SEAS data question definition of "severe" aortic stenosis when LVEF is normal
February 24, 2011 |
Dallas, TX - A retrospective look at a prospective trial has raised questions about the echocardiographic criteria by which aortic-valve stenoses should classified as "severe," with all the implications for management, including surgery, the term implies [1].
Typically, either a small aortic-valve area (AVA) or a high transvalvular pressure gradient might point to severe stenosis; but what if AVA suggests severe stenosis while the gradient is low, especially in an asymptomatic patient with normal LV systolic function?
Such patients with "low-gradient 'severe' aortic-valve stenosis" aren't all that rare and have a prognosis similar to patients with aortic disease considered only moderate by echo criteria, Dr Nikolaus Jander (Herz-Zentrum Bad Krozingen, Germany) and colleagues observed based on their analysis of patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.
The findings are reassuring, given concerns that such low-pressure gradients may derive from reduced stroke volume and may therefore be a dire prognostic sign, as some reports have suggested, according to the group in their report published online February 14, 2011 in Circulation.
On the contrary, they conclude, low-gradient "severe" aortic stenosis, which they defined per guidelines as AVA <1.0 cm2 with a mean transvalvular gradient <40 mm Hg, "in general does not indicate advanced aortic-valve disease. [The] indication for valve replacement may safely be restricted to those in whom symptoms can clearly be attributed to aortic stenosis."
In an accompanying editorial [2], Dr William A Zoghbi (Methodist DeBakey Heart and Vascular Center, Houston, TX) argues that—consistent with the SEAS analysis and unpublished data from his center—the 1.0-cm2 AVA threshold should be lowered to more realistically reflect prognosis in such low-gradient, normal-LVEF patients.
"An overestimation of aortic-stenosis severity by [the] current AVA cutoff can have significant implications for management and possibly lead to earlier surgery than is optimal in patients with questionable symptoms," he writes.
"We know from the Jander study that if you don't have comorbidities, you're asymptomatic, and have this low-gradient 'severe' aortic stenosis and a normal ejection fraction, then the prognosis is similar to patients with moderate aortic stenosis," Zoghbi commented to heartwire.
The guidelines' 1.0-cm2 AVA cutoff for severe disease, he said, comes from studies that were generally much smaller and less reliable than the current one. Based on the latter's stronger data, the guidelines for low-gradient, normal-LVEF patients with aortic stenosis should be "refined."
It would make greater sense, according to Zoghbi, to tighten the severe-stenosis AVA threshold to 0.8 cm2, which would make AVA criteria consistent with hemodynamic definitions of severe stenosis.
SEAS had randomized >1800 patients with aortic stenosis to receive daily therapy with simvastatin 40 mg/ezetimibe 10 mg (Vytorin, Merck/Schering-Plough Pharmaceuticals) or placebo. As covered by heartwire, the combination drug significantly lowered LDL-cholesterol levels without significantly cutting the rate of major cardiovascular/aortic-valve events, the primary end point. The finding helped dash hopes that LDL-lowering therapy, especially with statins, might attenuate the progression of aortic stenosis. But the trial was at least as noteworthy for a public debate over whether ezetimibe may have increased the risk of cancer, which the FDA eventually concluded was unlikely.
The current analysis looked at the trial's 1525 asymptomatic patients with an LVEF >55% and either low-gradient "severe" or moderate (AVA 1.0-1.5 cm2 and mean gradient 25-40 mm Hg) aortic stenosis at baseline echocardiography.
The patients with low-gradient "severe" aortic stenosis had greater LV mass at baseline, but the two groups were comparable in LV wall thickness. Clinical outcomes over the mean follow-up of nearly four years, especially for the primary end point of aortic-valve events (CV death, aortic-valve replacement, and heart failure due to aortic stenosis) were also comparable.
Baseline echocardiographic and follow-up (mean, 46 months) clinical outcomes, low-gradient "severe" vs moderate stenosis
| Parameter | Low-gradient "severe" stenosisa, n=435 | Moderate stenosisb, n=184 | p |
| LV wall mass at baseline (g) | 182.3 | 211.6 | <0.01 |
| LV wall thickness (relative to size) at baseline (%) | 36.5 | 37.3 | 0.30 |
| Aortic valve eventsc (%) | 48.5 | 44.6 | 0.37 |
| Major CV events (%) | 50.9 | 48.5 | 0.58 |
| CV death (%) | 7.8 | 4.9 | 0.19 |
a. AVA <1.0 cm2 and mean transvalvular pressure gradient <40 mm Hg
b. AVA 1.0-1.5 cm2 and mean transvalvular pressure gradient 25-40 mm Hg
c. Primary end point; includes death from CV causes, aortic-valve replacement, and heart failure due to aortic stenosis
The primary-end-point rates were similar whether the stroke volume index was above or below 35 mL/m2.
The rates of aortic-valve events and major CV events were significantly greater (74.3%, p<0.01, for both end points) in the 35 patients who met both criteria for severe aortic stenosis—that is, mean transvalvular pressure gradient >40 mm Hg and AVA <1.0 cm2—compared with those with low-gradient "severe" stenosis. Rates of CV death were similar.
According to Zoghbi, the findings suggest that asymptomatic, normal-LVEF patients with aortic stenosis, a low transvalvular gradient, and AVA between 0.8 cm2 and 1.0 cm2 can be managed as conservatively as patients with "moderate" disease.
For surgery to be considered, even for normal-LVEF patients with AVA <0.8 cm2, there would generally have to be symptoms, he noted.
"Where it becomes problematic is when they have comorbidities that can bring about symptoms that may be similar to [those caused by] severe aortic stenosis." For example, if the patient has renal dysfunction and dyspnea, "the difficulty would be in teasing out how much [dyspnea] is due to the aortic stenosis."
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