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Pathophysiology of Exercise Intolerance and Its Treatment With Exercise-Based Cardiac Rehabilitation in Heart Failure With Preserved Ejection Fraction.
Tucker, WJ, Angadi, SS, Haykowsky, MJ, Nelson, MD, Sarma, S, Tomczak, CR
Journal of cardiopulmonary rehabilitation and prevention. 2020;(1):9-16
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Abstract
Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of heart failure in the United States. The cardinal feature of HFpEF is reduced exercise tolerance (peak oxygen uptake, (Equation is included in full-text article.)O2peak) secondary to impaired cardiac, vascular, and skeletal muscle function. There are currently no evidence-based drug therapies to improve clinical outcomes in patients with HFpEF. In contrast, exercise training is a proven effective intervention for improving (Equation is included in full-text article.)O2peak, aerobic endurance, and quality of life in HFpEF patients. This brief review discusses the pathophysiology of exercise intolerance and the role of exercise training to improve (Equation is included in full-text article.)O2peak in clinically stable HFpEF patients. It also discusses the mechanisms responsible for the exercise training-mediated improvements in (Equation is included in full-text article.)O2peak in HFpEF. Finally, it provides evidence-based exercise prescription guidelines for cardiac rehabilitation specialists to assist them with safely implementing exercise-based cardiac rehabilitation programs for HFpEF patients.
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Type 2 diabetes and reduced exercise tolerance: a review of the literature through an integrated physiology approach.
Nesti, L, Pugliese, NR, Sciuto, P, Natali, A
Cardiovascular diabetology. 2020;(1):134
Abstract
The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) is well established. Early in the course of the diabetic disease, some degree of impaired exercise capacity (a powerful marker of health status with prognostic value) can be frequently highlighted in otherwise asymptomatic T2DM subjects. However, the literature is quite heterogeneous, and the underlying pathophysiologic mechanisms are far from clear. Imaging-cardiopulmonary exercise testing (CPET) is a non-invasive, provocative test providing a multi-variable assessment of pulmonary, cardiovascular, muscular, and cellular oxidative systems during exercise, capable of offering unique integrated pathophysiological information. With this review we aimed at defying the cardiorespiratory alterations revealed through imaging-CPET that appear specific of T2DM subjects without overt cardiovascular or pulmonary disease. In synthesis, there is compelling evidence indicating a reduction of peak workload, peak oxygen assumption, oxygen pulse, as well as ventilatory efficiency. On the contrary, evidence remains inconclusive about reduced peripheral oxygen extraction, impaired heart rate adjustment, and lower anaerobic threshold, compared to non-diabetic subjects. Based on the multiparametric evaluation provided by imaging-CPET, a dissection and a hierarchy of the underlying mechanisms can be obtained. Here we propose four possible integrated pathophysiological mechanisms, namely myocardiogenic, myogenic, vasculogenic and neurogenic. While each hypothesis alone can potentially explain the majority of the CPET alterations observed, seemingly different combinations exist in any given subject. Finally, a discussion on the effects -and on the physiological mechanisms-of physical activity and exercise training on oxygen uptake in T2DM subjects is also offered. The understanding of the early alterations in the cardiopulmonary response that are specific of T2DM would allow the early identification of those at a higher risk of developing HF and possibly help to understand the pathophysiological link between T2DM and HF.
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Dietary nitrate's effects on exercise performance in heart failure with reduced ejection fraction (HFrEF).
Mulkareddy, V, Racette, SB, Coggan, AR, Peterson, LR
Biochimica et biophysica acta. Molecular basis of disease. 2019;(4):735-740
Abstract
Heart failure with reduced ejection fraction (HFrEF) is a deadly and disabling disease. A key derangement contributing to impaired exercise performance in HFrEF is decreased nitric oxide (NO) bioavailability. Scientists recently discovered the inorganic nitrate pathway for increasing NO. This has advantages over organic nitrates and NO synthase production of NO. Small studies using beetroot juice as a source of inorganic nitrate demonstrate its power to improve exercise performance in HFrEF. A larger-scale trial is now underway to determine if inorganic nitrate may be a new arrow for physicians' quiver of HFrEF treatments.
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Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond.
Tschöpe, C, Kherad, B, Klein, O, Lipp, A, Blaschke, F, Gutterman, D, Burkhoff, D, Hamdani, N, Spillmann, F, Van Linthout, S
European journal of heart failure. 2019;(1):14-22
Abstract
Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs.
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Exercise capacity, physical activity, and morbidity.
Brunjes, DL, Kennel, PJ, Christian Schulze, P
Heart failure reviews. 2017;(2):133-139
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Abstract
Muscle weakness and atrophy are key characteristics of the aging adult but can also be found in chronically ill patients with heart failure, cancer, renal failure, and chronic infectious diseases all associated with an accelerated level of muscle dysfunction. Reduced physical activity levels and exercise intolerance increase muscle loss and decrease quality of life in both the aging and heart failure populations. The purpose of this review is to provide an overview of the effects of aging and heart failure on skeletal muscle function and how exercise training can improve long-term outcomes associated with skeletal muscle dysfunction.
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An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease.
Maltais, F, Decramer, M, Casaburi, R, Barreiro, E, Burelle, Y, Debigaré, R, Dekhuijzen, PN, Franssen, F, Gayan-Ramirez, G, Gea, J, et al
American journal of respiratory and critical care medicine. 2014;(9):e15-62
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Abstract
BACKGROUND Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. PURPOSE The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. METHODS An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. RESULTS We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. CONCLUSIONS Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.
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Reporting of exercise attendance rates for people with chronic obstructive pulmonary disease: a systematic review.
Williams, MT, Lewis, LK, McKeough, Z, Holland, AE, Lee, A, McNamara, R, Phillips, A, Wiles, L, Knapman, L, Wootton, S, et al
Respirology (Carlton, Vic.). 2014;(1):30-7
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Abstract
While recommendations for the duration, frequency, mode and intensity of exercise programmes for people with chronic obstructive pulmonary disease (COPD) are specified in consensus statements, criteria for exercise session attendance are less clear. The review questions were: (i) how commonly are a priori criteria and attendance rates reported for people with COPD participating in exercise programmes and (ii) what is the strength of association between attendance and improvements in functional exercise capacity. Database searches identified primary studies of people with COPD participating in exercise or pulmonary rehabilitation programmes of at least 2 weeks duration. Primary outcomes were a priori criteria for attendance, reports of attendance at supervised exercise sessions and mean improvements in functional exercise assessments. Data extraction processes were confirmed prospectively (>80% agreement). Variants of exercise attendance data were described. Linear associations between attendance and improvements in exercise outcomes were explored (Pearson r, P < 0.05). Of the 234 included studies, 86 (37%) reported attendance and 29 (12%) provided a priori criteria for attendance. In the small sample of studies which reported attendance and functional exercise data before and after the intervention, there was little to no relationship between improvements in functional exercise capacity and training volume (prescribed r = -0.03, P = 0.88; attended r = -0.24, P = 0.18). Reporting of exercise programme attendance rates is low and of variable quality for people with COPD. Consistent and explicit reporting of exercise attendance in people with COPD will enable calculation of dose-response relationships and determine the value of a priori exercise attendance criteria.
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Six-minute walk test: a valuable tool for assessing pulmonary impairment.
Morales-Blanhir, JE, Palafox Vidal, CD, Rosas Romero, Mde J, García Castro, MM, Londoño Villegas, A, Zamboni, M
Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2011;(1):110-7
Abstract
Over the last few years, the use of exercise tests has come to be recognized as a convenient method of evaluating respiratory function, because the reserves of the various systems in the human body should be known in order to provide a more complete portrayal of the functional capacities of the patient. Because walking is one of the main activities of daily living, walk tests have been proposed in order to measure the state or the functional capacity of patients. The six-minute walk test has proven to be reproducible and is well tolerated by patients. It evaluates the distance a person can walk on a flat, rigid surface in six minutes. Its main objective is to determine exercise tolerance and oxygen saturation during submaximal exercise. In this review, we present various clinical areas in which the test can provide useful data.
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Mechanisms of exercise limitation and pulmonary rehabilitation for patients with neuromuscular disease.
Aboussouan, LS
Chronic respiratory disease. 2009;(4):231-49
Abstract
Indications for exercise and pulmonary rehabilitation extend to neuromuscular diseases tough these conditions pose particular challenges given the associated skeletal muscle impairment and respiratory muscle dysfunction. These challenges are compounded by the variety of exercise prescriptions (aerobic, muscle strengthening, and respiratory muscle training) and the variety of neuromuscular disorders (muscular, motor neuron, motor nerve root, and neuromuscular transmission disorders). Studies support a level II evidence of effectiveness (i.e., likely to be effective) for a combination of aerobic exercise and strengthening exercises in muscular disorders, and for strengthening exercises in amyotrophic lateral sclerosis. The potential deleterious effects of work overload in the dystrophinopathies have not been confirmed in Becker muscular dystrophy. Adjunctive pharmacologic interventions (e.g., theophylline, steroids, PDE5 inhibitors, creatine), training recommendations (e.g., interval or lower intensity training) and supportive techniques (e.g., noninvasive ventilation, neuromuscular electrical stimulation, and diaphragm pacing) may result in more effective training but require more study before formal recommendations can be made. The exercise prescription should include avoidance of inspiratory muscle training in hypercapnia or low vital capacity, and should match the desired outcome (e.g., extremity training for task-specific performance, exercise training to enhance exercise performance, respiratory muscle training where respiratory muscle involvement contributes to the impairment).
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Muscle fatigue during football match-play.
Reilly, T, Drust, B, Clarke, N
Sports medicine (Auckland, N.Z.). 2008;(5):357-67
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Abstract
One of the consequences of sustaining exercise for 90 minutes of football match-play is that the capability of muscle to generate force declines. This impairment is reflected in the decline of work-rate towards the late part of the game. Causes of this phenomenon, which is known as fatigue, and some of its consequences are considered in this article. The stores of muscle glycogen may be considerably reduced by the end of the game, especially if there has not been a tapering of the training load. Thermoregulatory strain may also be encountered, resulting in a fall in physical performance, or there may be a reduced central drive from the nervous system. The decline in muscle strength may increase the predisposition to injury in the lower limbs. Central fatigue may also occur with implications for muscle performance. Strategies to offset fatigue include astute use of substitutions, appropriate nutritional preparation and balancing pre-cooling and warm-up procedures. There is also a role for endurance training and for a pacing strategy that optimizes the expenditure of energy during match-play.