Linking Energetic Inefficiency to Ventriculoarterial Uncoupling in Pulmonary Hypertension

Right ventricular-pulmonary arterial (RV-PA) uncoupling is central to prognosis in precapillary pulmonary hypertension (PH). While the tricuspid annular plane systolic excursion tosystolic pulmonary artery pressure (TAPSE/sPAP) ratio is an established bedside surrogate of RV-PA coupling, novel energetic markers such as three-dimensional (3D)-derived right ventricular (RV) global wasted work (GWW) may provide complementary insight into maladaptive RV remodeling.

To contextualize the prognostic value of RV GWW relative to TAPSE/sPAP and clarify their mechanistic and clinical complementarity.

Patients with elevated GWW (≥38 mmHg/%) exhibited evidence of RV-PA uncoupling, including a reduced RV end-systolic elastance to arterial elastance (E_es/E_a) ratio (0.47 [0.34-0.73] vs. 0.71 [0.50-0.91]; p = 0.007) and lower TAPSE/sPAP ratio (0.21 [0.18-0.32] vs. 0.34 [0.22- 0.45] mm/Hg; p = 0.003) compared with lower GWW. In secondary analyses, a TAPSE/sPAP ratio below the median was associated with increased risk of death or lung transplantation (hazard ratio [HR] 3.20; 95% CI: 1.45-7.08), remaining significant after adjustment for age and sex (adjusted HR 2.97; 95% CI: 1.27-6.94). Discrimination was modest and comparable for TAPSE/sPAP (C-statistic 0.63; 95% CI: 0.53-0.73) and GWW (C-statistic 0.61), with no significant difference between metrics (ΔC = -0.02; p = 0.68).

TAPSE/sPAP remains a robust and clinically valuable surrogate of macroscopic RV-PA coupling. However, GWW offers complementary information by quantifying myocardial inefficiency related to paradoxical and postsystolic deformation, capturing energetic consequences of afterload mismatch that may not be reflected by displacement-based indices alone. Integrating energetic and mechanical markers may enable a more granular assessment of RV performance, particularly in intermediate-risk PH, and warrants evaluation in larger multicenter studies.