Point-of-Care Echocardiography to Assess Impact of Dynamic Cardiac Function, Renal and Cardiac Biomarkers in Cirrhosis With Refractory Ascites

Point-of-care echocardiography (POC-Echo) is used to determine left ventricular systolic and diastolic dysfunction (LVDD), inferior vena cava (IVC) dynamics and volume status in cirrhosis and Acute-on-chronic liver failure ACLF accurately.

We will assess IVC dynamics, LV systolic function [LV ejection fraction (EF) & cardiac output (CO)], and diastolic dysfunction (E/e', e' and E/A ratio) and urinary biomarkers (cystatin C and NGAL) in patients with cirrhosis and Refractory Ascites.

Study Overview

• Status: Recruiting
• Conditions: Acute-On-Chronic Liver Failure; Ascites; Acute Kidney Injury; Cirrhosis, Liver; Refractory Ascites
• Intervention / Treatment: Diagnostic test: Echocardiographic assessment

Detailed Description

The decrease in systemic vascular resistance (SVR) and redistribution of blood volume with reduced intravascular volume compartment and third space fluid losses. Systemic vasodilatation is compensated by an increase in cardiac output (CO) in the initial stages of compensated cirrhosis. However, as the stage of liver cirrhosis progresses to decompensation, more prominent arterial vasodilatation and reduced SVR leads to a fall in CO. Thus, the cardiac homeostat is reset in a cirrhotic hyperdynamic circulation, wherein an increased heart rate, and therefore, increased cardiac output will no longer be able to compensate for the reduced mean arterial pressure (MAP), and decreased blood volumes in central venous territories.18 Consequent activation of vasoconstrictor systems including renin-angiotensin-aldosterone, vasopressin and the sympathetic nervous system comes into play to maintain the intravascular blood volume and pressure. These compensatory pathways cause an increase in sodium and water retention resulting in refractory ascites and hepatorenal syndrome (HRS). In critically ill patients with cirrhosis, the limited cardiac reserve is further stressed, CCM and heart failure may be diagnosed for the first time when the patient develops sepsis or septic shock.

Point-of-care echocardiography (POC-Echo) is used to determine left ventricular systolic and diastolic dysfunction (LVDD), inferior vena cava (IVC) dynamics and volume status in cirrhosis accurately. We will assess IVC dynamics, LV systolic function [LV ejection fraction (EF) & cardiac output (CO)], and diastolic dysfunction (E/e', e' and E/A ratio) in patients with cirrhosis ACLF and refractory ascites

Definition of CCM is as per updated CCMC criteria of 2020.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Madhumita Premkumar; Phone Number: 01722754777; Email: drmadhumitap@gmail.com

Study Locations

• India
  • Delhi
    • Chandigarh, Delhi, India, 160012
      • Recruiting
      • PGIMER
      • Contact: Madhumita Premkumar; Phone Number: 01722754777; Email: drmadhumitap@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cirrhosis of any etiology, aged between 18-65 years, with Refractory Ascites definition as per International Ascites club.

1. Diuretic-resistant ascites
2. Diuretic-intractable ascites

Description

Inclusion Criteria:

• Cirrhosis of any Etiology
• Patient with Refractory Ascites

Exclusion Criteria:

• Hepatocellular carcinoma
• Patients with active variceal bleeding
• HIV or severe immunocompromised state
• Chronic kidney disease (CKD) on renal replacement therapy (RRT),
• Previous transjugular intra hepatic portosystemic shunt (TIPS)
• Porto-pulmonary hypertension,
• Coronary artery disease
• Congenital or valvular heart disease
• Prosthetic cardiac valves

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cirrhosis with Refractory Ascites	Diagnostic test: Echocardiographic assessment; POC-Echocardiography to assess dynamic changes in cardiac output to assess therapeutic responses with albumin, midodrine, diuretics and domiciliary albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2. The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation. Cardiac output(CO), Stroke volume (SV), Heart rate (HR) CO = [SV * HR]/ 1000	Day 0
Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2. The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation. Cardiac output(CO), Stroke volume (SV), Heart rate (HR) CO = [SV * HR]/ 1000	Day 1
Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2. The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation. Cardiac output(CO), Stroke volume (SV), Heart rate (HR) CO = [SV * HR]/ 1000	Day 2
Cardiac output measurement by echocardiography after albumin	Echocardiographic assessment of cardiac output in L/min will be recorded at least 3 time points, day 0, day 1 and day 2. The cardiac output at 3 days after enrollment and albumin therapy will also be documented. The Doppler velocity time integral (VTI) method in estimating stroke volume and cardiac output correlates well with results of concurrent thermodilution cardiac output determinations in patients without significant left-sided valvular regurgitation. Cardiac output(CO), Stroke volume (SV), Heart rate (HR) CO = [SV * HR]/ 1000	Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IVC size and collapsibility changes after 20% albumin	IVC maximum and Minimum diameter and collapsibility index determined by percentage change in IVC diameter will be recorded.	Day 0
IVC size and collapsibility changes after 20% albumin	IVC maximum and Minimum diameter and collapsibility index determined by percentage change in IVC diameter will be recorded.	Day 1
IVC size and collapsibility changes after 20% albumin	IVC maximum and Minimum diameter and collapsibility index determined by percentage change in IVC diameter will be recorded.	Day 2
Lung Ultrasound score change after 20% Albumin		Day 0
Lung Ultrasound score change after 20% Albumin		Day 1
Lung Ultrasound score change after 20% Albumin		Day 2
Change in Cystatin C and Neutrophil gelatinase associated lipocalin (NGAL) level		day 0
Change in NT Pro brain natriuretic peptide (BNP) level		day 0
Change in plasma renin activity level		day 0
Change in Galectin-3 level		day 0

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Cardenas A, Arroyo V. Refractory ascites. Dig Dis. 2005;23(1):30-8. doi: 10.1159/000084723.
• Adebayo D, Neong SF, Wong F. Refractory Ascites in Liver Cirrhosis. Am J Gastroenterol. 2019 Jan;114(1):40-47. doi: 10.1038/s41395-018-0185-6.
• Larrue H, Vinel JP, Bureau C. Management of Severe and Refractory Ascites. Clin Liver Dis. 2021 May;25(2):431-440. doi: 10.1016/j.cld.2021.01.010. Epub 2021 Mar 11.
• Salerno F, Guevara M, Bernardi M, Moreau R, Wong F, Angeli P, Garcia-Tsao G, Lee SS. Refractory ascites: pathogenesis, definition and therapy of a severe complication in patients with cirrhosis. Liver Int. 2010 Aug;30(7):937-47. doi: 10.1111/j.1478-3231.2010.02272.x. Epub 2010 May 21. Erratum In: Liver Int. 2010 Sep;30(8):1244.
• Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, Watt KD, Lee SS; Cirrhotic Cardiomyopathy Consortium. Redefining Cirrhotic Cardiomyopathy for the Modern Era. Hepatology. 2020 Jan;71(1):334-345. doi: 10.1002/hep.30875. Epub 2019 Oct 11. Erratum In: Hepatology. 2020 Sep;72(3):1161.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2022
• Primary Completion (Estimated): November 15, 2023
• Study Completion (Estimated): July 15, 2024

Study Registration Dates

• First Submitted: December 6, 2022
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Ascites; Acute kidney injury; Cirrhotic Cardiomyopathy
• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Pathologic Processes; Kidney Diseases; Urologic Diseases; Liver Diseases; Liver Failure, Acute; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; End Stage Liver Disease; Fibrosis; Liver Failure; Acute-On-Chronic Liver Failure; Liver Cirrhosis; Ascites; Acute Kidney Injury
• Other Study ID Numbers: NK-2020-2141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No