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Cardiac Rehabilitation

The Mandate Grows
  • Daniel E. Forman
    Correspondence
    Correspondence: Address to Daniel E. Forman, MD, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, 3471 Fifth Ave, Ste 500, Pittsburgh, PA 15213.
    Affiliations
    Section of Geriatric Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA
    Division of Cardiology, VA Pittsburgh Healthcare System, Pittsburgh, PA
    Professor of Medicine (pending), University of Pittsburgh, Pittsburgh, PA
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      Articles that focus on cardiac rehabilitation (CR) are increasingly being published in Mayo Clinic Proceedings and other prominent journals,
      • Sandesara P.B.
      • Lambert C.T.
      • Gordon N.F.
      • et al.
      Cardiac rehabilitation and risk reduction: time to “rebrand and reinvigorate.”.
      • Franklin B.A.
      • Brinks J.
      Cardiac rehabilitation: underrecognized/underutilized.
      • Leggett L.E.
      • Hauer T.
      • Martin B.J.
      • et al.
      Optimizing value from cardiac rehabilitation: a cost-utility analysis comparing age, sex, and clinical subgroups.
      • Arena R.
      • Guazzi M.
      • Lianov L.
      • et al.
      Healthy lifestyle interventions to combat noncommunicable disease—a novel nonhierarchical connectivity model for key stakeholders: a policy statement from the American Heart Association, European Society of Cardiology, European Association for Cardiovascular Prevention and Rehabilitation, and American College of Preventive Medicine.
      • Aragam K.G.
      • Dai D.
      • Neely M.L.
      • et al.
      Gaps in referral to cardiac rehabilitation of patients undergoing percutaneous coronary intervention in the United States.
      and they are being afforded prominence in these journals that is coequal to other aspects of cardiovascular (CV) therapy. A tacit inference is that overall healthfulness and self-care are interconnected with other CV treatments, eg, drug therapy and electrotherapy. Physical activity, diet, mood, quality sleep, and other components of basic well-being cannot be assumed, and poor self-care undermines even perfectly executed therapeutic interventions. One glance in almost any cardiology waiting room provides ample evidence that sedentariness, obesity, and other health deficiencies are endemic and associated with detrimental effects. Therefore, CR stands out as an important tool in the traditional medical armamentarium to promote healthfulness and enhance therapeutic efficacy.
      • Sandesara P.B.
      • Lambert C.T.
      • Gordon N.F.
      • et al.
      Cardiac rehabilitation and risk reduction: time to “rebrand and reinvigorate.”.
      • Franklin B.A.
      • Brinks J.
      Cardiac rehabilitation: underrecognized/underutilized.
      • Leggett L.E.
      • Hauer T.
      • Martin B.J.
      • et al.
      Optimizing value from cardiac rehabilitation: a cost-utility analysis comparing age, sex, and clinical subgroups.
      The present issue of Mayo Clinic Proceedings features 3 studies pertaining to CR. In this issue, Rosenbaum et al
      • Rosenbaum A.N.
      • Kremers W.K.
      • Schriger J.A.
      • et al.
      Association between early cardiac rehabilitation and long-term survival in cardiac transplant recipients.
      analyze the utility of CR for heart transplant (HTx) patients; Shaya et al
      • Shaya G.E.
      • Al-Mallah M.H.
      • Hung R.K.
      • et al.
      High exercise capacity attenuates the risk of early mortality after a first myocardial infarction: the Henry Ford Exercise Testing (FIT) Project.
      assess baseline exercise capacity in patients without previous myocardial infarction (MI) and its bearing on outcomes after a subsequent MI; and Grace et al
      • Grace S.L.
      • Midence L.
      • Oh P.
      • et al.
      Cardiac rehabilitation program adherence and functional capacity among women: a randomized controlled trial.
      compare different models of CR in terms of their relative utility for women. Although each study is distinctive regarding the study population, methods, and themes, they coalesce as a CR triumvirate to showcase the value of CR in the broader scope of CV care. They also convey an overarching message regarding the importance of research as a means to highlight and enrich the impact of CR combined with other components of CV care.
      When it was first initiated, CR was primarily conceptualized as an exercise training (ET) and surveillance program for patients with acute MI.
      • Wenger N.K.
      Cardiac inpatient conditioning program.
      In subsequent years, it has evolved into a multifaceted secondary prevention program for a broader cross-section of patients with coronary heart disease and for patients with systolic heart failure, valvular heart disease, and HTx.
      • Dalal H.M.
      • Doherty P.
      • Taylor R.S.
      Cardiac rehabilitation.
      Moreover, the scope of CR has expanded from ET to include lifelong fitness, education, behavior change, diet modification, stress reduction, medication adherence, and overall self-sufficiency. Many believe that CR should continue to expand to serve an even wider spectrum of patients with CV who will certainly benefit (eg, patients with heart failure with preserved ejection fraction
      • Forman D.E.
      • Sanderson B.K.
      • Josephson R.A.
      • Raikhelkar J.
      • Bittner V.
      Heart failure as a newly approved diagnosis for cardiac rehabilitation: challenges and opportunities.
      ) and to even advance as a program of primary prevention
      • Arena R.
      • Lavie C.J.
      • Cahalin L.P.
      • et al.
      Transforming cardiac rehabilitation into broad-based healthy lifestyle programs to combat noncommunicable disease.
      (especially for patients with CV risk factors or evidence of subclinical disease). Given the breadth of CR's evolving curriculum, applications, and growth, it is not surprising that the 3 studies in Mayo Clinic Proceedings, and studies regarding CR in general, are quite diverse.
      Although standardized CR performance measures have been established,
      • Thomas R.J.
      • King M.
      • Lui K.
      • et al.
      AACVPR/ACC/AHA 2007 performance measures on cardiac rehabilitation for referral to and delivery of cardiac rehabilitation/secondary prevention services.
      how these are incorporated into different programs (length, format, etc) varies considerably, especially in those comparing hospital- vs home-based delivery. Such discrepancies pertain not only to the 3 articles on which this editorial is based but also occur throughout the CR literature. Even in these 3 back-to-back articles, it is hard to compare the programs with one another.
      Rosenbaum et al
      • Rosenbaum A.N.
      • Kremers W.K.
      • Schriger J.A.
      • et al.
      Association between early cardiac rehabilitation and long-term survival in cardiac transplant recipients.
      completed a nonrandomized retrospective study of 201 HTx patients older than 13 years who were urged to attend CR after their HTx during a 90-day period in which they were required to remain in the vicinity of Mayo Clinic. The study reports the association of early CR with long-term survival, and it concludes that the comprehensive ET/education/stress-reducing CR curriculum imparts vital therapeutic value. The mean ± SD number of CR sessions attended was 14±8, which is far lower than standard CR programs, yet attending 8 or more sessions was associated with survival, with incrementally greater survival for each session beyond 8.
      The nonrandomized design of the study continues a long pattern in which few randomized controlled trials (RCTs) for CR have been completed.
      • Sandesara P.B.
      • Lambert C.T.
      • Gordon N.F.
      • et al.
      Cardiac rehabilitation and risk reduction: time to “rebrand and reinvigorate.”.
      • Forman D.E.
      • Sanderson B.K.
      • Josephson R.A.
      • Raikhelkar J.
      • Bittner V.
      Heart failure as a newly approved diagnosis for cardiac rehabilitation: challenges and opportunities.
      Selection bias is likely among those who do enroll, and many confounders seem likely. Therefore, it is notable that higher pretransplant 6-minute walking distance also predicted survival, a capacity that raises the possibility that differences in debility (ie, lower debility is suggested by higher 6-minute walking distance) may have factored into some of the survival benefits attributed to CR. Appropriately, the investigators adjusted for walking speed in their assessments of CR mortality benefits. Nonetheless, higher post-HTx body mass index was also associated with survival, and this too is consistent with the possibility that survival attributed to CR may have been additionally influenced by body composition. The so-called obesity paradox in patients with heart failure may relate to greater muscle mass and related health benefits (eg, greater resiliency).
      • Lavie C.J.
      • De Schutter A.
      • Patel D.A.
      • et al.
      Body composition and survival in stable coronary heart disease: impact of lean mass index and body fat in the “obesity paradox.”.
      Diet, sleep, and other confounders may also be pertinent, but these were not considered in this study.
      Shaya et al
      • Shaya G.E.
      • Al-Mallah M.H.
      • Hung R.K.
      • et al.
      High exercise capacity attenuates the risk of early mortality after a first myocardial infarction: the Henry Ford Exercise Testing (FIT) Project.
      completed a retrospective cohort study of 2061 patients with a history of MI who underwent antecedent treadmill exercise tests sometime in the 6 years before they sustained a subsequent MI. The degree of exercise capacity assessed from the stress tests corresponded to reduced early mortality after the MI. A 1–metabolic equivalent higher exercise capacity was associated with 8% to 10% reduced mortality at 28, 90, and 365 days.
      Although the data from Shaya et al
      • Shaya G.E.
      • Al-Mallah M.H.
      • Hung R.K.
      • et al.
      High exercise capacity attenuates the risk of early mortality after a first myocardial infarction: the Henry Ford Exercise Testing (FIT) Project.
      are intriguing, it becomes a conceptual leap when the authors link the association between pre-MI exercise and lower mortality rates to a rationale to initiate CR soon after MI. Although there seems little doubt that exercise capacity is beneficial before or after an MI
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      (and the study by Shaya et al lists many of the physiologic benefits attributable to physical capacity), this does not lead to the conclusion that pre-MI exercise capacity is a rationale for post-MI CR. In fact, the study by Shaya et al presents a much stronger rationale for a primary prevention ET program before a cardiac event rather than CR after it has occurred. Furthermore, just as with the study by Rosenbaum et al,
      • Rosenbaum A.N.
      • Kremers W.K.
      • Schriger J.A.
      • et al.
      Association between early cardiac rehabilitation and long-term survival in cardiac transplant recipients.
      the retrospective nonrandomized study design is a key limitation. Fitness seems to be a good thing in any case, but the utility of CR regarding early mortality after MI could be best ascertained with an RCT to minimize bias and confounders.
      Grace et al
      • Grace S.L.
      • Midence L.
      • Oh P.
      • et al.
      Cardiac rehabilitation program adherence and functional capacity among women: a randomized controlled trial.
      studied 169 women to compare the efficacy of 3 types of CR to achieve adherence and functional capacity. Supervised mixed-sex vs supervised women-only vs home-based models of CR were compared. The study stands out as an RCT and also because it starts with the premise that CR is beneficial but then boldly shifts the focus toward process of care, ie, how can CR be implemented most successfully? Moreover, the investigators addressed the important issue of underenrollment of women; poor enrollment into programs and high attrition of those who do enroll are more problematic in women relative to men. The sex discrepancy problem has essentially plagued CR since its inception, extending in part from an early (and dated) premise that CR was primarily a means to rehabilitate men with MI during the peak time in their careers. However, it has also continued over decades as women with CV disease are often relatively older than men and are burdened with different caregiving roles as well as self-image perceptions that often factor into willingness and capacity to enroll in CR.
      • Daniels K.M.
      • Arena R.
      • Lavie C.J.
      • Forman D.E.
      Cardiac rehabilitation for women across the lifespan.
      The trial by Grace et al
      • Grace S.L.
      • Midence L.
      • Oh P.
      • et al.
      Cardiac rehabilitation program adherence and functional capacity among women: a randomized controlled trial.
      concludes with several interesting findings, yet, regrettably, the most remarkable aspect of the investigation is that it remained weak in implementation and interpretability despite its extraordinary potential. The trial officially reports CR's utility to improve functional capacity (based on cardiopulmonary exercise tests) in the women who attended CR, and those in the mixed-sex CR group attained relatively higher peak oxygen consumption than those in the same-sex and home-based programs. Those in home-based CR attended a higher percentage of CR sessions, but without deriving proportionally greater functional gains. The results differ from the investigators' hypothesis that women in the same-sex and home-based formats would derive relatively greater patient-centered support and reinforcement to enable superior functional benefits.
      However, the summation does not adequately portray relevant trial intricacies. In fact, 11.8% of participants did not attend any CR even after they were enrolled, 4.1% attended only the intake and then stopped, and 25.4% attended a different model than the one to which they were assigned. Moreover, of those who enrolled, only 53.3% completed their programs, and of those who completed, only 68.9% underwent post-CR cardiopulmonary exercise tests. These caveats leave one with the disconcerting perspective that even an RCT's conclusions regarding improved function from CR and relatively greater functional gains derived in mixed-sex formats are nebulous at best, with near certain selection and retention bias. Adding still another layer of ambiguity, evaluation of adherence to the home-based program relied solely on telephone calls; the investigators acknowledge uncertainty as to whether this truly measured improved participation, especially given the lack of improvements in exercise performance.
      Standing back from the 3 Mayo Clinic Proceedings publications, there are positive and negative messages to impart. On the negative side, each study has limitations in methods and data quality that are compounded by ambiguity in how CR is described (both regarding the format of individual sessions and the concept of minimum dose effect). However, on the positive side, there is an overwhelming signal of CR's benefits; cumulatively, the studies indicate CR's mortality, morbidity, functional, and qualitative benefits. Therefore, the limits of the studies are not reasons to criticize or delay but to forge ahead in a vital area of research with increased vigor, ie, more cognizant of potential limitations, but then implicitly more able to transcend them.
      • Balady G.J.
      • Ades P.A.
      • Bittner V.A.
      • et al.
      Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association.
      Contemporary health care challenges provide strong rationale to continue to study CR. Future research should consider expanded models of CR that address a wider spectrum of patients at a wider spectrum of times and should focus on therapeutic interventions that might enhance aggregate health as well as specific therapeutic outcomes.
      • O'Keefe J.H.
      • Franklin B.
      • Lavie C.J.
      Exercising for health and longevity vs peak performance: different regimens for different goals.
      • Franklin B.A.
      • Lavie C.J.
      • Squires R.W.
      • Milani R.V.
      Exercise-based cardiac rehabilitation and improvements in cardiorespiratory fitness: implications regarding patient benefit.
      The limitations of the trial by Grace et al
      • Grace S.L.
      • Midence L.
      • Oh P.
      • et al.
      Cardiac rehabilitation program adherence and functional capacity among women: a randomized controlled trial.
      provide a particularly important perspective regarding the challenging and complicated dimensions of behavior that can affect trials and health in general, especially behaviors pertaining to exercise and self-care. These shortcomings of enrollment and results were similar to those of HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), ie, an RCT that was intended to definitively analyze the utility of aerobic training for systolic heart failure but that was significantly and unexpectedly influenced by poor enrollment and adherence.
      • Forman D.E.
      • Sanderson B.K.
      • Josephson R.A.
      • Raikhelkar J.
      • Bittner V.
      Heart failure as a newly approved diagnosis for cardiac rehabilitation: challenges and opportunities.
      One can try to refine RCTs to be as rigorous as possible, but methods may still progress in unexpected directions. These complexities also highlight the utility of comprehensive registry data with meticulous methods to address confounders (eg, propensity score analyses) as important complementary research priorities.
      • Niebauer J.
      • Mayr K.
      • Harpf H.
      • et al.
      Long-term effects of outpatient cardiac rehabilitation in Austria: a nationwide registry.

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