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.

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.

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

Patients waitlisted for a liver transplant or undergoing liver transplant evaluation

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