The Three Big Stories From HRS 2021

The partially in-person 2021 Heart Rhythm Society (HRS) scientific sessions had two themes: one optimistic, the other sobering.

Always start with the positive. When I asked colleagues for their most important take-home from HRS, one message stood out: "People saw each other. Live."

We all know the upsides of virtual meetings. But virtual meetings cannot replace the main reason for medical conferences: meeting with colleagues. I have a strong sense that discussions among colleagues over coffee or dinner improve patient care as much or more than any lecture or new catheter.

The images of people roaming the Boston convention center were extremely hopeful.

Now the sobering part. Medical progress is super hard, and this year's HRS proved it.

Despite 16 late-breaking clinical trials and more than a thousand original papers, I saw no major developments for electrophysiology (EP).

The main barrier for innovation in EP is our incredible success over the past two decades. And it's not only the field of EP that has progressed; stopping a myocardial infarction with percutaneous coronary intervention before it damages the ventricle and the availability of four classes of medicines that improve the ventricle after it has been damaged has shrunk the pool of patients that can benefit from our devices.

The other major headwind to progress is that the most common arrhythmia, atrial fibrillation, remains shrouded in mystery.

Can you imagine that in 2021, we do not know the cause of AF? Is it due to multiple wavelet reentry (1964) or focal firing (1959)? Inquisitive patients with AF sometimes ask, 'Doc, how do you know where to burn?' Short answer: we don't.

Is Pulsed Field Ablation the Next Big Thing?

One of the hottest topics at HRS was a new nonthermal way to destroy cardiac cells called pulsed field ablation (PFA). It works via electroporation, a technique that involves applying electrical current to the heart, which then disrupts current flow across the cardiac cell membrane. This results in pore formation and cell death.

The main upside of PFA is its cardioselectivity; it does not harm the adjacent phrenic nerve or esophagus. It's also fast. Rapid electrical isolation of pulmonary veins means patients require less anesthesia.

Faster, safer AF ablation might seem like a huge advance, and it could be. But the one sure thing I have learned from going to AF meetings the past 20 years is that what seems amazing in early trials often fizzles out. Think rotor mapping.

Pulsed field ablation faces two high hurdles: one is that it doesn't explain AF, it merely allows more ablation in the left atrium.

The current practice for AF ablation is to simply isolate the pulmonary veins. The practice is both evidence-based and pragmatic. With PFA, it will be easier to do more ablation, and I predict there will be a move to add ablation to the other areas of left atrium. Whether this helps improve quality of life and reduce AF episodes or stroke remains an open question.

You might think more ablation translates to a greater chance of reducing AF. But it's also possible that more ablation will lead to more atrial flutters or less atrial contraction — which might impede cardiac output or increase the risk for stroke.

The second hurdle for PFA is safety. Although cardioselectivity will prevent esophageal and phrenic damage, there is a concern over brain lesions. Intracardiac echo reveals that PFA in the left atrium causes immediate and intense microbubble formation. David Tomlinson and I expressed this concern in an editorial in the Journal of the American College of Cardiology. We noted the dearth of brain MRI assessments in patients undergoing PFA for persistent AF.

An abstract presented at HRS by Prof Andrea Natale reinforced the concern of brain injury during PFA. Using transcranial Doppler to monitor the burden of cerebral microemboli signals in six patients undergoing AF ablation, Natale and co-workers found that PFA "generated a relevant number of microemboli signals frequently clustered in short-lasting shower-like patterns."

Before I had PFA ablation on my left atrium, I would want to see a large series of studies chronicling post-PFA MRI scans.

Two companies will develop PFA delivery systems. Marketing will be intense. The FDA is increasingly lax. Critical appraisal will be left to electrophysiologists. Are we up to the challenge?

LBB Area Pacing

The other hot topic at HRS was left bundle branch area pacing, an evolution of His-bundle pacing.

His-bundle pacing works because it recreates normal conduction and results in simultaneous activation of both right and left ventricles. This can prevent pacing-induced cardiomyopathy as well as serve as a cardiac resynchronization device in patients with left bundle branch block. His-bundle pacing also creates stunningly beautiful ECG patterns of narrow-paced QRS complexes, and the aesthetics should not be underestimated.

The problem with His-bundle pacing is that it is hard to do, it's associated with more lead revisions, and its higher pacing thresholds mean shorter battery life.

LBB pacing arose because of these downsides. The idea is to place the lead a few centimeters south of the His bundle on the right ventricular septum, then screw the thin pacing lead into and through the septum to capture the left bundle branch. You can actually see it penetrate the septum on x-ray.

If you get the lead tip to the left bundle or even close, then you prevent delayed LV activation. LBB area pacing has been shown to have far better pacing and sensing thresholds — which means better longevity and less lead revision.

But questions remain about the long-term function of the lead. Being burrowed into the septum creates a fulcrum, and over time, that might cause late lead failures. I can also testify that LBB area pacing has a learning curve.

My senior partner asked me the important question: "Mandrola, all this fancy stuff you are doing, is it worth it?" He knows I love evidence and randomized controlled trials, and so he asked me the question: do you have any evidence that this new technique is better than the standard?

HRS featured a late-breaking study with a promising title: "Clinical Outcomes of Left Bundle Branch Area Pacing Compared to Right Ventricular Pacing." But the next part of the title induced a bit of worry: "Results From the Geisinger-Rush Conduction System Pacing Registry."

The groups at Rush University and Geisinger Health System pooled outcome data on patients who received LBB area pacing or RV pacing. Their primary endpoint was the composite of death, heart failure hospitalization, and the need for upgrade to a biventricular device. About 300 patients were in the two groups.

LBB pacing crushed RV pacing. Over 3 years, it reduced the composite primary outcome by 54%.

The fatal flaw was that the groups were not randomized. A doctor decided to implant either an LBB area lead or a standard lead. Although there were few differences in baseline characteristics, there was surely selection bias, with sicker patients receiving standard RV leads. How do I know that? Because there was a near 50% reduction in death with LBB area pacing. No proponent of this technique would be so bold to suggest that the location of a pacing lead would halve the risk for death over 3 years.

I have friends who were involved in this study and I don't want to make them mad, but nonrandomized comparisons like this will never be able to answer the outcome question. Registry data can tell us what we are doing: how many cases, how many complications? But it cannot be used to compare outcomes. For this, you need randomization of the two groups.

Alas, a problem with the current model of medical evidence in cardiology is our heavy reliance on industry for funding. That works well when there is a confluence of interests. In the case of LBB area pacing, like His-bundle pacing, there is no confluence because these techniques would reduce the number of pricey biventricular devices, leaving industry no incentive to fund a proper trial. That's not nefarious; it is just the current model.

Conclusion

Although one may find it sobering that the two major areas of innovation in our field are so nascent, progress in science is often asymmetric and unexpected. There is always hope.

In the meantime, we can celebrate an in-person meeting and the smaller incremental gains that contribute to making electrophysiology a field with ample tools to help people. And for these, I remain grateful.

John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence.

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