Comprehensive echocardiographic and speckle tracking strain analysis in rheumatic mitral stenosis patients before and after transvenous mitral commissurotomy

Percutaneous Transvenous Mitral Commissurotomy (PTMC) is the first line treatment for rheumatic mitral stenosis (MS). We sought to evaluate (1) changes in 2-dimensional (2D) echocardiographic and strain values and (2) differences in these values for patients in atrial fibrillation (AF) and sinus rhythm (SR) pre, immediately and 6 months post PTMC. Retrospective study of 136 patients who underwent PTMC between 2011 and 2021. We analyzed their 2D echocardiogram, Global Longitudinal Strain (GLS), Left Atrial Reservoir Strain (LAr-S) and Right Ventricle Free Wall Strain (RVFW-S) pre, immediately and 6 months post PTMC. At 6 months, mitral valve area increases from 0.94 ± 0.23 cm2 to 1.50 ± 0.42 cm2. Ejection fraction (EF) did not change post PTMC (pre; 55.56 ± 6.62%, immediate; 56.68 ± 7.83%, 6 months; 56.28 ± 7.00%, p = 0.218). Even though EF is preserved, GLS is lower pre-procedure; − 11.52 ± 3.74% with significant improvement at 6 months; − 15.16 ± 4.28% (p < 0.001). Tricuspid annular plane systolic excursion (TAPSE) improved at 6 months from 1.95 ± 0.43 to 2.11 ± 0.49 (p = 0.004). RVFW-S increases at 6 months from − 17.37 ± 6.03% to − 19.75 ± 7.19% (p = 0.011). LAr-S improved from 11.23 ± 6.83% pre PTMC to 16.80 ± 8.82% at 6 months (p < 0.001) post PTMC. Pre-procedure patients with AF have lower strain values (More LV, RV and LA dysfunction) with statistically significant difference for LAr-S (p < 0.001), GLS (p < 0.001) and RVFW-S (p < 0.001) than patients in SR. Patients with severe rheumatic MS have subclinical left and right ventricle dysfunction despite preserved EF and relatively normal TAPSE with significant improvement seen at 6 months post PTMC. AF patients have lower baseline strain values than SR patients.


Introduction
Percutaneous Transvenous Mitral Commissurotomy (PTMC) is an established treatment for severe rheumatic mitral stenosis (MS) since its first publication in 1984 [1]. The aim is to crack the fused commissures thereby increasing the mitral valve area and reducing the mean pressure gradient (mean PG) across the mitral valve [2,3]. Prior studies have shown that the left ventricle (LV) ejection fraction (EF) is preserved in MS and the EF also does not change significantly immediately post PTMC [2][3][4]. Speckle tracking strain allows us to look at subclinical left ventricle (LV) and right ventricle (RV) dysfunction by analyzing Global Longitudinal Strain (GLS), Right Ventricle Free Wall Strain (RVFW-S) and left atrial dysfunction by looking at Left Atrial Reservoir Strain (LAr-S) [5][6][7][8]. With regards to subclinical LV and RV dysfunction, there are prior studies showing reduction in Global Longitudinal Strain (GLS) and Right Ventricle Free Wall Strain (RVFW-S), but the study population is small, and these studies only analyzed pre and immediate post PTMC values [7][8][9][10][11][12][13][14]. To our knowledge, this is the first study that tracks all aspects of strain (GLS, RVFW-S and LAr-S) pre, immediately and 6 months post procedure. Atrial fibrillation (AF) commonly coexists with MS and there is no study thus far looking at baseline strain values and response to PTMC in this group of patients compared to those in sinus rhythm (SR) [15,16].

Materials and methods
We looked at medical records of all patients who underwent PTMC at our center from 2011 to 2021.All patients included had mitral valve area < 1.5cm 2 . We excluded patients with more than mild mitral regurgitation and those whose echocardiographic images were deemed not suitable for strain analysis. This study has been approved by out institution ethics committee.

Echocardiographic data
All the patients' echocardiographic images were analyzed using the Synapse Cardiovascular software. We analyzed the images looking at 8 echocardiographic parameters. To evaluate the left heart, we measured biplane Simpson EF and left atrial volume index (LAVI), and to evaluate the mitral valve we measured mitral valve area by planimetry (MVA) in short axis view, and mitral valve area by pressure half time (MVA PHT) in apical 4 chamber view. In patients with atrial fibrillation (AF) we averaged 3 cardiac cycles to acquire measurements. For the right heart, we measured systolic pulmonary artery pressure (s-PAP), calculated from maximum tricuspid regurgitation velocity (TR Vmax) and inferior vena cava (IVC) size and collapsibility 5 mm distal to hepatic vein insertion, tricuspid annular plane systolic excursion (TAPSE) and right ventricle fractional area change (FAC).

Strain analysis
Only patients with suitable apical 4 chamber (A4C), apical 2 chamber (A2C) and apical 3 chamber (A3C) views were included in the study. The strain was analyzed retrospectively using Tom-Tec software. We analyze global longitudinal strain (GLS), right ventricle free wall strain (RVFW-S) and left atrial reservoir strain (LAr-S). Echocardiography and strain analysis was performed for all enrolled patients pre-PTMC (within one-month pre-procedure), immediately post-procedure (one day post-procedure) and 6 months after the procedure. This is the standard echocardiographic follow up protocol for PTMC patients in our setting (Fig. 1a, b and Fig. 2a, b).

Statistical analysis
Numerical measurements were expressed as mean ± standard deviation, whereas categorical data expressed as frequency and proportion. A repeated measures ANOVA was used to compare differences between groups at different times points with a Greehouse-Geisser correction and post hoc analysis of Bonferroni correction where applicable. P values < 0.05 were considered statistically significant. Statistical analysis was performed using SPSS ver. 27.0 (SPSS, Chicago, IL, USA).

Results
Overall, there were 136 patients with severe rheumatic MS who underwent PTMC during a 10-year period between 2011 to 2021 at our center. There were 113 (83.10%) female and 23 (16.90%) male patients. All these patients had no or mild MR. Overall age of intervention was 45.05 ± 13.34 years old (female; 45.42 ± 13.77 years old, male; 43.29 ± 11.03 years old). The mean Wilkins score was 6.60 ± 1.61. 82 (60.29%) patients had SR, and 54 (39.71%) patients had AF pre-PTMC. At the time of writing, all these patients are still alive with 16 (11.76%) of them underwent re-intervention. Pre-procedure, most patients are on loop diuretics (n = 78, 57.4%) and in New York Heart Association (NYHA) Class II (n = 73, 53.7%) (Table1). The average days between pre-intervention echocardiogram and intervention date is 27.6 ± 7.9 days, between intervention and immediate post echo is 1.8 ± 3.6 days and between immediate post echo to 6 months echo is 189 ± 22 days.

Discussion
The standard first line treatment for severe rheumatic MS is PTMC which has been done all over the world since the first publication of its' success in 1984 on 5 patients [1]. The aim of PTMC is to relief the obstruction across the mitral valve by cracking open the fused commissures, hence the name "commissurotomy" [1]. There are many studies showing significant increases in MVA and reduction in mean PG post PTMC [1][2][3]. PTMC is generally associated with good outcomes with low procedural and long-term mortality, but with significant need for re-intervention in the future. [17][18][19] In term of left ventricular function, there is a notion that MS protects the LV, thus systolic function should be preserved [13]. Many studies have shown that the EF is indeed preserved pre and immediately post PTMC [2][3][4]. Our study further confirms this fact and additionally demonstrates this phenomenon even at 6 months. Strain is a relatively new method to evaluate LV, RV and LA dysfunction before these become apparent using traditional 2D-echocardiographic parameters [20]. Strain analyzes the motion of tissues in the heart by using the naturally occurring speckle in myocardium and it values are expressed as percentage [20,21]. For GLS, the normal value is more negative than -18%, for RVFW-S normal value is more negative than -25% and for LAr-S normal value is more than 45% [22,23]. Utilization of speckle tracking strain in previous studies also demonstrated significant reduction in GLS amongst severe MS patients with preserved EF [6][7][8][9], with one study demonstrating a relationship between MS progression and GLS [14]. Our study is unique because we track the changes in GLS pre, immediately and 6 months post PTMC and found that while GLS did not improve immediately, there was significant improvement 6 months post PTMC with overall improvement of 31.6%. There are possibly three reasons for this subclinical LV dysfunction namely (1) restriction or tethering of posterobasal myocardium by the scarred mitral apparatus (2) abnormal interventricular septal motion related to RV overload and unequal filling of the two ventricles and (3) Limited LV distensibility and variable diastolic suction. After PTMC, as the LV filling improved, the preload increases and improves contractility. Reduction in RV pressure overload normalized the interventricular septum motion and further improves LV function [24].
As a result of the hemodynamic sequelae and back pressure from the obstructed mitral valve, patients with severe rheumatic MS commonly have increase in s-PAP [2,3]. Despite this, many studies have shown that the TAPSE is still above the cut-off for abnormal values based on the American Society of Echocardiography guidelines (Abnormal TAPSE < 1.7) [22,23]. In our study the TAPSE pre-PTMC is 1.9 ± 0.4 with no improvement immediately but significantly improve at 6 months ( Table 2). With regards to strain, prior to our publication there is a study that showed improvement in RVFS-S immediately post PTMC [8]. Like that study, we also found that RVFW-S was significantly depressed pre-PTMC, and as with GLS and TAPSE there were no immediate improvements, but RVFW-S improved significantly at 6 months post-PTMC.
Patients with severe MS all have left atrial dilatation, and many are at risk of developing atrial fibrillation [15]. In our study the LAr-S was markedly depressed but unlike GLS and RVFW-S, LAr-S improved immediately and continued to improve at 6 months post procedure. The 6 months period required for significant improvement in GLS, and RVFW-S seems to suggest that post PTMC, there is progressive positive remodelling of LV, RV, and left atrium.
This study also shows the importance of early intervention before AF develops. All strain parameters are lower for AF patients compared to those in sinus rhythm. Regardless of the rhythm at intervention, both groups of patients had significant improvement in their strain values post PTMC. Finally, there are 16 patients that required re-intervention (4 re-do PTMC and 12 mitral valves replacement). We are unable to find any statistically different strain parameters, except that those who required re-intervention had significantly lower EF.

Conclusions
Severe Rheumatic MS patients have significant impairment in left ventricle, right ventricle and left atrial function as illustrated by low GLS, RVFW-S and LAr-S. PTMC results in significant improvements in all strain parameters at 6 months post procedure. Patients with AF have significantly reduced strain parameters compared to patients in SR, however they still derive significant improvement from PTMC.