Outcomes of Patients With Discordant High-Gradient AS

Quick Takes

  • In a single-center retrospective review, discordant high-gradient aortic stenosis (DHG-AS; mean gradient [MG] ≥40 mm Hg and effective orifice area [EOA] >1.0 cm2) was present in 11.6% of patients with MG ≥40 mm Hg undergoing transthoracic echocardiography, and was associated with a higher prevalence of concomitant ≥3+ aortic regurgitation and higher aortic valve calcium score.
  • All-cause mortality for patients with DHG-AS was similar to that of patients with concordant severe AS (MG ≥40 mm Hg and EOA ≤1.0 cm2) and worse than that of patients with discordant low-gradient AS (MG <40 mm Hg and EOA ≤1.0 cm2) or concordant moderate AS (MG <40 mm Hg and EOA >1.0 cm2). After adjustment for aortic velocity, AR had no significant impact on survival.

Study Questions:

What is the prevalence and what are the survival outcomes of patients with discordant high-gradient aortic stenosis (DHG-AS; defined as mean gradient [MG] ≥40 mm Hg and effective orifice area [EOA] >1.0 cm2)?

Methods:

In a single-center retrospective review, 3,547 adult patients were identified who had at least moderate aortic stenosis (AS) (EOA ≤1.5 cm2 and peak jet velocity ≥2.5 m/s or mean gradient ≥25 mm Hg) on transthoracic echocardiography between 2005 and 2015. Baseline clinical and echocardiographic data and aortic valve calcium score (AVC) when available were collected in an institutional database. AS was categorized as concordant moderate (cMod-AS; MG <40 mm Hg and EOA >1.0 cm2), concordant severe (cSev-AS;MG ≥40 mm Hg and EOA ≤1.0 cm2), DHG-AS, and discordant low-gradient (dLG-AS; MG <40 mm Hg and EOA ≤1.0 cm2). AVC ratio was calculated as AVC score divided by sex-specific thresholds (1,200 AU in women; 2,000 AU in men), with AVC ratio ≥1 indicative of severe AS. The primary endpoint was all-cause mortality during follow-up.

Results:

DHG-AS was observed in 163 patients (4.6% of the study population, 11.6% of patients with MG ≥40 mm Hg). ≥3+ aortic regurgitation (AR) was more prevalent among patients with DHG-AS (33 of 163 patients [20.2%]) than in the other three groups (386 of 3,384 patients [11.4%]). During median (IQR) follow-up of 7.6 (7.3-8.0) years, there were 946 deaths, and 2,399 patients underwent aortic valve replacement. After adjustment for potential confounders, survival of patients with DHG-AS was similar to that of patients with cSev-AS (hazard ratio [HR], 1.17; [0.90-1.53]; p = 0.24), and worse than that of patients with DLG-AS (HR, 1.16 [1.03-1.28]; p = 0.02) and cMod-AS (HR, 1.74 [1.34-2.28]; p < 0.0001). After adjustment for aortic velocity, AR had no significant impact on survival. AVC (available in 716 patients, including 40 with DHG-AS) was higher in patients with DHG-AS than in patients with cMod-AS and dLG-AS, and not significantly different from that in cSev-AS. Among patients with DHG-AS, AVC ratio was independently associated with mortality (HR, 2.58 [1.01-6.59]; p = 0.048).

Conclusions:

DHG-AS is not uncommon and associated with survival similar to patients with cSev-AS. The authors conclude that, whereas EOA >1.0 cm2 often is interpreted as moderate AS, a high MG conveys a poor prognosis, regardless of EOA and the severity of concomitant AR.

Perspective:

DLG-AS (EOA ≤1.0 cm2 but MG <40 mm Hg) has been extensively studied, especially in the setting of low-flow low-gradient (LFLG) severe AS. This single-center study found that DHG-AS (MG ≥40 mm Hg and EOA >1.0 cm2) was not uncommon (11.6% of patients with MG ≥40 mm Hg), often associated with concomitant ≥3+ AR, associated with high AVC, and associated with all-cause mortality similar to patients with cSev-AS. As with patients with LFLG severe AS, patients with DHG-AS might represent a heterogenous group, including (for DHG-AS) some patients with EOA >1.0 cm2, owing to overestimation of the left ventricular outflow tract area. However, a mortality of DHG-AS similar to cSev-AS suggests that the after-overload burden of MG ≥40 mm Hg (with or without concomitant AR) is clinically more important than the calculated EOA. Other trials are needed to address how outcomes are affected by intervention in symptomatic and asymptomatic patients with DHG-AS.

Clinical Topics: Noninvasive Imaging, Valvular Heart Disease, Echocardiography/Ultrasound

Keywords: Aortic Valve Stenosis, Echocardiography


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