Differential Right Ventricular Afterload during Exercise in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Background: 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). Methods: Fifty-seven IPAH patients and 227 CTEPH patients 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. Results: CTEPH patients were older, had a lower TAPSE/systolic PAP ratio compared to IPAH patients. At both rest and peak exercise, CTEPH patients demonstrated higher PAWP, and lower SaO₂, and cardiac output than IPAH patients. 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, p<0.001; peak: 1.8 [1.3, 2.2] vs. 2.4 [1.8, 2.8] mL/mmHg, p<0.001), as was the resistance compliance (RC) time constant (rest: 0.37 [0.29, 0.44] vs. 0.50 [0.40, 0.64] sec, p<0.001; peak: 0.23 [0.19, 0.29] vs. 0.34 [0.24, 0.40] sec, p<0.001). The PVR-PAC curve in CTEPH was leftward-shifted compared to IPAH (p<0.001). In both groups, the PVR-PAC curve in peak exercise shifted further leftward compared to rest (p<0.001). Conclusion: Despite similar PVR levels, CTEPH patients experience greater afterload to RV from rest to exercise compared to those with IPAH, revealing subtype-specific differences in RV afterload.