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. 2024 Dec 16;14(1):30469.
doi: 10.1038/s41598-024-77360-3.

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

Keiichi Hirono  1 , Yukiko Hata  2 , Shojiro Ichimata  2 , Naoki Nishida  2 , Teruhiko Imamura  3 , Yoshihiro Asano  4 , Yuki Kuramoto  5 , Kaori Tsuboi  6 , Shinya Takarada  6 , Mako Okabe  6 , Hideyuki Nakaoka  6 , Keijiro Ibuki  6 , Sayaka Ozawa  6 , Jun Muneuchi  7 , Kazushi Yasuda  8 , Kotaro Urayama  9 , Hideharu Oka  10 , Tomoyuki Miyamoto  11 , Kenji Baba  12 , Akio Kato  13 , Hirofumi Saiki  14 , Naoki Kuwabara  15 , Masako Harada  16 , Shiro Baba  17 , Mari Morikawa  18 , Hidenori Iwasaki  19 , Yuichiro Hirata  20 , Yuki Ito  21 , Heima Sakaguchi  21 , Susumu Urata  22 , Koichi Toda  23 , Emi Kittaka  24 , Seigo Okada  25 , Yohei Hasebe  26 , Shinsuke Hoshino  27 , Takanari Fujii  28 , Norie Mitsushita  29 , Masaki Nii  29 , Kayo Ogino  30 , Mitsuhiro Fujino  31 , Yoko Yoshida  32 , Yutaka Fukuda  33 , Satoru Iwashima  34 , Kiyohiro Takigiku  35 , Yasushi Sakata  36 , Ryo Inuzuka  37 , Jun Maeda  38 , Yasunobu Hayabuchi  39 , Tao Fujioka  40 , Hidemasa Namiki  41 , Shuhei Fujita  42 , Koichi Nishida  43 , Ayako Kuraoka  44 , Nobuhiko Kan  45 , Sachiko Kido  46 , Ken Watanabe  47 , Fukiko Ichida  48
Affiliations

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

Keiichi Hirono et al. Sci Rep. .

Abstract

Dilated cardiomyopathy (DCM) is a progressive myocardial disorder characterized by impaired cardiac contraction and ventricular dilation. However, some patients with DCM improve when experiencing left ventricular reverse remodeling (LVRR). Currently, the detailed association between genotypes and clinical outcomes, including LVRR, particularly among children, remains uncertain. Pediatric patients with DCM from multiple Japanese institutions recorded between 2014 and 2023 were enrolled. We identified their DCM-related genes and explored the association between gene variants and clinical outcomes, including LVRR. We included 123 pediatric patients (62 males; median age: 8 [1-51] months) and found 50 pathogenic variants in 45 (35.0%) of them. The most identified gene was MYH7 (14.0%), followed by RYR2 (12.0%) and TPM1 (8.0%). LVRR was achieved in 47.5% of these patients. The left ventricular ejection fraction remained unchanged (31.4% to 39.8%, P = 0.1913) in patients with sarcomere gene variants and in those with non-sarcomere gene variants (33.4% to 47.8%, P = 0.0522) but significantly increased in those without gene variants (33.6% to 54.1%, P < 0.0001). LVRR was not uniform across functional gene groups. Hence, an individualized gene-guided prediction approach may be adopted for children with DCM.

Keywords: Dilated cardiomyopathy; Genetics; Heart failure; Left ventricular reverse remodeling; Sarcomere gene.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Age distribution of the patients.
Fig. 2
Fig. 2
Comparison of serial echocardiographic data for the entire cohort and among patients according to variants. Left ventricular ejection fraction (LVEF) from baseline to follow-up for the entire cohort (A) and among patients according to variants: sarcomere gene variant (n = 7), non-sarcomere gene variant (n = 12), and negative variant (n = 22). (B) Left ventricular diastolic diameter (LVDD) Z-score from baseline to follow-up for the entire cohort (C) and among patients according to variants: sarcomere gene variant (n = 7), non-sarcomere gene variant (n = 12), and negative variant (n = 22) (D).
Fig. 3
Fig. 3
Genetic distribution of DCM. The genetic architecture of DCM spans 6 gene functions, as shown in the outermost colored text circle.
Fig. 4
Fig. 4
Left ventricular reverse remodeling rate. Left ventricular reverse remodeling rate at the last follow-up in variant-positive versus variant-negative patients with dilated cardiomyopathy (DCM) (A) and the functional gene group in variant-positive patients with DCM (B).
Fig. 5
Fig. 5
Kaplan–Meier analysis and time from diagnosis to life-threatening cardiac outcome. Event-free survival (A) and freedom from major adverse cardiac events (MACE) (B) in patients with dilated myocardiopathy (DCM). Event-free survival in patients with DCM (C) according to age (D) and plasma BNP levels. Kaplan–Meier curves were compared using the log-rank test.
See this image and copyright information in PMC

References

    1. Fatkin, D., Huttner, I. G., Kovacic, J. C., Seidman, J. G. & Seidman, C. E. Precision medicine in the management of dilated cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol74, 2921–2938. 10.1016/j.jacc.2019.10.011 (2019). - PubMed
    1. McKenna, W. J. & Judge, D. P. Epidemiology of the inherited cardiomyopathies. Nat Rev Cardiol18, 22–36. 10.1038/s41569-020-0428-2 (2021). - PubMed
    1. Mori, H. et al. CORRIGENDUM: Outcomes of dilated cardiomyopathy in japanese children - A retrospective cohort study. Circ J86, 916–917. 10.1253/circj.CJ-66-0204 (2022). - PubMed
    1. Lipshultz, S. E. et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med348, 1647–1655. 10.1056/NEJMoa021715 (2003). - PubMed
    1. Kirk, R. et al. The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. [Corrected]. J Heart Lung Transplant33, 888–909, 10.1016/j.healun.2014.06.002 (2014). - PubMed

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