COMPARISON OF THREE-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY VERSUS TWO-DIMENSIONAL TRANSTHORACIC ECHOCARDIOGRAPHY

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES DEPARTMENT OF CARDIOLOGY

FINAL MASTER THESIS FACULTY OF MEDICINE

AMANE AWAD MOHAMMAD

COMPARISON OF THREE-DIMENSIONAL

TRANSESOPHAGEAL ECHOCARDIOGRAPHY VERSUS

TWO-DIMENSIONAL TRANSTHORACIC ECHOCARDIOGRAPHY

- A FEASIBILITY IN PATIENTS WITH AORTIC STENOSIS

Supervisor: Dr. Vaida Mizariene Kaunas, 2018

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1. SUMMARY

Author: Amane Awad Mohammad, Supervisor: MD Vaida Mizariene. Department of Cardiology, LUHS Kaunas Clinics. Research title: Comparison of three-dimensional transesophageal echocardiography versus two-dimensional transthoracic echocardiography: a feasibility in patients with aortic stenosis. Keywords: 3DTEE, 2D TTE, Aortic root, LVOT, AA, STJ, Area.

Aim of the research: To assess feasibility of aortic root measurements using three-dimensional echocardiographic data sets in patients with aortic stenosis and compare to conventional methods.

Objectives: To compare differences in aortic root measurements using two-dimensional transthoracic echocardiography and three-dimensional transesophageal echocardiography. Secondly, to evaluate the relationship between additional measurements of the aortic sinuses and conventional linear measurements. Thirdly, determine which imaging modality is superior: 2D TTE or 3D TEE. Methodology: 29 patients with normal aortic valve anatomy, were included into this study. QLAB program has been used to assess the aortic root dimensions. 2D TTE aortic root dimensions (left ventricular outflow tract, aortic annulus, sinuses and sinutubular junction diameters) were taken from patient case histories echocardiographic protocols. The area of outflow tract, aortic annulus and sinutubular junction was calculated using formula: Area (cm2_{) =D}2_{x0.785. The data was collected and}

analysed on the SPSS computer program. Comparison of the two different image modalities (3D TEE vs 2D TTE) of the same structure will tell us if there is a difference between the two image modalities. Results: We observed that: aall linear measurement was different significantly, except anteroposterior aortic annulus diameter (p=0.83). All sinus diameters in 3D TEE images were significantly lower to conventional sinus measurement from 2D TTE image (3.490.46cm, p<0.001). Rrelationship between 2D TTE measurement of aortic sinuses and all measurements of sinuses from 3D TEE, showed good and statistically significant correlation between both methods. Bland-Altman analysis for + 2SD whowed that LVOT and AA shows statistically significant difference between 2D TTE and 3D TEE modalities where 2D TTE underestimates the values. However, for STJ, 2D TTE measurements showed overestimation of the value.

Conclusions: Aortic root anatomy evaluation from 3D TEE is feasible in most of cases. 3D TEE image analysis shows higher values of LVOT, higher AA area, but lower values of STJ

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2. SANTRAUKA

Autorius: Amanas Awadas Mohammadas, vadovas: MD Vaida Mizarienė. Kardiologijos katedra, LUHS Kauno klinika. Tyrimai pavadinimas: Palyginimas trimatis transesophageal echokardiografija palyginti dvimatis transtorakalinė echokardiografija: galimybių į paciento su aortos stenozė. Raktiniai žodžiai: 3DTEE, 2D TEE, aortos šaknis, LVOT, A., Stj, plotas.

Tyrimo tikslas: įvertinti Galimybių aortos šaknies matavimų, naudojant trimates echokardiografiniai duomenų rinkinius į paciento su aortos stenozė ir, palyginti su įprastiniais metodais.

Tikslai: Norėdami palyginti skirtumus aortos šaknies matavimų, naudojant dvimatę transtorakalinė echokardiografija ir trimatis transesophageal echokardiografija. Antra, įvertinti santykius tarp papildomų matavimų aortos ančių ir įprastinių linijinių matavimų santykius. Trečia, nustatykite, kuris vaizdavimo būdas yra aukštesnis: 2D TTE arba 3D TEE.

Metodika: 29 pacientai, kuriems buvo normalus aortos vožtuvų anatomija, buvo įtraukti į šį tyrimą. QLAB programa buvo naudojama aortos šaknų matmenims įvertinti. 2D TTE aortos šaknis matmenys (kairiojo skilvelio infundibulinės, aortos žiedo, prienosinių ančių ir sinutubular sankryža diametras) buvo paimti iš paciento ligos istorijos echokardiografiniai protokolų. Ištekėjimo trakto, aortos žiedo ir sinutubular sandūroje plotas buvo apskaičiuojamas pagal formulę: plotas (cm 2) = D2 x0.785. Duomenys buvo patikrinti ir analizuoti SPSS kompiuterio programoje. Palyginimas dviejų skirtingų vaizdų sąlygų (2D vs 3D TEE TTE) iš tos pačios struktūros, mums pasakys, jei yra skirtumas tarp dviejų vaizdų sąlygų.

Rezultatai: Mes pastebėjo, kad: Aall linijinis matavimo buvo labai skirtingas, išskyrus anteroposterior skersmens aortos žiedo (p = 0.83). Visi sine skersmuo 3D TEE vaizdų buvo žymiai mažesnis nei įprastų sine matavimo iš 2D vaizdo TTE (3.49 0.46cm, p <0,001). Rrelationship tarp 2D TTE matavimo aortos ančių ir visų ančių iš 3D TEE matavimai parodė, gerą ir statistiškai reikšminga koreliacija tarp trukdote metodus. Nuobodus Altman analizė +2 SD whowed Tai LVOT ir A. rodo statistiškai reikšmingą skirtumą tarp 2D ir 3D TEE TTE sąlygų kur 2D TTE pagal sąmatas vertes. Tačiau STJ, 2D TTE matavimams, parodė vertės pervertinimą.

Išvados: daugeliu atvejų yra įmanomas aortos šaknų anatomijos vertinimas iš 3D TEE. 3D TEE vaizdo analizė rodo didesnes vertybes LVOT, didesnį AA srityje, tačiau mažesnes vertes Stj matavimus. Be to, linijiniai matavimai aortos ančių rodo, mažesnes vertes, nei standartinio linijinio skersmens, gautų iš dviejų matmenų vaizdo. Dvimatis echokardiografija įvertinimų kairiojo skilvelio ištekėjimo trakto ir aortos Žiedas Ploto matavimas prieš trimatis echokardiografija, o per Įvertinimų sinutubular jungčių matavimo.

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3. ACKNOLEWDGEMENTS

Firstly, I would like to express my sincere gratitude to my supervisor Dr. Vaida Mizariene, for the continuous support in my thesis study and related research, for her patience, motivation, and immense knowledge. Her guidance helped me in all the time of research and writing of this thesis. I could now have imagined having a better supporter, advisor and mentor in my thesis.

Secondly, I would like to express a big thank you to the department of Cardiology in Kaunas Hospital, for allowing me to access their database system, use their facilities and patient record.

4. CONFLICTS OF INTERESTS

The author reports no conflicts of interests.

5. ETHICS CLEARANCE CHANGE THE NAME, LOOK AT MY

FILE

Research title: Comparison of three-dimensional transesophageal echocardiography versus two-dimensional transthoracic echocardiography: a feasibility in patients with aortic stenosis

This research was approved by Center of Bioethics of Lithuanian University of Health Sciences, Kaunas, Lithuania.

Date: …..

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6. ABBREVIATIONS

3D – three – dimensional 2D – two-dimensional AS – aortic stenosis AV – aortic valve AA – aortic annulus

AVR – aortic valve replacement LA – left atrium

LCC – left coronary cusp LV – left ventricle

LVOT – left ventricle outflow tract

MDCT – multidetector computed tomography NCC - non-coronary cusp

RA – right atrium

RCC – right coronary cusp STJ – sinutubular junction

TAVI – transcatheter aortic valve implantation TEE – transesophageal echocardiography TTE – transthoracic echocardiography

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7. INTRODUCTION

Aortic stenosis (AS) is one of the most common primary cardiac valvular diseases and comprises a significant cause of cardiovascular morbidity and mortality 1. Complex 3D anatomy of aortic valve, consisting of left ventricular outflow tract (LVOT), valve cusps, sinuses of Valsava and proximal ascending aorta, impedes/troubles its assessment [2].

The definite management for patients with severe AS is surgical aortic valve replacement. However, in the last few years, transcatheter aortic valve implantation (TAVI) has become an alternative treatment option 3. TAVI is a suture-less, minimally invasive procedure which carries a lot of advantages compared to open heart surgery, especially for the elderly patients and those with prohibitive surgical risks [3].

The safety and efficacy of TAVI procedure are directly related to the imaging modality based on the patient selection and procedural guidance [5]. Proper imaging technique is crucial for assessment of valvular anatomy and, consequently, prevention of post-operative complications [4]. Therefore, the chosen imaging technique has to allow very precise measurements of the complex aortic valve apparatus.

“In-depth understanding of aortic root anatomy has become pivotal over the past few years. Thus, imaging techniques have garnered growing attention because they allow more precise/exact measurements of the annulus and aortic root for proper definition of the spatial orientation of aortic valve complex”. 5

It is essential to provide correct measurements of aortic valve annulus in order to avoid under-sizing and over-under-sizing of the transcatheter heart valves. A complete assessment of anatomy of aortic valve complex is required during pre-procedural decision making. 5

It is important to provide for these patients with a proper imaging modality, hence that’s why a comparison between two-dimensional transthoracic echocardiography (2D TTE) and three-dimensional transesophageal echocardiography (3D TEE) is made in this study.

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8. AIM AND OBJECTIVES

Aim of the research: To assess feasibility of aortic root measurements using three-dimensional echocardiographic data sets in patients with aortic stenosis and compare to conventional methods.

Objectives:

1. To compare differences in aortic root measurements using two-dimensional transthoracic echocardiography and three-dimensional transesophageal echocardiography.

2. To evaluate the relationship between additional measurements of the aortic sinuses and conventional linear measurements.

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9. LITERATURE REVIEW

9.1 Structure and anatomy of aortic root 9.1.1 Normal anatomical variants

The aortic root acts a fundamental stent that surrounds, supports and upholds the 3 aortic cusps. It connects the heart to the systemic circulation. It extends from basal attachments of cusps within the left ventricle (ventriculo-aortic junction that refers to the aortic annulus measured with echocardiography) to their distal attachment at the sinutubular junction (STJ). The crown-like semilunar attachment of the leaflets within the sinuses of Valsalva, 3 interleaflet triangles separate each cusp. 67

Aortic root has 3 main circular rings, planes and crownlike ring that can be recognized, which makes the aortic root a 3D structure. All begin with the aortic valve leaflet that is attached throughout the length of the aortic root. The tightest part of the aortic root is the aortic valve annulus, and by definition, it is a virtual ring with 3 anatomical anchor points at the base of each attachment of aortic leaflets. (Figure 1) 5

It is important to think of the aortic root as one functional unit, distally neighbouring to the aorta and proximally to the ventricle, forming a bridge and whereas all part has to work in synchronization. Rarely a single element is involved in dysfunction unless there is isolated perforation of the leaflet. 8.The location where ventricular structures changes to fibroelastic wall of the arterial trunk, is the anatomic boundary between left ventricle and aorta. However, this location is not coincident with the attachment of the leaflets of the aortic wall. The leaflets are attached within a cylinder and extend to sinutubular junction of the aorta. This semilunar attachment of the leaflets forms a hemodynamically junction between left ventricle and aorta. All structures located distally to these attachments are subject to arterial pressure, however, all parts proximal to the attachments are subject to ventricular pressure. 9

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9.1.1.1 Aortic root

The aortic root is comprised of several distinct entities; the aortic valve leaflets, the leaflet attachments, sinuses of Valsalva, interleaflet trigones, sinotubular junction and the annulus (figure 2). Which makes the aortic root a geometrically complex structure. 10 The root bulges outward to create the three sinuses, from the sinuses two coronary arteries are originated. 8 The aortic root can be divided by the semilunar attachment into supra-valvar and sub-valvar components. Aortic sinuses belong to the supra-valvar components while supporting the sub-valvar components are mainly ventricular but extends to the sinutubular junction. 9

9.1.1.2 Aortic valve leaflets

In total there are 3 three leaflets form the aortic valve and its main function is to seal the valve. The valve leaflets can be divided into parts:

▪ Free margin: Thickened circular node, which provides the coaptation area to the corresponding neighbouring valve leaflets.

▪ “belly” of the leaflet

Figure 1 Normal anatomy of the aortic annulus by Kasel et al.

(A) virtual ring (green line) with 3 anatomical anchoir points at the nadir (green point) of each attachments of the 3 aortic leaflets

(B) LCC = left coronary cusp, NCC = non-coronary cusp, RCC = right coronary cusps. 5

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▪ The basal part of the leaflet, also known as leaflet attachments 10

During the time of valve closure the leaflets fall back into their corresponding sinuses without any possibility to occlude any coronary orifice. The leaflets have two surfaces, one facing aorta and the other facing the ventricle. On the ventricular surface, there is a location of apposition, also named lunule. This location occupies the full width along the free margin. At this location, the leaflet meets the adjacent leaflets during the closure. Nodule is a thickened midportion of the lunule. When the valve is in the closed position, each lunule meet together and separates blood from left ventricular cavity from the aorta. 8

The Leaflet doesn’t just form a physical boundary between the left ventricle and the aorta, but also a hemodynamically junction. Structures located distally to the junction are subject to arterial pressure, however, structures proximally to the junction are subject to ventricular hemodynamic. 10

9.1.1.3 Leaflet attachment

On the location where the leaflet is inserted into the wall of aortic root, they form a crown shaped fibrous structure. This is often named the “annulus”. Falsely the name gives an implication that this structure is circular in contrast to the “crown” shape. The location where the leaflet attachments

Figure 2 Nomenclature of aortic root by J thorac Cardiovasc Surg 2007;133:1226-33.

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9.1.1.4 Sinuses of Valsalva

Sinuses of Valsalva are the three bulges of the aortic wall. From two of the sinuses coronary arteries are originated from and they are named accordingly to the left, right and non-coronary sinus. The sinuses are limited distally by the sinutubular junction and proximally by the attachments of the valve leaflets. The sinus wall is thinner than the native aorta and is mostly made up of aortic wall. 10 Sinuses are largest during time of valve closure, as it serve as a reservoir during ventricular diastole and allows filling of the coronary arteries. 8

9.1.1.5 Interleaflet triangles

Underneath each commissure lies the interleaflet triangles. From a histological point of view, they are thinned aortic wall, however hemodynamically the commissures are extension of the ventricular outflow tract and it reaches the level of sinutubular junction in the area of commissure. 8

9.1.1.6 Sinutubular junction

Sinutubular junction is a location that separates the aortic root from the next coming ascending aorta. This so-called sinutubular junction is made up of the distal part of the sinuses towards the ascending aorta together with the commissure (figure 3). 10

9.1.1.7 Aortic Annulus

The word annulus indicates a circular structure and the aortic annulus does not have a histologically nor anatomical boundary that fits the circular description, this leads to confusion. The leaflets are supported in a crown like fashion, and not in a circular ring. Even though there is the absence of any anatomical or histological distinct circular structure the term “annulus” mainly derives from the fact that this area has the smallest diameter in the blood path between the left ventricle and

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the aorta. This is the position of prosthetic valve sizer and implantation of the prosthetic valve. 10

9.1.2 Anatomical, pathological variants

Structural variation is according to the leaflet numbers, aortic valve can have 1-4 leaflets of different variable sizes. While functional abnormalities are aortic stenosis and aortic regurgitation.

A normal aortic valve should contain three valves, this trileaflet design gives the optimal solution for low resistance valve opening. No other valve configuration can provide these characteristics, for example, a bicuspid aortic, whereas valve dysfunction or degree of stenosis always co-exist depending on the configuration. 10. Bicuspid aortic valve is the most common abnormal variant of aortic root that has two leaflets. According to, Edwards JE. The congenital bicuspid aortic valve. Circulation 1961;23:485–8 and Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol 1970;26:72–83, it is reported that the incidence of bicuspid aortic

valve is 1-2% or 0.9-2.5% in the normal population. 8

As a group, they have a higher incidence of sclerosis or calcification on the leaflet leading them presenting at a younger age with aortic stenosis compared to patients with a normal three-leaflet valve.

The bicuspid valve is not uniform and has different morphological forms. The valves may be almost equal in size, or one leaflet may be larger than the other. Usually, the larger leaflet has a raphe in the middle as a mark where the leaflet should have divided during embryological development. Other variations can be a cleft in one leaflet that suggesting incomplete separation. Calcification of bicuspid valve occurs firstly along the raphe and also on the aortic surface of the other leaflet.

Aortic valve with three-leaflet, tricuspid, often has the minor degree of calcifications and is more common in the elderly population. Degenerative valvar stenosis caused by calcification is more commonly seen in patients over the age of 65 years old. In those cases, commissural fusion is absent/minimal except in those cases where there has been concomitant rheumatic valve disease. Dysplasia of the valvar leaflets is often the cause of stenosis in a tricuspid aortic valve in infants and children.

Unicuspid, unifoliate, aortic valve without commissural is often associated with congenital malformation of the left heart, rarely occurs in isolation. Attachment of the solitary lesion occurs circumferentially like a skirt around the eccentrically situated orifice. The orifice is frequently formed like a keyhole and is mostly centrally located. The valve is without commissure, and usually three

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9.2 Imaging modalities

Patients with severe AS, who cannot undergo aortic valve replacement (AVR) and that is considered inoperable, has an alternative treatment option; Transcatheter aortic valve implantation (TAVI). With increasing use of TAVI procedure there is an increased demand on high quality imaging of aortic valve morphology, proper planning and selection, optimizing the procedure and increasing the successful rates of both TAVI. 11Yet, the measurements prior to a TAVI procedure is rather challenging and there is no ideal modality. 12 With an AVR procedure the surgeon can observe the adaption of the prosthesis to aortic root while suturing, but TAVI does not permit the prediction of interaction between the sutureless before implantation, hence the successful rates of TAVI relies on pre-procedure imaging. 11 5

In order to prevent complications and avoid undersizing and oversizing of prosthesis, its essential to provide correct measurements. Undersizing aortic valve annulus leads to smaller prosthesis which could result in paravalvular regurgitation and valve embolization. Nevertheless, oversizing can lead to under-expansion of the prosthesis, with possible reduced valve durability, conduction disturbances leading to permanent pacemaker insertion, or even annular rupture. Valve sizing has been shown to be one of the strongest prevention measurements of post-procedure preventions. An accurate pre-procedural evaluation of patient candidates for TAVI is a mandatory to select prosthesis size.

Multimodality imaging using transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) and multidetector CT (MDCT) are crucial techniques for the quantification of aortic stenosis, proper patient selection, annular sizing, selection of access-site, as well as for peri-procedural guidance, follow up and recognition of possible transcatheter heart valve (THV) related complications. 12 13

However, echocardiography is the one of the cornerstone pre-procedure and post-procedure evaluation. Both safety and efficacy of transcatheter valve replacement procedure are directly related to proper imaging. 51415. It is important to remember that during the cardiac cycle the geometry of the aortic apparatus changes, hence the importance to standardize the phase in which measurements have been taken. For echocardiography annular measurements are usually taken during mid-systole, the time when the root is at is maximal and most circular.

MDCT is not dependent on the cardiac cycle and can size at any point during the cycle. [16] [17]. MDCT is the method of choice in pre-procedure evaluation of TAVI. [18].

However, in clinical practice prosthesis size is currently mostly based on echocardiography, which is an essential imaging tool for all patients that are undergoing TAVI. Size of aortic valve

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TAVI preoperative evaluation requires diagnosing and quantify the degree of AS, sizing of the annulus and surrounding structure (figure 4) to determine the optimal prosthesis type and to determine the adequacy of the peripheral vasculature for selection of an access strategy. [19]

According to Lang et al. [add reference number] Aortic measurements should be made at the following sites; aortic valve annulus, maximal diameter of sinuses of Valsalva, sinutubular junction and maximal diameter of the proximal ascending aorta. [7]

9.2.1 Transthoracic echocardiography (TTE)

TTE remains the mainstay of diagnosis of AS, it gives detailed anatomical and functional assessment, description of heart chamber dimensions, transaortic gradient, velocity and aortic valve area are all determined by TTE, but also gives information about ventricular and valvular morphology (bicuspid vs tricuspid, as its highly relevant as TAVR is still controversial in bicuspid valve) It establishes the presence of AS and its severity. TAVI is indicated in patients with severe AS

Figure 1 Aortic measurements

1. aortic valve annulus, 2. Maximal diameter of sinuses of Valsalva, 3. Sinutubular junction and 4. Maximal diameter of proximal ascending aorta.

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valvulopathies. Nevertheless, if there is presence of acoustic window constrains TTE is not suitable in those cases and TEE might be useful and specially for the assessment of aortic valve planimetry. [20]

TTE is readily available, entails no patient discomfort, and is risk free.

However, it is highly user dependent and in certain patient populations, such as the obese, those with severe emphysematous lung disease, and those with prior thoracic surgery, imaging may be suboptimal. [19] [21] Another reported problem with TTE is underestimation of aortic annulus size measurements, as aortic annulus is widely acknowledged as a virtual ring, its however not fully circular. [13]

9.2.2 Transesophageal echocardiography (TEE)

According to the guidelines of the American Society of Echocardiography and the consensus document on TAVI, its recommended to perform TEE before a TAVI if there is issues regarding aortic root anatomy, aortic valve annular diameter, or the number or cusps.

TEE comes in both 2D and 3D, however 2D TEE is no longer accepted as the sole imaging tool for transcatheter sizing. As previously mentioned, 2D TTE is the first step to asses patients with severe AS. [5]

According to Kasel et al. a direct comparison of TTE and TEE has suggested that systolic sagittal plane measurements on TEE are approximately 1mm larger than on TTE, but this difference is more likely to be the result of image quality rather from differences in techniques.

TEE might also be used in cases when computer tomography angiography (CTA) is contraindicated, example in cases with renal insufficiency. TEE can measure several of the parameters assessed with cardiac CTA, although due to the scalloped nature of the aortic annulus, evidence suggest that TEE might undersize it relative to CTA. [19]

TEE limitations include software is not available on all echocardiographic platforms, visualization of the anterior portion of annulus can be obscured by echo “dropout” due to annular calcification. Furthermore, if there is calcification at the level of annulus, this may hamper the ability to determine boundary definition and might make shape irregular, plane formed by the nadirs of the 3 cusps is often not orthogonal to the LVOT or aortic root and lastly the spatial and temporal resolution of 3D echo is currently limited. Important to remember that echo is operator dependent and may be difficult at many times, even in the experienced hands. [7]

Both TTE and TEE can and have been used for determination of annular dimensions, although they frequently result in underestimation due to the assumption of a circular annulus. They

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10. RESEARH METHODOLOGY AND METHODS

10.1 Research Sample selection

29 patients (17 males and 12 females) were included into this study. All patients had normal aortic valve (trileaflet) anatomy, various degrees of aortic stenosis and positive history of arterial hypertension.

These patients underwent investigation in both a 2D transthoracic echocardiography and 3D transesophageal echocardiography during years of 2016-2018 at Hospital of Lithuanian University of Health Sciences (HLUHS), Cardiology Department, where collection of data and images was made.

10.2 Aortic root measurements 10.2.1 3D TEE

In order to assess the aortic root dimensions in 3D TEE images the program QLAB (Phillips Ultrasound, USA) has been used. The echocardiographic images were saved in 3D zoom images. We choose Q-analysis option, here 3D image is displayed in three orthogonal planes: sagittal, transversal and coronal. After adjusting all three planes, the aortic root is visualized in long axis view, transversal view. LVOT and aortic annulus were measured during systole, when it’s the maximal opening of the aortic valve. While sinuses, STJ and ascending aorta were measured during diastole, cardiac cycle was optimised on ECG.

Aortic annulus was measured at the basal attachment of aortic valve cusps after adjustment of all three planes in correct position. In short axis view (SAX) (transversal plane) anteroposterior, transversal diameters and area of the aortic annulus were measured. In the same manner LVOT was measured approximately within 0.5-1 cm below aortic valve annulus (figure 5). Sinutubular junction measurements (anteroposterior ant transversal diameters and area) were measured after correction of all orthogonal planes immediately above the aortic sinuses. Sinuses of Valsalva are the widest part in the aortic root. After correction all three planes in correct position at the tip of aortic cusps coaptation, measurements were taken from cusp to cusp and from cusp to opposite commissure (figure 6). Anatomical knowledge of nearby area is important in order to find the correct cusp. Non-coronary cusp (NCC), is located near the interatrial septum, right-coronary cusp (RCC), adjacent to right ventricle outflow tract (RVOT) and right atrium. Left-coronary cusp (LCC) is adjacent to left atrium.

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Figure 5. Example of 3D TEE measurements at the left ventricular outflow tract level: green

window - sagittal view; red window - transverse view; blue window - coronal view; D1 – anteroposterior diameter; D2 – transverse diameter; A – outflow tract area;

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10.2.2 2D TTE

2D TTE aortic root dimensions (left ventricular outflow tract, aortic annulus, sinuses and sinutubular junction diameters) were taken from patient case histories echocardiographic protocols. Missed measurements in protocol were done using stored echocardiographic images in databases and measurement were made according current recommendations [7].

The area of outflow tract, aortic annulus and sinutubular junction was calculated using formula:

Area (cm2_{) =D}2_x0.785.

(D – anteroposterior diameter of outflow tract or annulus or sinotubular junction)

10.3 Statistical analysis

The data was collected and analysed on the SPSS computer program. Comparison of the two different image modalities (3D TEE vs 2D TTE) of the same structure will tell us if there is a difference between the two image modalities. Continuous variables are presented as mean ± standard deviation, categorical variables are presented as percentages (%). The tests that are used to assess normality of data distribution is Kolmogorov-Smirnov test and Shapiro Wilk test. Both Student t-test for paired samples and Pearson correlation were used for comparison of measurements. While error and bias between two methods Bland-Altmann analysis was used.

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11. RESULTS

11.1 Demographic data

Patient population (n=29), 12 females (41.4 %) and 17 males (58.6%) were included into the study (Figure 7) Patient age was between 44-80 years old,( 64  10 years old) (Figure 8).

Female patients were older (70.5  8 years) than male (60.4  10), p=0.007, and lower height (164.0  3.8 cm) compared to males (178.7  7 cm), p<0.001.

Figure 7: Gender distribution

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11.2 Aortic root measurements

Aortic annulus, left ventricular outflow tract and sinutubular junction linear measurement and area values from both methods are shown in table 1. All measurement was different significantly, except anteroposterior aortic annulus diameter (p=0.83). The values of aortic sinuses measurements are presented in 2 table. All sinus diameters in 3D TEE images were significantly lower to conventional sinus measurement from 2D TTE image (3.490.46cm, p<0.001).

Table 1: Means and standard deviation (SD) for 3D TEE and 2D TTE measurements

Value 3D TEE measurements 2D TTE measurements P value LVOT diametera_, cm 2.760.27 2.280.26 < 0.001 LVOT diameterb_, cm 2.610.46 2.280.26 < 0.001 AA diametera_,cm _2.270.27 _2.280.26 _0. 83 AA diameterb_,cm 2.510.45 2.280.26 0. 003 STJ diametera_{, cm} _2.790.40 _3.170.39 _< 0.001 STJ diameterb_{, cm} _2.670.47 _3.170.39 _< 0.001 LVOT area, cm2 _4.551.27 _4.110.95 _0. 01 Aortic annulus area,cm2 4.561.21 4.120.93 0. 03 STJ area, cm2 _5.901.64 _7.752.35 _< 0.001 LVOT – left ventricular outflow tract; STJ – sinotubular junction; AA – aortic annulus;

a_{Anteroposterior diameter of annulus or outflow tract was used for comparison from 3D TEE image against} conventional anteroposterior diameter of annulus or outflow tract from 2D TTE

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Table 2. Means and standard deviation (SD) for 3D TEE measurements of aortic sinuses

Aortic sinus measurement 3D TEE measurements

NCC to commisure,cm 2.560.49 LCC to commisure,cm 2.770.46 RCC to commisure,cm 2.660.55 NCC to LCC, cm 2.950.44 NCC to RCC, cm 2.820.54 LCC to RCC, cm 2.820.43

NCC – non-coronary cusp; LCC – left coronary cusp; RCC – right coronary cusp;

Correlation analysis applied to evaluate relationship between conventional 2D TTE measurement of aortic sinuses and all measurements of sinuses from 3D TEE, showed good and statistically significant correlation between both methods. The strongest positive relationship was between 2D TTE sinus diameter and sinus diameter LCC to RCC in 3D TEE (figure 9).

Figure 9: Correlation in sinus measurements between conventional measurement of aortic

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11.3 Comparison of the methods

Correlation between LVOT area measured by 2D TTE and 3D TEE is shown in figure 10 and Bland-Altman analysis for + 2SD for quality control in figure 11. Middle red line indicates mean of values, upper red line represents + 2 SD, and lower red line represents -2SD. Mean difference of LVOT area is -0.44  0.94 (p=0.043;) shows statistically significant difference between 2D TTE and 3D TEE modalities where 2D TTE underestimates the values.

Correlation between AA area measured by 2D TTE and 3D TEE and Bland-Altman analysis for + 2SD for quality control are shown in figures 12 and 13. Mean difference of AA is -0.431  1.28 (p=0.03). This shows measurement underestimation in 2D TTE.

Correlation between STJ area measured by 2D TTE and 3D TEE and Bland-Altman analysis for + 2SD for quality control are shown in figures 14 and 15. Mean difference of STJ is 1.85  2.85 (p<0.001). For this measurement 2D TTE showed overestimation of the value.

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Figure 11: Bland-Altman analysis between 2D LVOT and 3D LVOT. Graph displays

difference of values (Y-axis) against the average values (x-axis) between 2D LVOT and 3D LVOT. Middle line represents mean of the differences

Figure 12: Linear regression analysis between 2D TTE AA and 3D TEE AA

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Figure 13: Bland-Altman analysis between 2D TTE AA and 3D TEE AA.

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12. DISCUSSION OF RESULTS

In this study we analyzed sample consisting of 29 patients with AS: their aortic root was measured with both 3D TEE and 2D TTE imaging modalities. While trying to compare these two different imaging techniques by measuring area of different aortic root dimensions, we observed that: all linear measurement was different significantly, except anteroposterior aortic annulus diameter (p=0.83). All sinus diameters in 3D TEE images were significantly lower to conventional sinus measurement from 2D TTE image (3.490.46cm, p<0.001). Rrelationship between 2D TTE measurement of aortic sinuses and all measurements of sinuses from 3D TEE, showed good and statistically significant correlation between both methods. The strongest positive relationship was between 2D TTE sinus diameter and sinus diameter LCC to RCC in 3D TEE.

Bland-Altman analysis for + 2SD. Mean difference of LVOT area is -0.44  0.94 (p=0.043;) shows statistically significant difference between 2D TTE and 3D TEE modalities where 2D TTE underestimates the values. Mean difference of AA is -0.431  1.28 (p=0.03). This shows also an underestimation in 2D TTE. However, for STJ mean difference of STJ is 1.85  2.85 (p<0.001). For this measurement 2D TTE showed overestimation of the value.

In a study done by Jander et al. [26] (n=244) were LVOT area were compared between TEE, TTE and CT, LVOT diameter measured by TTE (339 ± 62 mm²) was smaller than the one derived from TEE (354 ± 65 mm²; P < .001). Similar results were shown in AVA [26]. This study shows that there is a difference between TTE and TEE. All aortic sinus diameters measured from 3D images were lower than measured from 2D images. Usually conventional measurement of aortic sinuses in 2D TTE image in some cases can be complicated as it is not absolutely clear which coronary cusp is crossed during scanning at the posterior part of the aortic root – left coronary cusp or non-coronary cusp. Using 3D data sets it is completely clear which sinus of the aorta is in the measurement.

Results indicates that 3D TEE is a more reliable and suitable image modality compared to 2D TTE and gives more precise areas in the aortic root. Bland-Altman analysis shows statistically significant difference between 2D TTE and 3D TEE in LVOT, aortic annulus and sinotubular junction measurement. Successful rates of TAVI are directly related to measurements of aortic root prior to procedure. Complications like paravalvular regurgitation can be minimized correct and precise

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p<0.00001) and quality control plots using Altman and Bland method showed no trend for underestimation or overestimation using TTE (mean difference is 0.22 mm; limits of agreement -1.73 – 2.16). The absolute difference between methods was 0.6 ± 0.8 mm. TTE and TEE in this study did not differ.

Study limitation: There were several limitations to this study.

First of all, paucity of the area and space has limited the effort of collecting a larger sample size (n=29). We can conclude that the results are not reliable and not sufficient to be able to extrapolate the statistically analysis in the overall population (AS patients).

Secondly, Echocardiography limitation: According to protocols, it is gold standard that measured data from TTE and TEE should be compared with CT. however, data from TTE and TEE were not compared to CT.

It’s really important to acknowledge the fact that ultrasound quality is operative dependent and in this study 3D images where measured by one person only and that could have biased the study.

13. CONCLUSION

1. Aortic root anatomy evaluation from 3D TEE echocardiographic images is feasible in most of cases. 3D TEE image analysis shows higher values of left ventricular outflow tract, higher aortic annulus area, but lower values of sinutubular junction measurements.

2. Additional linear measurements of aortic sinuses shows lower values than standard linear diameter obtained from two-dimensional imaging.

3. Two-dimensional echocardiography underestimates left ventricular outflow tract and aortic annulus area measurement against three-dimensional echocardiography, while overestimates in sinutubular junction measurement.

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