Agreement of cardiac index measurements between ultrasonic cardiac output monitor and transthoracic echocardiography in neonates.

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.

Association between right heart size and right ventricular output reserve in patients with pulmonary arterial hypertension.

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 cm2 at rest, and at 25 and 50 W (all p < 0.001) and for patients with enlarged RV area > 20 cm2 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.

Cardiovascular responses to experimental weight gain in humans: a feasibility study.

OBJECTIVE: Obesity and hypertension share a well known association. However, the mechanisms underlying their relationship are not well understood. Our goal was to assess the feasibility of a longitudinal, interventional weight gain study with detailed cardiovascular measurements in humans. METHODS: Sixteen healthy, normotensive, young, male volunteers (28 ±â€Š7 years) were enrolled. Body composition, biochemical and cardiovascular data were obtained at baseline, and after an 8-week period of overfeeding (800-1000 kcal/day). Blood pressure (BP), cardiac output (CO) and peripheral vascular resistance (PVR) were determined, as were the minimum forearm vascular resistance (MFVR), forearm blood flow (FBF) response to mental stress and heart rate variability (HRV) parameters. RESULTS: Overfeeding resulted in a median weight gain of 5.6 kg [interquartile range (IQR) 4.6-6.4 kg; P  < 0.001]. Seated systolic and diastolic BP were significantly increased by 10 ±â€Š9 and 4 ±â€Š6 mmHg, respectively, after weight gain ( P  < 0.001 and P  = 0.011, respectively). CO also increased and PVR decreased significantly as a result of weight gain ( P  = 0.032 and P  = 0.044, respectively). MFVR was also significantly decreased after weight gain ( P  = 0.023). The FBF response to mental stress was blunted significantly ( P  = 0.002), and sympathovagal balance and responsiveness to orthostatic challenge altered moderately after weight gain. CONCLUSION: Our overfeeding regimen resulted in moderate weight gain and significant increases in BP. An increase in CO is likely to be the dominant mechanism underlying the observed BP changes, with decreases in PVR partially compensating for these effects. Experimental weight gain, coupled with detailed cardiovascular phenotyping, is a feasible model to examine potential mechanisms underlying obesity-associated hypertension in young adults.

Plasma catecholamines in patients undergoing invasive cardiopulmonary exercise test for exercise intolerance.

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.

Evaluating tissue hypoxia and the response to fluid administration in septic shock patients: a metabolic cluster analysis.

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 (ScvO2), central venous-to-arterial carbon dioxide difference (PcvaCO2), and PcvaCO2 corrected by the difference in arterial-to-venous oxygen content (PcvaCO2/CavO2). RESULTS: Seventy-seven fluid challenges were analyzed. Cluster analysis revealed two distinct metabolic profiles at baseline. Cluster A exhibited lower ScvO2, higher PcvaCO2, and lower PcvaCO2/CavO2. Increases in cardiac output (CO) were associated with increases in VO2 exclusively in cluster A. Baseline isolated metabolic variables did not correlate with VO2 response, and changes in ScvO2 and PcvaCO2 were associated to VO2 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 VO2 might increase as results of fluid administration.

The relevance of vascular adjustments to hemodynamic control in the face of temperature change in Crotalus durissus.

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.

Effects of preterm birth on the pattern of altitude acclimatization at rest and during moderate-intensity exercise across three days at 3,375 m.

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.

Sprint interval training in the postpartum period maintains the enhanced cardiac output of pregnancy: A case study.

During pregnancy an increased cardiac output ( Q ̇ $\dot{Q}$ ) and blood volume (BV) occur to support fetal growth. Increased Q ̇ $\dot{Q}$ and BV also occur during chronic endurance exercise training and benefit performance. We investigated if sprint interval training (SIT) undertaken early postpartum maintains the elevated Q ̇ $\dot{Q}$ and BV of pregnancy and benefits performance. The participant, a competitive field hockey player and former cyclist, visited our laboratory at 2 weeks of gestation (baseline) and postpartum pre-, mid- and post-intervention (PPpre, PPmid and PPpost). Delivery was uncomplicated and she felt ready to start the SIT programme 5 weeks postpartum. Inert gas rebreathing was used to measure peak exercise Q ̇ $\dot{Q}$ ( Q ̇ $\dot{Q}$ peak); V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ was measured with a metabolic cart; and postpartum haematological values were measured with carbon monoxide rebreathing. The 18 SIT sessions progressed from four to eight sprints at 130% of V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ peak power output. Q ̇ $\dot{Q}$ peak increased from baseline at all postpartum time points (baseline 16.2 vs. 17.5, 16.8 and 17.2 L/min at PPpre, PPmid and PPpost, respectively). Relative V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ remained below baseline values at all postpartum measurements (baseline 44.9 vs. 41.0, 42.3 and 42.5 mL/kg/min at PPpre, PPmid and PPpost, respectively) whereas absolute V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ rapidly reached baseline values postpartum (baseline 3.19 vs. 3.12, 3.23 and 3.18 L/min at PPpre, PPmid and PPpost, respectively). Postpartum BV (5257, 4271 and 5214 mL at PPpre, PPmid and PPpost, respectively) and Hbmass (654, 525 and 641 g at PPpre, PPmid and PPpost, respectively) were similar between PPpre and PPpost but decreased alongside Q ̇ $\dot{Q}$ peak at PPmid. Peak power was returned to pre-pregnancy values by intervention end (302 vs. 303 W, baseline vs. PPpost). These findings show that SIT undertaken early postpartum defends the elevated Q ̇ $\dot{Q}$ peak of pregnancy and rapidly returns absolute V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ and peak power to baseline levels.

Long-term stress exposure, cortisol level and cardiovascular activity and reactivity: Observations in patients with fibromyalgia.

Previous research suggested that exposure to long-lasting or repeated laboratory stressors may lead to rearrangement of cardiovascular control, with a shift of regulation mechanisms from dominant cardiac to dominant vascular influences between the early and late response phases, respectively. This study investigated whether similar rearrangement occurs during life stress accompanying chronic disease by analyzing also associations between cortisol level and cardiovascular variables in patients with fibromyalgia (FM). In 47 women with FM and 36 healthy women (HW), cardiovascular recordings were taken during active body posture changes (sitting, lying down, and standing). Moreover, hair cortisol concentration (HCC) was obtained. During standing, which involved orthostatic challenge, FM patients showed higher total peripheral resistance (TPR) but lower stroke volume (SV), cardiac output (CO), and baroreflex sensitivity than HW. During sitting and lying down, TPR was more closely associated with blood pressure (BP) than CO in FM patients; in contrast, CO was more closely associated with BP than TPR in HW. HCC correlated positively with TPR and BP in FM patients, but negatively with TPR and BP and positively with SV and CO in HW. Results suggest that chronic disease-related stress is associated with alterations in cardiovascular regulation toward greater involvement of vascular than cardiac mechanisms in BP control. Stress-related cortisol release may contribute to the long-term rearrangement of autonomic regulation. At the behavioral level, the dominance of vascular over cardiovascular control may relate to reduced somatic mobilization during an active fight-flight response in favor of passive and behaviorally immobile coping.

Assessing Leg Blood Flow and Cardiac Output During Running Using Thermodilution.

Cardiac output (Q̇C) and leg blood flow (Q̇LEG) 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 Q̇LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇LEG 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. Q̇LEG and Q̇C 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 (V̇O2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇LEG (19.0 vs. 19.5 L/min) and Q̇C (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% V̇O2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O2peak). In summary, we present the first direct measure of Q̇LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.

Absolute values of regional ventilation-perfusion mismatch in patients with ARDS monitored by electrical impedance tomography and the role of dead space and shunt compensation.

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 ' /QSHUNT) 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 (QND/ 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 PaO2/FiO2 (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.

Determination of Cardiac Output in a Porcine Model for Ex Vivo Pulmonary Perfusion.

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.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

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 H2FPEF (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.

The role of the heart in the evolution of aerobic performance.

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.

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

BACKGROUND: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation. METHODS: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO2) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO2 slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO2, and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity. RESULTS: Peak VO2 during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P=0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO2/dL blood; P<0.001). During single leg knee extension, there was no difference in peak leg VO2 (P=0.306), but the peripherally limited group had greater blood flow/VO2 ratio (P=0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO2/dL blood; P=0.013), and lower muscle oxygen diffusive conductance (P=0.021). A difference in magnetic resonance spectroscopy-derived phosphocreatine recovery time was not detected (P=0.199). CONCLUSIONS: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O2 ratio and poor muscle diffusive capacity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844.

The prognostic relevance of exercise pulmonary hypertension in cardiac and pulmonary diseases.

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.

Effect of Hemodynamic Monitoring Systems on Short-Term Outcomes after Living Donor Liver Transplantation.

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.

Changes in oxygen supply-demand balance during induction of general anesthesia: an exploratory study using remimazolam.

PURPOSE: This study was performed to evaluate the changes in oxygen supply-demand balance during induction of general anesthesia using an indirect calorimeter capable of measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). METHODS: This study included patients scheduled for surgery in whom remimazolam was administered as a general anesthetic. VO2 and VCO2 were measured at different intervals: upon awakening (T1), 15 min after tracheal intubation (T2), and 1 h after T2 (T3). Oxygen delivery (DO2) was calculated simultaneously with these measurements. VO2 was ascertained using an indirect calorimeter and further calculated using vital signs, among other factors. DO2 was derived from cardiac output and arterial blood gas analysis performed with an arterial pressure-based cardiac output measurement system. RESULTS: VO2, VCO2, and DO2 decreased significantly from T1 to T2 and T3 [VO2/body surface area (BSA) (ml/min/m2): T1, 130 (122-146); T2, 107 (83-139); T3, 97 (93-121); p = 0.011], [VCO2/BSA (ml/min/m2): T1, 115 (105-129); T2, 90 (71-107); T3, 81 (69-101); p = 0.011], [DO2/BSA (ml/min/m2): T1, 467 (395-582); T2, 347 (286-392); T3, 382 (238-414); p = 0.0020]. Among the study subjects, a subset exhibited minimal reduction in VCO2. Although the respiratory frequency was titrated on the basis of end-tidal CO2 levels, there was no significant difference between the groups. CONCLUSION: General anesthetic induction with remimazolam decreased VO2, VCO2, and DO2.

The role of routine cardiac investigations before hyperbaric oxygen treatment.

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.