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Left Atrial Appendage Inversion to Prevent Stroke

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HL149478-01A1
Agency Tracking Number: R43HL149478
Amount: $365,660.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NHLBI
Solicitation Number: PA19-272
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-05-01
Award End Date (Contract End Date): 2021-10-31
Small Business Information
11107 ROSELLE ST, STE 213
San Diego, CA 92121-1206
United States
DUNS: 804419740
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (248) 808-9953
Business Contact
Phone: (858) 249-7400
Research Institution

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 1-2% of the population, and about 8% of
individuals over 80 years of age. AF has been identified as the leading cause of thromboembolic events such as
stroke. Every hour, approximately 15 patients with AF will suffer from a stroke in the US. Although prevention of
cardioembolic stroke is clinically and economically critical, traditional oral anticoagulation therapy does not have
satisfactory compliance, along with number of drawbacks. It is estimated that more than 90% of thrombi
responsible for thromboembolic events in AF form in the left atrial appendage (LAA) due to its narrow apex (blind
end), unsmooth inner surface, and irregular contraction. Excision or exclusion of the LAA with devices provides
a novel treatment strategy for preventing thromboembolic events in AF patients. There are two types of devices;
i.e., epicardial suture/clip, which closes the LAA from outside the heart, and endocardially deployed occluder,
which eliminates the dead space from the inside. The current devices have some significant disadvantages,
however, such as high cost, foreign body retention, migration, etc. The epicardial device seems to achieve better
results than endocardial device but the epicardial approach is harder to access. In this Phase I proof of concept
proposal, the objective is to partially invert the LAA endoluminally to make it resorb over time. This best of both
world approach (efficacy of clipping or resorption through an endoluminal approach) should be superior to
existing devices and methods. The hypothesis is that the inversion of the LAA will change the stress distribution
(homeostasis) in the appendage by reducing the tensile stress and even create some compressive stresses in
the tissue where a reduction in stress or compression will cause resorption as per growth-stress law. The major
deliverable is to demonstrate the safety of LAA inversion as assessed by EKG, echocardiography, histology,
cardiac biomarkers, and neurohormones to establish a new paradigm of LAA resorption as opposed to LAA
occlusion or exclusion. Our preliminary data show feasibility of this approach in a swine model where the partial
inversion of LAA was implemented surgically and endovascularly and found to eliminate the LAA dead space. In
the open-chest procedure in swine, we performed measurements at 4 weeks post-surgery, showing the inversion
of LAA is safe (no arrythmia, no hemodynamic or cardiac changes) and effective (LAA was resorbed). Compared
to current LAA closure devices, our approach leaves nothing behind (i.e., no implanted device) and hence will
be safer and much less expensive. This innovative concept along with the development of percutaneous method
for this purpose will not only provide a new treatment for the prevention of AF related embolic events but also
reduce human, social and economic burden of stroke.NARRATIVE
Approximately 1-2% of the population suffer from atrial fibrillation (AF), estimated at 12 million by 2030. These
patients are at high risk of stroke. The overall objective of this proposal is to validate the safety and efficacy of a
novel approach to prevent stroke in AF patients.

* Information listed above is at the time of submission. *

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