- Email: [email protected]
Enhanced External Counterpulsation
Journal of the American College of Cardiology © 2006 by the American College of Cardiology Foundation Published by Elsevier Inc.
EDITORIAL COMMENT
Enhanced External Counterpulsation Why the Benefit?* Michael F. O’Rourke, MD, DSC, Junichiro Hashimoto, MD Darlinghurst, Australia Forty years ago, after introduction of the intra-aortic balloon (1), counterpulsation was trialed as a method for support of acute heart failure caused by left ventricular (LV) ischemia (2). The first clinical results were published in 1968 (3). The technique applied classic pathophysiologic principles for reducing myocardial oxygen demand (reduction of LV systolic pressure) and increasing capacity for LV coronary flow (increasing aortic pressure throughout diastole) (4,5). This technique, initially applied in cardiogenic shock complicating acute myocardial infarction, is now widely used in cardiac intensive care for stabilizing patients after cardiac surgery and myocardial infarction and in patients with acute heart failure under consideration of transplantation or use of another mechanical device. See page 1208 External counterpulsation was first reported from Tufts New England Medical Center in Boston in 1974 (6). Introduction was partly based on views that altered pulsatile pressure and flow in the coronary vessels could have favorable persisting effects on collateral vessels. External counterpulsation lost favor with success of the intra-aortic balloon method, which was more precise, provided better support, and was better tolerated for circulatory support over days or weeks in critically ill patients. The Tufts view on potential persisting benefit reemerged and led to trials of enhanced external counterpulsation (EECP) in the 1990s, and the MUST-EECP (Multicenter Study on Enhanced External Counterpulsation) in 1999 (7). On the basis of this randomized “placebo-controlled” (gentle pressure) trial, EECP was accepted by the Centers for Medicare and Medicaid Services (CMS) for reimbursement in treatment of patients with refractory Canadian Cardiovascular Society class III to IV angina that in the opinion of a cardiologist or cardiac surgeon was disabling and due to high-risk or inoperable coronary disease. Since the MUST-EECP trial, further studies (but no randomized trials) have been conducted, typically with 35 *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From the St. Vincent’s Clinic/University of New South Wales, Darlinghurst, Australia. Dr. O’Rourke is a founding director of AtCor Medical, Sydney, Australia.
Vol. 48, No. 6, 2006 ISSN 0735-1097/06/$32.00 doi:10.1016/j.jacc.2006.06.036
1-h sessions of counterpulsations over a 7- to 8-week period. Summary details are given in the recently posted CMS report (8). Most have shown benefit in management of angina, but the CMS has declined to extend reimbursement for wider use. In response to initial enquiry (8), CMS received just 79 comments from the public in favor of this, despite urging of manufacturers. Support appears “underwhelming” and is virtually nonexistent outside the U.S. Yet EECP still has support from prominent institutions in the U.S., and there is objective evidence of long-term benefit, though still not in any trial with an appropriately randomized control group. Some of this evidence is given in the paper by Nichols et al. (9) in this issue of the Journal. Nichols et al. (9) reported on a series of 20 patients with refractory but stable angina who completed the usual 35 1-h periods of EECP over a 7- to 8-week period at the University of Florida-Gainesville. The authors sought evidence of change in the peripheral circulation that may explain benefit, on the basis of decrease in LV systolic load and of myocardial blood requirements (4,5). This was found as decrease in large artery stiffness (apparent in delay of wave reflection), decrease in peripheral wave reflection (decrease in aortic augmentation index), and decrease in LV tensiontime index (4) and “wasted energy.” Nichols et al. (9) attributed the benefits to improved endothelial function in peripheral arteries and likened the effects to aerobic exercise training, which also has been shown to reduce wave reflection and thereby reduce central augmentation and aortic and LV systolic pressure (10,11). Nichols et al. (9) used the SphygmoCor system (Atcor Medical Pty Ltd., Sydney, Australia) to assess EECP, as they and others have for exercise (10 –12). All but 1 of their patients improved with EECP, at least to the end of the study period. Others have described benefits lasting for over 1 year from a single course of treatment (8). Benefits of exercise wear off within 1 month (12). Benefits of EECP on endothelial function have been attributed to increased flow shear in large arteries in the legs and into the trunk as a consequence of rhythmic compression to the legs (9). This is the same mechanism as proposed for aerobic exercise (10 –12). Can EECP then be viewed as a form of passive exercise? The answer seems to be yes! The same mechanism as proposed by Nichols et al. (9) (improved endothelial function) has also been proposed by Dockery et al. (13), but those U.K. workers considered that the principal site was in the coronary arteries with resultant improvement in coronary collateral flow. This is the old Tufts hypothesis and is not incompatible with the Nichols et al. (9) findings, because improved endothelial function was attributed to change in pulsatile flow and pressure generated in the legs but passing into the coronary circulation. Dockery et al. did measure carotid augmentation as an index of wave reflection but could find no evidence of reduced wave reflection. Nichols et al. (9) provided a reasonable response to this anomaly. Applanation tonome-
1216
O’Rourke and Hashimoto Editorial Comment
try is notoriously difficult in the carotid arteries (14), and a very experienced group could not demonstrate any benefit of carotid over brachial cuff pressure in predicting outcome of women in the Australian National Blood Pressure 2 trial (15). This is not the experience of others (16). The practical place of EECP in cardiology remains unclear. The CMS review of 2005 (8) could not identify sufficient benefit to extend indications for use but did identify other factors which may be operative, including patients’ greater opportunity to receive, over an extended period, advice on rehabilitation, assistance with exercise programs, and more intensive drug therapy and counseling. Public comments to the CMS enquiry (8) included the same points. The particular value of the Nichols et al. (9) study is that it exposed a mechanism for reducing anginal episodes that might be achieved with less costly and more convenient measures than EECP, including graded exercise, more careful supervision, and better use of medical therapy, including nitrates in patch or oral form. The methods used by Nichols et al. (9) are simple, validated, and reproducible (16). Explanations are logical and cover most of the published observations, as well as anecdotal information provided to the CMS (8). The Tufts group probably was correct in perceiving a long-standing as well as an acute beneficial effect from mechanical modification of the arterial pulse waveform. Reprint requests and correspondence: Dr. Michael F. O’Rourke, Suite 810, St. Vincent’s Clinic, 438 Victoria Street, Darlinghurst, NSW 2010, Australia. E-mail: [email protected].
REFERENCES 1. Moulopoulos SD, Topaz S, Kolff WJ. Diastolic balloon pumping (with carbon dioxide) in the aorta. A mechanical assistance to the failing circulation. Am Heart J 1962;63:669 –75.
JACC Vol. 48, No. 6, 2006 September 19, 2006:1215–6 2. Brown BG, Goldfarb D, Topaz S, Gott V. Diastolic augmentation by intra aortic balloon. Circulatory hemodynamics and treatment of severe acute left ventricular failure in dogs. J Thorac Cardiovasc Surg 1967;53:789 – 804. 3. Kantrowitz A, Tjonneland S, Krakauer J, et al. Clinical experience with cardiac assistance by means of intra-aortic phase-shift balloon pumping. ASAIO J 1968;14:344 – 8. 4. Sarnoff SJ, Braunwald E, Welch GH, et al. Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J Physiol 1958;192:148 –56. 5. Berne RM. Regulation of coronary blood flow. Physiol Rev 1964;44: 1–29. 6. Soroff HS, Cloutier CT, Birtwell WC, Begley LA, Messer JV. External counterpulsation. Management of cardiogenic shock after myocardial infarction. JAMA 1974;229:1441–50. 7. Arora RR, Chou TM, Jain D, et al. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol 1999;33:1833– 40. 8. Centers for Medicare and Medicaid Services. Available at: http:// www.cms.hhs.gov/mcd/viewtrackingsheet.asp?id⫽162. Accessed May 1, 2006. 9. Nichols WW, Estrada JC, Braith RW, Owens K, Conti CR. Enhanced external counterpulsation treatment improves arterial wall properties and wave reflection characteristics in patients with refractory angina. J Am Coll Cardiol 2006;48;1208 –14. 10. Edwards DG, Schofield RS, Magyari PM, Nichols WW, Braith RW. Effect of exercise training on central aortic pressure wave reflection in coronary artery disease. Am J Hypertens 2004;17:540 –3. 11. Edwards DG, Lang JT. Augmentation index and systolic load are lower in competitive endurance athletes. Am J Hypertens 2005;18: 679 – 83. 12. Mustata S, Chan C, Lai V, Miller JA. Impact of an exercise program on arterial stiffness and insulin resistance in hemodialysis patients. J Am Soc Nephrol 2004;15:2713– 8. 13. Dockery F, Rajkumar C, Bulpitt CJ, Hall RJ, Bagger JP. Enhanced external counterpulsation does not alter arterial stiffness in patients with angina. Clin Cardiol 2004;27:689 –92. 14. Adji A, Hirata K, O’Rourke MF. Clinical use of indices determined noninvasively from the radial and carotid pressure waveforms. Blood Press Monitor 2006;11:215–21. 15. Dart AM, Gatzka CD, Kingwell BA, et al. Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives. Hypertension 2006;47:785–90. 16. Nichols WW, O’Rourke MF. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 5th edition. London: Hodder Arnold, 2005.
EDITORIAL COMMENT
Enhanced External Counterpulsation Why the Benefit?* Michael F. O’Rourke, MD, DSC, Junichiro Hashimoto, MD Darlinghurst, Australia Forty years ago, after introduction of the intra-aortic balloon (1), counterpulsation was trialed as a method for support of acute heart failure caused by left ventricular (LV) ischemia (2). The first clinical results were published in 1968 (3). The technique applied classic pathophysiologic principles for reducing myocardial oxygen demand (reduction of LV systolic pressure) and increasing capacity for LV coronary flow (increasing aortic pressure throughout diastole) (4,5). This technique, initially applied in cardiogenic shock complicating acute myocardial infarction, is now widely used in cardiac intensive care for stabilizing patients after cardiac surgery and myocardial infarction and in patients with acute heart failure under consideration of transplantation or use of another mechanical device. See page 1208 External counterpulsation was first reported from Tufts New England Medical Center in Boston in 1974 (6). Introduction was partly based on views that altered pulsatile pressure and flow in the coronary vessels could have favorable persisting effects on collateral vessels. External counterpulsation lost favor with success of the intra-aortic balloon method, which was more precise, provided better support, and was better tolerated for circulatory support over days or weeks in critically ill patients. The Tufts view on potential persisting benefit reemerged and led to trials of enhanced external counterpulsation (EECP) in the 1990s, and the MUST-EECP (Multicenter Study on Enhanced External Counterpulsation) in 1999 (7). On the basis of this randomized “placebo-controlled” (gentle pressure) trial, EECP was accepted by the Centers for Medicare and Medicaid Services (CMS) for reimbursement in treatment of patients with refractory Canadian Cardiovascular Society class III to IV angina that in the opinion of a cardiologist or cardiac surgeon was disabling and due to high-risk or inoperable coronary disease. Since the MUST-EECP trial, further studies (but no randomized trials) have been conducted, typically with 35 *Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From the St. Vincent’s Clinic/University of New South Wales, Darlinghurst, Australia. Dr. O’Rourke is a founding director of AtCor Medical, Sydney, Australia.
Vol. 48, No. 6, 2006 ISSN 0735-1097/06/$32.00 doi:10.1016/j.jacc.2006.06.036
1-h sessions of counterpulsations over a 7- to 8-week period. Summary details are given in the recently posted CMS report (8). Most have shown benefit in management of angina, but the CMS has declined to extend reimbursement for wider use. In response to initial enquiry (8), CMS received just 79 comments from the public in favor of this, despite urging of manufacturers. Support appears “underwhelming” and is virtually nonexistent outside the U.S. Yet EECP still has support from prominent institutions in the U.S., and there is objective evidence of long-term benefit, though still not in any trial with an appropriately randomized control group. Some of this evidence is given in the paper by Nichols et al. (9) in this issue of the Journal. Nichols et al. (9) reported on a series of 20 patients with refractory but stable angina who completed the usual 35 1-h periods of EECP over a 7- to 8-week period at the University of Florida-Gainesville. The authors sought evidence of change in the peripheral circulation that may explain benefit, on the basis of decrease in LV systolic load and of myocardial blood requirements (4,5). This was found as decrease in large artery stiffness (apparent in delay of wave reflection), decrease in peripheral wave reflection (decrease in aortic augmentation index), and decrease in LV tensiontime index (4) and “wasted energy.” Nichols et al. (9) attributed the benefits to improved endothelial function in peripheral arteries and likened the effects to aerobic exercise training, which also has been shown to reduce wave reflection and thereby reduce central augmentation and aortic and LV systolic pressure (10,11). Nichols et al. (9) used the SphygmoCor system (Atcor Medical Pty Ltd., Sydney, Australia) to assess EECP, as they and others have for exercise (10 –12). All but 1 of their patients improved with EECP, at least to the end of the study period. Others have described benefits lasting for over 1 year from a single course of treatment (8). Benefits of exercise wear off within 1 month (12). Benefits of EECP on endothelial function have been attributed to increased flow shear in large arteries in the legs and into the trunk as a consequence of rhythmic compression to the legs (9). This is the same mechanism as proposed for aerobic exercise (10 –12). Can EECP then be viewed as a form of passive exercise? The answer seems to be yes! The same mechanism as proposed by Nichols et al. (9) (improved endothelial function) has also been proposed by Dockery et al. (13), but those U.K. workers considered that the principal site was in the coronary arteries with resultant improvement in coronary collateral flow. This is the old Tufts hypothesis and is not incompatible with the Nichols et al. (9) findings, because improved endothelial function was attributed to change in pulsatile flow and pressure generated in the legs but passing into the coronary circulation. Dockery et al. did measure carotid augmentation as an index of wave reflection but could find no evidence of reduced wave reflection. Nichols et al. (9) provided a reasonable response to this anomaly. Applanation tonome-
1216
O’Rourke and Hashimoto Editorial Comment
try is notoriously difficult in the carotid arteries (14), and a very experienced group could not demonstrate any benefit of carotid over brachial cuff pressure in predicting outcome of women in the Australian National Blood Pressure 2 trial (15). This is not the experience of others (16). The practical place of EECP in cardiology remains unclear. The CMS review of 2005 (8) could not identify sufficient benefit to extend indications for use but did identify other factors which may be operative, including patients’ greater opportunity to receive, over an extended period, advice on rehabilitation, assistance with exercise programs, and more intensive drug therapy and counseling. Public comments to the CMS enquiry (8) included the same points. The particular value of the Nichols et al. (9) study is that it exposed a mechanism for reducing anginal episodes that might be achieved with less costly and more convenient measures than EECP, including graded exercise, more careful supervision, and better use of medical therapy, including nitrates in patch or oral form. The methods used by Nichols et al. (9) are simple, validated, and reproducible (16). Explanations are logical and cover most of the published observations, as well as anecdotal information provided to the CMS (8). The Tufts group probably was correct in perceiving a long-standing as well as an acute beneficial effect from mechanical modification of the arterial pulse waveform. Reprint requests and correspondence: Dr. Michael F. O’Rourke, Suite 810, St. Vincent’s Clinic, 438 Victoria Street, Darlinghurst, NSW 2010, Australia. E-mail: [email protected].
REFERENCES 1. Moulopoulos SD, Topaz S, Kolff WJ. Diastolic balloon pumping (with carbon dioxide) in the aorta. A mechanical assistance to the failing circulation. Am Heart J 1962;63:669 –75.
JACC Vol. 48, No. 6, 2006 September 19, 2006:1215–6 2. Brown BG, Goldfarb D, Topaz S, Gott V. Diastolic augmentation by intra aortic balloon. Circulatory hemodynamics and treatment of severe acute left ventricular failure in dogs. J Thorac Cardiovasc Surg 1967;53:789 – 804. 3. Kantrowitz A, Tjonneland S, Krakauer J, et al. Clinical experience with cardiac assistance by means of intra-aortic phase-shift balloon pumping. ASAIO J 1968;14:344 – 8. 4. Sarnoff SJ, Braunwald E, Welch GH, et al. Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J Physiol 1958;192:148 –56. 5. Berne RM. Regulation of coronary blood flow. Physiol Rev 1964;44: 1–29. 6. Soroff HS, Cloutier CT, Birtwell WC, Begley LA, Messer JV. External counterpulsation. Management of cardiogenic shock after myocardial infarction. JAMA 1974;229:1441–50. 7. Arora RR, Chou TM, Jain D, et al. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol 1999;33:1833– 40. 8. Centers for Medicare and Medicaid Services. Available at: http:// www.cms.hhs.gov/mcd/viewtrackingsheet.asp?id⫽162. Accessed May 1, 2006. 9. Nichols WW, Estrada JC, Braith RW, Owens K, Conti CR. Enhanced external counterpulsation treatment improves arterial wall properties and wave reflection characteristics in patients with refractory angina. J Am Coll Cardiol 2006;48;1208 –14. 10. Edwards DG, Schofield RS, Magyari PM, Nichols WW, Braith RW. Effect of exercise training on central aortic pressure wave reflection in coronary artery disease. Am J Hypertens 2004;17:540 –3. 11. Edwards DG, Lang JT. Augmentation index and systolic load are lower in competitive endurance athletes. Am J Hypertens 2005;18: 679 – 83. 12. Mustata S, Chan C, Lai V, Miller JA. Impact of an exercise program on arterial stiffness and insulin resistance in hemodialysis patients. J Am Soc Nephrol 2004;15:2713– 8. 13. Dockery F, Rajkumar C, Bulpitt CJ, Hall RJ, Bagger JP. Enhanced external counterpulsation does not alter arterial stiffness in patients with angina. Clin Cardiol 2004;27:689 –92. 14. Adji A, Hirata K, O’Rourke MF. Clinical use of indices determined noninvasively from the radial and carotid pressure waveforms. Blood Press Monitor 2006;11:215–21. 15. Dart AM, Gatzka CD, Kingwell BA, et al. Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives. Hypertension 2006;47:785–90. 16. Nichols WW, O’Rourke MF. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 5th edition. London: Hodder Arnold, 2005.