Impaired Gas Exchange During Submaximal Exercise and Clinical Worsening in PAH

Asturias, Spain, young woman training in gym on a treadmill, legs section
In patients with pulmonary arterial hypertension, is abnormal pulmonary gas exchange during submaximal exercise associated with greater risk of clinical worsening events?

Patients with pulmonary arterial hypertension (PAH) whose ventilatory and pulmonary gas exchange indices indicated a higher than normal disease severity during submaximal cardiopulmonary exercise testing had a higher risk of clinical worsening events such as increased medication dosage, hospitalization, or mortality. This was among the results of a study presented at the American Thoracic Society (ATS) 2022 Annual Meeting, held in San Francisco, CA, May 13 to 18.

Patients with PAH can be distinguished from healthy counterparts by the level of pulmonary gas exchange observed during submaximal exercise. The authors were interested in learning whether low levels of pulmonary gas exchange during physical activity correlated with worse outcomes in patients with PAH.

Researchers based at Mayo Clinic Florida in Jacksonville selected 65 patients with PAH confirmed by right-heart catheterization (RHC; mean age, 62 ± 12 years; 55% women) and put them through a standard 6-minute submaximal exercise test between January 2019 and January 2021. The investigators collected patient data on ventilation and pulmonary gas exchange, including oxygen uptake, partial pressure of end-tidal CO2, and ventilatory equivalent for CO2 (V̇E /V̇CO2). The researchers then used these measures to develop a disease severity stratification rubric which they termed the “submaximal exercise severity score” (SESS).  Within the SESS rubric, scores of 1 or less indicated normal to mild disease; 1.1 to 3.0 indicated mild to moderate disease; and scores greater than 3 indicated moderate to severe disease.

With respect to clinical worsening events, the researchers found 32 patients (49%) had a drug dosage escalation at a median follow-up of 6.0 months, 26 (40%) underwent hospitalization at a median follow-up of 8.5 months, and 10 (15%) expired at a median follow-up of 9.0 months.

The researchers then divided study participants into SESS disease severity groups and used Kaplan-Meier estimates and a Cox proportional hazards model to detect associations between SESS scores and clinical worsening events.

Findings indicated that clinical worsening events were forecasted by SESS scores between 1.1 and 3.0 (hazard ratio (HR) = 3.59; 95% CI, 1.46-8.84; P <.01) or higher than 3.0 (HR = 4.95; 95% CI, 1.79-13.69; P <.01), compared with scores of 1 or less. The investigators also found that participants who had been stratified into the 2 higher SESS severity-level groups — mild to moderate (SESS scores of 1.1 to 3) and moderate to severe (SESS scores above 3) — had roughly the same risk of experiencing clinical worsening events (P =.601).

Study authors concluded that there was an association between ventilatory and pulmonary gas exchange levels during submaximal exercise testing that indicated mild to severe disease — as measured by SESS scores of greater than 1 — and “higher risk of escalation in medication, hospitalization, or death in patients with RHC-confirmed PAH.”


Taylor BJ, Call JT, Saunders H, et al. Association between submaximal exercise gas exchange and clinical worsening events in patients with pulmonary arterial hypertension. Presented at: the American Thoracic Society (ATS) 2022 Annual Meeting; May 13-18, 2022; San Francisco, CA. Abstract 618.