Aortic stenosis (AS) is the third most frequent cardiovascular disorder in ages over 60 years, following atherosclerotic disease and hypertension [1]. Although rheumatic valvulopathy is uncommon in developed countries, the global burden of AS is increasing due to aging and population growth. Indeed, various epidemiological data describe an exponential increase in AS prevalence with advancing age, ranging from 0.2% in the 50–59 year group, 1.3% in the 60–69 year group, 3.9% in of the 70–79 year group and up to 9.8% in those aged 80–89 years [2].

Transcatheter aortic valve implantation (TAVI) is the gold standard treatment approach to symptomatic severe AS in patients deemed to be at high surgical risk and indications have expanded to intermediate and low-risk patients [3]. However, despite recent advancements in TAVI implantation techniques and device technology, the occurrence of new impulse conduction abnormalities (CA), including high-degree atrioventricular block (HAVB) requiring permanent pacemaker (PPM) implantation, represents one of the main procedural complications ^[4][5][4,5]. This is particularly relevant as TAVI is now being offered to younger patients.

The AV node is located within the Koch’s triangle, which lies in the superficial paraseptal endocardium of the right atrium, and the emanating fibers subsequently form the bundle of His within the infra-anterior portion of the membranous septum (MS), which is in turn divided in the right and left bundle branches. The left bundle runs proximal to the base of the commissure between the non and right coronary cusp. Interindividual variations in the location of the bundle branches with respect to the membranous and muscular septum may explain the different risks of CA among patients ^[6][13].

Additionally, in patients with shorter MS length and thus a short distance between the His bundle and the aortic annulus, the risk of HAVB and PPM implantation was higher compared to those with longer length ^[7][14]. According to the MIDAS (Minimizing Depth According to the MS) technique, patients are classified into low (length > 5 mm), medium (length 2– 5 mm), or high risk (length <2 mm). Observational data have shown that patients with bicuspid aortic valves (BAV) have significantly shorter MS length and thus a higher risk of developing new LBBB, or requiring PPM post TAVI ^[8][15]. Therefore, MS is considered to be a surrogate marker for the location of the AV bundle; however, given the aforementioned anatomic variability, it may not be a reliable approach in a significant proportion of patients.

Another important predictor of PPM implantation after TAVI is an asymmetrically calcified aortic valve. The presence of a high calcium load on the left and non-coronary cusps is a potent factor for PPM implantation post TAVI ^[9][16]. This is likely attributable to an unequal distribution of radial forces on the aortic annulus and its adjacent structures, shifting the bio-prosthesis away from calcification, towards the RCC (where the bundle of His is located) ^[10][17]. The calcium distribution pattern is, thus, another important feature to be considered pre-TAVI.

ECG is a readily available and effective tool to assess and predict post-procedural CA and the risk of PPM implantation, with baseline CA being the most powerful predictor. A large meta-analysis including 239 studies with a total of 981,168 patients confirmed that the most relevant predictors for PPM implantation were pre-existing RBBB (RR, 3.12; p < 0.001), bi-fascicular block (RR, 2.40; p = 0.002) and isolated 1st-AVB (RR 1.44; p < 0.001) ^[11][18]. A recent retrospective observational single-center study with 720 consecutive patients who underwent TAVI showed that R-wave amplitude in lead V1 during baseline ECG in patients with normal QRS duration may predict the occurrence of HAVB following new LBBB post TAVI ^[12][19]. Interestingly, post-procedural bradyarrhythmic events are not necessarily TAVI-related and may be pre-existent. Twenty-four-hour ECG monitoring on the preprocedural day can detect new arrhythmias in 16.1% of patients and, among those who ultimately required post-procedural PPM, 31.4% had newly diagnosed HAVB or severe bradycardia pre-TAVI ^[13][20]. PPM implantation at late post-TAVI is uncommon and is associated with clinical symptoms in 50% of the cases ^[14][21].

Various scoring models for the prediction of PPM implantation post TAVI based on ECG criteria have been verified. In 2019, the Emory Risk Score was developed for the prediction of PPM implantation post TAVI ^[15][22]. Variables included were a history of syncope, RBBB, QRS interval ≥ 140 ms, valve oversizing ≥16% with an area under the receiver-operating characteristic (ROC) curve of 0.778 (p < 0.001) and an odds ratio of 2.2 per point increase (p < 0.001). More recently, another scoring system was introduced: transfemoral approach, LBBB without bradycardia, sinus bradycardia without LBBB, RBBB, LBBB with sinus bradycardia and 2nd -AVB taken into calculation with the area under the curve of 0.6743 (95% CI: 0.618 to 0.729). The risk for PPM was stratified as follows: 7% risk of PPM with a score ≤ 3, 19% with a score 4 to 6 and 38% with a score ≥ 7 ^[16][23].

Although divergent data have been reported, data from meta-analyses support the concept of a sex-associated risk of PPM implantation post TAVI, with males at higher risk. Although women have a higher risk of in-hospital mortality and vascular complications, men are more likely to require PPM implantation ^[6][17][13,24]. However, recent data from a retrospective study by the Netherlands Heart Registration contradicted the above, suggesting a protective role for male sex against PPM implantation, possibly due to larger aortic annuli and thus the reduced occurrence of oversizing ^[18][25].

The role of age as a predictor was studied in large national registries, such as in recent reports from France and Switzerland, which reported that older age was associated with higher PPM implantation risk ^[7][19][14,26]. Likewise, a sub-analysis of the PRAGMATIC registry found age to be predictive of PPM implantation (OR 1.08, 95% CI: 1.04–1.12, p < 0.0001) ^[20][27].

There are significant differences between the transcatheter device and the risk of PPM. A recent network meta-analysis analyzing 46,000 patients with post-TAVI PPM implantation revealed that (a) the implantation of balloon-expandable valves was associated with 39% and 62% lower PPM implantation rates compared to self-expanding and mechanically expanding ones, respectively; (b) the implantation of SEVs was associated with a 38% lower PPM implantation rate compared to MEVs; and (c) the ACURATE neo™ valve (Boston Scientific, MA, USA) was associated with the lowest post-TAVI PPM implantation rates ^[21][28]. A large meta-analysis demonstrated only 7.7% new PPM for the ACURATE neo due to its low radial force and predictable supra-annular deployment ^[22][29]. In the Evolut low-risk trial, 17.4% of patients received PPM, and the percentage was 6.6% in the PARTNER 3 trial [3]. Other large comparative meta-analyses confirm these notable differences among valve types.

Other predisposing factors for PPM implantation post TAVI are valve oversizing and high prosthesis/LVOT diameter ratio, leading to overstretching of the latter [5]. Pre-dilatation has historically been considered a mandatory step during TAVI to facilitate device crossing, deployment and optimal expansion. However, pre-dilation increases the annular trauma, and its role is still debatable. Randomized trials with the Evolut and Sapien 3 valves demonstrated non-inferiority of the direct TAVI with the pitfall of possibly more post-dilatations for the former device ^[23][30]. Balloon post-dilatation, though, may be potentially associated with PPM implantation and should be carefully considered ^[23][30].

Valve implantation depth is a well-known procedural risk factor for new-onset CA. Jilaihawi et al. proposed an individualized, anatomically guided tool for minimizing implantation depth according to a CT-measured MS (MIDAS strategy) as an important strategy to reduce CDs during TAVI ^[17][24]. The researchers found that high valve implantation at a depth shallower than the MS significantly reduced PPM implantation rates (from 9.7% to 3%) and new onset LBBB (from 25.8% to 9%). Less CA with low-depth deployment was also confirmed recently by Ochiai et al. with the drawback of higher coronary ostia obstruction rates ^[24][31]. The cusp-overlap projection is another technique facilitating a controlled implantation depth in case of SEVs. Cusp-overlap projection has the advantage of LVOT “elongation”, gaining a higher implantation depth (<3 mm), thus increasing the device positioning accuracy ^[17][24]. A recent propensity score analysis revealed an almost 50% reduction in PPM implantation rates with the cusp overlap technique versus the standard 3-cusp coplanar projection (p = 0.03) ^[25][32]. Data of the Optimize PRO study revealed improved safety and lower PPM implantation rates (9.8%, at 30 days) when the cusp overlap technique was used ^[26][33]. In addition, the deployment of balloon-expandable devices using the cusp overlap technique led to a more than 50% reduction in new LBBB occurrence and PPM implantation rates compared to standard projection (p < 0.001). On the other hand, balloon-expandable valves, characterized by short frame height, are usually deployed perpendicularly to the aortic annulus when the standard 3-cusp coplanar projection is used, thus minimizing the interference of the device with the anatomy of the conduction system.

Various medications may increase the risk of CDs and/or the need for PPM implantation following TAVI. These include antiarrhythmics, antihypertensives, psychoactives/neuroleptics and anticancer drugs (5-fluorouracil, cyclophosphamide, anthracycline, etc.) ^[27][34]. Several publications address the topic of beta blocker (BB) discontinuation in patients undergoing TAVI, yet it has not been adequately clarified whether the periprocedural continuation of BBs increases NOCDs and PPM implantation following TAVI, although there is indeed a tendency to withdraw them or to reduce the dose for PPM implantation prevention. In fact, the OCEAN registry showed similar rates of PPM implantation and better cardiovascular outcomes for the BB arm ^[28][35]. Moreover, prospective data revealed that the rate of periprocedural HAVBs and thus PPM implantation was lower among patients who continued BB versus those who did not (20% vs. 13%; p = 0.02). Interestingly, a multivariate analysis of the above-mentioned study revealed that the risk of periprocedural arrhythmic events is double in those who discontinue BB ^[29][36]. The BETA TAVI (NCT05721170), a prospective, multicenter RCT, will provide more solid data regarding the role of BBs in TAVI population.