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

NCT06095466 | Recruiting

• 1 other identifier: INT/IEC/2023/SPL-963
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhotic Cardiomyopathy; Cirrhosis, Liver; Cardiac Disease

Outcome Measures

Primary Outcomes (1)

• Determine the prevalence of cirrhotic cardiomyopathy in critically ill patients with cirrhosis

  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.

  At Enrollment

Secondary Outcomes (3)

• Determine severity of cardiac dysfunction in critically ill patients with cirrhosis

  At Enrollment

• Determine the POCUS determinants of cardiac dysfunction in critically ill patients with cirrhosis

  At Enrollment

• Determine the cardiac histology changes in critically ill patients with cirrhosis

  At the time of demise

Study Arms (1)

Cirrhotic cardiomyopathy

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.

Device: Echocardiographic assessment; Diagnostic Test: Histopathology and Immunohistochemistry

Interventions

Echocardiographic assessment DEVICE

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.

Cirrhotic cardiomyopathy

Histopathology and Immunohistochemistry DIAGNOSTIC_TEST

In patients who do not survive, we will take a trucut core biopsy from the ventricular myocardium, using ultrasound guidance. Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, in this protocol, only those patients who consent to autopsy or those who consent to most mortem biopsy will be sampled for cardiac histology in CCM. Thus samples for histology and immunohistopathology will be available in only a few patients. For the immunohistochemistry study, the sections will be collected on the poly-L-lysine covered slides and dried in a thermostat, at 37°C, for 24 hours, for increasing the adherence of the biological material to the histological slide.

Cirrhotic cardiomyopathy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The target population for this study is all critically ill cirrhotic patients admitted to the Liver Intensive Care Unit of the Department of Hepatology, PGIMER Chandigarh

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Dr. Madhumita Premkumar

Sector-12, Chandigarh, 160012, India

RECRUITING

Related Publications (5)

• Premkumar M, Devurgowda D, Vyas T, Shasthry SM, Khumuckham JS, Goyal R, Thomas SS, Kumar G. Left Ventricular Diastolic Dysfunction is Associated with Renal Dysfunction, Poor Survival and Low Health Related Quality of Life in Cirrhosis. J Clin Exp Hepatol. 2019 May-Jun;9(3):324-333. doi: 10.1016/j.jceh.2018.08.008. Epub 2018 Aug 30.

  PMID: 31360025 BACKGROUND

• Premkumar M, Anand AC. Overview of Complications in Cirrhosis. J Clin Exp Hepatol. 2022 Jul-Aug;12(4):1150-1174. doi: 10.1016/j.jceh.2022.04.021. Epub 2022 May 14.

  PMID: 35814522 BACKGROUND

• Kaur H, Premkumar M. Diagnosis and Management of Cirrhotic Cardiomyopathy. J Clin Exp Hepatol. 2022 Jan-Feb;12(1):186-199. doi: 10.1016/j.jceh.2021.08.016. Epub 2021 Aug 21.

  PMID: 35068798 BACKGROUND

• 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.

  PMID: 31342529 BACKGROUND

• Wiese S, Voiosu A, Hove JD, Danielsen KV, Voiosu T, Gronbaek H, Moller HJ, Genovese F, Reese-Petersen AL, Mookerjee RP, Clemmesen JO, Gotze JP, Andersen O, Moller S, Bendtsen F. Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy. Aliment Pharmacol Ther. 2020 Jul;52(2):340-350. doi: 10.1111/apt.15812. Epub 2020 Jun 11.

  PMID: 32524673 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum Sample

MeSH Terms

Conditions

Liver Cirrhosis; Heart Diseases

Interventions

Immunohistochemistry

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Central Study Contacts

Madhumita Premkumar

CONTACT

01722754777; drmadhumitap@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 23, 2023
• Study Start: July 15, 2023
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: October 23, 2023

Record last verified: 2023-10

Locations

IN (1)