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2. Posterior wall isolation in patients with persistent atrial fibrillation: a single center comparative study between ablation index and very high power short duration radiofrequency ablation protocol

Author

Ciconte, G, primary, Negro, G, additional, Boccellino, A, additional, Rondine, R, additional, Maiolo, V, additional, Sabatelli, L, additional, Ballarotto, M, additional, Salerno, R, additional, Napolano, A, additional, Giannelli, L, additional, Calovic, Z, additional, Vicedomini, G, additional, and Pappone, C, additional

Published
2024
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6. Alterations of the Sialylation Machinery in Brugada Syndrome

Author

Ghiroldi, A, Ciconte, G, Creo, P, Tarantino, A, Melgari, D, D'Imperio, S, Piccoli, M, Cirillo, F, Micaglio, E, Monasky, M, Frosio, A, Locati, E, Vicedomini, G, Rivolta, I, Pappone, C, Anastasia, L, Ghiroldi, A, Ciconte, G, Creo, P, Tarantino, A, Melgari, D, D'Imperio, S, Piccoli, M, Cirillo, F, Micaglio, E, Monasky, M, Frosio, A, Locati, E, Vicedomini, G, Rivolta, I, Pappone, C, and Anastasia, L

Abstract

Brugada Syndrome (BrS) is an inherited arrhythmogenic disorder with an increased risk of sudden cardiac death. Recent evidence suggests that BrS should be considered as an oligogenic or polygenic condition. Mutations in genes associated with BrS are found in about one-third of patients and they mainly disrupt the cardiac sodium channel NaV1.5, which is considered the main cause of the disease. However, voltage-gated channel’s activity could be impacted by post-translational modifications such as sialylation, but their role in BrS remains unknown. Thus, we analyzed high risk BrS patients (n = 42) and healthy controls (n = 42) to assess an involvement of sialylation in BrS. Significant alterations in gene expression and protein sialylation were detected in Peripheral Blood Mononuclear Cells (PBMCs) from BrS patients. These changes were significantly associated with the phenotypic expression of the disease, as the size of the arrhythmogenic substrate and the duration of epicardial electrical abnormalities. Moreover, protein desialylation caused a reduction in the sodium current in an in vitro NaV1.5-overexpressing model. Dysregulation of the sialylation machinery provides definitive evidence that BrS affects extracardiac tissues, suggesting an underlying cause of the disease. Moreover, detection of these changes at the systemic level and their correlation with the clinical phenotype hint at the existence of a biomarker signature for BrS.

Published
2022

7. Brugada syndrome genetics is associated with phenotype severity

Author

Ciconte, G, Monasky, M, Santinelli, V, Micaglio, E, Vicedomini, G, Anastasia, L, Negro, G, Borrelli, V, Giannelli, L, Santini, F, de Innocentiis, C, Rondine, R, Locati, E, Bernardini, A, Mazza, B, Mecarocci, V, Ćalović, Ž, Ghiroldi, A, D'Imperio, S, Benedetti, S, Di Resta, C, Rivolta, I, Casari, G, Petretto, E, Pappone, C, Ciconte, Giuseppe, Monasky, Michelle M, Santinelli, Vincenzo, Micaglio, Emanuele, Vicedomini, Gabriele, Anastasia, Luigi, Negro, Gabriele, Borrelli, Valeria, Giannelli, Luigi, Santini, Francesca, de Innocentiis, Carlo, Rondine, Roberto, Locati, Emanuela T, Bernardini, Andrea, Mazza, Beniamino C, Mecarocci, Valerio, Ćalović, Žarko, Ghiroldi, Andrea, D'Imperio, Sara, Benedetti, Sara, Di Resta, Chiara, Rivolta, Ilaria, Casari, Giorgio, Petretto, Enrico, Pappone, Carlo, Ciconte, G, Monasky, M, Santinelli, V, Micaglio, E, Vicedomini, G, Anastasia, L, Negro, G, Borrelli, V, Giannelli, L, Santini, F, de Innocentiis, C, Rondine, R, Locati, E, Bernardini, A, Mazza, B, Mecarocci, V, Ćalović, Ž, Ghiroldi, A, D'Imperio, S, Benedetti, S, Di Resta, C, Rivolta, I, Casari, G, Petretto, E, Pappone, C, Ciconte, Giuseppe, Monasky, Michelle M, Santinelli, Vincenzo, Micaglio, Emanuele, Vicedomini, Gabriele, Anastasia, Luigi, Negro, Gabriele, Borrelli, Valeria, Giannelli, Luigi, Santini, Francesca, de Innocentiis, Carlo, Rondine, Roberto, Locati, Emanuela T, Bernardini, Andrea, Mazza, Beniamino C, Mecarocci, Valerio, Ćalović, Žarko, Ghiroldi, Andrea, D'Imperio, Sara, Benedetti, Sara, Di Resta, Chiara, Rivolta, Ilaria, Casari, Giorgio, Petretto, Enrico, and Pappone, Carlo

Abstract

Aims : Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype-phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype-phenotype correlation in BrS. Methods and results: Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. Conclusion : In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

Published
2021

9. General Anesthesia Attenuates Brugada Syndrome Phenotype Expression: Clinical Implications From a Prospective Clinical Trial

Author

Ciconte G., Santinelli V., Brugada J., Vicedomini G., Conti M., Monasky M. M., Borrelli V., Castracane W., Aloisio T., Giannelli L., Di Dedda U., Pozzi P., Ranucci M., Pappone C., Ciconte, G., Santinelli, V., Brugada, J., Vicedomini, G., Conti, M., Monasky, M. M., Borrelli, V., Castracane, W., Aloisio, T., Giannelli, L., Di Dedda, U., Pozzi, P., Ranucci, M., and Pappone, C.

Subjects
Adult, Male, propofol, Anesthetics, General, Middle Aged, Anesthesia, General, general anesthesia, type 1 Brugada pattern, Electrocardiography, Prospective Studie, Sevoflurane, Phenotype, Brugada syndrome, Female, Human
Abstract

Objectives: This study investigates the electrocardiographic-electrophysiological effects of administration of anesthetic drugs for general anesthesia (GA) in patients with BrS at high risk of sudden cardiac death (SCD). Background: The safety of anesthetic agents in Brugada syndrome (BrS) is under debate. Methods: All consecutive patients with spontaneous type 1 BrS electrocardiographic (ECG) patterns undergoing epicardial ablation of the arrhythmogenic substrate (AS) under GA were enrolled. Anesthesia was induced with single bolus of propofol and maintained with sevofluorane. ECG measurements were collected before, immediately after, and 20 min after induction of GA. Three-dimensional maps during GA and after ajmaline indicated the epicardial AS before ablation. Results: Thirty-six patients with BrS (32 male, 88.9%; mean age 38.8 ± 12.0 years) with a spontaneous type 1 ECG pattern underwent GA. Induction was performed using propofol at mean dose of 1.6 to 2.6 mg/kg (2.1 ± 0.3 mg/kg). Twenty-eight (28 of 36, 77.8%) patients showed a reversion to a nondiagnostic pattern. ST-segment elevation (0.32 ± 0.01 mV vs. 0.19 ± 0.02 mV; p < 0.001) and J-wave amplitude (0.47 ± 0.02 mV vs. 0.31 ± 0.03 mV; p < 0.001) decreased after propofol. The AS area during GA, in the absence of BrS pattern, significantly enlarged after administration of ajmaline (3.6 ± 0.5 cm2 vs. 20.3 ± 0.8 cm2). No patient developed malignant arrhythmias during GA induction and maintenance. Conclusions: This study shows that GA using single-bolus propofol and volatile anesthetics is safe in high-risk patients with BrS, and it may exert a modulating effect by reducing the manifestation of type 1 BrS pattern and AS in the form of epicardial abnormal ECGs. (Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701)

Published
2018

10. Intermittent alternance of Brugada ECG patterns: Insights from a unique electrophysiological phenomenon

Author

Ciconte G., Conti M., Vicedomini G., Santinelli V., Brugada J., Pappone C., Ciconte, G., Conti, M., Vicedomini, G., Santinelli, V., Brugada, J., and Pappone, C.

Subjects
Adult, Time Factor, ECG, arrhythmic genetic syndrome, sudden death, Predictive Value of Test, intermittent Brugada pattern, Electrocardiography, Heart Conduction System, Heart Rate, Ablation Technique, Brugada syndrome, Action Potential, Human
Published
2017

11. Multipoint left ventricular pacing in a single coronary sinus branch improves mid-term echocardiographic and clinical response to cardiac resynchronization therapy

Author

Pappone C., Calovic Z., Vicedomini G., Cuko A., McSpadden L. C., Ryu K., Romano E., Baldi M., Saviano M., Pappone A., Ciaccio C., Giannelli L., Ionescu B., Petretta A., Vitale R., Fundaliotis A., Tavazzi L., Santinelli V., Pappone, C., Calovic, Z., Vicedomini, G., Cuko, A., Mcspadden, L. C., Ryu, K., Romano, E., Baldi, M., Saviano, M., Pappone, A., Ciaccio, C., Giannelli, L., Ionescu, B., Petretta, A., Vitale, R., Fundaliotis, A., Tavazzi, L., and Santinelli, V.

Subjects
Male, Pacemaker, Artificial, Time Factor, Cardiac Pacing, Artificial, multipoint pacing, cardiac resynchronization therapy, heart failure, LV modeling, Stroke Volume, Equipment Design, Recovery of Function, Middle Aged, pressure-volume loop, Ventricular Function, Left, Heart Ventricle, Cardiac Resynchronization Therapy Device, Treatment Outcome, Italy, CRT response, Coronary Sinu, Ventricular Pressure, Female, Human, Aged, Ultrasonography
Abstract

Multipoint LV Pacing Improves Mid-Term CRT Response Introduction Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing in a single coronary sinus branch improves acute LV function. We hypothesized that multipoint pacing (MPP) can improve midterm echocardiographic and clinical response compared with conventional CRT. Methods and Results Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical, Sylmar, CA, USA) were randomized to receive biventricular (BiV) pacing with either conventional LV pacing (CONV group) or MPP (MPP group). For each patient, an optimal pacing configuration for the assigned pacing mode was programmed based on intraoperative pressure-volume (PV) loop measurements. A clinical evaluation and transthoracic echocardiogram were performed before implant (BASELINE) and at 3 months postimplant and analyzed by a blinded observer. A reduction in end-systolic volume (ESV) of ≥15% relative to BASELINE was prospectively defined as response to CRT. Forty-four patients (NYHA Class III, EF 29 ± 6%, QRS duration 152 ± 17 milliseconds) were enrolled and randomized. One patient in the MPP group was lost to follow-up and excluded from further analysis. After 3 months, 11 of 22 (50%) CONV patients and 16 of 21 (76%) MPP patients were classified as responders. ESV reduction, EF increase, and NYHA class reduction relative to BASELINE were significantly greater in the MPP group than in the CONV group (ESV: -21.0 ± 13.9 vs. -12.6 ± 11.1%, P = 0.03; EF: +9.8 ± 5.1 vs. +2.0 ± 7.8 percentage points, P < 0.001; ΔNYHA: -1.05 ± 0.22 vs. -0.72 ± 0.46 functional classes, P = 0.006). Conclusion PV loop optimized BiV pacing with MPP resulted in an improved rate of response to CRT.

Published
2015

14. Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study

Author

Pappone C, Vicedomini G, Manguso F, Baldi M, Pappone A, Petretta A, Vitale R, Saviano M, Ciaccio C, Giannelli L, Calovic Z, Tavazzi L, Santinelli V, Pappone, C, Vicedomini, G, Manguso, F, Baldi, M, Pappone, A, Petretta, A, Vitale, R, Saviano, M, Ciaccio, C, Giannelli, L, Calovic, Z, Tavazzi, L, and Santinelli, V

Published
2012

15. An update on atrial fibrillation in 2014 : From pathophysiology to treatment

Author

Ferrari, R, Bertini, M, Blomström-Lundqvist, Carina, Dobrev, D, Kirchhof, P, Pappone, C, Ravens, U, Tamargo, J, Tavazzi, L, Vicedomini, G G, Ferrari, R, Bertini, M, Blomström-Lundqvist, Carina, Dobrev, D, Kirchhof, P, Pappone, C, Ravens, U, Tamargo, J, Tavazzi, L, and Vicedomini, G G

Abstract

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy.

Published
2016
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23. Long-term outcome of remote catheter ablation using a magnetic irrigated-tip catheter

Author

Santinelli V, Radinovic A, Vicedomini G, Ciconte G, Mazzone P, Augello G, Gulletta S, Sala S, Paglino G, M Saviano, Sacchi S, Vergara P, Pappone C, Santinelli, V, Radinovic, A, Vicedomini, G, Ciconte, G, Mazzone, P, Augello, G, Gulletta, S, Sala, S, Paglino, G, M, Saviano, Sacchi, S, Vergara, P, and Pappone, C

Published
2009

28. The natural history of ventricular preexcitation in 293 asymptomatic adult subjects

Author

Santinelli V, Radinovic A, Ciconte G, Vicedomini G, Mazzone P, Gulletta S, Paglino G, Sala S, Ciaccio C, Sacchi S, Avitabile M, Saviano M, Augello G, Santagostino A, Vergara P, Pappone C, Santinelli, V, Radinovic, A, Ciconte, G, Vicedomini, G, Mazzone, P, Gulletta, S, Paglino, G, Sala, S, Ciaccio, C, Sacchi, S, Avitabile, M, Saviano, M, Augello, G, Santagostino, A, Vergara, P, and Pappone, C

Published
2009

30. Atrial Fibrillation Progression in Patients With and Without Lone Atrial Fibrillation: A Five-Year Prospective Follow-Up Study

Author

Santinelli V, Radinovic A, Manguso F, Sala S, Vicedomini G, Mazzone P, Ciconte G, Frigoli E, Augello G, Gelera E, Gulletta S, Saviano M, Pappone A, Paglino G, Pappone C, Santinelli, V, Radinovic, A, Manguso, F, Sala, S, Vicedomini, G, Mazzone, P, Ciconte, G, Frigoli, E, Augello, G, Gelera, E, Gulletta, S, Saviano, M, Pappone, A, Paglino, G, and Pappone, C

Published
2008

31. Safety, Efficacy and Follow-Up of Circumferential Pulmonary Vein Ablation in Octogenarians

Author

Santinelli V, Radinovic A, Sala S, Vicedomini G, Mazzone P, Gulletta S, Ciaccio C, Ciconte G, Paglino G Augello G, Gelera E, Frigoli E, Santagostino A, Pappone C, Santinelli, V, Radinovic, A, Sala, S, Vicedomini, G, Mazzone, P, Gulletta, S, Ciaccio, C, Ciconte, G, Paglino, G Augello G, Gelera, E, Frigoli, E, Santagostino, A, and Pappone, C

Published
2008

37. AF ablation in the elderly population. The Milan experience

Author

Santinelli V, Radinovic A, Vicedomini G, Mazzone P, Gulletta S, Paglino G, Ciconte G, Augello G, Cuko A, Pappone C, Santinelli, V, Radinovic, A, Vicedomini, G, Mazzone, P, Gulletta, S, Paglino, G, Ciconte, G, Augello, G, Cuko, A, and Pappone, C

Published
2008

44. A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study

Author

Pappone C, Augello G, Sala S, Gugliotta F, Vicedomini G, Gulletta S, Paglino G, Mazzone P, Sora N, Greiss I, Santagostino A, LiVolsi L, Pappone N, Radinovic A, Manguso F, Santinelli V, Pappone, C, Augello, G, Sala, S, Gugliotta, F, Vicedomini, G, Gulletta, S, Paglino, G, Mazzone, P, Sora, N, Greiss, I, Santagostino, A, Livolsi, L, Pappone, N, Radinovic, A, Manguso, F, and Santinelli, V

Published
2006

45. Circumferential Pulmonary vein ablation versus antiarrhythmic drug therapy for paroxysmal atrial fibrillation. A long-term randomized trial (APAF Study)

Author

Pappone C, Augello G, Sala S, Radinovic A, Vicedomini G, Gugliotta F, Mazzone P, Santagostino A, Livolsi L, Marzi A, Frigoli E, Sacco F, Avitabile M, Pappone N, Stuto A, Santinelli V, Pappone, C, Augello, G, Sala, S, Radinovic, A, Vicedomini, G, Gugliotta, F, Mazzone, P, Santagostino, A, Livolsi, L, Marzi, A, Frigoli, E, Sacco, F, Avitabile, M, Pappone, N, Stuto, A, and Santinelli, V

Published
2006

46. Robotic magnetic navigation for atrial fibrillation ablation

Author

Pappone C, Vicedomini G, Manguso F, Gugliotta F, Mazzone P, Gulletta S, Sora N, Sala S, Marzi A, Augello G, Livolsi L, Santagostino A, Santinelli V, Pappone, C, Vicedomini, G, Manguso, F, Gugliotta, F, Mazzone, P, Gulletta, S, Sora, N, Sala, S, Marzi, A, Augello, G, Livolsi, L, Santagostino, A, and Santinelli, V

Published
2006

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