Arteriovenous Oxygen Difference Research Articles

Sex Differences in Cardiovascular Adaptations Following Aerobic Exercise Training Programs: A Systematic Review and Meta-analysis.

The influence of aerobic exercise training on cardiovascular adaptations in healthy males vs females is unclear. This systematic review and meta-analysis summarized sex-based differences in cardiac adaptations following aerobic exercise training interventions in healthy adults. Five electronic databases were searched from inception to June 2024. Cardiac adaptation data included peak oxygen uptake, heart rate, arteriovenous oxygen difference, systolic and diastolic blood pressure, stroke volume, cardiac output, left ventricular (LV) mass, LV end diastolic volume (LVEDV), LV end systolic volume (LVESV), and LV ejection fraction (LVEF). Meta-analyses were conducted in RevMan 5.4. Meta-analyses were conducted on 4 outcomes: LV mass, LVEDV, LVESV, and LVEF. The meta-analysis revealed no sex differences in LV mass (standardized mean difference= -0.01, 95% confidence interval [CI]: -0.29, 0.27, P= 0.97), LVESV (mean difference [MD]= 1.85, 95% CI: -3.45, 7.10, P= 0.5), or LVEF (MD= -0.9, 95% CI: -3.26, 1.46, P= 0.45) following aerobic exercise interventions. Meta-analyses revealed a sex difference in LVEDV: males show a greater improvement in LVEDV (MD= 7.67, 95% CI: 2.75, 12.59, P= 0.002) than females after aerobic exercise training. No other sex differences were observed in any of the other outcomes. The overall risk of bias was low, and the quality of evidence was moderate. Aerobic exercise interventions were associated with a larger increase in LVEDV in men relative to women, yet no sex differences were found in cardiac morphology (LV mass) or functional indices (LVEF).

Abstract 4139170: Relationship between hemodynamics and oxygen consumption in hypertrophic cardiomyopathy during maximal stress testing

Background: Hypertrophic cardiomyopathy (HCM) is a global heart disease with great variability in disease severity, which can lead to significant impairment of exercise capacity. In healthy populations, oxygen consumption is related to cardiac output and arteriovenous oxygen difference. We sought to determine the relationship between hemodynamics (cardiac output and stroke volume) and oxygen consumption in HCM compared to healthy controls during maximal stress testing. Aims: To evaluate associations between the trajectories of hemodynamic function and oxygen consumption in HCM compared to healthy controls. Methods: Twenty individuals with HCM (51±15 years old, body mass index (BMI): 28±3 kg/m 2 , females, n=4) and 16 healthy controls (66±7 years old, 27±6 kg/m 2 , females, n=6) were included in the present study. Participants completed a maximal-graded stress test coupled with non-invasive hemodynamic bioreactance (cardiac output, stroke volume) and gas exchange (oxygen consumption, VO 2 ) measurements. Data were analyzed in quartiles (exercise only) and phases (rest, pre-pedalling, exercise and recovery) of the maximal-graded stress test. Results: In HCM, cardiac output declined in the fourth quartile of the exercise phase of the stress test (-0.39 L/min, p <0.001) whilst VO 2 increased (3.86 ml/kg/min, p <0.001). There was a significant difference in the gradient of cardiac output between HCM and controls in the final quartile of the test (-1.6 vs. 18.1 L/min, p<0.001). In coherence, stroke volume declined in the fourth quartile of the test (-18.4 ml, p <0.01) in response to increasing VO 2 in HCM. The rates of recovery were faster in HCM compared to the control group for VO 2 (-4.3 vs -2.6 mL/second, p<0.001), cardiac output (-0.03 vs -0.02 L/second, p<0.001), heart rate (-0.17 vs -0.10 beats/second, p<0.001), and stroke volume (-0.18 vs -0.07 L/second, p<0.001). Conclusions: In HCM, cardiac output declined during the later stages of maximal stress testing whereas in controls it continued to rise, indicating impaired maximal cardiac output responses to exercise. These findings have implications for exercise prescription and training regimens in HCM suggesting avoidance of maximal exercise levels.

Abstract 4143256: Non-invasive, Radiation-free, Non-contrast Myocardial Volume Oxygen Consumption Quantification Using Free-breathing MR Blood Oximetry

Background: Myocardial oxygen consumption (MVO 2 ) is a central marker in measuring cardiac energetics. Current methods to quantify MVO 2 are inaccessible due to the requirement of invasive procedures or PET agents that require onsite cyclotrons. Hypothesis A free-breathing, non-ECG-gated, motion-resolved Cardiac MR blood oximetry technique can noninvasively quantify MVO 2 in standard clinical MRI scanners without using ionizing radiation and contrast agents. Method: The developed free-breathing CMR imaging technique was prescribed in a 3T clinical scanner to the mid left ventricle (LV) and the cross-section of the coronary sinus(CS) slices of the heart to obtain the corresponding blood oxygenation (SbO 2 ) and the hematocrit (Hct) in heart chambers. 2D phase contrast CMR was performed in the CS to quantify the myocardial blood flow (MBF). The MVO 2 was quantified with Fick’s law (MVO 2 =arterio-venous oxygen difference x MBF). We examined the developed method in healthy pigs (N=7) under rest and adenosine stress and validated it against invasive blood sampling. In addition, we tested the method’s clinical feasibility in healthy human volunteers (N=4). Results: Comparable blood oxygenation levels (SbO 2 ) and MVO 2 were measured and compared between the non-invasive CMR and invasive ground truth (Fig. 1). Significantly increased coronary sinus SbO 2 is observed in both methods during adenosine infusion. It is accompanied by decreased MVO 2 and rate pressure product (RPP) (Rest: CMR=10.2±2.7ml/min, Inv.=10.8±6.9 ml/min, RPP=7956.9±620.9 mmHg/min; Stress: CMR=5.3±1.9 ml/min, Inv=6.3±3.6 ml/min, RPP=5338.2±618.3 mmHg/min). In Fig. 2, the healthy human volunteers' MVO 2 estimations(14.1±6.7ml/min) shows no statistical difference compared to the previous invasive measurements(16.5±4.8 ml/min, Ganz, et al. circulation 1971). Conclusions: The proposed noninvasive CMR technique can quantify MVO 2 in standard MRI scanners without using a needle. It has the potential to provide an accessible, risk-free assessment of myocardial metabolism for patients with potential metabolism impairments.

Oxygen Delivery and Consumption in Patients Who Are Comatose After Out-of-Hospital Cardiac Arrest Are Affected by Blood Pressure Target.

In the management of patients resuscitated from out-of-hospital cardiac arrest, a primary goal is to restore sufficient oxygen delivery (DO2) to meet demands in oxygen consumption (VO2). This post hoc analysis of the BOX (Blood Pressure and Oxygen Targets) study included adult patients who were comatose and experienced out-of-hospital cardiac arrest from a presumed cardiac cause, who were randomized to a mean arterial blood pressure (MAP) target of 63 mm Hg (MAP63) or 77 mm Hg (MAP77) and a Restrictive PaO2 target of 9 to 10 kPa versus a Liberal target of 13 to 14 kPa in a 2×2 factorial design. A pulmonary artery catheter was inserted following randomization. DO2 and VO2 were calculated as: DO2=cardiac output × arterial oxygen content, and VO2= cardiac output × arteriovenous oxygen difference. Of 789 patients, 730 (92.5%) were included in this substudy. A total of 362 patients were randomized to MAP77, and 368 to MAP63, 368 to a liberal Pao2 target, and 362 to a restrictive target. At all prespecified time points, DO2 in MAP77 was higher compared with MAP63, with a cumulative treatment effect of 203 L (95% CI, 132-274) O2 after 36 hours. VO2 was higher in MAP77 after 36 hours, with a cumulative treatment effect of 21.9 L (95% CI, 5.8-38) O2, compared with the MAP63 group. Targeting a MAP of 77 mm Hg resulted in an overall increase in DO2 and a smaller increase in VO2 compared with a MAP target of 63 mm Hg. A higher Pao2 target did not result in any difference in DO2 or VO2.

Longitudinal decline in peak V̇o2 with aging in a healthy population is associated with a reduction in peripheral oxygen utilization but not in cardiac output.

Aging is associated with a significant decline in aerobic capacity assessed by maximal exercise oxygen consumption (V̇o2max). The relative contributions of the specific V̇o2 components driving this decline, namely cardiac output (CO) and arteriovenous oxygen difference (A - V)O2, remain unclear. We examined this issue by analyzing data from 99 community-dwelling participants (baseline age: 21-96 yr old; average follow-up: 12.6 yr old) from the Baltimore Longitudinal Study of Aging, free of clinical cardiovascular disease. V̇o2peak, a surrogate of V̇o2max, was used to assess aerobic capacity during upright cycle ergometry. Peak exercise left ventricular volumes, heart rate, and CO were estimated using repeated gated cardiac blood pool scans. The Fick equation was used to calculate (A - V)O2diff,peak from COpeak and V̇o2peak. In unadjusted models, V̇o2peak, (A - V)O2diff,peak, and COpeak declined longitudinally over time at steady rates with advancing age. In multiple linear regression models adjusting for baseline values and peak workload, however, steeper declines in V̇o2peak and (A - V)O2diff,peak were observed with advanced entry age but not in COpeak. The association between the declines in V̇o2peak and (A - V)O2diff,peak was stronger among those ≥50 yr old compared with their younger counterparts, but the difference between the two age groups did not reach statistical significance. These findings suggest that age-associated impairment of peripheral oxygen utilization during maximal exercise poses a stronger limitation on peak V̇o2 than that of CO. Future studies examining interventions targeting the structure and function of peripheral muscles and their vasculature to mitigate age-associated declines in (A - V)O2diff are warranted.NEW & NOTEWORTHY The age-associated decline in aerobic exercise performance over an average of 13 yr in community-dwelling healthy individuals is more closely associated with decreased peripheral oxygen utilization rather than decreased cardiac output. This association was more evident in older than younger individuals. These findings suggest that future studies with larger samples examine whether these associations vary across the age range and whether the decline in cardiac output plays a greater role earlier in life. In addition, studies focused on determinants of peripheral oxygen uptake by exercising muscle may guide the selection of preventive strategies designed to maintain physical fitness with advancing age.

Effects of exercise training on cardiac output in subjects with heart failure with preserved ejection fraction (HFpEF) — a protocol for a systematic review and meta-analysis

BackgroundPatients with heart failure with preserved ejection fraction (HFpEF) commonly experience exercise intolerance, resulting in reduced cardiorespiratory fitness. This is characterised by a decreased maximal oxygen uptake (V̇O2peak), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO2). While exercise training has been shown to improve V̇O2peak in HFpEF patients, the effects on CO remain unclear. The aim of this study is to systematically review and analyse the current evidence on the effects of supervised exercise training on CO in patients with HFpEF.MethodsWe will systematically search for literature describing the effects of supervised exercise training on CO in patients with HFpEF. All eligible studies published before 30 June 2023 in the following electronic databases will be included: MEDLINE (Ovid), Embase (Ovid), SPORTDiscus (EBSCOhost), and CENTRAL (Cochrane Library). Effect sizes will be extracted for CO before and after a supervised exercise training intervention at rest and maximal exercise. Mass of heterogeneity (I2) will be calculated, and either fixed-effect models or random-effect models will be used for meta-analysis. To detect a potential publication bias, funnel plot analyses will be performed.DiscussionWhile several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O2peak, CO, and a-vDO2 are much scarcer, especially in patients with HFpEF. From a physiological perspective, measuring CO before and after supervised exercise training seems to be a reasonable way to accurately operationalise a potential improvement in cardiac function.Systematic review registrationPROSPERO CRD42022361485.

Changes in the indicators of hemodynamics and oxygen transport in patients with idiopathic pulmonary arterial hypertension depending on their survival

Background. Idiopathic pulmonary arterial hypertension (IPAH) is a severe disease that affects the vessels of the pulmonary circulation and leads to right ventricular failure and death of patients. Indicators of hemodynamics and oxygen transport play central role in the progression and development of the disease. Objective: to evaluate indicators of hemodynamics, oxygen transport. Materials and methods. The study included 124 patients with IPAH. They were divided into two groups: alive patients (group 1) and those who died (group 2). All of them underwent general clinical examinations, a 6-minute walk test, transthoracic and speckle tracking echocardiography, right heart catheterization, blood gas analysis and calculation of hemodynamic parameters. Results. We calculated and compared the right (RVSWI) (19.93 ± 7.84 vs. 16.47 ± 4.67 g·m·m–2, p = 0.009) and left ventricular stroke work index (LVSWI) (39.47 ± 10.53 vs. 35.92 ± 11.19 g·m·m–2, p = 0.036) and their ratio (RVSWI/LVSWI) (0.59 ± 0.16 vs. 0.46 ± ± 0.13, p = 0.008), right (RVPC) (97.00 ± 2.16 vs. 1.82 ± 1.04 g·m, p = 0.001) and left ventricular pump coefficient (LVPC) (5.36 ± 4.84 vs. 4.41 ± 2.15 g·m, p = 0.04) and their ratio (RVPC/LVPC) (0.54 ± 0.19 vs. 0.44 ± 0.11, p = 0.05) in both groups of patients. Also, we found differences in partial pressure of carbon dioxide (PaCO2) of venous blood (34.5 ± 5.1 vs. 40.2 ± 6.9 mm Hg, p = 0.02), partial pressure of oxygen (PaO2) of arterial blood (90.2 ± 15.1 vs. 78.9 ± 11.2 mm Hg; p = 0.01), arteriovenous oxygen difference (A-vO2) (4.5 ± 1.2 vs. 5.0 ± 0.8 ml/dL, p = 0.02) between both groups. Conclusions. RVSWI, LVSWI, RVSWI/LVSWI, RVPC, LVPC, RVPC/LVPC were significantly different between the groups. The use of the above hemodynamic parameters can help in a deeper understanding of the prognosis in IPAH patients. Performance of oxygen transport indicators (PaCO2, PaO2) and A-vO2 in IPAH patients provides a broader understanding of the status and prognosis of this disease.

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.

EFFECT OF RESISTANCE TRAINING THROUGH IN-PERSON AND TELECONFERENCING SESSIONS IN REHABILITATION OF ACUTE STROKE PATIENTS.

To determine whether application of a strength training regimen yields measurable results on stroke survivors and compare different methods for the proposed intervention. Ninety stroke patients were recruited from the neurological clinic of a local third-level clinic. Sixty patients participated in a strength training regimen with trainings taking place 3 times a week for 12 weeks with the use of resistance bands. Thirty of these patients were given face-to-face sessions and 30 patients were given trainings through an on-line platform. The last 30 patients who comprised the control group only followed usual care after the stroke. The applied strength regimen had a statistically significant effect on Visual Analog Scale scores of stroke patients who received it (p = 0.009), as well as in the teleconferencing group (p = 0.004). The measured arteriovenous oxygen difference was elevated for stroke patients who received the intervention as a whole (p = 0.007). Patients who were trained in person and the ones who were trained via teleconferencing yielded similar results as evaluated through the VAS index. Administration of strength training 3 times weekly for 12 weeks to stroke patients yielded measurable results in terms of general function and quality of life.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and limit of tolerance during progressive forearm exercise in men: a randomized crossover trial.

Beetroot juice (BRJ) supplementation increases nitric oxide bioavailability with hypoxia and acidosis, characteristics of high-intensity exercise. We investigated whether BRJ improved forearm oxygen delivery:demand matching in an intensity-dependent manner. Healthy men (21±2.5 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON, Canada). Participants completed a forearm incremental exercise test to limit of tolerance (IET-LOT) 2.5 h post placebo (PL) versus BRJ (2 completed PL/BRJ vs. 9 completed BRJ/PL) within a 2-week period. Data are presented as mean±standard deviation. There was a significant main effect of drink (PL<BRJ; P=0.042, ηp2=0.385) and drink × intensity interaction for arteriovenous oxygen difference (PL<BRJ; P=0.03; ηp2= 0.197; 20%-50% and 90% LOT). BRJ did not influence oxygen delivery (P=0.893, ηp2=0.002), forearm blood flow (P=0.589, ηp2=0.03) (forearm vascular conductance (P=0.262, ηp2=0.124), mean arterial pressure (P=0.254,ηp2=0.128)), oxygen consumption (P=0.194, ηp2=0.179) or LOT (P=0.432, d=0.247). In healthy men, BRJ did not improve forearm oxygen delivery (vasodilatory or pressor response) during IET-LOT. Increased arteriovenous oxygen difference at submaximal intensities did not significantly influence oxygen consumption or performance across the entire range of forearm exercise intensities. This study adds to the growing body of evidence that BRJ does not influence small muscle mass blood flow in humans regardless of exercise intensity.

Biological sex does not influence the peak cardiac output response to twelve weeks of sprint interval training

Sprint interval training (SIT) increases peak oxygen uptake (V̇O2peak) but the mechanistic basis is unclear. We have reported that 12 wk of SIT increased V̇O2peak and peak cardiac output (Q̇peak) and the changes in these variables were correlated. An exploratory analysis suggested that Q̇peak increased in males but not females. The present study incorporated best practices to examine the potential influence of biological sex on the Q̇peak response to SIT. Male and female participants (n = 10 each; 21 ± 4 y) performed 33 ± 2 sessions of SIT over 12 wk. Each 10-min session involved 3 × 20-s ‘all-out’ sprints on an ergometer. V̇O2peak increased after SIT (3.16 ± 1.0 vs. 2.89 ± 1.0 L/min, η2p = 0.53, p < 0.001) with no sex × time interaction (p = 0.61). Q̇peak was unchanged after training (15.2 ± 3.3 vs. 15.1 ± 3.0 L/min, p = 0.85), in contrast to our previous study. The peak estimated arteriovenous oxygen difference increased after training (204 ± 30 vs. 187 ± 36 ml/L, p = 0.006). There was no effect of training or sex on measures of endothelial function. We conclude that 12 wk of SIT increases V̇O2peak but the mechanistic basis remains unclear. The capacity of inert gas rebreathing to assess changes in Q̇peak may be limited and invasive studies that use more direct measures are needed.

Attenuated peripheral oxygen extraction and greater cardiac output in women with posttraumatic stress disorder during exercise.

Posttraumatic stress disorder (PTSD) is associated with an increased risk of developing cardiovascular disease, especially in women. Evidence indicates that men with PTSD exhibit lower maximal oxygen uptake (V̇o2max) relative to controls; however, whether V̇o2max is blunted in women with PTSD remains unknown. Furthermore, it is unclear what determinants (i.e., central and/or peripheral) of V̇o2max are impacted by PTSD. Therefore, we evaluated the central (i.e., cardiac output; Q̇c) and peripheral (i.e., arteriovenous oxygen difference) determinants of V̇o2max in women with PTSD; hypothesizing that V̇o2max would be lower in women with PTSD compared with women without PTSD (controls), primarily due to smaller increases in stroke volume (SV), and therefore Q̇c. Oxygen uptake (V̇o2), heart rate (HR), Q̇c, SV, and arteriovenous oxygen difference were measured in women with PTSD (n = 14; mean [SD]: 43 [11] yr,) and controls (n = 17; 45 [11] yr) at rest, and during an incremental maximal treadmill exercise test, and the Q̇c/V̇o2 slope was calculated. V̇o2max was not different between women with and without PTSD (24.3 [5.6] vs. 26.4 [5.0] mL/kg/min; P = 0.265). However, women with PTSD had higher Q̇c [P = 0.002; primarily due to greater SV (P = 0.069), not HR (P = 0.285)], and lower arteriovenous oxygen difference (P = 0.002) throughout exercise compared with controls. Furthermore, the Q̇c/V̇o2 slope was steeper in women with PTSD relative to controls (6.6 [1.4] vs. 5.7 [1.0] AU; P = 0.033). Following maximal exercise, women with PTSD exhibited slower HR recovery than controls (P = 0.046). Thus, despite attenuated peripheral oxygen extraction, V̇o2max is not reduced in women with PTSD, likely due to larger increases in Q̇c.NEW & NOTEWORTHY The current study indicates that V̇o2max is not different between women with and without PTSD; however, women with PTSD exhibit blunted peripheral extraction of oxygen, thus requiring an increase in Q̇c to meet metabolic demand during exercise. Furthermore, following exercise, women with PTSD demonstrate impaired autonomic cardiovascular control relative to sedentary controls. We interpret these data to indicate that women with PTSD demonstrate aberrant cardiovascular responses during and immediately following fatiguing exercise.

Mechanisms of adaptation to high intensity exercise in hypertrophic cardiomyopathy

Abstract Background Many individuals with hypertrophic cardiomyopathy (HCM) demonstrate exercise limitation. For a proportion this may be related to their overall cardiorespiratory fitness influenced by physical activity habits, body mechanics, or habitus. In others there is evidence of central and/or peripheral pathophysiology. However, some individuals with HCM demonstrate favourable adaptation to exercise. In the SAFE-HCM study, participants who underwent 12 weeks of high intensity exercise showed significant improvement in exercise indices including peak VO2, VO2/kg at anaerobic threshold (AT), time to AT, and overall exercise time compared to a usual care group. Purpose There have been no studies investigating the mechanistic adaptation(s) to exercise in HCM. This sub-study aimed to identify whether the observed improvements in exercise indices were attributable to central or peripheral adaptation. Methods Eighty patients with HCM (45.7±8.6 years) underwent baseline clinical, quality of life and psychological assessment. Individuals were randomised to a 12-week high intensity exercise programme (n=40) or usual care (n=40). Baseline evaluation was repeated at 12 weeks. The Fick equation (oxygen uptake (VO2) = cardiac output (CO) X (arterial-venous oxygen content (a-vO2 difference)) was used to assess whether central and/or peripheral adaptation was responsible for observed improvements. 2D speckle tracking imaging was utilised to calculate left ventricular longitudinal strain from the apical 2-, 3- and 4 chamber views (EchoPAC, V202, GE Healthcare). Results 12-weeks of high intensity exercise training produced a statistically significant increase in CO (1.1±0.4 L/min, CI (0.2,2.0), p=0.016) compared with the usual care group. There was no difference in the change in a-vO2 difference between groups (p=0.682) suggesting central adaptation to high intensity exercise. This was driven by an increase in stroke volume (SV) (6.1±3.0ml, CI (0.1,12.2), p=0.047) rather than an increase in heart rate (0.6±3.6 bpm, CI (-6.6,7.7), p=0.874). However, there was no change in resting myocardial deformation to account for the observed improvement in CO. Analysis of strain data demonstrated no difference in resting regional 4Ch (-0.7±0.6, CI (-1.9, 0.5), p=0.270) 3Ch (-1.1±0.9, CI (-2.8, 0.6), p=0.201), 2Ch (-1.3±0.9, CI (-3.1, 0.5), p=0.162) or average global longitudinal strain (0.9±0.6, CI (-2.2,0.3), p=0.144) between groups at 12 weeks. Conclusion Favourable central adaptations, predominantly driven by an increase in SV, enable improvements in exercise capacity following a high intensity exercise programme. Further studies are required to understand the physiological processes underlying this adaptation including assessment of myocardial deformation at peak exercise

Exercise training affects hemodynamics and exercise capacity in cases of heart failure with preserved ejection fraction: a non-randomized controlled trial in individuals aged 65-80 years.

Exercise training is an established intervention method for improving exercise capacity and survival rates in patients with heart failure with preserved ejection fraction (HFpEF). However, most reports have focused on European and American patients, with limited data regarding the effects of exercise training on cardiac function, hemodynamics, and exercise capacity in East Asian patients. This study investigated the effects of exercise training on cardiac function, hemodynamics, and exercise capacity in Japanese patients aged 65-80 years with HFpEF. This single-center, open-label, non-randomized, controlled trial prospectively enrolled 99 outpatients. Eligibility criteria for HFpEF patients were an HFA score ≥5 in addition to clinical symptoms of heart failure and left ventricular diastolic dysfunction. Exercise training in the intervention group consisted of aerobic exercise and strength training thrice weekly for 5 months. Patients in the control group continued the usual treatment for 5 months. Resting cardiac function was evaluated using echocardiography. Peak oxygen uptake (peakVO2), ventilatory equivalent (VE) vs. carbon dioxide output (VCO2) slope, peak cardiac output index, and arteriovenous oxygen difference were calculated using cardiopulmonary exercise testing combined with impedance cardiography. After 5 months of exercise training, remarkable interactions were observed, with peakVO2 as the primary outcome. Additionally, significant interactions were observed between hemodynamic indices and some echocardiographic parameters. The mean percentage change in peakVO2 from baseline was 8.3% in the intervention group. Fifteen study participants (30.1%) in the intervention group achieved a clinically meaningful change of 3.0 ml/min/kg (10% improvement) in peakVO2 from baseline. The group with 3.0 ml/min/kg or 10% improvement in peakVO2 from baseline had a considerably lower prevalence of diabetes mellitus and VE vs. VCO2 slope and considerably higher left atrial-global longitudinal strain values than the group without any notable improvements. Although exercise training can help improve exercise intolerance in Japanese patients aged 65-80 years with HFpEF, its benefits are limited. Our results suggest that HFpEF, complicated by diabetes mellitus and decreased ventilatory efficiency during exercise, may require reconsideration of intervention strategies. This trial was registered with the University Hospital Medical Information Network, a trial registry in Japan (registration number: UMIN000045474).

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise. We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden. Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.

Central venous-to-arterial CO2 difference as a biomarker of outcome in children who underwent surgery for congenital heart disease.

In congenital heart surgery, low cardiac output syndrome (LCOS) is a major cause of morbidity in the immediate post-operative period. A decrease in cardiac output leads to an increase in tissue oxygen consumption. Several biomarkers such as venous oxygen saturation (SvO2), arteriovenous oxygen difference (DavO2), and lactate can assess tissue perfusion in the presence of LCOS. Recently, central venous to arterial CO2 difference (ΔCO2) has been proposed as a biomarker of tissue ischemia that could be used as a predictor of death in neonatal patients. This study aimed to analyze the relationship between ΔCO2 and immediate post-operative outcomes in pediatric patients undergoing congenital heart surgery and its correlation with DavO2, SvO2, and lactate. We conducted a longitudinal study of patients aged 0-18 years who underwent congenital heart surgery with or without cardiopulmonary bypass at the Instituto Nacional de Pediatría, from March 2019 to March 2021. Eighty-two patients were included; the median age was 17 months. About 59% had a ΔCO2 ≥ 6 mmHg. Patients with ΔCO2 ≥ 6 mmHg had a vasoactive-inotropic score > 5 (p < 0.001), DavO2 > 5 mL/dL (p = 0.048), and lactate > 2 mmol/L (p = 0.027), as well as a longer hospital stay (p = 0.043). Patients with ΔCO2 > 6 mmHg and vasoactive-inotropic score ≥ 10 were 12.6 times more likely to die. ΔCO2 is a good marker of tissue hypoperfusion and outcome in the post-operative period of congenital heart surgery.

Age, sex, endurance capacity, and chronic heart failure affect central and peripheral factors of oxygen uptake measured by non-invasive and continuous technologies: support of pioneer work using invasive or non-continuous measures.

It is known that maximum oxygen uptake depends on age, sex, endurance capacity, and chronic heart failure. However, due to the required invasive or often applied non-continuous approaches, less is known on underlying central and peripheral factors. Thus, this study aimed to investigate the effects of age, sex, endurance capacity, and chronic heart failure on non-invasively and continuously measured central and peripheral factors of oxygen uptake. 15 male children (11 ± 1 years), 15 male (24 ± 3 years) and 14 female recreationally active adults (23 ± 2 years), 12 male highly trained endurance athletes (24 ± 3 years), and 10 male elders (59 ± 6 years) and 10 chronic heart failure patients (62 ± 7 years) were tested during a cardiopulmonary exercise test on a cycling ergometer until exhaustion for: blood pressure, heart rate, stroke volume, cardiac output, cardiac power output, vastus lateralis muscle oxygen saturation, and (calculated) arterio-venous oxygen difference. For the non-invasive and continuous measurement of stroke volume and muscle oxygen saturation, bioreactance analysis and near-infrared spectroscopy were used, respectively. A two-factor repeated measure ANOVA and partial eta-squared effect sizes () were applied for statistical analyses at rest, 80, and 100% of oxygen uptake. For the age effect, there were statistically significant group differences for all factors (p ≤ .033; ). Concerning sex, there were group differences for all factors (p ≤ .010; ), except diastolic blood pressure and heart rate (p ≥ .698; ). For the effect of endurance capacity, there were no group differences for any of the factors (p ≥ .065; ). Regarding chronic heart failure, there were group differences for the heart rate and arterio-venous oxygen difference (p ≤ .037; ). Age, sex, endurance capacity, and chronic heart failure affect central and peripheral factors of oxygen uptake measured by non-invasive and continuous technologies. Since most of our findings support pioneer work using invasive or non-continuous measures, the validity of our applied technologies is indirectly confirmed. Our outcomes allow direct comparison between different groups serving as reference data and framework for subsequent studies in sport science and medicine aiming to optimise diagnostics and interventions in athletes and patients.

Assessment of oxygen extraction rate changes following red blood cell transfusion in the intensive care unit: a protocol for a prospective observational non-interventional study

IntroductionHaemoglobin transfusion thresholds have been used in the intensive care unit (ICU) to guide red blood cell transfusion (RBCT) decisions. Recent research has also focused on physiological indicators of tissue...

Characterization and prognostic importance of chronotropic incompetence in heart failure with preserved ejection fraction

BackgroundExercise intolerance is the primary symptom of patients with heart failure with preserved ejection fraction (HFpEF). Chronotropic incompetence has been considered to be common and contribute to poor exercise capacity in HFpEF. However, clinical characteristics, pathophysiology, and outcomes of chronotropic incompetence in HFpEF remain poorly understood. MethodsPatients with HFpEF (n = 246) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. The patients were divided into two groups based on the presence of chronotropic incompetence, which was defined by heart rate reserve <0.80. ResultsChronotropic incompetence was common in HFpEF (n = 112, 41 %). Compared to HFpEF patients with a normal chronotropic response (n = 134), those with chronotropic incompetence had higher body mass index, a higher prevalence of diabetes, more frequent β-blocker use, and worse New York Heart Association class. During peak exercise, patients with chronotropic incompetence demonstrated less increase in cardiac output and arterial oxygen delivery (cardiac output × saturation × hemoglobin × 1.34 × 10), higher metabolic work (peak oxygen consumption [VO2]/watt), an inability to increase arteriovenous oxygen difference, and poorer exercise capacity (lower peak VO2) than those without. Chronotropic incompetence was associated with higher rates of a composite of all-cause mortality or worsening HF events (hazard ratio, 2.66, 95 % confidence intervals, 1.16–6.09, p = 0.02). ConclusionChronotropic incompetence is common in HFpEF, and is associated with unique pathophysiologic characteristics during exercise and clinical outcomes.

Cardiac output and arteriovenous oxygen difference contribute to lower peak oxygen uptake in patients with fibromyalgia

BackgroundPatients with fibromyalgia (FM) exhibit low peak oxygen uptake (dot{text{V}}O2peak). We aimed to detect the contribution of cardiac output to (dot{text{Q}}) and arteriovenous oxygen difference [text{C}(text{a-v})text{O}_{2}] to dot{text{V}}text{O}_{2} from rest to peak exercise in patients with FM.MethodsThirty-five women with FM, aged 23 to 65 years, and 23 healthy controls performed a step incremental cycle ergometer test until volitional fatigue. Alveolar gas exchange and pulmonary ventilation were measured breath-by-breath and adjusted for fat-free body mass (FFM) where appropriate. dot{text{Q}} (impedance cardiography) was monitored. text{C}(text{a-v})text{O}_{2} was calculated using Fick’s equation. Linear regression slopes for oxygen cost (∆dot{text{V}}O2/∆work rate) and dot{text{Q}} to text{V}O2 (∆dot{text{Q}}/∆dot{text{V}}O2) were calculated. Normally distributed data were reported as mean ± SD and non-normal data as median [interquartile range].Resultsdot{text{V}}O2peak was lower in FM patients than in controls (22.2 ± 5.1 vs. 31.1 ± 7.9 mL∙min−1∙kg−1, P < 0.001; 35.7 ± 7.1 vs. 44.0 ± 8.6 mL∙min−1∙kg FFM−1, P < 0.001). dot{text{Q}} and C(a-v)O2 were similar between groups at submaximal work rates, but peak dot{text{Q}} (14.17 [13.34–16.03] vs. 16.06 [15.24–16.99] L∙min−1, P = 0.005) and C(a-v)O2 (11.6 ± 2.7 vs. 13.3 ± 3.1 mL O2∙100 mL blood−1, P = 0.031) were lower in the FM group. No significant group differences emerged in ∆dot{text{V}}O2/∆work rate (11.1 vs. 10.8 mL∙min−1∙W−1, P = 0.248) or ∆dot{text{Q}}/∆dot{text{V}}O2 (6.58 vs. 5.75, P = 0.122) slopes. ConclusionsBoth dot{text{Q}} and C(a-v)O2 contribute to lower dot{text{V}}O2peak in FM. The exercise responses were normal and not suggestive of a muscle metabolism pathology.Trial registrationClinicalTrials.gov, NCT03300635. Registered 3 October 2017—Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03300635.