Thomas Johnson. I'm an interventional cardiologist working at the Bristol Heart Institute in the UK.

What is the importance behind the substudy?

So this is a really exciting substudy of the ILUMIEN-IV landmark trial, which clearly was trying to establish the difference between angio guidance and OCT guidance to PCI. And so fundamentally, the whole premise for this is about giving patients a durable outcome in the long term.

The reality is that actually engagement with imaging is more challenging than probably we've considered previously. It's now taken a 1A recommendation and so really there is full justification for using imaging in our practise. But actually many colleagues still struggle to engage with that technology and get the best possible result. So this substudy is focusing on a new kind of iterative development within the OCT, which is this concept of virtual flow reserve, VFR.

So VFR is there to really establish a physiological- like assessment of the vessel alongside the morphology and the imaging that we're getting from the OCT. Now, we focus just on the post-PCI imaging runs and have then retrospectively made an assessment of VFR. And really the purpose of this was to establish if VFR could predict bad outcomes in the future. What's really exciting is that we've shown then that VFR is very effective in predicting future outcomes, and it works alongside and in addition to previously defined markers such as a low MSA, so an MSA less than 4.5 millimetres squared.

So hopefully, we're now at a point where we have further technology, further kind of iterative improvement of the imaging modality to help us as the interventional community have greater confidence at the end of the procedure that we're giving the patient the best possible result.

Could you tell us more about the optical coherence tomography-based physiology assessment?

Well, so this is really just a first step. So as I say, this is a retrospective analysis of the ILUMIEN-IV study. And so really we focus just on its utility at the end of the procedure to tell us if we've done a good result. But the reality is that probably we should be harnessing this earlier in the procedure. And in fact, it may be that in the pre-procedural phase, we undertake the imaging and we get this information from VFR and that then enables us to make maybe better decisions in terms of the segment of vessel we should be treating, anticipating the sizing and anticipating the outcome that we might achieve.

So the real kind of aspiration here would be that this new VFR technology in addition, coming alongside the imaging, enables us to make better pre-procedural decisions and then move to the point that we very confidently achieve the best optimisation in the post-PCI phase, allowing the patient to leave with the hope they never return with another event. That's the aspiration.

What was the study design and patient population?

Yeah, so it's important to acknowledge that obviously this is a retrospective analysis of a previously published study. Obviously, this is the largest study of OCT against angio-guidance. And the really unique element to that is that both the angio arm of the study and the OCT arm of the study finished with an imaging assessment.

And so we have restricted the analysis just to those patients who had a single lesion treated, just for the purpose of trying to establish this clear connection between the VFR we get at the end of the procedure and whether it truly relates to that one lesion that's been treated. Having said that, it's still a very large analysis of over 1,500 patients.

What were the key findings?

Well, so we demonstrated, so importantly if we consider again the initial premise of ILUMIEN-IV, we were establishing a difference between angiography and OCT. So in the original study, you may remember that we demonstrated a difference in minimal stent area in MSA. And so actually we've shown again that with VFR we see a difference, albeit small, but significantly different VFR between angio and OCT: 0.89:0.9. So a slight increase in the VFR.

I think what's most important though is when we come to look at the univariate and multivariate analysis of how VFR predicts outcome, we see actually that VFR alongside MSA is a clear predictor, both in univariate and most importantly in the multivariate analysis for predicting future outcomes. So we can see clearly that as the VFR falls, we see this exponential rise in poor outcomes in target vessel failure. And so really, again, just identifying maybe this is a new metric that we should be using to optimise our results.

How should these findings impact clinical practice?

Well, clearly I'm quite far down a rabbit hole and this is an area of my interest and expertise. But I think the reality, as I have mentioned before, is this challenge we have in terms of having now clear recommendation for the use of imaging, but actually persisting barriers to the use and adoption. And I think one of the fundamental barriers there is actually an engagement of the community, a confidence in terms of interpretation of the results.

So what VFR, I think, provides is a new and fairly simplistic metric of good or bad. And so the hope would be that in offering this in future iterations of the OCT software, Ultreon 3.0, that may well then provide the user, the interventionist with greater confidence and greater ease of use and interpretation of what we get from these image-guided procedures.

What are the next steps?

So I think in many ways the focus has to be about increasing adoption. And so, a lot of that comes to where the barriers are, which are fundamentally education, a perception of time. And so actually this type of iterative improvement — harnessing artificial intelligence, the ability to detect lumen contours, vessel contours, prediction of tissue characterisation — fundamentally those kind of academic pursuits and research interests work in parallel to basically enhance and reduce the time spent for operators in making these assessments intraprocedurally.

So really, I think that the intention is that we just get more sophisticated at detecting and interpreting the results and potentially doing that in a way that doesn't rely upon physicians having to spend a lot of time gaining additional experience and expertise.