Cirrhotic Cardiomyopathy Based on Point-of-care Echocardiography, Biomarkers and Histology

Recruiting

• Conditions: Cirrhotic Cardiomyopathy; Cirrhosis, Liver; Cardiac Disease
• Interventions: Device: Echocardiographic assessment; Diagnostic Test: Histopathology and Immunohistochemistry

• Registration Number: NCT06095466
• Lead Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Brief Summary

Cirrhotic cardiomyopathy is associated with increased risk of complications like hepatorenal syndrome, refractory ascites, impaired response to stressors including sepsis, bleeding or transplantation, poor health related quality of life and increased morbidity and mortality. 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.

Detailed Description

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.

In this project the investigators will screen critically ill patients with cirrhosis admitted to the intensive care unit for presence of cirrhotic cardiomyopathy and perform point-of-care echocardiography, electrocardiography, and cardiorenal biomarker tests for determination of outcomes in CCM. In patients who do not survive, the cardiac histology will be assessed by ultrasound guided myocardial biopsy to assess degree of inflammation and fibrosis in CCM.

Study Timeline

• Study Start: 2023-07-15
• Study First Submitted: 2023-09-19
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-18
• Last Update Submitted: 2023-10-18
• Study First Posted: 2023-10-23
• Last Update Posted: 2023-10-23
• Primary Completion: 2026-08-15
• Study Completion: 2026-10-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Patients with cirrhosis who have been diagnosed by clinical, biochemical, histological (when available) criteria plus ultrasound imaging will be included if they meet the following:

  • Age range of 18-65 years
  • Cirrhosis with critical illness admitted to the Liver Intensive Care Unit

Exclusion Criteria

• Age >65 years
• Chronic renal disease
• Pregnancy and peripartum cardiomyopathy
• Valvular heart disease
• Sick sinus syndrome/ Pacemaker
• 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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cirrhotic cardiomyopathy	Echocardiographic assessment	Cirrhotic cardiomyopathy, among a broad spectrum of cardiac complications in cirrhosis, is characterized by systolic and diastolic cardiac dysfunction and electrocardiographic changes. However, it is seen more in NASH related cirrhotic patients, who have an additional risk of developing cardiac complications. Cirrhosis contributes to a including cirrhotic cardiomyopathy owing to various pathological conditions interlinked at the cellular and molecular level. A hyperdynamic circulatory state caused due to excessive release of vasodilators in a pro-inflammatory condition of cirrhosis, along with negative-inotropic pathways contributes to the development of a compromised cardiac function. Electrocardiography, 2D echocardiography with tissue Doppler or speckle tracking are the routine diagnostic tests used to diagnose CCM.
Cirrhotic cardiomyopathy	Histopathology and Immunohistochemistry	Cirrhotic cardiomyopathy, among a broad spectrum of cardiac complications in cirrhosis, is characterized by systolic and diastolic cardiac dysfunction and electrocardiographic changes. However, it is seen more in NASH related cirrhotic patients, who have an additional risk of developing cardiac complications. Cirrhosis contributes to a including cirrhotic cardiomyopathy owing to various pathological conditions interlinked at the cellular and molecular level. A hyperdynamic circulatory state caused due to excessive release of vasodilators in a pro-inflammatory condition of cirrhosis, along with negative-inotropic pathways contributes to the development of a compromised cardiac function. Electrocardiography, 2D echocardiography with tissue Doppler or speckle tracking are the routine diagnostic tests used to diagnose CCM.

Primary Outcome Measures

Name	Time	Method
Determine the prevalence of cirrhotic cardiomyopathy in critically ill patients with cirrhosis	At Enrollment	CCM is independent of etiology, and all patients should be assessed for this under diagnosed complication of liver disease. The presence of metabolic syndrome, use of alcohol and cirrhosis can contribute synergistically as risk factors for clinically undiagnosed case of CCM. In a nutshell, the cirrhotic heart displays a variation of structure and size, atherosclerotic lesions, and myocardium hypertrophy with impaired functioning, with fibrosis and remodeling in late stages.; The prevalence of patients with CCM diagnosed as per the 2020 CCM criteria of the AASLD will be assessed.

Secondary Outcome Measures

Name	Time	Method
Determine the POCUS determinants of cardiac dysfunction in critically ill patients with cirrhosis	At Enrollment	POCUS variables like cardiac output, SVRI, right ventricular variables, pulmonary artery pressure will be recorded.
Determine the cardiac histology changes in critically ill patients with cirrhosis	At the time of demise	In patients who consent for autopsy or post mortem biopsy, cardiac, liver, renal, lung and splenic histological changes will be assessed.
Determine severity of cardiac dysfunction in critically ill patients with cirrhosis	At Enrollment	Grade of left ventricular diastolic dysfunction will be assessed. Systolic function including stroke volume, velocity time integral and cardiac index will be assessed.

Trial Locations

Locations (1)

Dr. Madhumita Premkumar; 🇮🇳 Sector-12, Chandigarh, India