1. Mode selection in pacemaker – Evidence review
Dr. Shreetal Rajan Nair
SR, Department of Cardiology

2. Introduction Aims of pacing
Try to normalize cardiac output – heart rate and myocardial contractility
Achieve chronotropic competence, AV and interventricular synchrony
- Bring comorbidities associated with pacing to a minimum
- Improve exercise tolerance and quality of life.

3. What are the options available ?
Single chamber – atrial , ventricular
Dual chamber
Fixed rate vs rate adaptive
Physiologic pacing ?
Includes atrial as well as dual chamber pacing

4. Indications SND A V conduction block Other indications
- Neurocardiogenic syncope
- Carotid Hypersensitivity Syndrome
- HCM
- Long QTS

5. Pacing in SND SND is the most common indication for pacing.
Patients with SND prone to develop AF and AV block
AV block in SND
- 20% at the time of diagnosis
% in pacemaker implanted patients during 5 year follow up
AF in SND
- 40 – 70% at the time of diagnosis
– 22.3% during follow up
in pacemaker implanted patients incidence of AF influenced by pacing mode, duration of ventricular pacing and follow up duration

6. Pacing modes in SND Single chamber –AAI vs VVI
Single vs dual - VVI vs DDD

7. Evidence review Major randomized trials Danish study – SSS
PASE (Pacemaker Selection in the Elderly) – SSS + AVB
MOST (Mode Selection Trial ) - SSS
CTOPP (Canadian Trial of Physiologic Pacing ) - SSS + AVB
DANPACE (The Danish Multicenter Randomized Study on Atrial Inhibited Versus Dual-Chamber Pacing in Sick Sinus Syndrome)– SSS
UKPACE (United Kingdom Pacing and Cardiovascular Events)- AVB

8. HRS/ACCF expert consensus statement on pacemaker device and mode selection. J Am Coll Cardiol 2012;60:682–703

9. HRS/ACCF expert consensus statement on pacemaker device and mode selection. J Am CollCardiol 2012;60:682–703

10. Endpoints studied All cause mortality AF Stroke Heart failure
Quality of life
Pacemaker syndrome

11. AF
Significant decrease in AF incidence in Danish, CTOPP and MOST with relative risk reduction of 46%, 18% and 21% respectively.
Supported dual chamber and atrial pacing

12. Stroke or thromboembolism
Danish study showed a 57% risk reduction with atrial based pacing
Metaanalysis also showed a trend in favour of atrial based and dual chamber pacing modes
This effect may be due to less incidence of AF as already described

13. Heart failure
Danish study : atrial pacing improved heart failure status
MOST : 10% in DDDR group vs 12.3% in VVIR group
Other studies failed to show a benefit for atrial based pacing

14. Quality of life and functional status
CTOPP : overall there was no significant effect of pacing mode on quality of life
subgroup analysis showed improved quality of life in those with high degree of pacing
MOST and PASE showed definite benefit of dual chamber pacing on quality of life

15. Pacemaker syndrome
Symptoms of PACEMAKER SYNDROME was found to be more in ventricular only pacing vs DDDR or AAIR
improvement in quality of life reported earlier believed to be lower incidence of pacemaker syndrome

16. Overall mortality
Only the Danish study showed a benefit in favour of atrial based and dual chamber pacing
Other studies and metaanalysis failed to prove any definite advantage for atrial or dual chamber pacing.

17. The effect of RV pacing
RV pacing associated with RV dysfunction and interventricular dyssynchrony due to abnormal non physiologic activation sequence.
DDDR pacing associated with more dyssynchrony and decrease in EF when compared with AAIR pacing
MOST : increased incidence of HF and AF in DDDR vs AAIR

18. Effect of RV pacing
When compared with normal LV function vs LV dysfunction , those with normal LV function fared better.
Factors influencing patient outcomes :
LV function
Degree of RV pacing
Presence of structural heart disease

20. Managed ventricular pacing (MVP)
Long-term RV pacing causes a deterioration of LV function through complex effects on regional ventricular wall strain and loading conditions
MVP searches for intrinsic conduction and avoid unnecessary ventricular pacing
Pacemakers can switch pacing mode from AAI(R) to DDD(R) in the Managed Ventricular Pacing (MVP) mode
The MVP mode provides functional AAI(R) pacing with the safety of dual-chamber ventricular support in the presence of transient or persistent loss of conduction
The criterion to switch to backup ventricular pacing is loss of AV conduction for two of the last four pacing cycles (the four most recent A-A intervals

21. SAVE – PACe trial

23. Results
Minimal Vpacing algorithms showed decrease in AF burden and progression to permanent AF.

24. Single chamber atrial pacing vs dual chamber pacing
DANPACE: DDDR better in SND than AAIR only pacing - this finding was in contrary to the earlier studies – explanation was minimal ventricular pacing protocols were used in the DDDR group in DANPACE.
Very short and very prolonged AV intervals : increased AF burden on follow up.
DANPACE used moderately prolonged AV interval protocols which resulted in less AF burden

25. Single chamber ventricular pacing vs dual chamber pacing
No trial showed any significant benefit of dual over ventricular pacing
Back up VVI pacing preferred in those not requiring frequent pacing
VVI pacing preferred in those with permanent and long standing persistent AF

26. Rate adaptive pacing
Indicated only for symptomatic chronotropic incompetence
No significant effect on quality of life or exercise time though peak exercise heart rate increased
Increased frequency of heart failure, AF noted in dual chamber rate adaptive pacing vs those without

27. Circulation 2006;114:11-17

28. Circulation 2006;114:11-17

29. Endpoint assessment – all cause mortality
Healey et al Randomized Trials of Pacing Mode: A Meta-Analysis; Circulation. 2006;114:11-17
All cause mortality

30. Endpoint assessment – AF
Healey et al Randomized Trials of Pacing Mode: A Meta-Analysis; Circulation. 2006;114:11-17
AF incidence

31. Endpoint assessment – STROKE
Healey et al Randomized Trials of Pacing Mode: A Meta-Analysis; Circulation. 2006;114:11-17

32. Pacing and mode selection in SND

33. AV BLOCK

34. AV conduction disease
Intermittent AV conduction abnormalities progress to complete heart block on long term follow up
The minimum requirement is to prevent symptomatic bradycardia
The aim of pacing to establish AV synchrony without affecting ventricular synchrony
If there is no sinus node dysfunction then VDD mode will maintain AV synchrony and chronotropic competence

35. Why AV synchrony is essential
Positive effect on cardiac output
Increases stroke volume by 50% and decrease LAP by 25%
AV synchrony also helpful in diastolic dysfunction

36. Three randomized trials
PASE
UKPACE
CTOPP
compared single vs dual chamber pacing in AV conduction disease

37. 3 randomized trials Mostly elderly ( 73-80 yrs )
CTOPP and PASE had both patients with sinus node and AV conduction disease.
AV block as primary indication of pacing : 49% in PASE and 51% in CTOPP
UK PACE had patients with AV conduction disease only

38. UKPACE 2005 - NEJM multicenter, randomized, parallel-group trial
2021 patients ; 70 years of age or older
high-grade atrioventricular block
randomly assigned to receive a single-chamber ventricular pacemaker (1009 patients) or a dual-chamber pacemaker (1012 patients).
In the single-chamber group, patients were randomly assigned to receive either fixed-rate pacing (504 patients) or rate-adaptive pacing (505 patients).
The primary outcome was death from all causes.
Secondary outcomes included atrial fibrillation, heart failure and a composite of stroke, transient ischemic attack or other thromboembolism

39. RESULTS
The median follow-up period was 4.6 years for mortality and 3 years for other cardiovascular events.
The mean annual mortality rate was 7.2 percent in the single-chamber group and 7.4 percent in the dual-chamber group (hazard ratio, 0.96; 95 percent confidence interval, 0.83 to 1.11).
no significant differences between single-chamber pacing and dual-chamber pacing in the rates of atrial fibrillation, heart failure or a composite of stroke, transient ischemic attack or thromboembolism.

43. CONCLUSION
In elderly patients with high-grade atrioventricular block, the pacing mode does not influence the rate of death from all causes during the first five years or the incidence of cardiovascular events during the first three years after implantation of a pacemaker.

45. DANPACE Nielsen JC, et al. Eur Heart J 2011;Feb 7:[Epub]
Trial design: Patients with sick sinus syndrome were randomized to single-lead atrial (AAIR) pacing (n = 707) vs. dual-chamber (DDDR) pacing with an atrioventricular interval of ≤220 msec (n = 708). Mean follow-up was 5.4 years.
Results
(p = NS)
Pacing in the atrium: 58% in the AAIR group and 59% in the DDDR group; pacing in the ventricle: 65% in the DDDR group
Survival: similar between groups (29.6% vs. 27.3%, p = 0.53)
Paroxsymal atrial fibrillation ↑ with single-lead atrial pacing (28.4% vs. 23.0%, p = 0.024)
Need for reoperation: ↑ with single-lead atrial pacing (22.1% vs. 11.9%, p < 0.001) 59 58 %
Conclusions
Among patients with sick sinus syndrome, dual-chamber pacing appears to be superior to single-lead atrial pacing
Dual-chamber pacing resulted in reduced frequency of atrial fibrillation and need for reoperation
Pacing in the atrium
AAIR
DDDR
Nielsen JC, et al. Eur Heart J 2011;Feb 7:[Epub]

46. Effects of pacing modes on various parameters

47. AF
Those with AV block indication for pacing were less likely to progress to permanent AF when compared to SND indication for pacing – CTOPP trial
UKPACE – annual event rates for developing AF were similar in both dual and single chamber groups

48. Stroke , mortality and heart failure
No difference between dual chamber or single chamber pacing in the above parameters

49. Exercise capacity and quality of life
CTOPP and some short term crossover studies showed increased exercise tolerance and improved quality of life by patient symptom scores with dual chamber rate adaptive pacing when compared to fixed rate ventricular pacing ( but statistical significance not attained)

50. Effect of rate adaptive pacing

51. Pacemaker syndrome PASE
- 26% of patients randomized to VVI mode had severe symptoms attributable to pacemaker syndrome
– 50% of patients who were programmed to DDD from VVI mode had AV block
Whereas only 7% of patients in CTOPP needed a pacemaker revision over a 6 yr follow up period

52. Pacing mode after AV junction ablation
Single chamber pacing is the preferred mode of therapy for patients who have AV junction ablation for medically refractory AF

53. Potential deleterious effects of ventricular pacing
No randomized trials available
Algorithms to minimize ventricular pacing have not found to be useful in patients with AV block.
Some case reports have even reported to have deleterious effects

54. VDD pacemaker in AV block
Single lead , dual chamber
Decreases procedure time and costs
Restore AV synchrony
Atrial lead will be a floating bipole and its sensing function may degrade over time needing revision
Useful in young patients with CCHB

57. HYPERSENSITIVE CAROTID SINUS SYNDROME

58. Evidence
No large randomized clinical trials of pacing mode have been conducted in this syndrome.
AAI pacing alone has been shown to be ineffective in this syndrome due to concomitant AV block during carotid sinus activation
Morley CA, et al. Carotid sinus syncope treated by pacing. Analysis of persistent symptoms and role of atrioventricular sequential pacing. Br Heart J 1982;47:411– 8
There is a potential benefit of dual-chamber pacing to minimize the impact of the vasodepressor response and prevent pacemaker syndrome.

59. Evidence
In a prospective randomized study of pacing vs. no pacing therapy performed in 60 patients with carotid sinus syndrome, syncope recurred in 16 (57%) of the no-pacing group and in only 3 (9%) of the pacing group (p0.0002)
18 of 32 (56%) of the paced group received VVI devices and the remainder received DDD devices
Brignole M, et al. Long-term outcome of paced and nonpaced patients
with severe carotid sinus syndrome. Am J Cardiol 1992;69:1039 – 43

60. Evidence
comparisons made between VVI vs. DDDR vs. DDDR with rate drop response in patients with carotid sinus syndrome without evidence of concomitant SND or AV block.
The primary endpoints of syncope or presyncope were significantly reduced after pacemaker implantation in all three groups
no significant differences in the primary outcomes were demonstrated among the three pacing modalities.
minor benefits of DDDR pacing was noted vs. baseline in the categories but no pacing mode was found to be superior.
Despite the physiological hemodynamic advantage of AV synchrony, the superiority of DDD pacing was not observed in this study
McLeod CJ, Trusty JM, Jenkins SM. Rea RF, Cha Y-M, Espinosa RA.Friedman PA, Hayes DL, Shen W-K. Method of pacing does not affect the recurrence of syncope in carotid sinus syndrome. Pacing Clin Electrcrossover study

61. NEUROCARDIOGENIC SYNCOPE

62. Trial evidence

63. Neurocardiogenic syncope
role of permanent cardiac pacing for neurocardiogenic syncope remains controversial
The Vasovagal Pacemaker Study II (VPS 2) reported no significant reduction in the time to a first recurrence of syncope during dual-chamber pacing over 6 months of follow-up
The Vasovagal Syncope and Pacing Trial (SYNPACE) also reported that there was no significant difference between comparison groups
The subgroup of patients who had demonstrated asystole during tilt-table testing had a significant increase in time to first syncope recurrence compared with those with bradycardia alone (91 vs 11 days, respectively)

64. PACING IN NEUROCARDIOGENIC SYNCOPE
The ISSUE II trial reported that permanent pacing in patients with periods of asystole resulted in a significant reduction in the frequency of syncope.
In the Syncope and Falls in the Elderly Pacing and Carotid Sinus Evaluation (SAFE PACE) study, permanent pacing reduced falls, recurrent syncope and injuries in elderly patients with frequent nonaccidental falls and cardioinhibitory carotid sinus hypersensitivity.

65. Hypertrophic cardiomyopathy

66. M – PATHY trial 48 patients Randomized Double blind cross over study
DDD pacing vs AAI pacing
Though outflow tract gradient decreased with dual chamber pacing no much significance was found in the quality of life between the two groups.

67. Long QT syndrome

68. Long QT syndrome No randomized trials available
Indicated in pause dependent VT
AAI vs DDD vs VVI – direct comparisons not available
Dual chamber pacing better than single chamber pacing

69. Complications – evidence review

70. Summary
Compared with ventricular pacing, the use of atrial-based pacing does not improve survival or reduce heart failure or cardiovascular death.
Atrial-based pacing reduces the incidence of atrial fibrillation and may modestly reduce stroke

71. Thank you