Role of Mitral Leaflet Separation Index ( MLSI ) in Determining Mitral Stenosis Severity

Objective. To Correlate MLSI with 3-D mitral valve area (MVA) planimetry in determining mitral stenosis (MS) severity. Background. Mitral Stenosis (MS) is still a major problem in cardiology, and causes of morbidity dan mortality worldwide. Echocardiogrphy plays an important role in assessing mitral stenosis severity. Mitral leaflet separation index (MLSI) is one of simple method that can be used in peripheral by using common ultrasound to assess the severity mitral stenosis. Methods. We employed a cross sectional study. Mitral stenosis patients who referred for evaluation echocardiography in National Cardiac Center Harapan Kita from April to September 2011. MLSI was obtained by averaging the maximal leaflet separation distance at the tips in diastole in parasternal long-axis and apical fourchamber views. 3-Dimensional (3-D) mitral valve area (MVA) planimetry as a reference. The only exclusion criteria was severe calcification and poor echo window. Echocardiography examination using Philips E33i. Results. Seventy six consecutive patients were enrolled, 5 subjects were excluded from study because of severe calcification and poor echo window. Proportion of woman is 73.2 % and mostly in age group < 40 years old (43.7 %). Severe mitral stenosis was dominate the subject, 47 subject (66.2 %), moderate was 19 subject (26.8 %), and mild only 5 subjects (7.0 %). Analysis with Spearman correlations obtained a good correlation with r = 0.70, p < 0.001, good correlation was found in sinus rhythm with r = 0.78, p < 0.001 and atrial fibrillation with r = 0.79, p < 0.001. MLSI less than 0.69 cm predicted severe MS with 85 % sensitivity and 82.4 % specificity. Conclusions. Mitral leaflet separation index (MLSI) has a good correlation with 3-D MVA planimetry. MLSI less than 0.69 cm can estimate severe SM.


Introduction
Background M itral stenosis (MS) is one of the leading cause of morbidity and mortality in the world, especially in developing countries.MS was first reported by Raymond de Vieussens on 1705. 1 In 2003, Euro Heart Survey stated that 12% of all valvular heart disease was MS. 2 To date, Echocardiographic evaluation holds essential role regarding determination of MS Severity, whereas catheterization methods of measurement are slowly being left behind. 3orld Health Organization (WHO) estimated that over 15.6 million people had Rheumatic Heart Disease (RHD).The prevalence of RHD in Southeast Asia was 0.8 per 1000 populations. 4,5In Australia, Carapetis et al found that RHD incidence is declining along as increasing age, but its prevalence remains steadily increase. 6Sliwa et al. in Africa, found that 72% of all valvular heart defects were caused by RHD, and mitral stenosis (MS) is the most common cardiac pathology of RHD. 7 Along with decline in RHD prevalence, nowadays, MS has never been exclusively found as a single valve defect without other valve involvement. 8In the period of 2007-2010, at National Cardiac Center Harapan Kita (NCCHK), the amount of MS cases was about 200 cases a year.
Echocardiography holds an essential role in diagnostic and evaluation of valvular heart disease, and currently the most preferable non-invasive method to determine severity of valve stenosis.Marijon et al. showed that RHD prevalence in Cambodia and Mozambique was 10 times higher when using echocardiography as screening method compared to clinical screening only. 9Reddy et al. also stated that echocardiographic evaluation must be routinely done in order to detect frequently missed features on routine physical examination. 8Determination of stenosis severity using echocardiography is the basis of clinical decision.Because of that, echocardiography is a standard in determining MS severity. 10S severity determination is very important for diagnostic, therapeutic and prognostic purposes.It is used most importantly in choosing between Percutaneus Transvenous Mitral Commisurotomy (PTMC) or surgical approach in dealing with MS cases.The echocardiographic evaluations routinely done were measurement of Mitral Valve Area (MVA) in 2 dimensional or 3 dimensional using methods such as planimetry, pressure half time (PHT); Mitral valve gradient, and systolic pulmonary artery pressure.These methods are routine use in determining severity of mitral stenosis. 11,12However, every method has its own superiorities and flaws.
Mitral Leaflet Separation Index (MLSI) is one of the methods that can be done using common 2-D echocardiography examination.The examination uses parasternal long axis and apical 4 chamber view, and measures width between two tips of mitral leaflet during mid-diastole.In 1979, Fisher et al. was one of the first that discover positive correlation between M-mode MLS and catheterization. 13Seow SC et al. studied 88 MS patients and found significant correlations between MLSI and 2D MVA planimetry (r=0.91;p<0.01) and PHT (r=0.86;p<0.01), similar result was also found in MS patients with atrial fibrillation (r=0.86 and r=0.79; p <0.01). 14Holmin C et al. also find good correlation between MLSI and 2D MVA planimetry in MS patients. 15he rationale of using MLSI method is because of the structure of mitral valve that has 3-dimensional shaped so that the measurement of valve cusp separation with 2-dimensional echocardiography may be more accurate. 15By taking a piece of two fairly orthogonal views, the index can provide substituting images for measuring MVA.Thus, the main advantage of MLSI compared with planimetry lies in its simplicity and ease of making measurements.MLSI is not recommended to replace other tests that have been commonly used in assessing the severity of mitral stenosis, but may be used in addition to these methods. 13ecently, Gorlin's equation that is based on catheterization examination is considered as a standar in the measurement of MVA.However, 3-D MVA planimetry has better correlation when compared with the other echocardiography methods, the homogenous data can be retrieved on any planes, it is possible to cut precisely at the tip of mitral valve, so we can measure the anatomy of mitral valve area accurately.The most optimal measurement of mitral valve area is on the two long axis view along mitral valve is almost perpendicular to each other, which is described by the navigation on the line of intersection.Short-axis cross section is positioned furthest from the tip of mitral valve leaflets, which is this area is the place of planimetry measurement. 16In addition, the assessment of MVA is anatomically useful because it does not depend on the hemodynamic state, unlike the Jurnal Kardiologi Indonesia • Vol.36, No. 4 • Oktober -Desember 2015 measurement of MVA by using other methods. 17he first study that measured MVA by using 3-D echocardiography was performed by Kupferwasser et al. and Chen et al. in which they compared planimetry 3-D and PHT 2D and the Gorlin's equation. 18,19The 3-D transthoracic echocardiography examination also showed accurate result to assess mitral valve area.Sugeng et al. and Zamorano et al. proved that TTE 3-D compared with planimetry, PHT, and PISA 2-D show more accurate results when compared to Gorlin's equation to assess mitral valve area. 20,21ntil now, there are few studies that compare MLSI and other methods of echocardiographic measurement in determine MS severity.Some studies had shown good correlation between MLSI and 2D echo, meanwhile severity evaluation using 3D echo is still not popular.This method can be used for screening purposes in peripheral areas using common ultrasound device.
This research is meant to give input and additional data in determining MS severity.We hope this research can provide a method that is simpler compared to the others, so that it can be used in other centers using common ultrasonogram, and as a valuable screening tools to determine MS severity.

Methods
This is a cross-sectional analytic study.The objective is to find out correlation between 2D MLSI echo cardiography and 3D MVA planimetry.This study took place at Cardiology and Vascular Medicine Department of Faculty of Medicine Universitas Indonesia-National Cardiac Center Harapan Kita, in the period of April 2011-September 2011.The population is all patients that have been diagnosed with MS and underwent echocardiography evaluation in the Imaging and Non Invasive Division, and haven't had surgery prior to the time frame.This study used consecutive sampling.Subject variability will not affect the study because all examination was done in the same time.With no time difference, variability will not be significant.By using consecutive sampling, we were trying to get as much sample as possible.The inclusion criteria all MS patients that have echocardiography examination and the exclusion criteria are echocardiograms that are poor echo window and severe mitral leaflet calcification seen on echocardiogram.
Research Procedure, Echocardiography was done using iE 33 Philips.MLSI was taken at parasternal long axis view and apical 4 chamber view on mid diastolic phase at the time of maximal opening of mitral leaflet, measurement was done from leaflet's inner edge to inner edge, mean value from 3 beats (at Sinus rhythm) and 5 beats (at AF rhythm) was taken. 153D MVA planimetry was done with same device, measuring distance between leaflet tips and taken at apical 4-chamber, 3-chamber or 2-chamber view in mid diastolic. 21ata Analysis, Normality test was using coefficient of variant and data presented as mean values + standard deviation or median values for continuous data.Correlation Spearman test was used with abnormal distribution value, ROC curve was used to determine meeting point of MLSI to predict severe mitral stenosis with MVA 1 cm 2 .Inter and intra observer analysis was using cronbach alfa and intraclass correlation.All data was analyzed using SPSS 11.5.3D MVA planimetry is the effective area of mitral leaflets orifice's at mid diastolic phase using 3D echocardiography, values in cm 2 and MLSI is mean value of distance masured between leaflets of mitral valve in mid diastolic phase, values in cm 14,15 .MS Severity (based on MVA) 10 ; Mild : > 1.5 cm 2 , Moderate : 1.0 -1.5 cm 2 , Severe : <1.0 cm 2

Correlation between MLSI and 3D MVA Planimetry
With Spearman correlation test, we can infer that a strong correlation exist between MLSI and 3D MVA  Receiver operating characteristics curve showed that severe MS with MVA less than 1 cm2 occur if MLSI was less than 0.69 cm, with 85% sensitivity and 82.4% specificity (figure 6.)   Spearman Test, r = 0.78, p < 0.001

Inter and Intra observer variability on MLSI measurement
In this study, efficacy measurement of MLSI method was verified with the first examiner, and the result was appropriate.This can be seen from cronbach α value and intra class correlation level 0.99; meanwhile inter observer variability showed 0.94 (table 5.)

Discussion
At the present time, echocardiography is a gold standard of diagnostic method to determine MS severity. 10,22The methods that are commonly used to determine MVA are 2D planimetry, PHT, CE, PISA, and 3D planimetry, and some indirect method such as mMVG and SPAP.However, all those methods have their own advantages and disadvantages.Spearman test, r = 0.79, p < 0.001 correlations between MLSI and 3D-planimetry on subjects with AF iver operating characteristics curve showed that severe MS with han 1 cm2 occur if MLSI was less than 0.69 cm, with 85% sensitivity pecificity (figure 6.) Spearman test, r = 0.79, p < 0.001  methods, but as an additional method that will strengthen in the determination of severity of mitral stenosis.

Conclusions and Suggestions
MLSI has a good correlation with measurements of MVA using 3-D planimetry, MLSI value less than 0.69 cm can estimate severe mitral stenosis with MVA < 1 cm 2 with sensitivity 85% and specificity 82.4%.We suggest MLSI is expected to become a routine method taken in the echocardiography examination for screening purpose of mitral stenosis patients at peripheral regions, which just have common utrasound equipment.

Table 4 .
Mean values of MLSI and 3D MVA Planimetry in Sinus rhythm and

Table 2 .
Distribution of subjects according on medical risk characteristic (n=71)

Table 4 .
Mean values of MLSI and 3D MVA Planimetry in Sinus rhythm and Atrial Fibrillation subgroup

Table 5 .
interobserver and intraobserver variability in mitral valve assestment with MLSI