Prospective single-center, observational study of patients referred for pacemaker or cardiac resynchronization therapy (CRT) implantation from July 2020 to November 2021. HBP was attempted from July 2020 to April 2021 and LBBAP from May 2021 to November 2021. Patient baseline demographic data and procedural characteristics (procedural success, lead/delivery equipment, fluoroscopy time and dosage, pacing thresholds, sensing, impedance, and programmed stimulation energy) were recorded.

All patients provided written informed consent. The study complied with the Declaration of Helsinki and the study protocol was approved by the institutional ethics committee.

Patients with indication for de novo permanent pacemaker implantation according to the current guidelines were eligible for inclusion in the study.1 Clinical indications for HBP/LBBAP were classified into four categories: (a) intermittent/permanent AV block (including Mobitz type II second-degree AV block and complete heart block); (b) sinus node dysfunction (SND, including tachy-brady syndrome); (c) slowly conducted AF; and (d) CRT. Exclusion criteria included: age <18 years, patients with previous cardiac devices, patients with indication for implantable cardioverter-defibrillator (ICD), and patients with less than three months of follow-up.

All procedures were performed under local anesthesia. In patients under vitamin K antagonists (VKA), anticoagulation was continued in the peri-procedural period with an international normalized ratio within 2.0–2.5 range. In patients taking non-VKA, the last drug dose was omitted.

All electrograms were displayed on an Electrophysiology recording system (EP-TRACER 2 Portable, Schwarzer Cardiotek). An experienced operator was present during all cases.

His bundle pacing procedure

His bundle pacing was performed using the Select Secure model 3830 (Medtronic Inc., Minneapolis) pacing lead delivered through a fixed (C315HIS) or steerable (C304-HIS) (Medtronic Inc., Minneapolis) dedicated delivery sheath as previously described.6,7 Briefly, the delivery sheath was inserted into the right ventricle near the tricuspid annulus over a guidewire through the subclavian vein. The pacing lead was then advanced until the screw was beyond the tip of the catheter. The His bundle electrogram was identified by mapping the atrioventricular septum and subsequently the lead was screwed with clockwise rotations. No backup lead was used. Pacing response was categorized as selective or non-selective HBP according to previously defined criteria.6,7 Selective HBP was considered if: (a) the pacing stimulus to QRS (S-QRS) onset interval was equal to the native His-QRS onset interval (H-QRS); (b) the local ventricular electrogram was not captured by the pacing stimulus, with the stimulus to local ventricular (S-V) activation time on the pacing lead being equal to the His to local ventricular (H-V) activation time (S-V≅H-V) or the difference between the two intervals was less than 10 ms; and (c) the paced QRS morphology was the same as the native QRS morphology (except in cases with correction of the His-Purkinje conduction disease, where the paced QRS is smaller than the native QRS) (Figure 1).6,7 Non-selective HBP was recognized if: (a) S-QRS interval was equal to zero, due to the presence of a pseudo-delta wave, and the stimulus to the end of QRS (S-QRS end) is ≤H-QRS end; (b) the local ventricular electrogram was directly captured by the pacing stimulus; (c) the paced QRS duration was longer than the native QRS duration by the H-QRS interval6,7 (Figure 2).

Figure 1.

Selective His bundle pacing. (A) The 12-lead basal electrocardiogram at 25 mm/s demonstrating complete atrioventricular block, with a QRS 92 ms (inside red bars) and (B) after selective His bundle pacing, showing a paced QRS of 92 ms with the same morphology of native QRS (inside red bars).

(0.55MB).

Figure 2.

Non-selective His bundle pacing. (A) The 12-lead electrocardiogram at 25 mm/s demonstrating the passage from non-selective His bundle pacing (blue) to myocardial capture (green). The pacing stimulus to QRS interval is equal to zero given the presence of a pseudo-delta wave (blue arrow) and paced QRS is wider than native QRS. (B) Demonstration of non-selective His-bundle pacing with a R wave peak time in V6 <100 ms.

(0.6MB).

Left bundle branch area pacing procedure

Left bundle branch area pacing was performed using the Select Secure model 3830 (Medtronic Inc., Minneapolis) pacing lead delivered through the C304-HIS steerable sheath (Medtronic Inc., Minneapolis). The delivery sheath was inserted into the right ventricle near the tricuspid annulus over a guidewire through the subclavian vein. The pacing lead was then advanced until the screw was beyond the tip of the catheter. The His bundle electrogram was first mapped and recorded, and subsequently, the tip of the pacing lead was moved 1.5 cm towards the apex of the right ventricle. In the right anterior oblique 30° position, while pace-mapping at 5 V at 1.0 ms at unipolar pacing, the ideal pacing site was searched according to the presence in lead V1 of a “W” morphology with a mid-notch.8 While screwing in clockwise rotation, the notch migrated towards the end of the QRS wave and the stimulus-to-peak LV activation time (S-LVAT), defined as the duration between the spike and peak of ventricular activation in lead V6, started to decrease their duration. The following criteria were used to confirm capture of the left bundle branch: a paced QRS of right bundle branch conduction delay pattern, and at least one of the next: (a) demonstration of left bundle potential with left bundle-local ventricular electrogram interval of 20–35 ms; (b) demonstration of transition in QRS morphology from nonselective to selective left bundle capture or nonselective to LV septal capture with decrementing output; (c) S-LVAT measured in leads V5–V6 <80 ms; (d) programmed deep septal stimulation to demonstrate refractory period of left bundle9 (Figure 3). If an acceptable His bundle/left bundle capture could not be achieved after 30 minutes, the lead was placed in the mid-septum as confirmed by fluoroscopic views. Programmed stimulation was 5.0 V at 1 ms for HBP and 3.5 V at 0.4 ms for LBBP for safety reasons. After the first month, programmed stimulation was modified according to pacing thresholds.

Figure 3.

Left bundle brunch area pacing with a paced QRS morphology of right bundle branch block pattern and terminal R wave in lead V1, a stimulus-to-peak LV activation time is 76 ms in lead V6. Left bundle branch potential was also visible in the tip of the pacing lead (red arrow).

(1.02MB).

The primary endpoint focused on the feasibility and safety of the physiologic pacing approach. Feasibility was defined as acute success implantation according to the above-described criteria.6–9 Device-related complications were defined as the composite outcome of infection, procedural complications (pneumothorax, pericardial effusion with need for pericardiocentesis, cardiac tamponade, hematoma requiring interventions and thrombotic events), and lead-related complications (repositioning of the lead due to displacement, unsatisfactory threshold rise).

Pacing parameters and clinical outcomes differences between HBP and LBBAP techniques were evaluated perioperatively and at 3-month follow-up.

Statistical analysis was performed using the IBM SPSS Statistics version 20 (IBM, Armonk, New York). Categorical variables are expressed as in frequencies and percentages and continuous variables are expressed as mean±standard deviation or median and interquartile range for variables with and without a normal distribution, respectively. The χ2 test was used to assess for differences between categorical variables and the Student t-test or the Wilcoxon test was used to compare continuous variables with or without normal distribution, respectively. For within-patient changes in parameters, paired t-tests were performed. Statistical significance was accepted for p<0.05.

During the enrolment period, a total of 46 patients fulfilled the inclusion criteria and were included in this study (62% male, mean age of 75±9 years). The main baseline characteristics are described in Table 1. Intraventricular conduction disturbance was present in 27% (n=13) of the patients. Most of the patients (65%) implanted a dual-chamber pacemaker, while 7% (n=3) received a CRT device (all of them had an electrode in the coronary sinus in addition to HBP or LBBAP).

Procedural characteristics are depicted in Table 2. During the HBP procedure, the median HV interval was 50 [43–60] ms, while the median S-LVAT was 80 [76–95] ms for LBBAP.

HBP and LBBAP pacing thresholds, R-wave amplitude and paced QRS duration are depicted in Table 3. In patients with intraventricular conduction delay, there was a reduction in QRS duration after pacing (138±16 ms to 128±20 ms).

Overall, physiologic pacing was attempted in 46 patients. Acute procedural success was achieved in 96% of the cases (44/46 procedures: 21/23 for HBP and 23/23 for LBBAP). Effective HBP was achieved in 91% of the cases (seven patients with selective HBP and 14 patients with non-selective HBP) and in all cases where LBBP was attempted.

No acute complication related to the procedure was reported.

Pacing thresholds remained stable compared to acute thresholds within each group, with exception to R-wave amplitude in the LBBAP that increased significantly at three-months (Table 3). There was no difference between groups concerning paced QRS duration, either at implantation or during follow-up (p=0.54 and p=0.06, respectively).

During the follow-up, need for re-intervention occurred in three patients (6.5%), (due to lead displacement [n=1] or unsatisfactory threshold rise [n=2]). All re-interventions occurred in patients that performed HBP and successful lead repositioning in the His bundle was achieved in all of them.

We acknowledge several limitations in our work. First, this was a nonrandomized, observational study designed to assess the feasibility and safety of physiologic pacing. Second, an experienced operator was present during all cases and therefore our results cannot be extrapolated to other centers. Third, the sample included a relatively small number of patients and therefore the comparison between groups may be underpowered. Clinical outcomes of LBBAP compared to HBP are needed in the future in large randomized clinical trials. Fourth, longer-term follow-up is necessary for the evaluation of clinical outcomes and adverse events. The long-term electrical performance of the lead and potential risks associated with lead extraction are unknown and should be carefully studied.