Cardiogenic shock treatment in the United States has changed as novel therapies and innovative devices have emerged in the last few decades. But how has treatment progressed overseas?
In this interview, Drs. Nazli Okumus (Allegheny Health Network), and Aman Kansal (Duke University) of the CardioNerds spoke with Drs. Benedikt Schrage (University Medical Center Hamburg – Eppendorf), and Alastair Proudfoot (NHS Barts Health) to discuss the evolution of shock teams in Europe as compared to the U.S.
Dr. Nazli Okumus: Hello everyone, my name is Dr. Nazli Okumus:, I’m a second-year cardiology fellow at Allegheny Health Network in Pittsburgh. I serve as the cardio nurse ambassador for our fellowship.
Dr. Aman Kansal: Hello everyone, my name is Dr. Aman Kansal:. I’m a first-year cardiology fellow at Duke University Hospital in Durham, North Carolina. I serve as a CardioNerds ambassador for our fellowship.
Dr. Nazli Okumus: Today we have the pleasure of discussing the differences in cardiogenic shock in the USA and in Europe with Dr. Alastair Proudfoot and Dr. Benedikt Schrage. Dr. Proudfoot is an intensive care consultant at Barts Heart Centre, St Bartholomew’s Hospital in London. He leads the UK working group on cardiogenic shock and is working in the case mix program and collaborators nationally and internationally to improve registry data in cardiogenic shock.
Dr. Aman Kansal: Dr. Benedikt Schrage is an interventional cardiologist at a University of Heart and Vascular Center in Hamburg, Germany. We are so excited for this collaboration between Cardio Nerds and SCAI SHOCK 2022 with mentorship from Dr. Truesdale.
Dr. Nazli Okumus: I will start with the first question. The mortality from cardiogenic shock remains unacceptably high despite earlier vascularization strategies and advances in MCS devices. The lack of data along with historically high mortality in cardiogenic shock led to the concept of cardiogenic shock team to efficiently recognize triage and manage cardiogenic shock. Can you tell us about evolution of shock team in Europe and its effects on outcomes?
Dr. Alastair Proudfoot: So Nazli, Aman, great to be here, thanks to the invite. So, the honest answer to that would, for me, be that I think we don’t really know, and I think that’s one of the drivers for one of the topics that we’ll speak to later on, which is registry data. For sure, I mean, the data, if you go back to the original notion from Jacob Doll and [inaudible 00:02:08] back in around 2015 about the concept of shock teams. I would sense that in Europe we are much further behind the US, I think probably what is happening is that certainly in specific centers that are very well-defined shock teams and where there are not, my sense would be that there is still a multi-specialty approach to shock.
Dr. Alastair Proudfoot: I think, increasingly though, there is a move towards improved processes and the shock team being part of that, so certainly having some kind of structured algorithms based on some of the data coming out of Inovar, Utah, to really get a sense of which patients and when are going to benefit from, either, invasive human dynamic monitoring or more pertinently mechanical circulation support. But I really think at the moment we don’t know, for example, in the UK there are several large cardiac centers who run shock team, shock programs, but I think it’s still a relatively novel kind of concept. And certainly, from my time in Berlin at the [inaudible 00:03:13] German Heart Center, again they have multi-specialty input but not in the structured fashion that you would know in many ways in the US. It’d be interesting to hear from Benedikt what his take is in his own center and throughout Germany and Europe.
Dr. Benedikt Schrage: So just from my side, thank you so much for being here. I totally completely agree with you, Alastair. I think in Germany, and this is true for most of Europe, I think when talking to colleagues, we do have input from certain involve specialties such as anesthesiology, cardiology, surgeons and intensive care doctors, but it is not as structured as it should be. So, although we treat those patients together, we could do a much better job in organizing and structuring the approach.
Dr. Benedikt Schrage: And I think one thing where we can learn from or one group where you can learn from [inaudible 00:04:06] for cardiac arrest patients, where most of these disciplines are naturally involved. But we are at the moment are not doing a good enough job to transfer these protocols over to cardiogenic shock care and there the responsibility for the patients then shifts a bit depending on who’s there and who’s taking charge. And this, I think, is inferior to having a structured protocol where very fixed algorithms are in line to decide on the best care and involve all the minds which are needed to be involved to get the best outcome for the patient.
Dr. Aman Kansal: Thank you both. Our next question is studies to date have failed to show mortality benefit with balloon pump in AMI cardiogenic shock. As a result, it’s used in Europe has been minimal to none while it accounts for up to 70% of mechanical circulatory support in the USA. Dr. Schrage, you recently published a study in circulation which showed lower mortality with LV unloading using an Impella in cardiogenic shock treated with VA-ECMO. What are your thoughts about balloon pump as an alternative unloading strategy to Impella? Do you think this will increase its use in Europe?
Dr. Benedikt Schrage: That’s an interesting question. Indeed, in Europe and especially in Germany, we do see a significant decrease in IABP use which completely aligns with the publication of the IABP two trial. And instead, we do see an increase in more active circulatory support device such as Impella and ECMO. And to start with this, I think one reason for this is that physicians do believe that the cardiac output support provided by the IABP is not enough in the setting of cardiogenic shock to support the patients. Whereas the more active devices, Impella and ECMO, provide more cardiac output support and thereby more support which is needed for the given patient.
Dr. Benedikt Schrage: And in the light of this, I mean we did publish that the use of [inaudible 00:06:06] LV unloading is associated with a lower mortality in ECMO patients with shock and these were all patients tweeted with Impella. And I think to a certain degree from a pathophysiological point of view, you can transfer this to use of in an IABP, which should also lower the after-load increase provided by the ECMO a bit. However, as it’s a passive device which is only active 50% of the time, I’m not so sure whether doctors in Europe, and especially Germany, on the background of the overall decreasing use of IABP will then turn to the IABP instead of Impella. And another reason is that the potential benefit of Impella use in ECMO patients is not only the initial support phase but also the weaning from the ECMO where you can use the utility of the Impella to provide an active and higher cardiac output support to then wean the patient from the ECMO and then wean the Impella.
Dr. Benedikt Schrage: And I can see, and that’s what I’m hearing from discussion with colleagues, that they’re a bit hesitant to use the IABO in the setting as the cardiac output support is lower. However, on the other side, you have a smaller vascular access with the IABP, we do see a lot of vascular complications with the Impella. So, this might be something which need to be weighted out. But I think most important to notice is that all this data is very preliminary and early as this is from retrospective registry, which are so important to inform us about process, how we do treat and how we could treat shock patients. But we do need randomized data to make this more sure, more firm and we’re currently working on the unload ECMO trial which will hopefully answer the question.
Dr. Nazli Okumus: These are great points Dr. Schrage, thank you. [inaudible 00:07:53] shock trial showed higher 30-day mortality and higher rates of renal replacement therapies in acute MI cardiogenic shock patients who underwent complete revascularization. On the other hand, there is evolving data showing benefits with complete revascularization in non-shock patients with multi vessel disease. Furthermore, recent data suggests that it’s safe to perform complete revascularization with Impella support in acute MI cardiogenic shock. Using the UK and Germany as examples, can you talk first about general differences in cariogenic shock management across Europe and then specifically differences in revascularization for acute MI cardiogenic shock?
Dr. Alastair Proudfoot: Yeah, so I mean I’ll speak to the UK first. So, the basis data, which is our very high-quality national audit data, suggest that subsequent to a culprit shock, there has been a move to culprit only PCI in the setting of cariogenic shock. I think that the challenge to that and one of the challenges we face organizationally is that when treating the culprit vessel doesn’t improve the shock and then do you go on and try and open up other vessels at that time or do you just stick to a culprit only approach?
Dr. Alastair Proudfoot: And I think to your question, the other, I guess, challenge, and I think it’s a really interesting area ripe for exploration, is in an era where increasingly people are using upfront mechanical [inaudible 00:09:30] to support and shock patients, it’s difficult to really get a handle on the risk benefit ratio in that cohort. Where you, arguably, have a bit more time and hemodynamic stability to do multi vessel revascularization, and I think, again, that’s one of the needs for Paneuropean data to really understand what practices are, what the outcomes are and what they associated complications. I think certainly where I work, as I say, we would go culprit only, let the dust settle, get the patient to the intensive care and then do a stage revascularization of any other vessels. And it’d be interesting to see what Benedikt practices and what he gets a sense of in Germany and the rest of Europe.
Dr. Benedikt Schrage: It’s a very interesting and tempting thought, I think we do it very similar as you do. So before [inaudible 00:10:25] shock, we were more in the do more revasc as early as possible side and after the [inaudible 00:10:32] shock trial because we went rolling center and we then tend to stick to what the outcome show, we really try to only do the culprit vessel and then within the first day, we do the complete revasc or in a second stage, depending on the clinical course.
Dr. Benedikt Schrage: But you said something which is really tempting, it is tempting to use the MCS support as an excuse or possibility to do more in the first setting and I think this is really something where we need to collect more data because I mean this could be true. It could be that the Impella or an ECMO or even an IABP gives us more time to do more revasc, which could then be more beneficial to the patient, but it could also lead to more [inaudible 00:11:16] injury, it could also lead to more vascular complications and to more use of MCS in patients where it’s maybe not the right device. And I think this is something where we first need very good registry data to assess where we are at the moment because I’m not really sure what’s the Paneuropean, even US practices on that, how people do that. And then to test the preferred strategies or the most reasonable strategies to see if MCS gives us an extra margin for more revasc.
Dr. Aman Kansal: Thank you both. Dr. Schrage, you recently published a study in the European Journal of Heart Failure which eloquently demonstrated the lack of representation of the majority of cardiogenic shock patients due to restrictive inclusion criteria in the RCTs. What do you think should be the next steps to expand our knowledge and understanding of this population?
Dr. Benedikt Schrage: Yeah, that was an interesting study. So, we kind of just collected the major RCTs on mechanical [inaudible 00:12:15], support in cardiogenic shock and applied their inclusion criteria to a large cohort and saw that most patients are not included in these trials. And I think the IABP shock trial is a very good example for this because, as I said earlier, after publication of the trial, use of the device plummeted by far in Germany, but if you look closely and I mean you do not even need to look closely, it’s just acute [inaudible 00:12:41] shock. Approximately 50% of shock patients do not have an AMI so maybe there’s a point to [inaudible 00:12:47] high use of your IABP in the US.
Dr. Benedikt Schrage: So actually there are two messages, we do need more trials on cardiogenic shock, I think that’s clear, there’s so many open questions, but we then need to actively pursue trials in population which have not yet been covered such as nonischemic cardiogenic shock, those with SCAI B, so a relatively low lactate, but signs and symptoms of cardiogenic shock. We need to try to paint a bigger picture of these patients. Alastair, what’s your point on this? Should we rather focus on less trials to cover more patients or on a lot of trials covering a narrow range of patients and then adding up to a whole picture?
Dr. Alastair Proudfoot: I think it’s a really interesting point and obviously the historical focus has been on AMI cariogenic shock, but the observational data, as you rightly highlight, point to the fact that nonischemic shock is more prevalent in our cardiac intensive care units. And so, the bottom line is that studies remain difficult in the cardiogenic shock population for reasons that we’ll probably discuss in a few minutes, but I think having targeted populations, to me, so what I would do is probably use the registries to collect all comers and then within those registries, look at subpopulations to identify signals. And then probably use those signals to design and power a randomized control trials because I think that the community is moving to this notion, if they haven’t already, that the one size fits all approach is just not going to work.
Dr. Alastair Proudfoot: And it may be, and I think to your point, Benedikt, that there are some data pointing to better efficacy and indeed augmentation of cardiac output in heart failure patients compared to the ischemic patients. And so it may be that one device has a better efficacy and utility and therefore clinical outcomes in a certain population than it does in others. And so, I think we need to use registry data to refine our thinking and hypotheses and then really focus in on patients of interest within that would be my sense however challenging.
Dr. Nazli Okumus: Thank you both. Despite the widespread use of MCS devices, we are still lacking RCTs that show mortality benefits with these devices. There is a tremendous need for more efficient cardiogenic shock research to monitor temporal trends in outcomes and improvements in daily practice. What are your thoughts about building a Paneuro shock registry to close this gap?
Dr. Alastair Proudfoot: Yeah, so again, I think this is a real unmet need in Europe. I mean the US has led the way, so initially, obviously, the National Cariogenic Shock Initiative and then Triple CTN, the Cariogenic Shock Working Group, [inaudible 00:15:57] Shock. And I think that the data that’s specifically come out of three CTN and the Cariogenic Shock Working Group has really started to not just inform our practice, but in the prior discussion is patients of interest where there may be differences in outcome with different approaches. And I think the thing that we really need to get a handle on is the heterogeneity of management and that’s where I think registries give real clues as to what the differences are and how those differences impact upon outcome. And for those of you who haven’t yet listened to it, I think the podcast that was done with [inaudible 00:16:37] with Mario Jessup and David Morrow gives you a sense of the drive for the AHA, not just in understanding heterogeneity, but ultimately using very robust data across a very diverse group of patients to start building guidelines best practices in these patients.
Dr. Alastair Proudfoot: And I think within Europe, I would be reasonably confident that there is huge heterogeneity and that’s been one of the drivers behind a group that I’m very privileged to be part of that includes, Benedikt, collaborators in France, others in the UK, Spain and Italy, to start the beginnings of a registry that we would really like to focus on lean core data, have very little missing [inaudible 00:17:25], but to start to be and to understand practices across the different countries, how that impacts upon outcome. And then really diversify that across Europe to get a handle, as I say, initially on the heterogeneity of practice, which I’m sure exists and I’m sure probably impacts on outcome.
Dr. Benedikt Schrage: I think you mentioned something very interesting, the heterogeneity, isn’t it? I think this is such a crucial part because it’s not only to the, for example, use of different devices, but how we differently use devices. I mean if you have a patient on IABP in one center, his IABP based treatment in another center might be completely different and might use different protocols, might use different techniques to achieve the access. And all this has an impact on the outcome and the perceived benefit risk ratio or the actual benefits risk retro ratio of the device. And this is true for all the devices and there are so many more techniques which interfere, use of renal replacement therapy and so on. So, I think we do need to cover all these areas to get more information and data to then ultimately create protocols and algorithms which really use these devices at the best of their capabilities.
Dr. Aman Kansal: Thank you both. We’ve been having a really great fruitful conversation about RCTs and as we discussed the need for these randomized controlled trials, one specific area with major differences between Europe and the US is a consent process for randomized control trial enrollment. Can you tell us more about the challenges randomized control trials have faced and how we can improve the process moving forward?
Dr. Benedikt Schrage: I mean, this is a really tricky part. So, I mean basically how we do RCTs on shock in Europe, or in Germany, is that, I mean, in almost all shock cases, you cannot get consent upfront so basically need to get it afterwards from the patient, often relatives. And what is been done in here is the so called [inaudible 00:19:30] where you have physicians which are not associated with the study in which you want to enroll the patients, they check the patient for his supposed agreement to or against the consent. And if they do not find any obvious evidence or by building contact to the relatives at the time of their shock. If they didn’t have any reasonable evidence that a patient would be against the trial that he could be enrolled and then afterwards, after he recovers or after a legal representative is named, you then get the final consent.
Dr. Benedikt Schrage: But obviously also this is not a perfect situation because this requires you to have independent physicians who are not connected to the study onsite to interact with the relatives or check the patients’ files. And this takes time and the whole processes is relatively complicated, but so important. I think this is a major hindrance to the enrollment in shock trials, even though we do have a solution here which works, and which led to completion of several randomized controlled trials such as IVP Shock two, Hybrid Shock and soon ECLS shock. But still, this is a problem because if we then say we restrict the population of patients we can enroll because we only enroll those who come during the daytime where enough doctors are present or we can get the best potential information, we can then also limit the generalizability of trial, which will then impact the outcome. So, this is a crucial point to improve this process.
Dr. Alastair Proudfoot: Yeah, I mean from my perspective, I think it’s one of the areas where we’re certainly more fortunate and clearly [inaudible 00:21:20] work in Germany has led the way and we’re ahead, by virtue, in Europe and that relates to the differences around consenting individuals who don’t have capacity. I mean through the cardiogenic shock working group and Neil Dicker and Graham Nickel are doing tremendous work on this, and that, to my understanding, has been one of, if not the biggest barrier to randomized control trials in the US. So, in the UK, we have a similar model of what we call deferred consent whereby we can use a nominated consultee and that can either be an independent physician or a family member, if they’re available to understand what the patient’s wishes would be. Because I think there is an acceptance that the vast majority of patients of interest in cariogenic shock studies are not going to be able to consent because they don’t have capacity.
Dr. Alastair Proudfoot: And I think it is very reassuring that there are moves in the US to try and resolve this, and clearly it’s been one of the big advantages in Europe that we’ve had, and Germany has had and through [inaudible 00:22:30] to really drive the data in this space. But it remains a challenge and I think we increasingly need to work with patients, patients’ groups emphasis to really understand that this balance between respecting patient’s wishes, but at the same time generating the data, particularly in a field where we still don’t know that some of the things that we are doing are not exposing patients to harm as opposed to the benefit that we think we may be offering them.
Dr. Aman Kansal: Thank you both. This wraps up our questions for today. Dr. Proudfoot, Dr. Schrage, thank you so much for joining us. It’s really been an incredible discussion, very enlightening and thank you everyone for joining us as well.
Dr. Benedikt Schrage: Thank you for having us.
Dr. Alastair Proudfoot: Thanks for having me. a real pleasure. Thanks guys.
Dr. Nazli Okumus: This was phenomenal. Thank you.