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Kusumoto et al 2018 Bradycardia Clinical Practice Guidelines

Circulation. 2019;140:e382–e482. DOI: 10.1161/CIR.0000000000000628 August 20, 2019 e431 CLINICAL STATEMENTS AND GUIDELINES

ventricular pacing did not show a mortality benefit or a lower incidence of AF or heart failure in the patients with dual chamber pacing. For the combined outcome of stroke, transient ischemic attack, and other thromboembolism, the mean annual rate was not different between the 2 groups.S6.4.4.1-8,S6.4.4.1-33 Furthermore, there was a significantly higher risk of procedural complications in the dual chamber group (7.8% versus 3.5%; P<0.001). Similarly, the MOST and CTOPP studies did not show any all-cause mortality or cardiovascular death reduction in the dual chamber group.S6.4.4.1-2–S6.4.4.1-4,S6.4.4.1-8 Therefore, although dual chamber devices provide atrioventricular synchrony and are generally preferable, it is reasonable to implant a single chamber ventricular pacing system in patients who do not need the chronotropic support from atrial pacing and who have significant comorbidities or limited mobility. In addition, for patients who will only require intermittent pacing support, single chamber ventricular pacing can be a reasonable option. Patients who require intermittent or occasional pacing are less likely to develop symptoms of pacemaker syndrome such as exertional intolerance and hypotension.S6.4.4.1-1 3.	 Patients who are in sinus rhythm with single chamber ventricular pacing can develop symptoms of pacemaker syndrome such as exertional intolerance and hypotension. Patients with a high burden of ventricular pacing and intact ventriculoatrial conduction are more likely to develop symptoms of pacemaker syndrome.S6.4.4.1-9,S6.4.4.1-10 If the risk of pacemaker syndrome seems likely because of frequent sinus bradycardia and a high likelihood of frequent pacing, then a ventricular lead only device will probably be inadequate. Pacemaker syndrome was diagnosed in >18% of patients with the single chamber ventricular pacing mode in the MOST trial; however, ultimately a total of 31.4% had crossed over to dual chamber pacing.S6.4.4.1-2,S6.4.4.1-9 Predictors included a lower intrinsic sinus rate and a higher programmed pacing rate.S6.4.4.1-9 Similarly, a 26% crossover rate from the VVI to DDD pacing mode was seen in the PASE trial with predictors of pacemaker syndrome including decreased systolic blood pressure during pacing and use of beta blockers.S6.4.4.1-1,S6.4.4.1-10 Although there was a lower crossover rate in CTOPP and UKPace (approximately 3%), these patients would have required a system revision to a dual chamber system rather than reprogramming the pacing mode.S6.4.4.1-

3,S6.4.4.1-8 Therefore, in patients likely to develop pacemaker syndrome symptoms, a dual chamber device is preferred to avoid an additional procedure to revise the device in the future. 4.	 The deleterious effects of chronic RV pacing have been demonstrated in various studies, although only a minority of chronically RV paced individuals will develop ventricular dysfunction or heart failure symptoms.S6.4.4.1-7,S6.4.4.1-34–S6.4.4.1-36 The DAVID (Dual Chamber and VVI Implantable Defibrillator) trial, a defibrillator trial comparing dual chamber pacing at 70 bpm to “back-up” pacing at 40 bpm, found that ICD patients without a pacing indication had an increased combined endpoint of death and hospitalization with dual chamber pacing.S6.4.4.1-7 Some studies have suggested that the risk of RV pacing induced cardiomyopathy increases when RV pacing exceeds 40% or perhaps as low as 20%.S6.4.4.1-6,S6.4.4.1-34,S6.4.4.1-37 The BLOCK HF trial (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block), which compared CRT and RV pacing in patients with an LVEF of ≤50% and atrioventricular block, showed a significant reduction in the combined primary endpoint of an increase in left ventricular end-systolic volume index by 15%, a heart failure urgent visit, or death. Although some patients had an LVEF ≤35%, most CRT-P subjects had an LVEF of >35% with a mean LVEF of 42.9% (approximately 60% of the total cohort). A mortality benefit was not shown, but there was a significant reduction in HF hospitalizations (HR: 0.68; 95% CI: 0.49–0.94). Subsequent studies have also shown a reduction of left ventricular end-systolic volume and an improvement in LVEF with CRT compared with RV pacing in patients with relatively preserved LVEF.S6.4.4.1-15,S6.4.4.1-19,S6.4.4.1-21,S6.4.4.1-36 In patients with AF who undergo atrioventricular node ablation to control rapid ventricular rates, physiologic pacing (CRT or His bundle) was associated with significant improvements in patient-centered outcomes such as 6-minute walk distances and QOL compared with RV pacing.S6.4.4.1-19 An analysis by the evidence review committee suggests that there may be some benefit associated with physiologic ventricular activation by CRT or His bundle pacing .S6.4.4.1-19

5.	 Predictors of RV pacing cardiomyopathy include a lower baseline LVEF and a higher percentage of RV pacing.S6.4.4.1-34,S6.4.4.1-37 Some studies showed that the risk of RV pacing induced cardiomyopathy increases when RV pacing exceeds 40% or perhaps as low as 20%.S6.4.4.1-6,S6.4.4.1-34,S6.4.4.1-37 The MOST study (Multicenter Osteoarthritis Study), an RCT looking at dual chamber pacing in SND patients, showed that RV pacing at least 40% of the time led to a 2.6-fold increase in HF hospitalizations.S6.4.4.1-6 Although not directly comparable because it enrolled patients with an

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