Stroke prevention and the left atrial appendage

 Dhanunjaya Lakkireddy, MD

Dhanunjaya Lakkireddy, MD

I always wondered if the primordial nature of the structure has an intricate connection to the core cardiovascular autonomic nerve enervation.
 

The impact of left atrial appendage (LAA) closure on atrial fibrillation and the function of the left atrium will form the basis of an insightful talk from Dhanunjaya Lakkireddy (University of Kansas Medical Center, Kansas) during this afternoon’s session on protecting the brain in AF. Dr. Lakkireddy will also discuss how neurohormonal modulation is affected by the procedure, beginning by discussing the rationale behind the procedure.

“For most of the strokes that are related atrial fibrillation, the left atrial appendage seems to be the major source of thrombus and subsequent thrombembolization,” he told AF Symposium News. “Then came the concept of ‘Okay, if you exclude the appendage while you are there, either surgically or using a percutaneous approach, you will be able to eliminate the source of thrombus and then subsequently the risk of stroke.’”

Dr. Lakkireddy is especially interested in how this small appendage as a structure, changes cardiovascular physiology. “There are some anecdotal data…that when you get rid of the appendage, the atrial natriuretic peptide levels go down, and then we have fluid retention issues. How is that related to atrial fibrillation? Because if you look at the Cox Maze III procedure for atrial fibrillation, the people who underwent an appendage exclusion in addition to the other lesions are the ones that had the most benefit in terms of rhythm control, and those are the people who have most benefit in terms of stroke prevention.”

These questions led Dr. Lakkireddy and other research groups to investigate further. “I would say we have to categorically divide the function of the left atrial appendage or the pathological connection of the left atrial appendage and the rest of the heart,” he said. “First and foremost, I would say, after the pulmonary vin, the left atrial appendage is the most common source of focus triggers, reentrant phenomena, and other types of arrhythmic contributors.”

He continue: “I think as the substrate evolves from being paroxysmal to more persistent arrhythmia, in a lot of people, especially in women after 70 years of age, there is extensive scarring a fibrosis, and this is what we describe as low atrial myopathy. These are the patients where the left atrial appendage seems to play a much bigger role where in reality pulmonary veins are actually silent. “You almost wonder if, in these people, the left atrial appendage becomes a major contributor to arrhythmia, both by initiating triggers as well as providing enough substrate for the potentiation of the arrhythmia, and thereby cause more and more atrial fibrillation.”

Indeed, some research has already suggested that after pulmonary vein ablation has been carried out, the left atrial appendage seems to have been a source for reentrant arrhythmias that subsequent ablation improves.

“Andrea Natale’s group, with their key paper in Circulation 2010, showed that in at least 30% of people, the left atrial appendage was the only structure that has the triggers and that using it as an additive strategy, in addition to the pulmonary vein isolation has resulted in a dramatic and significant improvement in the overall arrhythmia control,” said Dr. Lakkireddy. 1

Dr. Lakkireddy went on to discuss Lariat procedures, which he began in late 2011. Unlike the closure devices, Lariat procedures involve removing the entire appendage, which may have an effect beyond mechanical occlusion, as he explained: “As a result you eliminate the left atrial appendage from the electrical milieu of the atrium and thereby you are potentially eliminating the sources of reentry. And what you’re also doing is reducing the volume of the left atrium by anywhere between 15 to 30 percent, depending on how large the atrial appendage is to start. Which, in turn, translates into less substrate for arrhythmia propagation and potentiation.”


We found that the recurrence rate in patients who have the combined appendage elimination did much better than those patients who did not have appendage elimination.

With this in mind, Dr. Lakkireddy and his team decided to develop the approach into a more structured therapy to help reduce AF burden. “So that’s what led to what we call the LAALA (left atrial appendata ligation and ablation) AF Registry.2 This was a multicenter prospective observational study where we enrolled patients in a sequential fashion, and we got them in for appendage ligation first followed by atrial ablation, and the we compared them to the conventional approach,” he said. “We found that the recurrence rate in patients who have the combined appendage elimination did much better than those patients who did not have appendage elimination, by at least a 29% reduction in all of their arrhythmia records, which is pretty amazing.”

Dr. Lakkireddy and his team followed these patients up and monitored them for other improvements in outcome. “What we also noticed was a significant drop in their systematic blood pressure. That means their hypertension got better. And we also see that there is also improvement in their overall left atrial volumes. So that kind of suggests, maybe there is something going on by the elimination of the appendage beyond the arrhythmia control itself,” he said. These findings led to the more recent LAA homeostasis study. While the study is yet to be published, Dr. Lakkireddy was able to outline the preliminary results.

“What we have seen is the atrial natriuretic peptide levels come down and then they kind of normalize. We believe the ligation appendage takes over the function and reestablishes the natriuretic and diuretic response,” he said.

The team has also observed other neurohormonal changes, including a drop in epinephrine levels and down regulation in the renin-angiotensin system. For Dr. Lakkireddy, the primitive nature of the left atrium may be a possible explanation. “I always wondered if the primordial nature of the structure has an intricate connection to the core cardiovascular autonomic nerve enervation. Because if you really look at most of the developmental aspects of it, anything that develops so, primordially, early on, has very good connections to a lot of other things that happen.”

Dr. Lakkireddy’s hunch in that the appendage regulates the renin-angiotensin system. “What we’ve noticed is also a significant improvement in the blood pressure control. A lot of people don’t need large doses of antihypertensive therapy anymore,” he explained. Dr. Lakkireddy’s LAA homeostasis study is expected to be published within a few months. He will detail his preliminary results in his talk today.


References

  1. Circulation 2010; 122: 109-118
  2. J Am Coll Cardiol. 2014; 63(12_5)
Tammy Griffin-Kumpey