Assessment of immediate effects of percutaneous balloon mitral valvuloplasty on right ventricular and pulmonary functions in severe rheumatic mitral stenosis patients using speckle tracking echocardiography and spirometry

Introduction: The current study was sought to assess the immediate effect of percutaneous balloonmitral valvuloplasty (PBMV) on right ventricular (RV) and pulmonary functions using speckle tracking echocardiography (STE) and spirometry respectively. Methods: Two-dimensional speckle tracking and doppler studies for strain and strain rate imaging of RV were performed before PBMV, after 48h and 15 days of PBMV using echocardiography and spirometry. Mitral valve area, peak and mean mitral valve transannular pressure gradients, late filling velocities,Wilkins score, Systolic pulmonary artery pressure, TAPSE, RV end-diastolic and end-systolic areas,RV fractional area change and Tei index were measured. Results: There was a significant rise in peak RV global longitudinal strain (GLS) from baseline to48h post PBMV and at 15 days post PBMV. Segmental RV strain at basal septum, mid septum,apical septum and basal RV free wall showed considerable improvement from baseline to 48h post PBMV and 15 days post PBMV. RV longitudinal strain rate parameters did not show significant improvement after PBMV and remained low at follow-up. Post PBMV all patients showed restrictive features on pulmonary function test. The mean FEV1 (% predicted), mean FVC (% predicted), mean PEFR improved from baseline to 48h PBMV and 15 days post PBMV. Though the mean FEV1/FVC increased post PBMV at 15 days follow-up, but it was statistically insignificant. Conclusion: RV performance in MS was decreased mainly due to increase in RV after load which improves after PBMV. Patients with severe MS have impaired pulmonary function which is of restrictive type and successful PBMV improves pulmonary function.


Introduction
Rheumatic heart disease (RHD) is one of the noticeable causes of mortality and morbidity in developing countries across the globe. It has been estimated that 15.6 million people are affected by RHD globally. 1 Every year, approximately 470 000 new cases and 233 000 deaths were attributed due to RHD. 2 RHD is a major cardiac problem in India. The prevalence rates have been found to be 0.2 to 1.1/1000 populations. 3 Rheumatic mitral stenosis (MS) is the most common RHD which includes characteristic changes of the mitral valve include thickening at the leaflet edges, fusion of the commissures, chordal shortening and fusion. 4 Subsequent scarring leads to valve deformity resulting in a small fish mouth orifice. 5 Long standing pulmonary arterial hypertension can result in morphological changes in the pulmonary vasculature comprising of endothelial proliferation and medial hypertrophy. This causes secondary right ventricular (RV) overload, dilatation and failure.
Pulmonary dysfunction in severe MS is attributed to interstitial and alveolar edema, reactive fibrosis, pleural effusion and decreased lung volumes. 6 Abnormalities in RV function play vital role in the development of clinical symptoms and prognosis of MS patients. 7 Among many indices, strain and strain rate are novel to assess RV function. For the evaluation of RV function by strain and strain rate, Tissue Doppler imaging (TDI) is used. 8 A new method, Two-dimensional speckle tracking, to quantify strain and strain rate for assessment of global and regional myocardial function. Lack of angle dependency is the main advantage of strain derived by speckle tracking over strain derived by TDI, which may result in more reliable strain measurements.
There are studies on long-term improvement in RV and pulmonary functions in patients with MS after percutaneous balloon mitral valvuloplasty (PBMV) 9 whereas only few studies examined the immediate effect of PBMV on RV function using speckle tracking echocardiography (STE). 10 The current study was sought to assess the immediate effect of PBMV on RV and pulmonary functions using STE and spirometry respectively.

Data Collection
Baseline clinical and demographic characteristics were obtained from all patients. Two-dimensional speckle tracking and doppler studies for strain and strain rate imaging of RV were performed before and 48h after PBMV using American Society of Echocardiography recommendations 11 and spirometry using American Thoracic Society recommendations. 12 Echocardiography was performed by using SIEMENS ACUSON S2000 echocardiography machine with 3.5MHz probe. Spirometry was performed by using Easy One Pro TM Lab, ndd Medical Technologies Andover, MA, USA.
Mitral valve area (MVA) was determined by planimetry. The peak and mean mitral valve transannular pressure gradients and late filling velocities were measured using continuous wave doppler recordings through mitral inflow. Wilkins score 13 was used to judge mitral leaflet mobility, valvular and subvalvular thickening, and calcification. Systolic pulmonary artery pressure was derived from the tricuspid regurgitant jet peak velocity using the modified Bernoulli equation. The tricuspid annular plane systolic excursion (TAPSE) was determined by the difference in the displacement of the RV base during systole and diastole. RV end diastolic and endsystolic areas were measured from the apical four chamber view to calculate RV fractional area change (RVFAC). The Tei index of RV myocardial performance was calculated as the time between tricuspid valve closure to tricuspid valve opening, divided by the RV ejection time, determined by pulsed Doppler.
Two-dimensional images were acquired from the four-chamber view for offline analysis using the twodimensional strain software. The endocardial borders of the RV were traced manually by point and click approach and tracked by the software. An epicardial surface tracing is then automatically generated by the system. After manual adjustment of the region of interest, software automatically divides the region of interest into 6 segments. The RV free wall and interventricular septum were divided in three segments, basal, mid, and apical, for quantification of regional systolic strain. The GLS was calculated for the entire the right ventricle. 14 Spirometry was performed to evaluate the lung function disturbances, according to the recommendations of American Thoracic Society. 12 Patients were instructed to inhale as much as possible and then exhale rapidly and forcefully for as long as flow is maintained. Patient should exhale for at least six seconds. At the end of the forced exhalation, the patient should again inhale fully as rapidly as possible. The following parameters were determined --Forced vital capacity (FVC), forced expiratory volume in first second (FEV 1 ), FEV 1 /FVC and peak expiratory flow rate (PEFR) rate. Interpretation of pulmonary function tests: Restriction was defined as FVC< 80% of predicted with normal or increased FEV 1 /FVC. 15 Obstruction was defined low FEV 1 /FVC ratio (<0.7) and FEV 1 <80% predicted. 16 Mixed restriction and obstruction is defined as low FVC (<80% predicted), FEV 1 (<80% predicted) along with reduced FEV 1 /FVC ratio (<0.7). 16 Echocardiography was repeated 48 h after the procedure to evaluate the final MVA and to assess the degree of residual MR. Successful PBMV was defined as post valvuloplasty MVA >1.5 cm 2 with no more than 2+ MR. Two-dimensional (2D) speckle tracking, Doppler studies were repeated after 2 weeks to assess immediate changes in parameters. Pulmonary function tests were repeated after 2 weeks to assess immediate changes.

Statistical analysis
Continuous variables were expressed as mean and standard deviation (SD). Paired Student's t-test was used to determine the significance among the parameters pre and post PBMV. Statistical Package for Social Sciences (SPSS) version 20.0 (IBM Corp, Somers, NY, USA) was used for the analysis. A P value of ≤0.05 was considered as significant.

Results
This study findings were conceived from 52 symptomatic severe rheumatic MS patients who underwent PBMV. Mean age of the study population was 35.8±9.2 years. Majority of them were female patients (72%). Dyspnea was the presenting symptom in all the cases. Sixty one percent were in NYHA class-III and 39% were in NYHA class-II. Six patients (11%) had undergone prior PBMV and 2 patients (4%) had undergone prior closed mitral valvotomy (CMV). The mean Wilkins score was 6.5±1.2. Demographic and clinical characteristics of the study population at baseline were shown in Table 1.

Conventional echocardiographic parameters
Comparison of baseline and follow-up echocardiographic characteristics were summarized in Table 2. PBMV was generated a significant increase in mean MVA, TAPSE, FAC and a significant decrease in peak mitral valve gradient, mean mitral valve gradient, pulmonary artery systolic pressure (PASP) from baseline to 48 hours post PBMV and 15 days post PBMV. There was an insignificant increase in RV MPI at 48 hours post PBMV with lack of considerable improvement at 15 days post PBMV.

Speckle tracking echocardiographic parameters
Comparison of baseline and follow-up RV longitudinal strain parameters were shown in Table 3, Figure 1, Figure  2 and Figure 3. There was a significant rise in peak RV GLS from baseline to 48 hours post PBMV and at 15 days post PBMV follow-up. Segmental RV strain at basal, mid and apical septum and basal RV free wall showed considerable improvement from baseline to 48 hours post PBMV and 15 days post PBMV. No significant improvement was observed in segmental RV strain at mid RV free wall, apical free wall strain at 48 hours post PBMV and 15 days post PBMV.
In our study RV longitudinal strain rate parameters did not show significant improvement after PBMV and remained low at follow-up. Details of RV longitudinal strain rate parameters at baseline, post PBMV 48 hours and post PBMV 15 days follow up were summarized in Table 4.

Pulmonary function parameters
In our study 4 patients (7%) had obstructive airway disease and remaining of the 48 patients (93%) had restrictive    (Table 5).

Discussion
In our study there was a significant increase in 2D MVA, FAC, TAPSE at 48 hours following PBMV which was maintained post PBMV at 15 days follow-up. We observed a significant decrease in PASP, mean mitral valve gradient and peak mitral valve gradient. Similar findings were observed in studies done by Roushdy et al 17  Conventionally, for evaluation of procedural success, these echocardiographic parameters are valuable. In our study RV MPI showed no significant change after PBMV at 48 hours and at 15 days follow-up which shows that immediate improvement of RV function is due to decreased after load of RV. RV MPI is a load independent parameter of RV function. Similar observations were reported by Mohan et al. 7 In our study there was significant rise in RV GLS at 48 hours after PBMV and at 15 days follow-up. Also found a significant rise in RV segmental strain at basal septum of IVS, mid septum of IVS, apical septum of IVS, basal RV free wall at 48 hours post PBMV and at 15 days followup. Statistically insignificant difference was observed in RV segmental strain at mid RV free wall and apical RV free wall at 48 hours post PBMV and lack of improvement at 15 days follow-up. Similar findings were reported by Kumar V et al 19 and Alabaady M et al 18 . Enhanced LV filling and LV contractility following PBMV may be the reasons for improvement of IVS strain than RV free wall strain in our study.
We observed no change in RV segmental strain rates in any of the RV segments. Similar findings were reported by Roushdy et al and Kumar V et al. 17,19 Strain rate is more    20,21 The restrictive features may be due to chronic lung congestion due to increased interstitial fluid, decreased lung compliance and fibrosis from chronic congestion and consequent muscle fatigue.
In our study, 15 days post PBMV, there was significant improvement in pulmonary function parameters FEV 1 (%predicted), FVC (%predicted) and PEFR. However, the changes in FEV1/FVC were statistically insignificant. Similar observations were reported by Khan et al and Mundhra SH et al. 21,22 All the patients showed improvement of their ventilatory function after PBMV that may be due to reduction in left atrial hypertension, pulmonary venous congestion, resulting in increased lung compliance.
The number of patients studied were relatively less and study was done in severe MS patients only. Short axis images of RV were not recorded. Doppler strain was not included for comparison. Short duration of follow-up.

Conclusion
Right ventricular function can be assessed by global and segmental RV strain using STE comparable with conventional echocardiographic parameters. RV performance in MS is reduced mainly due to rise in RV afterload which improves after PBMV. Patients with severe MS have impaired pulmonary function which is of restrictive type and successful PBMV improves pulmonary function.

Competing interests
None.

Ethical approval
This study was conducted with a prior approval from the institutional ethics committee (IEC number: 639) and an informed consent was obtained from all the study participants prior to the enrolment.

Funding
None.