Distinguishing exercise intolerance in early-stage pulmonary hypertension with invasive exercise hemodynamics: Rest V E /VCO 2 and ETCO 2 identify pulmonary vascular disease.

Background: Among subjects with exercise intolerance and suspected early-stage pulmonary hypertension (PH), early identification of pulmonary vascular disease (PVD) with noninvasive methods is essential for prompt PH management.
Hypothesis: Rest gas exchange parameters (minute ventilation to carbon dioxide production ratio: V _E /VCO ₂ and end-tidal carbon dioxide: ETCO ₂ ) can identify PVD in early-stage PH.
Methods: We conducted a retrospective review of 55 subjects with early-stage PH (per echocardiogram), undergoing invasive exercise hemodynamics with cardiopulmonary exercise test to distinguish exercise intolerance mechanisms. Based on the rest and exercise hemodynamics, three distinct phenotypes were defined: (1) PVD, (2) pulmonary venous hypertension, and (3) noncardiac dyspnea (no rest or exercise PH). For all tests, *p < .05 was considered statistically significant.
Results: The mean age was 63.3 ± 13.4 years (53% female). In the overall cohort, higher rest V _E /VCO ₂ and lower rest ETCO ₂ (mm Hg) correlated with high rest and exercise pulmonary vascular resistance (PVR) (r ~ 0.5-0.6*). On receiver-operating characteristic analysis to predict PVD (vs. non-PVD) subjects with noninvasive metrics, area under the curve for pulmonary artery systolic pressure (echocardiogram) = 0.53, rest V _E /VCO ₂  = 0.70* and ETCO ₂  = 0.73*. Based on this, optimal thresholds of rest V _E /VCO ₂  > 40 mm Hg and rest ETCO ₂  < 30 mm Hg were applied to the overall cohort. Subjects with both abnormal gas exchange parameters (n = 12, vs. both normal parameters, n = 19) had an exercise PVR 5.2 ± 2.6* (vs. 1.9 ± 1.2), mPAP/CO slope with exercise 10.2 ± 6.0* (vs. 2.9 ± 2.0), and none included subjects from the noncardiac dyspnea group.
Conclusions: In a broad cohort of subjects with suspected early-stage PH, referred for invasive exercise testing to distinguish mechanisms of exercise intolerance, rest gas exchange parameters (V _E /VCO ₂  > 40 mm Hg and ETCO ₂  < 30 mm Hg) identify PVD.
(© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)