Noninvasive determinants of pulmonary hypertension in interstitial lung disease

Abstract

Pulmonary hypertension (PH) in interstitial lung disease (ILD) is associated with increased mortality and impaired exertional capacity. Right heart catheterization is the diagnostic standard for PH but is invasive and not readily available. Noninvasive physiologic evaluation may predict PH in ILD. Forty‐four patients with PH and ILD (PH‐ILD) were compared with 22 with ILD alone (non‐PH ILD). Six‐min walk distance (6MWD, 223 ± 131 vs. 331 ± 125 m, p = 0.02) and diffusing capacity for carbon monoxide (DLCO, 33 ± 14% vs. 55 ± 21%, p < 0.001) were lower in patients with PH‐ILD. PH‐ILD patients exhibited a lower gas‐exchange derived pulmonary vascular capacitance (GX CAP , 251 ± 132 vs. 465 ± 282 mL × mmHg, p < 0.0001) and extrapolated maximum oxygen uptake (VO 2max ) (56 ± 32% vs. 84 ± 37%, p = 0.003). Multivariate analysis was performed to determine predictors of VO 2 max . GX CAP was the only variable that predicted extrapolated VO 2 max among PH‐ILD and non‐PH ILD patients. Receiver operating characteristic curve analysis assessed the ability of individual noninvasive variables to distinguish between PH‐ILD and non‐PH ILD patients. GX CAP (area under the curve [AUC] 0.85 ± 0.04, p < 0.0001) and delta ETCO 2 (AUC 0.84 ± 0.04, p < 0.0001) were the strongest predictors of PH‐ILD. A CART analysis selected GX CAP , estimated right ventricular systolic pressure (eRVSP) by echocardiogram, and FVC/DLCO ratio as predictive variables for PH‐ILD. With this analysis, the AUC improved to 0.94 (sensitivity of 0.86 and sensitivity of 0.93). Patients with a GX CAP ≤ 416 mL × mmHg had an 82% probability of PH‐ILD. Patients with GX CAP ≤ 416 mL × mmHg and high FVC/DLCO ratio >1.7 had an 80% probability of PH‐ILD. Patients with GX CAP ≤ 416 mL × mmHg and an elevated eRVSP by echocardiogram >43 mmHg had 100% probability of PH‐ILD. The incorporation of GX CAP with either eRVSP or FVC/DLCO ratio distinguishes between PH‐ILD and non‐PH‐ILD with high probability and may therefore assist in determining the need to proceed with a diagnostic right heart catheterization and potential initiation of pulmonary arterial hypertension‐directed therapy in PH‐ILD patients.

The PH‐ILD Detection tool: External validation and use in patients with ILD

“…However, as noted above, further refinement of the tool will likely be warranted. Similar to the REVEAL risk assessment tools, the PH‐ILD Detection tool will continue to be re‐evaluated and its individual metrics constantly refined in an effort to create an evolving early detection method that can adjust as more data become available, potentially even including novel gas‐exchange parameters obtained during submaximal exercise testing 54–56 …”

Cognitive impairment in pulmonary arterial hypertension

“…The sub-maximum CPET involves subjects exercising by going up and down a step for 3 min while wearing a mouthpiece connected to a portable metabolic cart and a continuous gas exchange analyzer; a full protocol has been published previously. 6,7 Subjects were assessed for cognitive impairment using the Self-Administered Gerocognitive Exam (SAGE), a screening tool that tests multiple cognitive domains and has been used to detect cognitive impairment in nongeriatric populations with systemic disease. 8 A score of <17 on the SAGE is consistent with cognitive impairment.…”

“…Sub‐maximum derived exercise variables have been shown to confer prognostic significance in pulmonary hypertension 5 and unlike conventional CPET, a maximum exercise effort is not required, making it an attractive option for patients with cardiopulmonary or musculoskeletal disorders and elderly patients who often are unable to undergo maximum exercise testing. The sub‐maximum CPET involves subjects exercising by going up and down a step for 3 min while wearing a mouthpiece connected to a portable metabolic cart and a continuous gas exchange analyzer; a full protocol has been published previously 6,7 …”

Response to letter to the editor “noninvasive determinants of pulmonary hypertension in interstitial lung disease”

“…We thank Parikh et al for their interest in our published work describing noninvasive determinants of pulmonary hypertension in interstitial lung disease (PH‐ILD). 1 Using submaximum exercise testing in a cohort of patients with known PH‐ILD, we describe gas exchange derangements such as delta end‐tidal carbon dioxide (ETCO 2 ) and gas‐exchange derived pulmonary vascular capacitance (GX CAP ) as predictive of PH‐ILD. Furthermore, we use Classification and Regression Tree (CART) analysis to show that the combination of GX CAP with either estimated right ventricular systolic pressure (eRVSP) or FVC/DLCO ratio distinguishes between PH‐ILD and non‐PH‐ILD with high probability.…”