Low-Voltage Area Ablation in Addition to Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52-0.81, p < 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] -5.32 min, 95% CI -19.01-8.46 min, p = 0.45), fluoroscopy time (MD -1.10 min, 95% CI -2.48-0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40-1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate.

Glucagon-like peptide-1 receptor agonist semaglutide reduces atrial fibrillation incidence: A systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are new anti-hyperglycaemic drugs with proven cardiovascular (CV) benefit in diabetic and non-diabetic patients at high CV risk. Despite a neutral class effect on arrhythmia risk, data on semaglutide suggest a possible drug-specific benefit in reducing atrial fibrillation (AF) occurrence. OBJECTIVE: To perform a meta-analysis of randomized clinical trials (RCTs) to assess the risk of incident AF in patients treated with semaglutide compared to placebo. METHODS AND RESULTS: Ten RCTs were included in the analysis. Study population encompassed 12,651 patients (7285 in semaglutide and 5366 in placebo arms), with median follow-up of 68 months. A random effect meta-analytic model was adopted to pool relative risk (RR) of incident AF. Semaglutide reduces the risk of AF by 42% (RR .58, 95% CI .40-.85), with low heterogeneity across the studies (I2 0%). At subgroup analysis, no differences emerged between oral and subcutaneous administration (oral: RR .53, 95% CI .23-1.24, I2 0%; subcutaneous: RR .59, 95% CI .39-.91, I2 0%; p-value .83). In addition, meta-regression analyses did not show any potential influence of baseline study covariates, in particular the proportion of diabetic patients (p-value .14) and body mass index (BMI) (p-value .60). CONCLUSIONS: Semaglutide significantly reduces the occurrence of incident AF by 42% as compared to placebo in individuals at high CV risk, mainly affected by type 2 diabetes mellitus. This effect appears to be consistent independently of the route of administration of the drug (oral or subcutaneous), the presence of underlying diabetes and BMI.

The Ablate-by-LAWT multicentre prospective study: Personalized paroxysmal atrial fibrillation ablation with ablation index adapted to local left atrial wall thickness.

BACKGROUND: Personalized radiofrequency (RF) ablation for paroxysmal atrial fibrillation (PAF), adapting the ablation index (AI) to local left atrial wall thickness (LAWT), proved to be highly efficient maintaining high arrhythmia-free survival rates. However, multicentre data are lacking. This multicentre, prospective, non-randomized study was conducted at 5 tertiary hospitals and sought to assess the safety, efficacy, and reproducibility of the LAWT-guided ablation for PAF. METHODS: Consecutive patients referred for first-time PAF were prospectively enrolled. The LAWT maps were obtained from preprocedural multidetector computed tomography and integrated into the navigation system. AI was titrated according to the local LAWT, and the ablation line was personalized to avoid the thickest regions while encircling the pulmonary veins (PVs). RESULTS: A total 109 patients (60.1 ± 9.4 years, 64.2% male) were enrolled. Median procedure time was 61.7 min (48.4-83.8), fluoroscopy time was 1.0 min (0.4-3.3), and RF time was 13.9 min (12.3-16.8). Median AI tailored to the local LAWT was 393 (374-412) for the anterior wall and 340 (315-378) for the posterior wall. Right and left PVs first-pass isolation was achieved in 89% and 91.7% of the patients, respectively. At 12-month follow-up, freedom from any atrial arrhythmia was 93.4% (95% CI 88.7-98.1), without differences across centres (P = 0.169). One patient experienced femoral artery pseudoaneurysm, with no other serious procedural-related complication. CONCLUSION: The Ablate-by-LAWT study proved that LAWT-guided PV isolation for PAF is safe, effective, and efficient in a multicentre setting. Twelve-month recurrence-free survival exceeded 90% (NCT04218604).

Cardioneuroablation for vasovagal syncope: insights on patients' selection, centre settings, procedural workflow and endpoints-results from an European Heart Rhythm Association survey.

AIMS: Cardioneuroablation (CNA) is a catheter-based intervention for recurrent vasovagal syncope (VVS) that consists in the modulation of the parasympathetic cardiac autonomic nervous system. This survey aims to provide a comprehensive overview of current CNA utilization in Europe. METHODS AND RESULTS: A total of 202 participants from 40 different countries replied to the survey. Half of the respondents have performed a CNA during the last 12 months, reflecting that it is considered a treatment option of a subset of patients. Seventy-one per cent of respondents adopt an approach targeting ganglionated plexuses (GPs) systematically in both the right atrium (RA) and left atrium (LA). The second most common strategy (16%) involves LA GP ablation only after no response following RA ablation. The procedural endpoint is frequently an increase in heart rate. Ganglionated plexus localization predominantly relies on an anatomical approach (90%) and electrogram analysis (59%). Less utilized methods include pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Post-CNA, anticoagulation or antiplatelet therapy is prescribed, with only 11% of the respondents discharging patients without such medication. Cardioneuroablation is perceived as effective (80% of respondents) and safe (71% estimated <1% rate of procedure-related complications). Half view CNA emerging as a first-line therapy in the near future. CONCLUSION: This survey offers a snapshot of the current implementation of CNA in Europe. The results show high expectations for the future of CNA, but important heterogeneity exists regarding indications, procedural workflow, and endpoints of CNA. Ongoing efforts are essential to standardize procedural protocols and peri-procedural patient management.

Automatic and interpretable prediction of the site of origin in outflow tract ventricular arrhythmias: machine learning integrating electrocardiograms and clinical data.

The treatment of outflow tract ventricular arrhythmias (OTVA) through radiofrequency ablation requires the precise identification of the site of origin (SOO). Pinpointing the SOO enhances the likelihood of a successful procedure, reducing intervention times and recurrence rates. Current clinical methods to identify the SOO are based on qualitative analysis of pre-operative electrocardiograms (ECG), heavily relying on physician's expertise. Although computational models and machine learning (ML) approaches have been proposed to assist OTVA procedures, they either consume substantial time, lack interpretability or do not use clinical information. Here, we propose an alternative strategy for automatically predicting the ventricular origin of OTVA patients using ML. Our objective was to classify ventricular (left/right) origin in the outflow tracts (LVOT and RVOT, respectively), integrating ECG and clinical data from each patient. Extending beyond differentiating ventricle origin, we explored specific SOO characterization. Utilizing four databases, we also trained supervised learning models on the QRS complexes of the ECGs, clinical data, and their combinations. The best model achieved an accuracy of 89%, highlighting the significance of precordial leads V1-V4, especially in the R/S transition and initiation of the QRS complex in V2. Unsupervised analysis revealed that some origins tended to group closer than others, e.g., right coronary cusp (RCC) with a less sparse group than the aortic cusp origins, suggesting identifiable patterns for specific SOOs.

Personalized pulmonary vein isolation with very high-power short-duration lesions guided by left atrial wall thickness: the QDOT-by-LAWT randomized trial.

AIMS: Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using very high-power short-duration (vHPSD) radiofrequency (RF) ablation proved to be safe and effective. However, vHPSD applications result in shallower lesions that might not be always transmural. Multidetector computed tomography-derived left atrial wall thickness (LAWT) maps could enable a thickness-guided switching from vHPSD to the standard-power ablation mode. The aim of this randomized trial was to compare the safety, the efficacy, and the efficiency of a LAWT-guided vHPSD PVI approach with those of the CLOSE protocol for PAF ablation (NCT04298177). METHODS AND RESULTS: Consecutive patients referred for first-time PAF ablation were randomized on a 1:1 basis. In the QDOT-by-LAWT arm, for LAWT ≤2.5 mm, vHPSD ablation was performed; for points with LAWT > 2.5 mm, standard-power RF ablation titrating ablation index (AI) according to the local LAWT was performed. In the CLOSE arm, LAWT information was not available to the operator; ablation was performed according to the CLOSE study settings: AI ≥400 at the posterior wall and ≥550 at the anterior wall. A total of 162 patients were included. In the QDOT-by-LAWT group, a significant reduction in procedure time (40 vs. 70 min; P < 0.001) and RF time (6.6 vs. 25.7 min; P < 0.001) was observed. No difference was observed between the groups regarding complication rate (P = 0.99) and first-pass isolation (P = 0.99). At 12-month follow-up, no significant differences occurred in atrial arrhythmia-free survival between groups (P = 0.88). CONCLUSION: LAWT-guided PVI combining vHPSD and standard-power ablation is not inferior to the CLOSE protocol in terms of 1-year atrial arrhythmia-free survival and demonstrated a reduction in procedural and RF times.

MSA-VT Score for Assessment of Long-Term Prognosis after Electrical Storm Ablation.

INTRODUCTION: Prognosis after electrical storm (ES) ablation remains severe, especially in patients with recurrent sustained monomorphic ventricular tachycardia (SMVT) or progressive heart failure (HF). However, single-factor-based prediction is suboptimal and may be refined by more complex algorithms. We sought to evaluate if a novel score MSA-VT (M = moderate/severe mitral regurgitation, S = severe HF at admission, A = atrial fibrillation at admission, VT = inducible SMVT after ablation) may improve prediction of death and recurrences compared to single factors and previous scores (PAINESD, RIVA and I-VT). METHODS: A total of 101 consecutive ES ablation patients were retrospectively analyzed over a 32.8-month (IQR 10-68) interval. The MSA-VT score was calculated as the sum of the previously mentioned factors' coefficients based on hazard ratio values in Cox regression analysis. The AUC for death prediction by MSA-VT was 0.84 (p < 0.001), superior to PAINESD (AUC 0.63, p = 0.03), RIVA (AUC 0.69, p = 0.02) and I-VT (0.56, p = 0.3). MSA-VT ≥ 3 was associated with significantly higher mortality during follow-up (52.7%, p < 0.001). CONCLUSIONS: Prediction by single factors and previously published scores after ES ablation may be improved by the novel MSA-VT score; however, this requires further external validation in larger samples.

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. METHODS AND RESULTS: We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. CONCLUSION: Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

Ablación por cateter de radiofrecuencia de extrasístoles ventriculares con origen en el seno coronario izquierdo

Las extrasístoles ventriculares (EEVV) son frecuentemente asintomáticas y no requieren de tratamiento antiarrítmico. Las EEVV de los tractos de salida son las EEVV idiopáticas más frecuentes en la práctica clínica. La anamnésis, el examen físico y el electrocardiograma son fundamentales en el diagnóstico. Aunque las EEVV de los tractos de salidas ventriculares son consideradas benignas, pueden producir diversos síntomas y desencadenar una cardiomiopatía inducida por las extrasístoles, que lleva a un deterioro de la función sistólica ventricular izquierda y en última instancia, insuficiencia cardiaca. Cuando el tratamiento farmacológico de las EEVV fracasa, nos queda la ablación de arritmias por catéter de radiofrecuencia como única alternativa eficaz. Este es el caso de la paciente de sexo femenino de 62 años, hipertensa, dislipidémica y tabaquista, que demuestra la seguridad de la ablación por catéter de radiofrecuencia, la eficacia terapéutica, y el restablecimiento integro de la función ventricular del corazón.

Premature ventricular complexes (PVC) are frequently asymptomatic and do not require antiarrhythmic treatment. Outflow tract PVC are the most common idiopathic PVC in clinical practice. The anamnesis, physical examination and electrocardiogram are essential in the diagnosis of these patients. Although PVC of the ventricular outflow tracts are considered benign, they can produce various symptoms such as dyspnea on exertion, asthenia, palpitations, dizziness, presyncope or syncope, and in those patients with very high arrhythmic burden (>24% on a 24-hour Holter monitoring), can trigger extrasystole-induced cardiomyopathy, leading to deterioration of left ventricular systolic function and ultimately heart failure. When pharmacological treatment of PVC fails, ablation of arrhythmias by radiofrequency catheter is the only effective alternative. This is the case of the 62-year-old female patient, hypertensive, dyslipidemic and a smoker, which demonstrates the safety of radiofrequency catheter ablation, the therapeutic efficacy, and the complete restoration of the ventricular function of the heart.

Functional mapping to reveal slow conduction and substrate progression in atrial fibrillation.

AIMS: The aim of our study was to analyse the response to short-coupled atrial extrastimuli to identify areas of hidden slow conduction (HSC) and their relationship with the atrial fibrillation (AF) phenotype. METHODS AND RESULTS: Twenty consecutive patients with paroxysmal AF and persistent AF (10:10) underwent the first pulmonary vein isolation procedure. Triple short-coupled extrastimuli were delivered in sinus rhythm (SR), and the evoked response was analysed: sites exhibiting double or highly fragmented electrograms (EGM) were defined as positive for HSC (HSC+). The delta of the duration of the bipolar EGM was analysed, and bipolar EGM duration maps were built. High-density maps were acquired using a multipolar catheter during AF, SR, and paced rhythm. Spatial co-localization of HSC+ and complex fractionated atrial EGMs (CFAE) during AF was evaluated. Persistent AF showed a higher number and percentage of HSC+ than paroxysmal AF (13.9% vs. 3.3%, P < 0.001). The delta of EGM duration was 53 ± 22 ms for HSC+ compared with 13 ± 11 (10) ms in sites with negative HSC (HSC-) (P < 0.001). The number and density of HSC+ were lower than CFAE during AF (19 vs. 56 per map, P < 0.001). The reproducibility and distribution of HSC+ in repeated maps were superior to CFAE (P = 0.19 vs. P < 0.001). Sites with negative and positive responses showed a similar bipolar voltage in the preceding sinus beat (1.65 ± 1.34 and 1.48 ± 1.47 mV, P = 0.12). CONCLUSION: Functional mapping identifies more discrete and reproducible abnormal substrates than mapping during AF. The HSC+ sites in response to triple extrastimuli are more frequent in persistent AF than in paroxysmal AF.

Assessing left atrial intramyocardial fat infiltration from computerized tomography angiography in patients with atrial fibrillation.

AIMS: Epicardial adipose tissue might promote atrial fibrillation (AF) in several ways, including infiltrating the underlying atrial myocardium. However, the role of this potential mechanism has been poorly investigated. The aim of this study is to evaluate the presence of left atrial (LA) infiltrated adipose tissue (inFAT) by analysing multi-detector computer tomography (MDCT)-derived three-dimensional (3D) fat infiltration maps and to compare the extent of LA inFAT between patients without AF history, with paroxysmal, and with persistent AF. METHODS AND RESULTS: Sixty consecutive patients with AF diagnosis (30 persistent and 30 paroxysmal) were enrolled and compared with 20 age-matched control; MDCT-derived images were post-processed to obtain 3D LA inFAT maps for all patients. Volume (mL) and mean signal intensities [(Hounsfield Units (HU)] of inFAT (HU -194; -5), dense inFAT (HU -194; -50), and fat-myocardial admixture (HU -50; -5) were automatically computed by the software. inFAT volume was significantly different across the three groups (P = 0.009), with post-hoc pairwise comparisons showing a significant increase in inFAT volume in persistent AF compared to controls (P = 0.006). Dense inFAT retained a significant difference also after correcting for body mass index (P = 0.028). In addition, more negative inFAT radiodensity values were found in AF patients. Regional distribution analysis showed a significantly higher regional distribution of LA inFAT at left and right superior pulmonary vein antra in AF patients. CONCLUSION: Persistent forms of AF are associated with greater degree of LA intramyocardial adipose infiltration, independently of body mass index. Compared to controls, AF patients present higher LA inFAT volume at left and right superior pulmonary vein antra.

Twenty-five years of research in cardiac imaging in electrophysiology procedures for atrial and ventricular arrhythmias.

Catheter ablation is nowadays considered the treatment of choice for numerous cardiac arrhythmias in different clinical scenarios. Fluoroscopy has traditionally been the primary imaging modality for catheter ablation, providing real-time visualization of catheter navigation. However, its limitations, such as inadequate soft tissue visualization and exposure to ionizing radiation, have prompted the integration of alternative imaging modalities. Over the years, advancements in imaging techniques have played a pivotal role in enhancing the safety, efficacy, and efficiency of catheter ablation procedures. This manuscript aims to explore the utility of imaging, including electroanatomical mapping, cardiac computed tomography, echocardiography, cardiac magnetic resonance, and nuclear cardiology exams, in helping electrophysiology procedures. These techniques enable accurate anatomical guidance, identification of critical structures and substrates, and real-time monitoring of complications, ultimately enhancing procedural safety and success rates. Incorporating advanced imaging technologies into routine clinical practice has the potential to further improve clinical outcomes of catheter ablation procedures and pave the way for more personalized and precise ablation therapies in the future.

Bayesian analysis of the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia trial.

BACKGROUND AND AIMS: Bayesian analyses can provide additional insights into the results of clinical trials, aiding in the decision-making process. We analysed the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia (SURVIVE-VT) trial using Bayesian survival models. METHODS AND RESULTS: The SURVIVE-VT trial randomized patients with ischaemic cardiomyopathy and monomorphic ventricular tachycardia (VT) to catheter ablation or antiarrhythmic drugs (AAD) as a first-line strategy. The primary outcome was a composite of cardiovascular death, appropriate implantable cardioverter-defibrillator shocks, unplanned heart failure hospitalizations, or severe treatment-related complications. We used informative, skeptical, and non-informative priors with different probabilities of large effects to compute the posterior distributions using Markov Chain Monte Carlo methods. We calculated the probabilities of hazard ratios (HR) being <1, <0.9, and <0.75, as well as 2-year survival estimates. Of the 144 randomized patients, 71 underwent catheter ablation and 73 received AAD. Regardless of the prior, catheter ablation had a >98% probability of reducing the primary outcome (HR < 1) and a >96% probability of achieving a reduction of >10% (HR < 0.9). The probability of a >25% (HR < 0.75) reduction of treatment-related complications was >90%. Catheter ablation had a high probability (>93%) of reducing incessant/slow undetected VT/electric storm, unplanned hospitalizations for ventricular arrhythmias, and overall cardiovascular admissions > 25%, with absolute differences of 15.2%, 21.2%, and 20.2%, respectively. CONCLUSION: In patients with ischaemic cardiomyopathy and VT, catheter ablation as a first-line therapy resulted in a high probability of reducing several clinical outcomes compared to AAD. Our study highlights the value of Bayesian analysis in clinical trials and its potential for guiding treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03734562.

Clinical impact of aging on outcomes of cardioneuroablation for reflex syncope or functional bradycardia: Results from the cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs-The ELEGANCE multicenter study.

BACKGROUND: Cardioneuroablation (CNA) is a novel treatment for reflex syncope. The effect of aging on CNA efficacy is not fully understood. OBJECTIVE: The purpose of this study was to assess the impact of aging on candidacy and efficacy of CNA for treating vasovagal syncope (VVS), carotid sinus syndrome (CSS), and functional bradyarrhythmia. METHODS: The ELEGANCE (cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs) multicenter study assessed CNA in patients with reflex syncope or severe functional bradyarrhythmia. Patients underwent pre-CNA Holter electrocardiography (ECG), head-up tilt testing (HUT), and electrophysiological study. CNA candidacy and efficacy was assessed in 14 young (18-40 years), 26 middle-aged (41-60 years), and 20 older (>60 years) patients. RESULTS: Sixty patients (37 men; mean age 51 ± 16 years) underwent CNA. The majority (80%) had VVS, 8% had CSS, and 12% had functional bradycardia/atrioventricular block. Pre-CNA Holter ECG, HUT, and electrophysiological findings did not differ across age groups. Acute CNA success was 93%, without differences between age groups (P = .42). Post-CNA HUT response was negative in 53%, vasodepressor in 38%, cardioinhibitory in 7%, and mixed in 2%, without differences across age groups (P = .59). At follow-up (8 months, interquartile range 4-15), 53 patients (88%) were free of symptoms. Kaplan-Meier curves did not show differences in event-free survival between age groups (P = .29). The negative predictive value of a negative HUT was 91.7%. CONCLUSION: CNA is a viable treatment for reflex syncope and functional bradyarrhythmia in all ages, and is highly effective in mixed VVS. HUT is a key step in postablation clinical assessment.