Hemodynamic correlates of RV afterload and pulmonary artery pulsatility under treatment with prostacyclin: retrospective analysis of changes from baseline in pulmonary arterial hypertension patients

Abstract

Purpose: Survival in PAH is significantly dependent on right ventricular function. We characterized the change from baseline in hemodynamic correlates of right ventricular (RV) afterload which reflects the arterial load to steady flow, and includes transpulmonary gradient (TPG), pulmonary vascular resistance (PVR), and diastolic pulmonary vascular pressure gradient (DPG), and parameters of oscillatory load, including pulmonary arterial compliance (PAC), upstream impedance (Zup), pulmonary valve resistance (Zva), and fractional pulse pressure (FPP). Methods: Univariate proportional hazards regression model using cubic spine function was constructed to assess the effects of parameters on death and lung transplantation among 933 PAH randomized patients from United Therapeutics (UT) prospective database. Receiver operating characteristic (ROC) analysis was used to assess the optimal hemodynamic cut-offs. Results: Within 12 weeks parameters of oscillatory load did not change, while PVR was significantly reduced in patients on treprostinil compared to placebo (Mean, [95%C.I.]: -2.6WU [-4.2, -1.0]). Because of the fixed time constant in the relation between resistance and compliance, PVR threshold for a significant change in pulsatile parameters was assessed. ROC analysis revealed that PVR has to be reduced by at least 3WU to achieve an improvement in Zva, (area under the curve [AUC]: 0.84), whereas an increase in PAC is already reached after a reduction of 1WU (AUC: 0.90). However, only baseline PVR (p<0.001) and Zva (p<0.001) were predictors of survival/freedom of lung transplantation. Patients with improved PAC and Zva had a larger reduction in afterload (AmPAP (mmHg) -3±7.8, -3.6±7.7; APVR (WU): -3.1±4.5, -3.0±4.6) than patients with worsened PAC and Zva (AmPAP (mmHg): 2.2±8.1, 2.2±8.2; APVR (WU): 2.5±4.5; 2.1 ±4.7). Conclusion: PVR is the key steady flow parameter that is changed under treatment with treprostinil, while parameters of pulsatility did not change significantly over 12 weeks. Baseline PVR (p<0.001) and Zva (p<0.001) were predictors of survival/freedom of lung transplantation. The data show that a minimum improvement of 3WU for PVR is essential to reach a decrease of pulmonary valve resistance Zva.