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.).

European Society of Cardiology: the 2023 Atlas of Cardiovascular Disease Statistics.

This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the 2021 report in presenting cardiovascular disease (CVD) statistics for the ESC member countries. This paper examines inequalities in cardiovascular healthcare and outcomes in ESC member countries utilizing mortality and risk factor data from the World Health Organization and the Global Burden of Disease study with additional economic data from the World Bank. Cardiovascular healthcare data were collected by questionnaire circulated to the national cardiac societies of ESC member countries. Statistics pertaining to 2022, or latest available year, are presented. New material in this report includes contemporary estimates of the economic burden of CVD and mortality statistics for a range of CVD phenotypes. CVD accounts for 11% of the EU's total healthcare expenditure. It remains the most common cause of death in ESC member countries with over 3 million deaths per year. Proportionately more deaths from CVD occur in middle-income compared with high-income countries in both females (53% vs. 34%) and males (46% vs. 30%). Between 1990 and 2021, median age-standardized mortality rates (ASMRs) for CVD decreased by median >50% in high-income ESC member countries but in middle-income countries the median decrease was <12%. These inequalities between middle- and high-income ESC member countries likely reflect heterogeneous exposures to a range of environmental, socioeconomic, and clinical risk factors. The 2023 survey suggests that treatment factors may also contribute with middle-income countries reporting lower rates per million of percutaneous coronary intervention (1355 vs. 2330), transcatheter aortic valve implantation (4.0 vs. 153.4) and pacemaker implantation (147.0 vs. 831.9) compared with high-income countries. The ESC Atlas 2023 report shows continuing inequalities in the epidemiology and management of CVD between middle-income and high-income ESC member countries. These inequalities are exemplified by the changes in CVD ASMRs during the last 30 years. In the high-income ESC member countries, ASMRs have been in steep decline during this period but in the middle-income countries declines have been very small. There is now an important need for targeted action to reduce the burden of CVD, particularly in those countries where the burden is greatest.

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.

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.

Effects of Atrial Fibrillation on the Human Ventricle.

RATIONALE: Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. OBJECTIVE: This study investigates the effects and molecular mechanisms of AF on the human LV. METHODS AND RESULTS: Ventricular myocardium from patients with aortic stenosis and preserved LV function with sinus rhythm or rate-controlled AF was studied. LV myocardium from patients with sinus rhythm and patients with AF showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude of LV cardiomyocytes was reduced in patients with AF, while diastolic Ca2+ levels and Ca2+ transient kinetics were not statistically different. These results were confirmed in LV cardiomyocytes from nonfailing donors with sinus rhythm or AF. Moreover, normofrequent AF was simulated in vitro using arrhythmic or rhythmic pacing (both at 60 bpm). After 24 hours of AF-simulation, human LV cardiomyocytes from nonfailing donors showed an impaired Ca2+ transient amplitude. For a standardized investigation of AF-simulation, human iPSC-cardiomyocytes were tested. Seven days of AF-simulation caused reduced systolic Ca2+ transient amplitude and sarcoplasmic reticulum Ca2+ load likely because of an increased diastolic sarcoplasmic reticulum Ca2+ leak. Moreover, cytosolic Na+ concentration was elevated and action potential duration was prolonged after AF-simulation. We detected an increased late Na+ current as a potential trigger for the detrimentally altered Ca2+/Na+-interplay. Mechanistically, reactive oxygen species were higher in the LV of patients with AF. CaMKII (Ca2+/calmodulin-dependent protein kinase IIδc) was found to be more oxidized at Met281/282 in the LV of patients with AF leading to an increased CaMKII activity and consequent increased RyR2 phosphorylation. CaMKII inhibition and ROS scavenging ameliorated impaired systolic Ca2+ handling after AF-simulation. CONCLUSIONS: AF causes distinct functional and molecular remodeling of the human LV. This translational study provides the first mechanistic characterization and the potential negative impact of AF in the absence of tachycardia on the human ventricle.

Evaluation of left ventricular and left atrial volumetric function from native MR multislice 4D flow magnitude data.

OBJECTIVES: To assess the feasibility, precision, and accuracy of left ventricular (LV) and left atrial (LA) volumetric function evaluation from native magnetic resonance (MR) multislice 4D flow magnitude images. MATERIALS & METHODS: In this prospective study, 60 subjects without signs or symptoms of heart failure underwent 3T native cardiac MR multislice 4D flow and bSSFP-cine realtime imaging. LV and LA volumetric function parameters were evaluated from 4D flow magnitude (4D flow-cine) and bSSFP-cine data using standard software to obtain end-diastolic volume (EDV), end-systolic volume (ESV), ejection-fraction (EF), stroke-volume (SV), LV muscle mass (LVM), LA maximum volume, LA minimum volume, and LA total ejection fraction (LATEF). Stroke volumes derived from both imaging methods were further compared to 4D pulmonary artery flow-derived net forward volumes (NFV). Methods were compared by correlation and Bland-Altman analysis. RESULTS: Volumetric function parameters from 4D flow-cine and bSSFP-cine showed high to very high correlations (r = 0.83-0.98). SV, LA volumes and LATEF did not differ between methods. LV end-diastolic and end-systolic volumes were slightly underestimated (EDV: -2.9 ± 5.8 mL; ESV: -2.3 ± 3.8 mL), EF was slightly overestimated (EF: 0.9 ± 2.6%), and LV mass was considerably overestimated (LVM: 39.0 ± 11.4 g) by 4D flow-cine imaging. SVs from both methods correlated very highly with NFV (r = 0.91 in both cases) and did not differ from NFV. CONCLUSION: Native multislice 4D flow magnitude data allows precise evaluation of LV and LA volumetric parameters; however, apart from SV, LV volumetric parameters demonstrate bias and need to be referred to their respective normal values. CLINICAL RELEVANCE STATEMENT: Volumetric function assessment from native multislice 4D flow magnitude images can be performed with routinely used clinical software, facilitating the application of 4D flow as a one-stop-shop functional cardiac MR exam, providing consistent, simultaneously acquired, volume and flow data. KEY POINTS: • Native multislice 4D flow imaging allows evaluation of volumetric left ventricular and atrial function parameters. • Left ventricular and left atrial function parameters derived from native multislice 4D flow data correlate highly with corresponding standard cine-derived parameters. • Multislice 4D flow-derived volumetric stroke volume and net forward volume do not differ.

State-of-the-art pulsed field ablation for cardiac arrhythmias: ongoing evolution and future perspective.

Pulsed field ablation (PFA) is an innovative approach in the field of cardiac electrophysiology aimed at treating cardiac arrhythmias. Unlike traditional catheter ablation energies, which use radiofrequency or cryothermal energy to create lesions in the heart, PFA utilizes pulsed electric fields to induce irreversible electroporation, leading to targeted tissue destruction. This state-of-the-art review summarizes biophysical principles and clinical applications of PFA, highlighting its potential advantages over conventional ablation methods. Clinical data of contemporary PFA devices are discussed, which combine predictable procedural outcomes and a reduced risk of thermal collateral damage. Overall, these technological developments have propelled the rapid evolution of contemporary PFA catheters, with future advancements potentially impacting patient care.

A computational study on the influence of antegrade accessory pathway location on the 12-lead electrocardiogram in Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White syndrome is a cardiovascular disease characterized by abnormal atrio-ventricular conduction facilitated by accessory pathways (APs). Invasive catheter ablation of the AP represents the primary treatment modality. Accurate localization of APs is crucial for successful ablation outcomes, but current diagnostic algorithms based on the 12 lead electrocardiogram (ECG) often struggle with precise determination of AP locations. In order to gain insight into the mechanisms underlying localization failures observed in current diagnostic algorithms, we employ a virtual cardiac model to elucidate the relationship between AP location and ECG morphology. We first introduce a cardiac model of electrophysiology that was specifically tailored to represent antegrade APs in the form of a short atrio-ventricular bypass tract. Locations of antegrade APs were then automatically swept across both ventricles in the virtual model to generate a synthetic ECG database consisting of 9271 signals. Regional grouping of antegrade APs revealed overarching morphological patterns originating from diverse cardiac regions. We then applied variance-based sensitivity analysis relying on polynomial chaos expansion on the ECG database to mathematically quantify how variation in AP location and timing relates to morphological variation in the 12 lead ECG. We utilized our mechanistic virtual model to showcase limitations of AP localization using standard ECG-based algorithms and provide mechanistic explanations through exemplary simulations. Our findings highlight the potential of virtual models of cardiac electrophysiology not only to deepen our understanding of the underlying mechanisms of Wolff-Parkinson-White syndrome but also to potentially enhance the diagnostic accuracy of ECG-based algorithms and facilitate personalized treatment planning.

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.

Real-world assessment of multipolar and point-by-point mapping for premature ventricular contraction ablation.

AIMS: We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS AND RESULTS: This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. CONCLUSION: The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Comparing pulsed field electroporation and radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: design and rationale of the BEAT PAROX-AF randomized clinical trial.

AIMS: Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. METHODS AND RESULTS: The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. CONCLUSION: The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.

Smartphone app-based approximation of time spent with atrial fibrillation and symptoms in patients after catheter ablation: data from the TeleCheck-AF project.

AIMS: Reduction of atrial fibrillation (AF) burden is the preferred outcome measure over categorical AF rhythm recurrence after AF ablation. In this sub-analysis of the TeleCheck-AF project, we tested the feasibility of smartphone app-based approximation of time spent with AF and/or symptoms. METHODS AND RESULTS: Patients scheduled for at least one teleconsultation during the 12-month follow-up after AF ablation were instructed to use a smartphone photoplethysmography-based application for simultaneous symptom and rhythm monitoring three times daily for 1 week. Proxies of time spent with AF and/or symptoms (% recordings, load, and % days), temporal aggregation of AF and/or symptoms (density), and symptom-rhythm correlation (SRC) were assessed. In total, 484 patients (60% male, 62 ± 9.9 years) were included. Adherence, motivation, and patient satisfaction were high. %AF recordings, AF load, and %AF days (rs = 0.88-0.95) and %symptom recordings, symptom load, and %symptom days (rs = 0.95-0.98) showed positive correlations. The SRC correlated negatively with time spent with symptoms (rs = -0.65-0.90) and with time spent with AF (rs = -0.31-0.34). In patients with paroxysmal AF before ablation and AF during the monitoring period, 87% (n = 39/44) had a low-density score <50% ('paroxysmal AF pattern') while 5% (n = 2/44) had a high-density score >90% ('persistent AF pattern'). Corresponding numbers for patients with persistent AF before ablation were 48% (n = 11/23) and 43% (n = 10/23), respectively. CONCLUSION: On-demand, app-based simultaneous rhythm and symptom assessment provides objective proxies of time spent with AF and/or symptoms and SRC, which may assist in assessing AF and symptom outcomes after AF ablation.

Bipolar radiofrequency ablation of refractory ventricular arrhythmias: results from a multicentre network.

AIMS: Advanced ablation strategies are needed to treat ventricular tachycardia (VT) and premature ventricular complexes (PVC) refractory to standard unipolar radiofrequency ablation (Uni-RFA). Bipolar radiofrequency catheter ablation (Bi-RFA) has emerged as a treatment option for refractory VT and PVC. Multicentre registry data on the use of Bi-RFA in the setting of refractory VT and PVC are lacking. The aim of this Bi-RFA registry is to determine its real-world safety, feasibility, and efficacy in patients with refractory VT/PVC. METHODS AND RESULTS: Consecutive patients undergoing Bi-RFA at 16 European centres for recurring VT/PVC after at least one standard Uni-RFA were included. Second ablation catheter was used instead of a dispersive patch and was positioned at the opposite site of the ablation target. Between March 2021 and August 2024, 91 patients underwent 94 Bi-RFA procedures (74 males, age 62 ± 13, and prior Uni-RFA range 1-8). Indications were recurrence of PVC (n = 56), VT (n = 20), electrical storm (n = 13), or PVC-triggered ventricular fibrillation (n = 2). Procedural time was 160 ± 73 min, Bi-RFA time 426 ± 286 s, and mean Uni-RFA time 819 ± 697 s. Elimination of clinical VT/PVC was achieved in 67 (74%) patients and suppression of VT/PVC in a further 10 (11%) patients. In the remaining 14 patients (15%), no effect on VT/PVC was observed. Three major complications occurred: coronary artery occlusion, atrioventricular block, and arteriovenous fistula. Follow-up lasted 7 ± 8 months. Nineteen patients (61%) remained VT free. ≥80% PVC burden reduction was achieved in 45 (78%). CONCLUSION: These real-world registry data indicate that Bi-RFA appears safe, is feasible, and is effective in the majority of patients with VT/PVC.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

Zero-fluoroscopy ablation with multielectrode pulse field ablation system: Case series.

Pulse field ablation (PFA) is a novel nonthermal ablation modality for treatment of atrial fibrillation. While mostly lacking 3D electroanatomical mapping integration, reported radiation doses in procedures using multielectrode PFA catheters are relatively high. We report a first case series of three patients where a zero-fluoroscopy approach by intracardiac echocardiography was utilized and present a possible workflow for zero-fluoroscopy ablation with the Farapulse PFA system.

Ventricular insertion site ablation of a Mahaim atriofascicular fibre in Ebstein anomaly.

Ebstein anomaly is frequently associated with accessory pathways, including Mahaim atriofascicular fibres. We herein illustrate successful Mahaim fibre ablation in Ebstein anomaly by targeting the ventricular insertion site below the tricuspid ridge.

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial. METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic flux, and targeted metabolome profiling, and immunoblots of key IGF1R downstream targets in mouse and human explanted failing and nonfailing hearts, as well. RESULTS: Young mice with increased IGF1R signaling exhibited superior cardiac function that progressively declined with aging in an accelerated fashion compared with wild-type animals, resulting in heart failure and a reduced lifespan. In contrast, mice with low cardiac IGF1R signaling exhibited inferior cardiac function early in life, but superior cardiac performance during aging, and increased maximum lifespan, as well. Mechanistically, the late-life detrimental effects of IGF1R activation correlated with suppressed autophagic flux and impaired oxidative phosphorylation in the heart. Low IGF1R activity consistently improved myocardial bioenergetics and function of the aging heart in an autophagy-dependent manner. In humans, failing hearts, but not those with compensated hypertrophy, displayed exaggerated IGF1R expression and signaling activity. CONCLUSIONS: Our findings indicate that the relationship between IGF1R signaling and cardiac health is not linear, but rather biphasic. Hence, pharmacological inhibitors of the IGF1 pathway, albeit unsuitable for young individuals, might be worth considering in older adults.

MR 4D flow-derived left atrial acceleration factor for differentiating advanced left ventricular diastolic dysfunction.

OBJECTIVES: The magnetic resonance (MR) 4D flow imaging-derived left atrial (LA) acceleration factor α was recently introduced as a means to non-invasively estimate LA pressure. We aimed to investigate the association of α with the severity of left ventricular (LV) diastolic dysfunction using echocardiography as the reference method. METHODS: Echocardiographic assessment of LV diastolic function and 3-T cardiac MR 4D flow imaging were prospectively performed in 94 subjects (44 male/50 female; mean age, 62 ± 12 years). LA early diastolic peak outflow velocity (vE), systolic peak inflow velocity (vS), and early diastolic peak inflow velocity (vD) were evaluated from 4D flow data. α was calculated from α = vE / [(vS + vD) / 2]. Mean parameter values were compared by t-test; diagnostic performance of α in predicting diastolic (dys)function was investigated by receiver operating characteristic curve analysis. RESULTS: Mean α values were 1.17 ± 0.14, 1.20 ± 0.08, 1.33 ± 0.15, 1.77 ± 0.18, and 2.79 ± 0.69 for grade 0 (n = 51), indeterminate (n = 9), grade I (n = 13), grade II (n = 13), and grade III (n = 8) LV diastolic (dys)function, respectively. α differed between subjects with non-advanced (grade < II) and advanced (grade ≥ II) diastolic dysfunction (1.20 ± 0.15 vs. 2.16 ± 0.66, p < 0.001). The area under the curve (AUC) for detection of advanced diastolic dysfunction was 0.998 (95% CI: 0.958-1.000), yielding sensitivity of 100% (95% CI: 84-100%) and specificity of 99% (95% CI: 93-100%) at cut-off α ≥ 1.58. The AUC for differentiating grade III diastolic dysfunction was also 0.998 (95% CI: 0.976-1.000) at cut-off α ≥ 2.14. CONCLUSION: The 4D flow-derived LA acceleration factor α allows grade II and grade III diastolic dysfunction to be distinguished from non-advanced grades as well as from each other. CLINICAL RELEVANCE STATEMENT: As a single continuous parameter, the 4D flow-derived LA acceleration factor α shows potential to simplify the multi-parametric imaging algorithm for diagnosis of advanced LV diastolic dysfunction, thereby identifying patients at increased risk for cardiovascular events. KEY POINTS: • Detection of advanced diastolic dysfunction is typically performed using a complex, multi-parametric approach. • The 4D flow-derived left atrial acceleration factor α alone allows accurate detection of advanced left ventricular diastolic dysfunction. • As a single continuous parameter, the left atrial acceleration factor α could simplify the diagnosis of advanced diastolic dysfunction.

Patient selection, peri-procedural management, and ablation techniques for catheter ablation of atrial fibrillation: an EHRA survey.

Catheter ablation (CA) of atrial fibrillation (AF) is the therapy of choice for the maintenance of sinus rhythm in patients with symptomatic AF. Time towards interventional treatment and peri-procedural management of patients undergoing AF ablation may vary in daily practice. The scope of this European Heart Rhythm Association (EHRA) survey was to report the current clinical practice regarding the management of patients undergoing AF ablation and physician's adherence to the European Society of Cardiology Guidelines and the EHRA/HRS/ECAS expert consensus statement on the CA for AF. This physician-based survey was conducted among EHRA members, using an internet-based questionnaire developed by the EHRA Scientific Initiatives Committee. A total of 258 physicians participated in the survey. In patients with paroxysmal or persistent AF, 42 and 9% of the physicians would routinely perform AF ablation as first-line therapy respectively, whereas 71% of physicians would consider ablation as first-line therapy in patients with symptomatic AF and left ventricular ejection fraction <35%. Only 14% of the respondents manage cardiovascular risk factors in patients referred for CA using a dedicated AF risk factor management programme. Radiofrequency CA is the preferred technology for first-time AF (56%), followed by cryo-balloon CA (40%). This EHRA survey demonstrated a considerable variation in the management of patients undergoing AF ablation in routine practice and deviations between guideline recommendations and clinical practice.

Detection of brain lesions after catheter ablation depends on imaging criteria: insights from AXAFA-AFNET 5 trial.

AIMS: Left atrial catheter ablation is well established in patients with symptomatic atrial fibrillation (AF) but associated with risk of embolism to the brain. The present analysis aims to assess the impact of diffusion-weighted imaging (DWI) slice thickness on the rate of magnetic resonance imaging (MRI)-detected ischaemic brain lesions after ablation. METHODS AND RESULTS: AXAFA-AFNET 5 trial (NCT02227550) participants underwent MRI using high-resolution (hr) DWI (slice thickness: 2.5-3 mm) and standard DWI (slice thickness: 5-6 mm) within 3-48 h after ablation. In 321 patients with analysable brain MRI (mean age 64 years, 33% female, median CHA2DS2-VASc 2), hrDWI detected at least one acute brain lesion in 84 (26.2%) patients and standard DWI in 60 (18.7%; P < 0.01) patients. High-resolution diffusion-weighted imaging detected more lesions compared to standard DWI (165 vs. 104; P < 0.01). The degree of agreement for lesion confirmation using hrDWI vs. standard DWI was substantial (κ = 0769). Comparing the proportion of DWI-detected lesions, lesion distribution, and total lesion volume per patient, there was no difference in the cohort of participants undergoing MRI at 1.5 T (n = 52) vs. 3 T (n = 269). CONCLUSION: The pre-specified AXAFA-AFNET 5 sub-analysis revealed significantly increased rates of MRI-detected acute brain lesions using hrDWI instead of standard DWI in AF patients undergoing ablation. In comparison to DWI slice thickness, MRI field strength had a no significant impact in the trial. Comparing the varying rates of ablation-related MRI-detected brain lesions across previous studies has to consider these technical parameters. Future studies should use hrDWI, as feasibility was demonstrated in the multicentre AXAFA-AFNET 5 trial.