Two studies recently published in JAMA Cardiology present conflicting findings in comparing conduction system pacing (CSP), such as left bundle-branch pacing (LBBP), and biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB).

The first study, presenting long-term outcomes from the HeartSync-LBBP trial, found that among patients with LBBB and LVEF ≤35%, LBBP showed reduced risk of death or HF hospitalization compared to BiVP.

Xueying Chen, MD, et al., enrolled 200 patients from six centers in China between October 2020 and March 2022, who were then randomized to receive either LBBP or BiVP. Median follow-up was 36 months, and the primary outcome was time to death due to any cause or HF hospitalization.

The primary outcome was lower in the LBBP cohort vs. the BiVP cohort (8% vs. 28%; hazard ratio [HR], 0.26; 95% CI, 0.12-0.57; p<0.001). Although there was no significant difference in all-cause mortality (2% vs. 5%; HR, 0.40; 95% CI, 0.08-2.04; p=0.25), patients who received LBBP saw a significant reduction in risk of HF hospitalization (7% vs. 28%; HR, 0.23; 95% CI, 0.10-0.52; p<0.001).

Echocardiographic response, defined as absolute increase in LVEF ≥5%, was similar in both groups, but super response, defined as absolute increase in LVEF ≥15% or improvement of LVEF to ≥50%, was higher in the LBBP cohort.

"We demonstrated that LBBP is superior to BiVP for the composite endpoint of all-cause mortality and [HF hospitalization]," write Chen and colleagues. "This was driven primarily by a decreased risk of [HF hospitalization] in the LBBP group. These findings might be explained by a greater improvement in electrical synchrony, ventricular remodeling, and consequent higher rate of super response in the LBBP group compared with the BiVP group."

The second study shared results from the PhysioSync-HF trial, where André Zimerman, MD, PhD, et al., found CSP to be inferior to BiVP in patients with symptomatic HFrEF and LBBB.

Enrolling 173 patients from 14 hospitals in Brazil between November 2022 to December 2023, they randomized participants to either CSP or BiVP with 12 months of follow-up. The study's primary outcome was a hierarchical composite of death, HF hospitalizations, urgent HF visits and change in LVEF at 12 months.

CSP was inferior to BiVP when looking at the primary outcome (odds ratio, 2.36; 95% CI, 1.37-4.06; p=0.99 for noninferiority; p=0.002 for between-group difference). In addition, patients who received CSP demonstrated a higher time-to-event composite of death, HF hospitalizations or urgent HF visits (HR, 2.35; 95% CI, 0.99-5.61), and the mean increase in LVEF with CSP vs. BiVP was 35% and 39%, respectively (mean difference, 3.8%; 95% CI, 0.3%-7.3%).

"The odds of a worse [HF]-related outcome were approximately [two]-fold higher with CSP compared with BiVP, driven by a higher incidence of clinical events as well as lesser improvement in LVEF," note Zimerman, et al.

Jens Cosedis Nielsen, DMSc, PhD; Henrik Laurits Bjerre, MD, PhD; and Jean-Claude Deharo, MD, PhD, authored an accompanying editorial comment on the two trials. "In carefully selected patients with truly correctable LBBB, treated by highly experienced operators achieving reliable left bundle-branch capture, CSP may offer superior resynchronization and clinical outcomes compared to BiVP," they state. "However, in more heterogenous populations where CSP is delivered with variable technical success, BiVP may be better than CSP."