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Abstract
Introduction This study evaluated the feasibility of His bundle pacing (HBP) in consecutive, unselected patients with advanced atrioventricular block (AVB) over a medium-term follow-up period, comparing procedural characteristics between nodal and infranodal sites of the conduction block.
Materials and methods Seventy-five consecutive patients with second-degree or third-degree AVB in which HBP was attempted were prospectively included in this study. The clinical and procedural-related characteristics of the patients were recorded at baseline and over a mid-term follow-up.
Results 72% of the patients had normal QRS duration at baseline. Intracardiac electrograms revealed nodal AVB in 46 patients (61.3%). The permanent HBP procedural success was significantly higher in nodal AVB (84.8%) vs infranodal AVB (31%). There was no statistical difference between paced QRS duration, impedance, pacing and sensing thresholds and fluoroscopy time in the two groups. Infranodal block, baseline QRS duration, left bundle branch block morphology and ejection fraction were significantly associated with HBP procedural failure. The patients were followed for a period of 627.71±160.93 days. There were no significant differences in parameters at follow-up. An increase of >1 V in the His bundle (HB) capture threshold was encountered in one patient with infranodal AVB (11.1 %) and in four patients with nodal AVB (10.25%).
Conclusion Permanent HBP is a feasible pacing technique in nodal AVB with a high success rate and stable thresholds in the medium term. Most infranodal blocks are located within the HB, so there is still the possibility to capture the conduction system, although with lower success rates.
- bradycardia
- pacemaker, artificial
- electrocardiography
Data availability statement
Data are available on reasonable request.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
His bundle pacing is considered the most physiological form of pacing and has proven efficient in patients with advanced atrioventricular block.
WHAT THIS STUDY ADDS
So far, few studies have evaluated the characteristics and correlations between the site of the atrioventricular block (nodal or infranodal) and His bundle pacing procedural success.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The results of this study showed that mapping and pacing the His bundle during physiological pacing for advanced AV block is effective since patients with both nodal and infranodal atrioventricular block may have adequate conduction system capture.
Introduction
Advanced atrioventricular block (AVB) is a common indication for permanent cardiac pacing as the only therapy to reduce morbidity and mortality. A significant percentage of ventricular pacing is expected in these cases since the ventricular is electrically dissociated from the atrium. Several studies have shown that long-term conventional right ventricular myocardial pacing is associated with decreased left ventricular function and that the ventricular pacing burden is an important determinant factor.1 Therefore, physiological pacing has emerged in the last two decades as an alternative for patients with high pacing percentages, having the significant advantage of maintaining ventricular synchrony and preserving left ventricular performance compared with right ventricular pacing.2 His bundle pacing (HBP) was considered the most promising of all the physiological pacing procedures because it reproduces normal biventricular electrical activation.
Unfortunately, HBP has several disadvantages. First, it has a narrow pacing target, limited to the penetrating and branching portion of the His bundle (HB), which theoretically benefits only patients with proximal conduction diseases. Second, several studies have raised concerns about elevated procedural pacing thresholds and the risk of increase over time, and also the possibility of disease progression distal to the pacing site. This situation would make HBP redundant.3
Current physiological cardiac pacing guidelines recommend HBP in patients with AVB, an expected ventricular pacing burden of >40%, and a reduced ejection fraction to prevent further decline in left ventricular function, but there is no mention of different approaches depending on the site of AVB.4
This study aimed to evaluate the feasibility of HBP in consecutive, unselected patients with advanced second-degree or third-degree AVB over a medium-term follow-up period, comparing procedural characteristics between nodal and infranodal sites of the conduction block.
Materials and methods
Study design
This was a prospective, observational, single-centre study.
Patient selection
All consecutive patients with second-degree or third-degree AVB who underwent an attempt at permanent HBP between the 1 January 2020 and 31 December 2021 in the Cardiac Pacing Laboratory of the Brașov County Clinical Emergency Hospital in Romania were added prospectively to our local physiological pacing registry. For this study, the inclusion criteria were the presence of sinus rhythm and a clear HB electrogram identified during the procedure to diagnose the level of block accurately. In the end, 75 patients were included in the analysis.
The baseline demographic and clinical characteristics of the patients were recorded.
Pacing procedure
For the HBP procedure, a C315 His or a C304 His catheter (Medtronic, Minneapolis, Minnesota, USA) and the Select Secure 3830 lead (Medtronic) were used in all patients. The delivery kit was advanced to the anteroseptal tricuspid annulus, and the HB electrogram was identified using unipolar mapping to diagnose the site of the conduction block. Pacing at high amplitudes (5 V at 1 ms pulse duration) was performed to ascertain HB capture, and if that was the case, pacing at decremental amplitudes identified the HB capture threshold. If the pacing threshold was below 2 V at 1 ms pulse duration, the position was accepted and the lead was fixated. If the HB electrogram could not be identified after a maximum of 10 min of fluoroscopy, or the pacing threshold was >2 V, the procedure was abandoned, and left bundle branch area pacing was pursued instead.
We used the following definitions in this study:
(A) A 12-lead ECG with third-degree AVB and a narrow escape rhythm. Bottom tracing shows the intracardiac electrogram recorded from the tip of the HB lead. The atrium (‘A’) is dissociated from the HB (‘H’), suggestive of nodal AVB. (B) A 12-lead ECG recorded during threshold testing in the same patient, showing the transition from non-selective to selective HB capture (black arrow). See text for details. AVB, atrioventricular block; HB, His bundle.
Nodal AVB: atrial electrogram (A) dissociated from the HB and the ventricular electrograms (HV) (figure 1A).
Infranodal AVB: atrial and HB electrograms (AH) dissociated from the ventricular electrogram (V) (figure 2A).
Intra-His AVB: split HB potentials (figure 3A).
Selective HB capture: identical QRS and repolarisation patterns to the baseline morphology and an isoelectric line between the pacing artefact and the beginning of the QRS complex (figures 1B and 2B).
Non-selective HB capture: a ‘pseudo-delta wave’ aspect at the beginning of the paced QRS complex indicative of initial basal myocardial activation and a clear transition in morphology with decremental pacing to either selective HB pacing or pure myocardial capture (figures 1B and 3B).
In patients with baseline bundle branch block: successful HB capture was considered when correction (total or partial) of the bundle branch block occurred, and there was at least a 30% reduction in QRS duration (figures 2B and 3B).5
(A) A 12-lead ECG with third-degree AVB and an escape rhythm with RBBB morphology. Bottom tracing shows the intracardiac electrogram recorded from the tip of the HB lead. The atrium (‘A’) is linked to the HB (‘H’) and dissociated from the ventricle, suggestive of infranodal AVB. (B) A 12-lead ECG recorded during threshold testing in the same patient, showing the transition from non-selective capture of the HB with RBBB correction to selective capture without RBBB correction (black arrow). See text for details. AVB, atrioventricular block; HB, His bundle; RBBB, right bundle branch block.
(A) A 12-lead ECG with intermittent third-degree AVB and a QRS with LBBB morphology. Bottom tracing shows the intracardiac electrogram recorded from the tip of the HB lead. A split HB signal with two components (H1 and H2) is visible, suggesting intra-His AVB. (B) A 12-lead ECG recorded during threshold testing in the same patient, showing the transition from non-selective capture of the HB with LBBB correction (QRS duration of 119 ms) to pure myocardial capture (QRS duration of 159 ms) (black arrow). See text for details. AVB, atrioventricular block; HB, His bundle; LBBB, left bundle branch block.
In successful HBP cases, no ventricular backup leads were implanted. All patients also received an atrial lead. Both leads were connected to a dual-chamber pacemaker.
All procedural-related parameters were recorded.
Follow-up
The patients were followed prospectively in the outpatient clinic at 1, 3 and 6 months after the procedure and every 6 months. Pacing and sensing thresholds were recorded, as well as late complications.
Statistical analysis
Continuous variables were presented as mean±1 SD. Categorical variables were presented as frequencies and percentages. All data were tested for normality of distribution. Statistical comparison of means was performed using the t-test or the Mann-Whitney U test for independent groups and the t-test or Wilcoxon test for dependent groups according to the normality of distribution. Statistical difference between percentages was evaluated using the χ2 test. The association between continuous and dichotomous variables was assessed using binomial logistic regression. A 95% CI was used for all tests. A p<0.05 was considered statistically significant.
Statistical analysis was performed using SPSS software V.26.0 (IBM, Armonk, New York, USA).
Patient and public involvement
Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Results
The mean age of the patients was 70.32±8.22 years, and the majority were males (58.7 %). The main indication for cardiac pacing was a complete AVB. Seventy-two per cent of the patients had normal QRS duration at baseline. All the baseline characteristics, comorbidities and medical treatments of the patients are presented in table 1.
Baseline patient characteristics
Procedural characteristics
During the procedure, intracardiac electrograms revealed nodal AVB in 46 patients (61.3%) and infranodal AVB in 29 patients (38.7%). Three of the 29 patients with infranodal AVB had an intra-His block based on split HB signals. The QRS baseline duration was significantly larger in the infranodal block group. The permanent HBP procedural success was significantly higher in nodal AVB (84.8%) vs infranodal AVB (31%). Selective HB capture was achieved significantly more often in nodal AVB. There was no statistical difference between paced QRS duration, impedance, pacing and sensing thresholds in the two groups. Also, the fluoroscopy and procedural times were similar.
All the procedural characteristics are presented in table 2.
Procedural characteristics
Of note, conduction system capture was visible with very high pacing amplitudes (5 V at 1 ms) in 19 out of the 29 patients (65.5 %) with infranodal AVB, proving that the overall percentage of true infra-His block in our cohort was relatively low (13.3 %).
Binary logistic regression was used to assess the impact of several patient characteristics on permanent HBP outcomes in patients with AVB. The localisation of the AVB below the atrioventricular node was significantly associated with HBP failure, with an OR of 12.38. Also, the baseline QRS duration, left bundle branch block (LBBB) morphology and ejection fraction were significantly associated with HBP procedural failure (table 3).
Logistic regression analysis between patient characteristics and HBP failure
Follow-up
The patients were followed for a period of 627.71±160.93 days. No significant change in paced QRS duration was recorded in patients with successful HBP, regardless of the conduction block level. There were no significant differences between the baseline and follow-up values in both nodal and infranodal groups regarding pacing and sensing thresholds (figure 4). Also, at the last follow-up, there was no significant difference between the nodal and infranodal AVB groups for both pacing thresholds (1.16±0.65 vs 1.33±0.46, p=0.459) and sensing thresholds (3.07±1.26 vs 4.2±1.04, p=0.16). An increase of >1 V in the HB capture threshold was encountered in one patient with infranodal AVB (11.1 %) and four patients with nodal AVB (10.25%). Most circumstances were managed with device reprogramming, except for two in the nodal AVB group, which required reintervention due to premature depletion of the battery. There were no cases of lead dislodgement. In one patient with nodal AVB, the device and lead had to be extracted due to pocket infection, and the system was reimplanted successfully on the contralateral site with adequate HB capture. Also, there was one large postprocedural pericardial effusion, which was drained percutaneous without further recurrences.
Comparison of procedural and follow-up pacing and sensing thresholds in the two groups. AVB, atrioventricular block.
Discussion
The main findings of this study were that: (1) permanent HBP was associated with a high procedural success rate in nodal AVB, (2) infranodal AVB led to a significantly lower success rate and (3) successful HBP in both nodal or infranodal AVB was associated with stable pacing and sensing parameters over medium-term follow-up.
An important benefit of conduction system pacing is the possible localisation of the site of the conduction block during initial mapping, which is not possible during standard right ventricular pacing. If HB mapping reveals dissociated H-V electrograms from the A electrograms, then the site of the block is usually in the atrioventricular node, and permanent HBP makes perfect sense since the conduction system is captured beyond the diseased part. In our study, intranodal AVB had a success rate of 85%, which was in line with the usual success rate reported in large multicentre registries of HBP.6 Conversely, if mapping reveals grouped A-H electrograms dissociated from the V electrograms, the block is labelled infranodal. Still, the exact location is unknown without the extensive septal mapping of the conduction system, which is not feasible in routine practice.
In infranodal blocks, the site of the block could extend from the HB to the distal Purkinje fibres. Nevertheless, existing data stated that a significant proportion of infranodal AVBs are localised within the HB.7 An indirect proof of this could be capturing the distal conduction system by pacing the HB at high amplitudes. Our study made no exception since this was achieved in 65.5% of patients in the infranodal group. Unfortunately, in almost half of these patients, due to unacceptable high capture thresholds, the procedure was abandoned, and so the overall procedural success was lower. In previous studies, a true intra-His site of AVB was encountered in more patients, which could explain the better procedural success rates compared with our research. For example, in observational studies evaluating conduction system pacing in patients with AVB, Vijayaraman et al reported an actual intra-His block in 76%8 and 89%, respectively,7 of the patients with total infranodal AVB. Several mechanisms have been postulated to explain the capture of distal conduction system fibres in intra-His blocks. These include pacing distal to the block site with higher amplitudes, a virtual electrode polarisation effect and a favourable source-sink relationship during pacing.9
As expected, the infranodal group had longer QRS durations and a higher percentage of bundle branch block morphology. As a general rule, in patients with infranodal block, the pacing lead was placed as distally as possible in the HB, closer to the basal myocardium, leading to higher sensing thresholds and a more frequent non-selective pacing response.
An important feature of this study was assessing the association between clinical and electrophysiological parameters and HBP success, with results that may aid in better patient selection and conduction system pacing procedural management. Patients with infranodal blocks were 12 times less likely to achieve successful HBP than those with nodal AVB. Also, patients with baseline wider QRS durations, LBBB morphology and depressed ejection fractions had lower success rates. All the above parameters act as indirect markers of more distal conduction disease. Supporting data were provided by trials investigating the role of HBP in cardiac resynchronisation therapy, which have shown lower success rates compared with the general population.10 Also, in a paper by Upadhyay et al that studied the correction of LBBB with HBP, they found that up to 36% of the patients with LBBB had a distal disease, and the bundle branch conduction abnormality could not be corrected with HBP.11
The pacing thresholds were lower and similar in both groups compared with previous studies.3 Also, there were no differences in the paced QRS duration, fluoroscopy and procedural times. Compared with other HBP studies, lower fluoroscopy times could be explained by the stricter protocol used at our institution and increased operator experience.
An important finding was that both groups’ pacing and sensing threshold parameters were stable over the follow-up period. Previous studies raised concern for a significant increase in the HB capture threshold.12 In our study, this occurred in 5 out of 48 patients (10.4%), significantly lower than reported.3 Fortunately, there were no dislodgements or complete exit blocks, which may have posed a severe problem since we did not use any ventricular backup leads, especially in pacemaker-dependent patients, proving both the stability of the lead and no significant distal progression of the conduction disease.
The novelty of this study was the prospective follow-up over a medium-term of patients with successful HB pacing and AVB, taking into account the site of block. Also, the study occurred in the left bundle branch area pacing era, with more restrictive cut-off points for successful HBP and, thus, closer to the ‘real-life’ practices in electrophysiology laboratories.
The study’s primary limitation is the relatively small number of patients, usually encountered in single-centre studies of conduction system pacing. Another limitation is the lack of exact localisation of infra-His block, which may have explained better the low success rates in these patients. Also, as stated above, with the advent and fast implementation of left bundle branch area pacing, less time was allocated for thorough HB mapping and capture. Otherwise, at the expense of longer procedural and fluoroscopy times, as reported in the earlier studies, some of the failed reported HBP cases may have been successful.
The practical teaching point of this study, when approaching patients with advanced AVB and an intention for conduction system pacing, is that it is worthwhile to spend the first minutes identifying the HB electrogram. If the AVB is nodal, the capture of the HB is achieved with a high success rate. If the AVB is infranodal, a third of the patients can still benefit from HBP with excellent parameters. Otherwise, you have a clear indication and a helpful radiological marker for left bundle branch area pacing.
Conclusions
Permanent HBP is a feasible pacing technique in nodal AVB with a high success rate and stable thresholds in the medium term. Most infranodal blocks are located within the HB, so there is still the possibility to capture the conduction system, although with lower success rates. Therefore, initial localisation of the HB during the cardiac pacing procedure in patients with AVB is essential in choosing the best physiological approach for each patient.
Data availability statement
Data are available on reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
This study was approved by Ethics Committee of the 'Iuliu Hațieganu' University of Medicine and Pharmacy in Cluj-Napoca (number AVZ34/14.02.2022) and the Brasov County Emergency Clinical Hospital (number 30/21.03.2022). The study complied with all aspects of the Declaration of Helsinki. All patients were informed and provided their written consent before the procedure.
Footnotes
Contributors CP: conceptualisation, methodology, data curation, writing—original draft, supervision, writing—review and editing. DP: conceptualisation, methodology, supervision, writing—review and editing. EC, AG, FO: data curation, validation, formal analysis, supervision. CP is the guarantor for this work. All authors agreed to the final version of the submitted manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests CP has received proctorship fees and travel grants from Medtronic.
Patient and public involvement statement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.