Diurnal and seasonal variation in six-minute walk distance in pulmonary hypertension: Implications for clinical monitoring

IntroductionThe American Thoracic Society (ATS) six-minute walk test (6MWT) guidelines recommend repeat testing at the same time of day to minimise intraday variability. Whether diurnal or seasonal factors affect the 6MWT in pulmonary hypertension (PH) is unclear. We investigated associations between six-minute walk distance (6MWD) and secondary 6MWT parameters with time of day and season using cross sectional and longitudinal analyses.MethodsThis single-centre retrospective study (2019-2025) included PH patients undergoing 6MWT as per ATS guidelines. Cross-sectional analyses compared morning (AM, 07:00-12:00) vs afternoon (PM, 12:01-18:00) and seasonal effects on 6MWD using adjusted linear models. Longitudinal effects were examined with adjusted linear mixed effects models.ResultsThe cross-sectional cohort included 1,665 patients (AM n=734, PM n=931). Estimated marginal mean (EMM) 6MWD was higher in the morning than afternoon (354m vs 339m; p=0.005), with no seasonal variation (Winter 338m, Spring 354m, Summer 345m, Autumn 343m; p=0.20). The longitudinal cohort included 554 patients. EMM 6MWD was similar between AM and PM (396m vs 400m; p=0.16) and across seasons (Winter 395m, Spring 395m, Summer 399m, Autumn 398m; p=0.43). Maximal heart rate (MHR) was higher in the afternoon (115 vs 113 bpm; p=0.002) and lower in Summer/Autumn (113 bpm) vs Winter (116 bpm) and Spring (115 bpm; p=0.017).Conclusion6MWD was stable across time of day and season, supporting greater flexibility in scheduling 6MWTs than suggested by guidelines. Small variations in MHR were associated with circadian and seasonal influences but did not affect 6MWD. Prospective studies are needed to confirm these findings.