Abstract 16562: Minimally Invasive Delivery of a Sustained Release Amiodorane Hydrogel to the Epicardium for Refractory Atrial Fibrillation
Introduction: Amiodarone is an effective medication for rhythm control in atrial fibrillation (AF) but has significant risk of toxicity in off target organs when used chronically. We developed a method to deliver amiodarone directly to the heart through the pericardial space in an extended release gel to reduce off target accumulation and toxicity.
Methods: Amiodarone-loaded liposomes were embedded within a slowly degrading polyethylene glycol hydrogel. We assayed tissue amiodarone levels in rodents given daily systemic or one time epicardial drug for 1 month (n=6 per group). We developed and tested a catheter-based system in pigs to deliver hydrogels to the surface of the heart via the pericardial space. The device creates a temporary compartment for gel localization and delivery.
Results: After 28 days, rats treated with systemic amiodarone had extensive accumulation of drug in off target organs including the thyroid (86.7 ± 20.8 μg/g) and lung (7.1 ± 1.4μg/g). In animals treated with epicardial amiodarone hydrogel, the highest off target tissue level was an order of magnitude lower than in the systemic group (thyroid, 1.9 ± 2.3 μg/g, p < 0.05). Similar cardiac drug levels were obtained in both groups (2.8 ± 0.4 v.1.2 ± 0.04 μg/g, p < 0.05). To test the feasibility and hemodynamic effects, we tested our delivery device in pigs. From the sub-xiphoid approach we placed our hydrogel delivery device over the left atrium in the pericardial space of pigs (n=3). The device formed a circular ‘fence’ and was secured to the epicardium as the ‘floor’ and pericardium as ‘ceiling’ using gentle suction. Gel components were combined outside the device in this temporary compartment and gelled as visualized by fluoroscopy. The delivery device was then unwound from around the gel and removed from the pericardial space. There were no hemodynamic effects of pericardial access nor hydrogel delivery. Filling pressures as reflected by LVEDP were normal prior to the procedure (5.0 ± 1.0 mmHg), immediately after gel placement (7.3 ± 2.3 mmHg), and after two weeks (4.0 ± 2.8 mmHg, NS).
Conclusions: Extended release amiodarone hydrogel is a translatable treatment strategy for refractory cardiac arrhythmias including AF when delivered to the epicardium using a minimally invasive delivery device.
Author Disclosures: R.D. Levit: None. P.F. Campbell: None. J. Garcia: None. J.J. Langberg: None. G. Kumar: None. E. Shin: None. L. Wang: None. Z. Marina: None. A.J. Garcia: None.
- © 2016 by American Heart Association, Inc.