- Email: [email protected]
Remix
Journal of the American College of Cardiology © 2009 by the American College of Cardiology Foundation Published by Elsevier Inc.
EDITORIAL COMMENT
Remix Exercise Training and Cardiac Resynchronization Therapy in Heart Failure*
Vol. 53, No. 25, 2009 ISSN 0735-1097/09/$36.00 doi:10.1016/j.jacc.2009.03.036
recommendation appeared as part of the current ACC/ AHA guidelines for patients with current or prior symptoms of heart failure with reduced systolic function: ExT is a Class I recommendation (Level of Evidence: B) (5). Recently published in the Journal, a meta-analysis that examined the type of exercise found beneficial ventricular remodeling (negative remodeling) and increased ejection fraction in aerobic (endurance) but not in isometric (strength) ExT programs (6).
Stanley A. Rubin, MD Los Angeles, California
“Remix culture” is a term employed by Lawrence Lessig and other copyright activists to describe a society that allows and encourages derivative works. Lessig presents this as a desirable ideal and argues, among other things, that the health, progress, and wealth creation of a culture is fundamentally tied to this participatory remix process (1). The borrowing, adaptation, and extension of ideas are major forces that drive creativity and lead to improvement in health care, including treatment of cardiovascular disease. For example, exercise training (ExT), also known as “rehabilitation,” recently extended from the conventional indication, post-myocardial infarction, to the less-conventional indication, systolic dysfunction heart failure, as summarized by Rubin (2). Enter “remix”: ExT of heart failure patients who receive a cardiac resynchronization therapy (CRT) (biventricular pacing) device. See page 2332
ExT in Heart Failure Promotes Clinical Benefit
Previous reviews and meta-analyses have demonstrated a plethora of beneficial effects of ExT in patients who have systolic dysfunction heart failure. Summarized, for example, in a Cochrane review, ExT resulted in modest increases of peak exercise oxygen uptake (VO2) (peak VO2 range: 10% to 30% increase), duration of exercise, work capacity, and distance on the 6-min walk test. Improvements in peak VO2 were greater in training programs of greater intensity and duration. Furthermore, health-related quality of life improved in patients in trials that measured this outcome in a heart failure questionnaire instrument (3). On the basis of available evidence, first an American College of Cardiology/ American Heart Association (ACC/AHA) guideline statement update recommended ExT in patients with heart failure (4). Subsequently, a formalized recognition of this
*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 Department of Veteran Affairs, Greater Los Angeles, and the Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, California.
“Hard” End Points Might Elude ExT in Heart Failure
However, other major benefits of this training, including improved survival and decreased hospital stay, are less clear. A consortium of European investigators reported improved survival in a collaborative meta-analysis that examined death from all causes in ExT trials of heart failure. In these endurance training trials, exercise significantly reduced both mortality and death plus hospital admission (7). However, a recently concluded, large, multicenter National Institutes of Health-sponsored trial of ExT in heart failure, HFACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), recently reported a failure to achieve the primary end point of improved survival and decreased hospital stay (8). We await publication of substudies and additional outcomes from this comprehensive trial.
ExT Provides Additional Benefit in Patients Receiving CRT
A previously published pilot trial of a small number of patients suggested that functional capacity further improved by addition of ExT to CRT device implant (9). The study by Patwala et al. (10) reported in this issue of the Journal extends that pilot study in 50 randomized patients with measurements not only of functional capacity but also quality of life. After a waiting period of 3 months after device implantation, so as to establish a new baseline to allow effect/benefit of CRT, the methods of the study included patient randomization to conventional therapy or a typical supervised training program during a subsequent 3-month period, while maintaining medical therapy. The authors report that, as previously demonstrated, CRT alone proved beneficial in functional capacity (peak VO2) as well as improved quality of life. Furthermore, adding ExT caused further improvement in both of these measures as well as New York Heart Association functional class when compared with the conventional therapy group. Therefore, the new information provided in this article is that ExT added further benefit to exercise capacity and functional class, and yielded improved scores on a validated heart failure questionnaire.
Rubin Exercise Training and Resynchronization Therapy
JACC Vol. 53, No. 25, 2009 June 23, 2009:2340–2
2341
Questions and Answers About ExT in Heart Failure
Remix Redux
In a previous editorial in the Journal, I provided an outline of heart failure patients who are likely to benefit from ExT (2). Here, I update my thoughts on the issue with the current results in mind.
Future application of ExT in heart failure should explore issues of venue, duration of training, and type/ pathophysiology of heart failure. With respect to venue, most studies employed ExT in a supervised health care environment. Although initial patient screening and instruction should be performed in this environment, it will be important to see whether this can be moved to an unsupervised environment. This is particularly important with respect to the duration of training. Extrapolating from training studies in typical subjects, functional benefit begins to erode when the training stops. Under the rubric of “use it or lose it,” it is likely that ExT needs to be continued indefinitely to afford the patient continued benefit. It is important to determine the feasibility, safety, and ultimately the long-term benefit of such a program. With respect to pathophysiology, the unsolved riddle of the management of heart failure with normal systolic function (so-called “diastolic dysfunction”) continues to defy tractability. Given the broad cardiovascular effects of ExT and the exasperating lack of effective treatments for this group of patients, it is not unreasonable to propose such a trial. But, even if it cannot be ubiquitously applied, ExT continues to demonstrate value as a “remix” in an ever-increasing group of heart failure management strategies.
1. Is the concept of ExT added to CRT device implant now proved? From the standpoint of functional improvement and quality of life, I would say a qualified “yes.” A larger trial will likely reinforce that conclusion and, perhaps, tackle the elusive prize of increased survival and decreased hospital stay. In further studies, optimal medical therapy, including beta- and renin-angiotensin-aldosterone blockers, needs to find its way to a higher percentage of patients than the approximately 60% reported in the current study. 2. Is the “juice” worth the “squeeze?” Probably “yes.” The benefits of ExT largely resolve to a small increase in functional capacity and quality of life, perhaps a 20% increase in functional capacity, or, in a measurement perhaps more easily assimilated by a clinician, approximately 1 metabolic equivalent. That is enough to permit patients to do a bit more in their lives. Although this and other measures of improved “soft” end points are, perhaps, not as meaningful as improved “hard” end points of increased survival and reduced hospital stays, most patients and physicians would welcome the benefit afforded. The risk, at least when performed in a supervised environment as employed in virtually all studies of ExT in heart failure, is minimal. 3. Is every patient eligible for this form of therapy? Eligibility: “yes.” Advisability: “no.” Among the systolic dysfunction heart failure population, patients who have significant aortic stenosis are precluded. Concomitant illness that impairs locomotion and the movement of large muscle groups also prohibits training. Training also involves patient effort and health care resources, both of which depend on the patient and his or her health insurance. The former requires effort and motivation, whereas the latter requires money. In general, in the U.S., health care insurance and Medicare will not pay for this type of rehabilitation. So, the financial burden on the patient who engages in this might be considerable. 4. What are the indications/contraindications/types of exercise programs? In a previous editorial in the Journal, I provided some advice and a summary table to assist the clinician in screening and selecting appropriate patients as well as the type of exercise program employed (2). Screening should demonstrate a heart failure patient who is clinically stable and medically optimized. The type of training should emphasize endurance (also called “aerobic” or “dynamic” exercise) with a modicum of strength (“isometric”) training added to the program.
Acknowledgments
The author appreciates Joshua N. Rubin for introducing him to the concept of “remix culture,” and the writings and lectures of Lawrence Lessig. Reprint requests and correspondence: Dr. Stanley A. Rubin, VA-UCLA Medical Program, VA Medical Center (111E), 11301 Wilshire Boulevard, Los Angeles, California 90073. E-mail: [email protected]. REFERENCES
1. Remix culture. Available at: http://en.wikipedia.org/w/index. php?title⫽Remix_culture&oldid⫽268105090. Accessed February 20, 2009. 2. Rubin SA. Exercise training in heart failure: contradictory or conventional? J Am Coll Cardiol 2007;49:2337– 40. 3. Rees K, Taylor RS, Singh S, Coats AJS, Ebrahim S. Exercise based rehabilitation for heart failure. Cochrane Database Syst Rev 2004;3: CD003331. 4. Pina IL, Apstein CS, Balady GJ, et al., for the American Heart Association Committee on exercise, rehabilitation, and prevention. Exercise and heart failure: a statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation 2003;107:1210 –25. 5. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:e1– 82. 6. Haykowsky MJ, Liang Y, Pechter D, et al. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. J Am Coll Cardiol 2007;49:2329 –36.
2342
Rubin Exercise Training and Resynchronization Therapy
7. Piepoli MF, Davos C, Francis DP, Coats AJ, for the ExTraMATCH Collaborative. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH). BMJ 2004;328:189. 8. O’Connor CM, Whellan DJ, Lee KL, et al., for the HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1439 –50. 9. Conraads VM, Vanderheyden M, Paelinck B, et al. The effect of endurance training on exercise capacity following cardiac resynchroni-
JACC Vol. 53, No. 25, 2009 June 23, 2009:2340–2 zation therapy in chronic heart failure patients: a pilot trial. Eur J Cardiovasc Prev Rehabil 2007;14:99 –106. 10. Patwala AY, Woods PR, Sharp L, Goldspink DF, Tan LB, Wright DJ. Maximizing patient benefit from cardiac resynchronization therapy with the addition of structured exercise training: a randomized controlled study. J Am Coll Cardiol 2009;53:2332–9. Key Words: cardiac resynchronization therapy y exercise testing y exercise training y heart failure y skeletal muscle.
EDITORIAL COMMENT
Remix Exercise Training and Cardiac Resynchronization Therapy in Heart Failure*
Vol. 53, No. 25, 2009 ISSN 0735-1097/09/$36.00 doi:10.1016/j.jacc.2009.03.036
recommendation appeared as part of the current ACC/ AHA guidelines for patients with current or prior symptoms of heart failure with reduced systolic function: ExT is a Class I recommendation (Level of Evidence: B) (5). Recently published in the Journal, a meta-analysis that examined the type of exercise found beneficial ventricular remodeling (negative remodeling) and increased ejection fraction in aerobic (endurance) but not in isometric (strength) ExT programs (6).
Stanley A. Rubin, MD Los Angeles, California
“Remix culture” is a term employed by Lawrence Lessig and other copyright activists to describe a society that allows and encourages derivative works. Lessig presents this as a desirable ideal and argues, among other things, that the health, progress, and wealth creation of a culture is fundamentally tied to this participatory remix process (1). The borrowing, adaptation, and extension of ideas are major forces that drive creativity and lead to improvement in health care, including treatment of cardiovascular disease. For example, exercise training (ExT), also known as “rehabilitation,” recently extended from the conventional indication, post-myocardial infarction, to the less-conventional indication, systolic dysfunction heart failure, as summarized by Rubin (2). Enter “remix”: ExT of heart failure patients who receive a cardiac resynchronization therapy (CRT) (biventricular pacing) device. See page 2332
ExT in Heart Failure Promotes Clinical Benefit
Previous reviews and meta-analyses have demonstrated a plethora of beneficial effects of ExT in patients who have systolic dysfunction heart failure. Summarized, for example, in a Cochrane review, ExT resulted in modest increases of peak exercise oxygen uptake (VO2) (peak VO2 range: 10% to 30% increase), duration of exercise, work capacity, and distance on the 6-min walk test. Improvements in peak VO2 were greater in training programs of greater intensity and duration. Furthermore, health-related quality of life improved in patients in trials that measured this outcome in a heart failure questionnaire instrument (3). On the basis of available evidence, first an American College of Cardiology/ American Heart Association (ACC/AHA) guideline statement update recommended ExT in patients with heart failure (4). Subsequently, a formalized recognition of this
*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 Department of Veteran Affairs, Greater Los Angeles, and the Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, California.
“Hard” End Points Might Elude ExT in Heart Failure
However, other major benefits of this training, including improved survival and decreased hospital stay, are less clear. A consortium of European investigators reported improved survival in a collaborative meta-analysis that examined death from all causes in ExT trials of heart failure. In these endurance training trials, exercise significantly reduced both mortality and death plus hospital admission (7). However, a recently concluded, large, multicenter National Institutes of Health-sponsored trial of ExT in heart failure, HFACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), recently reported a failure to achieve the primary end point of improved survival and decreased hospital stay (8). We await publication of substudies and additional outcomes from this comprehensive trial.
ExT Provides Additional Benefit in Patients Receiving CRT
A previously published pilot trial of a small number of patients suggested that functional capacity further improved by addition of ExT to CRT device implant (9). The study by Patwala et al. (10) reported in this issue of the Journal extends that pilot study in 50 randomized patients with measurements not only of functional capacity but also quality of life. After a waiting period of 3 months after device implantation, so as to establish a new baseline to allow effect/benefit of CRT, the methods of the study included patient randomization to conventional therapy or a typical supervised training program during a subsequent 3-month period, while maintaining medical therapy. The authors report that, as previously demonstrated, CRT alone proved beneficial in functional capacity (peak VO2) as well as improved quality of life. Furthermore, adding ExT caused further improvement in both of these measures as well as New York Heart Association functional class when compared with the conventional therapy group. Therefore, the new information provided in this article is that ExT added further benefit to exercise capacity and functional class, and yielded improved scores on a validated heart failure questionnaire.
Rubin Exercise Training and Resynchronization Therapy
JACC Vol. 53, No. 25, 2009 June 23, 2009:2340–2
2341
Questions and Answers About ExT in Heart Failure
Remix Redux
In a previous editorial in the Journal, I provided an outline of heart failure patients who are likely to benefit from ExT (2). Here, I update my thoughts on the issue with the current results in mind.
Future application of ExT in heart failure should explore issues of venue, duration of training, and type/ pathophysiology of heart failure. With respect to venue, most studies employed ExT in a supervised health care environment. Although initial patient screening and instruction should be performed in this environment, it will be important to see whether this can be moved to an unsupervised environment. This is particularly important with respect to the duration of training. Extrapolating from training studies in typical subjects, functional benefit begins to erode when the training stops. Under the rubric of “use it or lose it,” it is likely that ExT needs to be continued indefinitely to afford the patient continued benefit. It is important to determine the feasibility, safety, and ultimately the long-term benefit of such a program. With respect to pathophysiology, the unsolved riddle of the management of heart failure with normal systolic function (so-called “diastolic dysfunction”) continues to defy tractability. Given the broad cardiovascular effects of ExT and the exasperating lack of effective treatments for this group of patients, it is not unreasonable to propose such a trial. But, even if it cannot be ubiquitously applied, ExT continues to demonstrate value as a “remix” in an ever-increasing group of heart failure management strategies.
1. Is the concept of ExT added to CRT device implant now proved? From the standpoint of functional improvement and quality of life, I would say a qualified “yes.” A larger trial will likely reinforce that conclusion and, perhaps, tackle the elusive prize of increased survival and decreased hospital stay. In further studies, optimal medical therapy, including beta- and renin-angiotensin-aldosterone blockers, needs to find its way to a higher percentage of patients than the approximately 60% reported in the current study. 2. Is the “juice” worth the “squeeze?” Probably “yes.” The benefits of ExT largely resolve to a small increase in functional capacity and quality of life, perhaps a 20% increase in functional capacity, or, in a measurement perhaps more easily assimilated by a clinician, approximately 1 metabolic equivalent. That is enough to permit patients to do a bit more in their lives. Although this and other measures of improved “soft” end points are, perhaps, not as meaningful as improved “hard” end points of increased survival and reduced hospital stays, most patients and physicians would welcome the benefit afforded. The risk, at least when performed in a supervised environment as employed in virtually all studies of ExT in heart failure, is minimal. 3. Is every patient eligible for this form of therapy? Eligibility: “yes.” Advisability: “no.” Among the systolic dysfunction heart failure population, patients who have significant aortic stenosis are precluded. Concomitant illness that impairs locomotion and the movement of large muscle groups also prohibits training. Training also involves patient effort and health care resources, both of which depend on the patient and his or her health insurance. The former requires effort and motivation, whereas the latter requires money. In general, in the U.S., health care insurance and Medicare will not pay for this type of rehabilitation. So, the financial burden on the patient who engages in this might be considerable. 4. What are the indications/contraindications/types of exercise programs? In a previous editorial in the Journal, I provided some advice and a summary table to assist the clinician in screening and selecting appropriate patients as well as the type of exercise program employed (2). Screening should demonstrate a heart failure patient who is clinically stable and medically optimized. The type of training should emphasize endurance (also called “aerobic” or “dynamic” exercise) with a modicum of strength (“isometric”) training added to the program.
Acknowledgments
The author appreciates Joshua N. Rubin for introducing him to the concept of “remix culture,” and the writings and lectures of Lawrence Lessig. Reprint requests and correspondence: Dr. Stanley A. Rubin, VA-UCLA Medical Program, VA Medical Center (111E), 11301 Wilshire Boulevard, Los Angeles, California 90073. E-mail: [email protected]. REFERENCES
1. Remix culture. Available at: http://en.wikipedia.org/w/index. php?title⫽Remix_culture&oldid⫽268105090. Accessed February 20, 2009. 2. Rubin SA. Exercise training in heart failure: contradictory or conventional? J Am Coll Cardiol 2007;49:2337– 40. 3. Rees K, Taylor RS, Singh S, Coats AJS, Ebrahim S. Exercise based rehabilitation for heart failure. Cochrane Database Syst Rev 2004;3: CD003331. 4. Pina IL, Apstein CS, Balady GJ, et al., for the American Heart Association Committee on exercise, rehabilitation, and prevention. Exercise and heart failure: a statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation 2003;107:1210 –25. 5. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:e1– 82. 6. Haykowsky MJ, Liang Y, Pechter D, et al. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. J Am Coll Cardiol 2007;49:2329 –36.
2342
Rubin Exercise Training and Resynchronization Therapy
7. Piepoli MF, Davos C, Francis DP, Coats AJ, for the ExTraMATCH Collaborative. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH). BMJ 2004;328:189. 8. O’Connor CM, Whellan DJ, Lee KL, et al., for the HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1439 –50. 9. Conraads VM, Vanderheyden M, Paelinck B, et al. The effect of endurance training on exercise capacity following cardiac resynchroni-
JACC Vol. 53, No. 25, 2009 June 23, 2009:2340–2 zation therapy in chronic heart failure patients: a pilot trial. Eur J Cardiovasc Prev Rehabil 2007;14:99 –106. 10. Patwala AY, Woods PR, Sharp L, Goldspink DF, Tan LB, Wright DJ. Maximizing patient benefit from cardiac resynchronization therapy with the addition of structured exercise training: a randomized controlled study. J Am Coll Cardiol 2009;53:2332–9. Key Words: cardiac resynchronization therapy y exercise testing y exercise training y heart failure y skeletal muscle.