Treatment of AF by Pacing Therapy Is there Anything Else Beyond AVN Ablation?

Transcription

1 1 Treatment of AF by Pacing Therapy Is there Anything Else Beyond AVN Ablation? Chu-Pak Lau, MD Honorary Clinical Professor Queen Mary Hospital The University of Hong Kong

2 How to Prevent AF by Pacing 1. Heart failure increases AF. An appropriate pacing site or rate that improves or reduces left ventricular dysfunction will reduce AF 2. Direct effect of pacing on AF occurrence: 2.1 Homogenization of atrial EP properties 2.2 Prevention of triggers 2.3 Termination of AF precursors 2.4 Autonomic modulation 2

3 Effect of Pacing Site and Pacing Algorithms for AF Harmful VVI RVA DDD with short AVI Potentially Beneficial Site Physiological pacing RVS CRT RA septal/raa RA dual site 3 Algorithm Minimizing RVp acrt AF prevention Ap AT termination Ap

4 4 CVS Outcomes of Pacing Trials (1) Healey JS et al Circulation 2006; 114: AF CVA

5 Mr. TWG M/65 (1) Hx. of HT for 5 yrs Symptomatic PAF and failed 3 antiarrhythmic agents CC- normal coronary, LV gram- LVEF 60% AV nodal ablation and DDDR pacemaker implanted (May 2000) 5

6 Mr. TWG M/65 (2) Developed persistent AF 2 yrs after procedure Progressive worsening of exercise capacity to 2 flights of stairs Echo- Impaired LV function with LVEF 35% and? Apical aneurysm Upgrade to RV septal pacing 6

7 RVA Pacing-Induced CMP RAO View 7 LAO View

8 8 MOST substudy - Effect of % VP Heart Failure Hospitalizations Incidence of AF Sweeney, et. al. Circulation. 2003; 107:

9 Upgrading RVA to RVS Improves LV Performance Tse HF..Lau CP et al. JCE 2009; 20: Pts & Methods : 12pts underwent RVA RVS vs 12pts continuing RVA pacing Conclusion :A significant reversal of harmful effect on LV function after RVA RVS 9

10 Perfusion and Functional Changes of RVA vs RVS Pacing Tse HF Lau CP. JACC 2002;40: Stress Thallium Defect LVEF % Conclusion: RVS pacing preserved long term myocardial perfusion 10

11 Effect of RV Pacing Site on LV Function in CHB: Protect-Pace study Kaye GC et al. EHJ 2015;36: pts (74±11 yrs, 76% males) were randomised to RVA (n=120, XRay-confirmed = 71%) or RVHS (n=120, XRay-confirmed = 69%) and followed up for 2 years LVEF LVEF % Pre Post 58 P<0.05 P< ± ± ± ± RVA RVNA 100% 80% 60% 40% 20% 0% AF Conclusion: LVEF decreased with pacing without difference between sites. AF occurrence were similar % 7.5% Permanent AF RVA 90.0% RVNA 96.0% Median Burden (mins)

12 Meta-analysis of RVA vs RVNA Pacing Shimony A et al. Europace 2012;14: RCT identified involving 754 pts FU > 2m. RVS resulted in better LVEF of 4.27% ( 12m) and 3.71% (<12m) than RVNS pacing. No significant difference if baseline LVEF is normal. 12

13 Limitations of RV Pacing Site Studies 1. Small number of patients 2. Carry over effects in cross-over studies 3. Site of RVS pacing not well defined 4. Duration of follow up 5. Effects variable and more important in 5.1 younger patients who have a long life of pacing, 5.2 extent of dyssynchrony induced (QRS width, Zhang JCE 2008; mechanical, Ahmed HR 2014) 5.3 those with pre-existing structural heart disease (Tops LF, JACC 2009), and 5.4 higher % Vp (Sweeney, Circ 2003) 13

14 Dual-chamber or Ventricular back up pacing in ICD? (DAVID trial) Wilkoff BL et al JAMA 2002; 288: Question to Answer : Does DDD improve ICD efficacy over VVI-ICD? Pts & Methods : 506 pts and EF <40% were randomized to DDDR/VVI ICD s. Vp higher in DDDR (>60%) Conclusion : DDDR-ICD that induced high % RV pacing may be detrimental in ICD recipients without a pacing indication. 14

15 Minimizing Ventricular Pacing to Reduce AF in SND Sweeney MO et al. N Engl J Med 2007; 357: (1) Background : Ventricular de-synchronization may negate the benefit of AV synchrony Pts & Methods : 1065 pts with SND, intact AV conduction, normal QRS interval were randomised to receive DDD (AVI ms) vs DDD with algorithm to allow AAI with DDD backup Results : 4.8% risk reduction for AF (RRR 40%), and a trend for reducing AF interventions. Vp 9.1 vs 99% (p<0.001), AP ~70% (ND) Conclusion : Avoiding RV pacing have benefit to reduce persistent AF in SND pts who do not require Vp 15 15

16 Minimizing Ventricular Pacing to Reduce AF in SND Sweeney MO et al. N Engl J Med 2007; 357: (2) 16 16

17 21 Does CRT reduce AF?

18 CARE-HF : Impact of CRT on Clinical AF Hoppe VC et al Circulation 2006; 114 : (1) Pts & Methods : Pts recruited in the CARE-HF trial were monitored for AF using adverse event reporting and ECG on follow up. Pts with AF detected by device only (93pts or 22%) were not included 22

19 24 LA Volume and AF Reduction in mild HF treated with CRT (MADIT-CRT) Brenyo A et al. JACC 2011;58: Pts and Methods: 1809/1820 pts with MADIT-CRT were stratified by LAV > 20% or less for 1 st outcome of AT/AF LAV Response AF Occurrence

20 25 LV Only Pacing Compared to BVP in CRT Lee KL Lau CP, JCE 2007;18: (1) Synchronization of LV pacing to spontaneous RV conduction may obviate RVP in CRT. Acute hemodynamic study on 17 pts with LVEF 30±1% and QRS 135±25 ms with LVp vs BVp LV Function

21 LV Only Pacing Compared to BVP Lee KL Lau CP, JCE 2007;18: (3) LV 27 RV

22 Adaptive CRT Algorithm AdaptivCRT must be programmed to Adaptive BiV and LV Heart rate 100 bpm, and Intrinsic AV conduction AS-VS 200 ms AP-VS 250 ms + LV Capture confirmed by LVCM* Adaptive LV pacing is suspended if a tachyarrhythmia or incompatible device operation occurs. *If LVCM is programmed off, this condition is removed. Note: AdaptivCRT is available in the DDD and DDDR pacing modes. 28

23 AdaptivCRT AF Analysis 1 AdaptivCRT Reduced AF Risk by 46% 1 Martin D, Lemke B, Aonuma K, et al. Clinical Outcomes with Adaptive Cardiac Resynchronization Therapy: Longterm Outcomes of the Adaptive CRT Trial. HFSA Late Breakers. September 23,

24 Mechanisms of Atrial Pacing Prevention of AF 1. Prevention of pause dependent AF 2. Suppression of APB or PV triggers 3. Induce conduction block of APB 4. Prevent abrupt change in atrial cycle length (short-long sequence) 5. reentry by pre-excitation 30

25 Considerations for Pacing Trials for AF Prevention Patients Primary/ Secondary Pacing indications Design RCT/crossover Length of follow up Adequate power Device Types of algorithm Site of atrial lead %Vp Endpoints CVS outcome Clinical AF: - -symptomatic -asymptomatic Device detected AF: -duration -burden -rate A pacing trial for AF should test the effect of rate (algorithm) and site of pacing in a clearly defined population, preferably using RCT with adequate power and length of FU, minimizing Vp and assessing clinical endpoints 32

26 Atrial Prevention Pacing on AF Burden: (SAFARI) Trial (1) Gold MR et al. Heart Rhythm 2009; 6: Pts & Methods: 240/555 pts with prior clinical AF had device recorded AF at 4 months after receiving Vitatron Selection They were randomised to PPTs or standard pacing. Study Characteristics: Patients Secondary prevention Pacing indicated pts Class I (72%), II (28%) HF Design RCT Single blinded Parallel group High vs Low burden ( 6%) 6 months follow up 33 Device Vitatron PPTs Lead site not specified Endpoints 1 : AF Burden 1 : Risk of permanent AF

27 Atrial Prevention Pacing on AF Burden: (SAFARI) Trial (2) Gold MR et al. Heart Rhythm 2009; 6: AF Burden after PPTs Conclusion PPTs reduced AF burden by 0.08h/day (p=0.03), without difference in permanent AF. There was 96% Ap and increase of 11.6% Vp in the on vs 1.9% in off group compared to baseline 34

28 Atrial Overdrive Pacing to Prevent New Onset AF (1) Hohnloser SH Lau CP ASSERT Investigator. HR 2012;9: Pts & Methods: 2343 pts 65yr with HT received pacemaker/icd, and followed up for 2.5 years, with overdrive pacing on or off. Study Characteristics: Patients Design Device Endpoints Primary prevention HT, device indicated SND (34%), AVB (57%), Both (13%) RCT Single blind Parallel group 2.5 yrs SJM, AFx RAA (86%) Septal (4%) Others (10%) 1 : ECG documented AF (Symptomatic or asymptomatic ) 35

29 Atrial Overdrive Pacing to Prevent New Onset AF (2) Hohnloser SH Lau CP ASSERT Investigator. HR 2012;9: Time to First AF: P=NS Conclusion: 60pts with AFx on (1.96%/yr) had AF vs 45 pts (1.44%/yr) in AFx off (p=0.1). No differences in MACE. AFx was associated with more crossover, false positive device AF detection and earlier battery depletion 36

30 39 Ismer B, 2004

31 LAS vs RAA on Atrial Mechanical function and Dyssynchrony Wang M Lau CP, Tse HF. Europace 2011;13: (1) 40 Pts and Methods: 30 pts with SND and PAF paced in LAS or RAA were examined with tissue Doppler for atrial function and dyssynchrony Results: LAS pacing increased LAEF (52 ± 16 vs 39 ± 14%, p<0.029), and shortened interatrial dyssynchrony

32 Bachmann s Bundle Pacing Bailin S et al JCE 2001; 12: pts (70 ± 11 yrs) received RAA or BB pacing Endpoint : chronic AF. Not on AAD 42

33 Prospective Study to Assess Site and Rate of Atrial Pacing: Septal Pacing for AF Suppression Evaluation (SAFE) Lau CP Tse HF et al for the SAFE Investigators. Circulation 2013;128: (1) Pts & Methods: 385 patients with documented clinical AF was followed for the development of persistent AF after > 3.1 years, assessing RAA vs LAS, and with and without atrial overdrive pacing. Power 80% to detect 30% difference. AVI programmed to avoid RVp Patients Design Device Endpoints Secondary prevention Pacing indication RCT Single blinded 4 parallel groups At least 2 yrs Power 80% for Δ 30% AF SJM, AFx RAA or LAS 1 Persistent AF 2 AHRE AF Burden QoL 43

34 Prospective Study to Assess Site and Rate of Atrial Pacing: Septal Pacing for AF Suppression Evaluation (SAFE) Lau CP Tse HF et al for the SAFE Investigators. Circulation 2013;128: (2) 44

35 Prospective Study to Assess Site and Rate of Atrial Pacing: Septal Pacing for AF Suppression Evaluation (SAFE) Lau CP Tse HF et al for the SAFE Investigators. Circulation 2013;128: (3) 45 Conclusion: LAS pacing reduced PWD (97 vs 129 ms), and Ap was increased from 56 to 92% with overdrive pacing without increasing Vp (26%). There was no difference in outcome of rate/site on persistent AF nor AF burden.

36 Prospective Study to Assess Site and Rate of Atrial Pacing: Septal Pacing for AF Suppression Evaluation (SAFE) Lau CP Tse HF et al for the SAFE Investigators. Circulation 2013;128: (4) 46

37 APP + ATP with Minimising Ventricular Pacing Reduced Chronic AF Padeletti L et al. MINERVA multi-center trial. HR 2015 in press (1) Pts and Methods: Patients with prior PAF were randomized to either DDDR (n=385), MVP (n=398) or DDDRP + MVP (n=383) for the incidence of chronic (persistent/permanent) AF Patients Design Device Endpoints Secondary prevention Pacing indication (no CHB) RCT Single blinded 3 parallel groups 2 yrs Medtronic RAA APP ATP MVP 1 chronic AF (permanent or persistent) 2 ATP efficacy and chronic AF 47

38 APP + ATP with Minimising Ventricular Pacing Reduced Chronic AF Padeletti L et al. MINERVA multi-center trial. HR 2015 in press (2) Results: Chronic AF was reduced from 26% in DDDR to 25% in MVP and 15% DDDRP + MVP (p<0.002). Reduction maximum in pts in whom reactive ATP was particularly effective (>44.4% time). Predictors: - long atrial TCL, regular AT rhythm and shorter episodes 48 Conclusion: APP + ATP with MVP reduced progression to chronic AF

39 Conclusion (1) Ventricular Pacing 1. There is little data of the effect of RV pacing sites on the incidence of AF. On the other hand, unnecessary RV pacing may increase AF in pts with bradycardia (or in CRT) 2. CRT may have a beneficial effect on AF 49

40 Conclusion (2) 1. Site of atrial pacing: Atrial Pacing No systematic difference between RAA or septal site on persistent AF. 2. Rate of atrial pacing Atrial overdrive pacing has a neutral effect, but may be harmful if Vp is increased. Atrial Antitachycardia pacing without increasing ventricular pacing may be potentially beneficial. 50

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