Peak O2 Research Articles

Exercise feature and predictor of prognosis in patients with pulmonary artery stenosis-associated pulmonary hypertension.

The prognosis is poor for patients with pulmonary artery stenosis-associated pulmonary hypertension (PAS-PH). Identifying predictors of prognosis in PAS-PH is crucial to preventing premature death, which has rarely been investigated. We aimed to explore the cardiopulmonary exercise testing (CPET) parameters to predict the prognosis of these patients. We prospectively included all patients with PAS-PH who underwent CPET between September 2014 and June 2021 in Fuwai Hospital (ClinicalTrials.gov ID: NCT02061787). The primary outcome was clinical worsening, including death, rehospitalization for heart failure, or deterioration of PH. Seventy-two patients were included in this study. A median of 2-year follow-up revealed that 18 (25%) patients experienced clinical worsening. The 1-year, 3-year, and 5-year event-free survival rates were 92.5%, 81.7%, and 62.7%, respectively. Patients with clinical worsening demonstrated significantly worse baseline haemodynamics and poorer exercise capacity than their counterparts. Multivariable Cox regression identified that peak O2 pulse could independently predict clinical worsening [hazard ratio: 0.344, 95% confidence interval (CI) 0.188-0.631, P<0.001], outperforming other parameters. Peak O2 pulse correlated with PH severity. Incorporating peak O2 pulse into the simplified 2015 European Society of Cardiology/European Respiratory Society risk stratification improved the accuracy for predicting clinical worsening (pre vs. post area under the curve: 0.727 vs. 0.846, P<0.001; net reclassification index: 0.852, 95% CI 0.372-1.332, P<0.001; integrated discrimination index 0.133, 95% CI 0.031-0.235, P=0.011). The prognosis is poor for PAS-PH, and exercise intolerance and ventilation inefficiency are commonly observed. Peak O2 pulse independently predicted the prognosis of these patients. A low peak O2 pulse identified patients at high risk of clinical deterioration and served for risk stratification of PAS-PH.

Functional Capacity And Quality Of Life In Patients With Vascular Ring

Background: Vascular rings are congenital anomalies of the aortic arch that compress the trachea and esophagus and may require corrective surgery. Data about the long-term effects of vascular rings are scarce. We aimed to evaluate the long-term cardiorespiratory, exercise capacity and quality of life of vascular ring patients. Methods: A single center prospective study evaluating spirometry, echocardiography, six-minute walk test (6MWT), cardiopulmonary exercise testing (CPET) and quality of life questionnaire (SF36) in patients with a diagnosis of vascular ring, with or without corrective surgery. Results: Twenty-seven patients participated (11.9 ± 6 years, 52% males). The most common diagnosis was double aortic arch (16 patients, 59%). Nineteen patients had corrective surgery (O) and eight did not (NO). Pulmonary function tests were within normal range in both groups (FEV1% predicted O = 87.6 ± 16.5, NO = 83 ± 10.8%). However, 11/ 27 had abnormal FEV1, five had abnormal FVC and 13 (48%) had flattening of the expiratory curve. 6MWD and oxygen uptake were similarly mildly reduced in both groups; (6MWD O = 80.1 ± 10.7% predicted, NO = 74.1 ± 10.9% and oxygen uptake O = 78.5 ± 23.2% predicted, NO = 73.4 ± 14.3%). Peak O2 pulse (V̇O2/HR% predicted) was mildly reduced in the NO group (O = 88.4 ± 17.3%, NO = 75.8 ± 16.2%). Echocardiogram and SF36 scores were normal in all patients. Conclusions: Long-term evaluation of patients born with vascular rings revealed mild pulmonary impairment, reduction in 6MWD and oxygen uptake. The NO group had also mild reduced peak O2 pulse. Larger, long-term studies assessing functional parameters in operated and non-operated patients are needed to assess disease/surgery limitation in patients with vascular rings.

Right ventricular-pulmonary arterial coupling impairment and exercise capacity in obese adults.

BackgroundObesity-related exercise intolerance may be associated with pulmonary vascular and right ventricular dysfunction. This study tested the hypothesis that decreased pulmonary vascular reserve and right ventricular (RV)-pulmonary arterial (PA) uncoupling contributes to exercise limitation in subjects with obesity.MethodsSeventeen subjects with obesity were matched to normo-weighted healthy controls. All subjects underwent; exercise echocardiography, lung diffusing capacity (DL) for nitric oxide (NO) and carbon monoxide (CO) and an incremental cardiopulmonary exercise test. Cardiac output (Q), PA pressure (PAP) and tricuspid annular plane systolic excursion (TAPSE) were recorded at increasing exercise intensities. Pulmonary vascular reserve was assessed by multipoint mean PAP (mPAP)/Q relationships with more reserve defined by lesser increase in mPAP at increased Q, and RV-PA coupling was assessed by the TAPSE/systolic PAP (sPAP) ratio.ResultsAt rest, subjects with obesity displayed lower TAPSE/sPAP ratios (1.00 ± 0.26 vs. 1.19 ± 0.22 ml/mmHg, P < 0.05), DLCO and pulmonary capillary blood volume (52 ± 11 vs. 64 ± 13 ml, P < 0.01) compared to controls. Exercise was associated with steeper mPAP-Q slopes, decreased TAPSE/sPAP and lower peak O2 uptake (VO2peak). The changes in TAPSE/sPAP at exercise were correlated to the body fat mass (R = 0.39, P = 0.01) and VO2peak (R = 0.44, P < 0.01).ConclusionObesity is associated with a decreased pulmonary vascular and RV-PA coupling reserve which may impair exercise capacity.

Evaluation of a Hybrid Cardiovascular Rehabilitation Program in Acute Coronary Syndrome Low-Risk Patients Organised in Both Cardiac Rehabilitation and Sport Centres: A Model Feasibility Study.

The aim of the study was to investigate the efficiency, the feasibility, and the safety of a hybrid cardiovascular rehabilitation program in low-risk acute coronary syndrome (ACS) patients. Sixty low-risk patients with stable clinical status who experienced an ACS in the previous 3 months were included in a 3-week rehabilitation program. The patients were randomized either to a group performing the rehabilitation totally in a rehabilitation centre or partially (only the first 5 days) and then in sport centres equipped for supervised adapted physical activities. The sport centres were located in the vicinity of the patient’s home. Both rehabilitation programs entailed endurance and resistance training and educational therapy. Before and after rehabilitation, cardiorespiratory functions were measured. Similar and significant improvements in peak O2 and power output were seen in patients after both types of rehabilitation (p < 0.05). No particular complications were associated with both of our programs. We conclude that a hybrid rehabilitation program in low-risk ACS patients is feasible, safe, and as beneficial as a traditional program organised in a rehabilitation centre, at least in a short-term. A longitudinal follow-up should nevertheless be organised to examine the long-term impacts of this hybrid rehabilitation program.

Longitudinal assessment of cardiorespiratory fitness and body mass of young healthy adults during COVID-19 pandemic.

Physical activity was reduced during the COVID-19 pandemic, especially when lockdowns were mandated; however, little is known about the impact of these lifestyle changes on objective measures of cardiorespiratory fitness. To address this knowledge gap, we evaluated the cardiorespiratory fitness of 14 young healthy adults (4 women, age: 27 ± 6 yr) just before the pandemic and after ∼1 yr of public health measures being in place. During fitness assessments, participants performed submaximal pseudorandom cycling exercise to assess cardiorespiratory kinetics, and a 25 W·min-1 ramp-incremental cycling test to determine peak oxygen uptake (V̇o2). Cluster analysis identified two subgroups of participants: those who had reduced peak V̇o2 at the 1-yr follow-up (-0.50 ± 0.17 L·min-1) and those whose peak V̇o2 was maintained (0.00 ± 0.10 L·min-1). Participants with reduced peak V̇o2 also exhibited slower heart rate kinetics (interaction: P = 0.01), reduced peak O2 pulse (interaction: P < 0.001), and lower peak work rate (interaction: P < 0.001) after 1 yr of the pandemic, whereas these variables were unchanged in the group of participants who maintained peak V̇o2. Regardless of changes in peak V̇o2, both subgroups of participants gained body mass (main effect: P = 0.002), which was negatively correlated with participants' level of self-reported physical activity level at the follow-up assessment (mass: ρ = -0.59, P = 0.03) These findings suggest that some young healthy individuals lost cardiorespiratory fitness during the pandemic, whereas others gained weight, but both changes could potentially increase the risk of adverse health outcomes and disease later in life if left unaddressed.NEW & NOTEWORTHY Some young healthy adults experienced cardiovascular deconditioning during the COVID-19 pandemic, with measurable reductions in cardiorespiratory fitness, whereas others experienced no change in fitness but gained body mass, which was related to self-reported physical activity during the pandemic.

Echocardiographic myocardial work in pre-adolescent male basketball players: a comparison with cardiopulmonary exercise test-derived aerobic capacity.

Background: Pressure-strain loop (PSL) analysis provides a novel, less load-dependent non-invasive method to quantify myocardial work and demonstrates a significant correlation with the contractile reserve in adult athletes. We aim to validate PSL-derived markers in characterizing LV function in pre-adolescent basketball players by comparing results before and after the cardiopulmonary exercise test (CPX) and explore its association with CPX-derived aerobic capacity. Methods: Cardiac morphology and function in 20 pre-adolescent basketball players were assessed at 9.7 years old (9.7 ± 1.1 year) before and after cardiopulmonary exercise testing. Echocardiography was performed in all subjects, including two-dimensional speckle-tracking echocardiography (STE). Simultaneous brachial-cuff-measured blood pressure was recorded to perform PSL analysis. Results: Nineteen subjects were included in the final analysis. Exercise training in pre-adolescent males was associated with lower global work index (GWI) and global work efficiency (GWE) at rest. GWE at stress was significantly correlated with VO2max and peak O2 pulse (p = 0.0122, r = 0.56; p = 0.00122, r = 0.69, respectively). When indexed by body mass, GWI and GWE both significantly correlated with relative VO2max (p = 0.0086 and 0.0011 respectively, r = 0.58 and 0.69 respectively); GWI and GWE at baseline and stress were all significantly correlated with peak O2 pulse (GWI at baseline, p < 0.0001, r = −0.90; GWE at baseline, p < 0.0001, r = −0.89; GWI at stress, p = 0.0289, r = −0.50; GWE at stress, p < 0.0001, r = −0.83). Conclusion: PSL-analysis-derived GWI and GWE at rest indexed by body mass are associated with cardiopulmonary exercise test-derived peak oxygen consumption and oxygen pulse in pre-adolescent athletes.

Assessment of Metabolic Flexibility by Substrate Oxidation Responses and Blood Lactate in Women Expressing Varying Levels of Aerobic Fitness and Body Fat.

Waldman, HS, Bryant, AR, Knight, SN, Killen, LG, Davis, BA, Robinson, MA, and O'Neal, EK. Assessment of metabolic flexibility by substrate oxidation responses and blood lactate in women expressing varying levels of aerobic fitness and body fat. J Strength Cond Res 37(3): 581-588, 2023-Collection of substrate oxidation responses during exercise is proposed as a noninvasive means for assessing metabolic flexibility in male subjects. However, because of hormonal and metabolic differences between sexes, this method may not be applicable to female subjects. This study assessed metabolic flexibility through indirect calorimetry across female subjects with different maximal oxidative capacities. Thirty-eight (18-45 years) eumenorrheic female subjects were stratified ( p < 0.05) based on V̇ o2 peak (mL·kg -1 ·min -1 ) into (1) endurance-trained (ET, n = 12, 42.6 ± 5.3), (2) recreationally active (RA, n = 13, 32.3 ± 1.6), or (3) overweight female subjects (OW, n = 13, 21.0 ± 4.0). Subjects completed the same 5-stage graded exercise test with intensities of 30, 45, 60, 75, and 90 W. Lactate [La - ], carbohydrate (CHOox), and fat (FATox) oxidation rates were assessed during the last min of each 5-minute stage. Subjects then cycled to exhaustion to determine V̇ o2 peak. Endurance-trained and RA female subjects expressed significantly ( p ≤ 0.05) higher absolute rates and rates scaled to fat-free mass of CHOox and FATox compared with OW female subjects during multiple stages. [La - ] failed to consistently differentiate the 3 groups with higher [La - ] for OW only found during stage 4; however, RER differed by 0.09 units or more at each stage for OW vs. ET. It seems that RER was more sensitive to cohort characteristics than [La - ] contrasting recent findings in male cohorts. In conclusion, indirect calorimetry is a practical and noninvasive method for assessing metabolic flexibility in eumenorrheic female subjects of varying aerobic fitness levels.

Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications.

Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of PVD across the spectrum of PH in LHD. Patients with PH-LHD [mean pulmonary artery (PA) pressure >20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg] and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD [combined post- and pre-capillary PH (CpcPH)] based upon pulmonary vascular resistance (PVR <3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV-PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O2 delivery, and peak O2 consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O2 tension, reduced alveolar ventilation, decreased pulmonary O2 diffusion, and greater ventilation-perfusion mismatch. Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV-PA uncoupling, ventricular interdependence, and impairment in O2 delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD.

Impaired exercise outcomes with significant bronchodilator responsiveness in children with prematurity-associated obstructive lung disease.

IntroductionPreterm‐born children have their normal in‐utero lung development interrupted, thus are at risk of short‐ and long‐term lung disease. Spirometry and exercise capacity impairments have been regularly reported in preterm‐born children especially those who developed chronic lung disease of prematurity (CLD) in infancy. However, specific phenotypes may be differentially associated with exercise capacity. We investigated exercise capacity associated with prematurity‐associated obstructive (POLD) or prematurity‐associated preserved ratio of impaired spirometry (pPRISm) when compared to preterm‐ and term‐controls with normal lung function.Materials and MethodsPreterm‐ and term‐born children identified through home screening underwent in‐depth lung function and cardiorespiratory exercise testing, including administration of postexercise bronchodilator, as part of the Respiratory Health Outcomes in Neonates (RHiNO) study.ResultsFrom 241 invited children, aged 7–12 years, 202 underwent exercise testing including 18 children with POLD (percent predicted (%)FEV1 and FEV1/FVC < LLN); 12 pPRISm (%FEV1 < LLN and FEV1/FVC ≥ LLN), 106 preterm‐controls (PTc, %FEV1 ≥ LLN) and 66 term‐controls (Tc, %FEV1 > 90%). POLD children had reduced relative workload, peak O2 uptake, CO2 production, and minute ventilation compared to Tc, and used a greater proportion of their breathing reserve compared to both control groups. pPRISm and PTc children also had lower O2 uptake compared to Tc. POLD children had the greatest response to postexercise bronchodilator, improving their %FEV1 by 19.4% (vs 6.3%, 6% 6.3% in pPRISm PTc,Tc, respectively; p < .001).ConclusionPreterm‐born children with obstructive airway disease had the greatest impairment in exercise capacity, and significantly greater response to postexercise bronchodilators. These classifications can be used to guide treatment in children with POLD.

Numerical study of singlet delta oxygen (O2(a1Δg)) generation and transport in the He/O2 atmospheric pressure plasma jet

This paper investigates the spatial-temporal evolution and the transport of the singlet delta oxygen (O2(a1Δg)) of an atmospheric pressure plasma jet using a 2D fluid modeling. The plasma jet is produced in pure helium or helium with small oxygen admixtures (no bigger than 2%), by applying a constant DC voltage of +5 kV on the annular electrode. It is found that, at the 0.7% O2 admixture, a higher O2(a1Δg) density is obtained inside the tube before the jet impacts the substrate. After the jet propagates along the substrate surface, the peak O2(a1Δg) density is transferred from the tube to the gap. Varying the O2 admixtures percentage in the working gas changes the O2(a1Δg) spatial distribution. The O2(a1Δg) with two thinner edges is dominantly produced in the helium–air mixing layer for pure helium. The addition of O2 in the working gas leads to O2(a1Δg) production in the tube. Meanwhile, the thickness of the O2(a1Δg) edges increases in the helium–air mixing layer. But the radius of the O2(a1Δg) density channel continuously reduces with the O2 admixture. The O2(a1Δg) density and its surface flux first increase within the 0.7% O2 admixture and then decreases with the further augment of the O2 admixture. The influence of the gas flow velocity on the production and transport of O2(a1Δg) is also studied. Increasing the gas flow velocity changes the spatial distribution of the O2(a1Δg) density from the solid structure to the annular structure in the gap. At the same time, lower volume average density and instantaneous flux are obtained at larger gas flow velocity.

Assessment of fusion pacing on exercise capacity in patients with cardiac resynchronisation therapy devices

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Local Departmental Research Funding Background Cardiac resynchronisation therapy (CRT) using fusion pacing requires correct timing of left ventricular pacing to right ventricular activation. The SyncAV™ algorithm, achieves this by dynamic reassessment of intrinsic atrio-ventricular (AV) conduction to adjust the paced/sensed AV delay. However, it is unclear whether AV optimisation maintains resynchronisation during exercise, or whether loss of fusion could lead to decreased exercise capacity. Cardio-pulmonary exercise testing (CPET) is the gold standard method for assessing exercise performance and can provide prognostic information in the heart failure population. Purpose We therefore used CPET measures of exercise capacity to compare the SyncAV™ algorithm to conventional pacing with fixed AV delays, in a double blinded, randomised crossover study (NCT03768804). Methods Patients at least 6 months post-CRT implant performed 2 CPET tests at least 1 week apart, with randomisation to either SyncAV™ with fusion pacing or conventional biventricular pacing with a fixed AVD of 120ms. All other programming was optimised to produce the narrowest QRS duration possible at rest in each case. Results Twenty patients (11 male, age 71 [65-77] years, median [interquartile range]) were recruited, with both ischaemic and non-ischaemic aetiology of heart failure. All had clinical and/or echocardiographic response to CRT. Optimised Fixed AVD and SyncAV™programming resulted in similar narrowing of QRS duration (QRSd) from intrinsic rhythm at rest (131 [103-137] vs 134 [110-137] ms for fixed AVD and SyncAV™ groups respectively, p=0.85). Overall, there was no difference in peak oxygen consumption (V̇O2peak) between programming (14.91 [12.61-18.16] vs 15.61 [12.18-19.70] ml/kg/min, p=0.19), or oxygen consumption at anaerobic threshold (VT1) (7.36 [6.93-8.94] vs 7.87 [6.77-9.24] ml/kg/min, p=0.42), or in the time to reach either V̇O2PEAK (p=0.81) or VT1 (p=0.39). The BORG rating of perceived effort was also similar between groups. CPET performance was also analysed comparing whichever programming gave the narrowest QRSd at rest (119 [96-136] vs 134 [119-142] ms, p&amp;lt;0.01). Eight were narrower with fixed AVD, 8 with SyncAV™ and in 4 there was no difference. QRSd during exercise (p=0.03), peak O2 pulse (ml/beat, a surrogate of stroke volume, p=0.03) and cardiac efficiency (watts/ml/kg/min, p=0.04) were significantly improved when programmed to the narrowest QRS duration at rest. Conclusion There is no significant difference in exercise capacity or QRSd between the use of optimised fixed AVD or SyncAV™, lending reassurance to fusion pacing being adequately maintained on exercise. In addition, programming with whichever algorithm gives the narrowest QRSd at rest is associated with a narrower QRSd during exercise, higher peak stroke volume and improved cardiac efficiency. This supports the use of SyncAV™ in the 40% of patients where this gave the narrowest QRSd at rest.

P295 EXERCISE OXYGEN KINETIC IN HYPERTROPHIC CARDIOMYOPATHY: RESULTS FROM A MULTICENTER CARDIOPULMONARY EXERCISE TESTING STUDY

Abstract Aims Reduced cardiac output (CO) has been considered crucial in symptoms’ genesis in hypertrophic cardiomyopathy (HCM). We evaluated the cardiopulmonary exercise testing (CPET) response in HCM focusing on parameters strongly associated with stroke volume (SV) and cardiac output (CO), such as oxygen uptake (VO2) and O2–pulse, considering both their absolute values and temporal behavior during physical exercise. Methods and Results We enrolled 312 non–end stage HCM patients, divided according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva maneuver (72% with LVOTO&amp;lt;30; 10% between 30 and 49 and 18% ≥ 50mmHg). Peak VO2 (percent of predicted), O2–pulse and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety–six (31%) HCM patients presented an abnormal O2–pulse temporal behavior, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106±45 vs. 130±49W), VO2 (74±17 vs. 80±20%) and O2–pulse (12 [9–14] vs. 14 [11–17]ml/beat), with higher VE/VCO2 slope (28 [25–31] vs. 27 [24–31]) (p &amp;lt; 0.005 for all). Only 2 patients had an abnormal VO2/work slope. Conclusion None of CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal O2–pulse exercise behavior, which is strongly related to inadequate SV during exercise, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, helping identifying more advanced disease irrespectively of LVOTO. Adding O2–pulse kinetics evaluation to standard CPET could lead to a potential incremental benefit in terms of HCM prognostic stratification and, then, therapeutic management.

QRS fragmentation and prolongation as predictors of exercise capacity in patients after Fontan palliation.

Patients with Fontan anatomy are at increased risk for exercise intolerance and early morbidity and mortality. QRS complex fragmentation (fQRS) and prolongation have been studied in multiple heart diseases, but their clinical importance is unknown in the Fontan population. A retrospective cross-sectional study was performed. ECGs were evaluated for QRS prolongation (>98 percentile for age) and fQRS (≥3 R-waves/notches in the R/S complex [more than two in RBBB] in ≥2 contiguous leads). The primary outcome measures were CPET performance. Total 90 patients (median age 18 years, 57% male, 59% RV dominant) were included; 13% had fQRS and 31% had prolonged QRS. Demographically, patients with fQRS or prolonged QRS were like those without. Peak VO2 (64% vs. 63%, p .45), VE/VCO2 slope (85% vs. 88%, p = .74), and O2 pulse (149% vs. 129%, p = .83) were similar in the fQRS group versus those without. Upon multi-variable regression, body mass index (β = -0.38, p < .01) and QRS duration (β = -0.29, p < .01) were independently associated with % predicted VO2; fQRS was not. Lower cardiac index (2.2 vs. 2.8 L/min/m2 , p = .03) and higher ventricular end-diastolic pressure (13 vs. 10 mmHg, p = .02) was seen with fQRS. QRS fragmentation is present in patients with Fontan physiology. fQRS showed no association with CPET performance but was related to invasive hemodynamic markers of ventricular performance. QRS duration may be a better predictor of exercise function following Fontan.

Reactivity of flavonoids toward superoxide radical: An electrochemical approach

The reactivities of a set of 18 diverse flavonoids against electrochemically generated superoxide anion radical were studied by monitoring changes in O2/O2·− cyclic voltammetry response upon addition of increasing concentrations of flavonoids. In the presence of flavonoids, the O2·- anodic peak current decreased, while the cathodic peak of O2 remained almost unchanged. Concomitantly with an O2·- anodic peak current decrease, a new irreversible cathodic pre-peak before the O2 reduction peak appeared on the CVs of O2/O2·− upon adding flavonoids. This phenomenon is described in detail for the first time on the basis of experimental measurements and model calculations. Based on the changes in O2/O2·− cyclic voltammetry response upon adding flavonoids, we could draw conclusions about the mechanism of superoxide radical scavenging by flavonoids. The superoxide radical scavenging activities of flavonoids, determined by measuring the anodic current decay of the radical in the presence of increasing concentrations of flavonoids, were expressed in terms of EC60 values, i.e. the concentration of flavonoid needed to consume 40% of a superoxide radical. All of the studied flavonoids showed a more or less pronounced superoxide radical scavenging activity, depending on their structural features. The structure-activity relationship was discussed. Superoxide radical scavenging activities of flavonoids correlated well with their electrochemical oxidation potentials, implying that the scavenging activity of flavonoids is mainly governed by their redox properties.

Assessment of Cardiac Contribution to Exercise Intolerance in Pediatric Bilateral Lung Transplant Recipients

<h3>Purpose</h3> Exercise intolerance is common among lung transplant (LTx) recipients. However, there is limited data in pediatrics. Since the heart and lungs work in concert with each other, we aim to assess the cardiac contribution to exercise intolerance in pediatric LTx recipients by examining the prevalence of traditional cardiac risk factors (CRFs) and their performance on cardiopulmonary exercise testing (CPET). <h3>Methods</h3> All pediatric LTx recipients followed at a single center who had a resting echocardiogram (echo), were able to exercise, and had a routine CPET in the last 2 years were included. CRFs including hypertension, hyperlipidemia, diabetes mellitus (DM), body mass index (BMI), activity level, and smoking history were assessed. CPET-derived maximal oxygen consumption (VO2_max) and % predicted peak VO2 (ppVO2_max) were used to assess exercise tolerance. Left ventricular (LV) systolic and diastolic function were also assessed on resting echo. <h3>Results</h3> 11 bilateral LTx patients (7M, 4F, and median age 21 years, range 17-28 years) formed the cohort. Median time since LTx is 6 years, range 2-10 years. The majority of patients (8, 73%) had multiple CRFs: 7 (64%) had hypertension, 7 (64%) hyperlipidemia, 6 (55%) DM, 2 with BMI ≥25 kg/m², and 6 (55%) sedentary lifestyle. None had a smoking history. On resting echo, all had normal LV systolic function. 5 (45%) had LV diastolic dysfunction. On CPET, 9 (82%) had abnormal ppVO2_max ≤85%, even with maximal patient effort. None had ischemia. Surprisingly, only 2 of the 9 had a pulmonary limitation to exercise with abnormal breathing reserve (<25%) to account for abnormal ppVO2_max. 6 had a cardiac limitation to exercise attributed to inability to augment stroke volume (decreased % predicted peak O2 pulse). 1 had an abnormal respiratory exchange ratio (RER <1.10), with a normal % predicted peak O2 pulse and a chronotropic deficit (achieving 60% predicted peak heart rate). Of note, 2 patients had normal exercise tolerance with ppVO2_max >85%. <h3>Conclusion</h3> Despite maximal effort, low exercise tolerance is common among pediatric LTx recipients. The high prevalence of CRFs, diastolic dysfunction, and inability to augment stroke volume suggest a potential cardiac contribution to exercise intolerance for this cohort. Further studies are needed to define potential cardiac issues in exercise tolerance in pediatric LTx recipients.

Differences in Cardiac Output and Aerobic Capacity Between Sexes Are Explained by Blood Volume and Oxygen Carrying Capacity.

Whether average sex differences in cardiorespiratory fitness can be mainly explained by blood inequalities in the healthy circulatory system remains unresolved. This study evaluated the contribution of blood volume (BV) and oxygen (O2) carrying capacity to the sex gap in cardiac and aerobic capacities in healthy young individuals. Healthy young women and men (n = 28, age range = 20–43 years) were matched by age and physical activity. Echocardiography, blood pressures, and O2 uptake were measured during incremental exercise. Left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q), peak O2 uptake (VO2peak), and BV were assessed with precise methods. The test was repeated in men after blood withdrawal and reduction of O2 carrying capacity, reaching women’s levels. Before blood normalization, exercise cardiac volumes and output (LVEDV, SV, Q) adjusted by body size and VO2peak (42 ± 9 vs. 50 ± 11 ml⋅min–1⋅kg–1, P < 0.05) were lower in women relative to men. Blood normalization abolished sex differences in cardiac volumes and output during exercise (P ≥ 0.100). Likewise, VO2peak was similar between women and men after blood normalization (42 ± 9 vs. 40 ± 8 ml⋅min–1⋅kg–1, P = 0.416). In conclusion, sex differences in cardiac output and aerobic capacity are not present in experimental conditions matching BV and O2 carrying capacity between healthy young women and men.

Effect of a 3-Year Lifestyle Intervention in Patients with Chronic Kidney Disease: A Randomized Clinical Trial.

Supervised lifestyle interventions have the potential to significantly improve physical activity and fitness in patients with CKD. To assess the efficacy of a lifestyle intervention in patients with CKD to improve cardiorespiratory fitness and exercise capacity over 36 months, we conducted a randomized clinical trial, enrolling 160 patients with stage 3-4 CKD, with 81 randomized to usual care and 79 to a 3-year lifestyle intervention. The lifestyle intervention comprised care from a multidisciplinary team, including a nephrologist, nurse practitioner, exercise physiologist, dietitian, diabetes educator, psychologist, and social worker. The exercise training component consisted of an 8-week individualized and supervised gym-based exercise intervention followed by 34 months of a predominantly home-based program. Self-reported physical activity (metabolic equivalent of tasks [METs] minutes per week), cardiorespiratory fitness (peak O2 consumption [VO2peak]), exercise capacity (maximum METs and 6-minute walk distance) and neuromuscular fitness (grip strength and get-up-and-go test time) were evaluated at 12, 24, and 36 months. The intervention increased the percentage of patients meeting physical activity guideline targets of 500 MET min/wk from 29% at baseline to 63% at 3 years. At 12 months, both VO2peak and METs increased significantly in the lifestyle intervention group by 9.7% and 30%, respectively, without change in the usual care group. Thereafter, VO2peak declined to near baseline levels, whereas METs remained elevated in the lifestyle intervention group at 24 and 36 months. After 3 years, the intervention had increased the 6-minute walk distance and blunted declines in the get-up-and-go test time. A 3-year lifestyle intervention doubled the percentage of CKD patients meeting physical activity guidelines, improved exercise capacity, and ameliorated losses in neuromuscular and cardiorespiratory fitness.

Assessment of Exercise Function in Children and Young Adults with Hypertrophic Cardiomyopathy and Correlation with Transthoracic Echocardiographic Parameters.

Exercise function is well characterized in adults with hypertrophic cardiomyopathy (HCM); however, there is a paucity of data in children and young adults with HCM. Here we sought tocharacterize exercise function in young people with HCM, understand limitations in exercise function by correlating exercise function parameters with echocardiogram parameters and identify prognostic value of exercise parameters. We performed aretrospective, single-center cohort study characterizing exercise function in patients < 26years old with HCM undergoing cardiopulmonary exercise testing (CPET). Patients with syndromic HCM or submaximal effort were excluded. We compared exercise function in this cohort to population normal values and measured changes in exercise function over time. We correlated exercise function parameters with echocardiographic parameters and investigated the relationship between exercise test parameters and a clinical composite outcome comprised of significant ventricular arrhythmia, death, or heart transplantation. We identified 229 CPETs performed by 117 patients (mean age at time of first CPET 15.6 ± 3.2years). Mean %-predicted peak VO2, O2 pulse, and peak heart rate were statistically significantly depressed compared to population normal values and exercise function gradually worsened over time. Abnormal exercise testing correlated closely with echocardiographic indices of diastolic dysfunction. There was a trend toward increased incidence of poor clinical outcome in patients with abnormal exercise function.While adverse clinical outcomes were rare, normal exercise function appears to be a marker of low risk for adverse clinical outcomes in this population.

Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level.

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95%CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies.

Sex and age interaction in fundamental circulatory volumetric variables at peak working capacity

BackgroundWhether the fundamental hematological and cardiac variables determining cardiorespiratory fitness and their intrinsic relationships are modulated by major constitutional factors, such as sex and age remains unresolved.MethodsTransthoracic echocardiography, central hemodynamics and pulmonary oxygen (O2) uptake were assessed in controlled conditions during submaximal and peak exercise (cycle ergometry) in 85 healthy young (20–44 year) and older (50–77) women and men matched by age-status and moderate-to-vigorous physical activity (MVPA) levels. Main outcomes such as peak left ventricular end-diastolic volume (LVEDVpeak), stroke volume (SVpeak), cardiac output (Qpeak) and O2 uptake (VO2peak), as well as blood volume (BV), BV–LVEDVpeak and LVEDVpeak–SVpeak relationships were determined with established methods.ResultsAll individuals were non-smokers and non-obese, and MVPA levels were similar between sex and age groups (P ≥ 0.140). BV per kg of body weight did not differ between sexes (P ≥ 0.118), but was reduced with older age in men (P = 0.018). Key cardiac parameters normalized by body size (LVEDVpeak, SVpeak, Qpeak) were decreased in women compared with men irrespective of age (P ≤ 0.046). Older age per se curtailed Qpeak (P ≤ 0.022) due to lower heart rate (P < 0.001). In parallel, VO2peak was reduced with older age in both sexes (P < 0.001). The analysis of fundamental circulatory relationships revealed that older women require a higher BV for a given LVEDVpeak than older men (P = 0.024).ConclusionsSex and age interact on the crucial circulatory relationship between total circulating BV and peak cardiac filling, with older women necessitating more BV to fill the exercising heart than age- and physical activity-matched men.