High Heart Rate and Pulmonary Vascular Resistance Predict Poor Prognosis after Referral for Lung Transplantation in Patients with Pulmonary Arterial Hypertension

Abstract

Purpose Recent progress in the treatment of pulmonary arterial hypertension (PAH) such as high-dose epoprostenol and upfront combination therapy brought a marked improvement in prognosis of PAH. However, severely ill cases with PAH still need lung transplantation. Considering the first-come-first-served system and resulting long waiting period Japan, the timing of referral for lung transplantation is critical. Methods Consecutive 31 patients with PAH (including pulmonary veno-occlusive disease) referred to our hospital to be considered eligibility for lung transplantation were enrolled in this study. We retrospectively analyzed patients’ characteristics at referral for lung transplantation and their clinical outcomes. Results Seventeen of 31 patients (55%) were female and average age at referral was 30.6±11.8 year-old. Twenty-six patients were idiopathic/heritable PAH, 4 were connective tissue disease associated PAH and 1 was pulmonary veno-occlusive disease. They were referred to our hospital 2127±1691 days after diagnosis. All but one patients were introduced parenteral prostanoid. Mean received dose of parenteral prostanoid was 98±56 ng/kg/min at referral. Although their mean pulmonary artery pressure was severely elevated (51.1±11.6 mmHg), cardiac index and six-minute walk distance were relatively maintained (3.63±0.98 L/min/m2 and 394±174m, respectively). Two patients were not registered as candidates for lung transplantation for medical or social reason. Three patients underwent successful lung transplantation, while eight patients died on the waiting list. Three-year survival after referral was 67% in total. Multivariate analysis revealed that heart rate (HR) and pulmonary vascular resistance (PVR) were independent predictors of all-cause mortality after referral (p=0.016 and p=0.016, respectively). Conclusion High HR and PVR are independent predictors of mortality in patients with PAH receiving parenteral prostanoid and awaiting lung transplantation. Although high-dose parenteral prostanoid improved hemodynamics in patients with PAH, the high output status and relatively maintained exercise capacity might have delayed referral for lung transplantation.