The implication of chromosomal abnormalities in the surgical outcomes of Chinese pediatric patients with congenital heart disease.

Background: Copy 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. Methods: CNVs 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. Results: We 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). Conclusions: CNV 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.

Midterm Surgical Outcomes for ALCAPA Repair in Infants and Children.

BACKGROUND: Surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has been associated with excellent survival during recent years. The purpose of this study was to evaluate the effectiveness of reimplantation of the coronary artery and to investigate the recovery of postoperative cardiac and mitral valve (MV) function. METHODS: From 2005 to 2015, 80 patients who had ALCAPA received surgical correction. Among them, 49 were infants. The median patient age was 7.8 months. Operative strategies included reimplantation of the coronary artery in 71 patients, the Takeuchi procedure in another 7 patients, and coronary artery ligation in the remaining 2 patients. RESULTS: There were 11 hospital deaths and 2 late deaths. Six patients required intraoperative or postoperative mechanical circulatory support. A significant improvement in the ejection fraction (EF) and shortening fraction (SF) was present in all surviving patients at discharge, at a 3-month follow-up and at a 1-year follow-up. MV function improved gradually after surgical repair with no late secondary intervention. CONCLUSIONS: The repair of ALCAPA can be accomplished by establishment of a dual-coronary system, which offers an acceptable mortality rate and will rarely require a second surgery. Left ventricular (LV) recovery is a progressive process, especially for infants with impaired LV function. Concomitant MV annuloplasty is safe and reliable and can be performed as necessary in patients with moderate or severe mitral valve regurgitation.

Surgical and Transcatheter Treatments in Children with Congenital Aortic Stenosis.

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.

Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload.

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.

Surgical outcomes for anomalous left coronary artery from the pulmonary artery: Influence of late presentation.

OBJECTIVES: Although surgical outcomes for anomalous left coronary artery from the pulmonary artery (ALCAPA) are excellent in the modern era with the coronary reimplantantion technique, mortality remains high in Chinese population. This study was undertaken to review the surgical management for ALCAPA in our center and assess the midterm outcomes. METHODS: This was a retrospective review of 105 patients who underwent surgical repair for ALCAPA from January 2008 to January 2018. RESULTS: The diagnosis of ALCAPA was not made before referred to our hospital in 31 patients (30%). Median age at repair was 7.6 months (interquartile range, 4.3-25.4 months). Mean preoperative left ventricular ejection fraction was 47.3% ± 16.9%. Concomitant mitral intervention was performed in 52 patients (50%). Mechanical circulatory support was used in 15 patients (14%). Early mortality was 14%. Classification and regression tree analysis identified 3 risk groups for early mortality, among which patients with preoperative left ventricular ejection fraction ≤41.6% and age at repair >127 days were the most likely to suffer from mortality. Using nonlinear mixed-effect model to assess the time course for postoperative left ventricular ejection fraction, patients of this group also needed significantly longer time for recovery of left ventricular function after surgery (P < .0001). CONCLUSIONS: Late referral of patients with ALCAPA is not uncommon in our center. Older age at repair in patients with preoperative left ventricular dysfunction is the main reason for higher early mortality, and is also associated with longer time to normalization of left ventricular function after surgery.

[The left ventricular assistance device was used for anomalous origin of the left coronary artery from the pulmonary artery in perioperative period].

OBJECTIVE: To review the experience of left ventricular assistance device (LVAD) using for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in perioperative period. METHODS: There were 29 patients with ALCAPA underwent surgical repair from May 2006 to May 2013. The mean age was 6.5 months (ranging from 3.3 to 12.1 months). The mean weight was 6.2 kg (ranging from 4.1 to 9.5 kg). Diagnosis was established by echocardiography in all patients. There were clinical symptomatic of the severe heart dysfunction and ejection fraction were 23% to 45%. Mitral insufficiency was moderate to severe in 8 patients and less than moderate in others. Surgical methods included the intrapulmonary tunnel (Takeuchi procedure) of 4 cases, direct reimplantation of the left coronary artery onto the aorta of 6 cases and reimplantation by pericardiac patch enlarge of 19 cases. Valvuloplasty were performed in 5 patients with mitral severe insufficiency. Twenty-two patients were treated only by medicine therapy. LVAD was used in 7 patients: there were 3 patients with low blood pressure at the end of surgical repair and 4 patients with low cardio output within 24 hours postoperatively. RESULTS: Postoperatively, transesophageal echocardiography demonstrated that blood flow of the left coronary artery is fluently but left ventricular is also largement. The hemodynamic of 18 patients was stable in medicine group but 3 patients were sudden died of low cardiao output and ventricular fibrillation respectively. One patient was died of diffuse intravascular coagulation at the time of 72 hours after operation. The hemodynamic was stable in 6 patients in LVAD group and the devices after using time from 72 to 108 hours was taken down except one patient died of multi-organ dysfunction. The hospital mortality was 5/29 (17.2%). Nineteen survival (19/24) was followed up of 3.5 years (ranging from 1 to 7 years). Reoperations was performed for one patient with the supravalvar pulmonary stenosis due to the Takeuchi procedure 4 years postoperatively. Echocardiographic demonstrated that the blood flow of the left coronary artery are fluently. Mitral insufficiency was moderate in 2 cases, mild to moderate in 9 cases and mild in 8 cases. The ejection fraction value were 43% to 55% and apparent arrhythmia didn't occur. CONCLUSIONS: Although late results are satisfactory and left ventricular function always recovery, early mortality is higher even though the protective methods are carried out during the whole cardiopulmonary bypass procedure. In order to decrease the early mortality, heart function evaluation and LVAD should be used as an effective cardiac support technique to prevent heart failure in time.