Clinical Significance of Echocardiographic Parameters in Patients with Pulmonary Hypertension Associated with Interstitial Lung Disease

Abstract

Background: Pulmonary hypertension (PH)-complicating interstitial lung disease (ILD) is a devastating condition that severely limits exercise capacity, diminishes quality of life (QOL), and ultimately determines survival. The pathophysiological assessment of ILD-PH has traditionally focused on right ventricular (RV) parameters reflecting RV pressure overload and dysfunction. However, under extreme RV pressure overload where blood supply to the left heart is severely restricted, the prognostic role of left ventricular (LV) function—which is ultimately responsible for maintaining systemic cardiac output—remains poorly understood. This study aimed to comprehensively evaluate the hemodynamics of ILD patients using non-invasive transthoracic echocardiography, to determine the prognostic importance of LV functional parameters, particularly left ventricular ejection fraction (LVEF). Methods: This single-center, retrospective, observational study included 415 ILD patients diagnosed and treated at the Kanagawa Cardiovascular Respiratory Center. All patients underwent transthoracic echocardiography at diagnosis, from which parameters such as estimated right ventricular systolic pressure (RVSP), tissue Doppler-derived Average e’, and LVEF were obtained. A multivariable Cox proportional hazards model was applied to evaluate the association between these echocardiographic parameters and all-cause mortality. To account for the prognostic impact of the underlying disease, we conducted a stratified analysis of idiopathic pulmonary fibrosis (IPF) and non-IPF cohorts. Furthermore, to evaluate LV function under the most severe hemodynamic compromise, a subgroup analysis was restricted to IPF patients with elevated RVSP (≥median). Results: During a median follow-up of 27.2 months, 75 (18.1%) of the 415 patients died. In the multivariable Cox analysis of the overall cohort, a decreased Average e’ (HR 0.861, p = 0.0038) emerged as a strong independent predictor of poor prognosis. Stratified analysis revealed that in the non-IPF group (n = 208, 15 events), none of the variables achieved statistical significance. Conversely, in the IPF group (N = 207, 60 events), both LV diastolic function (Average e’, p = 0.0199) and LV systolic function (LVEF, HR 0.969, 95% CI 0.940–0.998, p = 0.0305) were extracted as significant prognostic predictors. Most notably, in the stepwise multivariable model restricted to the “IPF with high RVSP” subgroup (N = 104), the prognostic significance of diastolic function (Average e’) was lost (p = 0.4577), whereas LVEF (HR 0.965, 95% CI 0.936–0.995, p = 0.0229) emerged as the sole independent predictor of mortality. Conclusions: In the overall ILD-PH cohort, reduced LV diastolic function (Average e’) is a strong independent predictor of mortality. While elevated RVSP and low BMI showed a trend toward worsening prognosis, they were not statistically significant in multivariable analysis. The prognostic contribution of LV function is primarily driven by the IPF patient group, which has an inherently poor prognosis. Furthermore, in the severe subgroup of IPF patients heavily burdened by right heart overload, LV pump function (LVEF) becomes an independent, critical determinant of ultimate survival. Therefore, routine measurement and careful monitoring of the universal parameter LVEF are of paramount importance for the risk stratification of high-risk patients under such complex hemodynamics.