Unlike single-gene mutations leading to Mendelian conditions, common human diseases are likely to be emergent phenomena arising from multilayer, multiscale, and highly interconnected interactions. Atrial and ventricular septal defects are the most common forms of cardiac congenital anomalies in humans. Atrial septal defects (ASD) show an open communication between the left and right atria postnatally, potentially resulting in serious hemodynamic consequences if untreated. A milder form of atrial septal defect, patent (PFO), exists in about one-quarter of the human population, strongly associated with ischaemic stroke and migraine. The anatomic liabilities and genetic and molecular basis of atrial septal defects remain unclear. Here, we advance our previous analysis of atrial septal variation through quantitative trait locus (QTL) mapping of an advanced intercross line (AIL) established between the inbred QSi5 and 129T2/SvEms mouse strains, that show extremes of septal phenotypes. Analysis resolved 37 unique septal QTL with high overlap between QTL for distinct septal traits and PFO as a binary trait. Whole genome sequencing of parental strains and filtering identified predicted functional variants, including in known human congenital heart disease genes. Transcriptome analysis of developing septa revealed downregulation of networks involving ribosome, nucleosome, mitochondrial, and extracellular matrix biosynthesis in the 129T2/SvEms strain, potentially reflecting an essential role for growth and cellular maturation in septal development. Analysis of variant architecture across different gene features, including enhancers and promoters, provided evidence for the involvement of non-coding as well as protein-coding variants. Our study provides the first high-resolution picture of genetic complexity and network liability underlying common congenital heart disease, with relevance to human ASD and PFO.
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http://dx.doi.org/10.7554/eLife.83606 | DOI Listing |
Diagnostics (Basel)
January 2025
Department of Radiology, Azienda Ospedaliero Universitaria, University of Cagliari, 09124 Cagliari, Italy.
Over the past decade, several trials and observational studies have validated the use of minimally invasive cardiac interventions as viable treatment options for various cardiac diseases. Transcatheter techniques for severe aortic valve stenosis have rapidly emerged as alternatives to surgical aortic valve replacement in certain patient populations. Additionally, non-surgical treatment options have expanded for conditions affecting other cardiac valves, such as the mitral valve.
View Article and Find Full Text PDFBMC Cardiovasc Disord
January 2025
Department of Cardiology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Yangpu District, Shanghai, 200433, China.
Background: Different left atrial appendage closure (LAAC) devices have been introduced into the clinical setting. A new dual-seal mechanism LACbes® occluder with isogenous barbs for LAAC has been designed to facilitate easier delivery and improve safety. The purpose of this study is to compare the clinical outcomes of the WATCHMAN with those of the LACbes® device for LAAC.
View Article and Find Full Text PDFEgypt Heart J
January 2025
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia.
Background: Precapillary pulmonary hypertension (PH) as complication in atrial septal defect (ASD) is closely related to right heart hemodynamics, such as right atrial pressure (RAP) and pulmonary vascular resistance (PVR). Right heart catheterization (RHC) as the gold standard for their measurement is invasive and not widely available in Indonesia. Electrocardiography (ECG) was proposed to be alternative in this matter.
View Article and Find Full Text PDFAnn Thorac Surg Short Rep
September 2024
Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota.
Transcatheter atrial septal defect closure is a prevalent minimally invasive treatment option but still has cerebrovascular accident (CVA) risk. An unusual thromboembolic CVA cause is device-related mechanical atrial injury. We describe the case of a patient with prior transcatheter atrial septal defect closure who had ongoing CVA despite anticoagulation.
View Article and Find Full Text PDFAnn Thorac Surg Short Rep
June 2024
Department of Cardiothoracic Surgery and Perfusion Services, The Heart Center, Nationwide Children's Hospital, Columbus, Ohio.
Background: Right ventricular (RV) failure after heart transplantation (HT) is common in those with pretransplantation elevated pulmonary vascular resistance (PVR). Mechanical circulatory support has been used as a bridge to recovery, with mixed outcomes. We describe a patient with failed single-ventricle palliation in whom severe RV failure developed after HT.
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