EP Summit 2014: Can We Do Anything if CRT Isn’t Helping? “Non-Responders”


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Kevin Jackson, MD

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EP Summit 2014: Can We Do Anything if CRT Isn’t Helping? “Non-Responders”

  1. 1. Cardiac Resynchronization Therapy: Managing Non-responders Kevin Jackson, M.D. Director, Duke CRT Center Clinical Cardiac Electrophysiology Duke University Medical Center
  2. 2. Cardiac Resynchronization Therapy •  1984 – De Teresa •  1994 – Cazeau •  1998 – Daubert Large RCT’s of CRT – 2002 to present MIRACLE (n=453) CONTAK-CD (n=490) COMPANION (n=1520) CARE-HF (n=813) REVERSE (n=610) MADIT-CRT (n=1820) RAFT (n=1798)
  3. 3. Mortality Benefit with CRT 40% 36% 34% 30% 25% 20% 10% 0% COMPANION CARE-HF NYHA Class III/IV RAFT NYHA Class II/III Slide adapted from COMPANION (Bristow MR, et al. N Engl J Med. 2004 ;350(21):2140-50), CARE-HF (Ghio S, et al.Eur J Heart Fail. 2009 ;11(5):480-8) , RAFT (Tang A, et al. N Engl J Med 2010;363(25):2385-95)
  4. 4. rds 2/3 “Only of patients respond to CRT”
  5. 5. Defining CRT Response Smaller volumes = better survival From Fornwalt BK, et al. Circulation. 2010;121:1985-1991, Yu CM, et al. Circulation. 2005;112:1580-1586, and Solomon S, et al. Circulation 2010, 122:985-992
  6. 6. Reverse Remodelling – When to Measure? 6 months Verhaert D, et al. J Am Coll Cardiol 2010;55:1788–95
  7. 7. Placebo Effect 70 CRT 61 Placebo 60 50 Overall 49 38 40 30 23 30 19 20 10 0 NYHA (%) Δ LVESV Slide adapted from CARE-HF (Ghio S, et al.Eur J Heart Fail. 2009 May;11(5):480-8) and COMPANION (Bristow MR, et al. N Engl J Med. 2004 May 20;350(21):2140-50)
  8. 8. Response to CRT is Dependent Upon Multiple Factors •  LBBB >> RBBB •  QRS > 150 msec Electrical •  Dyssynchrony •  Transmural scar •  Mitral regurgitation Mechanical Response Biologic •  “Fetal genes” •  Calcium handling Genetic •  Female gender •  Non-ischemic CM Vanderheyden M, et al. J Am Coll Cardiol 2008;51:129–36; Moss AJ et. al. N Engl J Med. 2009;361:1329–1338.
  9. 9. Percentage of Nonresponder Patients with These Findings There Are Multiple Causes of NonResponse to CRT 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Suboptimal AV Timing Arrhythmia Anemia Suboptimal LV Lead Position Mullens W, et al. J Am Coll Cardiol. 2009;53:765-773. Mullens W, et al. J Am Coll Cardiol 2009;53:765–73 < 90% Suboptimal Persistent Underlying Biventricular Medical Mechanical Narrow Pacing Therapy Dyssynchrony QRS Compliance Primary RV Issues Dysfunction
  10. 10. Approach to Improving Response to CRT Patient Selection Pre-Implant Imaging Implant Technique Implant Acute Response Optimization Post-Implant Patient Management
  11. 11. Pre-CRT Evaluation to Optimize Response Echocardiographic speckle strain imaging can be used to identify the latest activated LV wall
  12. 12. Identification of Regions of Transmural Scar by cardiac MRI or Echo Cut-off of <16.5% radial strain by echo may identify regions of dense transmural scar Delgado, V et al. Circulation. 2011;123:70-78
  13. 13. TARGET Results: 70% versus 55% response rate (p=0.031) Khan, FZ et al. J Am Coll Cardiol 2012;59:1509–18
  14. 14. STARTER Trial – Speckle Tracking Assisted Resynchronization Therapy for Electrode Region Event-free survival is significantly improved in the echo-guided group (HR = 0.48, p=0.006) Saba S, et al. Circ Heart Failure. Epub ahead of print
  15. 15. Re-timing of Severe Baseline Dyssynchrony in STARTER Trial 24% of patients in the echo-guided arm had the LV lead targeted to non-lateral or posterolateral region Saba S, et al. Circ Heart Failure. Epub ahead of print
  16. 16. Need to Merge Information on Latest Activation with Available Anatomy Saba S, et al. Circ Heart Failure. Epub ahead of print
  17. 17. Improvement in Techniques and Tools to Enable Targeted Lead Implantation
  18. 18. The Telescoping System – Directional and Delivery Catheters to Improve Implant Sheath Delivery Directional Wire
  19. 19. Optimal* LV Lead Placement Improved with Telescoping Approach P = 0.01 87% 75% Optimal* Non-optimal * Optimal LV lead position defined as posterior/lateral and basal/mid segments 35% 13% Standard Jackson KP, et al. Pacing Clin Electrophysiol. 2013. epub ahead of print Interventional
  20. 20. How to Improve Response in PostImplant Patients Device Optimization Timing Optimization Patient Optimization RESPONSE
  21. 21. Outcomes Improved in Patients with Near 100% BiV Pacing Early data showed decline at < 93% BiV pacing; Recent, larger cohort data at < 98.5% BiV pacing Koplan BA, et al. J Am Coll Cardiol 2009;53:355–60; Hayes DL, et al. Heart Rhythm 2011;8:1469 –1475
  22. 22. A Significant Percentage of Patients Do Not Achieve Optimal BiV Pacing % Reasons for < 100% pacing •  Atrial fibrillation •  PVC’s •  Competitive AV nodal conduction In a cohort of > 80,000 patients, 40.7% exhibited less than 98% BiV pacing Cheng A, et al. Circ Arrhythm Electrophysiol. 2012;5:884-888k
  23. 23. Optimization of Medications After CRT Implant Improves Outcomes Protocol-driven approach to dietary education and uptitration of neurohormonal blocking medications Mullens W, et al. Am J Cardiol 2011;108:409–415
  24. 24. Exercise Training After CRT Implant Results in Further Improvement Three months after implantation, exercise group had 30 minute supervised sessions 3x per week Patwala AY, et al. J Am Coll Cardiol 2009;53:2332–9
  25. 25. Heart Failure Diagnostics and Remote Monitoring Improve Survival Measures of: •  Pulmonary congestion •  Autonomics •  Patient activity Organization of health care essential to appropriately manage new technology Klersy C, et al. J Am Coll Cardiol 2009;54:1683–94
  26. 26. Echo Optimization of CRT •  Cardiac output is maximized in CRT when LV contraction occurs at the completion of LA contraction Too short… Too long… Just right.
  27. 27. Iterative Method: Allowing Enough Time for Complete Filling of LV
  28. 28. Echocardiographic Optimization of Device Timing Universal echocardiographic device optimization not proven to improve outcomes, however there may be subset of patients that benefit. Ellenbogen, KA et al., Circulation. 2010 Dec 21;122(25):2660-8
  29. 29. Device-Based Optimization of AV and VV Timing •  SMART-AV •  FREEDOM •  ADAPTIVE-CRT Automated, continuous optimization may overcome problems with echo-based techniques Ellenbogen, KA et al., Circulation. 2010 Dec 21;122(25):2660-8; Abraham WT, et al. Heart Rhythm 2010;7:2–3 (abstr) Martin DO, et al. Heart Rhythm 2012;9:1807–1814)
  30. 30. Non-Responder Protocol Chest X-ray Device Interrogation Echo Optimization Advanced Therapies
  31. 31. Conclusions •  Response to CRT is multi-factorial •  Echo 6 month post-implant to assess reverse remodelling •  Optimize medications, diet and exercise •  Echo optimization as part of a “protocol” for CRT non-response