Prospective Investigation of Cirrhotic Cardiomyopathy in Humans (PITCH)

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, we are conducting the first contemporary prospective multi-center investigation of CCM in adults in the USA to define CCM risk factors and impact on outcomes while deepening understanding of the role of bile acids in development of this disease.

Study Overview

• Status: Recruiting
• Conditions: Cirrhotic Cardiomyopathy

Detailed Description

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 bi le acids levels, which are produced by the liver, in the blood associate with features of CCM. In this study, we conduct the first US based prospective investigation of CCM in humans with decompensated cirrhosis.

• Study Type: Observational
• Enrollment (Estimated): 440

Contacts and Locations

• Study Contact: Name: Manhal Izzy, MD; Phone Number: 615-875-6540; Email: manhal.izzy@vumc.org
• Study Contact Backup: Name: Deepak Gupta, MD; Email: d.gupta@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Manhal Izzy, MD
      • Contact: Manhal Izzy; Phone Number: MD; Email: manhal.izzy@vumc.org
      • Sub-Investigator: Deepak Gupta, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Lisa VanWagner,, MD; Phone Number: 214-648-3111; Email: Lisa.Vanwagner@UTSouthwestern.edu
      • Sub-Investigator: Lisa Vanwagner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Study population will be identified through clinic referrals and inpatient evaluations.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Cirrhotic cardiomyopathy; Subjects should have decompensated cirrhosis, defined as cirrhosis with current or prior occurrence of one or more of the following: • portal hypertension-related bleeding (a type of bleeding from the gut in patients with cirrhosis),• hepatic encephalopathy (i.e., alteration in mental status due to cirrhosis), and/or • clinical ascites (i.e., fluid build up in the abdomen). The cohort will then be analyzed based on the presence of cirrhotic cardiomyopathy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cirrhosis-related outcomes	Clinical ascites, hepatic encephalopathy, portal hypertension related bleeding, hepatorenal syndrome, portopulmonary hypertension, hepatopulmonary syndrome	1 or more years of follow up (up to 4 years)
Adverse Cardiac Outcomes	Myocardial infarction, Unstable angina, Stable angina, Coronary revascularization, Heart failure, Arrhythmia	1 or more years of follow up (up to 4 years)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Manhal Izzy, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• 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.
• Kajal K, Premkumar M, Izzy M, Kulkarni AV, Duseja AK, Divyaveer S, Loganathan S, Sihag B, Gupta A, Bahl A, Rathi S, Taneja S, De A, Verma N, Sharma N, Kaur H, Zohmangaihi D, Kumar V, Bhujade H, Chaluvashetty SB, Kalra N. Cirrhotic cardiomyopathy influences clinical outcomes and enhances performance of conventional risk prediction models in acute-on-chronic liver failure with severe sepsis. Aliment Pharmacol Ther. 2023 Nov;58(9):903-919. doi: 10.1111/apt.17695. Epub 2023 Sep 9.
• Myers S, Gupta DK, Izzy M. The clinical relevance of the new criteria for cirrhotic cardiomyopathy and future directions. Liver Transpl. 2025 Apr 1;31(4):521-530. doi: 10.1097/LVT.0000000000000458. Epub 2024 Aug 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Cirrhosis; Cirrhotic cardiomyopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fibrosis
• Other Study ID Numbers: 250891; R01HL181174 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No