Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry.

BACKGROUND: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. RESULTS: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA2DS2-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P=0.001). Acute major adverse events occurred in 1.9% of patients. CONCLUSIONS: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

Effect of early cryoballoon ablation on atrial fibrillation recurrence-A Danish nationwide register study.

INTRODUCTION: Cryoballoon ablation is a safe and efficient rhythm control strategy in atrial fibrillation (AF) patients. The impact of time from diagnosis to ablation is unclear. The aim of this study was to examine the impact of timing of first-time cryoballoon ablation on AF recurrence in a nationwide cohort of AF patients. METHODS AND RESULTS: From nationwide registers, all AF patients ≥18 years of age who underwent first-time AF cryoballoon ablation in Denmark from 2012 to 2018 were included. The AF patients were stratified by ablation timing: Early group (≤1 year after AF diagnosis), intermediate group (1-3 years after AF diagnosis), and late group (≥3 years after AF diagnosis). By adjusted Cox regression models, the effect of timing on AF recurrence was examined. This study included 1064 AF patients with a median age of 63 years. Most patients were male (66%) and had paroxysmal AF (67%). The 1-year risk of AF recurrence increased from 31% in the early group to 41% and 44% in the intermediate and late group. The hazard ratios (95% confidence intervals) were 1.28 (0.95, 1.74) in the intermediate group and 1.42 (1.09, 1.86) in the late group when compared to the early group. Continuous diagnosis-to-ablation time seemed to have the greatest impact on AF recurrence within the first 2 years. CONCLUSION: In AF patients undergoing cryoballoon ablation, late timing of ablation was associated with a significantly higher AF recurrence rate when compared to early timing of ablation. These findings support early cryoballoon ablation to improve the outcomes after ablation.

Dual energy for pulmonary vein isolation using dual-energy focal ablation technology integrated with a three-dimensional mapping system: SmartfIRE 3-month results.

AIMS: Contact force (CF)-sensing radiofrequency (RF) catheters with an ablation index have shown reproducible outcomes for the treatment of atrial fibrillation (AF) in large multicentre studies. A dual-energy (DE) focal CF catheter to deliver RF and unipolar/biphasic pulsed field ablation (PFA), integrated with a three-dimensional (3D) mapping system, can provide operators with additional flexibility. The SmartfIRE study assessed the safety and efficacy of this novel technology for the treatment of drug-refractory, symptomatic paroxysmal AF. Results at 3 months post-ablation are presented here. METHODS AND RESULTS: Pulmonary vein isolation (PVI) was performed using a DE focal, irrigated CF-sensing catheter with the recommendation of PFA at posterior/inferior and RF ablation at the anterior/ridge/carina segments. Irrespective of energy, a tag size of 3 mm; an inter-tag distance ≤6 mm; a target index of 550 for anterior, roof, ridge, and carina; and a target index of 400 for posterior and inferior were recommended. Cavotricuspid isthmus ablation was permitted in patients with documented typical atrial flutter. The primary effectiveness endpoint was acute procedural success. The primary safety endpoint was the rate of primary adverse events (PAEs) within 7 days of the procedure. A prespecified patient subset underwent oesophageal endoscopy (EE; 72 h post-procedure), neurological assessment (NA; pre-procedure and discharge), and cardiac computed tomography (CT)/magnetic resonance angiogram (MRA) imaging (pre-procedure and 3 months post-procedure) for additional safety evaluation, and a mandatory remapping procedure (Day 75 ± 15) for PVI durability assessment. Of 149 patients enrolled between February and June 2023, 140 had the study catheter inserted (safety analysis set) and 137 had ablation energy delivered (per-protocol analysis set). The median (Q1/Q3) total procedure and fluoroscopy times were 108.0 (91.0/126.0) and 4.2 (2.3/7.7) min (n = 137). The acute procedural success rate was 100%. First-pass isolation was achieved in 89.1% of patients and 96.8% of veins. Cavotricuspid isthmus ablations were successfully performed in 12 patients [pulsed field (PF) only: 6, RF only: 5, and RF/PF: 1]. The PAE rate was 4.4% [6/137 patients; 2 pulmonary vein (PV) stenoses, 2 cardiac tamponades/perforations, 1 stroke, and 1 pericarditis]. No coronary artery spasm was reported. No oesophageal lesion was seen in the EE subset (0/31, 0%). In the NA subset (n = 30), microemboli lesions were identified in 2 patients (2/30, 6.7%), both of which were resolved at follow-up; only 1 was symptomatic (silent cerebral lesion, 3.3%). In the CT/MRA subset (n = 30), severe PV narrowing (of >70%) was detected in 2 patients (2/30, 6.7%; vein level 2/128, 1.6%), of whom 1 underwent dilatation and stenting and 1 was asymptomatic; both were associated with high index values and a small inter-tag distance. In the PV durability subset (n = 30), 100/115 treated PVs (87%) were durably isolated and 18/30 patients (60.0%) had all PVs durably isolated. CONCLUSION: A DE focal CF catheter with 3D mapping integration showed a 100% acute success rate with an acceptable safety profile in the treatment of paroxysmal AF. Prespecified 3-month remapping showed notable PVI durability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05752487.

Long-term outcomes of the pentaspline pulsed-field ablation catheter for the treatment of paroxysmal atrial fibrillation: results of the prospective, multicentre FARA-Freedom Study.

AIMS: Pulmonary vein isolation (PVI) is a well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long-term efficacy and safety data demonstrating single-procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate the long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS AND RESULTS: FARA-Freedom, a prospective, non-randomized, multicentre study, enrolled patients with PAF undergoing de novo PVI with PFA, who were followed for 12 months with weekly transtelephonic monitoring and a 72-h Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success, which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. The study enrolled 179 PAF patients (62 ± 10 years, 39% female) at 13 centres. At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high, with 88.4 and 90.3% with weekly events and 72-h Holter monitors, respectively. Freedom from the composite primary effectiveness endpoint was 66.6%, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in two patients (1.1%), one tamponade and one transient ischaemic attack. There was no coronary spasm, PV stenosis, or AE fistula. There were four cases of transient phrenic nerve palsy, but all resolved during the index procedure. CONCLUSION: In this prospective, non-randomized, multicentre study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigourous endpoint definitions and high monitoring compliance and demonstrated favourable safety. REGISTRATION: Clinical Trials.gov Identifier: NCT05072964 (sponsor: Boston Scientific Corporation).

MRI-Detected Brain Lesions and Cognitive Function in Patients With Atrial Fibrillation Undergoing Left Atrial Catheter Ablation in the Randomized AXAFA-AFNET 5 Trial.

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.

Differential gap location after radiofrequency versus cryoballoon pulmonary vein isolation: Insights from a randomized trial with protocol-mandated repeat procedure.

INTRODUCTION: Reconnections to pulmonary vein (PV) triggers of atrial fibrillation (AF) are the primary cause of AF recurrence after PV isolation (PVI) with radiofrequency (RF) or cryoballoon catheter ablation (CRYO), but method-specific contributions to PV reconduction pattern and conductive gap location are incompletely understood. METHODS: The objective of this radiofrequency versus cryoballoon catheter ablation for paroxysmal atrial fibrillation substudy was to determine procedure-specific patterns of PV reconduction in a randomized population with protocol-mandated repeat procedures, irrespective of AF recurrence. Each PV was assessed in turn and PV reconnection sites were identified by high-density electroanatomical mapping and locating the earliest activation site. Gap locations were verified by PV re-isolation. RESULTS: In 98 patients, 81% versus 76% previously isolated PVs remained isolated after CRYO versus RF (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.18; p = .28). There were no significant differences for any PV: left superior PV: 90% versus 80%; left inferior PV: 80% versus 78%; right superior PV: 81% versus 80%, and right inferior PV: 76% versus 73%. For each reconnected PV, 34% of ipsilateral PVs were also reconnected after CRYO compared with 64% after RF (RR: 0.54; 95% CI: 0.32-0.90; p = .01). After RF, gaps were clustered by the carina and adjacent segments, whereas they were more heterogeneously distributed after CRYO. CONCLUSION: Although RF and CRYO produce similar proportions of durably isolated PVs, gap locations appear to develop in procedure-specific patterns. After RF, ipsilateral PV reconduction is more frequent and gap sites cluster by the carina, suggesting that this region should be selectively ablated for more durable PVI.

Early recurrence of atrial tachyarrhythmia indicates pulmonary vein reconduction independent of blanking period duration in the RACE-AF trial.

INTRODUCTION: Atrial tachyarrhythmia recurrence during the blanking period (early ATA) after pulmonary vein isolation (PVI) is associated with an increased risk of later recurrence, but its relationship with pulmonary vein reconduction (PVR) is poorly understood. The objective of the present study was to evaluate the relationship between early ATA and PVR. Second, to provide data on the optimal blanking period by (a) evaluating how the predictive values of ATA for PVR are affected by blanking period duration, and (b) assessing the temporal development in atrial fibrillation (AF) burden. METHODS: In this RACE-AF substudy, 91 patients with paroxysmal AF undergoing PVI randomized to radiofrequency or cryoballoon ablation were included. All patients received an implantable cardiac monitor and underwent a protocol-mandated repeat procedure after 4-6 months for assessment of PVR. ATA ≥ 30 s. ≤ 90 days after PVI constituted early ATA. RESULTS: PVR was found in 37/54 (69%) patients with early ATA and in 11/37 (30%) patients without (p < .001). The positive predictive value of ATA for PVR was independent of blanking period duration (range 0-90 days). In both patients with and without PVR, AF burden was higher in the first month after PVI, but AF burden from the second month was similar to AF burden after the conventional blanking period. CONCLUSION: Early ATA indicates PVR, and the positive predictive value is independent of the blanking period duration. Altogether, the results of this study support substantially shortening the blanking period after PVI for paroxysmal AF.

Short- and long-term risk of atrial fibrillation recurrence after first time ablation according to body mass index: a nationwide Danish cohort study.

AIMS: Overweight is associated with increased risk of atrial fibrillation (AF), but the impact of overweight and AF recurrence after ablation is less clear. Despite this, an increasing number of AF ablations are carried out in overweight patients. We investigated the impact of body mass index (BMI) on AF recurrence rates after ablation. METHODS AND RESULTS: Through Danish nationwide registers, all patients undergoing first-time AF ablation between 2010 and 2018 were identified. Exposure of interest was BMI. The primary outcome was recurrent AF, defined from either any usage of antiarrhythmic medication, AF hospitalization, cardioversion, or re-ablation. A total of 9188 patients were included. Median age and interquartile range was 64 (60-75) in the normal-weight group and 60 (53-66) in the morbidly obese. There was an increase in comorbidity burden with increasing BMI, including a higher prevalence of heart failure, chronic obstructive pulmonary disease, diabetes, and hypertension. At 1- and 5-year follow ups, recurrence rates of AF increased incrementally by BMI categories. The hazard ratios and 95% confidence intervals of recurrent AF after ablation were 1.15 (1.07-1.23), 1.18 (1.09-1.28), and 1.26 (1.13-1.41) in overweight, obese, and morbidly obese, respectively, compared with normal-weight patients. Procedure duration and X-ray dose exposure also increased with increasing BMI. CONCLUSION: Following AF ablation, recurrence rates of AF increased incrementally with increasing BMI. Therefore, aggressive weight management pre ablation in overweight patients could potentially provide substantial benefits and improve short- and long-term outcomes after ablation.

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

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

Posterior wall isolation in persistent atrial fibrillation feasibility, safety, durability, and efficacy.

INTRODUCTION: Posterior wall isolation (PWI) added to pulmonary vein isolation (PVI) is increasingly used despite limited evidence of clinical benefit. We investigated the feasibility, durability, and efficacy of index-procedure PVI + PWI radio frequency ablation (RFA) in patients with persistent atrial fibrillation (PeAF). METHODS AND RESULTS: Twenty-four patients with PeAF participated in the prospective PeAF-Box study and underwent RFA with wide area circumferential ablation, roof- and inferior lines to achieve PVI + PWI at index procedure. Follow-up included monitoring by an implantable cardiac monitor, esophagoscopy and mandated invasive lesion-reassessment at 6 months. PWI was achieved at minor procedural cost in all patients following PVI. In 33% of patients a median of three ablations in the narrow zone between the center of the posterior wall (PW) and the posterior right carina was pivotal for swift achievement of PWI. At the 6-month reassessment procedure 85% (95% confidence interval [CI]: 77%-92%) of pulmonary veins (PVs) and 46% (95% CI: 26%-67%) of PWs remained durably isolated. AF recurred in 25% and was associated with PV-reconnection (p = .02) but not PW-reconnection (p = .27). AF-burden was 0% (interquartile range [IQR]: 0%-0%) overall and after recurrence 1% (IQR: 0%-7%). CONCLUSION: Index procedure PVI + PWI for PeAF was feasible when recognizing that limited ablation in a PW center-to-right-carina zone was required in a subset of patients. Despite limited chronic PWI durability this strategy was followed by low AF-burden. A PVI + PWI strategy appears promising in ablation for PeAF.

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

AIMS: Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the 'real world' performance of the only approved PFA catheter, including acute effectiveness and safety-in particular, rare oesophageal effects and other unforeseen PFA-related complications. METHODS AND RESULTS: This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7-291), full cohort included 1758 patients: mean age 61.6 years (range 19-92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9-100%). Procedure time was 65 min (38-215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). CONCLUSION: In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of 'generic' catheter complications (tamponade, stroke) underscores the need for improvement.

Protocol for detecting unrecognized sleep apnea in patients with atrial fibrillation by a home-monitoring device: the DAN-APNO study.

BACKGROUND: Determining the presence of modifiable risk factors for atrial fibrillation (AF), such as sleep apnea is of clinical importance due to the potential impact targeting these risk factors can have on the progression and burden of AF. Using new digital-based technology is a promising solution to the underreporting of sleep apnea highlighted by academical societies in recent years. The aim of this study is to report the prevalence and severity of sleep apnea in patients with AF and, secondarily, assess the accuracy and feasibility of a new home-screening device for sleep apnea (NightOwl™ by Ectosense). METHODS: DAN-APNO is a cross-sectional study at the Department of Cardiology, Herlev-Gentofte Hospital recruiting patients with AF referred to anticoagulation initiation aged 18 to 90 years without known sleep apnea. At least 150 patients will be recruited and undergo medical history, clinical evaluation, several sleep-apnea questionnaires, and a sleep-recording evaluation for four nights with sleep apnea home-monitoring device NightOwl™. Additionally, the first 20 participants and participants with moderate-severe sleep apnea by screening are referred to cardio-respiratory monitoring (CRM). This clinical evaluation allows the comparison of standard evaluation method and the NightOwl™. Clinical measures include Apnea-Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), pulse rate, as well as questionaries about sleep apnea assessment and the clinical feasibility of the NightOwl™ device. Main outcomes comprise analysis of the prevalence and severity of sleep apnea, and clinical and demographic predictors of moderate and severe sleep apnea. In addition, correlation analyses for accuracy measures between CRM and NightOwl™ will be conducted along with patient ease-of-use and satisfaction questionnaires. DISCUSSION: This study is limited by selection bias; only patients with atrial fibrillation from anticoagulation clinic is asked to participate, which could limit the generalizability of our results. However, this study aims to test whether a miniaturized simple home-monitoring device for detecting sleep apnea in patients with AF potentially can evaluate sleep apnea more conveniently and easier. Trial Registration The study is registered the 18-02-2021 at clinicaltrials.gov with registration number: NCT04760002.

Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers.

INTRODUCTION: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). METHODS: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed. RESULTS: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731). CONCLUSION: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.

Catheter ablation for atrial fibrillation is associated with lower incidence of heart failure and death.

AIMS: Catheter ablation for atrial fibrillation (CAF) improves symptoms, but whether CAF improves outcome is less clear. The purpose of this study was to investigate whether CAF is associated with improved outcome in atrial fibrillation (AF) patients with previous direct current (DC) cardioversion. METHODS AND RESULTS: We performed a nationwide cohort study including all patients who underwent their 1st direct current cardioversion for AF in the period 2003-15 (N = 25 439). End points were all-cause death, cardiovascular death, stroke/thromboembolism, and incident heart failure (HF). Catheter ablation for AF was treated as a time-varying covariate and the association with outcome was assessed using Cox regression. We also constructed a propensity-matched cohort and assessed the association between CAF and outcome. Median follow-up was 5.3 years (inter-quartile range 3.0-8.7 years). A total of 3509 patients (13.8%) underwent CAF during the study period. Following adjustment for age, gender, comorbidities, medications, educational level, household income, and CHA2DS2VASc score, CAF was associated with reduced risks of all-cause death, cardiovascular death, and incident HF [all-cause death: hazard ratio (HR) 0.69, P < 0.001; cardiovascular death: HR 0.68, P = 0.003; incident HF: HR 0.76, P = 0.011]. Catheter ablation for AF was not associated with a reduced risk of stroke/thromboembolism. These results were replicated in a propensity-matched cohort. CONCLUSION: In AF patients with a prior DC cardioversion, CAF was associated with a reduced risk of all-cause and cardiovascular death. This may be due to a reduced risk of HF.

QT as a predictor of recurrence after atrial fibrillation ablation and the impact of amiodarone: results from the placebo-controlled AMIO-CAT trial.

AIMS: Prolonged corrected QT interval (QTc) might be associated with arrhythmia recurrence after atrial fibrillation (AF) ablation. The effect of short-term amiodarone in this setting remains unknown. This study seeks to quantify short-term amiodarone's impact on QTc, and to investigate QTc and amiodarone treatment as predictors of recurrence of arrhythmia after ablation. METHODS AND RESULTS: The Short-term AMIOdarone treatment after CATheter ablation for atrial fibrillation (AMIO-CAT) trial randomized patients to 8 weeks of oral amiodarone or placebo following AF ablation. Scheduled and symptom-driven 12-lead electrocardiography and 3-day Holter-monitorings were performed. The endpoint was atrial fibrillation, atrial flutter or atrial tachycardia (AF/AT) lasting >30 s. The cut-off for prolonged QTc was 450 ms for men and 460 ms for women. A total of 212 patients were included, of which 108 were randomized to amiodarone and 104 to placebo. From baseline to 1 month QTc in the amiodarone group increased by 27 (±30) ms, while at 6 months QTc had normalized. After 3-months of blanking, new AF/AT recurrence was detected in 63% of patients with prolonged QTc vs. 41% of patients with normal QTc at baseline, and in multivariate Cox regression, prolonged QTc was associated with AF/AT recurrence [hazard ratio (HR) 2.19, P = 0.023]. Among patients with baseline QTc below median, amiodarone treatment decreased the rate of AF/AT recurrences (HR 0.43, P = 0.008). CONCLUSIONS: Amiodarone increased QTc with 27 ms compared to placebo, and this effect decreased rapidly after drug discontinuation. Prolonged QTc at baseline independently predicted AF/AT recurrence, and baseline QTc identified patients who would possibly benefit from short-term amiodarone following ablation.

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

Temporal trends in atrial fibrillation recurrence rates after ablation between 2005 and 2014: a nationwide Danish cohort study.

Aims: During the last decade, ablation has increasingly been used in rhythm control management of patients with atrial fibrillation (AF). Over time, experience and techniques have improved and indications for ablation have expanded. The purpose of this study was to investigate whether the recurrence rate of AF following ablation has improved during last decade. Methods and results: Through Danish nationwide registers, all patients with first-time AF ablation, between 2005 and 2014 in Denmark were identified. Recurrent AF after ablation was identified with 1 year follow-up. A total of 5425 patients undergoing first-time ablation were included. While patient median age increased over time the median AF duration prior to ablation decreased. The rates of recurrent AF decreased from 45% in 2005-2006 to 31% 2013-2014 with the relative risk of recurrent AF almost halved with an odds ratio of 0.57 [95% confidence intervals (95% CI) 0.47-0.68] in 2013-2014 compared with patients undergoing ablation in 2005-2006. Female gender, hypertension, AF duration >2 years, and cardioversion within 1 year prior to ablation were all associated with an increased risk of recurrent AF. Conclusion: One year risk of recurrent AF following first-time ablation has almost halved from 2006 to 2014. Hypertension, female sex, cardioversion 1 year prior to ablation, and AF duration for more than 2 years all increased the associated risk of recurrent AF.

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation.

Aims: It is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested. Methods and results: We compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA, international normalized ratio 2-3) in atrial fibrillation patients at risk of stroke a prospective, open, multi-centre study with blinded outcome assessment. Primary outcome was a composite of death, stroke, or bleeding (Bleeding Academic Research Consortium 2-5). A high-resolution brain magnetic resonance imaging (MRI) sub-study quantified acute brain lesions. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at baseline and at end of follow-up. Overall, 674 patients (median age 64 years, 33% female, 42% non-paroxysmal atrial fibrillation, 49 sites) were randomized; 633 received study drug and underwent ablation; 335 undertook MRI (25 sites, 323 analysable scans). The primary outcome was observed in 22/318 patients randomized to apixaban, and in 23/315 randomized to VKA {difference -0.38% [90% confidence interval (CI) -4.0%, 3.3%], non-inferiority P = 0.0002 at the pre-specified absolute margin of 0.075}, including 2 (0.3%) deaths, 2 (0.3%) strokes, and 24 (3.8%) ISTH major bleeds. Acute small brain lesions were found in a similar number of patients in each arm [apixaban 44/162 (27.2%); VKA 40/161 (24.8%); P = 0.64]. Cognitive function increased at the end of follow-up (median 1 MoCA unit; P = 0.005) without differences between study groups. Conclusions: Continuous apixaban is safe and effective in patients undergoing atrial fibrillation ablation at risk of stroke with respect to bleeding, stroke, and cognitive function. Further research is needed to reduce ablation-related acute brain lesions.

Oral anticoagulation therapy after radiofrequency ablation of atrial fibrillation and the risk of thromboembolism and serious bleeding: long-term follow-up in nationwide cohort of Denmark.

AIM: To investigate the long-term risk of thromboembolism and serious bleeding associated with oral anticoagulation (OAC) therapy beyond 3 months after radiofrequency ablation (RFA) of atrial fibrillation (AF). METHODS AND RESULTS: Linking Danish administrative registries, 4050 patients undergoing first-time RFA (2000-11) were identified. Risk of thromboembolism and serious bleeding according to OAC therapy were analysed by incidence rates (presented per 100 person-years) and Cox proportional-hazard models. The median age was 59.5 years (interquartile range, IQR: 52.8-65.2); 26.5% were females. During a median follow-up of 3.4 years (IQR: 2.0-5.6), 71 (1.8%) thromboembolism cases were identified, where incidence rates with and without OAC were 0.56 (0.40-0.78)95%CI and 0.64 (0.46-0.89)95%CI, respectively. Oral anticoagulation discontinuation remained insignificant [hazard ratio 1.42(0.86-2.35)95%CI] in multivariable analysis. Beyond 3 months after RFA 87 (2.1%) serious bleedings occurred; incidence rates with and without OAC were 0.99 (0.77-1.27)95%CI and 0.44 (0.29-0.65)95%CI, respectively. Oral anticoagulation therapy was significantly associated with serious bleeding risk [hazard ratio 2.05(1.25-3.35)95%CI]. In an age- and gender-matched cohort (1 : 4) of 15 848 non-ablated AF patients receiving rhythm-control therapy, thromboembolic rates with and without OAC were 1.34 (1.21-1.49)95%CI and 2.14 (1.98-2.30)95%CI, respectively. Adjusted incidence rate ratio was 0.53 (0.43-0.65)95%CI favouring RFA cohort. CONCLUSION: Thromboembolic risk beyond 3 months after RFA was relatively low compared with a matched non-ablated AF cohort. With cautious interpretation due to low number of events, serious bleeding risk associated with OAC seems to outweigh the benefits of thromboembolic risk reduction. Randomized studies are warranted to test our results.