This transcript has been edited for clarity.
Michelle O'Donoghue, MD: Hi. This is Dr Michelle O'Donoghue, reporting for Medscape from day 1 of the AHA Scientific Sessions, which this year are being held virtually. Live on the scene I have Dr Pat O'Gara, who really needs no introduction; he's certainly a world leader on the topic of valvular heart disease. Today's late-breaking session tackled two important trials that are also being published simultaneously. Let's get down to it. Welcome, Pat.
Pat O'Gara, MD: Thanks very much, Michelle. Great to be with you.
AVATAR: Asymptomatic AS
O'Donoghue: The first trial we're going to discuss is AVATAR, which studied a patient population that had asymptomatic aortic stenosis (AS). It has been a conundrum as to how to manage the asymptomatic patient who has severe AS and a normal stress test. Would you like to walk through the study design?
O'Gara: Absolutely. First and foremost, it's important to recognize that this was a multinational study that was conducted largely in Eastern European surgical sites comprising countries such as Poland and Serbia. Second, these are patients, as you pointed out, with asymptomatic severe AS, and mean jet velocity across the aortic valve in these patients was 4.5 m/s. They also had normal left ventricular systolic function, and they had low surgical risk.
They were randomized to a strategy of early surgery vs watchful waiting and the development of a class I indication or a class IIa indication for intervention. All of the patients in this study underwent exercise testing at the individual sites in order to verify the absence of a class II indication that might prompt early surgery.
O'Donoghue: What were the top-line results of the AVATAR trial?
O'Gara: The top-line results are directionally similar to those that we understood from the investigators of the RECOVERY trial that was announced 2 years ago, also at the AHA — namely, that early surgery appears to be associated with a reduction in adverse outcomes in a population of low surgical risk patients with asymptomatic severe AS.
In this trial specifically, there was a reduction in the composite endpoint. The composite endpoint was a bit unusual, I think, for a population of patients with severe AS. The endpoint comprised all-cause mortality, myocardial infarction, stroke, and hospitalization for heart failure. As you know, from your own practice and experience, stroke and myocardial infarction are not particularly common in a cohort of patients with isolated severe AS followed over time. There are also concerns about all-cause mortality vs cardiovascular mortality, which I think would be of greater interest to the cardiovascular community.
O'Donoghue: It was quite interesting that all-cause mortality trended in favor of early surgery because I might have thought at first blush that there would be some excess early hazard from going to the OR. They were low-surgical-risk patients. It is interesting to see that, after the first 6 months or so, the curves started to diverge in favor of earlier surgery.
O'Gara: I think so. I think it's also important to point out that there was differential follow-up with respect to the duration of follow-up. The patients in the conservative arm were followed on average for 7 months longer than were the patients in the surgery arm. That may penalize the conservative arm as well. Within those patients treated conservatively, there were at least three patients who died of COVID pneumonia, and that gets back to the question as to whether cardiovascular mortality might be a more appropriate endpoint.
This is a relatively short-term trial with relatively few events; there were fewer than 40 events in total. It would be desirable to have more information about this category of patients to see whether we can extend this type of strategy to patients who are treated with transcatheter technology compared with open surgical valve replacement.
It's important to emphasize that these are surgical trials, not transcatheter trials.
O'Donoghue: That is an important point. One last question before we move on to the next trial. For our asymptomatic patients with severe AS, we're thinking about the OR for patients who either have a low ejection fraction or have abnormal stress test findings. Do you think that we should be changing our practice based on the current findings or is that premature?
Results In Line With RECOVERY
O'Gara: I think that our practice has already changed. Michelle, I think that the Korean investigators who presented the RECOVERY trial 2 years ago showed in a population of patients, who they described as having very severe AS and low surgical risk, that there was a clear benefit to early surgery.
In major surgical centers where there is an adequate experience as well as an adequate infrastructure of support, these low-surgical-risk patients with very severe AS, who are otherwise asymptomatic and do well on exercise testing, are now being preferentially referred for surgery, at least in the younger group for whom surgery might be contemplated.
As you also know, everybody wants a TAVR and we don't have that information right now. I think that the conversation will change over the course of the next couple of years.
Concomitant TR Repair
O'Donoghue: Yes, an important area for exploration. The next trial we wanted to talk about was one that you were involved with. This was in patients who were undergoing surgery for degenerative mitral regurgitation and who had more moderate degrees of tricuspid regurgitation at the same time, and whether or not to address tricuspid valve repair at the same time as their mitral valve surgery.
Do you want to just briefly walk through the study design?
O'Gara: Sure. This is a group of patients who were undergoing surgery for severe degenerative mitral regurgitation, who had either moderate or less than moderate tricuspid regurgitation with annular dilation. This specific cohort was chosen because, number one, there's no equipoise regarding how to treat severe TR at the time of left-sided cardiac surgery. Severe TR should be treated.
In patients with moderate or mild TR, there is wide variability in regard to the surgical approach. Our guidelines have depended to almost an exclusive extent on observational data that stretch back over a course of a few decades and are derived from large, single-center series, where there is a dominant surgeon.
The randomization here was mitral valve surgery alone vs mitral valve surgery plus a tricuspid annuloplasty repair. The composite endpoint was focused on a couple of very important outcomes, namely death, an increase in the severity of tricuspid regurgitation, or hospitalization because of heart failure. The composite endpoint favored the use of tricuspid valve annuloplasty at the time of mitral valve surgery compared with mitral valve surgery alone.
There was a reduction in that composite endpoint, and it was driven exclusively by a reduction in the progression of tricuspid regurgitation to a severe state over a 2-year follow-up. It's interesting to note that in a sensitivity analysis that was not prespecified, patients who went on to develop severe tricuspid regurgitation were largely derived from those who had moderate TR at time of surgery. Only one patient with mild TR with tricuspid annular dilation subsequently went on to develop severe degrees of tricuspid regurgitation over 2 years of follow-up.
The other important observation is that tricuspid valve annuloplasty surgery in this trial was associated with an 11% incidence of the need for permanent pacemaker therapy over the course of the trial. The vast majority of those pacemakers, 80%, were implanted around the time of surgery before patients even left the hospital.
The balance here is the benefit of tricuspid annuloplasty surgery at the time with mitral valve surgery, in reducing the onset of severe TR and all of the consequences of that vs the risk for permanent pacemaker implantation, the need for a device, thrombosis, infection. As you know, tricuspid regurgitation derives from right ventricular pacing. I think that it's important to emphasize that these investigators developed and designed the trial so as to provide 5- and hopefully even 10-year follow-up to see what the net benefit of this intervention might be over a longer timeframe.
Progression of TR vs Pacemaker
O'Donoghue: You hit upon all the key points that I was hoping to raise. One important point of discussion has been how meaningful is progression of tricuspid regurgitation because that was primarily driving the primary composite outcome. As you noted, the duration of follow-up is, on average, 2 years, and we know that severe tricuspid regurgitation certainly has significant morbidity and mortality attached to it.
If there is longer follow-up, it'll be really interesting to see how progression of TR may or may not translate into harder clinical outcomes over time, especially given the striking imbalance in regard to the need for a pacemaker. I was struck that it is in double-digit numbers in terms of the number of people needing a permanent pacer, and that is something that obviously could adversely affect remodeling and have other consequences down the road.
What are your thoughts? Is it premature to incorporate this into clinical practice or should we be more inclined to address the tricuspid valve at the time of mitral valve surgery?
O'Gara: I think that the guideline writing committee will welcome this kind of information. As you know, the guideline development process has changed over the course of the past few years. Putting on my hat as the chair of the AHA/ACC guideline committee, we anticipate making updates to the guidelines at least every 2 years so we don't need to wait for an update in 5 years. By that time, there will be more clinical follow-up from this particular trial.
I'll just end by saying this really is the benefit of doing a randomized controlled trial. I don't think anybody would have anticipated the need for permanent pacemaking, for example, in this population of patients, just like we didn't anticipate the need for a large number of patients who underwent atrial fibrillation ablation surgery, requiring pacemaker therapy.
O'Donoghue: It's such a huge advance to have a couple of randomized trials to help support our clinical decision-making.
Thank you again for this great discussion. I'm sure many people will greatly appreciate it.
Signing off for Medscape, this is Dr Michelle O'Donoghue.
Michelle O'Donoghue is a cardiologist at Brigham and Women's Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she's never strapped on hockey skates.
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Cite this: Michelle L. O'Donoghue, Patrick T. O'Gara. Surgical Consult From AHA: Act Earlier in Aortic Stenosis and Tricuspid Regurgitation? - Medscape - Nov 19, 2021.