European Journal of Cardiovascular Medicine

Cardiovascular disease (CVD) throughout the world is considered as major factor reducing the quality of life (1). Global burden of cardiovascular disease estimated by world health organization is about 10% and is considered as primary cause of death (2, 3). Coronary artery disease is obstruction in coronary artery & stenosis (≥ 50%) occurs in one or more coronary vessels and its prevention and treatment includes removing of obstruction for treating angina and preventing MI (4). Atherosclerosis, one of the major risk factor for CVD propagates on exposure to risk factors related to CVDs (5). Chronic inflammation and plaques deposition within arteries leads to atherosclerosis and these plaques stimulates inflammations that results in disturbed blood flow contributing to atherosclerotic cardiovascular disease (6). Hypertension is also a risk factor for CVDs, and arterial hypertension increases risk for cardiovascular diseases linked with atherosclerosis (7). Another study reports that hypertension for long time promotes atherosclerotic plaques formation leads to increasing prevalence of myocardial infarction and mortality associated with MI (8).

Coronary computed tomography angiography (CCTA) is non-invasive technique to determine coronary atherosclerotic disease hence CAD (9).  Mollet et al (2005) in their study reported that the degree of calcification and total occlusion is best assessed by CT and it is more accurate predictor than invasive angiography (10).

T-cadherin is a protein which is a third receptor for high molecular weight adiponectin. According to Genome-wide association study (GWAS), circulatory T-cadherin effects glucose metabolism and is associated with CAD (11). In atherosclerosis T-cadherin level is elevated in human aorta, carotid artery, smooth muscle cells and endothelium (12). Altered T-cadherin level can effect insulin sensitivity, contractile activity of vascular smooth muscle cells, extra cellular matrix, activity of nitric oxide synthase in endothelium etc (13). Khan et al (2023) in their study demonstrated that patients having atherosclerosis have greater circulatory T-cadherin when compared with healthy individuals (14). Elevation in Circulatory T-cadherin in plasma during CVDs and complications involved in CVDs indicating it as marker for early screening of atherosclerosis and CAD (15). Present study is design to predict coronary artery disease and risk for MI, assess with CTA and circulatory T-cadherin.

In this study, Total 140 subjects (70 cases and 70 controls) were enrolled from Hospital, University Medical College, IIMS&R, Lucknow after approval from Institutional Ethical Committee (IEC) and followed all the ethical standards with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All the subjects were enrolled in the study after taking complete history and informed consent. Cases were included, those having age in between 30-70 years, Referred for CTA with complain of heaviness in chest & breathlessness. Patients with CKD, hyperthyroidism, auto-immune disorders & pregnant women were excluded from the study. Healthy subjects having age in between 30-70 years were included as controls.

CTA was done on 128 slice Multi-detector computed tomography (MDCT). Coronary segments were visualized and the analysis was done to interpret the degree of stenosis. Significant stenosis was defined if the visualized lumen diameter found to reduce more than 50% otherwise the segment was considered non-diagnostic. CCTA was analyzed to interpret single vessel, double vessel and triple vessel involvement in CAD.

Major anthropometric and clinical parameters as risk factors for CVD are also estimated. Obesity was estimated measuring the waist circumference (WC) in both male and female patients, WC ≥ 90 cm for men and ≥ 80 cm for women was considered as obese. (16). Hypertension was measured using sphygmomanometer, blood pressure (BP) ≥ 140 mmHg (systolic) and/or ≥ 90 mmHg (diastolic) was considered as hypertension (17).

Among the clinical parameters, fasting blood glucose (FBS) and lipid profile was estimated using commercially available kits on fully automatic biochemistry analyzer. FBS ≥ 126 mg/dl were considered as T2DM (18) and total cholesterol (TC) > 200 mg/dl, High density lipoprotein cholesterol (HDL-C) < 40 mg/dl and Triglyceride (TG) > 150 mg/dl were considered having dyslipidemia (19). Circulatory level of T-cadherin was estimated using Enzyme linked Immune sorbent assay (ELISA). On the basis of CT angiography patients were categorized into three categories, single vessel involvement, double vessels involvement and three vessels involvement. After this categorization, circulatory T-cadherin was estimated in all the three groups and value was recorded. Statistical analysis was done using IBM SPSS 20.0 (Armonk, NY, USA). Values are represented as mean ± SD. ANOVA – analysis of variance or unpaired t-test was used wherever required. p- Value< 0.05 was considered as statistically significant..

When the demographic characteristics were analyzed, this was found that 28(40%) females and 42(60%) males were enrolled as cases in the study. This was observed among the cases that 20(28.5%) were in between 30-40 years of age, 18(25.7%) in between 41-50 years, 25(35.7%) in between 51-60 years and 07(10%) were in between 61-70 years of age. Among enrolled cases, total of 25(35.7%) were obese, 38(54.2%) were T2DM, 32(45.7%) having hyperlipidemia and 40(57.1%) were hypertensive those are associated with risk factors for CAD. Clinical signs and symptoms of acute chest pain were seen in 52(74.2%), Heaviness in chest in 55(78.5%) and difficulty in breathing was seen in 30(42.8%) individuals those were advised for CT angiography shown in Table 1 given below.

Table 1: Demographic characteristics of cases.

Multidetector computed tomography (MDCT) findings of coronary artery among cases are given in Table 2. It was observed that 15(21.4%) having single vessels blockage, 20(28.5%) having two vessels blockage and 35(50.0%) individuals have three vessels blockage.

Table 2: Multidetector computed tomography (MDCT) findings of coronary artery among cases.

When Circulatory T-cadherin level in plasma was estimated, the mean of T-cadherin was observed significantly high in cases when compared to controls (p<0.01) shown in Table 3.

Table 3: Comparison of  circulatory T-cadherin among cases & controls.

** Statistical significant at 0.01 level (2-tailed), p<0.01

*Statistical significant at 0.05 level (2-tailed), p<0.05

Circulatory T-cadherin levels were also estimated in all the individuals having single vessel blockage, two vessel blockage and three vessels blockage. This was observed that, mean of T-cadherin in patients having three vessels blockage was highest (7.79±0.73), when compared to two vessels blockage (7.33±0.76) and single vessel blockage (7.15±0.56). This overall difference in means of all three types of patients was statistically significant (p=0.007, p<0.05) shown in Table 4 below.

Table 4: Comparison of Circulatory T-cadherin among cases on the basis of MDCT findings.

** Statistical significant at 0.01 level (2-tailed), p<0.01

*Statistical significant at 0.05 level (2-tailed), p<0.05

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.

This study concludes that the estimation of Circulatory T-cadherin and CTA evaluation can be used to predict the complications due to coronary obstruction. They can be used for the prognosis during the treatment of   CVDs and its complications. Increased level of T-cadherin can give early indication of involved cardiac pathology that can be evaluated with the help of CTA, hence both can be used in determination, treatment, prognosis and in reducing the mortality rate due to CAD.

Conflict of Interest – Authors have no conflict of interest.

Funding – None.

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