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Clinical Outcomes of Selective Versus Nonselective His Bundle PacingFree Access

Focus on New Science From HRS 2019

J Am Coll Cardiol EP, 5 (7) 766–774
Sections

Central Illustration

Abstract

Objectives:

The aim of the study was to evaluate the clinical outcomes of nonselective (NS) His bundle pacing (HBP) compared with selective (S) HBP.

Background:

HBP is the most physiologic form of ventricular pacing. NS-HBP results in right ventricular septal pre-excitation due to fusion with myocardial capture in addition to His bundle capture resulting in widened QRS duration compared with S-HBP wherein there is exclusive His bundle capture and conduction.

Methods:

The Geisinger and Rush University HBP registries comprise 640 patients who underwent successful HBP. Our study population included 350 consecutive patients treated with HBP for bradyarrhythmic indications who demonstrated ≥20% ventricular pacing burden 3 months post-implantation. Patients were categorized into S-HBP or NS-HBP based on QRS morphology (NS-HBP n = 232; S-HBP n = 118) at the programmed output at the 3-month follow-up. The primary analysis outcome was a combined endpoint of all-cause mortality or heart failure hospitalization.

Results:

The NS-HBP group had a higher number of men (64% vs. 50%; p = 0.01), higher incidence of infranodal atrioventricular block (40% vs. 9%; p < 0.01), ischemic cardiomyopathy (24% vs. 14%; p = 0.03), and permanent atrial fibrillation (18% vs. 8%; p = 0.01). The primary endpoint occurred in 81 of 232 patients (35%) in the NS-HBP group compared with 23 of 118 patients (19%) in the S-HBP group (hazard ratio: 1.38; 95% confidence interval: 0.87 to 2.20; p = 0.17). Subgroup analyses of patients at greatest risk (higher pacing burden or lower left ventricular ejection fraction) revealed no incremental risk with NS-HBP.

Conclusions:

NS-HBP was associated with similar outcomes of death or heart failure hospitalization when compared with S-HBP. Multicenter risk-matched clinical studies are needed to confirm these findings.

Introduction

In the normal heart, electrical activation of the ventricles occurs along a sophisticated network of His-Purkinje (HP) fibers, resulting in rapid synchronous activation and myocardial contraction. When electrical activation originates in the myocardium, as seen with right ventricular pacing (RVP), ventricular activation occurs slowly using myocyte-to-myocyte conduction resulting in intra- and interventricular dyssynchrony (1).

As a result of pacing induced dyssynchrony, RVP has been associated with a higher incidence of atrial fibrillation, heart failure (HF), and mortality (2–4). These consequences are more likely to be seen with higher pacing burden (5). Recent studies have suggested that a VP burden of 20% or more is associated with increased risk of pacing-induced cardiomyopathy and HF (6,7). These deleterious effects of RVP have generated considerable interest in alternative pacing sites such as biventricular pacing and His bundle pacing (HBP). The feasibility, safety, and clinical benefits of HBP over RVP have recently been demonstrated (8–12).

Depending on the location of the lead in the atrial or ventricular aspects of the membranous septum, the anatomic variations of the His bundle, and underlying HP conduction disease, HBP can result in no or varying degrees of myocardial fusion. Recommended nomenclature of morphologies noted during HBP have recently been standardized by a multicenter HBP collaborative working group (13). Selective (S) HBP implies capture of the HB alone with resulting conduction via the HP axis resulting in a QRS duration and morphology identical to the native QRS duration (in patients without HP axis disease) and an isoelectric period that equals the His-V interval. In nonselective (NS) HBP, capture of the septal myocardium in addition to HB capture results in RV myocardial pre-excitation before the rapid activation of the ventricles via HP axis resulting in initial slurring (pseudo-delta wave) and widening of the QRS complex (Figure 1). In both S- and NS-HBP, the left ventricular (LV) activation occurs via the native conduction system maintaining LV synchrony and is expected to prevent adverse clinical outcomes. However, it is unknown whether the RV myocardial pre-excitation and resultant QRS prolongation during NS-HBP would result in adverse clinical outcomes when compared with outcomes for S-HBP. The aim of this study was to evaluate the clinical outcomes for NS-HBP compared with those for S-HBP.

Figure 1.
Figure 1.

S- and NS-HBP

Twelve-lead electrograms in a patient with atrial fibrillation and bradycardia. Baseline QRS duration is 90 ms. During selective (S)–His bundle pacing (HBP), the QRS morphology and duration is identical to baseline. Nonselective (NS)-HBP achieved at a different site in the same patient results in a wider QRS duration of 135 ms.

Methods

Study population

Patients undergoing HBP implantations were enrolled into institutional HBP registries at the Geisinger Heart Institute, starting January 1, 2011, and Rush University Medical Center, starting October 1, 2016. Patients were >18 years of age and required de novo permanent pacemaker implantation for bradycardia based on current guidelines (14). Patients were excluded if they underwent cardiac resynchronization therapy, had existing cardiac implantable electronic devices, had <6 months’ follow-up, or permanent HBP was unsuccessful. All follow-up data were collected until December 2018. The institutional review board at each participating center approved the study protocol.

Procedure

HBP was performed using the Select Secure pacing lead (model 3830, 69 cm, Medtronic, Minneapolis, Minnesota) delivered through a fixed curve or a deflectable sheath (C315HIS and C304, Medtronic) as previously described by our group (15). Briefly, the delivery sheath was inserted into the RV near the tricuspid annulus over a guidewire through the cephalic, axillary, or subclavian veins. Subsequently, the pacing lead was advanced through the sheath such that the distal electrode/screw was beyond the sheath tip. A unipolar electrogram was recorded from the lead tip and displayed on an electrophysiology recording system (Bard, Boston Scientific, Lowell, Massachusetts; or Prucka Cardiolab, GE Healthcare, Waukesha, Wisconsin) and a Medtronic pacing system analyzer (model 2290). HB electrogram was identified by mapping the atrioventricular (AV) septum, and the lead was then screwed in this position by clockwise rotation. When an HB electrogram was not recordable during mapping, pace mapping was performed in a unipolar fashion to identify the successful site. Patients were routinely programmed post-implantation to a VP output of 5 V per 1 ms. During implantation, the practice at both centers was to achieve acceptable His capture thresholds and sensing parameters to avoid programming issues irrespective of S- or NS-paced QRS morphology. In patients with infranodal AV blocks, the intent was to achieve NS-HBP to ensure ventricular capture to provide additional safety in case of progression of HP conduction disease. In our experience, it was very rare to achieve acceptable S-His capture thresholds in patients with infranodal AV block.

Follow-up and clinical outcomes

Patient demographics, medical history, medications, and electrocardiographic and echocardiographic findings were collected. Patients were followed in the device clinic at 2 weeks, 3 months, and yearly thereafter along with quarterly remote device checks. Patients with high-grade and complete AV block were programmed to DDD pacing mode with AV delay shortened by 40 to 50 ms compared with nominal to accommodate the His-V conduction delay. In patients with sinus node dysfunction and intermittent AV block, VP avoidance algorithms were used to minimize VP. VP burden was routinely documented in all patients. Pacing proportion was documented at their 3-month follow-up visit.

At the 3-month visit, patients with only S-HBP (no RV capture) and those with NS-HBP who had RV capture thresholds which were higher than His capture thresholds, chronic pacing outputs were programmed to be at least twice the HB capture threshold to allow for a safety margin for ventricular capture. In patients with NS-HBP who had His capture thresholds which were higher than RV capture thresholds, output was programmed to be at least 1 V above His capture threshold. To assess the impact of NS-HBP on clinical outcomes, patients were categorized as S-HBP or NS-HBP based on the pacing outputs and morphologies noted at the chronic phase-programmed output at the 3-month device-clinic follow-up. Additional confirmation of NS-HBP and S-HBP was performed using surface electrocardiography and/or 12-lead electrocardiograms at the time of device clinic visits. Based on recent studies, we hypothesized that >20% VP burden can lead to adverse clinical outcomes (6,7).

The primary outcome measured was death from any cause or first episode of heart failure hospitalization (HFH). HFH was defined as an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with HF and required intravenous therapy. Information regarding mortality was obtained from hospital records and the social security death index. Secondary outcomes included the individual outcomes of death from any cause and HFH. Outcomes occurring in the first 90 days were screened. Any deaths within the first 90 days were inherently excluded from this study due to failure to meet inclusion criteria (assignment to S-HBP or NS-HBP in follow-up at the chronic phase-programmed output). HFH in the first 90 days were screened during the initial pre-assignment run-in period.

Subgroup analyses were performed among patients at the greatest risk of adverse outcomes from RV myocardial pre-excitation based on known predictors associated with worse outcomes with RVP (4–7) as well as patients with an indication for pacing related to AV conduction disease. AV conduction disease was further stratified and analyzed among patients with nodal disease and infranodal disease.

Statistical analysis

All data were summarized using frequencies and proportions for categorical data and means ± SD or median (interquartile range) for continuous data that are distribution-dependent. The descriptive statistics were reported for the full sample and stratified by S-HBP and NS-HBP groups. Comparison between the groups was accomplished using the chi-square or Fisher exact tests, and Student's 2-sample t-test or Wilcoxon rank sum test, as appropriate. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were used to estimate the survival probability or HFH by the S-HBP and NS-HBP groups. Initially, univariate analysis was done on variables previously determined to be clinically significant. Multivariate regression models were then performed on statistically significant hazard ratios (HR) and were subsequently repeated until significance was evident for all variables. Patients’ last follow-up date was determined by the last time they were seen in the Geisinger or Rush Health system or until the time of death, whichever occurred first. All data and follow-up dates were censored after December 31, 2018. For the Kaplan-Meier curves and Cox regression risk analysis, time censoring was determined by time to event (primary or secondary) or time to last follow-up in the Geisinger or Rush Health systems, whichever came first. Follow-up assessment for the primary and secondary outcomes were initiated at 90 days post-device implantation. Statistical analysis was performed using SPSS version 25 (IBM Corp., Armonk, New York). A p value of <0.05 was considered significant.

Results

Baseline characteristics

A total of 640 patients underwent successful permanent HBP implantation during the study period at the 2 sites. Of these, 350 patients met the inclusion criteria with a ≥20% VP burden at the 3-month follow-up and formed the study group.

The mean age was 75 ± 10 years of age, with male patients accounting for 59% of the study cohort. History of HF and atrial fibrillation was present in 34% and 60%, respectively. Mean baseline left ventricular ejection fraction (LVEF) of the entire cohort was 54.8 ± 8.4%, and mean baseline QRS duration was 110 ± 28 ms. Based on the indications for pacemaker implantation, 20% of the patients had sinus node dysfunction and the remaining 80% had AV conduction disease. The mean follow-up duration for the entire cohort was 1,022 ± 674 days.

Based on the chronic-phase programmed pacing output and paced QRS morphology at 3-month follow-up, NS-HBP was noted in 232 patients (67%) while the remaining 118 patients (33%) had S-HBP. Table 1 illustrates the baseline characteristics of the patients in these groups. There were several differences in baseline characteristics between the 2 groups. There was a higher number of male patients (64% vs. 50%; p = 0.01), higher incidence of infranodal AV block (40% vs. 9%; p < 0.01), permanent atrial fibrillation (18% vs. 8%; p = 0.01), coronary artery disease (36% vs. 25%; p = 0.04) and ischemic cardiomyopathy (24% vs. 14%; p = 0.03) in the patients with NS-HBP as compared to those with S-HBP. The paced QRS duration was significantly wider in the NS-HBP group (139 ± 21 ms vs. 103 ± 18 ms; p < 0.01) compared with in the S-HBP group despite similar baseline QRS duration between the 2 groups (111 ± 26 ms vs. 107 ± 30 ms, respectively; p = 0.24). There was no significant difference in the HBP capture threshold from implantation to last follow-up between NS-HBP and S-HBP groups (Table 2). A higher incidence of beta blocker use (76% vs. 64%; p = 0.02), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (75% vs. 64%; p = 0.02), and anticoagulation with either direct-acting oral anticoagulants or vitamin-K antagonists (52% vs. 40%; p = 0.03) was noted in the NS-HBP group, while a higher proportion of patients in the S-HBP group were on amiodarone (30% vs. 20%; p = 0.05).

Table 1. Baseline Patient Characteristics

NS-HBP (n = 232)S-HBP (n = 118)p Value
Age, yrs75 ± 1074 ± 100.54
Body mass index, kg/m229 ± 629 ± 60.56
Male148 (64)59 (50)0.01
Caucasian221 (95)99 (84)<0.01
Medical history
Smoking123 (53)44 (37)<0.01
Hypertension188 (81)92 (78)0.50
Hyperlipidemia172 (74)58 (49)<0.01
Atrial fibrillation137 (59)72 (61)0.72
Permanent atrial fibrillation41 (18)9 (8)0.01
Diabetes mellitus105 (45)41 (35)0.06
Coronary artery disease84 (36)30 (25)0.04
Percutaneous coronary intervention39 (17)9 (8)0.02
Coronary artery bypass surgery49 (21)20 (17)0.35
Chronic kidney disease91 (39)47 (40)0.91
Baseline creatinine1.2 ± 0.81.3 ± 1.10.31
Congestive heart failure90 (39)35 (30)0.09
NYHA functional class III or IV31 (13)3 (2.5)<0.01
Ejection fraction, %55 ± 855 ± 100.55
Ischemic cardiomyopathy55 (24)16 (14)0.03
Stroke28 (12)11 (9)0.44
Liver disease19 (8)4 (3)0.09
Medication history
Beta-blocker176 (76)76 (64)0.02
ACE/ARB175 (75)75 (64)0.02
Potassium-sparing diuretic23 (10)9 (8)0.48
Loop diuretic126 (54)57 (48)0.29
Class IC antiarrhythmic17 (7)9 (8)0.92
Class III antiarrhythmic75 (32)43 (36)0.44
Amiodarone47 (20)35 (30)0.05
Anticoagulation121 (52)47 (40)0.03

Values are mean ± SD or n (%).

ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; HBP = His bundle pacing; NS = nonselective; NYHA = New York Heart Association; S = selective.

∗ p < 0.05 was considered statistically significant.

Table 2. Baseline Pacemaker Characteristics

NS-HBP (n = 232)S-HBP (n = 118)p Value
Single-chamber pacemaker43 (19)9 (8)<0.01
Dual-chamber pacemaker189 (81)109 (92)<0.01
Sinus node dysfunction37 (16)33 (28)<0.01
AV conduction disease195 (84)85 (72)<0.01
Infranodal disease78 (40)8 (9)<0.01
Baseline QRS duration, ms111 ± 26107 ± 300.24
Narrow QRS143 (62)84 (71)0.08
Left bundle branch block20 (9)12 (10)0.63
Right bundle branch block57 (25)20 (17)0.10
IVCD12 (5)2 (2)0.12
Paced QRS duration, ms139 ± 21103 ± 18<0.01
VP, %89 ± 2187 ± 230.38
Vp >40%219 (94)106 (90)0.12
QRS duration change+27 ± 31−5 ± 28<0.01
HBP threshold at implantation1.3 ± 0.81.3 ± 0.90.87
HBP threshold at last follow-up1.5 ± 1.01.7 ± 1.00.21
HBP programmed output, chronic2.8 ± 1.13.1 ± 1.20.15

Values are mean ± SD or n (%).

AV = atrioventricular; IVCD = interventricular conduction delay not meeting left or right bundle patterns; VP = ventricular pacing; other abbreviations as in Table 1.

∗ p < 0.05 was considered statistically significant.

Clinical outcomes

The primary outcome (combined endpoint of death from any cause or HFH) occurred in 81 of the 232 patients (35%) in the NS-HBP group versus 23 of the 118 patients (19%) in the S-HBP group (HR: 1.38; 95% confidence interval [CI]: 0.87 to 2.20; p = 0.17) (Central Illustration, Table 3). Whereas there was a trend favoring S-HBP, this did not reach statistical significance. The only multivariate predictors of increased risk for primary outcome were age, history of congestive HF, and AV conduction disease as the indication for permanent pacemaker. Univariate regression analysis of the HR imparted by implanting center was calculated anonymously for purposes of potential HR adjustment in multivariate analysis and was not found to be statistically significant.

Central Illustration.
Central Illustration.

Primary Outcome of Death or HFH

Cox-proportional hazards survival curves and analysis of the primary endpoint in patients with selective (S)–His bundle pacing (HBP) versus nonselective (NS)-HBP. HFH = heart failure hospitalization; HR = hazard ratio.

Table 3. Univariate and Multivariate HR for Composite Outcome of All-Cause Death or HFH

UnivariateMultivariate
HR95% CI Lower95% CI Upperp ValueHR95% CI Lower95% CI Upperp Value
NS-HBP1.5480.9732.4630.0651.3820.8672.2040.174
Age1.0471.0221.0720.0001.0481.0231.0730.000
Smoking1.3230.8931.9610.163
Male1.4100.9252.1490.110
Hyperlipidemia2.0431.1943.4970.009
Hypertension1.2800.7892.0770.318
Diabetes mellitus1.4320.9752.1050.067
Chronic kidney disease2.0621.4003.0370.000
Hemorrhagic stroke0.4950.0693.5550.485
Ejection fraction <50%1.7241.0312.8830.038
Pacing burden >40%1.8800.7644.6260.169
Ischemic stroke1.0560.6011.8570.850
Coronary artery disease1.2240.8181.8320.326
Percutaneous coronary intervention1.0230.5911.7700.936
Coronary artery bypass surgery1.6141.0492.4830.029
Ischemic cardiomyopathy1.7801.1452.7660.010
Congestive heart failure2.0451.3903.0070.0002.0901.4193.0780.000
Atrial fibrillation1.1440.7621.7170.516
Caucasian2.2640.5549.2570.255
AV conduction disease2.0631.1033.8570.0232.2771.2104.2850.011
Infranodal disease1.2880.8521.9470.231
Baseline QRS duration1.0000.9931.0070.974
Paced QRS duration1.0060.9981.0130.148
Liver disease0.8330.3382.0500.691
Beta blocker therapy1.2320.7751.9590.377
ACE or ARB therapy1.1040.7031.7340.666
Antiarrhythmic therapy0.8530.5711.2720.435
Anticoagulation1.2650.8561.8680.238
Implanting center2.5420.7918.1720.117

ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CI = confidence interval; HFH = heart failure hospitalization; HR = hazard ratio; other abbreviations as in Tables 1 and 2.

∗ p < 0.05 was considered statistically significant.

The secondary endpoint of all-cause mortality occurred in 28% of patients (65 of 232) in the NS-HBP group and 14% of patients (16 of 118) in the S-HBP group (HR: 1.65; 95% CI: 0.96 to 2.86; p = 0.07) (Table 4). HFH occurred in 9% of patients (21 of 232) in the NS-HBP group and 7% of patients (8 of 118) in the S-HBP group (HR: 0.96; 95% CI: 0.42 to 2.20; p = 0.93) (Table 4, Figure 2).

Table 4. Comparison of Secondary Outcomes Between NS-HBP and S-HBP

NS-HBPS-HBPp ValueUnivariateMultivariate
HR95% CI Lower95% CI Upperp ValueHR95% CI Lower95% CI Upperp Value
All-cause mortality65 (28)16 (14)<0.011.7431.0073.0150.0471.6540.9552.8630.072
Heart failure hospitalization21 (9)8 (7)0.471.1680.5142.6520.7110.9610.4202.2000.925

Values are n (%), unless otherwise indicated.

Abbreviations as in Tables 1 and 3.

∗ p < 0.05 was considered statistically significant.

Figure 2.
Figure 2.

Secondary Outcomes

Cox-proportional hazards survival curves and analysis of the all-cause mortality (left) and heart failure hospitalization (right) in patients with selective (S)- and nonselective (NS)–His bundle pacing (HBP). HR = hazard ratio.

Subgroups analysis

Patients were further stratified and analyzed based on reduced LVEF <50%, VP burden, and presence and type of AV conduction disease (for baseline characteristics, see Online Table 1).

In patients with a baseline LVEF <50%, which accounted for 12% of all patients (41 of 350), the primary endpoint was met in 56% of patients (15 of 27) in the NS-HBP group versus 21% of patients (3 of 14) in the S-HBP group (HR: 2.30; 95% CI: 0.64 to 8.28; p = 0.20) (Table 5). Baseline differences between the 2 groups are highlighted in Online Table 1.

Table 5. Comparison of the Primary Outcome (All-Cause Mortality and HFH) in Subgroup Analyses Between NS-HBP and S-HBP Patients With a Pacing Burden >20%

NS-HBPS-HBPp ValueUnivariateMultivariate
HR95% CI Lower95% CI Upperp ValueHR95% CI Lower95% CI Upperp Value
Left ventricular ejection fraction <50% (n = 41)15/27 (56)3/14 (21)0.042.2480.6507.7750.2012.3000.6398.2750.202
Ventricular pacing burden >40% (n = 325)77/219 (35)22/106 (21)0.011.5160.9402.4430.0881.3110.8122.1160.267
AV conduction disease (n = 280)73/195 (37)20/85 (24)0.021.4350.8732.3580.1541.3310.8102.1890.259
Nodal conduction disease (n = 194)44/117 (38)16/77 (21)0.011.7130.9633.0470.0671.5170.8462.7220.162
Infranodal conduction disease (n = 86)29/78 (37)4/8 (50)0.480.6410.2231.8430.4090.7250.2482.1200.557

Values are n/N (%), unless otherwise indicated.

Abbreviations as in Tables 1, 2, and 3.

∗ p < 0.05 was considered statistically significant.

In patients with VP burden >40%, the primary outcome occurred in 35% of patients (77 of 219) in the NS-HBP group versus 21% patients (22 of 106) in the S-HBP group (HR: 1.31; 95% CI: 0.81 to 2.12; p = 0.27) (Table 5). Among patients with AV conduction disease, the primary endpoint was noted in 37% of patients (73 of 195) in the NS-HBP group versus 24% of patients (20 of 85) in the S-HBP group (HR: 1.33; 95% CI: 0.81 to 2.19; p = 0.259). In the subgroup with AV nodal disease, 38% of patients (44 of 117) in the NS-HBP group reached the primary endpoint versus 21% of patients (16 of 77) in the S-HBP group (HR: 1.52; 95% CI: 0.85 to 2.72; p = 0.16). In patients with infranodal disease, the primary endpoint occurred in 37% of patients (29 of 78) in the NS-HBP group versus 50% of patients (4 of 8) in the S-HBP group (HR: 0.73; 95% CI: 0.25 to 2.12; p = 0.56) (Table 5).

Discussion

The results from this study demonstrate that NS-HBP was not associated with a statistically significant increase in the risk of combined endpoint of all-cause mortality or HFH when compared with S-HBP in patients undergoing de novo permanent pacemaker implantation for bradycardia and requiring ≥20% VP. Subgroup analysis of patients expected to be at higher risk for RVP induced ventricular dyssynchrony, and those with reduced LVEF as well as those with >40% pacing burden, further showed that there was no significant adverse outcomes from NS-HBP when compared with S-HBP. Whereas there were trends in primary outcomes in favor of S-HBP in this study without reaching statistical significance, baseline differences showed higher comorbidities in the NS-HBP group.

The MOST (MOde Selection Trial in Sinus-Node Dysfunction) study (2) demonstrated that patients with VP in excess of 40% had a 2.5×greater risk of HFH than those patients with <40% pacing. More recent studies suggest that a VP burden as low as 20% is associated with an increase in HFH risk (6,7). Similarly, patients with LVEF <50% are likely to be adversely effected by RVP (particularly patients with clinical heart failure) (1,16). Our results demonstrate that NS-HBP was not associated with a statistically significant risk in this subgroup (HR: 2.3; p = 0.20). Furthermore, analysis of patients based on the type of conduction disease (nodal or infranodal) also did not show a significant difference in outcomes between NS-HBP and S-HBP groups. During S- and NS-HBP, the LV activation is rapid and synchronous. Thus the RV pre-excitation seen with NS-HBP is unlikely to result in adverse clinical outcomes in patients expected to have a high VP burden (even those at highest risk).

Whereas isolated HB capture as seen with S-HBP is aesthetically pleasing on electrocardiography and is the most physiologic form of pacing, success in achieving S-HBP is based on a multitude of factors and may not be possible in all patients. Based on our years of experience with HBP and for practical considerations, our primary goal during HBP lead implantations was to achieve acceptable sensing parameters and His capture thresholds rather than target S-HBP. Determinants of S-HBP also depends, among others, on lead location in relation to the tricuspid valve, anatomic variations of the course of the HB, and level of disease. The presence of large atrial electrograms and lower amplitude ventricular electrograms on the atrial aspect of the HB in the membranous septum may lead to sensing issues that may not allow the implanter to accept S-HBP even when excellent pacing thresholds are achieved. NS-HBP is often preferred to avoid ventricular undersensing in this situation. In patients with evidence of infranodal HP conduction disease, and in patients undergoing AV nodal ablation, NS-HBP is preferred because of the backup “safety” pacing provided by the RV septal myocardial capture.

Whereas randomized clinical studies will ideally be necessary to confirm these findings, it may not be clinically feasible for the reasons discussed in this paper. Under these circumstances, we believe that our study provides plausible evidence that NS-HBP, compared with S-HBP, is not associated with adverse clinical outcomes.

Study limitations

This was an observational study of consecutive patients receiving successful de novo HBP implantation from Geisinger Heart Institute and Rush University Medical Center. NS- and S-HBP were determined by the patient’s anatomy, implantation characteristics, and underlying conduction disease rather than by randomization. Due to the nonrandomized nature, this study does not ensure homogeneity of the subgroups. The results should therefore be interpreted with caution. Given the fact that various factors determine NS- or S-HB capture at implantation, it would be very challenging and not practical to perform a randomized study specifically looking at the differences between to S- and NS-HBP. NS-HBP can result in varying degrees of fusion (varying QRS width) between HB and myocardial capture. However, the specific differences in outcomes between a narrower and wider paced QRS duration with NS-HBP were not assessed in this study. Furthermore, echocardiographic follow-up data were not available for all patients in the cohort and hence were not reported. Finally, due to the slight trend toward better outcomes with S-HBP in this study, it is possible that there may be a difference in outcomes that is not realized in this study size (type II error).

Conclusions

NS-HBP was associated with similar outcomes of death or HFH as S-HBP in patients with ≥20% VP burden.

Perspectives

COMPETENCY IN MEDICAL KNOWLEDGE: NS-HBP results in myocardial fusion capture in addition to HB capture. NS-HBP, compared with S-HBP, was not associated with increased risk for combined endpoint of all-cause mortality or HFH.

TRANSLATIONAL OUTLOOK: Additional randomized or risk-matched multicenter studies with long-term follow-up are necessary to confirm the clinical benefits of S- versus NS-HBP in patients requiring VP.

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Abbreviations and Acronyms

AV

atrioventricular

CI

confidence interval

LVEF

left ventricular ejection fraction

HB

His bundle

HBP

His bundle pacing

HF

heart failure

HFH

heart failure hospitalization

HP

His-Purkinje

HR

hazard ratio

LV

left ventricle

NS

nonselective

RV

right ventricle

RVP

right ventricular pacing

S

selective

VP

ventricular pacing

Footnotes

Dr. Sharma has received speaking honoraria from Medtronic; and consulting honoraria from Medtronic, Abbott, and Biotronik. Dr. Subzposh has received speaking honoraria from Medtronic. Dr. Trohman has served on the advisory board of Boston Scientific/Guidant; has received research grants from Boston Scientific/Guidant, Medtronic, St. Jude Medical (Abbott), Vitatron, and Wyeth-Ayerst/Wyeth Pharmaceuticals; has received consulting honoraria from Biosense Webster, St. Jude Medical (Abbott), and AltaThera Pharmaceuticals; has received speaking or other honoraria from Boston Scientific/Guidant, Medtronic, Daiichi Sankyo, AltaThera Pharmaceuticals, and St. Jude Medical (Abbott). Dr. Dandamundi has received speaking and consulting honoraria and research funding from Medtronic. Dr. Vijayaraman has received speaking honoraria and research funding from Medtronic; has received consulting honoraria from Medtronic, Boston Scientific, Abbott, and Biotronik; and has a patent pending for a His delivery tool. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.