The association between soluble ST2 and transplant-free survival in precapillary pulmonary hypertension

Soluble ST2 (sST2) is a decoy receptor for interleukin-33 and a prognostic biomarker in heart failure, but its utility in precapillary pulmonary hypertension (PH) is not well established. Therefore, we aimed to evaluate the prognostic value of sST2 in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) at diagnosis and follow-up.

In this prospective observational cohort study, we measured plasma sST2 by sandwich enzyme-linked immunosorbent assay in samples taken at diagnostic right heart catheterization from 202 treatment naïve Norwegian patients with precapillary PH (n = 115 with PAH, n = 87 with CTEPH). In an external validation cohort, we included 185 treatment naïve Swedish patients with precapillary PH (n = 121 with PAH, n= 64 with CTEPH). In a subset of patients, we measured sST2 levels at follow-up in the Norwegian discovery cohort (n=63) and the Swedish validation cohort (n=121).

On univariable Cox regression, log sST2 was firmly associated with transplant-free survival in the Norwegian discovery cohort (HR 1.92, P = 0.005) and in the Swedish validation cohort (HR 2.64, P <.001). When adjusting for age and NT-proBNP, sST2 levels were no longer significantly associated with transplant-free survival in the discovery cohort, while remaining independently associated with the outcome in the validation cohort. The change in sST2 from baseline to follow-up was not associated with transplant-free survival in either cohort.

Plasma sST2 levels were univariably associated with death or lung transplantation in PAH and CTEPH but were no longer prognostic after adjustment for age and NT-proBNP. The change in sST2 from baseline to follow-up did not predict transplant-free survival.