Appropriate normalization methods to scale Doppler-derived stroke volume (SV) in patients with aortic stenosis (AS) are poorly defined and reference values are lacking. We aim to establish reference values for normalized SV, to compare the prognostic value of SV normalized by different methods in AS and to examine the outcome of low-flow(LF) low-gradient(LG) AS with preserved ejection fraction(LVEF) based on newly defined reference values.

In 2781 normotensive adults without cardiovascular disease we defined normal relationships between SV and body size by nonlinear regression. We analyzed the prognostic performance of ratiometric and allometric normalized SV in 1450 patients with severe AS and preserved LVEF.

The allometric exponents that described the SV-height (H) and SV-body surface area (BSA) relationships were 1.32 and 0.88, respectively. In males, LF reference values were:<28ml/m²,<30ml/m,<30ml/(m²)^0.88, and, respectively,<26ml/m^1.32, and in females<27ml/m²,<28ml/m,<29ml/(m²)^0.88, and, respectively,<24ml/m^1.32. In patients with severe AS, SV/H^1.32 was most consistently associated with mortality and showed better prognostic performance than other normalized SV parameters. Compared to H-normalization, BSA-normalization markedly overestimated the frequency of LF(3% vs. 9%). In 1354 AS patients managed initially medically, LF/LG AS defined based on the 35ml/m² cut-off showed better outcome than high gradient(HG) AS (adjusted HR 0.85[0.62–0.96]). When new reference values were used, the mortality risk of LF/LG AS was higher than that of HGAS (adjusted HR 1.37[1.06–1.89] for SV/BSA and adjusted HR 1.42[1.10–2.15] for SV/H^1.32).

We provide reference values and appropriate normalization methods for SV by Doppler-echocardiography. Patients with LG severe AS, preserved LVEF and “true” LF are at high-risk of death during follow-up. (Fig. 1)