Comprehensive risk assessment in patients with pulmonary arterial hypertension referred for lung transplantation: a single-center experience

Abstract

Abstract Background Current guidelines recommend risk stratification to optimize the timing to refer patients with pulmonary arterial hypertension (PAH) for lung transplantation (LT). However, the optimal timing for referral may vary by country. It is unknown whether risk stratification could be helpful to predict the post-referral outcome in Japan where the waiting period is about 3 years. Purpose We aimed to investigate the predictive value of risk stratification at the LT referral time, and to provide a decision-making tool to refer patients for LT. Methods We performed a retrospective cohort study of consecutive PAH patients referred for LT from May 2014 to December 2021. Risk status was assessed by the ESC/ERS three-strata and four-strata model (Figure 1). For assessment, functional class, six-minute walk distance, brain natriuretic peptide, the ratio of TAPSE to PASP, mean right atrial pressure and cardiac index were used as variables. In the exploratory analysis, the intermediate risk group by the three-strata model was further divided into two groups based on the median proportion of low-risk variables (modified risk assessment): low-intermediate or high-intermediate risk. The primary outcome was all-cause mortality after referral. Results 52 patients were enrolled [median age 30.5 (22.0-40.0) years, 83% idiopathic/heritable PAH]. During a median follow-up period of 2.5 (1.8-3.4) years, 9 patients died, and 13 patients underwent LT. By the three-strata model, 15, 36, and 1 patients were classified as low-, intermediate- and high risk (Figure 2a). There was no significant difference in survival between low- and intermediate risk. By the four-strata model, 33, 16, and 3 patients were classified as low-intermediate-, high-intermediate and high risk (Figure 2b). The four-strata model identified high-risk patients with survival rates of 33% at 1 year, whereas did not discriminate survival between low-intermediate and high-intermediate risk. By the modified risk assessment, 15, 28, 8 and 1 patients were classified as low-, low-intermediate, high-intermediate and high risk (Figure 2c). Patients at high-intermediate risk or higher had significantly worse survival (P<0.001); survival rates at 3 years were 92%, 80% and 34% in the low-, low-intermediate, and high-intermediate or high-risk group, respectively. In Cox regression analysis, high-intermediate or high risk by the modified risk assessment was significantly associated with the primary outcome adjusted for age, sex and PAH etiologies (HR, 6.284; 95% CI, 1.743-22.662; p=0.005). Conclusion The prognosis of high-risk group by the four-strata model was too poor to survive the waiting period. Whereas, the modified risk assessment could discriminate patients who could continue medical therapy or should be referred for LT. Risk stratification could help clinicians to make decisions to refer patients for LT. Further work is needed to refine the assessment tool in the context of LT referral.