Implications of Mean Pulmonary Arterial Wedge Pressure Trajectories in Pulmonary Arterial Hypertension

Rationale The mean pulmonary arterial wedge pressure (mPAWP) is the critical hemodynamic factor differentiating group 1 pulmonary arterial hypertension (PAH) from group 2 pulmonary hypertension associated with left heart disease. Despite the discrepancy between the mPAWP upper physiologic normal and current PAH definitions, the implications of the initial mPAWP for PAH clinical trajectory are poorly understood. Objectives To model longitudinal mPAWP trajectories in PAH over 10 years and examine the clinical and hemodynamic factors associated with trajectory membership. Methods Adult patients with PAH with two or more right heart catheterizations were identified from a multiinstitution healthcare system in eastern Massachusetts. mPAWP trajectories were constructed via group-based trajectory modeling. Feature selection was performed in least absolute shrinkage and selection operator regression. Logistic regression was used to assess associations between trajectory membership, baseline characteristics, and transplant-free survival. Measurements and Main Results Among 301 patients with PAH, there were two distinct mPAWP trajectories, termed “mPAWP-high” (n = 71; 23.6%) and “mPAWP-low” (n = 230; 76.4%), based on the ultimate mPAWP value. Initial mPAWP clustered around median 12 mm Hg (interquartile range [IQR], 8–14 mm Hg) in the mPAWP-high and 9 mm Hg (IQR, 6–11 mm Hg) in the mPAWP-low trajectories (P < 0.001). After feature selection, initial mPAWP ≥12 mm Hg predicted an mPAWP-high trajectory (odds ratio, 3.2; 95% confidence interval, 1.4–6.1; P = 0.0006). An mPAWP-high trajectory was associated with shorter transplant-free survival (vs. mPAWP-low, median, 7.8 vs. 11.3 yr; log-rank P = 0.017; age-adjusted P = 0.217). Conclusions Over 10 years, the mPAWP followed two distinct trajectories, with 25% evolving into group 2 pulmonary hypertension physiology. Using routine baseline data, longitudinal mPAWP trajectory could be predicted accurately, with initial mPAWP ≥12 mm Hg as one of the strongest predictors.