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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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The impact of statins on physical activity and exercise capacity: an overview of the evidence, mechanisms, and recommendations.
Schweitzer, AM, Gingrich, MA, Hawke, TJ, Rebalka, IA
European journal of applied physiology. 2020;(6):1205-1225
Abstract
PURPOSE Statins are among the most widely prescribed medications worldwide. Considered the 'gold-standard' treatment for cardiovascular disease (CVD), statins inhibit HMG-CoA reductase to ultimately reduce serum LDL-cholesterol levels. Unfortunately, the main adverse event of statin use is the development of muscle-associated problems, referred to as SAMS (statin-associated muscle symptoms). While regular moderate physical activity also decreases CVD risk, there is apprehension that physical activity may induce and/or exacerbate SAMS. While much work has gone into identifying the epidemiology of SAMS, only recent research has focused on the extent to which these muscle symptoms are accompanied by functional declines. The purpose of this review is to provide an overview of possible mechanisms underlying SAMS and summarize current evidence regarding the relationship between statin treatment, physical activity, exercise capacity, and SAMS development. METHODS PubMed and Google Scholar databases were used to search the most relevant and up-to-date peer-reviewed research on the topic. RESULTS The mechanism(s) behind SAMS, including altered mitochondrial metabolism, reduced coenzyme Q10 levels, reduced vitamin D levels, impaired calcium homeostasis, elevated extracellular glutamate, and genetic polymorphisms, still lack consensus and remain up for debate. Our summation of the evidence leads us to suggest that the etiology of SAMS development is likely multifactorial. Our review also demonstrates that there is limited evidence for statins impairing exercise adaptations or reducing exercise capacity for the majority of the investigated populations. CONCLUSION The available evidence indicates that the benefits of engaging in physical activity while on statin medication largely outweigh the risks.
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Cross-country skiing and the risk of acute myocardial infarction: A prospective cohort study.
Laukkanen, JA, Lakka, TA, Ogunjesa, BA, Kurl, S, Kunutsor, SK
European journal of preventive cardiology. 2020;(10):1108-1111
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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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The Effect of Nitrate Supplementation on Exercise Tolerance and Performance: A Systematic Review and Meta-Analysis.
Van De Walle, GP, Vukovich, MD
Journal of strength and conditioning research. 2018;(6):1796-1808
Abstract
Van De Walle, GP and Vukovich, MD. The effect of nitrate supplementation on exercise tolerance and performance: a systematic review and meta-analysis. J Strength Cond Res 32(6): 1796-1808, 2018-The purpose of this article was to systematically review the current literature and evaluate the overall efficacy of nitrate supplementation on exercise tolerance and performance by meta-analysis. Studies were eligible for inclusion if they met the following criteria: (a) were an experimental trial published in an English peer-reviewed journal; (b) compared the effects of inorganic nitrate consumption with a non-bioactive supplement control or placebo; (c) used a quantifiable measure of exercise performance; and (d) was carried out in apparently healthy participants without disease. A total of 29 studies were identified that investigated the effects of nitrate supplementation on exercise tolerance or performance in accordance with the criteria outlined. Analysis using time to exhaustion as the outcome variable revealed a significant effect of nitrate supplementation on exercise tolerance (ES = 0.28; 95% confidence interval [CI]: 0.08-0.47; p = 0.006) compared with placebo. Analysis using time to complete a specific distance as the outcome variable revealed no significant effect of nitrate supplementation on exercise performance (ES = -0.05; 95% CI: -0.28 to 0.17; p = 0.64) compared with placebo. Nitrate supplementation is likely to improve exercise tolerance and capacity that may improve exercise performance. More research is required to determine the optimal dose and duration of nitrate supplementation. It would also be important to consider the type of athlete performing the exercise and the duration, intensity, and mode of the exercise performed because these factors are likely to influence the efficacy of nitrate supplementation.
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The effect of progressive resistance training on aerobic fitness and strength in adults with coronary heart disease: A systematic review and meta-analysis of randomised controlled trials.
Hollings, M, Mavros, Y, Freeston, J, Fiatarone Singh, M
European journal of preventive cardiology. 2017;(12):1242-1259
Abstract
Design We aimed to evaluate the effect of progressive resistance training on cardiorespiratory fitness and muscular strength in coronary heart disease, when compared to control or aerobic training, and when combined with aerobic training. Secondary aims were to evaluate the safety and efficacy of progressive resistance training on other physiological and clinical outcomes. Methods and results Electronic databases were searched from inception until July 2016. Designs included progressive resistance training vs control, progressive resistance training vs aerobic training, and combined training vs aerobic training. From 268,778 titles, 34 studies were included (1940 participants; 71.9% male; age 60 ± 7 years). Progressive resistance training was more effective than control for lower (standardized mean difference 0.57, 95% confidence interval (0.17-0.96)) and upper (1.43 (0.73-2.13)) body strength. Aerobic fitness improved similarly after progressive resistance training (16.9%) or aerobic training (21.0%); (standardized mean difference -0.13, 95% confidence interval (-0.35-0.08)). Combined training was more effective than aerobic training for aerobic fitness (0.21 (0.09-0.34), lower (0.62 (0.32-0.92)) and upper (0.51 (0.27-0.74)) body strength. Twenty studies reported adverse event information, with five reporting 64 cardiovascular complications, 63 during aerobic training. Conclusion Isolated progressive resistance training resulted in an increase in lower and upper body strength, and improved aerobic fitness to a similar degree as aerobic training in coronary heart disease cohorts. Importantly, when progressive resistance training was added to aerobic training, effects on both fitness and strength were enhanced compared to aerobic training alone. Reporting of adverse events was poor, and clinical gaps were identified for women, older adults, high intensity progressive resistance training and long-term outcomes, warranting future trials to confirm safety and effectiveness.
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Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance.
Figueroa, A, Wong, A, Jaime, SJ, Gonzales, JU
Current opinion in clinical nutrition and metabolic care. 2017;(1):92-98
Abstract
PURPOSE OF REVIEW L-Citrulline, either synthetic or in watermelon, may improve vascular function through increased L-arginine bioavailability and nitric oxide synthesis. This article analyses potential vascular benefits of L-citrulline and watermelon supplementation at rest and during exercise. RECENT FINDINGS There is clear evidence that acute L-citrulline ingestion increases plasma L-arginine, the substrate for endothelial nitric oxide synthesis. However, the subsequent acute improvement in nitric oxide production and mediated vasodilation is inconsistent, which likely explains the inability of acute L-citrulline or watermelon to improve exercise tolerance. Recent studies have shown that chronic L-citrulline supplementation increases nitric oxide synthesis, decreases blood pressure, and may increase peripheral blood flow. These changes are paralleled by improvements in skeletal muscle oxygenation and performance during endurance exercise. The antihypertensive effect of L-citrulline/watermelon supplementation is evident in adults with prehypertension or hypertension, but not in normotensives. However, L-citrulline supplementation may attenuate the blood pressure response to exercise in normotensive men. SUMMARY The beneficial vascular effects of L-citrulline/watermelon supplementation may stem from improvements in the L-arginine/nitric oxide pathway. Reductions in resting blood pressure with L-citrulline/watermelon supplementation may have major implications for individuals with prehypertension and hypertension. L-Citrulline supplementation, but not acute ingestion, have shown to improve exercise performance in young healthy adults.
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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.