Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy : Single-cell multiomics

Kugo, Yosuke; Kawamura, Takuji; Harada, Akima; Tominaga, Yuji; Miki, Kenji; Ishida, Hidekazu; Ueno, Takayoshi; Miyagawa, Shigeru

doi:https://doi.org/10.1002/ehf2.15430

Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy : Single-cell multiomics

Kugo, Yosuke; Kawamura, Takuji; Harada, Akima et al.

ESC Heart Failure, 2025

アクセス数:45件（2025-12-06 01:32 集計）

固定URL: https://hdl.handle.net/11094/102973

閲覧可能ファイル

ファイル	フォーマット	利用条件	サイズ	閲覧回数	利用開始日	説明	information
ESCHeartFailure	pdf	なし	2.05 MB	27	2025.10.31

Creative Commons : 表示 - 非営利 - 改変禁止

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

タイトル	Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy : Single-cell multiomics
著者	ORCID 0000-0002-2774-4670 0000-0002-2774-4670 researchmap permalink yosukekugo yosukekugo Scopus Author ID 57199329352 57199329352 著者名 Kugo, Yosuke
	NRID 1000060839398 1000060839398 ORCID 0000-0003-2985-0036 0000-0003-2985-0036 researchmap permalink takuji-kawamura takuji-kawamura Scopus Author ID 55331768500 55331768500 著者名 Kawamura, Takuji
	NRID 1000070535426 1000070535426 著者名 Harada, Akima
	NRID 1000080838558 1000080838558 著者名 Tominaga, Yuji
	NRID 1000010772759 1000010772759 ORCID 0000-0001-7901-6133 0000-0001-7901-6133 researchmap permalink 7000015489 7000015489 Scopus Author ID 55361742100 55361742100 著者名 Miki, Kenji
	NRID 1000050467552 1000050467552 researchmap permalink researcher_cardio researcher_cardio Scopus Author ID 36863872000 36863872000 著者名 Ishida, Hidekazu
	NRID 1000060437316 1000060437316 researchmap permalink takayoshi-ueno takayoshi-ueno Scopus Author ID 8137931400 8137931400 著者名 Ueno, Takayoshi
	NRID 1000070544237 1000070544237 ORCID 0000-0003-0015-6569 0000-0003-0015-6569 researchmap permalink s-miyagawa3154 s-miyagawa3154 Scopus Author ID 55560624700 55560624700 著者名 Miyagawa, Shigeru
キーワード等	single-cell multiomics
	paediatric
	dilated cardiomyopathy
	left ventricular assist device
	bridge to recovery
	natriuretic peptides
	apoptosis
内容	Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy: Single-cell multiomics. ESC Heart Failure , ehf2.15430 (2025); https://doi.org/10.1002/ehf2.15430.
抄録	Aims: Paediatric heart transplantation requires lifelong immunosuppression, highlighting the need for recovery-oriented strategies. A subset of children with dilated cardiomyopathy (DCM) recovers left ventricular (LV) function after LV assist device (LVAD) implantation, allowing for device explantation. We aimed to identify factors associated with LV functional recovery using single-nucleus multiomics analysis of LV tissue collected at LVAD implantation. Methods: We included children with idiopathic DCM who underwent LVAD implantation between 2013 and 2023. Patients who achieved device explantation and medical stabilization were classified as the recovery group while those who required transplantation or died were classified as the non-recovery group. Single-nucleus RNA and ATAC sequencing were performed in six representative cases. Differential gene expression, chromatin accessibility and gene ontology (GO) enrichment analyses were conducted. Candidate markers were validated histologically and serologically in the full cohort. Results: Twenty-five cases were included (non-recovery, n = 15; recovery, n = 10). Age at LVAD implantation [median (range)] was 0.9 (0.1–4.6) versus 0.8 (0.3–5.6) years (P = 0.8), sex 27% versus 30% male (P > 0.9) and body weight 5.9 (3.8–14.0) versus 7.5 (5.0–26.0) kg (P = 0.049). LV ejection fraction at implantation was similar (24 (10–44) % vs. 15 (10–25) %, P = 0.2). RNA sequencing showed elevated NPPB, MYL7 and PCDH9 in recovery-group cardiomyocytes, with NPPB highest expression [baseMean = 16 305; log₂Fold Change (FC) = 2.698; P < 0.001] and an accessible chromatin peak at its locus (log₂FC = 1.17; P < 0.01). GO analysis indicated enrichment in apoptosis-related pathways (coefficient = 1.77, P = 0.023). Serum brain natriuretic peptide (BNP), the protein product of NPPB, was significantly higher in the recovery group at implantation [732 (372–4179) vs. 3048 (642–6032) pg/mL, P = 0.04] as was the proportion of non-apoptotic cardiomyocytes [0.21 (0.02–0.37) vs. 0.37 (0.19–0.48), P = 0.03]. Conclusions: Elevated NPPB expression and BNP levels at LVAD implantation are associated with LV recovery in paediatric DCM. These findings support an anti-apoptotic role of BNP in successful bridge-to-recovery outcomes.
出版者	Wiley
収録物名	ESC Heart Failure
刊行年月	2025-10-20
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102973
PISSN	20555822
eISSN	20555822
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/ehf2.15430
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
権利情報	© 2025 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	ESC Heart Failure. 2025
DC.title	Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy : Single-cell multiomics
DC.creator	Kugo, Yosuke
	Kawamura, Takuji
	Harada, Akima
	Tominaga, Yuji
	Miki, Kenji
	Ishida, Hidekazu
	Ueno, Takayoshi
	Miyagawa, Shigeru
DC.publisher	Wiley
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-10-20
DC.identifier	https://doi.org/10.1002/ehf2.15430
DC.subject	single-cell multiomics
	paediatric
	dilated cardiomyopathy
	left ventricular assist device
	bridge to recovery
	natriuretic peptides
	apoptosis
DC.description	Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy: Single-cell multiomics. ESC Heart Failure , ehf2.15430 (2025); https://doi.org/10.1002/ehf2.15430.
DCTERMS.abstract	Aims: Paediatric heart transplantation requires lifelong immunosuppression, highlighting the need for recovery-oriented strategies. A subset of children with dilated cardiomyopathy (DCM) recovers left ventricular (LV) function after LV assist device (LVAD) implantation, allowing for device explantation. We aimed to identify factors associated with LV functional recovery using single-nucleus multiomics analysis of LV tissue collected at LVAD implantation. Methods: We included children with idiopathic DCM who underwent LVAD implantation between 2013 and 2023. Patients who achieved device explantation and medical stabilization were classified as the recovery group while those who required transplantation or died were classified as the non-recovery group. Single-nucleus RNA and ATAC sequencing were performed in six representative cases. Differential gene expression, chromatin accessibility and gene ontology (GO) enrichment analyses were conducted. Candidate markers were validated histologically and serologically in the full cohort. Results: Twenty-five cases were included (non-recovery, n = 15; recovery, n = 10). Age at LVAD implantation [median (range)] was 0.9 (0.1–4.6) versus 0.8 (0.3–5.6) years (P = 0.8), sex 27% versus 30% male (P > 0.9) and body weight 5.9 (3.8–14.0) versus 7.5 (5.0–26.0) kg (P = 0.049). LV ejection fraction at implantation was similar (24 (10–44) % vs. 15 (10–25) %, P = 0.2). RNA sequencing showed elevated NPPB, MYL7 and PCDH9 in recovery-group cardiomyocytes, with NPPB highest expression [baseMean = 16 305; log₂Fold Change (FC) = 2.698; P < 0.001] and an accessible chromatin peak at its locus (log₂FC = 1.17; P < 0.01). GO analysis indicated enrichment in apoptosis-related pathways (coefficient = 1.77, P = 0.023). Serum brain natriuretic peptide (BNP), the protein product of NPPB, was significantly higher in the recovery group at implantation [732 (372–4179) vs. 3048 (642–6032) pg/mL, P = 0.04] as was the proportion of non-apoptotic cardiomyocytes [0.21 (0.02–0.37) vs. 0.37 (0.19–0.48), P = 0.03]. Conclusions: Elevated NPPB expression and BNP levels at LVAD implantation are associated with LV recovery in paediatric DCM. These findings support an anti-apoptotic role of BNP in successful bridge-to-recovery outcomes.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.rights	© 2025 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
DC.format	102973
citation_title	Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy : Single-cell multiomics
citation_author	Kugo, Yosuke
	Kawamura, Takuji
	Harada, Akima
	Tominaga, Yuji
	Miki, Kenji
	Ishida, Hidekazu
	Ueno, Takayoshi
	Miyagawa, Shigeru
citation_publisher	Wiley
citation_language	英語
citation_date	2025-10-20
citation_journal_title	ESC Heart Failure
citation_doi	https://doi.org/10.1002/ehf2.15430
citation_public_url	https://hdl.handle.net/11094/102973

Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy : Single-cell multiomics

閲覧可能ファイル

論文情報

論文詳細を表示