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Background: The use of inert gas rebreathing for the non-invasive cardiac output measurement has produced measurements comparable to those obtained by various other methods. However, there are no guidelines for the inert gas rebreathing method during a cardiopulmonary exercise test (CPET). In addition, there is also a lack of specific standards for assessing the non-invasive measurement of cardiac output during CPET, both for healthy patients and those suffering from diseases and conditions. Aim: This systematic review aims to describe the use of IGR for a non-invasive assessment of cardiac output during cardiopulmonary exercise testing and, based on the information extracted, to identify a proposed CPET report that includes an assessment of the cardiac output using the IGR method. Methods: This systematic review was conducted by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. PubMed, Web of Science, Scopus, and Cochrane Library databases were searched from inception until 29 December 2022. The primary search returned 261 articles, of which 47 studies met the inclusion criteria for this review. Results and Conclusions: This systematic review provides a comprehensive description of protocols, indications, technical details, and proposed reporting standards for a non-invasive cardiac output assessment using IGR during CPET. It highlights the need for standardized approaches to CPET and identifies gaps in the literature. The review critically analyzes the strengths and limitations of the studies included and offers recommendations for future research by proposing a combined report from CPET-IGR along with its clinical application. [ABSTRACT FROM AUTHOR]

Ketone monoester (KE) ingestion can induce hyperketonemia and blood acidosis. We previously found that acute ingestion of 0.6 g·kg−1 body mass KE increased exercise heart rate (HR) compared with placebo. Purpose: This study aimed to examine the effect of KE ingestion on exercise cardiac output (Q˙) and the influence of blood acidosis. We hypothesized that KE versus placebo ingestion would increase Q ˙, and coingestion of the pH buffer bicarbonate would mitigate this effect. Methods: In a randomized, double-blind, crossover manner, 15 endurance-trained adults (peak oxygen uptake (V̇O2peak), 60 ± 9 mL·kg−1·min−1) ingested either 0.2 g·kg−1 sodium bicarbonate or a salt placebo 60 min before exercise, and 0.6 g·kg−1 KE or a ketone-free placebo 30 min before exercise. Supplementation yielded three experimental conditions: basal ketone bodies and neutral pH (CON), hyperketonemia and blood acidosis (KE), and hyperketonemia and neutral pH (KE + BIC). Exercise involved 30 min of cycling at ventilatory threshold intensity, followed by determinations of V̇O2peak and peak Q ˙. Results: Blood [β-hydroxybutyrate], a ketone body, was higher in KE (3.5 ± 0.1 mM) and KE + BIC (4.4 ± 0.2) versus CON (0.1 ± 0.0, P < 0.0001). Blood pH was lower in KE versus CON (7.30 ± 0.01 vs 7.34 ± 0.01, P < 0.001) and KE + BIC (7.35 ± 0.01, P < 0.001). Q ˙ during submaximal exercise was not different between conditions (CON: 18.2 ± 3.6, KE: 17.7 ± 3.7, KE + BIC: 18.1 ± 3.5 L·min−1; P = 0.4). HR was higher in KE (153 ± 9 bpm) and KE + BIC (154 ± 9) versus CON (150 ± 9, P < 0.02). V̇O2peak (P = 0.2) and peak Q ˙ (P = 0.3) were not different between conditions, but peak workload was lower in KE (359 ± 61 W) and KE + BIC (363 ± 63) versus CON (375 ± 64, P < 0.02). Conclusions: KE ingestion did not increase Q ˙ during submaximal exercise despite a modest elevation of HR. This response occurred independent of blood acidosis and was associated with a lower workload at V̇O2peak. [ABSTRACT FROM AUTHOR]

Objective: Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope., Methods: This was a retrospective (2017-2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted., Results: Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting ( r = 0.53, p < 0.0001) and peak stroke volume ( r = 0.32, p = 0.009) by inert gas rebreathing and with peak oxygen pulse ( r = 0.61, p < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume ( Z -score -1.2 ± 1.3 vs. -0.36 ± 1.3, p = 0.01) and end-systolic volume ( Z -score -1.0 ± 1.4 vs. -0.1 ± 1.1, p = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, p = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, p = 0.03)., Discussion: Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.

Purpose: 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. Methods: 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. Results: Linear mixed-effects models revealed a significant bias of 25.7 ± 1.7 ml ( p < 0.0001 ) in stroke volume and 3.19 ± 0.18 l/min ( p < 0.0001 ) in cardiac output, with Nexfin measuring greater than Innocor in both variables. These values are in agreement with a Bland-Altman analysis. The correlation of stroke volume and cardiac output measurements between Nexfin and Innocor were r = 0.54 ( p < 0.0001 ) and r = 0.76 ( p < 0.0001 ) respectively. Conclusion: There is a poor agreement in absolute stroke volume and cardiac output values between measurement via PCA (Nexfin) and IGR (Innocor) in subjects who are exercising in simulated altered gravity environments. These results suggest that the chosen measurement method and device greatly impacts absolute measurements of cardiac output. However, there is a good level of agreement between the two devices when measuring relative changes. Either of these devices seem adequate to capture cardiac changes, but should not be solely relied upon for accurate measurement of absolute cardiac output. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Introduction: Sprint interval training (SIT), characterized by brief bouts of 'supramaximal' exercise interspersed with recovery periods, increases peak oxygen uptake ( V ˙ O 2 peak ) despite a low total exercise volume. Per the Fick principle, increased V ˙ O 2 peak is attributable to increased peak cardiac output ( Q ˙ 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 V ˙ O 2 peak , with most studies lasting ≤ 6 weeks. Purpose: To determine the effect of 12 weeks of SIT on Q ˙ peak , measured using inert gas rebreathing, and the relationship between changes in Q ˙ peak and V ˙ O 2 peak . Methods: 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. Results: Measurements performed before and after training showed that 12 weeks of SIT increased Q ˙ peak (17.0 ± 3.7 vs 18.1 ± 4.6 L/min, p = 0.01, partial η2 = 0.28) and V ˙ O 2 peak (2.63 ± 0.78 vs 3.18 ± 1.1 L/min, p < 0.01, partial η2 = 0.58). The changes in these two variables were correlated (r2 = 0.46, p < 0.01). Calculated peak a-vO2diff also increased after training (154 ± 22 vs 174 ± 23 ml O2/L; p < 0.01) and was correlated with the change in V ˙ O 2 peak (r2 = 0.33, p = 0.03). Exploratory analyses revealed an interaction (p < 0.01) such that Q ˙ peak increased in male (+ 10%, p < 0.01) but not female participants (+ 0.6%, p = 0.96), suggesting potential sex-specific differences. Conclusion: Twelve weeks of SIT increased Q ˙ peak by 6% in previously untrained participants and the change was correlated with the larger 21% increase in V ˙ O 2 peak . [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In postural stress, an increased preload volume leads to higher stroke volume (SV) according to the Frank-Starling law of the heart. The present study aimed to evaluate the hemodynamic response to postural stress using non-invasive inert gas rebreathing (IGR) in patients with normal as well as impaired left ventricular function. Hemodynamic measurements were performed in 91 patients undergoing cardiac magnetic resonance imaging (CMR). Mean cardiac output and SV determined by IGR were 4.4±1.3 l/min and 60±19 ml in the upright position, which increased significantly to 5.0±1.2 l/min and 75±23 ml in the supine position (P<0.01). Left ventricular systolic function was normal [ejection fraction (EF) ≥55%] in 42 patients as determined by CMR. In 21 patients, EF was mildly abnormal (45-54%), in 16 patients moderately abnormal (30-44%) and in 12 patients severely abnormal (<30%). An overall trend for a lower percentage change in SV (%ΔSV) was indicated with increasing impairment of ejection fraction. In patients with abnormal EF in comparison to those with normal EF, the %ΔSV was significantly lower (13% vs. 22%; P=0.03). Non-invasive measurement of cardiac function using IGR during postural changes may be feasible and detected significant difference in %ΔSV in patients with normal and impaired EF according to the Frank-Starling law of the heart. Several clinical scenarios including cases of heart rhythm disturbances or pulmonary or congenital heart disease are worthy of further investigation. [ABSTRACT FROM AUTHOR]

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 < 0.01 with coefficient of variation of 6.0 %), at rest (r = 0.90, p < 0.01 with coefficient of variation of 5.1 %), and during exercise (r = 0.89, p < 0.01 with coefficient of variation 3.3 %). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the clinical value of cardiac output (CO) measurements using the inert gas rebreathing (IGR) method during the 6-minute walk test (6MWT) in evaluation of chronic heart failure (CHF). Methods and results A total of 56 CHF patients in our hospital who conformed to the Framingham CHF diagnostic criteria were recruited to this study from October 2007 to February 2009. Subjects were asked to complete a 6MWT and a bicycle exercise test. The CO was measured during both tests using IGR. B-type natriuretic peptide (BNP) levels and the left ventricular ejection fraction (LVEF) were measured at rest. The 6MWT did not correlate with BNP, LVEF, peak cardiac output (PCO), or CO during the 6MWT (CO6MWT). A negative correlation between CO6MWT and BNP as well as a strong correlation between CO6MWT and PCO was observed. When atrial fibrillation and valvular heart disease patients were excluded, CO6MWT and LVEF became significantly correlated. After grouping patients into tertiles according to their PCO values, the PCO remained correlated with CO6MWT within each group. The mean difference between CO6MWT and PCO decreased with decreases in the mean PCO in each group. No significant differences were found in the third tertile (PCO < 10.1 L/min). Conclusions The IGR method during 6MWT is safe and reliable to evaluate cardiac function in patients with CHF. [ABSTRACT FROM AUTHOR]

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 (QFick-M), Innocor (inert gas rebreathing; QInn), Physioflow (impedance cardiography; QPhys), and Nexfin (pulse contour analysis; QPulse) 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 QFick-M, QInn, QPhys and QPulse, 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. [ABSTRACT FROM AUTHOR]

Aims High altitude exposure for the purpose of tourism is very popular in mountainous regions and is considered to be safe for patients with stable CAD and preserved LV function. The purpose of this study was to evaluate the haemodynamic response to exercise and electrical stability by Holter monitoring in patients with chronic heart failure ( HF) and an EF <40%. Methods and results We studied 29 HF patients with a peak VO2 >50% of the predicted (25 men, age 60.0 ± 8.9 years, EF 28.8 ± 5.4%) at 540 and 3454 m after an ascent using public transport. Assessments of exercise capacity (cardiopulmonary exercise test), haemodynamic response (inert gas rebreathing system), and susceptibility to arrhythmias (Holter ECG recording) were performed. None of the patients (19 with ischaemic heart disease, 11 with an implantable cardioverter defibrillator) had to return prematurely to the lowland site. Two patients presented symptoms of mild mountain sickness, and one patient developed a self-limited ventricular tachycardia during maximal exercise at high altitude. Mean peak VO2 at the lowland site was 18.5 ± 3.6 mL/min/kg and decreased by 22.2% ( P < 0.001) at high altitude. Mean resting heart rate increased from 74.3 ± 12.3 to 83.3 ± 13.4 b.p.m., P < 0.001. No statistically significant difference in premature ventricular contractions (92 ± 150/h at 540 m vs. 111 ± 196/h at 3454 m, P = 0.284) was noted. Conclusion Patients with stable chronic HF and a peak VO2 >50% of the predicted tolerate a short exposure to an altitude of 3454 m well, even during exercise. However, it cannot be excluded that the susceptibility to ventricular tachyarrhythmias during exercise is increased in some subjects. [ABSTRACT FROM AUTHOR]

Purpose: Commercial parabolic flights accessible to customers with a wide range of health states will become more prevalent in the near future because of a growing private space flight sector. However, parabolic flights present the passengers' cardiovascular system with a combination of stressors, including a moderately hypobaric hypoxic ambient environment (HH) and repeated gravity transitions (GT). Thus, the aim of this study was to identify unique and combined effects of HH and GT on the human cardiovascular, pulmonary and fluid regulation systems. Methods: Cardiac index was determined by inert gas rebreathing (CI), and continuous non-invasive finger blood pressure (FBP) was repeatedly measured in 18 healthy subjects in the standing position while they were in parabolic flight at 0 and 1.8 G. Plasma volume (PV) and fluid regulating blood hormones were determined five times over the flight day. Eleven out of the 18 subjects were subjected to an identical test protocol in a hypobaric chamber in ambient conditions comparable to parabolic flight. Results: CI in 0 G decreased significantly during flight (early, 5.139 ± 1.326 L/min; late, 4.150 ± 1.082 L/min) because of a significant decrease in heart rate (HR) (early, 92 ± 15 min; late, 78 ± 12 min), even though the stroke volume (SV) remained the same. HH produced a small decrease in the PV, both in the hypobaric chamber and in parabolic flight, indicating a dominating HH effect without a significant effect of GT on PV (−52 ± 34 and −115 ± 32 ml, respectively). Pulmonary tissue volume decreased in the HH conditions because of hypoxic pulmonary vasoconstriction (0.694 ± 0.185 and 0.560 ± 0.207 ml) but increased at 0 and 1.8 G in parabolic flight (0.593 ± 0.181 and 0.885 ± 0.458 ml, respectively), indicating that cardiac output and arterial blood pressure rather than HH are the main factors affecting pulmonary vascular regulation in parabolic flight. Conclusion: HH and GT each lead to specific responses of the cardiovascular system in parabolic flight. Whereas HH seems to be mainly responsible for the PV decrease in flight, GT overrides the hypoxic pulmonary vasoconstriction induced by HH. This finding indicates the need for careful and individual medical examination and, if necessary, health status improvement for each individual considering a parabolic flight, given the effects of the combination of HH and GT in flight. [ABSTRACT FROM AUTHOR]

Purpose: Non-invasive inert gas rebreathing (IGR) has shown promising results in the determination of pulmonary blood flow. The volume of the rebreathing bag ( V) 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 on the reproducibility of IGR. Methods: 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 of 1,200, 1,700, and 2,200 ml were conducted in the supine position. Results: We found no statistically significant difference of the repeated measurements neither between the different V in groups A to C nor between the three groups for identical V. There was a weak yet significantly worse coefficient of variation between a V 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 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. Conclusions: V 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 should be chosen as large as possible and therefore has to be carefully adapted, particularly in patients with obstruction or restriction. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: A total of 120 consecutive stable patients were included resulting in two pairs of repeated non-invasive cardiac output measurements. Results: 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 < 0.001), respectively. There was a statistically significant difference for unphysiological circulatory conditions represented by values of 2.6-4.1 l/min and 5.6-8.6 l/min. Conclusions: Both non-invasive techniques are associated with low operating costs and require only a few expendable items for the rapid determination of cardiac function. We found an acceptable agreement between IGR and ICG as well as a high reproducibility, which was statistically significant higher for ICG. For cardiac output states exceeding the physiological range, we found a statistically significant difference. Consequently, values of cardiac function determined by either method should not be used interchangeably in the clinical setting. [ABSTRACT FROM AUTHOR]

Cardiac output (CO) is an important parameter for diagnosis and therapy of heart diseases, but it is still difficult to determine. Innocor, a novel noninvasive inert gas rebreathing (IGR) system, has shown promising results. However, the impact of pulmonary diseases on IGR remains unclear. The aim of the study therefore was to assess the accuracy and reliability of IGR in patients with distinct chronic lung disease. A total of 96 patients were enrolled, including 48 consecutive patients with variant lung diseases (group A) and 48 pair-matched pulmonary healthy patients (group B). CO was measured with cardiac magnetic resonance imaging (CMR) and IGR. Lung function testing was done by spirometry [FEV/FVC (forced expiratory volume in one second/forced vital capacity), VC (vital capacity)] and determination of the diffusing capacity of the lung for carbon monoxide divided by alveolar volume (DLCO/VA). In group A we found a mean CO of 4.7 ± 1.3 L/min by IGR and 4.9 ± 1.2 L/min by CMR. Group B showed a mean CO of 4.8 ± 1.4 L/min by IGR and 5.0 ± 1.3 L/min by CMR. Bland–Altman analysis revealed good correspondence between CMR and IGR, with an average deviation of 0.1 ± 1.0 L/min in group A and 0.1 ± 1.0 L/min in group B ( p = 0.99). Multiple regression analysis for the pulmonary parameters did not show a statistically significant impact on the mean bias of CO measurements (FEV/FVC: r = 0.01, p = 0.91; VC: r = −0.2, p = 0.13; and DLCO/VA: r = 0.04, p = 0.82). IGR allows a feasible determination of CO even in patients with lung diseases. The accuracy of the IGR method is not influenced by either pulmonary obstructive and restrictive diseases or a reduced DLCO. [ABSTRACT FROM AUTHOR]

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) [ABSTRACT FROM AUTHOR]

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. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cardiac output (Q) and stroke volume (V(S)) represent primary determinants of cardiovascular performance and should therefore be determined for performance diagnostics purposes. Since it is unknown, whether measurements of Q and V(S) can be performed by means of Innocor during standard graded exercise tests (GXTs), and whether current GXT stages are sufficiently long for the measurements to take place, we determined Q and V(S) at an early and late point in time on submaximal 2 min GXT stages. 16 male cyclists (age 25.4 +/- 2.9 years, body mass 71.2 +/- 5.0 kg) performed three GXTs and we determined Q and V(S) after 46 and 103 s at 69, 77, and 85% peak power. We found that the rebreathings could easily be incorporated into the GXTs and that Q and V(S) remained unchanged between the two points in time on the same GXT stage (69% peak power, Q: 18.1 +/- 2.1 vs. 18.2 +/- 2.3 l min(-1), V(S): 126 +/- 18 vs. 123 +/- 21 ml; 77% peak power, Q: 20.7 +/- 2.6 vs. 21.0 +/- 2.3 l min(-1), V(S): 132 +/- 18 vs. 131 +/- 18 ml; 85% peak power, Q: 21.6 +/- 2.4 vs. 21.8 +/- 2.7 l min(-1), V(S): 131 +/- 17 vs. 131 +/- 22 ml). We conclude that Innocor may be a useful device for assessing Q and V(S) during GXTs, and that the adaptation of Q and V(S) to exercise-to-exercise transitions at moderate to high submaximal power outputs is fast enough for 1 and 2 min GXT stage durations. [ABSTRACT FROM AUTHOR]

Cardiac output represents the primary determinant of cardiovascular function. Therefore, understanding how cardiac output is regulated during exercise is crucial. A recently developed tool for determining cardiac output is the Innocor™ rebreathing system, which also incorporates an ergospirometry unit. So far, lnnocorlM's test-retest reliability under exercise conditions has not been determined in healthy participants. Therefore, 15 male and 15 female healthy participants [30.6 y (SD 4.5): 68.0 kg (SD 10.5)] performed 2 test sessions, each consisting of 2 graded exercise tests to volitional exhaustion. We determined intra- and inter-session reliability of cardiac output, oxygen consumption, carbon dioxide output, and ventilation at 130W and at peak exercise. For cardiac output, we found averaged coefficients of variation ranging from 4.3 (intra-session, 130W) to 10.0% (inter-session, rest). For oxygen consumption, coefficients of variation ranged from 3.4 (intra-session, peak) to 5.7%(inter-session, peak). Coefficients of variation for carbon dioxide output were between 4.4 (intra-session, peak) and 6.6% (inter-session. peak), and for ventilation between 5.1 (intra-session, 130 W) and 7.0%(intra-session, peak). lnnocor™ delivers safe and reliable measurements of cardiac output, gas exchange, and ventilation. Therefore, lnnocor™ can be used to assess these parameters in exercise physiology studies as well as in performance diagnostics. [ABSTRACT FROM AUTHOR]

Aims: Data on moderately cold water immersion and occurrence of arrhythmias in chronic heart failure (CHF) patients are scarce. [ABSTRACT FROM PUBLISHER]

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 ( QS). A reliable shunt correction requiring the haemoglobin concentration ( cHb) 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 QS 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 QS (group A), shunt correction using the patients’ individual cHb values (group B), a fixed standard cHb of 14·0 g dl−1 (group C) and a gender-adapted standard cHb for male (15·0 g dl−1) and female (13·5 g dl−1) probands each (group D). Results: 147 patients were analysed. Mean COCMR was 5·2 ± 1·4 l min−1, mean COIGR 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<0·01). Conclusion: IGR allows a reliable non-invasive determination of CO. Since PBF significantly increased the measurement bias, shunt correction should always be applied. A fixed cHb of 14·0 g dl−1 can be used for both genders if the exact cHb value is not known. Nevertheless, the individual value should be used if any possible. [ABSTRACT FROM AUTHOR]

Physical maneuvers can be applied to abort or delay an impending vasovagal faint. These countermaneuvers would be more beneficial if applied as a preventive measure. We hypothesized that, in patients with recurrent vasovagal syncope, leg crossing produces a rise in cardiac output (CO) and thereby in blood pressure (BP) with an additional rise in BP by muscle tensing. We analyzed the age and gender effect on the BP response. To confirm that, during the maneuvers. Modelfiow CO changes in proportion to actual CO. 10 healthy subjects performed the study protocol with CO evaluated simultaneously by Modelflow and by inert gas rebreathing. Changes in Modelflow CO were similar in direction and magnitude to inert gas rebreathing-determined CO changes. Eighty-eight patients diagnosed with vasovagal syncope applied leg crossing after a 5-mm free- standing period. Fifty-four of these patients also applied tensing of leg and abdominal muscles. Leg crossing produced a significant rise in CO (+9.5%; P < 0.01) and thereby in mean arterial pressure (+3.3%; P < 0.01). Muscle tensing produced an additional increase in CO (+8.3%; P < 0.01) and mean arterial pressure (+7.8%; P < 0.01). The rise in BP during leg crossing was larger in the elderly. [ABSTRACT FROM AUTHOR]

Abstract: 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 <0.001). Bland–Altman analysis showed a good agreement of measurements with a bias of 0.4±1.0 l/min (mean±standard deviation). Both methods showed a good reproducibility. CWD measurements were not possible in 14% of patients while IGR measurements were not possible in 5% of patients (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. [Copyright &y& Elsevier]

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/VCO 2 ) 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  < 0.01) and carbon dioxide output were significantly higher at cardiopulmonary exercise testing than at cardiopulmonary exercise test+cardiac output, whereas VE/VCO 2 slope was higher at cardiopulmonary exercise test+cardiac output (30 (27-35) vs 33 (28-37), p  < 0.01)., Conclusion: The similar anaerobic threshold and peak oxygen uptake in the two tests with a lower peak workload and higher VE/VCO 2 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/VCO 2 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 < 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.

Introduction: Intrathoracic shunt quantification is a major factor for appropriate clinical management of heart and pulmonary diseases. Intracardiac shunts quantified by pulmonary to systemic output ratio (Qp/Qs) are generally assessed by Doppler echocardiography, MRI or catheterisation. Recently, some authors have suggested the concomitant use of thoracic bioimpedance (TB) and inert gas rebreathing (IGR) techniques for shunt quantification. The purpose of this study is to validate the use of this approach under conditions where shunt fraction is directly quantified such as in patients with isolated atrial septal defect (ASD)., Methods and Analysis: This trial is a prospective, observational single-centre, non-blinded study of adults seen for percutaneous closure of ASD. Qp/Qs ratio will be directly measured by Doppler echocardiography and direct Fick. IGR and TB will be used simultaneously to measure the cardiac output before and after closure: the ratio of outputs measured by IGR and TB reflecting the shunt fraction. The primary outcome will be the comparison of shunt values measured by TB-IGR and Doppler echocardiography., Ethics and Dissemination: The study has been approved by an independent Research Ethics Committee (2017-A03149-44 Fr) and registered as an official clinical trial. The results will be published in a peer-reviewed journal., Trial Registration Number: NCT03437148; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study was to assess the clinical value of cardiac output (CO) measurements using the inert gas rebreathing (IGR) method during the 6-minute walk test (6MWT) in evaluation of chronic heart failure (CHF)., Methods and Results: A total of 56 CHF patients in our hospital who conformed to the Framingham CHF diagnostic criteria were recruited to this study from October 2007 to February 2009. Subjects were asked to complete a 6MWT and a bicycle exercise test. The CO was measured during both tests using IGR. B-type natriuretic peptide (BNP) levels and the left ventricular ejection fraction (LVEF) were measured at rest. The 6MWT did not correlate with BNP, LVEF, peak cardiac output (PCO), or CO during the 6MWT (CO6MWT). A negative correlation between CO6MWT and BNP as well as a strong correlation between CO6MWT and PCO was observed. When atrial fibrillation and valvular heart disease patients were excluded, CO6MWT and LVEF became significantly correlated. After grouping patients into tertiles according to their PCO values, the PCO remained correlated with CO6MWT within each group. The mean difference between CO6MWT and PCO decreased with decreases in the mean PCO in each group. No significant differences were found in the third tertile (PCO < 10.1 L/min)., Conclusions: The IGR method during 6MWT is safe and reliable to evaluate cardiac function in patients with CHF.

Aims: In chronic heart failure (CHF), changes in cardiac function define the course of the disease. The cardiac index (CI) is the most adequate indicator of cardiac function. Interpretation of serial CI measurements, however, requires knowledge of the biological variation of CI. Because measurements of CI can be confounded by the clinical situation or the method applied, biological variation might be subject to the same confounders., Methods and Results: We prospectively included 50 CHF patients who met rigid criteria for clinical stability. CI was measured by both inert gas rebreathing (IGR) and impedance cardiography (ICG) in weekly intervals over 3 weeks-each measurement performed at rest (IGR rest /ICG rest ) and during low-exercise 10 Watt pedalling (IGR 10W /ICG 10W ). Intra-class correlation coefficients (ICCs), reference change values, and minimal important differences of CI were determined for IGR rest , ICG rest , IGR 10W , and ICG 10W . Impedance cardiography and IGR showed moderate agreement at rest (20% (6-36)) and good agreement at 10 Watt (-4% (-23-16)). Depending on time interval, measurement modality for CI, and mode, ICC ranged between 0.42 and 0.78, ICC values for IGR were lower than those for ICG. Reference change value ranged between 3 and 15%, and minimal important difference ranged between 0.2 and 0.5 L/min/m 2 . Values for IGR were lower at rest and higher at 10 Watt than those for ICG., Conclusion: Non-invasive measurements of CI are stable over time. Measurement modalities for CI, however, are not interchangeable. Biological variation is less pronounced when obtained by ICG. The influence of low-level exercise on stability of CI depends on the measurement modality.