Aortic stenosis (AS) is one of the common cardiac valvular diseases in elderly patients. It is characterized by progressive valve stenosis. Due to the aging of the population, the prevalence rate is expected to double in the next 20 years. The survival period of patients with severe AS is greatly shortened and the mortality rate is very high [1, 2, 3]. Therefore, it is necessary to replace the aortic valve in time. However, most elderly patients are weak, have poor tolerance to surgical aortic valve replacement, and have high surgical risk. Minimally invasive transcatheter aortic valve replacement (TAVR) has become a viable alternative in such patients [3, 4, 5]. TAVR can improve the clinical outcome of these patients, but the related clinical complications are relatively serious and complex. Conduction abnormalities are among the common complications of TAVR, which may tend to limit the promotion of this surgery to younger, lower-surgical-risk, populations [6]. Left bundle branch block (LBBB) is the most common type of heart block after TAVR, and its incidence in the first-generation valves is 4–65% [7, 8, 9, 10]. Of the different types of conduction abnormalities, high-grade atrioventricular block (HAVB) is among the more serious, with an incidence of 10–25% [11]. Most of those patients need to receive an implanted permanent pacemaker (PPM). In recent years, the precision of surgical instruments has been improved and data from surgeries have accumulated, but the incidence of conduction abnormalities has not decreased [12, 13, 14]. Conduction abnormalities may lead to further deterioration of cardiac function in patients with AS, increase the risk of heart failure (HF) and death, and adversely affect prognosis. Accordingly, predicting, preventing, and treating heart block has become the next frontier for improving TAVR outcomes. The present study analyzed the risk factors of new-onset heart block after TAVR in patients with severe AS and HF.

The main findings of our study are as follows: (a) the prevalence of new-onset heart block was 34.4%, and permanent pacemaker implantation (PPI) was performed in 9.7% of the cases; (b) patients who developed new-onset heart block were more likely to have malignancy and AF, as well as higher levels of TC and LDL-C before TAVR; (c) multivariate logistic regression showed that high preoperative LDL-C and $△$QRS duration were important independent risk factors for heart block after TAVR.

Different complications can occur after TAVR, of which many have been identified as independent predictors of mortality [16, 17]. New-onset LBBB is one of the most common complications post-TAVR. At times, transient new-onset LBBB persists at discharge or by 30 days afterward in approximately 55% of cases, leading to a PPI in 10–20% of cases, most often for HAVB [8, 18, 19]. Previous studies have reported that new LBBB was associated with increased risks of late ($\ge$1 year after TAVR) all-cause mortality and HF hospitalizations [18]. Chamandi et al. [20] found that LBBB had no impact on long-term mortality or HF hospitalization post-TAVR, but did increase the risk of PPI and non-improvement in LVEF over time. Another 5-year follow-up study showed that new LBBB was associated with increased risk of HF hospitalizations [21]. The presence of HAVB after TAVR usually indicates deterioration of cardiac function and increased risk of death. Therefore, in the present study we sought to define the rates of heart block and identify risk factors of its development in this cohort. Previous studies have identified the following risk factors: male sex, aortic valve calcification (AVC), diabetes mellitus, AF, and surgical operation factors (pre-existing conduction abnormalities, valve type, larger prosthesis size, valve oversizing, and increasing implantation depth) [22, 23, 24, 25, 26]. Our study was not able to conclude that preoperative conduction abnormalities, valve type, valve size, surgical approach, and pre-dilation, are risk factors for new postoperative conduction abnormalities; this may be due to the small sample size. However, our research continues. We are collecting more TAVR cases to verify the currently recognized risk factors and to discover new risk factors for postoperative cardiac block, with a view to improving the prognosis of patients. Due to the fact that this was a dual-center study, there are a few missing data on the depth of valve implantation. We conducted a statistical analysis of existing data, and the results showed that there was no statistical difference in valve implantation depth between the two groups. In the future, we will collect more TAVR cases and supplement this information to study the relationship between valve implantation depth and postoperative conduction block. In addition to the above factors, our research found that high levels of LDL-C and a greater postoperative-preoperative difference in QRS duration were independent risk factors of heart block. At least two possible mechanisms may explain the higher rates of heart block in patients who had higher baseline levels of LDL-C. (1) Elevated levels of LDL-C are the major culprit in the development of atherosclerosis [27]. The high blood viscosity and atherosclerotic coronary stenosis in patients with dyslipidemia may lead to myocardial ischemia and hypoxia, and then promote the occurrence of heart block. (2) Anatomically, the atrioventricular (AV) bundle penetrates the central fibrous body at the right fibrous trigone and continues at the membranous part of the interventricular septum located in the area under the right and the noncoronary aortic cusps, forming the left bundle branch [28]. Damage caused by direct mechanical interaction of the valve stent frame with the AV conduction system in the left ventricular outflow tract may lead to new-onset LBBB or complete AV block after TAVR. Previous studies have confirmed that an increased level of circulating oxidized low-density lipoprotein (ox-LDL) is associated with worse fibrocalcific remodeling of valvular tissue in AS [29, 30]. The plasma level of ox-LDL was significantly associated with LDL-C [30]. Therefore, we speculate that (a) The higher the level of LDL-C, the more serious the degree of AVC. During valve implantation, pre-dilation, post-dilation, and valve expansion, produce radial force on the conduction system near the aortic valve. Especially when the aortic valve is severely calcified, the expansion of the artificial valve will push the calcified mass of the autogenous aortic valve to the surrounding tissue, which will intensify the compression effect on the conduction system and cause the occurrence of heart block. In addition, the uneven deposition of lipids in the valve may cause asymmetric calcification, which may cause the expanded prosthesis to deviate from the centerline in the direction of the area under the right and noncoronary aortic cusps. The consequent mechanical stress on the AV conduction system might be increased locally due to the uneven distribution of radial forces, which may lead to an increase in the probability of heart block. (b) The deposit of lipid particles in the conduction system as a result of its proximity to the aortic valve complex can lead to conduction abnormalities. Currently, Lipoprotein(a) [Lp(a)] is a research hotspot. Early studies have confirmed that high plasma Lp(a) concentration is a risk factor for cardiovascular disease, that is, myocardial infarction (MI) and atherosclerotic stenosis [31, 32, 33]. It is also a risk factor for postoperative cardiovascular and cerebrovascular adverse events in patients with acute MI undergoing percutaneous coronary intervention [34]. Recent studies have shown that Lp(a) is an important risk factor for incident AS [35, 36]. And it is also a component of LDL-C [37]. The statistical results of most of our data showed the proportion of patients with elevated Lp(a) levels in the heart block group is relatively high, but there is no statistically significant difference in preoperative Lp(a) levels between the two groups. We consider that this may be related to a small sample size. In future studies, we will include more research subjects, collect Lp(a) data, and further investigate whether it is a contributing factor to LDL-C-induced heart block. The $△$QRS duration was also a risk factor, suggesting that overall intraventricular conduction delays, which may be caused by damage to the left bundle branch, lead to LBBB, which in turn increases the probability of developing HAVB [38].

Altogether, these results suggest that prevention strategies such as smoking cessation, better control of blood pressure, and LDL-C reduction, can delay the progression of AS and associated conduction abnormalities, possibly by reducing inflammation [39, 40]. The impact of TAVR on the conduction system is dynamic; both the timing and duration of conduction block are uncertain, which adds difficulty to the management of related conduction abnormalities. Pacing is the most effective intervention for the newly emerged conduction block. However, the ideal timing of pacing therapy remains uncertain. The determination of the pacing treatment is usually based on the clinical judgment. It should be noted that conduction abnormalities can show delayed presentations, which may be related to tissue edema and late expansion of the prosthesis. If HAVB occurs after TAVR, a PPM is implanted. For high-risk LBBB patients, ECG monitoring can be extended to at least 2–4 weeks. If necessary, further electrophysiological examination can be performed [9]. After TAVR, if dynamic ECG monitoring is not available, ECG monitoring should be conducted regularly, especially focusing on the change of QRS duration, so as to identify high-risk patients with HAVB.

In the present study, several patients had received 24-h ECG monitoring before TAVR. Some were found to have previously unknown paroxysmal arrhythmia or transient conduction disorder, most of whom were asymptomatic. Thus, many baseline arrhythmic events in TAVR patients go undetected or unrecognized. This may lead to bias whereby the rates of new-onset heart block are overestimated. Due to its potential clinical benefits and relatively low cost, the recommendation is for ECG monitoring for at least 24 h before TAVR. For patients with newly discovered arrhythmia, appropriate therapy should be carried out promptly in accordance with the recommendations of current guidelines. The application of 24-h ECG may provide an opportunity to determine the actual incidence of tachyarrhythmias and bradyarrhythmias attributable to the transcatheter prosthesis and the TAVR procedure, which is substantial for the preoperational evaluation of the newer transcatheter valve systems or new indications of TAVR.

This study has some limitations that should be recognized. First, our study should be interpreted with caution due to relatively small sample size. Moreover, due to the routine joint analysis, there are a few missing surgical data. Second, some patients with severe AS did not have ECG monitoring for at least 24 h before surgery, which led to overestimation of abnormal conduction after TAVR. Finally, most patients for TAVR undergo only 12-lead ECG monitoring after TAVR so we inevitably lose some key information on intermittent conduction abnormalities.

Patients who developed new-onset heart block were more likely to have prior histories of malignancy and AF, and have higher levels of TC and LDL-C before TAVR. High preoperative LDL-C levels and higher $△$QRS duration were independent risk factors.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

TD, TL and FXR designed the research study. MD, LZW and TLL performed the research. LZW, NZ, LHW and TLL conducted data collection. NZ and GT provided help and advice on technology. TD and LHW provided help and advice on language. ZCX, GT and TNC analyzed the data. MD and LZW wrote the manuscript. FXR and TL conducted writing review. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was conducted in accordance with the Declaration of Helsinki. This study received ethics approval from Affiliated Yantai Yuhuangding Hospital of Qingdao University Ethics Committee. The ethics approval number is 2022-181. All individuals have signed informed consent.

We thank the patients and study coordinators who participated in this research. We would like to thank all our teachers who have helped us to develop the fundamental and essential academic competence.

This research received no external funding.

The authors declare no conflict of interest.