RESUMEN
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.
Asunto(s)
Variaciones en el Número de Copia de ADN , Tetralogía de Fallot , Pueblo Asiatico/genética , Moléculas de Adhesión Celular/genética , ADN , Variaciones en el Número de Copia de ADN/genética , Proteínas Ligadas a GPI/genética , Estudio de Asociación del Genoma Completo , Humanos , Tetralogía de Fallot/genéticaRESUMEN
Objectives: The management of atrial isomerism with complex congenital heart disease remains challenging. Experience has been largely obtained in advanced countries. The clinical diversity is greater in China. We evaluated the early- and medium-term outcomes of surgical treatment of these patients. Methods: We reviewed 86 patients of atrial isomerism with complex congenital heart disease undergoing varied surgeries in our center in 2008-2020. Cox regression models were used to analyze the risk factors for mortality. Results: There were 75 cases of right and 11 of left atrial isomerism. Eighty-three (96.5%) patients underwent single-ventricle staged palliation approach, with 10 early and 7 late deaths. The overall 1-, 5-, and 10-year survival rates were 84.7, 79.3, and 79.3%, respectively. Thirty-six (43.4%) patients completed the Fontan procedure with median age of 48 months and freedom from death or Fontan failure at 1-, 5-, and 8-years were 94.4, 87.4, and 80.7%, respectively. Concomitant total anomalous pulmonary venous connection [hazard ratio (HR): 5.15 (1.95-12.94), p = 0.008], more than moderate atrioventricular valve regurgitation [HR: 4.82 (2.42-6.79), p = 0.003], and the need for first-stage palliative surgery [HR: 4.58 (1.64-10.76), p = 0.015] were independent risk factors for mortality. Conclusions: Despite even greater clinical diversity, the surgical outcomes of atrial isomerism with complex congenital heart disease are improving in China. The early and intermediate outcomes are comparable to many previous reports. Concomitant total anomalous pulmonary venous connection, moderate or severe atrioventricular valve regurgitation, and the need for a first-stage palliative surgery are still independent risk factors for mortality.
RESUMEN
OBJECTIVE: This study intends to summarize 5 years of intraoperative hybrid procedure (IHP) experience with neonates and young children having congenital heart disease (CHD). METHODS: From March 2003 to March 2009, a total of 152 consecutive patients younger than 2 years old who had undergone IHP were enrolled. In the balloon plasty group (n = 72), transventricular pulmonary valvuloplasty, or transaortic balloon dilatation were performed for pulmonary atresia, pulmonary stenosis, or coactation of the aorta. In the device group (n = 43), transventricular device closure was performed for ventricular septal defect (VSD), or transatrial device closure for atrial septal defect (ASD). In the collateral arteries occlusion group (n = 37), the major aortopulmonary collateral arteries (MPCAs) were occluded with coils for tetralogy of Fallot or other cyanotic CHDs. All procedures were image guided and performed in a specially designed hybrid operation room. All surviving patients were followed up, and the major adverse cardiovascular events that occurred were recorded. RESULTS: In the balloon plasty group, all patients received successful transventricular valvuloplasty or transaortic balloon angioplasty. However, severe right ventricle outflow obstruction was observed in 2 cases. One patient was transferred to regular open-heart surgery immediately, and another underwent regular open-heart procedure after discharge. Furthermore, 1 neonate with pulmonary atresia with intact ventricular septum died from liver failure 6 months after IHP. In the device closure group, the device closure failed to be performed in 3 cases (2 with ASD and 1 with VSD). One young child with VSD died from pneumonia, even after successful device closure. No device malposition was observed in the device closure group during follow-up. All patients who received MPCA occlusion and associated open-heart correction were eventually discharged. CONCLUSION: IHP could avoid or shorten the application of cardiopulmonary bypass and reduce surgical trauma for selected young children with CHD. Although IHP is feasible and safe, the image outfits, image-guided technology, and IHP-related devices should be developed and improved.