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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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

SAVE – PACe trial

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

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

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

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

Circulation 2006;114:11-17

Circulation 2006;114:11-17

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

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

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

Pacing and mode selection in SND

AV BLOCK

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

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

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

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

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

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.

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.

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]

Effects of pacing modes on various parameters

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

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

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)

Effect of rate adaptive pacing

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

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

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

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

HYPERSENSITIVE CAROTID SINUS SYNDROME

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.

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

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

NEUROCARDIOGENIC SYNCOPE

Trial evidence

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)

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.

Hypertrophic cardiomyopathy

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.

Long QT syndrome

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

Complications – evidence review

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

Thank you