Closing the Left Atrial Septal Pouch For Stroke Prevention Explored in Small Trial

Using a patent foramen ovale (PFO) occluder to pinch off the left atrial septal pouch (LASP) is feasible and may lessen the risk of recurrent cerebrovascular events in patients with cryptogenic stroke, a small, single-center, randomized trial suggests.

After a year-and-a-half of follow-up, brain MRI revealed de novo embolic lesions in five patients treated with antiplatelet therapy alone and in none who had the LASP eliminated using the transcatheter procedure (P = 0.018), Chaowu Yan, MD, PhD, and Hua Li, MD (both from Fuwai Hospital, Beijing, China), report in a research letter published this month in JACC: Cardiovascular Interventions.

“This preliminary study suggests that transcatheter LASP elimination is clinically feasible and safe,” Yan told TCTMD via email. “Although controversy remains regarding the role of the LASP itself as an independent risk factor for cryptogenic stroke, our study supported that it was the cause of cardiac embolism.”

He added, however, that this “novel procedure is still in clinical trials, and it should not be used widely at the current time.” Additional research is also needed, Yan said, to compare antiplatelets and anticoagulants for secondary stroke prevention in patients with a LASP.

The left atrial septal pouch, which occurs when the septum primum and septum secundum at the interatrial septum fail to completely fuse and is found in 30% to 35% of all adults, was first described about 14 years ago in an autopsy study by Subramaniam Krishnan, MD (now with Sutter Heart & Vascular Institute, Sacramento, CA), and Miguel Salazar Jr, MD (now with Adventist Health, Los Angeles, CA), with a subsequent publication showing thrombus in this pouch in three patients.

“Around that time,” Krishnan told TCTMD, “there was a lot of excitement in electrophysiology and interventional cardiology with innovations happening with the left atrial appendage, and it seemed to me that [the LASP] is another structure that similarly behaves like a cul-de-sac, and it also has a potential to form blood clots and strokes.”

Since then, there have been numerous studies confirming that thrombus can form in the LASP and that patients with cryptogenic strokes or embolic stroke of undetermined source (ESUS) are much more likely than people in the general population to have such a pouch.

Now, “I think this paper from Beijing, China, is going to stimulate research in this field in a very big way,” Krishnan predicted, adding, “I think it’s very important to show that you can indeed completely eliminate or obliterate the septal pouch with a conventional septal occluder device. That by itself is an important finding.”

Transcatheter LASP Elimination

In the current study, Yan and Li tested the “clinically reasonable” hypothesis that using a PFO closure device to eliminate a LASP is both feasible and potentially associated with a lower risk for recurrent stroke. At their center, they randomized 60 patients (mean age 44 years; 58% men) who had a cryptogenic stroke and LASP (identified on contrast transesophageal echocardiography and confirmed with multislice CT) to antiplatelet therapy with or without transcatheter elimination of the pouch.

For all patients, a team of cardiologists, neurologists, and imaging specialists determined that the initial stroke was more likely to be associated with the presence of the LASP than other potential causes.

The LASP elimination procedure was performed using a transseptal puncture and implantation of a 30/30-mm, double-disc PFO occluder (Cardi-O-Fix; Starway Medical Technology) to clamp the pouch closed. All procedures were successful, with no complications; repeat multislice CT confirmed LASP elimination.

The investigators repeated brain MRI every 3 to 6 months over the 18-month follow-up and found de novo embolic lesions only among patients who were treated with antiplatelet therapy alone.

Commenting for TCTMD, Arnold Seto, MD, MPA (VA Long Beach Healthcare System, CA), said the investigators were “brave” to complete this trial, conducted before LASPs have been shown to be a proven source for stroke. He added that it “at least will probably serve as a basis for a larger study as people accumulate more evidence and also attract more interest” around researching the importance of LASPs.

‘Potentially Unmet Need’

These pouches may be a cause of cardioembolic stroke and represent a “potentially unmet need that we aren’t addressing by screening for A-fib and closing PFOs,” Seto said. “That’s why this topic is pretty exciting.”

Since LASPs were only first described in 2010, it will take some time to accumulate the necessary evidence to establish a definitive association between these findings and stroke, which is needed to justify larger trials evaluating potential interventions, he suggested, noting that it took decades for the field of PFO closure to evolve.

For now, clinicians need to learn about LASP and its potential implications, Seto said. “It begins by educating ourselves as cardiologists and educating our noninvasive colleagues about what the structure looks like, what it is called, and then to follow that association with subsequent stroke.”

Seto credited Krishnan with introducing the idea that the LASP is a potential source for stroke, which is “definitely a concept that requires more investigation. I think it’s an exciting potential for answering the still stubborn question of: what’s the cause of the cryptogenic stroke?”

Krishnan said part of the reason the LASP hasn’t gained as much attention as the left atrial appendage (LAA) as a potential stroke source is that LAAs are present in everybody and LASPs are not. And although blood clots in LASPs are being increasingly described in the literature, they are not as common as clots in LAAs, possibly because there is a mechanism preventing them. “Brisk flow from the right pulmonary veins acts as a protective mechanism. It prevents stasis of blood,” he explained. “And when you lose that protective mechanism, we propose that blood clots will start to form with increasing frequency.”

Mitral stenosis, perhaps related to rheumatic heart disease, and congestive heart failure are two conditions that might lead to the loss of this protective blood flow past the LASP and increase the chances of a clot, he pointed out.

Krishnan said he and some other researchers have reached out to companies that make septal occluder devices to gauge interest in a prospective, multicenter study of LASP elimination in patients with ESUS, a condition in which the risk of recurrent stroke is 5% per year.

While waiting for such a study to materialize, the take-home message for clinicians, particularly cardiologists and stroke neurologists, is that “they have to be aware of this anatomical entity,” Krishnan said. “And in patients who present with cryptogenic strokes, similar to PFOs, this is a structure that must be looked for.”

Indeed, Yan said, “in clinical practice, more attention should be paid to the detection of LASP among patients with cryptogenic stroke. Currently, there is no consensus on the management of LASP and a personalized approach might be warranted.”