His Bundle Pacing 'Very Viable' Alternative to RV Pacing

John M. Mandrola MD: Hi, everyone. This is John Mandrola from theheart.org and Medscape Cardiology. I'm here at the 2018 American College of Cardiology (ACC) meeting in Orlando, and I'm pleased and delighted to be with two of my friends who are His bundle pacing pioneers. They presented a late-breaking clinical trial today, and I'll have them introduce themselves.

If you anticipate that somebody is going to be paced frequently in the ventricle, His bundle pacing is a very viable first-line option, rather than RV apical pacing.

Pugazhendhi Vijayaraman, MD: Hi. I'm Pugazhendhi Vijayaraman, from Geisinger Heart Institute in Wilkes-Barre, Pennsylvania.

Gopi Dandamudi, MD: I'm Gopi Dandamudi. I used to be at Geisinger, but now I'm at Indiana University School of Medicine. Thank you for having us.

His Bundle Study: Background

Mandrola: Gopi, tell us about the background of this His bundle study.^[1]

Dandamudi: About 10 years ago, we started doing His bundle pacing in patients and started seeing results that were very promising. We gained more experience, and 2-3 years or so after initiating His bundle pacing in our programs, we essentially started doing it in all of our patients.

We decided to compare our results with His bundle pacing with those of our colleagues who were doing right ventricular (RV) pacing specifically at that time about 50 miles away. We had a very protected cohort in rural Pennsylvania—essentially, a population going between the two hospitals. We started collecting a registry of data to look at our experiences versus their experiences.

Vijayaraman: This was one of the largest studies of His bundle pacing that we have done. We looked at all of the patients who had pacemakers implanted from 2013 to 2016, followed up to December 2017. In the hospital where Gopi and I worked, 332 patients underwent His bundle pacing. In the other hospital, every single patient (433 patients) got RV pacing. A total of 765 patients were followed for a mean duration of at least 2 years.

Mandrola: This was a natural comparison, not a randomized comparison?

Vijayaraman: This was not randomized, but they were consecutive patients. Every single patient who required a pacemaker underwent either His bundle or RV pacing on the basis of which hospital they attended.

Baseline Characteristics and Outcomes

Mandrola: Tell us about baseline characteristics and outcomes.

Vijayaraman: Baseline characteristics were fairly similar, reflecting the population. The mean age was about 76 years, and overall, the left ventricular ejection fraction was 54% in both groups. Thirty-five percent of patients had sinus node dysfunction, and 65% of patients had atrioventricular (AV) nodal dysfunction. In the His bundle pacing group, there was a slightly higher incidence of males, a higher incidence of atrial fibrillation, and slightly more use of beta-blockers.

During follow-up, the primary outcome of the study was a composite endpoint of death from any cause, first episode of heart failure (HF) hospitalization, or upgrade to biventricular (BiV) pacing. Incidence of the primary outcome was significantly reduced in the His bundle pacing population (25%) compared with the RV pacing population (32%). Relative risk reduction was 29%, with a hazard ratio of 0.71.

Subgroups and Limitations

Mandrola: Were there any specific subgroups that interested you?

Vijayaraman: We looked at the secondary endpoints for both HF hospitalization and mortality. More important, what was essential in this group was the amount of pacing. Anyone who got > 20% ventricular pacing showed a significant difference in terms of the outcomes. For those who got < 20% pacing, there was no difference between the groups, suggesting that it was RV pacing-induced worsening of outcomes.

Mandrola: Gopi, because this was a nonrandomized comparison, aren't there are some limitations?

Dandamudi: These were not carefully controlled cohorts. These were all-comers—consecutive patients. Of note, they essentially balanced each other out for patient characteristics, except for the subtle differences that were mentioned earlier. What is more powerful about this study is that the mean follow-up was about 2 years.

These were all preserved LV systolic function patients to begin with. We were seeing such magnitude of differences within 2 years in preserved LV systolic function patients with pacing above 20%. All cohorts of patients who had < 20% of pacing, whether His bundle or RV pacing, had similar outcomes. Even patients who were paced at a higher degree with His bundle pacing had similar outcomes. Patients with > 20% of pacing from the RV clearly had worse outcomes from a HF standpoint.

Mandrola: If you have patients with good ventricular function at baseline, it would be hard for His bundle pacing to reduce outcomes, yet it did. That is pretty remarkable, isn't it?

Dandamudi: Even patients who had His bundle pacing had adverse outcomes (they did meet primary endpoints), but the degree of progression probably is significantly reduced. Again, these are elderly cohort patients who are going to have other risk factors and comorbidities that increase their risk. Other trials,^[2] such as BLOCK HF and BioPace, also had significant events. If you look at BLOCK HF^[3] specifically, within the first 6-7 months or so, 30% or more of patients who had BiV pacing met their primary endpoint of either HF, increase in LV systolic dimensions, or even mortality. Clearly, these patient cohorts are prone to HF, but the degree of HF to which they develop with pacing is substantially mitigated with His bundle pacing, compared with RV pacing.

Can These Results Be Replicated in the 'Real World'?

Mandrola: Puga, you mentioned in the publication that these were experienced operators. Naysayers might say, "We can't really replicate this in the real world, and this is too difficult to do." What do you say about that?

Vijayaraman: That's a great point, John. In that group, three implanters did the His bundle pacing. I started quite early, and Gopi started a few years after, so we had experience by the time we did the study.

We have another operator in the study who came out of fellowship and contributed close to 15% of the population. He was able to do His bundle pacing with the same degree of success as the rest of us. Although he might take a little longer, it's doable.

You've been doing His bundle pacing for a fair amount of time. How much time did you need to learn His bundle pacing?

Mandrola: The audience needs to know that I'm quite biased and so impressed by His bundle pacing. I was able to pick it up after 5 or 10 cases, and I've done about 100 cases. It's a beautiful technique, and now that we have some outcomes data, it's even better.

Gopi, what are the clinical implications of this? Where do we go from here?

Clinical Implications of His Bundle Pacing

Dandamudi: Again, I want to emphasize that this was not a randomized trial. This was clearly a cohort trial with an observational study design. We definitely need randomized trials to control for the variables and get real data so we can look at this more carefully. We are convinced at this point that with all of our smaller data sets plus other published results, we would expect to see significant differences between RV pacing and His bundle pacing.

We are trying to work with the National Institutes of Health to develop a trial looking at overall outcomes of RV pacing versus His bundle pacing in patients who require > 20% of pacing over for a prespecified time period of about 5 years.

What Are the Concerns?

Mandrola: What are some of the concerns? Why do we even need a trial?

Vijayaraman: Apart from showing that it is feasible and improves outcomes, there are some limitations of His bundle pacing. Because of the location of the lead in fibrous tissue, lead revision rates are a little bit higher; in this study it was about 4%. We want to emphasize that whereas only two patients developed lead dislodgment and loss of capture, most patients had progressive increase in threshold. It was relatively safe to follow them and revise the lead at a safe time rather than waiting for it to fail.

We need improvement in technology, both with lead devices and delivery tools, so we can make it closer to 100% successful.

We need improvement in technology, both with lead devices and delivery tools, so we can make it closer to 100% successful. A randomized trial would give us a much more fair comparison of the two groups, in terms of safety outcomes and feasibility.

Mandrola: Lead dislodgement is one issue; high thresholds is another. The implication here is that if the threshold is high, you might need to do more generator changes, and generator changes may have a higher risk. Is that a reasonable criticism?

Dandamudi: Absolutely. It's important for us to understand that when you compare RV pacing versus BiV pacing, we see similar differences as well where the thresholds can be high with LV pacing. To some degree, we feel that RV pacing versus His bundle pacing is not really a fair comparison, because you're talking about myocardial pacing versus something different entirely. A more apt comparison would be BiV pacing, where you are getting LV upper cardiac pacing, versus His bundle pacing, which is again a fibrous tissue that you are trying to penetrate and actually capture.

Just as BiV pacing evolved over the past 15 years with better battery and lead technology, it's very important for us to realize that we are dealing with very obsolete technology, in terms of a single lead and a single sheath. We are hopeful that as industry spends more developing better tools, delivery systems, leads, and devices, some of these negative aspects of His bundle pacing can be easily overcome.

Mandrola: Yes, that is a good point, because I think the young guys who are doing cardiac resynchronization therapy (CRT) now do not really realize that when we first started doing CRT, there were no over-the-wire leads and it was really difficult. Like you said, with His bundle pacing, we have one sheath and one lead.

Dandamudi: I always joke that to do a fair comparison, you should do it with LV pacing using a single sheath and a single lead and that will give you a bipolar lead rather than a unipolar lead, versus His bundle pacing with the current tools, to really see the success rates as well as pacing thresholds.

Special Populations

Mandrola: Another concern is that if you are pacing the His bundle in patients who are older and have heart disease, what about the risk of developing a block below that level? Of course, if you do not have a backup lead, that is trouble.

Vijayaraman: We do have data on some of these patients. We have been doing this for more than 10 years, and we have follow-up data on some of those patients during generator change. We noticed that the incidence of any new His-Purkinje disease in these patients is no different. They do not develop progression of conduction disease because you put a lead in the His bundle.

We find that with a good number of patients who have infranodal disease in the His-Purkinje system, the progression is more transverse than longitudinal. If you get good results acutely, they tend to stay relatively stable, even during medium-term follow-up. That is something to look into as we do further studies.

Dandamudi: It's also important to realize that for the vast majority of the time, we are getting nonselective His bundle pacing. We are actually getting local myocardial capture at the same time as we are getting His bundle capture. That usually serves as your backup. Essentially, you are achieving both septal pacing and well as His bundle pacing at the same time, with very minimal fusion. In case you do develop progressive conduction system disease, we think that you are getting local septal capture as a backup.

Vijayaraman: That's a great point. In this study of 332 patients with His bundle pacing, 62% of them had nonselective His bundle pacing, which means they had both His bundle and RV capture. You get two for one.

Mandrola: Meaning that even if the His-bundle develops block below there, you still have some local ventricular capture.

Final Thoughts for the Referring Cardiologist

Mandrola: Knowing what we know now about His bundle pacing, what do you say to general cardiologists who are referring patients to electrophysiologists for pacing?

Vijayaraman: One of the lessons we have learned from this is that it's better to prevent HF than to treat it after it develops. By doing His bundle pacing, we are preventing development of pacing-induced cardiomyopathy. We also find that the chance to upgrade these patients is a lot harder once they develop HF, so try for His bundle pacing from the beginning, so we can avoid heart pacing-induced HF.

Dandamudi: There are enough data now to support, at least with RV pacing versus His bundle pacing, that if you anticipate somebody is going to be paced frequently in the ventricle, His bundle pacing is a very viable first-line option, rather than RV apical pacing.

Mandrola: Excellent. It's been great having you. Thank you very much.

Vijayaraman: Thank you very much.

Dandamudi: Thank you for having us.

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