Similar maximal aerobic capacity but lower energy efficiency during low-to-moderate exercise in women with constitutional thinness: new results from the NUTRILEAN study.

PURPOSE: Individuals with constitutional thinness have been presented with a lower muscular energy metabolism at the cellular level but their effective aerobic capacities and exercise-related energy efficiency remains unexplored. The present study compares maximal and sub-maximal aerobic capacities between subjects with constitutional thinness and age-matched normal-weight ones. METHODS: Anthropometric measures, body composition (Dual-X-ray absorptiometry), physical activity and sedentary time (GT3x actigraphs), and maximal aerobic capacities (cycling V ˙ O 2peak test) were assessed in 18 constitutionally thin (CT-body mass index < 17.5 kg m-2) and 17 normal-weight (NW-body mass index between 20 and 25 kg m-2) women. Energy efficiency was assessed during a submaximal cycling test and a walking exercise. RESULTS: CT had a lower body mass and body mass index compared to NW. Absolute peak oxygen uptake and maximal aerobic power were lower in CT subjects compared to NW (ES: - 1.63 [- 2.40; - 0.86] and - 1.32 [- 2.05; - 0.58], p < 0.001). V ˙ O 2peak related to body mass was not different between groups. Gross and net efficiency (ES: - 0.78 [- 1.48; - 0.06], p = 0.03 and ES: - 0.73 [- 1.43; - 0.01], p = 0.05) were lower in CT compared to NW during the submaximal cycling exercise. The gross energy cost of walking related to body mass was lower in subjects with CT (ES: - 1.80 [- 2.60; - 0.97, p = 0.05), with no difference for the net one. Perceived exertion was similar between groups in responses to both submaximal exercises. CONCLUSION: Constitutionally thin women do not show impaired aerobic capacities at moderate to maximal intensities despite lower energy efficiency while cycling and walking at low-to-moderate intensities.

Post-exercise energy replacement might lead to reduced subsequent energy intake in women with constitutional thinness: Exploratory results from the NUTRILEAN project.

While people with Constitutional Thinness (CT) declare a deep willingness to gain weight, there appetitive responses to energy balance manipulations remain unclear. The present work compares the effect of an acute exercise combined or not with an energy replacement load, on subsequent energy intake, appetite and food reward, between normal weight and women with CT. Anthropometric measurements, body composition (Dual X-ray absorptiometry-DXA) and aerobic capacity (VO2max) were assessed in 10 normal-weight (Body Mass Index-BMI): 20-25 kg/m2) and 10 C T (BMI<17.5 kg/m2) women (18-30 years). They randomly performed i) a resting session (CON); ii) an exercise session (EX); iii) an exercise session with energy replacement (EX + R). Their subsequent ad libitum intake, appetite feelings and food reward were evaluated (Leeds-Food-Preference-Questionnaire). CT showed a lower weight (p < 0,001), BMI(p < 0,001), Fat-Mass (%) (p = 0,003) and Fat-Free Mass (kg) (p < 0,001). CT showed a lower ad libitum energy intake on EX + R compared with CON (p = 0,008) and a higher Relative Energy Intake (REI) on CON compared with EX (p = 0,007) and EX + R (p < 0,001). A lower was observed during EX and EX + R compared with CON (p = 0,006,p = 0,009 respectively) in CT. No condition nor group effect was found for hunger. NW only showed a higher pre-meal fullness on EX + R compared to CON and EX (p < 0,001). Choice (p = 0,030), Explicit Liking (p = 0,016), Explicit Wanting (p = 0,004) and Implicit Wanting (p = 0,035) for taste were higher on EX + R than CON and EX. The decreased EI observed in CT when the exercise-induced energy expenditure is compensated by the ingestion of an equivalent energy load, might contribute to explain the difficulty to increase their energy balance and then induce weight gain. Further studies are needed to better understand their energy balance regulation to propose adapted weight gain strategies.

Challenges of considering both extremities of the weight status spectrum to better understand obesity: insights from the NUTRILEAN project in constitutionally thin individuals.

BACKGROUND/OBJECTIVES: While the physiology of obesity has been so extensively investigated to date, only an extremely small number of studies (less than 50) have focused on the other extremity of the weight spectrum: constitutional thinness. Yet, this important state of underweight in the absence of any eating disorders provides a mirror model of obesity that might be particularly insightful in understanding obesity. Nevertheless, important methodological and recruitment-related issues appear when it comes to this complex constitutionally thin phenotype, as experienced by our research group with the realization of the ongoing NUTRILEAN clinical trial. To face this challenge, the present paper aims at identifying, analyzing, and discussing the quality of such recruitment processes in publications about constitutional thinness. METHODS: In this order, a group of experts collectively created a new grading system to assess the level of rigour and quality achieved by each study based on different criteria. RESULTS: The main results were that (i) metabolic-related biasing criteria were poorly observed despite being crucial, (ii) recruitment processes were not detailed enough and with sufficient explicitness, and (iii) recruiting among already identified patients would be associated with both higher sample sizes and better scores of quality. CONCLUSIONS: The present work encourages investigators to adopt a high level of rigour despite the complexity and duration of recruitment processes for this specific population, and readers to pay close attention to the quality of recruitment when interpreting the data. To better understand obesity and its physiological adaptations, it seems essential not only to compare it to normal-weight conditions, but also to the other extremity of the weight status spectrum represented by constitutional thinness.

The effect of a pressure ventilatory support on quadriceps endurance is maintained after exercise training in severe COPD patients. A longitudinal randomized, cross over study.

Purpose: In severe chronic obstructive pulmonary disease (COPD) patients, the application of an inspiratory pressure support (IPS) during exercise increases exercise tolerance and the benefit of exercise training during pulmonary rehabilitation (PR). Moreover, it improves quadriceps endurance after a session of cycling exercise suggesting a reduced muscle fatigue. We looked for the persistence of this effect after PR and sought an association between the improved quadriceps endurance with IPS and the training load during PR. Patients and methods: We studied 20 patients with severe COPD (6 in stage 3and 14 in stage 4 of GOLD) before and after PR. As part of a PR program, patients completed 16 cycling sessions over 6 weeks with the addition of IPS during exercise. As a surrogate of muscular fatigue, quadriceps endurance was measured at 70% of maximal strength in a control condition, after a constant work rate exercise test (CWR) with IPS (TlimQ IPS) or with a sham ventilation (TlimQsham), in a random order. These tests were repeated similarly at the end of PR. Results: PR was associated with a significant increase in maximal power output, cycling endurance, quadriceps strength and endurance. Session training load (power output x duration of the session) increased by 142% during the course of the program. Before PR, CWR duration increases with IPS compared to sham ventilation (Δtime = +244s, p = 0.001). Compared to control condition, post-exercise TlimQ reduction was lower with IPS at isotime than at the end of CWR or than with sham ventilation (-9 ± 21%, -18 ± 16% and -23 ± 18%, respectively, p = 0.09, p < 0.0001 and p < 0.0001). After PR, the post-exercise decrease of TlimQ was reduced after IPS compared to sham (-9 ± 18% vs. -21 ± 17%, respectively, p = 0.004). No relationship was found between the prevention of quadriceps fatigue and the training load. Conclusion: In severe COPD patients, the beneficial effect of a ventilator support on quadriceps endurance persisted after PR with IPS. However, it was not related to the increase in training load, and could not predict the training response to non-invasive ventilation during exercise.

New Insights on Bone Tissue and Structural Muscle-Bone Unit in Constitutional Thinness.

While few studies pointed out low bone mineral densities in constitutionally thin women, little is known about potential explanations. The objective was to further explore bone architecture in both women and men with constitutional thinness to investigate their mechanical muscle-bone coupling (or uncoupling). Thirty constitutionally thin people and 31 normal weight controls participated in the study. Body composition, hip structural analysis, and trabecular bone score were assessed by dual-energy X-ray absorptiometry, bone architecture using high-resolution peripheral quantitative computed tomography, and muscle explorations through histological staining on muscle biopsies. Thirty-two out of the 48 indexes relative to density, geometry, texture, and architecture of bones were found significantly lower (p < 0.05) in constitutionally thin individuals compared with controls. This observation was particularly pronounced in constitutionally thin men. Bone microarchitecture was more altered in weight-supporting bone (tibia) than in non-weight-supporting (radius) bone, which might refer to a normal physiological adaptation (Frost's mechanostat theory). Yet, the heat-maps of correlations analyses showed many alterations of body weight or muscle associations with bone parameters in constitutionally thin individuals contrary to controls. Present results might support the idea of intrinsic disturbances of bone cells independently to the small muscle structure, particularly in men.

Effects of exercise-induced metabolic and mechanical loading on skeletal muscle mitochondrial function in male rats.

Over the past decades, a growing interest in eccentric (ECC) exercise has emerged, but mitochondrial adaptations to ECC training remain poorly documented. Using an approach for manipulating mechanical and metabolic exercise power, we positioned that for the same metabolic power, training using concentric (CON) or ECC contractions would induce similar skeletal muscle mitochondrial adaptations. Sixty adult rats were randomly assigned to a control (CTRL) or three treadmill training groups running at 15 m·min-1 for 45 min, 5 days weekly for 8 wk at targeted upward or downward slopes. Animals from the CON (+15%) and ECC30 (-30%) groups were trained at iso-metabolic power, whereas CON and ECC15 (-15%) exercised at iso-mechanical power. Assessments were made of vastus intermedius mitochondrial respiration (oxygraphy), enzymatic activities (spectrophotometry), and real-time qPCR for mRNA transcripts. Maximal rates of mitochondrial respiration were 14%-15% higher in CON and ECC30 compared with CTRL and ECC15. Apparent Km for ADP for trained groups was 40%-66% higher than CTRL, with statistical significance reached for CON and ECC30. Complex I and citrate synthase activities were 1.6 (ECC15) to 1.8 (ECC30 and CON) times values of CTRL. Complex IV activity was higher than CTRL (P < 0.05) only for CON and ECC30. mRNA transcripts analyses showed higher TFAM, SLC25A4, CKMT2, and PPID in the ECC30 compared with CTRL. Findings confirm that training-induced skeletal muscle mitochondrial function adaptations are governed by the extent of metabolic overload irrespective of exercise modality. The distinctive ECC30 mRNA transcript pattern may reflect a cytoskeleton damage-repair or ECC adaptive cycle that differs from that of biogenesis.NEW & NOTEWORTHY Anticipating outcomes of eccentric versus concentric training is confounded by differences in mechanical efficiency. Our observations in groups of rats submitted to uphill and downhill running regimens inducing similar levels of metabolic demands or same external power outputs reaffirm that independent of modality, oxygen requirements and not external work governs skeletal muscle mitochondrial function adaptations.

Fine Detection of Human Motion During Activities of Daily Living as a Clinical Indicator for the Detection and Early Treatment of Chronic Diseases: The E-Mob Project.

Methods to measure physical activity and sedentary behaviors typically quantify the amount of time devoted to these activities. Among patients with chronic diseases, these methods can provide interesting behavioral information, but generally do not capture detailed body motion and fine movement behaviors. Fine detection of motion may provide additional information about functional decline that is of clinical interest in chronic diseases. This perspective paper highlights the need for more developed and sophisticated tools to better identify and track the decomposition, structuration, and sequencing of the daily movements of humans. The primary goal is to provide a reliable and useful clinical diagnostic and predictive indicator of the stage and evolution of chronic diseases, in order to prevent related comorbidities and complications among patients.

Eccentric Cycling Training Improves Health-Related Quality of Life in Adolescents with Obesity.

INTRODUCTION: While eccentric (ECC) training appears to be more efficient than concentric (CON) training at improving body composition in adolescent with obesity, its impact on health-related quality of life (HRQOL) has never been studied. OBJECTIVE: The aim of this study is to compare the effects of 2 cycling training modalities, i.e., ECC vs. CON, in adolescents with obesity on HRQOL and health perception (HP). METHODS: A total of 24 adolescents with obesity, aged 12-16 years, were randomized to either a 12-week ECC or a CON cycling training program performed at the same oxygen consumption (VO2). Anthropometric measurements, body composition, maximal incremental tests, HRQOL (Vécu et Santé Percue de l'Adolescent [VSP-A], Medical Outcome Study Short Form [SF-36]), and HP were assessed at before and after training. RESULTS AND CONCLUSION: Both CON and ECC cycling trainings promoted significant improvements in BMI, VO2peak, total fat mass, and fat-free mass, with better improvements in body composition parameters in the ECC group (p < 0.05). The VSP-A total score increased after CON (p < 0.01) and ECC (p < 0.001) training, with better enhancement for the ECC group (p < 0.05). The SF-36 physical score increased after both CON (p < 0.01) and ECC (p < 0.001) trainings. The global HP score increased only after ECC training (p < 0.001). Except for the energy-vitality item, no significant correlation was found between changes in HRQOL and its subdomains and anthropometric, body composition, and functional parameters. Both ECC and CON cycling trainings are associated with positive changes in HRQOL and HP. However, ECC seems to induce greater improvements in HRQL and HP than CON cycling training, which is probably not due to the anthropometric, body composition, and functional changes.

Core Outcome Measurement Instruments for Clinical Trials of Total Knee Arthroplasty: A Systematic Review.

(1) Background: We have updated knowledge of the psychometric qualities of patient-reported outcome measures and, for the first time, systematically reviewed and compared the psychometric qualities of physical tests for patients with knee osteoarthritis who are undergoing total knee arthroplasty. This work was conducted to facilitate the choice of the most appropriate instruments to use in studies and clinical practice. (2) Methods: A search of medical databases up to December 2019 identified the studies and thus the instruments used. The quality of the measurement properties was assessed by the Bot et al. criteria. (3) Results: We identified 20 studies involving 25 instruments. Half of the instruments were questionnaires (n = 13). Among the condition-specific instruments, the Oxford knee score, Knee injury and Osteoarthritis Outcomes Score, and the Western Ontario and McMaster Universities Osteoarthritis index had the highest overall scores. Concerning generic tools, the Medical Outcomes Study Short-Form 36 (SF-36) or SF-12 obtained the highest overall score. For patient-specific tools, the Hospital Anxiety and Depression Scale ranked the highest. Some physical tests seemed robust in psychometric properties: 6-min Walk Test, five times Sit-To-Stand test, Timed Up and Go test strength testing of knee flexor/extensor by isometric or isokinetic dynamometer and Pressure Pain Threshold. (4) Conclusion: To make stronger recommendations, key areas such as reproducibility, responsiveness to clinical change, and minimal important change still need more rigorous evaluations. Some promising physical tests (e.g., actimetry) lack validation and require rigorous studies to be used as a core set of outcomes in future studies.

Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile.

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (-17%, p < 0.01) and type IIA (-14%, p < 0.05) muscle fibers, a lower glycogen content for type I (-6%, p < 0.01) and type IIA (-5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (-20%, p < 0.001), a low capillary-to-fiber ratio (-19%, p < 0.001), and low citrate synthase activity (-18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

Aerobic Metabolic Adaptations in Endurance Eccentric Exercise and Training: From Whole Body to Mitochondria.

A characteristic feature of eccentric as compared with concentric exercise is the ability to generate greater mechanical loads for lower cardiopulmonary demands. Current evidence concurs to show that eccentric training translates into considerable gains in muscle mass and strength. Less is known, however, regarding its impact on oxygen transport and on factors to be considered for optimizing its prescription and monitoring. This article reviews the existing evidence for endurance eccentric exercise effects on the components of the oxygen transport system from systemic to mitochondria in both humans and animals. In the studies reviewed, specially designed cycle-ergometers or downhill treadmill running were used to generate eccentric contractions. Observations to date indicate that overall, the aerobic demand associated with the eccentric training load was too low to significantly increase peak maximal oxygen consumption. By extension, it can be inferred that the very high eccentric power output that would have been required to solicit a metabolic demand sufficient to enhance peak aerobic power could not be tolerated or sustained by participants. The impact of endurance eccentric training on peripheral flow distribution remains largely undocumented. Given the high damage susceptibility of eccentric exercise, the extent to which skeletal muscle oxygen utilization adaptations would be seen depends on the balance of adverse and positive signals on mitochondrial integrity. The article examines the protection provided by repeated bouts of acute eccentric exercise and reports on the impact of eccentric cycling and downhill running training programs on markers of mitochondrial function and of mitochondrial biogenesis using mostly from animal studies. The summary of findings does not reveal an impact of training on skeletal muscle mitochondrial respiration nor on selected mitochondrial messenger RNA transcripts. The implications of observations to date are discussed within future perspectives for advancing research on endurance eccentric exercise physiological impacts and using a combined eccentric and concentric exercise approach to optimize functional capacity.

Autonomic cardiovascular adaptations to acute head-out water immersion, head-down tilt and supine position.

PURPOSE: Thermoneutral head-out water immersion (WI) and 6° head-down tilt (HDT) have been considered as suitable models to increase central blood volume and simulate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving. However, any differences in autonomic cardiovascular adaptations are still unclear. In this study, we hypothesized that WI induces a higher activation of arterial baroreceptors and the parasympathetic system. METHODS: Ten healthy men underwent 30 min of WI, HDT, and a supine position (SP). RR intervals (RRI) and blood pressure (BP) were continuously monitored. High frequency power (HF), low frequency power (LF) and LF/HF ratio were calculated to study sympathetic and parasympathetic activities, and a spontaneous baroreflex method was used to study arterial baroreflex sensitivity (aBRS). Lung transfer of nitric oxide and carbon monoxide (TLNO/TLCO), vital capacity and alveolar volume (Vc/VA) were measured to study central blood redistribution. RESULTS: We observed (1) a similar increase in RRI and decrease in BP; (2) a similar increase in HF power during all experimental conditions, whereas LF increased after; (3) a similar rise in aBRS; (4) a similar increase in Vc/VA and decrease in TLNO/TLCO in all experimental conditions. CONCLUSIONS: These results showed a cardiac parasympathetic dominance to the same extent, underpinned by a similar arterial baroreflex activation during WI and HDT as well as control SP. Future studies may address their association with cold or hyperoxia to assess their ability to replicate autonomic cardiovascular adaptations to microgravity, swimming or scuba diving.

Preoperative respiratory muscle endurance training improves ventilatory capacity and prevents pulmonary postoperative complications after lung surgery.

BACKGROUND: Resection surgery is the main treatment for non-small cell lung cancer (NSCLC). Postoperative complications and mortality are mostly linked to respiratory failure consecutive to respiratory muscle overload. AIM: We aimed to evaluate the effect of preoperative respiratory muscle endurance training (RMET) on respiratory muscle capacity and postoperative complications in patients undergoing NSCLC resection. DESIGN: Randomized controlled trial. SETTING: French university hospital. POPULATION: Patients eligible for NSCLC resection. METHODS: The training group (T group) performed a 3-week preoperative RMET added to usual chest physical therapy while the control group (C group) had only the latter. The primary outcome was the change in respiratory muscle endurance. Secondary outcomes were postoperative complications and mortality. Assessments were performed similarly at baseline and after the intervention. We conducted multivariable analyses with analysis of covariance (ANCOVA) taking into account baseline values for isocapnic hyperpnoea endurance test, exercise capacity and pulmonary function tests. The number of pulmonary postoperative complication was analyzed by Fisher-exact test. RESULTS: We included 26 patients with NSCLC (14 in the T group and 12 in the C group). Respiratory muscle endurance significantly increased in the T group after the RMET compared with C group (+229±199 vs. -5±371 sec, P=0.001). This increase was associated with a significantly lower number of pulmonary postoperative complications (2 vs. 10, P=0.037). CONCLUSIONS: Preoperative RMET improved respiratory muscle endurance and decreased pulmonary postoperative complications after surgery for NSCLC. These positive results obtained after RMET may help improve the perioperative course for such patients. These results should be confirmed in larger randomized controlled trials, including higher number of patients especially with altered respiratory muscle function. CLINICAL REHABILITATION IMPACT: Low-cost and easy to perform, RMET training could serve as complementary tool to usual chest physical therapy, before lung resection surgery.

Quadriceps Endurance Increases Following Cycling Exercise With Non-Invasive Ventilation In Moderate-To-Severe COPD Patients. A Non-Randomized Controlled Study.

Purpose: Application of non-invasive ventilation (NIV) during exercise improves exercise tolerance in severe COPD patients; however, the underlying mechanism is only partially unraveled. As part of its known effect to unload the respiratory muscles, we looked for the influence of NIV on post-exercise quadriceps muscle endurance. Patients and methods: We included 25 severe COPD patients entering an outpatient pulmonary rehabilitation program. They performed, on successive days, three quadriceps endurance tests at 70% of the maximal strength (1RM) to task failure (TlimQ); 1) control condition; 2) following constant load cycling exercise to exhaustion without Inspiratory Pressure Support (TlimQ IPS-); 3) following the same cycling exercise with IPS (TlmQ IPS+). Results: Dyspnea Borg score was significantly reduced at the end of the constant load cycling exercise with IPS+ compared to IPS- (3.5±2.6 to 4.3±2.3, p<0.05). Compared to controlled condition, TlimQ was reduced from 78.9±22.7 s to 64.7±22.1 s (p<0.01) with IPS+ and to 48.9±13.7 s (p<0.001) with IPS-. Sensitive analysis revealed a positive effect of NIV on TlimQ in only 15 of the 25 included patients (60%) and was unpredictable from exercise tolerance or maximal quadriceps strength. Conclusion: Using a simple muscle endurance test, we showed the protective effect of NIV on the exercise-induced quadriceps dysfunction. This beneficial effect is inconstant in our small series of patients and could not be predicted by exercise capacity or endurance to exercise. However, measuring quadriceps muscle endurance following a session of exercise could determine in which patient NIV would improve the benefit of pulmonary rehabilitation.

A TUG Value Longer Than 11 s Predicts Fall Risk at 6-Month in Individuals with COPD.

Risk of a fall is increased in individuals with chronic obstructive pulmonary disease (COPD), and is usually evaluated using the Berg Balance Scale (BBS), but this is difficult to perform in everyday clinical practice. We aimed to prospectively predict short-term fall recurrence in COPD patients using a predetermined cut-off value of the Timed Up and Go test (TUG). In stable COPD patients, we collected self-reported records of the number of falls in the previous year, and measured TUG and BBS scores for each individual. Records of fall recurrence were obtained prospectively at 6-months after the initial evaluation. Among the 50 patients recruited, 23 (46%) had at least one fall during the past year. The optimal diagnosis value for the TUG to detect a fall was 10.9 s with a sensitivity of 100% and a specificity of 97%. A cut-off of 11 s predicted fall recurrence with high sensitivity and specificity (93% and 74%, respectively). The TUG as well as the BBS score detected fallers, and a cut-off value of 11 s predicted fall recurrence. TUG could be easily incorporated into the scheduled functional evaluations of COPD patients, could predict the risk of a fall and when appropriate, could guide specific balance training exercises to prevent fall.

Effectiveness of combined eccentric and concentric exercise over traditional cardiac exercise rehabilitation programme in patients with chronic heart failure: protocol for a randomised controlled study.

INTRODUCTION: Exercise-based rehabilitation is a standard feature of chronic heart failure management. The effectiveness of eccentric exercise could offer new opportunities for better tailoring rehabilitation programme to patients' limitations. The goal of the study is to contrast the impact of a mixed eccentric and concentric cycling training programme, to that of conventional concentric cycling rehabilitation in patients with chronic heart failure (peak oxygen consumption (VO2Peak) < 15 mL⋅kg-1⋅min-1, ejection fraction <40%). METHODS AND ANALYSIS: It is a prospective, open, controlled and randomised study (2×25 subjects) carried out in a single centre. Subjects will perform five exercise sessions per week per the randomisation outcome, with the intervention group performing eccentric in three of the five weekly sessions while the control group will perform the five sessions of concentric exercise. Cycling intensity will be the same in both groups and fixed to the power associated with the first ventilatory threshold. Self-management education programme, callisthenics sessions and muscle strength trainings will also be carried out as for any heart failure patient normally included in the rehabilitation programme. The primary outcome will be the change in distance covered during the 6 min walk test. Secondary outcomes will include other physical mobility parameters, functional exercise capacities, quality of life and body composition as well as skeletal muscle properties including mitochondrial function parameters. ETHICS AND DISSEMINATION: The study has been approved by the institutional ethics review board (17.079) and the French regulatory authority for research (2017-A00969-44). Adverse events that could occur during the protocol will be reported to the principal investigator. The results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03716778.

Effect of exercise training on heart rate variability in patients with obstructive sleep apnea: A randomized controlled trial.

While obstructive sleep apnea (OSA) increases chemoreflex, leading to an autonomic dysfunction in the long term, no studies have yet assessed the potential benefit of exercise on cardiac autonomic activity in these patients. The aim of this study was to evaluate potential improvement in cardiac autonomic function (CAF) measured through heart rate variability (HRV) after a 9-month physical activity program in patients with OSA. Seventy-four patients with moderate OSA, aged 40-80 years, were randomly assigned to an exercise group (n = 36, 3 × 1 h/wk) or a control group (n = 38) during 9 months. Linear and nonlinear HRV parameters were measured during night using a Holter ECG. After 9 months, mean R-R intervals increased in the exercise group without any changes in HRV parameters, while controls decreased global (standard deviation of normal-to-normal intervals, total power) and parasympathetic (root mean square successive difference of N-Ns, very low frequency, high frequency, and standard deviation of the instantaneous beat-to-beat variability) indices of HRV (P < 0.05 for all). Significant correlations with moderate effect size were found between changes in apnea severity and changes in R-R intervals (P < 0.05). Improvement in moderate-to-vigorous physical activity was also correlated to improvement in nocturnal oxygen parameters (P < 0.05). In conclusion, supervised community physical activity may prevent a decline in nighttime CAF observed in nontreated community-dwelling patients with moderate OSA over a 9-month period. Thus, beyond apnea-hypopnea index improvement, exercise may be cardioprotective in OSA patients through bradycardia, CAF preservation, and VO2peak increase.

Validation of intracardiac shunt using thoracic bioimpedance and inert gas rebreathing in adults before and after percutaneous closure of atrial septal defect in a cardiology research unit: study protocol.

INTRODUCTION: Intrathoracic shunt quantification is a major factor for appropriate clinical management of heart and pulmonary diseases. Intracardiac shunts quantified by pulmonary to systemic output ratio (Qp/Qs) are generally assessed by Doppler echocardiography, MRI or catheterisation. Recently, some authors have suggested the concomitant use of thoracic bioimpedance (TB) and inert gas rebreathing (IGR) techniques for shunt quantification. The purpose of this study is to validate the use of this approach under conditions where shunt fraction is directly quantified such as in patients with isolated atrial septal defect (ASD). METHODS AND ANALYSIS: This trial is a prospective, observational single-centre, non-blinded study of adults seen for percutaneous closure of ASD. Qp/Qs ratio will be directly measured by Doppler echocardiography and direct Fick. IGR and TB will be used simultaneously to measure the cardiac output before and after closure: the ratio of outputs measured by IGR and TB reflecting the shunt fraction. The primary outcome will be the comparison of shunt values measured by TB-IGR and Doppler echocardiography. ETHICS AND DISSEMINATION: The study has been approved by an independent Research Ethics Committee (2017-A03149-44 Fr) and registered as an official clinical trial. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03437148; Pre-results.

Does obstructive sleep apnea affect exercise capacity and the hemodynamic response to exercise? An individual patient data and aggregate meta-analysis.

Obstructive sleep apnea (OSA) has been linked to altered cardiovascular response to exercise. A systematic review and individual patient data (IPD) meta-analysis were conducted to assess whether OSA patients present reduced exercise capacity. PubMed, Embase and Web of Science were searched until September 2018. Studies which performed sleep recording in both OSA patients and controls and measured maximal oxygen consumption (VO2peak) via a maximal exercise test were included. IPD were provided for five trials upon the 18 eligible (N = 289) and a two-stage IPD meta-analysis model was used, allowing to standardize the apnea cutoff and adjust for confounders. IPD meta-analysis demonstrated that moderate to severe OSA patients had similar VO2peak (mean difference: -1.03 mL·kg-1 min-1; 95% CI: -3.82 to 1.76; p = 0.47) and cardiovascular response to exercise compared to mild or non-OSA patients. By contrast, aggregate data (AD) meta-analysis including the 13 trials for which IPD were unavailable (N = 605) revealed that VO2peak was reduced in OSA patients compared to controls (mean difference: -2.30 mL·kg-1 min-1; 95% CI: -3.96 to -0.63; p < 0.001) with high heterogeneity. In conclusion, IPD meta-analysis suggests that VO2peak and the cardiovascular response to exercise are preserved in moderate to severe OSA patients while AD meta-analysis suggests lower VO2peak in severe OSA.