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 a...
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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
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