Permanent HBP vs Septal vs RVP: What evidence do we have

18-01-2020

Raja Selvaraj, JIPMER

Introduction

Formulating the question - Hypothetical patient

60 year old male with syncope
Complete heart block
Normal Echo
DDD pacemaker implant

Question we want to answer

Best way to pace this patient ?
RV apical pacing
RV septal pacing
His bundle pacing
Others

Disclosure

My direct experience with HB pacing is small
Govt funded, academic institute
New drugs and therapies trickle in slowly
Which is often not a bad thing
- Seven year rule
- Some distance to look at it objectively

Health Research Group Most evidence for FDA approval concerns proof of benefit Underpowered to identify risks Initially recommended 5 years after FDA approval Increased to 7 years

RV apical pacing

RV apical pacing

Easiest time tested Needs no special hardware

RV apical pacing - Harmful ?

Difficulty in proving superiority of DDD over VVI pacing in patients with normal LV was clue that RV pacing itself may be harmful even in these patients

primary outcome was death / non fatal stroke no difference in HFH

Mode Selection Trial - Analysis

This is established by seeing that cumulative pacing burden is strongly associated with risk of HFH In DDDR and VVIR modes, percentage cumulative pacing is strongly associated with risk of HFH Similar results for AF

Pacing induced cardiomyopathy

Retrospective analysis of 1750 patients
Defined as > 10% decrease in EF leading to EF < 50%, ruling out other causes
Close to 20 % at 10 yrs
Pacing threshold usually considered 40%, but picm significant even with 20%

Khurshid, … Marchlinski, Francis … Incidence and Predictors of Right Ventricular Pacing-Induced Cardiomyopathy. Heart Rhythm 2014;11:1619-1625

Predictors of PICM

Male sex
Baseline QRS duration
Baseline LV function
Percent pacing
Site of pacing ?

First three are non-modifiable

Percent pacing is modifiable in certain patients, not in this patient

Baseline LV function - Block HF suggests biventricular pacing in patients with reduced EF

RV septal pacing

Theoretical benefits

Better synchrony
Narrower QRS
Conduction system capture in some ?

Summary of evidence

Metaanalysis (1) - Better LV function with septal pacing
PROTECT-PACE (2) - Randomized, prospective, multi-center - No clear benefit after two years

Shimony A, Eisenberg MJ, Filion KB, Amit G. Beneficial effects of right ventricular non-apical vs. apical pacing: a systematic review and meta-analysis of randomized-controlled trials. Europace. 2012;14(1):81–91.
Kaye GC, Linker NJ, Marwick TH, et al. Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study. Eur Heart J. 2015;36(14):856–862.

PROTECT-PACE

RCT, 240 patients
RV apex or RV high septum
2 years FU
Decrease in LVEF in both, no difference
No difference in mortality, HFH or AF

Biventricular pacing

Biventricular pacing ?

Block HF - Patients with AV block and EF < 50%, BiV pacing better
BIOPACE - BiV pacing not better then RV pacing in patients with AV block

HB pacing

Permanent His bundle pacing

First described in 2000 (1)
Picked up momentum within last 10 years

Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation. 2000;101(8):869–877

Theoretical benefit

Best way to provide synchrony

By design, HB pacing is the best form of multifocal pacing utilising the intrinsic conduction system to pace the ventricles in synchronous fashion

Issues

Success rate around 75%
Longer procedural and fluoroscopy times
High threshold (> 2.5 V at 1 ms) in 10%
Increase in threshold by > 1V in 10%
Battery longevity
Sensing issues
Late development of infra-hisian block ?

Issues - Success rate

Around 80-90% in experienced centers
75% more realistic (1)
Success rate varies with substrate

Bhatt, A. G. et al. The efficacy of His bundle pacing: lessons learned from implementation for the first time at an experienced electrophysiology center. JACC Clin.Electrophysiol. 4, 1397–1406 (2018).

Issues - Capture thresholds

On average, higher than RV pacing
At 2 years, threshold > 2.5 in 14%
Lead revision required in 4.2 % (1)

Higher threshold to begin with and increase in threshold in a proportion of patients This is a function of the anatomy of the region and may not be something that can be altered

Abdelrahman, M. et al. Clinical outcomes of his bundle pacing compared to right ventricular pacing. J. Am. Coll. Cardiol. 71, 2319–2330 (2018).

Real world single center experience

101 implants at a single center (Valley Hospital, NJ)
75% acute success
56% in patients with CHB
Early or late threshold rise in 32%
Lead revision in 8%

Bhatt, A. G. et al. The efficacy of His bundle pacing: lessons learned from implementation for the first time at an experienced electrophysiology center. JACC Clin.Electrophysiol. 4, 1397–1406 (2018).

High pacing threshold - Cascading effects

Need for lead revision
More pulse generator replacements
- Cost (added to higher initial cost)
- Risk of complications during each replacement procedure

Evidence - Prospective crossover trials

Ochetta 2006 - 6 mths 18 pts Improved NYHA, 6MWT, QOL, hemodynamics (1)
Kronberg 2014 - 24 mths, 38 pts, Improvement in EF, no improvement in functional class (2)
Pastore 2014 - 37 pts, better LV synchrony, better LA function (3)
Catanzanti 2014 - 26 pts, 36 mths. improved indices of ventricular function (4)

Crossover designs good to measure physiological differences, QOL differences Not good for long term outcomes which are more important

E. Occhetta et al. Prevention of ventricular desynchronization by permanent para-Hisian pacing after atrioventricular node ablation in chronic atrial fibrillation: a crossover, blinded, randomized study versus apical right ventricular pacing. J Am Coll Cardiol, 47 (2006), pp. 1938-1945
M.B. Kronborg et al. His or para-His pacing preserves left ventricular function in AV block: a double-blind, randomized, crossover study. Europace, 16 (2014), pp. 1189-1196
G. Pastore et al. Hisian area and right ventricular apical pacing differently affect left atrial function: an intra-patients evaluation. Europace, 16 (2014), pp. 1033-1039
Catanzariti D et al. Permanent His‐bundle pacing maintains long‐term ventricular synchrony and left ventricular performance, unlike conventional right ventricular apical pacing. Europace. 2012; 15:546–553

Evidence - Retrospective comparison

Pastore 2016. 12 mths FU, 148 HBP. Lower risk of AF progression
Vijayaraman 2018. Observational, case control. 5 yrs, endpoint - hfh + mortality reduced, less pacing induced cmp, no ef reduction
Abdelrahman 2018. Observational cohort, 332 hbp, 432 rvp, reduced primary endpoint - mortality + HFH

Two studies from the Geisinger health system provide the bulk of evidence in ref 2, 2011 implants, smaller number, longer FU in ref 3, 2013-2016 implants, larger number, more recent data, shorter FU

Pastore, G. et al. The risk of atrial fibrillation during right ventricular pacing. Europace 18, 353–358 (2016).
P. Vijayaraman, A. Naperkowski, F.A. Subzposh, et al. Permanent His bundle pacing: Long-term lead performance and clinical outcomes. Heart Rhythm, 15 (2018), pp. 696-702
M. Abdelrahman, F.A. Subzposh, D. Beer, et al. Clinical outcomes of His bundle pacing compared to right ventricular pacing: Results from the HBP registry. J Am Coll Cardiol, 71 (2018), pp. 2319-2330

Pastore 2016

477 patients HA, RVS, and RVA in 148, 140, and 189 patients, respectively. Follow up around 60 mths

Pastore, G. et al. The risk of atrial fibrillation during right ventricular pacing. Europace 18, 353–358 (2016).

Vijayaraman 2018

94 pts with HBP (80% success) vs 98 pts with RVP (RVA 60, RVS 38)
Decline in LVEF in RVP group
Less pacing induced CMP (2% vs 22%)

Earlier experience, smaller number, more follow up

P. Vijayaraman, A. Naperkowski, F.A. Subzposh, et al. Permanent His bundle pacing: Long-term lead performance and clinical outcomes. Heart Rhythm, 15 (2018), pp. 696-702

Abdelrahman 2018

Implants from 2013-2016
newer experience, larger data, less follow up
Successful HBP in 92%
Endpoint - composite of death, HFH, BiV upgrade - 25% vs 32%
Trend towards lower mortality (17.2 vs 21.4)

M. Abdelrahman, F.A. Subzposh, D. Beer, et al. Clinical outcomes of His bundle pacing compared to right ventricular pacing: Results from the HBP registry. J Am Coll Cardiol, 71 (2018), pp. 2319-2330

Summary

Summary

Is RVS pacing better than RVA pacing - Maybe (small)
Does RVS pacing have downsides - No
Is HB pacing feasible ? - Yes (not in all)
Does HB pacing result in better outcomes ? - Maybe
Does HB pacing have downsides ? - Yes
Do the benefits outweigh the downsides ? - Dont know
Is LB area pacing a better option ? - Dont know
Is this the final word ? - No

What do the guidelines say?

2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society

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Permanent HBP vs Septal vs RVP: What evidence do we have 18-01-2020 Raja Selvaraj, JIPMER