Discussion
We systematically reviewed 10 original studies comparing LBBP and BVP CRT, which were comprised of patients from 15 centers around the world. This is the largest, most up-to-date systemic review and meta-analysis to demonstrate the effectiveness and safety of LBBP CRT to our knowledge. We found 1) performing LBBP compared to BVP is associated with shorter procedure and fluoroscopy time. 2) LBBP is associated with a greater reduction in QRSd and greater LVEF improvement. 3) A composite of HFH hospitalization and all-cause mortality had a greater reduction with LBBP as well as a greater improvement in overall function. However, the reported mortality was low and there was no difference in all-cause mortality alone. The overall implant success rate was approaching 90% and complication rates were low. Comparison of implant success rate of LBBP and BVP was not performed because most included studies only included historical cohor for BVP which only consist of successfully implanted cases.
Since the introduction of LBBP, multiple studies have explored the feasibility, safety, and clinical comparison of other existing pacing methods in various indications including heart failure requiring CRT23-30. A previous study had shown LBBP, if optimized AV delay, can achieve better interventricular synchrony compared to BVP in ex-vivo heart models18. A retrospective cohort of 34 patients who underwent LBBP CRT with a follow-up period of 12 months observed a significant decrease in QRSd, and improvement in LVEF, LVEDD, NYHA classification, brain natriuretic peptide (BNP) level, and 6-minute walk test (6MWT). The success rate of LBBP in the cohort was 100% with stable pacing capture threshold and R-wave amplitude at the end of 12 months follow-up23. Another study that compared CSP (87 HBP and 171 LBBP) and BVP also noted a significantly narrower QRSd, greater LVEF improvement, and lower composite of HFH and mortality31.
Our findings were also consistent with recently published Left bundle branch area pacing outcomes: the multicenter European (MELOS) study and the Left Ventricular Activation Time Shortening With Conduction System Pacing vs Biventricular Resynchronization Therapy (LEVEL-AT) trial32, 33. The MELOS study was a registry-based observational study comprised of 2,533 patients attempted LBBP with 27.5% of whom had an indication from heart failure. The reported implant success rate in heart failure indication was 82.2%, which was similar to our finding. The overall complication rate of LBBP in the MELOS study was 11.68% mainly driven by lead complications including left ventricle perforation and dislodgement, which was much higher than our finding. The LEVEL-AT trial was a randomized controlled noninferiority trial that compared ventricular synchrony in CSP including HBP and LBBP with BVP in HFrEF patients with indications for CRT. Of the 35 CSP patients included, the majority of them were allocated to LBBP (80%). It showed ventricular synchronization achieved by CSP was non-inferior to BVP. There was a trend towards a greater QRSd reduction and a lower composite of HFH or mortality after a 6-month follow-up period but no difference in LVEF improvement. The implant success rate of LBBP was 82% which was similar to our finding. The high crossover rate (8/35 crossed over from CSP to BVP and 2/35 corssed over from CVP to CSP) and small sample size of the trial might limit further interpretation of results.
The improvement in interventricular synchrony by EKG findings (QRSd) and clinical outcomes we had observed may not be limited to HFrEF patients but to patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with midrange ejection fraction (HFmrEF), as one recent study suggests27. Echocardiographic parameters of interventricular synchrony assessment including interventricular mechanical delay (defined as difference between the pre-ejection intervals from QRS onset to the beginning of ventricular ejection at pulmonary and aortic valve level), the regional time intervals of left ventricular 12 segments between the onset of the QRS complex and the peak of systolic myocardial velocity during the ejection phase (Ts), standard deviation of Ts (Ts-SD) and peak strain dispersion had greater improvement with LBBP compared to BVP but they were only studied in two of included studies34, 35.
Despite LBBP having greater hemodynamic improvement as well as lower HFH in our analysis, we did not observe a clear benefit in all-cause mortality compared to BVP CRT, which can be attributed to the short follow-up period by most studies included. This was evidenced by the lower-than-expected mortality rate. The short follow-up can also potentially preclude the delayed effect in mortality benefit by improved interventricular synchrony and hemodynamics.
In patients with failed BVP due to CS lead failure or nonresponsive to BVP, it has been demonstrated that LBBP can be a safe and viable alternative 36. In the 2021 ESC Guidelines on Cardiac Pacing and CRT, there was no official recommendation for LBBP pending more evidence for long-term safety and efficacy from randomized trials37.
With shorter procedural and fluoroscopy time and possible improved clinical outcomes, LBBP is a promising and emerging alternative to BVP. Further studies, especially randomized controlled trials are required to demonstrate the long-term safety and efficacy of LBBP, and further, elucidate the clinical benefit of LBBP CRT. ChiCTR200028726 is an ongoing single-center randomized controlled noninferiority trial aiming to recruit 180 patients with HFrEF and indication of CRT38. Patients will be randomized at a 1:1 ratio to LBBP or BVP CRT. The recruitment period concluded in December 2022. The completion of this trial and other ongoing trials can potentially better demonstrate the role of LBBP CRT.