A Growing Body of Evidence Supports Left Bundle Branch Pacing

By Joshua D. Moss, MD

Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco

SYNOPSIS: Several late-breaking trials presented at the annual Scientific Sessions of the Heart Rhythm Society add to the data for left bundle branch pacing as an alternative to biventricular pacing for cardiac resynchronization therapy.

In the rapidly evolving discipline known as conduction system pacing (CSP), His-bundle pacing (HBP) has become supplanted by left bundle branch area pacing (LBBAP), in which a lead is fixated even more deeply in the interventricular septum to target the LBB for capture. The physiologic benefits of LBBAP appear like those found with HBP, with the apparent advantages of more forgiving lead positioning requirements and more stable long-term pacing parameters. Several late-breaking clinical trials focused on LBBAP were presented at the 2022 Scientific Sessions of the Heart Rhythm Society.

Zou J, Fan X, Wang Y, et al. Left bundle branch pacing versus biventricular pacing in cardiac resynchronization therapy: A randomized, controlled pilot trial. In this prospective trial, 40 patients (50% male, mean age = 64 years) with non-ischemic cardiomyopathy, LBBB, and an indication for cardiac resynchronization therapy (CRT) were randomized to standard biventricular (BiV) pacing or LBBAP. The primary endpoint was change in ejection fraction (EF) from baseline to three and six months after implant. Crossover was allowed for failed implant, which occurred in 10% of the LBBAP group and 20% of the BiV pacing group.

Using an intention-to-treat analysis, EF improvement was significantly greater in the LBBAP group, with 21.1% mean improvement vs. 15.6% with BiV pacing by six months. There also were significantly more “super-responders” and significantly greater reduction in NT-proBNP levels in the LBBAP group, although changes in QRS duration and New York Heart Association (NYHA) class were similar between groups. (Learn more here.)

Vijayaraman P, Zalavadia D, Haseeb A et al. Clinical outcomes of conduction system pacing compared to biventricular pacing in patients requiring cardiac resynchronization therapy. Heart Rhythm 2022; Apr 29:S1547-5271(22)01947-6. doi: 10.1016/j.hrthm.2022.04.023. [Online ahead of print]. In this retrospective analysis of an observational registry at two major health systems, the authors compared outcomes of 258 patients who were treated with CSP (66% LBBAP and 34% HBP) to 219 patients who were treated with BiV pacing. All patients underwent pacing as a class I or class II indication for CRT and had EF less than or equal to 35%. Baseline NYHA class was slightly but significantly higher in the BiV pacing group, and baseline QRS duration was significantly longer (mean = 161 msec vs. 151 msec), with a higher proportion of LBBB. Pacing thresholds were higher with coronary sinus left ventricular leads compared with HBP or LBBAP lead, but remained stable through longer than two years of follow-up. QRS duration decreased more with CSP than BiV pacing, and EF also improved more (from mean 26.4% to 39.7% vs. 26.1% to 33.1%; P < 0.001). Conduction system pacing was associated with significantly lower risk for the combined primary endpoint of death or hospitalization for heart failure (28.3% vs. 38.4%; HR, 1.52; 95% CI, 1.08-2.09), driven primarily by reduction in hospitalization. An even greater effect on the primary outcome was noted in the subgroup of patients with baseline LBBB (20.8% vs. 35.5%; HR, 2.1; 95% CI, 1.24-3.53). (Learn more here.)

Vijayaraman P, Herweg B, Verma A, et al. Rescue left bundle branch area pacing in coronary venous lead failure or nonresponse to biventricular pacing: Results from International LBBAP Collaborative Study Group. Heart Rhythm 2022; Apr 30:S1547-5271(22)01948-8. doi: 10.1016/j.hrthm.2022.04.024. [Online ahead of print]. This was a retrospective, observational study of 212 patients at 16 international centers who underwent attempted “rescue” LBBAP after failed BiV pacing. LBBAP was deemed successful in 200 patients, with inability to penetrate the septum the most common reason for failure. Of those 200 patients (64% male, mean age = 68 years), 156 underwent LBBAP because of failure to achieve favorable coronary venous lead position or need for extraction of a coronary venous lead; 44 were “non-responders” to BiV pacing (< 5% improvement in EF and worsening or unchanged NYHA functional class). There were 10 complications, seven of which were intraprocedural septal perforation requiring repositioning without further consequence. Through 12 months of follow-up, there was significant improvement in QRS duration, NYHA functional class, LV end-diastolic diameter and volume, LV end-systolic volume, and LVEF with LBBAP. The patients implanted for failure to achieve favorable coronary venous lead position fared significantly better than those who had not responded to BiV pacing, with improvement by at least one NYHA functional class in 69% vs. 45%, echocardiographic response in 68% vs. 40%, echocardiographic “super-response” in 32% vs. 9%, and freedom from death or hospitalization for heart failure in 87% vs. 70%. (Learn more here.)

COMMENTARY

Permanent HBP, in which a pacemaker lead is fixed directly into or immediately adjacent to the penetrating bundle of His, saw a marked increase in research and clinical adoption in the late 2010s. Studies of HBP for CRT progressed rapidly, from demonstration of the technique as a “rescue” strategy for failed BiV pacing to a potentially viable alternative first-line strategy. However, His-bundle lead implantation could take longer than BiV implantation, and long-term stability of sensing and pacing parameters often was poor in clinical practice, with a high rate of lead revision required. Thus far, experience with LBBAP has suggested a more forgiving initial implant experience given a larger target area, as well as more stable lead parameters. These late-breaking clinical trials further suggest the CRT benefits in the short-term are equivalent to or even better than those achieved with BiV pacing. Many already consider LBBAP an excellent first-line approach for patients with normal EF who will experience a high burden of ventricular pacing. Many operators also were comfortable with using LBBAP as a “rescue” strategy in patients with a clear indication for CRT for whom coronary venous pacing is unachievable or unsuccessful. Despite the limitations as a retrospective, observational trial, the late-breaking rescue LBBAP trial certainly suggests good electrocardiographic, echocardiographic, and clinical outcomes for those patients, for whom the only practical alternative would be a surgically implanted epicardial LV lead. Non-responders to BiV pacing also saw positive results, although prospective, randomized data are needed to prove the risks of an additional implant procedure are fully justified.

The remaining question is whether LBBAP will be equivalent to or superior to BiV pacing as a first-line approach to CRT. Traditional CRT using BiV pacing with a coronary venous epicardial LV lead has a proven mortality benefit in well-selected patients, while primarily intermediate endpoints are available for LBBAP. However, I expect conduction system pacing will become a standard of care in CRT.

A more reliable and robust response in a larger group of patients currently appears likely, with little reason to believe the implant procedure itself will pose higher risk than that of biventricular devices. In fact, lower pacing thresholds may translate to less surgical procedures (i.e., generator replacements) over the patient’s lifetime. If LBBAP leads prove durable, as was true with HBP, cardiologists and their patients will benefit from understanding all the options for CRT available, and from working with an electrophysiologist facile with multiple tools and techniques.