Clinical trial NCT06095466: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cirrhotic Cardiomyopathy
Cirrhosis, Liver
Cardiac Disease
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2023-10-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Determine the prevalence of cirrhotic cardiomyopathy in critically ill patients with cirrhosis
timeFrame: At Enrollment
Secondary outcomes:
measure: Determine severity of cardiac dysfunction in critically ill patients with cirrhosis
timeFrame: At Enrollment
measure: Determine the POCUS determinants of cardiac dysfunction in critically ill patients with cirrhosis
timeFrame: At Enrollment
measure: Determine the cardiac histology changes in critically ill patients with cirrhosis
timeFrame: At the time of demise
Other outcomes:
Locations:
city: Sector-12
country: India
facility: Dr. Madhumita Premkumar
state: Chandigarh
Study officials:
References:
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.
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.
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.
citation: 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.
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.