This week's episode features special Guest Host Mercedes Carnethon, as she interviews author Miriam Cortese-Krott and Associate Editor Charles Lowenstein as they discuss the article "Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure." 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-host I'm Dr. Carolyn Lam, associate editor from The National Heart Center in 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. Dr. Carolyn Lam: Greg, today's feature paper is one of those really, really landmark papers that really advance our understanding of Nitric oxide signaling. And it's about red blood cell and Endothelial eNOS, and how they independently regulate circulating nitric oxide, metabolites, and blood pressure. A real, real must, but let's go on and look at the other papers in this issue first. Greg, you want to go first? Dr. Greg Hundley: You bet, Carolyn. Better grab a cup of coffee. And my first paper is from professor Nathan Mewton from Hôpital Louis Pradel Hospices Civils de Lyon. Carolyn, these authors hypothesized that Colchicine a potent anti-inflammatory agent may reduce infarct size in left ventricular remodeling at the acute phase of STEMI. And so to address this hypothesis, they performed a double-blind multi-center trial and randomly assigned patients admitted for a first episode of STEMI referred for primary PTCA to receive oral Colchicine two-milligram loading dose followed by 0.5 milligrams twice a day, or matching placebo from admission to day five and the primary efficacy outcome was infarct size determined by cardiovascular magnetic resonance imaging at five days. And the relative left ventricular end-diastolic volume change at three months and infarct size at three months was also assessed by cardiac MRI. And these were secondary outcomes. Dr. Carolyn Lam: Nice. Okay. So what were the results? Dr. Greg Hundley: Right, Carolyn. So 192 patients were enrolled. 101 in the Colchicine group and 91 in the controls. And as a result of this trial, the oral administration of high dose Colchicine at the time of Reperfusion. And for five days thereafter did not reduce infarct size assessed by cardiac MRI. And so Carolyn, the clinical implications of these results suggest that other studies exploring the timing, pharma kinetics, and dose-response of Colchicine, as well as other anti-inflammatory agents are needed to identify an effective method to reduce infarct size and limit remodeling in this group of patients. Dr. Carolyn Lam: Wow, it's just such a rich field done with all this about Colchicine. Well, our next paper is a pre-specified sub-analysis of the randomized EAST-AFNET 4 Trial and the sub-analysis assess the effect of systematic early rhythm control therapy that is using Antiarrhythmic drugs or catheter ablation compared to usual care, which means allowing rhythm control therapy to improve symptoms in patients with heart failure. And this was defined in the sub-analysis as the presence of heart failure symptoms of New York Heart Association status two to three or a left ventricular ejection fraction of less than 50%. Dr. Carolyn Lam: Now, the authors led by Dr. Kirchhof at University Heart and Vascular Center UKE in Hamburg, Germany included 798 patients in this sub-analysis of whom 442 had HFpEF, 211 had heart failure with mid-range ejection fraction and 132 had HF-rEF over a median of 5.1 years of follow-up the composite primary outcome of cardiovascular death stroke or hospitalization for worsening heart failure, or for acute coronary syndrome occurred less often in patients randomized to early rhythm control therapy compared with patients randomized to usual care. And this was not altered by heart failure status with an interacti