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Endothelial dysfunction screening tct 2003 - 2

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Endothelial dysfunction screening tct 2003 - 2

  1. 1. Measurement of Endothelial Dysfunction for Detection of Vulnerable Plaque and the Vulnerable Patient Morteza Naghavi, MD AHA – 2003 Orlando, FL
  2. 2. From Endothelial Failure to Myocardial Failure The Trail of Heart Disease
  3. 3. •Endothelial Injury Precedes Atherosclerosis •Endothelial Failure Precedes Athero-thrombosis
  4. 4. Endothelial Failure Uncontrolled Endothelial Injury Subclinical Endothelial Failure Clinical Endothelial Failure Sustained Endothelial Dysfunction Vulnerable Plaque / Vulnerable Patient ACS – MI – Thrombotic Stroke
  5. 5. EF Screening
  6. 6. The Ideal Test for VP Screening • Non-Invasive • Easy (no technical knowledge) • Inexpensive (< $5 per each test, $1?!) • Self-Administered (out-of-hospital: public places and home) • Reproducible • Changes with the course of disease and therapy (predictor of disease and response to therapy just like blood pressure monitoring)
  7. 7. Endothelial Dysfunction a Surrogate Marker of CHD Coronary endothelial dysfunction has been associated in many experimental studies with: - CHD Risk Factors (LDL, CRP,..) - CHD Subclinical Markers (IMT, CCS) - First Event (CHD and Stroke) - Recurrent CHD Events - Response to Therapy (Statin, ACE…) - And genetic susceptibility
  8. 8. Endothelial Function Test ? The Near Ideal Test for VP Screening
  9. 9. The Biology of Endothelial Function
  10. 10. Molecule of the year 1995 and Nobel Prize of 1998
  11. 11. Nobel Prize Experiment
  12. 12. Techniques for Measurement of Endothelial Dysfunction • Brachial artery imaging with high- resolution ultrasound during reactive hyperemia is now a widely used method of determining peripheral vascular function. - arm cuff inflation (suprasystolic) - ischemia reduces distal resistance and opening the cuff induces stretch in the artery - imaging the diameter of the artery along with measuring the peak flow defines endothelial function.
  13. 13. The Pioneering Work • Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility KE Sorensen, DS Celermajer, DJ Spiegelhalter, D Georgakopoulos, J Robinson, O Thomas and JE Deanfield Cardiothoracic Unit, Hospital for Sick Children, London. British Heart Journal, Vol 74, 247-253, Copyright © 1995 Heart
  14. 14. Techniques for Measurement of Endothelial Dysfunction • Venous occlusion plethysmography, another method for evaluating peripheral vasomotor function, involves measuring volume changes in the forearm by mercury strain gauges during hyperemia. • Invasive and cumbersome
  15. 15. Techniques for Measurement of Endothelial Dysfunction • Tissue Doppler imaging or flowmetry of hand continuously showing skin perfusion before and after hyperemia. • Single fiber / point Doppler measurement of flow at finger tip. • Not-Inexpensive!
  16. 16. Tissue Doppler Imaging of Skin Perfusion >> Doppler Flowmetry ⇓
  17. 17. Techniques for Measurement of Endothelial Dysfunction • Peripheral arterial tonometry (PAT) measures changes in the volume of finger as indicator of changes in blood flow which reflects changes in the diameter of brachial artery udring hyperemia. • Non-Invasive • Not Inexpensive • Not Self-Administered
  18. 18. PAT • PAT involves the use of a clothespin-like device placed over your fingertip to measure pulsaltile changes in arterial blood volume. The measurements are then processed by a variety of mathematical algorithms and standardized signal processing techniques.
  19. 19. Our Technique for Measurement of Endothelial Dysfunction Digital thermal monitoring • Monitors the change of temperature as an indicator of change in flow • The slope and pattern of temperature change at finger tips before and after release of occlusion correlate with brachial vasoreactivity • Cheap • Self-Administered • Easily adaptable in a home-based blood pressure monitoring device
  20. 20. We have tested different prototypes
  21. 21. Schematic Designs Blood pressure cuff Left hand Glove T1 T7 T5 T4 T3 T8 T2 T6 T1~T8 are the temperature sensors located as shown in the figure Lead wire bundle from the temperature sensors
  22. 22. A Home-Based Self-Administered Endothelial Dysfunction And Blood Pressure Monitoring Device ENDYS; The Ultimate Design
  23. 23. Experimental Procedure 1. Attach the thermistor to the distal palmar pad of the middle finger of the hand, and tape it. 2. Allow the initial temperature before the occlusion is started to stabilize for at least 2 minutes. 3. Then start the occlusion of the blood by placing the blood pressure cuff on the arm at about 200mm of Hg. 4. Note the temperature continuously right from the stabilization of the temperature. Keep the occlusion for about 5 minutes. 5. Then suddenly release the occlusion after 5 minutes and keep on monitoring the increase in the temperature of the finger for about another 3 minutes. 6. Plot the readings of the temperature against the time and do the further analysis from the curve obtained.
  24. 24. Same person, same position, different time 85.1 87.1 89.1 91.1 93.1 95.1 0 100 200 300 400 500 600 700 800 Timte (s) Temperature(F) Case 4 Middle finger (200mm Hg, SELF) Case 6 Middle finger (200mm Hg, SELF) Case 7 Middle finger (200mm Hg, SELF)
  25. 25. Temperature Monitoring of Middle Fingertip Before and After Releasing Blood Pressure Cuff 84.1 86.1 88.1 90.1 92.1 94.1 0 100 200 300 400 500 600 Time (s) Temperature(F)
  26. 26. Curve analysis with curve function y = -2E-14x 6 + 3E-11x 5 - 2E-08x 4 + 4E-06x 3 - 0.0006x 2 + 0.021x + 94.47 R 2 = 0.973586.6 87.6 88.6 89.6 90.6 91.6 92.6 93.6 94.6 95.6 0 100 200 300 400 500 600 700 Time in second TempinF Case 3 Middle finger (200mm Hg, SWAPNIL) Poly. (Case 3 Middle finger (200mm Hg, SWAPNIL)) Occlusion Created Occlusion released Slope = - 0.020878 F/s Slope = 0.053053 F/s
  27. 27. The slope or rate of decrease in the temperature after the occlusion is created is - 0.020878 F/s The slope or rate of increase in the temperature after the release of occlusion is 0.053053 F/s. The rate of increase in the temperature is 2.541046 times faster than the earlier rate.
  28. 28. The equation for the slope of the regression line is: Slope = { n * [ SUM (x*y)]} – { (SUM x ) * (SUM y ) } / {n * (SUM x^2) –(SUM x )^2} Calculates the least squares fit through points by using the following equation: y = a*x^6 + b*x^5 + c*x^4 + d*x3 + e*x^2 + f*x + g where a,b,…g are constants.
  29. 29. Case No. Rate of fall (F/s) (Slope after occlusion) Rate of rise (F/s) (Slope after release of occlusion) Rise/Fall % Increase 1 0.020878 0.053053 2.541046 154.10 2 0.018757 0.034860 1.858543 85.85 3 0.022776 0.034980 1.535827 53.58 4 0.025814 0.034426 1.333591 33.36 5 0.023871 0.071957 3.014388 201.44 6 0.013320 0.032943 2.473220 147.32 7 0.012770 0.047234 3.698723 269.87 8 0.03349143 0.091881 2.743408 174.34
  30. 30. The Challenge: Intra-individual Variability of Endothelial Function Measurements Similar to blood pressure variability, measurement of barchial vasoreactivity may show marked variations (diurenal, postprandial, positional, etc) The answer to this problem will be similar to the answer to blood pressure measurement namely multiple measurements and standardized settings for measurement.
  31. 31. Next steps • Validate the digital thermal monitoring with ultrasound based measurement. • Correlate with Framingham risk score and emerging risk factors (CRP, PLAC,…) • Correlate with other subclinical markers such as coronary calcium score and carotid IMT
  32. 32. From the Bottom to the Top go EF Screening
  33. 33. EF Screening Serum Screening CT Screening Intravascular Screening (coronary EF, TCFA, …)

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