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Clinical Electrophysiology

Editor-in-Chief

Dr. David J. Wilber.

J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 1 , N O . 6 , 2 0 1 5

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Electrophysiologic Insights IntoSite of Atrioventricular Block

Lessons From Permanent His Bundle Pacing

Pugazhendhi Vijayaraman, MD,* Angela Naperkowski, RN, CCDS, CEPS,* Kenneth A. Ellenbogen, MD,yGopi Dandamudi, MD*

ABSTRACT

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OBJECTIVES This study sought to report the feasibility of permanent His bundle pacing (HBP) in patients with advanced

atrioventricular block (AVB) and electrophysiological observations into site of block in patients with infranodal AVB.

BACKGROUND HBP is a physiological alternative to right ventricular pacing. Historic studies have reported a low

incidence of intra-His AVB. Recent studies of permanent HBP reported limited success in patients with infranodal AVB.

METHODS Consecutive patients with advanced AVB underwent permanent HBP using Medtronic 3830 lead

(Minneapolis, Minnesota) and a fixed-shaped catheter (C315 His). The HB was mapped using unipolar recording from

the lead tip or by pace mapping. Success of HBP, type of AVB, and pacing outcomes were documented. Patients were

followed at 2 weeks, 2 months, and then yearly.

RESULTS A total of 100 patients with advanced AVB (age 75 � 12 years; male 62%; AV nodal 46%; infranodal 54%)

underwent permanent HBP. HBP was successful in 84 patients (84%; AV nodal 93%, infranodal 76%). Mean procedure

time was 71 � 21 min, mean fluoroscopy time was 11 � 6 min. Baseline QRS duration was 122 � 27 ms; paced QRSd was

124 � 22 ms. The HB pacing threshold at implant, 2 weeks, 2 months, and last follow-up (19 � 12 months; range: 6 to 46

months) was 1.3 � 0.9 V, 1.6 � 1.0 V, 1.6 � 1.1 V, and 1.7 � 1.0 V at 0.5 ms, respectively. Five patients required lead

revision.

CONCLUSIONS Permanent HBP was successful in 84% of unselected patients with AVB. His-Purkinje conduction could

be normalized in 76% of patients with infranodal block, suggesting intra-His block. Incidence of infra-His AVB was low

(24%) in this series. Routine HBP in patients with AVB is feasible and safe for at least up to 18 months.

(J Am Coll Cardiol EP 2015;1:571–81) © 2015 by the American College of Cardiology Foundation.

T he right ventricular (RV) apex is the mostcommonly used site for ventricular pacingin patients with atrioventricular (AV) conduc-

tion disease and bradycardia. RV apical pacinghas been associated with ventricular dyssynchrony,reduction in left ventricular (LV) ejection fraction,and adverse clinical outcomes (1–5). RV outflow tractand septum have been used as alternative siteswithout proven clinical benefit (6–8). Cardiacresynchronization therapy has been proposed as

m the *Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsy

alth System, Richmond, Virginia. Dr. Vijayaraman has been a speaker fo

ston Scientific. Dr. Ellenbogen has received honoraria, consulting fees, an

d St. Jude Medical; and honoraria and consulting fees from Biotronik. Dr

er authors have reported that they have no relationships relevant to the

nuscript received June 22, 2015; revised manuscript received September

an alternative to RV pacing in patients with heartblock and heart failure (9).

After the original description of permanent Hisbundle pacing (HBP) by Deshmukh et al. (10) in 2000,there have been multiple reports on permanent HBPdemonstrating its feasibility (11–16). Permanent HBPhas been successfully performed in patients with AVblock (AVB) and preserved His-Purkinje conduction,but the success rates have varied from 52% to84% (10,15–18). Interestingly, HBP can also correct

lvania; and the yVirginia Commonwealth University

r Medtronic; and served on the advisory board for

d research grants from Medtronic, Boston Scientific,

. Dandamudi has been a speaker for Medtronic. All

contents of this paper to disclose.

1, 2015, accepted September 24, 2015.

ABBR EV I A T I ON S

AND ACRONYMS

AV = atrioventricular

AVB = atrioventricular block

HB = His bundle

HBP = His bundle pacing

NS-HBP = nonselective His

bundle pacing

RV = right ventricle

S-HBP = selective His bundle

pacing

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infranodal conduction disturbances (17).However, the success rates of permanent HBPin patients with infranodal AVB have beenreported to be very low (19,20). Early studiesusing His bundle (HB) recordings have sug-gested that intra-His block contributes only15% to 20% of patients with infranodal AVB(20–23). More than 70% of infranodal AVB hasbeen attributed to infra-His (distal to the HB)block. We recently reported the feasibilityand clinical outcomes of permanent HBPcompared with RV pacing (16). During this

study, we unexpectedly observed a higher degree ofsuccess in patients with infranodal AVB than previ-ously reported. The aim of our single-center, obser-vational study was to report the success rates andoutcomes of permanent HBP in consecutive patientswith advanced AVB, especially in patients with infra-nodal block.

METHODS

PATIENT SELECTION. From January 2011 to June2014, all patients referred for pacemaker implantationroutinely underwent an attempt at permanent HBPat Geisinger Wyoming Valley Medical Center by 2 ex-perienced operators (P.V., G.D.). Patients undergoingdevice implantation for cardiac resynchronizationtherapy, pulse generator changes, sinus node dys-function, and first- or second-degree AVB were ex-cluded from the study. Patients whomet the followingcriteria were included in the study: 1) complete AVB;2) advanced AVB with 2:1 or greater (3:1) AV conduc-tion ratio; and 3) AV node ablation. This retro-spective study was approved by our institutionalreview board.

HB PACING. HBP was performed using the SelectSecure (Model number 3830, 69 cm, Medtronic Inc.,Minneapolis, Minnesota) pacing lead deliveredthrough a fixed-curve sheath (C315 His, MedtronicInc.), as previously described (15,16). The deliverysheath was inserted into the RV, just beyond thetricuspid annulus. Subsequently, the pacing lead wasadvanced through the sheath such that only the distalelectrode/screw was beyond the tip of the catheter. Aunipolar electrogram was recorded from the lead tip ata gain setting of 0.05 mV/mm and displayed on Med-tronic Pacing System Analyzer (model number 2290) ata sweep speed of 50 mm/s. HB electrogram was iden-tified by mapping the AV septum. The lead was thenscrewed into position with 4 or 5 clockwise rotations.HB capture threshold was assessed and acceptedif found to be <2.5 V at 1.0 ms and only if 1:1

His–ventricular conduction at a minimum of 120 bpmwas demonstrable during pacing. If acceptable HBcapture could not be achieved after 5 attempts at leadpositioning or fluoroscopy duration of <20 min, thelead was then placed in the mid-RV septum. When theHB electrogram was not recordable during mapping,pacing was performed in unipolar fashion to identifythe successful site. During implantation, attemptswere made to obtain selective His bundle pacing(S-HBP) in patients with AV nodal block, but ifHBP with fusion (nonselective His bundle pacing[NS-HBP]) was obtained, this position was accepted. Ifthe patient had infranodal AVB, NS-HBP was preferredto ensure local RV myocardial capture in addition toHB capture. A mapping catheter to locate the HB anda backup RV pacing lead was not routinely used inthese implants. In patients undergoing AV node abla-tion, biventricular pacing using a LV lead in additionto the HBP lead was performed in patients withreduced LV ejection fraction.

DEFINITIONS. S-HBP was defined based on thecriteria published by Williams et al. (24) as evidencedby ventricular activation occurring solely over theHis-Purkinje system. These included: 1) His-Purkinje–mediated cardiac activation and repolarization asevidenced by electrocardiographic concordance ofQRS and T wave complexes; and 2) the paced ven-tricular interval was almost identical to the His–ven-tricular interval (Figure 1).

NS-HBP was defined based on capture of basalventricular septum in addition to HB capture as: 1) noisoelectric interval between pacing stimulus and QRS;2) the electrical axis of the paced QRS must beconcordant with the electrical axis of the sponta-neous QRS (if known); and 3) narrowing of QRS withhigher output. Paced QRS complexes may be nar-rower than the escape rhythm or the conducted beats(Figure 2).

HB and ventricular (myocardial) pacing thresholds,R-wave amplitudes, intracardiac electrograms, andpacing lead impedances were measured at implanta-tion. Total fluoroscopy time and procedure durationfor each patient were recorded. A 12-lead electrocar-diogram at baseline and during HBP, along withbaseline and paced QRS duration, were also recordedfor each patient.

FOLLOW-UP. Patients were followed in the deviceclinic at 2 weeks, 2 months, 1 year, and yearlythereafter. R-wave amplitudes, pacing thresholds,and lead impedances were recorded at each visit.Patients were also followed by remote monitoringevery 3 months. Any significant increases in pacing

FIGURE 1 Selective His Bundle Pacing

(Top) The 12-lead electrocardiogram of a patient with complete heart block with narrow QRS escape rhythm. (Middle) Intracardiac electrogram

recorded from the permanent His bundle pacing lead at the time of implantation. Note the His bundle electrogram (H) with injury current

(arrow) followed by ventricular electrogram (V). (Bottom) His bundle pacing. The pacing spike (circle) is followed by an isoelectric interval of

40 ms and QRS complexes identical to the intrinsic rhythm.

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threshold, lead dislodgement, or loss of capture weretracked routinely.

STATISTICAL ANALYSIS. Normally distributed dataare reported as mean � SD. Absolute frequencies andpercentages are reported for categorical data. Differ-ences between groups were evaluated with Student ttests. All statistical tests were 2-tailed; p < 0.05 wasconsidered to indicate statistical significance. Theelectrical characteristics of the 2 groups in follow-upwere analyzed using repeated-measures analysis ofvariance with a group by time interaction.

RESULTS

Between January 2011 and June 2014, 260 patientsunderwent permanent pacemaker implantation atour institution (HBP was not performed in 2012 dueto nonavailability of Medtronic 3830 pacing leadin the United States). All patients underwent anattempt at permanent HBP. Indications for pacemaker

implantation were sinus node dysfunction in 104 pa-tients (40%) and AV conduction disease in 156 patients(60%). Complete heart block or advanced AVB waspresent in 100 patients (38%; mean age, 75 � 12 years;62 men [62%]) and comprised the study group. AVnodal block was present in 46 patients (46%), and54 patients (54%) had infranodal His–Purkinje disease.At baseline, narrow QRS was seen in 40 patients(40%), andwide QRSwas present in 60 (60%). Baselinecharacteristics are shown in Table 1.

IMPLANT OUTCOMES. Permanent HBP was success-ful in 84 of the 100 patients (84%) with advancedAVB (Figure 3). Single-chamber pacer was implantedin 12 (12%) patients, dual-chamber device in 82 (82%)patients, and biventricular pacer in 6 (6%) patients.Backup RV lead was placed in only 2 of these patients.Mean procedure time was 71 � 21 min (range:36 to 132 min), and mean fluoroscopy duration was11 � 6 min (range: 4 to 46 min).

FIGURE 2 Nonselective His Bundle Pacing

(Top) Baseline 12-lead electrocardiogram of a patient with 2:1 atrioventricular block with right bundle branch block, QRS duration of 120 ms.

(Middle) Intracardiac electrogram from the permanent His bundle pacing lead at the time of implantation. Atrial electrogram (A) is followed by

His (H) and then ventricular (V) electrogram in a 2:1 fashion. (Arrow) His bundle injury current, which resolved in 20 min. (Bottom) atrio-

ventricular sequential pacing. The pacing spike is immediately followed by QRS complexes with evidence for fusion from ventricular and His

bundle capture. Note that the right bundle branch block has also resolved with His bundle pacing, suggesting both the atrioventricular block

and right bundle branch block are at the level of the proximal His bundle.

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S-HBP was achieved in 22 (22%) patients, NS-HBPin 62 (62%) patients, and RV septal pacing in 16(16%) patients. In patients with AV nodal block(n ¼ 46), HBP could not be achieved in 3 (7%) patients(high threshold, n ¼ 2; failure to map HB, n ¼ 1). Inpatients with infranodal AVB (n ¼ 54), HBP was un-successful in 13 (24%) patients (failure to capture andrecruit HB, n ¼ 9; failure to map HB, n ¼ 4).

Permanent HBP was successfully achieved insignificantly more patients with AV nodal blockcompared with patients with infranodal AVB (93% vs.76%; p < 0.05). S-HBP was achieved in 44% of pa-tients with AV nodal block and 7% of patients withinfranodal AVB, and NS-HBP was achieved in 56% ofpatients with AV nodal block and 93% of patients withinfranodal AVB. There were no differences in proce-dure or fluoroscopy duration between the 2 groups(Table 2). Baseline QRS duration was 103 � 20 ms(range: 72 to 145 ms) in AV nodal block patientscompared with QRS duration of 143 � 18 ms

(range: 120 to 186 ms) in patients with infranodalAVB. The paced QRS duration of 114 � 21 ms (range:82 to 150 ms) and 134 � 17 ms (range: 100 to 162 ms),respectively, in the 2 groups were significantly nar-rower compared with paced QRS duration of 167 � 14ms (n ¼ 16; range: 150 to 198 ms; p < 0.05) in patientswith RV septal pacing (unsuccessful HBP).

HB pacing threshold at implantation, 2 weeks,2 months, and last follow-up (19 � 12 months; range:6 to 46 months) was 1.4 � 1.0 V, 1.5 � 1.2 V, 1.7 � 1.0 V,and 1.6 � 1.0 V at 0.5 ms, respectively. The HBPthreshold at last follow-up ranged from 0.5 to 3.75 Vat 0.5 ms. At implantation, pacing thresholds and leadimpedances were similar between the 2 groups(1.3 � 0.7 ms vs. 1.4 � 1.2 V at 0.5 ms and 577 � 132Ohms vs. 565 � 153 Ohms, respectively). SensedR-wave amplitudes were smaller (5.3 � 3.9 mV vs. 6.9� 5.8 mV; p < 0.05) in the AV nodal block groupcompared with infranodal AVB group. HB pacingthresholds, sensing, and lead impedances remained

TABLE 1 Baseline Characteristics

All Patients(N ¼ 100)

AV NodalBlock

(n ¼ 46, 46%)

InfranodalBlock

(n ¼ 54, 54%)

Successful HBP 84 (84%) 43 (93%) 41 (76%)*

Age (yrs) 75 � 12 74 � 13 76 � 9

Male 62 (62%) 29 (63%) 33 (61%)

HTN 70 (70%) 31 (68%) 39 (72%)

DM 32 (32%) 14 (30%) 18 (33%)

CAD 51 (51%) 22 (48%) 29 (54%)

AF 29 (29%) 20 (43%) 9 (17%)*

LVEF (%) 54 � 10 54 � 11 55 � 7

Dual-chamber pacer 82 (82%) 30 (65%) 52 (96%)*

Biventricular pacer 6 (6%) 5 (11%) 1 (2%)

QRSd (ms) 124 � 28 102 � 20 142 � 19*

Normal QRS,RBBB, LBBB

40, 37, 23 38, 6, 2 2, 31, 21

Values are n (%), mean � SD, or n. *p < 0.05.

AF ¼ atrial fibrillation; DM ¼ diabetes mellitus; CAD ¼ coronary artery disease;HTN ¼ hypertension; LBBB ¼ left bundle branch block; LVEF ¼ left ventricularejection fraction; RBBB ¼ right bundle branch block.

TABLE 2 Procedural Characteristics

AV Nodal Block(n ¼ 43)

Infranodal Block(n ¼ 41) p Value

Baseline QRSd (ms) 103 � 20 143 � 18 <0.05

Paced QRSd (ms) 114 � 21 134 � 17 <0.05

S-HBP 19 (44%) 3 (7%) <0.05

NS-HBP 24 (56%) 38 (93%) <0.05

Procedure time (min) 71 � 21 72 � 23 NS

Fluoroscopy time (min) 11 � 8 10 � 4 NS

Values are mean � SD or n (%).

AV ¼ atrioventricular; NS-HBP ¼ nonselective His bundle pacing;S-HBP ¼ selective His bundle pacing.

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stable during the scheduled follow-ups (Table 3). Inpatients with NS-HBP, in addition to HB capture, RVcapture could be demonstrated with mean thresholdsof 0.8 � 0.4 V at 0.5 ms at implant and was stable(1.3 � 0.6 V at 0.5 ms) during follow-up.

A significant increase in HB pacing thresholds orloss of capture occurred in 5 patients (5%) necessi-tating lead revision or replacement, 3 in AV nodalblock, and 2 in infranodal block patients. Threshold

FIGURE 3 Permanent His Bundle Pacing in Advanced Atrioventricul

AV ¼ atrioventricular; HBP ¼ His bundle pacing.

increase or loss of capture occurred within 2 weeks in2 patients and at 2 to 6 months in 3 patients. All5 patients underwent successful repositioning in theHB region. Four patients died during follow-up. Thecause of death was unrelated to the procedure: ma-lignancy in 2 patients, aortic stenosis in 1 patient, andstroke in 1 patient. Heart failure hospitalizationoccurred in 1 patient in the HBP group compared with2 patients in the RV pacing group.

DISCUSSION

In our series, 84% of patients with complete oradvanced AVB, regardless of the location of block,underwent successful permanent HBP. In patientswith AV nodal block, 93% had a successful outcome

ar Block

TABLE 3 Electrical Parameters

Visit

AV Nodal Block Infranodal Block

HBPThreshold, V

R-Wave,mV

ImpedanceOhms

HBPThreshold, V

R-Wave,mV

Impedance,Ohms

Implant 1.3 � 0.7 5.3 � 3.9 577 � 132 1.4 � 1.2 6.9 � 5.8* 565 � 153

2 weeks 1.5 � 0.8 6.7 � 4.6 475 � 111 1.7 � 1.2 9.7 � 7.9* 476 � 121

2 months 1.5 � 0.9 7.2 � 5.5 442 � 109 1.7 � 1.3 9.9 � 8.3* 469 � 81

Last follow-up (19 � 12 months) 1.6 � 0.9 6.4 � 4.4 437 � 75 1.7 � 1.1 9.6 � 9.1* 463 � 78

Values are mean � SD. Pacing threshold tested at 0.5-ms pulse duration. *p < 0.05 versus atrioventricular nodal block.

HBP ¼ His bundle pacing.

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compared with 76% of patients with infranodal AVB.Deshmukh et al. (11), reported success rates of 72%(39/54) in patients with atrial fibrillation undergoingAV node ablation. In a recent series by Kronborg et al.(18), permanent HBP was successful in 85% ofpatients with high-grade AVB and a narrow QRScomplex. They achieved S-HBP in 11% (4 of 38) andNS-HBP in 74% (28 of 38). In our series, S-HBP wasachieved in about one-half of patients with AV nodalblock. We reported a success rate of 75% (15 of 20) inour earlier study consisting of a smaller number ofpatients with complete heart block (16). A highersuccess rate in the present study is attributable toincreased operator experience.

INFRANODAL AVB. HBP can correct chronic bundlebranch block and complete AVB due to infranodaldisease (17,19–28). Longitudinal dissociation of theHB has been suggested to explain this observation(27). Fibers destined to be right and left bundlebranches are differentiated histologically and sepa-rated in the main His trunk (28). Disease in the fibersin the central trunk can cause bundle branch block orcomplete heart block. Pacing adjacent or distal tothese fibers can correct these conduction abnormal-ities. Barba-Picharda et al. (17) studied 182 patientswith AVB (84 with narrow QRS and 98 with wide QRS)and were able to recruit the HB by temporary pacingin 98% (82 of 84) of patients with narrow QRScompared with 52% (51 of 98) of patients with wideQRS. They attempted permanent HBP in only 68% ofthese patients after excluding 32% of patients due tohigh His-bundle pacing thresholds during mapping.Of these 133 patients, permanent HBP was successfulin 59 patients (44%). Considering all patients withheart block, permanent HBP was achieved success-fully in only 32% (44 of 84 in narrow QRS and 15 of98 in wide QRS) of patients. Differences in method-ology and tools used could explain the higher successrates in our study. Compared with a traditional pacinglead with a retractable screw (Tendril 1488 or 1788,

St. Jude Medical, Irvine, California) used by Barba-Picharda et al. (17), we used a dedicated pacing leadwith exposed screw (Medtronic, 3830) deliveredthrough a specially designed sheath with an orthog-onal secondary curve (Medtronic, C315 His).

INTRA-HIS AVB. In 29 of 54 patients (54%) withinfranodal disease, HB could be recruited successfullyby pacing at the site with evidence for HV block on alocal electrogram recorded from the pacing lead sug-gesting that the disease may be discrete (intra-HisAVB) at this level (Figures 2 and 4). In 12 patients(22%), the capture threshold was high, and by posi-tioning the lead slightly more distally, we were ableto recruit the distal HB at lower output (Figure 5). It islikely that the remaining 13 patients (24%) had heartblock due to distal Purkinje system disease (infra-HisAVB), and permanent HBP was unsuccessful. Earlystudies using HB recordings have suggested thatintra-His block contribute to only 15% to 25% of pa-tients with infranodal AVB (21–23). More than 70%was attributed to distal, infra-His AVB. In thesestudies, the diagnosis of intra-His block depended onidentifying split His potentials and/or distal HB po-tential or HV block in the setting of narrow QRS, andhence intra-His block could have been significantlyunderestimated. In our study, split His potentials(Figure 6) were recorded in only 2 patients and narrowQRS was seen in 2 patients. However, our studydemonstrates that in the majority of patients withinfranodal AVB (41 of 54; 76%), the site of conductionblock is localized to the main HB. The postulatedmechanisms for this recruitment of distal His andbundle branches in patients with intra-His block are:1) longitudinal dissociation in the HB with pacingadjacent or distal to the site of delay/block; and/or2) differential source-sink relationships during pacingversus intrinsic impulse propagation; and/or 3) vir-tual electrode polarization effect (29,30). Virtualelectrode polarization is an electrical phenomenon bywhich a stimulus of any polarity creates regions of

FIGURE 4 Intra-HIs AV Block

(A) Discrete intra-His AV block. Twelve-lead electrocardiogram and bipolar electrogram from the permanent His bundle pacing (HBP) (His) lead

in a patient with atrial fibrillation (AF), advanced infranodal AV block, and narrow QRS is shown. (B) Pacing from the HBP lead at 900 ms results

in selective capture of the distal main His bundle and conduction with a narrow QRS. Note the dissociated proximal His bundle potential

recorded from the pacing lead during AF. (C) Atrial pacing after cardioversion at 800 ms results in 2:1 HV block. (D) Pacing from the HBP at

decreasing cycle lengths of 500, 450, and 400 ms results in 1:1 anterograde conduction through the distal His bundle with narrow QRS and 1:1

retrograde conduction to the atrium. This example illustrates the discrete nature of the intra-His AV block and correction by selective His

bundle pacing (S-HBP).

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depolarization and hyperpolarization in the vicinityof the pacing electrode tip, which can result in de-excitation of previously refractory tissue and so pro-vide a pathway for propagation. Virtual electrodepolarization induced by HB pacing may play a role inpromoting propagation in diseased HB tissue.

PROCEDURAL OUTCOMES. Despite not using amapping electrophysiology catheter to locate the HBwe were able to locate the HB using the pacing lead in95 patients (95%). By not using a mapping catheter,we could avoid femoral venous access, as well as theassociated costs and potential risks, withoutincreasing the procedural duration or fluoroscopytimes. Kronborg et al. (18) reported mean total pro-cedural duration and fluoroscopy times of 85 � 31 minand 23 � 13 min, respectively, in their patients with

AV nodal block and narrow QRS complexes, comparedwith 71 � 21 min and 11 � 6 min, respectively, in ourstudy. Zanon et al. (14) reported a fluoroscopy dura-tion of 15 � 9 min and 18 � 13 min for S-HBP andNS-HBP lead placement, respectively, in a series of307 patients. Both studies used the Medtronic 3830pacing lead delivered via a deflectable sheath (Med-tronic C304) and a mapping catheter placed throughthe femoral vein.

QRS DURATION. In patients with AV nodal block,paced QRS duration was only slightly prolongedcompared with baseline (103 � 20 ms vs. 114 � 21 ms).Most patients with NS-HBP had minimal ventricularpre-excitation due to capture of adjacent septalmyocardium in the setting of normal HV intervals. Inpatients with infranodal AVB, baseline QRS was

FIGURE 5 Identifying Distal His Bundle Electrogram in Intra-His Atrioventricular Block

(A) Twelve-lead electrocardiogram of a patient with 2:1 atrioventricular (AV) block and normal QRS. Pacing from the lead at the His bundle

locations shown in the figure results in nonselective His bundle capture with minimal fusion. (B) Intracardiac electrogram from the His bundle

pacing lead at the proximal His bundle location (H1) demonstrates 2:1 HV block. The pacing threshold at this site was 3 V at 0.5 ms. (C) Moving

the pacing lead slightly more distally identifies the distal His electrogram (H2) beyond the site of intra-His block. Pacing threshold at this site

was 1 V at 0.5 ms.

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significantly wider (143 � 18 ms; p < 0.05) than pa-tients with AV nodal block, and paced QRS durationwas slightly narrower (134 � 17 ms) compared withbaseline (p ¼ NS). In a subgroup of patients (n ¼ 7),there was 60 to 80 ms of pre-excitation leading toQRS duration >150 ms, suggesting slow conduction inthe His–Purkinje system despite HB recruitment,allowing for greater degree of RV pre-excitation. It isunclear if these patients would lose HB capture dur-ing long-term follow-up. However, it is important tonote that patients with NS-HBP pacing have signifi-cantly lower RV capture threshold (1.3 � 0.6 V at

0.5 ms in our series) through the same lead serving asRV backup. Baseline QRS duration or morphology wasnot predictive of successful HBP in patients withinfranodal block. RV septal pacing is associated withnarrower QRS than apical pacing but has not beenshown to improve clinical outcomes (8). In a recentcrossover, randomized study of 38 patients, NS-HBP(para-Hisian pacing) was shown to preserve LVfunction and ventricular synchrony compared withRV septal pacing (31). Larger, randomized trialswould be necessary to prove clinical benefits ofpermanent HBP.

FIGURE 6 Intra-His AV Block With Split His Potentials

(A, top panel) The 12-lead electrocardiogram of a patient with second-degree AV block and right bundle branch block with a QRS duration of

140 ms. Electrograms from the His bundle pacing (HBP) lead at implant demonstrated split His (H1 and H2) potentials and Wenckebach

phenomenon in the His. (B) Pacing at 1.5 V at 0.5 ms at this site shows nonselective HBP with QRS duration of 110 ms. (C) Pacing at 1.0 V at

0.5 ms shows three QRS morphologies due to output-dependent capture of RV and His (*), left bundle (#), and right ventricle (/).

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PACING THRESHOLDS. Another important finding inthis study was that the HB pacing thresholds werewithin acceptable range in the majority of patients.The mean HB pacing threshold at implant was 1.4 �0.8 V at 0.5 ms in patients with S-HBP compared with1.3 � 1.0 V at 0.5 ms in NS-HBP. Kronborg et al. (18)reported pacing thresholds of 2.3 � 1.0 V and 1.7 �1.5 V in AV nodal block patients with S-HBP and NS-HBP, respectively. Barba-Picharda et al. (17) reportedacute pacing thresholds of 1.4 � 0.6 V at 1.0 ms and1.9 � 1.2 V at 1.0 ms in patients with AV nodal andinfranodal block, respectively. We believe that themain reason for better pacing thresholds in our serieswas due to the use of C315 His sheath (28). Because ofthe secondary septal curve, this sheath delivers thelead perpendicular to the septal tissue allowing bettercontact. We recently demonstrated that HB injury

current, similar to myocardial injury current, can berecorded in 37% of patients undergoing successfulpermanent HBP and were associated with signifi-cantly lower thresholds (15).

AV NODAL VERSUS INFRANODAL BLOCK. We didnot notice significant differences between the 2groups in the procedural outcomes. However, due tothe unstable nature of the escape rhythm in theinfranodal group, we often placed the atrial lead inthe right ventricle to provide temporary backup pac-ing during HB mapping. Despite advanced AVB, theHB could be located easily in patients with infranodalblock. In patients with AV nodal block, intravenousisuprel may be necessary to increase junctionalescape rates to identify the His electrograms. In pa-tients with AV nodal block and S-HBP, R waves

PERSPECTIVES

COMPETENCY IN MEDICAL KNOWLEDGE:

Permanent HBP is feasible in patients with nodal and

infranodal AVB. The majority of patients with infra-

nodal AVB can be corrected with permanent HBP.

TRANSLATIONAL OUTLOOK: Additional random-

ized studies with long-term follow-up are necessary

to prove clinical benefits of permanent HBP compared

with RV pacing in patients with AVB.

Vijayaraman et al. J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 1 , N O . 6 , 2 0 1 5

His Bundle Pacing in AV Block D E C E M B E R 2 0 1 5 : 5 7 1 – 8 1

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may be <2 mV, requiring adjustment of sensitivitythreshold. Occasionally atrial oversensing may be anissue in this group.

LEAD FAILURE. During a mean follow-up of 19 � 12months, 5 patients required lead revision: 2 had leaddislodgements with intermittent loss of capture, and3 had significant increase in thresholds from 1 to 1.5 Vat implant to 4 to 4.5 V and underwent elective leadrevision (nodal block, 3; infranodal, 2; NS-HBP, 3;S-HBP, 2). Previous studies had described similar orhigher incidence of lead dislodgement in permanentHBP compared with RV pacing.

STUDY LIMITATIONS. The present study describesthe implant success of permanent HBP in patientswith advanced heart block without comparisons ofclinical outcomes with RV pacing. Although HBP maybe superior physiologically to RV pacing and severalsmall studies have shown improvement in LV func-tion and clinical outcomes compared with RV pacing(12,16,31), a randomized trial assessing clinical out-comes (functional status, heart failure hospitaliza-tion, LV function, and echocardiographic parameters)would be necessary to prove superior clinical out-comes. In addition, this study was conducted in ahigh-volume center with extensive experience in HBpacing. Although many of our patients had follow-upof 2 to 3 years, longer term follow-up is necessary toassess the efficacy and safety of HBP, especially inpatients with infranodal disease. Because pacingthresholds with permanent HBP are still higher thanwith a standard RV lead, improvement in lead designs(longer helix), delivery sheaths, and new devices withlonger battery life may be necessary.

CONCLUSIONS

This study demonstrates that permanent HBP pac-ing can be performed safely and successfully in 84%of unselected patients with advanced or completeAVB. Contrary to previous reports, the majority ofinfranodal AVB occurs in the main HB (intra-His)and can be corrected by permanent HBP. The pro-cedure and fluoroscopy duration are less than pre-viously reported and within an acceptable range. Amapping electrophysiology catheter to locate the HBor routine placement of a backup RV lead may notbe necessary.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Pugazhendhi Vijayaraman, Cardiac Electrophysi-ology, Geisinger Wyoming Valley Medical Center,MC 36-10, 1000 East Mountain Boulevard, Wilkes-Barre, Pennsylvania 18711. E-mail: pvijayaraman1@geisinger.edu OR pvijayaraman@gmail.com.

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KEY WORDS complete heart block,His bundle pacing, His Purkinje system,intra-His block