Cardiac Dysfunction in Patients with Fatty Liver Disease

Cirrhotic Cardiomyopathy and Cardiac Dysfunction in Patients with Metabolic Dysfunction Associated Steatotic Liver Disease

Cirrhotic cardiomyopathy is seen as a blunted contractile responsiveness to stress, and/or altered diastolic relaxation with electrophysiological abnormalities, in absence of known cardiac disease. Left ventricular diastolic dysfunction (LVDD) is associated with risk of hepatorenal syndrome (HRS) , septic shock. , heart failure in the perioperative period following liver transplantation, and after trans-jugular intrahepatic portosystemic shunt (TIPS) insertion . The echocardiographic E/e' ratio is a predictor of survival in LVDD, with multiple studies, including prospective data from our Centre. The inability of the heart to cope with stress or sepsis induced circulatory failure is a key concept of the increased mortality risk due to LVDD. In view of the metabolic syndrome and diabetes epidemic and an increasing number of patients being diagnosed with non-alcoholic fatty liver disease, there is increased risk of developing cardiac dysfunction due to multiple comorbidities including coronary artery disease, hypertensive heart disease, cirrhotic cardiomyopathy, which are contributors to overall cardiovascular risk of mortality.

Study Overview

• Status: Recruiting
• Conditions: Fatty Liver; NAFLD; Cardiac Disease; MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease
• Intervention / Treatment: Diagnostic test: Echocardiographic assessment

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are obesity-related conditions with high cardiovascular mortality. Many new studies have linked NAFLD to changes in myocardial energy metabolism, and to echocardiographic measurements of cardiac dysfunction especially heart failure with preserved ejection fraction. Cardiac dysfunction in NAFLD is related to the release of inflammatory cytokines among those with steatohepatitis (NASH). However composite models looking at coronary artery disease, systolic and diastolic heart failure and outcomes in patients with NAFLD are limited, and the few preliminary analyses of this relationship using histologically-defined NASH or lean NAFLD remain unclear.

In this project the investigators will screen patients with a diagnosis of 'non-alcoholic fatty liver disease' for presence of coronary artery disease, arrhythmias, cirrhotic cardiomyopathy and develop a model for cardiac dysfunction in such patients.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

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

Study Locations

• India
  • Chandigarh, India, 160012
    • Recruiting
    • Dr. Madhumita Premkumar
    • Contact: Dr. Madhumita Premkumar, MD; Phone Number: +9101722754777; Email: drmadhumitap@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The target population for this study is all patients with a diagnosis of metabolic dysfunction associated steatotic liver disease seen in the outpatient and inpatient services of the Department of Hepatology, PGIMER Chandigarh.

Description

Inclusion Criteria:

• Age range of 18-65 years
• metabolic dysfunction associated steatotic liver disease as diagnosed either by histology or clinical, laboratory, non invasive tests, USG findings and vibration controlled transient elastography (VCTE).

Exclusion Criteria:

• Age >65 years
• Chronic renal disease
• Pregnancy and peripartum cardiomyopathy
• Hypertension
• Valvular heart disease
• Sick sinus syndrome/ Pacemaker
• Cardiac rhythm disorder
• Hypothyroidism
• Hyperthyroidism
• Portal vein thrombosis
• Transjugular intrahepatic porto systemic shunt (TIPS) insertion
• Hepatocellular carcinoma
• Anemia Hb < 8gm/dl in females, and < 9 gm/dl in males at the time of assessment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

MASLD; Non invasive tests like APRI, FIB-4, , FAST scan and VCTE in the form of Fibroscan will be done and recorded. Liver biopsy would be done as per the clinical indication. Diagnosis of NAFLD will be based on history, physical examination, laboratory investigations, upper gastrointestinal endoscopy, imaging studies (ultrasonography and Doppler of spleno portal venous axis, VCTE) and liver biopsy where available.

Diagnostic test: Echocardiographic assessment; M mode, cross sectional and pulsed wave Doppler Echocardiographic examinations will be performed using a with a 2.5 MHz wide angle phased array transducer. Patients will be laid in left lateral position and examined in standard parasternal long and short axis and apical views. Short axis recordings will be performed at the level of the papillary muscles. M mode tracings will be recorded at the level of the papillary muscles and the aortic valves, with 2 -D guidance. LV wall thickness and cavity diameters will be measured by M mode, through the largest diameter of the ventricle, if possible, both in diastole and systole. Using the cross-sectional images as a guide, the M mode tracing of the left ventricle will obtained to calculate measurements according to the recommendations of American Society of Echocardiography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the prevalence of cardiac dysfunction in patients with non-alcoholic fatty liver disease/ metabolic dysfunction associated steatotic liver disease	Prevalence of CCM in the MASLD cohort	At Enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of myocardial abnormalities in CCM dysfunction	Use of cardiac MRI or CT	At Enrolment
Presence of perfusion abnormalities in CCM dysfunction	Use of LV scintigraphy	At Enrolment
All cause mortality in metabolic dysfunction associated steatotic liver disease	All cause mortality will be recorded	12 months after enrolment
Cardiac event related mortality in MASLD	Cardiovascular events like incidence of arrhythmia, symptomatic heart failure related deaths will be recorded.	12 months after enrolment
To determine the severity of cardiac dysfunction in patients with metabolic dysfunction associated steatotic liver disease	Prevalence of CCM in the MASLD cohort, and grade of LV diastolic and systolic dysfunction	At Enrolment

Collaborators and Investigators

• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Publications and helpful links

General Publications

• Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Feb 22.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2023
• Primary Completion (Estimated): August 15, 2027
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: September 19, 2023
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Cirrhotic Cardiomyopathy; MASLD; Heart failure in Cirrhosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Digestive System Diseases; Heart Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: INT/IEC/2023/SPL-902; IEC/2024/1523 dt 3.12.2024 (Other Identifier: Postgraduate Institute of Medical Education and Research)

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
• product manufactured in and exported from the U.S.: No