The Cardiogenic Shock Working Group (CSWG) is a multicenter registry developed to collate clinical data on shock patients from various institutions with the goal of centralizing the data for analysis to yield better outcomes.
In this video interview, Drs. Carrie Mahurin (University of Vermont), and Yoav Karpenshif (University of Pennsylvania) spoke with Drs. Navin Kapur (Tufts Medical Center), and Shashank Sinha (Inova Health) to discuss the registry, and its importance in providing important research on cardiogenic shock.
Dr. Carrie Mahurin: So, my name is Dr. Carrie Mahurin. I am a second-year cardiology fellow at the University of Vermont. I’m a FIT trialist working with the CardioNerds on the PARAGLIDE-HF trial with mentorship from our institutional PI, Dr. Van Buren. I’m still figuring out what I want to do when I grow up, but likely will be pursuing general cardiology with a heart failure focus in my home state of Montana.
Dr. Yoav Karpenshif: Hi, everyone. My name is Yoav Karpenshif. I’m a fourth-year fellow at the University of Pennsylvania doing a critical care year. I’m Penn’s former ambassador for CardioNerds, and I co-chair the CardioNerds Critical Care series. I’m excited to be one of the fellows representing CardioNerds at SCAI Shock this year in Minneapolis.
Dr. Yoav Karpenshif: We are so excited to introduce our experts today. Let me introduce Dr. Navin Kapur. Dr. Kapur’s an international leader in heart failure, mechanical support, and practices as an interventional cardiologist. Dr. Kapur received his medical degree from Georgetown University School of Medicine before completing his residency at Beth Israel Deaconess Medical Center. He completed his general cardiology fellowship as well as both heart failure and interventional fellowships at Johns Hopkins Hospital. After that, he moved to Tufts Medical Center, where he has built a leading clinical and research program in interventional cardiology and advanced heart failure.
Dr. Yoav Karpenshif: He is an associate professor of medicine and the executive director of the Cardiovascular Center for Research and Innovation. His clinical expertise focuses on invasive hemodynamics, mechanical circulatory support, complex coronary intervention, cardiogenic shock, and interventional therapies for patients with advanced heart failure. Dr. Kapur directs the Interventional Research Laboratories and the Cardiac Biology Research Center within the Molecular Cardiology Research Institute at Tufts Medical Center. His research spans basic translational and clinical investigation into the world of heart failure, mechanical support, and the biology of the failing heart. Dr. Kapur is the executive director of the Cardiogenic Shock Working Group, which we’ll be talking about today.
Dr. Navin Kapur: Great. Thanks for having me, and hopefully we have time for the rest of the recording. That was a great introduction. Thanks.
Dr. Carrie Mahurin: And I am equally excited to introduce Dr. Shashank Sinha, who is currently the director of Cardiac Intensive Care Unit at the Cardiovascular Critical Care Research Program at Inova Fairfax Hospital. He is a cardiologist within the Advanced Heart Failure Mechanical Circulatory Support and Cardiac Transplantation Program. He received his undergraduate degree cum laude in applied mathematics from Harvard College and his medical degree with honors from the University of Chicago.
Dr. Carrie Mahurin: He completed his internship and residency in internal medicine at the University of Pennsylvania, and he then went on to the University of Michigan, where he completed his clinical fellowship training in cardiovascular disease and advanced heart failure and transplant cardiology. He also completed a two-year research fellowship and Master’s program in health and healthcare research at the University of Michigan Institute for Healthcare Policy Innovation.
Dr. Carrie Mahurin: The primary focus of his research is to understand and improve the quality of care of patients experiencing critical cardiac illness, including cardiac arrest, cardiogenic shock, and acute decompensated heart failure. He is the principal site investigator for the multicenter Cardiogenic Shock Working Group, which examines acute mechanical circulatory support devices and cardiogenic shock.
Dr. Shashank Sinha: Thanks very much for having me. Truly an honor and privilege to be here with all of you and, of course, with my mentor and role model here.
Dr. Yoav Karpenshif: We are so excited to talk about the Cardiogenic Shock Working Group today. So, Dr. Kapur, the Cardiogenic Shock Working Group Registry is a massive undertaking, recruiting thousands of patients across 23 sites nationally. Its mission statement says that its goal is to improve outcomes for patients with cardiogenic shock by promoting rigorous scientific investigation, inclusive of retrospective and prospective clinical studies to generate real world evidence for this deadly problem. Can you tell us about the motivation behind starting this registry and what it took up to set up something so far reaching?
Dr. Navin Kapur: Yeah. I think the motivation is the same thing that motivates all of us here on this call, which is to take care of the sickest patients. In cardiovascular medicine, cardiogenic shock remains really one of the most tragic unsolved mysteries of our time. We still are seeing about 40% to 60% mortality rates in patients, especially among AMI patients, where you would think you’d have a lot of advanced therapies for immediate revascularization. And the realm of heart failure shock is really untapped. It’s an area where we see a lot of interventions, therapies, but we don’t have any data.
Dr. Navin Kapur: And I think that’s really what I found most frustrating as a trainee at Hopkins, learning from the best minds about how to be a great clinician, how to think about interventions that would help patients, but not having any data for a lot of the things we were doing in our critical care environment. And I think when I started joining as a faculty member at Tufts as an interventional cardiologist and a heart failure specialist, that started to become even more granular because the sickest patients would come to the cath lab, and there would be a lot of confusion about what to do next.
Dr. Navin Kapur: And over the past 15 years, we’ve seen a significant acceleration of mechanical support options for these patients that’s now left the operating room and entered the interventional cath lab. And so, as a result, they’re more readily available to a broader group of operators. And as a result, we’re starting to see that these devices are being implemented, but again, with limited data.
Dr. Navin Kapur: So, what drove my personal mission to start the Shock Working Group was to start to generate data and to do this in partnership with friends across the United States who shared the same passion to solve this problem. So, it started off with a small group of investigators pooling data. Each of us had our own registry, and we decided to try to combine the registries, which turned out to be a massive undertaking when you try to do it on Excel, and you try to do it in the pre-Zoom era. So those emails were quite challenging.
Dr. Navin Kapur: But I’d say probably about four years ago, five years ago, I decided that I’m either all in or I’m going to go onto something else. And so by going all in, that meant creating an operational structure that allowed for industry funding to come in and basically enable the development of a REDCap database that could be broadly implemented across institutions in the US, expanding to a steering committee that’s led by leaders and emerging leaders like Shashank on this call, and putting together minds again that are passionate about the field, and now accelerating our database from a few hundred patients across a couple institutions to now thousands of patients being accrued every year.
Dr. Navin Kapur: So, we’re over about 5100 patients right now. We accrue at a rate of 2000 patients per year. There are 23 centers currently enrolling in the version three or year three data set that just closed out. We’ll expand to 30 sites and then over the next three to five years expand to 40 sites. And the Shock Working Group will now start to transform itself from a registry that collects data retrospectively and also tracks prospective outcomes to now becoming a platform for clinical trials. And those clinical trials will be informed by the database and will be implemented within the Academic Research Consortium of the 30 to 40 hospitals. So that’s sort of the genesis and the direction for the Shock Working Group as it stands in 2022.
Dr. Carrie Mahurin: Awesome. Dr. Sinha, to expand, I know we sort of just touched on this, but on the motivation behind the Cardiogenic Shock Working Group, do you have any specific goals or targets for this as far as research goes, specific areas that you hope to see this go? And how do you anticipate that changing the management of cardiogenic shock? And furthermore, just one last part is, there are clear advantages, obviously, as we just discussed about this working group, but are there any disadvantages having this registry?
Dr. Shashank Sinha: Well, great questions, and I’ll tackle them one at a time. I think to embellish upon what Dr. Kapur just noted here, we’re very excited about this next decade in cardiogenic shock. It’s been unfortunate that over the last two decades, mortality really has persisted at 40% to 50%. And we’re finally being able to make a little bit of a dent with the advent of shock teams and some sophisticated algorithms and nuances with respect to the etiology of shock, heart failure shock now being the most common and prevalent, the phenotypes of shock, which we’ll discuss a little bit later on today’s call, and then some sub-phenotypes, which are coming through some machine learning approaches through the Shock Working Group itself.
Dr. Shashank Sinha: I’m particularly excited about our first clinical trial. It’s called PACCS or the PA Catheter in Cardiogenic Shock trial, led by Dr. Kapur, Dan Burkhoff, and Manreet Kanwar, who are the National PIs. And I encourage listeners to listen to the accompanying recording with those interviewees and national experts about that trial.
Dr. Shashank Sinha: But briefly, it’s remarkable that in 2022, the ACC, AHA, and HFSA guidelines actually give it a class 2b recommendation for placement of a PA catheter in the management of cardiogenic shock. And what we’ve discovered is that there is equipoise primarily because the distribution seems to be bimodal between those who clearly believe that we need a PA catheter to help influence management and appropriate device selection, an institution like Dr. Kapur’s and mine, where that utilization rate is greater than 90% for cardiogenic shock patients, and data from the NIS and others that suggest that it’s actually more nominal at 30% in managing these patients.
Dr. Shashank Sinha: And so looking at this data, looking at the fact that the mortality curve has not really shifted significantly, we feel like this is an important trial, especially in the backdrop of recognizing that 90% of the trials in cardiogenic shock are done outside the US, and really 90% of them are done probably in AMI shock just as sort of a back of the envelope estimation. And so, Dr. Kapur’s team at Tufts has already randomized the first couple patients in the PA Catheter in Cardiogenic Shock study, and at least at the time of this recording, we’re hoping to become one of the next sites to be activated so I think the future is exceptionally bright.
Dr. Yoav Karpenshif: Well, we are very excited to see the results of that trial because that will definitely affect all of our day-to-day practices.
Dr. Yoav Karpenshif: Dr. Kapur, a body of evidence has already been published based on this registry. One theme that’s come up across multiple papers is the idea of phenotyping cardiogenic shock. Why is this such an important goal for the group, and how do you imagine these findings will affect patient care and influence future inquiry?
Dr. Navin Kapur: Yeah. I think the phenotyping and profiling of shock is one that I personally find really interesting. When I got into this space about 15 years ago as a junior faculty member, it became pretty clear that we weren’t all talking about the same patient. We had doctors who would come in and say that patients in the early phases of shock, this patient looks like they’re in deep shock, pre-shock, kind of shock, shocky. And there were all sorts of words that had virtually no meaning that we were using on a day-to-day basis. So, it became pretty clear that when I first started managing these patients on my own, we started to look at patients as hemodynamic shock versus hemometabolic shock. And that was sort of a broad characterization just based on what we were trying to do on a day-to-day basis.
Dr. Navin Kapur: But it became also further clear that that was insufficient. And when we started to think about patients in terms of their congestive profile or developing an algorithm for how to manage these patients, we really had to think about how are we targeting our therapies to specific subsets of patients. And then it became even more clear that a lot of physicians and operators and doctors and physicians caring for these patients had biases. They had their own particular bent towards what an AMI shock phenotype might look like. And I’ll never forget at the ACC, I think it was in 2015, walking into a room where the announcement was made that the title of the plenary was Impella for All Doc. And yeah, I was blown away because I had never really thought of a device in that way, that it was really the ultimate and only treatment for this really complex clinical problem that was multifaceted, multifactorial.
Dr. Navin Kapur: And so that made it pretty clear that we really needed to start to pheno profile patients better. And we started to implement and publish the first machine learning paper in cardiogenic shock from the Working Group Registry. We have a lot of excitement around advanced data analytics, and there’s now a cadre of folks who live in that world that are now part of Shock Working Group. But I think what’s also really important is if you look at all the clinical trials that have been done in the space of cardiogenic shock, the ones that have been semi-successful, because it’s really hard to find one that’s been successful, have really focused on a subset of a subset of patients. [inaudible 00:14:26] shock, for example, is really the one that probably has a significant P value, but I always put the term positive trial in quotes because the mortality in both arms was 46% and 55%, so positive with a B value, but still not really moving the dial. And that really focused on a subset of a subset of AMI patients.
Dr. Navin Kapur: If you look at the DOREMI trial, they enrolled SCAI B through E as the inclusion criteria. So, a broad swath of all sorts of pheno profiles with MI and heart failure etiologies in the P value with NS. So, I think what we’re trying to do now with the Shock Working Group data and this mindset of pheno profiling is target specific patient populations where we think interventions can be applied almost in a tailored manner. And a great example of the pragmatic trial that pulled this off was the ARREST trial, which looked at ECMO versus ACLS or resuscitated, well, out-of-hospital cardiac arrest or arrhythmias. And with a strong P value, but an N of 15 per arm, 30 patient study, this group really threaded the needle. They narrowed down the inclusion criteria to a clinically relevant subset of patients.
Dr. Navin Kapur: Now the challenge there is how broadly applicable is it when you start to go into subsets of subsets of subsets? So, I think there’s a balance there in terms of pragmatic trials. The PACCS trial, when you start to learn more about it, I think, really starts to target the decompensated heart failure patient who has an elevated lactate. And that’s a broad number of patients. And it’s a pragmatic intervention of early invasive hemodynamics versus [inaudible 00:16:10] or delayed hemodynamics. So that’s the idea about pheno profiling. That’s why we think it’s important. And also taking the bias out of the analysis, I think, is that scientific rigor we were talking about earlier and making sure we’re applying the best techniques in 2022 to this data set.
Dr. Carrie Mahurin: That’s awesome. I think I heard that a patient was shocky just today, so I think that really hits home that we need to really divide these patients into individual groups. Dr. Sinha, I noticed that the majority of programs involved in this group are so far large, quaternary care facilities who have access to a ton of resources, all of the above of a cardiac ICU, MCS, ECMO, et cetera. And this makes sense from a registry standpoint to create a universal population set in which to go off of. But do you think that this data generated will be applicable to tertiary care centers with not as many resources available? And are there plans to enroll these sites into the Shock Working Group?
Dr. Shashank Sinha: Well, it’s an excellent question. And we just had our steering committee meeting that Dr. Kapur led a few weeks ago, and this specific question actually was raised. And I’m pleased to report that that is a very strong interest of the Cardiogenic Shock Working Group. Indeed, we are interested in providing the foundational evidence base for what systems of care delivery for cardiogenic shock look like by having those systems be part of the Shock Working Group.
Dr. Shashank Sinha: We have enrolled some systems in the Southwest, some systems in the Southeast, some systems in the Northeast, and then I’m in the mid-Atlantic. And we hope to continue to expand that scope, as Dr. Kapur was referring to, enrolling 25, 30, and then potentially even 40 sites in the next three to five years, so that we can truly study networks that are providing shock care, understanding what is the optimal time to transfer a patient. Is a hub-and-spoke model truly the preferred model of care delivery, or are there tier-based networks that may behoove us? These are important questions. They’re largely unanswered, and I think that we are very fortunate to be in a position to study them as rigorously as we have, using our registry data thus far.
Dr. Yoav Karpenshif: Thank you. Dr. Kapur, I know going through all of our minds right now is the amount of data that is being generated from this undertaking. You mentioned an expanding network. You and Dr. Sinha both mentioned an expanding network, 2000 patients a year, all with multiple data points. So, I imagine that this data set will be the basis of inquiry for many projects for the foreseeable future. As a fellow, and if fellows or faculty have questions that they think could be answered by this data set, how can they get involved? There seems to be a lot here.
Dr. Navin Kapur: Yeah. Absolutely. And so, we’re really excited. Over the past few years, we’ve started to see more engagement, not only from the PIs at specific sites who are managing the patients and who are overseeing the registry in their programs, but also from fellows at those sites, and also fellows who are not at Cardiogenic Shock Working Group sites. And I think that’s an important component of the Shock Working Group. One of the major areas of focus for us is the pursuit of the truth. And that’s what science is all about. And having fellows involved, I think, is critically important because they really do represent an important group of physicians who are now emerging, who will be going out to clinical practice, but for decades will be leading the torch. And to get them involved early, to get them around this mentorship team of multiple really senior PIs who are plenary physicians and scientists in the field, I think is really a great opportunity.
Dr. Navin Kapur: And what we’ve started to do now is see the emergence of fellow leaders who are beginning to start to take the lead on projects. It’s one of the most important things I found. If you read my pub med list, I try to stay as the senior author as much as possible and have my fellows and mentees always as first author. It’s one of the things I learned at Hopkins is this really critical aspect about mentorship. And because we have a statistical team that works with us because we have access to resources that fellows may not have at their own institutions; a lot of that work is now being done by our teams. So, for example, if a fellow wants to get involved, they’re welcome to email any of the steering committee members to bring their ideas to the table. Our Wednesday multi-PI call is open to fellows who are interested in participating.
Dr. Navin Kapur: And what we do now, with specific projects, is we have a PI take the lead. Maya Guglin is running an analysis right now on BMI in cardiogenic shock and trying to understand the obesity paradox. She now runs a breakout group, which meets separately from the Wednesday call. And that breakout group will include fellows as well as faculty members of the Shock Working Group to get all the work done. And it’s an immense amount of work but cranking out about 5 to 10 papers a year and also about 15 to 20 abstracts a year can’t happen without the work of all of our members. And so, fellows are very welcome. I think the best way to access Shock Working Group is to reach out to a steering committee member and come with your ideas and come prepared to jump in and get the work done. So, we’d love to have you on board at any time.
Dr. Carrie Mahurin: That’s awesome. Well, I think all of us at the CardioNerds group, in general, want to thank both of you for joining us today in the SCAI Shock 2022 Collaboration with the assistance of our mentor, Dr. Alex Truesdell. I think speaking from all of us, we are super excited about this working group and this registry. It’s long overdue, but understandably a huge undertaking. So, I’m excited to see how this turns out.