Feature Interview

Using Fluorescence and Optics to View Lesions During Cardiac Ablation: Interview with Dr. Vivek Reddy

Interview by Jodie Elrod

Interview by Jodie Elrod

In this feature interview, EP Lab Digest speaks with Vivek Y. Reddy, MD about LuxCath’s emerging technology for real-time tissue contact assessment and lesion monitoring during cardiac ablation. Dr. Reddy is the Director of Cardiac Arrhythmia Services for The Mount Sinai Hospital and the Mount Sinai Health System, and The Leona M. and Harry B. Helmsley Charitable Trust Professor of Medicine in Cardiac Electrophysiology at Icahn School of Medicine at Mount Sinai.

What do you see as key issues or deficiencies today in catheter ablation for cardiac arrhythmias? 

I would consider the major issue to be assessing lesion formation. With contact force, we know if we’re touching tissue, but we don’t know if we’re actually making a lesion. The surrogate that most of us use is the disappearance of the electrogram; however, it’s not particularly sensitive or specific for when the lesion is done. You can have electrograms even despite a fully transmural lesion because of the surrounding tissue, or you may not see the electrogram of deeper tissue that is not yet ablated; unfortunately, there is currently not a great way of assessing this. The problem with lesion formation being the key deficiency is that each of us end up using our own method for determining if a lesion is good enough, and that affects reproducibility of the procedure. This is particularly true between operators, but also can happen within the same operator in different procedures. When it becomes so operator-dependent that we suddenly start getting variations in procedural efficacy and safety, this can be a problem. 

How does the LuxCath technology work? What are the key differentiators of this technology? 

It works by using endogenous fluorescence and optics to directly visualize both contact with tissue as well as lesion formation. The fundamental physiology that is relevant is that most living tissue has some amount of NADH in it. NADH is a coenzyme that is in many tissues ­— particularly in high concentrations in mitochondria. It’s also an endogenous fluorophore, meaning that it’s a compound that when you shine light at a certain wavelength, it emits and fluoresces at a different wavelength. That is the intrinsic property of NADH — different tissues have a sort of fluorescence property — so it’s almost like a binary switch for when you’re touching tissue and shining light at a certain wavelength. The LuxCath catheter works by emitting a laser light directly to the tissue, and if there is NADH in that tissue, there will be a fluorescence peak in a different wavelength that the system then records. The catheter has a laser that shines light and can detect the light that comes back, so if there is NADH in the tissue, it will find it. It is important to note that blood does not have NADH, so there will be no signal; however, if the catheter is touching tissue, you will immediately see a signal. It’s comparable to an on/off switch — the operator is either touching tissue or not. 

Another aspect is that when the cell is damaged with RF ablation, then NADH degrades. Because of that, using the same technology, the NADH content decreases during ablation. We’ve seen this in our animal research. Therefore, one can directly gauge lesion formation by looking at the endogenous fluorescence — or lack thereof — of the tissue. Again, the advantage is that it definitively interrogates the tissue. Currently, measures such as contact force, power, impedance, and the duration of ablation are used to give operators an idea of how deep the lesion is. These are all pretty good indicators, but they are indirect and may not be perfectly able to determine what is going on, depending on different flow conditions and other factors. 

Why is it important to measure the metabolic activity of the tissue during ablation?

It gives you an idea of contact. You know when you have contact, because blood doesn’t have NADH. During the lesion, as you deliver the energy, you start seeing it disappear. Another aspect that is also very exciting is that in addition to NADH, there are other tissue structures that have different fluorescence properties. NADH is useful because there is just so much of it in the cardiac tissue. However, if you look at scar tissue, for example, there are other signals that one can see with fluorescence — looking at a different wavelength, we can actually see collagen. So one could use this strategy looking for not only NADH that is mitochondrial, but also potentially for scar tissue. Suddenly, we may now be looking at fibrosis and other things in a very direct way, as opposed to the very indirect way that we currently do things. 

How does this approach differ from contact force sensing? 

The main difference is that with this light-directed technology, you know when you’ve achieved stable and consistent tissue contact. While contact force has given us a new surrogate marker for lesion formation, it is incomplete. For example, with contact force sensing, the operator may believe there’s stable contact with cardiac tissue, but the catheter may actually be sliding across the tissue, and therefore contact isn’t stable. Contact force also cannot tell you if you have consistent contact through the cardiac cycle. Finally, contact force cannot tell us about lesion progression.

Does this technology have the potential to replace contact force as the standard of care?

Absolutely. But let me be clear — I believe that contact force works very well. We are still at the very early stages of this LuxCath technology, but if it is able to get to where it looks like it is going, I think it could certainly replace it as a sensing modality. 

What has been your experience using the LuxCath technology? 

With my colleague, Petr Neuzil (the Director of Cardiology at Homolka Hospital in Prague, Czech Republic), we did a first-in-human study using the first-generation LuxCath system. We knew that the technology worked in animals from our previous research, but nobody knew whether it worked in humans. Therefore, in a series of 11 patients undergoing different types of procedures (e.g., SVT, AF ablations), we used the catheter in a very systematic fashion to assess whether or not one could see the NADH in human tissue. The answer is yes. We evaluated the stability of the catheter, identified previous ablations, and also delivered a few lesions with this catheter to look at lesion progression. Because this was a first-generation system, there were some limitations, including that it was direction dependent — meaning it was only forward looking, so if the catheter was parallel to the tissue instead of perpendicular, so we couldn’t see anything since the light was being delivered into the blood pool. However, the feasibility of the technology looks very promising, so we’re very excited about it. The company is now creating the second-generation catheter, which is a more dedicated catheter that is going to be orientation-independent and will address many of the aspects needed in an ablation and mapping catheter. We have not used that in patients, but the early data is very interesting. 

How easy is it to use? What benefits do you see the approach bringing to EPs and patients? 

It seems fairly easy, certainly from a contact / no contact standpoint — it’s pretty binary. From the perspective of monitoring lesion formation, it looks good in the animal data and seems much better than what we currently have right now. Again, until we’re able to use the second-generation catheter in patients, I can’t say anything definitive. The hope is that if this technology is able to do what we think it is going to do, then I expect that we will be able to make our lesions more effective, avoid gaps between lesions, and possibly make lesions safer as well. However, I think its effectiveness and ability to avoid gaps are the main potential advantages.  

There are several surrogate endpoints for lesion formation, including power, duration and contact force. Could you see the reduction or elimination of NADH in cardiac tissue potentially becoming a direct measure of lesion formation in the future?

Absolutely — we have no direct measure right now, so almost anything is better! Again, I don’t want to imply that this is a done deal — there are still a lot of questions that need to be answered. For example: how deep can we see with this approach? How do we see the NADH in live cells in-between scar tissue? How well can we visualize scar tissue in vivo, and how useful is that? However, despite these questions, I think the technology is extraordinarily promising. 

Where do you see the technology going?

Regarding the timeframe, the company is currently working on the second-generation catheter and doing both animal and biophysical lesion formation experiments. After that, in the not too distant future, we’ll hopefully be able to use this catheter in patients.

Disclosures: Dr. Reddy reports personal fees and equity interest in LuxCath, LLC.

This article is published with support from LuxCath, LLC.