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