Podcasts about ottawa heart institute

Recorded live at the Critical Care Canada Forum 2024, this episode is part of our special Cardiac ICU Series.Dr. Rebecca Mathew, cardiologist and critical care specialist at the University of Ottawa Heart Institute, joins us to discuss the latest refractory cardiac arrest practice updates, including antiarrhythmic drugs, defibrillation strategies, and the role of ECPR.Chapters: • Defining refractory cardiac arrest • Antiarrhythmic drugs: amiodarone vs. lidocaine • Defibrillation strategies: vector change and double sequential defibrillation • Emerging therapies: stellate ganglion blocks and electrical storm management • ECPR: who qualifies and what the trials say • Equity and feasibility challenges in cardiac arrest management • ICU recovery clinics and patient-centered outcomes • Clinical trials: barriers to enrollment and the need for changeReferences: 1. ROC ALPS Trial: 1. Kudenchuk PJ, Brown SP, Daya M, et al. Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and Methodology Behind an Out-of-Hospital Cardiac Arrest Antiarrhythmic Drug Trial. American Heart Journal. 2014;167(5):653-9.e4. doi:10.1016/j.ahj.2014.02.010. PMID: 24766974.[1] 2. DOSE VF: Cheskes S, Drennan IR, Turner L, Pandit SV, Dorian P. The Impact of Alternate Defibrillation Strategies on Shock-Refractory and Recurrent Ventricular Fibrillation: A Secondary Analysis of the DOSE VF Cluster Randomized Controlled Trial. Resuscitation. 2024;198:110186. doi:10.1016/j.resuscitation.2024.110186. PMID: 38522736 3. ARREST: Yannopoulos D, Bartos J, Raveendran G, et al. Advanced Reperfusion Strategies for Patients With Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation (ARREST): A Phase 2, Single Centre, Open-Label, Randomised Controlled Trial. Lancet (London, England). 2020;396(10265):1807-1816. doi:10.1016/S0140-6736(20)32338-2. PMID: 33197396 4. INCEPTION: Ubben JFH, Suverein MM, Delnoij TSR, et al. Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest - A Pre-Planned Per-Protocol Analysis of the INCEPTION-trial. Resuscitation. 2024;194:110033. doi:10.1016/j.resuscitation.2023.110033. PMID: 37923112 Disclaimer:This episode is for educational purposes only and does not constitute medical advice. The views expressed are those of the hosts and guests and do not necessarily reflect their employers.

Anastasia Fahlman and Sarah Damiani from the University of Ottawa speak with Dr. Erin Mulvihill, Scientist and Director of the Energy Substrate Metabolism Research Laboratory at the University of Ottawa Heart Institute. Tune in to learn more about her recent work published in CellPress, which explores the potential mechanisms underlying the cardioprotective benefits of metabolic surgery and GLP-1RA-based therapies. It also discusses recent evidence and emerging therapies in this dynamic area of research. Learn more: https://www.sciencedirect.com/science/article/pii/S1043276024001930                                                                     Credits for music: Soundtracks by the Underground Drive. All rights reserved. Listen more: https://music.apple.com/ca/artist/the-underground-drive/1571062779https://open.spotify.com/artist/4sCJG8TMQyTZ9FDd1JjJmRPodcast by Sarah Damiani (Voice, Producer, Show Co-Host, Writer Editor, Audio Master) and Anastasia Fahlman (Voice, Show Co-Host, Writer Editor, Audio Master)

As part of the BEaTS Research Radio Translational and Molecular Medicine Sci-Comm Podcast series, our host, Daniel Anderson, interviews Dr. Ruel and NP Ponnambalam. In this episode, Daniel, Dr. Ruel, and Ms. Ponnambalam discuss the promise of minimally invasive coronary bypass grafting (MICS CABG) and how it is a less invasive and safer option for patients who require coronary bypass surgery. Dr. Marc Ruel (MD, MPH) is the endowed chair of minimally invasive cardiac research at the University of Ottawa Heart Institute. He is also a Professor in the Division of Cardiac Surgery at the University of Ottawa Heart Institute. He is a Professor in the Department of Surgery and Department of Cellular and Molecular Medicine at the University of Ottawa. Menaka Ponnambalam (RN-EC, MN, NP-Adult) is a nurse practitioner in the Division of Cardiac Surgery at the University of Ottawa Heart Institute. Learn moreDr. Marc Ruel: https://www.ottawaheart.ca/profile/ruel-marcMenaka Ponnabalam: https://www.ottawaheart.ca/patients-and-visitors/clinical-departments/cardiac-surgery0:20 | Introduction to Dr. Marc Ruel & NP Menaka Ponnambalam1:22  | Origin of the MICS CABG Procedure4:39  | Patient Experience6:35  | Science Behind the Magic 8:20  | Future of Cardiac Surgery9:05  | Teamwork10:16  | Patient Advice13:29  | Conclusion & ResourcesMusic: Waltz in F# minor by Josh Zeldin & Huy K. Nguyen (unpublished composition). All rights reserved.Huy K. Nguyen (Producer), Daniel Anderson (Host), Josh Zeldin (Writer), Gil Toex (Editor) 

We all know that walking is hugely beneficial for our health and wellbeing, but we can get even fitter, and use nearly twice as many muscles, by introducing some poles and a simple technique. Join Michael Mosley as he delves into the science of Nordic walking to find out how it can enhance our walks by burning more calories and helping to ease back pain. He speaks to Dr Jennifer Reed from the University of Ottawa Heart Institute about her research, which has demonstrated why Nordic walking is one of the best forms of exercise for improving your heart health. Our volunteer Jessica picks up some poles and transforms her regular walks into a full-body workout. Series Producer: Nija Dalal-Small Editor: Zoë Heron A BBC Studios production for BBC Sounds / BBC Radio 4.

#22 Guest, Cody McKay, shares his journey with an ascending aortic aneurysm and how it impacted his life as a young athlete. He discusses the importance of considering cardiac health and the effects it can have on sports and overall well-being. Cody highlights the need for awareness and support for individuals dealing with heart conditions, emphasizing that age and athleticism are not exempt from such issues. He is also an advocate for heart-healthy living and the importance of educating oneself on baseline measurements like blood pressure. Cody's inspiring story serves as a reminder that even with a diagnosis, one can still live a full life and pursue their dreams. Plus, he sheds light on his efforts to raise awareness and support for Project Heart.If you are looking for something specific - here's where you'll find it:[03:50] At 29, chest X-ray found heart abnormality.[06:10] Shortness of breath, frustration, tests, aortic aneurysm.[10:46] CT confirms ascending aortic aneurysm.[15:21] Managing an aneurysm, achieving biking milestones.[16:24] Living with medically managed aneurysm, still active.[19:36] Different situations, years of sport training. Heart rate, intensity, energy systems, max threshold. Ceiling of 140-150 for comfort.[23:24] Cody's outlook - possible reduced quality of life, chance of failure. Good odds currently. Long-lasting valve, no need to replace. Simplified procedure for aortic aneurysm.[26:17] Wheelchair to walking: Cody's journey after surgery.[36:31] Project Heart and paying it forward.A Little More About Today's GuestCody McKay is a 32-year-old male who is a policy analyst by day, and competitive-elite cyclist at all other times. Following his ascending aortic aneurysm diagnosis, subsequent open heart surgery, and now return to sport, he is riding and racing to raise awareness about heart & cardiovascular disease, prove that individuals who have been impacted by these diseases can achieve great things, and raise funds for the University of Ottawa Heart Institute, Canada's largest cardiac centre.How to connect with CodyInstagram: @cardiac_cody**I am not a doctor and this is not medical advice. Be sure to check in with your care team about all the next right steps for you and your heart.**How to connect with BootsEmail: Boots@theheartchamberpodcast.comInstagram: @openheartsurgerywithboots or @boots.knightonLinkedIn: linkedin.com/in/boots-knightonBoots KnightonIf you enjoyed this episode, take a minute and share it with someone you know who will find value in it as well. You can share directly from this platform or send them to:Open Heart Surgery with Boots

Dr. Marc Ruel, a heart surgeon at the University of Ottawa Heart Institute and professor in the department of surgery, University of Ottawa Learn more about your ad choices. Visit megaphone.fm/adchoices

In episode 9, we welcome Dr. Thais Coutinho, cardiologist and division head of Prevention and Rehabilitation at the University of Ottawa Heart Institute, as well as Associate Professor of Medicine at the University of Ottawa. Additionally, Dr. Coutinho sits as the chair of the Heart Institute's Canadian Women's Heart Health Centre, and is an internationally recognized clinician scientist in the field of arterial health.  We discuss her calling to medicine, work-life balance, scope of practice, and future goals. Dr. Coutinho also offers some insight in regard to the mitigation of risks associated with arterial diseases in women, as well as the unspoken realities of her professional domain. She further provides an overview of the utilization of her grant from the Public Health Agency of Canada (PHAC). The views expressed in this podcast belong solely to the speakers and do not necessarily reflect any institution/associations they are affiliated with.  This podcast should not be considered a substitute for medical advice. Ottawa Heart Institute - Women's heart health: https://foundation.ottawaheart.ca/?gclid=CjwKCAjwge2iBhBBEiwAfXDBRwZARPv_Y6i0GlXRPyQ2j3YuAOmvXknvCcoA0lQX8IbKtF8TQ7YvthoCAlcQAvD_BwE  Women's Cardiac and Cerebrovascular Health Committee (WCCH) with FMWC: https://fmwc.ca/advocacy/advocacy-wcch/

Is inflammation the driving force for diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF)? In this episode, Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews author Dr. Thassio Mesquita (Cedars-Sinai Medical Center) and expert Dr. Darryl Davis (University of Ottawa Heart Institute) about the research by de Couto et al. Using a Dahl salt-sensitive rat model of HFpEF, the authors delivered cardiosphere-derived cells (CDCs) via intracoronary injection into the microcirculation. After 2 weeks of treatment with CDCs, the hypertensive rats showed improved endothelial-dependent vasodilation, reduced oxidative stress, restored expression of endothelial nitric oxide synthase, and reduced inflammation. Overall, the authors found that CDCs made significant improvements in the cardiovascular health of hypertensive rats with HFpEF. What is the therapeutic potential of cardiosphere-derived cells for treating heart failure with preserved ejection fraction (HFpEF)? Listen and learn more.   Geoffrey de Couto, Thassio Mesquita, Xiaokang Wu, Alex Rajewski, Feng Huang, Akbarshakh Akhmerov, Na Na, Di Wu, Yizhou Wang, Liang Li, My Tran, Peter Kilfoil, Eugenio Cingolani, and Eduardo Marbán Cell therapy attenuates endothelial dysfunction in hypertensive rats with heart failure and preserved ejection fraction Am J Physiol Heart Circ Physiol, published October 17, 2022. DOI: 10.1152/ajpheart.00287.2022

“Culture is the accumulation of smaller moments.” - Keira Torkko What IS organizational culture? What are all the components and how do you create the culture you want? These are complex questions - and yet they are critical to the work of Talent Leaders. Listen to this episode for insights on building and sustaining culture. My guest is Keira Torkko who is Chief People Officer at Assent in Ottawa, Ontario, Canada. Keira has an intriguing background in that she did not spend the majority of her career in HR. She holds a B. Comm and is a CGA, and has led Employee Experience and People for the last 4 years. In this episode of Talent Management Truths, you'll discover:

This month on Episode 34 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the March 4 and March 18th issues of Circulation Research. This episode also features a conversation with Dr Mireille Ouimet and Sabrina Robichaud from the University of Ottawa Heart Institute to discuss their study, Autophagy is Differentially Regulated in Leukocyte and Non-Leukocyte Foam Cells During Atherosclerosis.   Article highlights:   Pauza, et al. GLP1R in CB Suppress Chemoreflex-Mediated SNA   Lim, et al. IL11 in Marfan Syndrome   Hohl, et al. Renal Denervation Prevents Atrial Remodeling in CKD   Liu, et al. Smooth Muscle Cell YAP Promotes Arterial Stiffness   Cindy St. Hilaire:        Hi and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to be highlighting articles from our March issues of Circulation Research. I'm also going to speak with Dr Mireille Ouimet and Sabrina Robichaud from the University of Ottawa Heart Institute, and they're with me to discuss their study, Autophagy is Differentially Regulated in Leukocyte and Non-Leukocyte Foam Cells During Atherosclerosis.   The first article I want to share is titled GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition. The first author is Audrys Pauza, and the corresponding authors are Julian Paton and David Murphy at the University of Bristol.   Cindy St. Hilaire:        Hypertension and diabetes are risk factors for cardiovascular disease. And yet, for many patients with these two conditions, lowering blood pressure and blood sugar is insufficient for eliminating the risk. The carotid body is a cluster of sensory cells in the carotid artery, and it regulates sympathetic nerve activity. Because hypertension and diabetes are linked to increased sympathetic nerve activation, this group investigated the role of the carotid body in these disease states. They performed a transcriptome analysis of crowded body tissue, from rats with and without spontaneous hypertension. And they found among many differentially-expressed genes that the transcript encoding glucagon-like peptide-1 receptor or GLP1R, was considerably less abundant in hypertensive animals.   Cindy St. Hilaire:        This was of particular interest because the gut hormone GLP-1 promotes insulin secretion and tends to be suppressed in Type 2 diabetes. Moreover, GLP1R agonists are already used as diabetic treatments. This group showed that treating rat carotid body with GLP1R agonist suppresses sympathetic nerve activation and arterial blood pressure, suggesting that these drugs may provide benefits in more than one way. Perhaps the carotid body could be a novel target for lowering cardiovascular disease risk in metabolic syndrome.   Cindy St. Hilaire:        The second article I want to share is titled Inhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan syndrome. The first author is Wei-Wen Lim, and the corresponding author is Stuart Cook and they're from the National Heart Center in Singapore. People with the genetic connective tissue disorder Marfan syndrome, are typically tall and thin with long limbs and are prone to skeletal, eye and cardiovascular problems, including a life-threatening weakening of the aorta. While Marfan syndrome patients commonly take blood pressure-lowering treatments to minimize risk of aortic aneurysm and dissection, there's currently no cure for Marfan syndrome or targeted therapy.   Cindy St. Hilaire:        The cytokine IL11 is strongly induced in vascular smooth muscle cells upon treatment with the growth factor TGF-beta, which is over activated in Marfan syndrome patients. And TGF-beta is also considered a key feature of the syndrome's molecular pathology. This study found that IL11 is strongly upregulated in the aortas of Marfan syndrome model mouse, and that genetically eliminating IL11 in these animals protected them against aortic dilation, fibrosis, inflammation, elastin degradation and loss of smooth muscle cells. Treating Marfan syndrome mice with anti-IL11 neutralizing antibodies exhibited the same beneficial effects. These results suggest that perhaps inhibiting IL11's activity could be a novel approach for protecting the aortas of Marfan syndrome patients.   Cindy St. Hilaire:        The next article I want to mention is titled Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in Chronic Kidney Disease. The first authors are, Mathias Hohl, Simina-Ramona Selejan and Jan Wintrich, and the corresponding authors also Mathias Hohl, and they're from Saarland University. People with chronic kidney disease have a two to three fold higher risk than the general population of developing atrial fibrillation, which is a common form of arrhythmia that can be life-threatening. Chronic kidney disease is associated with activation of the sympathetic nervous system, which can be damaging to the heart. Thus, this group examined myocardial tissues from atrial fibrillation patients with and without chronic kidney disease to see how they differ. They found that atrial fibrosis was more pronounced in patients with both conditions than in patients with atrial fibrillation alone, suggesting that chronic kidney disease perhaps exacerbates or even drives arterial remodeling.   Cindy St. Hilaire:        Sure enough, induction of chronic kidney disease in rats led to greater atrial fibrosis and incidence of atrial fibrillation than seen in the control animals. Renal denervation is a treatment in which the sympathetic nerves are ablated, and it's a medical procedure that's used for treating uncontrolled hypertension, and it has also been shown in animals to reduce atrial fibrillation. Performing renal denervation in the rats with chronic kidney disease reduced atrial fibrosis and atrial fibrillation susceptibility. This study not only shows that chronic kidney disease induces atrial fibrosis and in turn atrial fibrillation, but also suggests that renal denervation may be used in chronic kidney disease patients to break this pathological link and prevent potentially deadly arrhythmias.   Cindy St. Hilaire:        The last article I want to highlight is titled YAP Targets the TGFβ Pathway to Mediate High-Fat/High-Sucrose Diet-Induced Arterial Stiffness. First author is Yanan Liu and the corresponding author is Ding Ai from Tianjin Medical University. Metabolic syndrome is characterized as a collection of conditions that increase the risk of cardiovascular diseases, such as obesity, hypertension and diabetes. Among the tissue pathologies associated with metabolic syndrome is arterial stiffness, which itself is a predictor of cardiovascular disease incidence and mortality. To specifically investigate how arterial stiffness develops in metabolic syndrome, this group fed mice a high-fat, high-sugar diet, which is known to induce metabolic syndrome and concomitant arterial stiffness.   Cindy St. Hilaire:        After two weeks on the diet, the animals' aorta has exhibited significant upregulation of TGF-beta signaling, which is a pathway known for its role in tissue fibrosis, and the aorta has also exhibited increased levels of yes-associated protein, or YAP, which has previously been implicated in vascular remodeling, collagen deposition and inflammation. YAP gain and loss of function experiments in transgenic mice revealed that while knockdown of protein in the animals' smooth muscle cells attenuated arterial stiffness, increased expression exacerbated the condition.   Cindy St. Hilaire:        The team went on to show that YAP interacted with and prevented the activation of PPM-1 B, which is a phosphatase that normally inhibits TGF-beta signaling and thus fibrosis. Together the results suggest that targeting the YAP, PPM-1 B pathway, could be a strategy for reducing arterial stiffness and associated cardiovascular disease risk in metabolic syndrome.   Cindy St. Hilaire:        Today, Sabrina Robichaud and Dr Mireille Ouimet from University of Ottawa Heart Institute are with me to discuss their study Autophagy is Differentially Regulated in Leukocyte and Non-Leukocyte Foam Cells During Atherosclerosis, which is in our March 18 issue of Circulation Research. So thank you both for joining me today.   Sabrina Robichaud:    Thank you so much for having us. It's a pleasure.   Mireille Ouimet:         Thank you for having us.   Cindy St. Hilaire:        Yeah, and congrats on the study. So we know that LDL particles contain cholesterol and fats, and these are the initiating factors in atherosclerosis. And it's also really now appreciated that inflammation in the vessel wall is a secondary consequence to this lipid accumulation. Macrophages are an immune cell that, in the context of the plaque, gobble up this cholesterol to the point that they become laden with lipids and exhibit this foamy appearance, which we now call foam cells. And these foam cells can exhibit atheroprotective properties, one of them called reverse cholesterol transport, and that's really one of the focuses of your paper. So before we dig into what your paper is all about, could you give us a little bit of background about what reverse cholesterol transport is in the context of the atherosclerotic plaque? And maybe introduce how it links to this cellular recycling program, autophagy, which is also a big feature of your study.   Mireille Ouimet:         Yes, so the reverse cholesterol transport pathway is a pathway that's very highly anti-atherogenic. It's linked to HDL function and the HDL protective effects, in that HDL can serve as a cholesterol acceptor for any excess cholesterol from arterial cells or other cells of the body and return this excess cholesterol to the liver for excretion into the feces. There is also trans-intestinal cholesterol efflux that can help eliminate any excess bodily cholesterol. Mireille Ouimet:         So reverse cholesterol transport is a way that we can eliminate excess cholesterol from foam cells in the vascular wall, and that's why we're really interested in the process. But the rate-limiting step of cholesterol efflux out of foam cells in plaques is actually, they have to be mobilized in the form of free cholesterol to be pumped out of the cells through the action of the ATP-binding cassette transporters. And so the rate-limiting step of the process is the hydrolysis of the cholesterol esters and the lipid droplets, because that's where the excess cholesterol is stored in foam cells.   Mireille Ouimet:         And so for years, people investigated the actions of cytosol like lipases in mobilizing free cholesterol from lipid droplets, although the identity of those lipases are not well-known and in macrophage themselves, but our recent work showed a role for autophagy in the catabolism of lipid droplets. And in fact, in macrophage foam cells, 50% of lipid droplet hydrolysis is attributable to autophagy while the other half is mediated by neutral lipases, which makes it really important to investigate the mechanisms of autophagy-mediated lipid droplet catabolism.   Cindy St. Hilaire:        That is so interesting. I guess I didn't realize it was that significant a component in that kind of rate-limiting step. That's so cool. So really, a lot of the cholesterol efflux studies, and maybe this is just limited to my knowledge of a lot of these cholesterol efflux studies, but to my knowledge, it's been really focused on the foam cell itself, the macrophage foam cell. However, there's been a lot of recent work that has now implicated vascular smooth muscle cells in this process. So could you share some of the research specific to smooth muscle cells and smooth muscle-derived foam cells that led you to want to investigate the contributions of smooth muscle cell-derived foam cells in cholesterol efflux?   Mireille Ouimet:         Yeah, so you're right in the sense that macrophages have always been the culprit foam cells in the atherosclerotic plaques but pioneering work from several groups, including Edward Fisher and Gordon Francis, they've shown that the smooth muscle cells can actually acquire a macrophage-like phenotype becoming lipid-loaded and foamy. And there's been work specifically looking at the ABC transporters, and their ability to efflux cholesterol from these vascular smooth muscle cell-derived foam cells, because as they trans-differentiate into macrophage-like cells, they acquire the expression of ABCA1, but this is to a lower extent, as compared to their macrophage counterparts.   Mireille Ouimet:         And the efflux is defective because there's an impairment in liposomal cholesterol processing of the lipoproteins that's really important to activate a like cell, and the expression of the ABC transporters, so vascular smooth muscle cell-derived foam cells are very poor effluxes.   Sabrina Robichaud:    There's very few studies that look at the vascular smooth muscle cell foam cells, and the very few that did look at it mostly focused on the ABCA1 transporters, and did show that they were poor effluxes. And as we all know, ABC1 is not the only cholesterol transporters that can transport cholesterol out of cells, there's also ABCG1 which is also one of our major findings in our paper.   Cindy St. Hilaire:        Can you tell us a little bit about the models you chose in the study and why you picked them? And also maybe a step back in terms of, what are the pros and cons of using mouse models in atherosclerotic studies?   Sabrina Robichaud:    So we chose to use the GFP-LC3 reporter mouse model because it allows us to track in lifestyle the movement of LC3, which is the main component of the autophagosome which is involved in pathology. So by using this reporter model, we could infer whether or not the cells had high autophagy or low autophagy. And to induce atherosclerosis in these mice, instead of backcrossing them to either an LDLR knockout or an ApoE knockout, we chose to do the adeno-associated virus that encode the gain of function PCSK9 instead to kind of minimize the time for breeding. It did have the effect that we needed in terms of raising plasma cholesterol to induce the atherosclerosis. So that was one of the models that we used in our paper.   Mireille Ouimet:          There's not very many good mouse models to study autophagy flux in vivo and GFP-LC3 is kind of the main one currently. We're working on developing some other tools to track lipophagy in vivo, but these things take time to put in place. So in the future, we hope to have some better tools to track lipophagy in real-time in vivo.   Cindy St. Hilaire:        How difficult is it to measure autophagy flux in vivo? I know there's certain part like LC3 or P62, a lot of people use a western blot and it's like, oh, it's high, it must be active, but it's a flux. So it's a little bit more... There's more subtleties to that, dynamic than that. So how difficult is it to really measure this flux in in vivo tissues?   Mireille Ouimet:         Yes, so now there are more recent mouse models that have been developed more recently to replace kind of the GFP-LC3 is the Rosella LC3. So it has both a red and a green tag, and so two LC3, so when autophagosomes are fused to lysosomes and are degraded, then there's preferential quenching of the GFP first, and then you have the red appearance that predominates so we know that then it's kind of like it a live flux measurements. Because we use the GFP-LC3 mouse, Sabrina treated her cells ex vivo. When we dissected out the aortic arches, digested the cells then we divided those into two components and added bafilomycin so that we can inhibit lysosome acidification to see the changes in the flux. And that's really to get the differences in untreated versus bafilomycin-treated.   Mireille Ouimet:         When we inhibit the lysosome, then we're sure that it is a functional flux or not. But it's kind of an indirect way of measuring it, and it reads very complex when we're talking about P62 and LC3 degradation with or without lysosome inhibition, but you really need that lysosomal inhibition, to show that if you block the degradation of the autophagosomes that fuse in with a lysosome, then you get an increase in the LC3 and the P62, and that's when you know that the flux is you intact.   Mireille Ouimet:         Because you could get an increase in LC3, that's just related to a defect in the breakdown of the autophagosome. But in our study, we've used phosphorylated ATG16L1, which is a now better marker of active autophagy. And I would recommend researchers to begin to use that rather than the combination of P62 and LC3 together with or without a lysosome inhibitors such as- Cindy St. Hilaire:        Oh, interesting. So let's repeat that, phosphorylated ATG-   Mireille Ouimet:         16L1, yes. So there's been an antibody that was developed by a colleague at the University of Ottawa, Dr Ryan Russell, and it's commercially available through cell signaling now, and it really has been a great tool to track active autophagy.   Cindy St. Hilaire:        That's great. I remember my lab was looking at that at one point, and I was trying to explain the flux as... I don't know if people are going to remember this, but there's this amazing, I Love Lucy skit, where her and Ethel are working on a chocolate factory conveyor belt, and it picks up speed. And because she can't get it all done quick, she starts stuffing them in her mouth. And it's like, if you just took a snapshot of that, you would not know whether it's going too fast, or not functioning properly. And so I equate the flux experiments to that. Which are probably aging myself a lot on so.   Cindy St. Hilaire:        All right, so sticking to kind of the autophagy angle, what were the differences you found in autophagy in early and late atherosclerotic plaques? Because I know you looked at those two time points, but also, importantly, between the macrophage foam cells and the smooth muscle cell-derived foam cells?   Sabrina Robichaud:    So surprisingly, there weren't that big of a difference between each time point when we were looking at the individual cell type by themselves. Surprisingly, we did find that the macrophages did have a functional autophagy flux, even at the later stages of atherosclerosis, which was kind of interesting in itself. But when we looked at the vascular smooth muscle cell foam cells, though, that was a whole other story, and we found that these were actually defective at a very early stage and stayed defective up until the very late stage of atherosclerosis.   Cindy St. Hilaire:        And what is the very early stage like? What's that definition with the smooth muscle cell?   Sabrina Robichaud:    So we did a six-week time points in terms of our atherosclerosis study, and then a 25-week time point. So there are far apart, which shows like the very early, early stage and what would be considered the most effective autophagy at that point with the necrotic core and everything. So surprisingly, the two phenotype were quite similar at early and both late stages for both cell types, but were functional in the macrophages but dysfunctional in the smooth muscle cells.   Cindy St. Hilaire:        So you mentioned at one point in the discussion that you observed inconsistent lipid loading of the smooth muscle cells, and you mentioned that a lipase, which is excreted from the foam cells can then be internalized by, I assume kind of neighboring or in the vicinity, smooth muscle cells. And so the question I had it's kind of one of those chicken-and-egg question, and it's, is the smooth muscle cell-derived foam cell an independent process? Does it happen alone or de novo as a function of a smooth muscle-mediated process? Or is it really dependent first on this macrophage foam cell providing this lipid that is efflux that is then internalized by a smooth muscle cell that kind of goes on to become a foam cells. It's kind of a question of like the continuum of an atherosclerotic plaque and what do you think is happening, either based on your data or just kind of a hunch?   Mireille Ouimet:         That's an excellent question. And there's no doubt that macrophages really drive the initiating events of atherosclerosis. So I don't think that without the macrophage there would ever be a vascular smooth muscle cell, or there would be minimal vascular smooth muscle cell-derived foam cells. Definitely the inconsistencies that we observed in our study, were if we added like aggregated LDL on its own to a primary mouse vascular smooth muscle cell, we would get poor lipid loading and a very low percentage of those cells that would become foamy, relative to treating them with cyclodextrin complex cholesterol, for instance.   Mireille Ouimet:         So free cholesterol, that's cell permeable, will go into the vascular smooth muscle cell, no problem, and generate the foaminess and then allow that cell to acquire the macrophage-like phenotype. But aggregated LDL on its own in our hands, just gave very poor loading. And when we treated the vascular smooth muscle cells with aggregated LDL along with macrophage-derived condition media, we got some improvements, but it was still kind of inconsistent. But then we thought if we treat the vascular smooth muscle cells with aggregated LDL in the presence of conditioned media from macrophage foam cells that were preloaded with the aggregated LDL, would that promote their foaminess to a greater extent? And it did.   Mireille Ouimet:         So, there have been studies from Gordon Francis's lab that showed that adding recombinant lysosomal acid lipase to vascular smooth muscle cells that contained aggregated LDL, promoted the lysosomal hydrolysis of the aggregated LDL and to generate the foamy macrophages and allow the lysosomal processing. So we know that that vascular smooth muscle cells take up lysosomal acid lipase, and we know that macrophages undergo lysosome exocytosis and they can secrete lysosome acid lipase and acidify the extracellular milieu.   Mireille Ouimet:         So work from Fred Maxfield group has shown the presence of these cell surface connected compartments that are acidified, containing macrophage-derived lysosomal acid lipase, that even hydrolyze extra cellularly-aggregated LDL for macrophages. So we're not sure whether there's probably a local production of free cholesterol in the plaque by macrophages, this free cholesterol could be taken up by the vascular smooth muscle cell. And also the vascular smooth muscle cells do express some scavenger receptors, whether the expression of these scavenger receptors like LRP or CD36 even goes up when they've taken up a little bit of the free cholesterol. And then that allows the aggregated LDL to come in and then there would be some lysosomal acid lipase secreted by the macrophage foam cells that would promote the lysosomal processing of this aggregated LDL. All of those are very complex questions that will require some addressing in vivo models.     Cindy St. Hilaire:        You also mentioned in the paper that studies... There's a handful of them now. Studies have shown that between 30% and 70% of the cells that are staining positively for macrophage markers, meaning they're foam cells, are of the smooth muscle cell lineage. And so I believe people have seen that in mouse plaques with lineage tracing, but they've also used newer techniques to really see this also in human atherosclerotic plaques. So we know it's not just from a mouse, we know that smooth muscle cells can turn into a macrophage-like foam cell, and it's 30% to 70%, which is a huge range. Cindy St. Hilaire:        So do we know the factors that dictate whether a specific plaque is going to have more or less smooth muscle cell derived foam cells? And I guess more important to what you found in your paper is, how important would it be to know whether a plaque is on the 30% end or on the 70% end in terms of therapeutic strategies?   Sabrina Robichaud:    Yeah, most of these studies, the range can be attributed to the different time points at which these studies have been collected early on will be a little bit more macrophage understanding would be at a later time point. Now of course in terms of therapeutics, as we saw in our paper, metformin actually will positively increase cholesterol efflux in the vascular smooth muscle cell foam cells, but not in the macrophages. So obviously, being able to know at which point there's a majority of macrophages versus vascular smooth muscle cells, definitely going to determine which therapeutic we're going to be able to use.   Sabrina Robichaud:    Ideally, we would be able to find a therapeutic that would work in both foam cell, but from what we've seen, the mechanistic behind the autophagy dysfunction between both cell types are so different, that I'm not entirely sure that that would be possible, we would need some sort of combination therapy. But again, we need to be a little bit more targeted depending on the percentage of the foam cells that are comprising the plaque at that particular moment in time.   Cindy St. Hilaire:        Yeah, so you mentioned there's a function of time there. If you look earlier, there's more macrophage, if you look later, the percent of smooth muscle cell-derived foam cell increases. Is there a point in a very advanced atherosclerotic plaque where it's just mostly smooth muscle cells? Or do those macrophage foam cells stay, and it's just the increasing number of smooth muscle cell-derived foam cells? Do we know?   Mireille Ouimet:         This is an excellent question, and I was going to bring up the topic of clonal expansion of the vascular smooth muscle cells. So it's a very heterogeneous population and understanding that might be some of the differences that we see in different studies. It could be the model has one type of a smooth muscle cell that's expanding more than another, what are the factors that govern that? Does one clone take over at the later stages versus the earlier stages? We don't know.   Mireille Ouimet:         But we were surprised in our studies to see that the macrophages that are present at least on the lumen of the plaques were very active in autophagy. They had the highest staining for the phospho-ATG16L1 in that late stage. So we're not sure if it's newly-recruited macrophages that come in, that are more active and in autophagy, and then have good lysosomal capacity that keeps degrading the lipid present in the plaque and tries to ingest it, but also as a consequence keeps releasing some of the degraded cholesterol into the milieu where the smooth muscle cells that are proliferating are internalizing it and becoming more foamy. So these are really great open questions that need to be addressed in the field.   Cindy St. Hilaire:        So drug-eluting stents are coated with rapamycin or the various chemical compositions that are derived from rapamycin. And rapamycin itself induces autophagy. So while the thought behind using this coating on stents was to prevent smooth muscle cell proliferation, and thus restenosis or ingrowing of the stent, your study suggests that this could also help to promote autophagy in the cells underlying the stent. So has anyone gone in and looked at plaques that have been stented and either failed or not, and investigated the foam cell content or markers for autophagy activity?   Mireille Ouimet:         Not to my knowledge, and this has been something we've definitely... We think that this is what's happening. Some of the protective effects of these drug-eluting stents that have everolimus or sirolimus or the rapamycin or rapamycin analogs, we do believe that some of their protective effect can be attributed to autophagy activation, but this remains to be demonstrated. We think that autophagy activation locally would promote reverse cholesterol transport and would be one of the processes that prevents restenosis because we can promote the efflux of cholesterol out.   Cindy St. Hilaire:        Great. So I guess stemming from my question on the stents, what are the other translational implications of the findings of your study? And what would you like to see come out of this?   Mireille Ouimet:         So one of the things is, as Sabrina mentioned, would be to target both foam cell populations because it seems as though the vascular smooth muscle cell foam cells are very much defective in their autophagy capacity, and they're very poor effluxes, but we could potentially restore autophagy in the cell population to promote reverse cholesterol transport.   And looking at prevention of atherosclerosis is a bit different than looking at regression, because regression is at a later stage where the plaques are more advanced. And if they're mostly vascular smooth muscle cell-derived, maybe then those drugs that we're considering that protect against the development of atherosclerosis are effective on the macrophage themselves early on, but might not be mimicking what we would see in the clinic where the patients that present are older.   Cindy St. Hilaire:        Yeah, it's kind of really reminiscent of like the CANTOS trial and like, where do we want to target the therapy? It's going to be very different if it's an early smaller plaque, versus a late-stage possibly pro close to rupturing type of plaque. Well, Sabrina Robichaud and Dr Ouimet, thank you so much for joining me today. Congratulations again on a wonderful study, and I'm really looking forward to hearing more about this from your group.   Sabrina Robichaud:    Thank you.   Mireille Ouimet:         Thank you very much. And we also want to thank all the co-authors on the study, specifically also Adil Rasheed, who is co-first author on the work and Katey Rayner's group for all the support and involvement in this study.   Cindy St. Hilaire:        That's it for the highlights from the March issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @circres and #DiscoverCircRes. Thank you to our guests, Sabrina Robichaud and Dr Mireille Ouimet Sabrina. This podcast is produced by Ashara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles was provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire and this is Discover CircRes, you're on-the-go source for the most up-to-date and exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022, The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit ahajournals.org.

On this episode, Sujani sits down with Harman Sandhu and Aditi Garg from Public Health Connect (PHC). They discuss what PHC is and how it supports students and early-career professionals to succeed in the workforce. You'll LearnWhat Public Health Connect (PHC) is and what problem space it focuses onThe history of PHCWhat services are offered through PHC including networking eventsWhat the monthly opportunities round-up posted by PHC is How the team's own experiences inform the varied opportunities the round-ups  includeThe diversity of public health opportunities that are out thereThe current trends of public health jobsWhere else to find jobs for those looking to workWhat the hidden job market is and how to tap into itThe benefits of networking in seeking career opportunitiesToday's GuestHarman Sandhu is a public health policy and research professional who is currently completing a PhD at the University of Toronto. Prior to PhD studies, Harman worked in the Government of Ontario conducting race-based data analyses, disseminating research, and managing projects. He has published research on mental health stigma, smoke-free policies, and cannabis legalization. Harman co-founded Public Health Connect (or PHC) in 2020 as a volunteer-run community organization focused on supporting aspiring public health students and early-career professionals in Canada. He holds an MPH and BSc from McMaster University.Aditi Garg is a clinical research professional and health economics and epidemiology-based PhD trainee who currently oversees smoking cessation clinical trials in the Division of Cardiac Prevention and Rehabilitation at the University of Ottawa Heart Institute. Prior to her current role, Aditi worked in both academic and professional settings in both national and global landscapes with organizations such as Swiss Paraplegic Research Institute conducting population health data analyses and managing projects in areas of chronic disease prevention and management. She has published research on disability and rehabilitation policy, global health, and smoking cessation policies. Aditi also held an executive position as the Co-Director of Research and Marketing with Public Health Connect (or PHC) in 2021 as a volunteer-run community organization focused on supporting aspiring public health students and early-career professionals in Canada. She holds a masters degree in health economics and policy and BSc from the University of Waterloo.ResourcesDalla Lana's DrPH ProgramPublic Health Connect's Linktree including monthly opportunities round-upWebsiteInstagramFacebookLinkedInResearch article mentioned by HarmanSujani's previous interview with Heather KrasnaPH Spot's 6-week training programSupport the show (http://www.phspot.ca/signup)

Tune in for an in-depth discussion on the current and future state of coronary surgery. This series is led by Professor Pieter Kappetein, who is joined by Dr. Marc Ruel of the Ottawa Heart Institute, Dr. John Puskas from Mount Sinai Morningside in New York, and Dr. Teresa Kieser from the University of Calgary. Together, they will provide insights into the progress, current trends, and the future of coronary surgery — covering topics that include the role of total arterial revascularization, minimally invasive approaches, and learning outside of the fellowship.

Tune in for an in-depth discussion on the current and future state of coronary surgery. This series is led by Professor Pieter Kappetein, who is joined by Dr. Marc Ruel of the Ottawa Heart Institute, Dr. John Puskas from Mount Sinai Morningside in New York, and Dr. Teresa Kieser from the University of Calgary. Together, they will provide insights into the progress, current trends, and the future of coronary surgery — covering topics that include the role of total arterial revascularization, minimally invasive approaches, and learning outside of the fellowship.

Tune in for an in-depth discussion on the current and future state of coronary surgery. This series is led by Professor Pieter Kappetein, who is joined by Dr. Marc Ruel of the Ottawa Heart Institute, Dr. John Puskas from Mount Sinai Morningside in New York, and Dr. Teresa Kieser from the University of Calgary. Together, they will provide insights into the progress, current trends, and the future of coronary surgery — covering topics that include the role of total arterial revascularization, minimally invasive approaches, and learning outside of the fellowship.

This week's episode features highlights from Circulation's 2021 Cardiovascular Surgery Themed Issue. Join Executive Editor James de Lemos along with Associate Editors Marc Ruel and Michael Fischbein as they discuss all of the articles found in this special issue. Dr. James de Lemos: Hi, my name is James de Lemos. I'm a cardiologist at University of Texas Southwestern Medical Center in Dallas, and the executive editor for Circulation. And I'm standing in for Carolyn and Greg today to host our annual cardiovascular surgery-themed issue podcast. And I'm delighted to be joined by Marc Ruel, professor and chairman of the Division of Cardiothoracic Surgery at the Ottawa Heart Institute, and the director of cardiac surgery content for Circulation, as well as Michael Fischbein, associate professor of cardiothoracic surgery at Stanford and the director of the thoracic and aortic programs there. Marc, thanks for all that you do for Circulation with cardiovascular surgery content and let me turn it over to you to introduce the issue. Dr. Marc Ruel: Well, James, thank you very much. We're very delighted to introduce this 2021 cardiovascular surgery-themed issue. We already feel that this is going to put together some of the very best science at the interface between cardiac surgery or cardiovascular surgery, I should say, because there's some peripheral vascular topics as well, cardiology, and as well, mechanistic research. I think you're going to find that this is really a very jam-packed issue that has a lot of important messaging that will change the field going forward. Dr. Marc Ruel: Also, this year, I want to highlight a couple of changes in the preparation of the issue. I want to first thank the tremendous contributions over the years to Circulation and to the entire field of cardiac surgery of Tim Gardner. Really, Tim, is an absolute giant. I think he's the only person known to me who was both president of the American Heart Association and of the ATS in the field of cardiac surgery. Dr. Marc Ruel: Tim has really paved the way for us to develop and enhance this issue over the years, and I think 2021 is a testament to his legacy, because I would argue it's our strongest issue ever. And I also want to introduce Mike Fischbein, James and everybody, who's associate professor at Stanford. Mike is a thoracic-aortic surgery expert, also runs a translational lab, so has a very dedicated, basic science and translational surgical science expertise. So we're very, very happy to welcome Mike to the themed issue of Circulation. Dr. James de Lemos: Well, thanks Marc. We'll do is follow the order of the issue so that our readers and listeners can really get a sense of the content and its various types that we're publishing this year. And the issue starts with a provocative frame of reference piece from Verma and colleagues discussing the surgical left atrial appendage occlusion. Marc, what were your thoughts on that piece? Dr. Marc Ruel: It's obviously a game changer in cardiac surgery. I was privileged to serve as a part of the BSMB for this trial, and we can now say we toyed with the decision as to stop the trial at the appropriate time. And that's always a very difficult BSMB decision, which, frankly, you want to get it right, and you don't want to err on either side. Anyways, LAAOS III was recently published and we have a fantastic editorial in Circulation from Subodh Verma, Deepak Bhatt, and Elaine Tseng saying, which essentially highlights the importance of the trial for practice of cardiac surgery. Dr. Marc Ruel: It probably is that no patient who comes to cardiac surgery with a history of atrial fibrillation should, based on those findings, not have their atrial appendage ablated. There's already very little caveat, the trial has not shown what was feared prior with regards to an increased incidence of heart failure or symptoms. And really, the surgery has been effective. The ablation of the left atrial appendage is very effective in diminishing the primary outcome or of stroke, ischemic stroke or cerebral hemorrhage. Dr. Marc Ruel: And essentially, this was, in most cases, a surgical ablation, so cut and sew. So we don't have all the information about either endovascular devices or even ablative devices at the time of surgery. But it was a very large trial, it was a publicly funded trial. It is really the authoritative information in the field that's available so far. Dr. Marc Ruel: Mike, what are your thoughts around this? Do you now come to any one of your patients needing a cardiac surgical cooperation with a history of atrial fibrillation and thinking that I now need to address the left atrial appendage? Is that what you get out of this paper as well? Dr. Michael Fischbein: Yeah. Thanks, Marc. I think that's an excellent question. Yeah, now, every patient after this trial, I talk to them ahead of time and offer them to have their appendage ligated in this setting if they have a history of atrial fibrillation. I don't think this adds much to our operation, it doesn't increase much the clamp time. And especially, although the trial was more surgically excising with some of the newer clips out there, it really doesn't add much time to the operation. So I think this is really an important paper that will change what we do as surgeons. Dr. James de Lemos: Can I just comment that I think the trial has indirect implications well beyond surgery, because the demonstration of combined benefit for oral anticoagulation with left atrial appendage occlusion really suggests that, even for patients not going for cardiac surgery, at some point in the future, we may be thinking about not and either/or between the devices and anticoagulation, but maybe both. Dr. James de Lemos: Mike, let me come back to you. There's a really fascinating paper by DeCarlo evaluating penetrating aortic ulcers that really change my thinking on this. Can you talk a little bit about this paper and your thoughts? Dr. Michael Fischbein: Thanks very much, James. I think this is really an important paper that's going to change what we do as surgeons. As you know, symptomatic penetrating aortic ulcers are grouped with dissections in tremula hematoma where we treat those patients immediately. None of us know what to do though with the asymptomatic aortic ulcer, which is actually more common. A lot of us are basing our reports on some observational studies. Many of these studies are mixed, symptomatic and asymptomatic. And so the treatment really varies, from watching them conservatively to treating them with open or endovascular approaches. Dr. Michael Fischbein: However, this paper by DeCarlo's really excellent. They followed 273 asymptomatic penetrating ulcer patients over time following their CT scans. And they really had two key important findings. One that these ulcers really didn't change much over time, and two, the risk of some complication occurring, whether that's rupture, symptoms or progression of disease was very low at 6.5% over 10 years. And so I think this is really going to be important, because we know that these asymptomatic penetrating ulcers, we can watch them conservatively. They do have to be still followed, but we don't have to go immediately to perform some surgical procedure. Dr. James de Lemos: Marc, any thoughts from you on this paper? Does this change what you guys will be doing in Ottawa? Dr. Marc Ruel: Absolutely. Yeah, I think this is, as Mike was saying, a very germane finding that's very helpful. I think the key word here, as Mike was alluding to, is really the word asymptomatic and how do you define that? Right? I mean, many of these findings are incidental findings. Someone comes in with a bit of shortness of breath or this or that, gets a PE protocol CT scan and then a penetrating aortic ulcer is found. Dr. Marc Ruel: So where do you draw the line between symptoms that may be a small left lateral effusion or a bit of shortness of breath. And it's also, I think that nuance will have to be determined going forward, what is truly asymptomatic versus a few symptoms that may be less specific and perhaps not relate to the penetrating aortic ulcer. But I think it's tremendously helpful in guiding practice going forward. Dr. James de Lemos: Fantastic. Thank you both. Mike, I want to come back to you on another really important paper from the vascular surgery standpoint, which is the paper from the Voyager investigators on the combination of rivaroxaban and aspirin for patients with surgical treatment of peripheral arterial disease. Dr. Michael Fischbein: Yeah, no, I think this is another or provocative paper. And as you know, peripheral arterial disease is a really highly-significant clinical problem. We say that affects 200 million people globally. And this includes patients with claudication, arrest pain, limb threat ischemia. And currently, the treatment for this is to either a open surgical or endovascular revascularization of the lower extremity. And the problem is while these patients, they have immediate symptomatic relief where you can save their limb, we say that one out of five will develop some sort of symptom or limb ischemia by three years. Dr. Michael Fischbein: And so the field is really looking for some sort of adjuvant therapy to help prevent these occurrences later on. And so the Voyager trial randomized over 6,000 patients who underwent surgery, whether it was open or endovascular, and then they randomized to either receiving rivaroxaban plus aspirin, versus aspirin and a placebo. And they showed that if you received riva, that those patients had a significant reduction in the instance of their primary endpoint, which included ischemia, limb loss or symptoms. And importantly, there was not an increase in major bleeding risk in these individuals. Dr. James de Lemos: So fascinating. I mean, this does this change practice and is this now the standard for surgically-treated peripheral arterial disease? Dr. Michael Fischbein: Yeah, I think there's still some questions that we have to answer. Yeah, I think definitely this, I think will be used after the bypass surgery, but some of the things in the trial that we would have to figure out is how applicable is this to everyone. In the trial, the open surgical arm had patients with less risks. Also, some patients received vein conduit versus a prosthetic conduit. And so, I think we'll have to look at some of the sub-analysis to see who we can apply this to. Dr. James de Lemos: Fantastic. Marc, any thoughts from your perspective on this one? Dr. Marc Ruel: Yeah. Mike provided a great summary. I think one other take-home message to me is that, really, these patients should be viewed as having panvascular disease, a little bit like our CABG patients. And essentially rivaroxaban or DOACs in general have a role, like in the COMPASS trial, in preventing other complications. So here, part of the composite endpoint was myocardial infarction, right? And we know that these peripheral vascular disease patients are very much at risk of it. So it may have an effect locally, but it really, probably, has most of its effect with regards to the panvascular disease that these patients present. Dr. James de Lemos: Excellent. And I'll just point out that just today, the FDA released news that they've granted an indication for this combination therapy for patients with peripheral arterial disease. Let me come back to Marc for a really interesting randomized controlled trial, from China, evaluating no-touch vein graft interventions for cardiac surgery. Marc, can you talk to us about this trial and your impressions on this? Dr. Marc Ruel: Absolutely. Thank you, James. So this is a trial from seven hospitals in China that randomized 2,600 patients between April, 2017 and June, 2019. And patients were randomized with the use of saphenous vein grafts between a no-touch technique and a conventional saphenous vein graft harvest technique. And I'll explain a little bit what this no-touch technique is. It actually consists of two things. You take the vein by a complete incision. Often, in fact, it's more invasive, and you take the actual saphenous vein with a surrounding layer of fat and connective tissue around it. And because of that, it's not easily amenable to endoscopic vein harvest or even using small incisions. Dr. Marc Ruel: The other component of no touch of vein harvesting is to really preserve the anterior layer by not using any syringe inflation and letting the conduit be rinsed, but flow naturally and not be distended at all. So the trial was positive, and the trial already showed a lesser incidence of saphenous vein graft closure at both three months and 12 months on CT scan. So to give you an example, the three months saphenous vein closure was 4.8% in the conventional harvest group, versus 2.8% in the no-touch group. Dr. Marc Ruel: Now what's interesting to here is twofold. There may be a couple of aspects in the benefits of the therapy, and one may relate, in fact, to the lack of pressure syringe dilatation. So it's hard to tease out, is it really the surrounding layer of fat or is it the fact that the syringe dilatation procedure is not being performed in the no-touch group? The second issue is the technique is definitely more invasive. The authors found in the trial more local complications, about 50 to a hundred percent increase in terms of a local numbness, exudation, et cetera, delayed wound healing. Because you have to make bigger incisions and you have to take more tissue around where the vein that you're harvesting. Dr. Marc Ruel: So it is a very intriguing trial. Obviously, graph patency is something that's tremendously important around the CABG operation. But unfortunately, it steers us towards a more invasive approach. In a nutshell, it is a positive trial, but it does require the surgery to be slightly more invasive, albeit, in most cases, with addressable issues with regards to delayed wound healing and exudation. But it would be ideal if we could combine the benefits of a no-touch technique with a less invasive approach to harvesting. Dr. James de Lemos: Mike, this is fascinating to me because you've got a procedure that probably improves the long-term outcomes of the operation, but is associated with a longer surgical time and more local complications. Mike, I'm wondering, what are your surgeon's going to do at Stanford? Are they going to adopt this or is this too difficult and associated with too much inconvenience for the patient to become something that's done routinely? Dr. Michael Fischbein: Brilliant, great question, James. Because I think, often, our patients, previous to endoscopic vein harvesting, they often complained more issues with their leg incisions than their actual sternotomy. And I always tell my patients now, though, one of the incredible things is that we can take their vein endoscopically. And now, we're talking about, while we do have improvement in graft patency for the vein, we're going to go backwards and maybe have some of these wound issues again. And I'd be curious what Marc thinks, though. We are trying to do more and more arterial grafts. And so, if we're just using one vein, is it worth accepting these higher wound complications? Dr. Marc Ruel: It's a great point, Mike, and perhaps exactly, as you say, perhaps an increased use of arterial grafts can be combined with lack of a pressure syringe dilatation of the vein after harvest, right? And there's already some data suggesting, as provided in the excellent editorial by Vidal, that this may be mechanistically important to enhance patency. So the study is very intriguing and still remains to completely unfold. Dr. James de Lemos: Excellent. Really important contribution to the surgical science. Marc, I want to come back to you with another important randomized control trial, this with a really novel therapeutic compound designed to address kidney injury after cardiac surgery. Marc, can you talk about the trial with the small interfering mRNA for renal protection? Dr. Marc Ruel: Absolutely. Thank you, James. This is an important trial, in my opinion. It's a Phase II study of a compound named, teprasiran, which is a interfering RNA, which modifies the p53 mediated cell death response in the renal tubal cells. So what does that do, essentially, is that the thought is that it may prevent acute renal injury after cardiac surgery. We know that's a tremendous problem. Most busy cardiosurgical ICUs would have at least between 15 to 25% of the patients requiring dialysis postop, depending on the level of risk acuity that your unit is presenting. Dr. Marc Ruel: And it's no different whether you're in Stanford or Ottawa or Germany, in my opinion. So we need solutions here. And this is a relatively simple compound, which is administered within four hours of completion of surgery. So for instance, if the surgery was performed on pump, it was given within four hours of completion of surgery. So, for instance, if the surgery was on-pump, it was given within four of hours completion of CPB, cardiopulmonary bypass. If it had been performed off-pump, it was within four hours of the last anastomosis. Dr. Marc Ruel: It's a two-minute infusion, 10 milligrams per kilo, and essentially in the trial, it was not associated with any safety concerns. And quite conversely, it was actually associated with the benefit, with regards to the development of early acute kidney injury, which was 50% prevalence in the patients who were treated with placebo, versus 37% in patients who received the compound, again, named teprasiran. So I think this is quite important. It has led to a Phase III which is currently ongoing, and I think this is a very instrumental finding in the field. Dr. James de Lemos: Fantastic. I mean really a testament to the progress in clinical science for cardiac surgery, that we've got these randomized controlled trials moving through a development phase that may be actionable in years to come. Let's finish the discussion of the original research articles, Mike, with a review of the Yang paper, really, which also, I think, is in Circulation's real sweet spot, where we're highlighting the very best of basic and translational science coming from Surgeon Laboratories. Can you talk about that paper for us? Dr. Michael Fischbein: Thanks very much, James. I think this is really an exciting paper. Qiong Yang's lab at University of Michigan, they're studying Loeys-Dietz syndrome. As you know, Loeys-Dietz syndrome is one of the connective tissue disorders. There's five subtypes, and these individuals form aortic root aneurysms. Importantly, it's specific to the aortic root that these aneurysms primarily develop. Although later on, you can see them in other locations, including intracranial and some of the branch vessels. Dr. Michael Fischbein: But these root aneurysms can dissect and this is life threatening. Currently, the only treatment strategy for these individuals is surgical, where you perform a prophylactic replacement of the aortic root. Unfortunately, there are no real medical therapies, primarily because we don't understand the mechanisms why these aneurysms form. So Dr. Yang's lab, they model this disease using a induced pluripotent stem cell model, where cells are differentiated into the different embryologic origins of the aorta. Dr. Michael Fischbein: The aortic group comes primarily from the second heart field. And so, when they studied these smooth muscle cells, they were able to show that there is lineage-specific smooth muscle cell defects, and they discovered some interesting pathways that might explain why aneurysms form specifically in the root in these in individuals. They also came up with some potential pharmacologic strategies to block some of these mechanisms. Dr. Michael Fischbein: And so, I think this is really exciting because this is using pluripotent stem cells more as a model to study disease states. And I could see the potential, also, for precision medicine, where you take an individual cells, make their iPSCs and study that individual's mechanisms, and perhaps come up with unique medical strategies for that individual. Dr. James de Lemos: So let's, Marc, finish, that's really all of the original research articles we covered. Really, an amazing spectrum of clinical translational and basic science that is a Testament, both to what you all have done to recruit content, but the tremendous growth in science and the surgical specialties. Marc, let's talk a little bit about the two terrific in-depth reviews that you picked for this issue and what their contributions are. Dr. Marc Ruel: Thank you again, James. We have two excellent reviews in this themed issue of Circulation. One is a frontiers piece about cardiac surgery in women in the current era, going over what are the gaps in care. And this is spearheaded by Leslie Cho, from the Cleveland Clinic, and it really goes over, very comprehensively, many of the issues around not only clinical trial enrollment of women, but specific issues pertaining to the care, and which goes back even to basic science of the sex and gender of animals being used in research for reasons that I said, that are very comprehensively, again, I want to emphasize highlighted by the authors. Dr. Marc Ruel: And I'll give you an example, for instance. In off-pump surgery, there are some discrepancies with regards to the use of off-pump versus on-pump surgery between males and females. And we off-pump surgeons know that there are really two very different ways from the surgery. Women, for instance, have a smaller heart which is easier to expose, for instance, for lateral and inferior territories. But in the same token, the coronary targets can be smaller. So there's really a number of discrepancies here, which can be anatomic, it can be sometimes due to the disease presentations. Dr. Marc Ruel: For instance, women have more tricuspid valve disease, and at a certain age start having an increased incidence of aortic problems versus males. And there's also some what I would call logistical issues with regards, for instance, to clinical trial recruitments from VA centers that typically have very, very few women being eligible for enrollment there. So these issues, again, are comprehensively addressed by Dr. Cho and her colleagues. And it's a very interesting read. Dr. Marc Ruel: The other piece you were referring to is a state-of-the-art paper around the use of transit time flow measurements during coronary bypass. And I think our cardiology colleagues and everyone in the cardiovascular field will be very interested to learn a bit more about this. Because essentially, when we perform bypass surgery, we don't have a validated easy way to ascertain whether the grafts that we just built are doing their job. And you may say, "Well, the surgeon's great at cutting and doing anastomosis," but as I like to tell my trainees, there's much more than suturing that might be happening. Dr. Marc Ruel: An anastomosis may have an unforeseen flap into it. There could be a small clot that's blocking something. There could be a kink or a twist in the graft that's not readily recognized. So I think it's very important to have a thorough assessment in everybody. I'm the last author of this piece, so I'm obviously somewhat partial to it. But I think it is important for the field to have quality checking of all grafts that are performed at something, especially something as invasive as bypass surgery. The patient should come out with functional grafts and that should be validated and objectively verified. Dr. James de Lemos: Fantastic. Marc, and we also have two research letters in this issue of Circulation. These are small pieces, but they pack a really powerful punch. Do you want to just briefly tell us about those two? Dr. Marc Ruel: Absolutely. Thank you, James. As a surgeon, I love research letters. I think they are a great venue. They're under a thousand words. Certain, sometimes we're busy, we don't want to always read a 5,000-word manuscript. And they're really, they are well-suited to what I would say are surgical follow-up studies. Once a technique has been described and you want to look at what are the late outcomes of this technique, I think they're an excellent format for that. And precisely, this corresponds to the two research letters that we have in the 2021-themed issue. Dr. Marc Ruel: One is a long-term, 10 year analysis of the SAVE RITA trial by Kim and Kim in South Korea. The SAVE RITA trial is a fairly famous trial in our specialty, which essentially, randomized patients to have a Y graft on the left internal thoracic artery, using either a saphenous vein conduit or the right internal thoracic itself. And essentially the early results were neutral. So the two groups were comparable, which is naturally neutral. I would say non-inferior for the saphenous vein graft. Dr. Marc Ruel: Now we have 10-year data in over 200 patients, equally randomized between receiving a saphenous vein graft versus the right internal thoracic artery. And the results are 10 years are equally excellent between the saphenous vein graft and the right internal thoracic artery. So this is quite non-intuitive to many. Essentially, what we're showing here is that a vein graft at 10 years has amazing patency. We're talking 90%-plus in those patients who received an angiogram. So I think there's a couple of messages to remember here. Dr. Marc Ruel: There may be a biologic role of connecting a saphenous vein graft onto the left internal thoracic artery with regards to nitric oxide dilution. Also, technically, the authors have readily acknowledged that the harvest the vein, again, back to this saphenous vein harvest issue, they harvest it from the lower leg. Therefore, the diameter of the vein is more suited to a Y graft. And, in fact, using a vein over right internal thoracic artery may have technical advantages, because the diameter is a little bit more facile to use with regards to complex composite grafting. So it may actually be something that, if you can maintain it with patency based on say, nitric oxide dilution, is a little bit easier to maneuver and build at the time of surgery. Dr. James de Lemos: Marc, can I ask a question here? Does this change your practice with regard to how often you're using Y graphs, in general, and the vein on artery Y? Because, Mike, outsiders experiences that these graphs aren't used and do these data suggest that we should be using why Y graphs, in general, and this particular type of Y more often in surgery? Dr. Marc Ruel: Absolutely. I think these data suggest precisely that. Whether the adoption will follow is another story. There's not a lot of groups, much to your point, that are using this configuration, but it's used commonly as a bailout strategy. Let's say, one of the arteries has been injured or is not available, or you have a porcelain aorta, I think based on these important data, you can now know that you can, if well-constructed, use a saphenous vein graft as a Y graft onto the LITA with relative impunity. In fact, excellent results, if done in the way that Kim and Kim are reporting. Dr. Marc Ruel: Our second research letter is actually a follow-up of hybrid palliation for hypoplastic left heart syndrome. This comes from the UK, where a number of centers had used several years ago the concept of a hybrid palliation in patients who were mostly high risk for hypoplastic left heart. So here, again, much to the research letter format, we have a follow-up series with regards to following all these children who had received either a initial Norwood approach or a hybrid approach progressing to a Norwood stage two. And essentially, the overall survival, which is about, between two thirds to 75% of children at three, four years, is no different between an initial Norwood stage one approach versus hybrid palliation. Dr. Marc Ruel: So I think this is obviously very intriguing data. It's used to be that a hybrid palliation would only be used in very high-risk cases. I think this would provide credence to using it in a more liberal fashion. There's still the possible caveat that the centers that use hybrid palliation have a little bit of a "expertise bias," if you will, because they have both modalities being available. But I think this is a very important and very intriguing data for this extremely challenging condition. Dr. James de Lemos: Well, thank you. And I'd like to thank both you, Marc, and Mike for just tremendous insight. I think for somebody that doesn't live in the cardiac surgery world, having the privilege, not just to hear you explain these terrific studies, but also provide your insights in pearls about cardiac surgery and vascular surgery care in 2021 has been invaluable. And I think our listeners will feel the same way. I'd like to turn it over to you, Marc, as our leader in cardiovascular surgery to close us out today from a wonderful podcast. Dr. Marc Ruel: Well, thank you very much, James. Again, I want to reiterate, I think this is really a tremendous issue. It's our best ever. And I want to thank you, James and Joe Hill, as well, our Editor-in-Chief, for your support of surgery within Circulation. I also want to thank Sarah, Molly, Nick, and Augie, really, for their in their indefatigable support of our issue. I want to, again, extend our gratitude to Tim Gardner and to Mike for their tremendous help with this issue. I think this is, again, very important. Do send your best work, and I'm speaking to our readership community and all surgeons to Circulation. Dr. Marc Ruel: Circulation is our premier journal and surgery's tremendously important. And the interface together is a strong one, because Circulation realizes that surgery provides, and I'm a bit biased when I say this, but I think it is true. It provides the most robust and durable treatment for advanced heart disease, so it is very important to be featured prominently in Circulation. And I think this is what our current leadership and staff at Circulation are supporting, and I'm tremendously thankful on behalf of all surgeons. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.

What does the body of evidence have to say on the topic of blood pressure? Plus: what seems to be causing multiple chemical sensitivity, and we come face to face with the difficulty of deciding if an activity is risky or not when you're fully vaccinated.   Block 1: Blood pressure: what the numbers mean (2:27)   Block 2: Blood pressure: should you treat it, what to aim for, how to treat it, how best to measure it (8:56)   Block 3: Multiple chemical sensitivity, what happens when tests come back negative, and the ethics of prescribing placebos (28:11)   Block 4: Question about the HPV vaccine and the immune system (45:56) Wrong numbers in Ottawa Heart Institute study scare people (48:12) Is this risky? (53:16)     * Jingle by Jillian Correia of Roctavio Canada * Theme music: “Fall of the Ocean Queen“ by Joseph Hackl. * Assistant researcher: Nicholas Koziris   To contribute to The Body of Evidence, go to our Patreon page at: http://www.patreon.com/thebodyofevidence/.   To make a one-time donation to our show, you can use PayPal! https://www.paypal.com/donate?hosted_button_id=9QZET78JZWCZE   Patrons get a bonus show on Patreon called “Digressions”! Check it out!     References:   1) John Hay quote: https://pubmed.ncbi.nlm.nih.gov/20776269/   2) Oslo study: https://pubmed.ncbi.nlm.nih.gov/7001898/   3) MRC study: https://pubmed.ncbi.nlm.nih.gov/2861880/   4) SPRINT study: https://www.nejm.org/doi/full/10.1056/NEJMoa1511939   5) ACCORD study: https://www.nejm.org/doi/full/10.1056/NEJMoa1001286   6) STEP trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2111437   7) SSaSS study on salt substitute: https://www.nejm.org/doi/10.1056/NEJMoa2105675   8) ALLHAT trial: https://jamanetwork.com/journals/jama/fullarticle/195626   9) ACC/AHA systematic review: https://pubmed.ncbi.nlm.nih.gov/29133355/   10) Jonathan's article on the INSPQ report on multiple chemical sensitivity: https://www.mcgill.ca/oss/article/health/zeroing-cause-multiple-chemical-sensitivity   11) The INSPQ report on MCS (French only): https://www.inspq.qc.ca/publications/2729     Music:   Fanfare for Space by Kevin MacLeod Link: https://filmmusic.io/song/3736-fanfare-for-space License: https://filmmusic.io/standard-license   Guitar Hero by Alexander Nakarada Link: https://filmmusic.io/song/4807-guitar-hero License: https://filmmusic.io/standard-license   Good Ideas For A New Startup by MusicLFiles Link: https://filmmusic.io/song/8159-good-ideas-for-a-new-startup License: https://filmmusic.io/standard-license

Sol Vidal from the University of Ottawa Heart Institute talks to Leonard Benoit from the Toronto Central Regional Cancer Program. Join us in this Beats Research Radio episode as we speak with Leonard Benoit, the Indigenous Patient Navigator for the Toronto Central Regional Cancer Program, about the importance of his role to make our healthcare system more culturally safe and accessible for indigenous people in Canada.Learn more: www.Trcp.ca

Isabela R Marçal from the Sao Paulo State University (UNESP) talks to Dr. Thais Couthino from the University of Ottawa Heart Institute about women and arterial health: current and future perspectives. Learn more about why we need to do more for Women’s Cardiovascular health with this special episode as part of the 2021 series of Women in Science.  Learn more about Dr. Couthino’s research: https://cwhhc.ottawaheart.ca/

Sol Vidal from the University of Ottawa Heart Institute talks to Dr. Fernanda Duarte from Oxford University about how she incorporates equity, diversity and inclusion strategies in her research lab and the benefits that EDI brings personally and professionally. Learn more about EDI in Chemistry with this special episode as part of the 2021 series of Women in Science.Learn more about Dr Duarte's research http://fduartegroup.org/ 

Jessica Luc of the University of British Columbia in Canada interviews Marc Ruel of the University of Ottawa Heart Institute about his pioneering work in minimally invasive cardiac surgical operations. They discuss his career, the importance of mentorship, and the development of current minimally invasive cardiac techniques.

Lara Gharibeh from the University of Ottawa Heart Institute talks to Dr. Hanan Anis, Professor and Faculty Coordinator in Entrepreneurship and Innovation at the University of Ottawa, Faculty of Engineering. Dr. Anis shares with us her career journey from industry to academia highlighting her challenges and the lessons learned. She also expands on the new master program for engineering and entrepreneurship recently developed at the University of Ottawa and gives advice for the next generation. Learn more about Dr Anis research: https://engineering.uottawa.ca/people/anis-hanan

Sol Vidal from the University of Ottawa Heart Institute talks to Dr. Juan Grau, Director of Cardiothoracic Surgery at Valley Health System. Dr. Grau shares with us lessons learned during his remarkable career as a surgeon and researcher in several world-renowned universities and reminds us of the importance of addressing gender bias. Learn more about Valley Health Systems: www.valleyhealth.com

Janïs Petit from the University of Ottawa talks to Dan Pak who is a passionate runner, heart health advocate, and an Atrial Fibrillation patient at the University of Ottawa Heart Institute. Dan with us lessons on how important is for everyone to be conscious that Heart diseases can affect even those physically active and how research at the Heart Institute has benefited his recovery.Learn more about Dan’s inspiring journey www.ottpak.blogspot.com and follow Dan on Twitter @OttPak

February is Heart Month. For people living with diabetes, heart disease is one of the most common complications. Dr. Erin Mulvihill is a scientist from the Ottawa Heart Institute whose research tries to better understand this connection in order to improve treatments.

February is Heart Month. For people living with diabetes, heart disease is one of the most common complications. Dr. Erin Mulvihill is a scientist from the Ottawa Heart Institute whose research tries

Episode 58 BEaTS Research Radio – Interview with Dr. Harriette Van Spall. Sol Vidal Almela from the University of Ottawa Heart Institute talks to Dr. Harriette Van Spall from McMaster University. A conversation on the importance to avoid sex-related exclusion criteria (pregnant, lactating) if not based on evidence, educating patients about research participation benefits, and have a diverse group of leaders, we need more women in cardiology!Learn more about Dr. Harriette Van Spall https://experts.mcmaster.ca/display/vanspahRegister for participating in the 2021 Canadian Women's Heart Health Summit (February 10-13th 2021): http://cwhhc.ottawaheart.ca/summit

Episode 55 BEaTS Research Radio – Interview with Lisa Comber. Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Lisa Comber, Knowledge Translation Lead, at the Canadian Women's Heart Health Centre. A conversation on what to expect of the 2021 Canadian Women's Heart Health Summit. Learn more about the 2021 Canadian Women's Heart Health Summit: http://cwhhc.ottawaheart.ca/summit

Episode 53 BEaTS Research Radio – Interview with Dr. Peter Liu. Nicole Chun from the University of Ottawa talks to Dr. Peter Liu, Chief Scientific Officer at the University of Ottawa Heart Institute. A conversation on the impact of COVID-19 on cardiovascular health and vaccines. Learn more about the University of Ottawa Heart Institute: www.ottawaheart.ca

Episode 52 BEaTS Research Radio – Interview with Dr. Thierry Mesana. Janïs Petit from the University of Ottawa talks to Dr. Thierry Mesana, President and CEO, University of Ottawa Heart Institute. A conversation on the impact of COVID-19 on the cardiovascular health of Canadians. Learn more about the University of Ottawa Heart Institute: www.ottawaheart.ca

Episode 51 BEaTS Research Radio - Interview with Dr. James Woodgett. Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. James Woodgett, Director of Research at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System. A conversation about James Woodgett’s view on the Science and Policy path and the importance of communicating Science to our communities. Learn more about the Lunenfeld-Tanenbaum Research Institute: www.lunenfeld.ca

This week's episode features authors David Kasss and Kavita Sharma as they join Greg to discuss their article "Myocardial Gene Expression Signatures in Human Heart Failure with Preserved Ejection Fraction." TRANSCRIPT BELOW: Dr. Carolyn Lam: Welcome to Circulation on the Run. Your weekly podcast, summary, and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: I am so excited about today's feature paper. It talks about my favorite topic, heart failure with preserved ejection fraction, or HFpEF, this time giving us really novel myocardial gene expression signatures in human HFpEF. Can't wait to go to that, but I also can't wait to share about some of the really cool papers in today's issue. Dr. Carolyn Lam: Now, we know that mitral valve-in-valve and valve-in-ring are alternatives to surgical reoperation in patients with recurrent mitral valve failure after a previous surgical valve repair or replacement. But, what are the outcomes after transcatheter mitral valve-in-valve or valve-in-ring procedures? And what is the clinical significance of post-procedure residual mitral stenosis or regurgitation? Well, we're going to find out in today's paper. Dr. Dvir from Hebrew University in Israel and authors examine the midterm outcomes in the Valve-in-Valve International Data registry, which is a multicenter collaboration and rolling cases performed between March, 2006 and 2020, in 90 centers worldwide. Dr. Greg Hundley: Wow, Carolyn. So what did they find? Dr. Carolyn Lam: Well, a total of 1079 patients were included with a median follow-up of 492 days. 4-year Kaplan-Meier survival rate was 62.5% in the valve-in-valve, versus 49.5% in valve-in-ring procedures. Significant residual mitral stenosis occurred in 8.2% of the valve-in-valve, and 12% of the valve-in-ring patients. Significant residual mitral regurgitation was more common in valve-in-ring patients. The correlates for residue mitral stenosis were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual mitral regurgitation was a valve-in-ring procedure. Significant residual mitral stenosis and residual mitral regurgitation were both independently associated with repeat mitral valve replacement. Dr. Carolyn Lam: So, significant residual mitral stenosis and/or mitral regurgitation were not infrequent after mitral valve-in-valve and valve-in-ring procedures, and we're both associated a need for repeat valve replacement, so strategies to improve post-procedural hemodynamics in mitral valve-in-valve and valve-in-ring should certainly be further explored. Dr. Greg Hundley: Very nice, Carolyn. Well, my first paper, it really involves results from the American Heart Association COVID-19 Cardiovascular Disease registry, and it comes from our own associate editor, Dr. Justin Grodin from UT Southwestern Medical Center. So Carolyn, obesity may contribute to adverse outcomes in coronavirus disease, or COVID-19. However, studies of large, broadly-generalizable patient populations are still lacking in the effect of body mass index, or BMI, on COVID-19 outcomes, particularly in younger, adults remains uncertain. Dr. Carolyn Lam: Yeah. It is an important question. And so, what did they find? Dr. Greg Hundley: Well, Carolyn, obese patients are more likely to be hospitalized with COVID-19, and are at higher risk of in-hospital death or mechanical ventilation, in particular, if they're young. So individuals less than age 50 years. Obese patients are also at higher risk for venous thromboembolism and dialysis. These observations support clear public health messaging and rigorous adherence to COVID-19 prevention strategies in all obese individuals, regardless of age. Dr. Carolyn Lam: Wow. An important public health message. Well, my next paper is a basic science one from doctors, Rayner and Karunakaran from University of Ottawa Heart Institute in Canada. For the first time, they investigated the role of RIP kinase 1, a coordinator of NF-kappa B inflammation and cell death, in atherosclerosis. Dr. Carolyn Lam: They found that RIP kinase 1 expression was highly expressed in early atherosclerotic lesions in humans and mice. In vitro, both basal and TNF alpha stimulated NF-kappa B activity, and resultant inflammatory gene expression was reduced in macrophages and endothelial cells when RIP kinase 1 was silenced. In vivo therapeutic administration of RIP kinase 1 antisense oligonucleotide markedly reduced atherosclerotic lesion size and macrophage content. Dr. Carolyn Lam: Together, these findings suggest that RIP kinase 1 drives inflammation in early atherosclerosis, and targeting RIP kinase 1 therefore provides a novel preventive strategy to treat atherosclerosis. Dr. Greg Hundley: Very nice, Carolyn. Well, my next paper comes from Dr. Kristin Stanford from The Ohio State University. So, Carolyn, brown adipose tissue is an important tissue for thermogenesis, making it a potential target to decrease the risk of obesity, type 2 diabetes, and cardiovascular disease, and recent studies have also identified brown adipose tissue as an endocrine organ. Dr. Greg Hundley: While brown adipose tissue has been implicated to be protective in cardiovascular disease to this point, there are no studies that identify a direct role for brown adipose tissue to mediate cardiac function. This study was performed to address this issue. Dr. Carolyn Lam: So what did they find? Dr. Greg Hundley: Okay, Carolyn. The authors found that transplantation of brown adipose tissue improves cardiac function via the release of the lipokine 12,13di-HOME. Sustained overexpression of 12,13di-HOME using tissue nanotransfection negated the delirious effects of a high-fat diet on cardiac function and remodeling, and acute injection of 12,13di-HOME increased cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13di-HOME increase mitochondrial respiration. So, Carolyn, these results identify an endocrine effect of brown fat to enhance cardiac function. Dr. Carolyn Lam: So interesting. Well, there are other very interesting types of papers in today's issue. There's an exchange of letters between Drs. Gui and Nahrendorf regarding the article Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes. Dr. Carolyn Lam: In cardiology news, Tracy Hampton highlights articles from Nature Biomedical Engineering on AI-based eye movements for cardiovascular risk prediction, from Science on the metabolic profiling of the failing and non-failing heart, and from Science Translational Medicine on the heart healing effects of extracellular vesicles. Dr. Carolyn Lam: There's an On My Mind paper by Dr. Pelliccia on gaps in evidence for risk stratification for sudden cardiac death in hypertrophic cardiomyopathy, as well as a Research Letter by Dr. Brown on the association of inducible myocardial ischemia with long-term mortality and benefit from coronary artery bypass graft surgery in ischemic cardiomyopathy, which is a 10-year follow-up of the STICH trial. Dr. Greg Hundley: Nice, Carolyn. Well, my articles: Professor Himbert has an In-Depth article on the current indications for transcatheter mitral valve replacement using transcatheter aortic valves, valve-in-valve, valve-in-ring, and valve in mitral annulus calcification. There's a Research Letter from Dr. Martin (Than) regarding the single troponin rule-out of myocardial infarction. And finally, Professor Isser has an ECG challenge involving chest pain with ST-segment elevation in a young woman with a broken heart. Dr. Greg Hundley: Well, now how about we proceed to that feature discussion? Dr. Carolyn Lam: Yay. Let's go, Greg. Dr. Greg Hundley: Well, listeners, we want to bring you to our feature discussion today, and we have with us Dr. David Kass and Dr. Kavita Sharma both from Johns Hopkins University in Baltimore, Maryland. David, could you tell us a little bit about the background related to this study and what hypothesis did you want to test? Dr. David Kass: Sure, Greg. My pleasure to be here. We have long had an interest in the syndrome we know as heart failure with preserved ejection fraction, going back, really, decades, and the difficulty in assessing what's really wrong with the heart in this syndrome has been that we get so little information from the tissue itself, that most of the studies that have been done have been done at the macro level and physiology level and epidemiology level. Dr. David Kass: But at Johns Hopkins, Kavita Sharma, who now heads up our heart failure transplant group, had established a clinic, a HFpEF clinic, one of the very few in the United States, and the availability of both the patients through the clinic, and then as part of this, right heart catheterizations associated with endomyocardial biopsies being obtained, was really a very extraordinary opportunity to examine tissue at a molecular level, essentially for the first time. There's been no other data set quite like this one. Dr. David Kass: So, we had already established both a patient population, very, very well-phenotyped, very much symptomatic, and we had a tissue bank. And as part of a consortium, a network consortium grant that was sponsored by the American Heart Association, called the Go Red for Women Network, we had a project that basically was focused on trying to better understand HFpEF. Dr. David Kass: The impetus was really, no one knew anything about what's going on in the heart at the molecular level. Really. There had not been transcriptomic analysis ever done before, and there were plenty of questions that we thought this might be able to answer. Among them, how really different are these hearts from patients who have, what we'll call, garden-variety heart failure, heart failure with a low ejection fraction? That's seemingly not so controversial now, but actually there's still controversy as to exactly what's wrong with these hearts, and so we thought we would be able to tease that out. Dr. David Kass: Then it's also been, I think, widely discussed that this is a very heterogeneous disease or syndrome, really, that has a lot of different factors, comorbidities, that are associated with it. So question two was really, how cohesive is the molecular signature that you might see in the myocardium? Is it going to be hopelessly heterogeneous as well, in which case, what does that say about our possibility to develop drug therapies when the underlying biology may be very, very heterogeneous? And if not so heterogeneous, question followup would be, what signatures might be there in subgroups that we could identify, and with subgroup analysis then, help us target in a more personal medicine fashion, ultimately, a therapeutic for the syndrome? Dr. Greg Hundley: Very nice. So, David, how did you assemble a study population, and what was your study design? Dr. David Kass: In this sense, this was very much an ongoing effort by Dr. Sharma and what was the HFpEF clinic team. Back, probably about 4 years ago, maybe even more, she had started to become interested in this and had amassed a clinic population while she was a resident, and then as a senior resident became more and more interested in this and this became her fellowship project when she was a cardiology fellow at Hopkins. Dr. David Kass: And by the time I became more involved with this, basically she had it in operation with study nurses and seeing patients. It was very clinically-oriented. There was some sort of more, I would say, population-level data being collected and studies being done, but nothing like quite what we did here. But that was there. Dr. David Kass: So, in terms of a study design, this was almost more a biobank. At this point, there was a cadre of patients she had been following. She had been following this group for some time. Basically, in a freezer we had endomyocardial biopsies under an IRB-approved protocol that had been obtained, and in part we were sort of waiting to get enough tissue together so we had a large enough data population and enough sample, and then really thinking through what might we be able to look at in these pieces, knowing full well that very little had been done. So almost anything we came up with, and we've been doing quite a few other things now as well, was going to be new, so I suppose the simplest study design of all. Dr. Greg Hundley: So, what did you find? Dr. David Kass: Well, going through those initial questions. Question number one, is there a unique molecular signature? We're looking at using what's called RNA-Seq, which is the newest generation of RNA gene expression analysis, in these myocardial biopsies. The answer was, yes, actually. There was a very unique signature. And this was all done using what we call agnostic bioinformatics approaches, where you just give the data, you give all the genes that are different between HFpEF and a control group, we had a control group, donor hearts. You look at basically the HFrEF group, the people with low ejection fraction, versus control. What are those differentially expressed genes? And of course you have your control. Dr. David Kass: So there are three groups and you get a series of little dots in what's called principal component analysis, and it was very clear, right from the beginning, that these groups separated, and this was just purely a statistical approach to say, are they different? Dr. David Kass: And then we asked further, are they still different even if we adjust for what are the common comorbidities and the things that differentiated, often, HFpEF from other forms of heart failure, specifically age, sex, having a large body mass index, having diabetes, these were all things that were more prevalent and more severe in the HFpEF group. So we adjusted for these things, again, sort of statistically, and redid this, and it's still absolutely separated. So question one, are they different at the transcript level? Yep. They're different. Dr. David Kass: And then, question two is basically, despite the heterogeneity, if you start digging into the genes, what kinds of genes are being differentially regulated? Is there a signature that becomes cohesive and consistent among the patients within the HFpEF group? The answer to that was, yes. And this too was very interesting because we also did an adjustment for the comorbidities, and what we found were the genes that were upregulated in HFpEF, that actually turned out mostly to be down-regulated in the other form of heart failure. Genes specifically associated with the manufacturing of ATP by mitochondria, the ATP synthase genes, those genes were significantly upregulated in HFpEF, but once you adjusted for body mass index, a lot of those pathways disappeared. So, the class of genes that were up regulated was in fact related to comorbidities. Dr. David Kass: Then we did the opposite. We looked at those genes that are down-regulated, and found that a large group of genes that were quite different, that are not on the tip of most people's tongues for what goes on in heart failure, mostly associated with protein processing, trafficking, autophagy, the process of protein recycling, endoplasmic reticular stress, which was something that the journal senior editor, Joe Hill, had talked about and published about earlier in the year in a mouse paper where he first came up with this idea that ER stress might be important. Well, looks like it's important in these humans. So, we found some unique signatures. Dr. David Kass: And then the last thing I suggested we would look at is whether we could get subsets from the molecular signatures, and the answer to that was, yes. Here we kind of threw the genes at a program and said, "You come up with clusters, purely based on the genes." That's it. No clinical information whatsoever. What it came out with were three groups, and very interestingly, there was a mortality difference between these groups just based on their transcript. One of the groups looked at pretty close, or closer, to HFpEF to reduced EF heart failure, and indeed, the genes that it came up with were typical of hypertrophy and remodeling and matrix remodeling, and that was the one with a group with the highest mortality. And then there was sort of a very different group with small hearts, relatively low levels of natriuretic peptide, an inflammatory pathway signature. Not the kind of thing we're to looking at and say, "Oh yeah, this is obviously heart failure," and yet they were equally symptomatic, tended to be a few more on the female side than male side. Dr. David Kass: So, I think, in the end, that study was very successful for all the things we were trying to do, really. That it's distinctive, that there are subgroups that we can identify at the transcriptome level, despite the heterogeneity, and we've got a list of genes now, pathways, really, that look to to be uniquely relevant. Dr. Greg Hundley: Very nice summary. Well, let's turn to your colleague, Dr. Kavita Sharma, who is also with us today and helped assemble this wonderful cohort. Kavita, how would you put these findings in the context with some of the other literature that's been published in heart failure preserved ejection fraction? Dr. Kavita Sharma: Hi, good morning. Thanks for the opportunity. That's a great question. The idea of trying to phenotype HFpEF has really been around, for now, a couple years, and that's driven by the fact that we have no therapeutic agents to date that have really affected outcomes in this population, in spite of the fact that half of all heart failure is classified as HFpEF and we have many therapies for HFrEF, or low ejection fraction patients. Dr. Kavita Sharma: And the thought is that, perhaps, it's a heterogeneous population and we're lumping to many different types of patients together. And so there have been a number of efforts to date to try to phenotype this population, but most of these have been centered around clinical comorbidities, and distinct groups have been identified, but without a clear sense of what is driving mechanistic differences between the groups, and then how to take it to the next step to target therapeutic agents to specific populations within HFpEF. Dr. Kavita Sharma: I think this is a big step closer to trying to really understand how we can target therapies. So, we've seen efforts at phenotyping and there are some overlap between the three groups that we identified from our RNA sequencing work, but this is now giving us a clue as to how to target mechanisms of disease. Dr. Greg Hundley: Very nice. Well, Kavita what do you see is the next study to perform, really, in this space, to follow your work? Dr. Kavita Sharma: Our goal is to really perform a comprehensive, as we call it, omics approach to phenotyping and HFpEF. We are actively looking at metabolomics, both from the blood and the tissue in collaboration with investigators at U Penn, we hope to also look at proteomics, and eventually single cell sequencing, as well as really trying to understand some of the actual myocyte-level contractility issues. And this is work that actually has just come out as well from our group, looking at sarcomere function in HFpEF from the right ventricle. Our hope is that each of these areas is going to further our understanding of myocardial deficits, so to speak, and areas that we could target for therapies. Dr. Greg Hundley: Very nice. David, do you have anything to add to that? Dr. David Kass: No. I think Kavita said it very, very well, and clearly the goal is to ultimately develop a more mechanistically-driven, personalized approach to the subsets of HFpEF so that hopefully we get a therapy that actually is going to work. These are not tiny subsets of this group. Remember this is half of all heart failure and that's a big number, and even a subgroup that might represent one-quarter of half of all heart failure is still a big number, and so none of this is ever going to be like an orphan disease suddenly where we're dealing with a very small group of people. Dr. David Kass: But even if it was, it would still be a major step forward, but it's not going to be that. I think what you're going to hopefully come up with, with a signature that can be targeted and with the therapy that's effective on the basis of that, is going to, I think, help a large population. Dr. Greg Hundley: Well, listeners, we want to thank Dr. David Kass and Dr. Kavita Sharma, both from Johns Hopkins University in Baltimore, Maryland for bringing us this new information related to RNA sequencing to really help better phenotype patients with heart failure and preserved ejection fraction, so that in the future, we may have therapies that can help this patient population. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021.  

Episode 50 BEaTS Research Radio - Interview with Dr. Michael J. Strong. Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Michael J. Strong, president of the Canadian Institutes of Health Research (CIHR). A conversation about Dr. Strong’s academic path from student to senior scientist, the current and future goals of CIHR, and important advice for early-career scientists.Learn more about the Canadian Institutes of Health Research: https://cihr-irsc.gc.ca

Dr. Carolyn Lam : Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley : And I'm Greg Hundley, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam : Greg, today's feature paper is a research letter, but, oh my gosh, it is so interesting. It's about surgical explantation of transcatheter aortic bioprosthesis. TAVRs we know is on the rise and so is the rise of surgical explantation cases and we really need to understand it better. Hang on, we're coming to that, but maybe, let's start with some other papers in the issue first, shall we? Let me go first, you go grab your coffee and listen because we're going to talk about the efficacy of ertugliflozin on heart failure related events in patients with type II diabetes and established atherosclerotic cardiovascular disease in the results of the VERTIS CV trial. Dr. Greg Hundley : Carolyn, tell us a little bit about the VERTIS CV trial. Dr. Carolyn Lam : Sure. The primary results of the VERTIS CV trial have already been published. This cardiovascular safety trial was actually performed to satisfy the 2008 guidance from regulatory agencies for new antihyperglycemic agents. It found that patients with type II diabetes and atherosclerotic cardiovascular disease randomized to ertugliflozin achieved the primary objective of non-inferiority to placebo in time to first major adverse cardiovascular event or MACE, a composite endpoint of cardiovascular death, non-fatal MI, or non-fatal stroke. The first secondary outcome in the hierarchal testing sequence was superiority for the time to composite of cardiovascular death or heart failure hospitalization, which was not met and therefore formal hypothesis testing ended with this endpoint. Now in today's paper, the authors led by Dr. Cosentino from Karolinska Institute and Karolinska University Hospital in Stockholm, Sweden, present the results from pre-specified analyses of the effect of ertugliflozin versus placebo on a series of heart failure related outcomes from this VERTIS CV trial. Dr. Greg Hundley : Ah, Carolyn. Tell us what were the results of this new study. Dr. Carolyn Lam : Of more than 8,200 randomized patients, almost 24% had a history of heart failure and almost 61% had a pre-trial ejection fraction available, including 959 patients with an injection fraction less than or equal to 45%. While ertugliflozin did not significantly reduce first heart failure hospitalization or cardiovascular death, it did reduce first and total hospitalization for heart failure events with a relative risk for first heart failure events being similarly beneficial number one, in those with versus without a history of heart failure and number two, in those with a history of heart failure with reduced ejection fraction or preserved ejection fraction. However, the risk reduction tended to be greater for those with an ejection fraction less than or equal to 45%. Although, the test for interaction by injection fraction was not significant. The effect of ertugliflozin on risk for first heart failure hospitalization was consistent across most baseline subgroups with a greater effect in three populations, including those with impaired kidney function and those taking diuretics. Now, this is discussed an editorial by Doctors Faiez Zannad and Martin Cowie. You must pick it up and read it. Dr. Greg Hundley : That's great, Carolyn. What a fantastic another piece of information on the SGLT2 inhibitors. Dr. Greg Hundley : Well, my first paper comes to us from Dr. Peter Liu from the University of Ottawa Heart Institute and his colleagues. Carolyn, this article focuses on cardiac hypertrophy, which as you know, is a key biological response to injurious stresses such as pressure overload. Also as you know, when cardiac hypertrophy is excessive, it can lead to heart failure. Innate immune activation by danger signals through intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain-containing protein 1, or NOD1 and its adaptor receptor interacting protein, RIP2, may play a major role in cardiac remodeling and progression to heart failure. These authors hypothesized that NOD1 and RIP2 are major contributors to cardiac hypertrophy, but may not be sufficient to fully express the phenotype alone. Dr. Carolyn Lam : I like that, NOD1 and RIP2. What did they find? Dr. Greg Hundley : These authors found that innate immune NOD1/RIP2 signaling was a major contributor to cardiac remodeling following stress. This process was critically joined by and regulated through the mitochondrial danger signal protein adapter MAVS. The authors found that this novel complex coordinates remodeling, inflammatory response and mitochondrial energy metabolism in stressed cardiomyocytes, thus NOD1/RIP2 MAVS signaling complex may represent an attractive new therapeutic approach toward modulating LV hypertrophy mediated heart failure. Dr. Carolyn Lam : Very nice, Greg. Now in the next paper, do you remember the VOYAGER PAD trial? Well, it was the trial that demonstrated superiority of rivaroxaban plus aspirin versus aspirin alone to reduce major cardiac and ischemic limb events following lower extremity revascularization. Now clopidogrel is commonly used as a short term adjunct to aspirin after endovascular revascularization. However, does clopidogrel modify the efficacy and safety of rivaroxaban in this setting? Well, that's the question that today's paper is addressing and it is led by corresponding author, Dr. Hiatt from University of Colorado School of Medicine. Dr. Greg Hundley : What did they find, Carolyn? Dr. Carolyn Lam : Well in the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia, regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use as well, but with a trend for more ISTH major bleeding with clopidogrel use more than 30 days than a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization, regardless of concomitant clopidogrel with a short course of less than 30 days associated with less bleeding. Dr. Greg Hundley : Very nice, Carolyn. Well, my next paper comes to us from Dr. Hinson from the Jackson Laboratory for Genomic Medicine. Carolyn this paper focuses on a particularly challenging heart failure associated sarcomere gene, cardiac troponin T, that is encoded by TNNT2. Remember Carolyn, this is a thin filament protein that functions in the tripartite troponin complex, where calcium binds and triggers twitch force. Relative to other sarcomere genes, pathogenic TNNT2 variants are associated with poor prognosis as they carry an increased risk of sudden cardiac death that is disproportional to myocardial remodeling. The investigators used human pluripotent stem cell derived cardiomyocytes in cardiac microtissue and single cell assays and functionally interrogated 51 TNNT2 variants, including 30 pathogenic likely pathogenic variants and 21 variants of unknown significance called VUSs. They utilized RNA sequencing to determine the transcriptomic consequences of pathogenic TNNT2 variants. Dr. Carolyn Lam : Wow. And so what were those consequences, Greg? Dr. Greg Hundley : They found that hypertrophic cardiomyopathy associated TNNT2 variants increased cardiac microtissue contraction while dilated cardiomyopathy associated variants caused decreased contraction. Both of which parallel changes in myofilament calcium affinity. Transcriptomic changes, including NPPB levels, directly correlated with sarcomere function and could be utilized to predict TNNT2 variant pathogenicity. In summary Carolyn, this research found that number one, inheritance of pathogenic TNNT2 variance is a leading cause of cardiomyopathy and number two, the majority of TNNT2 variants identified in the human population are classified as those VUSs or variants of unknown significance, which limits their clinical utility in genetic testing. As such, reclassification of TNNT2 variants would improve cardiomyopathy risk determination and treatment responses for individuals harboring these variants. Dr. Carolyn Lam : Nice. Thank you, Greg. Well, in this next paper, I think the title summarizes it all: “Is There a Sex Gap in Surviving an Acute Coronary Syndrome or Subsequent Development of Heart Failure?” Well, Dr. Justin Ezekowitz from Vigor Center, University of Alberta in Canada and his colleagues used a large population based cohort of more than 45,000 patients with MI between April 2002 and March 2016, to examine the incidence and geographic findings, treatment and clinical outcomes of patients with a first time and MI. To elucidate the difference between sexes, a series of multi-variable models were created to explore all MI and non-ST elevation MI versus ST elevation MI over time. Dr. Greg Hundley : What did they find Carolyn? Dr. Carolyn Lam : Well, some attenuation of differences in clinical outcomes over time had occurred. Women maintained a higher risk than men of dying or developing heart failure in the subsequent five years post both STEMI or non-STEMI, even after accounting for differences in angiographic findings, revascularization and other confounders. Dr. Greg Hundley : Well, Carolyn, how about we get to some of the other articles in the issue. And I've got a really nice Research Letter from Professor Damien Bonnet entitled, “Addition of Corticosteroids to Immune Globulins is Associated with Recovery of Cardiac Function in Multi-inflammatory Syndrome in Children.” There's also a Research Letter from Professor Peter van der Meer entitled, “Human Pluripotent Stem Cell Derived Cardiomyocytes of Peripartum Cardiomyopathy Patients Reveal at Aberrant Regulation in Lipid Metabolism.” And Carolyn, finally I have an ECG Challenge entitled, “Wide QRS Complex Tachycardia in a Young Pregnant Woman, is it SVT or VT?” The age old question from Dr. Gunaseelan. Dr. Carolyn Lam : Nice. Well, there's also an exchange of letters between Drs. Ross and Loupy regarding the article, “Identification and Characterization of Trajectories of Cardiac Allograft Vasculopathy after Heart Transplantation: a Population Based Study,” and a beautiful Perspective piece by Dr. Verma entitled, “Two Tales, One Story and that is talking about the EMPEROR-reduced and DAPA-HF trials.” A beautiful summary there. Let's get on now though to that feature discussion. Shall we, Greg? Dr. Greg Hundley : You bet looking forward to it. Dr. Carolyn Lam : Transcatheter aortic valve replacement or TAVR has indeed become an established alternative to surgical aortic valve replacement for patients with severe aortic stenosis. Now, while the TAVR usage has increased, so has surgical TAVR valve explantation. However, that's not been really well described its clinical impact or outcomes well until today's research letter in Circulation, which represents the largest series of TAVR explants from a national database. And I'm so pleased to have with us the first and corresponding author, Dr. Shinichi Fukuhara from University of Michigan to describe the study as well as our associate editor, Dr. Tim Gardner from University of Pennsylvania. Welcome, gentlemen. Shinichi, if you don't mind for non-interventionists and non-surgeons like myself, why would you need to explant TAVR in the first place? Maybe you could start with that and then tell us about your study. Dr. Shinichi Fukuhara: First of all, thank you so much for the kind invitation. It's a great honor to be with you and Dr. Gardener. That's a very good question and a very timely question actually. When we started implanting TAVR valves probably about nine years ago or so, that was when the TAVR valve was FDA approved, we were not thinking about second TAVR procedure after the initial TAVR valve fails. And then as time goes on, we started to recognizing, some patients' TAVR valves started failing and these failure patterns can be paravalvular leak, can be structural valve degeneration, can be endocarditis. Not all patients with a failing TAVR valve can be treated with a second TAVR valve procedure and the most common driving factor at least in my program at the University of Michigan is unsuitable anatomy for a second TAVR valve and the most common anatomy pattern is a risk of a coronary artery obstruction by the second TAVR valve. These are the common scenarios where patients need TAVR valve explantation scenarios. Dr. Carolyn Lam : Thank you so much for that as a background. And as you nicely set up in your paper, as we do more TAVR, obviously there are going to be more situations like this. Please tell us what you found. Dr. Shinichi Fukuhara: First of all, what we found from this project, first, surgical TAVR valve explant procedure is not as simple as people thought it would be. I remember back in 2014, 2015 when I was still a trainee, people were talking about, which is better TAVR SAVR TAVR or SAVR TAVR SAVR? However, based on what we are just starting to see, TAVR SAVR sequence may not be a good option for younger people based on the present study data. The fact that more than 50% of patients who require the major simultaneous procedures such as aortic repair and the mitral procedures is a something TAVR implanters in our community should be more aware. Tim Gardner: I think it's very important for Shinichi to tell us to emphasize the mortality rate that you saw with the SAVRs following TAVR because that's really, I think the sobering information here. This is not comparable to doing a redo aortic valve or redo SAVR. Just tell us about that, Shinichi. Dr. Shinichi Fukuhara: First of all, these STS database. We have a STS predicted risk of a mortality, which is available for patients undergoing isolated SAVR procedure. And then based on the even isolated the SAVR procedure, the OE ratio of observed to expected mortality ratio was actually higher than 1.5 for isolated SAVR procedure in patients requiring TAVR explant. More importantly, patients who are requiring TAVR explanted SAVR, as well as a concomitant cardiac procedure are demonstrating almost close to 20% mortality rate, which is to me very striking after we analyze that data set. And this is something our community, the TAVR implanters in our community should keep in mind. Dr. Timothy Gardner: Yeah. Obviously not only is the surgery, the removal of the TAVR device and replacement with a surgical valve, not only is that complex anatomically and technically, but the associated mortality seen in this series of patients that they reported is higher than expected and actually quite high in terms of absolute operative or hospital mortality. I take this important research letter as a sort of a warning message to all of us, in particular, the cardiology community, to realize that once a TAVR valve is placed, it is more difficult and riskier to remove that and replace it with a surgical aortic valve replacement, if for some reasons such as endocarditis or valve failure or whatever comes to play. Dr. Timothy Gardner: And obviously as Shinichi has already said, when you're looking at a younger patient, patient under 60 for example, who needs an aortic valve procedure, you need to keep in mind whether as he said earlier, it's might be safer to do a SAVR first. And then if there's another procedure required, that could be because of valve failure, a TAVR could be done rather than just assuming that the TAVR is going to be there and that it can be easily replaced or taken care of. At any rate, I think that's the very important point of this paper. And I think this is really the first report and not only by the way, does it show that this is happening, but in the most recent year of your report, Shinichi, how many SAVRs after TAVR were reported, number of cases? Dr. Shinichi Fukuhara: The 2018, the last year of this study period was actually the highest obviously and it was a close to 300 cases reported. And then the number of case is a steeply increasing as I demonstrated in the figure one in the paper. Dr. Timothy Gardner: That really emphasizes obviously TAVR volume is increasing. TAVR is now being placed in younger patients who have perhaps a greater chance of requiring a second procedure. And if it has to be explantation of the TAVR because of the complexity and the inability to use another TAVR to fix the valve, the technical challenges and the operative risks are much higher. Dr. Timothy Gardner: Well, I just think that this is a warning call that we have to be realistic about the secondary requirements for patients that have TAVR and we don't yet even have a much more than a 10 year experience with TAVRs and we're seeing an increasing number of patients just in the STS database who are having to come back for TAVR explant and it's a difficult, challenging procedure. One point that Shinichi made in his article is that this technical challenge of TAVR explant may be something patients requiring this procedure may need to be referred to surgeons and hospitals with high aortic surgery volume. This is not necessarily a procedure that a surgeon can get experienced with and comfortable with doing two or three a year. That's another bit of the message here. Dr. Carolyn Lam : Thanks, Tim. And Shinichi, what would be your take home message to the clinical community listening in? Dr. Shinichi Fukuhara: Thank you so much. Yeah, this is a little bit redundant statement, but I think that another important message from this paper is that these low risk younger patients choosing to have a TAVR procedure as the initial valve therapy should be informed of the future procedure risks of a TAVR explant which frequently requires more of device explanating and the possible unplanned concurrent procedures and for these reasons careful assessment of aortic root anatomy and the feasibility of a repeat TAVR procedure should be part of with the initial TAVR workup. If we decide to proceed with TAVR for younger patients and then therefore heart team approach remains extremely important in the TAVR practice, that's my take home message. Dr. Timothy Gardner: And I'd like to reinforce that. This is, as we know, the heart team concept has been so important in providing optimal care for patients with aortic valve disease and this is a reminder of part of the discussion that should be happening at the heart team level. Dr. Carolyn Lam : Thank you so much. Clear take home messages that you've got right here on Circulation on the Run. Dr. Greg Hundley : This program is copyright the American Heart Association, 2020.  

Episode 48 BEaTS Research Radio - Interview with Dr. Benjamin Hibbert. Hallie Arnott from the University of Ottawa talks to Dr. Benjamin Hibbert from the University of Ottawa Heart Institute about how experimental Medicine in Interventional Cardiology can help to accelerate clinical translation. Tune in to learn about what experimental medicine is and how it can be used to expedite bench to bedside translation. Learn more about Dr. Benjamin Hibbert here: https://www.ottawaheart.ca/physician-researcher-profile/hibbert-benjamin

Episode 46 BEaTS Research Radio - Interview with Dr. Christina L. Luong. Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Christina L. Luong from University of British Columbia to discuss how Artificial Intelligence is, and will continue, revolutionizing cardiac care and patient outcome.Learn more: https://drchristinaluong.com/

Despite widespread acknowledgment that self-care is an essential component of sustainable practice for mental health professionals, it is an area where many clinicians struggle to implement consistent healthy habits or necessary behavioural change. In 2019, Drs. Karen G. Dyck, C.Psych and Melissa Tiessen, C.Psych became the co-founders of the website Intentional Therapist and since then, have been actively engaged in efforts to help female mental health professionals find convenient, intentional, creative, and playful ways to incorporate self-care into their lives. On the podcast we explore: their motivation to create the Intentional Therapist initiative and how they define self-carewhy they place an emphasis on female mental health professionals specifically & relevant gender differences when it comes to self-carekey components/messages shared through their newsletteraspects of their messaging that have been especially relevant to them personallythe upcoming Intentional Therapist retreat shifts in their own thinking about self-care since starting the Intentional Therapista broader discussion of self-care beyond the Intentional TherapistDr. Karen G. Dyck completed her Master’s Degree in Developmental Psychology at the University of Manitoba and her Doctoral Degree in Clinical Psychology at the University of South Dakota. She was an Associate Professor in the Department of Clinical Health Psychology at the University of Manitoba for 17 years, 4 of which she served as the Director of the Rural and Northern Psychology Programme. Within this position Karen had the opportunity to work collaboratively with a range of healthcare providers and administrators and to regularly consult with other mental health professionals. It is within that context that Karen became interested in the topics of healthy workplaces, employee wellness, and self-care. Karen left her university position in 2014 to pursue private practice and explore other, less traditional, opportunities where she could draw from her training and experience. Karen has two wonderful bonus children and lives in Anola, MB, with her supportive husband and 18 year old cat, Kittie Pie. OICBT Psychologist Dr. Melissa Tiessen completed her Doctoral Degree in Clinical Psychology at McGill University. She completed a post-doctoral residency in the Department of Clinical Health Psychology at the University of Manitoba within the Rural and Northern Program, where she had the fortunate opportunity to work under Dr. Karen Dyck. Melissa went on to work as an Assistant Professor in the Department for 2 years, and then moved to Ottawa where she worked for 1 year within the Cardiac Rehabilitation Program of The Ottawa Hospital/University of Ottawa Heart Institute. This led to a unique opportunity as the Director of the Education Directorate of the Canadian Psychological Association, where Melissa served for 4 years, overseeing the association’s national accreditation and continuing education programs. Working in the field of accreditation highlighted for Melissa the incredible importance of quality training experiences for psychology students and the necessity of good work-life balance and self-care. Melissa also had the opportunity to spend some time living abroad, where she was involved with multiple non-profit organizations dedicated to supporting the health and well-being of women and children. Since 2018 Melissa has worked in private practice. Melissa lives in Ottawa, ON, with her supportive husband and young son. https://www.intentionaltherapist.ca

Lianne is someone that I wanted to interview from day one of deciding to do this podcast. She is inspirational and I was fascinated to hear her back story and why she decided to switch from a super succesfull career on tv for so many years to creating her own podcast focused of health and wellness. She discusses how she learnt so much from her own guests and it helped her improve her own life. We discuss how she was head hunted for the numerous position titles she caries at the Ottawa Heart Institute. We cover philanthropy, volunteering, raising money, donating and her vast network of contacts through the years of media related positions she has held. Health and wellness being paramount to her were topics we covered including the death of her father and making time. Meditiation has been something she added into her life on a daily basis and we go over simple things everyone can do to improve their daily lives. An inspiring convo of focusing your life, being healthy, not letting fear stop you from following your dreams, living your best life, taking care of yourself and so so so much more.

In the first of a two part conversation, Jason and Dr. Hsu sit down with Dr. Vincent Chan, cardiac surgeon from the University of Ottawa Heart Institute and Assistant Professor in the Department of Surgery at the University of Ottawa. They talk about Dr. Chan's career, from how he got interested in cardiac surgery to the present day, exploring the long hours and sleepless nights of a surgeon's life. Music: I Dunno by Grapes http://ccmixter.org/files/grapes/16626. Flying High by FREDJI https://soundcloud.com/fredjimusic --- Send in a voice message: https://anchor.fm/whatsupdocs/message

Episode 41 BEaTS Research Radio - Interview with Dr. Jason Zelt. Hallie Arnott from the University of Ottawa talks to Dr. Jason Zelt Trainee of the Year 2019 at the University of Ottawa Heart Institute. Tune in to learn about recent advances in pulmonary hypertension and cardiovascular diseases lead by Dr. Zelt.

Episode 40 BEaTS Research Radio - Interview with Dr. Jennifer ReedDr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Jennifer Reed to discuss the importance and role of physical exercise in cardiovascular health and rehabilitation. They also discuss why it is important to account for differences in exercise regimes for women and men. Tune in and learn about how physical exercise does benefit cardiovascular health. Learn more: https://www.ottawaheart.ca/research-team/exercise-physiology-and-cardiovascular-health-laboratory

Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Nabil G. Seidah from the Clinical Research Institute of Montreal to discuss Dr. Seidah’s career as a Scientist and his work on proprotein convertases. Tune in and learn about how fundamental discoveries in Science can have a tremendous impact on the development of new therapeutics for a variety of diseases.Learn more: https://ircm.qc.ca/en/research/cardiovascular-and-metabolic-diseases/biochemical-neuroendocrinology

Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. May Griffith from the University of Montreal to discuss her translational work on biosynthetic corneas. Tune in and learn about the urgent need for corneal implants and what can be done to accelerate the clinical translation of such materials. Learn more about Dr. Griffith’s work here: https://www.griffithresearch.ca/may-griffith-2

Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Elisabeth Bik to discuss on image and data manipulation in Science and how we can do better to prevent those articles to see the light in peer review Journals. Learn more about Dr. Bik’s work here:https://scienceintegritydigest.com/

Back in 1993, University of Ottawa Heart Institute researchers announce plans to manufacture and market the world's first permanent artificial heart. Known as the Electrohydraulic Ventricular Assist Device (EVAD), the artificial heart could be implanted entirely in the body and was the first of its kind. We spoke with Dr. Tofy Mussivand.

Hallie Arnott from the University of Ottawa Heart Institute talks to Lianne Laing to discuss how the Ottawa Heart Institute Foundation sees Research and Community involvement as pillars for providing better health care for patients. Learn more about Ottawa Heart Institute Foundation:https://foundation.ottawaheart.ca/

Hallie Arnott from the University of Ottawa Heart Institute talks to Dr. Baptiste Lacoste to discuss Dr. Lacoste's recent work on defective blood vessels in Autism and its future clinical implications. Learn more about Dr. Lacoste's work here: https://www.uottawa.ca/brain/people/lacoste-baptisteFull article here: https://www.nature.com/articles/s41593-020-0663-1

Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Peter Liu to understand the Science underlying COVID-19 and how is that connected to the cardiovascular system. Learn more about Dr. Liu's research www.ottawaheart.ca

Dr. Mo Al-Khalaf from the University of Ottawa Heart Institute talks to Dr. Cristian Andrés Zaelzer Pérez about the role importance of Science Communication and how Scientists should engage different disciplines for better connect with the community as an integral part of the process. Learn more about The Convergence Initiative founded by Dr. Cristian Andrés Zaelzer Pérez at www.convergenceinitiative.org & @InfoConvergence. Follow Dr. Zaelzer Pérez on Twitter @EoloSon

Dr. Emilio Alarcon from the University of Ottawa Heart Institute talks to D.r Cornelia Bohne about the role of mentors in Science and how those individuals are instrumental for young Scientists to find their path. Learn more about Dr. Bohne's research http://www.foto.chem.uvic.ca/

Dr Mireille Ouimet from the University of Ottawa Heart Institute talks to Dr Murray Huff about how important Mentorship is at different stages of the professional formation of Scientists. Learn more about Dr Huff’s research https://www.robarts.ca/murray-huff

Dr Emilio I. Alarcon from the University of Ottawa Heart Institute talks to Dr Douglas Manuel about the role of public health in the ongoing pandemic. Learn more about Dr Manuel’s research www.projectbiglife.ca

Dr Emilio I. Alarcon from the University of Ottawa Heart Institute talks to Dr Ebrahim Karimi about how light can be structured and used in quantum communication. Learn more about Dr Karimi's research www.sqogroup.ca

Dr. Emilio I. Alarcon from the University of Ottawa Heart Institute talks to Dr Alison Flynn about innovation in education and how that is critical under the current pandemic. Learn more about Dr. Flynn’s research at www.flynnresearchgroup.com

Dr Emilio I. Alarcon from the University of Ottawa Heart Institute talks to Dr Manisha Kulkarni about what vector-borne diseases are and how the lessons from that field can be used in predictive models of a pandemic. Learn more about Dr Kulkarni’s research www.globalhealthepi.com

Dr. Robert Roberts is THE Cardiologist...and we say THE because he is the Cardiologist who brought molecular biology and genetics to heart disease. He has been known to save the Prince of Saudi Arabia's life, he co discovered more than 60 genes related to coronary artery disease, was the lead consult for NASA and developed the quantitative test that has been used to diagnose heart attacks for 3 decades. He works for the UA College of Medicine but before that he lead the cardiology department at Baylor College of Medicine in Houston for 23 years before becoming the President and CEO of the University of Ottawa Heart Institute. AND NOW A PROUD MEMBER OF THE JAKD FAMILY. Because as we all know...we are Just A Kouple Dudes...

Dr Emilio I. Alarcon from the University of Ottawa Heart Institute talks to Dr mo Al-Khalaf about how Social Media is a powerful tool for connecting Scientists with other researchers and our communities.

Dr. Mohammad Al-khalaf, a post-doctoral researcher at the University of Ottawa Heart Institute, talks to Dr Alejandro Adem about how Mathematics is the universal language of Science and how innovation in Research is vital for impacting our communities

Hallie Arnott interviews Dr Thais Coutinho Chief, Division of Cardiac Prevention and Rehabilitation & Chair, Canadian Women's Heart Health Centre at the University of Ottawa Heart Institute. Dr Couthino shares with us her opinion on the challenges and opportunities of Women in the Cardiovascular research field. Also, she discussed the importance of gender-specific research for Women's Cardiovascular Health

Janïs Petit interviews Dr. Marc Ruel, Chief of Cardiac Surgery at the University of Ottawa Heart Institute. Dr. Ruel shares with us his experience in translational medicine for developing novel materials and therapeutics in cardiac repair.

Dr Mohammad Al-Khalaf from the University of Ottawa Heart Institute interviews Dr Juan Scaiano, Canada Research Chair in Applied Photochemistry about his ongoing research on expanding the use of sunlight for practical uses in communities including regions in Africa.

Hallie Arnott interviews Dr. Emilio I. Alarcon from the University of Ottawa Heart Institute and recipient of the Investigator of Year award to learn more on how interdisciplinary Science has played a key role in his research program.

Hallie Arnott interviews Dr Erin Mulvihill from the University of Ottawa Heart Institute and the BMI Department at University of Ottawa. The role of peptide-hormones and of interdisciplinary research are discussed in this interview.

Hallie Arnott interviews Dr Benjamin Rotstein from the University of Ottawa Heart Institute about the development of new radioactive molecules for imaging the heart

Hallie Arnott interviews Dr Jodi Edwards from the University of Ottawa Heart Institute and discusses the role of brain-heart connection in cardiovascular health

It can seem like just another trend, but people are starting to get sick. Last month, health authorities in Illinois reported that a patient who vaped died after being hospitalized with a severe respiratory illness. And while that’s the first reported death, it doesn’t seem to be an isolated incident. The Washington Post has reported that there are 354 possible cases of vaping relate-lung illnesses across 29 states. Although there haven’t been any clusters of lung illnesses related to vaping reported in Canada, health experts in this country are watching the situation closely. The number of Canadian teens using e-cigarettes has risen quickly, up 74 percent between 2017 and 2018. Host Tamara Khandaker is joined by Dr. Andrew Pipe of the University of Ottawa Heart Institute. They talk about what we know about the situation in the U.S. so far, how e-cigarettes work, and why vaping could actually be increasing the smoking rate among young Canadians.

For years, daily low-dose aspirin was being prescribed as a magic bullet to prevent heart attacks, strokes and other cardiovascular disease. Older Canadians were advised to undertake this regimen whether they had heart problems or not. Now there is evidence that the risks outweigh the benefits. The American Heart Association released the new guidelines and Libby reached Dr. Marc Ruel at the Ottawa Heart Institute to discuss. And - call it a manual with everything you need to know to push back against ageism. Author Ashton Applewhite says she wanted to erase many of the myths about later life. Libby reached her in NYC.

For years, daily low-dose aspirin was being prescribed as a magic bullet to prevent heart attacks, strokes and other cardiovascular disease. Older Canadians were advised to undertake this regimen whether they had heart problems or not. Now there is evidence that the risks outweigh the benefits. The American Heart Association released the new guidelines and Libby reached Dr. Marc Ruel at the Ottawa Heart Institute to discuss. And - call it a manual with everything you need to know to push back against ageism. Author Ashton Applewhite says she wanted to erase many of the myths about later life. Libby reached her in NYC.

This week, I was beyond thrilled that Dr. Thais Coutinho from the Ottawa Heart Institute took time out of her schedule to tape our podcast. Dr. Coutinho is a cardiologist, who is working as Chief, Division of prevention and rehabilitation at the Ottawa Heart Institute as well as the Chair of the Canadian Women's Heart Health Center. Heart disease is the number one killer for women. This podcast covers the real differences between men and women when it comes to this disease, the critical preventative factors for avoiding heart disease and just how seriously we need to take the indicators. My hope is that you listen to the podcast with the intent to make changes. This disease is preventable for many.

Gary Newton, in an interview with Ross Upshur, discusses his agenda as the Chief Executive Officer of the Toronto Sinai Health System while explaining his views on complex care and how he is trying to bring about change in Sinai Health System in Toronto. In this fascinating and  candid interview, Dr. Gary Newton talks about his views towards complexity, his aha moments, his involvement in health administration, his experience of running a hospital based Division of Cardiology,  the Department of Medicine and ultimately to his role as the CEO of Sinai Health System after the merger of Bridgepoint Active Healthcare and Mount Sinai Hospital in 2015. Dr. Newton discusses the challenges of managing the process delivering care to individual patients to managing populations of patients with complexity, while helping complex health systems evolve. He further explains the shortcomings with the current “non-system system”. Gary Newton assumed the role of President and CEO of Sinai Health System in October 20161. He previously held the position of Physician-in-Chief of Mount Sinai Hospital from 2013 to 2015, and was appointed to the role of Chief Medical Strategy Officer and Physician-in-Chief of the newly formed Sinai Health System in 2015. As a practicing Cardiologist, he was Head of the Division of Cardiology, University Health Network and Mount Sinai Hospital from 2009 through 2013. He has had an active research program in human physiology, focusing on congestive heart failure, most recently investigating nutritional issues in patients with heart failure. He currently serves as Vice-Chair of the Scientific Research Committee of the Heart and Stroke Foundation of Canada. Gary is a graduate of the University of Toronto Medical School. He completed internal medicine at the University of Toronto, and trained in adult cardiology at the University of Ottawa Heart Institute. He has worked at Mount Sinai Hospital since 19872. For a full bio, please click here. Some of the articles authored by Gary Newton indexed in PubMed. “There is just no better place to work” Dr. Gary Newton reflects on his first year as President and CEO Courtesy of Sinai Health System website.

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.                                                 This week's journal is really special. It is the 2017 cardiovascular surgery-themed issue of "Circulation." To summarize this issue, I am so privileged to have the editors, Dr. Marc Ruel from University of Ottawa Heart Institute, as well as Dr. Timothy Gardner from Christiana Care Health System. Welcome gentleman. Dr. Timothy Gardner:     Hello. Dr. Marc Ruel:                   Hi, Carolyn. Glad to be here. Dr. Carolyn Lam:               Thank you for another beautiful themed issue, Marc. I see that there are four general themes within this theme, if I may. The first of which are a collection of papers on coronary disease and coronary surgery. Could you maybe start by giving us an overview of that? Dr. Marc Ruel:                   One of the main topics that have been looked at in the surgical-themed issue this year is coronary surgery. We all know well that 2016, 2017, the academic year was quite fertile in providing new information around coronary surgery, especially with the release of the ART trial had actually scientific sessions of the American Heart Association the last November with simultaneous publication.                                                 Interestingly, the cardiovascular surgical-themed issue has several coronary papers and one that deals with essentially with graft failure, if you will. There's an in-depth review written by Mario Gaudino, who is well known and does fantastic work at Cornell, who essentially put a team together looking at several aspects of coronary graft failure. I guess we can say that these are looked in quite great depth, and they deal with several aspects of what would lead to a coronary bypass graft to fail.                                                 First and foremost, Mario and the team look at the blood components. Then the artery and the native bed itself. Then they focus a lot on the conduit, not only the nature of the conduit being a venous versus arterial conduit, but also the way of storing the conduit prior to performing the bypass. Also, the technique that's used around the use of that conduit.                                                 Finally, I'd say that the review culminates with the patient bioreactor, for lack of a better term, aspect. Endothelial dysfunction in the patient with diabetes, age, gender, hypertension, dyslipidemia, etc., all these things that do act as a significant substrate for the fate of the conduit vessel.                                                 A very unique, I think, first-time, in-depth review that, certainly, the "Circulation" editorial team and reviewers were very excited about. I think this will be quite impactful and provide very, very detailed information for future research and future improvement and fate of the coronary graft conduits. Dr. Carolyn Lam:               And, Dude, I agree. It's the new look at perhaps a classic, old, central surgery, the cardiovascular surgery. Very nice, indeed. Dr. Marc Ruel:                   Precisely, thank you. We also have a couple of important, seminal original papers within the realm of coronary surgery. In fact, these also deal, to some extent, with the fate of conduits and certainly how they work in the patient population in long ago bypass surgery.                                                 One is a randomized control trial, a single center randomized control trial that was performed in South Manchester. It's called the VICO trial, a study comparing vein integrity and clinical outcomes. Essentially, the study looked at open vein harvesting versus two types of endoscopic vein harvesting for coronary artery bypass grafting.                                                 The study was performed at a single center in England with three sound methods, having three groups of 100 patients who were compared with regards to the vein harvest technique. The primary outcome was with regards to actual vein integrity, looking at muscular damage and endothelial function and integrity on microscopy.                                                 Surprisingly and actually quite reassuredly that there were very few differences between endoscopic vein harvest and open vein harvest. Certainly the investigators also looked, as one of their secondary outcomes, at quality of life. It was quality of life that was gained in patients who had endoscopic vein harvest versus those who had open vein harvest.                                                 Overall, there was no difference in major adverse cardiac events. Therefore, showing at least in an internally valid fashion that these investigators at their center could do endoscopic vein harvesting as well as open vein harvesting. Dr. Carolyn Lam:               I know that there are other original research papers, perhaps. Would you like to highlight any of them? Dr. Marc Ruel:                   Yes, for sure. Carolyn, there's also one more coronary surgery paper, which I wanted to highlight and that is the paper entitled, "Does Use of Bilateral Internal Mammary Artery Grafting Reduce Long-Term Risk of Repeat Coronary Revascularization?"                                                 This is a multi-center analysis with first author is Iribarne from Northern New England. Essentially, seven medical centers got together and took about 20 years of consecutive CABGs with a total number of 50,000 operations, or just shy of 50,000 operations.                                                 The median duration of follow-up was 13 years, and these patients were well matched together using a propensity matching scheme. I think this paper and this research is unique and of high impact. Even though it does have shortcomings of not being a randomized control trial, it is very welcome information, especially in light of the recent ART trial, which, as you know, did not show any difference at five years analysis between single and bilateral internal thoracic artery use.                                                 The particularity of the Iribarne paper is that it is a very large data set up with close to 50,000 patients. It is multi-centered, therefore, it is real life. It is a consecutive series. The patients are extremely well matched, and it is remarkable to hear that the patients, in fact, had no difference in mortality until about five years after the operation.                                                 As opposed to many previous series where single versus bilateral internal mammary grafting shows a mortality difference very early on, which always raises the suspicion of poor matching or confounding by indication, if you will, this paper did not have that.                                                 Finally, the follow-up was quite long and at about six years, there was really a mechanistic signal with regards to repeat revascularization events, which seemed to match the difference in late mortality. There was no difference in early and five-year mortality, but afterwards as repeat revascularization events started to occur more frequently in the single mammary group, this was matched by a difference in mortality, as well.                                                 I think a very useful, large, long follow-up mechanistically-based information that I think adds very significantly to the current information we have about bilateral versus single mammary use. Dr. Carolyn Lam:               Thank you, Marc. Two original papers, highlighted, dealing with really very important modern controversies in this area. Open vein versus endoscopic vein harvesting, single versus bilateral mammary artery bypass. Excellent.                                                 Let's move on now to the next sub-theme, if you will. And that is the collection of papers on "Adult Congenital Heart Conditions," really, really an increasingly important and growing population that we're seeing. Tim, would you like to summarize maybe some of the highlights of the papers there? Dr. Timothy Gardner:     The first paper, as you point out, is focused on adult patients with repaired tetralogy of Fallot. This series came from the UK and it examines the course of almost 60 patients, at a mean age of 35 years following a repair of tetralogy as infants or young children, developed right heart failure and required pulmonary valve replacement.                                                 This is a common scenario that we're seeing, successfully repaired children who appear to do well but as they get into their late 20s and 30s, their pulmonary valve function, which is often inadequate or not even present valve, require an intervention.                                                 The important learning here is that pulmonary valve replacement, either surgically or by catheter technique, was shown to be highly effective in salvaging right ventricular function. That is based on imaging studies as well as hemodynamic studies of right ventricular function. There was an almost, in this group of patients, almost an immediate reverse remodeling of the right ventricle after placement of the valve, that continued to improve over time.                                                 This was, I think, quite reassuring. There, historically, was a bit of a reluctance to operate on these patients as their right heart was failing, despite the fact that without some intervention to take the volume load off of the RV, the patients didn't do well. This is good news for an important group of patients who we are all seeing, who oftentimes present to the adult cardiologist because of this right ventricular failure problem. A nice, reassuring study.                                                 Actually, the other two congenital papers are, again, focused on the infant. They both deal with the infant with hypoplastic left heart syndrome or single ventricle pathology. The first paper seems sort of specialized in terms of its focus, "The Optimal Timing of Stage-2-Palliation for Hypoplastic Left Heart Syndrome." This was a report from the NIH Pediatric Heart Network. They had a single ventricle reconstruction trial.                                                 This network is comprised of about 10 North American centers, both in the U.S. and Canada and has provided excellent data about the management of pediatric heart disease but, in particular, the single ventricle trial has been excellent.                                                 In this particular paper, they look at the optimal timing for stage-2 repair. Just to remind ourselves, the first part of the three-stage treatment for hypoplastic left heart syndrome is the Norwood procedure, which has to be done shortly after birth, as the patent ductus arteriosus closes and converts, essentially, the single right ventricle into the systemic ventricle.                                                 The stage-2 comes along, usually done with a Glenn-type of shunt, increases pulmonary blood flow and stabilizes these infants until they can reach the age for, and the heart function for definitive repair. This has been a particularly difficult problem for the congenital heart surgeons. What is the optimal timing?                                                 This study, which involved over 400 patients, identified optimal timing for the second stage between three and six months after the Norwood. I think this was very reassuring, is reassuring or supportive for the congenital heart community in terms of both patients and also good evidence base that a delay of three to six months does, in fact, produce the best transplant-free survival.                                                 In fact, the other aspect of this observation was that infants who developed the need for another second stage operation sooner than that did not do well, and the reasons for the required earlier surgery could be failure of the initial operation or additional anatomic risk factors. But this, I think, was an important, large series, multi-center study that will prove to be very helpful in sorting out this complex timing of a three-stage repair.                                                 Just to comment, again, for readers who don't deal with infant congenital heart treatments very often, there's been a remarkable amount of success over the last two decades in salvaging and saving these very difficult infants with the hypoplastic left heart syndrome. In fact, an additional paper in this surgery-themed issue, comes from the UK and is, in fact, a report on the findings from the UK-wide audit of the treatment of infants with hypoplastic left heart syndrome.                                                 In fact, their findings, in this sort of real world, not in the Pediatric Heart Network trial group, is very similar. They found that infants who got to the second stage without additional refinement of the initial Norwood procedure and were able to be successfully treated with a Glenn shunt somewhere in the four-to-six-month age range, did well. They actually made the point that the anatomy was more of a determinant than anything else.                                                 I think that this particular review will reinforce what the congenital heart surgeons have learned about optimal timing for this three-stage treatment of what previously were unreconstructable children. Dr. Carolyn Lam:               Thank you so much, Tim. Isn't it wonderful the way papers come in and they're actually complementary and consistent with one another. We're just so lucky to be publishing all of these great, high-quality, impactful papers in "Circulation."                                                 Moving on, the next paper actually reminds us why this is a cardiovascular surgery-themed issue and not just a cardiac surgery-themed issue. Didn't we just say that earlier, Marc? This one is on abdominal aortic aneurysm treatment. A population-based landscape of this. Could you tell us a little bit more about that one? Dr. Marc Ruel:                   Absolutely. Carolyn, you're entirely right. We must remember that "Circulation" is also about peripheral vascular disease, saying this earlier, or cardiovascular surgery and anesthesia consult also when it encompasses vascular surgery. Precisely to that effect, one of the papers in our cardiovascular surgical-themed issue is a landscape population based analysis from Finland that looks at the incidence of abdominal aortic aneurysm between the years of 2000 and 2014.                                                 Finland has a population of about 5.5 million and remarkably has a very circumscribed healthcare system. They do not have an organized system of AAA care as some other countries have shown to have and potentially benefit from, but rather they have a treatment of this condition at several institutions, many of which may not be high volume.                                                 I think the paper is remarkable is that it is very well nested in terms of a population. It provides a comprehensive landscape of where this condition has evolved to over the last few years. Obviously, we see in the results from the authors that the mortality has decreased quite a bit, but also the incidence, probably as a result of better control of risk factors. And also the incidence of rupture outside the hospital.                                                 One thing that came out of this paper, as well, is a potential cohort of the benefits gained from developing an organized system of AAA care, from the reason that the mortality of AAA rupture in Finland was still quite high, despite this being a modern series. In fact, when you include ruptures, before arrival to hospital and at arrival to hospital, the overall mortality was almost 80% for ruptured AAA.                                                 Perhaps one message that comes out of this is that there may be a benefit in having specialized centers dealing with these conditions, especially as they are in the process of rupturing. One last observation was, obviously, the increasingly prevailing role of endoscopic vascular repair in the treatment of this condition, which, in fact, has now surpassed open repair as the dominant method of elective repair.                                                 I think, overall, a very comprehensive, well-nested, country-wide with good follow-up landscape of the AAA condition in a country that has essentially a similar socioeconomic status to much of the western world. Therefore, with external generalized ability to some extent. Dr. Carolyn Lam:               Exactly, and contemporary data. I really enjoyed that you paired those with an excellent editorial, as well. Finally, before we wrap this up, I have to ask Tim to comment on this next paper, and it's on ventricular assist device malfunctions, I love the title, "It's More Than Just The Pump." Of course, as a heart failure physician, this one's very close to my heart. Forgive the pun. But, Tim, could you tell us about that? Dr. Timothy Gardner:     This paper comes from the University of Pittsburgh and their artificial heart program. Robert Kormos is the first author and he's been one of the stalwart leaders in the use of LVADs and other pump devices. He reports on their experience with over 200 both HeartMate and HeartWare ventricular assist devices.                                                 It was interesting when we reviewed this paper by the editors, there was some thought that maybe this was a little too engineering focused and so on, but I think the point of the paper is that, as they say in the very first line in their report, reports of LVAD malfunction had focused on pump thrombosis.                                                 But they point out very appropriately that, in fact, controller failure, battery failure, cable failure and other causes of device failure, which can be critical and life threatening and so on, are engineering issues. It reminds us that when we're managing this difficult group of patients, and we're seeing many more patients today with getting LVADs than 10 or 20 years ago, we need to have the bioengineering abilities and resources available.                                                 Even the surgeon and the critical care physician who is dealing with these patients either has to acquire this kind of knowledge or capacity himself or herself, or needs to have a good bioengineer nearby.                                                 What's interesting, I think, that all of us define that these mechanical failures were more common in this pretty big experience than what we've more clinically worried about, which was thrombosis of the pump. Dr. Carolyn Lam:               Exactly. That's so wonderful. And you know it just leads me to really thank you both, Marc and Tim, for this extraordinarily excellent selection of original research, state-of-the-art and perspective articles and editorials on congenital, coronary, vascular and heart failure surgery. This really appeals not just to the cardiovascular surgeons but really to the vast readership of "Circulation."                                                 Thank you for a wonderful themed issue and thank you for this great podcast. Dr. Timothy Gardner:     Well, thank you. Dr. Marc Ruel:                   Thank you very much, Carolyn. Dr. Carolyn Lam:               Listeners, don't forget to tune in again next week.

  Carolyn: 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. We have such a special podcast for you today. The entire podcast is going to be a conversation with two very special guests, Dr. Marc Ruel from The University of Ottawa Heart Institute, the guest editor of the surgery themed issue this week. Hi Marc.   Marc: Hello Carolyn. How are you?   Carolyn: Very good. Especially because we also have Dr. Timothy Gardner, Surgeon, Associate Editor from Christiana Care Health System. Welcome back again, Tim.   Timothy: Thank you, Carolyn. Glad to be here.   Carolyn: Marc, could you first give us an overview of the surgery themed issue from your perspective.   Marc: This year as we have had on previous years, we are having a surgery themed issue which comprises what I would argue which is some of the very best cardiac surgical science can offer to the wide readership in the cardiovascular community that served by circulation. This year, we will have a total of ten articles that would be published in circulation, as a section of one of our regular issues and out of those ten, there are five original papers. There's one research letter which is an original research article but in a shorter format and we'll also have one invited perspective paper namely about coronary artery bypass grafting and its future with respect to multi-arterial grafts and the themed issue will be completed by three state of the art papers that deal in a very in depth comprehensive way with some important problems that the cardiovascular community faces from a clinical point of view.   Carolyn: Thanks Marc. That was a beautiful summary of the issue. I couldn't help but notice that there was a theme of coronary artery bypass surgery covering at least four of the papers and I really like your thoughts on that. You covered everything from medical therapy, CABG versus PCI, on versus off-pump, emergency surgery in the setting of shock. Could you go through each of these four papers a little and tell us what was your take home message from each?   Marc: As you said, there are three original research articles and one invited perspective that relate to coronary artery bypass grafting surgery and these encompass the number of clinical problems that are still controversial and certainly I believe they contribute a very, very significant [inaudible 00:02:31] with the wealth of knowledge that the cardiovascular community is looking for at this point. If I may go one by one, just with a very high level overview, if you will. The first one is a paper from the Leipzig Heart Center with first author, [Pieroz Adewalla 00:02:45], which looked at surgery for acute myocardial infarction but accompanied with cardiogenic shock. As you know, many patients undergo surgery in an acute MI context, but surgery for cardiogenic shock is often a very gruesome difficult decision.     Leipzig Heart Center looked at over 3,000 patients who had an acute MI prior to cardiac surgery for bypass surgery and of these, there were 508 patients who actually had cardiogenic shock due to [valve 00:03:15] failure with myocardial dysfunction and to give you an idea, these patients were quite sick. There's about 40% of the patients who were ventilated prior to surgery or very close to 40%. The timing was quite urgent, those patients were on inotrophes and on vasopressors to support their blood pressure prior to operation. Essentially, what they found is that first the outcomes got better over the last number of years, this is a series that dates back to about the 2000's, so the early 2000's.     They also favor an approach where they tried to avoid a cardioplegic arrest of the heart. Their favored overall approach is to do what we call on-pump beating heart type of surgery which would be a surgery where the cardioplegia would not be administered to stop the heart but the hemodynamics would be supported for the cardio coronary bypass. They also have over the years since the beginning of this year, is in 2000 ranging up to 2014 of increasing the use of the off-pump bypass surgery and certainly the outcomes have been better and the mortality although high has decreased significantly. It was as high as 40% in the early parts of the cohort if you will and in the latest third of the experience, therefore from 2010 to 2014, the mortality has been down to about 25%.     Again, these are patients who present with cardiogenic shock. What's also interesting to note is that patients who survive out of hospital still have a significant mortality burden and about 50% of them survive long term. What was interesting is the  Leipzig group is looking at some predictors of bad outcomes in those patients and they found that the serum lactate over four minimal per liter was actually a very robust and multi-variative predictor of a poor outcome after surgery.   Carolyn: That was a great summary of that first paper. You mentioned beating heart surgery and so on. Would you like to comment on next paper that I think was the largest single institution European study comparing on versus off-pump bypass surgery?   Marc: You're absolutely right. This is a paper from England, [inaudible 00:05:25] from Liverpool, where the patients were gathered from and with some contribution from Oxford as well from a statistical and methodological point of view and it's a retrospective cohort study of all isolated CABG patients in Liverpool between 2001 and 2015. These are bypass surgery patients and in total, there were over 13,000 patients who had CABG. About 6,000 patients had off CAB which is off-pump bypass surgery and more than 7,000 had bypass with cardiopulmonary bypass. The median follow up was 6.2 years. What's interesting in this paper is that they essentially found equivalent long term outcomes. As you know, there has been some debate regarding the completions of myocardial revascularization and the long term graft patency with off-pump surgery versus on-pump surgery. Also named conventional CABG.     What's interesting here is that the benefits of off-pump CABG appear to be seen early on with regards to antiemetic release as stroke rates, etc. Which does correspond to some of what has seen in the randomized controlled studies. However, the long term data is interesting. There's a a nice editorial about this paper written from a group from the Cleveland Clinic with Dr. Joe Sabik as the senior author and essentially it raised a number of good points, although this is an important series, it also shows that the surgeons who are very good at off-pump bypass surgery may overall be slightly technically more skilled at doing bypass surgery in itself and for instance, use more often arterial grafts and have more advanced techniques in their completion of bypass surgeries for their patients.   Carolyn: Right. I'm so glad you mentioned the editorial. I was about to bring that up as well. Switching gears to you very kindly included a paper that talked about medications and the impact of here is the medical therapy on the comparative outcomes between CABG and PCI. Would you like to discuss that paper?   Marc: This is a paper from the Care Registry which has generated some interesting publications in the past. The lead author is Dr. Paul Polinski and there's co-authors, Dr. Herbert Prince and Michael Mack from Dallas as well. This was presented at the science sessions in Orlando last November and it's an interesting paper. Essentially they have looked at large databases, again the Care Registry which comprises eight community hospitals and they look at six month period of performance of CABG and those eight community hospitals. They ended up with over 2,700 patients who were then systematically followed on a regular basis up to 2009 at which time the database was locked.     They look at various outcomes but also medication use in great detail over that period of time and the interesting perspective that this paper brings is that first, most patients at least in that period were not on optimal medical therapy. The authors used their own predefined definitions of what constitutes optimal medical therapy and this is with regards to adherence to aspirin use, lipid lowering agents, beta blockers and indicates of PCI, dual anti-platelet therapy. As expected but nicely documented in this paper, the outcomes of patients who were not on optimal medical therapy were much worse than those who were and CABG proved to be more robust in patients who were not on optimal medical therapy compared to PCI.     The differences between CABG and PCI in patients who were on optimal medical therapy tended to vanish. However, a number of caveats here is that only 25% of patients in fact in this cohort were on optimal medical therapy. The vast majority of patients were not considered to be on optimal medical therapy. Therefore, there are considerations of definitions that one has to be aware of and also considerations of statistical power because the group that was on optimal medical therapy was much smaller than the other group. Therefore, the effects, the superiority of CABG over PCI could only be firmly demonstrated in the group was not on optimal therapy, again comprising 75% of patients in this cohort.   Carolyn: I love your summaries and they really show that these are true significant original contributions to that knowledge gaps in coronary artery bypass surgery. To round it all up, you also invited a perspective on novel concepts. Would you like to comment on that paper?   Marc: This is an invited perspective in the view classifications that circulation has which is entitled, "The evolution of coronary bypass surgery will determine relevance as a standard of care for the treatment of multi-vessel CABG." It is authored by three leaders in the field, Dr. Gener, Dr. Gudino, and Dr. Grouw. Dr. Gener has been leading several of what I would call the advanced multi-vessel coronary re-vascularization trials looking for instance at multi-arterial grafts doing numerous anastomosis with two ventral mammary arteries in a wide fashion. He's been a leader of this movement certainly. Dr. Gudino recently published [inaudible 00:10:43] the 20 years of outcome of the radial artery graft and certainly has been one of the pioneers which use of this arterial graft for coronary artery bypass surgery. What the authors provide here is a very nice summary of what the trials have shown so far and they also report as many know that their rate of multi-arterial grafts use in SYNTAX, FREEDOM and I think we will soon see in EXCEL and NOBLE that will be presented this fall, has not been as high as it should have been.     In the US, it is estimated right now that the rate of use of more than one mammary artery is less than 10% across the nation, and other countries have not performed better than this either. This perspective is a call to improving the quality of multi-vessel coronary artery bypass mainly through the use of multiple arterial re-vascularization. There is also considerations around the hybrid coronary re-vascularization and as well as the use of off-pump versus on-pump surgery.   Carolyn: I am really proud and privileged to have helped to manage one of the papers as associate editors in this issue as well and that is the paper from the group with corresponding author, Dr. Veselik, from Boston Children's Hospital and it centers around patients with congenitally corrected transposition of the great arteries but a management problem that is really increasingly encountered and really needs to be reviewed properly and that is the management of systemic right ventricular failure in these patients. Tim, you were so helpful in looking at this paper as well. Could you share some of your thoughts?   Timothy: Well, this is a somewhat unique situation where a patient with this condition, congenitally corrected transposition of the great arteries may go through early life, in fact may end up as a young adult before this particular condition is identified because if there is no shunting or no cause for cyanosis and heart murmurs and so on early on, the circulations seem to work pretty well until the poorly prepared right ventricle which is the systemic ventricle, starts to fail after years of work carrying the systemic circulation and that is really the focus of the paper. There's been a lot of work and publications and attention to transposition syndromes but this particular one is a condition that may be first encountered by adult heart failure cardiologist who have not had this kind of exposure to congenital heart disease. It's a particularly apt paper to bring this condition to our attention and to demonstrate that really it's the adult heart failure cardiologist who may be managing these patients in their late 20's or 30's, when that systemic right ventricle fails because of a lack of formation to manage the systemic circulation.   Carolyn: Exactly. Written by a group that has one of the most robust experiences in this field, so that also brings to mind another state of the art article in the issue that refers to the hypoplastic left heart syndrome and though it's entitled that and people may think it's rare, I think it's increasingly being seen in the adult cardiology world as well. You want to comment on that one?   Timothy: That actually is one of the main points of this paper that this very, very difficult condition of hypoplastic left heart syndrome that requires staged operations beginning in the neonatal period has now reached the state of surgical accomplishment in medical management where many of these young children are surviving into young adulthood. Albeit, with having had two, or three, or four operations. In a community like ours here in Delaware, where pediatric patients transition to adult services and adult cardiologist sometime around their 20's, it's really important for the entire cardiology community to be aware of what has happened in terms of the successful staged treatment of children with hypoplastic left heart syndrome and that is brought out very nicely by the three authors who look at various accomplishments and different techniques for managing these staged repairs. It is very amazing to someone who has been observing this field for sometime as I have, that many of these children are in fact surviving into young adulthood and will require comprehensive cardiovascular treatment, not just by neonatal specialist but by specialist in adult congenital heart disease.   Carolyn: Exactly, which is why such a timely state of the art articles both of them for this issue. There is another state of the art article that you were handling, Tim, "The Surgical Management of Infective Endocarditis Complicated by Embolic Stroke", now that's an important topic.   Timothy: Absolutely, as we know up to a half or more of patients with infective endocarditis primarily on their left sided heart valves will have cerebral embolic problems and it has really been a dilemma for many of us in terms of optimal timing for the cardiac surgery with respect to the existence of cerebral injury from the embolism, from hemorrhage that may occur, from hemorrhage that may be exacerbated by placing the patient on the heart-lung machine, etc, and this paper really takes an extremely comprehensive, careful and judicious look at all of the evidence that has emerged and it has been a confusing field of evidence as to how to best optimally manage these patients with cerebral involvement from infective endocarditis.     I think this paper is going to have a big impact. It appears that there are a couple of messages that I took away from this paper. Number one, we really need to use the full panoply of diagnostic opportunities or diagnostic test for characterizing the nature and the extent of the cerebral involvement in these patients and then perhaps even more important, we need to convene what the authors called the infective endocarditis team and that has to include not just the surgeon, the cardiologist and the infectious disease specialist but also the neurologist, the neuro-interventional specialist, the neurosurgeon and so on because all of these specialist need to contribute to the assessment and choosing the optimal timing for these patients.     That is the central message of the paper. The authors also suggest that we may be getting to the point where we need to update and make sure that the guidelines that we're using are in fact current. Current in the sense that the experience now with advance imaging and with more aggressive management of the neurological or cerebral issues really need to be factored into how best to handle these patients, but I think this paper is going to have a big impact, it's very well written and very thorough.   Carolyn: I agree. In fact all the content we just discussed is just so rich. Congratulations on such a beautiful issue. Marc, do you have any last highlights you'd like our audience to hear about?   Marc: I'd like to also mention two other original research papers that will be featured in the surgery themed issue. One, in keeping with the congenital theme that we had talked about is about the modified [Straun's 00:19:08] procedure for palliation of severe Ebstein's anomaly and this is a series actually from Professor [Straun 00:19:16] himself mostly originating from Children's Hospital Los Angeles and essentially, the series here is that of 27 patients about equal in gender distribution who were operated at seven days of life, between 1989 and 2015.     It's very interesting that patients did well, the survival at ten years is 76% and most of them have undergone successful Fontan completion. I think this is a very important paper not only because it is an extremely vexing and difficult problem to deal with Esbtein's anomaly but it comes from the innovator of the operation himself with his team and it provides much needed data regarding the long term outcomes of these children with this very difficult solution. I think this will be of great interest and also as we commented before veering into the world of adult cardiology as well, because fortunately most of these patients survive into adulthood.     The other paper I wanted to touch upon which is also an original research paper that will be in this themed issue, is a paper from the CTSN Group looking at the impact of left ventricular to mitral valve are being mismatched on recurrent ischemic MR after ring annuloplasty and this paper used the free innovative and interesting methods. As some of you may know, there were two large files recently that were conducted by the CTSN looking at either moderate MR at the time of coronary artery bypass grafting or at severe ischemic mitral regurgitation. The randomizations were different when the moderate MR was CABG lone versus CABG post mitral valve repair and the severe MR was mitral valve repair versus mitral valve replacement.     These studies have led to interesting conclusions that several will know about but what's been interesting in the current study is that they have gathered all patients who underwent mitral valve repair from both studies, original randomized trials and they ended up with about 214 patients who underwent mitral valve repair. The others had moderate or severe MR and basically the point of this study is to look at predictors of failure of mitral valve repair and this is an extremely relevant problem, not only for the cardiac surgical community I would venture, but also for heart failure community and for JV General cardiology community. What the others found is that the most important predictor of recurrent mitral regurgitation after mitral valve repair was something called the left ventricular and systolic diameter to ring size ratio and they provide an algorithm which will have to be tested clinically with regards to whether it is applicable and indeed changes outcome, but this is a very important discovery in the field of ischemic MR and enabling us to hopefully better understand and improve outcomes for patients with this very difficult problem.   Carolyn: I agree. Thank you so much, Marc and Tim for this most insightful discussion. Thank you very much and to the listeners out there, don't forget you've been listening to Circulation on the Run. Join us next next week for more highlights and features.    

People who smoke tobacco may be interested in quitting, reducing their smoking or neither. Physicians can offer interventions for all of these groups. In this podcast interview, Dr. Robert Reid and Dr. Andrew Pipe – experts on smoking cessation from the University of Ottawa Heart Institute’s Division of Prevention and Rehabilitation – offer practical advice to guide physicians in helping their patients. They, and co-authors, have reviewed evidence on smoking cessation initiatives in an article published in CMAJ. Full review article (subscription required): www.cmaj.ca/lookup/doi/10.1503/cmaj.151510 ----------------------------------- Subscribe to CMAJ Podcasts on iTunes, Stitcher, Overcast, Instacast, or your favourite aggregator. You can also follow us directly on our SoundCloud page. Our podcasts are also released on www.cmaj.ca and on www.cmajblogs.com.

Carolyn: 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 Centre and Duke National University of Singapore. I am so excited to be joined in just a moment by Dr. Andrea [inaudible 00:00:21] and Dr. Wendy Post to discuss the feature paper this week about leisure-time physical activity and the risk of coronary heart disease in young women. First, here's the summary of this week's issue.     The first paper, by Dr. Bohula and colleagues at the TIMI Study Group at Brigham and Women's Hospital in Boston, Massachusetts, aim to test the hypothesis that an atherothrombotic risk stratification tool may be useful to identify high-risk patients who have the greatest potential for benefit from more intensive secondary preventive therapy such as treatment with Vorapaxar following a myocardial infarction. As a reminder, Vorapaxar is a first-in-class anti-platelet agent that inhibits thrombin-mediated activation of platelets via the protease activator receptor 1. The authors studied almost 8,600 stable patients with a prior myocardial infarction followed for a median of two and a half years.     In the thrombin receptor antagonist and secondary prevention of athrothrombotic ischemic events, TIMI 50 trial. They identified nine independent risk predictors which were age, diabetes, hypertension, smoking, peripheral artery disease, prior stroke, prior coronary bypass grafting, heart failure and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rates of cardiovascular death, myocardial infarction or ischemic stroke. Moreover, the net clinical outcome was increasingly favorable with Vorapaxar across the risk groups.     In summary, this paper provides a practical strategy that could be used by clinicians to assist with risk stratification and therapeutic decision-making regarding Veropaxar use for secondary prevention after myocardial infarction.     The next paper is by first author Dr. [inaudible 00:02:40] and corresponding authors, Dr. [Gerstein 00:02:43] from the Beth Israel Deaconess Medical Center and Dr. [Carr 00:02:47] from the Broad Institute of Harvard and MIT, who look at aptamer-based proteomic profiling. Now DNA aptamers are [alu 00:02:57] nucleotides of approximately 50 base pairs in length selected for their ability to bind proteins with high specificity and affinity. They therefore holds considerable promise for biomarker and pathway discovery in cardiovascular diseases.     These authors applied a novel technology that uses single-stranded DNA aptamers to measure over 1,100 proteins in a single blood sample. They applied this to a model of planned myocardial injury and that is patients undergoing septal ablation for hypertrophic cardiomyopathy, and they found that 217 proteins were significantly changed in the peripheral vein blood after planned myocardial injury in this derivation cohort. They validated 79 of these proteins in an independent cohort. Furthermore, among 40 validated proteins that increase within one hour after myocardial injury, 23 were also elevated in patients with spontaneous myocardial infarction.     Finally, the authors applied this to archive samples from the Framingham heart study and showed 156 significant protein associations with the Framingham risk score. This study is so exciting because it highlights any merging proteomics tool that captures a large number of low abundance analytes with high sensitivity and precision, thus providing important proof of principle for future clinical applications and this is discussed in an excellent editorial that accompanies this paper by doctors Graham [Malini 00:04:37], [Lau Enleui 00:04:39] from the University of Ottawa Heart Institute.     The next paper is by Dr. [Anter 00:04:51] and colleagues from the Beth Israel Deaconess Medical Center in Boston, Massachusetts, who looked at post infarction, reentrant ventricular tachycardia and addressed the problem that in vivo descriptions of ventricular tachycardia circuits are currently limited by insufficient spatiotemporal resolution. The authors therefore utilize a novel, high resolution mapping technology to characterize the electrophysiological properties of these reentrant circuits in 15 swine.     The main finding was that the zones of slow conduction within the reentrant circuits with the inward and outward curvatures while conduction velocity in the comment channel isthmus itself was nearly normal. The authors further demonstrated that entrainment mapping over estimated the true size of the isthmus. Thus, the conclusion was that high resolution activation mapping of ventricular tachycardia may better guide ablation therapy and ablation at zones of high curvature may be an attractive target for ablation.     The final papers from first author, Dr. [Tang 00:06:08] and corresponding author Dr. [Fitzgerald 00:06:10] from the University of Pennsylvania Perlman School of Medicine in Philadelphia. These authors studied the cardiovascular consequences of prostanoid I-receptor deletion in microsomal prostaglandin E synthase-1 deficient hyperlipidemic mice. The clinical background to this research question is that inhibitors of cyclooxygenase-2 or Cox-2 are well-known to relieve pain, fever and inflammation by suppressing biosynthesis of prostacyclin and prostaglandin E2.     However, suppression of these prostaglandins particularly prostacyclin by Cox-2 inhibitors or deletion of the I-prostanoid receptor for prostacyclin is known to accelerate atherogenesis and enhance thrombogenesis in mice. In contrast, deletion of the microsomal prostaglandin E synthase1 has been shown to suppress PGE2 but increase biosynthesis of prostacyclin. It therefore confers analgesia while attenuating atherogenesis and does not predispose mice to thrombogenesis. Therefore, possibly contributing to cardiovascular efficacy.     In this particular study, therefore, the authors sought to determine the relative contribution of suppressing PGE2 versus augmenting prostacyclin to the impact of depletion of microsomal prostaglandin E synthase-1 in hyperlipidemic mice. The main findings were that augmentation of prostacyclin is the dominant contributor to the favorable thrombogenic profile of microsomal prostaglandin E synthase-1 depletion in these atherosclerotic mice while suppression of PGE2 accounted for the protective effects in atherosclerosis and the exciting clinical take-home message is that inhibitors of the microsomal prostaglandin E synthase-1 may be less likely to cause cardiovascular adverse effects than NSAIDS or specific inhibition of Cox-2. Those were the highlights of this week. Now for our feature paper.     Our feature paper today is entitled "The frequency, [type 00:08:41] and volume of leisure time physical activity and risk of coronary heart disease in young women" and I am so excited to be joined by two lovely ladies today to discuss this paper. First, the first and corresponding author Dr. Andrea [Comastick 00:08:58] from the School of Public Health of Indiana University Bloomington and Dr. Wendy Post, associate editor from the Johns Hopkins University. Welcome Andrea and Wendy.   Andrea: Hi. Thanks.   Wendy: Thank you so much for having us.   Carolyn: I am just so excited that we are talking about a paper about women being discussed by women. What more could you ask for? I have to say this is a first for Circulation on the Run, which is why I'm just so excited, so let's get straight into it.     Andrea, maybe I could just ask you to start by sharing the story of how you and your team came up with some new questions and new data because I'm sure a lot of listeners are thinking there's a lot of data on exercise and how good it is for cardiovascular health in women already.   Andrea: Yeah, that's a great question. When we started talking about conceptualizing this paper, the first thing was to focus on younger women. Most of the previous work on physical activity and heart disease has been in older adults and that's primarily because it's older adults that have heart attacks. It's hard to get a large enough study of young women that has enough coronary heart disease events to be able to study this. We were fortunate where we had a large cohort in the nurses health study too of women and because it's been followed for over 20 years, we had enough events to be able to examine this association.     We did want to think about, "Okay, what can we add?" because there's a lot of information about just overall physical activity and health, so what can we do differently? I'm pretty familiar with the physical activity guidelines and really tried to look at what in the guidelines currently and then what could we add? What could be of interest when they start revising the guidelines which is actually going to happen very soon.     That was when we started focusing on, "Okay, instead of looking at just overall activity, look at intensity, comparing moderate and vigorous." We also wanted to look at frequency of physical activity and looking at frequency but also adjusted for a total time or total amount of physical activity that somebody does. Then we are also, the third thing was that we thought was important was looking at adolescent physical activity.     We know that kids, unfortunately as they get older and get into their teenage years, their activity declines quite a bit. Looking at how this physical activity during adolescence earlier life impact coronary heart disease risk in adulthood. Those were the three main things that we were focusing on when we first conceptualized the paper.   Carolyn: Nice. Tell us, what did you find?   Andrea: We did find that exercise is just as beneficial in younger woman as it is in older adults, which is great. We also found that moderate intensity exercise is just as beneficial as vigorous intensity exercise, which I think is a really important message to get out there. I think a lot of people, especially those that are really inactive to begin with are completely intimidated about the fact of trying to think about going to a gym or trying to jog or run a marathon or something like that.     I think really emphasizing that moderate intensity activity is beneficial and we found that walking was actually the most beneficial activity that we looked at in our study, that brisk walking was really really good for everybody and really lowered risk of coronary heart disease.   Carolyn: Hooray.   Andrea: Yeah, and the other thing we found which might be of interest for those that are also extremely busy, especially this target population where a lot of people are moms and working was that frequency didn't seem to matter, that as long as people were exercising for a couple hours a week that they should be that they could accumulate it in a couple times a week or they could do it more frequently, four or five times a week. It didn't seem to matter.   Carolyn: That's cool. You know what? I think a lot of these things we'll also discuss at the Editorial Board when we're looking at this paper. Wendy, we promised that we would give a backstage pass to the Editorial Board and The Journal, so could you share a little bit about what we talked about there?   Wendy: Well, the Editorial Board was really excited about this paper. We loved the emphasis on young women and the important public health message about how we need to get out there and move and exercise to reduce our risk for cardiovascular disease. As was mentioned, there have been previous studies that also show the benefit of exercise but the Editorial Board especially liked the large sample size, the long duration of follow-up, the number of events that had been accrued that allowed for sophisticated analyses, adjustment for confounders and the very rigorous study design and excellent statistical methods that have been used in this study and so many other studies from the nurses health study, but I think we particularly just loved the message. The message was great.     We need to get out there and move. We need to tell our patients, especially young women, that now we have data that if you start exercising now, it will help in the future but also the study showed that if you hadn't exercised much in early life that's starting to exercise more proximal to the event was also important as well.   Carolyn: Thank you Wendy. I also remember that we talked about the lack of interaction with body mass index, and I thought that was a great message. Andrea, could you maybe share a little bit about that?   Andrea: Yeah, this is something that previous investigators have looked at the interaction between body mass index and exercise. Unfortunately, we've all found the same thing so it doesn't seem to matter whether women are normal weight or overweight or obese that they still get benefit when they exercise, and I think that's really encouraging. I know a lot of people might start to exercise because they really want to drop some weight but just trying to emphasize even if the numbers on the scale aren't changing, that exercise still has all these really great benefits for heart disease and also for many other diseases.   Carolyn: Exactly. Can I just ask both of you and maybe I'll start with Andrea, what will you do different now both as a woman and as a clinician seeing women now that you know what you do from your data?   Andrea: Well, I'm not a clinician. I'm an epidemiologist so unfortunately I don't get to see patients and counsel them although I do try to talk to community members as a public health person and really get in the community on board with what we're talking about. I just try to tell people, I actually talked to a group of people last week, and just trying to say, "Anything is better than nothing and just trying to even start with some short walks." Again, just emphasizing you don't have to go to a gym or you don't have to be doing anything that's super strenuous but just do stuff that feels good and just try to get your heart rate up a little bit like going out for a brisk walk. I think that's my main message that I try to tell everybody is at least start with something and get moving a little bit.   Carolyn: I love that. Wendy?   Wendy: I like to emphasize the data about brisk walking. I thought that was great because many of our patients don't want to join a gym, don't have the time to join a gym so just getting out and walking is fabulous exercise and now we have the data here that in young women that after 20 years of follow-up, brisk walking was associated with I think it was a 35% reduction in risk for cardiovascular disease during follow-up.     In addition, I liked the message about the total amount of time that you spend exercising in a week is what's important. It doesn't matter whether you divide that into seven days a week to get to that same amount of time or whether you do it in bursts of three days a week, and I think that's particularly important for the many women who have so many different responsibilities and may not have time every day to go out and exercise. The days that you do have time, just exercise a little bit more those days, so lots of really important messages for our patients and for ourselves.   Carolyn: I really couldn't agree more and just from my point of view, because I see a lot of patients in Asia and I do acknowledge just like you did, Andrea, in your paper that your data are predominantly in white populations. Still one of the messages I like to get out to the women I see is we have very skinny women and when I see younger women, and I really like emphasizing that, "Hey, just because you're not struggling with an obesity issue or just because you're young, it doesn't mean you don't need to exercise and that we all should just get moving." Thank you very, very much for that Andrea.   Andrea: Oh, no. It's my pleasure and thank you for having me come on today and talk about this.   Carolyn: Thank you too, Wendy. Do you have any other comments?   Wendy: No, but congratulations on your publication, Andrea.   Andrea: Oh, thank you so much, Wendy. I was really happy to get the message that guys were excited about it. Thank you so much.   Carolyn: You've been listening to Circulation on the Run. Thank you for joining us this week and please tune in next week.  

Caroline hosts the wondrous cultivated and cultivating Diana Beresford-Kroeger who embodies the assignment before us all of wedding science and myth, that our story-telling be irresistibly beguiling. Born into a notable family of Druid scholars, orphaned at an early age, schooled in Druid lore, multiple degrees in science, dedicated to Global Forests…http://www.stuartbernstein.com/dianaberesford-kroeger.html “Diana Beresford-Kroeger is a world recognized author and scientist with a unique background in both western science and the traditional ways of aboriginal peoples and the ancient world. Orphaned in Ireland in her youth, Beresford-Kroeger was educated by elders who instructed her in the Brehon knowledge of plants and nature. She went on to study classical botany and medical biochemistry and worked as a research scientist at Ottawa University and then at the Canadian Department of Agriculture Electron Microscopy Centre, where she discovered cathodoluminescence in biological materials. From 1973 to 1982, she conducted research at the University of Ottawa physiology department in conjunction with the Ottawa Heart Institute, specializing in hemodynamics. In the early 1980s, Beresford-Kroeger embarked on a significant change in her life's work. It began with an expansion of her private research garden and arboretum: Carrigliath. Having identified an absence in the scientific community of the ability to present science to the public and the urgent need to address the degradation of nature, she began her career in writing, broadcasting and lecturing. Flowing from her research and experience at Carrigliath, Beresford-Kroeger published over 200 articles in magazines, journals and newspapers in Canada, the United States and internationally. She also published five critically acclaimed books on nature and gardening. Her books include THE SWEETNESS OF A SIMPLE LIFE, THE GLOBAL FOREST, ARBORETUM BOREALIS: A LIFELINE OF THE PLANET, ARBORETUM AMERICA: A PHILOSOPHY OF THE FOREST, and A GARDEN FOR LIFE. She has served as a scientific advisor to a number of organizations, including the Irish Woodland League, Ecology Ottawa, Hidden Harvest of Ottawa, Canadian Organic Growers, Archangel Ancient Tree Archive and the Acadian Forest Research Centre and others. She has lectured widely across North America and Europe and has appeared on television and radio in Canada, the U.S., Europe and international short wave radio. For the last several decades, she has worked at Carrigliath, growing rare and endangered medicinal plants and trees. Beresford-Kroeger was inducted as a Wings Worldquest Fellow in 2010 and named one of Utne Reader's World Visionaries for 2011. In 2013, she was elected to the College of Fellows of the Royal Canadian Geographic Society. In 2016, CALL OF THE FOREST: THE FORGOTTEN WISDOM OF TREES, a feature film, television program and mobile app will be released. Please visit www.dianasjourney.com for more information. http://www.stuartbernstein.com/dianaberesford-kroeger.html The post The Visionary Activist Show – Caroline hosts the wondrous cultivated and cultivating Diana Beresford-Kroeger appeared first on KPFA.

Disciplinary technologies, Andrew graduated from Queen's University in 1974. Currently Chief of the Division of Prevention and Rehabilitation at the University of Ottawa Heart Institute, he is a Professor in the Faculty of Medicine at the University of Ottawa. In addition to his clinical responsibilities, Andrew has been extensively involved in sports and sport medicine for many years. Currently he is the President of the Commonwealth Games Association of Canada, has served as a physician at eight Olympic Games and has been the Team Physician for Canada's National Men's Basketball Team since 1978. A member of the Canadian Olympic Hall of Fame, Andrew served as Chair of the Canadian Centre for Ethics in Sport from its inception until 2003. Enhancing Sport Performance: Character, Culture, Coaching or Chemistry? Attempts to enhance sport performance have traditionally reflected an accentuation of skill, a burnishing of sport-specific tactics, and an augmentation of ‘fitness’. A contemporary challenge in sport is to distinguish those enhancement strategies which are seen as in keeping with established norms of sport practice, and those which are viewed as transgressing a standard of ‘appropriate sporting behaviour’. The programmes designed to curb performance-enhancing drug use are intended to address such a challenge. Sport is practiced in accordance with rules and norms that are ultimately arbitrary. Those vested with responsibility for the preservation of ‘fair play’ apply rules that can also be seen as arbitrary – their approaches represent an application, in part, of the “disciplinary technologies” – but which seek to ensure safety, fair-play and enduring public support of sport. Held, September 2011.