Giovanni Peretto, Stefania Rizzo, Andrea Menegon, Andrea Villatore, Rengasayee Veeraraghavan, Davide Vignale, Valerio Castoldi, Laura Perani, Tamara Canu, Maria Carla Panzeri, Stefania Del Rosso, Rossana Norata, Martina Rocchi, Mila Della Barbera, Elena Rossi, Marco Cursi, Andrea Bergamaschi, Corrado Campochiaro, Giacomo De Luca, Marco Rasponi, Chiara Di Resta, Anna Palmisano, Paola Carrera, Luca Muzio, Alessandra Laura Giulia Pedrocchi, Letizia Leocani, Davide Lazzeroni, Francesca Sanvito, Simone Sala, Lorenzo Dagna, Paolo Guido Camici, Gianvito Martino, DeLisa Fairweather, Alida Linda Patrizia Caforio, Cristina Basso, Antonio Esposito, Leslie T Cooper, Paolo Della Bella
{"title":"炎性心肌病患者间插椎间盘异常与心律失常有关。","authors":"Giovanni Peretto, Stefania Rizzo, Andrea Menegon, Andrea Villatore, Rengasayee Veeraraghavan, Davide Vignale, Valerio Castoldi, Laura Perani, Tamara Canu, Maria Carla Panzeri, Stefania Del Rosso, Rossana Norata, Martina Rocchi, Mila Della Barbera, Elena Rossi, Marco Cursi, Andrea Bergamaschi, Corrado Campochiaro, Giacomo De Luca, Marco Rasponi, Chiara Di Resta, Anna Palmisano, Paola Carrera, Luca Muzio, Alessandra Laura Giulia Pedrocchi, Letizia Leocani, Davide Lazzeroni, Francesca Sanvito, Simone Sala, Lorenzo Dagna, Paolo Guido Camici, Gianvito Martino, DeLisa Fairweather, Alida Linda Patrizia Caforio, Cristina Basso, Antonio Esposito, Leslie T Cooper, Paolo Della Bella","doi":"10.1016/j.jacep.2025.02.025","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The relationship between intercalated disc abnormalities (IDAs) and arrhythmias in inflammatory cardiomyopathy (ICM) remains incompletely understood.</p><p><strong>Objectives: </strong>This study presents a pilot research that aimed to: 1) investigate the link between IDAs and arrhythmias in humans with ICM; and 2) compare findings in humans and mice with experimental autoimmune myocarditis (EAM).</p><p><strong>Methods: </strong>Humans with ICM (N = 316) investigated for either genetic or autoimmune IDAs were identified at a referral center. Ultrastructural analysis on biobanked tissue was performed to determine the average intercellular cleft width (ICW) between cardiac myocytes. IDA+ cases were compared with IDA- control subjects matched 1:1 by age, sex, and race/ethnicity. The primary endpoint was the occurrence of clinically demanding supraventricular or ventricular arrhythmias, recorded either by Holter electrocardiography or implanted devices during a 24-month prospective follow-up. The relationships between ICW and arrhythmias were compared in humans and male mice with EAM (n = 12).</p><p><strong>Results: </strong>Of 316 humans with ICM (mean age 45 ± 15 years, 63% male), 70 (22%) were IDA+ and 107 (34%) had arrhythmias on admission. IDA+ patients had greater ICW than control subjects (44 ± 8 nm vs 28 ± 4 nm; P < 0.001) and higher incidence of clinically demanding arrhythmias both at presentation (31 of 70 vs 9 of 70; P < 0.001) and during follow-up (44 of 70 vs 10 of 70; P < 0.001). In a multivariable model, IDAs predicted the occurrence of major ventricular arrhythmias by 24 months (HR: 3.0; 95% CI: 1.4-6.4; P = 0.004). In mice, arrhythmias were documented in 7 of 12 EAM cases and 0 of 6 control animals (P = 0.038). Increased ICW was found in close relationship with arrhythmias in both species (humans: 32 of 44 with vs 4 of 52 without arrhythmias; P < 0.001; mice: 7 of 8 with vs 0 of 4 without arrhythmias; P = 0.010), as well as with abnormal ventricular electrograms on viable murine myocardial tissue (5 of 6 vs 0 of 6; P = 0.015).</p><p><strong>Conclusions: </strong>As a shared trait between genetic and autoimmune ICM, IDAs are linked to arrhythmias in humans and find promising applications in the EAM mouse model.</p>","PeriodicalId":14573,"journal":{"name":"JACC. Clinical electrophysiology","volume":" ","pages":""},"PeriodicalIF":8.0000,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intercalated Disc Abnormalities Are Linked to Arrhythmias in Inflammatory Cardiomyopathy.\",\"authors\":\"Giovanni Peretto, Stefania Rizzo, Andrea Menegon, Andrea Villatore, Rengasayee Veeraraghavan, Davide Vignale, Valerio Castoldi, Laura Perani, Tamara Canu, Maria Carla Panzeri, Stefania Del Rosso, Rossana Norata, Martina Rocchi, Mila Della Barbera, Elena Rossi, Marco Cursi, Andrea Bergamaschi, Corrado Campochiaro, Giacomo De Luca, Marco Rasponi, Chiara Di Resta, Anna Palmisano, Paola Carrera, Luca Muzio, Alessandra Laura Giulia Pedrocchi, Letizia Leocani, Davide Lazzeroni, Francesca Sanvito, Simone Sala, Lorenzo Dagna, Paolo Guido Camici, Gianvito Martino, DeLisa Fairweather, Alida Linda Patrizia Caforio, Cristina Basso, Antonio Esposito, Leslie T Cooper, Paolo Della Bella\",\"doi\":\"10.1016/j.jacep.2025.02.025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The relationship between intercalated disc abnormalities (IDAs) and arrhythmias in inflammatory cardiomyopathy (ICM) remains incompletely understood.</p><p><strong>Objectives: </strong>This study presents a pilot research that aimed to: 1) investigate the link between IDAs and arrhythmias in humans with ICM; and 2) compare findings in humans and mice with experimental autoimmune myocarditis (EAM).</p><p><strong>Methods: </strong>Humans with ICM (N = 316) investigated for either genetic or autoimmune IDAs were identified at a referral center. Ultrastructural analysis on biobanked tissue was performed to determine the average intercellular cleft width (ICW) between cardiac myocytes. IDA+ cases were compared with IDA- control subjects matched 1:1 by age, sex, and race/ethnicity. The primary endpoint was the occurrence of clinically demanding supraventricular or ventricular arrhythmias, recorded either by Holter electrocardiography or implanted devices during a 24-month prospective follow-up. The relationships between ICW and arrhythmias were compared in humans and male mice with EAM (n = 12).</p><p><strong>Results: </strong>Of 316 humans with ICM (mean age 45 ± 15 years, 63% male), 70 (22%) were IDA+ and 107 (34%) had arrhythmias on admission. IDA+ patients had greater ICW than control subjects (44 ± 8 nm vs 28 ± 4 nm; P < 0.001) and higher incidence of clinically demanding arrhythmias both at presentation (31 of 70 vs 9 of 70; P < 0.001) and during follow-up (44 of 70 vs 10 of 70; P < 0.001). In a multivariable model, IDAs predicted the occurrence of major ventricular arrhythmias by 24 months (HR: 3.0; 95% CI: 1.4-6.4; P = 0.004). In mice, arrhythmias were documented in 7 of 12 EAM cases and 0 of 6 control animals (P = 0.038). Increased ICW was found in close relationship with arrhythmias in both species (humans: 32 of 44 with vs 4 of 52 without arrhythmias; P < 0.001; mice: 7 of 8 with vs 0 of 4 without arrhythmias; P = 0.010), as well as with abnormal ventricular electrograms on viable murine myocardial tissue (5 of 6 vs 0 of 6; P = 0.015).</p><p><strong>Conclusions: </strong>As a shared trait between genetic and autoimmune ICM, IDAs are linked to arrhythmias in humans and find promising applications in the EAM mouse model.</p>\",\"PeriodicalId\":14573,\"journal\":{\"name\":\"JACC. Clinical electrophysiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.0000,\"publicationDate\":\"2025-04-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACC. Clinical electrophysiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jacep.2025.02.025\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC. Clinical electrophysiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jacep.2025.02.025","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Intercalated Disc Abnormalities Are Linked to Arrhythmias in Inflammatory Cardiomyopathy.
Background: The relationship between intercalated disc abnormalities (IDAs) and arrhythmias in inflammatory cardiomyopathy (ICM) remains incompletely understood.
Objectives: This study presents a pilot research that aimed to: 1) investigate the link between IDAs and arrhythmias in humans with ICM; and 2) compare findings in humans and mice with experimental autoimmune myocarditis (EAM).
Methods: Humans with ICM (N = 316) investigated for either genetic or autoimmune IDAs were identified at a referral center. Ultrastructural analysis on biobanked tissue was performed to determine the average intercellular cleft width (ICW) between cardiac myocytes. IDA+ cases were compared with IDA- control subjects matched 1:1 by age, sex, and race/ethnicity. The primary endpoint was the occurrence of clinically demanding supraventricular or ventricular arrhythmias, recorded either by Holter electrocardiography or implanted devices during a 24-month prospective follow-up. The relationships between ICW and arrhythmias were compared in humans and male mice with EAM (n = 12).
Results: Of 316 humans with ICM (mean age 45 ± 15 years, 63% male), 70 (22%) were IDA+ and 107 (34%) had arrhythmias on admission. IDA+ patients had greater ICW than control subjects (44 ± 8 nm vs 28 ± 4 nm; P < 0.001) and higher incidence of clinically demanding arrhythmias both at presentation (31 of 70 vs 9 of 70; P < 0.001) and during follow-up (44 of 70 vs 10 of 70; P < 0.001). In a multivariable model, IDAs predicted the occurrence of major ventricular arrhythmias by 24 months (HR: 3.0; 95% CI: 1.4-6.4; P = 0.004). In mice, arrhythmias were documented in 7 of 12 EAM cases and 0 of 6 control animals (P = 0.038). Increased ICW was found in close relationship with arrhythmias in both species (humans: 32 of 44 with vs 4 of 52 without arrhythmias; P < 0.001; mice: 7 of 8 with vs 0 of 4 without arrhythmias; P = 0.010), as well as with abnormal ventricular electrograms on viable murine myocardial tissue (5 of 6 vs 0 of 6; P = 0.015).
Conclusions: As a shared trait between genetic and autoimmune ICM, IDAs are linked to arrhythmias in humans and find promising applications in the EAM mouse model.
期刊介绍：
JACC: Clinical Electrophysiology is one of a family of specialist journals launched by the renowned Journal of the American College of Cardiology (JACC). It encompasses all aspects of the epidemiology, pathogenesis, diagnosis and treatment of cardiac arrhythmias. Submissions of original research and state-of-the-art reviews from cardiology, cardiovascular surgery, neurology, outcomes research, and related fields are encouraged. Experimental and preclinical work that directly relates to diagnostic or therapeutic interventions are also encouraged. In general, case reports will not be considered for publication.
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