Aortic valve replacement benefit uncertain in asymptomatic disease with myocardial fibrosis
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Key takeaways:
- Patients with asymptomatic severe aortic stenosis and myocardial fibrosis did not have better clinical outcomes with TAVR vs. surgery.
- However, AVR improved HF symptoms compared with conservative management.
WASHINGTON — Among patients with asymptomatic severe aortic stenosis and myocardial fibrosis, transcatheter or surgical aortic valve replacement did not improve outcomes compared with guideline-directed conservative management.
For the EVOLVED trial, presented at TCT 2024 and simultaneously published in JAMA, Marc R. Dweck, MD, PhD, chair of clinical cardiology, British Heart Foundation Senior Clinical Research Fellow and a consultant cardiologist at the University of Edinburgh, Scotland, United Kingdom, and colleagues randomly assigned 224 patients with asymptomatic severe aortic stenosis and left ventricular myocardial fibrosis (mean age, 73 years; 28% women; mean aortic valve peak velocity, 4.3 m/s) to undergo early intervention with TAVR or surgical AVR or guideline-directed conservative management. The planned sample size was 356 patients, but the trial was stopped due to difficulties with enrollment, partially due to the COVID-19 pandemic, Dweck said at a press conference.
“Perhaps the biggest question in aortic stenosis of the last 60 years is when should we replace the valve,” Dweck said at the press conference. “For many decades, guidelines have recommended that we should replace it in patients with severe aortic stenosis, but only in those who have symptoms due to valve disease. “However, trying to assess symptoms in elderly patients with multiple comorbidities is challenging, and many patients are left with a high risk for death or heart failure. The question, therefore, is whether we should intervene earlier in patients with aortic stenosis.”
At a median follow-up of 42 months, the primary endpoint of all-cause death or unplanned aortic stenosis-related hospitalization occurred in 18% of the early intervention group compared with 23% of the routine care group (HR = 0.79; 95% CI, 0.44-1.43; P = .44; between-group difference, 4.82%, 95% CI, 15.31% to 5.66%), Dweck said during the press conference.
Unplanned aortic stenosis hospitalization occurred less frequently in the early intervention group than in the routine care group (6% vs. 17%; HR = 0.37; 95% CI, 0.16-0.88), but there were no differences between the groups in all-cause death (early intervention, 14%; routine care, 13%; HR = 1.22; 95% CI, 0.59-2.51), he said.
However, compared with the routine care group, the early intervention group was less likely to have NYHA class II to IV HF symptoms at 1 year (19.7% vs. 37.9%; OR = 0.37; 95% CI, 0.2-0.7), according to the researchers.
“In patients who underwent early intervention, the symptoms did not change at 12 months, but in the patients who were in the routine care group, the symptoms deteriorated, with worsening NYHA status, at 12 months,” Dweck said during the press conference.
One factor potentially affecting the results is that, due to the way procedures are scheduled in many European countries, patients assigned early intervention did not get their procedure until an average of 5 months after randomization, Dweck said. He noted the time to intervention in the routine care group averaged 20 months. In contrast, in the EARLY TAVR study of a slightly different population with asymptomatic severe aortic stenosis, primarily based in the U.S., the mean time between randomization and procedure was 14 days, Philippe Généreux, MD, co-director of the Structural Heart Program at Morristown Medical Center, Atlantic Health System, who presented the EARLY TAVR results at TCT, said during the press conference.
The question of when to intervene “will be a fairly nuanced conversation with the patient,” Dweck said at the press conference. “Patients tend to fall into two categories: elderly patients who are feeling well and don’t want to have an intervention ... and other patients who want to be more proactive; they are healthy and well and they want to stay healthy and well, and they are happy to undergo a procedure earlier to maintain their health status. I think it will be a personalized decision for patients to make with their physicians.”
In a related editorial published in JAMA, Robert O. Bonow, MD, MS, the Max and Lilly Goldberg Distinguished Professor of Cardiology and professor of medicine (cardiology) at Northwestern University Feinberg School of Medicine, past president of the American Heart Association and editor-in-chief of JAMA Cardiology, wrote that it is notable that 75% of patients in the early intervention group underwent surgical AVR because TAVR was not yet approved for patients at low surgical risk in the U.S. and Europe at the time of the trial.
“It is possible that the primary event rates in EVOLVED were destined to be similar between early AVR and conservative management because both groups had late gadolinium enhancement evidence of irreversible fibrosis,” he wrote. “Future trials might study whether it is more advantageous to intervene in asymptomatic patients before the development of late gadolinium enhancement.”
References:
- Bonow RO. JAMA. 2024;doi:10.1001/jama.2024.22853.
- Loganath K, et al. JAMA. 2024;doi:10.1001/jama.2024.22730.
Perspective
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Poonam Velagapudi, MD, FACC
This study showed that patients with asymptomatic severe aortic stenosis who were in the early stages of problems as evidenced by myocardial fibrosis on MRI did not benefit from an early interventional therapy.
In contrast to EARLY TAVR, which was a positive trial in patients with asymptomatic severe aortic stenosis, not all the patients in this trial got TAVR. Only about 25% of the early intervention group did, and the rest got surgical AVR. And there was a long wait, averaging 5 months, before patients in the early intervention group got their procedure; 86% got their procedure within the first year after randomization.
Though there was no difference in the primary endpoint, there was a difference in heart failure hospitalizations and aortic stenosis-related hospitalizations, which were lower in the early intervention group. I would think that if somebody has a problem with aortic stenosis in their left ventricle and you treat them, they should probably have an improvement in their quality of life.
It’s not normal practice to get an MRI, and it’s not easy to get an MRI — you need to be in a big center with appropriate staffing. Given the results of this trial and EARLY TAVR, if patients are clearly asymptomatic and have signs of severe aortic stenosis, you need to give them as stress test, as was done in EARLY TAVR, but was not mandated in this trial. You should follow that protocol, and if you determine they have a problem, then they should get an intervention as soon as possible; do not wait for 5 months or 1 year. Six patients in this trial died while waiting for their intervention; if it had been done more promptly, maybe they would have survived.
Also of note, in EVOLVED, the bad outcomes in the early intervention group all happened in the first year, whereas they were more spread out in the conservative group. I think that is because surgery itself is more invasive and may be linked with more early problems than TAVR. A trial with a larger number of patients that looks only at TAVR in this population might have better outcomes.
Only 28% of patients in this trial were women, the confidence intervals were wide and it must have been difficult to do MRIs during the height of the COVID-19 pandemic. So the results have to be taken with a grain of salt, and another trial is needed.
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Dweck MR, et al. Late-breaking clinical trials: Session I, in collaboration with The New England Journal of Medicine. Presented at: TCT Scientific Symposium; Oct. 27-30, 2024; Washington, D.C. (hybrid meeting).
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