Melanie Cole, MS (Host): Welcome to AHN Med Talks, an informative resource for physicians across various specialties as we delve into the latest medical insights and best practices, ensuring you stay at the forefront of your field. I'm Melanie Cole, and today our discussion focuses on the AHN TAVR program. Joining me is Dr. Ramzi Khalil. He's an Interventional Cardiologist with the AHN Cardiovascular Institute. Dr.  Khalil , thank you so much for joining us today. I'd like you to start by telling us a little bit about aortic stenosis, what you've been seeing in the trends, the prevalence, the scope of what we're talking about here today.

Ramzi Khalil, MD: Thank you, Melanie. Thank you for hosting me. So aortic valve stenosis is a disease of the aortic valve where the leaflets get restricted and calcified. The most common reason why people have aortic valve stenosis is actually degenerative valvular disease. There's also other entities such as bicuspid aortic valve that degenerate and fails ultimately. Aortic valve stenosis is a fairly common disease of the elderly people. The prevalence of aortic valve stenosis is around 5% in patients above the age of 65, and as you get older, the severity of the disease gets worse and the prevalence gets higher. To give you an idea, so severe aortic stenosis is around 4% of elderly above the age of 70 or 75, and becomes around 10% when they reach the age of 85 to 90. 

The aortic valve stenosis ultimately lead to three entities, can lead to fainting spells or syncope, angina symptoms, or heart failure, and ultimately will lead to death. Once you reach the stage of severe disease, 50% of patients die within two years.

Host: Wow. Thank you for, you know, giving us a really good update on that. Now, how has the landscape of aortic valve replacement evolved in recent years with the emergence of TAVR technology? It's really quite amazing. So tell us about treating high risk aortic stenosis in the critically ill and cardiogenic shock, and speak about how this treatment has really evolved with this kind of technology.

Ramzi Khalil, MD: So the original transcatheter aortic valve replacement was done by Dr. Alain Cribier in France and his colleagues in 2002. It was a rudimentary valve that was crimped on a metal stent and put on a balloon, and actually was done on a very sick patient. The original case was a proof of concept that the actual concept will actually work.

The patient ultimately died from other reasons, but the actual valve did work in the patient. He died from multisystem organ failure and sepsis and pneumonia. Then after that it was felt that we can do clinical trials on patients who have prohibitive for surgery. It means they cannot go for surgery, for surgical aortic valve replacement.

And also it showed that there was a 20% reduction in mortality in these patients compared to patients where were treated, medically or conservatively. Among these patients that were treated conservatively were patients who underwent valvuloplasty of the aortic valve. As we know that actually valvuloplasty of the aortic valve does not work very, very well because the valve will collapse back and recoil as opposed to valvuloplasty of a mitral valve in rheumatic heart disease.

Then ultimately when the cohort of patient in Partner B trial were very like prohibitive, patient for surgery, showed proven mortality benefit at one year, 20% reduction, it means we saved one patient among five patient treated. Then the high risk cohort came out and also showed significant reduction in mortality and was actually similar outcome to surgery.

So this opened the landscape to doing also patient with moderate risk for surgery. Just for the audience to know that what's a high surgical risk versus moderate surgical risk versus low surgical risk. We calculate something called the STS score or predicting mortality at 30 days. If your mortality at 30 days is more than 8%, we call it high surgical risk. Between four and 8% is moderate and less than 3%, usually we call it low surgical risk. More importantly, the data showed ultimately that patient with moderate surgical risk, do as good as surgery, and even maybe better as far as the early recovery, less bleeding, less arrhythmias, and then lower surgical risk patient actually, trial came out, which was the Partner three trial and also the Evolut low surgical risk transcatheter heart valve trial. And it also showed at five years that there's not much of a difference between surgery and actually transcatheter aortic valve replacement in low surgical risk.

We only have data for up to seven years for the low surgical risk. We don't have too much data on the high surgical risk because these patients ultimately died from other reasons because they were very sick and frail. So we could not track them over 10 years. We're waiting for the data for 10 years for the low surgical risk to see whether TAVR in low surgical risk patients actually is non-inferior or similar to actually surgical aortic valve replacement.

So now this is as far as the indications per guidelines. But currently we finished enrolling at Allegheny General Hospital also another entity of patients or a group of patients, which are the asymptomatic patient with severe aortic valve stenosis. This was the early trial, study that was published by Philippe Généreux and his colleagues in the New England Journal of Medicine October, 2024, when it showed that actually, if you even don't have symptoms, so we're not treating patient who have severe aortic stenosis without symptoms and we are actually offering them transcatheter aortic valve replacement to prove they don't have symptoms, we are putting these patients on the treadmill and documenting the lack of symptoms and then this trial came out in October last year, and it showed at a follow up of four years, that the patient who do not have symptoms, but with severe aortic valve stenosis, they do as well as if you observe them. So we can still observe these patients, but around 50% of these patients within one year, even if they don't have symptoms, will end by having symptoms and hospitalized for symptoms of aortic valve stenosis.

And at four years, 90% of these patients ended by having actually transcatheter aortic valve replacement. Not to confuse the audience, there is also further data and trials will be coming out treating patients with symptomatic moderate aortic valve stenosis. So now we're actually treating another subset of patients.

They have symptoms, but they have moderate aortic valve stenosis. And these patients have usually heart failure or atrial fibrillation and dilated ventricles and chambers that we are actually sub selecting. And we're trying to understand whether we can catch the disease even earlier to prevent actually morbidity and mortality.

Host: Wow. Such an exciting time in your field. Speak about the technology of TAVR. Any technical considerations you'd like to share with other providers about the device itself? Robotic assisted. Tell us about the technology.

Ramzi Khalil, MD: Transcatheter water valve replacement went through multiple, multiple, actually evolution. Now we're doing TAVRs on a sixth generation valve. I can always use the example when I talk to my patients. Okay. While you're taking the BMW 1970 and now you're doing like you're putting an X7 BMW. Or you're letting them drive an X7 BMW. So you can see how much technology has evolved with these valves and the most of the technology involved in these valves is actually we put skirts around the valve to prevent leaking around the valve. So we decrease the risk of predor valvular regurgitation. We also optimize the valve stent frame so we can access the coronary arteries, so we can do actually percutaneous interventions through these transcatheter heart valves easier.

And then also we are aligning these valves to the native anatomy. So actually, the Early Trials where we're putting the valves we were not aligning the leaflets of the new valve to the old leaflets. And this will create some issues re-accessing the coronaries and per se, perhaps causing coronary occlusion in the future when we need to do another transcatheter heart valve. So this is number one.

Number two, now when we see patients in our office, let's say I'm seeing a 70 and 75-year-old patient. The problem is not putting the first valve because most of the time these patients are eligible to have a TAVR valve. But the problem is trying to plan what's going to happen for these patients when they're coming in 10 years with failed valve, whether I can do another TAVR in the TAVR. We call it TAV and TAV. So we do CT planning. We look at the anatomy of the aorta of the anulus of the sinuses. There are companies now that they can do 3D reconstruction of the aorta and the valves, and they can simulate what's going to happen with the next valve.

So it's what's going to happen in 10 years if I want to do another TAVR in TAVR to see whether it's feasible or not, because this is very important when we put actually a valve in a patient; these patients are living longer, so we have to plan the future valve in these patients.

Host: Dr. Khalil, when there's so much calcium present in the vessels, which can make existing devices difficult to implant and also valve in valve. What works well in terms of enabling vessel expansion while minimizing vascular injury? Tell us a little bit about pre-planning and what you can do to make this better for the patient and the physician.

Ramzi Khalil, MD: So pre-planning of patients, we pre-plan first the access. So how are we going to put the valve in? So, we get a CAT scan, a whole body CAT scan. It has to be gaited. So we have to do some good measurements of the aortic annulus, where we're going to implant the valve, but also looking at the aortic arch, the aortic iliac access, the femoral arteries.

We need at least a five millimeter vessel size, not heavily calcified to get the valve from the groin, for femoral access. If the access in the femoral arteries is not good enough, we do something called alternative access where we can access and we can implant the valve either from the subclavian artery or from the carotid artery.

We call it transubclavian or transcarotid aortic valve replacement. And then the other thing we look at is the aortic valve calcification, the calcification around the annulus and how much the calcification extends into the ventricle sometimes, because sometimes if you have horrendous calcification, perhaps doing the transcatheter aortic valve replacement is not the right option for the patient.

And this is one of the reasons sometimes we send patient for surgical aortic valve replacement because as you know, the surgeons can excise the calcium and actually implant the valve surgically and suture the valve into the aortic annulus. What we do in the hybrid operating room is number one, we sometimes, if you have severe calcification of the aortic valve, we prepare the valve by doing a valvuloplasty, and then we do the transcatheter aortic valve replacement.

There are two kind of valves there, the self-expanding valve, which actually when we actually release the valve, it because of the body temperature and nitinol is making the frame of the valve will expand to body temperature. These valves, usually they need to be angioplastied even before or after the actual implantation of the valve to ensure adequate expansion.

The balloon expandable valves, usually the balloon that is there and the valve is crimped on it, will help expanding the actual valve when we're deploying the actual valve. Then we assess when we do this procedure for leaking around the valve. If there is substantial leaking, then we might have to put a bigger balloon, or we can add extra volume of contrast in the already existing balloon so we can actually inflate the valve a little bit more gently with some risk. But we have to be very mindful if there is lots of calcium, the these are the risks and the benefit what we want to go very aggressive.

Usually we try to achieve a less than mild aortic regurgitation when we deploy the valve, because anything more than mild can impact future outcome on these procedures.

Host: Dr. Khalil, tell us about the program at AHN and how you collaborate with the multidisciplinary team, including interventional cardiologists, cardiac surgeons, in really doing that pre-planning and determining the optimal approach.

Ramzi Khalil, MD: So originally when they created the clinical trials for transcatheter aortic valve replacement, they called them the Partner trial, and what Partner trial meant is actually the interventional cardiologists were partnering with the surgeons, and this is what we call the multidisciplinary team.

In the multidisciplinary team there is also echocardiographers, imager, radiologist that can interpret and read CTs because you have to understand, when we do the planning, we go full body CT, sometimes we pick up abnormalities like cancers and other reasons, other, abnormalities on the CAT scans.

We have also nurse coordinators. So this is mostly the team. We meet every week on a Monday, usually at AGH. And we go over, perhaps 10 cases. We look at the CAT scans, we look at the actual echocardiograms. We determine the risk of the procedure. We look if the patient is too low risk or very young, maybe they're better served with actually a surgical aortic valve replacement. We look at future planning as a team. What's going to happen on the next valve in 10 years? Are we going to be able to offer these patients another valve procedure or not? And we'll go from there. So essentially, the TAVR team comprises the intervention cardiologist, a surgeon, nurse coordinators, echocardiographer and radiologist.

Host: Wow, that's quite a comprehensive approach. And Dr. Khalil, what is your vision for the program? How will this care model you've described here today improve the way patients receive their care, and for any comorbid conditions that go along with heart failure, valve failure, and the things that go along with heart disease?

Ramzi Khalil, MD: In general, valvar heart disease is actually going to grow. We know that because the population is going to age. And as you get older, all valvular pathologies actually become more significant. Well, it's not only limited to actually aortic stenosis, it's also there with aortic regurgitation, mitral stenosis, mitral regurgitation.

Even now we're doing transcatheter aortic valve regurgitation treatment not stenosis, with our clinical trials. We are also having the TEER team, which is a transcatheter edge to edge repair of the mitral and tricuspid valve in these patients. And we are also doing, transcatheter tricuspid valve replacement and mitral valve replacement. So, the domain of valve heart disease and structural heart disease is growing. As we treat older patients, they are usually sicker patient and they are usually not candidate for surgical interventions. I do anticipate that the burden of valvular disease will be growing, and we have actually data for that. For example, I can use the example of the Olmsted County in Minnesota. I mean, they did a trial in their community and they showed that even though the prevalence of valvular disease may not increase, but the incidence is increasing because of the growing population and the aging of the population.

I do see that there is still a more innovation in structural heart disease, especially in, transcatheter valvular disease. We are now studying entities where we can also do leaflet modification on the transcatheter heart valve. What does it mean is when you have a TAVR valve and then you try to put another TAVR in it, the actual leaflet of the old TAVR might occlude the coronary arteries, so it might take the patient away from that procedure.

Now there are lots of data and lots of trials that are working on actually cutting these leaflets from the original valve percutaneously. So you can put actually a new valve. There are devices on the market and there are very well known procedures actually that have been well published.

I see the future for transcatheter heart valve and other valves, it's going to stay and it's going to grow, but I can also tell you that young patients should be always considered for surgery because it's always easier to have surgical intervention when you're young and it's easier to get a valve in a valve when you get older.

You don't want to operate on an older patient. So what does it mean? And this is a very important concept, what we call TAVR explant. So if you have a failing TAVR valve and you take it out, that carries a very high mortality because these patients are usually older and these patients actually might not do well.

The mortality rate for example, for TAVR explant is around 20 to 30% in one year. So you'd rather give these patients the first surgical option. And then ultimately when that valve will fail in 10 to 15 years, and the patient now is 75 years old, it's very easy to put actually a TAVR valve in a surgical valve.

So these are very important things and physicians should be mindful when they do these procedures to plan the future for the patients that are going to be living in their late eighties essentially, and early nineties.

Host: Dr. Khalil, thank you so much. What a fascinating conversation. You've given us so much to think about. And thank you again for joining us. And to learn more, to refer your patients to Dr. Khalil, please call 844-md-refer or visit ahn.org. Thank you so much for listening to this edition of AHN Med Talks with the Allegheny Health Network.

I'm Melanie Cole. Thanks so much for joining us today.