Mode selection in pacemaker – Evidence review

1. Mode selection in pacemaker– Evidence review Dr. ShreetalRajan 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 - 3- 35% in pacemaker implanted patients during 5 year follow up • AF in SND - 40 – 70% at the time of diagnosis - 3.9 – 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 CollCardiol2012;60:682–703

9. HRS/ACCF expert consensus statement on pacemaker device and mode selection. J Am CollCardiol2012;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 interventriculardyssynchrony 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 vsthose 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

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

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 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) Paroxsymalatrial 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) 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) 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