Conduction system pacing compared with biventricular pacing for cardiac resynchronization therapy: a systematic review and meta-analysis

Background Conduction system pacing (CSP) has emerged as a physiological alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and meta-analysis aimed to comprehensively compare the clinical efficacy and safety of these two strategies using the most up-to-date evidence. Methods PubMed, Embase, Web of Science, and Cochrane Library were systematically searched up to March 2026 for randomized controlled trials (RCTs) and observational studies comparing CSP with BVP in adult HF patients (LVEF ≤ 50%). Primary outcomes included changes in LVEF, NYHA class, QRS duration, HF hospitalization (HFH), and all-cause mortality (ACM). Secondary outcomes included echocardiographic response, procedural parameters, and complications. Random-effects models were used. Heterogeneity was assessed using the I 2 statistic. Publication bias was assessed using funnel plots, Egger's test, and trim-and-fill analysis. Certainty of evidence was appraised using the GRADE framework. Results 35 studies (10 RCTs, 25 observational; N = 7,019) were included. Compared with BVP, CSP was associated with greater improvement in LVEF (MD: 4.22%, 95%CI: 2.74%–5.70%; I 2 = 72%), NYHA class (MD: −0.34, 95%CI: −0.47 to −0.21; I 2 = 30%), and QRS narrowing (MD: −19.60 ms, 95%CI: −24.18 to −15.02 ms; I 2 = 83%). CSP significantly reduced HFH risk (RR: 0.65, 95%CI: 0.49–0.87; I 2 = 50%) and echocardiographic non-response (RR: 0.58, 95%CI: 0.41–0.82; I 2 = 70%), while increasing super-response (RR: 1.86, 95%CI: 1.43–2.43; I 2 = 34%). ACM was comparable between groups (RR: 0.87, 95%CI: 0.62–1.22). CSP was associated with shorter fluoroscopy time (MD: −5.04 min, 95%CI: −8.62 to −1.45 min), with similar complication rates. Benefits were most pronounced in patients with classical CRT indications (LVEF ≤ 35% with LBBB) and confirmed conduction system capture. Publication bias was detected for LVEF; trim-and-fill analysis confirmed directional benefit (adjusted MD: 2.14%). GRADE assessment demonstrated low to very low certainty of evidence. Conclusion CSP may be associated with superior echocardiographic and electrocardiographic outcomes compared with BVP, but the overall certainty of the evidence remains low to very low. These findings should be considered hypothesis-generating and highlight the urgent need for large-scale, adequately powered RCTs to validate the potential benefits of CSP before its widespread adoption in routine clinical practice. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251074973 , identifier CRD420251074973.