In patients with aortic stenosis (AS), it has been reported that the transvalvular pressure gradients (APs) may be reduced or even abolished in the presence of concomitant arterial hypertension, but the mechanisms underlying this phenomenon remain unclear. The study aim was to: (i) examine the relationship between systemic arterial hemodynamics and the peak-to-peak (deltaP(PtoP)), peak deltaP and mean deltaP; and (ii) propose and validate a new formula for the non-invasive estimation of the deltaP(PtoP) and of the peak left ventricular systolic pressure (LVSP) using Doppler echocardiography. Two fixed stenoses (geometric orifice area 1.0 and 1.35 cm2) and one bioprosthesis (effective orifice area (EOA) 1.2 cm2) were tested in a mock flow circulation model. Systemic vascular resistance (R) was increased from 1,500 to 3,300 dyne.s/cm5, and systemic arterial compliance (C) was decreased from 2.9 to 0.9 ml/mmHg, while transvalvular flow was held constant. Neither C nor R had any significant impact on EOA, peak deltaP and mean deltaP. deltaP(PtoP) was decreased markedly, however, when C was reduced (bioprosthesis: -15 mmHg (-69%); orifice 1.35 cm2: -24 mmHg (-30%); cm2: (-13%)). Subsequently, an equation was proposed to predict deltaP(PtoP) from EOA, mean deltaP, and C measured by Doppler echocardiography. LVSP calculated by adding the predicted deltaP(Ptop) to systolic arterial pressure (SAP) was compared with LVSP measured directly in a dataset of 24 pigs with experimentally induced AS. There was a strong agreement between the estimated and measured LVSP (r = 0.97; mean absolute error 5 +/- 5 mmHg). deltaP(Ptop) should not be used to evaluate AS severity because, as opposed to peak and mean deltaPs, it is highly influenced by C. The new non-invasive method proposed in this study to estimate the LVSP may be useful for obtaining a more accurate estimate of global LV afterload in patients with AS.