Better to intervene early with a new valve in patients with severe aortic stenosis (AS) who are asymptomatic, even during exercise, than to wait for the disease to progress and symptoms to emerge before operating, suggests a small, randomized trial that challenges the guidelines.
Of the trial's 157 patients, all with negative results on stress tests and normal left ventricular (LV) function despite severe AS, those assigned to early surgical aortic valve replacement (SAVR), compared to standard watchful waiting, showed a better-than-50% drop in risk for death or major adverse cardiac events (MACE) over 2 to 3 years. The benefit appeared driven by fewer hospitalizations for heart failure (HF) and deaths in the early-surgery group.
The findings "advocate for early surgery once aortic stenosis becomes significant and regardless of symptom status," Marko Banovic, MD, PhD, said during his presentation at the virtual American Heart Association (AHA) Scientific Sessions 2021.
Banovic, from the University of Belgrade Medical School in Serbia, is co-principal investigator on the trial, called AVATAR (Aortic Valve Replacement vs Conservative Treatment in Asymptomatic Severe Aortic Stenosis). He is also lead author on the study's publication in the AHA's flagship journal, Circulation, timed to coincide with his AHA presentation.
"The AVATAR findings provide additional evidence to help clinicians in guiding their decision when seeing a patient with significant aortic stenosis, normal left ventricular function, overall low surgical risk, and without significant comorbidities," Banovic told theheart.org | Medscape Cardiology.
European and North American Guidelines favor watchful waiting for asymptomatic patients with severe aortic stenosis, with surgery upon development of symptoms or LV dysfunction, observed Victoria Delgado, MD, PhD, Leiden University Medical Center, the Netherlands, an invited discussant for the Banovic presentation.
AVATAR does suggest that "early surgery in truly asymptomatic patients with severe aortic stenosis and preserved ejection fraction seems to provide better outcomes as compared to the conservative treatment," she said. "But I think that the long-term follow-up for potential events, such as valve durability or endocarditis, is still needed."
The trial has strengths compared to the recent RECOVERY trial, which also concluded in favor of early SAVR over watchful waiting in patients described as asymptomatic with severe aortic stenosis. Delgado and other observers, however, have pointed out limitations of that trial, including questions about whether the patients were truly asymptomatic—stress testing wasn't routinely performed.
In AVATAR, all patients were negative at stress testing, which required them to reach their estimated maximum heart rate, Banovic noted. As he and his colleagues write, the trial expands on RECOVERY "by providing evidence of the benefit of early surgery in a setting representative of a dilemma in decision making, in truly asymptomatic patients with severe but not critical aortic stenosis and normal LV function."
A Role for TAVR?
Guidelines in general "can be very conservative and lag behind evidence a bit," Patricia A. Pellikka, MD, Mayo Clinic, Rochester, Minnesota, who is not associated with AVATAR, told theheart.org | Medscape Cardiology.
"I think when we see patients clinically, we can advise them that if they don't have symptoms and they do have severe aortic stenosis," she said, "that they're likely going to get symptoms within a reasonably short period of time, according to our retrospective databases, and that doing the intervention early may yield better long-term outcomes."
The results of AVATAR, in which valve replacement consisted only of SAVR, "probably could be extrapolated" to transcatheter aortic valve replacement (TAVR), Pellikka observed. "Certainly, TAVR is the procedure that patients come asking for. It's attractive to avoid a major surgery, and it seems very plausible that TAVR would have yielded similar results if that had been a therapy in this trial."
In practice, patient age and functional status would figure heavily in deciding whether early valve replacement, and which procedure, is appropriate, Banovic told theheart.org | Medscape Cardiology. Importantly, the trial's patients were at low surgical risk and free of major chronic diseases or other important health concerns; their age averaged 67 years.
"Frailty and older age are known risk factors for suboptimal recovery" after SAVR, Banovic said when interviewed. Therefore, frail patients, who were not many in AVATAR, might be "more suitable for TAVR than SAVR, based on the TAVR-vs-SAVR results in symptomatic AS patients," he said.
"One might extrapolate experience from AVATAR trial to TAVR, which may lower the bar for TAVR indications," but that would require more supporting evidence, Banovic said.
AVATAR, conducted at 9 centers in 7 countries in Europe, randomly assigned 157 adults with severe AS by echocardiography and a LV ejection fraction (LVEF) greater than 50% to early SAVR or conservative management. They averaged 67 years in age, and 43% were women.
The trial excluded anyone with dyspnea, syncope, presyncope, angina, or LV dysfunction and anyone with a history of atrial fibrillation or significant cardiac, renal, or lung disease. The cohort's average Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 1.7%.
The 78 patients in the early surgery group "were expected" to have the procedure within 8 weeks of randomization, the published report states; the median time was 55 days. Six of them ultimately did not have the surgery. There was only 1 periprocedural death, for an operative mortality of 1.4%.
The 79 patients assigned to conservative care were later referred for surgery if they developed symptoms, their LVEF dropped below 50%, or they showed a 0.3-m/sec jump in peak aortic jet velocity at follow-up echocardiography. That occurred with 25 patients a median of 400 days after randomization.
The rate of the primary endpoint — death from any cause, acute myocardial infarction (MI), stroke, or unplanned HF hospitalization — was 16.6% in the early surgery group and 32.9% for those managed conservatively over a median of 32 months. The hazard ratio (HR) by intention-to-treat analysis was 0.46 (95% CI, 0.23 - 0.90; P = .02). The HR for death from any cause or HF hospitalization was 0.40 (95% CI, 0.19 - 0.84; P = .013). Any differences in the individual endpoints of death, first HF hospitalizations, thromboembolic complications, or major bleeding were not significant.
If early aortic valve replacement is better for patients like those in AVATAR, some sort of screening for previously unknown severe aortic stenosis may seem attractive for selected populations. "Echocardiography would be the screening test for aortic stenosis, but it's fairly expensive and therefore has never been advocated as a test to screen everyone," Pellikka observed.
"But things are changing," given innovations such as point-of-care ultrasonography and machine learning, she noted. "Artificial intelligence is progressing in its application to echocardiography, and it's conceivable that in the future, there might be some abbreviated or screening type of test. But I don't think we're quite there yet."
Banovic had no conflicts; disclosures for the other authors are in the report. Delgado discloses s peaker fees from Edwards Lifesciences, Abbott Vascular, Medtronic, Merck, Novartis, and GE Healthcare and unrestricted research grants to her institution from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. Pellikka discloses receiving a research grant from Ultromics and having unspecified modest relationships with GE Healthcare, Lantheus, and OxThera.
Circulation. Published online November 13, 2021. Abstract
American Heart Association Scientific Sessions 2021. Presented November 13, 2021. Session LBS.01
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Cite this: Early SAVR Tops Watchful Waiting in Severe, Asymptomatic Aortic Stenosis: AVATAR - Medscape - Nov 13, 2021.