Developments in Transcatheter Aortic Valve Replacement

TAVR was first approved by the US Food and Drug Administration (FDA) in 2011 for use in patients with severe aortic stenosis who are ineligible for surgery, and approvals for additional patient groups followed.¹ In 2019, TAVR received FDA approval for use in patients with severe aortic stenosis who are at low risk for death or complications associated with open-heart surgery.²
 
In randomized clinical trials, TAVR was noninferior or superior to SAVR in patients at various levels of surgical risk.³ Ongoing advances in technological design and operator experience have led to continued improvements in TAVR’s safety and complication rates.⁴
 
Sammy Elmariah, MD, MPH, is an associate professor of medicine and chief of Interventional Cardiology at the University of California San Francisco (UCSF), medical director of the UCSF Cardiac Catheterization Laboratory, and codirector of the UCSF Heart Valve Program. Dr Elmariah leads clinical trials evaluating new transcatheter devices for the treatment of heart valve disease, and he is also involved in research exploring ways to expand access to heart valve disease treatments and in studies investigating the potential role of blood biomarkers to guide the timing of heart valve procedures. In this article, Dr Elmariah describes the current state of progress and ongoing developments in TAVR.

With more patients with severe aortic stenosis opting for TAVR, how does the latest generation of transcatheter heart valves improve procedural outcomes and QOL in these patients, especially those considered at high risk or ineligible for traditional surgical intervention?

The TAVR devices have undergone numerous iterations that have made the procedure much safer and much more reliable, and I think the entire community has established more streamlined ways of doing these procedures. Very frequently, efficiency goes hand in hand with safety, so patients are now undergoing this procedure under monitored anesthesia, not general anesthesia. It is being done without intubating patients and without transesophageal echocardiogram guidance, and most patients are going home within 1 hospital day, despite the fact that these are elderly patients with multiple comorbid conditions.
 
Over the years, the devices have become smaller and smaller in profile, which has allowed us to insert these valves using smaller and smaller catheters, so that has certainly made rates of vascular complications lower. Device iterations have also made rates of paravalvular leak — which was initially kind of the Achilles’ heel of TAVR — lower across the board, whether in bicuspid or tricuspid aortic valve disease. Because of the improved safety of this technology and the improved outcomes with the procedure, TAVR has been serially approved for healthier populations and younger patients.
 
Robust QOL improvement is seen with TAVR, and a major advantage of TAVR over SAVR is that patients reap that QOL benefit much more rapidly because they do not have to go through the recovery period and healing process of an open-heart surgery procedure. Generally, with open-heart surgery, the improvement in QOL does not happen until 3 to 6 months after surgery, whereas with TAVR, there is robust improvement in QOL by the patient’s 1-month follow-up visit.⁵

Which patient-level and clinical factors are associated with more favorable outcomes after TAVR, and which patient groups are generally better candidates for SAVR?

I think TAVR works quite well in the majority of patients. The problem that we are having now is that more patients want TAVR than we feel comfortable offering it to, and the biggest variable there is age. We started studying TAVR in the absolute sickest of patients, so in those very early studies, the TAVR outlasted the patients; we never got a good understanding of valve durability in studies done 15 to 20 years ago.
 
In more recent studies, we are studying TAVR in a healthier, younger population of patients over the age of 65. We have a 3- to 4-year follow-up in that patient population, and that was a randomized study (ClinicalTrials.gov identifier: NCT02701283) compared against surgery.⁶ At this moment in time, it seems that valve durability is comparable to surgical valves that are implanted using open-heart surgery. But we do not know what is going to happen down the line, so we are conservatively telling patients that these valves will last about 10 years, whereas with a surgical valve, we tell patients that it will last around 15 years.
 
To be honest, we really do not have great data on either technology, and the current ongoing studies will follow patients for 10 years and will continue to compare the valve performance out to the 10-year follow-up point.⁶ That is really the piece of data that we need to determine whether we can expand TAVR to patients who are younger than 65. Currently, many patients come to us who are in their 50s, or even 40s, and want TAVR; we are forced to say, “It is not approved or appropriate for you, and you need something that is going to last you for 40, 50, or 60 years, not our estimated 10 to 15 years.”

Which advancements in transcatheter heart valve design and delivery systems have contributed to enhanced valve stability and reduced instances of paravalvular leak, ultimately leading to improved patient safety and long-term durability?

The biggest development that has reduced rates of paravalvular leak with TAVR is the addition of a skirt or wrap of some sort around the bottom edge of these prostheses.⁷ Think about a TAVR valve compared with a surgical valve: when a surgeon does a SAVR, they cut out the valve and clean out all the calcium. They essentially have this nice, round, clean annulus in which to sew a brand-new valve. Because they are sewing it in place, they can also make sure that it nicely seals all the way around.
 
However, when we do a TAVR, we go in, open up the valve, and just push the old valve aside, so there are all these nooks and crannies between elements of the valve and the bulky calcium on the valve leaflets where there is potential for a leak of blood around the valve back into the left ventricle. With the addition of these fabric wraps on the bottom of the valve, that softer material can help to fill some of those nooks and crannies, which substantially reduces the amount of paravalvular leak we are seeing.
 
Valve stability has really never been an issue, to my knowledge. These valves are pretty reliable from that perspective. Regarding the future iterations of these valves, what people are starting to think about now is how these valves are going to act when we put more than 1 valve in a patient. Let’s say their first TAVR valve fails 10 to 15 years down the line, and they need a second valve. How is that geometrically going to fit in the patient? Are we still going to re-access the coronaries? Are we still going to have superior hemodynamics for these valves?
 
All of those design elements are starting to be considered now as we think about expanding TAVR to younger and healthier populations. The biggest development that I see in the future is a change in design that maintains access to the coronary arteries, even with repeat procedures. I think that is something that will tremendously help our ability to roll this out to a broader population.

What are some of the more common complications after TAVR, and what strategies do clinicians rely on to help minimize these issues or address them when they arise?

With current-day TAVR, the in-hospital mortality rate is about 1%.⁸ The stroke rate is about 2%.⁹ Major vascular complications have dropped to the single digits as well — about 4% or 5%.¹⁰ So the procedure has become quite safe, which is why it makes sense to expand it to healthier populations. The fact that we are now doing it in low-risk patient populations is dependent on that evolution and improvement in patient safety.
 
It is a bit tough to answer the question of what we do to reduce complications. We are not treating this as a surgical procedure; it is more akin to what is happening in a catheterization laboratory — by removing things such as intubation, transesophageal echocardiogram, placement of an arterial line, and placement of a Foley catheter, we can help reduce complication rates. This is because the more you do to a patient in a healthcare setting, the more opportunities there are for complications. By streamlining these procedures and getting people in and out of the hospital quickly, I think we can reduce some of the complications that were previously attributed to the procedure.

A 2021 paper noted that improvements in TAVR have allowed expansion of the procedure to younger, lower-risk patients with longer life expectancies.³ What are the unique issues and clinical considerations associated with TAVR in this patient population?

When we started doing TAVR, focusing on patients who were very elderly and very sick, it was all about the procedure itself. How do we do the procedure better? How do we do the procedure more safely? How do we perform the procedure more efficiently?
 
Now that we are talking about healthier patients, the added consideration is, how can we provide lifelong management to this patient? If we are seeing a 65-year-old patient and our intent is for that patient to live to 100, then we need to be confident that we can manage that patient’s aortic stenosis for at least 35 years. Technically, on the basis of the current guidelines, TAVR is approved if somebody has a life expectancy of less than 20 years, because the idea is that you can do 1 TAVR that will last around 10 years.¹¹ At that point, you put a second valve in place that will hopefully give the patient another 10 years.
 
Again, I think 10 years is a little conservative, based on the current literature. Hopefully, the valve will last 15 years or maybe even longer, but what we have to think about is what happens when we do a valve-in-valve or a TAV-in-TAV. When you put a valve inside a valve, the second valve pins open the leaflets of the first valve. If the coronary arteries are right behind the open stent frame of a TAVR valve and all of a sudden you pin open the solid-tissue leaflets, you could occlude or obstruct the coronary arteries.
 
That is a major limitation that will become more relevant as we treat younger patients. We have to develop techniques either for removing leaflet tissue or cutting leaflet tissue so that we can ensure there is flow into the coronary arteries when we do a second procedure. Some of the new device iterations are providing larger cells and valve shape differences that may help maintain blood flow into the coronary arteries even with a TAV-in-TAV procedure. Another thing is that when you put a valve in a valve, and maybe another valve in 2 valves, you are going to have a smaller valve each time. Trying to think about what the hemodynamic consequences of that are and how we can mitigate that risk is going to become more important as we move forward.
 
Finally, we need to work in partnership with our surgeons because 1 approach that has been discussed in the literature is whether we could do a TAVR in a younger patient. When that first valve degenerates, maybe we could put a second valve in, and then when that valve degenerates, we would remove it surgically, put in a surgical valve, and then do 2 valve-in-valve TAVRs after that.¹² That would be a whole string of procedures, but the order in which you perform these procedures may allow TAVR to be done at earlier life stages.
 
Our surgical colleagues need to become more proficient in removing these valves, and we may require some device iterations that make it easier to remove these valves surgically because current literature suggests that when these valves need to come out, that can sometimes be a more complex surgery.¹³

An observational study by Elbadawi et al found racial and ethnic disparities in rates of TAVR uptake in the US. While Black and Hispanic individuals constitute roughly 13% and 17.1% of the US population, respectively, these groups represented only 3.9% and 3.7% of TAVR procedures, respectively.¹⁴ What are some of the possible factors driving these disparities?

The disparities are quite stark, and the fundamental reasons are difficult to pin down. It seems that patients who are members of ethnic or racial minority groups frequently are less linked into the healthcare system, and they have less access to specialty care.¹⁵ Either aortic stenosis is identified in a patient and falls through the cracks or a patient is not recognized as having this and not treated until very late in their disease stage.
 
To give you an example and a summary of a recent study we published, we took patients who had already undergone an echocardiogram, so they already had the diagnostic test to diagnose severe aortic stenosis. We looked at the proportion of patients who received a billing code for aortic stenosis, essentially indicating that someone in the healthcare community recognized the aortic stenosis and acknowledged it, added it to the problem list, and was managing it. That very simple step did demonstrate racial and ethnic disparities, with patients of Black and Hispanic backgrounds being much less likely to get the diagnosis code.¹⁵ We looked at the reason, and it seems that people for whom the echocardiogram was done in the inpatient setting were less likely to get the diagnosis code because, of course, providers in the inpatient setting are focused on whatever medical problem the patient is admitted for.
 
If a patient is admitted for kidney trouble or gout or knee pain, for example, and they happen to get an echocardiogram because somebody heard a murmur and aortic stenosis was appropriately identified, once that patient leaves the hospital, who follows up on it if that patient does not have a cardiologist or if their primary care doctor never gets the results of the echocardiogram? Unfortunately, that scenario is more likely to happen in minority groups and people who have a lower socioeconomic background because they do not have as much access to the healthcare system.

What should be the focus of ongoing research in this area to further improve outcomes in patients undergoing TAVR? What are some of the most notable emerging developments in this regard?

The field has done a fantastic job of improving the procedural outcomes, and now we need to shift beyond that and look at how we can improve the delivery of this lifesaving technology to all the patients who need it. We have touched on that issue with the racial and ethnic disparities, but to give you another sense of things, severe symptomatic aortic stenosis that goes untreated results in death in about 50% of patients at 2 years.¹⁵
 
We can treat it with SAVR or TAVR, and those are lifesaving therapies that essentially cure the disease, yet we treat only about one-half of patients in the US who have symptomatic severe aortic stenosis.¹⁶ That means that about one-half of patients likely have a 50% chance of dying within 2 years — that is a tremendous healthcare issue. We can do so much better in caring for our patients with valvular heart disease simply by improving their access to this lifesaving technology.
 
Importantly, these patients need to universally be sent to heart valve teams — teams that are multidisciplinary or that are experts in managing valvular heart disease — so they can determine whether the patient is ready for the therapy and what the appropriate approach is for that patient, whether surgical or transcatheter. A lot of patients are not getting to those specialists, so they do not get the treatment they need. Increasing attention is being given to leveraging technology in the electronic health record — leveraging artificial intelligence or machine learning — to essentially flash a bright light to warn providers that their patients have severe aortic stenosis so the patients can be referred to the appropriate specialists who can manage the disease.
 
This Q&A was edited for clarity and length.

Disclosures

Sammy Elmariah, MD, MPH, reported affiliations with Edwards Lifesciences Corporation and Medtronic.

References

1. Mahmaljy H, Tawney A, Young M. Transcatheter aortic valve replacement. In: StatPearls. StatPearls Publishing; 2023. Accessed August 25, 2023. https://www.ncbi.nlm.nih.gov/books/NBK431075/
 
2. FDA expands indication for several transcatheter heart valves to patients at low risk for death or major complications associated with open-heart surgery. News release. US Food and Drug Administration. August 16, 2019. Accessed August 25, 2023. https://www.fda.gov/news-events/press-announcements/fda-expands-indication-several-transcatheter-heart-valves-patients-low-risk-death-or-major
 
3. Avvedimento M, Tang GHL. Transcatheter aortic valve replacement (TAVR): recent updates. Prog Cardiovasc Dis. 2021;69:73-83. doi:10.1016/j.pcad.2021.11.003
 
4. Rouleau SG, Brady WJ, Koyfman A, Long B. Transcatheter aortic valve replacement complications: a narrative review for emergency clinicians. Am J Emerg Med. 2022;56:77-86. doi:10.1016/j.ajem.2022.03.042
 
5. Lauck SB, Arnold SV, Borregaard B, et al; 3M TAVR Investigators. Very early changes in quality of life after transcatheter aortic valve replacement: results from the 3M TAVR trial. Cardiovasc Revasc Med. 2020;21(12):1573-1578. doi:10.1016/j.carrev.2020.05.044
 
6. Forrest JK, Deeb GM, Yakubov SJ, et al; Low Risk Trial Investigators. 3-year outcomes after transcatheter or surgical aortic valve replacement in low-risk patients with aortic stenosis. J Am Coll Cardiol. 2023;81(17):1663-1674. doi:10.1016/j.jacc.2023.02.017
 
7. Chiarito M, Spirito A, Nicolas J, et al. Evolving devices and material in transcatheter aortic valve replacement: what to use and for whom. J Clin Med. 2022;11(15):4445. doi:10.3390/jcm11154445
 
8. Murthi M, Velagapudi S, Sharma B, et al. Comparison of in-hospital mortality and clinical outcomes between patients aged more than and less than 80 years undergoing transcatheter aortic valve replacement. Cureus. 2022;14(4):e24534. doi:10.7759/cureus.24534
 
9. Huded CP, Tuzcu EM, Krishnaswamy A, et al. Association between transcatheter aortic valve replacement and early postprocedural stroke. JAMA. 2019;321(23):2306-2315. doi:10.1001/jama.2019.7525
 
10. Sardar MR, Goldsweig AM, Abbott JD, et al. Vascular complications associated with transcatheter aortic valve replacement. Vasc Med. 2017;22(3):234-244. doi:10.1177/1358863X17697832
 
11. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;143(5):e35-e71. doi:10.1161/CIR.0000000000000932
 
12. Virgili G, Romano SM, Valenti R, et al. Transcatheter aortic valve implantation in younger patients: a new challenge. Medicina. 2021;57(9):883. doi:10.3390/medicina57090883
 
13. Bapat VN, Zaid S, Fukuhara S, et al; EXPLANT-TAVR Investigators. Surgical explantation after TAVR failure: mid-term outcomes from the EXPLANT-TAVR International Registry. JACC Cardiovasc Interv. 2021;14(18):1978-1991. doi:10.1016/j.jcin.2021.07.015
 
14. Elbadawi A, Naqvi SY, Elgendy IY, et al. Ethnic and gender disparities in the uptake of transcatheter aortic valve replacement in the United States. Cardiol Ther. 2019;8(2):151-155. doi:10.1007/s40119-019-0138-1
 
15. Crousillat DR, Amponsah DK, Camacho A, et al. Racial and ethnic differences in the clinical diagnosis of aortic stenosis. J Am Heart Assoc. 2022;11(24):e025692. doi:10.1161/JAHA.122.025692
 
16. Li SX, Patel NK, Flannery LD, et al. Trends in utilization of aortic valve replacement for severe aortic stenosis. J Am Coll Cardiol. 2022;79(9):864-877. doi:10.1016/j.jacc.2021.11.060
 
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