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1. Technology update: intracardiac echocardiography – a review of the literature

Author

Vitulano N, Pazzano V, Pelargonio G, and Narducci ML

Subjects
Medical technology, R855-855.5
Abstract

Nicola Vitulano, Vincenzo Pazzano, Gemma Pelargonio, Maria Lucia Narducci Institute of Cardiology, Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy Abstract: The development of new imaging tools helps in better investigation of cardiac structures and function by showing detailed images during interventional procedures. Intracardiac echocardiography plays a pivotal role as an intraoperative real-time imaging tool during invasive cardiac procedures. Initially, this echocardiographic technique was particularly useful when transthoracic image quality was insufficient and to avoid general anesthesia for transesophageal imaging. Nowadays, intracardiac echocardiography is routinely used in several cardiac invasive laboratories to support several types of procedures, such as extraction and implantation of cardiac devices, electrophysiological mapping, ablation, and endomyocardial biopsies. This review gives an overview of the basic principles of intracardiac echocardiography and examines its applications in the different settings of invasive cardiology. Keywords: ICE, cardiovascular imaging, electrophysiology, invasive cardiology

Published
2015

2. Intermuscular technique for implantation of the subcutaneous implantable defibrillator: a propensity-matched case-control study

Author

Botto, G, Ziacchi, M, Nigro, G, D'Onofrio, A, Dello Russo, A, Francia, P, Viani, S, Pisano, E, Bisignani, G, Caravati, F, Migliore, F, De Filippo, P, Ottaviano, L, Rordorf, R, Manzo, M, Canevese, F, Lovecchio, M, Valsecchi, S, Checchi, L, Casale, M, Schintu, B, Scalone, A, Tola, G, Setzu, A, Curcio, A, Santoro, A, Baiocchi, C, Gentilini, R, Lunghetti, S, Solimene, F, Shopova, G, Schillaci, V, Arestia, A, Agresta, A, Bianchi, S, Rossi, P, Cauti, F, La Greca, C, Pecora, D, Ammirati, F, Santini, L, Mahfouz, K, Colaiaco, C, Vicentini, A, Savastano, S, Petracci, B, Sanzo, A, Baldi, E, Casula, M, Perego, G, Rella, V, Bianchi, V, Tavoletta, V, De Vivo, S, Palmisano, P, Accogli, M, Milanese, G, Pepi, P, Nicolis, D, Mariani, M, Pagani, M, Bonfantino, M, Caccavo, V, Grimaldi, M, Katsouras, G, Forleo, G, Chieffo, E, Tavarelli, E, Brambilla, R, Pani, A, Giammaria, M, Lucciola, M, Amellone, C, Uran, C, Baroni, M, Ferrari, P, Leidi, C, Drago, F, Silvetti, M, Pazzano, V, Russo, S, Remoli, R, Battipaglia, I, Cazzoli, I, Saputo, F, Devecchi, C, Barbonaglia, L, Viscusi, M, Brignoli, M, Mattera, A, Pedretti, S, Lupi, A, Tommasi, S, Kol, A, Gatto, M, Persi, A, Gonella, A, Rossetti, G, Menardi, E, Rossini, R, Notarstefano, P, Nesti, M, Fraticelli, A, Carreras, G, Donzelli, S, Marini, C, Tordini, A, Lazzari, L, Sartori, P, Di Donna, P, Mascia, G, Capogrosso, P, Magliano, P, Colimodio, M, Sala, S, Mazzone, P, Della Bella, P, Coppolino, A, Arena, G, Borrello, V, Ratti, M, Bartoli, C, Palano, F, Adduci, C, Torriglia, A, Laffi, M, Esposito, C, Giano, A, Franculli, F, Pangallo, A, De Bonis, S, Sarubbi, B, Colonna, D, Correra, A, Romeo, E, Rapacciuolo, A, Liguori, V, Viggiano, A, Strisciullo, T, Biffi, M, Diemberger, I, Martignani, C, Piro, A, Lavalle, C, Magnocavallo, M, Ricciardi, D, Calabrese, V, Gioia, F, Picarelli, F, Licciardello, G, Busacca, G, Calvi, V, Lamberti, F, Lumia, G, Bellini, C, Bianchi, C, Savarese, G, Andreoli, C, Pimpinicchio, L, Pellegrini, D, Giorgi, D, Bovenzi, Busoni, F, Daleffe, E, Facchin, D, Rebellato, L, Stifano, G, Magliano, G, Sergi, D, Barone, L, Morgagni, R, Casella, M, Guerra, F, Cipolletta, L, Molini, S, De Lucia, R, Di Cori, A, Grifoni, G, Paperini, L, Segreti, L, Soldati, E, Zucchelli, G, Russo, V, Rago, A, Ammendola, E, Papa, A, Pieragnoli, P, Ricciardi, G, Perrotta, L, Botto G. L., Ziacchi M., Nigro G., D'Onofrio A., Dello Russo A., Francia P., Viani S., Pisano E., Bisignani G., Caravati F., Migliore F., De Filippo P., Ottaviano L., Rordorf R., Manzo M., Canevese F. L., Lovecchio M., Valsecchi S., Checchi L., Casale M. C., Schintu B., Scalone A., Tola G., Setzu A., Curcio A., Santoro A., Baiocchi C., Gentilini R., Lunghetti S., Solimene F., Shopova G., Schillaci V., Arestia A., Agresta A., Bianchi S., Rossi P., Cauti F. M., La Greca C., Pecora D., Ammirati F., Santini L., Mahfouz K., Colaiaco C., Vicentini A., Savastano S., Petracci B., Sanzo A., Baldi E., Casula M., Perego G. B., Rella V., Bianchi V., Tavoletta V., De Vivo S., Palmisano P., Accogli M., Milanese G., Pepi P., Nicolis D., Mariani M., Pagani M., Bonfantino M. V., Caccavo V., Grimaldi M., Katsouras G., Forleo G. B., Chieffo E., Tavarelli E., Brambilla R., Pani A., Giammaria M., Lucciola M. T., Amellone C., Uran C., Baroni M., Ferrari P., Leidi C., Drago F., Silvetti M. S., Pazzano V., Russo S., Remoli R., Battipaglia I., Cazzoli I., Saputo F., Devecchi C., Barbonaglia L., Viscusi M., Brignoli M., Mattera A., Pedretti S., Lupi A., Tommasi S., Kol A., Gatto M. C., Persi A., Gonella A., Rossetti G., Menardi E., Rossini R., Notarstefano P., Nesti M., Fraticelli A., Carreras G., Donzelli S., Marini C., Tordini A., Lazzari L., Sartori P., Di Donna P., Mascia G., Capogrosso P., Magliano P., Colimodio M., Sala S., Mazzone P., Della Bella P., Coppolino A., Arena G., Borrello V., Ratti M., Bartoli C., Palano F., Adduci C., Torriglia A., Laffi M., Esposito C., Giano A., Franculli F., Pangallo A., De Bonis S., Sarubbi B., Colonna D., Correra A., Romeo E., Rapacciuolo A., Liguori V., Viggiano A., Strisciullo T., Biffi M., Diemberger I., Martignani C., Piro A., Lavalle C., Magnocavallo M., Mariani M. V., Ricciardi D., Calabrese V., Gioia F., Picarelli F., Licciardello G., Busacca G., Calvi V. I., Lamberti F., Lumia G., Bellini C., Bianchi C., Savarese G., Andreoli C., Pimpinicchio L., Pellegrini D., Giorgi D., Busoni F., Daleffe E., Facchin D., Rebellato L., Stifano G., Magliano G., Sergi D., Barone L., Morgagni R., Casella M., Guerra F., Cipolletta L., Molini S., De Lucia R., Di Cori A., Grifoni G., Paperini L., Segreti L., Soldati E., Zucchelli G., Russo V., Rago A., Ammendola E., Papa A., Pieragnoli P., Ricciardi G., Perrotta L., Botto, G, Ziacchi, M, Nigro, G, D'Onofrio, A, Dello Russo, A, Francia, P, Viani, S, Pisano, E, Bisignani, G, Caravati, F, Migliore, F, De Filippo, P, Ottaviano, L, Rordorf, R, Manzo, M, Canevese, F, Lovecchio, M, Valsecchi, S, Checchi, L, Casale, M, Schintu, B, Scalone, A, Tola, G, Setzu, A, Curcio, A, Santoro, A, Baiocchi, C, Gentilini, R, Lunghetti, S, Solimene, F, Shopova, G, Schillaci, V, Arestia, A, Agresta, A, Bianchi, S, Rossi, P, Cauti, F, La Greca, C, Pecora, D, Ammirati, F, Santini, L, Mahfouz, K, Colaiaco, C, Vicentini, A, Savastano, S, Petracci, B, Sanzo, A, Baldi, E, Casula, M, Perego, G, Rella, V, Bianchi, V, Tavoletta, V, De Vivo, S, Palmisano, P, Accogli, M, Milanese, G, Pepi, P, Nicolis, D, Mariani, M, Pagani, M, Bonfantino, M, Caccavo, V, Grimaldi, M, Katsouras, G, Forleo, G, Chieffo, E, Tavarelli, E, Brambilla, R, Pani, A, Giammaria, M, Lucciola, M, Amellone, C, Uran, C, Baroni, M, Ferrari, P, Leidi, C, Drago, F, Silvetti, M, Pazzano, V, Russo, S, Remoli, R, Battipaglia, I, Cazzoli, I, Saputo, F, Devecchi, C, Barbonaglia, L, Viscusi, M, Brignoli, M, Mattera, A, Pedretti, S, Lupi, A, Tommasi, S, Kol, A, Gatto, M, Persi, A, Gonella, A, Rossetti, G, Menardi, E, Rossini, R, Notarstefano, P, Nesti, M, Fraticelli, A, Carreras, G, Donzelli, S, Marini, C, Tordini, A, Lazzari, L, Sartori, P, Di Donna, P, Mascia, G, Capogrosso, P, Magliano, P, Colimodio, M, Sala, S, Mazzone, P, Della Bella, P, Coppolino, A, Arena, G, Borrello, V, Ratti, M, Bartoli, C, Palano, F, Adduci, C, Torriglia, A, Laffi, M, Esposito, C, Giano, A, Franculli, F, Pangallo, A, De Bonis, S, Sarubbi, B, Colonna, D, Correra, A, Romeo, E, Rapacciuolo, A, Liguori, V, Viggiano, A, Strisciullo, T, Biffi, M, Diemberger, I, Martignani, C, Piro, A, Lavalle, C, Magnocavallo, M, Ricciardi, D, Calabrese, V, Gioia, F, Picarelli, F, Licciardello, G, Busacca, G, Calvi, V, Lamberti, F, Lumia, G, Bellini, C, Bianchi, C, Savarese, G, Andreoli, C, Pimpinicchio, L, Pellegrini, D, Giorgi, D, Bovenzi, Busoni, F, Daleffe, E, Facchin, D, Rebellato, L, Stifano, G, Magliano, G, Sergi, D, Barone, L, Morgagni, R, Casella, M, Guerra, F, Cipolletta, L, Molini, S, De Lucia, R, Di Cori, A, Grifoni, G, Paperini, L, Segreti, L, Soldati, E, Zucchelli, G, Russo, V, Rago, A, Ammendola, E, Papa, A, Pieragnoli, P, Ricciardi, G, Perrotta, L, Botto G. L., Ziacchi M., Nigro G., D'Onofrio A., Dello Russo A., Francia P., Viani S., Pisano E., Bisignani G., Caravati F., Migliore F., De Filippo P., Ottaviano L., Rordorf R., Manzo M., Canevese F. L., Lovecchio M., Valsecchi S., Checchi L., Casale M. C., Schintu B., Scalone A., Tola G., Setzu A., Curcio A., Santoro A., Baiocchi C., Gentilini R., Lunghetti S., Solimene F., Shopova G., Schillaci V., Arestia A., Agresta A., Bianchi S., Rossi P., Cauti F. M., La Greca C., Pecora D., Ammirati F., Santini L., Mahfouz K., Colaiaco C., Vicentini A., Savastano S., Petracci B., Sanzo A., Baldi E., Casula M., Perego G. B., Rella V., Bianchi V., Tavoletta V., De Vivo S., Palmisano P., Accogli M., Milanese G., Pepi P., Nicolis D., Mariani M., Pagani M., Bonfantino M. V., Caccavo V., Grimaldi M., Katsouras G., Forleo G. B., Chieffo E., Tavarelli E., Brambilla R., Pani A., Giammaria M., Lucciola M. T., Amellone C., Uran C., Baroni M., Ferrari P., Leidi C., Drago F., Silvetti M. S., Pazzano V., Russo S., Remoli R., Battipaglia I., Cazzoli I., Saputo F., Devecchi C., Barbonaglia L., Viscusi M., Brignoli M., Mattera A., Pedretti S., Lupi A., Tommasi S., Kol A., Gatto M. C., Persi A., Gonella A., Rossetti G., Menardi E., Rossini R., Notarstefano P., Nesti M., Fraticelli A., Carreras G., Donzelli S., Marini C., Tordini A., Lazzari L., Sartori P., Di Donna P., Mascia G., Capogrosso P., Magliano P., Colimodio M., Sala S., Mazzone P., Della Bella P., Coppolino A., Arena G., Borrello V., Ratti M., Bartoli C., Palano F., Adduci C., Torriglia A., Laffi M., Esposito C., Giano A., Franculli F., Pangallo A., De Bonis S., Sarubbi B., Colonna D., Correra A., Romeo E., Rapacciuolo A., Liguori V., Viggiano A., Strisciullo T., Biffi M., Diemberger I., Martignani C., Piro A., Lavalle C., Magnocavallo M., Mariani M. V., Ricciardi D., Calabrese V., Gioia F., Picarelli F., Licciardello G., Busacca G., Calvi V. I., Lamberti F., Lumia G., Bellini C., Bianchi C., Savarese G., Andreoli C., Pimpinicchio L., Pellegrini D., Giorgi D., Busoni F., Daleffe E., Facchin D., Rebellato L., Stifano G., Magliano G., Sergi D., Barone L., Morgagni R., Casella M., Guerra F., Cipolletta L., Molini S., De Lucia R., Di Cori A., Grifoni G., Paperini L., Segreti L., Soldati E., Zucchelli G., Russo V., Rago A., Ammendola E., Papa A., Pieragnoli P., Ricciardi G., and Perrotta L.

Abstract

Aims A previous randomized study demonstrated that the subcutaneous implantable cardioverter defibrillator (S-ICD) was noninferior to transvenous ICD with respect to device-related complications and inappropriate shocks. However, that was performed prior to the widespread adoption of pulse generator implantation in the intermuscular (IM) space instead of the traditional subcutaneous (SC) pocket. The aim of this analysis was to compare survival from device-related complications and inappropriate shocks between patients who underwent S-ICD implantation with the generator positioned in an IM position in comparison with an SC pocket. Methods and results We analysed 1577 consecutive patients who had undergone S-ICD implantation from 2013 to 2021 and were followed up until December 2021. Subcutaneous patients (n = 290) were propensity matched with patients of the IM group (n = 290), and their outcomes were compared. : During a median follow-up of 28 months, device-related complications were reported in 28 (4.8%) patients and inappropriate shocks were reported in 37 (6.4%) patients. The risk of complication was lower in the matched IM group than in the SC group [hazard ratio 0.41, 95% confidence interval (CI) 0.17-0.99, P = 0.041], as well as the composite of complications and inappropriate shocks (hazard ratio 0.50, 95% CI 0.30-0.86, P = 0.013). The risk of appropriate shocks was similar between groups (hazard ratio 0.90, 95% CI 0.50-1.61, P = 0.721). There was no significant interaction between generator positioning and variables such as gender, age, body mass index, and ejection fraction. Conclusion Our data showed the superiority of the IM S-ICD generator positioning in reducing device-related complications and inappropriate shocks.

Published
2023

4. Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients

Author

Pedicino, Daniela, Severino, Anna, Di Sante, Gabriele, De Rosa, Maria Cristina, Pirolli, Davide, Vinci, Ramona, Pazzano, V., Giglio, A. F., Trotta, F., Russo, G., Ruggio, A., Pisano, Eugenia, D'Aiello, Alessia, Canonico, Francesco, Ciampi, P., Cianflone, D., Cianfanelli, L., Grimaldi, Maria Chiara, Filomia, Simone, Luciani, Nicola, Glieca, Franco, Bruno, Piergiorgio, Massetti, Massimo, Ria, Francesco, Crea, Filippo, Liuzzo, Giovanna, Pedicino D., Severino A., Di Sante G. (ORCID:0000-0001-6608-3388), De Rosa M. C., Pirolli D. (ORCID:0000-0003-2303-2577), Vinci R., Pisano E., d'Aiello A., Canonico F. (ORCID:0000-0001-6936-4548), Grimaldi M. C., Filomia S., Luciani N. (ORCID:0000-0002-9407-0303), Glieca F. (ORCID:0000-0003-3645-7152), Bruno P. (ORCID:0000-0002-1075-5808), Massetti M. (ORCID:0000-0002-7100-8478), Ria F. (ORCID:0000-0002-8444-0307), Crea F. (ORCID:0000-0001-9404-8846), Liuzzo G. (ORCID:0000-0002-5714-0907), Pedicino, Daniela, Severino, Anna, Di Sante, Gabriele, De Rosa, Maria Cristina, Pirolli, Davide, Vinci, Ramona, Pazzano, V., Giglio, A. F., Trotta, F., Russo, G., Ruggio, A., Pisano, Eugenia, D'Aiello, Alessia, Canonico, Francesco, Ciampi, P., Cianflone, D., Cianfanelli, L., Grimaldi, Maria Chiara, Filomia, Simone, Luciani, Nicola, Glieca, Franco, Bruno, Piergiorgio, Massetti, Massimo, Ria, Francesco, Crea, Filippo, Liuzzo, Giovanna, Pedicino D., Severino A., Di Sante G. (ORCID:0000-0001-6608-3388), De Rosa M. C., Pirolli D. (ORCID:0000-0003-2303-2577), Vinci R., Pisano E., d'Aiello A., Canonico F. (ORCID:0000-0001-6936-4548), Grimaldi M. C., Filomia S., Luciani N. (ORCID:0000-0002-9407-0303), Glieca F. (ORCID:0000-0003-3645-7152), Bruno P. (ORCID:0000-0002-1075-5808), Massetti M. (ORCID:0000-0002-7100-8478), Ria F. (ORCID:0000-0002-8444-0307), Crea F. (ORCID:0000-0001-9404-8846), and Liuzzo G. (ORCID:0000-0002-5714-0907)

Abstract

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent wit

Published
2022

10. Role of Right Ventricular Three-Dimensional Electroanatomic Voltage Mapping for the Arrhythmic Risk Stratification of Patients with Corrected Tetralogy of Fallot or Other Congenital Heart Disease Involving the Right Ventricle Outflow Tract

Author

Pazzano, V., primary, Di Mambro, C., additional, Russo, M., additional, Silvetti, M., additional, Palmieri, R., additional, Fabrizio, Gimigliano, additional, Giannico, S., additional, Leonardi, B., additional, Amodeo, A., additional, Di Ciommo, V., additional, and Drago, F., additional

Published
2016
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11. Role of tissue C-reactive protein in atrial cardiomyocytes of patients undergoing catheter ablation of atrial fibrillation: pathogenetic implications

Author

Narducci, M. L., primary, Pelargonio, G., additional, Dello Russo, A., additional, Casella, M., additional, Biasucci, L. M., additional, La Torre, G., additional, Pazzano, V., additional, Santangeli, P., additional, Baldi, A., additional, Liuzzo, G., additional, Tondo, C., additional, Natale, A., additional, and Crea, F., additional

Published
2011
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13. Role of tissue C-reactive protein in atrial cardiomyocytes of patients undergoing catheter ablation of atrial fibrillation: pathogenetic implications

Author

Michela Casella, Vincenzo Pazzano, Maria Lucia Narducci, Andrea Natale, Filippo Crea, Alfonso Baldi, Giuseppe La Torre, Gemma Pelargonio, Pasquale Santangeli, Antonio Russo, Luigi M. Biasucci, Claudio Tondo, Giovanna Liuzzo, Narducci, Ml, Pelargonio, G, DELLO RUSSO, A, Casella, M, Biasucci, Lm, LA TORRE, G, Pazzano, V, Santangeli, P, Baldi, Alfonso, Liuzzo, G, Tondo, C, Natale, A, and Crea, F.

Subjects
Male, medicine.medical_specialty, Cytoplasm, medicine.medical_treatment, Biopsy, Catheter ablation, Inflammation, Physiology (medical), Internal medicine, Atrial Fibrillation, medicine, Atrial endomyocardial biopsy, Humans, Myocytes, Cardiac, cardiovascular diseases, Heart Atria, Prospective Studies, Saline, Aged, medicine.diagnostic_test, biology, business.industry, C-reactive protein, Atrial fibrillation, Middle Aged, medicine.disease, Myocarditis, C-Reactive Protein, c-reactive protein, atrial fibrillation, trans-septal puncture, atrial endomyocardial biopsy, Dilator, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Cardiology, biology.protein, Trans-septal puncture, Catheter Ablation, Immunohistochemistry, Feasibility Studies, Female, Wolff-Parkinson-White Syndrome, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
Abstract

Aims: Histological studies support the important role of inflammation in the initiation and maintenance of atrial fibrillation (AF). We describe a novel and safe technique of atrial biopsy during AF radiofrequency catheter ablation (RFCA) to investigate the role of atrial tissue inflammation. Methods and results: We enrolled 70 consecutive patients (age 60 ± 12 years, 49 males) undergoing RFCA for AF. The control group was represented by 10 patients with WolffParkinsonWhite syndrome undergoing trans-septal puncture. Atrial biopsies were obtained by washing the dilator and needle used for trans-septal puncture with 20 mL sterile phosphate-buffered saline. The presence of intracytoplasmic C-reactive protein was assessed in formalin-fixed atrial specimens by immunohistochemistry. A sufficient amount of atrial tissue was obtained in 23/70 (32) patients with AF and in 4/10 (40) of the control group. Intracytoplasmic localization of C-reactive protein was found in isolated atrial cardiomyocytes in 11 (73) of 15 patients with paroxysmal AF as compared with 2 (25) of eight patients with persistent AF (P 0.02). Conclusions: In this study, we demonstrate the safety and feasibility of a novel technique to obtain atrial specimens during routine trans-septal puncture. Local inflammation assessed by atrial tissue localization of C-reactive protein is more likely involved in paroxysmal rather than in persistent AF. © 2011 The Author.

Published
2011

14. Intermittent ventricular preexcitation in children: not always a low-risk condition.

Author

Yammine ML, Tamborrino PP, Flore F, Di Mambro C, Pazzano V, Di Marzio S, and Drago F

Subjects
Humans, Child, Male, Wolff-Parkinson-White Syndrome physiopathology, Wolff-Parkinson-White Syndrome diagnosis, Pre-Excitation Syndromes diagnosis, Pre-Excitation Syndromes physiopathology, Risk Factors, Female, Catheter Ablation, Electrocardiography
Abstract

Competing Interests: Conflict of interest: None declared.

Published
2024
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15. Transvenous lead advancement in pediatric pacing to overcome growth-induced lead straightening and stretching.

Author

Silvetti MS, Porco L, Campisi M, Pazzano V, Tamburri I, Saputo FA, Silvetti G, Ravà L, and Drago F

Subjects
Humans, Male, Female, Retrospective Studies, Child, Child, Preschool, Electrodes, Implanted, Atrioventricular Block therapy, Sick Sinus Syndrome therapy, Pacemaker, Artificial
Abstract

Background: The stretching of the lead caused by somatic growth may lead to complications (dislodgement, fracture, failure) of transvenous leads implanted in pediatric patients. Atrial loop and absorbable ligatures may prevent it. Periodical lead advancement with lead pushing from the pocket may be an option to growth-induced stretching. Our aim was to analyze retrospectively the outcome of periodical transvenous lead advancement in children with pacemaker (PM)., Methods: A procedure of lead advancement was performed in patients with a single-chamber PM implanted for isolated congenital complete atrioventricular block or sinus node dysfunction with growth-induced lead straightening/stretching. The PM pocket was opened, the lead was released from subcutaneous adherences and was gently advanced to shape again a loop/semi-loop in the atrium without dislodging the tip. Lead data (threshold, sensing, impedance) were compared before and after the procedure. Data are described as median (25th-75th centiles)., Results: 14 patients with 13 VVIR and 1 AAIR PM implanted at 6.8 (5.9-8.0) years of age, 23 (19-26) kg, 118 (108-124) cm, underwent 30 advancement procedures, 1.5 (1.0-2.3) per patient, during follow-up [45 (35-63) months]. Delta between procedures was: 18 (14-25) months, 11 (7-13) cm, 6 (4-9) kg; 90% of leads were successfully advanced without complications. Three unsuccessful procedures occurred with longer times [30 (14-37) months]. Electrical lead parameters did not show significant differences pre-/post-procedures., Conclusion: the advancement of transvenous leads in children seems safe and effective. This procedure may be another possible choice to preserve transvenous lead position and function until growth has completed., (© 2024 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Published
2024
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16. 3D transvenous radiofrequency ablation of manifest epicardial posterior-septal accessory pathways in children: Can technology innovations improve the outcome?

Author

Drago F, Tamborrino PP, Pazzano V, Di Mambro C, and Silvetti MS

Subjects
Adolescent, Child, Humans, Technology, Accessory Atrioventricular Bundle, Catheter Ablation methods, Coronary Sinus
Abstract

Introduction: The aim of the study was to revise our more recent experience about epicardial posterior-septal accessory pathways radiofrequency transcatheter ablation in children and young patients using a transvenous approach through the coronary sinus, to understand if new mapping and ablation technologies can increase success rate and safety., Methods and Results: Twenty children (mean age 13 ± 3 years) with epicardial posterior-septal accessory pathways (14 in coronary sinus and 6 in the middle cardiac vein) underwent radiofrequency transcatheter ablation with CARTO-3® system with help of the CARTO-Univu® module. Acute success rate was 73%. No patient was lost to follow-up (mean time 11.4 ± 9 months). The recurrence rate was 19%. Two patients underwent a successful redo-procedure; the overall long-term success rate was 65%. Navistar® catheter presented the highest acute success rate in the coronary sinus. Navistar SmartTouch® was the only catheter that did not present recurrences after the acute success, and it was successfully used in two patients previously unsuccessfully treated with a Navistar ThermoCool®. Acute success rate was 79% without image integration with angio-CT, while it was 63% after the introduction of CARTO-Merge®., Conclusion: Epicardial posterior-septal accessory pathways can be definitively eliminated by transvenous radiofrequency transcatheter ablation in more than half of the cases in children. Acute success rate does not seem to depend on catheters used, but contact-force catheter seems to be useful in cases with recurrences. Image integration with cardiac-CT does not increase success rate, but it is useful to detect coronary sinus alterations to better guide ablation strategy.

Published
2022
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17. Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients.

Author

Pedicino D, Severino A, Di Sante G, De Rosa MC, Pirolli D, Vinci R, Pazzano V, Giglio AF, Trotta F, Russo G, Ruggio A, Pisano E, d'Aiello A, Canonico F, Ciampi P, Cianflone D, Cianfanelli L, Grimaldi MC, Filomia S, Luciani N, Glieca F, Bruno P, Massetti M, Ria F, Crea F, and Liuzzo G

Subjects
Adipose Tissue, Epitopes, HLA-A3 Antigen, Humans, Leukocytes, Mononuclear, Proteome, T-Lymphocytes, Acute Coronary Syndrome, Non-ST Elevated Myocardial Infarction
Abstract

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression., Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS ( P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences., Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pedicino, Severino, Di Sante, De Rosa, Pirolli, Vinci, Pazzano, Giglio, Trotta, Russo, Ruggio, Pisano, d’Aiello, Canonico, Ciampi, Cianflone, Cianfanelli, Grimaldi, Filomia, Luciani, Glieca, Bruno, Massetti, Ria, Crea and Liuzzo.)

Published
2022
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18. Three-dimensional guided selective right ventricular septal pacing preserves ventricular systolic function and synchrony in pediatric patients.

Author

Silvetti MS, Pazzano V, Battipaglia I, Saputo FA, Mizzon C, Gimigliano F, Ammirati A, Ravà L, and Drago F

Subjects
Adolescent, Atrioventricular Block physiopathology, Atrioventricular Block therapy, Child, Echocardiography, Female, Follow-Up Studies, Heart Ventricles physiopathology, Humans, Male, Prospective Studies, Systole, Treatment Outcome, Ventricular Function, Left, Ventricular Septum, Atrioventricular Block diagnosis, Cardiac Pacing, Artificial methods, Heart Ventricles diagnostic imaging, Imaging, Three-Dimensional, Pacemaker, Artificial, Stroke Volume physiology
Abstract

Background: Nonfluoroscopic 3-dimensional (3D) electroanatomic mapping systems (EAMs) have been developed to guide cardiac catheter navigation and reduce fluoroscopy. Selective right ventricular (RV) septal pacing could prevent pacing-induced left ventricular (LV) dysfunction., Objective: The purpose of this study was to determine whether EAM-guided selective RV septal pacing preserves LV contractility/synchrony in pediatric patients with complete atrioventricular block (CAVB) and no other congenital heart defects., Methods: Prospective analysis of children/adolescents who underwent EAM-guided selective RV pacing was performed. A 3D pacing map guided ventricular lead implantation at septal sites with narrow paced QRS. Serial echocardiograms were obtained after pacemaker implantation to monitor for function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index). Data are reported as median (25th-75th percentile)., Results: Thirty-two CAVB patients (age 9.8 [7.0-14.0] years; 11 with a previous pacing system) underwent selective RV septal pacing (13 DDD, 19 VVIR pacemaker; midseptum 22, parahisian 7, RV outflow tract 3) with narrow paced QRS (110 [100-120] ms) and low radiation exposure. Follow-up over 24 (5-33) months showed preserved LV function and synchrony, without significant differences between pacing sites (midseptum-parahisian) and mode (VVIR-DDD). EF decreased after implantation in patients without previous pacing, although values were mainly within normal limits. Three parahisian patients underwent early lead repositioning., Conclusion: EAM-guided selective RV septal pacing is a feasible technique associated with preserved LV systolic function and synchrony and low radiation exposure in pediatric patients with CAVB., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Published
2021
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19. Low-voltage bridge strategy to guide cryoablation of typical and atypical atrioventricular nodal re-entry tachycardia in children: mid-term outcomes in a large cohort of patients.

Author

Drago F, Calvieri C, Russo MS, Remoli R, Pazzano V, Battipaglia I, Gimigliano F, Allegretti G, and Silvetti MS

Subjects
Adolescent, Child, Cohort Studies, Female, Humans, Male, Recurrence, Treatment Outcome, Catheter Ablation, Cryosurgery adverse effects, Tachycardia, Atrioventricular Nodal Reentry diagnosis, Tachycardia, Atrioventricular Nodal Reentry surgery
Abstract

Aims: In the current literature, results of the low-voltage bridge (LVB) ablation strategy for the definitive treatment of atrioventricular nodal re-entry tachycardia (AVNRT) seem to be encouraging also in children. The aims of this study were (i) to prospectively evaluate the mid-term efficacy of LVB ablation in a very large cohort of children with AVNRT, and (ii) to identify electrophysiological factors associated with recurrence., Methods and Results: One hundred and eighty-four children (42% male, mean age 13 ± 4 years) with AVNRT underwent transcatheter cryoablation guided by voltage mapping of the Koch's triangle. Acute procedural success was 99.2% in children showing AVNRT inducibility at the electrophysiological study. The overall recurrence rate was 2.7%. The presence of two LVBs, a longer fluoroscopy time and the presence of both typical and atypical AVNRT, were found to be significantly associated with an increased recurrence rate during mid-term follow-up. Conversely, there was no significant association between recurrences and patient's age, type of LVB, lesion length, number of cryolesions or catheter tip size., Conclusion: The LVB ablation strategy is very effective in AVNRT treatment in children. Recurrences are related to the complexity of the arrhythmogenic substrate., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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20. Subcutaneous implantable cardioverter-defibrillator: is it ready for use in children and young adults? A single-centre study.

Author

Silvetti MS, Pazzano V, Verticelli L, Battipaglia I, Saputo FA, Albanese S, Lovecchio M, Valsecchi S, and Drago F

Subjects
Adolescent, Adult, Age Factors, Body Mass Index, Child, Clinical Decision-Making, Death, Sudden, Cardiac etiology, Electric Countershock adverse effects, Female, Humans, Male, Patient Selection, Prosthesis Design, Prosthesis Failure, Registries, Retrospective Studies, Risk Assessment, Risk Factors, Rome, Time Factors, Treatment Outcome, Young Adult, Death, Sudden, Cardiac prevention & control, Defibrillators, Implantable adverse effects, Electric Countershock instrumentation
Abstract

Aims: Use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) to prevent sudden cardiac death is increasing. Few data exist on S-ICD in young patients. We reviewed our single-centre experience in order to assess the effectiveness and safety of S-ICD implantation, and to identify potential factors associated with complications., Methods and Results: Observational, non-randomized, standard-of-care study on S-ICD implantation/follow-up in young patients with inherited arrhythmias (IA), cardiomyopathies, and congenital heart defects (CHD). Fifteen patients (6 CHD, 8 cardiomyopathies, and 1 IA), median age 15 years (25th-75th centiles, 14-28), 10 of them <18 years, with body mass index (BMI) 22.6 ± 3.4, underwent S-ICD implantation (primary prevention 93%). The first six patients underwent a standard implantation procedure (three surgical incisions), the following nine a two-incision procedure. No intraoperative complications occurred. Over 12 (7-24) months follow-up, two patients received appropriate shocks and one (7%) inappropriate shock. Four patients had device-related complications requiring surgical intervention: three skin erosions at the superior parasternal incision, one pocket infection. A higher risk of complications was seen in patients who underwent standard procedures [hazard ratio (HR) 4.98, 95% confidence interval (CI) 1.53-47.36; P = 0.0482] and those with BMI <20 (HR 9.44, 95% CI 0.95-93.23; P = 0.0169)., Conclusion: S-ICD implantation was safe and effective in young patients with low rates of inappropriate shock. However, the risk of device-related complications during follow-up remains substantial in patients with low BMI. To prevent possible complications, a two-incision technique should be preferred.

Published
2018
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21. Electroanatomic mapping-guided localization of alternative right ventricular septal pacing sites in children.

Author

Silvetti MS, Battipaglia I, Pazzano V, Saputo FA, Ravà L, Ammirati A, Calvieri C, Ciani M, and Drago F

Subjects
Child, Child, Preschool, Female, Fluoroscopy, Humans, Male, Prospective Studies, Treatment Outcome, Atrioventricular Block physiopathology, Atrioventricular Block therapy, Cardiac Pacing, Artificial methods, Heart Ventricles physiopathology, Pacemaker, Artificial, Ventricular Dysfunction, Left physiopathology, Ventricular Dysfunction, Left prevention & control
Abstract

Background: Alternative right ventricular (RV) sites (RVAPS) have been proposed to prevent or reduce RV pacing-induced left-ventricular (LV) dysfunction. Nonfluoroscopic 3D electroanatomic mapping systems (EAM) have been developed to guide cardiac catheter navigation and reduce fluoroscopy during electrophysiological procedures or pacemaker implantations., Aim: The aim of the study was to compare the results of EAM-guided permanent pacemaker implantation aiming at RVAPS with conventional fluoroscopic-guided implantation in RV apex (RVA) in children and adolescents., Methods: A prospective, randomized analysis was performed on children/adolescents with complete atrioventricular block (CAVB) who underwent EAM-guided pacemaker and transvenous leads implantation into RVAPS (EAM-RVAPS) or conventional, fluoroscopic-guided implantation into RV apex (RVA). In EAM-RVAPS, a pacing map guided the implantation of ventricular leads in septal sites with narrower QRS. After implantation, LV contractility (ejection fraction [EF], Global Longitudinal Strain [GLS]) and synchrony were evaluated at 1-12 months., Results: Twenty-one pediatric patients with CAVB, with (six patients) or without structural heart diseases, aged 4-16 (median 10.5) years, were divided in two groups: EAM-RVAPS (11 patients, four dual-chamber/DDD, seven single-chamber/VVIR pacemakers) and RVA (10 patients, one DDD/nine VVIR). The two groups did not show significant differences for preoperative parameters. EAM-RVAPS showed: preserved LVEF and synchrony (not significantly different than RVA), significantly lower GLS and radiation doses/exposures, in spite more complex procedures, significantly longer procedure times and narrower paced QRS than RVA., Conclusions: EAM-guided procedures have been useful to reduce radiation exposure and to localize RVAPS with narrower paced QRS and lower GLS than RVA., (© 2018 Wiley Periodicals, Inc.)

Published
2018
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22. Physiological pacing in young patients with complex congenital heart defects.

Author

Silvetti MS, Pazzano V, Battipaglia I, Di Mambro C, Calvieri C, Saputo FA, Verticelli L, Carotti A, Torcinaro S, and Drago F

Abstract

Aim: Young patients with operated complex congenital heart defects (CHD) often develop sinus node dysfunction (SND) requiring permanent pacing with rate-responsive function. Activity-driven sensors cannot account for nonmovement stress and cannot modulate heart rate physiologically. Closed Loop Stimulation (CLS, Biotronik, Berlin, Germany) is a physiological rate-responsive pacemaker based on the indirect measure of ventricular contractility. No data are available on the effects of such pacing strategy in young patients., Methods: We report a series of nine patients with CHD and SND who underwent single-chamber CLS-atrial pacing with endocardial or epicardial lead. During the first 30 days, the pacemaker was programmed in AAI pacing mode and then was switched to CLS-atrial pacing mode. An in-hospital control was scheduled 1-2 months later to evaluate the CLS response to neurovegetative stresses (i.e., nonmovement stress [Stroop color test, handgrip] and exercise stress test) and Holter monitor. CLS pacing was compared with rate-responsive accelerometer-driven pacing (AAIR)., Results: At telemetric interrogation, CLS pacing showed a more physiological pattern of 24-h heart rate trends than accelerometer sensors. The data obtained during nonmovement/exercise stress demonstrated a physiological increase in the pacing rate with CLS, in synergy with spontaneous events. The accelerometer sensor histogram, during nonmovement stress, showed a "nonresponse" behavior (only lower rate events), and during exercise test showed most events in lower rate range. Holter monitoring showed increase of average and maximum heart rate compared with AAIR., Conclusion: In young CHD patients, endocardial/epicardial CLS-atrial pacing demonstrated a physiological response of heart rate to neurovegetative and physical stresses., (© 2018 Wiley Periodicals, Inc.)

Published
2018
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23. Voltage gradient mapping and electrophysiologically guided cryoablation in children with AVNRT.

Author

Drago F, Battipaglia I, Russo MS, Remoli R, Pazzano V, Grifoni G, Allegretti G, and Silvetti MS

Subjects
Action Potentials, Adolescent, Adult, Age Factors, Atrioventricular Node physiopathology, Case-Control Studies, Child, Child, Preschool, Female, Heart Rate, Humans, Male, Predictive Value of Tests, Recurrence, Tachycardia, Atrioventricular Nodal Reentry diagnosis, Tachycardia, Atrioventricular Nodal Reentry physiopathology, Time Factors, Treatment Outcome, Young Adult, Atrioventricular Node surgery, Cryosurgery adverse effects, Electrophysiologic Techniques, Cardiac, Tachycardia, Atrioventricular Nodal Reentry surgery
Abstract

Aims: Recently, voltage gradient mapping of Koch's triangle to find low-voltage connections, or 'voltage bridges', corresponding to the anatomic position of the slow pathway, has been introduced as a method to ablate atrioventricular nodal reentry tachycardia (AVNRT) in children. Thus, we aimed to assess the effectiveness of voltage mapping of Koch's triangle, combined with the search for the slow potential signal in 'low-voltage bridges', to guide cryoablation of AVNRT in children., Methods and Results: From June 2015 to May 2016, 35 consecutive paediatric patients (mean age 12.1 ± 4.5 years) underwent 3D-guided cryoablation of AVNRT at our Institution. Fifteen children were enrolled as control group (mean age 14 ± 4 years). A voltage gradient mapping of Koch's triangle was obtained in all patients, showing low-voltage connections in all children with AVNRT but not in controls. Prior to performing cryoablation, we looked for the typical 'hump and spike' electrogram, generally considered to be representative of slow pathway potential within a low-voltage bridge. In all patients the 'hump and spike' electrogram was found inside bridges of low voltage. Focal or high-density linear lesions, extended or not, were delivered guided by low-voltage bridge visualization. Acute success rate was 100%, and no recurrence was reported at a mean follow-up of 8 ± 3 months., Conclusions: Voltage gradient mapping of Koch's triangle, combined with the search for the slow potential signal in low-voltage bridges, is effective in guiding cryoablation of AVNRT in paediatric patients, with a complete acute success rate and no AVNRT recurrences at mid-term follow-up.

Published
2018
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24. What endocardial right ventricular pacing site shows better contractility and synchrony in children and adolescents?

Author

Silvetti MS, Ammirati A, Palmieri R, Pazzano V, Placidi S, Ravà L, Remoli R, Saputo FA, Verticelli L, and Drago F

Subjects
Adolescent, Child, Child, Preschool, Female, Heart Ventricles, Humans, Male, Prosthesis Implantation, Retrospective Studies, Treatment Outcome, Atrioventricular Block physiopathology, Atrioventricular Block therapy, Endocardium physiology, Myocardial Contraction, Pacemaker, Artificial
Abstract

Aims: Right ventricular (RV) apical (RVA) pacing can induce left ventricular (LV) dyssynchrony, remodeling, and dysfunction in children with complete atrioventricular block (CAVB). We compared the functional outcome of RVA with RV alternative pacing sites (RVAPS), including para-Hisian, septal, and outflow tract sites., Methods: This is a single-center, retrospective study. Data were collected before pacemaker implantation (transvenous leads), postoperatively, at 6 months, and at 1-2-3-4 years. Electrocardiogram evaluation included QRS duration, axis, QTc/JTc, and QTc dispersion. Echocardiographic evaluation included 2-D/3-D assessment of ventricular dimensions (Z-score of LV end-diastolic dimension), function (ejection fraction), and synchrony., Results: From 2009 to 2015, 55 patients with CAVB, aged 3-17 years, with or without other congenital heart defects, underwent RVAPS (30 patients, median age 11 years) or RVA (25 patients, median 12 years). All leads were positioned into the septum. Before implantation, no significant differences in parameters were observed, except for higher Z-score in RVAPS than in RVA. After implantation, at a median follow-up of 2.5 (range 1-6) years, the two groups showed no significant differences in LV dimensions, contractility, and synchrony. QRS intervals of RVAPS were significantly shorter than RVA. Clinical status was good and contractility/synchrony indexes were normal or adequate in all patients., Conclusions: In pediatric patients, RVAPS and RVA showed no significant differences in LV dimensions, contractility, and synchrony. Preimplantation dilated patients showed LV reverse remodeling. RVAPS demonstrated shorter QRS intervals. Therefore, septal pacing sites, either RVA or RVAPS, seem to determine good contractility and synchrony at a mid-term follow-up., (© 2017 Wiley Periodicals, Inc.)

Published
2017
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25. Radiofrequency catheter ablation of left-sided accessory pathways in children using a new fluoroscopy integrated 3D-mapping system.

Author

Drago F, Grifoni G, Remoli R, Russo MS, Righi D, Pazzano V, Palmieri R, Placidi S, Saputo FA, and Silvetti MS

Subjects
Action Potentials, Adolescent, Age Factors, Arrhythmias, Cardiac diagnostic imaging, Arrhythmias, Cardiac physiopathology, Catheter Ablation adverse effects, Child, Electrophysiologic Techniques, Cardiac adverse effects, Female, Fluoroscopy, Heart Rate, Humans, Male, Operative Time, Predictive Value of Tests, Radiation Dosage, Radiation Exposure, Radiographic Image Interpretation, Computer-Assisted, Radiography, Interventional adverse effects, Time Factors, Treatment Outcome, Accessory Atrioventricular Bundle, Arrhythmias, Cardiac surgery, Electrophysiologic Techniques, Cardiac methods, Radiography, Interventional methods
Abstract

Introduction: Advances in 3D electroanatomic-mapping technologies have resulted in a safe and effective profile of radiofrequency (RF) catheter ablation. The aim of this study was to evaluate a different catheter ablation approach in patients with left-sided accessory pathways (APs)., Methods and Results: From January 2015 to December 2015, 30 patients (median age 11 years, median weight 45 kg) with manifest or concealed left-sided APs underwent RF catheter ablation with a new protocol. All procedures were performed with the CARTO UNIVU™ system, integrating electroanatomic maps with fluoroscopic views. A 7 Fr ablation catheter was inserted into the right femoral vein and advanced into the right atrium. Geometrical reconstruction and activation map of the right atrium, tricuspid annulus, and coronary sinus were acquired. The ablation catheter was then inserted into the left femoral artery and advanced through the aorta and aortic valve, creating an activation map of the mitral annulus. Catheter ablation was targeted to the site of the earliest activation. No complications occurred. The median procedure and fluoroscopy times were 130 min and 6 s, with a median fluoroscopy dose 0.5 mGy. An average of two catheters was used. Long-term success rate was 97% (29/30) at a median follow-up of 9.6 months. This approach reduced fluoroscopy time, dose and number of catheters used compared with manifest or concealed left-sided AP ablation using CARTO 3™ (P < 0.05)., Conclusions: This new ablation protocol seems to be promising in reducing fluoroscopy exposure and number of catheters used during left-sided AP ablation in children., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)

Published
2017
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26. Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes.

Author

Severino A, Zara C, Campioni M, Flego D, Angelini G, Pedicino D, Giglio AF, Trotta F, Giubilato S, Pazzano V, Lucci C, Iaconelli A, Ruggio A, Biasucci LM, Crea F, and Liuzzo G

Subjects
Acute Coronary Syndrome drug therapy, Blotting, Western, Cells, Cultured, Female, Flow Cytometry, Gene Expression drug effects, Gene Expression Profiling, Humans, Male, Middle Aged, Polymerase Chain Reaction, Acute Coronary Syndrome immunology, Atorvastatin therapeutic use, CD4-Positive T-Lymphocytes drug effects, Early Growth Response Protein 1 biosynthesis, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Lymphocyte Activation drug effects
Abstract

Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 μg/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively). After incubation, we found a significant decrease in interferon-γ-producing CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10-producing CD4+CD25highT-cells (P < 0.001). Atorvastatin increased the expression of 2 genes and decreased the expression of 12 genes (in particular, EGR1, FOS,CCR2 and toll like receptor-4; >3-fold changes).The in-vivo effects of atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels decreased at 48h (P = 0.03).Conclusions-In acute coronary syndromes, the effects of atorvastatin on immune system might be partially related to the inhibition of the master regulator gene EGR1. Our finding might offer a causal explanation on why statins improve the early outcome in acute coronary syndromes.

Published
2017
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27. Role of right ventricular three-dimensional electroanatomic voltage mapping for arrhythmic risk stratification of patients with corrected tetralogy of Fallot or other congenital heart disease involving the right ventricular outflow tract.

Author

Drago F, Pazzano V, Di Mambro C, Russo MS, Palmieri R, Silvetti MS, Giannico S, Leonardi B, Amodeo A, and Di Ciommo VM

Subjects
Adolescent, Adult, Child, Female, Heart Conduction System diagnostic imaging, Heart Defects, Congenital diagnosis, Heart Defects, Congenital physiopathology, Humans, Male, Risk Assessment, Tetralogy of Fallot diagnosis, Ventricular Dysfunction, Right diagnosis, Ventricular Outflow Obstruction diagnosis, Ventricular Outflow Obstruction physiopathology, Young Adult, Body Surface Potential Mapping methods, Heart Conduction System physiopathology, Imaging, Three-Dimensional methods, Tetralogy of Fallot physiopathology, Ventricular Dysfunction, Right physiopathology
Abstract

Background: The post-surgical history of repaired congenital heart disease (rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden death. Electrical myocardial abnormalities could be a substrate for malignant ventricular arrhythmias., Methods and Results: 146 patients with TOF or other rCHD involving a subpulmonary right ventricle, considered to be at high arrhythmic risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM). Maps showed endocardial scars (<0.5mV) in all cases, mainly involving the RV outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved. Total scar extension, expressed as % of total endocardial area, was significantly higher in patients with QRS ≥180ms [4.5% (±2.5) vs 2.8% (±2.4), p=0.014], left and right ventricular systolic dysfunction [4.5% (±3.2) vs 2.8% (±2.3), p=0.016 and 3.5% (±3.0) vs 2.6% (±1.9), p=0.03, respectively], premature ventricular contractions (PVCs) [3.2% (±2.6) vs 2.2% (±1.8), p<0.05], exercise-induced PVCs [3.8% (±2.4) vs 2.6% (±2.2), p=0.01], previous shunt [4.0% (±2.7) vs 2.6% (±2.2), p=0.01] and reintervention [4.2% (±3.2) vs 2.6% (±2.0), p=0.008]. Scar size also showed a positive correlation with duration of post-surgical follow-up (ρ=0.01), age at correction (ρ=0.01) and absolute QRS duration (ρ=0.05)., Conclusions: Patients with rCHD involving the right ventricle show electrical scars with variable distribution, not necessarily matching with sites of surgical lesions. Scar extension correlates with some of the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS. Thus EVM could be considered an additional tool in the assessment of risk stratification in this particular population., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Published
2016
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28. The Need for a Lengthier Cryolesion Can Predict a Worse Outcome in 3D Cryoablation of AV Nodal Slow Pathway in Children.

Author

Drago F, Russo MS, Battipaglia I, Grifoni G, Silvetti MS, Remoli R, Pazzano V, Saputo FA, and Ciani M

Subjects
Adolescent, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Male, Recurrence, Treatment Outcome, Cryosurgery methods, Tachycardia, Atrioventricular Nodal Reentry surgery
Abstract

Background: Transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal reentry tachycardia (AVNRT) in children. Nevertheless, atrioventricular nodal slow-pathway conduction may recur after an acutely successful procedure. The aim of this study was to evaluate the long-term outcome of acutely successful AVNRT cryoablations in pediatric patients in case of focal cryolesion and in case of need for High-Density Linear Lesion (HDLL) cryoablation due to focal failure., Methods: Sixty-nine consecutive pediatric patients (30 males, mean age 12.4 ± 3.2 years; range: 5.4-18.0 years) underwent 3D-guided cryoablation for AVNRT at our institution from July 2013 to November 2014. When a focal cryoablation was acutely unsuccessful, a 3D-guided HDLL was created delivering multiple overlapping cryolesions/cryoenergy applications from the ventricular side of the tricuspid annulus to the atrial side, including the site of focal cryoablation if transiently successful., Results: No permanent cryoablation-related complications occurred. Acute success rate was 98.5% (68 out of 69): in 55.9% (38 out of 68) with focal-lesion and in 44.1% (30 out of 68) with HDLL. Mean follow-up was 25.3 months and AVNRT recurrence rate was 13.2% (nine out of 68): 5.2% (two out of 38) with focal lesion and 23.3% (seven out of 30) with HDLL (P = 0.036)., Conclusions: In cryoablation of AVNRT in children, the need for a more aggressive protocol (HDLL), due to the failure of focal ablation, is strictly related to higher recurrence rates. Indeed, AVNRT recurrences after cryoablation in children seem to be due to a larger and deeper substrate rather than due to the type of energy used., (© 2016 Wiley Periodicals, Inc.)

Published
2016
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29. Predictors of postoperative atrial fibrillation in patients with coronary artery disease undergoing cardiopulmonary bypass: a possible role for myocardial ischemia and atrial inflammation.

Author

Narducci ML, Pelargonio G, Rio T, Leo M, Di Monaco A, Musaico F, Pazzano V, Trotta F, Liuzzo G, Severino A, Biasucci LM, Scapigliati A, Glieca F, Cavaliere F, Rebuzzi AG, Massetti M, and Crea F

Subjects
Aged, Atrial Fibrillation epidemiology, C-Reactive Protein analysis, Female, Fibrinogen analysis, Heart Atria pathology, Humans, Leukocyte Count, Male, Middle Aged, Postoperative Complications epidemiology, Prospective Studies, Risk Factors, Atrial Fibrillation etiology, Cardiopulmonary Bypass adverse effects, Coronary Artery Disease complications, Coronary Artery Disease surgery, Inflammation complications, Myocardial Ischemia complications, Myocarditis complications, Postoperative Complications etiology
Abstract

Objective: To evaluate the preoperative presence of C-reactive protein (CRP) and troponin T(hs-TnT) in patients with coronary artery disease (CAD) undergoing cardiopulmonary bypass (CPB) in order to better clarify the role of atrial inflammation and/or myocardial ischemia in the development of postoperative atrial fibrillation (POAF)., Design: Prospective, nonrandomized study., Setting: University hospital., Participants: Thirty-eight consecutive ischemic patients admitted to the authors' hospital for CAD undergoing elective on-pump coronary artery bypass grafting (CABG)., Intervention: Elective on-pump CABG., Measurements and Main Results: Peripheral blood samples were collected from all patients before and 24 hours after CABG to assess high sensitive (hs)-CRP and troponin T (hs-TnT) levels. The patients' heart rhythm was monitored by continuous ECG telemetry. Biopsies from the right atrial appendage were obtained at the beginning of the CABG procedure in order to perform immunohistochemistry for CRP and reverse transcription polymerase chain reaction for CRP mRNA expression. Fourteen patients out of 38 (36%) developed POAF. Atrial CRP was found in 31 patients (82%), 10 with POAF and 21 with sinus rhythm (71% v 87% respectively, p = ns). None of the atrial samples was positive for CRP mRNA. Atrial CRP did not correlate with serum hs-CRP levels and with occurrence of POAF, but with the incidence of diabetes (p = 0.010). Postoperative hs-TnT levels, but not hs-CRP levels, were identified as the only predictor of POAF occurrence (p = 0.016)., Conclusions: In patients undergoing CABG, neither peripheral nor tissue preoperative CRP levels, but only postoperative hs-TnT levels, correlated with POAF, suggesting the primary role of an ischemic trigger of atrial fibrillation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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30. Inflammatory markers in heart failure: hype or hope?

Author

Cialdella P, Pedicino D, Gustapane M, Santangeli P, Narducci ML, Pelargonio G, Basile E, Giglio AF, Pazzano V, Vitulano N, and Bellocci F

Subjects
Anti-Inflammatory Agents therapeutic use, Biomarkers blood, Cardiovascular Agents therapeutic use, Heart Failure blood, Heart Failure drug therapy, Humans, Inflammation blood, Inflammation drug therapy, Heart Failure immunology, Inflammation immunology, Inflammation Mediators blood
Abstract

Heart failure is a growing global epidemic that involves in its pathophysiology a proinflammatory state. Since the first description of elevated cytokine levels in this setting, there has been increasing interest in understanding the role of these molecules in left-ventricular remodeling and function. Over the years, intense research on the 'cytokine theory' of heart failure has allowed evaluation of the role of inflammatory biomarkers not only as pathogenetic mediators, but also as potential tools in the diagnosis and risk stratification of heart failure patients. Whereas current evidence does not support the use of inflammatory biomarkers for the diagnosis of heart failure, the assessment of their levels and the connection between their changes and changes in clinical status and prognosis has been well validated. At present, the utility of anti-inflammatory therapies in heart failure is still debated, since trials of anti-inflammatory agents in this setting have pointed out controversial results. On the contrary, established treatments of heart failure, including β-blockers, renin-angiotensin system antagonists, and aldosterone-receptor blockers seem able to act by modulating cytokine expression, suggesting a new role for these molecules in guiding heart failure therapy. Therefore, the binomial topic of heart failure and inflammation still has a number of fields not completely explored: our aim is to update current knowledge and future perspectives.

Published
2013
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31. Reversible atrial gap junction remodeling during hypoxia/reoxygenation and ischemia: a possible arrhythmogenic substrate for atrial fibrillation.

Author

Severino A, Narducci ML, Pedicino D, Pazzano V, Giglio AF, Biasucci LM, Liuzzo G, Casella M, Bartoletti S, Dello Russo A, Pelargonio G, Santangeli P, Di Biase L, Natale A, and Crea F

Subjects
Cell Line, Heart Conduction System metabolism, Humans, Myocytes, Cardiac metabolism, Atrial Fibrillation metabolism, Connexin 43 metabolism, Gap Junctions metabolism, Heart Atria metabolism, Myocardial Ischemia metabolism, Myocardial Reperfusion Injury metabolism
Abstract

Alteration of cardiomyocyte gap-junctions and component connexins (Cx) has been suggested to contribute to the development of atrial fibrillation (AF), including postoperative AF. We tested different possible stimuli, such as hypoxia and ischemia, influencing Cx43 and Cx40 expression and distribution in cultured atrial cells (HL-1) and reversibility of these processes after reoxygenation. Western-blot analysis and immunostaining using anti-Cx43, anti-Cx40 and anti-zonula occludens polyclonal antibodies were performed. HL-1 cells exposed to hypoxia for 24 and 48 h showed a reduction of Cx43 protein levels by 75% and 90% respectively (p < 0.001). During reoxygenation following 24 h of hypoxia, Cx43 levels increased to reach the basal level within 48 h, while they remained at low level during reoxygenation following 48 h of hypoxia. Furthermore, atrial cardiomyocytes subjected to simulated ischemia (SI) were incubated in normoxic and hypoxic conditions for 3, 6, 9, 12 h. Atrial cardiomyocytes subjected to SI in addition to normoxia showed a progressive reduction of Cx43 levels beginning from 3 h. During SI and hypoxia, atrial Cx43 levels showed an initial decrease after 3 h with a subsequent rescue beginning from 6 h of exposure (p = 0.001). Hypoxia and ischemia per se downregulate Cx43 protein expression in atrial cardiomyocytes, but protein downregulation is reversible, depending on hypoxia duration and the association of the two triggers. These alterations characterize several conditions and might contribute to the generation of an arrhythmogenic substrate leading to AF onset and/or maintenance.

Published
2012
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32. CD4+CD28 null T lymphocytes are expanded in young women with polycystic ovary syndrome.

Author

Niccoli G, Apa R, Lanzone A, Liuzzo G, Spaziani C, Sagnella F, Cosentino N, Moro F, Martinez D, Morciano A, Bacà M, Pazzano V, Gangale MF, Tropea A, and Crea F

Subjects
Adolescent, Adult, Analysis of Variance, Biomarkers blood, C-Reactive Protein analysis, Case-Control Studies, Female, Humans, Hyperinsulinism immunology, Inflammation Mediators blood, Italy, Linear Models, Polycystic Ovary Syndrome complications, Risk Assessment, Risk Factors, Young Adult, CD28 Antigens metabolism, CD4-Positive T-Lymphocytes immunology, Cardiovascular Diseases immunology, Cell Proliferation, Polycystic Ovary Syndrome immunology
Abstract

Women affected by polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. We demonstrated that women with PCOS showed an expansion of CD4(+)CD28(null) T cells, an aggressive population of T lymphocytes that has been recently associated with recurrent coronary instability and type 2 diabetes mellitus. This sheds new light on possible mechanisms responsible for the higher rate of cardiovascular disease among women with PCOS., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Published
2011
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33. Expansion of CD4+CD28null T-lymphocytes in diabetic patients: exploring new pathogenetic mechanisms of increased cardiovascular risk in diabetes mellitus.

Author

Giubilato S, Liuzzo G, Brugaletta S, Pitocco D, Graziani F, Smaldone C, Montone RA, Pazzano V, Pedicino D, Biasucci LM, Ghirlanda G, and Crea F

Subjects
Acute Coronary Syndrome drug therapy, Age Factors, Aged, Analysis of Variance, CD28 Antigens immunology, CD4-Positive T-Lymphocytes physiology, Case-Control Studies, Diabetes Mellitus, Type 2 drug therapy, Diabetic Angiopathies drug therapy, Disease-Free Survival, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Kaplan-Meier Estimate, Lymphocytes, Null physiology, Male, Middle Aged, Risk Factors, T-Lymphocyte Subsets physiology, Acute Coronary Syndrome immunology, Diabetes Mellitus, Type 2 immunology, Diabetic Angiopathies immunology, T-Lymphocytes physiology
Abstract

Aims: Diabetes mellitus (DM) is associated with high incidence of first and recurrent cardiovascular events, especially acute coronary syndromes (ACSs); however, the mechanisms involved are still unknown. We sought to investigate the role of CD4(+)CD28(null)T-lymphocytes, a rare long-lived subset of T-lymphocytes with proatherogenic and plaque-destabilizing properties, in the increased cardiovascular risk associated with DM., Methods and Results: CD4(+)CD28(null)T-cell frequency was analysed by flow-cytometry in 60 DM patients without overt cardiovascular disease (cDM), in 166 ACS patients with or without DM (ACS/DM+, n= 51 and ACS/DM-, n= 115), and in 60 healthy individuals. The incidence of cardiovascular events (death, myocardial infarction, unstable angina) was assessed at 36 months follow-up. CD4+CD28(null)T-cell frequency (median, range) was higher in ACS/DM+ (12.7%, 0.1-48) vs. ACS/DM- (3.9%, 0.2-35), cDM (3.1%, 0.3-22.4), and controls (1.5%, 0.1-9.1) (P< 0.001 for all comparisons). Notably, cDM patients had significantly higher CD4+CD28(null)T-cell frequency than controls (P= 0.001). Glycosylated haemoglobin A(1c) was the only parameter independently associated with CD4+CD28(null)T-cells in cDM. The 36-month event-free survival was significantly lower in cDM patients with CD4+CD28(null)T-cells ≥4% (90th percentile of normal distribution) than in those with CD4+CD28(null)T-cells <4% (P= 0.039). Among ACS patients, the 36-month event-free survival was the lowest in those with DM and CD4+CD28(null)T-cells ≥4% and highest in those without DM and CD4+CD28(null)T-cells <4% (P< 0.001), being intermediate in those with only one of these features., Conclusions: In DM patients, CD4+CD28(null)T-cells are expanded and are associated with poor glycaemic control; they also correlate with the occurrence of a first cardiovascular event and with a worse outcome after an ACS.

Published
2011
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34. Human epicardium-derived cells fuse with high efficiency with skeletal myotubes and differentiate toward the skeletal muscle phenotype: a comparison study with stromal and endothelial cells.

Author

Gentile A, Toietta G, Pazzano V, Tsiopoulos VD, Giglio AF, Crea F, Pompilio G, Capogrossi MC, and Di Rocco G

Subjects
Animals, Cell Fusion, Cell Nucleus metabolism, Cellular Reprogramming genetics, Coculture Techniques, Dystrophin metabolism, Endothelial Cells metabolism, Endothelial Cells transplantation, Gene Expression Regulation, Gene Knockdown Techniques, Humans, Interleukin-13 metabolism, Interleukin-4 metabolism, Mesoderm cytology, Mice, Mice, Inbred mdx, Muscle Fibers, Skeletal metabolism, MyoD Protein metabolism, Myoblasts cytology, Myoblasts metabolism, Organ Specificity genetics, Phenotype, Receptors, Interleukin-4 metabolism, Stromal Cells cytology, Stromal Cells metabolism, Stromal Cells transplantation, Vascular Cell Adhesion Molecule-1 metabolism, Cell Differentiation, Endothelial Cells cytology, Muscle Fibers, Skeletal cytology, Muscle, Skeletal cytology, Pericardium cytology
Abstract

Recent studies have underscored a role for the epicardium as a source of multipotent cells. Here, we investigate the myogenic potential of adult human epicardium-derived cells (EPDCs) and analyze their ability to undergo skeletal myogenesis when cultured with differentiating primary myoblasts. Results are compared to those obtained with mesenchymal stromal cells (MSCs) and with endothelial cells, another mesodermal derivative. We demonstrate that EPDCs spontaneously fuse with pre-existing myotubes with an efficiency that is significantly higher than that of other cells. Although at a low frequency, endothelial cells may also contribute to myotube formation. In all cases analyzed, after entering the myotube, nonmuscle nuclei are reprogrammed to express muscle-specific genes. The fusion competence of nonmyogenic cells in vitro parallels their ability to reconstitute dystrophin expression in mdx mice. We additionally show that vascular cell adhesion molecule 1 (VCAM1) expression levels of nonmuscle cells are modulated by soluble factors secreted by skeletal myoblasts and that VCAM1 function is required for fusion to occur. Finally, treatment with interleukin (IL)-4 or IL-13, two cytokines released by differentiating myotubes, increases VCAM1 expression and enhances the rate of fusion of EPDCs and MSCs, but not that of endothelial cells.

Published
2011
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35. Chlamydia pneumoniae in coronary atherosclerotic plaques and coronary instability.

Author

Liuzzo G, Ciervo A, Niccoli G, Mancini F, Fusco B, Montone RA, Pazzano V, Pedicino D, Galiffa VA, Graziani F, Biasucci LM, Mongiardo R, Cassone A, and Crea F

Subjects
Aged, Chlamydophila Infections microbiology, Female, Humans, Male, Middle Aged, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome microbiology, Chlamydophila Infections diagnosis, Chlamydophila pneumoniae isolation & purification, Plaque, Atherosclerotic diagnosis, Plaque, Atherosclerotic microbiology
Published
2011
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36. Immunomodulator activity of 3-hydroxy-3-methilglutaryl-CoA inhibitors.

Author

Smaldone C, Brugaletta S, Pazzano V, and Liuzzo G

Subjects
Clinical Trials as Topic, Humans, Inflammation drug therapy, Membranes drug effects, Prenylation drug effects, Autoimmune Diseases drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Immunologic Factors pharmacology, Immunologic Factors therapeutic use, Immunomodulation drug effects
Abstract

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA are best known for their lipid-lowering effects but they also possess immunomodulatory properties that are, at least in part, independent of changes in serum cholesterol. Some recent clinical trials (eg. PROVE-IT) have shown that statins exert beneficial cardiovascular effects independently of the resultant level of LDL cholesterol. These "pleiotropic" effects seem to be due to inhibition of prenylation of several proteins such as the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins are able to modulate immune responses by modulating cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Over the past decade, a large number of studies reported a prominent role of inflammation and immune response in atherosclerosis, thus, the ability of statins to modulate immune-inflammatory processes could explain their cardiovascular beneficial effects beyond lipid-lowering effects. Moreover, various studies demonstrated beneficial effects of statins in inflammatory and auto-immune diseases, such as rheumatoid arthritis, multiple sclerosis and others. The purpose of this review is to summarize clinical and experimental evidence of immunomodulatory properties of these drugs, highlighting their clinical and, thus, therapeutic implications.

Published
2009
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