A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Anticoagulation in device-detected atrial fibrillation with or without vascular disease: a combined analysis of the NOAH-AFNET 6 and ARTESiA trials.

BACKGROUND AND AIMS: The optimal antithrombotic therapy in patients with device-detected atrial fibrillation (DDAF) is unknown. Concomitant vascular disease can modify the benefits and risks of anticoagulation. METHODS: These pre-specified analyses of the NOAH-AFNET 6 (n=2534 patients) and ARTESiA (n=4012 patients) trials compared anticoagulation to no anticoagulation in patients with DDAF with or without vascular disease, defined as prior stroke/transient ischemic attack, coronary or peripheral artery disease. Efficacy outcomes were the primary outcomes of both trials, a composite of stroke, systemic arterial embolism (SE), myocardial infarction, pulmonary embolism or cardiovascular death, and stroke or SE. Safety outcomes were major bleeding or major bleeding and death. RESULTS: In patients with vascular disease (NOAH-AFNET 6 56%, ARTESiA 46.0%), stroke, myocardial infarction, systemic or pulmonary embolism, or cardiovascular death occurred at 3.9%/patient-year with and 5.0%/patient-year without anticoagulation (NOAH-AFNET 6), and 3.2%/patient-year with and 4.4%/patient-year without anticoagulation (ARTESiA). Without vascular disease, outcomes were equal with and without anticoagulation (NOAH-AFNET 6 2.7%/patient-year, ARTESiA 2.3%/patient-year in both randomised groups). Meta-analysis found consistent results across both trials (I2heterogeneity=6%) with a trend for interaction with randomised therapy (pinteraction=0.08). Stroke/SE behaved similarly. Anticoagulation increased major bleeding in vascular disease patients (edoxaban 2.1%/patient-year, no anticoagulation 1.3%/patient-year; apixaban 1.7%/patient-year; no anticoagulation 1.1%/patient-year; incidence rate ratio 1.55 [1.10-2.20]) and without vascular disease (edoxaban 2.2%/patient-year; no anticoagulation 0.6%/patient-year; apixaban 1.4%/patient-year; no anticoagulation 1.1%/patient-year, incidence rate ratio 1.93 [0.72-5.20]). CONCLUSIONS: Patients with DDAF and vascular disease are at higher risk of stroke and cardiovascular events and may derive a greater benefit from anticoagulation than patients with DDAF without vascular disease.

Expert opinion on design and endpoints for studies on catheter ablation of atrial fibrillation.

INTRODUCTION: Catheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. BACKGROUND: Studies on catheter ablation of AF may benefit from well-described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost-effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects. METHODS: A panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials. RESULTS: A comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm-related and other endpoints. CONCLUSION: This expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology. CONDENSED ABSTRACT: Recent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.

Representation of obesity in contemporary atrial fibrillation ablation randomized controlled trials.

BACKGROUND: The prevalence and impact of obesity on outcomes of atrial fibrillation (AF) ablation randomized controlled trials (RCTs) have not been well studied. OBJECTIVE: To examine the proportion of participants with obesity enrolled in RCTs of AF ablation and outcomes of ablation when subgroup analysis of participants with obesity were available. METHODS: We systematically searched PubMed and EMBASE for AF ablation RCTs published between January 1, 2015 to May 31, 2022. When body mass index (BMI) data were available, normal distribution was assumed and a z score was used to estimate the proportion of obesity. Results categorized by BMI or body weight status were reviewed. Authors were contacted for additional information. RESULTS: Of 148 eligible RCTs with 30174 participants, 144 (97.30%) RCTs did not report the proportion of participants with obesity, while published information regarding BMI was available in 63.51%. Three trials excluded patients based on BMI. Using reported BMI, we estimated the proportion of participants with obesity varied greatly across these trials, ranging from 5.82%-71.9% (median 38.02%, interquartile 29.64%, 49.10%). Patients with obesity were represented in a greater proportion among trials conducted in North America (50.23%) and Asia (44.72%), compared to others (32.16%), p < .001. Subgroup analysis or analysis adjusting for BMI was reported in only 13 (8.78%) RCTs; four (30.77%) of these suggested that BMI or body weight might negatively affect primary outcomes. CONCLUSION: Obesity is a common comorbidity among AF patients. However, most AF ablation RCTs underreported the proportion of participants with obesity and its impact on the primary outcomes.

Effect of dronedarone vs. placebo on atrial fibrillation progression: a post hoc analysis from ATHENA trial.

AIMS: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. METHODS AND RESULTS: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as ≥6 months of AF/AFL until end of study) or permanent SR (defined as ≥6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). CONCLUSION: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling. CLINICAL TRIAL REGISTRATION: NCT00174785.

Contemporary management of atrial fibrillation and the predicted vs. absolute risk of ischaemic stroke despite treatment: a report from ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Risk stratification in patients with atrial fibrillation (AF) is important to facilitate guideline-directed therapies. The Calculator of Absolute Stroke Risk (CARS) scheme enables an individualized estimation of 1-year absolute risk of stroke in AF. We aimed to investigate the predicted and absolute risks of ischaemic stroke, and evaluate whether CARS (and CHA2DS2-VASc score) may be useful for identifying high risk patients with AF despite contemporary treatment. METHODS: We utilized the EORP-AF General Long-Term Registry which prospectively enrolled patients with AF from 250 centres across 27 participating European countries. Patients with sufficient data to determine CARS and CHA2DS2-VASc score, and reported outcomes of ischaemic stroke were included in this analysis. The primary outcome of ischaemic stroke was recorded over a 2-year follow-up period. RESULTS: A total of 9444 patients were included (mean age 69.1 [±11.4] years; 3776 [40.0%] females). There was a high uptake (87.9%) of anticoagulation therapy, predominantly with vitamin K antagonist (50.0%). Over a mean follow-up period of 24 months, there were a total of 101 (1.1%) ischaemic stroke events. In the entire cohort, the median CARS and absolute annual risks of ischaemic stroke were 2.60 (IQR 1.60-4.00) and 0.53% (95%CI 0.43-0.64%), respectively. There was no statistical difference between the predictive performance of CARS and CHA2DS2-VASc score (0.621 [95%CI 0.563-0.678] vs. 0.626 [95%CI 0.573-0.680], P = 0.725). CONCLUSION: Contemporary management of AF was associated with a low risk of ischaemic stroke. CARS and CHA2DS2-VASc score may be useful to identify high risk patients despite treatment who may benefit from more aggressive treatment and follow-up.

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey.

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.

Atrial fibrillation and stroke prevention: 25 years of research at EP Europace journal.

Stroke prevention in patients with atrial fibrillation (AF) is one pillar of the management of this common arrhythmia. Substantial advances in the epidemiology and associated pathophysiology underlying AF-related stroke and thrombo-embolism are evident. Furthermore, the introduction of the non-vitamin K antagonist oral anticoagulants (also called direct oral anticoagulants) has clearly changed our approach to stroke prevention in AF, such that the default should be to offer oral anticoagulation for stroke prevention, unless the patient is at low risk. A strategy of early rhythm control is also beneficial in reducing strokes in selected patients with recent onset AF, when compared to rate control. Cardiovascular risk factor management, with optimization of comorbidities and attention to lifestyle factors, and the patient's psychological morbidity are also essential. Finally, in selected patients with absolute contraindications to long-term oral anticoagulation, left atrial appendage occlusion or exclusion may be considered. The aim of this state-of-the-art review article is to provide an overview of the current status of AF-related stroke and prevention strategies. A holistic or integrated care approach to AF management is recommended to minimize the risk of stroke in patients with AF, based on the evidence-based Atrial fibrillation Better Care (ABC) pathway, as follows: A: Avoid stroke with Anticoagulation; B: Better patient-centred, symptom-directed decisions on rate or rhythm control; C: Cardiovascular risk factor and comorbidity optimization, including lifestyle changes.

AFA-Recur: an ESC EORP AFA-LT registry machine-learning web calculator predicting atrial fibrillation recurrence after ablation.

AIMS: Atrial fibrillation (AF) recurrence during the first year after catheter ablation remains common. Patient-specific prediction of arrhythmic recurrence would improve patient selection, and, potentially, avoid futile interventions. Available prediction algorithms, however, achieve unsatisfactory performance. Aim of the present study was to derive from ESC-EHRA Atrial Fibrillation Ablation Long-Term Registry (AFA-LT) a machine-learning scoring system based on pre-procedural, easily accessible clinical variables to predict the probability of 1-year arrhythmic recurrence after catheter ablation. METHODS AND RESULTS: Patients were randomly split into a training (80%) and a testing cohort (20%). Four different supervised machine-learning models (decision tree, random forest, AdaBoost, and k-nearest neighbour) were developed on the training cohort and hyperparameters were tuned using 10-fold cross validation. The model with the best discriminative performance on the testing cohort (area under the curve-AUC) was selected and underwent further optimization, including re-calibration. A total of 3128 patients were included. The random forest model showed the best performance on the testing cohort; a 19-variable version achieved good discriminative performance [AUC 0.721, 95% confidence interval (CI) 0.680-0.764], outperforming existing scores (e.g. APPLE score: AUC 0.557, 95% CI 0.506-0.607). Platt scaling was used to calibrate the model. The final calibrated model was implemented in a web calculator, freely available at http://afarec.hpc4ai.unito.it/. CONCLUSION: AFA-Recur, a machine-learning-based probability score predicting 1-year risk of recurrent atrial arrhythmia after AF ablation, achieved good predictive performance, significantly better than currently available tools. The calculator, freely available online, allows patient-specific predictions, favouring tailored therapeutic approaches for the individual patient.

Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole.

AIMS: To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…<1 h, 1 h…<24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. METHODS AND RESULTS: In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…<1 h, 99.6% (253/254) for episodes 1 h…<24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA2DS2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. CONCLUSION: A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p < .001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01-1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23-3.99] compared to eGFR ≥90 ml/min/1.73 m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Reflections on the usefulness of today's atrial fibrillation ablation procedure endpoints and patient-reported outcomes.

The improvement of Patient-reported outcomes, such as health-related quality of life, is the main indication for atrial fibrillation ablation. Despite this guideline derived indication for an AF ablation procedure the current standardized primary endpoint in AF ablation trials is still rhythm-related, and primarily a 30-second long AF episode. The review presents reflections on the non-rational arguments of using rhythm related endpoints rather than Patient-reported outcomes in AF ablation procedure trials despite the mismatch between many of the rhythm related variables and symptoms. Arguments for health-related quality of life as the most optimal primary endpoint in clinical trials are presented while atrial fibrillation burden is presented as the most optimal electrical complementary endpoint, apart from being the major variable in mechanistic trials.

Clinical utility and prognostic implications of the novel 4S-AF scheme to characterize and evaluate patients with atrial fibrillation: a report from ESC-EHRA EORP-AF Long-Term General Registry.

AIMS: The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. METHODS AND RESULTS: Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60-25.9], (Sb) (aHR 1.21, 95% CI: 1.08-1.35), and (Su) (aHR 1.27, 95% CI: 1.14-1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45-2.06) and (Sy) (aHR 1.29, 95% CI: 1.00-1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55-0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16-1.56). CONCLUSION: Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

Lead fixation mechanism impacts outcome of transvenous lead extraction: data from the European Lead Extraction ConTRolled Registry.

AIMS: The aims of this study is to characterize the transvenous lead extraction (TLE) population with active (A) compared with passive fixation (PFix) leads and to compare the safety, efficacy, and ease of extracting active fixation (AFix) compared with PFix right atrial (RA) and right ventricular (RV) leads. METHODS AND RESULTS: The European Lead Extraction ConTRolled Registry (ELECTRa) was analysed. Patients were divided into three groups; those with only AFix, only PFix, and combined Fix leads. Three outcomes were defined. Difficult extraction, complete radiological, and clinical success. Multivariate model was used to analyse the independent effect of Fix mechanism on these outcomes. The study included 2815 patients, 1456 (51.7%) with only AFix leads, 982 (34.9%) with only PFix leads, and 377 (13.4%) with combined Fix leads. Patients with AFix leads were younger with shorter lead dwelling time. Infection was the leading cause for TLE among the combined Fix group with lowest rates among AFix group. No difference in complications rates was noted between patients with only AFix vs. PFix leads. Overall, there were 1689 RA (1046 AFix and 643 PFix) and 2617 RV leads (1441 AFix and 1176 PFix). Multivariate model demonstrated that PFix is independently associated with more difficult extraction for both RA and RV leads, lower radiological success in the RA but has no effect on clinical success. CONCLUSION: Mechanism of Fix impact the ease of TLE of RA and RV leads and rates of complete radiological success in the RA but not clinical success. These findings should be considered during implantation and TLE procedures.

European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing: developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology.

AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing cardiac pacing. METHODS AND RESULTS: Under the auspice of the Clinical Practice Guideline Quality Indicator Committee of the European Society of Cardiology (ESC), the Working Group for cardiac pacing QIs was formed. The Group comprised Task Force members of the 2021 ESC Clinical Practice Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy, members of the European Heart Rhythm Association, international cardiac device experts, and patient representatives. We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care by constructing a conceptual framework of the management of patients receiving cardiac pacing, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. Four domains of care were identified: (i) structural framework, (ii) patient assessment, (iii) pacing strategy, and (iv) clinical outcomes. In total, seven main and four secondary QIs were selected across these domains and were embedded within the 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization therapy. CONCLUSION: By way of a standardized process, 11 QIs for cardiac pacing were developed. These indicators may be used to quantify adherence to guideline-recommended clinical practice and have the potential to improve the care and outcomes of patients receiving cardiac pacemakers.

Repolarization abnormalities unmasked with a 252-lead BSM system in patients with ARVC and healthy gene carriers.

BACKGROUND: Diagnosing arrhythmogenic right ventricular cardiomyopathy (ARVC) at an early stage can be challenging even after ECG recording and a combination of several imaging techniques. The purpose of this study was to explore if a body surface mapping (BSM) system with 252-leads could identify repolarization abnormalities and thereby diagnose early stages of ARVC. METHODS: ARVC patients, gene carriers without signs of ARVC and controls underwent a 12-lead resting ECG, signal-averaged ECG, echocardiography, 24-hours Holter monitoring, and BSM with electrocardiographic imaging (ECGI). All 252-leads, divided into four quadrants of the vest, were analyzed regarding concordances between T wave polarity and QRS main vector. RESULTS: Of 40 patients included there were 12 ARVC patients, 20 gene carriers, and 8 controls. The ARVC patients had two different repolarization patterns, one with more pronounced negative T waves at the lower left panel and another with mixed changes that clearly differed from the controls, all of whom had a normal 12 lead ECGs and consistent repolarization patterns on their BSM recordings. The patterns observed in ARVC patients were also present in 5/20 (25%) gene carriers, three of whom had normal resting ECG. A novel repolarization index successfully detected all ARVC patients and 88% of gene carriers with pathologic repolarization pattern. CONCLUSIONS: The finding that abnormal repolarization patterns could be unmasked by BSM in 25% of healthy gene carriers, suggests that it may potentially be a useful tool for identifying early manifestations of ARVC. Further and larger studies are warranted to assess its diagnostic accuracy.

Short P-Wave Duration Is Associated with Incident Atrial Fibrillation.

Atrial fibrillation (AF) is common and increases the risk for stroke and heart failure (HF). The early identification of patients at risk may prevent the development of AF and improve prognosis. This study, therefore, aimed to test the effect of the association between P-wave and PR-interval on the ECG and incident AF.The PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study (1016 individuals all aged 70 years; 50% women) was used to identify whether the ECG variables P-wave duration (Pdur) and PR-duration in lead V1 were related to new-onset AF. Exclusion criteria were prevalent AF, QRS-duration ≥ 130 milliseconds (msec), atrial tachyarrhythmias and implanted pacemaker/defibrillator. Cox proportional-hazards models were used for analyses. Adjustments were made for gender, RR-interval, beta-blocking agents, systolic blood pressure, body mass index, and smoking.Of 877 subjects at risk, 189 individuals developed AF during a 15-year follow-up. There was a U-shaped relationship between the Pdur and incident AF (P = 0.017) following multiple adjustment. Values below 60 msec were significantly associated with incident AF, with a hazard ratio of 1.55 (95% confidence interval 1.15-2.09) for a Pdur ≤ 42 msec. There was no significant relationship between incident AF and the PR-interval.A short Pdur derived from the ECG in V1 may be a useful marker for new-onset AF, enabling the early identification of at-risk patients.

The results of health-related quality of life assessment depend on the prevailing rhythm at the assessment: Experience from the CAPTAF trial (Catheter Ablation Compared with Pharmacological Therapy for Atrial Fibrillation).

AIMS: To assess whether the prevailing rhythm at the time of replying to symptom and health-related quality of life (HR-QoL) questionnaires impacts the findings. METHOD: A total of 150 patients from the randomized Catheter Ablation Compared with Pharmacological Therapy for Atrial Fibrillation-trial, comparing atrial fibrillation (AF) ablation versus drugs, were included. The effect of the prevailing rhythm on the outcome results of the HR-QoL 36-Item Short-Form Health Survey, the symptom severity questionnaire (SSQ), and the European Heart Rhythm Association (EHRA) score for classification of AF-related symptoms was assessed. RESULTS: AF as the prevailing rhythm was independently associated with a significantly lower Vitality score; 18.4 points lower (95% confidence interval -32.7 to -4.1, p = .01) compared with sinus rhythm when adjusted for AF burden, median duration of episode, number of episodes, beta-blocker use, type of AF, and sex. The presence of AF did not affect the General Health score compared with sinus rhythm, nor did it influence symptoms assessed by the SSQ or EHRA score. CONCLUSION: The observation that the presence of AF versus sinus rhythm when conducting HR-QoL tests had a negative impact on its outcome, leaving symptom-related questionnaires unaffected, implies that the prevailing rhythm should be taken into account when results of HR-QoL questionnaires are interpreted.