medwireNews: More than 10% of patients with high-gradient aortic stenosis (AS) have discordant high-gradient (DHG)-AS, which conveys a poor prognosis irrespective of aortic valve area (AVA) and severity of concomitant aortic regurgitation, according to a study published in the Journal of the American College of Cardiology.
The researchers highlight that DHG-AS is “not an unusual hemodynamic presentation.”
For the study, which took place over 10 years in a tertiary referral center, Philippe Unger (CHU Saint-Pierre, Brussels, Belgium) and colleagues assessed 3547 unselected patients presenting with at least moderate AS, defined as an AVA of no more than 1.5 cm² plus either a peak aortic jet velocity of at least 2.5 m/s or a mean pressure gradient of 25 mmHg or above. The patients had a mean age of 72 years and 63% were men.
In all, 163 (4.6%) patients had DHG-AS, as denoted by a mean pressure gradient of at least 40 mmHg and an AVA greater than 1.0 cm2, corresponding to 11.6% of those with high-gradient AS.
The remaining patients included 28.5% with concordant moderate (CMod)-AS (mean gradient <40 mmHg and AVA >1.0 cm2), 35.0% with concordant severe (CSev)-AS (≥40 mmHg; AVA ≤1.0 cm2), and 31.9% with discordant low-gradient (DLG)-AS (<40 mmHg; AVA ≤1.0 cm2).
Over a median follow-up of 7.64 years, there were 946 deaths and 2399 aortic valve replacements. The primary outcome of overall mortality among patients with DHG-AS was similar to that of patients with CSev-AS and DLG-AS, who had nonsignificant hazard ratios (HRs) of 0.98 and 0.85, respectively, after adjusting for potential confounders including age, sex, comorbidities, and aortic regurgitation severity.
By contrast, patients with CMod-AS were significantly less likely to die than those with DHG-AS, at an HR of 0.54, note the investigators.
The presence of aortic regurgitation of grade 2 or higher had no significant impact on survival in either the whole cohort or in patients with DHG-AS.
The poor outcome in patients with DHG-AS is “likely explained by the high-pressure gradient, which results in increased afterload, the latter being directly related to the extent of cardiac damage, regardless of the AVA,” say Unger et al.
The mean AVA of patients with DHG-AS was 1.20 cm2, similar to that of patients with CMod-AS (1.27 cm2), and significantly higher than that of patients with CSev-AS (0.62 cm2) and DLG-AS (0.74 cm2).
Additionally, mean aortic valve calcification (AVC) scores, measured in a subset of 716 patients using computed tomography, were significantly higher for the 40 patients with DHG-AS than for the 74 patients with CMod-AS and the 281 with DLG-AS (2507 vs 1060 and 1839 AU, respectively), and similar to those for the 321 patients with CSev-AS (2678 AU).
An AVC ratio of at least 1, denoting severe aortic valve calcification and severe AS, was present in 80% of patients with DHG-AS, which was a significantly higher proportion than the 17% of patients with CMod-AS and the 53% of those with DLG-AS, but similar to the 87% of patients with CSev-AS.
The investigators, who state that AVC is “a powerful independent predictor of mortality in patients with AS,” observed that after adjustment, “the presence of severe AVC […] was significantly associated with increased mortality,” in the whole patient cohort, at an HR of 1.49 compared with an AVC ratio below 1.
The patients with DHG-AS had AVA scores consistent with moderate AS, yet high AVS scores synonymous with severe AS, which Unger et al say was “surprising.”
Noting that the stroke volume index was, on average, 1.8 times larger in patients with DHG-AS than those with CSev-AS, they propose that under high flow conditions, the opening of the aortic valve may be increased in patients with DHG-AS, and speculate that “some of these patients might have ‘pseudo-moderate AS,’ a condition in which AVA would be <1.0 cm2 under normal flow conditions.”
In a linked editorial, Crochan O’Sullivan (Bon Secours Hospital, Cork, UK) and David O’Sullivan (Beaumont Hospital, Dublin, UK) highlight the significance of Unger and colleagues’ study, given that it is the largest to date.
They say that “[i]t provides further evidence that physicians should not be reassured by an AVA ≥1.0 cm2 when [transvalvular mean gradients] are high,” adding that “[t]his misinterpretation leads to delayed referral for [aortic valve replacement] and increased patient morbidity and mortality.”
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