The importance of avoiding unnecessary right ventricular pacing in clinical practice

Table 1 Summary of the major pacing and implantable cardioverter-defibrillator randomized trials that compared atrial (AAI or DDD) vs ventricular based pacing strategies

Ref.	Patients	Follow-up	Pacing/ICD	Study groups	Endpoints	Results
	(n)	(yr)	indication
Danish study[8] (1997)	225	5.5	SSS	AAI vs VVI	All-cause mortality, CV mortality, AF, stroke, HF, and AV block	Significant reduction in CV mortality, AF, stroke and HF in the AAI group
PASE[11] (1998)	407	1.5	SSS and AVB	DDDR vs VVIR	Quality of life, all-cause mortality1, HF1, and AF1	No overall difference in quality of life albeit moderate improvement in patients with SSS but not AVB in the DDDR group No difference in mortality, HF or AF
CTOPP[9] (2000)	2568	6.4	SSS and AVB	DDD/AAI vs VVI(R)	Stroke, CV mortality, all-cause mortality1, AF1, and HF1	No difference in stroke, CV mortality, all-cause mortality or HF Significant reduction in AF in the DDD/AAI group.
MOST[10] (2002)	2010	2.8	SSS	DDDR vs VVIR	All-cause mortality, stroke, AF1, HF1, QoL1, pacemaker syndrome1	No difference in all-cause mortality, stroke Significant reduction in AF, HF, and QoL in the DDDR group 18.3% cross-over due to pacemaker syndrome in the VVIR group
UK-PACE[14] (2005)	2021	3	AVB	DDD(R) vs VVI(R)	All-cause mortality, AF1, HF1, stroke1	No difference in any of the endpoints
DANPACE[13] (2011)	1415	5.4	SSS	AAIR vs DDDR	All-cause mortality, AF1, HF1, stroke1, need for pacemaker reoperation1	No difference in all-cause mortality, chronic AF, HF or stroke Increased risk of paroxysmal AF and need for pacemaker reoperation (development of AVB) in the AAIR group
DAVID[7] (2002)	506	0.8	Primary and secondary prevention ICD	VVI 40 vs DDDR 70 ICD	Composite of hospitalization for HF and mortality	Prematurely interrupted due to increased occurrences of the composite endpoint in the DDDR 70 group
MADIT II substudy[17] (2005)	1232	1.7	Primary prevention ICD	0%-50% vs 51%-100% VP	Composite of HF and mortality	Nearly two-fold increase in hospitalization for HF in the 51%-100% VP group

¹Secondary endpoints. AF: Atrial fibrillation; AVB: Atrioventricular block; CV: Cardiovascular; HF: Heart failure; ICD: Implantable cardioverter-defibrillator; QoL: Quality of life; SSS: Sick sinus syndrome; VP: Ventricular pacing; VVI: Ventricular.

Table 2 Pacemaker algorithms that reduce right ventricular pacing

Reverse Mode Switch/RYTHMIQ™ (Boston Scientific, St. Paul, MN, United States)

Atrial based pacing in AAI(R) with VVI backup (LRL minus 15/min) with the two modes operate independently from one another. If complete AVB occurs, ventricular paces will be delivered at backup VVI rate, asynchronous to the AAI rate. If 3 slow ventricular beats are detected in a window of 11 beats, AV conduction is considered blocked and switch to DDD (R) takes place. The algorithm will switch back to AAI if intact AV conduction is recuperated

Managed Ventricular Pacing™ (Medtronic, Minneapolis, MN, United States)

Atrial based pacing (labeled as AAI(R)+) with switch to DDD(R) if AV block is detected, defined as 2/4 absent ventricular event. The algorithm checks for AV conduction at regular intervals and if present it will switch back to AAI(R)+

Ventricular Intrinsic Preference™ (St. Jude Medical, Sylmar, CA, United States)

Intrinsic AV conduction is assessed by increasing AV delay at regular intervals (programmable AV extension of up to 200 ms; maximum AV delay 350 ms). If present, the longer AV delay will be maintained until a programmable number of cycles of absent ventricular sensed events (i.e., continuous need for ventricular pacing), thus deactivating the algorithm

AV hysteresis (Biotronik, Berlin, Germany)

Similar to Ventricular Intrinsic Preference™ (St. Jude)

AAISafeR™ and AAISafeR2™ (Sorin Group, Mirandola, Italy)

Atrial based pacing in AAI (R). Abnormal AV intervals (> 350 ms if atrial sensed; > 450 ms if atrial paced) are monitored. Switch to DDD in response to any of the following:

> 6 abnormal AV intervals (“first degree AVB”)

> 3/12 nonconducted atrial events (“second degree AVB”)

> 2 consecutive nonconducted atrial event (“advanced AVB”)

Ventricular pauses of 2–4 s (programmable)

AV: Atrioventricular; AVB: Atrioventricular block; LRL: Lower rate limit; VVI: Ventricular.

Table 3 Clinical studies of pacemaker algorithms that minimize right ventricular pacing

Study	Design	Pacing	Patients	Follow-up	Outcomes
		indication	(n)	(mo)
Sweeney et al[30]	Randomized, crossover MVP vs DDD(R)	SSS	181	1	Amount of pacing: MVP™: 4.1%; DDD(R): 73.8%
Murakami et al[29]	Randomized, crossover MVP vs Search AV+	SSS and AVB	127	1	Amount of pacing: MVP: 66.1%; Search AV+: 54.3% (patients with %RVP < 40) MVP: 57.5%; Search AV+: 38.6% (patients with %RVP < 10)
Olshansky et al[32]	RCT DDD(R) AVSH 60/min vs VVI 40/min (non-inferiority)	ICD1	1530	10.4	Trend towards a lower rate of death and hospitalization for HF in the DDD(R) AVSH group
Sweeney et al[33]	RCT Search AV+/MVP vs DDD(R)	SSS	1065	12	Amount of pacing: DDD(R): 99%; Search AV+/MVP: 9.1% Reduction in time to development of AF (primary endpoint) in the search AV+/MVP group No difference in hospitalization for HF or death (secondary endpoints)
Sweeney et al[36]	RCT MVP 60/min vs VVI 40/min (non-inferiority)	ICD1	1030	29	Prematurely interrupted due slightly more deaths and hospitalization for HF in MVP group

¹Patients with an implantable cardiac defibrillator indication were included in the trial; AVB: Atrioventricular block; AVSH: AV Search Hysteresis (Medtronic); MVP: Managed Ventricular Pacing (Medtronic, Minneapolis, MS, United States); ICD: Implantable cardiac defibrillator; RCT: Randomized control trial; RVP: Right ventricular pacing; SSS: Sick sinus syndrome; VVI: Ventricular.

Table 4 Clinical studies of right ventricular pacing vs cardiac resynchronization therapy

Study	Design	Patient	Patients	Follow-up	Baseline LVEF	LVEF in RV	LVEF in CRT	Clinical benefit from CRT
		characteristics	(n)	(mo)		pacing
Martinelli et al[42]	RCT multicenter	AVB	60	5 (crossover)	30.1% ± 9.2%	22.5% ± 8.1%	29.3% ± 6.9%a	Improved NYHA class and QoL
Yu et al[45]	RCT multicenter	AVB and SSS	177	12	61.6% ± 6.6%	54.8% ± 9.1%	62.2% ± 7%b	No difference in hospitalization for HF, exercise capacity or QoL
Curtis et al[41]	RCT multicenter	AVB	691	37	43% ± 7% (CRT-P) 33% ± 8% (DRT-D)	-	-	Reduction in composite endpoint (mortality, HF urgent care and LVESI)
Brignole et al[47]	RCT multicenter	AVN ablation	186	20	38% ± 14%	Increasing from baseline + 4.7%	Increasing from baseline +6.6% (NS)	Reduction in composite endpoint (death from HF, hospitalization for HF or worsened HF)
Doshi et al[49]	RCT multicenter	AVN ablation	184	6	46% ± 16%	41.1% ± 13%	46% ± 13%a	Improved exercise capacity
								No difference in QoL
Orlov et al[51]	RCT multicenter	AVN ablation	127	6	56.1% ± 9.4% (CRT group) 57.2% ± 7.5% (RVP group)	54.6% ± 11.5%	59.3% ± 7.7%a	No difference in NYHA class, exercise capacity or QoL

^aP < 0.05;

^bP < 0.001 vs left ventricular function in right ventricle pacing; AVB: Atrioventricular block; AVN: Atrioventricular node; CRT-D: Cardiac resynchronization with implantable cardiac defibrillator; CRT-P: Cardiac resynchronization therapy pacing; NS: Non-significant; RVP: Right ventricular pacing; SSS: Sick sinus syndrome; QoL: Quality of life; LVEF: Left ventricular function; RV: Right ventricle; LVESI: Left ventricular end-systolic index; HF: Heart failure; RCT: Randomized controlled trial.