Transcatheter aortic valve replacement (TAVR) has been proved effective and has been becoming a solid therapeutic alternative for high-risk patients with severe aortic stenosis (AS). Nowadays, it is also considered for patients with intermediate risk even lower risk patients in certain situations [1, 2]. However, conduction abnormalities remain the major complications of this procedure. Conduction disturbances in this setting mainly include complete atrioventricular block (AVB) and new onset left bundle branch block (LBBB), which partly offset the benefit of this remarkable technology. The mechanism of conduction abnormalities following TAVR may be explained by the close anatomical relationship between the implantation site of the aortic artificial valve and the conduction system, with the incidence varying among different implantation techniques and the morphology of the artificial valve used [3, 4]. These complications limit the application of TAVR in patients who are younger or at low-risk for surgical operations [1, 5]. The incidence of complete AVB following TAVR is well described and permanent pacemaker implantation (PPI) is recommended as a remedy. However, the reported incidence of new onset LBBB following TAVR has a substantial variation. For new onset LBBB, controversy remains regarding the definition, cause, incidence, and its effect on cardiac function. The optimal strategy for new onset LBBB in this population has not been clearly established yet. Cardiac resynchronization therapy (CRT) has been proven to improve clinical outcomes in patients with left ventricular dyssynchrony. Recently, His bundle pacing (HBP) and left bundle branch pacing (LBBP), also known as His-purkinje conduction system pacing (HPCSP), have been introduced as an alternative modality of physiological pacing to achieve electrical synchrony of the left ventricle [6]. HPCSP can capture His bundle region or left bundle branch directly and make the excitation pass down along the physiological pathway, which is a more physiological pacing mode. Researchers have reported the feasibility and safety of HPCSP. Increasingly more research is focusing on HPCSP in post-TAVR patients, including its effect on cardiac function and mortality of TAVR related new onset LBBB. For the special population of postoperative LBBB in TAVR, further studies are needed to illustrate the pathophysiological basis of postprocedural conduction block, factors influencing its outcome, the optimal timing of pacing therapy, and the impact of physiological pacing techniques on the prognosis of these patients.

The anatomical relationship between the aortic artificial valve and the cardiac conduction system is the basis of postoperative conduction abnormalities in TAVR. His bundle is close to the aortic valve when it crosses the central fibrous body and reaches the interventricular septal membrane, and the left bundle branch is close to the bottom of the fibrous triangle between the non-coronary sinus valve and the right coronary valve. Direct mechanic injury, including edema, inflammation, and ischemia, may occur during the insertion of the guide wire, balloon dilation, and valve implantation [7, 8, 9, 10]. In addition, the following factors may affect the occurrence of LBBB: (a) Baseline features of the patients: such as preexisted conduction abnormalities and aortic valve calcification increase the incidence of conduction block after TAVR [11, 12]; (b) Procedural factors, the membranous interventricular septum length and the implantation depth considering the membranous septum length is an important factor regarding the development of LBBB or AVB. The risk of LBBB increased by 15% to 40% for each 1 mm further in depth of valve implantation [13]. Currently, the recommended depth of valve implantation is less than 6 mm; (c) Device-related factors: the novel transmission conduction delay is also affected by the type and size of the prosthesis. The self-expanding valve system such as Medtronic CoreValve will expand further after implantation, exerting a higher radial force on left ventricular outflow tract (LVOT) and resulting in higher risk of conduction block [10, 14].

Some of the above factors have been proven to be predictors of new conduction block after TAVR, with the prosthesis implantation depth the most relevant risk factor. Other risk factors including the type of valve implanted, overexpansion of native annulus, the occurrence of right bundle branch block (RBBB) at baseline, preexisting LVOT calcification, preexisting first-degree AVB and prolonged baseline QRS duration, previous coronary bypass and female gender [15, 16, 17]. The presence of RBBB at baseline was one of the important predictors. Studies have reported significantly higher rate of PPI in patients with preoperative RBBB. Because most of the study end points were identified as new LBBB after TAVR, patients with baseline LBBB were excluded at enrollment, so there are few studies on the association between baseline LBBB and new block. According to the literature review, Mangieri proposed that ventricular depth of the prosthesis (odds ratio [OR] = 1.37 for each increase of 1 mm) and baseline QRS duration (OR = 1.24 for each increase of 4 ms) could be used as predictors of new onset persistent LBBB. No data existed regarding predictors of transient LBBB [18].

The incidence of PPI was lower in surgical aortic valve replacement (3.2%) than in TAVR [5]. Rates of PPI after TAVR range between 3.4% and 25.9% according to the European Society of Cardiology (ESC) guidelines for 2021. New-onset LBBB is the most common conduction block following TAVR, with the incidence of 4%–65% [10, 14]. Muntané-Carol G analyzed the incidence of LBBB in different valve systems [19]. Due to improvements in structure and materials, the new generation of valve systems has greatly improved the safety of surgery, but the impact on the conduction system has not been significantly improved. So far, the incidence of LBBB in the new generation of valves reported in the literature is as high as 77% [20]. The great variation of incidence is most likely attributed to differences in inclusion electrocardiogram criteria and valve types. Studies reported that incidence of new onset LBBB following the CoreValve prosthesis implantation was higher than the Edwards SAPIEN prosthesis [14]. Another important reason is whether or not the strict diagnostic criteria of LBBB have been adapted in these studies was not specifically addressed. However, no study up until now has evaluated the incidence of LBBB post-TAVR with strict criteria and therefore it is highly possible that from where the bias was derived. Alqarawi et al. [21] described the Electrocardiograph (ECG) characteristics of new onset LBBB following TAVR and proposed a new ECG definition of LBBB which consists of two novel criteria: notching/slurring of the R wave in at least one lateral lead and an R wave $\le$20 ms in V1. A recent Expert Panel suggested that patients with unresolved new onset LBBB on day 2 post-TAVR, which defined as QRS duration $>$150 ms or PR interval $>$240 ms, could be considered for PPI.

Approximately 90% of TAVR related new onset LBBB occurs within 24 h and may be associated with mechanical damage caused by the guide system [22]. The damage may be temporary, some new onset LBBB can recover within hours or days. About 55% of new onset LBBB will persist at hospital discharge. However, nearly 60% of them will persist after discharge. Late-onset LBBB is very rare [23].

High degree of AVB after TAVR usually predicts a poor prognosis, resulting in deterioration of cardiac function and a high mortality. However, patients with new onset LBBB often have insidious clinical symptoms and weak intervention indications, while existing prognostic studies mainly include these patients, so the impact of TAVR related new onset LBBB on cardiac function and mortality is also controversial [24].

Based on all the previous studies, current available data do not recommend a prophylactic pacemaker implantation in patients with TAVR related LBBB. However, pacemaker implantation is recommended in presence of complete AVB. American College of Cardiology updated a guideline in 2020 in which a PPI was recommended in high-degree AVB, and AVB patients at high risk of developing to LBBB, which defined as prolongation of QRS or PR interval $>$20 ms, or QRS duration $\ge$150 ms or PR interval $\ge$240 ms after TAVR. Whereas the guidelines do not recommend PPI in patients with isolated new onset LBBB after TAVR [34].

There are three questions still needed to be answered to provide the appropriate management of the patients with LBBB after TAVR.

5.3 What Type of Pacing Method Should Be Performed?

Traditional RVP can prevent some cases of AVB, but it may weaken the improvement of cardiac function brought by TAVR and lead to ventricular systolic asynchrony. RVP does not provide benefit in patients with LBBB after TAVR. Pacing method should be selected as prudent as possible. LBBB related LV dysfunction, biventricular pacing (Traditional CRTP/D [Cardiac resynchronization therapy/Cardiac resynchronization therapy-cardioverter-defibrillator]) may represent an interesting option in this setting. Furthermore, resynchronization therapy should also be considered in patients with high degree AVB, high percentage (predictable $>$40%) of ventricular pacing, and reduced LVEF (50%) and with sufficient life expectancy. Nowadays, researches have shown the benefit of biventricular pacing in patients with low LVEF and persistent LBBB after TAVR. In addition to the improvement of LVEF, biventricular pacing seems to be effective in decreasing hospitalizations in heart failure patients. However, most patients undergoing TAVR implantation have preserved LVEF. There has been no previous study on the efficacy of CRT in this population. Therefore, patients with LBBB and cardiac dysfunction are the main target population for biventricular pacing to correct electrical asynchrony. CRTP/D can be systematically implanted in such patients to prevent heart failure promoted by RVP or LBBB electrical activation. But this population did not truly reveal the benefit of CRTP/D in LBBB related heart failure after TAVR. More importantly, TAVR procedure is expensive enough in most countries and regions, CRTP/D will further increase the financial burden of patients.

Nowadays, HPCSP is booming around the world, the anatomy of the conduction system and the most frequently used lead location site of HPCSP are shown in Fig. 1. It can directly capture His bundle or left bundle branch, which is a more physiological pacing mode [51, 52, 53]. As the advent of new tools and technologies greatly facilitated HPCSP implantation, a growing number of researchers are coming to a consensus that HPCSP is a more physiological approach than other existing pacing model, especially in patients with LBBB in combination with heart failure or with high percentage of expected pacing needs [54, 55, 56, 57]. It is now generally accepted that HPCSP includes two pacing modalities, HBP and LBBP, the main difference between them is the anatomical location of the pacing lead [58, 59]. Nonetheless, both of them can capture the conduction system. In the setting of patients with AVB, HBP and LBBP were both successful in achieving stable and low capture thresholds. Although thresholds of HBP upon implantation were higher compared to LBBP (1.2 $\pm$ 0.7 V vs 0.6 $\pm$ 0.3 V; p 0.001), both remained stable during follow-up [53].

Fig. 1.

Diagram of His-purkinje conduction system pacing. Anatomical localization of HPCSP leads. For LBBP, the pacing lead is delivered transvenously into the right ventricle through C315 His-sheath and screwed into the IVS (LBB region). While HBP lead is implanted at His-bundle or distal His bundle (His bundle area). HPCSP, His-purkinje conduction system pacing; LBBP, left bundle branch pacing; IVS, interventricular septum; LBB, left bundle branch.

5.3.1 HBP

In 2000, Deshmukh [60] first described permanent HBP combined with AV node ablation in patients with AF and LV systolic dysfunction. From an electrical and hemodynamic point of view, his bundle is the ideal site for physiological pacing. Current evidence shows that HBP is safe and effective and feasible in practice in these settings. Researchers using HBP, instead of RV pacing, biventricular pacing, or His-optimized CRT (HOT-CRT), which achieves a synergistic effect to improve synchrony [50]. With the accumulation of safety and efficacy data, HBP is likely to play a growing role in pacing therapy in the future. However, the technical challenge and problem with elevated long-term thresholds in LBBB patients had been obstacles to application in routine clinical practice.

5.3.2 LBBP

Left bundle branch pacing (LBBP) was first reported by Huang in 2017, according to Huang, LBBP avoids further deterioration of the proximal His bundle or AV node due to delayed progression of AV conduction, and also provides more space for AV nodal ablation [61]. LBBP generates a narrow paced QRS duration and fast LV activation time as HBP and the site of LBBP lead bypasses the vulnerable region which was more distal and deeper, makes it easier to fix. As an alternative physiological pacing therapy for HBP, LBBP has a benefit that avoids many of the limitations of HBP or RV pacing [62]. Compared to HBP, LBBP has a lower and more stable capture threshold because the pacing site is located in the ventricular septal tissue, improving long-term safety and the device longevity. Besides, LBBP technique is relatively simpler than HBP which makes it easier to learn and promotion, because of wide spread of fascicules of left bundle branch in the sub-endocardium of the left side of the interventricular septum (IVS).

5.3.3 HPCSP in TAVR Related LBBB

For the special population of new onset LBBB after TAVR, according to etiological mechanism, the electrical dyssynchrony is caused by direct conduction injury. If irreversible mechanical dyssynchrony eventually occurs, it may be an ideal indication for HPCSP [63, 64, 65, 66, 67]. In 2018, Sen J et al. [63] reported the first case of LBBB in the setting of TAVR corrected by pacing at the His bundle. Then, De Pooter reported the inspiring results of a prospective, multi-center study regarding the feasibility and safety of HBP to correct a TAVR-induced LBBB, though the study included only 16 patients [64]. In the post-TAVR LBBB setting, the correction of LBBB by HBP usually requires a higher pacing output, which depends on the relative location of HBP lead and TAVR valve. The damage caused by mechanical injury during valve replacement might be beyond His bundle or even distal, HBP may or may not correct LBBB. Therefore, in addition to the threshold problem, HBP also has the problem of uncertain success rate [55]. Sen et al. [63] reported a case of TAVR-induced new onset LBBB failed to be corrected by HBP, meanwhile De Pooter et al. [64] reported a correction rate of 69% (11 of 16) with HBP in patients with post-TAVR LBBB. However, higher pacing output negatively impacts on the therapeutic effectiveness and device longevity. Hence, LBBP could offer an alternative in post-TAVR patients with unsuccessful HBP. Vijayaraman et al. [68] reported the feasibility and success rates of HPCSP post-TAVR. In the study, 65 consecutive patients requiring pacemakers after TAVR was attempted at 5 centers, which included 18 LBBB patients. The success rate of LBBP was significantly higher than HBP (93% vs 63%), while the success rate of HBP distinctly varied among different valve types (69% in the Edward Sapien valve compared with 44% in patients with CoreValve; p 0.05). Zhang et al. [69] reported a LBBP case with heart failure by correcting TAVR induced LBBB with a stable capture and correction threshold, which failed to be corrected by HBP during the procedure. This is because LBBP is delivered by bypassing the pathologic region. In addition, Vijayaraman also confirmed the effectiveness and safety of HPCSP in TAVR-related conduction block, with significantly shortened QRS duration and stable pacing threshold during follow-up. Studies to evaluate HPCSP after TAVR are listed as follows (Table 2, Ref. [63, 64, 66, 67, 68, 69, 70]). Although the sample size of the above studies is small, the results are basically consistent. Therefore, different modalities can be selected according to the type, size, and implantation depth of TAVR valve. Fig. 2 summarizes the mechanism of physiological pacing after TAVR induced new onset LBBB by two kinds of commercially available prosthetic valves. Fig. 3 illustrates the electrocardiogram and imaging characteristics of HPCSP post-TAVR.

Table 2.Studies for evaluating HPCSP after TAVR.

Reference	Study Types	Pacing Modality	Year	Region	Sample Size	Main Point
Sen J et al. [63]	Case Report	HBP	2018	Australia	1	First report of new LBBB in the setting of TAVR corrected by pacing at the His bundle.
De Pooter et al. [64]	Prospective study	HBP	2018–2019	International	16	Permanent HBP is feasible in the majority of patients with TAVR requiring a permanent pacemaker with the potential to correct a TAVR‐induced LBBB with acceptable pacing thresholds.
Jincun G et al. [66]	Retrospective study	LBBP	2018–2019	China	20 (6)	LBBP was safe and feasible in patients with prosthetic valve (PV) implantation.
Patel S et al. [67]	Case Report	HBP	2020	USA	1	HBP might be a feasible option in a portion of complete heart block post-TAVR, and the valve, itself a fluoroscopic marker, can serve as an asset for His localization.
Vijayaraman P et al. [68]	Prospective study	HPCSP	2020	USA	65	HPCSP is feasible in the majority of patients requiring pacemakers post-TAVR. Success rates of HBP were lower in patients with Core Valves compared to Sapien valves. LBBAP was associated with higher success rates and lower pacing thresholds compared with HBP.
Zhang et al. [69]	Case Report	LBBP	2020	China	1	Rapid reversal of heart failure by correcting left bundle branch block induced by TAVR.
Cano Ó et al. [70]	EDITORIAL	HPCSP	2020	USA	N/A	The advent of LBBP provide another option for physiologic pacing in post‐TAVR patients with failed HBP attempts. His‐Purkinje conduction system pacing has the potential to become a standard pacing modality for these patients.

Fig. 2.

Summary of the concept: Mechanism of new onset LBBB after TAVR by two prosthetic aortic valves, and LBBB were corrected by two physiological pacing modes respectively. (A, B) The different location and depth of the mechanical damage caused by two different prostheses leading to different incidence of LBBB ((A) balloon expandable prostheses, (B) self-expandable prostheses). (C) Postoperative electrocardiogram showed LBBB and electrical dyssynchrony leads to mechanical dyssynchrony indicated by Phase standard deviation (PSD) on echocardiogram. (D, E) Due to the different length of the lesion, the correction rate of LBBB by HBP is also different (self-expandable valves are much higher), when the conduction disorders extend beyond His bundle or even further, HBP is unable to correct LBBB or requires a higher threshold. LBBP that bypasses the pathologic region, which is deeper and more distal, showed a higher success rate. (F) Electrocardiogram showed LBBB was corrected by LBBP, presented a typical pattern of RBBB and mechanical asynchrony improved with electrical synchronization, with a lower PSD.

Fig. 3.

Electrocardiogram and imaging characteristics of His-purkinje conduction system pacing post-TAVR. (A) The 12-lead ECG shows LBBB and His potential at baseline, as shown by the arrows, followed by bipolar pacing from the HBP (2V) and LBBP (1V), LBBB were both corrected. (B) Left anterior oblique (LAO) view of the HBP/LBBP lead and the relative location of the prosthesis.

Up to now, there is no guidelines particularly for pacemaker or CRTP/D implantation in TAVR induced new onset LBBB patients with cardiac insufficiency. Ventricular electrical activity dyssynchrony caused by LBBB can counteract the positive effect of TAVR on cardiac function, leading to poor recovery of LVEF. It’s difficult to estimate how much LBBB contributes to a patient’s ejection fraction decline. Further data of prospective studies are needed to evaluate the clinical outcome of pacing with biventricular or His-purkinje conduction system in patients requiring PPI after TAVR.

In the study of Urena [71], 8.1% of patients with new onset LBBB post TAVR had intermittent LBBB during preoperative ECG monitoring, and 31.4% of patients with PPI had high degree AVB, severe bradycardia or other indications of pacemaker implantation before TAVR. This suggests that there are many unrecognized baseline conduction abnormalities in TAVR patients and that the true incidence of conduction abnormalities derived from TAVR may be lower than published results so far. As we described above, it is recommended to monitor patients to receive TAVR using a long preoperative ECG to identify preexisted arrhythmias, to accurately predict the risk of intraoperative and postoperative conduction block, and perform drug or pacing interventions in advance if necessary. At present, routine continuous ECG monitoring and implantation of the temporary pacemakers during TAVR can help identification of intraoperative and early postoperative conduction block timely, and rapid pacing can be used when necessary to avoid serious conduction block related to procedure. Postoperative monitoring of 12-lead electrocardiogram also showed a certain predictive value. The sensitivity and specificity of newly diagnosed cardiac conduction disorders (first-degree AVB, LBBB, RBBB, etc.) were 99% and 39%, respectively. However, patients with no postoperative ECG conduction disorder and who are stable within 48 hours do not develop delayed high AVB within 8 days after TAVR [72]. After discharge, electrocardiogram changes should be regularly followed up, and the monitoring frequency can be appropriately increased for high-risk patients.

New onset LBBB remains the most common complication of TAVR procedure. The most relevant contributing factor has been identified as the depth of artificial valve implantation. New onset LBBB may have potential adverse effect on LVEF and poor prognosis, although current data regarding for LVEF and mortality have shown conflicting findings. To date, there is no indication for prophylactic PPI in new onset LBBB patients. However, a subgroup of patients with very long PR interval ($>$240 ms) or QRS duration ($>$150–160 ms) may benefit from PPI. To avoid the deterioration of cardiac function and economic burden caused by PPI, the application of HPCSP in TAVR related LBBB or in even other conduction system disorders has shown a promising prospect. The PARTNER 3 trial initiates the era of applying TAVR in patients of low surgical risk [72]. With the expansion of TAVR indications, more people may face TAVR-related conduction block in the future. The rising incidence of post-discharge conduction abnormalities including new onset LBBB requiring a pacemaker after TAVR suggests the need for careful monitoring. The pacing decision should be carefully made according to the different clinical characteristics of patients and the severity of conduction block. Among them, new onset LBBB after TAVR with high risk factors should be treated with PPI as early as possible. It is necessary to evaluate the appropriate pacing mode before pacing procedure. Physiological pacing provides an alternative once the pacing indication is explicit. The strongest indication for LBBP/HBP, other than conventional CRT, in patients with heart failure is still unclear. The physiological pacing research team is still searching for patients who may benefit from HPCSP. Actually, patients with normal QRS duration who develop LBBB immediately post TAVR, especially those combined with cardiac insufficiency, provide an excellent model to restudy the mechanism of LBBB and the indication for CRT implantation.

As the rapid development of TAVR procedures, the occurrence of conduction disturbances, particularly of new onset LBBB after TAVR remains an important issue. Patients who develop new onset LBBB should be closely monitored for progression of heart failure, and LBBB correction using physiological pacing serves as an effective alternative strategy. Further studies are warranted to elucidate the clinical impact of new onset LBBB, the pathophysiological basis of new onset LBBB, the factors that influence its outcome, the optimal timing and indication for pacing, and long-term clinical outcomes and safety of physiological pacing in this setting.

JFZ and YWP designed and performed the research study. JFZ and YWP reviewed literature and wrote the manuscript. BW and GSF provided help and advice on the manuscript. All authors read and approved the final manuscript.

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This research received no external funding.

The authors declare no conflict of interest.