Staged PCI of Calcified Distal LM/LAD using Orbital Atherectomy

[00:00:00]Good morning and welcome to our monthly webcast. I am Samir Ma your moderator.

[00:00:06]This is session number 205.

[00:00:10]I am delighted to introduce a eminent guest who is joining us in the Kath lab joining Dr. Sharma and Dr. Kenny is Dr. Roberto Bautello. Uh I have known Dr. Bautello now for the last about 20 years. uh to me he represents the person who knows the best about tele medicine applications in medicine and uh he taught me everything about tele medicine. Dr. Bautello is the president of the Jateni Foundation named after Dr. At Jateni whom I had a pleasure of meeting him in 2012. The Jateni Foundation oversees uh uh the Dante Pasani hospital uh uh which is a institution which we know that uh brought the Johnson and Johnson coronary stent to the interventional cardiology world. We'll talk more to Dr. Bello.

[00:01:10]Roberto welcome to you Sam and Anu. Good morning. We have a truly complex calcified lesions and I'm sure Dr. Kiny or you will start by introducing to us your new fellows.

[00:01:23]>> All right. Good morning to all our CCC live uh viewers and uh which has been increasing and the demographics are changing which will show that uh but uh continue the same mission uh select a case and try to make the points on the complex case how can we can we make it simpler uh with that note uh want to of course we welcome Dr. Roberto Bethalo in our cat lab and he has been part of our CCC symposium complex colony symposium many times and of course some Indian meeting and welcome Roberto and we'll take your input in a very complex case and know >> yeah know I'm introducing our two new fellows you know July 1st we start we have France Berkins >> and he's actually from Mount Sana cardiology fellowship originally from Amsterdam completed his PhD there and now stayed here to learn from us and he plans to go back and then we have a Gregory Ofia who is right there he's actually from Ireland. Yeah. Yeah. So we have like a multicultural from multi country everybody come to learn here and both of them are interventional fellows and uh already first uh you know few weeks are done they are ready to do all the complex cases with us for the next few months and rest of the staff is the same as if and naira at the CVT uh and from nurses Mark and Bill and Kishki on the OC on our imaging uh and so so with that note if Okay, we start our case, our CCC live cases, our target audience, the overview and the learning objectives remain the same and we are thankful to Broadmat AV uh doing all our uh propag you know live relays. Uh this is no change in the financial disclosure and then of course we added our guest moderator today Roberto. So now these are our commercial supports by the the font size tells us that how much they support but everybody wants to be the part of our this ever growing CCC live. So this is basically that now things have gone it started with the coronary 2009 2012 peripheral structure 2015 now we added the imaging and microvascular so all types. So every week there is some educational teaching uh from uh on this banner of the CCC live webcast and live uh live webcast and this is actually very interesting put in the one slide overall over the years you can see last two three years around 28 29,000 hits uh per month uh and more important is the demographic is changing so if you take the first last two years of the 2004 to 2025 the United States and India I put it only first four and then last year uh I mean in the basically 25 from January to June of 25 you can see that India has superseded in CCC live and with the percentage of the 28,000 people and now actually we very interestingly the China has climbed up and India is has beaten I would say USA and we know Samir you know it also by going to India everyone is so thankful what we teach on this point with without any you know commercial bias and really try to teach everybody the technique of the intervention. So with that note uh let's go to our today's uh uh presentation of the case number 205 with 81 year old who presented actually was did good this is age of 80 not much little bit here and there slight blood pressure issue but and cholesterol and the and has a and then he was he had a very high coronary CTA I mean calcium score and had a three vessel and left main and they did CTFR positive in all the vessels. risk factors on the left side well controlled and he you know epexib aexiban tovastatin and some anxolytic no other medicine so cat actually will show revealed also three vessel left main which came on the CTA uh ejection fraction was normal look at the calcium everywhere which we expect at age of 81 this was a very calcific right coronary artery which we did with the orbital arctomy followed by two stances uh that's what we did beautiful fantastic results And now here we are to the for this leftsided where there is a disease in the left main additional disease in the LED diagonal and circumfer you want to comment on things.

[00:06:03]>> Yeah. So I mean you can see the [ __ ] track calcium um left main moderate disease uh if you see there um the good thing is seven French and we don't see we can put the hemodynamics we don't see any kind of uh uh heo ventricization >> ventricularization so this is in the circumflex significant this is in the proxal lady diagonal D2 actually large size ostrial disease short but then after that you see a bridge so that is why I um any kind of arthrectomy we do we have to be very cautious that you do not enter the bridge um so this is where we are so I already wired the LED with U a wire and I think this is the kind of case where we know you have to do ethctomy we go directly with arctomy rather than uh imaging >> yeah so let's ask Roberto you have availability with your orbital and rotational uh you have preference to one versus other in this particular ular case with the diffused calcification little bit of angulation and so what would you use in your lab can I ask another even a more fundamental question >> Roberto would this patient in S Paulo go for cardiac surgery >> right 81 >> yes no definitely not he would go to to the cat lab >> excellent approach and particularly if you can get a residual syntax a low residual syntax it's proven that it's absolutely compared to vascularization at 81 we would send to the cat lab but in the hands of Dr. Keiny and Dr. Samin Sharma definitely uh perutaneous >> so Roberto move now to Sam's question how would you tackle it interventionally >> or we just do IVL I mean that's another valid option in these kind of cases >> yeah Dr. There's some question about uh orbital versus rot and uh particularly from the data we have it depends on the operator experience they are similar to each other and from my personal experience I learned with him you don't know but you taught me roablador then but uh there are some advantages by doing orbital because it's a tight lesion and you preserve the flow it's a large vessel you can treat we'll see how deep is the calcium then it's a good case for orbital and similar to IVL IVL may bring a lower complication rate but it's not the case in this >> cat excellent excellent Roberto >> okay so we are ready with the OA the question here is uh Anu has a little doubt whether we use OA versus RA but I think it's okay let's try OA we have taught everybody for in our 205 episodes I'm sure ro had been done in 120 E and so people definitely want to learn a little more of the orbital attack me if there's any question you put this uh wiper wire directly >> okayip you had mentioned about uh >> uh and I've got the majority of the people joining me are at the moment from India where I think uh uh orbital is being launched or it is uh taking up shape so seems a very good idea for uh our audience as well.

[00:09:21]>> Yeah. No actually very interesting as you mentioned uh I started the orbital both places the both continent USA as well as in India you have done many things on two continents >> yes >> actually three because Brazil is included >> thank you so key is the still quite a bit of interest despite the eclipse trial uh the numbers have not gone down in India actually here in America has gone down significantly and uh the key is using this is kind of case you can use orbital. I would say you need to be away from orbital in two situations. One if it is a aotto disease and secondly if it is angulated it's very torturous this because what happen is the wire the we have two types of wire the wiper wire and wiper wire flex. So basically flex goes to this tortuosity otherwise the regular wiper wire which is 012 it cut the vessel in the angulated area in based on the wire position and that's where the concern comes but majority of them can be you know exchange whether do rot versus orbital affectme so in this particular case we thought since we did a great results in with the orbital in the right side so we just use it same one uh one of the People say that you know using orbital then you can go to the large size you can get a better lumen although we rarely used it but in right cornerary I did go to 120,000 RPM uh not only just 80 but 18 a 120 we say 120 should be done in very very selective cases because that is the speed cause a little more dissection and a little more perforation that we learned very early in the use of orbital arctomy >> is uh Andrew still there Yeah, >> good. Okay. So, wiper wire was done direct wiring. With this kind of case, it could be done directly. Otherwise, in a torturous case, you use a a fielder fine cross and uh with a workhorse wire.

[00:11:18]And before going in, we always say now if you can see the top on this uh basically this is the brake release. You put a brake and check the speed. And when you check the speed, it should not be touching the uh towel knowing that yes, it's working good. And the >> then let's start going in >> the slide.

[00:11:39]>> That's a very useful tip. Very useful tip to prepare it.

[00:11:45]>> Roberto, what is happening for calcification in uh Brazil and in Latin America? Is IVL the default or uh is it too expensive? A combination of rotablator and IVL. Roa blader is the leading approach and uh IVL is too expensive. Uh it's very difficult to >> to implement but rot is number one >> 1 mm per second and then >> at Danty Pazanzi we're doing like uh less than 1% >> y >> of the total case.

[00:12:19]Excellent. So orbital is 1 mm per second forward as well as backward because it will ablate the plaque both way and it stops at 25 seconds. It's company made uh the set alarm at the 25 seconds. So when you go forward compared to rota when we do a backward forward here you can do continuously and then 1 mm per second and come back also 1 mm per second uh in order just to get better ablation after you're done maybe two or three times you do because every time it will go into a different area uh of ablating >> of ablating in the vertical axis in the sphere sphere uh so therefore it's a slowly keep going and then Keep coming back. No need to stop. Uh and if you continue, so you'll see that 25 seconds it will make the noise.

[00:13:09]>> Sam mean purely from a conceptual and engineering point of view. A pretty neat device.

[00:13:16]>> I can tell you there is even a better device which is just introduced in India in arc is a 1 mm uh and that has both rotational and orbital based on the speed. uh otherwise a 1 mm bar but that has the diamond coated both proximal as well as distal fully coated uh because roti is not fully coated orital is not fully coated because tip has no diamond chips uh and that has been the what >> I finished >> no do now if it's okay we can do a 120 in this particular case large vessel >> no take a little picture >> collision was significant I would not just do you can do southern French and this 1.25 25 we'll be able to see. So this is a case where I would be okay as long as you have no perforation. Go to the second speed which is 120 uh just one or two times. Uh and so yeah different noise comes.

[00:14:13]>> Yeah. Totally different.

[00:14:14]>> Yeah. Yeah.

[00:14:19]>> Toyota versus Ferrari.

[00:14:31]No, no. I wanted to make one noise of 25 seconds. So the audience can see it makes the noise at 25 seconds. That's a stop and the same speed forward and backward.

[00:14:47]So I mean one of the other advantages is also a single single uh unit single you don't need to change the size >> that's correct and the same way with that 1 mm bar which is done by Mel and >> Mel making this new device makes all the sense you know with all the diamonds which come from Surat.

[00:15:11]>> Okay good.

[00:15:19]Samine also I I I'd like to introduce uh and welcome both France and Gregory to the program and I think it is also in order to congratulate you for becoming the chief of cardiology.

[00:15:32]>> Beautiful. Yes, I would say long many many years of hard work and it's very important that the institution >> only 41 years only 41 years. Incredible.

[00:15:44]>> Yeah. So Samir you can see you know you were talking about physics you see that how this uh orbital ethctomy works. So you really want the effect of orital >> beautiful illustration beautiful. So you really want to the orbital arthrittomy effect you ideally should be 360° calcium because if if you have 180 or less than that that is when you have a risk of this uh you see that the opposite wall when there's no calcium it will actually cause a deep medial injury.

[00:16:15]>> Once again once again Anu a demonstration of what we speak you show it to us so beautifully. What a lovely slide. Perfect. Perfect. So that that is one and you see the physics principle.

[00:16:28]Okay. Why you go with the uh increased speed. So when you go with increased speed you remember it's divided by the radius. When you go with the increased speed the mass is the same but that's when you can you can use it on a larger vessel. The only benefit that you don't need to change the bur size. So increase the speed and then it will uh you know the radius uh will improve. That's is how you are able to get into the larger vessel. That's a benefit. But I think very important is the way orbital arthrectomy works and that the diamonds are both forward and backward. Huh.

[00:17:06]>> So Roberto right here you see the what Dr. Sharma had mentioned at the beginning of the case. Uh a pure educational perspective. Uh we've shown how to use the device. Uh uh its scientific benefits and I will not be surprised. I don't know what Dr. Sharma is going to be talking about but I bet you there would be also academic aspects of uh uh of the trials and what has brought the technology forward. Uh Samin and Anu just outstanding demonstration and I hope it's very helpful to our audiences globally and particularly in India.

[00:17:44]>> Look at you did a great job. Second Andrew, >> can you also show the similar one that we have for rotational arctomy?

[00:17:53]>> Yes.

[00:17:54]>> Excellent.

[00:17:55]>> And Samir Samir uh Dr. Sharma also give us tips and tricks and now they exchanging the wide and uh one question is that the wide the orbital wide is 012 and now he's changing for a 14.

[00:18:09]>> Exactly.

[00:18:09]>> Uh is there Dr. any case you can uh go direct with a stent with the same >> so very good point we had not done it some people have done reason is majority of our you want to imaging >> okay majority of our cases are 80,000 RPM so we always post dilate and this is a large vessel you always want to see because now we have IVL and I always say even for the rot your second bar is IVL rot you step bar almost disappeared and it is the second bar is a IVL >> uh-huh So use a smallest bur whatever you need 1.5 1.25 25 in some cases don't upgrade more complication more trouble after you have made the room IVL is second but now the of course the cost is a big issue so therefore you just go with a non-compliant highpressure balloon and particularly the open double layer balloon works very well although it's still a little more costly uh just to give regular balloons are $65 in America and uh our cutting balloons are about 600 and open NC is about 1,100 >> okay can you >> IVL is 4500 ROA is about 2,000 and orbital about 2600.

[00:19:17]>> Okay. So let's do the imaging then I'll go back to this uh rotational arctomy how it works. Yeah.

[00:19:22]>> Okay. So back >> it's a bridge there. You can see the bridge right?

[00:19:28]>> Yep. Now the eccentric calcium >> you flash flushing >> no left main >> and see if any cuts.

[00:19:40]>> I stop it. Yeah, you can take it out.

[00:19:45]She start of pac not much calcium and vessel size is like three vessel.

[00:19:52]>> No, no. What are you saying? No calcium.

[00:19:54]>> The start of the pu is no calcium. But now coming back >> at the level of the diagonal. Yeah.

[00:19:59]>> Yeah. This is like 180 eccentric calcium and some leavation. The surface might be shaved because the levelation multiple reflection. Here's also very obstructive eccentric calcium.

[00:20:12]Now I see that some blunt. Maybe this is a level of the left uh LED bifocation.

[00:20:17]Now come to the proximal LED. Here's also eccentric like 180 degree of the calcium.

[00:20:24]>> Now what are those multiple cuts? What what's these?

[00:20:27]>> No no they are not I don't think that.

[00:20:30]>> So yeah another point is this is left maination. Now comeoxally this is a distal left main.

[00:20:37]This is of course this is after the uh O but looks like now not that much tight stenosis.

[00:20:44]>> It's still tight.

[00:20:45]>> No tight it's not tight. This the left man is saying is okay >> after O. Yeah.

[00:20:49]>> Now after this >> no no I won't say after O. I think it was okay. Remember we didn't say ventricularization.

[00:20:55]>> Yep.

[00:20:56]>> Roberto what? Yeah. Kishki please complete.

[00:21:00]>> No no no just be short. So no no what I'm trying to tell you is most of it probably was a deep advential calcium right it's 180 so you still in a mild to moderate not severe calcium here >> no no right here 270 plus >> yes >> surface and there's a cut yeah surface is shaved yeah >> no that that's not it's a surface is shaved let's go back okay >> but we are early on we published the in our 40 20 cases of OCT rot versus OA and we found the deep cuts uh with the OA all >> we call it as yeah we used to call it as crater but it's more of medial injury yeah >> put a wire in the diagonal so if you go back to the rotational arctomy slide yeah >> now show the RS slide rotational arctomy you are asking him some questions.

[00:22:06]>> Yeah, I I wanted to wait for you to demonstrate that and uh then go to uh Roberto. The question was regarding uh both at Dante as well as in Brazil and Latin America. What is the use of imaging? Uh what is the philosophy? Are you dedicating it only for very complex situations or uh using it more and more?

[00:22:29]uh following the the recent guidelines and the way image impacts in outcomes uh we are using more and more uh particularly in the complex case where you like this one calcified and uh it's very helpful to to to decide of sizing then it's uh it's been used in Brazil but the reimbursement is not uh allowed in the public area only in the private but uh I believe it's average of 5% of the case >> exactly right Anu you want to talk about that beautiful slide again >> okay so this is the differential the how the rotational arctomy works you see that how rotational arthrectomy works so differential cutting and there is uh you know deflection of the tissue which is very very important mechanism which the way rotational ethctomy works.

[00:23:32]So why this is important is that in like this situation we did not use the imaging beforehand. Okay. In uh I would say less than.5 mm or maybe one or two quadrants is severe calcium. The rest of the area is moderate calcium. In situations like that like I showed you the way the mechanism of orbital ethctomy you need to have severe calcium three quadrant four quadrant calcium for it to orbit and uh do u the mechanism the way orbital ethctomy works but rotational arctomy is deflection of the inelastic tissue like we see there or elastic tissue and the calcium that is there which is being uh you know arctomy oh takes care of it. So for that particular situation even if it's mild calcium moderate calcium moderate calcium does work better.

[00:24:28]So in the bottom line probably if you have a situation probably it is safer to have rotational lethctomy than orbital ethctomy because with orbital ethctomy you got to make sure you have severe calcium.

[00:24:42]>> Wonderful. Okay. So this is a 3.5 20 mm non-compliant balloon. Uh go a few mm more. You just need to go after the diagonal. No, just after. Yeah, just a little diagon. See it >> that we are not in the bridge.

[00:24:56]>> But I think you have to cover the bridge. Bridge has a lesion, right?

[00:25:00]>> Legion significant has a leision. Yeah.

[00:25:03]>> Has dis I don't know. I would go with the >> direct.

[00:25:08]>> Yeah.

[00:25:09]>> Okay. So now question is the strategy.

[00:25:11]Do you want to put a mini crush of the L diagonal or we want to bring it to the left main because there's a circion also there's a significant legion in the circumflex you want to dial it now >> and the diagonal is a pretty large vessel >> no no diagonal we plan was to do mini crush >> then question was for the left main do you double mini crush versus what >> no I don't think left main go back >> oial led is there a lesion in the oiled that is the contributing here >> this is just after lift my verification this is the oiled like They call him >> Exactly. You don't need a big crush.

[00:25:45]>> Yeah, that's the oiled. Oh, good. Very good lumen.

[00:25:48]>> Yeah. And distin is also okay.

[00:25:50]>> If we can show if we can show the imaging again, please.

[00:25:53]>> Okay. Yeah.

[00:25:54]>> Yeah. Show the imaging, please.

[00:25:55]>> Yeah. Perfect. Excellent.

[00:25:57]>> Yeah.

[00:25:57]>> You see the oste area >> 7.4.

[00:26:00]>> Yeah.

[00:26:01]>> That's that's a post.

[00:26:03]>> You can call it a post.

[00:26:06]>> Yes.

[00:26:06]>> Yeah. Okay. And tell us what's your strategy now?

[00:26:11]What do you want?

[00:26:11]>> Let's cut the D mini crush up aium. Then take care of the circ and uh end of the case.

[00:26:17]>> Okay. Get a 2.5 cutting balloon.

[00:26:22]>> Sami. Uh did I make it clear about the >> very clear excellent OA and RA works?

[00:26:29]>> Wonderful. Great illustrations, beautiful slides. Plus your explanation is is top on. uh Roberto a moment uh take us and uh describe to us. I'd like uh people to benefit from uh Brazil has always represented to me uh some of the finest uh uh interventional cardiology some innovations uh uh I have personally uh known and read a lot about Dr. Jateni just to tell our audience he performed the first arterial switch uh for the transposition of the great arteries and the Jateni Foundation oversees Dante Pasani which is a absolute the the greatest interventional cardiology institution and you serve on their board. Uh uh you were telling me that they had something like uh 300 fellows and uh uh a few thousand uh tell us some details.

[00:27:25]Yes, Samir, there is a a large educational program from the from Danty Pazanzi uh in the hostel and we also broadcast a lot of programs from different areas and yes currently there are 300 >> uh fellows in the hospital and it's a 400 beds hospital and 10 cat labs >> and uh the way we we train people and uh we educate them uh is It's very similar to what uh Dr. Charmaine Kini is doing here because we we receive a lot of very complex cases and uh we run some postgraduation program and also we uh accelerate some startups to to teach them how to get into this field of innovation.

[00:28:16]>> Excellent.

[00:28:22]So we can take a 30 or 3.25 48 cover the mid legion. Uh >> I don't think you need 48. 38 should be okay. And 275 to the diag.

[00:28:33]>> Yeah. Yeah.

[00:28:35]>> Roberto that's okay.

[00:28:37]>> We've also had good friends at Dante with Fosto Ferris and Ricardo Costa and uh uh exceptional exceptional work they do.

[00:28:50]Samir is is >> with us right now is watching this case and send the best regards to everybody here and he wants to collaborate with Mount Sai with some international programs.

[00:29:05]>> Fantastic. what we did last RCA >> welcome go synergy >> we've collaborated very closely with many initiatives before including medstream 360 >> we do science >> yeah med was amazing >> I only did 18 to the >> two years ago Dr. Chararma did a life case to the national society.

[00:29:28]>> He treated the calcified left man >> with laser IVL and rot and also cutting balloon in the same case. He did it in 25 minutes >> and created a a huge problem at the interventional community.

[00:29:46]>> He made all of you look so slow.

[00:29:49]>> 38 minutes.

[00:29:50]>> 25 minutes. Yeah. 48. No, but that was a I you know this is I would say one of the case where we are just ready to kind of give up. We used all the material we made that the educational uh case in box.

[00:30:04]>> Yeah.

[00:30:04]>> Superb everything. Why step by step we went into and finally able to do it. And what happened is laser gave us a little room.

[00:30:12]>> Laser didn't cross the oste but just gave us the room and then we are able to put a rot wire and rot wire did the job.

[00:30:18]>> Yes.

[00:30:19]>> So laser didn't go but made enough room because before that no catheter went to the o of the LED. So once a little room we put a a fine cross again and then put a rotar then 1.25 and two five bar and case for the history >> we have to make sure it doesn't come up to the Austrian >> huh >> because you have to do the circ >> Roberto we also would like to you know the as CCC live cases has been expanding globally another area we want to expand is to Latin America and to Brazil and uh we'll probably use your help as well as the help of Solasi >> definitely Ricardo Cost is the current president of Solasi and he's at Dante Pasanz as well and uh I wonder if we could do we start this program by having you in the cat lab in Brazil to launch live CCC through Latin America. We run regular programs across Brazil and we we do a lot of uh transmission as well. Uh >> you you need you need to inspire either Dr. Kiny or Dr. Sharma to take them there and have them uh show their extend their educational abilities to the entire continent. Uh um they've transformed interventional cardiology in so many countries. Uh as Dr. Sharma mentioned uh uh the reach of CCC live uh and you know it's actually not surprising because India and China I think will easily surpass the United States in uh in every aspect both interventional cardiology and structural heart.

[00:32:00]>> Yeah. And actually the Avisad we brought the team to start affiliation both academic and clinical uh talk with Roxar Maran. Uh so that part is uh is still in kind of we are working out.

[00:32:14]>> See I did tell you 40 great pleasure and uh let's uh trigger actually Danty Pazanz is connected they are live and uh following our discussion so false is now pushed to start the program is our brother we did our fellowship together at Dant Pazanzi.

[00:32:35]So we we do a lot of collaborative work with him. He's at the Incor. It's a a wonderful institution in St. Paul as well. We can connect both of them.

[00:32:45]>> I want to go to 38 further. So now we what happened is we selected the long stent. Uh this is the synergy 3048.

[00:32:55]>> Yeah. That's okay. It's going good. See the slowly slowly without pushing the guide. So no dissection.

[00:33:03]Slow slow movement.

[00:33:04]>> Okay. And I think it done the job.

[00:33:06]>> Show me some dye.

[00:33:08]>> Okay.

[00:33:11]>> Yeah.

[00:33:15]>> It'll be very good. Okay. Good. All right.

[00:33:19]>> I don't know. Not I was taking 38.

[00:33:33]Yeah. See we'll have a problem in >> somebody say synergy the dot there >> it doesn't matter >> okay I think just but we have to go to other view >> see it again take a picture >> yeah remember dot is further the stent is inside the dot go back to epic cranial Good.

[00:34:10]Okay.

[00:34:15]>> S mean I'd like to share a lovely story with our audience. Uh >> in 19 >> Some die.

[00:34:23]Some die. Yes. Okay.

[00:34:25]>> Some die first.

[00:34:35]>> Good.

[00:34:36]>> Okay. Good.

[00:34:36]>> Yeah. Ready.

[00:34:37]>> Is this the diag? We're going to the diag now which is 2.75 uh 16 >> 14 atmosphere.

[00:34:58]S mean as you treat this diagonal a quick story for our audience and some of the amazing lessons you learn. Uh >> I my first visit to S. Paulo was in 1993. I had gone to teach laser and the person I was teaching was the director at Incor Dr. Shigamat Shuar. And the day I went to teach him the laser, he had 137 cases scheduled and they used to work 24 hours a day.

[00:35:28]>> That is the power and uh which Dr. Bautello just mentioned which is where Dr. Abizad is at the moment. Uh >> Brazil and its institution of interventional cardiology dates back uh almost as long as ours.

[00:35:45]Absolutely superb. So that's the area of the bridge. So we are just going 10 atmosphere there. There's a calcium at that bridge.

[00:35:55]Usually there's no calcium there soft but uh there could be a lesion but there is a calcium is not expanding low pressure about 13 14 and we have the to post dilate anyway.

[00:36:14]One second. the mid portion.

[00:36:18]>> Yeah. No, that area. Yeah. Exactly. But we post dilate. Yeah.

[00:36:21]>> High pressure. Yeah.

[00:36:22]>> Yeah. Exactly. Because rather than with the balloon, the extent balloon, uh it may cause more uh injury at the edge and dissection. So now we can bring any balloon in the middle which we are 300.

[00:36:34]Get the three. No, we are 3.5 actually.

[00:36:37]Yeah, that's okay. We can 3.5 vessel was 3.5.

[00:36:42]Sharma, do you feel a lack of a mismatch between the ivos and the angel? Because I expected more calcium as we now realize that >> right the big discrepancy here. I would have said everything like a full circle but uh >> it is could be advantial calcium what you're seeing deep advantial calcium looks that way but >> and you can only see that by the OCT where it is otherwise >> no no even >> I learned with you 10 years ago that when you have calcium both sides of the angiogram >> you you don't need image side for preparing >> fantastic okay Ready?

[00:37:27]>> Looking good.

[00:37:28]>> That's the area except that the area I think we should get a 3 0 in that area.

[00:37:34]We have to cross the diagonal. Let's recross it. Uh and uh I would say just with a 3o why don't you dial the o of the diagonal take it out and we open that area of the LED. Samine right time for you to start your uh >> yeah tell us ak what the plan is.

[00:37:52]>> I am not happy the way the di LED looks at the level of the diagram.

[00:37:56]>> No I know that was the calcium and we did the we did go with the orbital until there but now may not have to cross completely. So here is the safety point of view. I think it's reasonable to just go with a short balloon at that level 308 and if it does not do job then we put IVL. I will be safer.

[00:38:16]>> Anu, what were your thoughts about that?

[00:38:20]That how to take >> No, no, no. Look at it. I think what has happened is the thin strut synergy stand. You see that >> probably has recoiled a lot.

[00:38:36]>> Can you see at that level it is? Uh >> yeah. Yeah. Yeah. We I even I was a little concerned when we saw that. Uh I think it'll be fixed by post expansion but uh >> at the level below the diag what did you see on imaging was it >> eentric?

[00:38:51]>> Yeah eccentric calcium >> after the d2 and the other half is pl >> you want 308 I think.

[00:39:02]>> No >> no no here we have to go 202 balloon first.

[00:39:04]>> You want a 308?

[00:39:06]>> Yeah >> or 12?

[00:39:07]>> 12 go. Okay. 302 >> 302 high pressure so we can finish the kiss. 2 or 12.

[00:39:14]>> Um, you want to leave the circle alone because we have so many lectures to finish.

[00:39:19]>> No, no, we'll continue to do the circle.

[00:39:21]He's not coming back third time. There's a very tight circle and we'll try to work through it. Let's take a lot of things. No, no, nothing is >> easy.

[00:39:32]>> Yeah, please.

[00:39:33]>> Oh, no. That is also calcified. Very calcified. Then we have to use IVL. If not rot IVL >> that's what I'm saying. Maybe sometimes they have to come three times.

[00:39:43]>> Yeah, that's okay too. We can bring back for the cir three times. That's no problem.

[00:39:46]>> Yeah.

[00:39:50]>> You want to start your lecture so that we can finish balloon and be done.

[00:39:53]>> No, people sure want to see that legion expansion.

[00:39:58]Ready?

[00:40:00]>> Okay. We are going with the 302.

[00:40:04]That is that area of eccentric calcium.

[00:40:07]Right now I'm at 18 atmosphere. Can you go back to the IS and show me dist to that? Uh >> I thought you would take a 35 level of the D.

[00:40:17]>> No vessel is 30. I mean >> okay.

[00:40:20]>> No no no 35 is the standard region. If you 35 you go 22 atmosphere then you have more trouble and the pharaohs always ask you know I go quarter size lower so we can go much higher pressure. I said that's okay.

[00:40:33]>> 35 at 22 is approaching almost four.

[00:40:36]>> That's right. Yeah.

[00:40:38]Okay. Okay. Okay. This is the area.

[00:40:40]>> Yeah.

[00:40:40]>> Okay. Let's see how much you want to go.

[00:40:43]20.

[00:40:47]>> Is Is that what it is at the level of the D?

[00:40:49]>> Yes, this is this city. Exactly.

[00:40:52]>> This is a place.

[00:40:55]>> Doesn't look bad.

[00:41:03]>> What are you seeing at 6:00? Leave it there and yeah go from >> edge of the calcium and some other plug but it might be some >> hematoma >> maybe because because of the acoustic shadow of the calcium we don't see behind the calcium but there might be and also has some like possible one right before stand >> so we're going with the two to the diag >> yeah first because of those uh calcium and so not left main left main you can still go when you're doing a mini crush that you can go with a big balloon but otherwise these you have to go with a small balloon first because that itself will give a little trouble. Uh and here we can maybe anchor it. Put a LED a little further.

[00:41:50]We have a long room. Yeah. Good. Four atmosphere of six.

[00:41:57]Good. And now we go. Andrew show the anchor.

[00:42:00]>> That was the bridging area.

[00:42:01]>> Yeah, that's the bridge.

[00:42:05]Recross again otherwise 1.512 good >> okay >> good these are the live case third uh tipping point and a lot of tips and tricks that helps interventional cardiologists across the world I wouldn't have used these I just learned So, Roberto, intriguing question for you. I'm glad I got a >> go high pressure, right?

[00:42:40]>> A visitor to our cat lab to ask.

[00:42:42]>> Who do you think is 512 high pressure?

[00:42:46]>> Who do you think are these cases better for the fellows or even people in practice?

[00:42:52]>> I think both of them. The the fellows learn a lot as as I I've been doing over my past 10 years. We we learn a lot. But also as at the end of the session uh you always summarize uh the literature you summarize the evidence base what we are doing it's very good that the the clinicians get access to this uh very important information to benefit their patients. There is a concept of penetration. It's a concern that uh most of the patients don't have access and even their cardiologists are not aware that you can treat such a multile complex patient on a PCI approach. So it's very helpful to both of them.

[00:43:38]>> Excellent. The way you do because you're not only doing the case, you are sharing the evidence behind the decision.

[00:43:46]Beautiful.

[00:43:46]>> So So watch here, Roberto. We've been uh doing this case now for 48 minutes. We started at uh 8:04. uh we have not mentioned any any sponsor any company here and uh that that I think has always been the truth in the message that look learn how to use it and not uh this is not to advertise or to to >> uh mention about the sponsors and uh >> dag always the white side >> if you if you consider that 95% of the innovation come from the stakeholders from the industry. It's uh it's it's impossible to teach without exposing the technology like we just did here.

[00:44:32]>> And once you share the technology for the sake of of the patients, you are doing a good job. You >> need that. Okay. Low to eight. No, no, eight.

[00:44:42]>> Absolutely.

[00:44:43]>> Okay. Both eight.

[00:44:47]>> Both are 12 atmosphere. It's a 3 >> down >> and uh 2.75.

[00:44:53]>> Let's dilate the LED proximal.

[00:44:57]Okay. Go up here. High pressure.

[00:45:01]>> We're going 24 atmosphere here.

[00:45:03]>> Okay. Down.

[00:45:06]>> And we go to >> Okay. Let's do the final imaging.

[00:45:08]>> No. No. Proximal more.

[00:45:11]Yeah.

[00:45:18]Is that area open? No.

[00:45:20]>> Yeah, it is open.

[00:45:21]>> Proximal.

[00:45:22]>> Yes. Yes. Yes.

[00:45:23]>> No. There looks like little dent.

[00:45:25]>> Pull back few mm.

[00:45:28]>> Yeah. Good. I'm going >> outside. We are outside the stent now.

[00:45:30]>> Okay. No, we don't want to be outside the stent.

[00:45:32]>> Yeah, that was outside the st. >> I mean a question to you from an audience in India.

[00:45:37]>> Yeah, >> it's a straightforward answer. But can we do orbital and balloon uncrossable lesions? Yes. Answer to that is yes.

[00:45:46]>> No, >> you can definitely do uh the most there I would say probably the laser takes it but laser is not available everywhere but yes orbital can be done as long as you advance your wire. Uh to me those cases actually do very well with the rotational arc. We have cases where balloon uncrossable. We did try to do orbital arthrectomy and it did not go because what happened is the tip of the orbital does not have a abrasive surface no diamond. So we actually have every year uh now of course we do orbital very little about the 70 cases per month we do of the arctomy orbital makes only three four cases uh majority are the rotational arctomy and about 67 the ledger was uncrossable legion which you just mentioned uh so orbital in the past we used to when doing a 25 30 orbitals we used to get at least two to three cases per year uh where orbital will not go even in a you know it's a tight wrong legion because of the tip it just keeps coming back and then we change it to 1.25 and 25 bar after the rotab bar and case is done right away. Uh so that's that will be the I would say the difference which we have seen. Uh now then to answer that we made the micro crown. The micro crown only thing the engineer made not a continuous from the tip. They made a small about 3 mm at the tip abrasion surface then there's a gap and that was the same the rest of your regular crown. So there was a gap. So we did a trial with ourselves and in Japan.

[00:47:20]So we found that 4% of cases the it twisted in between you have the abrasive surface no surface then abrasive surface the cat used to turn twist in that area so they took it out so orbital team took that out completely no longer available now but that was a micro crown >> nice landing zone >> but that was not a full concept you had to have all throughout a bridge surface you cannot interruption in the middle >> learn very well one question regarding the provisional approach Uh some people in Brazil are not that reluctant to to use rot after a small dissection.

[00:47:56]>> Would you do rot after dissection?

[00:48:00]>> Well, I mean you want to avoid in that particular case. If you did a balloon and you see a bad dissection, you should avoid rotational arctomy or if patient stable, let it go and come back in a while. Uh but now if you can get that case push with the IVL that's another way. Uh but yes, you're right. If you see a obvious dissection, our threshold of doing roti is very very high.

[00:48:21]>> Maybe just to the failure if you cannot do >> after this is oial leion.

[00:48:25]>> This is after D2 eccentric shape after more than 5.5. This is after D2.

[00:48:31]>> Okay.

[00:48:31]>> Now coming to the proximal here is like more than 10 expanded >> nicely >> proximal edge. Yeah. Go back there.

[00:48:39]Right there. Right there. Yeah.

[00:48:40]>> Yeah. This is a proximal on the plug with normal position. No dction area is open. Nicely placed.

[00:48:46]>> Yeah. Well expanded.

[00:48:49]>> Water is well positioned.

[00:48:51]>> Another question uh from the audience.

[00:48:53]Uh you've kind of addressed it towards the beginning. When will we see back burring rotor?

[00:49:00]>> Yeah. So very important. and I actually have taken a two trips to uh their plant in Minnesota and we have done we actually have the uh the bur with a totally fully uh that a bridge surface backward and forward and I we did a you know experiment in the the in vitro and point happened the 1.25 25 bar it still got stuck >> others did good so therefore now they're going back to the drawing board I said that's the biggest culprit so they we are supposed to go maybe in next few months and try to look into it that what can be done but yes I would say uh probably uh for the trial point of view maybe by end before end of this year they may do a a feasibility study of 50 cases and so and they're already working with the FDA to submit that but yes we'll have it very soon >> excellent looks Eight.

[00:49:56]>> Wow.

[00:49:57]>> No. Good. And left man was not bad on the >> again. We confirmed that like 10:00.

[00:50:05]>> Good. So, let's >> quickly change your patient. We can do another case when he's doing his uh >> No, but you will be talking there. So, let's go to our uh presentation. Now, this is excellent uh demonstration of the another will be a third stage. Not bad in this particular case. 81 year old come back with a calcium with you see the circumflex also very calcified and that was our plan which we did and mini crisis stenting we just did not had a time to go our o criteria which we always do in this particular case will fall into the lmca disease on the left although turns out to be not much LMCA disease on the imaging but angographically was clearly 50 60% a little bit of bifurcation so it by criteria Originally when you say it's rarely appropriate which in the past you used to call inappropriate but this particular case has a hard team discussion even surgeon at age of 80 plus are very reluctant so I would say it become a after the hard team discussion with that note very we actually have a the two uh interventional publications which is about the the DCB which is taking the center stage uh two trials solution uh ISR R and solution D novo and then Anu will talk about the yellow three studies of evoluc in maximum statin therapy in chronic coronary disease because his heart that intracoring and transcrytoic characteristics before and after maximum lipid loading therapy with the yellow series of uh studies which have taught us quite a bit over last 10 years so simply the two of them I'm going to go through solution for ISR this is the first trial remember agent trial was approved based on they compare the DCB the packly texture reluting stand compared against the balloon angoplasty but what is the class one recommendation uh for for DSR either you do a reads or you do a drug coded balloon so therefore they still allowed it and that led to approval of the device which is fine so when we organized this solution ISR I was in the steering committee that does not make sense you had to go against the redes and this is where we say okay still we have to answer so 80% where the two arm that patient either get the redes or balloon so what happened is the balloon angoplastic group was very quickly done then of course redes take little time but all the cases were done whether one or more than one layer of stent so this is a solution uh and how the whole question you know the pact has been there for 15 20 years because of lipohilic and it's not a lipophilic agent with the with the serum and Therefore they had to do a lot of work in terms of the micro reservoirs as shown here and then have the biodegradable polymer and then a special proprietary phospholipid coating. So key is that so that drug stays there. So very important is you can put any drug on any st any balloon but how much it goes into the vessel wall the transfer efficiency is the key and this is where after the initial work and we know that now we have the uh the magic magical uh the dirt coded balloon has been there for quite a while in India but here in United States about four five years ago they started with the solution trials in the initially ISR then small vessel and we have been part of them and we have been lead enroller uh in the trials. So just to say that this was a trial of the solution for ISR with the 210 cases in the DCB DEB group or 28 with a control group and basically basically regular technique wise uh was done and in the control group uh about 2% of patients uh the as you said DB against control and control 80% 80% of the patient have a stent and the DB group 1.8% 8% had a bailout extending and that led to these results. The DB and control identical DB slightly went higher numerically you can see but no P value significance uh even legion thrombosis was no difference and at one year uh integer points is very interesting what they wanted to say you know subgroup they also wanted to know that what happened that 80% dees group uh redes versus balloon angoplasty and you can see here which I made it important that once you have a balloon angoplasty against the DB did great. See the favors the DB. But when that 80% group you take of the all trial the 80% of those patients which were got the D deb failed.

[00:54:46]So answer they came with the two no negative two negatives which you can figure that out that that the DB was not non-inferior not to say the inferior was not non-inferior to DES. So clearly we know that once a dees DB not the answer and this is basically was there second uh so question is what is going to happen DCB will not replace the dees instead their value may be in expanding the therapeutic toolbox for ISR providing option to treat resinosis while preserving the vessel for the future key is what we learn also that by doing the DCB you or DB you didn't penalize the patient patient still have may come back with ISR but didn't have did not have more MI didn't die. So therefore it's okay you want to avoid the metal give it a second chance for other technique in the future. Uh and this is as I said first enrolled cases we did uh here at Mount Sinai both for the DNO as well as for the ISR and we were the lead enroller as I said with the 63 patients in this trial. Second was solution doova which was done multic-enter Europe trial not to the United States because we are United State trial still ongoing with the solution denovo studies small vessel there we took all the patients with denovo coronary lesion small large and so open label of course and large number of patients close to 4,000 and pro procedial statistics and so which I have put it here nothing different they allowed to do even rotationctomy of course The specialty balloons was used almost in 30 40% of cases which happens and the and the more important people will ask that yes what was the number of using the stent in the uh in your DB arm same thing what happened about uh 2% or so now individual end points as you can see primary endpoint of the target vessel failure which is the T MI revascularization as a death was identical slightly dees favorite but Otherwise no difference the target vessel revascularization also about 1.2% in favor of the DES. So you can say based on this I think both are okay but DS definitely have a small advantage and the the these are the individual end points you can see again the height of the our drug quoted balloons the compared to the DES is higher in most of the categories and very important of these 2 3600 or 33 400 patient then these are the intention to treat because they use the cases what's complex bifur application which are not part of the original trial. So they went to the per protocol and guess what interesting happened per protocol analysis of the 3194 patients showed one year target vessel failure rate of 5.2 in in cerolumus group and DS group was 4.1 the risk difference was 1.09 09 they did not meet the criteria for non-inferiority that basically means it was inferior in the per protocol cases so this is whole question so and that's why when they came to America uh and these are the individual things large and small vessel slight favor of the DS and the small large vessels and so so therefore in the United States at present same trial is going on solution DO we are I think now second or third because we have so many DCB trials uh but it's ongoing once it is done we'll really answer the question in the small vessel large vessel will not be shown by the American US trial because they are not the part of the equation so with that note this we continue uh to really say and they put it very nicely as you can see at one year the primary intention to treat analysis analysis a strategy of PCI using serumous eluting balloon and provisional dees were non-inferior to the systematic use of dees for primary endpoint point of target vessel failure but the per protocol population sensitive analysis did not confirm non-inferiority that basically to me it was inferior as we know with clinically driven TVR occur more frequently in the SCB strategy group at 5 year what they're saying is the one year is one year but we are saying that not putting a stent is a long-term benefit and this is the second secondary end point of this trial will be five year data Uh so with that note I now invite ask Anu to present her series of uh yellow trials and she has put her uh lot of time many years uh into teaching us in the various aspect of the yellow uh in uh var and various publications. So Ano she the first one will start with the yellow three which latest came out in the imaging uh in the jack imaging.

[00:59:37]>> Yeah. So no we're not we're not starting with yellow three. we got to start from the entire yellow family of studies that uh we actually did here in Mount Si. So the important question why we started was uh you know when patients come to see you despite uh good medical therapy man good uh cholesterol uh management they still have new lesion formation so the question is doc what do I do? So one new lesions could be obstructive new lesions could be nonobstructive. So we need to answer both of them and the question is how we prevent uh progression and induce regression. A very difficult topic but I think uh we'll try to answer as much as possible.

[01:00:21]So the whole yellow three yellow one yellow 2 yellow three you see here from 2010 to 2024 actually the yellow three just got published uh this year. So the first in 2012 and over the years medications have changed, therapy has changed, guidelines have changed, imaging has changed, lot of things have changed. So we were trying to incorporate and understand exactly what happens in the coronary arteries. The first question was that do statin really work and if statin works do you need the intense therapy? Because at those days guidelines uh therapy was not uh to what we are right now. So we randomized standard of care all kinds of stratin to rosa stratin which was uh you know at that time initially introduced. The only thing was we checked the lesions of 6 to 8 weeks. What we did was we took patients with obstructive disease and wanted to see by giving statin will it change. So obstruction was that patient had to have FFR of less than.8. So that was uh yellow one two and three. So let's go individually. So uh to understand that we had to image we did both intravascular uh ultrasound and we used what is called as near which tells us uh what lipid is so total of 87 patients stand of care aggressive therapy patients had to have ffr less than.8 eight. Um so once that was done when they came back we repeated all the imaging. So interesting of course with highdose statin you see a cholesterol LDL everything changes and since it was only 6 to 8 weeks we saw some change in plaque burden but increase in FFR essentially trying to say that the plaque regress with FFR improvement which means you don't need to stand the patient that we saw some uh trend but we never saw P value because one the numbers could be low and that the you know the number of weeks we treated probably less but um not now. In the future we are going to show you some stud some uh sub studies of yellow three where we are showing that definitely there is a change in the vessel wall physiology when the lipid changes. So this is what we showed that LCBI definitely decreased with aggressive therapy. This was a case example where you see uh FFR 74 became 78 change in LCBI but what we saw was the change in the LCBI which is on the right hand side you see that third tal is that majority of the larger the LCBI the bigger the change we saw in the patient so as and the group I would say of 30% of the patient since they were all comers we did not see uh any lipids um in this patient so if you take the patient at End stage atherosclerosis most of it you will see calcium maybe you'll not see lot of lipid so you need some lipid or essentially we're trying to say get the patient early on in the disease process so what did we learn from yellow one that aggressive statin works and greater the LCBI that's when you see big change so now what happened is if we want to go to yellow two one you have to make sure there's lipid before you enroll the patients and say that okay there is some change in the etherosclerotica plaque and we wanted to understand how exactly the changes and by that time optical coherence tomography was introduced we could see what's called as a fibrous gap these changes happen exactly how does these changes happen what we know is the HDL functionality so this is where I think when patients are coming to see you in the office we tell them okay yes your LDL change LDL change no is talking about HDL HDL here also is very important important and HDL has a certain function which is called as a cholesterol elux. So let us go a little bit to the basics of what we learned in biochemistry and our early part of uh our medical school. So you see that the entire cholesterol mechanism happens between the intestine where triglycerides come in as kyomicron go to extraatic tissue inside the liver in the liver there is extra formation of cholesterol. we will I will go through some of the steps of the cholesterol mechanism and the whole process goes on.

[01:04:42]So body has a nature has created a homeostatic mechanism. So this homeostasis has to be maintained. So if you see uh the HDL which is extrapatic tissue the important part what HDL does is reverse cholesterol transfer. it takes from the hypatic tissue um sorry extraatic tissue back into the liver and that's where it gets so this is uh I think something we need to uh learn also is that LDL you see that majority of the LDL which is LDL LDL VLDL or that we showed in that uh hippatic uh mechanism they which has a B okay these are etherogenic red okay but when it HDL which is EPO AA it is ethroprotective.

[01:05:33]So very important I think we will hear this and patients will ask you this question what is EPO B what is EPO A? So EPO A so like I always say if you are a A+ you're good in life when you become B+ you're bad. So just remember that way a is good B is bad and then little A is also bad. So that will be another lecture by itself but just for you to know that uh these are something that we need to understand. So very clear uh you are on the left side which is your uh flow in inflammation ethogenic which is anti- everything and the red if your balance is good you have a healthy vessel. Healthy vessel is a vessel that moves and no pluck. when there is for whatever reason the balance imbalance happens the homeostasis mechanism of what I showed you between intestra and extrapatic tissue changes you start forming the plaque and why I'm going through this is when you talk about these things that's important what why how this lipid moves from everywhere you have to understand macrofasages and I will tell you why because this is also we found in uh yellow so macrofase M1 is pro-inflammatory not good. Okay. M2 is anti-inflammatory.

[01:06:54]Fagocytosis removes the cholesterol. So you you need M2 macrofase. You understand? So just remember that M2 macrofase is good in life. And the most important thing which we found is that mitochondria. Mitochondria is the powerhouse. Mitochondria is required for everything in our body and that is what you will see mitochondria um in the entire of the process. So this is going back to how exactly the plaque is formed. I showed you what a normal vessel should look like. What an abdominal vessel will become. So how does it happen? When you have a lot of LDL which you see there gets into the vessel wall. This macrofase which is M1 M2 goes there takes it out and it forms you know form cell when lot of go happens epoptoastic cell happens. So but that's also called as epherosytosis. If your macrofase is a good macrofase, it will uh take away all the cholesterol.

[01:07:52]So if you see that the macrofase there from there the HDL takes with the along with EPO A1 and goes back to the extra tissues. So you need what is called as epopasis should happen. Ephroyto should happen. So this is what is called as the how HDL works. It is reverse cholesterol transfer takes the cholesterol from the tissue means plaque into the liver. So very important that is how plaque changes. So on the macrofase there are what is called as certain receptor ABCA1 ABCA2. So these should be functioning so that your cholesterol is taken out. HDL should work through that. So very important this happens. So going back to where statin works. Stratin works as as a HMG co-ed reductase which is the rate limiting step in cholesterol formation of the liver. So another important question the patient asks should I take a statin or should I do lifestyle modification not eating uh cholesterol.

[01:08:56]So that is where you need to do a testing to understand what is problem with that patient. But if it is something that's the genetically forming lot of cholesterol statin does work and very important is more other steps are important because in cholesterol synthesis which starts what is called as through a melonetic pathway there are two enzymes which is SL uh sorry SQL as well as a DHR you'll see that and these are the enzymes and we will show that they are see were important uh upregulation in yellow too Having known how this thing happens, we went embarking into yellow two. One, you have to image. Two, you have to understand how the cholesterol is removed. So you have to understand that the HDL functionality is working. HDL is doing its job which is cholesterol elux.

[01:09:48]Does that happen? Why does it happen in few patient? Why does it happen in few other patient? That is why we had to understand the genetic profiling. So you got to understand how the gene is. So everybody comes with the DNA. DNA is then translated becomes mRNA. mRNA then becomes a protein and that is how you will check that in the blood. We check the mRNA. So going back to our yellow two, we checked cholesterol e-lux. So we did all the essays in these patients. So the patients came they had uh you know lesions we did OCT we uh checked their uh uh nears and we was given rosoastratin. So when they came back what did we find? Of course LDL change.

[01:10:35]Remember I said B is bad A is good. So B went down A went up. So I think statin was doing a good thing and uh CRP of course will uh decrease when you use uh the statin and cholesterol e-lux capacity which is CC if you see that definitely improved in this patient.

[01:10:57]Essentially all the mechanism that we thought how the cholesterol removes from the plaque was working in this patient when they got the statin. So this is cap by doing so cap thickness increased in these patients. So if you go to what exactly changed or why the cap increased in these patients two things were important. Patients who had a good cholesterol e-lux capacity their cap improved and that in fact reflected by decrease in inflammation or change in the HCP. Now I showed you the enzymes that were responsible for cholesterol mechanism which is uh SQL DH CR24.

[01:11:39]So these were the enzymes change which means the statin was working through that pathway. Another important is those uh ABCA1 ABCA2 you know the receptors on the macrofase which I showed which works in cholesterol reflux that also uh there were changes in this patient. So essentially telling that the mechanism what we knew works in this patient. This was the central figure and this was again the intravascular imaging of the similar paper that we had shown uh we had did at those days we used machine learning model to see who would respond and who would not respond to statin because we still know there are few non-responders. So what we found was there were certain important uh patients they had certain genetic uh predisposing markers where who did not respond to statin we do have their genetic um uh you know profiling which we will use uh for the future to use them. So LO2 what we studied that you need there are statin non-responders so you need aggressive lipid lowerings by then new drug PCSK9 came into existence maybe longer duration because this also was uh 8 to 12 weeks and then of course enrollment was based on OCT thinning. So we are just showing how each medication works. By then we had a PCSK9 which was evaluab and of course incleran also came into ex existence. We use a luccomab. So this was yellow three longer duration. We used uh OCT lipid arc as uh the enrollment criteria. All patients had to be starting. By now we know everybody has to be on statin and then you do aggressive therapy by giving evolucab.

[01:13:30]So we did again genetic uh profiling.

[01:13:33]Here we did a transcriptto. It's a different technique by using bulk RNA.

[01:13:38]Bulk RNA means you take all the cells and you analyze them rather than doing single cell. Single cell is very important so that you will understand the various cells that we described which cell works. But that would be the next step. So you see that fibrous cap improved and LCBI decrease. So what did we show? If you see that in these patients uh example fibrous cap was 60 improved to 90 LCBI was 782 became 285 and some change in the IUIS. So what we found was even in this patient who had statin who got a mapab about 80% fibrous cap improved we call the fibroscap responders and some of them LCBI decreased which we called as LCBI responders. So there's a term we call this now a melting butter sign. The butter that is in the artery is melting.

[01:14:32]So this term has been coined and 20% we saw was nonresponders. So very important everybody has to learn. Look at the LDL on this patient 78 at baseline came back LDL of 7 fibrous cap 5050 LCBI same. So what we're trying to say is we are seeing the patients in the office. We are looking at their LDL and you're saying hey you're doing a great job.

[01:14:56]Patient comes back with new lesion comes back with MI. Okay. So there is this 20% patient and we don't know why why this is happening in these patients and that is what we found out. So this is a central figure that just got published uh this year in 2026 the melting butter sign which we have shown there. So the question is was the response both uh responders non-responders similar to total cholesterol and LDL? Yes, similar.

[01:15:26]So what did we find? So we know that there are 20% who are not responding. Is there something in their gene that is telling us why they are not responding?

[01:15:36]So this is the bulk uh genetic uh analysis that we had seen. So you take all the genes then you put them through what a special pathway they have created. what is called as engineerative pathway and in the pathway it will tell you these genes are responsible for this particular pathway of the body. So what did we find there was upregulation of what is called as uh ATP synthesis oxidative phosphorulation and more important is mitochondrial translation which is responsible for protein synthesis cell response to stress. So mitochondria is the key I showed you how important mitochondria is. So there was a down reggulation of mitochondrial dysfunction, down reggulation of cell surface interaction with vascular wall which is important how the cells get stick to the vessel wall when there's a lot of uh uh cholesterol. So down reggulation of the bad bad pathways upregulation of the good pathways that's what we found. So going back to can we differentiate responders non-responders.

[01:16:42]So that's where we are. Responders had good mitochondrial function, good cellular response to stress and that was responsible for protein synthesis.

[01:16:50]Non-responders everything mean mitochondrial function did not change.

[01:16:56]So mitochondria is important and this is what we had found in the theme. Now when the patient is coming to see you in the office can we understand is there something what is called as a baseline gene that will predict who responds and non-response yes so fibrous cap thickness change based on the ba baseline gene we had found some baseline genes same thing for LCBI change there are some baseline genes saying that if you have this baseline good genes you are a responder so what did we find yellow three that comprehensive assessment of mitochondrial function is a key everything else I have mentioned so mitochondrial function mitochondrial function mitochondrial function and other thing we want to do is single cell RNA rather than the bulk RNA to understand exactly which cell line is responsible to change so this actually as soon as I presented in uh uh HA I had shown this um whatever I Just spoke is the same thing that is available that we made a nice animation with help of Andrew and Ulia. You see how uh you know the monocy goes in changes into macrofase macrofase inflammation goes up starts eating all the lipids and inside the macrofase is a mitochondria. So when mitochondria gets overworked this is what is called as reactive oxygen species which is not good. You cannot have reactive oxygen species equal to red. You do not want that. Okay. So you know cell death more lipid comes in plaque is formed. Um so you see that cap becomes thin thin thin and there's a risk of rupture. When you give a look map everything reverses and things get better. So you see that that is what the cell is not adhering anymore to the cell wall. That's what we had shown and mitochondria start functioning. If you see that everything gets better. So what actually we showed was that what we saw in the genetic changes we saw genetic changes in the phenotypic changes and this is the first time somebody actually that we showed that genetic changes is equal to phenotypic changes that we have seen. So going back mitochondria is the center. Mitochondria are responsible for elux. Mitochondria are responsible for anti-inflammatory as well as mitochondria responsible for ephroytosis and other parts of uh um you know macrofase functioning. Bad mitochondria you get aththerosclerosis for. So the two things we are promoting melting butter and healthy mitochondria.

[01:19:43]You need a healthy mitochondria for survival as well as living. So how can we get healthy mitochondria? No definite dis I mean medication has been created but is there something we can do?

[01:19:54]Definitely dietary intervention. If you see here good diet which is often Mediterranean diet restriction gives you healthy mitochondria nice ATP formation. The American western diet which you see there is bad dysfunctional mitochondria.

[01:20:12]So you can change your diet and get healthy mitochondria. So that is what I promote red juice, beet juice, green juice. Okay. Yes. Yes. That promotes healthy mitochondria. That will be another lecture of what is good food and how to remain energetic your entire life. And this has been proven and pro shown that exercise improves mitochondria. Very important. So this is something everybody can do that you can exercise. That is why this tri showed that overall this data support notion that long-term engagement in multiple type of physical activity help extend lifespan. So you know exercise and physical activity is part of the guidelines which is very important. They actually increased it. The ESC increased used to be 150 they made 150 to 300 of uh um physical activity of moderate and a high intensity is 75 to 150 that is where we are. So this is a yellow three done and we learned that just by doing mitochondria is not enough. I think we need to go to next level which is proteomics metabolomics and that way we'll get a biomarker. So when the patient comes to see you in the office you can do a biomarker and say responder nonresponder and start the treatment.

[01:21:29]Meanwhile lifestyle modification is very important. So yellow four we are going to start where we're going to use transcrytoic metabolomics and special testing to understand the patient's mitochondria. Uh so there are special tests for that. So this is just the take-home messages which we have gone through all of them. So yellow three is there is non-responders we need mitochondrial recovery inflammation resolution and this gives rise to what is called as personalized prediction.

[01:22:02]So future is in the past you take 15 20 30 years to find a drug. Hopefully with the current uh AIdriven uh drug development we should be able to get a drug towards mitochondria. So when the patient comes to see you in the office do the blood test, biomarker use the AI model to understand exactly what kind of medication and what kind of uh you know uh exercise regime this patient can leading to what is called as a personalized treatment for CAD. This is the future and this is what we are going to coin and all that I've discussed right now is available on yellowotrials.com and these are the various publications and more. This year itself we have had about six publications from yellow and uh the substudy of the yellow 3. So that's where we are with that. Anu remarkable presentations uh I think uh one of the best ever in the 17 years we've been doing CCC live cases it is the past present future your life's academic work for the last uh almost two decades congratulations and such a relevant presentation to everything beyond all the catheter manipulation this is the foundation where we need to focus >> you want to talk so the final if you See here this was a beautiful editorial written by uh uh Faruk Jaffar. Um so if you see here in conclusion Kiny Atal are to be congratulated for leveraging clinical imaging and transcrytoics to the further understanding PCSK9 inhibitor responsiveness in clinical population. Based on this integrated framework we may be witnessing the down of personalized medicine for CAD pharmarmacotherrapeutics. It's unbelievable.

[01:23:54]>> I think that is exactly what I had said it without the editorial.

[01:23:58]Fantastic work.

[01:24:00]>> Yeah. Completed now. Beautiful. Just quickly finish it. So we always go through our serumous D deb similar to usual care in DSR with predominantly redes. I put only one but also negative because we learned that only the if you go against that redes it failed. Second uh the serumous eluting balloon PCI similar to systematic systemic DS used in denovo legions for target vessel failure. This was one trial and of course we are talking about the single center trial of the CCD intravascular imaging with a PCSK9 inhibitor therapy showed lot of things for us. So besides just decreasing the LDL decrease inflammation mitochondrial function oxidative stress all those. So now we can kind of predict the reason why patients are not responding and so. So quickly our three questions following are the true statement regarding the results of the solution for ISR trial comparing serum soluting balloon versus standard of care for DSR except similar TVF similar legion thrombosis similar uh ACB superior to balloon angop angoplasty assignment arm. SB similar to REDS assignment arm and similar MI rates in the both group clearly was it was not in the REDS assignment it lost to REDS uh serum eluting stent in our solution four trial. Then the randomized comparison of the solution the serolimus eluting balloon versus systematic DES all denovo legion showed similar target reser failure between two cerolumus eluting balloon was not non-inferior to DS in in protocol per protocol analysis patient similar cardiac death rates with SCB versus DES group lower MI rates in the solomus luting balloon versus DS group and similar legion thrombosis between two groups so it was could not show we could not show that it was not non-inferior. It looks like it was inferior but the word they used it was could not show that it was not non-inferior. Uh and then finally that's why we did a small vessel trial ongoing in the United States. Following are the true statement regarding the intraordinary imaging of the yellow three trial of maximum lipid lowering therapy except follow-up duration of the trial was 26 weeks. OC showed fibers cap thickness of less than 65 micron in majority almost 50% patient showed no reduction in the lipid core burden index minimal fibers cap thickness rose more than 27 micron from baseline to followup and analysis showed restored mitochondrial function in majority clearly it was not the 50% it was six whether whatever we take it the 20% around 20% were nonresponder not 50% with that note with the extensive teaching of the yellow concept and very complex case done uh beautifully with the uh the change strategy but show the orbital arctomy to be done safely uh was the hallmark uh of the today's presentation Sam always much to learn from you stay there on that picture this is the art of uh wearing the tie uh with the with the lead so all preserved there Anu beautiful case great presentation ation. I think it is appropriate for me to read exactly a note which I have just received. This is coming to us from Dr. Fosto Feres who's a dear friend possibly the best educator in the entire Latin America. He's the chief of cardiology at uh Dante Pasanis. He has been watching the entire broadcast. He says uh the live broadcast was spectacular, excellent teaching and a brilliantly demonstrated technique. Congratulations to you all. So uh I think that sums it up beautifully. I'd like to thank Dr. Roberto Bautello for joining me. Anu, great presentation, great case. We stop here and we'll join you on August the 18th.

[01:28:06]>> No, no, no. Little change. August August uh 24th.

[01:28:12]>> Okay. 25th.

[01:28:14]>> I'm glad we are stating that.

[01:28:17]>> Yeah. 25. August 25th.

[01:28:19]>> August 25th.

[01:28:20]>> Excellent. That would be the next case.

[01:28:23]>> We'll we'll send that announcement. Put it on the website. Roberto, thank you for joining us. Anu, great case.

[01:28:30]Excellent presentation. Okay, it was good of