Surgery Beneficial Even in Early-Stage Aortic Stenosis, RECOVERY Hints

Even in asymptomatic patients with aortic stenosis (AS) and minimal signs of cardiac damage, early treatment with surgery provides a long-term survival benefit over conservative management, a new analysis of the RECOVERY trial shows.

Researchers assessing the prognostic value of a disease classification tool—which relies on the degree of damage to stage AS—found much lower rates of CV or all-cause death at 8 years for patients in the lower stages compared with higher stages. But surgery across all disease categories still offered benefits over conservative management, they said.

“Because the risk-benefit ratio of early elective AVR over conservative management in asymptomatic AS may differ according to stages of cardiac damage, further prospective studies will be necessary to facilitate the identification of patients that may benefit from early intervention,” write Sung-Ji Park, MD, PhD (Asan Medical Center, Seoul, Korea), and colleagues in a research letter published today in the Journal of the American College of Cardiology.

Commenting for TCTMD, Philippe Généreux, MD (Morristown Medical Center, NJ), who proposed the cardiac damage staging classification used by the authors, said it provides more evidence that asymptomatic cardiac damage has a real impact on prognosis, calling it a “silent killer.”

“The validation of this concept of staging cardiac damage within a population with very severe AS with no symptoms is extremely important,” he noted. “We still are debating what to do with these patients, and the ongoing EARLY-TAVR trial will give us more information to help with that.”

 Staging as an Important Predictor

For the RECOVERY trial, 145 asymptomatic patients with very severe aortic stenosis (defined as aortic valve area ≤ 0.75 cm² with peak aortic jet velocity ≥ 4.5 m/s or mean transaortic gradient ≥ 50 mm Hg) were randomized to early surgery or conservative management. Over a median follow-up of 6.2 years in the early-surgery group and 6.1 years in the conservative-care arm, cumulative operative mortality or death from cardiovascular causes (the primary endpoint) was lower with early surgery (HR 0.09; 95% CI 0.01-0.67), as was all-cause death (HR 0.33; 95% CI 0.12-0.90).

Park and colleagues categorized the RECOVERY patients into five stages of extravalvular cardiac damage and used a modified staging scheme for asymptomatic AS. At the time of study enrollment, 59% of patients were in stage 1 (LV damage), 34% were in stage 2 (left atrial damage), and 7% were in stage 0 (no damage).

When we find a cancer, you remove the cancer, you don't wait for symptoms or more extensive cancer. Philippe Généreux

Time-to-event curves showed that compared with stage 0-1, CV death was higher in the stage 2 group at 8 years (22.8% vs 9.2%; log rank P = 0.067), as was all-cause death (35.3% vs 13.6%; log rank P = 0.039). After multivariable adjustment, higher staging classification was confirmed as an independent predictor of the primary endpoint (HR 3.94; 95% CI 1.33-11.74) and all-cause mortality (HR 3.74; 95% CI 1.69-8.32).

For patients classified as stage 1, the cumulative incidences of the primary endpoint and all-cause mortality at 8 years were 2.3% and 8.1% for early surgery versus 19.4% and 23.3% for conservative management. Similarly, for patients classified into stage 2, the cumulative incidences of the primary endpoint and all-cause mortality at 8 years were 0 and 18.2% for early surgery versus 37.4% and 46.5% for conservative management.

To TCTMD, Généreux said one thing that differentiates this study from some others is that none of the RECOVERY patients were in stage 3 (pulmonary vasculature damage) or stage 4 (right ventricular damage), which he finds odd, since other series of similar patients suggest that at least some of them will fall into those categories. He added that the finding may reflect a less-than-rigorous echocardiographic evaluation. The RECOVERY investigators say the absence of patients in higher stages was due to the fact that “entirely asymptomatic patients during ordinary physical activity were included, [such that] study patients were relatively younger and had few comorbidities.”

While debate will no doubt continue about when to intervene in patients with no symptoms, and what that intervention should consist of, Généreux said this study and others help elevate the conversation about the dangers of what has been perceived as “minimal” cardiac damage.

“When we find a cancer, you remove the cancer, you don't wait for symptoms or more extensive cancer. With aortic stenosis, I think we've learned to be complacent because the only option in the past was open-heart surgery with all the recovery and the invasiveness of the procedure. Now that we are living in a world of less-invasive procedures where TAVR has become a dominant therapy, it's become much more clear that maybe we should be more aggressive with these patient and intervene earlier before there is extensive cardiac damage,” he said. “We have to talk about the price of waiting. We have to talk about what we consider clinically significant AS. The timing of the intervention should not be based only on how severe the AS is, but also how clinically significant the impact is on the patient.”