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

Cardiac Disease Clinical Trial

Official title:

Diagnosis and Pathogenetic Mechanisms in Cirrhotic Cardiomyopathy Based on Point-of-care Echocardiography, Biomarkers and Histology

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06095466
• Other study ID #: INT/IEC/2023/SPL-963
• Status: Recruiting
• Start date: July 15, 2023
• Est. completion date: October 15, 2026

Study information

• Verified date: October 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Madhumita Premkumar
• Phone: 01722754777
• Email: drmadhumitap[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 15, 2026
• Est. primary completion date: August 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Disease
• Cardiomyopathies
• Cirrhosis, Liver
• Cirrhotic Cardiomyopathy
• Heart Diseases
• Liver Cirrhosis

Intervention

Device:
• 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.

Diagnostic Test:
• Histopathology and Immunohistochemistry
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.

Locations

Country	Name	City	State
India	Dr. Madhumita Premkumar	Sector-12	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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