Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

BACKGROUND: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. METHODS: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. RESULTS: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. CONCLUSIONS: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.

Feasibility of a Novel Augmented 6-Minute Incremental Step Test: A Simplified Cardiorespiratory Fitness Assessment Tool.

Background: The cardiopulmonary exercise test (CPET) is considered a gold standard in assessing cardiorespiratory fitness (CRF) but has limited accessibility due to competency requirements and cost. Incorporating portable sensor devices into a simple bedside test of CRF could improve diagnostic and prognostic value. Objectives: The authors sought to evaluate the association of an augmented 6-minute incremental step test (6MIST) with standard CPET. Methods: We enrolled patients undergoing clinically indicated supine cycle ergometry CPET with invasive hemodynamics (iCPET) for the same-day 6MIST. CRF-related variables were simultaneously recorded using a signal morphology-based impedance cardiograph (PhysioFlow Enduro) and a portable metabolic analyzer (VO2 Master Pro) during incremental pace stationary stepping. The correlation between CPET and hemodynamic parameters from both tests was assessed using the intraclass correlation coefficient (ICC). Results: Fifteen patients (mean age 60 ± 14 years, 40% female, 27% Black) were included. All patients who agreed to undergo 6MIST completed the study without any test-related adverse events. We observed good to excellent correlation between iCPET- and 6MIST-measured CPET parameters: peak heart rate (ICC = 0.60; 95% CI: 0.15-0.85), absolute peak O2 consumption (VO2) (ICC = 0.77; 95% CI: 0.44-0.92), relative peak VO2 (ICC = 0.64; 95% CI: 0.20-0.86), maximum ventilation (ICC = 0.59; 95% CI: 0.13-0.84), O2 pulse (ICC = 0.71; 95% CI: 0.33-0.89), and cardiorespiratory optimal point (ICC = 0.82; 95% CI: 0.52-0.94). No significant correlation was determined between iCPET and 6MIST in measuring cardiac index at rest (ICC = 0.19; 95% CI: -0.34 to 0.63) or at peak exercise (ICC = 0.36; 95% CI: -0.17 to 0.73). Conclusions: We demonstrate the feasibility of a novel augmented 6MIST with wearable devices for simultaneous CPET and hemodynamic assessment. 6MIST-measured CPET parameters were strongly correlated with the iCPET-derived measurements. Additional studies are needed to confirm the validity of the 6MIST compared to standard upright CPET.

Two sides of the same runner! The association between biomechanical and physiological markers of endurance performance in distance runners.

BACKGROUND: The number of people who run to achieve competitive performance has increased, encouraging the scientific community to analyze the association of factors that can affect a runner performance. RESEARCH QUESTION: Is there association between running spatiotemporal and angular kinematics with the physiological markers of endurance performance during a cardiorespiratory exercise test? METHODS: This was an observational cross-sectional study with 40 distance runners simultaneously submitted to a running biomechanical analysis and cardiorespiratory exercise test on a treadmill. Mixed models were developed to verify the association between angular kinematic data obtained by the Movement Deviation Profile and the running spatiotemporal data with oxygen consumption and ventilatory thresholds. RESULTS: Spatiotemporal variables [.e., step frequency Odds Ratio 0.09 [0.06-0.12 95 % Confidence Interval], center of mass vertical displacement Odds Ratio 0.10 [0.07-0.14 95 % Confidence Interval], and step length [Odds Ratio -0.01 [-0.01 to -0.00 95 % Confidence Interval]] were associated with VO2. Also, step frequency Odds Ratio 1.03 [1.01-1.05 95 % Confidence Interval] was associated with the first ventilatory threshold, and angular running kinematics [Movement Deviation Profile analysis] Odds Ratio 1.47 [1.13-1.91 95 % Confidence Interval] was associated with peak of exercise during the cardiorespiratory exercise test. SIGNIFICANCE: Our findings demonstrated that: both higher step frequency and center of mass vertical displacement are associated with the increase of oxygen demand; step frequency is associated with the first ventilatory threshold, due to the entrainment mechanism and angular kinematic parameters are associated with peak aerobic speed. Future studies could also compare the biomechanical and physiological characteristics of different groups of distance runners. This could help identify the factors that contribute to oxygen demands during running and performance across different ages, genders, and levels of competition.

Usefulness of Inter-Hospital Heart Team Conference Based Collaborative Outpatient Cardiac Rehabilitation in Patients with Cardiovascular Disease.

An inter-hospital heart team conference based collaborative follow-up (FU) may facilitate outpatient cardiac rehabilitation (CR) programs, especially in hospitals without an outpatient CR center. Consecutive 145 patients with cardiovascular disease who received inpatient treatment at Yamagata University Hospital were divided into collaborative (n = 76) and same-hospital (n = 69) FU groups. In the collaborative FU group, patients received outpatient care at a university hospital and outpatient CR at different hospitals. In the same-hospital FU group, patients received outpatient care and outpatient CR at the same hospital other than the university hospital. The collaborative FU group held monthly 60-minute inter-hospital heart team conferences with CR specialists. No cardiovascular accidents occurred during the outpatient CR program in either group. Peak oxygen uptake VO2, anaerobic threshold, brain natriuretic peptide level, and left ventricular ejection fraction significantly improved in both groups. Kaplan-Meier analysis revealed no significant difference in prognosis between the collaborative and same-hospital FU groups (P = 0.246). Of the patients who had collaborative CR programs, 29 (38.2%) patients (37 consultations) were discussed at an inter-hospital heart team conference. Eighteen (48.6%) consultations were for issues related to continuing outpatient CR programs. Collaborative FU was as useful as same-hospital FU in terms of safety, efficacy, and prognosis in patients with cardiovascular disease. We conclude that regular inter-hospital heart team conferences are useful for facilitating collaboration among outpatient CR programs.

Cardiac repolarisation indices are associated with oxygen consumption during maximal exercise test in highly-trained cross-country skiers.

The objective of this study was to test the vectorelectrocardiographic T-wave characteristics for their associations with oxygen consumption (VO2) and physical performance during a maximal cardiopulmonary exercise test (CPET) in highly trained cross-country skiers. Male highly trained cross-country skiers (n = 30) performed the maximal CPET on the bicycle ergospirometric "Oxycon Pro" system with simultaneous oxygen consumption (VO2) and electrocardiogram recording. The measurements were done at rest; the stage preceding anaerobic threshold (preAnT); peak load; and recovery. The anaerobic threshold was estimated by respiratory exchange ratio. Physical performance was estimated by maximal oxygen consumption (VO2max/kg). VECG characteristics were calculated using Kors transformation procedure. During the test, the magnitudes of T-vector, Tx and Ty components decreased until preAnT, then stayed relatively stable until peak load, and reversed during recovery. In univariate linear regression analysis, T-vector amplitude and Tx, Ty and Tz magnitudes were associated with VO2/kg during the test (p < 0.010). The baseline T-vector characteristics were not associated with physical performance. At the preAnT stage, Tx and T-vector amplitude were associated with VO2max/kg (RC 12.70, 95% CI 0.68-24.73, p = 0.039 and RC 10.64, 95% CI 1.62-19.67, p = 0.023, respectively).

Exercise Intolerance Is Associated with Cardiovascular Dysfunction in Long COVID-19 Syndrome.

Background/Objectives: Cardiorespiratory complications are commonly reported among patients with long COVID-19 syndrome. However, their effects on exercise capacity remain inconclusive. We investigated the impact of long COVID-19 on exercise tolerance combining cardiopulmonary exercise testing (CPET) with resting echocardiographic data. Methods: Forty-two patients (55 ± 13 years), 149 ± 92 days post-hospital discharge, and ten healthy age-matched participants underwent resting echocardiography and an incremental CPET to the limit of tolerance. Left ventricular global longitudinal strain (LV-GLS) and the left ventricular ejection fraction (LVEF) were calculated to assess left ventricular systolic function. The E/e' ratio was estimated as a surrogate of left ventricular end-diastolic filling pressures. Tricuspid annular systolic velocity (SRV) was used to assess right ventricular systolic performance. Through tricuspid regurgitation velocity and inferior vena cava diameter, end-respiratory variations in systolic pulmonary artery pressure (PASP) were estimated. Peak work rate (WRpeak) and peak oxygen uptake (VO2peak) were measured via a ramp incremental symptom-limited CPET. Results: Compared to healthy participants, patients had a significantly (p < 0.05) lower LVEF (59 ± 4% versus 49 ± 5%) and greater left ventricular end-diastolic diameter (48 ± 2 versus 54 ± 5 cm). In patients, there was a significant association of E/e' with WRpeak (r = -0.325) and VO2peak (r = -0.341). SRV was significantly associated with WRpeak (r = 0.432) and VO2peak (r = 0.556). LV-GLS and PASP were significantly correlated with VO2peak (r = -0.358 and r = -0.345, respectively). Conclusions: In patients with long COVID-19 syndrome, exercise intolerance is associated with left ventricular diastolic performance, left ventricular end-diastolic pressure, PASP and SRV. These findings highlight the interrelationship of exercise intolerance with left and right ventricular performance in long COVID-19 syndrome.

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.

Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction.

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 (VO2) 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/VO2 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 VO2, 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 VO2 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 mLO2/dL blood; P<0.001). During single leg knee extension, there was no difference in peak leg VO2 (P=0.306), but the peripherally limited group had greater blood flow/VO2 ratio (P=0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO2/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/V̇O2 ratio and poor muscle diffusive capacity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844.

Effects of Different Visual Flow Velocities on Psychophysiological Responses During Virtual Reality Cycling.

INTRODUCTION: Virtual reality cycling (VRC) is simulated outdoor cycling with changes in scenery in virtual reality (VR) with rotating ergometer pedals. The speed at which the scenery changes, which is the visual flow velocity, can shift according to the same pedal rotation speed. OBJECTIVES: This study investigated the effects of different visual flow velocities on the psychophysiological responses of cyclists using the VRC. METHODS: Participants were asked to cycle for 20 min at 30% of their maximum exercise load under four conditions: (1) bicycle ergometer without VR (control), (2) VRC at normal visual flow velocity (VRC-normal), (3) VRC at 0.5 times the visual flow velocity of VRC-normal (VRC-slow), and (4) VRC at 1.5 times the visual flow velocity of VRC-normal (VRC-fast). The order of the four conditions was randomized in a counterbalanced design. The heart rate and rating of perceived exertion were recorded during the exercise. Participants graded their enjoyment of the task using the physical activity enjoyment scale (PACES). The measured data were analyzed by comparing the visual flow velocity conditions (VRC-slow, VRC-normal, and VRC-fast), and comparing the VRC and bicycle ergometer (VRC-normal and control). RESULTS: A total of 24 participants were enrolled in the study. There was a significant main effect observed in the PACES score (F(2,46)=20.129, p<0.001, partial η2=0.467). In the post-hoc test for the PACES, significant differences were found in the following combinations: VRC-normal > VRC-slow (p=0.005); VRC-fast > VRC-normal (p=0.003); and VRC-fast > VRC-slow (p<0.001). In the modified Borg scale for lower-limb fatigue, there were significant differences in time factor (F(2,46)=134.048, p<0.001, partial η2=0.854) and interaction effects (F(4,92)=3.156, p=0.018, partial η2=0.121). In the post-hoc test for the modified Borg scale, significant trends were found in the following combinations: VRC-normal > VRC-fast (p=0.068) and VRC-slow > VRC-fast (p=0.083). CONCLUSION: The results suggest that a slower visual flow velocity may reduce the enjoyment of exercise, whereas a faster visual flow velocity may make the exercise feel less fatigued and more enjoyable.

The validity of cardiopulmonary exercise testing for assessing aerobic capacity in neuromuscular diseases.

OBJECTIVES: To determine the content validity of cardiopulmonary exercise testing (CPET) for assessing peak oxygen uptake (VO2peak) in neuromuscular diseases (NMD). DESIGN: Baseline assessment of a randomized controlled trial. SETTING: Academic hospital. PARTICIPANTS: Eighty-six adults (age: 58.0 ± 13.9 years) with Charcot-Marie-Tooth disease (n=35), post-polio syndrome (n=26), or other NMD (n=25). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Workload, gas exchange variables, heart rate, and ratings of perceived exertion were measured during CPET on a cycle ergometer, supervised by an experienced trained assessor. Muscle strength of the knee extensors was assessed isometrically with a fixed dynamometer. Criteria for confirming maximal cardiorespiratory effort during CPET were established during 3 consensus meetings with an expert group. The percentage of participants meeting these criteria was assessed to quantify content validity. RESULTS: The following criteria were established for maximal cardiorespiratory effort; a plateau in oxygen uptake (VO2plateau) as primary criterion, or 2 out of 3 secondary criteria; 1) peak respiratory exchange ratio (RERpeak) ≥1.10, 2), peak heart rate (HRpeak) ≥85% of predicted maximal heart rate, and 3) peak rating of perceived exertion (RPEpeak) ≥17 on the 6-20 Borg scale. These criteria were attained by 71 participants (83%). VO2plateau, RERpeak ≥1.10, HRpeak ≥85%, and RPEpeak ≥17 were attained by respectively 31%, 73%, 69%, and 72% of the participants. Peak workload, VO2peak, and knee extension muscle strength were significantly higher, and body mass index was lower (all p<0.05), in participants with maximal cardiorespiratory effort compared to other participants. CONCLUSIONS: Most people with NMD achieved maximal cardiorespiratory effort during CPET. Therewith, this study provides high quality evidence of sufficient content validity of VO2peak as a maximal aerobic capacity measure. Content validity may be lower in more severely affected people with lower physical fitness.

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.

Predicting Future Athletic Performance in Young Female Road Cyclists Based on Aerobic Fitness and Hematological Variables.

PURPOSE: This study aimed to determine whether the initial levels of aerobic fitness and hematological variables in young female road cyclists are related to their athletic performance development during their careers. METHODS: Results of graded exercise tests on a cycle ergometer and total hemoglobin mass (tHb-mass) measurements were analyzed in 34 female road cyclists (age 18.6 [1.9] y). Among them, 2 groups were distinguished based on their competitive performance (Union Cycliste Internationale world ranking) over the following 8 years. Areas under the curve in receiver-operating-characteristic curves were calculated as indicators of elite-performance prediction. RESULTS: Initial graded exercise test variables (peak power, peak oxygen uptake, and power at 4 mmol/L blood lactate) were not significantly different in elite (n = 13) versus nonelite (n = 21) riders. In contrast, elite riders had higher tHb-mass expressed either in absolute measures (664 [75] vs 596 [59] g, P = .006) or normalized to body mass (11.2 [0.8] vs 10.3 [0.7] g/kg, P = .001) and fat-free mass (14.4 [0.9] vs 13.1 [0.9] g/kg, P < .001). Absolute and relative erythrocyte volumes were significantly higher in elite subjects (P ranged from < .001 to .006). Of all the variables analyzed, the relative tHb-mass had the highest predictive ability to reach the elite level (area under the curve ranged from .82 to .85). CONCLUSION: Measurement of tHb-mass can be a helpful tool in talent detection to identify young female road cyclists with the potential to reach the elite level in the future.

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.

Sigmoidal heart rate response pattern during exercise in patients with chronic heart failure.

BACKGROUND: Detailed heart rate (HR) response patterns during exercise in patients with heart failure and sinus rhythm remains uncertain. METHODS: We screened consecutive heart failure patients who underwent cardiopulmonary exercise tests at a large academic center from November 2013 to July 2023. HR response during exercise was statistically classified using logistic differential equation models. RESULTS: A total of 99 patients were included. Of them, 75 patients were assigned to "sigmoidal pattern" and the other 24 to "exponential pattern". Patients with the sigmoidal pattern were older and exhibited higher plasma B-type natriuretic peptide levels. Increases in HR and VO2/kg up to the anaerobic threshold level were not different between both patterns. However, beyond the threshold, the sigmoidal pattern group showed no further increase in HR and significantly lower VO2/kg than their counterparts (interactions for p<0.001). CONCLUSIONS: HR response during exercise in patients with heart failure and sinus rhythm was categorized into two unique groups: sigmoidal and exponential patterns. More detailed clarification of the sigmoidal pattern, potentially indicating sinus node dysfunction, should offer new clinical insights for chronotropic incompetence.

Evaluation of brachycephalic obstructive airway syndrome breeding test results in Finland from 2017 to 2022.

BACKGROUND: Brachycephalic obstructive airway syndrome (BOAS), observed in many flat-faced dog breeds, is one of the most urgent welfare problems in pedigree dogs. Various breeding schemes against BOAS have been implemented in many countries during recent years, but their impact on breed health remains unknown. The BOAS breeding test, used by the Finnish Kennel Club (FKC), includes an exercise component with a recovery assessment, BOAS grading by a veterinarian that evaluates upper respiratory signs before and after exercise, and a nostril stenosis assessment. The aim of our study was to evaluate BOAS breeding test results and estimate the heritability of the BOAS grade using parent-offspring regression from FKC data collected during 2017-2022. RESULTS: The majority (80%) of dogs (n = 957) participating in FKC BOAS testing were English Bulldogs, French Bulldogs, and Pugs. In 2022, 89-100% of the litters from these three breeds registered with the FKC had at least one parent tested for BOAS. The proportion of dogs failing the exercise test was highest in English Bulldogs (11%), followed by French Bulldogs (4%) and Pugs (3%). In these three breeds, moderate to severe BOAS signs were reported in 28%, 22% and 30% of dogs, respectively. The proportion of moderate to severe nostril stenosis was highest (71%) in Pugs, followed by French Bulldogs (55%), and English Bulldogs (40%). Estimates of heritability for BOAS grade were separately calculated for these three breeds and for all dogs, and the estimates were moderate to high, ranging from 0.39 to 0.58. CONCLUSIONS: The exercise test alone did not sufficiently identify dogs with moderate to severe BOAS signs. To better consider the complex nature of BOAS and breed differences, exercise tolerance, the severity of upper respiratory signs (BOAS grade) and nostril stenosis should all be assessed together in breeding animals. The heritability estimates for veterinary-assessed BOAS grade indicated that BOAS grade could be used in selective breeding to obtain less-affected offspring.

Assessment of cardiorespiratory fitness in Chinese patients with early to mid-stage Parkinson's disease.

PURPOSE: To evaluate cardiorespiratory fitness in patients with early to mid-stage Parkinson's disease by cardiopulmonary exercise test (CPET) on a stationary cycle ergometer. METHODS: To compare the differences in each index of the cardiopulmonary exercise test between the two groups of subjects; general data such as disease duration, medication use and exercise habits were also collected. RESULTS: (1) Finally, 36 Parkinson's disease patients and 12 healthy controls successfully completed the cardiopulmonary exercise test without any adverse events. (2) The V'O2peak, Metspeak, RERpeak, MVVpeak, Wpeak, HRpeak, HRpeak/pre, percentage of HRR-1 min decay > 12 bpm, SBPpeak in the Parkinson's disease group were lower than those in the control group (p < .05, each). Detailed data: V'O2peak (15.7 ± 4.5vs21.5 ± 3.6 ml/kg/min, p < .01), Metspeak (4.5 ± 1.3 vs 6.1 ± 1.0, p < .01), RERpeak (1.04 ± 0.10 vs 1.15 ± 0.10, p = .001), MVVpeak (37.22 ± 11.58 vs 53.00 ± 16.85L/min, p = .009), Wpeak (49.17 ± 29.72 vs 49.17 ± 29.72W, p < .01), HRpeak (111.08 ± 16.67 vs 111.08 ± 16.67bpm, p < .01), HRpeak/pre (71.19 ± 10.06 vs 96.00 ± 21.13, p = .002), percentage of HRR-1min decay > 12bpm (33.3% vs 100%, p < .01), systolic blood pressure (155.81 ± 31.83 vs 175.83 ± 17.84 mmHg, p = .01). (3) Divided Parkinson's disease patients into high V'O2peak group (V'O2peak ≥ 15 mL/kg/min) and low V'O2peak group (V'O2peak < 15 mL/kg/min). The age of patients, Hoehn-Yahr grade and incidence of symptom fluctuation in high V'O2peak group were lower (p < .05, respectively), percentage of males and percentage of HRR-1 min decay > 12 bpm were higher (p < .05, respectively); p < .05 is considered a statistically significant difference. Detailed data: age of patients(61.05 ± 6.93 vs 68.57 ± 7.99 years, p = .005), Hoehn-Yahr grade(1.75 ± 0.48 vs 2.18 ± 0.64, p = .028), incidence of symptom fluctuation (59.1 vs 92.9%, p = .03), percentage of males (77.7 vs 42.9%, p = .041), percentage of HRR-1 min decay > 12 bpm (50 vs 7.1%, p = .008). CONCLUSIONS: Cardiopulmonary exercise test was safe to perform and the cardiorespiratory fitness is significantly reduced in patients with early and middle stage Parkinson's disease. Patients with Parkinson's disease presented blunted heart rate and systolic blood pressure responses to exercise test. Females, older age, fluctuating symptoms, high H-Y staging and higher activities of daily living may be associated with lower oxygen uptake.

Follow-up of Cardiopulmonary Responses Using Submaximal Exercise Test in Older Adults with Post-COVID-19.

Background: Data on cardiopulmonary fitness in older adults in the longer term after coronavirus disease 2019 (COVID-19) are of interest as the time required for the full recovery of physical fitness after COVID-19 remains unclear. Some studies have reported that patients do not recover physical fitness for up to 6 or 12 months after COVID-19, whereas other studies have observed full recovery after 12-months. Therefore, this study evaluated and compared the cardiopulmonary responses induced by the 6-minute walk test (6MWT) and 1-minute sit-to-stand-test (STST) results at 3, 6, and 12 months in older adults with and without COVID-19. Methods: This study included 59 older adults with and without a history of COVID-19. The cardiopulmonary response parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse oxygen saturation (O2 sat), rate of perceived exertion (RPE), and leg fatigue were evaluated in the participants after 6MWT and 1-min-STST assessments. Results: Post-COVID-19, older adults showed statistically significant differences in HR, SBP, DBP, O2 sat, RPE, leg fatigue, 6MWT time, and 1-min-STST step numbers at 3, 6, and 12 months (P < 0.001). Moreover, older adults showed statistically significant differences in HR, SBP, DBP, RPE, leg fatigue, O2 sat, and 6MWT distance at 3 months post-COVID-19 compared with those in older adults without COVID-19 (P < 0.001). Conclusion: While older adults showed recovery of cardiopulmonary response parameters according to 6MWT and 1-min-STST findings at the 12-month follow-up post-COVID-19, these results of these measurements did not return to the values observed in older adults without COVID-19.

Heart rate vARiability and physical activity in inpatient treatMent of burnOut and DepressIon (HARMODI): protocol of a cross-sectional study with up to 8-week follow up.

INTRODUCTION: Chronic stress can cause an imbalance within the autonomic nervous system, thereby affecting cardiovascular and mental health. Physical activity (PA) may have a positive effect on the autonomic nervous system and stress-related disorders, such as depression and burnout. Heart rate variability (HRV) is a non-invasive marker of the autonomic nervous system. However, limited and inconsistent data exist on the exact relationship between HRV, PA and depression and burnout symptoms. The HARMODI study aims to explore whether HRV is a feasible marker of depression and burnout symptoms and aims to evaluate the role of PA in the treatment of stress-related disorders. METHODS AND ANALYSES: This is an observational study with a cross-sectional up to 8 week follow-up study design. A total of 153 patients, undergoing psychiatric inpatient treatment with burnout syndrome (Z73) and depressive episode (F32 or F33) or adjustment disorder (F43.2), will be recruited. Data on depression and burnout symptoms, HRV recordings (24-hour, supine, standing and exercise stress test), cognitive function, cardiorespiratory fitness, cardiovascular health, balance and strength will be collected at baseline (T1) and after up to 8 weeks (T2). Continuous data on PA and Ecological Momentary Assessments of exhaustion, mood and tension will be monitored daily throughout inpatient treatment. Multiple regression models, adjusted for potential confounders, will assess the association between HRV as the primary outcome, PA and depression and burnout severity score. ETHICS AND DISSEMINATION: The protocol has been approved by Swiss Ethics Committee, Cantonal Ethics Committee Zürich. Results of HARMODI will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05874856.

Protocol for the San Diego Nathan Shock Center Clinical Cohort: a new resource for studies of human aging.

INTRODUCTION: While it is well recognised that aging is a heterogeneous process, our understanding of the determinants of biological aging and its heterogeneity remains unclear. The San Diego Nathan Shock Center (SD-NSC) Clinical Cohort aims to establish a resource of biospecimens and extensive donor clinical data such as physical, cognitive and sensory function to support other studies that aim to explore the heterogeneity of normal human aging and its biological underpinnings. METHODS AND ANALYSIS: The SD-NSC Clinical Cohort is composed of 80 individuals across the adult human lifespan. Strict inclusion and exclusion criteria are implemented to minimise extrinsic factors that may impede the study of normal aging. Across three visits, participants undergo extensive phenotyping for collection of physical performance, body composition, cognitive function, sensory ability, mental health and haematological data. During these visits, we also collected biospecimens including plasma, platelets, peripheral blood mononuclear cells and fibroblasts for banking and future studies on aging. ETHICS AND DISSEMINATION: Ethics approval from the UC San Diego School of Medicine Institutional Review Board (IRB #201 141 SHOCK Center Clinical Cohort, PI: Molina) was obtained on 11 November 2020. Written informed consent is obtained from all participants after objectives and procedures of the study have been fully explained. Congruent with the goal of establishing a core resource, biological samples and clinical data are made available to the research community through the SD-NSC.

[Physiological assessment and management of post-COVID patients with normal cardiopulmonary imaging and functional tests]. / Valoración fisiológica y manejo de pacientes post-COVID con pruebas funcionales cardiopulmonares y de imagen normales.

OBJECTIVE: Contributing to elucidate the pathophysiology of dyspnoea and exertion intolerance in post-COVID syndrome patients with normal cardiopulmonary imaging and functional tests at rest, while determining their fitness and level of endurance in order to individualize working parameters for physical rehabilitation. MATERIAL AND METHODS: After an anamnesis and clinical examination at rest, 27 subjects (50±11.9 years) (14 women) with post-COVID syndrome of more than 6 months of evolution performed a continuous maximal-incremental graded cardiopulmonary exercise test (CPET) with breath-by-breath gas-exchange monitoring and continuous ECG registration, on an electromagnetically braked cycle ergometer. The values obtained were compared with those of reference, gender or controls, using the Chi-square, t-Student or ANOVA test. RESULTS: The clinical examination at rest and the CPET were clinically normal and without adverse events. Reasons for stopping exercise were leg discomfort. It is only worth noting a BMI=29.9±5.8kg/m2 and a basal lactate concentration of 2.1±0.7mmol/L. The physiological assessment of endurance showed the following results relative to predicted VO2máx: 1)peakVO2=80.5±18.6%; 2)VO2 at ventilatory threshold1 (VO2VT1): 46.0±12.9%; 3)VO2VT2: 57.2±16.4%; 4)working time in acidosis: 5.6±3,0minutes; and 5)maximum lactate concentration: 5.1±2.2mmol/L. CONCLUSIONS: The CPET identified limited aerobic metabolism and early increase in glycolytic metabolism as causes of dyspnoea and exercise intolerance, determined fitness for physical rehabilitation, and individualized it based on the level of endurance.