Circulation October 5, 2021 Issue

10/04/21 • 30 min

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...

Dr. James de Lemos:

Dr. Marc Ruel:

Dr. James de Lemos:

Dr. Marc Ruel:

Dr. Michael Fischbein:

Yeah. Thanks, Marc. I think that...

Previous Episode

Circulation September 28, 2021 Issue

This week's episode features a panel discussion. Please join author Harmony Reynolds, editorialist David Newby, and Associate Editors Nicholas Mills and Sandeep Das as they discuss the articles "Natural History of Patients with Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study, "Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity," and editorial "Forget ischemia, it's all about the plaque."

Dr. Greg Hundley:

Welcome listeners to this week's, September 28th, issue of Circulation on the Run. And I'm Dr. Greg Hundley, Director of the Poly Heart Center at VCU Health in Richmond, Virginia, and associate editor at Circulation. And this week, listeners, we have an outstanding feature discussion. It's actually forum where we're going to discuss from Dr. Reynolds two papers pertaining to the ischemia trial. One looking really at the functional importance of stress testing, the other looking at the anatomical importance of cardiac CT scanning. We're going to have two of the associate editors along with Dr. Reynolds, each that handled the two papers and also a guest editorialist that will help put the entire paper together. Well, before we get to that, we're going to start and review some of the other papers in this issue. And let's grab a cup of coffee and get started.

Dr. Greg Hundley:

The first comes to us from Dr. Maliheh Nazari-Jahantigh from Ludwig Maximilian University in Munich, Germany, and it pertains to atherosclerotic plaque rupture. So the necrotic core of an atherosclerotic plaque is partly formed by ineffective efferocytosis, which increases the risk of an atherosclerotic plaque rupture. And in cell biology, efferocytosis comes from the Latin word effero, which means to take to the grave or to bury. And it's really the process by which apoptotic cells are removed by phagocytic cells. And so therefore, it can be regarded as the burying of "dead cells." Now MicroRNAs contribute to necrotic core formation by regulating efferocytosis as well as macrophage apoptosis. We also know that atherosclerotic plaque rupture occurs at an increased frequency in the early morning, indicating that diurnal changes occur in plaque vulnerability. Now all those circadian rhythms play a role in atherosclerosis, the molecular clock output pathways that control plaque composition and rupture susceptibility are unclear.

Dr. Greg Hundley:

And so these authors investigated this phenomenon. And what they found, interestingly, their results suggest that the molecular clock in atherosclerotic lesions induces a diurnal rhythm of apoptosis regulated by circadian Mer 21 expression in macrophages that is not matched by efferocytosis, and thereby increasing the size of the necrotic core of these plaques. So clinically, the implications are that a macrophage death clock controlled by mer 21 may enhance lesion growth and susceptibility to plaque rupture indicating that the molecular clock can have detrimental effects under pathologic conditions. And additionally, the molecular clock in lesional macrophages may contribute to the circadian pattern of myocardial infarction, which could be a target for preventive measures to limit the mismatch between apoptosis and efferocytosis and thus reduce plaque vulnerability in the early morning.

Dr. Greg Hundley:

Well, our second paper comes to us also from the world of preclinical science, and it's from Professor Thomas Braun from the Max Planck Institute for heart and lung research. And this particular paper pertains to pulmonary hypertension. And as we know, pulmonary hypertension and chronic obstructive pulmonary disease, or COPD, originate from a complex interplay of environmental factors in genetic predispositions and little is known about developmental abnormalities or epigenetic dysregulation that might predisposed individuals to develop pulmonary hypertension or COPD in adults. So these authors screen a cohort of human pulmonary hypertension in COPD patients for changes of histone modifications by immunofluorescent staining. And also, they developed knockout mouse lines targeting cardiopulmonary progenitor cells and different heart and lung cell types.

Dr. Greg Hundley:

Now molecular, cellular and biochemical techniques were applied to analyze the function of SUV420H1-dependent epigenetic processes in cardiopulmonary progenitor cells and their derivatives. Well, what did they find? So the investigators found that loss of SUV420H1 in cardiopulmonary progenitor cells caused a COPD-like pulmonary hypertension phenotype in mice, including formation of perivascular tertiary lymphoid tissue, and goblet cell hyperplasia, hyperproliferation of smooth muscle cells and myofibroblast, impaired alveolarization and maturation of defects of the microvasculature leading to massive ripe ventricular dilation and premature death.

Dr. Greg Hundley:

Now mechanisti...

Next Episode

Circulation October 12, 2021 Issue

Please join author Milton Packer and Associate Editor Justin Ezekowitz as they discuss the Perspective "Heart Failure and a Preserved Ejection Fraction: A Side-by-Side Examination of the PARAGON-HF and EMPEROR-Preserved Trials."

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.

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, it really is so great to be back with you chatting about the papers here in the Journal. Thank you for going solo and for just being the greatest partner on earth. Thank you for that. For everyone listening in, we are back with some gusto and especially with this feature discussion today. You are not going to want to miss it. We are talking to Dr. Milton Packer as well as Dr. Justin Ezekowitz. We are going to compare PARAGON and EMPEROR-Preserved trials in heart failure with preserved ejection fraction. A really interesting discussion you're not going to want to miss, but now let's start with some papers in today's issue. I'd like to start, please.

Dr. Greg Hundley:

You bet.

Dr. Carolyn Lam:

Greg, you know the optimal duration of antiplatelet therapy in patients with high bleeding risk with or without oral anticoagulation after coronary stenting? Well, that still remains a question. Today's paper is a pre-specified subgroup analysis of the MASTER DAPT trial and reports on the outcomes of patients with or without an oral anticoagulation indication in this study.

Dr. Greg Hundley:

Right, Carolyn. Remind us. What was the MASTER DAPT trial? What did it test?

Dr. Carolyn Lam:

Ah. MASTER DAPT investigated an abbreviated or one-month versus a non-abbreviated or three to 12-month dual antiplatelet therapy and a stopping of antiplatelet therapy at six months strategy after coronary stenting in an all-comer population at high bleeding risk.

Dr. Greg Hundley:

Carolyn, what did this subgroup analysis of outcomes in patients with and without oral anticoagulation show?

Dr. Carolyn Lam:

At 12 months of follow-up, ischemic and net risk did not differ with abbreviated versus non-abbreviated anti-platelet regimens in both subgroups, although significantly fewer clinically relevant bleeding events occurred in the group without an oral anticoagulation indication. Whereas only numerically fewer bleeding events occurred in the group with an oral anticoagulation indication that did not reach statistical significance. This subgroup analysis from the MASTER DAPT trial really adds additional evidence that dual antiplatelet therapy beyond one month in patients with or without an indication for oral anticoagulation really has no benefit and only increases bleeding risk.

Dr. Greg Hundley:

Oh, very important finding, Carolyn. Great research. Well, Carolyn, how the extracellular matrix microenvironment modulates the contractile phenotype of vascular smooth muscle cells and confers vascular homeostasis really remains elusive. Thus, these investigators led by Professor Wei Kong at Peking University applied protein-protein interaction network analysis to explore novel extracellular matrix proteins associated with the vascular smooth muscle cell phenotype.

Dr. Carolyn Lam:

Huh. Interesting. What did they find, Greg?

Dr. Greg Hundley:

Right, Carolyn. By combining an in-vitro and an in-vivo genetic mice vascular injury model, they identified nidogen-2, a basement membrane glycoprotein, as a key extracellular matrix protein for maintenance of vascular smooth muscle cell identity. Nidogen-2 exerted its protective function via direct interaction and modulation of Jagged1-Notch3 signaling.

Dr. Carolyn Lam:

Wow! Nidogen-2 and Jagged1-Notch3. I always learn so much. What are the clinical implications, Greg?

Dr. Greg Hundley:

Right, Carolyn. Perhaps targeting nidogen-2 to precisely modulate Jagged1-Notch3 signaling, well, that may provide novel therapeutic strategy for atherosclerosis and post-injury restenosis.

Dr. Carolyn Lam:

Very nice. Well, in the next paper, we discuss inflammation in heart failure. We know that inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Interesting, huh? Well, these authors, Dr. Wollert and colleagues from Hannover Medical School in Germany, identified an adaptive crosstalk between inflammatory cells and cardiomyocytes that protects against persistent afterload stress-induced heart failure in mice. Monocytes and macrophages produced myeloid-derived growth factor in the pressure overloaded myocardium to augment SERCA...