The influence of increased venous return on right ventricular dyssynchrony during acute and sustained hypoxaemia

New Findings What is the central question of this study? Right ventricular dyssynchrony is a marker of function that is elevated in healthy individuals exposed to acute hypoxia, but does it remain elevated during sustained exposure to high altitude hypoxia, and can it be normalised by augmenting venous return? What is the main finding and its importance? For the first time it is demonstrated that (i) increasing venous return in acute hypoxia restores the synchrony of right ventricular contraction and (ii) dyssynchrony is evident after acclimatisation to high altitude, and remains sensitive to changes in venous return. Therefore, the interpretation of right ventricular dyssynchrony requires consideration the prevailing haemodynamic state. Abstract Regional heterogeneity in timing of right ventricular (RV) contraction (RV dyssynchrony; RVD) occurs when pulmonary artery systolic pressure (PASP) is increased during acute hypoxia. Interestingly, RVD is not observed during exercise, a stimulus that increases both PASP and venous return. Therefore, we hypothesised that RVD in healthy humans is sensitive to changes in venous return, and examined whether (i) increasing venous return in acute hypoxia lowers RVD and (ii) if RVD is further exaggerated in sustained hypoxia, given increased PASP is accompanied by decreased ventricular filling at high altitude. RVD, PASP and right ventricular end‐diastolic area (RVEDA) were assessed using transthoracic two‐dimensional and speckle‐tracking echocardiography during acute normobaric hypoxia ( = 0.12) and sustained exposure (5–10 days) to hypobaric hypoxia (3800 m). Venous return was augmented with lower body positive pressure at sea level (LBPP; +10 mmHg) and saline infusion at high altitude. PASP was increased in acute hypoxia (20 ± 6 vs. 28 ± 7, P < 0.001) concomitant to an increase in RVD (18 ± 7 vs. 38 ± 10, P < 0.001); however, the addition of LBPP during hypoxia decreased RVD (38 ± 0 vs. 26 ± 10, P < 0.001). Sustained hypoxia increased PASP (20 ± 4 vs. 26 ± 5, P = 0.008) and decreased RVEDA (24 ± 4 vs. 21 ± 2, P = 0.042), with RVD augmented (14 ± 5 vs. 31 ± 12, P = 0.001). Saline infusion increased RVEDA (21 ± 2 vs. 23 ± 3, P = 0.008) and reduced RVD (31 ± 12 vs. 20 ± 9, P = 0.001). In summary, an increase in PASP secondary to acute and sustained exposure to hypoxia augments RVD, which can be at least partly reduced via increased venous return.