Heart failure & cardiomyopathies
Role of NPPB for Recovery Post Ventricular Assist Device in Paediatric Dilated Cardiomyopathy: Single-Cell Multiomics
Authors' conclusion
Elevated NPPB expression and BNP levels at LVAD implantation are associated with LV recovery in paediatric DCM.
Study context
- Population
- Children with idiopathic dilated cardiomyopathy (DCM) undergoing LV assist device (LVAD) implantation, 2013–2023
- Participants
- 25 children
- Exposure
- Recovery vs non-recovery after LVAD implantation
- Recoveryn = 10
- Non-recoveryn = 15reference
- Outcome
- Factors associated with left ventricular (LV) functional recovery (single-nucleus multiomics of LV tissue at LVAD implantation)
- Follow-up
- LVAD implantation
Methodological detailssingle-nucleus multiomics (RNA and ATAC sequencing) in six representative cases, histological and serological validation in full cohort
- Single-nucleus multiomics (RNA and ATAC sequencing) in six representative cases
- Histological and serological validation in full cohort
Main finding
As reported in the abstract
Log2FC
2.698
P < 0.001
NPPB expression in cardiomyocytes (baseMean = 16 305)
Log2FC
1.17
P < 0.01
accessible chromatin peak at NPPB locus
Non-recovery
- Serum brain natriuretic peptide (BNP)
- 732 (372-4179) pg/mL
- Proportion of non-apoptotic cardiomyocytes
- 0.21 (0.02-0.37)
Recovery
- Serum BNP
- 3048 (642-6032) pg/mL
- Proportion of non-apoptotic cardiomyocytes
- 0.37 (0.19-0.48)
Serum brain natriuretic peptide (BNP)
Proportion of non-apoptotic cardiomyocytes
- Gene ontology (GO) enrichment in apoptosis-related pathways
- coefficient = 1.77, P = 0.023
Observational data: associations, not effects.
Further findings
Baseline characteristics at LVAD implantation (non-recovery vs recovery)
- Age, median (range), non-recovery vs recovery
- 0.9 (0.1-4.6) versus 0.8 (0.3-5.6) years (P = 0.8)
- Male sex, non-recovery vs recovery
- 27% versus 30% male (P > 0.9)
- Body weight, median (range), non-recovery vs recovery
- 5.9 (3.8-14.0) versus 7.5 (5.0-26.0) kg (P = 0.049)
- LVEF similar, median (range), non-recovery vs recovery
- 24 (10-44) % vs. 15 (10-25) %, P = 0.2
- Order as printed: non-recovery, n = 15; recovery, n = 10
Chromatin accessibility at NPPB locus (recovery-group cardiomyocytes)
- Accessible chromatin peak at NPPB locus
- log2FC = 1.17; P < 0.01
GO enrichment in apoptosis-related pathways
- Enrichment in apoptosis-related pathways
- coefficient = 1.77, P = 0.023
Serum BNP at implantation, median (range) · LVAD implantation
- Significantly higher in the recovery group
- 732 (372-4179) vs. 3048 (642-6032) pg/mL, P = 0.04
Proportion of non-apoptotic cardiomyocytes, median (range) · LVAD implantation
- Significantly higher in the recovery group
- 0.21 (0.02-0.37) vs. 0.37 (0.19-0.48), P = 0.03
Original publication
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