UC Irvine

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 /VCO₂ and end-tidal carbon dioxide: ETCO₂ ) 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 /VCO₂ and lower rest ETCO₂ (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 /VCO₂  = 0.70* and ETCO₂  = 0.73*. Based on this, optimal thresholds of rest V_E /VCO₂  > 40 mm Hg and rest ETCO₂  < 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 /VCO₂  > 40 mm Hg and ETCO₂  < 30 mm Hg) identify PVD.