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Circulation on the Run

Nov 5, 2018

James de Lemos:              Welcome everyone to Circulation on the Run my name is James de Lemos, I am the executive editor for Circulation based at UT Southwestern in Dallas and I will be filling in for Carolyn today as we discuss this year's surgery themed issue. I would like to welcome Dr Marc Ruel, the chairman of cardiac surgery at the University of Ottawa and a long-time editor of the Circulation of surgery themed issue, as well as Dr Tim Gardner, professor of cardiac surgery at The University of Pennsylvania and our leader at Circulation on the editor team for issues related to cardiac and vascular surgery. Marc and Tim, welcome and thanks for all your tremendous work in this issue.

Dr Marc Ruel:                    Thanks James for having us.

Dr Tim Gardner:               Thank you. Glad to be here.

James de Lemos:              Why don't we start Marc with your thoughts on how this issue comes together, how it came to be, you picked the papers and how we ended up with this terrific issue.

Dr Marc Ruel:                    It’s been a really important year for surgery and for this issue, as some of you may know the supplement which used to be the old designation of this issue has been changed to the surgery themed issue in about 2014 or so where the new Circulation leadership and what we tried to do every year is to bring the very best, not only of cardiovascular surgical science but also of clinical care and pearls around clinical and surgical care. So, I think this year we have had probably more than 60 submissions sent to us. Tim and I have looked at those very closely and you as well, James, we really wanted to get the feedback and the approach from not only cardiac surgeons but also from cardiologists and cardio vascular care specialist around those. We've tried to select the best of science and also some papers that we feel would be very useful with regards to providing new clinical pearls for surgeons and anyone in the circle of care around cardiovascular surgery.

Dr Tim Gardner:               If I could just add, James, of course we have other papers that have been submitted by surgeons that are published or that deal with cardiac surgical or vascular surgical topics during the year, this particular issue is very much focused on cardiac surgery but throughout the year we have plenty of submissions of manuscripts by surgeons about surgery about surgically related topics and so on. So, I am actually kept quite busy reviewing and commenting and consulting on manuscript submissions of Circulation. There are plenty of papers over the course of the year that relate to surgical topics.

James de Lemos:              Wonderful, I think you will see, as we talk about these papers, really that what Marc and Tim are talking about in terms of papers that are broadly relevant to cardiac surgeons and cardio vascular providers really rings true. Let’s walk through the issue, its set up like most of our issues begins with a couple of opinion pieces, a brief frame of reference, articles about important topics. Marc, do you want to talk about the Domanski paper, talk about revascularization for ischemic cardiomyopathy?

Dr Marc Ruel:                    Absolutely, we've asked experts, namely Mike Farkouh and Micheal Domanski, to provide us where their thoughts regarding the optimal treatment on patients with LV dysfunction and severe coronary disease. What many of us would call an ischemic cardiomyopathy, which may be construed as a misnomer or as an accurate term, I will not debate on this today, but certainly it remains a very vexing clinical problem. I think we could all agree that the last niche where we still see very high in terms of treatment for coronary disease this is probably mortality and kind of an inability to provide for a tangible result.

                                                Once LV dysfunction has set in and the present of CAD the outcomes are poor, and it took years and literally almost ten years for the STICHES trials to show a benefit for surgical treatment. This is relatively all study now and it has to be put in context and I then that Mike and Mike are doing this extremely well in terms of providing the caveat, for instance, STICHES at its inception added had a 5% mortality rate around CABG, so we know that the modern outcome are probably better than that. It’s very difficult to actually decipher what sound be the mainstay of treatment for each challenging patient and I think the frame of reference provided by Dr Farkouh and Domanski is extremely useful in helping with that.

James de Lemos:              Tim we have another frame of reference that is also provocative. Trying to make a case that we think about in patients with hypertrophic cardiomyopathy with obstruction early surgical procedures to relieve the obstruction. Do you want to tell the readers a little bit about this opinion piece and what your thoughts on it are?

Dr Tim Gardner:               Sure James, this is a really nice frame of reference article from both doctors Martin and Barry Maron and then their European contributor Paolo Spirito and the point of their opinion paper is that the surgical art for managing this very difficult obstructive cardiomyopathy syndrome has reached the point where we really shouldn't wait until patients are in extremist or in class 3 or 4 status in term of syndromic problems and can consider earlier surgery for these patients. They make the very important point which I think we have to except is that for patients to do well with this operation they need to be in a center where there is experienced surgery and experienced surgeons, but the point is now that the state of the art for managing obstructive cardiomyopathy is as such that good result are obtained and patients should be offered this surgery when appropriate, but earlier, in order to avoid the challenges of end stage cardiomyopathy and difficulty relieving the obstruction, so this is a really important opinion piece. It’s great to see our cardiology colleagues who are experts in this field make this point based on well published data from centers like the Mayo Clinic.

James de Lemos:              Moving now to the original articles, we've got 5 original articles, maybe Marc we can start with your thoughts on 2 articles related to revascularization, one in coronary disease and one identifying a really novel approach for treating type A aortic dissection with malperfusion.

Dr Marc Ruel:                    I think that's well said James, the first of these original papers will be likely somewhat controversial. The first author is Dr Bo Yang and essentially it is a series from Michigan where they look at just shy of 600 patients with acute Type A Aortic Dissection, of whom 135 were identified to have malperfusion syndrome. Essentially defined by the authors as something slightly different than malperfusion per say but really malperfusion accompanied with evidence of necrosis in one of the organs.

Their approach has been new and somewhat controversial in that they have brought these patients first to the interventional radiology suite in order to fenestrate in many cases or at least open the culprit artery or the culprit perfusion territory that leads to malperfusion syndrome and then depending on how the patient is doing they would then proceed to open repair as soon as 24 hours afterwards or they may wait longer in someone where there is no sign of improvement yet prior to moving to the ER, so they have found this has not only improved the results with regards to in hospital mortality after operative repair type A aortic dissection, but also to allow them to better discern or differentiate should I say between patients in whom malperfusion may lead to a futile situation and who then may be avoided from undergoing a very complex and difficult OR so would argue this is probably the first such large organized, well documented series of such an approach and I think it will lead to some head scratching, this being said it must be remembered that the goal standard for Type A aortic dissection is dealing with the intrapericardial aorta first and hoping that the perfusion gets better from this and everyone knows that the results of this approach are not fantastic.

We know that even in the best centers, including the latest data from Germany such an approach has about a 20% mortality rate so clearly there are ways that we can improve with Type A aortic dissection and this paper may be a strike in the right direction.

James de Lemos:              The other revascularization paper addresses that, I would say also a quite controversial topic which is how many atrial grafts are optimal in patients that are undergoing surgical revascularization?

Dr Marc Ruel:                    This is a paper from Toronto where the Ontario ICES database was used and several papers actually dozens and dozens of papers have come out previously from this well established and well allocated database. Steve Fremes who is the senior author and one of his trainees, Dr Rocha and the team of authors got together and decided to look at the impact of 3 versus 2 arterial grafts in patients undergoing cabbage with regards to survival. They have very nice, very compelling follow up information and they basically carry out 2 exercises.

First, they wanted to see if the 3,000 patients or so had 3 or more arterial grafts had a better outcome than the 8,000 patients or so who had 2 arterial grafts and frankly they found there was no significant difference with regards to survival at 8 years and freedom from MACCE at 8 years. However, when they compare those 9 or 8,000 patients or so who had 2 arterial grafts to the rest of 40,000 or so patients who had 1 arterial graft and completions with veins they found that again there was a survival benefit. This last finding is not new and its obviously subject to indication biases as well as expertise bias as we've seen in many of the observational perspectives studies around multiple arterial grafting. But I think the concept of comparing 2 versus 3 arterial grafts is very novel in surely in this paper is being addresses with very high scientific related from the numbers and the quality of the follow up that's been brought to the exercise.

James de Lemos:              I've really been struggling, I love your thoughts and Tim, your thoughts on how to reconcile the data in space. I really am having a hard time getting my head around what seems to be conflicting data about the number of arterial grafts in what an optimal CABG looks like in 2018 with the evidence that we have. What are your thoughts on that question?

Dr Tim Gardner:               I think that this supports the concept that 2 arterial grafts whenever possible for some patients, younger patients perhaps 3 but I think the important point is, multiple arterial grafting should be attempted and carried out whenever possible. I leave the is 3 better than 2 to some future study or future review that can be more precise about that.

Dr Marc Ruel:                    This being said I think we don't view efficiently coronary surgery as being an area of expertise and many centers including very strong academic centers may not necessarily marry the concept that coronary surgery has to be something with the dedicated expertise. I think when we look at those observational perspectives series we see the effect of it may be the expertise bias, but it may be more than just 2 or 3 arterial grafts, they may be the whole wrapping of care that comes with it including optimizing beta blockers and managing diabetes etc. So, I think it may be more than purely conduits but definitely, as Tim said, 2 arterial grafts are probably better than just 1 and the jury is still out on whether 3 is better than 2.

James de Lemos:              Excellent. Switching gears now Tim, an area that obviously you have tremendous experience and expertise we've got 2 innovative papers addressing surgery for individuals who have congenital heart disease. Can you update us on what we are publishing here?

Dr Tim Gardner:               Sure, the one study focuses on the risks of pulmonary valve surgery in adult patients who underwent a correction of tetralogy of Fallot earlier in life. This is a growing population actually we refer to as young adult with congenital heart disease and in many centers they are more numerous in terms of the patients groups than infants because this group has been successfully treated early in life, but this particular group of patients, patients who have had tetralogy of Fallot repaired and end up with what the author calls right ventricular outflow disfunction generally regurgitation through the outflow tract pulmonary valve sometimes obstruction, these patients then face significant clinical challenges in death from heart failure, right ventricular failure or arrhythmias in their late 20's and 30's. We have been focusing now on the timing and the type of pulmonary valve replacement.

Dr Tim Gardner:               Now there is catheter replacement options available, but when to do this and how to minimize risk is really the focus of this one paper that describes a four multi-center study looking at predictors of risk for these patients. Sort of a hypothesis generating paper, but it is an important study none the less, focusing on how to identify patients with right ventricular out flow tract dysfunction and who should have pulmonary valve replacement and when that should optimally be done. It a very good study. The other important study that we have is that the other age spectrum of neonates and this is a study that is based on a review of data from the pediatrics heart health information systems database, led by the group at the Children's Hospital Philadelphia.

Looking at variations in pre-operative care and management of neonates with transposition of the great arteries. This was a little controversial actually when we reviewed it among the editors because the suggestion is that earlier surgery this would be in the first week of life and more perhaps aggressive use of atrial balloon septostomy seems to improve outcomes. This is a generally low risk population, the point of the paper is that these pretty good results can be improved by paying more attention to the timing of surgery and the appropriate use of balloon septostomy. It’s sort of a quality improvement perspective based on a large database and I think it’s a very nice study and undoubtedly creates additional attention to this particular area.

James de Lemos:              Marc, our last original paper is a really novel issue engineering approach to creating vascular conduits, can you tell the readers briefly what happens to her in this paper?

Dr Marc Ruel:                    Indeed. It’s a paper from Stanford, from Joe Woo’s lab and the first author is Daniel von Bornstädt. Essentially, as you say it’s a very innovative novel approach to try to recreate a bioengineered blood vessel. We surely know there's quite a need for such off the shelf conduits, not only in cardiac surgery but also in vascular and vascular surgery and even for things such as AV fistulas and others. It’s really interesting to see that this is what I would call transitional science at its best and surgeons have had an important role over, as you know, centuries in helping develop this and many discoveries have come from surgical labs, especially a few decades ago.

In any case, what Joe and his team have performed is to try to use clinically applicable methods to derive and create a bioengineered blood vessel and they started first with human aortic smooth muscles cells and skin fibroblasts which are literally easy to get and they used those to constructs bi-level cell sheets, they then used a 22 gauge angiocath needle so that the sheets would be wrapped around this in order to lead to a tubular vessel construct. Then the next problem has been traditionally that those bioengineered vessels would burst out with atrial pressure. What Joe's team came up with is to use a commercially available adhesive, so a glue essentially, which is dermabond which typically we use after any form of surgery to keep the incision together and they put dermabond on the surface of this sheet wrapped around an angiocath needle to act as a temporary external scaffold. They then led this into a bioreactor and implanted it in series of 20 rats as a femoral artery interposition graft. The results were excellent. Essentially, patency was perfect and there was a full vascular maturity with all 3 layers of blood vessel that you would expect including an intima that had been formed as a result of the experiment.

I think this is all very promising because none of the methods here are involving something that would have non-autologous issues, or you could easily see this being used with a patient’s own cells in order to achieve an autologous. I think this is obviously small vessels, there are 22-gauge needle is not a big conduit, you’re not going to bypass an LED with this, but I think it’s a start and it’s all done using transitional or clinically applicable methods. I guess the next step would be moving to a large animal model and certainly I think we should stay tuned to see where this leads us.

James de Lemos:              I think that's exactly my thinking as well about that discussion and really leads us into some of the issues that come up in the review paper that you are a co-author on new strategies for surgical revascularization. I think this basic in translational science piece is designed to address some of the limitations of current revascularization and you all did a really beautiful job covering some new more clinically ready strategies in your papers. Can you just tell us very briefly what you all covered in that review paper?

Dr Marc Ruel:                    Indeed, this is a paper that was kind of aiming at being a state of the art around CABG and rapidly the focus was reshaped towards kind of new strategies around surgical myocardial revascularization. Initially we have a section on OPCAB on this and that and minimizing the inflammatory effects of the pump and quickly it became apparent that the desire of Circulation and this themed issue was to focus it more on really what are the up and coming improvements around surgical coronary revascularization. This paper focuses on essentially 4 main areas. One is hybrid coronary revascularization, the second one is less invasive coronary surgery, the third one is the use of multiple arterial grafts to which we eluded a little earlier during this podcast and fourth is the use of an aortic coronary surgery, essentially meaning bypass surgery performed without any manipulation of the aorta.

James de Lemos:              As we think about innovation in terms of conduits, the procedure itself, the other aspect that's covered in our last paper is can we make the procedure safer perhaps by modifying our use of anti-platelet therapies based on meshment of the platelet phenotype and Tim do you want to bring us home by just telling us a little bit about what we learned from Paul Gurbel and his group of platelet experts?

Dr Tim Gardner:               Well we learnt a lot about platelet science and appropriately so Dr Gurbel is a well-recognized expert in platelet physiology or platelet management and this is a really quite a challenging area because many of our patents come to surgery especially for coronary surgery already on platelet inhibitor agents and what Dr Gurbel and his co-authors showed in this paper is that although there is somewhat limited data there can be and should be platelet function testing and with an appropriate understanding of platelet inhibition drugs that we may be able to limit the time between removal of these or discontinuation of these platelet inhibitor drugs and the necessary surgery which will improve outcomes and reduce bleeding in patients requiring urgent CABG surgery. It’s a very useful update and it is a good example of a paper that isn't written by surgeons, but really applies very much to the cardiac surgical treatment of coronary artery disease

James de Lemos:              I really like the very practical tables and figures that lay out the potential tests that surgeons or anesthesiologists may consider for assessing this and even how one might implement. I would like to bring us to conclusion now, first I want to acknowledge, Sara O'Brien at the Circulation office for her amazing work together with Marc and Tim pulling this issue together, making sure that we have a consistent high quality issue with wonderful figures and tables and it really came together beautifully and thank you both for joining me today and the podcast I think it’s obvious that we've got an issue that all of you listen to this podcast need to actually pull out the issue or download it because we have a co-host of wonderful papers to look at and cardiac surgery thriving at Circulation. As we've talked about this is the tip of the iceberg, this themed issue, we've got great content coming, issue after issue. We are already open for business next year’s issue, so please send us your best cardiac surgery research. Please pay attention to these important papers and apply them in your practice because I think many of them are already directly applicable.

Marc given your leadership role in the issue do you want to bring us home and make any concluding remarks?

Dr Marc Ruel:                    I think your points are very well taken James and I want to reintegrate that if I speak on behalf of the cardiovascular surgical community, we are very thankful to the leadership with Circulation. James, Joe, Tim and many others and obviously the support from the staff in clearly establishing that cardiovascular surgery is a very important therapeutic mentality and the overall scope in the broad scope of cardiovascular therapeutics.

Dr Carolyn Lam:                You've been listening to Circulation on the Run. Don't forget to tune in again next week.