Current evidence suggests that exercise training is beneficial in pulmonary arterial hypertension (PAH). Unfortunately, the standard supervised, hospital-based programs limit patient accessibility to this important intervention. Our proof-of-concept study aimed to provide insight into the usefulness of a prescribed walking regimen along with arginine supplementation to improve outcomes for patients with PAH. Twelve PAH patients (all women) in New York Heart Association (NYHA) functional class (FC) II (n = 7) or III (n = 5) and in stable condition for ≥ 3 months were enrolled. Patients performed home- and fitness-center- based walking at 65–75% heart rate (HR) reserve for 45 min, six sessions/week for 12 weeks. Concomitant L-arginine supplementation (6000 mg/day) was provided to maximize beneficial endothelial training adaptations. Cardiopulmonary exercise testing, 6-min walk testing (6MWT), echocardiography, laboratory studies, and quality of life (QoL) survey (SF-36) were performed at baseline and 12 weeks. Eleven patients completed the study (72 session adherence rate = 96 ± 3%). Objective improvement was demonstrated by the 6MWT distance (increased by 40 ± 13 m, P = 0.01), VO2max (increased by 2 ± 0.7 mL/kg/min, P = 0.02), time-to-VO2max (increased by 2.5 ± 0.6 min, P = 0.001), VO2 at anaerobic threshold (increased by 1.3 ± 0.5 mL/kg/min, P = 0.04), HR recovery (reduced by 68 ± 23% in slope, P = 0.01), and SF-36 subscales of Physical Functioning and Energy/Fatigue (increased by 70 ± 34% and 74 ± 34%, respectively, P < 0.05). No adverse events occurred, and right ventricular function and brain natriuretic peptide levels remained stable, suggesting safety of the intervention. This proof-of-concept study indicates that a simple walking regimen with arginine supplementation is a safe and efficacious intervention for clinically stable PAH patients, with gains in objective function and QoL measures. Further investigation in a randomized controlled trial is warranted.

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