Circulation October 25, 2016 Issue

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Carolyn: 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. We have such a special podcast for you today. The entire podcast is going to be a conversation with two very special guests, Dr. Marc Ruel from The University of Ottawa Heart Institute, the guest editor of the surgery themed issue this week. Hi Marc.

Marc: Hello Carolyn. How are you?

Carolyn: Very good. Especially because we also have Dr. Timothy Gardner, Surgeon, Associate Editor from Christiana Care Health System. Welcome back again, Tim.

Timothy: Thank you, Carolyn. Glad to be here.

Carolyn: Marc, could you first give us an overview of the surgery themed issue from your perspective.

Marc: This year as we have had on previous years, we are having a surgery themed issue which comprises what I would argue which is some of the very best cardiac surgical science can offer to the wide readership in the cardiovascular community that served by circulation. This year, we will have a total of ten articles that would be published in circulation, as a section of one of our regular issues and out of those ten, there are five original papers. There's one research letter which is an original research article but in a shorter format and we'll also have one invited perspective paper namely about coronary artery bypass grafting and its future with respect to multi-arterial grafts and the themed issue will be completed by three state of the art papers that deal in a very in depth comprehensive way with some important problems that the cardiovascular community faces from a clinical point of view.

Carolyn: Thanks Marc. That was a beautiful summary of the issue. I couldn't help but notice that there was a theme of coronary artery bypass surgery covering at least four of the papers and I really like your thoughts on that. You covered everything from medical therapy, CABG versus PCI, on versus off-pump, emergency surgery in the setting of shock. Could you go through each of these four papers a little and tell us what was your take home message from each?

Marc: As you said, there are three original research articles and one invited perspective that relate to coronary artery bypass grafting surgery and these encompass the number of clinical problems that are still controversial and certainly I believe they contribute a very, very significant [inaudible 00:02:31] with the wealth of knowledge that the cardiovascular community is looking for at this point. If I may go one by one, just with a very high level overview, if you will. The first one is a paper from the Leipzig Heart Center with first author, [Pieroz Adewalla 00:02:45], which looked at surgery for acute myocardial infarction but accompanied with cardiogenic shock. As you know, many patients undergo surgery in an acute MI context, but surgery for cardiogenic shock is often a very gruesome difficult decision.

Leipzig Heart Center looked at over 3,000 patients who had an acute MI prior to cardiac surgery for bypass surgery and of these, there were 508 patients who actually had cardiogenic shock due to [valve 00:03:15] failure with myocardial dysfunction and to give you an idea, these patients were quite sick. There's about 40% of the patients who were ventilated prior to surgery or very close to 40%. The timing was quite urgent, those patients were on inotrophes and on vasopressors to support their blood pressure prior to operation. Essentially, what they found is that first the outcomes got better over the last number of years, this is a series that dates back to about the 2000's, so the early 2000's.

They also favor an approach where they tried to avoid a cardioplegic arrest of the heart. Their favored overall approach is to do what we call on-pump beating heart type of surgery which would be a surgery where the cardioplegia would not be administered to stop the heart but the hemodynamics would be supported for the cardio coronary bypass. They also have over the years since the beginning of this year, is in 2000 ranging up to 2014 of increasing the use of the off-pump bypass surgery and certainly the outcomes have been better and the mortality although high has decreased significantly. It was as high as 40% in the early parts of the cohort if you will and in the latest third of the experience, therefore from 2010 to 2014, the mortality has been down to about 25%.

Again, these are patients who present with cardiogenic shock. What's also interesting to note is that patients who survive out of hospital still have a significant mortality burden and about 50% of them survive long term. What was interesting is the Leipzig group is looking at some predictors of bad outcomes in those patients and they found that the serum lactate over four minimal per liter was actually a very robust and multi-variative predictor of a poor outcome after surgery.

Carolyn: That was a great summary of that first paper. You mentioned beating heart surgery and so on. Would you like to comment on next paper that I think was the largest single institution European study comparing on versus off-pump bypass surgery?

Marc: You're absolutely right. This is a paper from England, [inaudible 00:05:25] from Liverpool, where the patients were gathered from and with some contribution from Oxford as well from a statistical and methodological point of view and it's a retrospective cohort study of all isolated CABG patients in Liverpool between 2001 and 2015. These are bypass surgery patients and in total, there were over 13,000 patients who had CABG. About 6,000 patients had off CAB which is off-pump bypass surgery and more than 7,000 had bypass with cardiopulmonary bypass. The median follow up was 6.2 years. What's interesting in this paper is that they essentially found equivalent long term outcomes. As you know, there has been some debate regarding the completions of myocardial revascularization and the long term graft patency with off-pump surgery versus on-pump surgery. Also named conventional CABG.

What's interesting here is that the benefits of off-pump CABG appear to be seen early on with regards to antiemetic release as stroke rates, etc. Which does correspond to some of what has seen in the randomized controlled studies. However, the long term data is interesting. There's a a nice editorial about this paper written from a group from the Cleveland Clinic with Dr. Joe Sabik as the senior author and essentially it raised a number of good points, although this is an important series, it also shows that the surgeons who are very good at off-pump bypass surgery may overall be slightly technically more skilled at doing bypass surgery in itself and for instance, use more often arterial grafts and have more advanced techniques in their completion of bypass surgeries for their patients.

Carolyn: Right. I'm so glad you mentioned the editorial. I was about to bring that up as well. Switching gears to you very kindly included a paper that talked about medications and the impact of here is the medical therapy on the comparative outcomes between CABG and PCI. Would you like to discuss that paper?

Marc: This is a paper from the Care Registry which has generated some interesting publications in the past. The lead author is Dr. Paul Polinski and there's co-authors, Dr. Herbert Prince and Michael Mack from Dallas as well. This was presented at the science sessions in Orlando last November and it's an interesting paper. Essentially they have looked at large databases, again the Care Registry which comprises eight community hospitals and they look at six month period of performance of CABG and those eight community hospitals. They ended up with over 2,700 patients who were then systematically followed on a regular basis up to 2009 at which time the database was locked.

They look at various outcomes but also medication use in great detail over that period of time and the interesting perspective that this paper brings is that first, most patients at least in that period were not on optimal medical therapy. The authors used their own predefined definitions of what constitutes optimal medical therapy and this is with regards to adherence to aspirin use, lipid lowering agents, beta blockers and indicates of PCI, dual anti-platelet therapy. As expected but nicely documented in this paper, the outcomes of patients who were not on optimal medical therapy were much worse than those who were and CABG proved to be more robust in patients who were not on optimal medical therapy compared to PCI.

The differences between CABG and PCI in patients who were on optimal medical therapy tended to vanish. However, a number of caveats here is that only 25% of patients in fact in this cohort were on optimal medical therapy. The vast majority of patients were not considered to be on optimal medical therapy. Therefore, there are considerations of definitions that one has to be aware of and also considerations of statistical power because the group that was on optimal medical therapy was much smaller than the other group. Therefore, the effects, the superiority of CABG over PCI could only be firmly demonstrated in the group was not on optimal therapy, again comprising 75% of patients in this cohort.

Carolyn: I love your summaries and they really show that these are true significant original contributions to that knowledge gaps in coronary artery bypass surgery. To round it all up, you also invited a perspective on novel concepts. Would you like to comment on that paper?

Marc: This is an invited perspective in the view classifications that circulation has which is entitled, "The evolution of coronary bypass surgery will determine relevance as a standard of care for the treatment of multi-vessel CABG." It is authored by three leaders in the field, Dr. Gener, Dr. Gudino, and Dr. Grouw. Dr. Gener has been leading several of what I would call the advanced multi-vessel coronary re-vascularization trials looking for instance at multi-arterial grafts doing numerous anastomosis with two ventral mammary arteries in a wide fashion. He's been a leader of this movement certainly. Dr. Gudino recently published [inaudible 00:10:43] the 20 years of outcome of the radial artery graft and certainly has been one of the pioneers which use of this arterial graft for coronary artery bypass surgery. What the authors provide here is a very nice summary of what the trials have shown so far and they also report as many know that their rate of multi-arterial grafts use in SYNTAX, FREEDOM and I think we will soon see in EXCEL and NOBLE that will be presented this fall, has not been as high as it should have been.

In the US, it is estimated right now that the rate of use of more than one mammary artery is less than 10% across the nation, and other countries have not performed better than this either. This perspective is a call to improving the quality of multi-vessel coronary artery bypass mainly through the use of multiple arterial re-vascularization. There is also considerations around the hybrid coronary re-vascularization and as well as the use of off-pump versus on-pump surgery.

Carolyn: I am really proud and privileged to have helped to manage one of the papers as associate editors in this issue as well and that is the paper from the group with corresponding author, Dr. Veselik, from Boston Children's Hospital and it centers around patients with congenitally corrected transposition of the great arteries but a management problem that is really increasingly encountered and really needs to be reviewed properly and that is the management of systemic right ventricular failure in these patients. Tim, you were so helpful in looking at this paper as well. Could you share some of your thoughts?

Timothy: Well, this is a somewhat unique situation where a patient with this condition, congenitally corrected transposition of the great arteries may go through early life, in fact may end up as a young adult before this particular condition is identified because if there is no shunting or no cause for cyanosis and heart murmurs and so on early on, the circulations seem to work pretty well until the poorly prepared right ventricle which is the systemic ventricle, starts to fail after years of work carrying the systemic circulation and that is really the focus of the paper. There's been a lot of work and publications and attention to transposition syndromes but this particular one is a condition that may be first encountered by adult heart failure cardiologist who have not had this kind of exposure to congenital heart disease. It's a particularly apt paper to bring this condition to our attention and to demonstrate that really it's the adult heart failure cardiologist who may be managing these patients in their late 20's or 30's, when that systemic right ventricle fails because of a lack of formation to manage the systemic circulation.

Carolyn: Exactly. Written by a group that has one of the most robust experiences in this field, so that also brings to mind another state of the art article in the issue that refers to the hypoplastic left heart syndrome and though it's entitled that and people may think it's rare, I think it's increasingly being seen in the adult cardiology world as well. You want to comment on that one?

Timothy: That actually is one of the main points of this paper that this very, very difficult condition of hypoplastic left heart syndrome that requires staged operations beginning in the neonatal period has now reached the state of surgical accomplishment in medical management where many of these young children are surviving into young adulthood. Albeit, with having had two, or three, or four operations. In a community like ours here in Delaware, where pediatric patients transition to adult services and adult cardiologist sometime around their 20's, it's really important for the entire cardiology community to be aware of what has happened in terms of the successful staged treatment of children with hypoplastic left heart syndrome and that is brought out very nicely by the three authors who look at various accomplishments and different techniques for managing these staged repairs. It is very amazing to someone who has been observing this field for sometime as I have, that many of these children are in fact surviving into young adulthood and will require comprehensive cardiovascular treatment, not just by neonatal specialist but by specialist in adult congenital heart disease.

Carolyn: Exactly, which is why such a timely state of the art articles both of them for this issue. There is another state of the art article that you were handling, Tim, "The Surgical Management of Infective Endocarditis Complicated by Embolic Stroke", now that's an important topic.

Timothy: Absolutely, as we know up to a half or more of patients with infective endocarditis primarily on their left sided heart valves will have cerebral embolic problems and it has really been a dilemma for many of us in terms of optimal timing for the cardiac surgery with respect to the existence of cerebral injury from the embolism, from hemorrhage that may occur, from hemorrhage that may be exacerbated by placing the patient on the heart-lung machine, etc, and this paper really takes an extremely comprehensive, careful and judicious look at all of the evidence that has emerged and it has been a confusing field of evidence as to how to best optimally manage these patients with cerebral involvement from infective endocarditis.

I think this paper is going to have a big impact. It appears that there are a couple of messages that I took away from this paper. Number one, we really need to use the full panoply of diagnostic opportunities or diagnostic test for characterizing the nature and the extent of the cerebral involvement in these patients and then perhaps even more important, we need to convene what the authors called the infective endocarditis team and that has to include not just the surgeon, the cardiologist and the infectious disease specialist but also the neurologist, the neuro-interventional specialist, the neurosurgeon and so on because all of these specialist need to contribute to the assessment and choosing the optimal timing for these patients.

That is the central message of the paper. The authors also suggest that we may be getting to the point where we need to update and make sure that the guidelines that we're using are in fact current. Current in the sense that the experience now with advance imaging and with more aggressive management of the neurological or cerebral issues really need to be factored into how best to handle these patients, but I think this paper is going to have a big impact, it's very well written and very thorough.

Carolyn: I agree. In fact all the content we just discussed is just so rich. Congratulations on such a beautiful issue. Marc, do you have any last highlights you'd like our audience to hear about?

Marc: I'd like to also mention two other original research papers that will be featured in the surgery themed issue. One, in keeping with the congenital theme that we had talked about is about the modified [Straun's 00:19:08] procedure for palliation of severe Ebstein's anomaly and this is a series actually from Professor [Straun 00:19:16] himself mostly originating from Children's Hospital Los Angeles and essentially, the series here is that of 27 patients about equal in gender distribution who were operated at seven days of life, between 1989 and 2015.

It's very interesting that patients did well, the survival at ten years is 76% and most of them have undergone successful Fontan completion. I think this is a very important paper not only because it is an extremely vexing and difficult problem to deal with Esbtein's anomaly but it comes from the innovator of the operation himself with his team and it provides much needed data regarding the long term outcomes of these children with this very difficult solution. I think this will be of great interest and also as we commented before veering into the world of adult cardiology as well, because fortunately most of these patients survive into adulthood.

The other paper I wanted to touch upon which is also an original research paper that will be in this themed issue, is a paper from the CTSN Group looking at the impact of left ventricular to mitral valve are being mismatched on recurrent ischemic MR after ring annuloplasty and this paper used the free innovative and interesting methods. As some of you may know, there were two large files recently that were conducted by the CTSN looking at either moderate MR at the time of coronary artery bypass grafting or at severe ischemic mitral regurgitation. The randomizations were different when the moderate MR was CABG lone versus CABG post mitral valve repair and the severe MR was mitral valve repair versus mitral valve replacement.

These studies have led to interesting conclusions that several will know about but what's been interesting in the current study is that they have gathered all patients who underwent mitral valve repair from both studies, original randomized trials and they ended up with about 214 patients who underwent mitral valve repair. The others had moderate or severe MR and basically the point of this study is to look at predictors of failure of mitral valve repair and this is an extremely relevant problem, not only for the cardiac surgical community I would venture, but also for heart failure community and for JV General cardiology community. What the others found is that the most important predictor of recurrent mitral regurgitation after mitral valve repair was something called the left ventricular and systolic diameter to ring size ratio and they provide an algorithm which will have to be tested clinically with regards to whether it is applicable and indeed changes outcome, but this is a very important discovery in the field of ischemic MR and enabling us to hopefully better understand and improve outcomes for patients with this very difficult problem.

Carolyn: I agree. Thank you so much, Marc and Tim for this most insightful discussion. Thank you very much and to the listeners out there, don't forget you've been listening to Circulation on the Run. Join us next next week for more highlights and features.

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