European Journal of Cardiovascular Medicine

The health burden of valvular heart disorders (VHD) is still present. Aortic stenosis and mitral regurgitation are the most prevalent forms of VHD, with a prevalence of approximately 13.3 million in Europe. It is well recognized that VHD is linked to the development of heart failure, particularly moderate and severe heart failure, which was detected in 14% of patients suspected of having heart failure. Clinical symptoms and proof of heart function impairment serve as the foundation for managing VHD. [1]. In order to assess the valve and identify cardiac dysfunction, imaging testing is crucial. When assessing heart function in individuals with suspected valvular disease, echocardiography is a readily available diagnostic tool with exceptional diagnostic value. Additionally, measuring the left ventricular ejection fraction (LVEF) might be a crucial predictor of cardiac function and the necessity of an invasive management approach. However, even if the ejection fraction remains normal, there may already be a disturbance in myocardial function. Myocardial damage may be irreparable if the LVEF is already compromised [2]. Consequently, an assessment to identify early cardiac dysfunction prior to LVEF impairment may stop additional myocardial structural damage. Since global longitudinal strain (GLS) can be used to identify subclinical myocardial impairment, it is a better metric than LVEF. Additionally, GLS is useful in assessing moderate heart impairment and exhibits good feasibility. Strain, which is expressed as a percentage, is an indication that provides details about any change in a segment's length in relation to the baseline length measurement. There are three strains in cardiac tissue because it is a three-dimensional thing. Myocardial deformation is shown by the strain analysis, which also shows a correlation with stroke volume. Three shear stresses (longitudinal–radial, longitudinal–circumferential, and circumferential–radial) and three normal strains (longitudinal, circumferential, and radial) influence left ventricular deformation. When the mitral valve contracts, longitudinal strain—represented as negative strain—occurs from the base to the apex [3]. The relative thickness of the left ventricular (LV) wall is shown by radial strain, which is displayed as a positive strain value. Last but not least, circumferential strain, which is shown as a negative value, is the anticlockwise movement of cardiac tissue from base to apex. Thickness is defined by a positive strain value, while shortening is defined by a negative strain value. The strain measurement is affected by a number of variables, including loading, preload, and afterload changes. LV geometric alteration can result from variations in LV load in patients with VHD. Because there are fewer screening paradigms and diagnostic techniques available, subclinical cardiac dysfunction frequently goes undetected and occurs before heart failure and other cardiovascular illnesses.

Study design: Observational, Cross-Sectional Study

Place of Study: Cardiology Department of ABVIMS and Dr RML Hospital, New Delhi-110001

Period of Study: December 2022 to November 2023

Sample size: 40 in each group (total 80)

Inclusion criteria:

• Adults (>18 years)
• Rheumatic mitral stenosis with normal Left ventricular ejection fraction

Exclusion criteria:

• Patients with hypertension
• Diabetes mellitus
• Rhythms other than the normal sinus rhythm
• Moderate-to-severe stenosis or regurgitation of other valves more than moderate mitral regurgitation
• Pericardial diseases
• History of coronary artery disease or wall motion abnormalities
• History of cardiac surgeries and post balloon mitral vulvuloplasty

Statistical Analysis:

For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism (version 5). Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests, which compare the means of independent or unpaired samples, were used to assess differences between groups. Paired t-tests, which account for the correlation between paired observations, offer greater power than unpaired tests. Chi-square tests (χ² tests) were employed to evaluate hypotheses where the sampling distribution of the test statistic follows a chi-squared distribution under the null hypothesis; Pearson's chi-squared test is often referred to simply as the chi-squared test. For comparisons of unpaired proportions, either the chi-square test or Fisher’s exact test was used, depending on the context. To perform t-tests, the relevant formulae for test statistics, which either exactly follow or closely approximate a t-distribution under the null hypothesis, were applied, with specific degrees of freedom indicated for each test. P-values were determined from Student's t-distribution tables. A p-value ≤ 0.05 was considered statistically significant, leading to the rejection of the null hypothesis in favour of the alternative hypothesis.

Progressive mitral stenosis has an average age of 25.8 years, a median age of 24.5 years and a range of ages from 20 to 34 years. The age range for severe mitral stenosis is 20 to 36 years old, with a mean of 29.1 years, a median of 30.0 years. The Normal group encompasses ages ranging from 20 to 40 years, with a mean age of 26.6 years, a median age of 25.5 years. The mean BSA for people with progressive mitral stenosis is 1.58 square meters, with a range of 1.55 to 1.68 square meters. The BSA of individuals with Severe Mitral Stenosis ranges from 1.60 to 1.73 square meters, with a mean of 1.69. The BSA ranges from 1.58 to 1.90 square meters, with a mean of 1.71 and a median of 1.72 in the Normal group.

The GLS for Progressive Mitral Stenosis ranges from -0.168% to -0.151%, with a mean of -0.160% and a median of -0.160%. The GLS for the group with severe mitral stenosis is -0.152% on average, -0.150% on the median, and -0.158% to -0.140% on range. The GLS for the Normal group ranges from -0.208% to -0.180%, with a mean of -0.195% and a median of -0.198%.

The average strain rate in the Progressive Mitral Stenosis group is 1.05, with values ranging from 1.03 to 1.08, a median of 1.05, and a standard deviation (SD) of 0.01448. The strain rate ranges from 1.02 to 1.05 for the Severe Mitral Stenosis group, with a mean of 1.04, a median of 1.04, and an SD of 0.00832. The strain rate range from 1.10 to 1.50 is greater in the Normal group, with a mean of 1.26, a median of 1.25, an SD of 0.10300, and a broader range.

In the Progressive Mitral Stenosis group, the mean GCS is -0.204%, with a median of -0.204%, a standard deviation (SD) of 0.00142, and values ranging from -0.208% to -0.201%. For the Severe Mitral Stenosis group, the mean GCS is -0.198%, the median is -0.198%, the SD is 0.00651, and the range is from -0.208% to -0.189%. The Normal group shows a more negative mean GCS of -0.247%, with a median of -0.248%, an SD of 0.02154, and a range from -0.280% to -0.208%.

In the Progressive Mitral Stenosis group, the mean strain rate is 1.05, with a median of 1.05, a standard deviation (SD) of 0.01185, and values ranging from 1.03 to 1.07. The Severe Mitral Stenosis group has a mean strain rate of 1.06, a median of 1.06, an SD of 0.00891, and a range from 1.04 to 1.07. The Normal group exhibits a higher mean strain rate of 1.53, with a median of 1.50, an SD of 0.13280, and a wider range from 1.30 to 1.70.

In the Progressive Mitral Stenosis group, the mean EF is 57.8%, with a median of 58.0%, a standard deviation (SD) of 1.56, and values ranging from 55.0% to 60.0%. For the Severe Mitral Stenosis group, the mean EF is slightly lower at 56.6%, with a median of 57.0%, an SD of 1.13, and a range from 55.0% to 58.0%. The Normal group has a mean EF of 57.9%, a median of 58.0%, an SD of 1.85, and a range from 55.0% to 60.0%.

For the Progressive Mitral Stenosis group, the mean LVEDV is 83.4 mL/m², with a median of 84.0 mL/m², a standard deviation (SD) of 1.24, and values ranging from 80 to 88 mL/m². The Severe Mitral Stenosis group has a lower mean LVEDV of 79.3 mL/m², a median of 80.0 mL/m², an SD of 3.01, and a range from 74 to 84 mL/m². The Normal group shows a mean LVEDV identical to the Progressive Mitral Stenosis group at 83.4 mL/m², with a median of 83.0 mL/m², an SD of 2.01, and a range from 80 to 88 mL/m².

For the Progressive Mitral Stenosis group, the mean LVESV is 35.0 mL/m², with a median of 35.0 mL/m², a standard deviation (SD) of 1.880, and values ranging from 32 to 38 mL/m². The Severe Mitral Stenosis group has a slightly lower mean LVESV of 34.4 mL/m², a median of 34.0 mL/m², an SD of 0.770, and a range from 32 to 36 mL/m². The Normal group shows a mean LVESV of 35.0 mL/m², with a median of 35.0 mL/m², an SD of 1.709, and a range from 32 to 38 mL/m².

In the Progressive Mitral Stenosis group, the mean MVA is 1.77 cm², with a median of 1.70 cm², a standard deviation (SD) of 0.166, and values ranging from 1.60 to 2.20 cm². For the Severe Mitral Stenosis group, the mean MVA is significantly lower at 1.04 cm², with a median of 1.10 cm², an SD of 0.345, and a range from 0.40 to 1.50 cm². The Normal group shows a considerably higher mean MVA of 3.10 cm², with a median of 3.00 cm², an SD of 0.253, and values ranging from 2.60 to 3.60 cm².

The Comparison of Echo cardiographic factors in Valvular heart disease is show in in table 1.

Table -1 The Comparison of Echo cardiographic factors in Valvular heart disease

We derived the correlation between EF, GCS and GCS. Our results showed a moderate negative correlation between EF and both GLS and GCS. Specifically, the Pearson's correlation coefficient between EF and GLS is -0.347, indicating a negative linear relationship. This implies that as GLS decreases (becomes more negative), EF tends to decrease as well. The coefficient of determination, representing the proportion of variance in EF explained by GLS, is 12%, indicating that approximately 12% of the variability in EF can be explained by changes in GLS. The p-value of 0.028 suggests that this correlation is statistically significant. This as shown in Table 2.

Table 2: Correlation of Ejection fraction and GLS, GCS in Progressive mitral stenosis

The table presents correlation analysis results between Ejection Fraction (EF) and two myocardial strain parameters: Global Longitudinal Strain (GLS) and Global Circumferential Strain (GCS).

Similarly, the correlation between EF and GCS yields a Pearson's coefficient of -0.373, suggesting a slightly stronger negative correlation compared to GLS. The coefficient of determination is higher at 13.9%, indicating that GCS accounts for approximately 13.9% of the variability in EF. The low p-value of 0.018 further underscores the statistical significance of this correlation.

Our results also showed robust negative correlations, with the Pearson's correlation coefficient between EF and GLS at -0.759 and EF and GCS at -0.831. These coefficients indicate a substantial negative linear relationship, suggesting that as GLS and GCS decrease (become more negative), EF tends to decrease as well.The coefficients of determination further underscore the strength of these correlations, with GLS explaining 57.6% and GCS explaining 69.1% of the variability in EF, respectively. This implies that a significant proportion of the variability in EF can be accounted for by changes in GLS and GCS.

The low p-values (< .001) associated with both correlations indicate that these findings are statistically significant, reinforcing the robustness of the observed relationships between EF and myocardial strain parameters

The low p-values (< .001) associated with both correlations underscore their statistical significance, affirming the robustness of the observed relationships between EF and myocardial strain parameters.

Table 3: Comparison of Left ventricular strain with valvular disease

The coefficients of determination provided in the table 3. offer insight into the relationship between Ejection Fraction (EF) and two myocardial strain parameters, Global Longitudinal Strain (GLS) and Global Circumferential Strain (GCS), across different degrees of mitral stenosis severity. For individuals with Progressive Mitral Stenosis, GLS and GCS explain a modest proportion of the variability in EF, with coefficients of determination of 12% and 13.9%, respectively. However, as the severity of mitral stenosis progresses to the Severe stage, the explanatory power of both GLS and GCS substantially increases. In this group, GLS accounts for 57.6% and GCS for 69.1% of the variability in EF. Similarly, in the Normal group, where cardiac function is least impaired, GLS and GCS demonstrate significant explanatory capabilities, with coefficients of determination of 42.5% and 65.6%, respectively. These findings suggest that as mitral stenosis severity increases, the ability of GLS and GCS to predict EF changes becomes more pronounced, underscoring their potential utility as valuable indicators of cardiac function across varying stages of mitral stenosis.

The most common cause of mitral stenosis (MS) is still rheumatic heart disease. People with Severe Mitral Stenosis are typically older than those with Progressive Mitral Stenosis or normal cardiac function, according to an analysis of the mean ages of the three categories: Progressive Mitral Stenosis (25.8 years), Severe Mitral Stenosis (29.1 years), and Normal (26.6 years). Furthermore, the Normal group exhibits the highest level of age variability. The evaluation of left ventricular dysfunction in isolated mitral stenosis was the main emphasis of Elgendi et al. [4]. According to the BSA statistics, those with Progressive Mitral Stenosis (mean BSA of 1.58 square meters) have lower mean BSA values than people with Severe Mitral Stenosis (1.69 and 1.71 square meters, respectively). According to this research, BSA may be a helpful metric for assessing and identifying the degree of mitral stenosis.

According to the study, people with Progressive Mitral Stenosis (-0.160%) and Severe Mitral Stenosis (-0.152%) have larger negative mean GLSs than those in the Normal group (-0.195%). Since a greater negative GLS represents better systolic function, this suggests that the Normal group had better myocardial function. The findings demonstrated that, in comparison to the control group, patients with severe MS had lower absolute GLS values and LVEF values. Interestingly, GLS was below the 25th percentile of controls in 48 (84.2%) of the severe MS patients. GLS significantly improved after balloon mitral valvuloplasty (BMV) (pre-BMV: -14.6±3.3% vs. post-BMV: -17.8±3.5%).

In contrast to the Progressive (1.05) and Severe Mitral Stenosis (1.04) groups, the Normal group has a considerably higher mean GLSR (1.26), indicating superior myocardial function. A wider range of cardiac function is also shown by the Normal group's higher variability (SD = 0.10300). The mean GCSR (1.53) of the Normal group is substantially greater than that of the Progressive (1.05) and Severe Mitral Stenosis (1.06) groups. Additionally, GCSR variability is higher in the Normal group (SD = 0.13280) than in the Progressive (SD = 0.01185) and Severe Mitral Stenosis groups (SD = 0.00891). Elgendi and associates.[4] Noted that lower strain rates are suggestive of compromised myocardial function in patients with mitral stenosis, underscoring the significance of strain rate measures in identifying myocardial dysfunction. The mean EF for the group with progressive mitral stenosis was 57.8%, the median EF was 58.0%, the SD was 1.56, and the range was 55.0% to 60.0%. The mean EF in the group with severe mitral stenosis was 56.6%, the median EF was 57.0%, the standard deviation was 1.13, and the range was 55.0% to 58.0%. In the Normal Group, the range was 55.0% to 60.0%, the mean EF was 57.9%, the median EF was 58.0%, and the standard deviation was 1.85.

Both the Normal and Progressive Mitral Stenosis groups have mean EFs that are higher than those of the Severe Mitral Stenosis group, according to the data. Additionally, the Normal group exhibits the highest degree of EF variability. A lower EF is frequently a late indicator of myocardial damage, they said. According to Zhang et al.(7), the slightly lower EF in the group with severe mitral stenosis emphasizes the necessity of sophisticated imaging methods for early identification. The mean EF was highest in the Normal Group. The mean EF of the Severe MS Group was lower than that of the Normal group in this study. The Progressive MS Group, on the other hand, had the lowest mean EF, indicating the greatest degree of systolic function deterioration. The mean LVEDV for the group with progressive mitral stenosis was 83.4 mL/m², the median was 84.0 mL/m², the standard deviation was 1.24, and the range was 80 to 88 mL/m². The mean LVEDV for the group with severe mitral stenosis was 79.3 mL/m², the median was 80.0 mL/m², the standard deviation was 3.01, and the range was 74 to 84 mL/m². The Normal Group's LVEDV ranged from 80 to 88 mL/m², with a mean of 83.4 mL/m², median of 83.0 mL/m², and standard deviation of 2.01.

 Additionally, the group with severe mitral stenosis has the most variability in LVEDV. The impact of mitral stenosis on the volume and function of both ventricles was examined by Vijay et al. [5].This is consistent with the Severe Mitral Stenosis group's observed lower mean LVEDV (79.3 mL/m2) when compared to the Normal and Progressive Mitral Stenosis groups (both 83.4 mL/m²). The study highlights that because to limited ventricular filling, decreased LVEDV is frequently observed in severe instances. These results are corroborated by the Severe Mitral Stenosis group's reduced LVEDV when compared to the Progressive Mitral Stenosis and Normal groups, which shows how the severity of the stenosis affects ventricular volume. They contend that measuring LVEDV is essential for determining the degree of functional impairment. The focus on LVEDV as a sign of diastolic dysfunction in severe cases is in line with the reported decrease in LVEDV in the group with severe mitral stenosis. While concentrating on right ventricular function, Fennira et al. [6] also observed the dependency of ventricular volumes The LVESV range for the Progressive Mitral Stenosis group was 32 to 38 mL/m², with a mean of 35.0 mL/m², median of 35.0 mL/m², and SD of 1.880. The mean LVESV for the group with severe mitral stenosis was 34.4 mL/m², the median was 34.0 mL/m², the standard deviation was 0.770, and the range was 32 to 36 mL/m². The normal group's LVESV ranged from 32 to 38 mL/m², with a mean of 35.0 mL/m², median of 35.0 mL/m², and SD of 1.709.

Additionally, the group with progressive mitral stenosis shows the highest LVESV variability. Vijay et al. (5) describe how the gradual decrease in systolic function and increased afterload cause LVESV to tend to rise with the severity of mitral stenosis. This suggests a complex interaction between systolic function and disease severity, which is largely consistent with the slightly lower LVESV in the Severe Mitral Stenosis group compared to the Progressive Mitral Stenosis group. The predictive importance of LVESV was emphasized by Zhang et al. [7], who pointed out that depending on the stage and severity of the mitral stenosis, rises or decreases in LVESV can indicate unfavorable outcomes. Patients with mitral stenosis (MS) frequently have left ventricular (LV) dysfunction. Even while reduced ejection fraction (EF) is a common symptom of LV dysfunction, some MS patients may still have subclinical LV dysfunction. There is ongoing discussion over the fundamental processes of this impairment. The MVA of the Progressive Mitral Stenosis group ranges from 1.60 to 2.20 cm², with a mean of 1.77 cm², a median of 1.70 cm², and a standard deviation (SD) of 0.166. The mean MVA of 1.04 cm², median of 1.10 cm², SD of 0.345, and range of 0.40 to 1.50 cm² are significantly lower for the Severe Mitral Stenosis group. With a median of 3.00 cm², an SD of 0.253, and values ranging from 2.60 to 3.60 cm², the Normal group, predictably, had the highest mean MVA of 3.10 cm². With the Severe Mitral Stenosis group showing the lowest mean MVA and the most variation in valve area, these results highlight the gradual decline in MVA from normal people to those with severe stenosis.

Global longitudinal strain (GLS) in both ventricles was much lower in patients with severe MS than in healthy controls, according to research by Vijay et al. [5]. This is consistent with the findings of this study, which show that lower MVA is associated with lower heart function as determined by strain measures. Using right ventricular speckle tracking technique, Fennira et al. [6] discovered that MS patients had less right ventricular strain. This adds to the evidence on left ventricular dysfunction by indicating that both left and right ventricular function are negatively impacted by severe mitral stenosis, which is defined by a markedly decreased MVA. The prognostic significance of speckle tracking echocardiography in evaluating unfavorable outcomes in MS patients was emphasized by Zhang et al. [7]. Mehrab Pari et al.'s investigations [8]

The lowest quantities were displayed by the severe MS Group, indicating a serious hemodynamic impairment. Intermediate volumes were displayed by Progressive MS Group. The normal group's highest volumes showed that their hearts were functioning normally.

Because of the restricted filling caused by stenosis, LV volumes decline in patients with severe MS. The importance of valve area on ventricular dimensions was highlighted by Roushdy et al. [10], who discovered that MS patients' LV sizes were dramatically lowered and improved following balloon mitral valvuloplasty (BMV).

With the highest negative strain values, the Normal Group demonstrated superior myocardial function. In contrast to the Normal group, the Severe Mitral Stenosis (MS) group displayed lower negative strain values, suggesting impaired cardiac function. The group with progressive mitral stenosis had the lowest negative strain values, indicating the greatest impairment. These results are consistent with a number of research. The pattern seen in the results from this investigation was also supported by Elgendi et al. [4], who discovered lower absolute strain values in MS patients as compared to controls. This data is useful for determining their level of risk and demonstrating why early intervention is necessary.

The Normal Group's mean MVA was the highest. The mean MVA for the Progressive MS Group was lower. The most severe stenosis was indicated by the Severe MS Group, which had the lowest mean MVA. The progressive character of the disease is highlighted by the notable decrease in MVA from the Normal to Progressive to Severe MS groups.

Significant information on heart function can be gained from the relationships between Ejection Fraction (EF) and myocardial strain metrics, such as Global Circumferential Strain (GCS) and Global Longitudinal Strain (GLS), throughout various severity stages of Mitral Stenosis (MS). The results suggest that the association between EF and strain parameters is influenced by the severity of MS, with larger correlations observed in cases of more severe MS. These findings are consistent with other research in the literature, which advances our knowledge of the potential significance of myocardial strain measures as markers of heart function. When Vijay et al. [5] looked at strain parameters in patients with severe MS, they discovered that both the left and right ventricles had much lower GLS than controls, which suggests that there is significant myocardial dysfunction in these patients. This confirms that there is a stronger correlation between EF and GLS in severe MS than in less severe phases, indicating a greater level of cardiac damage. This supports the findings of this study that strain measures are more sensitive markers of myocardial damage in MS by indicating that strain parameters can identify subclinical LV dysfunction even when EF is maintained. The results of this investigation are consistent with those of Elgendi et al. [4], who observed lower absolute strain values in MS patients as compared to controls. These results corroborate the study's finding that the explanatory power of GLS and GCS on EF variability increases with MS severity.

We concluded that Speckle Tracking Echocardiography (STE) is an effective and sensitive method for detecting early alterations in left ventricular (LV) strain in adult patients with rheumatic mitral stenosis (MS). Our findings indicate that LV strain parameters, particularly global longitudinal strain (GLS), can detect subclinical changes in LV function that are often missed by conventional echocardiographic methods. This non-invasive technique provides valuable insights into the degree of myocardial dysfunction, allowing for early intervention and management of patients with rheumatic MS. Therefore, integrating STE in routine echocardiographic assessments could improve outcomes in this patient population by facilitating timely therapeutic measures. Further research is recommended to establish standardized guidelines for using STE in various stages of rheumatic MS.

We concluded that Speckle Tracking Echocardiography (STE) is an effective and sensitive method for detecting early alterations in left ventricular (LV) strain in adult patients with rheumatic mitral stenosis (MS). Our findings indicate that LV strain parameters, particularly global longitudinal strain (GLS), can detect subclinical changes in LV function that are often missed by conventional echocardiographic methods. This non-invasive technique provides valuable insights into the degree of myocardial dysfunction, allowing for early intervention and management of patients with rheumatic MS. Therefore, integrating STE in routine echocardiographic assessments could improve outcomes in this patient population by facilitating timely therapeutic measures. Further research is recommended to establish standardized guidelines for using STE in various stages of rheumatic MS.

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