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Some people with severe aortic stenosis may be at higher risk for events if they wait to get an aortic valve replacement -- even if their left ventricular ejection fraction (LVEF) measures are in the normal range, a registry study suggested.

Among those whose aortic stenosis was managed conservatively, according to the Japanese CURRENT AS registry, combined aortic valve-related deaths and heart failure hospitalizations were more common in patients with lower LVEF (72.3% for LVEF <50%, 58.4% for LVEF 50-59%, 38.7% for LVEF 60-69%, and 35.0% for LVEF ≥70%, P<0.001). On adjustment, the groups associated with worse outcomes were LVEF <50% (HR 1.82, 95% CI 1.44-2.28) and LVEF 50-59% (HR 1.77, 95% CI 1.42-2.20) in comparison with LVEF ≥70%.

Patients who did get initial valve replacement had rates of the combined endpoint still favoring higher LVEF, perhaps not with such marked difference (20.2%, 20.3%, 17.7%, 12.3%, P=0.03). Taking into account several confounders, there was no longer any difference among the four groups, according to Takeshi Kimura, MD, of Kyoto University Graduate School of Medicine in Japan, and colleagues.

"Our study demonstrates that survival in severe aortic stenosis is impaired when LVEF is <60%, and these findings have implications for decision-making with regards to timing of surgical intervention," they wrote in .

In an accompanying editorial, James McCabe, MD, of University of Washington Medical Center in Seattle, took it one step further and suggested that "perhaps the floor for 'normal' LVEF in the setting of aortic stenosis has been set too low."

"Current American guidelines recommend aortic valve replacement for patients who have severe, high-gradient aortic stenosis and either: symptoms attributable to aortic stenosis or left ventricular dysfunction, defined as an LVEF < 50%."

The question is whether that second requirement is really necessary for patients with hemodynamically severe aortic stenosis to get upfront aortic valve replacement. "In light of these provocative observational data and radical secular changes in the treatment [of] aortic stenosis over the last decade, the space is ripe for more definitive data," McCabe said, citing the ongoing , which is a study randomizing asymptomatic patients with severe aortic stenosis, an LVEF >50% and a negative exercise stress test to early transcatheter aortic valve replacement or conservative management.

The CURRENT AS registry enrolled 3,815 consecutive patients in Japan with severe aortic stenosis, 21 of whom were excluded from the analysis for having insufficient LVEF measurements.

Index echocardiography divided the cohort into four LVEF groups with no core lab adjudication, Kimura's group acknowledged. Additionally, LVEF was acquired by the Teichholz method -- not currently recommended in the guidelines -- and not remeasured over time.

McCabe pointed out how few patients underwent prompt surgical aortic valve replacement in this study.

"A total of 1,090 patients (29% of the registry population) had symptomatic, severe aortic stenosis at the time of enrollment (a Class I indication for valve replacement) but were conservatively managed originally, and ultimately only 46% of the total registry population ever received aortic valve replacement over a median of ~3.5 years of follow up," according to the editorialist, who suggested that significant unmeasured risks existed within this specific population, ultimately limiting the generalizability of the present data.