This week, please join author Mikael Dellborg and Associate Editor Gerald Greil as they discuss the article "Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age." Dr. Greg Hundley: Welcome listeners to this March 21st issue. And I am one of your co-hosts, Dr. Greg Hundley, Associate Editor Director of the Pauley Heart Center at VSU Health in Richmond, Virginia. Dr. Peder Myhre: And I am the other co-host, Dr. Peder Myhre, from Akershus University Hospital and University of Oslo in Norway. Dr. Greg Hundley: Well, Peder, we have a very interesting feature discussion this week. It focuses on adults with congenital heart disease. And as you are aware, over the last 25 to 30 years the survival rate of individuals with congenital heart disease has really improved. And this group, led by Professor Dellborg, will discuss with us more on results from a Swedish registry examining patients after the age of 18 with adult congenital heart disease. But before we get to that, how about we grab a cup of coffee and jump into some of the other articles in the issue? Would you like to go first? Dr. Peder Myhre: I would love it to, Greg, thank you. So Greg, the first paper is about aortic stenosis and the genome-wide association study looking at aortic stenosis in patients from the Million Veteran Program. And as you know, Greg, calcific aortic stenosis is the most common valve of heart disease in older adults and has no effective preventive therapies. Genome-wide Association studies, GWAS, can identify genes influencing disease and may help prioritize therapeutic targets for aortic stenosis. And in this study, which comes to us from co-corresponding authors, O'Donnell from VA Boston Health System and Dr. Natarajan from Massachusetts General Hospital, both in Boston Massachusetts, performed genetic analysis in 14,451 cases with aortic stenosis and almost 400,000 controls in the Multiancestry Million Veteran Program. And replication for these results was performed in five other cohorts. Dr. Greg Hundley: Wow, Peder, so a very large gene-wide association study. So what did they find? Dr. Peder Myhre: So Greg, the authors found 23 lead variants representing 17 unique genomic regions. And of the 23 lead variants, 14 were significant in replication, representing 11 unique genomic regions. And five replicated genomic regions were previously known risk loci for aortic stenosis, while six were novel. And of the 14 replicated lead variants, only two of these were also significant in atherosclerotic cardiovascular disease GWAS. And in Mendelian randomization, lipoprotein a and LDL cholesterol were both associated with aortic stenosis, but the association between LDL cholesterol and aortic stenosis was attenuated when adjusting for LP a. So Greg, in conclusion this study identified six novel genomic regions for aortic stenosis, and secondary analysis highlighted roles of lipid metabolism, inflammation, cellular senescence and adiposity in the pathobiology of or stenosis, and also clarified the shared and differential genetic architectures of aortic stenosis with atherosclerotic cardiovascular disease. Dr. Greg Hundley: Wow, Peder, what a beautiful description. Very comprehensive study. Well, my study comes to us from the world of preclinical science and, Peder, it involves embryonic heart development. So Peder, placental and embryonic heart development occur in parallel, and these organs have been proposed to exert reciprocal regulation during gestation. Poor presentation has been associated with congenital heart disease, an important cause of infant mortality. However, the mechanisms by which altered placental development can lead to congenital heart disease remain really unresolved. So in this study, led by Dr. Suchita Nadkarni from Queen Mary University of London and colleagues, the team used an in vivo neutrophil-driven placental inflammation model via antibody depletion of maternal circulating neutrophils a