Jim, there's a question. Is coenzyme Q10 a mitotrope? You know, that's a good question. That's one of its putative mechanisms of action. It has stood the test of time. It's been out there for about 30 years. I can best say that it doesn't appear to cause any harm, and that's why it won't die. That's why it won't die as a therapeutic agent. I think it works reasonably well in patients with satin myopathy. My own experience is about half patients feel better, and half of them it does nothing. But whether it's a mitotrope, I don't know. I'm not aware of any. Yeah, there's a second question about, it says, in right ventricular failure, um, refractory to fluids and inotropes, etc. When we consider mechanical support, are we impella versus VA ECMO? So, the mechanical support talk was mine. I think, not to avoid the question, the first answer is, if you have oxygenation failure, you're going to need an ECMO. That's the primary. If you have to oxygenate, you have to have an oxygenator in the circuit, and you need ECMO. If you have decent oxygenation and right ventricular failure, then right ventricular mechanical support is a conceivable option. My own sense is that that very much depends on both the acuity and the local expertise. There aren't that many RV impellas put in. Not every interventional cardiologist puts them in. And so, at three o'clock in the morning, finding somebody to put in an RV impella can be a little bit of a challenge, whereas the ECMO technology is much more widely available, and there's much more skill with that. That said, I think it really depends on the situation. Jim or Lakshmi, you have a take on this? Well, we're not using a lot of RV impellas. We're primarily using ProtecDUOs and extracorporeal RVADS. Yeah, we use RV impellas in the context of RV STEMIs, because our cath lab here at Emory is comfortable with that, after an RV STEMI specifically. Outside of that, we basically never use an RV impella, and in most of our patients who require RV support, who already have RV support in place, we use a ProtecDUO or a similar formulation with new catheters that have come out that are essentially a ProtecDUO. And occasionally, we'll do a surgical RVAD. Excellent. You know, Steve, one of the big questions that often comes up that I think you addressed in your talk was this issue of when to escalate. And people have come up with scoring systems, as you know, and a lot of it is just judgment and local practice, and frankly, what time of day it is. How about some of your thoughts there? Yeah, so I'll start with a disclaimer. There is a SkyStock shock scoring, and I am a co-author on that manuscript. I would say the SkyStock scoring is an A to E progression, where A is not so sick, E is extremis. And really, the meat comes in class C, which is classic cardiogenic shock, and class D, which is classic cardiogenic shock failing to respond to therapy. And that's kind of the sweet spot. But of all the classifications, the distinction between class C and class D is the most challenging. So if you're in class C and shock, and you get one inotrope, is that failing to respond to therapy, or maybe you're doing well, and how long do you wait for this inotrope to kick in? I do think that some form of classification is worthwhile. SkyStock is in its second iteration and is by no means a finished product. But trying to, if you're going to study this, some sort of standardization and some sort of classification is worthwhile. Because if one trial picked very sick patients, and another trial picked not so sick patients, then it's really hard to interpret it. And it's even harder to interpret it if you've got some of this and some of that. So let me try one more, since I have some people who know about mechanical circulatory support. So the DANGER trial, actually, last I heard at the ESC meetings, it was at 280 out of a planned 360 patients. And there was some concern, based on the characteristics of people entered into the trial, that the mortality isn't going to be all that high. That it may not get up to 60%, it may be 35%. And if it's 35%, it may not show a difference between the device. Maybe there's no difference whatsoever, but even if the device works a little bit, that may not hit statistical significance. So what do you think's going to... Let me speculate, what do we speculate that the DANGER trial, the big randomized trial of mechanical support is negative? What do you think the community is going to do? Take out your crystal ball. Well, you know, I think that the current climate, and let's put it this way, enthusiasm. For mechanical circulatory support is a bit of a horse out of barn. And people are going to poke holes at it, as you just mentioned, immediately. And to be fair, this is one of the reasons why this space is so difficult to study. I give Judith Hockman so much credit for doing the original shock trial. And the issue of clinical equipoise is so difficult, right? Because even the original balloon pump trial, you and I both know that interventional cardiologists sitting there in the middle of the night with the patient dying are not going to flip a coin. They're going to throw a balloon pump and not randomize their patient. So you get this issue where there is truly clinical equipoise on the investigator situation. And when that is true, often the patients perhaps are not so well. And that's something you alluded to too, Steve, in terms of mortality of these patients. So I think it will, I'll be honest with you, I'm not sure it's going to temper the enthusiasm for more aggressive care because of the unmet need. But I think that's one of the big challenges for the trialists. And I think if the trial is negative, I mean, A-BioMed wants the trial to be positive. But at this point, many centers that do advanced support like ours have moved far beyond the Impella CP and are routinely just using Impella 5.5s in any shock scenario. And so really, some of our data lags what we end up doing clinically and at the bedside. And right now, we provide so much more support than a CP ever could. And we've really moved past some of the support options that are needed. Are studied. Yeah, I think it might temper enthusiasm, particularly in places like Germany and Denmark, where resources are somewhat limited. But I agree. And it's the same three objections, which may or may not be true. The trial was negative, but used the wrong dose. That is, the device was too small. You picked the wrong patients. And you gave it at the wrong time. You didn't do it early enough, et cetera, et cetera. And the results aren't there. You can imagine that that's going to some of them.

coenzyme Q10

mechanical support

right ventricular failure

trials

mechanical circulatory support