By Michael H. Crawford, MD, Editor
A large, retrospective, observational study of patients with aortic valve gradients in the severe aortic stenosis range but with aortic valve areas in the moderate range has shown that such patients are not uncommon. Their prognosis is similar to patients with high-gradient severe aortic stenosis.
Unger P, Powers A, Le Nezet E, et al. Prevalence and outcomes of patients with discordant high-gradient aortic stenosis. J Am Coll Cardiol 2024;83:1109-1119.
Severe aortic stenosis (AS) is characterized by a peak aortic jet velocity of ≥ 4 m/s, a mean pressure gradient of ≥ 40 mmHg, and an aortic valve (AV) area ≤ 1.0 cm². However, there are instances where one or more of these parameters is discordant. Much has been written about low-flow low-gradient (LG) severe AS, but there is little on high-gradient (HG) severe AS (velocity ≥ 4 m/s and AV area ≤ 1.0 cm²). Thus, Unger et al conducted a retrospective observational study at a tertiary center in Quebec, Canada, of patients with at least moderate AS (AV area ≤ 1.5 cm² and peak velocity ≥ 2.5 m/s or mean gradient ≥ 25 cm²) between 2005 and 2015 who had echocardiographic and clinical data entered into a database.
Excluded were patients with reversible high-flow states, such as severe anemia, hyperthyroidism, or arteriovenous shunts. The 3,547 patients were divided into four groups based on severe AS being defined as a mean gradient ≥ 40 mmHg and AV area ≤ 1.0 cm²: concordant moderate AS, concordant severe AS, discordant HG-AS (mean gradient ≥ 40 mmHg, AV area > 1.0 cm²), and discordant LG-AS (mean gradient < 40 mmHg, AV area ≤ 1.0 cm²).
A subset of 716 patients had an AV calcium score calculated from gated computed tomography (CT) scans and adjusted for sex. The primary endpoint was all-cause mortality. At baseline, discordant HG-AS was found in 163 patients (4.6% of the total population and 11.6% of the patients with HG-AS); 1,131 patients (32%) had discordant LG-AS; 1,010 patients (29%) had concordant moderate AS; and 1,243 patients (35%) had concordant severe AS.
Discordant HG-AS patients at baseline had a larger stroke volume and a greater left ventricular (LV) ejection fraction (EF) compared to the other groups. Also, aortic regurgitation (AR), especially grade 3 or 4, and bicuspid valve were more common in the discordant HG-AS group. In addition, these patients had larger LV outflow tract diameters and higher stroke volume indices. During the median follow-up of eight years, there were 946 deaths and 2,399 AV replacements.
On adjusted multivariate analysis, the mortality rate of discordant HG-AS was similar to that of patients with concordant severe AS (hazard ratio [HR] = 0.98; 95% confidence interval [CI], 0.66-1.44; P = 0.91) and discordant LG-AS (HR = 0.85; 95% CI, 0.58-1.26; P = 0.42), but higher than that of patients with concordant moderate AS (HR = 0.54; 95% CI, 0.036-0.81; P = 0.003). AV calcium score in the discordant HG-AS patients was not significantly different from that of concordant severe AS patients.
After adjustment for AV velocity, the presence of AR did not affect survival significantly. The authors concluded that discordant HG-AS is not uncommon, and a pressure gradient ≥ 40 mmHg indicates a poor prognosis regardless of the calculated AV area and the presence of any AR.
COMMENTARY
As if trying to figure out which patients have true severe AS is not hard enough already, here is another discordant subgroup to worry about. First, we have the Doppler echo technical problems, such as failure to account for elevated outflow tract velocities (hypertrophic cardiomyopathy), pressure recovery issues (very small ascending aortas), and erroneous geometric assumptions (outflow tract is a circle). Then we have the flow gradient mismatches: low-flow low-gradient severe AS as the result of reduced LV EF (valve area < 1.0 cm², pressure gradient 30 mmHg to 40 mmHg), and paradoxical low-flow low-gradient with normal EF but low stroke volume index because of a thick-walled small cavity LV. Now the Unger et al paper presents discordant HG-AS, where the pressure gradient is > 40 mmHg, suggesting severe AS, but the valve area is in the moderate range (> 1.0 cm²).
In their series, this occurs in > 10% of patients with AS and a high AV gradient, but in < 5% of patients with moderate to severe AS. The researchers demonstrate that discordant HG-AS patients have a prognosis and CT AV calcium scores similar to those with severe AS. Also, they often have a bicuspid valve and mixed AV disease with significant AR as well.
The researchers’ data support the concept of pseudo-moderate AS, where the high pressure gradient caused by high flow opens the valve more and if flow were reduced, the valve area would decrease. It has been shown that there is some pliability even in calcified valves. Their data show that the discordant HG-AS patients did have higher stroke volumes than the severe AS group. One theory is that high gradients caused by increased flow could damage the AV and accelerate calcification.
The strengths of this study are its large size, the exclusion of patients with obvious high output states, and the inclusion of patients with AR and mitral valve regurgitation. However, there are weaknesses to be considered. This was a retrospective, single-center study without a core laboratory. CT valve calcium studies were only available in a subgroup. No three-dimensional echocardiographic information was available, so the often-elliptical shape of the LV outflow tract could not be considered, and AV area may have been overestimated in these HG patients.
The clinical message here is that patients with HG-AS but calculated AV areas > 1.0 cm² calculated by Doppler echocardiography should be evaluated carefully for a high outflow state. If found, it should be corrected if possible, but if not, the concept of pseudo-moderate AS should be considered, since such patients have a prognosis similar to patients with severe AS. Also, CT AV calcium scoring may help with this assessment.
