Hyperventilation in Patients with Postural Orthostatic Tachycardia Syndrome (POTS): Effects of Tidal Volume versus Hypocapnia on Heart Rate

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic form of orthostatic intolerance that significantly impacts the quality of life and day-to-day functioning of patients. POTS has an estimated prevalence of about 1%, predominantly affecting females of child-bearing age. POTS is characterized by an upright increase in heart rate (HR) of ≥30 bpm, without a drop in blood pressure. POTS is associated with chronic (≥ 3 months) upright symptoms including light-headedness, blurred vision, and cognitive dysfunction. A large proportion of POTS patients also experience hyperventilation when upright. Hyperventilation reduces arterial carbon dioxide (CO 2 ; hypocapnia) and exacerbates tachycardia in POTS. Whether the HR response is due to increased tidal volume (V T ) per se or the resulting hypocapnia is unclear. Investigating the independent effects of increased V T versus hypocapnia on HR might identify possible therapeutic targets to reduce HR in patients with POTS. Objective: We aimed to characterize the separate effects of hypocapnia and V T on HR in POTS patients. Hypothesis: We hypothesize that hypocapnia and V T will independently increase HR, with hypocapnia causing the greatest increase in HR in patients with POTS. Methods: Twenty female POTS patients (32±10 years) completed supine normocapnic and hypocapnic breathing tests. To assess the effects of hypocapnia on HR, we compared hypocapnic-hyperventilation versus normocapnic-hyperventilation with constant V T . To assess the effects of V T on HR, we compared increased V T breathing versus normal breathing with constant end-tidal CO 2 (ETCO 2 ). Breath-by-breath respiratory (V T , ETCO 2 ) and beat-to-beat hemodynamic parameters (stroke volume [SV], HR) were continuously measured. Data were analyzed with paired t-tests, and are reported as mean ± SD. Results: ETCO 2 was lower ( p<0.001) with similar V T during hypocapnia compared to normocapnia. Hypocapnia reduced SV (63.3±11.8 mL vs. 72.4±12.3 mL; p<0.001), and increased HR (99±13 bpm vs. 81±9 bpm; p<0.001). Compared to normal breathing, increased V T ( p<0.001) with constant ETCO 2 led to a smaller reduction in SV (72.4±12.3 mL vs. 76.0±14.3 mL; p=0.04), and increase in HR (81±9 bpm vs. 75±9 bpm; p<0.001). Conclusion: Our results suggest that hypocapnia and increased V T independently reduce SV and increase HR in POTS patients. The increase in HR was greater during hypocapnia (+18 bpm) compared to increased V T (+6 bpm). Reducing hypocapnia presents an attractive therapeutic target. Disclosures: This work was supported by Standing up to POTS. 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.