convert to SR (“no conversion group”; N=29). Methods Conversion success was determined using 12-lead Holter monitoring during a 90-minute observation period. Patients in the no conversion group were offered alternative treatment per the investigator discretion. Symptoms, vital signs, time to discharge, and the need for ECV were evaluated through Day 5. Results Data from 54 patients (33.3% female) with a mean age of 62.1 years and a mean BMI of 26.8 kg/m2 were analyzed. All patients reported at least one AF-related symptoms at baseline (palpitations=85%; dizziness=35%; shortness of breath=37%; chest discomfort=39%) and 83.3% presented with AF symptoms ≤24 hours in duration. At 90 minutes, 80.0% of the conversion group were asymptomatic compared to 37.9% of the no conversion group (p<0.001). Mean (SD) ventricular rate at 90 minutes was 70.6 (12.5) bpm in the conversion group compared to 100.4 (29.4) bpm in the no conversion group (p<0.001). Median time to discharge was 2.3 (IQR: 0.75) hours for the conversion group compared to 3.6 (IQR: 1.02) hours for the no conversion group (p=0.001). By Day 5, 23 (79.3%) patients in the no conversion group had undergone ECV; no patients in the conversion group experienced AF recurrence by Day 5 (0% required ECV; p<0.001). Conclusions Conversion of recent onset AF to SR with inhaled flecainide was associated with a reduction in symptoms, normalization of heart rate, rapid hospital discharge and avoidance of ECV during a 5-day follow-up period. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): InCarda Therapeutics

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation, Medtronic Background The incidence of atrial fibrillation (AF) increases exponentially with age. To which extend vascular aging is part of this process is unknown. Pulse wave velocity and carotid intima-media thickness are established markers for vascular aging and have been combined in a vascular aging index as published before(1). Purpose We aim to investigate if vascular age exceeds chronological age in our cohort with paroxysmal AF and if yes to which extend. Methods In this substudy from RACE V we included 295 patients with paroxysmal AF in which carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (IMT) were measured. To calculate vascular aging we used a logarithmic formula derived from the Malmö-Cancer-and-Diet study which yields a vascular age index derived from cfPWV, cIMT and chronological age. This vascular aging index (VAI) is a strong predictor of cardiovascular events. (1). All patients underwent cardiac echocardiography and had a native cardiac CT scan in which fat around the heart and coronary calcium were quantified. In 121 patients Agatston scores from the ascending aortic artery were also measured. Results Patients in this study had a mean chronological age of 63.8 ± 10.1 years and a vascular age of 71.4 ± 11.7 years. Vascular age was on average 9.3 ± 10.2 years higher than chronological age. Vascular age correlated significantly with markers for diastolic dysfunction, vascular calcification in the coronary arteries as well as the aorta and the amount of epicardial and pericardial fat (table 1). Conclusions In patients with PAF vascular age was on average 9.3 years higher than chronological age in our cohort. Advanced vascular age is represented by vascular and myocardial remodeling related to fibrosis, calcification and fat accumulation. The results suggest that in patients with AF enhanced inflammation is leading to fibrosis and calcification. Whether AF is a marker, a mechanism or both in advanced vascular aging warrants further study.

BACKGROUND:Persistent phrenic nerve palsy (PNP) is an established complication of atrial fibrillation (AF) ablation, especially during cryoballoon and thoracoscopic ablation. Data on persistent PNP reversibility is limited because most patients recover <24 h. This study aims to investigate persistent PNP recovery, freedom of PNP-related symptoms after AF ablation and identify baseline variables associated with the occurrence and early PNP recovery in a large nationwide registry study.METHODS:In this study, we used data from the Netherlands Heart Registration, comprising data from 9549 catheter and thoracoscopic AF ablations performed in 2016 and 2017. PNP data was available of 7433 procedures, and additional follow-up data were collected for patients who developed persistent PNP.RESULTS:Overall, the mean age was 62 ± 10 years, and 67.7% were male. Fifty-four (0.7%) patients developed persistent PNP and follow-up was available in 44 (81.5%) patients. PNP incidence was 0.07%, 0.29%, 1.41%, and 1.25%, respectively for patients treated with conventional-RF, phased-RF, cryoballoon, and thoracoscopic ablation respectively. Seventy-one percent of the patients fully recovered, and 86% were free of PNP-related symptoms after a median follow-up of 203 (113-351) and 184 (82-359) days, respectively. Female sex, cryoballoon, and thoracoscopic ablation were associated with a higher risk to develop PNP. Patients with PNP recovering ≤180 days had a larger left atrium volume index than those with late or no recovery.CONCLUSION:After AF ablation, persistent PNP recovers in the majority of patients, and most are free of symptoms. Female patients and patients treated with cryoballoon or thoracoscopic ablation are more prone to develop PNP.

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.

Background: We aimed to assess the prevalence of ischemic brain lesions detected by magnetic resonance imaging and their association with cognitive function 3 months after first-time ablation using continuous oral anticoagulation in patients with paroxysmal atrial fibrillation (AF). Methods: We performed a prespecified analysis of the AXAFA-AFNET 5 trial (Anticoagulation Using the Direct Factor Xa Inhibitor Apixaban During Atrial Fibrillation Catheter Ablation: Comparison to Vitamin K Antagonist Therapy), which randomized 674 patients with AF 1:1 to uninterrupted apixaban or vitamin K antagonist therapy before first-time ablation. Brain magnetic resonance imaging using fluid-attenuated inversion recovery and high-resolution diffusion-weighted imaging was obtained within 3 to 48 hours after AF ablation in all eligible patients enrolled in 25 study centers in Europe and the United States. Patients underwent cognitive assessment 3 to 6 weeks before ablation and 3 months after ablation using the Montreal Cognitive Assessment (MoCA). Results: In 84 (26.1%) of 321 patients with analyzable magnetic resonance imaging, high-resolution diffusion-weighted imaging detected at least 1 acute brain lesion, including 44 (27.2%) patients treated with apixaban and 40 (24.8%) patients treated with vitamin K antagonist (P=0.675). Median MoCA score was similar in patients with or without acute brain lesions at 3 months after ablation (28 [interquartile range (IQR), 26–29] versus 28 [IQR, 26–29]; P=0.948). Cerebral chronic white matter damage (defined as Wahlund score ≥4 points) detected by fluid-attenuated inversion recovery was present in 130 (40.5%) patients and associated with lower median MoCA scores before ablation (27 [IQR, 24–28] versus 27 [IQR, 25–29]; P=0.026) and 3 months after ablation (27 [IQR, 25–29] versus 28 [IQR, 26–29]; P=0.011). This association was no longer significant when adjusted for age and sex. Age was associated with lower MoCA scores before ablation (relative risk, 1.02 per 10 years [95% CI, 1.01–1.03]) and 3 months after ablation (relative risk, 1.02 per 10 years [95% CI, 1.01–1.03]). Conclusions: Chronic white matter damage as well as acute ischemic lesions detected by brain magnetic resonance imaging were found frequently after first-time ablation for paroxysmal AF using uninterrupted oral anticoagulation. Acute ischemic brain lesions detected by high-resolution diffusion-weighted imaging were not associated with cognitive function at 3 months after ablation. Lower MoCA scores before and after ablation were associated only with older age, highlighting the safety of AF ablation on uninterrupted oral anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02227550.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pulmonary vein isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation. The POLARx cryoballoon, which maintains a constant balloon pressure during ablation, was recently introduced for the treatment of AF. We present a comparison of acute and follow-up efficacy and safety outcomes between POLARx and Arctic Front, a frequently used second-generation used cryoballoon. Methods 251 consecutive patients who underwent first-time cryoballoon AF ablation with POLARx (n=118) or Arctic Front (n=133) with a follow-up of at least 6 months, were retrospectively included. Results Of the total 251 patients who were included, mean age was 63 ± 9 years and 161 (64%) participants were male. The majority of the patients suffered from paroxysmal atrial fibrillation (95%). Follow-up success rates did not significantly differ between the POLARx (79%) and Artic Front (75%) groups at 6 months. Antiarrhythmic drug-use after the blanking period of 3 months was 9% for the POLARx group. Complication rates, excluding groin complications, were low in both study groups and were not significantly different (4% in POLARx vs 3% in Arctic Front). Procedure times (71 ± 23 minutes vs. 120 ± 36 minutes) and fluoroscopy times (20 ± 10 minutes vs. 33 ± 18 minutes) were both more favourable in the POLARx group. Lastly, nadir balloon temperatures were significantly lower (-57 ± 7 ºC vs -51 ± 7 ºC) for the POLARx group for all pulmonary veins (p<0.001). Conclusion Cryoballoon AF ablation with the POLARx cryoballoon results in similar success and complication rates at 6 months, in comparison with Arctic Front. Procedure and fluoroscopy times are shorter and balloon nadir temperatures are significantly lower for the POLARx cryoballoon. This can lead to optimal logistics and thus cost-effective use of lab and personnel.