Differential right ventricular afterload during exercise in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC)-the two primary components of right ventricular (RV) afterload-are interdependent and exhibit an inverse relationship. However, their variations across pulmonary hypertension subtypes and between rest and exercise remain unknown. We aimed to investigate the PVR-PAC relationship at rest and during exercise in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Fifty-seven patients with IPAH and 227 patients with CTEPH with near-normal mean pulmonary artery pressure (PAP; <30 mmHg) and pulmonary artery wedge pressure (PAWP; <15 mmHg) at rest underwent a symptom-limited exercise test using a supine cycle ergometer with right heart catheterization. Patients with CTEPH were older and had a lower TAPSE/systolic PAP ratio compared with patients with IPAH. At both rest and peak exercise, patients with CTEPH demonstrated higher PAWP and lower [Formula: see text] and cardiac output than patients with IPAH. Despite no significant difference in PVR, PAC was lower in CTEPH (rest: 2.5 [1.9, 3.7] vs. 3.5 [2.6, 4.8] mL/mmHg, <i>P</i> < 0.001; peak: 1.8 [1.3, 2.2] vs. 2.4 [1.8, 2.8] mL/mmHg, <i>P</i> < 0.001), as was the resistance compliance (RC) time constant (rest: 0.37 [0.29, 0.44] vs. 0.50 [0.40, 0.64] s, <i>P</i> < 0.001; peak: 0.23 [0.19, 0.29] vs. 0.34 [0.24, 0.40] s, <i>P</i> < 0.001). The PVR-PAC curve in CTEPH was leftward-shifted compared with IPAH (<i>P</i> < 0.001). In both groups, the PVR-PAC curve in peak exercise shifted further leftward compared with rest (<i>P</i> < 0.001). Despite similar PVR levels, patients with CTEPH experience greater afterload to RV from rest to exercise compared with those with IPAH, revealing subtype-specific differences in RV afterload.<b>NEW & NOTEWORTHY</b> This study is the first to characterize exercise-induced changes in the PVR-PAC relationship in IPAH and CTEPH. Despite similar PVR, patients with CTEPH showed significantly lower PAC and RC time constant at rest and during exercise. A leftward shift in the inverse PVR-PAC relationship in CTEPH highlights the importance of assessing both PAC and PVR under stress for accurate clinical assessment and tailored management for each subtype of PH.