Cardiopulmonary Exercise Testing in Cirrhotic Patients: a Pilot Study

Optimizing patient survival and organ utility is a constant struggle for the liver transplant community. Despite rigorous cardiovascular evaluation before liver transplantation cardiovascular events are one of the leading causes of post-transplant morbidity and mortality in both early and late post transplant periods. Poor performance on measures of cardiopulmonary fitness has been associated with worse outcomes in liver transplant candidates. The investigators seek to determine the feasibility of obtaining measures of cardiopulmonary performance in liver transplant candidates from standard cardiopulmonary exercise testing (CPET) and from a modified 3 minute step test and to determine whether the 3 minute step test is suitable for the assessment of cardiopulmonary fitness in a future outcome study.

Subjects: 10 patients ≥40 years of age with cirrhotic end-stage liver disease undergoing liver transplantation evaluation at Mayo Clinic, Rochester, MN. Patients who require multi-organ transplant, or who have non-cirrhotic liver disease (neuroendocrine, amyloidosis, etc.) will be excluded. Each subject will undergo both standard CPET and modified 3 minute step test.

Exercise testing. Subjects will perform both tests during one visit to the cardiopulmonary research lab. A 30-60 minute period between tests will given. 5 patients will perform submaximal stress testing first and 5 will perform the full CPET first.

CPET: Patients will perform a 6 minute cardiopulmonary exercise test using the recumbent stationary bicycle facilitated by the co-investigators at the St Mary's cardiopulmonary exercise laboratory. Standard 12-lead electrocardiograms will be obtained at rest, each minute during exercise, and for at least five minutes during the recovery phase; blood pressure will be measured using a standard cuff sphygmomanometer. Minute ventilation (VE), breathing frequency (fR), tidal volume (VT), oxygen consumption (VO2), CO2 production (VCO2), RER, and end-tidal CO2 (PETCO2) will be obtained breath-by-breath and averaged over a 30-second period at rest and the last 30 seconds of each minute during exercise. In addition, heart rate (HR) and oxygen saturation (SaO2) will be obtained continuously using pulse oximetry. From these data, derived variables such as the VE/VCO2 ratio, oxygen pulse (VO2/HR) and an index of pulmonary capacitance (O2 pulse /\[1/PETCO2\]) are calculated at rest and during exercise. Ventilatory efficiency slopes (VE/VCO2 slope) \[VE liter/min _ m (VCO2, liter/min) _ b\], where m _ VE/VCO2 slope, and oxygen uptake efficiency slopes (OUES) \[VO2, liter/min _ m (log10VE) _ b\], where m _ OUES, are calculated using all exercise data points via least squares linear regression.

Modified 3 minute step test: Each participant will perform a sub-maximal exercise test that consists of 2 minutes of resting baseline, 3 minutes of step exercise, and 1 minute of recovery. Breathing pattern, gas exchange (as described above), and heart rate will be monitored using a simplified gas analysis system (SHAPE Medical Systems, Inc, St. Paul, MN). Submaximal testing will be defined by respiratory exchange ratio (RER), and perceived exertion (RPE). An exercise RER of 0.9 and RPE of 12 to 13 on the Borg scale (range, 6 to 20) is considered to be a sub-maximal level. At the end of the first \& second minute of step exercise, RER and RPE will be recorded and the step rate adjusted (a patient with a low RER (\< 0.8) and RPE (\< 8) would increase the step rate for the second minute, whereas a patient with a higher RER (\> 0.85) and RPE (\> 11) would maintain the same step rate). On completion of the 3-minute step exercise, recovery data will be collected for 1 minute.

Eligibility Criteria:
Inclusion Criteria:

* listed for liver transplantation with end stage liver disease

Exclusion Criteria:

* patients listed for liver transplant without end stage liver disease