Interatrial Septal Thickness as a Predictor of the Presence and Severity of Coronary Artery Disease

Parvathareddy Krishna Mala Konda Reddy; Monica Rachana Rayapu; Srinivas Ravi; Praveen Nagula; Naga Venkata Raghava Balla; Saitej Reddy Maale

doi:10.4103/jiae.jiae_28_22

ORIGINAL RESEARCH

Year : 2023 | Volume : 7 | Issue : 1 | Page : 1-7

Interatrial Septal Thickness as a Predictor of the Presence and Severity of Coronary Artery Disease

Parvathareddy Krishna Mala Konda Reddy, Monica Rachana Rayapu, Srinivas Ravi, Praveen Nagula, Naga Venkata Raghava Balla, Saitej Reddy Maale
Department of Cardiology, Osmania General Hospital, Hyderabad, Telangana, India

Date of Submission	19-May-2022
Date of Decision	25-Jun-2022
Date of Acceptance	05-Jul-2022
Date of Web Publication	04-Jan-2023

Correspondence Address:
Dr. Praveen Nagula
Department of Cardiology, Osmania General Hospital, Hyderabad - 500 012, Telangana
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_28_22

Abstract

Background: Coronary artery disease (CAD) is the most prevalent cardiovascular disease. Even though the definitive diagnosis of CAD is by invasive coronary angiography (CAG), various imaging modalities and their advances have led to the evolution of noninvasive parameters such as epicardial adipose tissue (EAT), which could help in prediction of CAD. However, despite having a good association with CAD, the quantification of EAT is unreliable. The adipose tissue of the atrial septum is considered a surrogate of EAT. We aimed to study the association of interatrial septal thickness (IST) measured by echocardiography with the severity of CAD. Methods: A total of 200 patients with a probable diagnosis of CAD undergoing echocardiography and CAG were studied. The IST was measured using two-dimensional transthoracic echocardiography. The presence or absence, the extent, and the severity of CAD were known by CAG. Relevant statistical analysis was done to look for the association of IST with CAD. Results: The mean age of the population was 51.97 ± 10.19 years and the mean IST was 8.02 ± 3.2 mm. Of the baseline characteristics, age, hypertension, and history of CAD were found to be significantly associated with IST. There was significant association of IST with the presence of any extent of CAD. On multivariate regression analysis, IST was found to be an independent predictor of the presence of CAD, having positive association. A positive correlation (r = 0.868) was found between IST and the severity of CAD. The receiver operating characteristic curve analysis showed that IST >5.7mm predicted the presence of any CAD with a sensitivity of 78.6% and a specificity of 100%. Conclusion: IST, a measure of the adipose tissue of atrial septum, was found to be an independent predictor of the presence and severity of CAD.

Keywords: coronary artery disease, interatrial septal thickness, transthoracic echocardiography, coronary angiography

How to cite this article:
Reddy PK, Rayapu MR, Ravi S, Nagula P, Balla NV, Maale SR. Interatrial Septal Thickness as a Predictor of the Presence and Severity of Coronary Artery Disease. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:1-7

How to cite this URL:
Reddy PK, Rayapu MR, Ravi S, Nagula P, Balla NV, Maale SR. Interatrial Septal Thickness as a Predictor of the Presence and Severity of Coronary Artery Disease. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 May 29];7:1-7. Available from: https://jiaecho.org/text.asp?2023/7/1/1/367040

Introduction

In India, there is a rising trend of coronary artery disease (CAD), and the epidemiological transition from communicable diseases to noncommunicable diseases has occurred over a short period.^{[1],[2],[3],[4],[5]} To tackle this global epidemic, early detection and effective management of CAD is of utmost importance.

The definitive diagnosis of established CAD is by coronary angiography (CAG), either invasive or noninvasive using computed tomography CAG (CTCA). There is a growing need to identify the noninvasive markers of atherosclerosis. One such well-studied parameter is epicardial adipose tissue (EAT). The literature shows good correlation between EAT and the severity of the atherosclerotic disease.^[6],[7],[8] It can be quantified accurately by cardiac computed tomography but carries the risk of radiation exposure. The diffuse distribution and lack of appropriate quantitative measures limit the assessment by echocardiography.^{[9],[10],[11]} There is thus need for a new surrogate marker for quantifying EAT, overcoming these limitations.

It has been shown that adipose tissue of the interatrial septum (IAS) is a surrogate for EAT. Studies suggest that the posterior part of atrial septum is formed by the infolding of the atrial roof, which has EAT.^{[12],[13],[14],[15],[16]} Data from pathological specimens suggest that adipose tissue of the atrial septum is in continuity with EAT,^[15],[17] and atherosclerotic disease is more common in those with excess fatty deposits in the atrial septum.^[18] There is also a possible correlation between atrial septal thickness and atrial arrhythmias, sudden death, and CAD.^{[19],[20],[21],[22]}

The interatrial septal thickness (IST), a reliable equivalent of EAT, can be easily measured by transthoracic echocardiography (TTE) which is noninvasive, simple, cost-effective, time efficient and is a part of routine cardiac evaluation. However, there are no studies directly assessing the association between IST and CAD. Hence we performed this study to evaluate the association between IST and CAD.

Methods

A prospective, observational study of 200 patients was conducted in the Department of Cardiology, Osmania General Hospital, Hyderabad, after obtaining approval from the institutional ethics committee. Patients with age >18 years, having a probable diagnosis of CAD and undergoing coronary angiogram were included. Patients with atrial septal defects, atrial fibrillation/atrial arrhythmias, atrial septal aneurysms, atrial myxomas, tumors involving the atrial septum, and thrombus attached to the atrial septum were excluded from the study.

Baseline demographic data were collected. A clinical examination was performed, and vitals were recorded. Routine laboratory investigations, electrocardiography, and two-dimensional echocardiography were done for all the patients.

Echocardiographic data

Two-dimensional TTE was performed by an observer blinded to the study using Phillips iE33 (Philips, Minnesota, USA) echocardiography machine. IAS was assessed in the subcostal coronal view. IST was measured perpendicularly, inferior to the fossa ovalis, at the end diastole [Figure 1]. The average measurement obtained from three cardiac cycles was taken for statistical analysis. The IST was classified as thick and thin using the median value as the cutoff.

Figure 1: Figure showing the measurement of interatrial septal thickness in the subcostal coronal view inferior to the fossa ovalis at end diastole

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Angiographic data

As per clinical indication, patients underwent invasive CAG within 48 h of echocardiographic assessment in SIEMENS ARTIS PURE Cath lab (Siemens Healthineers AG, Erlangen, Germany). The evaluation of coronary artery stenosis using multiple projection quantitative analyses was done with CMS system (CMS, MEDIS, Leiden, Netherlands). The presence of more than or equal to 50% stenosis in the coronary arteries was defined as CAD. The severity of CAD was assessed by the SYNTAX score.

Echocardiographic and angiographic assessments were done by two separate observers blinded to the other study findings.

Statistical analysis

Data were entered in a predesigned proforma in a Microsoft Excel spreadsheet as well in the printed format. All the entries were double-checked for any keyboard error. The data collected were systematically analyzed using statistical software named Statistical Package for the Social Sciences (SPSS version 17.0 for Windows 7, Inc., Chicago, IL, USA). Descriptive and inferential statistical analysis was carried out in the present study. Results on continuous variables were presented as mean ± standard deviation (minimum–maximum), while results on categorical variables were presented as percentage (%). A P value of <0.05 was considered as significant.

Chi-square test was used to find the significance of differences in the categorical variables between two or more groups. Student's t-test (two-tailed, independent) was used to find the significance of differences in the continuous variables between two groups (intergroup analysis).

Multivariate logistic regression analysis was performed using the presence of any CAD as the dependent variable and the IST, other parameters as the independent variables. The receiver operating characteristic (ROC) curve was plotted to obtain the cut-off value of IST to predict the presence of CAD. As the IST was not normally distributed, Mann–Whitney U-test was performed to assess the association of IST with the SYNTAX score. A Spearman's rank correlation analysis was performed to assess the correlation between IST and the severity of CAD.

Results

A total of 200 subjects with a probable diagnosis of CAD undergoing CAG were studied.

Demographic data

The clinical characteristics of the patients are summarized in [Table 1]. The mean age of the population was 51.97 ± 10.19 years. More than two-thirds of them were males (72%). Out of the 200, nearly half of them were smokers (47%), one-third had history of alcohol consumption (33.5%), and 17% were obese. Of the cardiovascular comorbidities, the most common comorbidity was hypertension (51%) followed by dyslipidemia (39%) and diabetes (37.5%). Chronic kidney disease was seen in 6%. Of the clinical atherosclerotic cardiovascular disease, cerebrovascular accident was seen in 5.5%, peripheral vascular disease in 4.5%, previous history of CAD in 14.5%, and a family history of CAD in 5.5%.

Table 1: Baseline profile, comorbidities, cardiovascular diseases, and clinical presentation of the study population

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Clinical presentation

Of the 200 patients with suspected CAD, the most common presentation was unstable angina seen in 30.5% followed by anterior wall myocardial infraction (MI) in 26% and inferior wall MI in 14%; the least common presentation was non-ST elevation MI seen in 2%.

Angiographic profile

On angiographic analysis of the study population, 8% had normal epicardial coronaries and insignificant CAD was seen in 5%. Regarding the extent of CAD, single vessel disease was seen in 37.5%, double vessel disease in 35%, and 14% had triple vessel disease (TVD). The extensive form of CAD i.e., left main coronary artery with TVD (LMCA + TVD) was seen in 0.5%. The mean SYNTAX score of the study population was 12.51 ± 9.67 (range: 1–38). The distribution of SYNTAX score in the study population is given in [Table 2].

Table 2: SYNTAX score distribution in the study population

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Interatrial septal thickness distribution in the study population

The mean IST was 8.02 ± 3.2 mm (range of 3–16 mm). The median thickness was 7.55 mm (interquartile range 5.2 mm-10.0 mm). IST was divided into thick and thin based on this median value. Thick septal group constituted IST ≥7.55 mm and thin septal group with IST <7.55 mm; examples of thin and thick atrial septum are shown in [Figure 2] and [Figure 3].

Figure 2: Subcostal two-dimensional echocardiographic image of a patient with thin interatrial septum. The septal thickness measured at end diastole was 5.6 mm

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Figure 3: Subcostal two-dimensional echocardiographic image of a patient with thick interatrial septum. The septal thickness measured at end diastole was 16 mm

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Association of interatrial septal thickness with various parameters

Demographic parameters, risk factors, and comorbidities of patients with thick septum group were compared with thin septum group. Out of the clinical characteristics, age, hypertension, and history of CAD were associated with increased IST [Table 3].

Table 3: Association of various parameters with interatrial septal thickness

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Association of interatrial septal thickness with the presence and severity of coronary artery disease

A significant association was found between increased IST and the presence of any CAD. Multivariate logistic regression analysis [Table 4] showed that IST was independently associated with the presence of CAD (P = 0.001) with an odds ratio of 3.866 (95% confidence interval =1.76–8.49). Furthermore, there was a highly significant association between SYNTAX score and IST with a P < 0.0001(Mann -Whitney U- test).

Table 4: Multivariate logistic regression analysis for obtaining the independent determinants of the presence of any coronary artery disease

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A Spearman's rank correlation coefficient value of 0.868 also suggested a very strong correlation between IST and SYNTAX score, with a P < 0.0001 [Figure 4].

Figure 4: Scatter plot showing the correlation between SYNTAX score and interatrial septal thickness of the total study population. IAS: Interatrial septum

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When an ROC curve was plotted to predict the presence of any CAD, IST value of 5.7 mm showed the best combination of sensitivity (78.6%) and specificity (100%), with an area under the curve (AUC) of 0.924 [Figure 5].

Figure 5: Receiver operating characteristic curve showing the cut off value of interatrial septal thickness to predict the presence of any coronary artery disease. AUC: Area under the curve, IAS: Interatrial septum

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Discussion

This study was done to evaluate the association of IST measured by TTE with angiographic severity of CAD as assessed by SYNTAX score. The mean IST was 8.02 ± 3.2 mm. Age, hypertension, and history of CAD were found to be significantly associated with IST. This study showed a significant association of IST with the presence of any CAD. This association persisted even in the multivariate regression analysis. When IST was correlated with the severity of CAD, a positive correlation between the two was found.

Adipose tissue is a normal constituent of IAS. Deposition of fat in the IAS is a part of the generalized process along with an increase in subepicardial adiposity.^[18] In a previous study, on examination of 50 hearts in random,^[18] it was found that the fat in IAS was in continuity with the epicardial fat. The fat could get deposited in any available space in the IAS; however, fossa ovalis and the entrance sites of major vessels into atria, like coronary sinus were spared.^[19]

Schwinger et al.^[23] provided a detailed description of the anatomy of the IAS through their study in 150 patients with known or suspected cardiovascular disease. The IST was high at the site of IAS attachment to the atrial free wall. There was a constant region of thickness anterior and posterior to the fossa ovalis. The thickness gradually decreased toward centrally located fossa ovalis. The septum primum overlying the fossa ovalis was markedly thinner than the septum surrounding it.^{[24],[25],[26],[27],[28]} The region of constant thickness measured 6 ± 2 mm on an average before the atrial systole. The IST values ranged from 2 to 20 mm.^[23] In our study, the mean IST was 8.02 ± 3.2 mm and the median IST was 7.55 mm. Other studies showed a wide range of IST and that the median thickness varied based on the range. This might be because the distribution of IST is not uniform in any population and varies based on the age and also the population studied.

Agmon et al.^[29] in a population-based study found that age and increased body surface area (BSA) were significantly associated with IST. IST increased by 12.6% per 10 years of age and increased by 7.0% per 0.1 m² increase in BSA. Numerous other studies have also demonstrated that increased epicardial fat accumulation occurs with advancing age.^[30],[31] This age-related increase in fat deposition is shared by IAS. Our study also demonstrated a positive association of advancing age with increased IST. A combination of advancing age and obesity can result in an enormous collection of fat, and if it reaches a reasonable size, it is termed lipomatous hypertrophy of the IAS (LHIS).^[32] Interatrial fat maximal dimension more than 2.0 cm constitutes LHIS.^[33] In our study, the maximum atrial septal thickness observed was 16 mm in a 66-year-old smoker and hypertensive with ischemic cardiomyopathy whose CAG revealed TVD with a SYNTAX score of 38.

In our study, none of the patients without CAD had thick septum. This suggests the significant association of increasing IST with the presence of any CAD. The association persisted in a multivariate logistic regression analysis, independent of other risk factors. Similar findings were found in a study by Chaowalit et al.,^[22] where atrial septal thickness showed a significant correlation with the presence of any CAD (P = 0.03). Multivariate analysis also showed a significant association of atrial septal thickness with the presence of CAD, independent of age, sex, and body mass index (P = 0.05).

The potential mechanisms that could be hypothesized for this association are: first, interatrial adipose tissue, considered as a surrogate for EAT, has a possible function as paracrine and endocrine organ. It can secrete numerous bioactive molecules such as adiponectin, resistin, and inflammatory cytokines and thus can play a role in atherogenesis. Second, interatrial adipose tissue is related to cardiovascular risk factors and thus can be associated with CAD.

Previous studies had not performed ROC curve analysis to determine an IST cutoff to predict CAD. In our study, IST of >5.7 mm was found to predict the presence of any CAD with a sensitivity of 78.6% and a specificity of 100%. The AUC was 0.924, indicating very good accuracy of the test.

In our study, association between IST and severity of CAD as measured by SYNTAX score was found to be highly significant with a P <0.0001. Chaowalit et al.^[22] in their study had found a borderline association of IST with the severity score of coronary atherosclerosis (P = 0.066). Chakraborty et al.^[34] in a similar study concluded that thick septum group had a significant greater number of severe CAD patients compared to the thin septum group (78% vs. 14%, P <0.001).

In our study, a scatter plot showed a significant correlation of IST with the severity of CAD assessed by SYNTAX score. Spearman's rank correlation coefficient was 0.868 with a P <0.0001, suggesting a very high significance. Similar findings were observed from the study by Chakraborty et al.^[34] They had used Gensini score and the vessel score to assess the severity of CAD. The study concluded that IAS thickness had a positive correlation with Gensini score (r = 0.58) and the vessel score (r = 0.51), with a P <0.001.

Thus, an echocardiographic assessment of the IST can be used as a reliable predictor of the presence and severity of CAD. In our study, TTE was the modality used to measure the thickness of IAS. Even though transesophageal echocardiography (TEE) is the preferred modality to assess the characteristics of atrial septum, it cannot be employed routinely in all patients with suspected CAD. In contrast, TTE is cheap, simple, relatively easier, a part of routine cardiological evaluation and widely available compared to the TEE.

The major strength of this study is the usage of invasive CAG not only to assess the presence but also the severity of CAD. The measurement of IST and the assessment of angiographic severity were done by separate observers blinded to the study to eliminate bias.

Limitations

Potential drawbacks can occur in the measurement of atrial septal thickness. They include variability in the shape of atrial septum, difficulty in obtaining adequate subcostal view in some individuals, and interobserver and intraobserver variability.

Conclusion

This study concludes that IST is significantly associated with the presence and severity of CAD emphasizing that the echocardiographic assessment of IST can be used as a noninvasive predictor of severe CAD. The addition of IST measurement to the routine echocardiographic assessment can give a clue regarding the presence and severity of CAD. However, the promising efficacy of this novel noninvasive modality needs further studies for confirmation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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