Minimally Invasive Delivery of Hydrogel-Encapsulated Amiodarone to the Epicardium Reduces Atrial Fibrillation

Circ Arrhythm Electrophysiol. 2018 May;11(5):e006408. doi: 10.1161/CIRCEP.118.006408.

Abstract

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity.

Methods: Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter.

Results: Implantation of amiodarone-containing gel significantly reduced the duration of sustained AF at 21 and 28 days; inducibility of AF was reduced 14 and 21 days post-delivery. Off-target organ drug levels in the liver, lungs, thyroid, and fat were significantly reduced in animals treated with epicardial amiodarone gel compared with systemic controls in small-animal distribution studies.

Conclusions: The pericardium is an underutilized therapeutic site and may be a new treatment strategy for AF and other cardiovascular diseases.

Keywords: amiodarone; arrhythmias, cardiac; atrial fibrillation; hydrogel, polyethylene glycol; pericardium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiodarone / administration & dosage*
  • Amiodarone / chemistry
  • Amiodarone / toxicity
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage*
  • Anti-Arrhythmia Agents / chemistry
  • Anti-Arrhythmia Agents / toxicity
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control*
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Drug Implants
  • Drug Liberation
  • Heart Rate / drug effects*
  • Hydrogels
  • Male
  • Pericardium / drug effects*
  • Pericardium / physiopathology
  • Polyethylene Glycols / chemistry*
  • Rats, Sprague-Dawley
  • Sus scrofa
  • Time Factors

Substances

  • Anti-Arrhythmia Agents
  • Drug Carriers
  • Drug Implants
  • Hydrogels
  • Polyethylene Glycols
  • Amiodarone