Keeping Pace: His-Bundle CRT for Heart Failure Impresses in Second Randomized Trial

April 27, 2021

The limitations of biventricular (BiV) pacing, successful as it has been at improving cardiac function and outcomes in many patients with heart failure, leave opportunities for more physiologic pacing alternatives to drive cardiac resynchronization therapy (CRT).

Both His bundle pacing (HBP) and left bundle pacing (LBP) have emerged as candidates in recent years, not as BiV pacing replacements, necessarily, but as additional tools for boosting the efficacy of CRT in more patients.

Randomized trial data on such CRT pacing alternatives have been in short supply. But that supply just ballooned with the release of a second such study, following His-SYNC, that has compared HBP with BiV pacing in patients with heart failure.

In the His-Alternative trial, 50 patients who met strict clinical, echocardiographic, and ECG criteria qualifying them for BiV CRT were randomly assigned to either HBP or BiV pacing as the first-line corrective strategy.

HBP achieved successful and lasting CRT in almost three-quarters of patients in whom it was attempted, including as a backup in one patient with unsuccessful engagement of BiV pacing. The remaining 28% in whom HBP was not successful crossed over to BiV pacing.

All patients in the study achieved successful CRT by one or the other methods, with "His CRT resulting in significant shortening of QRS width and significant improvements in echocardiographic parameters, as well as symptoms and physical capabilities that were comparable to the improvement seen with BiV CRT," said Michael Vinther, MD, PhD, when presenting the trial April 25 during the virtual European Heart Rhythm Association 2021 congress.

"This, however, came at the expense of higher pacing thresholds," said Vinther, from Copenhagen University Hospital Rigshospitalet, referring to a recognized, key HBP limitation.

The higher pacing thresholds needed for HBP to succeed, at least with currently available hardware — 1.8V vs 1.2V for BiV pacing (P < .01) at implantation in the trial, the disparity greater 6 months later — suggests that pulse generators for HBP CRT could potentially need replacement more often, Vinther told | Medscape Cardiology. And more changeouts could mean more infections, among other risks.

"His pacing, as a first-line therapy, is not ready for prime time. As it is now, there are some unresolved issues that we have to address first," he said. But if a left ventricular (LV) lead for BiV pacing can't be positioned sufficiently "to get reasonable thresholds and avoid phrenic nerve stimulation, then His pacing is a really good alternative."

His group's "impression" was that HBP was "at least as effective" as BiV pacing for CRT in the trial's patients, he said, and that is probably enough for either HBP or LBP to be a success in selected patients with heart failure.

"I don't think any of these pacing modalities will be for everybody. There will be patients in whom His bundle pacing will be optimal and patients where biventricular pacing will be the solution," said Vinther, who is also lead author on the study's same-day publication in JACC: Clinical Electrophysiology.

"I think that will be the future. If you start with one strategy and you find out it isn't feasible for one reason or another, you have bailout options with the other strategies," he said.

"I don't think it's going to be one or the other. I think it will be a balance of the two," agreed Niraj Varma, MD, PhD, Cleveland Clinic, who wasn't part of His-Alternative. Both are likely to be more suitable for some patients than others, and in some individuals "it may be a mixture. I can imagine scenarios where we would use a hybrid approach, a left-bundle lead and an LV lead," he told | Medscape Cardiology.

"The signals from His-Alternative confirm impressions from people who do a lot of these cases and from the reported cohort studies. But it's nice to have it from a randomized trial from a prestigious hospital," Varma said.

Much of the published observational His-CRT experience has included patients with failed delivery of the LV lead or who were nonresponders to BiV pacing, he noted. In contrast, His-Alternative entered a "de novo population" with conventional indications for standard BiV CRT. "So that's an advantage."

As invited discussant following Vinther's presentation of the trial, Francisco Leyva, MD, Aston Medical School-Birmingham, United Kingdom, observed that the HBP and BiV pacing groups did not respond differently at 6-month ECG, echo, and functional evaluations by intention-to-treat, but also that HBP seemed to have an edge in the trial's "per protocol" analysis, with signs of more reverse-remodeling than achieved with BiV pacing.

"So, essentially, I think the authors are justified in saying that this could represent an alternative to biventricular pacing," he said. Although further randomized-trial data would be helpful, "as it stands, I think that if one fails to implant a CRT lead, these are quite good data to show that His pacing is a useful alternative."

The single-center His-Alternative trial randomized 50 symptomatic patients in NYHA class 2 to 4 heart failure despite optimal medical therapy, an LV ejection fraction of 35% or less, and in sinus rhythm with left bundle-branch block — defined narrowly by Strauss criteria — to either HBP or BiV pacing as their first-line CRT strategy.

All patients were implanted with standard pacing-only CRT (CRT-P) or defibrillating CRT (CRT-D) systems, except for the substitution of a lead to the His bundle for the LV lead in those assigned to HBP. All patients and clinicians administering the different evaluations were blinded to randomization group.

Seven patients in the HBP group crossed over to LV pacing at the time of implantation, and one patient crossed over from LV pacing to HBP.

Procedure time was greater in patients assigned to HBP than to BiV pacing, with means of 137 min and 102 min (P < .01), respectively. But fluoroscopy times and x-ray dosages didn't differ significantly.

The primary endpoint, successful His-lead implantation with left-bundle capture maintained for 6 months, was achieved by 18 of those patients assigned to HBP, or 72% by ITT.

Ejection fractions rose by 16 points in the HBP group, compared with 13 points for those assigned to BiV pacing. That difference wasn't significant, nor were differences at 6 months in QRS duration, LV end-systolic volumes, natriuretic peptide levels, 6-minute walk distance, or NYHA class — all of which were significantly improved in both groups compared with baseline.

In the per protocol analysis, the mean LV ejection fraction was higher (48% vs 42%; < .05) and LV end-systolic volume lower (65 mL vs 83 mL; < .05) in the HBP group.

When considering only the patients in whom HBP was successfully engaged, Vinther said, "there are indications that they turn out better than with biventricular pacing. But we need more data for this to say if that really holds true."

Vinther and the other authors had no disclosures. Varma has disclosed consulting or speaking for Abbott, Medtronic, Biotronik, Impulse Dynamics, and Boston Scientific. Leyva has disclosed receiving consulting fees and research sponsorship from Medtronic, Boston Scientific, Abbott, Biotronik, and Microport.

European Heart Rhythm Association (EHRA) 2021. Innovative Technology, His pacing as an alternative to Biventricular pacing in symptomatic heart failure patients with left bundle branch block. Presented April 25, 2021.

JACC Clin Electrophysiol. Published online April 25, 2021. Abstract

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