Background
Previous studies have reported abnormal left ventricular (LV) contraction in patients with mitral stenosis (MS). The aim of this study was to explore the serial changes in LV mechanics in patients with severe MS undergoing balloon mitral valvuloplasty (BMV) to understand the reversibility and determinants of abnormal LV contractile function.
Methods
Fifty-seven patients with severe MS and 19 healthy controls underwent echocardiographic examinations, including two-dimensional speckle-tracking-based LV global longitudinal strain (GLS) and global circumferential strain measurements. In patients with MS, the same measurements were repeated 72 hours after BMV.
Results
In comparison with controls, patients with MS had faster heart rates and lower LV end-diastolic volumes and LV ejection fractions ( P = .008). The magnitudes of both GLS and global circumferential strain were reduced in patients with MS ( P < .001 for both), with 48 patients (84.2%) having GLS below the 25th percentile of controls. BMV resulted in significant improvements in GLS and global circumferential strain (−14.6 ± 3.3% vs −17.8 ± 3.5% and −20.0 ± 5.0% vs −22.5 ± 4.6%, respectively, P < .005 for both). On multivariate analysis, left atrial volume, mean transmitral gradient, and LV end-diastolic volume were independently correlated with baseline GLS, whereas increment in LV end-diastolic volume was the only determinant of increased GLS after BMV.
Conclusions
LV deformation is reduced in patients with severe MS and is related to the hemodynamic severity of MS. BMV results in rapid improvement of LV deformation, which is correlated with serial improvement in LV diastolic loading. These findings suggest that reduced LV diastolic filling rather than an irreversible myocardial structural abnormality contributes predominantly to reduced LV mechanical performance in patients with MS.
Rheumatic heart disease (RHD) is one of the most common forms of cardiac diseases worldwide, particularly in developing countries, where it remains the second most common cause of cardiovascular morbidity and mortality after atherosclerotic vascular disease. Even in developed nations, where RHD has been almost eradicated, recent reports have emphasized the disturbing possibility of a resurgence of this disease.
Although the exact pathogenesis of RHD remains controversial, it is primarily a disease of the endocardium, causing permanent damage to the cardiac valves. Mitral stenosis (MS) is the most common valve lesion seen in chronic RHD and usually manifests with exertional dyspnea and features of right heart failure resulting from pulmonary venous, and subsequently pulmonary arterial, hypertension. Unlike the other commonly encountered valve lesions (mitral regurgitation, aortic stenosis, and aortic regurgitation), MS does not produce any significant hemodynamic load on the left ventricle, and therefore, left ventricular (LV) systolic dysfunction is believed to be an exceedingly uncommon occurrence in patients with MS. However, a few studies have reported that LV systolic dysfunction may not be uncommon in patients with rheumatic MS and may indeed contribute to the development of symptoms in these patients. Several mechanisms have been postulated to explain LV systolic dysfunction in patients with MS, including chronically reduced preload, resulting in adverse LV remodeling, and the extension of inflammatory process from the mitral valve apparatus into the adjacent myocardium. However, our understanding of the pathogenesis and significance of LV systolic dysfunction in MS remains inadequate. Therefore, the aim of the present study was to assess the burden of LV systolic dysfunction in patients with isolated severe MS, its determinants, and its reversibility with therapeutic interventions such as percutaneous balloon mitral valvuloplasty (BMV). Two-dimensional speckle-tracking echocardiography (STE) was used to assess LV systolic function, as it permits more comprehensive evaluation of LV myocardial contractile function than conventional measures such as LV ejection fraction (LVEF).
Methods
Study Population
This was a prospective study conducted at a tertiary care hospital in Nagpur, India, from October 2011 to April 2012. The study population comprised 57 patients with isolated severe rheumatic MS undergoing BMV and 19 age-matched and sex-matched healthy volunteers from the community who acted as controls. Patients with coexistent significant mitral regurgitation or aortic valve disease (more than mild severity ), established coronary artery disease (on the basis of history, evidence of regional wall motion abnormalities on baseline echocardiography, or significant lesion on coronary angiography performed in patients >40 years of age) or any other significant structural heart disease, diabetes mellitus, or chronic obstructive airway disease were excluded. The presence of acute rheumatic activity was ruled out on the basis of clinical assessment and normal antistreptolysin O titer, erythrocyte sedimentation rate, and C-reactive protein.
Complete transthoracic echocardiographic examinations were performed in all patients with severe MS before and 72 hours after BMV and in the members of the control group. In addition, in patients with MS, invasive hemodynamic data were also recorded at the time of BMV. All our patients were on metoprolol and furosemide, and these therapies were continued unchanged until discharge. The ethics committee of the hospital in Nagpur, where all subjects were recruited and underwent BMV, approved the study. Written informed consent was obtained from all patients and controls before their enrollment in the study.
Transthoracic Echocardiography
The echocardiographic examination was performed using a commercially available ultrasound system (iE33; Philips Medical Systems, Andover, MA), with a 2.5-MHz to 4.0-MHz transducer. Scanning was performed by a single experienced operator, with the patient in the left lateral position.
Complete two-dimensional and Doppler assessment was performed per the recommendations of the American Society of Echocardiography. Basic measurements included LV wall thickness, LV internal dimensions, and the left atrial (LA) anterior-posterior dimension, measured from the parasternal long-axis view. LV end-diastolic volume (LVEDV) and LV end-systolic volume and LVEF were calculated from the apical four-chamber and two-chamber views using Simpson’s biplane method. LA volumes were measured using the biplane area-length method or from the planimetered area from the four-chamber view (in the event the two-chamber view was foreshortened), as stated in the American Society of Echocardiography’s recommendations for the use of echocardiography in clinical trials. All chamber volumes were indexed to body surface area, and only the indexed values were used for analysis. The conventional indices for assessment of the severity of MS, such as mitral valve area (MVA) by planimetry and pressure half-time and the maximum and mean mitral valve pressure gradients, were measured as recommended.
STE
STE was performed on standard two-dimensional grayscale images of the left ventricle, obtained from the apical two-chamber, three-chamber, and four-chamber views as well as the parasternal short-axis views at the basal and middle levels. The images were obtained during an end-expiratory breath-hold at a frame rate of 60 to 80 frames/sec. All images were transferred to a workstation for further offline analysis.
The offline analysis was performed using automated software (2D Cardiac Performance Analysis; TomTec Imaging Systems GmbH, Munich, Germany). For each view, the LV endocardial border was manually traced in the end-systolic frame. The software then automatically divided the entire circumference of the left ventricle into six equal segments and generated myocardial strain curves by frame-by-frame tracking of the natural acoustic markers throughout the cardiac cycle. Longitudinal strain was derived from the apical two-chamber, three-chamber, and four-chamber views, whereas circumferential strain was calculated from the two short-axis views ( Figure 1 ). For all strain parameters, peak systolic strain was measured for each of the myocardial segments and averaged to derive global values (global longitudinal strain [GLS] and global circumferential strain [GCS]), which were used for the analysis.
Observer Variability
For the purpose of this study, interobserver and intraobserver variability for myocardial strain measurements was assessed by repeating the measurements in 12 subjects. Intrareader and interreader coefficients of variation were estimated as the root mean squares of the coefficients of variation, and intrareader and interreader intraclass coefficients were calculated using the method of Fleiss.
Invasive Hemodynamic Assessment
In all patients undergoing BMV, invasive hemodynamic data were obtained using standard techniques before and immediately after BMV. Peak and mean LA pressure, peak and mean transmitral pressure gradients, and LV end-diastolic pressure were recorded for each patient.
Statistical Analysis
The statistical analyses were performed using MedCalc version 12.3.0.0 (MedCalc Software, Mariakerke, Belgium). All values are expressed as mean ± SD or as numbers. Having a sample size of 18 subjects in each group resulted in 80% power to detect differences between the two groups at a significance level of .05. The sample size in the MS group was increased further to characterize smaller serial changes before and after BMV. The baseline clinical and echocardiographic parameters in the patients and the controls were compared using χ 2 tests for categorical variables and two-tailed independent-samples t tests for continuous variables. The clinical and echocardiographic parameters before and after BMV in patients with MS were compared using two-tailed paired t tests. Correlations among different echocardiographic and invasive hemodynamic parameters were assessed using Pearson’s correlation coefficients. Multivariate linear regression analysis was performed to identify the independent determinants of impaired LVEF and strain parameters in patients with MS.
Results
Baseline clinical and conventional echocardiographic parameters are presented in Table 1 . The mean age of patients with MS was 28 ± 6.4 years, and 16 (28.1%) were male. Seven patients with MS were in atrial fibrillation at the time of baseline echocardiographic, whereas the remaining 50 were in normal sinus rhythm. The average heart rate of patients with MS was significantly higher than that of controls (81.3 ± 18.7 vs 71.2 ± 10.7 beats/min, P = .03), even after excluding those with atrial fibrillation (79.7 ± 18.1 beats/min, P = .065).
| Variable | Patients with MS ( n = 57) | Controls ( n = 19) | P |
|---|---|---|---|
| Clinical characteristics | |||
| Age (y) | 28.1 ± 6.4 | 33.8 ± 12.1 | .07 |
| Men | 16 (28.1%) | 5 (26.3%) | .88 |
| Body mass index (kg/m 2 ) | 23.5 ± 3.5 | 22.6 ± 1.72 | .31 |
| Atrial fibrillation | 7 (12.2%) | 0 | .25 |
| Heart rate (beats/min) | 81.3 ± 18.7 | 71.2 ± 10.7 | .03 |
| Conventional echocardiographic measurements | |||
| LA volume (mL/m 2 ) | 56.2 ± 18.6 | 23.2 ± 6.1 | <.001 |
| End-diastolic interventricular septal thickness (mm) | 7.1 ± 1.2 | 6.8 ± 1.4 | .43 |
| LVEDV (mL/m 2 ) | 39.0 ± 12.7 | 44.0 ± 8.0 | .06 |
| LVESV (mL/m 2 ) | 16.9 ± 6.0 | 17.7 ± 3.6 | .52 |
| LV stroke volume (mL/m 2 ) | 22.1 ± 7.7 | 26.3 ± 5.1 | .01 |
| LVEF (%) | 56.4 ± 7.0 | 59.8 ± 3.5 | .01 |
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