May 6, 2022 This Week in Cardiology Podcast

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In This Week’s Podcast

For the week ending May 6, 2022, John Mandrola, MD comments on the following news and features stories.

General Comments on the Heart Rhythm Society (HRS) Meeting

Electrophysiology (EP) is a small enough sub-specialty that you get to know people over the years. It felt good to see old friends and colleagues in real life, including a fair number of international friends. On a personal note, I was happy with my talks.

• I debated Vivek Reddy on left atrial appendage occlusion (LAAO). The show of hands at the end revealed the usual: I lost. But the debate was held in the biggest room of the Congress and it was incredibly well attended, which means that many people got to see my slides and the data. It’s the data on percutaneous LAAO that tells the story on why this procedure is a bad idea.

• My second debate was a lot lower key: I took the antagonist the position that atrial fibrillation (AF) ablation should be first line therapy in athletes with AF. My argument here was not that ablation should not be used in athletes, but that we should try other things first, such as risk factor modification, simply waiting, or detraining, and then ablate if AF persists. I have personal experience here in that I had AF during a run-up to a national championship in bike racing, and the Voltaire approach (waiting) worked—my AF slowly dissipated and I avoided thermal energy in my left atrium.

• I gave a brief critical appraisal of the EAST AF net trial (early rhythm control vs standard of care) and proposed what future trials should look like. This was a good session and it made me think about whether we can actually design a study of AF treatment strategies, per se. The problem is that AF is such a diverse condition, affecting young healthy people in much different ways than an elderly person with heart failure with preserved ejection fraction (HFpEF).

• My final talk was on social media, specifically, how to handle disagreements or being wrong on social media. Although I believe in the power of social media, I have too slowly learned some basic lessons:

  • Never argue on Twitter.

  • To persuade, use long-form format, like podcasts and blogs.

  • If you are employed and want to stay employed, avoid politicized issues, such as COVID. Period.

There were no ground-breaking, CABANA-like papers at the HRS meeting. But there was news.

Conduction System Pacing

• Conduction System Disease Recast as Preventive Therapy Target

For my entire career, pacing has been the offensive line of EP; it is necessary but it gets little attention. Catheter ablation has been the quarterback, running back, and receivers. Ablation hogs the attention. But at HRS, pacing made a comeback into the limelight with the rise of conduction system pacing. Three late-breakers addressed the role of placing a pacing lead in the rapidly conducting His-Purkinje system or specialized conduction system.

I have been an early adopter of His bundle pacing (HBP), but now the field has moved on to left bundle branch (LBB) pacing. LBB pacing is easier and produces far better pacing and sensing thresholds. The lead captures the left bundle, or it excites the left bundle early, and this leads to synchronous left ventricle (LV) and right ventricle (RV) contraction, and gorgeous paced QRS complexes.

But until HRS, we had little data. Here are the highlights from HRS.

LBCT LBBP study 1: LBBP-RESYNC was a randomized controlled trial that compared the efficacy of LBB pacing with conventional biventricular pacing in 40 patients with heart failure who were eligible for cardiac resynchronization therapy (CRT). The primary endpoint was the change in LV ejection fraction (EF) from baseline to 6-month follow-up.

• Both pacing techniques improved LVEF from baseline.

• The between group difference in the LVEF was greater in the LBB pacing arm than the biventricular pacing arm by a statistically significant 5.6% (95% confidence interval [CI]; 0.3%-10.9%).

• Secondary endpoints, such as reductions in left ventricular end-systolic volume, NT-proBNP, and QRS duration also favored LBB pacing.

Conduction System Pacing vs Biventricular Pacing. A second late-breaking study, from the Geisinger group, led by Pugazhendhi Vijayaraman, MD, was simultaneously published in Heart Rhythm journal. This was a non-randomized observational study comparing nearly 500 patients eligible for CRT who were treated at two health systems. One group favors conduction system pacing (CSP) and the other does traditional biventricular pacing, which set up a two-armed comparison.

• CSP was accomplished by LBB pacing (65%) and His-bundle pacing (35%).

• The primary endpoint of either death or first hospitalization for heart failure occurred in 28.3% of patients in the CSP arm vs 38.4% of the biventricular arm (hazard ratio [HR] = 1.52; 95% CI, 1.08-2.09).

• QRS duration and LVEF also improved from baseline in both groups.

LBB Area Pacing as a Bailout for Failed CRT. The Geisinger group also presented a multicenter study that assessed the feasibility of LBB pacing as a bailout when standard biventricular pacing did not work, either because of inadequate coronary sinus anatomy or CRT non-response.

• This series included 212 patients for who CRT failed and who underwent attempted left bundle area pacing.

• The bailout was successful in 200 patients (91%).

• The primary endpoint was defined as an increase in LVEF of >5% on echocardiogram.

• About two-thirds of patients had an improvement in LVEF above 5% and nearly 30% had a “super-response.”

• Similar to the previous studies, left bundle pacing resulted in shorter QRS duration and improved echocardiography parameters.

Comments: I know these small randomized controlled trials (RCTs) and nonrandomized comparisons aren’t what we are used to in big drug or device trials. But it’s a start. Here is the take-home:

• Taken together, we learn that LBB pacing appears to increase LVEF similar to CRT and it can be used as a bailout when coronary sinus leads fail.

• This gives me the sense that when RV pacing is expected, LBB pacing is likely to prevent pacing-induced cardiomyopathy.

I am not yet persuaded on clinical outcomes. The first Geisenger study was non-randomized, and you can’t infer that LBB pacing caused the better outcomes because there are likely other reasons (confounders) that led to the LBB group having better outcomes. But these preliminary data give me confidence that we are on the right track, and that there is surely enough equipoise to compare this technique to biventricular pacing. And I think non-inferiority is a fair way to study it, because LBB pacing is less invasive and less costly. And if I have a pacer, I want a LBB lead.

Emergency Triage of AF

• Early Arrhythmia-Specialist Consult, Ordered in the ER, a Boon to AF Outcomes: ER2EP Study

A study from a prominent group of docs addressed the issue of triage of patients who come to the emergency department (ED) because of AF. This is a hugely important topic because oodles of patients with AF meet the healthcare system first in the ED. Some get great care, and some get bad care.

One way to triage these patients is to send them to general medicine or general cardiology. The Kansas City-led group had another idea: let’s give the ED clinicians a hot line to an EP clinician. The ED physicians simply faxed the referral to the EP clinic, "...and then the clinic was basically asked to get the patients in relatively quickly."

The control group received standard care by the ED clinicians with no concerted effort to consult EP. This was a retrospective observational study without randomization. The presenters told us the primary endpoint was time to definitive therapy. (Right off the bat, I hope the modifier “definitive” awoke you.)

Secondary endpoints included major adverse cardiac events (MACE) and bleeding outcomes as well as clinic visits and cardioversions.

There were 200 patients in each group and many differences in baseline characteristics, as you would expect in a non-randomized comparison. Results favored the EP consult group:

• Time to EP evaluation: 1 day for the early consult group vs 128 days for controls;

• Time to ablation: 52 vs 180 days;

• Time to antiarrhythmic drugs (AAD): 3 vs 25 days;

• Time to oral anticoagulation (OAC): 2 vs 17 days;

• Length of stay (LOS): 2 vs 6 days.

Secondary endpoints: The number of hospitalizations and cardiovascular (CV)-related ED visits were lower in the EP consult arm. But the number of clinic visits was not different.

The authors clearly listed the limitations of this study and concluded: “This study provides evidence that having an organized pathway for AF patients can lead to improved outcome times for AF ablation, AAD, OAC and LOS.”

The lead author said this: The findings suggest "a single intervention of appropriate electrophysiologic consultation that is directed from the emergency room" would lead to better outcomes, in part by "mitigating the inherent hurdles in navigating patients through a very complex healthcare system."

Comments: I believe early involvement of EP in patients with AF will lead to benefits. It’s literally what we do. But this study does not come close to showing that our care leads to better outcomes, or less cost. All it shows is that a group of non-randomized AF patients who have a hotline to specialists get more therapy and get it faster.

Even if the study was randomized and had balanced arms, which it wasn’t, all this early intervention is just a surrogate. It may or may or may not be a good thing. For example, for the most important AF treatment, OAC, the difference in initiation of OACs in the two arms was less than 3 weeks. That is hardly clinically relevant.

What’s more, everything about this study is set up to be positive: if you give a busy ED clinician a hotline to a consult, they will be happy to rapidly refer these patients on. Moreover, EP docs are financially and intellectually motivated to intervene, so it’s zero surprise that patients get earlier ablation and more AADs.

And as the authors note, there was more paroxysmal AF in the active arm and more persistent AF in the control arm. Clearly, it’s more likely that paroxysmal AF patients get more AAD and ablation.

Another problem, I went to clincialtrials.gov where scientists are supposed to describe their experiment before the experiment. Here it says there are three primary endpoints, not just one as presented in the late-breaker.

1. Cumulative resource utilization in dollars.

2. Time to definitive therapy (AAD and/or ablation).

3. Number of hospital/clinic visits.

For the first primary endpoint, they presented no data. The second included just AAD and ablation, but in the presentation, they included AAD, ablation, and OAC. And for the third, which they called a secondary endpoint, there was not statistically significant difference. All I will say about this change in endpoints is that it is concerning, especially for a late-breaking clinical trial at a major meeting.

I feel bad being so critical of this study, but if you want to be able to make any conclusions about a therapy pathway, you have to either randomly assign patients or do cluster randomized trials where you randomly assign EDs. And you measure outcomes, not how much therapy someone gets.

To make any positive conclusions from this data is hype--or extravagant promotion. Such conclusions give fodder to the George Bernard Shaw type cynics of medicine.

Cardioneural Ablation

• Can Ablation Abolish Vasovagal Syncope? Early Series Promising

My friends, cardioneural ablation (CNA) could be a huge thing. We have all seen patients with severe bradycardia from excess vagal tone. The most worrisome and difficult patients are those with terrible vasovagal syncope (VVS), who can have pauses of more than 10 seconds and sudden syncope with injury. When this happens to older patients, a pacemaker can help, but not cure, because the vagal surge in VVS involves both severe bradycardia and severe hypotension.

But what happens when such profound bradycardia happens in a 20- or 30-year-old? You don’t want to put pacers in young people.

Well, a few motivated champions have begun to study the use of ablation in the areas of autonomic inputs of the heart. These are located close to the areas we ablate during AF, near the pulmonary veins, but also near the superior vena cava-aorta junction. Right now, there is no billing code for this, and only a few centers are doing it.

At HRS, Rod Tung presented results from a registry of 76 procedures in 13 centers. About two-thirds of the time, CNA was done during another procedure such as AF ablation. The idea here is to reduce the vagal response. This can be measured simply by higher heart rates and less heart rate variability. In fact, many patients who have AF ablation note higher heart rates.

During his presentation, Rod showed examples of HR increases and PR interval shortening during CNA, which is consistent with vagal ablation.

Here is the main result:

• At a median of 8.5 months, 82% were free from syncope after single procedure.

• Five patients underwent repeat ablation.

• Median episodes decreased from 6 to 0, p<0.001.

Dr. Tung’s next slide and comments clearly listed the huge limitations in this case series: non-uniform diagnosis, approach, and endpoints; no control arm, and of course, no one knows for how long vagal denervation will hold.

I have not done this yet, but I am thinking about it. Young patients with profound bradycardia have few good options. If this works and eliminates symptoms without a pacer, it would be a huge advance. But this must be studied in proper form, and that means a sham control randomized trial.

Almost every therapy that has been proposed for VVS has failed to pass muster in a sham-controlled trial. CNA proponents tell me a sham-controlled trial is in the works. Regardless, this is exciting work, and I appreciate the caution expressed in this presentation.

Women in EP

• Why Are Numbers of Women, Minorities So Low in Cardiac EP?

Two studies presented at HRS reported the extremely low numbers of women and underrepresented minorities who practice EP in the United States. Results showed that, on average, 5% of the 3524 EP operators were women. The second study looked at trainees and found very low numbers of women and underrepresented minorities choose to study EP.

It is strange that we have so few women and under-represented minorities in the EP field. I travel in both the cardiology and EP world, and in cardiology, say at the recent ACC meeting, you saw lots of women and minorities. Especially younger ones. Women comprise almost half of my EP group and two of our five interventionalists are women.

EP would seem well suited for work-life balance. We work hard, and think hard, but we don’t do a lot of emergencies. Rare is the “EP-STEMI,” my name for heart block in the ED that needs to come up to the lab for a stat pacer. In 25 years, I have done only three emergent ablations in the early morning hours, all for ventricular tachycardia storm.

I’d love to see more women and minorities in EP. For any listeners who thinking about career choices, you should know that EP is a beautiful field. I cherish it nearly every day. We do procedures and we do doctoring. It’s the best of both worlds because you use your hands and your noggin. And — get this — catheter ablation for atrioventricular nodal reentry tachycardia, Wolff-Parkinson-White syndrome, atrial tachycardia, and some VTs is actually a cure. Tell me how many fields of cardiology can boast cures?

So come join us. It’s a great job, filled up with meaning.