Heart rate recovery in 1 minute after the 6-minute walk test predicts adverse outcomes in pulmonary arterial hypertension

Heart rate recovery in 1 minute (HRR1) after the end of the 6-minute walk test (6MWT) is a non-invasive method of determining autonomic dysfunction. This parameter remains largely unexplored in pulmonary arterial hypertension (PAH) registries. We aimed to define the cut-off value and accuracy for abnormal HRR1 after the 6MWT and to investigate the association between HRR1 and clinical worsening in patients with PAH. This composite outcome was defined as first occurrence of all-cause death OR hospitalization from any cause OR disease progression characterized by decreased ≥ 15% in six-minute walking distance from baseline AND start of new specific PAH treatment or persistent worsening of World Health Organization functional class (WHO-FC). We performed a prospective cohort study that included 102 consecutive patients with PAH confirmed by right heart catheterization that underwent an 6MWT upon the diagnosis, recruited from September 2004 to April 2020 and followed up until April 2021 or death. The median HRR1 was 18 beats (IQR: 10-22), 50 and 52 PAH patients with <18 beats and ≥18 beats, respectively. The best cut-off for HRR1 to discriminate clinical worsening was 17 beats, with area under the curve (AUC) of 0.704 (95%CI: 0.584-0.824). The internal validation model by bootstrap showed an AUC of 0.676 (95%CI: 0.566-0.786) and the most accurate value was obtained in the seventh year of follow-up (AUC = 0.711; 95%CI: 0.596-0.844). Patients with an HRR1 <18 beats at baseline had a median event-free time of 2.17 years (95%CI: 1.82 to 2.52) versus 4.75 years (95%CI: 1.43 to 8.07) from those with ≥18 beats. In conclusion, a HRR1 value of less than 18 beats may be a reliable indicator of poor prognosis in patients with PAH.