Local amiodarone delivery via an extracellular collagen matrix patch to reduce new-onset postoperative atrial fibrillation

Objective: Systemic amiodarone is commonly used to treat new-onset postoperative atrial fibrillation (POAF) after cardiac surgery with risk for significant toxicity. This study explored the feasibility and safety of using an extracellular collagen matrix patch (CardiaMend, or the patch), aiming to deliver therapeutically relevant concentrations of amiodarone to atrial tissues whilst mitigating the systemic adverse effects related with intravenous or oral administration of amiodarone. Methods: The patch was saturated with amiodarone hydrochloride solution (50 mg/mL, Fresenius Kabi) and implanted in ovine and rat models for pericardial and epicardial repair for up to 28 days. Amiodarone concentrations were measured in atrial tissue, lungs, liver, and plasma. Histologic analysis assessed tissue response to the patch and amiodarone application. Results: Pharmacologically relevant amiodarone concentrations were detected in atrial and ventricular tissue within 3 to 7 days, correlating with the time window for the highest incidence of POAF. Importantly, during the same time, low or undetectable drug levels were observed in the lungs, liver, and systemic circulation. Histology showed no evidence of tissue damage, fibrosis, or exacerbated inflammation associated with the patch and amiodarone application in either model. Conclusions: These findings indicate that CardiaMend can deliver therapeutically relevant concentrations of amiodarone to atrial tissues while mitigating the systemic adverse effects related with intravenous or oral administration of amiodarone. This approach could present a promising strategy for POAF prevention. Future clinical trials would be valuable to determine whether these findings translate into an effective prophylaxis for reducing the rate of new-onset POAF in cardiac surgery patients.