Discordant grading is seen frequently in moderate aortic stenosis (AS) and is associated with increased mortality, according to researchers on a new international registry study, who pushed for better phenotyping of these patients.
The findings were published Monday online in the Journal of the American College of Cardiology ahead of the Aug. 16 issue, with authors led by Jan Stassen, MD, from Leiden University Medical Centre, the Netherlands, and Jessa Hospital, Hasselt, Belgium.
Poor prognostic implications associated with discordant grading – i.., different flow-gradient patterns – in severe AS are already well-established, the researchers noted. However, the prevalence of discordant grading and its implications in moderate AS have remained unknown, they said.
American and European valvular heart disease guidelines define moderate AS by several hemodynamic criteria, including aortic valve area (AVA; 1.0-1.5 cm2), transvalvular mean gradient (MG; 20-40 mm Hg) and peak aortic jet velocity (3.0-4.0 m/s), they added.
“Although the combination of these criteria is easy to use when concordant, patients often present with discordant echocardiographic parameters, having moderate AS based on AVA but less-severe AS based on transvalvular MG/peak aortic jet velocity,” the researchers continued.
“This situation raises uncertainty to the actual severity of AS and may have important prognostic, and potentially even therapeutic, implications.”
The current study, therefore, set out to investigate the prognostic implications of different flow-gradient patterns in 1,974 moderate AS patients (mean age 73 years, 51% men) identified in three academic institutions’ moderate AS registries: Leiden University Medical Centre’s, and those of National University Hospital and National Heart Centre, both in Singapore.
The patients presented with a first echocardiographic diagnosis of moderate AS between October 2001 and December 2019, and followed up for all-cause mortality until March 1, 2021, by reviewing hospital records linked to the governmental death registry database.
All patients underwent complete clinical and echocardiographic evaluation at the time of first diagnosis of moderate AS, and the prospectively collected data were retrospectively analyzed.
Moderate AS was defined as an AVA between 1.0 and 1.5 cm2 and MG <40 mm Hg/peak aortic jet velocity <4 m/s, and concordant moderate AS with moderate gradient was defined as MG ≥20 mm Hg but <40 mm Hg.
Of the cohort, 788 (40%) had discordant moderate AS with low (mild) gradient (MG <20 mm Hg).
The patients with discordant grading were further divided into 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, stroke volume index [SVi] ≥35 mL/m2, and left ventricular ejection fraction [LVEF] ≥50%); “paradoxical” low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL.m2, and LVEF ≥50%); and “classical” low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%).
At baseline, those with discordant moderate AS were significantly older (normal-flow, low-gradient: 75.4 years; paradoxical: 74.9 years; classical: 73.7 years), the researchers noted. They also “had a higher prevalence of arterial hypertension, diabetes mellitus, and previous myocardial infarction; had more impaired renal function; and were more symptomatic than patients with concordant moderate AS,” the researchers added.
Men made up the majority for paradoxical (51.8%) and classical 66%) but not normal-flow, low-gradient (42.3%).
Significantly higher mortality rates for discordant patients
During the median 50-month follow-up period (interquartile range [IQR]: 24 to 82 months), 874 (44%) patients died.
The 788 patients with discordant grading had significantly higher mortality rates than those with concordant moderate AS at 1-, 3- and 5-year follow-up (17% vs. 10%, 32% vs. 24% and 36% vs. 47%, respectively; P < 0.001).
Patients in the discordant group were less likely to undergo aortic valve replacement (AVR) at follow-up (17%) compared with patients in the concordant group (40%) (P < 0.001).
On multivariable analysis, paradoxical low-flow, low-gradient (hazard ratio [HR]: 1.458; 95% confidence interval [CI]: 1.072-1.983; P = 0.014) and classical low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality, the researchers said.
Yet, the normal-flow, low-gradient pattern accounted for the vast majority (55%) of discordant cases, whereas the classical low-flow, low-gradient pattern accounted for 31% and the paradoxical low-flow, low-gradient pattern for 14% of these cases.
“Interestingly, when only considering patients with preserved LVEF (≥50%) or preserved SVi (≥35 mL/m2), patients with discordant moderate AS still showed worse outcomes compared with patients with concordant moderate AS,” the researchers added.
Overall, “these findings underscore the need to better phenotype patients with discordant moderate AS,” they stressed.
They also called for prospective trials to determine whether AVR at an earlier stage would be beneficial in patients with classical and paradoxical low-flow, low-gradient moderate AS.
Updating the guidance
In an accompanying editorial, Jae K. Oh, MD, and Saki Ito, MD, MSc, from Mayo Clinic, Rochester, Minnesota, highlighted a mismatch between the historic basis for clinical recommendations in AS and real-life AS practice today.
“Our clinical decision to treat patients with AS is primarily based on their symptoms when AS is severe as currently defined. The recommendation stems from the historical retrospective review of 10 patients who died of severe AS in 1968,” said the editorialists.
“Their average age of symptomatic onset was 60 years, and the average age of 63 years for the death; they are very different from the patients we manage in our current practice where AS frequently coexists with comorbidities.”
They stressed that assessment of the contribution of underlying myocardial disease vs. AS will be critical in assessing whether AVR could benefit a patient who is symptomatic with AVA <1.5 cm2.
“The current study demonstrates that reduced stroke volume or SVi is an important prognostic factor,” they continued.
“Management of the underlying conditions responsible for reduced stroke volume, if possible, is as important as AVR to improve patients’ long-term outcomes.”
Stassen J, Ewe SH, Singh GK, et al. Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis. J Am Coll Cardiol 2022;80:666-676.
Oh JK, Ito S. Severity of Aortic Stenosis: A Moving Target. J Am Coll Cardiol 2022;80:677-680.
Image Credit: Yurii Kibalnik – stock.adobe.com