Abstract Funding Acknowledgements Type of funding sources: None. Background Hemodynamic forces (HDFs) are the forces exchanged between the blood and the myocardium. Estimation of their magnitude and alignment could be a novel marker of cardiac dysfunction. Purpose To describe left ventricular (LV) HDFs values and distribution in patients with heart failure with reduced ejection fraction (HFrEF) and to compare them with those of a group of healthy controls. Methods A cohort of 26 non-ischemic patients with an initial diagnosis of HFrEF was enrolled. All of them underwent basal 2D echocardiography evaluation. Off-line HDFs estimation using a dedicated software based on speckle-tracking echocardiography was conducted. HDFs were normalized for the LV volume and expressed as a percentage of the force of gravity. HDFs were assessed over the entire cardiac cycle, in systole and diastole, both in apex to base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs was evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio). HDFs of HFrEF patients were compared with those of 24 healthy volunteers. Results HFrEF patients showed smaller values of A-B HDFs during the entire cardiac cycle (5,2 ± 1,24% vs 12,3 ± 3,6%; p = 0,001), in systole (7,2 ± 2% vs 16,6 ± 6,3%; p = 0,001) and diastole (3,3 ± 0,8% vs 7,1 ± 3,6%; p = 0,001). Moreover, comparing HFrEF subjects with healthy volunteers , the former had lower L-S HDFs during the entire cardiac cycle (1,6 ± 0,4% vs 2 ± 0,7%; p= 0,022) and in systole (1,6 ± 0,5% vs 2,3 ± 0,8%; p = 0,003), while in diastole they showed inappropriate high values of L-S HDFs (1,7 ± 0,6% vs 1,8 ± 0,9%; p = 0,999). Consequently, HFrEF patients had higher values of L-S/A-B ratio during the entire cardiac cycle (32 ± 6,9 vs 15 ± 7,7; p = 0,001), in systole (23,5 ± 7,4 vs 14,7± 4,2; p = 0,001), but particularly in diastole (52 ± 10,8 vs 28 ± 13,6; p = 0,001), showing an important HDFs misalignment. Conclusion When compared with healthy controls, HFrEF patients presented intraventricular fluid alterations characterized by lower HDFs magnitude and a significant HDFs misalignment, especially in diastole. Further studies are needed to confirm these initial results and to assess the effects of therapy on these new parameters. Abstract Figure. Abstract Figure.