Podcast transcript
Can you provide an overview of the conditions you and RUSH treat when you employ the use of transcatheter approaches?
At RUSH, we specialize in the treatment of a variety of different structural heart conditions where we use cutting-edge transcatheter approaches. These interventions mainly involve minimally invasive procedures that we perform through catheters, avoiding the need for patients to go for open-heart surgery. Some of the conditions that we treat can be divided into valvular heart disease and congenital heart disease.
Some examples of valvular heart disease that we treat include aortic stenosis, which is a common condition where the aortic valve does not open as it should, restricting blood flow from the heart to the rest of the body. One common procedure that we perform to treat this condition is a transcatheter aortic valve replacement or what we call TAVR, which we perform utilizing advancement of a valve through the femoral artery to replace the older damaged valve.
Another common condition that we treat is mitral regurgitation. This is where the mitral valve fails to close properly and causes the blood to leak backwards into the left atrium. Some of the treatment options that we can provide patients with are catheter edge-to-edge repair or transcatheter mitral valve replacement.
Another common condition is tricuspid regurgitation, which is similar to mitral regurgitation. The blood leaks backwards into the right atrium. This is a very exciting field nowadays within the structural field where there's a lot of new innovations to treat this condition. So this is mainly related to the valvular heart disease.
When it comes to congenital heart disease, these are the birth defects that affect the structure of the heart, and some examples of that include the atrioseptal defects — or what we call patent foramen ovale — and ventricular septal defects. These are congenital heart defects where there are abnormal openings between the different heart chambers. And there are a variety of transcatheter techniques that we can use to close these defects and reducing the risk of complications.
I thought we could go and break these down one by one, starting with TAVR, which is a technology that's been around for about 20 years to treat the aortic valve. Initially, it was met with some skepticism, but now it's moving toward being a mainline therapy. Can you briefly talk about where that technology has evolved to today?
TAVR has indeed come a long way since its inception two decades ago when Dr. Alain Cribier did the first TAVR in France in 2003. As you said, initially it was met with a lot of skepticism. However, TAVR has evolved nowadays into a mainline therapy to treat patients with aortic stenosis, and it has revolutionized the way that we approach aortic valve interventions.
In the early stages, TAVR was really primarily reserved for high-risk patients. These are the patients who cannot go for traditional open-heart surgery. But nowadays, TAVR is being performed routinely on lower risk patients as clinical data have demonstrated the durability and effectiveness of these valves over extended periods of time as compared to surgery.
The design of the transcatheter heart valve has also shown significant improvements that enhance the function and durability of these valves and contribute to better patient outcomes. Also, the procedural techniques, the way that we do these procedures, have become more refined. This allowed smoother and more precise delivery of the transcatheter valve. All of this has led to reduced times where it takes us really about an hour to perform the TAVR procedure, and most of the time we do it with minimal sedation without the need for general anesthesia. This results in better outcomes for our patients, much faster patient recovery as most patients go home the next day.
Who might be an ideal candidate for a TAVR procedure?
The decision for TAVR or surgical aortic valve replacement, what we call SAVR, is typically made by a multidisciplinary heart team. This team mainly consists of cardiologists, cardiac surgeons, and other specialists who come together. We meet regularly on weekly basis to review each patient's data and determine what's the best treatment approach for these patients.
The team looks at variety of factors, including the patient's age, overall health, their anatomy, if there are any coexisting cardiac conditions, and that way we determine the most appropriate treatment approach. The goal is to provide individualized care that would optimize the outcomes for each patient. But in general, the guidelines regarding the decision to go for TAVR or SAVR are primarily driven by the age and the surgical risk of each patient. In general, for younger patients, we prefer surgery over TAVR as patients can have a mechanical valve, which we know is more durable as we expect these younger patients will need multiple interventions over their life course. But on the other hand, this comes at the expense of needing to be on lifelong anticoagulation.
Could you talk about how TAVR is reducing some formerly open procedures to more interventional ones, especially for the older population?
Historically, the only option to treat these patients with aortic stenosis has been open-heart surgery. And there's no doubt that the success of TAVR has led to a significant reduction in the use of SAVR, specifically over the past five years. And this is when several clinical data have emerged that showed that TAVR is as good as surgery, and in some data they even were better than surgery, especially in the lower risk population. This has led to wider adoption of the guidelines to recommend TAVR over SAVR.
Also, the less-invasive nature of TAVR has made it a very attractive option for both physicians and patients. This translated into a much faster recovery and quicker return to normal activities for our patients. It is important to know that TAVR should not be seen as a competitor for SAVR. These two should be complementary. In fact, many of our cardiac surgeons, colleagues and even nationally, are all now trained in doing TAVRs and we routinely do these procedures together, which have improved not only the safety of the procedure but also the outcomes for our patients.
There are a couple of clinical trials I wanted to ask you about that are going on around TAVR. First is the ALLIANCE trial, which is setting the fifth generation of the Edwards valve, and then the PROGRESS trial, which is setting patients with moderate aortic stenosis. Could you talk about the potential impact that these trials will have around transaortic valve replacement?
Yes. First, let me explain what these trials are all about. The ALLIANCE trial is a new study that is studying the safety and efficacy of the newest generation of the Edwards valve. This is the fifth generation, and this valve is called the SAPIEN X4. The main enhancement of this valve is the change in the technology of the valve leaflets. The valve leaflets are treated with a special anti-calcification technology, which is called Resilia. This technology has been studied on the surgical valves previously and it has shown improvement in the leaflets' durability.
This has very important implications. The average lifespan of a bioprosthetic valve is in the range of 10 to 15 years, so improving the technology to last longer will be extremely important, specifically in our younger population. And as we are moving towards our younger population, these valves need to last longer and this is what's hoped for by this Resilia technology.
In addition, the nice feature about the SAPIEN X4 is it also includes a new system which will provide more precise valve-sizing relative to the patient's valve anatomy, and therefore it would also improve the safety and the ease of performing the procedure. On the other hand, the progress trial is looking into something else. It's looking into expanding the TAVR clinical indications. This trial is exploring the role of doing TAVR in patients with moderate aortic stenosis. As you know, we currently only perform TAVR on patients with severe aortic stenosis, and there has been very limited data on patients with moderate aortic stenosis.
So this study is specifically looking to study those who have symptoms and have moderate aortic stenosis. For example, we don't really know what's the best treatment for patients who have moderate aortic stenosis who have poor cardiac function. This trial will help us answer some of these questions and if successful, this can lead to broader indications for TAVR and it would influence changing the clinical practice guidelines and make TAVR more accessible to a larger group of patients.
Are you excited about the direction for both of these trials in terms of the future of the way TAVR is going?
Absolutely, yeah. This will only enhance this technology and the safety and efficacy of doing these procedures in our patients. Definitely progress is going to answer a lot of questions that we don't know much about in the current stage. If not, we just completed enrollment in this trial and we're looking forward to the results of the progress trial over the next couple of years. And we're excited that at RUSH, we've been part of these trials and we've been very active in enrolling patients in these trials.
Let's switch gears and talk about TEER or transcatheter edge-to-edge repair, which has transformed the treatment of primary and secondary mitral regurgitation. Could we first talk about how the recommended guidelines for treating mitral regurgitation has caused the use of TEER to greatly increase over the past decade?
Mitral regurgitation is really the most common valvular heart disease, and it's largely untreated due to the complexity and the high-risk nature of surgery needed to repair or replace the valve. So there's really a large unmet clinical need for a less-invasive treatment approach. TEER is a minimally invasive procedure where we treat the mitral regurgitation by creating a connection between the two leaflets of the mitral valve.
There are currently two TEER systems approved in the U.S. One of them is called MitraClip from Abbott and the other one is Pascal from Edwards. In the beginning, MitraClip was only approved for patients with primary mitral regurg who are at high risk for surgery. These are the patients who primarily have problem with their mitral valve leaflets. Subsequently, with the positive outcomes from the COOPT trial, this has resulted in expanding the clinical indication for patients who would benefit from this technology. The COOPT trial studied patients with heart failure who have secondary or what we call functional micro hemorrhage, and those patients were randomized into receiving the MitraClip therapy on top of optimal medical therapy as compared to just medical therapy, and this has shown significantly better survival and outcomes compared to medical therapy alone. This trial has really resulted in the guidelines to strongly recommend a TEER for this patient population and, in turn, has led to growth in the number of TEER performed.
Could we break down who might be an ideal candidate or an ideal patient for a TEER procedure?
Just as with TAVR, where we discussed that we use a multidisciplinary approach to identify the patients who would benefit from this technology, the same thing applies to MitraClip or TEER. But in general, as I said, we divide patients with mitral regurgitation depending on the methodology of their mitral regurgitation. Is it primary or secondary? Generally, patients qualify for TEER if they have symptomatic mitral regurgitation due to a primary leaflet abnormality, and they are considered to be a high risk for surgery patients with heart failure and who have secondary or functional mitral regurg. These patients qualify for TEER if they fail medical therapy regardless of their surgical risk, and these patients are very closely followed up with by our heart failure colleagues.
Additionally, one important thing to consider is the anatomy of the mitral valve. The anatomy should be suitable for the TEER procedure. Roughly one-third of patients are not considered suitable for TEER due to variety of anatomical reasons such as small valve size, heavy calcification that involves a valve or restricted leaflet movement that makes grasping the leaflet very difficult.
I want to ask you about a clinical trial that RUSH was participating in, which is the APOLLO trial. Could give us a brief overview of that trial.
This is a trial that we're very excited to have here at RUSH. As we just discussed, many patients with mitral regurgitation, about one-third of them do not qualify for TEER for variety of anatomical reasons. So for those patients, TMVR, which stands for transcatheter mitral valve replacement, is a potential option, and this trial is called APOLLO. It is a TMVR trial that where we use the Intrepid valve from Medtronic to replace the mitral valve percutaneously for those who are not good candidates for TEER. This valve is introduced through small incision in the groin. We go through the femoral vein and then we implant a valve inside the mitral valve where it anchors into the leaflets.
Of note, this trial is not only limited to patients with mitral regurgitation. We can also enroll patients with mitral stenosis who have heavy calcification that involves their mitral annulus. This is going to be a groundbreaking trial that, if successful, hopefully will fulfill a huge unmet clinical need for our patients with mitral valve disorder.
One initial finding with the Intrepid valve is that TMVR can eliminate regurgitation entirely in the APOLLO trial. How exactly does that work?
You're absolutely right, and this is a very important finding. About a month or two ago, the one-year early feasibility study of the Intrepid valve was published. It showed that there's a high procedural success rate with low mortality rate and excellent mitral valve function, which basically there was complete elimination of regurgitation at one year.
On the other hand, with TEER, we repair the valve. So we are commonly left with some residual mitral regurgitation. Most of the time it's in the mild-to-moderate range. However, with replacing the valve completely through the Intrepid valve, there's almost complete elimination. It was as high as 98 percent in one year, where the patient had no mitral regurgitation. And this makes sense. With TMVR, the whole valve is replaced where the incidence of residual regurgitation is very low, and this is unlike what we get with the TEER procedure.
How can some of the potential safety concerns for the trial be overcome so that the Intrepid valve could be used as a competitive therapy?
One of the main concerns with the Intrepid valve is a risk of what we call left ventricular outflow tract obstruction. When this valve is implanted across the mitral valve, there is a part of it that overhangs within the ventricle, and this might block the blood flow to the aortic valve, which can be catastrophic. This is why all patients who we evaluate for this trial undergo a rigorous screening process and CT evaluation that includes placing simulated valves in the anatomy to determine if this LV outflow tract obstruction would be an issue. And as a matter of fact, if this is an issue, then these patients will be excluded from the trial.
It's interesting that with the trial that I mentioned with the early feasibility study, the incidence of this catastrophic LV outflow tract obstruction was very low. This was due to the rigorous screening process and very careful CT evaluation to select the appropriate patients for this trial.
We're going to shift gears one last time in our conversation today to TTVR. I'm wondering if we could first talk about the treatments that are currently available for patients with tricuspid regurgitation.
Tricuspid regurgitation is also a very common valve abnormality where the tricuspid valve fails to close properly. This causes blood to leak backwards towards the right atrium, and this problem is very common and is more frequently present in our older and frail patients. Tricuspid valve has always been described as the forgotten valve as there were limited treatment options available apart from open-heart surgery and medical therapy, which mainly involves diuretics.
As I said, these patients are older and frail, and obviously they're not a good fit for surgery because of their age and comorbidities. Currently, there are several transcatheter therapies to repair or replace the valve that are researched. Some examples of these include the TriClip device, Tri-Trick valve, the Evoke and several others. As I said, they're still in the clinical research phase and hopefully within the next year or two, we're going to have some of these options available for our patients.
The TRILUMINATE trial is looking at a promising therapy—the TriClip transcatheter tricuspid valve repair system, which you mentioned for transcatheter repair in patients who have symptoms of heart failure related to severe tricuspid regurgitation. Can you provide a little bit of context or background about the trial?
The TriClip system is a TEER procedure dedicated to the tricuspid valve, similar to the MitraClip or the Mitravalve repair. It is a transcatheter edge-to-edge repair that involves the tricuspid valve. As a matter of fact, we use the same clip that is used in the MitraClip procedure. The main difference between the systems is the way we deliver the clip into the tricuspid valve.
The TRILUMINATE trial is studying the role of this device, the TriClip device, in patients with severe tricuspid regurgitation. Patients were randomized to receive TriClip versus conservative therapy, and just recently the one-year results of this trial were published, which showed an excellent safety profile of this device with reduction in the degree of leakage as well as improvement in the patient's symptoms and quality of life.
Those early results did show that there was an improvement in the patient's quality of life, but there was no improvement between the two groups with heart failure, hospitalization or mortality. What do you think we learned about patients with tricuspid regurgitation with this trial?
Obviously we are still in the very early stages of TTVR, and this study, I think, is a step in the right direction. We definitely have a lot to learn in terms of who are the best patients to benefit from this procedure and how we can improve the outcomes. As you mentioned, there was no benefit in terms of mortality or heart failure hospitalizations. However, the quality of life improved significantly, which is extremely important for our patients who, as I said, frequently do not have better other options.
Additionally, this device has an excellent safety profile with very low adverse events, so the benefit to risk profile of the system is excellent. Obviously, this is still one-year data for the TriClip and hopefully, with longer follow-up and more experience with this device, we will have more conclusive evidence regarding the benefits of this procedure.
What are the next steps in this trial?
Abbott, the manufacturer for the TriClip, has submitted data to the FDA for approval. Given the excellent benefit-to-risk profile of the system, we are expecting approval sometime early next year.
Lastly, I wanted to ask you about the TRIC valve trial. Could you provide a brief overview of that trial and the promise that it holds for patients?
TricValve is another device that is used to treat tricuspid regurgitation. But instead of directly working on the tricuspid valve, the TricValve is implanted in the superior and invader vena cava and therefore prevents blood from going backwards into the systemic veins. This valve, the TRIC valve, can be really a great option, especially in those with difficult tricuspid anatomies, as we don't need to work directly on the tricuspid valve. Many patients with challenging anatomies, for example, if they have a pacemaker lead going through their valve or there's a wide gap between the leaflets, it makes TEER or TMVR very challenging. This is where the advantage of this TricValve come.
The early results from Europe of this device have been very encouraging where they showed that patients who underwent this procedure had significant improvement in their symptoms and the quality of life, and currently this device is being studied in the U.S. through the TricCave trial, of which RUSH will soon be part.
