52 results on '"Kukavica D"'
Search Results
2. Artificial intelligence-driven echocardiographic classification identifies Brugada Syndrome patients at higher arrhythmic risk
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Kukavica, D, primary, Trancuccio, A, additional, Esposito, A, additional, Marino, M, additional, Bloise, R, additional, Napolitano, C, additional, Mazzanti, A, additional, and Priori, S G, additional
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- 2023
- Full Text
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3. Overexpression of cardiac calsequestrin as a novel gene-therapy approach to treat CPVT1: in silico and in vivo proves of principle
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Santiago Castillo, D, primary, Bongianino, R, additional, Trancuccio, A, additional, Kukavica, D, additional, Tarifa, C, additional, Denegri, M, additional, Mazzanti, A, additional, and Priori, S G, additional
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- 2023
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4. Unexpectedly high prevalence of structural genomic variations in the Long QT Syndrome: evidence for broader clinical uptake
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Mazzanti, A, primary, Memmi, M, additional, Gambelli, P, additional, Guarracino, A, additional, Colombi, B, additional, Nastoli, J, additional, Trancuccio, A, additional, Kukavica, D, additional, Marino, M, additional, Bloise, R, additional, Napolitano, C, additional, and Priori, S G, additional
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- 2023
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5. Acute Myocarditis Associated With Desmosomal Gene Variants
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Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, S, Mazzanti, A, Shenoy, C, Cavallari, U, Imazio, M, Aquaro, G, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, C, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, R, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, C, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, G, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, J, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, J, Bernasconi, D, Valsecchi, M, Klingel, K, Adler, E, Camici, P, Cooper, L, Ammirati E., Raimondi F., Piriou N., Sardo Infirri L., Mohiddin S. A., Mazzanti A., Shenoy C., Cavallari U. A., Imazio M., Aquaro G. D., Olivotto I., Pedrotti P., Sekhri N., Van de Heyning C. M., Broeckx G., Peretto G., Guttmann O., Dellegrottaglie S., Scatteia A., Gentile P., Merlo M., Goldberg R. I., Reyentovich A., Sciamanna C., Klaassen S., Poller W., Trankle C. R., Abbate A., Keren A., Horowitz-Cederboim S., Cadrin-Tourigny J., Tadros R., Annoni G. A., Bonoldi E., Toquet C., Marteau L., Probst V., Trochu J. N., Kissopoulou A., Grosu A., Kukavica D., Trancuccio A., Gil C., Tini G., Pedrazzini M., Torchio M., Sinagra G., Gimeno J. R., Bernasconi D., Valsecchi M. G., Klingel K., Adler E. D., Camici P. G., Cooper L. T., Ammirati, E, Raimondi, F, Piriou, N, Sardo Infirri, L, Mohiddin, S, Mazzanti, A, Shenoy, C, Cavallari, U, Imazio, M, Aquaro, G, Olivotto, I, Pedrotti, P, Sekhri, N, Van de Heyning, C, Broeckx, G, Peretto, G, Guttmann, O, Dellegrottaglie, S, Scatteia, A, Gentile, P, Merlo, M, Goldberg, R, Reyentovich, A, Sciamanna, C, Klaassen, S, Poller, W, Trankle, C, Abbate, A, Keren, A, Horowitz-Cederboim, S, Cadrin-Tourigny, J, Tadros, R, Annoni, G, Bonoldi, E, Toquet, C, Marteau, L, Probst, V, Trochu, J, Kissopoulou, A, Grosu, A, Kukavica, D, Trancuccio, A, Gil, C, Tini, G, Pedrazzini, M, Torchio, M, Sinagra, G, Gimeno, J, Bernasconi, D, Valsecchi, M, Klingel, K, Adler, E, Camici, P, Cooper, L, Ammirati E., Raimondi F., Piriou N., Sardo Infirri L., Mohiddin S. A., Mazzanti A., Shenoy C., Cavallari U. A., Imazio M., Aquaro G. D., Olivotto I., Pedrotti P., Sekhri N., Van de Heyning C. M., Broeckx G., Peretto G., Guttmann O., Dellegrottaglie S., Scatteia A., Gentile P., Merlo M., Goldberg R. I., Reyentovich A., Sciamanna C., Klaassen S., Poller W., Trankle C. R., Abbate A., Keren A., Horowitz-Cederboim S., Cadrin-Tourigny J., Tadros R., Annoni G. A., Bonoldi E., Toquet C., Marteau L., Probst V., Trochu J. N., Kissopoulou A., Grosu A., Kukavica D., Trancuccio A., Gil C., Tini G., Pedrazzini M., Torchio M., Sinagra G., Gimeno J. R., Bernasconi D., Valsecchi M. G., Klingel K., Adler E. D., Camici P. G., and Cooper L. T.
- Abstract
Background: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. Objectives: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. Methods: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[−]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. Results: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(−) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. Conclusions: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.
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- 2022
6. Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk): comment - Authors' reply
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Mazzanti, A, Trancuccio, A, Kukavica, D, Pagan, E, Wang, M, Mohsin, M, Peterson, D, Bagnardi, V, Zareba, W, Priori, S, Mazzanti A., Trancuccio A., Kukavica D., Pagan E., Wang M., Mohsin M., Peterson D., Bagnardi V., Zareba W., Priori S. G., Mazzanti, A, Trancuccio, A, Kukavica, D, Pagan, E, Wang, M, Mohsin, M, Peterson, D, Bagnardi, V, Zareba, W, Priori, S, Mazzanti A., Trancuccio A., Kukavica D., Pagan E., Wang M., Mohsin M., Peterson D., Bagnardi V., Zareba W., and Priori S. G.
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- 2022
7. Value of 3D echocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy
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Addetia, K, Mazzanti, A, Maragna, R, Monti, L, Yamat, M, Kukavica, D, Pagan, E, Kishiki, K, Prado, A, Marino, M, Bagnardi, V, Priori, S, Lang, R, Addetia, Karima, Mazzanti, Andrea, Maragna, Riccardo, Monti, Lorenzo, Yamat, Megan, Kukavica, Deni, Pagan, Eleonora, Kishiki, Kanako, Prado, Aldo, Marino, Maira, Bagnardi, Vincenzo, Priori, Silvia, Lang, Roberto M, Addetia, K, Mazzanti, A, Maragna, R, Monti, L, Yamat, M, Kukavica, D, Pagan, E, Kishiki, K, Prado, A, Marino, M, Bagnardi, V, Priori, S, Lang, R, Addetia, Karima, Mazzanti, Andrea, Maragna, Riccardo, Monti, Lorenzo, Yamat, Megan, Kukavica, Deni, Pagan, Eleonora, Kishiki, Kanako, Prado, Aldo, Marino, Maira, Bagnardi, Vincenzo, Priori, Silvia, and Lang, Roberto M
- Abstract
AIMS: The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC. METHODS AND RESULTS: Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE-cMRI and 2DE-3DE approaches. Using the 2DE-cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE-3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44-0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage. CONCLUSION: The combination of 2DE-3DE for ARVC diagnosis is comparable to the conventional 2DE-cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA.
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- 2023
8. Efficacy and safety of the ICD in patients with catecholaminergic polymorphic ventricular tachycardia
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Mazzanti, A, primary, Trancuccio, A, additional, Kukavica, D, additional, Marino, M, additional, Giannini, G, additional, Rossetti, L, additional, Memmi, M, additional, Bloise, R, additional, Morini, M, additional, Napolitano, C, additional, and Priori, S G, additional
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- 2022
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9. Catecholaminergic polymorphic ventricular tachycardia: risk modulators in patients treated with beta-blockers
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Kukavica, D, primary, Mazzanti, A, additional, Trancuccio, A, additional, Giannini, G, additional, Marino, M, additional, Memmi, M, additional, Gambelli, P, additional, Bloise, R, additional, Morini, M, additional, Ortiz-Genga, M, additional, Napolitano, C, additional, and Priori, S G, additional
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- 2022
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10. Natural History of Patients with Typical and Atypical Catecholaminergic Polymorphic Ventricular Tachycardia
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Trancuccio, A, primary, Mazzanti, A, additional, Kukavica, D, additional, Giannini, G, additional, Memmi, M, additional, Gambelli, P, additional, Bloise, R, additional, Marino, M, additional, Morini, M, additional, Ortiz-Genga, M, additional, Napolitano, C, additional, and Priori, S G, additional
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- 2022
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11. The COVID19 pandemic may lead to the activation of the forgotten tuberculosis
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Cvetković, M, primary, Kovačević, D, additional, Ilić, M, additional, Kukavica, D, additional, Savić, N, additional, Milenković, A, additional, and Javorac, J, additional
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- 2022
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12. Additional diagnostic value of cardiac magnetic resonance feature tracking in patients with biopsy-proven arrhythmogenic cardiomyopathy
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Muscogiuri, G, Fusini, L, Ricci, F, Sicuso, R, Guglielmo, M, Baggiano, A, Gasperetti, A, Casella, M, Mushtaq, S, Conte, E, Annoni, A, Formenti, A, Mancini, M, Babbaro, M, Mollace, R, Collevecchio, A, Scafuri, S, Kukavica, D, Andreini, D, Basso, C, Rizzo, S, De Gaspari, M, Priori, S, Dello Russo, A, Tondo, C, Pepi, M, Sommariva, E, Rabbat, M, Guaricci, A, Pontone, G, Muscogiuri G., Fusini L., Ricci F., Sicuso R., Guglielmo M., Baggiano A., Gasperetti A., Casella M., Mushtaq S., Conte E., Annoni A., Formenti A., Mancini M. E., Babbaro M., Mollace R., Collevecchio A., Scafuri S., Kukavica D., Andreini D., Basso C., Rizzo S., De Gaspari M., Priori S., Dello Russo A., Tondo C., Pepi M., Sommariva E., Rabbat M., Guaricci A. I., Pontone G., Muscogiuri, G, Fusini, L, Ricci, F, Sicuso, R, Guglielmo, M, Baggiano, A, Gasperetti, A, Casella, M, Mushtaq, S, Conte, E, Annoni, A, Formenti, A, Mancini, M, Babbaro, M, Mollace, R, Collevecchio, A, Scafuri, S, Kukavica, D, Andreini, D, Basso, C, Rizzo, S, De Gaspari, M, Priori, S, Dello Russo, A, Tondo, C, Pepi, M, Sommariva, E, Rabbat, M, Guaricci, A, Pontone, G, Muscogiuri G., Fusini L., Ricci F., Sicuso R., Guglielmo M., Baggiano A., Gasperetti A., Casella M., Mushtaq S., Conte E., Annoni A., Formenti A., Mancini M. E., Babbaro M., Mollace R., Collevecchio A., Scafuri S., Kukavica D., Andreini D., Basso C., Rizzo S., De Gaspari M., Priori S., Dello Russo A., Tondo C., Pepi M., Sommariva E., Rabbat M., Guaricci A. I., and Pontone G.
- Abstract
Background: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved. Methods: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF<55%) and compared to an age and gender-matched control group. CMR datasets of all patients were analyzed to calculate LV indexed end-diastolic (LVEDi) and end-systolic (LVESi) volumes and RV indexed end-diastolic (RVEDi) and end-systolic (RVESi) volumes, both LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Moreover, LV and RV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were measured. Results: The AC patients showed both higher LVEDi (p:0.002) and RVEDi (p:0.017) and lower LVEF (p: 0.016) as compared to control patients. Moreover, AC patients showed impaired LV-GLS (p < 0.001), LV-GRS (p < 0.001), LV-GCS (p < 0.001) and RV-GRS (p:0.026) as compared to control subjects. Group1 patients showed a significant reduction of LV-GRS (p < 0.05) and LV-GCS p < 0.01) as compared to control subjects. At univariate analysis LV-GCS was the most discriminatory parameter between Group1 vs heathy subjects with an optimal cut-off of −15.8 (Sensitivity: 74%; Specificity: 10%). Conclusions: In patients with AC biopsy-proven, CMR-FT could improve the diagnostic yield in the subset of patients who results negative for imaging TFC criteria resulting as useful gatekeeper for indication of myocardial biopsy in case of equivocal clinical and imaging presentation.
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- 2021
13. Arrhythmic Mitral Valve Prolapse: Introducing an Era of Multimodality Imaging-Based Diagnosis and Risk Stratification
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Kukavica, D, Guglielmo, M, Baggiano, A, Muscogiuri, G, Fusini, L, Muratori, M, Tamborini, G, Mantegazza, V, Trancuccio, A, Arnò, C, Mazzanti, A, Pepi, M, Priori, S, Pontone, G, Kukavica D, Guglielmo M, Baggiano A, Muscogiuri G, Fusini L, Muratori M, Tamborini G, Mantegazza V, Trancuccio A, Arnò C, Mazzanti A, Pepi M, Priori SG, Pontone G, Kukavica, D, Guglielmo, M, Baggiano, A, Muscogiuri, G, Fusini, L, Muratori, M, Tamborini, G, Mantegazza, V, Trancuccio, A, Arnò, C, Mazzanti, A, Pepi, M, Priori, S, Pontone, G, Kukavica D, Guglielmo M, Baggiano A, Muscogiuri G, Fusini L, Muratori M, Tamborini G, Mantegazza V, Trancuccio A, Arnò C, Mazzanti A, Pepi M, Priori SG, and Pontone G
- Abstract
Mitral valve prolapse is a common cardiac condition, with an estimated prevalence between 1% and 3%. Most patients have a benign course, but ever since its initial description mitral valve prolapse has been associated to sudden cardiac death. Although the causal relationship between mitral valve prolapse and sudden cardiac death has never been clearly demonstrated, different factors have been implicated in arrhythmogenesis in patients with mitral valve prolapse. In this work, we offer a comprehensive overview of the etiology and the genetic background, epidemiology, pathophysiology, and we focus on the state-of-the-art imaging-based diagnosis of mitral valve prolapse. Going beyond the classical, well-described clinical factors, such as young age, female gender and auscultatory findings, we investigate multimodality imaging features, such as alterations of anatomy and function of the mitral valve and its leaflets, the structural and contractile anomalies of the myocardium, all of which have been associated to sudden cardiac death.
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- 2021
14. An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition
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Roberts, J, Asaki, S, Mazzanti, A, Bos, J, Tuleta, I, Muir, A, Crotti, L, Krahn, A, Kutyifa, V, Shoemaker, M, Johnsrude, C, Aiba, T, Marcondes, L, Baban, A, Udupa, S, Dechert, B, Fischbach, P, Knight, L, Vittinghoff, E, Kukavica, D, Stallmeyer, B, Giudicessi, J, Spazzolini, C, Shimamoto, K, Tadros, R, Cadrin-Tourigny, J, Duff, H, Simpson, C, Roston, T, Wijeyeratne, Y, El Hajjaji, I, Yousif, M, Gula, L, Leong-Sit, P, Chavali, N, Landstrom, A, Marcus, G, Dittmann, S, Wilde, A, Behr, E, Tfelt-Hansen, J, Scheinman, M, Perez, M, Kaski, J, Gow, R, Drago, F, Aziz, P, Abrams, D, Gollob, M, Skinner, J, Shimizu, W, Kaufman, E, Roden, D, Zareba, W, Schwartz, P, Schulze-Bahr, E, Etheridge, S, Priori, S, Ackerman, M, Roberts JD, Asaki SY, Mazzanti A, Bos JM, Tuleta I, Muir AR, Crotti L, Krahn AD, Kutyifa V, Shoemaker MB, Johnsrude CL, Aiba T, Marcondes L, Baban A, Udupa S, Dechert B, Fischbach P, Knight LM, Vittinghoff E, Kukavica D, Stallmeyer B, Giudicessi JR, Spazzolini C, Shimamoto K, Tadros R, Cadrin-Tourigny J, Duff HJ, Simpson CS, Roston TM, Wijeyeratne YD, El Hajjaji I, Yousif MD, Gula LJ, Leong-Sit P, Chavali N, Landstrom AP, Marcus GM, Dittmann S, Wilde AAM, Behr ER, Tfelt-Hansen J, Scheinman MM, Perez MV, Kaski JP, Gow RM, Drago F, Aziz PF, Abrams DJ, Gollob MH, Skinner JR, Shimizu W, Kaufman ES, Roden DM, Zareba W, Schwartz PJ, Schulze-Bahr E, Etheridge SP, Priori SG, Ackerman MJ., Roberts, J, Asaki, S, Mazzanti, A, Bos, J, Tuleta, I, Muir, A, Crotti, L, Krahn, A, Kutyifa, V, Shoemaker, M, Johnsrude, C, Aiba, T, Marcondes, L, Baban, A, Udupa, S, Dechert, B, Fischbach, P, Knight, L, Vittinghoff, E, Kukavica, D, Stallmeyer, B, Giudicessi, J, Spazzolini, C, Shimamoto, K, Tadros, R, Cadrin-Tourigny, J, Duff, H, Simpson, C, Roston, T, Wijeyeratne, Y, El Hajjaji, I, Yousif, M, Gula, L, Leong-Sit, P, Chavali, N, Landstrom, A, Marcus, G, Dittmann, S, Wilde, A, Behr, E, Tfelt-Hansen, J, Scheinman, M, Perez, M, Kaski, J, Gow, R, Drago, F, Aziz, P, Abrams, D, Gollob, M, Skinner, J, Shimizu, W, Kaufman, E, Roden, D, Zareba, W, Schwartz, P, Schulze-Bahr, E, Etheridge, S, Priori, S, Ackerman, M, Roberts JD, Asaki SY, Mazzanti A, Bos JM, Tuleta I, Muir AR, Crotti L, Krahn AD, Kutyifa V, Shoemaker MB, Johnsrude CL, Aiba T, Marcondes L, Baban A, Udupa S, Dechert B, Fischbach P, Knight LM, Vittinghoff E, Kukavica D, Stallmeyer B, Giudicessi JR, Spazzolini C, Shimamoto K, Tadros R, Cadrin-Tourigny J, Duff HJ, Simpson CS, Roston TM, Wijeyeratne YD, El Hajjaji I, Yousif MD, Gula LJ, Leong-Sit P, Chavali N, Landstrom AP, Marcus GM, Dittmann S, Wilde AAM, Behr ER, Tfelt-Hansen J, Scheinman MM, Perez MV, Kaski JP, Gow RM, Drago F, Aziz PF, Abrams DJ, Gollob MH, Skinner JR, Shimizu W, Kaufman ES, Roden DM, Zareba W, Schwartz PJ, Schulze-Bahr E, Etheridge SP, Priori SG, and Ackerman MJ.
- Abstract
Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. Results: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6-52.2]; P=0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3-10.8], P=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 0
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- 2020
15. 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, Sacilotto, L, Sarquella-Brugada, G, Campuzano, O, Nof, E, Anastasakis, A, Sansone, V, Jimenez-Jaimez, J, Cruz, F, Sanchez-Quinones, J, Hernandez-Afonso, J, Fuentes, M, Sredniawa, B, Garoufi, A, Andrsova, I, Izquierdo, M, Marinov, R, Danon, A, Exposito-Garcia, V, Garcia-Fernandez, A, Munoz-Esparza, C, Ortiz, M, Zienciuk-Krajka, A, Tavazzani, E, Monteforte, N, Bloise, R, Marino, M, Memmi, M, Napolitano, C, Zorio, E, Monserrat, L, Bagnardi, V, Priori, S, 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., Sanchez-Quinones J., Hernandez-Afonso J., Fuentes M. E., Sredniawa B., Garoufi A., Andrsova I., Izquierdo M., Marinov R., Danon A., Exposito-Garcia V., Garcia-Fernandez A., Munoz-Esparza C., Ortiz 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., Mazzanti, A, Guz, D, Trancuccio, A, Pagan, E, Kukavica, D, Chargeishvili, T, Olivetti, N, Biernacka, E, Sacilotto, L, Sarquella-Brugada, G, Campuzano, O, Nof, E, Anastasakis, A, Sansone, V, Jimenez-Jaimez, J, Cruz, F, Sanchez-Quinones, J, Hernandez-Afonso, J, Fuentes, M, Sredniawa, B, Garoufi, A, Andrsova, I, Izquierdo, M, Marinov, R, Danon, A, Exposito-Garcia, V, Garcia-Fernandez, A, Munoz-Esparza, C, Ortiz, M, Zienciuk-Krajka, A, Tavazzani, E, Monteforte, N, Bloise, R, Marino, M, Memmi, M, Napolitano, C, Zorio, E, Monserrat, L, Bagnardi, V, Priori, S, 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., Sanchez-Quinones J., Hernandez-Afonso J., Fuentes M. E., Sredniawa B., Garoufi A., Andrsova I., Izquierdo M., Marinov R., Danon A., Exposito-Garcia V., Garcia-Fernandez A., Munoz-Esparza C., Ortiz M., Zienciuk-Krajka A., Tavazzani E., Monteforte N., Bloise R., Marino M., Memmi M., Napolitano C., Zorio E., Monserrat L., Bagnardi V., and 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.
- Published
- 2020
16. Assessment of absolute risk of life-threatening cardiac events in long QT syndrome patients
- Author
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Wang, M, Peterson, D, Pagan, E, Bagnardi, V, Mazzanti, A, Mcnitt, S, Rich, D, Seplaki, C, Kutyifa, V, Polonsky, B, Barsheshet, A, Kukavica, D, Rosero, S, Goldenberg, I, Priori, S, Zareba, W, Wang, M, Peterson, D, Pagan, E, Bagnardi, V, Mazzanti, A, Mcnitt, S, Rich, D, Seplaki, C, Kutyifa, V, Polonsky, B, Barsheshet, A, Kukavica, D, Rosero, S, Goldenberg, I, Priori, S, and Zareba, W
- Abstract
Background: Risk stratification in long QT syndrome (LQTS) patients is important for optimizing patient care and informing clinical decision making. We developed a risk prediction algorithm with prediction of 5-year absolute risk of the first life-threatening arrhythmic event [defined as aborted cardiac arrest, sudden cardiac death, or appropriate implantable cardioverter defibrillator (ICD) shock] in LQTS patients, accounting for individual risk factors and their changes over time. Methods: Rochester-based LQTS Registry included the phenotypic cohort consisting of 1,509 LQTS patients with a QTc ≥ 470 ms, and the genotypic cohort including 1,288 patients with single LQT1, LQT2, or LQT3 mutation. We developed two separate risk prediction models which included pre-specified time-dependent covariates of beta-blocker use, syncope (never, syncope while off beta blockers, and syncope while on beta blockers), and sex by age < and ≥13 years, baseline QTc, and genotype (for the genotypic cohort only). Follow-up started from enrollment in the registry and was censored at patients’ 50s birthday, date of death due to reasons other than sudden cardiac death, or last contact, whichever occurred first. The predictive models were externally validated in an independent cohort of 1,481 LQTS patients from Pavia, Italy. Results: In Rochester dataset, there were 77 endpoints in the phenotypic cohort during a median follow-up of 9.0 years, and 47 endpoints in the genotypic cohort during a median follow-up of 9.8 years. The time-dependent extension of Harrell’s generalized C-statistics for the phenotypic model and genotypic model were 0.784 (95% CI: 0.740–0.827) and 0.785 (95% CI: 0.721–0.849), respectively, in the Rochester cohort. The C-statistics obtained from external validation in the Pavia cohort were 0.700 (95% CI: 0.610–0.790) and 0.711 (95% CI: 0.631–0.792) for the two models, respectively. Based on the above models, an online risk calculator estimating a 5-year risk of life-t
- Published
- 2022
17. Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk)
- Author
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Mazzanti, A, Trancuccio, A, Kukavica, D, Pagan, E, Wang, M, Mohsin, M, Peterson, D, Bagnardi, V, Zareba, W, Priori, S, Mazzanti, Andrea, Trancuccio, Alessandro, Kukavica, Deni, Pagan, Eleonora, Wang, Meng, Mohsin, Muhammed, Peterson, Derick, Bagnardi, Vincenzo, Zareba, Wojciech, Priori, Silvia G, Mazzanti, A, Trancuccio, A, Kukavica, D, Pagan, E, Wang, M, Mohsin, M, Peterson, D, Bagnardi, V, Zareba, W, Priori, S, Mazzanti, Andrea, Trancuccio, Alessandro, Kukavica, Deni, Pagan, Eleonora, Wang, Meng, Mohsin, Muhammed, Peterson, Derick, Bagnardi, Vincenzo, Zareba, Wojciech, and Priori, Silvia G
- Abstract
Aims: Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model. Methods and results: The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61-0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70-0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3-13.6). Conclusion: The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants.
- Published
- 2022
18. Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1
- Author
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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
- Published
- 2020
19. Characterization of arrhythmic presentation in patients with arrhythmogenic cardiomyopathy
- Author
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Chargeishvili, T, primary, Mazzanti, A, additional, Kukavica, D, additional, Marelli, S, additional, Trancuccio, A, additional, Monteforte, N, additional, Bloise, R, additional, Marino, M, additional, Morini, M, additional, Napolitano, C, additional, and Priori, S.G, additional
- Published
- 2020
- Full Text
- View/download PDF
20. Is mexiletine ready for prime time in patients with Type 2 Long QT Syndrome?
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Mazzanti, A, primary, Chargeishvili, T, additional, Kukavica, D, additional, Marino, M, additional, Morini, M, additional, Trancuccio, A, additional, Marelli, S, additional, Monteforte, N, additional, Bloise, R, additional, Napolitano, C, additional, and Priori, S.G, additional
- Published
- 2020
- Full Text
- View/download PDF
21. Mutation site-specific risk profile in patients with Type 1 Long QT Syndrome
- Author
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Trancuccio, A, primary, Mazzanti, A, additional, Kukavica, D, additional, Marino, M, additional, Monteforte, N, additional, Bloise, R, additional, Braghieri, L, additional, Memmi, M, additional, Morini, M, additional, Napolitano, C, additional, and Priori, S.G, additional
- Published
- 2020
- Full Text
- View/download PDF
22. Automated screening tool for Subcutaneous Implantable Defibrillator in Brugada syndrome has a high eligibility rate which is predicted by simple electrocardiographic parameters
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Marelli, S, primary, Kukavica, D, additional, Mazzanti, A, additional, Chargeishvili, T, additional, Trancuccio, A, additional, Monteforte, N, additional, Bloise, R, additional, Marino, M, additional, Napolitano, C, additional, and Priori, S.G, additional
- Published
- 2020
- Full Text
- View/download PDF
23. 338Myocardial deformation imaging for the assessment of left ventricular function in arrhythmogenic right ventricular cardiomyopathy: a feature tracking cardiac magnetic resonance study
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Stolfo, D, primary, Della Paolera, M, additional, Mazzanti, A, additional, Kukavica, D, additional, Vitrella, G, additional, Merlo, M, additional, Muser, D, additional, Pagnan, L, additional, Eshja, E, additional, De Luca, A, additional, Altinier, A, additional, Barbati, G, additional, Proclemer, A, additional, Priori, S, additional, and Sinagra, G, additional
- Published
- 2019
- Full Text
- View/download PDF
24. 338 Myocardial deformation imaging for the assessment of left ventricular function in arrhythmogenic right ventricular cardiomyopathy: a feature tracking cardiac magnetic resonance study.
- Author
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Stolfo, D, Paolera, M Della, Mazzanti, A, Kukavica, D, Vitrella, G, Merlo, M, Muser, D, Pagnan, L, Eshja, E, Luca, A De, Altinier, A, Barbati, G, Proclemer, A, Priori, S, and Sinagra, G
- Subjects
CONFERENCES & conventions ,ECHOCARDIOGRAPHY ,LEFT heart ventricle ,HEART physiology ,ARRHYTHMOGENIC right ventricular dysplasia - Published
- 2019
- Full Text
- View/download PDF
25. MYOCARDIAL DEFORMATION IMAGING FOR THE ASSESSMENT OF LEFT VENTRICULAR FUNCTION IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY: A FEATURE TRACKING CARDIAC MAGNETIC RESONANCE STUDY
- Author
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Stolfo, D., Della Paolera, M., Andrea Mazzanti, Kukavica, D., Vitrella, G., Merlo, M., Muser, M. D., Pagnan, L., Eshja, E., Luca, A., Cappelletto, C., Mase, M., Cittar, M., Crosera, L., Barbati, G., Dal Ferro, M., Proclemer, A., Priori, S., and Sinagra, G.
26. Myocardial deformation imaging for the assessment of left ventricular function in arrhythmogenic right ventricular cardiomyopathy: a feature tracking cardiac magnetic resonance study
- Author
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Stolfo, D., Della Paolera, M., Andrea Mazzanti, Kukavica, D., Vitrella, G., Merlo, M., Muser, D., Pagnan, L., Eshja, E., Luca, A., Altinier, A., Barbati, G., Proclemer, A., Priori, S., and Sinagra, G.
27. Value of 3D echocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy
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Karima Addetia, Andrea Mazzanti, Riccardo Maragna, Lorenzo Monti, Megan Yamat, Deni Kukavica, Eleonora Pagan, Kanako Kishiki, Aldo Prado, Maira Marino, Vincenzo Bagnardi, Silvia Priori, Roberto M Lang, Addetia, K, Mazzanti, A, Maragna, R, Monti, L, Yamat, M, Kukavica, D, Pagan, E, Kishiki, K, Prado, A, Marino, M, Bagnardi, V, Priori, S, and Lang, R
- Subjects
arrhythmogenic right ventricular cardiomyopathy ,Task Force Criteria for ARVC ,three-dimensional echocardiography ,echocardiography ,Radiology, Nuclear Medicine and imaging ,General Medicine ,Cardiology and Cardiovascular Medicine ,cardiovascular MRI - Abstract
Aims The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC. Methods and results Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE–cMRI and 2DE–3DE approaches. Using the 2DE–cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE–3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44–0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage. Conclusion The combination of 2DE–3DE for ARVC diagnosis is comparable to the conventional 2DE–cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA.
- Published
- 2023
28. Assessment of absolute risk of life-threatening cardiac events in long QT syndrome patients
- Author
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Meng Wang, Derick R. Peterson, Eleonora Pagan, Vincenzo Bagnardi, Andrea Mazzanti, Scott McNitt, David Q. Rich, Christopher L. Seplaki, Valentina Kutyifa, Bronislava Polonsky, Alon Barsheshet, Deni Kukavica, Spencer Rosero, Ilan Goldenberg, Silvia Priori, Wojciech Zareba, Wang, M, Peterson, D, Pagan, E, Bagnardi, V, Mazzanti, A, Mcnitt, S, Rich, D, Seplaki, C, Kutyifa, V, Polonsky, B, Barsheshet, A, Kukavica, D, Rosero, S, Goldenberg, I, Priori, S, Zareba, W, and National Institutes of Health (Estados Unidos)
- Subjects
beta blocker ,risk prediction ,implantable cardioverter defibrillator ,syncope ,long QT syndrome ,sex ,cardiac arrest ,Cardiology and Cardiovascular Medicine - Abstract
BackgroundRisk stratification in long QT syndrome (LQTS) patients is important for optimizing patient care and informing clinical decision making. We developed a risk prediction algorithm with prediction of 5-year absolute risk of the first life-threatening arrhythmic event [defined as aborted cardiac arrest, sudden cardiac death, or appropriate implantable cardioverter defibrillator (ICD) shock] in LQTS patients, accounting for individual risk factors and their changes over time.MethodsRochester-based LQTS Registry included the phenotypic cohort consisting of 1,509 LQTS patients with a QTc ≥ 470 ms, and the genotypic cohort including 1,288 patients with single LQT1, LQT2, or LQT3 mutation. We developed two separate risk prediction models which included pre-specified time-dependent covariates of beta-blocker use, syncope (never, syncope while off beta blockers, and syncope while on beta blockers), and sex by age < and ≥13 years, baseline QTc, and genotype (for the genotypic cohort only). Follow-up started from enrollment in the registry and was censored at patients’ 50s birthday, date of death due to reasons other than sudden cardiac death, or last contact, whichever occurred first. The predictive models were externally validated in an independent cohort of 1,481 LQTS patients from Pavia, Italy.ResultsIn Rochester dataset, there were 77 endpoints in the phenotypic cohort during a median follow-up of 9.0 years, and 47 endpoints in the genotypic cohort during a median follow-up of 9.8 years. The time-dependent extension of Harrell’s generalized C-statistics for the phenotypic model and genotypic model were 0.784 (95% CI: 0.740–0.827) and 0.785 (95% CI: 0.721–0.849), respectively, in the Rochester cohort. The C-statistics obtained from external validation in the Pavia cohort were 0.700 (95% CI: 0.610–0.790) and 0.711 (95% CI: 0.631–0.792) for the two models, respectively. Based on the above models, an online risk calculator estimating a 5-year risk of life-threatening arrhythmic events was developed.ConclusionThis study developed two risk prediction algorithms for phenotype and genotype positive LQTS patients separately. The estimated 5-year absolute risk can be used to quantify a LQTS patient’s risk of developing life-threatening arrhythmic events and thus assisting in clinical decision making regarding prophylactic ICD therapy.
- Published
- 2022
- Full Text
- View/download PDF
29. Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk): comment-Authors' reply
- Author
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Andrea Mazzanti, Alessandro Trancuccio, Deni Kukavica, Eleonora Pagan, Meng Wang, Muhammed Mohsin, Derick Peterson, Vincenzo Bagnardi, Wojciech Zareba, Silvia G Priori, Mazzanti, A, Trancuccio, A, Kukavica, D, Pagan, E, Wang, M, Mohsin, M, Peterson, D, Bagnardi, V, Zareba, W, and Priori, S
- Subjects
Long QT Syndrome ,Death, Sudden, Cardiac ,Physiology (medical) ,Humans ,Cardiology and Cardiovascular Medicine ,Human - Published
- 2022
30. Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk)
- Author
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Alessandro Trancuccio, Vincenzo Bagnardi, Meng Wang, Andrea Mazzanti, Wojciech Zareba, Silvia G. Priori, Muhammed Mohsin, Derick R. Peterson, Deni Kukavica, Eleonora Pagan, Mazzanti, A, Trancuccio, A, Kukavica, D, Pagan, E, Wang, M, Mohsin, M, Peterson, D, Bagnardi, V, Zareba, W, and Priori, S
- Subjects
medicine.medical_specialty ,Risk model ,medicine.medical_treatment ,Long QT syndrome ,QT interval ,Implantable cardioverter-defibrillator ,Sudden cardiac death ,Electrocardiography ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Risk stratification ,Framingham Risk Score ,business.industry ,Arrhythmias, Cardiac ,medicine.disease ,Confidence interval ,Long QT Syndrome ,Death, Sudden, Cardiac ,Cohort ,Number needed to treat ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model. Methods and results The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61–0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70–0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3–13.6). Conclusion The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants.
- Published
- 2021
31. Arrhythmic Mitral Valve Prolapse: Introducing an Era of Multimodality Imaging-Based Diagnosis and Risk Stratification
- Author
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Mauro Pepi, Andrea Baggiano, Andrea Mazzanti, Marco Guglielmo, Manuela Muratori, Deni Kukavica, Silvia G. Priori, Valentina Mantegazza, Alessandro Trancuccio, Giuseppe Muscogiuri, Carlo Arnò, Gianluca Pontone, Laura Fusini, Gloria Tamborini, Kukavica, D, Guglielmo, M, Baggiano, A, Muscogiuri, G, Fusini, L, Muratori, M, Tamborini, G, Mantegazza, V, Trancuccio, A, Arnò, C, Mazzanti, A, Pepi, M, Priori, S, and Pontone, G
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medicine.medical_specialty ,Clinical Biochemistry ,Settore MED/11 - Malattie dell'Apparato Cardiovascolare ,Review ,030204 cardiovascular system & hematology ,arrhythmia ,cardiovascular magnetic resonance ,echocardiography ,mitral valve prolapse ,multimodality imaging ,risk factors ,sudden cardiac death ,Sudden cardiac death ,03 medical and health sciences ,0302 clinical medicine ,Mitral valve ,Internal medicine ,Epidemiology ,medicine ,Mitral valve prolapse ,In patient ,030212 general & internal medicine ,cardiovascular diseases ,lcsh:R5-920 ,business.industry ,medicine.disease ,Young age ,medicine.anatomical_structure ,Risk stratification ,Etiology ,Cardiology ,cardiovascular system ,Risk factor ,business ,lcsh:Medicine (General) - Abstract
Mitral valve prolapse is a common cardiac condition, with an estimated prevalence between 1% and 3%. Most patients have a benign course, but ever since its initial description mitral valve prolapse has been associated to sudden cardiac death. Although the causal relationship between mitral valve prolapse and sudden cardiac death has never been clearly demonstrated, different factors have been implicated in arrhythmogenesis in patients with mitral valve prolapse. In this work, we offer a comprehensive overview of the etiology and the genetic background, epidemiology, pathophysiology, and we focus on the state-of-the-art imaging-based diagnosis of mitral valve prolapse. Going beyond the classical, well-described clinical factors, such as young age, female gender and auscultatory findings, we investigate multimodality imaging features, such as alterations of anatomy and function of the mitral valve and its leaflets, the structural and contractile anomalies of the myocardium, all of which have been associated to sudden cardiac death. This research received no external funding Sí
- Published
- 2021
32. Additional diagnostic value of cardiac magnetic resonance feature tracking in patients with biopsy-proven arrhythmogenic cardiomyopathy
- Author
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Marco Guglielmo, Andrea Annoni, Rocco Mollace, Maria Elisabetta Mancini, Giuseppe Muscogiuri, Edoardo Conte, Saima Mushtaq, Elena Sommariva, Claudio Tondo, Andrea Baggiano, Mario Babbaro, Cristina Basso, Ada Collevecchio, Mark G. Rabbat, Alessio Gasperetti, Deni Kukavica, Alberto Formenti, Antonio Dello Russo, Stefania Rizzo, Daniele Andreini, Mauro Pepi, Michela Casella, Monica De Gaspari, Francesca Ricci, Stefano Scafuri, Silvia G. Priori, Andrea Igoren Guaricci, Rita Sicuso, Gianluca Pontone, Laura Fusini, Muscogiuri, G, Fusini, L, Ricci, F, Sicuso, R, Guglielmo, M, Baggiano, A, Gasperetti, A, Casella, M, Mushtaq, S, Conte, E, Annoni, A, Formenti, A, Mancini, M, Babbaro, M, Mollace, R, Collevecchio, A, Scafuri, S, Kukavica, D, Andreini, D, Basso, C, Rizzo, S, De Gaspari, M, Priori, S, Dello Russo, A, Tondo, C, Pepi, M, Sommariva, E, Rabbat, M, Guaricci, A, and Pontone, G
- Subjects
medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Myocardial biopsy ,Arrhythmogenic cardiomyopathy ,Myocardial strain ,Biopsy ,Cardiomyopathy ,Contrast Media ,Magnetic Resonance Imaging, Cine ,Gadolinium ,Ventricular Function, Left ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Late gadolinium enhancement ,In patient ,cardiovascular diseases ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Stroke Volume ,medicine.disease ,cardiovascular system ,Cardiology ,Feature tracking ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business ,Cardiac magnetic resonance ,circulatory and respiratory physiology - Abstract
Background: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved. Methods: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF
- Published
- 2021
33. An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition
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Julia Cadrin-Tourigny, Dan M. Roden, Valentina Kutyifa, Henry J. Duff, Robert M. Gow, Marco V Perez, Eric Vittinghoff, Wataru Shimizu, Birgit Stallmeyer, Linda M. Knight, Lia Crotti, Michael H. Gollob, Silvia G. Priori, Rafik Tadros, Juan Pablo Kaski, Gregory M. Marcus, S. Yukiko Asaki, Thomas M. Roston, Sharmila Udupa, Takeshi Aiba, Deni Kukavica, Peter J. Schwartz, Nikhil Chavali, M. Benjamin Shoemaker, Carla Spazzolini, Christopher S. Simpson, Fabrizio Drago, Yanushi D. Wijeyeratne, J. Martijn Bos, Sven Dittmann, John R. Giudicessi, Eric Schulze-Bahr, Peter S. Fischbach, Anwar Baban, Keiko Shimamoto, Arthur A. M. Wilde, Jonathan R. Skinner, Jason D. Roberts, Brynn E. Dechert, Peter F. Aziz, Andrew P. Landstrom, Andrea Mazzanti, Elijah R. Behr, Jacob Tfelt-Hansen, Dominic Abrams, Elizabeth S. Kaufman, Izabela Tuleta, Alison Muir, Maisoon D. Yousif, Lorne J. Gula, Michael J. Ackerman, Wojciech Zareba, Imane El Hajjaji, Christopher L. Johnsrude, Melvin M. Scheinman, Susan P. Etheridge, Peter Leong-Sit, Luciana Marcondes, Andrew D. Krahn, Cardiology, ACS - Heart failure & arrhythmias, Roberts, J, Asaki, S, Mazzanti, A, Bos, J, Tuleta, I, Muir, A, Crotti, L, Krahn, A, Kutyifa, V, Shoemaker, M, Johnsrude, C, Aiba, T, Marcondes, L, Baban, A, Udupa, S, Dechert, B, Fischbach, P, Knight, L, Vittinghoff, E, Kukavica, D, Stallmeyer, B, Giudicessi, J, Spazzolini, C, Shimamoto, K, Tadros, R, Cadrin-Tourigny, J, Duff, H, Simpson, C, Roston, T, Wijeyeratne, Y, El Hajjaji, I, Yousif, M, Gula, L, Leong-Sit, P, Chavali, N, Landstrom, A, Marcus, G, Dittmann, S, Wilde, A, Behr, E, Tfelt-Hansen, J, Scheinman, M, Perez, M, Kaski, J, Gow, R, Drago, F, Aziz, P, Abrams, D, Gollob, M, Skinner, J, Shimizu, W, Kaufman, E, Roden, D, Zareba, W, Schwartz, P, Schulze-Bahr, E, Etheridge, S, Priori, S, and Ackerman, M
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Male ,Proband ,Potassium Channels ,Penetrance ,Cardiorespiratory Medicine and Haematology ,030204 cardiovascular system & hematology ,Cardiovascular ,Sudden cardiac death ,Electrocardiography ,0302 clinical medicine ,Genotype ,2.1 Biological and endogenous factors ,Medicine ,genetics ,Registries ,Aetiology ,0303 health sciences ,Hazard ratio ,Voltage-Gated ,Middle Aged ,Death ,Heart Disease ,Public Health and Health Services ,Female ,Cardiology and Cardiovascular Medicine ,Cardiac ,Adult ,medicine.medical_specialty ,Adolescent ,Long QT syndrome ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Electric Countershock ,BIO/18 - GENETICA ,arrhythmia ,QT interval ,Article ,sudden cardiac death ,03 medical and health sciences ,Clinical Research ,Physiology (medical) ,Internal medicine ,Genetics ,long QT syndrome ,Humans ,penetrance ,030304 developmental biology ,business.industry ,Proportional hazards model ,Human Genome ,MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,medicine.disease ,Sudden ,Heart Arrest ,Cardiovascular System & Hematology ,genetic ,business - Abstract
Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. Results: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P P =0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3–10.8], P =0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). Conclusions: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.
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- 2020
34. Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1
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Eyal Nof, Fernando E.S. Cruz, Victor Expósito-García, Luciana Sacilotto, Andrea Mazzanti, Jessica Sánchez-Quiñones, Elżbieta Katarzyna Biernacka, Esther Zorio, Deni Kukavica, Carmen Muñoz-Esparza, Julio Hernandez-Afonso, Elisa Tavazzani, Oscar Campuzano, Asaf Danon, Juan Jiménez-Jáimez, Martín Ortiz, Tekla Chargeishvili, Lorenzo Monserrat, Agnieszka Zienciuk-Krajka, Aristides Anastasakis, Carlo Napolitano, Eleonora Pagan, Maira Marino, Dmitri Guz, Amaya Garcia-Fernandez, Mirella Memmi, Beata Średniawa, Natália Olivetti, Valeria A. Sansone, Rumen Marinov, Georgia Sarquella-Brugada, Maite Izquierdo, Nicola Monteforte, Raffaella Bloise, María Eugenia Fuentes, Irena Andršová, Vincenzo Bagnardi, Silvia G. Priori, Alessandro Trancuccio, Anastasia Garoufi, Mazzanti, A, Guz, D, Trancuccio, A, Pagan, E, Kukavica, D, Chargeishvili, T, Olivetti, N, Biernacka, E, Sacilotto, L, Sarquella-Brugada, G, Campuzano, O, Nof, E, Anastasakis, A, Sansone, V, Jimenez-Jaimez, J, Cruz, F, Sanchez-Quinones, J, Hernandez-Afonso, J, Fuentes, M, Sredniawa, B, Garoufi, A, Andrsova, I, Izquierdo, M, Marinov, R, Danon, A, Exposito-Garcia, V, Garcia-Fernandez, A, Munoz-Esparza, C, Ortiz, M, Zienciuk-Krajka, A, Tavazzani, E, Monteforte, N, Bloise, R, Marino, M, Memmi, M, Napolitano, C, Zorio, E, Monserrat, L, Bagnardi, V, and Priori, S
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Male ,Databases, Factual ,Amiodarone ,030204 cardiovascular system & hematology ,Sudden cardiac death ,Electrocardiography ,0302 clinical medicine ,Interquartile range ,genetics ,030212 general & internal medicine ,Child ,sudden cardiac death, genetics, inherited arrhythmias, KCNJ2, life-threatening arrhythmic events ,Andersen Syndrome ,Muscle Weakness ,Hazard ratio ,Middle Aged ,3. Good health ,Defibrillators, Implantable ,Natural history ,Child, Preschool ,Risk stratification ,Cohort ,Female ,Cardiology and Cardiovascular Medicine ,Anti-Arrhythmia Agents ,inherited arrhythmias ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Adrenergic beta-Antagonists ,Risk Assessment ,sudden cardiac death ,Syncope ,life- threatening arrhythmic events ,03 medical and health sciences ,Young Adult ,Andersen–Tawil syndrome ,Internal medicine ,medicine ,Humans ,Genetic Testing ,KCNJ2 ,Potassium Channels, Inwardly Rectifying ,KCNJ2, genetics, inherited arrhythmias, life-threatening arrhythmic events, sudden cardiac death ,business.industry ,Infant ,Arrhythmias, Cardiac ,medicine.disease ,life-threatening arrhythmic events ,Death, Sudden, Cardiac ,Mutation ,Tachycardia, Ventricular ,business - 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. (C) 2020 Published by Elsevier on behalf of the American College of Cardiology Foundation.
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- 2019
35. Prevention of Sudden Death and Management of Ventricular Arrhythmias in Arrhythmogenic Cardiomyopathy.
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Trancuccio A, Kukavica D, Sugamiele A, Mazzanti A, and Priori SG
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- Humans, Arrhythmias, Cardiac etiology, Death, Sudden, Cardiac etiology, Myocardium, Arrhythmogenic Right Ventricular Dysplasia complications, Defibrillators, Implantable adverse effects
- Abstract
Arrhythmogenic cardiomyopathy is an umbrella term for a group of inherited diseases of the cardiac muscle characterized by progressive fibro-fatty replacement of the myocardium. As suggested by the name, the disease confers electrical instability to the heart and increases the risk of the development of life-threatening arrhythmias, representing one of the leading causes of sudden cardiac death (SCD), especially in young athletes. In this review, the authors review the current knowledge of the disease, highlighting the state-of-the-art approaches to the prevention of the occurrence of SCD., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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36. Characterization of Skeletal Muscle Biopsy and Derived Myoblasts in a Patient Carrying Arg14del Mutation in Phospholamban Gene.
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Zanotti S, Ripolone M, Napoli L, Velardo D, Salani S, Ciscato P, Priori S, Kukavica D, Mazzanti A, Diamanti L, Vegezzi E, Moggio M, Corti S, Comi G, and Sciacco M
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- Male, Biopsy, Mutation genetics, Myoblasts metabolism, Humans, Calcium-Binding Proteins genetics, Calcium-Binding Proteins metabolism, Muscle, Skeletal metabolism
- Abstract
Phospholamban is involved in the regulation of the activity and storage of calcium in cardiac muscle. Several mutations have been identified in the PLN gene causing cardiac disease associated with arrhythmogenic and dilated cardiomyopathy. The patho-mechanism underlying PLN mutations is not fully understood and a specific therapy is not yet available. PLN mutated patients have been deeply investigated in cardiac muscle, but very little is known about the effect of PLN mutations in skeletal muscle. In this study, we investigated both histological and functional features in skeletal muscle tissue and muscle-derived myoblasts from an Italian patient carrying the Arg14del mutation in PLN . The patient has a cardiac phenotype, but he also reported lower limb fatigability, cramps and fasciculations. The evaluation of a skeletal muscle biopsy showed histological, immunohistochemical and ultrastructural alterations. In particular, we detected an increase in the number of centronucleated fibers and a reduction in the fiber cross sectional area, an alteration in p62, LC3 and VCP proteins and the formation of perinuclear aggresomes. Furthermore, the patient's myoblasts showed a greater propensity to form aggresomes, even more marked after proteasome inhibition compared with control cells. Further genetic and functional studies are necessary to understand whether a definition of PLN myopathy, or cardiomyopathy plus , can be introduced for selected cases with clinical evidence of skeletal muscle involvement. Including skeletal muscle examination in the diagnostic process of PLN -mutated patients can help clarify this issue.
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- 2023
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37. Value of 3D echocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.
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Addetia K, Mazzanti A, Maragna R, Monti L, Yamat M, Kukavica D, Pagan E, Kishiki K, Prado A, Marino M, Bagnardi V, Priori S, and Lang RM
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- Humans, Heart Ventricles diagnostic imaging, Magnetic Resonance Imaging methods, Echocardiography methods, Arrhythmogenic Right Ventricular Dysplasia, Echocardiography, Three-Dimensional methods
- Abstract
Aims: The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC., Methods and Results: Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE-cMRI and 2DE-3DE approaches. Using the 2DE-cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE-3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44-0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage., Conclusion: The combination of 2DE-3DE for ARVC diagnosis is comparable to the conventional 2DE-cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA., Competing Interests: Conflict of interest: R.M.L. serves on the Speakers’ and advisory bureau, and has received research grants from Philips Medical Imaging. All other authors have no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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38. Unexpected impairment of I Na underpins reentrant arrhythmias in a knock-in swine model of Timothy syndrome.
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Porta-Sánchez A, Mazzanti A, Tarifa C, Kukavica D, Trancuccio A, Mohsin M, Zanfrini E, Perota A, Duchi R, Hernandez-Lopez K, Jáuregui-Abularach ME, Pergola V, Fernandez E, Bongianino R, Tavazzani E, Gambelli P, Memmi M, Scacchi S, Pavarino LF, Franzone PC, Lentini G, Filgueiras-Rama D, Galli C, Santiago DJ, and Priori SG
- Abstract
Timothy syndrome 1 (TS1) is a multi-organ form of long QT syndrome associated with life-threatening cardiac arrhythmias, the organ-level dynamics of which remain unclear. In this study, we developed and characterized a novel porcine model of TS1 carrying the causative p.Gly406Arg mutation in CACNA1C , known to impair Ca
V 1.2 channel inactivation. Our model fully recapitulated the human disease with prolonged QT interval and arrhythmic mortality. Electroanatomical mapping revealed the presence of a functional substrate vulnerable to reentry, stemming from an unforeseen constitutional slowing of cardiac activation. This signature substrate of TS1 was reliably identified using the reentry vulnerability index, which, we further demonstrate, can be used as a benchmark for assessing treatment efficacy, as shown by testing of multiple clinical and preclinical anti-arrhythmic compounds. Notably, in vitro experiments showed that TS1 cardiomyocytes display Ca2+ overload and decreased peak INa current, providing a rationale for the arrhythmogenic slowing of impulse propagation in vivo., Competing Interests: Competing interestsA.P., R.D. and C.G. are employees of Avantea (Cremona, Italy). All other authors declare no conflict of interest., (© The Author(s) 2023.)- Published
- 2023
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39. Assessment of absolute risk of life-threatening cardiac events in long QT syndrome patients.
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Wang M, Peterson DR, Pagan E, Bagnardi V, Mazzanti A, McNitt S, Rich DQ, Seplaki CL, Kutyifa V, Polonsky B, Barsheshet A, Kukavica D, Rosero S, Goldenberg I, Priori S, and Zareba W
- Abstract
Background: Risk stratification in long QT syndrome (LQTS) patients is important for optimizing patient care and informing clinical decision making. We developed a risk prediction algorithm with prediction of 5-year absolute risk of the first life-threatening arrhythmic event [defined as aborted cardiac arrest, sudden cardiac death, or appropriate implantable cardioverter defibrillator (ICD) shock] in LQTS patients, accounting for individual risk factors and their changes over time., Methods: Rochester-based LQTS Registry included the phenotypic cohort consisting of 1,509 LQTS patients with a QTc ≥ 470 ms, and the genotypic cohort including 1,288 patients with single LQT1, LQT2, or LQT3 mutation. We developed two separate risk prediction models which included pre-specified time-dependent covariates of beta-blocker use, syncope (never, syncope while off beta blockers, and syncope while on beta blockers), and sex by age < and ≥13 years, baseline QTc, and genotype (for the genotypic cohort only). Follow-up started from enrollment in the registry and was censored at patients' 50s birthday, date of death due to reasons other than sudden cardiac death, or last contact, whichever occurred first. The predictive models were externally validated in an independent cohort of 1,481 LQTS patients from Pavia, Italy., Results: In Rochester dataset, there were 77 endpoints in the phenotypic cohort during a median follow-up of 9.0 years, and 47 endpoints in the genotypic cohort during a median follow-up of 9.8 years. The time-dependent extension of Harrell's generalized C-statistics for the phenotypic model and genotypic model were 0.784 (95% CI: 0.740-0.827) and 0.785 (95% CI: 0.721-0.849), respectively, in the Rochester cohort. The C-statistics obtained from external validation in the Pavia cohort were 0.700 (95% CI: 0.610-0.790) and 0.711 (95% CI: 0.631-0.792) for the two models, respectively. Based on the above models, an online risk calculator estimating a 5-year risk of life-threatening arrhythmic events was developed., Conclusion: This study developed two risk prediction algorithms for phenotype and genotype positive LQTS patients separately. The estimated 5-year absolute risk can be used to quantify a LQTS patient's risk of developing life-threatening arrhythmic events and thus assisting in clinical decision making regarding prophylactic ICD therapy., 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 Wang, Peterson, Pagan, Bagnardi, Mazzanti, McNitt, Rich, Seplaki, Kutyifa, Polonsky, Barsheshet, Kukavica, Rosero, Goldenberg, Priori and Zareba.)
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- 2022
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40. Acute Myocarditis Associated With Desmosomal Gene Variants.
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Ammirati E, Raimondi F, Piriou N, Sardo Infirri L, Mohiddin SA, Mazzanti A, Shenoy C, Cavallari UA, Imazio M, Aquaro GD, Olivotto I, Pedrotti P, Sekhri N, Van de Heyning CM, Broeckx G, Peretto G, Guttmann O, Dellegrottaglie S, Scatteia A, Gentile P, Merlo M, Goldberg RI, Reyentovich A, Sciamanna C, Klaassen S, Poller W, Trankle CR, Abbate A, Keren A, Horowitz-Cederboim S, Cadrin-Tourigny J, Tadros R, Annoni GA, Bonoldi E, Toquet C, Marteau L, Probst V, Trochu JN, Kissopoulou A, Grosu A, Kukavica D, Trancuccio A, Gil C, Tini G, Pedrazzini M, Torchio M, Sinagra G, Gimeno JR, Bernasconi D, Valsecchi MG, Klingel K, Adler ED, Camici PG, and Cooper LT Jr
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- Gadolinium, Humans, Retrospective Studies, Stroke Volume, Troponin, Ventricular Function, Left, Young Adult, Heart Failure, Myocarditis genetics
- Abstract
Background: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown., Objectives: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV., Methods: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up., Results: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM., Conclusions: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk., Competing Interests: Funding Support and Author Disclosures Dr Ammirati has received a grant from the Italian Ministry of Health (GR-2019-12368506) and is a consultant for Kiniksa and Cytokinetics. Dr Adler is a consultant for Abbott, Abiomed, AstraZeneca, Endotronix, Ionis, Medtronic, and Novartis; is on the board of directors of Genstem Therapeutics; and is a shareholder of Rocket Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2022
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41. Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator.
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Jordà P, Bosman LP, Gasperetti A, Mazzanti A, Gourraud JB, Davies B, Frederiksen TC, Weidmann ZM, Di Marco A, Roberts JD, MacIntyre C, Seifer C, Delinière A, Alqarawi W, Kukavica D, Minois D, Trancuccio A, Arnaud M, Targetti M, Martino A, Oliviero G, Pipilas DC, Carbucicchio C, Compagnucci P, Dello Russo A, Olivotto I, Calò L, Lubitz SA, Cutler MJ, Chevalier P, Arbelo E, Priori SG, Healey JS, Calkins H, Casella M, Jensen HK, Tondo C, Tadros R, James CA, Krahn AD, and Cadrin-Tourigny J
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- Arrhythmias, Cardiac etiology, Death, Sudden, Cardiac epidemiology, Death, Sudden, Cardiac etiology, Death, Sudden, Cardiac prevention & control, Humans, Retrospective Studies, Risk Factors, Arrhythmogenic Right Ventricular Dysplasia complications, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Arrhythmogenic Right Ventricular Dysplasia therapy, Defibrillators, Implantable adverse effects
- Abstract
Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus., Methods and Results: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%., Conclusion: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC., Competing Interests: Conflicts of interest: C.M.: honoraria from Abbott, I.O.: grants, consulting fees or honoraria from BSM, Cytokinetics, Shire, Genzyme, Amicus, Menarini International, Boston Scientific, and Tenaya, S.A.L.: grants from BMS/Pfizer, Boehringer Ingelheim, fitbit, IBM, and consulting fees from BMS/Pfizer, Invitae, and Blackstone, J.S.H.: research grants from Boston Scientific, Abbott, and Medtronic and is on Scientific Advisory Board for Boston Scientific, H.K.J.: grant from Novo Nordisk foundation and honoraria from Abbott and Biosense Webster, H.C.: consultant for Medtronic Inc., Biosense Webster, Pfizer, and Abbott. He receives research support from Boston Scientific Corp. C.A.J. receives salary support from this grant and consulting fees from Pfizer, J. C.-T. consulting fees from BMS/Pfizer and Bayer., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)
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- 2022
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42. 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
- Subjects
- 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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43. Independent validation and clinical implications of the risk prediction model for long QT syndrome (1-2-3-LQTS-Risk).
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Mazzanti A, Trancuccio A, Kukavica D, Pagan E, Wang M, Mohsin M, Peterson D, Bagnardi V, Zareba W, and Priori SG
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- Arrhythmias, Cardiac, Death, Sudden, Cardiac, Electrocardiography, Humans, Longitudinal Studies, Prospective Studies, Risk Factors, Long QT Syndrome diagnosis, Long QT Syndrome genetics, Long QT Syndrome therapy
- Abstract
Aims: Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model., Methods and Results: The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61-0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70-0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3-13.6)., Conclusion: The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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44. Desmoplakin cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy: two distinct forms of cardiomyopathy?
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Kukavica D, Trancuccio A, Arnò C, Latini AC, Mazzanti A, and Priori SG
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- Desmoplakins genetics, Humans, Mutation, Phenotype, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Arrhythmogenic Right Ventricular Dysplasia genetics, Cardiomyopathies diagnosis, Cardiomyopathies genetics
- Abstract
The confirmation of a hypothesis that desmoplakin-related (DSP) cardiomyopathy could represent a distinct clinical entity from the classical, RV-dominant, form of arrhythmogenic cardiomyopathy (ACM), most frequently caused by PKP2 mutations, would without any shadow of doubt signify a turning point in the history of this disease. The concept of gene-specific diseases underneath the umbrella diagnosis of ACM would bring fundamental changes not only in the clinical, diagnostic and therapeutic approach, but also in terms of risk stratification, pushing the scientific community towards a more patient-centered view of the disease, similarly to what has already been done in other inherited arrhythmogenic disease (e.g., long QT syndrome [LQTS]). We provide a state-of-the-art review, starting with a brief historical framework to give the necessary context and better focus the question. Then, we proceed with a novel, genotype-to-phenotype-based comparison of the most important aspects of DSP-related cardiomyopathy with the classical, RV-dominant ACM: this allows us to ascertain not only that the differences between the forms exist, but are also clinically relevant and actionable, leading to the underrecognition of the atypical, DSP-related, LV-dominant forms when applying the current diagnostic criteria. These findings will usher an exciting era, in which the scientific community will try to answer a range of questions, starting from the reasons why different desmosomal mutations cause such different phenotypes.
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- 2022
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45. Dissecting haematoma of the interventricular septum.
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Kukavica D, Braggion G, and Pontone G
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- Hematoma diagnostic imaging, Hematoma etiology, Humans, Aortic Aneurysm, Sinus of Valsalva, Ventricular Septum diagnostic imaging
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- 2021
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46. Additional diagnostic value of cardiac magnetic resonance feature tracking in patients with biopsy-proven arrhythmogenic cardiomyopathy.
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Muscogiuri G, Fusini L, Ricci F, Sicuso R, Guglielmo M, Baggiano A, Gasperetti A, Casella M, Mushtaq S, Conte E, Annoni A, Formenti A, Mancini ME, Babbaro M, Mollace R, Collevecchio A, Scafuri S, Kukavica D, Andreini D, Basso C, Rizzo S, De Gaspari M, Priori S, Dello Russo A, Tondo C, Pepi M, Sommariva E, Rabbat M, Guaricci AI, and Pontone G
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- Biopsy, Gadolinium, Humans, Magnetic Resonance Imaging, Cine, Magnetic Resonance Spectroscopy, Predictive Value of Tests, Stroke Volume, Ventricular Function, Left, Cardiomyopathies, Contrast Media
- Abstract
Background: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved., Methods: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF<55%) and compared to an age and gender-matched control group. CMR datasets of all patients were analyzed to calculate LV indexed end-diastolic (LVEDi) and end-systolic (LVESi) volumes and RV indexed end-diastolic (RVEDi) and end-systolic (RVESi) volumes, both LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Moreover, LV and RV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were measured., Results: The AC patients showed both higher LVEDi (p:0.002) and RVEDi (p:0.017) and lower LVEF (p: 0.016) as compared to control patients. Moreover, AC patients showed impaired LV-GLS (p < 0.001), LV-GRS (p < 0.001), LV-GCS (p < 0.001) and RV-GRS (p:0.026) as compared to control subjects. Group1 patients showed a significant reduction of LV-GRS (p < 0.05) and LV-GCS p < 0.01) as compared to control subjects. At univariate analysis LV-GCS was the most discriminatory parameter between Group1 vs heathy subjects with an optimal cut-off of -15.8 (Sensitivity: 74%; Specificity: 10%)., Conclusions: In patients with AC biopsy-proven, CMR-FT could improve the diagnostic yield in the subset of patients who results negative for imaging TFC criteria resulting as useful gatekeeper for indication of myocardial biopsy in case of equivocal clinical and imaging presentation., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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47. Precision Medicine in Catecholaminergic Polymorphic Ventricular Tachycardia: JACC Focus Seminar 5/5.
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Priori SG, Mazzanti A, Santiago DJ, Kukavica D, Trancuccio A, and Kovacic JC
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- Humans, Precision Medicine, Tachycardia, Ventricular genetics, Tachycardia, Ventricular therapy
- Abstract
In this final of a 5-part Focus Seminar series on precision medicine, we focus on catecholaminergic polymorphic ventricular tachycardia (CPVT). This focus on CPVT allows us to take a "deep dive" and explore the full extent of the precision medicine opportunities for a single cardiovascular condition at a level that was not possible in the preceding articles. As a new paradigm presented in this article, it has become clear that CPVT can occur as either a typical or atypical form. Although there is a degree of overlap between the typical and atypical forms, it is notable that they arise due to different underlying genetic changes, likely exhibiting differing mechanisms of action, and presenting with different phenotypic features. The recognition of these differing forms of CPVT and their different etiologies and mechanisms is an important step toward implementing rapidly emerging precision medicine approaches that will tailor novel therapies to specific gene defects., Competing Interests: Funding Support and Author Disclosures This work was supported by ERC Advanced Grant N. 669387 and Telethon Grants N. GGP19134. Dr. Kovacic acknowledges research support from the National Institutes of Health (R01HL130423, R01HL135093, R01HL148167-01A1) and New South Wales health grant RG194194. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2021
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48. Arrhythmic Mitral Valve Prolapse: Introducing an Era of Multimodality Imaging-Based Diagnosis and Risk Stratification.
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Kukavica D, Guglielmo M, Baggiano A, Muscogiuri G, Fusini L, Muratori M, Tamborini G, Mantegazza V, Trancuccio A, Arnò C, Mazzanti A, Pepi M, Priori SG, and Pontone G
- Abstract
Mitral valve prolapse is a common cardiac condition, with an estimated prevalence between 1% and 3%. Most patients have a benign course, but ever since its initial description mitral valve prolapse has been associated to sudden cardiac death. Although the causal relationship between mitral valve prolapse and sudden cardiac death has never been clearly demonstrated, different factors have been implicated in arrhythmogenesis in patients with mitral valve prolapse. In this work, we offer a comprehensive overview of the etiology and the genetic background, epidemiology, pathophysiology, and we focus on the state-of-the-art imaging-based diagnosis of mitral valve prolapse. Going beyond the classical, well-described clinical factors, such as young age, female gender and auscultatory findings, we investigate multimodality imaging features, such as alterations of anatomy and function of the mitral valve and its leaflets, the structural and contractile anomalies of the myocardium, all of which have been associated to sudden cardiac death.
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- 2021
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49. 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
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- 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
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- 2020
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50. 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
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- 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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