100 episodes

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

    • Life Sciences
    • 4.5 • 23 Ratings

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 October 20, 2020 Issue

    Circulation October 20, 2020 Issue

    This week's episode includes author Daniel Lackland and Associate Editor Mercedes Carnethon as they discuss the article "Forty-year Shifting Distribution of Systolic Blood Pressure with Population Hypertension Treatment and Control."
    TRANSCRIPT BELOW

    Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and it's editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.

    Dr Greg Hundley: And I'm Greg Hundley associate editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature is good news. What do I mean by good news? It's going to be a tale of how hypertension has evolved in the Southeastern United States. And it's going to review how that's progressed its treatment efficacy in both those of white, and men and women of black race. But before we get to that, how about we grab a cup of coffee and jump into some of the other articles in this issue.

    Dr Carolyn Lam: Man, you got my attention, Greg. You definitely got my attention.

    Dr Greg Hundley: Very good. Well, Carolyn, my first paper is from the world of basic science, and it's from Dr Maya Kumar from Stanford University School of Medicine. This group maps the step wise remodeling of pulmonary arteries in a robust chronic inflammatory mouse model of pulmonary hypertension. A model that demonstrates pathologic features of human disease, including right ventricular pressures, medial thickening, neointimal lesion formation, elastin breakdown, increased anastomosis within the bronchial circulation and perivascular inflammation, all of those combined. And the author sought to define the cell behaviors underlying each stage of vascular remodeling, and identified a pathway required for neointima formation with the premise being that this understanding could be pivotal in modulating progression of disease in pulmonary hypertension.

    Dr Carolyn Lam: Nice. So what did they find?

    Dr Greg Hundley: Well, Carolyn, they found surprisingly. The neointima arises from smooth muscle cells and not the endothelium. Medial smooth muscle cells proliferate broadly too thick in the media, after which a small number of smooth muscle cells are selected to establish the neointima. These neointimal founder cells subsequently undergo massive clonal expansion to form occlusive neointimal lesions. The normal pulmonary artery smooth muscle cell population is heterogeneous, and the authors identify a Notch3-marked minority subset of smooth muscle cells as the major neointimal cell of origin. Notch signaling is specifically required for the selection of neointimal founder cells, and Notch inhibition significantly improves pulmonary artery pressure in animals with pulmonary hypertension, thus perhaps providing a new mechanism from which to test therapies to thwart the progression of disease in those with pulmonary hypertension. Very interesting basic science work.

    Dr Carolyn Lam: Yeah. And very important too. Thanks Greg. Well, I've gotten another basic science paper too. First, let me ask you, do you think of DNA methylation much?

    Dr Greg Hundley: We hear a lot about that, Carolyn. Methylation and changing DNA and how it might be transcribed. Tell us more.

    Dr Carolyn Lam: DNA methylation is indeed a mechanism of gene transcription regulation. It's recently gained a lot of attention as a possible therapeutic target in cardiac hypertrophy and heart failure. However, its exact role in cardiomyocytes remains controversial. Thus, the authors Dr Stenzig from University Medical Center, Hamburg-Eppendorf and colleagues knocked out the main de novo DNA methyltransferase in cardiomyocytes. Also, called DNMT3A in human induced pluripotent stem cells. They then assess the functional consequences of DNA methylation deficien

    • 24 min
    Circulation October 13, 2020 Issue

    Circulation October 13, 2020 Issue

    This week’s episode includes author Mark Chan, editorialist Thomas Wang, and Associate Editor Wendy Post as they discuss the prioritization of candidates of post-myocardial infarction heart failure using plasma proteomics and single-cell transcriptomics.
    TRANSCRIPT BELOW:

    Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.

    Dr Greg Hundley: And I'm Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, really interesting, involving proteomics and single-cell transcriptomics, trying to identify how we could prioritize individuals after they've sustained myocardial infarction as to whether or not they'll develop heart failure. Lots to go over in that feature. But before we get to that, how about we grab a cup of coffee and start in with some of the other interesting papers in this issue?

    Dr Carolyn Lam: Absolutely. I've got my coffee and I have to tell you though, I am so excited about this feature, it comes from Singapore, but my first paper too is about transcriptomic profiling. But Greg, I have to ask you first, have you heard of the cardiac cellulome?

    Dr Greg Hundley: Oh my goodness, Carolyn. So you're starting the reverse-quiz strategy to help me. I have not heard of the cellulome. Help enlighten me.

    Dr Carolyn Lam: I just love that word. We've heard of all kinds of other omes, but this cellulome is something I've learned through today's paper. So the authors today who are Alexander Pinto from Baker Heart and Diabetes Institute and colleagues, they developed a novel cardiac single-cell transcriptomic strategy to characterize the cardiac cellulome. And that refers to the network of cells that forms the heart.
    The method was utilized to profile the cardiac cellular ecosystem in response to two weeks of angiotensin II as a pro-fibrotic stimulus. So what did they find? Well, they identified two previously undescribed cardiac fibroblasts populations that are the key drivers of fibrosis. Their names were Fibroblast-Cilp and Fibroblast-THBS4. Now, these do not correspond to smooth muscle actin-expressing myofibroblasts, which have been widely viewed as the primary drivers of fibrosis. So this is really novel. The cardiac cellular landscape was sexually dimorphic at the cell abundance and gene expression level, including cellular responses to angiotensin II induced tissue remodeling. So these data really provide insights into the cellular and molecular mechanisms that promote pathologic remodeling in the mammalian heart, and really highlight that early transcriptional changes precede chronic cardiac fibrosis.

    Dr Greg Hundley: Very nice, Carolyn. Well, let me switch to the clinical realm. And my first paper comes from Professor Holger Thiele from the Heart Center Leipzig at the University of Leipzig, and it's involving general versus local anesthesia with conscious sedation for patients undergoing TAVI procedures. So the study comes from the SOLVE-TAVI study, and it's a multi-center open-label 2x2 factorial randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVR, comparing conscious sedation versus general anesthesia. And the primary efficacy endpoint was powered for equivalence, and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatments, and acute kidney injury at 30 days.

    Dr Carolyn Lam: Wow, Greg, as I understand it, about half of patients today receive TAVI or TAVR with conscious sedation. So it's really an important question. So what did they find?
    Dr Greg Hundley: You're exactly right. So the composite end point occurred in 27% of the co

    • 23 min
    Circulation October 06, 2020 Issue

    Circulation October 06, 2020 Issue

    Dr James de Lemos: Hello, my name is James de Lemos. I'm the executive editor for Circulation, and I'm delighted to be joined here by Tim Gardner professor of surgery at University of Pennsylvania and our long-term associate editor in charge of cardiac surgical content at Circulation; and Marc Ruel, who is professor of cardiac surgery at University of Ottawa and the chair of the department there and who for many years has led the cardiac surgery supplement issue. Mark, Tim, welcome. Marc, please introduce this issue for our listeners.

    Dr Marc Ruel: Thanks so much, James. It's a very exciting year academically for cardiac surgery. We've had a lot of great developments from new data on long-term patency and outcomes with radial artery graphs through the results of the ischemia trial. And I think the 2020 themed issue around cardiovascular surgery is exactly in that framework. I think it will garner wide interest.
    It has a number of original papers, six original research articles, two more translational papers included in those six. We have two research letters. We have two frame of reference papers as well. And one state-of-the-art piece on exynos transplantation. We always keep in mind to have those issues very relevant to surgeons and to gather the very best cardiovascular surgery science. But in the same token we also want to make sure that they are relevant to the wider cardiovascular community. So I think, and I hope that everyone will enjoy this issue as the very best that's happened in cardiovascular surgery over the year.

    Dr James de Lemos: Well, thank you, Mark. Let's get started with discussion of the first paper and one that I'm actually quite excited about. This is long-term results of the radial artery CABG in clinical outcomes trials. What did the investigators look at in the study?

    Dr Marc Ruel: I think this is a very important paper, which adds to the increasing data around long-term benefits of arterial grafts, multi arterial grafts, and more specifically the radial artery. So here's a paper mostly from Australia. First author being Professor Buxton, who is a very well-known senior surgeon who has been really a grandfather in this field. And the last author is David Hare who is a cardiologist, also professor in Australia.
    And essentially there were two radial artery comparative trials that have been undertaken many years ago, well over a decade ago, when we now have 10-year data on those two trials. One of the trials compared the radial artery to the right internal thoracic artery. And the second trial a little bit smaller to the saphenous is vein grafts. So it holds 400 patients in the first randomized comparison and around 225 in the second, i.e. the radial versus saphenous vein.
    So it's wonderful that this is very long-term data. We have 10 year patency data, not on all patients. There was a distribution as to when the angiogram or the CT scan would be performed for patency over the course of the 10 years of the study. But the follow up is excellent and there are actually patency as well as clinical differences between the groups.
    And maybe I can say a couple of things around those. So, in the radial versus right internal thoracic artery cohort, there's both a patency and a mortality as well as a major adverse cardiac events benefit for the radial artery over the right internal thoracic artery. And yes, you've heard right, the comparator is the right internal thoracic artery.
    Now a couple of chatty it's all the Redis in there had to be done as a free graph. So they are connected. This is an art technique that everyone is very comfortable with and you have to use a six or seven Oh one friable internal thoracic ultra.
    So it may not really provide or present the call the way at its best advantage. If you will, there may be some benefits or a loss for not having it as a pedicle, but nevertheless,

    • 25 min
    Circulation September 29, 2020 Issue

    Circulation September 29, 2020 Issue

    This week’s episode includes author Finnian Mc Causland and Associate Editor Justin Ezekowitz as they discuss angiotensin-neprilysin inhibition and renal outcomes in 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. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.
    Dr Greg Hundley: And I'm Greg Hundley Associate Editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia.
    Dr Carolyn Lam: Greg, we're going to be talking about RNEs and renal outcomes in HFpEF. Oh, you got to hold me back this is going to be such an interesting discussion. But maybe let's grab our coffees. Are you ready to talk about some of the papers in today's issue?
    Dr Greg Hundley: You bet.
    Dr Carolyn Lam: Well the first paper I have really represents a novel gene therapy approach to atrial fibrillation. So doctors led by Dr Arora from Northwestern University Feinberg School of Medicine and colleagues used a novel gene therapy approach in a canine rapid atrial pacing model of atrial fibrillation to demonstrate that NADPH oxidase-2 or NOX2 generated oxidative injury by causing upregulation of a constitutively active form of acetylcholine-dependent potassium current, or IKH is an important mechanism underlying electrical remodeling in the fibrillating atrium.
    Dr Greg Hundley: Wow, Carolyn, very interesting. Tell us a little bit more about this gene therapy approach.
    Dr Carolyn Lam: They performed targeted expression of anti-NOX2 short hairpin RNA in the intact atria of the dogs, and then subjected those animals to rapid atrial pacing for a period of several weeks to months. The novel atrial gene therapy approach prevented the development of electrical remodeling and sustained atrial fibrillation thus demonstrating for the first time a clearer causative role for NOX2 generated oxidative injury in the creation, as well as the maintenance of electrical remodeling in atrial fibrillation. Furthermore, they demonstrate that a likely cellular and molecular mechanism by which oxidative injury created a vulnerable substrate for atrial fibrillation, the results of this study yield therefore valuable mechanistic insights into the pathogenesis of atrial fibrillation and have important therapeutic implications for this clinical management.
    Dr Greg Hundley: Very nice, Carolyn. We need more therapies for AFib. Boy, that's so informative. Well, the next paper that I have sort of merges the world of electrophysiology with the world of imaging and it comes to us from Dr Michela Casella from Centro Cardiologico Monzino. Among 162 consecutive patients, this study evaluated the combined utility of electroanatomic voltage mapping coupled with cardiovascular magnetic resonance imaging to guide endomyocardial biopsies.
    Dr Carolyn Lam: Oh, so interesting. A combined noninvasive and invasive electrical guide to perform cardiac biopsies, wow. So what did they find Greg?
    Dr Greg Hundley: So they found that the sensitivity of pooled electroanatomic voltage mapping and cardiovascular magnetic resonance was as high as 95%. EVM and CMR together conferred an endomyocardial biopsy positive predictive value of 89%. Endomyocardial biopsy analysis allowed to reach a new diagnosis different from the suspected diagnosis in 39% of patients, complication rates were low, mostly vascular access related, with no patients requiring urgent management. Most impressive for this manuscript are the illustrative figures that are provided. It's really a great article for those performing biopsies, doing imaging, or the EP procedures that guide the biopsy process.
    Dr Carolyn Lam: Really nice, Greg, thanks. Now for the last paper, have you ever thought about atherosclerosis

    • 19 min
    Circulation September 22, 2020 Issue

    Circulation September 22, 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 at VCU Health in Richmond, Virginia.
    Dr Carolyn Lam: Greg, our feature paper today talks about the risks of sudden cardiac death, something that we still grapple with, and do you know what, really highlights the important emerging role of biomarkers of myocardial stress, myocardial injury, or even subclinical inflammation in predicting this risk. A really important discussion coming right up.
    But before we do that, let me tell you about a paper in today's issue that really provides novel mechanistic insights into atrial fibrillation pathogenesis. In fact, this is the first paper to demonstrate that decreased expression of a striated muscle preferentially expressed protein kinase, or SPEG in atria, is causally linked to altered diastolic calcium handling and human paroxysmal atrial fibrillation.
    This is from corresponding author, Dr Wehrens and colleagues from Baylor College of Medicine. And they used phosphoproteomic studies to identify S2367 on ryanodine receptor type-2 as a novel kinase substrate of SPEG. Through the study of novel ryanodine receptor type-2 phospho-mutant mouse models, they revealed that in contrast to previously characterized phosphorylation sites on this receptor, S2367 phosphorylation inhibited diastolic calcium release from the receptor, while loss of phosphorylation of the site increased atrial fibrillation susceptibility.
    Dr Greg Hundley: Wow, Carolyn. So the clinical implication is that normalizing S2367 phosphorylation in SPEG activity may provide novel therapeutic opportunities for the treatment of atrial fibrillation, right?
    Dr Carolyn Lam: You bet, Greg. Too smart. And this is discussed in an accompanying editorial by Drs Knollmann and Blackwell from Vanderbilt University Medical Center.
    Dr Greg Hundley: Very nice, Carolyn. Well, I've got a paper pertaining to COVID-19, and it comes to us from Dr Leo Nicolai from the Klinik der Universität München in Germany. Carolyn, I really enjoyed this article about COVID-19. I found it very intriguing, and the study addresses the mechanisms by which the SARS-CoV-2 infection, associated pneumonia or COVID-19, leads to subsequent respiratory failure, complicating renal and myocardial involvement, and the prothrombotic phenotype found in some patients with COVID-19.
    62 subjects were included in the study, 38 patients with RT-PCR confirmed COVID-19 and 24 non-COVID-19 controls. The investigative team performed histopathological assessments of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet-neutrophil functions and coagulation tests.
    Dr Carolyn Lam: Wow, that sounds like really sort of in-depth testing. And what did they find?
    Dr Greg Hundley: Several things, Carolyn. First, the authors found evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. They found that in COVID-19 patients, inflammatory microvascular thrombi are present in the lung, kidney and heart, containing neutrophil extracellular traps associated with platelets and fibrin.
    Second, they observed that COVID-19 patients also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood which changes with disease severity, whereas cases of intermediate severity show an exhausted platelet and hyperreactive neutrophil phenotype. This finding differs for severely affected individuals. Among severely affected COVID-19 patients, there is excessive platelet and neutrophil activation compared to healthy c

    • 28 min
    Circulation September 15, 2020 Issue

    Circulation September 15, 2020 Issue

    This week’s episode includes author Jeffrey Testani and Associate Editor Justin Grodin as they discuss empagliflozin heart failure, including diuretic and cardio-renal effects.
    TRANSCRIPT:
    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 Centre and Duke National University of Singapore.
    Dr Greg Hundley: And I'm Greg. I'm the director of the Pauley Heart Center at VCU Health in Richmond, Virginia.
    Dr Carolyn Lam: Greg, the SGLT-2 inhibitors have really revolutionized heart failure treatment, but we still need to understand a bit better how they work. And today's feature paper is so important, talking about diuretic and cardio-renal effects of Empagliflozin. That's all I'm going to tell you though, because I want to talk about another paper in the issue very related. And it's from John McMurray from the University of Glasgow with insights from DAPA-HF. But maybe a question for you first. Have you ever wondered what to do about loop diuretics doses in patients with heart failure and whom you're thinking of initiating an SGLT-2 inhibitor, Greg?
    Dr Greg Hundley: Absolutely, Carolyn. That comes up all the time and how do you make that transition.
    Dr Carolyn Lam: Exactly. And so this paper is just so important, and Dr McMurray and his colleagues showed that in the DAPA-HF trial, the SGLT-2 inhibitor, dapagliflozin, first, just as a reminder, reduce the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. And in the current paper, they examined the efficacy and tolerability that dapagliflozin falls in relation to background diuretic treatment and change in diuretic therapy, following randomization to dapagliflozin or placebo. They found that 84% of patients randomized were treated with a conventional diuretic, such as the loop or thiazides diuretic. The majority of patients did not change their diuretic dose throughout follow-up. And the mean diuretic dose did not differ between the dapagliflozin and placebo group after randomization. Although a decrease in diuretic dose was more frequent with dapagliflozin than with placebo, the between-group differences were small. So treatment with dapagliflozin is safe and effective regardless of diuretic dose or diuretic use.
    Dr Greg Hundley: Very nice, Carolyn. That's such a nice practical article. I really enjoyed your presentation of that. My next article comes from Professor Karlheinz Peter, and it's investigating the reduction of shear stress and how that might impact monocyte activation in patients that undergo TAVI. So this group hypothesized that the large shear forces exerted on circulating cells, particularly in the largest circulating cells, monocytes, while passing through stenotic aortic valves results in pro-inflammatory effects that could be resolved with TAVI. So to address this, the investigative team implemented functional essays, calcium imaging, RNA gene silencing and pharmacologic agonist and antagonist to identify the key mechanical- receptor mediating the shear stress sensitivity of the monocytes. In addition, they stained for monocytes in explanted, stenotic, aortic human valves.
    Dr Carolyn Lam: Lots of work done in a very translational study. So what did they find Greg?
    Dr Greg Hundley: They found monocyte accumulation at the aortic side of the leaflets in the explanted aortic valves. That was the human subject study. In addition, they demonstrated that high shear stress activates multiple monocyte functions and identify PZ1 as the main responsible mechanoreceptors representing, therefore, a potentially druggable target. So reducing the shear stress from a stenotic valve promotes an anti-inflammatory effect and, therefore, could serve as a novel therapeutic benefit of th

    • 27 min

Customer Reviews

4.5 out of 5
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23 Ratings

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mcgui007

awesome; informative; efficient. Capsule summaries of the original research and engaging interview with selected authors and editors.

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Useful CV Podcast

Great summary of the Circulation issues. Best part is the interview portion which features authors and editors.

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Engaging

Excellent, concise summary of the latest research. Love the in depth discussion of the featured article. Amazingly engaging for a science podcast!

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