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Circulation on the Run

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Aug 1, 2016

Carolyn:
Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm doctor Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Joining on me in just a moment are two guests to discuss a very exciting new category of papers, known as the white paper. The topic for today is an evolution within the field of current day percutaneous coronary intervention that of the treatment of higher risk patients with an indication for revascularization. But first, here is your summary of this week's journal.

 
 
The first study is from first author doctor Jolis and corresponding author doctor Grainger, from the duke clinical research institute in Durham, North Carolina. These authors describe the American Heart Association Mission: Lifeline, STEMI Systems Accelerator. This exciting project represents the largest effort ever attempted in the United States to organize ST segment elevation myocardial infarction care across multiple regions, including 484 hospitals, 1,253 emergency medical services across sixteen regions and involving more than 23,800 patients.

 
 
Indeed, this project aims to organize coordinated regional reperfusion plans so as to increase the proportion of patients treated within guideline goals, that is a first medical contact to devise time of less than 90 minutes for STEMI patients directly presenting to PCI capable hospitals and less than 120 minutes for transferred patients.

 
 
The authors observed that during the study period of July 2012 to December 2013, there was a significant increase in the proportion of patients meeting these guideline goals, including an increase from 50% to 55% of STEMI patients directly presenting via emergency services and from 44% to 48% of those transfer patients. The authors concluded that these improvements, while modest, suggest the potential for reductions in total ischemic time and happily observe corresponding trends towards lower in-hospital mortality compared with the national data towards the end of the measurement period. Indeed, the tickle message is that the findings support continued efforts to implement regional STEMI networks.

 
 
The next study is by first author doctor Hidari and corresponding author doctor Kuang from the Brigham and Women's Hospital in Boston, Massachusetts. They describe the OMEGA-REMODEL randomized clinical trial. This is a multi-center, double-blinded, placebo control trial of 358 participants presenting within acute myocardial infarction who are randomized to six months of high dose omega-3 fatty acids at four grams daily versus placebo.

 
 
Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and following therapy with the primary study in point being a change in left ventricular systolic volume index. Indeed, the authors reported that compared to placebo, patients who received four grams daily omega-3 fatty acids experienced significant improvements in both left ventricular and systolic volume and surrogate measures of non-infarct myocardial fibrosis during the six months of treatment.

 
 
These remodeling benefits further followed a dose response relationship with the rise in the in vivo omega-3 fatty acid levels as quantified by your red blood cell index. They concluded that four grams daily of omega-3 fatty acid is a safe and effective treatment in improving cardiac remodeling in patients receiving current guideline based post-myocardial infarction therapies. Indeed, this does warrant perspective clinical studies.

 
 
The third study is by first author doctor Liu and corresponding author doctor Sia from University of Texas, Houston Medical School and Colleagues, who sought to understand the molecular basis underlying adaption to high altitude hypoxia. By conducting both human high altitude and most genetic studies, the authors identified a novel functional role of CD73-dependent elevations in extracellular adenosin signolin in response to high altitude hypoxia.

 
 
This led to sequential activation of a readthrough site AMP-activated protein kinase, which in turn resulted in increased 2,3-bisphosphoglyceric production and enhanced oxygen release capacity to peripheral tissues. Thus, reducing tissue hypoxia, inflammation and pulmonary injury. These findings have significantly added to our understanding of the molecular mechanisms underlying adaption to hypoxia. Thereby, opened novel therapeutic possibilities for the prevention and treatment of hypoxia related conditions.

 
 
The final study is from first author doctor Yen and corresponding author doctor Chen from the National Taiwan University and Colleagues, who aimed to determine the effect of betel nut chewing and paternal smoking on the risks of early metabolic syndrome in human offspring. The author studied more than 13,000 parent-child trios identified from more than 238,000 Taiwanese aged 20 years or older screened in two large community based screening cohorts.

 
 
The main finding was that pre-fatherhood habits of both betel nut chewing and cigarette smoking led to a 77% and 27% increase in risk of early metabolic syndrome in their offspring respectively. In fact, they even observed a dose-response relationship where the risk was higher with an increase in duration of exposure as well as with earlier age of starting exposure. These findings interestingly suggest that genetic or epigenetic changes due to exposure to both betel nut and cigarette smoking before birth can contribute to early occurrence of metabolic syndrome in offspring. In fact, these findings really support education for avoidance of these habits or cessation of these habits.

 
 
That was your weekly summary. Now, for our feature paper. Our feature paper this week is a white paper regarding the treatment of higher risk patients with an indication for revascularization and evolution within the field current-day percutaneous coronary intervention. To join me in this discussion, I'll have the first and corresponding author doctor Ajay Kirtane from Colombia University Medical Center, New York Presbyterian hospital, as well as doctor [Manus Brelaques 00:08:22], associate editor from UT Southwestern. Welcome, Ajay and Manus.

 
Ajay:
Thanks so much for having us.

 
Manus:
Thanks Carolyn.

 
Carolyn:
Great. Manus, I would love if we could start by talking about the concept of the white paper and what circulation is looking in these white papers.

 
Manus:
Of course. It is a very exciting part of the new circulation which is for topics that are very timely and important, but at the same time there's not enough populous data and populous literature to be able to address it in a more formal systematic review way. The concept is that establish the leaders in the field. I'm going to provide their perspectives which have derived through their clinical practice and be able to inform us of what the current issues are, how can they best be addressed and what are the next steps forward.

 
Carolyn:
That's great, and what a great example to start with with this paper by Ajay. Ajay, maybe I could just start by asking you to make it crystal clear to us the kind of patients you're referring to in this higher risk and the context and the scope of the problem that you're talking about in your paper.

 
Ajay:
Absolutely. First of all, I'm honored that you would consider that's both timely and important and that this will be one of the new papers in the series on behalf of all the [cohorts 00:09:44] is we're really pleased to be able to discuss it. I think the reason that we find this really critical at this juncture is because what we're sort of saying is an evolution in current-day [catlab 00:09:53] practice. There are many patients now who were seen that have either been turned down for cardiac surgery of have highly complex disease that we know merit revascularization.

 
 
In other words, medical therapy has failed for them either from the symptomatic standpoint or because it puts them at too high risk given the complexity of their coronary anatomy and where these lesions are located. Yet at the same time, in order to be able to treat these patients effectively, we need to grasp not only advanced techniques in terms of how to do it, but also need to be able to select the patients appropriately so that they can undergo these procedures safely and to drag the benefit that we'd like to be able to offer them.

 
 
Just one brief thing to mention is that we certainly know that over the past 10 years or so, there's been a lot of criticism of the PCI procedures they could perform, particularly here in the United states. Some of them were perhaps unnecessary or some of them were not necessarily benefiting patients. The good news is we've curtailed a lot of that, but yet at the same with that curtail we've sort of seen a decline in these types of cases that we refer to in the paper where patients really could benefit from revascularization, but for whatever reason or not being offered it.

 
Carolyn:
Listeners might be wondering though, what is the difference between what you're talking about high risk, and we read a lot of papers about complex procedures and complex PCI, you want to make that differentiation just slightly clearer?

 
Ajay:
Sure. I think that complex PCI has been something that carries the historical definition and usually involves lesion subsets like the left main, chronic total occlusion, bifurcations, that require more than just a simple predilatation stent implantation. The concept of procedural risk though while it overlaps with complexity, to some extent actually has other inputs. For instance, the ventricular function of the patient whether or not the other circulation is also compromised, so it's a larger ischemic territory, and similarly some things that were previously complex with an evolution of techniques actually don't offer or confer that much greater risk on patients.

 
 
I would say when I did my fellowship training, left main was something that my heart rate got up for and we were worried about the patient in that respect. Now when we do left mains, it's actually something where we view it as one of the more simple things that we do relative to for instance the retrograde approach to a CTO revascularization. There's been an evolution and there's an overlap of what's complex and what's high risk.

 
Carolyn:
Very nicely put. Could you tell us a little bit about how your paper is structured? I really like for example the way your tables are laid out and so on, but maybe just give an overview?

 
Ajay:
Absolutely. I think we start off with just setting the scope of the problem. Basically, looking at coronary heart disease and the fact that there are subsets of coronary diseases for which has prognosticked the importance to revascularize. For instance, the publication of this ten-year result for the first trial [inaudible 00:12:45] revascularization as a whole. We talk a little bit about the assessment of procedural risk and then we sort of move on in the end to the various areas that interventionalists need to become better trained in order to deal with these types of patients. I have to give credit where credit is due. The tables that you like so much were actually the suggestion of the editors.

 
 
Because of the new theory, Manus had a lot to do with this. I think it's very important for people to understand, at least for this paper the role, the back-and-forth conversation between not only us, but also the editors and the reviewers play in bringing this manuscript to its final form. I really give them credit for it. What's in the tables are not only descriptions of the types of multidisciplinary teams that are needed in order to [affect 00:13:27] that we take of these patients. Also, the techniques that would be useful for interventionalists to know how to use and be [inaudible 00:13:33] to take care of these patients. Finally, a table looking at future directions because it's all good and fine for us to say this is a new area and we're moving into it, but we need to sort of generate the research and the evidence base to really support the treatment that we're trying offer or saying we can offer in the manuscript.

 
Carolyn:
Manus, you have to this describe some of this back-and-forth conversation that went on.

 
Manus:
Ajay, I wish that every author took the comments as well as you did because that's definitely not the case. I must admit that it was a pleasure working with you because again you were so open to all the comments and suggestions even though some were tough ones. I think the interaction and being so open I think made the paper better and we're very, very appreciative for your response to those.

 
Ajay:
I think at the end of the day when you have a new editor team taking over, there are going to be changes and some changes you learn how to grow through and other changes you basically adopt what the previous editors were doing. At least my experience, not to [despair 00:14:29], is the prior circulation editors at all, I actually had a great experience with them as well, but this was novel, and I think it's something that for many authors will find quite nice to experience because there was a lot of back and forth. Some parts were contemptuous, but these were all resolved. I wrote in my response back to the reviewers I really do feel the paper was better as a result.

 
Manus:
I think that's the idea that [inaudible 00:14:51] the language and the whole editorial team is trying to enforce and we're very happy with it and enjoyed.

 
Carolyn:
I couldn't agree more. Actually, Manus I was also going to ask the title is provocative. It says this is an evolution and even in the conclusion of the paper that this could be a new field of coronary interventional procedures. I really love your thoughts. Is this a beginning of a whole new field?

 
Manus:
I personally do believe and many people I think do believe that there's a tremendous evolution that is going on right now, continue to go on in the field compared to the early days of [inaudible 00:15:26] where we did simple angioplasty I think it has come a long way. But I think there is gap between what can be done right now in terms of technical possibilities, in terms of equipment we'll have and improved patients' quality and quantity of life.

 
 
Actually, what is being done because as you heard from Ajay, many of those patients who could benefit do not. Within the environment of trying to stop in a [inaudible 00:15:51] procedure, which is very appropriate, what happened exactly is that those more complex and high risk cases because of the fear of complications or sub-optimal outcomes led to offering less treatment to those complex patients.

 
 
I do believe it's an evolution in the field. I do believe that having access to these techniques, equipment and offering options to the patients and explaining there is benefit ratio can bring the patient's life, make them better and bring the field forward to the next step.

 
Carolyn:
Ajay, do you think you could elaborate a little bit more then on what those next steps you think are and what are the future areas of research?

 
Ajay:
Yeah, I'd certainly be happy to do so. I couldn't agree with Manus more. I know he and I share a lot of beliefs in terms of this. One of the things that's important to recognize is while we can all assess procedural risk, some of these advanced techniques are not commonly shared by all interventionalists here in the United States, particularly if you look at the overall case volumes of many interventionalists in the United States, there are folks who are just not going to have the requisite volume to be able to do complex CTO revascularization with a retrograde approach. For instance, they would bring procedural success rates up around 90%.

 
 
I think that some of this is education. You have to sort of understand what can and cannot be done, what can and cannot be done [faithfully 00:17:08] and what techniques you use or are necessary in order to be able to improve this rate of success. If for instance I can't do the procedure myself, then I need to be familiar with somebody who actually can because if the patient merits revascularization, in other words they could benefit from having a procedure done, they're not a surgical candidate and they could be helped by PCI, then rather than saying, "We should just do medical therapy because I can't do the procedure." The appropriate thing to do is to actually refer the patient to somebody who actually could do the procedure in a safe way and therefore ensure benefit for the patient.

 
 
That's an educational aspect. Some of it relates to training, but I think conceptually we do need to start understanding now that there is a sub-specialization within coronary intervention of interventionalists who are able to offer things that many interventionalists cannot. That's somewhat of a fundamental step many people have to take, but I think it's time to take that step and that was the whole point in writing this paper.

 
Carolyn:
I think that is a very effective first step that now you've brought it to light and we're so proud and privileged to be publishing this paper. Thank you so much Ajay, thank you so much Manus.

 
Ajay:
Thanks so much for having us.

 
Manus:
Thanks Carolyn.

 
Carolyn:
And thank you listeners. You've been listening to Circulation on the Run. Please tune in next week for more highlights and discussions.

 
 

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