6.3. Role in CRT
The electrocardiographic feature of inter-ventricular dyssynchrony is the QRS widening, which manifests as either Right BBB (RBBB) or Left BBB (LBBB). On the other hand, there is the intra-ventricular dyssynchrony, which refers to the late activation of the lateral regions of the left ventricular chamber as compared to the interventricular septum, existing in patients with heart failure, regardless of QRS duration. Especially for patients with LBBB, the role of biventricular pacing is proven beneficial, both in narrowing the QRS duration and in clinical endpoints. In 1977, Narula in 27 patients showed that by pacing the His bundle, LBBB is corrected, suggesting a longitudinal dissociation in the His Bundle and proposing the concept of “sinoventricular conduction”.43 Narula’s theory is based on the hypothesis that stimulation at a constant cycle length, at a slightly distal site, can abolish the LBBB (constant or rate related) due to synchronous impulse conduction to both the bundle branches. These early conclusions confirmed by a recent mapping study from Upadhyay et al. (2019) with 85 patients. This study reported that LBBB patterns comprise a set of partial disorders that can range from complete conduction block when this is intrahisian to no discrete block and intact Purkinje activation, when the block is more peripheral, in the left anterior and posterior fascicles. In patients to whom HBP attempted, block correction achieved in 94% of patients with left intrahisian block and none with a peripheral disorder at the level of the fascicles confirming thus the theory of intracardiac delineation of the septal conduction system, proposed almost half a century ago.44
The achievement of block reversal with HBP is reached either by placing the His lead further from the lesion if it is relatively proximal to the His bundle or by remote electrical activation, considering higher outputs, with all that this implies for the battery longevity. Moreover, the same may be achieved by retrograde activation of the His-Purkinje system via capture of an upper septal branch when His lead is fortuitously placed in close proximity with one of these many left bundle septal branches.45 Especially when the pacing is selective, the corrected morphology of paced QRS can be maintained even with chronic pacing, as also happens with mean thresholds. Subsequently, this electrocardiographic notification of BBB correction with HBP in those patients led to studies that attempted to demonstrate and correlate this correction with clinical benefits.
Several studies, though with few patients, showed non-inferiority of HBP in CRT compared to biventricular pacing. Barba-Pichardo et al. (2013) in 9 patients, Lustgarten et al. (2015) in 12 patients, Ajijola et al. (2017) in 16 patients, and Shan et al. (2018) in 16 patients recorded an improvement in LVEF and LV dimensions and reduction in NYHA class compared with baseline. 46-49 In these studies, in addition to LVEF, an improvement was observed in other echocardiographic parameters, such as the disappearance of a significant septal-to-posterior wall delay in colour tissue Doppler, as well the reduction in isovolumic contraction time, and increase in peak systolic velocity in Pulsed-wave tissue -Doppler. Secondary endpoints were also studied, such as the quality of life (QoL), 6MWT, and mitral regurgitation jet area, with a trend of improvement.
HBP especially gained remarkable worth in CRT as a solution in the case of failed LV lead implantation. This indication first studied by Giraldi et al. (2011), wherein 20 patients with unfavorable cardiac veins anatomy, an alternative CRT was attempted with a surgical minithoracotomic approach.50 The utilization of HBP lead as a general CRT alternative was also highlighted by Upadhyay et al. (2019) in a secondary analysis of the His-SYNC Pilot Trial. The study initially underlined the role of HBP in the QRS duration improvement and LBBB correction but failed to determine the advantage in hospitalizations and mortality.51 However, in cases of failure to place the LV lead in the coronary sinus, due to absence, tortuosity, or diameter <3mm of lateral or posterolateral vein or angle <60◦ of the lateral vein, HBP could be a reliable alternative to conventional CRT.
Another promising application of HBP in CRT was studied by Vijayaraman et al. (2019), with good results regarding QRS duration narrowing in the His-Optimized CRT study (HOT-CRT). In this study, in 27 heart failure patients presenting LBBB with QRS duration >140 msec and LVEF ≤35%, the RV lead placed in the His Bundle area and the LV lead synchronized in a time equal to the H-V interval with the His Bundle lead.52 An impressive reduction of QRS duration was recorded (from 183±27 msec to 120±16 msec), improvement of LVEF from 24±7% to 38±10%, and a change in NYHA functional class from 3.3 to 2.04, in 14- month follow-up. Similar results of this method observed in 11 patients with permanent atrial fibrillation and LVEF <40% by Boczar et al. (2019).53
Finally, the application of HBP showed the same good results in patients with RBBB, where the conventional CRT has a weaker class of recommendation. Sharma et al. (2018), in 39 heart failure and RBBB patients with QRS duration ≥ 120 msec and LVEF ≤50%, demonstrated a significant narrowing of QRS from 158±24 msec to 127±17 msec, an increase in LVEF from 31±10% to 39± 13%, and improvement in NYHA class from 2.8 to 2 with HBP in 15-month follow-up.54 All the above results for the beneficial effects of HBP in CRT come from observational, single-center studies, with a limited number of patients and for a relatively short follow-up period. As in the studies of the previous indications, for proof of these beneficial effects in primary clinical outcomes, such as hospitalizations and mortality, the authors also emphasize the need to carry out large RCTs.