4Dimensional XStrain Echocardiography: M-Mode and Tissue Doppler Estimation of Age and Gender Specific Normative Values of Aortic Stiffness in Healthy Adults During Covid-19 Pandemic

Research Article | DOI: https://doi.org/10.31579/2692-9759/098

4Dimensional XStrain Echocardiography: M-Mode and Tissue Doppler Estimation of Age and Gender Specific Normative Values of Aortic Stiffness in Healthy Adults During Covid-19 Pandemic

  • Akhil Mehrotra

Prakash Heart Station and Diagnostics Lucknow, India.

*Corresponding Author: Akhil Mehrotra, Prakash Heart Station and Diagnostics Lucknow, India.

Citation: Akhil Mehrotra, (2023), 4Dimensional XStrain Echocardiography: M-mode and Tissue Doppler Estimation of Age and Gender Specific Normative Values of Aortic Stiffness in Healthy Adults During Covid-19 Pandemic, Cardiology Research and Reports. 5(3); DOI:10.31579/2692-9759/098

Copyright: © 2023, Akhil Mehrotra. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 21 April 2023 | Accepted: 05 May 2023 | Published: 12 May 2023

Keywords: aortic stiffness; aortic elasticity; 4d x strain echocardiography; TDI of aorta; healthy adults; Covid-19 pandemic

Abstract

Background: The elastic properties of the aorta are modified in numerous cardiovascular and non-cardiovascular diseases. Multiple studies have evaluated aortic stiffness in myriads of disease state, albeit only few Indian studies have estimated the normal values of aortic stiffness in healthy population.

Objective: To the best of our knowledge, till date no research has been undertaken to determine the age and gender specific value ranges of aortic stiffness parameters in healthy subjects. Hence, in the present study we endeavored to estimate these values in our distinctive study groups of healthy adults.

Methodology: This was a prospective observational study in which 58 healthy adults were enrolled during the turbulent corona pandemic. Study group was of the age group 18-60 years of either sex and was arbitrarily divided into six groups. Exhaustive M-mode and Tissue doppler Imaging was performed by 4Dimensional XStrain echocardiography system for extensive evaluation of multiple M-mode and Tissue Doppler imaging derived parameters of Aortic stiffness and superior wall velocities of ascending aorta.

Result: AOS, AOD, Aortic strain, and elasticity modulus were greater in males. On the contrary Aortic superior wall velocities (SAO, EAO, and AAO) were higher in females. Increasing age lead to a decline in majority of stiffness parameters derived by M-mode echocardiography. Correspondingly EAO determined by TDI of superior wall of aorta, showed a deterioration with advancing age.

Conclusion: The authors report a normal range of M-mode and TDI derived values of Aortic stiffness of ascending aorta, in healthy Indian adults. Difference in magnitude of aortic elasticity indices has been demonstrated in men and women, as well as in different subsets of the study group.

Introduction

Functional sproperties of the aorta are major determinants of normal cardiovascular (CV) function [1].  Increments in aortic stiffness and reduction in aortic distensibility (indicators of elastic properties of aorta) are associated with coronary artery disease [2, 3]. Aortic elasticity is an established methodology for risk stratification of atherosclerotic heart disease, myocardial infarction, stroke and heart failure [3]. 

Numerous methods have been employed for the evaluation of aortic elasticity, namely magnetic resonance imaging (MRI), aortic angiography applantation tonometry, velocity vector imaging, and gated radionuclide angiography [4-8]. Moreover M-mode and Tissue Doppler Imaging (TDI) of the ascending aorta is also used to estimate its elastic properties [9-14]. 

The elastic properties of the aorta are modified in numerous CV and non-cv diseases. Hypertension, mitral valve prolapses, aortic aneurysms, coronary artery disease and heart failure, being the major cv disease and cystic fibrosis, pregnancy, chronic kidney disease, hypothyroidism, sarcoidosis, αl-antitrypsin deficiency and diabetes, being the non-cv diseases, altering the aortic stiffness properties [15-24]. 

Even though aortic stiffness has been evaluated in myriads of disease states, in contrast only few Indian studies have assessed the normal values of aortic stiffness parameters in healthy population [25, 26]. Till date, no research has been undertaken to determine the age and gender specific value ranges of aortic stiffness parameters in healthy subjects. Hence, in the present study we endeavored, to determine the above-mentioned normative values in our distinctive study groups of healthy population.

Material and Methods

This study was carried out at Prakash Heart Station and Diagnostic centre, Lucknow, India. This was prospective, observational study in which 258 healthy Indian adults were recruited, and later on, 200 cases were omitted due to inferior image quality. Finally, 58 participants were enrolled during a period of 9 months from September 2021 to May 2022. Study group was of the age group 18-60 years of either sex, and was arbitrarily divided into six groups:

  • Group A- Overall study population subjects from 18-30 years of age.
  • Group B- Overall study population subjects from 31-60 years of age.
  • Group C- Male subjects from 18-30 years of age
  • Group D- Female subjects from 18-30 years of age
  • Group E- Male subjects from 31-60 years of age
  • Group F- Female subjects from 31-60 years of age

Those participant were included, if they were asymptomatic with a normal physical examination BMI-23 or less, waist size 85 cm2 or less in men and 80 cm2 or less in women, free from overt cardiovascular disease, not receiving any drugs, nonsmoker, nontobacco chewer, nondiabetic, non-hypertensive according to JNC-8 guidelines, having normal thyroid and lipid profile, normal resting electrocardiogram (ECG) in sinus rhythm with a normal two-dimensional echocardiography and Treadmill Stress ECG. Those individuals were excluded if there was presence of diabetes mellitus, neurological or psychiatric illness, malignancy, CAD, Aortic root abnormalities and aortic dilatation thyroid disease, valvular heart disease, history of cardiac rhythm abnormalities, heart failure, systemic hypertension, and significant pulmonary hypertension.

The study procedure was approved by the Institutional Ethics Board of Prakash Heart Station and Diagnostic, Lucknow, India. All subjects or their guardians gave their written informed consent prior to data collection and furthermore confidentiality of patient information was maintained.

Data collection and study procedure     

 All patients underwent full history taking, clinical examination, and a standard resting 12-lead ECG. A negative Covid-19 reverse transcription polymerase chain reaction report conducted within 72 h prior to the data of enrollment and echocardiography, was the essential requirement because the study was conducted during the raging Covid-19 pandemic.

Biochemical and Hormonal Assessment

After 12 h of overnight fasting, blood samples were withdrawn for HBAIC, T3T4TSH, Serum creatinine, Total cholesterol, Triglycerides, low-density cholesterol and high-density cholesterol. These estimations were done to rule out the presence of diabetes mellitus, hypothyroid or hyperthyroid state, renal failure, and dyslipidemia.

Blood pressure measurement

Blood pressure (BP) levels were measured from the right brachial artery at the level of the heart with a mercury sphygmomanometer after resting for at least 5 minutes in the supine position. Three measurements, at least 2-minute apart, were performed, and the average of the closet two readings was recorded. A pressure drop rate of approximately 2 mm Hg/S was applied, and Korotkoff ’s phases I and V were used for systolic and diastolic BP (SBP and DBP, respectively) levels. All BP measurements were made by a cardiologist. Pulse pressure (PP) was calculated as systolic minus diastolic BP.

Echocardiography

All echocardiographic evaluations were performed by the author, using- My Lab X7 4D X Strain echocardiography machine, Esaote, Italy. The images were acquired using a harmonic variable frequency (1-5 MHz) electronic single-crystal array transducer with the subject lying in left lateral decubitus position.

Conventional Echocardiography

M-mode, 2-Dimensional and pulsed wave doppler (PWD) echocardiography was performed from parasternal long-axis, short-axis and apical 3 chamber, 4 chamber and 2 chamber views and the following data were derived: Interventricular septum thickness in diastolic and systolic (IVSD and IVSs respectively), left ventricular posterior wall thickness in diastole and systole (LVPWD and LVPWs, respectively), left ventricular end-diastole and end systole volumes (LVEDV and LVESV, respectively). Moreover, 2-Dimensional ejection fraction (2D-EF Percentage) by biplane Simpson’s method, LV mass in diastole (LV Mass d) and cardiac out-put (CO) were also determined. Cardiac Index was calculated by dividing the CO by body surface area (BSA). By using PWD, early diastolic velocity (E), late diastolic velocity (A), and E/A ratio was measured.

Aortic stiffness assessment by M-mode echocardiography of Ascending Aorta

Systolic and diastolic inner diameter of ascending aorta were recorded by M-Mode echocardiography 3 cm above the aorta valve in a parasternal long-axis image. Aorta systolic diameter (AOS) was measured at the maximum anterior motion of the aorta, and aorta diastolic diameter (AOD) was measured at the peak of QRS complex on the recorded ECG. (Figure 1, 2). All the parameters were computed and the average of 5 consecutive cycles were calculated.

Figure 1: Measurement of aortic diameter obtained at 3 cm above the aortic cusps.

Figure 2: Aorta visualized on M- mode. The movement of aortic wall appears as two wavy lines. The space between the two lines is the aortic lumen. Systolic and diastolic diameters are measured on M- mode.

Aortic distensibility (D), aortic stiffness index (SI) and other elasticity parameters were determined by using the following formulas [27, 28].

  1. aortic Distensibility = 2x AOS–AOD/[(SBP–DBP) X AOD (106. cm2 dyn-1)]
  2. Aortic Stiffness Index = ln (SBP/DBP)/ [AOS – AOD]/AOD] (pure number), ln = natural logarithm
  3. Aortic Pulsatile Change (APC) = AOS – AOD (cm)
  4. Aortic Systolic index (ASysI)
  5. Aortic Diastolic Index (ADI)
  6. Aortic pulsatile index (API)

ASysI, ADI and API were calculated by dividing AOS, AOD and APC by body surface area (BSA), respectively

  1. Aortic compliance (AS) = (AOS-AOD/SBP-DBP) (cm/mmHg)
  2. Elasticity Modulus (EM) = (SBP-DBP)/([AOS-AOD]/AOD) (Pa)
  3. Aortic strain (AS) = (SAO - AOD) X100/ AOD (Percentage) 

Tissue Doppler imaging of Ascending Aorta

Aortic upper-wall velocities were measured by Tissue Doppler Imaging (TDI) at the same point as in the M-mode measurements (Figure 3) gain and filter were adjusted to optimize the image. High temporal resolution (Greater than100 frames/s) and a sweep speed set to 100 mm/s were used. The TDI of expansion peak velocity during systole (SAO) and early (EAO) and late (AAO) contraction peak velocities during diastole were obtained with a 1-mm sample volume size.

Figure 3: Tissue Doppler Imaging of the ascending aorta. The measurements were made at a level of 3 cm above the aortic cusps, at the same point as that for M-mode echocardiography.

The resulting velocities were recorded for 5 consecutive cardiac cycles and stored for later playback and analysis.

Following data were estimated by TDI of the superior wall of ascending aorta (Figure 4).

Figure 4: Aortic superior wall velocity measurements with tissue doppler imaging. SAO, systolic superior wall velocity, EAO, early diastolic superior wall velocity, AAO, late diastolic superior wall velocity.

  1. SAO- Aortic superior wall velocity in systole was calculated at the same point used in M-mode measurement.
  2. EAO- Early diastolic velocity
  3. AAO- Late diastole velocity

Tissue Doppler Echocardiography of left ventricle 

TDI of LV was conducted by placing the PWD sample volume at the lateral mitral annulus in apical four-chamber view, and early diastolic velocity (E’) and E/E’ ratio was determined in the TDI mode.

Four-dimensional XStrain speckle-tracking echocardiography

From the apical position, two-dimensional cine loops were acquired from two-chamber, three-chamber, and four-chamber views. High-quality ECG signal was must for proper gating, and a minimum of three cardiac cycles were acquired of each cine loop. The study was performed with a frame rate between 40 and75 fps and then stored digitally on a hard disk for offline analysis by software package XStrainTM advanced technology TOMTEC GMGH 3D/4D rendering Beutel TM computation capabilities (Figure 5) [29].

Figure 5: X Strain 4D global LV analysis. At the end of each scanning section, the three apical views are acquired. Then, after left ventricular (LV) endocardial border tracking, the software analyzes LV regional deformation parameters. Finally, the Beutel 3D reconstruction allows quantification of global LV function (global longitudinal strain (GLS)—ejection fraction). X Strain TM 4D.

The LV endocardial and epicardial borders were identified, tracked, and highlighted by a semiautomatic tool-AHS Aided Heart segmentation Esaote, for border segmentation. Thirteen equidistant tracking points were automatically incorporated along the LV endocardial border and where necessary manual adjustment of endocardial tracing was done. The software automatically divided the LV wall into 6 segments and them the acquired cine loop of each apical view was tracked frame by frame throughout the entire cardiac cycle. The cine loops with inadequate tracing quality and with any signs of arrhythmia were excluded.

The LV bull’s eye depiction according to 17-segment model was generated by XStrain 4D software, by integrating the results of each set of cine loops [30, 31]. XStrain-4D software created a 3D reconstruction for calculating LV volumes and EF [32], and XStrain 4D-EF by the “Beutel Mode” method (TOMTEC, Germany) (Figure 6) [33].

Figure 6: XStrain 4D software created a 3D reconstruction for calculating LV volumes and XStain 4D-EF by the “Beutel Mode” method (TOMTEC, Germany).

XStain 4D-EF by the “Beutel Mode” method (TOMTEC, Germany).

The following 4D XStrain estimated values of volumetric values were statistically analyzed.

  • Volumetric data: Sphericity index in diastole and systole, LVEDV, LVESV, 4D-EFPercentage, and CO.

Statistical Analysis

Statistical analysis was performed with the Microsoft excel® (Excel 2019.Microsoft corp. Seattle Washington. USA). The continuous variables are expressed as mean ± SD. The 95Percentage confidence interval of mean was also calculated. Enrolled participants were stratified according to Groups A-F, age: Less than 30 years and Greater than 31 years and gender: male and female. Comparison of various datasets between men and women and between different age groups was performed by Students t-test for independent groups.

The level of significance used was Less than0.05. A higher t value having a probability Less than0.05 was marked significant. A p value Less than0.01 was marked highly significant. 

Result

We performed Aortic stiffness assessment of ascending aorta in 58 healthy Indian adults of age 18-60 years mean 32.16±11.82 years, free from overt cardiovascular disease (Table 1). The study population was arbitrarily divided into six groups: Group A from 18-30 years of age, Group B from 31-60 years of age, Group C, male subjects of 18-30 years, Group D, female subjects of 18-30 years, Group E, male subjects of 31-60 years and Group F, female participants of 31-60 years.

NS=Not Significant (p Greater than0.05), ** Highly Significant=(p Less than0.01), * Significant=(p Less than0.05)

Demographic data

The mean BSA of the participants was 1.67±0.18 sq. meter. There were 38 males and 20 females with a mean age of 30.53±12.22 years and 35.25±10.61 years respectively, and a mean BSA of 1.72±0.16 sq. meter and 1.57±0.18 sq. meter respectively (Table 1). The mean age in Group A-E was 23.13±4.33 years, 42.52±8.71 years, 21.68±3.95 years, 26.66±3.08 years, 42.68±8.61 years and 42.27±9.25 years respectively and mean BSA was 1.64±0.17m2, 1.40±0.2m2, 1.67±0.14m2, 1.56±0.18m2, 1.78±0.16m2, 1.56±0.17m2, respectively (Table 2).

NS=Not Significant (p Greater than0.05), ** Highly Significant= (p Less than0.01), * Significant= (p Less than0.05)

Group A: overall subjects (age18-30 years), Group B: overall subjects (age 30-60 years) Group C: Male Subjects (age 18-30yrs),

Group D: Female Subjects-(age 18-30yrs), Group E: Male Subject-(age 31-60yrs), Group F: Female Subjects-(age 31-60yrs)

Conventional Echocardiography Data

LA size, E/A ratio, Lateral TDI E’ and Lateral TDI E/E’ ratio are surrogate measurements for assessment of diastolic function of LV and LVIDd, LVEDV, EPSS and EFPercentage are representative of systolic function. In our study LA size, E/A ratio, lateral TDI E’, LVIDd and LVEDV were significantly higher in males (pLess than0.01) even though CO & 2D-EFPercentage was higher in females (pLess than0.01) (Table 3). Additionally E/A ratio and 2D-EFPercentage were lower in Group B when compared with Group A (pLess than0.01), suggesting a reduction in diastolic & systolic function of LV, with increasing age.

EPSS, E point septal separation, IVSd, interventrciualr septum in daistole, LVPwD, Left ventricualr posterior wall in diastole, LVID, left ventricular, internal dimension LVEDV, Left ventricular end-diastole volume, CO, cardiac output, TDI, Tissue doppler imaging, EF, ejection fraction

NS=Not Significant(p Greater than0.05), ** Highly Significant=(p Less than0.01), * Significant=(p Less than0.05)

Group A: overall subjects (age18-30 years), Group B: overall subjects (age 30-60 years)

4. Dimensional Volumetric Data

The sphericity index in diastole and systole, LVEDV and LVESV were higher in males (pLess than0.01). Nevertheless, 4D-EFPercentage was more in female (pLess than0.01) (Table 4). We noticed a decline in sphericity indices in Group B as compared to Group A (pLess than0.05), suggesting a significant change in LV geometry with increasing age.

LVEDV, Left ventricular end-diastolic volume,LVESV,Left ventricular end-systolic volume,EF,ejection fraction,CO,cardiac output

NS=Not Significant(pGreater than0.05),** Highly Significant=(pLess than0.01),* Significant=(pLess than0.05)

Group A: overall subjects (age18-30 years), Group B: overall subjects (age 30-60 years)

M-Mode data of Aortic stiffness

AOS, AOD, Pulsatile change, Pulsatile index, Aortic Strain and Elasticity Modulus were greater in males (pLess than0.01), and Aortic distensibility was insignificant elevated (p=NS). On the contrary, Aortic Systolic index, Aortic diastolic index was higher in females (pLess than0.01) (Table 5). s

Furthermore, Pulsatile change, Pulsatile index, Aortic Strain were lower in Group B as compared to Group A (PLess than0.01), demonstrating a decline of these stiffness parameters with increasing age.

AOS, Aortic dimension in systole, AOD, Aortic dimension in diastole, Ao, Aorta

NS=Not Significant(p Greater than0.05),** Highly Significant=(p Less than0.01),* Significant=(p Less than0.05)

Group A: overall subjects (age18-30 years), Group B: overall subjects (age 30-60 years)

Tissue Doppler imaging data of Aortic stiffness

SAO, EAO and AAO were higher in females (pLess than0.01) (Table 6). It was also observed that EAO was lower in Group B, indicating a deterioration of in early diastolic upper wall velocity with aging. Contrarily SAO and AAO showed insignificant (p=NS) increment with increasing age.

TDI, Tissue doppler imaging, SAO, Systolic upper velocity, EAO, Early Diatolic aortic upper wall velocity, AAO, late diastolic upper wall velocity

NS=Not Significant(p Greater than0.05),** Highly Significant=(p Less than0.01),* Significant=(p Less than0.05)

Group A: overall subjects (age18-30 years), Group B: overall subjects (age 30-60 years)

Comparison of Aortic stiffness data in various subjects

On comparing Group C and D (male and female subjects of age 18-30 years), it was shown that AOS, AOD, and Aortic Stiffness Index and Elasticity modulus were greater in males of 18-30 years of age (p Less than0.01), even though Aortic Strain was higher in females (p Less than0.01) (Table 7). Similarly, SAO, AAO and EAO reflected a lower value in Group D than Group C, indicating diminished aortic superior wall velocities in female subjects of age 18-30 years of age.

AOS, Aortic dimension in systole, AOD, Aortic dimension in diastole, Ao, Aorta TDI, Tissue doppler imaging, SAO, Systolic upper velocity, EAO, Early diastolic, aortic upper wall velocity, AAO, late diastolic upper wall velocity, Ao, Aortic

NS=Not Significant(p Greater than0.05),** Highly Significant=(p Less than0.01),* Significant=(p Less than0.05)

Group C: Male Subjects (age 18-30yrs), Group D: Female Subjects-(age 18-30yrs), Group E: Male Subjects-(age 31-60yrs), Group F: Female Subjects-(age 31-60yrs)

In addition, when we analysed the data of Group E and F (male and female subjects of age 31-60 years), it was noted that AOS, AOD and Aortic strain values were higher in Group E than Group F. Conversely, the SAO, AAO and EAO values were more in Group F, even though insignificantly (p=NS).

Interestingly, only Aortic strain was lower in Group E when compared to Group C (P Less than0.01), implying that aortic strain was deteriorating with increasing age in male subjects (Table 8). On the contrary AOS, AOD, Aortic stiffness index and Elasticity modulus were insignificantly higher is Group E (p=NS). We also observed that SAO values were higher and EAO values were lower in Group E (p Less than0.01), on comparing with Group C.

AOS, Aortic dimension in systole, AOD, Aortic dimension in diastole, Ao, Aorta TDI, Tissue doppler imaging, SAO, Systolic upper velocity, EAO, Early diastolic aortic, upper wall velocity, AAO, late diastolic upper wall velocity, Ao, Aortic

NS=Not Significant(p Greater than0.05), ** Highly Significant=(p Less than0.01), * Significant=(p Less than0.05)

Group C: Male Subjects (age 18-30yrs), Group D: Female Subjects-(age 18-30yrs), Group E: Male Subjects-(age 31-60yrs), Group F: Female Subjects-(age 31-60yrs)

Subsequently, on collating the Aortic stiffness data in female subjects (Group D and F) we found higher values of AOS, AOD, Aortic Stiffness Index and Elasticity modulus in Group F than D (p Less than0.05, p Less than0.05, p Less than0.01, p Less than0.05), suggesting that in female adults that there is decline in these stiffness parameters with advancing age. Simultaneously SAO and EAO were also higher in Group F (p Less than0.05).

We have extensively estimated the Age and Gender specific values of Aortic Stiffness in various subsets of our study population. Here we are furnishing a summarized values (Table 9) of the above-mentioned parameters discerned from the current study. This table is particularly meant for contemporary and prospective medical researchers to conceptualize further on these interesting original findings.

Discussion

It is well known that increased aortic stiffness has been associated with impaired LV systolic and diastolic functions. The association between increased stiffness and LV systolic dysfunction, has been demonstrated in a previous study [34], particularly along the long axis. The relation is often attributed to increased hemodynamic load caused by stiffer arteries [35, 36]. An alternative explanation for the observed relation between aortic stiffness and LV systolic function, is the direct mechanical ventricular-vascular coupling.

Systolic contraction shortens the LV long axis by pulling the aortic annulus and Sino-tubular junction of the aorta towards the LV apex, which moves minimally during systole [37-40]. The combination of aortic annulus displacement along with sparse movement of the aortic arch implies that there is substantial longitudinal stretch of the ascending aorta during systole [40-42]. 

Abhayaratna et al [43] assessed the relationship of arterial stiffness with LV diastolic dysfunction in 188 elderly individuals and found a significant correlation between central pulse pressure and severity of diastolic dysfunction and concluded that increased arterial stiffness was associated with more severe left ventricular diastolic dysfunction.

Arterial stiffness index establishes the elastic properties of the arterial wall, in a manner relatively independent of blood pressure, and aortic distensibility evaluates the ability of the arteries to dilate during the cardiac cycle [44-51].

Aortic stiffness and aortic distensibility have been examined with VVI and pulse wave velocity (PWV) [46, 52]. However, VVI is a new and invasive method, requiring transesophageal echocardiography, which limits its routine use in clinical practice. Also, PWV is not the ideal procedure to evaluate aortic elasticity properties since it is affected by many factors including hematological and physiological characteristics, as well as heart rate and blood pressure variations [53-55]. 

Direct measurements of aortic elasticity by TDI, which is a practical method for the measurements of diameter changes related to wall movements, may provide further help than other methods described above, because it is not affected by hematological and cardiovascular physiology [56-58]. Multiple articles have shown a link between loss of elasticity in major arteries and cardiovascular adverse events [57, 58]. In the Framingham Cardiology study, over 20 years of monitoring, increased pulse pressure, which is an indication of large vessel wall stiffness has been shown to increase coronary artery disease risk in the middle and older age group, who had no clinical coronary artery disease [59].

Hence the, determination of normal value ranges of Aortic stiffness parameters is imperative, because then only the normal values can be compared to the values obtained in different disease states. 

A considerable amount of literature is available on the adverse impact caused by various disease states on the aortic stiffness parameters, nevertheless, it is exceptionally rare to find a study depicting these values in healthy population. After a deep search of the literature, we could only come across a solitary study [25] which has recently endeavored to put forward the normal values ranges of Aortic stiffness properties in healthy population by 2Dimensional and 4Dimensional XStrain Echocardiography. There were 72 healthy participants in the 2Dimensional group and 30 individuals in the 4D XStrain group. The results are analogous to the current study, even though there were small number of subjects in 4D XStrain group.

In the study of elasticity properties of ascending aorta in healthy children and adolescents [60] 165 subjects were enrolled with a mean age of 11.92±4.0 years. The mean age in our study group was 32.16±11.82 years and to compare their data with the present study would not be feasible. Another research study investigated the effects of subclinical hypothyroidism on elastic properties of the ascending [17]. This study had a strict inclusion criterion and they recruited 48 healthy controls with a mean age of 42±11 years. The values of their control group are incongruous with our study and the reason seems to be the disparity of mean age of the controls of their study and the healthy subjects of the present study. Correspondingly Vitarelli et al [14] reported in their 80 healthy controls, two-dimensional M-mode and TDI guided ascending aorta wall stiffness parameters. The mean age was 49±17 years and the values of stiffness index (SI), Aortic distensibility (D), elastic modulus (EM), SEO, AAO and EAO reflected gross incongruity with our study group. The divergence of results may be because of dissimilarities in the mean age of our study group and their control group (mean age 49±17 years).

Gungor et al [15] showed that aortic stiffness is increased in patients with premature coronary artery disease (CAD). In their study there were 50 patients of acute coronary (ACS) and 70 age sex matched controls. However, in their control groups there were 26 smokers and several were having hypertension, diabetes and hyperlipidemia controlled on medication. Nevertheless, the mean age in their study group was 34±3.9 years which is similar to our study. Since this study included, in their control group volunteers who were current smokers, controlled hypertensives, diabetics and hyperlipidemic therefore to collate the results of aortic stiffness in their control group with our study would not be meaningful.

Earlier studies mentioned above are in some way or the other, inharmonious with the present research work. We have extensively compared our data in healthy population by constructing various subsets of groups and then collating the values amongst them, in a judicious manner. The main results of our study can be outlined as follows: (i) we provided exhaustive data on several parameters of Aortic stiffness determined by M-mode and TDI echocardiography. (ii) Our study group was arbitrarily divided into six groups A-E (iii) 4Dimensional  volumetric data : sphericity index, LVEDV and LVESV were higher in males and importantly, 4D-EF was more in females (iv) AOS, AOD, Aortic strain, and elasticity modulus were greater in males (v) On the contrary Aortic superior wall velocities (SAO, EAO, AAO) were higher in females (vi) Increasing age lead to a decline in parameters of sphericity index, and majority of stiffness parameters derived by M-mode echocardiography (vii) correspondingly EAO determined by TDI of superior wall of aorta, showed a deterioration with advancing age.

Study Limitations

The echocardiographic method of determining the aortic stiffness using mathematical equations may have some limitations [56,57]. Firstly, blood pressure and pulse pressure measured at the level of brachial artery may not exactly reflect aortic pulse pressure and secondly, blood pressure measurement and aortic echocardiographic assessment cannot be carried out simultaneously. All the participants are of Indian ethnicity and the normal value ranges of the present study cannot be anticipated to be identical with other ethnic groups, particularly Caucasians.

Our study had modest number of subjects, because it was undertaken during the raging corona pandemic and to encounter a normal healthy subject during this period was an arduous task. Moreover, this is a single center experience.

Recommendations and future research directions

The authors recommend, in future large scale multiple centers randomized controlled trials for enrolling hundreds of healthy subjects to further investigate the important properties of Aortic stiffness.

Conclusion

The authors report normal range of M-mode and TDI derived values of Aortic stiffness of ascending aorta, in healthy Indian adults. Difference in magnitude of aortic elasticity indices has been demonstrated in men and women, as well as in different subsets of the study group.

References

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Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

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Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

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Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

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Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

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Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

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Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga