‘Compelling’ TAVR trials spark changes in valvular heart disease guideline
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Amid positive results from large clinical trials confirming the benefits of transcatheter aortic valve replacement, along with expanded indications from the FDA, recently updated recommendations represent the already widespread acceptance of less invasive interventions for aortic stenosis.
The 2020 valvular heart disease guideline from the American College of Cardiology and the American Heart Association also highlight a change in language as well.
“As a clarification, we refer to the procedure as transcatheter aortic valve implantation, or TAVI, now because it involves implantation, not replacement, and the old valve is still there around the new valve,” Catherine Otto, MD, FACC, FAHA, J. Ward Kennedy-Hamilton Endowed Chair in Cardiology and professor of medicine at the University of Washington School of Medicine in Seattle, said.
In an interview with Healio, Otto discussed updated recommendations regarding diagnosis and treatment of aortic stenosis, including the choice between TAVI and surgical aortic valve replacement; at what point in the disease course that intervention is required; current gaps in knowledge; and more.
Healio: With respect to aortic stenosis, what prompted the ACC and AHA to update the guideline?
Otto: Focusing on aortic stenosis, the update is prompted by the rather large number of new randomized clinical trials looking at TAVI, including new data with devices that were available during drafting of the previous guidelines but now have more expanded indications, as well as other aspects of aortic stenosis.
Healio: What were the major updates for diagnosis of aortic stenosis?
Otto: The key element of diagnosis continues to be echocardiography. In this iteration of the guideline, though, we also emphasize the three stages of severe symptomatic aortic stenosis. The first stage includes patients with a high-gradient aortic stenosis who may or may not have a valve area less than 1 cm2 but do have a velocity greater than 4 m/second. The second includes patients with a low left ventricular ejection fraction who have severe aortic stenosis with a small valve area but a lower gradient. The third includes patients with a normal ejection fraction but a small stroke volume because they have a small ventricle, so they have a small valve area and severe aortic stenosis with a lower gradient. This last stage, which is particularly important, is becoming increasingly recognized and often affects women, especially older women. But, overall, the emphasis on all three types has been important.
The updated guideline also focuses on going beyond echocardiography, recognizing that we need additional testing in some patients. Therefore, in addition to echocardiography, we include consideration of CT valve calcification quantification, particularly in those older patients with both low-gradient stenosis but normal ejection fraction, to determine if the valve is truly the causative agent in that patient. And we now more often use B-type natriuretic peptide (BNP) levels to evaluate LV decompensation in patients who appear to be asymptomatic but may have early symptoms.
Healio: How do clinicians determine whether intervention is more appropriate than medical therapy?
Otto: There is no medical therapy for symptomatic severe aortic stenosis, but in the asymptomatic patient, medical therapy is very important and we often forget that. In these cases, we need to carefully assess and address CV risk factors, but we also need to treat hypertension and hyperlipidemia and educate patients about the disease course so that they promptly report symptom onset. However, once a patient has aortic stenosis-related symptoms, there is no medical therapy and the only treatment is to remove the mechanical obstruction, either surgically or with a transcatheter valve. The only situation where we might consider medical therapy is a patient in whom we are using palliative care because of patient comorbidities, age and quality-of-life issues and the decision is not to intervene, which is certainly appropriate for some patients.
Healio: Is it ever appropriate to perform TAVI in a patient without symptoms?
Otto: Currently, the guideline only recommends TAVI in symptomatic patients except for asymptomatic patients with a low LVEF. If you look at the flow chart of timing of intervention in the guideline, TAVI is basically an option in patients with class 1 indications. Asymptomatic patients are a class 2a indication, so it is reasonable to perform TAVI but not necessarily recommended, and in these patients, we recommend only surgical AVR at this time.
Healio: For patients who do require intervention, how do you determine whether TAVI is more appropriate than surgery?
Otto: If a patient has an indication for valve replacement, the next questions pertain to valve type and procedure type. When I’m seeing patients, I try to think of this in two steps. First, what type of valve is most appropriate? Should it be a prosthetic valve with which anticoagulation is not necessary or should it be a mechanical valve that requires anticoagulation? The advantage of mechanical valves is durability. They last for decades, whereas biologic valves wear out. And biologic valves paradoxically wear out more quickly in younger patients. Therefore, the guideline is continuing to recommend mechanical valves in patients aged younger than 50 years.
Of course, there will be exceptions in patients who cannot take anticoagulation for various reasons, and we do offer the option with a weak recommendation for a pulmonic autograft or Ross procedure. Now, for patients aged 50 to 65 years, the decision process becomes more of a discussion between the patient, who is informed about the choices, the surgeon and the cardiologist about whether the patient prefers a biologic valve with the risk that they will need another surgery 10 to 20 years down the line vs. a mechanical valve, which is really durable.
Second, after we have decided that a bioprosthetic valve is a reasonable choice for that particular patient, we then start thinking about TAVI vs. surgical AVR. Of course, with the initial information, any patient would want to avoid surgery, which is why it is important for us to inform our patients about that tradeoff. We have decades of information about durability and surgical outcomes. Moreover, in younger patients — although the relative risk is the same — the absolute benefit of transcatheter valves in terms of mortality reduction and stroke risk is much lower. There were also very few patients younger than 65 included in any of the randomized TAVI trials, so we actually have very few data on transcatheter valves in younger patients, particularly in terms of valve durability. The other consideration in younger patient is the risk for permanent pacemaker implantation, which is higher with a transcatheter valve.
Consequently, the guideline continues to recommend surgical AVR as the preferred treatment option for patients aged younger than 65 years. For patients aged older than 80, we recommend transcatheter valves because the absolute benefit in terms of mortality risk reduction and stroke is much higher while valve durability is less of a concern. For patients aged 65 and 80, however, it is a relative decision between the two options, both with class 1 indications. These ages are given as a surrogate for U.S.-based life expectancy and may vary for different countries or different patient populations. So, the patient whose age is in that mid-range but has a long-life expectancy might be more likely to choose a surgical valve, whereas a transcatheter valve might be a better option for patients with a shorter life expectancy, even if they are younger than 65.
Healio: Because TAVI was approved for patients at low surgical risk in 2019, has there been an increase in patients asking for TAVI instead of surgery?
Otto: Yes, we have seen an increase. Most of us, as patients, would prefer to avoid surgery. Risk still enters the equation, and if a person is at high or prohibitive surgical risk, we would probably go straight to TAVI rather than surgery and go with the biologic transcatheter valves. But younger patients need to be informed and understand what the choices are. Yes, a transcatheter vale will mean a shorter length of hospital stay and less pain upfront, but the issues of valve durability and long-term outcomes must be taken into consideration. So, we would resolutely encourage younger patients to consider the surgical option, which is what the guideline recommends for patients younger than 65. Therefore patients need decision aids and information so they can be involved in the discussion in a meaningful way. The ACC does have materials that patients can look at as well as other online sources.
Healio: Does the guideline recommend at what point in the disease state TAVI should be performed?
Otto: The primary driver of the timing of intervention is symptom onset, but there are a few caveats. First, what are the symptoms? We no longer wait for florid HF, syncope or angina. By symptoms, we mean a decrease in exercise capacity or shortness of breath on exertion — essentially, what would have been considered pretty mild symptoms in the past. We now consider any symptom with severe aortic stenosis to be an indication for intervention. Second, the other problem we face is that many patients are older and even if they have symptoms, they do not recognize that they are having limitations. They simply adapt to the decreased exercise capacity, for instance and don’t complain about it, just assuming that it is normal because they are getting older.
That’s why it’s really important to push the patient on how active they are and how active they were previously. If there is any question about the patient’s level of activity, we recommend an exercise test be considered to evaluate their BP response to exercise and their exercise capacity, with either low BP with exercise or limited exercise capacity being a class 2a indication for intervention. Once again, if a patient seems to be asymptomatic, I might assess BNP level and look for LV decompensation.
In terms of the guideline, in the patient with severe aortic stenosis — a velocity over 4 m/second — and who is active, we would still advocate watchful waiting. However, when we get to the patient with very severe aortic stenosis — a velocity of 5 m/second or higher — or the patient who has rapid disease progression, then it is appropriate to go ahead with intervention.
Healio: What are the considerations for patients who require intervention but have historically been excluded from the large TAVI trials, such as those with bicuspid valves?
Otto: Patients with bicuspid valves tend to be younger, so they are under age 65 and surgical AVR would still be recommended. However, TAVI has been performed in a fair number of patients with bicuspid valves and more data are coming out, so this is an evolving area.
In the guideline, we do not make any specific recommendations about the technical aspects and instead refer to anatomy suitable for valve implantation. As the technique evolves, valve technology improves and interventionalists find that this is an appropriate anatomy, then those patients will be eligible for TAVI. Honestly, I also believe that many people with a bicuspid valve were included in those trials because once the valve is heavily calcified, you can’t tell how many leaflets it has.
Healio: Overall, the guideline represents a move toward less invasive interventions, such as TAVI. What was the driving force behind this push?
Otto: The primary reason is the compelling, new randomized clinical trials in patients with severe aortic stenosis at all levels of surgical risk showing that TAVI is at least equivalent and probably superior to surgery, at least in terms of early mortality and patient outcomes. Additionally, from a patient perspective, TAVI results in a shorter hospitalization, less pain and a faster return to normal activities, so there are many advantages.
Overall, we’ve been talking about moving two things at once here. One is moving toward TAVI vs. surgical AVR, and the issue with this is going to be an ongoing transition as technology improves. Of course, we will all move toward nonsurgical given equivalent or better outcomes over time.
The second is a gradual move toward treatment earlier in the disease course. In the previous guidelines, the patients with the most low-flow, low-gradient aortic stenosis were only a class 2a indication. Now, however, all types of severe aortic stenosis are a class 1 indication. We’re moving toward considering earlier intervention in patients with very severe aortic stenosis or rapid disease progression, and there are several ongoing clinical trials of patients with asymptomatic severe aortic stenosis undergoing early intervention, with some early promising trials suggesting that maybe we should be intervening even sooner. Those have not reached the level of evidence to become recommendations at this point, but that will be something that we will be keeping a close eye on in the future.
Healio: Does the guideline address the need for valve-in-valve procedures?
Otto: We do address that in the prosthetic valve section of the guideline. For most patients with a bioprosthetic valve that has restenosed, we would still recommend a repeat surgical intervention. If the patient is high-risk and surgical reintervention is not an option or there are other reasons why it isn’t the best option, a valve-in-valve is recommended as a reasonable approach in those patients. Clearly, it is technically feasible and can be done, but we do not have a lot of long-term data on outcomes in those patients to say that it should replace the conventional approach.
Healio: Regarding the decision to perform TAVI vs. surgical AVR for aortic stenosis, what role does the heart valve team play? What role does patient preference play?
Otto: The heart valve team’s role is to ensure that the patient considered for both surgical and transcatheter approaches and that the cardiologist seeing the patient is discussing what is the best approach for this particular patient with both the interventionalist and the cardiac surgeon. Heart valve teams are kind of undergoing an evolution as to what is the best way to do this. Is it a formalized meeting? Is it a discussion with the patient? If so, what is the best way to have this discussion? This is going to vary from institution to institution, but the basic concept of the heart valve team is that it is not one physician in isolation deciding what the patient needs. It is a decision made by a group of experts who have considered all the options for each patient.
Now, patient preferences are obviously quite critical. It is ideal if the patient has the information, and we can provide the resources for them to understand what their choices are and why we are making a specific recommendation. Notably, patient preference really becomes key in those 65- to 80-year-olds, regarding whether they want a transcatheter or surgical valve, but this is true even in younger patients. We all have patients younger than 65 in whom we recommend a mechanical valve, but the patient says they skydive or downhill ski or rock climb and don’t want to take warfarin, so they are going to get a biologic valve and that’s the decision. Or we have a young woman who wants to get pregnant, so she’s going to get a biologic valve. Essentially, treatment must be individualized and many patients are going to deviate from the guideline. However, it is important to use the guideline as a starting point and understand why a decision may be different in an individual patient.
Healio: While drafting the guideline, what knowledge gaps were identified?
Otto: With respect to aortic stenosis, the first major gap is in medical therapy. We need more research on basic science and clinical trials of medical therapy that prevent aortic stenosis — both disease initiation and disease progression — with the hope that in the future, people will not need valve replacement at all. The second major gap centers around the question of whether we should be intervening earlier in the disease course. How do we identify which patients would benefit from earlier intervention? And then the third relates to the choice of surgical AVR vs. TAVI. What is going to be the long-term durability of transcatheter valves and will TAVI eventually replace surgical AVR in many patients? Basically, need to know more about the durability of valves and then how do we really select patients optimally for one procedure or the other.
Reference:
For more information:
Catherine Otto, MD, FACC, FAHA, can be reached at cmotto@uw.edu.
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