DISCUSSSION
This is the first prospective study that systematically assessed the
frequency of LAAI (defined by peak LAA emptying velocity
<25cm/sec) 7,8 in patients of severe
isolated RMS (MVA≤1.5cm2) in sinus rhythm. In our study 73% patient had
inactive LAA of which 53% had very severe MS (MVA ≤ 1
cm2) and 20% had severe MS (MVA >1 but
≤1.5cm2). On multivariable regression analysis, mean
gradient across mitral valve, serum fibrinogen and lateral mitral
annulus systolic velocity were found to be independent predictors of
LAAI. MVA assessed by planimetry failed to achieve statistical
significance as an independent predictor of LAAI in our study.
Hoit et al 16 and Bilge et al 17have shown that elevation of LA pressure causes reduction in LAA
emptying velocity. The degree of obstruction to outflow across mitral
valve is a predictor of LA pressure. In spite of similar mitral valve
areas, patients have variable LA pressure due to variable resistance to
flow across the mitral valve apparatus determined by the degree of
pliability of the valves and sub-valvular obstruction. These aspects of
obstruction across mitral valve apparatus are better reflected by the
mean transmitral gradient across MV than the MVA determined by 2D.
Hence, in our study, mean transmitral gradient was found to be an
independent predictor of LAAI over MVA assessed by planimetry.
In our study, another independent predictor of LAAI was serum fibrinogen
level. In patients of MS, local stagnation of blood in left atrium and
its appendage leads to activation of coagulation system and reversible
intercellular bridging between RBC principally by
fibrinogen.18 This local alteration of the coagulation
system also leads to increased levels of fibrinogen in peripheral blood19 and accordingly in our study the serum fibrinogen
level was significantly higher in patients with LAAI. Fibrinogen by
increasing blood viscosity contributes to increase in LAA afterload and
impairment in its contractility. 20 In our study, we
found that serum fibrinogen of ≥300 mg/dl had a sensitivity of 71.0%
and PPV of 73.27% in predicting LAAI.
Mitral annulus has an important role for LA and left ventricular (LV)
function by moving throughout cardiac cycle along the LV long axis.21-23 The excursion of the mitral annulus is
responsible for approximately 20% of total LV filling and emptying in
healthy subjects. 16 It also contributes to LA filling
by creating a suction effect during systole and contributes to LA
emptying by decreasing LA blood volume during
diastole.16-18 In patients of MS LV, LA and LAA
function are impaired and the excursion of the mitral annulus is reduced
due to scaring and inflammatory processes. In our study, we found a
strong positive correlation between Sa-wave and LAA peak emptying
velocity. The cut off value of Sa-wave to predict LAAI in our study was
6.8 cm/sec which was lower then cut off value reported by Cayle et al7 of 13.5 cm/sec and higher than the cut off value of
5.5 cm/sec reported by Arava et al. 24 This is due to
the fact Cayle et al 7 had enrolled patients with MVA
≥1.5 cm2 whereas Arava et al 24 had
enrolled patients of critical MS with MVA <1
cm2. The mean Wilkins score in our study was 7.3±0.8
which is less compared to the mean Wilkins score of 7.9±0.9 by Arava et
al. 24 The degree of damage to the MV apparatus in our
study was lesser than patients recruited by Arava et al24 and more than patients studied by Cayle et
al.7 Accordingly, the cut-off value of Sa obtained in
our study was lower than that by Cayle et al. and higher than that of
Arava et al.
In our study, two echocardiographic parameters assessed by TTE- mean
transmitral pressure gradient and lateral mitral annulus systolic
velocity were found to be independent predictors of LAAI. As TEE is an
invasive procedure requiring skill and has limited availability,
determination of mean transmitral gradient and lateral annulus systolic
velocity can help to predict LAAI by a non-invasive modality like TTE.
To the best of our knowledge, this is the first study that has analysed
and reported about two echocardiographic variables along with one
haematological factor (Serum fibrinogen) that can predict the presence
of LAAI with combined positive predictive value of around 80%.
In our study, LAAI was the only variable found to be an independent
predictor of LA/LAA smoke and associated thrombus. Ninety percent
patients with LAAI had evidence of LA/LAA smoke which is a risk factor
for thromboembolism. It has already been shown by Serkan et al4 that in patients of severe MS, there is similar
degree of impairment of LAA contractility, irrespective of whether the
patients are in AF or sinus rhythm.
So we feel that just as the presence of AF in patients of MS is
considered an indication for initiating oral anticoagulant therapy
[OAC] 25, presence of LAAI in patients of severe
MS in sinus rhythm should also be considered as an indication for
initiating OAC. Therapy with OAC should be continued till LAA afterload
imposed by the high transmitral gradient can be significantly reduced by
mitral valvuloplasty which have been shown to improve LAA contractility.24, 26