A Validation Study Comparing Cheetah Monitor Cardiac Output to Thermodilution Cardiac Output in Patients with Severe Mitral Regurgitation

A Validation Study Comparing Cheetah Monitor Cardiac Output to Thermodilution Cardiac Output in Patients with Severe Mitral Regurgitation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Validation Study Comparing Cheetah Monitor Cardiac Output to Thermodilution Cardiac Output in Patients with Severe Mitral Regurgitation Ludmil Mitrev, Michael Rosenbloom, Georges Kaddissi, Ahmed Awad, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6214798/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Monitoring cardiac output (CO) is helpful in the perioperative management of the patient with severe mitral regurgitation (MR). We assessed the accuracy and precision of the Cheetah CO monitor in patients with moderate or severe MR undergoing right and left heart catheterization as part of their pre-operative evaluation for mitral valve surgery. Cheetah CO was obtained concurrently with thermodilution CO (TD CO). Bias data was non-normally distributed; therefore, a non-parametric equivalent to Bland and Altman limits of agreement was used. Additionally, the proportions of differences between the experimental and reference method that were ≤ 0.5 L/min, ≤ 1 L/min, and > 1L/min were calculated. Twenty-seven subjects were enrolled and completed the study. The median difference between Cheetah and TD CO measurements was − 0.82 L/min, and the 5th and 95th centiles were − 6.05 L/min and 3.25 L/min, respectively. Of all differences, 25.9%, 51.9%, and 48.1% were ≤ 0.5 L/min, ≤ 1 L/min, and > 1 L/min. No proportional bias was present. We conclude that the Cheetah CO measurements in patients with moderate to severe MR cannot be used interchangeably with TD CO due to a large bias and imprecision. Health sciences/Cardiology Health sciences/Medical research mitral regurgitation cardiac output non-invasive cardiac output monitoring Cheetah monitor Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION The Cheetah monitor (Baxter Healthcare Corporation Inc., Deerfield, IL, USA) is a non-invasive monitor that estimates cardiac output (CO) based on transthoracic bioreactance. It is of practical importance to know the extent to which the CO estimation provided by the device can be used interchangeably with thermodilution CO (TD CO) in patients with significant mitral regurgitation (MR). Cold right heart bolus TD CO is well-established as an accurate and precise method of CO measurement in patients with MR, but a pulmonary artery catheter is not always used in contemporary practice and non-invasive methods that perform with an acceptable degree of accuracy and precision could be useful in the care of patients with MR. [ 1 , 2 ] Left and right heart catheterization is standard of care in the pre-operative evaluation of patients with severe MR. While left heart catheterization (LHC) assesses peak and mean pressure gradients across the aortic valve, the state of the patient’s coronary vasculature, and provides an angiographic assessment of left ventricular performance, right heart catheterization (RHC) can be performed to measure the various pressures from superior vena cava to the pulmonary artery, to obtain mixed venous blood sampling, and estimate CO using the modified Fick method. Since TD CO can be obtained in patients who are undergoing right heart catheterization, the primary aim of this study was to assess the bias and limits of agreement between Cheetah CO and TD CO. A secondary aim was to assess the bias and limits of agreement between Fick CO and TD CO in these patients. TD CO was the method of reference in both cases. The trending ability of the Cheetah monitor was not assessed due to the short procedure time and the lack of significant hemodynamic changes during cardiac catheterization. RESULTS In total, 26 participants enrolled and completed the study. Similar numbers of women and men participated, and most participants (62%) had severe mitral regurgitation (Table 1). Table 1. Baseline demographic and clinical characteristics Study participants (N = 26) Age in years, mean (SD) 64.6 (9.1) Gender, n (%) Female 12 (46) Male 14 (54) Body mass index in kg/m 2 , mean (SD) 25.9 (4.4) Body surface area in m 2 , mean (SD) 1.9 (0.2) Mitral regurgitation severity, n (%) Moderate 7 (27) Moderate/Severe 3 (12) Severe 16 (62) SD, standard deviation Most subjects had no or mild tricuspid regurgitation; only two had moderate tricuspid regurgitation. Two subjects (11%) had severely depressed ejection fraction (EF) and 6 (22%) had moderately depressed EF, with the remained having normal EF. All study subjects were breathing spontaneously and were in steady state during all measurements. They received on average 1.4 milligrams midazolam and 66.4 micrograms fentanyl for conscious sedation during the catheterization procedure. Primary Aim Distribution of differences between Cheetah and TD CO measurements Differences between Cheetah and TD CO measurements in a normal-quantile plot followed a non-linear path (Figure 1). A Shapiro-Wilk test indicated a non-normal distribution ( P = .038). Correlation between Cheetah and TD CO measurements Spearman correlation analysis indicated a weak to moderate correlation (ρ = .393, P = .048) between Cheetah and TD CO measurements (Figure 2). Agreement between Cheetah and TD CO measurements A difference plot between Cheetah and TD CO measurements indicated poor agreement between Cheetah and TD CO measurements (Figure 3). The median difference between Cheetah and TD CO measurements was 0.86 L/min. The 5 th and 95 th centile were -3.34 L/min and 6.01 L/min, respectively. Of all differences, 23.1%, 53.8%, and 46.2% were 0.5 ≤ L/min, ≤ 1 L/min, and >1 L/min, respectively. There was no evidence of proportional bias (ρ = -.138, P = .496). The repeated precision of the TD reference was 4%, whereas the precision of Cheetah CO measurements was 2%, indicating that differences between measurement techniques were likely not attributable to repeatability variation. Secondary Aim Distribution of differences between Fick and TD CO measurements Differences between Fick and TD CO measurements in a normal-quantile plot followed a non-linear path (Figure 4). A Shapiro-Wilk test indicated a non-normal distribution ( P = .017) Correlation between Fick and TD CO measurements Spearman correlation analysis indicated a moderate correlation (ρ = .670, P < .001) between Fick and TD CO measurements (Figure 5). Agreement between Fick and TD CO measurements A difference plot between Fick and TD CO measurements indicated moderate agreement between Fick and TD CO measurements (Figure 6). The median difference between Fick and TD CO measurements was -0.18 L/min. The 5 th and 95 th centile were -1.52 L/min and 3.36 L/min, respectively. Of all differences, 45.4%, 63.6%, and 36.4% were 0.5 ≤ L/min, ≤ 1 L/min, and >1 L/min, respectively. There was no evidence of proportional bias (ρ = .003, P = . 984). DISCUSSION Our study found poor agreement between Cheetah and TD CO in patients with moderate to severe MR, and moderate agreement between the modified Fick CO and TD CO. The median difference between Cheetah and TD CO measurements was 0.86 L/min, whereas the median difference between Fick and TD CO measurements was -0.18 L/min. The differences between the measurements were not normally distributed, which could have been the result of a small sample. We therefore did not use classic Bland and Altman limits of agreement of ±1.96 standard deviations, but a non-parametric equivalent, namely the 5 th and 95 th centiles of the differences between the method of interest and the reference method (Cheetah and Fick CO vs. TD CO, respectively). These limits were wide in the case of Cheetah CO (-3.34 L/min and 6.01 L/min), and less so in the case of Fick CO (-1.52 L/min and 3.36 L/min). In either case, there was no evidence of proportional bias. Considerable variability exists concerning the biases and limits of agreement of CO monitors relative to a reference method such as TD CO. [3-8] Prior studies of Cheetah CO have shown smaller biases and LOA compared to our findings. One study comparing Cheetah CO to a continuous TD CO system in intensive care patients showed that Cheetah CO had a bias of +0.16 L/min and limits of agreement of ±1.04 L/min. [9] Another study in intensive care patients showed a bias of -0.09 L/min and limits of agreement of ±2.4 L/min. [10] Yet another study evaluated Cheetah CO to Fick CO and TD CO in subjects with pulmonary hypertension. [11] Bias and limits of agreement of Cheetah CO compared to Fick CO were 0.21±2.3 L/min. Bias and limits of agreement of Cheetah CO compared to TD CO were -0.37±2.6 L/min. In the same study, the bias and limits of agreement of Fick CO against TD CO were -0.91±2.1 L/min. A meta-analysis of studies examining the bias and precision of non-invasive CO monitors found a random-effects pooled bias and limits of agreement of −0.13 and 2.23 litres min −1 , respectively. [12] The percentage error was 47%, and there was significant inter-study heterogeneity. However, only one of the studies in this meta-analysis compared the Cheetah CO to a method of reference (partial carbon dioxide rebreathing method). [13] Weaknesses of our study include the relatively small sample size and the non-normally distributed data, necessitating the use of non-parametric methods. In their 1999 paper, Bland and Altman pointed out that such methods are “generally less reliable than those obtained using normal distribution theory.” [14] In addition, 11% of patients in our study had severely depressed ejection fraction, raising the possibility of low flow states affecting the measurements. Two subjects had moderate tricuspid regurgitation (TR). This also raises the question of whether their TR could have affected the TD CO measurements. The bias and the 5 th and 95 th centiles of the differences between Cheetah and TD CO were considerably higher and wider in our study population compared to the results of the other studies of Cheetah CO referenced herewith. We conclude that Cheetah CO cannot be used interchangeably with TD CO in patients with severe MR. An overestimation of CO by almost 1 L/min by the Cheetah monitor would be clinically significant even in subjects with high CO. This is not to say that the Cheetah monitor is not valuable in patients with no MR. Additionally, this study did not evaluate the monitor’s trending ability as the RHC and LHC are short procedures and are not usually associated with major hemodynamic changes. METHODS The Cooper University HealthCare Institutional Review Board (IRB) approved the study (IRB #19-210EX). All procedures were in accordance with the ethical standards of the local IRB and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants in the study provided written informed consent. Cheetah Non-Invasive Cardiac Output Monitor The Cheetah monitor uses bioreactance to estimate cardiac output. [9,10,15] The pulsatile flow of blood in the large thoracic arteries produces phase shifts in an alternating current passed through the chest via two pairs of external electrodes, on on either side of the chest above and below the diaphragm. [6] The phase shifts are measured, and stroke volume (SV) is estimated based on its correlation with the phase shifts and the thoracic voltage. The Cheetah signal effectively measures the blood volume change in the thorax between systole and diastole. The monitor has been validated in spontaneously breathing and mechanically ventilated patients, as well as in patients with arrhythmias. Unlike bioimpedance, the bioreactance method is independent from the distance between the electrodes. [5] Because the electrodes are paired, two separate signals are obtained and averaged to produce the SV estimate. Inclusion and Exclusion Criteria Subjects were enrolled if they met the following criteria: 1. Had planned RHC and LHC 2. Were at least 18 years of age 3. Provided written informed consent to participate in the study. 4. Had at least moderate to severe MR (echocardiographic grade 3 or 4 MR) on pre-referral transthoracic echo 5. The subjects’ height and weight was accurately documented. Subjects were excluded if the following conditions were present: Other valve pathology graded greater than moderate (aortic, tricuspid, pulmonic) Did not have a pre-procedure transthoracic echocardiogram (TTE) Chronic atrial fibrillation with irregular pulse Intracardiac shunt Intra-aortic balloon pump or other circulatory assist device Intubated or unconscious patients Known pregnancy Emergency heart catheterization Uncompensated congestive heart failure Current participation in an investigational drug or device study that could interfere with the study endpoints Anticipated reason why TD CO could be obtained. Cardiac Output Measurements RHC and LHC was performed using routine methods. Catheterization data were recorded using the McKesson Cardiology Station Release 13.0 (McKesson Corporation, San Francisco, CA). All system clocks were matched and time-stamped data was exported from the Cheetah monitor on a USB drive. A Swan-Ganz catheter was used during RHC to measure TD CO with intermittent cold saline bolus. The TD CO was averaged from 3, 4 or 5 boluses as determined by the interventional cardiologist on visual inspection of the thermodilution curve. The Cheetah CO values were exported from the Cheetah monitor and averaged over the same period during which the TD CO measurements were made. The modified Fick CO was obtained from aortic and mixed venous blood samples using the Fick equation: where CO = cardiac output, VO 2 = estimated O 2 consumption, CaO 2 = arterial oxygen content, CvO 2 = venous oxygen content. VO 2 was estimated as 125 millilitres O 2 x Body Surface Area (BSA). The physiologic equation for CaO 2 and CvO 2 was used: Oxygen content = 1.36 x Hgb [mg/dl] x SaO 2 or SvO 2 where SaO 2 = arterial oxygen saturation, SvO 2 = mixed venous oxygen saturation, and Hgb = haemoglobin. Because the estimated rather than the measured VO 2 value was used, we refer to Fick CO as the “modified Fick CO”. Statistical analysis Baseline demographic and clinical characteristics were analysed using descriptive statistics. A two-sided P -value < .05 was considered statistically significant for all analyses. Primary aim A previously published stepwise approach and checklist for CO monitor validation studies were used to compare the Cheetah CO measurements with the reference TD CO measurements. [16] Differences between the Cheetah and TD CO measurements were checked for normality using a normal-quantile plot and the Shapiro-Wilk test. [16] Considering these assessments indicated that the differences did not follow a normal distribution, non-parametric approaches were used for correlation analysis as well as the difference plot. [14,16] As a non-parametric equivalent to limits of agreement, the 5 th and 95 th centiles of the differences between Cheetah and TD CO measurements were calculated. [14] Additionally, the proportions of differences between Cheetah and TD CO measurements ≤ 0.5 L/min, ≤ 1 L/min, and >1L/min were calculated. [14] The proportionality of differences between Cheetah and TD CO measurements was assessed by plotting a regression line in the difference plot and Spearman rank order correlation. [16] Cheetah and TD CO repeated measurement precision were calculated using the coefficient of error (CE). [16,17] Secondary aim Differences between Fick CO and TD CO measurements were checked for normality using a normal-quantile plot and the Shapiro-Wilk test. [16] Considering these assessments indicated that the differences did not follow a normal distribution, non-parametric approaches were used for correlation analysis as well as the difference plot. [14,16] As a non-parametric equivalent to limits of agreement, the 5 th and 95 th centiles of the differences between Fick and TD CO measurements were calculated. [14] Additionally, the proportions of differences between Fick and TD CO measurements ≤ 0.5 L/min, ≤ 1 L/min, and >1L/min were calculated. [14] The proportionality of differences between Fick and TD CO measurements was assessed by plotting a regression line in the difference plot and Spearman rank order correlation. [16] Declarations Competing Interests: The authors declare no competing interests. Funding: This was an investigator-initiated study supported by an unrestricted research grant by Baxter Healthcare Corporation Inc., Deerfield, IL, USA, awarded to Cooper University Healthcare. In addition, Baxter supplied the Cheetah monitor sensors necessary for the measurements. The funder was not involved in the conduct of the research, data interpretation, manuscript drafting, or the decision to publish. Author Contribution L.M. and N.v.H. participated in study conception, design, data analysis and manuscript preparation. N.v.H. prepared all figures and tables. L.M., M.R., G.K., A.A., J.A., J.O. and K.T. participated in enrolment, data collection and manuscript editing. Acknowledgement We acknowledge Brian McEniry, CRC, for his outstanding contributions to the data collection and management of this study. Data Availability The complete dataset is available on request from the corresponding author by emailing [email protected] . References Stetz, C. W., Miller, R. G., Kelly, G. E. & Raffin, T. A. Reliability of the thermodilution method in the determination of cardiac output in clinical practice. The American review of respiratory disease 126 , 1001-1004, doi:10.1164/arrd.1982.126.6.1001 (1982). Nishikawa, T. & Dohi, S. Errors in the measurement of cardiac output by thermodilution. Canadian journal of anaesthesia = Journal canadien d'anesthesie 40 , 142-153, doi:10.1007/BF03011312 (1993). Dhingra, V. K., Fenwick, J. C., Walley, K. R., Chittock, D. R. & Ronco, J. J. Lack of agreement between thermodilution and fick cardiac output in critically ill patients. Chest 122 , 990-997, doi:10.1378/chest.122.3.990 (2002). Espersen, K. et al. Comparison of cardiac output measurement techniques: thermodilution, Doppler, CO2-rebreathing and the direct Fick method. Acta anaesthesiologica Scandinavica 39 , 245-251 (1995). Keren, H., Burkhoff, D. & Squara, P. Evaluation of a noninvasive continuous cardiac output monitoring system based on thoracic bioreactance. American journal of physiology. Heart and circulatory physiology 293 , H583-589, doi:10.1152/ajpheart.00195.2007 (2007). Marik, P. E. Noninvasive cardiac output monitors: a state-of the-art review. Journal of cardiothoracic and vascular anesthesia 27 , 121-134, doi:10.1053/j.jvca.2012.03.022 (2013). Ng, H. W., Walley, T. J. & Mostafa, S. M. Comparison of thermodilution, thoracic electrical bioimpedance and Doppler ultrasound cardiac output measurement. British journal of anaesthesia 73 , 119-120 (1994). Peyton, P. J. & Chong, S. W. Minimally invasive measurement of cardiac output during surgery and critical care: a meta-analysis of accuracy and precision. Anesthesiology 113 , 1220-1235, doi:10.1097/ALN.0b013e3181ee3130 (2010). Squara, P. et al. Noninvasive cardiac output monitoring (NICOM): a clinical validation. Intensive care medicine 33 , 1191-1194, doi:10.1007/s00134-007-0640-0 (2007). Raval, N. Y. et al. Multicenter evaluation of noninvasive cardiac output measurement by bioreactance technique. J Clin Monit Comput 22 , 113-119, doi:10.1007/s10877-008-9112-5 (2008). Rich, J. D., Archer, S. L. & Rich, S. Evaluation Of Noninvasively Measured Cardiac Output In Patients With Pulmonary Hypertension. American journal of respiratory and critical care medicine 183 , A6440, doi:10.1164/ajrccm-conference.2011.183.1_MeetingAbstracts.A6440 (2011). Joosten, A. et al. Accuracy and precision of non-invasive cardiac output monitoring devices in perioperative medicine: a systematic review and meta-analysisdagger. British journal of anaesthesia 118 , 298-310, doi:10.1093/bja/aew461 (2017). Squara, P., Rotcajg, D., Denjean, D., Estagnasie, P. & Brusset, A. Comparison of monitoring performance of Bioreactance vs. pulse contour during lung recruitment maneuvers. Critical care 13 , R125, doi:10.1186/cc7981 (2009). Bland, J. M. & Altman, D. G. Measuring agreement in method comparison studies. Stat Methods Med Res 8 , 135-160, doi:10.1177/096228029900800204 (1999). Huang, L., Critchley, L. A. & Zhang, J. Major Upper Abdominal Surgery Alters the Calibration of Bioreactance Cardiac Output Readings, the NICOM, When Comparisons Are Made Against Suprasternal and Esophageal Doppler Intraoperatively. Anesth Analg 121 , 936-945, doi:10.1213/ANE.0000000000000889 (2015). Montenij, L. J., Buhre, W. F., Jansen, J. R., Kruitwagen, C. L. & de Waal, E. E. Methodology of method comparison studies evaluating the validity of cardiac output monitors: a stepwise approach and checklist. British journal of anaesthesia 116 , 750-758, doi:10.1093/bja/aew094 (2016). Cecconi, M., Rhodes, A., Poloniecki, J., Della Rocca, G. & Grounds, R. M. Bench-to-bedside review: The importance of the precision of the reference technique in method comparison studies – with specific reference to the measurement of cardiac output. Critical Care 13 , 201, doi:10.1186/cc7129 (2009). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 23 Jul, 2025 Reviews received at journal 22 Jul, 2025 Reviews received at journal 14 Jul, 2025 Reviewers agreed at journal 10 Jul, 2025 Reviewers agreed at journal 10 Jul, 2025 Reviewers invited by journal 08 Jul, 2025 Editor assigned by journal 02 Jul, 2025 Editor invited by journal 15 Mar, 2025 Submission checks completed at journal 13 Mar, 2025 First submitted to journal 12 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6214798","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":482213650,"identity":"4a122034-f414-4e94-9dbd-5f90431afcef","order_by":0,"name":"Ludmil Mitrev","email":"data:image/png;base64,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","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":true,"prefix":"","firstName":"Ludmil","middleName":"","lastName":"Mitrev","suffix":""},{"id":482213654,"identity":"c932838f-5abf-42c9-bfed-8de026262dfe","order_by":1,"name":"Michael Rosenbloom","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Rosenbloom","suffix":""},{"id":482213655,"identity":"d1fb9cc4-d5b9-433d-956a-d0e73482fe5a","order_by":2,"name":"Georges Kaddissi","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Georges","middleName":"","lastName":"Kaddissi","suffix":""},{"id":482213656,"identity":"6a5544fc-c81a-4785-92ab-d4d31d396d83","order_by":3,"name":"Ahmed Awad","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Awad","suffix":""},{"id":482213657,"identity":"17143016-ff1b-4c81-9e83-34b2e476a82a","order_by":4,"name":"Janah Aji","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Janah","middleName":"","lastName":"Aji","suffix":""},{"id":482213658,"identity":"420f25e5-9167-4832-967c-1dafdfdc6f73","order_by":5,"name":"Jeffrey Ogbara","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Jeffrey","middleName":"","lastName":"Ogbara","suffix":""},{"id":482213659,"identity":"819796a2-daa5-4f23-be0b-2552dbd96b82","order_by":6,"name":"Keyur Trivedi","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Keyur","middleName":"","lastName":"Trivedi","suffix":""},{"id":482213660,"identity":"e14b487c-1647-469e-9fd7-2e4e16bd9709","order_by":7,"name":"Noud van Helmond","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Noud","middleName":"van","lastName":"Helmond","suffix":""}],"badges":[],"createdAt":"2025-03-12 20:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6214798/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6214798/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-37478-y","type":"published","date":"2026-01-27T15:58:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86667348,"identity":"1696226c-67b3-4839-ba8f-6ede7e4a9722","added_by":"auto","created_at":"2025-07-14 11:15:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":102275,"visible":true,"origin":"","legend":"\u003cp\u003eNormal quantile plot with outlier boxplot of the differences between Cheetah and TD CO measurements.\u003c/p\u003e\n\u003cp\u003eCO, cardiac output; TD, thermodilution.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/0b5d89b6162961586914e2a3.png"},{"id":86667347,"identity":"c11eab58-73ee-40a3-9148-4acd246388c0","added_by":"auto","created_at":"2025-07-14 11:15:28","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":63838,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplot of Cheetah and TD CO measurements.\u003c/p\u003e\n\u003cp\u003eCO, cardiac output; TD, thermodilution.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/8bb697787332a7257904a8f2.jpeg"},{"id":86667349,"identity":"1ce33639-012b-4ba6-9f00-15c126208186","added_by":"auto","created_at":"2025-07-14 11:15:28","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":70900,"visible":true,"origin":"","legend":"\u003cp\u003eDifference plot of Cheetah and TD CO measurements. The dotted line indicates the median difference between Cheetah and TD CO measurements, whereas the dashed lines indicate the 5th and 95th percentiles.\u003c/p\u003e\n\u003cp\u003eCO, cardiac output; TD, thermodilution.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/ad1856e5217b90652360b63c.jpeg"},{"id":86668965,"identity":"4d2c3df0-102c-4bdd-8f3c-80afac66d92e","added_by":"auto","created_at":"2025-07-14 11:23:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":65201,"visible":true,"origin":"","legend":"\u003cp\u003eNormal quantile plot with outlier boxplot of the differences between Fick and TD CO measurements.\u003c/p\u003e\n\u003cp\u003eCO, cardiac output; TD, thermodilution.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/b28b5fb3bfa51a68b738ddad.png"},{"id":86667351,"identity":"e1ac8c97-6dff-4609-8ec1-606e7c3a4ced","added_by":"auto","created_at":"2025-07-14 11:15:28","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":70822,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplot of Fick and TD CO measurements.\u003c/p\u003e\n\u003cp\u003eCO, cardiac output; TD, thermodilution.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/3319a4fef0bbb25131f8b29f.jpeg"},{"id":86668971,"identity":"68b8d02d-6a2a-49b3-8432-c46fec6362ff","added_by":"auto","created_at":"2025-07-14 11:23:29","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":83045,"visible":true,"origin":"","legend":"\u003cp\u003eDifference plot of Fick and TD CO measurements. The dotted line indicates the median difference between Fick and TD CO measurements, whereas the dashed lines indicate the 5th and 95th percentiles.\u003c/p\u003e\n\u003cp\u003eCO, cardiac output; TD, thermodilution.\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/8d3275aaef0ccfdd04bdf5f2.jpeg"},{"id":101691023,"identity":"c22a8119-f560-4f45-9a2b-77650de702b6","added_by":"auto","created_at":"2026-02-02 16:11:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":978852,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6214798/v1/c746cfe9-68ac-4c1b-80a5-9a1da506d9bb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Validation Study Comparing Cheetah Monitor Cardiac Output to Thermodilution Cardiac Output in Patients with Severe Mitral Regurgitation","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe Cheetah monitor (Baxter Healthcare Corporation Inc., Deerfield, IL, USA) is a non-invasive monitor that estimates cardiac output (CO) based on transthoracic bioreactance. It is of practical importance to know the extent to which the CO estimation provided by the device can be used interchangeably with thermodilution CO (TD CO) in patients with significant mitral regurgitation (MR). Cold right heart bolus TD CO is well-established as an accurate and precise method of CO measurement in patients with MR, but a pulmonary artery catheter is not always used in contemporary practice and non-invasive methods that perform with an acceptable degree of accuracy and precision could be useful in the care of patients with MR.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eLeft and right heart catheterization is standard of care in the pre-operative evaluation of patients with severe MR. While left heart catheterization (LHC) assesses peak and mean pressure gradients across the aortic valve, the state of the patient\u0026rsquo;s coronary vasculature, and provides an angiographic assessment of left ventricular performance, right heart catheterization (RHC) can be performed to measure the various pressures from superior vena cava to the pulmonary artery, to obtain mixed venous blood sampling, and estimate CO using the modified Fick method. Since TD CO can be obtained in patients who are undergoing right heart catheterization, the primary aim of this study was to assess the bias and limits of agreement between Cheetah CO and TD CO. A secondary aim was to assess the bias and limits of agreement between Fick CO and TD CO in these patients. TD CO was the method of reference in both cases. The trending ability of the Cheetah monitor was not assessed due to the short procedure time and the lack of significant hemodynamic changes during cardiac catheterization.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eIn total, 26 participants enrolled and completed the study. Similar numbers of women and men participated, and most participants (62%) had severe mitral regurgitation (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Baseline demographic and clinical characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eStudy participants\u003c/p\u003e\n \u003cp\u003e(N = 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eAge in years, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e64.6 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eGender, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e12 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e14 (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eBody mass index in kg/m\u003csup\u003e2\u003c/sup\u003e, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e25.9 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eBody surface area in m\u003csup\u003e2\u003c/sup\u003e, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e1.9 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003eMitral regurgitation severity, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e7 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Moderate/Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e3 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 312px;\"\u003e\n \u003cp\u003e16 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 623px;\"\u003e\n \u003cp\u003eSD, standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMost subjects had no or mild tricuspid regurgitation; only two had moderate tricuspid regurgitation. Two subjects (11%) had severely depressed ejection fraction (EF) and 6 (22%) had moderately depressed EF, with the remained having normal EF. All study subjects were breathing spontaneously and were in steady state during all measurements. They received on average 1.4 milligrams midazolam and 66.4 micrograms fentanyl for conscious sedation during the catheterization procedure.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePrimary Aim\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eDistribution of differences between Cheetah and TD CO measurements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eDifferences between Cheetah and TD CO measurements in a normal-quantile plot followed a non-linear path (Figure 1). A Shapiro-Wilk test indicated a non-normal distribution (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= .038).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCorrelation between Cheetah and TD CO measurements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eSpearman correlation analysis indicated a weak to moderate correlation (\u0026rho; = .393, \u003cem\u003eP\u003c/em\u003e = .048) between Cheetah and TD CO measurements (Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAgreement between Cheetah and TD CO measurements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA difference plot between Cheetah and TD CO measurements indicated poor agreement between Cheetah and TD CO measurements (Figure 3). The median difference between Cheetah and TD CO measurements was 0.86 L/min. The 5\u003csup\u003eth\u003c/sup\u003e and 95\u003csup\u003eth\u003c/sup\u003e centile were -3.34 L/min and 6.01 L/min, respectively. Of all differences, 23.1%, 53.8%, and 46.2% were 0.5 \u0026le; L/min, \u0026le; 1 L/min, and \u0026gt;1 L/min, respectively. There was no evidence of proportional bias (\u0026rho; = -.138, \u003cem\u003eP\u003c/em\u003e \u003cem\u003e=\u0026nbsp;\u003c/em\u003e.496). The repeated precision of the TD reference was 4%, whereas the precision of Cheetah CO measurements was 2%, indicating that differences between measurement techniques were likely not attributable to repeatability variation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSecondary Aim\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eDistribution of differences between Fick and TD CO measurements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eDifferences between Fick and TD CO measurements in a normal-quantile plot followed a non-linear path (Figure 4). A Shapiro-Wilk test indicated a non-normal distribution (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= .017)\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCorrelation between Fick and TD CO measurements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eSpearman correlation analysis indicated a moderate correlation (\u0026rho; = .670, \u003cem\u003eP\u003c/em\u003e \u0026lt; .001) between Fick and TD CO measurements (Figure 5).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAgreement between Fick and TD CO measurements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA difference plot between Fick and TD CO measurements indicated moderate agreement between Fick and TD CO measurements (Figure 6). The median difference between Fick and TD CO measurements was -0.18 L/min. The 5\u003csup\u003eth\u003c/sup\u003e and 95\u003csup\u003eth\u003c/sup\u003e centile were -1.52 L/min and 3.36 L/min, respectively. Of all differences, 45.4%, 63.6%, and 36.4% were 0.5 \u0026le; L/min, \u0026le; 1 L/min, and \u0026gt;1 L/min, respectively. There was no evidence of proportional bias (\u0026rho; = .003, \u003cem\u003eP\u003c/em\u003e \u003cem\u003e= .\u003c/em\u003e984).\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur study found poor agreement between Cheetah and TD CO in patients with moderate to severe MR, and moderate agreement between the modified Fick CO and TD CO. The median difference between Cheetah and TD CO measurements was 0.86 L/min, whereas the median difference between Fick and TD CO measurements was -0.18 L/min. The differences between the measurements were not normally distributed, which could have been the result of a small sample. We therefore did not use classic Bland and Altman limits of agreement of\u0026nbsp;\u0026plusmn;1.96 standard deviations, but\u0026nbsp;a non-parametric equivalent, namely the 5\u003csup\u003eth\u003c/sup\u003e and 95\u003csup\u003eth\u0026nbsp;\u003c/sup\u003ecentiles of the differences between the method of interest and the reference method (Cheetah and Fick CO vs. TD CO, respectively). These limits were wide in the case of Cheetah CO (-3.34 L/min and 6.01 L/min), and less so in the case of Fick CO (-1.52 L/min and 3.36 L/min). In either case, there was no evidence of proportional bias.\u003c/p\u003e\n\u003cp\u003eConsiderable variability exists concerning the biases and limits of agreement of CO monitors relative to a reference method such as TD CO.\u003csup\u003e[3-8]\u003c/sup\u003e Prior studies of Cheetah CO have shown smaller biases and LOA compared to our findings. One study comparing Cheetah CO to a continuous TD CO system in intensive care patients showed that\u0026nbsp;Cheetah CO had a bias of +0.16 L/min and limits of agreement of \u0026plusmn;1.04 L/min.\u003csup\u003e[9]\u003c/sup\u003e Another study in intensive care patients showed a bias of -0.09 L/min and limits of agreement of \u0026plusmn;2.4 L/min.\u003csup\u003e[10]\u003c/sup\u003e Yet another study\u0026nbsp;evaluated Cheetah CO to Fick CO and TD CO in subjects with pulmonary hypertension.\u003csup\u003e[11]\u003c/sup\u003e Bias and limits of agreement of Cheetah CO compared to Fick CO\u003csub\u003e\u0026nbsp;\u003c/sub\u003ewere 0.21\u0026plusmn;2.3 L/min. Bias and limits of agreement of Cheetah CO compared to TD CO were -0.37\u0026plusmn;2.6 L/min. In the same study, the bias and limits of agreement of Fick CO against TD CO were -0.91\u0026plusmn;2.1 L/min.\u003c/p\u003e\n\u003cp\u003eA meta-analysis of studies examining the bias and precision of non-invasive CO monitors found a random-effects pooled bias and limits of agreement of \u0026minus;0.13\u0026thinsp;and 2.23 litres\u0026nbsp;min\u003csup\u003e\u0026minus;1\u003c/sup\u003e, respectively.\u003csup\u003e[12]\u003c/sup\u003e The percentage error was 47%, and there was significant inter-study heterogeneity. However, only one of the studies in this meta-analysis compared the Cheetah CO to a method of reference (partial carbon dioxide rebreathing method).\u003csup\u003e[13]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eWeaknesses of our study include the relatively small sample size and the non-normally distributed data, necessitating the use of non-parametric methods. In their 1999 paper, Bland and Altman pointed out that such methods are \u0026ldquo;generally less reliable than those obtained using normal distribution theory.\u0026rdquo;\u003csup\u003e[14]\u003c/sup\u003e In addition, 11% of patients in our study had severely depressed ejection fraction, raising the possibility of low flow states affecting the measurements. Two subjects had moderate tricuspid regurgitation (TR). This also raises the question of whether their TR could have affected the TD CO measurements.\u003c/p\u003e\n\u003cp\u003eThe bias and the 5\u003csup\u003eth\u003c/sup\u003e and 95\u003csup\u003eth\u0026nbsp;\u003c/sup\u003ecentiles of the differences between Cheetah and TD CO were considerably higher and wider in our study population compared to the results of the other studies of Cheetah CO referenced herewith. We conclude that Cheetah CO cannot be used interchangeably with TD CO in patients with severe MR. An overestimation of CO by almost 1 L/min by the Cheetah monitor would be clinically significant even in subjects with high CO. This is not to say that the Cheetah monitor is not valuable in patients with no MR. Additionally, this study did not evaluate the monitor\u0026rsquo;s trending ability as the RHC and LHC are short procedures and are not usually associated with major hemodynamic changes.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThe Cooper University HealthCare Institutional Review Board (IRB) approved the study (IRB #19-210EX). All procedures were in accordance with the ethical standards of the local IRB and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants in the study provided written informed consent.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eCheetah Non-Invasive Cardiac Output Monitor\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe Cheetah monitor uses bioreactance to estimate cardiac output.\u003csup\u003e[9,10,15]\u003c/sup\u003e The pulsatile flow of blood in the large thoracic arteries produces phase shifts in an alternating current passed through the chest via two pairs of external electrodes, on on either side of the chest above and below the diaphragm.\u003csup\u003e[6]\u003c/sup\u003e The phase shifts are measured, and stroke volume (SV) is estimated based on its correlation with the phase shifts and the thoracic voltage. The Cheetah signal effectively measures the blood volume change in the thorax between systole and diastole. The monitor has been validated in spontaneously breathing and mechanically ventilated patients, as well as in patients with arrhythmias. Unlike bioimpedance, the bioreactance method is independent from the distance between the electrodes.\u003csup\u003e[5]\u003c/sup\u003e Because the electrodes are paired, two separate signals are obtained and averaged to produce the SV estimate.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eInclusion and Exclusion Criteria\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eSubjects were enrolled if they met the following criteria:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.\u0026nbsp; \u0026nbsp;Had planned RHC and LHC\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp;Were at least 18 years of age\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp;Provided written informed consent to participate in the study.\u003c/p\u003e\n\u003cp\u003e4. \u0026nbsp; Had at least moderate to severe MR (echocardiographic grade 3 or 4 MR) on pre-referral transthoracic echo\u003c/p\u003e\n\u003cp\u003e5. \u0026nbsp; The subjects\u0026rsquo; height and weight was accurately documented.\u003c/p\u003e\n\u003cp\u003eSubjects were excluded if the following conditions were present:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eOther valve pathology graded greater than moderate (aortic, tricuspid, pulmonic)\u003c/li\u003e\n \u003cli\u003eDid not have a pre-procedure transthoracic echocardiogram (TTE)\u003c/li\u003e\n \u003cli\u003eChronic atrial fibrillation with irregular pulse\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eIntracardiac shunt\u003c/li\u003e\n \u003cli\u003eIntra-aortic balloon pump or other circulatory assist device\u003c/li\u003e\n \u003cli\u003eIntubated or unconscious patients\u003c/li\u003e\n \u003cli\u003eKnown pregnancy\u003c/li\u003e\n \u003cli\u003eEmergency heart catheterization\u003c/li\u003e\n \u003cli\u003eUncompensated congestive heart failure\u003c/li\u003e\n \u003cli\u003eCurrent participation in an investigational drug or device study that could interfere with the study endpoints\u003c/li\u003e\n \u003cli\u003eAnticipated reason why TD CO could be obtained.\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch2\u003e\u003cstrong\u003eCardiac Output Measurements\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eRHC and LHC was performed using routine methods. Catheterization data were recorded using the McKesson Cardiology Station Release 13.0 (McKesson Corporation, San Francisco, CA). All system clocks were matched and time-stamped data was exported from the Cheetah monitor on a USB drive. A Swan-Ganz catheter was used during RHC to measure TD CO with intermittent cold saline bolus. The TD CO was averaged from 3, 4 or 5 boluses as determined by the interventional cardiologist on visual inspection of the thermodilution curve. The Cheetah CO values were exported from the Cheetah monitor and averaged over the same period during which the TD CO measurements were made. The modified Fick CO was obtained from aortic and mixed venous blood samples using the Fick equation:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1752160417.png\" width=\"214\" height=\"72\"\u003e\u003c/p\u003e\n\u003cp\u003ewhere CO = cardiac output, VO\u003csub\u003e2\u003c/sub\u003e = estimated O\u003csub\u003e2\u003c/sub\u003e consumption, CaO\u003csub\u003e2\u003c/sub\u003e = arterial oxygen content, CvO\u003csub\u003e2\u003c/sub\u003e = venous oxygen content. VO\u003csub\u003e2\u003c/sub\u003e was estimated as 125 millilitres O\u003csub\u003e2\u003c/sub\u003e x Body Surface Area (BSA). The physiologic equation for CaO\u003csub\u003e2\u003c/sub\u003e and CvO\u003csub\u003e2\u003c/sub\u003e was used:\u003c/p\u003e\n\u003cp\u003eOxygen content = 1.36 x Hgb [mg/dl] x SaO\u003csub\u003e2\u003c/sub\u003e or SvO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n\u003cp\u003ewhere SaO\u003csub\u003e2\u003c/sub\u003e = arterial oxygen saturation, SvO\u003csub\u003e2\u003c/sub\u003e = mixed venous oxygen saturation, and Hgb = haemoglobin. Because the estimated rather than the measured VO\u003csub\u003e2\u003c/sub\u003e value was used, we refer to Fick CO as the \u0026ldquo;modified Fick CO\u0026rdquo;.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eBaseline demographic and clinical characteristics were analysed using descriptive statistics. A two-sided \u003cem\u003eP\u003c/em\u003e-value \u0026lt; .05 was considered statistically significant for all analyses. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003ePrimary aim\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA previously published stepwise approach and checklist for CO monitor validation studies were used to compare the Cheetah CO measurements with the reference TD CO measurements.\u003csup\u003e[16]\u003c/sup\u003e Differences between the Cheetah and TD CO measurements were checked for normality using a normal-quantile plot and the Shapiro-Wilk test.\u003csup\u003e[16]\u003c/sup\u003e Considering these assessments indicated that the differences did not follow a normal distribution, non-parametric approaches were used for correlation analysis as well as the difference plot.\u003csup\u003e[14,16]\u003c/sup\u003e As a non-parametric equivalent to limits of agreement, the 5\u003csup\u003eth\u003c/sup\u003e\u0026nbsp; and 95\u003csup\u003eth\u0026nbsp;\u003c/sup\u003ecentiles of the differences between Cheetah and TD CO measurements were calculated.\u003csup\u003e[14]\u003c/sup\u003e Additionally, the proportions of differences between Cheetah and TD CO measurements \u0026le; 0.5 L/min, \u0026le; 1 L/min, and \u0026gt;1L/min were calculated.\u003csup\u003e[14]\u003c/sup\u003e The proportionality of differences between Cheetah and TD CO measurements was assessed by plotting a regression line in the difference plot and Spearman rank order correlation.\u003csup\u003e[16]\u003c/sup\u003e Cheetah and TD CO repeated measurement precision were calculated using the coefficient of error (CE).\u003csup\u003e[16,17]\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSecondary aim\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eDifferences between Fick CO and TD CO measurements were checked for normality using a normal-quantile plot and the Shapiro-Wilk test.\u003csup\u003e[16]\u003c/sup\u003e Considering these assessments indicated that the differences did not follow a normal distribution, non-parametric approaches were used for correlation analysis as well as the difference plot.\u003csup\u003e[14,16]\u003c/sup\u003e As a non-parametric equivalent to limits of agreement, the 5\u003csup\u003eth\u003c/sup\u003e\u0026nbsp; and 95\u003csup\u003eth\u0026nbsp;\u003c/sup\u003ecentiles of the differences between Fick and TD CO measurements were calculated.\u003csup\u003e[14]\u003c/sup\u003e Additionally, the proportions of differences between Fick and TD CO measurements \u0026le; 0.5 L/min, \u0026le; 1 L/min, and \u0026gt;1L/min were calculated.\u003csup\u003e[14]\u003c/sup\u003e The proportionality of differences between Fick and TD CO measurements was assessed by plotting a regression line in the difference plot and Spearman rank order correlation.\u003csup\u003e[16]\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting Interests:\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThis was an investigator-initiated study supported by an unrestricted research grant by Baxter Healthcare Corporation Inc., Deerfield, IL, USA, awarded to Cooper University Healthcare. In addition, Baxter supplied the Cheetah monitor sensors necessary for the measurements. The funder was not involved in the conduct of the research, data interpretation, manuscript drafting, or the decision to publish.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eL.M. and N.v.H. participated in study conception, design, data analysis and manuscript preparation. N.v.H. prepared all figures and tables. L.M., M.R., G.K., A.A., J.A., J.O. and K.T. participated in enrolment, data collection and manuscript editing.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe acknowledge Brian McEniry, CRC, for his outstanding contributions to the data collection and management of this study.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe complete dataset is available on request from the corresponding author by emailing [email protected].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStetz, C. W., Miller, R. G., Kelly, G. E. \u0026amp; Raffin, T. A. Reliability of the thermodilution method in the determination of cardiac output in clinical practice. \u003cem\u003eThe American review of respiratory disease\u003c/em\u003e \u003cstrong\u003e126\u003c/strong\u003e, 1001-1004, doi:10.1164/arrd.1982.126.6.1001 (1982).\u003c/li\u003e\n\u003cli\u003eNishikawa, T. \u0026amp; Dohi, S. Errors in the measurement of cardiac output by thermodilution. \u003cem\u003eCanadian journal of anaesthesia = Journal canadien d\u0026apos;anesthesie\u003c/em\u003e \u003cstrong\u003e40\u003c/strong\u003e, 142-153, doi:10.1007/BF03011312 (1993).\u003c/li\u003e\n\u003cli\u003eDhingra, V. K., Fenwick, J. C., Walley, K. R., Chittock, D. R. \u0026amp; Ronco, J. J. Lack of agreement between thermodilution and fick cardiac output in critically ill patients. \u003cem\u003eChest\u003c/em\u003e \u003cstrong\u003e122\u003c/strong\u003e, 990-997, doi:10.1378/chest.122.3.990 (2002).\u003c/li\u003e\n\u003cli\u003eEspersen, K.\u003cem\u003e et al.\u003c/em\u003e Comparison of cardiac output measurement techniques: thermodilution, Doppler, CO2-rebreathing and the direct Fick method. \u003cem\u003eActa anaesthesiologica Scandinavica\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 245-251 (1995).\u003c/li\u003e\n\u003cli\u003eKeren, H., Burkhoff, D. \u0026amp; Squara, P. Evaluation of a noninvasive continuous cardiac output monitoring system based on thoracic bioreactance. \u003cem\u003eAmerican journal of physiology. Heart and circulatory physiology\u003c/em\u003e \u003cstrong\u003e293\u003c/strong\u003e, H583-589, doi:10.1152/ajpheart.00195.2007 (2007).\u003c/li\u003e\n\u003cli\u003eMarik, P. E. Noninvasive cardiac output monitors: a state-of the-art review. \u003cem\u003eJournal of cardiothoracic and vascular anesthesia\u003c/em\u003e \u003cstrong\u003e27\u003c/strong\u003e, 121-134, doi:10.1053/j.jvca.2012.03.022 (2013).\u003c/li\u003e\n\u003cli\u003eNg, H. W., Walley, T. J. \u0026amp; Mostafa, S. M. Comparison of thermodilution, thoracic electrical bioimpedance and Doppler ultrasound cardiac output measurement. \u003cem\u003eBritish journal of anaesthesia\u003c/em\u003e \u003cstrong\u003e73\u003c/strong\u003e, 119-120 (1994).\u003c/li\u003e\n\u003cli\u003ePeyton, P. J. \u0026amp; Chong, S. W. Minimally invasive measurement of cardiac output during surgery and critical care: a meta-analysis of accuracy and precision. \u003cem\u003eAnesthesiology\u003c/em\u003e \u003cstrong\u003e113\u003c/strong\u003e, 1220-1235, doi:10.1097/ALN.0b013e3181ee3130 (2010).\u003c/li\u003e\n\u003cli\u003eSquara, P.\u003cem\u003e et al.\u003c/em\u003e Noninvasive cardiac output monitoring (NICOM): a clinical validation. \u003cem\u003eIntensive care medicine\u003c/em\u003e \u003cstrong\u003e33\u003c/strong\u003e, 1191-1194, doi:10.1007/s00134-007-0640-0 (2007).\u003c/li\u003e\n\u003cli\u003eRaval, N. Y.\u003cem\u003e et al.\u003c/em\u003e Multicenter evaluation of noninvasive cardiac output measurement by bioreactance technique. \u003cem\u003eJ Clin Monit Comput\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 113-119, doi:10.1007/s10877-008-9112-5 (2008).\u003c/li\u003e\n\u003cli\u003eRich, J. D., Archer, S. L. \u0026amp; Rich, S. Evaluation Of Noninvasively Measured Cardiac Output In Patients With Pulmonary Hypertension. \u003cem\u003eAmerican journal of respiratory and critical care medicine\u003c/em\u003e \u003cstrong\u003e183\u003c/strong\u003e, A6440, doi:10.1164/ajrccm-conference.2011.183.1_MeetingAbstracts.A6440 (2011).\u003c/li\u003e\n\u003cli\u003eJoosten, A.\u003cem\u003e et al.\u003c/em\u003e Accuracy and precision of non-invasive cardiac output monitoring devices in perioperative medicine: a systematic review and meta-analysisdagger. \u003cem\u003eBritish journal of anaesthesia\u003c/em\u003e \u003cstrong\u003e118\u003c/strong\u003e, 298-310, doi:10.1093/bja/aew461 (2017).\u003c/li\u003e\n\u003cli\u003eSquara, P., Rotcajg, D., Denjean, D., Estagnasie, P. \u0026amp; Brusset, A. Comparison of monitoring performance of Bioreactance vs. pulse contour during lung recruitment maneuvers. \u003cem\u003eCritical care\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, R125, doi:10.1186/cc7981 (2009).\u003c/li\u003e\n\u003cli\u003eBland, J. M. \u0026amp; Altman, D. G. Measuring agreement in method comparison studies. \u003cem\u003eStat Methods Med Res\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 135-160, doi:10.1177/096228029900800204 (1999).\u003c/li\u003e\n\u003cli\u003eHuang, L., Critchley, L. A. \u0026amp; Zhang, J. Major Upper Abdominal Surgery Alters the Calibration of Bioreactance Cardiac Output Readings, the NICOM, When Comparisons Are Made Against Suprasternal and Esophageal Doppler Intraoperatively. \u003cem\u003eAnesth Analg\u003c/em\u003e \u003cstrong\u003e121\u003c/strong\u003e, 936-945, doi:10.1213/ANE.0000000000000889 (2015).\u003c/li\u003e\n\u003cli\u003eMontenij, L. J., Buhre, W. F., Jansen, J. R., Kruitwagen, C. L. \u0026amp; de Waal, E. E. Methodology of method comparison studies evaluating the validity of cardiac output monitors: a stepwise approach and checklist. \u003cem\u003eBritish journal of anaesthesia\u003c/em\u003e \u003cstrong\u003e116\u003c/strong\u003e, 750-758, doi:10.1093/bja/aew094 (2016).\u003c/li\u003e\n\u003cli\u003eCecconi, M., Rhodes, A., Poloniecki, J., Della Rocca, G. \u0026amp; Grounds, R. M. Bench-to-bedside review: The importance of the precision of the reference technique in method comparison studies \u0026ndash; with specific reference to the measurement of cardiac output. \u003cem\u003eCritical Care\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 201, doi:10.1186/cc7129 (2009).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"mitral regurgitation, cardiac output, non-invasive cardiac output monitoring, Cheetah monitor","lastPublishedDoi":"10.21203/rs.3.rs-6214798/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6214798/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMonitoring cardiac output (CO) is helpful in the perioperative management of the patient with severe mitral regurgitation (MR). We assessed the accuracy and precision of the Cheetah CO monitor in patients with moderate or severe MR undergoing right and left heart catheterization as part of their pre-operative evaluation for mitral valve surgery. Cheetah CO was obtained concurrently with thermodilution CO (TD CO). Bias data was non-normally distributed; therefore, a non-parametric equivalent to Bland and Altman limits of agreement was used. Additionally, the proportions of differences between the experimental and reference method that were \u0026le;\u0026thinsp;0.5 L/min, \u0026le; 1 L/min, and \u0026gt;\u0026thinsp;1L/min were calculated. Twenty-seven subjects were enrolled and completed the study. The median difference between Cheetah and TD CO measurements was \u0026minus;\u0026thinsp;0.82 L/min, and the 5th and 95th centiles were \u0026minus;\u0026thinsp;6.05 L/min and 3.25 L/min, respectively. Of all differences, 25.9%, 51.9%, and 48.1% were \u0026le;\u0026thinsp;0.5 L/min, \u0026le; 1 L/min, and \u0026gt;\u0026thinsp;1 L/min. No proportional bias was present. We conclude that the Cheetah CO measurements in patients with moderate to severe MR cannot be used interchangeably with TD CO due to a large bias and imprecision.\u003c/p\u003e","manuscriptTitle":"A Validation Study Comparing Cheetah Monitor Cardiac Output to Thermodilution Cardiac Output in Patients with Severe Mitral Regurgitation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 11:15:24","doi":"10.21203/rs.3.rs-6214798/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-23T15:21:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-22T12:36:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-14T19:35:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"694394585555843880581629524931522546","date":"2025-07-10T09:59:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236982087963369884115899252042674735390","date":"2025-07-10T04:14:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-08T07:38:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-02T04:18:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-15T17:38:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-14T02:18:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-12T20:31:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fda7f2a3-f266-44d9-a750-31e638df9abb","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":51199876,"name":"Health sciences/Cardiology"},{"id":51199877,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-02-02T16:08:26+00:00","versionOfRecord":{"articleIdentity":"rs-6214798","link":"https://doi.org/10.1038/s41598-026-37478-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-01-27 15:58:57","publishedOnDateReadable":"January 27th, 2026"},"versionCreatedAt":"2025-07-14 11:15:24","video":"","vorDoi":"10.1038/s41598-026-37478-y","vorDoiUrl":"https://doi.org/10.1038/s41598-026-37478-y","workflowStages":[]},"version":"v1","identity":"rs-6214798","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6214798","identity":"rs-6214798","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}