This week's podcast features author Nicholas Mills and Guest Editor Allan Jaffe as they discuss the article "High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial." (https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052380) Dr. Carolyn Lam: Welcome to Circulation On The Run, your weekly podcast summary, and backstage pass to the journal and its editors. We're your co-hosts. 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 and VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, we're going to examine cardiac troponin, high-sensitive cardiac troponin, and its association with myocardial infarction. But first, before we get to that, how about we grab a cup of coffee and start in and review some of the other articles in the issue? Would you like to go first? Dr. Carolyn Lam: I would love that. The first paper brings up the problem of stroke, remaining a devastating complication of transcatheter aortic valve replacement or TAVR. Now, this stroke risk has persisted despite refinements and the technique and increased operator experience, while cerebral embolic protection devices have been developed to mitigate this risk data regarding their impact on stroke and other outcomes after TAVR are limited. Dr. Carolyn Lam: Dr. David Cohen from Cardiovascular Research Foundation in New York and colleagues performed an observational study using data from the STS-ACC TVT registry, including more than 123,000 patients from almost 600 sites who underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. Dr. Greg Hundley: Wow, Carolyn, this sounds like a really good use of the registry. What were the results? Dr. Carolyn Lam: Indeed, in this nationally representative observational study, the authors did not find an association between embolic protection device use for TAVR and in-hospital stroke in their primary instrumental variable analysis. And that's a technique designed to support causal inference from observational data with site-level preference for embolic protection device use within the same quarter of the procedure as the instrument. Dr. Carolyn Lam: However, they found a modestly lower risk of in-hospital stroke in their secondary propensity weighted analysis. These findings provide a strong basis for large-scale randomized control trials to really test whether embolic protection devices provide meaningful clinical benefit for patients undergoing TAVR. And this is discussed in a nice accompanying editorial by Dr. Tam and with Wijeysundera from University of Toronto. Dr. Greg Hundley: Very nice Carolyn. Well, my first paper comes to us from Professor Hua Zhang from Shanghai Children's Medical Center. Cyanotic congenital heart disease is a complex pathophysiological condition involving systemic chronic hypoxia and some cyanotic congenital heart disease patients are chronically hypoxic throughout their lives which heightens their risk of heart failure as they age. Dr. Greg Hundley: Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-Alpha. And Carolyn, this study aims to determine the effect of chronic hypoxia on cardiac metabolism and function in cyanotic congenital heart disease patients and its association with age. The authors investigated the role of hypoxia-inducible factor 1-Alpha in this process, and the potential therapeutic targets for this were explored. Dr. Carolyn Lam: What did they find Greg? Dr. Greg Hundley: In cyanotic congenital heart disease patients maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. In cardiomyocytes, specific HIF1-Alpha knockout mice, chronic hypoxia failed to initiate the switch of myocardial subs