In the present meta-analysis, we found that, compared with BVP, HPSP produced narrowed QRSd, improved LV function and NYHA functional classification, higher echocardiographic and clinical responses significantly. In terms of hospitalization rate of HF, there was no difference between HPSP and BVP. As for threshold change, LBBaP was less than BVP, while there was no difference between HBP and BVP. To the best of our knowledge, this study is the first meta-analysis comparing the clinical efficacy between HPSP and BVP comprehensively. We used the net value between baseline and follow-up which reduced the risk of confounding bias, instead of adopting the final follow-up value to evaluating our results.
A wide QRS complex reflecting left-sided intraventricular conduction delay in patients with HF is associated with more advanced myocardial disease, worse LV function, poorer prognosis, and a higher all-cause mortality rate compared with patients with a narrow QRS complex (38). There are several determinants of successful response to CRT, QRSd and QRS morphology are of considerable importance in this response (39). Consistent with previous studies, our meta-analysis suggested that patients who received HPSP exerted a better synchrony of LV contraction and thus an improvement of LV function compared with BVP.
A better electromechanical synchronization can improve ventricular systolic function and symptoms of patients. LVEF is the central measure of left ventricular systolic function. CRT has been noted to improve LV function and NYHA functional classification (40), which was consistent with our analyses. CRT can reduce hospitalization rate of HF patients (2). Nine of twelve studies reported exact number of HF-hospitalization in this analysis. BVP had more rehospitalization patients than HPSP, but there was no difference between these two groups. Theoretically, the effect of disease history and medication status on hospitalization rate of HF patients who received CRT should be considered to minimize the confounding bias. Further high-quality RCTs should be developed to solve this problem.
The threshold of pacemaker affects its lifespan. Different area of cardiac produce diverse threshold. His-bundle is a thin cylindrical fascicle whose cell type is predominantly Purkinje type connecting the Atrioventricular (AV) node with the bundle branches. The penetrating bundle of His only continues for a small distance (1–3 mm). The narrow target zone and variable position make HBP lead implantation technically challenging and requiring greater precision and longer learning period. Otherwise, the dense fibrous tissue surrounding the penetrating His-bundle typically yields high capture threshold at implantation, and unpredictable delayed rise in threshold that can lead to premature battery depletion and lead revision (41). Nevertheless, in patients with AV node ablation, AV block and high right ventricular (RV) pacing burden, HBP is still considered an ideal and first-line strategy to achieve CRT as a physiological pacing producing electrical synchrony (13, 42). Relatively, BVP did not eliminate electrical dyssynchrony (43), although it had a similar threshold at baseline and change value to HBP in our analysis. With the clinical exploration and application of distal HBP pacing, it may be a good method to solve the problem of higher threshold.
LBBaP is a thick band like structure which contains abundant left bundle branch (LBB) and Purkinje fibers. A broad target area and dense muscular tissue wrapping them conduct electrical signal rapidly across the LV. Therefore, LBBaP has some unique advantages such as easier for leaning and lead implantation technically, higher success rate of implantation and lower threshold at baseline and change value than HBP and BVP (41). In our research, LBBaP had a slower upward trend than HBP and BVP in threshold, the battery of LBBaP could last longer theoretically. Besides, easier implantation procedure can avoid more X-ray and be safer. We did not analyze fluoroscopy time and operation cost because multi-center studies were included and the skill of implantation varied widely. The large single-center RCTs will be needed to evaluate them.
In conclusion, HPSP is associated with a shorter QRSd and thus a lower electromechanical dyssynchrony compared with BVP, and there may fewer adverse cardiac events. Nevertheless, there are still some patients who are not suitable for class I recommendations in the guideline or do not response to current CRTs. In order to benefit from CRT, patients need to be screened and stratification more carefully. Additionally, more optimized therapies should be further explored to treat the above patients.
Strengths and limitations
This study gave us a comprehensive understanding of physiological cardiac resynchronization therapy through comparing HPSP (HBP and LBBaP) with BVP by including studies with good quality, from different countries with different clinical characteristics of the population. Sensitivity analyses were conducted by systematically removing one study at a time, and no single study affected all the above results. The limitation of this study was the heterogeneity in the subgroup of QRSd (HBP vs BVP) and NYHA, which may be explained by small sample size, various follow-up duration and inconsistent baseline levels of QRSd and NYHA.
Clinical perspectives
In conclusion, the HPSP can produce shorter QRSd, higher LVEF and improved NYHA functional classification compared with BVP. Otherwise, LBBaP had a more stable threshold than BVP. These findings suggested that HPSP may be a promising frontline strategy for CRT. Further high quality RCTs should be performed to evaluate the efficacy between HPSP and BVP.