Expanding the Role of LAAO in AFib: Clinical and Research Insights from UPMC's High-Volume Experience
July 3, 2025
Stroke remains one of the most serious complications of atrial fibrillation (AFib), largely due to thrombus formation in the left atrial appendage (LAA) during periods of ineffective atrial contraction. For decades, anticoagulation has been the first-line of defense against stroke in patients with AFib. However, the development and approval of left atrial appendage occlusion (LAAO) devices has provided a highly efficacious alternative, particularly for patients who are poor candidates for long-term anticoagulation therapy due to underlying clinical factors or patient preference.
Sandeep Jain, MD, director of Cardiac Electrophysiology and the Center for Atrial Fibrillation at the UPMC Heart and Vascular Institute, and Professor of Medicine at the University of Pittsburgh School of Medicine, and colleagues at UPMC are national and international leaders in treating and studying AFib. With more than 4,000 LAAO procedures performed across the UPMC system, the program has grown into one of the highest-volume clinical and research centers for Afib and LAAO in the US.
“Our clinical volume, expertise, and research infrastructure has allowed us to refine our approach and generate insights that not only improve our own patient outcomes but also inform how the field continues to evolve its understanding of AFib and how to achieve optimal long-term control and health outcomes," says Dr. Jain.
Understanding the Rationale for Left Atrial Appendage Occlusion
Autopsy and imaging studies have long supported the observation that a substantial proportion of AFib-related strokes originate in the LAA, with some estimates attributing up to 90% of embolic strokes in AFib due to clots forming in the LAA. Initial interventions were surgical, typically performed during concomitant cardiac procedures. These included suture ligations, excision, or the application of epicardial clips.
However, percutaneous approaches such as the Watchman FLXTM (Boston Scientific) and AmplatzerTM AmuletTM (Abbott) have now become standard practice in eligible patients. These devices, introduced under rigorous clinical protocols, are approved for use in patients who are poor candidates for long-term anticoagulation but can tolerate short-term postprocedural antithrombotic therapy
"These devices finally gave us the data we needed to understand whether occluding the appendage truly impacts stroke risk — and the answer was yes," says Dr. Jain.
Patient Selection and Expanding Indications
Candidates for LAAO typically include individuals with nonvalvular AFib who are at elevated risk for stroke, as determined by a CHA2DS2-VASc score of 3 or higher. In addition, these patients must have a contraindication or relative intolerance to long-term anticoagulation. This may include prior intracranial or gastrointestinal bleeding, high fall risk, or other comorbidities.
"It is a shared decision-making process," says Dr. Jain. "Some patients are willing to accept a small procedural risk to avoid lifelong anticoagulation, while others are not. We also have to consider the patient's overall stroke risk based on scoring systems and comorbidities."
Clinical trials are also testing the boundaries of this indication for LAAO. UPMC is a participating site in the CHAMPION and CATALYST trials, both of which are investigating whether LAAO might eventually serve as a primary alternative to anticoagulation, even in patients without the usual contraindications.
"These trials could redefine how we think about first-line stroke prevention in AFib," says Dr. Jain.
Procedural Innovations and New Imaging Modalities Combine to Expand Access to LAAO
The expansion and success of the UPMC Heart and Vascular Institute LAAO program has relied not only on procedural volume, but also on a cohesive, systemwide collaboration. From imaging to anesthesia to post-procedural care, institutional consistency has enabled refinement of shared protocols across multiple UPMC Heart and Vascular Institute sites.
With increasing procedural volume has come refinement in technique. Most LAAO procedures at UPMC are performed using transesophageal echocardiography (TEE), but intracardiac echocardiography (ICE) is emerging as a viable alternative. ICE guidance may reduce the need for general anesthesia and expand access for patients with esophageal conditions that do not permit the use of TEE.
"We are evaluating the use of ICE-guided procedures across the system. It is a small but important expansion of access for patients who otherwise would not have been eligible for LAAO," says Dr. Jain.
LAAO device selection is a patient-specific consideration, for which Dr. Jain and colleagues take into account a variety of clinical factors. Anatomic variation in the size and morphology of the LAA is important in determining whether a Watchman or Amulet device is more appropriate, though the majority of patients can usually be accommodated by one of the two devices.
"As imaging gets better and device design continues to improve, we are seeing more patients become candidates who would not have qualified a few years ago," says Dr. Jain.
Post-Procedural Management and its Role in Long-Term Outcomes
Antithrombotic management after LAAO continues to evolve. Earlier protocols required patients to remain on oral anticoagulants for at least six weeks, followed by dual antiplatelet therapy (DAPT) for six months followed by a lifelong regimen of aspirin. More recent evidence has supported the use of DAPT from the outset in some patients, reducing early bleeding risk.
"Our current practice patients is typically aspirin and clopidogrel or DOAC immediately post procedure, with a follow up transesophageal echo or CT scan at six weeks to confirm no thrombus or leak before de-escalating the patient’s use of anticoagulant therapy," says Dr. Jain.
The two major complications clinicians monitor for post-procedure after LAAO are device-related thrombus (DRT) and peri-device leaks. While small leaks can usually be managed conservatively, larger ones may call for the restarting anticoagulation or another procedure. DRT is of particular concern, as it contradicts the central aim of LAAO. Patients with DRT may require a temporary return to anticoagulation and close imaging follow-up.
"Post-procedure management is about balancing risk. We are learning to tailor follow-up based on individual risk profiles, and that is helping us improve long-term outcomes," says Dr. Jain
Institutional Research and Publications on LAAO at the UPMC Heart and Vascular Institute
The UPMC Heart and Vascular Institute has leveraged its procedural volume to contribute meaningfully to the evidence base surrounding LAAO. One part of the ongoing research effort is an internal registry of patients who have undergone a LAAO procedure. The registry allows Dr. Jain and colleagues to track outcomes, monitor complications, and identify opportunities for quality improvement and further research.
Dr. Jain and colleagues have published numerous studies based on the data in the LAAO registry. A recent retrospective study published in the Journal of Cardiovascular Electrophysiology analyzed outcomes from 350 patients undergoing combined LAAO and catheter ablation procedures across two high-volume UPMC Heart and Vascular Institute centers. The study found that the combined approach was both safe and effective, with procedural success in 99.7% of cases and no increase in major complications. The study also found low rates of device-related thrombus (1.2%) and major bleeding (2.6%), supporting the feasibility of a single-session strategy for select patients with symptomatic AFib and an indication for stroke prevention.
Another recent project compared outcomes in patients with gastrointestinal bleeding who did or did not undergo LAAO and showed reduced bleeding without an increase in stroke.
"Having a robust dataset allows us to ask questions that matter clinically, such as if combining procedures adds risk or if certain patients benefit more than others," says Dr. Jain. “The size of our registry and high-volume clinical practice allow us to find clinically impactful evidence in our patient population that we can translate into refinements in our practice.”
The UPMC Heart and Vascular Institute also routinely participates in large multicenter clinical trials and studies that are shaping clinical practice around LAAO and AFib. One recent study was the multicenter OPTION trial published in the New England Journal of Medicine, which evaluated “Left Atrial Appendage Closure After Ablation for Atrial Fibrillation.” The OPTION trial found that patients who underwent LAAO after catheter ablation versus oral anticoagulation after ablation experienced less non-procedure related bleeding events, and that LAAO was shown to be non-inferior to oral anticoagulation, “with respect to the composite of death from any cause, stroke, or systemic embolism.”
Additional studies, including the forthcoming LAAOS-4 multicenter trial that the UPMC Heart and Vascular Institute is a part of, is expected to further clarify the role of LAAO in patients with a prior history of a stroke or at a high risk of stroke.
“Traditionally, the guidance has been to keep patients with atrial fibrillation on blood thinners indefinitely to reduce stroke risk, particularly after a stroke,” says Dr. Jain. “What the LAAOS-4 trial is trying to determine is whether adding left atrial appendage occlusion on top of anticoagulation offers even greater protection. The idea is not to replace the blood thinner, but to ask whether a combined strategy is superior, especially in real-world situations where patients may miss doses, undergo procedures, or otherwise experience interruptions in anticoagulation. In that sense, the device may act as a kind of fail-safe.”
Looking Ahead: A Broader Role for LAAO
As LAAO technologies and techniques continue to advance, the boundary between traditional anticoagulation and device-based stroke prevention is becoming less distinct. In progress studies the UPMC Heart and Vascular Institute is participating in, including CATALYST and CHAMPION AF, could eventually lead to expanded approval for LAAO as a first-line option. Meanwhile, research into the interplay between AFib burden and thromboembolic risk is ongoing.
"We do not yet have a formula to quantify how AFib burden translates into stroke risk, but persistent and permanent forms likely confer more risk than paroxysmal," says Dr. Jain. "We also need better tools than CHA2DS2-VASc alone."
The UPMC Heart and Vascular Institute’s experience with more than 4,000 LAAO procedures to date offers important insights into optimizing outcomes, managing complications, and expanding access to patients for whom traditional Afib therapies may not be the best path forward.
References and Further Reading
