Prospective Investigation of Cirrhotic Cardiomyopathy in Humans

Prospective Investigation of Cirrhotic Cardiomyopathy in Humans

Cirrhotic Cardiomyopathy (CCM) is a recognized complication of cirrhosis, but understudied despite recent retrospective data suggesting it may be common, affecting one in three patients with decompensated cirrhosis, and associated with significantly increased risk of death and adverse hepatic and cardiac events. Moreover, evidence from preclinical models and children suggest elevated bile acids in the blood may contribute to CCM, but data from adults with cirrhosis are scarce. Therefore, this study will be the first contemporary prospective multicenter investigation of CCM in adults with cirrhosis in the United States. The study will characterize risk factors for CCM, determine its impact on clinical outcomes, and investigate the contribution of circulating bile acids to disease development.

Cirrhotic cardiomyopathy (CCM) is a recognized but understudied and not well understood complication of cirrhosis. CCM is defined as subclinical (i.e., silent) heart dysfunction identified by echocardiography in patients with cirrhosis in the absence of other heart diseases such as significant coronary artery, valvular, or pericardial disease. Initial small studies indicate that CCM is common and it warrants larger prospective study in humans to address unanswered questions highly relevant to clinical care. These include 1) what are the associations between CCM and cirrhosis-related outcomes, adverse cardiac events, and survival 2) what clinical factors increase the risk for CCM, and 3) do bile acids levels, which are produced by the liver, in the blood associate with features of CCM.

Inclusion Criteria:

1. Decompensated cirrhosis, defined as cirrhosis with current or prior occurrence of one or more of the following:

   • portal hypertension-related bleeding,
   • hepatic encephalopathy, and/or
   • clinical ascites.

2. Model for End Stage Liver Disease version 3.0 (MELD 3.0) ≥ 15 or Child Pugh Class B-C

3. Age ≥ 18 years

4. Longitudinal follow up in either at Vanderbilt University Medical Center (VUMC) or University of Texas Southwestern (UTSW) hepatology clinics

5. Willing to adhere to study protocol

6. Able to provide written informed consent

Exclusion Criteria:

1. Current or prior obstructive coronary artery disease, ≥ moderate valvular disease, > mild pericardial effusion, cardiac amyloidosis, congenital heart disease, pacemaker, or implantable cardioverter defibrillator
2. End-stage heart, kidney, or lung disease
3. Pulmonary Arterial Hypertension
4. Acute on Chronic Liver Failure (ACLF) grade 2-3 (i.e., ≥ 2 extrahepatic organ failures)
5. Advanced hepatocellular carcinoma (i.e., Barcelona Clinic Liver Cancer (BCLC) Stage C or D)
6. Ongoing alcohol use, by patient reporting or by phosphatidyl ethanol testing
7. Pregnancy
8. Prior TIPS