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

Official title

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

Overview

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.

Interventions

• 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
• 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 o

Primary outcome measures

• Determine the prevalence of cirrhotic cardiomyopathy in critically ill patients with cirrhosis [Time frame: At Enrollment]

Secondary outcome measures (3)

• Determine severity of cardiac dysfunction in critically ill patients with cirrhosis [Time frame: At Enrollment]
• Determine the POCUS determinants of cardiac dysfunction in critically ill patients with cirrhosis [Time frame: At Enrollment]
• Determine the cardiac histology changes in critically ill patients with cirrhosis [Time frame: At the time of demise]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

India · 1 center

• Dr. Madhumita Premkumar — Sector-12

Publications

• 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
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT06095466 · INT/IEC/2023/SPL-963

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗