Background: “Low-risk” pulmonary arterial hypertension (PAH) patients are defined as having a risk of death <5% within 1 year. As treatment improves, accounting for the negative impact of short-term morbidity and considering extending the duration of <5% mortality in this definition seem prudent.
Objectives: This study sought to propose a more stringent definition of low risk that extends the low mortality risk to 3 years and specifies a low risk of morbidity at 1 year.
Methods: This study used patient-level data from a harmonized data set of 8 PAH randomized controlled trials that included patients with a REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) 2.0 risk score ≤6 (ie, low risk using contemporary scores). Low risk was a priori defined as “risk of death <5% at 3 years and risk of clinical worsening <10% at 1 year.” Clinical worsening was defined at the individual trial level and included any of the following: lung transplantation, hospitalization for PAH, initiation of long-term oxygen therapy, 15% decrease in 6-minute walking distance (6MWD) from baseline with a worsening of NYHA functional class, or the addition of a new PAH medication.
Results: A total of 1,925 PAH patients were included: median age, 46 years (Q1-Q3: 34-57 years); mean pulmonary artery pressure, 47 mm Hg (Q1-Q3: 37-58 mm Hg); pulmonary vascular resistance, 8 WU (Q1-Q3: 6-12 WU), 6MWD, 409 m (Q1-Q3: 363-423 m); and N-terminal pro–B-type natriuretic peptide, 227 pg/mL (Q1-Q3: 101-621 pg/mL). Compared with patients with a REVEAL 2.0 score equal to 5 or 6, patients with a score ≤4 had a better clinical and hemodynamic presentation and met the definition of “refined low risk” (3-year mortality of 2.6% and 1-year clinical worsening of 6.4%). Idiopathic PAH, 6MWD, N-terminal pro–B-type natriuretic peptide, NYHA functional class I to II, heart rate, and the absence of previous atrial fibrillation were associated with refined low risk.
Conclusions: This study is the first to embed both morbidity and mortality within the definition of low -risk for PAH and suggests that patients with a REVEAL 2.0 risk score ≤4 define this condition.
Editors
JACC Heart Failure Editor-in-Chief
Biykem Bozkurt, MD, PhD, FACC
Deputy Editor
Akshay S. Desai, MD, MPH
JACC Heart Failure CME/MOC Editor
Kenneth A. Ellenbogen, MD
Authors
Raymond Benza, MD
Charles Fauvel, MD, PhD
Important Dates
Date of Release: August 3, 2026
Term of Approval/Date of CME/MOC Expiration: August 2, 2027