Device based CRT optimization: is there a future? Lessons learned from published trials

Transcription

1 Device based CRT optimization: is there a future? Lessons learned from published trials C. Leclercq Department of Cardiology Centre Cardio-Pneumologique Rennes, France

2 Presenter Disclosure Information Christophe Leclercq, MD, PhD FINANCIAL DISCLOSURE: Research Grants: Boston Scientific, Medtronic, Sorin Group, St. Jude Medical, Consulting / Advisory board: Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group Lectures: Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, GE Stock Options: None; Salary Support: None; Speaker Bureau: None

3 Optimization of CRT? Optimization of basic and simple parameters of pacing (rate responsive algorithm, UTR ) Optimization of AV and VV timings Optimization of medical treatment (Drugs and doses)

4 Rationale of CRT CRT is based on permanent and complete biventricular capture 1296 patients Endpoints: mortality and HF Quartiles of % of Biv pacing (0-92%, 93-97%, 98-99%, 100%) Koplan. J Am Coll Cardiol ;355-60

5 Importance of Biv pacing Koplan. J Am Coll Cardiol ;355-60

6 Why do we need to optimize AV and VV timings? There is no a single dyssynchrony pattern in CRT patients Normal versus long PR interval patients Interatrial conduction delay Different patterns of ventricular conduction disorders Different magnitude of LV dysfunction Different extent of LV dyssynchrony Different underlying cardiomyopathies (ischemic versus non ischemic) Impact of medical treatment on cardiac conduction

7 Why do we need to optimize AV and VV timings? Because all the devices allow AV and VV optimization Because it s not politically correct to let a patient without delays optimization Because inappropriate cardiac timings may enhance hemodynamic deterioration Because AV and VV delays optimization may improve the patient s outcome and thus might increase the rate of responders.

8 Rational for AV delay optimization Causes of non responde to CRT Mullens. J Am Coll Cardiol 2009; 53:

9 Improvement with intervention Mullens. J Am Coll Cardiol 2009; 53:

10 Impact of AV delay and VV timing optimization on patient s outcome Abraham, HFSA 2007

11 Should AV Delays be optimized? 80% MIRACLE Study % of Patients 60% 40% 20% 0% < >120 Optimal AV Delay Predis N=353 3 Mo N=288 6 Mo N=182

12 Optimization of AV delay in RCTs CONTAK CD trial : no optimization CARE-HF, MIRACLE and REVERSE: echocardiographic transmitral flow MADIT CRT: latest approved optimization techniques COMPANION: electrical algorithm No prespecified comparison

13 Device-based algorithms Intracardiac based electrograms Quick-opt Bakker. J Cardiovasc Electrophysiol ;

14 FREEDOM Trial Prospective, randomized, double-blinded, multicenter study Enrollment 2 weeks post CRT-D implant 1:1 Randomization stratified by cardiomyopathy classification Treatment Group QuickOpt Control Group Standard of care AV/PV Optimization VV Optimization Empiric programming or One-time non-iegm optimization within first 4 weeks Follow-up (3,6, 9, 12 months) QuickOpt optimization Follow-up (3, 6, 9, 12 months)

15 FREEDOM Trial Primary Endpoint Heart failure clinical composite score (CCS) as defined by Packer 1 Secondary Endpoints All-cause, cardiovascular and heart failure mortality All-cause, cardiovascular and heart failure hospitalization Abraham HRS 2010

16 FREEDOM Trial Results: Primary Endpoint HF Clinical 1644 pts with CRT indication (80% ICD, 60% ischemic) Treatment Control ECHO and other Optimization Methods Empiric Programming/Not Optimized HF CCS n % n % n % Improved % % % Unchanged % % % Worsened % % % Total % % % No difference for NYHA class, QOL, 6 MWT and reverse remodeling

17 Device-based algorithms Intracardiac based electrograms Expert Ease for Heart Failure Gold. J Cardiovasc Electrophysiol ;490-6

18 The SMART AV trial 3 arms: Fixed AV delay (120 ms), Echo (iterative method) and the smart delay algorithm; 980 patients randomized Primary endpoint: absolute pairwise changes in LVESV between baseline and 6 months evaluated in a core laboratory Sample size calculation: difference of 15 ml between fixed nominal and optimized groups (echo-optimized or SD) and no difference between SD and echo-optimized groups (a: 0.05 and power 80%) The value of 15 ml was based on the assumption that 50% of the decrease in LVESV in RCTs (median value 30 ml) was related to AV optimization SD: Automatic IEGM- based 1) Intrinsic AV intervals Sensed (As-Vs) and paced (Ap-Vs) 2) Interventricular timing RVs-LVs interval 3) LV lead location (implanting physician)

19 SMART-AV Study Design Enrollment and Implant CRT-D with SmartDelay Program device to VVI-40-RV Post-Implant Visit (1 to 14 days post-implant) (1:1:1 Randomization, Programmed to DDD(R)60) SmartDelay Echo (Iterative) Fixed (120/0) 3- month Visit 3- month Visit 3- month Visit 6- month Visit 6- month Visit 6- month Visit Stein KM, et al. Pacing Clin Electrophysiol. 2010;33(1):54-63

20 The SMART AV trial (Results) No difference between the 3 groups for: The primary endpoint (LVESV) The secondary endpoints LVEDV LVEF NYHA class 6 MWT QOL Ellenbogen Circulation ;122(25):2660-8

21 A wide range of AV delays?? Ellenbogen Circulation ;122(25):2660-8

22 VV timing optimization

23 VV timing Optimization Theoretically attractive to optimize the correction of LV dyssynchrony 35% # # 30% * * mean LVEF (%) 25% 20% 15% 10% 5% 0% Rosanio Sogaard Van Gelder. Am J Cardiol ; Baseline with AV OPT VV OPT Sogaard. Circulation ; Rosanio Circulation. 2003;108:IV-345

24 Randomized trials on VV optimization RYHTHM II ICD 121 patients to simultaneous vs echo-optimized sequential pacing (VTI method) No difference at 6 months of QOL, NYHA or 6MHWT Boriani, Am Heart J 2006;151: DECREASE-HF 306 patients randomized to LV,simultaneous, or sequential pacing (IEGM method, median offset= LV- 50ms) optimal VV=0.333 (RV-LV electrical delay)-20 ms* No advantage of sequential pacing in terms of LV volumes or LVEF Rao, Circulation 2007;115:

25 Conclusions Do not forget to optimize basic pacing parameters and medical treatment No evidence that AV (and VV) delays optimization using echocardiographic techniques or IEGM-based techniques improves the outcome of CRT patients in the overall CRT population. No benefit for AV optimization? Methods not adequate?

26 Do we have to give up? Hemodynamic methods? Continuous optimization (rest and exercise) Response rate (%) 100% 80% 60% 40% 20% 0% Clinical response rate to CRT (composite criterion*)? 86% SonR group (n=57) 62% Control group (n=99)