Methodology
ASSUMPTION
Phosphodiesterase inhibitors will reverse the endothelial dysfunction in CTD patients with PAH which can be predicted from FMD of brachial artery.
STUDY DESIGN
Descriptive Prospective study
STUDY PERIOD
18 months from March 2017 to September 2018
INCLUSION CRITERIA
All CTD patients with diagnosed pulmonary artery hypertension with NYHA II/III.
EXCLUSION CRITERIA
CTD with PAH in NYHA IV.
Congenital heart diseases.
Structural heart diseases- Valvular and Myocardial diseases.
Prior Respiratory diseases.
History of Deep Vein Thrombosis (DVT) and Pulmonary Thromboembolism.
Poor echocardiographic window.
SAMPLE PROCEDURE
After obtaining proper informed consent from patient/ patient’s relative for inclusion in the study, demographic data will be collected and findings of clinical examinations and echocardiographic findings will be recorded based on a structural format.
DATA COLLECTION AND STUDY METHOD
CTD patients with suspected or diagnosed pulmonary hypertension to be started on phosphodiesterase inhibitors are included in the study.
FMD in brachial artery is measured • before starting PDE-5i • after starting PDE-5i for 1 week • after 6 months of PDE-5i
Follow up after 6 months will also have echocardiographic assessment of the right heart along with FMD.
FMD will be measured with a 9Mhz linear array transducer (GE 9-LD) on a GE VIVID E-9 ultrasound/ECHO machine. Flow stimulus is created in the artery by a sphygmomanometer.
Patients were asked to avoid smoking, limiting vitamin supplementation, cessation of medications (β blockers, PDE-5i) and caffeine use 12 hours before first examination. They were asked to come well rested without any prior exercise prior to the FMD measurement.
Image acquisition
The subject is positioned supine with the arm in a comfortable position for imaging the brachial artery. The brachial artery is imaged in longitudinal sections from 1 to 5 cm above the elbow above the antecubital fossa with a 9 MHz linear array transducer, the skin surface is marked and the arm is kept in the same po- sition during the study. A segment with clear anterior and posterior intimal interfaces between the lumen and vessel wall is selected for continuous 2D gray scale imaging. During image acquisition, anatomic landmarks such as veins and fascial planes are noted to help maintain the same image of the artery throughout the study. Color flow imaging is used to verify the brachial artery and to locate collateral vessels that may serve as landmarks. The diameter of the brachial artery should be measured from longitudinal images in which the lumen-intima interface is visualized on the near (an- terior) and far (posterior) walls. The diameter is measured once before starting PDE-5i, after starting PDE-5i in 1 week and 6 months.4,6
Endothelium-dependent FMD
To create a flow stimulus in the brachial artery, a sphygmomanometric cuff is first placed either above the antecubital fossa. A baseline rest image is acquired, and blood flow is estimated by time-averaging the pulsed Doppler velocity signal obtained from a midartery sample volume.
Arterial occlusion is created by cuff inflation to suprasystolic pressure, at least 50 mm Hg above systolic pressure to occlude arterial inflow for 5 minutes. The longitu- dinal image of the artery is recorded continuously from 30 s before to 2 min after cuff deflation. A midartery pulsed Doppler signal is obtained upon immediate cuff release and no later than 15 s after cuff deflation to assess hyperemic velocity.
Procedure
At the first visit, brachial artery diameter will be measured as described above, following that FMD of brachial artery will be taken using a sphygmomanometer. Single measurement will be taken. This method will be repeated after 1 week and 6 months of starting PDE-5i.
SAMPLE SIZE4
Sample size was calculated by the following formula as
npairs = [Z1-α/2 + Z1- β]2 + Z12-α/2
Δ 2 2
Δ = M2-M1
a
a= a1+a2
2
a1 = 3.18
a2 = 2.42
M1 = 8.07 (FMD of brachial artery at baseline)
M2 = 6.01 (FMD of brachial artery after 3 months)
α = 0.05
Power = 90% = 1.282
n= 21 pairs
Where,
N – Sample size
a1= standard deviation in the pretest
a2= standard deviation in the posttest
M1= pretest mean
M2= Posttest mean
ANALYSIS
Descriptive statistical analysis will be carried out. Results on continuous measurements are presented on Mean ± SD (Min-Max) and results on categorical measurements are presented in Number (%). Significance is assessed at 5 % level of significance. Chi-square/ Fisher Exact, paired t-test will be used to find the significance of study parameters on categorical scale between two or more groups. Diagnostic statistics viz. Sensitivity, Specificity, PPV and NPV will be calculated.