Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06593990
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-10
Brief Title:
LA Function and Dimensions As Predictors of Disease Activity in RA
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Left Atrial Function and Dimensions As Predictors of Disease Activity in Rheumatoid Arthritis Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
the aim of this study is to
describe subclinical echocardiographic changes of the LA dimensions and function in patients with rheumatoid arthritis
evaluate the correlation between Rheumatoid arthritis activity and subclinical structural changes of LA
determine the association of LA volume index and atrial fibrillation or HFpf in RA patients
apply Musculoskeletal Ultrasound detected synovitis to be correlated with cardiac function
describe subclinical echocardiographic changes of the LA dimensions and function in patients with rheumatoid arthritis
evaluate the correlation between Rheumatoid arthritis activity and subclinical structural changes of LA
determine the association of LA volume index and atrial fibrillation or HFpf in RA patients
apply Musculoskeletal Ultrasound detected synovitis to be correlated with cardiac function
Detailed Description:
Rheumatoid arthritis RA is a chronic progressive disease associated with systemic inflammation that affects mainly synovial joints leading to tissue destruction disability and excess mortality 1 With a prevalence ranging from 04 to 13 of the population depending on both sex women are affected two to three times more often than men age frequency of new RA diagnoses peaks in the sixth decade of life 2 RA has extra-articular manifestations that can impact multiple organ systems 3
RA patients remain at higher cardiovascular risk compared to non-RA patients4Cardiovascular manifestations of RA include accelerated atherosclerosis heart failure pericarditis myocarditis endocarditis rheumatoid nodules and amyloidosis Inflammation is an important mediator of endothelial dysfunction and is a key driver of cardiovascular risk and complications in patients with RA 3 The increased prevalence of atherosclerosis in RA seems to be associated with excess inflammatory burden and requires tailored screening strategies and management 1
Heart structural abnormalities are more prevalent in RA-patients than in general population such as pericarditis increased left ventricle mass and valvular disease 5 Left atrial LA dilation predicts atrial fibrillation and congestive heart failure It also increases the risk of developing thromboembolic events6
Echocardiography including transthoracic two and three-dimensional echocardiography Doppler imaging myocardial deformation and transesophageal echo is an established and widely available imaging technique for the identification of cardiovascular manifestations that are crucial for prognosis in rheumatic diseases Echocardiography is also important for monitoring the impact of drug treatment on cardiac function coronary microcirculatory function valvular function and pulmonary artery pressures 7
Left atrial volume index LAVI measured by two-dimensional 2D echocardiography is an accurate descriptor of LA volume and is recommended in the latest guidelines for the diagnosis of heart failure with preserved ejection fraction HFpEF 8 At present most previous studies focus solely on detecting the associations between baseline LAVI and clinical outcomes with few attentions paid to the prognostic value of LAVI alteration for HFpEF
Clinically RA patients typically present with a recent onset of tender and swollen joints morning joint stiffness generalized sickness symptoms as well as abnormal laboratory tests 2 The 28-joint disease activity score DAS28 is a widely used measure to assess disease activity in rheumatoid arthritis RA The DAS28-P index a derived proportion of the patient-reported components joint tenderness and patient global assessment within the DAS28 has been utilized as a discriminatory measure of non-inflammatory pain mechanisms in RA 9
Both ultrasound and MRI have been recommended for diagnosing and monitoring disease activity in RA patients 10 Musculoskeletal ultrasound is widely used to identify structural change and assess therapeutic response in RA Ultrasound analysis eg as high-resolution musculoskeletal ultrasound of inflamed joints allows imaging of synovial proliferation by grayscale as well as both active inflammation and neoangiogenesis by power Doppler In addition ultrasound can identify bone erosions 11 as well as subclinical synovitis that may result in radiographic disease progression even if the patient is in apparent clinical remission 12Due to these capabilities ultrasound is widely used in clinical practice as well as in clinical trials for the diagnosis of RA and the monitoring of disease states 13The advantages of ultrasound are its relatively low cost wide availability lack of contraindications and non-invasive real-time imaging capabilities Disadvantages are that ultrasound is considered an operator-dependent technology because of it being training-intensive in terms of both measurement and quality assessment 12
While being a very sensitive diagnostic tool to detect eg synovial hypertrophy or pannus formation before the occurrence of bone erosion routine usage of magnetic resonance imaging MRI techniques preferably contrasted in the diagnosis of RA is limited by cost factors and the limited capacity to image multiple joints in one measurement 2
In our study we will evaluate the LA function and dimensions parallel to the evaluation of disease activity in RA patients to detect possible association between disease activity and subclinical LA affection
Sample size was calculated using epi info program the following parameters were applied for observational cross sectional study Population size 150 seek care at Assiut university hospital proportion of left ventricular dysfunction among RA patients 59 5 design effect 1 and 95 confidence interval
The minimum estimated Sample size was 108 RA patients All participants will be subjected to the following history taking and clinical examination including Patients data will be collected included age at diagnosis gender residence occupation smoking and comorbidities and duration symptoms and signs of RA activity within the last 7 days If articular activity is present disease activity score-28 DAS-28 will be calculated based on the number of swollen or tender joint count and will be applied to establish RA activity
Patients will be subjected to transthoracic echocardiography including the following parameters will be measured
Left ventricular LV dimensions end diastolic and systolic dimensions and LV ejection fraction EF
Trans- mitral Doppler flow velocities including early E and lateA diastolic velocities EA ratio
LA anteroposterior diameter measure from 2D parasternal long axis view targeted M-mode
LA superior-inferior and medio-lateral diameters measure from the apical 4 chamber view
LA volume included
Maximal LA volume measure at the end of systole just before mitral valve opening at the end of the T wave on ECG Maximal LA volume is delivered from semi-automated tracing of the LA endometrium starting the measurements in the frame with the largest atrial dimensions corresponding to ventricular end systole just before the opening of the atrio-ventricular valves in perpendicular apical long axis planes
Minimal LA volume will be 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 will be obtained as the following LA maximal volume will be obtained from apical four-chamber and two-chamber views at end-systole through the modified Simpson disc method and then normalized to body surface area BSA to derive LAVI This will be assessed according to ASE guidelines then the patients according to the measures will be into four different levels normal 34 mlm2 mild dysfunction 34-41 mlm2 moderate dysfunction 42-48 mlm2 and severe dysfunction gt48 mlm2
Laboratory investigations will be obtained
Erythrocyte sedimentation rate ESR
C reactive protein CRP
Complete blood count CBC
Lipid profile test
Musculoskeletal ultrasonography will be done Ultrasound detected synovitis to be correlated with cardiac function
X ray of Hands will be done
Electrocardiogram ECG will be done 241- Type of the study Observational cross-sectional study 24 2- Study Setting rheumatology unit Internal Medicine Department at Assiut University Hospitals
24 3- Study subjects
1 Inclusion criteria
1 Patients with RA aged gt18 years and duration of RA disease gt1 year come to the rheumatology Internal medicine department or outpatient clinics at Assiut University Hospital
2 RA are diagnosed based on the ACREULAR 2010 rheumatoid arthritis classification criteria if a total score of 6 is needed to classify a patient as having definite RA
2 Exclusion criteria
1- Patients with known history of atherosclerotic heart disease 2- Patients with overlap syndrome 3- Patients with hypothyroidism Cushings syndrome anemia and severe hepatic or renal dysfunction
3 Sample size Calculation
sample size was calculated using epi info program the following parameters were applied for observational cross sectional study Population size 150 seek care at Assiut university hospital proportion of left ventricular dysfunction among RA patients 59 5 design effect 1 and 95 confidence interval
The minimum estimated Sample size was 108 RA patients 244 -Study tools in detail eg lab methods instruments steps chemicals A-History taking
1 All participants will be subjected to the following history taking and clinical examination including Patients data will be collected included age at diagnosis gender residence occupation smoking and comorbidities and duration symptoms and signs of RA activity within the last 7 days If articular activity is present disease activity score-28 DAS-28 will be calculated based on the number of swollen or tender joint count and will be applied to establish RA activity
2 Type of treatment received emphasizing current and former medications B- Laboratory investigations Erythrocyte sedimentation rate ESR
C reactive protein CRP
Complete blood count CBC
Lipid profile test
C- Other investigation
- Echocardiographic examination
Patients will be subjected to transthoracic echocardiography including the following parameters will be measured
Left ventricular LV dimensions end diastolic and systolic dimensions and LV ejection fraction EF
Trans- mitral Doppler flow velocities including early E and lateA diastolic velocities EA ratio
LA anteroposterior diameter measure from 2D parasternal long axis view targeted M-mode
LA superior-inferior and medio-lateral diameters measure from the apical 4 chamber view
LA volume included
Maximal LA volume measure at the end of systole just before mitral valve opening at the end of the T wave on ECG Maximal LA volume is delivered from semi-automated tracing of the LA endometrium starting the measurements in the frame with the largest atrial dimensions corresponding to ventricular end systole just before the opening of the atrio-ventricular valves in perpendicular apical long axis planes
Minimal LA volume will be 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 will be obtained as the following LA maximal volume will be obtained from apical four-chamber and two-chamber views at end-systole through the modified Simpson disc method and then normalized to body surface area BSA to derive LAVI This will be assessed according to ASE guidelines then the patients according to the measures will be into four different levels normal 34 mlm2 mild dysfunction 34-41 mlm2 moderate dysfunction 42-48 mlm2 and severe dysfunction gt48 mlm2
- Musculoskeletal ultrasonography Ultrasound detected synovitis to be correlated with cardiac function
- X ray of Hands
- Electrocardiogram ECG 245 -Research outcome measures
Primary main
Detect echocardiographic abnormalities in patients with rheumatoid arthritis
Detect subclinical echocardiographic changes of the LA dimensions and function in patients with rheumatoid arthritis
Evaluate the correlation between Rheumatoid arthritis and increased heart failure risk
Secondary outcome Subsidiary
Describe concurrent systemic comorbidities rheumatologic clinical activity serologic markers of rheumatoid arthritis and inflammatory activity
Evaluation of the LA function and dimensions parallel to the evaluation of disease activity in RA patients to detect possible association between disease activity and subclinical LA affection
Data management and analysis
Data collection The collected data will be revised coded tabulated and introduced to a PC
Computer software IBM_SPSS Statistical Package for Social Science Ver21 Standard version Copyright SPSS Inc 2011-2012 NY USA 2012
Statistical tests Data will be presented and suitable analysis will be done according to the type of data obtained for each parameter
iDescriptive statistics
1Description of qualitative variables is done by frequency and percentage 2Description of quantitative variables is in the form of mean and SD iiAnalytic statistics
1 χ2-test and Fishers exact test are used for comparison of qualitative variables with each other
2 Comparison between quantitative variables is carried out using Students t-test of two independent samples
3 For comparison of more than two quantitative groups analysis of variance F-test is used for categorical data
4 Significance level P is expressed as follows P value greater than 005 is not significant P value less than 005 is significant and P value less than 0001 is highly significant
5 Pearsons correlation coefficient is used to calculate the correlation between quantitative variables
Spearmans coefficient is calculated to determine the relationships between non parametric quantitative variables
RA patients remain at higher cardiovascular risk compared to non-RA patients4Cardiovascular manifestations of RA include accelerated atherosclerosis heart failure pericarditis myocarditis endocarditis rheumatoid nodules and amyloidosis Inflammation is an important mediator of endothelial dysfunction and is a key driver of cardiovascular risk and complications in patients with RA 3 The increased prevalence of atherosclerosis in RA seems to be associated with excess inflammatory burden and requires tailored screening strategies and management 1
Heart structural abnormalities are more prevalent in RA-patients than in general population such as pericarditis increased left ventricle mass and valvular disease 5 Left atrial LA dilation predicts atrial fibrillation and congestive heart failure It also increases the risk of developing thromboembolic events6
Echocardiography including transthoracic two and three-dimensional echocardiography Doppler imaging myocardial deformation and transesophageal echo is an established and widely available imaging technique for the identification of cardiovascular manifestations that are crucial for prognosis in rheumatic diseases Echocardiography is also important for monitoring the impact of drug treatment on cardiac function coronary microcirculatory function valvular function and pulmonary artery pressures 7
Left atrial volume index LAVI measured by two-dimensional 2D echocardiography is an accurate descriptor of LA volume and is recommended in the latest guidelines for the diagnosis of heart failure with preserved ejection fraction HFpEF 8 At present most previous studies focus solely on detecting the associations between baseline LAVI and clinical outcomes with few attentions paid to the prognostic value of LAVI alteration for HFpEF
Clinically RA patients typically present with a recent onset of tender and swollen joints morning joint stiffness generalized sickness symptoms as well as abnormal laboratory tests 2 The 28-joint disease activity score DAS28 is a widely used measure to assess disease activity in rheumatoid arthritis RA The DAS28-P index a derived proportion of the patient-reported components joint tenderness and patient global assessment within the DAS28 has been utilized as a discriminatory measure of non-inflammatory pain mechanisms in RA 9
Both ultrasound and MRI have been recommended for diagnosing and monitoring disease activity in RA patients 10 Musculoskeletal ultrasound is widely used to identify structural change and assess therapeutic response in RA Ultrasound analysis eg as high-resolution musculoskeletal ultrasound of inflamed joints allows imaging of synovial proliferation by grayscale as well as both active inflammation and neoangiogenesis by power Doppler In addition ultrasound can identify bone erosions 11 as well as subclinical synovitis that may result in radiographic disease progression even if the patient is in apparent clinical remission 12Due to these capabilities ultrasound is widely used in clinical practice as well as in clinical trials for the diagnosis of RA and the monitoring of disease states 13The advantages of ultrasound are its relatively low cost wide availability lack of contraindications and non-invasive real-time imaging capabilities Disadvantages are that ultrasound is considered an operator-dependent technology because of it being training-intensive in terms of both measurement and quality assessment 12
While being a very sensitive diagnostic tool to detect eg synovial hypertrophy or pannus formation before the occurrence of bone erosion routine usage of magnetic resonance imaging MRI techniques preferably contrasted in the diagnosis of RA is limited by cost factors and the limited capacity to image multiple joints in one measurement 2
In our study we will evaluate the LA function and dimensions parallel to the evaluation of disease activity in RA patients to detect possible association between disease activity and subclinical LA affection
Sample size was calculated using epi info program the following parameters were applied for observational cross sectional study Population size 150 seek care at Assiut university hospital proportion of left ventricular dysfunction among RA patients 59 5 design effect 1 and 95 confidence interval
The minimum estimated Sample size was 108 RA patients All participants will be subjected to the following history taking and clinical examination including Patients data will be collected included age at diagnosis gender residence occupation smoking and comorbidities and duration symptoms and signs of RA activity within the last 7 days If articular activity is present disease activity score-28 DAS-28 will be calculated based on the number of swollen or tender joint count and will be applied to establish RA activity
Patients will be subjected to transthoracic echocardiography including the following parameters will be measured
Left ventricular LV dimensions end diastolic and systolic dimensions and LV ejection fraction EF
Trans- mitral Doppler flow velocities including early E and lateA diastolic velocities EA ratio
LA anteroposterior diameter measure from 2D parasternal long axis view targeted M-mode
LA superior-inferior and medio-lateral diameters measure from the apical 4 chamber view
LA volume included
Maximal LA volume measure at the end of systole just before mitral valve opening at the end of the T wave on ECG Maximal LA volume is delivered from semi-automated tracing of the LA endometrium starting the measurements in the frame with the largest atrial dimensions corresponding to ventricular end systole just before the opening of the atrio-ventricular valves in perpendicular apical long axis planes
Minimal LA volume will be 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 will be obtained as the following LA maximal volume will be obtained from apical four-chamber and two-chamber views at end-systole through the modified Simpson disc method and then normalized to body surface area BSA to derive LAVI This will be assessed according to ASE guidelines then the patients according to the measures will be into four different levels normal 34 mlm2 mild dysfunction 34-41 mlm2 moderate dysfunction 42-48 mlm2 and severe dysfunction gt48 mlm2
Laboratory investigations will be obtained
Erythrocyte sedimentation rate ESR
C reactive protein CRP
Complete blood count CBC
Lipid profile test
Musculoskeletal ultrasonography will be done Ultrasound detected synovitis to be correlated with cardiac function
X ray of Hands will be done
Electrocardiogram ECG will be done 241- Type of the study Observational cross-sectional study 24 2- Study Setting rheumatology unit Internal Medicine Department at Assiut University Hospitals
24 3- Study subjects
1 Inclusion criteria
1 Patients with RA aged gt18 years and duration of RA disease gt1 year come to the rheumatology Internal medicine department or outpatient clinics at Assiut University Hospital
2 RA are diagnosed based on the ACREULAR 2010 rheumatoid arthritis classification criteria if a total score of 6 is needed to classify a patient as having definite RA
2 Exclusion criteria
1- Patients with known history of atherosclerotic heart disease 2- Patients with overlap syndrome 3- Patients with hypothyroidism Cushings syndrome anemia and severe hepatic or renal dysfunction
3 Sample size Calculation
sample size was calculated using epi info program the following parameters were applied for observational cross sectional study Population size 150 seek care at Assiut university hospital proportion of left ventricular dysfunction among RA patients 59 5 design effect 1 and 95 confidence interval
The minimum estimated Sample size was 108 RA patients 244 -Study tools in detail eg lab methods instruments steps chemicals A-History taking
1 All participants will be subjected to the following history taking and clinical examination including Patients data will be collected included age at diagnosis gender residence occupation smoking and comorbidities and duration symptoms and signs of RA activity within the last 7 days If articular activity is present disease activity score-28 DAS-28 will be calculated based on the number of swollen or tender joint count and will be applied to establish RA activity
2 Type of treatment received emphasizing current and former medications B- Laboratory investigations Erythrocyte sedimentation rate ESR
C reactive protein CRP
Complete blood count CBC
Lipid profile test
C- Other investigation
- Echocardiographic examination
Patients will be subjected to transthoracic echocardiography including the following parameters will be measured
Left ventricular LV dimensions end diastolic and systolic dimensions and LV ejection fraction EF
Trans- mitral Doppler flow velocities including early E and lateA diastolic velocities EA ratio
LA anteroposterior diameter measure from 2D parasternal long axis view targeted M-mode
LA superior-inferior and medio-lateral diameters measure from the apical 4 chamber view
LA volume included
Maximal LA volume measure at the end of systole just before mitral valve opening at the end of the T wave on ECG Maximal LA volume is delivered from semi-automated tracing of the LA endometrium starting the measurements in the frame with the largest atrial dimensions corresponding to ventricular end systole just before the opening of the atrio-ventricular valves in perpendicular apical long axis planes
Minimal LA volume will be 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 will be obtained as the following LA maximal volume will be obtained from apical four-chamber and two-chamber views at end-systole through the modified Simpson disc method and then normalized to body surface area BSA to derive LAVI This will be assessed according to ASE guidelines then the patients according to the measures will be into four different levels normal 34 mlm2 mild dysfunction 34-41 mlm2 moderate dysfunction 42-48 mlm2 and severe dysfunction gt48 mlm2
- Musculoskeletal ultrasonography Ultrasound detected synovitis to be correlated with cardiac function
- X ray of Hands
- Electrocardiogram ECG 245 -Research outcome measures
Primary main
Detect echocardiographic abnormalities in patients with rheumatoid arthritis
Detect subclinical echocardiographic changes of the LA dimensions and function in patients with rheumatoid arthritis
Evaluate the correlation between Rheumatoid arthritis and increased heart failure risk
Secondary outcome Subsidiary
Describe concurrent systemic comorbidities rheumatologic clinical activity serologic markers of rheumatoid arthritis and inflammatory activity
Evaluation of the LA function and dimensions parallel to the evaluation of disease activity in RA patients to detect possible association between disease activity and subclinical LA affection
Data management and analysis
Data collection The collected data will be revised coded tabulated and introduced to a PC
Computer software IBM_SPSS Statistical Package for Social Science Ver21 Standard version Copyright SPSS Inc 2011-2012 NY USA 2012
Statistical tests Data will be presented and suitable analysis will be done according to the type of data obtained for each parameter
iDescriptive statistics
1Description of qualitative variables is done by frequency and percentage 2Description of quantitative variables is in the form of mean and SD iiAnalytic statistics
1 χ2-test and Fishers exact test are used for comparison of qualitative variables with each other
2 Comparison between quantitative variables is carried out using Students t-test of two independent samples
3 For comparison of more than two quantitative groups analysis of variance F-test is used for categorical data
4 Significance level P is expressed as follows P value greater than 005 is not significant P value less than 005 is significant and P value less than 0001 is highly significant
5 Pearsons correlation coefficient is used to calculate the correlation between quantitative variables
Spearmans coefficient is calculated to determine the relationships between non parametric quantitative variables
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None