Ventilatory Variability Is Increased at Rest in Pulmonary Arterial Hypertension

Ventilatory instability is associated with adverse outcomes in left heart failure, with periodic breathing during awake, rest, sleep and exercise (exercise oscillatory ventilation) associated with increased mortality. Increased peripheral and central chemoreflex sensitivities and impairment of cardiac output have been implicated as causative mechanisms of ventilatory instability in heart failure. As these factors are also present in pulmonary arterial hypertension (PAH), we tested the hypothesis that variability of breath-by-breath ventilation at rest would be increased in PAH compared with healthy controls. In fourteen patients with PAH (9 female, age 48.4±12.8 years, mean ± SD) and 14 healthy participants (9 female, age 49.4±14.2 years) breath-by-breath measurement of tidal volume and breathing frequency was undertaken with a pneumotachometer connected via a mouthpiece with nose-clip for 10 minutes while they rested awake and supine. Ventilatory (V̇E) variability was assessed using root mean square of successive differences (RMSSD), standard deviation (SD), average real variability (ARV, i.e., sum of absolute differences in successive observations), coeffcient of variation (CoV), as well as Poincaré analysis and compared between PAH and healthy controls (Student’s t-test). Correlations between measures of ventilatory variability and pulmonary hemodynamic characteristics, exercise capacity and function were assessed with Pearson’s correlation coeffcient. Resting V̇E was higher in PAH compared to healthy controls (14.3±1.1 and 12.1±0.5 L·min −1 respectively; p=0.009). Measures of variability for V̇E were increased in PAH compared to healthy controls. More specifically, RMSSD (3.59±1.36 vs. 2.48±0.87 L·min −1 , p=0.017), SD (2.92±1.14 vs. 1.98±0.53 L·min −1 , p=0.012), ARV (2.47±0.97 vs. 1.67±0.60 L·min −1 , p=0.016), Poincaré SD1 (short-term variability, p=0.020) and SD2 (long-term variability, p=0.028) were increased in PAH compared to healthy controls, respectively. No correlations were found between measures of ventilatory variability and pulmonary hemodynamics (mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac output), six-minute walk distance or WHO functional class. In summary, resting ventilatory variability is increased in PAH and not associated with haemodynamic factors and exercise capacity. Whether such raised ventilatory variability in PAH is related to increased chemoreflex sensitivity requires exploration. This study received funding support from the Greenlane Research and Educational Fund (21/01/4153), Health Research Council of New Zealand (19/687), and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.