Use of the Lariat device to occlude the left atrial appendage (LAA) carries a marked risk of serious complications, according to an analysis of published studies and adverse event reports released online May 4, 2015, ahead of print in JAMA Internal Medicine.

The safety signal is all the more concerning, say Jay Giri, MD, MPH, of the Hospital of the University of Pennsylvania (Philadelphia, PA), and colleagues, because it arises from off-label use of a device that carries FDA approval predicated on its similarity to devices used for surgical tissue ligation. Based on the reported data, “high-quality randomized clinical trials examining the Lariat as a device for LAA exclusion should be obtained before its widespread use is adopted by the medical community,” they contend.

The researchers reviewed the medical literature from January 2007 through August 2014 and the FDA MAUDE database of adverse events over almost the same period for details on procedural outcomes following use of the Lariat snare system (SentreHEART; Redwood City, CA).

“All reported instances of Lariat use in the medical literature were for the indication of LAA exclusion,” they note.

In 5 studies involving 309 patients, procedural success—defined as successful closure of the LAA during the index procedure—was 90.3%. Cardiac surgery was urgently needed in 2.3% of patients and 0.3% died in the hospital.

Pericardial Effusion Cited as a Problem

From January 2007 through July 2014, the MAUDE database contained 35 unique reports of adverse events:

• Pericardial effusion and in-hospital death (n = 5)
• Pericardial effusion with need for urgent cardiac surgery (n = 22)
• Need for urgent cardiac surgery (no mention of pericardial effusion; n = 1)
• Urgent placement of a drain to address pericardial effusion (n = 7)

Procedural success for the cases involving these adverse events was 35.5%, with 4 cases unable to be characterized based on the report.

The majority of complications were attributed, in similar proportions, to either the magnetic wires used for device deployment (40.0%) or the Lariat snare/suture tightener (54.3%; P = .32). The remaining complications (5.7%) could not be clearly attributed to these factors or stemmed from an unknown reason.

FDA, SentreHEART Respond to Questions About Regulatory Process

 “Our analysis raises a broader issue regarding the FDA new device application 510(k) clearance protocol,” the authors write. “The FDA needs a method for reassessing the safety of a device cleared for one purpose but used frequently for a different one, as is the case for the Lariat.”

In fact, this analysis suggests that Lariat is “being used exclusively in an off-label fashion that is associated with harm in some circumstances,” Dr. Giri and colleagues observe. The pattern should be enough to trigger an internal FDA review, including possible issuance of limitations on off-label use, they say.

Via its Office of Media Affairs, the agency responded to the concerns.

The “FDA does not regulate the practice of medicine, and, as such, doctors are permitted to use a cleared or approved device in any matter they choose for their patients. When the FDA becomes aware that a device is being used in a manner that has not been shown to be safe and effective and presents new risks to patients, the agency can take appropriate action to protect the public health,” the FDA noted in an email to TCTMD, citing possibilities such as communication efforts and regulatory action—including, potentially, reclassification.

“The agency is studying information about safety risks associated with the use of the Lariat device for LAA occlusion, including our own surveillance reports and the new study published in JAMA Internal Medicine,” the response continued. “We cannot speculate about what kind of action, if any, is warranted regarding the Lariat device until we have reviewed all available scientific data.”

Additionally, it stressed, “The FDA continues to strengthen its postmarket surveillance system to identify safety issues more quickly.”

In comments provided to TCTMD, SentreHEART addressed the perceived failings of the study: “It is unfortunate that neither the company nor members of its medical advisory board were contacted by the authors to provide them with greater insight into the clinical evidence development plan in process with the FDA or the published literature on the Lariat Suture Delivery Device.”

Noting the researchers’ call for further study of Lariat specifically for LAA closure, the statement said that “SentreHEART is actively engaged with FDA and will be submitting an investigational device exemption application to FDA to conduct clinical studies of the Lariat device seeking labeling claims associated with LAA closure therapeutic indications.

“SentreHEART is committed to a rigorous clinical evidence development plan and generating prospective, long-term outcomes data,” the company said. “It is important to note that it is not unusual for device manufacturers to obtain marketing authorization for one use, and then subsequently seek additional indications for use.”

Editorial Calls for Rigorous Evaluation

In an invited commentary accompanying the paper, Paul D. Varosy, MD, of the VA Eastern Colorado Health Care System (Denver, CO), writes that the FDA approval process for medical devices is characterized by “many ‘small steps’ via the simple premarket notification, or 510(k) process, and relatively few ‘giant leaps’ via the rigorous and expensive premarket approval… process.” Most new devices undergo the 510(k) process because they are considered to represent low or intermediate risk, he notes.

Dr. Varosy reports that Lariat received 510(k) approval in 2006 as a Class II (intermediate risk) device on the basis that it was intended for “suture placement and knot tying for use in surgical applications” and was “substantially equivalent” to devices already approved for those purposes.

However, he points out, the review authors “found that the entire published literature and all the events reported to MAUDE were in association with use of the Lariat for [LAA] occlusion.”

Meanwhile, other devices specifically designed for LAA closure, including the Watchman device (Boston Scientific) and the Amplatzer Cardiac Plug (St. Jude Medical), have undergone rigorous vetting by the FDA. Watchman received approval in March 2015 only after 2 randomized trials and 3 advisory panel reviews including requests for supplemental data.

According to Dr. Varosy, the current review underscores 3 important points:

• Lariat appears to be associated with more than intermediate risk
• Use of the device in clinical practice differs from that of devices on which FDA approval was predicated
• The efficacy of Lariat for stroke risk reduction has not been evaluated

“On behalf of our patients, we should expect for the Lariat the same rigorous evaluation by randomized trials and clinical device registries that is being undertaken for other [LAA] occlusion devices,” Dr. Varosy concludes. “Until we have such data, as well as approval of the Lariat by FDA specifically for this indication, its use for [LAA] occlusion in clinical practice should be questioned.”

Risk ‘Quite Concerning’

Matthew J. Price, MD, of the Scripps Clinic (La Jolla, CA), agreed that Lariat needs evaluation appropriate to its actual use. “One of the strengths of the paper is in laying out the [discrepancy] between how the Lariat was made available for clinical use in the United States and current clinical experience,” he told TCTMD in a telephone interview.

The number of Lariat cases reported in the literature is quite small in proportion to the many thousands that have been performed in the United States, he noted, and the safety signal from the reported cases and the MAUDE data is “quite concerning.”

Dr. Price stressed that in a recent study of 154 A-fib patients who received the Lariat, the rate of pericardial effusion was 10%. Because placement of the device entails both endocardial and epicardial maneuvering, “there’s twice the potential for complications involving pericardial effusion” compared with other, single-approach devices, he explained.

Overall, he said, “the LAA devices are very exciting, but it’s hard to make heads or tails of small numbers of patients [in Lariat studies], and with the MAUDE database, we don’t know the denominator,” Dr. Price observed. “That’s the reason we do clinical trials—particularly for a prophylactic procedure when alternatives are available.”

Do Not Forget Potential Benefit

In a telephone interview with TCTMD, Gary Marcus, MD, of the University of California, San Francisco (San Francisco, CA), said the study highlights the need to understand the risks of the procedure and the predictors of adverse events. But it is also important to look at “the other side of the coin,” he said, noting that the patients most apt to benefit tend to be very sick and at high stroke risk with a contraindication for anticoagulation.

“In an ideal world, there would be a clear indication that would fit exactly what [physicians] are doing,” Dr. Marcus commented. “But there is a long history of therapies being used off label at the physician’s discretion.

“I’m somewhat conflicted,” Dr. Marcus admitted. “While SentreHEART has been supporting a registry study, I really think we need a high-quality, prospective, controlled study with separate adjudication.” He heads the steering committee for the registry study, PLACE III, which is currently on hold.

Hopefully, the current review will “motivate everyone involved to conduct” a high-quality trial and, in the meantime, “raise awareness among practitioners regarding the worst-case scenario with this device so they can counsel their patients about the risks vs the benefit.”

 Sources:
1. Chatterjee S, Herrmann HC, Wilensky RL, et al. Safety of left atrial appendage exclusion with the Lariat device: a systematic review of published reports and analytic review of the FDA MAUDE database. JAMA Intern Med. 2015;Epub ahead of print.

2. Varosy PD. Lariat—small step or giant leap [invited commentary]? JAMA Intern Med. 2015;Epub ahead of print.

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