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Circulation on the Run


Oct 24, 2022

This week, please join Circulation's Associate Editor Marc Ruel and Executive Editor James de Lemos as they summarize all of the articles found in Circulation's annual Cardiovascular Surgery-Themed Issue for 2022.

Dr. James de Lemos:

Hi, welcome to Circulation on the Run. Greg and Carolyn are off today. My name is James de Lemos. I'm the executive editor for Circulation and I'm delighted to be joined today by Marc Ruel, who's the editor of our themed issue on cardiac surgery and leads the development and curation of all of the cardiac surgery content in Circulation. Marc, congratulations to you, to Mike Fischbein, to the whole Circ team on another spectacular effort to pull together this issue. Glad to have you here today.

Dr. Marc Ruel:

Well, thank you very much, James. It's really a team effort. I want to salute and thank the vision of Circulation to really give an important component to surgical science. As you often hear me say, your surgery provides the most durable and robust solution for advanced heart disease, right? So it's a very important part of the mission of Circulation as the premier cardiovascular journal. I want to thank you and also Joe Hill, our Editor-in-Chief and obviously the entire team of Circulation as well as all staff. Augie [Rivera], who is helping us on this call as well as Nick [Murphy] and many others who have made this issue possible.

Dr. James de Lemos:

Well, great. Well, let's get to this. And you recognize as well Mike Fischbein, who's the Cardiac Investor surgeon at Stanford who helps to edit the themed issue and really helps us to think about basic science into surgical specialties. Let me start, Marc, with cardiac bypass surgery. We have actually three papers in this issue that cover various aspects of CABG. The first one is one that you and I really resonated with, I know, because we talked about this. It's a paper by Ono from the SYNTAX Extended Survival study titled "Impact of Patient Reported and Pre-Procedural Physical and Mental Health on 10 year Mortality after PCI or CABG." And this is a really fascinating paper, looked at obviously patients with left main or multi vessels coronary disease, but used objective measures of physical and mental function from the SF-36 score and calculated summary physical and mental component scores.

And then used those scores to evaluate whether there were treatment interactions based on physical and mental performance metrics with regard to the benefit of CABG over PCI. And really fascinating, first that there was an interaction and that the magnitude of benefit of CABG over PCI for multi vessel disease was substantially greater among individuals that had higher physical performance as well as mental health performance. What did you think of this paper and data? I know you wrote a tremendous editorial to this. So this is something that you thought about as we were bringing the paper in, but also had to think about in terms of putting this paper in the context of this daily decision for patients with multi vessel disease.

Dr. Marc Ruel:

Thanks James. And I agree with you. I think this is a bit of a new paradigm, right, to really think of the individual patient decision. It's a form of precision medicine if you will, with regards in this case to physical functioning and mental functioning prior to something as invasive as undergoing CABG. So I want to thank you, the Circulation leadership for inviting Anne Williams who's a cardiologist and yours truly to write a tutorial on this piece because I do think you, that is really, it is something that's quite intriguing and it makes sense. I think it is intuitive. I think clinicians who send patients to CABG and see them come back and hopefully in a good state, the very vast majority of the time, do realize nevertheless that CABG is a very invasive procedure. So the patient has to be actively involved in her or his recovery.

And interestingly as you pointed out, there's quite a effect modification if you will, between the benefits of CABG over PCI in the SYNTAX trial, which many will remember as having randomized either left main or three vessel disease, coronary artery disease patients to PCI versus CABG. So there was an effect modification in those patients who had better functioning, not only physical, but interestingly, even more so mental component score of the SF-36 prior to operation. These patients would derive a greater benefit from having been randomized to CABG over PCI. So I think this is obviously logical, it makes sense and the converse will be true, but it's nice to see it formalized, to my knowledge, for the first time in the context of a rigorous randomized control trial such as SYNTAX with a long-term follow up.

Now obviously this, like any study, there are a few caveats. Not every single patient had their SF-36 at baseline, but roughly about 90 plus percent of patients did. And I think that is quite an important clinical lesson in terms of allocating PCI versus CBG... I've often said over the years as a division head and someone who performs this operation often to my more junior colleagues, "Don't perform bypass surgery if someone's not going to live five years." That might be a bit of a simplistic approach but the data and the conclusions from this paper would support that. It's probably not too farfetched to think as such.

Dr. James de Lemos:

I think that's a great point and your clinical experience is so valuable for us here. One question I have is, do you think that it would be advantageous to objectively measure these parameters or is this something that the heart team or the surgeon at the bedside can assess intuitively? Because I think that's the question, right? Is this something... It certainly fits with what we would expect intuitively, that the more complete and durable procedure works better in people that are more robust physically, mentally. But should we be measuring this preoperatively to help make that decision or should this be a intuitive decision by expert clinicians?

Dr. Marc Ruel:

It's a great question and I think it's one that's not yet answered. I mean, the data from the paper would suggest that it has to be a formalized physical component score and mental component score and then ready allocate according to turnstiles. But that being said, we all know that we can address those issues by an end of bed type of eyeball test, right? So I think you're absolutely right. It may be that a clinical expert may provide the same type of information. Unfortunately we don't have that from the paper but I think there will be several subsequent papers that will look at this.

I think we are in the era of precision medicine and one would even think, why has this not been done before considering how invasive bypass surgery is? You guys, you cardiologists and primary care physicians all know that it takes patients six to 12 months to be recover from sternal bypass surgery. Surgeons all be, I'll say that with a blink in my eye, don't always necessarily always see that, right? And think that's more like a one to three months but the data would suggest including that from randomized controlled trials such as Feedem, that it takes six to 12 months. So it's been one of my career long quest if you will, to make bypass surgery less invasive. And I think this type of paper really provides the impetus to do so.

Dr. James de Lemos:

Well, thanks. Let's shift gears from a study that makes perfect sense and fits our preconceived notions to maybe one that doesn't. And this is a research letter from a group led by Steve Goldman at University of Arizona looking at long term mortality from the VA study comparing radial arteries with saphenous vein conduits in CABG. And this looked at long term mortality from this study, which included over 700 individuals that had extended follow up beyond 10 years. At one year, the cath data had not shown differences in patency in this study, I think important to interpret, but they find absolutely no difference in mortality within similar median survival of 14 to 15 years after CABG in this study. This was controversial among the editors when we discussed it, but what are your thoughts about these data and how this informs the radial artery question in CABG?

Dr. Marc Ruel:

Absolutely. You are so right in seeing that this was controversial because there are in fact two ways to look at this paper, right? You can drain the information that's in there or you can be a naysayer. And there's credence to both approaches, in my opinion. One could say, "Well, there was no difference at one year in terms of graph patency, so why would there be one at 14-15 years?" Well, the answer to that would be the durability of the compared conduits would be potentially different, right? One to five years is what we call the "golden age of saphenous vein grafts." And beyond that time period, one could perhaps expect that the radial artery would do better and start translating into clinical benefits. But that was not seen in this long-term analysis of the VA RCT that compared the use of a saphenous vein versus a radial artery.

The other way to perhaps find why the data is discrepant versus the methodology that had been performed before showing an advantage for the radial artery, would be that this is more perhaps of a real world type of experience. It comes from VA centers. Perhaps the expertise or the level of penetrance if you will, of use of the radial artery was not the same as other centers that maybe more "academic" and more vested into using the radial. So it's possible that those could have played a difference in nullifying if you will, the results of radial artery. But I nevertheless think that it's very important data. It makes us think and it is the largest single series data available that compares the radial to saphenous vein in a randomized control setting. So one cannot ignore it, and I think it's a very important piece of information that strengthens the surgery themed dish.

Dr. James de Lemos:

Thank you, Marc. And then the last CABG related article that I'd like to talk about is the prospective piece by Mario Gaudino and Bruce Lytle discussing the right internal thoracic artery for bypass. Asking the question, did we get it wrong? And this is really a very interesting piece. I encourage our readers to look at. That attempts really to reconcile the strong promise of the RITA with the disappointing results from art and the higher than expected failure rates in other trials. And what the authors do here really resonates with, Marc some of your points about individualizing treatment.

They point out that some of the worse than expected RITA results may reflect the artery to which the RITA has been anecimosed, simply that results when an anecimosed to non-LED targets aren't as good and potentially the experience of the operators. Their final conclusion really isn't that, the reader's not a superior conduit but that perhaps more individualization, both at the patient level but also based on physician experience, maybe what's needed to achieve the optimal selection of conduits and bypass results. What did you think of this? How did their conclusions and interpretation resonate with you?

Dr. Marc Ruel:

I agree with your summary James and I think you are spot on. What's interesting in addition from this frame of reference is that it unites the opinions of two key opinion leaders, i.e Mario Gaudino, who's essentially behind much of the data favoring the radial artery over the use of the saphenous vein. And Bruce Lytle, who historically was behind really proposing the use of the right internal thoracic artery and this bilateral ITA grafting if you will, and they are really coming together and putting their thoughts in a really sensible manner with regards to the points that you raised already. I would add in my own opinion, it's twofold. One, there's nothing biologically wrong with the right internal thoracic artery. So if the LITA works, the RITA should work as well from a biologic point of view. In fact, surgeons know that it's often bigger than the left internal thoracic artery and even more suitable or suited as account with.

What might be wrong is the applicability of it and that question really goes in a couple of important manners. Let's remember surgery is a craft, right? And it's a bit different. It's something I like to repeat, and it's not always captured. It's not really a pure science, like for instance, giving atorvastatin 40 milligrams would be this much more variability. And if you allow me a ten second example, if you were to take one of the bronze tools from Rodin, a grape sculptures, and take it away from him, the sculptures would not be as good. But if you were to give that tool to all semi-professional sculptures around the globe, the United States or France for instance, you may not see any benefit from that tool. So again, the crafty example of surgery is something that we have to compose with all the time.

So the RITA is a great conduit, but it's often not onto the LED per se. And we know that LED in an average patient, which doesn't exist, it's probably about 50% of the left heart profusion. So really the LITA has an advantage from that point of view. And when we compare studies that have used the RITA on a non LED target, there are in some cases bound to fail or at least be neutral. So I think the jury's still out but really the perspective that's denoted here, as you said, is a fascinating one coming from two key opinion leaders, each in their camp of radial versus right internal thoracic artery use.

Dr. James de Lemos:

Well, fabulous discussion, Marc. I really appreciate your insights. I think as cardiologists, the decision making about conduits can often be opaque, and this is really insightful. Let's switch gears and talk about valve surgery. We have two papers on valve surgery. First, an original research article by Johan Wedin from Uppsala on bicuspid aortic stenosis demonstrating adverse ventricular remodeling and impaired cardiac function prior to surgery with a heightened risk of postoperative heart failure. This is a really interesting study that looked at 271 patients that were undergoing surgical aortic valve replacement.

About half with bicuspid valves and half with tricuspid aortic valves, and they did comprehensive preoperative echo-cardiography and then followed the patients for four to five years after followup. And despite the expected finding that the bicuspid patients for younger, they had a substantially worse LV echo parameters pre-op with greater LV wall fitness, greater LV mass, worse preoperative LV function. And that translated even after successful AVR into increased risks for postoperative heart failure hospitalizations when compared to individuals with tricuspid aortic valves. And so the authors conclude that at least in contemporary practice, perhaps individuals are undergoing surgery for bicuspid aortic valve stenosis relatively later in the natural history, and they might merit closer civilians and possibly earlier intervention. What did you think of these data and do they make you think about your timing of recommendation for surgery with bicuspid aortic stenosis?

Dr. Marc Ruel:

Absolutely, and thank you James. I think this is very much in line with the current precision medicine led trends of operating earlier on patients with aortic stenosis. I think this is another subgroup that really deserves our attention. I think there are two things at play here with regards to patients who would have a comparable degree of hemodynamic aortic stenosis, either coming from a bicuspid aortic valve phenotype versus a normal tricuspid aortic valve phenotype. And I think the two important differences are, first, often the bicuspid valves are more prone to have a mixed disease and being more calcified as well. We often see surgery, what I call these black valves, like the valve is so calcified and necrotic that it actually turns black or navy blue in color. And this is not an uncommon finding in younger patients typically than tricuspid aortic valve patients.

The second thing is that we have to remember that bicuspid aortic valve disease is a lifelong illness. So these patients often go undetected for a very long time. They may be 55 years old compared to someone who's 68 and have the same degree of hemodynamic aortic stenosis and even AI. But the disease has really, in the bicuspid aortic valve patient, has probably been there for decades, sometimes even the whole life. So I think the effects on the left ventricle are destined to be worse, and also in terms of recovery after resection and after aortic valve replacement. So I think these are humbling tidbits that come from this paper that really even allow us in this era of early TAVR and now two randomized trials that have looked... One from Europe and one from Korea that have looked at asymptomatic aortic valve replacement interventions with favorable results towards early intervention. That really tell us that we should pay even closer attention to those patients with bicuspid aortic valve phenotypes.

Dr. James de Lemos:

Thanks, Marc.

And the second valve related paper is a prospective piece by [Rebecca] Becky Hahn, Vincent Chan and David Adams, evaluating current indications for a transcatheter edged edge repair of the mitral valve for primary mitral regurgitation. I thought this was a really well done piece and one that I appreciated focus specifically on primary micro-regurgitation. The piece includes a terrific algorithm for clinicians that really helps to guide decision making through a multidisciplinary approach.

They talk about the importance of specialized valve imagers, given the complexity of evaluating even the etiology of micro-regurgitation. The importance of excellence in determining the quantitation of severe MR, valve morphology and dimensions. And then really take it a step further to drive decision makings based on risk assessment of the patient. Obviously for primary MR for adequate surgical risk patients surgery is recommended, but then it walks through the decision making for which of the patients that are not surgical candidates might be optimal candidates for transcatheter techniques. How do you think this field's moving and how did this perspective change your thinking?

Dr. Marc Ruel:

This is such an excellent piece as you denoted. I think it really comes from three experts in the field representing different school of thoughts, if you will. One, more hybrid, more catheter based and more surgery based. And I think the jury's still out on transcatheter edge to edge repair, especially for primary marginal regurgitation. It's paradoxical as we're hoping that edge to edge repair would be primarily used in secondary MR and have great results. We now know and somewhat humbling, that it works not as great as we were hoping for secondary MR and it seems to be working pretty well where we already had a fantastic surgical therapy for it, which is essentially primary MR and Fibroelastic Deficiency type of lesions. Now, as you know, these patients do extremely well with surgery. There are several series of 800, 900, a thousand patients operated either conventionally or minimal invasively with maybe one death. Still one too much I would argue, but extremely low risks.

These are the healthiest patients that a cardiac surgeon often can operate because I would argue this probably an inverse correlation with coronary artery and peripheral vascular disease in those patients. It's hard to know. There's some elements of the answer that we don't have yet. What about the very long term follow up? What about 10 years? What happens when an edge to edge repair fails and it was for primary MR in a younger patient?

And I think the authors really captured those very important caveats quite elegantly and provide a very balanced view. So like you, I'm very happy with this piece. Lastly, I'll conclude by saying there's even controversy as to sub-clinical parameters with edge to edge versus surgical mitral valve pair for primary MR. What does two plus mitral regurgitation that is post-procedure, What does that mean? Is this something that's going to impact the patient at 10 years, at 20 years and perhaps churn, what was it initially, a great therapeutic solution into one that's not so desirable? So again, as I said, the jury's still out on this and I think these really captures the main element of the answer as we know them in 2022.

Dr. James de Lemos:

Excellent points. I think really, I love your conclusion that hopefully there will be a better transcatheter solution than this for patients that aren't surgical candidates, obviously, because it doesn't, unlike TAVR, this doesn't come close to matching the surgical option. The last couple of papers in the issue focus on putting cardiac surgery in the greater context of the patient experience and the healthcare system experience and are in the health services research phase. The first one is from multi-centered team led by Amgad Mentias at Cleveland Clinic and Ambarish Pandey at UT Southwestern. And it focuses on a new performance metric that they're calling, 90 day risk standardized home time for cardiac surgery hospitals in the US.

And this group has done several studies with this new metric that basically is attempting to evaluate performance at the patient level with a very patient-centric metric of how much time they spend at home. They've published previously using data from heart failure patients and post MI patients and now are extending this to cardiac surgery and using risk adjustment of time outside the hospital in the 90 days after surgery to evaluate the variability among cardiac surgical programs. And they find that the metric correlates with mortality and readmission, that higher volume surgical centers are associated with more time spent out of the hospital.

And then when they compare it more directly with approaches that are used to currently rank performance, they see that this results in some reclassification of performance categories versus the other metrics. It's early in the life of this new metric but I'm interested to see intuitively is a cardiac surgeon, how does another tool to evaluate your performance, your team's performance and your hospital's performance resonate? And does this have any intrinsic advantages to you over the other risk standardized tools that are currently being used? Certainly in the US I don't know what's happening in Canada.

Dr. Marc Ruel:

Great points, James and I agree, this is an impressive data set. It's almost on 1 million patients from more than 1000 centers in the US. And as you said, it is a new patient based metric. It's a bit of a patient before the outcome if you will, those PROs that are so more commonly now the object of research with regards to outcomes. I would somewhat simplistically say that there are three possible outcomes to any heart surgery, patient survives and feels better. That's number one, that's what we want to achieve for everybody. Unfortunately, there are two other outcomes that can happen. Patient survives but patient is not improved by the surgery or has a complication as a result of it and quality of life does not improve. And third, obviously the one that is the obvious, highly detrimental is that patient does not make it from the surgery.

But I think really what this paper highlights is the importance of really focusing on the first one by the number of days spent at home during the first 90 days post intervention, post-surgery itself. So I think it is really a marker of how well the patient's doing. It closes the loop, if you will, with the first paper that we looked at, in an observational large data set type of way. But it again calls to, how was the patient functioning pre-op? And that data, as we know, is not available from this series. So it could be three things essentially. It could be performance and definitely it pleases the mind to think that the performance of the institution i.e, the quality of the care provided has a huge impact. But it could also be two other things.

It could be the level of functioning of the patient. The ability to get back and spend many of those first 90 days at home versus not, of the patient himself or herself, depending on the various populations that are served by those institutions. And third, it could also be a little bit of a recurrent theme of mine and I apologize for that, but it could be the degree of invasiveness that's provided if you out of surgeries offered to these patients. So I think these are interesting paradigms. They are very important. Again, they're completely in line with precision medicine and I think that this performance measure, as you alluded to, is an important point because a patient who survives but doesn't go back home really is not deriving a benefit from any operation.

Dr. James de Lemos:

Yeah, great points. And I think this discussion really leads us into our discussion, the last paper, which is another paper that attempts to put surgery in the greater context of the population and environment in which patients come. And this is led by Aditya Sengupta and her team from Boston Children's Hospital evaluating contemporary socioeconomic and childhood opportunity disparities in congenital heart surgery. This is a really next level analysis of associations between socioeconomic status and outcomes after congenital heart disease surgery in children focusing in one high volume quaternary center in Boston. And what they did is developed a novel predictor that was a US census tract based nationally normed composite metric of contemporary childhood, what they called neighborhood opportunity. And this comprised 29 indicators across three domains.

The three domains were education, health, and environment and socioeconomic domains. And they classified the patients into very low, low, moderate, high and very high neighborhood opportunity. And then they looked at evaluations across multiple outcomes. They did not see any association of neighborhood opportunity with early deaths, which I think is encouraging, but they did see that children with lower neighborhood opportunity had longer length of stay, higher healthcare costs and then significantly higher late deaths following surgery when the multiple components of long term care of these children probably have time to operationalize. I found this sobering and a complex message that excellent cardiac surgery can deliver superb outcomes across all levels of opportunity but if these issues aren't addressed, there are financial implications, but more importantly, the long term benefits of the cardiac surgical procedures aren't fully realized. Interested to hear your thoughts on this and how this might apply more broadly even to adult surgery.

Dr. Marc Ruel:

I agree, James and I too, really love this paper. As you say, it is sobering. It's a paper for physicians, but I would argue it's probably bedtime reading for Mr. Biden, any other country leaders as well. Whether it's Mr. Macron or Mr. Trudeau. Definitely something that is shows that what happens after the hospital stay, even in something as complex as congenital heart surgery, performed at Boston children, obviously a great institution. But what is shown here is that the institution with its top quality outcomes as we know them to be, is a fantastic societal and outcome equalizer, if you will. But once that passage through the tertiary or coronary institution has occurred, then reality sets in. And the childhood opportunity index that the authors had previously published in JAMA proves to be, again, a very important predictor of how these kids do later on. So this refers really to the societal contract that we're all part of as physicians. And we obviously, a big part of our mission is to improve the outcomes in hospital, but also beyond it. And I think this paper illustrates this very nicely as you so eloquently summarized.

Dr. James de Lemos:

Well, thanks. And I'll just, before I hand it over to you to conclude and wrap up, just compliment you and Mike and the entire team, as well as the authors who have submitted not just these but so many other superb papers covering the full spectrum of surgical sciences Circulation. I'm proud for us to have the opportunity to share these terrific papers with our readers and with researchers. And congratulations again to you for pulling this together.

Dr. Marc Ruel:

Well, you're very kind and thank you, James. To you and Joe, Darren and our and entire editorial leadership for the important place given to surgery within Circulation. It's something that I believe is important and resonates with surgeons but also non-surgeons who are part of the greater cardiovascular community. So it's tremendously important and we're very thankful for that opportunity.

Dr. James de Lemos:

Well, I'd like to thank all our listeners for joining us today and remind you to tune in next week when Greg and Carolyn will be back for their regularly scheduled podcast.

Dr. Greg Hundley:

This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.