The recent DanGer Shock trial sought to assess if the use of left ventricular mechanical circulatory support using Impella CP transvalvular microaxial flow pump enhances survival in patients with cardiogenic shock.
In this interview, Drs. Nazli Okumus and Saahil Jumkhawala of the CardioNerds spoke with Dr. Jacob Eifer Moller, one of the study’s lead investigators, to find out more about this analysis and its implications.
Dr. Nazli Okumus: Hello everyone. My name is Nazli Okumus. I’m a second-year general cardiology fellow at Allegheny Health Network in Pittsburgh, and a CardioNerds FIT Ambassador.
Dr. Saahil Jumkhawala: Good morning everyone. My name is Saahil Jumkhawala, and I am a third-year internal medicine resident at the Rutgers New Jersey Medical School Program. And I am a CardioNerds Academy fellow. Happy to be with you all today.
Dr. Nazli Okumus: This interview is part of a CardioNerds SCAI SHOCK 2022 collaboration with mentorship from Dr. Alex Truesdell. Today, we have the pleasure of discussing DanGer Shock Trial with Jacob Moller who is a professor at the University of Southern Denmark in acute heart failure. Dr. Moller is also a senior consultant at the Cardiac Intensive Care Unit at Copenhagen University Hospital Rigshospitalet. I hope I’m pronouncing it right. Dr. Moller, please correct me if I’m wrong. He participated in several national and international research groups and is the principal investigator of the DanGer Shock Trial, which is designed to compare left ventricular mechanical circulatory support with Impella CP to conventional guideline driven treatment in acute MI cardiogenic shock.
Dr. Nazli Okumus: Dr. Moller, thank you so much for being here with us today to speak about the very important Danish Cariogenic Shock Trial or DanGer Shock. What do you hope that this study will help illustrate regarding choice of treatments for cariogenic shock in the acute intensive care setting?
Dr. Jacob Eifer Moller: Well, thank you for having me and giving me this opportunity. You say Rigshospitalet very nicely. So, for DanGer Shock, I think that is a piece in the puzzle on how to treat cardiogenic shock. At the moment, it’s mostly empirical work we do, we know revascularization works. We don’t know much else can improve outcome. Mechanical circulatory support makes extremely good sense in these cases where the heart can’t do the job, you put the motor in that does the job and that must be beneficial. But these motors come at a cost both for the heart and for the body. So, we need to test whether this works. And I think DanGer Shock is a first step in that direction that will test whether a routine use of this device is beneficial for these patients. But it’s only one step. It won’t be the complete answer.
Dr. Saahil Jumkhawala: Absolutely. Well, thank you, Dr. Moller. We know that there are also many factors that inform the choice of specific circulatory support employed in each case. Given that the placebo comparator is that of conventional circulatory support, how do you believe that operator or cultural variability among the different sites may impact the results, especially with increasing background use of the Impella family of devices as standard therapy in some practices?
Dr. Jacob Eifer Moller: I think that’s the tough and very, very good question. Firstly, I think the thought of introducing drug for heart failure without testing it, nobody would use the drug. So, we have to test these devices in randomized trials. For the comparator, that’s difficult because some places think you do harm if you place an Impella. Some places think you do harm if you put an ECMO into a patient. And that is why these studies are so important.
Dr. Jacob Eifer Moller: So, for DanGer Shock, the comparator will be pharmacological therapy and if that’s inadequate, ECMO. That’s what I’ve done in the sites that are participating in the study, and I think that’s a fair comparator. It’s a European study and they are German sites, and they obviously believe in [inaudible] balloon pump study. So did we when it came out. So, there is very little balloon pumping in DanGer Shock, but there a fair amount of ECMO and I think that is the true comparator for this study. So, if drugs are inadequate, some patients are placed on the ECMO, and I think that reflects common practice.
Dr. Nazli Okumus: So how do you think the increased use of more robust auxiliary Impella devices such as Impella 5.0 or 5.5 effect result and general ability of the study?
Dr. Jacob Eifer Moller: Again, that’s an important question. If I had the luxury of placing 5.0 or 5.5 in the same time as I can place a CP, I would do it every time because it’s a better and more powerful device. But it takes time. You need a graft on the axillary artery in most cases and therefore, you cannot do it within five minutes where you can place an Impella CP. So, until a more rapid access, the device that can deliver five liters, it is the CP because time is mortal in these patients, they all have large STEMIs, so they need to be immediately revascularized and you cannot delay that until you have a surgeon that put a graft in. So, I think not for the forthcoming years there will be devices available. So, the Impella CP is the right comparator here.
Dr. Nazli Okumus: And I see that the primary end for your endpoint here is that from all causes at six months. Would you be able to share some background as to how that was chosen?
Dr. Jacob Eifer Moller: Yeah, that was something that went into some discussion when we designed the study 10 years ago. And I still think there’s only really one outcome you can have in cardiogenic shock trials and that is death from all causes. The death rate is so high that any other endpoint would not make much sense.
Dr. Jacob Eifer Moller: And the other thing about the duration, if you remember the shock trial from Judy Kaufman, the study was neutral on the primary endpoint which was a 30-day mortality, but positive at the secondary endpoint that was 180-day mortality. And I think that’s an important lesson that this is not a condition that is over in 30 days. We have a good few patients in this study that are not discharged at 30 days, so they’re still hospitalized. And using 30-day as a quarter of there, seems not right if the patients are still in hospital.
Dr. Jacob Eifer Moller: So, we want to capture the disease. I know from a publication standpoint, we might miss the chance of having two high impact publication, one after the 30 days and one after one year. But I think the right choice is to look at the disease and look at the outcome then at six months. If we had to do it over again, I would choose the same again.
Dr. Saahil Jumkhawala: Dr. Moller, one of the secondary endpoints listed is cost of treatments. And as we know, health economics are really crucial when we’re discussing such costly, innovative cutting-edge interventions, especially in the critical care setting. So, what impact do you think that answering those questions will have and how do you think that we can draw implications into practice beyond the Danish healthcare system?
Dr. Jacob Eifer Moller: I am really, really puzzled how the cost analysis will be because if we save lives with the Impella, like I really, really hope and believe we will, it will be very expensive lives. So, we may very well end up saying that we save lives but at a very high cost, and that will give some discussion as well. But I think it’s a very important discussion also to have how costly that this strategy will be. So, I think it’s a very important that it’s something we have really focused in on, in the study and it’s one of the key secondary endpoint is the health economy evaluation. But I’m really not sure how we will interpret this, but it will be exciting as well.
Dr. Saahil Jumkhawala: Absolutely. And we look forward to seeing the results. Pivoting slightly, Dr. Moller, you recently published a groundbreaking study in the Journal of American Heart Association last July discussing the different phenotypic variants of cardiogenic shock. In that paper, they were divided into clusters of non-congested or one, cardiorenal or two and cardiometabolic or three shock. How do you think that the choice of Impella versus conventional circulatory support may vary across these phenotypes and do you see these groups being stratified in the future trials?
Dr. Jacob Eifer Moller: We are planning a sub-study based on these phenotypes in DanGer Shock to look into whether there will be an interaction with these phenotypes and the effect of the pump. I think it’s very important to look into phenotypes. Even in DanGer where we have attempted to have a homogeneous population only having STEMIs, excluding out of hospital cardiac arrest, that the population is very heterogeneous. So, we need to dive into does this device work as well in SCAI class C, as in SCAI class D or E, which are also represented in the study. Do these metabolic renal phenotypes, do they benefit the same way? And it can very well be that it is not the case that the cases that are more multi-morbid will have less effect and the more pure SCAI class C, low cardiac output, not a lot of comorbidities will have much better effect.
Dr. Saahil Jumkhawala: So, that will be exciting sub-studies and very crucial sub-studies and we will be challenged on power here in the study. So, it will not end with DanGer Shock. Even if it’s positive, we need more studies to understand this disease more because it’s so many diseases we call the same.
Dr. Saahil Jumkhawala: Absolutely. Well, we really look forward to seeing the results. Thank you so much, Dr. Moller, for taking the time to be here. This is really incredible and thank you for all the work that you’re doing in DanGer Shock as well. Thank you everyone for joining us today and take care.
Dr. Nazli Okumus: Thank you.