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1.
Intravenous iron and chronic obstructive pulmonary disease: a randomised controlled trial.
Santer, P, McGahey, A, Frise, MC, Petousi, N, Talbot, NP, Baskerville, R, Bafadhel, M, Nickol, AH, Robbins, PA
BMJ open respiratory research. 2020;(1)
Abstract
BACKGROUND Increased iron availability modifies cardiorespiratory function in healthy volunteers and improves exercise capacity and quality of life in patients with heart failure or pulmonary hypertension. We hypothesised that intravenous iron would produce improvements in oxygenation, exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD). METHODS We performed a randomised, placebo-controlled, double-blind trial in 48 participants with COPD (mean±SD: age 69±8 years, haemoglobin 144.8±13.2 g/L, ferritin 97.1±70.0 µg/L, transferrin saturation 31.3%±15.2%; GOLD grades II-IV), each of whom received a single dose of intravenous ferric carboxymaltose (FCM; 15 mg/kg bodyweight) or saline placebo. The primary endpoint was peripheral oxygen saturation (SpO2) at rest after 1 week. The secondary endpoints included daily SpO2, overnight SpO2, exercise SpO2, 6 min walk distance, symptom and quality of life scores, serum iron indices, spirometry, echocardiographic measures, and exacerbation frequency. RESULTS SpO2 was unchanged 1 week after FCM administration (difference between groups 0.8%, 95% CI -0.2% to 1.7%). However, in secondary analyses, exercise capacity increased significantly after FCM administration, compared with placebo, with a mean difference in 6 min walk distance of 12.6 m (95% CI 1.6 to 23.5 m). Improvements of ≥40 m were observed in 29.2% of iron-treated and 0% of placebo-treated participants after 1 week (p=0.009). Modified MRC Dyspnoea Scale score was also significantly lower after FCM, and fewer participants reported scores ≥2 in the FCM group, compared with placebo (33.3% vs 66.7%, p=0.02). No significant differences were observed in other secondary endpoints. Adverse event rates were similar between groups, except for hypophosphataemia, which occurred more frequently after FCM (91.7% vs 8.3%, p<0.001). CONCLUSIONS FCM did not improve oxygenation over 8 weeks in patients with COPD. However, this treatment was well tolerated and produced improvements in exercise capacity and functional limitation caused by breathlessness. These effects on secondary endpoints require confirmation in future studies. TRIAL REGISTRATION NUMBER ISRCTN09143837.
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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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Repeated Wingate sprints is a feasible high-quality training strategy in moderate hypoxia.
Breenfeldt Andersen, A, Bejder, J, Bonne, T, Olsen, NV, Nordsborg, N
PloS one. 2020;(11):e0242439
Abstract
Sprint-interval training (SIT) is efficient at improving maximal aerobic capacity and anaerobic fitness at sea-level and may be a feasible training strategy at altitude. Here, it was evaluated if SIT intensity can be maintained in mild to moderate hypoxia. It was hypothesized that 6 x 30 s Wingate sprint performance with 2 min active rest between sprints can be performed in hypoxic conditions corresponding to ~3,000 m of altitude without reducing mean power output (MPO). In a single-blinded, randomized crossover design, ten highly-trained male endurance athletes with a maximal oxygen uptake ([Formula: see text]O2max) of 68 ± 5 mL O2 × min-1 × kg-1 completed 6 x 30 s all-out Wingate cycling sprints separated by two-minute active recovery on four separate days in a hypobaric chamber. The ambient pressure within the chamber on each experimental day was 772 mmHg (~0 m), 679 mmHg (~915 m), 585 mmHg (~ 2,150 m), and 522 mmHg (~3,050 m), respectively. MPO was not different at sea-level and up to ~2,150 m (~1% and ~3% non-significant decrements at ~915 and ~2,150 m, respectively), whereas MPO was ~5% lower (P<0.05) at ~3,050 m. Temporal differences between altitudes was not different for peak power output (PPO), despite a main effect of altitude. In conclusion, repeated Wingate exercise can be completed by highly-trained athletes at altitudes up to ~2,150 m without compromising MPO or PPO. In contrast, MPO was compromised in hypobaric hypoxia corresponding to ~3,050 m. Thus, SIT may be an efficient strategy for athletes sojourning to moderate altitude and aiming to maintain training quality.
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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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Efficacy and Safety of Inorganic Nitrate Versus Placebo Treatment in Heart Failure with Preserved Ejection Fraction.
Gui, Y, Chen, J, Hu, J, Ouyang, M, Deng, L, Liu, L, Sun, K, Tang, Y, Xiang, Q, Xu, J, et al
Cardiovascular drugs and therapy. 2020;(4):503-513
Abstract
BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is common, yet there is a lack of effective treatments. In this meta-analysis, we assessed the efficacy and safety of inorganic nitrate in patients with HFpEF. METHODS AND RESULTS We systematically searched PubMed, Embase, and the Cochrane Library from the inception of the database through March 2020. We included randomized controlled trials that compared the efficacy and safety of inorganic nitrate with a placebo in the treatment of patients with HFpEF. The primary outcome of the meta-analysis was exercise capacity (measured as a change in peak oxygen uptake). We also assessed the effect of inorganic nitrate on diastolic function (measured as changes in E/A and E/e', assessed by echocardiography), quality of life (estimated using the Kansas City Cardiomyopathy Questionnaire), and rest and exercise hemodynamics (measured by invasive cardiac catheterization). In the pooled data analysis, there were no significant differences in peak oxygen uptake (mL/kg/min) [mean difference (MD), 0.25; 95% CI, - 0.07 to 0.57], diastolic function [E/A-standardized mean difference (SMD), 0.51; 95% CI, - 0.17 to 1.20; or E/e'-SMD, 0.02; 95% CI, - 0.23 to 0.27], or quality of life. However, a significant change was observed in the rest and exercise hemodynamics between the inorganic nitrate and placebo treatment in HFpEF patients. No study has reported the effect of inorganic nitrate on hospitalization and mortality of patients with HFpEF. CONCLUSIONS In patients with HFpEF, the use of inorganic nitrate is not associated with improvements in exercise capacity, diastolic function, and quality of life but is associated with significant changes in rest and exercise hemodynamics.
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Influence of muscle oxygenation and nitrate-rich beetroot juice supplementation on O2 uptake kinetics and exercise tolerance.
Cocksedge, SP, Breese, BC, Morgan, PT, Nogueira, L, Thompson, C, Wylie, LJ, Jones, AM, Bailey, SJ
Nitric oxide : biology and chemistry. 2020;:25-33
Abstract
We tested the hypothesis that acute supplementation with nitrate (NO3-)-rich beetroot juice (BR) would improve quadriceps muscle oxygenation, pulmonary oxygen uptake (V˙O2) kinetics and exercise tolerance (Tlim) in normoxia and that these improvements would be augmented in hypoxia and attenuated in hyperoxia. In a randomised, double-blind, cross-over study, ten healthy males completed two-step cycle tests to Tlim following acute consumption of 210 mL BR (18.6 mmol NO3-) or NO3--depleted beetroot juice placebo (PL; 0.12 mmol NO3-). These tests were completed in normobaric normoxia [fraction of inspired oxygen (FIO2): 21%], hypoxia (FIO2: 15%) and hyperoxia (FIO2: 40%). Pulmonary V˙O2 and quadriceps tissue oxygenation index (TOI), derived from multi-channel near-infrared spectroscopy, were measured during all trials. Plasma [nitrite] was higher in all BR compared to all PL trials (P < 0.05). Quadriceps TOI was higher in normoxia compared to hypoxia (P < 0.05) and higher in hyperoxia compared to hypoxia and normoxia (P < 0.05). Tlim was improved after BR compared to PL ingestion in the hypoxic trials (250 ± 44 vs. 231 ± 41 s; P = 0.006; d = 1.13), with the magnitude of improvement being negatively correlated with quadriceps TOI at Tlim (r = -0.78; P < 0.05). Tlim was not improved following BR ingestion in normoxia (BR: 364 ± 98 vs. PL: 344 ± 78 s; P = 0.087, d = 0.61) or hyperoxia (BR: 492 ± 212 vs. PL: 472 ± 196 s; P = 0.273, d = 0.37). BR ingestion increased peak V˙O2 in hypoxia (P < 0.05), but not normoxia or hyperoxia (P > 0.05). These findings indicate that BR supplementation is more likely to improve Tlim and peak V˙O2 in situations when skeletal muscle is more hypoxic.
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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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Effects of Intermittent Fasting on Specific Exercise Performance Outcomes: A Systematic Review Including Meta-Analysis.
Correia, JM, Santos, I, Pezarat-Correia, P, Minderico, C, Mendonca, GV
Nutrients. 2020;(5)
Abstract
Intermittent fasting (IF) has been studied in athletes during Ramadan and in those willing to decrease adiposity while maintaining or increasing lean body mass. The purpose of this systematic review was to summarize the effects of IF on performance outcomes. We searched peer-reviewed articles in the following databases: PubMed, Web of Science and Sport Discus (up to December 2019). Studies were selected if they included samples of adults (≥18 years), had an experimental or observational design, investigated IF (Ramadan and time-restricted feeding (TRF)), and included performance outcomes. Meta-analytical procedures were conducted when feasible. Twenty-eight articles met the eligibility criteria. Findings indicated that maximum oxygen uptake is significantly enhanced with TRF protocols (SMD = 1.32, p = 0.001), but reduced with Ramadan intermittent fasting (Ramadan IF; SMD = -2.20, p < 0.001). Additional effects of IF may be observed in body composition (body mass and fat mass). Non-significant effects were observed for muscle strength and anaerobic capacity. While Ramadan IF may lead to impairments in aerobic capacity, TRF may be effective for improving it. As there are few studies per performance outcome, more research is needed to move the field forward.
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Cardiac rehabilitation of elderly patients in eight rehabilitation units in western Europe: Outcome data from the EU-CaRE multi-centre observational study.
Prescott, E, Eser, P, Mikkelsen, N, Holdgaard, A, Marcin, T, Wilhelm, M, Gil, CP, González-Juanatey, JR, Moatemri, F, Iliou, MC, et al
European journal of preventive cardiology. 2020;(16):1716-1729
Abstract
AIMS: The European Cardiac Rehabilitation in the Elderly (EU-CaRE) HORIZON 2020 project compares the sustainable effects of cardiac rehabilitation (CR) in elderly patients. METHODS AND RESULTS A total of 1633 patients with coronary artery disease (CAD) or heart valve replacement (HVR), with or without revascularization, aged 65 or above, who participated in CR were included. Peak oxygen uptake (VO2peak), smoking, body mass index, diet, physical activity, serum lipids, psychological distress and medication were assessed before and after CR (T0 and T1) and after 12 months (T2). Patients undergoing coronary artery bypass surgery or surgical HVR had lower VO2peak at T0 and a greater increase to T1 and T2 (2.8 and 4.4 ml/kg/min, respectively) than CAD patients undergoing percutaneous or no revascularization (1.6 and 1.4 ml/kg/min, respectively). After multivariable adjustment, earlier CR uptake was associated with greater improvements in VO2peak. The proportion of CAD patients with three or more uncontrolled risk factors declined from 58.4% at T0 to 40.1% at T2 (p < 0.0001). Psychological distress scores all improved and adherence to medication was overall good at all sites. There were significant differences in risk factor burden across sites, but no CR program was superior to others. CONCLUSIONS The outcomes of VO2peak in CR programs across Europe seemed mainly determined by timing of uptake and were maintained or even further improved at 1-year follow-up. Despite significant improvements, 40.1% of CAD patients still had three or more risk factors not at target after 1 year. Differences across sites could not be ascribed to characteristics of the CR programs offered.