Follow-Up Functional Class and 6-Minute Walk Distance Identify Long-Term Survival in Pulmonary Arterial Hypertension

Guidelines recommend specific treatment goals for pulmonary arterial hypertension (PAH) patients: functional class I or II, 6-min walk distance (6MWD) ≥ 380 to 440 m, normal natriuretic peptide levels, and normal right-sided invasive hemodynamics. Only observational registry data support this recommendation. Our aim was to test these goals in a large group 1 PAH cohort against long-term survival.

We analyzed the PHIRST and TRIUMPH populations (n = 563, age 53.5 ± 14.7 years, female sex 79%). The predictor variables were the treatment goals measured at the end of the placebo-controlled phase (16 and 12 weeks, respectively). The primary outcome was all-cause mortality at the end of follow-up during the open-label extension phase.

There were 73 deaths during median follow of 1072 days (range 27 to 2177). Patients who achieved a functional class I or II had better survival. Both a 6MWD ≥ 380 m and ≥ 440 m were associated with lower mortality, but survival was better in patients able to walk ≥ 440 m. The best long-term survival was achieved with functional class I or II and 6MWD ≥ 440 m. In a subset of the population, cardiac index > 2.5 L/min/m² was weakly associated with better survival.

WHO functional class I or II, 6MWD ≥ 440 m and CI > 2.5 L/min/m² measured 12-16 weeks after the introduction of PAH-targeted therapy are associated with better long-term survival in PAH. Best survival is observed by reaching both the functional class and the 6MWD goals.