Editor’s 2025 Top 10: Can IodixAnol ReducE the Incidence of Adverse Renal or Cardiac Events in Chronic Total Occlusion Interventions (CARE-CTO): A Substudy of the PROGRESS-CTO Registry

Dr Deepak L. Bhatt, editor-in-chief of the Journal of Invasive Cardiology, catches up with Dr Emmanouil Brilakis about his Editor’s 2025 Top 10 article, “Can IodixAnol ReducE the Incidence of Adverse Renal or Cardiac Events in Chronic Total Occlusion Interventions (CARE-CTO): A Substudy of the PROGRESS-CTO Registry.”

Dr Bhatt: Hello, I'm Dr. Deepak Bhatt, the director of the Mount Sinai Fuster Heart Hospital and the Dr Valentin Fuster Professor of Medicine, and also the Editor-in-Chief of the Journal of Invasive Cardiology. I've got the great pleasure of having a good friend with me today, Dr Manos Brilakis, who is internationally known for many things in the field of interventional cardiology, but especially treating CTOs, or chronic total occlusions. He made the Top 10 list for the Journal of Invasive Cardiology last year for the article from his group referring to the PROGRESS-CTO substudy looking at iodixanol and whether it can reduce the incidence of adverse renal or cardiac events in CTO interventions from CARE CTO.

Manos, it's great to have you.

Dr Brilakis: Thanks, Deepak. Again, great pleasure to talk to you, and thanks again for publishing our articles in the Journal of Invasive Cardiology. We love the journal, and it has many practical insights for interventional cardiologists.

Dr Bhatt: Well, thanks for that. Yes, it is meant to be very practical for the practicing interventional or invasive cardiologist. We also do have some electrophysiology and diagnostic catheterization stuff in there, too.

So, let me just start by asking, what was this study designed for? What was it about?

Dr Brilakis: Thank you. The study looked at the different contrast agents that we use for doing CTO interventions. As you know, CTO interventions can be lengthy, there's a large amount of contrast, usually over 200 mL, and the patients who undergo these interventions are usually older, they have more comorbidities, so they're at increased risk of having complications, including acute kidney injury (AKI).

The question here was whether the type of contrast, specifically iso-osmolar vs low-osmolar, can make an impact, both on the risk of AKI, but also on the risk of adverse events.

Dr Bhatt: Yes, really important. The question comes up every day. Of course, this wasn't a randomized study, but what did you find?

Dr Brilakis: It was several thousand patients; the PROGRESS CTO is a very large registry. From those patients, about to 1 in 5, so 18% of those patients, received an iso-osmolar (iodixanol [Visipaque; GE HealthCare]), and the other 80% or so received a low-osmolar agent. What we saw is that the ones who received the iso-osmolar agent were much older, they had more complex lesions, higher Japanese-CTO score, more calcium, and more comorbidities. But when adjusting for all these risks, they had about 30% less risk for AKI and numerically (but not statistically) lower risk for major adverse cardiac renal events.

So, overall, it was a higher risk group where the operator chose to use these iso-osmolar agents. Despite that, their adjusted risk for AKI was lower than that of patients who received a low or smaller injury.

Dr Bhatt: Very interesting finding. How do you reconcile it with randomized data?

Dr Brilakis: There's been many studies on this, some were positive, some were negative. There's some meta-analysis also, some of them showed less incidents, and some of them showed similar incidents. But overall, it does fit with the overall trend that there's some benefit for using iso-osmolar agents. Now, this is just one component, just to make sure we discuss it.

There are also other important things. For example, using hydration before the procedure, which is something we don't collect, but it's critically important, and of course, limiting the volume of contrast that we use for those patients. The less contrast we use, the better it is, but of course, in those complex procedures, sometimes you have to use more, depending on how the procedure goes. But taking that into account, using iso-osmolar agents might provide a benefit and reduce the risk of AKI, especially in sicker patients, those with comorbidities, diabetes, and pre-existing chronic kidney disease.

Dr Bhatt: That's really a useful answer. So, for our audience, then, what's the bottom line? What should they do in practice, factoring these data, you know, the prior randomized data, meta-analyses, cost, etc. What should they do?

Dr Brilakis: I think it depends on every institution, but if people have access to iso-osmolar contrast agents, then I think for complex procedures, such as CTOs using an iso-osmolar agent would make sense, especially in patients who have CKD or diabetes or other risk factors for AKI.

And this is what I personally do in my practice. I think the patients who need CTOs or other complex lesions, especially if they have comorbidities, then we will use an iso-osmolar agent. There is the issue of cost, as you mentioned; but, given that these procedures, are not like the standard diagnostic procedures, these are complex procedures, the cost of the contrast agent itself might be offset by potentially avoiding complications. AKI can be an expensive complication if the patient may have to stay in the hospital longer, so actually, it might be cost-effective in the end.

Dr Bhatt: My practice mirrors yours. If I know I'm going to use a ton of contrast, it's also my go-to agent. The other utilization might be if you're going to do really complex peripheral or cerebrovascular work, that's another potential area where I perceive that there's value.

Any final thoughts or comments to our audience?

Dr Brilakis: Again, these procedures are complex. I think having the iso-osmolar can help, but also the other thing to not forget is to have someone in the cath lab, whether it's a tech or the nurse give us an update, and say, okay, you've given 100 mL of contrasts or 150 of contrast, or 200, so then you know that you don't overdo it, and then at the end of the case, now you've used 500, and now you're in real trouble. So having awareness of how much contrast you are using can go a long way.

Dr Bhatt: I agree, that really is a key thing. Let me just ask you one last thing that popped in my head, since we're talking about contrast utilization, pre-hydration type of contrast. What about the ACIST system? Do you think there's any value in that vs this manual injection?

Dr Brilakis: Great question. We don't have a system in our lab; I use it when I do live cases, but not in our lab. I think it does help, because you have the number, you know exactly how much contrast you've used, so it gives you awareness on how much you've used.

There are some caveats. For example, in CTO, you're going to be careful not to inject very strongly, especially when you're dissecting and doing some more advanced, antegrade reentry techniques, so in those cases, it may be best to have the manifold so you can control exactly how much pressure you put.

Dr Bhatt: Terrific, thanks for that. Well, this has been a great interview, really very informative. Thank you so much for all the knowledge you've shared today, and all your great contributions to the field, and of course, your great papers to the Journal of Invasive Cardiology.

Dr Brilakis: Thank you so much.

The transcript has been lightly edited for clarity.