- Email: [email protected]
Comparing Cardiopulmonary Exercise Testing in End-Stage Liver Disease Patients
Comparing Cardiopulmonary Exercise Testing in End-Stage Liver Disease Patients T. Gunnesona, B. Johnsonb, J. Findlayc, M. Joynerb,c, and K.D. Watta,d,* a c
William J. von Liebig Center for Transplantation and Clinical Regeneration; bDepartment of Physiology and Biomedical Engineering; Department of Anesthesia; and dDivision of Gastroenterology/Hepatology; Mayo Clinic, Rochester, Minnesota, USA
ABSTRACT Poor cardiopulmonary fitness has been associated with worse outcomes in liver transplant candidates. Purpose. To determine if a modified 3-minute step test (potentially office based) is feasible and equivalent to standard cardiopulmonary exercise testing (CPET) in liver transplant candidates with severe decompensation. Methods. Five patients with Childs-Pugh C end-stage liver disease and severe debility awaiting liver transplantation performed both standard CPET and the modified 3-minute step test (Shape medical systems). Results. All 5 patients were able to complete both tests. Mean age was 59.8 9 years, mean MELD score was 20 (range 13e26), and mean BMI was 27.6 kg/m2 (range 16.4e37.2). Peak VO2 was similar with a mean of 901 mL/min (step test) compared to 856 mL/min (cycle test), P ¼ .64. VO2 at a respiratory exchange ratio (RER) of 1.0 was similar with both tests (681 mL/min (step) vs 646 mL/min (cycle), P ¼ .69. VE/VCO2 slope (ventilatory efficiency) was similar (40 vs 39, P ¼ .94). The ventilatory compensation point (i.e. anaerobic threshold) was also similar (w80% of peak VO2) for both studies. Conclusion. The modified 3-minute step test provides a simplified, potentially office-based assessment of cardiopulmonary exercise capacity and gas exchange measures as standard testing in patients with decompensated end-stage liver disease, with similar tolerability.
C
ARDIOPULMONARY EXERCISE TESTING (CPET) is a safe, noninvasive means of investigation and characterization of a patient’s functional capacity and reserve [1]. For perioperative risk stratification, CPET outperformed other methods for identifying high-risk surgical patients [2]. CPET testing has been useful for preoperative risk assessment in hepatic resection [3] and in liver transplant candidates [4,5]. Additionally, CPET can be predictive of posttransplant mortality [6]. Drawbacks to CPET testing are time, cost, and the ability of severely decompensated patients to complete the testing. Our goal was to determine if an officebased modified 3-minute step test is equivalent to standard CPET in severely decompensated liver transplant candidates. METHODS Five patients with Childs-Pugh C liver disease and severe debility awaiting liver transplantation provided written informed consent.
The protocol was approved by the Mayo Clinic Institutional Review Board. Patients performed a standard 6-minute recumbent stationary bicycle CPET. Standard 12-lead electrocardiograms were obtained at rest and throughout the test and recovery phases. Minute ventilation (VE), tidal volume (VT), oxygen consumption (VO2), CO2 production (VCO2), respiratory exchange ratio (RER), and end-tidal CO2 (PETCO2) were obtained breath-by-breath and averaged each minute during exercise. Heart rate (HR) and oxygen saturation (SaO2) was obtained continuously using pulse oximetry. The modified 3-minute step test (submaximal) consists of 2 minutes of resting, 3 minutes of step exercise, and 1-minute recovery. Breathing pattern, gas exchange (as described above), and HR was
*Address correspondence to Kymberly D. Watt, MD, Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation CH-10, 200 First St. S.W., Rochester, MN 55905, USA. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.08.012
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2470
Transplantation Proceedings, 47, 2470e2472 (2015)
CARDIOPULMONARY TESTING IN ESLD PATIENTS
2471
DISCUSSION
Table 1. Demographics Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Liver Disease Age (y) Height (cm) Weight (kg) Body mass index (kg/m2) Systolic BP (mm Hg) Heart rate MELD Ascites grade* Encephalopathy* Sarcopenia* Creatinine (mg/dL) Bilirubin (mg/dL) INR Albumin CTP score
NASH 66 188 133 37.2 111 58 18 3 2 3 2 3 1.2 2.6 11
NASH 60 171 102 34.8 106 74 21 2 1 2 1.4 5.3 1.6 2.9 10
HCV 68 171 77 26.3 126 75 12 3 2 3 1.2 1.4 1.1 2.7 10
ALD 60 159.3 41.6 16.4 93 109 26 3 2 3 6.1 2.3 1.3 3.4 10
ALD 45 170 66 23.4 96 78 23 2 2 3 0.8 9.1 2 3.1 10
Abbreviations: NASH, nonalcoholic steatohepatitis; ALD, alcohol related liver disease; BP, blood pressure; MELD, model for end-stage liver disease; INR, international normalized ratio; CPT score, Child-Turcotte-Pugh score. *Scoring system: mild ¼ 1, moderate ¼ 2, severe ¼ 3.
monitored using a simplified gas analysis system (SHAPE Medical Systems Inc., St. Paul, Minn., United States). Submaximal testing was defined by an exercise RER of 0.9 and perceived exertion (RPE) of 12 to 13 on the Borg scale (range, 6e20), whereby the step rate was adjusted (a low RER [<0.8] and RPE [<8] would increase the step rate; a higher RER [>0.85] and RPE [>11] maintained the rate). Subjects completed both tests with a 30-minute rest between tests. The order of testing was reversed with each patient recruited. Statistical analysis was completed using SAS version 9.2 software. Continuous variables were summarized with means, ranges, and standard deviations (SD).
RESULTS
Patient demographics are shown in Table 1. Mean age was 59.8 9 years, and MELD score ranged from 13 to 26. Individual patient exercise data are shown in Table 2. Overall, peak VO2 was similar with a mean of 901 mL/min (step test) compared to 856 mL/min (cycle test), P ¼ .64. VO2 at an RER of 1.0 was similar with both tests (681 mL/min (step) vs 646 mL/min (cycle) (P ¼ .69). Ventilatory efficiency (VE/ VCO2) slope was similar (40 vs 39 units, P ¼ .94). The ventilatory compensation point or anaerobic threshold (AT) was also similar (80% of peak VO2) for both studies.
A simple, cost-effective, and highly predictive test that can identify a high-risk transplant candidate is needed. A 3minute step test may be equally diagnostic, simpler, and more convenient to perform as standard CPET in the endstage liver disease patient. Debilitated patients with ascites and muscle wasting demonstrated tolerability of this testing. In most cases a standard CPET will yield peak data that are higher than those from a 3-minute step test. However, patients with endstage liver disease and fluid overload also develop pulmonary system complications, sarcopenia, and cachexia, which may increase stimulation of muscle afferents, exaggerating the cardiorespiratory responses to exercise. Thus, the 3minute step test can help them achieve near maximum capacity in a shorter time frame. This test could be performed at the patient’s bedside or in an office setting, increasing its ease and portability. CPET testing is an active assessment of an individual’s cardiac and respiratory function. Measures such as anaerobic threshold and peak VO2 demonstrate their overall cardiorespiratory capacity. These measures have been helpful with preoperative risk assessment and have been shown to predict post-transplant mortality [4,6,7]. Similarly, debilitated patients with congestive heart failure and pulmonary hypertension have tolerated this testing with minimal complications or adverse events [8,9]. CONCLUSION
The modified 3-minute step test provides similar assessment of cardiopulmonary exercise capacity and gas exchange measures as standard CPET testing in patients with decompensated end-stage liver disease, with similar tolerability. The 3-minute step test may provide a simplified, potentially office-based, CPET to administer to patients being evaluated for liver transplant candidacy. REFERENCES [1] ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211e77. [2] Hennis PJ, Meale PM, Grocott MP. Cardiopulmonary exercise testing for the evaluation of perioperative risk in noncardiopulmonary surgery. Postgrad Med J 2011;87:550e7. [3] Junejo MA, Mason JM, Sheen AJ, Moore J, Foster P, Atkinson D, et al. Cardiopulmonary exercise testing for preoperative risk assessment before hepatic resection. Br J Surg 2012;99: 1097e104.
Table 2. Exercise Results Patient 1
Peak HR VO2 peak RER at peak VO2 VO2 at RER 1.0 VE/VCO2 slope
Patient 2
Patient 3
Patient 4
Patient 5
Step
Cycle
P value
Step
Cycle
Step
Cycle
Step
Cycle
Step
Cycle
Step
Cycle
101 901 1.09 681 40
102 856 1.19 646 39
.683 .644 .291 .688 .943
120 1317 1.27 1150 38.5
75 1014 1.24 880 36
87 877 0.94 650 47
90 922 1.06 820 49
110 1010 0.94 743 29
125 1183 1.36 846 27
NR 790 1.18 560 36
131 580 1.25 411 34
85 510 1.11 303 47
88 580 1.05 275 51
Abbreviations: HR, heart rate; VE, minute ventilation; VO2, oxygen consumption; VCO2, CO2 production; RER, respiratory exchange ratio; NR, not registered.
2472 [4] Prentis J, Manas D, Trenell M, Hudson M, Jones D, Snowden C. Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation. Liver Transpl 2012;18:152e9. [5] Jones JC, Coombes JS, Macdonald GA. Exercise capacity and muscle strength in patients with cirrhosis. Liver Transpl 2012;18:146e51. [6] Bernal W, Martin-Mateos R, Lipcsey M, Tallis C, Woodsford K, McPhail MJ, et al. Aerobic capacity during cardiopulmonary exercise testing and survival with and without liver transplantation for patients with chronic liver disease. Liver Transpl 2014;20:54e62.
GUNNESON, JOHNSON, FINDLAY ET AL [7] Epstein SK, Freeman RB, Khayat A, Unterborn JN, Pratt DS, Kaplan MM. Aerobic capacity is associated with 100-day outcome after hepatic transplantation. Liver Transpl 2004;10: 418e24. [8] Woods PR, Bailey KR, Wood CM, Johnson BD. Submaximal exercise gas exchange is an important prognostic tool to predict adverse outcomes in heart failure. Eur J Heart Fail 2011;13:303e10. [9] Woods PR, Frantz RP, Taylor BJ, Olson TP, Johnson BD. The usefulness of submaximal exercise gas exchange to define pulmonary arterial hypertension. J Heart Lung Transplant 2011;30: 1133e42.
William J. von Liebig Center for Transplantation and Clinical Regeneration; bDepartment of Physiology and Biomedical Engineering; Department of Anesthesia; and dDivision of Gastroenterology/Hepatology; Mayo Clinic, Rochester, Minnesota, USA
ABSTRACT Poor cardiopulmonary fitness has been associated with worse outcomes in liver transplant candidates. Purpose. To determine if a modified 3-minute step test (potentially office based) is feasible and equivalent to standard cardiopulmonary exercise testing (CPET) in liver transplant candidates with severe decompensation. Methods. Five patients with Childs-Pugh C end-stage liver disease and severe debility awaiting liver transplantation performed both standard CPET and the modified 3-minute step test (Shape medical systems). Results. All 5 patients were able to complete both tests. Mean age was 59.8 9 years, mean MELD score was 20 (range 13e26), and mean BMI was 27.6 kg/m2 (range 16.4e37.2). Peak VO2 was similar with a mean of 901 mL/min (step test) compared to 856 mL/min (cycle test), P ¼ .64. VO2 at a respiratory exchange ratio (RER) of 1.0 was similar with both tests (681 mL/min (step) vs 646 mL/min (cycle), P ¼ .69. VE/VCO2 slope (ventilatory efficiency) was similar (40 vs 39, P ¼ .94). The ventilatory compensation point (i.e. anaerobic threshold) was also similar (w80% of peak VO2) for both studies. Conclusion. The modified 3-minute step test provides a simplified, potentially office-based assessment of cardiopulmonary exercise capacity and gas exchange measures as standard testing in patients with decompensated end-stage liver disease, with similar tolerability.
C
ARDIOPULMONARY EXERCISE TESTING (CPET) is a safe, noninvasive means of investigation and characterization of a patient’s functional capacity and reserve [1]. For perioperative risk stratification, CPET outperformed other methods for identifying high-risk surgical patients [2]. CPET testing has been useful for preoperative risk assessment in hepatic resection [3] and in liver transplant candidates [4,5]. Additionally, CPET can be predictive of posttransplant mortality [6]. Drawbacks to CPET testing are time, cost, and the ability of severely decompensated patients to complete the testing. Our goal was to determine if an officebased modified 3-minute step test is equivalent to standard CPET in severely decompensated liver transplant candidates. METHODS Five patients with Childs-Pugh C liver disease and severe debility awaiting liver transplantation provided written informed consent.
The protocol was approved by the Mayo Clinic Institutional Review Board. Patients performed a standard 6-minute recumbent stationary bicycle CPET. Standard 12-lead electrocardiograms were obtained at rest and throughout the test and recovery phases. Minute ventilation (VE), tidal volume (VT), oxygen consumption (VO2), CO2 production (VCO2), respiratory exchange ratio (RER), and end-tidal CO2 (PETCO2) were obtained breath-by-breath and averaged each minute during exercise. Heart rate (HR) and oxygen saturation (SaO2) was obtained continuously using pulse oximetry. The modified 3-minute step test (submaximal) consists of 2 minutes of resting, 3 minutes of step exercise, and 1-minute recovery. Breathing pattern, gas exchange (as described above), and HR was
*Address correspondence to Kymberly D. Watt, MD, Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation CH-10, 200 First St. S.W., Rochester, MN 55905, USA. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.08.012
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2470
Transplantation Proceedings, 47, 2470e2472 (2015)
CARDIOPULMONARY TESTING IN ESLD PATIENTS
2471
DISCUSSION
Table 1. Demographics Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Liver Disease Age (y) Height (cm) Weight (kg) Body mass index (kg/m2) Systolic BP (mm Hg) Heart rate MELD Ascites grade* Encephalopathy* Sarcopenia* Creatinine (mg/dL) Bilirubin (mg/dL) INR Albumin CTP score
NASH 66 188 133 37.2 111 58 18 3 2 3 2 3 1.2 2.6 11
NASH 60 171 102 34.8 106 74 21 2 1 2 1.4 5.3 1.6 2.9 10
HCV 68 171 77 26.3 126 75 12 3 2 3 1.2 1.4 1.1 2.7 10
ALD 60 159.3 41.6 16.4 93 109 26 3 2 3 6.1 2.3 1.3 3.4 10
ALD 45 170 66 23.4 96 78 23 2 2 3 0.8 9.1 2 3.1 10
Abbreviations: NASH, nonalcoholic steatohepatitis; ALD, alcohol related liver disease; BP, blood pressure; MELD, model for end-stage liver disease; INR, international normalized ratio; CPT score, Child-Turcotte-Pugh score. *Scoring system: mild ¼ 1, moderate ¼ 2, severe ¼ 3.
monitored using a simplified gas analysis system (SHAPE Medical Systems Inc., St. Paul, Minn., United States). Submaximal testing was defined by an exercise RER of 0.9 and perceived exertion (RPE) of 12 to 13 on the Borg scale (range, 6e20), whereby the step rate was adjusted (a low RER [<0.8] and RPE [<8] would increase the step rate; a higher RER [>0.85] and RPE [>11] maintained the rate). Subjects completed both tests with a 30-minute rest between tests. The order of testing was reversed with each patient recruited. Statistical analysis was completed using SAS version 9.2 software. Continuous variables were summarized with means, ranges, and standard deviations (SD).
RESULTS
Patient demographics are shown in Table 1. Mean age was 59.8 9 years, and MELD score ranged from 13 to 26. Individual patient exercise data are shown in Table 2. Overall, peak VO2 was similar with a mean of 901 mL/min (step test) compared to 856 mL/min (cycle test), P ¼ .64. VO2 at an RER of 1.0 was similar with both tests (681 mL/min (step) vs 646 mL/min (cycle) (P ¼ .69). Ventilatory efficiency (VE/ VCO2) slope was similar (40 vs 39 units, P ¼ .94). The ventilatory compensation point or anaerobic threshold (AT) was also similar (80% of peak VO2) for both studies.
A simple, cost-effective, and highly predictive test that can identify a high-risk transplant candidate is needed. A 3minute step test may be equally diagnostic, simpler, and more convenient to perform as standard CPET in the endstage liver disease patient. Debilitated patients with ascites and muscle wasting demonstrated tolerability of this testing. In most cases a standard CPET will yield peak data that are higher than those from a 3-minute step test. However, patients with endstage liver disease and fluid overload also develop pulmonary system complications, sarcopenia, and cachexia, which may increase stimulation of muscle afferents, exaggerating the cardiorespiratory responses to exercise. Thus, the 3minute step test can help them achieve near maximum capacity in a shorter time frame. This test could be performed at the patient’s bedside or in an office setting, increasing its ease and portability. CPET testing is an active assessment of an individual’s cardiac and respiratory function. Measures such as anaerobic threshold and peak VO2 demonstrate their overall cardiorespiratory capacity. These measures have been helpful with preoperative risk assessment and have been shown to predict post-transplant mortality [4,6,7]. Similarly, debilitated patients with congestive heart failure and pulmonary hypertension have tolerated this testing with minimal complications or adverse events [8,9]. CONCLUSION
The modified 3-minute step test provides similar assessment of cardiopulmonary exercise capacity and gas exchange measures as standard CPET testing in patients with decompensated end-stage liver disease, with similar tolerability. The 3-minute step test may provide a simplified, potentially office-based, CPET to administer to patients being evaluated for liver transplant candidacy. REFERENCES [1] ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211e77. [2] Hennis PJ, Meale PM, Grocott MP. Cardiopulmonary exercise testing for the evaluation of perioperative risk in noncardiopulmonary surgery. Postgrad Med J 2011;87:550e7. [3] Junejo MA, Mason JM, Sheen AJ, Moore J, Foster P, Atkinson D, et al. Cardiopulmonary exercise testing for preoperative risk assessment before hepatic resection. Br J Surg 2012;99: 1097e104.
Table 2. Exercise Results Patient 1
Peak HR VO2 peak RER at peak VO2 VO2 at RER 1.0 VE/VCO2 slope
Patient 2
Patient 3
Patient 4
Patient 5
Step
Cycle
P value
Step
Cycle
Step
Cycle
Step
Cycle
Step
Cycle
Step
Cycle
101 901 1.09 681 40
102 856 1.19 646 39
.683 .644 .291 .688 .943
120 1317 1.27 1150 38.5
75 1014 1.24 880 36
87 877 0.94 650 47
90 922 1.06 820 49
110 1010 0.94 743 29
125 1183 1.36 846 27
NR 790 1.18 560 36
131 580 1.25 411 34
85 510 1.11 303 47
88 580 1.05 275 51
Abbreviations: HR, heart rate; VE, minute ventilation; VO2, oxygen consumption; VCO2, CO2 production; RER, respiratory exchange ratio; NR, not registered.
2472 [4] Prentis J, Manas D, Trenell M, Hudson M, Jones D, Snowden C. Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation. Liver Transpl 2012;18:152e9. [5] Jones JC, Coombes JS, Macdonald GA. Exercise capacity and muscle strength in patients with cirrhosis. Liver Transpl 2012;18:146e51. [6] Bernal W, Martin-Mateos R, Lipcsey M, Tallis C, Woodsford K, McPhail MJ, et al. Aerobic capacity during cardiopulmonary exercise testing and survival with and without liver transplantation for patients with chronic liver disease. Liver Transpl 2014;20:54e62.
GUNNESON, JOHNSON, FINDLAY ET AL [7] Epstein SK, Freeman RB, Khayat A, Unterborn JN, Pratt DS, Kaplan MM. Aerobic capacity is associated with 100-day outcome after hepatic transplantation. Liver Transpl 2004;10: 418e24. [8] Woods PR, Bailey KR, Wood CM, Johnson BD. Submaximal exercise gas exchange is an important prognostic tool to predict adverse outcomes in heart failure. Eur J Heart Fail 2011;13:303e10. [9] Woods PR, Frantz RP, Taylor BJ, Olson TP, Johnson BD. The usefulness of submaximal exercise gas exchange to define pulmonary arterial hypertension. J Heart Lung Transplant 2011;30: 1133e42.