{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:47:28Z","timestamp":1785757648907,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Cardiovasc. Dev. Dis.","JCDD"],"abstract":"<jats:p>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\u2014which is ultimately responsible for maintaining systemic cardiac output\u2014remains 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\u2019, 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 (\u2265median). 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\u2019 (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\u2019, p = 0.0199) and LV systolic function (LVEF, HR 0.969, 95% CI 0.940\u20130.998, p = 0.0305) were extracted as significant prognostic predictors. Most notably, in the stepwise multivariable model restricted to the \u201cIPF with high RVSP\u201d subgroup (N = 104), the prognostic significance of diastolic function (Average e\u2019) was lost (p = 0.4577), whereas LVEF (HR 0.965, 95% CI 0.936\u20130.995, p = 0.0229) emerged as the sole independent predictor of mortality. Conclusions: In the overall ILD-PH cohort, reduced LV diastolic function (Average e\u2019) 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.<\/jats:p>","DOI":"10.3390\/jcdd13080363","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:24:07Z","timestamp":1785752647000},"page":"363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Significance of Echocardiographic Parameters in Patients with Pulmonary Hypertension Associated with Interstitial Lung Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-0669","authenticated-orcid":false,"given":"Shingo","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Diagnostic Radiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Kodama","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideya","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-7773","authenticated-orcid":false,"given":"Ryo","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minori","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4535-653X","authenticated-orcid":false,"given":"Tae","family":"Iwasawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shungo","family":"Sawamura","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9911-5936","authenticated-orcid":false,"given":"Naofumi","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1723-1724","authenticated-orcid":false,"given":"Daisuke","family":"Utsunomiya","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Yokohama City University, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kanagawa Cardiovascular Respiratory Center, Yokohama 236-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1007\/s10067-026-08151-6","article-title":"The presence of anti-Ro52\/SSA antibodies may predict concomitant pulmonary hypertension and poorer survival in patients with connective tissue disease-associated interstitial lung disease","volume":"45","author":"Chang","year":"2026","journal-title":"Clin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Le\u00f3n-Rom\u00e1n, F., Pintado-Cort, B., Largaespada-P\u00e9rez, G., Khandji-Aslan, H.G., and Mu\u00f1iz-Gonz\u00e1lez, F. (2025). Case Report: Inhaled treprostinil: An alternative for the treatment of refractory exacerbation of interstitial lung disease. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1639593"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1007\/s12325-025-03129-3","article-title":"Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD): Back to the Future","volume":"42","author":"Bernardinello","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"38","author":"Humbert","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2401324","DOI":"10.1183\/13993003.01324-2024","article-title":"Definition, classification and diagnosis of pulmonary hypertension","volume":"64","author":"Kovacs","year":"2024","journal-title":"Eur. Respir. J."},{"key":"ref_6","first-page":"e89111","article-title":"Prevalence of Pulmonary Hypertension in Patients with Pulmonary Langerhans Cell Histiocytosis: A Systematic Review and Meta-Analysis","volume":"17","author":"Krishnan","year":"2025","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e70035","DOI":"10.1002\/pul2.70035","article-title":"Right Heart Catheterization Accurately Diagnoses Pulmonary Hypertension in Patients with Interstitial Lung Disease: Results From a Long-Term Cohort Study","volume":"15","author":"Escobedo","year":"2025","journal-title":"Pulm. Circ."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.15420\/ecr.2024.11","article-title":"Shifting Paradigms in the Management of Pulmonary Hypertension","volume":"19","author":"Pradhan","year":"2024","journal-title":"Eur. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.chest.2024.04.025","article-title":"Pulmonary Hypertension in Interstitial Lung Disease: A Systematic Review and Meta-Analysis","volume":"166","author":"Ang","year":"2024","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.healun.2021.03.004","article-title":"Pulmonary hypertension in fibrosing idiopathic interstitial pneumonia: Uncertainties, challenges and opportunities","volume":"40","author":"Girgis","year":"2021","journal-title":"J. Heart Lung Transplant. Off. Publ. Int. Soc. Heart Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1111\/imj.15887","article-title":"Clinical assessment for pulmonary hypertension in interstitial lung disease","volume":"53","author":"Chan","year":"2023","journal-title":"Intern. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"210220","DOI":"10.1183\/16000617.0220-2021","article-title":"Recent advances in the management of pulmonary hypertension with interstitial lung disease","volume":"31","author":"Waxman","year":"2022","journal-title":"Eur. Respir. Rev. Off. J. Eur. Respir. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15502","DOI":"10.1038\/s41598-021-94907-w","article-title":"Diagnostic and prognostic significance of serum angiopoietin-1 and -2 concentrations in patients with pulmonary hypertension","volume":"11","author":"Enomoto","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Santoro, C., Buonauro, A., Canora, A., Rea, G., Canonico, M.E., Esposito, R., Sanduzzi, A., Esposito, G., and Bocchino, M. (2022). Non-Invasive Assessment of Right Ventricle to Arterial Coupling for Prognosis Stratification of Fibrotic Interstitial Lung Diseases. J. Clin. Med., 11.","DOI":"10.3390\/jcm11206115"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.36740\/WLek202009109","article-title":"The Difficulties in the Diagnosis of Pulmonary Hypertension Associated with Chronic Lung Disease","volume":"73","author":"Tomaszewski","year":"2020","journal-title":"Wiad. Lek."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.echo.2018.06.004","article-title":"Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography","volume":"32","author":"Mitchell","year":"2019","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.59556\/japi.73.0855","article-title":"Spectrum of Clinical Manifestations in Patients of Scleroderma and Correlation between Cutaneous and Pulmonary Involvement","volume":"73","author":"Oak","year":"2025","journal-title":"J. Assoc. Physicians India"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/mr\/roae095","article-title":"Mortality and associated factors in patients with systemic sclerosis-associated pulmonary hypertension with and without interstitial lung disease: A long-term follow-up study","volume":"35","author":"Amikishiyev","year":"2025","journal-title":"Mod. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1007\/s10067-021-06016-8","article-title":"Clinical phenotypes, hemodynamic characteristics and prognosis of Chinese patients with systemic sclerosis-associated precapillary pulmonary hypertension: A retrospective study","volume":"41","author":"Yuan","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"O\u011fuz, M.S., Bing\u00f6l, Z., P\u0131ht\u0131l\u0131, A., Karaca \u00d6zer, P., Sar\u0131ta\u015f Arslan, M., K\u0131l\u0131\u00e7aslan, Z., Bilge, A.K., K\u0131yan, E., and Okumu\u015f, G. (2024). Oxygen saturation recovery after 6-minute walk test in patients with idiopathic pulmonary fibrosis. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03188-2"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s12574-021-00532-x","article-title":"Prognostic value of 6-min walk stress echocardiography in patients with interstitial lung disease","volume":"19","author":"Yasui","year":"2021","journal-title":"J. Echocardiogr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s10554-022-02541-y","article-title":"Incremental prognostic value of arterial elastance in mild-to-moderate idiopathic pulmonary fibrosis","volume":"38","author":"Sonaglioni","year":"2022","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jang, J.H., Jang, H.J., and Lee, J.H. (2024). A Case of Interstitial Lung Disease-Related Pulmonary Hypertension Successfully Treated with Inhaled Iloprost. Life, 14.","DOI":"10.3390\/life14091068"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S2213-2600(15)00543-3","article-title":"A global view of pulmonary hypertension","volume":"4","author":"Hoeper","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1136\/thorax-2023-220179","article-title":"Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease","volume":"79","author":"Sato","year":"2024","journal-title":"Thorax"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1161\/CIRCULATIONAHA.117.029254","article-title":"Prognostic Value of Follow-up Hemodynamics in Patients with Pulmonary Arterial Hypertension","volume":"137","author":"Weatherald","year":"2018","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ejhf.1029","article-title":"Right heart dysfunction and failure in heart failure with preserved ejection fraction: Mechanisms and clinical implications","volume":"20","author":"Gorter","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1801914","DOI":"10.1183\/13993003.01914-2018","article-title":"Pulmonary hypertension in chronic lung disease and\/or hypoxia","volume":"53","author":"Nathan","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.jacc.2018.12.076","article-title":"Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review","volume":"73","author":"Sanz","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s11739-021-02883-w","article-title":"Survival of patients with idiopathic pulmonary fibrosis and pulmonary hypertension under therapy with nintedanib or pirfenidone","volume":"17","author":"Lacedonia","year":"2022","journal-title":"Intern. Emerg. Med."},{"key":"ref_31","first-page":"1650","article-title":"Accuracy of Doppler echocardiography in the estimation of pulmonary artery pressure in patients with metabolic syndrome or chronic kidney disease","volume":"101","author":"Fisher","year":"2008","journal-title":"Am. J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1056\/NEJMoa2008470","article-title":"Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease","volume":"384","author":"Waxman","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_33","first-page":"110","article-title":"Inhaled Treprostinil for Pulmonary Hypertension Associated with Interstitial Lung Disease: Rapid clinical updates","volume":"205","author":"Nathan","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/resp.14378","article-title":"Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study","volume":"28","author":"Dawes","year":"2023","journal-title":"Respirology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jacc.2007.10.041","article-title":"Interventricular mechanical asynchrony in pulmonary arterial hypertension: Left-to-right delay in diastolic peak filling rate","volume":"51","author":"Marcus","year":"2008","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/8\/363\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:14:34Z","timestamp":1785755674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/8\/363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcdd13080363"],"URL":"https:\/\/doi.org\/10.3390\/jcdd13080363","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}