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. 2024 Sep 18;4(5):oeae078.
doi: 10.1093/ehjopen/oeae078. eCollection 2024 Sep.

CTG repeat length underlying cardiac events and sudden death in myotonic dystrophy type 1

Hideki Itoh  1   2 , Takashi Hisamatsu  3 , Kazuhiko Segawa  4 , Toshiaki Takahashi  5 , Takumi Sato  6 , Hiroto Takada  7 , Satoshi Kuru  8 , Chizu Wada  9 , Mikiya Suzuki  10 , Takuhisa Tamura  10 , Shugo Suwazono  11 , Koichi Kimura  12 , Tsuyoshi Matsumura  13 , Masanori P Takahashi  14
Affiliations

CTG repeat length underlying cardiac events and sudden death in myotonic dystrophy type 1

Hideki Itoh et al. Eur Heart J Open. .

Abstract

Aims: Myotonic dystrophy Type 1 (DM1) is caused by the expansion of CTG repeats (CTGn) in the DM1 protein kinase (DMPK) gene, while it remains unclear whether CTGn may be associated with the incidence of cardiac events or sudden death in Japan as well as Europe. The aim of this study was to investigate the association between CTGn and cardiac involvements.

Methods and results: This cohort study included patients with DM1 who were retrospectively recruited from nine Japanese hospitals specializing in neuromuscular diseases. A total of 496 patients with DM1 who underwent a genetic test in the DMPK gene were analysed. Patients with congenital form or under 15 years old were excluded and patients were assigned into the quartiles. When we compared the incidence of cardiac events including advanced/complete atrioventricular block, pacemaker implantation, and ventricular tachycardias or mortality among four groups, patients with 1300 or longer CTGn experienced composite cardiac events [hazard ratio (HR): 3.19, 95% confidence interval (CI): 1.02-9.99, P = 0.014] more frequently and had significantly higher mortality rate (HR: 6.79, 95% CI: 2.05-22.49, P < 0.001) than those under 400 CTGn while the rate of sudden death was not significantly different.

Conclusion: Regarding the cardiac events and mortality in patients with DM1, patients with 1300 or longer CTGn are at especially high risk.

Keywords: Conduction disease; Myotonic dystrophy; Sudden death.

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Conflict of interest statement

Conflict of interest: None declared.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
PR and QRS intervals in each group corresponding to the CTG repeat length.
Figure 2
Figure 2
Cumulative event-free probabilities for composite cardiac events (A), all-cause mortality (B) and sudden death (C) among four groups depending on the underlying CTGn. DM1, myotonic dystrophy Type 1.
See this image and copyright information in PMC

References

    1. Harper PS. Myotonic Dystrophy. 3rd ed. London: Saunders; 2001.
    1. Ashizawa T, Gagnon C, Groh WJ, Gutmann L, Johnson NE, Meola G, Moxley R, Pandya S, Rogers MT, Simpson E, Angeard N, Bassez G, Berggren KN, Bhakta D, Bozzali M, Broderick A, Byrne JLB, Campbell C, Cup E, Day JW, De Mattia E, Duboc D, Duong T, Eichinger K, Ekstrom A-B, van Engelen B, Esparis B, Eymard B, Ferschl M, Gadalla SM, Gallais B, Goodglick T, Heatwole C, Hilbert J, Holland V, Kierkegaard M, Koopman WJ, Lane K, Maas D, Mankodi A, Mathews KD, Monckton DG, Moser D, Nazarian S, Nguyen L, Nopoulos P, Petty R, Phetteplace J, Puymirat J, Raman S, Richer L, Roma E, Sampson J, Sansone V, Schoser B, Sterling L, Statland J, Subramony SH, Tian C, Trujillo C, Tomaselli G, Turner C, Venance S, Verma A, White M, Winblad S. Consensus-based care recommendations for adults with myotonic dystrophy type 1. Neurol Clin Pract 2018;8:507–520. - PMC - PubMed
    1. Mahadevan MS, Yadava RS, Yu Q, Balijepalli S, Frenzel-McCardell CD, Bourne TD, Phillips LH. Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy. Nat Genet 2006;38:1066–1070. - PMC - PubMed
    1. Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M, Kino Y, Arandel L, Jollet A, Thibault C, Philipps M, Vicaire S, Jost B, Udd B, Day JW, Duboc D, Wahbi K, Matsumura T, Fujimura H, Mochizuki H, Deryckere F, Kimura T, Nukina N, Ishiura S, Lacroix V, Campan-Fournier A, Navratil V, Chautard E, Auboeuf D, Horie M, Imoto K, Lee K-Y, Swanson MS, de Munain AL, Inada S, Itoh H, Nakazawa K, Ashihara T, Wang E, Zimmer T, Furling D, Takahashi MP, Charlet-Berguerand N. Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy. Nat Commun 2016;7:11067. - PMC - PubMed
    1. Onkal R, Mattis JH, Fraser SP, Diss JK, Shao D, Okuse K, Djamgoz MBA. Alternative splicing of Nav1.5: an electrophysiological comparison of ‘neonatal’ and ‘adult’ isoforms and critical involvement of a lysine residue. J Cell Physiol 2008;216:716–726. - PubMed

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