Circulation October 2019 Issue

Dr James de Lemos:        My name is James de Lemos. I'm the executive editor for Circulation and I'll be filling in today for Carolyn Lam and Greg Hundley, and delighted to host the podcast for the annual cardiac surgery themed issue. I'm joined today by Tim Gardner from the University of Pennsylvania who leads the surgical content in Circulation year-round, as well as by Dr Marc Ruel, who's the guest editor for this issue and the Chief of Cardiac Surgery at the University of Ottawa and has really led the development of this issue. Marc, Tim, welcome.

Dr Timothy Gardner:      Thank you.

Dr Marc Ruel:                    Thank you. Good afternoon.

Dr James de Lemos:        And Marc, thanks for all you've done to bring this issue home again this year. It's really wonderful to see this thing develop. Why don't you start us off and tell us how this issue came together and what the purpose of this is? Why do we publish a specific issue focused on cardiac surgery?

Dr Marc Ruel:                    We're really delighted that Circulation has taken the stance as the cardiovascular community's premier cardiovascular journal. I think as an important piece of this is the fact that cardiovascular surgery already has a resurgence intermediate with importance despite new percutaneous options and medical therapies available. There's more and more patients who find himself in need advance path if you will, of an advanced cardiovascular disease and surgery can be performed with safer and better outcomes constantly.

                                                So, I think this issue obviously aims to gather the very best of cardiovascular surgery, not only including cardiac surgery, but also there's actually one of the papers on peripheral vascular surgery.

Dr James de Lemos:        We'll start Tim with you if you don't mind. I'd like to talk about two papers. One from Stanford that focuses on inter-facility transfer of Medicare patients with Type A dissection and then a research letter that studies hospital volume effects with abdominal aortic aneurysm surgery from Salvatore Scali and colleagues at the University of Florida. Can you walk our readers through these papers and lead the discussion on these?

Dr Timothy Gardner:      The first paper focused on inter-facility transfer of Medicare recipients with Type A dissections. First off, underlines the fact that this is a very difficult, serious condition with mortality rates in this series there ranging between about 22 and 30%. And the purpose of the study was to analyze how these Medicare patients with acute aortic Type A aortic dissections are managed and whether the effect of high or low volume hospital experiences influences the mortality. As I think we might expect, patients who receive care at high volume aortic surgery centers have a lower mortality. Then the question is, what is the effect of transfer from a low volume or from a hospital without aortic surgery capabilities? What is the net effect there? The benefit of care and a high volume hospital is pretty clear. The mortality rate is significantly lower and the need to transfer or the actual fact of transfer does not increase the risk to the patient.

                                                It's an interesting challenge because we do know that patients with acute aortic dissection, if their repair or surgery is delayed, we'll have a predictable accumulating mortality. However, what this study shows is that the benefit of transfer and the importance of experience with this complicated aortic surgery. And it really brings up this very challenging issue of regionalization, of acute care or specialized care.

                                                We really struggle with this in so many aspects of surgical care, medical care in general, but especially procedural care. We realize that we need to be able to provide emergency care in many areas and we don't want to suggest that that smaller hospitals may not be able to care for patients with acute complex illnesses. But on the other hand, if transfer can be accomplished and if the availability of high volume experience can be achieved, that this is something that we really need to look at carefully. I think that this study brings that into pretty good view.

Dr Marc Ruel:                    James, I think that Tim has already captured the essence of this paper. The results are impressive in this excellent series and the really carefully led analysis. This is an important paper and it's very thought provoking.

                                                There’re two clans among surgeons. Those that believe that every cardiac surgeon who was named as such should be able to perform safely aortic dissection repair and another client and somewhat sustained or supported by the data from this paper that says that this is a special expertise that should be or regionalized and put through centers of excellence. So this paper would support the latter theory.

Dr James de Lemos:        The next paper, which was a research letter, sort of adds fuel to this fire of regionalization, doesn't it? At least insofar as we're talking about the more complex procedures.

Dr Timothy Gardner:      Yes, this paper studies the hospital volume effects on surgery for abdominal aortic aneurysms, an even more common and somewhat less lethal, but very morbid condition. And this analysis of center volume for care of these patients is complicated even a little bit more because as we know, endovascular repair of abdominal aortic aneurysms is now the most common form of treatment.

                                                Interestingly, in looking at the outcomes in a variety of centers with varying volume procedural volumes, there was no difference in outcomes when endovascular repair was done, but there was inverse relationship between volume and outcomes after classical surgical repair. This really highlight a change that's occurring in vascular surgery where, with endovascular repair being done more commonly, surgeons are having less exposure unless experience with open repairs. This is particularly a challenge for training programs where you have a surgical resident or fellow for two years and he or she may experience relatively few open repairs.

                                                So, this again, the data seems to suggest that higher volume vascular surgery centers, where the numbers of open repairs are done, have better results and that this is not nearly as much, in fact, it wasn't an issue for endovascular treatments, but it again highlights the procedure of volume outcomes relationship. I think this is something we're going to have to deal with both in terms of optimizing patient care, even considering when we're training new or young avascular surgeons, they may have to move to different centers to ensure that they have the kind of exposure to classical surgical treatment for those complex patients who are not candidates for endovascular repair.

Dr James de Lemos:        Let's change gears. We've been talking about two systems of care issues, but let's get back to the complicated patient themselves and talk about a paper Mark from Kato and Pellikka from Mayo Clinic, focusing on hemodynamic and prognostic impact of concomitant mitral stenosis in patients undergoing surgery or TAVR for Aortic Stenosis.

Dr Marc Ruel:                    As you say, this is an intricate clinical problem that we not uncommonly meet when we provide care for patients who have severe aortic stenosis. These are not young patients. These patients in this particular series of 190 patients with severe aortic stenosis, they also had some significant degree of mitral stenosis. These are patients that had a mean age of 76 years. I think we've all encountered these patients estimations, so someone has severe aortic stenosis and has some form of calcific mitral stenosis. And indeed in this series, more often than not, the vast majority of those patients had calcific MS as opposed to a Rheumatic MS. So, a different type of pathology probably to what we see in the elderly patients coming in with some degree of inflow obstruction.

                                                So, the authors took their 190 patients, mostly from the Mayo clinic, but also from Tokyo, about five patients contributed from Japan, and matched in one to two with some controls who also had the same degree of severe aortic stenosis, the same age, same gender, same left ventricular ejection fraction, but didn't have mitral stenosis. And then compare their fate over a couple of years. Essentially, what the authors found is that in patients with severe MS, which was defined as a trans-mitral gradient of equal or higher than four millimeters of mercury, the midterm survival was decreased. The hazard of death was increased by about 90% or so. And there was also a classification, the sub classification based on the fate of the patient with regards to the echocardiographic findings, as to whether the patient truly had mitral stenosis at the time of presentation. So prior to the aortic valve replacement or whether the patient had pseudo-mitral stenosis. How the authors classify this, is those patients in whom the mitral valve area remained less than two centimeters square before and after aortic valve replacement were classified as having true mitral stenosis.

                                                The authors provide a number of maybe predictors, if you will, or correlates perhaps a more appropriately termed as such, of patients who would be generally believed as having true mitral stenosis. And these included, for instance, in the mitral valve area was less than 1.5 centimeters square at the time of presentation, if calcium involved at both the anterior and the posterior leaflet on echo. And there was also the concept of Andler excursion. So, basically the distance between the apex and the analyst of the mitral Valve, half of the patients had true mitral stenosis and the other half saw an increase in the mitral valve area above two centimeters squares after aortic valve replacement.

                                                I think still that we don't have an answer to the question as to whether the mitral valve should already be intervened upon in this series. It was an observational series, so there's no arm where the mitral valve was actually intervened on, and we know that often this intervention is not easy to do if it's by TAVR, there's not a lot we can do on the aortic valve and if it's at surgery, often these patients may have extensive mitral annular calcification, which is not an easy undertaking to fix at the time of surgery.

                                                So, whether these patients, even the ones with true MS are better served by just addressing the aortic valve or adding a mitral valve intervention in addition to the AS treatment still remains an unresolved or unanswered question. But I think this paper helps tremendously with regards to identifying patients who may have the true mitral stenosis concomitant problem at the time of presentation with a severe AS.

Dr James de Lemos:        This was news for me actually. The high prevalence of pseudo MS in this context, I think many of us are very familiar with this with aortic stenosis and low output, but to see this in the context of serial valve lesions was really instructive for me. Tim, what are your thoughts?

Dr Timothy Gardner:      I think this is a really important observation to remind ourselves of in this TAVR era. If you have the heart open and you're doing the aortic valve replacement and you notice this, you can get a picture of this severity of the mitral stenosis or the mitral valve involvement, but I think that in the TAVR era, this finding, this possibility of significant mitral stenosis related to a more severe aortic stenosis has to be accounted for and taken into account.

Dr James de Lemos:        Excellent. The next paper I'd like to talk about is another original article from Shudo and Joe Wu at Stanford. Remarkable series really of almost a thousand heart-lung transplants that were done and reported in UNOS. Tim, can you walk us through this paper and its implications?

Dr Timothy Gardner:      heart-lung transplantation was done first at Stanford and actually by one of my close colleagues. Bruce Reitz in 1981. It was a really an operation and in the tradition of the innovation there in transplant surgery at Stanford. The operation, primarily for patients with end stage lung and heart disease, was done reasonably often at adventuresome and well-experienced transplant centers in the eighties and nineties and it's used less often today because we found that even in patients with end stage lung disease and concomitant ventricular failure that many of those patients can be treated successfully with double lung transplantation.

                                                So, that has resulted in a decline in use of heart-lung block transplantation. The other problem is that as they mentioned in the article that a donor becomes available and you can get two or three patients treated by taking the individual lungs and the heart for three recipients rather than using the whole block for one. That's been another reason why it's been harder to get these heart-lung blocks. But for some patients with end stage heart disease and irretrievable lung disease, this is a great option. There's a few patients with end stage congenital heart disease who have developed irretrievable Eisenmenger's complex with severe pulmonary irreversible form of hypertension who are still candidates for this, but this analysis of the 30 year experience at Stanford and using the UNOS database as well is very interesting and shows the importance of donor selection as a really significant effector of outcomes.

Dr James de Lemos:        Yeah, well I was also struck by the recipient factors too. It looks like selection in both directions is so important. The group that was remarkable to me was the markedly poor outcomes in the group that had heart-lung transplant after ECMO, that five times increase in mortality. That really struck a chord, particularly given what we're seeing now with ECMO accelerating somebody's status on wait lists. I don't know Mark or Tim, do you want to comment?

Dr Timothy Gardner:      That's a very useful observation and where an individual patient ends up on the acuity list as a potential recipient with UNOS rules, it is ECMO support does get them to a higher level of urgency and yet, as is shown in this series, the morbidities or co-morbidities associated with a patient who requires ECMO support prior to transplantation is pretty consequential. And as you said, those were the features of the recipient, the degree of co-morbidities or co-morbidity complications also impact the outcome.

                                                We're still struggling to find the best way to deal with rescue patients both with mechanical support and with transplantation, organ transplantation, and even in the case of heart failure, with destination therapy with mechanical devices, we're still struggling in an area where the challenges are high, and the best practices are not always as well clarified as we would like.

Dr Marc Ruel:                    And I would echo those concerns. I think the prohibitive results that we see after ECMO reflect the reality that there's not a lot of intermediate therapies available for patients who require heart-lung transplants. We have them for the heart now. We can move from ECMO and not go directly to an LVAD or to a transplant because we have implantable axial devices that can be put in percutaneously and basically can arrest the inflammatory response and the major cascade derangements that we see with ECMO.

                                                Unfortunately that is not available to replace both the heart and lungs, so I think there's still some medical advances, surgical advances that are necessary to bridge the gap because that gap right now is real and it's not a gap, it's a cliff.

Dr James de Lemos:        Great discussion gentlemen. Let's talk next Marc, about a research letter that was a case series from Cleveland Clinic from Donnellan and Desai, focusing on a fairly large group of individuals that had received mediastinal radiation therapy previously and then underwent valve surgery for radiation-induced valve disease.

Dr Marc Ruel:                    We were happy to receive this research letter from the Cleveland Clinic because clearly that institution, and maybe a few others around the world, have a special expertise in dealing with the uncommon, but very, very challenging issue of patients with the surgical radiation-induced mitral valve disease. And in fact, radiation-induced carditis. On average, these were patients who were seen about 17 years after their chest irradiation and I guess the main message that can be seen from this paper is that there's often multiple cardiac issues in those patients. They don't just have, for instance, a single valve, in this case the mitral valve, being affected. But the vast majority all tolled of around 80, 85% of patients required not only either another valve, but valve plus bypass or bypass surgery to be performed as well.

                                                So, there are clearly patients where there's been a lot of physical/irradiation damage, not only to the mitral valve, but to the entire heart. It's also, when you look at this series of these 146 patients, you can see that many had an increase in the right ventricular systolic pressure on echo and probably some degree of RV dysfunction as certainly we've seen episodically in our practices.

                                                So, hospital mortality outcomes are pretty good, but the results are humbling. 51% mortality at 2.8 years. And these patients were on average 60 years of age. So looking at U.S. life tables, when someone's 60 years, I've made it to 60, they usually have at least another 20 years on average to live. But these unfortunate patients, despite their cardiac operation performed, having been performed safely, have about an 18% death rate per year.

                                                I think the jury's still out as to which are clear indications to offer these patients surgeries with the humbling results that we see even at a center of excellence by the Cleveland Clinic. But I think this is a foray into a very difficult cardiac problem for which there was limited literature before and certainly that's something that's very relevant as we refer to very advanced cardiac surgical therapies for patients with advanced disease.

Dr James de Lemos:        Mark, you're actually a coauthor on our State-of-the-Art piece, evaluating arterial grafts and CABG, reviewing after the publication of art and radial. What were the main conclusions from your review and interpretation?

Dr Marc Ruel:                    Essentially, there's a discrepancy right now with regards to the use of multiple arterial grafting. The observational series have almost uniformly showed that patients who receive multiple arterial grafts live longer and do better, et cetera, but I think this has to be taken for what it is. There's an inherent indication bias or confounding by indication that goes into allocating that therapy to patients who are perceived to have the potential to do well in the long-term. There may also be an expertise bias at the institutions that provide this and those patients may be receiving better secondary medical therapy or guidelines directed medical therapy, etc. So, maybe a halo effect that comes into play.

                                                In counterpart, the randomized control trials of which the latest was the arterial revascularization trial. Now available with data at 10 years, have shown essentially very little difference which regards to the use of multiple arterial grafts on long-term outcomes. Even looking at cardiac-specific outcomes like myocardial infarction. Actually the more compelling data came from their Radial Alliance, also led by Mario Gaudino who is the author of this, State of the Art paper.

                                                The conclusion of the article is that we need a trial and we need to include the radial artery. The answer may not necessarily lie with the use of mammary arteries, but it may be that the radial artery is more user friendly and more robust. So the new ROMA trial has been designed with that in mind. Comparing one arterial graft versus as many arterial grafts, as long as it's more than one in the test group that the surgeon wants to use. And the surgeon, she or he can use the right internal thoracic artery or radial artery in order to complete the revascularization.

                                                That trial is ongoing. Enrollment is on track and hopefully should provide answers to this very relevant question.

Dr James de Lemos:        You know that discussion about the limitations of clinical trials, Tim, I think leads really nicely into the frame of reference you received from Eugene Blackstone and Cleveland Clinic, doesn't it?

Dr Timothy Gardner:      Yeah, and it was really an article worth everybody reading. It's a short opinion piece and he points out the fact that we really have competing standards for choosing therapy. Sort of the standard traditional evidence based medicine, evidence-based medical care versus precision medicine which focuses on individual patients risk factors and so on. It's sort of the average treatment effect that we may be able to demonstrate well in randomized clinical trials versus real world experience with various therapies based on the risk profile of the patient. It's a really excellent article and as many of us know Gene Blackstone is a very thoughtful student of statistics in surgery and this is, I think, an excellent article. I'm really grateful for his doing this opinion piece for us.

Dr James de Lemos:        The last opinion piece we have is from Mike Farkouh in the group in Toronto. Can you just give the readers and listeners a bullet about what they might expect in that piece?

Dr Marc Ruel:                    I think it's one of the remaining big questions, if you will, in myocardial revascularization as to what should be done with diabetic patients in multi-vessel coronary artery disease who have an acute coronary syndrome and require revascularization. A very well written piece and certainly that instructs what probably the next five years we'll see in terms of big study questions in coronary REVASC.

Dr James de Lemos:        First I'd like to recognize Sarah O'Brien from the Circulation Editorial Office for her tremendous work for pulling this issue together. She's really the glue that brings this issue together every year and thank as well Marc, for your leadership again of this effort and Tim for your ongoing leadership at circulation with our cardiac content and vascular content as well as liaisoning with our surgical colleagues.

                                                Dr Marc, you get the last word. Can you please summarize the thoughts you'd like to leave our listeners with?

Dr Marc Ruel:                    Thank you, James, for your generous comments and also for your support of cardiovascular surgery in and of the team issue. I think again, we have a fantastic issue this year and we really want to gather the very best of cardiovascular surgery and we want to get the highest impact papers. Circulation is home for the best data, the best outcome, say the most interesting answers to important clinical questions that are around cardiovascular surgery.

                                                There's definitely an editorial desire to help with the best of cardiovascular surgery science. And I think I want to again launch a call to cardiac surgical investigators and cardiovascular and surgical investigators in general to consider circulation as your home.

Dr Timothy Gardner:      Yes. And if I could just add to that, not only are we interested in a surgery-themed issue annually that really highlights some of the best articles that we have to publish, but we also want some of the best surgery science during the course of the year. And just remind our surgeon colleagues that the particular advantage to having a paper published in circulation is the exposure of that study to a broad cardiovascular community. Not just surgeons, the predominant readership obviously of circulation, or cardiologists and other cardiovascular specialists. So that's the big advantage you get by having your best work published in circulation. We'd love to see more of it.

Dr Carolyn Lam:                This program is copyright American Heart Association 2019.