A soft, patient-specific left atrial appendage occluder
How combining expertise in cardiology, biomedical engineering, materials, and manufacturing led to a methodology for personalized cardiovascular implants.
While I was a graduate student at Cornell University I was fortunate to have the opportunity to spend a year at the Dalio Institute of Cardiovascular Imaging at Weill Cornell Medicine and NewYork–Presbyterian Hospital in New York City. The Dalio Institute offers the unique advantage of placing engineers, cardiologists, and radiologists side-by-side to develop solutions for cardiovascular diseases. The Left Atrial Appendage Occluder Project, one of the major thrusts of the engineering lab, was first conceived by the director of the Institute, Dr. James Min, and the PIs of the engineering lab, Professors Bobak Mosadegh and Simon Dunham. With our combined expertise in cardiology, biomedical engineering, materials, and manufacturing, we developed a soft, patient-specific occluder that we recently reported in a paper in Nature Biomedical Engineering1.
The occluder is a small, elastomeric balloon that is delivered surgically. While our ultimate goal is to make an occluder that can be delivered to the left atrial appendage (LAA) percutaneously, in this paper we focused on a clinically relevant surgical approach that allowed us to test the efficacy of the patient-specific design without the added complications of catheter delivery and deployment. This decision occurred while our engineering team was attending the 4th International Symposium on the Left Atrial Appendage in NYC—a clear example of how attending conferences in fields outside of engineering can often stimulate new thoughts on how to execute interdisciplinary research.
The left atrial appendage is a thumb-sized pocket of tissue that hangs off the left atrium in the heart. Its opening, called the ostium, is positioned just above the mitral valve and below the pulmonary veins. The ostium allows blood to flow freely from the left atrium into the appendage. Since the tip of the appendage is a dead end, the blood is forced to flow back into the left atrium upon contraction of the atria. The size and shape of the LAA can be highly variable, and therefore each of us has a unique LAA. The LAA typically does not pose an issue in healthy adult hearts, but patients with atrial fibrillation (AF) have approximately five times higher risk of stroke due to cardiac thrombi (blood clot)2, which frequently originate in their LAA (~90% of stroke-causing embolisms have been shown to originate in the LAA3). This type of thrombi formation is primarily due to the stagnant blood that occurs in the LAA for patients with AF.
To prevent stroke in patients with AF, physicians typically prescribe an oral-anticoagulant, such as warfarin. Although warfarin has demonstrated a 60% reduction in the risk of stroke4, there are many patients who cannot take blood thinners and thus need an alternative therapy. Currently, there are two modes of intervention for this subset of patients: surgical or transcatheter. Surgical methods include sewing the appendage shut, or removal of the appendage altogether. Since this is an invasive procedure, it is usually performed when the patient is having other open-chest therapies, such as valve replacement or coronary artery bypass. Transcatheter devices are typically self-expanding nitinol frames with a polymeric covering, they resemble a miniature umbrella and open within the LAA to block blood from flowing into the appendage. These devices are circular in shape and come in a limited number of sizes. Some of these devices have been shown to be non-inferior to oral-anticoagulants; however, they have several problems such as peri-device leakage or perforation of the paper-thin LAA tissue from the metal hooks used to anchor them.
To address the issues of current LAA occlusion methods, we have created a patient-specific, soft LAA occluder (Fig. 1). The patient-specificity of the occluder is achieved through the design and the material selection: the design is guided by using CT scans of the individual’s heart, and the material we chose is very soft allowing it to conform to the walls of the LAA for a snug fit upon implantation. We 3D printed molds of our design and filled them with a silicone material to fabricate very thin walled elastomeric occluders. To demonstrate the feasibility of this workflow, as well as the functionality and performance of the occluder, we implanted our device into a large animal model 2 weeks after receiving the animal’s CT scan.
The occluder works by implantation into the LAA, and then filling it with a liquid epoxy until it expands and fills the space of the appendage. After approximately 24 hours, the epoxy hardens and secures the occluder in place. Given that this device fills the space of the appendage, blood can no longer flow into the LAA, removing the risk of clot formation within the LAA. While we did not perform a chronic study, we expect after 30-45 days the atrial facing wall of the occluder to become covered with endothelial and smooth muscle cells, essentially sealing the appendage from the rest of the left atrium. Although further experiments are needed to validate the long-term performance of this occluder, we believe this work was a first step moving toward utilizing 3D printing to fabricate personalized endovascular devices.
Our paper: Robinson, S. S. et al. Patient-specific design of a soft occluder for the left atrial appendage. Nat. Biomed. Eng. 2, 8-16 (2018) doi:10.1038/s41551-017-0180-z.
1. Robinson, S. S. et al. Patient-specific design of a soft occluder for the left atrial appendage. Nat. Biomed. Eng. (2018) doi:10.1038/s41551-017-0180-z.
2. Wolf, P. A., Abbott, R. D. & Kannel, W. B.. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 22, 983–988 (1991).
3. Blackshear, J. L. & Odell, J. A. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann. Thorac. Surg. 61, 755–759 (1996).
4. Yu, C.-M. et al. Mechanical antithrombotic intervention by LAA occlusion in atrial fibrillation. Nat. Rev. Cardiol. 10, 707–722 (2013).