This study demonstrates that physiologic pacing interventions, both HBP and LBBP, maintain normal physiology of cardiac conduction systems, as shown in the electrocardiogram (ECG) of patients requiring a permanent pacemaker. Further, these results support the hypothesis that pacemakers that use physiologic pacing cause less cardiac desynchrony compared to traditional RV pacing, consistent with a previous study that showed the HBP technique could improve cardiac function by maintaining myocardial segment electrical activation (4). In patients with preexisting bundle branch block, the long helix His bundle lead may penetrate distally to the level of cardiac conducting system blockage and normalize the QRS complex. While many theories have tried to explain this QRS normalization, functional longitudinal dissociation between bundle branches is believed to be the fundamental physiology of the change (33).
QRS duration is a powerful marker for cardiac dyssynchrony. The prolongation of QRS complex to ≥ 120 ms is associated with more advanced myocardial disease, poorer prognosis, and higher all-cause mortality compared to a normal QRS complex duration (34). In patients with an LVEF < 30%, QRS prolongation is associated with increased mortality and sudden cardiac death. Further, in patients with an LVEF of 30-40%, QRS prolongation is associated with increased mortality (35). QRS duration is the major determinant for cardiac resynchronization therapy according to current guidelines (36). The results from our study showed a significantly narrower QRS duration in patients with HBP and LBBP compared to BiV; thus, physiologic pacing can be translated into better cardiac performance by restoring normal interventricular electrical activation pattern.
The current guidelines recommend RV pacing- or BiV pacing-based interventions in patients with chronic atrial fibrillation and heart failure who underwent AV node ablation due to inadequate control of heart rate by medications (37). However, several studies have shown no benefit in patients with previously narrow QRS complex, which could be explained by remaining electrical dyssynchrony after BiV pacing (38, 39).
The implantation of His bundle pacing comprises delivery of the RV lead into the area of His Purkinje system with a 3830 pacing lead and C315 His non-deflectable sheath (40). Once the area of His signal is obtained, the lead is then screwed into myocardium (40, 41). The success rate of this procedure has been reported as up to 92% in experienced centers (42), and was found not to be different from the success rate of BV pacing (43). The issues with His bundle pacing that concern most operators are long-term lead stability and ventricular capture threshold. Primarily, the pacing output threshold, the least electrical energy delivered that triggers electrical depolarization, would increase overtime; 6.7% of patients required lead revision over 5 years of follow-up (42, 44). Another unresolved issue with HBP interventions is increased battery drainages secondary to higher ventricular capture thresholds (41). The implantation of left bundle branch pacing is similar to the HBP implantation procedure, with the same type of lead and sheath, as well as methods of delivering the lead, used in both implantation processes. The difference between LBBP and HBP procedures is that once the His bundle electrogram is obtained, the tip of pacing lead is moved 1.5-2 cm toward the ventricular apex on the right anterior oblique fluoroscopic projection, and pace-mapping is performed to secure lead in the ideal position (45). The successful LBBP would result in right bundle branch morphology with a QRS duration of less than 130 milliseconds. The issues with HPB (increased pacing and sensing threshold) do not occur in LBBP (23, 46).
Current evidence has pointed toward higher success rates and lower pacing thresholds in LBBP compared to HBP (47, 48). Although both techniques appear to be relatively safe in short-term follow-up and, theoretically, advantageous over conventional pacing, many questions remain to be answered in the clinical setting. For example, the mortality benefit and rate of heart failure hospitalization remain unknown for both procedures. Nevertheless, the results of the present study provided additional evidence to support that physiologic pacing, both HBP and LBBP, is associated with narrower QRS duration compared to conventional pacing. Narrowing of QRS duration is related to a lower electromechanical desynchrony, and thus, HBP and LBBP may confer lower incidence of adverse cardiac events from pacing-induced cardiomyopathy.
Limitations
QRS duration was the only parameter analyzed in our study. Other markers of synchronous contraction were not specified in included studies, precluding further analysis. Nevertheless, many studies have suggested QRS duration is the best surrogate marker for cardiac synchronicity (34, 49). Since physiologic pacing, particularly LBBP, has been in the early phase of trials, the lack of clinical endpoints is inevitable. Further studies are required to establish health impacts among patients receiving either HBP or LBBP. Secondly, half of the studies we included in our analysis were observational studies. Thus, residual biases cannot be completely excluded. Despite this caveat, NOS criteria were adopted to stratify biases risks as well as study qualities, suggesting robust analysis. Thirdly, the total number of patients in our study was small, possibly leading to an underestimation of the actual effects. Lastly, almost all the studies were done in centers with expertise in physiologic pacing. Therefore, the success rates and results might not be applicable to general or low volume clinical settings. Despite these limitations, this study is the first network meta-analysis to provide the most updated comparison of the performance of physiologic pacing compared to conventional pacing.