A Novel Combination Therapy for Post-Operative Arrhythmias

Abstract

Atrial fibrillation (AF) is a common heart rhythm disorder, effecting about 20% of cardiac surgical patients. While often benign, it leads to a prolonged hospital stay, and potentially to malignant arrhythimas. Many anti-arrhythmic drugs have been used to both prevent and treat post-operative AF and other post-operative arrhythmias; however, they have potentially harmful side-effects (e.g., hypotension, pulmonary fibrosis). Cardioversion is often the therapy of last resort to restore a perfusable rhythm. We propose a novel, innovative concept that allows for local pharmacological and electrical therapy of the heart. We have shown in animal models that such delivery increases the efficacy of the therapy and reduces side effects. Several variations of the device have been conceived and prototypes are currently being developed. The simplest version is a multi-port infusion catheter incorporated into a temporary pacing lead. Placement of the device would be trivial for surgeons, who routinely place temporary pacing leads prior to closing the chest. Removal of the device post-operatively would be equally simple. More complex iterations include an expandable wick to maintain the infused drug in a desired location. Designs may also include epicardial defibrillation capabilities, which would lower the energy required for defibrillation. To demonstrate proof of principle, cadaver and animal investigations were performed. In a fresh cadaver, a sternotomy and pericardiotomy was performed. A catheter was placed in the pericardium, and an infusion of radio-opaque contrast was administered under fluoroscopy. The majority of the contrast collected near the pulmonary veins, which are often the origin of atrial arrhythmias. To evaluate the efficacy of drugs administered into the pericardium as compared with drugs administered through the conventional route (intravenously), animal studies in swine were performed. Results demonstrated that pericardially administered metoprolol had a greater and more lasting effect on heart rate than when given intravenously. Additionally, during pericardial delivery myocardial contractility was better preserved. Only trace amounts of metoprolol were found in the circulation. Thus pericardial delivery may enhance certain therapeutic effects of drugs while limiting side effects. Currently, studies are underway to evaluate the efficacy other pharmacologic agents delivered into the pericardium. Should our animal studies continue to show promising results, we anticipate moving into clinical trials. Development and refinement of prototype delivery devices will also continue as we pursue this promising new therapy for post-operative arrhythmias.