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C Pdemo


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Some of prior work

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C Pdemo

  1. 1. Use of Cardiac Pacing for HF and AF Don W. Wallick, PhD
  2. 2. Atrial Fibrillation <ul><li>AF is the most prevalent persistent cardiac arrhythmia in USA. </li></ul><ul><li>AF result in supraventricular tachycardia. </li></ul><ul><li>Solutions </li></ul><ul><ul><li>Rhythm control (restore sinus rhythm) </li></ul></ul><ul><ul><li>Rate control (control ventricular rate) </li></ul></ul>
  3. 3. Coupled Pacing –Rate Control 1 st Pacing Paradigm
  4. 4. Concept of Coupled Pacing during AF Electrically Activating the Ventricles after a Specific Delay Atrium Ventricle AV Node Created by Yamada used in Yanulis et al. Ann. Thor. Surg. 86: 984-8, 2008                       Atrium Ventricle AV Node
  5. 5. AF Can Lead to Ventricular Tachycardia <ul><li>AV node is not a perfect filter. </li></ul><ul><li>During AF, Rapid Irregular Ventricular Contractions can occur. </li></ul><ul><li>These Ventricular Contractions sometimes fail to eject blood. </li></ul><ul><li>Ventricular Tachycardia can lead to HF. </li></ul><ul><li>Coupled Pacing, which results in little to no mechanical contractions, blocks approximately half of the supraventricular activations leading to slower stronger ventricular contractions. </li></ul>
  6. 6. Animal Preparation for Acute AF Conductance/ pressure catheter to produce PV loops Ao Pressure catheter RA electrode- used to induce AF RV electrode Sense RV activation then apply CP LA Pressure catheter Epicardial Echocardiography
  7. 7. Representative P-V loops during Acute AF AF + CP 0 20 40 60 80 100 120 140 160 0 10 20 30 40 AF 0 20 40 60 80 100 120 140 160 0 10 20 30 40 LV volume (ml) LV volume (ml) LV pressure (ml) Modified from Yamada et al. Am. J. Physiol. 285: H2630-8, 2003
  8. 8. Advantages of CP <ul><li>CP has a positive inotropic effect while it slows the rate of ventricular contraction. </li></ul><ul><li>The stimuli can be applied via a right ventricular pacing lead connected to a modified clinical pacemaker programmed with the proper algorithms. </li></ul><ul><li>Immediate and persistent effects. </li></ul><ul><li>Its effect can be controlled. </li></ul>
  9. 9. Areas of Concern <ul><li>Is there an increase risk of the ventricular arrhythmias during CP? </li></ul><ul><li>Is there an increase in oxygen consumption during CP? </li></ul>
  10. 10. Effect of Altering the time delay for CP application
  11. 11. Representative Responses Modified from Yamada et al. Heart Rhythm 3: 722-7, 2006
  12. 12. Summary Concerning Possible Arrhythmias Coupled pacing is still effective in rate reduction and pump function even after longer time delays (220ms) compared to the shorter delays (180ms). An established embolization model (diffuse infarction) was used to test whether the therapy can be safely applied in post-infarcted state. Coupled pacing may be safer than previously believed.
  13. 13. Areas of Concern <ul><li>Is there an increase risk of the ventricular arrhythmias during CP? </li></ul><ul><li>Is there an increase in oxygen consumption (MVO 2 ) during CP? </li></ul>
  14. 14. Paired Pacing <ul><li>Paired pacing increases oxygen consumption (7-90%, mean 35%) </li></ul><ul><li>Paired pacing increases coronary blood flow </li></ul>Hoffman B, et al. Bull N Y Acad Med 1965;41:498-535 Ross J, Braunwald, et al. Circ Res 1965;16:332-342 Katz L, et al. Bull N Y Acad Med 1965;41:428-461 Chardack W, et al. Bull N Y Acad Med 1965;41:462-480
  15. 15. Paired Pacing vs Coupled Pacing P P P P P P P’ P P’ P P’ P P’ P P’ Paired Stimulation S S S S S S S S S Coupled Pacing P P’ P P’ Art Press Art Press P’ P’ P’ P’
  16. 16. <ul><li>Paired Pacing </li></ul><ul><li>Constant pacing from right ventricular apex (P) results in dyssynchronous contractions. </li></ul><ul><li>P’ increase contractility via increase release of calcium. </li></ul><ul><li>Increases in contractility w/o reduction in rate of ventricular contractions dramatically increase oxygen consumption. </li></ul><ul><li>Coupled Pacing </li></ul><ul><li>Normal supraventricular electrical activations (S) results in synchronized ventricular contractions. </li></ul><ul><li>Coupled pacing (P’) blocks half of the supraventricular activations, resulting in the reduction in rate of ventricular contractions. </li></ul><ul><li>P’ increases contractility via in release of calcium. </li></ul><ul><li>Reduction in ventricular contractile rate minimizes the increase in oxygen consumption as shown in our next series of experiments. </li></ul>
  17. 17. Acute Cardiac Energetics Study
  18. 18. Animal preparation Aortic pressure catheter LA pressure catheter LV pressure catheter Aortic flow probe Coronary flow probe Coronary Sinus RA electrode RV electrode
  19. 19. Acute Study Protocol α - chloralose anesthesia Stage 1: Baseline Sinus Rhythm Stage 2: Atrial Fibrillation Stage 3: Acute Heart Failure Stage 4: Acute Heart Failure/ Atrial Fibrillation SR AF HF HF/AF Rapid Atrial Pacing +3-5% Isoflurane CP Modified from Yamada et al. Am. J. Physiol. 287: H2016-22, 2004
  20. 20. Effects of CP External Cardiac Work Myocardial Oxygen Consumption (ml/min) (J/min) 12 0 5 10 15 20 25 30 0 2 4 6 8 10 NS NS NS NS p<0.001 p<0.01 NS p<0.001 SR AF HF HF/AF SR AF HF HF/AF Coupled Pacing Modified from Yamada et al. Am. J. Physiol. 287: H2016-22, 2004 Off On Off On Off On Off On Off On Off On Off On Off On
  21. 21. Myocardial Efficiency (%) 0 5 10 15 20 25 30 SR AF HF HF/AF Coupled Pacing Effects of CP Modified from Yamada et al. Am. J. Physiol. 287: H2016-22, 2004 NS p<0.01 p<0.01 p<0.05 Off On Off On Off On Off On
  22. 22. Summary Concerning Increase in MVO 2 <ul><li>Due to the reduction in ventricular contractile rate while there was an increase in strength of contractions, coupled pacing acutely increased external work of the left ventricle to a greater degree than an increase in MVO 2 . </li></ul><ul><li>This therapy acutely improves myocardial efficiency. </li></ul>
  23. 23. Effects of Sustained CP on Chronic AF <ul><li>Can the effects of CP be sustained? </li></ul><ul><li>Are these effects similar to what we found in our acute experiments? </li></ul>
  24. 24. <ul><li>Pacemaker Implantation Procedure </li></ul><ul><li>2 endocardial pacemaker leads </li></ul><ul><li>2 standard dual chamber pacemakers </li></ul><ul><li>2 custom Y lead adapters </li></ul>
  25. 25. Experimental Setup Modified from Yanulis et al .Ann. Thor. Surg. 86: 984-8, 2008
  26. 26. Pacing Protocol <ul><li>Rapid right ventricular pacing (240 bpm) using the DOO mode for 2-4 wks until LVEF decreased by at least 20%. Ventricular pacemaker turned off (from DOO to ODO). Rapid right atrial pacing at 20 bpm above sinus rate (AOO mode). Switching pacing mode from AOO to DOO with AV interval setting was adjusted that stimuli from the ventricular port would still capture atrial tissue. Weekly ECG measurements were obtained. Atrial pacemaker was turned off (DOO to ODO) and AF continued after 2-4 wks of pacing. Ventricular pacemaker turned on (DDD) with AV interval setting used for the CP delay (160-220 ms) for 4 wks. </li></ul>
  27. 27. Effects of Chronic AF and Coupled Pacing on Cardiac Volumes (Echocardiographic measurements) Modified from Yanulis et al. Ann. Thor. Surg. 86: 984-8, 2008
  28. 28. Modified from Yanulis et al. Ann. Thor. Surg. 86: 984-8, 2008
  29. 29. Conclusions of this Chronic Study <ul><li>The tachycardia of chronic AF resulted in enlarged ventricular volumes (remodeling). </li></ul><ul><li>Sustained CP reduced the rate of ventricular contractions. </li></ul><ul><li>Sustained CP reduced ventricular volumes (reversed remodeling). </li></ul>
  30. 30. CRT + CP Pacing 2 nd Pacing Paradigm
  31. 31. Atrial Fibrillation in Heart Failure Patients <ul><li>AF and HF frequently coexist </li></ul><ul><li>HF promotes AF and AF may cause or aggravate HF </li></ul><ul><li>25 % HF patients also have AF </li></ul>
  32. 32. LBBB in Heart Failure Patients <ul><li>34% of HF patients have LBBB. </li></ul><ul><li>30% of above these patients also have AF. </li></ul>
  33. 33. Current Pacing Therapies <ul><li>CRT: </li></ul><ul><ul><li>#1 Pacemaker generator </li></ul></ul><ul><ul><li>#2 right atrial pacer wire </li></ul></ul><ul><ul><li>#3 right ventricular pacer wire </li></ul></ul><ul><ul><li>#4 coronary sinus (LV) )pacer wire. </li></ul></ul>Source:
  34. 34. <ul><li>CRT is effective in many HF patients w/ LBBB. </li></ul><ul><li>CRT is not effective in some HF patients (non-responders) despite resynchronization even when the patient remain in sinus rhythm (30%). </li></ul><ul><li>CRT can only be effective if the ventricular rate is controlled during AF (atrial tracking). </li></ul><ul><li>CP added to CRT could be an effective means of rate control when AF would occur. </li></ul>Complexities of CRT
  35. 35. Animal preparation RA electrode RV electrode Epicardial Echocardiography LV electrode Vagal electrode
  36. 36. Right atrium Right ventricle VS Left ventricle VS RR 127 ±17 cpm 70 ±13 ms Baseline N=6 Sinus Rhythm Step 1 VRMC QRS duration Experimental protocol Atrial Fibrillation Step 2 Step 3 Step 4 Step 5 116±17 cpm 65 ±11 ms CRT+ CP N=6 103 ±14 cpm 76 ±10 ms CRT-VS N=3 232 ±15 cpm 61 ±9 ms CRT N=6 219 ±39 cpm 110 ±23 ms RV pacing N=6 213±32 cpm 63 ±19 ms Atrial pacing N=6 CP CRT
  37. 38. Conclusions <ul><li>CRT+CP may convert non-responders to responders in HF patients in sinus rhythm via a positive inotropic effect. </li></ul><ul><li>The addition of CP to CRT would permit effective CRT to continue via its effective rate control mechanism despite if AF and the subsequent rapid ventricular contractions should occur. </li></ul>