For this week's Feature Discussion, join author author Hannah Valantine and Senior Associate Editor Biykem Bozkurt as they discuss the Original Research Article "Cell-Free DNA to Detect Heart Allograft Acute Rejection." TRANSCRIPT BELOW Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, I think we've got an interesting feature this week. Dr. Carolyn Lam: Oh boy, we sure do. This one is one of those potentially practice changing landmark papers. I'll give you a clue. It's about using cell-free DNA to detect heart allograft acute rejection in transplantation. Huge, huge, but you got to wait. Listen to the summaries of this week's exciting issue first. Greg, you want to go first? Dr. Greg Hundley: Yes. And I can't wait for that feature discussion. I think that's going to be one of our top papers this year, but first onto some of the summaries. So my first article comes to us from Dr. Pilar Alcaide from Tufts University School of Medicine. So Carolyn, despite the well-established association between T-cell mediated inflammation and non ischemic heart failure, the specific mechanisms triggering T-cell activation during the progression of heart failure and the antigens involved are poorly understood. So Carolyn, these authors hypothesize that myocardial oxidative stress induces the formation of isolevuglandin modified proteins that function as cardiac neoantigens to elicit CD4 positive T-cell receptor activation, and then promote heart failure. Dr. Carolyn Lam: Oh, that's really interesting. Inflammation in heart failure is a hot topic. Tell me more. Dr. Greg Hundley: So Carolyn, these authors discovered that TCR antigen recognition increases in the left ventricle as cardiac dysfunction progresses, and they identified a limited repertoire of activated CD4 positive T-cell chronotypes in the left ventricle. Mechanistically, cardiac pressure overload resulted in reactive oxygen species dependent dendritic cell accumulation of isolevuglandin protein adducts, which induced robust CD4 positive T-cell proliferation. Dr. Greg Hundley: So collectively, Carolyn, these results demonstrate an important role of reactive oxygen species induced formation of isolevuglandin modify cardiac neoantigens that lead to TCR dependent CD4 positive T-cell activation within the heart. And therefore, these results help understand the relationship between T-cell mediated inflammation and heart failure. Dr. Carolyn Lam: Wow. Super. Thanks, Greg. I'm moving all the way from basic science now to talk about intensive lifestyle interventions, which we know are first line approaches to effectively treat obesity and manage the associated cardio-metabolic risk factors. However, to date, whether effective lifestyle based obesity treatment in primary care works, we need more data. And this is what this paper provides. Dr. Carolyn Lam: This comes from Dr. Katzmarzyk and colleagues from Pennington Biomedical Research Center in Los Angeles. And what they report is the PROPEL Trial, which randomly allocated 18 clinics equally to usual care or an intensive lifestyle intervention, and subsequently enrolled 803 adults with obesity from participating clinics. The usual care group continued to receive their normal primary care, while the intensive lifestyle intervention group received 24 months of high intensity lifestyle-based obesity treatment in a program, embedded in the clinic setting and delivered by health coaches in weekly sessions initially and monthly sessions from months seven through 24. Dr. Greg Hundley: Well, Carolyn, sounds like a really practical study here. So what were these results? Dr. Carolyn Lam: Yes, Greg, this was a pragmatic tri