By Joshua Moss, MD

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

SYNOPSIS: In a randomized trial of patients with heart failure and left bundle branch block, cardiac resynchronization therapy via permanent His bundle pacing produced similar short-term outcomes to traditional biventricular pacing, albeit with higher pacing thresholds.

SOURCE: Vinther M, Risum N, Svendsen JH, et al. A randomized trial of His pacing versus biventricular pacing in symptomatic heart failure patients with left bundle branch block (His-alternative). J Am Coll Cardiol EP 2021.

Permanent His bundle pacing, in which a pacemaker lead is fixed directly into or immediately adjacent to the penetrating bundle of His, has seen a marked increase in clinical adoption and research over the past several years. By directly stimulating the distal bundle of His and proximal left bundle, ventricular depolarization can be achieved physiologically via the native conduction system, sometimes reproducing a “normal” narrow complex QRS. Studies have shown the resultant cardiac resynchronization can result in improvement in symptoms and ejection fraction (EF) in patients with heart failure and left bundle branch block (LBBB).

Vinther et al sought to compare His bundle pacing to the currently accepted standard for cardiac resynchronization therapy (CRT): biventricular (BiV) pacing using a right ventricular (RV) and left ventricular (LV) lead. At a single center in Denmark, the authors randomized 50 patients with cardiomyopathy (EF ≤ 35%), symptomatic heart failure (New York Heart Association [NYHA] class II-IV) despite optimal medical therapy, and LBBB using strict diagnostic criteria (mean QRS width = 166 msec) to CRT via either His bundle pacing or BiV pacing. The patients were blinded to the type of treatment received, as were staff performing and assessing follow-up echocardiograms and hall walk tests.

All 50 patients were implanted successfully with either a His bundle lead or with an LV lead for BiV pacing. Of the 25 patients randomized to His bundle pacing, seven instead received an LV lead, mostly because of high left bundle capture thresholds. One patient even underwent re-operation for placement of the LV lead the following day. All patients who ultimately received a His bundle lead maintained His bundle pacing (with correction of LBBB) at six months of follow-up. In contrast, only one patient randomized to BiV pacing received a His bundle lead instead of an LV lead because of dissection of the coronary sinus during implant. One patient required replacement of an LV lead that dislodged three weeks after implant. There was no post-implant crossover between treatment groups.

Procedural times were longer, on average, for His bundle lead placement but statistically similar to BiV implant (P = 0.06), as long as patients did not require crossover. For the seven patients in whom His bundle lead placement was unsuccessful and LV lead placement was required, mean procedural time was nearly double that of upfront BiV pacing (172 minutes vs. 98 minutes).

Baseline values for LVEF, LV end-systolic volume, six-minute walk distance, and NYHA class were not different between groups. All parameters improved significantly by six months to a similar degree in both groups, whether compared using an intention-to-treat analysis or a per-protocol analysis. Absolute ejection fraction was higher and end-systolic volume lower at six months in the patients who actually received His-bundle pacing (per-protocol analysis), but NYHA class did not improve more than in the patients who received BiV pacing. Pacing thresholds were significantly higher for His bundle pacing at implant and six months.

The authors concluded that after a six-month follow-up, His bundle pacing resulted in similar clinical outcomes as traditional BiV pacing in patients who were candidates for cardiac resynchronization therapy. However, pacing thresholds were higher with His bundle pacing.

COMMENTARY

Previous studies have shown His bundle pacing can be a successful “rescue” technique for providing CRT to patients in whom traditional BiV pacing was not feasible or successful. It also has performed well as a first-line CRT in a subset of patients for whom adequate QRS narrowing could be achieved. Vinther et al randomized “ideal” CRT patients, with strict criteria for LBBB and mostly non-ischemic cardiomyopathy, to His bundle pacing or BiV pacing. Although still small and conducted at a single center with a relatively homogeneous patient population, the study adds valuable knowledge and highlights areas that will require further study.

His-bundle lead implantation takes longer than BiV implantation, at least for these operators who began their study more experienced with the latter technique. The authors did not comment on whether procedure times or the high rate of intraprocedural crossover from His bundle pacing to BiV pacing improved over the course of the study. It will be useful to know how steep the learning curve will be for implanters planning to try His bundle pacing, and whether failure to achieve satisfactory His bundle pacing (with long resultant procedure times) becomes less common with practice.

Once implanted, if His bundle capture and QRS narrowing is achieved, all the known benefits of CRT can be expected for many patients, perhaps even more dramatically than with BiV pacing. However, since CRT via BiV pacing has shown proven mortality benefit in well-selected patients, no such results have been shown for His bundle pacing. I do expect similar or even greater mortality benefit with His bundle pacing may be proven, but larger studies with longer follow-up are required.

His bundle leads have higher pacing thresholds than LV leads, and thresholds increase further, even in just the first six months after implant. I have found this to be true in my own experience. The need to carefully test and reprogram the lead multiple times is not uncommon. Over the long term, the risk of unanticipated loss of His bundle capture, plus the risks associated with more frequent operative procedures, may not be trivial. They could even negate the benefits when compared to traditional BiV pacing. Of note, there has been a recent shift in the electrophysiology community from His bundle pacing to left bundle branch pacing, using a slightly more aggressive technique to implant the lead deeper in the interventricular septum. Some operators have found more reliable results at implant and more stable pacing thresholds over time. Again, further study will be needed.

Some form of conduction system pacing may become a standard of care in CRT. For now, cardiologists and their patients benefit from understanding the available options for CRT, and from working with an electrophysiologist who has multiple tools in their armamentarium.