Podcasts about women's hospital

This episode features Dr. Hadine Joffe, Executive Director of the Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital & Paula A. Johnson Professor of Psychiatry in the Field of Women's Health at Harvard Medical School. Here, she discusses the Connors Center and more.

  This episode features Kirk Daffner, Wimberly Professor of Neurology at Harvard Medical School & Chief, Division of Cognitive and Behavioral Neurology at Brigham and Women's Hospital. Here he discusses the aging physician population, the risks they are facing around potential cognitive impairment or decline, the sensitivity of the issue, and more.

Dr. Jessica Kenison joins us to discuss re-balancing the immune system and introducing antigen-specific immune tolerance to treat T1D. Dr. Jessica Kennison is a Postdoctoral Research Fellow at Brigham and Women's Hospital and Scientist at AnTolRx, Inc. This episode is in our Ask the Expert style:  Ask the Expert is a ~30 minute digital cafe experience where scientists and grad students can meet and exchange with thought leaders in the field of type 1 diabetes. Link below to sign up for a seat in the cafe! https://thesugarscience.org/ask-the-expert/

At Christchurch Women's Hospital, when a support person stays with a new mum and baby -  they have to sleep on the floor.   Charity the Māia Health Foundation wants to change that - launching a campaign today to raise forty-four thousand dollars for comfy chairs you can sleep in. Lisa Kahu works in the mama and pēpi service in Kaikōura. She spoke to Corin Dann.  

At Christchurch Women's Hospital, when a support person stays with a new mum and baby -  they have to sleep on the floor.   Charity the Māia Health Foundation wants to change that - launching a campaign today to raise forty-four thousand dollars for comfy chairs you can sleep in. Lisa Kahu works in the mama and pēpi service in Kaikōura. She spoke to Corin Dann.  

This episode features Kirk Daffner, Wimberly Professor of Neurology at Harvard Medical School & Chief, Division of Cognitive and Behavioral Neurology at Brigham and Women's Hospital. Here he discusses the aging physician population, the risks they are facing around potential cognitive impairment or decline, the sensitivity of the issue, and more.

This week, your hosts Steve Lowry and Yvonne Godfrey interview Allison MacLellan of MacLellan Law Firm, P.C. (https://www.maclellanlawfirm.com/)   Remember to rate and review GTP in iTunes: Click Here To Rate and Review   Episode Details: Allison MacLellan of MacLellan Law Firm, P.C., the 2018 Massachusetts Lawyer of the Year, shares how she secured the largest verdict in Massachusetts history for an employment-related retaliation claim. The plaintiff -- a Haitian-American nurse named Gessy Toussaint, who worked at Brigham and Women's Hospital in Boston for over a decade -- sued the hospital and her nurse manager, Mary Ann Kenyon, for discrimination and retaliation, which began after Gessy defended a fellow Haitian-American nurse who was being verbally abused by management. In a true David-versus-Goliath-style trial, the hospital's large, powerful defense team attempted to tarnish Gessy's stellar career record with standard of care violations. Following 14 days of trial and three days of deliberation, a Suffolk County, Massachusetts jury awarded $28,213,000 in damages to Gessy for the retaliation she faced and cleared the hospital of any discrimination charges. Citing MacLellan's meritorious work as a solo trial lawyer, Judge Christine Roach issued an order for the defendants to pay attorney's fees and costs totaling $415,630.85.    Click Here to Read/Download the Complete Trial Documents   Guest Bio: Allison MacLellan Allison MacLellan is a litigator with proven results. In May 2018, Attorney MacLellan single-handedly secured the largest verdict in Massachusetts' history regarding a retaliation claim in the employment context after a two and a half week jury trial in Boston.   Attorney MacLellan was named a Massachusetts Lawyer of the Year in 2018 and has been recognized by her peers for her litigation skill and groundbreaking strides, which have changed the landscape of employment discrimination cases in Massachusetts. Ms. MacLellan has also been named a Massachusetts “Super Lawyer.”   Ms. MacLellan fights for her clients no matter how large the opponent and no matter the odds.  Read Full Bio Show Sponsors: Legal Technology Services - LTSatlanta.com Digital Law Marketing - DigitalLawMarketing.com Harris, Lowry, and Manton - hlmlawfirm.com   Free Resources: Stages Of A Jury Trial - Part 1  Stages Of A Jury Trial - Part 2

This week’s episode is special: we have the former and current Editors-in-Chief of Circulation on Circulation on the Run. Join Dr Amit Khera, Digital Strategies Editor of Circulation, as he speaks with Dr James T. Willerson, Editor-in-Chief from 1993 to 2004; Dr Joseph Loscalzo, Editor-in-Chief from 2004 to 2016; and Dr Joseph A. Hill, the current Editor-in-Chief. They will discuss the history of Circulation and how it continues to evolve. TRANSCRIPT Dr Amit Khera: Hi, this is Amit Khera. I'm digital strategies editor for Circulation from UT Southwestern Medical Center in Dallas. Today we have a very special Circulation on the Run. We have three Editors-in-Chief from Circulation. First, we have Dr James Willerson, who was the Editor-in-Chief from 1993 to 2004. He's a President Emeritus at the Texas Heart Institute. We also have Dr Joseph Loscalzo, who was Editor-in-Chief from 2004 to 2016, the Chairman of Department of Medicine from Brigham and Women's Hospital. And finally, Dr Joseph Hill, the current Editor-in-Chief, the Chief of Cardiology at UT Southwestern Medical Center. Welcome, gentlemen. Dr Joseph Hill: Thank you. Dr James Willerson: Thank you. Dr Joseph Loscalzo: Thank you. Dr Amit Khera: Dr Willerson, I must say, looking over the tenure prior to Dr Loscalzo, you had one of the longest tenures ever as Editor-in-Chief of Circulation, and certainly a lot happened in the practice of cardiology during that period. It was a really formative period in cardiology. As you think back, what were some of the most important topics that you covered during that time as Editor-in-Chief, thinking about the evolution of cardiovascular care and science at that time? Dr James Willerson: You have to remember, there have been many editors at Circulation. We all build on the shoulders of others, certainly I did. I really wanted Circulation to be the premier cardiovascular journal in the world. I wanted it to be much like the New England Journal of Medicine, but the New England Journal of Medicine Circulation of Cardiology. I wanted to publish it every week. We got permission to do that. That wasn't easy, but we were fortunate. I've been accused of wanting to publish it every day. There's actually some truth to that. I didn't make that. I didn't try very hard. I wanted to be able to present the information, important information, to everybody who cared about cardiovascular medicine: physicians, scientists, students, nurses, those who cared for people, and I wanted to do it frequently. I wanted to publish it quickly. So, we had some success with that. There are many other things that are well-known to the other editors, all of whom have built before me and after me, and I'm very proud of them. Dr Amit Khera: Well, thanks for that. And certainly, as you pointed out, this has been an evolution where you took the gauntlet, if you will, from the people before you, and then built on that and had many advances. I guess after you, Dr Loscalzo, you I think did have the longest tenure if I saw of any of the editors and similarly, a lot of evolutions in cardiovascular care and a lot in science, particularly during your time. Tell us a little bit about any particular papers or topics that you focused on, or that really were revolutionary in the cardiovascular space during your tenure. Dr Joseph Loscalzo: I'll pick up where Jim left off and just make the case that as you're suggesting, I mean, there's sort of been a natural transition of the kind of science that Circulation has been publishing over the tenure of the three editors here today. Before Dr Willerson, it was largely physiology and excellent clinical science. Jim really expanded the scope of what Circulation published to begin to put in press in its pages, fairly basic and translational science as well. I picked up from what he'd laid the groundwork for to expand the scope of that science. And as you know, expand it to the point that we had to develop daughter journals that would pick up the mantle in each of these increasingly subspecialized areas. So, it's hard to think about those papers that I found have the greatest impact because every field had several of them in my several years as editor. As you know, the subspecialty journals that we established, which remain active to the current time, are also broad in their scope from outcomes based research to genomics and proteomics insistence, cardiovascular medicine, to everything in between, imaging, intervention, heart failure, and electrophysiology to arrhythmias. Each of these was led, and continues to be led, by outstanding leaders in their subspecialty fields. I think the beauty of Circulation in contrast to even fine journals like the New England Journal of Medicine, is that Circulation has been able to put on its pages those studies that really do span quite a spectrum. We don't shy away from very basic studies. That actually began with Jim, I must say, because that wasn't the case previously. And of course, we move right through to epidemiology and outcomes based research. And the impacts have been broad in each of those fields, as witnessed by the excitement and uptake of the journal, measured however you wish, by impact factor, or citations, or the frequency with which it's referred to in the lay press. So, I think that tradition certainly continues under the current editor with papers of extraordinary impact. Dr Amit Khera: Thanks for that. I think your point about the evolution of science over time from Dr Willerson and certainly during your tenure and beyond to the breadth of Circulation currently. You also touched on the subspecialty journals. That happened in your watch and that was quite a marked change in cardiovascular medicine to have that explosion of new journals, if you will. What do you think the impact of those subspecialty journals has been for the cardiovascular field? Dr Joseph Loscalzo: We struggled with the idea about whether or not we should pursue that kind of fragmentation. What really pushed us was the fact that the acceptance rate remains quite low, in those days, probably eight or so percent range at its nadir. So, we were rejecting a lot of really excellent papers which wound up in competitor journal pages, that we would like to have accepted and been given the scrutiny of the careful reviews and editorials that accompany papers accepted by Circulation. We felt the best way to do that under the circumstances was to create these daughter journals. They succeeded, in many respects, beyond our wildest imagination. The numbers of papers that were published in the family increased, I think in the first two or three years, by at least 2-to 3000. So, that really speaks to the fact that we kept the best papers in the family. We gave them the right kind of audience. Some of these would have been too technical or too highly specialized to have been published in Circulation proper, but certainly of the highest quality and of significant relevance to the subspecialist. So, we think that it was a successful experiment. Now it's sort of become tradition. I think that the question that will always come up, of course, is can we fragment things more? I would say one of the best reasons to make the case that this was a successful experiment is that if imitation's the sincerest form of flattery, the New England Journal is now going to start three subspecialty journals. In fact, in my role now as an editor of the New England Journal, editor-at-large, they asked my input in how to design those daughter journals and what to expect from them. Dr Amit Khera: Well, I think that's a great point. It certainly has been a resounding success and as you pointed out, imitation is the best form of flattery. I'm going to pivot now to Joe Hill. Dr Hill, you have certainly been the beneficiary of all the great work that these two editors have done in the past. You've inherited a very successful journal and also have crafted your own vision for where you want Circulation to go in your mark. Tell us a little bit about some of the new initiatives you've tried to implement, leveraging on these past successes. Dr Joseph Hill: Thank you, Amit, it's an honor and a privilege to be in this conversation, frankly. I mean, Dr Willerson made this a weekly journal. That was back in the day when FedExes were flying around. Everything was paper. That kind of volume with that technology is impressive. And Dr Loscalzo, who has been a friend and mentor for many, many years, spearheaded the subspecialty journals, as we just heard, and took the journal to yet new heights. Each of you has been a pioneer and we've been fortunate to put together a team that I think has moved in exciting directions. We've leveraged technology now, such that we have our video conference meetings. We meet in a video conference with editors from 17 different countries. We have a third of our editors in Dallas, where I live, a third in the US outside of Dallas, and another third in 16 other countries. It turns out we alternate the time of that meeting each week because there's no single hour of the day that works around the globe, so we move it around to capture Asia or to capture California in alternating weeks. That has been a thrill and, honestly, I believe a robust success. We have leaders on the ground in all these different countries. We have a highly diverse team across the different subspecialty domains of cardiology, across different geographic regions, across race and sex and gender lines. It is an amazing team. And Amit, who leads our robust digital efforts, including this podcast and our efforts on social media, again, the opportunity now in the 21st century to take these initiatives forward has been a real privilege. Dr Amit Khera: It's ironic that Circulation was doing Zoom before everybody else was in the modern era. I'm going to pivot back to Dr Willerson. As Dr Hill just mentioned during your tenure how the volume of papers was handled, FedEx and sort of the nature of the journal publishing process. And now in the modern era, we have so much different information. We have a huge volume of journals. We have online, we have Twitter, we have podcasts. We have people that are consuming information in so many different ways. Tell us from your perspective, what's the role of the scientific journal currently and how has it changed at all in the last few decades? Dr James Willerson: It's always going to continue to evolve. It's about as good as it can be right now with Dr Loscalzo and Dr Hill's leadership, and I'm really proud of them. There'll be more. We can't even imagine what it will be in two or three years. Of course, it'll be better and better, faster, almost momentary. Thank you, Dr Hill. Dr Amit Khera: Thank you for that. I think we all look forward to seeing how this evolves more rapid information, rapid turnaround. I'm certain that will change. Dr Hill, you had a comment on that? Dr Joseph Hill: We live in an era now where peer review is under attack in many ways and pre-print journals, blogs and so forth. And one of the things that I've really seen, and we've all seen, is how the peer review process, and we're all authors, right, we live on the other end of that stick, but it really is important. It makes a big difference. And people who are anxious to accelerate that process, I totally get it. We work very hard to do that. At the same time we, following the traditions here, have an intentionally redundant review process where every paper is evaluated by multiple editors and multiple peer reviewers. On a number of occasions, we've avoided a pothole, or we've improved a paper many, many times. And that is something that has really been impressed on me that I think people who aren't on this side of the editorial fence might not appreciate as much. Dr Amit Khera: I think that's an important point about sort of the rigor about the way that articles come out in Circulation. And Dr Loscalzo, maybe as an extension of the last question, what do you see as some of the challenges going forward or opportunities for Circulation? You think about where it's been, but what are some of the things that you look forward to for Circulation in the future and what are some of the things you're concerned about? Dr Joseph Loscalzo: Well, I too am concerned about this issue of peer review being under attack, and I'm particularly concerned about it for papers that have direct clinical impact. A good example of that concern, of course, are papers published, or at least publicly released, on non-peer reviewed websites like the archive sites because of their importance in the COVID epidemic, potentially. We all know of cases of drugs, at least in test tubes, with cultured cells and viruses appear to be effective that have adverse clinical consequences. So that, and more than in any other sphere of science, ensuring that proper peer review from as many perspectives as possible is always a part of the process is absolutely critical for clinical medicine. And to me, the threat that this need for acceleration and rapid peer review poses and the sort of socialization of the transmission of scientific information that we're all interested in doing really has to have the brakes put on it a bit for the clinical science that the journal represents for this very important reason. Not to say we want to slow things down, we want to make sure that the best possible reviews are performed before we release it to the public. I know that, as Joe was pointing out, one of the most exciting parts of the role of when I led the journal was the weekly meeting. We had a face-to-face meeting because all of our associate editors, save one, was actually physically proximate and they could travel to our conference room. But it's a wonderful exercise to have people of very different perspectives, from basic scientists, to clinical electrophysiologists, to outcomes researchers, make comments on papers that were completely outside their sphere. The argument, of course, is if one can write and transmit a thought with the clear intent in a way that's rigorous and logical, that any reasonably bright person with reasonable scientific background should be able to understand it. And often these folks with very different scientific backgrounds have perspectives that very clearly improved the paper when they were acted upon. That's a process that doesn't exist in many other journals, I have to say. And I would encourage Joe, which I know, well, he's doing this because he enjoys it and he recognizes its importance, and Joe's successors continue to do that as well because that will ensure the value of the journal through all of the challenges that it is going to have to face in the next decade or two. Dr Amit Khera: I think that was a great point. We're certainly seeing candy bowl examples of the importance of this rigorous process of the editors looking through it carefully and, as you both mentioned, peer review. Joe Hill, I'm going to let you maybe have the last word. I know how hard the three of you have historically worked on your craft for the journal, how much effort you've put in, but I also know it's quite a rewarding job. What would you see as the best part of being Editor-in-Chief of Circulation? Dr Joseph Hill: Oh my, I'm learning something every day. I've been on about a steep a learning curve as when I was an intern at Dr Loscalzo's hospital long ago. Under Dr Willerson's term, I imagine many, many studies came in on acute coronary syndromes and thrombolytic therapy, primary PCI, antiarrhythmic drugs. We haven't seen an antiarrhythmic drug paper except for a recent review we did, but for quite a long time. It's artificial intelligence, it's big data, it's the UK Biobank, it's Omix, it's incredibly sophisticated genetics and genomics and basic science with genetic manipulations, IPS cells. It's a very different world now than it was 10 years ago, 20 years ago and it certainly will be again, 10 and 20 years down the road. We are now approaching, I will say, 600 COVID related papers, and they're still coming in at a record pace. The world has changed. As I said before, this is the 70th anniversary of this storied journal. And it is truly my honor to be able to stand on the shoulders of Doctors Loscalzo and Willerson. Dr Amit Khera: Thank you. I think that's a great way to end this podcast and congratulations on the 70th anniversary. It truly has been a privilege to chat with the three of you today. I want to thank you not only for what you've done for Circulation, but for the field of cardiovascular medicine. This is Amit Khera, digital strategies editor for Circulation. Next week we're back to our usual podcast with Carolyn Lam and Greg Hundley. Take care. Dr Greg Hundley: This program is copyright the American Heart Association, 2020.  

During Hour 3 of Felger and Massarotti, Mike and Tony continued to discuss the current events of the country and NASCAR’s banning of the Confederate flag.  Dr. Paul Sax, of Brigham and Women's Hospital, joined the show to talk about the latest in the Covid-19 pandemic.  Finally, the guys got into the latest in the NBA’s return.    

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its 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 associated editor from the Pauly Heart Center at VCU health in Richmond, Virginia. Well Carolyn, this week's feature investigates the compass trial and is going to examine the role of combination antiplatelet and anticoagulation therapy in patients with diabetes and cardiovascular disease. But before we get to that feature discussion, how about we grab a cup of coffee and jump in and discuss some of the other papers in the issue? Dr Carolyn Lam: You bet, Greg. I've got my coffee right here, and I'd like to start by talking about paclitaxel containing devices. You may already know this, but it was nice to revise that these significantly reduce re intervention in patients with symptomatic femoral, popliteal, peripheral artery disease, as we may expect. However, a recent aggregate data meta-analysis reported increase late mortality in pad patients treat it with these paclitaxel containing devices. Thus today's authors, Dr Rocha-Singh from Prairie Heart Institute of Illinois at St. John's hospital and their colleagues performed an individual patient data meta-analysis to evaluate mortality using data from eight randomized controlled trials of FDA approved paclitaxel coated devices using de identified data that was provided by manufacturers. Dr Greg Hundley: Well, Carolyn, what did they find? Dr Carolyn Lam: So in 2,185 patients and 386 deaths from eight paclitaxel coated device trials with a four year median follow-up, there was a 4.6% absolute risk of increased mortality associated with paclitaxel coated device use compared to balloon angioplasty at a median of four years follow up, significant loss to follow up and withdrawal rates of 24% and 23% in balloon angioplasty and paclitaxel cohorts respectively through five years were observed. Recovery of lost vital status data reduced the observed paclitaxel device associated mortality rate. And there was no paclitaxel drug dose mortality relationship identified. Dr Greg Hundley: Oh, Carolyn, I think this is really an important finding, and we have a nice editorial, don't we? So what was the take home message? Dr Carolyn Lam: Yeah. In fact, this was discussed in an important editorial by doctors Royce, Chakraborty and Dao from the USFDA. Now listen up. So based on the prior aggregate data meta-analysis and subsequent FDA review, FDA had already communicated that clinicians should consider the increased rate of long-term mortality when making treatment recommendations. They had also implemented updated labeling for this device class to communicate the risk. So in this editorial, the FDA commended the authors of the current individual patient data meta-analysis for providing important information towards signal refinement, and also commend at their collaboration with device manufacturers to work together with a shared goal of patient safety. Now, there are still many unanswered questions, including the mechanism for the observed increase in late term mortality associated with these devices and how the benefit risk profile of these devices may shift across various patient populations. Dr Greg Hundley: Well Carolyn, my paper comes from Professor Antje Beling from Charité – Universitätsmedizin Berlin in Berlin. And it investigates heart specific immune responses in an animal model of auto immune related Meyer carditis mitigated by an immuno proteasome inhibitor and a genetic ablation. So Carolyn, this study used mouse models to understand mechanisms involved in immune checkpoint inhibitor related Maya carditis, a phenomenon that we can observe in 5% to 10% of patients that are receiving these checkpoint inhibitors for treatment of their cancer. Dr Carolyn Lam: So what did they find, Greg? Dr Greg Hundley: Several things, Carolyn. All immuno proteasome deficient strains of mice showed mitigated auto-immune related cardiac pathology with less inflammation, lower pro-inflammatory and chemo tactic cytokines, less interleukin 17 production and reduced fibrosis formation. The auto-immune signature during experimental proponent I auto immune carditis with high immuno proteasome expression, immunoglobulin G deposition, interleukin 17 production in heart tissue, and troponin I directed humeral auto immune responses was also present in two cases of immune mediated related my carditis. Thus demonstrating the activation of heart specific autoimmune reactions by this checkpoint inhibitor related myocarditis therapy. So Carolyn, perhaps by reversing heart specific auto immune responses, immuno proteasome inhibitors applied to these mouse models demonstrated their potential to, in the future, aid in the management of auto-immune bio carditis in humans, possibly including cases with immune mediated myocarditis heart-related specific auto-immunity. Dr Carolyn Lam: Oh, that's really nice, Greg. Thanks. How about a quiz? Remember what desmoplakin is Greg? Dr Greg Hundley: I think this is going to do something with right ventricular cardiomyopathy. Dr Carolyn Lam: Very nice. Desmoplakin is the primary force transducer between cardiac desmosomes and intermediate filaments. And mutations in Desmoplakin indeed cause an arrhythmogenic form of cardiomyopathy that has been variably associated with arrhythmogenic right ventricular cardiomyopathy. Clinical correlates of desmoplakin cardiomyopathy have been limited to small case series. Today's paper, by Dr Helms from University of Michigan and colleagues is the largest series of desmoplakin mutation carriers reported to date. Dr Greg Hundley: So Carolyn, what did they find here? Dr Carolyn Lam: Among 107 patients with pathogenic desmoplakin mutations and 81 patients with pathogenic Plakophilin-2 mutations as a comparison cohort, they found compelling evidence that desmoplakin cardiomyopathy is a distinct form of cardiomyopathy marked by a high proclivity for left ventricular hypertrophy and arrhythmias and associated with intermittent myocardial inflammatory episodes that appear clinically similar to myocarditis or sarcoidosis. Furthermore they found that diagnostic and risk stratification variables that performed well for Plakophilin-2 associated ARVC exhibited poor accuracy for the diagnosis and risk assessment of desmoplakin mutation carriers. So these results strongly indicate that a genotype specific management approach is essential for desmoplakin cardiomyopathy. Dr Greg Hundley: Wow, Carolyn. Lots of great science in this issue. Well, just like last week, we have got a lot of other papers in this issue. So let me tell you about a few that I've had a chance to preview. The first is a research letter by our own Dr Hesham Sadek from UT Southwestern Medical Center involving the homotypic fusion generates multi nucleated cardiomyocytes in the murine heart. Next is an ECG challenge. It's from Dr G. Neil Kay at the University of Alabama at Birmingham, and really reviews an ECG in a patient that presents with pulmonary embolism. Next, there's a case series from Dr Nil Uriel from Columbia University Medical Center regarding the variety of cardiovascular presentations of COVID-19. Next there's an on my mind piece that comes to us from Dr Ersilia DeFilippis from Columbia University College of and Physicians and Surgeons. And it involves cardiopulmonary resuscitation during this COVID-19 pandemic. And it presents a view from trainees on the front lines. Next, Carolyn, one of your faves, Dr Leslie Cooper from the Mayo Clinic provides an informative white paper on the description and proposed management of acute COVID-19 cardiovascular syndromes. Next is a paper from Dr Francine Marquez from Monash University, and it's a perspective piece on the impact, strategies and opportunities for early and mid-career cardiovascular researchers during the COVID-19 pandemic. So many studies have been stopped and this very nice article highlights the new opportunities in this pandemic. Next, Dr Anabel Volgman from Rush University Medical Center has a piece on the seniors on the sidelines, and it's a call to action. And then finally, Dr Andrew Chapman from University of Edinburgh and professor Christian Mueller from the University Hospital of Basel exchange letters to the editor regarding a prior article of high sensitivity cardiac troponin, and the universal definition of myocardial infarction. Dr Carolyn Lam: Nice. There's also a research letter by Dr Sandoval and colleagues who described the transition to using high sensitivity troponin T in a United States regional healthcare system, namely the Mayo Clinic enterprise. And they really showed that a small increase in MI diagnosis in part due to an increase in type two MI diagnosis occurred without an overall increase in hospital admissions or resource utilization using the high sensitivity cardiac troponin T implementation. And if I may mention, there is also a beautiful white paper by Dr Sana Al-Khatib, whom I was very lucky to coauthor with. And it's on the advancing research on the complex interrelations between atrial fibrillation and heart failure. This a report from the National Heart Lung and Blood Institute virtual workshop. Wow. A bonanza of an issue. Thanks so much, Greg. Let's move on to our feature discussion now. Dr Greg Hundley: Look forward to it. Dr Carolyn Lam: Today's feature discussion was in fact a late breaking clinical trial presentation at the American College of Cardiology meeting this year, 2020. And it's all about the compass trial, this time focusing on diabetes. I'm so, so pleased to have with us, the corresponding author Dr Deepak Bhatt from Brigham and Women's Hospital, as well as Dr Gregory Lip from University of Liverpool who was not only the guest editor, but also an editorialist for this paper. So welcome gentlemen. Deepak, could I start with you? This was an incredible presentation that was very well discussed. ACC not virtually, but I'm just so glad that we can have you on this podcast to tell us again, please, the rationale, the key findings and why this paper is just so important. Dr Deepak Bhatt: So the background really is that prior studies and particular registry studies, the reach registry, for example, have shown that patients with concomitant CAD and/or PAD, that is coronary artery disease and/or peripheral artery disease, plus diabetes, are folks that are extremely high risk of future ischemic events. This is true even if they are apparently stable outpatients. At any rate in the compass trial, these sorts of patients with CAD or PAD, stable patients, both with and without diabetes who are enrolled 27,000 plus patients randomized. And there were three arms in this study, aspirin alone, rivaroxaban alone and aspirin plus low dose rivaroxaban 2.5 milligrams twice a day. And that was the winner, that combination sometimes referred to as dual pathway inhibition significantly reduced the schemic events versus aspirin alone, a significant reduction in cardiovascular death MI stroke, as well a lower rate significantly so of cardiovascular death, and even all-cause mortality was lower. So the overall trial was positive, but what we wanted to examine in this analysis was specifically how to patients with diabetes fare, knowing that they're a higher risk group in general across multiple registries and studies? And indeed we found that they were higher risk, those with diabetes versus those without diabetes and compass, and indeed, though their relative risk reductions were similar, those patients with diabetes had numerically larger, absolute risk reductions than those without diabetes with this regimen of low dose rivaroxaban plus aspirin versus aspirin alone. Dr Carolyn Lam: Thanks Deepak. And I just have to refer the listeners to those beautiful figures in your paper. I mean, just one look at it really explains exactly what you were saying and really highlights that patients with diabetes are at higher risk of adverse events and also in one of the graphs of bleeding. Greg, could I bring you in here? You mentioned that in your editorial as well, that there has to be importantly acceptable bleeding risks. Could you expand on that? Dr Gregory Lip: The compass crowd was a game changer and in this high-risk subgroup, as Deepak elegantly has described. These are diabetic patients, and then we also have the subgroups we call with or without PCI. And those would be so of course, being the higher risk group of patients. Nonetheless, the comparison was basically a dual pathway inhibition, but a combination rivaroxaban plus aspirin compared to aspirin alone. But a high cardiovascular risk and high bleeding risk tend to track each other. So it was important that we certainly want to reduce the adverse outcomes of cardiovascular endpoints, we should certainly individualize our assessment of our patients and make sure that a patient is not an excessive high bleeding risk. I think overall, the study is very reassuring because there was no significant access in the overall population of the subgroup, at least in relation to fatal bleeding, critical organ bleeding or intracranial hemorrhage by dual path inhibition. But I think we, as physicians, just need to assess the patient in front of us just to make sure that particular patient is not at high risk particularly of bleeding, given that high risk of bleeding also generally is high cardiovascular risk as well. Dr Carolyn Lam: Thank you, Greg. And Deepak, perhaps maybe some words from you about this sort of risk benefit ratio? How do you see it? How do we apply these results? Dr Deepak Bhatt: I totally agree with everything Dr Lip said. Really, the key message when we're talking about antithrombotic numbers, something Dr Brunwald had said in this context, that is, there's no free lunch. When it comes to antithrombotics, there's always bleeding risks. There's just no way around that. In any trial that is adequately powered long enough, we'll find that, and that can include bad bleeding. Now, fortunately there was no significant excess and failure endocranial bleeding within the trial or within the subgroup of patients with diabetes. But nonetheless one needs to be cautious because these of course are carefully selected patients at low bleeding risk to get into the trial. There was a run in period. So when applying to real life, of course, there's the potential for bleeding. So we need to be really cautious about that. And it's also not a stat. So if we were talking about secondary prevention, either with or without diabetes, CAD, PAD, both of them together, of course, all those patients should be on Statin assuming they don't have a real type of contraindication. So that's kind of a no brainer. That's a matter of implementation science. A lot of patients that should be on Statin aren't, but that's not an issue of science. We already know the answer there. Here, it's not the case of everyone that is like this who has diabetes, or even who doesn't, who has CAD or PAD should be on this regimen. It needs to be carefully selected patients, patients that are a low bleeding risk. And sometimes doctors ask, "Well, how do you tell that?" Well, it's not always easy, but for sure there's some things that predict future bleeding risks such as prior bleeding. So prior bleeding, anemia, those are powerful predictors of future bleeding. And one would want to be really cautious in these largely stable outpatients that we're talking about in the compass trial in intensifying their antithrombotic regimen. But in the right patients, I think it's a really effective way of reducing important future vascular risk, whether that's cardiovascular risk consisting of MI related end points, stroke, peripheral ischemic end points, including amputation, which was significantly reduced in the trial, and within the subgroup of those with diabetes. So it's a matter of balancing those, but I do think with careful decision-making on the part of the physician, with discussion with the patient, with their understanding of the risks and benefits of intensifying the antithrombotic regimen beyond aspirin, there are a substantial number of patients who could benefit. Dr Gregory Lip: I whole fully agree with Deepak's comments. And we do have to bear in mind also that risk is also a fairly dynamic process and we may well be assessing the patient as the one off initially while we are initiating treatment. But of course risk, whether from cardiovascular risk or whether from bleeding risk particularly, also is influenced by increasing age and by incident comorbidities, which really means that risk reassessment should be performed in every patient we contact. With bleeding risks in particular, there are modifiable bleeding risk factors that we can mitigate. So proactive assessment or rather reassessment of risks, whether both from cardiovascular events and/or bleeding, is necessary as we follow up these patients. Dr Carolyn Lam: Thank you, both. Deepak, I'm just going to build a bit on your analogy of no free lunch. And maybe sort of a general question do you both, because it seems like we've got a bonanza of a buffet now when it comes to diabetes, especially with the new anti-diabetic drugs. So how do you think this fits in altogether? You talked about Statins. We now talk about low dose rivaroxaban in addition to aspirin, and you think diabetic patients should be treated with all? Maybe Deepak first, then Greg. Dr Deepak Bhatt: What a terrific question. In fact, that was asked of me by the late-breaking clinical-trial panel clinical trial panel. They said, "Well, how does it fit in? Because these data look terrific, but there's also other new diabetes drugs and approaches." So for sure, I would say again, barring a real contraindication, I would say everyone that we're talking about here should be on a statin and preferably if they can tolerate it, a high intensity statin. And if that doesn't do the trick in terms of LDL goal, I would say zetomyde. And potentially if they're in a region of the world where it's affordable a PCSK9 inhibitor. Then beyond that, I think we've got to pay attention to triglycerides these days, not just LDL cholesterol and if it's some patient that's sort of like REDUCE IT, well then, they should be on eicosapentaenoic. So we can modify LDL related and triglyceride related risks without too much effort or too much in the way of side effects. Then beyond that, I would say, we've got to think about blood pressure, inadequate control, especially in those with diabetes, but even those without that have cardiovascular disease. And then we have to think about glycemic control. And I don't mean the old-fashioned way, but I mean with some of the newer drugs. SGLT2 inhibitors in particular have been found to be useful for both. That's just the glycemia control part of things, more importantly, cardiovascular outcomes. In particular, heart failure and renal related outcomes. And then GLP 1 agonist as well have been shown to be very useful once more modifying cardiovascular outcomes, including atherosclerotic outcomes. So there is, as you say, quite the buffet. And assuming a patient can tolerate that polypharmacy and afford it, I do think the majority of patients with diabetes should be treated that well. And that's of course on top of lifestyle modification, weight loss is particularly important, plant-based diet, et cetera. But on top of that, then, with all those things that are being done and a patient is still at high ischemic risk but is at low bleeding risk, that's where I think, even in the deceptively stable appearing outpatient, it's worthwhile just running a mental checklist and saying, "Okay, are they on an SGLT2 inhibitor? Check. Did In someone measured their triglycerides? Check." And then on that checklist is, "Yeah, could they tolerate being on more than just aspirin alone in terms of bleeding risk? And if the answer to that is yes, might they benefit from adding this on?" And there are a lot of patients these results apply to, and I think a proportion of those patients who are otherwise optimally treated for their risk factors are the ones to target. Dr Carolyn Lam: Beautifully put. And Greg? Dr Gregory Lip: Deepak does raise an increasingly applied concept in how we approach our patients at high risk of cardiovascular events. That's the so called integrated or holistic approach to management. Because we have in the past tended to just focus on one strand of management. For example, we may well just be putting a lot of focus when on the analytic reduction and ignoring the rest. Well, we can't do that these days. We have to manage the whole patient and not just the bit of the patient. And this brings in this holistic approach, this integrated approach. And I think Deepak summarized that very nicely. It may require a number of medical approaches or medication-based approaches, but we have to practically look at the comorbidities like blood pressure reduction and also the lifestyle changes that Deepak's already summarized. So a holistic and integrated approach to our care of these patients. And in fact, some of the more recent studies showed nicely how this results in better outcomes in our patients at high cardiovascular risk. Dr Carolyn Lam: And in fact, those were exactly the last words of your editorial. A holistic and integrated care approach. Beautifully done, thank you both so much for this excellent discussion. Thank you, audience, for joining us today. You've been listening to Circulation on the Run. Don't forget to tune in again. Next week. Dr Greg Hundley: This program is copyright the American Heart Association 2020.  

Upstatement officially opened its doors in 2008 but was born during late nights at the Syracuse University student newspaper. That's where founders Mike, Jared, and Tito met before graduating to the newsrooms of The New York Times and Boston Globe. But they don't come from a typical agency background, and Upstatement doesn't look like your typical studio. Their team is filled with curious, versatile designers and engineers who all do a little bit of everything: Designers develop. Engineers sketch. Everyone contributes to creative concepts (because the best work comes from diverse teams). That's why nothing they do is cookie cutter. It's much more about daring to dream big, looking for fresh challenges, and push themselves. Here in 2020, the company provides design leadership for a diverse client list: publishers, products, non-profits, and the world's most remarkable brands. All unified by strong stories and the desire to make a positive impact. Tito Bottitta joins me on Tech Talks Daily to talk about how Upstatement is connecting with doctors on the front lines of the coronavirus pandemic to build the COVID Protocols product. Tito shares how they are helping the team of over 50 Brigham and Women's Hospital physicians, respiratory therapists, pharmacists, and nurses from multiple different divisions, organize the vast amounts of incoming info, and decide next how best to share it. From a technology perspective, I learn how Upstatement is building something useful around obstacles like hospital firewalls, etc. We also discuss what it's like designing quality work under extreme pressure (time & safety). The latest iteration, viewable at covidprotocols.org, came together thanks to Dr. Lee and Boston-based digital design and engineering studio, Upstatement. Through the partnership, Upstatement rapidly worked to find user base value in the tool while keeping it as a Google Doc by rebuilding potential caching problems that sending tens of thousands of people into a file at once could pose - making them a major key player in the project's success. The tool also had to be something useful built around obstacles like hospital firewalls, etc. Tito shares their inspirational work across three projects that are leveraging technology to create a unique approach to making a difference against the global pandemic. COVID Protocols - Captures emergent medical conventions that help doctors make life-saving decisions on the front lines. In association with Brigham & Women's Hospital. Read more about it on Medium. COVID Safe Paths - A privacy-first contact tracing app that could help us flatten the curve and return to normal. In association with MIT, Path Check Inc., and others. Read more about it on Medium. Project Z - Think of it as Yelp for COVID safety. Find the local businesses that are doing the most to keep you safe. When you have to go out, do it with confidence. In association with a group of silicon valley founders & V.C.s.  

Nurses held a silent protest outside Brigham and Women's Hospital to show solidarity to those protesting the death of George Floyd. WBZ NewsRadio's James Rojas reports.

Nurses held a silent protest outside Brigham and Women's Hospital to show solidarity to those protesting the death of George Floyd. WBZ NewsRadio's James Rojas reports.

A group of nurses held a silent protest outside of Brigham and Women's Hospital to show support for those protesting the death of George Floyd. WBZ NewsRadio's James Rojas reports.

In episode 31, we talk to Dr. Heather Hirsch about the opening of the Menopause & Midlife Clinic, Brigham and Women's Hospital at Harvard Medical Center.  She is changing the way midlife women experience menopause, perimenopause, chronic illness, breast cancer and other midlife issues.  At the clinic, proper time is given to patients in order to educate women and give them the information they need to make the right menopausal decisions for themselves.  She is also teaching the next generation of doctors to understand this normal stage of life.  Dr Hirsch has a great deal of information on her website and her podcast.https://www.heatherhirschmd.comhttp://hotflashescooltopics.comhttps://www.facebook.com/groups/657557054765087/  

Dr. Marshall, with Brigham and Women's Hospital, talks with Scott about an opportunity for those over 50 to take part in a study of Alzheimer's Disease.  

As communities around the world search for solutions to COVID-19, Tito Bottitta '03, Jared Novack '06 and Mike Swartz '06 are using their company, Upstatement, to design three initiatives to contain the spread of this disease. Collaborating with doctors at Brigham & Women's Hospital, COVID Protocols created guidelines for treating COVID-19 patients. COVID Safe Paths is a contact tracing app that allows people to find out if they've been exposed to the disease while mapping out a digital record of infection locations for public health officials. Project Zero identifies what precautions businesses are taking to keep their customers safe during the pandemic. The three discuss the impact these groundbreaking initiatives are having in the fight against the coronavirus, share how their time at Syracuse University and The Daily Orange led to the formation of Upstatement, and much more!

In this episode, host Chelsey talks all things related to NMO pain with Dr. Shamik Bhattacharyya, a neurologist at Brigham and Women's Hospital and assistant professor of neurology at Harvard Medical School. Chelsey learns that pain is very prevalent in NMOSD, and presents itself in many ways. They chat a bit about the science of NMO-related pain, exploring how and why it's different than pain related to multiple sclerosis. Although there is no 'magic bullet' to wipe out NMO-pain, Dr. Bhattacharyya talks through the number of ways to manage chronic pain including lifestyle changes, medications, devices and complementary treatments. Dr. Bhattacharyya also answers questions on opiates (not to be used as backbone of pain management and used sparingly!), medical cannabis, cryotherapy and mindfulness. Lots to learn!

In episode four of Open Up, Jess speaks with Dr. Matt Menard (Co-Director, Endovascular Surgery/Program Director, Vascular and Endovascular Surgical Fellowship/Assistant Professor, Harvard Medical School Vascular and Endovascular Surgery) about his winding path toward surgical medicine and the long term process of creating a cross departmental cardiovascular trial from idea to dissemination.  Dr. Menard discusses what makes the patient and surgeon relationship unique and the importance of removing departmental silos in an effort to generate productive research. He also expresses the need for community investment in research to ensure longevity and statistical significance for long term projects.  Quote of the Episode:  “I think science is our best honest effort to get to the truth” -Dr. Matt Menard

Dr. Atul Gawande, surgeon at Brigham and Women's Hospital, talks to Christiane Amanpour about the key steps to safely re-opening the United States and around the world. He delves into the lessons that can be learnt from hospitals as well as how we address mortality during the pandemic. Then – actress Julie Andrews is perhaps the most well-known nanny in the world; her iconic roles in “Mary Poppins” and “The Sound of Music” are cultural cornerstones. Her daughter Emma Walton Hamilton is an arts educator and children's author who she has collaborated with on several books. They speak about working on their new podcast series ‘Julie’s Library’ and why it’s important to release your imagination during lockdown. Finally, our Hari Sreenivasan talks to Guillaume Long, the former Ecuador Minister of Foreign Affairs, about the danger Covid-19 poses to democracy in Latin America. They reflect on the shocking pictures of carboard coffins and bodies left on the side of the streets in the small South American country.

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its 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 Greg Hundley, associate editor and Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr Carolyn Lam: We've got a juicy, juicy feature discussion coming up. It's on a pre-specified analysis of the ODYSSEY OUTCOMES randomized clinical trial, this time to ascertain whether PCSK9 inhibition reduces the risk of peripheral arterial disease events or venous thromboembolism after acute coronary syndrome. And, also to answer, these effects are related to levels of lipoprotein(a) or LDL cholesterol. I'm going to keep everyone guessing, as we get on our coffee chat and talk about the other papers in this issue. And I want to go first, because the first original paper I want to discuss is really quite related to the feature discussion too. And it asks the question, what is the relationship between cholesterol levels and risk of venous thromboembolism? And, what is the effect of PCSK9 inhibition on the risk of venous thromboembolism? So this is from Dr Marston from the TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School in Boston, Massachusetts, and colleagues who performed a post hoc analysis of the FOURIER trial, testing whether evolocumab reduces the risk of venous thromboembolic events. That is, deep venous thrombosis, a pulmonary embolism. The authors then looked at data from FOURIER and the ODYSSEY OUTCOMES trial and combined them in a meta-analysis to assess whether there was a class effect of PCSK9 inhibition on the risk of venous thromboembolism. As a reminder, the ODYSSEY OUTCOMES trial tested alirocumab as the PCSK9 inhibitor. Dr Greg Hundley: Well, Carolyn, what did they find? Dr Carolyn Lam: Well, first Greg, remember, this is the first study to demonstrate a significant reduction in venous thromboembolism with PCSK9 inhibition. Interestingly, the reduction in venous thromboembolism was associated with the degree of lipoprotein(a) lowering and not LDL cholesterol lowering, suggesting that lipoprotein(a) may be the mediator of venous thromboembolic risk. More coming up in our feature discussion. Dr Greg Hundley: Wow, Carolyn. Well, I'm going to go into the world of PCSKs, but talk about PCSK6. So this study involves a secretome analysis of cardiomyocytes as novel players in cardiac remodeling after myocardial infarction and the corresponding author is Dr Florian Leuschner from Heidelberg University. So Carolyn, we know that acute occlusion of coronary artery results in swift tissue necrosis and bordering areas of the infarcted myocardium may also experience impaired blood supply and reduced oxygen delivery leading to altered metabolic and mechanical processes. While transcriptional changes in hypoxic cardiomyocytes are well-studied, little is known about the proteins that are actively secreted from these bordering cells. So in this study, the authors established a novel secretome analysis of cardiomyocytes by combining stable isotope labeling and click chemistry with subsequent mass spectrometry analysis. Dr Carolyn Lam: Wow, sounds like very advanced methods and what did they find? Dr Greg Hundley: Okay. Carolyn lots of results here. They found that PCSK6 expression was elevated in hearts of mice, following three days of ligation of the left anterior descending artery, a finding confirmed by immunohistochemistry. ELISA measurements and human serum also indicated distinct kinetics for PCSK6 in patients suffering from acute myocardial infarction with a peak on day three post infarction. One of these beautiful studies combining basic science and human subjects in the same paper. In addition, adeno-associated virus nine mediated cardiomyocyte specific overexpression of PCSK6 in mice resulted in increased collagen expression and cardiac fibrosis as well as decreased left ventricular function after MI. So Carolyn, this study demonstrates how novel mass spectrometry-based approach allows the investigation of the secretome of primary cardiomyocytes. That's a first for that technique. And then analysis of hypoxia-induced secretion led to the identification of PCSK6 to be crucially involved in cardiac remodeling after MI, demonstrating increased collagen expression and cardiac fibrosis in those border zones. Dr Carolyn Lam: Wow, fascinating, Greg. Well, I want to switch tracks here. Maybe ask, when you're choosing between antithrombotic therapies for patients with atrial fibrillation and a recent acute coronary syndrome, have you ever wondered what is the tradeoff of risk? Risk of bleeding and benefit that would be in terms of prevention of ischemic events over time? Well, guess what, I'm not going to put you on the spot here because our next paper addresses this very question. And it's from corresponding author, Dr Alexander from Duke Clinical Research Institute and colleagues who performed a post hoc analysis of the AUGUSTUS trial. Dr Greg Hundley: Okay, Carolyn. I'm going to digress for just a minute here. We have this wonderful producer, Augie Rivera, and he's just fantastic and we should give him accolades because he really helps put all these together. Now I'm not going to ask him this time, but maybe in one of our future discussions, we may need to bring him into one of these because of his expanded knowledge of all of science, but getting back, Carolyn, can you remind us what is the AUGUSTUS trial? Dr Carolyn Lam: All right, so in the AUGUSTUS trial, patients with AF and a recent ACS and/or PCI taking a P2Y12 inhibitor had less bleeding and rehospitalization with apixaban, than vitamin K antagonists and less bleeding with placebo than aspirin. The composite of death or hospitalization was also reduced with placebo compared to aspirin. However, the risk of several recurrent ischemic events, including stent thrombosis, where numerically higher in patients assigned placebo. Further analysis of the stent thrombosis outcomes suggested that most of the increase in risk was early within 30 days of randomization. And hence the objective of the current paper, which is a post hoc analysis to explore the balance of risk and benefit using a variety of composite outcomes between randomization and 30 days and between 30 days and six months over time comparing apixaban versus vitamin K antagonists and aspirin versus placebo. So, here's what they found. Apixaban caused fewer ischemic and bleeding events than warfarin in the first 30 days after ACS and/or PCI and similar or fewer ischemic and bleeding events from day 30 to six months. Use of aspirin acutely, and for up to 30 days, resulted in an equal tradeoff between an increase in severe bleeding and reduction in severe ischemic events. However, after 30 days aspirin continued to increase bleeding without significantly reducing the ischemic events. So these results really informed shared patient-centric decision making regarding the ideal duration of use of aspirin after an ACS and/or PCI in patients with AF already receiving oral anticoagulation. Dr Greg Hundley: Very nice, Carolyn. You know, lots of data coming out about how we perform anticoagulation, the administration of aspirin, both an atrial fibrillation, ischemic events, those with stents and this is just another piece of important data that we're so fortunate to have published in circulation. Well in the rest of the issue Carolyn, there's a lot of information. I want to talk about a research letter from Dr Armand Killick from the University of Pittsburgh, and he describes the outcomes of the first 1300 adult heart transplants in the United States following a policy change in the U S related to allocation of hearts. In an EKG challenge, Dr Nobuhiro Takasugi from Gifu University and colleagues reviewed the etiology of wide complexes. Are they aberrantly conducted supraventricular beats? Are they premature ventricular complexes or intermittent ventricular prereq citation in an individual 70 years old presenting with symptoms of palpitations? Then Carolyn, in one of our COVID-19 articles, there's an in-depth piece by Dr Kevin Clerkin and associates from Columbia University. And they review coronavirus disease that is caused by severe acute respiratory syndrome, coronavirus 2 or SARS-CoV-2, which invades cells through the angiotensin converting enzyme or ACE-2 receptor. Among those with COVID-19, they note there is a higher prevalence of cardiovascular disease and more than 7% of patients suffer myocardial injury as evidence from elevated cardiac troponin values from the infection and in 22% of those that were critically ill. And despite ACE-2 serving as a portal for infection, the role of ACE inhibitors or angiotensin receptor blockers requires further investigation. And right now, as you know, in your field is a heart failure expert, they are not recommendations to consider discontinuation for those drugs. And then lastly, in a prospective piece, Professor Gianluigi Condorelli from Humanitas University in Milan, presents critical organizational issues for cardiologists in this COVID-19 outbreak, including prioritization of unstable patients with cardiovascular disorders by postponing visits, and in this situation they did so by 80%, reorganizing clinical activities in terms of ward, ICU beds and outpatient visits, using a hub-and-spoke model to prioritize management acute MI, and then finally rapidly acquiring and training physicians and staff in the correct use of PPE. All very valuable lessons from Italy that was so hard hit by this devastating disease. Dr Carolyn Lam: Indeed, and you know what, Greg, I just want to tell everybody about our circulation YouTube channel, where we have frontline interviews with people dealing with this from all over the world. Thank you to Augie and his team for making all of this happen. Let's go on to our future discussion, shall we? Dr Greg Hundley: Absolutely. Dr Carolyn Lam: Patients with acute coronary syndrome are at risk of peripheral artery disease events and venous thromboembolic events. Now we've heard a lot about PCSK9 inhibitors in patients with acute coronary syndrome, but what is the effect of PCSK9 inhibition on the risk of PAD or venous thromboembolic events? Well, we're about to find out. The feature paper is a pre specified analysis of the ODYSSEY OUTCOMES trial. And I'm so pleased to have the first and corresponding author, Dr Greg Schwartz with us from the University of Colorado, School of Medicine, as well as our guest editor, Dr Erin Michos from Johns Hopkins School of Medicine. So welcome. And Greg, could I ask you to start us off. Tell us why you looked at this in ODYSSEY OUTCOMES and what you found. Dr Gregory Schwartz: All of our patients or nearly all of our patients with acute coronary syndrome have had an atherothrombotic event and most of them also have a heightened inflammatory state. These factors are also thought to have a role in the pathogenesis of peripheral artery disease events, and perhaps also venous thromboembolism. We typically think of the risk factors for peripheral artery disease as being diabetes and smoking, and less so dyslipidemia, although dyslipidemia may play a role in PAD events as well. And although the association of LDL cholesterol levels with PAD events has been inconsistent in the literature, there's more consistency actually with levels of lipoprotein(a) and the risk of PAD events. And that kind of makes sense because we think that Lp(a) has both atherogenic and pro-inflammatory and perhaps also prothrombotic properties. So elevated levels of that lipoprotein might promote the risk of PAD events. Now statins, which are obviously the mainstay of our treatment of patients with atherosclerosis, lower levels of LDL cholesterol, but they don't affect the levels of Lp(a). In contrast, inhibitors of PCSK9 lower the levels of both of those key lipoproteins. So we looked at the relationship of baseline and on treatment levels of both LDL cholesterol and lipoprotein(a) on the risk of PAD events and also venous thromboembolism, which has been associated with lipoprotein(a) in some observational studies. Dr Carolyn Lam: Nice. So, could you tell us what were the results? Dr Gregory Schwartz: So first, we used data from the ODYSSEY OUTCOMES trial, which compared the PCSK9 inhibitor alirocumab with placebo in nearly 19,000 patients with a recent acute coronary syndrome. And as you mentioned, Carolyn, those patients may be at elevated risk for other types of arterial and venous atherothrombotic or thrombotic events. We had three goals in our analysis. First, we looked at the relationship of PAD and venous thromboembolic events to the baseline levels of lipoprotein(a) and LDL in the trial cohort. Second, we looked at the effects of randomized treatment on both of those types of events, PAD events, and venous thromboembolism. And lastly, we determined the relationship of treatment effects on lipoproteins to the risk of those events in the alirocumab active treatment group. What we found are four principle findings. First, although this was an acute coronary syndrome cohort, and there were only four percent of the trial cohort who had a prior history of PAD, there was nonetheless a substantial risk of PAD events. About two percent of the placebo group suffered a PAD event during the trial and about one percent had a venous thromboembolic event. In the placebo group. We found that there was a very strong association between baseline lipoprotein(a) concentration and the risk of PAD events. So to put that in a quantitative framework, if we compared the highest quartile of baseline lipoprotein(a) with patients in the lowest quartile of baseline lipoprotein(a), there was a more than twofold elevated risk of PAD events. And by that, I mean, critical limb ischemia, revascularization, or amputation for ischemia, more than a twofold elevated risk in the highest quartile of baseline lipoprotein(a). There was a non-significant relationship of venous thromboembolic events to the baseline concentration of lipoprotein(a). The patients who were treated with alirocumab, the PCSK9 inhibitor, achieved the expected approximately 50 percent reduction in LDL cholesterol and a median 23 percent reduction in lipoprotein(a) concentration. And those effects were associated with significant reduction in PAD events, a hazard ratio of point six nine, and a nearly significant peak, well point zero six reduction in the risk of venous thromboembolic events with a hazard ratio of point six seven. And incidentally, in the same issue of circulation, there is a companion paper from the FOURIER study, which looked at the risk of venous thromboembolic events with another PCSK9 inhibitor, evolocumab. They found something very, very similar. And again, the results of that trial individually were kind of on the margins of statistical significance, but putting the two trials together in their analysis, there was a highly significant reduction in the risk of venous thromboembolic events with PCSK9 inhibition, compared with placebo. They also related those effects to lipoprotein(a), but not to LDL cholesterol levels. So we found that the magnitude of the reduction in lipoprotein(a) was related to the reduced risk of PAD and VTE events, but a similar relationship between the magnitude of LDL cholesterol reduction and the risk of those events was not found. So to put it all together, lipoprotein(a) may be the stone that we haven't turned over, but should, when we encounter patients with PAD events or VTE events that we can't otherwise explain. And although these two trials were not purposed primarily to look at PAD events, the findings certainly suggest that treating elevated levels of lipoprotein(a) might be an effective strategy to reduce risk of PAD events and VTE. Dr Carolyn Lam: Wow. Congratulations, Greg, that was beautifully summarized. A novel on at least two levels, right? One is the PCSK9 inhibition effects on these two outcomes that we never thought of before. And second, that role of lipoprotein(a). Erin, could I bring you into this discussion? You were guest editor when this paper came across your desk. Could you tell us what were the considerations and frame how novel these findings are for us? Dr Erin Michos: Oh, Carolyn excited to be the associate editor for this paper. People who know me know; I love all things lipids. So as a preventive cardiologist, I'm very excited to have drugs like PCSK9 inhibitors in my toolbox. They are certainly known for their powerful LDL lowering effects, but also further lipoprotein little a reducing effect who these combined data show the PCSK9 inhibitors, not only reduced incident major adverse cardiovascular events and PAD events, but potentially can reduce VTE events as well in patients prescribed this therapy. So I thought it was really interesting and this new analysis from ODYSSEY, that it was the levels of lipoprotein little a, but not LDL cholesterol that predicted the risk of future PAD event and we saw a similar trend with VTE. And then furthermore, on treatment with alirocumab. It was the magnitude of Lp(a) little a reduction, but not LDL reduction that was associated with reduced PAD and VTE events. And so this suggests that the reduction of PAD events is mediated by the lipoprotein little a lowering and not the LDL lowering. You know, lipoprotein(a) is a particularly risky type of LDL. It's strongly inheritable it's atherogenic similar to LDL, but prothrombotic, so it's this double whammy of badness due to its structural homology with plasminogen competes with berberine binding and inhibits tissue plasminogen activator and ultimately inhibits fibrinolysis. And so that's why lipoprotein(a) may be a mediator of this apparent effect of PCSK9 inhibitors with PAD and VTE incidents. So how do I put this in practice? Prior to PCSK9 inhibitors, we really didn't have any lipid modifying therapies to actually lower lipoprotein little a, except niacin, which we don't really use. This was mentioned by Greg, statins don't really lower lipoprotein(a) and they actually increase lipoprotein little as levels. Although we do know that statins of course reduce ASCBD risk. So, I'm checking lipoprotein little a now in all my secondary prevention patients with established CVD and in high risk primary prevention with those with family history. While we're all anxiously awaiting outcome trials, such as the antisense oligonucleotides that can lower lipoprotein(a) by 80 percent, that therapy is not here now, we don't have that available in practice. But we do have PCSK9 inhibitors now, which can reduce lipoprotein little a by 20 to 25 percent and have meaningful outcome data like the alirocumab data we see here in this ODYSSEY OUTCOMES study. With a 31 percent reduction of PAD, that is really meaningful. So I'm particularly excited about PCSK9 inhibitors and my patients with PAD who often have concomitant CAD, polyvascular disease, and then regarding the VTE effects, I think we should point out that the absolute risk reduction of VTE was pretty modest. We didn't really see significance until we combined it with the FOURIER data. So I think given the cost of the drug, it's not warranted to prescribe PCSK9 inhibitors to the general population, specifically for VTE prevention alone. But in patients with ASCBD, who would be recommended for a PCSK9 inhibitor to reduce incident CBD, you know, there may be this added special benefit of reducing risk of VTE as well. Dr Gregory Schwartz: I just wanted to comment on a few things that Erin said, I think we’re really important. All of these patients were on intensive statin therapy in the background. So although we did not see a relationship between the further reduction in LDL cholesterol with alirocumab and the risk of these events, it doesn't mean that lowering LDL cholesterol has nothing to do with the risk of those events because everybody was on background statin therapy, 90 plus percent. So, I think that's important to point out. And I think the comment that was made about when to check a lipoprotein(a) level is very pertinent. And, in the European guidelines, they direct us to check lipoprotein(a) at least once in a lifetime for everyone, even if there's no other signs or risk factors for cardiovascular disease. So I think as Erin indicated, with some tools in the toolbox now, and more tools, perhaps on the way with both the antisense, and also there are small interfering RNA approaches to lower lipoprotein(a), we should get more accustomed to looking at this, to turning over that stone. Even if we're not a hundred percent certain what to do with what we find underneath it, we should still look because there may be some things we can do in the interim. Dr Carolyn Lam: Thanks, Greg. Erin, can I give you the last word? Any take home messages? Dr Erin Michos: I definitely think that as we move forward with other therapies such as the small interfering RNA and the antisense oligonucleotides, we need really more phase three clinical trials specifically assessing VTE. And then I just want to mention, although I didn't write an editorial for this study, I did have the pleasure of writing an editorial for another ODYSSEY OUTCOMES analysis that was published in December. You know, my editorial was entitled, "Achievement, a Very Low LDL. Is it Time to Unlearn the Concern for Hemorrhagic Stroke?" And I mention this because one of the barriers I get in clinical practices, people get very worried about the very low LDL levels that we see with PCSK9 inhibitors and I think important to point out from ODYSSEY that, with the reduction in ischemic stroke, that there was no signal for increased hemorrhagic stroke and that provides additional reassurance. So I think that's important to mention, I think this PCSK9 therapy is being under-utilized in clinical practice and ASCBD and PAD, these are really high-risk patients who have really high risk of recurrent events and our efforts to ward off these devastating consequences. We need to make sure that we're appropriately utilizing this important therapy. Dr Carolyn Lam: Thank you so much, Erin. Thank you so much, Greg. You've been listening to Circulation on the Run. Don't forget to tune in again next week. Dr Greg Hundley: This program is copyright, The American Heart Association, 2020.  

The month of May is Mental Health Awareness. In this episode, Dr. Samantha Meints, who is a licensed clinical psychologist, will share her career path as a clinical psychologist and tell us how the body and mind react to the physiological and psychological pain and stress and how does stress impact our immune system. She will share timeless tips on pain and stress management to improve our mental health. Dr. Meints is a licensed clinical psychologist in the Pain Management Center at Brigham & Women’s Hospital at Harvard Medical School. She attended Indiana University-Purdue University Indianapolis, completing a Ph.D. in Clinical Psychology with a focus in Behavioral Medicine. She then completed a postdoctoral fellowship at Brigham and Women's Hospital, before joining the faculty there. Dr. Meints’ research focuses on biobehavioral aspects of acute and chronic pain. Questions discussed in the episode: 1. What is a clinical psychologist? 2. How much stress can the human heart endure? 3. What is the difference between physical stress and emotional stress on our health? 4. How does stress impact our immunity? 5. How do we reduce stress? 6. Any advice on how to be healthy while working at home? 7. Any final golden nugget of advice for our listeners on handling stress under these extreme special circumstances: 1) If you realize you just test positive for the COVID19, how do you handle your stress? or 2) If you realized that your loved one has tested positive, and you didn’t (is there a survivor guilt), how do you both handle your stress? or 3) If you realized that you infected someone unintentionally (a sense of guilt), how do you handle your stress? Connect with Dr. Samantha Meints by email, twitter or Linkedin --- Send in a voice message: https://anchor.fm/whatispublichealth/message Support this podcast: https://anchor.fm/whatispublichealth/support

Dr. David Steensma discusses MDS and toxins with Leigh Clark, Patient Educator. Dr. Steensma is an associate professor at Harvard Medical School and faculty member in the leukemia program at the Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston, Massachusetts and the Edward P. Evans Chair in MDS at Dana-Farber Cancer Institute

Dr. Daniel Kuritzkes, with Brigham and Women's Hospital, said that people "really don't need to be concerned about carbon dioxide build-up" in their mask while exercising. WBZ NewsRadio's James Rojas reports.

Felger, Massarotti, and Jim Murray kicked off the show sharing their opening thoughts before taking calls on an Agenda Free Friday.  Mike and Tony were joined by Dr. Paul Sax, of Brigham and Women's Hospital, to discuss the latest in the Covid-19 pandemic.

People who have diabetes, a heart condition, cancer, kidney disease or other underlying condition are impacted more severely if they contract the coronavirus. Harvard Medical School endocrinologist Dr. Enrique Caballero explains why. Dr. Caballero is on the staff of Brigham and Women's Hospital in Boston, Massachusetts, and is the director of diabetes education in the post-graduate medical education department at Harvard Medical School.

Dr. Sharon Bergquist is a Rollins Senior Distinguished Clinician, Master Clinician, and Assistant Professor of Medicine in the Division of General Medicine and Geriatrics at Emory University School of Medicine. She earned her Bachelor of Science from Yale University and medical degree from Harvard Medical School. She completed her internship and residency at Harvard's Brigham and Women's Hospital. She is a Fellow of the American College of Physicians and member of the American College of Lifestyle Medicine.Dr. Bergquist strongly believes in personalized and comprehensive health management and incorporates prevention and wellness strategies into her practice. Her expertise includes diabetes and heart disease prevention and management, nutrition and obesity counseling, women's health, and the management of mood disorders such as anxiety and depression.Dr. Bergquist is the Medical Director of Emory's Executive Health program and leads the research program at the Paul W. Seavey Comprehensive Internal Medicine Clinic. She also founded and directs Emory Lifestyle Medicine & Wellness. She has been on the Emory faculty since 2000 and sees patients at the Paul W. Seavey Comprehensive Internal Medicine and Emory Executive Health practices.Dr. Bergquist is also a host of The Whole Health Cure podcast.In this conversation Dr. Bergquist shares her personal story and what inspired her to use lifestyle change, including plant-based nutrition as a tool to heal her patients. We talk about the effects of stress and how to shift your perspective and use it for getting stronger. We discuss plant-based nutrition and why not all doctors recognize its potential. Finally, we discuss some of the projects that we are working on at Emory and Dr. Bergquist shares her vision for programs that she thinks could make a true impact.Tune in to learn more!Resources:The Whole Health Cure podcastEmory Lifestyle Medicine & WellnessTed Talk - How Stress Affects Your BodyWebsite

Quincy Nurse Debbie Buonopane talks about her experience going from a nurse treating Covid-19 patients at Brigham and Women's Hospital to being a patient with the virus.

In this reprise from last fall, Kathy McManus, director of nutrition at Brigham and Women's Hospital, discusses changing behavior as a pathway to weight loss in this conversation with Harvard's Dr. Mallika Marshall. Their views appear in the Harvard online course 6-Week Plan for Healthy Eating.

There are certain clinical nuances in medical and/or scientific communication that gets lost in translation when communications professionals without background on the subject are left to relay these messages on their own. This is why Dr. Austin Lee Chiang Medical made it one of his biggest goals to get more clinicians on social media to talk about their work and to help educate the public. But this requires the ability to distill science for public consumption without dumbing down the information. This line between jargon and layman’s term is what science professionals need to tread in order to get their message across the right way. Dr. Austin Lee Chiang is an Assistant Professor of Medicine at Sidney Kimmel Medical College, Director of the Endoscopic Bariatric Program, and the Chief Medical Social Media Officer at Jefferson Health. He's also the Founding President of the Association for Healthcare Social Media, an advisory board member of the Association for Bariatric Endoscopy, and he is also on committees for the leading national GI societies.  Dr. Chiang is triple board certified in Gastroenterology, Internal Medicine, and Obesity Medicine. He completed an Advanced Endoscopy Fellowship at Thomas Jefferson University Hospital before staying on as faculty. Prior to that, he obtained a Master's in Public Health from Harvard University's T.H. Chan School of Public Health. At about the same time, he trained in Gastroenterology and Hepatology at Brigham and Women's Hospital where he completed the fellowship in Geriatric Endoscopy.  Dr. Chiang received his MD and completed his Internal Medicine residency at Columbia University. Before that, he attended Duke University where he obtained his bachelor’s degree in Biology.  What You’ll Hear On This Episode of When Science Speaks Dr. Austin Lee Chiang talks about why he’s on TikTok and what he hopes to achieve by joining the platform How Dr. Chiang distills medical information into the limited time in TikTok videos  How Dr. Chiang comes up with topics for his posts on social media  Things Dr. Chiang hopes to achieve as Chief Medical Social Media Officer at Thomas Jefferson University Hospital How Dr. Chiang’s colleagues relate with him as the Chief Medical Social Media Officer  Should scientific information be shared on Instagram?  Dr. Chiang gives tips on how clinicians and health organizations can get started with using social media and how to choose which platform to use Connect with Austin Lee Chiang, MD Sidney Kimmel Medical College LinkedIn for Austin Lee Chiang, MD Dr. Austin Lee Chiang on Instagram Dr. Austin Lee Chiang on Twitter Dr. Austin Lee Chiang on Tiktok Health Information Sharing  How much of the health information patients receive during when speaking with a medical practitioner actually sticks with them? Dr. Austin Lee Chiang says that not a lot of information is retained by patients because of the huge mental load it gives, and this opens up patients to the risk of misinformation which can easily be spread through social media. Like wildfire, misinformation can spread so fast and this can lead to bigger problems for the public and for the medical society. This is why Dr. Chiang believes that it’s important for health professionals to make themselves visible on social media in order to share information in a manner that can be easily understood yet is still accurate. He himself has been using various social media platforms to reach out to people not only to share his experience as a doctor with those eager to join the medical field but also to share his knowledge with people in a bid to fight the proliferation of misinformation. Distilling Science for Public Consumption  Granted, there’s no hard and fast rule for sharing scientific or medical information in a way the public can understand. For Dr. Chiang, he says that putting yourself in the shoes of patients and the public helps him choose topics to cover in the limited time frame allotted in social media. By trying to see things from the perspective of the audience, he is able to figure out what to share and how to best convey the relevant information in the most comprehensible way possible. However, Dr. Chiang says that although social media is most a lot of humor and fun, health professionals should make sure that they are being thoughtful with how they portray patient interactions and the work that they do to avoid misconceptions and misunderstandings. Optimizing social media advantages is a great tool for health professionals but they should still keep in mind that they are professionals and that what they do is in the service of the public. Choosing the Topics to Cover on Social Media  Dr. Chiang bases the topics he covers on his social media accounts on his expertise, his experience, and some of the common questions he encounters when dealing with patients. He says that sharing useful and helpful information that the public can easily understand is a responsibility that healthcare professionals should take seriously. Accurate representation of data, information, and healthcare tips is more important than just being fun and relatable. By choosing to go for topics that you have a wealth of knowledge on, you can guarantee that what you share will be what is truly needed by your target audience. Learn more about Dr. Austin Lee Chiang on this week’s episode of When Science Speaks. Connect With Mark and When Science Speaks http://WhenScienceSpeaks.com https://bayerstrategic.com/ On Twitter: https://twitter.com/BayerStrategic On Facebook: https://www.facebook.com/Bayer-Strategic-Consulting-206102993131329 On YouTube: http://bit.ly/BSConTV On LinkedIn: https://www.linkedin.com/in/markdanielbayer/ On Instagram: https://www.instagram.com/bayerstrategic/ On Medium: https://medium.com/@markbayer17  

THIS EPISODE WAS MADE IN COLLABORATION WITH THE PEDIATRIC OVERFLOW PLANNING CONTINGENCY RESPONSE (POPCoRN) NETWORK https://www.popcornetwork.org/   Course: Crash Course in Adult Inpatient Medicine - Pulmonary Course Director: Tony R Tarchichi M.D.  - Associate Professor in Dept of Pediatrics at the University of Pittsburgh Course Director: John Kennedy M.D. - Associate Professor in Pulmonary & Critical Care Medicine at Brigham and Women's Hospital.  Course Director: Ahmet Z. Uluer D.O. - Associate Professor in Pulmonary & Critical Care Medicine at Brigham and Women's Hospital.  Disclosures: None This Podcast series was created for Pediatric Hospitalists or those healthcare professionals who take care of hospitalized children.  This episode is Crash Course in Adult Inpatient Medicine - Pulmonary. As always there is free CME credit of up to 1 AMA category 1 for listening to this podcast and going to the Univ of Pitt site. See the link below.  ______________________________________________________ Objectives: Upon completion of this activity, participants will be able to: Review Differences between Asthma in adults and Pediatrics. Review invasive and non-invasive airway procedures for adults with respiratory distress due to COVID-19. Review COPD in adults and acute exacerbation treatments. ______________________________________________________ Released:  4/13/2020, Reviewed 4/13/2020, Expire: 4/13/2021 If you are new to the Internet-based Studies in Education and Research (ISER) website (which is how you will get your CME credit), you will first need to create an account: Step 1. Create an Account https://www.hsconnect.pitt.edu/HSC/home/create-account.do If you have used the ISER website in the past, you can click on the link below and then log onto in order to complete the evaluation for this training: Step 2. To access the test for CME credit:   Accreditation Statement: The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The University of Pittsburgh School of Medicine designates this enduring material for a maximum of  (1)  AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Tired of reading contradictory facts about Covid-19? Same! Thankfully, Harvard Medical School's own, Dr. Abraar Karan, is here to breakdown the scientific facts about the virus. If you are curious about how coronavirus spreads, how long it lasts on surfaces or in the air, why some people asymptomatic, the current treatments being used, and why we are just now being recommended to wear masks- this is a MUST listen. Dr. Abraar Karaan is an internal medicine doctor at the Brigham and Women's Hospital and Harvard Medical Schoo along with his involvement with the Doris and Howard Hiatt Residency in Global Health Equity. He earned his MD from the UCLA David Geffen School of Medicine, an MPH from the Harvard T.H. Chan School of Public Health; a Diploma in Tropical Medicine and Hygiene (DTM&H) from the London School of Hygiene and Tropical Medicine; and his undergraduate degree w/ distinction from Yale. Over the past two years, Dr. Karan has been studying epidemic response as a more specific example of these themes. His previous work over the past 13 years has included projects working on combatting infectious diseases in Latin America (Mexico, Honduras, Nicaragua, Haiti, Dominican Republic), Asia (India, Thailand), and Sub-Saharan Africa (Rwanda, Uganda, Mozambique). His writings and medical journals have been featured in the New England Journal of Medicine, The Lancet, The BMJ, Academic Medicine, Health Affairs, NPR, Vox, Los Angeles Times, Scientific American, Huffpost, the Boston Globe, and other major publications. His book, "Protecting the Health of the Poor", was released in December 2015 and is available on Amazon. Causebox - Visit causebox.com/life for 30% your first Causebox with code LIFE. Produced by Dear Media

Dr. Atul Gawande, surgeon at Brigham and Women's Hospital and staff writer at the New Yorker, joins Christiane Amanpour to outline the importance of protective equipment for our frontline health care workers and how we at home can employ simple strategies to prevent the spread of the coronavirus. Nick Clegg, VP for global affairs and communications at Facebook and former British Deputy PM, answers questions about what Facebook are doing to stop the spread of misinformation about Covid-19 and how the social media giant have learnt from their past mistakes. Our Walter Isaacson talks to Jon Meacham, the presidential historian and biographer, about what we can learn about previous presidents and their handling of various crisis situations. He assesses how leaders around the world are handling this pandemic. David Beasley, executive director of the World Food Programme and former Governor, talks candidly about recovering from corona virus and how he nearly confused his symptoms with allergies. He talks about how the WFP's work can continue during this outbreak.

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: I'm Greg Hundley, associate editor from the VCU Pauley Heart Center in Richmond, Virginia. Dr Carolyn Lam: Greg today's speaker paper is all about soy products and whether or not there is a benefit with them with regards to risk of coronary heart disease. Now, this has been extremely controversial and today's speech or paper is really important in its findings. Ha ha, I bet you want to get to it right now but I'm going to say, hold on let's get to some other really interesting papers in this series first. Can I start off? You got your coffee? Dr Greg Hundley: Yes. Let's get going Carolyn. Dr Carolyn Lam: So the first paper I want to highlight really talks about myocardial energetics in obesity, and you're going to love this one Greg it's got some really cool MRI techniques. We know that obesity is strongly associated with exercise intolerance and the development of heart failure particularly HFpEF. Well Dr Rayner from University of Oxford and colleagues looked at this carefully in 80 volunteers, which included 35 controls with an average BMI of 24 and 45 obese individuals with an average BMI of 35, who did not have coexisting cardiovascular disease. Now, these participants underwent body composition analysis and MRI of the abdominal liver and myocardial fat content, left ventricular function and 31 Phosphorus Magnetic Resonance Spectroscopy to assess Phosphocreatine ATP and Creatine Kinase Kinetics at rest and during Dobutamine Stress. Dr Greg Hundley: Oh, wow Carolyn, this is right up my alley. You've got MRI imaging for body composition coupled with MR spectroscopy for metabolism, so what did they find? Dr Carolyn Lam: Thanks for putting that simply for us Greg. They found that in the obese resting heart, the myocardial creatine kinase reaction rate is increase, maintaining ATP delivery despite reduced energy stores during increased workload. While the non obese heart increases ATP delivery through creatine kinase the obese heart does not, and this is associated with reduced systolic augmentation and exercise tolerance. Weight Loss reversed these energetic changes, so these findings really highlight myocardial energy delivery via creatine kinase as a potential therapeutic strategy to improve symptoms in obesity related heart disease, as well as a fascinating modifiable pathway involved in the progression to heart failure. Now with this paper the central illustration is so critical, everybody has to pick up that issue and have a look. Furthermore, you must read the elegant editorial by Barry Borlaug and Craig Malloy. Dr Greg Hundley: Oh, you bet Carolyn. Craig always puts these MR spectroscopy papers in such fantastic perspective, really looking forward to that read and such an elegant study. Now, we haven't had Carolyn's quiz in weeks and we're going to get into one. This paper comes from Professor Nina Wettschureck, from the Max-Planck-Institute for Heart and Lung research, and it pertains to the infamous G-protein coupled receptors. Now, Carolyn here's your quiz and guess what, it's just multiple choice. All you have to do is fill in the blank. Dr Carolyn Lam: On G-protein coupled receptors? Dr Greg Hundley: Yeah, I know it's... we know a lot about these, but we're going to learn. So, G-protein coupled receptors are the largest family of transmembrane receptors in eukaryotes. They transduce signals of numerous physio-chemical stimuli including... and Carolyn you have to complete this sentence. So it's neurotransmitters, hormones, local mediators, metabolic or olfactory cues and got to complete the sentence. Is it air resistance? Time? Or light? Dr Carolyn Lam: Space. Dr Greg Hundley: That's not a choice. Dr Carolyn Lam: All right, all right let me guess light. Dr Greg Hundley: That's awesome. Fantastic, great job Carolyn. So in the vascular system the contract alternative vessels is crucially regulated by these GPCRs, including basic constrictors such as Angiotensin two and Endothelin one. In this study the investigators studied the role of GPRC5B, and the regulation of contractility and differentiation in human and murine smooth muscle cells in vitro, as well as in tamoxifen inducible smooth muscle cells Pacific knockout mice under conditions of arterial hypertension and atherosclerosis, and these experiments were done in vivo. Dr Carolyn Lam: Okay, so what were the results? Dr Greg Hundley: They found that GPRC5B regulates vascular smooth muscle tone and differentiation by negatively regulating prostate cycling receptor signaling. Thus, Carolyn inhibition of the interaction between GPRC5B and the prostacyclin receptor might be beneficial in human arterial hypertension and vascular remodeling. What a great new insight into basic science. Well, let me get on I have a clinical paper, and this is on the infamous topic from the COMPASS-PCI trial, Rivaroxaban plus Aspirin versus Aspirin alone in patients with Prior Percutaneous Coronary Intervention from Dr Kevin Bainey at the Canadian VIGOUR Center in University of Alberta. So Carolyn, the cardiovascular outcomes for people using anticoagulation strategies or COMPASS trial demonstrated dual pathway intervention with Rivaroxaban 2.5 milligrams twice daily plus aspirin, and 100 milligrams once daily versus aspirin 100 milligrams once daily, reduced the primary major adverse cardiovascular event outcome of cardiovascular death, MI or stroke as well as mortality in patients with chronic coronary syndromes or peripheral arterial disease. Now, whether this remains true in patients with a history of PCI is unknown. Dr Carolyn Lam: Oh, Greg I'm so disappointed. Why didn't you give me a quiz here? I know about the COMPASS trial. Okay, so what did the author's find? Dr Greg Hundley: So Carolyn of the 27,000 plus patients in COMPASS 16,500 plus patients had chronic coronary syndrome, were randomized to DPI or aspirin and of these 9,862 had prior PCI. So here are the results, DPI compared with aspirin produce consistent reductions in MACE mortality, but with increased major bleeding with or without prior PCI. So among those with prior PCI one year and beyond, the effects on MACE and mortality were consistent irrespective of time since the last PCI. Dr Carolyn Lam: Mm-hmm (affirmative) Interesting implications on dual platelet inhibition. Well, let me tell you a little bit about what's in the mailbag in the rest of this issue. There's a research letter by Dr Joseph Wu on molecular signatures of beneficial class effects of statins on human induced pluripotent stem cell derived cardiomyocytes. We have global rounds by Dr Annika Rosengren and Dr Lars Wallentin on the cardiovascular medicine in Sweden. We have a White Paper by Dr Abhinav Saxena and colleagues on the value of hemodynamic monitoring in patients with cardiogenic shock undergoing mechanical circulatory support. And we also have paired perspective pieces, one by Dr Salim Virani and colleagues on secondary prevention of atherosclerotic cardiovascular disease comparing recent United States and European guidelines on dyslipidemia, and another by Dr Neil Stone and colleagues on comparing primary prevention recommendations with the focus look at the US versus European guidelines on dyslipidemia. Dr Greg Hundley: Very good, Carolyn. Well, I've got a research letter Professor Do-Young Kwon from the Korea University of Ansan Hospital, Korea University College of Medicine and discusses the association of Parkinson's disease with the risk of cardiovascular disease and all-cause mortality, and a nationwide population-based cohort study. In addition, different series of letters Dr Seung-Jung Park from Asan Medical Center at the University of Ulsan College of Medicine, and Professor Lang Li of The First Affiliated Hospital of Guangxi Medical University exchanged letters regarding the article, Clinically Significant Bleeding With Ticagrelor versus Clopidogrel in Korean patients with Acute Coronary Syndromes Intended for Invasive Management, that previously published randomized clinical trial. Then finally one of those great ECG investigations from Dr Miguel Arias, and they have an ECG quiz entitled The Hidden Reveals the Hidden, but really, it's referring to a Brugada ECG pattern and a patient with Wolff-Parkinson-White. I can't wait to get onto that feature article discussing the potential benefits or harms of soy in men and women as it relates to cardiovascular disease. Dr Carolyn Lam: Yeah, you and I Greg let's go. Oh, boy today's feature paper really literally cuts close to the heart for me talking about soy products, and whether or not there's a relationship with cardiovascular health. This remains controversial but thankfully we've got really great data just published in this week's issue, so proud to have the first author with us Dr Qi Sun from Brigham and Women's Hospital, as well as our associate editor who's also an editorialist for this paper and that's Dr Mercedes Carnethon from Northwestern University Feinberg School of Medicine. So welcome both I cannot wait to just jump right into it. Please, Qi, tell us what you found about soy products. Dr Qi Sun: First off this is a prospective cohort study that included three cohort studies, the Nurses’ Health Study and the Nurses’ Health Study II and Health Professionals Follow-Up Study. So those three big prospective cohort follow up studies. Now over the years we have collected much data of diet which has been repeated, reviewed, and assessed over the years, and we have accumulated many cases of cardinal heart disease the numbers are a solid. Now what we found is that the intake isoflavones which are the big family are flavonoids, the higher intake of isoflavones were associated with a lower risk of developing coronary heart disease in those three cohorts of men and women. And in addition because tofu and soy milk are the primary contributor in our guide of isoflavones, we also examine the tofu and soy milk in relation to the risk of cardinal heart disease What we found is that tofu intake is significantly associated with lower risk of developing heart disease, and soy milk is also associated with lower risk of developing heart disease. It's just the association for soy milk, soy milk is not significant. And I think very interestingly we also found that the menopausal status and the postmenopausal hormone use somewhat also modulated association primarily for coffee intake with heart disease risk, in that we found younger women who were before their menopause and also postmenopausal women who did not use hormone will benefit more from tofu intake. In contrast, for postmenopausal women who are using hormone the association was not significant. I think those are the primary findings of our prospective cohort study. Dr Carolyn Lam: Oh my goodness, hallelujah. That's really marvelous and beautifully summarized, Mercedes please explain why was this such a controversial area before? And what does this paper add? Love your editorial by the way. Mercedes Carnethon: We hear a lot about nutritional epidemiology studies, and we have a lot of debates about what we should believe, whether we should change our behavior based on these observational studies and quite often we have discussions about what's new. And I lean on that final point about why I like this particular paper so much, and that's because I found the topic of isoflavones, tofu intake and soy to be extremely relevant to a large proportion of the world's population, whose primary protein intake may be something made from a soybean, heavy and isoflavones. Within the United States it's also relevant even though a smaller proportion of our population relies primarily on vegetarian diet, there is a very large and interested group wondering whether soy intake is safe. There have been discussions about whether there's harm associated with it, and the possibility that it could have beneficial influence on our leading causes of death of coronary heart disease. So I was most thrilled about the innovation of this particular topic, and its methodological rigor. When we think about what we lean on, we lean on large studies, we lean on multiple events and the size of the study allowed the investigators to explore numerous subtleties. Subtleties such as that reported related to the moderation by menopausal status, and that was the point I was most curious about and why I'm really excited to have an opportunity to talk to you today Chi. Can you tell me a little more about the menopausal status finding? Dr Qi Sun: So first off as I mentioned tofu intake was more strongly associated with lower risk of developing heart disease among younger pre-menopausal women, or postmenopausal women who did not use ham. Before that I want to also mention for isoflavones intake where I also found a similar pattern in that isoflavones are more. Appear to be more strongly associated with lower risk also in those two groups of women, although the past by interaction was non-significant. Now in terms of why I think there are a couple reasons why is that, among postmenopausal female or in our use hormone, the isoflavone can function as estrogen and provide at least partially the estrogenic effects that were calculated in postmenopausal women who do not use hormone, and for premenopausal women we think that's probably because before menopausal, the activity of estrogen receptor may be higher than the estrogen receptor after menopausal. So, in reality, the other variables of isoflavones may provide estrogen effects after menopausal. So those are the hypotheses although I have to mention that those hypotheses, we need more evidence to really shed light on the mechanisms underlying those interactions between menopausal status, postmenopausal hormonal use, where's the intake of isoflavones and tofu. Dr Carolyn Lam: So Chi I love that explanation and giving it some biological possibility, although as you said it's a postulation. But may I ask so what's the implication for men? I lived with a man who thinks if he takes soy he's going to grow boobs. So what... did you see any sex differences and do studies like this and able looking for the downsides of eating soy? Dr Qi Sun: As a scientist I'm open to any kind of new findings as long as the findings are from well conducted, rigorously designed study. But having said that I couldn't exclude the possibility that maybe soy intake is associated with certain adverse health outcomes, but so far based on my experience I didn't see any such evidence. But having said this I always say I wouldn't risk any possibility, but coming... circling back to the coronary heart disease we really didn't see much difference between men and women. It's true for the younger women we saw a stronger association but for men I also see a lower risk of heart disease. So there's a kind of interesting image on soy intake or isoflavones intake in the United States that people believe they are estrogen so a man shouldn't take it, but if you look at the group of vegetarians, the vegans. There are a lot of guys they practice vegetarian, they practice vegan diets and we also publish on plant-based diet in relation to coronary heart disease and lot of men eat very healthy. And we found those people who practice those kinds of healthy diets, soy is often mouthful of primary sources of proteins and if you look at their risk of developing heart disease, type two diabetes is quite low. Something lower than other normal women who practice otherwise omnivore diet. Dr Carolyn Lam: It's true Qi soy intake could also be a marker of a healthier lifestyle in general, by extension of what you just said. But Mercedes I love that you discuss quite a number of these issues in your editorial and at the end of the day you asked the most important question, what does this mean for us? Should we all be increasing our intake of soy products? Could you give us your synthesis of that? Mercedes Carnethon: Yes, a point that I've definitely tried to make here, and this is really in response to what I expect to be the media fear surrounding new dietary findings. One of the first questions that I know that she and his colleagues will be asked is, should I change my diet? Can I extend my life? And that's because the media is really looking for a lot of sensational headlines in this topic, and I think we have to focus on what we learn from these observational studies. They're a very important step in the scientific process that helps us provide a justification for later clinical trials, that helps us think about the multiple components that work together to promote overall excellent health. And the point you were making right before this about the individuals who eat plant based diets that are heavily based in soy. In the paper it also describes that those individuals exercise more, they may have lower intakes of saturated fat, and so I think ultimately what I take from this at least for myself and for people who would ask is that an overall healthy diet seems to stand up very well in these well done observational studies. And that soy in particular may be a part of an overall healthy diet given what we're seeing here in this very well done study. Dr Carolyn Lam: Oh, that's beautifully put Mercedes and Chi perhaps I can give you the last word. What would you say is the take home message and what are next steps? Dr Qi Sun: I think the core message is this as Mercedes very well discussed, I think soy and especially tofu can be really good components of the overall healthy plant based diet, and by practicing that I think we can significantly reduce the risk of developing coronary heart disease for both men and the women. I think moving forward we would like to see evidence from clinical trials that target cardiometabolic risk factors as outcome, and to see whether increased consumption of tofu and isoflavones can really reduce those risk markers so that they have ample evidence to support the mechanisms. As you mentioned Carolyn that this is an initial study, and it could be soy, intake could be just macro how is it, through clinical trials, we can really control those confounding factors and really provide good evidence to support our findings. Dr Carolyn Lam: Well, in the meantime I just have to say you made my day this is coming from a soy eating vegetarian, so thank you so, so much. Thank you, listeners for joining us today. Dr Greg Hundley: This program is copyright the American Heart Association 2020.  

Dr. Kaneko, a cardiac surgeon at Brigham and Women's Hospital, breaks down a trio of studies he was associated with from ACC.20, including a look into PLO FLOW TAVR, the July Effect, and alternative access TAVR.

World expert urogynecologist Neeraj Kohli MD and  founder of Harvard's division of Urogynecology at Brigham and Women's Hospital sat down with Marco Pelosi III MD for a far reaching conversation on the most promising new technologies in pelvic medicine.  We covered so much ground and went into such a high level of clinical detail that I thought it best to divide the conversation into two podcasts. In the Part 1, we explore high intensty focused electromagnetic therapy (HIFEM), specifically the Emsella chair with a no-holds-barred debriefing. Dr. Kohli delivers magnificently and provides phenomenal tips and insights. The treatment of urinary incontinence is only the tip of the iceberg. Whether you are a physician or a patient, sit back, relax and enjoy. ​ _____________________ Dr. Kohli can most easily be reached at nkohli@bostonurogyn.com Dr Marco Pelosi III can be reached most easily at drmarcopelosi.com  

A look at the experiences of patients in an ICU, who, due to new hospital policies, are unable to see family.Guest: Daniela Lamas, a pulmonary and critical care doctor at the Brigham & Women's Hospital.Read the transcript: https://tradeoffs.org/2020/04/02/cc-lamas/See all of our coronavirus coverage: https://tradeoffs.org/coronavirus/Follow us on Twitter: https://twitter.com/tradeoffspod See acast.com/privacy for privacy and opt-out information.

With that in mind, we discuss some famous NDE experiences including Dr. Eben Alexander, former academic neurosurgeon Harvard School of Medicine and Brigham & Women's Hospital. We also cover our take on whether he went to heaven as he claims, or somewhere else, as we speculate. We cover two additional NDE and Lucid Dream experiences that point to evidence that the people who died (if that be the case) this month, of COVID-19, are not dead, but in a state of being in universal consciousness. Three case studies advanced conversationally by Dr. John LaCasse Ph.D. From the Ross Stewart Andrew Studio in Seattle --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/john-lacasse/message

Dr. Syed Moin Hassan was riled up. "I don't know who needs to hear this," he posted on Twitter, "BUT YOU ARE NOT LAZY IF YOU ARE WAKING UP AT NOON." Hassan, who is the Sleep Medicine Fellow at Brigham and Women's Hospital in Boston, speaks to Short Wave's Emily Kwong about de-stigmatizing sleeping in late, and why a good night's rest is so important for your immune system. Email the show at shortwave@npr.org.

Dr. Lisa Rosenbaum, a cardiologist at Brigham and Women's Hospital speaks to Emily Gutowski, a 4th year medical student at Harvard Medical School, about her unique career as a clinician and physician-writer for the New England Journal of Medicine (NEJM) as the National Correspondent. They also shed light on aspects of gender disparity in medicine, finding role models, and avoiding burnout in the ever-changing field of cardiology. https://www.runthelistpodcast.com/cardiology/#careers

Introducing "GOING VIRAL: Staying Sane, Healthy & Connected during the Coronavirus Outbreak of 2020." This daily podcast was born out of necessity as a way for us to stay connected during this unprecedented nationwide/global quarantine during the outbreak of COVID-19. **Please Note: The opinions expressed in this podcast are my own and my guest's own. If you are experiencing a true medical emergency or symptoms, please call 911.** (My apologies for the poor Skype recording! Working to fix this on the next call!) -->I'm pleased to introduce my first guest, Mary Hearn Kelley, RN, Cardiology Nurse at the world-renowned Brigham and Women's Hospital in Boston, MA, and Clinical Nursing Instructor at Boston College. Mary is a longtime friend, devoted mom, dedicated nurse and a true inspiration to us all. Mary breaks down the basics of keeping safe and healthy...we must Contain the Virus, so Please Stay Home! She talks about those most at risk, especially senior citizens and those with pre-existing conditions or are immuno-compromised. She mentioned her gratitude to those who are donating masks & gloves to nursing and hospital staff. -->Her advice for staying sane? Read a book, call a friend, FaceTime with your grandparents & relatives, limit the iPads & tv, and enjoy the outdoors (staying 6 ft away) but understand it’s 100% ok for kids to have screentime. During this time, we have to look for the silver lining in all of this, and how reconnecting with our families in the "old school" way is key. -->Welcome to the New Normal... homeschooling, social distancing (and social isolation), health risks, food/supply instability, closing businesses, financial crisis, economic downturn, working remotely (or in many cases, unemployment). -->We will use this safe space to support each other, stay positive, keep connected and share our creative ideas, thoughts, fears, frustrations...and hopefully turn everything around to to a positive and laugh a little in order to achieve "little victories" and "big wins" during this new and unsettling time. So join us and thank you for your support! -->DM us @hustleandheartpodcast if you would like to be our guest and Skype in! #DOTHEFIVE to Help stop Coronavirus (c/o WHO.org): 1) HANDS - Wash them often 2)ELBOW -Cough into it 3)FACE -Don't touch it 4) FEET - Stay more than 6ft apart 5) FEEL sick? STAY HOME...everyone should be staying home as is nationally mandated! #homeschool#coronavirus #covid19 #newnormal #keepsane #stayconnected #Selfquarentine #socialdistancing #donthoard #podcast #podcastlife #girlpower #womenwhorock #strongwomen #outbreak #justbreathe #stayhome #boston #unitedstates #pandemic #stayhome #bestrong #besafe #becreative #family #supporteachother #hustleandheart #hustleandheartpodcast #goingviral #goingviralpodcast #littlevictories #bigwins #financialcrisis #economicdownturn #WHO #CDC #Nurses

Does perioperative medicine alow institutions to take a broader view? Population health has been a theme on TopMedTalk, is it a logical extension of the perioperative process? How do we manage specialist care for the elderly and ensure high quality shared decision making? What lies behind the mindset change needed for some to accept surgery is not always the answer? Should we expect medical students to be taught the principles of perioperative medicine?   What are some of the unique tensions in the US system that can frustrate the adoption of a truly perioperative practice?    Presented by Desiree Chappell and Monty Mythen with their guest Angela Bader, Vice Chair of Perioperative Medicine at Brigham and Women's Hospital.   The British Journal of Anaesthesia article, which inspired this series, is here: https://bjanaesthesia.org/article/S0007-0912(20)30003-9/fulltext  

Host: Jennifer Caudle, DO Guest: Christopher Baugh, MD, MBA Although 6 million patients visit the Emergency Department every year with chest pain symptoms1, less than 4 percent of those visits lead to a diagnosis of acute myocardial infarction2. To address this gap, Dr. Jennifer Caudle is joined by Dr. Christopher Baugh, Vice Chair of Clinical Affairs at Brigham and Women's Hospital and Associate Professor at Harvard Medical School in Boston Massachusetts, who discusses the adoption of Elecsys Troponin T Gen 5 across the system's Emergency Departments. References U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. National Center for Health Statistics, https://www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2013_ed_web_tables.pdf (accessed February 27, 2020). Hsia, R.Y., Z. Hale and J.A. Tabas. (2016). A National Study of the Prevalence of Life-Threatening Diagnoses in Patients with Chest Pain. JAMA Internal Medicine 176(7):1029–1032.

Chelsey again speaks with Dr. Kaplan and Dr. Galetta, both practicing neurologists at Brigham and Women's Hospital and associated with Harvard Medical School. On this episode, they focus their discussion on postpartum considerations in NMOSD patients. They chat about topics that women living with NMO may experience immediately following giving birth. Questions covered: What do I need to know about breastfeeding? What do we know about treatment safety with breastfeeding? What about managing NMO symptoms postpartum? Postpartum depression? Who can provide support and help? Is NMO heritable?

Dr. Victor Nauffal, cardiology fellow at Brigham and Women's Hospital, is interviewed by Dr. David Wang about tachyarrhythmias. They work through a case and general approach to this topic, including a discussion about when to use electricity, distinguishing rhythms on an EKG, and treatment considerations. The case concludes with clinical pearls to take with you on the wards. https://www.runthelistpodcast.com/cardiology/#tachyarrhythmias Episode handout available here: http://bit.ly/RTL_tachyarrhythmias

Today's guest is Dr. Dennis Orgill, award-winning Professor of Surgery at Harvard University and Director of the Wound Care Center at Brigham and Women's Hospital in Boston.  Dr. Orgill recently reported an increase in the number of patients coming to the hospital with complications from cosmetic surgeries performed abroad. Medical tourism may seem like an inexpensive way to have certain procedures, but the complications can be very serious as well as costly.  Therese and Dr. Orgill discuss the problems observed in returning medical tourism patients.    Key Takeaways: Common procedures sought abroad include breast augmentation and abdominoplasty.  While foreign countries have many excellent cosmetic surgeons, some have no regulations and clinics are substandard in a number of ways. Medical tourism websites present very positive before and after images and the average patient is unaware of what safety standards govern a particular clinic. Infections, many highly resistant to antibiotics, and failure of wounds to heal, are the most common medical issues seen in returning patients in the Boston area.    "If you go outside the US, in many countries, they do not have the same infrastructure, the same quality control mechanisms that we have to assure safety." —  Dr. Dennis Orgill   Connect with Dr. Dennis Orgill: Brigham & Women’s Hospital Bio: Dennis Paul Orgill, MD, PhD        Connect with Therese: Website:   www.criticallyspeaking.net Twitter: @CritiSpeak Email: theresemarkow@criticallyspeaking.net     Audio production by Turnkey Podcast Productions. You're the expert. Your podcast will prove it.     

Suffolk County District Attorney Rachael Rollins joins Dan in studio to talk about the shooting at Brigham and Women's Hospital, the Grand Jury decision to not indict in the death of an Emerson College student, hate crimes in Boston, and much more.

Dr. Heather Hirsch, who leads the Menopause and Midlife Clinic at Brigham and Women's Hospital, breaks down what women should expect as they go through menopause. We discuss estrogen replacement therapy, hot flashes, changes in metabolism during menopause, and the Women's Health Initiative. Hirsch also explains how cognitive behavioral therapy can be beneficial when dealing with the symptoms that arise during the menopausal transition.

Authorities now say the suspect in a shooting at Brigham and Women's Hospital and pursuit down Route 9 earlier this month did not have an actual working firearm on him when he was shot and killed by police. WBZ NewsRadio's Karyn Regal reports.

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its 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, director of the Pauley Heart Center at BCU Health in                                                     Richmond, Virginia. Dr Carolyn Lam: So Greg, guess what? We are going to be discussing predicting the benefit of evolocumab therapy in patients with atherosclerotic disease using a genetic risk score. That's our featured paper this week coming from the results of the FOURIER trial. I bet you can't wait to discuss it, but I'm not going to let us until we talk about some of the papers in today's issue. Do you have one? Dr Greg Hundley: Yes, Carolyn, but first I'm going to get a cup of coffee because there's a lot of data in this one. This study is from the ODYSSEY trial and it involves alirocumab and it's from Dr Charles Paulding. Remember Carolyn, the ODYSSEY trial was a randomized double-blind placebo-controlled trial comparing alirocumab, a PCSK9 inhibitor or placebo in 18,924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. And the primary endpoint of this trial comprise death from coronary artery disease, non-fatal MI, ischemic stroke, or unstable angina requiring hospitalization. Now Carolyn, this is a sub-study and it was performed an A genome wide polygenic risk score for coronary artery disease comprising 6,579,025 genetic variants. And they were evaluated in 11,953 patients with available DNA samples. Analysis of the MACE risks, all those outcomes together, was performed in placebo treated patients while treatment benefit analysis was performed across all the patients. Dr Carolyn Lam: Ooh, so what did they find? Dr Greg Hundley: Well, Carolyn, both the absolute and relative reduction of MACE by alirocumab compared to placebo was greater in high versus low PRS patients. Those genetic, polygenetic risk scores combined in the patients. There was an absolute reduction by alirocumab in high versus low PRS groups of 6% and 1.5% respectively, and relative risk reduction in the alirocumab of 37% in the high PRS group versus 13% in the low PRS group. And so Carolyn, these results suggest the possibility of an independent tool for risk stratification using sort of precision medicine by selecting those using these genetic constructs, who may be more likely to benefit from this form of therapy. Dr Carolyn Lam: Wow Greg, that is really interesting. I genuinely think that our world is moving towards precision medicine and this really, really speaks to remember that feature paper also talking about genetic risk scores, but from the FOURIER trial. But before we get to that, I've got a basic science paper. Now this one provides insights into the mechanisms underlying age related hypertension. And it's from Dr Ying Yu and colleagues from Tianjin Medical University who hypothesize that since proinflammatory cytokines increase in T lymphocytes with aging and prostaglandin D2 suppresses T helper 1 cytokines through the D-prostanoid receptor 1, that this axis in T cells may play a role in age related hypertension. Dr Greg Hundley: Ah, Carolyn. What did they find in this study? Dr Carolyn Lam: Prostaglandin D2 biosynthesis and D-prostanoid receptor 1 expression, were both markedly decline in CD4 positive T cells from older humans and aged mice. D-prostanoid receptor 1 depletion in these CD4 positive T cells, exaggerated age dependent blood pressure elevation in mice by increasing tumor necrosis factor alpha and interferon gamma secretion. Whereas its over expression showed the opposite effect and its activation suppressed TH1 cytokines. These results really indicate that D-prostanoid receptor 1 and its downstream pathway may serve as an attractive immuno-therapeutic target for age dependent hypertension. Dr Greg Hundley: Oh wow. Very insightful Carolyn. Well, I've got a basic science paper to go over and it's from professor Kinya Otsu from Kings College London. This study addresses the mechanism of ongoing inflammation within the hearts of patients with cardiomyopathy. The study involves the assessment of Regnase-1 and RNAs involved in the degradation of a set of pro inflammatory cytokine messenger RNAs in immune cells. And the study involves the role of Regnase-1 in non-immune cells such as cardiomyocytes. Dr Carolyn Lam: Wow. Dr Greg Hundley: The degradation of cytokine messenger RNA by Regnase-1 and cardiomyocytes plays an important role in restraining sterile information in failing heart. Once the inflammatory cascade gets going, this is that constant inflammation that's ongoing. In addition, the Regnase-1 mediated pathway might be a therapeutic target to treat patients with heart failure as adeno-associated virus 9 mediated cardiomyocyte targeted gene delivery of Regnase-1 or administration of anti-IL-6 receptor antibody, attenuated the development cardiomyopathy induced by severe pressure overload in wild type mice. Dr Carolyn Lam: Wow, that's really interesting. I find this whole field of inflammation in heart failure of course, of key interest, but I'm going to next tell you about the results of the FUEL trial, which is the Fontan Udenafil Exercise Longitudinal trial. Dr Greg Hundley: Tell us about the Fontan operation. Dr Carolyn Lam: Aha, I thought you may ask, Greg. Well, the Fontan operation to remind us all, really creates a total cavopulmonary connection and a circulation in which the importance of pulmonary vascular resistance is therefore magnified. Over time, the circulation needs to deterioration of cardiovascular efficiency associated with a decline in exercise performance. This FUEL trial and reported this time by David Goldberg and colleagues from the Children's Hospital of Philadelphia was a phase 3 clinical trial, which randomized 400 patients with Fontan physiology from 30 sites in North America and the Republic of Korea. The participants were randomly assigned to Udenafil at 87.5 milligrams twice daily or placebo. And the primary outcome was the between group difference in change in oxygen consumption with peak exercise. Dr Greg Hundley: Hmmm, very large important trial it seems like Carolyn. What did they find? Dr Carolyn Lam: Treatment with Udenafil did not result in a significant increase in peak oxygen consumption, which was the primary outcome, but did result in improvements in measures of exercise performance at the anaerobic threshold, which was a secondary outcome. Udenafil was well tolerated with side effects limited to those previously known to be associated with phosphodiesterase type 5 inhibitors. These results and future perspectives are discussed an editorial called FUELing the Search for Medical Therapies in Late Fontan Failure, by Doctors Gewillig and De Bruaene. Dr Greg Hundley: Very nice, Carolyn. Now how about the rest of the journal? Dr Carolyn Lam: Oh well I want to tell you about this in-depth review by Dr Rosenkranz and it's entitled, Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure. Very intriguingly, talking about non-cardiac features, as well as cardiac, of right heart failure, a real, real must read with beautiful figures. In the cardiovascular case series we discuss a case of left ventricular non-compaction and cardiogenic shock by Dr Shenoy. There are also two research letters I want to tell you about one by Dr Gillinov on the accuracy of the Apple watch for detection of atrial fibrillation. And this time looking at the Apple watch series 4, which interestingly employs electrodes to generate a single lead ECG and provides two mechanisms for rhythm assessment. Won't tell you more. You got to pick up this beautiful letter. The next is by Dr Mazer on the effect of empagliflozin on erythropoietin levels IN stores and red blood cell morphology in patients with type II diabetes and coronary artery disease. And this really provides evidence to suggest that SGLT 2 inhibition with empagliflozin may stimulate erythropoiesis via an early increase in erythropoietin production in people with diabetes. Dr Greg Hundley: You know Carolyn, we just keep hearing more about EMPA and DAPA and they are just going to really pave the way I think for a whole new class of agents that we're going to be using frequently. I've got a couple letters in the mailbox and one is by Sugimoto and Taniguchi regarding the article, Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients with Implantable Cardio Defibrillators, a randomized clinical trial. And then also there's another research letter by Dr Hiroshi Sugimoto from Kobe Red Cross Hospital with a response by Jakob Lüker from University of Cologne. What a great issue. How about we proceed to that feature article? Dr Carolyn Lam: You bet. Can a genetic risk score identify individuals who will derive greater benefit from PC SK9 inhibition? Well guess what? We're going to find out now in our feature discussion. So pleased to have with us the first and the corresponding authors of our feature paper, Dr Nicholas Marston and Dr Christian Ruff, both from the TIMI study group in Brigham and Women's Hospital and Harvard Medical School and also to have our lovely associate editor, Dr Svati Shah from Duke University in Durham, North Carolina. Welcome everyone. Nick, could I get you started with telling us about this exciting analysis that you did from the FOURIER trial? Dr Nicholas Marston: The FOURIER trial was a 27,000 patient cardiovascular outcomes trial that studied the PC SK9 inhibitor, evolocumab and it demonstrated a significant reduction in major adverse cardiovascular events in patients who had established atherosclerotic disease. And in the study, there was a 15% relative risk reduction and a 2% absolute risk reduction, which earned it a class 2 recommendation for very high-risk patients with atherosclerosis in the recent cholesterol management guidelines. And what we've done in previous lipid trials is we studied the interactions between genetic risk and treatment benefit. For example, in 2015 we showed that patients with high genetic risk, those in the top 20% of genetic risk, had the greatest benefit from statin therapy in terms of both absolute and relative risk reductions. And so now we have the opportunity with evolocumab and data from the FOURIER trial to ask the same question of PC SK9 inhibitor. That is, could a genetic risk score identify patients who will drive a greater treatment benefit and we hypothesize that like statins, there would in fact be a significant interaction between genetic risk and therapeutic benefit. Dr Carolyn Lam: That's so cool Nick. But could I ask, the question always comes, is it nature versus nurture? And so I really love the way that you dealt with the clinical risk factors as well. Could you maybe walk us through that and then tell us the results? Dr Nicholas Marston: Yes, absolutely. We for this study, kind of had two objectives. One was to look at risk prediction and then the other look at treatment benefit and using a genetic risk score for both. However, we wanted to go further than just use the genetic risk score. We wanted to incorporate clinical risk factors since that's how we would do it as physicians in the clinic. We would have not just genetic risk data in front of us but also clinical data. And so when we were grading a patient's risk using genetic risk, we also factored in if they had multiple clinical risk factors. And what we found by combining both genetic and clinical risk was that there was a significant gradient of risk across these risk categories. That is patients who were without high genetic risk and without multiple clinical risk factors actually had no benefit from evolocumab over the 2.2-year follow-up period. However, those without high genetic risk, but who did have multiple clinical risk factors, derived an intermediate benefit. About a 13% relative risk reduction and 1.4% absolute risk reduction. And then it was the high genetic risk group, independent of whether or not they had multiple clinical risk factors that had the largest benefit from evolocumab with a relative risk reduction of 31%, absolute risk reduction of 4% and the number needed to treat of 25. And that's actually a twofold greater benefit than was seen in the overall FOURIER trial population. Dr Carolyn Lam: That's really stunning results. Now I know Svati's going to have questions for us, so maybe I should invite you Svati, just put these results into context and let the audience know what we were thinking as editors when we saw this brilliant paper. Dr Svati Shah: Yeah, thanks Carolyn. And I think Nick has done a fantastic job of describing the exciting results from this paper and just kind of taking a step back to help the audience understand what we're talking about when we're talking about genetics. For decades, we've been trying to figure out the genetics of heart disease and we're not talking about the genetics of things that are really rare like long QT syndrome, but the genetics of just common complex heart diseases. And amongst the scientific community, we've tried all different ways of sort of analyzing these data and so I want to make sure that everybody who's listening understands the novelty of really looking at these polygenic risk scores. Where we have now come to understand that it's not a single gene, it's not even two genes, that it's multiple variants and multiple genes and when they're combined, that's when you really have the power to understand how it might be useful in terms of how we take care of patients. Really important with how Nick and Christian have laid out this really nice paper as well as their prior work in statins, is that not only did they show that these polygenic risk scores are associated with cardiovascular outcomes or even different amongst whether you get treated with the drug or whether you don't, but really importantly they're getting it clinical utility, not only with regards to showing that they compare it to a clinical risk score, but really showing that if you use these polygenic risk scores, you can identify patients who may derive the greatest benefit from PC SK9 inhibitors. And importantly in their paper, they show that if you have low polygenic risk score and low clinical risk score, you may not derive benefit from PC SK9 inhibitors. With all the caveats that this is a secondary prevention population, so I really applaud Christian and Nick and his team for the nice work that was done. Dr Carolyn Lam: Oh, couldn't agree more, Svati. You know what I was very struck with too, because some people go, I may have a genetic risk. Maybe I could undo it or somehow overcome it with my clinical risk factors. And that's why I really appreciated that they showed that it was additive, and genetics still matter even if you have risk factors and vice versa. That was really cool. Christian, could I ask you to maybe describe a bit, what kind of genetic risk score this was and maybe perhaps point out some of the limitations therefore of what you studied. Dr Christian Ruff: As Svati mentioned, this is really a quickly evolving field. We now have the ability to either genotype or sequence all of the variation that makes us different from one another. Our susceptibility to disease as well as our potential benefit for treatment. We had for this study, looked at several different risk scores. The one we focused on was a coronary artery disease genetic risk score that had 27 different variants that had been shown to predict having a cardiac event, both in primary and secondary populations. And we have previously identified patients who may have been at a higher risk who received greater benefit from statin therapy. And in this study, we actually compared this 27 variant genetic risk score with actually a much larger score of over six million variants. And interestingly, the two scores performed fairly similar with respect for risk prediction. One of the big questions going forward is, we have lots of ways to develop genetic risk scores, how many different variants do we need? What more information do we have with more complicated scores? And I think Svati really hit on a really critical point is that really this study is really layering in genetic risk on top of clinical risk factors, which we can easily assess at the bedside. And I think what's reassuring to patients is that not only is genetic risk able to give us much more information for prognosis, but that this risk is modifiable. People think that their genetic risk, they're sort of born with it and there's nothing that they can do about it. But in this study, as Nick pointed out, even over a very short period of time with powerful lipid lowering therapy with a PC SK9 inhibitor, we essentially reduced these patients at high genetic risk to the risk of the very low risk patients on placebo. I think this is a reassuring message that genetics plays an important role for risk prediction and it identifies patients who we might target for more intensive therapy and that we can potentially reduce that risk even though that risk is based on the DNA that they're born with. Dr Carolyn Lam: Indeed. That's a great point. And Svati, I'm sure you were thinking along those lines when you invited that beautiful editorial by Doctors Daniel Raider and Michael Levin. But Svati, would you like to comment on your thoughts on, is this ready for prime time? Dr Svati Shah: I think that's the key question. What Christian and Nick and his team have done is take us a big step forward in how we use these polygenic risk scores. I think there still are many skeptics amongst the genetic scientific community about, well great, you can look at 27 variants and some of these polygenic risk scores, you're looking at a million things. How do we actually use that to take care of patients? I actually want to turn this back, that question back around Carolyn, and I'd like to ask Christian next, what are the next steps? There are a lot of cardiologists who if you're listening to this podcast, should we all run out and get our patient's genotype to order this genetic chip so that we can figure out what their polygenic risk score is? Dr Christian Ruff: Yeah, that's a great question and I could start off and then hand off to Nick, but I think one of the key questions is obviously there are a lot of genetic risk scores and I don't think as a field that we've come up with which one we really should implement in clinical practice. There's still a lot of fine tuning and figuring out which score gives us the most amount of useful information. And then I think as something that you had mentioned that these scores are generated in both a healthy cohort population and now, we're looking at it in clinical trials and there's no sort of reference. Like when we have a blood test and we say, "If your hemoglobin A1C is above or below this number that means that you have diabetes." And we haven't figured out, what are the actual thresholds that you use for these genetic risk scores that you can implement broadly across different patient populations. There's still a lot of work that needs to be done to make these scores ready for prime time. This is really setting the stage. Is this something that we should be doing? And I think these studies and others say that the data looks great that we should be doing this, but we haven't yet figured out the logistics of which score and how do we actually reference to population. Dr Nicholas Marston: Yeah, I agree with Christian definitely that we need to figure out what's the optimal genetic risk tool and for which population and what the cut points are. And then I think another piece that's going to be very important moving forward is doing a lot of this work and studying in non-European ancestry and cohorts and populations. Because most of the work done so far in discovery has been in databases such as the UK Biobank. And that limits us in our analyses to European ancestry patients. And so, I think for this to go to prime time, we want to be able to offer it to all of our patients. And so that means making sure we have scores that fit all populations, not just primary and secondary, but also all different types of ancestry. Dr Carolyn Lam: Oh, I'm so glad you mentioned that, Nick. That was exactly on my mind coming from Asia. And the other thing of course, would be cost effectiveness of these approaches. Oh my goodness. I wish we had all the time in the world to talk about this more. The implications are enormous, but just let me thank you on behalf of all of us for publishing this remarkable paper in Circulation. Audience, you've been listening to Circulation on the Run. Don't forget to tune in again next week. Dr Greg Hundley: This program is copyright, the American Heart Association 2020.