Abstract 2456: Chronic Amiodarone Suppresses Ventricular Tachycardia in a Mouse Model of Pediatric Cardiomyopathy
Background: Very Long-Chain Acyl-Coenzyme A Dehydrogenase (VLCAD) deficiency, an inborn error of fatty acid metabolism, causes cardiomyopathy, ventricular arrhythmias, and sudden death in children. The VLCAD knockout mouse mirrors the clinical phenotype, with cardiomyopathy and inducible ventricular tachycardia (VT). We have previously shown that acute administration of flecainide and procainamide reduce VT in VLCAD knockout mice.
Objective: To study the chronic effects of antiarrhythmic drugs in VLCAD deficiency.
Methods: Thirty-two VLCAD knockout mice underwent electrophysiology study with programmed ventricular stimulation 4 weeks after randomization to daily intraperitoneal injections of procainamide (15 mcg/g), flecainide (4 mcg/g), amiodarone (0.1 mg/g), or saline.
Results: As shown in the table⇓, all three drugs significantly prolonged RR interval, Wenckebach cycle length, and ventricular effective refractory period compared to saline-injected mice. However, only amiodarone significantly reduced VT inducibility: 89% of amiodarone-treated mice had no inducible VT, compared to 43% of saline-treated mice (P=.049, chi-square). The number of VT episodes in amiodarone-treated mice was significantly less than saline-treated mice (0.1 ± 0.3 vs. 3.3 ± 4.3 episodes, P=.039). There was a trend toward less VT in flecainide-treated mice (0.8± 2.1 episodes, P=.09 compared to saline), but no reduction with procainamide (2.2 ± 4 episodes, P=.6).
Conclusions: Chronic treatment with amiodarone significantly reduces VT in VLCAD deficient mice. Although procainamide and flecainide produced effects similar to amiodarone on heart rate, AV node conduction, and ventricular refractoriness, they were less efficacious in treating VT. These findings are in contrast to the acute effects of these drugs, and may have implications for children with cardiomyopathy due to VLCAD deficiency, as well as other fatty acid oxidation defects.