Patients who attended the outpatient clinic of the Rheumatology Department at Al-Zahraa University Hospital and were diagnosed with rheumatoid arthritis according to the 2010 ACR-EULAR criteria and had no evidence of cardiovascular disease were included in this cross-sectional prospective study .
From January to June 2018, the study comprised 65 patients with RA and 36 healthy control volunteers who were age and sex matched.
Informed consent was taken from all participants. The study protocol was authorised by a local ethical committee [Ethics Committee of Faculty of Medicine for Girls, Al-Azhar University, Nasr City, Cairo, Egypt, Registered at Central Administration of Research & Development; Egyptian Ministry of Health: Reg No. RHBIRB2018122001].
We obtained informed ethical consents from all patients to participate in this study, as well as its publication according to the recommendations of the above-mentioned committee.
Evidence of coronary artery disease (CAD) as detected by clinical history, ECG or echocardiographic wall motion abnormalities, valvular or congenital heart disease, diabetes mellitus, hypertension, advanced renal or hepatic diseases, and inadequate image quality all excluded patients from this study.
The disease activity score (DAS28) was computed by counting the number of swollen and tender joints as well as the erythrocyte sedimentation rate in 28 joints (ESR). 
Patients were classified in remission if their DAS28 was less than 2.6, and active disease was defined as DAS28 greater than 2.6. As a result, patients were separated into two groups: active RA patients (39 patients) and remission RA patients (39 patients) (26 patients).
All participants underwent a history and physical examination, with a focus on the duration of the disease and the drugs they were taking at the time. Total serum cholesterol, serum creatinine, C-reactive protein (CRP), ESR, rheumatoid factor (RF), neutrophil lymphocytic ratio (NLR), and platelet lymphocytic ratio (PLR) were all tested.
Ultrasound equipment GE- Vivid 7 system (GE- Ultrasound, Horten, Norway) with M3S (3.5MHz) matrix probe and echo Pac version 8.0 were used for echocardiography. The American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACCI) criteria for echo-Doppler for Cardiac Chamber were followed. Adults' Echocardiography Quantification (13)
Echo examination was performed in the left lateral decubitus. Averages of three consecutive cycles were used for all echo data. Images were recorded from parasternal and apical windows and the following parameters were obtained:
I- Conventional echo Doppler measurements including:
o Left ventricular dimensions and functions .
o Trans- mitral Doppler flow velocities including early (E) and late(A) diastolic velocities, E/A ratio.
o LA anteroposterior diameter measured from 2D parasternal long axis view targeted M-mode.
o LA superior-inferior and medio-lateral diameters measured from the apical 4 chamber view.
o LA volumes were estimated by area length method, averaged from apical 4 and 2 chamber views measurement.
- LA volume included:
• Maximal LA volume [Vmax] measured at the end of systole just before mitral valve opening at the end of the T wave on ECG.
• Minimal LA volume [Vmin] was measured at end diastole just at the closure of the mitral valve.
• Pre contractile LA volume ( LAV pre-A] measured at P-wave onset on ECG just before atrial contraction.
• LA volume index (LAVI) was calculated for each of the above volumes as LA volume divided by body surface area [14 ].
II- TDI measures
II- TDI (Total Daily Intensity)
We used two apical views for the TDI velocity and TDI derived strain measurements (4&2 chamber views). Three complete cardiac cycles during end expiration were recorded and archived in a cine-loop format for data collection. To achieve a frame rate of more than 80 frames per second, the image sector width was adjusted as tiny as possible. To avoid aliasing in the image, special attention was made to the colour Doppler velocity range setting.
The sample volume was placed at postroseptal and lateral sites in the apical 4-chamber view, inferior and anterior sites in the apical 2-chamber view, to measure peak systolic myocardial velocity (Sa), early diastolic myocardial velocity (Average Ea), and late diastolic myocardial velocity (Average Ea), and late diastolic myocardial velocity (Average Ea (Average Aa). E/Ea was estimated as the ratio of E velocity from pulsed-Doppler echo to Ea from TDI.
Because of its thin-walled nature, the TDI of the LA was tested by putting sample volume at the mid atrial segment of interest, usually approximately 2 mm for measuring velocity and preferably not more than 12 mm for strain.
With little gain and lower filter settings, the velocity range was tuned at 20 to 30 cm/s.
III- Left atrium 2D Speckle tracking echocardiography examination:
To allow for strong delineation of the endocardial border and frame-to-frame tracking, 2D-STE was done on grey scale images with good image quality. The frame rate was set to 60-80 frames per second. The QRS onset was employed as a reference point, and the left atrium was analysed using a commercially available LV strain software package. The non-foreshortened apical 4-chamber view yielded 2D speckle tracking analysis of LA global longitudinal strain (LA-GLS) and left atrial peak longitudinal strain (LA-PLS) . The region of interest was expanded to embrace the whole myocardium of the left atrium. If necessary, manual corrections were made to improve tracking outcomes.
Analysis of the LA strain curve was done to measure:
1. Peak atrial strain during ventricular systole (εS) measured just before mitral valve opening and it is considered as a surrogate of the reservoir function.
2. Late peak strain just before the active atrial contractile phase (εCT) begins, at the onset of the P wave on the electrocardiogram, as a surrogate of the contractile function.
3. Early diastolic peak strain (εE) as a surrogate of the conduit function. It is measured as the difference between the (εS) and (εCT) [Fig.1, Fig.2]
The information was gathered, reviewed, tallied, and statistically assessed. The mean and standard deviation were used to express quantitative data. The unpaired Student t-test was performed to determine whether there was a statistically significant difference between two samples' means. To find statistically significant relationships between qualitative variables, the X2–test was performed. When the P value was less than 0.05, the result was regarded significant, and when it was less than 0.01 it was called very significant.