Pasquale Notarstefano

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.

Ventricular tachycardia (VT) remains a major cause of morbidity and mortality in patients with structural heart disease. While catheter ablation has become a cornerstone in VT management, recurrence rates remain substantial due to limitations in electroanatomic mapping (EAM), particularly in cases of deep or heterogeneous arrhythmogenic substrates. Cardiac imaging, especially when multimodal and integrated with mapping systems, has emerged as a critical adjunct to enhance procedural efficacy, safety, and individualized strategy. This comprehensive review explores the evolving role of various imaging modalities, including echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), and intracardiac echocardiography (ICE), in the preprocedural and intraprocedural phases of VT ablation. We highlight their respective strengths in substrate identification, anatomical delineation, and real-time guidance. While limitations persist, including costs, availability, artifacts in device carriers, and lack of standardization, future advances are likely to redefine procedural workflows.

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.

To investigate the prognostic significance of heterogeneity in the refractoriness of right ventricular (RV) outflow tract (RVOT) and RV apex at the electrophysiological study (EPS) in Brugada syndrome (BrS). A cohort of BrS patients (primary prevention) from five Italian centres was retrospectively analysed. Patients with spontaneous or drug-induced Type-1 electrocardiogram (ECG) + symptoms were offered an EPS for prognostic stratification. The primary endpoint was a composite of sudden cardiac death (SCD), resuscitated cardiac arrest, or appropriate intervention by the implantable cardioverter-defibrillator (ICD). Three hundred and seventy-two patients with BrS were evaluated (44 ± 15 years, 69% males, 23% with ICD): 4 SCDs and 17 ICD interventions occurred at follow-up (median 48, interquartile range: 36–60 months). Family history of SCD, syncope, and a spontaneous Type-1 ECG pattern were univariate predictors of the primary endpoint in the whole population. In patients undergoing EPS (n = 198, 53%, 44 ± 12 years, 71% males, 39% with ICD), 3 SCD and 15 ICD interventions occurred at follow-up. In this subset, the primary endpoint was not only predicted by ventricular tachycardia/fibrillation inducibility but also by a difference in the refractory period between RVOT and RV apex (ΔRP_RVOT-apex) >60 ms. ΔRP_RVOT-apex > 60 ms remained an independent predictor of SCD/ICD shock at bivariate analysis, even when adjusted for the other univariate predictors, showing the highest predictive power at C-statistic analysis (0.75, 95% confidence interval 0.63–0.86). Heterogeneity of RV refractory periods is a strong, independent predictor of life-threatening arrhythmias in BrS patients, beyond VT/VF inducibility at EPS and common clinical predictors. In patients with Type-1 ECG Brugada pattern, the presence of an increased difference in the refractoriness between the right ventricular outflow tract (RVOT) and the apex, mainly driven by an increased refractory period in the RVOT, increases the prognostic discrimination power of the electrophysiological study, currently based only on inducibility of life-threatening arrhythmias. BrS, Brugada syndrome; EPS, electrophysiological study; RP, refractory period; RV, right ventricle; RVOT, right ventricular outflow tract; VF, ventricular fibrillation; VT, ventricular tachycardia.

The aim of this survey, which was open to all Italian cardiologists involved in arrhythmia, was to assess common practice regarding sedation and analgesia in interventional electrophysiology procedures in Italy. The survey consisted of 28 questions regarding the approach to sedation used for elective direct-current cardioversion (DCC), subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, atrial fibrillation (AF) ablation, ventricular tachycardia (VT) ablation, and transvenous lead extraction procedures. A total of 105 cardiologists from 92 Italian centres took part in the survey. The rate of centres where DCC, S-ICD implantation, AF ablation, VT ablation and lead extraction procedures were performed without anaesthesiologic assistance was 60.9%, 23.6%, 51.2%, 37.3%, and 66.7%, respectively. When these procedures were performed without anaesthesiologic assistance, the drugs (in addition to local anaesthetics) commonly administered were benzodiazepines (from 64.3% to 79.6%), opioids (from 74.4% to 88.1%), and general anaesthetics (from 7.1% to 30.4%). Twenty-three (21.9%) of the 105 cardiologists declared that they routinely administered propofol, without the supervision of an anaesthesiologist, in at least one of the above-mentioned procedures. In current Italian clinical practice, there is a lack of uniformity in the sedation/analgesia approach used in interventional electrophysiology procedures.

Aims: Radiofrequency catheter ablation (RFCA) represents an effective option for idiopathic premature ventricular contractions (PVCs) treatment. Ablation Index (AI) is a novel ablation marker incorporating RF power, contact force, and time of delivery into a single weighted formula. Data regarding AI-guided PVCs RFCA are currently lacking. Aim of the study was to compare AI-guided and standard RFCA outcomes in patients with PVCs originating from the right ventricle outflow tract (RVOT). Methods and results: Consecutive patients undergoing AI-guided RFCA of RVOT idiopathic PVCs were prospectively enrolled. Radiofrequency catheter ablation was performed following per-protocol target cut-offs of AI, depending on targeted area (RVOT free wall AI cut-off: 590; RVOT septum AI cut-off: 610). A multi-centre cohort of propensity-matched (age, sex, ejection fraction, and PVC site) patients undergoing standard PVCs RFCA was used as a comparator. Sixty AI-guided patients (44.2 ± 18.0 years old, 58% male, left ventricular ejection fraction 56.2 ± 3.8%) were enrolled; 34 (57%) were ablated in RVOT septum and 26 (43%) patients in the RVOT free wall area. Propensity match with 60 non-AI-guided patients was performed. Acute outcomes and complications resulted comparable. At 6 months, arrhythmic recurrence was more common in non-AI-guided patients whether in general (28% vs. 7% P = 0.003) or by ablated area (RVOT free wall: 27% vs. 4%, P = 0.06; RVOT septum 29% vs. 9% P = 0.05). Ablation Index guidance was associated with improved survival from arrhythmic recurrence [overall odds ratio 6.61 (1.95–22.35), P = 0.001; RVOT septum 5.99 (1.21–29.65), P = 0.028; RVOT free wall 11.86 (1.12–124.78), P = 0.039]. Conclusion: Ablation Index-guidance in idiopathic PVCs ablation was associated with better arrhythmic outcomes at 6 months of follow-up.

Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS.