Study of Left Atrial Appendage Function in Patients of Severe Rheumatic Mitral Stenosis and Effect of Successful PTMC on SEC Grading

Background: Left Atrial Appendage (LAA) dysfunction is common in patients of Mitral stenosis (MS). In the present study we compared the LAA function amongst patients of severe rheumatic MS with particular reference to spontaneous echo contrast (SEC) and evaluated the effect of successful Percutaneous Transvenous Mitral Commissurotomy (PTMC) on SEC grading. Methods: It was a single centre prospective descriptive type of study. Total 75 cases were included during the study period from 2016 to 2020. Symptomatic patients with severe rheumatic mitral stenosis (MVA<1.5cm 2 ) in sinus rhythm fulfilling the elective PTMC intervention criteria and those who had a successful intervention only were included. All the patients underwent Clinical examination, ECG, detailed TTE and TEE before, Immediately after (within 24hrs) & after 6 months of PTMC. Results: In the present study mean LAAAC% and LAA PW Doppler velocities were significantly less in patients of severe rheumatic Mitral Stenosis having SEC than patients without SEC, implying more severe LAA dysfunction in patients with SEC. LAA Tissue Doppler velocities were also less in patients with SEC compared to patients without SEC but it was statistically not significant. There was a significant negative correlation between SEC grading and LAAAC (%) and LAA PW Doppler velocities (LAAEDE Velocity, LAALDE Velocity and LAAF velocity), i.e. greater the degree of SEC lesser was the LAAAC (%), LAAEDE Velocity, LAALDE Velocity and LAAF velocity, suggesting more severe LAA dysfunction in patients with greater degree of SEC. There was also negative correlation between SEC grading and LAA Tissue Doppler velocities (ELAA Velocity, ALAA Velocity, SLAA Velocity) but it was statistically not significant. Successful PTMC resulted in significant decrease in SEC grading. Conclusion: Among the patients of severe rheumatic mitral stenosis, presence of SEC implies severe LAA dysfunction, greater the intensity of SEC, greater would be the severity of LAA dysfunction and successful PTMC results in improvement of SEC grading.


Introduction
Although mitral stenosis is now rare in developed countries, it has been recognised for more than 300 years. Vieussens described the disease in 1705 and has provided major milestones in cardiology. It was the first disease to be diagnosed with echocardiography, and the first valve lesion to be successfully treated by surgery or percutaneous balloon valvuloplasty.
For suitable valve Percutaneous Transvenous Mitral Commissurotomy (PTMC) is safe and effective treatment for rheumatic mitral Stenosis with results similar to surgical valvotomy [1].
Contrary to earlier belief, the Left Atrial Appendage (LAA) is now thought to play an important role in normal cardiac hemodynamics. The appendage, being more compliant than LA, acts as a reservoir to attenuate the rise in intra-atrial pressure in response to various hemodynamic factors [2]. LAA is a highly contractile muscular sac that obliterates its apex during atrial systole. In Mitral Stenosis (MS) due to chronic pressure and volume overload there occurs gradual left atrial (LA) and Left Atrial Appendage (LAA) dilatation and dysfunction leading to reduced blood flow velocities which predisposes to thrombus formation and thromboembolic episodes [3]. Hence in patients of MS study of LAA emptying and filling velocities are helpful in predicting the risk of thrombus formation. Echocardiography, particularly transesophageal echocardiography (TEE), is currently the modality of choice for evaluation of the LAA [4]. In addition to delineation of thrombus, TEE is helpful in detection of LAA spontaneous echo contrast (SEC). SEC is a smoke-like swirling pattern seen on two-dimensional imaging, it indicates the presence of blood stagnation and is a precursor of thrombus formation [5]. In this study we compared the LAA function in patients of severe rheumatic MS with and without SEC and correlated degree of SEC with LAA function and evaluated the effect of PTMC on SEC grading.

Methods
It was a single centre prospective descriptive type of study. Total 75 cases were included during the study period from 2016 to 2020.

Inclusion Criteria
Symptomatic patients with severe rheumatic mitral stenosis (MVA<1.5cm 2 ) in sinus rhythm fulfilling the elective PTMC intervention criteria and those who had a successful intervention only were included. Successful PTMC was defined as patients who had MVA>1.5cm 2 without increase in MR more than grade 1 and LA mean pressure less than 18 mmHg in absence of complications.

LAA Fractional Area Change% [6]
LAA maximal and minimal areas are obtained by tracing the entire endocardial border of LAA at end diastole and end systole respectively by correlating with ECG. LAA fractional area change percentage (LAAAC%) is calculated according to the formula: x 100

LAA PW Doppler Velocity [4]
LAA PW Doppler velocities were obtained by keeping the sample volume in the middle third of LAA cavity without wall artifacts as shown in figure 2.

LAA Tissue Doppler Velocity [6]
LAA Tissue Doppler velocities were obtained by placing the spectral mode of PW Doppler sample volume on LAA lateral wall midway between the LAA tip and outlet (figure 3).  Mild (minimal echogenicity located in the LA appendage or sparely distributed in the main cavity of the left atrium; may be detectable only transiently during the cardiac cycle; imperceptible at operating gain settings for two dimensional echocardiographic analysis) 2+ Mild to moderate (more dense swirling pattern than grade 1+ but with similar distribution; detectable without increased gain settings) 3+ Moderate (dense swirling pattern in the LAA, generally associated with somewhat lesser intensity in the main cavity; may fluctuate in intensity but detectable constantly throughout the cardiac cycle) 4+ Severe (intense echo density and very slow swirling patterns in the LAA, usually with similar density in the main cavity) PTMC Procedure: PTMC was performed using a standard transseptal approach with an Accura balloon. Written informed consent was obtained from all subjects before enrollment in the study. The study protocol was approved by the institutional ethics committee.

Statistical Methods
The data was analyzed by using statistical soft ware SPSS Version 17. Results were presented as tables and charts. Continuous variables were presented as mean±SD and categorical variables as percentages. Non parametric continuous variables were tested with paired sample t-test. Spearman's correlation coefficient was used to assess the correlation between SEC grading and LA appendage function.
Probability less than 0.05 was considered as significant.
Microsoft excel 2013 was used to generate the graphs. Table 2 summarizes the baseline characteristics of the patient population.   Table 3 and Figure 5 shows comparison of left atrial appendage function in patients with and without SEC before PTMC.

Results & Observations
Among the cases, 21 subjects had no SEC and 49 subjects had SEC on TEE. LAAAC (%) and PW Doppler velocities [LAAEDE Velocity (cm/s), LAALDE Velocity (cm/s), LAAF Velocity (cm/s)] were significantly less in patients who had SEC than patients who do not had SEC (p<0.05).
LAA Tissue Doppler velocities [E LAA Velocity (cm/s), A LAA Velocity (cm/s), S LAA Velocity (cm/s)] were also less in patients who had SEC than patients without SEC but it was statistically not significant (p>0.05).   Table 4 shows correlation between SEC grading and LAA function among the cases before PTMC.
There was also negative correlation between SEC grading and LAA Tissue Doppler velocities (E LAA Velocity, A LAA Velocity, S LAA Velocity) but it was statistically not significant (p>0.05).

Discussion
In 1983, Sigel et al. found in their experimental study that SEC indicated red cell aggregation by demonstrating that SEC severity, as determined by the video densitometric method, correlated positively with hematocrit and fibrinogen concentration, and inversely with shear stress [8][9][10]. Black et al. confirmed the relationship between SEC and blood components in patients with atrial fibrillation (AF), and found that LA SEC appeared in relation to hematocrit, fibrinogen concentration and LA dimension, but not to platelet count [11]. In patients with MS, due to low flow velocity and low shear conditions, RBC aggregates form by noncovalent binding between red cells and plasma proteins. RBC aggregates thus formed lead to increased blood echogenicity causing ultrasonic backscatter and produce a pattern of smoke or SEC in LA. SEC is associated with clot formation and embolic phenomena.

Comparison of Baseline Left Atrial Appendage Function in Patients with and Without SEC Before PTMC
In the present study mean LAAAC% and LAA PW Doppler velocities were significantly less in patients with SEC when compared with patients without SEC implying more severe LAA dysfunction in patients with SEC. LAA Tissue Doppler velocities were also less in patients with SEC compared to patients without SEC but it was statistically not significant. Thus presence of SEC could be an indicator of severe LAA dysfunction among patients of severe rheumatic MS, who are at high risk of systemic thromboembolism.

Correlation of SEC Grading with Left Atrial Appendage Function Before PTMC Among the Cases
In the present study we correlated degree of SEC with LAA function among the cases, there was a significant negative correlation between SEC grading and LAAAC (%) and LAA PW Doppler velocities (LAAEDE Velocity, LAALDE Velocity and LAAF velocity), i.e. greater the intensity of SEC lesser was the LAAAC (%), LAAEDE Velocity, LAALDE Velocity and LAAF velocity, suggesting more severe LAA dysfunction among patients with greater degree of SEC. There was also negative correlation between SEC grading and LAA Tissue Doppler velocities (E LAA Velocity, A LAA Velocity, S LAA Velocity) but it was statistically not significant. Thus greater density of SEC indicates greater severity of LAA dysfunction and higher risk of thrombus formation among patients of severe rheumatic MS.

Effect of PTMC on SEC Grading
In the present study before PTMC out of 75 cases, SEC was present in 50 (66.66%) cases. Immediately post PTMC SEC completely disappeared in 19 cases and reduced in 31 cases. At 6months follow up SEC completely disappeared in 25 cases and reduced in another 25 cases, hence successful PTMC results in gradual improvement of SEC by improving LAA function and may reduce future risk of thromboembolism. This result was similar to previous studies [6,[12][13][14][15][16].

Conclusions
Among the patients of severe rheumatic MS, presence of SEC is an indirect evidence of severe LAA dysfunction, greater the intensity of SEC, greater would be the severity of LAA dysfunction and higher risk of systemic thromboembolism even in patients who are in sinus rhythm and successful PTMC results in gradual improvement of SEC, hence relief of MS by PTMC not only provide hemodynamic benefits with symptomatic improvement but also reduces the future risk of thromboembolism by decreasing SEC formation which is the harbinger of thrombus formation.

Source of Funding
The entire study was done using available resources at our institute and no external funds were sought/utilized.