Usefulness of Cardiopulmonary Exercise Testing for Cardiovascular Risk Estimation and Frailty Assessment in Liver Transplant Candidates

Patients undergoing liver transplantation (LT) have a high risk for cardiovascular disease (CVD). Frailty is a frequent condition among LT candidates. Together, CVD and frailty are major causes of morbidity and mortality before and after LT. Conventional methods to diagnose and predict CVD in LT candidates lack sensitivity and clinically relevant application. However, cardiopulmonary exercise testing (CPET) can directly estimate coronary artery disease, cirrhotic cardiomyopathy, and indirectly assess frailty. Such versatility of CPET has caused it to become the standard of care in many LT centers outside of the United States.

In preliminary work (funded internally by the Pittsburgh Liver Research Center) that will be used to fund a more definitive study (RO1), the investigators plan to investigate CVD and frailty in LT candidates, both from existing standard of care (SOC) methods and CPET. The investigators expect results to improve the current capacity to assess and prognosticate CVD and frailty in LT, ultimately changing practice.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases+Liver Transplantation
• Intervention / Treatment: Device: Cardiopulmonary exercise testing

Detailed Description

Patients undergoing liver transplantation (LT) have a high risk for cardiovascular disease (CVD). Frailty is a frequent condition among LT candidates. Together, CVD and frailty are major causes of morbidity and mortality before and after LT. Conventional methods to diagnose and predict CVD in LT candidates lack sensitivity and clinically relevant application. However, cardiopulmonary exercise testing (CPET) can directly estimate coronary artery disease, cirrhotic cardiomyopathy, and indirectly assess frailty. Such versatility of CPET has caused it to become the standard of care in many LT centers outside of the United States. In preliminary work that will be used to fund a more definitive study (RO1), the investigators plan to investigate CVD and frailty in LT candidates, both from existing standard of care (SOC) methods and CPET. The investigators expect results to improve the assessment of CVD and frailty in LT, ultimately changing practice. The investigators' proposal will pursue the following Specific Aims (SA):

Aim 1: Prospectively determine agreement between cardiopulmonary exercise testing and cardiac stress testing, for the identification of subclinical coronary artery disease in liver transplant candidates.

Aim 2: Prospectively determine agreement between cardiopulmonary exercise testing and dobutamine stress echocardiogram (DSE) or impedance cardiography, for the identification of cirrhotic cardiomyopathy in liver transplant candidates.

Aim 3: Prospectively determine agreement between peak oxygen consumption from cardiopulmonary exercise testing and the liver frailty index or the six-minute walk test, for the identification of frailty in liver transplant candidates.

• Study Type: Observational
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients waitlisted for a liver transplant or undergoing liver transplant evaluation

Description

Inclusion Criteria:

• Wait listed patients with cirrhosis or those undergoing LT evaluation

Exclusion Criteria:

• Subjects younger than 45 or older than 75 years
• Subjects with platelets <30,000
• Subjects with international normalized range (INR) >3
• Subjects with glomerular filtration rate (GFR) <30
• Subjects with left main artery stenosis
• Subjects with moderate/severe stenotic valvular disease
• Subjects with atrial fibrillation and other arrythmias
• Subjects with resting ventricular ejection fraction <50%
• Subjects with portopulmonary hypertension
• Subjects with severe chronic obstructive pulmonary disease (COPD)
• Subjects with an exercise contraindication

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

CPET; Patients with cirrhosis who have been wait listed for liver transplant or are undergoing liver transplant evaluation and will undergo cardiopulmonary exercise testing (CPET).

Device: Cardiopulmonary exercise testing; Subjects will perform cardiopulmonary exercise testing which consists of biking on a cycle ergometer (recumbant stationary bicycle) while breathing through a mouthpiece or mask to measure the oxygen and carbon dioxide in the subject's breath. We will also do impedance cardiography, an FDA-approved test to check how the heart functions during exercise. For this test we will attach 6 electrodes (total) to the chest and back (similar to an EKG), so that we can measure the quantity of blood coming out of the heart on every heartbeat. Each evaluation will also include cardiac testing looking for coronary artery disease (CAD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiopulmonary exercise testing and cardiac stress testing	Agreement between cardiopulmonary exercise testing and cardiac stress testing, for the identification of subclinical coronary artery disease in liver transplant candidates.	12 months
Cardiopulmonary exercise testing and dobutamine stress echocardiogram	Agreement between cardiopulmonary exercise testing and dobutamine stress echocardiogram (DSE) or impedance cardiography, for the identification of cirrhotic cardiomyopathy in liver transplant candidates.	12 months
Peak oxygen consumption from cardiopulmonary exercise testing	Agreement between peak oxygen consumption from cardiopulmonary exercise testing and the liver frailty index or the six-minute walk test, for the identification of frailty in liver transplant candidates.	12 months

Collaborators and Investigators

• Sponsor: Andres Duarte-Rojo
• Investigators: Principal Investigator: Andres Duarte-Rojo, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: 6-minute walk test, cirrhosis, frailty, major adverse cardiac event
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Frailty
• Other Study ID Numbers: STUDY19100373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigators will construct a REDCap database to collect deidentified research data, as per IRB-approved clinical research form, for a combined analysis of all recruiting centers

Drug and device information, study documents

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