Andrea Rossi

Aims: Atrial fibrillation (AF) is highly prevalent among cardiac amyloidosis (CA) patients and contributes significantly to their morbidity and mortality. Evidence regarding AF ablation efficacy and safety in CA patients remains limited. The aim of our study is to evaluate baseline characteristics, clinical course and outcomes of AF ablation in a series of patients with transthyretin (ATTR) or light-chain (AL) CA from a multicentre international registry. Methods and results: Patients with CA who underwent AF ablation were included. Co-primary endpoints were: (i) atrial arrhythmia (AA) recurrence; (ii) a composite endpoint of all-cause mortality and heart failure hospitalization (HFH). 109 patients (mean age 72.4 ± 7.4 years, females 17.4%, persistent AF 64.2%, ATTR 78%, AL 22%) were included. Radiofrequency, cryo-balloon and pulsed-field ablation were performed in 67%, 15% and 18% of patients, respectively; 49.5% received pulmonary vein isolation plus additional ablations. Low voltage zones were documented in 34 out of 44 patients undergoing electro-anatomical mapping (77.3%). During a median follow-up of 22.7 months, 63 patients (58.3%) experienced AA recurrence (32.4% persistent AF recurrence), with no significant differences between CA subtypes (ATTR 59.5% vs. AL 54.2%, log-rank P = 0.55). The composite endpoint of HFH and all-cause death occurred in 27 patients (25%). Recurrence of persistent AF was associated with three-fold higher risk (OR 2.9, P = 0.02) of the composite endpoint. Conclusion: CA patients undergoing AF ablation present high prevalence of persistent AF. Freedom from AA after AF ablation is achieved in 42% of patients after a two-year follow-up. Patients with persistent AF recurrence have a three-fold higher risk of HFH and death.

Background: Brugada Syndrome (BrS) is a cardiac arrhythmia associated with an increased risk of ventricular arrhythmias and sudden cardiac arrest. Although the arrhythmic substrate is traditionally localized to the ventricles, atrial fibrillation (AF) is frequently observed, suggesting a shared molecular substrate between atrial and ventricular arrhythmias. C-type natriuretic peptide (CNP) and related microRNAs (miRNAs) modulate atrial and ventricular physiology, but their roles in exosomes in BrS have not been investigated. Objectives: To investigate alterations in CNP mRNA expression and changes in the expression of selected CNP-associated miRNAs implicated in AF, both analyzed in exosomes isolated from individuals with BrS and from healthy controls. Methods: Exosomes were isolated from the plasma of BrS patients without a history of overt AF and from healthy controls. In silico analyses identified CNP-targeting miRNAs implicated in AF. Exosomal CNP and CNP-related miRNAs were analyzed using Droplet Digital PCR. Results: BrS patients exhibited a significant increase in exosomal CNP mRNA expression levels compared with controls. MiR-138-5p was selectively downregulated, whereas other AF-related CNP-targeting miRNAs (miR-4443, miR-206, miR-142-5p, miR-223-5p) showed comparable levels between groups. A positive correlation between exosomal CNP and miR-223-5p and miR-4443 suggests shared regulatory pathways. Conclusions: these findings indicate that exosomal profiling may provide a more sensitive approach than conventional circulating measurements to detect molecular remodeling in BrS. The observed alterations highlight a potential shared molecular substrate between atrial and ventricular arrhythmias and may inform future studies aimed at refining diagnostics and developing targeted therapeutic strategies.

Background: Atrial arrhythmias represent a frequent long-term complication in patients with atrial septal defects (ASDs). Interatrial block (IAB), reflecting delayed or impaired conduction across Bachmann’s bundle, has been proposed as an electrophysiological substrate predisposing to atrial arrhythmogenesis. However, evidence regarding its prevalence and clinical correlates in pediatric patients with ASD remains limited. The present study aimed to characterize interatrial conduction patterns and assess the occurrence of IAB in children with large secundum ASD undergoing percutaneous closure. Methods: Between January 2020 and March 2024, 37 consecutive pediatric patients (median age 6 years, range 5–11) with large ostium secundum ASD were included in a retrospective analysis of a prospectively maintained institutional database. Standard 12-lead electrocardiograms were recorded before and within 24 h after defect closure. P-wave morphology and duration were systematically analyzed, and IAB was classified according to the Bayés de Luna criteria. Results: The median Qp/Qs ratio was 1.69 (1.32–2.24), with a mean pulmonary artery pressure of 19 mmHg (17–22). IAB was identified in 24.3% of patients before the procedure, predominantly as first-degree IAB. Following device implantation, IAB prevalence (29.7%) and P-wave parameters remained unchanged, with no significant differences compared with baseline. No associations were observed between IAB and defect size, hemodynamic burden, or device characteristics, whereas anthropometric variables, including weight, height, and body surface area, showed a significant correlation with IAB occurrence. During a median follow-up of 199 days, no atrial arrhythmias were documented. Conclusions: In this pediatric cohort with large ASD, IAB was present in approximately one quarter of patients and appeared unrelated to anatomical or procedural factors, supporting the hypothesis of an underlying congenital conduction abnormality. Early recognition of IAB may therefore have implications for long-term arrhythmic risk stratification in this population.

BACKGROUND: Retrograde ethanolization of the vein of Marshall (VOM) has been identified as an adjunct technique in the treatment of persistent atrial fibrillation (AF) and left atrial tachycardia, as stated in the last consensus statement on ablation of AF. However, there is a lack of high-volume data on the technique. METHODS: Through the collection of data from worldwide centers, we performed this international survey that aims to analyze the safety and procedural characteristics of VOM ethanolization in patients referred for treatment of AF or left atrial tachycardia. RESULTS: We included 5579 patients (66 years; range, 20–93) from 26 centers, who underwent VOM ethanolization between 2008 and 2024 for persistent AF (81%), paroxysmal AF (9%), or left atrial tachycardia (10%) under deep sedation (53%) or general anesthesia (47%). A concomitant mitral isthmus line was attempted in 79% of the cases, achieving mitral isthmus block in 98% of patients. There were 0.92% of periprocedural serious adverse events, including 0.09% of peri-procedural death (5 patients). Three patients developed hemodynamic collapse immediately after VOM ethanolization, causing the death of 1 due to anaphylactic shock. One patient died following surgical drainage of pericardial effusion 3 weeks after the procedure. The 3 other deaths were not directly related to VOM ethanolization. Pericardial effusion was observed in 123 patients (2.2%) at the time of or immediately after the procedure, requiring drainage in 20 patients (0.36%) and later in 32 additional patients (0.57%), including 5 (0.09%) requiring drainage. Pacemaker implantation was required in 2 patients (0.04%), 1 for high-grade atrioventricular block and 1 for sinus node dysfunction. CONCLUSIONS: This international survey shows that VOM ethanolization is predominantly performed in patients with persistent AF. It is associated with rare but potentially life-threatening adverse events. Mitral isthmus line ablation results in a very high rate of block when performed concomitantly.

Background/Objectives: Patient-reported outcome after treatment is an important factor that positively correlates with the quality of care and can influence the patient’s future health choices. Both radiofrequency ablation (RFA) and cryoballoon ablation (CBA) are effective techniques for pulmonary vein isolation in patients with atrial fibrillation (AF) and have shown similar results in efficacy and safety, but they have not been thoroughly compared in terms of patient satisfaction. The aim of this study is to assess the satisfaction of paroxysmal AF patients who underwent RFA and CBA after their first procedure. Methods: Consecutive patients who underwent their first procedure of pulmonary vein isolation with RFA or CBA in eight international centres were included. A ten-point Likert scale was used for measuring patient-reported outcomes, evaluating anxiety before procedure, pain during and after ablation, motivation to repeat the procedure in future if necessary, and real and perceived procedural time. Results: A total of 483 patients were enrolled. Median age was 63 [56–69] years, and 281 (58.1%) patients were men. In total, 385 (79.7%) patients underwent RFA and 98 (20.3%) underwent CBA. RFA and CBA were equivalent in terms of the satisfaction of the patient, with the only exception being groin pain, which was lower in the CBA group (2 [0–3] vs. 3 [1–4], p = 0.002). Conscious sedation was used in 414 (86.7%) patients and general anaesthesia in 69 (14.3%) patients. The use of general anaesthesia reduced the perceived pain during and after the procedure in both techniques (p < 0.05), but it resulted in lower pre-procedural anxiety only in RFA patients compared to those under conscious sedation (4 [2–6] vs. 5 [3–7], p = 0.007). Anaesthetic management alone did not affect the willingness to repeat the procedure in RFA patients, while CBA patients under general anaesthesia were more motivated to repeat the procedure than those under conscious sedation (10 [8–10] vs. 7 [6–8], p < 0.001). The perceived procedure time was shorter than the actual time in all settings. Conclusions: Anaesthetic management seems to have a greater impact on patient-reported outcome than the technique used during ablation. Despite this, patients most motivated to repeat the procedure were those who underwent CBA under general anaesthesia.

Brugada syndrome (BrS) is a cardiac disease associated with characteristic ECG abnormalities and a heightened risk of sudden cardiac death, especially in young individuals with structurally normal hearts. The primary aim of this study was to highlight, for the first time, the potential of using droplet digital PCR (ddPCR), a highly sensitive method, to detect C-type natriuretic peptide (CNP) and its receptors, NPR-B and NPR-C, expression in BrS. Whole-blood samples from 12 subjects with type 1 BrS and 12 controls were analyzed. CNP expression was detectable and lower in BrS patients than in the controls, although not significantly. NPR-B and NPR-C expression was significantly reduced in the same patients (p ≤ 0.05). Strong correlations were observed between CNP and NPR-B (p = 0.01) and NPR-C (p < 0.0001), as well as between NPR-B and NPR-C (p = 0.0002). Body weight correlated with CNP (p = 0.02), NPR-B (p = 0.03), and NPR-C (p = 0.02); meanwhile, NPR-B expression was related to height (p = 0.05). This study is the first to analyze CNP expression and its specific receptors using ddPCR technology, showing for the first time their presence and activation in individuals with BrS. Although further research is needed to clarify CNP-related mechanisms, these findings offer a valuable starting point for exploring its role in BrS.

Brugada Syndrome (BrS) is a primary electrical epicardial disease characterized by ST-segment elevation followed by a negative T-wave in the right precordial leads on the surface electrocardiogram (ECG), also known as the ‘type 1’ ECG pattern. The risk stratification of asymptomatic individuals with spontaneous type 1 ECG pattern remains challenging. Clinical and electrocardiographic prognostic markers are known. As none of these predictors alone is highly reliable in terms of arrhythmic prognosis, several multi-factor risk scores have been proposed for this purpose. This article presents a new workflow for processing endocardial signals acquired with high-density RV electro-anatomical mapping (HDEAM) from BrS patients. The workflow, which relies solely on Matlab software, calculates various electrical parameters and creates multi-parametric maps of the right ventricle. The workflow, but it has already been employed in several research studies involving patients carried out by our group, showing its potential positive impact in clinical studies. Here, we will provide a technical description of its functionalities, along with the results obtained on a BrS patient who underwent an endocardial HDEAM.

Background: Ablation failures are common in case of intramural location of the arrhythmogenic substrate. Case summary: We report the case of a patient with cardiomyopathy contributed by frequent monomorphic ventricular arrhythmias (VAs) from intramural basal interventricular septum treated with double-balloon venous ethanol ablation (VEA) after a previous failed endocardial radiofrequency (RF) ablation. Discussion: Double-balloon VEA represents a safe and effective therapeutic option in case of intramural VAs also in the absence of venous collaterals joining selectively an intramural arrhythmic substrate.