Early risk response to vasodilators and outcomes in interstitial lung disease associated pulmonary hypertension

BACKGROUND Pulmonary hypertension (PH) commonly complicates interstitial lung disease (ILD) and is associated with poor prognosis. Although pulmonary vasodilators may improve clinical parameters, they can also cause severe hypoxemia; thus, reliable noninvasive tools are needed to assess treatment response. We investigated whether changes in four-stratum risk stratification category before and after vasodilator therapy are associated with prognosis in patients with ILD-PH. METHODS Clinical data before and after vasodilator therapy were retrospectively collected from consecutive patients with ILD-PH at a single ILD-specialty center in Japan between May 2007 to September 2023. Four-stratum risk stratification was performed using World Health Organization functional class, brain natriuretic peptide or N-terminal pro-brain natriuretic peptide, and 6-min walk distance. Cox proportional hazard analyses adjusted for ILD-gender-age-physiology index, mean pulmonary arterial pressure, and time from PH diagnosis to pulmonary vasodilator therapy were used to evaluate associations between risk stratification and transplant-free survival. RESULTS Among 64 patients, 6 were categorized as low risk, 30 as intermediate-low risk, 21 as intermediate-high risk, and 7 as high risk. Vasodilator therapy improved pulmonary hemodynamics and led to improvement in risk category in 9 patients and deterioration in 14. Post-treatment risk stratification provided good prognostic discrimination. Multivariate Cox analysis showed that post-treatment risk scores were independently associated with transplant-free survival (adjusted HR 3.286, 95% CI 1.897-6.258). CONCLUSIONS Post-treatment four-stratum risk stratification was associated with transplant-free survival in patients with ILD-PH.