ObjectivesUpright computed tomography (CT) can detect slight changes particularly in the superior vena cava (SVC) volume in healthy volunteers under the influence of gravity. This study aimed to evaluate whether upright CT-based measurements of the SVC area are useful for assessing mean right atrial pressure (mRAP) in patients with heart failure.MethodsWe performed CT in both standing and supine positions to evaluate the SVC (directly below the junction of the bilateral brachiocephalic veins) and inferior vena cava (IVC; at the height of the diaphragm) areas and analyzed their relationship with mRAP, measured by right heart catheterization in 23 patients with heart failure.ResultsThe median age of enrolled patients was 60 (51−72) years, and 69.6% were male. The median mRAP was 3 (1−7) mmHg. The correlations between the standing position SVC and IVC areas and mRAP were stronger than those in the supine position (SVC,ρ= 0.68,p< 0.001 andρ= 0.43,p= 0.040; IVC,ρ= 0.57,p= 0.005 andρ= 0.46,p= 0.026; respectively). Furthermore, the SVC area in the standing position was most accurate in identifying patients with higher mRAP (> 5 mmHg) (SVC standing, area under the receiver operating characteristic curve [AUC] = 0.91, 95% confidence interval [CI], 0.77–1.00; SVC supine, AUC = 0.78, 95% CI, 0.59–0.98; IVC standing, AUC = 0.77, 95% CI, 0.55–0.98; IVC supine, AUC = 0.72, 95% CI, 0.49–0.94). The inter- and intraobserver agreements (evaluated by intraclass correlation coefficients) for all CT measurements were 0.962–0.991.ConclusionsUpright CT-based measurement of the SVC area can be useful for non-invasive estimation of mRAP under the influence of gravity in patients with heart failure.Key Points• This study showed that the superior vena cava (SVC) area in the standing position was most accurate in identifying patients with heart failure with higher mean right atrial pressure.• Upright computed tomography-based measurements of the SVC area can be a promising non-invasive method for estimating mean right atrial pressure under the influence of gravity in patients with heart failure.• Clinical management of patients with heart failure based on this non-invasive modality may lead to early assessment of conditional changes and reduced hospitalization for exacerbation of heart failure.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-022-09360-8.