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Canadian Journal of Cardiology

Failing at Heart Failure Therapies: Are Health Behaviours to Blame?

Published:September 01, 2017DOI:https://doi.org/10.1016/j.cjca.2017.08.021
      The challenge of health behaviour improvements is not that they do not work to reduce the risk of adverse events associated with cardiovascular disease (CVD); they do.
      • Martin B.J.
      • Arena R.
      • Haykowski M.
      • et al.
      Cardiovascular fitness and mortality following contemporary cardiac rehabilitation.
      Rather, the true challenge is that most of contemporary society simply finds it virtually impossible to continually emulate a healthy living phenotype, although small positive changes in health behaviours, when the levels of those behaviours are less than ideal, can be highly beneficial.
      • Folsom A.R.
      • Yatsuya H.
      • Nettleton J.A.
      • et al.
      Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence.
      • Younus A.
      • Aneni E.C.
      • Spatz E.S.
      • et al.
      A systematic review of the prevalence and outcomes of ideal cardiovascular health in US and non-US populations.
      For example, moving more by any approach (sitting less and taking more steps throughout the day as well as participating in structured exercise programs on any level), portends tremendous health benefits.

      Arena R, McNeil A, Street S, et al. Let us talk about moving: reframing the exercise and physical activity discussion. Curr Probl Cardiol, in press. doi:10.1016/j.cpcardiol.2017.06.002.

      The real struggle in getting people to change their health behaviours is not in trying to convince them that they need to make major changes, but in trying to help them understand why they need to change and how little they need to do to improve their longevity and significantly increase their event-free survival.
      • Folsom A.R.
      • Yatsuya H.
      • Nettleton J.A.
      • et al.
      Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence.
      • Wannamethee S.G.
      • Shaper A.G.
      • Walker M.
      Changes in physical activity, mortality, and incidence of coronary heart disease in older men.
      In his book, Man's Search for Meaning, Victor Frankl, a psychiatrist, describes his experiences trying to survive the Nazi work camps in World War II.
      • Frankl V.E.
      Man's Search for Meaning; An Introduction to Logotherapy.
      His seminal observation was that those who survived were rarely the strongest, the youngest, or the fittest. They were the men who had a reason to live. His summary phrase as to how people can successfully change their behaviour and improve their outlook was, “If they have a why, they will find the how.” And yet all too often in contemporary acute care-based, procedural-biased health care, we have little or no opportunity to help our patients understand their “personal healthy living why” so they themselves can determine their “how.” To be sure, personal empowerment and self-efficacy are critical if patients are to possess the confidence to make meaningful and sustainable changes.
      • Bandura A.
      Self-efficacy: toward a unifying theory of behavioral change.
      However, if we, as health care professionals, learn to focus on helping our patients understand why they need to change their health behaviours, then the wealth of knowledge and experience that we possess will be much more readily received and engrained as we coach them on how change can be achieved.
      One of the most challenging health behaviour changes to get people to embrace is daily physical activity and regular exercise. Most North Americans simply do not understand why they need to engage in regular physical activity and have thus never thought about how they might achieve that goal. In fairness, all too often we, as health care professionals, set the physical activity and exercise bars far too high for most of the population to even begin to contemplate achieving. An additional barrier to improving the physical and mental health of our patients through physical activity and exercise is the reality that some health care professionals, physicians in particular, choose to ignore the virtual tsunami of data supporting the positive effects of exercise training in reducing major adverse cardiac events (MACE) in CVD patients by stating unequivocally that some reasonably large randomized clinical trials of cardiac rehabilitation and exercise training in CVD patients have shown lackluster results. Two trials in particular come to mind. These are the Rehabilitation After Myocardial Infarction Trial (RAMIT), and Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trials.
      • West R.R.
      • Jones D.A.
      • Henderson A.H.
      Rehabilitation after myocardial infarction trial (RAMIT).
      • O'Conner C.M.
      • Whellan D.J.
      • Lee K.L.
      • et al.
      Efficacy and safety of exercise training in patients with chronic heart failure.
      Each of these trials failed to show the hypothesized positive effect of exercise on decreasing the rate of adverse CVD events, and the health behaviour naysayers hold these up as proof-positive that we should not be wasting money on interventions such as cardiac rehabilitation or exercise training. However, rather than simply stating that these trials failed and exercise training or cardiac rehabilitation is useless, it is critically important to understand why they failed, if indeed they did. This explanation is particularly germane to any discussion of the role of exercise training in improving outcomes for CVD patients, and heart failure (HF) patients in particular.
      In RAMIT, after 1 year of follow-up, there were significantly fewer cardiac rehabilitation subjects still exercising compared with control subjects.
      • West R.R.
      • Jones D.A.
      • Henderson A.H.
      Rehabilitation after myocardial infarction trial (RAMIT).
      After 2 years of follow-up, there were no effects on mortality in either group. The study investigators concluded that cardiac rehabilitation was not effective in reducing mortality despite their own data showing that most intervention study subjects did not exercise the intervention. The HF-ACTION was a 3-year randomized trial of exercise training vs usual care to reduce MACE in patients with a history of HF with reduced ejection fraction (HFREF; left ventricular [LV] ejection fraction < 35%).
      • O'Conner C.M.
      • Whellan D.J.
      • Lee K.L.
      • et al.
      Efficacy and safety of exercise training in patients with chronic heart failure.
      In this clinical trial, < 70% of the intervention subjects actually completed all of the exercise sessions. Of even greater relevance with respect to the efficacy of exercise training in reducing MACE in HFREF patients, on average only 25% of the subjects in the exercise treatment arm reported they were still exercising 2 years into the trial and, in the unlikely event they were still exercising, they were only doing approximately 10 minutes per day. It would be very difficult to imagine that a clinical trial of a pharmacological intervention, in which 25% of the active treatment subjects received a subtherapeutic dose of the study drug, would see a clinical benefit. The real story in each of these trials is not that the health behaviour interventions did not work. To the contrary, persons who did adhere to these interventions had significant benefits.
      • Keteyian S.J.
      • Leifer E.S.
      • Houston-Miller N.
      • et al.
      Relation between volume of exercise and clinical outcomes in patients with heart failure.
      The real story is that health behaviour interventions, just like drugs that are not taken or interventions that are not performed, do not work when they are not adopted and maintained. They do work, and very well, when they are adopted and adhered to.
      • Arena R.
      • Lavie C.J.
      Preventing bad and expensive things from happening by taking the healthy living polypill: everyone needs this medicine.
      With the purportedly disappointing results of the HF-ACTION study regarding the apparent lack of benefit of exercise in reducing subsequent cardiac events in patients with HFREF, many hospital-based specialists, and community practitioners, have become reluctant to refer these patients for cardiac rehabilitation. However, for the reasons outlined previously, when successfully applied, increasing physical activity and exercise does work to reduce MACE in HFREF patients.
      • Keteyian S.J.
      • Leifer E.S.
      • Houston-Miller N.
      • et al.
      Relation between volume of exercise and clinical outcomes in patients with heart failure.
      However, with a rapidly aging population worldwide, the emergence of HF with preserved ejection fraction (HFPEF) as a clinically and epidemiologically important entity, perhaps the most relevant clinical question in HF and exercise training in the decades to come is not whether increasing physical activity and exercise is beneficial in HFREF populations, but whether it can be extended to those with HFPEF.
      In this issue, Yavari and colleagues performed a cross-sectional observational study in 4 groups of patients: (1) a healthy control group; (2) an at-risk group for HF with preserved LV function but with 1 or more of hypertension, diabetes mellitus, atrial fibrillation, obesity, documented symptomatic coronary artery disease, or chronic obstructive pulmonary disease; (3) symptomatic patients with HFPEF; and (4) symptomatic patients with HFREF (LV ejection fraction < 45%).
      • Yavari M.
      • Haykowsky M.J.F.
      • Savu A.
      • et al.
      Volume and patterns of physical activity across the health and heart failure continuum.
      The participants all wore an accelerometer that was used to assessed daily energy expenditure, physical activity energy expenditure, daily step counts, and time spent in different intensities of physical activity (ie, light, moderate, or vigorous) and sedentary time. Importantly, for the results of this study, a bout of physical activity had to meet 2 criteria: (1) it started and ended with a minute of activity performed at > 3 metabolic equivalents; and (2) it was > 10 minutes in duration with no more than 2 minutes of activity < 3 metabolic equivalents during that exercise bout.
      The authors determined that daily energy expenditure and sedentary times were not significantly different between the 4 groups. Sedentary times accounted for 66% percent of waking time across the 4 groups but in both HF groups it was up to 79% of waking time. With respect to physical activity and steps per day, the control group was the most active, followed by the at-risk group. Perhaps not surprisingly, the HFREF and the HFPEF groups were the least active. However, somewhat unexpectedly, the HFPEF group was significantly less active than the HFREF group in terms of steps taken per day as well as in the in the amount of time they spent in physical activity.
      When it comes to physical activity and HF populations, most clinicians would likely answer they would expect the HFREF group to be less active than the HFPEF. However, in this study, it was the polar opposite. The first question that comes to mind is whether this is a spurious finding, which might not be repeated in follow-up studies. However, the authors carefully and objectively documented levels of physical activity, so this seems unlikely. What is truly interesting, and potentially provocative about this observation, is the emerging link between the role of systemic or vascular inflammation in regulating fibrosis, the generation of myocyte fibrosis leading to atrial fibrillation, or diastolic dysfunction and HFPEF, and the potential benefits of regular physical activity and exercise training in reducing inflammation as well as HFPEF.
      • Hartupee J.
      • Man D.L.
      Role of inflammatory cells in fibroblast activation.
      • Dzeshka M.S.
      • Lip G.Y.
      • Snezhitskly V.
      • Shantsila E.
      Cardiac fibrosis in patients with atrial fibrillation: mechanisms and implications.
      • Fedewa M.V.
      • Hathaway E.D.
      • Ward-Ritacco C.L.
      Effect if exercise training on C-reactive protein: a systematic review and meta-analysis of randomized and non-randomized controlled trials.
      The observation by Yavari and colleagues, that HFPEF patients are very sedentary and physically inactive, certainly suggests that the systemic and vascular inflammation attendant with these unhealthy behaviours, might indeed play an etiological role in the generation of HFPEF.
      • Yavari M.
      • Haykowsky M.J.F.
      • Savu A.
      • et al.
      Volume and patterns of physical activity across the health and heart failure continuum.
      The uncompensated production of free oxygen species, as a direct consequence of unbalanced caloric metabolism (too many calories ingested with insufficient caloric output to safely metabolize them), that leads to inflammation might play a causal role in cellular apoptosis and the generation of atrial and ventricular myocyte fibrosis frequently observed in atrial fibrillation and ventricular diastolic dysfunction.
      • Dzeshka M.S.
      • Lip G.Y.
      • Snezhitskly V.
      • Shantsila E.
      Cardiac fibrosis in patients with atrial fibrillation: mechanisms and implications.
      • Moreo A.
      • Ambrosio G.
      • De Chiara B.
      • et al.
      Influence of myocardial fibrosis on left ventricular diastolic dysfunction. Noninvasive assessment by cardiac magnetic resonance and echo.
      Again, because of the aging population and the increasing prevalence of atrial fibrillation, ventricular diastolic dysfunction, and HFPEF, this possibility definitely merits further investigation.
      Yavari and coworkers have certainly produced a very interesting clinical observation that might constitute a significant watershed with respect to furthering our understanding of the associations among sedentary behaviour, inflammation, myocardial fibrosis, atrial fibrillation, diastolic dysfunction, and HFPEF. Whether exercise training and cardiac rehabilitation can successfully treat HFPEF patients, or even potentially prevent the development of HFPEF, remains to be determined. In particular, whether some forms of physical activity and exercise training, such as high-intensity interval training, are more beneficial than moderate-intensity training in preventing or treating HFPEF needs to be established.
      • Palau P.
      • Nüñez E.
      • Dominguez E.
      • et al.
      Physical therapy in heart failure with preserved ejection fraction: a systematic review.
      In addition, the distinct possibility that too much vigorous aerobic exercise can lead to systemic or vascular inflammation, causing myocyte fibrosis, and atrial or even ventricular fibrillation needs to be investigated.
      • O'Keefe J.H.
      • Lavie C.J.
      Run for your life, at a comfortable speed and not too far.
      If health care professionals are to confidently prescribe exercise therapies for HF patients, or any other patients or populations, we need a much better understanding of the boundaries of therapeutic doses vs potentially lethal doses. After all, in the challenging clinical practice environment of successfully motivating patients, and the population in general, to find the required “why” they need to change and the “how” they will accomplish it, the one impediment we must void is even the slightest notion that healthy behaviours can potentially be deadly behaviours. If that were to transpire, we would fail at far more than treating HF patients. We would fail at engraining our children and youth with the health behaviours that have been shown to improve quality of life and significantly reduce the clinical and socioeconomic effects of a myriad of chronic diseases.

      Disclosures

      The authors have no conflicts of interest to disclose.

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