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<span class="paragraphSection"><strong>This editorial refers to ‘Dronedarone provides effective early rhythm control: post-hoc analysis of the ATHENA trial using EAST-AFNET 4 criteria’ by P. Kirchhof <span style="font-style:italic;">et al.</span>, <a href="https://doi.org/10.1093/europace/euaf080">https://doi.org/10.1093/europace/euaf080</a>.</strong></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Cardiac magnetic resonance (CMR) imaging for tissue characterization offers valuable insights for risk stratification among patients with cardiomyopathy. This study aimed to assess the prognostic value of CMR-based tissue characterization in predicting response to cardiac resynchronization therapy (CRT) in patients with non-ischaemic cardiomyopathy (NICM).<div class="boxTitle">Methods and results</div>Retrospective analysis was performed on CMR data from NICM patients before CRT implantation. Various CMR parameters, including the late gadolinium enhancement (LGE), native T1, T2, and extracellular volume (ECV), were analysed. Among the 101 patients (mean age: 66 years, male: 52.5%), 72 (71.3%) were CRT responders. The CRT responders had lower LGE burden (13.1 vs. 35.3%, <span style="font-style:italic;">P</span> < 0.001), native T1 (1334.5 vs. 1371.6 ms, <span style="font-style:italic;">P</span> = 0.012), T2 (42.2 vs. 45.7 ms, <span style="font-style:italic;">P</span> < 0.001), and ECV (30.8 vs. 36.8%, <span style="font-style:italic;">P</span> < 0.001) compared with CRT non-responders. After adjusting for other risk factors, LGE burden ≤ 20% [odds ratio (OR): 22.61, 95% confidence interval (CI): 4.73–176.68, <span style="font-style:italic;">P</span> < 0.001], ECV ≤ 34% (OR: 15.93, 95% CI: 3.01–115.13, <span style="font-style:italic;">P</span> = 0.002), and T2 ≤ 45 ms (OR: 8.10, 95% CI: 1.82–43.75, <span style="font-style:italic;">P</span> = 0.008) were identified as predictors of good CRT response and favourable clinical outcomes (log-rank <span style="font-style:italic;">P</span> < 0.001).<div class="boxTitle">Conclusion</div>Cardiac magnetic resonance-based tissue parameters effectively predict CRT response and clinical outcomes in patients with NICM, independently of conventional predictors.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Steam pops present a significant concern during radiofrequency (RF) ablation of atrial fibrillation (AF). It is crucial to analyse the incidence and ablation characteristics associated with steam pops. This study aims to investigate the occurrence and potential predictors of steam pops.<div class="boxTitle">Methods and results</div>This study included 3263 patients with AF who underwent RF ablation. Patients with paroxysmal AF received bilateral circumferential pulmonary vein (PV) ablation, while those with persistent AF underwent additional linear ablation. The ablation parameters at the sites of steam pops were compared to those at adjacent anatomical locations. A total of 81 steam pops (2.5%) with one pericardial tamponade were recorded. Steam pops were observed at liner ablation sites: 6 (0.4%) at the mitral isthmus, 16 (0.9%) at the tricuspid isthmus (CTI), and 7 (0.5%) along the roofline. The most common sites of steam pops were the anterior edge of the left superior PV and the inferior vena cava side of the CTI. The impedance drop was significantly higher (18.2 ± 9.5 Ω vs. 13.5 ± 4.8 Ω, <span style="font-style:italic;">P</span> < 0.001) at steam pop sites. The optimal cut-off points of impedance drop for predicting steam pops were > 9.5 Ω within the first 3 s, > 10.5 Ω within the first 5 s, > 13.5 Ω within the first 10 s, and > 18.5 Ω in the whole ablation, respectively.<div class="boxTitle">Conclusion</div>The incidence of steam pops during ablation of AF is infrequent. Impedance drop is the only ablation parameter that could predict the occurrence of steam pops.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Previous studies have not examined the role of non-electrical myocardial disease substrates in determining the optimal atrio-ventricular delay (AVD) settings. We conducted virtual patient simulations to evaluate whether myocardial disease substrates influence the acute response to AVD optimization at rest and during exercise.<div class="boxTitle">Methods and results</div>The CircAdapt cardiovascular model was used to simulate various left ventricular (LV) remodelling found in cardiac resynchronization therapy candidates. We simulated electrical dyssynchrony, LV dilatation with preserved and reduced contractility, and increased LV passive stiffness. We simulated cardiac resynchronization following biventricular (BiVP) and non-selective LBB pacing (nsLBBP). The paced-AVD ranged from 220 to 40 ms. Cardiac output and heart rate were increased to simulate different levels of exercise. The optimal AVD was the one leading to the highest stroke volume (SV) and the lowest mean left atrial pressure (mLAP). At rest, in simulations with healthy myocardium the gain in SV by AVD optimization was larger compared to those with reduced contractility and stiff myocardium. However, mLAP was comparably decreased by AVD optimization in both healthy and diseased myocardium. During exercise, the optimal AVD shifted to shorter values, and mLAP was more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium.<div class="boxTitle">Conclusion</div>Simulations show that hypocontractility and stiffness reduce the effect of AVD optimization on SV but enhance its benefit in lowering mLAP. Notably, virtual patients with stiff ventricles experience greater benefits from AVD optimization during exercise compared to resting conditions. Furthermore, nsLBBP provides more favourable improvements in mLAP than BiVP.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Obesity is a significant risk factor for atrial fibrillation (AF), but the mechanisms by which obesity contributes to AF are not fully understood. Recent studies have indicated that the Stimulator of Interferon Genes (STING) signalling, mediated by mitochondrial damage, plays a crucial role in cardiac remodelling in various metabolic and cardiovascular diseases. This study aims to explore the role of STING in obesity-mediated AF and its potential mechanisms.<div class="boxTitle">Methods and results</div>In this study, rats were divided into four groups: two groups received tail vein injections of AAV9-cTnT-STING siRNA and were fed either a normal diet or a high-fat diet (HFD) for 12 weeks; the other two groups received injections of AAV9-cTnT-NC siRNA and were similarly fed either a normal diet or a HFD. The atrial STING signalling, AF vulnerability, electrical remodelling, and substrate remodelling were assessed in all groups. Results showed that the induction of AF was increased in obese rats, accompanied by severe mitochondrial damage and upregulation of the STING inflammatory signalling cascade. STING activation was associated with atrial fibrosis, cardiomyocyte apoptosis, and substrate remodelling, including alterations in the gap junction protein CX40 and ion channels. Additionally, STING was linked to excessive calcium transfer from the endoplasmic reticulum to the mitochondria. Knockdown of STING prevented AF vulnerability and both electrical and substrate remodelling in obese rats.<div class="boxTitle">Conclusion</div>Mitochondrial damage-mediated activation of the STING signalling pathway promotes obesity-induced atrial remodelling and the occurrence of AF.</span>
<span class="paragraphSection"><strong>This editorial refers to ‘Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial’ by M. Rienstra <span style="font-style:italic;">et al</span>., <a href="https://doi.org/10.1093/europace/euaf064">https://doi.org/10.1093/europace/euaf064</a>.</strong></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The pharmacological provocation test is a pivotal tool in cardiac electrophysiology for the diagnosis of potential causes of sudden cardiac death, sudden cardiac arrest (SCA), arrhythmias, symptoms, or ECG abnormalities. The 2022 European Society of Cardiology Guidelines for the Treatment of Ventricular Arrhythmias and Prevention of Sudden Cardiac Death offered guidance on provocation testing but did not describe the indications and requirements in depth. This clinical consensus statement, led by the European Heart Rhythm Association and approved by major international stakeholders, aims to advise the general cardiologist and the arrhythmia expert who to test and when, where, and how to do it. The statement focuses on current practice for the diagnosis of subclinical arrhythmia syndromes and the causes of SCA, building upon the recommendations of the Guidelines. We address the sodium channel blocker provocation test for patients suspected of Brugada syndrome as well as the use of epinephrine, isoproterenol, adenosine, ergonovine, and acetylcholine.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Epicardial access during electrophysiology procedures offers valuable insights and therapeutic options for managing ventricular arrhythmias (VAs). The current clinical consensus statement on epicardial VA ablation aims to provide clinicians with a comprehensive understanding of this complex clinical scenario. It offers structured advice and a systematic approach to patient management. Specific sections are devoted to anatomical considerations, criteria for epicardial access and mapping evaluation, methods of epicardial access, management of complications, training, and institutional requirements for epicardial VA ablation. This consensus is a joint effort of collaborating cardiac electrophysiology societies, including the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, the Latin American Heart Rhythm Society, and the Canadian Heart Rhythm Society.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Pulsed field ablation (PFA) is a growing ablation modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients. This study assesses the 6-month safety and effectiveness of a novel balloon-in-basket, mapping-integrated PFA system, with a purpose-built form factor for PVI.<div class="boxTitle">Methods and results</div>The VOLT CE Mark Study is a prospective, multi-center, pre-market study. A total of 150 patients with drug-refractory paroxysmal (PAF) or persistent AF (PersAF) were enrolled between 8 November 2023 and 14 March 2024, of which 146 patients (age 64.1 ± 10.0 years, 63.0% male, 70.5% PAF) underwent PVI with the balloon-in-basket PFA catheter and system featuring integrated electroanatomic mapping with contact-sensing. Study endpoints were the rate of primary serious adverse events within 7 days as well as acute procedural effectiveness and 6-month freedom from recurrence. Acute effectiveness was achieved in 99.1% (573/578) of treated PVs (98.6% of patients, 144/146) with 17.6 ± 5.7 PFA applications/patient. Procedure, fluoroscopy, LA dwell, and transpired ablation times were 100.4 ± 33.0, 17.3 ± 12.1, 39.4 ± 20.6, and 31.4 ± 16.8 min, respectively. There were 4 (2.7%; 4/146) primary serious adverse events. The rate of freedom from documented atrial arrhythmias was 88.2% in PAF patients and 76.7% in PersAF patients (freedom from symptomatic recurrence was documented in 90.2% of PAF patients and 74.4% of PersAF patients) through 6-months post-index procedure.<div class="boxTitle">Conclusion</div>The VOLT CE Mark Study primary results demonstrate the safety and effectiveness of the novel balloon-in-basket PFA system to perform PVI in PAF and PersAF.</span>
<span class="paragraphSection">Catheter ablation has become a cornerstone in the management of atrial fibrillation (AF), offering an effective rhythm control strategy for patients with drug-refractory disease.<sup><a href="#euaf065-B1" class="reflinks">1</a></sup> While thermal ablation techniques—radiofrequency (RF) and cryoablation—have demonstrated strong clinical outcomes, they are associated with procedural limitations, including the risk of collateral damage to surrounding structures such as the oesophagus and phrenic nerves, as well as the potential to induce pulmonary vein stenosis.<sup><a href="#euaf065-B1" class="reflinks">1</a></sup> Pulsed field ablation (PFA) has emerged as a novel, non-thermal alternative, with the potential to deliver precise myocardial ablation while minimizing adverse effects.<sup><a href="#euaf065-B2" class="reflinks">2</a></sup></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Despite increasing prevalence, the general population lacks knowledge regarding diagnosis, implications, and management of cardiac arrhythmias (CA). This study aims to assess public perception of CA and identify knowledge gaps.<div class="boxTitle">Methods and results</div>The 36-item <span style="font-style:italic;">PULSE</span> survey was disseminated via social media to the general population and conducted under the auspices of the European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) with EHRA patient committee support. Among 3924 participants (2177 healthy, 1747 with previously diagnosed CA; 59% female, 90% European), 81% reported fear of CA. Females were more likely to be ‘very’ or ‘moderately afraid’ than males [odds ratio (OR) 1.159 (1.005, 1.337), <span style="font-style:italic;">P</span> = 0.046]. While most recognized complications of CA—heart failure (82%), stroke (80%), and death (75%)—43% were unaware that CA can be asymptomatic. Those with cardiopulmonary resuscitation (CPR) training in the past 5 years were 2.6 times and 4.7 times more confident identifying sudden cardiac death and initiating CPR (<span style="font-style:italic;">P</span> < 0.001). Confidence was lower in retired participants [OR 0.574 (0.499, 0.660), <span style="font-style:italic;">P</span> < 0.001] and Southern Europeans [OR 0.703 (0.600, 0.824), <span style="font-style:italic;">P</span> < 0.001]. Without CPR training, only 15% felt confident initiating CPR. Among CA participants, 28% reported severe to disabling daily symptoms. Males were more often asymptomatic (20% vs. 9%, <span style="font-style:italic;">P</span> < 0.001). Treatment rates were comparable between sex categories (81% vs. 79%, <span style="font-style:italic;">P</span> = 0.413). Interdisciplinary shared decision-making processes were reported by 4%. Notably, 1 in 10 CA cases was self-diagnosed using a wearable device, and 30% of CA participants used smartwatches for self-monitoring.<div class="boxTitle">Conclusion</div>Significant knowledge gaps regarding CA exist in the general population. Targeted educational initiatives could be a viable tool to enhance public knowledge, confidence in detecting and managing arrhythmias, particularly for women, who experience greater fear and symptom severity despite similar treatment rates.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Conduction system pacing (CSP) is being increasingly adopted as a more physiological alternative to right ventricular and biventricular pacing. Since the 2021 European Society of Cardiology pacing guidelines, there has been growing evidence that this therapy is safe and effective. Furthermore, left bundle branch area pacing was not covered in these guidelines due to limited evidence at that time. This Clinical Consensus Statement provides advice on indications for CSP, taking into account the significant evolution in this domain.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Lifestyle and risk factor modification (LRFM) forms a central pillar in the management of atrial fibrillation (AF). This European Heart Rhythm Association (EHRA) survey aims to assess current clinical practice regarding LRFM across EHRA countries.<div class="boxTitle">Methods and results</div>A 31-item questionnaire was developed and distributed amongst healthcare professionals via the EHRA and social media, between 23 September and 21 October 2024. Of 258 respondents from 28 countries, 39.9% reported that their healthcare system is badly or very badly designed to deliver meaningful LRFM. Risk factors that respondents felt least confident managing included psychological distress (42.2% of respondents not confident), sleep-disordered breathing (33.8%), and obesity (22.4%). Respondents estimated that 70% of patients with AF at their institution may benefit from exercise-based cardiac rehabilitation but that only 10% are referred for this. The most important barrier to cardiac rehabilitation in AF was identified as local programmes not accepting patients with AF only (42.1% of respondents). Despite 37.7% of respondents using a body mass index cut-off when deciding on catheter ablation suitability (with a mean cut-off of 36.7 ± 5.4 kg/m<sup>2</sup>), only 23.5% of patients with obesity are referred for formal dietary advice. Lack of patient motivation or engagement was identified as the most important barrier to weight loss (41.3% of respondents). Moreover, 89.6% of respondents routinely assess their patient's alcohol intake, whilst only 23.9% systemically assess for psychological distress and 16.5% for sleep-disordered breathing.<div class="boxTitle">Conclusion</div>Delivering comprehensive LRFM in AF poses significant challenges. Improvements to healthcare infrastructures are required to successfully implement meaningful LRFM.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. New treatments are needed to cardiovert recent-onset paroxysmal AF quickly and safely. RESTORE-1 was a multicentre, randomized, double-blind, placebo-controlled trial of a 120 mg orally inhaled solution of flecainide acetate (FlecIH-103) for cardioversion of symptomatic, recent-onset (≤48 h) paroxysmal AF. The study aim was to evaluate the efficacy and safety of FlecIH-103 administered via oral inhalation.<div class="boxTitle">Methods and results</div>Patients experiencing a recent-onset paroxysmal AF episode were randomized to receive a single dose of FlecIH-103 or placebo delivered over two 3.5 min inhalation periods, while patients were monitored using 12-lead electrocardiograms and Holter. The trial was stopped prematurely after treating 55 patients, due to lower-than-expected conversion rates and plasma levels. Mean age was 59.6 years, 31.5% of patients were female, and 59.2% were having their first AF episode. Conversion rate was 30.8% (95% confidence interval: 14.7–43.8) for the active group (<span style="font-style:italic;">n</span> = 39) and 0.0% for the placebo group (<span style="font-style:italic;">n</span> = 12) (<span style="font-style:italic;">P</span> = 0.04). Median time to conversion was 12.8 min (IQR: 17.2). In the active group, the mean flecainide plasma level was 198 ng/mL (SD: 156), which is ∼50% lower than in the previous studies. The most common adverse events (AEs) were dysgeusia, dyspnoea, and cough. All AEs were short-lasting and of mild or moderate intensity.<div class="boxTitle">Conclusion</div>Despite early termination of the trial, FlecIH-103 was significantly more effective than placebo in cardioverting AF. Safety data did not show any serious AEs. Further studies of FlecIH-103 are needed to optimize the combination of drug formulation and inhalation delivery platform.<div class="boxTitle">Clinical trial registration</div>URL: <a href="https://clinicaltrials.gov">https://clinicaltrials.gov</a>, unique identifier: NCT05039359</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>The Lead EvaluAtion for Defibrillation and Reliability (LEADR) trial evaluated the small-diameter (4.7 Fr), integrated bipolar OmniaSecure defibrillation lead. As previously reported, the trial exceeded primary safety and efficacy objective thresholds, demonstrating favourable performance and zero fractures through ∼12 months follow-up, with patients in ongoing follow-up. Longer-term follow-up of the LEADR trial with emphasis on the sensing and detection capabilities of the OmniaSecure lead is reported here.<div class="boxTitle">Methods and results</div>Patients with indications for <span style="font-style:italic;">de novo</span> implantable cardioverter-defibrillators/cardiac resynchronisation therapy defibrillators were implanted with the OmniaSecure lead in standard right ventricle (RV) locations and followed at pre-specified intervals along with CareLink™ remote monitoring transmissions, where available. Throughout follow-up, the lead was evaluated for safety, efficacy, and reliability along with sensing and detection performance. There were 643/657 (97.9%) patients successfully implanted with the OmniaSecure lead with mean follow-up of 18.2 ± 5.5 months. There was a 96.9% freedom from major study lead-related complications at 24 months. Inappropriate shock rate was 2.7 and 3.8% at 12 and 24 months, respectively. At 24 months, 17.6% of patients received appropriate therapies (shock and/or ATP) with a 76.5% ATP efficacy. There have been zero fractures during follow-up along with chronically stable pacing capture threshold, pacing impedance, and R-wave amplitudes. There were four patients with an adverse event related to PWOS (0.6%), none of which was associated with inappropriate shock. There were four patients with an adverse event related to TWOS (0.6%), of which three patients were associated with inappropriate shock (0.5%). Oversensing was resolved predominantly by programming the RV sensitivity to less sensitive settings. During VF induction at implant, 97.6% (120/123) of patients showed appropriate VF episode detection at the least sensitive setting of 1.2 mV, with the remaining having detection at more sensitive settings. In follow-up, 670 VT/VF episodes were appropriately detected and treated in 94 patients with a variety of RV sensitivities and no reports of under-detected episodes. Moreover, a virtual sensitivity analysis also showed no under-detection across different RV sensitivity programming.<div class="boxTitle">Conclusion</div>Chronic sensing performance of the OmniaSecure defibrillation lead demonstrated R-wave stability with a low rate of P-wave and T-wave oversensing, resolved predominantly by adjusting RV sensitivity. Further, VT/VF detection was successful and was not impacted when programmed to less sensitive settings. The OmniaSecure lead shows robust sensing and detection performance and programmability in ongoing follow-up.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>We studied the blood pressure (BP) decrease after carotid sinus massage to study cardioinhibition (CI) and arterial vasodepression (aVD), whether CI and aVD occur independent of one another, and how the BP decrease ends.<div class="boxTitle">Methods and results</div>We measured BP, heart rate (HR), stroke volume, and total peripheral resistance (TPR) retrospectively in carotid sinus massage cohorts in two Dutch syncope centres. Cardioinhibition and aVD were defined as HR and TPR decreasing below 3 SD under pre-massage baseline means. We used the logratio method to analyse changes relative to baseline and tested whether CI and aVD occurred together more often than through chance and whether the responses depended on massage duration and on corrective BP increases. Cardioinhibition occurred in 48% and aVD in 30% of 244 massages of 90 persons. Cardioinhibition and aVD did not occur together more often than randomly. Compared with aVD, CI occurred more often, earlier, faster, and shorter with a larger maximal but similar overall BP-decreasing effect. Longer massage duration yielded a larger BP decrease through stronger aVD. The BP decrease evoked corrective increases of HR and TPR.<div class="boxTitle">Conclusion</div>Cardioinhibition appears as a phasic response to the onset of massage, independent of aVD, which is a more latent response sensitive to ongoing massage. Blood pressure corrections probably depend on the contralateral carotid sinus and aortic baroreceptors. The BP decrease after sinus massage may in part depend on the efficacy of corrective responses.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Arrhythmic burden after discharge in patients with new-onset persistent left bundle branch block (NOP-LBBB) following transcatheter aortic valve replacement (TAVR) with Evolut devices remains largely unknown. The aim of this study is to assess the incidence and type of arrhythmias at 2-year follow-up in patients with NOP-LBBB post-TAVR.<div class="boxTitle">Methods and results</div>This is a prospective multicentre study including 88 patients with LBBB persisting for ≥3 days post-implantation. Before discharge, an implantable loop recorder (REVEAL XT/LINQ) was implanted; patients had continuous monitoring for 2 years. Arrhythmic events were adjudicated in a central core lab. Of the arrhythmic events, 411 were detected in 58 patients [65.9%; 2 (1–4) events per patient]. Symptoms were reported in 12/58 (20.7%), and therapy was changed in 25/58 (43.1%). There were 101 bradyarrhythmic events in 33 patients [35 high-grade atrioventricular block (HAVB) and 66 severe bradycardia]. The HAVB incidence was higher in the early (4-week) phase and remained stable over time, whereas severe bradycardia increased after 1 year. Permanent pacemaker was required in 11 (12.5%) patients (6.8% and 5.7% in the first and second year, respectively). There were 310 tachyarrhythmic events in 29 patients (120 AF/AFL, 111 AT, 72 SVT, 6 NSVT, and 1 VT); its incidence decreased throughout the 2 years. New AF/AFL episodes occurred in 20/69 patients [29%; symptomatic in 2/20 (10%)].<div class="boxTitle">Conclusion</div>Patients with NOP-LBBB post-TAVR with Evolut devices exhibited a high burden of late arrhythmias, with events occurring in two-thirds of patients and leading to treatment changes in about half of them. These data should inform future studies on cardiac monitoring devices for follow-up and treatment optimization in this challenging population.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Patients with left ventricular assist devices (LVADs) are at high risk for ventricular tachycardia (VT), and data on VT ablation in patients with LVAD are scarce. This multicentre registry assessed the mechanism of VT, procedural parameters, and outcome of VT ablation in patients with LVAD (NCT06063811).<div class="boxTitle">Methods and results</div>Data of patients with LVAD referred for VT ablation at nine tertiary care centres were collected retrospectively. Parameters included VT mechanisms, procedural data, VT recurrence, and mortality. Overall, 69 patients (90% male, mean age 60.7 ± 8.4 years) undergoing 72 ablation procedures were included. Most procedures were conducted after intensification of antiarrhythmic drug (AAD) treatment (18/72; 25%) or a prior combination of ≥2 AADs (31/72; 43%). Endocardial low-voltage areas were detected in all patients. The predominant VT mechanism was scar-related re-entry (76/96 VTs; 79%), and 19/96 VTs (20%) were related to the LVAD cannula. Non-inducibility of any VT was achieved in 28/72 procedures (39%). No LVAD-related complication was observed. The extent of endocardial scar was associated with VT recurrence. The median follow-up was 283 days (interquartile range 70–587 days). A total of 3/69 patients were lost to follow-up, 10/69 (14%) were transplanted, 26/69 (38%) died, and 16/69 (23%) patients were free from VT.<div class="boxTitle">Conclusion</div>Although often a last resort, VT ablation in patients with LVAD is feasible and safe when performed in experienced centres. These patients suffer from a high scar burden, and cardiomyopathy-associated rather than cannula-related scar seems to be the dominant substrate. Ventricular tachycardia recurrence is high despite extensive treatment, and the overall prognosis is limited.</span>
<span class="paragraphSection">We read with great interest the article by de Lange <span style="font-style:italic;">et al</span>.<sup><a href="#euaf058-B1" class="reflinks">1</a></sup> on carotid sinus massage (CSM) and that CSM requires ‘re-implementation’ in clinical practice in patients with syncope, cardiovascular autonomic dysfunction (CVAD), and arrhythmias. We would like to comment on several aspects.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Adherence to an ideal cardiovascular health (CVH) might contribute to lower the burden of sudden cardiac death (SCD) in the community. We aimed to examine the association between the number of ideal CVH metrics at baseline and of its change over 10 years with the risk of SCD.<div class="boxTitle">Methods and results</div>The Copenhagen City Heart Study is a community-based prospective cohort study. The number of ideal CVH metrics (range 0–6; non-smoking and ideal level of body mass index, physical activity, untreated glucose, untreated systolic blood pressure, and untreated total cholesterol levels) at baseline in 1991–94 and its 10-year change thereof between 1981–83 and 1991–94 were evaluated. Definite SCD was defined as a death occurring within 1 h (eye-witnessed case) or within 24 h (non-eye–witnessed) of symptoms onset, with the presence of confirmed ventricular tachycardia and the exclusion of non-cardiac cause at autopsy. Fine and Gray sub-distribution HRs (sHRs) were calculated to account for competing risk. The study population includes 8837 participants (57% women; mean age 57 years, ±15 years) in 1991–94. After a median follow-up of 22.6 years from 1 January 1993 up to 31 December 2016, 56 definite SCD occurred. The risk of definite SCD decreased gradually with the number of ideal metrics in 1991–94 [sHR = 0.58; 95% confidence interval (CI): 0.44–0.75 per additional ideal metric] and with the change (i.e. improvement) in the number of ideal metrics between 1981–83 and 1991–94 (sHR = 0.68; 0.50–0.93 per change in the number of ideal metrics). Effect size was lower for coronary death, all-cause mortality, and coronary heart disease events.<div class="boxTitle">Conclusion</div>Adherence to a higher number of ideal cardiovascular health was related to a substantial lower risk of definite SCD.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Pre-procedural imaging can facilitate scar-related ventricular tachycardia (VT) ablation, although only limited data have been reported. This prospective registry aimed to analyse procedural data and outcomes in a multi-centre setting of a pre-defined VT ablation strategy facilitated by the integration of pre-procedural imaging into the navigation system.<div class="boxTitle">Methods and results</div>Consecutive patients referred for scar-related left-sided VT ablation were prospectively enrolled at five European tertiary hospitals. Pre-procedural cardiac magnetic resonance (CMR)–derived scar maps and/or multi-detector computed tomography (MDCT)–derived wall thinning maps of the left ventricle (LV) were obtained and integrated into the navigation system. An endocardial or endoepicardial approach was chosen based on the scar distribution at pre-procedural imaging. The decision of performing a detailed electro-anatomical map (EAM) of the LV (image-aided) or to using the pre-procedural imaging for guiding the ablation without obtaining an EAM (image-guided) was left to the physician’s discretion. One hundred and seventy-one patients (71% with ischaemic cardiomyopathy) were included. Cardiac magnetic resonance was integrated in 159 (93%), MDCT in 113 (66%), and both in 101 (59%) procedures. Procedure-related complications occurred in 9 (5%) patients. At a mean follow-up of 18 ± 19 months, the overall survival and VT recurrence-free survival were 91 and 74.4%, respectively. There were no significant differences in long-term ablation outcomes based on the type of cardiomyopathy (<span style="font-style:italic;">P</span> = 0.88) or the pre-procedural imaging modality employed (<span style="font-style:italic;">P</span> = 0.33). An image-guided approach appears feasible, safe, and faster, with reduced procedure, radiofrequency, and fluoroscopy times, without compromising efficacy.<div class="boxTitle">Conclusion</div>In a large multi-centre prospective cohort, VT ablation facilitated by pre-procedural imaging is associated with favourable long-term outcomes.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>The clinical spectrum of cardiac implantable electronic device (CIED) infections includes isolated pocket infection (IPI), pocket infection complicated by infective endocarditis (PIRIE), and lead-related infective endocarditis (LRIE). The aim of this study was to assess the risk factors, clinical course, and outcomes in patients with CIED infections and to demonstrate differences between PIRIE and LRIE.<div class="boxTitle">Methods and results</div>The retrospective analysis of data from 3847 patients undergoing transvenous lead extraction for non-infectious (2640; 68.62%) and infectious (1207; 31.38%) indications, including 361 (29.91%) IPI, 472 (39.11%) PIRIE, and 374 (30.99%) LRIE, showed some differences in risk factors, clinical course, and outcomes between the subgroups. Unlike PIRIE, diabetes [hazard ratio (HR) = 1.488; 95% confidence interval (CI; 1.178–1.879), <span style="font-style:italic;">P</span> < 0.001] and lead abrasion [HR = 2.117; 95% CI (1.665–2.691), <span style="font-style:italic;">P</span> < 0.001] increased the risk of LRIE. The risk of pocket infection spread was greater with <span style="font-style:italic;">Staphylococcus aureus</span> infection [HR = 1.596; 95% CI (1.202–2.120), <span style="font-style:italic;">P</span> < 0.001]. Compared with LRIE, patients with PIRIE had lower levels of inflammatory markers and lower prevalence of vegetations. Mortality in PIRIE compared with LRIE patients was lower (53.18 vs. 62.30%; <span style="font-style:italic;">P</span> < 0.001) and comparable to IPI (50.69%; <span style="font-style:italic;">P</span> = 0.162) at long-term [median 1828 (815–3139) days] follow-up.<div class="boxTitle">Conclusion</div>Cardiac implantable electronic device infections share common risk factors; however, diabetes and intra-cardiac lead abrasion predispose to LRIE, whereas multiple leads and <span style="font-style:italic;">S. aureus</span> in pocket culture are risk factors for pocket infection spread. Compared with LRIE, the clinical course of PIRIE was milder, and short- and long-term mortalities were lower, but comparable with IPI after >1 year. This may be an argument in favour of categorization into primary LRIE and secondary endocarditis, i.e. PIRIE.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Advanced technologies such as charge density mapping (CDM) show promise in guiding adjuvant ablation in patients with persistent atrial fibrillation (AF); however, their limited availability restricts widespread adoption. We sought to determine whether regions of the left atrium containing CDM-identified pivoting and rotational propagation patterns during AF could also be reliably identified using more conventional contact mapping techniques.<div class="boxTitle">Methods and results</div>Twenty-two patients undergoing <span style="font-style:italic;">de novo</span> ablation of persistent AF underwent both CDM and electroanatomic voltage mapping during AF and sinus rhythm with multiple pacing protocols. Through the use of a left atrium statistical shape model, the location of distinctive propagation patterns identified by CDM was compared with low-voltage areas (LVAs) and regions of slow conduction velocity (CV). Neither LVA nor CV mapping during paced rhythms reliably identified regions containing CDM propagation patterns. Conduction velocity mapping during AF did correlate with these regions (ρ = −0.63, <span style="font-style:italic;">P</span> < 0.0001 for pivoting patterns; ρ = −0.54, <span style="font-style:italic;">P</span> < 0.0001 for rotational patterns). These propagation patterns consistently occurred in two specific anatomical regions across patients: the anteroseptal and inferoposterior walls of the left atrium.<div class="boxTitle">Conclusion</div>Mapping techniques during paced rhythms do not reliably correspond with regions of CDM-identified propagation patterns in persistent AF. However, these propagation patterns are consistently observed in two specific anatomical regions, suggesting a predisposition to abnormal electrophysiological properties. While further research is needed, these regions may serve as promising targets for empirical ablation, potentially reducing the reliance on complex mapping techniques.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>Genome-wide association studies (GWASs) identified common single-nucleotide polymorphisms (SNPs) in more than 100 genomic regions associated with atrial fibrillation (AF). We aimed to identify novel AF genes in Taiwanese population by multi-stage GWAS.<div class="boxTitle">Methods and results</div>In exploratory stage, we did GWAS with whole-genome genotypes (4 512 191 SNPs) in 516 patients with AF from the National Taiwan University AF Registry and 5160 normal sinus rhythm controls from the Taiwan Biobank. Significant loci were replicated in 1002 independent patients and 2003 controls and in the UK Biobank. Expression quantitative trait locus (eQTL) mapping and transcriptome-wide association study (TWAS) were performed to implicate functional significance. Stage I GWAS revealed three loci associated with AF with a genome-wide significance level, including one close to <span style="font-style:italic;">PITX2</span> gene (chromosome 4q25, rs2723329, minor allele frequency [MAF] 0.50 vs. 0.41, <span style="font-style:italic;">P</span> = 1.53 × 10<sup>−10</sup>), another close to <span style="font-style:italic;">RAP1A</span> gene (also to previous <span style="font-style:italic;">KCND3</span>; chromosome 1p13.2, rs7525578, MAF 0.17 vs. 0.07, <span style="font-style:italic;">P</span> = 1.24 × 10<sup>−26</sup>), and one novel locus close to <span style="font-style:italic;">HNF4G</span> gene (chromosome 8q21.13, rs2980218, MAF 0.44 vs. 0.35, <span style="font-style:italic;">P</span> = 2.19 × 10<sup>−9</sup>). They were validated in Stage II population. The eQTL analyses showed significant colocalization of 1p13.2 locus with <span style="font-style:italic;">RAP1A</span> gene expression in fibroblasts and 8q21.13 locus with <span style="font-style:italic;">HNF4G</span> expression in lymphocytes. There is a significant association of <span style="font-style:italic;">RAP1A</span> gene expression in fibroblasts and <span style="font-style:italic;">HNF4G</span> in lymphocytes and brain with AF in TWAS.<div class="boxTitle">Conclusion</div>Genome-wide association study in Taiwan revealed <span style="font-style:italic;">PITX2</span> and <span style="font-style:italic;">RAP1A/KCND3</span> loci and novel AF locus (<span style="font-style:italic;">HNF4G</span>) with the most significant locus in the <span style="font-style:italic;">RAP1A</span> locus. <span style="font-style:italic;">RAP1A</span> and <span style="font-style:italic;">HNF4G</span> genes may implicate fibrosis, metabolic, and neurogenic pathways in pathogenesis of AF.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>The aim of this study was to perform an external validation of an automatic machine learning (ML) algorithm for heart rhythm diagnostics using smartphone photoplethysmography (PPG) recorded by patients with atrial fibrillation (AF) and atrial flutter (AFL) pericardioversion in an unsupervised ambulatory setting.<div class="boxTitle">Methods and results</div>Patients undergoing cardioversion for AF or AFL performed 1-min heart rhythm recordings pericardioversion at least twice daily for 4–6 weeks, using an iPhone 7 smartphone running a PPG application (CORAI Heart Monitor) simultaneously with a single-lead electrocardiogram (ECG) recording (KardiaMobile). The algorithm uses support vector machines to classify heart rhythm from smartphone-PPG. The algorithm was trained on PPG recordings made by patients in a separate cardioversion cohort. Photoplethysmography recordings in the external validation cohort were analysed by the algorithm. Diagnostic performance was calculated by comparing the heart rhythm classification output to the diagnosis from the simultaneous ECG recordings (gold standard). In total, 460 patients performed 34 097 simultaneous PPG and ECG recordings, divided into 180 patients with 16 092 recordings in the training cohort and 280 patients with 18 005 recordings in the external validation cohort. Algorithmic classification of the PPG recordings in the external validation cohort diagnosed AF with sensitivity, specificity, and accuracy of 99.7%, 99.7% and 99.7%, respectively, and AF/AFL with sensitivity, specificity, and accuracy of 99.3%, 99.1% and 99.2%, respectively.<div class="boxTitle">Conclusion</div>A machine learning-based algorithm demonstrated excellent performance in diagnosing atrial fibrillation and atrial flutter from smartphone-PPG recordings in an unsupervised ambulatory setting, minimizing the need for manual review and ECG verification, in elderly cardioversion populations.<div class="boxTitle">Clinical Trial Registration</div><a href="http://Clinicaltrials.gov">Clinicaltrials.gov</a>, NCT04300270</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Aims</div>The aim of this study was to examine differences in incidence rates of all-cause mortality (ACM) and sudden cardiac death (SCD) in persons of differing socio-economic position (SEP).<div class="boxTitle">Methods and results</div>All deaths in Denmark from 1 January to 31 December 2010 (1 year) were included. Autopsy reports, death certificates, discharge summaries, and nationwide health registries were reviewed to identify cases of SCD. Socio-economic position was measured as either household income or highest achieved educational level and analysed separately. Hazard rates were calculated using univariate and multivariable Cox regression models adjusting for age, sex, and selected comorbidities. A total of 53 452 deaths were included, of which 6820 were classified as SCDs. Incidence rates of ACM and SCD increased with age and were higher in the lower SEP groups. The greatest difference in SCD incidence was found between the low and high education level groups, with an incidence rate ratio of 5.1 (95% confidence interval 3.8–6.8). The hazard ratios for ACM and SCD were significantly higher for low SEP groups, independent of comorbidities. Compared with the highest income group, the low-income group had adjusted hazard ratios of ACM and SCD that were 2.17 (2.01–2.34) and 1.72 (1.67–1.76), respectively.<div class="boxTitle">Conclusion</div>We observed an inverse association between both income and education level and the risk of ACM and SCD in the general population, which persisted independently of baseline comorbidities. Our results indicate a need for further research into the mechanisms behind socio-economic disparities in healthcare and targeted preventative strategies.</span>
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