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Background: Knowledge about how patients with symptomatic aortic stenosis (AS) perform on cardiopulmonary exercise testing (CPET) is sparse. Since exercise testing in patients with symptomatic AS is not advised, submaximal parameters could be of special interest. We aimed to investigate maximal and submaximal physical capacity by CPET before and 1 year after surgical aortic valve replacement (sAVR) in patients with severe AS., Methods: In this prospective longitudinal study, 30 adult patients (age 66±10 years) with severe AS referred for sAVR underwent maximal CPET (respiratory exchange ratio ≥1.05) on a bicycle ergometer before (PRE) and 1 year after (POST) sAVR. Normally distributed data are presented as mean (±SD) and non-normally distributed data are presented as median (IQR)., Results: Median peak workload increased by 8% from 133 (55) watts at PRE to 144 (67) watts at POST (p<0.001). Median ventilatory threshold (VO 2 @VT) increased from 1216 (391) to 1328 (309) mL/min (p=0.001, n=28). Mean peak oxygen uptake (peakVO 2 ) was not significantly different between PRE and POST; 1871±441 vs 1937±404 mL/min (p=0.08). The oxygen uptake efficacy slope (OUES) was significantly correlated to PeakVO2 at both PRE (r=0.889, p<0.05) and POST (r=0.888, p<0.05) CONCLUSION: Physical work capacity was improved 1 year following sAVR, in terms of higher median peak workload and VO 2 @VT. The strong correlation between the submaximal variable OUES and peakVO 2 suggests that OUES might be a useful surrogate of peakVO 2 in this group of patients where maximal exercise testing is not always recommended., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Diabetes mellitus (DM) and heart failure (HF) share vascular, skeletal and metabolic abnormalities that can reduce exercise capacity. We investigated whether exercise capacity differ in patients with type 2 DM compared to those without DM with HF of similar severity., Methods and Results: The Studies Investigating Co-morbidities Aggravating HF (SICA-HF) prospectively enrolled 615 patients with chronic HF, 259 (42.1 %) of whom had DM. We assembled a propensity score-matched cohort of 231 pairs of patients with HF with or without DM who were balanced on age, sex and variables reflecting HF severity. Patients with DM had lower median peak VO 2 (15.7 [13.0-19.1] vs. 17.3 [14.1-21.0] ml/min/kg; p = 0.005). Forearm blood flow reserve (per 1 ml/min/100 ml increase) was associated with lower exercise capacity (peak VO2 ≤ 16.6 ml/min/kg) in patients with DM (OR, 0.92; 95 % CI, (0.85-0.98; p = 0.014), but not in those without DM (OR, 0.98; 95 % CI, 0.93-1.02). A similar heterogeneity was also observed for HDL cholesterol., Conclusions: Diabetes is associated with a reduced exercise capacity in patients with HF. Most predictors of lower exercise capacity in HF are similar regardless of DM except impaired vascular function and lower HDL cholesterol which predict lower exercise capacity only in those with DM., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Stefan Anker reports a relationship with CSL Vifor that includes: consulting or advisory and funding grants. Stefan Anker reports a relationship with Bayer AG that includes: consulting or advisory. Stefan Anker reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory. Stefan Anker reports a relationship with Servier that includes: consulting or advisory. Stefan Anker reports a relationship with Abbott Vascular Inc that includes: consulting or advisory and funding grants. Stefan Anker reports a relationship with Cardiac Dimensions Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Actimed Therapeutics that includes: consulting or advisory. Stefan Anker reports a relationship with AstraZeneca that includes: consulting or advisory. Stefan Anker reports a relationship with Amgen Inc that includes: consulting or advisory. Stefan Anker reports a relationship with BioVentrix Inc that includes: consulting or advisory. Stefan Anker reports a relationship with V-Wave Ltd that includes: consulting or advisory. Stefan Anker reports a relationship with Brahms that includes: consulting or advisory. Stefan Anker reports a relationship with Cordio that includes: consulting or advisory. Stefan Anker reports a relationship with Occlutech GmbH that includes: consulting or advisory. Stefan Anker reports a relationship with Cardior that includes: consulting or advisory. Stefan Anker reports a relationship with CVRx Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Cytokinetics Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Edwards that includes: consulting or advisory. Stefan Anker reports a relationship with Farraday Pharmaceuticals that includes: consulting or advisory. Stefan Anker reports a relationship with GSK that includes: consulting or advisory. Stefan Anker reports a relationship with HeartKinetics that includes: consulting or advisory. Stefan Anker reports a relationship with Impulse Dynamics that includes: consulting or advisory. Stefan Anker reports a relationship with Pfizer Inc that includes: consulting or advisory. Stefan Anker reports a relationship with Repairon that includes: consulting or advisory. Stefan Anker reports a relationship with Medical Sensible that includes: consulting or advisory. Stefan Anker reports a relationship with Vectorious that includes: consulting or advisory. John GF Cleland reports a relationship with British Heart Foundation that includes: board membership and funding grants. John GF Cleland reports a relationship with Pharmacosmos, Inc. that includes: consulting or advisory, funding grants, and travel reimbursement. John GF Cleland reports a relationship with CSL-Vifor that includes: funding grants. John GF Cleland reports a relationship with Abbott Vascular Inc that includes: consulting or advisory. John GF Cleland reports a relationship with Biopeutics that includes: consulting or advisory and travel reimbursement. John GF Cleland reports a relationship with Medtronic Inc that includes: board membership. John GF Cleland reports a relationship with Deputy Editor of European Heart Journal that includes: board membership. Stephan von Haehling reports a relationship with Amgen Inc that includes: funding grants. Stephan von Haehling reports a relationship with AstraZeneca that includes: consulting or advisory, funding grants, and speaking and lecture fees. Stephan von Haehling reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory, funding grants, and speaking and lecture fees. Stephan von Haehling reports a relationship with Pharmacosmos, Inc. that includes: consulting or advisory, funding grants, and speaking and lecture fees. Stephan von Haehling reports a relationship with IMI that includes: funding grants. Stephan von Haehling reports a relationship with German Center for Cardiovascular Research (DZHK) that includes: funding grants. Stephan von Haehling reports a relationship with BRAHMS that includes: consulting or advisory. Stephan von Haehling reports a relationship with MSD that includes: consulting or advisory. Stephan von Haehling reports a relationship with Novo Nordisk Inc that includes: consulting or advisory and speaking and lecture fees. Stephan von Haehling reports a relationship with Novartis that includes: consulting or advisory and speaking and lecture fees. Stephan von Haehling reports a relationship with Pfizer that includes: consulting or advisory. Stephan von Haehling reports a relationship with Respicardia that includes: consulting or advisory. Stephan von Haehling reports a relationship with Roche that includes: consulting or advisory. Stephan von Haehling reports a relationship with Servier that includes: consulting or advisory. Stephan von Haehling reports a relationship with Vifor that includes: consulting or advisory and speaking and lecture fees. Stephan von Haehling reports a relationship with Bayer AG that includes: speaking and lecture fees. Stephan von Haehling reports a relationship with Edwards Lifesciences Corporation that includes: speaking and lecture fees. Stephan von Haehling reports a relationship with Amomed Pharma GmbH that includes: consulting or advisory. Stephan von Haehling reports a relationship with Actimed that includes: equity or stocks. Wolfram Doehner reports a relationship with Vifor that includes: consulting or advisory and funding grants. Wolfram Doehner reports a relationship with Boehringer Ingelheim GmbH that includes: board membership, consulting or advisory, and funding grants. Wolfram Doehner reports a relationship with Aimediq that includes: consulting or advisory. Wolfram Doehner reports a relationship with AstraZeneca that includes: consulting or advisory. Wolfram Doehner reports a relationship with Bayer AG that includes: consulting or advisory. Wolfram Doehner reports a relationship with Boston Scientific Corp that includes: consulting or advisory. Wolfram Doehner reports a relationship with Medtronic that includes: consulting or advisory. Wolfram Doehner reports a relationship with Cardiomatics that includes: consulting or advisory. Wolfram Doehner reports a relationship with ICON Clinical Research LLC that includes: consulting or advisory. Wolfram Doehner reports a relationship with Pharmacosmos, Inc. that includes: travel reimbursement. Wolfram Doehner reports a relationship with IQVIA that includes: board membership. Wolfram Doehner reports a relationship with European Society of cardiology (ESC) that includes: board membership. Wolfram Doehner reports a relationship with ESC Council on Stroke that includes: board membership. Wolfram Doehner reports a relationship with Society of cachexia and wasting disorders that includes: board membership. Ewa A. Jankowska reports a relationship with Vifor Pharma that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Pharmacosmos, Inc. that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Novartis that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Novo Nordisk that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with AstraZeneca that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Boehringer Ingelheim that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Pfizer that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Zoll that includes: board membership and consulting or advisory. Ewa A. Jankowska reports a relationship with Respicardia that includes: board membership and consulting or advisory. Ewa A. Jankowska reports a relationship with Bayer that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Abbott that includes: board membership, consulting or advisory, and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Cardiac Dimensions Inc that includes: board membership and consulting or advisory. Ewa A. Jankowska reports a relationship with Amicus that includes: consulting or advisory. Ewa A. Jankowska reports a relationship with Swixx Biopharma that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Ewopharma that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Servier that includes: board membership and speaking and lecture fees. Ewa A. Jankowska reports a relationship with Takeda that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Sanofi that includes: speaking and lecture fees. Ewa A. Jankowska reports a relationship with Executive Committee of the HFA Board 2016–2022 that includes: board membership. Miroslava Valentova reports a relationship with Bayer that includes: speaking and lecture fees. Stefan Anker has patent #MR-proANP (DE 102,007,010,834 & DE 102007022367) issued to BRAHMS. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Individuals with Multiple Sclerosis (MS) experience impairments in heat dissipation, compromising core temperature regulation during exercise., Objective: To examine the efficacy of combined head-and-neck cooling as administered via a commercially available cooling cap and neck wrap in mitigating increases in core temperature during exercise., Methods: On separate days, ten (7 females) adults (46.1 ± 11.6 years) with relapsing-remitting MS performed semi-recumbent cycling consisting of an incremental exercise bout to volitional fatigue in a temperate environment (23 °C, 50 % relative humidity) while undergoing head-and-neck cooling using a cooling cap and neck wrap maintained at 10 °C (COLD) or 24-26 °C (NEUTRAL). Prior to and following a 30-minute post-exercise recovery, functional capacity was assessed by a battery of tests consisting of a 2-minute walk test, Timed 25-Foot Walk test, sit-to-stand test, and Berg Balance Scale. Core (ingestible pill) and skin temperatures were recorded continuously. The level of fatigue was measured with questionnaires., Results: The duration of the incremental exercise test increased with the application of COLD (28.4 ± 5.1 min) versus NEUTRAL water (vs 20.8 ± 5.1 min) (p = 0.001) and was paralleled by a significant reduction in body temperatures (∼1 °C, p < 0.05). The distance covered during the 2-min walk test performed after the incremental exercise test increased with the COLD (176.5 ± 0.6 m), relative to the NEUTRAL condition (147.7 ± 43.5 m) (p = 0.01). Fatigue levels did not change between conditions., Conclusion: We show that head-and-neck cooling with cold water effectively enhances exercise tolerance and mitigates increases in core temperature during exercise in individuals with MS., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Importance: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures., Objective: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates., Design, Setting, and Participants: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO2] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024., Interventions: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks., Main Outcomes and Measures: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO2 and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO2] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed., Results: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory-validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, -0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P <.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P <.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO2 were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO2 and VE/VCO2 slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P <.05)., Conclusions and Relevance: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten., Trial Registration: ClinicalTrials.gov Identifier: NCT05186818.

Background: Considering the limitations in activities of daily living (ADL) and the impact of improvements in patients with heart failure (HF), appropriate assessment of upper extremity functional capacity and ADL is important., Objectives: To evaluate upper extremity functional capacity and ADL in patients with HF and compare them with healthy controls., Methods: This study included 30 HF patients and healthy controls. Upper extremity functional capacity was assessed with the 6-Minute Pegboard Ring Test (6PBRT), ADL by the Londrina protocol, exercise capacity by 6-Minute Walk Test (6MWT), peripheral muscle strength by hand dynamometer, and dyspnea by Modified Medical Research Council Scale (MMRC). For performance tests, pre-test (resting) and post-test (after performance) values ​​were also measured., Results: Patients with HF with ejection fraction ≤50 % and controls were similar in terms of age (52.63±6.2 and 50.03±6.5 years, respectively) and gender (25 females for each group) (p > 0.05). Patients showed a statistically significant increase in total test time in the Londrina protocol and fewer rings moved in 6PBRT (p < 0.0001). The post-test dyspnea (p = 0.03) and pre-test arm fatigue (p < 0.0001) were observed to be higher in patients in the Londrina protocol. There was a statistically significant group by time interaction in the patients' pre- and post-test lower heart rate (F= 4.80, p = 0.03), post-test dyspnea (p < 0.0001), and post-test arm fatigue (p = 0.005) were observed to be higher in patients in 6PBRT., Conclusions: The evidence showed a decrease in upper extremity functional capacity in patients with HF. Patients required more time to perform their ADLs compared with healthy controls., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Patients with cystic fibrosis (CF) experience increased oxidative stress. Tele-exercise can be a new method to improve exercise in CF., Objective: This study aimed to investigate the effect of telehealth-based exercise training using different modalities (combined exercise training group, CombG, core stabilization exercise group, SG), in comparison with control group (CG), on exercise capacity, oxidative stress, and irisin in children with CF., Methods: Thirty-nine children with CF (mean age=11.41±2.18 years, mean FEV 1 (z-score)=-0.66±1.96) were included in the study. The children were randomly allocated to groups. The CombG and SG performed core stabilization exercises (CS) 3 days per week for 8 weeks. The CombG also performed aerobic exercises 3 days per week in addition to CS. Physical activity (PA) recommendations were provided to the CG. Exercise capacity was evaluated using the Modified Shuttle Test (MST). Oxidative stress was assessed using total antioxidant status (TAS), total oxidant status (TOS), Oxidative Stress Index (OSI), malondialdehyde (MDA), and superoxide dismutase (SOD). The irisin level was also measured., Results: Children's baseline sex, age, BMI, and FEV 1 z-scores were similar (p > 0.05). The MST distance (p = 0.047,np 2 =0.157) and%MST distance (p = 0.045, np 2 =0.159) significantly improved in the CombG compared with the SG and CG. Although TAS and SOD decreased over time (p < 0.05), no significant changes were observed for TAS, TOS, OSI, MDA, SOD, and irisin parameters between the groups after training (p > 0.05)., Conclusions: Combining aerobic exercise training with core stabilization applied using telehealth improved exercise capacity more than core stabilitation training only or PA recommendations in children with CF., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Invasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI., Methods: We included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise., Results: Among 84 patients, PI was identified in 57 (67.8 %). Compared to patients without PI, those with PI were younger [median (IQR) 37 (28, 46) vs 47 (39,55) years, p = 0.005] and had lower workload at peak exercise [81 (66, 96) vs 95 (83.5, 110.50) Watts, p = 0.006]. Patients with PI had higher heart rates at rest and peak exercise [87 (78, 97) vs 79 (74, 87) bpm, p = 0.04; and 167 (154, 183) vs 156 (136, 168) bpm, p = 0.01, respectively]. In all patients, epinephrine and norepinephrine at peak exercise directly correlated with peak workload (r:0.41, p < 0.001 and r:0.47, p < 0.001, respectively). Resting epinephrine was higher in patients with PI [136 (60, 210) vs 77 (41, 110) pg/mL, p = 0.02]. There was no significant difference in the change in catecholamines from rest to peak exercise between patients with or without PI., Conclusion: PI patients exhibited elevated heart rate and epinephrine at rest, indicating increased sympathetic activity. We did not find strong associations between catecholamines and cardiac filling pressures, suggesting that catecholamine levels are predominantly influenced by peak workload., Competing Interests: Declaration of competing interest The authors have no significant conflicts of interest with any companies or organizations whose products or services may be discussed in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The Chester Step Test (CST) is a simple and inexpensive field test, which requires minimal physical space to assess exercise capacity. Such characteristics make the CST suitable to be used in different settings, however, its measurement properties in patients with interstitial lung diseases (ILD) are unknown., Methods: A cross-sectional study was conducted in patients with ILD. First, a CST-1 and a 6-minute walk test (6MWT) were performed. After 48-72 hours, a CST-2 was repeated. A 2nd rater was present in one of the sessions. Relative reliability was measured using intraclass correlation coefficient (ICC 1,1 and ICC 2,1 ). Absolute reliability was determined using standard error of measurement (SEM), minimal detectable change at 95% confidence interval (MDC 95 ) and the Bland-Altman method. The values of SEM and MDC 95 were also expressed as a percentage of the mean. Construct validity was explored using Spearman correlation coefficient (r s ) between the number of steps taken in the best CST and the distance performed in the 6MWT., Results: Sixty-six patients with ILD (65.5±12.9 years; 48.5%men; FVC 79.4±18.8pp; DL CO 49.0±18.3pp) participated in the study. Relative (ICC 0.95-1.0) and absolute reliability were excellent without evidence of systematic bias. The SEM and MDC 95 were 11.8 (14.7%) and 32.6 steps (40.7%), respectively. The correlation between CST and 6MWT was significant, positive, and high (r s =0.85, p=0.001)., Conclusion: The CST is a reliable and valid test and might be especially useful to assess exercise capacity in patients with ILD in limited space environments., Competing Interests: Conflicts of interest The authors report no financial, or non-financial, conflicts of interest in this work., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Aeorobic exercise is an essential component of the pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease (COPD). Single-limb exercises are a type of aeorobic exercise that aims to increase patient tolerance by reducing the workload of the respiratory system., Objektives: The aim of our systematic review was to determine the effects of single-limb exercises on pulmonary function, dyspnea, fatigue, and muscle dysfunction in patients with COPD., Methods: Searches were performed using PubMed, Pedro, Google Scholar, MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science databases. Publications from the beginning to 2023 searched. Studies were selected by two authors by scanning the title, Mesh terms abstract in Rayyan QCRI software. Selected studies were subjected to full-text screening by applying selection criteria. Randomized controlled, case-control, cohort studies were included., Results: In the first screening according to mesh terms, 1011 articles were identified. After the screening criteria and duplicate articles were evaluated, 10 articles were included. This systematic review includes seven case-control, one randomized control trial (RCT), one cross-sectional, and one non-randomized study. A total of 157 patients with COPD received treatment in these studies. According to the Bakker scale, single-limb exercises have been shown to improve pulmonary function with strong evidence. There is strong evidence that single-limb exercises have no effect on dyspnea and fatigue in COPD patients. There is limited evidence that single-limb exercises have an effect on functional exercise capacity., Conclusion: Single-limb exercise can advised in terms of improving pulmonary function in patients with COPD. Current systematic review has found single limb exercise has no effect on dyspnea and fatigue perception. No side effects were reported in the studies and these exercises can be considered safe., Competing Interests: Declaration of competing interest There is no conflict of interest current study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Delayed-onset muscle soreness (DOMS) has been widely examined in the peripheral muscles; however, studies showing the potential effects of DOMS on respiratory function are limited., Hypothesis: DOMS in trunk muscles has a negative effect on respiratory function parameters, respiratory muscle strength, respiratory muscle endurance, and exercise capacity., Study Design: Prospective cohort study., Level of Evidence: Level 2., Methods: In 24 healthy participants with a mean age of 21 ± 2 years, DOMS was induced for the trunk muscles with a load equal to 80% of the maximum repetitive voluntary contraction. Pulmonary function parameters, respiratory muscle strength and endurance, exercise capacity, pain, fatigue, and dyspnea perception severity were recorded before DOMS and at 24 and 48 hours after DOMS., Results: After DOMS, decreases were observed in respiratory function parameters, namely, forced vital capacity, forced expiratory volume in the first second, vital capacity, and 25% to 75% flow rate value of forced expiratory volume (25% to 75%) ( P = 0.02, P = 0.02, P < 0.01, P = 0.01, respectively). Maximal inspiratory pressure and exercise capacity also decreased ( P = 0.02, P < 0.01, respectively). No difference was observed between all 3 measurements of maximal expiratory pressure (MEP) and MEP% values ( P 1 = P 2 = P 3 ≥ 0.99). The results of the respiratory muscle endurance tests did not reveal a significant difference in terms of load and time in all 3 conditions ( P > 0.05)., Conclusion: After DOMS, there was a 4% to 7.5% decrease in respiratory function parameters, and a 6.6% decrease in respiratory muscle strength., Clinical Relevance: The occurrence of DOMS before a competition can have a detrimental impact on pulmonary performance. Hence, it is imperative to consider this factor when devising training and exercise programs. In addition, the development of treatment protocols becomes crucial if DOMS arises., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Background: The cardiopulmonary exercise test (CPET) is the gold standard for assessing aerobic fitness; however, it is expensive, not widely available, and requires specialized equipment and staff. The incremental shuttle walking test (ISWT) is an exercise field test used to evaluate exercise capacity and may be an alternative to CPET in patients with lymphangioleiomyomatosis (LAM)., Objective: To investigate whether the ISWT can be used to assess maximal aerobic capacity in patients with LAM., Methods: Forty-five women were evaluated on two days, and they randomly performed the CPET and ISWT. The maximum oxygen uptake (peak VO 2 ) was evaluated using gas analyzers in both tests. The carbon dioxide production (VCO 2 ), respiratory exchange ratio (RER), and heart rate (HR) were compared during peak exercise. Pearson's correlation and Bland-Altman assessed the association and agreement, respectively. The intraclass correlation coefficient (ICC) was used to assess the reliability of the data., Results: All patients (46.1 ± 10.2 years) presented similar peak VO 2 , RER, and peak HR during the CPET and ISWT (15.6 ± 4.6 vs. 15.7 ± 4.4 ml·kg -1 ·min -1 ; 1.15±0.09 vs. 1.17±0.12; and 142.2 ± 18.6 vs. 141.5 ± 22.2 bpm, respectively; p>0.05). A good linear correlation (r = 0.79; p<0.001) and ICC (0.86; 95%CI 0.74-0.93) were observed between the peak VO 2 in both tests. Predictive peak VO 2 equations based on the ISWT performance are also presented., Conclusion: Our results suggest that the ISWT can be used to assess maximal exercise performance in patients with LAM, and it is a valuable option to be used as an alternative to the CPET and predict maximal exercise capacity., Competing Interests: Declaration of Competing Interest The authors declare having no conflicts of interest to disclose., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: In patients with chronic obstructive pulmonary disease (COPD), the clinical use of the minute ventilation-carbon dioxide production ([Formula: see text] E -[Formula: see text] CO2 ) slope has been reported as a measure of exercise efficiency, but the oxygen uptake efficiency slope (OUES), i.e., the slope of oxygen uptake ([Formula: see text] O2 ) versus the logarithmically transformed [Formula: see text] E , has rarely been reported., Methods: We hypothesized that the [Formula: see text] E -[Formula: see text] CO2 slope is more useful than OUES in clinical use for the pathophysiological evaluation of COPD. Then, we investigated the cardiopulmonary exercise testing parameters affecting each of these slopes in 122 patients with all Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD grades selected from our database., Results: Compared with the GOLD I-II group (n = 51), peak [Formula: see text] O2 (p < 0.0001), OUES (p = 0.0161), [Formula: see text] E at peak exercise (p < 0.0001), and percutaneous oxygen saturation (SpO 2 ) at peak exercise (p = 0.0004) were significantly lower in the GOLD III-IV group (n = 71). The GOLD III-IV group was divided into two groups by the exertional decrease in SpO 2 from rest to peak exercise: 3% or less (the non-desaturation group: n = 23), or greater than 3% (the desaturation group: n = 48). OUES correlated only weakly with peak [Formula: see text] O2 , [Formula: see text] E at peak exercise, and the difference between inspired and expired mean O 2 concentrations (ΔF O2 ) at peak exercise, i.e., an indicator of oxygen consumption ability throughout the body, in the GOLD III-IV group with exertional hypoxemia. In contrast, the [Formula: see text] E -[Formula: see text] CO2 slope was significantly correlated with ΔF O2 at peak exercise, regardless of the COPD grade and exertional desaturation. Across all COPD stages, there was no correlation between the [Formula: see text] E -[Formula: see text] CO2 slope and [Formula: see text] E at peak exercise, and stepwise analysis identified peak [Formula: see text] O2 (p = 0.0345) and ΔF O2 (p < 0.0001) as variables with a greater effect on the [Formula: see text] E -[Formula: see text] CO2 slope., Conclusions: The OUES may be less useful in advanced COPD with exertional hypoxemia. The [Formula: see text] E -[Formula: see text] CO2 slope, which is independent of [Formula: see text] E , focuses on oxygen consumption ability and exercise tolerance in COPD, regardless of the exertional hypoxemia level and COPD grade. Therefore, the [Formula: see text] E -[Formula: see text] CO2 slope might be useful in establishing or evaluating tailor-made therapies for individual patient's pathologies in COPD as an indicator focusing on oxygen consumption ability., (© 2024. The Author(s).)

Background: The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD., Methods: This double-blind, randomised, active- and placebo-controlled, crossover study recruited adults with COPD aged ≥ 40 years, who were hyperinflated and symptomatic, and were receiving mono- or dual inhaled maintenance COPD therapy. In the three treatment periods, patients were randomised to receive BDP/FF/G, BDP/FF, or placebo, each for 3 weeks, with a 7-10-day washout between treatment periods. Assessments included slow inspiratory spirometry (for resting inspiratory capacity [IC]) and constant work-rate cycle ergometry (for dynamic IC and exercise endurance time). The primary objective was to compare BDP/FF/G and BDP/FF vs. placebo for resting IC at Week 3. Key secondary objectives were to compare BDP/FF/G and BDP/FF vs. placebo for dynamic IC and exercise endurance time during constant work rate cycle ergometry at Week 3., Results: Of 106 patients randomised, 95 completed the study. Resting IC adjusted mean differences vs. placebo were 315 and 223 mL for BDP/FF/G and BDP/FF, respectively (p < 0.001 for both). Adjusted mean differences vs. placebo for the key secondary endpoints were: 245 mL for dynamic IC (p < 0.001) and 69.2 s for exercise endurance time (nominal p < 0.001) with BDP/FF/G, and 96 mL (p = 0.053) and 70.1 s (nominal p < 0.001) with BDP/FF. Differences between BDP/FF/G and BDP/FF for resting and dynamic IC were 92 and 149 mL (p < 0.01 for both). All three treatments were generally well tolerated, with 27.3%, 25.3% and 19.0% of patients reporting adverse events with BDP/FF/G, BDP/FF and placebo, respectively, all mild or moderate., Conclusions: In patients with COPD, BDP/FF/G provided significant and clinically relevant improvements vs. placebo and BDP/FF in static and dynamic hyperinflation, with an improvement vs. placebo in exercise endurance., Trial Registration: ClinicalTrials.gov (NCT05097014), registered 27th October 2021., (© 2024. The Author(s).)

Background and Aims: Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF)., Methods: FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL)., Results: The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5-93; P = .029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07-0.96; P = .043) was lower with FCM than placebo., Conclusions: In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Marfan syndrome (MFS) is a genetic disorder affecting the vascular and musculoskeletal systems. Limited knowledge exists regarding the exercise benefits for this population. This study aimed to explore the impact of a structured exercise program on the quality of life (QoL) and physical capabilities of patients with MFS., Methods and Results: This was a randomized, controlled, parallel-group trial. Patients with MFS were randomized in a 1:1 ratio to either a training group or a control group. The trial included a 3-month online supervised training program. Seventy patients with MFS were compared with healthy subjects. They were randomized into a training group (MFS-T) and a control group (MFS-C). The training consisted of 2 supervised online sessions weekly for 3 months. The primary outcome was QoL, assessed using the Medical Outcomes Study Short-Form 36 questionnaire. Baseline QoL in all dimensions was lower in patients with MFS. Their peak oxygen uptake was 25% lower, and muscle elasticity was diminished compared with healthy subjects. Postintervention, significant improvements were observed in the MFS-T group relative to the MFS-C group: QoL (+20.2±14.3 versus +0.7±0.5), peak oxygen uptake (+34% versus +14%), muscle elasticity index (11.5±8.2 versus +1.2±1.7), reduced blood pressures during isometric squats (systolic -19±30 versus 0±6; diastolic -27±39 versus +2±15), and reduced pulse wave velocity at rest (-1.20±1.89 versus -0.40±1.61) and postexercise (-0.42±0.45 versus +0.08±0.48). The aortic diameter remained stable in both groups (MFS-T-0.19±1.1 versus MFS-C+0.11±0.78). After training, QoL remained lower in MFS-T than in healthy subjects, but peak oxygen uptake, pulse wave velocity at rest, and postexercise were similar to those of healthy subjects., Conclusions: The 3-month online training program significantly enhanced QoL and cardiovascular/muscular metrics in patients with MFS without affecting aortic root diameter, suggesting its potential as part of a management strategy for MFS., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04553094.

Sickle cell disease (SCD) is characterized by central (cardiac) and peripheral vascular dysfunctions, significantly diminishing exercise capacity and quality of life. Although central cardiopulmonary abnormalities in SCD are known to reduce exercise capacity and quality of life; the impact of hemolysis and subsequent cell-free hemoglobin (Hb)-mediated peripheral vascular abnormalities on those outcomes are not fully understood. Despite the recognized benefits of exercise training for cardiovascular health and clinical management in chronic diseases like heart failure, there remains substantial debate on the advisability of regular physical activity for patients with SCD. This is primarily due to concerns that prolonged and/or high-intensity exercise might trigger metabolic shifts leading to vaso-occlusive crises. As a result, exercise recommendations for patients with SCD are often vague or nonexistent, reflecting a gap in knowledge about the mechanisms of exercise intolerance and the impact of exercise training on SCD-related health issues. This mini-review sheds light on recent developments in understanding how SCD affects exercise tolerance, with a special focus on the roles of hemolysis and the release of cell-free hemoglobin in altering cardiovascular and skeletal muscle function. Also highlighted here is the emerging research on the therapeutic effects and safety of exercise training in patients with SCD. In addition, the review identifies future research opportunities to fill existing gaps in our understanding of exercise (in)tolerance in SCD.

Near-infrared spectroscopy (NIRS) can be used to demonstrate muscle metabolism and oxygenation. NIRS-based oximeters enable the noninvasive measurement of static and dynamic muscle oxygenation. This study aimed to evaluate the relationship between NIRS readings and exercise capacity in group E COPD patients. The prospective study included 40 patients with group E COPD who presented to our outpatient clinic between May 2021 and June 2022. The patients were evaluated with pulmonary function testing, 6-Minute Walk Test (6MWT), echocardiography, and dyspnea and quality of life assessments. NIRS muscle oxygen saturation (SmO 2 ) levels at the start and end of the 6MWT were obtained. 6MWT distance was positively correlated with intercostal SmO 2 and fingertip SO 2 at the start (R = 0.679, p ≤ 0.001 and R = 0.321, p = 0.04, respectively) and end of the 6MWT (R = 0.693, p ≤ 0.001 and R = 0.635, p ≤ 0.001, respectively) and negatively correlated with the number of hospitalizations due to exacerbations in the last year and mean pulmonary arterial pressure (R =  - 0.648, p ≤ 0.001 and R =  - 0.676, p ≤ 0.001, respectively). SF-36 score was positively correlated with intercostal SmO 2 at the beginning of the 6MWT (R = 0.336, p = 0.03). Intercostal SmO 2 levels at the start of the 6MWT positively correlated with diffusing capacity of the lung for carbon dioxide (DLCO) (R = 0.388, p = 0.01) and ratio of DLCO to alveolar volume (DLCO/VA) levels (R = 0.379, p = 0.02), and these correlations persisted more strongly after the 6MWT (R = 0.524, p = 0.01; R = 0.500, p = 0.01, respectively). NIRS is a practical and noninvasive method for measuring muscle oxygenation and can be used as an alternative to 6MWT in the evaluation of exercise capacity in patients with group E COPD., (© 2024. The Author(s).)

Aims: Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non-cardiac dyspnoea (NCD), and healthy volunteers., Methods and Results: Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom-limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P = 0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P < 0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P < 0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52 W (interquartile range 31-73), 150 W (125-175), P < 0.001], but not NCD [53 W (33, 75), P = 0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08 mmol/L/W (0.05-0.11), 0.06 mmol/L/W (0.05-0.08; P = 0.016) in NCD, and 0.04 mmol/L/W (0.03-0.05; P < 0.001) in volunteers. Exercise cardiac index was 4.5 L/min/m 2 (3.7-5.5) in HFpEF, 5.2 L/min/m 2 (4.3-6.2; P < 0.001) in NCD, and 9.1 L/min/m 2 (8.0-9.9; P < 0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553 mL/min (1175-1986) vs. 1758 mL/min (1361-2282; P = 0.024) in NCD and 3117 mL/min (2667-3502; P < 0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P < 0.001)., Conclusions: HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: This study aimed to investigate the respiratory physiological changes resulting from short-term inspiratory resistance training (R-IMT) and inspiratory threshold training (T-IMT) in patients with chronic obstructive pulmonary disease (COPD) and to compare the mechanisms of the two training methods., Patients and Methods: A total of 75 stable patients with COPD combined with inspiratory muscle weakness were randomly allocated to three groups: R-IMT (n = 26), T-IMT (n = 24), and control (n = 25). Before and after 8 weeks of inspiratory muscle training(IMT), cardiopulmonary exercise tests were conducted to assess respiratory patterns, respiratory central drive, exercise tolerance, and ventilation efficiency., Results: After 8 weeks of IMT, Inspiratory muscle strength, represented by MIP (maximum inspiratory mouth pressure) and exercise capacity increased during exercise in both IMT groups (P < 0.05). In the R-IMT group, inspiratory time (Ti) prolonged (P < 0.05), tidal volume (Vt) increased (P < 0.05), ventilation efficiency (represented by ventilation-center coupling) increased (P < 0.05) during exercise. Conversely, the T-IMT group did not exhibit any of these changes after IMT (P > 0.05)., Conclusion: In summary, the improvement in exercise tolerance was associated with an increase in inspiratory muscle reserve in both R-IMT and T-IMT. However, only R-IMT was associated with deeper and slower breathing, as well as improved ventilation efficiency., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Many studies evaluated the functional response in post-Covid-19 patients; however, they systematically excluded patients with concomitant acute coronary syndrome (ACS). We evaluated the long-term functional capacity assessed by cardiopulmonary exercise test (CPET) in patients hospitalized for ACS and concomitant SARS-CoV2 infection. The secondary aim was to investigate the functional response in patients with symptoms related to "long COVID-19 syndrome" (LCS)., Methods: This cross-sectional case-control study compared 20 patients with ACS and concomitant SARS-COV2 infection with 20 patients without COVID-19. At the follow-up visit (between 6 and 12 months after revascularization procedure) all patients underwent a CPET., Results: Patients with previous ACS and concomitant COVID-19 showed a reduced O2 consumption than controls (predicted peak V̇O2 74.00% vs 86.70%; p = 0.01) with a high degree of ventilatory inefficiency (VE/ V̇CO2 slope 38.04 vs 30.31; p = 0.002). 50% of subjects with previous COVID-19 disease showed symptoms related to "LCS"; this subgroup demarcates the characteristic reduced exercise capacity found in the entire COVID + group., Conclusions: This study is the first in literature having analyzed the long-term functional capacity phenotype in a population of ACS patients and concomitant SARS-CoV2 infection. Severe ventilatory inefficiency emerged as the functional signature of these patients. Moreover, the subset of patients with symptoms related to LCS has the most compromised long term reduced exercise capacity and an altered ventilation control., Competing Interests: Declaration of Competing Interest We declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Published by Elsevier B.V.)

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6-12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm 2 /m 2 ). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO 2 ). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO 2 post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO 2 post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO 2 , the gold standard measure of aerobic exercise capacity., (© 2024. The Author(s).)

Background: Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver-synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin-A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin-A in connecting cardiac-hepatic-peripheral interaction., Methods and Results: We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin-A by ELISA. Correlation analysis revealed a negative association between fetuin-A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin-A levels. During a median follow-up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high-risk subgroup with lower fetuin-A (<24.3 mg/L) and impaired exercise tolerance (peak oxygen uptake<14.2 mL/kg per min). Kaplan-Meier analysis revealed that this subgroup had the highest risk of cardiac events. In a multivariable Cox proportional hazard model, the combination of lower fetuin-A and exercise intolerance was independently associated with increased risks of cardiac events., Conclusions: Reduced circulating fetuin-A levels were associated with exercise intolerance in heart failure patients. Fetuin-A could emerge as a target implicated in exercise capacity connecting cardiac-hepatic-peripheral interaction and as a valuable biomarker for predicting prognosis when combined with peak oxygen uptake.

People with end-stage kidney disease (ESKD) often exhibit impaired cardiac structure and function, which may contribute to poor exercise capacity. This study used multimodal exercise testing to investigate the central and peripheral mechanisms of exercise limitation in adults with ESKD, also comparing in-centre hemodialysis (ICHD) to home hemodialysis (HHD). Seventeen adults (55.5 ± 14.5 years; n = 14 male; n = 12 HHD) participated. Resting cardiac examinations, followed by submaximal cycling cardiopulmonary exercise testing (CPET) and functional exercise testing, revealed cardiac structural abnormalities (increased left ventricular mass) and cardiac injury. Aerobic fitness in adults with ESKD was low, with pulmonary oxygen uptake (V̇O 2 ) at the gas exchange threshold (GET) occuring at 39 ± 8% predicted V̇O 2peak . O 2 pulse, an estimate of stroke volume (SV), was higher in HHD at rest (p = 0.05, ES = 0.58) and during unloaded cycling (p = 0.05, ES = 0.58) compared to ICHD. However, thoracic bioreactance derived SV at the GET was significantly higher in adults receiving ICHD versus HHD (p = 0.01, ES = 0.74). In adults with ESKD, cardiac output was positively associated with V̇O 2 at the GET (r = 0.61, p = 0.04). This study highlights prevalent exercise dysfunction in adults with ESKD undergoing dialysis, with potential distinct differences between in-centre and home hemodialysis, mechanistically linked to underlying cardiac abnormalities., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary aim to examine the relationship between symptom-based clinical profiles and recovery., Methods: Prospective observational study of adults aged 18 to 65 years who had sustained mTBI within the previous 7 days. Symptoms were assessed using the Post-Concussion Symptom Scale, HR was measured at rest, and exercise tolerance was assessed using the Buffalo Concussion Bike Test. Symptom burden and symptom-based clinical profiles were examined with respect to exercise tolerance and resting HR., Results: Data from 32 participants were assessed (mean age 36.5 ± 12.6 years, 41% female, 5.7 ± 1.1 days since injury). Symptom burden (number of symptoms and symptom severity) was significantly associated with exercise intolerance ( P = .002 and P = .025, respectively). Physiological and vestibular-ocular clinical profile composite groups were associated with exercise tolerance ( P = .001 and P = .014, respectively), with individuals who were exercise intolerant having a higher mean number of symptoms in each profile than those who were exercise tolerant. Mood-related and autonomic clinical profiles were associated with a higher resting HR (>80 bpm) ( P = .048 and P = .028, respectively), suggesting altered autonomic response for participants with symptoms relating to this profile. After adjusting for age and mechanism of injury (sports- or non-sports-related), having a higher mood-related clinical profile was associated with persisting symptoms at 3 months postinjury (adjusted odds ratio = 2.08; 95% CI, 1.11-3.90; P = .013)., Conclusion: Symptom-based clinical profiles, in conjunction with objective measures such as resting HR and exercise tolerance, are important components of clinical care for those having sustained mTBI. These results provide preliminary support for the concept that specific symptoms are indicative of autonomic dysfunction following mTBI., Competing Interests: Competing interests: Prof Melinda Fitzgerald declares her role as CEO of Connectivity Traumatic Brain Injury Australia Ltd. Dr Gill Cowen declares her role as Chairperson of the Western Australian Concussion Network. All other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking., Objective: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF., Methods: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded., Results: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model., Conclusion: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review synthesizes the expanding evidence for pulmonary rehabilitation that has led to its recommended inclusion in the holistic care of people with idiopathic pulmonary fibrosis (IPF), as well as discussing strategies that may maximize and sustain benefits., Recent Findings: Pulmonary rehabilitation is an effective intervention leading to significant improvements in exercise tolerance, symptoms, and quality of life for people with IPF. Improvements in symptoms and quality of life can persist longer term, whereas functional capacity does not; therefore, strategies to preserve functional capacity are an important area of research. Referral early in the disease course is encouraged to promote longer lasting effects. Evidence that high-intensity interval training may optimize benefits of exercise training is emerging. Supplemental oxygen is frequently used to manage exercise-induced desaturation, although its use as an adjunct therapy requires more evidence., Summary: Current evidence strongly supports the inclusion of pulmonary rehabilitation in the standard holistic care of IPF, with early participation encouraged. Further research is needed to establish the optimal exercise strategies, modalities and adjunct therapies that enhance outcomes of pulmonary rehabilitation and promote longer lasting effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypertensive heart disease (HHD) is a leading contributor to heart failure with preserved ejection fraction (HFpEF). However, the mechanisms behind the transition to the symptomatic phase remain unclear., Objectives: We sought to find the association of the exercise response of left atrial (LA) mechanical function with functional capacity, symptoms, and outcome across the heart failure (HF) spectrum in hypertension., Methods: Echocardiography (including LA reservoir peak atrial longitudinal strain [PALS] and peak atrial contractile strain [PACS] and LA stiffness index) was performed at rest and immediately postexercise in 139 patients with HHD-35 with stage A, 48 with stage B, and 56 with stage C HFpEF. Patients were followed for HF and atrial fibrillation., Results: Exercise capacity was progressively worse from stage A through stage B to stage C and was accompanied by a gradual impairment of changes in PALS and PACS from rest to exercise, whereas LA stiffness reserve remained unchanged until stage C. Peak atrial longitudinal strain and PACS reserves were independently associated with exercise capacity (P = .017 and .008, respectively). Left atrial stiffness reserve and E/e' were the strongest associations of symptomatic HF. Over a median of 25 months, 35 patients developed HF and/or atrial fibrillation. Peak atrial longitudinal strain and PACS reserves were associated with the study end points after adjusting for age, diabetes, N-terminal pro-B type natriuretic peptide, LA volume index, resting E/e', and resting PALS/PACS., Conclusions: Impaired exercise reserve of LA strain and stiffness are associated with reduced functional capacity in hypertension, and LA strain reserve is independently associated with outcome. These parameters appear to be determinants of progression to overt HF in HHD; however, their contribution may differ depending on HF stage., Competing Interests: Disclosures None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs preeclamptic pregnancies., Methods: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum., Results: Recruited subjects (n = 68) were grouped according to their blood pressure as: a) normotensive pregnancy n = 15; b) PreE with normotensive postpartum (PreE-Resolved, n = 36); c) PreE with persistent postpartum HTN (PreE-HTN, n = 17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], P < .001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, P < .001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, P < .001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, P = .001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, P = .045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, P = 0.045). Exercise duration was negatively associated with gravidity (R = -0.27, P = .029) and postpartum LV mass index (R = -0.45, P < .001), resting average E/e' (R = -0.51, P < .001), BMI (R = -0.6, P < .001) and resting SBP (R = -0.51, P < .001)., Conclusions: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors., Competing Interests: Conflict of interest None reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to evaluate and compare muscle function, exercise capacity, physical activity (PA) level, CVD risk factor knowledge level, sleep quality, fatigue and quality of life between prolactinoma patients and healthy controls., Methods: Nineteen female patients with prolactinomas and 19 healthy women were included in this study. Quadriceps muscle strength (QMS) was measured using a hand dynamometer, and muscular endurance was evaluated via the squat test. The 6-minute walking test (6MWT) distance was also measured. CVD risk factor knowledge levels were evaluated with the Cardiovascular Diseases Risk Factors Knowledge Level Scale (CARRF-KL), PA levels were assessed with the International Physical Activity Questionnaire-short form (IPAQ), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), fatigue was assessed with the Multidimensional Fatigue Rating Scale (MAF), and quality of life was assessed with the Short Form-36 questionnaire (SF-36)., Results: Patients with prolactinomas had significantly lower 6MWT distances; CARRF-KL total scores; SF-36 general health and physical limitation scores; and higher IPAQ-sitting scores than did healthy controls (p < 0.05). Moreover, there were no significant differences between the groups in terms of QMS score; number of squats; severity of IPAQ score; severity, moderate, or total walking score; total PSQI score; or total MAF score (p > 0.05)., Conclusions: Exercise capacity and quality of life are adversely affected, and sedentary behavior is observed in prolactinomas. Patients with prolactinomas have less knowledge about CVD risk factors than healthy individuals. CVD incidence and knowledge and functional capacity should be improved in patients with prolactinomas by the use of a multidisciplinary team for cardiac rehabilitation., Clinical Trial Registration: This study is part of a larger clinical trial registered on ClinicalTrials.gov prior to participant enrollment (NCT05236829)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Exercise intolerance is common in patients with heart failure with preserved ejection fraction. This review will discuss the utility of exercise hemodynamics under both diagnostic and prognostic circumstances and highlight challenges associated with making and interpreting measures taken during exercise., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The invasive cardiopulmonary exercise test (iCPET) provides a comprehensive, simultaneous evaluation of an individual's cardiovascular, respiratory, and metabolic response to exercise. The test is uniquely suited for the evaluation of exercise intolerance, as well as the deep phenotyping of disease states including pulmonary arterial hypertension and post-coronavirus disease symptomatology. Despite an expanding list of clinical and research applications, both the complexity of the test and a lack of familiarity with how the test is performed have been barriers to the widespread use of iCPET. The aim of this article is to provide practical insights into how an iCPET is performed., Competing Interests: Disclosure S.H. Visovatti has served as a consultant for United Therapeutics. Dr B.A. Maron reports receiving personal fees from Actelion Pharmaceuticals, personal fees from Tenax, personal fees from Regeneron, and grants from Deerfield Company., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiac rehabilitation (CR) significantly improves cardiovascular outcomes in patients with coronary artery disease (CAD). International guidelines vary in the minimum recommended frequency of supervised exercise from 1 to 3 sessions per week. This is the first study in the Middle East and North African regions assessing the impact of 2 versus 3 days/week of supervised exercise on peak exercise capacity in patients with CAD. Single-center retrospective cohort study involving 362 patients enrolled in the only CR center in the State of Qatar. Only high-quality data was included by strict evaluation of compliance to the exercise intervention. Fifty patients who underwent a symptom-limited exercise test before and after CR were included (31 patients on 2 days/week, 19 on 3 days/week). No significant differences were observed in baseline characteristics between groups. Exercise intervention differed significantly between groups in exercise training frequency (2 days/week: 1.97 ± 0.2 vs. 3 days/week: 2.7 ± 0.3; p  < 0.00). Peak exercise capacity as peak metabolic equivalents of task (MET) significantly increased in both groups (2 days/week: Pre 8.3 ± 2.4 vs. Post 9.4 ± 2.9, p-value 0.00; 3 days/week: Pre 7.4 ± 1.6 vs. Post 8.4 ± 2.0, p-value 0.00). No significant difference was observed between groups for change in Peak Exercise Capacity (2 days/week 1.1 ± 1.1 vs. 3 days/week 1.0 ± 0.9, p  = 0.87). When the total number of exercise sessions is equal, supervised exercise frequencies of 2 and 3 days/week may significantly and equally improve peak exercise capacity in patients with CAD.

Diastolic dysfunction plays a major role in precipitating congestive heart failure in patients with hypertrophic cardiomyopathy (HCM). In many such patients, symptoms are unmasked only during exercise because left ventricular (LV) filling pressure is normal at rest but increase with exercise. We sought to establish whether abnormal postexercise diastolic parameters are associated with reduced exercise capacity in patients with HCM. We examined 590 patients with asymptomatic/minimally symptomatic HCM (age 54 ± 14 years, 57% men, body mass index 30 ± 6 kg/m 2 , 84% on β blockers) with HCM by 2-dimensional and Doppler echocardiography at rest and after maximal treadmill exercise echocardiography (TSE). A complete echocardiogram (including LV ejection fraction, LV thickness, LV outflow tract [LVOT] gradient, degree of mitral regurgitation) was recorded. Diastolic parameters (septal and lateral [e'] velocities of the mitral annulus, peak early [E] and late [A] mitral inflow velocity, E/A ratio, E/e', right ventricular systolic pressure [RVSP], and left atrial volume index) were recorded at rest and after TSE. Exercise functional capacity was recorded and divided into <85% or >85% of age-gender predicted metabolic equivalents (AGP-METs). After maximal exercise, 32% patients had at least moderate mitral regurgitation, mean LVOT gradient was 61 ± 59 mm Hg, E/A ratio was 1.2 ± 1.0, average E/e' ratio 12.9 ± 1.0, and peak RVSP was 36 ± 15 mm Hg. Only 42% of patients achieved >85% of AGP-METs; the mean METs was 7 ± 3. On multivariable logistic regression analysis, higher body mass index (odds ratio [OR] 1.05), β-blocker use (OR 2.58), higher left atrial volume index (OR 1.02), higher peak stress LVOT gradient (LVOTG) (OR 1.06), peak stress E/e' (OR 1.04), and higher RVSP (OR 1.03) were independently associated with <85% AGP-METs achieved (all p <0.05). In conclusion, in patients with asymptomatic/minimally symptomatic HCM who underwent TSE, there is a significant and independent association between abnormal diastolic response to exercise and reduced exercise capacity in HCM. Incorporating diastolic parameters during stress echocardiography could provide incremental diagnostic utility in deciphering the exact etiology of dyspnea in such patients., Competing Interests: Declaration of competing interest Dr. Milind Desai is a consultant and has research agreements with Bristol Myers Squibb, Cytokinetics, Tenaya, Viz-AI, and Edgewise. No industry support was utilized in the conduct of this study. The remaining authors have no competing interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known. Research question Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity?, Methods: Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories., Results: 40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27 kg/m 2 ). The presence of diabetes was independently associated with a reduction in FEV1 (- 130 ml), FVC (- 220 ml), DLCO (- 1.52 ml/min/mmHg), and VA (- 340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), p < 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI., Conclusion: The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although cardiopulmonary exercise testing (CPET) parameters have known prognostic value in adults after Fontan palliation, there are limited data correlating treadmill CPET with invasive exercise hemodynamics. Furthermore, the invasive hemodynamic underpinnings of exercise limitations have not been thoroughly investigated. This is a retrospective analysis of 55 adults (age ≥18 years) with prior Fontan palliation who underwent treadmill CPET before invasive exercise hemodynamic testing using a supine cycle protocol between November 2018 and April 2023. The median age was 32.2 (IQR 24.1; 37.2) years. The peak heart rate (HR) was 139.7 ± 28.1 beats per minute and the peak oxygen consumption (VO 2 ) was 19.1 ± 5.7 ml/kg/min (47.4 ± 13.5% predicted). VO 2 /HR was directly related to exercise stroke volume index (r = 0.50, p = 0.0002), whereas no association was seen with exercise arterio-mixed venous O 2 content difference (r = 0.14, p = 0.32). Peak HR was inversely related to exercise pulmonary artery (PA) pressures (r = -0.61, p <0.0001) and PA wedge pressures (PAWP) (r = -0.61, p <0.0001). Moreover, %predicted VO 2 was inversely related to exercise PA pressures (r = -0.50, p <0.0001) and PAWP (r = -0.55, p <0.0001). Peak VO 2 ≤19.1 ml/kg/min had a sensitivity of 81% and a specificity of 76% (area under the curve 0.82) for predicting a ΔPAWP/ΔQs ratio >2 mmHg/L/min and/or a ΔPA/ΔQp >3 mmHg/L/min, whereas a predicted peak VO 2 ≤48% had a sensitivity of 74% and a specificity of 81% (area under the curve 0.79) for the same parameters. In summary, lower peak HR and peak VO 2 were associated with higher exercise PAWP and PA pressure. Peak VO 2 ≤48% predicted provided the optimal cutoff for predicting increased indexed exercise PAWP or PA pressures; therefore, low peak VO 2 should alert clinicians of abnormal underlying hemodynamics., Competing Interests: Declaration of competing interest Dr. Egbe is supported by National Heart, Lung, and Blood Institute grants (K23 HL141448, R01 HL158517, and R01 160761)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Chronotropic incompetence (ChI) is linked with diminished exercise capacity in heart failure with preserved ejection fraction (HFpEF). Although exercise training has shown potential for improving functional capacity, the exercise modality associated with greater functional and chronotropic response (ChR) is not well-known. Additionally, how the ChR from different exercise modalities mediates functional improvement remains to be determined. This study aimed to evaluate the effect of three different exercise programs over current guideline recommendations on peak oxygen consumption (peakVO 2 ) in patients with ChI HFpEF phenotype., Methods and Results: In this randomized clinical trial, 80 stable symptomatic patients with HFpEF and ChI (NYHA class II-III/IV) are randomized (1:1:1:1) to receive: a) a 12-week program of supervised aerobic training (AT), b) AT and low to moderate-intensity strength training, c)AT and moderate to high-intensity strength training, or d) guideline-based physical activity and exercise recommendations. The primary endpoint is 12-week changes in peakVO 2 . The secondary endpoints are 12-week changes in ChR, 12-week changes in quality of life, and how ChR changes mediate changes in peakVO 2 . A mixed-effects model for repeated measures will be used to compare endpoint changes. The mean age is 75.1 ± 7.2 years, and most patients are women (57.5 %) in New York Heart Association functional class II (68.7 %). The mean peakVO 2 , percent of predicted peakVO 2 , and ChR are 11.8 ± 2.6 mL/kg/min, 67.2 ± 14.7 %, and 0.39 ± 0.16, respectively. No significant baseline clinical differences between arms are found., Conclusions: Training-HR will evaluate the effects of different exercise-based therapies on peakVO 2 , ChR, and quality of life in patients with ChI HFpEF phenotype., Clinical Trial Registration: ClinicalTrials.gov (NCT05649787)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: There are few studies that have used inspiratory muscle training (IMT) as an intervention for patients with isolated idiopathic pulmonary fibrosis (IPF). This study aimed to investigate and interpret the effects of home-based telerehabilitation-assisted IMT in patients with IPF., Methods: Twenty-eight participants with IPF took part in the study. Lung function tests, functional exercise capacity by 6-min walk distance (6MWD), dyspnoea perception by modified medical research council dyspnoea scale (mMRC), and inspiratory muscle strength by maximal inspiratory pressure (MIP) were assessed. IMT was performed twice a day, 7 days/week, for 8 weeks. The intervention group (n = 14) performed IMT at 50% of their baseline MIP while the control group (n = 14) performed IMT without applied resistance. Loading intensity was progressed by keeping the load at 4-6 on a modified Borg scale for the highest tolerable perceived respiratory effort for each patient., Results: Dyspnoea based on mMRC score (p < 0.001, η 2 effect size = 0.48) significantly decreased within the intervention group compared with the control group. There were significant increases in the intervention group compared to the control group based on 6MWD (p < 0.001, η 2 effect size = 0.43), MIP (p = 0.006, η 2 effect size = 0.25) and MIP % predicted (p = 0.008, η 2 effect size = 0.25)., Conclusion: The findings of this study suggest that an 8-week home-based telerehabilitation-assisted IMT intervention produced improvements in inspiratory muscle strength, leading to improvements in functional exercise capacity and dyspnoea., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Introduction: Chronic Chagas cardiomyopathy (CCC), the most severe clinical condition of Chagas disease, often leads to a reduction in functional capacity and the appearance of symptoms such as fatigue and dyspnea on exertion. However, its determinant factors remain unclear. We aimed to evaluate the peak oxygen consumption (VO 2peak ) in patients with CCC and identify its determining factors., Methods: An observational study with 97 CCC patients was conducted. Patients underwent clinical examination, cardiopulmonary exercise test (CPET), and echocardiography as part of the standard clinical evaluation. Multivariate linear regression was used to identify independent clinical and echocardiographic predictors of VO 2peak and percentage of predicted VO 2 ., Results: Mean age of study patients was 55.9 ± 13.4 years, median left ventricle ejection fraction (LVEF) was 40 (26-61.5) % and median VO 2peak was 16.1 (12.1-20.8) ml/Kg/min. 36 patients presented preserved LVEF and 61 presented reduced LVEF. There were significant differences in almost all CPET variables (p < 0.05) between these two groups. VO 2peak was associated with age, male sex, NYHA functional class, LVEF, left atrium diameter, LV diastolic diameter, E wave, LV mass index, and pulmonary artery systolic pressure (PASP). Age, male sex, LVEF, and E wave remained independently associated with VO 2peak in the multivariate analysis (R 2  = 0.69), furthermore, only LVEF and E wave were associated with the predicted VO 2 percentage (R 2  = 0.53)., Conclusion: In patients with CCC, disease severity, male sex, LV systolic and diastolic function influence the functional capacity., Competing Interests: Declaration of competing interest All authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Cardiopulmonary exercise testing (CPET) has an important prognostic value in adults with different congenital heart defects (CHDs) and is a useful tool for risk stratification and clinical decision-making. In this retrospective study, we studied the prognostic value of CPET in paediatric patients with CHD., Methods: 411 CPET performed by paediatric patients with different CHDs were evaluated in this retrospective study. Medical records were reviewed to determine the presence of cardiac events. Participants were classified using the 2018 AHA/ACC guideline for the management of adults with CHD that combines anatomical complexity and current physiological stage., Results: 411 patients with a median age at test of 12 years, 51 patients with simple CHD, 170 patients with moderate complexity CHD and 190 with high complexity CHD underwent CPET. Overall, CPET parameters were lower than the reference values (%predicted VO 2peak =75% and %predicted oxygen uptake efficiency slope (OUES)=79%), showing worst exercise capacity in the most complex types of CHD (Group III: %predicted VO 2peak =72% and %predicted OUES=75%). Seventy-one patients presented with cardiac events at a median time from CPET to first event of 28 months. Patients with cardiac events had lower exercise performance as compared with patients without cardiac events as determined by the submaximal variables (%predicted OUES: HR=2.6 (1.5-4.4), p<0.001 and VE/VCO 2 : HR=2.2 (1.4-3.5), p=0.001)., Conclusion: Reduced exercise capacity at young age is related to a higher probability of future cardiovascular events in paediatric patients with CHD. Submaximal exercise variables can be used instead when maximal exercise cannot be achieved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sedentary lifestyle is reported to be associated with diminished exercise capacity, resulting in increased cardiovascular risk in adults with congenital heart disease (CHD). This cross-sectional study examined the association between objectively measured physical activity (PA) and exercise capacity in children and adolescents with CHD. Therefore, 107 patients (aged 13.0 ± 2.7 years, 41 girls) with various CHD performed a cardiopulmonary exercise test to quantify their peak oxygen uptake (peakV'O2). Moderate to vigorous PA (MVPA) and daily step count were assessed using Garmin vivofit jr. (Garmin, Germany) for 7 consecutive days. For association between PA and submaximal exercise capacity, Spearman correlation was performed. Patients with CHD showed almost normal values compared with the reference (79.5 ± 17.2% [31.6 to 138.1] %peakV'O2 predicted), with roughly normal ventilatory anerobic thresholds (50.6 ± 14.0% [20.3 to 97.9] % oxygen uptake at ventilatory anaerobic threshold [VATV'O2]). Step counts are below the recommendations (9,304 ± 3,792 steps/day [1,701 to 20,976]), whereas MVPA data are above the recommendations for children with ≥60 min/day (83.6 ± 34.6 min/day [10.1 to 190.9]). The Spearman rho showed significant positive correlations to VATV'O2 (r = 0.353, p <0.001) and %VATV'O2 (r = 0.307, p = 0.001), with similar results regarding MVPA (VATV'O2: r = 0.300, p = 0.002 and %VATV'O2: r = 0.270, p = 0.005). In conclusion, submaximal exercise capacity and PA correlate positively, making both assessments relevant in a clinical setting: PA in the context of cardiovascular prevention and peakV'O2 as the strongest predictor for morbidity and mortality., Competing Interests: Declaration of competing interest JH and LW received an unrestricted grant from Stiftung KinderHerz Deutschland gGmbH. The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR., Objectives: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial., Methods: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m 2 ) [95% CI: 26.1-29.5 kg/m 2 )]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31 phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments., Results: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009)., Conclusions: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939)., Competing Interests: Funding Support and Author Disclosures The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the Department of Health and Social Care. This independent research has been jointly funded by the Wellcome Trust (grant number: 221690/Z/20/Z) and Diabetes UK (grant number:18/0005870) and has been performed at the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC) (NIHR203331). Funding for open access charge is from Wellcome Trust (grant number: 221690/Z/20/Z). Dr Chowdhary has received grants from the British Heart Foundation (grant number: FS/CRTF/20/24003). Dr Valkovič has received grants from the Sir Henry Dale Fellowship supported jointly by the Wellcome Trust and the Royal Society (#221805/Z/20/Z), and Slovak Grant Agencies VEGA (#2/0004/23) and APVV (#21-0299). Dr Levelt acknowledges support from the Wellcome Trust Clinical Career Development Fellowship (grant number: 221690/Z/20/Z), Diabetes UK (grant number: UK 18/0005908) and the NIHR Leeds Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The study aims to investigate exercise-limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test., Methods and Results: A symptom-limited ramp bicycle exercise test was performed in the semi-supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty-six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex-matched 29 controls. At rest, compared with controls, E/E' ratio (6.26 ± 2.3 vs. 14 ± 2.5, P < 0.001) and systolic pulmonary artery pressures (SPAP) (22.6 ± 3.4 vs. 34 ± 6.2 mmHg, P = 0.023) were increased. Along with the stages of exercise (unloaded; anaerobic threshold; peak), diastolic function worsened (E/e' 8.9 ± 2.6 vs. 13.8 ± 3.6 P = 0.011; 9.4 ± 2.3 vs. 18.6 ± 3.3 P = 0.001; 8.7 ± 1.9 vs. 21.5 ± 4, P < 0.001), SPAP increased (23 ± 2.7 vs. 33 ± 4.4, P = 0.013; 26 ± 3.2 vs. 40 ± 2.9, P < 0.001; 26 ± 3.5 vs. 45 ± 7 mmHg, P < 0.001), and oxygen consumption (6.6 ± 1.7 vs. 6.8 ± 1.6, P = 0.86; 18.1 ± 2.2 vs. 14.6 ± 1.5, P = 0.008; 20.3 ± 3 vs. 15.1 ± 2.1 mL/kg/min, P = 0.01) was reduced. Oxygen pulse was blunted (6.3 ± 1.8 vs. 6.2 ± 1.9, P = 0.79; 10 ± 2.1 vs. 8.8 ± 1.6, P = 0.063; 12.2 ± 2 vs. 8.2 ± 2.3 mL/beat, P = 0.002) due to an insufficient increase in both stroke volume (92.3 ± 17 vs. 77.3 ± 14.5 P = 0.021; 101 ± 19.1 vs. 87.3 ± 15.7 P = 0.06; 96.5 ± 12.2 vs. 83.6 ± 16.1 mL, P = 0.034) and oxygen extraction (0.07 ± 0.03 vs. 0.07 ± 0.02, P = 0.47; 0.13 ± 0.02 vs. 0.10 ± 0.03, P = 0.013; 0.13 ± 0.03 vs. 0.11 ± 0.03, P = 0.03). Diastolic dysfunction, elevated SPAP, and the presence of atrial fibrillation were associated with reduced exercise capacity., Conclusions: Both central and peripheral cardiovascular limitations are involved in exercise intolerance in HCM. Diastolic dysfunction seems to be the main driver for this limitation., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Frailty is an obstacle to performing cardiopulmonary exercise test (CPET) in patients with chronic heart failure (CHF). We evaluated the usefulness of oxygen uptake efficiency slope (OUES) using a 6 min walk test (6MWT) with portable gas analysis compared with CPET-derived parameters in patients with CHF., Methods and Results: Patients with CHF who underwent both the 6MWT with portable gas analysis and CPET between December 2016 and May 2020 were retrospectively investigated. The 6MWT-derived and echocardiographic parameters were compared with the OUES and peak oxygen consumption (VO 2 ) from the CPET. Forty patients were analysed; 50% were male with a mean age of 55.45 ± 14.70 years. Twenty-six patients (65%) had New York Heart Association Functional Classification II or III dyspnoea. Twenty-five patients (62.5%) had heart failure (HF) with preserved ejection fraction (EF) (left ventricular EF > 50%), and nine patients (22.5%) had HF with reduced EF (EF < 40%). During the 6MWT, the peak VO 2 was 14.97 ± 3.80 mL/kg/min, which was only 74% of the peak VO 2 in the CPET, 20.18 ± 5.64 mL/kg/min. The OUES in the 6MWT was lower than that in the CPET (1528.87 ± 579.01 in the 6MWT vs. 1638.69 ± 601.31 in the CPET). The 6 min walk distance (6MWD) and OUES in the 6MWT were positively correlated with the OUES in the CPET (6MWD, r = 0.434, P = 0.005; OUES, r = 0.729, P < 0.001). The OUES in the 6MWT showed the strongest correlation with the OUES in the CPET. When we divided patients into two groups according to peak VO 2 in the CPET, the correlation between OUES values of the 6MWT and that of the CPET was consistently confirmed (peak VO 2  ≥ 20 mL/kg/min group, r = 0.661, P = 0.001; peak VO 2  < 20 mL/kg/min group, r = 0.526, P = 0.021). In addition, the 6MWD, OUES, and peak VO 2 in the 6MWT were associated with peak VO 2 in the CPET (6MWD, r = 0.627, P < 0.001; OUES, r = 0.452, P = 0.003; and peak VO 2 , r = 0.492, P = 0.001)., Conclusions: In frail patients with CHF who have difficulty performing maximal exercises, the OUES through the 6MWT may be applied instead of the OUES and peak VO 2 from the CPET., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation., Methods: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO 2 ) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO 2 slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO 2 , and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity., Results: Peak VO 2 during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P =0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO 2 /dL blood; P <0.001). During single leg knee extension, there was no difference in peak leg VO 2 ( P =0.306), but the peripherally limited group had greater blood flow/VO 2 ratio ( P =0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO 2 /dL blood; P =0.013), and lower muscle oxygen diffusive conductance ( P =0.021). A difference in magnetic resonance spectroscopy-derived phosphocreatine recovery time was not detected ( P =0.199)., Conclusions: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O 2 ratio and poor muscle diffusive capacity., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844., Competing Interests: None.

Introduction: Cardiopulmonary exercise testing (CPET) is the gold standard for measuring exercise capacity, however, it is resource intensive and has limited availability. This study aimed to determine: 1) the association between the 6-min walk test (6MWT) and the 30-s sit-to-stand test (30STS) with CPET peak oxygen uptake (VO 2peak ) and anaerobic threshold (AT) and 2) 6MWT and 30STS cut points associated with a higher risk of postoperative complications., Methods: A cross-sectional study, retrospectively analyzing data collected from a tertiary cancer center over a 23-month period. Measures included CPET VO 2peak and AT, 6MWT and 30STS test. Correlations were used to characterize relationships between variables. Receiver operating characteristic curve analyses determined 6MWT and 30STS cut points that aligned with CPET variable cut points., Results: Note that, 156 participants were included. The 6MWT and 30STS displayed moderate correlations with VO 2peak , rho = 0.65, p = 0.01 and rho = 0.52, p < 0.005 respectively. Fair correlations were observed between AT and 6MWT (rho = 0.36, p = 0.01) and 30STS (rho = 0.41, p < 0.005). The optimal cut points to identify VO 2peak  < 15 mL/kg/min were 493.5 m on the 6MWT and 12.5 stands on the 30STS test and for AT < 11 mL/kg/min were 506.5 m on the 6MWT and 12.5 stands on the 30STS test., Conclusion: Both the 6MWT and 30STS test could be used as alternative tools for measuring exercise capacity preoperatively in the cancer setting where CPET is not available. A range of 6MWT and 30STS cut points, according to sensitivity and specificity levels, may be used to evaluate risk of postoperative outcomes., (© 2024 The Authors. Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Objective: To investigate the effects of computerized wobble board exercise training (CWBET) and core stabilization exercise training (CSET) on balance performance, and exercise capacity in patients with heart failure (HF)., Desing: Single-blind randomized controlled prospective study., Setting: Cardiology department of a local university hospital., Participants: Fifty-one patients with HF with reduced ejection fraction, whose clinical status and medication had been stable for the previous 3 months, were included (N=51). Nine patients could not complete the follow-up period due to personal reasons. No patient experienced any adverse events during exercise training., Interventions: Patients were randomized to CWBET, CSET, and control group. CWBET and CSET groups participated in their own exercise programs, 3 days a week for 8 weeks. The control group received no exercise program., Main Outcome Measures: All patients were evaluated at baseline and after 8 weeks. Postural stability, static and functional balance, and exercise capacity were evaluated with the Sensamove Balance Test Pro with Miniboard, the one-leg stance test (OLS), the Berg Balance Scale (BBS), and the six-minute walk distance (6MWD), respectively. Core stabilization and health-related quality of life (HRQOL) were assessed with OCTOcore app, and Minnesota Living with Heart Failure Questionnaire, respectively., Results: A mixed model repeated-measures ANOVA revealed significant group × time interaction effect for static postural stability performance (P<.001, η p 2 =0.472), vertical (P<.001, η p 2 =0.513), horizontal performance (P<.001, η p 2 =0.467), OLS (P<.001, η p 2 =0.474), BBS (P<.001, η p 2 =0.440) scores, 6MWD (P<.001, η p 2 =0.706), and HRQOL. Post hoc analysis revealed CWBET and CSET groups had similar improvements balance performance, exercise capacity, and HRQOL and both groups significantly improved compared with control group (P<.001). Core stabilization was significantly improved only in CSET group after 8 weeks., Conclusion: CWBET and CSET programs were equally effective and safe for improving balance performance and exercise capacity in patients with HF., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Obesity and exercise intolerance greatly reduce the life quality of older people. Prolyl hydroxylase domain-containing protein 2 (PHD2) is an important enzyme in modulating hypoxia-inducible factor-alpha (HIF) protein. Using vascular endothelial cell-specific PHD2 gene knockout (PHD2 ECKO) mice, we investigated the role of endothelial PHD2 in aging-related obesity and exercise capacity. Briefly, PHD2 ECKO mice were obtained by crossing PHD2-floxed mice with VE-Cadherin (Cdh5)-Cre transgenic mice. The effect of PHD2 ECKO on obesity and exercise capacity in PHD2 ECKO mice and control PHD2 f/f mice were determined in young mice (6 to 7 months) and aged mice (16-18 months). We found that aged PHD2 ECKO mice, but not young mice, exhibited a lean phenotype, characterized by lower fat mass, and its ratio to lean weight, body weight, or tibial length, while their food uptake was not reduced compared with controls. Moreover, as compared with aged control mice, aged PHD2 ECKO mice exhibited increased oxygen consumption at rest and during exercise, and the maximum rate of oxygen consumption (VO 2 max) during exercise. Furthermore, as compared with corresponding control mice, both young and aged PHD2 ECKO mice demonstrated improved glucose tolerance and lower insulin resistance. Together, these data demonstrate that inhibition of vascular endothelial PHD2 signaling significantly attenuates aging-related obesity, exercise intolerance, and glucose intolerance., (© 2024. The Author(s).)

Assessing the functional capacity and exercise tolerance is an important and widely used research tool in patients with heart failure. It is used not only in cardiac rehabilitation and physical therapy, but also for inclusion criteria and outcome measures in studies of drug interventions. This document outlines the scope, guidelines for the implementation and interpretation, and limitations of the methods for assessing the functional capacity and exercise tolerance in clinical trials in patients with heart failure.

Abstract: Arroum, T, Hish, GA, Burghardt, KJ, Ghamloush, M, Bazzi, B, Mrech, A, Morse, PT, Britton, SL, Koch, LG, McCully, JD, Hüttemann, M, and Malek, MH. Mitochondria transplantation: Rescuing innate muscle bioenergetic impairment in a model of aging and exercise intolerance. J Strength Cond Res 38(7): 1189-1199, 2024-Mitochondria, through oxidative phosphorylation, are crucial for energy production. Disease, genetic impairment, or deconditioning can harm muscle mitochondria, affecting energy production. Endurance training enhances mitochondrial function but assumes mobility. Individuals with limited mobility lack effective treatments for mitochondrial dysfunction because of disease or aging. Mitochondrial transplantation replaces native mitochondria that have been damaged with viable, respiration-competent mitochondria. Here, we used a rodent model selectively bred for low-capacity running (LCR), which exhibits innate mitochondrial dysfunction in the hind limb muscles. Hence, the purpose of this study was to use a distinct breed of rats (i.e., LCR) that display hereditary skeletal muscle mitochondrial dysfunction to evaluate the consequences of mitochondrial transplantation. We hypothesized that the transplantation of mitochondria would effectively alleviate mitochondrial dysfunction in the hind limb muscles of rats when compared with placebo injections. In addition, we hypothesized that rats receiving the mitochondrial transplantation would experience an improvement in their functional capacity, as evaluated through incremental treadmill testing. Twelve aged LCR male rats (18 months old) were randomized into 2 groups (placebo or mitochondrial transplantation). One LCR rat of the same age and sex was used as the donor to isolate mitochondria from the hindlimb muscles. Isolated mitochondria were injected into both hindlimb muscles (quadriceps femoris, tibialis anterior (TA), and gastrocnemius complex) of a subset LCR (n = 6; LCR-M) rats. The remaining LCR (n = 5; LCR-P) subset received a placebo injection containing only the vehicle without the isolated mitochondria. Four weeks after mitochondrial transplantation, rodents were euthanized and hindlimb muscles harvested. The results indicated a significant (p < 0.05) increase in mitochondrial markers for glycolytic (plantaris and TA) and mixed (quadricep femoris) muscles, but not oxidative muscle (soleus). Moreover, we found significant (p < 0.05) epigenetic changes (i.e., hypomethylation) at the global and site-specific levels for a key mitochondrial regulator (transcription factor A mitochondrial) between the placebo and mitochondrial transplantation groups. To our knowledge, this is the first study to examine the efficacy of mitochondrial transplantation in a rodent model of aging with congenital skeletal muscle dysfunction., (Copyright © 2024 National Strength and Conditioning Association.)