Response to "Noninvasive determinants of pulmonary hypertension (PH) in interstitial lung disease (ILD)" by Joseph et al.

We read with great interest the recently published paper “Noninvasive determinants of pulmonary hypertension (PH) in interstitial lung disease (ILD)” by Joseph et al.1 In this paper, the authors assessed gas exchange parameters obtained during submaximal exercise testing as a noninvasive measure to detect PH in ILD patients. Based on their results, they suggest utilizing a combination of estimated right ventricular systolic pressure (eRVSP) by echocardiogram, the ratio of the forced vital capacity (FVC) to diffusing capacity for carbon monoxide (DLCO), and GXCAP, a gas-exchanged derived estimate of pulmonary vascular capacitance, to predict concomitant PH in ILD patients. While we commend the authors on their excellent and novel work, we would raise the following questions in regard to their investigation. GXCAP assessed during submaximal exercise testing, while a novel measurement to detect PH in ILD patients, has been shown to have a similar predictive role in heart failure with preserved ejection fraction (HFpEF) patients.2 HFpEF patients were not specifically excluded from this present study since practically speaking, invasive hemodynamics alone (i.e., pulmonary artery wedge pressure less than 15 mmHg) is neither sensitive nor specific for ruling out HFpEF. As a result, could HFpEF had played a confounding role in the outcomes of the patients in the PH-ILD group? Perhaps incorporating other determinants of diastolic heart disease such as left atrium volume index and the ratio between early mitral inflow velocity and mitral annular early diastolic velocity on echocardiogram would have provided additional information. Likewise, in the prior study by the same authors, an optimal cut-off of 394 was utilized to signal an abnormal GXCAP but in the present study, a cut-off of 416 was used, signaling some degree of inconsistency with this novel variable.2 A closer look at the data and the methodology to apply decision tree analysis via CART to choose predictive variables for PH-ILD is interesting. Unfortunately, the reliability of the individual components used is suspect.3 As the authors point out, relying on eRVSP in ILD patients has several challenges. Moreover, ILD patients in frequently undergo echocardiogram as part of routine ILD monitoring. Therefore, utilizing variables that are commonly assessed in ILD patients to develop a tool for early detection in PH may be more practical.4, 5 On the other hand, FVC/DLCO ratio has previously been utilized in multi-component scoring tools to improve the overall accuracy of predicting PH in ILD patients and pulmonary function testing is routinely performed in this patient population.6 In conclusion, we commend Joseph et al. for excellent work in attempting to identify noninvasive determinants of PH in ILD patients. In particular, the utilization of exercise variables to determine the concomitant presence of PH is novel and unique. However, we would caution that the use of GXCAP, without a well-established abnormal cut-off point, and the potential confounder of HFpEF in this study requires further investigation and validation. We would also suggest that routine testing in ILD patients, such as pulmonary function tests and chest imaging, plays a more significant role in the early detection of PH rather than use of inconsistent variables such as an eRVSP by echocardiogram.4, 5 That said, we share in their overarching message and also emphasize and encourage the need to detect PH early in ILD patients so as to potentially treat these patients with inhaled pulmonary vasodilator therapy and/or refer for lung transplant evaluation. Raj Parikh: Conceptualization; data curation; investigation; methodology; validation; writing-original draft; writing-review and editing; guarantor. Harrison W. Farber: Conceptualization; investigation; methodology; validation; writing-original draft; writing-review and editing. The authors declare no conflict of interest. Informed consent from IRB was not reqired for this study. The data can be made available.