Background: Although heart failure is a well‐known major global public health concern, the general understanding of the clinical status of pediatric heart failure (PHF) is inadequate. Therefore, this study aims to enhance the general understanding of clinical characteristics across different PHF age groups and provide references for improving PHF treatment strategies. Methods: This multicenter retrospective cohort study involved patients from 20 Chinese provinces, primarily including hospitalized patients (aged ≤18 years) diagnosed with heart failure between January 2013 and December 2022. The study subjects were categorized into 4 groups: neonatal, infant and toddler, young children, and adolescent. Results: Herein, 2903 hospitalized patients with PHF were included. Significant differences were observed across age groups in clinical characteristics, auxiliary examination results, comorbid diagnoses, and hospitalization outcomes. After adjusting for covariates, the odds of in‐hospital death were significantly lower in the infant and toddler (odds ratio [OR], 0.46 [95% CI, 0.25–0.85]), young children (OR, 0.39 [95% CI, 0.18–0.85]), and adolescent (OR, 0.34 [95% CI, 0.13–0.87]) groups compared with the neonatal group. Furthermore, the odds of cardiovascular adverse events were significantly higher in the young children (OR, 1.91 [95% CI, 1.62–2.88]) and adolescent (OR, 2.16 [95% CI, 1.15–4.06]) groups compared with the neonatal group. Additionally, regarding the odds of a bad Ross class, the adolescent group had 1.85 times higher odds (95% CI, 1.11–3.09) compared with the neonatal group, 2.36 times (95% CI, 1.67–3.35) higher odds compared with the infant and toddler group, and 1.45 times (95% CI, 1.05–2.02) higher odds compared with the young children group ( P <0.05). Conclusions: This study emphasizes the importance of age‐specific stratification in PHF management, revealing distinct clinical and prognostic differences across various developmental stages. Registration: URL: https://www.chictr.org.cn . Unique identifier: ChiCTR2300078262.

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co‐factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS‐eGFP‐GST and NLS‐mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5‐decline‐related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP‐sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP‐q‐PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter −299 to −157 region. It was further verified that pcDNA3.1 (−)‐cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy‐related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway.

Left ventricle ejection fraction (LVEF) is still not well acknowledged in classification of pediatric heart failure (PHF). We categorized PHF according to LVEF and aimed to determine the role of LVEF in PHF classification. Patients who were diagnosed with HF were divided into three groups according to their LVEF values: HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The clinical information of PHF patients was compared among those three groups. Factors associated with HF with improved EF (HFimpEF) and risk factors for in‐hospital death in PHF patients were analyzed. A total number of 1228 cases were collected. The proportion of HF patients with preserved LVEF (66.3%) was significantly higher than those with mildly reduced LVEF (21.7%) and reduced LVEF (12%). Clinical features such as age, B‐type natriuretic peptide (BNP) level, Ross classification, and E/A abnormal proportion in HF children with different LVEF value were statistically different. HF patients with younger age, lower BNP levels, minor cardiac dysfunction and less E/A abnormality could be found with higher LVEF value. The proportion of primary disease in PHF was largely different in HFpEF, HFmrEF and HFrEF groups. Medication treatment was more aggressive in patients with lower LVEF, except for vasoactive drugs. Children with congenital heart disease in HFrEF group were more prone to develop into HFimpEF. Sepsis, renal insufficiency, and an abnormal E/A ratio are risk factors for in‐hospital death of HF children. Clinical features of PHF could be well classified by LVEF, which is an essential and helpful indicator for PHF classification and management.

Background: Pediatric heart failure (PHF) remains a major contributor to morbidity and mortality, yet standardized diagnostic and prognostic frameworks–particularly those leveraging left ventricular ejection fraction (LVEF)–are not well-established. This study evaluates clinical profiles, therapeutic interventions, and mortality outcomes across LVEF thresholds while identifying an optimal cutoff to refine risk stratification in PHF. Methods: This multicenter retrospective cohort study analyzed 1449 PHF patients (aged 1–18 years) across 30 tertiary centers (2013–2022). LVEF stratification employed conventional thresholds (50%, 55%) and an ROC-optimized cutoff (53%, derived via Youden index maximization). The primary outcome was in-hospital all-cause mortality. Multivariable logistic regression models, adjusted for clinical covariates, evaluated mortality predictors. The discriminative performance of LVEF thresholds was compared using area under the curve (AUC) analysis. Results: Distinct clinical profiles, etiologies, and treatments were observed across LVEF strata (50% vs. 55%; p < 0.05). A data-driven optimized LVEF threshold of 53% was identified for mortality prediction, demonstrating superior diagnostic accuracy with enhanced sensitivity and specificity across age groups. Multivariate analysis revealed LVEF ≥ 55% as protective (OR = 0.81, 95% CI: 0.68–0.96, p = 0.003), while ≥50% was non-significant (OR = 0.91, 95% CI: 0.74–1.12, p = 0.06). Elevated BNP (OR = 2.78, p < 0.001) and NT-proBNP (OR = 2.34, p < 0.001) strongly correlated with mortality risk. Age and sex showed no significant association with outcomes. Conclusion: In conclusion, an LVEF of 53% emerged as the optimal pediatric threshold for mortality prediction, outperforming conventional cutoffs of 50% and 55%. The integration of LVEF with biomarkers (BNP/NT-proBNP) provides a robust prognostic framework, underscoring the necessity for pediatric-specific LVEF criteria and multidimensional risk assessment in PHF management.

Cardiac remodeling in response to disease or tissue damage severely impairs heart function. Therefore, the description of the molecular mechanisms responsible is essential for the development of effective therapies. Trbp (Tarbp2) is a multifunctional RNA-binding protein that is essential during heart development, but its role in the adult heart and cardiac remodeling remains unknown. We generated inducible conditional knockout mice to delete Trbp from cardiomyocytes in young adults (Trbp-cKOs). While Trbp-cKO mice did not display a detectable phenotype, under stress conditions induced by transverse aortic constriction pressure overload, they rapidly developed severe heart failure; this was associated with maladaptive cardiac remodeling and increased interstitial fibrosis. RNA-sequencing revealed the induction of a fibrotic gene expression network and the TGF-β signaling pathway in Trbp-cKO hearts. In cultured neonatal rat ventricle cardiomyocytes (NRCMs), inhibition of Trbp resulted in an induction of the expression of both Tgfβ2 and Ltbp2; in contrast, Trbp overexpression repressed Tgfβ2 expression. Knockdown of Trbp in NRCMs that were co-cultured with neonatal rat cardiac fibroblasts (NRCFs) resulted in an increase in fibrotic gene expression. However, knockdown of Trbp in NRCMs combined with knockdown of Tgfβ2 in NRCFs using the same co-culture system failed to induce the same change in fibrotic gene expression. These data provide evidence for a critical role for Trbp in regulating cardiac fibrosis during cardiac remodeling mediated by cross-talk between cardiomyocytes and fibroblasts. The link to TGF-β signaling also highlights its importance and reveals a novel approach to intervention by targeting of Trbp.