LBB Area Pacing Outperforms Biventricular in CRT: Large, Observational Study

Patients with indications for cardiac resynchronization therapy (CRT) have better clinical outcomes when they undergo left bundle branch area pacing (LBBAP) rather than conventional biventricular pacing, according to an observational analysis of more than 1,700 patients treated across 15 centers around the world.

The results were presented at the recent Heart Rhythm 2023 meeting and published simultaneously online in the Journal of the American College of Cardiology.

CRT with biventricular pacing “is a well-established therapy in patients with left ventricular ejection fraction that’s less than 35%, heart failure, wide QRS, [and] need for frequent ventricular pacing,” Pugazhendhi Vijayaraman, MD (Geisinger Heart Institute, Wilkes-Barre, PA), said in a late-breaking trial session. But LBBAP, he added, “has recently gained quite a bit of momentum as a safe and effective alternative to biventricular pacing.”

Indeed, conduction-system pacing—either at the level of the His bundle or, as is the case here, the LBB—is beginning to emerge as an alternative. The latest recommendations from the European Society of Cardiology, a consensus statement from the European Heart Rhythm Association and, as of this week, the Heart Rhythm Society-led pacing guidelines all point to a role for conduction-system pacing in practice. Still, evidence for biventricular pacing far surpasses what’s known about the newer option.

What stands out about the current study is that it “provided real-world evidence of the efficacy of LBBAP,” Vijayaraman told TCTMD in an email. “More importantly, LBBAP was associated with better outcomes (combined endpoint of heart failure hospitalization and mortality outcomes),” he said, noting that LVEF improved to a greater extent as well.

As a whole, the findings make a strong case “that this physiologic approach is likely to yield better outcomes than traditional biventricular pacing,” added Vijayaraman.

International LBBAP Collaborative Study Group

For their study, researchers from the International LBBAP Collaborative Study Group analyzed data on 1,778 patients with LVEF ≤ 35% and class I or II indications for CRT who were treated at 15 centers (six in North America, seven in Europe, and two in Asia) between January 2018 and June 2022. Among them, 55.2% underwent biventricular pacing and 44.8% had LBBAP. Treatment choice was based on operator preference and/or the institution’s clinical practice. At six centers, biventricular pacing was the first choice for all operators, while at five centers, LBBAP was the first choice. In the remaining four centers, operators varied in their choice.

Patients’ mean age was 69 years, one-third were female, and half had CAD. Mean LVEF prior to the intervention was 27%, and mean QRS duration was 160 ms. For 36% of patients, the etiology of cardiomyopathy was ischemic, and for 58% it was nonischemic. The remaining 6% had mixed etiology. Six in 10 patients had left bundle branch block (LBBB).

Most characteristics were similar in the two groups, though the biventricular-pacing patients had a higher prevalence of ischemic cardiomyopathy and LBBB. In terms of procedural differences, patients in the LBBAP group were more apt to receive a permanent pacemaker and those in the biventricular-pacing group had a greater use of defibrillators. Procedure duration was longer with LBBAP (mean 142 vs 124 min; P < 0.001), though fluoroscopy duration did not differ.

With LBBAP, mean QRS duration was narrower compared with baseline (128 vs 161 ms) and when compared with biventricular pacing (144 ms; P < 0.001 for both). Mean LVEF significantly increased with both LBBAP (from 27% to 41%) and biventricular pacing (from 27% to 37%), but the change was greater following LBBAP (P < 0.001) and among patients who had LBBB.

Mean follow-up duration was 33 months. The primary outcome, a composite of death or heart failure hospitalization, was more common after biventricular pacing than after LBBAP (28% vs 21%; P < 0.001), a difference that remained significant on multivariable regression analysis (HR 1.495; 95% CI 1.213-1.842). In the LBBB subgroup, the difference in the primary endpoint was even larger (biventricular pacing vs LBBAP HR 1.543; 95% CI 1.150-2.071).

Overall, when compared to biventricular pacing, use of LBBAP was linked to a reduction in heart failure hospitalization but not in death.

Building the Evidence Base

Vijayaraman acknowledged that there could be some confounding due to the reasons why some operators chose one method over another in the study. “We need randomized clinical trials to show us the true benefit using conduction-system pacing in all patients,” he stressed.

Julia Indik, MD, PhD (University of Arizona, Tucson), the discussant following Vijayaraman’s presentation, pointed out that LBBAP was only introduced around 6 years ago. She, too, drew attention to the lack of large RCTs of conduction-system pacing. For His-bundle pacing, there’s His-SYNC and His-Alternative, with 41 and 50 participants, respectively. For LBBAP, there’s the 40-patient LBBP-RESYNC trial. Also at the meeting, Vijayaraman presented 6-month data from the small but randomized HOT-CRT. The pilot study of 100 patients with LVEF < 50% and a class I or II indication for CRT found a greater improvement in ejection fraction with conduction-system versus biventricular pacing at 6-month follow-up.

“On that background, we have mostly observational evidence to help motivate us for the use of left bundle branch area pacing,” said Indik, citing three studies to make her case. “The message that comes out from all of this is the QRS is narrowed, the ejection fraction improves, and the outcome of death or heart failure hospitalization also improves with [LBBAP].”

Thus, the “amazing results presented today” from the International LBBAP Collaborative Study Group, with the cohort size reaching nearly 1,800 patients, represent a step forward, she noted. “Now, we need to think about our other opportunities for study.”

Indik proposed taking a closer look at results for women, who are known to gain more from biventricular pacing than are men, and teasing out differences in etiology. Registries are informative, but large RCTs are crucial, she added.

As to why the large RCTs haven’t yet happened, “the major reason . . . apart from the relative novelty of this technique is the lack of funding to perform large randomized studies,” Vijayaraman noted to TCTMD.  “Traditionally, device therapies are supported by clinical trials sponsored by the industry. Lack of industry enthusiasm so far has hampered these efforts.”

However, this is soon set to change, said Vijayaraman. “Thankfully, several investigators have started randomized clinical trials in this space.” He highlighted the Left vs Left Randomized Clinical Trial, set to enroll 2,300-plus participants, as one to keep an eye on. The largest trial thus far, Left vs Left is receiving support from the Patient-Centered Outcomes Research Institute.