Recent controversies regarding the prevalence of pulmonary hypertension (PH) in patients with sickle cell disease (SCD) have been raised. 1 While the prevalence of PH differed among several SCD cohorts, 2-4 the reported range of 6-11% is higher than the general population and those with HIV or scleroderma. 1 PH in SCD is often complicated by concurrent left ventricular (LV) diastolic dysfunction and anemia-related changes in hemodynamics. The change in pressure across the pulmonary circulation as reflected by the transpulmonary pressure gradient (TPG) can be measured during right heart catheterization (RHC). TPG is less clouded by anemia-related adaptations than pulmonary vascular resistance (PVR), the more conventional indicator of pulmonary vascular disease. We have shown that elevation in the TPG is associated with increased mortality, but did not explore the relationship of TPG to functional capacity in our previous analyses. 4 While the morphologic cardiac manifestations of sickle cell associated cardiomyopathy5-8 and rare left ventricular systolic dysfunction9 have been described, there have been no reports using cardiac magnetic resonance (CMR) imaging in conjunction with invasive hemodynamics to understand the relationship of TPG and right ventricular (RV) remodeling in patients with SCD. Accordingly, we performed a new hypothesis-generating analysis to assess the relationship of RHC-derived TPG and CMR-derived RV remodeling in patients with SCD. We also investigated the significance of using a TPG threshold and evidence of RV dysfunction to identify patients with overall poor outcomes. Detailed patient enrollment criteria of the Bethesda Sickle Cell Cohort and haematologica 2016; 101: e40