Talking Tall Rounds: Contemporary Evaluation and Management of Stable Coronary Artery Disease

Podcast Transcript

Announcer:

Welcome to the Talking Tall Rounds series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Faisal Bakaeen, MD:

Morning. Thank you for joining us this morning. Tall Rounds entitled Contemporary Evaluation and Management of Stable Coronary Artery Disease. There's been lots of discussions about how to manage stable coronary artery disease with guidelines, contestation of guidelines, and the cases are getting more and more complex, so we thought this would be a good opportunity to talk about it and update you and reflect the way that the team at the Cleveland Clinic manages those cases on a day-to-day basis. We are going to start with his presentation.

Amit Goyal, MD:

This is a gentleman approximately 50 years in age who was presented with stable angina, and he was referred for bilateral mammary CABG evaluation. At baseline, he has class two angina and stress echo recently showed preserved LV ejection fraction with inferior wall hypokinesis. His left heart cath on the outside hospital, the report indicates RCA CTO with severe LAD stenosis. Medical history is notable for diabetes, hypertension, hyperlipidemia, and family history of premature atherosclerosis. Indeed, the still frames from the outside cath show a proximal RCA CTO supplied distally by left or right collaterals from several perforators and what was noted to be severe stenosis in the LAD, on closer inspection, may be in the intermediate range.

Amit Goyal, MD:

The SYNTAX II Score was developed as an anatomic and clinical criterion to help guide revascularization strategy in patients with multi-vessel disease, and our patient's score indicates equipoise for surgical versus percutaneous revascularization. In concert with a hard team decision, PCI was offered. The score was validated with the use of state-of-the-art PCI, including physiology-guided intervention, contemporary stents, and post-PCI IVUS for stent optimization. The decision tree for physiology-driven revascularization includes deferral of PCI for iFR greater than 0.93 and FFR for iFR in the gray zone was 0.86 to 0.93. LAD iFR for our patient across the lesion was 0.92 in the gray zone, but of course nothing is so simple. The LAD supplies collateral flow to the RCA said another way. The LAD, the donor vessel, experiences coronary steal to the RCA territory the recipient vessel. In such cases, CTO PCI may improve the hemodynamic flow in the donor vessel.

Amit Goyal, MD:

And so, the patient underwent CTO PCI of the RCA. The CTO was crossed with parallel wiring. The patient also underwent distal RCA PCI for complete revascularization. The PL system here was crossed using a backwards hairpin technique. After CTO and bifurcation stenting, IVUS showed optimal stent edges, stent expansion and apposition. Here's the final result. And following successful CTO RCA PCI, LAD iFR improved from 0.92 to 0.96 or solidly negative. Here's an example of complete percutaneous revascularization for a patient who's referred for bilateral mammary CABG following single-vessel PCI.

Wael Jaber, MD:

So again, I just wanted this morning to reaffirm what Venu just talked about and try to figure out where we are right now in 2022, looking for 2023, in terms of guidelines for stable coronary artery disease. These are my tasks for the next six, seven minutes, is first to define what's stable CAD. I think we have not yet arrived at definition this morning. Advances in optimal medical therapy, lessons from mostly ISCHEMIA, predominantly CLARIFY registry that Venu mentioned earlier and discounting the low-event rates in the modern trial. When we practice every day, we discount these trials and we say, okay, we'll still do what we've been doing for 10, 15, 20, probably 30 years, and focus on death and quality of life for these patients.

Wael Jaber, MD:

First, let's start with the definitions. I couldn't find any American definitions for what's stable coronary artery disease, but this is from the Japanese Society of Cardiology, just came out this year, and they define them as type one, two, three, and four. You can see here type one and type four in red with patients with suspected CAD with stable angina and symptoms and dyspnea. These were covered in ISCHEMIA trial. In type four, the asymptomatic subjects in whom CAD was detected by screening, and these were also covered in the ISCHEMIA trial. What was not covered in the ISCHEMIA trial were the type two with new onset heart failure, and I think this would be a subcategory of stable CAD that we should consider higher risk. And type three which are asymptomatic patients or symptomatic patients more than one year after an event or revascularization. Again, ISCHEMIA covered type one and type four.

Wael Jaber, MD:

Now, the ESC came with some definition in 2019, but mind you, these definitions came before the ISCHEMIA trial and before the CLARIFY registry. So automatically, when they came out in 2019, they became outdated almost because of ISCHEMIA and CLARIFY, and so they give a long laundry list, and I'm not going to read it for you right now because we have no time for what is stable CAD. And I think the ACC and the next guidelines coming out next year for stable CAD will have their own definitions too.

In addition, the ESC gave us a pathway of how to treat these patients, and I'm sure Dr. Ruthmann will go over it in the next lecture. But what we have here now, we have some actual path for most physicians of how to treat these patients and what's an initial therapy and what's a complementary therapy going down with these patients. And then, they gave us some nice graphics of which patients should be revascularized and how we should consider revascularization. As I looked through this, I found that, to please the surgeons, almost everybody at the end ends up with revascularization, in addition to medical therapy. No matter what, if your stress test is normal, abnormal, you can see here the arrows point to revascularization.

Wael Jaber, MD:

Now, as I told you before, we have some updates, especially after ISCHEMIA and CLARIFY. And I think as a community, we should respond better to these than just keep doing what we've been doing before and hope for the best. So, this is what we have right now, and this is the paradigm that was created by ISCHEMIA right here in the middle. Of course, you have patients with LV dysfunction, which we don't have any idea how to treat from clinical trials. We still use clinical judgment for these patients and patients with refractory symptoms and how to address these patients specifically if they have no proven ischemia on stress testing or invasive assessment.

Wael Jaber, MD:

Now, to start with ISCHEMIA, I'm going to show you only two slides from ISCHEMIA. You can see here the event rate. Even death was very low. Fatal MI was about 1 percent per year. No matter how you slice this, which population you represent, which group. With CKD and without CKD, women, center is geographically different, the event rate was very low in this population. And most of the death if you look at them were non-cardiovascular death. And that's our clinical experience right now if you follow these patients with stable CAD, unfortunately, they die from other reasons besides cardiovascular disease.

And which patients will benefit from revascularization or invasive strategy? And I think this is something in the future we should adopt in our practice, which is the Seattle Angina Questionnaire, which we do not adopt routinely in our practice. What we have here is these are patients here who have more frequency of angina right here. And you can see at least at three months and 12 months up to 24 months, most of these patients will benefit from revascularization in terms of angina relief versus patients here who have very infrequent angina, which we encounter mostly in our clinics. Those patients do not benefit from revascularization, and conservative management is sufficient. Again, this is something we do not practice or adopt in our calculators. I think this should be almost like the CHADS score when you come to see us whether we should pursue of invasive strategy or continue with medical therapy.

Wael Jaber, MD:

Now, we go finally to the CLARIFY registry. Venu mentioned it earlier, and this is actually a very nice registry I was acquainted with about a year ago when it came out. And this involved 45 countries and they followed these patients yearly for five years. And the way they followed them is where these are patients with established CAD, about one fifth of them had stable angina at baseline, and they followed them for five years every year with a Seattle Angina Questionnaire, and they did not interfere with the medical therapy. Then, they found that 40 percent of patients had no angina in one year, so 22 percent had angina at baseline, 40 percent of those will have no angina at one year. And you can see here that patients with angina had resolved that one year with conservative management were not a high risk of cardiovascular death than those who experienced angina initially.

Wael Jaber, MD:

Now, here's the complex slide. These are patients with angina for one year. You can see here, if you follow them for one year here, this is baseline angina. At one year, a lot of those patients will not have angina and that angina dwindles down as the time goes by to five years. And you can see here, most of these patients did not receive revascularization. So, this is not due to a revascularization effect, this is due to effective anti-anginal management. And in patients who have not been at one year at baseline, very few go on to develop angina down the road. Again, this is a very important baseline check for the patients to figure out where they are and how they will progress. Now here, which patients will have events? Now, there is a relationship between the presence of angina subjectively by the patients and actually how they will do over time. And you can see here, patients who have angina that's persistent over time will have actually more event rates than patients who have no angina, whether they started with angina or they started with no angina. So, the development of angina or the persistence of angina over time is associated with higher event rates. So, we should listen to the patients from that standpoint. However, if you look at the end of the follow-up, the event rate 3.9 percent had anginal symptoms at the end of follow-up period, which is five years, 7.2 percent had died. Event rate 1.4 percent per year. This is in 45 different countries, so this is not at the Cleveland Clinic, this is everywhere. And 3.9 had undergone revascularization, so only 3.9, very few patients, at the rate of less than 1 percent per year, and 3.3 percent had either had an MI or urgent revascularization at the rate of 0.6 percent per year. Again, very low event rate for death, revascularization, and MI.

Wael Jaber, MD:

Finally, I think this is the slide that I like most because now we have two targets. We have angina relief target and event prevention target. Venu talked about that as aspirational going forward and the angina relief target. I think most of us give up very early on this angina relief target, including myself. And we just say, okay, you have angina, you have positive stress test, let's move on and do something about it. I think we should use standard definition for stable CAD and hopefully this will become part of our medical records. We should use the Seattle Angina Questionnaire yearly, not only as a quality-of-life measure, but also as a prognostic measure and as a tool to address changing therapeutic strategies for these patients going down, down the road. And we have to reassess the value of revascularization where we have no data, especially impaired LVEF and especially in the era of ARNIs and newer diabetic medications as new optimum medical therapy. And finally, we should celebrate and own the low event rates. This is something we achieved over the past 20, 30 years. We do not celebrate and own it enough. Guideline-directed medical therapy, optimum medical therapy works very well, and the event rate is very low. Thank you.

Faisal Bakaeen, MD:

I'm going to start by saying why CABG? Well, if you look at the culprit lesions for acute MI, they occur in the first seven centimeters of coronary. When you do a bypass, you go beyond that, you go to mid to distal vessel. And if you use a mammary and you leave the OR with a patent mammary, that mammary should stay open forever. So, there's a prophylactic role, I think, for CABG. And when we talk about stable corona artery disease event rate is low, but we're not looking at one year, we're not looking at five years, we're looking at 30 years. This is an 88-year-old male who had a CABG for stable corona artery diseases 30 years ago, and his native circulation is totally down. No medicine can open those maybe stents they can try, but this patient is living because of a 30-year-old LIMA that supplies the entire heart through collaterals.

Faisal Bakaeen, MD:

So, when do we do CABG? Well, we'll look at the guidelines to guide us. And this is the 2018 European guidelines. And those guidelines say that if you have left main disease or multi-vessel disease including proximal LAD, then that's a class one indication for CABG regardless of the ejection fraction. The North American guidelines also said the same through different iteration over the years until 2021 when that was changed. They stratified patients depending on their EF. If the EF is depressed, severely depressed, less than 35 percent, then CABG remains a class one. But then if the EF is mild to moderate, it was downgraded to 2A, and if it is at normal EF, then it becomes a 2B. The endpoint is survival here. It's not angina, it's not MACE survival. And we're looking at a downgrade based on the EF. If we look at the evidence that was supplied in the tables, nothing in it shows that CABG for a normal EF multi-vessel disease is less than a class one because the first reference that was cited, and there were four references cited for the downgrade to 2B is the LIMA use of meta-analysis. And regardless of the EF, in that LIMA use of meta-analysis, there was a survival advantage to CABG.

Faisal Bakaeen, MD:

The second out of the four references were the European study which showed survival advantage in three-vessel disease and two-vessel disease with proximal LAD. And most patients had actually normal EF. But those references, two out of the four, were labeled as old as if there was an expiry date. So, let's look at the new evidence. And we all agree medical management has improved. Let's look at the new evidence. ISCHEMIA trial is an excellent trial, but the way it was designed, it was comparing Initial, and I want to capitalize I initial, Initial conservative strategy, non-invasive strategy versus invasive strategy. So, not a single patient was actually randomized to CABG, and not a single patient was actually randomized to PCI. It's important to understand that. And only 26 percent of patients who underwent invasive intervention were CABG. The vast majority were PCI. In fact, in the invasive arms, more patients received medical therapy than CABG and less than 50 percent of patients had a proximal LAD lesion. I can't remember the last time I did a CABG on a patient with less than 50 percent LAD lesion. We're talking about two different populations here. The CABG population is at the end of the spectrum. Everything else is here. And if we talk about time lead bias, or lead time bias, then maybe medical management and conservative management is fantastic in that early phase. But as you move with heavy atherosclerotic burden, complex coronary artery disease, we're talking about different animals that ISCHEMIA perhaps did not address to the extent that it needed to. But that wasn't the intention of ISCHEMIA. Let's be clear about that.

Faisal Bakaeen, MD:

Now, the median follow-up was 3.2 years. Again, the cath that I showed you was 30 years, and there was 21 percent crossover. So yes, initial medical management is excellent, but keep your eyes open because many of those patients will actually cross over to intervention. The second... oh, fourth reference actually, or the second new reference was a meta-analysis that ISCHEMIA was the largest part of in terms of the size of patients enrolled. And most patients in this meta-analysis, 84 percent were PCIs. In fact, half of the randomized trials did not have a CABG arm. And the main follow-up was 4.8 years. Again, short follow-up.

Faisal Bakaeen, MD:

Again, this is in my opinion, inadmissible evidence when it comes to the CABG cohort. You can't use that as evidence to say that CABG is no longer a beneficial therapy in patients with complex coronary artery disease because you only looked at a simpler format, an earlier format, of coronary artery disease. You looked at very short follow-up and you closely followed those patients and flipped them over to intervention when it was clinically necessary. So, I think the evidence is clear. I think medical therapy is fantastic and it should be reasonable to use medical therapy as an initial first-line therapy in patients with low to moderate atherosclerotic burden, and then closely follow them up and refer them to intervention when needed. And I think the evidence, no surgeon is going to argue against that.

Faisal Bakaeen, MD:

But these are the guidelines. I mean, we respect them. They're excellent for the population level, the average patient, but when it comes to tailoring therapy for a specific patient here at the Clinic, we have a heart team. Me and Jay, Mike Lincoff, Krishnaswamy, Venu Menon. I mean, we have ad hoc heart team meetings every day on the phone, text messaging back and forth. And we decide this patient gets medical therapy, this patient gets PCI, this patient gets CABG. And that case that was presented earlier was my patient, Amit showed you. I was going to do bilateral mammary. I thought that the RITA would stretch in situ to the proximal PDA. And he's a younger guy. But then Jay said, you know what? That LAD doesn't look critical to me. Let's see what we can do about it. And we made the right decision, I believe, for that specific patient.

Faisal Bakaeen, MD:

How do we do CABG? I'm not going to spend much time about on versus off pump because the default approach is on pump, and there are many studies that support that, but there are select patients, select scenarios where off pump is useful, and we use it in about 15 percent to 20 percent of our patients at the clinic.

What about multi-arterial grafting? In North America, about 85 percent of patients get a single mammary in all veins. Very few get radial or beta grafting and that has been flat over the years. Well, partly because the surgeons look at the evidence and they're not convinced. That was a study that we presented recently. The largest randomized trial to date comparing radial artery to saphenous vein conducted at 14 VA centers with a hundred percent follow-up at 17.7 years length of follow-up showed absolutely no difference in survival.

Faisal Bakaeen, MD:

The curves, as you can see, overlap all along between patients who receive a saphenous vein versus radial artery to the second most important target. And the target was chosen to be at least 70 percent stenotic. Now, this is all-cause mortality. We couldn't look at MACE because the data was not robust, and we couldn't look at patency. So, even though this study shows that there's no survival advantage for using radial instead of saphenous vein, it could not rule out other endpoints such as MACE angina quality of life. Nevertheless, when we looked at the patency data for that VA study, although incomplete numerically, there was no difference between the radial patency rate and the saphenous vein patency rate. What about using bilateral mammary? Let's look at the randomized evidence. This is the ART study by Dr. Taggart. Again, at 10 years showing absolutely no difference in MACE or all-cause mortality. More surgeons said, well, why should you use bilateral mammaries? Well, but there were caveats about this study. There was 14 percent crossover from beta to CTA, reflecting surgeon inexperience and low level of comfort in using bilateral mammaries. And about 22 percent of the CTA arm, which is a single internal thoracic artery, actually crossed over but received the radial artery. So, that may have diluted the effect because you incorporated radials into the CTA arm. And target the lead investigator of the CTA study indicated that in the hands of surgeons that enrolled 50 plus patients, there in the intention to treat analysis a significant divergence of the curves in favor of beta.

Faisal Bakaeen, MD:

So, is it surgeon experience? Well, before we move on to look at our data at the Clinic, if we look at the as-treated analysis of the ART, those were received multi-arterial grafting meaning two ITAs or an ITA plus a radial. There was a difference in MACE and survival over time. So, the as-treated analysis was positive, the intention to treat was negative. It's hypothesis generating. And if we go back to the experience question, this is Dr. Lytle's study that shows at the Cleveland Clinic with the surgeon’s skill and judgment and patient selection. You can see that there's a difference in survival that kicks in at about eight years in favor of the beta cohort and the beta cohort over time continues to do better in terms of overall survival. We took that step further and correlated the survival advantage when the amount of myocardium or the mass of myocardium supplied by ITAs was increased by sequentialization and adding more bypasses using a second ITA. But we also specified that if you put a second ITA on the non-important vessel, a small diag, a small PDA, you're not going to make a survival difference. To get a survival difference, you get a bypassing vessel that reaches more than 75 percent towards the apex of the heart. In this patient, the caths will show you, not only would they benefit from a LITA to LAD, but they would benefit from a second mammary or second arterial graft sequential to those two important lateral wall vessels.

Faisal Bakaeen, MD:

So, that concept entered into our day-to-day practice. How do we configure our ITAs? Well, we want to avoid competitive flow and achieve a balanced flow. But the patents rate does not get affected by how we use them. We use them in a way to enhance and reach all important target vessels. The volume of CABG at the clinic is amongst the highest in the nation. The outcomes have been consistently excellent with less than 1 percent mortality over the years. Three-star ratings. And our default strategy is multi-arterial grafting. But we have lots of sick and complex patients, not all of them get it. And when there's just an isolated LAD, we do an off-pump MIDCAB or use it with a hybrid approach if the other vessels that need to be addressed are unimportant.

Faisal Bakaeen, MD:

So, in conclusion, CABG remains the standard of care in complex corona artery disease, advanced coronary artery disease. MAG is a boutique practice. Multi-arterial grafting should be used in select patients, by select surgeons, and the surgeon experience impact outcomes. Thank you very much.

Announcer:

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