Please join author Ole Fröbert and Associate Editor Dharam Kumbhani as they discuss the article "Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial." 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 in Duke National University of Singapore. Dr. Greg Hundley: I'm Dr. Greg Hundley, associate editor, director of the Poly Heart Center at VCU health in Richmond, Virginia. Well, listeners, this week we've got a really hot feature topic pertaining to flu vaccines, which are coming in the US, North America, South America, coming up soon, and their relationship to myocardial infarction. But before we get to that feature discussion, let's grab a cup of coffee and jump in to some of the other articles in this issue. Oh, wait a minute. Our first article, we've got a co-author here. Carolyn, something about the VICTORIA trial, which you were a part of. Can you tell us a little bit about this? Dr. Carolyn Lam: I would love to, and first of all, I'm doing this on behalf of a big team, and I want to really, really call up first Dr. Paul Armstrong who's the senior author from University of Alberta. But let me tell you first about the VICTORIA study. VICTORIA evaluated vericiguat, a soluble guanylate cyclase stimulator, compared to placebo, in patients with heart failure with reduced ejection fraction with a recent worsening heart failure event and the primary result was actually a significant reduction in the primary composite outcome of cardiovascular death or heart failure hospitalization with vericiguat compared to placebo. Dr. Carolyn Lam: Now, interestingly though, in VICTORIA, we found that anemia occurred more often in patients treated with vericiguat at a rate of about 7.6% compared to placebo, which was 5.7%. Now, although earlier studies of another soluble guanylate cyclase stimulator like riociguat was found to be associated with anemia. The etiology really remains unknown. In the current paper, we explored the relationship between markers of anemia and vericiguat versus placebo in VICTORIA. We further explored the changes in hemoglobin and hematocrit over the course of the trial and their relationships with the primary composite outcome. Dr. Greg Hundley: Carolyn, this is such an important new study heart failure therapy for those with reduced ejection fraction, and again, an important topic related to anemia. What did they find? Dr. Carolyn Lam: Thanks, Greg. First, approximately a third of patients in VICTORIA had anemia at randomization, and this is using the standard sex-based definitions. With a lower hemoglobin indeed predicting a higher risk for cardiovascular death, heart failure hospitalization, all-cause mortality. As I had already mentioned, we found more anemia with vericiguat than with placebo. The interesting thing though is after 16 weeks, no further decline in hemoglobin occurred over the remaining and over 96 weeks of follow up, and the ratio of hemoglobin to hematocrit remained constant. Now, overall, the adverse event of anemia occurred in 7.1% of the patients. Dr. Carolyn Lam: Importantly, the lower hemoglobin was not related to the beneficial effect of vericiguat over placebo on the primary outcome. Now, I know all of that may be more descriptive and reassuring than really understanding the mechanism by which it occurred. Further mechanistic studies are certainly warranted to better understand the basis of the anemia development, and it's of principle importance because as you said, vericiguat I think it's going to be an important new medication that we can consider in high-risk patients with recent worsening heart failure with reduced ejection fraction. Dr. Greg Hundley: Thanks so much, Carolyn, especially the perspective of being an author on this particular study. Well, Car