EXERCISE INTOLERANCE IN CHRONIC HEART FAILURE: MECHANISMS AND THERAPIES. PART II
Piepola MF, Guazzic M, Borianid G, Cicoirae M, Corra U, et al, on behalf of the Working Group "Exercise Physiology, Sport Cardiology and Cardiac Rehabilitation" of the Italian Society of Cardiology (Italian Federation of Cardiology)
Eur J Cardiovasc Prev Rehabil. 2010;17(6):637-648. doi:10.1097/HJR.0b013e3283361dc5.
Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multi-organ failure present in this syndrome must be highlighted. We aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in the symptom generation. In the first part of the review, six key factors were revised (the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium). In this second part, the role of the excitatory reflexes and the cardiac cachexia are presented. Finally, potential therapeutic implications are discussed here. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.
STAIRS INSTEAD OF ELEVATORS AT WORKPLACE: CARDIOPROTECTIVE EFFECTS OF A PRAGMATIC INTERVENTION
Meyer P, Kayser B, Kossovsky M, Sigaud P, Carballo D, et al
Eur J Cardiovasc Prev Rehabil. 2010;17(5):569-575; doi: 10.1097/HJR.0b013e328338a4dd
Background:
Population strategies to increase physical activity are an essential part of cardiovascular disease prevention. However, little data exist on lifestyle interventions that are easy to integrate into everyday life such as using stairs instead of elevators at the workplace.
Design:
Pre and post-intervention study.
Methods:
A 12-week promotional campaign for stair use consisting of posters and floor stickers at the point of choice between stairs and elevators at each hospital floor was organized in a university hospital building. In 77 selected employees with an inactive lifestyle, physical activity, aerobic fitness, anthropometrics, blood pressure, lipids, insulin sensitivity, and C-reactive protein were assessed at baseline, 12 weeks, and 6 months.
Results:
During the intervention, median daily number of ascended and descended one-story staircase units was 20.6/day (14.2-28.1) compared with 4.5/day (1.8-7.2) at baseline (P < 0.001). At 12 weeks, estimated maximal aerobic capacity had increased by 9.2 +/- 15.1% (P < 0.001) corresponding with approximately 1 MET. There were significant declines in waist circumference (-1.7 +/- 2.9%), weight (-0.7 +/- 2.6%), fat mass (-1.5 +/- 8.4%), diastolic blood pressure (-1.8 +/- 8.9%), and low-density lipoprotein cholesterol (-3.0 +/- 13.5%). At 6 months, the median daily number of ascended and descended one-story staircase units had decreased to 7.2 (3.5-14.0). Benefits on estimated maximal aerobic capacity (+5.9 +/- 12.2%, P = 0.001) and fat mass (-1.4 +/- 8.4%, P = 0.038) persisted.
Conclusion:
Encouraging stair use at work is effective for improving fitness, body composition, blood pressure, and lipid profile in asymptomatic individuals with an inactive lifestyle and thus may be a simple way to significantly reduce cardiovascular disease risk at the population level.
Editor's Comment.
Two very different articles are presented for your interest this issue. Piepola et al, on behalf of a large working group (Italian Society of Cardiology-Italian Federation of Cardiology), have written an excellent, two-part review of exercise in heart failure patients for the European Journal of Cardiovascular Prevention and Rehabilitation. The second article, by Meyer and colleagues (in the same journal), touches on an issue that we've presented previously in this column, physical activity, but is interesting in its approach and design, as well as the outcomes.
Piepola et al's review articles are well written and well organized. They present a complex subject in a straightforward and clear, though somewhat complicated, manner. Part I of the series discusses the role of the heart, lung, skeletal muscle, hormonal changes, oxygen delivery to the periphery, and the endothelium in chronic, congestive heart failure. It summarizes the known literature relevant to heart failure and connects it to exercise. Part II discusses excitatory reflexes (ie, increased sympathetic nervous system drive and activity) and cardiac cachexia (myocardial atrophy), and therapeutic modalities are discussed. The summaries presented in each of these areas are relatively complete and provide excellent citations to the research literature for those who might wish to read more. The discussion of each area is tied to symptoms, physiology of chronic heart failure (CHF), patient management, and as stated above, the therapeutic issues and modalities for treating CHF. I highly recommend these articles for practicing professionals who need to upgrade their knowledge in heart failure, which is proceeding at break-neck speed in the literature. This writing group is an obvious advocate for exercise in CHF patients and it emerges in this series.
The article by Meyer et al is interesting in a number of ways. It presents an "intervention" for increasing physical activity (PA) in an inactive population. In the last Literature Update column (November/December, 2010), 3 articles on "sedentary behavior" were presented. My goal for that column was for professionals to emphasize the importance of increasing physical activity and decreasing sedentary time as part of an active, healthy lifestyle. Assisting patients to increase daily PA and decrease daily sedentary (sitting) time is an important addition to the repertoire of the cardiac rehabilitation professional. This current study, published in the European Journal of Cardiovascular Prevention and Rehabilitation, demonstrates the effectiveness of a relatively minor (and simple) change in PA. Meyer et al call it a "pragmatic" intervention; indeed it is. They recruited 77 inactive hospital employees and simply asked them to walk stairs rather than taking the elevator at work. Signs were posted in the facility at the "decision point" between the elevator and the stairs. The average daily excursion of stairs increased from 4.5 flights per day to 20.6 per day after 12 weeks of the intervention (P < .001). Significant changes (P < .05 in all cases) in estimated maximal oxygen uptake, body weight, waist circumference, diastolic blood pressure, triglycerides, and LDL cholesterol were demonstrated in the intervention group by the end of the 12-week experimental period. These results, from a relatively simple and minor change in daily routine (Meyer et al state that the increased stair climbing is equivalent to "10 minutes of daily exercise") resulted in significant changes in cardiovascular risk factors. This is, or should be, exciting to cardiac rehabilitation professionals-invoke a small, relatively simple change in daily PA and reap large benefits. The authors followed up on the participants after 6 months to determine the permanency of the stair climbing as well as the physiological changes. Unfortunately, the flights climbed per day had decreased from 20.6 to 7.2; although this was significantly lower than the 12-week value, it remained significantly higher than the original 4.5 flights per day. Lessons to be taken from this are relatively clear: (1) it is not all that complicated to find ways to increase daily PA, (2) apparently it is not that difficult to actually make those changes, and (3) the increased PA is worth the effort. The last take-away lesson is that the new behavior can (and probably will) be extinguished quickly unless there is sufficient support in the environment for continued PA. Although the study has its limitations, it is a good example of the simplicity and the effectiveness of increasing daily PA.
-JLR
EXERCISE INDUCED SKELETAL MUSCLE METABOLIC STRESS IS REDUCED AFTER PULMONARY REHABILITATION IN COPD
Calvert LD, Singh SJ, Morgan MD, Steiner MC
Respir Med. Published online first October 30, 2010; doi:10.1016/j.rmed.2010.10.012
Summary:
In COPD, skeletal muscle ATP resynthesis may be insufficient to meet demand during exercise due to excessive anaerobic and reduced oxidative (mitochondrial) energy production, leading to metabolic stress. We investigated the effect of outpatient pulmonary rehabilitation (PR) on the metabolic response (measured by exercise-induced accumulation of plasma ammonia) and determined whether this response predicted functional improvement following PR. 25 subjects with stable COPD [mean (SD) age 67 (8)years and FEV1 47 (18)% predicted] performed maximal cycling ergometry before and after PR. Plasma ammonia was measured at rest, during exercise and 2 min post-exercise. Following PR, there were significant increases in peak cycle WR and ISWT performance (Mean (SEM) changes 13.1 (2.0) W and 93 (15) m respectively, p < 0.001). Mean (SEM) rise in plasma ammonia was reduced at peak (Pre vs Post-PR: 29.0 (4.5) vs 20.2 (2.5) mmol/l, p < 0.05) and isotime (Pre vs Post-PR: 29.0 (4.5) vs 10.6 (1.7) mmol/l, p < 0.001) exercise. Improvements in exercise performance after PR were similar among subgroups who did versus those who did not show a rise in ammonia at baseline. The results suggest that muscle cellular energy production was better matched to the demands of exercise following PR. We conclude that a pragmatic outpatient PR programme involving high intensity walking exercise results in significant adaptation of the skeletal muscle metabolic response with a reduction in exercise-related metabolic stress. However, the outcome of PR could not be predicted from baseline metabolic response.
Editor's Comment.
This is an interesting study of entirely unclear significance. The investigators start with the premise that the rise in blood ammonia level in response to exercise is a measure of metabolic stress in muscle, based on both healthy volunteer studies as well as their own data from patients with chronic obstructive pulmonary disease (COPD). However, they also note that some patients (7 out of the 25 patients in this study) do not show such a response; whether this reflects lower metabolic stress or is a function of other undefined mechanisms is unknown. The study reports that the remaining 18 showed a decrease in the magnitude of the ammonia rise after pulmonary rehabilitation, and this is taken as an indicator of metabolic stress reduction as a beneficial effect of exercise training. There was no difference in the exercise improvement between the 2 groups (with or without an increase in ammonia levels with exercise prerehabilitation), and there was no other robust measure of muscle abnormality, histological or histochemical, to place the blood ammonia levels in context. Until those types of data are available, this will remain an interesting study of entirely unclear significance.
-SK
BECLOMETHASONE/FORMOTEROL IN THE MANAGEMENT OF COPD: A RANDOMISED CONTROLLED TRIAL
Calverley PMA, Kuna P, Monso E, Costantini M, Petruzzelli S, et al
Respir Med. Published online first October 20, 2010; doi:10.1016/j.rmed.2010.09.008
Objectives:
To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol (non-inferiority) and versus formoterol (superiority) in patients with severe stable chronic obstructive pulmonary disease (COPD).
Methods:
A double-blind, double-dummy, randomised, active-controlled, parallel-group study. After 4 weeks run-in with ipratropium/salbutamol (40/200 [mu]g, three times daily) patients were randomised to receive beclomethasone/formoterol (200/12 [mu]g pressurised metered dose inhaler), budesonide/formoterol (400/12 [mu]g dry powder inhaler) or formoterol (12 [mu]g dry powder inhaler) twice daily for 48 weeks. Co-primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1s (FEV1) and mean rate of COPD exacerbations.
Results:
Of 718 patients randomised, 703 (232 beclomethasone/formoterol, 238 budesonide/formoterol, 233 formoterol) were in the ITT analysis. Improvement in pre-dose morning FEV1 was 0.077 L, 0.080 L and 0.026 L for beclomethasone/formoterol, budesonide/formoterol and formoterol respectively (LS mean from the ANCOVA model). Beclomethasone/formoterol was not inferior to budesonide/formoterol (95% CI of the difference -0.052, 0.048) and superior to formoterol (p = 0.046). The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments (beclomethasone/formoterol 0.414, budesonide/formoterol 0.423 and formoterol 0.431). Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased. Safety profiles were as expected and treatments well-tolerated.
Conclusions:
Beclomethasone/formoterol (400/24 [mu]g) treatment for 48 weeks improved pulmonary function, reduced symptoms compared to formoterol, was safe and well-tolerated in patients with severe stable COPD. Neither of the long-acting [beta]2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population.
Editor's Comment.
In the interval between conventional therapies of the present and the promised biological agent-driven miracles in the future, the pace is somewhat slow in the world of airway disease therapies. That should explain "me-too" studies such as this one, which reinvents the inhaled corticosteroid (ICS) beclomethasone in a more bioavailable form and pits it against its younger sibling, budesonide, with both being combined with the long-acting [beta]2 agonist (LABA), formoterol, in patients with moderate to severe COPD (FEV1 between 30% and 50% of predicted).
Both arms come out equal in their effects on predose FEV1 after 48 weeks and superior to formoterol alone. Equivalent benefits were seen in quality of life measures and rescue inhaler use. The acute exacerbation rate was already low and remained lower than expected in all the treatment arms. The side effect profiles were "as expected" and largely the same between the groups. Unless the beclomethasone/formoterol combination is significantly cheaper than the similar ICS/LABA combinations already available, there seems no other advantage to justify its existence from a user perspective. This may not prevent its entry into the market, but in these lean times, its mere availability may not be a good enough reason to actually prescribe it.
-SK