Normal flow low gradient aortic stenosis - disenchanting the myth

Introduction:

Normal flow low gradient aortic stenosis (AS) with both aortic valve area < 1 cm² and mean pressure gradient < 40 mmHg despite normal stroke volume (SV) index is judged unlikely to be severe AS by current guidelines. Therefore, conservative treatment is recommended. But pressure gradient physically depends on flowrate which is SV per ejection time. Hence, patients might have low flow condition despite normal SV. Thus, functional testing like dobutamine stress echo (DSE) can be reasonable. Furthermore, pitfalls in assessing SV by echo might lead to its overestimation. Both could result in missing symptomatic severe AS.

Methods:

We retrospectively screened for patients admitted to our center between 2019 and 2023 for suspected higher grade AS. Only patients whose diagnostic workup included DSE were included into this study. AS was classified into classical low flow low gradient (clflg), paradoxical low flow low gradient (plflg) or normal flow low gradient (nflg) accordingly. Patients were judged by DSE as having fixed severe AS when highest mean pressure gradient >40 mmHg or pressure gradient changed >20 mmHg to baseline and in patients with final flow rate < 250 ml/s when projected valve opening area was <1 cm². We compared non-invasive SV estimation by echo with invasive SV estimation by right heart catheterization. Also, discrepancies of non-invasive SV calculation using LVOT measured by echo with LVOT estimated by body surface area were assessed. Continuous parameters are expressed as mean ± standard deviation and as number and percentage of total in case of frequencies. Difference in means was tested by Welch's test because heteroskedasticity was found and post-hoc analysis for between group differences was done by Dunnett’s Test.

Results:

In the study period 210 patients with mean age of 80±7 years, 49% of female sex and most frequently complaining dyspnea (91% of cases with NYHA II-IV) were selected (clflg n=101, plflg n=65 and nflg n=44). Baseline valve opening area was 0.73±0.15cm² in clflg, 0.77±0.13cm² in plflg and 0.9± 0.11cm² in nflg with mean pressure gradient of 18±6mmHg in clflg, 20±7mmHg in plflg and 22±7mmHg in nflg. The mean baseline flowrate was 150±36ml/s in clflg, 192±44ml/s in plflg and 240±70ml/s in nflg. 24/40 (60%) in nflg patients showed flowrate <250ml/s and therefore low-flow status. Evaluated by DSE 27/44 (61.7%) of nflg patients showed pattern of fixed AS. Mean discrepancy between baseline flowrate calculated by measured vs. estimated LVOT was significantly different between groups with moderate to high effect strength (p-value of<0.001, Eta² 0.137) and highest in nflg (98.6±79ml/s, p=0.004) compared to lflg (50±42ml/s, p=0.003) and plflg (47.2±38ml/s). Also mean non-invasive vs. invasive SV difference between groups diverged significantly, effect strength was high (p-value of<0.001, Eta² 0.283) with around cero in lflg (-0.08±7.9ml) and plflg (-0.7±5.8ml) but 13.4±15ml in nflg.

Conclusion:

Using a flowrate-based assessment in nflg patients a relevant portion of patients might show features of severe AS. Overestimation of SV and flowrate in baseline compared to invasive SV estimation or using estimated LVOT could be an underlying cause of misclassifying patients to having normal flow condition. As these data were collected in a selected cohort of a tertiary center in mainly symptomatic patients, generalization to other populations is limited.