Thrombus Relatively Common After LAA Occlusion With Amplatzer Amulet, Small Study Suggests

Device-related thrombus was found in about 17% of A-fib patients undergoing left atrial appendage (LAA) occlusion with the Amplatzer Amulet device in a small, single-center study, raising questions about whether the routine use of dual antiplatelet therapy (DAPT) after implantation is sufficient.

Of the four patients with thrombus detected, three were still taking DAPT and one was on clopidogrel monotherapy after a planned stoppage of dual therapy, lead author Alexander Sedaghat, MD (University of Bonn, Germany), and colleagues report in a study published online July 27, 2016, ahead of print in JACC: Clinical Electrophysiology.

Senior author Christoph Hammerstingl, MD (University of Bonn), told TCTMD that he was somewhat surprised by how high the rate of thrombus was with the Amplatzer Amulet device, noting that a prior study of the older Amplatzer Cardiac Plug (both St. Jude Medical) showed a similar rate. The newer device comes with features meant to reduce thrombogenicity.

Hammerstingl said that the thrombogenicity of the Amulet device itself is probably not much different compared with other occluders, including the Watchman device (Boston Scientific), which has been shown to have a much lower rate of device-related thrombus (about 5.7%). That difference, he said, is likely related to the types of antithrombotic therapy recommended after implantation: warfarin followed by DAPT for the Watchman and DAPT alone for the Amulet.

He pointed out that antiplatelet therapy alone has been shown to be ineffective in patients with A-fib. “I would say it’s not the right decision to choose dual antiplatelet treatment alone and not introduce something like low-dose oral anticoagulants,” Hammerstingl suggested.

Commenting on the study for TCTMD, Jacqueline Saw, MD (University of British Columbia, Vancouver, Canada), said she, too, was surprised at the high rate of thrombus in the study, pointing to larger series from other centers showing rates of device-related thrombus of 4% or lower.

She said that she’s attuned to data regarding the Amplatzer devices, as well as the Watchman, because she serves as a consultant/proctor for both manufacturers and as chair of the events committee for the Amplatzer Amulet Post-Market Study.

“My concern about this study is that it’s not reflective of the overall experience that we’ve seen in other centers,” Saw said.

Also commenting on the study, Réda Ibrahim, MD (University of Montreal, Canada), agreed, putting the rate of device-related thrombus at less than 5%.

Both Saw and Ibrahim questioned whether implantation technique was adequate in the study. Saw said that because all of the procedures were performed under conscious sedation, it is unlikely TEE was used during the procedure to guide placement of the device.

Ibrahim noted that the rate of incomplete LAA sealing was 100% in the patients with thrombus and 41.2% in those without thrombus. The rate depends on how incomplete closure is defined, but he said it has been below 10% in his experience.

Saw and Ibrahim both stressed the need for optimal implantation technique to minimize peridevice leak and thrombus formation and Ibrahim said that patients should be followed up systematically with transesophageal echocardiography (TEE).

The Amulet device holds CE Mark in Europe but is not US Food and Drug Administration approved. The company expects to start the trial required for US regulatory approval before the end of the year.  

Oral Anticoagulation Resolves Thrombi

The study included 24 patients who underwent LAA occlusion with the Amulet device between November 2014 and November 2015. Patients had high risks of thromboembolic events (mean CHA₂DS₂-VASc score of 4.3) and bleeding (mean HAS-BLED score of 3.6). The indication for occlusion was a history of bleeding in 75% and an anticipated high bleeding risk in the rest.

Occlusion was successful in all patients, although two had periprocedural complications, including minor pericardial effusion in one and pericardial tamponade with the need for pericardiocentesis in the other.

All but one patient, who chose to take oral anticoagulation, were prescribed DAPT for at least 3 months after the procedure.

The thrombi in four patients were detected by TEE an average of 11 weeks after the procedure, prior to electrocardioversion in one patient and during routine follow-up in the remainder.  “All thrombi were observed within the untrabeculated region of the LAA ostium between the left upper pulmonary vein ridge and the occluder disc, indicating suboptimal LAA occlusion,” the authors write.

Baseline echocardiography revealed that patients who eventually developed device-related thrombi had higher degrees of spontaneous echo contrast grades within the LAA (3.0 vs 1.3), lower LAA peak emptying velocities (17.5 vs 48.3 cm/s), and lower LVEF (39.0% vs 50.0%). They also were more likely to have a history of LAA thrombi (75.0% vs 19.2%).

Physicians initiated direct-acting oral anticoagulants (DOACs)—apixaban (Eliquis; Bristol-Myers Squibb) and edoxaban (Savaysa; Daiichi Sankyo) in one patient each and dabigatran (Pradaxa; Boehringer Ingelheim) in two—for treatment, and follow-up TEE performed an average of 6 weeks later showed that all thrombi had been resolved.

The Dilemma

“The presented data underline the unmet need to define an optimized postprocedural anticoagulant regimen after LAA [occlusion],” the authors write.

The relatively high frequency of device-related thrombus creates a dilemma for physicians, given that many patients undergoing LAA occlusion are doing so because of a prohibitive risk of bleeding with oral anticoagulation and the presence of thrombus represents an indication for anticoagulation, they say.

Hammerstingl acknowledged that there is no definitive evidence that these device-related thrombi are actually causing clinical events, but said he would expect rates of stroke and cerebral embolism to be higher in patients with such a finding, necessitating the use of oral anticoagulation.

Ibrahim disagreed that anticoagulation should be routinely considered in these patients, however, because most are referred for LAA closure because of a high bleeding risk.

If the rate of thrombus actually is as high as seen in this study, “we should recommend anticoagulation,” Ibrahim said, “but so far we have no signal that we need to anticoagulate the patients, especially because they are typically difficult patients to anticoagulate when they are referred.”

Saw also did not see justification for a move to postimplant anticoagulation, and said DAPT should still be used as recommended.

“We can’t hang our hat on just a small, single-center registry where there’s some question about the implant’s technical success and periprocedural monitoring of the device implant,” she said. “So we need to look at larger studies.”

The researchers agree that further studies are warranted.

“Given the limited patient number included in this analysis, large-scale randomized studies are needed to further address this topic and general recommendations cannot be given at this point,” they write. “However, when device-related thrombi are encountered on the Amulet device, a temporary regimen of DOAC appears to be safe and effective, at least in selected patients.”

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