His bundle pacing versus right ventricular pacing: A comparative study

Abstract

BACKGROUND:

Pacing is the most effective and dependable method for treating complete atrioventricular block (AVB).

OBJECTIVE:

The purpose of this study is to investigate the use of His bundle pacing (HBP) in patients with atrioventricular block.

METHODS:

Patients who underwent HBP or right ventricular pacing (RVP) were enrolled and divided into two groups: the HBP group and the RVP group, respectively. We compared baseline clinical data, fluoroscopy duration, operation duration, pacing electrode parameters during the operation or follow-up, baseline QRS duration, and pacing QRS duration.

RESULTS:

HBP was attempted in 48 patients and was successful in 34 patients who were included in the HBP group. In addition, 30 RVP patients were included in the RVP group. Fluoroscopy duration and operation duration were significantly longer in the HBP group compared to the RVP group. Compared to the RVP group, the HBP group had a higher pacing threshold, a lower R wave amplitude, and a shorter pacing QRS duration. At 6 months of follow-up, the pacing threshold remained higher, the R wave amplitude was significantly lower, and the end-diastolic diameter of the left ventricle was smaller in the HBP group.

CONCLUSION:

HBP was safe and effective for atrioventricular block despite the longer fluoroscopy and operation duration in the HBP group when compared to the RVP group.

Keywords

Atrioventricular block his bundle pacing left ventricular remodeling right ventricular pacing

1. Introduction

Atrioventricular block (AVB) is the most common type of heart block; it is caused by an abnormal extension of the refractory period in a certain part of the atrioventricular conduction, resulting in a delayed atrioventricular conduction velocity [1]. There are three degrees of AVB – a persistent high degree of AVB can indicate a life-threatening organic heart disease [2]. Pacing is the most effective and dependable method for treating complete AVB, and syncope with a high degree of AVB are significant indicators for pacemaker implantation [3]. Right ventricular pacing (RVP), in particular apical pacing, has the benefits of a simple procedure, stable electrode parameters, and rare dislocation. However, long-term dependence on RVP can induce cardiac systolic desynchrony [4, 5], and increase the incidence and mortality rate of atrial fibrillation (AF) and heart failure in patients [6, 7]. The His bundle distal to the AV node is an important cardiac electrical conduction intermediate. Pacing at this site can directly excite the His bundle, achieve normal electrical conduction, and induce the synchronization of the electrical and mechanical activities of the left and right ventricles, resulting in improved clinical outcomes. Currently, this is a hot spot in the field of pacing therapy [8, 9]. The purpose of this study is to investigate the feasibility and safety of His bundle pacing (HBP) in patients with atrioventricular block who require a high percentage of ventricular pacing and its advantages over RVP.

2. Patients and methods

2.1 Study participants

Between May 2014 and August 2017, HBP treatment was attempted for 48 patients at the Internal Medicine-Cardiovascular Department of The Affiliated Chuzhou Hospital of Anhui Medical University. Anhui. Among them, 34 patients were successfully operated on and enrolled in the present study (HBP group). In addition, 30 patients treated with RVP were enrolled in the present study (RVP group). All patients in both groups exhibited atrioventricular block and had indications for pacemaker implantation [10]. All patients provided informed consent.

Before undergoing testing, the basic clinical data, including age, gender, hypertension, diabetes history, NYHA cardiac function classification, and arrhythmia type of the patients were collected. Left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), the ratio of early transmitral flow velocity (E) to the ratio of later transmitral flow velocity (A) (E/A), E to early mitral annular velocity (e’) (E/e’), and left ventricular ejection fraction (LVEF) data were detected via echocardiography.

2.2 Surgical method of HBP

The prefabricated sheath tube (C315 sheath tube; Medtronic Inc., USA) or adjustable sheath tube (C304 sheath tube; Medtronic Inc., USA) was sent to the adjacent area of the diaphragmatic valve of the tricuspid valve in the posterior position via subclavian vein approach, and when necessary, left anterior oblique position 45 ${}^{\circ}$ X-ray fluoroscopy was adopted (Figs 1 and 2). SelectSecure pacing leads (model: 3830, 69 cm; Medtronic Inc., USA) were delivered along the sheath tube, with the distal end of the pacing leads protruding from the head of the sheath tub. The gain was set to 0.1 mV/mm on an electrophysiological recording system (PORTA-I; Sichuan Jinjiang Electronic Science and Technology Co., Ltd., China). The intracardiac ECG was subsequently recorded at a chart speed of 25 mm/s. When the His bundle potential was detected near the atrioventricular septum, an HBP test was performed with a pacing output of 5.0 V/0.5 ms at a rate of 120 times/minute. When it was confirmed that the His bundle was captured by pacing, the threshold was $<$ 2.0 V/0.5 ms, and the H-V conduction was 1:1, the leads were rotated clockwise for 4–6 cycles and fixed. If the pacing electrode was unable to measure the His bundle potential, pacing was initiated at an output of 5.0 V/0.5 ms at a rate of 120 times/minute to identify the S-HBP and NS-HBP pacing sites. If HBP was unsuccessful or the pacing threshold was $<$ 2.0 V, the pacing leads were placed in the RV septum or cardiac apex for routine RVP [11].

Figure 1.

X-ray fluoroscopy images of the His bundle electrode implantation. The prefabricated sheath tube (C315 sheath tube; Medtronic Inc., USA) or adjustable sheath tube (C304 sheath tube; Medtronic Inc., USA) was sent to the adjacent area of the diaphragmatic valve of the tricuspid valve in the posterior position via the subclavian vein approach, and when necessary, the left anterior oblique position 45 ${}^{\circ}$ X-ray fluoroscopy was adopted (Figs 1 and 2). SelectSecure pacing leads (Model: 3830, 69 cm; Medtronic Inc., USA) were delivered along the sheath tube, with the distal end of the pacing leads protruding from the sheath tube’s head. A: The posteroanterior view of the His bundle electrode position; B: The position of the His bundle electrode when it was 45 ${}^{\circ}$ left anterior oblique.

Figure 2.

ECG of S-HBP-treated patients. The gain was set to 0.1 mV/mm on an electrophysiological recording system (PORTA-I; Sichuan Jinjiang Electronic Science and Technology Co., Ltd., China). The intracardiac ECG was subsequently recorded at 25 mm/s. When the His bundle potential was detected near the atrioventricular septum, an HBP test was performed with a pacing output of 5.0 V/0.5 ms at a rate of 120 times/minute. The body surface ECG and intracardiac ECG of a single patient with sinus rhythm and third-degree atrioventricular block are shown. The duration of the QRS wave was 85 ms, and the His-Purkinje system conduction time interval was 42 ms. (B) The His bundle electrode was paced at 1.2 V/0.4 ms, there was an equipotential line between the pacing signal and the beginning part of the body surface QRS wave, S-QRS $=$ 42 ms is equal to the His-Purkinje system conduction time of the patient, and the morphology of the pacing QRS wave is identical to the QRS wave of the patient. (C) The equipotential line between S-QRS disappeared when the His bundle electrode was paced at 5.0 V/0.4 ms, and the QRS wave increased to 120 ms. Figure 2B depicts the S-HBP, whereas Fig. 2C depicts the right ventricle pacing.

Definition and standard of HBP success: This pacing mode is termed selective-HBP (S-HBP) only if it captured the His bundle and not the ventricular muscles surrounding the His bundle. If the His bundle and its surrounding ventricular muscles are captured by pacing, then this pacing mode is termed as NS-HBP [12].

2.3 Observation indexes

Intraoperative pacing thresholds of the HBP and RV electrodes, R wave amplitude and impedance, X-ray fluoroscopy duration, operation duration, and baseline and pacing QRS wave durations were collected.

2.4 Follow-ups

The patients were followed up 6 months later, and the pacemaker control program was used to record data on HBP or right-ventricular electrode, R wave, and the presence of any new AF. The E/A, the E/e’, the LVEF, and the LVEDD were all measured using a color Doppler ultrasound. Additionally, hospitalizations due to heart failure and NYHA heart function grade were tracked.

2.5 Statistical methods

SPSS 20.0 statistical software was used to analyze the data. The data on measurements are expressed as the mean $\pm$ standard deviation (x $\pm$ SD). Count data are expressed in percentage (%). We compared the rates between the two groups using the chi-squared test. $P<$ 0.05 indicated statistical significance.

3. Results

Of the 48 patients studied, 28 had sinus rhythm with a third-degree atrioventricular block, 6 completed S-HBP successfully (Figs 1 and 2), 12 completed NS-HBP successfully (Fig. 3), and 10 underwent RVP after HBP failure. Moreover, 20 patients had persistent AF with bradycardia. Among them, 8 completed S-HBP successfully, 8 completed NS-HBP successfully, and 4 underwent RVP after HBP failure. The reasons for the failure of operation were as follows: the His bundle could not be located in 3 patients, 3 patients had a distal His bundle block (frequency of His bundle ECG $>$ frequency of the V wave), 6 patients had a ventricular electrode pacing threshold of $>$ 2.0 V, and 2 patients were unable to stabilize and the electrode could not be fixed despite multiple attempts. The operation was 70.1% (34/48) successful. These 34 patients whose HBP treatment was ultimately successful were included in the current study as the HBP group. After matching for age and gender, 30 patients who underwent RVP were included in the RVP group in the present study. Among them, 16 patients had sinus rhythm with a third-degree atrioventricular block, and 14 had AF with bradycardia. In addition, 16 of these patients received right ventricular apical pacing, while 14 received right ventricular septal pacing. In contrast to previous studies, spare ventricular electrodes were not implanted in the current study.

Table 1
Comparison of baseline clinical data between the HBP and RVP groups

Baseline indicators	HBP group (34 cases)	RVP group (30 cases)	$P$
Age (year)	70.2 $\pm$ 10.2	69.1 $\pm$ 10.1	0.693
Gender: male	18 (52.9)	17 (56.7)	0.806
Hypertension	23 (67.6)	21 (70)	0.839
Diabetes	7 (20.6)	8 (26.7)	0.567
NYHA heart function grade	1.4 $\pm$ 0.6	1.3 $\pm$ 0.5	0.441
LVESD (mm)	32.4 $\pm$ 3.7	32.2 $\pm$ 3.3	0.810
LVEDD (mm)	49.8 $\pm$ 4.2	50.1 $\pm$ 3.5	0.706
LVEF (%)	55.7 $\pm$ 6.4	55.2 $\pm$ 5.6	0.768
E/A	1.8 $\pm$ 0.3	1.7 $\pm$ 0.3	0.181
E/e’	15.1 $\pm$ 1.9	15.4 $\pm$ 4.1	0.766
AF with bradycardia	16 (47.1)	14 (53.3)	0.975
Sinus rhythm with III ${}^{\circ}$ AVB	18 (52.9)	16 (46.7)	0.975

Note: LVESD: left ventricular end-systolic dimension, LVEDD: left ventricular end-diastolic dimension, LVEF: left ventricular ejection fraction, E/A: the ratio of early transmitral flow velocity (E) to the ratio of later trans mitral flow velocity (A), E/e’: E to early mitral annular velocity (e’), AF: atrial fibrillation, AVB: atrioventricular block.

Figure 3.

ECG of NS-HBP-treated patients. The gain was set to 0.1 mV/mm on an electrophysiological recording system (PORTA-I; Sichuan Jinjiang Electronic Science and Technology Co., Ltd., China). The intracardiac ECG was subsequently recorded at a chart speed of 25 mm/s. When the His bundle potential was detected near the atrioventricular septum, an HBP test was performed with a pacing output of 5.0 V/0.5 ms at a rate of 120 times/minute. The body surface ECG and intracardiac ECG of a patient with intermittent third-degree atrioventricular block are displayed. The QRS wave of the patient lasted 80 ms, hence, the HB potential could not be measured. (B) The His bundle electrode was paced at 5.0 V/0.4 ms, and there was no equipotential line between the pacing signal and the beginning of the body surface QRS wave. However, a similar “ventricular preshock wave” can be observed, the electrical axis of the pacing QRS wave is essentially the same as that of the QRS wave of the patient, and the pacing QRS wave lasted 100 ms. (C) When the His bundle electrode is paced at 1.0 V/0.4 ms, the QRS wave increases to 150 ms. Figure 3B depicts the NS-HBP, whereas Fig. 3C depicts the right ventricular pacing.

The differences in basic clinical data before operation between the two groups including age, gender, hypertension and diabetes history, color Doppler indexes, and the proportion of patients with AF, between the two groups prior to the operation were not statistically significant (Table 1).

Significantly longer intraoperative fluoroscopy and operation times were observed in the HBP group compared to the RVP group (10.6 $\pm$ 3.2 minutes vs. 5.9 $\pm$ 2.4 minutes, $P<$ 0.05; 88.5 $\pm$ 13.5 minutes vs. 72.3 $\pm$ 13.4 minutes, $P<$ 0.05). In addition, there was no statistically significant difference in baseline QRS wave duration between the HBP and RVP groups (97.9 $\pm$ 15.0 ms vs. 98.1 $\pm$ 14.5 ms, $P>$ 0.05). The ventricular electrode threshold was significantly higher in the HBP group than in the RVP group (1.3 $\pm$ 0.3 V vs. 0.8 $\pm$ 0.2 V). Significantly less R wave amplitude was detected at the ventricular electrode in the HBP group than in the RVP group (7 $\pm$ 4.0 mV vs. 12.1 $\pm$ 4.2 mV). The QRS wave pacing duration in the HBP group was significantly shorter than in the RVP group (112.1 $\pm$ 17.8 ms vs. 153.9 $\pm$ 9.9; Table 2).

Table 2

Comparison of indicators during the operation and follow-ups after the operation between the HBP and RVP groups

Main outcome measures	HBP group (34 cases)	RVP group (30 cases)	$P$
Intraoperative
Baseline QRS wave duration (ms)	97.9 $\pm$ 15.0	98.1 $\pm$ 14.5	0.952
QRS wave pacing duration (ms)	112.1 $\pm$ 17.8	153.9 $\pm$ 9.9	0.000
Perspective time (min)	10.6 $\pm$ 3.2	5.9 $\pm$ 2.4	0.000
Operation time (min)	88.5 $\pm$ 13.5	72.3 $\pm$ 13.4	0.000
Ventricular electrode impedance ( $\Omega$ )	687.9 $\pm$ 171.4	676.7 $\pm$ 151.8	0.784
Amplitude of R wave (mv)	7.0 $\pm$ 4.0	12.1 $\pm$ 4.2	0.000
Ventricular electrode pacing threshold (V)	1.3 $\pm$ 0.3	0.8 $\pm$ 0.2	0.000
Half year follow up
Ventricular electrode impedance ( $\Omega$ )	656.9 $\pm$ 151.2	663.2 $\pm$ 141.5	0.736
Amplitude of R wave (mv)	7.4 $\pm$ 4.5	13.4 $\pm$ 5.0	0.000
Ventricular electrode pacing threshold (V)	1.4 $\pm$ 0.3	0.8 $\pm$ 0.3	0.000
Ventricular pacing ratio $>$ 40%	33 (97.1)	27 (93.3)	0.596
NYHA heart function grade	1.5 $\pm$ 0.5	1.4 $\pm$ 0.4	0.483
LVESD (mm)	30.6 $\pm$ 2.7	32.0 $\pm$ 3.0	0.052
LVEDD (mm)	49.6 $\pm$ 4.7	52.3 $\pm$ 5.2	0.040
LVEF (%)	55.0 $\pm$ 5.8	54.7 $\pm$ 6.2	0.543
E/A	1.9 $\pm$ 0.4	1.8 $\pm$ 0.2	0.060
E/e’	13.0 $\pm$ 2.3	14.7 $\pm$ 4.6	0.078
New cases of AF	1/18 (5.6)	2/16 (12.5)	0.915
Heart failure requiring hospitalization	0	2 (6.7)	0.216

Program control of the pacemaker was performed during follow-ups within 6 months of the operation, and there was no statistically significant difference between the HBP and RVP groups in the proportion of patients with a ventricular pacing percentage of $>$ 40% (97.1% vs. 93.3%, $P=$ 0.596). In addition, the difference in ventricular electrode impedance between the HBP and RVP groups was not statistically significant (656.9 $\pm$ 151.2 vs. 663.2 $\pm$ 141.5), and the ventricular pacing electrode threshold was greater in the HBP group than in the RVP group (1.4 $\pm$ 0.3 vs. 0.8 $\pm$ 0.3, $P<$ 0.05). In the HBP group, one patient’s pacing threshold increased from 2.0 V to 2.5 V prior to surgery, no obvious electrode translocation was observed by imaging, and the threshold remained stable after multiple times of program control. In addition, the amplitude of the R wave at the ventricular electrode was significantly reduced in the HBP group compared to the RVP group (7.4 $\pm$ 4.5 vs. 13.4 $\pm$ 5.0, $P<$ 0.05). LVEDD was larger in the RVP group compared to the HBP group, as determined by color Doppler ultrasound (52.3 $\pm$ 5.2 mm vs. 49.6 $\pm$ 4.7 mm). Furthermore, the differences between the two groups in LVEF, NYHA cardiac function grade, incidences of new AF, and heart failure hospitalization rate were not statistically significant (Table 2). No electrode-related complications were found in either group.

4. Discussion

According to previous research, the success rate of HBP ranges from 44% to 95% depending on the materials of the implanted electrodes and the characteristics of the selected patients. Electrophysiological mapping catheter implantation for His bundle and backup RV electrode are no longer required on a routine basis thanks to the development of surgical procedures and the progress of clinical research [13, 14, 15]. This simplifies the surgical procedures, and saves medical costs.

HBP technology was developed recently – there are few relevant studies and its indications are not clearly outlined in pertinent guidelines. According to a previous study, there is no single “sweet spot” for optimal ventricular pacing, and the optimal implant sites vary [16]. Unlike conventional right ventricular apex or septal pacing, HBP simultaneously excites the left and right bundle branches, and the QRS wave it generates is noticeably narrower than that of RVP. This is an important indication of ventricular synchronization. Favorable hemodynamic effects can be observed immediately after a successful pacing. HBP is a type of physiological pacing that can reduce complications caused by RVP dependence, as seen in long-term observation [17, 18]. High atrioventricular block, AF with a slow ventricular rate, and AF with atrioventricular node ablation due to inability to control the ventricular rate are the ideal indications for high blood pressure. Slow arrhythmia that necessitates a high proportion of ventricular pacing is the key characteristic. Kronborg et al. conducted a prospective, randomized, double-blind, and crossover trial; in the one-year follow-up of some narrow QRS wave patients with atrioventricular block and an LVEF of $>$ 40%, HBP could preserve LVEF and mechanical synchronization compared with right ventricular septal pacing [19]. In a study, patients with AF underwent NS-HBP after atrioventricular node ablation, and the results indicated that NS-HBP was reliable. It was also significantly superior to RVP in terms of NYHA functional classification, six-minute walking distance, cardiopulmonary function, and oxygen consumption [20]. Compared with right ventricular apical pacing, the rate of re-hospitalization due to heart failure was significantly lower in the HBP group than in the RVP group, as reported by Parikshit et al., in patients with the percentage of ventricular pacing $>$ 40% [16]. A long-term follow-up by Abdelrahman et al. revealed that HBP significantly reduced mortality, the rate of hospitalization due to heart failure, and the incidence of major endpoint events, such as the need to upgrade biventricular pacing [21]. In particular, the significance of these benefits increased when the percentage of ventricular pacing was $>$ 20%. In the present study, we selected atrioventricular block patients with indications for permanent pacemaker implantation, including patients with sinus rhythm and third-degree atrioventricular block and AF patients with bradycardia. The duration of the QRS wave was significantly shorter in the HBP group compared to the RVP group. Moreover, the program control of the pacemaker during follow-up revealed that the proportion of ventricular pacing in the vast majority of patients in these two groups was $>$ 40%, similar to the findings of previous studies [16, 17, 18, 19, 20, 21]. In the follow-ups, the difference in NYHA heart function grade, rate of hospitalization due to heart failure, and the incidence of new AF between the two groups was not statistically significant, which is similar to the results of previous studies [16, 17, 18, 19, 20, 21]. However, the LVEDD in the RVP group was significantly greater than in the HBP group. This suggests that HBP has a protective effect against remodeling of the left ventricle caused by a high RVP ratio.

In addition to its effect in treating bradycardia, the scope of HBP application has expanded to a certain extent. Daniel et al. demonstrated that in patients with heart failure and a wide QRS wave, HBP could correct the bundle-branch heart block, shorten the duration of the QRS wave, and significantly improve the life score, NYHA heart function, and six-minute walking distance [22]. Additionally, its curative effect was equivalent to biventricular pacing. Peiren et al. even reported that after HBP, the NYHA heart function was significantly enhanced, LVEDD was significantly decreased, and LVEF was significantly enhanced in patients with AF and atrioventricular block ablation who did not respond to cardiac resynchronization therapy (CRT) [23].

HBP is a pacing mode that permits the patient to be in a physiological state, but it has certain limitations. The top of the electrode is parallel to the atrioventricular septum due to the unique location of the His bundle [24]. The electrode approaches the upper portion of the valvular ring at a fixed angle with the tissue [25]. Therefore, it is extremely challenging to operate the catheter to detect the His bundle and fix electrodes, which increases the duration of the operation [26]. In the present study, the durations of the intraoperative fluoroscopy and the operation were significantly longer in the HBP group than in the RVP group. In addition, the His bundle could not be detected in three patients and the electrodes could not be fixed in two patients, resulting in operation failure. This indicates that the operation of HBP is complicated. Frequently, the success or failure of HBP is determined by the blocking site of the His-Purkinje system. In the present study, the distal His bundle block resulted in the failed operations for three patients. His bundle is a fibrous structure located in the center of the heart, and contains few myocardial tissues. Therefore, the majority of electrodes implanted in this location have a low R wave, a high threshold, and poor fixation. In the present study, the R wave of ventricular electrodes was significantly lower, and the threshold was significantly higher in the HBP group compared to the RVP group. In addition, six patients had an intraoperative threshold of $>$ 2 V. HBP was discontinued to prevent premature battery depletion caused by the high threshold and potential future loss of pacing capture. Despite a six-month follow-up after the operation, there was no significant increase in threshold or dislocation of electrodes in the HBP group. Hence, it remains necessary to strengthen the follow-up observation.

Main limitations: There are numerous limitations to this study. This was not a randomized controlled trial in the first place. Second, this study was limited by its single-center design and small sample size. Thirdly, subgroup analyses of selected His and non-selected His and apical and septal His were not conducted. Consequently, further subgroup analysis should be conducted in the future.

5. Conclusion

Despite the longer fluoroscopy and operation duration in the HBP group compared to the RVP group, HBP is safe and effective for atrioventricular block.

Funding

The study was financially supported by the Anhui Province Science and Technology Key Project (ID: 1501041163).

Competing interests

The authors declare that they have no competing interests.

Footnotes

Acknowledgments

We are particularly grateful to everyone who helped with the article.

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His bundle pacing versus right ventricular pacing: A comparative study

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Patients and methods

2.1 Study participants

2.2 Surgical method of HBP

2.4 Follow-ups

2.5 Statistical methods

3. Results

Table 1 Comparison of baseline clinical data between the HBP and RVP groups

5. Conclusion

Funding

Competing interests

Footnotes

Acknowledgments

References

Table 1
Comparison of baseline clinical data between the HBP and RVP groups