Peak Exercise Research Articles

THE EFFECTS OF DIFFERENT INTERDIALYTIC INTERVALS ON CARDIORESPIRATORY FITNESS ASSESSED WITH CARDIOPULMONARY EXERCISE TESTING IN HEMODIALYSIS PATIENTS

Objective: Long interdialytic interval in thrice-weekly hemodialysis is associated with excess cardiovascular and all-cause mortality risk. Impaired cardiorespiratory fitness is a strong predictor of mortality in hemodialysis. This study investigated differences in cardiorespiratory fitness assessed with cardiopulmonary exercise testing (CPET) between the end of the 2-day and the 3-day interdialytic interval. Design and method: A total of 28 hemodialysis patients, randomized in two different sequences of evaluation underwent CPET and spirometry examination at the end of the 2-day and the 3-day intervals. The primary outcome was the difference in oxygen uptake at peak exercise [VO2peak(ml/kg/min)] assessed with CPET. Volume status was assessed with interdialytic-weight-gain (IDWG), lung ultrasound, bioimpedance spectroscopy (BIS), and inferior vena cava measurements. A total of 14 age- and sex-matched controls were also evaluated. Results: Hemodialysis patients at the end of both 2-day and 3-day intervals presented lower values in all major CPET parameters than controls. VO2peak(ml/kg/min) was significantly higher at the end of the 2-day than the 3-day interval (15.24±4.18 vs 13.64±2.76;p<0.001); similar were the results for VO2peak(ml/min) (1188±257 vs 1074±224;p<0.001) and VO2peak(%predicted) (58.9±9.2 vs 52.3±8.6;p<0.001). Numerical but no statistically significant differences were detected in VO2-anaerobic-threshold(ml/kg/min) and VO2-anaerobic-threshold(ml/min) between the two time-points. Maximal work load (90.1±23.2 vs 79.3±25.1;p<0.001), exercise duration, HR at peak exercise and oxygen pulse also showed lower values at the end of the 3-day interval. FEV1 levels were similar between the two evaluations. Generalized-linear-mixed-model analysis including IDWG as random covariate attenuated the observed differences in VO2peak(ml/kg/min). Changes in BIS-derived overhydration indexes were moderately correlated with changes of VO2peak(ml/kg/min). Conclusions: The 3-day interval was associated with further impairment of VO2 at peak exercise. This effect was predominantly driven by excess fluid accumulation during the extra interdialytic day.

Cardiopulmonary Exercise Testing Predicts Postoperative Morbidity after Major Abdominal Cancer Surgeries: A Prospective Observational Study

Background and Aim: Cardiopulmonary exercise testing (CPET) has been shown to predict outcomes after major surgery. However, CPET performance and risk thresholds may vary geographically due to different body composition, nutritional status, anaemia, etc. This study aimed to investigate the relationship between preoperative CPET variables and in-hospital morbidity after abdominal cancer surgeries. Methods: In this prospective observational study, 142 patients aged 18–70 years, American Society of Anesthesiologists Physical Status II–III, underwent CPET preoperatively within 7 days of planned surgery. Oxygen uptake (VO2), ventilatory equivalents for carbon dioxide, heart rate (HR) and oxygen pulse (VO2/HR) were measured at anaerobic threshold (AT) and peak exercise (PE). Morbidity was assessed using the postoperative morbidity survey (POMS) postoperatively on days 3, 5 and 7. Receiver operating characteristic (ROC) curves were constructed to assess the optimal cut-offs for various CPET parameters. A multivariate logistic regression model was applied to test the relationship between CPET and postoperative morbidity. Results: After excluding patients who met the exclusion criteria, data from 109 participants were available for analysis. Forty-two patients (39%) suffered some morbidity postoperatively. VO2@AT (univariate odds ratio (OR) 1.36 [1.11–1.67] P = 0.002), sex (0.40 [0.17–0.99] P = 0.04), HR@AT (0.91 [0.94–0.99] P = 0.01), VO2/HR@AT (2.00 [1.42–2.80] P < 0.001) and VO2/HR@PE (2.04 [1.45–2.87] P < 0.001] were associated with postoperative morbidity. The final multivariate regression model contained VO2@AT (multivariate OR 1.25 [1.00–1.56] P = 0.04) and VO2/HR@PE (1.89 [1.34–11.09] P = 0.001). ROC curves revealed the optimal cut-off for VO2@AT as 11.9 ml/kg/min and VO2/HR@PE at 6.1 ml/beat. Conclusion: CPET parameters of oxygen uptake at AT and oxygen pulse at PE can predict morbidity in patients undergoing major abdominal onco-surgeries.

AORTIC STENOSIS AND HEART FAILURE: DIFFERENCES AND SIMILARITIES BEYOND PRESERVED EJECTION FRACTION

Objective: Degenerative aortic stenosis (AS) is highly prevalent in Western countries and shows a strong association with age and other cardiovascular risk factors such as arterial hypertension, diabetes mellitus, dyslipidaemia, and visceral obesity. The same risk factors are involved in the development of heart failure with preserved ejection fraction (HFpEF). Notwithstanding several similarities, patients with AS and preserved left ventricular ejection fraction (ASpEF) are not considered to actually have HFpEF. We sought to investigate the haemodynamic and metabolic features of patients with ASpEF both at rest and during physical effort and highlight similarities and differences with HFpEF. Design and method: We enrolled 148 patients with HFpEF, 150 with ASpEF (with at least moderate aortic transvalvular gradient), and 80 age- and sex-matched healthy controls. All patients received a comprehensive laboratory evaluation, a resting echocardiographic examination, and a combined cardiopulmonary-echocardiographic stress test. Patients with ASpEF who fulfilled the criteria for transcatheter aortic valve replacement (n=125) underwent cardiac computed tomography to measure aortic valve calcium score and volume. Results: Serum levels of N-terminal prohormone of brain natriuretic peptide were similar between HFpEF and ASpEF patients after excluding subjects with atrial fibrillation. As a marker of deregulated inflammation, epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and controls and was inversely related to peak oxygen consumption (VO2) in all subgroups (Figure). Furthermore, all patients showed a significant impairment in peak VO2 caused by a reduction in bith cardiac output (CO) and peripheral arteriovenous oxygen difference (AVO2diff). HFpEF patients displayed increased arterial stiffness, worse left ventricular-arterial coupling, and worse left atrial function. On the other hand, patients with ASpEF showed worse right ventricular-pulmonary arterial coupling. In ASpEF, disease severity, evaluated by aortic transvalvular peak velocity, mean gradient at rest and peak exercise, and aortic valve calcium score and volume, was directly related to EAT thickness. Conclusions: ASpEF shows substantial similarities to HFpEF. ASpEF could represent a separate phenotype in the spectrum of HFpEF; further and larger studies should investigate this hypothesis to give further insight into the pathophysiology of ASpEF.

ACUTE EXERCISE-INDUCED INFLAMMATORY AND THROMBOTIC RESPONSE IN HYPERTENSIVE PATIENTS

Objective: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. Design and method: After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Blood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity were measured. Results: All biomarkers increased with exercise, except PAI-1, which decreased (P<0.05 for the change between resting and peak exercise for all biomarkers). The normotensive group had less marked (P<0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P=NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%). Conclusions: In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. The effect of blood-pressure lowering treatment on the exercise-induced acute phase response remains to be elucidated.

Hypertension and Ventilatory Ineffciency During Exercise in the Fitness Registry and the Importance of Exercise National Database (FRIEND)

Background: Ventilatory ineffciency (high minute ventilation/rate of carbon dioxide production [V̇E/V̇CO2] slope) during exercise is more common in patients with metabolic syndrome and cardiovascular disease, and is prognostic of cardiovascular mortality. Interestingly, new data suggest that adults with controlled or untreated, but not uncontrolled, primary hypertension (HTN) have ventilatory ineffciency during exercise. However, the sample sizes were modest (n=~20/group). Therefore, we used a large database to test the hypothesis that adults with controlled or untreated, but not uncontrolled, primary HTN have higher V̇E/V̇CO2 slope than adults with no HTN. Methods: We used American Heart Association guidelines for HTN as systolic blood pressure [BP] ≥130mmHg, diastolic BP ≥80, or anti-HTN medication in the Fitness Registry and the Importance of Exercise National Database (FRIEND). To isolate primary HTN, we excluded those with any disease other than HTN, any medication use other than anti-HTN medication(s), current smoking status, and/or obesity (body mass index [BMI]≥30). The V̇E/V̇CO2 slope was determined from a peak cycling exercise test. We excluded adults with a peak respiratory exchange ratio <1.00 during exercise. All data are presented as median[IQR]. We compared groups using linear regression unadjusted and adjusted for sex, fitness, and age. Results: The sample (n=4,659) characteristics were age: 42[18] years old (range 18-91 years); 52% with HTN; 18% female; BMI: 26.0[4.0] kg/m2; cardiorespiratory fitness: 28.5[11.0] mL O2/kg/min; race/ethnicity: <1% American Indian, 3% Asian, 12% Black, 8% Hispanic, 4% Other, & 73% White. The V̇E/V̇CO2 slope during exercise was higher in adults without HTN (n=2,410; 24.9[3.8]) compared to those with uncontrolled HTN (n=252; 24.7[3.0]; standard error of the estimate[SE]: -0.20, 95% confidence interval[CI]: -0.33 to -0.07, p=0.003), but not controlled HTN (n=132; 24.4[3.4]; SE: -0.14, 95%CI: -0.31 to 0.04, p=0.12) or untreated HTN (n=1,865; 24.7[3.7]; SE: -0.05, 95%CI: -0.11 to 0.009, p=0.09) (model: R2=0.002, F3,4655=3.83, p=0.009). However, no pairwise differences were observed after covariate adjustment (model: R2=0.117, F6,4652=103, p<0.001). Conclusion: In contrast to our hypothesis, these data from the FRIEND indicate that primary HTN is not associated with ventilatory ineffciency (i.e., higher V̇E/V̇CO2 slope). National Institutes of Health K01HL160772 (JCW), American Heart Association 23CDA1037938 (JCW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of chronotropic incompetence on physiologic responses during progressive exercise in people with Parkinson’s disease

PurposeHeart rate (HR) response is likely to vary in people with Parkinson’s disease (PD), particularly for those with chronotropic incompetence (CI). This study explores the impact of CI on HR and metabolic responses during cardiopulmonary exercise test (CPET) in people with PD, and its implications for exercise intensity prescription.MethodsTwenty-eight participants with mild PD and seventeen healthy controls underwent CPET to identify the presence or absence of CI. HR and metabolic responses were measured at submaximal (first (VT1) and second (VT2) ventilatory thresholds), and at peak exercise. Main outcome measures were HR, oxygen consumption (VO2), and changes in HR responses (HR/WR slope) to an increase in exercise demand.ResultsCI was present in 13 (46%) PD participants (PDCI), who during CPET, exhibited blunted HR responses compared to controls and PD non-CI beyond 60% of maximal workload (p ≤ 0.05). PDCI presented a significantly lower HR at VT2, and peak exercise compared to PD non-CI and controls (p ≤ 0.001). VO2 was significantly lower in PDCI than PD non-CI and controls at VT2 (p = 0.003 and p = 0.036, respectively) and at peak exercise (p = 0.001 and p = 0.023, respectively).ConclusionAlthough poorly understood, the presence of CI in PD and its effect on HR and metabolic responses during incremental exercise is significant and important to consider when programming aerobic exercises.

Lean body mass and the cardiorespiratory phenotype: An ethnic-specific relationship in Hans Chinese women and men.

Lean body mass (LBM) and the functional capacity of cardiovascular (CV) and respiratory systems constitute a female-specific relationship in European-American individuals. Whether this recent finding be extrapolated to the world's largest ethnic group, that is, Hans Chinese (HC, a population characterized by low LBM), is unknown. Healthy HC adults (n=144, 50% ♀) closely matched by sex, age and physical activity were included. Total and regional (leg, arm and trunk) LBM and body composition were measured via dual-energy X-ray absorptiometry. Cardiac structure, stiffness, central/peripheral haemodynamics and peak O2 consumption (VO2peak) were assessed via transthoracic echocardiography and pulmonary gas analyses at rest and during exercise up to peak effort. Regression analyses determined the sex-specific relationship of LBM with cardiac and aerobic phenotypes. Total and regional LBM were lower and body fat percentage higher in women compared with men (P<0.001). In both sexes, total LBM positively associated with left ventricular (LV) mass and peak volumes (r≥0.33, P≤0.005) and negatively with LV end-systolic and central arterial stiffness (r≥-0.34, P≤0.004). Total LBM strongly associated with VO2peak (r≥0.60, P<0.001) and peak cardiac output (r≥0.40, P<0.001) in women and men. Among regional LBM, leg LBM prominently associated with the arterio-venous O2 difference at peak exercise in both sexes (r≥0.43, P<0.001). Adjustment by adiposity or CV risk factors did not modify the results. LBM independently determines internal cardiac dimensions, ventricular mass, distensibility and the capacity to deliver and consume O2 in HC adults irrespective of sex.

Determinants of physical quality of life in patients with chronic thromboembolic pulmonary hypertension after treatment: Insights from invasive exercise stress test

BackgroundImpaired quality of life (QoL) is prevalent among patients with chronic thromboembolic pulmonary hypertension (CTEPH) despite improved survival due to medical advances. We clarified the physical QoL of patients with CTEPH with mildly elevated pulmonary hemodynamics and evaluated its determinants using a database of patients with CTEPH evaluated for hemodynamics during exercise. MethodsThe QoL was measured in 144 patients with CTEPH (age, 66 (58-73) years; men/women, 48/96) with mildly elevated mean pulmonary artery pressure (< 30 mmHg) at rest after treatment with balloon pulmonary angioplasty and/or pulmonary endarterectomy using the Short-Form 36 (SF-36) questionnaire. The enrolled patients were divided into two groups: physical component summary (PCS) scores in the SF-36 over 50 as PCS-good and those under 50 as PCS-poor. ResultsThe median PCS in SF-36 score was 43.4 (IQR 32.4-49.5) points. The PCS-poor group (n = 110) was older and had lower exercise capacity and SaO2 during exercise. PCS scores were correlated with 6-minute walk distance (rs = 0.40, p < 0.001), quadriceps strength (rs = 0.34, p < 0.001), peak VO2 (rs = 0.31, p < 0.001), SaO2 at rest (rs = 0.35, p < 0.001) and peak exercise (rs = 0.33, p < 0.001), home oxygen therapy usage (rs = −0.28, p = 0.001), and pulmonary vascular resistance at peak exercise (rs = −0.26, p = 0.002). ConclusionsThe impairment of physical QoL was common in patients with CTEPH with improved hemodynamics; exercise capacity, hypoxemia, and hemodynamic status during exercise were related to the physical QoL.

Cardiopulmonary Exercise Testing in a Prospective Multicenter Cohort of Older Adults.

Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (V̇O 2peak ) declines with aging and correlates with mortality and morbidity. Cardiopulmonary exercise testing (CPET) is the criterion method to assess CRF, but its feasibility, validity, and reliability in older adults are unclear. Our objective was to design and implement a dependable, safe, and reliable CPET protocol in older adults. V̇O 2peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 yr in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria (V̇O 2peak <12.0 mL·kg -1 ·min -1 ; maximum heart rate <100 bpm; respiratory exchange ratio <1.05 and a rating of perceived exertion <15). A subset ( N = 30) performed a repeat test to assess reproducibility. CPET was safe and well tolerated, with 95.8% of participants able to complete the V̇O 2peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD V̇O 2peak was 20.2 ± 4.8 mL·kg -1 ·min -1 , peak heart rate 142 ± 18 bpm, and peak respiratory exchange ratio 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid and 27 as invalid (18 data collection errors, 9 did not reach V̇O 2peak ). Reproducibility of V̇O 2peak was high (intraclass correlation coefficient = 0.97). CPET was feasible, effective, and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.

SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension.

This study aims to assess the impact of sotatercept on exercise tolerance, exercise capacity, and right ventricular function in pulmonary arterial hypertension. SPECTRA (Sotatercept Phase 2 Exploratory Clinical Trial in PAH) was a phase 2a, single-arm, open-label, multicenter exploratory study that evaluated the effects of sotatercept by invasive cardiopulmonary exercise testing in participants with pulmonary arterial hypertension and World Health Organization functional class III on combination background therapy. The primary end point was the change in peak oxygen uptake from baseline to week 24. Cardiac magnetic resonance imaging was performed to assess right ventricular function. Among the 21 participants completing 24 weeks of treatment, there was a significant improvement from baseline in peak oxygen uptake, with a mean change of 102.74 mL/min ([95% CIs, 27.72-177.76]; P=0.0097). Sotatercept demonstrated improvements in secondary end points, including resting and peak exercise hemodynamics, and 6-minute walk distance versus baseline measures. Cardiac magnetic resonance imaging showed improvements from baseline at week 24 in right ventricular function. The clinical efficacy and safety of sotatercept demonstrated in the SPECTRA study emphasize the potential of this therapy as a new treatment option for patients with pulmonary arterial hypertension. Improvements in right ventricular structure and function underscore the potential for sotatercept as a disease-modifying agent with reverse-remodeling capabilities. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03738150.

The effect of anabolic androgenic steroids on heart rate recovery index and electrocardiographic parameters in male bodybuilders

BackgroundThe control of the cardiovascular system depends on the autonomic nerve system. Chronic anabolic andorogenic steroids (AAS) use causes sympathovagal imbalance and increases sympathetic nerve activity. ObjectiveThe reduction in heart rate from the peak exercise rate following the end of the exercise stress test is known as the heart rate recovery index (HRRI). Several methods have been utilized to assess myocardial repolarization, such as QT interval (QT), corrected QT interval (QTc), and T-wave peak-to-end interval (Tp-e interval). Based on a growing number of data a higher Tp-e/QT ratio is linked to malignant ventricular arrhythmias, and an increased Tp-e interval may correlate with the transmural dispersion of repolarization. Our hypothesis is that the use of chronic AAS was decrease HRRI during maximal exercise and increased risk of cardiac arrhythmias and sudden cardiac death. MethodsThis study included 44 male bodybuilders, with an average age of 29.7 ± 8.14 years, divided into AAS abuse [AAS users (n = 21) and AAS nonuser (n = 23)]. ResultsThe first (p = 0.001) and second minute (p = 0.001) HRRI of the subjects with AAS users were significantly lower than those of the control group. Additionally, HRRI after the third (p = 0.004) and fifth minutes (p = 0.007) of the recovery period were significantly lower in AAS group compared with the control group. Who used AAS had significantly higher QT, QTc, Tp-e, Tp-e/QT, and Tp-e/QTc values than non-users (all p = 0.001). ConclusionsChronic AAS use has been shown to cause sympathetic dominance, which may be a pro arrhythmic state.

Novel wireless laser doppler flowmeter-based investigation of earlobe vascular dynamics in cardiopulmonary exercise testing.

[Purpose] A new wireless laser Doppler blood flowmeter has facilitated easier, more stable measurement of skin perfusion during exercise. However, earlobe blood flow during the cardiopulmonary exercise test remains unascertained. This study aimed to clarify the characteristics of earlobe blood flow during incremental exercise load in healthy individuals. [Participants and Methods] Among 25 healthy males (age 23.6 ± 2.5 years), cycle ergometer-based symptom-limited cardiopulmonary exercise test, after 4 minutes of rest, was conducted with a 4-minute 20W warm-up and a continuous 2W-increase in the work rate every 6 seconds; earlobe blood flow was measured using a wireless laser Doppler blood flowmeter. [Results] Compared with that at rest, earlobe blood flow increased significantly from 50% of exercise peak intensity to a maximum of 1.7 times, but decreased immediately after exercise. The earlobe blood flow %change did not significantly correlate with hemodynamic parameters and its inflection point 36.4% Loadpeak was significantly lower than the anaerobic metabolic threshold 58.1% Loadpeak. [Conclusion] In healthy participants, earlobe blood flow during cardiopulmonary exercise test increased gradually with low-intensity exercise from approximately 1.5 times the resting rate and approached the anaerobic metabolic threshold with a maximum of 1.7 times the resting earlobe blood flow, but decreased quickly after exercise.

Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.

Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650.

Aerobic capacity and mitochondrial function in bipolar disorder: a longitudinal study during acute phases and after clinical remission.

Aerobic capacity has shown to predict physical and mental health-related quality of life in bipolar disorder (BD). However, the correlation between exercise respiratory capacity and mitochondrial function remains understudied. We aimed to assess longitudinally intra-individual differences in these factors during mood episodes and remission in BD. This study included eight BD patients admitted to an acute psychiatric unit. Incremental cardiopulmonary exercise test (CPET) was conducted during acute episodes (T0), followed by constant work rate cycle ergometry (CWRCE) to evaluate endurance time, oxygen uptake at peak exercise (VO2peak) and at the anaerobic threshold. The second test was repeated during remission (T1). Mitochondrial respiration rates were assessed at T0 and T1 in peripheral blood mononuclear cells. Endurance time, VO2peak, and anaerobic threshold oxygen consumption showed no significant variations between T0 and T1. Basal oxygen consumption at T1 tended to inversely correlate with maximal mitochondrial respiratory capacity (r=-0.690, p=0.058), and VO2peak during exercise at T1 inversely correlated with basal and minimum mitochondrial respiration (r=-0.810, p=0.015; r=-0.786, p=0.021, respectively). Our preliminary data showed that lower basal oxygen consumption may be linked to greater mitochondrial respiratory capacity, and maximum oxygen uptake during the exercise task was associated with lower basal mitochondrial respiration, suggesting that lower oxygen requirements could be associated with greater mitochondrial capacity. These findings should be replicated in larger samples stratified for manic and depressive states.

Adaptation to Living at High Altitude in Patients with COPD. Comparative Study of Exercise Capacity and Ventilatory Variables between Patients Residing at High and Low Altitudes in the Andes.

González-García, Mauricio and Luis Ernesto Téllez. Adaptation to living at high altitude in patients with COPD. Comparative study of exercise capacity and ventilatory variables between patients residing at high and low altitudes in the Andes. High Alt Med Biol. 00:000-000, 2024. Introduction: Although some variables related to oxygen transport and utilization such as ventilation, pulmonary vascular responses to hypoxia, heart rate (HR), cardiac output, hemoglobin (Hb), and oxygen saturation (SpO2) are used to compare adaptation to altitude between populations, peak oxygen consumption (VO2) constitutes an integrative measure of total oxygen transport that may reflect successful adaptation to altitude. We designed this study to make a direct comparison of VO2 in a cardiopulmonary exercise test (CPET) between chronic obstructive pulmonary disease (COPD) patients residing at high altitude (Bogotá, Colombia: 2,640 m) (COPD-HA) and those living at low altitude (Bucaramanga, Colombia: 959 m) (COPD-LA). Methods: All patients performed a CPET with measurements of VO2, minute ventilation (VE), HR, oxygen pulse (VO2/HR), ventilatory equivalents (VE/VCO2), and SpO2. Unpaired T-test or Mann-Whitney U test were used for comparisons between COPD-HA and COPD-LA. Results: We included 71 patients with COPD, 53 COPD-HA, and 18 COPD-LA. There were no differences between groups in age, sex, or forced expiratory volume in 1 second. The means ± SD of Hb, g/dl was slightly higher in COPD-HA (15.9 ± 1.9 vs. 14.7 ± 1.8, p = 0.048), without differences in VO2, % pred (71.6 ± 17.9 vs. 69.0 ± 17.0, p = 0.584), VO2/HR, % pred (92.1 ± 22.0 vs. 89.7 ± 19.8, p = 0.733) or VE/MVV, % (75.5 ± 14.1 vs. 76.5 ± 14.3, p = 0.790) at peak exercise between groups. Median (IQR) of VE/VCO2 nadir [38.0 (37.0-42.0) vs. 32.5 (31.0-39.0), p = 0.005] was significantly higher, and SpO2, % at rest [88.0 (86.0-91.0) vs. 95.0 (94.0-96.0), p < 0.001] and at peak exercise [84.0 (77.0-90.0) vs. 93.0 (92.0-95.0), p < 0.001] were significantly lower in COPD-HA. Conclusions: Despite higher desaturation at rest and during exercise in COPD-HA, there were no differences in VO2 peak between COPD-HA and COPD-LA, suggesting a potential altitude adaptation in those patients chronically exposed to hypoxia.

Physiological determinants of decreased peak leg oxygen uptake in chronic disease: a systematic review and meta-analysis.

This systematic review and meta-analysis examined the physiological mechanisms responsible for lower peak exercise leg oxygen uptake (V̇o2) in patients with chronic disease. Studies measuring peak leg V̇o2 (primary outcome) and its physiological determinants during large (cycle) or small muscle mass exercise (single-leg knee extension, SLKE) in patients with chronic disease were included in this meta-analysis. Pooled estimates for each outcome were reported as a weighted mean difference (WMD) between chronic disease and controls. We included 10 studies that measured peak leg V̇o2 in patients with chronic disease (n = 109, mean age: 45 yr; encompassing chronic obstructive pulmonary disease, COPD, heart failure with reduced ejection fraction, HFrEF, or chronic renal failure, RF) and age-matched controls (n = 88). In pooled analysis, peak leg V̇o2 (WMD; -0.23 L/min, 95% CI: -0.32 to -0.13), leg oxygen (O2) delivery (WMD: -0.27 L/min, 95% CI: -0.37 to -0.17), and muscle O2 diffusive conductance (WMD: -5.2 mL/min/mmHg, 95% CI: -7.1 to -3.2) were all significantly lower during cycle and SLKE exercise in chronic disease versus controls. These results highlight that during large and small muscle mass exercise in patients with COPD, HFrEF, or RF, there is no single factor causing peak V̇o2 limitations. Specifically, the lower peak V̇o2 in these pathologies is due to not only the expected impairments in convective O2 delivery but also impairments in muscle oxygen diffusive transport from capillary to mitochondria. Whether impaired muscle O2 transport is caused solely by inactivity or additional muscle pathology remains in question.NEW & NOTEWORTHY Peripheral (skeletal muscle and vasculature) factors contribute significantly to reduced exercise capacity during both large and small muscle mass exercise in chronic diseases such as COPD, HFrEF, or RF and should be important targets of therapy in addition to the primary organs (lungs, heart, and kidneys) affected by disease.

Association of childhood socioeconomic status with adulthood maximal exercise blood pressure: the Cardiovascular Risk in Young Finns Study

Purpose Socioeconomic status has been related to resting blood pressure (BP) levels at different stages of life. However, the association of childhood socioeconomic status (SES) and adulthood exercise BP is largely unknown. Therefore, we studied the association of childhood SES with adulthood maximal exercise BP. Materials and methods This investigation consisted of 373 individuals (53% women) participating in the Cardiovascular Risk in Young Finns Study who had data concerning family SES in childhood (baseline in 1980, at age of 6–18 years) and exercise BP response data in adulthood (follow-up in adulthood in 27–29 years since baseline). A maximal cardiopulmonary exercise test with BP measurements was performed by participants, and peak exercise BP was measured. Results In stepwise multivariable analysis including childhood risk factors and lifestyle factors (body mass index, systolic BP, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, fruit consumption, vegetable consumption, and physical activity), lower family SES in childhood was associated with higher maximal exercise BP in adulthood (β value ± SE, 1.63 ± 0.77, p = 0.035). The association remained significant after further adjustment with participants SES in adulthood (β value ± SE, 1.68 ± 0.65, p = 0.011) and after further adjustment with adulthood body-mass index, systolic BP, maximal exercise capacity, and peak heart rate in exercise (β value ± SE, 1.25 ± 0.56, p = 0.027). Conclusions These findings suggest that lower childhood family SES is associated with higher maximal exercise BP in adulthood.

Long-term outcomes of extracardiac Gore-Tex conduits in Fontan patients

BackgroundExtracardiac conduit Fontan procedure (ECFP) employing a Gore-Tex conduit has been widely used for patients with single ventricle physiology; however, the long-term status of the conduit is unknown. We investigated the changes in a Gore-Tex conduit after ECFP and the factors associated with its narrowing. MethodsWe conducted a retrospective analysis of 86 patients who underwent ECFP between January 1995 and December 2008 and had cardiac computed tomography (CT) during the follow-up period. ResultsThe median patient age at ECFP was 2.8 years (range 1.6–9.7), and a cardiac CT was obtained at 13.1 ± 3.4 years later. The minimum conduit area decreased by approximately two-thirds of the original due to calcification, pseudointimal hyperplasia, thrombus, and luminal irregularity. The normalized minimum conduit area was influenced by the time interval from ECFP and normalized original conduit area at ECFP. An oversized conduit was associated with a narrowing of both its sides and a high frequency of pseudointimal hyperplasia or mural thrombus. The ratio of minimum conduit-to-inferior vena cava areas was lower in patients with chronic liver disease than in those with a normal liver. The maximum percent stenosis of the conduit correlated with oxygen pulse and heart rate during peak exercise. ConclusionsUsing a larger conduit at ECFP resulted in a larger minimum conduit area at follow-up. However, oversizing requires careful monitoring for stenosis near anastomotic sites and the occurrence of pseudointimal hyperplasia or thrombus.

Cardiopulmonary exercise testing and body composition.

The cardiopulmonary exercise test (CPET) evaluates cardiopulmonary function. In light of the obesity epidemic, it is important to understand how body composition affects interpretation of CPET results. The aim of the present study was to assess the relationship between CPET measures, other than peak oxygen uptake, and body composition. A total of 330 participants, aged 50 years, performed both a CPET and dual-energy X-ray absorptiometry (DXA). From the CPET, peak exercise respiratory exchange ratio (RER), ventilatory efficiency (V̇ E/V̇ CO2 slope) and work efficiency (ΔV̇ O2 /ΔWR) were recorded. Pearson's correlation was used to assess the association between CPET measures and selected body composition measures, including body mass index (BMI), waist circumference, fat mass, lean mass, body fat percentage and percentage trunk fat to fat mass. All analyses were done stratified by sex. A p-value <0.05 defined statistical significance. RER was negatively correlated with body composition measures; the strongest correlation was observed with waist circumference in females (r= -0.36). V̇ E/V̇ CO2 slope had no significant correlations with any body composition measures. ΔV̇ O2 /ΔWR was positively correlated with the body composition measures; the strongest correlation was observed with BMI (r=0.24). The additive role of percentage body fat and percentage trunk fat were studied in a linear regression model using waist circumference and BMI to predict the aforementioned CPET measures and no additive role was found. RER and ΔV̇ O2 /ΔWR may be influenced by body composition while V̇ E/V̇ CO2 slope is not affected. Adiposity measures from DXA add no additional explanatory value to the CPET measures.

Metabolic cost of unloading pedalling in different groups of patients with pulmonary hypertension and volunteers

Recently, the parameter internal work (IW) has been introduced as change in oxygen uptake (VO2) between resting and unloading workload in cardiopulmonary exercise testing (CPET). The proportional IW (PIW) was defined as IW divided by VO2 at peak exercise. A second option is to calculate the PIW based on the workload [PIW (Watt)] by considering the aerobic efficiency. The aim of our study was to investigate whether IW and PIW differ between patients with and without pulmonary hypertension and healthy controls. Our study population consisted of 580 patients and 354 healthy controls derived from the Study of Health in Pomerania. The PIW was slightly lower in patients (14.2%) than in healthy controls (14.9%; p = 0.030), but the PIW (Watt) was higher in patients (18.0%) than in the healthy controls (15.9%; p = 0.001). Such a difference was also observed, when considering only the submaximal workload up to the VAT (19.8% in patients and 15.1% in healthy controls; p < 0.001). Since the PIW (Watt) values were higher in patients with pulmonary hypertension, this marker may serve as a useful CPET parameter in clinical practice. In contrast to most of the currently used CPET parameters, the PIW does not require a maximal workload for the patient. Further studies are needed to validate the prognostic significance of the PIW.