85 results on '"Bloise R"'
Search Results
2. Electrical storm in a Brugada syndrome population: efficacy of oral hydroquinidine treatment
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Sciarra, L., Bloise, R., Allocca, G., Marras, E., Lioy, E., Delise, P., Priori, S., and Caloʼ, L.
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- 2011
3. Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1
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Mazzanti, A. Guz, D. Trancuccio, A. Pagan, E. Kukavica, D. Chargeishvili, T. Olivetti, N. Biernacka, E.K. Sacilotto, L. Sarquella-Brugada, G. Campuzano, O. Nof, E. Anastasakis, A. Sansone, V.A. Jimenez-Jaimez, J. Cruz, F. Sánchez-Quiñones, J. Hernandez-Afonso, J. Fuentes, M.E. Średniawa, B. Garoufi, A. Andršová, I. Izquierdo, M. Marinov, R. Danon, A. Expósito-García, V. Garcia-Fernandez, A. Muñoz-Esparza, C. Ortíz, M. Zienciuk-Krajka, A. Tavazzani, E. Monteforte, N. Bloise, R. Marino, M. Memmi, M. Napolitano, C. Zorio, E. Monserrat, L. Bagnardi, V. Priori, S.G.
- Abstract
Background: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. Objectives: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. Methods: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. Results: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). Conclusions: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1. © 2020
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- 2020
4. Poster session Friday 7 December - PM: Effect of systemic illnesses on the heart
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Monteforte, N, Bloise, R, Napolitano, C, and Priori, SG
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- 2012
5. Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk
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Mazzanti, A, Ng, K, Faragli, A, Maragna, R, Chiodaroli, E, Orphanou, N, Monteforte, N, Memmi, M, Gambelli, P, Novelli, V, Bloise, R, Catalano, O, Moro, G, Tibollo, V, Morini, M, Bellazzi, R, Napolitano, C, Priori, S., BAGNARDI, VINCENZO, Mazzanti, A, Ng, K, Faragli, A, Maragna, R, Chiodaroli, E, Orphanou, N, Monteforte, N, Memmi, M, Gambelli, P, Novelli, V, Bloise, R, Catalano, O, Moro, G, Tibollo, V, Morini, M, Bellazzi, R, Napolitano, C, Bagnardi, V, and Priori, S
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implantable cardioverter-defibrillator ,athlete ,ventricular tachycardia ,genetic ,sudden cardiac death - Abstract
Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined. Objectives This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy. Methods We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals. Results A first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated. Conclusions The high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.
- Published
- 2016
6. Efficacy of a biological therapy for recessive Catecholaminergic Polymorphic Ventricular Tachycardia in human induced pluripotent stem cells-derived cardiomyocytes
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Lodola F, Di Pasquale E, Bongianino R, Denegri M, Rutigliano L, Buonocore M, Bloise R, Condorelli G, Napolitano C, Priori SG, Lodola, F, Di Pasquale, E, Bongianino, R, Denegri, M, Rutigliano, L, Buonocore, M, Bloise, R, Condorelli, G, Napolitano, C, and Priori, S
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Cardiac arrhythmias, gene therapy, physiology ,Cardiac arrhythmias, gene therapy, CPVT, hiPS-CMs - Published
- 2015
7. CaMKII inhibition in human induced pluripotent stem cells derived from Catecholaminergic polymorphic ventricular tachycardia patients
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Lodola F, Di Pasquale E, Novelli V, Denegri M, Avelino-Cruz JE, Curcio A, Bongianino R, Leccioli V, Buonocore M, Bloise R, Condorelli G, Napolitano C, Priori SG, Lodola, F, Di Pasquale, E, Novelli, V, Denegri, M, Avelino-Cruz, J, Curcio, A, Bongianino, R, Leccioli, V, Buonocore, M, Bloise, R, Condorelli, G, Napolitano, C, and Priori, S
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CaMKII, human induced pluripotent stem cells cardiomyocytes, Catecholaminergic polymorphic ventricular tachycardia - Published
- 2012
8. The role of neonatal electrocardiography in the early identification of genetic arrhythmogenic disorders and congenital cardiovascular diseases: prospective data from 25865 infants
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Salice, P., Stramba Badiale, M., Mosca, F., Gioventu, M., Bosi, G., Priori, S.G., Bloise, R., Crotti, L., Fesslova, V., Mannarino, S., and Schwartz, P.J.
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Settore MED/38 - Pediatria Generale e Specialistica - Published
- 2005
9. I-12 Timothy Syndrome and Cardiomyopathy
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Bloise, R.
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Lectures by Invited Speakers - Published
- 2011
10. CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia.
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Di Pasquale, E., Lodola, F., Miragoli, M., Denegri, M., Avelino-Cruz, J. E., Buonocore, M., Nakahama, H., Portararo, P., Bloise, R., Napolitano, C., Condorelli, G., and Priori, S. G.
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- 2013
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11. Sudden cardiac death and genetic ion channelopathies: long QT, Brugada, short QT, catecholaminergic polymorphic ventricular tachycardia, and idiopathic ventricular fibrillation.
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Napolitano C, Bloise R, Monteforte N, Priori SG, Napolitano, Carlo, Bloise, Raffaella, Monteforte, Nicola, and Priori, Silvia G
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- 2012
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12. Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients.
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Ruan Y, Liu N, Bloise R, Napolitano C, Priori SG, Ruan, Yanfei, Liu, Nian, Bloise, Raffaella, Napolitano, Carlo, and Priori, Silvia G
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- 2007
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13. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers.
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Priori SG, Napolitano C, Schwartz PJ, Grillo M, Bloise R, Ronchetti E, Moncalvo C, Tulipani C, Veia A, Bottelli G, Nastoli J, Priori, Silvia G, Napolitano, Carlo, Schwartz, Peter J, Grillo, Massimiliano, Bloise, Raffaella, Ronchetti, Elena, Moncalvo, Cinzia, Tulipani, Chiara, and Veia, Alessia
- Abstract
Context: Data on the efficacy of beta-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.Objective: To describe and assess outcome in a large systematically genotyped population of beta-blocker-treated LQTS patients.Design, Setting, and Patients: Consecutive LQTS-genotyped patients (n = 335) in Italy treated with beta-blockers for an average of 5 years.Main Outcome Measures: Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received beta-blocker therapy according to genotype.Results: Cardiac events among patients receiving beta-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P =.001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from beta-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P =.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).Conclusion: Among patients with genetic LQTS treated with beta-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes. [ABSTRACT FROM AUTHOR]- Published
- 2004
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14. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome.
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Schwartz PJ, Priori SG, Cerrone M, Spazzolini C, Odero A, Napolitano C, Bloise R, De Ferrari GM, Klersy C, Moss AJ, Zareba W, Robinson JL, Hall WJ, Brink PA, Toivonen L, Epstein AE, Li C, and Hu D
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- 2004
15. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia.
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Priori, S G, Napolitano, C, Tiso, N, Memmi, M, Vignati, G, Bloise, R, Sorrentino, V, and Danieli, G A
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- 2001
16. The long QT syndrome.
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Priori, S. G., Bloise, R., and Crotti, L.
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- 2001
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17. Catecholaminergic polymorphic ventricular tachycardia: successful emergency treatment with intravenous propranolol.
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De Rosa G, Delogu AB, Piastra M, Chiaretti A, Bloise R, Priori SG, De Rosa, Gabriella, Delogu, Angelica B, Piastra, Marco, Chiaretti, Antonio, Bloise, Raffaella, and Priori, Silvia G
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- 2004
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18. The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge.
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Priori, S G, Napolitano, C, Schwartz, P J, Bloise, R, Crotti, L, and Ronchetti, E
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- 2000
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19. Beyond LQT3 and brugada syndrome: The search for the overlapping phenotypes.
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Grillo, M, Napolitano, C, Schwartz, PJ, Bloise, R, Ronchetti, E, and Priori, SG
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- 2000
20. Stability of ethylxanthate ion in neutral and weakly acidic media. Part 1: Influence of pH
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Maillot, M., Cecile, J.-L., and Bloise, R.
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- 1984
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21. Slag-metal equilibrium in the ferromanganese blast furnace
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Bloise, R.
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- 1990
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22. Molecular diagnosis in a child with sudden infant death syndrome.
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Schwartz PJ, Priori SG, Bloise R, Napolitano C, Ronchetti E, Piccinini A, Goj C, Breithardt G, Schulze-Bahr E, Wedekind H, and Nastoli J
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- 2001
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23. Risk stratification in the long-QT syndrome.
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Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D, Priori, Silvia G, Schwartz, Peter J, Napolitano, Carlo, Bloise, Raffaella, Ronchetti, Elena, Grillo, Massimiliano, Vicentini, Alessandro, and Spazzolini, Carla
- Abstract
Background: Mutations in potassium-channel genes KCNQ1 (LQT1 locus) and KCNH2 (LQT2 locus) and the sodium-channel gene SCN5A (LQT3 locus) are the most common causes of the long-QT syndrome. We stratified risk according to the genotype, in conjunction with other clinical variables such as sex and the length of the QT interval.Methods: We evaluated 647 patients (386 with a mutation at the LQT1 locus, 206 with a mutation at the LQT2 locus, and 55 with a mutation at the LQT3 locus) from 193 consecutively genotyped families with the long-QT syndrome. The cumulative probability of a first cardiac event, defined as the occurrence of syncope, cardiac arrest, or sudden death before the age of 40 years and before the initiation of therapy, was determined according to genotype, sex, and the QT interval corrected for heart rate (QTc). Within each genotype we also assessed risk in the four categories derived from the combination of sex and QTc (<500 msec or > or =500 msec).Results: The incidence of a first cardiac event before the age of 40 years and before the initiation of therapy was lower among patients with a mutation at the LQT1 locus (30 percent) than among those with a mutation at the LQT2 locus (46 percent) or those with a mutation at the LQT3 locus (42 percent) (P<0.001 by Fisher's exact test). Multivariate analysis showed that the genetic locus and the QTc, but not sex, were independent predictors of risk. The QTc was an independent predictor of risk among patients with a mutation at the LQT1 locus and those with a mutation at the LQT2 locus but not among those with a mutation at the LQT3 locus, whereas sex was an independent predictor of events only among those with a mutation at the LQT3 locus.Conclusions: The locus of the causative mutation affects the clinical course of the long-QT syndrome and modulates the effects of the QTc and sex on clinical manifestations. We propose an approach to risk stratification based on these variables. [ABSTRACT FROM AUTHOR]- Published
- 2003
24. Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome
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Nicola Monteforte, Mirella Memmi, Raffaella Bloise, Alberto Malovini, Carlo Napolitano, Vincenzo Bagnardi, L. Braghieri, Silvia G. Priori, Massimo Morini, Gaetano Vacanti, Eleonora Pagan, Andrea Mazzanti, Patrick Gambelli, Luciana Sacilotto, Lorenzo Monserrat, Martín Ortiz, Riccardo Maragna, Maira Marino, Riccardo Bellazzi, Ministero della Salute (Italia), Mazzanti, A, Maragna, R, Vacanti, G, Monteforte, N, Bloise, R, Marino, M, Braghieri, L, Gambelli, P, Memmi, M, Pagan, E, Morini, M, Malovini, A, Ortiz, M, Sacilotto, L, Bellazzi, R, Monserrat, L, Napolitano, C, Bagnardi, V, Priori, S, and Italian Ministry of Health
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Male ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Genotype ,Long QT syndrome ,030204 cardiovascular system & hematology ,QT interval ,Risk Assessment ,sudden cardiac death ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Nadolol ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,cardiovascular diseases ,Proportional hazards model ,business.industry ,life-threatening arrhythmic event ,Hazard ratio ,Heart ,medicine.disease ,inherited arrhythmia ,Confidence interval ,Long QT Syndrome ,beta-blocker ,Cardiology ,Female ,genetic ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,medicine.drug - Abstract
Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers. The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03). The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS. This work was supported by the Ricerca Corrente funding scheme of the Italian Ministry of Health. Dr. Ortiz has received personal fees from Health in Code, SL. Dr. Monserrat is a shareholder in Health in Code, SL. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí
- Published
- 2018
25. The Long QT Syndrome
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Silvia G. Priori, Lia Crotti, Raffaella Bloise, Priori, S, Bloise, R, and Crotti, L
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medicine.medical_specialty ,ERG1 Potassium Channel ,Potassium Channels ,Sympathetic Nervous System ,medicine.medical_treatment ,Long QT syndrome ,Adrenergic beta-Antagonists ,Electric Countershock ,Disease ,Sudden death ,Diagnosis, Differential ,Electrocardiography ,Transcriptional Regulator ERG ,Heart Rate ,Physiology (medical) ,Internal medicine ,Heart rate ,medicine ,Humans ,Genetic Predisposition to Disease ,Sympathectomy ,Cation Transport Proteins ,Molecular Biology ,Normal heart ,medicine.diagnostic_test ,business.industry ,Cardiac Pacing, Artificial ,Periodic paralysis ,MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,medicine.disease ,Implantable cardioverter-defibrillator ,Ether-A-Go-Go Potassium Channels ,DNA-Binding Proteins ,Long QT Syndrome ,Endocrinology ,Potassium Channels, Voltage-Gated ,Cardiology ,Trans-Activators ,Cardiology and Cardiovascular Medicine ,business - Abstract
The Long QT syndrome (LQTS) is an inherited arrhythmogenic disease occurring in the structurally normal heart that may cause sudden death and that usually manifests in children and teen-agers (1). The prevalence of this disorder is still undefined, however it is estimated to be between 1:10000–1:5000.
- Published
- 2001
26. CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia
- Author
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Carlo Napolitano, Gianluigi Condorelli, Hiroko Nakahama, José Everardo Avelino-Cruz, E Di Pasquale, P Portararo, M Buonocore, Raffaella Bloise, Francesco Lodola, Marco Denegri, Michele Miragoli, Silvia G. Priori, Di Pasquale, E, Lodola, F, Miragoli, M, Denegri, M, Avelino-Cruz, J, Buonocore, M, Nakahama, H, Portararo, P, Bloise, R, Napolitano, C, Condorelli, G, and Priori, S
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Tachycardia ,calcium/calmodulin pathway ,Male ,Cancer Research ,Benzylamines ,cardiomyocytes ,030204 cardiovascular system & hematology ,Pharmacology ,Ryanodine receptor 2 ,Mice ,0302 clinical medicine ,Myocyte ,Myocytes, Cardiac ,Induced pluripotent stem cell ,Child ,Catecholaminergic ,0303 health sciences ,Sulfonamides ,Ryanodine receptor ,Cell Differentiation ,3. Good health ,Pedigree ,Phenotype ,Child, Preschool ,cardiovascular system ,Original Article ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Adolescent ,induced pluripotent stem cells ,CPVT ,Immunology ,Molecular Sequence Data ,Biology ,Catecholaminergic polymorphic ventricular tachycardia ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Ca2+/calmodulin-dependent protein kinase ,Internal medicine ,Receptors, Adrenergic, beta ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,030304 developmental biology ,Base Sequence ,Arrhythmias, Cardiac ,Ryanodine Receptor Calcium Release Channel ,Cell Biology ,CaMKII inhibition, arrhythmas, Catecholaminergic Polymorphic Ventricular Tachycardia, hiPSC-CMs ,medicine.disease ,Endocrinology ,HEK293 Cells ,Tachycardia, Ventricular ,Calcium ,diseases modeling ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 - Abstract
Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after beta-adrenergic stimulation, resembling the cardiac phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), an antiarrhythmic drug that inhibits Ca2+/calmodulin-dependent serine-threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.
- Published
- 2013
27. The Impact of a Neurocritical Care and Neuropalliative Collaboration on Intensive Care Unit Outcomes.
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Shemme AJ, Phillips JN, Bloise R, Koehler TJ, Gorelick PB, and Francis BA
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- Cohort Studies, Hospital Mortality, Humans, Length of Stay, Retrospective Studies, Hospitalization, Intensive Care Units
- Abstract
Background: Neurocritical care (NCC) and neuropalliative care (NPC) clinicians provide care in specialized intensive care units (ICU). There is a paucity of data regarding the impact of NCC and NPC collaboration in smaller, community-focused settings., Objective: To determine the clinical impact of introducing a NCC/NPC collaborative model in a mixed ICU community-based teaching hospital., Design: Retrospective pre/post cohort study., Subjects: Patients ≥18 years of age admitted to the ICU who received neurology and palliative care consultations between September 1, 2015 and August 31, 2017 at a 300 bed community-focused hospital were included., Intervention: The addition of a NCC/NPC collaborative model took place in September of 2016. The time periods before (9/1/2015 to 8/31/2016) and after (9/1/2016 to 8/31/2017) the addition were compared., Results: A total of 274 admissions (pre: 130, post: 144) were included. There were significantly more NCC consultations provided in the post-period (44.6% vs 57.6%; P = .03). NPC consultation increased (55.4% vs 66.7%; P = .056) Median LOS was significantly shorter after implementation of the collaborative model (11 vs 8 days; P = .01). Median ICU LOS was also shorter by 1 ICU-day in the post-period, though this was not statistically significant ( P = .23). Mortality rates were similar ( P = .95)., Conclusions: Our findings suggest NCC/NPC collaboration in a community-focused teaching hospital was associated with more NCC consultations, as well as shorter LOS without increasing mortality. These data highlight the importance of supporting collaborative models of care in community settings. Further research is warranted.
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- 2022
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28. Role of CACNA1C in Brugada syndrome: Prevalence and phenotype of probands referred for genetic testing.
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Novelli V, Memmi M, Malovini A, Mazzanti A, Liu N, Yanfei R, Bongianino R, Denegri M, Monteforte N, Bloise R, Morini M, and Napolitano C
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- Calcium Channels, L-Type genetics, Genetic Testing, Humans, Mutation, NAV1.5 Voltage-Gated Sodium Channel genetics, Phenotype, Prevalence, Brugada Syndrome diagnosis, Brugada Syndrome epidemiology, Brugada Syndrome genetics
- Abstract
Background: Evidence for the role of the CACNA1C gene, which encodes for the α-subunit of the cardiac L-type calcium channel CaV1.2, as a cause of the BrS3 variant of Brugada syndrome (BrS) is contradictory., Objective: The purpose of this study was to define in a large BrS cohort the yield of molecular screening and to test whether appropriate patient selection could improve clinical utility., Methods: A total of 709 patients were included in this study. BrS probands (n = 563, consecutively referred) underwent CACNA1C sequencing. Two matched cohorts where defined: discovery cohort (n = 200) and confirmation cohort (n = 363). In addition, the clinical phenotypes of a matched SCN5A-positive BrS cohort (n = 146) were included for comparative genotype-phenotype correlation., Results: In the discovery cohort, we identified 11 different rare variants in 9 patients; 10 of the variants (5%) were considered potentially causative based on their frequency in the general population. However, American College of Medical Genetics criteria were unable to classify the majority (80%) of them, which eventually were labeled as variants of unknown significance (VUS). Functional studies revealed a loss of function for 9 variants, pointing to a prevalence of CACNA1C causative variants in 4% of the discovery cohort. Genotype-phenotype correlation showed that pathogenic variants are significantly more frequent in patients with shorter QTc (12.9% vs 2.2% in patients with QTc <390 ms)., Conclusion: CACNA1C is an infrequent but definitive cause of BrS typically associated with short QT. Functional studies are highly relevant to improve variant interpretation., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
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- 2022
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29. Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers.
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Mazzanti A, Kukavica D, Trancuccio A, Memmi M, Bloise R, Gambelli P, Marino M, Ortíz-Genga M, Morini M, Monteforte N, Giordano U, Keegan R, Tomasi L, Anastasakis A, Davis AM, Shimizu W, Blom NA, Santiago DJ, Napolitano C, Monserrat L, and Priori SG
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- Adolescent, Adrenergic beta-Antagonists therapeutic use, Adult, Child, Cohort Studies, Electrocardiography, Female, Humans, Male, Prospective Studies, Ryanodine Receptor Calcium Release Channel genetics, Syncope, Young Adult, Nadolol therapeutic use, Tachycardia, Ventricular diagnosis
- Abstract
Importance: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite β-blocker treatment. Further complicating management, the role of implantable cardioverter defibrillator (ICD) in CPVT is debated., Objective: To investigate the long-term outcomes of patients with RYR2 CPVT treated with β-blockers only and the cost to benefit ratio of ICD., Design, Settings, and Participants: This prospective cohort study conducted from January 1988 to October 2020 with a mean (SD) follow-up of 9.4 (7.5) years included patients who were referred to the Molecular Cardiology Clinics of ICS Maugeri Hospital, Pavia, Italy. Participants included consecutive patients with CPVT who were carriers of a pathogenic or likely pathogenic RYR2 variant with long-term clinical follow-up., Exposures: Treatment with selective and nonselective β-blocker only and ICD implant when indicated., Main Outcome and Measures: The main outcome was the occurrence of the first LTAE while taking a β-blocker. LTAE was defined as a composite of 3 hard end points: sudden cardiac death, aborted cardiac arrest, and hemodynamically nontolerated ventricular tachycardia., Results: The cohort included 216 patients with RYR2 CPVT (121 of 216 female [55%], median [IQR] age 14, [9-30] years). During a mean (SD) follow-up of 9.4 (7.5) years taking β-blockers only, 28 of 216 patients (13%) experienced an LTAE (annual rate, 1.9%; 95% CI, 1.3-2.7). In multivariable analysis, experiencing either an LTAE (hazard ratio [HR], 3.3; 95% CI, 1.2-8.9; P = .02) or syncope before diagnosis (HR, 4.5; 95% CI, 1.8-11.1; P = .001) and carrying a C-terminal domain variant (HR, 18.1; 95% CI, 4.1-80.8; P < .001) were associated with an increased LTAE risk during β-blocker therapy only. The risk of LTAE among those taking selective β-blockers vs nadolol was increased 6-fold (HR, 5.8; 95% CI, 2.1-16.3; P = .001). Conversely, no significant difference was present between propranolol and nadolol (HR, 1.8; 95% CI, 0.4-7.3; P = .44). An ICD was implanted in 79 of 216 patients (37%) who were followed up for a mean (SD) of 8.6 (6.3) years. At the occurrence of LTAE, ICD carriers were more likely to survive (18 of 18 [100%]) than non-ICD carriers (6 of 10 [60%]; P = .01)., Conclusions and Relevance: In this cohort study, selective β-blockers were associated with a higher risk of LTAE as compared with nadolol. Independently from treatment, LTAE and syncope before diagnosis and C-terminal domain variants identified patients at higher risk of β-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT.
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- 2022
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30. Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy.
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Curcio A, Malovini A, Mazzanti A, Memmi M, Gambelli P, La Rosa F, Bloise R, Indolfi C, Bellazzi R, and Napolitano C
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- Adult, Atrioventricular Block epidemiology, Brugada Syndrome epidemiology, Death, Sudden, Cardiac epidemiology, Electrocardiography, Female, Follow-Up Studies, Genotype, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Pedigree, Phenotype, Retrospective Studies, Young Adult, Atrioventricular Block genetics, Brugada Syndrome genetics, Death, Sudden, Cardiac etiology, Mutation, NAV1.5 Voltage-Gated Sodium Channel genetics
- Abstract
Background: The genetic architecture of Brugada syndrome (BrS) is emerging as an increasingly complex area of investigation. The identification of genetically homogeneous populations can provide mechanistic insights and improve genotype-phenotype correlation., Objective: To characterize and define the clinical implications of a novel BrS founder mutation. Using a haplotype-based approach we investigated whether 2 SCN5A genetic variants could derive from founder events., Methods: Single nucleotide polymorphisms were genotyped in 201 subjects, haplotypes reconstructed, and mutational age estimated. Clinical phenotypes and historical records were collected., Results: A SCN5A variant (c.3352C>T; p.Gln1118Ter) was identified in 3 probands with BrS originating from south Italy. The same mutation was identified in a proband from central Italy and in 1 U.S. resident subject with Italian ancestry. The 5 individuals carried a common core haplotype, whose frequency was extremely low in local noncarrier probands and in population controls (0%-6.06%). The clinical presentation included multigenerational dominant transmission of Brugada electrocardiographic pattern, high incidence of sudden cardiac death (SCD), and cardiac conduction defects (CCD). We reconstructed 7-generation pedigrees with common geographic origin. Variant's age estimates suggested that origin of the p.Gln1118Ter dates back 76 generations (95% confidence interval: 28-200). A second SCN5A variant (c.5350G>A; p.Glu1784Lys) identified in the region did not show similar founder signal., Conclusion: p.Gln1118Ter is a novel BrS/CCD/SCD founder mutation. We illustrate how these findings provide insights on the inheritance patterns and phenotypes associated with SCN5A mutation., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
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- 2021
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31. Association of Hydroxychloroquine With QTc Interval in Patients With COVID-19.
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Mazzanti A, Briani M, Kukavica D, Bulian F, Marelli S, Trancuccio A, Monteforte N, Manciulli T, Morini M, Carlucci A, Viggiani G, Cannata F, Negri S, Bloise R, Memmi M, Gambelli P, Carbone A, Molteni M, Bianchini R, Salgarello R, Sozzi S, De Cata P, Fanfulla F, Ceriana P, Locatelli C, Napolitano C, Chiovato L, Tomasi L, Stefanini GG, Condorelli G, and Priori SG
- Subjects
- Aged, Aged, 80 and over, COVID-19 epidemiology, COVID-19 virology, Electrocardiography methods, Female, Humans, Long QT Syndrome epidemiology, Male, Middle Aged, Hydroxychloroquine pharmacology, Long QT Syndrome drug therapy, COVID-19 Drug Treatment
- Published
- 2020
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32. Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.
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Mazzanti A, Guz D, Trancuccio A, Pagan E, Kukavica D, Chargeishvili T, Olivetti N, Biernacka EK, Sacilotto L, Sarquella-Brugada G, Campuzano O, Nof E, Anastasakis A, Sansone VA, Jimenez-Jaimez J, Cruz F, Sánchez-Quiñones J, Hernandez-Afonso J, Fuentes ME, Średniawa B, Garoufi A, Andršová I, Izquierdo M, Marinov R, Danon A, Expósito-García V, Garcia-Fernandez A, Muñoz-Esparza C, Ortíz M, Zienciuk-Krajka A, Tavazzani E, Monteforte N, Bloise R, Marino M, Memmi M, Napolitano C, Zorio E, Monserrat L, Bagnardi V, and Priori SG
- Subjects
- Adolescent, Adrenergic beta-Antagonists therapeutic use, Adult, Amiodarone administration & dosage, Amiodarone adverse effects, Andersen Syndrome genetics, Andersen Syndrome therapy, Anti-Arrhythmia Agents administration & dosage, Anti-Arrhythmia Agents adverse effects, Arrhythmias, Cardiac therapy, Child, Child, Preschool, Databases, Factual, Death, Sudden, Cardiac epidemiology, Defibrillators, Implantable, Electrocardiography, Female, Genetic Testing, Humans, Infant, Male, Middle Aged, Muscle Weakness etiology, Mutation, Potassium Channels, Inwardly Rectifying genetics, Syncope etiology, Syncope therapy, Tachycardia, Ventricular etiology, Tachycardia, Ventricular therapy, Young Adult, Andersen Syndrome complications, Arrhythmias, Cardiac etiology, Risk Assessment
- Abstract
Background: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported., Objectives: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1., Methods: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis., Results: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00)., Conclusions: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1., (Copyright © 2020. Published by Elsevier Inc.)
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- 2020
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33. Italian recommendations for the management of pediatric patients under twelve years of age with suspected or manifest Brugada syndrome.
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Drago F, Bloise R, Bronzetti G, Leoni L, Porcedda G, Sarubbi B, De Filippo P, Gulletta S, and Scaglione M
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- Brugada Syndrome complications, Brugada Syndrome physiopathology, Cardiology, Child, Child, Preschool, Death, Sudden, Cardiac etiology, Death, Sudden, Cardiac prevention & control, Defibrillators, Implantable, Electrocardiography, Female, Fever etiology, Genetic Testing, Humans, Infant, Infant, Newborn, Italy, Male, NAV1.5 Voltage-Gated Sodium Channel genetics, Risk Factors, Sex Factors, Societies, Medical, Sports, Brugada Syndrome diagnosis, Brugada Syndrome therapy
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- 2020
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34. Unexpected Risk Profile of a Large Pediatric Population With Brugada Syndrome.
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Mazzanti A, Ovics P, Shauer A, Mameli S, Marino M, Bloise R, Monteforte N, Raimondo C, Maltret A, Napolitano C, Bagnardi V, and Priori SG
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- Adolescent, Child, Electrocardiography methods, Female, Follow-Up Studies, Humans, Italy epidemiology, Male, Patient Selection, Risk Factors, Symptom Assessment methods, Symptom Assessment statistics & numerical data, Arrhythmias, Cardiac etiology, Arrhythmias, Cardiac therapy, Brugada Syndrome diagnosis, Brugada Syndrome epidemiology, Brugada Syndrome physiopathology, Brugada Syndrome therapy, Heart Arrest diagnosis, Heart Arrest prevention & control, Patient Care Management methods, Risk Assessment methods
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- 2019
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35. Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
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Mazzanti A, Maragna R, Vacanti G, Monteforte N, Bloise R, Marino M, Braghieri L, Gambelli P, Memmi M, Pagan E, Morini M, Malovini A, Ortiz M, Sacilotto L, Bellazzi R, Monserrat L, Napolitano C, Bagnardi V, and Priori SG
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- Cohort Studies, Female, Genotype, Humans, Long QT Syndrome genetics, Male, Risk Assessment, Heart physiopathology, Long QT Syndrome physiopathology
- Abstract
Background: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs)., Objectives: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS., Methods: Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers., Results: The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03)., Conclusions: The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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36. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome.
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Mazzanti A, Maragna R, Vacanti G, Kostopoulou A, Marino M, Monteforte N, Bloise R, Underwood K, Tibollo V, Pagan E, Napolitano C, Bellazzi R, Bagnardi V, and Priori SG
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- Adolescent, Adult, Anti-Arrhythmia Agents administration & dosage, Arrhythmias, Cardiac complications, Arrhythmias, Cardiac physiopathology, Death, Sudden, Cardiac epidemiology, Death, Sudden, Cardiac etiology, Electrocardiography, Female, Follow-Up Studies, Heart Conduction System drug effects, Heart Conduction System physiopathology, Heart Rate drug effects, Humans, Incidence, Italy epidemiology, Male, Quinidine administration & dosage, Survival Rate trends, Ventricular Fibrillation complications, Ventricular Fibrillation epidemiology, Young Adult, Arrhythmias, Cardiac drug therapy, Death, Sudden, Cardiac prevention & control, Quinidine analogs & derivatives, Ventricular Fibrillation prevention & control
- Abstract
Background: Short QT syndrome (SQTS) is a rare and life-threatening arrhythmogenic syndrome characterized by abbreviated repolarization. Hydroquinidine (HQ) prolongs the QT interval in SQTS patients, although whether it reduces cardiac events is currently unknown., Objectives: This study investigated whether long-term treatment with HQ reduces the occurrence of life-threatening arrhythmic events (LAE) (cardiac arrest or sudden cardiac death) in SQTS patients., Methods: In this cohort study on consecutive SQTS patients, 2 analyses were performed: 1) a matched-period analysis for the occurrence of LAE in 17 SQTS patients who received long-term HQ; and 2) a comparison of the annual incidence of LAE off- and on-HQ in 16 SQTS patients who survived a cardiac arrest., Results: A total of 17 patients (82% male, age 29 ± 3 years, QTc before treatment 331 ± 3 ms) received HQ therapy (584 ± 53 mg/day). Therapy was stopped in 2 cases (12%) due to gastrointestinal intolerance, and 15 patients continued treatment for 6 ± 1 year. QTc prolongation was observed in all patients (by 60 ± 6 ms; p < 0.001). We compared the occurrence of LAE during 6 ± 1 years before and after HQ, observing that patients on HQ experienced a reduction in both the rate of LAE from 40% to 0% (p = 0.03) and the number of LAE per patient from 0.73 ± 0.3 to 0 (p = 0.026). Furthermore, the annual rate of LAE in the 16 patients with a previous cardiac arrest dropped from 12% before HQ to 0 on therapy (p = 0.028)., Conclusions: We demonstrated for the first time that treatment with HQ was associated with a lower incidence of LAE in SQTS patients. These data point to the importance that quinidine, that in several countries has been removed from the market, remains available worldwide for patients with SQTS. In the present study, therapy with HQ has been proven to be safe, with a relatively low rate of side effects., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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37. Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk.
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Mazzanti A, Ng K, Faragli A, Maragna R, Chiodaroli E, Orphanou N, Monteforte N, Memmi M, Gambelli P, Novelli V, Bloise R, Catalano O, Moro G, Tibollo V, Morini M, Bellazzi R, Napolitano C, Bagnardi V, and Priori SG
- Subjects
- Adolescent, Adult, Arrhythmogenic Right Ventricular Dysplasia complications, Arrhythmogenic Right Ventricular Dysplasia epidemiology, Child, Child, Preschool, Death, Sudden, Cardiac epidemiology, Death, Sudden, Cardiac prevention & control, Defibrillators, Implantable, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Infant, Infant, Newborn, Italy epidemiology, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate trends, Time Factors, Young Adult, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Death, Sudden, Cardiac etiology, Risk Assessment methods
- Abstract
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined., Objectives: This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy., Methods: We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry. Predictors of LAE over 5.8 years of follow-up were determined with Cox multivariable analysis. Treatment efficacy was assessed comparing LAE rates during matched time intervals., Results: A first LAE occurred in 1.5 per 100 person-years between birth and age 20 years, in 4.0 per 100 person-years between ages 21 and 40 years, and in 2.4 per 100 person-years between ages 41 and 60 years. Cumulative probability of a first LAE at follow-up was 14% at 5 years, 23% at 10 years, and 30% at 15 years. Higher risk of LAE was predicted by atrial fibrillation (hazard ratio [HR]: 4.38; p = 0.002), syncope (HR: 3.36; p < 0.001), participation in strenuous exercise after the diagnosis (HR: 2.98; p = 0.028), hemodynamically tolerated sustained monomorphic ventricular tachycardia (HR: 2.19; p = 0.023), and male sex (HR: 2.49; p = 0.012). No difference was observed in the occurrence of LAE before and after treatment with amiodarone, beta-blockers, sotalol, or ablation. A total of 81 patients received an implantable cardioverter-defibrillator, 34 were successfully defibrillated., Conclusions: The high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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38. Clinical Presentation and Outcome of Brugada Syndrome Diagnosed With the New 2013 Criteria.
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Curcio A, Mazzanti A, Bloise R, Monteforte N, Indolfi C, Priori SG, and Napolitano C
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- Action Potentials, Adult, Brugada Syndrome physiopathology, Brugada Syndrome therapy, Female, Heart Rate, Humans, Male, Middle Aged, Practice Guidelines as Topic, Predictive Value of Tests, Prognosis, Registries, Young Adult, Brugada Syndrome diagnosis, Electrocardiography standards, Heart Conduction System physiopathology
- Abstract
Introduction: The 2013 HRS/EHRA/APHRS consensus statement recommends the use of V1 and V2 leads recorded in the second and third intercostal spaces (High-ICS) for diagnosis of Brugada syndrome (BrS) creating a new category of patients discovered only with modified leads. The clinical presentation and the arrhythmic risk in these patients are ill defined. This study was aimed at assessing the role of High-ICS in the analysis of BrS and the clinical profile of the patients diagnosed only when ECG leads are moved to upper intercostal spaces., Methods and Results: We searched our Brugada syndrome registry and identified 300 subjects (age 36 ± 13 years), without a diagnostic coved ST-segment elevation in conventional V1 -V3 leads, both at baseline and after provocative drug challenge. Sixty-four subjects (21.3%, mean age at last follow-up 42 ± 11 years) were diagnosed with High-ICS. Diagnosis was possible at baseline only in 4 subjects while in 60 it was made after drug challenge with sodium channel blockers. Three subjects (4.7%) with spontaneous abnormal ECG experienced cardiac events with an annual event rate (0.11%) superimposable to that of the low risk category of BrS diagnosed in standard leads., Conclusion: This study demonstrates that the use of new diagnostic criteria for BrS allows increasing the diagnostic yield by 20% and that the arrhythmic risk is low when BrS can be established only in High-ICS. We also show that the prognostic value of spontaneous ECG pattern is confirmed in this subgroup., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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39. Dysgeusia #304.
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Bloise R and Davis MP
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- Dysgeusia diagnosis, Dysgeusia etiology, Humans, Quality of Life, Dysgeusia therapy, Palliative Care
- Published
- 2016
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40. Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3.
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Mazzanti A, Maragna R, Faragli A, Monteforte N, Bloise R, Memmi M, Novelli V, Baiardi P, Bagnardi V, Etheridge SP, Napolitano C, and Priori SG
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- Administration, Oral, Adolescent, Adult, Child, Female, Follow-Up Studies, Humans, Long QT Syndrome genetics, Long QT Syndrome physiopathology, Male, Retrospective Studies, Treatment Outcome, Voltage-Gated Sodium Channel Blockers administration & dosage, Young Adult, Electrocardiography, Genetic Therapy methods, Heart Rate drug effects, Long QT Syndrome therapy, Mexiletine administration & dosage
- Abstract
Background: Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients., Objectives: The aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients., Methods: The endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine., Results: The study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097)., Conclusions: Besides shortening QTc interval, mexiletine caused a major reduction of life-threatening arrhythmic events in LQT3 patients, thus representing an efficacious therapeutic strategy., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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41. Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1.
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Corona-Rivera JR, Barrios-Prieto E, Nieto-García R, Bloise R, Priori S, Napolitano C, Bobadilla-Morales L, Corona-Rivera A, Zapata-Aldana E, Peña-Padilla C, Rivera-Vargas J, and Chavana-Naranjo E
- Subjects
- Adrenergic Uptake Inhibitors adverse effects, Amitriptyline adverse effects, Autistic Disorder genetics, Female, Fetal Heart diagnostic imaging, Fetal Heart drug effects, Humans, Infant, Newborn, Long QT Syndrome genetics, Male, Mutation, Missense, Pregnancy, Syndactyly genetics, Ultrasonography, Prenatal, Autistic Disorder diagnosis, Calcium Channels, L-Type genetics, Long QT Syndrome diagnosis, Syndactyly diagnosis
- Abstract
Timothy syndrome 1 (TS1) is a multisystem disorder characterized by severe QT prolongation and potentially lethal ventricular arrhythmias in the first years of life, plus other cardiac and extracardiac manifestations caused by mutation in the CACNA1C gene, a CaV1.2 L-type calcium channel. Here, we report retrospectively an unusual fetal presentation on a second patient with TS1 with fetal hydrops due to a congenital AV block and its postnatal diagnosis by a marked prolongation of the corrected QTc interval of 570 ms and a missense mutation, p.Gly406Arg, in exon 8A of CACNA1C gene. The observed manifestations in our patient during fetal period indicate a severe form and they were probably exacerbated by the maternal use of amitriptyline during the first 4 months of pregnancy. Unfortunately, he died at 3 months-old due a ventricular tachycardia and fibrillation related to a septic event. Although difficult to diagnose, possibly most fetuses with TS1 have symptoms of long QT syndrome. Despite the fatal outcome for our patient, an early diagnosis of TS may help to prevent life-threatening events or early death in future patients, especially in developing countries where availability of therapies such as cardioverter defibrillator are very limited, or require time for its funding., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
- Published
- 2015
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42. Efficacy and safety of a six-hour continuous overlap method for converting intravenous to transdermal fentanyl in cancer pain.
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Samala RV, Bloise R, and Davis MP
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- Administration, Cutaneous, Administration, Intravenous, Adult, Aged, Aged, 80 and over, Analgesics, Opioid adverse effects, Female, Fentanyl adverse effects, Humans, Male, Middle Aged, Neoplasm Staging, Pain Management methods, Pain Measurement, Palliative Care methods, Time Factors, Analgesics, Opioid administration & dosage, Fentanyl administration & dosage, Neoplasms physiopathology, Pain drug therapy, Pain physiopathology
- Abstract
Context: Managing cancer pain often requires opioid medications, such as fentanyl, which is frequently initiated parenterally, and then converted to transdermal form. Little evidence exists to guide this conversion., Objectives: To observe the efficacy and safety of a six-hour continuous overlap method for converting intravenous fentanyl (IVF) to transdermal fentanyl (TF) in patients with cancer pain., Methods: We switched from IVF to TF using a 1:1 (IVF:TF) conversion ratio and overlapped a continuous, nontapered dose of IVF until six hours after TF placement. Pain intensity by Numeric Rating Scale, number of rescue analgesic doses, and presence and severity of opioid-related adverse events were recorded immediately before TF placement, and at six, 12, 18, and 24 hours thereafter., Results: A total of 17 consecutive patients with cancer pain controlled on IVF were converted to TF. Median age was 65 years, 10 were female, and all had Stage IV cancer. Pain intensity at six and 24 hours remained stable; a slight but statistically significant increase in Numeric Rating Scale was noted at 12 and 18 hours (P=0.01 and 0.02, respectively); however, there was no significant increase in number of rescue doses throughout the observation period. Only one patient experienced opioid-related adverse events., Conclusion: A continuous six-hour overlap method is a safe and effective strategy when converting from IVF to TF in patients with cancer pain. A slight increase in pain intensity may occur, but does not lead to increased rescue doses., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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43. Novel insight into the natural history of short QT syndrome.
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Mazzanti A, Kanthan A, Monteforte N, Memmi M, Bloise R, Novelli V, Miceli C, O'Rourke S, Borio G, Zienciuk-Krajka A, Curcio A, Surducan AE, Colombo M, Napolitano C, and Priori SG
- Subjects
- Adult, Arrhythmias, Cardiac epidemiology, Arrhythmias, Cardiac genetics, Arrhythmias, Cardiac metabolism, DNA Mutational Analysis, Ether-A-Go-Go Potassium Channels metabolism, Female, Follow-Up Studies, Gene Frequency, Humans, Incidence, Italy epidemiology, Male, Survival Rate trends, Time Factors, Young Adult, DNA genetics, Electrocardiography, Ether-A-Go-Go Potassium Channels genetics, Genetic Predisposition to Disease, Genetic Testing methods, Mutation
- Abstract
Objectives: This study intends to gain further insights into the natural history, the yield of familial and genetic screening, and the arrhythmogenic mechanisms in the largest cohort of short QT syndrome (SQTS) patients described so far., Background: SQTS is a rare genetic disorder associated with life-threatening arrhythmias, and its natural history is incompletely ascertained., Methods: Seventy-three SQTS patients (84% male; age, 26 ± 15 years; corrected QT interval, 329 ± 22 ms) were studied, and 62 were followed for 60 ± 41 months (median, 56 months)., Results: Cardiac arrest (CA) was the most frequent presenting symptom (40% of probands; range, <1 month to 41 years). The rate of CA was 4% in the first year of life and 1.3% per year between 20 and 40 years; the probability of a first occurrence of CA by 40 years of age was 41%. Despite the male predominance, female patients had a risk profile superimposable to that of men (p = 0.49). The yield of genetic screening was low (14%), despite familial disease being present in 44% of kindreds. A history of CA was the only predictor of recurrences at follow-up (p < 0.0000001). Two patterns of onset of ventricular fibrillation were observed and were reproducible in patients with multiple occurrences of CA. Arrhythmias occurred mainly at rest., Conclusions: SQTS is highly lethal; CA is often the first manifestation of the disease with a peak incidence in the first year of life. Survivors of CA have a high CA recurrence rate; therefore, implantation of a defibrillator is strongly recommended in this group of patients., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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44. Clinical utility gene card for: Catecholaminergic polymorphic ventricular tachycardia (CPVT).
- Author
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Napolitano C, Bloise R, Memmi M, and Priori SG
- Subjects
- Humans, Mutation, Tachycardia, Ventricular diagnosis, Tachycardia, Ventricular therapy, Calsequestrin genetics, Ryanodine Receptor Calcium Release Channel genetics, Tachycardia, Ventricular genetics
- Published
- 2014
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- View/download PDF
45. KSHV ORF67 encoded lytic protein localizes on the nuclear membrane and alters emerin distribution.
- Author
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Farina A, Santarelli R, Bloise R, Gonnella R, Granato M, Bei R, Modesti A, Cirone M, Bengtsson L, Angeloni A, and Faggioni A
- Subjects
- Cell Line, Humans, Herpesvirus 8, Human physiology, Host-Pathogen Interactions, Membrane Proteins metabolism, Nuclear Envelope chemistry, Nuclear Proteins metabolism, Viral Proteins metabolism, Virus Replication
- Abstract
p29, a newly identified Kaposi's sarcoma-associated herpesvirus (KSHV) protein, is the product of ORF67, the positional homolog of the conserved herpesvirus protein UL34. Like its homologues in other herpesviruses, p29 is expressed early during viral lytic cycle, and is localized on the nuclear rim. Upon chemical induction of viral replication in primary effusion lymphoma cells, p29 interacts with p33, encoded by ORF69, the positional homolog of the conserved herpesvirus protein UL31, and both proteins colocalize on the nuclear membrane. IFA and biochemical analysis of infected or transfected cells showed that p29 expression resulted in delocalization and hyperphosphorylation of emerin, whereas other nuclear lamin associated proteins, such as LUMA, LB1 and LBR were not affected. Mislocalization of emerin was robustly increased upon combined expression of p29 and p33, suggesting that emerin destabilization might represent the first step in nuclear lamina disassembling, a process necessary for nucleocapsid maturation., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
46. 19q13 microdeletion syndrome: Further refining the critical region.
- Author
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Forzano F, Napoli F, Uliana V, Malacarne M, Viaggi C, Bloise R, Coviello D, Di Maria E, Olivieri I, Di Iorgi N, and Faravelli F
- Subjects
- Abnormalities, Multiple genetics, Child, Chromosomes, Human, Pair 18 genetics, Chromosomes, Human, Pair 8 genetics, Comparative Genomic Hybridization, Female, Genetic Association Studies, Humans, Syndrome, Abnormalities, Multiple diagnosis, Chromosome Deletion, Chromosomes, Human, Pair 19 genetics
- Abstract
The 19q13 microdeletion syndrome is a recently identified disorder of which very few cases have been reported so far. Growth deficiency, microcephaly, ectodermal anomalies and intellectual disability are the major features reported in all the described cases. The critical region has been estimated to span 750 Kb. We report an Italian patient carrying a de novo 1.37 Mb deletion in chromosome 19q13, who presented all the cardinal features of the syndrome, and multiple pituitary hormone deficiency. Our findings might contribute to further refine the critical region to 460 Kb and restrict the list of candidate genes., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
- Published
- 2012
- Full Text
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47. Genetic Testing for Cardiac Arrhythmias: Ready for Prime Time?
- Author
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Fowler SJ and Bloise R
- Abstract
Despite the heterogeneity of substrates and clinical expressivity, genetic testing has a direct impact on clinical practice: it allows a specific diagnosis, including silent carriers (ie, asymptomatic diagnosis) and, in select diseases, the identification of a mutation has major impact for risk stratification and treatment of patients. This article addresses the role of genetic testing for each of the most epidemiologically relevant inherited arrhythmogenic diseases, specifically long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy., (Copyright © 2010. Published by Elsevier Inc.)
- Published
- 2010
- Full Text
- View/download PDF
48. Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QT syndrome.
- Author
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Tomás M, Napolitano C, De Giuli L, Bloise R, Subirana I, Malovini A, Bellazzi R, Arking DE, Marban E, Chakravarti A, Spooner PM, and Priori SG
- Subjects
- Adult, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Incidence, Long QT Syndrome epidemiology, Long QT Syndrome physiopathology, Male, Polymerase Chain Reaction, Prognosis, Prospective Studies, Risk Factors, Time Factors, Adaptor Proteins, Signal Transducing genetics, DNA genetics, Electrocardiography, Long QT Syndrome genetics, Polymorphism, Genetic
- Abstract
Objectives: We investigated the role of nitric oxide 1 adaptor protein (NOS1AP) as a genetic modifier of long QT syndrome (LQTS)., Background: LQTS risk stratification is complicated by the phenotype variability that limits prediction of life-threatening arrhythmic events based on available metrics. Thus, the identification of new markers is desirable. Recent studies have shown that NOS1AP variations in the gene modulate QT interval in healthy and 1 LQTS kindred, and occurrence of cardiac events in healthy subjects., Methods: The study included 901 patients enrolled in a prospective LQTS registry. Three NOS1AP marker SNPs (rs4657139, rs16847548, and rs10494366) were genotyped to assess the effect of variant alleles on QTc and on the incidence of cardiac events. We quantified the association between variant alleles, QTc, and outcomes to assess whether NOS1AP is a useful risk stratifier in LQTS., Results: Variant alleles tagged by SNPs rs4657139 and rs16847548 were associated with an average QTc prolongation of 7 and 8 ms, respectively (p < 0.05; p < 0.01); whereas rs4657139 and rs10494366 were associated with increased incidence of cardiac events (25.2% vs. 18.0%, p < 0.05 and 24.8% vs. 17.8% p < 0.05). Cox multivariate analysis identified rs10494366 minor allele as an independent prognostic marker among patients with QTc <500 ms (hazard ratio: 1.63; 95% confidence interval: 1.06 to 2.5; p < 0.05) but not in the entire cohort., Conclusions: Our results provide the first demonstration, to our knowledge, of a risk-conferring genetic modifier in a large LQTS cohort. Subject to confirmation in additional cohorts, we suggest that the NOS1AP tag SNP genotype may provide an additional clinical dimension, which helps assess risk and choice of therapeutic strategies in LQTS., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
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49. Charcot-Marie-Tooth type 1a in a child with Long QT syndrome.
- Author
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Losito L, De Rinaldis M, Gennaro L, Priori SG, Bloise R, Bassi MT, Bresolin N, and Trabacca A
- Subjects
- Adult, Child, Chromosome Disorders genetics, DNA Mutational Analysis, Electrocardiography, Ambulatory, Electrophysiology, Female, Gene Duplication, Humans, Male, Pedigree, Young Adult, Charcot-Marie-Tooth Disease complications, Charcot-Marie-Tooth Disease genetics, Long QT Syndrome complications, Long QT Syndrome genetics
- Abstract
Charcot-Marie-Tooth disease (CMTD) is a hereditary demyelinating peripheral neuropathy clinically presenting with sensory and motor defects, but rarely affecting cardiac function. Long QT syndrome (LQTS) is a congenital or acquired cardiovascular disorder characterized by ventricular depolarization defect. No studies reported CMTD in association with LQTS. We describe a child and his family who had both CMT1A and LQTS.
- Published
- 2009
- Full Text
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50. Magnetic resonance investigations in Brugada syndrome reveal unexpectedly high rate of structural abnormalities.
- Author
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Catalano O, Antonaci S, Moro G, Mussida M, Frascaroli M, Baldi M, Cobelli F, Baiardi P, Nastoli J, Bloise R, Monteforte N, Napolitano C, and Priori SG
- Subjects
- Adolescent, Adult, Aged, Brugada Syndrome physiopathology, Case-Control Studies, Death, Sudden, Cardiac pathology, Female, Heart Ventricles pathology, Humans, Magnetic Resonance Angiography, Male, Middle Aged, Myocardial Contraction physiology, Stroke Volume physiology, Young Adult, Brugada Syndrome pathology
- Abstract
Aims: Recent data suggest that sub-clinical structural abnormalities may be part of the Brugada syndrome (BrS) phenotype, a disease traditionally thought to occur in the structurally normal heart. In this study, we carried out detailed assessment of cardiac morphology and function using cardiac magnetic resonance imaging (CMRI)., Methods and Results: Thirty consecutive patients with BrS were compared with 30 sex- (26/4 male/female), body surface area- (+/-0.2 m(2)), and age-matched (+/-5 years) normal volunteers. CMRI exam included long- and short-axis ECG-gated breath-hold morphological T1-TSE sequences for fatty infiltration and cine-SSFP sequences for kinetic assessment. Fatty infiltration was not found in any subject. Patients with BrS compared with normal subjects showed higher incidence of mild right ventricle (RV) wall-motion abnormalities [15 (50%) vs. 5 (17%) subjects (P = 0.006) with reduced radial fractional shortening in more than two segments], reduction of outflow tract ejection fraction (49 +/- 11% vs. 55 +/- 10%; P = 0.032), enlargement of the inflow tract diameter (46 +/- 4 vs. 41 +/- 5 mm, P < 0.001 in short-axis; 46 +/- 4 vs. 42 +/- 5 mm, P = 0.001 in four-chamber long-axis view) and area (22 +/- 2 vs. 20 +/- 3 cm(2); P = 0.050), and of global RV end-systolic volume (34 +/- 10 vs. 30 +/- 6 mL/m(2); P = 0.031) but comparable outflow tract dimensions, global RV end-diastolic volume, left ventricle parameters, and atria areas., Conclusion: CMRI detects a high prevalence of mild structural changes of the RV, and suggests further pathophysiological complexity in BrS. Prospective studies to assess the long-term evolution of such abnormalities are warranted.
- Published
- 2009
- Full Text
- View/download PDF
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