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

Study Overview
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Brief Summary
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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 current capacity to assess and prognosticate CVD and frailty in LT, ultimately changing practice.

Detailed Description
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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 (SOC), 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 (SOC), 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 (SOC), for the identification of frailty in liver transplant candidates.

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

Conditions
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Cardiovascular Diseases+Liver Transplantation

Intervention / Treatment
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* Device: Cardiopulmonary exercise testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Wait listed patients with cirrhosis or those undergoing LT evaluation Exclusion Criteria: Subjects younger than 50 or older than 70 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPET<br>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<br>* 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.<br>|

What is the study measuring?
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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 (SOC), 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 (SOC) to identify 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 to identify frailty in liver transplant candidates | 12 months |