Recalibrated FRIEND equation for peak oxygen pulse is accurate in endurance athletes: the NOODLE study.

Peak oxygen pulse (O2Ppeak) is an important index of cardiorespiratory fitness (CRF). The FRIEND database is a global source of reference values for CRF. However, no reference equation is tailored for endurance athletes (EA) to predict O2Ppeak. Here, we adjusted the well-established FRIEND equation for O2Ppeak to the characteristics of the EA population. 32 (34.0%) female EA and 62 (66.0%) male well-trained EA underwent maximal cardiopulmonary exercise test on a treadmill. V̇O2max was 4.5 ± 0.5 L min-1 in males and 3.1 ± 0.4 L min-1 in females. O2Ppeak was 23.6 ± 2.8 mL beat-1 and 16.4 ± 2.0 mL beat-1 for males and females, respectively. Firstly, we externally validated the original FRIEND equation. Secondly, using multiple linear regression, we adjusted the FRIEND equation for O2Ppeak to the population of EA. The original FRIEND equation underestimated O2Ppeak for 2.9 ± 2.9 mL beat-1 (P < .001) in males and 2.2 ± 2.1 mL beat-1 (P < .001) in females. The updated equation was 1.36 + 1.07 (23.2 · 0.09 · age - 6.6 [if female]). The new equation explained 62% of the variance and significantly predicted O2Ppeak (R2 = 0.62, ß = 0.78, P < .001). The error of the EA-adjusted model was 0.1 ± 2.9 mL beat-1 (P = .82) and 0.2 ± 2.1 mL beat-1 (P = .65) for males and females respectively. Recalibration of the original FRIEND equation significantly enhances its accuracy among EA. The error of the EA-adjusted model was negligible. A new recalibrated equation should be used to predict O2Ppeak in the population of EA.

Effects of sildenafil on gas exchange, ventilatory, and sensory responses to exercise in subjects with mild-to-moderate COPD: a randomized cross-over trial.

Excess exercise ventilation (high ventilation (V̇E)/carbon dioxide output (V̇CO2)) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇E/V̇CO2 and dyspnea in patients with early COPD. We aimed to assess whether a clinically more practical option - oral sildenafil - would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV1= 69.4 ± 13.5% predicted) showed higher ventilatory demands (V̇E/V̇CO2), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV1= 98.3 ±11.6% predicted). Contrary to our expectations, however, sildenafil (50mg; N= 15) did not change exertional V̇E/V̇CO2, dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (P>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation. Clinical trial registry: https://ensaiosclinicos.gov.br/rg/RBR-4qhkf4 Web of Science Researcher ID: O-7665-2019.

Changes in Cerebral Oxygenation in the Prefrontal Cortex During Cardiopulmonary Exercise Testing in Patients After Cardiovascular Surgery.

Oxygenated haemoglobin (O2Hb) and total haemoglobin (THb) concentrations rise with increasing exercise load during the cardiopulmonary exercise test (CPX); however, this elevated response is impaired in patients with chronic heart failure. Furthermore, the changes occurring in patients during the acute phase of cardiac surgery are unknown. This study aimed to measure cerebral oxygenation in the prefrontal cortex (PFC) during CPX in patients during the acute post-operative phase following cardiovascular surgery. Fourteen patients in the acute phase of post-cardiovascular surgery period were enrolled. CPX was administered between the post-operative period and discharge. The protocol employed the ramp method (10 W/min) after 3-min rest and 3-min warm-up periods. Levels of O2Hb, deoxygenated haemoglobin (HHb), THb, and the regional cerebral oxygen saturation (rSO2) in the PFC were measured from the resting state through the end of CPX using near-infrared spectroscopy. The mean values of O2Hb, HHb, and THb levels and rSO2 were compared at rest, warm-up, anaerobic threshold, and peak points. At the peak, O2Hb and rSO2 declined significantly, and HHb rose significantly compared to the respective values at rest; no significant changes were observed in THb. These findings suggest that the oxygen supply to the PFC is reduced in patients with reduced cardiac function following cardiovascular surgery.

Changes in hematopoietic stem cell numbers following acute exercise in non-athlete marathon runners.

PURPOSE: Hematopoietic stem cell (HSC) transplant is one of the curative methods for some patients with hematological malignancies. Granulocyte colony-stimulating factor (G-CSF) is the most common drug used to mobilize CD34+ cells, generally found in small numbers. Recent evidence showed that exercise causes transient mobilization in HSC. However, the type and intensity of exercise have not been fully revealed. We aimed to detect a significant increase in stem cell levels following 60 â€‹min of running at a personalized running pace. MATERIALS/METHODS: Eighteen runners, 48.2 â€‹± â€‹1.9 years with peak oxygen consumption of 46.2 â€‹± â€‹1.4 â€‹ml/kg/min, were enrolled in the study. The cardiopulmonary exercise test was performed to determine the individual running pace, and the participants ran 60-min on a treadmill at an intensity close to their ventilatory threshold (VT). The blood sampling for HSC count was performed before, immediately after, at the 1st, 4th and 24th hour after the 60-min running. RESULTS: The CD34+ HSCs were 13.9 â€‹± â€‹2.3 â€‹cells/µl before and significantly increased immediately after to 19.5 â€‹± â€‹3.6 â€‹cells/µl (p â€‹< â€‹0.05). The consecutive HSC counts were 15.3 â€‹± â€‹2.2, 19.5 â€‹± â€‹4.8 and 15.1 â€‹± â€‹3.4 â€‹cells/µl at the 1st, 4th, and 24th hour, respectively. CONCLUSION: The individual data showed that some runners had higher HSC levels than the transplantation limit before and after the 60-min running trail, which was maintained for 24 â€‹h. Pre-running high CD34+ HSCs may reflect an adaptive response to regular exercise, with a 60-min run near the VT further elevating HSCs. Individualized exercise may be a valuable tool to mobilize the CD34+ HSCs in peripheral blood for donors.

Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established. METHODS AND RESULTS: This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively). In the ATTR-CA group, the median age was 75.5 years (interquartile range [IQR] 71.3-78.8 years), 90.6% were male, and the median left ventricular (LV) ejection fraction was 53.5% (IQR 41.4-65.6%). Cardiopulmonary exercise tests revealed a median peak oxygen consumption and anaerobic threshold of 15.9 (IQR 11.6-17.4) and 10.6 (IQR 8.5-12.0] mL/min/kg, respectively, and ventilatory efficiency (minute ventilation/carbon dioxide production [V̇E/V̇CO2] slope) of 35.5 (IQR 32.0-42.5). Among exercise variables, V̇E/V̇CO2slope has the greatest prognostic value. Univariate analysis revealed a significant correlation between V̇E/V̇CO2slope and age, LV global longitudinal strain, tricuspid annular plain systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and mixed venous oxygen saturation. In multivariate analyses, the TAPSE/PASP ratio was an independent predictor of V̇E/V̇CO2slope (95% confidence interval -44.5, -10.8; P=0.0067). In non-amyloidosis HFpEF/HFmrEF patients, the TAPSE/PASP ratio was not independently correlated with V̇E/V̇CO2slope. CONCLUSIONS: Right ventricular-pulmonary artery coupling estimated by the TAPSE/PASP ratio determines exercise capacity in ATTR-CA patients. This highlights the importance of early therapeutic intervention against underappreciated right ventricular dysfunction associated with ATTR-CA.

Validity of estimated aortic pulse wave velocity measured during the 6-min walk test to predict anaerobic fitness before major non-cardiac surgery.

BACKGROUND: This study aimed to assess the efficacy of estimated preoperative aortic pulse wave velocity (AoPWV) to discriminate between low and high 6 min walk test (6MWT) distance in patients awaiting major non-cardiac surgery. METHODS: Prospective observational study in 133 patients undergoing non cardiac surgery. AoPWV and the distance walked during a 6MWT were assessed. Receiver operating characteristic (ROC) curve analysis was used to determine two different AoPWV cut-points for predicting a distance of 427 m in the 6MWT. We also calculated lower and upper AoPWV cut-points (probability ≥ 0.75) for predicting a distance of < 427 m, ≥427 m, and also 563 m in the 6MWT. RESULTS: The ROC curve analysis for the < 427 m distance revealed an area under the curve (AUC) of 0.68 (95% confidence interval 0.56-0.79) and an AUC of 0.72 (95% confidence interval 0.61-0.83) for >563 m. Patients with AoPWV > 10.97 m/s should be considered high risk, while those with <9.42 m/s can be considered low risk. CONCLUSIONS: AoPWV is a simple, non-invasive, useful clinical tool for identifying and stratifying patients awaiting major non-cardiac surgery. In situations of clinical uncertainty, additional measures should be taken to assess the risk.

Efficacy and safety of macitentan in Fontan-palliated patients: 52-week randomized, placebo-controlled RUBATO Phase 3 trial and open-label extension.

OBJECTIVES: The efficacy and safety of macitentan, an endothelin receptor antagonist, were assessed in a 52-week, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent patients (RUBATO-DB) and an open-label extension trial (RUBATO-OL). METHODS: Patients aged 12 years and older with New York Heart Association functional class II or III underwent total cavopulmonary connection more than 1 year before screening and showed no signs of Fontan failure/clinical deterioration. In RUBATO-DB, the primary efficacy end point was change in peak oxygen consumption from baseline to week 16; secondary end points were change from baseline over 52 weeks in peak oxygen consumption and change in mean count/minute of daily physical activity via accelerometer from baseline to week 16. Safety was assessed throughout both studies. RESULTS: In RUBATO-DB, 137 patients were randomized to macitentan 10 mg (n = 68) or placebo (n = 69); 92.7% completed 52-week double-blind treatment. At week 16, mean ± SD change in peak oxygen consumption was -0.16 ± 2.86 versus -0.67 ± 2.66 mL/kg/minute with macitentan versus placebo (median unbiased treatment difference estimate, 0.62 mL/kg/minute [99% repeated CI, -0.62 to 1.85]; P = .19). No treatment effect was observed in either of the secondary end points. During RUBATO-DB, most common adverse events with macitentan were headache, nasopharyngitis, and pyrexia. Across RUBATO-DB and RUBATO-OL, most common adverse events were COVID-19, headache, and fatigue. RUBATO-OL was prematurely discontinued because RUBATO-DB did not meet its primary or secondary end point. CONCLUSIONS: The primary end point of RUBATO-DB was not met; macitentan did not improve exercise capacity versus placebo in patients with Fontan palliation. Macitentan was generally well tolerated over long-term treatment.

Differences in Exercise Capacity, Ventilatory Efficiency, and Gas Exchange between Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension Residing at High Altitude.

Background: Cardiopulmonary exercise testing (CPET) assesses exercise capacity and causes of exercise limitation in patients with pulmonary hypertension (PH). At altitude, changes occur in the ventilatory pattern and a decrease in arterial oxygen pressure in healthy; these changes are increased in patients with cardiopulmonary disease. Our objective was to compare the response to exercise and gas exchange between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) residing at the altitude of Bogotá (2640 m). Methods: All patients performed an incremental CPET with measurement of oxygen consumption ( VO 2 ), dead space (VD/VT), ventilatory equivalents (VE/ VCO 2 ), and alveolar-arterial oxygen gradient ( PA-aO 2 ). X 2 test and one-way analysis of variance were used for comparisons between PAH and CTEPH. Results: We included 53 patients, 29 with PAH, 24 with CTEPH, and 102 controls as a reference of the normal response to exercise at altitude. CTEPH patients had a higher New York Health Association (NYHA) functional class than PAH (p = 0.037). There were no differences between patients with PAH and CTEPH in hemodynamics and VO 2 % of predicted (67.8 ± 18.7 vs. 66.0 ± 19.8, p < 0.05), but those with CTEPH had higher dyspnea, VD/VT (0.36 ± 0.09 vs. 0.23 ± 0.9, p < 0.001), VE/ VCO 2 (45.8 ± 7.1 vs. 39.3 ± 5.6, p < 0.001), and PA-aO 2 (19.9 ± 7.6 vs. 13.5 ± 7.6, p < 0.001) than PAH patients. Conclusions: At altitude, patients with PH present severe alterations in gas exchange during exercise. There were no differences in exercise capacity between PAH and CTEPH, but patients with CTEPH had more dyspnea and greater alterations in gas exchange during exercise. CPET made it possible to identify alterations related to the pathophysiology of CTEPH that could explain the functional class and dyspnea in these patients.

Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations.

BACKGROUND: Post-exertional malaise (PEM), the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), represents a constellation of abnormal responses to physical, cognitive, and/or emotional exertion including profound fatigue, cognitive dysfunction, and exertion intolerance, among numerous other maladies. Two sequential cardiopulmonary exercise tests (2-d CPET) provide objective evidence of abnormal responses to exertion in ME/CFS but validated only in studies with small sample sizes. Further, translation of results to impairment status and approaches to symptom reduction are lacking. METHODS: Participants with ME/CFS (Canadian Criteria; n = 84) and sedentary controls (CTL; n = 71) completed two CPETs on a cycle ergometer separated by 24 h. Two-way repeated measures ANOVA compared CPET measures at rest, ventilatory/anaerobic threshold (VAT), and peak effort between phenotypes and CPETs. Intraclass correlations described stability of CPET measures across tests, and relevant objective CPET data indicated impairment status. A subset of case-control pairs (n = 55) matched for aerobic capacity, age, and sex, were also analyzed. RESULTS: Unlike CTL, ME/CFS failed to reproduce CPET-1 measures during CPET-2 with significant declines at peak exertion in work, exercise time, V ˙ e, V ˙ O2, V ˙ CO2, V ˙ T, HR, O2pulse, DBP, and RPP. Likewise, CPET-2 declines were observed at VAT for V ˙ e/ V ˙ CO2, PetCO2, O2pulse, work, V ˙ O2 and SBP. Perception of effort (RPE) exceeded maximum effort criteria for ME/CFS and CTL on both CPETs. Results were similar in matched pairs. Intraclass correlations revealed greater stability in CPET variables across test days in CTL compared to ME/CFS owing to CPET-2 declines in ME/CFS. Lastly, CPET-2 data signaled more severe impairment status for ME/CFS compared to CPET-1. CONCLUSIONS: Presently, this is the largest 2-d CPET study of ME/CFS to substantiate impaired recovery in ME/CFS following an exertional stressor. Abnormal post-exertional CPET responses persisted compared to CTL matched for aerobic capacity, indicating that fitness level does not predispose to exertion intolerance in ME/CFS. Moreover, contributions to exertion intolerance in ME/CFS by disrupted cardiac, pulmonary, and metabolic factors implicates autonomic nervous system dysregulation of blood flow and oxygen delivery for energy metabolism. The observable declines in post-exertional energy metabolism translate notably to a worsening of impairment status. Treatment considerations to address tangible reductions in physiological function are proffered. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, retrospectively registered, ID# NCT04026425, date of registration: 2019-07-17.

A standardized approach to evaluate effectiveness of aerobic exercise training interventions in cardiovascular disease at the individual level.

BACKGROUND: Reliable change indices can determine pre-post intervention changes at an individual level that are greater than chance or practice effect. We applied previously developed minimal meaningful change (MMCRCI) scores for oxygen uptake (V̇O2) values associated with estimated lactate threshold (θLT), respiratory compensation point (RCP), and peak oxygen uptake (V̇O2peak) to evaluate the effectiveness of exercise training in cardiovascular disease patients. METHODS: 303 patients (65 ± 11 yrs.; 27% female) that completed a symptom-limited cardiopulmonary exercise test (CPET) before and after 6-months of guideline-recommended exercise training were assessed to determine absolute and relative V̇O2 at θLT, RCP, and V̇O2peak. Using MMCRCI ∆V̇O2 scores of ±3.9 mL·kg-1·min-1, ±4.0 mL·kg-1·min-1, and ± 3.6 mL·kg-1·min-1 for θLT, RCP, and V̇O2peak, respectively, patients were classified as "positive" (ΔθLT, ΔRCP, and/or ΔV̇O2peak ≥ +MMCRCI), "non-" (between ±MMCRCI), or "negative" responders (≤ -MMCRCI). RESULTS: Mean RCP (n = 86) and V̇O2peak (n = 303) increased (p < 0.05) from 19.4 ± 3.6 mL·kg-1·min-1 and 18.0 ± 6.3 mL·kg-1·min-1 to 20.1 ± 3.8 mL·kg-1·min-1 and 19.2 ± 7.0 mL·kg-1·min-1 at exit, respectively, whereas θLT (n = 140) did not change (15.5 ± 3.4 mL·kg-1·min-1 versus 15.7 ± 3.8 mL·kg-1·min-1, p = 0.324). For changes in θLT, 6% were classified as "positive" responders, 90% as "non-responders", and 4% as "negative" responders. For RCP, 10% exhibited "positive" changes, 87% were "non-responders", and 2% were "negative" responders. For ΔV̇O2peak, 57 patients (19%) were classified as "positive" responders, 229 (76%) as "non-responders", and 17 (6%) as "negative" responders. CONCLUSION: Most patients that completed the exercise training program did not achieve reliable improvements greater than that of chance or practice at an individual level in θLT, RCP and V̇O2peak.

Prognostic value of cardiopulmonary exercise test in patients with acute myocardial infarction after percutaneous coronary intervention.

To determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1-2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer-Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO2), carbon dioxide ventilation equivalent slope (VE/VCO2slop), and peak end-tidal carbon dioxide partial pressure (PETCO2) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI (P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO2, VE/VCO2slop, and PETCO2. The risk of adverse events was significantly reduced when the peakVO2 was ≥ 20 mL/kg/min and the VE/VCO2slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer-Lemeshow test showed that the three models were a good fit (P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.

Feasibility of performing the 3-minute step test with remote supervision in children and adolescents with cystic fibrosis: A comparative study.

Importance: The 3-min step test is a simple option to monitor submaximal exercise capacity, although its use via remote video monitoring has not been investigated in children with cystic fibrosis (CF). Objective: This study aimed to assess the feasibility and reproducibility of performing the 3-min step test with remote supervision. Methods: A cross-sectional study including CF patients (6-18 years) from two CF services were performed. Demographic, anthropometric, clinical, and lung function data were collected and two 3-min step tests were performed: (i) in-person supervision, and (ii) remotely supervised by video monitoring. Before and after the tests, heart rate (HR), oxygen saturation (SpO2), and the Borg score for dyspnea and lower limb fatigue were monitored. Results: Twenty-three patients (10.7 ± 3.7 years) with a mean FEV1 of 89.5% ± 23.2% were included. There were no significant differences between tests, with mean differences (95% confidence intervals) in final HR of -3.3 (-8.9, 2.4), change in HR of -1.9 (-6.1, 2.1), final SpO2 of 0.3 (-0.4, 1.0), and final dyspnea of 0.1 (-0.8, 0.9). The intraclass correlation coefficient was 0.852 (final HR), 0.762 (final SpO2), and 0.775 (final lower limb fatigue). Significant and moderate correlations were found between tests for final HR (r = 0.75), change in HR (r = 0.61), and final SpO2 (r = 0.61). The Bland-Altman analysis showed a mean difference in final SpO2 between tests of 0.3% (limit of agreement -3.0%, 3.5%). Interpretation: Physiological responses between tests were similar, indicating it was feasible to perform the 3-min step test with remote supervision in CF children.

Accuracy of the 6-Minute Walk Test for Assessing Functional Capacity in Patients With Heart Failure With Preserved Ejection Fraction and Other Chronic Cardiac Pathologies: Results of the ExIC-FEp Trial and a Meta-Analysis.

BACKGROUND: Heart diseases, particularly heart failure, significantly impact patient quality of life and mortality rates. Functional capacity assessment is vital for predicting prognosis and risk in these patients. While the cardiopulmonary exercise test is considered the gold standard, the 6-minute walk test has emerged as a more accessible alternative. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity in cardiac pathologies, including heart failure with preserved ejection fraction, are unclear. The study aimed to analyse the diagnostic accuracy of the 6-minute walk test for detecting reduced functional capacity, defined as VO2max < 14 ml/kg/min, compared with the cardiopulmonary exercise test in participants with heart failure with preserved ejection fraction using data from the "Ejercicio en Insuficiencia Cardiaca con Fracción de Eyección Preservada" (ExIC-FEp) trial; and to compare these results with previous studies investigating the screening accuracy for assessing functional capacity of the 6-minute walk test in participants with other chronic cardiac pathologies through a meta-analysis. RESULTS: The ExIC-FEp trial involved 22 participants with heart failure with preserved ejection fraction, who were not treated with beta-blockers, using the cardiopulmonary exercise test, specifically VO2max, as the reference test. The 6-minute walk test had a sensitivity of 70%, a specificity of 80%, and an area under the curve of 76% in the ExIC-FEp trial. Five studies were included in the meta-analysis showing a sensitivity of 79%, a specificity of 78%, and an area under the curve of 85%. CONCLUSION: In conclusion, the 6-minute walk test holds promise as a screening tool for assessing functional capacity in heart failure with preserved ejection fraction and chronic heart diseases, with a VO2max < 14 ml/kg/min as a reference point. It demonstrates moderate to good screening accuracy. However, the screening accuracy and optimal cut-off points of the 6-minute walk test for detecting severely reduced functional capacity, regardless of aetiology, are unclear. TRIAL REGISTRATION: NCT05726474. Registered 16 February 2023, https://clinicaltrials.gov/study/NCT05726474 .

Pulmonary gas exchange and ventilatory efficiency during exercise in health and diseases.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is nowadays used to study the exercise response in healthy subjects and in disease. Ventilatory efficiency is one of the main determinants in exercise tolerance, and its main variables are a useful tool to guide pathophysiologists toward specific diagnostic pathways, providing prognostic information and improving disease management, treatment, and outcomes. AREAS COVERED: This review will be based on today's available scientific evidence, describing the main physiological determinants of ventilatory efficiency at rest and during exercise, and focusing also on how CPET variables are modified in specific diseases, leading to the possibility of early diagnosis and management. EXPERT OPINION: Growing knowledge on CPET interpretation and a wider use of this clinical tool is expected in order to offer more precise diagnostic and prognostic information to patients and clinicians, helping in the management of therapeutic decisions. Future research could be able to identify new and more simple markers of ventilatory efficiency, and to individuate new interventions for the improvement of symptoms, such as exertional dyspnea.

Upper-Body Muscular Endurance and Its Association with Aerobic Capacity in University Students of Physical Culture, Sport, and Recreation / Fuerza resistencia de miembros superiores y su asociación con la capacidad aeróbica en universitarios de cultura física, deporte y recreación / Resistência Muscular do Corpo Superior e sua Associação com Capacidade Aeróbica em Estudantes Universitários de Cultura Física, Esporte e Recreação

Abstract Introduction: Upper-body muscular endurance (UBME) and aerobic capacity (AC) are essential components of physical fitness. Low levels of these components are related to cardiovascular disease. Purpose: To assess the association between UBME and AC levels in college students of physical culture. Methodology: Analytical cross-sectional study carried out in 192 students (169 men, 23 women; median age 20 years). Every participant of the study signed written consent. UMBE was the dependent variable assessed by the push-up test, and AC was the main independent variable assessed using the 20 m shuttle run test. To analyze differences by sex, and academic semester, Fischer exact, Student's T, and U Mann-Whitney tests were applied. Descriptive, as well as bivariate and multivariate analysis, were realized using logistic regression models. Results: 82.29 % of participants had healthy levels of UBME. Respecting the academic semester, students had a higher probability of having healthy levels of UBME as semesters increased (OR: 1.23, 95 % CI: 1.06 to 1.44, p = 0.007). Concerning AC, 58.33 % of participants registered healthy levels. After adjusting by sex, age, socioeconomic level, and academic semester, maximum oxygen consumption (VO2max), was associated with healthy levels of UBME (OR: 1.157, CI 95 %: 1.O71 - 1.249, p=<0.001). Conclusions: Students had a higher probability of presenting healthy levels of UBME as semesters of study increased, and those with a higheVO2max were more likely to have healthy levels of UBME.

Resumen Introducción: La fuerza resistencia de miembros superiores (FRMS) y la capacidad aeróbica (CA) son componentes esenciales de la condición física. Bajos niveles de estos componentes están relacionados con la enfermedad cardiovascular. Propósito: El objetivo de este estudio fue evaluar la asociación entre los niveles de FRMS y la CA en estudiantes universitarios de cultura física. Metodología: Estudio transversal analítico realizado en 192 estudiantes (169 hombres, 23 mujeres; mediana de edad, 20 años). Cada participante firmó el consentimiento informado. FRMS fue la variable dependiente y se valoró con la prueba de flexiones de brazo, y la CA fue la variable independiente y se evaluó usando la prueba de ida y vuelta de 20 m. Para analizar las diferencias por sexo y semestre académico, fueron utilizadas las pruebas exacta de Fischer, T de Student y U de Mann-Whitney. Se realizaron análisis descriptivos, bivariados y múltiples, usando modelos de regresión logística. Resultados: El 82.29 % de los participantes registraron niveles saludables de FRMS. Respecto al semestre académico, se evidenció una probabilidad más alta de tener niveles saludables de FRMS al incrementarse los semestres de estudio (OR: 1.23, 95 % CI: 1.06 to 1.44, p = 0.007). En lo concerniente a la CA, el 58.33 % de los participantes registro niveles saludables. Después de realizar ajustes por sexo, edad, nivel socioeconómico y semestre académico, el consumo máximo de oxígeno (VO2máx), estuvo asociado con niveles saludables de FRMS (OR: 1.157, CI 95 % 1.O71 - 1.249, p=<0.001). Conclusiones: Los participantes presentaron una mayor probabilidad de tener niveles saludables de FRMS, a medida que incrementaron los semestres de estudio, y aquellos con niveles de VO2máx más alto, fueron más proclives a tener niveles saludables de FRMS.

Resumo Introdução: A resistência muscular do corpo superior (UBME) e a capacidade aeróbica (AC) são componentes essenciais da aptidão física. Baixos níveis desses componentes estão relacionados a doenças cardiovasculares. Propósito: Avaliar a associação entre os níveis de UBME e AC em estudantes universitários de cultura física. Metodologia: Estudo transversal analítico realizado com 192 estudantes (169 homens, 23 mulheres; idade média 20 anos). Todos os participantes do estudo assinaram consentimento por escrito. UBME foi a variável dependente avaliada pelo teste de flexão de braço, e AC foi a principal variável independente avaliada pelo teste de corrida de vaivém de 20 m. Para analisar diferenças por sexo e semestre acadêmico, foram aplicados testes exatos de Fischer, t de Student e U de MannWhitney. Análises descritivas, bivariadas e multivariadas foram realizadas usando modelos de regressão logística. Resultados: 82,29 % dos participantes apresentaram níveis saudáveis de UBME. Respeitando o semestre acadêmico, os estudantes tiveram uma probabilidade maior de ter níveis saudáveis de UBME conforme os semestres aumentavam (OR: 1,23, IC 95 %: 1,06 a 1,44, p = 0,007). Em relação à AC, 58,33 % dos participantes registraram níveis saudáveis. Após ajuste por sexo, idade, nível socioeconômico e semestre acadêmico, o consumo máximo de oxigênio (VO2max) foi associado a níveis saudáveis de UBME (OR: 1,157, IC 95 %: 1,071 - 1,249, p <0,001). Conclusões: Os estudantes tiveram uma probabilidade maior de apresentar níveis saudáveis de UBME conforme os semestres de estudo aumentaram, e aqueles com um VO2max mais alto tiveram maior probabilidade de ter níveis saudáveis de UBME.

Effect of Left Ventricular Diastolic Dysfunction on the Cardiopulmonary Exercise Test in Patients With Cardiovascular Disease.

Left ventricular diastolic dysfunction exists in patients with heart failure with reduced ejection fraction and causes activity restriction and a poor prognosis, but there have been few reports about exercise tolerance in patients with diastolic dysfunction, regardless of left ventricular ejection fraction (LVEF). In this study, 294 cardiovascular disease patients who performed a cardiopulmonary exercise test (CPX) with an adequate examination by echocardiography at Fukuoka University Hospital from 2011 to 2020 were investigated. Patients were divided into groups with grade I and grade II or III diastolic dysfunction according to diagnostic criteria, regardless of LVEF, by echocardiography. After adjusting for age, gender, body mass index, smoking, and LVEF by propensity score matching, we compared the results of CPX between the grade I and grade II/III groups. There were no significant differences in hemodynamic parameters, or in the respiratory exchange ratio, oxygen uptake per body weight, oxygen uptake per heart rate, or parameters of ventilatory volume. Ventilatory equivalents per oxygen uptake and per carbon dioxide output were significantly worse in the grade II/III group from the rest to peak periods during CPX. In conclusion, left ventricular diastolic dysfunction worsens ventilatory efficacy during CPX. This effect potentially contributes to a poor prognosis in left ventricular diastolic dysfunction.

Role of Gut Microbe Composition in Psychosocial Symptom Response to Exercise Training in Breast Cancer Survivors (ROME) study: protocol for a randomised controlled trial.

INTRODUCTION: Breast cancer survivors have an increased risk for chronic fatigue and altered gut microbiota composition, both with negative health and quality of life affects. Exercise modestly improves fatigue and is linked to gut microbial diversity and production of beneficial metabolites. Studies suggest that gut microbiota composition is a potential mechanism underlying fatigue response to exercise. Randomised controlled trials testing the effects of exercise on the gut microbiome are limited and there is a scarcity of findings specific to breast cancer survivors. The objective of this study is to determine if fitness-related modifications to gut microbiota occur and, if so, mediate the effects of aerobic exercise on fatigue response. METHODS AND ANALYSIS: The research is a randomised controlled trial among breast cancer survivors aged 18-74 with fatigue. The primary aim is to determine the effects of aerobic exercise training compared with an attention control on gut microbiota composition. The secondary study aims are to test if exercise training (1) affects the gut microbiota composition directly and/or indirectly through inflammation (serum cytokines), autonomic nervous system (heart rate variability) or hypothalamic-pituitary-adrenal axis mediators (hair cortisol assays), and (2) effects on fatigue are direct and/or indirect through changes in the gut microbiota composition. All participants receive a standardised controlled diet. Assessments occur at baseline, 5 weeks, 10 weeks and 15 weeks (5 weeks post intervention completion). Faecal samples collect the gut microbiome and 16S gene sequencing will identify the microbiome. Fatigue is measured by a 13-item multidimensional fatigue scale. ETHICS AND DISSEMINATION: The University of Alabama at Birmingham Institutional Review Board (IRB) approved this study on 15 May 2019, UAB IRB#30000320. A Data and Safety Monitoring Board convenes annually or more often if indicated. Findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04088708.

Muscle function, exercise capacity, physical activity level and cardiovascular disease risk factor knowledge in patients with prolactinoma.

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).

Association between psoas major muscle mass and CPET performance and long-term survival following major colorectal surgery: A retrospective cohort study.

OBJECTIVES: To evaluate whether computed tomography (CT)-derived psoas major muscle measurements could predict preoperative cardiopulmonary exercise testing (CPET) performance and long-term mortality in patients undergoing major colorectal surgery and to compare predictive performance of psoas muscle measurements using 2D approach and 3D approach. METHODS: A retrospective cohort study compliant with STROCSS standards was conducted. Consecutive patients undergoing major colorectal surgery between January 2011 and January 2017 following CPET as part of their preoperative assessment were included. Regression analyses were modelled to investigate association between the CT-derived psoas major muscle mass variables [total psoas muscle area (TPMA), total psoas muscle volume (TPMV) and psoas muscle index (PMI)] and CPET performance and mortality (1-year and 5-year). Discriminative performances of the variables were evaluated using Receiver Operating Characteristic (ROC) curve analysis. RESULTS: A total of 457 eligible patients were included. The median TPMA and TPMV were 21 â€‹cm2 (IQR: 15-27) and 274 â€‹cm3 (IQR: 201-362), respectively. The median PMI measured via 2D and 3D approaches were 7 â€‹cm2/m2 (IQR: 6-9) and 99 â€‹cm3/m2 (IQR: 76-120), respectively. The risks of 1-year and 5-year mortality were 7.4% and 27.1%, respectively. Regression analyses showed TPMA, TPMV, and PMI can predict preoperative CPET performance and long-term mortality. However, ROC curve analyses showed no significant difference in predictive performance amongst TPMA, TPMV, and PMI. CONCLUSION: Radiologically-measured psoas muscle mass variables may predict preoperative CPET performance and may be helpful with informing more objective selection of patients for preoperative CPET and prehabilitation.

Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.