The molecular atlas of postnatal mouse ventricular development has been made available and cardiac regeneration is documented to be a downregulated process. The right ventricle (RV) differs from the left ventricle. How volume overload (VO), a common pathologic state in children with congenital heart disease, affects the downregulated processes of the RV is currently unclear. We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 7 (P7) using a mouse model to induce a prepubertal RV VO. RNAseq analysis of RV (from postnatal day 14 to 21) demonstrated that angiogenesis was the most enriched gene ontology (GO) term in both the sham and VO groups. Regulation of the mitotic cell cycle was the second-most enriched GO term in the VO group but it was not in the list of enriched GO terms in the sham group. In addition, the number of Ki67-positive cardiomyocytes increased approximately 20-fold in the VO group compared to the sham group. The intensity of the vascular endothelial cells also changed dramatically over time in both groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the downregulated transcriptome revealed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway was replaced by the cell cycle in the top-20 enriched KEGG terms because of the VO. Angiogenesis was one of the primary downregulated processes in postnatal RV development, and the cell cycle was reactivated under the influence of VO. The mechanism underlying the effects we observed may be associated with the replacement of the PPAR-signaling pathway with the cell-cycle pathway.

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BackgroundCopy number variations (CNVs) have been shown to be overrepresented in children with congenital heart disease (CHD). Genetic evaluation of CHD is currently underperformed in China. We sought to determine the occurrence of CNVs in CNV regions with disease-causing potential among a large cohort of Chinese pediatric CHD patients and investigate whether these CNVs could be the important critical modifiers of surgical intervention.MethodsCNVs screenings were performed in 1,762 Chinese children who underwent at least one cardiac surgery. CNV status at over 200 CNV locus with disease-causing potential was analyzed with a high-throughput ligation-dependent probe amplification (HLPA) assay.ResultsWe found 378 out of 1,762 samples (21.45%) to have at least one CNV and 2.38% of them were carrying multiple CNVs. The detection rates of ppCNVs (pathogenic and likely pathogenic CNVs) were 9.19% (162/1,762), significantly higher than that of the healthy Han Chinese individuals from The Database of Genomic Variants archive (9.19% vs. 3.63%; P = 0.0012). CHD cases with ppCNVs had a significantly higher proportion of complex surgeries compared to CHD patients with no ppCNVs (62.35% vs. 37.63%, P < 0.001). Duration of cardiopulmonary bypass and aortic cross clamp procedures were significantly longer in CHD cases with ppCNVs (all P < 0.05), while no group differences were identified for complications of surgery and one-month mortality after surgery. The detection rate of ppCNVs in the atrioventricular septal defect (AVSD) subgroup was significantly higher than that in other subgroups (23.10% vs. 9.70%, P = 0.002).ConclusionsCNV burden is an important contributor to Chinese children with CHD. Our study demonstrated the robustness and diagnostic efficiency of HLPA method in the genetic screening of CNVs in CHD patients.

Background For patients with congenital aortic valve stenosis (AVS), comprehensive analysis of surgical aortic valvuloplasty (SAV) or balloon dilation (BD) is scarce and remains controversial. Methods This study reviewed AVS data (aortic peak gradient, aortic insufficiency, and survival and reoperation) for patients who were suitable for biventricular repair at our center in 2008 to 2018. Patients were categorized into two subgroups based on age (≤3 or >3 months). Results A total of 194 patients were treated, including 124 with SAV and 70 with BD. Resulting data revealed that residual aortic gradient at discharge was worse for BD (p = 0.001). While for patients younger than 3 months, the relief of AVS was comparable between the two groups (p = 0.624). There was no significant difference in time-related survival between the two groups (log-rank p = 0.644). Multivariate analysis demonstrated that preoperative left ventricular end-diastolic dimension predicted early death (p = 0.045). Survival in the two groups after 10 years was 96.8% in SAV and 95.7% in BD (p = 0.644). Freedom from reoperation after 10 years was 58.1% in SAV and 41.8% in BD patients (p = 0.01). There was no significant difference in freedom from reoperation between SAV and BD in patients younger than 3 months (p = 0.84). Multivariate analysis indicated that residual aortic peak gradient was predictive of reoperation (p = 0.038). Conclusion Both methods achieved excellent survival outcomes at our center. SAV achieved superior gradient reduction and minimized the necessity for reoperation. For patients younger than 3 months, BD rivaled SAV both in aortic stenosis relief and freedom from reoperation.