Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Cardiopulmonary changes and its association with clinical features in noncirrhotic portal hypertension
Harish Gopalakrishna, My-Le Nguyen, Maria Mironova, Gracia M Viana Rodriguez, Rownock Afruza, Moumita Chakraborty, Matthew G Menkart, Jenna L Oringher, Shani Scott, Gayatri B Nair, David E Kleiner, Christopher Koh, Michael Fallon, Vandana Sachdev, Theo Heller
Harish Gopalakrishna, Maria Mironova, Gracia M Viana Rodriguez, Shani Scott, Christopher Koh, Theo Heller, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
My-Le Nguyen, Vandana Sachdev, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States
Rownock Afruza, Moumita Chakraborty, Matthew G Menkart, Jenna L Oringher, Theo Heller, Liver Diseases Branch, Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States
Gayatri B Nair, Department of Pulmonary and Sleep Medicine, Medstar Georgetown University Hospital, Washington DC, WA 20007, United States
David E Kleiner, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States
Michael Fallon, Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, AZ 85040, United States
Co-corresponding authors: Harish Gopalakrishna and Theo Heller.
Author contributions: Gopalakrishna H and Heller T conceptualized and designed the study; Gopalakrishna H, Nguyen ML, Mironova M and Heller T performed data analysis; Gopalakrishna H, Nguyen ML, Mironova M, Viana Rodriguez GM, Afruza R, Chakraborty M, Menkart MG, Oringher JL, Scott S, Nair GB, Kleiner DE, and Sachdev V performed data acquisition and interpretation; Gopalakrishna H, Nguyen ML, Mironova M, Koh C, Fallon M, Sachdev V, and Heller T performed data interpretation; Gopalakrishna H and Heller T wrote the manuscript. All authors have read, revised and approved the final manuscript. Both co-corresponding authors have made equally important contributions to the conception, design, execution, and interpretation of the study. Throughout the project, we shared key responsibilities, including data analysis, manuscript writing, and coordinating with co-authors. We both have taken active roles in responding to reviewer comments and revising the manuscript. Given these roles, we believe that recognizing both as co-corresponding authors ensures accurate representation of our contributions.
Supported by Division of Intramural Research Program at National Institute of Diabetes and Digestive and Kidney Diseases, No. 1ZIADK075008.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the National Institutes of Health (NCT02417740).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None of the authors have any conflict of interest to disclose.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at
theoh@intra.niddk.nih.gov.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Harish Gopalakrishna, MD, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive BLDG, Bethesda, MD 20892, United States.
hkgp44@gmail.com
Received: May 6, 2025
Revised: June 5, 2025
Accepted: July 16, 2025
Published online: August 14, 2025
Processing time: 93 Days and 15.1 Hours
BACKGROUND
Cardiopulmonary changes in noncirrhotic portal hypertension (NCPH) are poorly understood.
AIM
To investigate cardiopulmonary changes using transthoracic echocardiography (TTE) in NCPH and their correlation with clinical features.
METHODS
Prospective cohort including 10 preclinical NCPH [without portal hypertension (PH)] and 32 NCPH subjects who underwent TTE with agitated saline injection and comprehensive clinical evaluation were assessed. PH was defined by presence of either varices, ascites or portosystemic shunting. Intrapulmonary vascular dilatation (IPVD) is defined as appearance of microbubbles in the left atrium after three heartbeats. Right ventricular systolic pressure (RVSP) > 38 mmHg was used to identify possible porto-pulmonary hypertension. Cardiomyopathy is defined using cirrhotic cardiomyopathy consortium criteria.
RESULTS
Among 42 subjects, 17 (40%) had IPVD, 4 (9.5%) had RVSP > 38 mmHg, and 6 (14%) had cardiomyopathy. Aspartate aminotransferase to alanine aminotransferase (AST/ALT) (1.3 vs 1, P = 0.04) and liver stiffness measurement (LSM) (12.4 kPa vs 7.1 kPa, P = 0.03) were higher in those with IPVD. Presence of either LSM > 10 or AST/ALT > 1.2 aided in identifying subjects with IPVD-sensitivity, specificity, and accuracy of 76%. RVSP correlated with oxygen saturation (r = -0.33), and free right hepatic vein pressure (r = 0.43). Those with PH had higher left atrial volume (LAV) (62 mL vs 48 mL, P < 0.01), and LAV index (LAVI) (35 m2vs 23 m2, P < 0.01) compared to those without PH. Total bile acids, especially primary bile acids positively correlated with LAV (r = 0.36), and LAVI (r = 0.41).
CONCLUSION
Similar to cirrhotic patients, cardiopulmonary changes are prevalent in NCPH, especially among those with PH. In NCPH, cardiopulmonary changes occur despite preserved synthetic function, suggesting the NCPH model's value in understanding cardiopulmonary dysfunction in liver disease.
Core Tip: In this study, cardiopulmonary changes in noncirrhotic portal hypertension (NCPH) were investigated using echocardiography and its association with clinical features was explored. Cardiopulmonary changes are prevalent in NCPH patients as in those with cirrhosis. Unlike cirrhosis, cardiopulmonary complications occur despite preserved synthetic function of liver. Liver stiffness measurement and aspartate aminotransferase to alanine aminotransferase ratio help identify patients at risk of hepatopulmonary syndrome.
