Physiological pacing—imitating the normal cardiac conduction pathway—has long been put forward as a means of restoring atrioventricular synchrony. This concept has been historically redefined since the first His-bundle pacing attempt to achieve ventricular synchrony in 2000 (1). Thereafter, a growing body of evidence shows the efficacy of His-bundle pacing (2, 3). However, most studies utilize advanced pacemakers for a limited population (4–6), which cannot be generalized to patients requiring a more cost-effective therapy. In addition, early battery depletion often occurred as a result of the elevated pacing threshold, impeding the application of His-bundle pacing (7). Su et al. optimized the technique by pacing at the distal His-bundle or even closer to the left bundle branch (LBB), presenting a narrow QRS with steady pacing parameters (8). Furthermore, in 2017 they reported the first case of LBB pacing (LBBP) that safely corrected the LBB block in a heart failure patient and showed steady pacing parameters during follow-up (9). Based on current evidence, LBBP seems to be a safe and effective alternative to conventional pacing (10–12).

As the conductive pathway degenerates, aged patients had a higher incidence of symptomatic bradycardia, which can only be corrected by implantation of a pacemaker. Nevertheless, elderly patients have distinctive features compared with the general population: more tortuous veins, lower BMI, and lower cardiac mass (13). These differences increase the potential risks of the implantation procedure. Additionally, comorbidities like hypertension, ischemic heart disease, and chronic renal disease (14) are pervasive in the elderly population, which could further worsen the prognosis for pacemaker implantation. Although, LBBP is a promising approach, inevitable transseptal lead fixation and mapping of His and LBB potential would presumably pose a higher risk for complications. To our knowledge, no current study has investigated the feasibility and safety of LBBP specifically in an advanced age population.

Therefore, our multicenter comparative study was designed to observe the feasibility and safety of LBBP in patients over age 80 compared to younger patients.

Our multicenter comparative study compared the profiles of 159 elderly patients aged over 80 with 182 younger patients with symptomatic bradycardia who underwent LBBP. Our findings suggest that physiological pacing via LBBP can be performed in elderly patients without increasing the risk of complications and that midterm prognosis of elderly patients undergoing LBBP was comparable with the younger patient group.

Population aging is a major issue, with one report estimating over 150 million Chinese citizens will be over 80 by 2050 (19). Elderly patients should be considered as a special community, as they have more co-morbidities and worse prognosis. Especially in the consideration of pacemaker implantation, elderly patients had more tortuous veins, lower BMI, and lower cardiac mass, which accounts for the higher risk of complications such as pneumothorax, lead dislodgement, perforation, and loss of capture (20). Therefore, investigating the safety and prognosis of pacemaker implantation in the advanced aged population is of great importance.

LBBP is a novel and feasible pacing maneuver to achieve physiological pacing. LBBP requires the capture of left bundle branch potential to mimic the normal electric conduction. In our multicenter study, LBB potential is recorded in 54.3% of the population, and 58.9% of the younger group and 50.0% of the elderly group, respectively. The capture of left conduction system could be hard, as most studies on LBBP reported that the ratio of LBB potential capture ranged between 50 and 80% (3, 12, 21, 22). An animal study has confirmed that positioning the lead deep enough to the left septal subendomyocardium could easily capture the left conduction system (23). Therefore, based on our findings, we believe that in most situations the capture of the left conduction system is mostly dependent on lead manipulation rather than age and condition of patients. Besides, several clinical evidences validated that LBBP could be achieved safely (3, 10, 12, 24). However, most studies have failed to evaluate the efficacy in the advanced elderly population. In our evaluation of safety, through a follow-up of 20.0 ± 6.1 months, the incidence of overall safety events was low in both groups and similar to that of previous studies (21). Among complications related to LBBP, lead-related complications rarely occur. Chen et al. reported two complications in 612 patients (24) and Su et al. reported two cases of lead dislodgement in 632 patients (10), which are similar to the incidence in our study. Since Huang et al. (16) published and standardized the LBBP maneuver and criteria (18), complications like lead dislodgement have been rarely reported in an experienced center.

Specifically, elderly patients undergoing LBBP were at a higher risk of perforation and should be independently considered. One previous study has shown that ventricular perforation is correlated with several factors during conventional pacing, including the use of temporary pacemakers, use of steroids, use of helical screw leads, BMI of <20, and old age (13). Most importantly, their study indicates that a thinning of the cardiac wall in the elderly population and excessive leads in the RV were the major risk factors contributing to perforation. In the consideration of LBBP, multiple leads were routinely used including one or two active fixation 3,830 leads and sometimes temporary pacing lead, which could presumably pose a higher risk of complication, especially when LBBP was performed in the elderly population. In the present study, four out of five cases of periprocedural pericardial effusion occurred in the elderly group and one case of cardiac tamponade occurred requiring pericardiocentesis, which failed to reach a statistical significance. Compared with previous studies on LBB and His-bundle pacing, the incidence of perforation ranged from 0 to 3%, (10, 12, 24) which was relatively low and comparable with ours.

Collectively, we believe the overall safety of LBBP in the elderly is acceptable in an experienced center. However, we acknowledge that the incidence of complications was still too low to detect the significance; larger scaled studies are warranted to provide stronger evidence on safety in the elderly population. Based on our experience, LBBP should be performed with extra caution in patients with advanced age, while assessment of lead depth by angiography could help prevent perforation. We recommend assessment of lead depth with the following criteria: (1) Unipolar pacing impedance at the distal tip should be > 500 ohms (sharp decrement indicates perforation into LV); (2) Once LBB potential has been recorded and pacing parameters are acceptable, screwing should be immediately stopped; and (3) Under DSA, we judged lead depth by continuously injecting contrast (Figures 1D–F). In addition, when retracting the delivery sheath, a rebound of the distal portion of the lead should be monitored to confirm stable fixation (16).

Last but not least, the benefits of LBBP in patients over the age of 80 was also comparable with the younger population. LBBP could achieve physiological conduction, mechanical synchrony, and correct LBB block (3, 6, 25, 26), and presumably could improve the outcomes of patients with bradycardia. Our multicenter study showed that LBBP in elderly patients could indeed achieve comparable shortening of QRS duration and improvement of cardiac function with the younger group, and such results were in accord with the previous published studies (3, 12, 26). However, although, not statistically significant, there was a tendency of higher incidence of MACE in the elderly group including acute myocardial infarction and cerebral infarction. We believe such a tendency resulted from the high rate of comorbidities in the elderly population. Therefore, we believe that LBBP could correct bradycardia with better electrical and mechanical synchrony in elderly patients, but the benefits should not be overestimated.

Our results should be interpreted with caution. First, our results cannot be extrapolated to patients who undergo pacemaker implant for reasons other than symptomatic bradycardia. Second, we aimed to compare the performance of LBBP between two age groups, while a comparison of LBBP with conventional RV pacing in the elderly population could better validate the benefits and risks of LBBP. Well-designed, large-scaled, comparative studies are required to further illustrate the safety and efficacy of LBBP in the elderly population. In addition, although, the sample size was considerable and the follow-up period was over 1 year, it was still too short to detect a late difference between groups. Studies of a larger scale and with longer follow-up periods are necessary to validate the long-term safety and benefits of LBBP.

Compared to the younger group, LBBP could be achieved in patients over 80 years old with symptomatic bradycardia, and comparable mid-term safety and prognosis can be observed. Long-term safety and benefits of LBBP still require further evaluation.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by ethics committee of Shanghai Tenth People's Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

DZ, XC, and SW contributed to the interpretation of data for the work. ZR and BC contributed to drafting the work. PJ, YC, JuZ, JiZ, HY, and XL contributed to the acquisition of data. RG, HL, and JX contributed to the analysis and revision of the work. DZ, XC, and YX contributed to the conception of the work. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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