Role of Two Dimension Strain and Strain Rate Echocardiography in Assessment of Rheumatic Mitral Valve Stenosis

Introduction: Current echocardiographic parameters have a limitation in assessing mitral valve (MV) apparatus in rheumatic mitral stenosis (MS) patient. In the current study, we use 2 dimensional (2D) longitudinal strain (S) and strain rate (Sr) imaging in evaluating the papillary muscle longitudinal strain (LS) as an objective and quantitative echocardiographic parameter with high reproducibility in the assessment of MV apparatus in patients with mild to moderate rheumatic MS with preserved ejection fraction (EF%). Patients and Method: The study included 40 patients with established diagnosis of MS subdivided in to 31 patients with moderate MS (mean age: 32 ± 5) and 9 patients with mild MS (mean age: 31 ± 6). 20 healthy individuals (mean age 31 ± 6) as a control for cases. The mitral valve area (MVA) was estimated using planimetry and pressure half time (PHT) methods. 2D longitudinal systolic S and Sr imaging was carried out for all participants from the apical long axis (LAX), 4 chamber (4C), 2 chamber (2C) views. Global longitudinal systolic S and Sr were estimated by averaging the 3 apical views. Longitudinal myocardial strain of papillary muscle PMs was assessed by the use of the free strain method from apical 4 chamber view for the antrolateral papillary muscle (APM) and apical long axis view for postromedial papillary muscle (PPM). Results: Patients with MS had significantly decreased longitudinal LV systolic S and Sr


Introduction
Indeed, the commonest pathophysiological etiology of MS is rheumatic heart disease [1]. The most commonly affected valve is MV, and it is markedly influenced where 65% -70% of rheumatic patients suffer from stenosis and/or regurgitation [2]. Chronic affection of the MV leaflets in rheumatic patients in particular with recurrent episodes includes chronic scarring [3].
These valvular changes become progressive over time resulting in funnelshaped stenotic MV. Rheumatic affection of subvalvular apparatus might be in the form of fusion, retraction, thickening, shortening, as well as calcification [3].
In MS, if it is considered that fibrosis mainly involves the valve along with nearby structures such as the papillary muscles APM & PPM, the measurement of longitudinal strain of papillary muscles in addition to the underlying myocardium by 2D strain and Sr is new quantitative method for assessment of MV apparatus.
In fact, echocardiography is considered the primary diagnostic modality for evaluation of MV.
With implementing 2D strain and Sr echocardiography acquire an essential role as a technique that can assess the geometry and function of myocardium in

MS.
Strain (S) is a measure of fiber shortening, and strain rate (Sr) assesses the deformation rate. Thus, both of two methods can give complementary information regarding the global & regional myocardial function [4].

Aim of the Work
To assess MV apparatus along with LV systolic function in patients had mild to moderate MS with preserved EF% via the use of 2D longitudinal systolic strain S and Sr imaging.

Patients and Methods
60 cases were rolled out in this study where 40 patients with established diagnosis subdivided into 2 subgroups 9 patients with mild MS, 31 patients with moderate MS and 20 subjects as a control. The study was approved by the ethics committee of the hospital and all included subjects have consented to participate in this study.
Exclusion criteria 1) Patients suffering from coronary artery disease (CAD) and apparent LV wall motion abnormalities.
2) Patients suffering from LV systolic dysfunction (EF% less than 50%). Each person included in the study was subjected to: 1) Careful history taking and thorough physical examination.
2) Standard 12-lead electrocardiogram (ECG): For the assessment of cardiac rhythm, features suggesting chamber enlargement, and CAD.
Patients were monitored through a single-lead ECG.
The left atrial diameter, LV end-diastolic & end-systolic diameters, LV fractional shortening %, the interventricular septum (IVS) thickness, and the posterior wall (PW) thickness were measured based on the American Society of Echocardiography recommendations [5]. The LV EF was calculated using modified Simpson's biplane method of disks. Traditional MS indices as maximum MV pressure gradient (PG) and mean MV pressure gradient (MG) were estimated. Mitral valve area (MVA) was measured using mitral orifice planimetry in parasternal short axis view, along with the Doppler derived pressure halftime method (PHT) and the average area was estimated using the mean value of 2 measurements. MS severity was measured according to hemodynamic data, using MVA, MG and pulmonary artery systolic pressure (PAP) as follows: mild MS (MVA more than 1.5 cm 2 , MG less than 5 mmHg, or PAP less than 30 mmHg), moderate MS (MVA 1.0 -1.5 cm 2 , MG 5 -10 mmHg, or PAP 30 -50 mmHg), and severe MS (MVA less than 1.0 cm 2 , MG more than 10 mmHg, or PAP > 50 mmHg). PAP was calculated by adding 10 mmHg, considering the diameter of the inferior vena cava (IVC) and level of its collapse that result due to respiration, to the value estimated by evaluating the Bernoulli equation that is simplified from tricuspid insufficiency velocities. The valvular incompetence was assessed by colour flow Doppler imaging. 4) Measurement of the 2D S and Sr: 2D echocardiography images (transmit/receive 1.9/4.0 MHz) were obtained from LV apical long axis, 4 chamber, and 2 chamber views with frame rates of 50 -90 frames/s. Digital data were stored and analyzed off-line. LV endocardial surface was traced manually, and the speckle tracking width was modified in order to cover the whole LV wall thickness so as to obtain curves. Peak LV longitudinal systolic strain (LSS) and Sr (LSSr) were calculated for apical LAX, 4C, and 2C views, and global LV systolic strain (GLSS) and Sr (GLSSr) were calculated through averaging the 3 apical views, Longitudinal myocardial strain of PMs was assessed by the free strain method from apical 4chamber view for APM and apical long axis view for PPM [6].
Patients in whom PM views were clearly visualized in both systole &diastole were considered eligible for the assessment.
In fact, free strain method allows for the measuring of user defined custom local velocities, displacement & deformation using unlimited directional chords World Journal of Cardiovascular Diseases display technique. This work flow measures strain within the myocardial region, free of restraints on the location or direction of the measurements that might be radial, longitudinal or circumferential. Free strain has the advantage of being easy, rapid and practical technique for measurement of myocardial deformation.
This method is especially preferred in the measurement of PMs deformation as these structures are relatively separated from the LV myocardium and aren't included in the commercially available LV strain models [6].
Measurement of the longitudinal strain using the free strain method needs selection of the region of interest by clicking 2 points manually. The 1 st point was chosen from the base of the PM at its attachment zone to the LV wall. The 2 nd one was chosen from the tip of the PM with special attention so as to keep a 3 -5 mm distance from the chordae aiming to avoid artifacts.
All STE acquisitions were carried out at frame rates between 50 -70 Hz frames/second. The average value of S was taken from the 3 consecutive beats.
The peak systolic values were recorded for GCS, GLS and longitudinal S of APM & PPM [6].
All the echocardiographic studies were done by one echocardiographer and for intra-observer variability, a sample of 2D S and Sr measurements was randomly selected and examined by the same observer in 2 different days and intra-class correlation coefficients were calculated for the same observer.

Statistical Analysis
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp) Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution Quantitative data were described using range (minimum and maximum), mean, standard deviation, median and interquartile range (IQR).
Significance of the obtained results was judged at the 5% level. curve allows also a comparison of performance between two tests.

7) Sensitivity
The capacity of the test to correctly identify diseased individuals in a population "TRUE POSITIVES". The greater the sensitivity, the smaller the number of unidentified case "false negatives".

8) Specificity
The capacity of the test to correctly exclude individuals who are free of the disease "TRUE NEGATIVES". The greater the specificity, the fewer "false positives" will be included.

9) Positive Predictive value (PPV)
The probability of the disease being present, among those with positive diagnostic test results.

10) Negative Predictive value (NPV)
The probability that the disease was absent, among those whose diagnostic test results were negative.

Demographic and Conventional Echocardiographic Characteristic
Age & gender indices there was no significance difference between the control group and patients with MS (p > 0.05), heart rate was significantly increased in patients with MS in comparison with the control group (p < 0.001).
There was no significant difference between systolic and diastolic blood pres-

2D S and Sr Measurements
There was a highly significant lower peak LV longitudinal systolic strain (LAX-LSS, 4C-LSS, 2C-LSS and GLSS) in patients with MS in comparison with the control group (<0.001).

Discussion
Rheumatic heart disease is the commonest pathophysiological etiology of MS.
[1] indeed, the rheumatic fever incidence as well as its complications have decreased in developed countries; however, the disease is still considered a major health problem in the vast majority of developing countries. The most commonly & severely affected valve is the MV where about 65% -70% of patients affected by rheumatic process have stenosis and/or regurgitation [2]. Chronic rheumatic invovement of the MV leaflets mainly with recurrent episodes includes chronic scarring [3].
Over time, these changes become progressive leading to funnel-shaped stenotic MV. Rheumatic involvement of subvalvular apparatus might be in the form of fusion, thickening, retraction, shortening, and calcification. As a result, the free interchordal space decreases and the opened "leaflet-chordae tendineae tunnel" available for diastolic flow is reduced [3]. In MS, if it is considered that thods. Gash et al. [7] detected that ejection phase indices are reduced in patients with LV dysfunction in comparison with those who don't have LV dysfunction.
Kurtulus et al. [8] used TDI, Dogan et al. [9] and Simsek et al. [10] used Doppler strain, and Ozdemir et al. [1]  Strain is a measure of fiber shortening, and Sr measures the rate of deformation. Thus, both of these techniques can give complementary data regarding the global & regional myocardial function [4]. TDI-derived strain imaging is highly angle dependent and it measures deformation in one dimension only. On the contrary, 2D strain analysis doesn't have angle limitations, permits deformation analysis in 2 dimensions, decrease intra-observer and inter-observer variability, and consume less time. So, 2D strain imaging can reflect subclinical heart disease, and true wall motion which can't be determined by using the TDI-derived strain analysis [11]. So, in the current study we used 2D S & Sr imaging technique.
Regarding the longitudinal 2D strain we found that the global longitudinal systolic strain was significantly impaired in patients with MS compared with controls (P value ≤ 0.001).
We measure the longitudinal strain of APM and PPM using the free strain method from apical 4C view for (APM) and apical long axis view for (PPM) [6]. It has been determined that the longitudinal strain of APM & PPM was significantly reduced in patients with MS in comparison with normal controls (P value ≤ 0.001).
Our results can be explained by long term sequelae of rheumatic fever, the endocardium and myocardium might be involved with variable degrees that leads to in the loss of normally functioning cardiomyocytes, cardiomyocytes necrosis and replacement by fibrosis & calcification [1]. LV fibers at the subendocardial site are lined up longitudinally and intersects with the mitral annulus, also, the anterior mitral valve leaflet bound to the septum and the fibrous annulus of the heart, thus pathological events which involve the MV can affect the LV also [4].
By the use of electron beam microscopy Lee & Lee [12] revealed variable degrees of ultra-structural pathological changes of LV muscle cells such as the myofibrils, mitochondria, nuclei and other sarcoplasmic elements.
Younan evaluated 50 patients with an established diagnosis of MS (mean age: 32 ± 8 years) and 30 age-matched healthy individuals (mean age 34 ± 7 years).
He measured the MVA using planimetry and PHT methods. He performed 2D  [14]. They revealed decreased S & Sr values in anterior septum and inferior walls and especially in basal segments in contrast to Özdemir et al. [1].
Yildirimtürk [14] was in agreement with our finding regarding global longitudinal systolic strain (GLSS) which is decreased in MS patients, but APM-LS and PPM-LS weren't included in his study.
Regarding Pearson correlation analysis of S and traditional echocardiographic parameters, in our study, there was a positive and significant correlation be- In Ozdemir et al. study [1] neither longitudinal 2D strain nor Sr analysis were correlated with either MVA or transmitral diastolic pressures. He suggested that LV dysfunction in MS may result from the extension of the rheumatic process to the adjacent myocardial tissue and exhibit no correlation with the severity of MS.

Conclusion
Patients with MS and preserved EF% had a decreased 2D longitudinal papillary World Journal of Cardiovascular Diseases muscles free strain APM-LS & PPM-LS in comparison with the control group.
Also they had a decreased 2D longitudinal LV systolic S & Sr when compared to the control group. 2D S & Sr imaging appears to be of value in the assessment of papillary muscles as a part of subvalvular apparatus and useful in determination of subclinical LV systolic dysfunction in patients with MS and preserved EF%.

Recommendation
Assessing 2D free strain of papillary muscles of the MV could help as a quantitative parameter adding value to the traditional Wilkins score in accurately judging the choice of operative intervention.