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Competing Interests: Conflict of interest: A.R.T. has participated in advisory boards for Janssen and Merck Pharmaceuticals. All other authors have no financial conflicts.

Objectives: To evaluate the agreement of cardiac index (CI) calculated by Ultrasonic sonic cardiac output monitor (USCOM) and transthoracic thoracic echocardiography (TTE) in order to know if we can recommend USCOM in our pediatric intensive care unit (PICU)., Design: Prospective observational evaluative study carried out over a period of 3 months Setting: PICU at children's hospital in Tunis Participants: All newborns without tracheostomy or a known congenital heart disease, admitted to the PICU during the study period were enrolled., Interventions: Paired and consecutive measurements of CI were obtained in all patients with both technologies. All measurements by TTE and USCOM were performed by two distinct operators. It is the average of three successive measures of the CI, in the same patient, with each technology, which was considered. Agreement of CI between the 2 techniques was assessed by Bland-Altman analysis and percentage error., Measurements and Main Results: Forty-two infants were analyzed with the mean (standard deviation) gestation 36 weeks ( 5 days), age 1 days (1.09) , and weight 2.9 kg (0.87). Respiratory failure was the main cause of admission 75%. At the time of the study, 33 (75.%) patients were ventilated artificially. Bias (mean difference) of the CI between the two methods was 1.2 l/min/m2 and precision (± 2 SD of differences) was 1.08 l/min/m2. The MPE of CI measurement for USCOM vs TTE was 54.9%., Conclusions: The USCOM showed a poor agreement to TTE measures of CI. The two methods cannot be considered interchangeable.

Purpose: We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A 1 ) due to lower vagal activity in H than N., Methods: Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O 2  = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method., Results: Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg -1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg -1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg -1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg -1 (p < 0.01 vs. rest). CO-A 1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min -1 in N and H, respectively (p = 0.06). HR-A 1 was 7.7 ± 4.6 and 7.1 ± 5.9 min -1 in N and H, respectively (p = 0.81)., Conclusion: The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive., (© 2024. The Author(s).)

Preterm birth elicits long-lasting physiological effects in various organ systems, potentially modulating exercise and environmental stress responses. To establish whether prematurely-born adults respond uniquely during early high-altitude acclimatization at rest and during exercise, 17 healthy adults born preterm (gestational age < 32 wk) and 17 term-born, age- and aerobic-capacity-matched, control participants completed a three-day high-altitude sojourn (3,375 m). Oxygen uptake, pulmonary ventilation, and hemodynamic responses, as well as pulse oxygen saturation, brain tissue saturation index (TSI), and skeletal muscle TSI, were measured daily at rest and during moderate-intensity steady-state exercise bouts. In general, the prematurely-born group displayed comparable acclimatization responses at rest, with similar ventilation and cardiac output observed between groups throughout. Resting brain TSI was, however, higher in the preterm group upon arrival at high altitude (72 ± 7% vs. 68 ± 3%; d = 1.20). Absolute exercising oxygen uptake was lower in the preterm participants ( P = 0.047), with this group displaying lower exercising cardiac output underpinned by reduced stroke volume (both P = 0.035). Nevertheless, exercising minute ventilation (V̇e) did not differ between groups ( P = 0.237) while brain TSI (70 ± 6% vs. 66 ± 3%; d = 1.35) and pulse oxygen saturation (85 ± 3% vs. 82 ± 5%; d = 1.52) were higher with prematurity upon arrival to high altitude. These findings suggest that healthy prematurely-born adults exhibit comparable early acclimatization patterns to their term-born counterparts and better maintain cerebral oxygenation at rest. Together, these data suggest that prematurely-born adults should not be discouraged from high-altitude sojourns involving physical activity. NEW & NOTEWORTHY The acclimatization pattern across three days at 3,375 m, at rest and during moderate-intensity exercise, was similar between healthy adults born prematurely and their term-born counterparts. Preterm adults free from respiratory complications were found to better maintain brain tissue and capillary oxygen saturation at high altitudes, whereas the term-born group experienced larger altitude-induced reductions. Despite apparent cardiac limitations, preterm individuals tolerated exercise similarly to their term-born peers. These findings underscore the notion that preterm birth per se does not predispose healthy adults to decreased altitude tolerance during exercise.

Rationale: Blood flow rate affects mixed venous oxygenation (Sv O 2 ) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: To describe the physiologic effects of different levels of Sv O 2 obtained by changing ECMO blood flow in patients with severe acute respiratory distress syndrome receiving ECMO and controlled mechanical ventilation. Methods: Low (Sv O 2 target, 70-75%), intermediate (Sv O 2 target, 75-80%), and high (Sv O 2 target, >80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography. Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/Sv O 2 (9.2 [6.2-10.9] vs. 8.3 [5.9-9.8] vs. 7.9 [6.5-9.1] L/min; P  = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs. 31 ± 6 vs. 30 ± 5 mm Hg; P  < 0.001) and right ventricular stroke work index (14.2 ± 4.4 vs. 12.2 ± 3.6 vs. 11.4 ± 3.2 g × m/beat/m 2 ; P  = 0.002). Cardiac output was inversely correlated with mixed venous and arterial Po 2 values ( R 2  = 0.257; P  = 0.031; and R 2  = 0.324; P  = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous Po 2 ( R 2  = 0.29; P  < 0.001) and with increasing cardiac output ( R 2  = 0.378; P  < 0.007). Measures of [Formula: see text]/[Formula: see text] mismatch did not differ between the three steps. Conclusions: In patients with severe acute respiratory distress syndrome, increased ECMO blood flow rate resulting in higher Sv O 2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Purpose of Review: In this review, we provide an overview of the prognostic implications of exPH in patients with various common cardiac and pulmonary diseases., Recent Findings: Exercise pulmonary hypertension (exPH) has been recently re-introduced in the current European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines. Accordingly, exPH is defined as a mean pulmonary arterial pressure (mPAP)/cardiac output ( CO ) slope greater than 3 mmHg/l/min. Key considerations for this re-introduction included increasing understanding on normal pulmonary hemodynamics during exercise and the broadly available evidence on the association of an abnormal mPAP/ CO slope with poor survival in the general population and in different disease entities., Summary: Exercise (patho-)physiology has opened a new field for clinical research facilitating recognition of cardiovascular and pulmonary vascular diseases in an early stage. Such early recognition with significant prognostic and possibly therapeutic relevance, but being undetectable at rest, makes exercise pulmonary hemodynamics particularly interesting for common diseases, such as valvular heart disease, left heart disease, and chronic pulmonary disease., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress tolerability of the alveolar-capillary unit. This study examined the effect of ultramarathon trail racing at different altitudes (ranging from <1000 m to between 1500 and 2700 m) on alveolar-capillary recruitment and lung diffusion., Methods: Cardiac and lung function were examined before and after an ultramarathon in 67 runners (age: 41 ± 9 yr, body mass index: 23 ± 2 kg·m -2 , 10 females), and following 12-24 h of recovery in a subset ( n = 27). Cardiac biomarkers (cTnI and BNP) were assessed from whole blood, whereas lung fluid accumulation (comet tails), stroke volume (SV), and cardiac output ( Q ) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semirecumbent cycling (20, 30, and 40 W)., Results: Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± 0.02 vs 0.13 ± 0.03 ng·mL -1 , BNP: 20 ± 2 vs 112 ± 21 pg·mL -1 ; P < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, P < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 mL, 40 W: 93 ± 2 vs 88 ± 2 mL; P < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 L·min -1 , P < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 L·min -1 , P = 0.899). Resting DLco and Vc decreased after the race ( P < 0.01), whereas Dm was unchanged ( P = 0.465); however, during the three stages of exercise, DLco, Vc, and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL·min -1 ·mm Hg -1 , 83 ± 3 vs 73 ± 2 mL, 186 ± 6 vs 170 ± 7 mL·min -1 ·mm Hg -1 , respectively; P < 0.01). When corrected for alveolar volume and Q , DLco decreased from pre- to post-race ( P < 0.01), and changes in DLco were similar for all ultramarathon events ( P > 0.05)., Conclusions: Competing in an ultramarathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar-capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultramarathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF., Methods and Results: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e ' (exE/ e ') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/ e '<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/ e '≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/ e '<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/ e '<15 but a high slope had NT-proBNP levels and H 2 FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope., Conclusions: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Background: The selection of adequate indicators of tissue hypoxia for guiding the resuscitation process of septic patients is a highly relevant issue. Current guidelines advocate for the use of lactate as sole metabolic marker, which may be markedly limited, and the integration of different variables seems more adequate. In this study, we explored the metabolic profile and its implications in the response to the administration of a fluid challenge in early septic shock patients., Methods: Observational study including septic shock patients within 24 h of ICU admission, monitored with a cardiac output estimation system, with ongoing resuscitation. Hemodynamic and metabolic variables were measured before and after a fluid challenge (FC). A two-step cluster analysis was used to define the baseline metabolic profile, including lactate, central venous oxygen saturation (ScvO 2 ), central venous-to-arterial carbon dioxide difference (PcvaCO 2 ), and PcvaCO 2 corrected by the difference in arterial-to-venous oxygen content (PcvaCO 2 /CavO 2 )., Results: Seventy-seven fluid challenges were analyzed. Cluster analysis revealed two distinct metabolic profiles at baseline. Cluster A exhibited lower ScvO 2 , higher PcvaCO 2 , and lower PcvaCO 2 /CavO 2 . Increases in cardiac output (CO) were associated with increases in VO 2 exclusively in cluster A. Baseline isolated metabolic variables did not correlate with VO 2 response, and changes in ScvO 2 and PcvaCO 2 were associated to VO 2 increase only in cluster A., Conclusions: In a population of early septic shock patients, two distinct metabolic profiles were identified, suggesting tissue hypoxia or dysoxia. Integrating metabolic variables enhances the ability to detect those patients whose VO 2 might increase as results of fluid administration., (© 2024. The Author(s).)

Cardiac output (Q̇ C ) and leg blood flow (Q̇ LEG ) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of Q̇ LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇ LEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. Q̇ LEG and Q̇ C were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (V̇O 2peak ) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇ LEG (19.0 vs. 19.5 L/min) and Q̇ C (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% V̇O 2peak ). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O 2peak ). In summary, we present the first direct measure of Q̇ LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇ LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background and Aim: Assisted mechanical ventilation may alter the pressure profile in the thorax compared to normal breathing, which can affect the blood flow to and from the heart. Studies suggest that in patients with severe lung disease, airway pressure release ventilation (APRV) may be haemodynamically beneficial compared to other ventilator settings. The primary aim of this study was to investigate if APRV affects cardiac index in intubated intensive care patients without severe lung disease when compared to pressure support ventilation (PSV). The secondary aim comprised potential changes in other haemodynamic and ventilatory parameters., Methods: Twenty patients were enrolled in the intensive care unit (ICU) at Sahlgrenska University Hospital. Eligible patients met the inclusion criteria; 18 years of age or above, intubated and mechanically ventilated, triggering and stable on PSV mode, with indwelling haemodynamic monitoring via a pulse-induced continuous cardiac output (PiCCO) catheter. The study protocol started with a 30-min interval on PSV mode, followed by a 30-min interval on APRV mode, and finally a 30-min interval back on PSV mode. At the end of each interval, PiCCO outputs, ventilator outputs, arterial and venous blood gas analyses, heart rate and central venous pressure were recorded and compared between modes., Results: There was no significant difference in cardiac index (3.42 vs. 3.39 L/min/m 2 ) between PSV and APRV, but a significant increase in central venous pressure (+1.0 mmHg, p = .027). Furthermore, we found a significant reduction in peak airway pressure (-3.16 cmH 2 O, p < .01) and an increase in mean airway pressure (+2.1 cmH 2 O, p < .01). No statistically significant change was found in oxygenation index (partial pressure of O 2 [pO 2 ]/fraction of inspired oxygen) nor in other secondary outcomes when comparing PSV and APRV. There was no significant association between global end-diastolic volume index and cardiac index (R 2  = 0.0089) or central venous pressure (R 2  = 0.278). All parameters returned to baseline after switching the ventilator mode back to PSV., Conclusion: We could not detect any changes in cardiac index in ICU patients without severe lung disease during APRV compared to PSV mode, despite lower peak airway pressure and increased mean airway pressure., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

The presence of cardiac shunts in ectothermic tetrapods is thought to be consistent with active vascular modulations for proper hemodynamic support. Local control of blood flow modulates tissue perfusion and thus systemic conductance (Gsys) is assumed to increase with body temperature (Tb) to accommodate higher aerobic demand. However, the general increase of Gsys presses for a higher right-to-left (R-L) shunt, which reduces arterial oxygen concentration. In contrast, Tb reduction leads to a Gsys decrease and a left-to-right shunt, which purportedly increases pulmonary perfusion and plasma filtration in the respiratory area. This investigation addressed the role of compensatory vascular adjustments in the face of the metabolic alterations caused by Tb change in the South American rattlesnake (Crotalus durissus). Cardiovascular recordings were performed in decerebrated rattlesnake preparations at 10, 20 and 30°C. The rise in Tb increased metabolic demand, and correlated with an augmentation in heart rate. Although cardiac output increased, systemic stroke volume reduced while pulmonary stroke volume remained stable. Although that resulted in a proportionally higher increase in pulmonary blood flow, the R-L shunt was maintained. While the systemic compliance of large arteries was the most relevant factor in regulating arterial systemic blood pressure, peripheral conductance of pulmonary circulation was the major factor influencing the final cardiac shunt. Such dynamic adjustment of systemic compliance and pulmonary resistance for shunt modulation has not been demonstrated before and contrasts with previous knowledge on shunt control., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The aortic valve (AV) is crucial for cardiovascular (CV) hemodynamic, impacting cardiac output (CO) and left ventricular volumetric flow rate (LVQ). Its nonlinear behavior challenges standard LVQ prediction methods as well as CO one. This study presents a novel approach for modeling the AV in the CV system, offering an improved method for estimating crucial parameters like LVQ across various AV conditions, including aortic stenosis (AS). The model, based on AV channel length during the entire cardiac phase, introduces a time-varying AV resistance (TV-AVR) parameterized by the pressure ratio across the AV and LVQ, enabling the simulation of both healthy and AS-related conditions. To validate this model, in vitro measurements are compared using a hybrid mock circulatory loop device. An unconventional use of a convolutional neural network (CNN) corrects the model's estimates, eliminating the need for labeled datasets. This approach, incorporating real-time learning and transforming 1-D CV signals into 2-D tensors, significantly improves the accuracy of LVQ measurements, achieving an error rate of less than 3.41 ± 4.84% for CO in healthy conditions and 2.83 ± 1.35% in AS cases-a 33.13% enhancement over linear diode models. These results underscore the potential of this approach for enhancing the diagnosis, prediction, and treatment of AV diseases. The key contributions of the proposed method encompass nonlinear TV-AVR estimation, investigation of transient CV responses, prediction of instantaneous CO, development of a flexible framework for noninvasive measurements integration, and the introduction of an adjustable resistance model using an extended Kalman filter (EKF) and CNN combination, all without requiring labeled data., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Background: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation., Methods: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO 2 ) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO 2 slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO 2 , and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity., Results: Peak VO 2 during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P =0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO 2 /dL blood; P <0.001). During single leg knee extension, there was no difference in peak leg VO 2 ( P =0.306), but the peripherally limited group had greater blood flow/VO 2 ratio ( P =0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO 2 /dL blood; P =0.013), and lower muscle oxygen diffusive conductance ( P =0.021). A difference in magnetic resonance spectroscopy-derived phosphocreatine recovery time was not detected ( P =0.199)., Conclusions: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O 2 ratio and poor muscle diffusive capacity., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844., Competing Interests: None.

Context: Energy drinks (EDs) are beverages that contain ingredients that may pose a risk to consumers' cardiovascular health. But current evidence is conflicting and warrants further investigation., Objective: A systematic review and meta-analysis was conducted on studies that examined the acute effects of ED consumption on systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate, cardiac output (CO), endothelial function, and QT/QTc interval in healthy adults., Data Sources: The databases PubMed, EMBASE, Cochrane, LILACS, Web of Science, SportDiscus, and the gray literature were searched to identify randomized controlled trials (RCTs)., Data Extraction: Two independent evaluators screened 2014 studies and extracted relevant data from those selected for the analysis. A risk of bias assessment was also performed with the RoB 2 tool and a strength of evidence assessment was performed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE)., Data Analysis: A total of 17 RCTs were included in the meta-analysis. With regard to risk of bias, 11 studies were rated as having "some concerns" and 6 as "high risk of bias." The consumption of EDs increased SBP, DBP, and CO in different time frames. More pronounced effects were seen on SBP at 60-80 minutes (4.71 mmHg; 95% CI: 2.97-6.45; GRADE: moderate), DBP at 120 minutes (4.51 mmHg; 95% CI: 2.60-6.42; GRADE: low), and CO at 30-40 minutes after consumption (0.43 L; 95% CI: 0.08-0.77; GRADE: very low). The effects of ED consumption on resting heart rate and QT/QTc interval were not significant (P ≤ 0.05). The assessment of endothelial function effects was not performed due to the absence of any RCTs meeting the inclusion criteria., Conclusions: Acute consumption of EDs increases SBP, DBP, and CO in healthy adults. However, no alterations were observed in other cardiovascular parameters. The results should be interpreted with caution due to the limited number of studies included in the analysis., Systematic Review Registration: PROSPERO registration no. CRD42022295335., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Compensatory Reserve Metric (CRM) provides a time sensitive indicator of hemodynamic decompensation. However, its in-field utility is limited because of the size and cost-intensive nature of standard vital sign monitors or photoplethysmographic volume-clamp (PPG VC ) devices used to measure arterial waveforms. In this regard, photoplethysmographic measurements obtained from pulse oximetry may serve as a useful, portable alternative. This study aimed to validate CRM values obtained using pulse oximeter (PPG PO )., Methods: Forty-nine healthy adults (25 females) underwent a graded lower body negative pressure (LBNP) protocol to simulate hemorrhage. Arterial waveforms were sampled using PPG PO and PPG VC . The CRM was calculated using a one-dimensional convolutional neural network. Cardiac output and stroke volume were measured using PPG VC . A brachial artery catheter was used to measure intra-arterial pressure. A three-lead electrocardiogram was used to measure heart rate. Fixed-effect linear mixed models with repeated measures were used to examine the association between CRM values and physiologic variables. Log-rank analyses were used to examine differences in shock determination during LBNP between monitored hemodynamic parameters., Results: The median LBNP stage reached was 70 mm Hg (range, 45-100 mm Hg). Relative to baseline, at tolerance, there was a 47% ± 12% reduction in stroke volume, 64% ± 27% increase in heart rate, and 21% ± 7% reduction in systolic blood pressure ( p < 0.001 for all). Compensatory Reserve Metric values obtained with both PPG PO and PPG VC were associated with changes in heart rate ( p < 0.001), stroke volume ( p < 0.001), and pulse pressure ( p < 0.001). Furthermore, they provided an earlier detection of hemodynamic shock relative to the traditional metrics of shock index ( p < 0.001 for both), systolic blood pressure ( p < 0.001 for both), and heart rate ( p = 0.001 for both)., Conclusion: The CRM obtained from PPG PO provides a valid, time-sensitized prediction of hemodynamic decompensation, opening the door to provide military medical personnel noninvasive in-field advanced capability for early detection of hemorrhage and imminent onset of shock., Level of Evidence: Diagnostic Tests or Criteria; Level III., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

The transition from intrauterine to extrauterine life is a critical period for neonates. Assessing the cardiovascular transition during this period immediately after birth is crucial but challenging. The present study compares adjusted estimated cardiac output values calculated by the Liljestrand and Zander formula (COest/adj LaZ) with non-invasively measured cardiac output values (CO-bioimpedance) during immediate transition after birth. We performed a secondary outcome analysis of a prospective observational study in preterm and term neonates. Ten and 15 min after birth, arterial blood pressure and heart rate were assessed, and CO-bioimpedance was measured using electrical bioimpedance method (Aesculon monitor, Osypka, Germany). We calculated COest/adj LaZ and compared it to CO-bioimpedance. Further, we performed a correlation analysis. Thirty-two neonates with a median (IQR) gestational age of 37.0 (32.0-39.4) weeks were included. Mean ± SD CO-bioimpedance was 0.62 ± 0.15 l/min, and COest/adj LaZ was calculated to be 0.64 ± 0.10 l/min, whereby both correlated significantly (p = 0.025, r = 0.359) with each other.  Conclusion: The present study demonstrates high comparability of COest/adj LaZ and CO-bioimpedance in neonates during immediate transition after birth, suggesting that cardiac output can be derived in a cost-effective and feasible manner if other methods are not available. What is Known: • Echocardiography is considered the gold standard for non-invasive CO evaluation, but its feasibility during the immediate transition period is limited. What is New: • Non-invasive methods such as CO-bioimpedance for cardiac output (CO) measurement and the Liljestrand and Zander (LaZ) formula for estimating CO offer promising alternatives during the immediate transition period., (© 2024. The Author(s).)

Background and Objectives : To evaluate the effects of the pulse index continuous cardiac output and MostCare Pressure Recording Analytical Method hemodynamic monitoring systems on short-term graft and patient outcomes during living donor liver transplantation in adult patients. Materials and Methods : Overall, 163 adult patients who underwent living donor liver transplantation between January 2018 and March 2022 and met the study inclusion criteria were divided into two groups based on the hemodynamic monitoring systems used during surgery: the MostCare Pressure Recording Analytical Method group ( n = 73) and the pulse index continuous cardiac output group ( n = 90). The groups were compared with respect to preoperative clinicodemographic features (age, sex, body mass index, graft-to-recipient weight ratio, and Model for End-stage Liver Disease score), intraoperative clinical characteristics, and postoperative biochemical parameters (aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, prothrombin time, international normalized ratio, and platelet count). Results : There were no significant between-group differences with respect to recipient age, sex, body mass index, graft-to-recipient weight ratio, Child, Model for End-stage Liver Disease score, ejection fraction, systolic pulmonary artery pressure, surgery time, anhepatic phase, cold ischemia time, warm ischemia time, erythrocyte suspension use, human albumin use, crystalloid use, urine output, hospital stay, and intensive care unit stay. However, there was a significant difference in fresh frozen plasma use ( p < 0.001) and platelet use ( p = 0.037). Conclusions : The clinical and biochemical outcomes are not significantly different between pulse index continuous cardiac output and MostCare Pressure Recording Analytical Method as hemodynamic monitoring systems in living donor liver transplantation. However, the MostCare Pressure Recording Analytical Method is more economical and minimally invasive.

Background: Assessment of regional ventilation/perfusion (V'/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V'/Q mismatch., Methods: We enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V'/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V'/Q-ABS), left unadjusted (V'/Q-REL), or corrected by MV/CO ratio derived from EIT data (V'/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units ( V D ' /Q SHUNT ) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (Q ND / V DS ' ) was calculated as an index of hypocapnic pneumoconstriction., Results: Our calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V'/Q-ABS, V'/Q-REL maps overestimated ventilation (p = 0.013) and perfusion (p = 0.002) to low V'/Q units and underestimated ventilation (p = 0.011) and perfusion (p = 0.008) to high V'/Q units. The heterogeneity of ventilation and perfusion reaching different V'/Q compartments was underestimated. V'/Q-CORR maps eliminated all these differences with V'/Q-ABS (p > 0.05). Higher V D ' / Q SHUNT correlated with higher PaO 2 /FiO 2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ =  - 0.59, p = 0.005). Higher Q ND / V DS ' correlated with lower PEEP (ρ =  - 0.62, p = 0.003) and plateau pressure (ρ =  - 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days (p = 0.05 and p = 0.03, respectively)., Conclusions: Regional V'/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes., (© 2024. The Author(s).)

Objective: To investigate the accuracy, precision, and trending ability of noninvasive bioreactance-based Starling SV and the mini invasive pulse-power device LiDCOrapid as compared to thermodilution cardiac output (TDCO) as measured by pulmonary artery catheter when assessing cardiac index (CIx) in the setting of elective open abdominal aortic (AA) surgery., Design: A prospective method-comparison study., Setting: Oulu University Hospital, Finland., Participants: Forty patients undergoing elective open abdominal aortic surgery., Interventions: Intraoperative CI measurements were obtained simultaneously with TDCO and the study monitors, resulting in 627 measurement pairs with Starling SV and 497 with LiDCOrapid., Measurements and Main Results: The Bland-Altman method was used to investigate the agreement among the devices, and four-quadrant plots with error grids were used to assess trending ability. The agreement between TDCO and Starling SV was associated with a bias of 0.18 L/min/m 2 (95% confidence interval [CI] = 0.13 to 0.23), wide limits of agreement (LOA = -1.12 to 1.47 L/min/m 2 ), and a percentage error (PE) of 63.7 (95% CI = 52.4-71.0). The agreement between TDCO and LiDCOrapid was associated with a bias of -0.15 L/min/m 2 (95% CI = -0.21 to -0.09), wide LOA (-1.56 to 1.37), and a PE of 68.7 (95% CI = 54.9-79.6). The trending ability of neither device was sufficient., Conclusion: The CI measurements achieved with Starling SV and LiDCOrapid were not interchangeable with TDCO, and the ability to track changes in CI was poor. These results do not support the use of either study device in monitoring CI during open AA surgery., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Osmotherapeutic agents increase the intravascular volume by withdrawing water from the brain followed by relative hypovolemia due to diuresis leading to significant changes in systemic hemodynamics which might have adverse consequences in the elderly. We studied the effect of mannitol (20%) and hypertonic saline (HTS) (3%) on left ventricular outflow tract velocity time integral (LVOT-VTI) and cardiac output (CO) in elderly patients undergoing supratentorial neurosurgical procedures using transesophageal echocardiography., Methods: We recruited 28 patients aged above 65 years undergoing supratentorial craniotomy who received equiosmolar solutions of 5.35 ml/kg of 3% HTS (group HS, n = 14) or 5 ml/kg of 20% mannitol (group M, n = 14). LVOT-VTI was recorded at baseline, 15, 30, 45, 60, and 90 minutes postinfusion and CO was derived. We also recorded heart rate, blood pressure, fluid balance, brain relaxation, vasopressor use, complications, and neurological outcome., Results: We found a significant decrease in LVOT-VTI at 45, and 60 minutes in group M as compared to group HS [mean (standard deviation), 16.76 (1.81) vs. 20.78 (1.87), P < 0.001, 17.4 (2.38) vs. 19.16 (2), P = 0.044, respectively]. We also found a corresponding significant fall in CO [3863.16 (845.87) vs. 4745.59 (1209.33) ml/minute, P = 0.034] and systolic blood pressure (P = 0.039), at 45 minutes in group M. Urine output was higher in group M (P < 0.001). All other parameters were comparable., Conclusions: HTS appears to be associated with better systemic hemodynamics (LVOT-VTI, CO) while providing equivalent brain relaxation as mannitol in elderly patients. A future larger study is required to confirm our preliminary findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to assess the acute impact of distinct loading breathing types and intensities on cardiac autonomic function and hemodynamic responses in healthy young adults., Methods: A randomized, crossover trial involved 28 participants who underwent inspiratory resistive breathing, expiratory resistive breathing (ERB) and combined resistive breathing, each at 30% and 60% of maximal respiratory pressures. Data on heart rate variability (HRV) and hemodynamic parameters were collected during each trial., Results: The study revealed significant main and interaction effects for both the performed task and the intensity across all measured variables (all p < 0.001). ERB at 60% load demonstrated significantly higher HRV values in the standard deviation of normal-to-normal RR intervals, the square root of the mean squared difference of successive normal-to-normal RR intervals and high-frequency power, as well as significantly lower values in heart rate, stroke volume, stroke volume index, cardiac output, cardiac index, end-diastolic volume and end-diastolic volume index, compared to other loaded protocols (all p < 0.001)., Conclusion: These findings highlight the acute effect of type-specific and load-dependent resistive breathing on cardiac autonomic and hemodynamic functions, where ERB at 60% intensity showed the most significant cardiovagal modulation while causing the least hemodynamic alterations., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Cardiovascular responses to diving are characterized by two opposing responses: tachycardia resulting from exercise and bradycardia resulting from the apnea. The convergence of bradycardia and tachycardia may determine the cardiovascular responses to diving. The purpose of this study was to investigate the interaction of breath holding and muscle mechanoreflex on cardiovascular responses in breath-hold divers (BHDs) and non-BHDs. We compared the cardiovascular responses to combined apnea and the mechanoreflex in BHDs and non-BHDs. All participants undertook three trials-apnea, passive leg cycling (PLC), and combined trials-for 30 s after rest. Cardiovascular variables were measured continuously. Nine BHD (male:female, 4:5; [means ± SD] age, 35 ± 6 years; height, 168.6 ± 4.6 cm; body mass, 58.4 ± 5.9 kg) and eight non-BHD (male:female, 4:4; [means ± SD] age, 35 ± 7 years; height, 163.9 ± 9.1 cm; body mass, 55.6 ± 7.2 kg) participants were included. Compared to the resting baseline, heart rate (HR) and cardiac output (CO) significantly decreased during the combined trial in the BHD group, while they significantly increased during the combined trials in the non-BHD group (P < 0.05). Changes in the HR and CO were significantly lower in the BHD group than in the non-BHD group in the combined trial (P < 0.05). These results suggest that bradycardia with apnea in BHDs is prioritized over tachycardia with the mechanoreflex, whereas that in non-BHDs is not. This finding implies that diving training changes the interaction between apnea and the mechanoreflex in cardiovascular control., (© 2024. The Author(s).)

Objective: The purposes of the study were to develop reference ranges and maturation patterns of fetal cardiac function parameters measured by speckle tracking echocardiography (STE) using multiple biometric variables at 17 to 24 weeks' gestation among Thai fetuses and to compare with other previous reports., Study Design: The four-chamber view of the fetal heart in 79 healthy fetuses was suitably analyzed by STE to establish the best-fit regression model. The 95% reference intervals and Z -score equations of fetal cardiac function parameters were computed., Results: The fractional area change of both ventricles, left ventricular (LV) end-diastolic and end-systolic volumes, LV stroke volume, LV cardiac output (CO), and LV CO per kilogram were all increased according to gestational age (GA) and five fetal biometric measurements. However, the global longitudinal strain, basal-apical length fractional shortening (BAL-FS), BAL annular free wall and septal wall FS, BAL free wall and septal wall annular plane systolic excursions, 24-segment transverse width FS, as well as LV ejection fraction were all independent of GA or other somatic characteristics. There were varying development patterns between fetal right and left ventricles of these cardiac function indices across the gestation period., Conclusion: Our study created Z -score and corresponding centile calculators, 5th and 95th centile reference tables, and corresponding graphs and determined the normal evolution across gestation using multiple somatic growth and age variables between 17 and 24 gestational weeks. These nomograms serve as an essential prerequisite for quantitatively evaluating fetal cardiac contractility and allow for precisely detecting early changes in the fetal heart function., Key Points: · Most fetal cardiac function measurements were correlated with all the independent variables.. · Fetal ventricular function parameters have their own characteristic maturation changes.. · Racial variability may not occupy an important place for fetal myocardial function during these GA.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The likelihood of a patient being preload responsive-a state where the cardiac output or stroke volume (SV) increases significantly in response to preload-depends on both cardiac filling and function. This relationship is described by the canonical Frank-Starling curve. Research Question : We hypothesize that a novel method for phenotyping hypoperfused patients (ie, the "Doppler Starling curve") using synchronously measured jugular venous Doppler as a marker of central venous pressure (CVP) and corrected flow time of the carotid artery (ccFT) as a surrogate for SV will refine the pretest probability of preload responsiveness/unresponsiveness. Study Design and Methods: We retrospectively analyzed a prospectively collected convenience sample of hypoperfused adult emergency department (ED) patients. Doppler measurements were obtained before and during a preload challenge using a wireless, wearable Doppler ultrasound system. Based on internal jugular and carotid artery Doppler surrogates of CVP and SV, respectively, we placed hemodynamic assessments into quadrants (Q x ) prior to preload augmentation: low CVP with normal SV (Q 1 ), high CVP and normal SV (Q 2 ), low CVP and low SV (Q 3 ) and high CVP and low SV (Q 4 ). The proportion of preload responsive and unresponsive assessments in each quadrant was calculated based on the maximal change in ccFT (ccFT Δ ) during either a passive leg raise or rapid fluid challenge. Results: We analyzed 41 patients (68 hemodynamic assessments) between February and April 2021. The prevalence of each phenotype was: 15 (22%) in Q 1 , 8 (12%) in Q 2 , 39 (57%) in Q 3 , and 6 (9%) in Q 4 . Preload unresponsiveness rates were: Q 1 , 20%; Q 2 , 50%; Q 3 , 33%, and Q 4 , 67%. Interpretation: Even fluid naïve ED patients with sonographic estimates of low CVP have high rates of fluid unresponsiveness, making dynamic testing valuable to prevent ineffective IVF administration., Competing Interests: Declaration of Conflicting InterestsJESK, SOG, JKE, CH, and DHJ work for Flosonics Medical, the start-up building the wearable Doppler ultrasound. RP, PR, KH, VCL, and BOK declare no competing interests.

Objectives: Right ventricular (RV) output reserve, defined as increase of cardiac output during exercise, is reduced in patients with pulmonary arterial hypertension (PAH). Aim of this study was to evaluate the association of right heart size measured by echocardiography and invasively measured RV function at rest and during exercise in PAH patients., Methods: Adult PAH-patients who received routine haemodynamic assessment at rest and during exercise by right heart catheterisation and echocardiographic measurement of right heart size (right atrial (RA) and RV area) were included in this study. Clinical, echocardiographic, laboratory, exercise and invasive haemodynamic parameters were retrospectively analysed. The primary endpoint was to assess the association between right heart size and right ventricular function., Results: Data from 215 PAH patients (age 58.9 ± 15.9 years, 63.3% female, 62.2% double or triple combination treatment) were analysed in this cross-sectional study. Cardiac index was significantly lower for patients with enlarged RA-area > 18 cm 2 at rest, and at 25 and 50 W (all p < 0.001) and for patients with enlarged RV area > 20 cm 2 at rest, 25, 50 and 75 W (all p < 0.001). Furthermore, pulmonary vascular resistance and mPAP/CO slope (all p < 0.001) were significantly higher and pulmonary arterial compliance (all p < 0.05) was significantly lower in patients with enlarged RA or RV area. RA and RV area correlated with TAPSE/sPAP (both p < 0.001, R - 0.570 and - 0.530)., Conclusion: This study could underline that an enlargement of RA- and RV-area is associated with an impaired RV function at rest and during exercise in patients with PAH., Competing Interests: Declaration of competing interest BE: received travel fees, consulting fees, speaking fees, and/or honoraria from Janssen, MSD, Bayer and OMT, outside the submitted work. KFW, AMM: nothing to declare. CAE: received speaking fees from MSD outside the submitted work. SH: received honoraria for lectures, consultancy, or both from Actelion, AOP, Bayer/MSD, GSK, Novartis, OMT, Pfizer, and United Therapeutics out-side the submitted work. EG: has received grants and personal fees from Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, outside the submitted work. PX: has received personal fees from MSD and OMT outside the submitted work. NB: received speaker fees from University Hospital Zurich and AOP., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To assess the ability of the USCOM® (USCOM), using measurements of cardiac output (CO) and systemic vascular resistance (SVR), to predict the development of pre-eclampsia (PE) and severe PE in hypertensive pregnancies., Study Design: Prospective cohort study of women in the second or third trimester recruited at a tertiary center in Sydney, Australia. Demographic data and hemodynamic measurements using the USCOM were taken for all study participants at recruitment. Pregnancy outcome, including development of PE and severe PE, was tracked. Data were analyzed using ANOVA testing, pair-wise comparison testing, and Student's t-testing., Results: Recruitment included 65 normotensive controls, 34 women with chronic hypertension (CH), 51 with gestational hypertension (GH), and 21 with PE. Significantly higher weight, body surface area, and blood pressure measurements were found in the hypertensive, compared with the normotensive control and pregnancies. There were no observed differences in USCOM-measured CO, cardiac index, SVR, or systemic vascular resistance index between hypertensive women who did versus did not develop PE or severe PE in later pregnancy. Analysis of the CH and GH subgroups, as well as only unmedicated hypertensive women ( n  = 24), also showed no significant difference in hemodynamic parameters between those who did or did not develop PE or severe PE., Conclusions: Our group was unable to successfully predict the onset of PE or severe PE based on hemodynamic parameters measured with the USCOM. It is possible this relates to the high proportion of women on antihypertensive medication at recruitment.

Background: Invasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI., Methods: We included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise., Results: Among 84 patients, PI was identified in 57 (67.8 %). Compared to patients without PI, those with PI were younger [median (IQR) 37 (28, 46) vs 47 (39,55) years, p = 0.005] and had lower workload at peak exercise [81 (66, 96) vs 95 (83.5, 110.50) Watts, p = 0.006]. Patients with PI had higher heart rates at rest and peak exercise [87 (78, 97) vs 79 (74, 87) bpm, p = 0.04; and 167 (154, 183) vs 156 (136, 168) bpm, p = 0.01, respectively]. In all patients, epinephrine and norepinephrine at peak exercise directly correlated with peak workload (r:0.41, p < 0.001 and r:0.47, p < 0.001, respectively). Resting epinephrine was higher in patients with PI [136 (60, 210) vs 77 (41, 110) pg/mL, p = 0.02]. There was no significant difference in the change in catecholamines from rest to peak exercise between patients with or without PI., Conclusion: PI patients exhibited elevated heart rate and epinephrine at rest, indicating increased sympathetic activity. We did not find strong associations between catecholamines and cardiac filling pressures, suggesting that catecholamine levels are predominantly influenced by peak workload., Competing Interests: Declaration of competing interest The authors have no significant conflicts of interest with any companies or organizations whose products or services may be discussed in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aerobic metabolism underlies vital traits such as locomotion and thermogenesis, and aerobic capacity influences fitness in many animals. The heart is a key determinant of aerobic capacity, but the relative influence of cardiac output versus other steps in the O2 transport pathway remains contentious. In this Commentary, we consider this issue by examining the mechanistic basis for adaptive increases in aerobic capacity (thermogenic V̇O2,max; also called summit metabolism) in deer mice (Peromyscus maniculatus) native to high altitude. Thermogenic V̇O2,max is increased by acclimation to cold hypoxia (simulating high-altitude conditions), and high-altitude populations generally have greater V̇O2,max than their low-altitude counterparts. This plastic and evolved variation in V̇O2,max is associated with corresponding variation in maximal cardiac output, along with variation in other traits across the O2 pathway (e.g. arterial O2 saturation, blood haemoglobin content and O2 affinity, tissue O2 extraction, tissue oxidative capacity). By applying fundamental principles of gas exchange, we show that the relative influence of cardiac output on V̇O2,max depends on the O2 diffusing capacity of thermogenic tissues (skeletal muscles and brown adipose tissues). Functional interactions between cardiac output and blood haemoglobin content determine circulatory O2 delivery and thus affect V̇O2,max, particularly in high-altitude environments where erythropoiesis can increase haematocrit and blood viscosity. There may also be functional linkages between cardiac output and tissue O2 diffusion due to the role of blood flow in determining capillary haematocrit and red blood cell flux. Therefore, the functional interactions between cardiac output and other traits in the O2 pathway underlie the adaptive evolution of aerobic capacities., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

When calculating cardiac index (C.I.) by the Fick method, oxygen consumption (VO 2 ) is often unknown, so assumed values are typically used. This practice introduces a known source of inaccuracy into the calculation. Using a measured VO 2 (mVO 2 ) from the CARESCAPE E-sCAiOVX module provides an alternative that may improve accuracy of C.I. calculations. Our aim is to validate this measurement in a general pediatric catheterization population and compare its accuracy with assumed VO 2 (aVO 2 ). mVO 2 was recorded for all patients undergoing cardiac catheterization with general anesthesia and controlled ventilation during the study period. mVO 2 was compared to the reference VO 2 (refVO 2 ) determined by the reverse Fick method using cardiac MRI (cMRI) or thermodilution (TD) as a reference standard for measurement of C.I. when available. 193 VO 2 measurements were obtained, including 71 with a corresponding cMRI or TD measure of cardiac index for validation. mVO 2 demonstrated satisfactory concordance and correlation with the TD- or cMRI-derived refVO 2 (ρ c  = 0.73, r 2  = 0.63) with a mean bias of - 3.2% (SD ± 17.3%). Assumed VO 2 demonstrated much weaker concordance and correlation with refVO 2 (ρ c  = 0.28, r 2  = 0.31) with a mean bias of + 27.5% (SD ± 30.0%). Subgroup analysis of patients < 36 months of age demonstrated that error in mVO 2 was not significantly different from that observed in older patients. Many previously reported prediction models for assuming VO 2 performed poorly in this younger age range. Measured oxygen consumption using the E-sCAiOVX module is significantly more accurate than assumed VO 2 when compared to TD- or cMRI-derived VO 2 in a pediatric catheterization lab., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Some patients with chronic thromboembolic pulmonary hypertension (CTEPH) exhibit exercise intolerance due to reduced cardiac output (CO) even after successful balloon pulmonary angioplasty (BPA). Medical therapy is a potential option for such cases; however, it is unclear which patients necessitate it even after BPA., Methods: This study included 286 patients with CTEPH who underwent BPA and right heart catheterization 1 year after the final BPA and classified them into no-medication and withdrawal groups. The no-medication group comprised patients without pulmonary hypertension (PH) medications before and after BPA, while the withdrawal group included patients who received PH medications before BPA and discontinued them after BPA. We assessed differences in the changes in CO after BPA from baseline (ΔCO) between the 2 groups. Additionally, we evaluated the ΔCO among different age categories within each group: younger (<60 years), middle-aged (60-70 years), and older adults (≥70 years)., Results: After adjusting baseline covariates, overall CO did not differ significantly. However, ΔCO was significantly positive in the no-medication group but negative in the withdrawal group (0.32 and -0.33, difference in ΔCO: -0.65, 95% confidence intervals: -0.90 to -0.40). A significantly positive effect on ΔCO was observed in younger and middle-aged individuals, with a significant interaction between age and ΔCO in no-medication groups., Conclusions: Increasing CO with BPA alone may be challenging with age in patients with CTEPH. Given that discontinuation of PH medication after BPA decreased CO more than the effect of BPA, medical therapy might be necessary even after successful BPA., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Early recognition and prompt, appropriate management may reduce mortality in patients with sepsis. The Surviving Sepsis Campaign's guidelines suggest the use of dynamic measurements to guide fluid resuscitation in sepsis; although these methods are rarely employed to monitor cardiac output in response to fluid administration outside intensive care units. This service evaluation investigated the introduction of a nurse led protocolised goal-directed fluid management using a non-invasive cardiac output monitor to the standard assessment of hypotensive ward patients., Methods: We introduced the use of a goal-directed fluid management protocol into our critical care outreach teams' standard clinical assessment. Forty-nine sequential patients before and thirty-nine after its introduction were included in the assessment., Results: Patients in the post-intervention cohort received less fluid in the 6 h following outreach assessment (750mls vs 1200mls). There were no differences in clinical background or rates of renal replacement therapy, but rates of invasive and non-invasive ventilation were reduced (0% vs 31%). Although the groups were similar, the post-intervention patients had lower recorded blood pressures., Conclusion: IV fluid therapy in the patient with hypotension complicating sepsis can be challenging. Excessive IV fluid administration is commonplace and associated with harm, and the use of advanced non-invasive haemodynamic monitoring by trained nurses can provide objective evaluation of individualised response to treatment. Avoiding excessive IV fluid and earlier institution of appropriate vasopressor therapy may improve patient outcomes., Implications for Clinical Practice: Adoption of dynamic measures of cardiac output outside of critical care by trained critical care nurses is feasible and may translate into improved patient outcomes. In hospitals with a nurse-led critical care outreach service, consideration should be given to such an approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without a clinically apparent shock. The purpose of this study is to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy., Methods and Results: This was a single-centre retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds [odds ratio = 7.9; 95% confidence interval (CI) 3.49-18.1, P < 0.001] for an elevated CO2 gap. There was an inverse relationship between the CI and the CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (P = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved the CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in the in-hospital mortality rate (9 vs. 0%; P = 0.10; hazard ratio: 1.24; 95% CI 0.97-1.60; P = 0.085)., Conclusion: Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to the CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification., Competing Interests: Conflict of interest: S.B.—advisory board—Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, and Argon. J.M.H.—funding from Inari Medical. The remaining authors report no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cardiac complications are a rare but potentially serious consequence of hyperbaric oxygen treatment (HBOT), resulting from increased blood pressure and decreased heart rate and cardiac output associated with treatment. These physiologic changes are generally well-tolerated by patients without preexisting cardiac conditions, although those with known or undetected cardiac disease may be more vulnerable to treatment complications. Currently, there are no universally accepted guidelines for pre-HBOT cardiac screening to identify these patients at heightened risk, leading to variability in practice patterns. In the absence of HBOT-specific evidence, screening protocols might be adapted from the diving medicine community; however, given the important differences in physiological stressors, these may not be entirely applicable to patients undergoing HBOT. Traditional cardiac investigations such as electro- and echo-cardiograms are limited in their ability to detect relevant risk modifying states in the pre-HBOT patient, stymieing their cost-effectiveness as routine tests. In the absence of strong evidence to support routine cardiac investigation, we argue that a comprehensive history and physical exam - tailored to identify high-risk patients based on clinical parameters - may serve as a more practical screening tool. While certain unique patient groups such as those undergoing dialysis or with implanted cardiac devices may warrant specialised assessment, thorough evaluation may be sufficient to identify many patients unlikely to benefit from cardiac investigation in the pre-HBOT setting. A clinical decision-making tool based on suggested low-risk and high-risk features is offered to guide the use of targeted cardiac investigation prior to HBOT., Competing Interests: The authors report no conflicts of interest in this work., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Due to their physiological similarities to humans, pigs are used as experimental models for ex vivo lung perfusion (EVLP). EVLP is a technique that perfuses lungs that are not suitable for transplantation via an extracorporeal circulation pump to improve their function and increase their viability. Existing EVLP protocols are differentiated by the type of perfusion solution and perfusion flow, which varies from 40%-100% of the estimated cardiac output (CO) according to the body surface area (BSA). Devices for measuring CO use simple physical principles and other mathematical models. Thermodilution in animal models continues to be the reference standard for estimating CO because of its simplicity and ease of reproduction. Therefore, the objective of this study was to reproduce the measurement of CO by thermodilution in pigs and compare its precision and accuracy with those obtained by the BSA, weight, and Fick's method, to establish perfusion flow during EVLP. In 23 pigs, a thermodilution catheter was placed in the right jugular vein, and the carotid artery on the same side was cannulated. Blood samples were obtained for gasometry, and CO was estimated by thermodilution, adjusted body surface area, Fick's principle, and per body weight. The CO obtained by the BSA was greater (p = 0.0001, ANOVA, Tukey) than that obtained by the other methods. We conclude that although the methods used in this study to estimate CO are reliable, there are significant differences between them; therefore, each method must be evaluated by the investigator to determine which meets the needs of the protocol.

Objectives: To compare agreement between echocardiography and regional impedance cardiography (RIC)-derived cardiac output (CO), and to construct indicative normative ranges of CO for gestational age groups., Design, Setting and Participants: Prospective cohort observational study performed in a tertiary centre in London, UK, including neonates born between 25 and 42 weeks' gestational age., Exposures: Neonates on the postnatal ward had 2 hours of RIC monitoring; neonates in intensive care had RIC monitoring for the first 72 hours, then weekly for 2 hours, with concomitant echocardiography measures., Main Outcomes and Measures: RIC was used to measure CO continuously. Statistical analyses were performed using R (V.4.2.2; R Core Team 2022). RIC-derived CO and echocardiography-derived CO were compared using Pearson's correlations and Bland-Altman analyses. Differences in RIC-derived CO between infants born extremely, very and late preterm were assessed using analyses of variance and mixed-effects modelling., Results: 127 neonates (22 extremely, 46 very, 29 late preterm and 30 term) were included. RIC and echocardiography-measured weight-adjusted CO were correlated (r=0.62, p<0.001) with a Bland-Altman bias of -31 mL/min/kg (limits of agreement -322 to 261 mL/min/kg). The RIC-derived CO fell over 12 hours, then increased until 72 hours after birth. The 72-hour weight-adjusted mean CO was higher in extremely preterm (424±158 mL/min/kg) compared with very (325±131 mL/min/kg, p<0.001) and late preterm (237±81 mL/min/kg, p<0.001) neonates; this difference disappeared by 2-3 weeks of age., Conclusions: RIC is valid for continuous, non-invasive CO measurement in neonates. Indicative normative CO ranges could help clinicians to make more informed haemodynamic management decisions, which should be explored in future studies., Trial Registration Number: NCT04064177., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients 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 (V̇O 2peak ), which is determined by the product of cardiac output (CO) and arteriovenous oxygen difference (a-vDO 2 ). While exercise training has been shown to improve V̇O 2peak 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., Methods: We 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 (I 2 ) 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., Discussion: While several studies have reported a positive effect of supervised exercise training on cardiorespiratory fitness, attempts to assess the underlying determinants of V̇O 2peak , CO, and a-vDO 2 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 Registration: PROSPERO CRD42022361485., (© 2024. The Author(s).)

Cardiovascular diseases can be an emerging complication in cystic fibrosis (CF), as the median life expectancy has improved considerably. The objective of this study was to compare vascular, hemodynamic parameters and arterial stiffness in adult CF patients with healthy participants pared by sex and age, and to assess the factors associated with arterial stiffness in the CF group. This is a cross-sectional observational study. The evaluation of cardiovascular parameters was performed non-invasively using Mobil-O-Graph. 36 individuals with CF and 35 controls were evaluated. The mean arterial pressure (96.71 ± 10.98 versus 88.61 ± 7.40 mmHg, p = 0.0005), cardiac output (4.86 ± 0.57 versus 4.48 ± 0.44 L/min, p = 0.002) and systolic volume (64.30 ± 11.91 versus 49.02 ± 9.31 ml, p < 0.0001) were significantly lower in the CF group. The heart rate was higher in the CF when compared to the control (77.18 ± 10.47 versus 93.56 ± 14.57 bpm, p < 0.0001). The augmentation index (AIx@75) was higher in the CF than control (29.94 ± 9.37 versus 16.52 ± 7.179%, p < 0.0001). In the multivariate model controlled by body mass index and Forced Expiratory Volume in the first second, central systolic blood pressure and reflection coefficient directly related to AIx@75. Negatively related to AIx@75 were age and systolic volume. The adjusted determination coefficient was 87.40%. Individuals with CF presented lower arterial blood pressures and changes in cardiac function with lower stroke volume and cardiac output. The AIx@75, an indirect index of arterial stiffness and direct index of left ventricular overload, is increased in this population. The subclinical findings suggest the need for earlier cardiovascular assessment in this population due to increased risks of cardiovascular disease., (© 2024. The Author(s).)

Background: Significant hemodynamic changes occur during liver transplantation, emphasizing the importance of precious and continuous monitoring of cardiac output, cardiac index, and other parameters. Although the monitoring of cardiac output by pulse indicator continuous cardiac output (PiCCO) was statistically homogeneous compared to the clinical gold standard pulmonary artery catheterization (PAC) in previous studies of liver transplantation, there are fewer statistical methods for the assessment of its conclusions, and a lack of comparisons of other hemodynamic parameters (e.g., SVRI, systemic vascular resistance index). Some studies have also concluded that the agreement between PiCCO and PAC is not good enough. Overall, there are no uniform conclusions regarding the agreement between PiCCO and PAC in previous studies. This study evaluates the agreement and trending ability of relevant hemodynamic parameters obtained with PiCCO compared to the clinical gold standard PAC from multiple perspectives, employing various statistical methods., Methods: Fifty-two liver transplantation patients were included. Cardiac output (CO), cardiac index (CI), SVRI and stroke volume index (SVI) values were monitored at eight time points using both PiCCO and PAC. The results were analyzed by Bland-Altman analysis, Passing-bablok regression, intra-class correlation coefficient (ICC), 4-quadrant plot, polar plot, and trend interchangeability method (TIM)., Results: The Bland-Altman analysis revealed high percentage errors for PiCCO: 54.06% for CO, 52.70% for CI, 62.18% for SVRI, and 51.97% for SVI, indicating poor accuracy. While Passing-Bablok plots showed favorable agreement for SVRI overall and during various phases, the agreement for other parameters was less satisfactory. The ICC results confirmed good overall agreement between the two devices across most parameters, except for SVRI during the new liver phase, which showed poor agreement. Additionally, four-quadrant and polar plot analyses indicated that all agreement rate values fell below the clinically acceptable threshold of over 90%, and all angular deviation values exceeded ± 5°, demonstrating that PiCCO is unable to meet the acceptable trends. Using the TIM, the interchangeability rates were found to be quite low: 20% for CO and CI, 16% for SVRI, and 13% for SVI., Conclusions: Our study revealed notable disparities in absolute values of CO, CI, SVRI and SVI between PiCCO and PAC in intraoperative liver transplant settings, notably during the neohepatic phase where errors were particularly pronounced. Consequently, these findings highlight the need for careful consideration of PiCCO's advantages and disadvantages in liver transplantation scenarios, including its multiple parameters (such as the encompassing extravascular lung water index), against its limited correlation with PAC., (© 2024. The Author(s).)

This study aimed to highlight the ventilatory and circulatory determinants of changes in ˙VO 2 peak after exercise-based cardiac rehabilitation (ECR) in patients with coronary heart disease (CHD). Eighty-two CHD patients performed, before and after a 3-month ECR, a cardiopulmonary exercise testing (CPET) on a bike with gas exchanges measurements (˙VO 2 peak, minute ventilation, i. e., ˙VE), and cardiac output (Q˙c). The arteriovenous difference in O 2 (C(a-v¯)O 2 ) and the alveolar capillary gradient in O 2 (PAi-aO 2 ) were calculated using Fick's laws. Oxygen uptake efficiency slope (OUES) was calculated. A 5.0% cut off was applied for differentiating non- (NR: ˙VO 2 <0.0%), low (LR: 0.0≤ ∆˙VO 2 <5.0%), moderate (MR: 5.0≤∆˙VO 2  < 10.0%), and high responders (HR: ∆˙VO 2 ≥10.0%) to ECR. A total of 44% of patients were HR (n=36), 20% MR (n=16), 23% LR (n=19), and 13% NR (n=11). For HR, the ˙VO 2 peak increase (p<0.01) was associated with increases in ˙VE (+12.8±13.0 L/min, p<0.01), (+1.0±0.9 L/min, p<0.01), and C(a-v¯)O 2 (+2.3±2.5 mLO 2 /100 mL, p<0.01). MR patients were characterized by+6.7±19.7 L/min increase in ˙VE (p=0.04) and+0.7±1.0 L/min of Q˙c (p<0.01). ECR induced decreases in ˙VE (p=0.04) and C(a-v¯)O 2 (p<0.01) and a Q˙c increase in LR and NR patients (p<0.01). Peripheral and ventilatory responses more than central adaptations could be responsible for the ˙VO 2 peak change with ECR in CHD patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Disclosures None.

Purpose of Review: To describe current and near future developments and applications of CO2 kinetics in clinical respiratory and cardiovascular monitoring., Recent Findings: In the last years, we have witnessed a renewed interest in CO2 kinetics in relation with a better understanding of volumetric capnography and its derived parameters. This together with technological advances and improved measurement systems have expanded the monitoring potential of CO2 kinetics including breath by breath continuous end-expiratory lung volume and continuous noninvasive cardiac output. Dead space has slowly been gaining relevance in clinical monitoring and prognostic evaluation. Easy to measure dead space surrogates such as the ventilatory ratio have demonstrated a strong prognostic value in patients with acute respiratory failure., Summary: The kinetics of carbon dioxide describe many relevant physiological processes. The clinical introduction of new ways of assessing respiratory and circulatory efficiency based on advanced analysis of CO2 kinetics are paving the road to a long-desired goal in clinical monitoring of critically ill patients: the integration of respiratory and circulatory monitoring during mechanical ventilation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Functional capacity remains limited in heart failure patients with left ventricular assist devices (LVADs) due to fixed pump speed and inability to offload the left ventricle adequately. We hypothesized that manually adjusting LVAD speed during exercise based on pulmonary capillary wedge pressures would increase total cardiac output and maximal oxygen consumption. Two participants with a HeartWare LVAD underwent an invasive ramp study at rest followed by an invasive cardiopulmonary stress test exercising in two randomized phases: fixed speed and adjusted speed. In the latter phase, speed was adjusted every 1 minute during exercise at ±20 rpm/1 mm Hg change from baseline pulmonary capillary wedge pressure. There was no difference in maximal oxygen consumption between the two phases, with a modest increase in total cardiac output during speed adjustment. Filling pressures were initially controlled during speed adjustment until speed was capped at 4,000 rpm, at which point filling pressures increased. Blood pressure was variable. The pressure across the head of the pump (ΔP) was higher with speed adjustment. Contrary to our hypothesis, LVAD speed adjustment during exercise did not improve total cardiac output and functional capacity. This variable response may be attributed to the native cardiac reserve and baroreceptor response; however, additional studies are needed., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Purpose: Oxygen delivery (DO 2 ) and its monitoring are highlighted to aid postoperative goal directed therapy (GDT) to improve perioperative outcomes such as acute kidney injury (AKI) after high-risk cardiac surgeries associated with multiple morbidities and mortality. However, DO 2 monitoring is neither routine nor done postoperatively, and current methods are invasive and only produce intermittent DO 2 trends. Hence, we proposed a novel algorithm that simultaneously integrates cardiac output (CO), hemoglobin (Hb) and oxygen saturation (SpO 2 ) from the Edwards Life Sciences ClearSight System® and Masimo SET Pulse CO-Oximetry® to produce a continuous, real-time DO 2 trend., Methods: Our algorithm was built systematically with 4 components - machine interface to draw data with PuTTY, data extraction with parsing, data synchronization, and real-time DO 2 presentation using a graphic-user interface. Hb readings were validated., Results: Our algorithm was implemented successfully in 93% (n = 57 out of 61) of our recruited cardiac surgical patients. DO 2 trends and AKI were studied., Conclusion: We demonstrated a novel proof-of-concept and feasibility of continuous, real-time, non-invasive DO 2 monitoring, with each patient serving as their own control. Our study also lays the foundation for future investigations aimed at identifying personalized critical DO 2 thresholds and optimizing DO 2 as an integral part of GDT to enhance outcomes in perioperative cardiac surgery., (© 2024. The Author(s).)