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Circulation on the Run

Oct 5, 2020

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, and in the second comparison, looking at the radio versus 225 patients, there was a patiency advantage for the radio Herceptin in Spain.
But partly because the comparison was less power than the first, there was no major adverse cardiac event or even mortality difference. So I think again, aligns with the data that we know the arc trial, as we all know, 10 years was neutral. There was no benefit to internal thoracic arteries versus small one, which regards to anything repeat revascularization based mortality.
And we know have 10-year data recently published that shows that the radial artery in pooling patient level data from many randomized clinical trials leased their survival benefits. So I think it's fair to say based on available data now with this team issue in 2020 in the fall, that the best second RGO is very likely or radio RV and too many people surprised.

Dr Timothy Gardner: Yeah. If I could just add my perspective, there's an editorial by Steve brings on this. This really does solidify the data about long-term radial, artery patency. And that was when I came away with, it's not so much the comparison of the radial on the right internal thoracic, but the fact that the radial artery would be like held up very well.

Dr James de Lemos: If you're referring a young patient or considering a young non-diabetic patient for cabbage at this point, was you select a radial artery or right internal memory?

Dr Timothy Gardner: Well, I probably would favorite as a second graph the right internal thoracic artery rather than. As a free graph, but I certainly wouldn't hesitate to use the radial artery as the second graph there as a third grade. My competence in the radial artery continues to grow in this report reinforces that.

Dr James de Lemos: Excellent really important study for both the cardiac surgeons and the cardiologists that read our journal.
Let's switch gears and talk about bowel surgery, Tim, the camera Cardiolite study drills deep into different strategies for repairing the mitral valve. What did we learn there?

Dr Timothy Gardner: Well, first of all, this study, which comes from Mark Raul's unit Benson Chan being the first author and address the issue that repair with resection of the mitral valve made me to functional stenosis of the valve. And that has been a concern among surgeons and that has led some surgeons to prefer non-lethal the resections repair. And this study was very carefully done and actually demonstrated that the data did not support the fact that resection versus preservation is this okay with the riff? So I think that, you know, there are various ways to repair the valve. And if you go back to the original descriptions of mitral valve repair resection was a major component for many people in many studies. And this is a reassuring study that either approach appears to be effective without badly under sizing the annulus that there should not be residual mitral stenosis.

Dr James de Lemos: Tim is one of these materially easier to do in the operating room. So then it would emerge as the preferred therapy or is it really going to be surgeon dependent.

Dr Timothy Gardner: I think it’s fairly surgeons dependent. I mean, we have technical variations for a lot of operations, and I think it's when the surgeon is comfortable with Mark. You might want to comment on that point.

Dr Marc Ruel: Yeah, I agree with both of you. I think it's very reassuring because there's the orientation of where the last issue is. Small. The patient's exposure is not knowing that you can use theater technique and in some cases not have to go on to the pathway. We Muscle is a reassuring avenue. So I think every surgeon has her or his preference, but it's nice to know that both these can be used interchangeably without any drawback to the patient.

Dr Timothy Gardner: Let's switch gears and talk about a paper that I think has pretty profound implications for both of our specialties. And this is an observational analysis from the RS trial, evaluating the association of postoperative atrial fibrillation in the long-term risk of stroke. Mark, what did you think of this paper and its implications?

Dr Marc Ruel: This is a very interesting piece that comes incidentally from the heart trials. So non related to what we were
Just discussing before the 3000 patients or so of the art trial were followed at 10 years. Mostly with regards to major adverse cardiac events, et cetera, anything that's related to the question at stake at the time, which was single internal for us, incidentally, the authors have ready data regarding the incidence of stroke at 10 years. And they were able to use those and go back to those stations who have postoperative atrial fibrillation and see if there was a correlation, even when accounting for other factors in the patient profile. So interestingly about 24% of patients have had post-op and post-op you, is defined in variety of ways for this particular study, it was defined as 30 seconds at least of atrial fibrillation or atrial flutter during the index hospitalization after the operation. So I think this is a very fair and square type of definition and those patients and those who have the CBA incidents by 10 years was 6.3% versus those who did not have postoperative 3.7%.
So this is obviously a significant numerical and also statistically significant higher risk for those patients who have post-operative a-fib. So there's a number of caveats around that. All the risks for post-doc are often the same ones that may lead to the risk of stroke over the long-term. So I think we should see this not as probation. But that should be not even as an association. But certainly as a correlation, but it is really unique data that has not been produced before. Like postoperative is so common after cardiac surgery. It affects many of the patients that both the cardiology and cardiac surgery individuals have to treat.
And I think the more information on it, the better, there were a number of interesting observations warfarin, for instance, even though the incidence of post-op 24% was used in only about 8% of the overall trial. So one may debate, have these patients being anticoagulated enough also, would there be a way to provide enhanced surveillance to patients who have post-op in order to maybe catch them prior to them having a cerebral aspir event?
So I think it's really very interesting data. I would like to briefly provide one last tidbit of information, which I thought was very, very fasting. So the authors used the CHADS two score in order to kind of ascertain your overall risk attributed to which regards to stroke in those patients. So this is probably the latest and best iteration of the Chad score if you will.
And they found that in patients with a score of less than four, so it was zero to three. There was no difference with regards to the incidents of CVA or in signers versus those who have post-op after the operation. However, when the score rich four or higher. This is rare to you where the risk was concentrated. So that particular cohort of patients seemed to be the one where I think the efforts with subsequent studies should be concentrated in order to intervene and hopefully catch these patients who may have atrial fibrillation without having it.

Dr James de Lemos: Does this change your practice at all? Do you think, I mean, I guess it's interesting for me because obviously I see a lot of these patients back from surgery and I've tended to candidly ignore short episodes of peri-operative atrial fibrillation. And this really raises questions as to whether that approach is wise and needs to be revisited.

Dr Timothy Gardner: I agree completely on the other hand, I think that targeting patients, I mean, I think the last point that Mark made about the patients that ended up with problems with higher AFib and with consequences had other risk factors associated with their risk of stroke. So this continues to be a really tough group to manage. I think that one question that we all have is do the, the, the new novel oral anticoagulant agents provide better long-term protection. As a topic for another important study that should be coming down the pipe pretty soon.

Dr James de Lemos: And I'll just point out to our listeners that at the American heart association meeting in November, that late breaking trial will be presented called search AI cardio length that will evaluate extended monitoring creature fibrillation after surgery. And I think that will build off, of this theme that perhaps atrial fibrillation after cardiac surgery is a more important tissue than many of us considered.
Let's move to the next paper, Tim, this is really right in your wheelhouse in terms of surgical. So specialization. And this is an interesting paper. I thought evaluating variation and congenital heart surgery outcomes across centers in the U.S. and this group really evaluated a large proportion of dissenters doing congenital heart surgery in the U S.

Dr Timothy Gardner: Yeah, absolutely. And they made use of the STS database. They've got good data and it is a multi-institutional review group, really looking at how to optimize outcomes. And I think that, the assumption is that regionalization with more attention to high volume centers, especially for the most high risk say neonatal heart surgery is the way to go.
But this study actually while demonstrating significant hospital variations also demonstrated that and reading their conclusion. Now a substantial portion of potential improvements that could be realized on a national scale are related to variability among lower risk patients. And this makes me think back to Dr John Kirkland, who was maybe the first one in our field to actually develop a checklist of important steps and management strategies during the surgical procedure in the early post-operative period.
He worked with IBM on that. And I think that lesson here that I take away from it is that volume may be important, but not just for the high risk neonatal population, but for all congenital heart surgery patients. And it really is an important specialty. And there may be some opportunities for improvement just by standardizing sort of management of even the lower risk patients. This is one of several reports from this multi-institutional group that is focused on data from the STS database in congenital heart surgery. Good job demonstrating these variations in outcome.

Dr James de Lemos: Yeah. And I think tremendously important, right? Because these lower risk in general procedures may be more like other procedures that cardiac surgeons do. And I think you make a great point that these systems based approaches to minimizing variation do seem to matter. And I wouldn't have thought that the, this is another one of the theme really here in the issue where we have a lot of studies that are challenging the way we thought about, common medical and surgical problems, really a fascinating piece.
Let me take a moment here to introduce a new member of our team for the themed issue. Mike Fischbein, who's a surgeon scientist at Stanford, a practicing cardiac surgeon on the faculty there, but also runs a large and very successful basic science laboratory. And he has joined the surgical team for the themed issue to add his particular expertise in the evaluation of the basic science papers.
Mike, welcome to the team. I think our readers and listeners will really benefit from having your perspective. And I'd like to have you now please talk about the basic science papers here in the issue.

Dr Michael Fischbein: Thank you very much, James. It's really a pleasure to be part of a team. The paper that I'd like to discuss today is a feature of basic science paper entitled a Single cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns and Control and Aneurysm Human Aortic Tissue. This is from Scott LeMarie group from the Department of Surgery at Baylor College of Medicine. I think this study is very important. It's focusing on the ascending, thoracic aortic aneurysm, as you know, ACE and aortic aneurysms are the second most common aneurysm after abdominal aortic aneurysms. One of the risk factors of ascending aortic aneurysms is that as they grow, they can tear dissect or rupture.
Both of which are life-threatening currently the only treatment option is prophylactic surgery. And this is really based on size criteria alone. Now, while over time, we've established that smooth muscle cell loss and exhale and matrix breakdown are important during this process, really the molecular mechanisms or pathophysiology is poorly understood. Therefore, limiting development is novel drug regimen, and this manuscript, the authors use single RNA sequencing to compare the aneurysm wall to normal control. Aorta is taken from transplant recipients. One of the benefits of single cell RNA sequencing is that allows one to identify the cellular components or heterogeneity within the aortic wall. And it also allows us to see the aneurysm relevant transcriptome changes in the major vascular cell types within the aorta. The authors identified 11 major cell types in the aorta, including a number of different smooth muscle cell subtypes and to Celia's cells, fibroblasts and inflammatory cells, including T-cells and macrophages.
They found over 500 altered genes comparing the aortic wall to normal control. Mitochondrial dysfunction seemed to be altered in several gene types and they identified a transcripted factor ERG, which stands for Erythroblast Transformative, specific Related Genes to be important in maintaining the normal aortic wall function. And this was reduced specifically in smooth muscle cells, fibroblasts and endothelial cells. This is really an exciting target that may lead to drug development in the future. So thank you very much, James, for allowing me to participate in the group. And I think this will be an exciting paper for the readers.

Dr James de Lemos: So Mike, thanks so much. Really appreciate your perspectives here. Another really interesting area that is quite forward-thinking Mark is this idea of 3D printing. Theotic roots and conduits. Tell us about this paper from Joe Woo’s group.

Dr Marc Ruel: This is another great contribution from Joe's lab. Looking at the issue around bell spring, and many would call it bear hair because essentially they preserve and surgeons go to great pain and great strides to try to recreate if you will be normal slash nets, these geology and aortic root sinuses. And many of us, when we do this operation are taking great minutia and creating those. And there's a number of things that happen. And all of these techniques vary from the more approach of just taking a straight to, and essentially reinventing the native aortic valve and connecting the coronary buttons. So Joe's lab wanted to study this with regards to the translationally relevant outcome of opening velocity and closing gossip with regards to the RP pal.
And they've done this 3D printed biomechanical study, aware they have used for signing LT. Val, that'd be put into these different configurations, some including Neil, if you will, some including what we call a bell solver type of breath and using the natives or signing as a control in the same 3d biomechanical model. And essentially the conclusions of the study, which is free, elegant be performed and Bree compelling from a data point of view is that a simpler appears to be better too many.
I'm sure the investigators I'm sure what will be many readers price. These trade routes' configuration without Neil sinuses seem to have the lowest coast opening and closing velocity. So it would suggest that this may translate into longer term durability of the valve. Now, there are other reasons why someone, for instance, the one I do this operation, I like to use Valsalva graft. It's not because I so strongly believe that Neo sinus type should be there is because it also gives enhance an easier reach to the corny about adding a vertical followed by a horizontal type of pattern I find is a bit more reliable and it may not really matter what the opening and closing philosophies are because those files are not intrinsically abnormal.
So they may last for many decades going forward. But nevertheless, I think this is a very important study and series of experiments, and we're very happy to include it in the theme this year.

Dr Timothy Gardner: Yeah. And if I could just add the thing that I admire most about this study is that not just how they come up with this innovative, 3D printing way to model, but the team included mechanical engineers and bioengineers at Stanford, and that's adding real substantial science to what some surgeons have theorized about. So this is a small study, but the results are quite interesting. Let's talk now.

Dr James de Lemos: It's about this remarkable Primer that we've had on critics, transplantation. This is something I wouldn't have imagined five years ago would be something we'd have even considered close enough to clinical application to publish in circulation. But what's different about this now and what should our readers look to in the future with this technique.

Dr Timothy Gardner: This paper comes from a group at the Mass General [Hospital]. They've continued to work on Xenotransplantation as a possible solution to the need for new donor organs. And I think the most remarkable thing is after almost silence for 10 years, they have outlined the possibility much more realistically now of coming up with Xenotransplantation as a usable alternative, based on some very important basic science work that others have done in baboons and that they have model into additional experiments. This is what was a very informative article for me. And it's still some ground to cover, but they've really worked away at the science and think that they believe that they're nearing the point where they know transplantation or for cardiac replacement is a possibility. Again, amazed I sort of thought Xenotransplantation was an impossible dream 10 years ago. And here we are, perhaps at the point where it is more of a realistic possibility.

Dr James de Lemos: Really remarkable. When you think about these technologic advances that are getting so much closer to clinical application. Well.

Dr Timothy Gardner: Thank you both. I'd like to take just a moment to recognize Sara O'Brien in [the] Circulation Editorial Offices in Boston for her remarkable contributions yet again, to pulling this issue together and keeping Mark and Tim and Mike and myself on task to bring this issue home. And thank Mark Tim and Mike for pulling together. What I really believe is far and away, our finest issue. We're talking here in my opinion about multiple studies that changed the way we think about cardiovascular surgery and its complications, including atrial fibrillation that affects all of us in cardiovascular medicine.

Dr James de Lemos: Marc, would you like to make some final comments as we wrap up today?

Dr Marc Ruel: Absolutely. I could not agree more with your statement, James. I think this is a team effort and I want to be cognizant to the leadership of Circulation for as the premier cardiovascular journal, recognizing the importance of cardiovascular surgery in the field and dedicating an issue through what is best that's happened over the last academic year or so. We want this issue to continue for all time. And I think it's very well started and it's growing nicely. And thanks to the efforts of many, including of people on this call today. I hope that our readers will like it and I foresee it will garner interest even beyond the strict fields of cardiovascular surgery but to the entire cardiovascular community.

Dr Greg Hundley: This program is copyright American Heart Association, 2020.