Original Investigation

Evaluation of Atrial Conduction Times and Epicardial Adipose Tissue Thickness in Patients with Ankylosing Spondylitis


  • Ahmet Öz
  • Hüdanur Coşkun
  • Tufan Çınar
  • Süleyman Çağan Efe
  • Nuran Öz
  • Burak Ayça
  • Turgut Karabağ
  • Ebru Aytekin

Received Date: 08.08.2020 Accepted Date: 16.09.2020 IMJ 2020;21(6):430-435


In this study, we aimed to evaluate whether atrial electromechanical delay (EMD) and epicardial adipose tissue (EAT) thickness differed between ankylosing spondylitis (AS) patients and healthy subjects.


This prospective, cross-sectional study included 43 consecutive AS patients followed up in the Physical Medicine and Rehabilitation Department of the University of Health Sciences Turkey, İstanbul Training and Research Hospital, between June 2019 and January 2020. The control group consisted of 42 age-and gender-matched healthy participants. The PA atrial EMD was accepted as the beginning of the P wave on the electrocardiograph and the begining of late diastolic wave (Am wave) on the tissue Doppler obtained by transthoracic echocardiography, and all EMD parameters, including lateral mitral annulus (lateral PA), septal mitral annulus (septal PA) and right ventricular tricuspid annulus (tricuspid PA), were calculated. The thickness of EAT was obtained from the thickest part of the right ventricular free wall at the end of diastole in the parasternal long axis window.


In AS patients, tissue Doppler measurements of PA lateral, PA septal and PA tricuspid were longer than the measurements in the control group. In addition, EAT thickness was significantly higher in AS patients than in the control group. There was a moderate correlation between interatrial EMD and C-reactive protein (r=0.445, p<0.001) and EAT thickness (r=0.451, p<0.001).


In this study, interatrial EMD and intraatrial EMD were significantly higher in AS patients. In addition, the thickness of EAD was significantly greater in patients with AS. These findings suggest a higher tendency toward coronary artery disease and atrial fibrillation in patients with AS.

Keywords: Ankylosing spondylitis, electromechanical delay, epicardial adipose tissue, atrial fibrillation


Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that mainly affects the sacroiliac joints and axial skeleton (1). Extra-articular involvement in AS includes cardiovascular involvement findings such as aortic valve regurgitation, aortic root pathologies, and transmission disorders (2). In addition to AS patients, increased cardiovascular morbidity and mortality have been reported compared to the general population. Although the reason for this increase is not known exactly, the idea that chronic inflammation and autoimmunity play a role comes to the fore (3).

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia that causes increased mortality. The various pathophysiological mechanisms that lead to AF include structural and electrical abnormalities, tissue remodeling, and inflammation (4). Previous studies have shown that prolonged atrial transmission time or electromechanical delay (EMD) may predispose to AF in chronic inflammatory diseases such as systemic sclerosis, psoriasis vulgaris (5,6). The gold standard in the evaluation of atrial transmission time is invasively applied electrophysiological studies. Another simple and non-interventional method can be obtained by measuring the time (PA) from the beginning of the P wave in electrocardiography (ECG) to the beginning of the Doppler A wave on transthoracic echocardiography (TTE) (7). Inter and intraatrial EMD can be evaluated using this method.

Epicardial adipose tissue (EAT) located between the myocardium and visceral pericardium is the actual visceral adipose tissue of the heart. EAT is a metabolically active tissue and a source of various local inflammatory mediators. Echocardiography can be used as the most appropriate low-cost and non-radiation imaging method to evaluate EAT. Many studies have shown an association between EAT and the development of atherosclerotic cardiovascular diseases, metabolic syndrome, and AF, including coronary artery disease (CAD) (8,9). In this study, we aimed to evaluate whether there was a difference in atrial EMD and EAT thickness between AS patients with a complex inflammatory structure and fully healthy people.


Data Collection

Fourty three consecutive patients with AS who were followed in the University of Health Sciences Turkey, İstanbul Training and Research Hospital, Clinic of Physical Medicine and Rehabilitation between June 2019 and January 2020 were included in this prospective, cross-sectional study. The control group of 42 healthy participants was matched with the patient group in terms of age and gender. All patients enrolled in the study met the modified New York criteria for AS. The exclusion criteria in the study are as follows; atherosclerotic cardiovascular disease, left ventricular (LV) systolic or diastolic (> grade II) dysfunction, moderate-to-severe heart valve disorder, diabetes mellitus, thyroid dysfunction, chronic lung disease, poor display quality, conduction abnormalities and/or the presence of branch block in ECG, electrolyte disorder, the use of antiaritmic and/or antipsychotic medication. Key clinical features such as age, gender and body mass index (BMI), duration of disease and drugs used in treatment for all patients were recorded. For each patient, pain conditions, movement restrictions and disease activity were assessed by using  Bath Ankylosing Spondylitis Disease Activity index, Bath Ankylosing Spondylitis Functional index and chest expansion (Table 1).

This forward-looking, cross-sectional study protocol has been approved by the University of Health Sciences Turkey, İstanbul Training and Research Hospital Ethics Committee (decision no: 1849, date: 24.05.2019). A written informed consent form was obtained from all patients. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Transthoracic Echocardiography Evaluation

TTE examinations were performed in all patients with echocardiography device using 5-1 MHz S5-1 ultrasound probe (EPIQ 7; Philips Medical Systems, Bothell, WA, USA) in accordance with the standards of the American Echocardiography Association. During the examination, D2 derivation ECG was recorded continuously and the average of 3 consecutive measurements was calculated.

Conventional Echocardiography Measurements

From the parasternal long axis view window, LV end-systolic diameter, end-diastolic diameter, interventricular septum, posterior wall thickness, left atrial anteroposterior diameter, aortic root and ascending aortic diameter were measured by M-mode echocardiography. LV ejection fraction was measured by the Simpson’s method. Left and right atrium mediolateral and apicobasal diameters as well as left and right atrium areas were measured from the apical-4 space window. In pulsed wave Doppler echocardiographic examination, the sample volume was placed at the tip of the mitral valve and the mitral early diastolic filling rate (E), late diastolic filling rate (A), E/A ratio and deceleration time were measured from the apical 4-chamber image. Systolic movement of the tricuspid valve annular plane towards the apex was measured by placing the M-mode cursor at the junction point of the tricuspid valve and the free wall of the right ventricle in the apical 4-chamber view.

Tissue Doppler Parameters

Tissue Doppler evaluation was performed with the same device, using a spectral pulse Doppler signal filter at a Nyquist limit of 15-20 cm/sec, with an optimal gain. The monitor flow rate was adjusted to 50-100 mm/s to optimize the image of myocardial velocities. A pulse Doppler volume sample from the apical 4 gap window was taken from the systolic volume (SV) lateral mitral ring, septal mitral ring, and right ventricular tricuspid ring, and peak systolic (Sm), peak early diastolic (Em), and peak late diastolic (Am) velocities were measured from these samples.

Electromechanical Delay Measurement

The time between the onset of the P wave on the superficial ECG and the onset of the tissue Doppler late diastolic wave (Am wave) was defined as PA atrial EMD (atrial conduction time), and all atrial EMDs were measured from lateral mitral annulus (lateral PA), septal mitral annulus (septal PA) and right tricuspid annulus (tricuspid PA) (Figure 1). The difference between the PA durations measured from the SV lateral mitral annulus (ML) and the right ventricular tricuspid annulus (TL) regions was defined as interatrial EMD, the difference between the PA durations measured from SV lateral mitral annulus and septal mitral annulus (MS) was defined as intra-left atrial EMD, the difference between the PA durations measured from septal mitral annulus and right ventricular tricuspid annulus was defined as intra-right atrial EMD.

Epicardial Adipose Tissue Thickness

EAT thickness was obtained from the thickest part at the end of the diastole from the right ventricular free wall in the parasternal long axis window (Figure 2).

Laboratory Analysis

Blood values of the patients including erythrocyte sedimentation rate, C-reactive protein (CRP) and lipid values were obtained after 8 hours of fasting. The hematology analyzer (Beckman Coulter LH 780, FL, USA) was used to obtain the results of the full blood samples, while the CRP was measured using a biochemical analyzer (Beckman Coulter AU 680).

Statistical Analysis

SPSS statistical software version 22.0 (IBM, Chicago, IL, USA) was used to analyze the data. Kolmogorov-Smirnov tests were used to test whether the data was normal distribution. Mean ± standard deviation was used to express quantitative variables, while categorical variables were expressed in numbers and percentages. When comparing two groups for numerical variables, independent t-tests were used if there was a normal distribution. If there was no normal distribution, Mann-Whitney U tests were used. Chi-square tests were used to evaluate differences in categorical variables. Spearman correlation analysis was used to show the relationships between continuous variables. The power analysis of the study was evaluated using the G*power 3.1 program. The power of the study was 0.956 and the effect size was 1.413. P<0.05 was found to be statistically significant.


Fourty three AS patients and age and gender matched 42 healthy control subjects were included in our study. Clinical characteristics and laboratory findings for AS patients and healthy people and various disease activity parameters of AS patients are given in Table 1. In terms of laboratory findings, CRP was significantly higher in AS patients (p<0.05). Other laboratory parameters were similar between groups.

Analysis of Conventional Echocardiographic and Tissue Doppler Parameters

There was no significant difference between many conventional echocardiographic parameters in which the diameter and functions of the right and left spaces were evaluated and tissue Doppler parameters (Table 2). However, diameters and volumes of the right and left atria were significantly higher and septal annulus systolic myocardial velocity (Sm) was significantly lower in AS patients.

Atrial Electromechanical Delay and Epicardial Adipose Tissue Thickness

Doppler tissue measurements showed that PA lateral, PA septal and PA tricuspid in AS patients were more elongated than the control group (p<0.05 for each). With all Doppler findings indicating EMD, EAT thickness was significantly higher in AS patients than in the control group (Table 3).

Correlation Between Electromechanical Delay, Epicardial Adipose Tissue, Echocardiographic Parameters and Working Variables

A significant moderate correlation was found between interatrial EMD and CRP (r=0.445, p<0.001) and EAT thickness (r=0.451, p<0.001). Atria dimensions and correlation results between BMI and interatrial EMD are given in Table 4.


In our study, atrial EMD and EAT thickness were evaluated in patients with AS, and three main findings were as follows: 1) Interatrial EMD and intraatrial EMD were significantly higher in AS patients; 2) EAT thickness was significantly greater in AS patients; 3) there was a significant correlation between interatrial EMD and CRP, atrial sizes and EAT.

Although AS primarily affects the axial skeleton, it is a systemic chronic inflammatory rheumatic disease affecting extra skeletal tissues such as ophthalmologic, cardiac and neurological. Cardiac complications occur especially after a long illness period (2,10). Cardiovascular complications seen in 5-10% of patients are aortic root diseases, diastolic dysfunction, intracardiac transmission disorders, myocardial fibrosis and more rarely arrhythmia. It is also recently reported a trend towards increased subclinical atherosclerosis in patients with AS without clinical evidence of cardiac involvement. Fibrosis in the atrial tissue that arises as a result of inflammation may also contribute to conduction abnormalities and impairment of atrial mechanical function in patients with AS (3,11). However, recent studies have shown that there is a relationship between chronic inflammation and the development of AF, and infiltration by inflammatory cells in the atrial tissue has been observed in AF patients (12). It has been reported that atrial conduction disorders due to electrophysiological and electromechanical abnormalities increase the risk of developing AF (4). In addition, it has been shown in recent studies that prolonged intraatrial and interatrial electromechanical conduction times increase the risk of AF (13,14). In this study, we observed that intraatrial and interatrial conduction times increased in AS patients. Although there is still no clear evidence, it has been suggested that AS patients may be at high risk for developing AF as a result of increased chronic inflammation and myocardial fibrosis.

EAT, located between myocardium and visceral pericardium, is a type of visceral adipose tissue. EAT secretes a wide variety of active biological molecules that regulate vascular smooth muscle contraction. Paracrine effects arise from its proximity to adventitia and extravascular bed (15). TTE provides non-invasive evaluation of EAT. EAT is thought to play an important role in CAD and AF pathogenesis (8,9). In a study conducted, it was shown that EAT is associated with hypertension, atherosclerosis and coronary heart disease (16). It has been shown by Yamashita et al. (17) that there is relationship between increased EAT thickness measured on computed tomography and especially left anterior descending and right coronary artery coronary plaque load. There are also studies explaining the relationship between EAT and the development and severity of AF. In the Framingham Heart Study, it was shown that higher pericardial fat volume was associated with approximately 40% higher AF rates, even after adjusting for risk factors such as age, myocardial infarction, heart failure, BMI, and gender associated with AF (18). Batal et al. (19) reported that increased EAT thickness is an important predictor of AF load independent of age, BMI, or left atrial area, and that patients with permanent AF have a significantly thicker EAT than patients with paroxysmal AF or without AF. Another study showed that EAT was associated with AF even after adding other risk factors, and that every 10 mL increase in EAT volume increased AF rates by 13% (20). In addition, the association of EAT with recurrence after AF catheter ablation has been demonstrated. It has been shown that in patients with increased EAT, recurrence is observed earlier after the ablation procedure and EAT independently predicts the presence, severity and recurrence of AF (21). All these evidences show that there is a close relationship between EAT and CAD and AF. In our study, we observed significantly increased EAT thickness in AS patients. Our study had the following limitations. First, the main limitation was that there were a limited number of cases included in the study and that it was done in a single center. Therefore, multi-center studies involving large number of subjects are needed to validate the results of our study. Second, methods such as cardiac magnetic resonance or computed tomography for atrial remodeling and EAT evaluation were not used in this study. Therefore, it may be necessary to evaluate EAT and atrial remodeling with these methods in AS patients. Third, since a limited number of patients were included in the study, independent variables could not be evaluated by multiple analyses. Finally, the mean follow-up period of AS cases included in the study was relatively short. Since this time is not sufficient to show the development of AF and CAD, longer studies are required.


In this study, it has been shown that there is a prolongation in atrial EMG, that predicts AF in AS patients and an increase in EAT thickness, which also causes the development of CAD and AF. In addition, a significant positive correlation was found between interatrial and intraatrial EMD and EAT. These results suggest that it may cause increased CAD and AF development in AS patients. Therefore, AS patients should be followed closely in terms of cardiac involvement.


Ethics Committee Approval: The study was approved by the İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine Ethics Committee (decision no: 51436, date: 07.02.2018).

Informed Consent: Patients were included after their informed consent was obtained.

Peer-review: Externally peer-reviewed.

Authorship Contributions: Surgical and Medical Practices - E.D., B.K., E.Y., D.K., U.R.; Concept - E.D., Z.Ö., B.K.A., B.Ko.; Design - E.D., Z.Ö., B.K., B.K.A., D.K., U.R.; Data Collection or Processing - E.D., E.Y., B.Ko., M.S.B.; Analysis or Interpretation - E.D., B.İ., B.Ko., U.R., M.S.B.; Literature Search - E.D., B.K., B.İ., B.K.A., E.Y., U.R.; Writing - E.D., Z.Ö., B.İ., D.K.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

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