Reassessing Normative Cardiac Chamber Measurements: A Comparative Study of TTE and TEE Under General Anesthesia.
Conditions: Heart Chambers
Sponsor: Sunnybrook Health Sciences Centre

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Title: Reassessing Normative Cardiac Chamber Measurements: A Comparative Study of TTE 
and TEE under General Anesthesia. 
 
 
Principal Investigator: Dr. Jacobo Moreno Garijo 
Co-Investigators: Dr. Dhabia Al-Merekhi, Dr. Pablo Perez D'Empaire, Dr. Ignacio Erbetta, Alex 
Kiss, Dr. Idan Roifman, Dr. Paul McMullin, Lilia Kaustov. 

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Background 
Transesophageal echocardiography (TEE) has become an indispensable tool in 
managing patients undergoing cardiac surgery or those with significant cardiac conditions, 
particularly given its utility in settings where transthoracic echocardiography (TTE) faces 
limitations, such as during resuscitation or in assessing shock [1, 2]. 
Despite the growing reliance on TEE, the lack of standardized normative values for 
chamber measurements under general anesthesia poses a challenge. Even though its integral 
role, normative values for TEE chamber measurements, essential for accurate diagnosis and 
monitoring, are based on benchmarks set over two decades ago [3]. Cohen et al. established 
normal values for adult TEE measurements, based on a review of studies using single-plane 
TEE. However, this foundational work did not formally compare TEE with TTE [3]. This gap in 
the research has not been adequately addressed in subsequent years. Previous studies have 
often focused on limited chamber assessments and did not account for the altered 
physiological conditions during surgery [4]. 
The reliance on these dated norms without a formal comparative analysis of TTE 
poses significant limitations, particularly as it does not reflect the advancements in imaging 
technology and the evolving understanding of cardiac physiology under various clinical 
conditions. Furthermore, the absence of a comprehensive evaluation across all cardiac 
chambers under conditions that mimic current clinical practices, such as during general 
anesthesia and positive pressure ventilation, highlights a critical knowledge gap. This 
limitation is compounded by the fact that general anesthesia and positive pressure 
ventilation can significantly alter cardiac function, affecting sympathetic tone, venous return, 
and cardiac output, thus potentially influencing measurement results [5, 6]. 

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Given this context, our study seeks to critically reexamine and update the normative 
values for TEE by directly comparing them with TTE measurements in a contemporary cohort 
of patients undergoing cardiac surgery under general anesthesia. By addressing the 
limitations of prior studies and reflecting on current clinical practices, this project aims to 
establish a more relevant and robust foundation for the use of TEE in cardiac assessment 
and monitoring. Our primary objective is to assess the agreement between TTE and TEE 
measurements in terms of chamber dimensions, with a secondary focus on how these 
measurements correlate in patients subjected to the varying physiological conditions 
induced by general anesthesia. 
 
 
Study Design 
Prospective, single-center, observational, longitudinal cohort study evaluating the 
agreement between transthoracic echocardiography (TTE) and intraoperative 
transesophageal echocardiography (TEE) measurements in patients undergoing cardiac 
surgery. 
 
Study Population 
Patients will be recruited from the cardiac surgery patient pool at the Sunnybrook 
Health Sciences Centre, primarily through the anesthesia pre-assessment clinic. After 
obtaining approval from the ethics board, a total of 114 patients will be enrolled, with an 
anticipated recruitment rate of approximately 2-3 patients per week. With Sunnybrook Health 
Sciences Centre handling approximately 810 cardiac cases annually, of which approximately 
80% are for coronary revascularization, this recruitment rate is feasible and will ensure a 

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diverse and representative sample of the cardiac surgery population. 
 
Study Objectives and Hypothesis 
Primary objective: 
To assess the agreement between transthoracic echocardiography (TTE) and intraoperative 
transesophageal echocardiography (TEE) measurements of cardiac chamber dimensions in 
patients undergoing cardiac surgery. 
Secondary objectives: 
• To investigate the correlation between TTE and TEE measurements under varying 
physiological conditions induced by general anesthesia and positive end-expiratory 
pressure (PEEP). General anesthesia combined with positive pressure ventilation (PPV) 
can reduce systolic LV and RV function to levels indicative of dysfunction in a substantial 
proportion of patients without myocardial disease, affecting cardiac function through 
changes in lung volume, venous return, diastolic interactions between the ventricles, 
and intrathoracic pressure. This study will assess how these varying physiological 
conditions influence the agreement between TTE and TEE measurements.  
• To evaluate the impact of different cardiac conditions on the agreement between TTE 
and TEE measurements. Patients with chronic obstructive pulmonary disease (COPD) and 
other cardiac conditions present unique challenges for echocardiographic assessment due 
to their distinct hemodynamic profiles. The effects of PEEP in these conditions include 
alterations in left ventricular preload, afterload, contractility, and ventricular compliance, 
which can unpredictably impact cardiac output. This objective will explore how COPD and 
various other cardiac conditions affect the correlation between TTE and TEE 

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measurements. The specific conditions to be evaluated include hypertension (HTN), 
diabetes mellitus (DM), smoking history, alcohol use, history of atrial fibrillation, history of 
stroke or transient ischemic attack, chronic kidney disease, liver disease, other 
comorbidities, and The New York Heart Association (NYHA) functional classification (I-IV). 
These insights will help determine the applicability of normative values across diverse 
patient populations. 
 
Hypothesis: 
We hypothesize that there will be a correlation level between fair and moderate 
agreement between TTE and TEE measurements of cardiac chamber dimensions in patients 
undergoing cardiac surgery. Additionally, we anticipate that the correlation between TTE 
and TEE measurements will vary due to different physiological conditions induced by 
general anesthesia. Finally, we expect that the agreement between TTE and TEE 
measurements may vary depending on the specific cardiac conditions present in the patient 
population. 
 
Inclusion Criteria: 
• Age ≥ 18, able to provide informed consent. 
• Patients scheduled for coronary revascularization cardiac surgery under general 
anesthesia. 
• With normal left ventricular (LV) systolic function, defined by an ejection fraction of 
50% or more, and normal right ventricular (RV) systolic function. 
• Requiring intraoperative echocardiographic assessment. 

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Exclusion Criteria: 
• Patients with contraindications to either transthoracic echocardiography (TTE) or 
transesophageal echocardiography (TEE). 
• History of poor-quality echocardiography data that preclude accurate assessment. 
• Undergoing emergency cardiac surgery. 
 
Methodology 
Preoperative and postoperative TTE examinations will be performed routinely by 
registered sonographers in the cardiology echocardiography laboratory in awake patients 
within two weeks prior to scheduled surgery. The reported TTE findings will be used as a 
screening tool to include only patients with normal LV and RV function. The TTE images 
obtained will then be measured by two different examiners. 
For both TTE and TEE, measurements will be taken over 3 to 5 consecutive beats. 
End-diastolic measurements will be defined as the R-wave on ECG. End-systolic 
measurements will be defined as the end of the T-wave on ECG. These measurements will 
be normalized to body surface area (BSA) using the Mostellar formula. 
Transthoracic Echocardiography Measurements: 
TTE measurements will follow the ASE chamber quantification guidelines 2015:[7] 
Left Ventricle: 
• The LV linear internal measurements, at end-diastole (LVIDd) and end-systole (LVIDs), 
will be measured in the parasternal long axis view (PLAX) perpendicular to the LV long 
axis at the level of mitral valve leaflet tips.  
• Interventricular septum (IVS) and posterior wall thickness (PWT) will be measured in 

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the same view using M-mode approach.  
• LV mass will be calculated using the linear method formula or 0.8 x (1.04 x [IVSd + 
LVIDd + PWTd)3 - LVIDd3]) + 0.6.  
• LV volumes and ejection fraction will be measured from the apical four- and two-
chamber views, based on biplane method of disks summation.  
• LV area will be measured in the parasternal short axis view (PSAX) at the papillary 
muscle level by tracing the endocardium and excluding the papillary macules.  
• LV fractional area change (FAC) will be calculated using the equation (end-diastolic 
area [EDA] – end-systolic area [ESA]/EDA) x 100. 
Right Ventricle: 
• The RV internal linear measurements will be measured in the RV-focused A4C view 
at end-diastole. Measurements will include basal linear dimension (RVD1), mid-
cavity linear dimension (RVD2), and longitudinal dimension (RVD3). 
• Proximal RV outflow diameter (RVOT prox) will be measured in the PLAX from the 
anterior RV wall to the IVS-aortic junction, or PSAX from the anterior RV wall to the 
aortic valve at end-diastole.  
• Distal RV outflow (RVOT distal) will be measured in the PSAX, proximal to the 
pulmonary valve at end-diastole.
• RV wall thickness will be measured at end-diastole in the subcostal 4C view using M- 
mode.  
• RV area measurements will be obtained from the RV-focused A4C by tracing of EV 
endocardial border.  
• RV systolic function will be assessed using TAPSE and FAC. RV FAC was calculated 
based on the equation (EDA – ESA/EDA) x 100. 

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Left Atrium: 
• LA measurements will include anteroposterior (AP) diameter measured at PSAX and 
PLAX at the aortic valve level at end-systole. Area will be measured in A4C and 
A2C views at end-systole.  
• LA volume will be assessed using the LA Area and Length method in the A4C and 
A2C views, using the formula [0.85 x A4C Area (cm2) x A2C Area (cm2)]/LA Length 
(cm). 
Right Atrium: 
• RA internal linear dimensions will be measured in the A4C view. Major-axis will be 
measured from center of tricuspid annulus to the superior atrial wall. Minor-axis 
will be obtained perpendicular to major-axis by measuring lateral border of right 
atrium to interatrial septum. RA area will be measured in the same view at end-
systole.  
• RA volume will be assessed in the A4C view by the Area-Length method based on 
the formula [0.85 x RA Area (cm2) x RA Length (cm)]/10. 
Aortic Valve: 
• Left ventricular outflow tract (LVOT) will be measured in PLAX at mid-systole 
using inner edge to inner edge convention.  
• Aortic annulus will be measured in PLAX at mid-systole using inner edge to inner 
edge convention.  
• The Sinus of Valsalva, ST junction, and maximal diameter of the proximal 
ascending aorta will be measured in the same view at end-diastole using the 
leading edge to leading edge convention. 

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Transesophageal Echocardiography Measurements: 
Intraoperative TEE studies will be performed as part of routine care by the National 
Board of Echocardiography-certified echocardiographers. Echocardiography images will be 
obtained using commercially available ultrasound machines.  
Left Ventricle: 
• LV internal dimensions will be measured at end-diastole (LVIDd) and end-systole 
(LVIDs) in the transgastric two-chamber (TG 2C) (90°) view perpendicular to the long 
axis of the LV, immediately below the mitral valve and at the mid-papillary muscle 
level.  
• LV end-diastolic area and end-systolic area will be measured in the TG SAX (0°) 
midpapillary view by tracing the LV cavity and excluding the papillary muscles.  
• The LV fractional area change will be calculated using the equation (EDA – ESA/EDA) x 
100. 
• LV end-diastolic and end-systolic volumes will be measured in the TG 2C view (90°) 
using Simpson’s biplane method. LV ejection fraction will be calculated using the 
formula 100 x (end-diastolic volume – end-systolic volume/end-diastolic volume). 
• IVS and PWT measurements will be acquired in the TG SAX (0°) view of LV immediately 
below the mitral valve leaflet at end-diastole using M-mode and leading edge to 
leading edge method.  
• LV mass will be assessed using the linear method formula. 

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Right Ventricle: 
• RV diameters will be measured in the midesophageal four-chamber (ME-4C) (0°) RV 
focused view. Measurements included RV EDA and RV ESA, obtained by tracing the 
endocardial RV at end-diastole and end-systole, and end-diastolic basal (RVD1), mid 
(RVD2), and long-axis (RVD3).  
• RVOT will be measured in the ME RV inflow-outflow view (60-75°) at aortic valve 
and at pulmonary valve. RV wall thickness will be measured at end diastole – using 
M-mode in the ME 4C RV focused view.  
• RV FAC will be calculated using the equation (EDA – ESA/EDA) x 100. 
• Lateral tricuspid annulus anatomic M-mode (AMM TAPSE) will be measured in the 
ME-4C RV focused view by placing the cursor at the lateral tricuspid annulus and 
angling it towards the apex. 
• RV function will be assessed using RV FAC and AMM-TAPSE as these measurements 
had good agreement with TTE based on previous literature [8]. 
Left Atrium: 
• LA AP diameter will be measured from posterior LA wall to aortic annulus in the ME 
SAX (30-45°) and ME LAX (135°) views at level of aortic valve.  
• LA minor axis will be measured in the ME 4C LV focused view at end-systole from the 
lateral wall to the interatrial septum. Major axis will be measured from distance from 
center of the valve of annulus to the center of the superior LA wall. LA area and 
volume will be obtained by the Area-Length method in the LV focused ME 4AC and 
ME 2AC at end-systole. 
Right Atrium: 
• RA minor axis will be measured in the ME 4C RV focused view at end-systole from 

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anterolateral wall to the interatrial septum. Major axis will be measured from 
distance from center of valve of annulus to center of superior RA wall. RA volume 
will be obtained by the Area-Length method in the RV-focused ME-4AC at end-
systole. 
Aortic Valve: 
• LVOT and aortic annulus measured in the ME aortic valve LAX (135°) view at mid-
systole using the inner edge to inner edge method at hinge points of aortic leaflets.  
• Sinus of Valsalva, ST junction, and maximal diameter of proximal ascending aorta will 
be measured from the ME aortic valve LAX (135°) view at end-diastole, using the 
leading edge to leading edge method. 
 
 
 

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Data Collection 
1. Demographic and clinical characteristics: age, gender, weight, height, BMI, COPD, 
HTN, DM, smoking history, alcohol use, history of atrial fibrillation, history of stroke 
or transient ischemic attack, chronic kidney disease, liver disease, peripheral artery 
disease, valvular heart disease, and NYHA functional classification (I-IV). 
2. Cardiac procedure type: CABG, Valve, CABG + valve, redo procedures. 
3. Preoperative and perioperative echocardiographic measurements by TTE following 
established guidelines and protocols. Measurements include cardiac chamber 
dimensions, ventricular function parameters, and valve assessments. 
4. Limited-quality sonographic examinations. 
5. Inter-observer repeatability and intra-observer reproducibility of ultrasound 
measurements (assessed by computing repeatability and reproducibility 
coefficients). 
 
Statistical Analysis 
Descriptive statistics will summarize demographic, clinical, and echocardiographic data. 
Continuous variables will be described using median and interquartile range, and 
dichotomous and polytomous variables were summarized using frequencies. 
Sample size calculation was based on achieving a power of 80%, with an anticipated 
dropout rate of 10%. The correlation between TTE and TEE measurements in previous 
literature ranged between 0.76 and 0.93 [8-11]. Considering a conservative correlation value 
of 0.75, as suggested by prior studies, a sample size of 114 patients was determined to be 
necessary. 

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The primary outcome will be the agreement between TTE and TEE measurements of 
chamber dimensions. Secondary outcomes include correlations between measurements 
under varying physiological conditions induced by general anesthesia. Statistical analysis will 
include descriptive statistics, Bland-Altman analysis, and calculation of Lin’s concordance 
correlation coefficient. Additionally, subgroup analyses will be conducted to assess the 
impact of different cardiac conditions on measurement agreement. 
With the independent measurement by two examiners of fifteen randomized 
echocardiography data sets, blind to each other’s measurements, the interobserver 
variability was calculated. The Bland-Altman (BA) method was applied to assess the 
agreement between observers, providing the level of agreement (LOA) between the two 
measurements and summarizing the agreement graphically [12]. The intraclass correlation 
coefficient (ICC) and its 95% confidence intervals (CIs) were calculated using agreement 
between ratings. The same examiner repeated the measurements in fifteen randomized 
echocardiography date sets measurements to estimate the intraobserver variability. No 
adjustments were made for multiple comparisons. All p-values and 95% confidence intervals 
were 2-sided, with an alpha level of 0.05. 
 
All analyses were conducted using SAS software, Version 9.4 of the SAS System for 
Windows, and R version 3.4.1. 
 
Knowledge Translation 
Dissemination of Findings: The study results will be disseminated through various channels, 
including peer-reviewed publications in cardiology or anesthesia journals, conference 
presentations, and seminars at academic institutions. 
Clinical Guidelines and Practice: The study findings can contribute to the development or 

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refinement of clinical guidelines for echocardiographic assessment in patients undergoing 
cardiac surgery. This may include recommendations for optimizing the agreement between 
transthoracic echocardiography (TTE) and intraoperative transesophageal echocardiography 
(TEE) measurements, as well as guidance on interpreting echocardiographic data under 
varying physiological conditions induced by anesthesia. 
Educational Resources: Educational resources, such as online modules or workshops, can be 
developed for clinicians involved in cardiac surgery and echocardiography training 
programs. These resources can emphasize the importance of accurate echocardiographic 
assessment and provide guidance on best practices based on the study findings. 
Quality Improvement Initiatives: Hospitals and healthcare institutions can use the study 
findings to implement quality improvement initiatives aimed at standardizing 
echocardiographic protocols and enhancing interobserver variability in echocardiographic 
measurements. This may involve training programs, protocol revisions, or the implementation 
of quality assurance measures. 
Collaboration with Stakeholders: Collaboration with key stakeholders, including cardiac 
surgeons, anesthesiologists, echocardiographers, and patient advocacy groups, will facilitate 
the translation of study findings into clinical practice. Engaging stakeholders throughout the 
research process can ensure that the study addresses relevant clinical questions and that 
the findings are effectively disseminated and implemented. 
 
References 
 
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Perioperative Trauma Patient? Curr Anesthesiol Rep. 2022;12:210-6. 
[2] Teran F, Prats MI, Nelson BP, Kessler R, Blaivas M, Peberdy MA, et al. Focused 
Transesophageal Echocardiography During Cardiac Arrest Resuscitation: JACC Review Topic of 

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the Week. J Am Coll Cardiol. 2020;76:745-54. 
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for normal adult transesophageal echocardiographic measurements. J Am Soc Echocardiogr. 
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[4] Skarvan K, Lambert A, Filipovic M, Seeberger M. Reference values for left ventricular 
function in subjects under general anaesthesia and controlled ventilation assessed by two-
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Care. 2005;9:607-21. 
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[7] Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations 
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transesophageal echocardiography in systole and diastole. Eur J Echocardiogr. 2009;10:319-24. 
[11] Kabirdas D, Scridon C, Brenes JC, Hernandez AV, Novaro GM, Asher CR. Accuracy of 
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