100 episodios

Each 15-minute podcast begins with an overview of the issue’s contents and main take-home messages for busy clinicians on the run. This is followed by a deep dive into a featured article of particular clinical significance: views will be heard from both author and editor teams for a “behind the scenes” look at the publication. Expect a fun, highly conversational and clinically-focused session each week!

Circulation on the Run Carolyn Lam, MBBS, PhD

    • Ciencias de la vida

Each 15-minute podcast begins with an overview of the issue’s contents and main take-home messages for busy clinicians on the run. This is followed by a deep dive into a featured article of particular clinical significance: views will be heard from both author and editor teams for a “behind the scenes” look at the publication. Expect a fun, highly conversational and clinically-focused session each week!

    Circulation August 11, 2020 Issue

    Circulation August 11, 2020 Issue

    Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.
    Dr Greg Hundley: And I'm Dr Greg Hundley, associate editor, director of the Pauley Heart Center, VCU Health in Richmond, Virginia.
    Dr Carolyn Lam: Greg, guess what we're discussing for the feature discussion? We're talking about sugar sweetened beverage tax. Isn't that interesting? We talk about sugar sweetened beverages and their health impacts, but don't actually look at how tax policies may impact cardiovascular outcomes. So this paper is super interesting, can't wait to get to it, but I really want to get my cup of coffee and discuss a couple of other really cool stuff in today's issue. I'm going to start. Do you think about factor V Leiden much?
    Dr Greg Hundley: Carolyn, we are early in August and we have all new house officers rotating, and actually we do discuss factor V Leiden, and we think about Protein C and Protein S deficiencies, et cetera. But how about if you tell us about your paper and educate us a little bit more on the topic?
    Dr Carolyn Lam: Okay. So first of all, it's Leiden or Leiden, I'm not sure. So I'm going to go with your pronunciation. Factor V Leiden is a genetic variant leading to alteration of the inactivation site of factor V, which in turn leads to activate a Protein C resistance and a prothrombotic state, just like you said, Greg. Affecting almost 5% of the Caucasian population, carriers of a factor V Leiden mutation have a fourfold higher risk of venous thromboembolism. However, the risk of arterial atherothrombotic events, such as myocardial infarction or stroke, conferred by the presence of this variant is less certain. So Dr Patel from University College London, and Dr Asselbergs from University Medical Center Utrecht and colleagues assess the association of the factor V Leiden polymorphism with subsequent atherothrombotic events, including mortality in individuals with established coronary heart disease using an individual level data meta-analysis of 25 prospective studies from the genetics of subsequent or GENIUS coronary heart disease consortium.
    Dr Greg Hundley: Well Carolyn, what did they find?
    Dr Carolyn Lam: In nearly 70,000 patients with established coronary heart disease, factor V Leiden was not associated with an increased risk of further atherothrombotic events or death compared to non-carriers. A post hoc analysis, however, suggested that factor V Leiden carriers with established coronary heart disease may gain greater protection from subsequent coronary heart disease, death, or myocardial infarction from dual antiplatelet therapy compared to non-carriers. The routine assessment of factor V Leiden genotype to improve risk stratification in secondary prevention settings is therefore unlikely to be of value and is not recommended. However, further work is required to understand if there may instead be a pharmacogenomic role for factor V Leiden status to help personalize treatment with intensive antiplatelet therapy.
    Dr Greg Hundley: Very nice, Carolyn. Well, my next paper is from Dr Michelle O'Donoghue from Brigham and Women's Hospital, and creates an interesting question for you, Carolyn. Would you be comfortable discontinuing aspirin three months after PCI in lieu of continuing a P2Y12 inhibitor?
    Dr Carolyn Lam: Ah, big, big question. Not until guidelines change, but tell me, tell me, tell me, Greg, what this paper said.
    Dr Greg Hundley: Well, before we get some of these more randomized trial, this study included a meta-analysis of 32,145 patients, 14,095, or 43%, with stable coronary artery disease and 18,000, nearly 56%, with ACS from randomized trials during the time period of 2001 to 2020. And they had to study discontinuing aspi

    • 24 min
    Circulation August 4, 2020 Issue

    Circulation August 4, 2020 Issue

    Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.
    Dr Greg Hundley: And I'm Dr Greg Hundley from VCU Health, the Pauley Heart Center in Richmond, Virginia.
    Dr Carolyn Lam: Our feature paper today is very important and pertinent to the times, talking about the multi-system inflammatory syndrome in children in our current global SARS coronavirus 2 pandemic. Really, really important stuff, but you have to hold on, listen with us to this summary which is full of really exciting papers. You know what, Greg? I'm going to start. So what do you know about the rostral medial prefrontal cortex of our brains?
    Dr Greg Hundley: Well, let's see. I wonder if it has anything to do with emotion or stress maybe?
    Dr Carolyn Lam: Oh, you're too smart. Either that or that coffee is loaded. Very good answer. The rostral medial prefrontal cortex is an important brain region that processes stress and regulates immune and autonomic functions. Now, since psychological stress is a risk factor for major adverse cardiovascular events in individuals with coronary artery disease, our authors today, Dr Shah and colleagues from Rollins School of Public Health, Emory University, hypothesize that changes in the rostral medial prefrontal cortex activity with emotional stress may be informative for future risk of MACE or major adverse cardiovascular events. They examined 148 participants with stable coronary artery disease who underwent acute mental stress testing using a series of standardized speech or arithmetic stressors and simultaneous brain imaging with high resolution positron emission tomography brain imaging. They defined high rostral medial prefrontal cortex activation as a difference between stress and control scans greater than the median value for the entire cohort. They also measured interleukin-6 levels 90 minutes post stress and high frequency heart rate variability during stress.
    Dr Greg Hundley: Wow, Carolyn, what an intriguing article correlating the imaging findings with stress and systemic inflammation. What did they find?
    Dr Carolyn Lam: So they found that higher roster medial prefrontal cortex activity with mental stress was independently associated with higher risk of major adverse cardiovascular events. Immune and autonomic responses to mental stress contributed to the increased of adverse events among those with the higher stress reactivity. Stress-induced activation may therefore represent a new method of risk stratification of individuals with coronary artery disease.
    Dr Greg Hundley: Very nice. That really ties a lot together. Makes a lot of sense, Carolyn. Well, my first paper is from Dr Patrick Ellinor from Massachusetts General Hospital and the Harvard Medical School, but first Carolyn a quiz. So here's the background to the quiz. I'm going to talk about the heart myocytes versus the fibroblast versus the microcirculatory cells. So within each of those groups, Carolyn, this is a way or no way, are all the cell types the same?
    Dr Carolyn Lam: Well, at embryonic stage maybe? All right, I'll be superficial about it. No way, they're different.
    Dr Greg Hundley: Very good, Carolyn. These authors applied recent advances in low input RNA sequencing that allowed definitions of cellular transcriptome to assess the cellular and transcriptional diversity of the non-failing human heart.
    Dr Carolyn Lam: Wow. What did they find?
    Dr Greg Hundley: Carolyn, the author sequences the transcriptomes of 287,269 single cardiac nuclei, revealing a total of nine major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses included two distinct groups of resident macrophages, four endothelial subtypes, and two fibroblast subs

    • 21 min
    Circulation July 28, 2020 Issue

    Circulation July 28, 2020 Issue

    Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.
    Dr Greg Hundley: And I'm Dr Greg Hundley, associate editor, Director of the Pauley Heart Center from VCU Health in Richmond, Virginia.
    Dr Carolyn Lam: Our feature paper today discusses trans-ethnic genome-wide association studies and the insights in the genetic architecture and heritability of long QT syndrome, a massive study that we will be digging into, but only after we talk a little bit about the other papers in this week's issue. And I'm going to start, Greg. Are you ready with your coffee?
    Dr Greg Hundley: I am.
    Dr Carolyn Lam: The first original paper really represents seminal work, showing that the endothelium can directly regulate obesity and insulin resistance. Now, as obesity develops, there is a decline in adipose tissue vascularity, which seems counterintuitive, and an increase in fibrosis.
    So authors, led by Dr Chen from the Irell and Manella Graduate School of Biological Sciences in the City of Hope, speculated that the reduction in vascularity in this adipose tissue might have an adverse effect on adipose tissue function. Now, these authors previously identified Argonaute-1, or AG01, a key component of microRNA-induced silencing complex, as a crucial regulator in hypoxia-induced angiogenesis.
    So in the current study, they aim to determine the AG01-mediated endothelial cell transcriptome, the functional importance of AG01-regulated endothelial function in vivo, and the relevance to adipose tissue function and obesity.
    A new mouse model with genetic deletion of AG01 in the endothelium was useful to investigate the importance of endothelial regulation of adipose tissue function. The findings were that in mice fed high fat, high sucrose diet, the suppression of endothelial AG01 promoted adipose tissue browning, and led to an anti-obesity phenotype. Endothelial cell AG01 thrombospondin-1 pathway was induced in the endothelium from human donors with insulin resistance.
    In total, this study suggests a novel mechanism, by which endothelial cells through AG01 thrombospondin-1 pathway controls vascularization and function of adipose tissues, insulin sensitivity, and whole-body metabolic state.
    Dr Greg Hundley: Interesting, Carolyn. So tell me about this clinically. Where do we take this from here?
    Dr Carolyn Lam: I thought you would ask. So endothelial dysfunction, per se, can cause metabolic dysregulation, rendering targeting dysfunctional endothelium, a potential therapeutic strategy to counteract obesity, and metabolic disorders. So this study really opens a door to that.
    Dr Greg Hundley: Very nice. Well, I've got another basic science paper, and it evaluates single-cell RNA sequencing to dissect the immunological network of autoimmune myocarditis. And it comes from Dr Jiangping Song from the State Key Laboratory of Cardiovascular Disease of Fuwai Hospital, and the National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, and Peking Union Medical College.
    So Carolyn, the study aimed to investigate the immunological network during the transition from myocarditis to cardiomyopathy, and to identify the genes contributing to the inflammatory response to myocarditis.
    So mice were treated with myosin heavy chain alpha-peptides to generate an experimental autoimmune myocarditis model. The investigators performed single-cell RNA sequencing analysis of CD45 plus cells extracted from mouse hearts during different experimental autoimmune myocarditis phases, including normal control, acute inflammation, subacute inflammation, and then in the myopathy phase. Also, human heart tissues were collected from surgically removed hearts of patients who had undergon

    • 22 min
    Circulation July 21, 2020 Issue

    Circulation July 21, 2020 Issue

    This week’s episode of Circulation on the Run features author Robert Yeh and Associate Editor Brendan Everett as they discuss the article "Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement: Findings from the EXTEND Study."
    TRANSCRIPT
    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.
    Greg Hundley: And I'm Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn this week, we're going to examine outcomes in patients that have undergone transcatheter aortic valve replacement or TAVR. I can't wait to get to the results from the EXTEND study. But before we do that, how about we grab a cup of coffee and start in with some of the papers and maybe I'll go first this time.
    My paper involves a validated model for sudden cardiac death risk prediction in pediatric hypertrophic cardiomyopathy. And the corresponding author is Dr Seema Mital from the Hospital for Sick Children. Well, Carolyn in this study, the objective was to develop and validate a sudden cardiac death risk prediction model in pediatric hypertrophic cardiomyopathy to guide sudden cardiac death prevention strategies.
    To address this, the authors performed an international multi-center observational cohort analysis. Phenotype positive patients with isolated hypertrophic cardiomyopathy, who were under the age of 18 years at diagnosis were eligible. The primary outcome variable was the time from diagnosis to a composite of sudden cardiac death events at five years of follow-up. That included sudden cardiac death, resuscitated sudden cardiac arrest, and aborted sudden cardiac death, that is, an appropriate shock following primary prevention ICD.
    Carolyn Lam: Nice. What did they find?
    Greg Hundley:   Well, overall 572 patients met the eligibility criteria with 2,855 patient years of follow-up. The five-year cumulative proportion of sudden cardiac death events was 9%. Risk predictors included age at diagnosis, documented non-sustained ventricular tachycardia, unexplained syncope, septal diameter Z scores, LV posterior wall diameter Z scores, LA diameter Z scores, peak LV outflow tract gradients, and the presence of a pathogenic variant.
    Now, unlike adults, LV outflow tract gradient had an inverse association and family history of sudden cardiac death had no association with sudden cardiac death. The combination of clinical and genetic data were developed to predict five-year freedom from sudden cardiac death.
    In conclusion, the authors study provides a validated sudden cardiac death risk prediction model with over 70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. These results therefore raise the possibility that an individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for these children prior to an ICD insertion.
    Carolyn Lam: Very interesting. Well, Greg, have you ever wondered what are the temporal trends in the burden of comorbidities and risk of mortality among patients with heart failure with preserved ejection fraction or HFpEF and heart failure with reduced ejection fraction or HFrEF? Well, the next paper comes from Dr Caughey and colleagues from University of North Carolina and North Carolina State University who performed an analysis of the community surveillance component of the atherosclerosis risk in communities, or ARIC study, and they found a significant increase in the burden of comorbidities among hospitalized patients with HFpEF as well as HFrEF across both sexes. Hig

    • 25 min
    Circulation July 14, 2020 Issue

    Circulation July 14, 2020 Issue

    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 in Duke National University of Singapore.
    Dr Greg Hundley: I'm Greg Hundley, associated editor from the VCU Pauley Heart Center in Richmond, Virginia.
    Dr Carolyn Lam: Greg, today's speaker paper is really special on a number of levels. First, it's a research letter and secondly, it's actually basic science. Now, this tells you it's got to be really special. Well, I'll just give you a hint. It talks about a new therapy for stroke. I'm going to leave it at that, leave you guessing because you've got to hang on as we tell you about the rest of the issue and then listen to the feature discussion. Now, the first original paper here, I want to describe as a basic paper focusing on PDE4B in heart failure.
    Dr Greg Hundley: All right, Carolyn, I'm not even going to let you start to quiz me on this. Can you tell me what in the world is PDE4B?
    Dr Carolyn Lam: All right. Phosphodiesterases, or PDEs, really represent a highly diverse super family of enzymes among which PDE3 and PDE4 are the main phosphodiesterases that degrading cyclic AMP with a high affinity in the heart. The cyclic AMP hydrolyzing phosphodiesterase 4B, which is PDE4B, is the key negative regulator of cardiac beta-adrenergic receptor stimulation. PDE4B deficiency leads to abnormal calcium handling and PDE4B is decreased in pressure overload hypertrophy suggesting that increasing PDE4B in the heart may be beneficial in heart failure. These authors led by Dr Vandecasteele from Inserm tested this hypothesis in elegant experiments involving both human cardiac tissues and transgenic mouse lines.
    Dr Greg Hundley: Carolyn, that was just a wonderful explanation and I really learned about these phosphodiesterases. Now, tell me what did they find in their study?
    Dr Carolyn Lam: The cyclic AMP hydrolyzing enzyme, PDE4B, was decreased in human failing hearts. Cardiac over expression of PDE4B in mice, resulting in a 15-fold increase in cyclic AMP hydrolysis decreased cardiac contraction and protected against the cardiotoxic effects of chronic beta-adrenergic stimulation. Whereas transgenic mice with a 50-fold increase in cardiac cyclic AMP hydrolysis underwent maladaptive remodeling. Furthermore, cardiac PDE4B gene transfer with serotype nine adeno associated viruses resulted in a significantly lower increase in cardiac PDE4B and protected against chronic catecholamine stimulation and transaortic constriction without depressing basal cardiac function. These results overall suggest that a moderate increase in cardiac PDE4B is beneficial to counteract the detrimental effects of excessive sympathetic system activation in heart failure and increase in PDE4B in the human heart could be achieved by gene therapy with adeno associated viruses or by using recently developed small molecules with PDE4 activating properties.
    Dr Greg Hundley: Wow, Carolyn. Very interesting. I mean, perhaps this'll work its way into heart failure management. Well, my study, our first study to describe involves the comparative efficacy and safety of oral P2Y12 inhibitors and acute coronary syndromes. It's a meta-analysis of 52,816 patients from 12 randomized trials. It comes to us from Professor Eliano Navarese from Nicholas Copernicus University. All right, Carolyn, here's your quiz. Have you wondered which PGY inhibitor is optimal for reducing risk of adverse cardiovascular events?
    Dr Carolyn Lam: Oh, that's an easy one. Of course I've wondered, but you're going to tell us the results.
    Dr Greg Hundley: It's getting harder and harder to trip you up Carolyn. Very clever, okay. This study aims to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor and clopidogrel in acute

    • 25 min
    Circulation July 7, 2020 Issue

    Circulation July 7, 2020 Issue

    Dr Carolyn Lam: Well, the 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.
    Dr Greg Hundley: And I'm Dr Greg Hundley, associate editor from the Pauley Heart Center at VCU Health in Richmond, Virginia.
    Well, Carolyn, this week's feature involves the Compass trial, and we'll be talking about a comparison of low-dose rivaroxaban plus aspirin compared to aspirin alone in patients with chronic vascular disease. But before we get to that, how about if we break away and discuss a few other papers. And I'll go first this time, because this week we're going to introduce another new feature in addition to Carolyn's Quiz.
    Dr Carolyn Lam: Wait a minute. This was not on the script. What's going on, Greg?
    Dr Greg Hundley: It's on the script!
    Carolyn, let me get to my first paper. It's from Professor Junling Liu from Shanghai Jiao Tong University School of Medicine, and it involves branched-chain amino acid catabolism and how that may promote thrombosis risk by enhancing tropomodulin-3 propionylation in platelets.
    But first, we've got a new feature to add to Carolyn's Quiz. It's called Way or No Way.
    Dr Carolyn Lam: Just so everybody knows. This was a one-way decision to add this new component of Carolyn's Quiz, but okay, I'm all for it. Go, Greg!
    Dr Greg Hundley: Okay. All right. It's a fast, quick question where our listeners seek your guidance regarding an important scientific discovery from one of our published manuscripts. Are you ready?
    Dr Carolyn Lam: No.
    Dr Greg Hundley: Okay. Here's your question. Do branched-chain amino acids promote arterial thrombosis. Way or no way?
    Dr Carolyn Lam: Maybe?
    Dr Greg Hundley: Okay, Carolyn.
    Dr Carolyn Lam: I have a feeling you're going to tell us yes, although I wouldn't have guessed that straight away.
    Dr Greg Hundley: Okay. Remember that branched-chain amino acids are essential nutrients, including leucine, isoleucine, and valine, and they serve as a resource for energy production and the regulator of important nutrient and metabolic signals.
    In this study, the activity of human platelets from healthy subjects before and after ingestion of branched-chain amino acids were measured. PP2Cm-deficient mice were used to elucidate the impacts of BCAA catabolism on platelet activation and thrombus formation.
    Dr Carolyn Lam: Now okay, okay. So what did they find? Way or no way?
    Dr Greg Hundley: Ingestion of branched-chain amino acids significantly enhanced the activity of platelets in response to agonists and increased the risk of arterial thrombosis. The branched-chain amino acid catabolic pathway-driven propionylation of tropomodulin-3 at K255 was found to be an important mechanism underlying the branched-chain amino acid-facilitated platelet activation, and elevated levels of branched-chain amino acids and enhanced expression of positive regulators of branched-chain amino acid catabolism in platelets were found probably responsible for the high platelet activity in type 2 diabetes mellitus.
    Dr Carolyn Lam: Very interesting. So yes, it is possible. And what is the clinical implications?
    Dr Greg Hundley: Right, Carolyn. Branched-chain amino acids, or their catabolites, enhance the risk of arterial thrombosis in small animals, and perhaps future human subject studies, that restrict branched-chain amino acid intake or target branched-chain amino acid catabolism may serve as a novel strategy for anti-thrombosis therapy.
    Dr Carolyn Lam: Interesting. Okay, Greg. Here you go. Question for me. Have you heard of Home Time?
     
    Dr Greg Hundley: Home Time? Yes. Home Time. It's not like time out for our kids, but we've been having a lot of Home Time in this COVID-19 with our families.
    Dr Carolyn Lam: All right. Touché. Touché. Hom

    • 23 min

Top podcasts en Ciencias de la vida

Otros usuarios también se han suscrito a