The Role Of Ventilatory Efficiency In Exercise Intolerance Among Patients With Postural Orthostatic Tachycardia Syndrome

Postural orthostatic tachycardia syndrome (POTS) is characterized by profound exercise intolerance (EI), often accompanied by dyspnea on exertion. Poor ventilatory efficiency, high minute ventilation/carbon dioxide production slope (VE/VCO2), is generally ascribed to hyperventilation and contributes to dyspnea on exertion and poor quality of life. The relationship between VE/VCO2 and EI during cardiopulmonary exercise testing (CPET) in patients with POTS has not been examined. PURPOSE: To determine the relationship between VE/VCO2 and EI in POTS patients. METHODS: This retrospective analysis included 276 POTS patients (Age: 26 ± 7 yrs; body mass index [BMI]: 24 ± 5 kg/m2) diagnosed by tilt-table test who underwent CPET between 2019-2023 at Mayo Clinic, Rochester. Measures included peak oxygen consumption (VO2peak), VCO2, VE, tidal volume (VT), respiratory rate (RR), and end-tidal partial pressure of carbon dioxide (PETCO2). Patients were grouped by VE/VCO2 slope of >30 (HIGH: n = 65) or < 30 (LOW: n = 211). Predicted peak values were calculated and independent t-tests were used to compare between-group differences. Data reported as mean ± SD. RESULTS: For the cohort, VO2peak was lower than predicted (1.7 ± 0.6 vs 2.5 ± 0.8 L/min) and VE/VCO2 slope was higher than predicted (28 ± 5 vs 24 ± 1) (both p < 0.05). There were no differences between HIGH and LOW for age (25 ± 7 vs 27 ± 7 yrs) or BMI (23 ± 5 vs 24 ± 5 kg/m2) respectively. HIGH demonstrated lower VO2peak (1.56 ± 0.4 vs 1.78 ± 0.6 L/min, respectively, p < 0.05). With this, HIGH had higher VE (66 ± 18 vs 60 ± 22 L) and RR (40 ± 8 vs 33 ± 7 bpm), with lower VCO2 (1.8 ± 0.5 vs 2.0 L/min) and PETCO2 (32 ± 3 vs 39 ± 4 mmHg), respectively (p < 0.05 for all). VT (1.6 ± 0.5 vs 1.7 ± 0.5 L) was not different between groups. VE/VCO2 slope correlated negatively with VO2peak (r = -0.41, p < 0.01) in HIGH. CONCLUSIONS: These data suggest POTS patients with poor ventilatory efficiency (high VE/VCO2 slope) have greater EI. Patients with higher slope have higher VE driven by higher RR with subsequent lower PETCO2. Poor ventilatory efficiency may contribute to EI and impact cardiopulmonary performance in POTS patients. Additional research is needed to fully elucidate the physiologic mechanisms contributing to ventilatory inefficiency and EI in POTS.