This is the first study using CMR to investigate the impact of TAVR-induced LBBB on cardiac reverse remodeling in a matched population. The main findings of this study are 1) Those with a narrow QRS post-TAVR have better LVEF and GLS compared to those with LBBB-T 6 m post-procedure, 2) Patients with LBBB-T exhibited significant inter- and intra-ventricular dyssynchrony compared with those with narrow QRS and 3) Post-procedure QRS duration remained a significant independent predictor of change in LVEF and GLS following TAVR on multivariable analysis.
Impact of TAVR-induced LBBB on cardiac reverse remodeling
TAVR-induced LBBB is common, occurring in 16–65% patients depending on valve type . Although predictors of LBBB-T have been extensively studied , the impact of LBBB-T on cardiac reverse remodeling is less well described, with studies limited to echocardiographic evaluation and containing a heterogeneous mix of patients. A PARTNER echocardiographic sub-study reported a lower LVEF at 12 months in patients with LBBB on discharge electrocardiogram compared to those with a narrow QRS, however, there was an increased number of those undergoing trans-apical TAVR in the LBBB-T group , findings which were replicated in another similar study, again with more undergoing trans-apical TAVR in the LBBB-T group . Tzikas et al.  reported an 8% difference in LVEF between those with LBBB-T and nQRS prior to and 6 days following self-expanding TAVR. Longitudinal strain was also non-significantly reduced in those with new conduction abnormalities. Hoffman et al.  investigated 90 patients using 2D and speckle tracking trans-thoracic echocardiography prior to and at 1 and 12 months following TAVR. Patients with new conduction defects had a significantly larger LVESVi at 12 months compared with those with a narrow QRS, with less difference in LVEDVi, mirroring the findings in our study. New conduction defects and baseline LVEF were independent predictors of reduction in LVEF at 12 months. The inclusion of patients with trans-apical access in the majority of these studies [6, 11, 20] and those with post-procedural pacemaker insertion [6, 10, 11, 20] is a significant confounder, however, given that trans-apical access has been linked to reduced LVEF in a number of studies [20, 21] and pacing induced LBBB has been shown to cause different patterns of strain to those with idiopathic LBBB .
Our study adds further insight into the impact of LBBB-T on cardiac reverse remodeling. The accuracy and reproducibility of CMR means that important differences can be determined using studies 87% smaller than echocardiographically based studies, with only 11 patients per group required to detect a 3% difference in LVEF . Our study groups were matched for clinical and baseline CMR characteristics, all parameters which have been found to strongly influence reverse remodeling following valve intervention . None of the patients in our study received trans-apical TAVR or permanent pacemaker insertion and the unique ability of CMR LGE imaging allowed us to identify and exclude any patients who had a post-procedural myocardial infarction, another factor that may have confounded the earlier echocardiographically based studies. Finally, the two groups experienced similar amounts of post-procedural aortic regurgitation, which is an important modulator of post-TAVR reverse remodeling [23, 24], and which was not reported in most of the echocardiographic studies [6, 10, 11].
Inter and intra-ventricular dyssynchrony
The novel use of CMR feature tracking allows us to report values for intra- and inter-ventricular dyssynchrony. In LBBB, the normally functioning right bundle conducts the electrical impulse to the right ventricle prompting early right ventricular contraction followed by activation of the interventricular septum and finally lateral wall contraction resulting in inter- and intra-ventricular dyssynchrony. This dyssynchrony leads to the classical abnormal septal motion pattern of contraction seen in LBBB which is felt to impair LV filling and ejection in its own right (Fig. 3). This dysynchronous contraction leads to an increase in LVESVi, as seen in our LBBB-T group and it is this, rather than a change in LVEDVi that is the largest driver of reduction in LVEF. We have also shown that LBBB-T impacted on change in GLS, with no improvement in this group compared to a significant improvement in the nQRS group. Although GLS may be affected by dyssynchrony , this, coupled with the reduction in left atrial volume in the nQRS but not the LBBB-T group, and the reduction in LV stroke volume in those with LBBB-T, suggests that the effects of LBBB-T may go beyond that of simple mechanical dyssynchrony.
Conduction system damage during TAVR
It is well established that TAVR leads to conduction abnormalities . Trauma can occur at multiple time-points during the TAVR procedure; from guidewire manipulation, to during balloon valvuloplasty, device manipulation and valve deployment. It is likely that the different valve designs can cause differing degrees of compression to the conduction system; with the self-expanding Medtronic CoreValve felt to cause more compression of the LV outflow tract than the balloon expandable Edwards Sapien device . The unique design of the mechanically expandable and repositionable Boston Lotus valve with its adaptive seal, may also be associated with more conduction system trauma, although reports to date are limited . Global ischaemia during rapid pacing required for valve deployment may exacerbate the issue . Other procedure-related factors felt to be implicated include pre-implant valvuloplasty, deep implant, low ratio of the annulus:balloon or annulus:prosthesis and operator experience .
The impact of TAVR-induced LBBB on mortality is a subject of debate, however, it has been shown in many studies to be a predictor of mortality [3–5, 29] and has been associated with increased hospitalisation . Other studies have failed to demonstrate a link [12, 20, 30]. Nonetheless, LVEF is a strong independent predictor of long term survival . Our study has shown that TAVR-induced LBBB is associated with reduced global longitudinal and radial systolic function compared with those with a narrow post-procedure QRS, which could partially explain the link with mortality. Given the adverse effect of TAVR-induced LBBB on cardiac reverse remodeling, restoring inter- and intra-ventricular dyssynchrony using cardiac resynchronisation therapy, could be considered, especially if another conventional indication for device therapy exists. Furthermore, every effort should be made by the operator to reduce the risk of TAVR-induced LBBB given the adverse effects on ventricular remodeling seen. As newer devices are being developed, designs should be focused on minimising damage to the electrical conducting system in order to prevent the deleterious effects on the LV that this entails.
Although patients were recruited in a prospective manner, they were matched retrospectively and hence the study is prone to the selection bias of this type of study. Patients with LBBB-T were matched according to those factors known to influence cardiac reverse remodeling  but other factors may be unaccounted for. Specifically, patients with coronary artery disease and previous myocardial infarction were included in the study, however, numbers in each group were similar and infarct pattern LGE at baseline was not a univariate predictor of change in LVEF or GLS. Group allocation was based on the discharge electrocardiogram and not re-confirmed at 6 months, however, there are evidence to suggest that virtually all those with LBBB at discharge have persistent LBBB at 30 days following self-expanding TAVR . Furthermore, the demonstration of ongoing dyssynchrony at 6 m in the LBBB-T group suggests that the conduction abnormality was persistent. Finally, although adequately powered to detect a difference in reverse remodeling using the accurate technique of CMR, the study is small with a relatively short follow-up period and a larger study with a longer follow-up interval may be helpful to further investigate the impact of TAVR-induced LBBB on cardiac reverse remodeling.