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Prognostic Implications of Discordant Low-Gradient Severe Aortic Stenosis
Quick Takes
- Using prospectively acquired echo/Doppler data and retrospective assessment of survival, the 5-year survival of patients with moderate aortic stenosis (AS) (58.9%) was better than for patients with discordant low-gradient (DLG) severe AS (47%) or high-gradient (HG) severe AS (41.2%, p < 0.001), with a pattern that was similar in unoperated patients (54.1% vs. 37.9% vs. 28.1%, p < 0.001).
- At comparable mean gradient (MG), a lower aortic valve area index (AVAi) was associated with a worse prognosis, whereas at comparable AVAi, a higher MG was associated with a worse the prognosis.
- The DLG severe AS study population included a mixture of patients with low flow (about one third) and normal flow (about two thirds); the observation that survival of patients with DLG AS was intermediate between moderate AS and HG severe AS could simply reflect the heterogeneity of the group rather than the prognosis of a discrete subset of patients.
Study Questions:
Compared to patients with high-gradient (HG) severe aortic stenosis (AS), what are the outcomes of patients with discordant low-gradient (DLG) severe AS?
Methods:
The BEL-F-ASt (Belgium-France-Aortic Stenosis) registry includes consecutive adult patients with at least mild AS diagnosed at one of three tertiary hospital echocardiography laboratories between 2000 and 2020; after exclusions (including congenital AS, subvalvular left ventricular [LV] outflow obstruction, LV ejection fraction [LVEF] <50%, advanced renal disease, and absence of follow-up), there were 2,582 patients in the overall population and 1,812 unoperated patients. AS was categorized as moderate AS (aortic valve area index [AVAi] ≥0.6 cm2/m2, mean gradient [MG] ≤40 mm Hg; n = 876), DLG severe AS (AVAi <0.6 cm2/m2, MG ≤40 mm Hg; n = 933), or HG severe AS (MG ≥40 mm Hg, AVAi <0.6 mm2/m2; n = 773). The index echocardiogram was taken as time 0; follow-up was retrospectively assessed and censored at the time of surgery. The study endpoint was all-cause mortality; survival was compared overall and after matching (inverse probability weighting and propensity-score matching) for clinical and imaging variables.
Results:
After inverse probability weighting-matching, the three groups were balanced. Five-year survival was better in moderate AS than in DLG severe AS and HG severe AS patients (58.9% vs. 47% vs. 41.2%, p < 0.001). Similar results were obtained in unoperated patients (54.1% vs. 37.9% vs. 28.1%, p < 0.001). To explore the impact of MG (≤40 vs. >40 mm Hg) and AVAi (<0.6 vs. ≥0.6 cm2/m2) on outcomes, survival of propensity score-matched cohorts of HG severe AS vs. DLG severe AS and moderate AS vs. DLG severe AS were compared. After matching for MG, survival was better in moderate AS than in DLG severe AS (52% vs. 40%, p < 0.001) and directly related to AVAi (smaller AVAi was associated with worse survival). After matching for AVAi, survival was better in DLG severe AS than in HG severe AS (45% vs. 33%, p < 0.001) and inversely related to gradient (higher gradient was associated with worse survival).
Conclusions:
Survival of patients with DLG severe AS is better than that of HG severe AS and worse than that of patients with moderate AS. At comparable MG, a lower AVAi is associated with a worse prognosis, whereas at comparable AVAi, a higher MG is associated with a worse prognosis. The authors conclude that these data argue that DLG severe AS is an intermediate form in the AS disease continuum.
Perspective:
Many patients evaluated for AS have discordant echo/Doppler data, most commonly with AVAi suggestive of more severe AS than that predicted by MG. Some of those patients have truly severe AS, whereas others probably have less than severe AS but have measurement error leading to the underestimation of echo/Doppler AVAi. LG severe AS is best characterized by LV stroke volume index (SVi) as either low flow (LF; LV SVi <35 mL/m2) or normal flow (NF; LV SVi ≥35 mL/m2). The current ACC/AHA guideline on valvular heart disease has specific management recommendations for patients with LF-LG severe AS with normal LVEF (termed paradoxical LF AS, stage D3 AS if symptomatic); however, probably owing to a more heterogenous group that includes many patients with less than severe AS, data for patients with NF-LG AS are more heterogeneous and guideline recommendations are lacking.
The present study attempts to address the outcomes of patients with LG severe AS and normal LVEF (termed ‘DLG severe AS’ in this study), with findings that survival is between that for patients with HG severe AS and that for patients with moderate AS. However, only about a third of the patients had documentation of LF (the majority of patients therefore having NF-LG AS), suggesting that the study population with ‘DLG severe AS’ might well have been a mixture of patients with LF-LG severe AS, NF-LG severe AS, and patients without severe AS. As such, the observation that survival was intermediate could simply reflect the heterogeneity of the group rather than the prognosis of a discrete subset of patients.
Clinical Topics: Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound
Keywords: Aortic Valve Stenosis, Cardiac Surgical Procedures, Diagnostic Imaging, Echocardiography, Echocardiography, Doppler, Geriatrics, Heart Valve Diseases, Prognosis, Stroke Volume, Survival
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