Taking Cardiac Pacing From Boring to Super-Cool

For the past two decades, catheter ablation stole most of the excitement in electrophysiology. Cardiac pacing was seen as necessary but boring. His-bundle pacing earned only modest attention.

But at the Heart Rhythm Society (HRS) 2022 scientific sessions in San Francisco, cardiac pacing consolidated its comeback and entered the super-cool category.

Not one but three late-breaking clinical trials considered the role of pacing the heart's conduction system for both preventive and therapeutic purposes. Conduction system pacing, or CSP as we call it, includes pacing the His bundle or the left bundle branch. Left bundle-branch pacing has now largely replaced His-bundle pacing.

Before I tell you about the studies, let's review why CSP disrupts the status quo.

The core idea goes back to basic physiology: After the impulse leaves the atrioventricular node, the heart's specialized conduction system allows rapid and synchronous conduction to both the right and left ventricles.

Standard cardiac pacing means fixing a pacing lead into the muscle of the right ventricle. From that spot, conduction spreads via slower muscle-to-muscle conduction, which leads to a wide QRS complex and the right ventricle contracts before the left ventricle.

While such dyssynchronous contraction is better than no contraction, this approach leads to a pacing-induced cardiomyopathy in a substantial number of cases. (The incidence reported in many studies varies widely.)

The most disruptive effect of conduction system pacing is that it is a form of cardiac resynchronization therapy (CRT). And that is nifty because, until recently, resynchronizing the ventricles required placing two ventricular leads: one in the right ventricle and the other in the coronary sinus to pace the left ventricle.

Left Bundle-Branch Pacing vs Biventricular Pacing

The first of the three HRS studies is the LBBP-RESYNC randomized controlled trial led by Jiangang Zou, MD, PhD, and performed in multiple centers in China. It compared the efficacy of left bundle-branch pacing (LBBP) to that of conventional biventricular pacing in 40 patients with heart failure who were eligible for CRT. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to 6-month follow-up.

The results favored LBBP. Although both pacing techniques improved LVEF from baseline, the between-group difference in LVEF was greater in the LBBP arm than the biventricular pacing arm by a statistically significant 5.6% (95% CI, 0.3% - 10.9%). Secondary endpoints, such as reductions in left ventricular end-systolic volume, N-terminal pro–brain natriuretic peptide, and QRS duration, also favored LBBP.

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.

This nonrandomized observational study compared nearly 500 patients eligible for CRT treated at two health systems. One group favors conduction system pacing and the other does traditional biventricular pacing, which set up a two-armed comparison.

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

The primary endpoint of 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, 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 and published an international multicenter study that assessed the feasibility of LBBP as a bailout when standard biventricular pacing did not work—because of inadequate coronary sinus anatomy or CRT nonresponse, defined as lack of clinical or echocardiographic improvement.

This series included 212 patients in whom CRT failed and who underwent attempted LBBP pacing. The bailout was successful in 200 patients (91%). The primary endpoint was defined as an increase in LVEF above 5% on echocardiography.

During 12-month follow-up, 61% of patients had an improvement in LVEF above 5% and nearly 30% had a "super-response," defined as a 20% or greater increase or normalization of LVEF. Similar to the previous studies, LBBP resulted in shorter QRS duration and improved echocardiography parameters.

Am I Persuaded?

I was an early adopter of His-bundle pacing. When successful, it delivered both aesthetically pleasing QRS complexes and clinical efficacy. But there were many challenges: it is technically difficult, and capture thresholds are often high at implant and get higher over time, which leads to shorter battery life.

Pacing the left bundle branch mitigates these challenges. Here, the operator approaches from the right side and screws the lead a few millimeters into the septum, so the tip of the lead can capture the left bundle or one of its branches. This allows activation of the heart's specialized conduction system and thus synchronizes right and left ventricle contraction.

Although there is a learning curve, LBBP is technically easier than His-bundle pacing and ultimately results in far better pacing and sensing parameters. What's more, the preferred lead for LBBP has a stellar efficacy record—over years.

ECG after CSP showing right bundle-branch pattern in V1, rapid activation in V6, and narrow paced QRS complexes.

I have become enthralled by the gorgeous QRS complexes from LBBP. The ability to pace the heart without creating dyssynchrony infuses me with joy. I chose cardiology largely because of the beauty of the ECG.

But as a medical conservative who is cautious about unproven therapies, I have questions. How is LBBP defined? Is left septal pacing good enough, or do you need actual left bundle capture? What about long-term performance of a lead in the septum?

Biventricular pacing has set a high bar because it has been proven effective for reducing hard clinical outcomes in large randomized controlled trials.

The studies at HRS begin to answer these questions. The randomized controlled trial from China supports the notion that effective LBBP (the investigators rigorously defined left bundle capture) leads to favorable effects on cardiac contraction. The two observational studies reported similarly encouraging findings on cardiac function.

The three studies therefore tentatively support the notion that LBBP actually produces favorable cardiac performance.

Whether LBBP leads to better clinical outcomes remains uncertain. The nonrandomized comparison study, which found better hard outcomes in the CSP arm, cannot be used to infer causality. There is too much risk for selection bias.

But the LBBP bailout study does suggest that this strategy is reasonable when coronary sinus leads fail—especially since the alternative is surgical placement of an epicardial lead on the left ventricle.

At minimum, the HRS studies persuade me that LBBP will likely prevent pacing-induced cardiomyopathy. If I or a family member required a pacemaker, I'd surely want the operator to be skilled at placing a left bundle lead.

While I am confident that conduction system pacing will become a transformative advance in cardiac pacing, aesthetically pleasing ECG patterns are not enough. There remains much to learn with this nascent approach.

The Barriers to Getting More CSP Trials

The challenge going forward will be funding new trials. CSP stands to prevent pacing-induced cardiomyopathy and offer less costly alternatives to standard biventricular pacing for CRT. This is great for patients, but it would mean that fewer higher-cost CRT devices will be sold.

Heart rhythm research is largely industry-funded because in most cases better therapies for patients mean more profits for industry. In the case of CSP, there is no such confluence of interests.

Conduction system pacing has come about because of the efforts of a few tireless champions who not only published extensively but were also skilled at using social media to spread the excitement. Trials have been small and often self-funded.

The data presented at HRS provides enough equipoise to support a large outcomes-based randomized controlled trial. Imagine if our CSP champions were able to find public-funding sources for such future trials.

Now that would be super-cool.

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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