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Altered gravity environments introduce cardiovascular changes that may require continuous hemodynamic monitoring in both spaceflight and terrestrial analogs. Conditions in such environments are often prohibitive to direct/invasive methods and therefore, indirect measurement techniques must be used. This study compares two common cardiac measurement techniques used in the human spaceflight domain, pulse contour analysis (PCA—Nexfin) and inert gas rebreathing (IGR—Innocor), in subjects completing ergometer exercise under altered gravity conditions simulated using a tilt paradigm. Seven subjects were tilted to three different angles representing Martian, Lunar, and microgravity conditions in the rostrocaudal direction. They completed a 36-min submaximal cardiovascular exercise protocol in each condition. Hemodynamics were continuously monitored using Nexfin and Innocor. Linear mixed-effects models revealed a significant bias of $$25.7\pm 1.7$$ ml ( $$p

Sprint interval training (SIT), characterized by brief bouts of ‘supramaximal’ exercise interspersed with recovery periods, increases peak oxygen uptake ( $${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ ) despite a low total exercise volume. Per the Fick principle, increased $${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ is attributable to increased peak cardiac output ( $${\dot{{Q}}}_{\text{peak}} $$ ) and/or peak arterio-venous oxygen difference (a-vO2diff). There are limited and equivocal data regarding the physiological basis for SIT-induced increases in $${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ , with most studies lasting ≤ 6 weeks. To determine the effect of 12 weeks of SIT on $${\dot{{Q}}}_{\text{peak}} $$ , measured using inert gas rebreathing, and the relationship between changes in $${\dot{{Q}}}_{\text{peak}} $$ and $${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ . 15 healthy untrained adults [6 males, 9 females; 21 ± 2 y (mean ± SD)] performed 28 ± 3 training sessions. Each session involved a 2-min warm-up at 50 W, 3 × 20-s ‘all-out’ cycling bouts (581 ± 221 W) interspersed with 2-min of recovery, and a 3-min cool-down at 50 W. Measurements performed before and after training showed that 12 weeks of SIT increased $${\dot{{Q}}}_{\text{peak}} $$ (17.0 ± 3.7 vs 18.1 ± 4.6 L/min, p = 0.01, partial η2 = 0.28) and $${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ (2.63 ± 0.78 vs 3.18 ± 1.1 L/min, p

Objective The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD). Methods and Results Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4 ± 0.9 L/min vs 4.7 ± 0.8 L/min, P = .27) or patients with heart failure (4.4 ± 1.4 L/min vs 4.5 ± 1.3 L/min, P = .75). There was a strong relationship between thermodilution and IGR cardiac index (r = 0.81, P = .001) and stroke volume index (r = 0.75, P = .001). Bland–Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR, namely, the mean difference (lower and upper limits of agreement) for patients with heart failure –0.002 L/min/m2 (–0.65 to 0.66 L/min/m2), and –0.14 L/min/m2 (–0.78 to 0.49 L/min/m2) for patients with LVAD. Conclusions IGR is a valid method for estimating cardiac output and should be used in clinical practice to complement the evaluation and management of chronic heart failure and patients with an LVAD.

Background Inert gas rebreathing has been recently described as an emergent reliable non-invasive method for cardiac output determination during exercise, allowing a relevant improvement of cardiopulmonary exercise test clinical relevance. For cardiac output measurements by inert gas rebreathing, specific respiratory manoeuvres are needed which might affect pivotal cardiopulmonary exercise test parameters, such as exercise tolerance, oxygen uptake and ventilation vs carbon dioxide output (VE/VCO2) relationship slope. Method We retrospectively analysed cardiopulmonary exercise testing of 181 heart failure patients who underwent both cardiopulmonary exercise testing and cardiopulmonary exercise test+cardiac output within two months (average 16 ± 15 days). All patients were in stable clinical conditions (New York Heart Association I–III) and on optimal medical therapy. Results The majority of patients were in New York Heart Association Class I and II (78.8%), with a mean left ventricular ejection fraction of 31 ± 10%. No difference was found between the two tests in oxygen uptake at peak exercise (1101 (interquartile range 870–1418) ml/min at cardiopulmonary exercise test vs 1103 (844–1389) at cardiopulmonary exercise test-cardiac output) and at anaerobic threshold. However, anaerobic threshold and peak heart rate, peak workload (75 (58–101) watts and 64 (42–90), p 2 slope was higher at cardiopulmonary exercise test+cardiac output (30 (27–35) vs 33 (28–37), p Conclusion The similar anaerobic threshold and peak oxygen uptake in the two tests with a lower peak workload and higher VE/VCO2 slope at cardiopulmonary exercise test+cardiac output suggest a higher respiratory work and consequent demand for respiratory muscle blood flow secondary to the ventilatory manoeuvres. Accordingly, VE/VCO2 slope and peak workload must be evaluated with caution during cardiopulmonary exercise test+cardiac output.

The aim of this study was to evaluate an inert gas rebreathing method (Innocor) for measurement of cardiac output and related haemodynamic variables and to provide robust normative data describing the influence of age, gender and body size on these variables. Four separate studies were conducted: measurement repeatability (study 1, n = 45); postural change (study 2, n = 40); response to submaximal cycling exercise (study 3, n = 20); and the influence of age, gender and body size (study 4, n = 1400). Repeated measurements of cardiac output, stroke volume and heart rate were similar, with low mean (±SD) differences (0.26 ± 0.53 L/min, 0 ± 11 mL and 2 ± 6beats/min, respectively). In addition, cardiac output and stroke volume both declined progressively from supine to seated and standing positions (P P P P

Funder: Cambridge NIHR cardiorespiratory BRC, This investigation validated the inert gas rebreathing (IGR) technique and determined IGR prognostic ability compared to invasive cardiac output measurements in patients with pulmonary hypertension. IGR compared with thermodilution cardiac output demonstrated a moderate bias. IGR technique demonstrated long-term prognostic value comparable to invasive cardiac output in pulmonary hypertension patients.

There are many complex cardiac malformations that are characterized by a functionally univentricular physiology. Staged surgical repair according to the Fontan principle separates the systemic and pulmonary circulations by connecting the systemic venous return to the pulmonary arteries. However, long-term follow-up studies demonstrate a gradual deterioration of cardiac function, particularly from the second or third decade. Noninvasive evaluation of the cardiac function is, therefore, important in the follow-up of these patients. The cardiac index (CI) is a reliable hemodynamic parameter and represents an important marker of cardiac function. We compared CI values determined by cardiac MRI (CMRI) with values obtained by noninvasive inert gas rebreathing (IGR; Innocor® system). Sixteen patients (age range: 7.2–32.7 years) with functionally univentricular hearts (UVH) following total cavopulmonary connection (TCPC) were compared with 12 healthy subjects (age range: 8.5–18.6 years). The standard treadmill protocol of the German Society of Pediatric Cardiology was used for exercise testing. CI was determined at rest and at two standardized submaximal exercise levels. In all subjects, CI increased under exercise conditions, but the values were significantly lower in patients with UVH. There was no significant difference between patients with UVH and predominantly right- or left-ventricular morphology. In comparison with CMRI measurements, the CI values obtained by the IGR method tended to be lower, with a mean difference of 1.02 l/min/m2. Noninvasive measurement of CI with the IGR method is feasible at rest and during exercise, and appears to be suited for routine determination of CI in patients with UVH following TCPC.

Extracellular matrix (ECM) biomarkers such as matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are pathophysiological key, prognostic marker and therapeutic target in chronic heart failure (HF). Serial measurements of MMPs and TIMPs may be useful for guidance of these applications. However, interpretation of time-dependent changes requires knowledge about the biological variation of ECM biomarkers. We performed measurements of MMP-2, MMP-9, TIMP-1, and TIMP-4 in 50 patients with chronic HF who met rigid criteria for clinical stability at 3-h, 6-h, 1-week and 2-week time intervals. In addition, clinical and haemodynamic assessment was performed at baseline, at 1- and 2-week intervals. Haemodynamic variables were measured using inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with external ECG event recorders throughout the complete study. Reference change values (RCVs) and minimal important differences (MIDs) were determined for MMP-2, MMP-9, TIMP-1, and TIMP-4. Clinical and haemodynamic variables were stable over time. Depending on the time-interval, RCVs ranged between 4.9 and 11.7% for MMP-2, 26.4 and 56.7% for MMP-9, 10.8 and 30.7% for TIMP-1, and 16.0 and 47.4% for TIMP-4, respectively. The MIDs varied between 43.38 and 65.22 ng/ml for MMP-2, 28.71 and 40.96 ng/ml for MMP-9, 52.32 and 156.07 ng/ml for TIMP-1, and 293.92 and 798.04 pg/ml for TIMP-4, respectively. The biological variation of ECM biomarkers differs with respect to individual biomarkers and time intervals. MMP-2 may be most suitable for serial biomarker measurements, as the biological variation is low irrespective of the time interval between measurements.

SummaryPurpose This study assessed the agreement between cardiac output estimated by inert gas rebreathing and bioreactance methods at rest and during exercise. Methods Haemodynamic measurements were assessed in 20 healthy individuals (11 females, nine males; aged 32 ± 10 years) using inert gas rebreathing and bioreactance methods. Gas exchange and haemodynamic data were measured simultaneously under rest and different stages (i.e. 30, 60, 90, 120, 150 and 180 W) of progressive graded cardiopulmonary exercise stress testing using a bicycle ergometer. Results At rest, bioreactance produced significantly higher cardiac output values than inert gas rebreathing (7·8 ± 1·4 versus 6·5 ± 1·7 l min−1, P = 0·01). At low-to-moderate exercise intensities (i.e. 30–90 W), bioreactance produced significantly higher cardiac outputs compared with rebreathing method (P

The aim of this study was to evaluate an inert gas rebreathing method (Innocor) for measurement of cardiac output and related haemodynamic variables and to provide robust normative data describing the influence of age, gender and body size on these variables. Four separate studies were conducted: measurement repeatability (study 1, n = 45); postural change (study 2, n = 40); response to submaximal cycling exercise (study 3, n = 20); and the influence of age, gender and body size (study 4, n = 1400). Repeated measurements of cardiac output, stroke volume and heart rate were similar, with low mean (±SD) differences (0.26 ± 0.53 L/min, 0 ± 11 mL and 2 ± 6beats/min, respectively). In addition, cardiac output and stroke volume both declined progressively from supine to seated and standing positions (P < 0.001 for both) and there was a stepwise increase in both parameters moving from rest to submaximal exercise (P < 0.001 for both). In study 4, there was a significant age-related decline in cardiac output and stroke volume in males and females, which remained significant after adjusting for body surface area (BSA, P < 0.001 for all comparisons). Both parameters were also significantly higher in those with high body mass index (BMI; P < 0.01 versus those with normal BMI for all comparisons), although indexing cardiac output and stroke volume to BSA reversed these trends. Inert gas rebreathing using the Innocor device provides repeatable measurements of cardiac output and related indices, which are sensitive to the effects of acute physiological manoeuvres. Moreover, inert gas rebreathing is a suitable technique for examining chronic influences such as age, gender and body size on key haemodynamic components of the arterial blood pressure.

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23–32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min−1, p=0.54; 114 (28) vs. 108 (15) ml beat−1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p

In some clinical and/or research settings, it is helpful to incorporate additional technologies and modalities into the standard cardiopulmonary exercise test. This chapter discusses some of them, including exercise flow-volume loops, measurement of cardiac output (invasive and noninvasive), blood sampling during exercise, and exercise oscillatory ventilation.

We measured cardiac output ( $$\dot {Q}$$ ) during sub-maximal and supra-maximal exercise with inert gas rebreathing ( $${\dot {Q}_{{\text{IN}}}}$$ ) and modified cardio-impedance ( $${\dot {Q}_{{\text{PF}}}}$$ ) and we evaluated the repeatability of the two methods. $$\dot {V}$$ O2 and $$\dot {Q}$$ were measured twice in parallel with the two methods at sub-maximal (50–250 W) and supra-maximal exercise in 7 young subjects (25 ± 1 years; 74.4 ± 5.2 kg; 1.84 ± 0.07 m). $${\dot {Q}_{{\text{IN}}}}$$ and $${\dot {Q}_{{\text{PF}}}}$$ increased by 3.4 L·min−1 and by 5.1 L·min−1 per 1 L·min−1 of increase in $$\dot {V}{{\text{O}}_{\text{2}}}$$ , respectively. Mean $${\dot {Q}_{{\text{PF}}}}$$ (23.3 ± 2.5 L·min−1) was 9% lower than $${\dot {Q}_{{\text{IN}}}}$$ (25.8 ± 2.2 L·min−1) during supra-maximal exercise. Bland–Altman analysis showed that: (i) bias ( $${\dot {Q}_{{\text{PF}}}}$$ – $${\dot {Q}_{{\text{IN}}}}$$ ) was significantly different from zero (− 0.65 ± 2.61 L·min−1) and; (ii) the ratios $${\dot {Q}_{{\text{PF}}}}$$ ÷ $${\dot {Q}_{{\text{IN}}}}$$ were linearly related with $$\dot {Q}$$ , indicating that $${\dot {Q}_{{\text{IN}}}}$$ tended to overestimate $$\dot {Q}$$ in comparison with $${\dot {Q}_{{\text{PF}}}}$$ for values ranging from 10.0 to 15.0 L·min−1 and to underestimate it for larger values. The coefficient of variation was similar for sub-maximal values (8.6% vs. 7.7%; 95% CL: ×/÷1.31), but lower for $${\dot {Q}_{{\text{PF}}}}$$ (7.6%; 95% CL: ×/÷ 2.05) than for $${\dot {Q}_{{\text{IN}}}}$$ (27.7%; 95% CL: ×/÷2.54) at supra-maximal intensity. $${\dot {Q}_{{\text{PF}}}}$$ seems to represent a valuable alternative to invasive methods for assessing $$\dot {Q}$$ during sub-maximal exercise. The $${\dot {Q}_{{\text{PF}}}}$$ underestimation with respect to $${\dot {Q}_{{\text{IN}}}}$$ during supra-maximal exercise suggests that $${\dot {Q}_{{\text{PF}}}}$$ might be less optimal for supra-maximal intensities.

In the course of time implantation of left ventricular assist devices (LVAD) has become an alternative to heart transplantation due to the enormous technical developments and miniaturization of these systems. Following implantation most patients show a significant improvement in their clinical condition and exercise capacity as measured by the New York Heart Association (NYHA) classification; nevertheless, exercise tolerance remains clearly limited even after LVAD implantation. The complex physiological and hemodynamic changes in LVAD patients both at rest and during exercise are ultimately not completely understood. The aim of this article is to describe the current state of scientific knowledge with respect to the physical capacity of patients with terminal heart failure after LVAD implantation at rest and during exercise. The influence of increasing the pump speed and continuous physical exercise training on the physical capacity in the long-term course is reviewed. The significance of new diagnostic tools, such as the non-invasive inert gas rebreathing method for measurement of cardiac output and arteriovenous oxygen difference (AVDO2) in assessment of the performance of LVAD patients is discussed.

In patients with left ventricular assist devices (LVAD), exercise capacity is a decisive factor regarding the quality of life. When evaluating exercise capacity, precise information about the total cardiac output generated is crucial. To date, complex measurements using a right-heart catheter were necessary in order to determine total cardiac output. The inert gas rebreathing method facilitates non-invasive, direct and valid measurement of total cardiac output as well as associated parameters, like the difference in arteriovenous oxygen saturation, both at rest and during exercise. It is the aim of this paper to focus on this conclusive method which is, despite its simplicity and low-risk reproducibility, rarely used within the framework of LVAD patient treatment at the present time. The test protocol used at our hospital is presented to facilitate the implementation of this helpful tool in other interested institutions.

Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2 = 12%). While all four methods reported a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0.001] and hypoxia (7.2 ± 0.7, 4.9 ± 0.5, 6.4 ± 0.8 and 5.1 ± 0.4 L/min per L/min; P = 0.04). In hypoxia, the increase in the Q/VO2 slope was not detected by Nexfin. In normoxia, Q increases by 5-6 L/min per L/min increase in VO2, which is within the 95% confidence interval of the Q/VO2 slopes determined by the modified Fick method, Physioflow, and Nexfin apparatus while Innocor provided a lower value, potentially reflecting recirculation of the test gas into the pulmonary circulation. Thus, determination of Q during exercise depends significantly on the applied method.

Over time left ventricular assist devices (LVAD) have become an alternative to heart transplantation because of enormous technical development and miniaturization. Most patients present a significant improvement in clinical conditions and exercise capacity. Nevertheless, exercise tolerance remains markedly limited even after LVAD implantation compared to a control group. The complex physiological and hemodynamic changes in LVAD patients, both at rest and during exercise, are not yet understood, or at least not completely. It is the aim of the present paper to describe the current state of scientific knowledge. Furthermore, the spectrum of diagnostic tools, including the noninvasive inert gas rebreathing method for measurement of cardiac output and associate parameters, are discussed. Options for training control in this special patient group are presented.

Exercise performance improvement after training in heart failure (HF) can be due to central or peripheral changes.In 70 HF stable patients we measured peak VO(2) and cardiac output (CO, inert gas rebreathing technique) and calculated arteriovenous O(2) differences (a-v O(2)diff) before and after an 8-week training program. Peak VO(2) changed from 1111 ± 403 mL/minute to 1191 ± 441 (P.001), peak workload from 68 ± 29 watts to 76 ± 32 (P.0001), peakCO from 6.6 ± 2.2 L/minute to 7.3 ± 2.5 (P.0001), and peak a-v O(2)diff from 17.5 ± 5.1 mL/100 mL to 16.6 ± 4.1 (P = .081). Changes in peak CO and a-v O(2)diff allowed to identify 4 behaviors: group 1: (n = 15) reduction in peak CO and increase in a-v O(2)diff (peak VO(2) unchanged, peak workload +9.5%); group 2: (n = 16) both peak CO and a-v O(2)diff increased as well as peak VO(2) (23%) and workload (18%); group 3: (n = 4) peak CO and a-v O(2)diff reduced as well as peak VO(2) (-18%) and workload (-5%); group 4: (n = 35) peak CO increased with a-v O(2)diff reduced (increase in peak VO(2) by 5.5 and workload by 8.4%).Exercise training improves peakVO(2) by increasing CO with unchanged a-v O(2)diff. A reduction after training of a-v O(2)diff with an increase in CO is frequent (50% of cases), is suggestive of blood flow redistribution and, per se, not a sign of reduced muscle performance been associated with improved exercise capacity.

Exercise testing is often used to assess cardiac function during physical exertion to obtain diagnostic information. However, this procedure is limited to measuring the electrical activity of the heart using electrocardiography and intermittent blood pressure (BP) measurements and does not involve the continuous assessment of heart functioning. In this study, we compared continuous beat-to-beat pulse contour analysis to monitor noninvasive cardiac output (CO) during exercise with inert gas rebreathing and respired gas analysis. Nineteen healthy male volunteers were subjected to bicycle ergometry testing with increasing workloads. Cardiac output was deter- mined noninvasively by continuous beat-to-beat pulse contour analysis (Nexfin) and by inert gas rebreathing, and estimated using the respired gas analysis method. The effects of the rebreathing maneuver on heart rate (HR), stroke volume (SV), and CO were evaluated. The CO values derived from the Nexfin- and inert gas rebreathing methods were well correlated (r = 0.88, P < 0.01) and the limits of agreement were 30.3% with a measurement bias of 0.4 ± 1.8 L/min. Nexfin- and respired gas analysis-derived CO values correlated even better (r = 0.94, P < 0.01) and the limits of agreement were 21.5% with a measurement bias of -0.70 ± 1.6 L/min. At rest, the rebreathing maneuver increased HR by 13 beats/min (P < 0.01), SV remained unaffected (P = 0.7), while CO increased by 1.0 L/min (P < 0.01). Rebreathing did not affect these parameters during exercise. Nexfin continuous beat-to-beat pulse contour analysis is an appropriate method for noninvasive assessment of CO during exercise

Aims It is not clear whether cardiac resynchronization therapy (CRT) should only be optimized at rest or whether it is necessary to perform CRT optimization during exercise. Our study aims to answer this question by using an inert gas rebreathing method (Innocor®). Methods and results Twenty-seven patients with congestive heart failure and implanted CRT devices were included in the study. The aetiology of the heart failure was ischaemic in nine (33%) patients. Patients had low left ventricular ejection fraction (29 ± 8%) and enlarged LV end-diastolic diameters (63 ± 7 mm). Atrioventricular delay (AVD) was optimized at rest according to cardiac index (CI), measured by inert gas rebreathing (Innocor®). Thereafter, patients performed standardized, steady-state bicycle exercise at 30 W in sitting body position. Three AVDs were tested during exercise in a random sequence: optimized resting AVD (AVDopt) according to baseline measurement; AVDopt − 30 ms; and AVDopt + 30 ms. Cardiac index was measured in each AVD by inert gas rebreathing. Cardiac index increased significantly during exercise. However, neither AVDopt shortening nor prolongation during exercise had significant effect on CI (shortening of AVDopt − 30 ms was accompanied by a reduction of CI of 4.8%, prolongation of AVDopt + 30 ms was accompanied by a reduction of CI of 7.7%). Conclusion Shortening or lengthening of the AVD during exercise has no impact on CI in CRT patients. On the basis of our results, we conclude that in CRT patients the AVD should be programmed, fixed even during exercise.

Atrial fibrillation (AF) is associated with significant morbidity and mortality. To test the effect of interventions, knowledge of cardiac output (CO) is important. However, the irregular heart rate might cause some methods for determination of CO to have inherent weaknesses. Objective. To assess the validity of these methods in AF, a new inert gas rebreathing device and impedance cardiography was tested with echocardiography as reference.Using a cross-sectional design, 127 patients with AF and 24 in SR were consecutively recruited. Resting CO was measured using inert gas rebreathing (n = 62) or impedance measurement of intrathoracic blood flow (n = 89) in separate studies with echocardiographic measurement as reference.CO determined with impedance cardiography was mean 4.77 L/min ± 2.24(SD) compared to 4.93 L/min ± 1.17 by echocardiography (n = 89, n.s.) in patients with AF. CO by inert gas rebreathing was 4.98 L/min ± 2.49(SD) compared to 5.70 L/min ± 2.49 by echocardiography (n = 62, n.s.) in patients with AF and SR (AF 5.42 ± 2.9 vs. 6.27, n.s. and SR 4.09 ± 1.08 vs. 4.35 ± 0.86, n.s.). Mean bias between impedance cardiography and echocardiography was 0.14 ± 0.95 L/min and -0.13 ± 0.98 L/min between inert gas rebreathing and echocardiography. Inert gas rebreathing showed larger intra-patient variation than impedance cardiography (0.11 vs. 0.054). Correlation between inert gas rebreathing and echocardiography was r = -0.060 and between impedance cardiography and echocardiography was r = 0.128. Impedance cardiography and inert gas rebreathing both underestimated CO compared to echocardiography.Variation between the inert gas rebreathing and the reference method for AF patients was less than desired. Impedance cardiography was superior to inert gas rebreathing and showed acceptable agreement with echocardiography and variability similar to echocardiography.

Summary Objective: Right ventricular function determines the prognosis of pulmonary hypertension (PAH). Measurement of stroke volume (SV) non-invasively could be a promising method to monitor disease progression. Cardiac magnetic resonance (CMR) imaging is recognized as an accurate and reproducible method to measure SV. Inert gas rebreathing (IGR) using acetylene is a validated but cumbersome method for pulmonary blood flow (PBF) measurement in PAH. A more convenient rebreathing technique using rapid photoacoustic analysis of nitrous oxide has been introduced and validated in left heart failure. We investigated the accuracy of CMR imaging and IGR using photoacoustic analysis to measure SV in patients under investigation for PAH. Methods: Thirty-three patients (16♀:17♂) with suspected PAH following echocardiography had SV measured by CMR imaging (using pulmonary arterial{CMR PA} and aortic {CMR Ao} flow methods) and IGR. The results were compared with our reference standard: thermodilution (TD) measured during right heart catheterization (RHC). Results: All methods showed similar correlation for SV. Bland–Altman analysis con-firmed acceptable levels of agreement between the four techniques. TD versus CMR Ao flow had bias (limits of agreement) of −5·41 ml (−22·37 to 11·56 ml), TD versus CMR PA flow 0·12 ml (−20·13 to 20·37 ml) and TD versus IGR 6·25ml (−16·01 to 28·51 ml). Conclusion: Cardiac magnetic resonance imaging and IGR using photoacoustic analysis in patients with suspected PAH provided non-invasive measurements of SV that agreed closely with those obtained from TD measured during RHC.

Background: Many invasive and noninvasive methods have been proposed for guiding optimal programming of cardiac resynchronization therapy (CRT) devices. However, results are not satisfying. Preliminary results suggest that cardiac output (CO) measurements using inert gas rebreathing (IGR) might be an eligible method to tailor atrioventricular (AV) and ventriculo-ventricular (VV) programming. The aims of the present study were: (1) to evaluate whether an optimization of CRT can be obtained by noninvasive CO measurements and (2) to evaluate whether acute hemodynamic improvements obtained by this approach relate into increase in cardiac exercise capacity. Methods: In 24 patients on CRT, iterative VV- and AV-delay optimization was done using the IGR method. This blinded, randomized, crossover study compared the responses to optimization during two periods: a 4-week optimized and a 4-week standard programming. Exercise capacity after optimization was assessed after each period by New York Heart Association (NYHA) classification, a 6-minute walking test, and quality of life (QoL) questionnaire. Results: CO could be determined by IGR in all patients. The NYHA class decreased by 17.8% (2.8 ± 0.3 vs 2.3 ± 0.4, P < 0.001), the mean (± standard deviation) distance walked in 6 minutes was 9.3% greater after optimization (456 ± 140 m vs 417 ± 134 m, P < 0.001), and the QoL improved by 14.5% (41.8 ± 10.4 vs 36.5 ± 9.5, P < 0.001). The portion of responders to CRT increased from 66.5% to 87.5%. Conclusion: CRT optimization by iterative CO measurements leads to an increase in CO and an improvement of exercise capacity. Our results suggest that this method might become an important additive tool to adjust CRT programming. (PACE 2010; 33:1188–1194)

Objectives: Atrial fibrillation (AF) is one of the most frequent heart rhythm disorders. It potentially influences cardiac function and its measurement. Cardiac magnetic resonance imaging (CMR) has become the new gold standard for non-invasive assessment of cardiac output (CO). A novel inert gas rebreathing (IGR) device based on the Fick Principle also proved promising in patients in sinus rhythm (SR). The aim of our study was to compare the agreement of non-invasive CO measurements between CMR and IGR in AF patients. Methods: A total of 68 patients, 34 with AF and 34 pair-matched controls in SR, were included. Results: Bland-Altman analysis showed good agreement between both methods, with an average deviation of 0.2 ±1.2 l/min in the AF group versus 0.3 ±1.0 l/min in the SR group (p = 0.77). IGR demonstrated good agreement for CO between 2.0 and 5.4 l/min. However, in hyperdynamic circulatory conditions (CO >5.5 l/min), the increasing disagreement of IGR and CMR measurements reached statistical significance. Conclusions: Non-invasive CO measurements using CMR and IGR are feasible in patients suffering from AF. Good agreement was found between the two methods in an unselected cohort. Hyperdynamic circulatory conditions can lead to significant measurement differences which, however, do not affect the reproducibility of IGR.

The standard venous admixture formula is widely used in the bedside assessment of intrapulmonary shunt in intensive care units. The intrapulmonary shunt fraction calculated by the standard venous admixture formula is affected by the systemic oxygen extraction ratio and thus reflects both systemic and intrapulmonary shunts, especially in septic patients with decreased oxygen extraction ratios. The standard venous admixture formula may cause misestimation of the intrapulmonary shunt fraction, especially in septic patients. Inert gas rebreathing techniques and simultaneous measurement of cardiac output by thermodilution and oxygen consumption by indirect calorimetry may be useful in septic patients.

Background Cardiac Output (CO) is an important parameter in the diagnosis and therapy of heart diseases. Inert gas rebreathing (IGR) and continuous wave Doppler ultrasound (CWD) are among the most promising newer techniques aiming at a non-invasive, point of care measurement of CO. A direct comparison of the two methods has not yet been carried out. Methods 63 consecutive patients were included in the study. CO was measured twice with both CWD and IGR to assess inter-method agreement and reproducibility. The statistical comparisons were performed as proposed by Bland and Altman. Results There was a significant correlation between the CO measurements by both methods ( r =0.53, p p =0.13). Conclusion The determination of CO by IGR and CWD revealed a good agreement and reproducibility with a low rate of impossible measurements, suggesting that IGR and CWD can be used interchangeably in the clinical setting.

Background: The importance of noninvasive health monitoring in space increased as a result of the long-duration missions on the International Space Station (ISS). In order to monitor changes in cardiovascular indices such as cardiac output (CO) and total peripheral resistance (TPR), many methods have been developed using signal processing and mathematical modeling techniques. However, their performance in various gravitational conditions has not been known. Methods: The present study compared 10 methods to estimate CO and TPR by processing peripheral arterial blood pressure signals recorded from 8 subjects in multiple gravity levels (1 G, 0 G, and 1.8 G) during parabolic fl ights. For reference data sets, CO and TPR were simultaneously obtained by an inert gas rebreathing technique. Root normalized mean square errors and Bland-Altman plots were used to evaluate the estimation methods. Results: The corrected impedance method achieved the lowest estimation errors (20.0% CO error and 23.5% TPR error) over the three gravity levels. In microgravity, mean arterial pressure was also demonstrated to be an indicator of CO (24.5% error). Discussion: The corrected impedance method achieved low estimation errors for a wide range of the gravity levels. Gravity-dependent performance was observed in the mean arterial pressure method that achieved low errors in the shortterm 0 G.

The objective of this study was to evaluate inert gas rebreathing (IGR) reliability in cardiac output (CO) measurement compared with Fick method and thermodilution. IGR is a noninvasive method for CO measurement; CO by IGR is calculated as pulmonary blood flow plus intrapulmonary shunt. IGR may be ideal for follow-up of patients with pulmonary hypertension (PH), sparing the need of repeated invasive right-sided cardiac catheterization. Right-sided cardiac catheterization with CO measurement by thermodilution, Fick method, and IGR was performed in 125 patients with possible PH by echocardiography. Patients were grouped according to right-sided cardiac catheterization–measured mean pulmonary and wedge pressures: normal pulmonary arterial pressure (n = 20, mean pulmonary arterial pressure = 18 ± 3 mm Hg, pulmonary capillary wedge pressure = 11 ± 5 mm Hg), PH and normal pulmonary capillary wedge pressure (PH-NW, n = 37 mean pulmonary arterial pressure = 42 ± 13 mm Hg, pulmonary capillary wedge pressure = 11 ± 6 mm Hg), and PH and high pulmonary capillary wedge pressure (PH-HW, n = 68, mean pulmonary arterial pressure = 37 ± 9 mm Hg, pulmonary capillary wedge pressure = 24 ± 6 mm Hg). Thermodilution and Fick measurements were comparable. Fick and IGR agreement was observed in normal pulmonary arterial pressure (CO = 4.10 ± 1.14 and 4.08 ± 0.97 L/min, respectively), whereas IGR overestimated Fick in patients with PH-NW and those with PH-HW because of intrapulmonary shunting overestimation in hypoxemic patients. When patients with arterial oxygen saturation (SO 2 ) ≤90% were excluded, IGR and Fick agreement improved in PH-NW (CO = 4.90 ± 1.70 and 4.76 ± 1.35 L/min, respectively) and PH-HW (CO = 4.05 ± 1.04 and 4.10 ± 1.17 L/min, respectively). In hypoxemic patients, we estimated pulmonary shunt as Fick − pulmonary blood flow and calculated shunt as: −0.2423 × arterial SO 2 + 21.373 L/min. In conclusion, IGR is reliable for CO measurement in patients with PH with arterial SO 2 >90%. For patients with arterial SO 2 ≤90%, a new formula for shunt calculation is proposed.

Non-invasive inert gas rebreathing (IGR) has shown promising results in the determination of pulmonary blood flow. The volume of the rebreathing bag (V bag) is proposed by the system. However, elderly patients or those with severe pulmonary disease may be unable to rebreathe this volume entirely. We evaluated the effect of adapting V bag on the reproducibility of IGR. A total of 270 valid measurements were obtained from 45 patients with obstruction (group A), restriction (group B), and in healthy controls (group C). Two measurements for each of three different V bag of 1,200, 1,700, and 2,200 ml were conducted in the supine position. We found no statistically significant difference of the repeated measurements neither between the different V bag in groups A to C nor between the three groups for identical V bag. There was a weak yet significantly worse coefficient of variation between a V bag of 2,200 ml in group A compared with group C with 2,200 and 1,200 ml, respectively. Intraclass correlation coefficient and repeatability coefficient yielded significantly worse values in group A for a V bag of 2,200 ml compared with healthy controls and lower bag volumes. No difference could be found intraclass nor interclass in groups B and C. V bag can be altered between 1,200 and 2,200 ml in most situations without affecting the reproducibility. Attention has to be paid to extreme volumes in obstructive patients. Nevertheless, V bag should be chosen as large as possible and therefore has to be carefully adapted, particularly in patients with obstruction or restriction.

Objective To assess the feasibility and accuracy of inert gas rebreathing (IGR) pulmonary blood flow (Qp) estimation in mechanically ventilated pediatric patients, potentially providing real-time noninvasive estimates of cardiac output. Study design In mechanically ventilated patients in the pediatric catheterization laboratory, we compared IGR Qp with Qp estimates based upon the Fick equation using measured oxygen consumption (VO 2 ) (Fick True ); for context, we compared Fick True with a standard clinical short-cut, replacing measured with assumed VO 2 in the Fick equation (Fick LaFarge , Fick Lundell , Fick Seckeler ). IGR Qp and breath-by-breath VO 2 were measured using the Innocor device. Sampled pulmonary arterial and venous saturations and hemoglobin concentration were used for Fick calculations. Qp estimates were compared using Bland-Altman agreement and Spearman correlation. Results The final analysis included 18 patients aged 4-23 years with weight >15 kg. Compared with the reference Fick True , IGR Qp estimates correlated best and had the least systematic bias and narrowest 95% limits of agreement (results presented as mean bias ±95% limits of agreement): IGR −0.2 ± 1.1 L/min, r = 0.90; Fick LaFarge +0.7 ± 2.2 L/min, r = 0.80; Fick Lundell +1.6 ± 2.9 L/min, r = 0.83; Fick Seckeler +0.8 ± 2.5 L/min, r = 0.83. Conclusions IGR estimation of Qp is feasible in mechanically ventilated patients weighing >15 kg, and agreement with Fick True Qp estimates is better for IGR than for other Fick Qp estimates commonly used in pediatric catheterization. IGR is an attractive option for bedside monitoring of Qp in mechanically ventilated children.

The feasibility of replacing a conventional mass spectrometer (MS) with a specially modified multicomponent (O2, CO2, Freon 22, and SF6) acoustic infrared and paramagnetic (IR/PM) gas analyzer in inert gas-rebreathing and metabolic gas exchange measurements has been investigated. Rebreathing variables were determined simultaneously with the MS and IR/PM analyzers in duplicate measurements at rest and during submaximal exercise in 10 subjects. The differences (means +/- SD, IR/PM - MS) were 0.028 +/- 0.048 liters [functional residual capacity (FRC)], 0.18 +/- 0.38 l/min [cardiac output (Qc)], -0.006 +/- 0.030 l/min [O2 consumption (VO2)], and -33 +/- 108 ml [combined lung tissue and capillary blood volume (Vti,c)]. The coefficients of variation on repeated estimates were 5.8% (FRC), 5.4% (Qc), 6.2% (VO2), and 17% (Vti,c) with the IR/PM analyzer and 5.9% (FRC), 4.2% (Qc), 5.0% (VO2), and 9.8% (Vti,c) with the MS. The differences (IR/PM - MS) obtained in mixed-expirate measurements were -0.006 +/- 0.020 l/min (VO2) and 0.020 +/- 0.021 l/min (CO2 production). Breath-by-breath estimates of VO2 and CO2 production with the IR/PM analyzer were, on average, 2.4 and 4.4% higher than the MS estimates, respectively. Our results demonstrate that the IR/PM gas analyzer, when appropriately modified, can substitute for a complex MS in a variety of noninvasive pulmonary gas exchange measurements.

Stout et al. (J. Appl. Physiol. 38:913–918, 1975) suggested an open-circuit multibreath (MB) inert gas method for determining pulmonary capillary blood flow (Qc) in anesthetized dogs receiving artificial ventilation. In the present work we investigated the accuracy and reproducibility of the MB method in nine healthy human subjects at spontaneous ventilation, and we compared the MB method with the inert gas rebreathing (RB) method. Qc was calculated at rest and during exercise at 50 or 100 W, and experimental errors were evaluated in computer simulations of a two-alveoli lung model. The calculated mean Qc values of the MB method were 5.56 +/- 1.23 (SD), 10.02 +/- 0.78, and 13.2 +/- 0.84 l/min, and the mean difference (MB Qc - RB Qc) was not significantly different (P > 0.05). The variation in Qc of the MB method was found to be significantly larger than that in Qc of the RB method (P < 0.01). Random measurement errors and uneven distribution of ventilation contributed to the experimental errors. We conclude that the MB method is inferior to the RB method but that the MB method may be useful under exercise conditions.

When assessing the function of the cardiovascular system, cardiac output (CO) is a substantial parameter. For its determination, numerous non-invasive techniques have been proposed in the recent years including inert gas rebreathing (IGR) and impedance cardiography (ICG). The aim of our study was to evaluate whether a novel ICG algorithm (electrical velocimetry) and IGR can be used interchangeably in the clinical setting. A total of 120 consecutive stable patients were included resulting in two pairs of repeated non-invasive cardiac output measurements. The mean CO was 5.0 ± 1.2 l/min (range 2.6–8.6 l/min) using IGR and 4.4 ± 1.1 l/min (1.7–7.4 l/min) using ICG, respectively. Bland–Altman analysis revealed an acceptable agreement with a mean bias of 0.6 ± 1.2 l/min. We found a high reproducibility with a mean bias of 0.2 ± 0.7 l/min for IGR and 0.0 ± 0.3 l/min for ICG (p

In patients with cardiac failure, bioreactance-based cardiac output (CO) monitoring provides a valid non-invasive method for assessing cardiac performance during exercise. The purpose of this study was to evaluate the efficacy of this technique during strenuous exercise in healthy, trained individuals. Fourteen recreational cyclists, mean (SD) age of 34 (8) years and relative peak oxygen uptake of (VO(2)) 56 (6) ml kg(-1) min(-1), underwent incremental maximal exercise testing, whilst CO was recorded continuously using a novel bioreactance-based device (CO(bio)). The CO(bio) was evaluated against relationship with VO(2), theoretical calculation of arterial-venous oxygen difference (C(a - v) O(2)) and level of agreement with an inert gas rebreathing method (CO(rb)) using a Bland-Altman plot. Bioreactance-based CO measurement was practical and straightforward in application, although there was intermittent loss of electrocardiograph signal at high-intensity exercise. At rest and during exercise, CO(bio) was strongly correlated with VO(2) (r = 0.84; P < 0.001), however, there was evidence of systematic bias with CO(bio) providing lower values than CO(rb); mean bias (limits of agreement) -19% (14.6 to -53%). Likewise, calculated (C(a - v) O(2)) was greater when determined using CO(bio) than CO(rb) (P < 0.001), although both devices provided values in excess of those reported in invasive studies. Bioreactance-based determination of CO provides a pragmatic approach to the continuous assessment of cardiac performance during strenuous exercise in trained individuals. Our findings, however, suggest that further work is needed to refine the key measurement determinants of CO using this device to improve measurement accuracy in this setting.

European Journal of Applied Physiology, 108 (3), ISSN:1439-6319, ISSN:0301-5548, ISSN:1439-6327

BACKGROUND: Cardiac output (CO) is an important cardiac parameter, however its determination is difficult in clinical routine. Non-invasive inert gas rebreathing (IGR) measurements yielded promising results in recent studies. It directly measures pulmonary blood flow (PBF) which equals CO in absence of significant pulmonary shunt flow (Q(S)). A reliable shunt correction requiring the haemoglobin concentration (c(Hb)) as only value to be entered manually has been implemented. Therefore, the aim of the study was to evaluate the effect of various approaches to Q(S) correction on the accuracy of IGR. METHODS: Cardiac output determined by cardiac magnetic resonance imaging (CMR) served as reference values. The data was analysed in four groups: PBF without correcting for Q(S) (group A), shunt correction using the patients' individual c(Hb) values (group B), a fixed standard c(Hb) of 14.0 g dl(-1) (group C) and a gender-adapted standard c(Hb) for male (15.0 g dl(-1)) and female (13.5 g dl(-1)) probands each (group D). RESULTS: 147 patients were analysed. Mean CO(CMR) was 5.2 +/- 1.4 l min(-1), mean CO(IGR) was 4.8 +/- 1.3 l min(-1) in group A, 5.1 +/- 1.3 in group B, 5.1 +/- 1.3 l min(-1) in group C and 5.1 +/- 1.4 l min(-1) in group D. The accuracy in group A (mean bias 0.5 +/- 1.1 l min(-1)) was significantly lower as compared to groups B, C and D (0.1 +/- 1.1 l min(-1); P

Background: An easy, noninvasive and accurate technique for measuring cardiac output (CO) would be desirable for the diagnosis and therapy of cardiac diseases. Innocor, a novel inert-gas-rebreathing (IGR) system, has shown promising results in smaller studies. An extensive evaluation in a larger, less homogeneous patient collective is lacking. Methods: We prospectively assessed the accuracy and reproducibility of CO measurements obtained by IGR in 305 consecutive patients as compared to the noninvasive gold standard, cardiovascular magnetic resonance (CMR) imaging. Results: Bland-Altman analysis showed a good correspondence of the two methods for CO measurement with an average deviation of 0.2 ± 1.0 liters/min (mean ± SD) and a good reproducibility with a mean bias of 0.2 ± 0.5 liters/min. The accuracy of the present measurements at rest was significantly better in the physiological range than in higher or lower CO ranges. The error levels set forth by current recommendations were exceeded. Conclusion: The data show that IGR measurements are easy to perform and show good agreement with CMR; however, the technique appears to be less accurate in extreme CO ranges at rest. The clinical importance of the IGR method remains to be proven by further studies.

To the Editor: In heart failure (HF), measurement of cardiac output (CO) during exercise is important to define severity of the disease ([1][1]). Simultaneous measurements of oxygen consumption (Vo2) and CO during exercise allow calculation of arterio-venous oxygen difference [C(a-v)o2] ([2][2])

A new generation of non-invasive cardiac output monitors provides an alternative to using conventional invasive methods such as thermodilution and direct Fick. The Bioz.com measures changes in thoracic electrical bioimpedance (TEB) of the descending aorta. The Innocor uses the principle of inert gas rebreathing. Simultaneous TEB and thermodilution cardiac output measurements were taken from 27 patients undergoing right heart catheterisation. Linear regression analysis showed good correlation between thermodilution and TEB about the line y = 0.85x + 0.63 (r = 0.91, P